Date of Award


Document Type

Dissertation - Restricted

Degree Name

Doctor of Philosophy (PhD)



First Advisor

James J. Smith

Second Advisor

John P. Kampine

Third Advisor

Howard M. Klitgaard

Fourth Advisor

William J. Stekiel

Fifth Advisor

Robert W. Rasch


The interfacing of basic science and clinical medicine is occurring along an ever broadening front and at an unprecedented rate. Nowhere is this more apparent than in the clinical chemistry laboratory. And of the diagnostic arsenal available to the clinician, one of the most widely used and useful is clinical enzymology. Through the measurement of vast numbers of enzymes and isoenzymes, in blood and various other body fluids, a relatively non-invasive method exists for making organ specific diagnosis of various pathologic processes including infarction, inflammation, and tumor invasion as examples. Yet despite the rapid advances in the clinical application of diagnostic enzymology, little is known about the basic mechanisms responsible for the enzyme perturbations measured. Knowledge of these mechanisms is necessary and serves as a
model for the merging of basic science and medicine. Study of the problem requires investigation of fundamental cell physiology and pathologic alterations of the physiologic processes, while the data generated provides answers to existing clinical situations and opens new avenue for clinical application of enzyme interpretation. This dissertation investigated the possibility that loss of lysosomal integrity may be the inciting event for release of enzymes from cells. While other deranged cellular events may also participate in the process, it was anticipated that the results obtained would provide an initial unifying concept concerning the mechanism responsible for enzyme release.



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