Abstract

. The objective of this project is to continue examination of the processes of blood coagulation and related phenomena with an increasing emphasis on the regulatory role of blood cells and endothelial cells. Our focus will be on regulation of the initial steps of clotting via the intrinsic pathway of thrombin formation, particularly upon control of the activation of Hageman factor (factor XII). Our immediate goal is to elucidate the role of inhibitors of the activation of this clotting factor that are derived from vascular endothelial cells. We will also explore the importance of metallic ions in activation of Hageman factor. These and related projects aim at an understanding of hemorrhagic and thrombolytic states. As always, vigorous attempts will be made to learn more about the physiology of hemostasis and thrombosis through study of suitable patients.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL001661-42
Application #
3334110
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1975-09-01
Project End
1995-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
42
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106

  Publications

Bogdan, C J; Strauss, M; Ratnoff, O D (1994) Airway obstruction in hemophilia (factor VIII deficiency): a 28-year institutional review. Laryngoscope 104:789-94
Pettee, A D; Wasserman, B A; Adams, N L et al. (1994) Familial Sneddon's syndrome: clinical, hematologic, and radiographic findings in two brothers. Neurology 44:399-405
Perales, J C; Ferkol, T; Beegen, H et al. (1994) Gene transfer in vivo: sustained expression and regulation of genes introduced into the liver by receptor-targeted uptake. Proc Natl Acad Sci U S A 91:4086-90
Ratnoff, O D; Gleich, G J; Shurin, S B et al. (1993) Inhibition of the activation of hageman factor (factor XII) by eosinophils and eosinophilic constituents. Am J Hematol 42:138-45
Ferkol, T; Lindberg, G L; Chen, J et al. (1993) Regulation of the phosphoenolpyruvate carboxykinase/human factor IX gene introduced into the livers of adult rats by receptor-mediated gene transfer. FASEB J 7:1081-91
Stein, J; Ratnoff, O D (1993) An inhibitor of antihemophilic factor (factor VIII) in an 18-month-old nonhemophilic child. Am J Pediatr Hematol Oncol 15:346-50
Ratnoff, O D (1993) Some complications of the therapy of hemorrhagic disorders. Dis Mon 39:301-54
Ryder, J; Everson, B; Jentoft, J et al. (1993) The effect of chemical modification of basic amino acid residues on the activation and amidolytic activity of Hageman factor (factor XII). J Lab Clin Med 122:697-702
Foster, C B; Flanigan, T P; DeStigter, K K et al. (1992) Inhibition of the activation of Hageman factor (factor XII) by extracts of Schistosoma mansoni. J Lab Clin Med 120:735-9
Toossi, Z; Sedor, J R; Mettler, M A et al. (1992) Induction of expression of monocyte interleukin 1 by Hageman factor (factor XII). Proc Natl Acad Sci U S A 89:11969-72

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