Abstract

The long term goal of the proposed research is increased understanding of certain aspects of fibrinogen biosynthesis, the carbohydrate content (sialic acid) of fibrinogen and its relationship to synthesis. Studies are designed to increase understanding of the basic mechanisms involved in the regulation of fibrinogen synthesis by parenchymal cells of the liver. Particular attention will be directed at the mechanism by which the plasma degradative fibrinogen fragments D and E increase the synthesis of fibrinogen in the intact rabbit. To directly answer this question, the hepatic parenchymal cells will be isolated and studied in a controlled environment, in vitro. Of particular interest is the observation that fibrinogen fragments D and E stimulate fibrinogen synthesis, while the same fragments from fibrin do not. Studies have been designed to determine whether the polypeptide or carbohydrate portion of fragments D and E are responsible for their stimulatory capacity. These studies will provide further understanding of fibrinogen biosynthesis and the clottability of this protein.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL024898-05
Application #
3337888
Study Section
(EH)
Project Start
1981-09-30
Project End
1986-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Bell, W R (1995) Laboratory monitoring of thrombolytic therapy. Clin Lab Med 15:165-78
Brandao-Neto, J; Bell, W R (1994) Characteristics of zinc binding to human red blood cell membranes. Am J Hematol 45:1-9
Bell, W R (1994) Thrombolytic therapy. Agents, indications, and laboratory monitoring. Med Clin North Am 78:745-64
Rosenfeld, B A; Beattie, C; Christopherson, R et al. (1993) The effects of different anesthetic regimens on fibrinolysis and the development of postoperative arterial thrombosis. Perioperative Ischemia Randomized Anesthesia Trial Study Group. Anesthesiology 79:435-43
Lankiewicz, M W; Bell, W R (1992) A unique circulating inhibitor with specificity for coagulation factor X. Am J Med 93:343-6
Bell, W R; Braine, H G; Ness, P M et al. (1991) Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients. N Engl J Med 325:398-403
Lekstrom, J A; Bell, W R (1991) Aspirin in the prevention of thrombosis. Medicine (Baltimore) 70:161-78
Gray, W J; Bell, W R (1990) Fibrinolytic agents in the treatment of thrombotic disorders. Semin Oncol 17:228-37
Noe, D A; Murphy, P A; Bell, W R et al. (1989) Acute-phase behavior of factor VIII procoagulant and other acute-phase reactants in rabbits. Am J Physiol 257:R49-56
Schmelzer, C H; Ebert, R F; Bell, W R (1989) Fibrinogen Baltimore IV: congenital dysfibrinogenemia with a gamma 275 (Arg----Cys) substitution. Thromb Res 56:307-16

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