The theme focuses on viral infections and immune responses associated with transfusion of blood. An integrated program of 7 basic and clinical research projects, aided by two specialized core units, is designed to investigate the contemporary problems of transfusion-transmitted hepatitis, CMV, and AIDS, and resulting effects on the immune system. The molecular mechanisms of pathogenesis of post-transfusion hepatitis caused by hepatitis viruses as well as the non-A, non-B viruses are to be investigated through prospective studies in transfused patients and experimental studies in animal models which will also be used in study of antiviral agents against hepatotropic viruses (Projects 1 and 2). Immunologic mechanisms in post-transfusion CMV infection, in donor-specific transfusions prior to renal transplantation and immunosuppressive effects per se of homologous versus autologous blood transfusions will be studied in Projects 3, 4 and 5. The problems of transfusion-associated AIDS are addressed in culturing the virus for definition of infection versus immunity to the virus in antibody positive blood donors (project 6) and in deriving animal models for therapeutic and preventive measures against the AIDS retrovirus (ARV/LAV/HTLV III) infection (project 7). The specific expertise in viral immunology, molecular hybridization analyses with cloned DNA probes, flow-cytometry for cell-surface marker analyses with monoclonal antibodies and cell sorting in experimental cell biology studies are made available to all investigators by the Core Units A and B. The ultimate goal is to prevent transmission of the blood borne viral infection and managing the unresolved infection with antiviral therapy. This goal will be achieved by promoting interaction between the investigators and by using the clinical resources of the University of California Hospitals, the Mount Zion Medical Center and the Irwin Memorial Blood Bank in San Francisco. The program complements and strengthens the academic commitment of UCSF faculty to excellence in teaching, research and service in transfusion medicine.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL036589-03
Application #
3098549
Study Section
Heart, Lung, and Blood Research Review Committee B (HLBB)
Project Start
1986-07-01
Project End
1991-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Ulrich, P P; Romeo, J M; Daniel, L J et al. (1993) An improved method for the detection of hepatitis C virus RNA in plasma utilizing heminested primers and internal control RNA. PCR Methods Appl 2:241-9
Castro, B A; Homsy, J; Lennette, E et al. (1992) HIV-1 expression in chimpanzees can be activated by CD8+ cell depletion or CMV infection. Clin Immunol Immunopathol 65:227-33
Evans, C S; Tobler, L; Polito, A et al. (1992) Comparative evaluation of supplemental hepatitis C virus antibody test systems. Transfusion 32:408-14
de Lomas, J G; Sunzeri, F J; Busch, M P (1992) False-negative results by polymerase chain reaction due to contamination by glove powder. Transfusion 32:83-5
Busch, M P; Lee, T H; Heitman, J (1992) Allogeneic leukocytes but not therapeutic blood elements induce reactivation and dissemination of latent human immunodeficiency virus type 1 infection: implications for transfusion support of infected patients. Blood 80:2128-35
Eble, B E; Busch, M P; Khayam-Bashi, H et al. (1992) Resolution of infection status of human immunodeficiency virus (HIV)-seroindeterminate donors and high-risk seronegative individuals with polymerase chain reaction and virus culture: absence of persistent silent HIV type 1 infection in a high-prevalence a Transfusion 32:503-8
Busch, M P; el Amad, Z; McHugh, T M et al. (1991) Reliable confirmation and quantitation of human immunodeficiency virus type 1 antibody using a recombinant-antigen immunoblot assay. Transfusion 31:129-37
Sunzeri, F J; Lee, T H; Brownlee, R G et al. (1991) Rapid simultaneous detection of multiple retroviral DNA sequences using the polymerase chain reaction and capillary DNA chromatography. Blood 77:879-86

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