National Library of Energy BETA

Sample records for human cortical bone

  1. Irradiation Effects on Human Cortical Bone Fracture Behavior

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

    Irradiation Effects on Human Cortical Bone Fracture Behavior Irradiation Effects on Human Cortical Bone Fracture Behavior Print Wednesday, 28 July 2010 00:00 Human bone is strong ...

  2. Irradiation Effects on Human Cortical Bone Fracture Behavior

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

    Irradiation Effects on Human Cortical Bone Fracture Behavior Print Human bone is strong but still fallible. To better predict fracturing in bone, researchers need a mechanistic...

  3. Irradiation Effects on Human Cortical Bone Fracture Behavior

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

    Irradiation Effects on Human Cortical Bone Fracture Behavior Print Human bone is strong but still fallible. To better predict fracturing in bone, researchers need a mechanistic ...

  4. Irradiation Effects on Human Cortical Bone Fracture Behavior

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

    Irradiation Effects on Human Cortical Bone Fracture Behavior Irradiation Effects on Human Cortical Bone Fracture Behavior Print Wednesday, 28 July 2010 00:00 Human bone is strong but still fallible. To better predict fracturing in bone, researchers need a mechanistic framework to understand the changes taking place on different size scales within bone, as well as the role of sustained irradiation damage. Combining in situ mechanical testing with synchrotron x-ray diffraction imaging and/or

  5. Irradiation Effects on Human Cortical Bone Fracture Behavior

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

    Irradiation Effects on Human Cortical Bone Fracture Behavior Print Human bone is strong but still fallible. To better predict fracturing in bone, researchers need a mechanistic framework to understand the changes taking place on different size scales within bone, as well as the role of sustained irradiation damage. Combining in situ mechanical testing with synchrotron x-ray diffraction imaging and/or tomography, is a popular method of investigating micrometer deformation and fracture behavior in

  6. Irradiation Effects on Human Cortical Bone Fracture Behavior

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

    Irradiation Effects on Human Cortical Bone Fracture Behavior Print Human bone is strong but still fallible. To better predict fracturing in bone, researchers need a mechanistic framework to understand the changes taking place on different size scales within bone, as well as the role of sustained irradiation damage. Combining in situ mechanical testing with synchrotron x-ray diffraction imaging and/or tomography, is a popular method of investigating micrometer deformation and fracture behavior in

  7. Irradiation Effects on Human Cortical Bone Fracture Behavior

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

    Irradiation Effects on Human Cortical Bone Fracture Behavior Print Human bone is strong but still fallible. To better predict fracturing in bone, researchers need a mechanistic framework to understand the changes taking place on different size scales within bone, as well as the role of sustained irradiation damage. Combining in situ mechanical testing with synchrotron x-ray diffraction imaging and/or tomography, is a popular method of investigating micrometer deformation and fracture behavior in

  8. Irradiation Effects on Human Cortical Bone Fracture Behavior

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

    Irradiation Effects on Human Cortical Bone Fracture Behavior Print Human bone is strong but still fallible. To better predict fracturing in bone, researchers need a mechanistic framework to understand the changes taking place on different size scales within bone, as well as the role of sustained irradiation damage. Combining in situ mechanical testing with synchrotron x-ray diffraction imaging and/or tomography, is a popular method of investigating micrometer deformation and fracture behavior in

  9. Irradiation Effects on Human Cortical Bone Fracture Behavior

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

    Irradiation Effects on Human Cortical Bone Fracture Behavior Print Human bone is strong but still fallible. To better predict fracturing in bone, researchers need a mechanistic framework to understand the changes taking place on different size scales within bone, as well as the role of sustained irradiation damage. Combining in situ mechanical testing with synchrotron x-ray diffraction imaging and/or tomography, is a popular method of investigating micrometer deformation and fracture behavior in

  10. Irradiation Effects on Human Cortical Bone Fracture Behavior

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

    Irradiation Effects on Human Cortical Bone Fracture Behavior Print Human bone is strong but still fallible. To better predict fracturing in bone, researchers need a mechanistic framework to understand the changes taking place on different size scales within bone, as well as the role of sustained irradiation damage. Combining in situ mechanical testing with synchrotron x-ray diffraction imaging and/or tomography, is a popular method of investigating micrometer deformation and fracture behavior in

  11. Irradiation Effects on Human Cortical Bone Fracture Behavior

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

    bone is made up of fibrous polymer collagen and hard mineral nanoparticals of hydroxyapatite that reinforce it. At the micron level, bone contains osteons - bone cylinders...

  12. The significance of crack-resistance curves to the mixed-mode fracture toughness of human cortical bone

    SciTech Connect (OSTI)

    Zimmermann, Elizabeth A.; Launey, Maximilien E.; Ritchie, Robert O.

    2010-03-25

    The majority of fracture mechanics studies on the toughness of bone have been performed under tensile loading. However, it has recently been shown that the toughness of human cortical bone in the transverse (breaking) orientation is actually much lower in shear (mode II) than in tension (mode I); a fact that is physiologically relevant as in vivo bone is invariably loaded multiaxially. Since bone is a material that derives its fracture resistance primarily during crack growth through extrinsic toughening mechanisms, such as crack deflection and bridging, evaluation of its toughness is best achieved through measurements of the crack-resistance or R-curve, which describes the fracture toughness as a function of crack extension. Accordingly, in this study, we attempt to measure for the first time the R-curve fracture toughness of human cortical bone under physiologically relevant mixed-mode loading conditions. We show that the resulting mixed-mode (mode I + II) toughness depends strongly on the crack trajectory and is the result of the competition between the paths of maximum mechanical driving force and 'weakest' microstructural resistance.

  13. On the effect of x-ray irradiation on the deformation and fracture behavior of human cortical bone

    SciTech Connect (OSTI)

    Barth, Holly D.; Launey, Maximilien E.; McDowell, Alastair A.; Ager III, Joel W.; Ritchie, Robert O.

    2010-01-10

    In situ mechanical testing coupled with imaging using high-energy synchrotron x-ray diffraction or tomography imaging is gaining in popularity as a technique to investigate micrometer and even sub-micrometer deformation and fracture mechanisms in mineralized tissues, such as bone and teeth. However, the role of the irradiation in affecting the nature and properties of the tissue is not always taken into account. Accordingly, we examine here the effect of x-ray synchrotron-source irradiation on the mechanistic aspects of deformation and fracture in human cortical bone. Specifically, the strength, ductility and fracture resistance (both work-of-fracture and resistance-curve fracture toughness) of human femoral bone in the transverse (breaking) orientation were evaluated following exposures to 0.05, 70, 210 and 630 kGy irradiation. Our results show that the radiation typically used in tomography imaging can have a major and deleterious impact on the strength, post-yield behavior and fracture toughness of cortical bone, with the severity of the effect progressively increasing with higher doses of radiation. Plasticity was essentially suppressed after as little as 70 kGy of radiation; the fracture toughness was decreased by a factor of five after 210 kGy of radiation. Mechanistically, the irradiation was found to alter the salient toughening mechanisms, manifest by the progressive elimination of the bone's capacity for plastic deformation which restricts the intrinsic toughening from the formation 'plastic zones' around crack-like defects. Deep-ultraviolet Raman spectroscopy indicated that this behavior could be related to degradation in the collagen integrity.

  14. Characterization of the effects of x-ray irradiation on the hierarchical structure and mechanical properties of human cortical bone

    SciTech Connect (OSTI)

    Barth, Holly; Zimmermann, Elizabeth; Schaible, Eric; Tang, Simon; Alliston, Tamara; Ritchie, Robert

    2011-08-19

    Bone comprises a complex structure of primarily collagen, hydroxyapatite and water, where each hierarchical structural level contributes to its strength, ductility and toughness. These properties, however, are degraded by irradiation, arising from medical therapy or bone-allograft sterilization. We provide here a mechanistic framework for how irradiation affects the nature and properties of human cortical bone over a range of characteristic (nano to macro) length-scales, following x-ray exposures up to 630 kGy. Macroscopically, bone strength, ductility and fracture resistance are seen to be progressively degraded with increasing irradiation levels. At the micron-scale, fracture properties, evaluated using in-situ scanning electron microscopy and synchrotron x-ray computed micro-tomography, provide mechanistic information on how cracks interact with the bone-matrix structure. At sub-micron scales, strength properties are evaluated with in-situ tensile tests in the synchrotron using small-/wide-angle x-ray scattering/diffraction, where strains are simultaneously measured in the macroscopic tissue, collagen fibrils and mineral. Compared to healthy bone, results show that the fibrillar strain is decreased by ~40% following 70 kGy exposures, consistent with significant stiffening and degradation of the collagen. We attribute the irradiation-induced deterioration in mechanical properties to mechanisms at multiple length-scales, including changes in crack paths at micron-scales, loss of plasticity from suppressed fibrillar sliding at sub-micron scales, and the loss and damage of collagen at the nano-scales, the latter being assessed using Raman and Fourier-Transform-Infrared spectroscopy and a fluorometric assay.

  15. Age-related changes in the plasticity and toughness of human cortical bone at multiple length-scales

    SciTech Connect (OSTI)

    Zimmermann, Elizabeth A.; Schaible, Eric; Bale, Hrishikesh; Barth, Holly D.; Tang, Simon Y.; Reichert, Peter; Busse, Bjoern; Alliston, Tamara; Ager III, Joel W.; Ritchie, Robert O.

    2011-08-10

    The structure of human cortical bone evolves over multiple length-scales from its basic constituents of collagen and hydroxyapatite at the nanoscale to osteonal structures at nearmillimeter dimensions, which all provide the basis for its mechanical properties. To resist fracture, bone’s toughness is derived intrinsically through plasticity (e.g., fibrillar sliding) at structural-scales typically below a micron and extrinsically (i.e., during crack growth) through mechanisms (e.g., crack deflection/bridging) generated at larger structural-scales. Biological factors such as aging lead to a markedly increased fracture risk, which is often associated with an age-related loss in bone mass (bone quantity). However, we find that age-related structural changes can significantly degrade the fracture resistance (bone quality) over multiple lengthscales. Using in situ small-/wide-angle x-ray scattering/diffraction to characterize sub-micron structural changes and synchrotron x-ray computed tomography and in situ fracture-toughness measurements in the scanning electron microscope to characterize effects at micron-scales, we show how these age-related structural changes at differing size-scales degrade both the intrinsic and extrinsic toughness of bone. Specifically, we attribute the loss in toughness to increased non-enzymatic collagen cross-linking which suppresses plasticity at nanoscale dimensions and to an increased osteonal density which limits the potency of crack-bridging mechanisms at micron-scales. The link between these processes is that the increased stiffness of the cross-linked collagen requires energy to be absorbed by “plastic” deformation at higher structural levels, which occurs by the process of microcracking.

  16. Recombinant human bone morphogenetic protein induces bone formation

    SciTech Connect (OSTI)

    Wang, E.A.; Rosen, V.; D'Alessandro, J.S.; Bauduy, M.; Cordes, P.; Harada, T.; Israel, D.I.; Hewick, R.M.; Kerns, K.M.; LaPan, P.; Luxenberg, D.P.; McQuaid, D.; Moutsatsos, I.K.; Nove, J.; Wozney, J.M. )

    1990-03-01

    The authors have purified and characterized active recombinant human bone morphogenetic protein (BMP) 2A. Implantation of the recombinant protein in rats showed that a single BMP can induce bone formation in vivo. A dose-response and time-course study using the rat ectopic bone formation assay revealed that implantation of 0.5-115 {mu}g of partially purified recombinant human BMP-2A resulted in cartilage by day 7 and bone formation by day 14. The time at which bone formation occurred was dependent on the amount of BMP-2A implanted; at high doses bone formation could be observed at 5 days. The cartilage- and bone-inductive activity of the recombinant BMP-2A is histologically indistinguishable from that of bone extracts. Thus, recombinant BMP-2A has therapeutic potential to promote de novo bone formation in humans.

  17. Irradiation Effects on Human Cortical Bone Fracture Behavior

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

    ... Specifically, at the nanoscale, irradiation leads to a marked increase in collagen cross-linking and molecular damage (assessed using Raman spectroscopy), resulting in a loss in ...

  18. Irradiation Effects on Human Cortical Bone Fracture Behavior

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

    to a marked increase in collagen cross-linking and molecular damage (assessed using Raman spectroscopy), resulting in a loss in strength and plasticity. Additionally, at...

  19. On the multiscale origins of fracture resistance in human bone and its biological degradation

    SciTech Connect (OSTI)

    Zimmermann, Elizabeth A.; Barth, Holly D.; Ritchie, Robert O.

    2012-03-09

    Akin to other mineralized tissues, human cortical bone can resist deformation and fracture due to the nature of its hierarchical structure, which spans the molecular to macroscopic length-scales. Deformation at the smallest scales, mainly through the composite action of the mineral and collagen, contributes to bone?s strength or intrinsic fracture resistance, while crack-tip shielding mechanisms active on the microstructural scale contribute to the extrinsic fracture resistance once cracking begins. The efficiency with which these structural features can resist fracture at both small and large length-scales becomes severely degraded with such factors as aging, irradiation and disease. Indeed aging and irradiation can cause changes to the cross-link profile at fibrillar length-scales as well as changes at the three orders of magnitude larger scale of the osteonal structures, both of which combine to inhibit the bone's overall resistance to the initiation and growth of cracks.

  20. The Ductility of Human Jaw Bone Attached to a Tooth | Stanford...

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

    The Ductility of Human Jaw Bone Attached to a Tooth Saturday, May 31, 2014 In a bone-tooth ... of the tooth root and alveolar bone (human jaw bone) of the socket is permitted by an ...

  1. Intrinsic mechanical behavior of femoral cortical bone in young, osteoporotic and bisphosphonate-treated individuals in low- and high energy fracture conditions

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Zimmermann, Elizabeth A.; Schaible, Eric; Gludovatz, Bernd; Schmidt, Felix N.; Riedel, Christoph; Krause, Matthias; Vettorazzi, Eik; Acevedo, Claire; Hahn, Michael; Püschel, Klaus; et al

    2016-02-16

    Bisphosphonates are a common treatment to reduce osteoporotic fractures. This treatment induces osseous structural and compositional changes accompanied by positive effects on osteoblasts and osteocytes. Here, we test the hypothesis that restored osseous cell behavior, which resembles characteristics of younger, healthy cortical bone, leads to improved bone quality. Microarchitecture and mechanical properties of young, treatment-naïve osteoporosis, and bisphosphonate-treated cases were investigated in femoral cortices. Tissue strength was measured using three-point bending. Collagen fibril-level deformation was assessed in non-traumatic and traumatic fracture states using synchrotron small-angle x-ray scattering (SAXS) at low and high strain rates. The lower modulus, strength and fibrilmore » deformation measured at low strain rates reflects susceptibility for osteoporotic low-energy fragility fractures. Independent of age, disease and treatment status, SAXS revealed reduced fibril plasticity at high strain rates, characteristic of traumatic fracture. We find the significantly reduced mechanical integrity in osteoporosis may originate from porosity and alterations to the intra/extrafibrillar structure, while the fibril deformation under treatment indicates improved nano-scale characteristics. In conclusion, losses in strength and fibril deformation at low strain rates correlate with the occurrence of fragility fractures in osteoporosis, while improvements in structural and mechanical properties following bisphosphonate treatment may foster resistance to fracture during physiological strain rates.« less

  2. Bone sarcoma in humans induced by radium: A threshold response?

    SciTech Connect (OSTI)

    Rowland, R.E.

    1996-08-01

    The radium 226 and radium 228 have induced malignancies in the skeleton (primarily bone sarcomas) of humans. They have also induced carcinomas in the paranasal sinuses and mastoid air cells. There is no evidence that any leukemias or any other solid cancers have been induced by internally deposited radium. This paper discuses a study conducted on the dial painter population. This study made a concerted effort to verify, for each of the measured radium cases, the published values of the skeletal dose and the initial intake of radium. These were derived from body content measurements made some 40 years after the radium intake. Corrections to the assumed radium retention function resulted in a considerable number of dose changes. These changes have changed the shape of the dose response function. It now appears that the induction of bone sarcomas is a threshold process.

  3. The Ductility of Human Jaw Bone Attached to a Tooth | Stanford Synchrotron

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

    Radiation Lightsource The Ductility of Human Jaw Bone Attached to a Tooth Saturday, May 31, 2014 In a bone-tooth fibrous joint, the articulation between harder materials such as the cementum of the tooth root and alveolar bone (human jaw bone) of the socket is permitted by an intervening softer periodontal ligament. To investigate adaptations of the bony socket, basic principles from tribology, mechanics of materials, and materials science were used to postulate that the ductile nature of an

  4. Mechanistic aspects of fracture and R-curve behavior in elk antler bone

    SciTech Connect (OSTI)

    Launey, Maximilien E.; Chen, Po-Yu; McKittrick, Joanna; Ritchie, Robert O.

    2009-11-23

    Bone is an adaptative material that is designed for different functional requirements; indeed, bones have a variety of properties depending on their role in the body. To understand the mechanical response of bone requires the elucidation of its structure-function relationships. Here, we examine the fracture toughness of compact bone of elk antler which is an extremely fast growing primary bone designed for a totally different function than human (secondary) bone. We find that antler in the transverse (breaking) orientation is one of the toughest biological materials known. Its resistance to fracture is achieved during crack growth (extrinsically) by a combination of gross crack deflection/twisting and crack bridging via uncracked 'ligaments' in the crack wake, both mechanisms activated by microcracking primarily at lamellar boundaries. We present an assessment of the toughening mechanisms acting in antler as compared to human cortical bone, and identify an enhanced role of inelastic deformation in antler which further contributes to its (intrinsic) toughness.

  5. Bioactive Glass Scaffolds for Bone Regeneration

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

    with cortical and trabecular bone and literature values of porous glass and hydroxyapatite scaffolds. Each style of point corresponds to a different literature value....

  6. Method for fusing bone

    DOE Patents [OSTI]

    Mourant, Judith R.; Anderson, Gerhard D.; Bigio, Irving J.; Johnson, Tamara M.

    1996-01-01

    Method for fusing bone. The present invention is a method for joining hard tissue which includes chemically removing the mineral matrix from a thin layer of the surfaces to be joined, placing the two bones together, and heating the joint using electromagnetic radiation. The goal of the method is not to produce a full-strength weld of, for example, a cortical bone of the tibia, but rather to produce a weld of sufficient strength to hold the bone halves in registration while either external fixative devices are applied to stabilize the bone segments, or normal healing processes restore full strength to the tibia.

  7. Method for fusing bone

    DOE Patents [OSTI]

    Mourant, J.R.; Anderson, G.D.; Bigio, I.J.; Johnson, T.M.

    1996-03-12

    The present invention is a method for joining hard tissue which includes chemically removing the mineral matrix from a thin layer of the surfaces to be joined, placing the two bones together, and heating the joint using electromagnetic radiation. The goal of the method is not to produce a full-strength weld of, for example, a cortical bone of the tibia, but rather to produce a weld of sufficient strength to hold the bone halves in registration while either external fixative devices are applied to stabilize the bone segments, or normal healing processes restore full strength to the tibia.

  8. Identification and characterization of cellular binding proteins (receptors) for recombinant human bone morphogenetic protein 2B, an initiator of bone differentiation cascade

    SciTech Connect (OSTI)

    Paralkar, V.M.; Reddi, A.H. ); Hammonds, R.G. )

    1991-04-15

    Bone morphogenetic protein 2B (BMP 2B), is a heparin-binding bone differentiation factor that initiates endochondral bone formation in rats when implanted subcutaneously. The molecular mechanism of action of this differentiation factor is not known, and as a first step the authors have examined BMP 2B-responsive cells for the presence of specific cellular binding proteins. Using {sup 125}I-labeled BMP 2B, specific high-affinity binding sites for recombinant human BMP 2B on MC3T3 E1 osteoblast-like cells as well as on NIH 3T3 fibroblasts were identified. Platelet-derived growth factor, epidermal growth factor, and transforming growth factor {beta} did not compete for the binding of radiolabeled BMP 2B. The binding of BMP 2B is a time- and temperature-dependent process. Chemical crosslinking of radiolabeled BMP showed two components. These data demonstrate specific, high-affinity cell-surface binding proteins for BMP 2B.

  9. Modeling cortical circuits.

    SciTech Connect (OSTI)

    Rohrer, Brandon Robinson; Rothganger, Fredrick H.; Verzi, Stephen J.; Xavier, Patrick Gordon

    2010-09-01

    The neocortex is perhaps the highest region of the human brain, where audio and visual perception takes place along with many important cognitive functions. An important research goal is to describe the mechanisms implemented by the neocortex. There is an apparent regularity in the structure of the neocortex [Brodmann 1909, Mountcastle 1957] which may help simplify this task. The work reported here addresses the problem of how to describe the putative repeated units ('cortical circuits') in a manner that is easily understood and manipulated, with the long-term goal of developing a mathematical and algorithmic description of their function. The approach is to reduce each algorithm to an enhanced perceptron-like structure and describe its computation using difference equations. We organize this algorithmic processing into larger structures based on physiological observations, and implement key modeling concepts in software which runs on parallel computing hardware.

  10. The systemic delivery of an oncolytic adenovirus expressing decorin inhibits bone metastasis in a mouse model of human prostate cancer

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Xu, Weidong; Neill, Thomas; Yang, Yuefeng; Hu, Zebin; Cleveland, Elyse; Wu, Ying; Hutten, Ryan; Xiao, Xianghui; Stock, Stuart R.; Shevrin, Daniel; et al

    2014-12-11

    In an effort to develop a new therapy for prostate cancer bone metastases, we have created Ad.dcn, a recombinant oncolytic adenovirus carrying the human decorin gene. Infection of PC-3 and DU-145, the human prostate tumor cells, with Ad.dcn or a non-replicating adenovirus Ad(E1-).dcn resulted in decorin expression; Ad.dcn produced high viral titers and cytotoxicity in human prostate tumor cells. Adenoviral-mediated decorin expression inhibited Met, the Wnt/β- catenin signaling axis, vascular endothelial growth factor A, reduced mitochondrial DNA levels, and inhibited tumor cell migration. To examine the anti-tumor response of Ad.dcn, PC-3-luc cells were inoculated in the left heart ventricle tomore » establish bone metastases in nude mice. Ad.dcn, in conjunction with control replicating and non-replicating vectors were injected via tail vein. The real-time monitoring of mice, once a week, by bioluminescence imaging and X-ray radiography showed that Ad.dcn produced significant inhibition of skeletal metastases. Analyses of the mice at the terminal time point indicated a significant reduction in the tumor burden, osteoclast number, serum TRACP 5b levels, osteocalcin levels, hypercalcemia, inhibition of cancer cachexia, and an increase in the animal survival. Finally, based on these studies, we believe that Ad.dcn can be developed as a potential new therapy for prostate cancer bone metastasis.« less

  11. Method for palliation of pain in human bone cancer using therapeutic tin-117m compositions

    DOE Patents [OSTI]

    Srivastava, S.C.; Meinken, G.E.; Mausner, L.F.; Atkins, H.L.

    1998-12-29

    The invention provides a method for the palliation of bone pain due to cancer by the administration of a unique dosage of a tin-117m (Sn-117m) stannic chelate complex in a pharmaceutically acceptable composition. In addition, the invention provides a method for simultaneous palliation of bone pain and radiotherapy in cancer patients using compositions containing Sn-117m chelates. The invention also provides a method for palliating bone pain in cancer patients using Sn-117m-containing compositions and monitoring patient status by imaging the distribution of the Sn-117m in the patients. Also provided are pharmaceutically acceptable compositions containing Sn-117m chelate complexes for the palliation of bone pain in cancer patients. 5 figs.

  12. Method for palliation of pain in human bone cancer using therapeutic tin-117m compositions

    DOE Patents [OSTI]

    Srivastava, Suresh C.; Meinken, George E.; Mausner, Leonard F.; Atkins, Harold L.

    1998-12-29

    The invention provides a method for the palliation of bone pain due to cancer by the administration of a unique dosage of a tin-117m (Sn-117m) stannic chelate complex in a pharmaceutically acceptable composition. In addition, the invention provides a method for simultaneous palliation of bone pain and radiotherapy in cancer patients using compositions containing Sn-117m chelates. The invention also provides a method for palliating bone pain in cancer patients using Sn-117m-containing compositions and monitoring patient status by imaging the distribution of the Sn-117m in the patients. Also provided are pharmaceutically acceptable compositions containing Sn-117m chelate complexes for the palliation of bone pain in cancer patients.

  13. Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine

    SciTech Connect (OSTI)

    Tomar, Geetanjali B.; Srivastava, Rupesh K.; Gupta, Navita; Barhanpurkar, Amruta P.; Pote, Satish T.; Jhaveri, Hiral M.; Mishra, Gyan C.; Wani, Mohan R.

    2010-03-12

    Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation into multiple cell lineages. Presently, bone marrow is considered as a prime source of MSCs; however, there are some drawbacks and limitations in use of these MSCs for cell therapy. In this study, we demonstrate that human gingival tissue-derived MSCs have several advantages over bone marrow-derived MSCs. Gingival MSCs are easy to isolate, homogenous and proliferate faster than bone marrow MSCs without any growth factor. Importantly, gingival MSCs display stable morphology and do not loose MSC characteristic at higher passages. In addition, gingival MSCs maintain normal karyotype and telomerase activity in long-term cultures, and are not tumorigenic. Thus, we reveal that human gingiva is a better source of MSCs than bone marrow, and large number of functionally competent clinical grade MSCs can be generated in short duration for cell therapy in regenerative medicine and tissue engineering.

  14. Fine mapping of the human bone morphogenetic protein-4 gene (BMP4) to chromosome 14q22-q23 by in situ hybridization

    SciTech Connect (OSTI)

    Wijngaard, A. van den; Boersma, C.J.C.; Olijve, W.

    1995-06-10

    Bone morphogenetic protein-4 (BMP-4) is a member of the transforming growth factor-{beta} (TGF-{beta}) superfamily and is involved in morphogenesis and bone cell differentiation. Recombinant BMP-4 can induce ectopic cartilage and bone formation when implanted subcutaneously or intramuscularly in rodents. This ectopic bone formation process resembles the process of bone formation during embryogenesis and fracture healing. A cosmid clone containing the complete human bone morphogenetic protein-4 gene (BMP4) was isolated (details to be published elsewhere) and used as a probe to determine the precise chromosomal localization of the human BMP4 gene. This cosmid clone was labeled with biotin-14-dATP and hybridized in situ to chromosomal preparations of metaphase cells as described previously. In 20 metaphase preparations, an intense and specific fluorescence signal (FITC) was detected on the q arm of chromosome 14. The DAPI-counterstained chromosomes were computer-converted into GTG-like banding patterns, allowing the regional localization of BMP4 within 14q22-q23. 10 refs., 1 fig.

