FELLOWSHIP FOR Alikhan: ACR REF Amgen/Pfizer Rheumatology Fellowship Training Award

HDL Metabolism in Rheumatoid Arthritis: Our hypothesis is that RA disease activity correlates with lower antioxidative capacity and dysfunctional lipid profile favoring atherogenesis, and the initiation of methotrexate will lead to improvement. Measures include overall lipid profile, PON1 activity, PAF-AH, and serum amyloid A. Cellular cholesterol efflux to RA serum is measured using 3H-cholesterol in cells transfected with specific transporters. RA disease activity will be followed clinically by using DAS28 score and inflammatory cytokines. Skeletal Muscle in RA: The hypothesis is that skeletal muscle from patients with RA will show evidence of oxidative stress-related disease activity compared with healthy controls. These histologic findings will be associated with decreased muscle strength and endurance. We will obtain muscle biopsies to compare contractile function of permeabilized muscle fibers and biochemical markers of oxidative stress including glutathione derivatives and protein oxidation adducts, as well as sphingomyelinase activity. We will correlate the findings in skeletal muscle with RA disease activity as measured by DAS28 , serum proinfiammatory cytokines, muscle mass and strength (DXA and dynamometer), and measures of fatigue, physical function, and health-related quality of life. The Role of Clock Genes in Sleep, Fatigue, and Circadian Rhythms: The specific objectives of this study are to correlate peripheral and central circadian rhythms to sleep quality and fatigue. PartiCipants will have a one-week lead-in using actigraphy, temperature probe, and daily diaries. They will be admitted to the inpatient CRC for hourly peripheral blood collection. PBMC will be