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Biomedical subjects

Jason D White

Publications and source records attributed to Jason D White.

8 recordsLinked to original sources

Vibrationally promoted electron emission from low work-function metal surfaces.

We observe electron emission when vibrationally excited NO molecules with vibrational state v, in the range of 9 < or = v < or =18, are scattered from a Cs-dosed Au surface. The quantum efficiency increases strongly with v, increasing up to 10(-2) electrons per NO (v) collision, a value several orders of magnitude larger than that observed in experiments with similar molecules in the ground vibrational state. The electron emission signal, as a function of v, has a threshold where the vibrational excitation energy slightly exceeds the surface work function. This threshold behavior strongly suggests that we are observing the direct conversion of NO vibrational energy into electron kinetic energy. Several potential mechanisms for the observed electron emission are explored, including (1) vibrational autodetachment, (2) an Auger-type two-electron process, and (3) vibrationally promoted dissociation. The results of this work provide direct evidence for nonadiabatic energy-transfer events associated with large amplitude vibrational motion at metal surfaces.

Journal Article↗

Evidence for environmental contamination in residential neighborhoods surrounding the defense depot of Memphis, Tennessee.

An interdisciplinary environmental assessment team from the Howard University Environmental Justice Partnership (HUEJP) conducted a site visit and assessment of the Defense Depot of Memphis, Tennessee in February of 2000. This depot was built in the late 1940's for storage of numerous chemicals and munitions. As the years progressed, many Memphis citizens have grown to believe that the activities and chemical stockpile located at this site have negatively affected the health environment of their residents. There is anecdotal evidence and documentation of numerous cancers and other illnesses in those local territories, and specifically, at the Memphis Depot site. Currently, this depot is closed and in remediation by the local government. Particularly, citizens of the Rozelle community have started a campaign to investigate any signs of exposure pathways to noted health risks. The HUEJP was contacted and asked to investigate the community concerns. Obliging to the request, we aimed to sample at three drainage sites and a residential site, talk to local citizens, and gain any additional information that would be helpful in relieving anxiety in the Rozelle community. Soil, sediment, and water samples were collected and analyzed for total organic carbon, inorganic anions, and heavy metals. These data show that for the four sites sampled, the highest concentrations of organic compounds and heavy metals were located either within a residential area or in an area with a direct transport pathway to the community. Atomic absorption analysis revealed detectable amounts of cadmium, lead and chromium metals at all sites with direct transport pathways into the residential community, with chromium concentrations being far in excess of the EPA standard limits.

Environmental Pollutants↗

Conversion of large-amplitude vibration to electron excitation at a metal surface.

Gaining insight into the nature and dynamics of the transition state is the essence of mechanistic investigations of chemical reactions, yet the fleeting configuration when existing chemical bonds dissociate while new ones form is extremely difficult to examine directly. Adiabatic potential-energy surfaces--usually derived using quantum chemical methods that assume mutually independent nuclear and electronic motion--quantify the fundamental forces between atoms involved in reaction and thus provide accurate descriptions of a reacting system as it moves through its transition state. This approach, widely tested for gas-phase reactions, is now also commonly applied to chemical reactions at metal surfaces. There is, however, some evidence calling into question the correctness of this theoretical approach for surface reactions: electronic excitation upon highly exothermic chemisorption has been observed, and indirect evidence suggests that large-amplitude vibrations of reactant molecules can excite electrons at metal surfaces. Here we report the detection of 'hot' electrons leaving a metal surface as vibrationally highly excited NO molecules collide with it. Electron emission only occurs once the vibrational energy exceeds the surface work function, and is at least 10,000 times more efficient than the emissions seen in similar systems where large-amplitude vibrations were not involved. These observations unambiguously demonstrate the direct conversion of vibrational to electronic excitation, thus questioning one of the basic assumptions currently used in theoretical approaches to describing bond-dissociation at metal surfaces.

Journal Article↗

Insulin-like growth factor I slows the rate of denervation induced skeletal muscle atrophy.

Loss of the nerve supply to skeletal muscle results in a relentless loss of muscle mass (atrophy) over time. The ability of insulin-like growth factor-1 to reduce atrophy resulting from denervation was examined after transection of the sciatic nerve in transgenic MLC/mIGF-1 mice that over-express mIGF-1 specifically in differentiated myofibres. The cross sectional area (CSA) of all types of myofibres and specifically type IIB myofibres was measured in tibialis anterior muscles from transgenic and wild-type mice at 28 days after denervation. There was a marked myofibre atrophy ( approximately 60%) in the muscles of wild-type mice over this time with increased numbers of myofibres with small CSA. In the muscles of MLC/mIGF-1 mice, over-expression of mIGF-1 reduced the rate of denervation induced myofibre atrophy by approximately 30% and preserved myofibres with larger CSA, compared to wild-type muscles. It is proposed that the protective effect of mIGF-1 on denervated myofibres might be due to reduced protein breakdown.

Animals↗

Early regeneration of whole skeletal muscle grafts is unaffected by overexpression of IGF-1 in MLC/mIGF-1 transgenic mice.

