Sample records for human skin cells

  1. Green tea polyphenol, (?)-epigallocatechin-3-gallate, induces toxicity in human skin cancer cells by targeting ?-catenin signaling

    SciTech Connect (OSTI)

    Singh, Tripti [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Katiyar, Santosh K., E-mail: skatiyar@uab.edu [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Birmingham Veterans Affairs Medical Center, Birmingham, AL 35233 (United States)

    2013-12-01T23:59:59.000Z

    The green tea polyphenol, (?)-epigallocatechin-3-gallate (EGCG), has been shown to have anti-carcinogenic effects in several skin tumor models, and efforts are continued to investigate the molecular targets responsible for its cytotoxic effects to cancer cells. Our recent observation that ?-catenin is upregulated in skin tumors suggested the possibility that the anti-skin carcinogenic effects of EGCG are mediated, at least in part, through its effects on ?-catenin signaling. We have found that treatment of the A431 and SCC13 human skin cancer cell lines with EGCG resulted in reduced cell viability and increased cell death and that these cytotoxic effects were associated with inactivation of ?-catenin signaling. Evidence of EGCG-induced inactivation of ?-catenin included: (i) reduced accumulation of nuclear ?-catenin; (ii) enhanced levels of casein kinase1?, reduced phosphorylation of glycogen synthase kinase-3?, and increased phosphorylation of ?-catenin on critical serine{sup 45,33/37} residues; and (iii) reduced levels of matrix metalloproteinase (MMP)-2 and MMP-9, which are down-stream targets of ?-catenin. Treatment of cells with prostaglandin E2 (PGE{sub 2}) enhanced the accumulation of ?-catenin and enhanced ?-catenin signaling. Treatment with either EGCG or an EP2 antagonist (AH6809) reduced the PGE{sub 2}-enhanced levels of cAMP, an upstream regulator of ?-catenin. Inactivation of ?-catenin by EGCG resulted in suppression of cell survival signaling proteins. siRNA knockdown of ?-catenin in A431 and SCC13 cells reduced cell viability. Collectively, these data suggest that induction of cytotoxicity in skin cancer cells by EGCG is mediated by targeting of ?-catenin signaling and that the ?-catenin signaling is upregulated by inflammatory mediators. - Highlights: • EGCG inhibits cancer cell viability through inactivation of ?-catenin signaling. • Inactivation of ?-catenin involves the downregulation of inflammatory mediators. • EGCG inactivates ?-catenin in skin cancer cells by inhibition of cAMP and PGE{sub 2}. • siRNA knockdown of ?-catenin or COX-2 reduces the viability of cancer cells.

  2. Cell motility in models of wounded human skin is improved by Gap27 despite raised glucose, insulin and IGFBP-5

    SciTech Connect (OSTI)

    Wright, Catherine S.; Berends, Rebecca F. [Department of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, 70 Cowcaddens Road, Glasgow G4 0BA (United Kingdom); Flint, David J. [Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE (United Kingdom); Martin, Patricia E.M., E-mail: Patricia.Martin@gcu.ac.uk [Department of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, 70 Cowcaddens Road, Glasgow G4 0BA (United Kingdom)

    2013-02-15T23:59:59.000Z

    Reducing Cx43 expression stimulates skin wound healing. This is mimicked in models when Cx43 function is blocked by the connexin mimetic peptide Gap27. IGF-I also stimulates wound healing with IGFBP-5 attenuating its actions. Further, the IGF-I to IGFBP-5 ratio is altered in diabetic skin, where wound closure is impaired. We investigated whether Gap27 remains effective in augmenting scrape-wound closure in human skin wound models simulating diabetes-induced changes, using culture conditions with raised glucose, insulin and IGFBP-5. Gap27 increased scrape-wound closure in normal glucose and insulin (NGI) and to a lesser extent in high glucose and insulin (HGI). IGF-I enhanced scrape-wound closure in keratinocytes whereas IGFBP-5 inhibited this response. Gap27 overcame the inhibitory effects of IGFBP-5 on IGF-I activity. Connexin-mediated communication (CMC) was reduced in HGI, despite raised Cx43, and Gap27 significantly decreased CMC in NGI and HGI. IGF-I and IGFBP-5 did not affect CMC. IGF-I increased keratinocyte proliferation in NGI, and Gap27 increased proliferation in NGI to a greater extent than in HGI. We conclude that IGF-I and Gap27 stimulate scrape-wound closure by independent mechanisms with Gap27 inhibiting Cx43 function. Gap27 can enhance wound closure in diabetic conditions, irrespective of the IGF-I:IGFBP-5 balance. - Highlights: ? Human organotypic and keratinocyte ‘diabetic’ skin models were used to demonstrate the ability of Gap27 to improve scrape-wound closure. ? Gap27 enhanced scrape-wound closure by reducing Cx43-mediated communication, whereas IGFBP-5 retarded cell migration. ? IGF-I and IGFBP-5 did not affect connexin-mediated pathways. ? Gap27 can override altered glucose, insulin, IGF-I, and IGFBP-5 in ‘diabetic’ skin models and thus has therapeutic potential.

  3. Effects of the differentiated keratinocyte phenotype on expression levels of CYP1-4 family genes in human skin cells

    SciTech Connect (OSTI)

    Du Liping [Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States); Neis, Mark M. [Department of Dermatology and Allergology, University Hospital of the RWTH, Aachen (Germany); Ladd, Patricia A. [Department of Medicine/Dermatology, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States); Lanza, Diane L. [Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112 (United States); Yost, Garold S. [Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112 (United States); Keeney, Diane S. [VA Tennessee Valley Healthcare System, Nashville, TN 37212 (United States) and Department of Medicine/Dermatology, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States) and Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States)]. E-mail: diane.keeney@vanderbilt.edu

    2006-06-01T23:59:59.000Z

    Epoxyeicosatrienoic acids produced by mouse CYP2B19 have been implicated in mechanisms regulating epidermal cornification (Ladd, P.A., Du, L., Capdevila, J.H., Mernaugh, R., Keeney, D.S., 2003. Epoxyeicosatrienoic acids activate transglutaminases in situ and induce cornification of epidermal keratinocytes. J. Biol. Chem. 278, 35184-35192). In this study, we aimed to identify CYPs that are up-regulated during keratinocyte differentiation and potentially responsible for epoxyeicosatrienoic acid formation in human skin. The cellular differentiation state of human epidermal cell cultures was manipulated to resemble the basal, spinous, and granular cell phenotypes in vivo. Changes in CYP mRNA levels were measured as a function of differentiation state for a panel of 15 CYPs that included known and putative arachidonate monooxygenases. Quantitative real-time PCR analyses showed that all of the CYPs were expressed in differentiating epidermal cell cultures and in human epidermis, with the exception of CYP2B6, which was poorly expressed in vitro. Six CYPs were strongly up-regulated at Day 6 and Day 8 of in vitro differentiation (CYP4B1, 2W1, 2C18, 3A4, 2C19, 2C9); the increase in mRNA levels ranged from 27- to 356-fold. Only CYP2U1 mRNA levels decreased (6-fold change) during cellular differentiation. Six CYPs showed little variation (<2-fold change) in mRNA levels during in vitro differentiation (CYP2S1, 2J2, 1B1, 1A1, 2E1, 2D6). No single CYP was identifiable as being a functional counterpart to CYP2B19 in mouse skin since none qualified as being mainly responsible for epidermal epoxyeicosatrienoic acid formation. Rather, the data suggest that epoxyeicosatrienoic acids in human skin are formed by several CYPs expressed in different cell layers of the epidermis. This would predict that CYP-derived eicosanoids have different functions in different epidermal cell layers.

  4. Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde

    SciTech Connect (OSTI)

    Python, Francois [Experimental Product Safety, Procter and Gamble Co., Cosmital SA, Marly (Switzerland); Goebel, Carsten [Product Safety, Human Safety Assessment, Procter and Gamble Service GmbH, Darmstadt (Germany); Aeby, Pierre [Experimental Product Safety, Procter and Gamble Co., Cosmital SA, Marly (Switzerland)], E-mail: pierre_aeby@bluewin.ch

    2009-09-15T23:59:59.000Z

    The number of studies involved in the development of in vitro skin sensitization tests has increased since the adoption of the EU 7th amendment to the cosmetics directive proposing to ban animal testing for cosmetic ingredients by 2013. Several studies have recently demonstrated that sensitizers induce a relevant up-regulation of activation markers such as CD86, CD54, IL-8 or IL-1{beta} in human myeloid cell lines (e.g., U937, MUTZ-3, THP-1) or in human peripheral blood monocyte-derived dendritic cells (PBMDCs). The present study aimed at the identification of new dendritic cell activation markers in order to further improve the in vitro evaluation of the sensitizing potential of chemicals. We have compared the gene expression profiles of PBMDCs and the human cell line MUTZ-3 after a 24-h exposure to the moderate sensitizer cinnamaldehyde. A list of 80 genes modulated in both cell types was obtained and a set of candidate marker genes was selected for further analysis. Cells were exposed to selected sensitizers and non-sensitizers for 24 h and gene expression was analyzed by quantitative real-time reverse transcriptase-polymerase chain reaction. Results indicated that PIR, TRIM16 and two Nrf2-regulated genes, CES1 and NQO1, are modulated by most sensitizers. Up-regulation of these genes could also be observed in our recently published DC-activation test with U937 cells. Due to their role in DC activation, these new genes may help to further refine the in vitro approaches for the screening of the sensitizing properties of a chemical.

  5. Coxsackie- and adenovirus receptor (CAR) is expressed in lymphatic vessels in human skin and affects lymphatic endothelial cell function in vitro

    SciTech Connect (OSTI)

    Vigl, Benjamin; Zgraggen, Claudia; Rehman, Nadia; Banziger-Tobler, Nadia E.; Detmar, Michael [Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Wolfgang-Pauli Str. 10, CH-8093 Zurich (Switzerland); Halin, Cornelia [Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Wolfgang-Pauli Str. 10, CH-8093 Zurich (Switzerland)], E-mail: cornelia.halin@pharma.ethz.ch

    2009-01-15T23:59:59.000Z

    Lymphatic vessels play an important role in tissue fluid homeostasis, intestinal fat absorption and immunosurveillance. Furthermore, they are involved in pathologic conditions, such as tumor cell metastasis and chronic inflammation. In comparison to blood vessels, the molecular phenotype of lymphatic vessels is less well characterized. Performing comparative gene expression analysis we have recently found that coxsackie- and adenovirus receptor (CAR) is significantly more highly expressed in cultured human, skin-derived lymphatic endothelial cells (LECs), as compared to blood vascular endothelial cells. Here, we have confirmed these results at the protein level, using Western blot and FACS analysis. Immunofluorescence performed on human skin confirmed that CAR is expressed at detectable levels in lymphatic vessels, but not in blood vessels. To address the functional significance of CAR expression, we modulated CAR expression levels in cultured LECs in vitro by siRNA- and vector-based transfection approaches. Functional assays performed with the transfected cells revealed that CAR is involved in distinct cellular processes in LECs, such as cell adhesion, migration, tube formation and the control of vascular permeability. In contrast, no effect of CAR on LEC proliferation was observed. Overall, our data suggest that CAR stabilizes LEC-LEC interactions in the skin and may contribute to lymphatic vessel integrity.

  6. In vitro dermal absorption of pyrethroid pesticides in human and rat skin

    SciTech Connect (OSTI)

    Hughes, Michael F., E-mail: hughes.michaelf@epa.go [Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Edwards, Brenda C. [Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States)

    2010-07-15T23:59:59.000Z

    Dermal exposure to pyrethroid pesticides can occur during manufacture and application. This study examined the in vitro dermal absorption of pyrethroids using rat and human skin. Dermatomed skin from adult male Long Evans rats or human cadavers was mounted in flow-through diffusion cells, and radiolabeled bifenthrin, deltamethrin or cis-permethrin was applied in acetone to the skin. Fractions of receptor fluid were collected every 4 h. At 24 h, the skins were washed with soap and water to remove unabsorbed chemical. The skin was then solubilized. Two additional experiments were performed after washing the skin; the first was tape-stripping the skin and the second was the collection of receptor fluid for an additional 24 h. Receptor fluid, skin washes, tape strips and skin were analyzed for radioactivity. For rat skin, the wash removed 53-71% of the dose and 26-43% remained in the skin. The cumulative percentage of the dose at 24 h in the receptor fluid ranged from 1 to 5%. For human skin, the wash removed 71-83% of the dose and 14-25% remained in the skin. The cumulative percentage of the dose at 24 h in the receptor fluid was 1-2%. Tape-stripping removed 50-56% and 79-95% of the dose in rat and human skin, respectively, after the wash. From 24-48 h, 1-3% and about 1% of the dose diffused into the receptor fluid of rat and human skin, respectively. The pyrethroids bifenthrin, deltamethrin and cis-permethrin penetrated rat and human skin following dermal application in vitro. However, a skin wash removed 50% or more of the dose from rat and human skin. Rat skin was more permeable to the pyrethroids than human skin. Of the dose in skin, 50% or more was removed by tape-stripping, suggesting that permeation of pyrethroids into viable tissue could be impeded. The percentage of the dose absorbed into the receptor fluid was considerably less than the dose in rat and human skin. Therefore, consideration of the skin type used and fractions analyzed are important when using in vitro dermal absorption data for risk assessment.

  7. Generation of insulin-producing cells from gnotobiotic porcine skin-derived stem cells

    SciTech Connect (OSTI)

    Yang, Ji Hoon; Lee, Sung Ho; Heo, Young Tae [Department of Bioscience and Biotechnology, Bio-Organ Research Center, Konkuk University, Seoul 143-701 (Korea, Republic of)] [Department of Bioscience and Biotechnology, Bio-Organ Research Center, Konkuk University, Seoul 143-701 (Korea, Republic of); Uhm, Sang Jun [Department of Animal Biotechnology, Bio-Organ Research Center, Konkuk University, Seoul 143-701 (Korea, Republic of)] [Department of Animal Biotechnology, Bio-Organ Research Center, Konkuk University, Seoul 143-701 (Korea, Republic of); Lee, Hoon Taek, E-mail: htl3675@konkuk.ac.kr [Department of Animal Biotechnology, Bio-Organ Research Center, Konkuk University, Seoul 143-701 (Korea, Republic of)

    2010-07-09T23:59:59.000Z

    A major problem in the treatment of type 1 diabetes mellitus is the limited availability of alternative sources of insulin-producing cells for islet transplantation. In this study, we investigated the effect of bone morphogenetic protein 4 (BMP-4) treatments of gnotobiotic porcine skin-derived stem cells (gSDSCs) on their reprogramming and subsequent differentiation into insulin-producing cells (IPCs). We isolated SDSCs from the ear skin of a gnotobiotic pig. During the proliferation period, the cells expressed stem-cell markers Oct-4, Sox-2, and CD90; nestin expression also increased significantly. The cells could differentiate into IPCs after treatments with activin-A, glucagon-like peptide-1 (GLP-1), and nicotinamide. After 15 days in the differentiation medium, controlled gSDSCs began expressing endocrine progenitor genes and proteins (Ngn3, Neuro-D, PDX-1, NKX2.2, NKX6.1, and insulin). The IPCs showed increased insulin synthesis after glucose stimulation. The results indicate that stem cells derived from the skin of gnotobiotic pigs can differentiate into IPCs under the appropriate conditions in vitro. Our three-stage induction protocol could be applied without genetic modification to source IPCs from stem cells in the skin of patients with diabetes for autologous transplantation.

  8. High frequency ultrasonic characterization of human skin In vivo

    E-Print Network [OSTI]

    Raju, Balasundara I. (Balasundara Iyyavu), 1972-

    2002-01-01T23:59:59.000Z

    High frequency (>20 MHz) ultrasound has numerous potential applications in dermatology because of its ability to penetrate several millimeters into the skin and provide information at a spatial resolution of tens of microns. ...

  9. A study of heat distribution in human skin: use of Infrared Thermography

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    A study of heat distribution in human skin: use of Infrared Thermography Domoina Ratovoson, Franck of this study is to be able to act quickly on body burns, to avoid propagating lesions due to heat diffusion the temperature change using an infra-red camera. Blood circulation in the veins was seen to clearly influence

  10. Real-time, Photo-realistic, Physically Based Rendering of Fine Scale Human Skin Structure

    E-Print Network [OSTI]

    Haro, Antonio

    structure samples, build models of fine scale structure production, and then render this detail usingReal-time, Photo-realistic, Physically Based Rendering of Fine Scale Human Skin Structure Antonio, which is clearly visible in close-up shots in a film or game. Methods that rely on simple texture

  11. Expression of proliferative and inflammatory markers in a full-thickness human skin equivalent following exposure to the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide

    SciTech Connect (OSTI)

    Black, Adrienne T. [Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Hayden, Patrick J. [MatTek Corporation, Ashland, MA (United States); Casillas, Robert P. [Battelle Memorial Institute, Columbus, OH (United States); Heck, Diane E. [Environmental Health Sciences, New York Medical College, Valhalla, NY (United States); Gerecke, Donald R. [Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Sinko, Patrick J. [Pharmaceutics, Rutgers University, Piscataway, NJ (United States); Laskin, Debra L. [Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Laskin, Jeffrey D., E-mail: jlaskin@eohsi.rutgers.ed [Environmental and Occupational Medicine, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ (United States)

    2010-12-01T23:59:59.000Z

    Sulfur mustard is a potent vesicant that induces inflammation, edema and blistering following dermal exposure. To assess molecular mechanisms mediating these responses, we analyzed the effects of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide, on EpiDerm-FT{sup TM}, a commercially available full-thickness human skin equivalent. CEES (100-1000 {mu}M) caused a concentration-dependent increase in pyknotic nuclei and vacuolization in basal keratinocytes; at high concentrations (300-1000 {mu}M), CEES also disrupted keratin filament architecture in the stratum corneum. This was associated with time-dependent increases in expression of proliferating cell nuclear antigen, a marker of cell proliferation, and poly(ADP-ribose) polymerase (PARP) and phosphorylated histone H2AX, markers of DNA damage. Concentration- and time-dependent increases in mRNA and protein expression of eicosanoid biosynthetic enzymes including COX-2, 5-lipoxygenase, microsomal PGE{sub 2} synthases, leukotriene (LT) A{sub 4} hydrolase and LTC{sub 4} synthase were observed in CEES-treated skin equivalents, as well as in antioxidant enzymes, glutathione S-transferases A1-2 (GSTA1-2), GSTA3 and GSTA4. These data demonstrate that CEES induces rapid cellular damage, cytotoxicity and inflammation in full-thickness skin equivalents. These effects are similar to human responses to vesicants in vivo and suggest that the full thickness skin equivalent is a useful in vitro model to characterize the biological effects of mustards and to develop potential therapeutics.

  12. A Probabilistic Model for the Human Skin Color T.S. Caetano and D.A.C. Barone

    E-Print Network [OSTI]

    Caetano, Tiberio

    ,barone}@inf.ufrgs.br _____________________________________________ Abstract We present a multivariate statistical model to represent the human skin color. In our approach part in a fully automated facial analysis system, the first important step in recognizing faces to detect faces [1-6]. However, it is a well-known fact that the majority of images acquired today

  13. Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice

    E-Print Network [OSTI]

    Chen, Qingfeng

    Adoptive transfer of human hematopoietic stem cells (HSCs) into mice lacking T, B and natural killer (NK) cells leads to development of human-blood lineage cells in the recipient mice (humanized mice). Although human B ...

  14. Reflective Terahertz Imaging for early diagnosis of skin burn severity

    E-Print Network [OSTI]

    TEWARI, PRIYAMVADA

    2013-01-01T23:59:59.000Z

    of human skin was used for hydration experiments whereby itthe human skin, was used for the hydration experiments and

  15. Demonstration of tyrosinase in the vitiligo skin of human beings by a sensitive fluorometric method as well as by 14C(U)-L-tyrosine incorporation into melanin

    SciTech Connect (OSTI)

    Husain, I.; Vijayan, E.; Ramaiah, A.; Pasricha, J.S.; Madan, N.C.

    1982-03-01T23:59:59.000Z

    Tyrosinase activity (Monophenol, dihydroxyphenylalanine: oxygen oxidoreductase EC 1.14.18.1) in vitiligo and normal epidermal homogenates of skin from human beings was measured by estimating beta 3,4-dihydroxyphenylalanine (dopa) by a highly sensitive fluorometric method described in this paper. The tyrosine activity in the vitiligo skin was about 4 to 37% of corresponding normal skin. The activity of tyrosinase in normal human skin from different individuals and from different regions of the body was in the range of 4 to 140 picomoles of beta 3,4-dihydroxyphenylalanine formed per min/mg protein of epidermal homogenate. The enzyme from vitiligo and normal skin was severely inhibited by substance(s) of low molecular weight. The enzyme exhibits a lag of about 4 hr in the absence of added beta 3,4-dihydroxyphenylalanine and 1 hr in presence of 5 microM dopa. Tyrosinase from the normal and vitiligo skin was inhibited by excess concentration of tyrosine. The homogenates from vitiligo skin could synthesize melanin from C14(U)-L-Tyrosine. The rate of tyrosine incorporation into melanin by the epidermal homogenates is increased by 3,4-dihydroxyphenylalanine (dopa) disproportionate to its effect on tyrosinase activity. Based on the data presented in this paper it is concluded that melanocytes are present in the vitiligo skin. A tentative hypothesis is put forward to explain the lack of melanin synthesis by the vitiligo skin under in vivo conditions, although melanocytes are present.

  16. Thermal Modeling and Experimental Validation of Human Hair and Skin Heated by Broadband Light

    E-Print Network [OSTI]

    Aguilar, Guillermo

    distribution within the hair follicle is highly non-uniform: the minimum temperature occurs at the follicle Sun, PhD,1 Alex Chaney,1 Robert Anderson, PhD,2 and Guillermo Aguilar, PhD 1 * 1 Department:(a)determinetheoveralleffectofPPxonskinhumidi- tyandassociatedskinopticalproperties,and;(b)developaPT numerical model to study the spatial and temporal hair and skin temperature

  17. Osmotic water permeability of human red cells

    SciTech Connect (OSTI)

    Terwilliger, T.C.; Solomon, A.K.

    1981-05-01T23:59:59.000Z

    The osmotic water permeability of human red cells has been reexamined with a stopped-flow device and a new perturbation technique. Small osmotic gradients are used to minimize the systematic error caused by nonlinearities in the relationship between cell volume and light scattering. Corrections are then made for residual systematic error. Our results show that the hydraulic conductivity, Lp, is essentially independent of the direction of water flow and of osmolality in the range 184-365 mosM. the mean value of Lp obtained obtained was 1.8 +/- 0.1 (SEM) X 10-11 cm3 dyne -1 s-1.

  18. Generation of Human Embryonic Stem Cell-Derived Mesoderm and Cardiac Cells

    E-Print Network [OSTI]

    Zandstra, Peter W.

    ARTICLE Generation of Human Embryonic Stem Cell-Derived Mesoderm and Cardiac Cells Using Size InterScience (www.interscience.wiley.com). DOI 10.1002/bit.22065 ABSTRACT: The ability to generate human for the differentiation of pluripotent cells such as human embryonic stem cells (hESC) rely on the generation

  19. Isolation of stem cells from adult telogen skin Elizabeth Deschene Greco Lab

    E-Print Network [OSTI]

    Greco, Valentina

    piece of skin of 1 inch wide by 2 inches long. Take a small piece for OCT embedding if necessary. · Put solution: Our SIGMA stock is 200 mg/ml. I then dilute this stock 1:80 in 37 pre-warmed HBBS media and put

  20. Periodic patterning stem cells and induction of skin appendages: p-ERK-dependent mes-enchymal condensation is coupled with Turing mechanism to convert stripes to spots

    E-Print Network [OSTI]

    Maini, Philip K.

    ABSTRACTS 931 Periodic patterning stem cells and induction of skin appendages: p-ERK-dependent mes patterns remains unknown. Using the feather model, here we show ERK activity-dependent mesenchymal cell chemotaxis toward initial peaks is essential for completing pattern formation. Adding ERK inhibitors produced

  1. Activating Mutations of NOTCH1 in Human T Cell Acute

    E-Print Network [OSTI]

    Activating Mutations of NOTCH1 in Human T Cell Acute Lymphoblastic Leukemia Andrew P. Weng,1 Stephen C. Blacklow,1 A. Thomas Look,2 Jon C. Aster1 - Very rare cases of human T cell acute lymphoblastic leukemia (T-ALL) harbor chromosomal translocations that involve NOTCH1, a gene encoding a trans- membrane

  2. Skin flicks

    E-Print Network [OSTI]

    Orth, Margaret A. (Margaret Ann), 1964-

    1993-01-01T23:59:59.000Z

    The written and artistic part of this thesis are both separated into the two categories of "SKIN" and "FLICKS". The Artistic part of my thesis consists of five artificial skins made on my body, and a series of video tapes ...

  3. Comparison of blood flow and cell function in ischemic skin flaps

    SciTech Connect (OSTI)

    Bean, D.; Rees, R.S.; O'Leary, J.P.; Lynch, J.B.

    1984-07-01T23:59:59.000Z

    Cellular function and blood flow in acute, steroid-treated, and surgically delayed random skin flaps have been examined. In these studies, the period following flap elevation could be divided into early (0-2 hr), intermediate (4-6 hr), and late (12 hr) periods of ischemia, based on the cutaneous blood flow and cellular function measured by thallium-201 uptake. There was a close correlation between blood flow and cellular function during the early period of ischemia which became worse with time. Blood flow studies demonstrated a significant difference between the early and intermediate periods of ischemia which was abolished by surgical delay. Improvement in cellular function was accomplished by improved blood flow in the surgically delayed flaps, while steroid-treated flaps enhanced cellular metabolism by another mechanism. Cellular function approximated blood flow during the early and immediate period of ischemia. Steroids may augment cellular function without improving blood flow, while surgical delay improves cellular function by improving blood flow.

  4. Human papillomavirus 16 E5 induces bi-nucleated cell formation by cell-cell fusion

    SciTech Connect (OSTI)

    Hu Lulin; Plafker, Kendra [Department of Cell Biology, University of Oklahoma (United States); Vorozhko, Valeriya [Department of Cell Biology, University of Oklahoma (United States); Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation (United States); Zuna, Rosemary E. [Department of Pathology, University of Oklahoma HSC (United States); Hanigan, Marie H. [Department of Cell Biology, University of Oklahoma (United States); Gorbsky, Gary J. [Department of Cell Biology, University of Oklahoma (United States); Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation (United States); Plafker, Scott M. [Department of Cell Biology, University of Oklahoma (United States); Angeletti, Peter C. [Nebraska Center for Virology (United States); Ceresa, Brian P. [Department of Cell Biology, University of Oklahoma (United States)], E-mail: brian-ceresa@oushc.edu

    2009-02-05T23:59:59.000Z

    Human papillomaviruses (HPV) 16 is a DNA virus encoding three oncogenes - E5, E6, and E7. The E6 and E7 proteins have well-established roles as inhibitors of tumor suppression, but the contribution of E5 to malignant transformation is controversial. Using spontaneously immortalized human keratinocytes (HaCaT cells), we demonstrate that expression of HPV16 E5 is necessary and sufficient for the formation of bi-nucleated cells, a common characteristic of precancerous cervical lesions. Expression of E5 from non-carcinogenic HPV6b does not produce bi-nucleate cells. Video microscopy and biochemical analyses reveal that bi-nucleates arise through cell-cell fusion. Although most E5-induced bi-nucleates fail to propagate, co-expression of HPV16 E6/E7 enhances the proliferation of these cells. Expression of HPV16 E6/E7 also increases bi-nucleated cell colony formation. These findings identify a new role for HPV16 E5 and support a model in which complementary roles of the HPV16 oncogenes lead to the induction of carcinogenesis.

  5. Reactive oxygen species mediate arsenic induced cell transformation and tumorigenesis through Wnt/{beta}-catenin pathway in human colorectal adenocarcinoma DLD1 cells

    SciTech Connect (OSTI)

    Zhang Zhuo [Department of Preventive Medicine and Environmental Health, University of Kentucky, 121 Washington Avenue, Lexington, KY 40536 (United States); Wang Xin; Cheng Senping; Sun Lijuan; Son, Young-Ok [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Yao Hua [Department of Stomatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003 (China); Li Wenqi [Department of Preventive Medicine and Environmental Health, University of Kentucky, 121 Washington Avenue, Lexington, KY 40536 (United States); Budhraja, Amit [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Li Li [Department of Family Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Shelton, Brent J.; Tucker, Thomas [Markey Cancer Control Program, University of Kentucky, 2365 Harrodsburg Rd, Lexington, KY 40504 (United States); Arnold, Susanne M. [Markey Cancer Center, University of Kentucky, 800 Rose street, Lexington, KY 40536 (United States); Shi Xianglin, E-mail: Xianglin.sh@uky.edu [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States)

    2011-10-15T23:59:59.000Z

    Long term exposure to arsenic can increase incidence of human cancers, such as skin, lung, and colon rectum. The mechanism of arsenic induced carcinogenesis is still unclear. It is generally believed that reactive oxygen species (ROS) may play an important role in this process. In the present study, we investigate the possible linkage between ROS, {beta}-catenin and arsenic induced transformation and tumorigenesis in human colorectal adenocarcinoma cell line, DLD1 cells. Our results show that arsenic was able to activate p47{sup phox} and p67{sup phox}, two key proteins for activation of NADPH oxidase. Arsenic was also able to generate ROS in DLD1 cells. Arsenic increased {beta}-catenin expression level and its promoter activity. ROS played a major role in arsenic-induced {beta}-catenin activation. Treatment of DLD1 cells by arsenic enhanced both transformation and tumorigenesis of these cells. The tumor volumes of arsenic treated group were much larger than those without arsenic treatment. Addition of either superoxide dismutase (SOD) or catalase reduced arsenic induced cell transformation and tumor formation. The results indicate that ROS are involved in arsenic induced cell transformation and tumor formation possible through Wnt/{beta}-catenin pathway in human colorectal adenocarcinoma cell line DLD1 cells. - Highlights: > Arsenic activates NADPH oxidase and increases reactive oxygen species generation in DLD1 cells. > Arsenic increases {beta}-catenin expression. > Inhibition of ROS induced by arsenic reduce {beta}-catenin expression. > Arsenic increases cell transformation in DLD1 cells and tumorigenesis in nude mice. > Blockage of ROS decrease cell transformation and tumorigenesis induced by arsenic.

  6. Expansion of Human Cord Blood Hematopoietic Stem Cells for Transplantation

    E-Print Network [OSTI]

    Chou, Song

    A recent Science paper reported a purine derivative that expands human cord blood hematopoietic stem cells in culture ( Boitano et al., 2010) by antagonizing the aryl hydrocarbon receptor. Major problems need to be overcome ...

  7. Low-dose radiation impacts skin sensitivity | EMSL

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Low-dose radiation impacts skin sensitivity Low-dose radiation impacts skin sensitivity Released: April 06, 2015 Systems approach suggests alterations in stability of cells and...

  8. Genome-wide In-silico Identification of Transcriptional Regulators Controlling Cell Cycle in Human Cells

    E-Print Network [OSTI]

    Shamir, Ron

    - 1 - Genome-wide In-silico Identification of Transcriptional Regulators Controlling Cell Cycle-3-6409760 Fax: 972-3-6407471 e-mail: yossih@post.tau.ac.il Running title: Transcriptional regulation of human cell cycle Key words: Transcriptional regulation, cell cycle, functional genomics. #12;- 2 - Abstract

  9. Regulation of apoptosis in human cancer cells

    E-Print Network [OSTI]

    Lloyd, S. Julie-Ann (Simone Julie-Ann)

    2005-01-01T23:59:59.000Z

    Nitric oxide is postulated to protect cancer cells from the death-inducing effects of tumour necrosis factor alpha by S-nitrosating the active site cysteines, inhibiting cleavage of caspase-9. We aimed to test this hypothesis ...

  10. Three Human Cell Types Respond to Multi-Walled Carbon Nanotubes...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Human Cell Types Respond to Multi-Walled Carbon Nanotubes and Titanium Dioxide Nanobelts with Cell-Specific Transcriptomic Three Human Cell Types Respond to Multi-Walled Carbon...

  11. Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells

    SciTech Connect (OSTI)

    Timper, Katharina [Department of Research, University Hospital, Basel (Switzerland); Seboek, Dalma [Department of Research, University Hospital, Basel (Switzerland); Eberhardt, Michael [Department of Research, University Hospital, Basel (Switzerland); Linscheid, Philippe [Department of Research, University Hospital, Basel (Switzerland); Christ-Crain, Mirjam [Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital, Basel (Switzerland); Keller, Ulrich [Department of Research, University Hospital, Basel (Switzerland); Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital, Basel (Switzerland); Mueller, Beat [Department of Research, University Hospital, Basel (Switzerland); Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital, Basel (Switzerland); Zulewski, Henryk [Department of Research, University Hospital, Basel (Switzerland) and Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital, Basel (Switzerland)]. E-mail: henryk.zulewski@unibas.ch

    2006-03-24T23:59:59.000Z

    Mesenchymal stem cells (MSC) from mouse bone marrow were shown to adopt a pancreatic endocrine phenotype in vitro and to reverse diabetes in an animal model. MSC from human bone marrow and adipose tissue represent very similar cell populations with comparable phenotypes. Adipose tissue is abundant and easily accessible and could thus also harbor cells with the potential to differentiate in insulin producing cells. We isolated human adipose tissue-derived MSC from four healthy donors. During the proliferation period, the cells expressed the stem cell markers nestin, ABCG2, SCF, Thy-1 as well as the pancreatic endocrine transcription factor Isl-1. The cells were induced to differentiate into a pancreatic endocrine phenotype by defined culture conditions within 3 days. Using quantitative PCR a down-regulation of ABCG2 and up-regulation of pancreatic developmental transcription factors Isl-1, Ipf-1, and Ngn3 were observed together with induction of the islet hormones insulin, glucagon, and somatostatin.

  12. Evaluation of nitroimidazole hypoxic cell radiosensitizers in a human tumor cell line high in intracellular glutathione

    SciTech Connect (OSTI)

    DeGraff, W.G.; Russo, A.; Gamson, J.; Mitchell, J.B.

    1989-04-01T23:59:59.000Z

    Five nitroimidazole hypoxic cell radiosensitizers were evaluated in a human lung adenocarcinoma cell line (A549) whose GSH level was 8-fold higher than Chinese hamster V79 cells. One millimolar concentrations of Misonidazole (MISO), SR-2508, RSU-1164, RSU-1172, and Ro-03-8799 sensitized hypoxic A549 cells to radiation, with Ro-03-8799 giving the highest sensitizer enhancement ration (SER) (2.3). However, MISO, SR-2508 and Ro-03-8799 were less effective in this cell line than in V79 cells, presumably due to higher GSH content of the A549 cells. Increased hypoxic radiosensitization was seen with 0.1 mM Ro-03-8799 after GSH depletion by BSO as compared to 0.1 mM Ro-03-8799 alone (SER-1.8 vs 1.3). The combination of GSH depletion and 0.1 mM Ro-03-8799 was considerably more toxic than 0.1 mM or 1.0 mM Ro-03-8799 alone. This sensitivity was much greater than has been observed for SR-2508. These data show that Ro-03-8799 was the most efficient hypoxic cell radiosensitizer in a human tumor cell line considerably higher in GSH than the rodent cell lines often used in hypoxic radiosensitization studies. Thus, Ro-03-8799 may be a more effective hypoxic cell sensitizer in human tumors that are high in GSH.

  13. Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells

    SciTech Connect (OSTI)

    Person, Rachel J.; Tokar, Erik J.; Xu, Yuanyuan; Orihuela, Ruben; Ngalame, Ntube N. Olive; Waalkes, Michael P., E-mail: waalkes@niehs.nih.gov

    2013-12-01T23:59:59.000Z

    Cadmium is a known human lung carcinogen. Here, we attempt to develop an in vitro model of cadmium-induced human lung carcinogenesis by chronically exposing the peripheral lung epithelia cell line, HPL-1D, to a low level of cadmium. Cells were chronically exposed to 5 ?M cadmium, a noncytotoxic level, and monitored for acquired cancer characteristics. By 20 weeks of continuous cadmium exposure, these chronic cadmium treated lung (CCT-LC) cells showed marked increases in secreted MMP-2 activity (3.5-fold), invasion (3.4-fold), and colony formation in soft agar (2-fold). CCT-LC cells were hyperproliferative, grew well in serum-free media, and overexpressed cyclin D1. The CCT-LC cells also showed decreased expression of the tumor suppressor genes p16 and SLC38A3 at the protein levels. Also consistent with an acquired cancer cell phenotype, CCT-LC cells showed increased expression of the oncoproteins K-RAS and N-RAS as well as the epithelial-to-mesenchymal transition marker protein Vimentin. Metallothionein (MT) expression is increased by cadmium, and is typically overexpressed in human lung cancers. The major MT isoforms, MT-1A and MT-2A were elevated in CCT-LC cells. Oxidant adaptive response genes HO-1 and HIF-1A were also activated in CCT-LC cells. Expression of the metal transport genes ZNT-1, ZNT-5, and ZIP-8 increased in CCT-LC cells culminating in reduced cadmium accumulation, suggesting adaptation to the metal. Overall, these data suggest that exposure of human lung epithelial cells to cadmium causes acquisition of cancer cell characteristics. Furthermore, transformation occurs despite the cell's ability to adapt to chronic cadmium exposure. - Highlights: • Chronic cadmium exposure induces cancer cell characteristics in human lung cells. • This provides an in vitro model of cadmium-induced human lung cell transformation. • This occurred with general and lung specific changes typical for cancer cells. • These findings add insight to the relationship between cadmium and lung cancer.

  14. Teroxirone inhibited growth of human non-small cell lung cancer cells by activating p53

    SciTech Connect (OSTI)

    Wang, Jing-Ping; Lin, Kai-Han; Liu, Chun-Yen; Yu, Ya-Chu; Wu, Pei-Tsun [Department of Life Science, National Taiwan Normal University, Taipei, Taiwan (China); Chiu, Chien-Chih [Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Su, Chun-Li [Department of Human Development and Family Studies, National Taiwan Normal University, Taipei, Taiwan (China); Chen, Kwun-Min [Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan (China); Fang, Kang, E-mail: kangfang@ntnu.edu.tw [Department of Life Science, National Taiwan Normal University, Taipei, Taiwan (China)

    2013-11-15T23:59:59.000Z

    In this work, we demonstrated that the growth of human non-small-cell-lung-cancer cells H460 and A549 cells can be inhibited by low concentrations of an epoxide derivative, teroxirone, in both in vitro and in vivo models. The cytotoxicity was mediated by apoptotic cell death through DNA damage. The onset of ultimate apoptosis is dependent on the status of p53. Teroxirone caused transient elevation of p53 that activates downstream p21 and procaspase-3 cleavage. The presence of caspase-3 inhibitor reverted apoptotic phenotype. Furthermore, we showed the cytotoxicity of teroxirone in H1299 cells with stable ectopic expression of p53, but not those of mutant p53. A siRNA-mediated knockdown of p53 expression attenuated drug sensitivity. The in vivo experiments demonstrated that teroxirone suppressed growth of xenograft tumors in nude mice. Being a potential therapeutic agent by restraining cell growth through apoptotic death at low concentrations, teroxirone provides a feasible perspective in reversing tumorigenic phenotype of human lung cancer cells. - Highlights: • Teroxirone repressed tumor cell growth in nude mice of human lung cancer cells. • The apoptotic cell death reverted by caspase-3 inhibitor is related to p53 status. • Teroxirone provides a good candidate for lung cancer treatment.

  15. Working with Human Cells in Animals This cubicle is currently housing _____________ (animal species) that have been injected with human cell

    E-Print Network [OSTI]

    Cui, Yan

    ) and Animal Biosafety Level 2 (ABSL2). Personnel working on the protocols must be trained in the hazards) that have been injected with human cell lines. The protocol will be conducted at Biosafety Level 2 (BSL2 of as biological waste. After the completion of these procedures, personnel will remove all PPE and must wash his

  16. Uptake and cytotoxicity of chitosan nanoparticles in human liver cells

    SciTech Connect (OSTI)

    Loh, Jing Wen [Laboratory for Drug Delivery, Pharmacy, University of Western Australia, 35 Stirling Hwy, Crawley, 6009 (Australia); Yeoh, George [School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, 35 Stirling Hwy, Crawley, 6009 (Australia); Centre for Medical Research, Western Australian Institute for Medical Research, Nedlands, WA 6009 (Australia); Saunders, Martin [Centre for Microscopy, Characterisation and Analysis, University of Western Australia, 35 Stirling Hwy, Crawley, 6009 (Australia); Lim, Lee-Yong, E-mail: limly@cyllene.uwa.edu.a [Laboratory for Drug Delivery, Pharmacy, University of Western Australia, 35 Stirling Hwy, Crawley, 6009 (Australia); School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, 35 Stirling Hwy, Crawley, 6009 (Australia)

    2010-12-01T23:59:59.000Z

    Despite extensive research into the biomedical and pharmaceutical applications of nanoparticles, and the liver being the main detoxifying organ in the human body, there are limited studies which delineate the hepatotoxicity of nanoparticles. This paper reports on the biological interactions between liver cells and chitosan nanoparticles, which have been widely recognised as biocompatible. Using the MTT assay, human liver cells were shown to tolerate up to 4 h of exposure to 0.5% w/v of chitosan nanoparticles (18 {+-} 1 nm, 7.5 {+-} 1.0 mV in culture medium). At nanoparticle concentrations above 0.5% w/v, cell membrane integrity was compromised as evidenced by leakage of alanine transaminase into the extracellular milieu, and there was a dose-dependent increase in CYP3A4 enzyme activity. Uptake of chitosan nanoparticles into the cell nucleus was observed by confocal microscopic analysis after 4 h exposure with 1% w/v of chitosan nanoparticles. Electron micrographs further suggest necrotic or autophagic cell death, possibly caused by cell membrane damage and resultant enzyme leakage.

  17. Trichodermin induces cell apoptosis through mitochondrial dysfunction and endoplasmic reticulum stress in human chondrosarcoma cells

    SciTech Connect (OSTI)

    Su, Chen-Ming [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Wang, Shih-Wei [Department of Medicine, Mackay Medical College, New Taipei City, Taiwan (China); Lee, Tzong-Huei [Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan (China); Tzeng, Wen-Pei [Graduate Institute of Sports and Health, National Changhua University of Education, Changhua, Taiwan (China); Hsiao, Che-Jen [School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Liu, Shih-Chia [Department of Orthopaedics, Mackay Memorial Hospital, Taipei, Taiwan (China); Tang, Chih-Hsin, E-mail: chtang@mail.cmu.edu.tw [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan (China); Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan (China)

    2013-10-15T23:59:59.000Z

    Chondrosarcoma is the second most common primary bone tumor, and it responds poorly to both chemotherapy and radiation treatment. Nalanthamala psidii was described originally as Myxosporium in 1926. This is the first study to investigate the anti-tumor activity of trichodermin (trichothec-9-en-4-ol, 12,13-epoxy-, acetate), an endophytic fungal metabolite from N. psidii against human chondrosarcoma cells. We demonstrated that trichodermin induced cell apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353 cells) instead of primary chondrocytes. In addition, trichodermin triggered endoplasmic reticulum (ER) stress protein levels of IRE1, p-PERK, GRP78, and GRP94, which were characterized by changes in cytosolic calcium levels. Furthermore, trichodermin induced the upregulation of Bax and Bid, the downregulation of Bcl-2, and the dysfunction of mitochondria, which released cytochrome c and activated caspase-3 in human chondrosarcoma. In addition, animal experiments illustrated reduced tumor volume, which led to an increased number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells and an increased level of cleaved PARP protein following trichodermin treatment. Together, this study demonstrates that trichodermin is a novel anti-tumor agent against human chondrosarcoma cells both in vitro and in vivo via mitochondrial dysfunction and ER stress. - Highlights: • Trichodermin induces chondrosarcoma apoptosis. • ER stress is involved in trichodermin-induced cell death. • Trichodermin induces chondrosarcoma death in vivo.

  18. Raman Spectroscopy of DNA Packaging in Individual Human Sperm Cells distinguishes Normal from Abnormal Cells

    SciTech Connect (OSTI)

    Huser, T; Orme, C; Hollars, C; Corzett, M; Balhorn, R

    2009-03-09T23:59:59.000Z

    Healthy human males produce sperm cells of which about 25-40% have abnormal head shapes. Increases in the percentage of sperm exhibiting aberrant sperm head morphologies have been correlated with male infertility, and biochemical studies of pooled sperm have suggested that sperm with abnormal shape may contain DNA that has not been properly repackaged by protamine during spermatid development. We have used micro-Raman spectroscopy to obtain Raman spectra from individual human sperm cells and examined how differences in the Raman spectra of sperm chromatin correlate with cell shape. We show that Raman spectra of individual sperm cells contain vibrational marker modes that can be used to assess the efficiency of DNA-packaging for each cell. Raman spectra obtained from sperm cells with normal shape provide evidence that DNA in these sperm is very efficiently packaged. We find, however, that the relative protein content per cell and DNA packaging efficiencies are distributed over a relatively wide range for sperm cells with both normal and abnormal shape. These findings indicate that single cell Raman spectroscopy should be a valuable tool in assessing the quality of sperm cells for in-vitro fertilization.

  19. Sickle erythrocytes inhibit human endothelial cell DNA synthesis

    SciTech Connect (OSTI)

    Weinstein, R.; Zhou, M.A.; Bartlett-Pandite, A.; Wenc, K. (St. Elizabeth's Hospital of Boston, MA (USA))

    1990-11-15T23:59:59.000Z

    Patients with sickle cell anemia experience severe vascular occlusive phenomena including acute pain crisis and cerebral infarction. Obstruction occurs at both the microvascular and the arterial level, and the clinical presentation of vascular events is heterogeneous, suggesting a complex etiology. Interaction between sickle erythrocytes and the endothelium may contribute to vascular occlusion due to alteration of endothelial function. To investigate this hypothesis, human vascular endothelial cells were overlaid with sickle or normal erythrocytes and stimulated to synthesize DNA. The erythrocytes were sedimented onto replicate monolayers by centrifugation for 10 minutes at 17 g to insure contact with the endothelial cells. Incorporation of 3H-thymidine into endothelial cell DNA was markedly inhibited during contact with sickle erythrocytes. This inhibitory effect was enhanced more than twofold when autologous sickle plasma was present during endothelial cell labeling. Normal erythrocytes, with or without autologous plasma, had a modest effect on endothelial cell DNA synthesis. When sickle erythrocytes in autologous sickle plasma were applied to endothelial monolayers for 1 minute, 10 minutes, or 1 hour and then removed, subsequent DNA synthesis by the endothelial cells was inhibited by 30% to 40%. Although adherence of sickle erythrocytes to the endothelial monolayers was observed under these experimental conditions, the effect of sickle erythrocytes on endothelial DNA synthesis occurred in the absence of significant adherence. Hence, human endothelial cell DNA synthesis is partially inhibited by contact with sickle erythrocytes. The inhibitory effect of sickle erythrocytes occurs during a brief (1 minute) contact with the endothelial monolayers, and persists for at least 6 hours of 3H-thymidine labeling.

  20. Photosensitization of human leukemic cells by anthracenedione antitumor agents

    SciTech Connect (OSTI)

    Hartley, J.A.; Forrow, S.M.; Souhami, R.L.; Reszka, K.; Lown, J.W. (University College and Middlesex School of Medicine, London (England))

    1990-03-15T23:59:59.000Z

    1,4-Diamino-substituted anthraquinone antitumor agents (mitoxantrone and ametantrone) and structurally related 1,5- and 1,8-diamino-substituted compounds (AM1 and AM2) were tested for their ability to photosensitize human leukemic cells in culture. Viability was measured using the 3,4,5-dimethylthiazol-2,5-diphenyl tetrazolium bromide assay, and DNA and membrane damage were assessed. Following a 1-h exposure to AM2, a dose of drug required to give 50% loss of cell viability (53 microM) was obtained in the dark, which was reduced to approximately 2.4 microM following illumination for 2 min (lambda greater than 475 nm), a dose of light that was completely nontoxic to the cells in the absence of drug. A shift in the cell viability curve was also observed for AM1 but, under identical conditions, the dose modification was only 8.9. In contrast, neither ametantrone nor mitoxantrone gave a decreased viability upon illumination. DNA single-strand breaks as measured by alkaline elution correlated with cell viability. Frank DNA single-strand breaks were produced by AM2 and light, suggesting the production of free radicals. The strand breaks produced by AM2 in the dark and by mitoxantrone (with or without illumination) were protein concealed. No evidence of photo-induced membrane damage, as determined by transport of the model amino acid cycloleucine, could be observed even at supralethal doses.

  1. Vorinostat, an HDAC inhibitor attenuates epidermoid squamous cell carcinoma growth by dampening mTOR signaling pathway in a human xenograft murine model

    SciTech Connect (OSTI)

    Kurundkar, Deepali; Srivastava, Ritesh K.; Chaudhary, Sandeep C. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States)] [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States); Ballestas, Mary E. [Department of Pediatrics Infectious Disease, Children's of Alabama, School of Medicine, University of Alabama at Birmingham, AL (United States)] [Department of Pediatrics Infectious Disease, Children's of Alabama, School of Medicine, University of Alabama at Birmingham, AL (United States); Kopelovich, Levy [Division of Cancer Prevention, National Cancer Institute, 6130 Executive Blvd., Suite 2114, Bethesda, MD 20892 (United States)] [Division of Cancer Prevention, National Cancer Institute, 6130 Executive Blvd., Suite 2114, Bethesda, MD 20892 (United States); Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States)] [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States)] [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States)

    2013-01-15T23:59:59.000Z

    Histone deacetylase (HDAC) inhibitors are potent anticancer agents and show efficacy against various human neoplasms. Vorinostat is a potent HDAC inhibitor and has shown potential to inhibit growth of human xenograft tumors. However, its effect on the growth of skin neoplasm remains undefined. In this study, we show that vorinostat (2 ?M) reduced expression of HDAC1, 2, 3, and 7 in epidermoid carcinoma A431 cells. Consistently, it increased acetylation of histone H3 and p53. Vorinostat (100 mg/kg body weight, IP) treatment reduced human xenograft tumor growth in highly immunosuppressed nu/nu mice. Histologically, the vorinostat-treated tumor showed features of well-differentiation with large necrotic areas. Based on proliferating cell nuclear antigen (PCNA) staining and expression of cyclins D1, D2, E, and A, vorinostat seems to impair proliferation by down-regulating the expression of these proteins. However, it also induced apoptosis. The mechanism by which vorinostat blocks proliferation and makes tumor cells prone to apoptosis, involved inhibition of mTOR signaling which was accompanied by reduction in cell survival AKT and extracellular-signal regulated kinase (ERK) signaling pathways. Our data provide a novel mechanism-based therapeutic intervention for cutaneous squamous cell carcinoma (SCC). Vorinostat may be utilized to cure skin neoplasms in organ transplant recipient (OTR). These patients have high morbidity and surgical removal of these lesions which frequently develop in these patients, is difficult. -- Highlights: ? Vorinostat reduces SCC growth in a xenograft murine model. ? Vorinostat dampens proliferation and induces apoptosis in tumor cells. ? Diminution in mTOR, Akt and ERK signaling underlies inhibition in proliferation. ? Vorinostat by inhibiting HDACs inhibits epithelial–mesenchymal transition.

  2. Cell lines for the production of monoclonal antibodies to human glycophorin A

    DOE Patents [OSTI]

    Bigbee, William L. (Livermore, CA); Fong, Stella S. N. (Del Mar, CA); Jensen, Ronald H. (Livermore, CA); Vanderlaan, Martin (San Ramon, CA); Langlois, Richard G. (Livermore, CA)

    1988-01-01T23:59:59.000Z

    Cloned mouse hybridoma cell lines have been established which continuously produce antibodies that differentiate between the M and N forms of human glycophorin A. These antibodies have potential application as human blood group reagents, as markers for terminally differentiated erythroid cells and as immunofluorescent labels of somatically variant human erythrocytes.

  3. Induction of apoptotic death and retardation of neuronal differentiation of human neural stem cells by sodium arsenite treatment

    SciTech Connect (OSTI)

    Ivanov, Vladimir N., E-mail: vni3@columbia.edu [Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, NY 10032 (United States); Hei, Tom K. [Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, NY 10032 (United States)

    2013-04-01T23:59:59.000Z

    Chronic arsenic toxicity is a global health problem that affects more than 100 million people worldwide. Long-term health effects of inorganic sodium arsenite in drinking water may result in skin, lung and liver cancers and in severe neurological abnormalities. We investigated in the present study whether sodium arsenite affects signaling pathways that control cell survival, proliferation and neuronal differentiation of human neural stem cells (NSC). We demonstrated that the critical signaling pathway, which was suppressed by sodium arsenite in NSC, was the protective PI3K–AKT pathway. Sodium arsenite (2–4 ?M) also caused down-regulation of Nanog, one of the key transcription factors that control pluripotency and self-renewal of stem cells. Mitochondrial damage and cytochrome-c release induced by sodium arsenite exposure was followed by initiation of the mitochondrial apoptotic pathway in NSC. Beside caspase-9 and caspase-3 inhibitors, suppression of JNK activity decreased levels of arsenite-induced apoptosis in NSC. Neuronal differentiation of NSC was substantially inhibited by sodium arsenite exposure. Overactivation of JNK1 and ERK1/2 and down-regulation of PI3K–AKT activity induced by sodium arsenite were critical factors that strongly affected neuronal differentiation. In conclusion, sodium arsenite exposure of human NSC induces the mitochondrial apoptotic pathway, which is substantially accelerated due to the simultaneous suppression of PI3K–AKT. Sodium arsenite also negatively affects neuronal differentiation of NSC through overactivation of MEK–ERK and suppression of PI3K–AKT. - Highlights: ? Arsenite induces the mitochondrial apoptotic pathway in human neural stem cells. ? Arsenite-induced apoptosis is strongly upregulated by suppression of PI3K–AKT. ? Arsenite-induced apoptosis is strongly down-regulated by inhibition of JNK–cJun. ? Arsenite negatively affects neuronal differentiation by inhibition of PI3K–AKT.

  4. Role of copper in the regulation of CU, ZN-superoxide dismutase in human K562 erythroleukemia cells and human fibroblasts

    E-Print Network [OSTI]

    Yu, Dan

    1994-01-01T23:59:59.000Z

    Activation of the enzyme CU2Zn2-SUperoxide dismutase (CuZnSOD) by its copper cofactor was studied in K562 erythroleukemia cells and skin fibroblasts. K562 cells were incubated in medium supplemented with 0-50 IIM CUC12 or ZnCI2 for 24 h and extracts...

  5. Network signatures of cellular immortalization in human lymphoblastoid cell lines

    SciTech Connect (OSTI)

    Shim, Sung-Mi; Jung, So-Young; Nam, Hye-Young; Kim, Hye-Ryun; Lee, Mee-Hee; Kim, Jun-Woo; Han, Bok-Ghee [National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Osong 363-951 (Korea, Republic of)] [National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Osong 363-951 (Korea, Republic of); Jeon, Jae-Pil, E-mail: jaepiljeon@hanmail.net [Division of Brain Diseases, Center for Biomedical Science, Korea National Institute of Health, Osong 363-951 (Korea, Republic of)] [Division of Brain Diseases, Center for Biomedical Science, Korea National Institute of Health, Osong 363-951 (Korea, Republic of)

    2013-11-15T23:59:59.000Z

    Highlights: •We identified network signatures of LCL immortalization from transcriptomic profiles. •More than 41% of DEGs are possibly regulated by miRNAs in LCLs. •MicroRNA target genes in LCLs are involved in apoptosis and immune-related functions. •This approach is useful to find functional miRNA targets in specific cell conditions. -- Abstract: Human lymphoblastoid cell line (LCL) has been used as an in vitro cell model in genetic and pharmacogenomic studies, as well as a good model for studying gene expression regulatory machinery using integrated genomic analyses. In this study, we aimed to identify biological networks of LCL immortalization from transcriptomic profiles of microRNAs and their target genes in LCLs. We first selected differentially expressed genes (DEGs) and microRNAs (DEmiRs) between early passage LCLs (eLCLs) and terminally differentiated late passage LCLs (tLCLs). The in silico and correlation analysis of these DEGs and DEmiRs revealed that 1098 DEG–DEmiR pairs were found to be positively (n = 591 pairs) or negatively (n = 507 pairs) correlated with each other. More than 41% of DEGs are possibly regulated by miRNAs in LCL immortalizations. The target DEGs of DEmiRs were enriched for cellular functions associated with apoptosis, immune response, cell death, JAK–STAT cascade and lymphocyte activation while non-miRNA target DEGs were over-represented for basic cell metabolisms. The target DEGs correlated negatively with miR-548a-3p and miR-219-5p were significantly associated with protein kinase cascade, and the lymphocyte proliferation and apoptosis, respectively. In addition, the miR-106a and miR-424 clusters located in the X chromosome were enriched in DEmiR–mRNA pairs for LCL immortalization. In this study, the integrated transcriptomic analysis of LCLs could identify functional networks of biologically active microRNAs and their target genes involved in LCL immortalization.

  6. Molecular Signatures of Human Induced Pluripotent Stem Cells Highlight Sex Differences and Cancer Genes

    E-Print Network [OSTI]

    Anguera, Montserrat C.

    Although human induced pluripotent stem cells (hiPSCs) have enormous potential in regenerative medicine, their epigenetic variability suggests that some lines may not be suitable for human therapy. There are currently few ...

  7. Regulation of Hsp27 and Hsp70 expression in human and mouse skin construct models by caveolae following exposure to the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide

    SciTech Connect (OSTI)

    Black, Adrienne T. [Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Hayden, Patrick J. [MatTek Corporation, Ashland, MA (United States); Casillas, Robert P. [Battelle Memorial Institute, Columbus, OH (United States); Heck, Diane E. [Environmental Health, New York Medical College, Valhalla, NY (United States); Gerecke, Donald R. [Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Sinko, Patrick J. [Pharmaceutics, Rutgers University, Piscataway, NJ (United States); Laskin, Debra L. [Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Laskin, Jeffrey D., E-mail: jlaskin@eohsi.rutgers.edu [Environmental and Occupational Medicine, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ (United States)

    2011-06-01T23:59:59.000Z

    Dermal exposure to the vesicant sulfur mustard causes marked inflammation and tissue damage. Basal keratinocytes appear to be a major target of sulfur mustard. In the present studies, mechanisms mediating skin toxicity were examined using a mouse skin construct model and a full-thickness human skin equivalent (EpiDerm-FT{sup TM}). In both systems, administration of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide (CEES, 100-1000 {mu}M) at the air surface induced mRNA and protein expression of heat shock proteins 27 and 70 (Hsp27 and Hsp70). CEES treatment also resulted in increased expression of caveolin-1, the major structural component of caveolae. Immunohistochemistry revealed that Hsp27, Hsp70 and caveolin-1 were localized in basal and suprabasal layers of the epidermis. Caveolin-1 was also detected in fibroblasts in the dermal component of the full thickness human skin equivalent. Western blot analysis of caveolar membrane fractions isolated by sucrose density centrifugation demonstrated that Hsp27 and Hsp70 were localized in caveolae. Treatment of mouse keratinocytes with filipin III or methyl-{beta}-cyclodextrin, which disrupt caveolar structure, markedly suppressed CEES-induced Hsp27 and Hsp70 mRNA and protein expression. CEES treatment is known to activate JNK and p38 MAP kinases; in mouse keratinocytes, inhibition of these enzymes suppressed CEES-induced expression of Hsp27 and Hsp70. These data suggest that MAP kinases regulate Hsp 27 and Hsp70; moreover, caveolae-mediated regulation of heat shock protein expression may be important in the pathophysiology of vesicant-induced skin toxicity.

  8. Friction Induced Skin Tags

    E-Print Network [OSTI]

    Allegue, Francisco; Fachal, Carmen; Pérez-Pérez, Lidia

    2008-01-01T23:59:59.000Z

    Duplantis KL, Jones BH. Friction blisters. Pathophysiology,Friction Induced Skin Tags Francisco Allegue MD 1 , Carmenetiopathogenic role for friction. Introduction Skin tags (

  9. Expression and rearrangement of the ROS1 gene in human glioblastoma cells

    SciTech Connect (OSTI)

    Birchmeier, C.; Sharma, S.; Wigler, M.

    1987-12-01T23:59:59.000Z

    The human ROS1 gene, which possibly encodes a growth factor receptor, was found to be expressed in human tumor cell lines. In a survey of 45 different human cell lines, the authors found ROS1 to be expressed in glioblastoma-derived cell lines at high levels and not to be expressed at all, or expressed at very low levels, in the remaining cell lines. The ROS1 gene was present in normal copy numbers in all cell lines that expressed the gene. However, in one particular glioblastoma line, they detected a potentially activating mutation at the ROS1 locus.

  10. Urocortin 3 Marks Mature Human Primary and Embryonic Stem Cell-Derived Pancreatic Alpha and Beta

    E-Print Network [OSTI]

    Sander, Maike

    Urocortin 3 Marks Mature Human Primary and Embryonic Stem Cell-Derived Pancreatic Alpha and Beta (Ucn 3) is abundantly and exclusively expressed in mouse pancreatic beta cells where it regulates of mouse beta cells. These observations identify Ucn 3 as a potential beta cell maturation marker

  11. Cell-surface glycoproteins of human sarcomas: differential expression in normal and malignant tissues and cultured cells

    SciTech Connect (OSTI)

    Rettig, W.F.; Garin-Chesa, P.; Beresford, H.R.; Oettgen, H.F.; Melamed, M.R.; Old, L.J.

    1988-05-01T23:59:59.000Z

    Normal differentiation and malignant transformation of human cells are characterized by specific changes in surface antigen phenotype. In the present study, the authors have defined six cell-surface antigens of human sarcomas and normal mesenchymal cells, by using mixed hemadsorption assays and immunochemical methods for the analysis of cultured cells and immunohistochemical staining for the analysis of normal tissues and > 200 tumor specimens. Differential patterns of F19, F24, G171, G253, S5, and Thy-1 antigen expression were found to characterize (i) subsets of cultured sarcoma cell lines, (ii) cultured fibroblasts derived from various organs, (iii) normal resting and activated mesenchymal tissues, and (iv) sarcoma and nonmesenchymal tumor tissues. These results provide a basic surface antigenic map for cultured mesenchymal cells and mesenchymal tissues and permit the classification of human sarcomas according to their antigenic phenotypes.

  12. INTERACTIONS OF HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS WITH TOBACCO TREATED STREPTOCOCCUS MUTANS

    E-Print Network [OSTI]

    Zhou, Yaoqi

    INTERACTIONS OF HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS WITH TOBACCO TREATED STREPTOCOCCUS MUTANS such as S. mutans treated with cigarette smoke condensate (CSC) and nicotine have on human umbilical vein and supernatants will then be used to treat HUVEC cells for 72 hours before the media is collected and analyzed

  13. INTERACTIONS OF HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS WITH TOBACCO TREATED STREPTOCOCCUS MUTANS

    E-Print Network [OSTI]

    Zhou, Yaoqi

    INTERACTIONS OF HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS WITH TOBACCO TREATED STREPTOCOCCUS MUTANS of S. mutans UA 159 has on binding to Human Umbilical Vein Endothelial Cells (HUVEC) when treated to treat HUVECs for 72 hours and cytotoxicity was determined by lactate dehydrogenase (LDH) assays

  14. Monitoring individual human cells during exposure to environmental organic toxins: Synchrotron FTIR spectromicroscopy

    E-Print Network [OSTI]

    for Environmental Biotechnology, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 b Dept. of MaterialMonitoring individual human cells during exposure to environmental organic toxins: Synchrotron FTIR) are ubiquitous environmental toxins that are known rodent carcinogens and suspected human carcinogens. Human

  15. Investigation of a suppression of asymmetric cell kinetics (SACK) approach for ex vivo expansion of human hematopoietic stem cells

    E-Print Network [OSTI]

    Taghizadeh, Rouzbeh R

    2006-01-01T23:59:59.000Z

    Ex vivo expansion of hematopoietic stem cells (HSCs) is a long-standing challenge faced by both researchers and clinicians. To date, no robust, efficient method for the pure, ex vivo expansion of human HSCs has been ...

  16. Transgenic knockout mice with exclusively human sickle hemoglobinand sickle cell disease

    SciTech Connect (OSTI)

    Paszty, C.; Brion, C.; Manci, E.; Witkowska, E.; Stevens, M.; Narla, M.; Rubin, E.

    1997-06-13T23:59:59.000Z

    To create mice expressing exclusively human sicklehemoglobin (HbS), transgenic mice expressing human alpha-, gamma-, andbeta[S]-globin were generated and bred with knockout mice that haddeletions of the murine alpha- and beta-globin genes. These sickle cellmice have the major features (irreversibly sickled red cells, anemia,multiorgan pathology) found in humans with sickle cell disease and, assuch, represent a useful in vivo system to accelerate the development ofimproved therapies for this common genetic disease.