  15. Comparative study of the chondrogenic potential of human bone marrow stromal cells, neonatal chondrocytes and adult chondrocytes

    SciTech Connect (OSTI)

    Saha, Sushmita; Kirkham, Jennifer; NIHR Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Chapel Allerton Hospital, Leeds LS74SA ; Wood, David; Curran, Stephen; Yang, Xuebin; NIHR Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Chapel Allerton Hospital, Leeds LS74SA

    2010-10-22

    Research highlights: {yields} This study has characterised three different cell types under conditions similar to those used for autologous chondrocyte implantation (ACI) for applications in cartilage repair/regeneration. {yields} Compared for the first time the chondrogenic potential of neonatal chondrocytes with human bone marrow stromal cells (HBMSCs) and adult chondrocytes. {yields} Demonstrated that adult chondrocytes hold greatest potential for use in ACI based on their higher proliferation rates, lower alkaline phosphatise activity and enhanced expression of chondrogenic genes. {yields} Demonstrated the need for chondroinduction as a necessary pre-requisite to efficient chondrogenesis in vitro and, by extrapolation, for cell based therapy (e.g. ACI or cartilage tissue engineering). -- Abstract: Cartilage tissue engineering is still a major clinical challenge with optimisation of a suitable source of cells for cartilage repair/regeneration not yet fully addressed. The aims of this study were to compare and contrast the differences in chondrogenic behaviour between human bone marrow stromal cells (HBMSCs), human neonatal and adult chondrocytes to further our understanding of chondroinduction relative to cell maturity and to identify factors that promote chondrogenesis and maintain functional homoeostasis. Cells were cultured in monolayer in either chondrogenic or basal medium, recapitulating procedures used in existing clinical procedures for cell-based therapies. Cell doubling time, morphology and alkaline phosphatase specific activity (ALPSA) were determined at different time points. Expression of chondrogenic markers (SOX9, ACAN and COL2A1) was compared via real time polymerase chain reaction. Amongst the three cell types studied, HBMSCs had the highest ALPSA in basal culture and lowest ALPSA in chondrogenic media. Neonatal chondrocytes were the most proliferative and adult chondrocytes had the lowest ALPSA in basal media. Gene expression analysis revealed

  16. Biodegradable synthetic bone composites

    DOE Patents [OSTI]

    Liu, Gao; Zhao, Dacheng; Saiz, Eduardo; Tomsia, Antoni P.

    2013-01-01

    The invention provides for a biodegradable synthetic bone composition comprising a biodegradable hydrogel polymer scaffold comprising a plurality of hydrolytically unstable linkages, and an inorganic component; such as a biodegradable poly(hydroxyethylmethacrylate)/hydroxyapatite (pHEMA/HA) hydrogel composite possessing mineral content approximately that of human bone.

  17. New insights to the role of aryl hydrocarbon receptor in bone phenotype and in dioxin-induced modulation of bone microarchitecture and material properties

    SciTech Connect (OSTI)

    Herlin, Maria; Finnil, Mikko A.J.; Zioupos, Peter; Aula, Antti; Risteli, Juha; Miettinen, Hanna M.; Jms, Timo; Tuukkanen, Juha; Korkalainen, Merja; Hkansson, Helen; Viluksela, Matti

    2013-11-15

    Bone is a target for high affinity aryl hydrocarbon receptor (AHR) ligands, such as dioxins. Although bone morphology, mineral density and strength are sensitive endpoints of dioxin toxicity, less is known about effects on bone microarchitecture and material properties. This study characterizes TCDD-induced modulations of bone tissue, and the role of AHR in dioxin-induced bone toxicity and for normal bone phenotype. Six AHR-knockout (Ahr{sup ?/?}) and wild-type (Ahr{sup +/+}) mice of both genders were exposed to TCDD weekly for 10 weeks, at a total dose of 200 ?g/kg bw. Bones were examined with micro-computed tomography, nanoindentation and biomechanical testing. Serum levels of bone remodeling markers were analyzed, and the expression of genes related to osteogenic differentiation was profiled using PCR array. In Ahr{sup +/+} mice, TCDD-exposure resulted in harder bone matrix, thinner and more porous cortical bone, and a more compact trabecular bone compartment. Bone remodeling markers and altered expression of a number of osteogenesis related genes indicated imbalanced bone remodeling. Untreated Ahr{sup ?/?} mice displayed a slightly modified bone phenotype as compared with untreated Ahr{sup +/+} mice, while TCDD exposure caused only a few changes in bones of Ahr{sup ?/?} mice. Part of the effects of both TCDD-exposure and AHR-deficiency were gender dependent. In conclusion, exposure of adult mice to TCDD resulted in harder bone matrix, thinner cortical bone, mechanically weaker bones and most notably, increased trabecular bone volume fraction in Ahr{sup +/+} mice. AHR is involved in bone development of a normal bone phenotype, and is crucial for manifestation of TCDD-induced bone alterations. - Highlights: TCDD disrupts bone remodeling resulting in altered cortical and trabecular bone. In trabecular bone an anabolic effect is observed. Cortical bone is thinner, more porous, harder, stiffer and mechanically weaker. AHR ablation results in increased

  18. Effects of microstructure and water on the electrical potentials in bone induced by ultrasound irradiation

    SciTech Connect (OSTI)

    Tsuneda, H.; Matsukawa, S.; Takayanagi, S.; Matsukawa, M.; Mizuno, K.; Yanagitani, T.

    2015-02-16

    The healing mechanism of bone fractures by low intensity pulse ultrasound is yet to be fully understood. There have been many discussions regarding how the high frequency dynamic stress can stimulate numerous cell types through various pathways. As one possible initial process of this mechanism, we focus on the piezoelectricity of bone and demonstrate that bone can generate electrical potentials by ultrasound irradiation in the MHz range. We have fabricated ultrasonic bone transducers using bovine cortical bone as the piezoelectric device. The ultrasonically induced electrical potentials in the transducers change as a function of time during immersed ultrasonic pulse measurements and become stable when the bone is fully wet. In addition, the magnitude of the induced electrical potentials changes owing to the microstructure in the cortical bone. The potentials of transducers with haversian structure bone are higher than those of plexiform structure bone, which informs about the effects of bone microstructure on the piezoelectricity.

  19. Bone growth and turnover in progesterone receptor knockout mice.

    SciTech Connect (OSTI)

    Rickard, David J.; Iwaniec, Urszula T.; Evans, Glenda; Hefferan, Theresa E.; Hunter, Jaime C.; Waters, Katrina M.; Lydon, John P.; O'Malley, Bert W.; Khosla, Sundeep; Spelsberg, Thomas C.; Turner, Russell T.

    2008-05-01

    The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through the PR is necessary for normal bone growth and turnover, we performed histomorphometric and mCT analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 weeks of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain and tibia longitudinal bone growth was normal in PRKO mice. In contrast, total and cortical bone mass were increased in long bones of post-pubertal (12 and 26-week-old) PRKO mice, whereas cancellous bone mass was normal in the tibia but increased in the humerus. The striking 57% decrease in cancellous bone from the proximal tibia metaphysis which occurred between 6 and 26 weeks in WT mice was abolished in PRKO mice. The improved bone balance in aging PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice attenuates the accumulation of cortical bone mass during adolescence and is required for early age-related loss of cancellous bone.

  20. 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; Soubrier, Anne-Sophie; Thouverey, Cyril; Cortet, Bernard; Broux, Odile; Caverzasio, Joseph; Hardouin, Pierre

    2012-11-02

    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.

  1. Transgenic mice that express the human multidrug-resistance gene in bone marrow enable a rapid identification of agents that reverse drug resistance

    SciTech Connect (OSTI)

    Mickisch, G.H.; Merlino, G.T.; Galski, H.; Gottesman, M.M.; Pastan, I. )

    1991-01-15

    The development of preclinical models for the rapid testing of agents that circumvent multidrug resistance in cancer is a high priority of research on drug resistance. A common form of multidrug resistance in human cancer results from expression of the MDR1 gene, which encodes a M{sub r} 170,000 glycoprotein that functions as a plasma membrane energy-dependent multidrug efflux pump. The authors have engineered transgenic mice that express this multidrug transporter in their bone marrow and demonstrated that these animals are resistant to leukopenia by a panel of anticancer drugs including anthracyclines, vinca alkaloids, etoposide, taxol, and actinomycin D. Differential leukocyte counts indicate that both neutrophils and lympohcytes are pretected. Drugs such as cisplatin, methotrexate, and 5-fluorouracil, which are not handled by the multidrug transporter, produce bone marrow suppression in both normal and transgenic mice. The resistance conferred by the MDR1 gene can be circumvented in a dose-dependent manner by simultaneous administration of agents previously shown to be inhibitors of the multidrug transporter in vitro, including verapamil isomers, quinidine, and quinine. They conclude that MDR1-transgenic mice provide a rapid and reliable system to determine the bioactivity of agents that reverse multidrug resistance in animals.

  2. Potential role of 20S proteasome in maintaining stem cell integrity of human bone marrow stromal cells in prolonged culture expansion

    SciTech Connect (OSTI)

    Lu, Li; Song, Hui-Fang; Zhang, Wei-Guo; Liu, Xue-Qin; Zhu, Qian; Cheng, Xiao-Long; Yang, Gui-Jiao; Li, Ang; Xiao, Zhi-Cheng; Monash Immunology and Stem Cell Laboratories, Monash University, Clayton, Melbourne 3800

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer Prolonged culture expansion retards proliferation and induces senescence of hBMSCs. Black-Right-Pointing-Pointer Reduced 20S proteasomal activity and expression potentially contribute to cell aging. Black-Right-Pointing-Pointer MG132-mediated 20S proteasomal inhibition induces senescence-like phenotype. Black-Right-Pointing-Pointer 18{alpha}-GA stimulates proteasomal activity and restores replicative senescence. Black-Right-Pointing-Pointer 18{alpha}-GA retains differentiation without affecting stem cell characterizations. -- Abstract: Human bone marrow stromal cells (hBMSCs) could be used in clinics as precursors of multiple cell lineages following proper induction. Such application is impeded by their characteristically short lifespan, together with the increasing loss of proliferation capability and progressive reduction of differentiation potential after the prolonged culture expansion. In the current study, we addressed the possible role of 20S proteasomes in this process. Consistent with prior reports, long-term in vitro expansion of hBMSCs decreased cell proliferation and increased replicative senescence, accompanied by reduced activity and expression of the catalytic subunits PSMB5 and PSMB1, and the 20S proteasome overall. Application of the proteasome inhibitor MG132 produced a senescence-like phenotype in early passages, whereas treating late-passage cells with 18{alpha}-glycyrrhetinic acid (18{alpha}-GA), an agonist of 20S proteasomes, delayed the senescence progress, enhancing the proliferation and recovering the capability of differentiation. The data demonstrate that activation of 20S proteasomes assists in counteracting replicative senescence of hBMSCs expanded in vitro.

  3. 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; Nemoto, Eiji; Kanaya, Sousuke; Hamaji, Nozomu; Sato, Hisae; Shimauchi, Hidetoshi

    2010-04-16

    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.

  4. Auger electron spectroscopy for the determination of sex and age related Ca/P ratio at different bone sites

    SciTech Connect (OSTI)

    Balatsoukas, Ioannis; Kourkoumelis, Nikolaos; Tzaphlidou, Margaret

    2010-10-15

    The Ca/P ratio of normal cortical and trabecular rat bone was measured by Auger electron spectroscopy (AES). Semiquantitative analysis was carried out using ratio techniques to draw conclusions on how age, sex and bone site affect the relative composition of calcium and phosphorus. Results show that Ca/P ratio is not sex dependent; quite the opposite, bone sites exhibit variations in elemental stoichiometry where femoral sections demonstrate higher Ca/P ratio than rear and front tibias. Age-related changes are more distinct for cortical bone in comparison with the trabecular bone. The latter's Ca/P ratio remains unaffected from all the parameters under study. This study confirms that AES is able to successfully quantify bone mineral main elements when certain critical points, related to the experimental conditions, are addressed effectively.

  5. Research Finds Vitamin D Deficiency Affects Bone Quality

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

    Research Finds Vitamin D Deficiency Affects Bone Quality Research Finds Vitamin D Deficiency Affects Bone Quality Print Wednesday, 30 April 2014 00:00 Vitamin D deficiency is a widespread medical condition that plays a major role in human bone health. Scientists know that a lack of vitamin D can cause bone diseases such as rickets and osteomalacia. Now a team of researchers working at the ALS has also found that vitamin D deficiency plays a significant role in the bone-aging process. Low levels

  6. Role of paraoxonase-1 in bone anabolic effects of parathyroid hormone in hyperlipidemic mice

    SciTech Connect (OSTI)

    Lu, Jinxiu; Cheng, Henry; Atti, Elisa; Shih, Diana M.; Demer, Linda L.; Tintut, Yin

    2013-02-01

    Highlights: ► Anabolic effects of PTH were tested in hyperlipidemic mice overexpressing PON1. ► Expression of antioxidant regulatory genes was induced in PON1 overexpression. ► Bone resorptive activity was reduced in PON1 overexpressing hyperlipidemic mice. ► PON1 restored responsiveness to intermittent PTH in bones of hyperlipidemic mice. -- Abstract: Hyperlipidemia blunts anabolic effects of intermittent parathyroid hormone (PTH) on cortical bone, and the responsiveness to PTH are restored in part by oral administration of the antioxidant ApoA-I mimetic peptide, D-4F. To evaluate the mechanism of this rescue, hyperlipidemic mice overexpressing the high-density lipoprotein-associated antioxidant enzyme, paraoxonase 1 (Ldlr{sup −/−}PON1{sup tg}) were generated, and daily PTH injections were administered to Ldlr{sup −/−}PON1{sup tg} and to littermate Ldlr{sup −/−} mice. Expression of bone regulatory genes was determined by realtime RT-qPCR, and cortical bone parameters of the femoral bones by micro-computed tomographic analyses. PTH-treated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTH receptor (PTH1R), activating transcription factor-4 (ATF4), and osteoprotegerin (OPG) in femoral cortical bone, as well as significantly greater cortical bone mineral content, thickness, and area in femoral diaphyses compared with untreated Ldlr{sup −/−}PON1{sup tg} mice. In contrast, in control mice (Ldlr{sup −/−}) without PON1 overexpression, PTH treatment did not induce these markers. Calvarial bone of PTH-treated Ldlr{sup −/−}PON1{sup tg} mice also had significantly greater expression of osteoblastic differentiation marker genes as well as BMP-2-target and Wnt-target genes. Untreated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTHR1 than untreated Ldlr{sup −/−} mice, whereas sclerostin expression was reduced. In femoral cortical bones, expression levels of transcription factors, Fox

  7. Permanent Cortical Blindness After Bronchial Artery Embolization

    SciTech Connect (OSTI)

    Doorn, Colette S. van De Boo, Diederick W.; Weersink, Els J. M.; Delden, Otto M. van Reekers, Jim A. Lienden, Krijn P. van

    2013-12-15

    A 35-year-old female with a known medical history of cystic fibrosis was admitted to our institution for massive hemoptysis. CTA depicted a hypertrophied bronchial artery to the right upper lobe and showed signs of recent bleeding at that location. Bronchial artery embolization (BAE) was performed with gelfoam slurry, because pronounced shunting to the pulmonary artery was present. Immediately after BAE, the patient developed bilateral cortical blindness. Control angiography showed an initially not opacified anastomosis between the embolized bronchial artery and the right subclavian artery, near to the origin of the right vertebral artery. Cessation of outflow in the bronchial circulation reversed the flow through the anastomosis and allowed for spill of embolization material into the posterior circulation. Unfortunately the cortical blindness presented was permanent.

  8. Research Finds Vitamin D Deficiency Affects Bone Quality

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

    Research Finds Vitamin D Deficiency Affects Bone Quality Print Vitamin D deficiency is a widespread medical condition that plays a major role in human bone health. Scientists know that a lack of vitamin D can cause bone diseases such as rickets and osteomalacia. Now a team of researchers working at the ALS has also found that vitamin D deficiency plays a significant role in the bone-aging process. Low levels of vitamin D, the "sunshine vitamin," have been previously linked to the

  9. Research Finds Vitamin D Deficiency Affects Bone Quality

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

    Research Finds Vitamin D Deficiency Affects Bone Quality Print Vitamin D deficiency is a widespread medical condition that plays a major role in human bone health. Scientists know that a lack of vitamin D can cause bone diseases such as rickets and osteomalacia. Now a team of researchers working at the ALS has also found that vitamin D deficiency plays a significant role in the bone-aging process. Low levels of vitamin D, the "sunshine vitamin," have been previously linked to the

  10. Research Finds Vitamin D Deficiency Affects Bone Quality

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

    Research Finds Vitamin D Deficiency Affects Bone Quality Print Vitamin D deficiency is a widespread medical condition that plays a major role in human bone health. Scientists know that a lack of vitamin D can cause bone diseases such as rickets and osteomalacia. Now a team of researchers working at the ALS has also found that vitamin D deficiency plays a significant role in the bone-aging process. Low levels of vitamin D, the "sunshine vitamin," have been previously linked to the

  11. Research Finds Vitamin D Deficiency Affects Bone Quality

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

    Research Finds Vitamin D Deficiency Affects Bone Quality Print Vitamin D deficiency is a widespread medical condition that plays a major role in human bone health. Scientists know that a lack of vitamin D can cause bone diseases such as rickets and osteomalacia. Now a team of researchers working at the ALS has also found that vitamin D deficiency plays a significant role in the bone-aging process. Low levels of vitamin D, the "sunshine vitamin," have been previously linked to the

  12. Research Finds Vitamin D Deficiency Affects Bone Quality

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

    Research Finds Vitamin D Deficiency Affects Bone Quality Print Vitamin D deficiency is a widespread medical condition that plays a major role in human bone health. Scientists know that a lack of vitamin D can cause bone diseases such as rickets and osteomalacia. Now a team of researchers working at the ALS has also found that vitamin D deficiency plays a significant role in the bone-aging process. Low levels of vitamin D, the "sunshine vitamin," have been previously linked to the

  13. Research Finds Vitamin D Deficiency Affects Bone Quality

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

    Research Finds Vitamin D Deficiency Affects Bone Quality Print Vitamin D deficiency is a widespread medical condition that plays a major role in human bone health. Scientists know that a lack of vitamin D can cause bone diseases such as rickets and osteomalacia. Now a team of researchers working at the ALS has also found that vitamin D deficiency plays a significant role in the bone-aging process. Low levels of vitamin D, the "sunshine vitamin," have been previously linked to the

  14. Morphometric Comparison of Clavicle Outlines from 3D Bone Scans and 2D Chest Radiographs: A Short-listing Tool to Assist Radiographic Identification of Human Skeletons

    SciTech Connect (OSTI)

    Stephan, Carl N.; Amidan, Brett G.; Trease, Harold E.; Guyomarch, Pierre; Pulsipher, Trenton C.; Byrd, John E.

    2014-03-01

    This paper describes a computerized clavicle identification system, primarily designed to resolve the identities of unaccounted for US soldiers who fought in the Korean War. Elliptical Fourier analysis is used to quantify the clavicle outline shape from skeletons and postero-anterior antemortem chest radiographs to rank individuals in terms of metric distance. Similar to leading fingerprint identification systems, shortlists of the top matching candidates are extracted for subsequent human visual assessment. Two independent tests of the computerized system using 17 field-recovered skeletons and 409 chest radiographs demonstrate that true positive matches are captured within the top 5% of the sample 75% of the time. These results are outstanding given the eroded state of some field-recovered skeletons and the faintness of the 1950’s photoflurographs. These methods enhance the capability to resolve several hundred cold cases for which little circumstantial information exists and current DNA and dental record technologies cannot be applied.

  15. Bone fragments a body can make

    SciTech Connect (OSTI)

    Stout, S.D.; Ross, L.M. Jr. )

    1991-05-01

    Data obtained from various analytical techniques applied to a number of small bone fragments recovered from a crime scene were used to provide evidence for the occurrence of a fatality. Microscopic and histomorphometric analyses confirmed that the fragments were from a human skull. X-ray microanalysis of darkened areas on the bone fragments revealed a chemical signature that matched the chemical signature of a shotgun pellet recovered at the scene of the crime. The above findings supported the deoxyribonucleic acid (DNA) fingerprint evidence which, along with other evidence, was used to convict a man for the murder of his wife, even though her body was never recovered.

  16. Composites structures for bone tissue reconstruction

    SciTech Connect (OSTI)

    Neto, W.; Santos, João; Avérous, L.; Schlatter, G.; Bretas, Rosario

    2015-05-22

    The search for new biomaterials in the bone reconstitution field is growing continuously as humane life expectation and bone fractures increase. For this purpose, composite materials with biodegradable polymers and hydroxyapatite (HA) have been used. A composite material formed by a film, nanofibers and HA has been made. Both, the films and the non-woven mats of nanofibers were formed by nanocomposites made of butylene adipate-co-terephthalate (PBAT) and HA. The techniques used to produce the films and nanofibers were spin coating and electrospinning, respectively. The composite production and morphology were evaluated. The composite showed an adequate morphology and fibers size to be used as scaffold for cell growth.

  17. Development of high strength hydroxyapatite for bone tissue regeneration using nanobioactive glass composites

    SciTech Connect (OSTI)

    Shrivastava, Pragya; Dalai, Sridhar; Vijayalakshmi, S.; Sudera, Prerna; Sivam, Santosh Param; Sharma, Pratibha

    2013-02-05

    With an increasing demand of biocompatible bone substitutes for the treatment of bone diseases and bone tissue regeneration, bioactive glass composites are being tested to improvise the osteoconductive as well as osteoinductive properties. Nanobioactive glass (nBG) composites, having composition of SiO{sub 2} 70 mol%, CaO 26 mol % and P{sub 2}O{sub 5} 4 mol% were prepared by Freeze drying method using PEG-PPG-PEG co-polymer. Polymer addition improves the mechanical strength and porosity of the scaffold of nBG. Nano Bioactive glass composites upon implantation undergo specific reactions leading to the formation of crystalline hydroxyapatite (HA). This is tested in vitro using Simulated Body Fluid (SBF). This high strength hydroxyapatite (HA) layer acts as osteoconductive in cellular environment, by acting as mineral base of bones, onto which new bone cells proliferate leading to new bone formation. Strength of the nBG composites as well as HA is in the range of cortical and cancellous bone, thus proving significant for bone tissue regeneration substitutes.

  18. Bone morphogenetic protein

    SciTech Connect (OSTI)

    Xiao Yongtao; Xiang Lixin; Shao Jianzhong

    2007-10-26

    Bone morphogenetic proteins (BMPs) are multi-functional growth factors belonging to the transforming growth factor-beta superfamily. It has been demonstrated that BMPs had been involved in the regulation of cell proliferation, survival, differentiation and apoptosis. However, their hallmark ability is that play a pivotal role in inducing bone, cartilage, ligament, and tendon formation at both heterotopic and orthotopic sites. In this review, we mainly concentrate on BMP structure, function, molecular signaling and potential medical application.

  19. Digital electronic bone growth stimulator

    DOE Patents [OSTI]

    Kronberg, James W.

    1995-01-01

    A device for stimulating bone tissue by applying a low level alternating current signal directly to the patient's skin. A crystal oscillator, a binary divider chain and digital logic gates are used to generate the desired waveforms that reproduce the natural electrical characteristics found in bone tissue needed for stimulating bone growth and treating osteoporosis. The device, powered by a battery, contains a switch allowing selection of the correct waveform for bone growth stimulation or osteoporosis treatment so that, when attached to the skin of the patient using standard skin contact electrodes, the correct signal is communicated to the underlying bone structures.

  20. Digital electronic bone growth stimulator

    DOE Patents [OSTI]

    Kronberg, J.W.

    1995-05-09

    A device is described for stimulating bone tissue by applying a low level alternating current signal directly to the patient`s skin. A crystal oscillator, a binary divider chain and digital logic gates are used to generate the desired waveforms that reproduce the natural electrical characteristics found in bone tissue needed for stimulating bone growth and treating osteoporosis. The device, powered by a battery, contains a switch allowing selection of the correct waveform for bone growth stimulation or osteoporosis treatment so that, when attached to the skin of the patient using standard skin contact electrodes, the correct signal is communicated to the underlying bone structures. 5 figs.

  1. Tenascin-W inhibits proliferation and differentiation of preosteoblasts during endochondral bone formation

    SciTech Connect (OSTI)

    Kimura, Hiroaki; Akiyama, Haruhiko . E-mail: hakiyama@kuhp.kyoto-u.ac.jp; Nakamura, Takashi; Crombrugghe, Benoit de

    2007-05-18

    We identified a cDNA encoding mouse Tenascin-W (TN-W) upregulated by bone morphogenetic protein (Bmp)2 in ATDC5 osteo-chondroprogenitors. In adult mice, TN-W was markedly expressed in bone. In mouse embryos, during endochondral bone formation TN-W was localized in perichondrium/periosteum, but not in trabecular and cortical bones. During bone fracture repair, cells in the newly formed perichondrium/periosteum surrounding the cartilaginous callus expressed TN-W. Furthermore, TN-W was detectable in perichondrium/periosteum of Runx2-null and Osterix-null embryos, indicating that TN-W is expressed in preosteoblasts. In CFU-F and -O cells, TN-W had no effect on initiation of osteogenesis of bone marrow cells, and in MC3T3-E1 osteoblastic cells TN-W inhibited cell proliferation and Col1a1 expression. In addition, TN-W suppressed canonical Wnt signaling which stimulates osteoblastic differentiation. Our results indicate that TN-W is a novel marker of preosteoblasts in early stage of osteogenesis, and that TN-W inhibits cell proliferation and differentiation of preosteoblasts mediated by canonical Wnt signaling.

  2. Relationship between alveolar bone measured by /sup 125/I absorptiometry with analysis of standardized radiographs: 2. Bjorn technique

    SciTech Connect (OSTI)

    Ortman, L.F.; McHenry, K.; Hausmann, E.

    1982-05-01

    The Bjorn technique is widely used in periodontal studies as a standardized measure of alveolar bone. Recent studies have demonstrated the feasibility of using /sup 125/I absorptiometry to measure bone mass. The purpose of this study was to compare /sup 125/I absorptiometry with the Bjorn technique in detecting small sequential losses of alveolary bone. Four periodontal-like defects of incrementally increasing size were produced in alveolar bone in the posterior segment of the maxilla of a human skull. An attempt was made to sequentially reduce the amount of bone in 10% increments until no bone remained, a through and through defect. The bone remaining at each step was measured using /sup 125/I absorptiometry. At each site the /sup 125/I absorptiometry measurements were made at the same location by fixing the photon source to a prefabricated precision-made occlusal splint. This site was just beneath the crest and midway between the borders of two adjacent teeth. Bone loss was also determined by the Bjorn technique. Standardized intraoral films were taken using a custom-fitted acrylic clutch, and bone measurements were made from the root apex to coronal height of the lamina dura. A comparison of the data indicates that: (1) in early bone loss, less than 30%, the Bjorn technique underestimates the amount of loss, and (2) in advanced bone loss, more than 60% the Bjorn technique overestimates it.

  3. An Orientation Distribution Function for Trabecular Bone

    SciTech Connect (OSTI)

    Lawrence Livermore National Laboratory

    2004-10-08

    We describe a new method for quantifying the orientation of trabecular bone from three-dimensional images. Trabecular lattices from five human vertebrae were decomposed into individual trabecular elements, and the orientation, mass, and thickness of each element were recorded. Continuous functions that described the total mass (M({var_phi},{theta})) and mean thickness ({tau}({var_phi},{theta})) of all trabeculae as a function of orientation were derived. The results were compared with experimental measurements of the elastic modulus in the three principal anatomic directions. A power law scaling relationship between the anisotropies in mass and elastic modulus was observed; the scaling exponent was 1.41 (R{sup 2} = 0.88). As expected, the preponderance of trabecular mass was oriented along the cranial-caudal direction; on average, there was 3.4 times more mass oriented vertically than horizontally. Moreover, the vertical trabeculae were 30% thicker, on average, than the horizontal trabeculae. The vertical trabecular thickness was inversely related to the connectivity (R{sup 2} = 0.70; p = 0.07), suggesting a possible organization into either few, thick trabeculae or many thin trabeculae. The method, which accounts for the mechanical connectedness of the lattice, provides a rapid way to both visualize and quantify the three-dimensional organization of trabecular bone.