Early myogenic events in regenerating whole muscle grafts were compared between transgenic MLC/mIGF-1 mice with skeletal muscle-specific overexpression of the Exon-1 Ea isoform of insulin-like growth factor-1 (mIGF-1) and control FVB mice, from day 3 to day 21 after transplantation. Immunocytochemistry with antibodies against desmin showed that skeletal muscle-specific overexpression of IGF-1 did not affect the pattern of myoblast activation or proliferation or the onset and number of myotubes formed in regenerating whole muscle grafts. Hypertrophied myotubes were observed in MLC/mIGF grafts at day 7 after transplantation, although such hypertrophy was transient, and the transgenic and control grafts had a similar appearance at later time points (days 10, 14, and 21). Immunostaining with antibodies to platelet endothelial cell adhesion molecule-1, which identifies endothelial cells, demonstrated no difference in the formation of new vascular network in grafts of transgenic and control mice. Skeletal muscle-specific overexpression of mIGF-1 does not appear to stimulate the early events associated with myogenesis during regeneration of whole muscle grafts.

Animals↗

An evaluation of leukaemia inhibitory factor as a potential therapeutic agent in the treatment of muscle disease.

The exogenous delivery of growth factors and cytokines is a potential therapeutic strategy to alleviate the degenerative effects of primary inherited myopathies such as Duchenne muscular dystrophy. The mdx mouse diaphragm is a model for examining the progressive degeneration of dystrophic muscle. We have delivered leukaemia inhibitory factor to the mdx diaphragm using slow release alginate gels. Previous studies have reported an improvement in the histology of mdx diaphragms after delivery of leukaemia inhibitory factor in a similar manner, but little attention has been paid to the mechanism by which leukaemia inhibitory factor acts. We have used autoradiography to examine cell proliferation, Evans Blue Dye to examine myofibre damage, and morphometric analysis to examine histology in leukaemia-inhibitory-factor-treated diaphragms and compared them with untreated mdx and normal C57Bl10/ScSn diaphragms. Autoradiography showed that although myoblast proliferation was significantly increased in leukaemia inhibitory factor-treated mdx diaphragms, leukaemia inhibitory factor did not reduce myofibre damage and no histological improvement was observed. The data presented here, while demonstrating a role for leukaemia inhibitory factor in myoblast proliferation, do not support a strong and consistent benefit of leukaemia inhibitory factor on dystrophic muscle in vivo as a means of alleviating the effects of chronic dystrophic muscle degeneration.

Animals↗

The role of stem cells in skeletal and cardiac muscle repair.

In postnatal muscle, skeletal muscle precursors (myoblasts) can be derived from satellite cells (reserve cells located on the surface of mature myofibers) or from cells lying beyond the myofiber, e.g., interstitial connective tissue or bone marrow. Both of these classes of cells may have stem cell properties. In addition, the heretical idea that post-mitotic myonuclei lying within mature myofibers might be able to re-form myoblasts or stem cells is examined and related to recent observations for similar post-mitotic cardiomyocytes. In adult hearts (which previously were not considered capable of repair), the role of replicating endogenous cardiomyocytes and the recruitment of other (stem) cells into cardiomyocytes for new cardiac muscle formation has recently attracted much attention. The relative contribution of these various sources of precursor cells in postnatal muscles and the factors that may enhance stem cell participation in the formation of new skeletal and cardiac muscle in vivo are the focus of this review. We concluded that, although many endogenous cell types can be converted to skeletal muscle, the contribution of non-myogenic cells to the formation of new postnatal skeletal muscle in vivo appears to be negligible. Whether the recruitment of such cells to the myogenic lineage can be significantly enhanced by specific inducers and the appropriate microenvironment is a current topic of intense interest. However, dermal fibroblasts appear promising as a realistic alternative source of exogenous myoblasts for transplantation purposes. For heart muscle, experiments showing the participation of bone marrow-derived stem cells and endothelial cells in the repair of damaged cardiac muscle are encouraging.

Animals↗

The role of p53 in vivo during skeletal muscle post-natal development and regeneration: studies in p53 knockout mice.

The tumour suppressor gene p53 is recognised as a central regulator of the cell cycle and apoptosis. Post-natally, p53 mutations are associated with many cancers and mice lacking p53 are prone to spontaneous tumour formation. The present study examines skeletal muscle formation in post-natal mice lacking p53 using two different models of skeletal muscle regeneration. The level of endogenous myogenic cell proliferation in mature skeletal muscle was examined and the time course of muscle regeneration after whole muscle transplantation or crush injury were compared in p53 (-/-) and control C57Bl/6J adult mice, using desmin and proliferating cell nuclear antigen (PCNA) immunohistochemistry and histological analysis. The pattern of inflammation, myoblast proliferation and myotube formation in regenerating p53 (-/-) skeletal muscles appears normal and similar to those in control C57Bl/6J muscle. These data indicate that p53 is not required for the regulation of myoblast proliferation, differentiation and myotube formation in vivo during myogenesis of adult skeletal muscle.

Animals↗