  17. Generation of Cardiomyocytes from Human Endogenous and Pluripotent Stem-Cell Derived Endothelial Cells

    E-Print Network [OSTI]

    Truong, Raymond

    2013-01-01T23:59:59.000Z

    through a 70 micron cell strainer to dissociate cellthrough a 45 micron cell strainer-capped FACS tube (Fisherthrough a 70 micron cell strainer to dissociate cell

  18. Terahertz spectroscopy of intrinsic biomarkers for non-melanoma skin Cecil S. Joseph1*

    E-Print Network [OSTI]

    Massachusetts at Lowell, University of

    Terahertz spectroscopy of intrinsic biomarkers for non-melanoma skin cancer. Cecil S. Joseph1 of human cancers. The aim of this study was to identify intrinsic biomarkers for non-melanoma skin cancer wave terahertz imaging, skin cancer imaging 1. INTRODUCTION 1.1 Non-Melanoma Skin Cancer Non-melanoma

  19. Lumican induces human corneal epithelial cell migration and integrin expression via ERK 1/2 signaling

    SciTech Connect (OSTI)

    Seomun, Young [Laboratory of Ophthalmology and Visual Science, Korean Eye Tissue and Gene Bank related to Blindness, College of Medicine, Catholic University of Korea, 505 Banpo-dong, Seocho-ku, Seoul 137-040 (Korea, Republic of); Joo, Choun-Ki [Laboratory of Ophthalmology and Visual Science, Korean Eye Tissue and Gene Bank related to Blindness, College of Medicine, Catholic University of Korea, 505 Banpo-dong, Seocho-ku, Seoul 137-040 (Korea, Republic of)], E-mail: ckjoo@catholic.ac.kr

    2008-07-18T23:59:59.000Z

    Lumican is a major proteoglycans of the human cornea. Lumican knock-out mice have been shown to lose corneal transparency and to display delayed wound healing. The purpose of this study was to define the role of lumican in corneal epithelial cell migration. Over-expression of lumican in human corneal epithelial (HCE-T) cells increased both cell migration and proliferation, and increased levels of integrins {alpha}2 and {beta}1. ERK 1/2 was also activated in lumican over-expressed cells. When we treated HCE-T cells with the ERK-specific inhibitor U0126, cell migration and the expression of integrin {beta}1 were completely blocked. These data provide evidence that lumican stimulates cell migration in the corneal epithelium by activating ERK 1/2, and point to a novel signaling pathway implicated in corneal epithelial cell migration.

  20. Deoxyelephantopin from Elephantopus scaber L. induces cell-cycle arrest and apoptosis in the human nasopharyngeal cancer CNE cells

    SciTech Connect (OSTI)

    Su, Miaoxian [Biology Programme (Formally Biology Dept.), School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR (China)] [Biology Programme (Formally Biology Dept.), School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR (China); Chung, Hau Yin, E-mail: anthonychung@cuhk.edu.hk [Biology Programme (Formally Biology Dept.), School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR (China); Food and Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR (China); Li, Yaolan [Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou (China) [Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou (China); Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drug Research, Guangzhou (China)

    2011-07-29T23:59:59.000Z

    Highlights: {yields} Deoxyelephantopin (ESD) inhibited cell proliferation in the human nasopharyngeal cancer CNE cells. {yields} ESD induced cell cycle arrest in S and G2/M phases via modulation of cell cycle regulatory proteins. {yields} ESD triggered apoptosis by dysfunction of mitochondria and induction of both intrinsic and extrinsic apoptotic signaling pathways. {yields} ESD also triggered Akt, ERK, and JNK signaling pathways. -- Abstract: Deoxyelephantopin (ESD), a naturally occurring sesquiterpene lactone present in the Chinese medicinal herb, Elephantopus scaber L. exerted anticancer effects on various cultured cancer cells. However, the cellular mechanisms by which it controls the development of the cancer cells are unavailable, particularly the human nasopharyngeal cancer CNE cells. In this study, we found that ESD inhibited the CNE cell proliferation. Cell cycle arrest in S and G2/M phases was also found. Western blotting analysis showed that modulation of cell cycle regulatory proteins was responsible for the ESD-induced cell cycle arrest. Besides, ESD also triggered apoptosis in CNE cells. Dysfunction in mitochondria was found to be associated with the ESD-induced apoptosis as evidenced by the loss of mitochondrial membrane potential ({Delta}{Psi}m), the translocation of cytochrome c, and the regulation of Bcl-2 family proteins. Despite the Western blotting analysis showed that both intrinsic and extrinsic apoptotic pathways (cleavage of caspases-3, -7, -8, -9, and -10) were triggered in the ESD-induced apoptosis, additional analysis also showed that the induction of apoptosis could be achieved by the caspase-independent manner. Besides, Akt, ERK and JNK pathways were found to involve in ESD-induced cell death. Overall, our findings provided the first evidence that ESD induced cell cycle arrest, and apoptosis in CNE cells. ESD could be a potential chemotherapeutic agent in the treatment of nasopharyngeal cancer (NPC).

  1. Mortalin antibody-conjugated quantum dot transfer from human mesenchymal stromal cells to breast cancer cells requires cell–cell interaction

    SciTech Connect (OSTI)

    Pietilä, Mika [National Institute of Advanced industrial Sciences and Technology, Tsukuba, Ibaraki 305 8562 (Japan); Lehenkari, Petri [Institute of Biomedicine, Department of Anatomy and Cell Biology, University of Oulu, Aapistie 7, P.O. Box 5000, FIN-90014 (Finland); Institute of Clinical Medicine, Division of Surgery, University of Oulu and Clinical Research Centre, Department of Surgery and Intensive Care, Oulu University Hospital, Aapistie 5a, P.O. Box 5000, FIN-90014 (Finland); Kuvaja, Paula [Institute of Biomedicine, Department of Anatomy and Cell Biology, University of Oulu, Aapistie 7, P.O. Box 5000, FIN-90014 (Finland); Department of Pathology, Oulu University Hospital, P.O. Box 50, FIN-90029 OYS, Oulu (Finland); Kaakinen, Mika [Biocenter Oulu, University of Oulu, P.O. Box 5000, FI-90014 (Finland); Kaul, Sunil C.; Wadhwa, Renu [National Institute of Advanced industrial Sciences and Technology, Tsukuba, Ibaraki 305 8562 (Japan); Uemura, Toshimasa, E-mail: t.uemura@aist.go.jp [National Institute of Advanced industrial Sciences and Technology, Tsukuba, Ibaraki 305 8562 (Japan)

    2013-11-01T23:59:59.000Z

    The role of tumor stroma in regulation of breast cancer growth has been widely studied. However, the details on the type of heterocellular cross-talk between stromal and breast cancer cells (BCCs) are still poorly known. In the present study, in order to investigate the intercellular communication between human mesenchymal stromal cells (hMSCs) and breast cancer cells (BCCs, MDA-MB-231), we recruited cell-internalizing quantum dots (i-QD) generated by conjugation of cell-internalizing anti-mortalin antibody and quantum dots (QD). Co-culture of illuminated and color-coded hMSCs (QD655) and BCCs (QD585) revealed the intercellular transfer of QD655 signal from hMSCs to BCCs. The amount of QD double positive BCCs increased gradually within 48 h of co-culture. We found prominent intercellular transfer of QD655 in hanging drop co-culture system and it was non-existent when hMSCs and BBCs cells were co-cultured in trans-well system lacking imminent cell–cell contact. Fluorescent and electron microscope analyses also supported that the direct cell-to-cell interactions may be required for the intercellular transfer of QD655 from hMSCs to BCCs. To the best of our knowledge, the study provides a first demonstration of transcellular crosstalk between stromal cells and BCCs that involve direct contact and may also include a transfer of mortalin, an anti-apoptotic and growth-promoting factor enriched in cancer cells.

  2. Reprogramming human somatic cells to pluripotency using RNA

    E-Print Network [OSTI]

    Angel, Matthew (Matthew M.)

    2012-01-01T23:59:59.000Z

    Somatic cells can be reprogrammed to a pluripotent stem-cell state by ectopic expression of defined proteins. However, existing reprogramming methods take several weeks, suffer from low efficiencies, and most use DNA-based ...

  3. Direct and indirect effects of alpha-particle irradiations of human prostate tumor cells

    E-Print Network [OSTI]

    Wang, Rong, Ph. D. Massachusetts Institute of Technology

    2005-01-01T23:59:59.000Z

    The objective of this project is to establish a model system to study the direct effect, the bystander effect and the combinational effect of alpha-particle irradiations of human prostate tumor cells, toward the goal of ...

  4. Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Kazutoshi Takahashi1

    E-Print Network [OSTI]

    Takada, Shoji

    diabetes and spinal cord injury(Thomson et al., 1998). Use of human embryos, however, faces ethical transplanted into blastocysts, mouse iPS cells can give rise to adult chimeras, which are competent

  5. Genetic engineering of human ES and iPS cells using TALE nucleases

    E-Print Network [OSTI]

    Hockemeyer, Dirk

    Targeted genetic engineering of human pluripotent cells is a prerequisite for exploiting their full potential. Such genetic manipulations can be achieved using site-specific nucleases. Here we engineered transcription ...

  6. In Vivo Volume and Hemoglobin Dynamics of Human Red Blood Cells

    E-Print Network [OSTI]

    Malka, Roy

    Human red blood cells (RBCs) lose ~30% of their volume and ~20% of their hemoglobin (Hb) content during their ~100-day lifespan in the bloodstream. These observations are well-documented, but the mechanisms for these volume ...

  7. PRECLINICAL STUDY Adult human mesenchymal stem cells enhance breast

    E-Print Network [OSTI]

    McLachlan, John

    - mary tumor growth of the estrogen receptor-positive, hormone-dependent breast carcinoma cell line MCF-7 in the presence or absence of estrogen in SCID/beige mice. We also show hormone-independent growth of MCF-7 cells. This increase in PgR expression indicates a link between MCF-7 cells and MSCs through ER-mediated signaling

  8. Anaphylatoxin C5a fails to promote prostacyclin release from cultured human endothelial cells

    SciTech Connect (OSTI)

    Lunberg, C.; Marceau, F.; Huey, R.; Hugli, T.E.

    1986-03-01T23:59:59.000Z

    A predominantly relaxing effect of C5a on isolated blood vessels has been reported, which is associated with prostacyclin release from the vessel wall. Further, the well known hypothensive effect of C5a, also associated with increased prostacyclin output and preventable by indomethacin, indicates an involvement of endothelial cells in this reaction. In this study the authors characterized the response to C5a of cultured human endothelial cells from umbilical vein as measured by prostacyclin release. Prostacyclin was quantitated by radioimmunoassay as 6-keto-PGF/sub 1..cap alpha../. Subcultured cells respond to histamine and mellitin with increased prostacyclin production, but do not respond to leukotriene C4 (LTC/sub 4/). Primary cultures, on the other hand, respond to LTC/sub 4/ and the histamine response is 7-fold greater for these cells than for subcultured cells. However, neither primary nor subcultured cells release prostacyclin following application of either human C5a (100 nM) or C3a (1 ..mu..M). Also, these cells fail to show specific binding sites for /sup 125/I-C5a. In contrast, endothelial cells in the presence of human PMNs challenged with C5a release prostacyclin. These data suggest that C5a has no direct effect on the endothelial cell, but rather activates this cell indirectly via mediators from other cells known to respond to C5a.

  9. Regulation Of Nf=kb And Mnsod In Low Dose Radiation Induced Adaptive Protection Of Mouse And Human Skin Cells

    SciTech Connect (OSTI)

    Jian Li

    2012-11-07T23:59:59.000Z

    A sampling of publications resulting from this grant is provided. One is on the subject of NF-κB-Mediated HER2 Overexpression in Radiation-Adaptive Resistance. Another is on NF-κB-mediated adaptive resistance to ionizing radiation.

  10. Osmotic stress affects functional properties of human melanoma cell lines

    E-Print Network [OSTI]

    La Porta, Caterina A M; Pasini, Maria; Laurson, Lasse; Alava, Mikko J; Zapperi, Stefano; Amar, Martine Ben

    2015-01-01T23:59:59.000Z

    Understanding the role of microenvironment in cancer growth and metastasis is a key issue for cancer research. Here, we study the effect of osmotic pressure on the functional properties of primary and metastatic melanoma cell lines. In particular, we experimentally quantify individual cell motility and transmigration capability. We then perform a circular scratch assay to study how a cancer cell front invades an empty space. Our results show that primary melanoma cells are sensitive to a low osmotic pressure, while metastatic cells are less. To better understand the experimental results, we introduce and study a continuous model for the dynamics of a cell layer and a stochastic discrete model for cell proliferation and diffusion. The two models capture essential features of the experimental results and allow to make predictions for a wide range of experimentally measurable parameters.

  11. KILLING OF TARGET CELLS DUE TO RADON PROGENY IN THE HUMAN LUNG

    E-Print Network [OSTI]

    Yu, K.N.

    KILLING OF TARGET CELLS DUE TO RADON PROGENY IN THE HUMAN LUNG B. M. F. Lau1 , D. Nikezic1,2 and K to inhaled radon progeny in the human lung. The present work uses the microdosimetric approach and determines/alleviate this discrepancy, including those based on different lung morpho- metry models(4) , different ethnic groups(5

  12. Transcriptome analysis of the human T lymphocyte cell line Jurkat and human peripheral blood mononuclear cells exposed to deoxynivalenol (DON): New mechanistic insights

    SciTech Connect (OSTI)

    Katika, Madhumohan R. [RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Wageningen (Netherlands) [RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Wageningen (Netherlands); Department of Health Risk Analysis and Toxicology, Maastricht University (Netherlands); Netherlands Toxicogenomics Centre (Netherlands)] [Netherlands; Hendriksen, Peter J.M. [RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Wageningen (Netherlands) [RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Wageningen (Netherlands); Netherlands Toxicogenomics Centre (Netherlands)] [Netherlands; Shao, Jia [RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Wageningen (Netherlands) [RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Wageningen (Netherlands); Department of Health Risk Analysis and Toxicology, Maastricht University (Netherlands); Netherlands Toxicogenomics Centre (Netherlands)] [Netherlands; Loveren, Henk van [Department of Health Risk Analysis and Toxicology, Maastricht University (Netherlands) [Department of Health Risk Analysis and Toxicology, Maastricht University (Netherlands); National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Netherlands Toxicogenomics Centre (Netherlands)] [Netherlands; Peijnenburg, Ad, E-mail: ad.peijnenburg@wur.nl [RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Wageningen (Netherlands) [RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Wageningen (Netherlands); Netherlands Toxicogenomics Centre (Netherlands)] [Netherlands

    2012-10-01T23:59:59.000Z

    Deoxynivalenol (DON) or vomitoxin is a commonly encountered type-B trichothecene mycotoxin, produced by Fusarium species predominantly found in cereals and grains. DON is known to exert toxic effects on the gastrointestinal, reproductive and neuroendocrine systems, and particularly on the immune system. Depending on dose and exposure time, it can either stimulate or suppress immune function. The main objective of this study was to obtain a deeper insight into DON-induced effects on lymphoid cells. For this, we exposed the human T-lymphocyte cell line Jurkat and human peripheral blood mononuclear cells (PBMCs) to various concentrations of DON for various times and examined gene expression changes by DNA microarray analysis. Jurkat cells were exposed to 0.25 and 0.5 ?M DON for 3, 6 and 24 h. Biological interpretation of the microarray data indicated that DON affects various processes in these cells: It upregulates genes involved in ribosome structure and function, RNA/protein synthesis and processing, endoplasmic reticulum (ER) stress, calcium-mediated signaling, mitochondrial function, oxidative stress, the NFAT and NF-?B/TNF-? pathways, T cell activation and apoptosis. The effects of DON on the expression of genes involved in ER stress, NFAT activation and apoptosis were confirmed by qRT-PCR. Other biochemical experiments confirmed that DON activates calcium-dependent proteins such as calcineurin and M-calpain that are known to be involved in T cell activation and apoptosis. Induction of T cell activation was also confirmed by demonstrating that DON activates NFATC1 and induces its translocation from the cytoplasm to the nucleus. For the gene expression profiling of PBMCs, cells were exposed to 2 and 4 ?M DON for 6 and 24 h. Comparison of the Jurkat microarray data with those obtained with PBMCs showed that most of the processes affected by DON in the Jurkat cell line were also affected in the PBMCs. -- Highlights: ? The human T cell line Jurkat and human PBMCs were exposed to DON. ? Whole-genome microarray experiments were performed. ? Microarray data indicates that DON affects ribosome and RNA/protein synthesis. ? DON treatment induces ER stress, calcium mediated signaling, NFAT and NF-?B. ? Exposure to DON induces T cell activation, oxidative stress and apoptosis.

  13. Regulation of E2F-1 gene expression in human breast cancer cells 

    E-Print Network [OSTI]

    Ngwenya, Sharon Khethiwe

    2005-08-29T23:59:59.000Z

    17?-Estradiol induces E2F-1 gene expression in ZR-75 and MCF-7 human breast cancer cells. Analysis of the E2F-1 gene promoter in MCF-7 cells previously showed that hormone-induced transactivation required interactions between ...

  14. Reprogramming of murine and human somatic cells using a single polycistronic vector

    E-Print Network [OSTI]

    Saha, Krishanu

    for the generation of patient-specific stem cells with the potential to bypass both the practical and ethical to form teratomas, generate chimeras, and contribute to the germline (1­8). This technology can be readily differentiated B cells (9­11). Without the ethical or practical concerns associated with human embryonic stem

  15. Carrier-mediated transport of valproic acid in BeWo cells, a human trophoblast cell line

    E-Print Network [OSTI]

    Utoguchi, Naoki; Audus, Kenneth L.

    2000-01-01T23:59:59.000Z

    et al., 1998), asymmetric transferrin transport (Van der Ende et al., 1990; Cerneus et al., 1993), asymmetric fatty acid transport (Liu et al., 1997), choline uptake (Eaton and Sooranna, 1998a), glucose modulation of arginine transport (Eaton... Costar Corporation for support of the Cellular and Molecular Biopharmaceutics Handling Laboratory. Utoguchi, N. and Audus, K.L. (2000) Carrier-mediated transport of valproic acid in BeWo cells, a human trophoblast cell line. Int. J. Pharm. 195, 115...

  16. ERK-dependent and -independent pathways trigger human neural progenitor cell migration

    SciTech Connect (OSTI)

    Moors, Michaela [Institut fuer Umweltmedizinische Forschung gGmbH at the Heinrich Heine-University, Group of Toxicology, Auf'm Hennekamp 50, 40225 Duesseldorf (Germany)]. E-mail: moors@uni-duesseldorf.de; Cline, Jason E. [Institut fuer Umweltmedizinische Forschung gGmbH at the Heinrich Heine-University, Group of Toxicology, Auf'm Hennekamp 50, 40225 Duesseldorf (Germany)]. E-mail: jason.cline@uni-duesseldorf.de; Abel, Josef [Institut fuer Umweltmedizinische Forschung gGmbH at the Heinrich Heine-University, Group of Toxicology, Auf'm Hennekamp 50, 40225 Duesseldorf (Germany)]. E-mail: josef.abel@uni-duesseldorf.de; Fritsche, Ellen [Institut fuer Umweltmedizinische Forschung gGmbH at the Heinrich Heine-University, Group of Toxicology, Auf'm Hennekamp 50, 40225 Duesseldorf (Germany)]. E-mail: ellen.fritsche@uni-duesseldorf.de

    2007-05-15T23:59:59.000Z

    Besides differentiation and apoptosis, cell migration is a basic process in brain development in which neural cells migrate several centimeters within the developing brain before reaching their proper positions and forming the right connections. For identifying signaling events that control neural migration and are therefore potential targets of chemicals to disturb normal brain development, we developed a human neurosphere-based migration assay based on normal human neural progenitor (NHNP) cells, in which the distance is measured that cells wander over time. Applying this assay, we investigated the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the regulation of NHNP cell migration. Exposure to model substances like ethanol or phorbol 12-myristate 13-acetate (PMA) revealed a correlation between ERK1/2 activation and cell migration. The participation of phospho-(P-) ERK1/2 was confirmed by exposure of the cells to the MEK inhibitor PD98059, which directly prohibits ERK1/2 phosphorylation and inhibited cell migration. We identified protein kinase C (PKC) and epidermal growth factor receptor (EGFR) as upstream signaling kinases governing ERK1/2 activation, thereby controlling NHNP cell migration. Additionally, treatments with src kinase inhibitors led to a diminished cell migration without affecting ERK1/2 phosphorylation. Based on these results, we postulate that migration of NHNP cells is controlled via ERK1/2-dependent and -independent pathways.

  17. The Dose-Response of Vitamin D on Cell Proliferation, Differentiation and Apoptosis in Human Osteosarcoma Cells

    E-Print Network [OSTI]

    Thompson, Lindsey M.

    2009-01-28T23:59:59.000Z

    , 1?,25-dihydroxyvitamin D3 (1,25D), is being increasingly recognized for its anti-cancer properties. The dose-response of 1,25D and 25-hydroxyvitamin D3 (25D) was examined on human osteosarcoma cell lines, SaOS-2 (tumorigenic, p53 null, metastatic... cell lines, SaOS-2 and 143B, were treated with 1,25D, 25D or an ethanol control respectively at concentrations ranging from 1-1000nM. Cellular proliferation was measured after 1,25D or 25D exposure using a cell viability assay (MTS), Ki67...

  18. Response of sensitive human ataxia and resistant T-1 cell lines to accelerated heavy ions

    SciTech Connect (OSTI)

    Tobias, C.A.; Blakely, E.A.; Chang, P.Y.; Lommel, L.; Roots, R.

    1983-07-01T23:59:59.000Z

    The radiation dose responses of fibroblast from a patient with Ataxia telangiectasis (AT-2SF) and an established line of human T-1 cells were studied. Nearly monoenergetic accelerated neon and argon ions were used at the Berkeley Bevalac with various residual range values. The LET of the particles varied from 30 keV/..mu..m to over 1000 keV/..mu..m. All Ataxia survival curves were exponential functions of the dose. Their radiosensitivity reached peak values at 100 to 200 keV/..mu..m. Human T-1 cells have effective sublethal damage repair as has been evidenced by split dose experiments, and they are much more resistant to low LET than to high LET radiation. The repair-misrepair model has been used to interpret these results. We have obtained mathematical expressions that describe the cross sections and inactivation coefficients for both human cell lines as a function of the LET and the type of particle used. The results suggest either that high-LET particles induce a greater number of radiolesions per track or that heavy-ions at high LET induce lesions that kill cells more effectively and that are different from those produced at low LET. We assume that the lesions induced in T-1 and Ataxia cells are qualitatively similar and that each cell line attempts to repair these lesions. The result in most irradiated Ataxia cells, however, is either lethal misrepair or incomplete repair leading to cell death. 63 references, 10 figures, 1 table.

  19. Activation of ERK mitogen-activated protein kinase in human cells by the mycotoxin patulin

    SciTech Connect (OSTI)

    Wu, T.-S. [Department of Life Sciences, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Road, Taichung, Taiwan (China); Yu, F.-Y. [Department of Life Sciences, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Road, Taichung, Taiwan (China); Su, C.-C. [Tian-Sheng Memorial Hospital, Tong kong, Ping-Tong, Taiwan (China); Kan, J.-C. [Department of Life Sciences, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Road, Taichung, Taiwan (China); Chung, C.-P. [Department of Life Sciences, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Road, Taichung, Taiwan (China); Liu, B.-H. [Department of Life Sciences, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Road, Taichung, Taiwan (China)]. E-mail: bingliu@csmu.edu.tw

    2005-09-01T23:59:59.000Z

    Patulin (PAT), a mycotoxin produced by certain species of Penicillium and Aspergillus, is often detectable in moldy fruits and their derivative products. PAT led to a concentration-dependent and time-dependent increase in phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in human embryonic kidney (HEK293) cells, human peripheral blood mononuclear cells (PBMCs), and Madin-Darby canine kidney (MDCK) cells. Exposure of HEK293 cells to concentrations above 5 {mu}M PAT for 30 min induced ERK1/2 phosphorylation; activation of ERK1/2 was also observed after 24 h incubation with 0.05 {mu}M of PAT. Treatment of human PBMCs for 30 min with 30 {mu}M PAT dramatically increased the phosphorylated ERK1/2 levels. Both MEK1/2 inhibitors, U0126 and PD98059, suppressed ERK1/2 activation in either HEK293 or MDCK cells. In HEK293 cells, U0126-mediated inhibition of PAT-induced ERK1/2 phosphorylation resulted in a significant decrease in levels of DNA damage, expressed as tail moment values, in the single cell gel electrophoresis assay. Conversely, U0126 did not affect cell viability, lactate dehydrogenase release, and the DNA synthesis rate in PAT-treated cultures. Exposure of HEK293 cells for 90 min to 15 {mu}M PAT elevated the levels of early growth response gene-1 (egr-1) mRNA, but not of c-fos, fosB, and junB mRNAs. These results indicate that in human cells, PAT causes a rapid and persistent activation of ERK1/2 and this signaling pathway plays an important role in mediating PAT-induced DNA damage and egr-1 gene expression.

  20. Enhanced growth medium and method for culturing human mammary epithelial cells

    DOE Patents [OSTI]

    Stampfer, Martha R. (7290 Sayre Dr., Oakland, CA 94611); Smith, Helene S. (5693 Cabot Dr., Oakland, CA 94611); Hackett, Adeline J. (82 Evergreen Dr., Orinda, CA 94563)

    1983-01-01T23:59:59.000Z

    Methods are disclosed for isolating and culturing human mammary epithelial cells of both normal and malignant origin. Tissue samples are digested with a mixture including the enzymes collagenase and hyaluronidase to produce clumps of cells substantially free from stroma and other undesired cellular material. Growing the clumps of cells in mass culture in an enriched medium containing particular growth factors allows for active cell proliferation and subculture. Clonal culture having plating efficiencies of up to 40% or greater may be obtained using individual cells derived from the mass culture by plating the cells on appropriate substrates in the enriched media. The clonal growth of cells so obtained is suitable for a quantitative assessment of the cytotoxicity of particular treatment. An exemplary assay for assessing the cytotoxicity of the drug adriamycin is presented.

  1. Selective destruction of mouse islet beta cells by human T lymphocytes in a newly-established humanized type 1 diabetic model

    SciTech Connect (OSTI)

    Zhao, Yong, E-mail: yongzhao@uic.edu [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States)] [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States); Guo, Chengshan; Hwang, David; Lin, Brian; Dingeldein, Michael; Mihailescu, Dan; Sam, Susan; Sidhwani, Seema [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States)] [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States); Zhang, Yongkang [Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612 (United States)] [Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Jain, Sumit [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States)] [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States); Skidgel, Randal A. [Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612 (United States)] [Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Prabhakar, Bellur S. [Department of Immunology and Microbiology, University of Illinois at Chicago, Chicago, IL 60612 (United States)] [Department of Immunology and Microbiology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Mazzone, Theodore [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States)] [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States); Holterman, Mark J. [Department of Surgery, University of Illinois at Chicago, Chicago, IL 60612 (United States)] [Department of Surgery, University of Illinois at Chicago, Chicago, IL 60612 (United States)

    2010-09-03T23:59:59.000Z

    Research highlights: {yields} Establish a human immune-mediated type 1 diabetic model in NOD-scid IL2r{gamma}{sup null} mice. {yields} Using the irradiated diabetic NOD mouse spleen mononuclear cells as trigger. {yields} The islet {beta} cells were selectively destroyed by infiltrated human T cells. {yields} The model can facilitate translational research to find a cure for type 1 diabetes. -- Abstract: Type 1 diabetes (T1D) is caused by a T cell-mediated autoimmune response that leads to the loss of insulin-producing {beta} cells. The optimal preclinical testing of promising therapies would be aided by a humanized immune-mediated T1D model. We develop this model in NOD-scid IL2r{gamma}{sup null} mice. The selective destruction of pancreatic islet {beta} cells was mediated by human T lymphocytes after an initial trigger was supplied by the injection of irradiated spleen mononuclear cells (SMC) from diabetic nonobese diabetic (NOD) mice. This resulted in severe insulitis, a marked loss of total {beta}-cell mass, and other related phenotypes of T1D. The migration of human T cells to pancreatic islets was controlled by the {beta} cell-produced highly conserved chemokine stromal cell-derived factor 1 (SDF-1) and its receptor C-X-C chemokine receptor (CXCR) 4, as demonstrated by in vivo blocking experiments using antibody to CXCR4. The specificity of humanized T cell-mediated immune responses against islet {beta} cells was generated by the local inflammatory microenvironment in pancreatic islets including human CD4{sup +} T cell infiltration and clonal expansion, and the mouse islet {beta}-cell-derived CD1d-mediated human iNKT activation. The selective destruction of mouse islet {beta} cells by a human T cell-mediated immune response in this humanized T1D model can mimic those observed in T1D patients. This model can provide a valuable tool for translational research into T1D.

  2. HISTORY OF SKIN GRAFTS and Hauben and colleagues2

    E-Print Network [OSTI]

    Stanford University

    report of successful pinch grafts. Ollier in 1872 pointed out the importance of the dermis in skin grafts, Vandeput, and Olley4 gave us the technology to expand skin grafts with a machine that would cut the graft technology was published by Rheinwald and Green,5 and in 1979 cultured human keratinocytes were grown to form

  3. Gap Junctions and Connexon Hemichannels in Human Embryonic Stem Cells

    E-Print Network [OSTI]

    Huettner, James E.

    cells main- tained in vitro expressed RNA for 18 of the 20 known connexins; only connexin 40.1 (Cx40.1) and Cx50 were not detected by reverse transcription-polymerase chain reac- tion. Cx40, Cx43, and Cx45 communication that is observed in early embryos [3, 4]. More than 20 different connexin (Cx) subunits

  4. Stable overexpression of Smad7 in human melanoma cells inhibits their tumorigenicity in vitro and in vivo

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    Stable overexpression of Smad7 in human melanoma cells inhibits their tumorigenicity in vitro and 2 UMR 146 CNRS, Institut Curie, Orsay, France Running title: Autocrine TGF- and melanoma cell tumorigenicity Keywords: TGF-, Smad, Melanoma, Tumor Progression, Metalloproteinases, Angiogenesis Address

  5. aallll IIrreell aanndd ccaanncceerr ssttaattiissttiiccss sseeccoonndd rreeppoorrtt 11999988--22000000 Melanoma of the skin Melanoma of the skin

    E-Print Network [OSTI]

    Paxton, Anthony T.

    --22000000 46 Melanoma of the skin Melanoma of the skin Melanoma of the skin Melanoma of the skin Melanoma of the skin Melanoma of the skin Melanoma of the skin Melanoma of the skin Melanoma of the skin Melanoma of the skin Melanoma of the skin Melanoma of the skin Melanoma of the skin Melanoma of the skin Melanoma

  6. Triptolide, an Inhibitor of the Human Heat Shock Response That Enhances Stress-induced Cell Death*S

    E-Print Network [OSTI]

    Morimoto, Richard

    Triptolide, an Inhibitor of the Human Heat Shock Response That Enhances Stress-induced Cell Death chaperones, inducible by heat shock and a variety of other stresses, have critical roles in protein homeostasis, balancing cell stress with adaptation, survival, and cell death mechanisms. In transformed cells

  7. Skin metastases from lung cancer

    E-Print Network [OSTI]

    Mollet, Todd W; Garcia, Carlos A; Koester, Glenn

    2009-01-01T23:59:59.000Z

    cutaneous metastases from the lung frequently indicate aof skin metastases from lung cancer. Intern Med. 1996; 35:9. Coslett LM, Katlic MR. Lung cancer with skin metastasis.

  8. Peripheral blood derived mononuclear cells enhance osteoarthritic human chondrocyte migration

    E-Print Network [OSTI]

    Hopper, Niina; Henson, Frances; Brooks, Roger; Ali, Erden; Rushton, Neil; Wardale, John

    2015-01-01T23:59:59.000Z

    gradients [44, 45]. Experiments in young animals have shown that chondrocyte migration affects tissue-engineered cartilage integration by activating the signal transduction pathways involving Src, PLC?1, and ERK1/2 [46]. In order to begin to investigate... from the National Institute for Health Research. Abbreviations ACTB, actin beta; B2M, beta-2 microglobulin; BMP, bone morphogenic protein; CAPN, calpain; CI, cell index; ECM, extracellular matrix; ERK, extracellular signal regulated kinases; FBS...

  9. Generation of human cortical neurons from a new immortal fetal neural stem cell line

    SciTech Connect (OSTI)

    Cacci, E. [Laboratory of Neural Stem Cell Biology, Section of Restorative Neurology, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, BMC B10, Klinikgatan 26, University Hospital, SE-221 84 Lund (Sweden); Villa, A. [Laboratory of Human Neural Stem Cell Research, Center of Molecular Biology Severo Ochoa, Lab CX-450, Autonomous University of Madrid, 28049 Madrid (Spain); Parmar, M. [Division of Neurobiology, Wallenberg Neuroscience Center, Lund University, BMC A11, SE-221 84 Lund (Sweden); Cavallaro, M. [Laboratory of Neural Stem Cell Biology, Section of Restorative Neurology, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, BMC B10, Klinikgatan 26, University Hospital, SE-221 84 Lund (Sweden); Mandahl, N. [Department of Laboratory Medicine, Section of Clinical Genetics, University Hospital, SE-221 85 Lund (Sweden); Lindvall, O. [Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, University Hospital, SE-221 84 Lund (Sweden); Martinez-Serrano, A. [Laboratory of Human Neural Stem Cell Research, Center of Molecular Biology Severo Ochoa, Lab CX-450, Autonomous University of Madrid, 28049 Madrid (Spain); Kokaia, Z. [Laboratory of Neural Stem Cell Biology, Section of Restorative Neurology, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, BMC B10, Klinikgatan 26, University Hospital, SE-221 84 Lund (Sweden)]. E-mail: Zaal.Kokaia@med.lu.se

    2007-02-01T23:59:59.000Z

    Isolation and expansion of neural stem cells (NSCs) of human origin are crucial for successful development of cell therapy approaches in neurodegenerative diseases. Different epigenetic and genetic immortalization strategies have been established for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new, clonal NSC (hc-NSC) line, derived from human fetal cortical tissue, based on v-myc immortalization. Using immunocytochemistry, we show that these cells retain the characteristics of NSCs after more than 50 passages. Under proliferation conditions, when supplemented with epidermal and basic fibroblast growth factors, the hc-NSCs expressed neural stem/progenitor cell markers like nestin, vimentin and Sox2. When growth factors were withdrawn, proliferation and expression of v-myc and telomerase were dramatically reduced, and the hc-NSCs differentiated into glia and neurons (mostly glutamatergic and GABAergic, as well as tyrosine hydroxylase-positive, presumably dopaminergic neurons). RT-PCR analysis showed that the hc-NSCs retained expression of Pax6, Emx2 and Neurogenin2, which are genes associated with regionalization and cell commitment in cortical precursors during brain development. Our data indicate that this hc-NSC line could be useful for exploring the potential of human NSCs to replace dead or damaged cortical cells in animal models of acute and chronic neurodegenerative diseases. Taking advantage of its clonality and homogeneity, this cell line will also be a valuable experimental tool to study the regulatory role of intrinsic and extrinsic factors in human NSC biology.

  10. Elevated expression of ERK 2 in human tumor cells chronically treated with PD98059

    SciTech Connect (OSTI)

    Kanda, Shigeru [Department of Molecular Microbiology and Immunology, Division of Endothelial Cell Biology, Nagasaki University Graduate School of Biomedical Science, Nagasaki (Japan)]. E-mail: skanda-jua@umin.net; Kanetake, Hiroshi [Department of Urology, Nagasaki University Graduate School of Biomedical Science, Nagasaki (Japan); Miyata, Yasuyoshi [Department of Urology, Nagasaki University Graduate School of Biomedical Science, Nagasaki (Japan)

    2006-07-14T23:59:59.000Z

    We examined the effect of chronic exposure of tumor cells to a mitogen-activated protein kinase/extracellular signal-regulated kinases (ERK) kinase inhibitor, PD98059, on cell proliferation was investigated. Human renal carcinoma cells (ACHN) and prostatic carcinoma cells (DU145) were cultured in the presence of PD98059 for more than 4 weeks (denoted ACHN (PD) cells and DU145 (PD) cells, respectively) and proliferation and signal transduction pathways were examined. PD98059 significantly inhibited the proliferation of parental cells. However, PD98059 failed to inhibit proliferation of ACHN (PD) and DU145 (PD) cells significantly. Expression of ERK 1 and 2 was elevated in these cells. These phenotypes were reversible. Downregulation of ERK 2, but not ERK 1, by small interfering RNA significantly inhibited the proliferation of ACHN (PD) and DU145 (PD) cells. Taken together, chronic exposure of tumor cells to PD98059 induced elevated expression of ERK 2, which was associated with decreased sensitivity of cellular proliferation to PD98059.

  11. Intestinal-fatty acid binding protein and lipid transport in human intestinal epithelial cells

    SciTech Connect (OSTI)

    Montoudis, Alain [Department of Nutrition, Universite de Montreal and Research Center, CHU Sainte Justine, 3175 Cote Ste-Catherine, Montreal, Que., H3T 1C5 (Canada); Delvin, Edgard [Department of Biochemistry, Universite de Montreal and Research Center, CHU Sainte Justine, 3175 Cote Ste-Catherine, Montreal, Que., H3T 1C5 (Canada); Canadian Institute of Health Research, Group of the Functional Development and Physiopathology of the Digestive Tract, and Department of Anatomy and Cellular Biology, Faculty of Medicine and Health Sciences, Universite de Sherbrooke, Sherbrooke, Que., Canada J1H 5N4 (Canada); Menard, Daniel [Department of Pathology and Cell Biology, Universite de Montreal and Research Center, CHU Sainte Justine, 3175 Cote Ste-Catherine, Montreal, Que., H3T 1C5 (Canada); Canadian Institute of Health Research, Group of the Functional Development and Physiopathology of the Digestive Tract, and Department of Anatomy and Cellular Biology, Faculty of Medicine and Health Sciences, Universite de Sherbrooke, Sherbrooke, Que., J1H 5N4 (Canada)] (and others)

    2006-01-06T23:59:59.000Z

    Intestinal-fatty acid binding protein (I-FABP) is a 14-15 kDa cytoplasmic molecule highly expressed in the enterocyte. Although different functions have been proposed for various FABP family members, the specific function of I-FABP in human intestine remains unclear. Here, we studied the role of I-FABP in molecularly modified normal human intestinal epithelial cells (HIEC-6). cDNA transfection resulted in 90-fold I-FABP overexpression compared to cells treated with empty pQCXIP vector. The high-resolution immunogold technique revealed labeling mainly in the cytosol and confirmed the marked phenotype abundance of I-FABP in cDNA transfected cells. I-FABP overexpression was not associated with alterations in cell proliferation and viability. Studies using these transfected cells cultured with [{sup 14}C]oleic acid did not reveal higher efficiency in de novo synthesis or secretion of triglycerides, phospholipids, and cholesteryl esters compared to cells treated with empty pQCXIP vector only. Similarly, the incubation with [{sup 35}S]methionine did not disclose a superiority in the biogenesis of apolipoproteins (apo) A-I, A-IV, B-48, and B-100. Finally, cells transfected with I-FABP did not exhibit an increased production of chylomicrons, VLDL, LDL, and HDL. Our observations establish that I-FABP overexpression in normal HIEC-6 is not related to cell proliferation, lipid esterification, apo synthesis, and lipoprotein assembly, and, therefore, exclude its role in intestinal fat transport.

  12. In vitro model for human endothelial cell seeding of a small diameter vascular graft

    SciTech Connect (OSTI)

    Kent, K.C.; Oshima, A.; Ikemoto, T.; Whittemore, A.D.

    1988-07-01T23:59:59.000Z

    A precise system was devised to measure the kinetics of attachment of human venous endothelium to a variety of materials and substrates. Cells were labelled in a postconfluent state with tritiated thymidine, harvested, and a cell suspension seeded into a 4 mm PTFE graft. After a 90 minute incubation period, one half of the graft segment was sacrificed and the remaining portion placed in a perfusion system (225 cc/min) for 1 hour. Graft segments, effluents, and seeding suspension were assayed in a beta scintillation counter. The percentage of cells that attached pre- and postperfusion were determined, as well as the retrieval of tritium from the system. Initially, 71% of seeded cells attached to grafts coated with fibronectin, with significantly less (60%) remaining attached after perfusion. Only 10% of cells initially attached to uncoated grafts, with 4% retained postperfusion. Retrieval of tritium averaged 102 +/- 10% for all experiments. This system determines both pre- and postperfusion attachment of human endothelial cells to vascular grafts following manipulation of numerous variables, including graft material, substrate, incubation time, and seeding density. An optimal seeding protocol for human trials can thus be determined.

  13. Human T follicular helper and T follicular regulatory cell maintenance is independent of germinal centres

    E-Print Network [OSTI]

    Wallin, Elizabeth F.; Jolly, Elaine C.; Suchánek, Ond?ej; Bradley, J. Andrew; Espéli, Marion; Jayne, David R. W.; Linterman, Michelle A.; Smith, Kenneth G. C.

    2014-09-15T23:59:59.000Z

    with anti-CD20 monoclonal antibodies. Arthritis Research & Therapy. 2013;15(Suppl1):S3. 15 53. Slocombe T, Brown S, Miles K, Gray M, Barr TA, Gray D. Plasma cell homeostasis: the effects of chronic antigen stimulation and inflammation. J Immunol. Sep... ;111(32):11792-11797. 58. Marinova E, Han S, Zheng B. Human germinal center T cells are unique Th cells with high propensity for apoptosis induction. Int Immunol. Aug 2006;18(8):1337-1345. 59. Kim CH, Rott LS, Clark-Lewis I, Campbell DJ, Wu L, Butcher EC...

  14. Clonal Evolution of Pre-Leukemic Hematopoietic Stem Cells Precedes Human Acute Myeloid Leukemia

    E-Print Network [OSTI]

    Quake, Stephen R.

    Clonal Evolution of Pre-Leukemic Hematopoietic Stem Cells Precedes Human Acute Myeloid Leukemia Max-PAAuthorManuscriptNIH-PAAuthorManuscriptNIH-PAAuthorManuscript #12;INTRODUCTION Acute myeloid leukemia (AML) is an aggressive malignancy of hematopoietic progenitor (HSCs). We investigated this model through genomic analysis of HSCs from six patients with de novo acute

  15. Microliter-bioreactor array with buoyancy-driven stirring for human hematopoietic stem cell culture

    E-Print Network [OSTI]

    Meinhart, Carl

    Microliter-bioreactor array with buoyancy-driven stirring for human hematopoietic stem cell culture of bioreactors where finely con- trolled stirring is provided at the microliter scale 100­300 l . The microliter- bioreactor array is useful for performing protocol optimization in up to 96 parallel experiments

  16. Neuron, Vol. 43, 897905, September 16, 2004, Copyright 2004 by Cell Press Extinction Learning in Humans

    E-Print Network [OSTI]

    Phelps, Elizabeth

    that the mechanisms of extinction learning may be preserved across species. acquisition. However, when the rats wereNeuron, Vol. 43, 897­905, September 16, 2004, Copyright 2004 by Cell Press Extinction Learning in Humans: Role of the Amygdala and vmPFC CR). Extinction occurs when a CS is presented alone, without

  17. Monoclonal antibodies to human hemoglobin S and cell lines for the production thereof

    DOE Patents [OSTI]

    Jensen, R.H.; Vanderlaan, M.; Bigbee, W.L.; Stanker, L.H.; Branscomb, E.W.; Grabske, R.J.

    1984-11-29T23:59:59.000Z

    The present invention provides monoclonal antibodies specific to and distinguishing between hemoglobin S and hemoglobin A and methods for their production and use. These antibodies are capable of distinguishing between two hemoglobin types which differ from each other by only a single amino acid residue. The antibodies produced according to the present method are useful as immunofluorescent markers to enumerate circulating red blood cells which have the property of altered expression of the hemoglobin gene due to somatic mutation in stem cells. Such a measurement is contemplated as an assay for in vivo cellular somatic mutations in humans. Since the monoclonal antibodies produced in accordance with the instant invention exhibit a high degree of specificity to and greater affinity for hemoglobin S, they are suitable for labeling human red blood cells for flow cytometric detection of hemoglobin genotype. 4 figs.

  18. Monoclonal antibodies to human hemoglobin S and cell lines for the production thereof

    DOE Patents [OSTI]

    Jensen, Ronald H. (Livermore, CA); Vanderlaan, Martin (San Ramon, CA); Bigbee, William L. (Livermore, CA); Stanker, Larry H. (Livermore, CA); Branscomb, Elbert W. (Walnut Creek, CA); Grabske, Robert J. (Berkeley, CA)

    1988-01-01T23:59:59.000Z

    The present invention provides monoclonal antibodies specific to and distinguish between hemoglobin S and hemoglobin A and methods for their production and use. These antibodies are capable of distinguishing between two hemoglobin types which differ from each other by only a single amino acid residue. The antibodies produced according to the present method are useful as immunofluorescent markers to enumerate circulating red blood cells which have the property of altered expression of the hemoglobin gene due to somatic mutation in stem cells. Such a measurement is contemplated as an assay for in vivo cellular somatic mutations in humans. Since the monoclonal antibodies produced in accordance with the instant invention exhibit a high degree of specificity to and greater affinity for hemoglobin S, they are suitable for labeling human red blood cells for flow cytometric detection of hemoglobin genotype.

  19. Modeling human risk: Cell & molecular biology in context

    SciTech Connect (OSTI)

    NONE

    1997-06-01T23:59:59.000Z

    It is anticipated that early in the next century manned missions into outer space will occur, with a mission to Mars scheduled between 2015 and 2020. However, before such missions can be undertaken, a realistic estimation of the potential risks to the flight crews is required. One of the uncertainties remaining in this risk estimation is that posed by the effects of exposure to the radiation environment of outer space. Although the composition of this environment is fairly well understood, the biological effects arising from exposure to it are not. The reasons for this are three-fold: (1) A small but highly significant component of the radiation spectrum in outer space consists of highly charged, high energy (HZE) particles which are not routinely experienced on earth, and for which there are insufficient data on biological effects; (2) Most studies on the biological effects of radiation to date have been high-dose, high dose-rate, whereas in space, with the exception of solar particle events, radiation exposures will be low-dose, low dose-rate; (3) Although it has been established that the virtual absence of gravity in space has a profound effect on human physiology, it is not clear whether these effects will act synergistically with those of radiation exposure. A select panel will evaluate the utilizing experiments and models to accurately predict the risks associated with exposure to HZE particles. Topics of research include cellular and tissue response, health effects associated with radiation damage, model animal systems, and critical markers of Radiation response.

  20. Involvement of HIF-2?-mediated inflammation in arsenite-induced transformation of human bronchial epithelial cells

    SciTech Connect (OSTI)

    Xu, Yuan; Zhao, Yue; Xu, Wenchao; Luo, Fei; Wang, Bairu; Li, Yuan; Pang, Ying; Liu, Qizhan, E-mail: drqzliu@hotmail.com

    2013-10-15T23:59:59.000Z

    Arsenic is a well established human carcinogen that causes diseases of the lung. Some studies have suggested a link between inflammation and lung cancer; however, it is unknown if arsenite-induced inflammation causally contributes to arsenite-caused malignant transformation of cells. In this study, we investigated the molecular mechanisms underlying inflammation during neoplastic transformation induced in human bronchial epithelial (HBE) cells by chronic exposure to arsenite. The results showed that, on acute or chronic exposure to arsenite, HBE cells over-expressed the pro-inflammatory cytokines, interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1? (IL-1?). The data also indicated that HIF-2? was involved in arsenite-induced inflammation. Moreover, IL-6 and IL-8 were essential for the malignant progression of arsenite-transformed HBE cells. Thus, these experiments show that HIF-2? mediates arsenite-induced inflammation and that such inflammation is involved in arsenite-induced malignant transformation of HBE cells. The results provide a link between the inflammatory response and the acquisition of a malignant transformed phenotype by cells chronically exposed to arsenite and thus establish a previously unknown mechanism for arsenite-induced carcinogenesis. - Highlights: • Arsenite induces inflammation. • Arsenite-induced the increases of IL-6 and IL-8 via HIF-2?. • Inflammation is involved in arsenite-induced carcinogenesis.

  1. STAT3 signaling pathway is necessary for cell survival and tumorsphere forming capacity in ALDH{sup +}/CD133{sup +} stem cell-like human colon cancer cells

    SciTech Connect (OSTI)

    Lin, Li, E-mail: lin.796@osu.edu [Center for Childhood Cancer, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43205 (United States) [Center for Childhood Cancer, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43205 (United States); Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China); Fuchs, James; Li, Chenglong [Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210 (United States)] [Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210 (United States); Olson, Veronica [Center for Childhood Cancer, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43205 (United States)] [Center for Childhood Cancer, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43205 (United States); Bekaii-Saab, Tanios [Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43210 (United States)] [Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43210 (United States); Lin, Jiayuh, E-mail: lin.674@osu.edu [Center for Childhood Cancer, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43205 (United States)] [Center for Childhood Cancer, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43205 (United States)

    2011-12-16T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells. Black-Right-Pointing-Pointer STAT3 inhibitor, FLLL32 inhibits P-STAT3 and STAT3 target genes in colon cancer stem-like cells. Black-Right-Pointing-Pointer Inhibition of STAT3 resulted in decreased cell viability and reduced numbers of tumorspheres. Black-Right-Pointing-Pointer STAT3 is required for survival and tumorsphere forming capacity in colon cancer stem-like cells. Black-Right-Pointing-Pointer Targeting STAT3 in cancer stem-like cells may offer a novel treatment approach for colon cancer. -- Abstract: Persistent activation of Signal Transducers and Activators of Transcription 3 (STAT3) is frequently detected in colon cancer. Increasing evidence suggests the existence of a small population of colon cancer stem or cancer-initiating cells may be responsible for tumor initiation, metastasis, and resistance to chemotherapy and radiation. Whether STAT3 plays a role in colon cancer-initiating cells and the effect of STAT3 inhibition is still unknown. Flow cytometry was used to isolate colon cancer stem-like cells from three independent human colon cancer cell lines characterized by both aldehyde dehydrogenase (ALDH)-positive and CD133-positive subpopulation (ALDH{sup +}/CD133{sup +}). The effects of STAT3 inhibition in colon cancer stem-like cells were examined. The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells and was reduced by a STAT3-selective small molecular inhibitor, FLLL32. FLLL32 also inhibited the expression of potential STAT3 downstream target genes in colon cancer stem-like cells including survivin, Bcl-XL, as well as Notch-1, -3, and -4, which may be involved in stem cell function. Furthermore, FLLL32 inhibited cell viability and tumorsphere formation as well as induced cleaved caspase-3 in colon cancer stem-like cells. FLLL32 is more potent than curcumin as evidenced with lower IC50 in colon cancer stem-like cells. In summary, our results indicate that STAT3 is a novel therapeutic target in colon cancer stem-like cells and inhibition of STAT3 in cancer stem-like cells may offer a potential treatment for colorectal cancer.

  2. Uptake and cytotoxic effects of multi-walled carbon nanotubes in human bronchial epithelial cells

    SciTech Connect (OSTI)

    Hirano, Seishiro, E-mail: seishiro@nies.go.j [Environmental Nanotoxicology Section, RCER, National Institute for Environmental Studies (Japan); Fujitani, Yuji; Furuyama, Akiko [Environmental Nanotoxicology Section, RCER, National Institute for Environmental Studies (Japan); Kanno, Sanae [Photon Medical Research Center, Hamamatsu University School of Medicine (Japan)

    2010-11-15T23:59:59.000Z

    Carbon nanotubes (CNT) are cytotoxic to several cell types. However, the mechanism of CNT toxicity has not been fully studied, and dosimetric analyses of CNT in the cell culture system are lacking. Here, we describe a novel, high throughput method to measure cellular uptake of CNT using turbimetry. BEAS-2B, a human bronchial epithelial cell line, was used to investigate cellular uptake, cytotoxicity, and inflammatory effects of multi-walled CNT (MWCNT). The cytotoxicity of MWCNT was higher than that of crocidolite asbestos in BEAS-2B cells. The IC{sub 50} of MWCNT was 12 {mu}g/ml, whereas that of asbestos (crocidolite) was 678 {mu}g/ml. Over the course of 5 to 8 h, BEAS-2B cells took up 17-18% of the MWCNT when they were added to the culture medium at a concentration of 10 {mu}g/ml. BEAS-2B cells were exposed to 2, 5, or 10 {mu}g/ml of MWCNT, and total RNA was extracted for cytokine cDNA primer array assays. The culture supernatant was collected for cytokine antibody array assays. Cytokines IL-6 and IL-8 increased in a dose dependent manner at both the mRNA and protein levels. Migration inhibitory factor (MIF) also increased in the culture supernatant in response to MWCNT. A phosphokinase array study using lysates from BEAS-2B cells exposed to MWCNT indicated that phosphorylation of p38, ERK1, and HSP27 increased significantly in response to MWCNT. Results from a reporter gene assays using the NF-{kappa}B or AP-1 promoter linked to the luciferase gene in transiently transfected CHO-KI cells revealed that NF-{kappa}B was activated following MWCNT exposure, while AP-1 was not changed. Collectively, MWCNT activated NF-{kappa}B, enhanced phosphorylation of MAP kinase pathway components, and increased production of proinflammatory cytokines in human bronchial epithelial cells.

  3. Biphasic hormonal responses to the adrenocorticolytic DDT metabolite 3-methylsulfonyl-DDE in human cells

    SciTech Connect (OSTI)

    Asp, Vendela [Department of Environmental Toxicology, Uppsala University, Norbyvaegen 18 A, SE-752 36 Uppsala (Sweden); Ulleras, Erik [Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala (Sweden); Lindstroem, Veronica; Bergstroem, Ulrika [Department of Environmental Toxicology, Uppsala University, Norbyvaegen 18 A, SE-752 36 Uppsala (Sweden); Oskarsson, Agneta [Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala (Sweden); Brandt, Ingvar, E-mail: ingvar.brandt@ebc.uu.s [Department of Environmental Toxicology, Uppsala University, Norbyvaegen 18 A, SE-752 36 Uppsala (Sweden)

    2010-02-01T23:59:59.000Z

    The DDT metabolite 3-methylsulfonyl-DDE (3-MeSO{sub 2}-DDE) has been proposed as a lead compound for an improved adrenocortical carcinoma (ACC) treatment. ACC is a rare malignant disorder with poor prognosis, and the current pharmacological therapy o,p'-DDD (mitotane) has limited efficacy and causes severe adverse effects. 3-MeSO{sub 2}-DDE is bioactivated by cytochrome P450 (CYP) 11B1 in mice and causes formation of irreversibly bound protein adducts, reduced glucocorticoid secretion, and cell death in the adrenal cortex of several animal species. The present study was carried out to assess similarities and differences between mice and humans concerning the adrenocorticolytic effects of 3-MeSO{sub 2}-DDE. The results support previous indications that humans are sensitive to the adrenocorticolytic actions of 3-MeSO{sub 2}-DDE by demonstrating protein adduct formation and cytotoxicity in the human adrenocortical cell line H295R. However, neither the irreversible binding nor the cytotoxicity of 3-MeSO{sub 2}-DDE in H295R cells was inhibited by the CYP11B1 inhibitor etomidate. We also report biphasic responses to 3-MeSO{sub 2}-DDE in cortisol and aldosterone secretion as well as in mRNA levels of the steroidogenic genes StAR, CYP11B1 and CYP11B2. Hormone levels and mRNA levels were increased at lower concentrations of 3-MeSO{sub 2}-DDE, while higher concentrations decreased hormone levels. These biphasic responses were not observed with o,p'-DDD or with the precursor DDT metabolite p,p'-DDE. Based on these results, 3-MeSO{sub 2}-DDE remains a viable lead compound for drug design, although the adrenocorticolytic effects of 3-MeSO{sub 2}-DDE in human cells seem more complex than in murine cells.

  4. CDK-associated Cullin 1 promotes cell proliferation with activation of ERK1/2 in human lung cancer A549 cells

    SciTech Connect (OSTI)

    Chen, Tian Jun [Respiratory Department, The First Affiliated Hospital, Xi’an Jiaotong University College of Medicine, Xi’an 710061 (China)] [Respiratory Department, The First Affiliated Hospital, Xi’an Jiaotong University College of Medicine, Xi’an 710061 (China); Gao, Fei [Hua-shan Central Hospital of Xi’an, Xi’an 710043 (China)] [Hua-shan Central Hospital of Xi’an, Xi’an 710043 (China); Yang, Tian; Thakur, Asmitanand; Ren, Hui; Li, Yang; Zhang, Shuo; Wang, Ting [Respiratory Department, The First Affiliated Hospital, Xi’an Jiaotong University College of Medicine, Xi’an 710061 (China)] [Respiratory Department, The First Affiliated Hospital, Xi’an Jiaotong University College of Medicine, Xi’an 710061 (China); Chen, Ming Wei, E-mail: xjtucmw@163.com [Respiratory Department, The First Affiliated Hospital, Xi’an Jiaotong University College of Medicine, Xi’an 710061 (China)

    2013-07-19T23:59:59.000Z

    Highlights: •CDK-associated Cullin 1 (CAC1) expression increases in human lung carcinoma. •CAC1 promotes the proliferation of lung cancer A549 cells. •CAC1 promotes human lung cancer A549 cell proliferation with activation of ERK1/2. -- Abstract: Lung cancer is one of the most common causes of cancer-related death in the world, but the mechanisms remain unknown. In this study, we investigated the expression of CDK-associated Cullin 1 (CAC1) in lung cancer, the effect of CAC1 on the proliferation of human lung cancer A549 cells, and the activation of signaling pathways of mitogen-activated protein kinases (MAPKs). Results showed that CAC1 expression was higher levels in human lung carcinoma than normal lung tissue, and CAC1 siRNA reduced the proliferation of lung cancer A549 cells by decreasing cell activity and cell division in vitro. The proportion of cells treated with CAC1 siRNA increased in the G1 phase and decreased in the S and G2/M phase, indicative of G1 cell cycle arrest. Furthermore, the proportions of early/late apoptosis in lung cancer A549 cells were enhanced with CAC1 siRNA treatment. It was also found that activation of extracellular signal-regulated protein kinase (ERK) and p38 signaling pathways were involved in the proliferation of A549 cells. After CAC1 siRNA treatment, p-ERK1/2 levels decreased, and meanwhile p-p38 level increased, A549 cell proliferation increased when ERK1/2 signaling is activated by PMA. Our findings demonstrated that CAC1 promoted the proliferation of human lung cancer A549 cells with activation of ERK1/2 signaling pathways, suggesting a potential cure target for treatment of human lung cancer.

  5. Soft inertial microfluidics for high throughput separation of bacteria from human blood cells

    SciTech Connect (OSTI)

    Wu, Zhigang; Willing, Ben; Bjerketorp, Joakim; Jansson, Janet K.; Hjort, Klas

    2009-01-05T23:59:59.000Z

    We developed a new approach to separate bacteria from human blood cells based on soft inertial force induced migration with flow defined curved and focused sample flow inside a microfluidic device. This approach relies on a combination of an asymmetrical sheath flow and proper channel geometry to generate a soft inertial force on the sample fluid in the curved and focused sample flow segment to deflect larger particles away while the smaller ones are kept on or near the original flow streamline. The curved and focused sample flow and inertial effect were visualized and verified using a fluorescent dye primed in the device. First the particle behavior was studied in detail using 9.9 and 1.0 {micro}m particles with a polymer-based prototype. The prototype device is compact with an active size of 3 mm{sup 2}. The soft inertial effect and deflection distance were proportional to the fluid Reynolds number (Re) and particle Reynolds number (Re{sub p}), respectively. We successfully demonstrated separation of bacteria (Escherichia coli) from human red blood cells at high cell concentrations (above 10{sup 8}/mL), using a sample flow rate of up to 18 {micro}L/min. This resulted in at least a 300-fold enrichment of bacteria at a wide range of flow rates with a controlled flow spreading. The separated cells were proven to be viable. Proteins from fractions before and after cell separation were analyzed by gel electrophoresis and staining to verify the removal of red blood cell proteins from the bacterial cell fraction. This novel microfluidic process is robust, reproducible, simple to perform, and has a high throughput compared to other cell sorting systems. Microfluidic systems based on these principles could easily be manufactured for clinical laboratory and biomedical applications.

  6. The plasticity of human breast carcinoma cells is more than epithelial to mesenchymal conversion

    SciTech Connect (OSTI)

    Petersen, Ole William; Nielsen, Helga Lind; Gudjonsson, Thorarinn; Villadsen, Ren& #233; Ronnov-Jessen, Lone; Bissell, Mina J.

    2001-05-12T23:59:59.000Z

    The human breast comprises three lineages: the luminal epithelial lineage, the myoepithelial lineage, and the mesenchymal lineage. It has been widely accepted that human breast neoplasia pertains only to the luminal epithelial lineage. In recent years, however, evidence has accumulated that neoplastic breast epithelial cells may be substantially more plastic in their differentiation repertoire than previously anticipated. Thus, along with an increasing availability of markers for the myoepithelial lineage, at least a partial differentiation towards this lineage is being revealed frequently. It has also become clear that conversions towards the mesenchymal lineage actually occur, referred to as epithelial to mesenchymal transitions. Indeed, some of the so-called myofibroblasts surrounding the tumor may indeed have an epithelial origin rather than a mesenchymal origin. Because myoepithelial cells, epithelial to mesenchymal transition-derived cells, genuine stromal cells and myofibroblasts share common markers, we now need to define a more ambitious set of markers to distinguish these cell types in the microenvironment of the tumors. This is necessary because the different microenvironments may confer different clinical outcomes. The aim of this commentary is to describe some of the inherent complexities in defining cellular phenotypes in the microenvironment of breast cancer and to expand wherever possible on the implications for tumor suppression and progression.

  7. Nukbone® promotes proliferation and osteoblastic differentiation of mesenchymal stem cells from human amniotic membrane

    SciTech Connect (OSTI)

    Rodríguez-Fuentes, Nayeli; Rodríguez-Hernández, Ana G. [Depto. Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510 (Mexico)] [Depto. Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510 (Mexico); Enríquez-Jiménez, Juana [Depto. Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), México City 14000 (Mexico)] [Depto. Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), México City 14000 (Mexico); Alcántara-Quintana, Luz E. [Subd. de Investigación, Centro Nacional de la Transfusión Sanguínea, Secretaria de Salud, Mexico City 07370 (Mexico)] [Subd. de Investigación, Centro Nacional de la Transfusión Sanguínea, Secretaria de Salud, Mexico City 07370 (Mexico); Fuentes-Mera, Lizeth [Depto. Biología Molecular e Histocompatibilidad, Hospital General “Dr. Manuel Gea González”, México City 4800 (Mexico)] [Depto. Biología Molecular e Histocompatibilidad, Hospital General “Dr. Manuel Gea González”, México City 4800 (Mexico); Piña-Barba, María C. [Depto. Materiales Metálicos y Cerámicos, Instituto de Investigaciones en Materiales, Universidad Nacional Autónoma de México (UNAM), México City 04510 (Mexico)] [Depto. Materiales Metálicos y Cerámicos, Instituto de Investigaciones en Materiales, Universidad Nacional Autónoma de México (UNAM), México City 04510 (Mexico); Zepeda-Rodríguez, Armando [Depto. Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), México City 04510 (Mexico)] [Depto. Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), México City 04510 (Mexico); and others

    2013-05-10T23:59:59.000Z

    Highlights: •Nukbone showed to be a good scaffold for adhesion, proliferation and differentiation of stem cells. •Nukbone induced osteoblastic differentiation of human mesenchymal stem cells. •Results showed that Nukbone offer an excellent option for bone tissue regeneration due to properties. -- Abstract: Bovine bone matrix Nukbone® (NKB) is an osseous tissue-engineering biomaterial that retains its mineral and organic phases and its natural bone topography and has been used as a xenoimplant for bone regeneration in clinics. There are not studies regarding its influence of the NKB in the behavior of cells during the repairing processes. The aim of this research is to demonstrate that NKB has an osteoinductive effect in human mesenchymal stem cells from amniotic membrane (AM-hMSCs). Results indicated that NKB favors the AM-hMSCs adhesion and proliferation up to 7 days in culture as shown by the scanning electron microscopy and proliferation measures using an alamarBlue assay. Furthermore, as demonstrated by reverse transcriptase polymerase chain reaction, it was detected that two gene expression markers of osteoblastic differentiation: the core binding factor and osteocalcin were higher for AM-hMSCs co-cultured with NKB in comparison with cultivated cells in absence of the biomaterial. As the results indicate, NKB possess the capability for inducing successfully the osteoblastic differentiation of AM-hMSC, so that, NKB is an excellent xenoimplant option for repairing bone tissue defects.

  8. Sprayed skin turbine component

    DOE Patents [OSTI]

    Allen, David B

    2013-06-04T23:59:59.000Z

    Fabricating a turbine component (50) by casting a core structure (30), forming an array of pits (24) in an outer surface (32) of the core structure, depositing a transient liquid phase (TLP) material (40) on the outer surface of the core structure, the TLP containing a melting-point depressant, depositing a skin (42) on the outer surface of the core structure over the TLP material, and heating the assembly, thus forming both a diffusion bond and a mechanical interlock between the skin and the core structure. The heating diffuses the melting-point depressant away from the interface. Subsurface cooling channels (35) may be formed by forming grooves (34) in the outer surface of the core structure, filling the grooves with a fugitive filler (36), depositing and bonding the skin (42), then removing the fugitive material.

