The major objective of this research proposal is to study the basic biological processes involved in the regulation and control of the blood fibrinolytic system in health and disease. This program will deal with the identification of abnormal plasminogens found in the plasmas of patients with thrombotic diseases. The variant plasminogens will be isolated and characterized by physical and chemical methods; the molecular defect, perhaps a single amino acid substitution, will be determined using classical protein chemistry methods. The plasminogen defect is present in the plasminogen gene itself and is produced by either a single base-pari change, or a larger structural change in the gene, and this defect is inherited in a Mendelian fashion. The plasminogen gene map and the plasminogen cDNA (clone) will be used in these studies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL034276-08
Application #
3347010
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1989-01-01
Project End
1994-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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Robbins, K C; Boreisha, I G; Godwin, J E (1991) Abnormal plasminogen Maywood I. Thromb Haemost 66:575-80
Robbins, K C (1990) Classification of abnormal plasminogens: dysplasminogenemias. Semin Thromb Hemost 16:217-20
Lee, P P; Wohl, R C; Boreisha, I G et al. (1988) Kinetic analysis of covalent hybrid plasminogen activators: effect of CNBr-degraded fibrinogen on kinetic parameters of Glu1-plasminogen activation. Biochemistry 27:7506-13
Robbins, K C; Barlow, G H; Nguyen, G et al. (1987) Comparison of plasminogen activators. Semin Thromb Hemost 13:131-8
Robbins, K C; Boreisha, I G (1987) A covalent molecular weight approximately 92,000 hybrid plasminogen activator derived from human plasmin fibrin-binding and tissue plasminogen activator catalytic domains. Biochemistry 26:4661-7
Summaria, L; Boreisha, I; Barlow, G H et al. (1987) The isolation and characterization of a ternary human plasmin B-chain-streptokinase-plasminogen complex. Thromb Haemost 58:772-7
Scharrer, I M; Wohl, R C; Hach, V et al. (1986) Investigation of a congenital abnormal plasminogen, Frankfurt I, and its relationship to thrombosis. Thromb Haemost 55:396-401
Toki, N; Sumi, H; Sasaki, K et al. (1985) Transport of urokinase across the intestinal tract of normal human subjects with stimulation of synthesis and/or release of urokinase-type proteins. J Clin Invest 75:1212-22