The hypothesis to be tested within this clinical Core and in Projects 1, 2 & 3 is that TA is triggered by HCMV. The projects will examine the direct and indirect effects of HCMV specifically focusing on how adaptive immune response to virus modulates the eNOS pathway. Because the various immunological and functional assays proposed in the individual projects will be correlated with TA in patients, and individual blood samples and heart biopsy specimens will be divided among the individual Principal Investigators for each project, we are proposing a Clinical Research Support Core. The Clinical Research Support Core will consist of Patient Management Core; Coronary Artery Disease Quantitation Laboratory; Specimen Processing, Virology/Immunopathology Laboratory; and Database Management Core. The function of the Clinical Research Support Core is to recruit subjects and assure that subjects? rights are respected; administer the protocol to ensure standardization of patient care, protocol adherence and long term follow-up; obtain quantitative data regarding progression to TA; provide centralized processing of blood and heart biopsy specimens (EMB); perform virological studies (culture and PCR); maintain a centralized database Clinical and laboratory results; and perform statistical analysis and modeling on the data. To aid in the recruitment of heart transplant patients we have established collaborations with one other heart transplant center (Cleveland Clinic) with whom we have a track record of collaborative research. The Coronary Artery Disease Quantitation Laboratory of the Clinical Research Support Core will implement protocols for intracoronary ultrasound recordings and analysis used in tracking progression to TA. The Virology/Immunopathology Laboratory will be composed of: 1) The specimen processing unit which will utilize a computer supported tracking system for logging and distribution of specimens to individual Project Principal Investigators. 2) A cell culture facility to maintain endothelial, smooth muscle, fibroblasts, and monocytes necessary to support all projects. 3) A virology unit to culture and isolate CMV from patient samples, and to perform assays to quantitate viral load. 4) An immunopathology unit to characterize the inflammatory cells and microvascular changes on EMB, extraction of nucleic acids, and determination of cytokine gene expression by in situ hybridization. A centralized database will be developed to capture clinical and assay information for analysis. The Clinical Research Support Core will allow for clinical study of the-subjects, the most efficient utilization of limited patient samples; and analysis of the combined data I obtained from clinical study as well as the results obtained from the individual projects.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
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Stanford University
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