  9. The pyrimidine nucleotide carrier PNC1 and mitochondrial trafficking of thymidine phosphates in cultured human cells

    SciTech Connect (OSTI)

    Franzolin, Elisa; Miazzi, Cristina; Frangini, Miriam; Palumbo, Elisa; Rampazzo, Chiara [Department of Biology, University of Padova, Via Ugo Bassi 58B, I-35131 Padova (Italy)] [Department of Biology, University of Padova, Via Ugo Bassi 58B, I-35131 Padova (Italy); Bianchi, Vera, E-mail: vbianchi@bio.unipd.it [Department of Biology, University of Padova, Via Ugo Bassi 58B, I-35131 Padova (Italy)] [Department of Biology, University of Padova, Via Ugo Bassi 58B, I-35131 Padova (Italy)

    2012-10-15T23:59:59.000Z

    In cycling cells cytosolic de novo synthesis of deoxynucleotides is the main source of precursors for mitochondrial (mt) DNA synthesis. The transfer of deoxynucleotides across the inner mt membrane requires protein carriers. PNC1, a SLC25 family member, exchanges pyrimidine nucleoside triphosphates in liposomes and its downregulation decreases mtUTP concentration in cultured cells. By an isotope-flow protocol we confirmed transport of uridine nucleotides by PNC1 in intact cultured cells and investigated PNC1 involvement in the mt trafficking of thymidine phosphates. Key features of our approach were the manipulation of PNC1 expression by RNA interference or inducible overexpression, the employment of cells proficient or deficient for cytosolic thymidine kinase (TK1) to distinguish the direction of flow of thymidine nucleotides across the mt membrane during short pulses with [{sup 3}H]-thymidine, the determination of mtdTTP specific radioactivity to quantitate the rate of mtdTTP export to the cytoplasm. Downregulation of PNC1 in TK1{sup -} cells increased labeled dTTP in mitochondria due to a reduced rate of export. Overexpression of PNC1 in TK1{sup +} cells increased mtdTTP pool size and radioactivity, suggesting an involvement in the import of thymidine phosphates. Thus PNC1 is a component of the network regulating the mtdTTP pool in human cells. -- Highlights: Black-Right-Pointing-Pointer Thymidine phosphates exchange between mitochondria and cytosol in mammalian cells. Black-Right-Pointing-Pointer siRNA-downregulation of PNC1 delays mitochondrial dTTP export in TK1{sup -} cells. Black-Right-Pointing-Pointer PNC1 overexpression accumulates dTTP in mitochondria of TK1{sup +} cells. Black-Right-Pointing-Pointer PNC1 exchanges thymidine nucleotides across the mitochondrial inner membrane. Black-Right-Pointing-Pointer PNC1 participates in the regulation of the mtdTTP pool supporting mtDNA synthesis.

  10. MELANOMA OF THE SKIN 10. MELANOMA OF THE SKIN

    E-Print Network [OSTI]

    Paxton, Anthony T.

    MELANOMA OF THE SKIN 85 10. MELANOMA OF THE SKIN 10.1. SUMMARY Melanoma of the skin was the seventh most common cancer in Ireland, accounting for 4.1% of all malignant neoplasms, excluding non-melanoma at approximately 5% per annum overall. The risk of developing melanoma up to the age of 74 was 1 in 89 for women

  11. Noscapine induces mitochondria-mediated apoptosis in human colon cancer cells in vivo and in vitro

    SciTech Connect (OSTI)

    Yang, Zi-Rong; Liu, Meng; Peng, Xiu-Lan; Lei, Xiao-Fei; Zhang, Ji-Xiang [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province (China)] [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province (China); Dong, Wei-Guo, E-mail: dongwg1966@yahoo.com.cn [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province (China)] [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province (China)

    2012-05-11T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer Noscapine inhibited cell viability of colon cancer in a time- and dose- dependent manner. Black-Right-Pointing-Pointer G{sub 2}/M phase arrest and chromatin condensation and nuclear fragmentation were induced. Black-Right-Pointing-Pointer Noscapine promoted apoptosis via mitochondrial pathways. Black-Right-Pointing-Pointer Tumorigenicity was inhibited by noscapine. -- Abstract: Noscapine, a phthalide isoquinoline alkaloid derived from opium, has been widely used as a cough suppressant for decades. Noscapine has recently been shown to potentiate the anti-cancer effects of several therapies by inducing apoptosis in various malignant cells without any detectable toxicity in cells or tissues. However, the mechanism by which noscapine induces apoptosis in colon cancer cells remains unclear. The signaling pathways by which noscapine induces apoptosis were investigated in colon cancer cell lines treated with various noscapine concentrations for 72 h, and a dose-dependent inhibition of cell viability was observed. Noscapine effectively inhibited the proliferation of LoVo cells in vitro (IC{sub 50} = 75 {mu}M). This cytotoxicity was reflected by cell cycle arrest at G{sub 2}/M and subsequent apoptosis, as indicated by increased chromatin condensation and fragmentation, the upregulation of Bax and cytochrome c (Cyt-c), the downregulation of survivin and Bcl-2, and the activation of caspase-3 and caspase-9. Moreover, in a xenograft tumor model in mice, noscapine injection clearly inhibited tumor growth via the induction of apoptosis, which was demonstrated using a TUNEL assay. These results suggest that noscapine induces apoptosis in colon cancer cells via mitochondrial pathways. Noscapine may be a safe and effective chemotherapeutic agent for the treatment of human colon cancer.

  12. Three-Dimensional Model on Thermal Response of Skin Subject to Laser Heating

    E-Print Network [OSTI]

    Zhang, Jun

    in human skin [3]. The #12;rst medical lasers were continuous beam lasers such as CO 2 laser, argon laser and Jun Zhang z Laboratory for High Performance Scienti#12;c Computing and Computer Simulation, Department to investigate the transient thermal response of human skin subject to laser heating. The temperature

  13. Disrupting the wall accumulation of human sperm cells by artificial corrugation

    E-Print Network [OSTI]

    H. A. Guidobaldi; Y. Jeyaram; C. A. Condat; M. Oviedo; I. Berdakin; V. V. Moshchalkov; L. C. Giojalas; A. V. Silhanek; V. I. Marconi

    2015-04-29T23:59:59.000Z

    Many self-propelled microorganisms are attracted to surfaces. This makes their dynamics in restricted geometries very different from that observed in the bulk. Swimming along walls is beneficial for directing and sorting cells, but may be detrimental if homogeneous populations are desired, such as in counting microchambers. In this work, we characterize the motion of human sperm cells $60 \\mu m$ long, strongly confined to $25 \\mu m$ shallow chambers. We investigate the nature of the cell trajectories between the confining surfaces and their accumulation near the borders. Observed cell trajectories are composed of a succession of quasi-circular and quasi-linear segments. This suggests that the cells follow a path of intermittent trappings near the top and bottom surfaces separated by stretches of quasi-free motion in between the two surfaces, as confirmed by depth resolved confocal microscopy studies. We show that the introduction of artificial petal-shaped corrugation in the lateral boundaries removes the tendency of cells to accumulate near the borders, an effect which we hypothesize may be valuable for microfluidic applications in biomedicine.

  14. A Comparative Study on Human Embryonic Stem Cell Patent Law in the United States, the European Patent Organization, and China

    E-Print Network [OSTI]

    Zhu, Huan

    2011-05-31T23:59:59.000Z

    With the recent developments in biotechnology, associated patent law issues have been a growing concern since the 1980s. Among all the subcategories within the general field of biotechnology, human embryonic stem cell ...

  15. Core Transcriptional Regulatory Circuit Controlled by the TAL1 Complex in Human T Cell Acute Lymphoblastic Leukemia

    E-Print Network [OSTI]

    Sanda, Takaomi

    The oncogenic transcription factor TAL1/SCL is aberrantly expressed in over 40% of cases of human T cell acute lymphoblastic leukemia (T-ALL), emphasizing its importance in the molecular pathogenesis of T-ALL. Here we ...

  16. CometChip: A High-throughput 96-Well Platform for Measuring DNA Damage in Microarrayed Human Cells

    E-Print Network [OSTI]

    Ge, Jing

    DNA damaging agents can promote aging, disease and cancer and they are ubiquitous in the environment and produced within human cells as normal cellular metabolites. Ironically, at high doses DNA damaging agents are also ...

  17. Cell, Vol. 103, 11211131, December 22, 2000, Copyright 2000 by Cell Press Human Upf Proteins Target an mRNA for

    E-Print Network [OSTI]

    Bedwell, David M.

    Cell, Vol. 103, 1121­1131, December 22, 2000, Copyright ©2000 by Cell Press Human Upf Proteins pro- neous nuclear ribonucleoprotein (hnRNP), Hrp1p, wasteins involved in NMD, hUpf2, hUpf3a, and hUpf are com- provide a downstream "mark" for a premature termina-plexed with hUpf1, in intact cells hUpf3a

  18. HER/ErbB Receptor Interactions and Signaling Patterns in Human Mammary Epithelial Cells

    SciTech Connect (OSTI)

    Zhang, Yi; Opresko, Lee K.; Shankaran, Harish; Chrisler, William B.; Wiley, H. S.; Resat, Haluk

    2009-10-31T23:59:59.000Z

    Knowledge about signaling pathways is typically compiled based on data gathered using different cell lines. This approach implicitly assumes that cell line dependence is not important, which can be misleading because different cell lines do not always respond to a particular stimulus in the same way. The lack of coherent data collected from closely related cellular systems can be detrimental to the efforts to understand the regulation of biological processes. In this study, we report the development of a library of human mammary epithelial (HME) cell lines which express endogenous levels of the cell surface receptor EGFR/HER1, and different levels of HER2 and HER3. Using our clone library, we have quantified the interactions among the HER1-3 receptors and systematically investigated the existing hypotheses about their interaction patterns. Contrary to earlier suggestions, we find that lateral interactions with HER2 do not lead to strong transactivation between EGFR and HER3. Our study identified HER2 as the dominant dimerization partner for both EGFR and HER3, and revealed that EGFR and HER3 activations are only weakly linked in HME cells. We have also quantified the time-dependent activation patterns of the downstream effectors Erk and Akt. We found that HER3 signaling makes the strongest contribution to Akt activation and that, stimulation of either EGFR or HER3 pathways activate Erk at significant levels. Our study shows that cell libraries formed from closely related clones can be a powerful resource for pursuing the quantitative investigations that are necessary for developing a systems level understanding of cell signaling.

  19. VEGF induces proliferation of human hair follicle dermal papilla cells through VEGFR-2-mediated activation of ERK

    SciTech Connect (OSTI)

    Li, Wei; Man, Xiao-Yong [Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009 (China)] [Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009 (China); Li, Chun-Ming [Department of Dermatology, Second Affiliated Hospital, Nanchang University School of Medicine, Nanchang, Jiangxi 330000 (China)] [Department of Dermatology, Second Affiliated Hospital, Nanchang University School of Medicine, Nanchang, Jiangxi 330000 (China); Chen, Jia-Qi; Zhou, Jiong; Cai, Sui-Qing; Lu, Zhong-Fa [Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009 (China)] [Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009 (China); Zheng, Min, E-mail: minz@zju.edu.cn [Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009 (China)] [Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009 (China)

    2012-08-15T23:59:59.000Z

    Vascular endothelial growth factor (VEGF) is one of the strongest regulators of physiological and pathological angiogenesis. VEGF receptor 2 (VEGFR-2), the primary receptor for VEGF, is thought to mediate major functional effects of VEGF. Previously, we have localized both VEGF and VEGFR-2 in human hair follicles. In this study, we further defined the expression and roles of VEGFR-2 on human hair follicle dermal papilla (DP) cells. The expression of VEGFR-2 on DP cells was examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis separately, and localization of VEGFR-2 was defined by immunofluorescence. The effect of VEGF on DP cells was analyzed by MTT assays and specific inhibitors. Finally, the role of VEGF involved in the signaling pathways was investigated by Western blot. RT-PCR and Western blot analysis demonstrated the expression of VEGFR-2 on DP cells. Immunostaining for VEGFR-2 showed strong signal on cultured human DP cells in vitro. Exogenous VEGF{sub 165} stimulated proliferation of DP cells in a dose-dependent manner. Furthermore, this stimulation was blocked by a VEGFR-2 neutralizing antibody (MAB3571) and an ERK inhibitor (PD98059). VEGF{sub 165}-induced phosphorylation of ERK1/2 was abolished by MAB3571 and PD98059, while the phosphorylation of p38, JNK and AKT were not changed by VEGF{sub 165}. Taken together, VEGFR-2 is expressed on primary human hair follicle DP cells and VEGF induces proliferation of DP cells through VEGFR-2/ERK pathway, but not p38, JNK or AKT signaling. -- Highlights: Black-Right-Pointing-Pointer We examine the expression of VEGFR-2 on cultured human dermal papilla (DP) cells. Black-Right-Pointing-Pointer VEGF{sub 165} stimulated proliferation of human DP cells in a dose-dependent manner. Black-Right-Pointing-Pointer This stimulation was through VEGFR-2-mediated activation of ERK.

  20. Skin contamination dosimeter

    DOE Patents [OSTI]

    Hamby, David M. (Corvallis, OR); Farsoni, Abdollah T. (Corvallis, OR); Cazalas, Edward (Corvallis, OR)

    2011-06-21T23:59:59.000Z

    A technique and device provides absolute skin dosimetry in real time at multiple tissue depths simultaneously. The device uses a phoswich detector which has multiple scintillators embedded at different depths within a non-scintillating material. A digital pulse processor connected to the phoswich detector measures a differential distribution (dN/dH) of count rate N as function of pulse height H for signals from each of the multiple scintillators. A digital processor computes in real time from the differential count-rate distribution for each of multiple scintillators an estimate of an ionizing radiation dose delivered to each of multiple depths of skin tissue corresponding to the multiple scintillators embedded at multiple corresponding depths within the non-scintillating material.

  1. Chlorobenzene induces oxidative stress in human lung epithelial cells in vitro

    SciTech Connect (OSTI)

    Feltens, Ralph, E-mail: ralph.feltens@ufz.d [UFZ- Helmholtz Centre for Environmental Research, Department of Environmental Immunology, Permoserstrasse 15, D-04318 Leipzig (Germany); UFZ- Helmholtz Centre for Environmental Research, Department of Proteomics, Permoserstrasse 15, D-04318 Leipzig (Germany); Moegel, Iljana, E-mail: iljana.moegel@ufz.d [UFZ- Helmholtz Centre for Environmental Research, Department of Environmental Immunology, Permoserstrasse 15, D-04318 Leipzig (Germany); Roeder-Stolinski, Carmen, E-mail: carmen.roeder-stolinski@ufz.d [UFZ- Helmholtz Centre for Environmental Research, Department of Environmental Immunology, Permoserstrasse 15, D-04318 Leipzig (Germany); Simon, Jan-Christoph, E-mail: Jan-Christoph.Simon@medizin.uni-leipzig.d [Leipzig University Medical Center, Clinic of Dermatology, Venerology and Allergology, Philipp-Rosenthal-Str. 23-25, D-4103 Leipzig (Germany); Herberth, Gunda, E-mail: gunda.herberth@ufz.d [UFZ- Helmholtz Centre for Environmental Research, Department of Environmental Immunology, Permoserstrasse 15, D-04318 Leipzig (Germany); Lehmann, Irina, E-mail: irina.lehmann@ufz.d [UFZ- Helmholtz Centre for Environmental Research, Department of Environmental Immunology, Permoserstrasse 15, D-04318 Leipzig (Germany)

    2010-01-01T23:59:59.000Z

    Chlorobenzene is a volatile organic compound (VOC) that is widely used as a solvent, degreasing agent and chemical intermediate in many industrial settings. Occupational studies have shown that acute and chronic exposure to chlorobenzene can cause irritation of the mucosa of the upper respiratory tract and eyes. Using in vitro assays, we have shown in a previous study that human bronchial epithelial cells release inflammatory mediators such as the cytokine monocyte chemoattractant protein-1 (MCP-1) in response to chlorobenzene. This response is mediated through the NF-kappaB signaling pathway. Here, we investigated the effects of monochlorobenzene on human lung cells, with emphasis on potential alterations of the redox equilibrium to clarify whether the chlorobenzene-induced inflammatory response in lung epithelial cells is caused via an oxidative stress-dependent mechanism. We found that expression of cellular markers for oxidative stress, such as heme oxygenase 1 (HO-1), glutathione S-transferase pi1 (GSTP1), superoxide dismutase 1 (SOD1), prostaglandin-endoperoxide synthase 2 (PTGS2) and dual specificity phosphatase 1 (DUSP1), were elevated in the presence of monochlorobenzene. Likewise, intracellular reactive oxygen species (ROS) were increased in response to exposure. However, in the presence of the antioxidants N-(2-mercaptopropionyl)-glycine (MPG) or bucillamine, chlorobenzene-induced upregulation of marker proteins and release of the inflammatory mediator MCP-1 are suppressed. These results complement our previous findings and point to an oxidative stress-mediated inflammatory response following chlorobenzene exposure.

  2. Activation of ERK and JNK signaling pathways by mycotoxin citrinin in human cells

    SciTech Connect (OSTI)

    Chang, C.-H.; Yu, F.-Y.; Wang, L.-T.; Lin, Y.-S. [Department of Biomedical Sciences, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Rd., Taichung 402, Taiwan (China); Liu, B.-H. [Department of Biomedical Sciences, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Rd., Taichung 402, Taiwan (China)], E-mail: bingliu@csmu.edu.tw

    2009-06-15T23:59:59.000Z

    Mycotoxin citrinin (CTN) is commonly found in foods and feeds that are contaminated/inoculated with Penicillium, Aspergillus and Monascus species. The exposure of human embryonic kidney (HEK293) and HeLa cells to CTN resulted in a dose-dependent increase in the phosphorylation of two major mitogen-activated protein kinases (MAPKs), ERK1/2 and JNK. In HEK293 cultures, the administering of CTN increased both the mRNA and protein levels of egr-1, c-fos and c-jun genes; additionally, the ERK1/2 pathway contributed to the upregulation of Egr-1 and c-Fos protein expression. CTN treatment also induced the transcription activity of Egr-1 and AP-1 proteins, as evidenced by luciferase reporter assays. Bioinformatic analyses indicated two genes Gadd45{beta} and MMP3 have Egr-1 and AP-1 response elements in their promoters, respectively. Furthermore, co-exposure of HEK293 cells to CTN and MAPK pathway inhibitors demonstrated that CTN increased the levels of Gadd45{beta} mRNA through ERK1/2 signaling pathway and up-regulated the MMP3 transcripts majorly via JNK pathway. Finally, CTN-triggered caspase 3 activity was significantly reduced in the presence of MAPK inhibitors. Our results suggest that CTN positively regulates ERK1/2 and JNK pathways as well as their downstream effectors in human cells; activated MAPK pathways are also involved in CTN-induced apoptosis.

  3. The orphan nuclear receptor Nur77 regulates decidual prolactin expression in human endometrial stromal cells

    SciTech Connect (OSTI)

    Jiang, Yue; Hu, Yali; Zhao, Jing; Zhen, Xin [Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 (China)] [Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 (China); Yan, Guijun, E-mail: yanguijun33@gmail.com [Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 (China)] [Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 (China); Sun, Haixiang, E-mail: stevensunz@163.com [Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 (China)] [Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 (China)

    2011-01-14T23:59:59.000Z

    Research highlights: {yields} Decidually produced PRL plays a key role during pregnancy. {yields} Overexpression of Nur77 increased PRL mRNA expression and enhanced decidual PRL promoter activity. {yields} Knockdown of Nur77 decreased decidual PRL secretion induced by 8-Br-cAMP and MPA. {yields} Nur77 is a novel transcription factor that plays an active role in decidual prolactin expression. -- Abstract: Prolactin (PRL) is synthesized and released by several extrapituitary tissues, including decidualized stromal cells. Despite the important role of decidual PRL during pregnancy, little is understood about the factors involved in the proper regulation of decidual PRL expression. Here we present evidence that the transcription factor Nur77 plays an active role in decidual prolactin expression in human endometrial stromal cells (hESCs). Nur77 mRNA expression in hESCs was significantly increased after decidualization stimulated by 8-Br-cAMP and medroxyprogesterone acetate (MPA). Adenovirus-mediated overexpression of Nur77 in hESCs markedly increased PRL mRNA expression and enhanced decidual PRL promoter (dPRL/-332Luc) activity in a concentration-dependent manner. Furthermore, knockdown of Nur77 in hESCs significantly decreased decidual PRL promoter activation and substantially attenuated PRL mRNA expression and PRL secretion (P < 0.01) induced by 8-Br-cAMP and MPA. These results demonstrate that Nur77 is a novel transcription factor that contributes significantly to the regulation of prolactin gene expression in human endometrial stromal cells.

  4. Induction of human breast cell carcinogenesis by triclocarban and intervention by curcumin

    SciTech Connect (OSTI)

    Sood, Shilpa; Choudhary, Shambhunath; Wang, Hwa-Chain Robert, E-mail: hcrwang@utk.edu

    2013-09-06T23:59:59.000Z

    Highlights: •Triclocarban exposure induces breast epithelial cell carcinogenesis. •Triclocarban induces the Erk–Nox pathway, ROS elevation, and DNA damage. •Physiological doses of triclocarban induce cellular carcinogenesis. •Non-cytotoxic curcumin blocks triclocarban-induced carcinogenesis and pathways. -- Abstract: More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens and co-carcinogens. To identify co-carcinogens with abilities to induce cellular pre-malignancy, we studied the activity of triclocarban (TCC), an antimicrobial agent commonly used in household and personal care products. Here, we demonstrated, for the first time, that chronic exposure to TCC at physiologically-achievable nanomolar concentrations resulted in progressive carcinogenesis of human breast cells from non-cancerous to pre-malignant. Pre-malignant carcinogenesis was measured by increasingly-acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth and increased cell proliferation, without acquisition of cellular tumorigenicity. Long-term TCC exposure also induced constitutive activation of the Erk–Nox pathway and increases of reactive oxygen species (ROS) in cells. A single TCC exposure induced transient induction of the Erk–Nox pathway, ROS elevation, increased cell proliferation, and DNA damage in not only non-cancerous breast cells but also breast cancer cells. Using these constitutively- and transiently-induced changes as endpoints, we revealed that non-cytotoxic curcumin was effective in intervention of TCC-induced cellular pre-malignancy. Our results lead us to suggest that the co-carcinogenic potential of TCC should be seriously considered in epidemiological studies to reveal the significance of TCC in the development of sporadic breast cancer. Using TCC-induced transient and constitutive endpoints as targets will likely help identify non-cytotoxic preventive agents, such as curcumin, effective in suppressing TCC-induced cellular pre-malignancy.

  5. Disrupting the wall accumulation of human sperm cells by artificial corrugation

    E-Print Network [OSTI]

    H. A. Guidobaldi; Y. Jeyaram; C. A. Condat; M. Oviedo; I. Berdakin; V. V. Moshchalkov; L. C. Giojalas; A. V. Silhanek; V. I. Marconi

    2015-01-07T23:59:59.000Z

    Many self-propelled microorganisms are attracted to surfaces. This makes their dynamics in restricted geometries very different from that observed in the bulk. Swimming along walls is beneficial for directing and sorting cells, but may be detrimental if homogeneous populations are desired, such as in counting microchambers. In this work, we characterize the motion of human sperm cells $\\sim$60$\\mu$m long, strongly confined to $\\sim$20$\\mu$m shallow chambers. We investigate the nature of the cell trajectories between the confining surfaces and their accumulation near the borders. Observed cell trajectories are composed of a succession of quasi-circular and quasi-linear segments. This suggests that the cells follow a path of intermittent trappings near the top and bottom surfaces separated by stretches of quasi-free motion in between the two surfaces. We show that the introduction of artificial petal-shaped corrugation in the lateral boundaries limits the accumulation near the borders and contributes to increase the concentration in the chamber interior. The steady state limit is achieved over times of the order of minutes, which agrees well with a theoretical estimate based on the assumption that the cell mean-square displacement is largely due to the quasi-linear segments. Pure quasi-circular trajectories would require several hours to stabilize. Our predictions also indicate that stabilization proceeds 2.5 times faster in the corrugated chambers than in the non-corrugated ones, which is another practical reason to prefer the former for microfluidic applications in biomedicine.

  6. Wnt interaction and extracellular release of prominin-1/CD133 in human malignant melanoma cells

    SciTech Connect (OSTI)

    Rappa, Germana [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Mercapide, Javier; Anzanello, Fabio [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); Le, Thuc T. [Nevada Cancer Institute, Las Vegas, NV 89135 (United States); Johlfs, Mary G. [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); Center for Diabetes and Obesity Prevention, Treatment, Research and Education, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Fiscus, Ronald R. [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Center for Diabetes and Obesity Prevention, Treatment, Research and Education, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Wilsch-Bräuninger, Michaela [Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstr. 108, 01307 Dresden (Germany); Corbeil, Denis [Tissue Engineering Laboratories (BIOTEC) and DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Tatzberg 47–49, 01307 Dresden, Germany Technische Universitat Dresden, Dresden (Germany); Lorico, Aurelio, E-mail: alorico@roseman.edu [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104 (United States)

    2013-04-01T23:59:59.000Z

    Prominin-1 (CD133) is the first identified gene of a novel class of pentaspan membrane glycoproteins. It is expressed by various epithelial and non-epithelial cells, and notably by stem and cancer stem cells. In non-cancerous cells such as neuro-epithelial and hematopoietic stem cells, prominin-1 is selectively concentrated in plasma membrane protrusions, and released into the extracellular milieu in association with small vesicles. Previously, we demonstrated that prominin-1 contributes to melanoma cells pro-metastatic properties and suggested that it may constitute a molecular target to prevent prominin-1-expressing melanomas from colonizing and growing in lymph nodes and distant organs. Here, we report that three distinct pools of prominin-1 co-exist in cultures of human FEMX-I metastatic melanoma. Morphologically, in addition to the plasma membrane localization, prominin-1 is found within the intracellular compartments, (e.g., Golgi apparatus) and in association with extracellular membrane vesicles. The latter prominin-1–positive structures appeared in three sizes (small, ?40 nm; intermediates ?40–80 nm, and large, >80 nm). Functionally, the down-regulation of prominin-1 in FEMX-I cells resulted in a significant reduction of number of lipid droplets as observed by coherent anti-Stokes Raman scattering image analysis and Oil red O staining, and surprisingly in a decrease in the nuclear localization of beta-catenin, a surrogate marker of Wnt activation. Moreover, the T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter activity was 2 to 4 times higher in parental than in prominin-1-knockdown cells. Collectively, our results point to Wnt signaling and/or release of prominin-1–containing membrane vesicles as mediators of the pro-metastatic activity of prominin-1 in FEMX-I melanoma. - Highlights: ? First report of release of prominin-1–containing microvesicles from cancer cells. ? Pro-metastatic role of prominin-1–containing microvesicles in FEMX-I melanoma. ? Down-regulation of prominin-1 results in decreased nuclear localization of ?-catenin. ? Wnt signaling as mediator of the pro-metastatic activity of prominin-1.

  7. Multiple Lineages of Human Breast Cancer Stem/Progenitor Cells Identified by Profiling with Stem Cell Markers

    E-Print Network [OSTI]

    2009-01-01T23:59:59.000Z

    Contributions PROCR + /ESA + MDA-MB-231 cells asymmetricallyvivo. A. PROCR + /ESA + MDA-MB-231 cells with 93.8 percentbreast cancer cell lines. In MDA-MB-231 cells, PROCR and

  8. Use of human stem cell derived cardiomyocytes to examine sunitinib mediated cardiotoxicity and electrophysiological alterations

    SciTech Connect (OSTI)

    Cohen, J.D., E-mail: jennifer.cohen@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Babiarz, J.E., E-mail: joshua.babiarz@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Abrams, R.M., E-mail: rory.abrams@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Guo, L., E-mail: liang.guo@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Kameoka, S., E-mail: sei.kameoka@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Chiao, E., E-mail: eric.chiao@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Taunton, J., E-mail: taunton@cmp.ucsf.edu [Howard Hughes Medical Institute, Cellular and Molecular Pharmacology, University California San Francisco, San Francisco, CA 94158 (United States); Kolaja, K.L., E-mail: kyle.kolaja@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States)

    2011-11-15T23:59:59.000Z

    Sunitinib, an oral tyrosine kinase inhibitor approved to treat advanced renal cell carcinoma and gastrointestinal stroma tumor, is associated with clinical cardiac toxicity. Although the precise mechanism of sunitinib cardiotoxicity is not known, both the key metabolic energy regulator, AMP-activated protein kinase (AMPK), and ribosomal S 6 kinase (RSK) have been hypothesized as causative, albeit based on rodent models. To study the mechanism of sunitinib-mediated cardiotoxicity in a human model, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) having electrophysiological and contractile properties of native cardiac tissue were investigated. Sunitinib was cardiotoxic in a dose-dependent manner with an IC{sub 50} in the low micromolar range, observed by a loss of cellular ATP, an increase in oxidized glutathione, and induction of apoptosis in iPSC-CMs. Pretreatment of iPSC-CMs with AMPK activators AICAR or metformin, increased the phosphorylation of pAMPK-T172 and pACC-S79, but only marginally attenuated sunitinib mediated cell death. Furthermore, additional inhibitors of AMPK were not directly cytotoxic to iPSC-CMs up to 250 {mu}M concentrations. Inhibition of RSK with a highly specific, irreversible, small molecule inhibitor (RSK-FMK-MEA) did not induce cytotoxicity in iPSC-CMs below 250 {mu}M. Extensive electrophysiological analysis of sunitinib and RSK-FMK-MEA mediated conduction effects were performed. Taken together, these findings suggest that inhibition of AMPK and RSK are not a major component of sunitinib-induced cardiotoxicity. Although the exact mechanism of cardiotoxicity of sunitinib is not known, it is likely due to inhibition of multiple kinases simultaneously. These data highlight the utility of human iPSC-CMs in investigating the potential molecular mechanisms underlying drug-induced cardiotoxicity. -- Highlights: Black-Right-Pointing-Pointer Cytoxic effect of sunitinib on human stem cell derived cardiomyocytes Black-Right-Pointing-Pointer Sunitinib causes ATP depletion, LDH release, GSH oxidation, and apoptosis Black-Right-Pointing-Pointer In vitro effects of sunitinib include changes in beat rate and amplitude Black-Right-Pointing-Pointer Sunitinib inhibits hERG and Nav1.5. Black-Right-Pointing-Pointer AMPK and RSK do not mediate sunitinib cardiotoxicity.

  9. MiTF links Erk1/2 kinase and p21CIP1/WAF1 activation after UVC radiation in normal human melanocytes and melanoma cells

    E-Print Network [OSTI]

    Liu, Feng; Singh, Amarinder; Yang, Zhen; Garcia, Angela; Kong, Yu; Meyskens, Frank L

    2010-01-01T23:59:59.000Z

    human melanocytes and melanoma cells. Molecular Cancer 2010Transcriptional regulation in melanoma. Hematol Oncol Clinamplified in malignant melanoma. Nature 4. Joo A, et al:

  10. MiTF links Erk1/2 kinase and p21 CIP1/WAF1 activation after UVC radiation in normal human melanocytes and melanoma cells.

    E-Print Network [OSTI]

    Liu, Feng; Singh, Amarinder; Yang, Zhen; Garcia, Angela; Kong, Yu; Meyskens, Frank L Jr

    2010-01-01T23:59:59.000Z

    human melanocytes and melanoma cells. Molecular Cancer 2010Transcriptional regulation in melanoma. Hematol Oncol Clinamplified in malignant melanoma. Nature 4. Joo A, et al:

  11. Rapid generation of human B-cell lymphomas via combined expression of Myc and Bcl2 and their use as a preclinical model for biological therapies

    E-Print Network [OSTI]

    Schweighofer, C D

    Although numerous mouse models of B-cell malignancy have been developed via the enforced expression of defined oncogenic lesions, the feasibility of generating lineage-defined human B-cell malignancies using mice reconstituted ...

  12. IL-27 inhibits epithelial-mesenchymal transition and angiogenic factor production in a STAT1-dominant pathway in human non-small cell lung cancer

    E-Print Network [OSTI]

    2013-01-01T23:59:59.000Z

    IL-27 directly restrains lung tumorigenicity by suppressingof human non-small cell lung cancer in SCID mice. J Clinfactor in non-small cell lung cancer. J Clin Invest 1998,

  13. Human CD34+ CD133+ Hematopoietic Stem Cells Cultured with Growth Factors Including Angptl5 Efficiently Engraft Adult NOD-SCID Il2r??/? (NSG) Mice

    E-Print Network [OSTI]

    Drake, Adam

    Increasing demand for human hematopoietic stem cells (HSCs) in clinical and research applications necessitates expansion of HSCs in vitro. Before these cells can be used they must be carefully evaluated to assess their ...

  14. Requirement of T-lymphokine-activated killer cell-originated protein kinase for TRAIL resistance of human HeLa cervical cancer cells

    SciTech Connect (OSTI)

    Kwon, Hyeok-Ran [Department of Biochemistry, College of Medicine, Konyang University, 685 Gasuwon-dong, Seo-gu, Daejeon 302-718 (Korea, Republic of)] [Department of Biochemistry, College of Medicine, Konyang University, 685 Gasuwon-dong, Seo-gu, Daejeon 302-718 (Korea, Republic of); Lee, Ki Won [Department of Bioscience and Biotechnology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701 (Korea, Republic of)] [Department of Bioscience and Biotechnology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701 (Korea, Republic of); Dong, Zigang [Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912 (United States)] [Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912 (United States); Lee, Kyung Bok [Department of Biochemistry, College of Medicine, Konyang University, 685 Gasuwon-dong, Seo-gu, Daejeon 302-718 (Korea, Republic of)] [Department of Biochemistry, College of Medicine, Konyang University, 685 Gasuwon-dong, Seo-gu, Daejeon 302-718 (Korea, Republic of); Oh, Sang-Muk, E-mail: sangmuk_oh@konyang.ac.kr [Department of Biochemistry, College of Medicine, Konyang University, 685 Gasuwon-dong, Seo-gu, Daejeon 302-718 (Korea, Republic of)] [Department of Biochemistry, College of Medicine, Konyang University, 685 Gasuwon-dong, Seo-gu, Daejeon 302-718 (Korea, Republic of)

    2010-01-01T23:59:59.000Z

    T-lymphokine-activated killer cell-originated protein kinase (TOPK) appears to be highly expressed in various cancer cells and to play an important role in maintaining proliferation of cancer cells. However, the underlying mechanism by which TOPK regulates growth of cancer cells remains elusive. Here we report that upregulated endogenous TOPK augments resistance of cancer cells to apoptosis induced by tumor necrosis factor-related apoptosis inducing ligand (TRAIL). Stable knocking down of TOPK markedly increased TRAIL-mediated apoptosis of human HeLa cervical cancer cells, as compared with control cells. Caspase 8 or caspase 3 activities in response to TRAIL were greatly incremented in TOPK-depleted cells. Ablation of TOPK negatively regulated TRAIL-mediated NF-{kappa}B activity. Furthermore, expression of NF-{kappa}B-dependent genes, FLICE-inhibitory protein (FLIP), inhibitor of apoptosis protein 1 (c-IAP1), or X-linked inhibitor of apoptosis protein (XIAP) was reduced in TOPK-depleted cells. Collectively, these findings demonstrated that TOPK contributed to TRAIL resistance of cancer cells via NF-{kappa}B activity, suggesting that TOPK might be a potential molecular target for successful cancer therapy using TRAIL.

  15. Adsorption of Human Papillomavirus 16 to live human sperm

    E-Print Network [OSTI]

    Ribbeck, Katharina

    Human Papillomaviruses (HPVs) are a diverse group of viruses that infect the skin and mucosal tissues of humans. A high-risk subgroup of HPVs is associated with virtually all cases of cervical cancer [1]–[3]. High-risk ...

  16. The human papillomavirus type 58 E7 oncoprotein modulates cell cycle regulatory proteins and abrogates cell cycle checkpoints

    SciTech Connect (OSTI)

    Zhang Weifang [Department of Medicine, University of Massachusetts Medical School, Worcester, MA (United States); Department of Microbiology, School of Medicine, Shandong University, Jinan, Shandong (China); Li Jing [Department of Microbiology, School of Medicine, Shandong University, Jinan, Shandong (China); Kanginakudru, Sriramana [Department of Medicine, University of Massachusetts Medical School, Worcester, MA (United States); Zhao Weiming [Department of Microbiology, School of Medicine, Shandong University, Jinan, Shandong (China); Yu Xiuping, E-mail: yuxp@sdu.edu.c [Department of Microbiology, School of Medicine, Shandong University, Jinan, Shandong (China); Chen, Jason J., E-mail: Jason.chen@umassmed.ed [Department of Medicine, University of Massachusetts Medical School, Worcester, MA (United States)

    2010-02-05T23:59:59.000Z

    HPV type 58 (HPV-58) is the third most common HPV type in cervical cancer from Eastern Asia, yet little is known about how it promotes carcinogenesis. In this study, we demonstrate that HPV-58 E7 significantly promoted the proliferation and extended the lifespan of primary human keratinocytes (PHKs). HPV-58 E7 abrogated the G1 and the postmitotic checkpoints, although less efficiently than HPV-16 E7. Consistent with these observations, HPV-58 E7 down-regulated the cellular tumor suppressor pRb to a lesser extent than HPV-16 E7. Similar to HPV-16 E7 expressing PHKs, Cdk2 remained active in HPV-58 E7 expressing PHKs despite the presence of elevated levels of p53 and p21. Interestingly, HPV-58 E7 down-regulated p130 more efficiently than HPV-16 E7. Our study demonstrates a correlation between the ability of down-regulating pRb/p130 and abrogating cell cycle checkpoints by HPV-58 E7, which also correlates with the biological risks of cervical cancer progression associated with HPV-58 infection.

  17. Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment

    SciTech Connect (OSTI)

    Sustarsic, Elahu G. [Edison Biotechnology Institute, 1 Watertower Drive, Athens, OH (United States) [Edison Biotechnology Institute, 1 Watertower Drive, Athens, OH (United States); Department of Biological Sciences, Ohio University, Athens, OH (United States); Junnila, Riia K. [Edison Biotechnology Institute, 1 Watertower Drive, Athens, OH (United States)] [Edison Biotechnology Institute, 1 Watertower Drive, Athens, OH (United States); Kopchick, John J., E-mail: kopchick@ohio.edu [Edison Biotechnology Institute, 1 Watertower Drive, Athens, OH (United States); Department of Biological Sciences, Ohio University, Athens, OH (United States); Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH (United States)

    2013-11-08T23:59:59.000Z

    Highlights: •Most cancer types of the NCI60 have sub-sets of cell lines with high GHR expression. •GHR is highly expressed in melanoma cell lines. •GHR is elevated in advanced stage IV metastatic tumors vs. stage III. •GH treatment of metastatic melanoma cell lines alters growth and cell signaling. -- Abstract: Accumulating evidence implicates the growth hormone receptor (GHR) in carcinogenesis. While multiple studies show evidence for expression of growth hormone (GH) and GHR mRNA in human cancer tissue, there is a lack of quantification and only a few cancer types have been investigated. The National Cancer Institute’s NCI60 panel includes 60 cancer cell lines from nine types of human cancer: breast, CNS, colon, leukemia, melanoma, non-small cell lung, ovarian, prostate and renal. We utilized this panel to quantify expression of GHR, GH, prolactin receptor (PRLR) and prolactin (PRL) mRNA with real-time RT qPCR. Both GHR and PRLR show a broad range of expression within and among most cancer types. Strikingly, GHR expression is nearly 50-fold higher in melanoma than in the panel as a whole. Analysis of human metastatic melanoma biopsies confirmed GHR gene expression in melanoma tissue. In these human biopsies, the level of GHR mRNA is elevated in advanced stage IV tumor samples compared to stage III. Due to the novel finding of high GHR in melanoma, we examined the effect of GH treatment on three NCI60 melanoma lines (MDA-MB-435, UACC-62 and SK-MEL-5). GH increased proliferation in two out of three cell lines tested. Further analysis revealed GH-induced activation of STAT5 and mTOR in a cell line dependent manner. In conclusion, we have identified cell lines and cancer types that are ideal to study the role of GH and PRL in cancer, yet have been largely overlooked. Furthermore, we found that human metastatic melanoma tumors express GHR and cell lines possess active GHRs that can modulate multiple signaling pathways and alter cell proliferation. Based on this data, GH could be a new therapeutic target in melanoma.

  18. Characterization of the role of ephrinB2 in human embryonic stem cell fate

    E-Print Network [OSTI]

    Palomares, Karina

    2012-01-01T23:59:59.000Z

    passed through a 40 µm strainer. Half of the cell suspensionthrough a 40 µm cell strainer. MEFs were depleted withthrough a 100 µm cell strainer. Following centrifugation,

  19. Formation of tRNA granules in the nucleus of heat-induced human cells

    SciTech Connect (OSTI)

    Miyagawa, Ryu [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan) [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Department of Biological Science, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654 (Japan); Mizuno, Rie [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan)] [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Watanabe, Kazunori, E-mail: watanabe@ric.u-tokyo.ac.jp [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan)] [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Ijiri, Kenichi [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan) [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Department of Biological Science, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654 (Japan)

    2012-02-03T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer tRNAs are tranlocated into the nucleus in heat-induced HeLa cells. Black-Right-Pointing-Pointer tRNAs form the unique granules in the nucleus. Black-Right-Pointing-Pointer tRNA ganules overlap with nuclear stress granules. -- Abstract: The stress response, which can trigger various physiological phenomena, is important for living organisms. For instance, a number of stress-induced granules such as P-body and stress granule have been identified. These granules are formed in the cytoplasm under stress conditions and are associated with translational inhibition and mRNA decay. In the nucleus, there is a focus named nuclear stress body (nSB) that distinguishes these structures from cytoplasmic stress granules. Many splicing factors and long non-coding RNA species localize in nSBs as a result of stress. Indeed, tRNAs respond to several kinds of stress such as heat, oxidation or starvation. Although nuclear accumulation of tRNAs occurs in starved Saccharomyces cerevisiae, this phenomenon is not found in mammalian cells. We observed that initiator tRNA{sup Met} (Meti) is actively translocated into the nucleus of human cells under heat stress. During this study, we identified unique granules of Meti that overlapped with nSBs. Similarly, elongator tRNA{sup Met} was translocated into the nucleus and formed granules during heat stress. Formation of tRNA granules is closely related to the translocation ratio. Then, all tRNAs may form the specific granules.

  20. Mechanisms of hormonal regulation of CAD gene expression and inhibition by Aryl hydrocarbon receptor agonist in human breast cancer cells

    E-Print Network [OSTI]

    Khan, Shaheen Munawar Ali

    2007-04-25T23:59:59.000Z

    -mediated pathway. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and other aryl hydrocarbon receptor (AhR) ligands suppress several E2-induced responses in the rodent uterus and mammary tumors and in human breast cancer cells. TCDD inhibited hormone...

  1. Mechanisms of Attachment of Tobacco-Treated Streptococcus mutans to Human Endothelial Cells Alyssa R. Miller1

    E-Print Network [OSTI]

    Zhou, Yaoqi

    Mechanisms of Attachment of Tobacco-Treated Streptococcus mutans to Human Endothelial Cells Alyssa to atherosclerosis. S. mutans were treated with different concentrations of nicotine and cigarette smoke condensate reagents, enolase antibody and purified DnaK, were also used to treat the HUVEC to observe the effects

  2. Am J Physiol Lung Cell Mol Physiol . Author manuscript Defective angiogenesis in hypoplastic human fetal lungs correlates with

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    Am J Physiol Lung Cell Mol Physiol . Author manuscript Page /1 12 Defective angiogenesis in hypoplastic human fetal lungs correlates with nitric oxide synthase deficiency that occurs despite enhanced.bourbon@inserm.fr > Abstract Lung hypoplasia (LH) is a life-threatening congenital abnormality with various causes. It involves

  3. Neutron skins and neutron stars

    SciTech Connect (OSTI)

    Piekarewicz, J. [Department of Physics, Florida State University, Tallahassee, FL 32306-4350 (United States)

    2013-11-07T23:59:59.000Z

    The neutron-skin thickness of heavy nuclei provides a fundamental link to the equation of state of neutron-rich matter, and hence to the properties of neutron stars. The Lead Radius Experiment ('PREX') at Jefferson Laboratory has recently provided the first model-independence evidence on the existence of a neutron-rich skin in {sup 208}Pb. In this contribution we examine how the increased accuracy in the determination of neutron skins expected from the commissioning of intense polarized electron beams may impact the physics of neutron stars.

  4. Sensitive skins and somatic processing for affective and sociable robots based upon a somatic alphabet approach

    E-Print Network [OSTI]

    Stiehl, Walter Daniel, 1980-

    2005-01-01T23:59:59.000Z

    The sense of touch is one of the most important senses of the human body. This thesis describes the biologically inspired design of "sensitive skins" for two different robotic platforms: Leonardo, a high degree-of-freedom, ...

  5. S.N.A.K.E. : a dynamically reconfigurable Artificial Sensate Skin

    E-Print Network [OSTI]

    Barroeta Pérez, Gerardo

    2006-01-01T23:59:59.000Z

    The idea of an Artificial Sensate Skin device that mimics the characteristics and functions of its analogous living tissue whether human or animal is not new. Yet, most of the current related work has been focused in the ...

  6. Apoptosis induction by silica nanoparticles mediated through reactive oxygen species in human liver cell line HepG2

    SciTech Connect (OSTI)

    Ahmad, Javed [Department of Zoology, College of Science, King Saud University, Riyadh 11451 (Saudi Arabia)] [Department of Zoology, College of Science, King Saud University, Riyadh 11451 (Saudi Arabia); Ahamed, Maqusood, E-mail: maqusood@gmail.com [King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11451 (Saudi Arabia)] [King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11451 (Saudi Arabia); Akhtar, Mohd Javed [Fibre Toxicology, CSIR-Indian Institute of Toxicology Research, Lucknow-226001 (India)] [Fibre Toxicology, CSIR-Indian Institute of Toxicology Research, Lucknow-226001 (India); Alrokayan, Salman A. [King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11451 (Saudi Arabia)] [King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11451 (Saudi Arabia); Siddiqui, Maqsood A.; Musarrat, Javed; Al-Khedhairy, Abdulaziz A. [Department of Zoology, College of Science, King Saud University, Riyadh 11451 (Saudi Arabia)] [Department of Zoology, College of Science, King Saud University, Riyadh 11451 (Saudi Arabia)

    2012-03-01T23:59:59.000Z

    Silica nanoparticles are increasingly utilized in various applications including agriculture and medicine. In vivo studies have shown that liver is one of the primary target organ of silica nanoparticles. However, possible mechanisms of hepatotoxicity caused by silica nanoparticles still remain unclear. In this study, we explored the reactive oxygen species (ROS) mediated apoptosis induced by well-characterized 14 nm silica nanoparticles in human liver cell line HepG2. Silica nanoparticles (25–200 ?g/ml) induced a dose-dependent cytotoxicity in HepG2 cells. Silica nanoparticles were also found to induce oxidative stress in dose-dependent manner indicated by induction of ROS and lipid peroxidation and depletion of glutathione (GSH). Quantitative real-time PCR and immunoblotting results showed that both the mRNA and protein expressions of cell cycle checkpoint gene p53 and apoptotic genes (bax and caspase-3) were up-regulated while the anti-apoptotic gene bcl-2 was down-regulated in silica nanoparticles treated cells. Moreover, co-treatment of ROS scavenger vitamin C significantly attenuated the modulation of apoptotic markers along with the preservation of cell viability caused by silica nanoparticles. Our data demonstrated that silica nanoparticles induced apoptosis in human liver cells, which is ROS mediated and regulated through p53, bax/bcl-2 and caspase pathways. This study suggests that toxicity mechanisms of silica nanoparticles should be further investigated at in vivo level. -- Highlights: ? We explored the mechanisms of toxicity caused by silica NPs in human liver HepG2 cells. ? Silica NPs induced a dose-dependent cytotoxicity in HepG2 cells. ? Silica NPs induced ROS generation and oxidative stress in a dose-dependent manner. ? Silica NPs were also modulated apoptosis markers both at mRNA and protein levels. ? ROS mediated apoptosis induced by silica NPs was preserved by vitamin C.

  7. The ethanol extract of Scutellaria baicalensis and the active compounds induce cell cycle arrest and apoptosis including upregulation of p53 and Bax in human lung cancer cells

    SciTech Connect (OSTI)

    Gao Jiayu; Morgan, Winston A.; Sanchez-Medina, Alberto; Corcoran, Olivia, E-mail: o.corcoran@uel.ac.uk

    2011-08-01T23:59:59.000Z

    Despite a lack of scientific authentication, Scutellaria baicalensis is clinically used in Chinese medicine as a traditional adjuvant to chemotherapy of lung cancer. In this study, cytotoxicity assays demonstrated that crude ethanolic extracts of S. baicalensis were selectively toxic to human lung cancer cell lines A549, SK-LU-1 and SK-MES-1 compared with normal human lung fibroblasts. The active compounds baicalin, baicalein and wogonin did not exhibit such selectivity. Following exposure to the crude extracts, cellular protein expression in the cancer cell lines was assessed using 2D gel electrophoresis coupled with MALDI-TOF-MS/Protein Fingerprinting. The altered protein expression indicated that cell growth arrest and apoptosis were potential mechanisms of cytotoxicity. These observations were supported by PI staining cell cycle analysis using flow cytometry and Annexin-V apoptotic analysis by fluorescence microscopy of cancer cells treated with the crude extract and pure active compounds. Moreover, specific immunoblotting identification showed the decreased expression of cyclin A results in the S phase arrest of A549 whereas the G{sub 0}/G{sub 1} phase arrest in SK-MES-1 cells results from the decreased expression of cyclin D1. Following treatment, increased expression in the cancer cells of key proteins related to the enhancement of apoptosis was observed for p53 and Bax. These results provide further insight into the molecular mechanisms underlying the clinical use of this herb as an adjuvant to lung cancer therapy. - Research Highlights: > Scutellaria baicalensis is a clinical adjuvant to lung cancer chemotherapy in China. > Scutellaria ethanol extracts selectively toxic to A549, SK-LU-1 and SK-MES-1. > Baicalin, baicalein and wogonin were toxic to all lung cancer cell lines. > Proteomics identified increased p53 and BAX in response to Scutellaria extracts.

  8. Skinning Arbitrary Deformations Ladislav Kavan 1,2 Rachel McDonnell1 Simon Dobbyn1 Jiri Zara2 Carol O'Sullivan1

    E-Print Network [OSTI]

    Plotkin, Joshua B.

    , such as moving human or animal figures. In this paper, we demonstrate how to automatically construct skinning way of representing the animation of quasi- articulated objects, such as virtual characters, is known as skinning (or matrix palette skinning). It is based on the observation that an animation of a virtual

  9. MicroRNA-320a suppresses human colon cancer cell proliferation by directly targeting {beta}-catenin

    SciTech Connect (OSTI)

    Sun, Jian-Yong [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi'an (China) [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi'an (China); State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi'an (China); Huang, Yi [Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an (China)] [Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an (China); Li, Ji-Peng [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi'an (China)] [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi'an (China); Zhang, Xiang; Wang, Lei [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi'an (China)] [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi'an (China); Meng, Yan-Ling [Department of Immunology, Fourth Military Medical University, 710032 Xi'an (China)] [Department of Immunology, Fourth Military Medical University, 710032 Xi'an (China); Yan, Bo [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi'an (China)] [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi'an (China); Bian, Yong-Qian [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi'an (China)] [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi'an (China); Zhao, Jing [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi'an (China)] [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi'an (China); Wang, Wei-Zhong, E-mail: weichang@fmmu.edu.cn [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi'an (China)] [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi'an (China); and others

    2012-04-20T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer miR-320a is downregulated in human colorectal carcinoma. Black-Right-Pointing-Pointer Overexpression of miR-320a inhibits colon cancer cell proliferation. Black-Right-Pointing-Pointer {beta}-Catenin is a direct target of miR-320a in colon cancer cells. Black-Right-Pointing-Pointer miR-320a expression inversely correlates with mRNA expression of {beta}-catenin's target genes in human colon carcinoma. -- Abstract: Recent profile studies of microRNA (miRNA) expression have documented a deregulation of miRNA (miR-320a) in human colorectal carcinoma. However, its expression pattern and underlying mechanisms in the development and progression of colorectal carcinoma has not been elucidated clearly. Here, we performed real-time PCR to examine the expression levels of miR-320a in colon cancer cell lines and tumor tissues. And then, we investigated its biological functions in colon cancer cells by a gain of functional strategy. Further more, by the combinational approaches of bioinformatics and experimental validation, we confirmed target associations of miR-320a in colorectal carcinoma. Our results showed that miR-320a was frequently downregulated in cancer cell lines and colon cancer tissues. And we demonstrated that miR-320a restoration inhibited colon cancer cell proliferation and {beta}-catenin, a functionally oncogenic molecule was a direct target gene of miR-320a. Finally, the data of real-time PCR showed the reciprocal relationship between miR-320a and {beta}-catenin's downstream genes in colon cancer tissues. These findings indicate that miR-320a suppresses the growth of colon cancer cells by directly targeting {beta}-catenin, suggesting its application in prognosis prediction and cancer treatment.

  10. Lysophospholipid presentation by CD1d and recognition by a human Natural Killer T-cell receptor

    SciTech Connect (OSTI)

    López-Sagaseta, Jacinto; Sibener, Leah V.; Kung, Jennifer E.; Gumperz, Jenny; Adams, Erin J. (UC); (UW-MED)

    2014-10-02T23:59:59.000Z

    Invariant Natural Killer T (iNKT) cells use highly restricted {alpha}{beta} T cell receptors (TCRs) to probe the repertoire of lipids presented by CD1d molecules. Here, we describe our studies of lysophosphatidylcholine (LPC) presentation by human CD1d and its recognition by a native, LPC-specific iNKT TCR. Human CD1d presenting LPC adopts an altered conformation from that of CD1d presenting glycolipid antigens, with a shifted {alpha}1 helix resulting in an open A pocket. Binding of the iNKT TCR requires a 7-{angstrom} displacement of the LPC headgroup but stabilizes the CD1d-LPC complex in a closed conformation. The iNKT TCR CDR loop footprint on CD1d-LPC is anchored by the conserved positioning of the CDR3{alpha} loop, whereas the remaining CDR loops are shifted, due in part to amino-acid differences in the CDR3{beta} and J{beta} segment used by this iNKT TCR. These findings provide insight into how lysophospholipids are presented by human CD1d molecules and how this complex is recognized by some, but not all, human iNKT cells.

  11. Peptide array-based screening of human mesenchymal stem cell-adhesive peptides derived from fibronectin type III domain

    SciTech Connect (OSTI)

    Okochi, Mina; Nomura, Shigeyuki; Kaga, Chiaki [Department of Biotechnology, School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 (Japan); Honda, Hiroyuki [Department of Biotechnology, School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 (Japan); MEXT Innovative Research Center for Preventive Medical Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 (Japan)], E-mail: honda@nubio.nagoya-u.ac.jp

    2008-06-20T23:59:59.000Z

    Human mesenchymal stem cell-adhesive peptides were screened based on the amino acid sequence of fibronectin type III domain 8-11 (FN-III{sub 8-11}) using a peptide array synthesized by the Fmoc-chemistry. Using hexameric peptide library of FN-III{sub 8-11} scan, we identified the ALNGR (Ala-Leu-Asn-Gly-Arg) peptide that induced cell adhesion as well as RGDS (Arg-Gly-Asp-Ser) peptide. After incubation for 2 h, approximately 68% of inoculated cells adhere to the ALNGR peptide disk. Adhesion inhibition assay with integrin antibodies showed that the ALNGR peptide interacts with integrin {beta}1 but not with {alpha}v{beta}3, indicating that the receptors for ALNGR are different from RGDS. Additionally, the ALNGR peptide expressed cell specificities for adhesion: cell adhesion was promoted for fibroblasts but not for keratinocytes or endotherial cells. The ALNGR peptide induced cell adhesion and promoted cell proliferation without changing its property. It is therefore useful for the construction of functional biomaterials.

  12. Expansion of human pluripotent stem cells with synthetic oolymer PMVE-alt-MA

    E-Print Network [OSTI]

    Chu, Wai Keung

    2011-01-01T23:59:59.000Z

    and incubated on ice. A cell strainer of 40-µm pore size wascollected by 100um cell strainer at day 7. The distributionµm were collected by cell strainer to represent the current

  13. A novel synthetic analog of militarin, MA-1 induces mitochondrial dependent apoptosis by ROS generation in human lung cancer cells

    SciTech Connect (OSTI)

    Yoon, Deok Hyo; Lim, Mi-Hee [Department of Biochemistry, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Lee, Yu Ran [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Sung, Gi-Ho [Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Suwon 404-707 (Korea, Republic of); Lee, Tae-Ho [R and D Center, Dong-A Pharmaceutical Co, Ltd, Yongin 446-905 (Korea, Republic of); Jeon, Byeong Hwa [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Cho, Jae Youl [Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Song, Won O. [Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 (United States); Park, Haeil [College of Pharmacy, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Choi, Sunga, E-mail: sachoi@cnu.ac.kr [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Kim, Tae Woong, E-mail: tawkim@kangwon.ac.kr [Department of Biochemistry, Kangwon National University, Chuncheon 200-701 (Korea, Republic of)

    2013-12-15T23:59:59.000Z

    A synthetic Militarin analog-1[(2R,3R,4R,5R)-1,6-bis(4-(2,4,4-trimethylpentan-2-yl)phenoxy) hexane-2,3,4,5-tetraol] is a novel derivative of constituents from Cordyceps militaris, which has been used to treat a variety of chronic diseases including inflammation, diabetes, hyperglycemia and cancers. Here, we report for the first time the synthesis of Militarin analog-1 (MA-1) and the apoptotic mechanism of MA-1 against human lung cancer cell lines. Treatment with MA-1 significantly inhibited the viability of 3 human lung cancer cell lines. The inhibition of viability and growth in MA-1-treated A549 cells with an IC{sub 50} of 5 ?M were mediated through apoptosis induction, as demonstrated by an increase in DNA fragmentation, sub-G{sub 0}/G{sub 1}-DNA fraction, nuclear condensation, and phosphatidylserine exposure. The apoptotic cell death caused mitochondrial membrane permeabilization through regulation of expression of the Bcl-2 family proteins, leading to cytochrome c release in a time-dependent manner. Subsequently, the final stage of apoptosis, activation of caspase-9/-3 and cleavage of poly (ADP ribose) polymerase, was induced. Furthermore, A549 lung cancer cells were more responsive to MA-1 than a bronchial epithelial cell line (BEAS-2B), involving the rapid generation of reactive oxygen species (ROS), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activation. The pharmacological inhibition of ROS generation and JNK/p38 MAPK exhibited attenuated DNA fragmentation in MA-1-induced apoptosis. Oral administration of MA-1 also retarded growth of A549 orthotopic xenografts. In conclusion, the present study indicates that the new synthetic derivative MA-1 triggers mitochondrial apoptosis through ROS generation and regulation of MAPKs and may be a potent therapeutic agent against human lung cancer. - Highlights: • We report a novel synthesized derivative, militarin analog-1 (MA-1). • MA-1-induced cancer cell death was triggered by the ROS generation through MAPKs. • The MA-1-induced cell death was also modulated by the mitochondria-mediated pathway. • The apoptotic cancer cell death by MA-1 was also exhibited in orthotopic xenografts. • Our findings suggest MA-1 as a clinically useful agent for human lung cancer.

  14. Expression of a functional extracellular calcium-sensing receptor in human aortic endothelial cells

    SciTech Connect (OSTI)

    Ziegelstein, Roy C. [Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Center, Division of Cardiology, Baltimore, MD 21224-2780 (United States); Xiong Yali [Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Center, Division of Cardiology, Baltimore, MD 21224-2780 (United States); He Chaoxia [Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Center, Division of Cardiology, Baltimore, MD 21224-2780 (United States); Hu Qinghua [Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Center, Division of Cardiology, Baltimore, MD 21224-2780 (United States)]. E-mail: qinghuaa@jhmi.edu

    2006-03-31T23:59:59.000Z

    Extracellular Ca{sup 2+} concentration ([Ca{sup 2+}]{sub o}) regulates the functions of many cell types through a G protein-coupled [Ca{sup 2+}]{sub o}-sensing receptor (CaR). Whether the receptor is functionally expressed in vascular endothelial cells is largely unknown. In cultured human aortic endothelial cells (HAEC), RT-PCR yielded the expected 555-bp product corresponding to the CaR, and CaR protein was demonstrated by fluorescence immunostaining and Western blot. RT-PCR also demonstrated the expression in HAEC of alternatively spliced variants of the CaR lacking exon 5. Although stimulation of fura 2-loaded HAEC by several CaR agonists (high [Ca{sup 2+}]{sub o}, neomycin, and gadolinium) failed to increase intracellular Ca{sup 2+} concentration ([Ca{sup 2+}]{sub i}), the CaR agonist spermine stimulated an increase in [Ca{sup 2+}]{sub i} that was diminished in buffer without Ca{sup 2+} and was abolished after depletion of an intracellular Ca{sup 2+} pool with thapsigargin or after blocking IP{sub 3}- and ryanodine receptor-mediated Ca{sup 2+} release with xestospongin C and with high concentration ryanodine, respectively. Spermine stimulated an increase in DAF-FM fluorescence in HAEC, consistent with NO production. Both the increase in [Ca{sup 2+}]{sub i} and in NO production were reduced or absent in HAEC transfected with siRNA specifically targeted to the CaR. HAEC express a functional CaR that responds to the endogenous polyamine spermine with an increase in [Ca{sup 2+}]{sub i}, primarily due to release of IP{sub 3}- and ryanodine-sensitive intracellular Ca{sup 2+} stores, leading to the production of NO. Expression of alternatively spliced variants of the CaR may result in the absence of a functional response to other known CaR agonists in HAEC.

  15. Differential transcriptional regulation of IL-8 expression by human airway epithelial cells exposed to diesel exhaust particles

    SciTech Connect (OSTI)

    Tal, Tamara L. [Curriculum in Toxicology, University of North Carolina, Chapel Hill (United States); Simmons, Steven O. [Integrated Systems Toxicology, National Health and Environmental Effects Research Laboratory, U.S. EPA (United States); Silbajoris, Robert; Dailey, Lisa [Environmental and Public Health, National Health and Environmental Effects Research Laboratory, U.S. EPA (United States); Cho, Seung-Hyun [Air Pollution Prevention Control Division, National Risk Management Research Laboratory, U.S. EPA (United States); Research Participation Program, Oak Ridge Institute for Science and Education, Oak Ridge (United States); Ramabhadran, Ram [Curriculum in Toxicology, University of North Carolina, Chapel Hill (United States); Integrated Systems Toxicology, National Health and Environmental Effects Research Laboratory, U.S. EPA (United States); Linak, William [Air Pollution Prevention Control Division, National Risk Management Research Laboratory, U.S. EPA (United States); Reed, William; Bromberg, Philip A. [Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina, Chapel Hill (United States); Samet, James M., E-mail: samet.james@epa.go [Curriculum in Toxicology, University of North Carolina, Chapel Hill (United States); Environmental and Public Health, National Health and Environmental Effects Research Laboratory, U.S. EPA (United States)

    2010-02-15T23:59:59.000Z

    Exposure to diesel exhaust particles (DEP) induces inflammatory signaling characterized by MAP kinase-mediated activation of NFkB and AP-1 in vitro and in bronchial biopsies obtained from human subjects exposed to DEP. NFkB and AP-1 activation results in the upregulation of genes involved in promoting inflammation in airway epithelial cells, a principal target of inhaled DEP. IL-8 is a proinflammatory chemokine expressed by the airway epithelium in response to environmental pollutants. The mechanism by which DEP exposure induces IL-8 expression is not well understood. In the current study, we sought to determine whether DEP with varying organic content induces IL-8 expression in lung epithelial cells, as well as, to develop a method to rapidly evaluate the upstream mechanism(s) by which DEP induces IL-8 expression. Exposure to DEP with varying organic content differentially induced IL-8 expression and IL-8 promoter activity human airway epithelial cells. Mutational analysis of the IL-8 promoter was also performed using recombinant human cell lines expressing reporters linked to the mutated promoters. Treatment with a low organic-containing DEP stimulated IL-8 expression by a mechanism that is predominantly NFkB-dependent. In contrast, exposure to high organic-containing DEP induced IL-8 expression independently of NFkB through a mechanism that requires AP-1 activity. Our study reveals that exposure to DEP of varying organic content induces proinflammatory gene expression through multiple specific mechanisms in human airway epithelial cells. The approaches used in the present study demonstrate the utility of a promoter-reporter assay ensemble for identifying transcriptional pathways activated by pollutant exposure.

  16. A Computational Model Incorporating Neural Stem Cell Dynamics Reproduces Glioma Incidence across the Lifespan in the Human Population

    E-Print Network [OSTI]

    Bauer, Roman; Stoll, Elizabeth

    2015-01-01T23:59:59.000Z

    Glioma is the most common form of primary brain tumor. Demographically, the risk of occurrence increases until old age. Here we present a novel computational model to reproduce the probability of glioma incidence across the lifespan. Previous mathematical models explaining glioma incidence are framed in a rather abstract way, and do not directly relate to empirical findings. To decrease this gap between theory and experimental observations, we incorporate recent data on cellular and molecular factors underlying gliomagenesis. Since evidence implicates the adult neural stem cell as the likely cell-of-origin of glioma, we have incorporated empirically-determined estimates of neural stem cell number, cell division rate, mutation rate and oncogenic potential into our model. We demonstrate that our model yields results which match actual demographic data in the human population. In particular, this model accounts for the observed peak incidence of glioma at approximately 80 years of age, without the need to assert...

  17. A critical comparison of human face rendering techniques

    E-Print Network [OSTI]

    Arizpe, Arturo Andrew

    2006-01-01T23:59:59.000Z

    Human skin exhibits complex light reflectance properties that make it difficult to render realistically. In recent years, many techniques have been introduced to render skin, with varying degrees of complexity and realism. ...

