EXCEED THE SPACE PROVIDED. The Washington University General Clinical Research Center (GCRC) supports and facilities patient-oriented research and research training at Washington University School of Medicine. The GCRC includes an Adult Unit (outpatients and inpatients) in Barnard Hospital (operated by Barnes-Jewish Hospital) and a Pediatric Unit (outpatients) in St. Louis Children's Hospital. It provides research nursing, bionutrition, core laboratory, informatics and biostatistical support. New ventures include a substantially expanded training program including development of a School-wide Division of Clinical Sciences, a new GCRC Pharma-cogenetics Core, planning for a clinical research imaging center and implementation of the GCRC Data and Safety Monitoring Plan. This application requests five years of support for the GCRC for its 44 ththrough 48 thyears. The 116 protocols in this application are led by 46 GCRC principal investigators with appointments in the Departments of Medicine, Pediatrics, Surgery, Neurology, Psychiatry, Radiology, Pathology, Cell Biology and Physiology, Molecular Biology and Pharmacology and Genetics. While there are a broad range of approaches, many protocols require complex, research procedures including clamps, tolerance tests, tissue microdialysis, stable and radioactive kinetics (e.g., glucose, fatty acids, glycerol, amino acids, neuro-transmitters) and indirect calorimetry as well as pharmacokinetics. Techniques used include genotype-phenotype correlation, an array of imaging methods including positron emission tomography, NMR imaging and spectroscopy and fMRI, and mass spectroscopy as well as tissue biopsies (muscle, fat, bronchi) for molecular analyses. The diseases/disorders under study include AIDS (CNS and metabolic complications, treatment), Aging (sarcopenia, osteopenia, heart disease, caloric restriction), Alzheimer disease, Asthma (pathogenesis, management), Coronary Artery Disease (prevention, treatment), Cystic Fibrosis (neutrophil function, energy balance), Depression (CNS mechanisms, treatment), Diabetes (genetics, pathogenesis, prevention, islet transplantation, treatment, complications including hypoglycemia, psychosocial factors, heart disease), Dyslipidemias (fatty liver, treatment), End-Stage Renal Disease (bone disease, transplantation), Hypertension (LVH, treatment), Osteoporosis (genetic mechanisms, prevention, treatment), Obesity (pathogenesis, treatment, fatty liver, lipid metabolism, heart disease), Prostate Cancer (screening, bone disease), Multiple Sclerosis (treatment), and Schizophrenia (treatment, complications) among others.