Abstract

Our long-term objective is to provide clinical and basic research and train at this Medical Center on the pathophysiology, diagnostic skill, and management of a variety of hemostatic and thrombotic disorders although our current proposal will focus on the microcirculation disorders such as thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), progressive sclerosis, and multiple sclerosis.
The specific aims of this proposal include: 1) purification and characterization of platelet aggregating factor in the TTP plasma and study of its interaction with platelets: 2) development of a sensitive immunoassay for TTP-PAF: 3) determination of the role of F VIII:vWF complex, PGI2, fibrinolytic activity and immune response in TTP; 4) study of the vivo effect of TTP plasma in animal models and therapeutic efficacy of various therapeutic agents; and 5) study of the effect of sera from patients with TTP, HUS, scleroderma, and multiple sclerosis on the endothelial cells, including cytotoxicity and fibrinolytic activity. The methods which will be used for the projects include conventional protein purification and characterization methods, immunoelectrophoresis, radioimmunoassay, platelet aggregation studies, fibrinolytic activity study, PGI2 bioassay and immunoassay, monoclonal antibody production, infusion of TTP plasma into mice, light and immunofluorescence microscopy, and electron microscopy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL027007-06
Application #
3338843
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1981-09-30
Project End
1988-07-31
Budget Start
1986-09-01
Budget End
1988-07-31
Support Year
6
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Miami School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
Miami
State
FL
Country
United States
Zip Code
33101

  Publications

Yu, A X; Wu, X W; Li, J Z et al. (1993) Mechanism of platelet aggregation induced by a monoclonal antibody requiring Fc portion. Thromb Res 70:51-65
Siddiqui, F A; Lian, E C (1993) Characterization of platelet agglutinating protein p37 purified from the plasma of a patient with thrombotic thrombocytopenic purpura. Biochem Mol Biol Int 30:385-95
Siddiqui, F A; Lian, E C (1992) Platelet-agglutinating protein p37 from a thrombotic thrombocytopenic purpura plasma forms complexes with platelet membrane glycoprotein IV (CD36). Biochem Int 27:485-96
Lian, E C; Siddiqui, F A; Jamieson, G A et al. (1991) Platelet agglutinating protein p37 causes platelet agglutination through its binding to membrane glycoprotein IV. Thromb Haemost 65:102-6
Lian, E C; Siddiqui, F A (1991) Binding of platelet agglutinating protein p37 from the plasma of a patient with thrombotic thrombocytopenic purpura to human platelets. Thromb Haemost 65:96-101
Li, J Z; Liu, J W; Benito, G et al. (1989) Electron microscopic study of platelet agglutination induced by thrombotic thrombocytopenic purpura plasma containing 37-KDa platelet agglutinating protein. Thromb Res 55:757-66
Lian, E C; Larcada, A F; Chiu, A Y (1989) Combination immunosuppressive therapy after factor VIII infusion for acquired factor VIII inhibitor. Ann Intern Med 110:774-8
Li, J Z; Lian, E C (1988) Mechanism of rabbit platelet agglutination induced by acidic mucopolysaccharide extracted from Stichopus japonicus Selenka. Thromb Haemost 59:432-4
Siddiqui, F A; Lian, E C (1988) Platelet-agglutinating protein P37 from a thrombotic thrombocytopenic purpura plasma forms a complex with human immunoglobulin G. Blood 71:299-304
Li, J Z; Lian, E C (1988) Aggregation of human platelets by acidic mucopolysaccharide extracted from Stichopus japonicus Selenka. Thromb Haemost 59:435-9

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