  18. Label-free separation of human embryonic stem cells (hESCs) and their cardiac derivatives using Raman spectroscopy

    SciTech Connect (OSTI)

    Chan, J W; Lieu, D K; Huser, T R; Li, R A

    2008-09-08T23:59:59.000Z

    Self-renewable, pluripotent human embryonic stem cells (hESCs) can be differentiated into cardiomyocytes (CMs), providing an unlimited source of cells for transplantation therapies. However, unlike certain cell lineages such as hematopoietic cells, CMs lack specific surface markers for convenient identification, physical separation, and enrichment. Identification by immunostaining of cardiac-specific proteins such as troponin requires permeabilization, which renders the cells unviable and non-recoverable. Ectopic expression of a reporter protein under the transcriptional control of a heart-specific promoter for identifying hESC-derived CMs (hESC-CMs) is useful for research but complicates potential clinical applications. The practical detection and removal of undifferentiated hESCs in a graft, which may lead to tumors, is also critical. Here, we demonstrate a non-destructive, label-free optical method based on Raman scattering to interrogate the intrinsic biochemical signatures of individual hESCs and their cardiac derivatives, allowing cells to be identified and classified. By combining the Raman spectroscopic data with multivariate statistical analysis, our results indicate that hESCs, human fetal left ventricular CMs, and hESC-CMs can be identified by their intrinsic biochemical characteristics with an accuracy of 96%, 98% and 66%, respectively. The present study lays the groundwork for developing a systematic and automated method for the non-invasive and label-free sorting of (i) high-quality hESCs for expansion, and (ii) ex vivo CMs (derived from embryonic or adult stem cells) for cell-based heart therapies.

  19. Hair follicles are required for optimal growth during lateral skin expansion 

    E-Print Network [OSTI]

    Heath, Jack; Langton, Abigail K.; Hammond, Nigel L.; Dixon, Michael J.; Overbeek, Paul A.

    2009-01-01T23:59:59.000Z

    The hair follicles and the interfollicular epidermis of intact mature skin are maintained by distinct stem cell populations. Upon wounding, however, emigration of hair follicle keratinocytes to the interfollicular epidermis plays a role in acute...

  20. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    SciTech Connect (OSTI)

    Stueckle, Todd A., E-mail: tstueckle@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Lu, Yongju, E-mail: yongju6@hotmail.com [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States)] [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Davis, Mary E., E-mail: mdavis@wvu.edu [Department of Physiology, West Virginia University, Morgantown, WV 26506 (United States); Wang, Liying, E-mail: lmw6@cdc.gov [Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States)] [Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Jiang, Bing-Hua, E-mail: bhjiang@jefferson.edu [Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 (United States)] [Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Holaskova, Ida, E-mail: iholaskova@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States)] [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Schafer, Rosana, E-mail: rschafer@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States)] [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Barnett, John B., E-mail: jbarnett@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Rojanasakul, Yon, E-mail: yrojan@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States)] [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States)

    2012-06-01T23:59:59.000Z

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-?B, MAPK and NCOR1 signaling disrupted PPAR?/?-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1?, Akt, MAPK, and NF-?B signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ? Chronic As{sub 2}O{sub 3} exposure to lung epithelial cells resulted in a cancer-like phenotype. ? Mice injected with arsenic transformed (B-As) cells displayed metastatic tumors. ? Microarray profiling revealed changes in mitochondrial metabolism and ROS response. ? p21, EF1?, Akt, MAPK, PPAR? and NF-?B networks promoted pro-cancer signaling. ? B-As cells represent a lung cancer model to explore As-associated carcinogenesis.

  1. MRP4 knockdown enhances migration, suppresses apoptosis, and produces aggregated morphology in human retinal vascular endothelial cells

    SciTech Connect (OSTI)

    Tagami, Mizuki [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan)] [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Kusuhara, Sentaro, E-mail: kusu@med.kobe-u.ac.jp [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan)] [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Imai, Hisanori [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan)] [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Uemura, Akiyoshi [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan) [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Department of Vascular Biology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Honda, Shigeru; Tsukahara, Yasutomo; Negi, Akira [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan)] [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan)

    2010-10-01T23:59:59.000Z

    Research highlights: {yields} Exogenous VEGF decreases MRP4 expression in a dose-dependent manner. {yields} MRP4 knockdown leads to enhanced cell migration. {yields} MRP4 knockdown suppresses caspase-3-mediated cell apoptosis. {yields} MRP4 knockdown produces cell assembly and cell aggregation. -- Abstract: The multidrug resistance protein (MRP) MRP4/ABCC4 is an ATP-binding cassette transporter that actively effluxes endogenous and xenobiotic substrates out of cells. In the rodent retina, Mrp4 mRNA and protein are exclusively expressed in vascular endothelial cells, but the angiogenic properties of Mrp4 are poorly understood so far. This study aims to explore the angiogenic properties of MRP4 in human retinal microvascular endothelial cells (HRECs) utilizing the RNA interference (RNAi) technique. MRP4 expression was decreased at the mRNA and protein levels after stimulation with exogenous vascular endothelial growth factor in a dose-dependent manner. RNAi-mediated MRP4 knockdown in HRECs do not affect cell proliferation but enhances cell migration. Moreover, cell apoptosis induced by serum starvation was less prominent in MRP4 siRNA-treated HRECs as compared to control siRNA-treated HRECs. In a Matrigel-based tube-formation assay, although MRP4 knockdown did not lead to a significant change in the total tube length, MRP4 siRNA-treated HRECs assembled and aggregated into a massive tube-like structure, which was not observed in control siRNA-treated HRECs. These results suggest that MRP4 is uniquely involved in retinal angiogenesis.

  2. Bio-inspired nanocomposite assemblies as smart skin components.

    SciTech Connect (OSTI)

    Montano, Gabriel A.; Xiao, Xiaoyin; Achyuthan, Komandoor E.; Allen, Amy; Brozik, Susan Marie; Edwards, Thayne L.; Frischknecht, Amalie Lucile; Wheeler, David Roger

    2011-09-01T23:59:59.000Z

    There is national interest in the development of sophisticated materials that can automatically detect and respond to chemical and biological threats without the need for human intervention. In living systems, cell membranes perform such functions on a routine basis, detecting threats, communicating with the cell, and triggering automatic responses such as the opening and closing of ion channels. The purpose of this project was to learn how to replicate simple threat detection and response functions within artificial membrane systems. The original goals toward developing 'smart skin' assemblies included: (1) synthesizing functionalized nanoparticles to produce electrochemically responsive systems within a lipid bilayer host matrices, (2) calculating the energetics of nanoparticle-lipid interactions and pore formation, and (3) determining the mechanism of insertion of nanoparticles in lipid bilayers via imaging and electrochemistry. There are a few reports of the use of programmable materials to open and close pores in rigid hosts such as mesoporous materials using either heat or light activation. However, none of these materials can regulate themselves in response to the detection of threats. The strategies we investigated in this project involve learning how to use programmable nanomaterials to automatically eliminate open channels within a lipid bilayer host when 'threats' are detected. We generated and characterized functionalized nanoparticles that can be used to create synthetic pores through the membrane and investigated methods of eliminating the pores either through electrochemistry, change in pH, etc. We also focused on characterizing the behavior of functionalized gold NPs in different lipid membranes and lipid vesicles and coupled these results to modeling efforts designed to gain an understanding of the interaction of nanoparticles within lipid assemblies.

  3. Sensitive Targeted Quantification of ERK Phosphorylation Dynamics and Stoichiometry in Human Cells without Affinity Enrichment

    SciTech Connect (OSTI)

    Shi, Tujin; Gao, Yuqian; Gaffrey, Matthew J.; Nicora, Carrie D.; Fillmore, Thomas L.; Chrisler, William B.; Gritsenko, Marina A.; Wu, Chaochao; He, Jintang; Bloodsworth, Kent J.; Zhao, Rui; Camp, David G.; Liu, Tao; Rodland, Karin D.; Smith, Richard D.; Wiley, H. S.; Qian, Weijun

    2014-12-17T23:59:59.000Z

    Mass spectrometry-based targeted quantification is a promising technology for site-specific quantification of posttranslational modifications (PTMs). However, a major constraint of most targeted MS approaches is the limited sensitivity for quantifying low-abundance PTMs, requiring the use of affinity reagents to enrich specific PTMs. Herein, we demonstrate the direct site-specific quantification of ERK phosphorylation isoforms (pT, pY, pTpY) and their relative stoichiometries using a highly sensitive targeted MS approach termed high-pressure, high-resolution separations with intelligent selection and multiplexing (PRISM). PRISM provides effective enrichment of target peptides within a given fraction from complex biological matrix with minimal sample losses, followed by selected reaction monitoring (SRM) quantification. The PRISM-SRM approach enabled direct quantification of ERK phosphorylation in human mammary epithelial cells (HMEC) from as little as 25 µg tryptic peptides from whole cell lysates. Compared to immobilized metal-ion affinity chromatography, PRISM provided >10-fold improvement in signal intensities, presumably due to the better peptide recovery of PRISM for handling small size samples. This approach was applied to quantify ERK phosphorylation dynamics in HMEC treated by different doses of EGF at both the peak activation (10 min) and steady state (2 h). At 10 min, the maximal ERK activation was observed with 0.3 ng/mL dose, whereas the maximal steady state level of ERK activation at 2 h was at 3 ng/ml dose, corresponding to 1200 and 9000 occupied receptors, respectively. At 10 min, the maximally activated pTpY isoform represented ~40% of total ERK, falling to less than 10% at 2 h. The time course and dose-response profiles of individual phosphorylated ERK isoforms indicated that singly phosphorylated pT-ERK never increases significantly, while the increase of pY-ERK paralleled that of pTpY-ERK. This data supports for a processive, rather than distributed, model of ERK phosphorylation. The PRISM-SRM quantification of protein phosphorylation illustrates the potential for simultaneous quantification of multiple PTMs.

  4. "Skin Cancer-What to Look For" Rochester Recreation

    E-Print Network [OSTI]

    Goldman, Steven A.

    "Skin Cancer- What to Look For" Rochester Recreation Club for the Deaf May 20, 2010 #12;Supporters for the Deaf ("REAP") #12;Overview Skin Overview What is skin cancer? Who is at risk? How common is skin cancer? Signs of skin cancer Prevention Treatments #12;Skin Overview Skin is the largest organ in your body

  5. Induction of apoptosis by esculetin in human leukemia U937 cells through activation of JNK and ERK

    SciTech Connect (OSTI)

    Park, Cheol; Jin, Cheng-Yun [Division of Biological Sciences, College of Natural Science, Pusan National University, Busan 609-735 (Korea, Republic of); Kim, Gi-Young [Faculty of Applied Marine Science, Cheju National University, Jeju Special Self-Governing Province 690-756 (Korea, Republic of); Choi, Il-Whan [Department of Microbiology, College of Medicine and Center for Viral Disease Research, Inje University, Busan 614-735 (Korea, Republic of); Kwon, Taeg Kyu [Department of Immunology, School of Medicine, Keimyung University, Taegu 700-712 (Korea, Republic of); Choi, Byung Tae [Department of Anatomy, Graduate School of Oriental Medicine, Pusan National University, 609-735 (Korea, Republic of); Lee, Su Jae [Department of Chemistry, Hanyang University, Seoul 133-791 (Korea, Republic of); Lee, Won Ho [Division of Biological Sciences, College of Natural Science, Pusan National University, Busan 609-735 (Korea, Republic of); Choi, Yung Hyun [Department of Anatomy, Graduate School of Oriental Medicine, Pusan National University, 609-735 (Korea, Republic of); Department of Biochemistry, Dongeui University College of Oriental Medicine and Department of Biomaterial Control (BK21 program), Dongeui University Graduate School, Busan 614-052 (Korea, Republic of)], E-mail: lab301@nate.com

    2008-03-01T23:59:59.000Z

    Esculetin is a phenolic compound that is found in various natural plant products and induces apoptosis in several types of human cancer cells. However, the underlying mechanisms of its action are not completely understood. In the present study, we used human leukemia cells to gain further insight into the mechanism of esculetin-induced anti-proliferative action and apoptosis. It was found that esculetin inhibits cell viability by inducing apoptosis, as evidenced by the formation of apoptotic bodies, DNA fragmentation, and the accumulation of cells in the sub-G1 phase. Esculetin-induced apoptosis was correlated with mitochondrial dysfunction, leading to the release of cytochrome c from the mitochondria to the cytosol, as well as the proteolytic activation of caspases. The z-DEVD-fmk caspase-3 inhibitor and the ectopic expression of anti-apoptotic Bcl-2 significantly inhibited esculetin-induced apoptosis, demonstrating the important role of caspase-3 and mitochondrial proteins in the observed cytotoxic effect. Furthermore, esculetin selectively increased the phosphorylation of extracellular-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but not that of other kinases such as Akt and p38 activation. In addition, an ERK-specific inhibitor, PD98059, and a JNK-specific inhibitor, SP600125, showed inhibited sub-G1 phase DNA content, DNA fragmentation, caspase activation, and mitochondrial dysfunction induced by esculetin treatment. These results indicated that the JNK and ERK pathways were key regulators of apoptosis in response to esculetin in human leukemia U937 cells.

  6. Structure of the Human Activating Natural Cytotoxicity Receptor NKp30 Bound to its Tumor Cell Ligand B7-H6

    SciTech Connect (OSTI)

    Y Li; Q Wang; R Mariuzza

    2011-12-31T23:59:59.000Z

    Natural killer (NK) cells are lymphocytes of the innate immune system that participate in the elimination of tumor cells. In humans, the activating natural cytotoxicity receptors (NCRs) NKp30, NKp44, and NKp46 play a major role in NK cell-mediated tumor cell lysis. NKp30 recognizes B7-H6, a member of the B7 family which is expressed on tumor, but not healthy, cells. To understand the basis for tumor surveillance by NCRs, we determined the structure of NKp30, a member of the CD28 family which includes CTLA-4 and PD-1, in complex with B7-H6. The overall organization of the NKp30-B7-H6-activating complex differs considerably from those of the CTLA-4-B7 and PD-1-PD-L T cell inhibitory complexes. Whereas CTLA-4 and PD-1 use only the front {beta}-sheet of their Ig-like domain to bind ligands, NKp30 uses both front and back {beta}-sheets, resulting in engagement of B7-H6 via the side, as well as face, of the {beta}-sandwich. Moreover, B7-H6 contacts NKp30 through the complementarity-determining region (CDR) - like loops of its V-like domain in an antibody-like interaction that is not observed for B7 or PD-L. This first structure of an NCR bound to ligand provides a template for designing molecules to stimulate NKp30-mediated cytolytic activity for tumor immunotherapy.

  7. Nickel (II)-induced cytotoxicity and apoptosis in human proximal tubule cells through a ROS- and mitochondria-mediated pathway

    SciTech Connect (OSTI)

    Wang, Yi-Fen; Shyu, Huey-Wen [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China)] [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China); Chang, Yi-Chuang [Department of Nursing, Fooyin University, Kaohsiung, Taiwan (China)] [Department of Nursing, Fooyin University, Kaohsiung, Taiwan (China); Tseng, Wei-Chang [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China)] [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China); Huang, Yeou-Lih [Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China)] [Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Lin, Kuan-Hua; Chou, Miao-Chen; Liu, Heng-Ling [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China)] [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China); Chen, Chang-Yu, E-mail: mt037@mail.fy.edu.tw [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China)] [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China)

    2012-03-01T23:59:59.000Z

    Nickel compounds are known to be toxic and carcinogenic in kidney and lung. In this present study, we investigated the roles of reactive oxygen species (ROS) and mitochondria in nickel (II) acetate-induced cytotoxicity and apoptosis in the HK-2 human renal cell line. The results showed that the cytotoxic effects of nickel (II) involved significant cell death and DNA damage. Nickel (II) increased the generation of ROS and induced a noticeable reduction of mitochondrial membrane potential (MMP). Analysis of the sub-G1 phase showed a significant increase in apoptosis in HK-2 cells after nickel (II) treatment. Pretreatment with N-acetylcysteine (NAC) not only inhibited nickel (II)-induced cell death and DNA damage, but also significantly prevented nickel (II)-induced loss of MMP and apoptosis. Cell apoptosis triggered by nickel (II) was characterized by the reduced protein expression of Bcl-2 and Bcl-xL and the induced the protein expression of Bad, Bcl-Xs, Bax, cytochrome c and caspases 9, 3 and 6. The regulation of the expression of Bcl-2-family proteins, the release of cytochrome c and the activation of caspases 9, 3 and 6 were inhibited in the presence of NAC. These results suggest that nickel (II) induces cytotoxicity and apoptosis in HK-2 cells via ROS generation and that the mitochondria-mediated apoptotic signaling pathway may be involved in the positive regulation of nickel (II)-induced renal cytotoxicity.

  8. Interactions between ultraviolet light and interleukin-1 on MSH binding in both mouse melanoma and human squamous carcinoma cells

    SciTech Connect (OSTI)

    Birchall, N.; Orlow, S.J.; Kupper, T.; Pawelek, J. (Univ. of Auckland, (New Zealand))

    1991-03-29T23:59:59.000Z

    Interactions between beta-melanotropin (MSH), interleukin 1-a (IL-1), and ultraviolet light (UV) were examined in Cloudman S91 mouse melanoma and RHEK human squamous carcinoma cell lines. The following points were established: (1) both cell lines produced IL-1 and their production was stimulated by exposure of the cells to UV; (2) both cell lines possessed high affinity binding sites for MSH, and their ability to bind MSH was modulated by IL-1; (3) IL-1 exhibited both stimulatory and inhibitory effects on MSH binding to Cloudman cells; and (4) the stimulatory effect of IL-1 on MSH binding to melanoma cells was reflected in enhanced cellular responsiveness to MSH regarding tyrosinase activity (E.C. 1.14.18.1) and melanin content. The findings raise the possibility that interactions between keratinocytes and melanocytes may be regulated by IL-1 and MSH, and suggest a possible mechanism for stimulation of cutaneous melanogenesis by solar radiation: enhancement of MSH receptor activity by induction of IL-1.

  9. Dissecting Biological Dark Matter: Single Cell Genetic Analysis of TM7, a Rare and Uncultivated Microbe from the Human Mouth

    SciTech Connect (OSTI)

    Fenner, Marsha W; Marcy, Yann; Ouverney, Cleber; Bik, Elisabeth M.; Losekann, Tina; Ivanova, Natalia; Martin, H. Garcia; Szeto, E.; Platt, Darren; Hugenholtz, Philip; Relman, David A.; Quake, Stephen R.

    2007-07-01T23:59:59.000Z

    We have developed a microfluidic device that allows the isolation and genome amplification of individual microbial cells, thereby enabling organism-level genomic analysis of complex microbial ecosystems without the need for culture. This device was used to perform a directed survey of the human subgingival crevice and to isolate bacteria having rod-like morphology. Several isolated microbes had a 16S rRNA sequence that placed them in candidate phylum TM7, which has no cultivated or sequenced members. Genome amplification from individual TM7 cells allowed us to sequence and assemble >1,000 genes, providing insight into the physiology of members of this phylum. This approach enables single-cell genetic analysis of any uncultivated minority member of a microbial community.

  10. TGF{beta}-mediated formation of pRb-E2F complexes in human myeloid leukemia cells

    SciTech Connect (OSTI)

    Hu Xiaotang [School of Natural and Health Science, Barry University, 11300 Northeast Second Avenue, Miami Shores, FL 33161 (United States)], E-mail: xthu@mail.barry.edu

    2008-05-02T23:59:59.000Z

    TGF{beta} is well known for its inhibitory effect on cell cycle G1 checkpoint kinases. However, its role in the control of pRb-E2F complexes is not well established. TGF{beta} inhibits phosphorylation of pRb at several serine and threonine residues and regulates the association of E2F transcription factors with pRb family proteins. Recent studies found that predominantly E2F-4, p130, and histone deacetylase (HDAC) are found to bind to corresponding E2F-responsive promoters in G0/G1 phase. As cells progress through mid-G1, p130-E2F4 complex are replaced by p107-E2F4 followed by activators E2F1, 2, and 3. pRb was not detectable in the promoters containing the E2F-responsive site in cycling cells but was associated with E2F4-p130 complexes or E2F4-p107 complexes during G0/G1 phase. In human myeloid leukemia cell line, MV4-11, TGF{beta} upregulated pRb-E2F-4 and p130-E2F-4, and downregulated p107-E2F-4 complexes. However, pRB-E2F1 and pRb-E2F3 complexes were found in proliferating cells but not in TGF{beta} arrested G1 cells. In addition, electrophoretic gel mobility shift assay (EMSA) could not detect pRb-E2F DNA-binding activities either in S or G1 phase but exhibited the existence of p107-E2F4 in proliferating cells and p130-E2F4 complexes in TGF{beta}-arrested G1 cells, respectively. Our data suggest that p107 and p130, but not pRb, and the repressor E2F, but not activator E2Fs, play a critical role in regulating E2F-responsive gene expression in TGF{beta}-mediated cell cycle control in human myeloid leukemia cells.

  11. Modulation of dendritic cells by human neutrophil elastase and its inhibitors in pulmonary inflammation 

    E-Print Network [OSTI]

    Roghanian, Ali

    2007-01-01T23:59:59.000Z

    Dendritic cells (DC) are sentinels of the immune system that display an extraordinary capacity to present antigen to naïve T cells and initiate immune responses. DCs are distributed throughout the lungs in the conducting ...

  12. LET dependence of radiation-induced bystander effects using human prostate tumor cells

    E-Print Network [OSTI]

    Anzenberg, Vered

    2008-01-01T23:59:59.000Z

    In the past fifteen years, evidence provided by many independent research groups have indicated higher numbers of cells exhibiting damage than expected based on the number of cells traversed by the radiation. This phenomenon ...

  13. Stress-specific signatures: expression profiling of p53 wild-type and -null human cells

    E-Print Network [OSTI]

    stress on the protein folding apparatus of the cell, and results in the induction of molecular chaperones

  14. Glycogen synthase kinase 3 regulates PAX3-FKHR-mediated cell proliferation in human alveolar rhabdomyosarcoma cells

    SciTech Connect (OSTI)

    Zeng, Fu-Yue; Dong, Hanqing; Cui, Jimmy; Liu, Lingling [Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105 (United States)] [Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105 (United States); Chen, Taosheng, E-mail: taosheng.chen@stjude.org [Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105 (United States)] [Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105 (United States)

    2010-01-01T23:59:59.000Z

    Patients with alveolar rhabdomyosarcoma (ARMS) have poorer response to conventional chemotherapy and lower survival rates than those with embryonal RMS (ERMS). To identify compounds that preferentially block the growth of ARMS, we conducted a small-scale screen of 160 kinase inhibitors against the ARMS cell line Rh30 and ERMS cell line RD and identified inhibitors of glycogen synthase kinase 3 (GSK3), including TWS119 as ARMS-selective inhibitors. GSK3 inhibitors inhibited cell proliferation and induced apoptosis more effectively in Rh30 than RD cells. Ectopic expression of fusion protein PAX3-FKHR in RD cells significantly increased their sensitivity to TWS119. Down-regulation of GSK3 by GSK3 inhibitors or siRNA significantly reduced the transcriptional activity of PAX3-FKHR. These results suggest that GSK3 is directly involved in regulating the transcriptional activity of PAX3-FKHR. Also, GSK3 phosphorylated PAX3-FKHR in vitro, suggesting that GSK3 might regulate PAX3-FKHR activity via phosphorylation. These findings support a novel mechanism of PAX3-FKHR regulation by GSK3 and provide a novel strategy to develop GSK inhibitors as anti-ARMS therapies.

  15. Lasers in Surgery and Medicine 28:113120 (2001) Inuence of Nozzle-to-Skin Distance in Cryogen Spray

    E-Print Network [OSTI]

    Aguilar, Guillermo

    2001-01-01T23:59:59.000Z

    of dis- tance from the nozzle tip. Results: Size of spray cones and sprayed areas vary with distanceLasers in Surgery and Medicine 28:113±120 (2001) In¯uence of Nozzle-to-Skin Distance in Cryogen, the optimal atomizing nozzle design and operating conditions for cooling human skin remain to be determined

  16. Antiproliferative MCR peptides block physical interaction of insulin with retinoblastoma protein (RB) in human lung cancer cells

    E-Print Network [OSTI]

    Razvan Tudor Radulescu; Kai Kehe

    2007-06-13T23:59:59.000Z

    Fifteen years ago, a structural analysis of the hormone insulin and the retinoblastoma tumor suppressor protein (RB) revealed that they may physically interact with one another. Subsequently, an RB peptide corresponding to the proposed RB binding site for insulin was found to recognize full-length insulin in vitro. As part of efforts aimed at developing this RB peptide into an anti-cancer drug, this molecule was chemically coupled to a cellular internalization signal and termed "MCR peptide". Meanwhile, several such MCR peptide variants have been demonstrated to restrain the proliferation of different human cancer cells in vitro and in vivo. Moreover, one of the MCR peptides coined MCR-10 was shown to be capable of interfering with the complex formation between insulin and RB in HepG2 human hepatoma cells, as monitored by immunofluorescence. This latter result indicating an in vivo association between insulin and RB was confirmed by a follow-up study combining the methods of co-immunoprecipitation and immunoblotting. Here, we provide evidence for the existence of the insulin-RB complex in A549 human non-small cell lung cancer cells. Specifically, we demonstrate this heterodimer by means of a magnetic beads-based immunoprecipitation approach and equally show that this dimer can be disrupted by MCR-4 or MCR-10 each of which is known to possess antiproliferative properties, yet to a much lesser extent by a control peptide. Thus, this investigation has yielded another important proof for the occurrence of the insulin-RB dimer and, furthermore, its validity as a target for antineoplastic MCR peptides.

  17. The protein pheromone Er-1 of the ciliate Euplotes raikovi stimulates human T-cell activity: Involvement of interleukin-2 system

    SciTech Connect (OSTI)

    Cervia, Davide, E-mail: d.cervia@unitus.it [Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), University of Tuscia, Viterbo (Italy) [Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), University of Tuscia, Viterbo (Italy); Department of Biomedical and Clinical Sciences, “Luigi Sacco” University Hospital, University of Milan, Milano (Italy); Catalani, Elisabetta; Belardinelli, Maria Cristina [Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), University of Tuscia, Viterbo (Italy)] [Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), University of Tuscia, Viterbo (Italy); Perrotta, Cristiana [Department of Biomedical and Clinical Sciences, “Luigi Sacco” University Hospital, University of Milan, Milano (Italy)] [Department of Biomedical and Clinical Sciences, “Luigi Sacco” University Hospital, University of Milan, Milano (Italy); Picchietti, Simona [Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), University of Tuscia, Viterbo (Italy)] [Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), University of Tuscia, Viterbo (Italy); Alimenti, Claudio [Department of Environmental and Natural Sciences, University of Camerino, Camerino (Italy)] [Department of Environmental and Natural Sciences, University of Camerino, Camerino (Italy); Casini, Giovanni; Fausto, Anna Maria [Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), University of Tuscia, Viterbo (Italy)] [Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), University of Tuscia, Viterbo (Italy); Vallesi, Adriana [Department of Environmental and Natural Sciences, University of Camerino, Camerino (Italy)] [Department of Environmental and Natural Sciences, University of Camerino, Camerino (Italy)

    2013-02-01T23:59:59.000Z

    Water-soluble protein signals (pheromones) of the ciliate Euplotes have been supposed to be functional precursors of growth factors and cytokines that regulate cell–cell interaction in multi-cellular eukaryotes. This work provides evidence that native preparations of the Euplotes raikovi pheromone Er-1 (a helical protein of 40 amino acids) specifically increases viability, DNA synthesis, proliferation, and the production of interferon-?, tumor necrosis factor-?, interleukin (IL)-1?, IL-2, and IL-13 in human Jurkat T-cells. Also, Er-1 significantly decreases the mRNA levels of the ? and ? subunits of IL-2 receptor (IL-2R), while the mRNA levels of the ? subunit appeared to be not affected. Jurkat T-cell treatments with Er-1 induced the down-regulation of the IL-2R? subunit by a reversible and time-dependent endocytosis, and increased the levels of phosphorylation of the extracellular signal-regulated kinases (ERK). The cell-type specificity of these effects was supported by the finding that Er-1, although unable to directly influence the growth of human glioma U-373 cells, induced Jurkat cells to synthesize and release factors that, in turn, inhibited the U-373 cell proliferation. Overall, these findings imply that Er-1 coupling to IL-2R and ERK immuno-enhances T-cell activity, and that this effect likely translates to an inhibition of glioma cell growth. -- Highlights: ? Euplotes pheromone Er-1 increases the growth of human Jurkat T-cells. ? Er-1 increases the T-cell production of specific cytokines. ? Er-1 activates interleukin-2 receptor and extracellular signal-regulated kinases. ? The immuno-enhancing effect of Er-1 on Jurkat cells translates to an inhibition of human glioma cell growth.

  18. Characterization of cancer stem cell properties of CD24 and CD26-positive human malignant mesothelioma cells

    SciTech Connect (OSTI)

    Yamazaki, Hiroto; Naito, Motohiko; Ghani, Farhana Ishrat [Division of Clinical Immunology, Institute of Medical Science, University of Tokyo, Tokyo (Japan)] [Division of Clinical Immunology, Institute of Medical Science, University of Tokyo, Tokyo (Japan); Dang, Nam H. [Division of Hematology/Oncology, University of Florida Shands Cancer Center, Gainesville, FL 32610 (United States)] [Division of Hematology/Oncology, University of Florida Shands Cancer Center, Gainesville, FL 32610 (United States); Iwata, Satoshi [Division of Clinical Immunology, Institute of Medical Science, University of Tokyo, Tokyo (Japan)] [Division of Clinical Immunology, Institute of Medical Science, University of Tokyo, Tokyo (Japan); Morimoto, Chikao, E-mail: morimoto@ims.u-tokyo.ac.jp [Division of Clinical Immunology, Institute of Medical Science, University of Tokyo, Tokyo (Japan)] [Division of Clinical Immunology, Institute of Medical Science, University of Tokyo, Tokyo (Japan)

    2012-03-16T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer We focused on CD24 and CD26 for further analysis of CSC properties in MM. Black-Right-Pointing-Pointer Their expressions were correlated with chemoresistance, cell growth, and invasion. Black-Right-Pointing-Pointer Their expressions were also correlated with several cancer related genes. Black-Right-Pointing-Pointer The expression of each marker was correlated with different CSC property in Meso1. Black-Right-Pointing-Pointer Phosphorylation of ERK by EGF was regulated by expression of CD26, but not CD24. -- Abstract: Malignant mesothelioma (MM) is an asbestos-related malignancy characterized by rapid growth and poor prognosis. In our previous study, we have demonstrated that several cancer stem cell (CSC) markers correlated with CSC properties in MM cells. Among these markers, we focused on two: CD24, the common CSC marker, and CD26, the additional CSC marker. We further analyzed the CSC properties of CD24 and CD26-positve MM cells. We established RNAi-knockdown cells and found that these markers were significantly correlated with chemoresistance, proliferation, and invasion potentials in vitro. Interestingly, while Meso-1 cells expressed both CD24 and CD26, the presence of each of these two markers was correlated with different CSC property. In addition, downstream signaling of these markers was explored by microarray analysis, which revealed that their expressions were correlated with several cancer-related genes. Furthermore, phosphorylation of ERK by EGF stimulation was significantly affected by the expression of CD26, but not CD24. These results suggest that CD24 and CD26 differentially regulate the CSC potentials of MM and could be promising targets for CSC-oriented therapy.

  19. Comparison of the Effects of Carbon Ion and Photon Irradiation on the Angiogenic Response in Human Lung Adenocarcinoma Cells

    SciTech Connect (OSTI)

    Kamlah, Florentine, E-mail: Kamlah@staff.uni-marburg.de [Department of Radiotherapy and Radiooncology, Philipps-University, Marburg (Germany); Haenze, Joerg [Department of Urology and Pediatric Urology, Philipps-University, Marburg (Germany); Arenz, Andrea [Department of Radiotherapy and Radiooncology, Philipps-University, Marburg (Germany); Seay, Ulrike; Hasan, Diya [Department of Internal Medicine II/V, Justus-Liebig-University, Giessen (Germany); Juricko, Janko; Bischoff, Birgit [Department of Radiotherapy and Radiooncology, Philipps-University, Marburg (Germany); Gottschald, Oana R. [Department of Internal Medicine II/V, Justus-Liebig-University, Giessen (Germany); Fournier, Claudia; Taucher-Scholz, Gisela; Scholz, Michael [GSI Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany); Seeger, Werner [Department of Internal Medicine II/V, Justus-Liebig-University, Giessen (Germany); Engenhart-Cabillic, Rita [Department of Radiotherapy and Radiooncology, Philipps-University, Marburg (Germany); Department of Radiotherapy, Justus-Liebig-University, Giessen (Germany); Rose, Frank [Department of Radiotherapy and Radiooncology, Philipps-University, Marburg (Germany)

    2011-08-01T23:59:59.000Z

    Purpose: Radiotherapy resistance is a commonly encountered problem in cancer treatment. In this regard, stabilization of endothelial cells and release of angiogenic factors by cancer cells contribute to this problem. In this study, we used human lung adenocarcinoma (A549) cells to compare the effects of carbon ion and X-ray irradiation on the cells' angiogenic response. Methods and Materials: A549 cells were irradiated with biologically equivalent doses for cell survival of either carbon ions (linear energy transfer, 170 keV/{mu}m; energy of 9.8 MeV/u on target) or X-rays and injected with basement membrane matrix into BALB/c nu/nu mice to generate a plug, allowing quantification of angiogenesis by blood vessel enumeration. The expression of angiogenic factors (VEGF, PlGF, SDF-1, and SCF) was assessed at the mRNA and secreted protein levels by using real-time reverse transcription-PCR and enzyme-linked immunosorbent assay. Signal transduction mediated by stem cell factor (SCF) was assessed by phosphorylation of its receptor c-Kit. For inhibition of SCF/c-Kit signaling, a specific SCF/c-Kit inhibitor (ISCK03) was used. Results: Irradiation of A549 cells with X-rays (6 Gy) but not carbon ions (2 Gy) resulted in a significant increase in blood vessel density (control, 20.71 {+-} 1.55; X-ray, 36.44 {+-} 3.44; carbon ion, 16.33 {+-} 1.03; number per microscopic field). Concordantly, irradiation with X-rays but not with carbon ions increased the expression of SCF and subsequently caused phosphorylation of c-Kit in endothelial cells. ISCK03 treatment of A549 cells irradiated with X-rays (6 Gy) resulted in a significant decrease in blood vessel density (X-ray, 36.44 {+-} 3.44; X-ray and ISCK03, 4.33 {+-} 0.71; number of microscopic field). These data indicate that irradiation of A549 cells with X-rays but not with carbon ions promotes angiogenesis. Conclusions: The present study provides evidence that SCF is an X-ray-induced mediator of angiogenesis in A549 cells, a phenomenon that could not be observed with carbon ion irradiation. Thus, in this model system evaluating angiogenesis, carbon ion irradiation may have a therapeutic advantage. This observation should be confirmed in orthotopic lung tumor models.

  20. Turbine vane with high temperature capable skins

    DOE Patents [OSTI]

    Morrison, Jay A. (Oviedo, FL)

    2012-07-10T23:59:59.000Z

    A turbine vane assembly includes an airfoil extending between an inner shroud and an outer shroud. The airfoil can include a substructure having an outer peripheral surface. At least a portion of the outer peripheral surface is covered by an external skin. The external skin can be made of a high temperature capable material, such as oxide dispersion strengthened alloys, intermetallic alloys, ceramic matrix composites or refractory alloys. The external skin can be formed, and the airfoil can be subsequently bi-cast around or onto the skin. The skin and the substructure can be attached by a plurality of attachment members extending between the skin and the substructure. The skin can be spaced from the outer peripheral surface of the substructure such that a cavity is formed therebetween. Coolant can be supplied to the cavity. Skins can also be applied to the gas path faces of the inner and outer shrouds.

  1. Adenoviral Mediated Gene Delivery to Human Umbilical Cord Mesenchymal Stromal Cells for Inner Ear Hair Cell Differentiation

    E-Print Network [OSTI]

    Devarajan, Keerthana

    2011-07-28T23:59:59.000Z

    . Sensory neural hearing loss (SNHL) is the most common form, which results from degeneration of inner ear sensory hair cells and auditory neurons in the cochlea. In recent years, there has been an increasing interest in gene delivery to mesenchymal stem...

  2. NON-MELANOMA SKIN CANCER 3. NON-MELANOMA SKIN CANCER

    E-Print Network [OSTI]

    Paxton, Anthony T.

    NON-MELANOMA SKIN CANCER 21 3. NON-MELANOMA SKIN CANCER 3.1. SUMMARY Non-melanoma skin cancer (NMSC their cancer diagnosis. Table 3.1 Summary information for non-melanoma skin cancer in Ireland, 1995 number of cases for both sexes presented in the 70­79 age group. Figure 3.1 Age distribution of non-melanoma

  3. Overexpression of IRS2 in isolated pancreatic islets causes proliferation and protects human {beta}-cells from hyperglycemia-induced apoptosis

    SciTech Connect (OSTI)

    Mohanty, S. [Division of Endocrinology and Diabetes, University Hospital of Zurich, 8091 Zurich (Switzerland); Spinas, G.A. [Division of Endocrinology and Diabetes, University Hospital of Zurich, 8091 Zurich (Switzerland); Maedler, K. [Division of Endocrinology and Diabetes, University Hospital of Zurich, 8091 Zurich (Switzerland); Zuellig, R.A. [Division of Endocrinology and Diabetes, University Hospital of Zurich, 8091 Zurich (Switzerland); Lehmann, R. [Division of Endocrinology and Diabetes, University Hospital of Zurich, 8091 Zurich (Switzerland); Donath, M.Y. [Division of Endocrinology and Diabetes, University Hospital of Zurich, 8091 Zurich (Switzerland); Trueb, T. [Universitaetsverwaltung, Stab fuer Sachmittel-Kredite, KUN110, Kuenstlergasse 15, 8001 Zurich (Switzerland); Niessen, M. [Division of Endocrinology and Diabetes, University Hospital of Zurich, 8091 Zurich (Switzerland)]. E-mail: markus.niessen@usz.ch

    2005-02-01T23:59:59.000Z

    Studies in vivo indicate that IRS2 plays an important role in maintaining functional {beta}-cell mass. To investigate if IRS2 autonomously affects {beta}-cells, we have studied proliferation, apoptosis, and {beta}-cell function in isolated rat and human islets after overexpression of IRS2 or IRS1. We found that {beta}-cell proliferation was significantly increased in rat islets overexpressing IRS2 while IRS1 was less effective. Moreover, proliferation of a {beta}-cell line, INS-1, was decreased after repression of Irs2 expression using RNA oligonucleotides. Overexpression of IRS2 in human islets significantly decreased apoptosis of {beta}-cells, induced by 33.3 mM D-glucose. However, IRS2 did not protect cultured rat islets against apoptosis in the presence of 0.5 mM palmitic acid. Overexpression of IRS2 in isolated rat islets significantly increased basal and D-glucose-stimulated insulin secretion as determined in perifusion experiments. Therefore, IRS2 is sufficient to induce proliferation in rat islets and to protect human {beta}-cells from D-glucose-induced apoptosis. In addition, IRS2 can improve {beta}-cell function. Our results indicate that IRS2 acts autonomously in {beta}-cells in maintenance and expansion of functional {beta}-cell mass in vivo.

  4. Targeting miR-21 enhances the sensitivity of human colon cancer HT-29 cells to chemoradiotherapy in vitro

    SciTech Connect (OSTI)

    Deng, Jun; Lei, Wan; Fu, Jian-Chun; Zhang, Ling; Li, Jun-He; Xiong, Jian-Ping, E-mail: jpxiong@medmail.com.cn

    2014-01-17T23:59:59.000Z

    Highlight: •MiR-21 plays a significant role in 5-FU resistance. •This role might be attributed to targeting of hMSH2 as well as TP and DPD via miR-21 targeted hMSH2. •Indirectly targeted TP and DPD to influence 5-FU chemotherapy sensitivity. -- Abstract: 5-Fluorouracil (5-FU) is a classic chemotherapeutic drug that has been widely used for colorectal cancer treatment, but colorectal cancer cells are often resistant to primary or acquired 5-FU therapy. Several studies have shown that miR-21 is significantly elevated in colorectal cancer. This suggests that this miRNA might play a role in this resistance. In this study, we investigated this possibility and the possible mechanism underlying this role. We showed that forced expression of miR-21 significantly inhibited apoptosis, enhanced cell proliferation, invasion, and colony formation ability, promoted G1/S cell cycle transition and increased the resistance of tumor cells to 5-FU and X radiation in HT-29 colon cancer cells. Furthermore, knockdown of miR-21 reversed these effects on HT-29 cells and increased the sensitivity of HT-29/5-FU to 5-FU chemotherapy. Finally, we showed that miR-21 targeted the human mutS homolog2 (hMSH2), and indirectly regulated the expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). These results demonstrate that miR-21 may play an important role in the 5-FU resistance of colon cancer cells.

  5. Latent infection of myeloid progenitors by human cytomegalovirus protects cells from FAS-mediated apoptosis through the cellular IL-10/PEA15 pathway

    E-Print Network [OSTI]

    Poole, Emma; Lau, Jonathan; Sinclair, John

    2015-05-08T23:59:59.000Z

    ., Breidenstein, A. & Compton, T. (2012). Human cytomegalovirus activation of ERK 214 and myeloid cell leukemia-1 protein correlates with survival of latently infected cells. Proc 215 Natl Acad Sci U S A 109, 588-593. 216 Reeves, M. B., MacAry, P. A., Lehner, P...

  6. Soft inertial microfluidics for high throughput separation of bacteria from human blood cells

    E-Print Network [OSTI]

    Wu, Zhigang

    2009-01-01T23:59:59.000Z

    Soft inertial microfluidics for high throughput separation1 Introduction Microfluidics has gained significant advancesof mammalian cells using microfluidics 3,4 , there have been

  7. Discovery of Human sORF-Encoded Polypeptides (SEPs) in Cell Lines and Tissue

    E-Print Network [OSTI]

    Ma, Jiao

    The existence of nonannotated protein-coding human short open reading frames (sORFs) has been revealed through the direct detection of their sORF-encoded polypeptide (SEP) products. The discovery of novel SEPs increases ...

  8. Genetic Background Modulates Gene Expression Profile Induced by Skin Irradiation in Ptch1 Mice

    SciTech Connect (OSTI)

    Galvan, Antonella; Noci, Sara [Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale Tumori, Milan (Italy); Mancuso, Mariateresa; Pazzaglia, Simonetta; Saran, Anna [ENEA Laboratories, Rome (Italy); Dragani, Tommaso A. [Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale Tumori, Milan (Italy)], E-mail: tommaso.dragani@istitutotumori.mi.it

    2008-12-01T23:59:59.000Z

    Purpose: Ptch1 germ-line mutations in mice predispose to radiation-induced basal cell carcinoma of the skin, with tumor incidence modulated by the genetic background. Here, we examined the possible mechanisms underlying skin response to radiation in F1 progeny of Ptch1{sup neo67/+} mice crossed with either skin tumor-susceptible (Car-S) or -resistant (Car-R) mice and X-irradiated (3 Gy) at 2 days of age or left untreated. Methods and Materials: We conducted a gene expression profile analysis in mRNA samples extracted from the skin of irradiated or control mice, using Affymetrix whole mouse genome expression array. Confirmation of the results was done using real-time reverse-transcriptase polymerase chain reaction. Results: Analysis of the gene expression profile of normal skin of F1 mice at 4 weeks of age revealed a similar basal profile in the nonirradiated mice, but alterations in levels of 71 transcripts in irradiated Ptch1{sup neo67/+} mice of the Car-R cross and modulation of only eight genes in irradiated Ptch1{sup neo67/+} mice of the Car-S cross. Conclusions: These results indicate that neonatal irradiation causes a persistent change in the gene expression profile of the skin. The tendency of mice genetically resistant to skin tumorigenesis to show a more complex pattern of transcriptional response to radiation than do genetically susceptible mice suggests a role for this response in genetic resistance to basal cell tumorigenesis.

  9. 5-Methoxyflavanone induces cell cycle arrest at the G2/M phase, apoptosis and autophagy in HCT116 human colon cancer cells

    SciTech Connect (OSTI)

    Shin, Soon Young [SMART Institute of Advanced Biomedical Science, Konkuk University Medical Center, Seoul 143-701 (Korea, Republic of); Department of Biomedical Science and Technology, Research Center for Transcription Control, Konkuk University, Seoul 143-701 (Korea, Republic of); Hyun, Jiye [Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 143-701 (Korea, Republic of); Yu, Jae-Ran [Department of Environmental and Tropical Medicine, Konkuk University School of Medicine, Seoul 143-701 (Korea, Republic of); Lim, Yoongho, E-mail: yoongho@konkuk.ac.kr [Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 143-701 (Korea, Republic of); Lee, Young Han, E-mail: yhlee58@konkuk.ac.kr [SMART Institute of Advanced Biomedical Science, Konkuk University Medical Center, Seoul 143-701 (Korea, Republic of); Department of Biomedical Science and Technology, Research Center for Transcription Control, Konkuk University, Seoul 143-701 (Korea, Republic of)

    2011-08-01T23:59:59.000Z

    Natural flavonoids have diverse pharmacological activities, including anti-oxidative, anti-inflammatory, and anti-cancer activities. In this study, we investigated the molecular mechanism underlying the action of 5-methoxyflavanone (5-MF) which has a strong bioavailability and metabolic stability. Our results show that 5-MF inhibited the growth and clonogenicity of HCT116 human colon cancer cells, and that it activated DNA damage responses, as revealed by the accumulation of p53 and the phosphorylation of DNA damage-sensitive proteins, including ataxia-telangiectasia mutated (ATM) at Ser1981, checkpoint kinase 2 (Chk2) at Thr68, and histone H2AX at Ser139. 5-MF-induced DNA damage was confirmed in a comet tail assay. We also found that 5-MF increased the cleavage of caspase-2 and -7, leading to the induction of apoptosis. Pretreatment with the ATM inhibitor KU55933 enhanced 5-MF-induced {gamma}-H2AX formation and caspase-7 cleavage. HCT116 cells lacking p53 (p53{sup -/-}) or p21 (p21{sup -/-}) exhibited increased sensitivity to 5-MF compared to wild-type cells. 5-MF further induced autophagy via an ERK signaling pathway. Blockage of autophagy with the MEK inhibitor U0126 potentiated 5-MF-induced {gamma}-H2AX formation and caspase-2 activation. These results suggest that a caspase-2 cascade mediates 5-MF-induced anti-tumor activity, while an ATM/Chk2/p53/p21 checkpoint pathway and ERK-mediated autophagy act as a survival program to block caspase-2-mediated apoptosis induced by 5-MF. - Graphical abstract: Display Omitted Highlights: > 5-MF inhibits the proliferation of HCT116 colon cancer cells. > 5-MF inhibits cell cycle progression and induces apoptosis. > Inhibition of autophagy triggers 5-MF-induced apoptosis. > Inhibition of ERK signaling blocks 5-MF-induced autophagy but activates apoptosis. > Treatment with 5-MF in combination with an ERK inhibitor may be a potential therapeutic strategy in human colon cancer.

  10. Nickel compounds induce apoptosis in human bronchial epithelial Beas-2B cells by activation of c-Myc through ERK pathway

    SciTech Connect (OSTI)

    Li Qin; Suen, T.-C.; Sun Hong; Arita, Adriana [New York University School of Medicine, Nelson Institute of Environmental Medicine, 57 Old Forge Road, NY 10987 (United States); Costa, Max [New York University School of Medicine, Nelson Institute of Environmental Medicine, 57 Old Forge Road, NY 10987 (United States)], E-mail: max.costa@nyumc.org

    2009-03-01T23:59:59.000Z

    Nickel compounds are carcinogenic to humans and have been shown to alter epigenetic homeostasis. The c-Myc protein controls 15% of human genes and it has been shown that fluctuations of c-Myc protein alter global epigenetic marks. Therefore, the regulation of c-Myc by nickel ions in immortalized but not tumorigenic human bronchial epithelial Beas-2B cells was examined in this study. It was found that c-Myc protein expression was increased by nickel ions in non-tumorigenic Beas-2B and human keratinocyte HaCaT cells. The results also indicated that nickel ions induced apoptosis in Beas-2B cells. Knockout of c-Myc and its restoration in a rat cell system confirmed the essential role of c-Myc in nickel ion-induced apoptosis. Further studies in Beas-2B cells showed that nickel ion increased the c-Myc mRNA level and c-Myc promoter activity, but did not increase c-Myc mRNA and protein stability. Moreover, nickel ion upregulated c-Myc in Beas-2B cells through the MEK/ERK pathway. Collectively, the results demonstrate that c-Myc induction by nickel ions occurs via an ERK-dependent pathway and plays a crucial role in nickel-induced apoptosis in Beas-2B cells.

  11. Inhibiting the Aurora B Kinase Potently Suppresses Repopulation During Fractionated Irradiation of Human Lung Cancer Cell Lines

    SciTech Connect (OSTI)

    Sak, Ali, E-mail: ali.sak@uni-due.de [Department of Radiotherapy, West German Cancer Centre (WTZ), University Hospital Essen, University Duisburg-Essen, Essen (Germany)] [Department of Radiotherapy, West German Cancer Centre (WTZ), University Hospital Essen, University Duisburg-Essen, Essen (Germany); Stuschke, Martin; Groneberg, Michael; Kuebler, Dennis; Poettgen, Christoph [Department of Radiotherapy, West German Cancer Centre (WTZ), University Hospital Essen, University Duisburg-Essen, Essen (Germany)] [Department of Radiotherapy, West German Cancer Centre (WTZ), University Hospital Essen, University Duisburg-Essen, Essen (Germany); Eberhardt, Wilfried E.E. [Department of Medicine (Cancer Research), West German Cancer Centre (WTZ), University Hospital Essen, University Duisburg-Essen, Essen (Germany)] [Department of Medicine (Cancer Research), West German Cancer Centre (WTZ), University Hospital Essen, University Duisburg-Essen, Essen (Germany)

    2012-10-01T23:59:59.000Z

    Purpose: The use of molecular-targeted agents during radiotherapy of non-small-cell lung cancer (NSCLC) is a promising strategy to inhibit repopulation, thereby improving therapeutic outcome. We assessed the combined effectiveness of inhibiting Aurora B kinase and irradiation on human NSCLC cell lines in vitro. Methods and Materials: NSCLC cell lines were exposed to concentrations of AZD1152-hydroxyquinazoline pyrazol anilide (AZD1152-HQPA) inhibiting colony formation by 50% (IC50{sub clone}) in combination with single dose irradiation or different fractionation schedules using multiple 2-Gy fractions per day up to total doses of 4-40 Gy. The total irradiation dose required to control growth of 50% of the plaque monolayers (TCD50) was determined. Apoptosis, G2/M progression, and polyploidization were also analyzed. Results: TCD50 values after single dose irradiation were similar for the H460 and H661 cell lines with 11.4 {+-} 0.2 Gy and 10.7 {+-} 0.3 Gy, respectively. Fractionated irradiation using 3 Multiplication-Sign 2 Gy/day, 2 Multiplication-Sign 2 Gy/day, and 1 Multiplication-Sign 2 Gy/day schedules significantly increased TCD50 values for both cell lines grown as plaque monolayers with increasing radiation treatment time. This could be explained by a repopulation effect per day that counteracts 75 {+-} 8% and 27 {+-} 6% of the effect of a 2-Gy fraction in H460 and H661 cells, respectively. AZD1152-HQPA treatment concomitant to radiotherapy significantly decreased the daily repopulation effect (H460: 28 {+-} 5%, H661: 10 {+-} 4% of a 2-Gy fraction per day). Treatment with IC50{sub clone} AZD1152-HPQA did not induce apoptosis, prolong radiation-induced G2 arrest, or delay cell cycle progression before the spindle check point. However, polyploidization was detected, especially in cell lines without functional p53. Conclusions: Inhibition of Aurora B kinase with low AZD1152-HQPA concentrations during irradiation of NSCLC cell lines affects repopulation during radiotherapy. Thus, concomitant Aurora B kinase inhibition and irradiation may be a promising strategy for fast repopulating tumors, which are difficult to cure by dose escalation based on conventional fractionation.

  12. Cytotoxicity and inhibitory effects of low-concentration triclosan on adipogenic differentiation of human mesenchymal stem cells

    SciTech Connect (OSTI)

    Guo, Li-Wu [Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States)] [Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States); Wu, Qiangen [Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States)] [Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States); Green, Bridgett; Nolen, Greg [Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States)] [Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States); Shi, Leming [Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States)] [Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States); LoSurdo, Jessica [Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892 (United States)] [Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892 (United States); Deng, Helen [Arkansas Department of Health, Little Rock, AR 72205 (United States)] [Arkansas Department of Health, Little Rock, AR 72205 (United States); Bauer, Steven [Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892 (United States)] [Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892 (United States); Fang, Jia-Long, E-mail: jia-long.fang@fda.hhs.gov [Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States)] [Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States); Ning, Baitang, E-mail: baitang.ning@fda.hhs.gov [Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States)] [Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States)

    2012-07-15T23:59:59.000Z

    Humans at all ages are continually exposed to triclosan (TCS), a widely used antimicrobial agent that can be found in many daily hygiene products, such as toothpastes and shampoos; however, the toxicological and biological effects of TCS in the human body after long-term and low-concentration exposure are far from being well understood. In the current study, we investigated the effects of TCS on the differentiation of human mesenchymal stem cells (hMSCs) by measuring the cytotoxicity, morphological changes, lipid accumulation, and the expression of adipocyte differentiation biomarkers during 21-day adipogenesis. Significant cytotoxicity was observed in un-induced hMSCs treated with high-concentration TCS (? 5.0 ?M TCS), but not with low-concentration treatments (? 2.5 ?M TCS). TCS inhibited adipocyte differentiation of hMSCs in a concentration-dependent manner in the 0.156 to 2.5 ?M range as indicated by morphological changes with Oil Red O staining, which is an index of lipid accumulation. The inhibitory effect was confirmed by a decrease in gene expression of specific adipocyte differentiation biomarkers including adipocyte protein 2, lipoprotein lipase, and adiponectin. Our study demonstrates that TCS inhibits adipocyte differentiation of hMSCs under concentrations that are not cytotoxic and in the range observed in human blood. -- Highlights: ? TCS is cytotoxic to un-induced hMSCs at concentrations ? 5.0 ?M. ? TCS at concentrations ? 2.5 ?M is not cytotoxic to induced hMSCs. ? TCS at non-cytotoxic concentrations inhibits lipid formation in induced hMSCs. ? TCS decreases the expression of specific biomarkers of adipocyte differentiation. ? TCS at concentrations observed in human blood inhibits adipogenesis of hMSCs.

  13. Quantitative correlations among human mesenchymal stem cell mechanical properties and biological function

    E-Print Network [OSTI]

    Jolibois-Quinot, Remi

    2013-01-01T23:59:59.000Z

    Mesenchymal stem cells (MSCs) are derived from bone marrow, and are capable of proliferating and differentiating along multiple pathways such as osteoblasts, chondrocytes and adipocytes. MSCs offer the means for regenerative ...

  14. Nitric oxide activation of Keap1/Nrf2 signaling in human colon carcinoma cells

    E-Print Network [OSTI]

    Wogan, Gerald N.

    The transcription factor NF-E2-related nuclear factor 2 (Nrf2) regulates expression of genes that protect cells from oxidative damage. Here, we characterized nitric oxide (•NO)-induced Nrf2–Kelch-like ECH-associated protein ...

  15. Low Dose Radiation Response Curves, Networks and Pathways in Human Lymphoblastoid Cells Exposed from 1 to 10 cGy of Acute Gamma Radiation

    SciTech Connect (OSTI)

    Wyrobek, A. J.; Manohar, C. F.; Nelson, D. O.; Furtado, M. R.; Bhattacharya, M. S.; Marchetti, F.; Coleman, M.A.

    2011-04-18T23:59:59.000Z

    We investigated the low dose dependency of the transcriptional response of human cells to characterize the shape and biological functions associated with the dose response curve and to identify common and conserved functions of low dose expressed genes across cells and tissues. Human lymphoblastoid (HL) cells from two unrelated individuals were exposed to graded doses of radiation spanning the range of 1-10 cGy were analyzed by transcriptome profiling, qPCR and bioinformatics, in comparison to sham irradiated samples. A set of {approx}80 genes showed consistent responses in both cell lines; these genes were associated with homeostasis mechanisms (e.g., membrane signaling, molecule transport), subcellular locations (e.g., Golgi, and endoplasmic reticulum), and involved diverse signal transduction pathways. The majority of radiation-modulated genes had plateau-like responses across 1-10 cGy, some with suggestive evidence that transcription was modulated at doses below 1 cGy. MYC, FOS and TP53 were the major network nodes of the low-dose response in HL cells. Comparison our low dose expression findings in HL cells with those of prior studies in mouse brain after whole body exposure, in human keratinocyte cultures, and in endothelial cells cultures, indicates that certain components of the low dose radiation response are broadly conserved across cell types and tissues, independent of proliferation status.

  16. Confocal Microscopy for Modeling Electron Microbeam Irradiation of Skin

    SciTech Connect (OSTI)

    Miller, John H.; Chrisler, William B.; Wang, Xihai; Sowa, Marianne B.

    2011-08-01T23:59:59.000Z

    For radiation exposures employing targeted sources such as particle microbeams, the deposition of energy and dose will depend on the spatial heterogeneity of the spample. Although cell structural variations are relatively minor for two-dimensional cell cultures, they can vary significantly for fully differential tissues. Employing high-resolution confocal microscopy, we have determined the spatial distribution, size, and shape of epidermal kerantinocyte nuclei for the full-thickness EpiDerm skin model (MatTek, Ashland, VA). Application of these data to claculate the microdosimetry and microdistribution of energy deposition by an electron microbeam is discussed.

  17. Milk Fermented by Propionibacterium freudenreichii Induces Apoptosis of HGT-1 Human Gastric Cancer Cells

    E-Print Network [OSTI]

    Brest, Université de

    and/or as a food supplement to potentiate cancer therapeutic treatments. Citation: Cousin FJ, JouanMilk Fermented by Propionibacterium freudenreichii Induces Apoptosis of HGT-1 Human Gastric Cancer cancer is one of the most common cancers in the world. The ``economically developed countries'' life

  18. Stationary turbine component with laminated skin

    DOE Patents [OSTI]

    James, Allister W. (Orlando, FL)

    2012-08-14T23:59:59.000Z

    A stationary turbine engine component, such as a turbine vane, includes a internal spar and an external skin. The internal spar is made of a plurality of spar laminates, and the external skin is made of a plurality of skin laminates. The plurality of skin laminates interlockingly engage the plurality of spar laminates such that the external skin is located and held in place. This arrangement allows alternative high temperature materials to be used on turbine engine components in areas where their properties are needed without having to make the entire component out of such material. Thus, the manufacturing difficulties associated with making an entire component of such a material and the attendant high costs are avoided. The skin laminates can be made of advanced generation single crystal superalloys, intermetallics and refractory alloys.

  19. Regulation of human hepatocellular carcinoma cells by Spred2 and correlative studies on its mechanism

    SciTech Connect (OSTI)

    Ma, Xiao-Ni [Lanzhou University of Technology, Lanzhou 730050 (China)] [Lanzhou University of Technology, Lanzhou 730050 (China); Liu, Xiao-Yun [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China) [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Center for Disease Control and Prevention, Lanzhou Military Command, Lanzhou 730020 (China); Yang, Yue-Feng [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China)] [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Xiao, Feng-Jun [Lanzhou University of Technology, Lanzhou 730050 (China)] [Lanzhou University of Technology, Lanzhou 730050 (China); Li, Qing-Fang [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China)] [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Yan, Jun [Lanzhou University of Technology, Lanzhou 730050 (China)] [Lanzhou University of Technology, Lanzhou 730050 (China); Zhang, Qun-Wei; Wang, Li-Sheng [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China)] [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Li, Xue-Yan, E-mail: llglixueyan@163.com [Lanzhou University of Technology, Lanzhou 730050 (China)] [Lanzhou University of Technology, Lanzhou 730050 (China); Wang, Hua, E-mail: wanghua@bmi.ac.cn [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China)] [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China)

    2011-07-15T23:59:59.000Z

    Highlights: {yields} Hepatocellular carcinoma is inhibited by Spred2 through as yet unclear mechanisms. {yields} We studied the overexpression of Spred2 in cell line and murine tumor models of HCC. {yields} Spred2 inhibited cell proliferation and migration via attenuating ERK signaling. {yields} Spred2 overexpression induced apoptosis via caspase-3 and downregulated Mcl-1. {yields} A Spred2 knockdown markedly induced tumor growth in vivo. -- Abstract: Members of the Spred gene family are negative regulators of the Ras/Raf-1/ERK pathway, which has been associated with several features of the tumor malignancy. However, the effect of Spred genes on hepatocellular carcinoma (HCC) remains uninvestigated. In the present work, we analyzed the in vitro and in vivo effects of Spred2 expression on the hepatic carcinoma cell line, SMMC-7721. In addition to attenuated ERK activation, which inhibited the proliferation and migration of unstimulated and HGF-stimulated SMMC-7721 cells. Adenovirus-mediated Spred2 overexpression induced the activation of caspase-3 and apoptosis, as well as reduced the expression level of Mcl-1. Most importantly, the knockdown of Spred2 markedly enhanced tumor growth in vivo. In conclusion, these results suggest that Spred2 could qualify as a potential therapeutic target in HCC.

  20. Melatonin Protects Human Cells from Clustered DNA Damages, Killing and Acquisition of Soft Agar Growth Induced by X-rays or 970 MeV/n Fe ions

    SciTech Connect (OSTI)

    Das, B.; Sutherland, B.; Bennett, P. V.; Cutter, N. C.; Sutherland, J. C.

    2011-06-01T23:59:59.000Z

    We tested the ability of melatonin (N-acetyl-5 methoxytryptamine), a highly effective radical scavenger and human hormone, to protect DNA in solution and in human cells against induction of complex DNA clusters and biological damage induced by low or high linear energy transfer radiation (100 kVp X-rays, 970 MeV/nucleon Fe ions). Plasmid DNA in solution was treated with increasing concentrations of melatonin (0.0-3.5 mM) and were irradiated with X-rays. Human cells (28SC monocytes) were also irradiated with X-rays and Fe ions with and without 2 mM melatonin. Agarose plugs containing genomic DNA were subjected to Contour Clamped Homogeneous Electrophoretic Field (CHEF) followed by imaging and clustered DNA damages were measured by using Number Average length analysis. Transformation experiments on human primary fibroblast cells using soft agar colony assay were carried out which were irradiated with Fe ions with or without 2 mM melatonin. In plasmid DNA in solution, melatonin reduced the induction of single- and double-strand breaks. Pretreatment of human 28SC cells for 24 h before irradiation with 2 mM melatonin reduced the level of X-ray induced double-strand breaks by {approx}50%, of abasic clustered damages about 40%, and of Fe ion-induced double-strand breaks (41% reduction) and abasic clusters (34% reduction). It decreased transformation to soft agar growth of human primary cells by a factor of 10, but reduced killing by Fe ions only by 20-40%. Melatonin's effective reduction of radiation-induced critical DNA damages, cell killing, and striking decrease of transformation suggest that it is an excellent candidate as a countermeasure against radiation exposure, including radiation exposure to astronaut crews in space travel.

  1. Cell Stem Cell Clinical Progress

    E-Print Network [OSTI]

    Zandstra, Peter W.

    Cell Stem Cell Clinical Progress Rapid Expansion of Human Hematopoietic Stem Cells by Automated of Toronto, Toronto, ON M5G 1L7, Canada 6McEwen Centre for Regenerative Medicine, University Health Network

  2. Expression and proliferation profiles of PKC, JNK and p38MAPK in physiologically stretched human bladder smooth muscle cells

    SciTech Connect (OSTI)

    Wazir, Romel; Luo, De-Yi; Dai, Yi; Yue, Xuan; Tian, Ye; Wang, Kun-Jie, E-mail: kunjiewangatscu@163.com

    2013-08-30T23:59:59.000Z

    Highlights: •Stretch induces proliferation in human bladder smooth muscle cells (HBSMC). •5% Equibiaxial elongation produces maximum proliferation. •Physiologic stretch decreases apoptotic cell death. •PKC is involved in functional modulation of bladder. •JNK and p38 are not involved in proliferating HBSMC. -- Abstract: Objective: To determine protein kinase C (PKC), c-Jun NH2-Terminal Kinase (JNK) and P38 mitogen-activated protein kinases (p38MAPK) expression levels and effects of their respective inhibitors on proliferation of human bladder smooth muscle cells (HBSMCs) when physiologically stretched in vitro. Materials and methods: HBSMCs were grown on silicone membrane and stretch was applied under varying conditions; (equibiaxial elongation: 2.5%, 5%, 10%, 15%, 20%, 25%), (frequency: 0.05, 0.1, 0.2, 0.5, 1 Hz). Optimal physiological stretch was established by assessing proliferation with 5-Bromo-2-deoxyuridine (BrdU) assay and flow cytometry. PKC, JNK and p38 expression levels were analyzed by Western blot. Specificity was maintained by employing specific inhibitors; (GF109203X for PKC, SP600125 for JNK and SB203580 for p38MAPK), in some experiments. Results: Optimum proliferation was observed at 5% equibiaxial stretch (BrdU: 0.837 ± 0.026 (control) to 1.462 ± 0.023)%, (P < 0.05) and apoptotic cell death rate decreased from 16.4 ± 0.21% (control) to 4.5 ± 0.13% (P < 0.05) applied at 0.1 Hz. Expression of PKC was upregulated with slight increase in JNK and no change in p38MAPK after application of stretch. Inhibition had effects on proliferation (1.075 ± 0.024, P < 0.05 GF109203X); (1.418 ± 0.021, P > 0.05 SP600125) and (1.461 ± 0.01, P > 0.05 SB203580). These findings show that mechanical stretch can promote magnitude-dependent proliferative modulation through PKC and possibly JNK but not via p38MAPK in hBSMCs.

