Oculocutaneous and ocular pigment defects in man and selected animal models are investigated for their clinical, ophthalmologic, hematologic, otic, biochemical, ultrastructural, genetic, epidemiologic and pleiotropic features to determine the biochemical or dysmorphic basic of these disorders with the objective of improving diagnostic, therapeutic, and counseling means of preventing, ameliorating or treating these disorders. Investigation of unusual kindreds and matings in man are utilized to determine genetic loci, their allelism and linkage relationship and the effect of these genes on morphology and chemistry of pigmentogenesis. Morphologic and chemical methods are used to define specific steps in pigment formation and to determine those defective in hypopigmented disorders and to determine methods of circumventing these blocks. The associated defects in platelets and leukocyte function and storage disease are investigated in Hermansky-Pudlak, Chediak-Higashi and other disorders. The role of melanin in the inner ear in noise trauma, ototoxic drugs and neuronal routing is investigated in animals and man. The effects of treatment of vitiligo by PUVA and prostaglandin inhibitors and the role of prostaglandins in this condition is evaluated. Methods used will analyze all components of the pigment pathway, including: 1) tyrosinase activity and kinetic properties at the tyrosine, dopa and 5,6-dihydroxyindole step; 2) tyrosinase turnover; 3) tyrosinase elelctrophoretic pattern, 4) tyrosine uptake, 5) tyrosine and pathway intermediate compound levels in plasma and urine; 6) glutathione levels in hairbulbs; 7) dopachrome oxidoreductase activity; 8) melanin analysis by electrophoresis, ESR, and chemical assay; 9) hairbulb morphology by EM; and 10) hairshaft morphology after clearing.
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