  4. In vivo assessment of magnesium status in human body using accelerator-based neutron activation measurement of hands: A pilot study

    SciTech Connect (OSTI)

    Aslam; Pejovic-Milic, A.; McNeill, F. E.; Byun, S. H.; Prestwich, W. V.; Chettle, D. R.

    2008-02-15

    Magnesium (Mg) is an element essential for many enzymatic reactions in the human body. Various human and animal studies suggest that changes in Mg status are linked to diseases such as cardiac arrhythmia, coronary heart disease, hypertension, premenstrual syndrome, and diabetes mellitus. Thus, knowledge of Mg levels in the human body is needed. A direct measurement of human blood serum, which contains only 0.3% of the total body Mg, is generally used to infer information about the status of Mg in the body. However, in many clinical situations, Mg stored in large levels, for example in bones, muscles, and soft tissues, needs to be monitored either to evaluate the efficacy of a treatment or to study the progression of diseases associated with the deficiency of total body Mg. This work presents a feasibility study of a noninvasive, in vivo neutron activation analysis (IVNAA) technique using the {sup 26}Mg(n,{gamma}){sup 27}Mg reaction to measure Mg levels in human hands. The technique employs the McMaster University high beam current Tandetron accelerator hand irradiation facility and an array of eight NaI (T1) detectors arranged in a 4{pi} geometry for delayed counting of the 0.844 and 1.014 MeV gamma rays emitted when {sup 27}Mg decays in the irradiated hand. Mg determination in humans using IVNAA of hands has been demonstrated to be feasible, with effective doses as low as one-quarter of those delivered in chest x rays. The overall experimental uncertainty in the measurements is estimated to be approximately 5% (1{sigma}). The results are found to be in the range of the in vitro measurements reported for other cortical bones collected from different sites of the human skeleton, which confirms that this technique mainly provides a measure of the amount of Mg in hand bones. The average concentration of Mg determined in human hands is 10.96{+-}1.25 ({+-}1 SD) mg Mg/g Ca. The coefficient of variation (11%) observed in this study is comparable with or lower than several

  5. Positive modulator of bone morphogenic protein-2

    DOE Patents [OSTI]

    Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua; Takahashi, Kazuyuki

    2009-01-27

    Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

  6. Digital electronic bone growth stimulator

    DOE Patents [OSTI]

    Kronberg, J.W.

    1993-01-01

    The present invention relates to the electrical treatment of biological tissue. In particular, the present invention discloses a device that produces discrete electrical pulse trains for treating osteoporosis and accelerating bone growth. According to its major aspects and broadly stated, the present invention consists of an electrical circuit configuration capable of generating Bassett-type waveforms shown with alternative signals provide for the treatment of either fractured bones or osteoporosis. The signal generator comprises a quartz clock, an oscillator circuit, a binary divider chain, and a plurality of simple, digital logic gates. Signals are delivered efficiently, with little or no distortion, and uniformly distributed throughout the area of injury. Perferably, power is furnished by widely available and inexpensive radio batteries, needing replacement only once in several days. The present invention can be affixed to a medical cast without a great increase in either weight or bulk. Also, the disclosed stimulator can be used to treat osteoporosis or to strengthen a healing bone after the cast has been removed by attaching the device to the patient`s skin or clothing.

  7. Bioactive Glass Scaffolds for Bone Regeneration

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

    Bioactive Glass Scaffolds for Bone Regeneration Bioactive Glass Scaffolds for Bone Regeneration Print Wednesday, 28 September 2011 00:00 Natural materials are renowned for their unique combination of outstanding mechanical properties and exquisite microstructure. For example, bone, cork, and wood are porous biological materials with high specific stiffness (stiffness per unit weight) and specific strength. The outstanding mechanical properties of these materials are attributed to their

  8. Bioactive Glass Scaffolds for Bone Regeneration

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

    of ions from bioactive glasses reportedly activates the expression of osteogenic genes and stimulates bone growth, or angiogenesis. The ease and efficiency with which...

  9. Bioactive Glass Scaffolds for Bone Regeneration

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

    necessary to promote bone regeneration while substituting for, at least temporarily, the tissue by maintaining these loads in vivo. Porous metallic implants used for replacement...

  10. Radioimmunoassay of bone morphogenetic protein in serum: a tissue-specific parameter of bone metabolism

    SciTech Connect (OSTI)

    Urist, M.R.; Hudak, R.T.

    1984-05-01

    Bone morphogenetic protein (BMP), a paracrine agent inducing cartilage and bone cell differentiation, circulates in the blood and is detectable by BMP radioimmunoassay. Serum BMP levels are higher in growing children and patients with Paget's disease than in normal adults. These observations are interpreted as evidence of a BMP function in the physiology of bone in health and disease.

  11. Hydroxyapatite-binding peptides for bone growth and inhibition

    DOE Patents [OSTI]

    Bertozzi, Carolyn R.; Song, Jie; Lee, Seung-Wuk

    2011-09-20

    Hydroxyapatite (HA)-binding peptides are selected using combinatorial phage library display. Pseudo-repetitive consensus amino acid sequences possessing periodic hydroxyl side chains in every two or three amino acid sequences are obtained. These sequences resemble the (Gly-Pro-Hyp).sub.x repeat of human type I collagen, a major component of extracellular matrices of natural bone. A consistent presence of basic amino acid residues is also observed. The peptides are synthesized by the solid-phase synthetic method and then used for template-driven HA-mineralization. Microscopy reveal that the peptides template the growth of polycrystalline HA crystals .about.40 nm in size.

  12. Extraction and analysis of neuron firing signals from deep cortical video microscopy

    SciTech Connect (OSTI)

    Kerekes, Ryan A; Blundon, Jay

    2014-01-01

    We introduce a method for extracting and analyzing neuronal activity time signals from video of the cortex of a live animal. The signals correspond to the firing activity of individual cortical neurons. Activity signals are based on the changing fluorescence of calcium indicators in the cells over time. We propose a cell segmentation method that relies on a user-specified center point, from which the signal extraction method proceeds. A stabilization approach is used to reduce tissue motion in the video. The extracted signal is then processed to flatten the baseline and detect action potentials. We show results from applying the method to a cortical video of a live mouse.

  13. Bioactive Glass Scaffolds for Bone Regeneration

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

    Bioactive Glass Scaffolds for Bone Regeneration Print Natural materials are renowned for their unique combination of outstanding mechanical properties and exquisite microstructure. For example, bone, cork, and wood are porous biological materials with high specific stiffness (stiffness per unit weight) and specific strength. The outstanding mechanical properties of these materials are attributed to their anisotropic structures, which have optimized strength-to-density and stiffness-to-density

  14. Bioactive Glass Scaffolds for Bone Regeneration

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

    Bioactive Glass Scaffolds for Bone Regeneration Print Natural materials are renowned for their unique combination of outstanding mechanical properties and exquisite microstructure. For example, bone, cork, and wood are porous biological materials with high specific stiffness (stiffness per unit weight) and specific strength. The outstanding mechanical properties of these materials are attributed to their anisotropic structures, which have optimized strength-to-density and stiffness-to-density

  15. Bioactive Glass Scaffolds for Bone Regeneration

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

    Bioactive Glass Scaffolds for Bone Regeneration Print Natural materials are renowned for their unique combination of outstanding mechanical properties and exquisite microstructure. For example, bone, cork, and wood are porous biological materials with high specific stiffness (stiffness per unit weight) and specific strength. The outstanding mechanical properties of these materials are attributed to their anisotropic structures, which have optimized strength-to-density and stiffness-to-density

  16. Bioactive Glass Scaffolds for Bone Regeneration

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

    Bioactive Glass Scaffolds for Bone Regeneration Print Natural materials are renowned for their unique combination of outstanding mechanical properties and exquisite microstructure. For example, bone, cork, and wood are porous biological materials with high specific stiffness (stiffness per unit weight) and specific strength. The outstanding mechanical properties of these materials are attributed to their anisotropic structures, which have optimized strength-to-density and stiffness-to-density

  17. Bioactive Glass Scaffolds for Bone Regeneration

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

    Bioactive Glass Scaffolds for Bone Regeneration Print Natural materials are renowned for their unique combination of outstanding mechanical properties and exquisite microstructure. For example, bone, cork, and wood are porous biological materials with high specific stiffness (stiffness per unit weight) and specific strength. The outstanding mechanical properties of these materials are attributed to their anisotropic structures, which have optimized strength-to-density and stiffness-to-density

  18. Bioactive Glass Scaffolds for Bone Regeneration

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

    Bioactive Glass Scaffolds for Bone Regeneration Print Natural materials are renowned for their unique combination of outstanding mechanical properties and exquisite microstructure. For example, bone, cork, and wood are porous biological materials with high specific stiffness (stiffness per unit weight) and specific strength. The outstanding mechanical properties of these materials are attributed to their anisotropic structures, which have optimized strength-to-density and stiffness-to-density

  19. Bioactive Glass Scaffolds for Bone Regeneration

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

    Bioactive Glass Scaffolds for Bone Regeneration Print Natural materials are renowned for their unique combination of outstanding mechanical properties and exquisite microstructure. For example, bone, cork, and wood are porous biological materials with high specific stiffness (stiffness per unit weight) and specific strength. The outstanding mechanical properties of these materials are attributed to their anisotropic structures, which have optimized strength-to-density and stiffness-to-density

  20. The materials used in bone tissue engineering

    SciTech Connect (OSTI)

    Tereshchenko, V. P. Kirilova, I. A.; Sadovoy, M. A.; Larionov, P. M.

    2015-11-17

    Bone tissue engineering looking for an alternative solution to the problem of skeletal injuries. The method is based on the creation of tissue engineered bone tissue equivalent with stem cells, osteogenic factors, and scaffolds - the carriers of these cells. For production of tissue engineered bone equivalent is advisable to create scaffolds similar in composition to natural extracellular matrix of the bone. This will provide optimal conditions for the cells, and produce favorable physico-mechanical properties of the final construction. This review article gives an analysis of the most promising materials for the manufacture of cell scaffolds. Biodegradable synthetic polymers are the basis for the scaffold, but it alone cannot provide adequate physical and mechanical properties of the construction, and favorable conditions for the cells. Addition of natural polymers improves the strength characteristics and bioactivity of constructions. Of the inorganic compounds, to create cell scaffolds the most widely used calcium phosphates, which give the structure adequate stiffness and significantly increase its osteoinductive capacity. Signaling molecules do not affect the physico-mechanical properties of the scaffold, but beneficial effect is on the processes of adhesion, proliferation and differentiation of cells. Biodegradation of the materials will help to fulfill the main task of bone tissue engineering - the ability to replace synthetic construct by natural tissues that will restore the original anatomical integrity of the bone.

  1. Final Report for completed IPP Project:"Development of Plasma Ablation for Soft Tissue and Bone Surgery"

    SciTech Connect (OSTI)

    Brown, Ian

    2009-09-01

    ArthroCare is a medical device company that develops, manufactures, and markets an advanced surgical tool, a plasma electro-surgical system for cutting and removing tissue. The hand-held electrical discharge device produces plasma in a biocompatible conductive fluid and tissue to which it is applied during surgery. Its products allow surgeons to operate with increased precision and accuracy, limiting damage to surrounding tissue thereby reducing pain and speeding recovery for the patient. In the past, the design of ArthfoCare's plasma wands has been an empirical undertaking. One goal of this R&D program was to put the phenomena involved on a sound scientific footing, allowing optimization of existing plasma based electro-surgery system technology, and the design and manufacture of new and improved kinds of scalpels, in particular for the surgical cutting of bone. Another important related goal of the program was to develop, through an experimental approach, new plasma wand approaches to the cutting ('shaving') of hard bone tissue. The goals of the CRADA were accomplished - computer models were used to predict important parameters of the plasma discharge and the bone environment, and several different approaches to bone-shaving were developed and demonstrated. The primary goal of the project was to develop and demonstrate an atmospheric-pressure plasma tool that is suitable for surgical use for shaving bone in humans. This goal was accomplished, in fact with several different alternative plasma approaches. High bone ablation speeds were measured. The use of probes ('plasma wand' - the surgical tool) with moving active electrodes was also explored, and there are advantages to this method. Another important feature is that the newly-exposed bone surface have only a very thin necrosis layer; this feature was demonstrated. This CRADA has greatly advanced our understanding of bone removal by atmospheric pressure plasmas in liquid, and puts ArthroCare in a good position

  2. Research Finds Vitamin D Deficiency Affects Bone Quality

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

    the formation of new bone mass. In children, vitamin D deficiency can lead to rickets. In adults, vitamin D deficiency causes osteomalacia, a softening of the bones associated with...

  3. Prehistoric Animal Bones Found at Pantex | National Nuclear Security...

    National Nuclear Security Administration (NNSA)

    Home NNSA Blog Prehistoric Animal Bones Found at Pantex Prehistoric Animal Bones Found at Pantex Keck A sharp eye and a lot of luck led to an interesting discovery at Pantex ...

  4. ALSNews Vol. 311

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

    1 Print Irradiation Effects on Human Cortical Bone Fracture Behavior The role irradiation plays in high-exposure bone fracturing experiments, and how it affects the properties of bone tissue, are not fully understood. To better predict fracturing in bone, researchers must understand the role of sustained irradiation damage at different size scales within bone. Using synchrotron radiation microtomography at ALS Beamline 8.3.2, researchers investigated changes in crack path and toughening

  5. ALSNews Vol. 311

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

    1 ALSNews Vol. 311 Print Wednesday, 28 July 2010 00:00 Irradiation Effects on Human Cortical Bone Fracture Behavior The role irradiation plays in high-exposure bone fracturing experiments, and how it affects the properties of bone tissue, are not fully understood. To better predict fracturing in bone, researchers must understand the role of sustained irradiation damage at different size scales within bone. Using synchrotron radiation microtomography at ALS Beamline 8.3.2, researchers

  6. ALSNews Vol. 311

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

    1 Print Irradiation Effects on Human Cortical Bone Fracture Behavior The role irradiation plays in high-exposure bone fracturing experiments, and how it affects the properties of bone tissue, are not fully understood. To better predict fracturing in bone, researchers must understand the role of sustained irradiation damage at different size scales within bone. Using synchrotron radiation microtomography at ALS Beamline 8.3.2, researchers investigated changes in crack path and toughening

  7. ALSNews Vol. 311

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

    1 Print Irradiation Effects on Human Cortical Bone Fracture Behavior The role irradiation plays in high-exposure bone fracturing experiments, and how it affects the properties of bone tissue, are not fully understood. To better predict fracturing in bone, researchers must understand the role of sustained irradiation damage at different size scales within bone. Using synchrotron radiation microtomography at ALS Beamline 8.3.2, researchers investigated changes in crack path and toughening

  8. ALSNews Vol. 311

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

    1 Print Irradiation Effects on Human Cortical Bone Fracture Behavior The role irradiation plays in high-exposure bone fracturing experiments, and how it affects the properties of bone tissue, are not fully understood. To better predict fracturing in bone, researchers must understand the role of sustained irradiation damage at different size scales within bone. Using synchrotron radiation microtomography at ALS Beamline 8.3.2, researchers investigated changes in crack path and toughening

  9. ALSNews Vol. 311

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

    1 Print Irradiation Effects on Human Cortical Bone Fracture Behavior The role irradiation plays in high-exposure bone fracturing experiments, and how it affects the properties of bone tissue, are not fully understood. To better predict fracturing in bone, researchers must understand the role of sustained irradiation damage at different size scales within bone. Using synchrotron radiation microtomography at ALS Beamline 8.3.2, researchers investigated changes in crack path and toughening

  10. ALSNews Vol. 311

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

    1 Print Irradiation Effects on Human Cortical Bone Fracture Behavior The role irradiation plays in high-exposure bone fracturing experiments, and how it affects the properties of bone tissue, are not fully understood. To better predict fracturing in bone, researchers must understand the role of sustained irradiation damage at different size scales within bone. Using synchrotron radiation microtomography at ALS Beamline 8.3.2, researchers investigated changes in crack path and toughening

  11. The effects and mechanisms of clinorotation on proliferation and differentiation in bone marrow mesenchymal stem cells

    SciTech Connect (OSTI)

    Yan, Ming; Wang, Yongchun; Yang, Min; Liu, Yanwu; Qu, Bo; Ye, Zhengxu; Liang, Wei; Sun, Xiqing; Luo, Zhuojing

    2015-05-01

    Data from human and rodent studies have demonstrated that microgravity induces observed bone loss in real spaceflight or simulated experiments. The decrease of bone formation and block of maturation may play important roles in bone loss induced by microgravity. The aim of this study was to investigate the changes of proliferation and differentiation in bone marrow mesenchymal stem cells (BMSCs) induced by simulated microgravity and the mechanisms underlying it. We report here that clinorotation, a simulated model of microgravity, decreased proliferation and differentiation in BMSCs after exposure to 48 h simulated microgravity. The inhibited proliferation are related with blocking the cell cycle in G2/M and enhancing the apoptosis. While alterations of the osteoblast differentiation due to the decreased SATB2 expression induced by simulated microgravity in BMSCs. - Highlights: • Simulated microgravity inhibited proliferation and differentiation in BMSCs. • The decreased proliferation due to blocked cell cycle and enhanced the apoptosis. • The inhibited differentiation accounts for alteration of SATB2, Hoxa2 and Cbfa1.

  12. Bone scintigraphy in evaluating the viability of composite bone grafts revascularized by microvascular anastomoses, conventional autogenous bone grafts, and free non-revascularized periosteal grafts

    SciTech Connect (OSTI)

    Berggren, A.; Weiland, A.J.; Ostrup, L.T.

    1982-07-01

    Researchers studied the value of bone scintigraphy in the assessment of anastomotic patency and bone-cell viability in free bone grafts revascularized by microvascular anastomoses in twenty-seven dogs. The dogs were divided into three different groups, and scintigraphy was carried out using technetium-labeled methylene diphosphonate in composite bone grafts revascularized by microvascular anastomoses, conventional autogenous bone grafts, and periosteal grafts placed in different recipient beds. The viability of the grafts were evaluated by histological examination and fluorescence microscopy after triple labeling with oxytetracycline on the first postoperative day, alizarin complexone on the fourth postoperative day, and DCAF on the eleventh postoperative day. A positive scintiscan within the first week following surgery indicated patent microvascular anastomoses, and histological study and fluorescence microscopy confirmed that bone throughout the graft was viable. A positive scintiscan one week after surgery or later does not necessarily indicate microvascular patency or bone-cell survival, because new bone formed by creeping substitution on the surface of a dead bone graft can result in this finding.

  13. Simvastatin enhances bone morphogenetic protein receptor type II expression

    SciTech Connect (OSTI)

    Hu Hong; Sung, Arthur; Zhao, Guohua; Shi, Lingfang; Qiu Daoming; Nishimura, Toshihiko; Kao, Peter N. . E-mail: peterkao@stanford.edu

    2006-01-06

    Statins confer therapeutic benefits in systemic and pulmonary vascular diseases. Bone morphogenetic protein (BMP) receptors serve essential signaling functions in cardiovascular development and skeletal morphogenesis. Mutations in BMP receptor type II (BMPR2) are associated with human familial and idiopathic pulmonary arterial hypertension, and pathologic neointimal proliferation of vascular endothelial and smooth muscle cells within small pulmonary arteries. In severe experimental pulmonary hypertension, simvastatin reversed disease and conferred a 100% survival advantage. Here, modulation of BMPR2 gene expression by simvastatin is characterized in human embryonic kidney (HEK) 293T, pulmonary artery smooth muscle, and lung microvascular endothelial cells (HLMVECs). A 1.4 kb BMPR2 promoter containing Egr-1 binding sites confers reporter gene activation in 293T cells which is partially inhibited by simvastatin. Simvastatin enhances steady-state BMPR2 mRNA and protein expression in HLMVEC, through posttranscriptional mRNA stabilization. Simvastatin induction of BMPR2 expression may improve BMP-BMPR2 signaling thereby enhancing endothelial differentiation and function.

  14. Raman spectroscopy of the organic and mineral structure of bone grafts

    SciTech Connect (OSTI)

    Timchenko, E V; Timchenko, P E; Taskina, L A; Volova, L T; Ponomareva, Yu V

    2014-07-31

    We report the results of experimental Raman spectroscopy of donor bone samples (rat, rabbit and human) with varying degrees of mineralisation. Raman spectra are obtained for the Raman bands of 950 – 962 cm{sup -1} (PO{sub 4}){sup 3-}, 1065 – 1070 cm{sup -1} (CO{sub 3}){sup 2-} and 1665 cm{sup -1} (amide I). In demineralised bone, a sharp (98%) decrease in the intensities of 950 – 962 and 1065 – 1070 cm{sup -1} bands is observed, which is accompanied by the emergence of the 1079 – 1090 cm{sup -1} band corresponding to the hydrated amorphous state CO{sub 3}{sup -3}. (laser biophotonics)

  15. Modeling aspects of human memory for scientific study.

    SciTech Connect (OSTI)

    Caudell, Thomas P.; Watson, Patrick; McDaniel, Mark A.; Eichenbaum, Howard B.; Cohen, Neal J.; Vineyard, Craig Michael; Taylor, Shawn Ellis; Bernard, Michael Lewis; Morrow, James Dan; Verzi, Stephen J.

    2009-10-01

    Working with leading experts in the field of cognitive neuroscience and computational intelligence, SNL has developed a computational architecture that represents neurocognitive mechanisms associated with how humans remember experiences in their past. The architecture represents how knowledge is organized and updated through information from individual experiences (episodes) via the cortical-hippocampal declarative memory system. We compared the simulated behavioral characteristics with those of humans measured under well established experimental standards, controlling for unmodeled aspects of human processing, such as perception. We used this knowledge to create robust simulations of & human memory behaviors that should help move the scientific community closer to understanding how humans remember information. These behaviors were experimentally validated against actual human subjects, which was published. An important outcome of the validation process will be the joining of specific experimental testing procedures from the field of neuroscience with computational representations from the field of cognitive modeling and simulation.

  16. Human Resources | Argonne National Laboratory

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

    Human Resources

  17. Protocadherin-7 induces bone metastasis of breast cancer

    SciTech Connect (OSTI)

    Li, Ai-Min; Tian, Ai-Xian; Zhang, Rui-Xue; Ge, Jie; Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin ; Sun, Xuan; Cao, Xu-Chen; Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin

    2013-07-05

    Highlights: PCDH7 is overexpression in high bone metastatic MDA-MB-231 cells. PCDH7 is up-regulation in bone metastatic breast cancer tissues. Suppression of PCDH7 inhibits cell proliferation, migration, and invasion in vitro. PCDH7 induces breast cancer bone metastasis in vivo. -- Abstract: Breast cancer had a propensity to metastasize to bone, resulting in serious skeletal complications associated with poor outcome. Previous study showed that Protocadherin-7 (PCDH7) play an important role in brain metastatic breast cancer, however, the role of PCDH7 in bone metastatic breast cancer has never been explored. In the present study, we found that PCDH7 expression was up-regulation in bone metastatic breast cancer tissues by real-time PCR and immunohistochemistry assays. Furthermore, suppression of PCDH7 inhibits breast cancer cell proliferation, migration, and invasion in vitro by MTT, scratch, and transwell assays. Most importantly, overexpression of PCDH7 promotes breast cancer cell proliferation and invasion in vitro, and formation of bone metastasis in vivo. These data provide an important insight into the role of PCDH7 in bone metastasis of breast cancer.

  18. DISCOVERY AND RESEARCH ON JIAHU BONE FLUTES IN WUYANG, CHINA.

    SciTech Connect (OSTI)

    JUZHONG, Z.; HARBOTTLE, G.; XINGHUA, X.; CHANGSUI, W.

    2000-11-01

    The site of Jiahu is located in Jiahu village, Wuyang County, Henan province, on the Western edge of the broad plain of Huanhuaihai. On its north the site borders the Sha River, in the upper reaches of the Huai River; its latitude is 33{degree} 36 minutes North, longitude 113{degree} 40 minutes East, and it is 67.5 meters above sea level. Between 1983 and 1987, the Henan Cultural Relics and Archaeology Institute carried out six campaigns of excavation here, revealing an area of 2400 square meters. Except for the trial excavation in the spring of 1983, Zhang Juzhong has been in charge of all the excavations. In early May 1986, while excavating tomb 78, Zhang Juzhong and Yang Zhenwei first discovered two funerary bone flutes. They soon found other, similar bone flutes in tombs 73, 94 and 121 respectively. Mr. Zhang's attention was instantly focused on these remarkable finds. In the campaign of autumn 1986, one or two more bone flutes were discovered in each of tombs 233,273, 263 and 270. Finally, in the spring of 1987, again one or two bone flutes were found in each of the tombs 282, 363,341,411,344 and 387. Up to the end of excavation in June 1987, altogether 25 bone flutes had been found, of which 17 were complete or almost complete, 6 broken or fragmentary and 2 were half-finished examples. Among the 17 complete bone flutes, there were 14 having seven holes, one five-hole, one six-hole and one eight-hole bone flute. In particular, the bone flute M282:20 was exquisitely made, and complete. Zhang Juzhong, the discoverer of the bone flutes, researcher Pei Mingxiang, the. ex-director of the division, who came to the digging site to see the progress of the work, and their coworkers were all understandably very excited.

  19. The effects of low environmental cadmium exposure on bone density

    SciTech Connect (OSTI)

    Trzcinka-Ochocka, M.; Jakubowski, M.; Szymczak, W.; Janasik, B.; Brodzka, R.

    2010-04-15

    Recent epidemiological data indicate that low environmental exposure to cadmium, as shown by cadmium body burden (Cd-U), is associated with renal dysfunction as well as an increased risk of cadmium-induced bone disorders. The present study was designed to assess the effects of low environmental cadmium exposure, at the level sufficient to induce kidney damage, on bone metabolism and mineral density (BMD). The project was conducted in the area contaminated with cadmium, nearby a zinc smelter located in the region of Poland where heavy industry prevails. The study population comprised 170 women (mean age=39.7; 18-70 years) and 100 men (mean age=31.9; 18-76 years). Urinary and blood cadmium and the markers of renal tubular dysfunction ({beta}{sub 2}M-U RBP, NAG), glomerular dysfunction (Alb-U and {beta}{sub 2}M-S) and bone metabolism markers (BAP-S, CTX-S) as well as forearm BMD, were measured. The results of this study based on simple dose-effect analysis showed the relationship between increasing cadmium concentrations and an increased excretion of renal dysfunction markers and decreasing bone density. However, the results of the multivariate analysis did not indicate the association between exposure to cadmium and decrease in bone density. They showed that the most important factors that have impact on bone density are body weight and age in the female subjects and body weight and calcium excretion in males. Our investigation revealed that the excretion of low molecular weight proteins occurred at a lower level of cadmium exposure than the possible loss of bone mass. It seems that renal tubular markers are the most sensitive and significant indicators of early health effects of cadmium intoxication in the general population. The correlation of urinary cadmium concentration with markers of kidney dysfunction was observed in the absence of significant correlations with bone effects. Our findings did not indicate any effects of environmental cadmium exposure on bone

  20. Processing of hydroxylapatite coatings on titanium alloy bone prostheses

    DOE Patents [OSTI]

    Nastasi, M.A.; Levine, T.E.; Mayer, J.W.; Pizziconi, V.B.