  3. Macrophage-stimulating protein attenuates gentamicin-induced inflammation and apoptosis in human renal proximal tubular epithelial cells

    SciTech Connect (OSTI)

    Lee, Ko Eun [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)] [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Eun Young [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)] [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Chang Seong; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)] [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Kyung Keun [Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)] [Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Lee, Jong Un [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)] [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Soo Wan, E-mail: skimw@chonnam.ac.kr [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)

    2013-05-10T23:59:59.000Z

    Highlights: •MSP/RON system is activated in rat kidney damaged by gentamicin. •MSP inhibits GM-induced cellular apoptosis and inflammation in HK-2 cells. •MSP attenuates GM-induced activation of MAPKs and NF-?B pathways in HK-2 cells. -- Abstract: The present study aimed to investigate whether macrophage-stimulating protein (MSP) treatment attenuates renal apoptosis and inflammation in gentamicin (GM)-induced tubule injury and its underlying molecular mechanisms. To examine changes in MSP and its receptor, recepteur d’origine nantais (RON) in GM-induced nephropathy, rats were injected with GM for 7 days. Human renal proximal tubular epithelial (HK-2) cells were incubated with GM for 24 h in the presence of different concentrations of MSP and cell viability was measured by MTT assay. Apoptosis was determined by flow cytometry of cells stained with fluorescein isothiocyanate-conjugated annexin V protein and propidium iodide. Expression of Bcl-2, Bax, caspase-3, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-?B), I?B-?, and mitogen-activated protein kinases (MAPKs) was analyzed by semiquantitative immunoblotting. MSP and RON expression was significantly greater in GM-treated rats, than in untreated controls. GM-treatment reduced HK-2 cell viability, an effect that was counteracted by MSP. Flow cytometry and DAPI staining revealed GM-induced apoptosis was prevented by MSP. GM reduced expression of anti-apoptotic protein Bcl-2 and induced expression of Bax and cleaved caspase 3; these effects and GM-induced expression of COX-2 and iNOS were also attenuated by MSP. GM caused MSP-reversible induction of phospho-ERK, phospho-JNK, and phospho-p38. GM induced NF-?B activation and degradation of I?B-?; the increase in nuclear NF-?B was blocked by inhibitors of ERK, JNK, p-38, or MSP pretreatment. These findings suggest that MSP attenuates GM-induced inflammation and apoptosis by inhibition of the MAPKs/NF-?B signaling pathways.

  4. Correlation and comparison of Nb/sub 2/ lymphoma cell bioassay with radioimmunoassay for human prolactin

    SciTech Connect (OSTI)

    Subramanian, M.G.; Spirtos, N.J.; Moghissi, K.S.; Magyar, D.M.; Hayes, M.F.; Gala, R.R.

    1984-12-01T23:59:59.000Z

    Serum samples from groups of men and women with normal and elevated prolactin (PRL) levels were assayed by radioimmunoassay (RIA) and by Nb/sub 2/ lymphoma cell bioassay (BA) for the presence of PRL. Because the Nb/sub 2/ lymphoma cells respond to both PRL and growth hormone, BA for PRL activity was carried out before and after neutralization of growth hormone in the serum samples. There were excellent correlations between RIA and BA both in euprolactinemic and hyperprolactinemic subjects. On an absolute basis, RIA and BA values were similar in the euprolactinemic group (6.6 +/- 0.8 versus 6.2 +/- 1.0), whereas in the hyperprolactinemic group, RIA values were significantly higher than the BA results. The two assay systems also appeared to correlate better in women who were hyperprolactinemic, with obvious menstrual cycle disturbances, than in hyperprolactinemic women without menstrual cycle disturbances.

  5. Biomolecular interactions and responses of human epithelial and macrophage cells to engineered nanomaterials.

    SciTech Connect (OSTI)

    Kotula, Paul Gabriel; Brozik, Susan Marie; Achyuthan, Komandoor E.; Greene, Adrienne Celeste; Timlin, Jerilyn Ann; Bachand, George David; Bachand, Marlene; Aaron, Jesse S.; Allen, Amy; Seagrave, Jean-Clare

    2011-12-01T23:59:59.000Z

    Engineered nanomaterials (ENMs) are increasingly being used in commercial products, particularly in the biomedical, cosmetic, and clothing industries. For example, pants and shirts are routinely manufactured with silver nanoparticles to render them 'wrinkle-free.' Despite the growing applications, the associated environmental health and safety (EHS) impacts are completely unknown. The significance of this problem became pervasive within the general public when Prince Charles authored an article in 2004 warning of the potential social, ethical, health, and environmental issues connected to nanotechnology. The EHS concerns, however, continued to receive relatively little consideration from federal agencies as compared with large investments in basic nanoscience R&D. The mounting literature regarding the toxicology of ENMs (e.g., the ability of inhaled nanoparticles to cross the blood-brain barrier; Kwon et al., 2008, J. Occup. Health 50, 1) has spurred a recent realization within the NNI and other federal agencies that the EHS impacts related to nanotechnology must be addressed now. In our study we proposed to address critical aspects of this problem by developing primary correlations between nanoparticle properties and their effects on cell health and toxicity. A critical challenge embodied within this problem arises from the ability to synthesize nanoparticles with a wide array of physical properties (e.g., size, shape, composition, surface chemistry, etc.), which in turn creates an immense, multidimensional problem in assessing toxicological effects. In this work we first investigated varying sizes of quantum dots (Qdots) and their ability to cross cell membranes based on their aspect ratio utilizing hyperspectral confocal fluorescence microscopy. We then studied toxicity of epithelial cell lines that were exposed to different sized gold and silver nanoparticles using advanced imaging techniques, biochemical analyses, and optical and mass spectrometry methods. Finally we evaluated a new assay to measure transglutaminase (TG) activity; a potential marker for cell toxicity.

  6. SENSITIZATION OF HUMAN OSTEOSARCOMA CELL LINE 143B WITH CALCITRIOL FOR CISPLATIN THERAPY

    E-Print Network [OSTI]

    Bhamidi Lakshmi, Surya Kameshwari Priyanka

    2012-08-31T23:59:59.000Z

    associated with OS are environmental such as exposure to radiation and beryllium oxide (2); epidemiological including associations with diseases such as retinoblastoma, Bloom syndrome and genetic impairments such as defects in cell cycle regulation with Rb... in the figure 2 (13). In addition to the role in bone mineral homeostasis, vitamin D has other non- calcemic actions such as thyroid function (17), insulin secretion (18), modulation of lymphocyte function and immune function (19), cellular differentiation...

  7. Norathyriol Suppresses Skin Cancers Induced by Solar Ultraviolet Radiation by Targeting ERK Kinases

    SciTech Connect (OSTI)

    Li, Jixia; Malakhova, Margarita; Mottamal, Madhusoodanan; Reddy, Kanamata; Kurinov, Igor; Carper, Andria; Langfald, Alyssa; Oi, Naomi; Kim, Myoung Ok; Zhu, Feng; Sosa, Carlos P.; Zhou, Keyuan; Bode, Ann M.; Dong, Zigang (Cornell); (Guangdong); (UMM)

    2012-06-27T23:59:59.000Z

    Ultraviolet (UV) irradiation is the leading factor in the development of skin cancer, prompting great interest in chemopreventive agents for this disease. In this study, we report the discovery of norathyriol, a plant-derived chemopreventive compound identified through an in silico virtual screening of the Chinese Medicine Library. Norathyriol is a metabolite of mangiferin found in mango, Hypericum elegans, and Tripterospermum lanceolatum and is known to have anticancer activity. Mechanistic investigations determined that norathyriol acted as an inhibitor of extracellular signal-regulated kinase (ERK)1/2 activity to attenuate UVB-induced phosphorylation in mitogen-activated protein kinases signaling cascades. We confirmed the direct and specific binding of norathyriol with ERK2 through a cocrystal structural analysis. The xanthone moiety in norathyriol acted as an adenine mimetic to anchor the compound by hydrogen bonds to the hinge region of the protein ATP-binding site on ERK2. Norathyriol inhibited in vitro cell growth in mouse skin epidermal JB6 P+ cells at the level of G{sub 2}-M phase arrest. In mouse skin tumorigenesis assays, norathyriol significantly suppressed solar UV-induced skin carcinogenesis. Further analysis indicated that norathyriol mediates its chemopreventive activity by inhibiting the ERK-dependent activity of transcriptional factors AP-1 and NF-{kappa}B during UV-induced skin carcinogenesis. Taken together, our results identify norathyriol as a safe new chemopreventive agent that is highly effective against development of UV-induced skin cancer.

  8. Neurotensin-induced Erk1/2 phosphorylation and growth of human colonic cancer cells are independent from growth factors receptors activation

    SciTech Connect (OSTI)

    Massa, Fabienne; Tormo, Aurelie; Beraud-Dufour, Sophie; Coppola, Thierry [Institut de Pharmacologie Moleculaire et Cellulaire, Universite de Nice-Sophia Antipolis, CNRS UMR 6097, 660 route des Lucioles, 06560 Valbonne (France)] [Institut de Pharmacologie Moleculaire et Cellulaire, Universite de Nice-Sophia Antipolis, CNRS UMR 6097, 660 route des Lucioles, 06560 Valbonne (France); Mazella, Jean, E-mail: mazella@ipmc.cnrs.fr [Institut de Pharmacologie Moleculaire et Cellulaire, Universite de Nice-Sophia Antipolis, CNRS UMR 6097, 660 route des Lucioles, 06560 Valbonne (France)] [Institut de Pharmacologie Moleculaire et Cellulaire, Universite de Nice-Sophia Antipolis, CNRS UMR 6097, 660 route des Lucioles, 06560 Valbonne (France)

    2011-10-14T23:59:59.000Z

    Highlights: {yields} We compare intracellular pathways of NT and EGF in HT29 cells. {yields} NT does not transactivate EGFR. {yields} Transactivation of EGFR is not a general rule in cancer cell growth. -- Abstract: Neurotensin (NT) promotes the proliferation of human colonic cancer cells by undefined mechanisms. We already demonstrated that, in the human colon adenocarcinoma cell line HT29, the effects of NT were mediated by a complex formed between the NT receptor-1 (NTSR1) and-3 (NTSR3). Here we examined cellular mechanisms that led to NT-induced MAP kinase phosphorylation and growth factors receptors transactivation in colonic cancer cells and proliferation in HT29 cells. With the aim to identify upstream signaling involved in NT-elicited MAP kinase activation, we found that the stimulatory effects of the peptide were totally independent from the activation of the epidermal growth factor receptor (EGFR) both in the HT29 and the HCT116 cells. NT was unable to promote phosphorylation of EGFR and to compete with EGF for its binding to the receptor. Pharmacological approaches allowed us to differentiate EGF and NT signaling in HT29 cells since only NT activation of Erk1/2 was shown to be sensitive to PKC inhibitors and since only NT increased the intracellular level of calcium. We also observed that NT was not able to transactivate Insulin-like growth factor receptor. Our findings indicate that, in the HT29 and HCT116 cell lines, NT stimulates MAP kinase phosphorylation and cell growth by a pathway which does not involve EGF system but rather NT receptors which transduce their own intracellular effectors. These results indicate that depending on the cell line used, blocking EGFR is not the general rule to inhibit NT-induced cancer cell proliferation.

  9. Overexpression of the human BCL-2 gene product results in growth enhancement of Epstein-Barr virus-immortalized B cells

    SciTech Connect (OSTI)

    Tsujimoto, Yoshihide (Wistar Institute of Anatomy and Biology, Philadelphia, PA (USA))

    1989-03-01T23:59:59.000Z

    The biological activity of the human BCL-2 gene product was analyzed in an Epstein-Barr virus (EBV)-infected human lymphoblastoid B-cell line transfected with BCL-2 sequences driven by the simian virus 40 promoter and enhancer. Overproduction of the BCL-2 protein conferred a selective growth advantage to the EBV-infected B cells as compared with control transfectants in low-serum medium and also after seeding at limiting dilution but did not render the cells tumorigenic in athymic nude mice. This growth enhancement was also seen in cells transfected with the BCL-2 gene with its own promoter juxtaposed to the immunoglobulin heavy chain gene enhancer, which represents the translocated form of the BCL-2 gene observed in follicular lymphomas with the t(14;18) translocation. The growth advantage of EBV-infected B cells overproducing the BCL-2 protein is neither due to the enhanced growth factor production nor due to an enhanced sensitivity of the BCL-2 transfectants to interleukins 1 or 6, although both lymphokines are known to stimulate proliferation of EBV-infected B-cell lines. The growth advantage of EBV-infected B-cell lines. The growth advantage of EBV-infected B cells by overproduction of the BCL-2 protein suggests the direct involvement of the BCL-2 gene product in the pathogenesis of follicular lymphoma.

  10. FGF signaling via MAPK is required early and improves Activin A-induced definitive endoderm formation from human embryonic stem cells

    SciTech Connect (OSTI)

    Sui, Lina, E-mail: linasui@vub.ac.be [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium)] [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Mfopou, Josue K. [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium)] [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Geens, Mieke; Sermon, Karen [Department of Embryology and Genetics, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium)] [Department of Embryology and Genetics, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Bouwens, Luc [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium)] [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium)

    2012-09-28T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer Deep study the FGF signaling role during DE specification in the context of hESCs. Black-Right-Pointing-Pointer DE differentiation from hESCs has an early dependence on FGF signaling. Black-Right-Pointing-Pointer A serum-free DE protocol is developed based on the findings. Black-Right-Pointing-Pointer The DE cells showed potential to differentiate into pancreatic progenitor cells. -- Abstract: Considering their unlimited proliferation and pluripotency properties, human embryonic stem cells (hESCs) constitute a promising resource applicable for cell replacement therapy. To facilitate this clinical translation, it is critical to study and understand the early stage of hESCs differentiation wherein germ layers are defined. In this study, we examined the role of FGF signaling in Activin A-induced definitive endoderm (DE) differentiation in the absence of supplemented animal serum. We found that activated FGF/MAPK signaling is required at the early time point of Activin A-induced DE formation. In addition, FGF activation increased the number of DE cells compared to Activin A alone. These DE cells could further differentiate into PDX1 and NKX6.1 positive pancreatic progenitors in vitro. We conclude that Activin A combined with FGF/MAPK signaling efficiently induce DE cells in the absence of serum. These findings improve our understanding of human endoderm formation, and constitute a step forward in the generation of clinical grade hESCs progenies for cell therapy.

  11. Hepatitis C virus E2 protein promotes human hepatoma cell proliferation through the MAPK/ERK signaling pathway via cellular receptors

    SciTech Connect (OSTI)

    Zhao Lanjuan [Department of Microbiology, Second Military Medical University, 800 Xiang-Yin Road, Shanghai 200433 (China); Wang Lu [Department of Microbiology, Second Military Medical University, 800 Xiang-Yin Road, Shanghai 200433 (China); Ren Hao [Department of Microbiology, Second Military Medical University, 800 Xiang-Yin Road, Shanghai 200433 (China); Cao Jie [Department of Microbiology, Second Military Medical University, 800 Xiang-Yin Road, Shanghai 200433 (China); Li Li [Department of Laboratory Diagnosis, Changzheng Hospital, Shanghai 200003 (China); Ke Jinshan [Department of Laboratory Diagnosis, Changzheng Hospital, Shanghai 200003 (China); Qi Zhongtian [Department of Microbiology, Second Military Medical University, 800 Xiang-Yin Road, Shanghai 200433 (China)]. E-mail: qizt53@hotmail.com

    2005-04-15T23:59:59.000Z

    Dysregulation of mitogen-activated protein kinase (MAPK) signaling pathways by various viruses has been shown to be responsible for viral pathogenicity. The molecular mechanism by which hepatitis C virus (HCV) infection caused human liver diseases has been investigated on the basis of abnormal intracellular signal events. Current data are very limited involved in transmembrane signal transduction triggered by HCV E2 protein. Here we explored regulation of the MAPK/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway by E2 expressed in Chinese hamster oval cells. In human hepatoma Huh-7 cells, E2 specifically activated the MAPK/ERK pathway including downstream transcription factor ATF-2 and greatly promoted cell proliferation. CD81 and low density lipoprotein receptor (LDLR) on the cell surface mediated binding of E2 to Huh-7 cells. The MAPK/ERK activation and cell proliferation driven by E2 were suppressed by blockage of CD81 as well as LDLR. Furthermore, pretreatment with an upstream kinase MEK1/2 inhibitor U0126 also impaired the MAPK/ERK activation and cell proliferation induced by E2. Our results suggest that the MAPK/ERK signaling pathway triggered by HCV E2 via its receptors maintains survival and growth of target cells.

  12. Dominant negative and loss of function mutations of the c-kit (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism

    SciTech Connect (OSTI)

    Spritz, R.A.; Giebel, L.B.; Holmes, S.A. (University of Wisconsin, Madison (United States))

    1992-02-01T23:59:59.000Z

    Piebaldism is an autosomal dominant disorder of melanocyte development and is characterized by congenital white parches of skin and hair from which melanocytes are completely absent. A similar disorder of the mouse, 'dominant white spotting' (W), results from mutations of the c-kit proto-oncogene, which encodes the cellular tyrosine kinases receptor for the mast/stem cell growth factor. The authors have identified c-kit gene mutations in three patients with piebaldism. A missense substitution (Phe[r arrow]Leu) at codon 584, within the tyrosine kinases domain, is associated with a severe piebald phenotype, whereas two different frameshifts, within codons 561 and 642, are both associated with a variable and relatively mild piebald phenotype. This is consistent with a possible 'dominant negative' effect of missense c-kit polypeptides on the function of the dimeric receptor.

  13. Reactive oxygen species mediates homocysteine-induced mitochondrial biogenesis in human endothelial cells: Modulation by antioxidants

    SciTech Connect (OSTI)

    Perez-de-Arce, Karen [Departamento de Nutricion, Diabetes y Metabolismo, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago (Chile); Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago (Chile); Foncea, Rocio [Departamento de Nutricion, Diabetes y Metabolismo, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago (Chile)]. E-mail: rfoncea@med.puc.cl; Leighton, Federico [Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago (Chile)

    2005-12-16T23:59:59.000Z

    It has been proposed that homocysteine (Hcy)-induces endothelial dysfunction and atherosclerosis by generation of reactive oxygen species (ROS). A previous report has shown that Hcy promotes mitochondrial damage. Considering that oxidative stress can affect mitochondrial biogenesis, we hypothesized that Hcy-induced ROS in endothelial cells may lead to increased mitochondrial biogenesis. We found that Hcy-induced ROS (1.85-fold), leading to a NF-{kappa}B activation and increase the formation of 3-nitrotyrosine. Furthermore, expression of the mitochondrial biogenesis factors, nuclear respiratory factor-1 and mitochondrial transcription factor A, was significantly elevated in Hcy-treated cells. These changes were accompanied by increase in mitochondrial mass and higher mRNA and protein expression of the subunit III of cytochrome c oxidase. These effects were significantly prevented by pretreatment with the antioxidants, catechin and trolox. Taken together, our results suggest that ROS is an important mediator of mitochondrial biogenesis induced by Hcy, and that modulation of oxidative stress by antioxidants may protect against the adverse vascular effects of Hcy.

  14. The TAL1 complex targets the FBXW7 tumor suppressor by activating miR-223 in human T cell acute lymphoblastic leukemia

    E-Print Network [OSTI]

    Mansour, Marc R.

    The oncogenic transcription factor TAL1/SCL is aberrantly expressed in 60% of cases of human T cell acute lymphoblastic leukemia (T-ALL) and initiates T-ALL in mouse models. By performing global microRNA (miRNA) expression ...

  15. The oncogenic action of ionizing radiation on rat skin

    SciTech Connect (OSTI)

    Burns, F.J.; Garte, S.J.

    1992-01-01T23:59:59.000Z

    The multistage theory of carcinogenesis specifies that cells progress to cancer through a series of discrete, irreversible genetic alterations, but data on radiation-induced cancer incidence in rat skin suggests that an intermediate repairable alteration may occur. Data are presented on cancer induction in rat skin exposed to an electron beam (LET=0.34 keV/[mu]), a neon ion beam (LET=45) or an argon ion beam (LET=125). The rats were observed for tumors at least 78 weeks with squamous and basal cell carcinomas observed. The total cancer yield was fitted by the quadratic equation, and the equation parameters were estimated by linear regression for each type of radiation. Analysis of the DNA from the electron-induced carcinomas indicated that K-ras and/or c-myc oncogenes were activated. In situ hybridization indicated that the cancers contain subpopulations of cells with differing amounts of c-myc and H-ras amplification. The results are consistent with the idea that ionizing radiation produces stable, carcinogenically relevant lesions via 2 repairable events at low LET and via a non-repairable linked event pathway at high LET; either pathway may advance the cell by 1 stage. The proliferative response of rat epidermis following exposure to ionizing radiation was quantified by injection of [sup 14]C-thymidine. The return of these cells to S-phase a second time was detected by a second label ([sup 3]H). When the labeled cells were in G1-phase, the dorsal skin was irradiated with X-rays. All labeling indices were determined. The [sup 14]C labeling index was constant and unaffected by the radiation. The proportion of all cells entering S-phase averaged 3.5% at 18 hr and increased after 44, 52 and 75 hr to average levels of 11.8%, 5. 3%, and 6.6% at 0, 10 and 25 Gy respectively. The proportion of S-phase cells labeled with [sup 14]C increased after 42 hr and remained relatively constant thereafter.

  16. NRF2 activation is involved in ozonated human serum upregulation of HO-1 in endothelial cells

    SciTech Connect (OSTI)

    Pecorelli, Alessandra [Department of Molecular and Developmental Medicine, University of Siena (Italy); Child Neuropsychiatry Unit, University Hospital, AOUS, Siena (Italy); Bocci, Velio [Department of Physiology, University of Siena (Italy); Acquaviva, Alessandra [Department of Molecular and Developmental Medicine, University of Siena (Italy); Belmonte, Giuseppe [Department of Biomedical Sciences, University of Siena (Italy); Gardi, Concetta [Department of Molecular and Developmental Medicine, University of Siena (Italy); Virgili, Fabio [INRAN, Rome (Italy); Ciccoli, Lucia [Department of Molecular and Developmental Medicine, University of Siena (Italy); Valacchi, Giuseppe, E-mail: giuseppe.valacchi@unife.it [Department of Life Sciences and Biotechnology, University of Ferrara (Italy); Department of Food and Nutrition, Kyung Hee University, Seoul (Korea, Republic of)

    2013-02-15T23:59:59.000Z

    During the last decade, it has been shown that the activation of NRF2 and the binding to electrophile-responsive element (EpREs), stimulates the expression of a great number of genes responsible for the synthesis of phase I and phase II proteins, including antioxidants enzymes and heme oxygenase-1 (HO-1). This critical cell response occurs in cardiovascular, degenerative and chronic infective diseases aggravated by a chronic oxidative stress. In our previous reports we have shown that ozonated plasma is able to up-regulate HO-1 expression in endothelial cells. In the present work we investigated a candidate mechanism involved in this process. After treatment with increasing doses of ozonated serum (20, 40 and 80 ?g/mL O{sub 3} per mL of serum), a clear dose dependent activation of NRF2 and the subsequent induction of HO-1 and NAD(P)H quinone oxidoreductase 1(NQO1) was observed. This effect was also present when cells were treated with serum and hydrogen peroxide (H{sub 2}O{sub 2}) or serum and 4-hydroxynonenal (4HNE). Moreover, the treatment with ozonated serum was associated with a dose-dependent activation of extracellular-signal-regulated kinases (ERK1/2) and p38 MAP kinases (p38), not directly involved in NRF2 activation. These data, provide a new insight on the mechanism responsible for the induction of HO-1 expression by ozonated serum in the endothelium, and have a practical importance as an expedient approach to the treatment of patients with both effective orthodox drugs and ozonated autohemotherapy, targeted to the restoration of redox homeostasis. - Highlights: ? Endothelial HO1 is upregulated by ozonated plasma ? This activation is induced by NRF2 and it is ERK independent. ? 4HNE and H{sub 2}O{sub 2} are the main molecules involved in this process. ? Ozonated plasma induced a hormetic effect ? Combination of orthodox medicine and ozonated plasma can be a useful treatment.

  17. Efficient elasticity for character skinning with contact and collisions Aleka McAdams1,3

    E-Print Network [OSTI]

    Liblit, Ben

    -level character skinning system. CR Categories: I.6.8 [Simulation and Modeling]: Types of Simulation--Animation aspect is the production of life-like deformations for soft tissues comprising both humans and animals Animation Studios 2 PDI/DreamWorks 3 University of California, Los Angeles 4 University of Wisconsin

  18. An Examination of the Effect of Decaying Exponential Pulse Electric Fields on Cell Mortality in Murine Spleenocytes, Hybridomas, and Human Natural Killer Cells

    E-Print Network [OSTI]

    Stryker, Gabrielle A.

    have also been used for production of monoclonal antibodies [6], cell-tissue fusion [3], and cell and the pellet was re- suspended at 3 x 105 cells/ml o

  19. autologous serum skin: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    and Information Sciences Websites Summary: specialized sub- classes, namely "bikini" "porn" and "skin" "non-skin", respectively. The extracted pornographic image classifiers....

  20. acute nontraumatic skin: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    and Information Sciences Websites Summary: specialized sub- classes, namely "bikini" "porn" and "skin" "non-skin", respectively. The extracted pornographic image classifiers....

  1. Detecting pornographic images by localizing skin Sotiris Karavarsamisa

    E-Print Network [OSTI]

    Blekas, Konstantinos

    specialized sub- classes, namely "bikini" / "porn" and "skin" / "non-skin", respectively. The extracted pornographic image classifiers. Index Terms convex hull calculation, multi-class classification, porn detection

  2. alter skin microcirculation: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    and Information Sciences Websites Summary: specialized sub- classes, namely "bikini" "porn" and "skin" "non-skin", respectively. The extracted pornographic image classifiers....

  3. ameliorate genetic skin: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    and Information Sciences Websites Summary: specialized sub- classes, namely "bikini" "porn" and "skin" "non-skin", respectively. The extracted pornographic image classifiers....

  4. Impaired NFAT and NF?B activation are involved in suppression of CD40 ligand expression by ?{sup 9}-tetrahydrocannabinol in human CD4{sup +} T cells

    SciTech Connect (OSTI)

    Ngaotepprutaram, Thitirat [Department of Pharmacology and Toxicology, Michigan State University (United States); Center for Integrative Toxicology, Michigan State University (United States); Kaplan, Barbara L.F. [Department of Pharmacology and Toxicology, Michigan State University (United States); Center for Integrative Toxicology, Michigan State University (United States); Neuroscience Program, Michigan State University (United States); Kaminski, Norbert E., E-mail: kamins11@msu.edu [Department of Pharmacology and Toxicology, Michigan State University (United States); Center for Integrative Toxicology, Michigan State University (United States)

    2013-11-15T23:59:59.000Z

    We have previously reported that ?{sup 9}-tetrahydrocannabinol (?{sup 9}-THC), the main psychoactive cannabinoid in marijuana, suppresses CD40 ligand (CD40L) expression by activated mouse CD4{sup +} T cells. CD40L is involved in pathogenesis of many autoimmune and inflammatory diseases. In the present study, we investigated the molecular mechanism of ?{sup 9}-THC-mediated suppression of CD40L expression using peripheral blood human T cells. Pretreatment with ?{sup 9}-THC attenuated CD40L expression in human CD4{sup +} T cells activated by anti-CD3/CD28 at both the protein and mRNA level, as determined by flow cytometry and quantitative real-time PCR, respectively. Electrophoretic mobility shift assays revealed that ?{sup 9}-THC suppressed the DNA-binding activity of both NFAT and NF?B to their respective response elements within the CD40L promoter. An assessment of the effect of ?{sup 9}-THC on proximal T cell-receptor (TCR) signaling induced by anti-CD3/CD28 showed significant impairment in the rise of intracellular calcium, but no significant effect on the phosphorylation of ZAP70, PLC?1/2, Akt, and GSK3?. Collectively, these findings identify perturbation of the calcium-NFAT and NF?B signaling cascade as a key mechanistic event by which ?{sup 9}-THC suppresses human T cell function. - Highlights: • ?{sup 9}-THC attenuated CD40L expression in activated human CD4+ T cells. • ?{sup 9}-THC suppressed DNA-binding activity of NFAT and NF?B. • ?{sup 9}-THC impaired elevation of intracellular Ca2+. • ?{sup 9}-THC did not affect phosphorylation of ZAP70, PLC?1/2, Akt, and GSK3?.

  5. Beyond the skin bag: on the moral responsibility of extended agencies

    E-Print Network [OSTI]

    Hanson, F. Allan

    2009-03-01T23:59:59.000Z

    and extended agency The view of the subject as only the human individual is known as methodological individualism. This theory holds that subjects are human beings entirely contained in their “skin bags” (Clark 2003), that maintain their identity... to ride a bicycle. “Be careful not to run into people or things, don’t crash your bike or hurt yourself, and especially don’t ride into the street without looking.” Her responsibility with the bicycle is, however, considerably less momentous than...

  6. Skin thickness effects on in vivo LXRF

    SciTech Connect (OSTI)

    Preiss, I.L.; Washington, W. II [Rensselaer Polytechnic Inst., Troy, NY (United States)

    1995-12-31T23:59:59.000Z

    The analysis of lead concentration in bone utilizing LXRF can be adversely effected by overlying issue. A quantitative measure of the attenuation of the 10.5 keV Pb L a x-ray signal by skin and skin equivalent plastic has been conducted. Concentration ranges in plaster of Paris and goat bone from 7 to 90 ppm with attenuators of Lucite{reg_sign} and pig skin were examined. It is concluded that no quantitative or semi quantitative analysis can be achieved if overlying sue thickness exceeds 3 mm for Ph concentrations of less than 30 porn Ph in bone.

  7. Skin friction for steel piles in sand

    E-Print Network [OSTI]

    Sulaiman, Ibrahim Hikmat

    1967-01-01T23:59:59.000Z

    MOVEMENT 4) For dry pile tests at initial void ratio of 0. 63, the assumption of a Coulomb type failure applies and the envelope is shown in Figure 23. The skin friction computed is the total friction caused by applied load. and. the static load caused... Sand 43 22. Skin Friction-Chamber Pressure Ratio Versus Pile Movement for Dense Dry Sand 44 23 ~ 24. Mohr Envelope for Skin Friction Measured. and Assumed. Pile Deformation 49 25 ~ Computed and Actual Load-Movement Curves for Test Pile 1 26...

  8. Proc. 3rd International Conference on Networked Sensing Systems (INSS 2006), pp. 55-60, Rosemont, Illinois (USA), May, 2006. A Whole Body Artificial Skin

    E-Print Network [OSTI]

    Shinoda, Hiroyuki

    are required to be more cautious about surrounding environments than robots in industrial factories because a tactile sensor skin as one of applications of the system. In this application, the cells are not only within its sensing area. The resulting robot skin is soft, stretchable, and able to cover a large area

  9. Short-hairpin RNA-mediated Heat shock protein 90 gene silencing inhibits human breast cancer cell growth in vitro and in vivo

    SciTech Connect (OSTI)

    Zuo, Keqiang [Department of General Surgery, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072 (China)] [Department of General Surgery, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072 (China); Li, Dan [Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072 (China)] [Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072 (China); Pulli, Benjamin [Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, MA 02114 (United States)] [Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, MA 02114 (United States); Yu, Fei; Cai, Haidong; Yuan, Xueyu [Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072 (China)] [Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072 (China); Zhang, Xiaoping, E-mail: zxpsibs@163.com [Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072 (China)] [Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072 (China); Lv, Zhongwei, E-mail: heyixue163@163.com [Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072 (China)] [Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072 (China)

    2012-05-04T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer Hsp90 is over-expressed in human breast cancer. Black-Right-Pointing-Pointer The shRNA-mediated gene silencing of Hsp90 resulted in inhibition of cell growth. Black-Right-Pointing-Pointer Akt and NF-kB were down-regulation after transfection due to Hsp90 silencing. Black-Right-Pointing-Pointer The tumor growth ratio was decline due to Hsp90 silencing. Black-Right-Pointing-Pointer The PCNA expression was down-regulation due to Hsp90 silencing. -- Abstract: Hsp90 interacts with proteins that mediate signaling pathways involved in the regulation of essential processes such as proliferation, cell cycle control, angiogenesis and apoptosis. Hsp90 inhibition is therefore an attractive strategy for blocking abnormal pathways that are crucial for cancer cell growth. In the present study, the role of Hsp90 in human breast cancer MCF-7 cells was examined by stably silencing Hsp90 gene expression with an Hsp90-silencing vector (Hsp90-shRNA). RT-PCR and Western blot analyses showed that Hsp90-shRNA specifically and markedly down-regulated Hsp90 mRNA and protein expression. NF-kB and Akt protein levels were down-regulated in Hsp90-shRNA transfected cells, indicating that Hsp90 knockout caused a reduction of survival factors and induced apoptosis. Treatment with Hsp90-shRNA significantly increased apoptotic cell death and caused cell cycle arrest in the G1/S phase in MCF-7 cells, as shown by flow cytometry. Silencing of Hsp90 also reduced cell viability, as determined by MTT assay. In vivo experiments showed that MCF-7 cells stably transfected with Hsp90-shRNA grew slowly in nude mice as compared with control groups. In summary, the Hsp90-shRNA specifically silenced the Hsp90 gene, and inhibited MCF-7 cell growth in vitro and in vivo. Possible molecular mechanisms underlying the effects of Hsp90-shRNA include the degradation of Hsp90 breast cancer-related client proteins, the inhibition of survival signals and the upregulation of apoptotic pathways. shRNA-mediated interference may have potential therapeutic utility in human breast cancer.

  10. Pancreatic beta cell failure in obese mice with human-like CMP-Neu5Ac hydroxylase deficiency

    E-Print Network [OSTI]

    Kavaler, Sarah

    2011-01-01T23:59:59.000Z

    Igf-1 receptor-mediated beta-cell development and peripheralGerich, J. (1995) Pancreatic beta-cell dysfunction as theC. , and Bodkin, N. L. (1990) Beta-cell hyperresponsiveness:

  11. Interleukin-6 triggers human cerebral endothelial cells proliferation and migration: The role for KDR and MMP-9

    SciTech Connect (OSTI)

    Yao, Jianhua S. [Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94110 (United States); Zhai Wenwu [Department of Lung Biology, University of California, San Francisco, CA 94110 (United States); Young, William L. [Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94110 (United States); Department of Neurological Surgery, University of California, San Francisco, CA 94110 (United States); Department of Neurology, University of California, San Francisco, CA 94110 (United States); Yang Guoyuan [Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94110 (United States) and Department of Neurological Surgery, University of California, San Francisco, CA 94110 (United States)]. E-mail: gyyang@anesthesia.ucsf.edu

    2006-04-21T23:59:59.000Z

    Interleukin-6 (IL-6) is involved in angiogenesis. However, the underlying mechanisms are unknown. Using human cerebral endothelial cell (HCEC), we report for First time that IL-6 triggers HCEC proliferation and migration in a dose-dependent manner, specifically associated with enhancement of VEGF expression, up-regulated and phosphorylated VEGF receptor-2 (KDR), and stimulated MMP-9 secretion. We investigated the signal pathway of IL-6/IL-6R responsible for KDR's regulation. Pharmacological inhibitor of PI3K failed to inhibit IL-6-mediated VEGF overexpression, while blocking ERK1/2 with PD98059 could abolish IL-6-induced KDR overexpression. Further, neutralizing endogenous VEGF attenuated KDR expression and phosphorylation, suggesting that IL-6-induced KDR activation is independent of VEGF stimulation. MMP-9 inhibitor GM6001 significantly decreases HCEC proliferation and migration (p < 0.05), indicating the crucial function of MMP-9 in promoting angiogenic changes in HCECs. We conclude that IL-6 triggers VEGF-induced angiogenic activity through increasing VEGF release, up-regulates KDR expression and phosphorylation through activating ERK1/2 signaling, and stimulates MMP-9 overexpression.

  12. Hypoxia reduces constitutive and TNF-{alpha}-induced expression of monocyte chemoattractant protein-1 in human proximal renal tubular cells

    SciTech Connect (OSTI)

    Li Xuan [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Kimura, Hideki [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan)]. E-mail: hkimura@fmsrsa.fukui-med.ac.jp; Hirota, Kiichi [Department of Anesthesia, Tazuke Kofukai Medical Research Institute Kitano Hospital, Osaka (Japan); Department of Anesthesia, School of Medicine, Kyoto University, Kyoto (Japan); Sugimoto, Hidehiro [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Yoshida, Haruyoshi [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan)

    2005-10-07T23:59:59.000Z

    Chronic hypoxia has been reported to be associated with macrophage infiltration in progressive forms of kidney disease. Here, we investigated the regulatory effects of hypoxia on constitutive and TNF-{alpha}-stimulated expression of monocyte chemoattractant protein-1 (MCP-1) in cultured human proximal renal tubular cells (HPTECs). Hypoxia reduced constitutive MCP-1 expression at the mRNA and protein levels in a time-dependent fashion for up to 48 h. Hypoxia also inhibited MCP-1 up-regulation by TNF-{alpha}. Treatment with actinomycin D showed that hypoxic down-regulation of MCP-1 expression resulted mainly from a decrease in the transcription but not the mRNA stability. Immunoblot and immunofluorescence analyses revealed that treatment with hypoxia or an iron chelator, desferrioxamine, induced nuclear accumulation of hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) in HPTECs. Desferrioxamine mimicked hypoxia in the reduction of MCP-1 expression. However, overexpression of a dominant negative form of HIF-1{alpha} did not abolish the hypoxia-induced reduction of MCP-1 expression in HPTECs. These results suggest that hypoxia is an important negative regulator of monocyte chemotaxis to the renal inflamed interstitium, by reducing MCP-1 expression partly via hypoxia-activated signals other than the HIF-1 pathway.

  13. Heritable Genetic Changes in Cells Recovered From Irradiated 3D Tissue Constructs

    SciTech Connect (OSTI)

    Michael Cornforth

    2012-03-26T23:59:59.000Z

    Combining contemporary cytogenetic methods with DNA CGH microarray technology and chromosome flow-sorting increases substantially the ability to resolve exchange breakpoints associated with interstitial deletions and translocations, allowing the consequences of radiation damage to be directly measured at low doses, while also providing valuable insights into molecular mechanisms of misrepair processes that, in turn, identify appropriate biophysical models of risk at low doses. Specific aims apply to cells recovered from 3D tissue constructs of human skin and, for the purpose of comparison, the same cells irradiated in traditional 2D cultures. The project includes research complementary to NASA/HRP space radiation project.

  14. Metabolomic Response of Human Skin Tissue to Low Dose Ionizing...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    for IR exposure at low doses can help provide a scientific basis for establishing radiation protection standards. Little is known regarding the physiological responses to...

  15. Assignment of the human RT6 gene to 11q13 by PCR screening of somatic cell hybrids and in situ hybridization

    SciTech Connect (OSTI)

    Koch-Nolte, F.; Haag, F.; Kuehl, M.; Thiele, H.G.; Singh, S. (Univ. Hospital, Hamburg (Germany)); Van Heyningen, V. (Medical Research Council, Edinburgh (United Kingdom)); Hoovers, J. (Univ. of Amsterdam (Netherlands)); Grzeschik, K.H. (Univ. of Marburg (Germany))

    1993-11-01T23:59:59.000Z

    RT6 is a T cell membrane protein that has attracted interest because a defect in RT6 expression is associated with susceptibility to autoimmune type I diabetes in DP-BB rats and NOD mice. Using PCR screening of human/rodent somatic cell hybrids and fluorescence in situ hybridization, the authors have determined that the gene for the human RT6 homologue is located at 11q13, centromeric to the gene for tyrosinase (TYR, albino locus) and telomeric to that for fibroblast growth factor 4 (FGF4). The data suggest that the human RT6 gene constitutes a new linkage group with TYR and the gene for olfactory marker protein (OMP) on 11q, which has a counterpart in mouse chromosome 7. Thus, in the human, the RT6 locus is dissociated from the hemoglobin [beta] chain locus (HBB) and its neighboring conserved linkage group at 11q15, in contrast to the mouse, in which RT6 shows a tighter linkage to Hbb than to Tyr. The results support the conclusion that there has been considerable intrachromosomal reshuffling of linked genes since the divergence of primates and rodents. 9 refs., 1 fig.

  16. Studying the protein expression in human B lymphoblastoid cells exposed to 1.8-GHz (GSM) radiofrequency radiation (RFR) with protein microarray

    SciTech Connect (OSTI)

    Zhijian, Chen [Department of Environmental and Occupational Health, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, Zhejiang (China) [Department of Environmental and Occupational Health, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, Zhejiang (China); Institute of Environmental Health, Medical College, Zhejiang University, Hangzhou 310058, Zhejiang (China); Xiaoxue, Li [Institute of Environmental Health, Medical College, Zhejiang University, Hangzhou 310058, Zhejiang (China)] [Institute of Environmental Health, Medical College, Zhejiang University, Hangzhou 310058, Zhejiang (China); Wei, Zheng [Zhejiang International Travel Healthcare Center, 230 Zhonghezhong Road, Hangzhou 310003 (China)] [Zhejiang International Travel Healthcare Center, 230 Zhonghezhong Road, Hangzhou 310003 (China); Yezhen, Lu; Jianlin, Lou; Deqiang, Lu; Shijie, Chen; Lifen, Jin [Institute of Environmental Health, Medical College, Zhejiang University, Hangzhou 310058, Zhejiang (China)] [Institute of Environmental Health, Medical College, Zhejiang University, Hangzhou 310058, Zhejiang (China); Jiliang, He, E-mail: he_jiliang@hotmail.com [Institute of Environmental Health, Medical College, Zhejiang University, Hangzhou 310058, Zhejiang (China)] [Institute of Environmental Health, Medical College, Zhejiang University, Hangzhou 310058, Zhejiang (China)

    2013-03-29T23:59:59.000Z

    Highlights: ? Protein microarray shows the differential expression of 27 proteins induced by RFR. ? RPA32 related to DNA repair is down-regulated in Western blot. ? p73 related to cell genome stability and apoptosis is up-regulated in Western blot. -- Abstract: In the present study, the protein microarray was used to investigate the protein expression in human B-cell lymphoblastoid cells intermittently exposed to 1.8-GHz GSM radiofrequency radiation (RFR) at the specific absorption rate (SAR) of 2.0 W/kg for 24 h. The differential expression of 27 proteins was found, which were related to DNA damage repair, apoptosis, oncogenesis, cell cycle and proliferation (ratio >1.5-fold, P < 0.05). The results validated with Western blot assay indicated that the expression of RPA32 was significantly down-regulated (P < 0.05) while the expression of p73 was significantly up-regulated in RFR exposure group (P < 0.05). Because of the crucial roles of those proteins in DNA repair and cell apoptosis, the results of present investigation may explain the biological effects of RFR on DNA damage/repair and cell apoptosis.

  17. Elevated extracellular calcium increases expression of bone morphogenetic protein-2 gene via a calcium channel and ERK pathway in human dental pulp cells

    SciTech Connect (OSTI)

    Tada, Hiroyuki [Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan)] [Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan); Nemoto, Eiji, E-mail: e-nemoto@umin.ac.jp [Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan)] [Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan); Kanaya, Sousuke; Hamaji, Nozomu; Sato, Hisae; Shimauchi, Hidetoshi [Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan)] [Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan)

    2010-04-16T23:59:59.000Z

    Dental pulp cells, which have been shown to share phenotypical features with osteoblasts, are capable of differentiating into odontoblast-like cells and generating a dentin-like mineral structure. Elevated extracellular Ca{sup 2+}Ca{sub o}{sup 2+} has been implicated in osteogenesis by stimulating the proliferation and differentiation of osteoblasts; however, the role of Ca{sub o}{sup 2+} signaling in odontogenesis remains unclear. We found that elevated Ca{sub o}{sup 2+} increases bone morphogenetic protein (BMP)-2 gene expression in human dental pulp cells. The increase was modulated not only at a transcriptional level but also at a post-transcriptional level, because treatment with Ca{sup 2+} increased the stability of BMP-2 mRNA in the presence of actinomycin D, an inhibitor of transcription. A similar increase in BMP-2 mRNA level was observed in other human mesenchymal cells from oral tissue; periodontal ligament cells and gingival fibroblasts. However, the latter cells exhibited considerably lower expression of BMP-2 mRNA compared with dental pulp cells and periodontal ligament cells. The BMP-2 increase was markedly inhibited by pretreatment with an extracellular signal-regulated kinase (ERK) inhibitor, PD98059, and partially inhibited by the L-type Ca{sup 2+} channels inhibitor, nifedipine. However, pretreatment with nifedipine had no effect on ERK1/2 phosphorylation triggered by Ca{sup 2+}, suggesting that the Ca{sup 2+} influx from Ca{sup 2+} channels may operate independently of ERK signaling. Dental pulp cells do not express the transcript of Ca{sup 2+}-sensing receptors (CaSR) and only respond slightly to other cations such as Sr{sup 2+} and spermine, suggesting that dental pulp cells respond to Ca{sub o}{sup 2+} to increase BMP-2 mRNA expression in a manner different from CaSR and rather specific for Ca{sub o}{sup 2+} among cations.

  18. MiR-145 is downregulated in human ovarian cancer and modulates cell growth and invasion by targeting p70S6K1 and MUC1

    SciTech Connect (OSTI)

    Wu, Huijuan [Department of Gynecological Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060 (China)] [Department of Gynecological Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060 (China); Xiao, ZhengHua [Department of gynecology, Yongchuan Affiliated Hospital of Chongqing Medical University, Chongqing City 404100 (China)] [Department of gynecology, Yongchuan Affiliated Hospital of Chongqing Medical University, Chongqing City 404100 (China); Wang, Ke; Liu, Wenxin [Department of Gynecological Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060 (China)] [Department of Gynecological Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060 (China); Hao, Quan, E-mail: quanhao2002@163.com [Department of Gynecological Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060 (China)] [Department of Gynecological Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060 (China)

    2013-11-29T23:59:59.000Z

    Highlights: •MiR-145 is downregulated in human ovarian cancer. •MiR-145 targets p70S6K1 and MUC1. •p70S6K1 and MUC1 are involved in miR-145 mediated tumor cell growth and cell invasion, respectively. -- Abstract: MicroRNAs (miRNAs) are a family of small non-coding RNA molecules that regulate gene expression at post-transcriptional levels. Previous studies have shown that miR-145 is downregulated in human ovarian cancer; however, the roles of miR-145 in ovarian cancer growth and invasion have not been fully demonstrated. In the present study, Northern blot and qRT-PCR analysis indicate that miR-145 is downregulated in ovarian cancer tissues and cell lines, as well as in serum samples of ovarian cancer, compared to healthy ovarian tissues, cell lines and serum samples. Functional studies suggest that miR-145 overexpression leads to the inhibition of colony formation, cell proliferation, cell growth viability and invasion, and the induction of cell apoptosis. In accordance with the effect of miR-145 on cell growth, miR-145 suppresses tumor growth in vivo. MiR-145 is found to negatively regulate P70S6K1 and MUC1 protein levels by directly targeting their 3?UTRs. Importantly, the overexpression of p70S6K1 and MUC1 can restore the cell colony formation and invasion abilities that are reduced by miR-145, respectively. MiR-145 expression is increased after 5-aza-CdR treatment, and 5-aza-CdR treatment results in the same phenotype as the effect of miR-145 overexpression. Our study suggests that miR-145 modulates ovarian cancer growth and invasion by suppressing p70S6K1 and MUC1, functioning as a tumor suppressor. Moreover, our data imply that miR-145 has potential as a miRNA-based therapeutic target for ovarian cancer.

  19. Protein kinase D1 stimulates proliferation and enhances tumorigenesis of MCF-7 human breast cancer cells through a MEK/ERK-dependent signaling pathway

    SciTech Connect (OSTI)

    Karam, Manale; Legay, Christine; Auclair, Christian; Ricort, Jean-Marc, E-mail: jean-marc.ricort@univ-montp2.fr

    2012-03-10T23:59:59.000Z

    Protein kinase D1, PKD1, is a novel serine/threonine kinase whose altered expression and dysregulation in many tumors as well as its activation by several mitogens suggest that this protein could regulate proliferation and tumorigenesis. Nevertheless, the precise signaling pathways used are still unclear and the potential direct role of PKD1 in tumor development and progression has not been yet investigated. In order to clarify the role of PKD1 in cell proliferation and tumorigenesis, we studied the effects of PKD1 overexpression in a human adenocarcinoma breast cancer cell line, MCF-7 cells. We demonstrated that overexpression of PKD1 specifically promotes MCF-7 cell proliferation through accelerating G0/G1 to S phase transition of the cell cycle. Moreover, inhibition of endogenous PKD1 significantly reduced cell proliferation. Taken together, these results clearly strengthen the regulatory role of PKD1 in cell growth. We also demonstrated that overexpression of PKD1 specifically diminished serum- and anchorage-dependence for proliferation and survival in vitro and allowed MCF-7 cells to form tumors in vivo. Thus, all these data highlight the central role of PKD1 in biological processes which are hallmarks of malignant transformation. Analysis of two major signaling pathways implicated in MCF-7 cell proliferation showed that PKD1 overexpression significantly increased ERK1/2 phosphorylation state without affecting Akt phosphorylation. Moreover, PKD1 overexpression-stimulated cell proliferation and anchorage-independent growth were totally impaired by inhibition of the MEK/ERK kinase cascade. However, neither of these effects was affected by blocking the PI 3-kinase/Akt signaling pathway. Thus, the MEK/ERK signaling appears to be a determining pathway mediating the biological effects of PKD1 in MCF-7 cells. Taken together, all these data demonstrate that PKD1 overexpression increases the aggressiveness of MCF-7 breast cancer cells through enhancing their oncogenic properties and would, therefore, define PKD1 as a potentially new promising anti-tumor therapeutic target.

  20. Nonstochastic effects of different energy beta emitters on pig skin

    SciTech Connect (OSTI)

    Peel, D.M.; Hopewell, J.W.; Wells, J.; Charles, M.W.

    1984-08-01T23:59:59.000Z

    Circular areas of pig skin from 1- to 40-mm diameter were irradiated with ..beta.. emitters of high, medium, and low energies, /sup 90/Sr, /sup 170/Tm, and /sup 147/Pm, respectively. The study provides information for radiological protection problems of localized skin exposures. During the first 16 weeks after irradiation /sup 90/Sr produced a first reaction due to epithelial cell death followed by a second reaction attributable to damage to the dermal blood vessels. /sup 170/Tm and /sup 147/Pm produced the epithelial reaction only. The epithelial dose response varied as a function of ..beta.. energy. The doses required to produce moist desquamation in 50% of 15- to 22.5-mm fields (ED/sub 50/) were 30-45 Gy from/sup 90/Sr, approx.80 Gy from /sup 170/Tm, and approx.500 Gy from /sup 147/Pm. An area effect was observed in the epithelial response to /sup 90/Sr irradiation. The ED/sub 50/ for moist desquamation ranged from approx.25 Gy for a 40-mm source to approx.450 Gy for a 1-mm source. It is also suggested that the area effects could be explained by different modes of epithelial repopulation after irradiation.

  1. Active skin for turbulent drag reduction

    E-Print Network [OSTI]

    Mani, Raghavendran

    2002-01-01T23:59:59.000Z

    pursued is "micro" in the sense that only micro-scale wave amplitudes (order of 30[]m) and energy inputs are sufficient to produce significant benefits. Two actuation principles are proposed and analyzed and different skin designs based on these two...

  2. Preventive Skin Care Fact or Fiction?

    E-Print Network [OSTI]

    Goldman, Steven A.

    and colors Many are birthmarks http://www.skinsight.com/images/dx/webInfant/congenitalMelanocyticNevus_33234 by skin biopsy to make sure not cancer http://www.skinsight.com/images/dx/webInfant/congenital://www.skincancer.org/understanding-uva-and-uvb.html #12;Practice GOOD habits! · Reapply sunscreen if: ­ Sweating ­ Swimming in water ­ Doing any activity

  3. The accumulations of HIF-1? and HIF-2? by JNK and ERK are involved in biphasic effects induced by different levels of arsenite in human bronchial epithelial cells

    SciTech Connect (OSTI)

    Xu, Yuan; Li, Yuan [Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China) [Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); Li, Huiqiao [Qujing Center for Disease Control and Prevention, Qujing 655000, Yunnan (China)] [Qujing Center for Disease Control and Prevention, Qujing 655000, Yunnan (China); Pang, Ying; Zhao, Yue; Jiang, Rongrong; Shen, Lu [Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China) [Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); Zhou, Jianwei; Wang, Xinru [The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China)] [The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); Liu, Qizhan, E-mail: drqzliu@hotmail.com [Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China) [Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China)

    2013-01-15T23:59:59.000Z

    The biphasic effects of arsenite, in which low levels of arsenite induce cell proliferation and high levels of arsenite induce DNA damage and apoptosis, apparently contribute to arsenite-induced carcinogenesis. However, the mechanisms underlying this phenomenon are not well understood. In this study, we investigated the effects of different levels of arsenite on cell proliferation, DNA damage and apoptosis as well as on signal transduction pathways in human bronchial epithelial (HBE) cells. Our results show that a low level of arsenite activates extracellular signal-regulated kinases (ERK), which probably mediate arsenite-inhibited degradation of ubiquitinated hypoxia-inducible factor-2? (HIF-2?) in HBE cells. ERK inhibition blocks cell proliferation induced by a low level of arsenite, in part via HIF-2?. In contrast, a high level of arsenite activates c-Jun N-terminal kinases (JNK), which provoke a response to suppress ubiquitinated HIF-1? degradation. Down-regulation of HIF-1? by inhibiting JNK, however, increases the DNA damage but decreases the apoptosis induced by a high level of arsenite. Thus, data in the present study suggest that the accumulations of HIF-1? and HIF-2? by JNK and ERK are involved in different levels of arsenite-induced biphasic effects, with low levels of arsenite inducing cell proliferation and high levels of arsenite inducing DNA damage and apoptosis in HBE cells. -- Highlights: ? Biphasic effects induced by different concentrations of arsenite. ? Different regulation of ERK or JNK signal pathway by arsenite. ? Different regulation of HIF1? or HIF 2? by arsenite.

  4. 4-Hydroxyestradiol induces oxidative stress and apoptosis in human mammary epithelial cells: possible protection by NF-{kappa}B and ERK/MAPK

    SciTech Connect (OSTI)

    Chen Zhihua [National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, Seoul 151-742 (Korea, Republic of); Na, Hye-Kyung [National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, Seoul 151-742 (Korea, Republic of); Hurh, Yeon-Jin [National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, Seoul 151-742 (Korea, Republic of); Surh, Young-Joon [National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, Seoul 151-742 (Korea, Republic of)]. E-mail: surh@plaza.snu.ac.kr

    2005-10-01T23:59:59.000Z

    Catechol estrogens, the hydroxylated metabolites of 17{beta}-estradiol (E{sub 2}), have been considered to be implicated in estrogen-induced carcinogenesis. 4-Hydroxyestradiol (4-OHE{sub 2}), an oxidized metabolite of E{sub 2} formed preferentially by cytochrome P450 1B1, reacts with DNA to form depurinating adducts thereby exerting genotoxicity and carcinogenicity. 4-OHE{sub 2} undergoes 2-electron oxidation to quinone via semiquinone, and during this process, reactive oxygen species (ROS) can be generated to cause DNA damage and cell death. In the present study, 4-OHE{sub 2} was found to elicit cytotoxicity in cultured human mammary epithelial (MCF-10A) cells, which was blocked by the antioxidant trolox. MCF-10A cells treated with 4-OHE{sub 2} exhibited increased intracellular ROS accumulation and 8-oxo-7,8-dihydroxy-2'-deoxyguanosine formation, and underwent apoptosis as determined by poly(ADP-ribose)polymerase cleavage and disruption of mitochondrial transmembrane potential. The redox-sensitive transcription factor nuclear factor {kappa}B (NF-{kappa}B) was transiently activated by 4-OHE{sub 2} treatment. Cotreatment of MCF-10A cells with the NF-{kappa}B inhibitor, L-1-tosylamido-2-phenylethyl chloromethyl ketone, exacerbated 4-OHE{sub 2}-induced cell death. 4-OHE{sub 2} also caused transient activation of extracellular signal-regulated protein kinases (ERK) involved in transmitting cell survival or death signals. A pharmacological inhibitor of ERK aggravated the 4-OHE{sub 2}-induced cytotoxicity, supporting the pivotal role of ERK in protecting against catechol estrogen-induced oxidative cell death.

  5. Vaccine delivery with microneedle skin patches in nonhuman primates

    E-Print Network [OSTI]

    Li, Adrienne V

    Transcutaneous drug delivery from planar skin patches is effective for small-molecule drugs and skin-permeable vaccine adjuvants. However, to achieve efficient delivery of vaccines and other macromolecular therapeutics ...

  6. Expression of the UL16 glycoprotein of Human Cytomegalovirus protects the virus-infected cell from attack by natural killer cells

    E-Print Network [OSTI]

    Vales-Gomez, Mar; Browne, Helena; Reyburn, Hugh T

    2003-03-14T23:59:59.000Z

    :238-241 4. Reddehase MJ, Weiland F, Munch K, Jonjic S, Luske A and Koszi- nowski UH Interstitial murine cytomegalovirus pneumonia after irradiation: characterization of cells that limit viral rep- lication during established infection of the lungs J Virol...

  7. The study of skin permeation mechanism and terpene-skin lipid interaction via nuclear magnetic resonance

    E-Print Network [OSTI]

    Lim, P. F. C.; Liu, Xiang Yang; Huang, Meng; Ho, P. C. L.; Chan, S. Y.

    2006-10-27T23:59:59.000Z

    , lipid extraction, etc. In our case, the interaction between a terpene and a lipid was examinedwith nuclear magnetic resonance (NMR), which aims to provide some insight to enhancement in skin permeation. Palmitic acid (Fig 1), a 16-carbon fatty acid... and oxides were able to producea greater ??. National University of Singapore, 2006 PS77 -The Study of Skin Permeation Mechanism and Terpene-Lipid Interaction via Nuclear Magnetic Resonance Perry Fung Chye Lim a, Xiang Yang Liu b, Meng Huang a, Paul Chi...

  8. Effects of oncogenic Ras and p38 mitogen-activated protein kinase on the adhesion of normal human cells

    E-Print Network [OSTI]

    Waldman, Lynne K

    2010-01-01T23:59:59.000Z

    Activating mutations in RAS oncogenes commonly arise in human cancers. However, in experimental settings, oncogenic RAS has most often been studied at supraphysiological levels of expression. Importantly, work by others ...

  9. Circulating proteolytic signatures of chemotherapy-induced cell death in humans discovered by N-terminal labeling

    E-Print Network [OSTI]

    Wiita, AP; Hsu, GW; Lu, CM; Esensten, JH; Wells, JA

    2014-01-01T23:59:59.000Z

    JA (2010) Sampling the N-terminal proteome of human blood.B, Sherman F (2003) N-terminal acetyltransferases andrequire- ments for N-terminal acetylation of eukaryotic

  10. Mechanisms of hormonal regulation of CAD gene expression and inhibition by Aryl hydrocarbon receptor agonist in human breast cancer cells 

    E-Print Network [OSTI]

    Khan, Shaheen Munawar Ali

    2007-04-25T23:59:59.000Z

    The CAD gene is trifunctional and expresses carbamoylphosphate synthetase/aspartate carbamyltransferase/dihydroorotase, which are required for pyrimidine biosynthesis. CAD gene activities are induced in MCF-7 human breast ...

  11. SUPPLEMENTAL FUNDING ANNOUNCEMENT CAREER DEVELOPMENT AWARD IN MELANOMA & SKIN CANCER

    E-Print Network [OSTI]

    Sibille, Etienne

    SUPPLEMENTAL FUNDING ANNOUNCEMENT CAREER DEVELOPMENT AWARD IN MELANOMA & SKIN CANCER Sponsored by: The Specialized Program of Research Excellence (SPORE) in Melanoma & Skin Cancer University of Pittsburgh Cancer Institute Purpose The overall goals of the Melanoma & Skin Cancer SPORE are to improve the detection

  12. FUNDING ANNOUNCEMENT CAREER DEVELOPMENT AWARD IN MELANOMA & SKIN CANCER

    E-Print Network [OSTI]

    Sibille, Etienne

    FUNDING ANNOUNCEMENT CAREER DEVELOPMENT AWARD IN MELANOMA & SKIN CANCER Sponsored by: The Specialized Program of Research Excellence (SPORE) in Melanoma & Skin Cancer University of Pittsburgh Cancer Institute (UPCI) Purpose The overall goals of the Melanoma & Skin Cancer SPORE are to improve the detection

  13. absorption skin: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    absorption skin First Page Previous Page 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Next Page Last Page Topic Index 1 Healthy Skin Matters Normal Skin...

  14. Ran GTPase protein promotes human pancreatic cancer proliferation by deregulating the expression of Survivin and cell cycle proteins

    SciTech Connect (OSTI)

    Deng, Lin [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi 710032 (China) [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi 710032 (China); Department of Oncology, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi 710038 (China); Lu, Yuanyuan; Zhao, Xiaodi; Sun, Yi; Shi, Yongquan; Fan, Hongwei; Liu, Changhao; Zhou, Jinfeng; Nie, Yongzhan; Wu, Kaichun [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi 710032 (China)] [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi 710032 (China); Fan, Daiming, E-mail: daimingfan@fmmu.edu.cn [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi 710032 (China)] [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi 710032 (China); Guo, Xuegang, E-mail: xuegangguo@126.com [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi 710032 (China)] [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi 710032 (China)

    2013-10-18T23:59:59.000Z

    Highlights: •Overexpression of Ran in pancreatic cancer was correlated with histological grade. •Downregulation of Ran could induce cell apoptosis and inhibit cell proliferation. •The effects were mediated by cell cycle proteins, Survivin and cleaved Caspase-3. -- Abstract: Ran, a member of the Ras GTPase family, has important roles in nucleocytoplasmic transport. Herein, we detected Ran expression in pancreatic cancer and explored its potential role on tumour progression. Overexpressed Ran in pancreatic cancer tissues was found highly correlated with the histological grade. Downregulation of Ran led to significant suppression of cell proliferation, cell cycle arrest at the G1/S phase and induction of apoptosis. In vivo studies also validated that result. Further studies revealed that those effects were at least partly mediated by the downregulation of Cyclin A, Cyclin D1, Cyclin E, CDK2, CDK4, phospho-Rb and Survivin proteins and up regulation of cleaved Caspase-3.

  15. Hypoxia-inducible factor-1? (HIF-1?) is upregulated in a HIF-1?-dependent manner in 518A2 human melanoma cells under hypoxic conditions

    SciTech Connect (OSTI)

    Mandl, Markus, E-mail: mmandl@mail.austria.com; Kapeller, Barbara; Lieber, Roman; Macfelda, Karin

    2013-04-26T23:59:59.000Z

    Highlights: •HIF-1? is a hypoxia-responsive protein in 518A2 human melanoma cells. •HIF-1? is upregulated in a HIF-1?-dependent manner under hypoxic conditions. •HIF-1? is not elevated due to heterodimerization with HIF-1? per se. •HIF-1? inducibility has a biological relevance as judged in Het-CAM model. -- Abstract: Solid tumors include hypoxic areas due to excessive cell proliferation. Adaptation to low oxygen levels is mediated by the hypoxia-inducible factor (HIF) pathway promoting invasion, metastasis, metabolic alterations, chemo-resistance and angiogenesis. The transcription factor HIF-1, the major player within this pathway consists of HIF-1? and HIF-1?. The alpha subunit is continuously degraded under normoxia and becomes stabilized under reduced oxygen supply. In contrast, HIF-1? is generally regarded as constitutively expressed and being present in excess within the cell. However, there is evidence that the expression of this subunit is more complex. The aim of this study was to investigate the role of HIF-1? in human melanoma cells. Among a panel of five different cell lines, in 518A2 cells exposed to the hypoxia-mimetic cobalt chloride HIF-1? was rapidly elevated on protein level. Knockdown experiments performed under cobalt chloride-exposure and hypoxia revealed that this effect was mediated by HIF-1?. The non-canonical relationship between these subunits was further confirmed by pharmacologic inhibition of HIF-1? and by expression of a dominant-negative HIF mutant. Overexpression of HIF-1? showed a time delay in HIF-1? induction, thus arguing for HIF-1? de novo synthesis rather than protein stabilization by heterodimerization. A Hen’s egg test-chorioallantoic membrane model of angiogenesis and invasion indicated a local expression of HIF-1? and implies a biological relevance of these findings. In summary, this study demonstrates the HIF-1?-dependent regulation of HIF-1? under hypoxic conditions for the first time. The results indicate a novel cell specific mechanism which might prevent HIF-1? to become a limiting factor.

  16. Maturation of the viral core enhances the fusion of HIV-1 particles with primary human T cells and monocyte-derived macrophages

    SciTech Connect (OSTI)

    Jiang Jiyang [Department of Microbiology and Immunology, Vanderbilt University School of Medicine, A-5301 Medical Center North, Nashville, TN 37232-2363 (United States); Aiken, Christopher [Department of Microbiology and Immunology, Vanderbilt University School of Medicine, A-5301 Medical Center North, Nashville, TN 37232-2363 (United States)]. E-mail: chris.aiken@vanderbilt.edu

    2006-03-15T23:59:59.000Z

    HIV-1 infection requires fusion of viral and cellular membranes in a reaction catalyzed by the viral envelope proteins gp120 and gp41. We recently reported that efficient HIV-1 particle fusion with target cells is linked to maturation of the viral core by an activity of the gp41 cytoplasmic domain. Here, we show that maturation enhances the fusion of a variety of recombinant viruses bearing primary and laboratory-adapted Env proteins with primary human CD4{sup +} T cells. Overall, HIV-1 fusion was more dependent on maturation for viruses bearing X4-tropic envelope proteins than for R5-tropic viruses. Fusion of HIV-1 with monocyte-derived macrophages was also dependent on particle maturation. We conclude that the ability to couple fusion to particle maturation is a common feature of HIV-1 Env proteins and may play an important role during HIV-1 replication in vivo.

