This Program Project Grant consists of 4 projects and 3 cores designed to optimize the utility of nuclear magnetic resonance spectroscopy in both basic research and clinical research. Three of the projects concentrate on studying specific metabolic pathways in well-controlled pathological states. One of these investigates the metabolism of isolated, arterially perfused hepatomas of varying degrees of malignancy. Another seeks to determine the metabolic causes for the elevated phospholipid metabolites observed in virtually all tumors and transformed cell lines. The third project proposes to develop and apply methodology with the highest possible sensitivity to acquire and display metabolic information in well localized 31P and 1H spectra from humans. The remaining project will measure changes in metabolite levels and energy metabolism in human muscle and brain brought about by cancer-induced cachexia and how these changes respond to parenteral therapy. The Chemistry Core provides synthetic organic chemistry support to the projects as well as extending their analytical procedures for extracts and developing non-NMR related techniques to enhance detection sensitivity. The Instrument and Computer Core provides both the technical support necessary to develop special purpose NMR coils and probes required in the projects, as well as essential computer support for the analysis and display of the complex datasets arising from the localized spectroscopy. An Administrative Core provides budgetary control and clerical services for the PPG.
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