    1998-10-06

    Processing of hydroxylapatite sol-gel films on titanium alloy bone prostheses. A method utilizing non-line-of-sight ion beam implantation and/or rapid thermal processing to provide improved bonding of layers of hydroxylapatite to titanium alloy substrates while encouraging bone ingrowth into the hydroxylapatite layers located away from the substrate, is described for the fabrication of prostheses. The first layer of hydroxylapatite is mixed into the substrate by the ions or rapidly thermally annealed, while subsequent layers are heat treated or densified using ion implantation to form layers of decreasing density and larger crystallization, with the outermost layers being suitable for bone ingrowth.

  1. Processing of hydroxylapatite coatings on titanium alloy bone prostheses

    DOE Patents [OSTI]

    Nastasi, Michael A.; Levine, Timothy E.; Mayer, James W.; Pizziconi, Vincent B.

    1998-01-01

    Processing of hydroxylapatite sol-gel films on titanium alloy bone prostheses. A method utilizing non-line-of-sight ion beam implantation and/or rapid thermal processing to provide improved bonding of layers of hydroxylapatite to titanium alloy substrates while encouraging bone ingrowth into the hydroxylapatite layers located away from the substrate, is described for the fabrication of prostheses. The first layer of hydroxylapatite is mixed into the substrate by the ions or rapidly thermally annealed, while subsequent layers are heat treated or densified using ion implantation to form layers of decreasing density and larger crystallization, with the outermost layers being suitable for bone ingrowth.

  2. Bone marrow-derived osteoblast progenitor cells in circulating blood contribute to ectopic bone formation in mice

    SciTech Connect (OSTI)

    Otsuru, Satoru; Tamai, Katsuto . E-mail: tamai@gts.med.osaka-u.ac.jp; Yamazaki, Takehiko; Yoshikawa, Hideki; Kaneda, Yasufumi

    2007-03-09

    Recent studies have suggested the existence of osteoblastic cells in the circulation, but the origin and role of these cells in vivo are not clear. Here, we examined how these cells contribute to osteogenesis in a bone morphogenetic protein (BMP)-induced model of ectopic bone formation. Following lethal dose-irradiation and subsequent green fluorescent protein-transgenic bone marrow cell-transplantation (GFP-BMT) in mice, a BMP-2-containing collagen pellet was implanted into muscle. Three weeks later, a significant number of GFP-positive osteoblastic cells were present in the newly generated ectopic bone. Moreover, peripheral blood mononuclear cells (PBMNCs) from the BMP-2-implanted mouse were then shown to include osteoblast progenitor cells (OPCs) in culture. Passive transfer of the PBMNCs isolated from the BMP-2-implanted GFP-mouse to the BMP-2-implanted nude mouse led to GFP-positive osteoblast accumulation in the ectopic bone. These data provide new insight into the mechanism of ectopic bone formation involving bone marrow-derived OPCs in circulating blood.

  3. Trace rare earth element analysis of IAEA hair (HH-1), animal bone (H-5) and other biological standards by radiochemical neutron activation

    SciTech Connect (OSTI)

    Lepel, E.A.; Laul, J.C.

    1986-03-01

    A radiochemical neutron activation analysis using a rare earth group separation scheme has been used to measure ultratrace levels of rare earth elements (REE) in IAEA Human Hair (HH-1), IAEA Animal Bone (H-5), NBS Bovine Liver (SRM 1577), and NBS Orchard Leaf (SRM 1571) standards. The REE concentrations in Human Hair and Animal Bone range from 10/sup -8/g/g to 10/sup -11/g/g and their chondritic normalized REE patterns show a negative Eu anomaly and follow as a smooth function of the REE ionic radii. The REE patterns for NBS Bovine Liver and Orchard Leaf are identical except that their concentrations are higher. The similarity among the REE patterns suggest that the REE do not appear to be fractionated during the intake of biological materials by animals or humans. 14 refs., 3 figs., 2 tabs.

  4. The bones of the Milky Way

    SciTech Connect (OSTI)

    Goodman, Alyssa A.; Beaumont, Christopher N. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Alves, Joo [University of Vienna, 1180 Vienna (Austria); Benjamin, Robert A. [University of Wisconsin-Whitewater, Whitewater, WI 53190 (United States); Borkin, Michelle A. [Harvard University, Cambridge, MA 02138 (United States); Burkert, Andreas [University of Munich, Munich (Germany); Dame, Thomas M. [Smithsonian Astrophysical Observatory, Cambridge, MA 02138 (United States); Jackson, James [Boston University, Boston, MA 02215 (United States); Kauffmann, Jens [California Institute of Technology, Pasadena, CA 91125 (United States); Robitaille, Thomas [Max Planck Institute for Astronomy, Heidelberg (Germany); Smith, Rowan J. [Institut fr Theoretische Astrophysik, Zentrum fr Astronomie der Universit Heidelberg, Heidelberg (Germany)

    2014-12-10

    The very long and thin infrared dark cloud 'Nessie' is even longer than had been previously claimed, and an analysis of its Galactic location suggests that it lies directly in the Milky Way's mid-plane, tracing out a highly elongated bone-like feature within the prominent Scutum-Centaurus spiral arm. Re-analysis of mid-infrared imagery from the Spitzer Space Telescope shows that this infrared dark cloud (IRDC) is at least two and possibly as many as five times longer than had originally been claimed by Nessie's discoverers; its aspect ratio is therefore at least 300:1 and possibly as large as 800:1. A careful accounting for both the Sun's offset from the Galactic plane (?25 pc) and the Galactic center's offset from the (l{sup II} , b{sup II} ) = (0, 0) position shows that the latitude of the true Galactic mid-plane at the 3.1 kpc distance to the Scutum-Centaurus Arm is not b = 0, but instead closer to b = 0.4, which is the latitude of Nessie to within a few parsecs. An analysis of the radial velocities of low-density (CO) and high-density (NH{sub 3}) gas associated with the Nessie dust feature suggests that Nessie runs along the Scutum-Centaurus Arm in position-position-velocity space, which means it likely forms a dense 'spine' of the arm in real space as well. The Scutum-Centaurus Arm is the closest major spiral arm to the Sun toward the inner Galaxy, and, at the longitude of Nessie, it is almost perpendicular to our line of sight, making Nessie the easiest feature to see as a shadow elongated along the Galactic plane from our location. Future high-resolution dust mapping and molecular line observations of the harder-to-find Galactic 'bones' should allow us to exploit the Sun's position above the plane to gain a (very foreshortened) view 'from above' the Milky Way's structure.

  5. Ectopic bone formation and chondrodysplasia in transgenic mice carrying the rat C3(1)/T{sub AG} fusion gene

    SciTech Connect (OSTI)

    Green, J.E.; Maroulakou, I.G.; Anver, M.

    1994-09-01

    Transgenic mice expressing the SV40 large T-antigen (T{sup AG}) under the regultory control of the hormone-responsive rat C3(1) prostatein promoter develop unusual bone and cartilage lesions, as well as ectopic bone and cartilage formation. Two lines of transgenic animals have been propagated in which the expression of the transgene in chondrocytes results in a mild to moderate generalized disorganization of cartilage growth which appears to affect multiple tissues, including the trachea, ear pinna and articular cartilage. The epiphyseal plates are also affected with normal architecture of the zones of proliferation and maturation, but marked elongation of the zone of hypertrophy. Immunocytochemistry demonstrates that expression of T{sup AG} is limited to the zone of hypertropny in the epiphyseal plates, suggesting that the chondrocytes become hormone-responsive at this particular stage of differentiation. Normal mineralization and trabecular formation in long bone appears to occur. Ectopic bone and cartilage formation occurs in the foot pads of the fore- and hind- feet over the course of several months. This is preceded by proliferation of sweat gland epithelial cells followed by the appearance of nodules of cartilage and bone. The nodules are closely associated with proliferating epithelium but are not contiguous with bony structures normally found in the feet. The roles of BMP`s, growth factors, oncogenes and hormones in the development of these lesions will be presented. These transgenic animals may provide new insights into hormone-responsiveness of chondrocytes, as well as factors involved in the processes of bone and cartilage differentiation and growth. These transgenic animals may serve as a useful model for human heterotopic bone formation.

  6. On the mechanistic origins of toughness in bone

    SciTech Connect (OSTI)

    Launey, Maximilien E.; Buehler, Markus J.; Ritchie, Robert O.

    2009-10-07

    One of the most intriguing protein materials found in Nature is bone, a material composed out of assemblies of tropocollagen molecules and tiny hydroxyapatite mineral crystals, forming an extremely tough, yet lightweight, adaptive and multi-functional material. Bone has evolved to provide structural support to organisms, and therefore, its mechanical properties are of great physiological relevance. In this article, we review the structure and properties of bone, focusing on mechanical deformation and fracture behavior from the perspective of the multi-dimensional hierarchical nature of its structure. In fact, bone derives its resistance to fracture with a multitude of deformation and toughening mechanisms at many of these size-scales, ranging from the nanoscale structure of its protein molecules to its macroscopic physiological scale.

  7. Compact biomedical pulsed signal generator for bone tissue stimulation

    DOE Patents [OSTI]

    Kronberg, J.W.

    1993-06-08

    An apparatus for stimulating bone tissue for stimulating bone growth or treating osteoporosis by applying directly to the skin of the patient an alternating current electrical signal comprising wave forms known to simulate the piezoelectric constituents in bone. The apparatus may, by moving a switch, stimulate bone growth or treat osteoporosis, as desired. Based on low-power CMOS technology and enclosed in a moisture-resistant case shaped to fit comfortably, two astable multivibrators produce the desired waveforms. The amplitude, pulse width and pulse frequency, and the subpulse width and subpulse frequency of the waveforms are adjustable. The apparatus, preferably powered by a standard 9-volt battery, includes signal amplitude sensors and warning signals indicate an output is being produced and the battery needs to be replaced.

  8. Compact biomedical pulsed signal generator for bone tissue stimulation

    DOE Patents [OSTI]

    Kronberg, James W.

    1993-01-01

    An apparatus for stimulating bone tissue for stimulating bone growth or treating osteoporosis by applying directly to the skin of the patient an alternating current electrical signal comprising wave forms known to simulate the piezoelectric constituents in bone. The apparatus may, by moving a switch, stimulate bone growth or treat osteoporosis, as desired. Based on low-power CMOS technology and enclosed in a moisture-resistant case shaped to fit comfortably, two astable multivibrators produce the desired waveforms. The amplitude, pulse width and pulse frequency, and the subpulse width and subpulse frequency of the waveforms are adjustable. The apparatus, preferably powered by a standard 9-volt battery, includes signal amplitude sensors and warning signals indicate an output is being produced and the battery needs to be replaced.

  9. PDGFBB promotes PDGFR{alpha}-positive cell migration into artificial bone in vivo

    SciTech Connect (OSTI)

    Yoshida, Shigeyuki; Center for Human Metabolomic Systems Biology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 ; Iwasaki, Ryotaro; Kawana, Hiromasa; Miyauchi, Yoshiteru; Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582; Department of Integrated Bone Metabolism and Immunology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 ; Hoshi, Hiroko; Miyamoto, Hiroya; Mori, Tomoaki; Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 ; Kanagawa, Hiroya; Katsuyama, Eri; Fujie, Atsuhiro; Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 ; Hao, Wu; and others

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer We examined effects of PDGFBB in PDGFR{alpha} positive cell migration in artificial bones. Black-Right-Pointing-Pointer PDGFBB was not expressed in osteoblastic cells but was expressed in peripheral blood cells. Black-Right-Pointing-Pointer PDGFBB promoted PDGFR{alpha} positive cell migration into artificial bones but not osteoblast proliferation. Black-Right-Pointing-Pointer PDGFBB did not inhibit osteoblastogenesis. -- Abstract: Bone defects caused by traumatic bone loss or tumor dissection are now treated with auto- or allo-bone graft, and also occasionally by artificial bone transplantation, particularly in the case of large bone defects. However, artificial bones often exhibit poor affinity to host bones followed by bony union failure. Thus therapies combining artificial bones with growth factors have been sought. Here we report that platelet derived growth factor bb (PDGFBB) promotes a significant increase in migration of PDGF receptor {alpha} (PDGFR{alpha})-positive mesenchymal stem cells/pre-osteoblastic cells into artificial bone in vivo. Growth factors such as transforming growth factor beta (TGF{beta}) and hepatocyte growth factor (HGF) reportedly inhibit osteoblast differentiation; however, PDGFBB did not exhibit such inhibitory effects and in fact stimulated osteoblast differentiation in vitro, suggesting that combining artificial bones with PDGFBB treatment could promote host cell migration into artificial bones without inhibiting osteoblastogenesis.

  10. Harmine promotes osteoblast differentiation through bone morphogenetic protein signaling

    SciTech Connect (OSTI)

    Yonezawa, Takayuki; Lee, Ji-Won; Hibino, Ayaka; Asai, Midori; Hojo, Hironori; Cha, Byung-Yoon; Teruya, Toshiaki; Nagai, Kazuo; Chung, Ung-Il; Yagasaki, Kazumi; and others

    2011-06-03

    Highlights: {yields} Harmine promotes the activity and mRNA expression of ALP. {yields} Harmine enhances the expressions of osteocalcin mRNA and protein. {yields} Harmine induces osteoblastic mineralization. {yields} Harmine upregulates the mRNA expressions of BMPs, Runx2 and Osterix. {yields} BMP signaling pathways are involved in the actions of harmine. -- Abstract: Bone mass is regulated by osteoblast-mediated bone formation and osteoclast-mediated bone resorption. We previously reported that harmine, a {beta}-carboline alkaloid, inhibits osteoclast differentiation and bone resorption in vitro and in vivo. In this study, we investigated the effects of harmine on osteoblast proliferation, differentiation and mineralization. Harmine promoted alkaline phosphatase (ALP) activity in MC3T3-E1 cells without affecting their proliferation. Harmine also increased the mRNA expressions of the osteoblast marker genes ALP and Osteocalcin. Furthermore, the mineralization of MC3T3-E1 cells was enhanced by treatment with harmine. Harmine also induced osteoblast differentiation in primary calvarial osteoblasts and mesenchymal stem cell line C3H10T1/2 cells. Structure-activity relationship studies using harmine-related {beta}-carboline alkaloids revealed that the C3-C4 double bond and 7-hydroxy or 7-methoxy group of harmine were important for its osteogenic activity. The bone morphogenetic protein (BMP) antagonist noggin and its receptor kinase inhibitors dorsomorphin and LDN-193189 attenuated harmine-promoted ALP activity. In addition, harmine increased the mRNA expressions of Bmp-2, Bmp-4, Bmp-6, Bmp-7 and its target gene Id1. Harmine also enhanced the mRNA expressions of Runx2 and Osterix, which are key transcription factors in osteoblast differentiation. Furthermore, BMP-responsive and Runx2-responsive reporters were activated by harmine treatment. Taken together, these results indicate that harmine enhances osteoblast differentiation probably by inducing the expressions of

  11. 3D View Inside the Skeleton with X-ray Microscopy: Imaging Bone...

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

    understanding of healthy bone tissue and the changes that occur with aging and disease. ... imaging experiments of bone using the transmission x-ray microscope (TXM) on SSRL beam ...

  12. Metastatic prostatic pulmonary nodules with normal bone image

    SciTech Connect (OSTI)

    Petras, A.F.; Wollett, F.C.

    1983-11-01

    Asymptomatic prostatic caricnoma presented as multiple bilateral pulmonary modules in a patient without any evidence of skeletal involvement by normal bone image. Percutaneous biopsy provided the initial clue to diagnosis. The authors recommend that asymptomatic prostatic carcinoma be included in the differential diagnosis of pulmonary nodules, even when there is no evidence of skeletal metastasis.

  13. Partial growth plate closure: apex view on bone scan

    SciTech Connect (OSTI)

    Howman-Giles, R.; Trochei, M.; Yeates, K.; Middleton, R.; Barrett, I.; Scougall, J.; Whiteway, D.

    1985-01-01

    A new technique of using /sup 99m/Tc bone scan to assess partial closure of the growth plate is described. The site and degree of osseous fusion can be obtained by using the apex view. The technique has the potential of assessing serially the growth of a plate before and after surgery.

  14. Celebrating Black History Month with DOE's Sheri Bone

    Broader source: Energy.gov [DOE]

    Throughout the month of February, we're introducing some remarkable African Americans who are working to advance the President's clean energy agenda and help the Department of Energy achieve its mission. This week we're profiling Sheri Bone who is Senior Project Director, Office of Nuclear Materials Integration, National Nuclear Security Administration.

  15. Bone morphogenetic protein-induced cartilage development in tissue culture

    SciTech Connect (OSTI)

    Sato, K.; Urist, M.R.

    1984-03-01

    Outgrowths of mesenchyme-type cells from explants of allogeneic rat muscle onto a substratum of bone matrix containing bone morphogenetic protein (BMP) differentiate into cartilage. When BMP is chemically extracted from the bone matrix, the explanted cells develop only into fibrous tissue. When exogenous bovine BMP is introduced into the culture medium, either as a microsuspension or as a layer of particles between the matrix and the muscle cell tissue, cartilage develops at the interface between the matrix and the mesenchymal cell outgrowth. The chondrogenetic response is induced by as little as 2 micrograms of BMP; the optimum dose is 10 micrograms/40 mg (wet weight) of explant. The endogenous BMP equivalent for a comparable chondrogenetic response is about 0.6 micrograms/mg of allogeneic matrix. The minimum time for transfer of BMP to mesenchymal cell receptors is 1.0 hour, adequate time is 2.5 hours, and optimum time is approximately 5.0 hours. Measured in terms of incorporation of /sup 3/H-thymidine into DNA and of /sup 35/S sulfate into glycosaminoglycan, there is a latent period of one to three days preceeding the differentiation of mesenchyme-type cells into cartilage. During this latent period BMP-modulated mesenchymal cells disaggregate, migrate, reaggregate, and proliferate on new surfaces and constitute the morphogenetic phase of bone development. By the fourth day cells simultaneously undergo mitotic division, synthesize extracellular cartilage matrix, and establish the cytodifferentiation phase of development.

  16. Bone regeneration by implantation of adipose-derived stromal cells expressing BMP-2

    SciTech Connect (OSTI)

    Li Huiwu; Dai Kerong . E-mail: krdai@163.com; Tang Tingting; Zhang Xiaoling; Yan Mengning; Lou Jueren

    2007-05-18

    In this study, we reported that the adipose-derived stromal cells (ADSCs) genetically modified by bone morphogenetic protein 2 (BMP-2) healed critical-sized canine ulnar bone defects. First, the osteogenic and adipogenic differentiation potential of the ADSCs derived from canine adipose tissue were demonstrated. And then the cells were modified by the BMP-2 gene and the expression and bone-induction ability of BMP-2 were identified. Finally, the cells modified by BMP-2 gene were applied to a {beta}-tricalcium phosphate (TCP) carrier and implanted into ulnar bone defects in the canine model. After 16 weeks, radiographic, histological, and histomorphometry analysis showed that ADSCs modified by BMP-2 gene produced a significant increase of newly formed bone area and healed or partly healed all of the bone defects. We conclude that ADSCs modified by the BMP-2 gene can enhance the repair of critical-sized bone defects in large animals.

  17. High fat diet promotes achievement of peak bone mass in young rats

    SciTech Connect (OSTI)

    Malvi, Parmanand; Piprode, Vikrant; Chaube, Balkrishna; Pote, Satish T.; Mittal, Monika; Chattopadhyay, Naibedya; Wani, Mohan R.; Bhat, Manoj Kumar

    2014-12-05

    Highlights: • High fat diet helps in achieving peak bone mass at younger age. • Shifting from high fat to normal diet normalizes obese parameters. • Bone parameters are sustained even after withdrawal of high fat diet. - Abstract: The relationship between obesity and bone is complex. Epidemiological studies demonstrate positive as well as negative correlation between obesity and bone health. In the present study, we investigated the impact of high fat diet-induced obesity on peak bone mass. After 9 months of feeding young rats with high fat diet, we observed obesity phenotype in rats with increased body weight, fat mass, serum triglycerides and cholesterol. There were significant increases in serum total alkaline phosphatase, bone mineral density and bone mineral content. By micro-computed tomography (μ-CT), we observed a trend of better trabecular bones with respect to their microarchitecture and geometry. This indicated that high fat diet helps in achieving peak bone mass and microstructure at younger age. We subsequently shifted rats from high fat diet to normal diet for 6 months and evaluated bone/obesity parameters. It was observed that after shifting rats from high fat diet to normal diet, fat mass, serum triglycerides and cholesterol were significantly decreased. Interestingly, the gain in bone mineral density, bone mineral content and trabecular bone parameters by HFD was retained even after body weight and obesity were normalized. These results suggest that fat rich diet during growth could accelerate achievement of peak bone mass that is sustainable even after withdrawal of high fat diet.

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

    SciTech Connect (OSTI)

    Rodrguez-Fuentes, Nayeli; Rodrguez-Hernndez, Ana G.; Enrquez-Jimnez, Juana; Alcntara-Quintana, Luz E.; Fuentes-Mera, Lizeth; Pia-Barba, Mara C.; Zepeda-Rodrguez, Armando; and others

    2013-05-10

    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.

  19. Calcium silicate ceramic scaffolds toughened with hydroxyapatite whiskers for bone tissue engineering

    SciTech Connect (OSTI)

    Feng, Pei; Wei, Pingpin; Li, Pengjian; Gao, Chengde; Shuai, Cijun; Peng, Shuping

    2014-11-15

    Calcium silicate possessed excellent biocompatibility, bioactivity and degradability, while the high brittleness limited its application in load-bearing sites. Hydroxyapatite whiskers ranging from 0 to 30 wt.% were incorporated into the calcium silicate matrix to improve the strength and fracture resistance. Porous scaffolds were fabricated by selective laser sintering. The effects of hydroxyapatite whiskers on the mechanical properties and toughening mechanisms were investigated. The results showed that the scaffolds had a uniform and continuous inner network with the pore size ranging between 0.5 mm and 0.8 mm. The mechanical properties were enhanced with increasing hydroxyapatite whiskers, reached a maximum at 20 wt.% (compressive strength: 27.28 MPa, compressive Young's modulus: 156.2 MPa, flexural strength: 15.64 MPa and fracture toughness: 1.43 MPa·m{sup 1/2}) and then decreased by addition of more hydroxyapatite whiskers. The improvement of mechanical properties was due to whisker pull-out, crack deflection and crack bridging. Moreover, the degradation rate decreased with the increase of hydroxyapatite whisker content. A layer of bone-like apatite was formed on the scaffold surfaces after being soaked in simulated body fluid. Human osteoblast-like MG-63 cells spread well on the scaffolds and proliferated with increasing culture time. These findings suggested that the calcium silicate scaffolds reinforced with hydroxyapatite whiskers showed great potential for bone regeneration and tissue engineering applications. - Highlights: • HA whiskers were incorporated into CS to improve the properties. • The scaffolds were successfully fabricated by SLS. • Toughening mechanisms was whisker pull-out, crack deflection and bridging. • The scaffolds showed excellent apatite forming ability.

  20. Archaeopteryx Feathers and Bone Chemistry Fully Revealed via Synchrotron

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

    Imaging Archaeopteryx Feathers and Bone Chemistry Fully Revealed via Synchrotron Imaging Archaeopteryx specimens are important but extremely rare fossils. Due to their possession of both reptilian (jaws with teeth, long bony tail) and avian (feathered wings) characters, Archaeopteryx has been crucial in the development of Darwinian evolution. Despite their importance, no Archaeopteryx specimen has ever been chemically analyzed. This in large part may be explained by the analytical obstacles

  1. Porous coatings from wire mesh for bone implants

    DOE Patents [OSTI]

    Sump, Kenneth R.

    1986-01-01

    A method of coating areas of bone implant elements and the resulting implant having a porous coating are described. Preselected surface areas are covered by a preform made from continuous woven lengths of wire. The preform is compressed and heated to assure that diffusion bonding occurs between the wire surfaces and between the surface boundaries of the implant element and the wire surfaces in contact with it. Porosity is achieved by control of the resulting voids between the bonded wire portions.

  2. ORISE: Protecting Human Subjects

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

    Protecting Human Subjects Protecting Human Subjects The U.S. Department of Energy (DOE) Human Subjects Research Program exists to ensure that all research conducted at DOE ...

  3. Human Resources Specialist (Human Resources Development)

    Broader source: Energy.gov [DOE]

    This position is located in the Leadership and Organizational Development group of Learning and Development (NHT), Human Capital Management (NH), Chief Administrative Officer (N). Human Capital...

  4. Exposure to cadmium and persistent organochlorine pollutants and its association with bone mineral density and markers of bone metabolism on postmenopausal women

    SciTech Connect (OSTI)

    Rignell-Hydbom, A.; Skerfving, S.; Lundh, T.; Lindh, C.H.; Elmstahl, S.; Bjellerup, P.; Juensson, B.A.G.; Struemberg, U.; Akesson, A.

    2009-11-15

    Environmental contaminants such as cadmium and persistent organochlorine pollutants have been proposed as risk factors of osteoporosis, and women may be at an increased risk. To assess associations between exposure to cadmium and two different POPs (2,2',4,4',5,5'-hexachlorobiphenyl CB-153, 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene p,p'-DDE), on one hand, and bone effects, on the other, in a population-based study among postmenopausal (60-70 years) Swedish women with biobanked blood samples. The study included 908 women and was designed to have a large contrast of bone mineral densities, measured with a single photon absorptiometry technique in the non-dominant forearm. Biochemical markers related to bone metabolism were analyzed in serum. Exposure assessment was based on cadmium concentrations in erythrocytes and serum concentrations of CB-153 and p,p'-DDE. Cadmium was negatively associated with bone mineral density and parathyroid hormone, positively with the marker of bone resorption. However, this association disappeared after adjustment for smoking. The major DDT metabolite (p,p'-DDE) was positively associated with bone mineral density, an association which remained after adjustment for confounders, but the effect was weak. There was no evidence that the estrogenic congener (CB-153) was associated with any of the bone markers. In conclusion, no convincing associations were observed between cadmium and POPs, on one hand, and bone metabolism markers and BMD, on the other.

  5. Use of Bone Scan During Initial Prostate Cancer Workup, Downstream Procedures, and Associated Medicare Costs

    SciTech Connect (OSTI)

    Falchook, Aaron D.; Salloum, Ramzi G.; Hendrix, Laura H.; Chen, Ronald C.