  17. Inactivation of human osteosarcoma cells in vitro by {sup 211}At-TP-3 monoclonal antibody: Comparison with astatine-211 and external-beam X rays

    SciTech Connect (OSTI)

    Larsen, R.H. [Univ. of Oslo (Norway)]|[Institute for Cancer Research, Oslo (Norway); Bruland, O.S. [Institute for Cancer Research, Oslo (Norway); Hoff, P.; Alstad, J. [Univ. of Oslo (Norway); Lindmo, T. [Institute for Cancer Research, Oslo (Norway); Rofstad, E.K. [Norwegian Institute of Technology, Trondheim (Norway)

    1994-08-01T23:59:59.000Z

    The potential usefulness of {alpha}-particle radioimmunotherapy in the treatment of osteosarcoma was studied in vitro by using the monoclonal antibody TP-3 and cells of three human osteosarcoma cell lines (OHS, SAOS and KPDX) differing in antigen expression. Cell survival curves were established after treatment with (a) {sup 211}At-TP-3 of different specific activities, (b) {sup 211}At-labeled bovine serum albumin (BSA), (c) free {sup 211}At and (d) external-beam X rays. The three osteosarcoma cell lines showed similar survival curves, whether treated with external-beam X rays, {sup 211}At-BSA or free {sup 211}At. The D{sub o}`s were lower for free {sup 211}At than for {sup 211}At-BSA. The survival curves for {sup 211}At-TP-3 treatment, on the other hand, differed significantly among the cell lines, suggesting that sensitivity to {sup 211}At-TP-3 treatment was governed by cellular properties other than sensitivity to external-beam X rays. The cellular property most important for sensitivity to {sup 211}At-TP-3 treatment was the antigen expression. Cell inactivation after {sup 211}At-TP-3 treatment increased substantially with increasing specific activity of the {sup 211}At-TP-3. At high specific activities, the cytotoxic effect of {sup 211}At-TP-3 was significantly higher than that of {sup 211}At-BSA. In conclusion, {sup 211}At-TP-3 has the potential to give clinically favorable therapeutic ratios in the treatment of osteosarcoma. 39 refs., 5 figs., 2 tabs.

  18. Generation and characterization of transgene-free human induced pluripotent stem cells and conversion to putative clinical-grade status

    E-Print Network [OSTI]

    2013-01-01T23:59:59.000Z

    Cell 2010, 7:618–630. 15. Sommer CA, Stadtfeld M, Murphy GJ,27:543–549. 16. Somers A, Jean JC, Sommer CA, Omari A, FordCC, Mills JA, Ying L, Sommer AG, Jean JM, Smith BW, Lafyatis

  19. Isolation and effects of citrus limonoids on cytochrome p450 inhibition, apoptotic induction and cytotoxicity on human cancer cells.

    E-Print Network [OSTI]

    Poulose, Shibu M.

    2007-04-25T23:59:59.000Z

    -2) cells. The first study developed a bulk purification method for limonoids, from seeds and molasses of citrus fruits, using a combination of chromatographic techniques. This also resulted in an efficient purification method for naringin...

  20. Evaluation of the sensitizing potential of antibiotics in vitro using the human cell lines THP-1 and MUTZ-LC and primary monocyte?derived dendritic cells

    SciTech Connect (OSTI)

    Sebastian, Katrin, E-mail: ksebastian@ukaachen.de [Department of Dermatology and Allergology, RWTH Aachen University Hospital, D-52074 Aachen (Germany)] [Department of Dermatology and Allergology, RWTH Aachen University Hospital, D-52074 Aachen (Germany); Ott, Hagen [Department of Dermatology and Allergology, RWTH Aachen University Hospital, D-52074 Aachen (Germany)] [Department of Dermatology and Allergology, RWTH Aachen University Hospital, D-52074 Aachen (Germany); Zwadlo-Klarwasser, Gabriele [IZKF (BIOMAT), RWTH Aachen University Hospital, D-52074 Aachen (Germany)] [IZKF (BIOMAT), RWTH Aachen University Hospital, D-52074 Aachen (Germany); Skazik-Voogt, Claudia; Marquardt, Yvonne; Czaja, Katharina; Merk, Hans F.; Baron, Jens Malte [Department of Dermatology and Allergology, RWTH Aachen University Hospital, D-52074 Aachen (Germany)] [Department of Dermatology and Allergology, RWTH Aachen University Hospital, D-52074 Aachen (Germany)

    2012-08-01T23:59:59.000Z

    Since the 7th amendment to the EU cosmetics directive foresees a complete ban on animal testing, alternative in vitro methods have been established to evaluate the sensitizing potential of small molecular weight compounds. To find out whether these novel in vitro assays are also capable to predict the sensitizing potential of small molecular weight drugs, model compounds such as beta-lactams and sulfonamides – which are the most frequent cause of adverse drug reactions – were co-incubated with THP-1, MUTZ-LC, or primary monocyte?derived dendritic cells for 48 h and subsequent expression of selected marker genes (IL-8, IL-1?, CES1, NQO1, GCLM, PIR and TRIM16) was studied by real time PCR. Benzylpenicillin and phenoxymethylpenicillin were recognized as sensitizing compounds because they are capable to induce the mRNA expression of these genes in moDCs and, except for IL-8, in THP-1 cells but not in MUTZ-LC. Ampicillin stimulated the expression of some marker genes in moDCs and THP-1 cells. SMX did not affect the expression of these genes in THP-1, however, in moDCs, at least PIR was enhanced and there was an increase of the release of IL-8. These data reveal that novel in vitro DC based assays might play a role in the evaluation of the allergenic potential of novel drug compounds, but these systems seem to lack the ability to detect the sensitizing potential of prohaptens that require metabolic activation prior to sensitization and moDCs seem to be superior with regard to the sensitivity compared with THP-1 and MUTZ-3 cell lines. -- Highlights: ? We tested the sensitizing potential of small molecular weight drugs in vitro. ? In vitro assays were performed with moDCs and THP-1 cells. ? Beta-lactam antibiotics can be recognized as sensitizing compounds. ? They affect the expression of metabolic enzymes, cytokines and transcription factors. ? Sulfamethoxazole has no measurable effect on THP-1 cells and moDCs.

  1. DNA Double-Strand Breaks Form in Bystander Cells after Microbeam Irradiation of Three-dimensional Human Tissue Models

    E-Print Network [OSTI]

    Brenner, David Jonathan

    Research Accelerator Facility, Center for Radiological Research, College of Physicians and Surgeons Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada; and 3 Radiological implications for cancer radiother- apy and diagnostic radiology as well as for human health in general

  2. miR-421 induces cell proliferation and apoptosis resistance in human nasopharyngeal carcinoma via downregulation of FOXO4

    SciTech Connect (OSTI)

    Chen, Liang [Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Zhujiang Hospital of Southern Medical University, Guangzhou 510282 (China) [Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Zhujiang Hospital of Southern Medical University, Guangzhou 510282 (China); Department of Otolaryngology, Guangzhou General Hospital of PLA Guangzhou Command, Guangzhou 510010 (China); Tang, Yanping [Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Zhujiang Hospital of Southern Medical University, Guangzhou 510282 (China)] [Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Zhujiang Hospital of Southern Medical University, Guangzhou 510282 (China); Wang, Jian [Department of Otolaryngology, Guangzhou General Hospital of PLA Guangzhou Command, Guangzhou 510010 (China)] [Department of Otolaryngology, Guangzhou General Hospital of PLA Guangzhou Command, Guangzhou 510010 (China); Yan, Zhongjie [Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing PLA,The Bayi Clinical Medical Institute of Southern Medical University, Beijing 100700 (China)] [Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing PLA,The Bayi Clinical Medical Institute of Southern Medical University, Beijing 100700 (China); Xu, Ruxiang, E-mail: RuxiangXu@yahoo.com [Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing PLA,The Bayi Clinical Medical Institute of Southern Medical University, Beijing 100700 (China)] [Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing PLA,The Bayi Clinical Medical Institute of Southern Medical University, Beijing 100700 (China)

    2013-06-14T23:59:59.000Z

    Highlights: •miR-421 is upregulated in nasopharyngeal carcinoma. •miR-421 induces cell proliferation and apoptosis resistance. •FOXO4 is a direct and functional target of miR-421. -- Abstract: microRNAs have been demonstrated to play important roles in cancer development and progression. Hence, identifying functional microRNAs and better understanding of the underlying molecular mechanisms would provide new clues for the development of targeted cancer therapies. Herein, we reported that a microRNA, miR-421 played an oncogenic role in nasopharyngeal carcinoma. Upregulation of miR-421 induced, whereas inhibition of miR-421 repressed cell proliferation and apoptosis resistance. Furthermore, we found that upregulation of miR-421 inhibited forkhead box protein O4 (FOXO4) signaling pathway following downregulation of p21, p27, Bim and FASL expression by directly targeting FOXO4 3?UTR. Additionally, we demonstrated that FOXO4 expression is critical for miR-421-induced cell growth and apoptosis resistance. Taken together, our findings not only suggest that miR-421 promotes nasopharyngeal carcinoma cell proliferation and anti-apoptosis, but also uncover a novel regulatory mechanism for inactivation of FOXO4 in nasopharyngeal carcinoma.

  3. Inhibition of the ERK phosphorylation plays a role in terbinafine-induced p21 up-regulation and DNA synthesis inhibition in human vascular endothelial cells

    SciTech Connect (OSTI)

    Ho, P.-Y. [Graduate Institute of Cell and Molecular Biology, Taipei Medical University, Taipei, Taiwan (China); Hsu, S.-P. [Institute of Physiology, College of Medicine, National Taiwan University, Taiwan (China); Liang, Y.-C. [Graduate Institute of Biomedical Technology, Taipei Medical University, Taipei, Taiwan (China); Kuo, M.-L. [Institute of Toxicology, College of Medicine, National Taiwan University, Taiwan (China); Ho, Y.-S. [Graduate Institute of Biomedical Technology, Taipei Medical University, Taipei, Taiwan (China); Lee, W.-S. [Graduate Institute of Neuroscience, Taipei Medical University, Taipei, Taiwan (China); Graduate Institute of Medical Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan (China); Department of Physiology, Medical College, Taipei Medical University, Taipei, Taiwan (China)], E-mail: wslee@tmu.edu.tw

    2008-05-15T23:59:59.000Z

    Previously, we showed that terbinafine (TB) induces cell-cycle arrest in cultured human umbilical vein endothelial cells (HUVEC) through an up-regulation of the p21 protein. The aim of this study is to delineate the molecular mechanisms underlying TB-induced increase of p21 protein. RT-PCR analysis demonstrated that the mRNA levels of p21 and p53 were increased in the TB-treated HUVEC. The p21 promoter activity was also increased by TB treatment. Transfection of HUVEC with p53 dominant negative (DN) abolished the TB-induced increases of p21 promoter activity and protein level, suggesting that the TB-induced increase of p21 is p53-dependent. Western blot analysis demonstrated that TB decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK). Over-expression of mitogen-activated protein kinase (MEK)-1, the immediate upstream activator kinase of ERK, abolished the TB-induced increases of p21 and p53 protein and decrease of thymidine incorporation. The ERK inhibitor (PD98059) enhanced the TB-induced inhibition of thymidine incorporation into HUVEC. Taken together, these data suggest that the decrease of ERK activity plays a role in the TB-induced up-regulation of p21 in HUVEC. On the other hand, pretreatment of the cells with geranylgeraniol (GGOH), farnesol (FOH), or Ras inhibitor peptide did not affect the TB-induced decrease of thymidine incorporation. Taken together, our results suggest that TB might cause a decrease of MEK, which in turn up-regulates p53 through the inhibition of ERK phosphorylation, and finally causes an increase of p21 expression and cell-cycle arrest.

  4. Turbine blade having a constant thickness airfoil skin

    DOE Patents [OSTI]

    Marra, John J

    2012-10-23T23:59:59.000Z

    A turbine blade is provided for a gas turbine comprising: a support structure comprising a base defining a root of the blade and a framework extending radially outwardly from the base, and an outer skin coupled to the support structure framework. The skin has a generally constant thickness along substantially the entire radial extent thereof. The framework and the skin define an airfoil of the blade.

  5. Orai1 Function is Essential for T Cell Homing to Lymph Nodes

    E-Print Network [OSTI]

    Greenberg, Milton L.; Yu, Ying; Leverrier, Sabrina; Zhang, Shenyuan L.; Parker, Ian; Cahalan, Michael D.

    2013-01-01T23:59:59.000Z

    Biotech). In some experiments, human CD3 + T cells were7 human PBL were injected intraperitoneally and experimentsindicated. Human cells were used for experiments 24 hr after

  6. Topical treatment of melanoma skin metastases with Imiquimod: a review

    E-Print Network [OSTI]

    Sisti, Andrea; Sisti, Giovanni; Oranges, Carlo Maria

    2015-01-01T23:59:59.000Z

    locoregional recurrences of melanoma: a new therapeuticthe treatment of metastatic melanoma to skin. Arch Dermatol,High W, and Stewart L, Melanoma in situ treated successfully

  7. allotransplanted vascularized skin: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    1 Optimum pulse duration and radiant exposure for vascular laser therapy of dark port-wine skin: a theoretical study Engineering Websites Summary: Optimum pulse duration and...

  8. analyzing skin conductance: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    coupling between each tactile sensing chip and a ground Shinoda, Hiroyuki 8 HandWave: Design and Manufacture of a Wearable Wireless Skin Conductance Computer Technologies and...

  9. Genetic manipulation of Fezf2 in human embryonic stem cells and its application in studying central nervous system development and repair

    E-Print Network [OSTI]

    Ruby, Katherine Marie

    2011-01-01T23:59:59.000Z

    passed through a 40 ?m cell strainer (BD Falcon) to create apassed through a 40µM cell strainer. To remove dead cells

  10. RESEARCH Open Access Cellular transcriptional profiling in human lung

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    RESEARCH Open Access Cellular transcriptional profiling in human lung epithelial cells infected expression profiles of human lung A549 cells infected by five different subtypes of human and avian influenza

  11. Development of a combined model of tissue kinetics and radiation response of human bronchiolar epithelium with single cell resolution

    E-Print Network [OSTI]

    Ostrovskaya, Natela Grigoryevna

    2006-10-30T23:59:59.000Z

    cells of the airways due to internal exposure to alpha-particle emitters, e.g. radon. Inhalation of radon, a colorless and odorless gas, one of the products of the decay of uranium which occurs naturally in the earth?s crust, is the second major cause... epithelial tissue plays an important role in normal lung physiology. square4 lung epithelia are target tissues for occupational internal exposures and for radon exposure (26); square4 the epithelium of bronchioles appears to be the origin...

  12. Inhibition of KCa3.1 by depolarisation and 2-aminoethoxydiphenyl borate (2-APB) during Ca2+ release activated Ca2+ (CRAC) entry in human erythroleukemia (HEL) cells: Implications for the interpretation of 2-APB inhibition of CRAC entry

    E-Print Network [OSTI]

    Littlechild, Robert; Zaidman, Nathalie; Khodaverdi, Darren; Mason, Michael James

    2014-12-23T23:59:59.000Z

    -mediated Ca2+ oscillations and oscillations in KCa3.1 activity [30,31,32]. Following transition to the whole cell configuration the cell was held at -80 mV and 200 ms voltage ramps from -100 to +100 mV 18 administered every three seconds. The magnitude... ], voltage-gated K+ channels [10], the non-selective cation channel TRPM7 [11], a Mg2+-inhibited K+ conductance described in human erythroleukemia (HEL) cells [12] and mitochondrial Ca2+ release [7]. Although it is well established to block CRAC currents...

  13. Parsing ERK Activation Reveals Quantitatively Equivalent Contributions From Epidermal Growth Factor Receptor and HER2 In Human Mammary Epithelial Cells

    SciTech Connect (OSTI)

    Hendriks, Bart S.; Orr, Galya; Wells, Alan H.; Wiley, H. S.; Lauffenburger, Douglas A.

    2005-02-18T23:59:59.000Z

    HER2, a member of the EGFR tyrosine kinase family, functions as an accessory EGFR signaling component and alters EGFR trafficking by heterodimerization. HER2 overexpression leads to aberrant cell behavior including enhanced proliferation and motility. Here we apply a combination of computational modeling and quantitative experimental studies of the dynamic interactions between EGFR and HER2, and their downstream activation of extracellular signal-related kinase (ERK) to understand this complex signaling system. Using cells expressing different levels of HER2 relative to the EGFR, we can separate relative contributions of EGFR and HER2 to signaling amplitude and duration. Based on our model calculations, we demonstrate that, in contrast with previous suggestions in the literature, the intrinsic capabilities of EGFR and HER2 to activated ERK are quantitatively equivalent . We find that HER2-mediated effects on EGFR dimerization and trafficking are sufficient to explain the detected HER2-mediated amplification of EGF-induced ERK signaling. Our model suggests that transient amplification of ERK activity by HER2 arises predominantly from the 2-to-1 stoichiometry of receptor kinase to bound ligand in EGFR/HER2 heterodimers compared to the 1-to-1 stoichiometry of the EGFR homodimer, but alterations in receptor trafficking, with resultant EGFR sparing, cause the sustained HER2-mediated enhancement of ERK signaling.

  14. Laminin peptide YIGSR induces collagen synthesis in Hs27 human dermal fibroblasts

    SciTech Connect (OSTI)

    Yoon, Jong Hyuk; Kim, Jaeyoon; Lee, Hyeongjoo [NovaCell Technology Inc., Pohang, Kyungbuk 790-784 (Korea, Republic of)] [NovaCell Technology Inc., Pohang, Kyungbuk 790-784 (Korea, Republic of); Kim, So Young [Department of Dermatology, Chung-Ang University College of Medicine, Seoul 156-756 (Korea, Republic of) [Department of Dermatology, Chung-Ang University College of Medicine, Seoul 156-756 (Korea, Republic of); Department of Convergence Medicine and Pharmaceutical Biosciences, Graduate School, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Jang, Hwan-Hee [Functional Food and Nutrition Division, Department of Agrofood Resources, Rural Development Administration, Suwon 441-853 (Korea, Republic of)] [Functional Food and Nutrition Division, Department of Agrofood Resources, Rural Development Administration, Suwon 441-853 (Korea, Republic of); Ryu, Sung Ho [Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Kyungbuk 790-784 (Korea, Republic of)] [Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Kyungbuk 790-784 (Korea, Republic of); Kim, Beom Joon [Department of Dermatology, Chung-Ang University College of Medicine, Seoul 156-756 (Korea, Republic of) [Department of Dermatology, Chung-Ang University College of Medicine, Seoul 156-756 (Korea, Republic of); Department of Convergence Medicine and Pharmaceutical Biosciences, Graduate School, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Lee, Taehoon G., E-mail: taehoon@novacelltech.com [NovaCell Technology Inc., Pohang, Kyungbuk 790-784 (Korea, Republic of)

    2012-11-23T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer We identify a function of the YIGSR peptide to enhance collagen synthesis in Hs27. Black-Right-Pointing-Pointer YIGSR peptide enhanced collagen type 1 synthesis both of gene and protein levels. Black-Right-Pointing-Pointer There were no changes in cell proliferation and MMP-1 level in YIGSR treatment. Black-Right-Pointing-Pointer The YIGSR effect on collagen synthesis mediated activation of FAK, pyk2 and ERK. Black-Right-Pointing-Pointer The YIGSR-induced FAK and ERK activation was modulated by FAK and MEK inhibitors. -- Abstract: The dermal ECM is synthesized from fibroblasts and is primarily compromised of fibrillar collagen and elastic fibers, which support the mechanical strength and resiliency of skin, respectively. Laminin, a major glycoprotein located in the basement membrane, promotes cell adhesion, cell growth, differentiation, and migration. The laminin tyrosine-isoleucine-glycine-serine-arginine (YIGSR) peptide, corresponding to the 929-933 sequence of the {beta}1 chain, is known to be a functional motif with effects on the inhibition of tumor metastasis, the regulation of sensory axonal response and the inhibition of angiogenesis through high affinity to the 67 kDa laminin receptor. In this study, we identified a novel function of the YIGSR peptide to enhance collagen synthesis in human dermal fibroblasts. To elucidate this novel function regarding collagen synthesis, we treated human dermal fibroblasts with YIGSR peptide in both a time- and dose-dependent manner. According to subsequent experiments, we found that the YIGSR peptide strongly enhanced collagen type 1 synthesis without changing cell proliferation or cellular MMP-1 level. This YIGSR peptide-mediated collagen type 1 synthesis was modulated by FAK inhibitor and MEK inhibitor. This study clearly reveals that YIGSR peptide plays a novel function on the collagen type 1 synthesis of dermal fibroblasts and also suggests that YIGSR is a strong candidate peptide for the treatment of skin aging and wrinkles.

  15. PASSAGE OF FISSION PRODUCTS THROUGH THE SKIN OF TUNA

    E-Print Network [OSTI]

    was slow. PASSAGE OF FISSION PRODUCTS THROUGH THE SKIN OF TUNA In relation to "fallout" from nuclear -bomb tests, it is of interest to measure the amounts of radioactive isotopes known to be present in mixtures of fission products which would pass through the skin of fish held under refrigera- tion on fishing vessels

  16. allergic skin test: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    allergic skin test First Page Previous Page 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Next Page Last Page Topic Index 1 The Skin Microbiome in Healthy and...

  17. Skin cancer detection by oblique-incidence diffuse reflectance spectroscopy

    E-Print Network [OSTI]

    Smith, Elizabeth Brooks

    2009-05-15T23:59:59.000Z

    Skin cancer is the most common form of cancer and it is on the rise. If skin cancer is diagnosed early enough, the survival rate is close to 90%. Oblique-incidence diffuse reflectance (OIR) spectroscopy offers a technology that may be used...

  18. INVESTIGATION The Lsktm1 Locus Modulates Lung and Skin

    E-Print Network [OSTI]

    Broman, Karl W.

    INVESTIGATION The Lsktm1 Locus Modulates Lung and Skin Tumorigenesis in the Mouse Antonella Galvan to both skin and lung tumorigenesis over the susceptibility of the SWR/J strain. In an effort to map tumor.93) and lung (LOD score = 8.74) tumorigenesis. Two genes, Igfbp5 and Igfbp2, residing in this locus

  19. Method and apparatus to measure the depth of skin burns

    DOE Patents [OSTI]

    Dickey, Fred M. (Albuquerque, NM); Holswade, Scott C. (Albuquerque, NM)

    2002-01-01T23:59:59.000Z

    A new device for measuring the depth of surface tissue burns based on the rate at which the skin temperature responds to a sudden differential temperature stimulus. This technique can be performed without physical contact with the burned tissue. In one implementation, time-dependent surface temperature data is taken from subsequent frames of a video signal from an infrared-sensitive video camera. When a thermal transient is created, e.g., by turning off a heat lamp directed at the skin surface, the following time-dependent surface temperature data can be used to determine the skin burn depth. Imaging and non-imaging versions of this device can be implemented, thereby enabling laboratory-quality skin burn depth imagers for hospitals as well as hand-held skin burn depth sensors the size of a small pocket flashlight for field use and triage.

  20. Integrated analysis reveals that STAT3 is central to the crosstalk between HER/ErbB receptor signaling pathways in human mammary epithelial cells

    SciTech Connect (OSTI)

    Gong, Chunhong; Zhang, Yi; Shankaran, Harish; Resat, Haluk

    2015-01-01T23:59:59.000Z

    Human epidermal growth factor receptors (HER, also known as ErbB) drive cellular proliferation, pro-survival and stress responses by activating several downstream kinases, in particular ERK, p38, JNK (SAPK), the PI3K/AKT, as well as various transcriptional regulators such as STAT3. When co-expressed, first three members of HER family (HER1-3) can form homo- and hetero-dimers. Based on the considerable evidence which suggest that every receptor dimer activates intracellular signaling pathways differentially, we hypothesized that the HER dimerization pattern is a better predictor of downstream signaling than the total receptor activation levels. We validated our hypothesis using a combination of model-based analysis to quantify the HER dimerization patterns and multi-factorial experiments where HER dimerization patterns and signaling crosstalk were rationally perturbed. We have measured the activation of HER1-3 receptors and of the sentinel signaling proteins ERK, AKT, p38, JNK, STAT3 as a function of time in a panel of human mammary epithelial (HME) cells expressing different levels of HER1-3 stimulated with various ligand combinations. Our analysis using multiple ways of clustering the activation data has confirmed that the HER receptor dimer is a better predictor of the signaling through p38, ERK and AKT pathways than the total HER receptor expression and activation levels. Targeted inhibition studies to identify the causal effects allowed us to obtain a consensus regulatory interaction model, which revealed that STAT3 occupies a central role in the crosstalk between the studied pathways.

  1. autologous fibrin-based skin: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    and Information Sciences Websites Summary: specialized sub- classes, namely "bikini" "porn" and "skin" "non-skin", respectively. The extracted pornographic image classifiers....

  2. atopic dermatitis-like skin: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    and Information Sciences Websites Summary: specialized sub- classes, namely "bikini" "porn" and "skin" "non-skin", respectively. The extracted pornographic image classifiers....

  3. acinetobacter baumannii-associated skin: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    and Information Sciences Websites Summary: specialized sub- classes, namely "bikini" "porn" and "skin" "non-skin", respectively. The extracted pornographic image classifiers....

  4. THE DYNAMIC RELATIONSHIP BETWEEN LANGERHANS CELLS AND INTRAEPIDERMAL NERVE FIBERS IN THE MOUSE AND RAT FOOTPAD

    E-Print Network [OSTI]

    Doss, Argenia Lanisha Necole

    2011-12-31T23:59:59.000Z

    Skin disorders are often associated with immune and nervous system dysfunction. Intraepidermal nerve fibers (IENFs) detect mechanical, thermal, and noxious stimuli. Although immune cells such as mast and T cells can alter ...

  5. Fibroblast growth factor 2 inhibits up-regulation of bone morphogenic proteins and their receptors during osteoblastic differentiation of human mesenchymal stem cells

    SciTech Connect (OSTI)

    Biver, Emmanuel, E-mail: ebiver@yahoo.fr [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France) [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France); Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex (France); Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14 (Switzerland); Soubrier, Anne-Sophie [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France) [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France); Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex (France); Thouverey, Cyril [Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14 (Switzerland)] [Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14 (Switzerland); Cortet, Bernard [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France) [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France); Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex (France); Broux, Odile [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France)] [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France); Caverzasio, Joseph [Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14 (Switzerland)] [Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14 (Switzerland); Hardouin, Pierre [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France)] [Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France)

    2012-11-02T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer FGF modulates BMPs pathway in HMSCs by down-regulating BMP/BMPR expression. Black-Right-Pointing-Pointer This effect is mediated by ERK and JNK MAPKs pathways. Black-Right-Pointing-Pointer Crosstalk between FGF and BMPs must be taken into account in skeletal bioengineering. Black-Right-Pointing-Pointer It must also be considered in the use of recombinant BMPs in orthopedic and spine surgeries. -- Abstract: Understanding the interactions between growth factors and bone morphogenic proteins (BMPs) signaling remains a crucial issue to optimize the use of human mesenchymal stem cells (HMSCs) and BMPs in therapeutic perspectives and bone tissue engineering. BMPs are potent inducers of osteoblastic differentiation. They exert their actions via BMP receptors (BMPR), including BMPR1A, BMPR1B and BMPR2. Fibroblast growth factor 2 (FGF2) is expressed by cells of the osteoblastic lineage, increases their proliferation and is secreted during the healing process of fractures or in surgery bone sites. We hypothesized that FGF2 might influence HMSC osteoblastic differentiation by modulating expressions of BMPs and their receptors. BMP2, BMP4, BMPR1A and mainly BMPR1B expressions were up-regulated during this differentiation. FGF2 inhibited HMSCs osteoblastic differentiation and the up-regulation of BMPs and BMPR. This effect was prevented by inhibiting the ERK or JNK mitogen-activated protein kinases which are known to be activated by FGF2. These data provide a mechanism explaining the inhibitory effect of FGF2 on osteoblastic differentiation of HMSCs. These crosstalks between growth and osteogenic factors should be considered in the use of recombinant BMPs in therapeutic purpose of fracture repair or skeletal bioengineering.

  6. Use of human bronchial epithelial cells (BEAS-2B) to study immunological markers resulting from exposure to PM{sub 2.5} organic extract from Puerto Rico

    SciTech Connect (OSTI)

    Fuentes-Mattei, Enrique, E-mail: enrique.fuentes@upr.ed [Department of Biochemistry, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan (Puerto Rico); Center for Environmental and Toxicological Research, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan (Puerto Rico); Rivera, Evasomary [Department of Biology, Rio Piedras Campus, University of Puerto Rico, San Juan (Puerto Rico); Center for Environmental and Toxicological Research, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan (Puerto Rico); Gioda, Adriana [Department of Biochemistry, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan (Puerto Rico); Center for Environmental and Toxicological Research, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan (Puerto Rico); Department of Chemistry, Pontifical Catholic University of Rio de Janeiro (PUC-Rio), Marques de Sao Vicente street, 225, Gavea, 22453-900, Rio de Janeiro (Brazil); Sanchez-Rivera, Diana; Roman-Velazquez, Felix R. [Department of Chemistry, Mayaguez Campus, University of Puerto Rico, Mayaguez (Puerto Rico); Jimenez-Velez, Braulio D., E-mail: braulio.jimenez@upr.ed [Department of Biochemistry, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan (Puerto Rico); Center for Environmental and Toxicological Research, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan (Puerto Rico)

    2010-03-15T23:59:59.000Z

    Fine particulate air pollutants, mainly their organic fraction, have been demonstrated to be associated with cardiovascular and respiratory health problems. Puerto Rico has been reported to have the highest prevalence of pulmonary diseases (e.g., asthma) in the United States. The aim of this study was to assess, for the first time, the immunological response of human bronchial epithelial cells (BEAS-2B) to organic extracts isolated from airborne particulate matter (PM{sub 2.5}) in Puerto Rico. Organic extracts from PM{sub 2.5} collected throughout an 8-month period (2000-2001) were pooled (composite) in order to perform chemical analysis and biological activity testing. BEAS-2B cells were exposed to PM{sub 2.5} organic extract to assess cytotoxicity, levels of cytokines and relative gene expression of MHC-II, hPXR and CYP3A5. Our findings show that organic PM{sub 2.5} consist of toxic as well as bioactive components that can regulate the secretion of cytokines in BEAS-2B, which could modulate inflammatory response in the lung. Trace element analyses confirmed the presence of metals in organic extracts highlighting the relative high abundance of Cu and Zn in polar organic extracts. Polar organic extracts exhibited dose-dependant toxicity and were found to significantly induce the release of interleukin 6 (IL-6), IL-1beta and IL-7 while significantly inhibiting the secretion of IL-8, G-CSF and MCP-1. Moreover, MHC-II transcriptional activity was up-regulated after 24 h of exposure, whereas PXR and CYP3A5 were down-regulated. This research provides a new insight into the effects of PM{sub 2.5} organic fractions on specific effectors and their possible role in the development of respiratory inflammatory diseases in Puerto Rico.

  7. Liver X receptor alpha mediated genistein induction of human dehydroepiandrosterone sulfotransferase (hSULT2A1) in Hep G2 cells

    SciTech Connect (OSTI)

    Chen, Yue; Zhang, Shunfen [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078 (United States); Zhou, Tianyan [Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100083 (China); Huang, Chaoqun; McLaughlin, Alicia [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078 (United States); Chen, Guangping, E-mail: guangping.chen@okstate.edu [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078 (United States)

    2013-04-15T23:59:59.000Z

    Cytosolic sulfotransferases are one of the major families of phase II drug metabolizing enzymes. Sulfotransferase-catalyzed sulfonation regulates hormone activities, metabolizes drugs, detoxifies xenobiotics, and bioactivates carcinogens. Human dehydroepiandrosterone sulfotransferase (hSULT2A1) plays important biological roles by sulfating endogenous hydroxysteroids and exogenous xenobiotics. Genistein, mainly existing in soy food products, is a naturally occurring phytoestrogen with both chemopreventive and chemotherapeutic potential. Our previous studies have shown that genistein significantly induces hSULT2A1 in Hep G2 and Caco-2 cells. In this study, we investigated the roles of liver X receptor (LXR?) in the genistein induction of hSULT2A1. LXRs have been shown to induce expression of mouse Sult2a9 and hSULT2A1 gene. Our results demonstrate that LXR? mediates the genistein induction of hSULT2A1, supported by Western blot analysis results, hSULT2A1 promoter driven luciferase reporter gene assay results, and mRNA interference results. Chromatin immunoprecipitation (ChIP) assay results demonstrate that genistein increase the recruitment of hLXR? binding to the hSULT2A1 promoter. These results suggest that hLXR? plays an important role in the hSULT2A1 gene regulation. The biological functions of phytoestrogens may partially relate to their induction activity toward hydroxysteroid SULT. - Highlights: ? Liver X receptor ? mediated genistein induction of hSULT2A1 in Hep G2 cells. ? LXR? and RXR? dimerization further activated this induction. ? Western blot results agreed well with luciferase reporter gene assay results. ? LXRs gene silencing significantly decreased hSULT2A1 expression. ? ChIP analysis suggested that genistein enhances hLXR? binding to the hSULT2A1 promoter.

  8. OSU-A9 inhibits angiogenesis in human umbilical vein endothelial cells via disrupting Akt–NF-?B and MAPK signaling pathways

    SciTech Connect (OSTI)

    Omar, Hany A. [Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210 (United States); Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514 (Egypt); Arafa, El-Shaimaa A. [Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514 (Egypt); Salama, Samir A. [Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11511 (Egypt); Arab, Hany H. [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt); Wu, Chieh-Hsi, E-mail: chhswu@mail.cmu.edu.tw [School of Pharmacy, China Medical University, Taichung 40402, Taiwan (China); Weng, Jing-Ru, E-mail: columnster@gmail.com [Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan (China)

    2013-11-01T23:59:59.000Z

    Since the introduction of angiogenesis as a useful target for cancer therapy, few agents have been approved for clinical use due to the rapid development of resistance. This problem can be minimized by simultaneous targeting of multiple angiogenesis signaling pathways, a potential strategy in cancer management known as polypharmacology. The current study aimed at exploring the anti-angiogenic activity of OSU-A9, an indole-3-carbinol-derived pleotropic agent that targets mainly Akt–nuclear factor-kappa B (NF-?B) signaling which regulates many key players of angiogenesis such as vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Human umbilical vein endothelial cells (HUVECs) were used to study the in vitro anti-angiogenic effect of OSU-A9 on several key steps of angiogenesis. Results showed that OSU-A9 effectively inhibited cell proliferation and induced apoptosis and cell cycle arrest in HUVECs. Besides, OSU-A9 inhibited angiogenesis as evidenced by abrogation of migration/invasion and Matrigel tube formation in HUVECs and attenuation of the in vivo neovascularization in the chicken chorioallantoic membrane assay. Mechanistically, Western blot, RT-PCR and ELISA analyses showed the ability of OSU-A9 to inhibit MMP-2 production and VEGF expression induced by hypoxia or phorbol-12-myristyl-13-acetate. Furthermore, dual inhibition of Akt–NF-?B and mitogen-activated protein kinase (MAPK) signaling, the key regulators of angiogenesis, was observed. Together, the current study highlights evidences for the promising anti-angiogenic activity of OSU-A9, at least in part through the inhibition of Akt–NF-?B and MAPK signaling and their consequent inhibition of VEGF and MMP-2. These findings support OSU-A9's clinical promise as a component of anticancer therapy. - Highlights: • The antiangiogenic activity of OSU-A9 in HUVECs was explored. • OSU-A9 inhibited HUVECs proliferation, migration, invasion and tube formation. • OSU-A9 targeted signaling pathways mediated by Akt-NF-kB, VEGF, and MMP-2. • The anti-angiogenic activity of OSU-A9 supports its clinical promise.

  9. In-situ measurement of skin friction and point bearing 

    E-Print Network [OSTI]

    Rehmet, Joseph Don

    1970-01-01T23:59:59.000Z

    I M ? S IT U ME~c S UBEME6'T OF SKIN FRICTION PHD POINT BEARIiiG A Thesis JOS'- P':i QOij' REAMS T Suhmitted to th Gradua. e Colloa of Texas ASM Univer "it@ ln oar i! al f ul fl11ment of the requi ri ment for tha ~loc ~ ec of NP STE!3...-Situ Measurement of Skin Friction and Point Bearing (January 1970) Joseph D . Rehmet, B. S . , Texas A&M University Supervised by: Dr. Harry M. Coyle Field tests are made using several in-situ testing devices and limiting values of skin friction and point...

  10. Effects of Low-Dose Alpha-Particle Irradiation in Human Cells: The Role of Induced Genes and the Bystander Effect. Final Technical Report (9/15/1998-5/31/2005)

    SciTech Connect (OSTI)

    Little, John B.

    2013-09-17T23:59:59.000Z

    This grant was designed to examine the cellular and molecular mechanisms for the bystander effect of radiation (initially described in this laboratory) whereby damage signals are passed from irradiated to non-irradiated cells in a population. These signals induce genetic effects including DNA damage, mutations and chromosomal aberrations in the nonirradiated cells. Experiments were carried out in cultured mammalian cells, primarily human diploid cells, irradiated with alpha particles. This research resulted in 17 publications in the refereed literature and is described in the Progress Report where it is keyed to the publication list. This project was initiated at the Harvard School of Public Health (HSPH) and continued in collaboration with students/fellows at Colorado State University (CSU) and the New Jersey Medical School (NJMS).

  11. Mpemba paradox: Hydrogen bond memory and water-skin supersolidity

    E-Print Network [OSTI]

    Chang Q Sun

    2015-01-05T23:59:59.000Z

    Numerical reproduction of measurements, experimental evidence for skin super-solidity and hydrogen-bond memory clarified that Mpemba paradox integrates the heat emission-conduction-dissipation dynamics in the source-path-drain cycle system.

  12. Carmichael's Concise Review Microscopy is Only Skin Deep

    E-Print Network [OSTI]

    Heller, Eric

    Carmichael's Concise Review Microscopy is Only Skin Deep Stephen W. Carmichael Mayo Clinic. Coming Events 2011 EMAS 2011 May 15­19, 2011 Angers, France www.emas-web.net IUMAS-V May 22­27, 2011

  13. acute skin reaction: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    from a complex reaction induced by plant pigments exposed to ultraviolet (UV) wave length sunlight in the skin of animals that have eaten certain plants 1-3. This reaction is...

  14. artificial skin construct: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    with ultra-low density and high thermal stability. The supersolidity of skin sliperizes ice. Xi Zhang; Yongli Huang; a Zengsheng Ma; Yichun Zhou; Chang Q Sun 2013-10-03 66...

  15. attenuate skin dryness: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    with ultra-low density and high thermal stability. The supersolidity of skin sliperizes ice. Xi Zhang; Yongli Huang; a Zengsheng Ma; Yichun Zhou; Chang Q Sun 2013-10-03 9 Journal...

  16. artificial skin applications: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    with ultra-low density and high thermal stability. The supersolidity of skin sliperizes ice. Xi Zhang; Yongli Huang; a Zengsheng Ma; Yichun Zhou; Chang Q Sun 2013-10-03 117 An...

  17. allergic skin disease: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    of the microbiome...The Skin Microbiome in Healthy and Allergic Dogs Aline Rodrigues Hoffmann1*, Adam P. Patterson2, Alison Diesel2, Sara D. Lawhon4, Hoai Jaclyn Ly1, Christine...

  18. allergic skin diseases: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    of the microbiome...The Skin Microbiome in Healthy and Allergic Dogs Aline Rodrigues Hoffmann1*, Adam P. Patterson2, Alison Diesel2, Sara D. Lawhon4, Hoai Jaclyn Ly1, Christine...

  19. Involvement of TGF-beta in skin photoaging

    E-Print Network [OSTI]

    Choi, Won Seon, 1975-

    2005-01-01T23:59:59.000Z

    The goal of this thesis study was to understand the role of TGF-[beta] in skin photoaging, especially in solar elastosis. Solar elastosis, the accumulation of elastotic material in the dermal extracelluar matrix, is a major ...

  20. Double trisomy mosaic (47,XXX/48,XXX,+13) confirmed by FISH and skin fibroblast culture

    SciTech Connect (OSTI)

    Lieber, E.; Grady, V.; Dosik, H. [Interfaith Medical Center, Brooklyn, NY (United States)] [and others

    1994-09-01T23:59:59.000Z

    A 4 lb 8 oz female was born to a 49-year-old woman (P1200G12) at 40 weeks. The baby had tetralogy of Fallot, polydactyly, microcephaly, low set simple ears, posterior cleft of the soft palate and overlapping flexion deformities of both hands. The eyes were deep set. The clinical impression was trisomy 13. The baby is not doing well and needs a gastrotomy tube for feeding. Sucking is allright but swallowing is impeded. An MRI showed an anomaly of the corpus callosum. The ophthalmological examination showed no abnormalities. A chromosome study on a 2-day peripheral blood sample resulted in poor growth and poor morphology; however, 20 Giemsa-banded cells revealed a 47,XXX karyotype. A second specimen was obtained to search for mosaicism and a blood smear revealed nuclear projections on the neutrophils. FISH analysis using whole chromosome painting probe (Life Technologies) first identified the extra chromosome number 13, the final results showing five of sixty metaphase cells (8.3%) with trisomy 13. Cytogenetic analysis using Giemsa-banding technique revealed four cells in fifty examined (8.0%) with a 48,XXX,+13 karyotype. In order to further evaluate the mosaicism, cytogenetic analysis of a skin fibroblast culture was performed. Twenty one of twenty three cells examined (91.3%) showed the 48,XXX,+13 karyotype. FISH analysis of the skin biopsy revealed eighteen of twenty cells (90.9%) with the trisomy 13. The FISH technique is an important enhancement to routine cytogenetic studies when they do not immediately correlate with clinical impressions.

  1. Dynamic change of histone H2AX phosphorylation independent of ATM and DNA-PK in mouse skin in situ

    SciTech Connect (OSTI)

    Koike, Manabu [DNA Repair Gene Research, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)], E-mail: m_koike@nirs.go.jp; Mashino, Minako; Sugasawa, Jun; Koike, Aki [DNA Repair Gene Research, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2007-11-30T23:59:59.000Z

    Histone H2AX undergoes phosphorylation on Ser 139 ({gamma}-H2AX) rapidly in response to DNA double-strand breaks induced by exogenous stimuli, such as ionizing radiation. However, the endogenous phosphorylation pattern and modifier of H2AX remain unclear. Here we show that H2AX is regulated physically at the level of phosphorylation at Ser139 during a hair cycle in the mouse skin. In anagen hair follicles, {gamma}-H2AX-positive cells were observed in the outer root sheath (ORS) and hair bulb in a cycling inferior region but not in a permanent superficial region. In telogen hair follicles, {gamma}-H2AX-positive cells were only detected around the germ cell cap. In contrast, following X-irradiation, {gamma}-H2AX was observed in various cell types including the ORS cells in the permanent superficial region. Furthermore, {gamma}-H2AX-positive cells were detected in the skin of mice lacking either ATM or DNA-PK, suggesting that these kinases are not essential for phosphorylation in vivo.

  2. Temporal-spatial analysis of U.S.-Mexico border environmental fine and coarse PM air sample extract activity in human bronchial epithelial cells

    SciTech Connect (OSTI)

    Lauer, Fredine T.; Mitchell, Leah A. [University of New Mexico Center for Environmental Health Sciences, Albuquerque, NM (United States); College of Pharmacy, University of New Mexico, Albuquerque, NM (United States); Bedrick, Edward [University of New Mexico Center for Environmental Health Sciences, Albuquerque, NM (United States); School of Medicine, Dept. of Internal Medicine - Division of Epidemiology and Biostatistics, University of New Mexico, Albuquerque, NM (United States); McDonald, Jacob D. [University of New Mexico Center for Environmental Health Sciences, Albuquerque, NM (United States); Lovelace Respiratory Research Institute, Albuquerque, NM (United States); Lee, Wen-Yee [University of Texas at El Paso Center for Environmental Resource Management, El Paso, TX (United States); Department of Chemistry, University of Texas at El Paso, El Paso, TX (United States); Li, Wen-Whai; Olvera, Hector [University of Texas at El Paso Center for Environmental Resource Management, El Paso, TX (United States); Department of Civil Engineering, University of Texas at El Paso, El Paso, TX (United States); Amaya, Maria A. [University of Texas at El Paso Center for Environmental Resource Management, El Paso, TX (United States); School of Nursing, University of Texas at El Paso, El Paso, TX (United States); Berwick, Marianne; Gonzales, Melissa [University of New Mexico Center for Environmental Health Sciences, Albuquerque, NM (United States); School of Medicine, Dept. of Internal Medicine - Division of Epidemiology and Biostatistics, University of New Mexico, Albuquerque, NM (United States); Currey, Robert [University of Texas at El Paso Center for Environmental Resource Management, El Paso, TX (United States); Pingitore, Nicholas E. [University of Texas at El Paso Center for Environmental Resource Management, El Paso, TX (United States); Department of Geological Sciences, University of Texas at El Paso, El Paso, TX (United States)] (and others)

    2009-07-01T23:59:59.000Z

    Particulate matter less than 10 {mu}m (PM10) has been shown to be associated with aggravation of asthma and respiratory and cardiopulmonary morbidity. There is also great interest in the potential health effects of PM2.5. Particulate matter (PM) varies in composition both spatially and temporally depending on the source, location and seasonal condition. El Paso County which lies in the Paso del Norte airshed is a unique location to study ambient air pollution due to three major points: the geological land formation, the relatively large population and the various sources of PM. In this study, dichotomous filters were collected from various sites in El Paso County every 7 days for a period of 1 year. The sampling sites were both distant and near border crossings, which are near heavily populated areas with high traffic volume. Fine (PM2.5) and Coarse (PM10-2.5) PM filter samples were extracted using dichloromethane and were assessed for biologic activity and polycyclic aromatic (PAH) content. Three sets of marker genes human BEAS2B bronchial epithelial cells were utilized to assess the effects of airborne PAHs on biologic activities associated with specific biological pathways associated with airway diseases. These pathways included in inflammatory cytokine production (IL-6, IL-8), oxidative stress (HMOX-1, NQO-1, ALDH3A1, AKR1C1), and aryl hydrocarbon receptor (AhR)-dependent signaling (CYP1A1). Results demonstrated interesting temporal and spatial patterns of gene induction for all pathways, particularly those associated with oxidative stress, and significant differences in the PAHs detected in the PM10-2.5 and PM2.5 fractions. Temporally, the greatest effects on gene induction were observed in winter months, which appeared to correlate with inversions that are common in the air basin. Spatially, the greatest gene expression increases were seen in extracts collected from the central most areas of El Paso which are also closest to highways and border crossings.

  3. Method of forming a continuous polymeric skin on a cellular foam material

    DOE Patents [OSTI]

    Duchane, David V. (Los Alamos, NM); Barthell, Barry L. (Los Alamos, NM)

    1985-01-01T23:59:59.000Z

    Hydrophobic cellular material is coated with a thin hydrophilic polymer skin which stretches tightly over the outer surface of the foam but which does not fill the cells of the foam, thus resulting in a polymer-coated foam structure having a smoothness which was not possible in the prior art. In particular, when the hydrophobic cellular material is a specially chosen hydrophobic polymer foam and is formed into arbitrarily chosen shapes prior to the coating with hydrophilic polymer, inertial confinement fusion (ICF) targets of arbitrary shapes can be produced by subsequently coating the shapes with metal or with any other suitable material. New articles of manufacture are produced, including improved ICF targets, improved integrated circuits, and improved solar reflectors and solar collectors. In the coating method, the cell size of the hydrophobic cellular material, the viscosity of the polymer solution used to coat, and the surface tensin of the polymer solution used to coat are all very important to the coating.

  4. How do microbial fuel cells (MFCs) work? Bacteria need energy to survive, in the same way that humans need food to

    E-Print Network [OSTI]

    Lee, Dongwon

    How do microbial fuel cells (MFCs) work? Bacteria need energy to survive, in the same way" in photobiological fuel cell systems that utilize photosynthetic bacteria, amino acids, and proteins. What

  5. RhoE interferes with Rb inactivation and regulates the proliferation and survival of the U87 human glioblastoma cell line

    SciTech Connect (OSTI)

    Poch, Enric [Departamento de Quimica, Bioquimica y Biologia Molecular, Universidad Cardenal Herrera-CEU, Valencia (Spain); Minambres, Rebeca [Laboratorio de Patologia Celular, Centro de Investigacion Principe Felipe, Valencia (Spain); Mocholi, Enric [Departamento de Quimica, Bioquimica y Biologia Molecular, Universidad Cardenal Herrera-CEU, Valencia (Spain); Ivorra, Carmen [Departamento de Quimica, Bioquimica y Biologia Molecular, Universidad Cardenal Herrera-CEU, Valencia (Spain); Perez-Arago, Amparo [Laboratorio de Patologia Celular, Centro de Investigacion Principe Felipe, Valencia (Spain); Guerri, Consuelo [Laboratorio de Patologia Celular, Centro de Investigacion Principe Felipe, Valencia (Spain); Perez-Roger, Ignacio [Departamento de Quimica, Bioquimica y Biologia Molecular, Universidad Cardenal Herrera-CEU, Valencia (Spain)]. E-mail: iperez@uch.ceu.es; Guasch, Rosa M. [Laboratorio de Patologia Celular, Centro de Investigacion Principe Felipe, Valencia (Spain)]. E-mail: guasch@cipf.es

    2007-02-15T23:59:59.000Z

    Rho GTPases are important regulators of actin cytoskeleton, but they are also involved in cell proliferation, transformation and oncogenesis. One of this proteins, RhoE, inhibits cell proliferation, however the mechanism that regulates this effect remains poorly understood. Therefore, we undertook the present study to determine the role of RhoE in the regulation of cell proliferation. For this purpose we generated an adenovirus system to overexpress RhoE in U87 glioblastoma cells. Our results show that RhoE disrupts actin cytoskeleton organization and inhibits U87 glioblastoma cell proliferation. Importantly, RhoE expressing cells show a reduction in Rb phosphorylation and in cyclin D1 expression. Furthermore, RhoE inhibits ERK activation following serum stimulation of quiescent cells. Based in these findings, we propose that RhoE inhibits ERK activation, thereby decreasing cyclin D1 expression and leading to a reduction in Rb inactivation, and that this mechanism is involved in the RhoE-induced cell growth inhibition. Moreover, we also demonstrate that RhoE induces apoptosis in U87 cells and also in colon carcinoma and melanoma cells. These results indicate that RhoE plays an important role in the regulation of cell proliferation and survival, and suggest that this protein may be considered as an oncosupressor since it is capable to induce apoptosis in several tumor cell lines.

  6. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Progress report, July 1992--August 1993

    SciTech Connect (OSTI)

    Rowley, J.D.

    1993-09-01T23:59:59.000Z

    Progress in identification of chromosomal transformations associated with leukemogenesis is described. In particular progress in DNA cloning of chromosomal break points in human cancer patients is described.

  7. A Supersolid Skin Covering both Water and Ice

    E-Print Network [OSTI]

    Sun, Chang Q

    2014-01-01T23:59:59.000Z

    The mysterious nature and functionality of water and ice skins remain baffling to the community since 1859 when Farady firstly proposed liquid skin lubricating ice. Here we show the presence of supersolid phase that covers both water and ice using Raman spectroscopy measurements and quantum calculations. In the skin of two molecular layers thick, molecular undercoordination shortens the H-O bond by ~16% and lengthens the OH nonbond by ~25% through repulsion between electron pairs on adjacent O atoms, which depresses the density from 0.92 for bulk ice to 0.75 gcm-3. The O:H-O cooperative relaxation stiffens the H-O stretching phonon from 3200/3150 cm-1 to the same value of 3450 cm-1 and raises the melting temperature of both skins by up to ~310 K. Numerical derivatives on the viscosity and charge accumulation suggests that the elastic, polarized, and thermally stable supersolid phase makes the ice frictionless and water skin hydrophobic and ice like at room temperature.

  8. Antiproliferative effects of phenylaminonaphthoquinones are increased by ascorbate and associated with the appearance of a senescent phenotype in human bladder cancer cells

    SciTech Connect (OSTI)

    Felipe, K.B. [Laboratorio de Bioquímica Experimental, Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis (Brazil)] [Laboratorio de Bioquímica Experimental, Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis (Brazil); Benites, J. [Facultad de Ciencias de la Salud, Universidad Arturo Prat, Avenida Arturo Prat 2120, Casilla 121, Iquique (Chile)] [Facultad de Ciencias de la Salud, Universidad Arturo Prat, Avenida Arturo Prat 2120, Casilla 121, Iquique (Chile); Glorieux, C.; Sid, B.; Valenzuela, M. [Université Catholique de Louvain, Louvain Drug Research Institute, Toxicology and Cancer Biology Research Group (GTOX), Brussels (Belgium)] [Université Catholique de Louvain, Louvain Drug Research Institute, Toxicology and Cancer Biology Research Group (GTOX), Brussels (Belgium); Kviecinski, M.R.; Pedrosa, R.C. [Laboratorio de Bioquímica Experimental, Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis (Brazil)] [Laboratorio de Bioquímica Experimental, Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis (Brazil); Valderrama, J.A. [Departamento Química Orgánica, Pontificia Universidad Católica de Chile, Vicuña Mackenna 4860, Casilla 306, Santiago (Chile)] [Departamento Química Orgánica, Pontificia Universidad Católica de Chile, Vicuña Mackenna 4860, Casilla 306, Santiago (Chile); Levêque, Ph.; Gallez, B. [Université Catholique de Louvain, Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group (REMA), Brussels (Belgium)] [Université Catholique de Louvain, Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group (REMA), Brussels (Belgium); Verrax, J. [Université Catholique de Louvain, Louvain Drug Research Institute, Toxicology and Cancer Biology Research Group (GTOX), Brussels (Belgium)] [Université Catholique de Louvain, Louvain Drug Research Institute, Toxicology and Cancer Biology Research Group (GTOX), Brussels (Belgium); Buc Calderon, P., E-mail: pedro.buccalderon@uclouvain.be [Facultad de Ciencias de la Salud, Universidad Arturo Prat, Avenida Arturo Prat 2120, Casilla 121, Iquique (Chile); Université Catholique de Louvain, Louvain Drug Research Institute, Toxicology and Cancer Biology Research Group (GTOX), Brussels (Belgium)

    2013-04-19T23:59:59.000Z

    Highlights: •Phenylaminonaphthoquinones are redox cyclers able to form ROS. •Phenylaminonaphthoquinones plus ascorbate inhibit T24 cell growth. •Phenylaminonaphthoquinones plus ascorbate lead to necrotic-like cell death. •Phenylaminonaphthoquinones plus ascorbate impair cell cycle and affect MAPKs. •Phenylaminonaphthoquinones plus ascorbate induce a senescent cancer cell phenotype. -- Abstract: Quinone-containing molecules have been developed against cancer mainly for their redox cycling ability leading to reactive oxygen species (ROS) formation. We have previously shown that donor-acceptor phenylaminonaphthoquinones are biologically active against a panel of cancer cells. In this report, we explored the mechanisms involved in cancer cell growth inhibition caused by two phenylaminonaphthoquinones, namely Q7 and Q9, with or without ascorbate (ASC). The results show that Q7 and Q9 are both redox cyclers able to form ROS, which strongly inhibit the proliferation of T24 cells. Q9 was a better redox cycler than Q7 because of marked stabilization of the semiquinone radical species arising from its reduction by ascorbate. Indeed, ASC dramatically enhances the inhibitory effect of Q9 on cell proliferation. Q9 plus ASC impairs the cell cycle, causing a decrease in the number of cells in the G2/M phase without involving other cell cycle regulating key proteins. Moreover, Q9 plus ASC influences the MAPK signaling pathways, provoking the appearance of a senescent cancer cell phenotype and ultimately leading to necrotic-like cell death. Because cellular senescence limits the replicative capacity of cells, our results suggest that induction of senescence may be exploited as a basis for new approaches to cancer therapy.

  9. 2-(3-Methoxyphenyl)-5-methyl-1,8-naphthyridin-4(1H)-one (HKL-1) induces G2/M arrest and mitotic catastrophe in human leukemia HL-60 cells

    SciTech Connect (OSTI)

    Hsu, Mei-Hua; Liu, Chin-Yu; Lin, Chiao-Min; Chen, Yen-Jung; Chen, Chun-Jen; Lin, Yu-Fu; Huang, Li-Jiau [Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan, ROC (China)] [Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan, ROC (China); Lee, Kuo-Hsiung [Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States) [Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan, ROC (China); Kuo, Sheng-Chu, E-mail: sckuo@mail.cmu.edu.tw [Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan, ROC (China)] [Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan, ROC (China)

    2012-03-01T23:59:59.000Z

    2-(3-Methoxyphenyl)-5-methyl-1,8-naphthyridin-4(1H)-one (HKL-1), a 2-phenyl-1,8-naphthyridin-4-one (2-PN) derivative, was synthesized and evaluated as an effective antimitotic agent in our laboratory. However, the molecular mechanisms are uncertain. In this study, HKL-1 was demonstrated to induce multipolar spindles, sustain mitotic arrest and generate multinucleated cells, all of which indicate mitotic catastrophe, in human leukemia HL-60 cells. Western blotting showed that HKL-1 induces mitotic catastrophe in HL-60 cells through regulating mitotic phase-specific kinases (down-regulating CDK1, cyclin B1, CENP-E, and aurora B) and regulating the expression of Bcl-2 family proteins (down-regulating Bcl-2 and up-regulating Bax and Bak), followed by caspase-9/-3 cleavage. These findings suggest that HKL-1 appears to exert its cytotoxicity toward HL-60 cells in culture by inducing mitotic catastrophe. Highlights: ? HKL-1 is a potential antimitotic agent against HL-60 cells. ? HKL-1 induces spindle disruption and sustained resulted in mitotic catastrophe. ? CENP-E and aurora B protein expressions significantly reduced. ? Bcl-2 family protein expressions altered and caspase-9/-3 activation. ? HKL-1 is an attractive candidate for possible use as a novel antimitotic agent.

  10. The PIKfyve–ArPIKfyve–Sac3 triad in human breast cancer: Functional link between elevated Sac3 phosphatase and enhanced proliferation of triple negative cell lines

    SciTech Connect (OSTI)

    Ikonomov, Ognian C., E-mail: oikonomo@med.wayne.edu; Filios, Catherine, E-mail: cfilios@med.wayne.edu; Sbrissa, Diego, E-mail: dsbrissa@med.wayne.edu; Chen, Xuequn, E-mail: xchen@med.wayne.edu; Shisheva, Assia, E-mail: ashishev@med.wayne.edu

    2013-10-18T23:59:59.000Z

    Highlights: •We assess PAS complex proteins and phosphoinositide levels in breast cancer cells. •Sac3 and ArPIKfyve are markedly elevated in triple-negative breast cancer cells. •Sac3 silencing inhibits proliferation in triple-negative breast cancer cell lines. •Phosphoinositide profiles are altered in breast cancer cells. •This is the first evidence linking high Sac3 with breast cancer cell proliferation. -- Abstract: The phosphoinositide 5-kinase PIKfyve and 5-phosphatase Sac3 are scaffolded by ArPIKfyve in the PIKfyve–ArPIKfyve–Sac3 (PAS) regulatory complex to trigger a unique loop of PtdIns3P–PtdIns(3,5)P{sub 2} synthesis and turnover. Whereas the metabolizing enzymes of the other 3-phosphoinositides have already been implicated in breast cancer, the role of the PAS proteins and the PtdIns3P–PtdIns(3,5)P{sub 2} conversion is unknown. To begin elucidating their roles, in this study we monitored the endogenous levels of the PAS complex proteins in cell lines derived from hormone-receptor positive (MCF7 and T47D) or triple-negative breast cancers (TNBC) (BT20, BT549 and MDA-MB-231) as well as in MCF10A cells derived from non-tumorigenic mastectomy. We report profound upregulation of Sac3 and ArPIKfyve in the triple negative vs. hormone-sensitive breast cancer or non-tumorigenic cells, with BT cell lines showing the highest levels. siRNA-mediated knockdown of Sac3, but not that of PIKfyve, significantly inhibited proliferation of BT20 and BT549 cells. In these cells, knockdown of ArPIKfyve had only a minor effect, consistent with a primary role for Sac3 in TNBC cell proliferation. Intriguingly, steady-state levels of PtdIns(3,5)P{sub 2} in BT20 and T47D cells were similar despite the 6-fold difference in Sac3 levels between these cell lines. However, steady-state levels of PtdIns3P and PtdIns5P, both regulated by the PAS complex, were significantly reduced in BT20 vs. T47D or MCF10A cell lines, consistent with elevated Sac3 affecting directly or indirectly the homeostasis of these lipids in TNBC. Together, our results uncover an unexpected role for Sac3 phosphatase in TNBC cell proliferation. Database analyses, discussed herein, reinforce the involvement of Sac3 in breast cancer pathogenesis.

  11. Interference of silibinin with IGF-1R signalling pathways protects human epidermoid carcinoma A431 cells from UVB-induced apoptosis

    SciTech Connect (OSTI)

    Liu, Weiwei; Otkur, Wuxiyar; Li, Lingzhi; Wang, Qiong; He, Hao; Zang, Linghe; Hayashi, Toshihiko [China–Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China)] [China–Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China); Tashiro, Shin-ichi [Institute for Clinical and Biomedical Sciences, Kyoto 603-8072 (Japan)] [Institute for Clinical and Biomedical Sciences, Kyoto 603-8072 (Japan); Onodera, Satoshi [Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University, Tokyo 194-8543 (Japan)] [Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University, Tokyo 194-8543 (Japan); Xia, Mingyu [China–Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China)] [China–Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China); Ikejima, Takashi, E-mail: ikejimat@vip.sina.com [China–Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China)] [China–Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China)

    2013-03-08T23:59:59.000Z

    Highlights: ? Silibinin protects A431 cells from UVB irradiation-induced apoptosis. ? Up-regulation of the IGF-1R-JNK/ERK pathways by UVB induces cell apoptosis. ? Silibinin inhibits IGF-1R pathways to repress caspase-8-mediated apoptosis. -- Abstract: Ultraviolet B (UVB) from sunlight is a major cause of cutaneous lesion. Silibinin, a traditional hepatic protectant, elicits protective effects against UVB-induced cellular damage. In A431 cells, the insulin-like growth factor-1 receptor (IGF-1R) was markedly up-regulated by UVB irradiation. The activation of the IGF-1R signalling pathways contributed to apoptosis of the cells rather than rescuing the cells from death. Up-regulated IGF-1R stimulated downstream mitogen-activated protein kinases (MAPKs), such as c-Jun N-terminal kinases (JNK) and extracellular signal-regulated protein kinases 1/2 (ERK1/2). The subsequent activation of caspase-8 and caspase-3 led to apoptosis. The activation of IGF-1R signalling pathways is the cause of A431 cell death. The pharmacological inhibitors and the small interfering RNA (siRNA) targeting IGF-1R suppressed the downstream activation of JNK/ERK-caspases to help the survival of the UVB-irradiated A431 cells. Indeed, silibinin treatment suppressed the IGF-1R-JNK/ERK pathways and thus protected the cells from UVB-induced apoptosis.

  12. The use of polarized light for skin cancer detecton

    E-Print Network [OSTI]

    DeLaughter, Aimee Hill

    2002-01-01T23:59:59.000Z

    and subsequent biopsy of suspicious lesions. Many cancerous lesions are missed and many benign lesions are biopsied using these techniques. This process is painful and expensive. The proposed research is driven by the need for a non-invasive skin cancer...

  13. MOBILE PHONE USE AND TEMPORAL SKIN HEAT SENSATION

    E-Print Network [OSTI]

    Boyer, Edmond

    in the phone by the battery currents and running of the radiofrequency (RF) electronic circuits measured the temperature of the temporal skin due to GSM 1800 MHz MP radiated power (125 mW). We suppressed of the heat produced in the phone by the battery currents and running of the radiofrequency (RF) electronic

  14. In-situ measurement of skin friction and point bearing

    E-Print Network [OSTI]

    Rehmet, Joseph Don

    1970-01-01T23:59:59.000Z

    in order to produce a specified sensitivity. The Skin FricCion Device This device (See Fig. 2a) was iabr'cated of 2. 375 in O. D. si e. . l tubing and 2 standard drill rod coupl- ings we Lded Lo Che Cube, ma). c on one &=n&l, female on Lhe other. Th...

  15. Subclonal variation and skin russeting in potato, (Solanum tuberosum L.)

    E-Print Network [OSTI]

    Oehlke, Leslie Lashaun

    1997-01-01T23:59:59.000Z

    of subclonal selection for putative russet skin mutations of 'Century Russet' was conducted in Texas and Colorado to improve the russeting character in 'Century Russet'. RAPD analysis of a segregating F I family derived from a russet x white cross and of three...

  16. HandWave : design and manufacture of a wearable wireless skin conductance sensor and housing

    E-Print Network [OSTI]

    Strauss, Marc D

    2005-01-01T23:59:59.000Z

    This thesis report details the design and manufacture of HandWave, a wearable wireless Bluetooth skin conductance sensor, and dedicated housing. The HandWave collects Electrodermal Activity (EDA) data by measuring skin ...

  17. A Solar Re-Skin at FedEx Field | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    A Solar Re-Skin at FedEx Field A Solar Re-Skin at FedEx Field August 2, 2011 - 10:40am Addthis Ramamoorthy Ramesh Former Director, SunShot Initiative & Solar Energy Technologies...

  18. The oncogenic action of ionizing radiation on rat skin. Final progress report, May 1, 1990--April 30, 1992

    SciTech Connect (OSTI)

    Burns, F.J.; Garte, S.J.

