Increasing evidence suggests that the deleterious effects of alcohol abuse are related to changes at the cellular level. We, therefore, have assembled a group of biochemists, biophysicists and pathologists to explore the central theme of """"""""Alcohol and the Cell"""""""". We propose to study the alterations in structure and function produced by ethanol and/or acetaldehyde in vitro, and of chronic ethanol feeding, in cells from various organs and subcellular constitutents, e.g., membranes, mitochondria, sarcoplasmic and endoplasmic reticulum, synaptosomes, etc., using the techniques of biophysics, biochemistry and quantitative histochemistry. Such techniques include fluorescence polarization, fluorescence lifetime measurements, electron paramagnetic resonance, nuclear magnetic resonance, X-ray and neutron diffraction, particle electrophoresis and electron microscopic immunocytochemistry. We intend to study the physical properties of membranes, alcohol-dependent necrosis, mitochondrial membrane assembly and the response to hormones in the liver and other tissues. Metabolic studies will include 31P NMR investigations of changes in nucleotide and metabolite levels in isolated cells and perfused organs, quantitative histochemistry of individual cells localized in the lobules of the liver and studies of collagen production by individual cells, using electron microscopic immune histochemistry. It is likely that the initial effects of ethanol are similar in all cells, and that the patterns of injury and adaptation reflect cellular specialization. It is therefore reasonable to hope that the elucidation of alterations at the cellular level will provide a key to the understanding of various ethanol-related diseases.
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