    2014-06-01

    Purpose: For patients with a high likelihood of having metastatic disease (high-risk prostate cancer), bone scan is the standard, guideline-recommended test to look for bony metastasis. We quantified the use of bone scans and downstream procedures, along with associated costs, in patients with high-risk prostate cancer, and their use in low- and intermediate-risk patients for whom these tests are not recommended. Methods and Materials: Patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database diagnosed with prostate cancer from 2004 to 2007 were included. Prostate specific antigen (PSA), Gleason score, and clinical T stage were used to define D'Amico risk categories. We report use of bone scans from the date of diagnosis to the earlier of treatment or 6 months. In patients who underwent bone scans, we report use of bone-specific x-ray, computed tomography (CT), and magnetic resonance imaging (MRI) scans, and bone biopsy within 3 months after bone scan. Costs were estimated using 2012 Medicare reimbursement rates. Results: In all, 31% and 48% of patients with apparent low- and intermediate-risk prostate cancer underwent a bone scan; of these patients, 21% underwent subsequent x-rays, 7% CT, and 3% MRI scans. Bone biopsies were uncommon. Overall, <1% of low- and intermediate-risk patients were found to have metastatic disease. The annual estimated Medicare cost for bone scans and downstream procedures was $11,300,000 for low- and intermediate-risk patients. For patients with apparent high-risk disease, only 62% received a bone scan, of whom 14% were found to have metastasis. Conclusions: There is overuse of bone scans in patients with low- and intermediate-risk prostate cancers, which is unlikely to yield clinically actionable information and results in a potential Medicare waste. However, there is underuse of bone scans in high-risk patients for whom metastasis is likely.

  6. Jefferson Lab Man Donates Bone Marrow to Save 12-Year-Old Boy | Jefferson

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

    Lab Man Donates Bone Marrow to Save 12-Year-Old Boy Jefferson Lab Man Donates Bone Marrow to Save 12-Year-Old Boy April 22, 2002 Leon Reynolds: son, husband, father, former Marine and teacher, accelerator operator and most recently, bone marrow donor. Last month, Reynolds became Jefferson Lab's first person in corporate memory to become a marrow donor. He entered the National Marrow Donor Program (NMDP) registry on Oct. 11, 2000, when the Lab sponsored a bone marrow registry drive in

  7. Bioactivation of myelotoxic xenobiotics by human neutrophil myeloperoxidase

    SciTech Connect (OSTI)

    Roy, R.R.

    1989-01-01

    Many environmental pollutants and drugs are toxic to the bone marrow. Some of these xenobiotics may initiate toxicity after undergoing bioactivation to free radicals and/or other reactive electrophiles. Peroxidases are a group of enzymes that catalyze the one-electron oxidative bioactivation of a variety of xenobiotics in vitro. Myeloperoxidase (MPO) is a peroxidative enzyme found in very high concentration in the neutrophils of human bone marrow. In this study, human MPO was evaluated to determine its ability to catalyze the in vitro bioactivation of known bone marrow toxicants that contain the aromatic hydroxyl (Ar-OH), aromatic amine (Ar-N-R{sub 2}), or heterocyclic tertiary amine ({double bond}N-R) moieties. The formation of free radical metabolites during the MPO-catalyzed bioactivation of hydroquinone and catechol (benzene metabolites), mitoxantrone and ametantrone (antitumor drugs), and chlorpromazine and promazine (antipsychotic drugs) was demonstrated by EPR spectroscopy. The reactivity of the products formed during the MPO catalyzed bioactivation of ({sup 14}C)hydroquinone and ({sup 14}C)catechol was shown by their covalent binding to protein and DNA in vitro. The covalently binding metabolite in each case is postulated to be the quinone form of the xenobiotic. In addition, both GSH and NADH were oxidized by the reactive intermediate(s) formed during the MPO-catalyzed bioactivation of many of the bone marrow toxicants tested. It was also shown that p,p-biphenol stimulated the MPO catalyzed bioactivation of both hydroquinone and catechol, while p-cresol stimulated the MPO-catalyzed bioactivation of catechol.

  8. Bone mineral density and blood metals in premenopausal women

    SciTech Connect (OSTI)

    Pollack, A.Z.; Mumford, S.L.; Wactawski-Wende, J.; Yeung, E.; Mendola, P.; Mattison, D.R.; Schisterman, E.F.

    2013-01-15

    Exposure to metals, specifically cadmium, lead, and mercury, is widespread and is associated with reduced bone mineral density (BMD) in older populations, but the associations among premenopausal women are unclear. Therefore, we evaluated the relationship between these metals in blood and BMD (whole body, total hip, lumbar spine, and non-dominant wrist) quantified by dual energy X-ray absorptiometry in 248 premenopausal women, aged 18-44. Participants were of normal body mass index (mean BMI 24.1), young (mean age 27.4), 60% were white, 20% non-Hispanic black, 15% Asian, and 6% other race group, and were from the Buffalo, New York region. The median (interquartile range) level of cadmium was 0.30 {mu}g/l (0.19-0.43), of lead was 0.86 {mu}g/dl (0.68-1.20), and of mercury was 1.10 {mu}g/l (0.58-2.00). BMD was treated both as a continuous variable in linear regression and dichotomized at the 10th percentile for logistic regression analyses. Mercury was associated with reduced odds of decreased lumbar spine BMD (0.66, 95% confidence interval: 0.44, 0.99), but overall, metals at environmentally relevant levels of exposure were not associated with reduced BMD in this population of healthy, reproductive-aged women. Further research is needed to determine if the blood levels of cadmium, lead, and mercury in this population are sufficiently low that there is no substantive impact on bone, or if effects on bone can be expected only at older ages.

  9. Patterns of Practice of Palliative Radiotherapy in Africa, Part 1: Bone and Brain Metastases

    SciTech Connect (OSTI)

    Sharma, Vinay Gaye, Papa Macoumba M.Med.; Wahab, Sherif Abdel; Ndlovu, Ntokozo; Ngoma, Twalib; Vanderpuye, Verna; Sowunmi, Anthonia; Kigula-Mugambe, Joseph; Jeremic, Branislav

    2008-03-15

    Purpose: To provide data on the pattern of practice of palliative radiotherapy (RT) on the African continent. Methods and Materials: A questionnaire was distributed to participants in a regional training course of the International Atomic Energy Agency in palliative cancer care and sent by e-mail to other institutions in Africa. Requested information included both infrastructure and human resources available and the pattern of RT practice for metastatic and locally advanced cancers. Results: Of 35 centers contacted, 24 (68%) completed the questionnaire. Although RT is used by most centers for most metastatic cancers, liver and lung metastases are treated with chemotherapy. Of 23 centers, 14 (61%) had a single RT regimen as an institutional policy for treating painful bone metastases, but only 5 centers (23%) of 23 used 8 Gy in 1 fraction. Brain metastases were being treated by RT to the whole brain to 30 Gy in 10 fractions, either exclusively (n = 13, 56%) or in addition to the use of 20 Gy in 5 fractions (n = 3, 14%). Conclusion: Radiotherapy is a major component of treatment of cancer patients in African countries. There is consensus among few centers for treatment schedules for almost all sites regarding time and dose-fractionation characteristics of RT regimens used and/or indications for the use of RT in this setting.

  10. Hypoxia induced E-cadherin involving regulators of Hippo pathway due to HIF-1α stabilization/nuclear translocation in bone metastasis from breast carcinoma

    SciTech Connect (OSTI)

    Maroni, Paola; Matteucci, Emanuela; Drago, Lorenzo; Banfi, Giuseppe; Bendinelli, Paola; Desiderio, Maria Alfonsina

    2015-01-15

    The present study deals with the molecular mechanisms involved in the regulation of E-cadherin expression under hypoxia, because the adjustment of the amount of E-cadherin due to physical stimuli of the microenvironment might influence the colonization of metastasis to skeleton. We analyzed the effect of 1% oxygen tension, that is similar to that encountered in the bone marrow by metastatic cells spreading from breast carcinoma. The purpose was to evaluate the hypoxia-orchestrated control of E-cadherin transactivation via hypoxia inducible factor-1 (HIF-1) and peroxisome proliferator activated receptor-γ (PPARγ), and the involvement of Hippo pathway members, as regulators of transcription factors. To give a translational significance to the study, we took into consideration human pair-matched ductal breast carcinoma and bone metastasis: E-cadherin and Wwox were expressed in bone metastasis but not in breast carcinoma, while HIF-1α and TAZ seemed localized principally in nuclei of metastasis and were found in all cell compartments of breast carcinoma. A close examination of the regulatory mechanisms underlying E-cadherin expression in bone metastasis was done in 1833 clone derived from MDA-MB231 cells. Hypoxia induced E-cadherin only in 1833 clone, but not in parental cells, through HIF-1 and PPARγ activities, while Wwox decreased. Since Wwox was highly expressed in bone metastasis, the effect of ectopic Wwox was evaluated, and we showed E-cadherin transactivation and enhanced invasiveness in WWOX transfected 1833 cells. Also, hypoxia was additive with ectopic Wwox remarkably enhancing HIF-1α nuclear shuttle and accumulation due to the lengthening of the half-life of HIF-1α protein; under this experimental condition HIF-1α appeared as a slower migrated band compared with control, in agreement with the phosphorylation state. The in vitro data strongly supported the almost exclusive presence of HIF-1α in nuclei of human-bone metastasis. Thus, we identified

  11. In-111 chelate conjugates of human transferrin (HTr) and mouse monoclonal anti human transferrin receptor antibody (. cap alpha. HTrR MoAb) for tumor imaging

    SciTech Connect (OSTI)

    Goodwin, D.A.; Meares, C.F.; Diamanti, C.I.; McCall, M.; McTigue, M.; Torti, F.; Martin, B.

    1984-01-01

    At least one of the major pathways of uptake of the commonly used tumor scanning agent Ga-67 is via the transferrin receptor. This suggested the use of stably radio-labeled HTr, and ..cap alpha..HTrR MoAb for tumor imaging in humans. HTr and mouse ..cap alpha..HTrR MoAb were alkylated with 1-(parabromacetamidobenzyl)-EDTA. The mM Alkylproteins, approx. =1 chelate/molecule were labeled with 1-3 mCi In-111 citrate pH/sub 5/ (Sp Act approx. = 100-300 Ci/m mole). Images were made 24 hours after 1 mCi IV and in some patients blood levels, urine excretion and digitized whole body scans were obtained at 1, 24,48 and 96 hours post injection. Ten patients with biopsy proven prostate cancer were studied with In-111 HTr, and four with In-111 ..cap alpha.. HTrR MoAb; all had positive mets on bone scan. In-111 HTr persisted in the circulation with a T1/2 of approx. = four days, approx. = 5%/day being excreted in the urine, to a total of approx. = 60% in 21 days. Nine of ten scans were false negative due to the high blood background. In-111 ..cap alpha..HTrR disappeared rapidly from the blood; with most in the bone marrow at 24 hours. ROI analysis of three patients showed whole body 94% at 24 hours, 89% at 48 hours, and 82% at 96 hours (T1/2 = 10.7 days); liver 19% at 1 hour, 25% at 24 hours, and 21% at 96 hours; spleen 3% at 1 hour, 8% at 24 hours, 7.3% at 48 hours, and 3% at 96 hours. The high bone marrow background allowed only a few of the bone mets seen as bone scan to be visualized. Other tumor types not located in bone may be more easily seen.

  12. Human-machine interactions

    DOE Patents [OSTI]

    Forsythe, J. Chris; Xavier, Patrick G.; Abbott, Robert G.; Brannon, Nathan G.; Bernard, Michael L.; Speed, Ann E.

    2009-04-28

    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.

  13. Permian Bone Spring formation: Sandstone play in the Delaware basin. Part I - slope

    SciTech Connect (OSTI)

    Montgomery, S.L.

    1997-08-01

    New exploration in the Permian (Leonardian) Bone Spring formation has indicated regional potential in several sandstone sections across portions of the northern Delaware basin. Significant production has been established in the first, second, and third Bone Spring sandstones, as well as in a new reservoir interval, the Avalon sandstone, above the first Bone Spring sandstone. These sandstones were deposited as submarine-fan systems within the northern Delaware basin during periods of lowered sea level. The Bone Spring as a whole consists of alternating carbonate and siliciclastic intervals representing the downdip equivalents to thick Abo-Yeso/Wichita-Clear Fork carbonate buildups along the Leonardian shelf margin. Hydrocarbon exploration in the Bone Spring has traditionally focused on debris-flow carbonate deposits restricted to the paleoslope. Submarine-fan systems, in contrast, extend a considerable distance basinward of these deposits and have been recently proven productive as much as 40-48 km south of the carbonate trend.

  14. ORISE: Human Subjects Protection

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

    Human Subjects Protection The Oak Ridge Institute for Science and Education (ORISE) ... U.S. Department of Energy (DOE) laboratories involved in human subjects research projects. ...

  15. Jefferson Lab Human Resources

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

    Human Resources The Human Resources team is fully integrated with Jefferson Lab's mission, committed to providing quality customer service based on expertise, innovation and ...

  16. Human Reliability Assessment

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

    ... Signup SlideShare Human Reliability Assessment HomeStationary PowerNuclear EnergyNuclear Energy Safety TechnologiesRisk and Safety AssessmentHuman Reliability Assessment ...

  17. Growth plate closure: Apex view on bone scan

    SciTech Connect (OSTI)

    Giles, P.H.; Trochei, M.; Yeates, K.

    1984-01-01

    Angular deformities of the extremities in children following premature closure of the growth plate are well known. The deformities depend on the position of an osseus bridge which forms between the epiphysis and metaphysis. Several surgical procedures including resection of the osseus bridge have been described, however, delineation of the site of fusion is difficult to define. The commonest site of growth plate arrest is the distal femoral or proximal tibial growth plate. A new technique using the bone scan has been developed which accurately defines the area and position of these osseus bridges. Two hours after injection of technetium 99m methylene diphosphonate apex views of the affected distal femoral growth plate were performed. The knee was flexed into its smallest angle. Using a pinhole collimator the gamma camera was angled to face the affected growth plate end on. The image was collected onto computer and analysed by: (I) regions of interest over segments of the growth plate to calculate the relative area of total growth plate affected: (II) generating histograms: (III) thresholding or performing isocontours to accentuate abnormal areas. The growth plate is normally uniformly increased when compared to the normal shaft of the bone. Fusion across the plate appears as an area of diminished uptake. The apex view gives a unique functional map of the growth plate such that abnormal areas are displayed, and the site, size and position of osseus fusion obtained. The technique has the potential for determining the metabolic activity of the growth plate before and after surgery. Serial studies will allow assessment of regneration of the plate and reformation of new osseus bridges.

  18. Reconstitution activity of hypoxic cultured human cord blood CD34-positive cells in NOG mice

    SciTech Connect (OSTI)

    Shima, Haruko; Takubo, Keiyo; Iwasaki, Hiroko; Yoshihara, Hiroki; Gomei, Yumiko; Hosokawa, Kentaro; Arai, Fumio; Takahashi, Takao; Suda, Toshio

    2009-01-16

    Hematopoietic stem cells (HSCs) reside in hypoxic areas of the bone marrow. However, the role of hypoxia in the maintenance of HSCs has not been fully characterized. We performed xenotransplantation of human cord blood cells cultured in hypoxic or normoxic conditions into adult NOD/SCID/IL-2R{gamma}{sup null} (NOG) mice. Hypoxic culture (1% O{sub 2}) for 6 days efficiently supported the maintenance of HSCs, although cell proliferation was suppressed compared to the normoxic culture. In contrast, hypoxia did not affect in vitro colony-forming ability. Upregulation of a cell cycle inhibitor, p21, was observed in hypoxic culture. Immunohistochemical analysis of recipient bone marrow revealed that engrafted CD34{sup +}CD38{sup -} cord blood HSCs were hypoxic. Taken together, these results demonstrate the significance of hypoxia in the maintenance of quiescent human cord blood HSCs.

  19. Stratigraphy and depositional history, Bone Spring Formation, Lea County, New Mexico

    SciTech Connect (OSTI)

    Mazzullo, L.J. )

    1987-02-01

    The Bone Spring formation of the northern Delaware basin in southeastern New Mexico produces oil in Lea County from foreshelf detrital carbonate facies, such as in Scharb field. Production there comes from several intervals. Stratigraphic correlations between the various Bone Springs units and equivalent Leonardian facies of the Northwest shelf in Lea County suggest that the Bone Spring is correlative to the Yeso Formation of the Northwest shelf. The shelf facies there are divided into lower, middle, and upper Yeso. The upper part of what has generally been considered to be Wolfcamp in some areas, beneath the lowermost Bone Spring sandstone, is inferred to be lower Leonardian (lower Yeso) throughout the area studied. A model is proposed for the sedimentologic and reservoir evolution of the Bone Spring Formation in Lea County. Permian-Pennsylvanian tectonic activity provided the initial substrate for the development of a high-energy shelf edge in early Yeso time. In early middle Yeso time, the basin filled with sediments of the 3rd and 2nd Bone Spring units, and the shelf to basin transition was more subtle. As the basin subsided with infilling, a high-energy shelf edge again developed in late middle Yeso time. With continued basin infilling by 1st Bone Springs facies, the shelf to basin transition again evolved into a more subtle feature. Continued basin subsidence caused infilling by a thick sequence of upper Yeso carbonate, which was capped by progradational shelf carbonates of the upper Yeso.

  20. Role of Nanog in the maintenance of marrow stromal stem cells during post natal bone regeneration

    SciTech Connect (OSTI)

    Bais, Manish V.; Shabin, Zabrina M.; Young, Megan; Einhorn, Thomas A.; Kotton, Darrell N.; Gerstnefeld, Louis C.

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Nanog is related to marrow stromal stem cell maintenance. Black-Right-Pointing-Pointer Increasing Nanog expression is seen during post natal surgical bone repair. Black-Right-Pointing-Pointer Nanog knockdown decreases post surgical bone regeneration. -- Abstract: Post natal bone repair elicits a regenerative mechanism that restores the injured tissue to its pre-injury cellular composition and structure and is believed to recapitulate the embryological processes of bone formation. Prior studies showed that Nanog, a central epigenetic regulator associated with the maintenance of embryonic stem cells (ESC) was transiently expressed during fracture healing, Bais et al. . In this study, we show that murine bone marrow stromal cells (MSCs) before they are induced to undergo osteogenic differentiation express {approx}50 Multiplication-Sign the background levels of Nanog seen in murine embryonic fibroblasts (MEFs) and the W20-17 murine marrow stromal cell line stably expresses Nanog at {approx}80 Multiplication-Sign the MEF levels. Nanog expression in this cell line was inhibited by BMP7 treatment and Nanog lentivrial shRNA knockdown induced the expression of the terminal osteogenic gene osteocalcin. Lentivrial shRNA knockdown or lentiviral overexpression of Nanog in bone MSCs had inverse effects on proliferation, with knockdown decreasing and overexpression increasing MSC cell proliferation. Surgical marrow ablation of mouse tibia by medullary reaming led to a {approx}3-fold increase in Nanog that preceded osteogenic differentiation during intramembranous bone formation. Lentiviral shRNA knockdown of Nanog after surgical ablation led to an initial overexpression of osteogenic gene expression with no initial effect on bone formation but during subsequent remodeling of the newly formed bone a {approx}50% decrease was seen in the expression of terminal osteogenic gene expression and a {approx}50% loss in trabecular bone mass. This

  1. Imaging regenerating bone tissue based on neural networks applied to micro-diffraction measurements

    SciTech Connect (OSTI)

    Campi, G.; Pezzotti, G.; Fratini, M.; Ricci, A.; Burghammer, M.; Cancedda, R.; Mastrogiacomo, M.; Bukreeva, I.; Cedola, A.

    2013-12-16

    We monitored bone regeneration in a tissue engineering approach. To visualize and understand the structural evolution, the samples have been measured by X-ray micro-diffraction. We find that bone tissue regeneration proceeds through a multi-step mechanism, each step providing a specific diffraction signal. The large amount of data have been classified according to their structure and associated to the process they came from combining Neural Networks algorithms with least square pattern analysis. In this way, we obtain spatial maps of the different components of the tissues visualizing the complex kinetic at the base of the bone regeneration.

  2. Recovery From Radiation-induced Bone Marrow Damage by HSP25 Through Tie2 Signaling

    SciTech Connect (OSTI)

    Lee, Hae-June; Kwon, Hee-Chung; Chung, Hee-Yong; Lee, Yoon-Jin; Lee, Yun-Sil

    2012-09-01

    Purpose: Whole-body radiation therapy can cause severe injury to the hematopoietic system, and therefore it is necessary to identify a novel strategy for overcoming this injury. Methods and Materials: Mice were irradiated with 4.5 Gy after heat shock protein 25 (HSP25) gene transfer using an adenoviral vector. Then, peripheral blood cell counts, histopathological analysis, and Western blotting on bone marrow (BM) cells were performed. The interaction of HSP25 with Tie2 was investigated with mouse OP9 and human BM-derived mesenchymal stem cells to determine the mechanism of HSP25 in the hematopoietic system. Results: HSP25 transfer increased BM regeneration and reduced apoptosis following whole-body exposure to ionizing radiation (IR). The decrease in Tie2 protein expression that followed irradiation of the BM was blocked by HSP25 transfer, and Tie2-positive cells were more abundant among the BM cells of HSP25-transferred mice, even after IR exposure. Following systemic RNA interference of Tie2 before IR, HSP25-mediated radioprotective effects were partially blocked in both mice and cell line systems. Stability of Tie2 was increased by HSP25, a response mediated by the interaction of HSP25 with Tie2. IR-induced tyrosine phosphorylation of Tie2 was augmented by HSP25 overexpression; downstream events in the Tie2 signaling pathway, including phosphorylation of AKT and EKR1/2, were also activated. Conclusions: HSP25 protects against radiation-induced BM damage by interacting with and stabilizing Tie2. This may be a novel strategy for HSP25-mediated radioprotection in BM.

  3. Proteomic profiling of bone marrow mesenchymal stem cells upon TGF-beta stimulation

    SciTech Connect (OSTI)

    Wang, Daojing; Park, Jennifer S.; Chu, Julia S.F.; Ari, Krakowski; Luo, Kunxin; Chen, David J.; Li, Song

    2004-08-08

    Bone marrow mesenchymal stem cells (MSCs) can differentiate into different types of cells, and have tremendous potential for cell therapy and tissue engineering. Transforming growth factor {beta}1 (TGF-{beta}) plays an important role in cell differentiation and vascular remodeling. We showed that TGF-{beta} induced cell morphology change and an increase in actin fibers in MSCs. To determine the global effects of TGF-{beta} on MSCs, we employed a proteomic strategy to analyze the effect of TGF-{beta} on the human MSC proteome. By using two-dimensional gel electrophoresis and electrospray ionization coupled to Quadrupole/time-of-flight tandem mass spectrometers, we have generated a proteome reference map of MSCs, and identified {approx}30 proteins with an increase or decrease in expression or phosphorylation in response to TGF-{beta}. The proteins regulated by TGF-{beta} included cytoskeletal proteins, matrix synthesis proteins, membrane proteins, metabolic enzymes, etc. TGF-{beta} increased the expression of smooth muscle (SM) {alpha}-actin and decreased the expression of gelsolin. Over-expression of gelsolin inhibited TGF-{beta}-induced assembly of SM {alpha}-actin; on the other hand, knocking down gelsolin expression enhanced the assembly of {alpha}-actin and actin filaments without significantly affecting {alpha}-actin expression. These results suggest that TGF-{beta} coordinates the increase of {alpha}-actin and the decrease of gelsolin to promote MSC differentiation. This study demonstrates that proteomic tools are valuable in studying stem cell differentiation and elucidating the underlying molecular mechanisms.

  4. Multicolor flow cytometry analysis of blood cell subsets in patients given total body irradiation before bone marrow transplantation

    SciTech Connect (OSTI)

    Clave, E.; Socie, G.; Carosella, E.

    1995-11-01

    Bone marrow transplantation has often been closely linked with accidental or intentional therapeutical irradiation. In both situations, study of the radiosensitivity of human blood cell subsets is of interest. Using one-color flow cytometry analysis of B lymphocytes, T cell subsets, and natural killer cells, we previously reported that lymphocyte subsets exhibit equal radiosensitivity. Taking advantage of recent developments in the knowledge of leukocyte differentiation antigens and flow cytometry technology we undertook a study of blood cell subsets to search for rare populations exhibiting different radiosensitivity. Thirty patients, who were delivered a 12 Gy fractionated total body irradiation as part of their conditioning regimen before transplantation for malignant disorders, were studied using multicolor flow cytometry. T and B lymphocytes showed a sharp, radiation-induced decrease, with the B lymphocytes (cluster of differentiation (CD) 19+) being the most sensitive. When analyzed by multicolor flow cytometry all major lymphocyte subsets appeared equally sensitive to the in vivo irradiation. Therefore, all major lymphocyte subsets sharing the helper phenotype (naive or memory) and the cytotoxic phenotype appeared equally sensitive to in vivo whole body irradiation. In parallel, the CD34+ cell subset remained basically unchanged after whole body irradiation. Finally, the CD3{minus}, 56+, 16+ natural killer cell subset was relatively radioresistant (91 and 74% of its initial value, after 2 and 4 Gy, respectively) as compared to other lymphocyte subsets. Our study provides evidence that T and B cell subsets seem to be highly radiosensitive in vivo. The CD34+ progenitor/stem cells and NK cells seem to be more radioresistant. This latter result might provide clues to the understanding of the pathophysiogeny of radiation-induced aplasia and of the engrafment/rejection process following bone marrow transplantation. 20 refs., 3 figs., 1 tab.

  5. Effect of a novel load-bearing trabecular Nitinol scaffold on rabbit radius bone regeneration

    SciTech Connect (OSTI)

    Gotman, Irena Gutmanas, Elazar Y.; Zaretzky, Asaph; Psakhie, Sergey G.

    2015-10-27

    The research aim was to evaluate the bone regeneration capability of novel load-bearing NiTi alloy (Nitinol) scaffolds in a critical-size defect (CSD) model. High strength “trabecular Nitinol” scaffolds were prepared by PIRAC (Powder Immersion Reaction Assisted Coating) annealing of the highly porous Ni foam in Ti powder at 900°C. This was followed by PIRAC nitriding to mitigate the release of potentially toxic Ni ions. Scaffolds phase composition and microstructure were characterized by X-ray diffraction and scanning electron microscopy (SEM/EDS), and their mechanical properties were tested in compression. New Zealand white rabbits received bone defect in right radius and were divided in four groups randomly. In the control group, nothing was placed in the defect. In other groups, NiTi scaffolds were implanted in the defect: (i) as produced, (ii) loaded with bone marrow aspirate (BMA), and (iii) biomimetically CaP-coated. The animals were sacrificed after 12 weeks. The forelimbs with scaffolds were resected, fixed, sectioned and examined in SEM. New bone formation inside the scaffold was studied by EDS analysis and by the processing of backscattered electron images. Bone ingrowth into the scaffold was observed in all implant groups, mostly next to the ulna. New bone formation was strongly enhanced by BMA loading and biomimeatic CaP coating, the bone penetrating as much as 1–1.5 mm into the scaffold. The results of this preliminary study demonstrate that the newly developed high strength trabecular Nitinol scaffolds can be successfully used for bone regeneration in critical size defects.

  6. ARM - Human Causes

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

    Study Hall About ARM Global Warming FAQ Just for Fun Meet our Friends Cool Sites Teachers Teachers' Toolbox Lesson Plans Human Causes Some of the human activities which can cause ...

  7. Human Genome: DOE Origins

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

    Human Genome Research: DOE Origins Resources with Additional Information Charles DeLisi Charles DeLisi The genesis of the Department of Energy (DOE) human genome project took place ...