    1992-12-31T23:59:59.000Z

    The multistage theory of carcinogenesis specifies that cells progress to cancer through a series of discrete, irreversible genetic alterations, but data on radiation-induced cancer incidence in rat skin suggests that an intermediate repairable alteration may occur. Data are presented on cancer induction in rat skin exposed to an electron beam (LET=0.34 keV/{mu}), a neon ion beam (LET=45) or an argon ion beam (LET=125). The rats were observed for tumors at least 78 weeks with squamous and basal cell carcinomas observed. The total cancer yield was fitted by the quadratic equation, and the equation parameters were estimated by linear regression for each type of radiation. Analysis of the DNA from the electron-induced carcinomas indicated that K-ras and/or c-myc oncogenes were activated. In situ hybridization indicated that the cancers contain subpopulations of cells with differing amounts of c-myc and H-ras amplification. The results are consistent with the idea that ionizing radiation produces stable, carcinogenically relevant lesions via 2 repairable events at low LET and via a non-repairable linked event pathway at high LET; either pathway may advance the cell by 1 stage. The proliferative response of rat epidermis following exposure to ionizing radiation was quantified by injection of {sup 14}C-thymidine. The return of these cells to S-phase a second time was detected by a second label ({sup 3}H). When the labeled cells were in G1-phase, the dorsal skin was irradiated with X-rays. All labeling indices were determined. The {sup 14}C labeling index was constant and unaffected by the radiation. The proportion of all cells entering S-phase averaged 3.5% at 18 hr and increased after 44, 52 and 75 hr to average levels of 11.8%, 5. 3%, and 6.6% at 0, 10 and 25 Gy respectively. The proportion of S-phase cells labeled with {sup 14}C increased after 42 hr and remained relatively constant thereafter.

  19. Exploring Novel Properties of Adenomatous Polyposis Coli: Msi1-Knockout Mice Display Alterations in APC and Intestinal Cell Homeostasis; Topoisomerase IIa Binds to Truncated APC in Human Colon Cancer Cells

    E-Print Network [OSTI]

    Ernlund, Amanda Weis

    2011-12-31T23:59:59.000Z

    regulation. Our lab showed an interaction between the central portion of the APC protein and topoisomerase II?, which led to G2 cell cycle arrest. However, whether truncated APC and topo II? interact in colon cancer cells remained unknown. Here I present data...

  20. ON THE INFLUENCE OF THE GEOMETRY ON SKIN EFFECT IN ELECTROMAGNETISM

    E-Print Network [OSTI]

    ON THE INFLUENCE OF THE GEOMETRY ON SKIN EFFECT IN ELECTROMAGNETISM GABRIEL CALOZ, MONIQUE DAUGE, MONIQUE DAUGE, ERWAN FAOU, VICTOR P´ERON suitable skin depth function is introduced on the interface ­ and here the sign of the curvature has a major influence, which means that the skin depth is larger

  1. The Effect of Surface Wave Propagation on Neural Responses to Vibration in Primate Glabrous Skin

    E-Print Network [OSTI]

    Elias, Damian Octavio

    The Effect of Surface Wave Propagation on Neural Responses to Vibration in Primate Glabrous Skin preserved as it travels across the skin. Our results suggest, then, that the propagation of surface waves of Surface Wave Propagation on Neural Responses to Vibration in Primate Glabrous Skin. PLoS ONE 7(2): e31203

  2. Skin tone of targets, lineup type, and confidence levels in cross-racial identification

    E-Print Network [OSTI]

    Williamson, Jessica Lynne

    2013-02-22T23:59:59.000Z

    The current experiment investigated facial recognition memory for own and other-race faces. Two variations (light-skin and dark-skin) were presented for the Black targets. The purpose of this experiment was to observe the effect of skin variations...

  3. Skin cancer is the most com-mon form of cancer in the United

    E-Print Network [OSTI]

    Skin cancer is the most com- mon form of cancer in the United States. Excessive and unprotected exposure to the sun's ultraviolet radiation (UV light) is the primary risk factor for skin cancer. Howev- er, skin cancer is one of the most preventable types of cancer! The damaging and cumulative effects

  4. Skin Cancer: A Young Person's Disease By Lauren Duffy (B.S. Communication, Journalism '14)

    E-Print Network [OSTI]

    Massachusetts at Amherst, University of

    Skin Cancer: A Young Person's Disease By Lauren Duffy (B.S. Communication, Journalism '14 is that this behavior is extremely unhealthy and risky for their bodies, specifically their skin. Skin cancer is the most common form of cancer found in young adults and second most common cancer found in adolescents

  5. Reusable Skinning Templates Using Cage-based Deformations Qian-Yi Zhou2

    E-Print Network [OSTI]

    Southern California, University of

    Reusable Skinning Templates Using Cage-based Deformations Tao Ju1 Qian-Yi Zhou2 Michiel van de- lows skinning solutions to be shared and reused, and they allow a user to quickly explore many possible template. Skinning templates can be shared by users because they are not represented in a model

  6. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro

    E-Print Network [OSTI]

    2009-01-01T23:59:59.000Z

    and resistant cells. pRb and cyclin D 1 were elevated andretinoblastoma (Rb) gene product pRb is mediated in early Gcyclin D 1 . This results in pRB inactiva- tion and release

  7. Meeting Report. Assessing Human Germ-Cell Mutagenesis in the Post-Genome Era: A Celebration of the Legacy of William Lawson (Bill) Russell

    E-Print Network [OSTI]

    2006-01-01T23:59:59.000Z

    and 20 years after Chernobyl. Boice JD Jr, Tawn EJ, Winther2006. Cancer risk among Chernobyl cleanup workers in EstoniaDNA Germ-Cell Mutagenesis in Chernobyl, Japanese, and Animal

  8. Defective Regulation of Autophagy upon Leucine Deprivation Reveals a Targetable Liability of Human Melanoma Cells In Vitro and In Vivo

    E-Print Network [OSTI]

    Sheen, Joon-Ho

    Autophagy is of increasing interest as a target for cancer therapy. We find that leucine deprivation causes the caspase-dependent apoptotic death of melanoma cells because it fails to appropriately activate autophagy. ...

  9. Human radiation studies: Remembering the early years: Oral history of cell biologist Don Francis Petersen, Ph.D., conducted November 29, 1994

    SciTech Connect (OSTI)

    NONE

    1995-08-01T23:59:59.000Z

    This report is a transcript of an interview of Dr. Don Francis Petersen by representatives of the US DOE Office of Human Radiation Experiments. Dr. Petersen was selected for this interview because of his long research career at Los Alamos and his knowledge of the Atomic Energy Commission`s biomedical program. Dr. Petersen did not personally conduct research on human subjects. After a brief biographical sketch Dr. Petersen discusses his remembrances of the early use of radionuclides as biological tracers, aspects of nuclear weapons testing in the 1940`s and 1950`s including fallout studies, the means by which research projects were approved, use of humans in the whole-body counter, and the Health Division Biomedical responsibilities.

  10. The site of action of PTHrP's proliferative inhibition in non-small cell lung carcinoma

    E-Print Network [OSTI]

    Vander Werff, Ryan Peter

    2010-01-01T23:59:59.000Z

    hormone-related protein in lung cancer cell survival, Chesttreat human non-small cell lung carcinoma through inhibitingthe Growth of Orthotopic Human Lung Tumors in Athymic Mice

  11. Modulation of HLA-G and HLA-E expression in human neuronal cells after rabies virus or herpes virus simplex type -1 infections

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    virus simplex type -1 infections Françoise Megret1 , Christophe Prehaud1 , Mireille Lafage1 , Philippe), HSV-1 (herpes simplex virus type 1), mAb monoclonal antibody, HCMV ( Human cytomegalovirus) #12 to virus and tumour immune escape. We recently described that the herpes simplex virus type 1 (HSV-1

  12. Probing of a human proteome microarray with a recombinant pathogen protein reveals a novel mechanism by which hookworms suppress B cell receptor signaling

    E-Print Network [OSTI]

    Tribolet, Leon; Cantacessi, Cinzia; Pickering, Darren; Navarro, Severine; Doolan, Denise; Trieu, Angela; Fei, Huang; Chao, Yang; Hofmann, Andreas; Gasser, Robin; Giacomin, Paul; Loukas, Alex

    2014-08-19T23:59:59.000Z

    % low-quality bases. The remaining reads were 183 splice-aligned to the human genome reference assembly GRCh37 (NCBI build 37.1) using TopHat, 184 which incorporates the Bowtie v0.11.3 algorithm [25]; subsequently, individual aligned read files 185...

  13. Impact of complex NOTCH1 mutations on survival in paediatric T-cell leukaemia

    E-Print Network [OSTI]

    2012-01-01T23:59:59.000Z

    pathways in T cell acute lymphoblastic leukemia. Cancer Cellimpact in T-cell acute lymphoblastic leukemia outcome. Leukin human T cell acute lymphoblastic leukemia. Science 2004,

  14. Autoradiographic localization of endothelin-1 binding sites in porcine skin

    SciTech Connect (OSTI)

    Zhao, Y.D.; Springall, D.R.; Wharton, J.; Polak, J.M. (Royal Postgraduate Medical School, London (England))

    1991-01-01T23:59:59.000Z

    Autoradiographic techniques and {sup 125}I-labeled endothelin-1 were used to study the distribution of endothelin-1 binding sites in porcine skin. Specific endothelin-1 binding sites were localized to blood vessels (capillaries, deep cutaneous vascular plexus, arteries, and arterioles), the deep dermal and connective tissue sheath of hair follicles, sebaceous and sweat glands, and arrector pili muscle. Specific binding was inhibited by endothelin-2 and endothelin-3 as well as endothelin-1. Non-specific binding was found in the epidermis and the medulla of hair follicles. No binding was found in connective tissue or fat. These vascular binding sites may represent endothelin receptors, in keeping with the known cutaneous vasoconstrictor actions of the peptide. If all binding sites are receptors, the results suggest that endothelin could also regulate the function of sweat glands and may have trophic effects in the skin.

  15. Lithium Ion Battery Performance of Silicon Nanowires With Carbon Skin

    SciTech Connect (OSTI)

    Bogart, Timothy D.; Oka, Daichi; Lu, Xiaotang; Gu, Meng; Wang, Chong M.; Korgel, Brian A.

    2013-12-06T23:59:59.000Z

    Silicon (Si) nanomaterials have emerged as a leading candidate for next generation lithium-ion battery anodes. However, the low electrical conductivity of Si requires the use of conductive additives in the anode film. Here we report a solution-based synthesis of Si nanowires with a conductive carbon skin. Without any conductive additive, the Si nanowire electrodes exhibited capacities of over 2000 mA h g-1 for 100 cycles when cycled at C/10 and over 1200 mA h g-1 when cycled more rapidly at 1C against Li metal.. In situ transmission electron microscopy (TEM) observation reveals that the carbon skin performs dual roles: it speeds lithiation of the Si nanowires significantly, while also constraining the final volume expansion. The present work sheds light on ways to optimize lithium battery performance by smartly tailoring the nanostructure of composition of materials based on silicon and carbon.

  16. Anomalous skin effects in a weakly magnetized degenerate electron plasma

    SciTech Connect (OSTI)

    Abbas, G., E-mail: gohar.abbas@gcu.edu.pk; Sarfraz, M. [Department of Physics, GC University Lahore, Katchery Road, Lahore 54000 (Pakistan); Shah, H. A. [Forman Christian College University, Farozpur Road, Lahore 54600 (Pakistan)

    2014-09-15T23:59:59.000Z

    Fully relativistic analysis of anomalous skin effects for parallel propagating waves in a weakly magnetized degenerate electron plasma is presented and a graphical comparison is made with the results obtained using relativistic Maxwellian distribution function [G. Abbas, M. F. Bashir, and G. Murtaza, Phys. Plasmas 18, 102115 (2011)]. It is found that the penetration depth for R- and L-waves for degenerate case is qualitatively small in comparison with the Maxwellian plasma case. The quantitative reduction due to weak magnetic field in the skin depth in R-wave for degenerate plasma is large as compared to the non-degenerate one. By ignoring the ambient magnetic field, previous results for degenerate field free case are salvaged [A. F. Alexandrov, A. S. Bogdankevich, and A. A. Rukhadze, Principles of Plasma Electrodynamics (Springer-Verlag, Berlin/Heidelberg, 1984), p. 90].

  17. Skin effect with arbitrary specularity in Maxwellian plasma

    E-Print Network [OSTI]

    Anatoly V. Latyshev; Alexander A. Yushkanov

    2009-12-10T23:59:59.000Z

    The problem of skin effect with arbitrary specularity in maxwellian plasma with specular--diffuse boundary conditions is solved. A new analytical method is developed that makes it possible to to obtain a solution up to an arbitrary degree of accuracy. The method is based on the idea of symmetric continuation not only the electric field, but also electron distribution function. The solution is obtained in a form of von Neumann series.

  18. Intercellular Adhesion Molecule-1 Guides Naive T Cell Differentiation and Regulatory T Cell Induction

    E-Print Network [OSTI]

    Williams, Kelli M.

    2012-12-31T23:59:59.000Z

    ). Refer to Protocol 1 in the Appendix for more detail. In selected experiments where indicated, naïve CD4+ T cells were isolated from human tonsil tissue. In summary, tonsils were minced over a strainer to obtain cell suspensions, mononuclear cells...

  19. DU145 human prostate cancer cells express functional Receptor Activator of NF-B: New insights in the prostate cancer bone metastasis process.

    E-Print Network [OSTI]

    Boyer, Edmond

    in the prostate cancer bone metastasis process. Mori K.1, 2, * , Le Goff B. 1, 2 , Charrier C. 1, 2 , Battaglia S cells, thus facilitating prostate cancer metastasis development in bone. We confirm that RANKL is a factor that facilitates metastasis to bone by acting as an activator of both osteoclasts and RANK

  20. Metabolic Effects by Imatinib on Human Leukemia Cells S.Gottschalk, T.Dansauer, J.Miljus, D.Leibfritz, N.Serkova

    E-Print Network [OSTI]

    the energy metabolism was elevated after treatment, gleevec, unlike standard chemotherapeutics, stimulates after gleevec treatment by MRS, 5 mmol/l [1-13C] labeled glucose was added to the cells for the last 4 after gleevec incubation. Addition of gleevec strongly suppressed lactate production from [1-13C

  1. The Production and Analysis of Biodiesel from Waste Chicken Skin and Pork Skin Fat and a Comparison of Fuel Properties to Petroleum Derived Diesel Fuel

    E-Print Network [OSTI]

    Krish T Bharat; Agni Bhattacharya

    Abstract—People today are increasingly health conscious and therefore shopkeepers tend to dispose of fatty chicken and pork skin. Chicken and pork skins thus are sources of solid waste that are usually not utilized. This paper deals with the production of useful biodiesel from utilizing the waste chicken and pork skins. Fat from the waste chicken and pork skins (sourced from local shops), was first extracted and subjected to transesterification. The products of transesterification were FAME (Fatty acid methyl esters) and glycerol. The FAME produced was tested for five parameters namely calorific value, pour point and cloud point when compared to ASTM E2515-11 standard values. Comparison of the obtained values of the five parameters with the standard values for diesel was performed to determine the viability of the biodiesel produced. The results of this experiment showed that the calorific values of FAME produced from chicken skin and pork skin fat were close to that of petroleum derived diesel. However, two test parameters namely kinematic viscosity and pour point differed when compared to diesel; this problem can be circumvented by modifying an automobile’s internal combustion engine. Due to the relatively high yield value of biodiesel, it is feasible to utilize chicken skin and pork skin fat at a rural level to produce FAME that can be an alternative to diesel in this time of acute fuel scarcity.

  2. Human MSH2 protein

    DOE Patents [OSTI]

    de la Chapelle, Albert (Helsingfors, FI); Vogelstein, Bert (Baltimore, MD); Kinzler, Kenneth W. (Baltimore, MD)

    1997-01-01T23:59:59.000Z

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error.sup.+ (RER.sup.+) tumor cells.

  3. Human MSH2 protein

    DOE Patents [OSTI]

    Chapelle, A. de la; Vogelstein, B.; Kinzler, K.W.

    1997-01-07T23:59:59.000Z

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error{sup +} (RER{sup +}) tumor cells. 19 figs.

  4. THERMAL INTERACTION OF CRYOGEN SPRAY WITH HUMAN SKIN UNDER VACUUM PRESSURES

    E-Print Network [OSTI]

    Aguilar, Guillermo

    During the treatment of port wine stain (PWS) birthmarks laser energy is irradiated at appropriate Riverside, Riverside, CA, 92521, USA. gaguilar@engr.ucr.edu Abstract. Clinical results of port wine stain of this procedure is that laser energy is also absorbed by epidermal melanin, causing localized heating therein

  5. The eukaryotic translation elongation factor eEF1A2 induces neoplastic properties and mediates tumorigenic effects of ZNF217 in precursor cells of human ovarian carcinomas

    SciTech Connect (OSTI)

    Sun, Yu; Wong, Nicholas; Guan, Yinghui; Salamanca, Clara M.; Cheng, Jung Chien; Lee, Jonathan M.; Gray, Joe W.; Auersperg, Nelly

    2008-04-25T23:59:59.000Z

    Ovarian epithelial carcinomas (OEC) frequently exhibit amplifications at the 20q13 locus which is the site of several oncogenes, including the eukaryotic elongation factor EEF1A2 and the transcription factor ZNF217. We reported previously that overexpressed ZNF217 induces neoplastic characteristics in precursor cells of OEC. Unexpectedly, ZNF217, which is a transcriptional repressor, enhanced expression of eEF1A2. In this study, array comparative genomic hybridization, single nucleotide polymorphism and Affymetrix analysis of ZNF217-overexpressing cell lines confirmed consistently increased expression of eEF1A2 but not of other oncogenes, and revealed early changes in EEF1A2 gene copy numbers and increased expression at crisis during immortalization. We defined the influence of eEF1A2 overexpression on immortalized ovarian surface epithelial cells, and investigated interrelationships between effects of ZNF217 and eEF1A2 on cellular phenotypes. Lentivirally induced eEF1A2 overexpression caused delayed crisis, apoptosis resistance and increases in serum-independence, saturation densities, and anchorage independence. siRNA to eEF1A2 reversed apoptosis resistance and reduced anchorage independence in eEF1A2-overexpressing lines. Remarkably, siRNA to eEF1A2 was equally efficient in inhibiting both anchorage independence and resistance to apoptosis conferred by ZNF217 overexpression. Our data define neoplastic properties that are caused by eEF1A2 in nontumorigenic ovarian cancer precursor cells, and suggest that eEF1A2 plays a role in mediating ZNF217-induced neoplastic progression.

  6. Systematics of nucleon density distributions and neutron skin of nuclei

    E-Print Network [OSTI]

    Seif, W M

    2015-01-01T23:59:59.000Z

    Proton and neutron density profiles of 760 nuclei in the mass region of A=16-304are analyzed using the Skyrme energy density for the parameter set SLy4. Simple formulae are obtained to fit the resulting radii and diffuseness data. These formulae may be useful to estimate the values of the unmeasured radii, and especially in extrapolating charge radius values for nuclei which are far from the valley of stability or to perform analytic calculations for bound and/or scattering problems. The obtained neutron and proton root-mean-square radii and the neutron skin thicknesses are in agreement with the available experimental data.

  7. Induction of cytochromes P450 1A1 and 1A2 by tanshinones in human HepG2 hepatoma cell line

    SciTech Connect (OSTI)

    Zhang Rong [Key Laboratory of Drug Metabolism and Pharmacokinetics, Key Unit of SATCM for Pharmacokinetics Methodology of TCM Complex Prescription, China Pharmaceutical University, Nanjing (China); Sun Jianguo, E-mail: jgsun_cpucn@yahoo.com.cn [Key Laboratory of Drug Metabolism and Pharmacokinetics, Key Unit of SATCM for Pharmacokinetics Methodology of TCM Complex Prescription, China Pharmaceutical University, Nanjing (China); Ma Liping; Wu Xiaolan [Key Laboratory of Drug Metabolism and Pharmacokinetics, Key Unit of SATCM for Pharmacokinetics Methodology of TCM Complex Prescription, China Pharmaceutical University, Nanjing (China); Pan Guoyu [Metabolism and Pharmacokinetics (MAP), Novartis Institute of Biomedical Research (NIBR), 250 Massachusetts Avenue, Cambridge, Massachusetts (United States); Hao Haiping; Zhou Fang; Jiye, A; Liu Changhui; Ai Hua; Shang Lili; Gao Haiyan; Peng Ying; Wan Ping; Wu Hui [Key Laboratory of Drug Metabolism and Pharmacokinetics, Key Unit of SATCM for Pharmacokinetics Methodology of TCM Complex Prescription, China Pharmaceutical University, Nanjing (China); Wang Guangji, E-mail: guangjiwang@hotmail.com [Key Laboratory of Drug Metabolism and Pharmacokinetics, Key Unit of SATCM for Pharmacokinetics Methodology of TCM Complex Prescription, China Pharmaceutical University, Nanjing (China)

    2011-04-01T23:59:59.000Z

    Diterpenoid tanshinones including tanshinone IIA (TIIA), cryptotanshinone (CTS), tanshinone I (TI) and dihydrotanshinone I (DHTI) are the major bioactive components from Danshen. The major aim of our present study was to investigate the induction potential of these four main components of tanshinones (TIIA, CTS, TI, and DHTI) on the expression of CYP1A1 and CYP1A2 in HepG2 cells. Our results showed that all of these four tanshinones caused a significant time- and concentration-dependent increase in the amount of CYP1A1/2 expression in HepG2 cells. These induction effects were further characterized through transcriptional regulation: the induction of CYP1A1/2 mRNA level by tanshinones was completely blocked by the transcription inhibitor actinomycin D; the expression of CYP1A1/2 heterogeneous nuclear RNA was induced by tanshinone treatment; and CYP1A1 mRNA stability was not influenced by these tanshinones. Interestingly, tanshinones plus B[a]P produced additive/synergistic effect on CYP1A1/2 induction. In addition, the tanshinone-induced CYP1A1/2 expression was abolished by the aryl hydrocarbon receptor (AhR) antagonist resveratrol, suggesting an AhR dependent transcription mechanism. In the reporter gene assay, while TI and DHTI significantly induced AhR-dependent luciferase activity, TIIA and CTS failed to induce this activity. Collectively, the tanshinones could induce CYP1A1 and CYP1A2 expression through transcriptional activation mechanism and exert differential effects on activating AhR in HepG2 cells. Our findings suggest that rational administration of tanshinones should be considered with respect to their effect on AhR and CYP1A1/2 expression.

  8. Heritable Genetic Changes in Cells Recovered From Irradiated 3D Tissue Contracts. Final report

    SciTech Connect (OSTI)

    Cornforth, Michael N. [The University of Texas Medical Branch at Galveston, TX (United States)

    2013-05-03T23:59:59.000Z

    Combining contemporary cytogenetic methods with DNA CGH microarray technology and chromosome flow-sorting increases substantially the ability to resolve exchange breakpoints associated with interstitial deletions and translocations, allowing the consequences of radiation damage to be directly measured at low doses, while also providing valuable insights into molecular mechanisms of misrepair processes that, in turn, identify appropriate biophysical models of risk at low doses. The aims of this work apply to cells recovered from 3D tissue constructs of human skin and, for the purpose of comparison, the same cells irradiated in traditional 2D cultures. These aims are: to analyze by multi-flour fluorescence in situ hybridization (mFISH) the chromosomes in clonal descendents of individual human fibroblasts that were previously irradiated; to examine irradiated clones from Aim 1 for submicroscopic deletions by subjecting their DNA to comparative genomic hybridization (CGH) microarray analysis; and to flow-sort aberrant chromosomes from clones containing stable radiation-induced translocations and map the breakpoints to within an average resolution of 100 kb using the technique of 'array painting'.

  9. Management of Pediatric Skin Abscesses in Pediatric, General Academic and Community Emergency Departments

    E-Print Network [OSTI]

    2011-01-01T23:59:59.000Z

    Staphylococcus aureus (CA-MRSA) in skin abscesses presentingmeeting on management of MRSA in Conflicts of Interest: Byfor clinical management of MRSA in the community: Summary of

  10. Mechanisms of NDV-3 vaccine efficacy in MRSA skin versus invasive infection

    E-Print Network [OSTI]

    2014-01-01T23:59:59.000Z

    3 vaccine efficacy in MRSA skin versus invasive infectionFig. 1) and suppression of MRSA proliferation (Fig. 2). Eachseverity and suppression of MRSA bioluminescence (Figs. 1

  11. Recombination Breakpoints in the Human -Globin Gene Cluster By Rachelle A. Smith, P. Joy Ho, John B. Clegg, Judith R. Kidd, and Swee Lay Thein

    E-Print Network [OSTI]

    Kidd, Kenneth

    studied of all human loci; mutations here cause -thalassemia and sickle cell anemia, which are among

  12. Transcriptional functions of the corepressor Sin3A in skin

    E-Print Network [OSTI]

    Cox, Claire

    2013-03-12T23:59:59.000Z

    Upon activation in epidermal stem cells, the proto-oncogene c-Myc triggers their exit from the stem cell compartment resulting in an increase in progenitor cell proliferation and an induction in terminal differentiation. Whether c-Myc plays a direct...

  13. a549 human lung: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Human (more) Weems, Jessica Marie 2010-01-01 26 KILLING OF TARGET CELLS DUE TO RADON PROGENY IN THE HUMAN LUNG Physics Websites Summary: to the epidemiologically derived value...

  14. Targets of Balancing Selection in the Human Genome Aida M. Andres,* 1

    E-Print Network [OSTI]

    Nielsen, Rasmus

    proposed for several human diseases, including the ß-globin gene and sickle cell anemia (Pasvol et al. 1978

  15. Nuclear localization of pyrroleimidazole polyamidefluorescein conjugates in cell culture

    E-Print Network [OSTI]

    Dervan, Peter B.

    - jugates were synthesized and assayed for cellular localization. Thirteen cell lines, representing 11 human cancers, one human transformed kidney cell line, and one murine leukemia cell line, were treated with 5 M cell lines tested. The localization profiles of several other conjugates suggest that pyrrole

  16. Video Capture of Skin Motion using Calibrated Fabien DELLAS

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    3D mesh can easily be integrated and adapted in a sequence of an animated virtual human. We of virtual humans remains exhaustive and tedious. For animating virtual characters, 3D animators work similarly as drawers for car- toons, that implies hundreds of hours for only few seconds of animation

  17. ageing human colonic: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    : 0469-9 12;5122013 Postdoctoral position for the Thalis Program Human cells Genome surveillance, Proteasome Mitochondrial metabolism Mitochondria & Lysosomes Genome 213...

  18. autologous human peripheral: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    significant. Two subjects continued to have de- creased cell Lieberman, Judy 6 Helicobacter pylori Induces Activation of Human Peripheral cd+ T Lymphocytes CiteSeer...

  19. ageing human fibroblasts: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    STUDY OF DNA DOUBLE-STRAND BREAKS IN BYSTANDER PRIMARY HUMAN FIBROBLASTS L. B. Smilenov-or-nothing manner(7) . Bystander cells exhibit a variety of characteristics of...

  20. ancient human dna: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    STUDY OF DNA DOUBLE-STRAND BREAKS IN BYSTANDER PRIMARY HUMAN FIBROBLASTS L. B. Smilenov-or-nothing manner(7) . Bystander cells exhibit a variety of characteristics of...

  1. acid induces human: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    STUDY OF DNA DOUBLE-STRAND BREAKS IN BYSTANDER PRIMARY HUMAN FIBROBLASTS L. B. Smilenov-or-nothing manner(7) . Bystander cells exhibit a variety of characteristics of...

  2. Metastatic potential of melanoma cells is not affected by electrochemotherapy

    E-Print Network [OSTI]

    Ljubljana, University of

    Metastatic potential of melanoma cells is not affected by electrochemotherapy Vesna Todorovica in the treatment of malignant melanoma. However, the effect of electrochemotherapy on the metastatic potential of human malignant melanoma cells. Cells treated by electrochemotherapy with cisplatin were tested

  3. Icariin stimulates angiogenesis by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent signal pathways in human endothelial cells

    SciTech Connect (OSTI)

    Chung, Byung-Hee [Vascular System Research Center and Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chunchon, Kangwon-do 200-701 (Korea, Republic of); Division of Food Biotechnology, School of Biotechnology, Kangwon National University, Chunchon, Kangwon-do (Korea, Republic of); Kim, Jong-Dai [Division of Food Biotechnology, School of Biotechnology, Kangwon National University, Chunchon, Kangwon-do (Korea, Republic of); Kim, Chun-Ki; Kim, Jung Huan [Vascular System Research Center and Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chunchon, Kangwon-do 200-701 (Korea, Republic of); Won, Moo-Ho [Department of Anatomy, School of Medicine, Hallym University, Chunchon, Kangwon-do (Korea, Republic of); Lee, Han-Soo [Vascular System Research Center and Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chunchon, Kangwon-do 200-701 (Korea, Republic of); Dong, Mi-Sook [School of Life Sciences and Biotechnology, Korea University, 1, 5-Ka, Anam-dong, Sungbuk-ku, Seoul 136-701 (Korea, Republic of); Ha, Kwon-Soo [Vascular System Research Center and Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chunchon, Kangwon-do 200-701 (Korea, Republic of); Kwon, Young-Geun [Department of Biochemistry, College of Sciences, Yonsei University, Seoul (Korea, Republic of); Kim, Young-Myeong [Vascular System Research Center and Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chunchon, Kangwon-do 200-701 (Korea, Republic of)], E-mail: ymkim@kangwon.ac.kr

    2008-11-14T23:59:59.000Z

    We investigated the molecular effect and signal pathway of icariin, a major flavonoid of Epimedium koreanum Nakai, on angiogenesis. Icariin stimulated in vitro endothelial cell proliferation, migration, and tubulogenesis, which are typical phenomena of angiogenesis, as well as increased in vivo angiogenesis. Icariin activated the angiogenic signal modulators, ERK, phosphatidylinositol 3-kinase (PI3K), Akt, and endothelial nitric oxide synthase (eNOS), and increased NO production, without affecting VEGF expression, indicating that icariin may directly stimulate angiogenesis. Icariin-induced ERK activation and angiogenic events were significantly inhibited by the MEK inhibitor PD98059, without affecting Akt and eNOS phosphorylation. The PI3K inhibitor Wortmannin suppressed icariin-mediated angiogenesis and Akt and eNOS activation without affecting ERK phosphorylation. Moreover, the NOS inhibitor NMA partially reduced the angiogenic activity of icariin. These results suggest that icariin stimulated angiogenesis by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent signal pathways and may be a useful drug for angiogenic therapy.

  4. Density dependence of the symmetry energy from neutron skin thickness in finite nuclei

    SciTech Connect (OSTI)

    Vinas, X.; Centelles, M.; Roca-Maza, X.; Warda, M. [Departament d'Estructura i Conastituents de la Materia and Institut de Ciencies del Cosmos, Facultat de Fisica, Universitat de Barcelona, Marti i Franques 1, 08028, Barcelona (Spain); Instituto Nazionale di Fisica Nucleare, Sezione di Milano , Via Celoria 16, I-20133 Milano (Italy); Katedra Fizyki Teoretycznej, Uniwersytet Marii Curie-Skodowskiej ul. Radziszewskiego 10, 20-031 Lublin (Poland)

    2012-10-20T23:59:59.000Z

    The density dependence of the symmetry energy, characterized by the parameter L, is studied using information provided by the neutron skin thickness in finite nuclei. An estimate of L is obtained from experimental data of antiprotonic atoms. We also discuss the ability of parity violating electron scatering to obtain information about the neutron skin thickness in {sup 208}Pb.

  5. ON THE INFLUENCE OF THE GEOMETRY ON SKIN EFFECT IN ELECTROMAGNETISM

    E-Print Network [OSTI]

    Dauge, Monique

    ON THE INFLUENCE OF THE GEOMETRY ON SKIN EFFECT IN ELECTROMAGNETISM GABRIEL CALOZ, MONIQUE DAUGE #12;2 GABRIEL CALOZ, MONIQUE DAUGE, ERWAN FAOU, VICTOR P´ERON electromagnetic field at high is larger ­ and here the sign of the curvature has a major influence, which means that the skin depth

  6. ON THE INFLUENCE OF THE GEOMETRY ON SKIN EFFECT IN ELECTROMAGNETISM

    E-Print Network [OSTI]

    Faou, Erwan

    ON THE INFLUENCE OF THE GEOMETRY ON SKIN EFFECT IN ELECTROMAGNETISM GABRIEL CALOZ, MONIQUE DAUGE conductivity are proved in [3], whereas in the note [4] a 1 #12;2 GABRIEL CALOZ, MONIQUE DAUGE, ERWAN FAOU of the curvature has a major influence, which means that the skin depth is larger in convex than in concave

  7. Theory of thin-skin eddy-current interaction with surface cracks N. Harfielda)

    E-Print Network [OSTI]

    Bowler, John R.

    Theory of thin-skin eddy-current interaction with surface cracks N. Harfielda) and J. R. Bowler; accepted for publication 14 July 1997 Eddy-current non-destructive evaluation is commonly performed of a typical crack. A thin-skin analysis of eddy currents is presented in which the electromagnetic fields

  8. Antenna-based "Smart Skin" Sensors for Sustainable, Wireless Sensor Networks

    E-Print Network [OSTI]

    Tentzeris, Manos

    Antenna-based "Smart Skin" Sensors for Sustainable, Wireless Sensor Networks Hoseon Leet, George-less, or sustainable, wireless sensor networks with "smart skin" sensor nodes. These sensors are highly applicable a wireless sensor network with smart sensors requires a lot of power due to the mass number of sensor nodes

  9. Assisting diagnosis of melanoma through the "noninvasive biopsy" of skin lesions

    E-Print Network [OSTI]

    Claridge, Ela

    Assisting diagnosis of melanoma through the "noninvasive biopsy" of skin lesions Symon D-180. #12;Assisting diagnosis of melanoma through the "noninvasive biopsy" of skin lesions Symon Cotton1 to ensure a good prognosis, malignant melanoma needs to be diagnosed whilst the level of invasion

  10. Recently, doctors in Texas have been seeing an increasing number of patients with skin

    E-Print Network [OSTI]

    that kill bacteria), also called methicillin-resistant Staphylococcus aureus-- "MRSA." The Texas Department this is happening and how to prevent antibiotic (drug) resistant Staph/MRSA skin infections from spreading. What is a Staph/MRSA skin infection? It can be a pimple, rash, boil, or an open wound. Staph/MRSA is often

  11. Towards a Minimal Architecture for a Printable, Modular, and Robust Sensing Skin

    E-Print Network [OSTI]

    Fearing, Ron

    . Bachrach, and R.S. Fearing Abstract-- This work presents a low-complexity modular sensor grid architecture to provide a smart skin to non-convex shapes, such as a robot body and legs. To configure a sensing skin shaped by arbitrary cuts and rapid changes in designs, we use a wavefront planning approach to generate

  12. Enhancers and super-enhancers in human disease and therapy

    E-Print Network [OSTI]

    Hoke, Heather Ashley

    2014-01-01T23:59:59.000Z

    The human body is made up of a diverse array of cell types, each with specialized properties and functions that support the organism as a whole. Despite this variability, with few exceptions, these cells contain the same ...

  13. Collaborators and Funding Photodynamic therapy (PDT) has been proven to be effective treatment for non-melanoma skin

    E-Print Network [OSTI]

    Greenaway, Alan

    for non-melanoma skin cancers with excellent cosmetic outcome. PDT treatment and diagnostics apply light - solution for non-melanoma skin cancer treatment III Fluorescence imaging camera for PDT diagnostics I

  14. 2,6-Dithiopurine, a nucleophilic scavenger, protects against mutagenesis in mouse skin treated in vivo with 2-(chloroethyl) ethyl sulfide, a mustard gas analog

    SciTech Connect (OSTI)

    Boulware, Stephen [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States)] [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States); Fields, Tammy; McIvor, Elizabeth; Powell, K. Leslie; Abel, Erika L. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States)] [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States); Vasquez, Karen M. [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States)] [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States); MacLeod, Michael C., E-mail: mcmacleod@mdanderson.org [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States)

    2012-09-01T23:59:59.000Z

    Sulfur mustard [bis(2-chloroethyl)sulfide, SM] is a well-known DNA-damaging agent that has been used in chemical warfare since World War I, and is a weapon that could potentially be used in a terrorist attack on a civilian population. Dermal exposure to high concentrations of SM produces severe, long-lasting burns. Topical exposure to high concentrations of 2-(chloroethyl) ethyl sulfide (CEES), a monofunctional analog of SM, also produces severe skin lesions in mice. Utilizing a genetically engineered mouse strain, Big Blue, that allows measurement of mutation frequencies in mouse tissues, we now show that topical treatment with much lower concentrations of CEES induces significant dose- and time-dependent increases in mutation frequency in mouse skin; the mutagenic exposures produce minimal toxicity as determined by standard histopathology and immunohistochemical analysis for cytokeratin 6 and the DNA-damage induced phosphorylation of histone H2AX (?-H2AX). We attempted to develop a therapeutic that would inhibit the CEES-induced increase in mutation frequency in the skin. We observe that multi-dose, topical treatment with 2,6-dithiopurine (DTP), a known chemical scavenger of CEES, beginning 1 h post-exposure to CEES, completely abolishes the CEES-induced increase in mutation frequency. These findings suggest the possibility that DTP, previously shown to be non-toxic in mice, may be useful as a therapeutic agent in accidental or malicious human exposures to SM. -- Highlights: ? 200 mM 2-(chloroethyl) ethyl sulfide (CEES) induces mutations in mouse skin. ? This dose of CEES is not overtly toxic, as assayed by histopathology. ? 2,6-Dithiopurine (DTP), applied after CEES-treatment, abolishes CEES-mutagenesis. ? This supports the idea that sulfur mustards exhibit long biological half-lives.

  15. Human Ecology Human ecology Research

    E-Print Network [OSTI]

    Wang, Z. Jane

    Channel, Latin America. STUDIOS Architecture. #12;HUMAN ECOLOGY · APRIL 2005 1 Lisa Staiano-Coico, Ph Frey spins a green alternative for textiles. Fibers from rapidly renewable materials

  16. Asymmetric lateral distribution of melanoma and Merkel cell carcinoma in the United States

    E-Print Network [OSTI]

    Nghiem, Paul

    Asymmetric lateral distribution of melanoma and Merkel cell carcinoma in the United States Kelly G incidences of two ultraviolet-linked skin cancers, malignant melanoma (MM) and Merkel cell carcinoma (MCC and MCC). In all, 53% of arm melanomas, 51% of facial melanomas, and 52% of leg melanomas presented

  17. Plasmacytoid dendritic cells and dermatological disorders : focus on their role in autoimmunity and tumors

    E-Print Network [OSTI]

    Boyer, Edmond

    in autoimmunity and tumors Short title : PDC and skin Charles Julie 1,2,3 , Chaperot Laurence 2,3 , Salameire dendritic cells (PDC). The presence of PDC, cells capable of producing large quantities of interferon alpha conditions. Thereby, PDC have been observed in inflammatory immunoallergic dermatological disorders

  18. The second skin approach : skin strain field analysis and mechanical counter pressure prototyping for advanced spacesuit design

    E-Print Network [OSTI]

    Bethke, Kristen (Kristen Ann)

    2005-01-01T23:59:59.000Z

    The primary aim of this thesis is to advance the theory of advanced locomotion mechanical counter pressure (MCP) spacesuits by studying the changes in the human body shape during joint motion. Two experiments take advantage ...

  19. Sensitivity of the electric dipole polarizability to the neutron skin thickness in {sup 208}Pb

    SciTech Connect (OSTI)

    Roca-Maza, X.; Agrawal, B. K.; Colo, G.; Nazarewicz, W.; Paar, N.; Piekarewicz, J.; Reinhard, P.-G.; Vretenar, D. [INFN, sezione di Milano, via Celoria 16, I-20133 Milano (Italy); Saha Institute of Nuclear Physics, Kolkata 700064 (India); Dipartimento di Fisica, Universita degli Studi di Milano and INFN, Sezione di Milano, 20133 Milano (Italy); Department of Physics and Astronomy, University of Tennessee, Knoxville, Tennessee 37996 (United States) and Institute of Theoretical Physics, University of Warsaw, Hoza 69, PL-00-681 Warsaw (Poland); Physics Department, Faculty of Science, University of Zagreb, Zagreb (Croatia); Department of Physics, Florida State University, Tallahassee, FL 32306 (United States); Institut fuer Theoretische Physik II, Universitaet Erlangen-Nuernberg, Staudtstrasse 7, D-91058 Erlangen (Germany); Physics Department, Faculty of Science, University of Zagreb, Zagreb (Croatia)

    2012-10-20T23:59:59.000Z

    The static dipole polarizability, {alpha}{sub D}, in {sup 208}Pb has been recently measured with highresolution via proton inelastic scattering at the Research Center for Nuclear Physics (RCNP) [1]. This observable is thought to be intimately connected with the neutron skin thickness, r{sub skin}, of the same nucleus and, more fundamentally, it is believed to be associated with the density dependence of the nuclear symmetry energy. The impact of r{sub skin} on {alpha}{sub D} in {sup 208}Pb is investigated and discussed on the basis of a large and representative set of relativistic and non-relativistic nuclear energy density functionals (EDF) [2].

  20. A common supersolid low-density skin sliperizing ice and toughening water surface

    E-Print Network [OSTI]

    Xi Zhang; Yongli Huang; Zengsheng Ma; Yichun Zhou; Weitao Zheng; Ji Zhou; Chang Q. Sun

    2014-08-15T23:59:59.000Z

    Skins of water and ice share the same attribute of supersolidity characterized by the identical H-O vibration frequency of 3450 cm-1. Molecular undercoordination and inter-electron-pair repulsion shortens the H-O bond and lengthen the O:H nonbond, leading to a dual process of nonbonding electron polarization. This relaxation-polarization process enhances the dipole moment, elasticity,viscosity, thermal stability of these skins with 25% density loss, which is responsible for the hydrophobicity and toughness of water skin and for the slippery of ice.

  1. Predicting the Occurrence of Cosmetic Defects in Automotive Skin Panels

    SciTech Connect (OSTI)

    Hazra, S.; Williams, D.; Roy, R. [University of Warwick, Gibbet Hill Road, Coventry CV4 7AL (United Kingdom); Aylmore, R.; Allen, M.; Hollingdale, D. [Land Rover, Banbury Rd, Gaydon, Warwick, CV35 0RR (United Kingdom)

    2011-05-04T23:59:59.000Z

    The appearance of defects such as 'hollows' and 'shock lines' can affect the perceived quality and attractiveness of automotive skin panels. These defects are the result of the stamping process and appear as small, localized deviations from the intended styling of the panels. Despite their size, they become visually apparent after the application of paint and the perceived quality of a panel may become unacceptable. Considerable time is then dedicated to minimizing their occurrence through tool modifications. This paper will investigate the use of the wavelet transform as a tool to analyze physically measured panels. The transform has two key aspects. The first is its ability to distinguish small scale local defects from large scale styling curvature. The second is its ability to characterize the shape of a defect in terms of its wavelength and a 'correlation value'. The two features of the transform enable it to be used as a tool for locating and predicting the severity of defects. The paper will describe the transform and illustrate its application on test cases.

  2. Simulation of Electron-Beam Irradiation of Skin Tissue Model

    SciTech Connect (OSTI)

    Miller, John H.; Suleiman, Atef; Chrisler, William B.; Sowa, Marianne B.

    2011-01-03T23:59:59.000Z

    Monte Carlo simulation of electrons stopping in liquid water was used to model the penetration and dose distribution of electron beams incident on the full-thickness EpiDermTM skin model (MatTek, Ashland, VA). This 3D tissue model has a fully developed basement membrane separating an epidermal layer of keratinocytes in various stages of differentiation from a dermal layer of fibroblast embedded in collagen. The simulations were motivated by a desire to selectively expose the epidermal layer to low linear-energy-transfer (LET) radiation in the presence of a non-irradiated dermal layer. Using the variable energy electron microbeam at the Pacific Northwest National Laboratory (PNNL) as a model of device characteristics and irradiation geometry, we find that at the highest beam energy available (90 keV), the estimated 90th percentile of penetration remains in the epidermal layer. To investigate the depth-dose distribution, we calculated lineal energy spectra for 10um thick layers near the 10th, 50th, and 90th percentile of penetration by the 90 keV electron beam. Biphasic spectra showed an increasing component of "stoppers" with increasing depth. Despite changes in the lineal energy spectra, the main effect on dose deposition with increasing depth is the screening effect of tissue above the layer of interest.

  3. Human dopamine receptor and its uses

    DOE Patents [OSTI]

    Civelli, Olivier (Portland, OR); Van Tol, Hubert Henri-Marie (Toronto, CA)

    1999-01-01T23:59:59.000Z

    The present invention is directed toward the isolation, characterization and pharmacological use of the human D4 dopamine receptor. The nucleotide sequence of the gene corresponding to this receptor and alleleic variant thereof are provided by the invention. The invention also includes recombinant eukaryotic expression constructs capable of expressing the human D4 dopamine receptor in cultures of transformed eukaryotic cells. The invention provides cultures of transformed eukaryotic cells which synthesize the human D4 dopamine receptor, and methods for characterizing novel psychotropic compounds using such cultures.

  4. Structural/functional relationships between internal and external MSH receptors: modulation of expression in Cloudman melanoma cells by UVB radiation

    SciTech Connect (OSTI)

    Chakraborty, A.K.; Orlow, S.J.; Bolognia, J.L.; Pawelek, J.M. (Department of Dermatology, Yale University School of Medicine, New Haven, CT (USA))

    1991-04-01T23:59:59.000Z

    Expression of internal receptors for MSH is an important criterion for responsiveness to MSH by Cloudman melanoma cells. Here, we show that internal and external receptors for MSH are of identical molecular weights (50-53 kDa) and share common antigenic determinants, indicating a structural relationship between the 2 populations of molecules. The internal receptors co-purified with a sub-cellular fraction highly enriched for small vesicles, many of which were coated. Ultraviolet B light (UVB) acted synergistically with MSH to increase tyrosinase activity and melanin content of cultured Cloudman melanoma cells, consistent with previous findings in the skin of mice and guinea pigs. Preceding the rise in tyrosinase activity in cultured cells, UVB elicited a decrease in internal MSH binding sites and a concomitant increase in external sites. The time frame for the UVB effects on MSH receptors and melanogenesis, 48 hours, was similar to that for a response to solar radiation in humans. Together, the results indicate a key role for MSH receptors in the induction of melanogenesis by UVB and suggest a potential mechanism of action for UVB: redistribution of MSH receptors with a resultant increase in cellular responsiveness to MSH.

  5. FRACTURE OF SKIN-STIFFENER INTERSECTIONS IN COMPOSITE WIND TURBINE BLADE STRUCTURES

    E-Print Network [OSTI]

    FRACTURE OF SKIN-STIFFENER INTERSECTIONS IN COMPOSITE WIND TURBINE BLADE STRUCTURES by Darrin John to the other graduate students in the composite materials group for your smiles and friendships over the past Material .........................................................................................10

  6. Meeting report for the 1st skin microbiota workshop, Boulder, CO October 15-16 2012

    E-Print Network [OSTI]

    Gilbert, Jack A

    This report details the outcome of the 1st Skin Microbiota Workshop, Boulder, CO, held on October 15th-16th 2012. The workshop was arranged to bring Department of Defense personnel together with experts in microbial ecology, ...

  7. A Systematic Study of Matrix Acidizing Treatments Using Skin Monitoring Method

    E-Print Network [OSTI]

    Pandya, Nimish

    2012-07-16T23:59:59.000Z

    The goal of this work was to evaluate matrix acidizing treatments of vertical and horizontal wells in carbonate reservoirs. Twenty field cases for acidizing treatments were analyzed by evaluating the skin factor evolution from on-site rate...

  8. REFLEXIVE COLLISION RESPONSE WITH VIRTUAL SKIN Roadmap Planning Meets Reinforcement Learning

    E-Print Network [OSTI]

    Förster, Alexander

    REFLEXIVE COLLISION RESPONSE WITH VIRTUAL SKIN Roadmap Planning Meets Reinforcement Learning Svizzera italiana, CH-6928 Manno-Lugano Keywords: Roadmap Planning: Reinforcement Learning: Collision to a changing environment, but not both. This work proposes a simple integration of roadmap planning

  9. In Vivo characterization of skin using a weiner nonlinear stochastic identification method

    E-Print Network [OSTI]

    Chen, Yi

    This paper describes an indentometer device used to identify the linear dynamic and nonlinear properties of skin and underlying tissue using an in vivo test. The device uses a Lorentz force actuator to apply a dynamic force ...

  10. Certain basic surgical principles of full-thickness free skin grafts in the dog

    E-Print Network [OSTI]

    Trevino, Gilberto Stephenson

    1959-01-01T23:59:59.000Z

    THICK GRAFT FULL THICKNESS GRAFT DERMIS ~i-/) HYPODERMIS 8 grafts 1n use todayo, . = - - Co HISTOHI QP SKIE GBAPTINQ ?' Hux earliest efforts to utilize skin for the reparation of integu- mentary defects vere undertalaen centuries ago...

  11. Depth data improves non-melanoma skin lesion segmentation and diagnosis 

    E-Print Network [OSTI]

    Li, Xiang

    2012-06-25T23:59:59.000Z

    Examining surface shape appearance by touching and observing a lesion from different points of view is a part of the clinical process for skin lesion diagnosis. Motivated by this, we hypothesise that surface shape embodies ...

  12. Is the duration of skin disease visits decreasing in the united states?

    E-Print Network [OSTI]

    Davis, Scott A; Feldman, Steven R; Fleischer Jr., Alan B

    2015-01-01T23:59:59.000Z

    on fridays. J Dermatolog Treat 2013 Dec;24(6):405-7. [PMID:treatment. J Dermatolog Treat 2014 Dec;25(6):453-8. [PMID:Although non-dermatologists treat about half of all skin

  13. Design and fabrication of an optical pressure micro sensor for skin mechanics studies

    E-Print Network [OSTI]

    Kumar, Siddarth

    2006-01-01T23:59:59.000Z

    The mechanics of skin is as central to touch as optics is to vision and acoustics is to hearing. With the advent of novel imaging technologies such as the Optical Coherence Tomography (OCT), we are now able to view structures ...

  14. Has a thick neutron skin in ${}^{208}$Pb been ruled out?

    E-Print Network [OSTI]

    Fattoyev, F J

    2013-01-01T23:59:59.000Z

    The Lead Radius Experiment (PREX) has provided the first model-independent evidence in favor of a neutron-rich skin in ${}^{208}$Pb. Although the error bars are large, the reported large central value of 0.33\\,fm is particularly intriguing. To test whether such a thick neutron-skin in ${}^{208}$Pb is already incompatible with laboratory experiments or astrophysical observations, we employ relativistic models with neutron-skin thickness in ${}^{208}$Pb ranging from 0.16 to 0.33 fm to compute ground state properties of finite nuclei, their collective monopole and dipole response, and mass-{\\sl vs}-radius relations for neutron stars. No compelling reason was found to rule out models with large neutron skins in ${}^{208}$Pb from the set of observables considered in this work.

  15. FATIGUE OF SKIN-STIFFENER INTERSECTIONS IN COMPOSITE WIND TURBINE BLADE STRUCTURES

    E-Print Network [OSTI]

    FATIGUE OF SKIN-STIFFENER INTERSECTIONS IN COMPOSITE WIND TURBINE BLADE STRUCTURES by Robert B in the Instron and Composite Laboratories toward the end of the experimental research. Finally, special thanks

  16. Development and Construction of Bioclimatic Double Skin Active Facade for Hot and Humid Climate of UAE 

    E-Print Network [OSTI]

    Karbor, R. G.; Mohamed, I.

    2010-01-01T23:59:59.000Z

    tracking venetian blinds, LED (light emitting diodes) lighting and Building Management system. 1.01 Modeling And Simulation Of Double Skin Active Facade The modeling and simulation of the Double Skin Fa?ade Cavity is a complicated task, since... sweating/condensation on the water coil. 3.06 LED (Light Emitting Diode) Lighting The building is illuminated using extremely energy efficient LED?s which last 5 times as long as fluorescents and 50 times longer than typical incandescent. So...

  17. Development and Construction of Bioclimatic Double Skin Active Facade for Hot and Humid Climate of UAE

    E-Print Network [OSTI]

    Karbor, R. G.; Mohamed, I.

    2010-01-01T23:59:59.000Z

    tracking venetian blinds, LED (light emitting diodes) lighting and Building Management system. 1.01 Modeling And Simulation Of Double Skin Active Facade The modeling and simulation of the Double Skin Fa?ade Cavity is a complicated task, since... sweating/condensation on the water coil. 3.06 LED (Light Emitting Diode) Lighting The building is illuminated using extremely energy efficient LED?s which last 5 times as long as fluorescents and 50 times longer than typical incandescent. So...

  18. Polymers, both natural and synthetic, play an integral role in our daily lives. Naturally-occurring polymers include cellulose (mentioned in gun cotton demo), rubber, skin, hair,

    E-Print Network [OSTI]

    Weston, Ken

    . Naturally- occurring polymers include cellulose (mentioned in gun cotton demo), rubber, skin, hair, DNA, etc

  19. Monochromosomal hybrids for the analysis of the human genome

    SciTech Connect (OSTI)

    Athwal, R.S.

    1990-01-01T23:59:59.000Z

    In this research project the authors proposed to develop rodent/human hybrid cell lines each containing a single different human chromosome. The human chromosomes will be marked with Ecogpt and stably maintained by selection in the hybrid cells. The experimental approach to produce the proposed cell lines involve the following: they will first transfer a cloned selectable marker, Ecogpt (an E. coli gene for xanthine-guanine phosphoribosyltransferase: XGPRT) to normal diploid human cells using a retroviral vector. The transferred gene will integrate at random into multiple sites in the recipient cell genome. Clonal cell lines from independent transgenotes will each carry the selectable marker integrated into a different site and perhaps a different chromosome. The chromosome carrying the selectable marker will then be transferred further to mouse cells by microcell fusion. In addition they also use directed integration of Ecogpt into the chromosome present in rodent cells, otherwise not marked with a selectable marker. This allows them to complete the bank of proposed cell line. The human chromosome, since it will be marked with a selectable marker, can be transferred to any other cell line of interest for complementation analysis. Clones of each cell line, containing varying size segments of the same chromosome produced by selection for the retention or loss of the selectable marker following x-irradiation or by metaphase chromosome transfer method will facilitate physical mapping and determination of gene order on a chromosome. 1 fig.

  20. Relevance of in vivo models in melanoma skin cancer

    SciTech Connect (OSTI)

    Setlow, R.B.

    1995-12-31T23:59:59.000Z

    A discussion of possible wavelength dependence of induction of cutaneous malignant melanoma (CMM) is provided. Strengths and weaknesses of various experimental approaches to better understanding of the prevalence of CMM in different human populations including latitude effects are compared. Further the advantages and limitations of the use of the laboratory opossum (Monodelphis domestic), transgenic mice containing SV40 ongogene sequences under tyrosinase promoter control, and a backcross hybrid fish of the genus Xenophorus are contrasted.

  1. Restoration of normal phenotype in cancer cells

    DOE Patents [OSTI]

    Bissell, M.J.; Weaver, V.M.

    1998-12-08T23:59:59.000Z

    A method for reversing expression of malignant phenotype in cancer cells is described. The method comprises applying {beta}{sub 1} integrin function-blocking antibody to the cells. The method can be used to assess the progress of cancer therapy. Human breast epithelial cells were shown to be particularly responsive. 14 figs.

  2. Restoration of normal phenotype in cancer cells

    DOE Patents [OSTI]

    Bissell, Mina J. (Berkeley, CA); Weaver, Valerie M. (Oakland, CA)

    1998-01-01T23:59:59.000Z

    A method for reversing expression of malignant phenotype in cancer cells is described. The method comprises applying .beta..sub.1 integrin function-blocking antibody to the cells. The method can be used to assess the progress of cancer therapy. Human breast epithelial cells were shown to be particularly responsive.

  3. Transgene Excision Has No Impact on In Vivo Integration of Human iPS Derived Neural Precursors

    E-Print Network [OSTI]

    Major, Tamara

    The derivation of induced human pluripotent stem cells (hiPS) has generated significant enthusiasm particularly for the prospects of cell-based therapy. But there are concerns about the suitability of iPS cells for in vivo ...

  4. Influence of neutron-skin thickness on $?^{-}/?^{+}$ ratio in Pb+Pb collisions

    E-Print Network [OSTI]

    Gao-Feng Wei; Bao-An Li; Jun Xu; Lie-Wen Chen

    2015-01-21T23:59:59.000Z

    Within an isospin- and momentum-dependent transport model IBUU11 using as an input nucleon density profiles from Hartree-Fock calculations based on a modified Skyrme-like (MSL) model, we study the influence of the uncertainty of the neutron skin thickness on the $\\pi^{-}/\\pi^{+}$ ratio in both central and peripheral Pb+Pb collisions at beam energies of 400 MeV/nucleon and 1000 MeV/nucleon. Within the current experimental uncertainty range of neutron skin in $^{208}$Pb, while the neutron skin effect on the \\rpi ratio is negligible in central reactions at both energies, it increases gradually with increasing impact parameter and becomes comparable with or even larger than the symmetry energy effect in peripheral collisions especially at 400 MeV/nucleon. Moreover, we found that while the \\rpi ratio is larger with a softer \\esym in central collisions, above certain impact parameters depending on the size of the neutron skin, a stiffer \\esym can lead to a larger \\rpi ratio as most of the pions are produced at densities below the saturation density in these peripheral reactions. Thus, a clear impact parameter selection is important to extract reliable information about the \\esym at suprasaturation densities (size of neutron skin) from the $\\pi^-/\\pi^+$ ratio in central (peripheral) heavy-ion collisions.

  5. PI Control of Gene Expression in Tumorous Cell Lines

    E-Print Network [OSTI]

    Mendonca, Rouella J.

    2010-01-16T23:59:59.000Z

    cancer cell line genes behave more like their Human Embryonic Kidney cell line counterparts. Two methods of intervention were introduced. The first method was the simpler on-off control intervention while the second method used a more advanced...

  6. Detecting and molecular profiling cancer cells in patients

    E-Print Network [OSTI]

    Peterson, Vanessa M. (Vanessa Marie)

    2013-01-01T23:59:59.000Z

    Although tumor cells obtained from human patients by surgical biopsy, image-guided intervention, blood draws or fluid drainage (paracentesis, thoracentesis) are a valuable source for analyzing tumor cells, conventional ...

  7. HER receptor-mediated dynamic signalling in breast cancer cells 

    E-Print Network [OSTI]

    Hu, Huizhong

    2011-07-05T23:59:59.000Z

    The dynamics of cell signalling are critical to cell fate decisions. Human Epidermal growth factor Receptors (HERs)-mediated Ras/Raf/MEK/ERK and PI3K/Akt signalling cascades relay extracellular signals from the plasma ...

  8. Illusory Sense of Human Touch from a Warm and Soft Artificial Hand

    E-Print Network [OSTI]

    Cabibihan, John-John; Srinivasa, Yeshwin Mysore; Chan, Mark Aaron; Muruganantham, Arrchana

    2015-01-01T23:59:59.000Z

    To touch and be touched are vital to human development, well being, and relationships. However, to those who have lost their arms and hands due to accident or war, touching becomes a serious concern that often leads to psychosocial issues and social stigma. In this paper, we demonstrate that the touch from a warm and soft rubber hand can be perceived by another person as if the touch were coming from a human hand. We describe a three step process toward this goal. First, we made participants select artificial skin samples according to their preferred warmth and softness characteristics. At room temperature, the preferred warmth was found to be 28.4 deg C at the skin surface of a soft silicone rubber material that has a Shore durometer value of 30 at the OO scale. Second, we developed a process to create a rubber hand replica of a human hand. To compare the skin softness of a human hand and artificial hands, a robotic indenter was employed to produce a softness map by recording the displacement data when const...

  9. Increasing IFN-[gamma] productivity in CHO cells through CDK inhibition

    E-Print Network [OSTI]

    McClain, David Alan

    2010-01-01T23:59:59.000Z

    Approximately 60-70% of all recombinant human glycoproteins are produced in Chinese Hamster Ovary (CHO) cells. Production in CHO cells, however, is often plagued by low productivity when compared with other host cell lines, ...

  10. Generation of Isogenic Pluripotent Stem Cells Differing Exclusively at Two Early Onset Parkinson Point Mutations

    E-Print Network [OSTI]

    Soldner, Frank

    Patient-specific induced pluripotent stem cells (iPSCs) derived from somatic cells provide a unique tool for the study of human disease, as well as a promising source for cell replacement therapies. One crucial limitation ...

  11. Skin: Major target organ of allergic reactions to small molecular weight compounds

    SciTech Connect (OSTI)

    Merk, Hans F. [Department of Dermatology and Allergology, Univ.-Hospital, RWTH Aachen, Pauwelsstr. 30, D-52074 Aachen (Germany)], E-mail: hans.merk@post.rwth-aachen.de; Baron, Jens M.; Neis, Mark M.; Obrigkeit, Daniela Hoeller [Department of Dermatology and Allergology, Univ.-Hospital, RWTH Aachen, Pauwelsstr. 30, D-52074 Aachen (Germany); Karlberg, Ann-Therese [Dermatochemistry and Skin Allergy, Department of Chemistry, Goeteborg University, SE-412 96 Goeteborg (Sweden)

    2007-11-01T23:59:59.000Z

    Skin is a major target organ for allergic reactions to small molecular weight compounds. Drug allergic reactions may be life-threatening such as in the case of anaphylactic reactions or bullous drug reactions and occur in about 5% of all hospitalized patients. Allergic contact dermatitis has an enormous influence on the social life of the patient because it is the most frequent reason for occupational skin diseases and the treatment and prevention of this disease cost approximately Euro 3 billion per year in Germany. The different proposed pathophysiological pathways leading to a drug eruption are discussed in this paper. All major enzymes which are involved in the metabolism of xenobiotica were shown to be present in skin. Evidence supporting the role of metabolism in the development of drug allergy and allergic contact dermatitis is demonstrated in the example of sulphonamides and fragrances.

  12. Regulation of insulin-like growth factor binding protein-4 in Ah responsive and Ah nonresponsive human breast cancer cells by 17 B-estradiol and 2,3,7,8 tetrachlorodibenzo-p-dioxin 

    E-Print Network [OSTI]

    Schrope, Katherine Eillene

    1997-01-01T23:59:59.000Z

    were not affected 24 hours after treatment. Aryl-hydrocarbon receptor (Ah) nonresponsive cells (BaP MCF-7 and T47D5 cells) were utilized to investigate the role of the Ah-receptor in the regulation of IGFBP-4 by TCDD. Western ligand blot analysis...

  13. Chronic cellular responses of rat skin to 13 Mev proton irradiation

    E-Print Network [OSTI]

    Hinkle, Donald King

    1966-01-01T23:59:59.000Z

    CHRONIC CELLULAR RESPONSES OF RAT SKIN TO 13 MEV PROTON IRRADIATION A Thesis by DONALD KING HINKLE, D. V. M. Submitted to the Graduate College of the Texas AErM University in partial fulfillment of the requirements for the degree of MASTER... OF SCIENCE August 1966 Major Subject: Laboratory Animal Medicine CHRONIC CELLULAR RESPONSES OF RAT SKIN TO 13 MEV PROTON IRRADIATION A Thesis by DONALD KING HINKLE, D. V. M. Submitted to the Graduate College of the Texas ARM University in partial...

  14. Limitations of the TG-43 formalism for skin high-dose-rate brachytherapy dose calculations

    SciTech Connect (OSTI)

    Granero, Domingo, E-mail: dgranero@eresa.com [Department of Radiation Physics, ERESA, Hospital General Universitario, 46014 Valencia (Spain)] [Department of Radiation Physics, ERESA, Hospital General Universitario, 46014 Valencia (Spain); Perez-Calatayud, Jose [Radiotherapy Department, La Fe University and Polytechnic Hospital, Valencia 46026 (Spain)] [Radiotherapy Department, La Fe University and Polytechnic Hospital, Valencia 46026 (Spain); Vijande, Javier [Department of Atomic, Molecular and Nuclear Physics, University of Valencia, Burjassot 46100, Spain and IFIC (UV-CSIC), Paterna 46980 (Spain)] [Department of Atomic, Molecular and Nuclear Physics, University of Valencia, Burjassot 46100, Spain and IFIC (UV-CSIC), Paterna 46980 (Spain); Ballester, Facundo [Department of Atomic, Molecular and Nuclear Physics, University of Valencia, Burjassot 46100 (Spain)] [Department of Atomic, Molecular and Nuclear Physics, University of Valencia, Burjassot 46100 (Spain); Rivard, Mark J. [Department of Radiation Oncology, Tufts University School of Medicine, Boston, Massachusetts 02111 (United States)] [Department of Radiation Oncology, Tufts University School of Medicine, Boston, Massachusetts 02111 (United States)

    2014-02-15T23:59:59.000Z

    Purpose: In skin high-dose-rate (HDR) brachytherapy, sources are located outside, in contact with, or implanted at some depth below the skin surface. Most treatment planning systems use the TG-43 formalism, which is based on single-source dose superposition within an infinite water medium without accounting for the true geometry in which conditions for scattered radiation are altered by the presence of air. The purpose of this study is to evaluate the dosimetric limitations of the TG-43 formalism in HDR skin brachytherapy and the potential clinical impact. Methods: Dose rate distributions of typical configurations used in skin brachytherapy were obtained: a 5 cm × 5 cm superficial mould; a source inside a catheter located at the skin surface with and without backscatter bolus; and a typical interstitial implant consisting of an HDR source in a catheter located at a depth of 0.5 cm. Commercially available HDR{sup 60}Co and {sup 192}Ir sources and a hypothetical {sup 169}Yb source were considered. The Geant4 Monte Carlo radiation transport code was used to estimate dose rate distributions for the configurations considered. These results were then compared to those obtained with the TG-43 dose calculation formalism. In particular, the influence of adding bolus material over the implant was studied. Results: For a 5 cm × 5 cm{sup 192}Ir superficial mould and 0.5 cm prescription depth, dose differences in comparison to the TG-43 method were about ?3%. When the source was positioned at the skin surface, dose differences were smaller than ?1% for {sup 60}Co and {sup 192}Ir, yet ?3% for {sup 169}Yb. For the interstitial implant, dose differences at the skin surface were ?7% for {sup 60}Co, ?0.6% for {sup 192}Ir, and ?2.5% for {sup 169}Yb. Conclusions: This study indicates the following: (i) for the superficial mould, no bolus is needed; (ii) when the source is in contact with the skin surface, no bolus is needed for either {sup 60}Co and {sup 192}Ir. For lower energy radionuclides like {sup 169}Yb, bolus may be needed; and (iii) for the interstitial case, at least a 0.1 cm bolus is advised for {sup 60}Co to avoid underdosing superficial target layers. For {sup 192}Ir and {sup 169}Yb, no bolus is needed. For those cases where no bolus is needed, its use might be detrimental as the lack of radiation scatter may be beneficial to the patient, although the 2% tolerance for dose calculation accuracy recommended in the AAPM TG-56 report is not fulfilled.

