This PPG is concerned with increasing knowledge of the biophysics and molecular biology of urolithiasis. Project 1 deals with physical chemical problems relevant to urolithiasis, primarily of calcium oxalate and especially its surface chemistry. Also, an oxalate carboylase to be used to develop an antistone therapy will be characterized in detail. Project 2 will develop an improved understanding of the cause of idiopathic renal calculi by determining the composition of the major urinary inhibitor of calcium availability for crystal formation. Project 3 will investigate specific processes which form a scenario of the detailed mechanism of urolithiasis. Studied will be the roles played by (1) degradation products from cellular injury, (2) phospholipids from urine and from stone matrix and (3) renal tubular injury products that interfere with crystallization inhibitory activity. Project 4 will continue efforts to prevent calcium oxalate encrustation on medical devices used in the urinary tract and explore the development of an implantable immobilized oxidase system for lowering system oxalate and reducing stone-forming potential. Project 5 will explore an antistone therapy through development of a method for expression in a mammalian system of an oxylase gene from Oxalabacter formigenes via the hematopoietic system. Project 6 will characterize and model the fracture of urinary stones by extracorporeal shockwave lithotripsy in order to determine the most important parameters affecting the fracture process. Core A will provide a quantitative analysis service for a wide range of chemical substances found in urines generated by Projects 1,2,3,4 and 5. Core B will provide particle characterization services to Projects 1,3 and 6. Computer services including data reduction, analysis, computer graphics and software development will be provided to all projects as required. Development and use of models of particle production, evolution and transport in the renal system will be continued. Core C will provide budget administration for the entire program project, coordinate activities among projects and between projects and the host institution and other required administrative and secretarial services.
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