  8. Fabrication of polylactide nanocomposite scaffolds for bone tissue engineering applications

    SciTech Connect (OSTI)

    Mkhabela, Vuyiswa J.; Ray, Suprakas Sinha

    2015-05-22

    Highly porous three-dimensional polylactide (PLA) scaffolds were obtained from PLA incorporated with different amounts of chitosan-modified montmorillonite (CS-MMT), through solvent casting and particulate leaching method. The processed scaffolds were tested in vitro for their possible application in bone tissue engineering. Scaffolds were characterized by Focused Ion Beam Scanning Electron Microscopy (FIB SEM), Fourier Transform Infra-Red (FTIR), and X-Ray Diffraction (XRD) to study their structure and intermolecular interactions. Bioresorbability tests in simulated body fluid (pH 7.4) were conducted to assess the response of the scaffolds in a simulated physiological condition. The FIB SEM images of the scaffolds showed a porous architecture with gradual change in morphology with increasing CS-MMT concentration. FTIR analysis revealed the presence of both PLA and CS-MMT particles on the surface of the scaffolds. XRD showed that the crystalline unit cell type was the same for all the scaffolds, and crystallinity decreased with an increase in CS-MMT concentration. The scaffolds were found to be bioresorbable, with rapid bioresorbability on the scaffolds with a high CS-MMT concentration.

  9. Porous expandable device for attachment to bone tissue

    DOE Patents [OSTI]

    Rybicki, Edmund F.; Wheeler, Kenneth Ray; Hulbert, Lewis E.; Karagianes, Manuel Tom; Hassler, Craig R.

    1977-01-01

    A device for attaching to substantially solid living bone tissue, comprising a body member having an outer surface shaped to fit approximately into an empty space in the tissue and having pores into which the tissue can grow to strengthen the bond between the device and the tissue, and adjustable means for expanding the body member against the tissue to an extent such as to provide a compressive stress capable of maintaining a snug and stable fit and of enhancing the growth of the tissue into the pores in the body member. The expanding means is adjustable to provide a stress between the tissue and the body member in the range of about 150 to 750 psi, typically 150 to 350 psi. Typically the body member comprises an expandable cylindrical portion having at least one radial slit extending longitudinally from a first end to the vicinity of the opposite (second) end thereof, at least one radial slit extending longitudinally from the second end to the vicinity of the first end thereof, and a tapered cylindrical hole extending coaxially from a wider circular opening in the first end to a narrower circular opening communicating with the second end.

  10. Dried plum diet protects from bone loss caused by ionizing radiation

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Schreurs, A. -S.; Shirazi-Fard, Y.; Shahnazari, M.; Alwood, J. S.; Truong, T. A.; Tahimic, C. G. T.; Limoli, C. L.; Turner, N. D.; Halloran, B.; Globus, R. K.

    2016-02-11

    Bone loss caused by ionizing radiation is a potential health concern for radiotherapy patients, radiation workers and astronauts. In animal studies, exposure to ionizing radiation increases oxidative damage in skeletal tissues, and results in an imbalance in bone remodeling initiated by increased bone-resorbing osteoclasts. Therefore, we evaluated various candidate interventions with antioxidant or antiinflammatory activities (antioxidant cocktail, dihydrolipoic acid, ibuprofen, dried plum) both for their ability to blunt the expression of resorption-related genes in marrow cells after irradiation with either gamma rays (photons, 2 Gy) or simulated space radiation (protons and heavy ions, 1 Gy) and to prevent bone loss.more » Dried plum was most effective in reducing the expression of genes related to bone resorption (Nfe2l2, Rankl, Mcp1, Opg, TNF-α) and also preventing later cancellous bone decrements caused by irradiation with either photons or heavy ions. Furthermore, dietary supplementation with DP may prevent the skeletal effects of radiation exposures either in space or on Earth.« less

  11. Report: EM Human Capital Initiatives

    Office of Environmental Management (EM)

    HUMAN CAPITAL September 25, 2008 Submitted by the EMAB Human Capital Subcommittee Background: The enhancement of the Office of Environmental Management's (EM) human capital has ...

  12. Skeletal remodeling dynamics: New approaches with imaging instrumentation. [Laser confocal microscopy:a2

    SciTech Connect (OSTI)

    Parks, N.J.; Pinkerton, K.E.; Seibert, J.A.; Pool, R.R.

    1991-01-01

    This report of progress and future objectives timetable is based on an included schematic of goals and objectives and the project abstract which is included as Appendix 1. Five matters are summarized in the order of (1) novel methods of calcified bone confocal microscopy and reconstruction image analysis of decalcified beagle and human cortical bone serial sections, (2) macroscopic cross-correlation of beagle and human cortical and cancellous bone fractions with CT analysis, (3) guidance to the most radiobiologically important skeletal regions of interest with the just completed {sup 90}Sr bone tumor map from life time beagle studies, (4) deposition patterns of radioactive agents that participate in apatite crystal nucleation processes in bone and leave radiation-excited electrons trapped in bone mineral, and (5) the budget period timetable. The discovery that beta particles from {sup 166}Ho (T{sub {1/2}} =26 hr, {beta}{sub max} = 1.8 MeV) phosphonic acid bone agents leave detectable, long-lived, electron paramagnetic resonance signals in bone is included in Appendix 2 as a joint report.

  13. Skeletal remodeling dynamics: New approaches with imaging instrumentation

    SciTech Connect (OSTI)

    Parks, N.J.; Pinkerton, K.E.; Seibert, J.A.; Pool, R.R.

    1991-12-01

    This report of progress and future objectives timetable is based on an included schematic of goals and objectives and the project abstract which is included as Appendix 1. Five matters are summarized in the order of (1) novel methods of calcified bone confocal microscopy and reconstruction image analysis of decalcified beagle and human cortical bone serial sections, (2) macroscopic cross-correlation of beagle and human cortical and cancellous bone fractions with CT analysis, (3) guidance to the most radiobiologically important skeletal regions of interest with the just completed {sup 90}Sr bone tumor map from life time beagle studies, (4) deposition patterns of radioactive agents that participate in apatite crystal nucleation processes in bone and leave radiation-excited electrons trapped in bone mineral, and (5) the budget period timetable. The discovery that beta particles from {sup 166}Ho (T{sub {1/2}} =26 hr, {beta}{sub max} = 1.8 MeV) phosphonic acid bone agents leave detectable, long-lived, electron paramagnetic resonance signals in bone is included in Appendix 2 as a joint report.

  14. Corporate Human Resources Information Services (CHIRS) PIA, Office of Human

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Capitol Management | Department of Energy Corporate Human Resources Information Services (CHIRS) PIA, Office of Human Capitol Management Corporate Human Resources Information Services (CHIRS) PIA, Office of Human Capitol Management Corporate Human Resources Information Services (CHIRS) PIA, Office of Human Capitol Management Corporate Human Resources Information Services (CHIRS) PIA, Office of Human Capitol Management (80.67 KB) More Documents & Publications MOX Services Unclassified

  15. Human Genome: DOE Origins

    Office of Scientific and Technical Information (OSTI)

    of the Department of Energy; DOE Technical Report; 1988 Mapping and Sequencing the Human Genome; DOE Technical Report; 1988 Understanding our Genetic Inheritance: The U.S....

  16. Jefferson Lab Human Resources

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

    ... Sponsor click on this link to nominate a student: SPONSOR NOMINATION FORM If you have any questions please contact: Human Resources Jefferson Science Associates 628 Hofstadter Rd., ...

  17. Jefferson Lab Human Resources

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

    JLab Diversity Policies 200 Human Resources 202 Equal Employment Opportunity and Affirmative Action 203 Employment 208 Employee Performance and Conduct 209 Staff Development 210 ...

  18. Jefferson Lab Human Resources

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

    Human Resources Consultants Cassandra Andrews, HR Consultant, Employee Relations & Recruitment (757) 269-7068, candrews@jlab.org Kelly Allmon, HR Consultant, Recruitment & ...

  19. Evaluation of dual energy quantitative CT for determining the spatial distributions of red marrow and bone for dosimetry in internal emitter radiation therapy

    SciTech Connect (OSTI)

    Goodsitt, Mitchell M. Shenoy, Apeksha; Howard, David; Christodoulou, Emmanuel; Dewaraja, Yuni K.; Shen, Jincheng; Schipper, Matthew J.; Wilderman, Scott; Chun, Se Young

    2014-05-15

    for external calibrations exhibited much larger RMS errors than size matched internal calibration. Use of an average body size external-to-internal calibration correction factor reduced the errors to closer to those for internal calibration. RMS errors of less than 30% or about 0.01 for the bone and 0.1 for the red marrow volume fractions would likely be satisfactory for human studies. Such accuracies were achieved for 3 × 3 segmentation of 5 mm slice images for: (a) internal calibration with 4 times dose for all size body phantoms, (b) internal calibration with 2 times dose for the small and medium size body phantoms, and (c) corrected external calibration with 4 times dose and all size body phantoms. Conclusions: Phantom studies are promising and demonstrate the potential to use dual energy quantitative CT to estimate the spatial distributions of red marrow and bone within the vertebral spongiosa.

  20. Bone morphogenetic protein-4 is overexpressed in colonic adenocarcinomas and promotes migration and invasion of HCT116 cells

    SciTech Connect (OSTI)

    Deng Haiyun; Makizumi, Ryouji; Ravikumar, T.S.; Dong Huali; Yang Wancai; Yang, W.-L. . E-mail: wlyang@nshs.edu

    2007-03-10

    Bone morphogenetic protein (BMP), a member of the TGF-{beta} superfamily, is involved in development, morphogenesis, cell proliferation and apoptosis. Dysregulation of BMP signaling has been suggested in tumorigenesis. In an analysis of human colon normal mucosa and tumors at different stages by immunohistochemistry, we observed that the intensity of BMP-4 staining in late-adenocarcinomas was stronger than that in normal mucosa and adenomas, while there was no difference in the staining of its receptors (BMPR-IA and BMPR-II) at all stages. The up-regulation of BMP-4 was further validated in another panel of tumor tissues by real-time RT-PCR, showing that BMP-4 mRNA levels in primary colonic carcinomas with liver metastasis were significantly higher than that in the matched normal mucosa. In order to understand the functional relevance of BMP-4 expression in colon cancer progression, BMP-4-overexpressing cell clones were generated from HCT116 cells. Overexpression of BMP-4 did not affect the HCT116 cell growth. The cells overexpressing BMP-4 became resistant to serum-starvation-induced apoptosis and exhibited enhanced migration and invasion characteristics. Overexpression of BMP-4 changed cell morphology to invasive spindle phenotype and induced the expression and activity of urokinase plasminogen activator (uPA). These results indicate that BMP-4 confers invasive phenotype during progression of colon cancer.

  1. Protection of Human Subjects

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2007-12-20

    The order establishes Department of Energy (DOE) procedures and responsibilities for implementing the policy and requirements set forth in 10 Code of Federal Regulations (CFR) Part 745, Protection of Human Subjects; and in DOE P 443.1A, Protection of Human Subjects, dated 12-20-07. Cancels DOE O 443.1. Canceled by DOE O 443.1B.

  2. Protection of Human Subjects

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2000-05-15

    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.

  3. The human genome project

    SciTech Connect (OSTI)

    Yager, T.D.; Zewert, T.E.; Hood, L.E. )

    1994-04-01

    The Human Genome Project (HGP) is a coordinated worldwide effort to precisely map the human genome and the genomes of selected model organisms. The first explicit proposal for this project dates from 1985 although its foundations (both conceptual and technological) can be traced back many years in genetics, molecular biology, and biotechnology. The HGP has matured rapidly and is producing results of great significance.

  4. Palliative Radiotherapy for Bone Metastases: An ASTRO Evidence-Based Guideline

    SciTech Connect (OSTI)

    Lutz, Stephen; Berk, Lawrence; Chang, Eric; Chow, Edward; Hahn, Carol; Hoskin, Peter; Howell, David; Konski, Andre; Kachnic, Lisa; Lo, Simon; Sahgal, Arjun; Silverman, Larry; Gunten, Charles von; Mendel, Ehud; Vassil, Andrew; Bruner, Deborah Watkins; Hartsell, William

    2011-03-15

    Purpose: To present guidance for patients and physicians regarding the use of radiotherapy in the treatment of bone metastases according to current published evidence and complemented by expert opinion. Methods and Materials: A systematic search of the National Library of Medicine's PubMed database between 1998 and 2009 yielded 4,287 candidate original research articles potentially applicable to radiotherapy for bone metastases. A Task Force composed of all authors synthesized the published evidence and reached a consensus regarding the recommendations contained herein. Results: The Task Force concluded that external beam radiotherapy continues to be the mainstay for the treatment of pain and/or prevention of the morbidity caused by bone metastases. Various fractionation schedules can provide significant palliation of symptoms and/or prevent the morbidity of bone metastases. The evidence for the safety and efficacy of repeat treatment to previously irradiated areas of peripheral bone metastases for pain was derived from both prospective studies and retrospective data, and it can be safe and effective. The use of stereotactic body radiotherapy holds theoretical promise in the treatment of new or recurrent spine lesions, although the Task Force recommended that its use be limited to highly selected patients and preferably within a prospective trial. Surgical decompression and postoperative radiotherapy is recommended for spinal cord compression or spinal instability in highly selected patients with sufficient performance status and life expectancy. The use of bisphosphonates, radionuclides, vertebroplasty, and kyphoplasty for the treatment or prevention of cancer-related symptoms does not obviate the need for external beam radiotherapy in appropriate patients. Conclusions: Radiotherapy is a successful and time efficient method by which to palliate pain and/or prevent the morbidity of bone metastases. This Guideline reviews the available data to define its proper use

  5. Neutron activation analysis of NBS oyster tissue (SRM 1566) and IAEA animal bone (H-5)

    SciTech Connect (OSTI)

    Lepel, E.A.; Laul, J.C.

    1984-03-01

    Instrumental and radiochemical neutron activation analysis (INAA and RNAA) were employed to measure about 37 major, minor, and trace elements in two standard reference materials: oyster tissue (SRM 1566) supplied by the National Bureau of Standards (NBS) and animal bone (H-5) supplied by the International Atomic Energy Agency (IAEA). Wherever the comparison exists, our data show excellent agreement with accepted values for each SRM. These SRM's are useful as reference standards for the analysis of biological materials. Additionally, the chondritic normalized rare earth element pattern of animal bone behaves as a smooth function of the ionic radii, as previously observed for biological materials.

  6. Human Genome Project

    SciTech Connect (OSTI)

    Block, S.; Cornwall, J.; Dally, W.; Dyson, F.; Fortson, N.; Joyce, G.; Kimble, H. J.; Lewis, N.; Max, C.; Prince, T.; Schwitters, R.; Weinberger, P.; Woodin, W. H.

    1998-01-04

    The study reviews Department of Energy supported aspects of the United States Human Genome Project, the joint National Institutes of Health/Department of Energy program to characterize all human genetic material, to discover the set of human genes, and to render them accessible for further biological study. The study concentrates on issues of technology, quality assurance/control, and informatics relevant to current effort on the genome project and needs beyond it. Recommendations are presented on areas of the genome program that are of particular interest to and supported by the Department of Energy.

  7. Dynamic T{sub 2}-mapping during magnetic resonance guided high intensity focused ultrasound ablation of bone marrow

    SciTech Connect (OSTI)

    Waspe, Adam C.; Looi, Thomas; Mougenot, Charles; Amaral, Joao; Temple, Michael; Sivaloganathan, Siv; Drake, James M.

    2012-11-28

    Focal bone tumor treatments include amputation, limb-sparing surgical excision with bone reconstruction, and high-dose external-beam radiation therapy. Magnetic resonance guided high intensity focused ultrasound (MR-HIFU) is an effective non-invasive thermotherapy for palliative management of bone metastases pain. MR thermometry (MRT) measures the proton resonance frequency shift (PRFS) of water molecules and produces accurate (<1 Degree-Sign C) and dynamic (<5s) thermal maps in soft tissues. PRFS-MRT is ineffective in fatty tissues such as yellow bone marrow and, since accurate temperature measurements are required in the bone to ensure adequate thermal dose, MR-HIFU is not indicated for primary bone tumor treatments. Magnetic relaxation times are sensitive to lipid temperature and we hypothesize that bone marrow temperature can be determined accurately by measuring changes in T{sub 2}, since T{sub 2} increases linearly in fat during heating. T{sub 2}-mapping using dual echo times during a dynamic turbo spin-echo pulse sequence enabled rapid measurement of T{sub 2}. Calibration of T{sub 2}-based thermal maps involved heating the marrow in a bovine femur and simultaneously measuring T{sub 2} and temperature with a thermocouple. A positive T{sub 2} temperature dependence in bone marrow of 20 ms/ Degree-Sign C was observed. Dynamic T{sub 2}-mapping should enable accurate temperature monitoring during MR-HIFU treatment of bone marrow and shows promise for improving the safety and reducing the invasiveness of pediatric bone tumor treatments.

  8. Protection of Human Subjects

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2007-12-20

    The Policy is to establish DOE-specific principles for the protection of human subjects involved in DOE research. Cancels DOE P 443.1. Canceled by DOE O 443.1B

  9. Protection of Human Subjects

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2000-05-15

    The purpose of this Policy is to establish DOE-specific policy for the protection of human subjects involved in DOE research. Canceled by DOE P 443.1A.

  10. Human Reliability Program Overview

    SciTech Connect (OSTI)

    Bodin, Michael

    2012-09-25

    This presentation covers the high points of the Human Reliability Program, including certification/decertification, critical positions, due process, organizational structure, program components, personnel security, an overview of the US DOE reliability program, retirees and academia, and security program integration.

  11. Human Resource Management Delegation

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    1996-06-28

    The notice is to clarifies and updates existing Human Resource Management Delegation Authorities and the levels to which they are delegated. Expired 6-28-97. Does not cancel any directives.

  12. Elemental concentrations in bones from an ancient Egyptian mummy and from a recent man

    SciTech Connect (OSTI)

    Cholewa, M.; Kwiatek, W.M.; Jones, K.W.; Schidlovsky, G.; Paschoa, A.S.; Miller, S.C.; Pecotte, J.

    1986-06-01

    Differences in elemental concentrations in bones taken from an ancient Egyptian mummy and a contemporary man were investigated by using proton induced x-ray emission (PIXE) in combination with Rutherford backscattering (RBS). Remarkable differences were noticed in the Fe/Ca and Pb/Ca relative concentrations, which were consistently higher in the contemporary man. 5 refs., 2 figs., 2 tabs.

  13. Update of the International Consensus on Palliative Radiotherapy Endpoints for Future Clinical Trials in Bone Metastases

    SciTech Connect (OSTI)

    Chow, Edward; Hoskin, Peter; Mitera, Gunita; Zeng Liang; Lutz, Stephen; Roos, Daniel; Hahn, Carol; Linden, Yvette van der; Hartsell, William; Kumar, Eshwar

    2012-04-01

    Purpose: To update the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases by surveying international experts regarding previous uncertainties within the 2002 consensus, changes that may be necessary based on practice pattern changes and research findings since that time. Methods and Materials: A two-phase survey was used to determine revisions and new additions to the 2002 consensus. A total of 49 experts from the American Society for Radiation Oncology, the European Society for Therapeutic Radiology and Oncology, the Faculty of Radiation Oncology of the Royal Australian and New Zealand College of Radiologists, and the Canadian Association of Radiation Oncology who are directly involved in the care of patients with bone metastases participated in this survey. Results: Consensus was established in areas involving response definitions, eligibility criteria for future trials, reirradiation, changes in systemic therapy, radiation techniques, parameters at follow-up, and timing of assessments. Conclusion: An outline for trials in bone metastases was updated based on survey and consensus. Investigators leading trials in bone metastases are encouraged to adopt the revised guideline to promote consistent reporting. Areas for future research were identified. It is intended for the consensus to be re-examined in the future on a regular basis.

  14. ORISE: Protecting Human Subjects Website

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

    Protecting Human Subjects Website Institutions that engage in human subjects research are required by federal policy to establish an institutional review board (IRB) to ensure that ...

  15. Human Resources | The Ames Laboratory

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

    Human Resources The mission of the Human Resource Department is to support the goals of The Ames Laboratory by providing support services which promote a work environmnent ...

  16. Human Genome Research: Decoding DNA

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

    Human Genome Research: Decoding DNA Resources with Additional Information Charles DeLisi ... role in proposing and initiating the Human Genome Program in 1986. The U.S. ...

  17. ORISE: Human Subjects Research Database

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

    Human Subjects Research Database Section 10, Part 745 of the Code of Federal Regulations ... on all research projects that involve human subjects and that are funded by DOE, ...

  18. New light on human evolution

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

    light on human evolution New light on human evolution Scientists recently unearthed 8 million-year-old gorilla fossils from the Chorora Formation in Ethiopia, which indicate the ...

  19. Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation

    SciTech Connect (OSTI)

    Chu, Tianqing; Teng, Jiajun; Jiang, Liyan; Zhong, Hua; Han, Baohui

    2014-01-17

    Highlights: DKK1 level was associated with NSCLC bone metastases. Lung tumor cells derived DKK1 inhibited osteoblast differentiation. Lung tumor cells derived DKK1 modulates ?-catenin and RUNX2. -- Abstract: Wnt/?-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferably metastasizes to skeleton. But the role of them in bone dissemination is poorly understood. This study aims to define the role of DKK1 in lung cancer bone metastases and investigate the underlying mechanism. Our results demonstrated that DKK1 over-expression was a frequent event in non-small-cell lung cancer (NSCLC) blood samples, and serous DKK1 level was much higher in bone metastatic NSCLC compared to non-bone metastatic NSCLC. We also found that conditioned medium from DKK1 over-expressing lung cancer cells inhibited the differentiation of osteoblast, determined by alkaline phosphatase activity and osteocalcin secretion, whereas the conditioned medium from DKK1 silencing lung cancer cells exhibited the opposite effects. Mechanistically, DKK1 reduced the level of ?-catenin and RUNX2, as well as inhibiting the nuclear translocation of ?-catenin. Taken together, these results suggested that lung cancer-produced DKK1 may be an important mechanistic link between NSCLC and bone metastases, and targeting DKK1 may be an effective method to treat bone metastase of NSCLC.

  20. Human Capital - DOE Directives, Delegations, and Requirements

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

    Human Capital by Website Administrator Back

  1. Human MSH2 protein

    DOE Patents [OSTI]

    Chapelle, A. de la; Vogelstein, B.; Kinzler, K.W.

    1997-01-07

    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.

  2. Human MSH2 protein

    DOE Patents [OSTI]

    de la Chapelle, Albert; Vogelstein, Bert; Kinzler, Kenneth W.

    1997-01-01

    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. The inhibitory effect of ionizing radiation on Fc and C3 receptors on mouse and human leukocytes, and the protective potential of human albumin

    SciTech Connect (OSTI)

    Herrera, M.A.; Diaz-Perches, R.; Gutierrez, M.; Gamminio, E.; Liera, C.; Nieto, P.; Weiss-Steider, B. )

    1990-08-01

    The effect that ionizing radiation has in vitro on Fc and C3 receptors was evaluated at various doses and measured by means of erythrocytes coated with antibody (EA) and erythrocytes coated with antibody and complement (EAC) rosettes on human peripheral blood leukocytes (PBL) and on mouse bone marrow cells (BMC) and PBL. We found that the number of cells with either EA and EAC rosettes decreased as the radiation doses increased, and that they were almost absent when the highest doses were employed. We obtained evidence that albumin is a natural source of radio-protection for Fc and C3 receptors, and we showed that by increasing the amount of this molecule we could completely protect receptors for EA and EAC in vitro. Finally, the possible therapeutic value of the administration of human albumin to patients undergoing radiotherapy is discussed.

  4. Human Resources | The Ames Laboratory

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

    Budget Human Resources The Human Resources function in NNSA is a vital partnership between all levels of NNSA management. It requires effective collaboration with the Service Center's Office of Human Capital Management Services. The Headquarters' Office of Human Capital Management Programs is organized into the following five divisions. Policy and Planning The Policy and Planning Division will be responsible for the development, implementation, and oversight of, human resources management

  5. Human Reliability Program Handbook

    Broader source: Energy.gov [DOE]

    The Human Reliability Program is a security and safety reliability program designed to ensure that individuals who occupy positions affording access to certain materials, nuclear explosive devices, facilities, and programs meet the highest standards of reliability and physical and mental suitability.

  6. Effect of irradiation on bone remodelling and the structural integrity of the vertebral column. Doctoral thesis

    SciTech Connect (OSTI)

    Swenson, K.N.

    1990-01-01

    The effects of therapeutic levels of radiation on the axial properties of the primate vertebral column were studied. Seven male rhesus monkeys (Macaca mulatta) were irradiated with a single does of 1300 cGy to the specific lumbar vertebrae of L2, L3, and L4. Three additional animals served as controls. Radiographs were taken before the radiation treatment and just prior to sacrifice to determine density changes in the bone. The animal subjects were sacrificed 105 days following the radiation exposure. Biomechanical testing was completed on lumbar levels 2 and 3 to identify changes in strength characteristics following radiation treatment. Histomorphometric analysis of lumbar vertebrae level 4 was completed to identify volume and surface density changes as well as cellular changes. Tetracycline, dicarbomethylaminomethyl fluorescein (DCAF), and xylenol orange were used as bone labeling agents to aid in the histomorphometry and to obtain dynamic parameter changes.

  7. Neutron activation analysis of NBS oyster tissue (SRM 1566) and IAEA animal bone (H-5)

    SciTech Connect (OSTI)

    Lepel, E.A.; Laul, J.C.

    1983-10-01

    Data have been presented for 35 elements determined by INAA for NBS oyster tissue (SRM 1566) and for 38 elements determined by INAA and RNAA for IAEA animal bone (H-5). The experimental data showed excellent agreement with published values wherever the comparison exists. Additional trace-element data in the ppb range have been presented for the elements Sc, Sb, Cs, La, Ce, Nd, Sm, Eu, Tb, Dy, Ho, Yb, Lu, Hf, Ta, W and Th in NBS oyster tissue. Also, additional trace-element data for IAEA animal bone (H-5) in the ppb range for the elements Al, Sc, Co, Rb, Cs, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Tm, Yb, lu, Hf, Ta and Th have been presented.

  8. Automatic detection of bone fragments in poultry using multi-energy x-rays

    DOE Patents [OSTI]

    Gleason, Shaun S.; Paulus, Michael J.; Mullens, James A.

    2002-04-09

    At least two linear arrays of x-ray detectors are placed below a conveyor belt in a poultry processing plant. Multiple-energy x-ray sources illuminate the poultry and are detected by the detectors. Laser profilometry is used to measure the poultry thickness as the x-ray data is acquired. The detector readout is processed in real time to detect the presence of small highly attenuating fragments in the poultry, i.e., bone, metal, and cartilage.

  9. Intra-arterial Autologous Bone Marrow Cell Transplantation in a Patient with Upper-extremity Critical Limb Ischemia

    SciTech Connect (OSTI)

    Madaric, Juraj; Klepanec, Andrej; Mistrik, Martin; Altaner, Cestmir; Vulev, Ivan

    2013-04-15

    Induction of therapeutic angiogenesis by autologous bone marrow mononuclear cell transplantation has been identified as a potential new option in patients with advanced lower-limb ischemia. There is little evidence of the benefit of intra-arterial cell application in upper-limb critical ischemia. We describe a patient with upper-extremity critical limb ischemia with digital gangrene resulting from hypothenar hammer syndrome successfully treated by intra-arterial autologous bone marrow mononuclear cell transplantation.