  15. Plasmacytoid Dendritic Cells Capture and Cross-Present Viral Antigens from Influenza-Virus Exposed Cells

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    , France Abstract Among the different subsets of dendritic cells (DC), plasmacytoid dendritic cells (PDC, with human primary blood PDC and with a PDC cell line, that PDC display poor endocytic capacity for soluble or cellular antigens when compared to monocyte-derived myeloid DC. However, immature PDC efficiently take up

  16. Mutation assays involving blood cells that metabolize toxic substances

    DOE Patents [OSTI]

    Crespi, Charles L. (Downers Grove, IL); Thilly, William G. (Winchester, MA)

    1985-01-01T23:59:59.000Z

    A line of human blood cells which have high levels of oxidative activity (such as oxygenase, oxidase, peroxidase, and hydroxylase activity) is disclosed. Such cells grow in suspension culture, and are useful to determine the mutagenicity of xenobiotic substances that are metabolized into toxic or mutagenic substances. Mutation assays using these cells, and other cells with similar characteristics, are also disclosed.

  17. New Electronic Sensors Stick to Your Skin -Heart Rate Monitors -Popular Mechanics http://www.popularmechanics.com/science/health/breakthroughs/new-electronic-sensors-stick-to-your-skin?click=pm_latest[8/14/2011 5:59:45 AM

    E-Print Network [OSTI]

    Rogers, John A.

    New Electronic Sensors Stick to Your Skin - Heart Rate Monitors - Popular Mechanics http://www Electronic Sensors That Stick to Your Skin Like Temporary Tattoos Nice tattoo. Or is it a heart-rate monitor to measure the electrical activity of the heart, muscles and brain. And using the same principles behind

  18. Fuel Cells

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Fuel Cells Converting chemical energy of hydrogenated fuels into electricity Project Description Invented in 1839, fuels cells powered the Gemini and Apollo space missions, as well...

  19. Host-defense peptides isolated from the skin secretions of the Northern red-legged frog Rana aurora aurora

    E-Print Network [OSTI]

    Davidson, Carlos

    Host-defense peptides isolated from the skin secretions of the Northern red-legged frog Rana aurora aurora J. Michael Conlona,*, Agnes Sonnevendb , Carlos Davidsonc , Anni Demandtd , Thierry Jouennee-stimulated skin secretions of the Northern red-legged frog Rana aurora aurora and their primary structures

  20. Evidence from peptidomic analysis of skin secretions that the red-legged frogs, Rana aurora draytonii and

    E-Print Network [OSTI]

    Davidson, Carlos

    Evidence from peptidomic analysis of skin secretions that the red-legged frogs, Rana aurora draytonii and Rana aurora aurora, are distinct species J. Michael Conlon a, *, Nadia Al-Ghafari a , Laurent peptides Rana aurora Rana draytonii Skin secretions a b s t r a c t The northern red-legged frog Rana

  1. NON-MELANOMA SKIN LESION CLASSIFICATION USING COLOUR IMAGE DATA IN A HIERARCHICAL K-NN CLASSIFIER

    E-Print Network [OSTI]

    Fisher, Bob

    NON-MELANOMA SKIN LESION CLASSIFICATION USING COLOUR IMAGE DATA IN A HIERARCHICAL K-NN CLASSIFIER an algorithm for classification of non- melanoma skin lesions based on a novel hierarchical K- Nearest lesions, including two non-melanoma cancer types. This is the most extensive published result on non-melanoma

  2. A Prospective Study of Blood Selenium Levels and the Risk of Arsenic-2 related Premalignant Skin Lesions3

    E-Print Network [OSTI]

    van Geen, Alexander

    1 1 A Prospective Study of Blood Selenium Levels and the Risk of Arsenic-2 related Premalignant-related premalignant skin lesions and prediagnostic blood Se levels in 30357 cases of skin lesions newly-diagnosed from in the Health Effects59 of As Longitudinal Study with available baseline blood and urine samples collected in60

  3. A numerical study of the effects of superhydrophobic surface on skin-friction drag in turbulent channel flow

    E-Print Network [OSTI]

    Kim, John

    A numerical study of the effects of superhydrophobic surface on skin- friction drag in turbulent;PHYSICS OF FLUIDS 25, 110815 (2013) A numerical study of the effects of superhydrophobic surface on skin; accepted 21 May 2013; published online 11 September 2013) Superhydrophobic surfaces have attracted much

  4. ON THE INFLUENCE OF THE GEOMETRY ON SKIN EFFECT IN ELECTROMAGNETISM

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    ON THE INFLUENCE OF THE GEOMETRY ON SKIN EFFECT IN ELECTROMAGNETISM GABRIEL CALOZ, MONIQUE DAUGE) 1053-1068" DOI : 10.1016/j.cma.2010.11.011 #12;2 GABRIEL CALOZ, MONIQUE DAUGE, ERWAN FAOU, VICTOR P of the conducting body surface is larger ­ and here the sign of the curvature has a major influence, which means

  5. Density slope of the nuclear symmetry energy from the neutron skin thickness of heavy nuclei

    E-Print Network [OSTI]

    Chen, Lie-Wen; Ko, Che Ming; Li, Bao-An; Xu, Jun.

    2010-01-01T23:59:59.000Z

    of finite nuclei and nuclear matter properties. We find that existing data on neutron skin thickness Delta r(np) of Sn isotopes give an important constraint on the symmetry energy E(sym)(rho(0)) and its density slope L at saturation density rho(0). Combining...

  6. HEAT TRANSFERS IN A DOUBLE SKIN ROOF VENTILATED BY NATURAL CONVECTION IN SUMMER TIME

    E-Print Network [OSTI]

    Boyer, Edmond

    1 HEAT TRANSFERS IN A DOUBLE SKIN ROOF VENTILATED BY NATURAL CONVECTION IN SUMMER TIME P. H and the sheet metal: This is ventilation by natural convection. The remaining conductive heat from the sheet or in tropical and arid countries. In this work, radiation, convection and conduction heat transfers

  7. Evaluation and design of double-skin facades for office buildings in hot climates

    E-Print Network [OSTI]

    Yellamraju, Vijaya

    2004-09-30T23:59:59.000Z

    efficient strategy and also the factors that affected this efficiency. The simulations were done using the building simulation software, Ener-Win. The double skin was simulated as per an approximate and simplistic calculation of the u-value, solar heat gain...

  8. Exact volume preserving skinning with shape control Damien Rohmer1,2

    E-Print Network [OSTI]

    skinning, perfectly fits into the usual production pipeline. It can be used whatever the desired locality the way rubber-like materials and organic shapes respectively deform can be modeled. An improved algorithm is a complex process, which needs to fit into the standard production pipe-line for efficient use by artists

  9. Early detection of malignant skin can-cers, in particular melanoma, is crucial as

    E-Print Network [OSTI]

    Drew, Mark S.

    MOTIVATION · Early detection of malignant skin can- cers, in particular melanoma, is crucial). EXPERIMENTS AND RESULTS Melanoma Melanin Haemoglobin Geo­mean BCC Spits Nevus Task n Precision Recall F-measure AUC Segmentation 120 0.89 0.90 0.89 ­ Malignant vs. Benign 500 0.89 0.89 0.89 0.95 Melanoma vs. Benign

  10. Original Paper Skin Self-Examination Education for Early Detection of Melanoma

    E-Print Network [OSTI]

    Chisholm, Rex L.

    Original Paper Skin Self-Examination Education for Early Detection of Melanoma: A Randomized Background: Early detection of melanoma improves survival. Since many melanoma patients and their spouses seek the care of a physician after discovering their melanoma, an ongoing study will determine

  11. Three-dimensional imaging of skin melanoma in vivo by dual-wavelength photoacoustic microscopy

    E-Print Network [OSTI]

    Wang, Lihong

    Three-dimensional imaging of skin melanoma in vivo by dual-wavelength photoacoustic microscopy Jung to noninvasively obtain three-dimensional 3-D images of subcutaneous melanomas and their surrounding vasculature in nude mice in vivo. The absorption coefficients of blood and melanin- pigmented melanomas vary greatly

  12. INTRODUCTION Skin temperature (ST) retrievals are currently made every hour from 1145 to

    E-Print Network [OSTI]

    Haines, Stephanie L.

    temperature measurements are an important input for operational meteorology applications such as model). Land skin temperature measurements have important applications in agriculture including frost detection of the urban heat island effect (Hafner and Kidder 1999; Lo et al. 1997) and the study of the earth's energy

  13. Water skin anomalies: density, elasticity, hydrophobicity, thermal stability, interface repulsivity, etc

    E-Print Network [OSTI]

    Chang Q. Sun

    2015-02-26T23:59:59.000Z

    Molecular undercoordination induced O:H-O bond relaxation and dual polarization dictates the supersolid behavior of water skins interacting with other substances such as flowing in nanochannels, dancing of water droplets, floating of insects. The BOLS-NEP notion unifies the Wenzel-Cassie-Baxter models and explains controllable transition between hydrophobicity and hydrophilicity.

  14. Detection of blood deprived regions in SIAgraph images of pigmented skin lesions

    E-Print Network [OSTI]

    Claridge, Ela

    Detection of blood deprived regions in SIAgraph images of pigmented skin lesions Francesca Sattaa for the diagnosis of malignant melanoma has shown that the presence of blood deprivation regions within the lesion of the blood deprived regions. The results of the computer method compared to the clinical assessment show very

  15. Have we observed the skin vibration of realistic strange stars (ReSS) ?

    E-Print Network [OSTI]

    Monika Sinha; Jishnu Dey; Mira Dey; Subharthi Ray; Siddhartha Bhowmick

    2002-11-27T23:59:59.000Z

    Skin vibration of ReSS and consequent resonance absorption can account for the absorption lines in the spectrum of X-ray emission from many compact stellar objects and in particular, the stars J1210$-$5226 and RXJ1856$-$3754. Observations of the X-ray spectrum of these stars is difficult to explain, if they are neutron stars.

  16. Human-machine interactions

    DOE Patents [OSTI]

    Forsythe, J. Chris (Sandia Park, NM); Xavier, Patrick G. (Albuquerque, NM); Abbott, Robert G. (Albuquerque, NM); Brannon, Nathan G. (Albuquerque, NM); Bernard, Michael L. (Tijeras, NM); Speed, Ann E. (Albuquerque, NM)

    2009-04-28T23:59:59.000Z

    Digital technology utilizing a cognitive model based on human naturalistic decision-making processes, including pattern recognition and episodic memory, can reduce the dependency of human-machine interactions on the abilities of a human user and can enable a machine to more closely emulate human-like responses. Such a cognitive model can enable digital technology to use cognitive capacities fundamental to human-like communication and cooperation to interact with humans.

  17. Cancer Res . Author manuscript Spleen tyrosine kinase functions as a tumor suppressor in melanoma cells

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    in melanoma cells by inducing senescence-like growth arrest Olivier Bailet 1 , Nina Fenouille 1 , Patricia that has been recently implicated in tumor suppression of melanoma, a deadly skin cancer deriving from pigments-producing melanocytes. However, the mechanism by which Syk suppresses melanoma growth remains

  18. Structural studies of the human polymeric immunoglobulin receptor

    E-Print Network [OSTI]

    Hamburger, Agnes Eva, 1976-

    2005-01-01T23:59:59.000Z

    The human polymeric immunoglobulin receptor, pIgR, is a glycosylated type I transmembrane protein expressed on the basolateral surface of secretory epithelial cells. pIgR plays a key role in mucosal immunity and, together ...

  19. Transport Pathways and Enhancement Mechanisms within Localized and Non-Localized Transport Regions in Skin Treated with Low-Frequency Sonophoresis and Sodium Lauryl Sulfate

    E-Print Network [OSTI]

    Polat, Baris E.

    Recent advances in transdermal drug delivery utilizing low-frequency sonophoresis (LFS) and sodium lauryl sulfate (SLS) have revealed that skin permeability enhancement is not homogenous across the skin surface. Instead, ...

  20. 1622 JOURNAL OF MICROELECTROMECHANICAL SYSTEMS, VOL. 15, NO. 6, DECEMBER 2006 Skin-Effect Self-Heating in Air-Suspended RF

    E-Print Network [OSTI]

    Saitou, Kazuhiro "Kazu"

    1622 JOURNAL OF MICROELECTROMECHANICAL SYSTEMS, VOL. 15, NO. 6, DECEMBER 2006 Skin-Effect Self-Heating

  1. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    SciTech Connect (OSTI)

    Tamura, Akitoshi, E-mail: akitoshi-tamura@ds-pharma.co.jp; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-08-15T23:59:59.000Z

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased inflammatory cells and IgE, but the others did not. • The allergic drugs commonly induced germinal center hyperplasia in lymphoid tissues. • Some of these allergic drugs transiently increased CD4{sup +}CD25{sup +} T cells in the spleen.

  2. Absorbed dose in target cell nuclei and dose conversion coefficient of radon progeny

    E-Print Network [OSTI]

    Yu, K.N.

    Absorbed dose in target cell nuclei and dose conversion coefficient of radon progeny in the human Abstract To calculate the absorbed dose in the human lung due to inhaled radon progeny, ICRP focussed and secretory cells). The absorbed energy for alpha particles emitted by radon progeny in the human respiratory

  3. Breast Cancer Cells Induce Cancer-Associated Fibroblasts to Secrete Hepatocyte Growth Factor to Enhance Breast Tumorigenesis

    E-Print Network [OSTI]

    2011-01-01T23:59:59.000Z

    fetal bovine serum and 1610 5 MDA-MB-468 cells were seededwith human breast cancer MDA-MB-468 cells in a transwellNAFs with breast cancer MDA-MB-468 cells in a transwell

  4. Asymmetric cancer cell division regulated by AKT Ipsita Dey-Guhaa,b,1

    E-Print Network [OSTI]

    Albeck, John

    Cancer Cells in Vitro. We began by studying MCF7, a highly proliferative, aneuploid, ER+ /HER2- human that slowly pro- liferating MCF7 cells might produce low levels of reactive oxygen species (ROS stem cells and cancer stem cells produce low levels of ROS (5­7). We stained MCF7 cells with 5-(and-6

  5. Proliferative and toxic effects of ultraviolet light and inflammation on epidermal pigment cells

    SciTech Connect (OSTI)

    Nordlund, J.J.; Ackles, A.E.; Traynor, F.F.

    1981-10-01T23:59:59.000Z

    The ear of the mouse is useful for studying the effects of ultraviolet light on epidermal pigment cells. The quantity of light penetrating into the skin causing an inflammatory response can be assessed easily by measuring with an engineering calipers the swelling of the ear. The inflammatory response of the ear exhibits a linear relationship to the dose of light delivered. We observed that doses of shortwave ultraviolet light which are noninflammatory when repeated at daily intervals induce moderate to severe inflammation. Small doses of psoralen and prolonged exposure to UVA (PUVA) were more inflammatory than larger amounts of psoralen and short exposure to light. Doses of shortwave ultraviolet light and PUVA which produce only a minimal inflammation of the skin stimulate the proliferation of epidermal melanocytes. In contrast, PUVA in doses sufficiently large to cause a marked inflammatory reaction in the skin seems injurious to pigment cells and kills them or causes only a minimal proliferative response. The inflammatory reaction itself does not seem to stimulate or inhibit the proliferation of melanocytes. Prostaglandins A, E, and F2 alpha have no effect on the proliferation of epidermal pigment cells. In contrast, dimethyl sulfoxide (DMSO) and allergic contact dermatitis increase the numerical density of pigment cells. Steroids may block the function of the enzyme tyrosinase. Our experiments indicate that pigment cells, like many other varieties of cells, are susceptible to injury and can be killed at least by large doses of PUVA.

  6. RESEARCH ARTICLE Open Access Vaccination with human anti-trastuzumab

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    viability of SK-OV-3 cells, a HER2-positive cancer cell line, in nude mice. MMTV.f.huHER2(Fo5) transgenicRESEARCH ARTICLE Open Access Vaccination with human anti-trastuzumab anti-idiotype scFv reverses relapses in HER2-expressing breast cancer. Here, we tested whether trastuzumab-selected single-chain Fv (sc

  7. Anomalous skin effects in relativistic parallel propagating weakly magnetized electron plasma waves

    SciTech Connect (OSTI)

    Abbas, Gohar; Bashir, M. F. [Salam Chair in Physics, G. C. University, Lahore 54000 (Pakistan); Department of Physics, G. C. University, Lahore 54000 (Pakistan); Murtaza, G. [Salam Chair in Physics, G. C. University, Lahore 54000 (Pakistan)

    2011-10-15T23:59:59.000Z

    Fully relativistic analysis of anomalous skin effects for parallel propagating waves in a weakly magnetized electron plasma is presented and general expressions for longitudinal and transverse permittivites are derived. It is found that the penetration depth for R- and L-waves increases as we move from non-relativistic to highly relativistic regime. The ambient magnetic field reduces/enhances the skin effects for R-wave/L-wave as the strength of the field is increased. In general, the weak magnetic field effects are pronounced for the weakly relativistic regime as compared with other relativistic cases. The results are also graphically illustrated. On switching off the magnetic field, previous results for field free case are retrieved [A. F. Alexandrov, A. S. Bogdankevich, and A. A. Rukhadze, Priniples of Plasma Electrodynamics (Springer-Verlag, Berlin, Heidelberg, 1984), Vol. 9, p. 106].

  8. Heat transfers in a double-skin roof ventilated by natural convection in summer time

    E-Print Network [OSTI]

    Biwole, Pascal; Pompeo, C

    2013-01-01T23:59:59.000Z

    The double-skin roofs investigated in this paper are formed by adding a metallic screen on an existing sheet metal roof. The system enhances passive cooling of dwellings and can help diminishing power costs for air conditioning in summer or in tropical and arid countries. In this work, radiation, convection and conduction heat transfers are investigated. Depending on its surface properties, the screen reflects a large amount of oncoming solar radiation. Natural convection in the channel underneath drives off the residual heat. The bi-dimensional numerical simulation of the heat transfers through the double skin reveals the most important parameters for the system's efficiency. They are, by order of importance, the sheet metal surface emissivity, the screen internal and external surface emissivity, the insulation thickness and the inclination angle for a channel width over 6 cm. The influence of those parameters on Rayleigh and Nusselt numbers is also investigated. Temperature and air velocity profiles on seve...

  9. Dose profiles through the dermis for on and off-skin hot particle exposures 

    E-Print Network [OSTI]

    Shaw, Kimberly Rochelle

    1993-01-01T23:59:59.000Z

    reports measurements of depth-dose profiles for on- and off-skin hot particle exposures using radiochromic dye film. Dose profiles from both a "Co hot particle, and activated depleted uranium oxide microspheres were measured with the film. Exposures... Page Off-Contact of Film 13. ' Co Dose Profile Measured with 6 mm Thick Plexiglass Between Film and Hot Particle 48 14. Radial Dose Profile of Uranium Microsphere Measured at Various Depths Below the Sphere 51 15. Dose Profile of Uranium...

  10. THERMAL SKIN DAMAGE AND MOBILE PHONE USE Elmountacer Billah Elabbassi(1)

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    in thé phone by thé battery currents and running of thé radiofrequency (RF) electronic circuits measured thé température of thé temporal skin due to GSM 1800 MHz MP radiated power (125 mW). To perforai a substantial part of thé radiated power is absorbed. Many epidemiological investigations of MP users [1, 2

  11. An evaluation of floor surfaces on the basis of skin temperature during constrained standing

    E-Print Network [OSTI]

    Monford, Leo Gabriel

    1995-01-01T23:59:59.000Z

    popliteal fossa (popliteal region), and the medial side of abductor hallucis on the non-load bearing region of the foot (near the intersection of the top of the arch and the instep) or the foot region. All thermistors were located on the left leg... between an average ending temperature and an average start-up temperature. The foot skin temperature region was the only temperature region to indicate statistically significant results between the floor surfaces. The other two lower leg temperature...

  12. Mesenchymal Stem Cells Retain Their Defining Stem Cell Characteristics After Exposure to Ionizing Radiation

    SciTech Connect (OSTI)

    Nicolay, Nils H., E-mail: n.nicolay@dkfz.de [Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg (Germany); Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg (Germany); Sommer, Eva; Lopez, Ramon; Wirkner, Ute [Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg (Germany); Trinh, Thuy [Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg (Germany); Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg (Germany); Sisombath, Sonevisay [Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg (Germany); Debus, Jürgen [Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg (Germany); Ho, Anthony D.; Saffrich, Rainer [Department of Hematology and Oncology, Heidelberg University Hospital, Heidelberg (Germany); Huber, Peter E. [Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg (Germany); Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg (Germany)

    2013-12-01T23:59:59.000Z

    Purpose: Mesenchymal stem cells (MSCs) have the ability to migrate to lesion sites and undergo differentiation into functional tissues. Although this function may be important for tissue regeneration after radiation therapy, the influence of ionizing radiation (IR) on cellular survival and the functional aspects of differentiation and stem cell characteristics of MSCs have remained largely unknown. Methods and Materials: Radiation sensitivity of human primary MSCs from healthy volunteers and primary human fibroblast cells was examined, and cellular morphology, cell cycle effects, apoptosis, and differentiation potential after exposure to IR were assessed. Stem cell gene expression patterns after exposure to IR were studied using gene arrays. Results: MSCs were not more radiosensitive than human primary fibroblasts, whereas there were considerable differences regarding radiation sensitivity within individual MSCs. Cellular morphology, cytoskeletal architecture, and cell motility were not markedly altered by IR. Even after high radiation doses up to 10 Gy, MSCs maintained their differentiation potential. Compared to primary fibroblast cells, MSCs did not show an increase in irradiation-induced apoptosis. Gene expression analyses revealed an upregulation of various genes involved in DNA damage response and DNA repair, but expression of established MSC surface markers appeared only marginally influenced by IR. Conclusions: These data suggest that human MSCs are not more radiosensitive than differentiated primary fibroblasts. In addition, upon photon irradiation, MSCs were able to retain their defining stem cell characteristics both on a functional level and regarding stem cell marker expression.

  13. Neutron-skin thickness from the study of the anti-analog giant dipole resonance

    E-Print Network [OSTI]

    A. Krasznahorkay; L. Stuhl; M. Csatlós; A. Algora; J. Gulyás; J. Timár; N. Paar; D. Vretenar; K. Boretzky; M. Heil; Yu. A. Litvinov; D. Rossi; C. Scheidenberger; H. Simon; H. Weick; A. Bracco; S. Brambilla; N. Blasi; F. Camera; A. Giaz; B. Million; L. Pellegri; S. Riboldi; O. Wieland; S. Altstadt; M. Fonseca; J. Glorius; K. Göbel; T. Heftrich; A. Koloczek; S. Kräckmann; C. Langer; R. Plag; M. Pohl; G. Rastrepina; R. Reifarth; S. Schmidt; K. Sonnabend; M. Weigand; M. N. Harakeh; N. Kalantar-Nayestanaki; C. Rigollet; S. Bagchi; M. A. Najafi; T. Aumann; L. Atar; M. Heine; M. Holl; A. Movsesyan; P. Schrock; V. Volkov; F. Wamers; E. Fiori; B. Löher; J. Marganiec; D. Savran; H. T. Johansson; P. Diaz Fernández; U. Garg; D. L. Balabanski

    2012-06-20T23:59:59.000Z

    The gamma-decay of the anti-analog of the giant dipole resonance (AGDR) has been measured to the isobaric analog state excited in the p(124Sn,n) reaction at a beam energy of 600 MeV/nucleon. The energy of the transition was also calculated with state-of-the-art self-consistent random-phase approximation (RPA) and turned out to be very sensitive to the neutron-skin thickness (\\DeltaR_(pn)). By comparing the theoretical results with the measured one, the \\DeltaR_(pn) value for 124Sn was deduced to be 0.175 \\pm 0.048 fm, which agrees well with the previous results. The energy of the AGDR measured previously for ^(208)Pb was also used to determine the \\DeltaR_(pn) for ^(208)Pb. In this way a very precise \\DeltaR_(pn) = 0.181 \\pm 0.031 neutron-skin thickness has been obtained for 208Pb. The present method offers new possibilities for measuring the neutron-skin thicknesses of very exotic isotopes.

  14. Effect of dietary polyunsaturated fatty acids and related nutrients on sebum lipids, and skin and hair coat condition in canines 

    E-Print Network [OSTI]

    Kirby, Naomi Anne

    2005-02-17T23:59:59.000Z

    A study was performed to investigate the effect of diets rich in polyunsaturated fatty acids and other related nutrients, in the effort to improve skin and hair coat conditions in canines. The study included 24 dogs fed a ...

  15. Investigation of Skin Tribology and Its Effects on Coefficient of Friction and Other Tactile Attributes Involving Polymer Applications 

    E-Print Network [OSTI]

    Darden, Matthew Aguirre

    2012-02-14T23:59:59.000Z

    concerning tactility, examining environmental and material properties that affect skin on fabric coefficient of friction. In this study, similar friction procedure was used to compare coefficients of friction of a fingerpad across varying polymer fabrics...

  16. Technical Note: Skin thickness measurements using high-resolution flat-panel cone-beam dedicated breast CT

    SciTech Connect (OSTI)

    Shi Linxi; Vedantham, Srinivasan; Karellas, Andrew [Department of Radiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655 (United States); O'Connell, Avice M. [Department of Radiology, University of Rochester Medical Center, Rochester, New York 14642 (United States)

    2013-03-15T23:59:59.000Z

    Purpose: To determine the mean and range of location-averaged breast skin thickness using high-resolution dedicated breast CT for use in Monte Carlo-based estimation of normalized glandular dose coefficients. Methods: This study retrospectively analyzed image data from a clinical study investigating dedicated breast CT. An algorithm similar to that described by Huang et al.['The effect of skin thickness determined using breast CT on mammographic dosimetry,' Med. Phys. 35(4), 1199-1206 (2008)] was used to determine the skin thickness in 137 dedicated breast CT volumes from 136 women. The location-averaged mean breast skin thickness for each breast was estimated and the study population mean and range were determined. Pathology results were available for 132 women, and were used to investigate if the distribution of location-averaged mean breast skin thickness varied with pathology. The effect of surface fitting to account for breast curvature was also studied. Results: The study mean ({+-} interbreast SD) for breast skin thickness was 1.44 {+-} 0.25 mm (range: 0.87-2.34 mm), which was in excellent agreement with Huang et al. Based on pathology, pair-wise statistical analysis (Mann-Whitney test) indicated that at the 0.05 significance level, there were no significant difference in the location-averaged mean breast skin thickness distributions between the groups: benign vs malignant (p= 0.223), benign vs hyperplasia (p= 0.651), hyperplasia vs malignant (p= 0.229), and malignant vs nonmalignant (p= 0.172). Conclusions: Considering this study used a different clinical prototype system, and the study participants were from a different geographical location, the observed agreement between the two studies suggests that the choice of 1.45 mm thick skin layer comprising the epidermis and the dermis for breast dosimetry is appropriate. While some benign and malignant conditions could cause skin thickening, in this study cohort the location-averaged mean breast skin thickness distributions did not differ significantly with pathology. The study also underscored the importance of considering breast curvature in estimating breast skin thickness.

  17. Relationships among antioxidants, phenolics, and specific gravity in potato cultivars, and evaluation of wild potato species for antioxidants, glycoalkaloids, and anti-cancer activity on human prostate and colon cancer cells in vitro.

    E-Print Network [OSTI]

    Nzaramba, Magnifique Ndambe

    2009-05-15T23:59:59.000Z

    and significance of cultivar, location, year, and interaction effects for antioxidant activity, phenolic content, and specific gravity of four potato cultivars grown in five locations during the 2005, 2006, and 2007 growing seasons...; Giovannelli et al., 2000; Rodriguez et al., 2007; Shahidi, 2002), modulation of detoxifying enzymes, stimulation of the immune system, regulation of cell proliferation and apoptosis (Kern et al., 2007; Kim et al., 2006; Reddivari et al., 2007b...

  18. Method for restoration of normal phenotype in cancer cells

    DOE Patents [OSTI]

    Bissell, Mina J. (Berkeley, CA); Weaver, Valerie M. (Oakland, CA)

    2000-01-01T23:59:59.000Z

    A method for reversing expression of malignant phenotype in cancer cells is described. The method comprises applying .beta..sub.1 integrin function-blocking antibody to the cells. The method can be used to assess the progress of cancer therapy. Human breast epithelial cells were shown to be particularly responsive.

  19. Red Blood Cell Segmentation from SEM Images Joost Vromen

    E-Print Network [OSTI]

    McCane, Brendan

    Red Blood Cell Segmentation from SEM Images Joost Vromen Human Media Interaction University Microscope image of red blood cells. We use a second order polynomial model and a simple Bayesian approach sample images involving more than 11000 red blood cells. I. INTRODUCTION There is considerable evidence

  20. Chemical Biology Chemical Screening for Hair Cell Loss and Protection

    E-Print Network [OSTI]

    Rubel, Edwin

    Chemical Biology Chemical Screening for Hair Cell Loss and Protection in the Zebrafish Lateral Line Rubel,1,2 and David W. Raible1,4 Abstract In humans, most hearing loss results from death of hair cells, the mechanosensory receptors of the inner ear. Two goals of current hearing research are to protect hair cells from

  1. Human Resources Assistant

    Broader source: Energy.gov [DOE]

    This position is located in the Headquarters (HQ) Operations Division of the Office of the Chief Human Capital Officer in Washington, DC. The Division provides a full range of human capital...

  2. Patenting Human Evolution

    E-Print Network [OSTI]

    Torrance, Andrew W.

    2008-06-01T23:59:59.000Z

    to thorough analysis and debate prior to the imminent arrival of human genetic enhancement technologies. Otherwise, patent law may drive human evolution in directions either unplanned - or worse - undesired....

  3. Human Functional Brain Imaging

    E-Print Network [OSTI]

    Rambaut, Andrew

    Human Functional Brain Imaging 1990­2009 September 2011 Portfolio Review #12;2 | Portfolio Review: Human Functional Brain ImagingThe Wellcome Trust is a charity registered in England and Wales, no's role in supporting human functional brain imaging and have informed `our' speculations for the future

  4. integration division Human Systems

    E-Print Network [OSTI]

    integration division Human Systems Eye-Movement Metrics: Non-Intrusive Quantitative Tools for Monitoring Human Visual Performance Objective Approach Impact A reliable quantitative yet non-intrusive methodologies that provide quantitative yet non-intrusive measures of human visual performance for use

  5. Health burden of skin lesions at low arsenic exposure through groundwater in Pakistan. Is river the source?

    SciTech Connect (OSTI)

    Fatmi, Zafar, E-mail: zafar.fatmi@aku.edu [Department of Community Health Sciences, Aga Khan University, Stadium Road, P.O. Box 3500, Karachi (Pakistan)] [Department of Community Health Sciences, Aga Khan University, Stadium Road, P.O. Box 3500, Karachi (Pakistan); Azam, Iqbal; Ahmed, Faiza; Kazi, Ambreen; Gill, Albert Bruce; Kadir, Muhmmad Masood; Ahmed, Mubashir; Ara, Naseem; Janjua, Naveed Zafar [Department of Community Health Sciences, Aga Khan University, Stadium Road, P.O. Box 3500, Karachi (Pakistan)] [Department of Community Health Sciences, Aga Khan University, Stadium Road, P.O. Box 3500, Karachi (Pakistan)

    2009-07-15T23:59:59.000Z

    A significant proportion of groundwater in south Asia is contaminated with arsenic. Pakistan has low levels of arsenic in groundwater compared with China, Bangladesh and India. A representative multi-stage cluster survey conducted among 3874 persons {>=}15 years of age to determine the prevalence of arsenic skin lesions, its relation with arsenic levels and cumulative arsenic dose in drinking water in a rural district (population: 1.82 million) in Pakistan. Spot-urine arsenic levels were compared among individuals with and without arsenic skin lesions. In addition, the relation of age, body mass index, smoking status with arsenic skin lesions was determined. The geographical distribution of the skin lesions and arsenic-contaminated wells in the district were ascertained using global positioning system. The total arsenic, inorganic and organic forms, in water and spot-urine samples were determined by atomic absorption spectrophotometry. The prevalence of skin lesions of arsenic was estimated for complex survey design, using surveyfreq and surveylogistic options of SAS 9.1 software.The prevalence of definitive cases i.e. hyperkeratosis of both palms and soles, was 3.4 per 1000 and suspected cases i.e. any sign of arsenic skin lesions (melanosis and/or keratosis), were 13.0 per 1000 among {>=}15-year-old persons in the district. Cumulative arsenic exposure (dose) was calculated from levels of arsenic in water and duration of use of current drinking water source. Prevalence of skin lesions increases with cumulative arsenic exposure (dose) in drinking water and arsenic levels in urine. Skin lesions were 2.5-fold among individuals with BMI <18.5 kg/m{sup 2}. Geographically, more arsenic-contaminated wells and skin lesions were alongside Indus River, suggests a strong link between arsenic contamination of groundwater with proximity to river.This is the first reported epidemiological and clinical evidence of arsenic skin lesions due to groundwater in Pakistan. Further investigations and focal mitigation measures for arsenic may be carried out alongside Indus River.

  6. Fuel Cells

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    the major national security imperatives of this century. Get Expertise Rod Borup MPA-11, Fuel Cell Program Manager Email Andrew Dattelbaum MPA-11 Group Leader Email Melissa Fox...

  7. acid-induced fibroblast cell: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    STUDY OF DNA DOUBLE-STRAND BREAKS IN BYSTANDER PRIMARY HUMAN FIBROBLASTS L. B. Smilenov-or-nothing manner(7) . Bystander cells exhibit a variety of characteristics of...

  8. Human Cementum Protein 1 induces expression of bone and cementum proteins by human gingival fibroblasts

    SciTech Connect (OSTI)

    Carmona-Rodriguez, Bruno [Laboratorio de Biologia Celular y Molecular, Facultad de Odontologia, UNAM, Cd. Universitaria, Coyoacan, Mexico, D.F. 04510 (Mexico); Alvarez-Perez, Marco Antonio [Laboratorio de Biologia Celular y Molecular, Facultad de Odontologia, UNAM, Cd. Universitaria, Coyoacan, Mexico, D.F. 04510 (Mexico); Narayanan, A. Sampath [Department of Pathology, School of Medicine, UW, Seattle (United States); Zeichner-David, Margarita [Center for Craniofacial Molecular Biology, School of Dentistry, USC, Los Angeles (United States); Reyes-Gasga, Jose [Instituto de Fisica, UNAM (Mexico); Molina-Guarneros, Juan [Facultad de Medicina, UNAM (Mexico); Garcia-Hernandez, Ana Lilia [Laboratorio de Biologia Celular y Molecular, Facultad de Odontologia, UNAM, Cd. Universitaria, Coyoacan, Mexico, D.F. 04510 (Mexico); Suarez-Franco, Jose Luis [Laboratorio de Biologia Celular y Molecular, Facultad de Odontologia, UNAM, Cd. Universitaria, Coyoacan, Mexico, D.F. 04510 (Mexico); Chavarria, Ivet Gil [Laboratorio de Biologia Celular y Molecular, Facultad de Odontologia, UNAM, Cd. Universitaria, Coyoacan, Mexico, D.F. 04510 (Mexico); Villarreal-Ramirez, Eduardo [Laboratorio de Biologia Celular y Molecular, Facultad de Odontologia, UNAM, Cd. Universitaria, Coyoacan, Mexico, D.F. 04510 (Mexico); Arzate, Higinio [Laboratorio de Biologia Celular y Molecular, Facultad de Odontologia, UNAM, Cd. Universitaria, Coyoacan, Mexico, D.F. 04510 (Mexico)]. E-mail: harzate@servidor.unam.mx

    2007-07-06T23:59:59.000Z

    We recently presented evidence showing that a human cementoblastoma-derived protein, named Cementum Protein 1 (CEMP1) may play a role as a local regulator of cementoblast differentiation and cementum-matrix mineralization. This protein was shown to be expressed by cementoblasts and progenitor cells localized in the periodontal ligament. In this study we demonstrate that transfection of CEMP1 into human gingival fibroblasts (HGF) induces mineralization and expression of bone and cementum-matrix proteins. The transfected HGF cells had higher alkaline phosphatase activity and proliferation rate and they expressed genes for alkaline phosphatase, bone sialoprotein, osteocalcin, osteopontin, the transcription factor Runx2/Cbfa1, and cementum attachment protein (CAP). They also produced biological-type hydroxyapatite. These findings indicate that the CEMP1 might participate in differentiation and mineralization of nonosteogenic cells, and that it might have a potential function in cementum and bone formation.

  9. The effect of Stromal cell Derived Factor-1 (SDF-1) and collagen-GAG (Glycosaminoglycan) scaffold on skin wound healing

    E-Print Network [OSTI]

    Sarkar, Aparajita

    2008-01-01T23:59:59.000Z

    Wound healing is an intricate biological process requiring the appropriate balance of matrix and growth factors. Apart from causing physical deformity, adult wound healing results in the formation of scar tissue, which can ...

  10. E4F1 is essential for epidermal stem cell maintenance and skin homeostasis Matthieu Lacroix1, 3, 4, 10, &

    E-Print Network [OSTI]

    Boyer, Edmond

    of Sciences of the United States of America 2010;107 (49):21076-81" DOI : 10.1073/pnas.1010167107 #12

  11. Mechanical stiffness-defined matrices for stem cell research and drug screening

    E-Print Network [OSTI]

    Ha, Vu Nguyen Tuan

    2008-01-01T23:59:59.000Z

    Synthetic polymer matrices or subtrata with tailored elastic properties provide a powerful method to direct biological cell' differentiation and foster cell multiplication. By changing the stiffness of the substrate, human ...

  12. The effect of weightlessness on cytoskeleton architecture and proliferation of human breast

    E-Print Network [OSTI]

    Portet, Stéphanie

    was kept in a 1g centrifuge (1g in-flight control). Human breast cancer cells MCF-7, flown in space launching), cells were more fully spread in 1g in-flight control than in g. The fraction of cycling MCF-7. Finally, MCF-7 cell proliferation was reduced in g. 3. Some MCF-7 clusters showed altered microtubules (MT

  13. Dose profiles through the dermis for on and off-skin hot particle exposures

    E-Print Network [OSTI]

    Shaw, Kimberly Rochelle

    1993-01-01T23:59:59.000Z

    compared to gamma-rays. Gamma-rays are monoenergetic photons with energies ranging from a few keV to several MeV. Unlike beta particles, gamma-rays are indirectly ionizing radiation. Because a gamma-ray is uncharged, it undergoes no direct ionization... detailed data on dose profiles This thesis follows the format of Radiation Protection Dosimetry. through the dermis from fuel fragments or from mixed beta-gamma activation products. The effects of beta-emitting hot particles suspended above skin without...

  14. Constraining the symmetry energy from the neutron skin thickness of Tin isotopes

    E-Print Network [OSTI]

    Lie-Wen Chen; Che Ming Ko; Jun Xu; Bao-An Li

    2011-03-24T23:59:59.000Z

    We show in the Skyrme-Hartree-Fock approach that unambiguous correlations exist between observables of finite nuclei and nuclear matter properties. Using this correlation analysis to existing data on the neutron skin thickness of Sn isotopes, we find important constraints on the value E_{sym}(rho_0) and density slope L of the nuclear symmetry energy at saturation density. Combining these constraints with those from recent analyses of isospin diffusion and double neutron/proton ratio in heavy ion collisions leads to a value of L=58\\pm 18 MeV approximately independent of E_{sym}(\\rho_0).

  15. Mutation assays involving blood cells that metabolize toxic substances

    DOE Patents [OSTI]

    Crespi, C.L.; Thilly, W.G.

    1999-08-10T23:59:59.000Z

    The present invention pertains to a line of human blood cells which have high levels of oxidative activity (such as oxygenase, oxidase, peroxidase, and hydroxylase activity). Such cells grow in suspension culture, and are useful to determine the mutagenicity of xenobiotic substances that are metabolized into toxic or mutagenic substances. The invention also includes mutation assays using these cells, and other cells with similar characteristics. 3 figs.

  16. Mutation assays involving blood cells that metabolize toxic substances

    DOE Patents [OSTI]

    Crespi, Charles L. (Marblehead, MA); Thilly, William G. (Winchester, MA)

    1999-01-01T23:59:59.000Z

    The present invention pertains to a line of human blood cells which have high levels of oxidative activity (such as oxygenase, oxidase, peroxidase, and hydroxylase activity). Such cells grow in suspension culture, and are useful to determine the mutagenicity of xenobiotic substances that are metabolized into toxic or mutagenic substances. The invention also includes mutation assays using these cells, and other cells with similar characteristics.

  17. Oxidative stress induced by palytoxin in human keratinocytes is mediated by a H{sup +}-dependent mitochondrial pathway

    SciTech Connect (OSTI)

    Pelin, Marco, E-mail: marco.pelin@phd.units.it [Department of Life Science, University of Trieste, Via L. Giorgieri 7/9, 34127 Trieste (Italy)] [Department of Life Science, University of Trieste, Via L. Giorgieri 7/9, 34127 Trieste (Italy); Ponti, Cristina, E-mail: cponti@units.it [Department of Life Science, University of Trieste, Via L. Giorgieri 7/9, 34127 Trieste (Italy)] [Department of Life Science, University of Trieste, Via L. Giorgieri 7/9, 34127 Trieste (Italy); Sosa, Silvio, E-mail: silvio.sosa@econ.units.it [Department of Life Science, University of Trieste, Via L. Giorgieri 7/9, 34127 Trieste (Italy)] [Department of Life Science, University of Trieste, Via L. Giorgieri 7/9, 34127 Trieste (Italy); Gibellini, Davide, E-mail: davide.gibellini@unibo.it [Department of Haematology and Oncological Sciences, University of Bologna, Via Massarenti 9, 40138 Bologna (Italy)] [Department of Haematology and Oncological Sciences, University of Bologna, Via Massarenti 9, 40138 Bologna (Italy); Florio, Chiara, E-mail: florioc@units.it [Department of Life Science, University of Trieste, Via L. Giorgieri 7/9, 34127 Trieste (Italy)] [Department of Life Science, University of Trieste, Via L. Giorgieri 7/9, 34127 Trieste (Italy); Tubaro, Aurelia, E-mail: tubaro@units.it [Department of Life Science, University of Trieste, Via L. Giorgieri 7/9, 34127 Trieste (Italy)] [Department of Life Science, University of Trieste, Via L. Giorgieri 7/9, 34127 Trieste (Italy)

    2013-01-01T23:59:59.000Z

    In the last decades, massive blooms of palytoxin (PLTX)-producing Ostreopsis cf. ovata have been observed along Mediterranean coasts, usually associated to human respiratory and cutaneous problems. At the molecular level, PLTX induces a massive intracellular Na{sup +} influx due to the transformation of Na{sup +}/K{sup +} ATPase in a cationic channel. Recently, we have demonstrated that Na{sup +} overload is the crucial step in mediating overproduction of reactive oxygen species (ROS) and cell death in human HaCaT keratinocytes, tentatively explaining PLTX-induced skin irritant effects. In the present study the molecular mechanisms of ROS production induced by PLTX-mediated Na{sup +} intracellular overload have been investigated. In HaCaT cells, PLTX exposure caused accumulation of superoxide anion, but not of nitric oxide or peroxynitrite/hydroxyl radicals. Even if RT-PCR and western blot analysis revealed an early NOX-2 and iNOS gene and protein over-expressions, their active involvement seemed to be only partial since selective inhibitors did not completely reduce O{sub 2}{sup ?} production. A significant role of other enzymes (COX-1, COX-2, XO) was not evidenced. Nigericin, that counteracts Na{sup +}-mediated H{sup +}-imbalance, dissipating ?pH across mitochondrial inner membrane, and the uncouplers DNP significantly reduced O{sub 2}{sup ?} production. These inhibitions were synergistic when co-exposed with complex-I inhibitor rotenone. These results suggest a novel mechanism of O{sub 2}{sup ?} production induced by PLTX-mediated ionic imbalance. Indeed, the H{sup +} intracellular overload that follows PLTX-induced intracellular Na{sup +} accumulation, could enhance ?pH across mitochondrial inner membrane, that seems to be the driving force for O{sub 2}{sup ?} production by reversing mitochondrial electron transport. Highlights: ? PLTX induces superoxide (O{sub 2}{sup ?}) production by reversing mitochondrial transport chain. ? The mechanism of O{sub 2}{sup ?} production is dependent on PLTX-induced ionic imbalance. ? The results led to the proposal of a novel mechanism of O{sub 2}{sup ?} production. ? Enhanced Na{sup +}, by increasing H{sup +} level and blocking mitochondrial chain, induces O{sub 2}{sup ?}.

  18. Transcriptional regulatory networks downstream of TAL1/SCL in T-cell acute lymphoblastic leukemia

    E-Print Network [OSTI]

    Liu, Xiaole Shirley

    pathogene- sis of human T-cell acute lymphoblastic leukemia (T-ALL); however, oncogenic transcriptional expression leads to T-cell acute lymphoblastic leukemia (T-ALL). TAL1 is expressed by the leukemic cellsNEOPLASIA Transcriptional regulatory networks downstream of TAL1/SCL in T-cell acute lymphoblastic

  19. Probing the neutron-skin thickness by photon production from reactions induced by intermediate-energy protons

    E-Print Network [OSTI]

    Wei, Gao-Feng

    2015-01-01T23:59:59.000Z

    Photon from neutron-proton bremsstrahlung in p+Pb reactions is examined as a potential probe of the neutron-skin thickness in different centralities and at different proton incident energies. It is shown that the best choice of reaction environment is about 140MeV for the incident proton and the 95\\%-100\\% centrality for the reaction system since the incident proton mainly interacts with neutrons inside the skin of the target and thus leads to different photon production to maximal extent. Moreover, considering two main uncertainties from both photon production probability and nucleon-nucleon cross section in the reaction, I propose to use the ratio of photon production from two reactions to measure the neutron-skin thickness because of its cancellation effects on these uncertainties simultaneously, but the preserved about 13\\%-15\\% sensitivities on the varied neutron-skin thickness from 0.1 to 0.3fm within the current experimental uncertainty range of the neutron-skin size in $^{208}$Pb.

  20. Constraints on neutron skin thickness in 208Pb and density-dependent symmetry energy

    E-Print Network [OSTI]

    Jianmin Dong; Wei Zuo; Jianzhong Gu

    2015-04-09T23:59:59.000Z

    Accurate knowledge about the neutron skin thickness $\\Delta R_{np}$ in $^{208}$Pb has far-reaching implications for different communities of nuclear physics and astrophysics. Yet, the novel Lead Radius Experiment (PREX) did not yield stringent constraint on the $\\Delta R_{np}$ recently. We employ a more practicable strategy currently to probe the neutron skin thickness of $^{208}$Pb based on a high linear correlation between the $\\Delta R_{np}$ and $J-a_{\\text{sym}}$, where $J$ and $a_{\\text{sym}}$ are the symmetry energy (coefficient) of nuclear matter at saturation density and of $^{208}$Pb. An accurate $J-a_{\\text{sym}}$ thus places a strong constraint on the $\\Delta R_{np}$. Compared with the parity-violating asymmetry $A_{\\text{PV}}$ in the PREX, the reliably experimental information on the $J-a_{\\text{sym}}$ is much more easily available attributed to a wealth of measured data on nuclear masses and on decay energies. The density dependence of the symmetry energy is also well constrained with the $J-a_{\\text{sym}}$. Finally, with a `tomoscan' method, we find that one just needs to measure the nucleon densities in $^{208}$Pb starting from $R_{m} = 7.61\\pm0.04$ fm to obtain the $\\Delta R_{np}$ in hadron scattering experiments, regardless of its interior profile that is hampered by the strong absorption.

  1. Constraints on neutron skin thickness in 208Pb and density-dependent symmetry energy

    E-Print Network [OSTI]

    Dong, Jianmin; Gu, Jianzhong

    2015-01-01T23:59:59.000Z

    Accurate knowledge about the neutron skin thickness $\\Delta R_{np}$ in $^{208}$Pb has far-reaching implications for different communities of nuclear physics and astrophysics. Yet, the novel Lead Radius Experiment (PREX) did not yield stringent constraint on the $\\Delta R_{np}$ recently. We employ a more practicable strategy currently to probe the neutron skin thickness of $^{208}$Pb based on a high linear correlation between the $\\Delta R_{np}$ and $J-a_{\\text{sym}}$, where $J$ and $a_{\\text{sym}}$ are the symmetry energy (coefficient) of nuclear matter at saturation density and of $^{208}$Pb. An accurate $J-a_{\\text{sym}}$ thus places a strong constraint on the $\\Delta R_{np}$. Compared with the parity-violating asymmetry $A_{\\text{PV}}$ in the PREX, the reliably experimental information on the $J-a_{\\text{sym}}$ is much more easily available attributed to a wealth of measured data on nuclear masses and on decay energies. The density dependence of the symmetry energy is also well constrained with the $J-a_{\\...

  2. Symmetry energy at subsaturation densities and the neutron skin thickness of 208Pb

    E-Print Network [OSTI]

    Fan, Xiaohua; Zuo, Wei

    2015-01-01T23:59:59.000Z

    The mass-dependent symmetry energy coefficients $a_{sym}(A)$ has been extracted by analysing the heavy nuclear mass differences reducing the uncertainties as far as possible in our previous work. Taking advantage of the obtained symmetry energy coefficient $a_{sym}(A)$ and the density profiles obtained by switching off the Coulomb interaction in $^{208}\\text{Pb}$, we calculated the slope parameter $L_{0.11}$ of the symmetry energy at the density of $0.11\\text{fm}^{-3}$. The calculated $L_{0.11}$ ranges from 40.5 MeV to 60.3 MeV. The slope parameter $L_{0.11}$ of the symmetry energy at the density of $0.11\\text{fm}^{-3}$ is also calculated directly with Skyrme interactions for nuclear matter and is found to have a fine linear relation with the neutron skin thickness of $^{208}\\text{Pb}$, which is the difference of the neutron and proton rms radii of the nucleus. With the linear relation the neutron skin thickness $ \\Delta R_{np} $ of $^{208}\\text{Pb}$ is predicted to be 0.15 - 0.21 fm.

  3. HQ- Human Resources Operations

    Broader source: Energy.gov [DOE]

    HQs Human Recources Operations delivers services, including position management, recruitment, staffing and classification, and reduction in force at Headquarters.  Click the "Contacts" Link to find...

  4. Skin cancer in albinos at the University of Calabar Teaching Hospital, Calabar, Nigeria

    E-Print Network [OSTI]

    Asuquo, M E; Otei, O O; Omotoso, J; Bassey, E E

    2010-01-01T23:59:59.000Z

    of the human P gene in tyrosinase positive oculocutaneousJenkins T, Ramsay M. The tyrosinase positive oculocutaneousrecessive forms involves the tyrosinase gene (OCA1), whereas

  5. Noninvasive Imaging of Administered Progenitor Cells

    SciTech Connect (OSTI)

    Steven R Bergmann, M.D., Ph.D.

    2012-12-03T23:59:59.000Z

    The objective of this research grant was to develop an approach for labeling progenitor cells, specifically those that we had identified as being able to replace ischemic heart cells, so that the distribution could be followed non-invasively. In addition, the research was aimed at determining whether administration of progenitor cells resulted in improved myocardial perfusion and function. The efficiency and toxicity of radiolabeling of progenitor cells was to be evaluated. For the proposed clinical protocol, subjects with end-stage ischemic coronary artery disease were to undergo a screening cardiac positron emission tomography (PET) scan using N-13 ammonia to delineate myocardial perfusion and function. If they qualified based on their PET scan, they would undergo an in-hospital protocol whereby CD34+ cells were stimulated by the administration of granulocytes-colony stimulating factor (G-CSF). CD34+ cells would then be isolated by apharesis, and labeled with indium-111 oxine. Cells were to be re-infused and subjects were to undergo single photon emission computed tomography (SPECT) scanning to evaluate uptake and distribution of labeled progenitor cells. Three months after administration of progenitor cells, a cardiac PET scan was to be repeated to evaluate changes in myocardial perfusion and/or function. Indium oxine is a radiopharmaceutical for labeling of autologous lymphocytes. Indium-111 (In-111) decays by electron capture with a t{sub ½} of 67.2 hours (2.8 days). Indium forms a saturated complex that is neutral, lipid soluble, and permeates the cell membrane. Within the cell, the indium-oxyquinolone complex labels via indium intracellular chelation. Following leukocyte labeling, ~77% of the In-111 is incorporated in the cell pellet. The presence of red cells and /or plasma reduces the labeling efficacy. Therefore, the product needed to be washed to eliminate plasma proteins. This repeated washing can damage cells. The CD34 selected product was a 90-99% pure population of leukocytes. Viability was assessed using Trypan blue histological analysis. We successfully isolated and labeled ~25-30 x 10{sup 7} CD34+ lymphocytes in cytokine mobilized progenitor cell apharesis harvests. Cells were also subjected to a stat gram stain to look for bacterial contamination, stat endotoxin LAL to look for endotoxin contamination, flow cytometry for evaluation of the purity of the cells and 14-day sterility culture. Colony forming assays confirm the capacity of these cells to proliferate and function ex-vivo with CFU-GM values of 26 colonies/ 1 x 10{sup 4} cells plated and 97% viability in cytokine augmented methylcellulose at 10-14 days in CO{sub 2} incubation. We developed a closed-processing system for the product labeling prior to infusion to maintain autologous cell integrity and sterility. Release criteria for the labeled product were documented for viability, cell count and differential, and measured radiolabel. We were successful in labeling the cells with up to 500 uCi/10{sup 8} cells, with viability of >98%. However, due to delays in getting the protocol approved by the FDA, the cells were not infused in humans in this location (although we did successfully use CD34+ cells in humans in a study in Australia). The approach developed should permit labeling of progenitor cells that can be administered to human subjects for tracking. The labeling approach should be useful for all progenitor cell types, although this would need to be verified since different cell lines may have differential radiosensitivity.

  6. Electrochemical cell

    DOE Patents [OSTI]

    Redey, Laszlo I. (Downers Grove, IL); Vissers, Donald R. (Naperville, IL); Prakash, Jai (Downers Grove, IL)

    1994-01-01T23:59:59.000Z

    An electrochemical cell having a bimodal positive electrode, a negative electrode of an alkali metal, and a compatible electrolyte including an alkali metal salt molten at the cell operating temperature. The positive electrode has an electrochemically active layer of at least one transition metal chloride at least partially present as a charging product, and additives of bromide and/or iodide and sulfur in the positive electrode or the electrolyte. Electrode volumetric capacity is in excess of 400 Ah/cm.sup.3 ; the cell can be 90% recharged in three hours and can operate at temperatures below 160.degree. C. There is also disclosed a method of reducing the operating temperature and improving the overall volumetric capacity of an electrochemical cell and for producing a positive electrode having a BET area greater than 6.times.10.sup.4 cm.sup.2 /g of Ni.

  7. Electrochemical cell

    DOE Patents [OSTI]

    Redey, Laszlo I. (6851 Carpenter St., Downers Grove, IL 60516); Vissers, Donald R. (611 Clover Ct., Naperville, IL 60540); Prakash, Jai (2205 Arbor Cir. 8, Downers Grove, IL 60515)

    1996-01-01T23:59:59.000Z

    An electrochemical cell having a bimodal positive electrode, a negative electrode of an alkali metal, and a compatible electrolyte including an alkali metal salt molten at the cell operating temperature. The positive electrode has an electrochemically active layer of at least one transition metal chloride at least partially present as a charging product, and additives of bromide and/or iodide and sulfur in the positive electrode or the electrolyte. Electrode volumetric capacity is in excess of 400 Ah/cm.sup.3 ; the cell can be 90% recharged in three hours and can operate at temperatures below 160.degree. C. There is also disclosed a method of reducing the operating temperature and improving the overall volumetric capacity of an electrochemical cell and for producing a positive electrode having a BET area greater than 6.times.10.sup.4 cm.sup.2 /g of Ni.

  8. Electrochemical cell

    DOE Patents [OSTI]

    Redey, L.I.; Vissers, D.R.; Prakash, J.

    1996-07-16T23:59:59.000Z

    An electrochemical cell is described having a bimodal positive electrode, a negative electrode of an alkali metal, and a compatible electrolyte including an alkali metal salt molten at the cell operating temperature. The positive electrode has an electrochemically active layer of at least one transition metal chloride at least partially present as a charging product, and additives of bromide and/or iodide and sulfur in the positive electrode or the electrolyte. Electrode volumetric capacity is in excess of 400 Ah/cm{sup 3}; the cell can be 90% recharged in three hours and can operate at temperatures below 160 C. There is also disclosed a method of reducing the operating temperature and improving the overall volumetric capacity of an electrochemical cell and for producing a positive electrode having a BET area greater than 6{times}10{sup 4}cm{sup 2}/g of Ni. 6 figs.

  9. Electrochemical cell

    DOE Patents [OSTI]

    Redey, L.I.; Vissers, D.R.; Prakash, J.

    1994-02-01T23:59:59.000Z

    An electrochemical cell is described having a bimodal positive electrode, a negative electrode of an alkali metal, and a compatible electrolyte including an alkali metal salt molten at the cell operating temperature. The positive electrode has an electrochemically active layer of at least one transition metal chloride at least partially present as a charging product, and additives of bromide and/or iodide and sulfur in the positive electrode or the electrolyte. Electrode volumetric capacity is in excess of 400 Ah/cm[sup 3]; the cell can be 90% recharged in three hours and can operate at temperatures below 160 C. There is also disclosed a method of reducing the operating temperature and improving the overall volumetric capacity of an electrochemical cell and for producing a positive electrode having a BET area greater than 6[times]10[sup 4] cm[sup 2]/g of Ni. 8 figures.

  10. Deformability of Plasmodium falciparum parasitized red blood cells

    E-Print Network [OSTI]

    Mills, John Philip, Ph. D. Massachusetts Institute of Technology

    2007-01-01T23:59:59.000Z

    The biophysical properties of the human red blood cell (RBC) permit large deformations required for passage through narrow capillaries and spleen sinusoids. Several pathologic conditions alter RBC deformability that can ...

  11. Microfluidic devices for analysis of red blood cell mechanical properties

    E-Print Network [OSTI]

    Bow, Hansen Chang

    2010-01-01T23:59:59.000Z

    Decreased deformability of human red blood cells (RBCs) is both a cause of disease and biomarker for disease (1). To traverse blood capillaries, the biconcave disk-shaped RBC must deform dramatically, since the diameter ...

  12. Dissecting the transcriptional regulatory network of embryonic stem cells

    E-Print Network [OSTI]

    Cole, Megan F

    2008-01-01T23:59:59.000Z

    The process by which a single fertilized egg develops into a human being with over 200 cell types, each with a distinct gene expression pattern controlling its cellular state, is poorly understood. An understanding of the ...

  13. Targeting nitric oxide signaling with nNOS inhibitors as a novel strategy for the therapy and prevention of human melanoma.

    E-Print Network [OSTI]

    2013-01-01T23:59:59.000Z

    TARGETING N NOS IN HUMAN MELANOMA FIG. 4. Specific nNOSNOS activities in human melanoma Lu1205 cells. Spermidinein the genesis of cutaneous melanoma. Curr Opin Oncol 23: 5.

  14. Highly conductive thermoplastic composites for rapid production of fuel cell bipolar plates

    DOE Patents [OSTI]

    Huang, Jianhua [Blacksburg, VA; Baird, Donald G [Blacksburg, VA; McGrath, James E [Blacksburg, VA

    2008-04-29T23:59:59.000Z

    A low cost method of fabricating bipolar plates for use in fuel cells utilizes a wet lay process for combining graphite particles, thermoplastic fibers, and reinforcing fibers to produce a plurality of formable sheets. The formable sheets are then molded into a bipolar plates with features impressed therein via the molding process. The bipolar plates formed by the process have conductivity in excess of 150 S/cm and have sufficient mechanical strength to be used in fuel cells. The bipolar plates can be formed as a skin/core laminate where a second polymer material is used on the skin surface which provides for enhanced conductivity, chemical resistance, and resistance to gas permeation.

  15. Percutaneous absorption of ( sup 14 C)DDT and ( sup 14 C)benzo(a)pyrene from soil

    SciTech Connect (OSTI)

    Wester, R.C.; Maibach, H.I.; Bucks, D.A.; Sedik, L.; Melendres, J.; Liao, C.; DiZio, S. (Univ. of California School of Medicine, San Francisco (USA))

    1990-10-01T23:59:59.000Z

    The objective was to determine percutaneous absorption of DDT and benzo(a)pyrene in vitro and in vivo from soil into and through skin. Soil (Yolo County 65-California-57-8; 26% sand, 26% clay, 48% silt) was passed through 10-, 20-, and 48-mesh sieves. Soil then retained by 80-mesh was mixed with (14C)-labeled chemical at 10 ppm. Acetone solutions at 10 ppm were prepared for comparative analysis. Human cadaver skin was dermatomed to 500 microns and used in glass diffusion cells with human plasma as the receptor fluid (3 ml/hr flow rate) for a 24-hr skin application time. With acetone vehicle, DDT (18.1 +/- 13.4%) readily penetrated into human skin. Significantly less DDT (1.0 +/- 0.7%) penetrated into human skin from soil. DDT would not partition from human skin into human plasma in the receptor phase (less than 0.1%). With acetone vehicle, benzo(a)pyrene (23.7 +/- 9.7%) readily penetrated into human skin. Significantly less benzo(a)pyrene (1.4 +/- 0.9%) penetrated into human skin from soil. Benzo(a)pyrene would not partition from human skin into human plasma in the receptor phase (less than 0.1%). Substantivity (skin retention) was investigated by applying 14C-labeled chemical to human skin in vitro for only 25 min. After soap and water wash, 16.7 +/- 13.2% of DDT applied in acetone remained absorbed to skin. With soil only 0.25 +/- 0.11% of DDT remained absorbed to skin. After soap and water wash 5.1 +/- 2.1% of benzo(a)pyrene applied in acetone remained absorbed to skin. With soil only 0.14 +/- 0.13% of benzo(a)pyrene remained absorbed to skin.

  16. Cell Stem Cell The Systematic Production

    E-Print Network [OSTI]

    Zandstra, Peter W.

    Cell Stem Cell Review The Systematic Production of Cells for Cell Therapies Daniel C. Kirouac1 to guide the development of next-generation technologies capable of producing cell-based products in a safe will enhance cell therapy product quality and safety, expediting clinical development. Breakthroughs

  17. Micro Fuel Cells Direct Methanol Fuel Cells

    E-Print Network [OSTI]

    Micro Fuel Cells TM Direct Methanol Fuel Cells for Portable Power A Fuel Cell System Developer-17, 2002 Phoenix, Arizona #12;Micro Fuel Cells Direct Methanol Fuel Cells for Portable Power Outline (1 Energy Content (Wh) Volume(cm^3) Li-Ion Battery DMFC #12;Direct Methanol Fuel Cell Technology

  18. Of Microenvironments and Mammary Stem Cells

    SciTech Connect (OSTI)

    LaBarge, Mark A; Petersen, Ole W; Bissell, Mina J

    2007-06-01T23:59:59.000Z

    In most adult tissues there reside pools of stem and progenitor cells inside specialized microenvironments referred to as niches. The niche protects the stem cells from inappropriate expansion and directs their critical functions. Thus guided, stem cells are able to maintain tissue homeostasis throughout the ebb and flow of metabolic and physical demands encountered over a lifetime. Indeed, a pool of stem cells maintains mammary gland structure throughout development, and responds to the physiological demands associated with pregnancy. This review discusses how stem cells were identified in both human and mouse mammary glands; each requiring different techniques that were determined by differing biological needs and ethical constraints. These studies together create a robust portrait of mammary gland biology and identify the location of the stem cell niche, elucidate a developmental hierarchy, and suggest how the niche might be manipulated for therapeutic benefit.

  19. Human Functional Brain Imaging

    E-Print Network [OSTI]

    Rambaut, Andrew

    Human Functional Brain Imaging 1990­2009 September 2011 Portfolio Review Summary Brain Imaging #12 Dale ­ one of our first Trustees. Understanding the brain remains one of our key strategic aims today three-fold: · to identify the key landmarks and influences on the human functional brain imaging

  20. Protection of Human Subjects

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2000-05-15T23:59:59.000Z

    To establish DOE procedures and responsibilities for implementing the policy and requirements set forth in 10 CFR Part 745, Protection of Human Subjects, ad in DOE P 443.1, Policy on the Protection of Human Subjects. Cancels DOE O 1300.3. Canceled by DOE O 443.1A.