The morphology core unit will serve to: a. Provide information by light and electron microscopy on the specific cellular targets of injury in the various protocols in this proposal and define the features of these lesions. Such information is an essential prerequisite for understanding the mechanisms of such injury. b. Provide quantitative data by morphometric techniques on the extent of the various lesions for possible correlation with functional abnormalities. c. Make available special techniques such as immunohistochemistry and autoradiography for probing the mechanisms of functional abnormalities. d. Examine specifically the nature of the pathologic changes in oxidant and elastase mediated injury in the lung and kidney. Our previous studies in a kidney model have shown that oxidant injury in proximal tubule cells has distinctive pathologic features which include prominent cytoplasmic vacuoles and plasma membrane disruption along with a remarkable maintenance of integrity of mitochondria. We have also shown that blood vessels may be a major target of oxidant injury importantly contributing to the associated renal dysfunction. The goal of the present studies will be to further define the nature of oxidant injury in the kidney and extend our observations to the lung. The unit will be directed by Paul F. Shanley, M.D., and attending pathologist and director of Electron Microscopy in the Department of Pathology at the University of Colorado Health Sciences Center. All preparation and analysis will be done with personnel, equipment and methodology currently operational in the Department of Pathology. The methods available include light microscopy with routine paraffin embedding, light microscopy on large plastic embedded one micron sections, transmission electron microscopy, morphometry with a computer assisted image analyzer, immunostaining by peroxidase methods and autoradiography.
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