  10. cAMP-response-element-binding protein positively regulates breast cancer metastasis and subsequent bone destruction

    SciTech Connect (OSTI)

    Son, Jieun; Lee, Jong-Ho; Kim, Ha-Neui; Ha, Hyunil Lee, Zang Hee

    2010-07-23

    Research highlights: {yields} CREB is highly expressed in advanced breast cancer cells. {yields} Tumor-related factors such as TGF-{beta} further elevate CREB expression. {yields} CREB upregulation stimulates metastatic potential of breast cancer cells. {yields} CREB signaling is required for breast cancer-induced bone destruction. -- Abstract: cAMP-response-element-binding protein (CREB) signaling has been reported to be associated with cancer development and poor clinical outcome in various types of cancer. However, it remains to be elucidated whether CREB is involved in breast cancer development and osteotropism. Here, we found that metastatic MDA-MB-231 breast cancer cells exhibited higher CREB expression than did non-metastatic MCF-7 cells and that CREB expression was further increased by several soluble factors linked to cancer progression, such as IL-1, IGF-1, and TGF-{beta}. Using wild-type CREB and a dominant-negative form (K-CREB), we found that CREB signaling positively regulated the proliferation, migration, and invasion of MDA-MB-231 cells. In addition, K-CREB prevented MDA-MB-231 cell-induced osteolytic lesions in a mouse model of cancer metastasis. Furthermore, CREB signaling in cancer cells regulated the gene expression of PTHrP, MMPs, and OPG, which are closely involved in cancer metastasis and bone destruction. These results indicate that breast cancer cells acquire CREB overexpression during their development and that this CREB upregulation plays an important role in multiple steps of breast cancer bone metastasis.

  11. SU-E-J-250: A Methodology for Active Bone Marrow Protection for Cervical Cancer Intensity-Modulated Radiotherapy Using 18F-FLT PET/CT Image

    SciTech Connect (OSTI)

    Ma, C; Yin, Y

    2014-06-01

    Purpose: The purpose of this study was to compare a radiation therapy treatment planning that would spare active bone marrow and whole pelvic bone marrow using 18F FLT PET/CT image. Methods: We have developed an IMRT planning methodology to incorporate functional PET imaging using 18F FLT/CT scans. Plans were generated for two cervical cancer patients, where pelvicactive bone marrow region was incorporated as avoidance regions based on the range: SUV>2., another region was whole pelvic bone marrow. Dose objectives were set to reduce the volume of active bone marrow and whole bone marraw. The volumes of received 10 (V10) and 20 (V20) Gy for active bone marrow were evaluated. Results: Active bone marrow regions identified by 18F FLT with an SUV>2 represented an average of 48.0% of the total osseous pelvis for the two cases studied. Improved dose volume histograms for identified bone marrow SUV volumes and decreases in V10(average 18%), and V20(average 14%) were achieved without clinically significant changes to PTV or OAR doses. Conclusion: Incorporation of 18F FLT/CT PET in IMRT planning provides a methodology to reduce radiation dose to active bone marrow without compromising PTV or OAR dose objectives in cervical cancer.

  12. Hyaluronan in human malignancies

    SciTech Connect (OSTI)

    Sironen, R.K.; Department of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio ; Tammi, M.; Tammi, R.; Auvinen, P.K.; Anttila, M.; Department of Gynecology and Obstetrics, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio ; Kosma, V-M.

    2011-02-15

    Hyaluronan, a major macropolysaccharide in the extracellular matrix of connective tissues, is intimately involved in the biology of cancer. Hyaluronan accumulates into the stroma of various human tumors and modulates intracellular signaling pathways, cell proliferation, motility and invasive properties of malignant cells. Experimental and clinicopathological evidence highlights the importance of hyaluronan in tumor growth and metastasis. A high stromal hyaluronan content is associated with poorly differentiated tumors and aggressive clinical behavior in human adenocarcinomas. Instead, the squamous cell carcinomas and malignant melanomas tend to have a reduced hyaluronan content. In addition to the stroma-cancer cell interaction, hyaluronan can influence stromal cell recruitment, tumor angiogenesis and epithelial-mesenchymal transition. Hyaluronan receptors, hyaluronan synthases and hyaluronan degrading enzymes, hyaluronidases, are involved in the modulation of cancer progression, depending on the tumor type. Furthermore, intracellular signaling and angiogenesis are affected by the degradation products of hyaluronan. Hyaluronan has also therapeutic implications since it is involved in multidrug resistance.

  13. An Easy Tool to Predict Survival in Patients Receiving Radiation Therapy for Painful Bone Metastases

    SciTech Connect (OSTI)

    Westhoff, Paulien G.; Graeff, Alexander de; Monninkhof, Evelyn M.; Bollen, Laurens; Dijkstra, Sander P.; Steen-Banasik, Elzbieta M. van der; Vulpen, Marco van; Leer, Jan Willem H.; Marijnen, Corrie A.; Linden, Yvette M. van der

    2014-11-15

    Purpose: Patients with bone metastases have a widely varying survival. A reliable estimation of survival is needed for appropriate treatment strategies. Our goal was to assess the value of simple prognostic factors, namely, patient and tumor characteristics, Karnofsky performance status (KPS), and patient-reported scores of pain and quality of life, to predict survival in patients with painful bone metastases. Methods and Materials: In the Dutch Bone Metastasis Study, 1157 patients were treated with radiation therapy for painful bone metastases. At randomization, physicians determined the KPS; patients rated general health on a visual analogue scale (VAS-gh), valuation of life on a verbal rating scale (VRS-vl) and pain intensity. To assess the predictive value of the variables, we used multivariate Cox proportional hazard analyses and C-statistics for discriminative value. Of the final model, calibration was assessed. External validation was performed on a dataset of 934 patients who were treated with radiation therapy for vertebral metastases. Results: Patients had mainly breast (39%), prostate (23%), or lung cancer (25%). After a maximum of 142 weeks' follow-up, 74% of patients had died. The best predictive model included sex, primary tumor, visceral metastases, KPS, VAS-gh, and VRS-vl (C-statistic = 0.72, 95% CI = 0.70-0.74). A reduced model, with only KPS and primary tumor, showed comparable discriminative capacity (C-statistic = 0.71, 95% CI = 0.69-0.72). External validation showed a C-statistic of 0.72 (95% CI = 0.70-0.73). Calibration of the derivation and the validation dataset showed underestimation of survival. Conclusion: In predicting survival in patients with painful bone metastases, KPS combined with primary tumor was comparable to a more complex model. Considering the amount of variables in complex models and the additional burden on patients, the simple model is preferred for daily use. In addition, a risk table for survival is provided.

  14. Age and gender specific biokinetic model for strontium in humans

    SciTech Connect (OSTI)

    Shagina, N. B.; Tolstykh, E. I.; Degteva, M. O.; Anspaugh, L. R.; Napier, Bruce A.

    2015-03-01

    A biokinetic model for strontium in humans is necessary for quantification of internal doses due to strontium radioisotopes. The ICRP-recommended biokinetic model for strontium has limitation for use in a population study, because it is not gender specific and does not cover all age ranges. The extensive Techa River data set on 90Sr in humans (tens of thousands of measurements) is a unique source of data on long-term strontium retention for men and women of all ages at intake. These, as well as published data, were used for evaluation of age- and gender-specific parameters for a new compartment biokinetic model for strontium (Sr-AGe model). The Sr-AGe model has similar structure as the ICRP model for the alkaline earth elements. The following parameters were mainly reevaluated: gastro-intestinal absorption and parameters related to the processes of bone formation and resorption defining calcium and strontium transfers in skeletal compartments. The Sr-AGe model satisfactorily describes available data sets on strontium retention for different kinds of intake (dietary and intravenous) at different ages (080 years old) and demonstrates good agreement with data sets for different ethnic groups. The Sr-AGe model can be used for dose assessment in epidemiological studies of general population exposed to ingested strontium radioisotopes.

  15. Human Factors Engineering Analysis Tool

    Energy Science and Technology Software Center (OSTI)

    2002-03-04

    HFE-AT is a human factors engineering (HFE) software analysis tool (AT) for human-system interface design of process control systems, and is based primarily on NUREG-0700 guidance.

  16. Global Warming and Human Health

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

    American Geophysical Union Global Warming and Human Health WHEN: Jul 27, 2015 5:30 PM - ... Event Description The main reason we are concerned about human-induced climate change is ...

  17. ORISE: Protecting Human Subjects Website

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

    Protecting Human Subjects Website Institutions that engage in human subjects research are required by federal policy to establish an institutional review board (IRB) to ensure that risks to human subjects in research are minimal and to provide protection with respect to the rights and welfare of research subjects. The Oak Ridge Institute for Science and Education (ORISE) administers the Oak Ridge Sitewide Institutional Review Board (ORSIRB) and manages the ORISE Human Subjects website. The

  18. Protection of Human Research Subjects

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2011-03-17

    The Order establishes DOE-specific policy and principles for the protection of human subjects involved in DOE research, and DOE procedures and responsibilities for implementing the policy and requirements set forth in Title 45 Code of Federal Regulations (CFR) Part 46, Protection of Human Subjects, and 10 CFR Part 745, Protection of Human Subjects. Supersedes DOE O 443.1B.

  19. Human Capital Management Accountability Program

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2008-08-01

    The Order establishes requirements, roles and responsibilities for the Human Capital Management Accountability Program (HCMAP) for human resources programs and personnel and ensures that human capital activities are regulatory and procedurally compliant with Federal statutes and Departmental policies. Does not cancel other directives.

  20. Human Genome Program

    SciTech Connect (OSTI)

    Not Available

    1993-01-01

    The DOE Human Genome program has grown tremendously, as shown by the marked increase in the number of genome-funded projects since the last workshop held in 1991. The abstracts in this book describe the genome research of DOE-funded grantees and contractors and invited guests, and all projects are represented at the workshop by posters. The 3-day meeting includes plenary sessions on ethical, legal, and social issues pertaining to the availability of genetic data; sequencing techniques, informatics support; and chromosome and cDNA mapping and sequencing.

  1. Human portable preconcentrator system

    DOE Patents [OSTI]

    Linker, Kevin L.; Bouchier, Francis A.; Hannum, David W.; Rhykerd, Jr., Charles L.

    2003-01-01

    A preconcentrator system and apparatus suited to human portable use wherein sample potentially containing a target chemical substance is drawn into a chamber and through a pervious screen. The screen is adapted to capture target chemicals and then, upon heating, to release those chemicals into the chamber. Chemicals captured and then released in this fashion are then carried to a portable chemical detection device such as a portable ion mobility spectrometer. In the preferred embodiment, the means for drawing sample into the chamber comprises a reversible fan which, when operated in reverse direction, creates a backpressure that facilitates evolution of captured target chemicals into the chamber when the screen is heated.

  2. HUMAN MACHINE COOPERATIVE TELEROBOTICS

    SciTech Connect (OSTI)

    William R. Hamel; Spivey Douglass; Sewoong Kim; Pamela Murray; Yang Shou; Sriram Sridharan; Ge Zhang; Scott Thayer; Rajiv V. Dubey

    2003-06-30

    The remediation and deactivation and decommissioning (D&D) of nuclear waste storage tanks using telerobotics is one of the most challenging tasks faced in environmental cleanup. Since a number of tanks have reached the end of their design life and some of them have leaks, the unstructured, uncertain and radioactive environment makes the work inefficient and expensive. However, the execution time of teleoperation consumes ten to hundred times that of direct contact with an associated loss in quality. Thus, a considerable effort has been expended to improve the quality and efficiency of telerobotics by incorporating into teleoperation and robotic control functions such as planning, trajectory generation, vision, and 3-D modeling. One example is the Robot Task Space Analyzer (RTSA), which has been developed at the Robotics and Electromechanical Systems Laboratory (REMSL) at the University of Tennessee in support of the D&D robotic work at the Oak Ridge National Laboratory and the National Energy Technology Laboratory. This system builds 3-D models of the area of interest in task space through automatic image processing and/or human interactive manual modeling. The RTSA generates a task plan file, which describes the execution of a task including manipulator and tooling motions. The high level controller of the manipulator interprets the task plan file and executes the task automatically. Thus, if the environment is not highly unstructured, a tooling task, which interacts with environment, will be executed in the autonomous mode. Therefore, the RTSA not only increases the system efficiency, but also improves the system reliability because the operator will act as backstop for safe operation after the 3-D models and task plan files are generated. However, unstructured conditions of environment and tasks necessitate that the telerobot operates in the teleoperation mode for successful execution of task. The inefficiency in the teleoperation mode led to the research

  3. PIA - Human Resources Information System (HRIS) | Department...

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

    Information System (HRIS) PIA - Human Resources Information System (HRIS) (232.73 KB) More Documents & Publications PIA - INL PeopleSoft - Human Resource System PIA - Human ...

  4. Project ATHENA creates surrogate human organ systems

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

    Project ATHENA creates surrogate human organ systems Project ATHENA creates surrogate human organ systems The development of miniature surrogate human organs, coupled with highly ...

  5. Contractor Human Resources | National Nuclear Security Administration...

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

    Contractor Human Resources The Contractor Human Resources mission is to provide expert advice and assistance to our customers in order to ensure quality Contractor Human Resource ...

  6. New human resources division leader selected

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

    New Human Resources division leader selected New human resources division leader selected Donna J. Hampton has been named the new Human Resources Division leader. March 15, 2011 ...

  7. ORISE: Human Subjects Protection Resource Protection Book

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

    Human Subjects Protection Resource Book The Human Subjects Protection Resource Book synthesizes information currently available on the protection of human subjects in research, the ...

  8. XCR1 promotes cell growth and migration and is correlated with bone metastasis in non-small cell lung cancer

    SciTech Connect (OSTI)

    Wang, Ting; Han, Shuai; Wu, Zhipeng; Han, Zhitao; Yan, Wangjun; Liu, Tielong; Wei, Haifeng; Song, Dianwen; Zhou, Wang Yang, Xinghai Xiao, Jianru

    2015-08-21

    Bone metastasis occurs in approximately 30–40% patients with advanced non-small cell lung cancer (NSCLC), but the mechanism underlying this bone metastasis remains poorly understood. The chemokine super family is believed to play an important role in tumor metastasis in lung cancer. The chemokine receptor XCR1 has been identified to promote cell proliferation and migration in oral cancer and ovarian carcinoma, but the role of XCR1 in lung cancer has not been reported. In this study, we demonstrated for the first time that XCR1 was overexpressed in lung cancer bone metastasis as compared with that in patients with primary lung cancer. In addition, the XCR1 ligand XCL1 promoted the proliferation and migration of lung cancer cells markedly, and knockdown of XCR1 by siRNA abolished the effect of XCL1 in cell proliferation and migration. Furthermore, we identified JAK2/STAT3 as a novel downstream pathway of XCR1, while XCL1/XCR1 increased the mRNA level of the downstream of JAK2/STAT3 including PIM1, JunB, TTP, MMP2 and MMP9. These results indicate that XCR1 is a new potential therapeutic target for the treatment of lung cancer bone metastasis. - Highlights: • XCR1 is overexpressed in bone metastasis compared with primary NSCLC. • XCR1 activation by XCL1 promotes lung cancer cell proliferation and migration. • JAK2/STAT3 is a novel potential downstream pathway of XCR1.

  9. Benefit of Consolidative Radiation Therapy for Primary Bone Diffuse Large B-Cell Lymphoma

    SciTech Connect (OSTI)

    Tao, Randa; Allen, Pamela K.; Rodriguez, Alma; Shihadeh, Ferial; Pinnix, Chelsea C.; Arzu, Isadora; Reed, Valerie K.; Oki, Yasuhiro; Westin, Jason R.; Fayad, Luis E.; Medeiros, L. Jeffrey; Dabaja, Bouthaina

    2015-05-01

    Purpose: Outcomes for patients with diffuse large B-cell lymphoma (DLBCL) differ according to the site of presentation. With effective chemotherapy, the need for consolidative radiation therapy (RT) is controversial. We investigated the influence of primary bone presentation and receipt of consolidative RT on progression-free survival (PFS) and overall survival (OS) in patients with DLBCL. Methods and Materials: We identified 102 patients with primary bone DLBCL treated consecutively from 1988 through 2013 and extracted clinical, pathologic, and treatment characteristics from the medical records. Survival outcomes were calculated by the Kaplan-Meier method, with factors affecting survival determined by log-rank tests. Univariate and multivariate analyses were done with a Cox regression model. Results: The median age was 55 years (range, 16-87 years). The most common site of presentation was in the long bones. Sixty-five patients (63%) received R-CHOP–based chemotherapy, and 74 (72%) received rituximab. RT was given to 67 patients (66%), 47 with stage I to II and 20 with stage III to IV disease. The median RT dose was 44 Gy (range, 24.5-50 Gy). At a median follow-up time of 82 months, the 5-year PFS and OS rates were 80% and 82%, respectively. Receipt of RT was associated with improved 5-year PFS (88% RT vs 63% no RT, P=.0069) and OS (91% vs 68%, P=.0064). On multivariate analysis, the addition of RT significantly improved PFS (hazard ratio [HR] = 0.14, P=.014) with a trend toward an OS benefit (HR=0.30, P=.053). No significant difference in PFS or OS was found between patients treated with 30 to 35 Gy versus ≥36 Gy (P=.71 PFS and P=.31 OS). Conclusion: Patients with primary bone lymphoma treated with standard chemotherapy followed by RT can have excellent outcomes. The use of consolidative RT was associated with significant benefits in both PFS and OS.

  10. Battery of short-term tests in laboratory animals to corroborate the detection of human population exposures to genotoxic chemicals

    SciTech Connect (OSTI)

    Pereira, M.A.; Chang, L.W.; McMillan, L.; Ward, J.B.; Legator, M.S.

    1982-02-01

    The authors are conducting a battery of short-term tests in laboratory animals for comparison to a series of monitoring test they are evaluating for the detection of human population exposures to genotoxic chemicals. The human monitoring tests are described in a separate abstract. These assays include (1) hemoglobin (Hb) alkylation, (2) cytogenetic effects in bone marrow cells including chromosomal structural aberrations, sister chromatid exchange and micronucleus production, (3) DNA damage in bone marrow cells, (4) sperm morphology and (5) urine analysis for mutagens. Formaldehyde and methanol a metabolic precursor, are being evaluated in animals. The results are as follows: Hb Alkylation: the oral administration of carbon-14 radiolabeled formaldehyde or methanol to rats resulted in their covalent binding to Hb. Adducts to amino acids were separated after acid hydrolysis by an amino acid analyzer. The binding of both chemicals exhibited a linear relationship to dose between 10 and 100 umole/kg. The extent of methanol binding to Hb was greater than formaldehyde. Cytogenetic Analyses: the oral administration in mice of formaldehyde (100 mg/kg) or methanol (lg/kg) increased the incidence of chromosomal aberrations particularly aneuploidy and exchanges and the incidence of micronuclei in polychromatic erythrocytes. Results of the Hb alkylation and cytogenetic analyses will be compared to the results obtained in the human monitors studies with formaldehyde.

  11. Human subjects research handbook: Protecting human research subjects. Second edition

    SciTech Connect (OSTI)

    1996-01-30

    This handbook serves as a guide to understanding and implementing the Federal regulations and US DOE Orders established to protect human research subjects. Material in this handbook is directed towards new and continuing institutional review board (IRB) members, researchers, institutional administrators, DOE officials, and others who may be involved or interested in human subjects research. It offers comprehensive overview of the various requirements, procedures, and issues relating to human subject research today.

  12. Human Performance Modeling for Dynamic Human Reliability Analysis

    SciTech Connect (OSTI)

    Boring, Ronald Laurids; Joe, Jeffrey Clark; Mandelli, Diego

    2015-08-01

    Part of the U.S. Department of Energy’s (DOE’s) Light Water Reac- tor Sustainability (LWRS) Program, the Risk-Informed Safety Margin Charac- terization (RISMC) Pathway develops approaches to estimating and managing safety margins. RISMC simulations pair deterministic plant physics models with probabilistic risk models. As human interactions are an essential element of plant risk, it is necessary to integrate human actions into the RISMC risk framework. In this paper, we review simulation based and non simulation based human reliability analysis (HRA) methods. This paper summarizes the founda- tional information needed to develop a feasible approach to modeling human in- teractions in RISMC simulations.

  13. Human portable preconcentrator system

    SciTech Connect (OSTI)

    Linker, Kevin L.; Brusseau, Charles A.; Hannum, David W.; Puissant, James G.; Varley, Nathan R.

    2003-08-12

    A preconcentrator system and apparatus suited to human portable use wherein sample potentially containing a target chemical substance is drawn into a chamber and through a pervious screen. The screen is adapted to capture target chemicals and then, upon heating, to release those chemicals into the chamber. Chemicals captured and then released in this fashion are then carried to a portable chemical detection device such as a portable ion mobility spectrometer. In the preferred embodiment, the means for drawing sample into the chamber comprises a reversible fan which, when operated in reverse direction, creates a backpressure that facilitates evolution of captured target chemicals into the chamber when the screen is heated. The screen can be positioned directly in front of the detector prior to heating to improve detection capability.

  14. Human-computer interface

    DOE Patents [OSTI]

    Anderson, Thomas G.

    2004-12-21

    The present invention provides a method of human-computer interfacing. Force feedback allows intuitive navigation and control near a boundary between regions in a computer-represented space. For example, the method allows a user to interact with a virtual craft, then push through the windshield of the craft to interact with the virtual world surrounding the craft. As another example, the method allows a user to feel transitions between different control domains of a computer representation of a space. The method can provide for force feedback that increases as a user's locus of interaction moves near a boundary, then perceptibly changes (e.g., abruptly drops or changes direction) when the boundary is traversed.

  15. Human Reliability Program Workshop

    SciTech Connect (OSTI)

    Landers, John; Rogers, Erin; Gerke, Gretchen

    2014-05-18

    A Human Reliability Program (HRP) is designed to protect national security as well as worker and public safety by continuously evaluating the reliability of those who have access to sensitive materials, facilities, and programs. Some elements of a site HRP include systematic (1) supervisory reviews, (2) medical and psychological assessments, (3) management evaluations, (4) personnel security reviews, and (4) training of HRP staff and critical positions. Over the years of implementing an HRP, the Department of Energy (DOE) has faced various challenges and overcome obstacles. During this 4-day activity, participants will examine programs that mitigate threats to nuclear security and the insider threat to include HRP, Nuclear Security Culture (NSC) Enhancement, and Employee Assistance Programs. The focus will be to develop an understanding of the need for a systematic HRP and to discuss challenges and best practices associated with mitigating the insider threat.

  16. PIA - Human Resources - Personal Information Change Request ...

    Energy Savers [EERE]

    Human Resources - Personal Information Change Request - Idaho National Engineering Laboratory PIA - Human Resources - Personal Information Change Request - Idaho National...

  17. Careers/ Human Resources | Princeton Plasma Physics Lab

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

    Human Resources Employment Opportunities Directory Environment, Safety & Health Furth Plasma Physics Library Lab Leadership Organization Chart Technology Transfer Careers Human ...

  18. Latexin is involved in bone morphogenetic protein-2-induced chondrocyte differentiation

    SciTech Connect (OSTI)

    Kadouchi, Ichiro; Sakamoto, Kei; Tangjiao, Liu; Murakami, Takashi; Kobayashi, Eiji; Hoshino, Yuichi; Yamaguchi, Akira

    2009-01-16

    Latexin is the only known carboxypeptidase A inhibitor in mammals. We previously demonstrated that BMP-2 significantly induced latexin expression in Runx2-deficient mesenchymal cells (RD-C6 cells), during chondrocyte and osteoblast differentiation. In this study, we investigated latexin expression in the skeleton and its role in chondrocyte differentiation. Immunohistochemical studies revealed that proliferating and prehypertrophic chondrocytes expressed latexin during skeletogenesis and bone fracture repair. In the early phase of bone fracture, latexin mRNA expression was dramatically upregulated. BMP-2 upregulated the expression of the mRNAs of latexin, Col2a1, and the gene encoding aggrecan (Agc1) in a micromass culture of C3H10T1/2 cells. Overexpression of latexin additively stimulated the BMP-2-induced expression of the mRNAs of Col2a, Agc1, and Col10a1. BMP-2 treatment upregulated Sox9 expression, and Sox9 stimulated the promoter activity of latexin. These results indicate that latexin is involved in BMP-2-induced chondrocyte differentiation and plays an important role in skeletogenesis and skeletal regeneration.

  19. The content of bone morphogenetic proteins in platelets varies greatly between different platelet donors

    SciTech Connect (OSTI)

    Kalen, Anders; Wahlstroem, Ola; Linder, Cecilia Halling; Magnusson, Per

    2008-10-17

    Platelet derivates and platelet rich plasma have been used to stimulate bone formation and wound healing because of the rich content of potent growth factors. However, not all reports have been conclusive since some have not been able to demonstrate a positive effect. We investigated the interindividual variation of bone morphogenetic proteins (BMPs) in platelets from healthy donors, and the pH-dependent effect on the release of BMPs in preparations of lysed platelets in buffer (LPB). Platelet concentrates from 31 healthy donors were prepared in pH 4.3 and pH 7.4 buffers and investigated with respect to BMP-2, -4, -6, and -7. BMP-2 and BMP-4 were significantly more common in acidic LPBs in comparison with neutral preparations. We also observed a considerable variation among platelet donors with respect to the release of BMPs at pH 4.3 and 7.4. In conclusion, a considerable variation was found among platelet donors, which may be of importance considering the ambiguous results previously reported on osteoblast proliferation and differentiation.

  20. Proteasome inhibitor MG-132 lowers gastric adenocarcinoma TMK1 cell proliferation via bone morphogenetic protein signaling

    SciTech Connect (OSTI)

    Wu, William Ka Kei; Sung, Joseph Jao Yiu; Yu Le; Cho, C.H.

    2008-06-27

    Proteasome inhibitor is a novel class of cancer therapeutics, of which the mechanism of action is not fully understood. It is reported that proteasome inhibitor enhances bone morphogenetic protein (BMP) signaling in osteoblasts to stimulate bone formation. BMP signaling is also an important tumor-suppressing pathway in gastric carcinogenesis. We therefore sought to determine the anti-mitogenic effect of proteasome inhibition in relation to BMP signaling in gastric cancer cells. Results showed that proteasome inhibitor MG-132 significantly suppressed the proliferation and the colony-forming ability of gastric cancer TMK1 cells. In this connection, MG-132 activated BMP signaling, manifested as an increase in Smad1/5/8 phosphorylation and up-regulation of p21{sup Waf1/Cip1} mRNA and protein expression. Knockdown of BMP receptor II by RNA interference abolished Smad1/5/8 phosphorylation, p21{sup Waf1/Cip1} induction, and the inhibition of cell proliferation induced by MG-132. Further analysis revealed that MG-132 up-regulated the expression of BMP1 and BMP4 and suppressed the expression of Smad6. Knockdown of Smad6 also mimicked the effect of MG-132 on BMP signaling. Collectively, these findings suggest that inhibition of proteasome suppresses gastric cancer cell proliferation via activation of BMP signaling. This discovery may open up a novel therapeutic avenue to proteasome inhibitors for the management of gastric cancer.

