EXCEED THE SPACE PROVIDED.The overall goal of the General Clinical Research Center (GCRC) at Dallas is to provide an optimalenvironment for patient-oriented investigation which leads to an improved understanding of thedisease process, allows better methods of diagnosis and treatment, fosters interdisciplinarycollaboration, and offers training in clinical investigation. Major patient-oriented research activitiesof the GCRC include: to characterize the phenotype and metabolic abnormalities, and elucidationof genetic defects in patients with congenital generalized and familial partial iipodystrophies; tostudy pathophysiology of absorptive hypercalciuria, including the clinical significance of recentlydiscovered absorptive hypercalciuria-related adenyl cyclase (AHRAC) gene, effect of dietaryanimal protein excess in causing hypercalciuria and to elucidate dietary calcium-oxalateinteraction; to study influence of recently discovered polymorphisms in the genes affecting steroltransport (ABCG5 and ABCG8) on plasma low density lipoprotein cholesterol levels, sterolconcentrations and ratios, and body pools of sterols; to study the pathophysiology, particularlyrelated to insulin resistance in gouty diathesis (renal stone formation associated with gout), andthe effects of improving insulin sensitivity in reversing the biochemical defects; to determine thesignificance of Tyr594Met polymorphism in epithelial channel locus (ENaC) in patients withessential hypertension and to study blood pressure response to ENaC or mineralocorticoidreceptor blockage using spironolactone and/or amiioride; to understand the role of adrenocorticalhyposensitivity in alcohol dependence, its persistence over time and relationship to subsequentalcohol intake, its emotional and structural correlates and underlying basis of reducedglucocorticoid synthesis; and to study metabolic basis of cystic fibrosis related diabetes mellitusfrom the contribution of elevated hepatic glucose production and hepatic insulin resistance.
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