MULTIPURPOSE ARTHRITIS & MUSCULOSKELETAL DISEASES CENTER

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This application requests continued support for the Multipurpose Arthritis Center (MAC) in San Diego, California. The collaborating investigators in the Center were previously based at the Scripps Clinic and Research Foundation and at San Diego State University, under the directorship of Dr. Eng M. Tan. Dr. Tan has now transferred the directorship of the Center to Dr. Dennis A. Carson, the director of the Research Component. Since Dr. Carson, and Dr. Robert Kaplan, the director of the Health Services and Education Component, have accepted faculty appointments at the University of California, San Diego (UCSD), the MAC will now be based at this site. The new Center will have greatly expanded facilities, and will include the participation of the Rheumatology Division at the UCSD School of Medicine, the Department of Mathematics and Biostatistics, and the Department of Community and Family Medicine. The MAC is divided into three parts: (1) the Cores; (2) the Research Component; and (3) the Health Services and Education Component. The Cores provide services necessary for the proper functioning of the Research and Health Services and Education components of the Center, and in addition foster interactions among the participating faculty. They consist of (1) an Executive Committee that will be responsible for the scientific direction of the center, (2) an Administrative Core that will plan, develop, and coordinate the ongoing activities of the center, (3) a Clinical core that will recruit and evaluate patients, and that will obtain clinical samples for individual investigators, (4) a Molecular Biology Core that will serve as a shared resource for oligonucleotide synthesis, vector preparation, and training in basic molecular biology techniques, and (5) a Biostatistics Core that will assist in the design, analysis, and evaluation of experimental protocols. The Research Component contains six separate projects: (1) a biochemical and immunologic analysis of the effects of a new anti-monocyte/macrophage agent (2-chlorodeoxyadenosine) in patients with rheumatoid arthritis, (2) a functional and molecular analysis of the autoepitopes on the SS-B/La autoantigen, (3) an analysis of cytokine expression in the synovial tissues from patients with rheumatoid arthritis, using in situ hybridization, (4) a detailed evaluation of a new animal model of systemic autoimmunity induced by mercuric chloride, (5) a dissection of the mechanism by which the HLA Dw4 antigen influences the immune response to the Epstein-Barr virus, and (6) a molecular analysis of the relationship between anti- carbohydrate antibodies and autoantibodies in humans. The Health Services and Education Component contains four separate projects: (1) an investigation of prospective predictors of musculoskeletal problems in a large middle-class retirement community in the San Diego area, (2) an analysis of the impact of musculoskeletal problems on health policy, (3) a trial of the benefits of behavioral interventions for patients with the fibrositis syndrome, and (4) a study of the relationship between learned helplessness and response to methotrexate in patients with rheumatoid arthritis. The new MAC includes individuals with experience and expertise in basic research, health services research, and medical education. Through the auspices of the Center, these individuals will interact to foster arthritis research, training, and education in the growing San Diego community.