  1. Stanford Synchrotron Radiation Lightsource

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

    ... Sheep Cortical Bone Using Synchrotron Radiation Transmission X-ray Microscopy", PLoS ONE ... Garry R. Brock, Cornell University Joy C. Andrews, Stanford Synchrotron Radiation ...

  2. ORISE: Human Subjects Research Database

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

    Human Subjects Research Database Section 10, Part 745 of the Code of Federal Regulations and U.S. Department of Energy (DOE) Orders 443.1 and 481.1 require the maintenance of information on all research projects that involve human subjects and that are funded by DOE, conducted in DOE facilities, performed by DOE personnel or involve DOE or contract personnel. The Oak Ridge Institute for Science and Education (ORISE) maintains the Human Subjects Research Database (HSRD) for the Office of

  3. Reactive oxygen species on bone mineral density and mechanics in Cu,Zn superoxide dismutase (Sod1) knockout mice

    SciTech Connect (OSTI)

    Smietana, Michael J.; Arruda, Ellen M.; Mechanical Engineering, University of Michigan, 2250 GG Brown, 2350 Hayward, Ann Arbor, MI 48109; Program in Macromolecular Science and Engineering, University of Michigan, 2250 GG Brown, 2350 Hayward, Ann Arbor, MI 48109 ; Faulkner, John A.; Brooks, Susan V.; Molecular and Integrative Physiology, University of Michigan, 2025 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200 ; Larkin, Lisa M.

    2010-12-03

    Research highlights: {yields} Reactive oxygen species (ROS) are considered to be a factor in the onset of a number of age-associated conditions, including loss of BMD. {yields} Cu,Zn-superoxide dismutase (Sod1) deficient mice have increased ROS, reduced bone mineral density, decreased bending stiffness, and decreased strength compared to WT controls. {yields} Increased ROS caused by the deficiency of Sod1, may be responsible for the changes in BMD and bone mechanics and therefore represent an appropriate model for studying mechanisms of age-associated bone loss. -- Abstract: Reactive oxygen species (ROS) play a role in a number of degenerative conditions including osteoporosis. Mice deficient in Cu,Zn-superoxide dismutase (Sod1) (Sod1{sup -/-} mice) have elevated oxidative stress and decreased muscle mass and strength compared to wild-type mice (WT) and appear to have an accelerated muscular aging phenotype. Thus, Sod1{sup -/-} mice may be a good model for evaluating the effects of free radical generation on diseases associated with aging. In this experiment, we tested the hypothesis that the structural integrity of bone as measured by bending stiffness (EI; N/mm{sup 2}) and strength (MPa) is diminished in Sod1{sup -/-} compared to WT mice. Femurs were obtained from male and female WT and Sod1{sup -/-} mice at 8 months of age and three-point bending tests were used to determine bending stiffness and strength. Bones were also analyzed for bone mineral density (BMD; mg/cc) using micro-computed tomography. Femurs were approximately equal in length across all groups, and there were no significant differences in BMD or EI with respect to gender in either genotype. Although male and female mice demonstrated similar properties within each genotype, Sod1{sup -/-} mice exhibited lower BMD and EI of femurs from both males and females compared with gender matched WT mice. Strength of femurs was also lower in Sod1{sup -/-} mice compared to WT as well as between genders. These

  4. Quantum physics and human values

    SciTech Connect (OSTI)

    Stapp, H.P.

    1989-09-01

    This report discusses the following concepts: the quantum conception of nature; the quantum conception of man; and the impact upon human values. (LSP).

  5. Human Genome Research: Decoding DNA

    Office of Scientific and Technical Information (OSTI)

    ... Speeding Up the Process of Gene Discovery Engineered Enzyme Accelerates DNA Sequencing Putting a Virus to Practical Use DOE Joint Genome Institute The Human Genome Project: ...

  6. Protection of Human Research Subjects

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2015-07-20

    Changes are made to harmonize the definitions in this Order with those in the Federal regulations for the protection of human subjects (10 CFR Part 745), specifically, splitting the definition "human subject research" into "research" and "human subject," and adopting, verbatim, the definitions of "research" and "human subject" from 10 CFR Part 745 and adding the definition of "generalizable," since the determination of whether a project is "research" in 10 CFR Part 745 hinges on whether the work being conducted is generalizable. Small corrections and updates have been made to the references, links, and organization titles.

  7. Simulating human behavior for national security human interactions.

    SciTech Connect (OSTI)

    Bernard, Michael Lewis; Hart, Dereck H.; Verzi, Stephen J.; Glickman, Matthew R.; Wolfenbarger, Paul R.; Xavier, Patrick Gordon

    2007-01-01

    This 3-year research and development effort focused on what we believe is a significant technical gap in existing modeling and simulation capabilities: the representation of plausible human cognition and behaviors within a dynamic, simulated environment. Specifically, the intent of the ''Simulating Human Behavior for National Security Human Interactions'' project was to demonstrate initial simulated human modeling capability that realistically represents intra- and inter-group interaction behaviors between simulated humans and human-controlled avatars as they respond to their environment. Significant process was made towards simulating human behaviors through the development of a framework that produces realistic characteristics and movement. The simulated humans were created from models designed to be psychologically plausible by being based on robust psychological research and theory. Progress was also made towards enhancing Sandia National Laboratories existing cognitive models to support culturally plausible behaviors that are important in representing group interactions. These models were implemented in the modular, interoperable, and commercially supported Umbra{reg_sign} simulation framework.

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

    SciTech Connect (OSTI)

    Su, Chen-Ming; Wang, Shih-Wei; Lee, Tzong-Huei; Tzeng, Wen-Pei; Hsiao, Che-Jen; Liu, Shih-Chia; Tang, Chih-Hsin

    2013-10-15

    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.

  9. The Human Genome Diversity Project

    SciTech Connect (OSTI)

    Cavalli-Sforza, L.

    1994-12-31

    The Human Genome Diversity Project (HGD Project) is an international anthropology project that seeks to study the genetic richness of the entire human species. This kind of genetic information can add a unique thread to the tapestry knowledge of humanity. Culture, environment, history, and other factors are often more important, but humanity`s genetic heritage, when analyzed with recent technology, brings another type of evidence for understanding species` past and present. The Project will deepen the understanding of this genetic richness and show both humanity`s diversity and its deep and underlying unity. The HGD Project is still largely in its planning stages, seeking the best ways to reach its goals. The continuing discussions of the Project, throughout the world, should improve the plans for the Project and their implementation. The Project is as global as humanity itself; its implementation will require the kinds of partnerships among different nations and cultures that make the involvement of UNESCO and other international organizations particularly appropriate. The author will briefly discuss the Project`s history, describe the Project, set out the core principles of the Project, and demonstrate how the Project will help combat the scourge of racism.

  10. T cells stimulate catabolic gene expression by the stromal cells from giant cell tumor of bone

    SciTech Connect (OSTI)

    Cowan, Robert W.; Juravinski Cancer Centre, 699 Concession St., Hamilton, ON, Canada L8V 5C2 ; Ghert, Michelle; Department of Surgery, McMaster University, 1280 Main St. W., Hamilton, ON, Canada L8S 4L8 ; Singh, Gurmit; Juravinski Cancer Centre, 699 Concession St., Hamilton, ON, Canada L8V 5C2

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer Two T cell lines stimulate PTHrP, RANKL, MMP13 gene expression in GCT cell cultures. Black-Right-Pointing-Pointer CD40 expressed by stromal cells; CD40L detected in whole tumor but not cultures. Black-Right-Pointing-Pointer Effect of CD40L treatment on GCT cells increased PTHrP and MMP13 gene expression. Black-Right-Pointing-Pointer PTHrP treatment increased MMP13 expression, while inhibition decreased expression. Black-Right-Pointing-Pointer T cells may stimulate GCT stromal cells and promote the osteolysis of the tumor. -- Abstract: The factors that promote the localized bone resorption by giant cell tumor of bone (GCT) are not fully understood. We investigated whether T cells could contribute to bone resorption by stimulating expression of genes for parathyroid hormone-related protein (PTHrP), matrix metalloproteinase (MMP)-13, and the receptor activator of nuclear-factor {kappa}B ligand (RANKL). Two cell lines, Jurkat clone E6-1 and D1.1, were co-cultured with isolated GCT stromal cells. Real-time PCR analyses demonstrated a significant increase of all three genes following 48 h incubation, and PTHrP and MMP-13 gene expression was also increased at 24 h. Further, we examined the expression of CD40 ligand (CD40L), a protein expressed by activated T cells, and its receptor, CD40, in GCT. Immunohistochemistry results revealed expression of the CD40 receptor in both the stromal cells and giant cells of the tumor. RNA collected from whole GCT tissues showed expression of CD40LG, which was absent in cultured stromal cells, and suggests that CD40L is expressed within GCT. Stimulation of GCT stromal cells with CD40L significantly increased expression of the PTHrP and MMP-13 genes. Moreover, we show that inhibition of PTHrP with neutralizing antibodies significantly decreased MMP13 expression by the stromal cells compared to IgG-matched controls, whereas stimulation with PTHrP (1-34) increased MMP-13 gene expression. These

  11. Wnt5a signaling is a substantial constituent in bone morphogenetic protein-2-mediated osteoblastogenesis

    SciTech Connect (OSTI)

    Nemoto, Eiji; Ebe, Yukari; Kanaya, Sousuke; Tsuchiya, Masahiro; Nakamura, Takashi; Tamura, Masato; Shimauchi, Hidetoshi

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer Wnt5a is identified in osteoblasts in tibial growth plate and bone marrow. Black-Right-Pointing-Pointer Osteoblastic differentiation is associated with increased expression of Wnt5a/Ror2. Black-Right-Pointing-Pointer Wnt5a/Ror2 signaling is important for BMP-2-mediated osteoblastic differentiation. Black-Right-Pointing-Pointer Wnt5a/Ror2 operates independently of BMP-Smad pathway. -- Abstract: Wnts are secreted glycoproteins that mediate developmental and post-developmental physiology by regulating cellular processes including proliferation, differentiation, and apoptosis through {beta}-catenin-dependent canonical and {beta}-catenin-independent noncanonical pathway. It has been reported that Wnt5a activates noncanonical Wnt signaling through receptor tyrosine kinase-like orphan receptor 2 (Ror2). Although it appears that Wnt5a/Ror2 signaling supports normal bone physiology, the biological significance of noncanonical Wnts in osteogenesis is essentially unknown. In this study, we identified expression of Wnt5a in osteoblasts in the ossification zone of the tibial growth plate as well as bone marrow of the rat tibia as assessed by immunohistochemistry. In addition, we show that osteoblastic differentiation mediated by BMP-2 is associated with increased expression of Wnt5a and Ror2 using cultured pre-osteoblasts, MC3T3-E1 cells. Silencing gene expression of Wnt5a and Ror2 in MC3T3-E1 cells results in suppression of BMP-2-mediated osteoblastic differentiation, suggesting that Wnt5a and Ror2 signaling are of substantial importance for BMP-2-mediated osteoblastic differentiation. BMP-2 stimulation induced phosphorylation of Smad1/5/8 in a similar fashion in both siWnt5a-treated cells and control cells, suggesting that Wnt5a was dispensable for the phosphorylation of Smads by BMP-2. Taken together, our results suggest that Wnt5a/Ror2 signaling appears to be involved in BMP-2-mediated osteoblast differentiation in a Smad independent

  12. Advancements in Orthopedic Intervention: Retrograde Drilling and Bone Grafting of Osteochondral Lesions of the Knee Using Magnetic Resonance Imaging Guidance

    SciTech Connect (OSTI)

    Seebauer, Christian J.; Bail, Hermann J.; Rump, Jens C. Walter, Thula Teichgraeber, Ulf K. M.

    2010-12-15

    Computer-assisted surgery is currently a novel challenge for surgeons and interventional radiologists. Magnetic resonance imaging (MRI)-guided procedures are still evolving. In this experimental study, we describe and assess an innovative passive-navigation method for MRI-guided treatment of osteochondritis dissecans of the knee. A navigation principle using a passive-navigation device was evaluated in six cadaveric knee joint specimens for potential applicability in retrograde drilling and bone grafting of osteochondral lesions using MRI guidance. Feasibility and accuracy were evaluated in an open MRI scanner (1.0 T Philips Panorama HFO MRI System). Interactive MRI navigation allowed precise drilling and bone grafting of osteochondral lesions of the knee. All lesions were hit with an accuracy of 1.86 mm in the coronal plane and 1.4 mm the sagittal plane. Targeting of all lesions was possible with a single drilling. MRI allowed excellent assessment of correct positioning of the cancellous bone cylinder during bone grafting. The navigation device and anatomic structures could be clearly identified and distinguished throughout the entire drilling procedure. MRI-assisted navigation method using a passive navigation device is feasible for the treatment of osteochondral lesions of the knee under MRI guidance and allows precise and safe drilling without exposure to ionizing radiation. This method may be a viable alternative to other navigation principles, especially for pediatric and adolescent patients. This MRI-navigated method is also potentially applicable in many other MRI-guided interventions.

  13. Human Reliability Analysis for Digital Human-Machine Interfaces

    SciTech Connect (OSTI)

    Ronald L. Boring

    2014-06-01

    This paper addresses the fact that existing human reliability analysis (HRA) methods do not provide guidance on digital human-machine interfaces (HMIs). Digital HMIs are becoming ubiquitous in nuclear power operations, whether through control room modernization or new-build control rooms. Legacy analog technologies like instrumentation and control (I&C) systems are costly to support, and vendors no longer develop or support analog technology, which is considered technologically obsolete. Yet, despite the inevitability of digital HMI, no current HRA method provides guidance on how to treat human reliability considerations for digital technologies.

  14. Bone morphogenetic protein-4 strongly potentiates growth factor-induced proliferation of mammary epithelial cells

    SciTech Connect (OSTI)

    Montesano, Roberto Sarkoezi, Rita; Schramek, Herbert

    2008-09-12

    Bone morphogenetic proteins (BMPs) are multifunctional cytokines that elicit pleiotropic effects on biological processes such as cell proliferation, cell differentiation and tissue morphogenesis. With respect to cell proliferation, BMPs can exert either mitogenic or anti-mitogenic activities, depending on the target cells and their context. Here, we report that in low-density cultures of immortalized mammary epithelial cells, BMP-4 did not stimulate cell proliferation by itself. However, when added in combination with suboptimal concentrations of fibroblast growth factor (FGF)-2, FGF-7, FGF-10, epidermal growth factor (EGF) or hepatocyte growth factor (HGF), BMP-4 potently enhanced growth factor-induced cell proliferation. These results reveal a hitherto unsuspected interplay between BMP-4 and growth factors in the regulation of mammary epithelial cell proliferation. We suggest that the ability of BMP-4 to potentiate the mitogenic activity of multiple growth factors may contribute to mammary gland ductal morphogenesis as well as to breast cancer progression.

  15. Abrogation of hybrid resistance to bone marrow engraftment by graft versus host induced immune deficiency

    SciTech Connect (OSTI)

    Hakim, F.T.; Shearer, G.M.

    1986-03-01

    Lethally irradiated F/sub 1/ mice, heterozygous at the hematopoietic histocompatibility (Hh) locus at H-2D/sup b/, reject bone marrow grafts from homozygous H-2/sup b/ parents. This hybrid resistance (HR) is reduced by prior injection of H-2/sup b/ parental spleen cells. Since injection of parental spleen cells produces a profound suppression of F/sub 1/ immune functions, the authors investigated whether parental-induced abrogation of HR was due to graft-vs-host induced immune deficiency (GVHID). HR was assessed by quantifying engraftment in irradiated mice using /sup 125/I-IUdR spleen uptake; GVHID by measuring generation of cytotoxic T lymphocytes (CTL) from unirradiated mice. They observed correlation in time course, spleen dose dependence and T cell dependence between GVHID and loss of HR. The injection of B10 recombinant congenic spleens into (B10 x B10.A) F/sub 1/ mice, prior to grafting with B10 marrow, demonstrated that only those disparities in major histocompatibility antigens which generated GVHID would result in loss of HR. Spleens from (B10 x B10.A(2R))F/sub 1/ mice (Class I disparity only) did not induce GVHID or affect HR, while (B10 x B10.A(5R)F/sub 1/ spleens (Class I and II disparity) abrogated CTL generation and HR completely. GVHID produced by a Class II only disparity, as in (B10 x B10.A(5R))F/sub 1/ spleens injected into (B6/sup bm12 x B10.A(5R))F/sub 1/ mice, was also sufficient to markedly reduce HR to B10 bone marrow. Modulation of hematopoietic graft rejection by GVHID may affect marrow engraftment in man.

  16. Radioprotective effect of combinations of WR-2721 and mercaptopropionylglycine on mouse bone marrow chromosomes

    SciTech Connect (OSTI)

    Uma Devi, P.; Prasanna, P.G. )

    1990-11-01

    The radioprotective and toxic effects of low to moderate doses of S-2-(3-aminopropylamino)ethyl phosphorothioic acid (WR-2721) and its combination with mercaptopropionylglycine (MPG) on the chromosomes of the bone marrow cells of Swiss albino mice were studied at 24 h and 14 days postirradiation. Significant protection against radiation-induced chromosome aberrations was observed with 50 mg/kg WR-2721. The protection increased with the dose of the drug administered, and the degree of protection per unit dose increment was more pronounced at lower than at higher doses. A combination of WR-2721 and MPG given before exposure resulted in a significantly greater number of normal metaphases at 24 h postirradiation compared to the respective single-drug treatment groups. On Day 14 postirradiation, when the presence of WR-2721 resulted in an increase in the frequency of aberrant cells, combination with MPG helped to reduce this value markedly, especially at WR-2721 doses below 200 mg/kg. On the basis of these results it is suggested that 150 mg/kg WR-2721 may be considered an optimum dose for combination with MPG for protection of chromosomes of bone marrow cells when repeated drug administrations are not needed. Changes in the level of glutathione (GSH) in the blood were studied at different times following the administration of 150 mg/kg WR-2721 and its combination with MPG before sham irradiation or exposure to 4.5 Gy 60Co gamma rays. The results showed that WR-2721 elevated blood GSH levels significantly above normal values by the time radiation was delivered, while MPG did not. Glutathione appears to have an important role in the action of WR-2721, while protection by MPG may not be mediated through GSH. Injection of MPG after WR-2721 helps to maintain the higher GSH level for a longer duration compared to treatment with WR-2721 alone.

  17. Likelihood of Bone Recurrence in Prior Sites of Metastasis in Patients With High-Risk Neuroblastoma

    SciTech Connect (OSTI)

    Polishchuk, Alexei L.; Li, Richard; Little, Anthony; Hawkins, Randall A.; Hamilton, Jeffrey; Lau, Michael; Tran, Hung Chi; Lemons, Richard S.; Matthay, Katherine K.; DuBois, Steven G.; and others

    2014-07-15

    Purpose/Objectives: Despite recent improvements in outcomes, 40% of children with high-risk neuroblastoma will experience relapse, facing a guarded prognosis for long-term cure. Whether recurrences are at new sites or sites of original disease may guide decision making during initial therapy. Methods and Materials: Eligible patients were retrospectively identified from institutional databases at first metastatic relapse of high-risk neuroblastoma. Included patients had disease involving metaiodobenzylguanidine (MIBG)-avid metastatic sites at diagnosis and first relapse, achieved a complete or partial response with no more than one residual MIBG-avid site before first relapse, and received no total body irradiation or therapy with {sup 131}I-MIBG before first relapse. Anatomically defined metastatic sites were tracked from diagnosis through first relapse to determine tendency of disease to recur at previously involved versus uninvolved sites and to assess whether this pattern was influenced by site irradiation. Results: Of 159 MIBG-avid metastatic sites identified among 43 patients at first relapse, 131 (82.4%) overlapped anatomically with the set of 525 sites present at diagnosis. This distribution was similar for bone sites, but patterns of relapse were more varied for the smaller subset of soft tissue metastases. Among all metastatic sites at diagnosis in our subsequently relapsed patient cohort, only 3 of 19 irradiated sites (15.8%) recurred as compared with 128 of 506 (25.3%) unirradiated sites. Conclusions: Metastatic bone relapse in neuroblastoma usually occurs at anatomic sites of previous disease. Metastatic sites identified at diagnosis that did not receive radiation during frontline therapy appeared to have a higher risk of involvement at first relapse relative to previously irradiated metastatic sites. These observations support the current paradigm of irradiating metastases that persist after induction chemotherapy in high-risk patients. Furthermore

  18. Percutaneous Bone Biopsies: Comparison between Flat-Panel Cone-Beam CT and CT-Scan Guidance

    SciTech Connect (OSTI)

    Tselikas, Lambros Joskin, Julien; Roquet, Florian; Farouil, Geoffroy; Dreuil, Serge; Hakimé, Antoine Teriitehau, Christophe; Auperin, Anne; Baere, Thierry de Deschamps, Frederic

    2015-02-15

    PurposeThis study was designed to compare the accuracy of targeting and the radiation dose of bone biopsies performed either under fluoroscopic guidance using a cone-beam CT with real-time 3D image fusion software (FP-CBCT-guidance) or under conventional computed tomography guidance (CT-guidance).MethodsSixty-eight consecutive patients with a bone lesion were prospectively included. The bone biopsies were scheduled under FP-CBCT-guidance or under CT-guidance according to operating room availability. Thirty-four patients underwent a bone biopsy under FP-CBCT and 34 under CT-guidance. We prospectively compared the two guidance modalities for their technical success, accuracy, puncture time, and pathological success rate. Patient and physician radiation doses also were compared.ResultsAll biopsies were technically successful, with both guidance modalities. Accuracy was significantly better using FP-CBCT-guidance (3 and 5 mm respectively: p = 0.003). There was no significant difference in puncture time (32 and 31 min respectively, p = 0.51) nor in pathological results (88 and 88 % of pathological success respectively, p = 1). Patient radiation doses were significantly lower with FP-CBCT (45 vs. 136 mSv, p < 0.0001). The percentage of operators who received a dose higher than 0.001 mSv (dosimeter detection dose threshold) was lower with FP-CBCT than CT-guidance (27 vs. 59 %, p = 0.01).ConclusionsFP-CBCT-guidance for bone biopsy is accurate and reduces patient and operator radiation doses compared with CT-guidance.

  19. Human Genome Education Program

    SciTech Connect (OSTI)

    Richard Myers; Lane Conn

    2000-05-01

    The funds from the DOE Human Genome Program, for the project period 2/1/96 through 1/31/98, have provided major support for the curriculum development and field testing efforts for two high school level instructional units: Unit 1, ''Exploring Genetic Conditions: Genes, Culture and Choices''; and Unit 2, ''DNA Snapshots: Peaking at Your DNA''. In the original proposal, they requested DOE support for the partial salary and benefits of a Field Test Coordinator position to: (1) complete the field testing and revision of two high school curriculum units, and (2) initiate the education of teachers using these units. During the project period of this two-year DOE grant, a part-time Field-Test Coordinator was hired (Ms. Geraldine Horsma) and significant progress has been made in both of the original proposal objectives. Field testing for Unit 1 has occurred in over 12 schools (local and non-local sites with diverse student populations). Field testing for Unit 2 has occurred in over 15 schools (local and non-local sites) and will continue in 12-15 schools during the 96-97 school year. For both curricula, field-test sites and site teachers were selected for their interest in genetics education and in hands-on science education. Many of the site teachers had no previous experience with HGEP or the unit under development. Both of these first-year biology curriculum units, which contain genetics, biotechnology, societal, ethical and cultural issues related to HGP, are being implemented in many local and non-local schools (SF Bay Area, Southern California, Nebraska, Hawaii, and Texas) and in programs for teachers. These units will reach over 10,000 students in the SF Bay Area and continues to receive support from local corporate and private philanthropic organizations. Although HGEP unit development is nearing completion for both units, data is still being gathered and analyzed on unit effectiveness and student learning. The final field testing result from this analysis will

  20. Human genome. 1993 Program report

    SciTech Connect (OSTI)

    Not Available

    1994-03-01

    The purpose of this report is to update the Human Genome 1991-92 Program Report and provide new information on the DOE genome program to researchers, program managers, other government agencies, and the interested public. This FY 1993 supplement includes abstracts of 60 new or renewed projects and listings of 112 continuing and 28 completed projects. These two reports, taken together, present the most complete published view of the DOE Human Genome Program through FY 1993. Research is progressing rapidly toward 15-year goals of mapping and sequencing the DNA of each of the 24 different human chromosomes.

  1. Contractor Human Resource Management Programs

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    1996-09-30

    The purpose of this directive is to establish Department of Energy (DOE) responsibilities and requirements for the management and oversight of contractor Human Resource Management (HR) programs. Chg 1, 5-8-98; Chg 2, 11-22-09.

  2. Contractor Human Resource Management Programs

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    1996-09-30

    The purpose of this directive is to establish Department of Energy (DOE) responsibilities and requirements for the management and oversight of contractor Human Resource Management (HR) programs. Chg 1, 5-8-98; Chg 2, 11-22-09

  3. Protection of Human Research Subjects

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2009-12-09

    The order establishes Department of Energy (DOE) procedures and responsibilities for implementing the policy and requirements set forth in Title 10 Code of Federal Regulations (CFR) Part 745, Protection of Human Subjects, 45 CFR Part 46, and the Secretarial Policy Memorandum on Military or Intelligence-Related Human Subject Research, December 9, 2009. Supersedes DOE O 443.1A and DOE P 443.1A.

  4. Rocky Mountain Humane Investing | Open Energy Information

    Open Energy Info (EERE)

    Rocky Mountain Humane Investing Jump to: navigation, search Name: Rocky Mountain Humane Investing Place: Allenspark, Colorado Zip: 80510 Product: Allenspark-based investment...

  5. Climate Human Capital | Open Energy Information

    Open Energy Info (EERE)

    Human Capital Jump to: navigation, search Name: Climate Human Capital Place: London, United Kingdom Zip: W1K 6NG Sector: Carbon, Renewable Energy, Services Product: Green executive...

  6. Solar Energy Education. Humanities: activities and teacher's...

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

    Humanities: activities and teacher's guide. Field test edition Citation Details In-Document Search Title: Solar Energy Education. Humanities: activities and teacher's guide. Field ...

  7. Habitat for Humanity | Open Energy Information

    Open Energy Info (EERE)

    Habitat for Humanity Jump to: navigation, search Name: Habitat for Humanity Place: Americus, GA Website: www.habitat.org References: NREL Technical Report: Zero Energy Home1...

  8. Human Reliability Program Orientation for Employees (Technical...

    Office of Scientific and Technical Information (OSTI)

    Human Reliability Program Orientation for Employees Citation Details In-Document Search ... PERSONNEL; RELIABILITY; US DOE HRP employee orientation, human reliability Word ...

  9. Human Capital Management | Department of Energy

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

    human capital requires comprehensive planning and analysis in order to develop, implement, and evaluate programs that support every facet of employee work life. DOE human capital ...

  10. Human Capital Management Accountability Program (HCMAP) | Department...

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

    Human Capital Management Accountability Program (HCMAP) is an online program which serves ... and financial HR metrics that assist human resources professionals in identifying ...