CONTROL OF COAGULATION

  • Prendergast, Franklyn G (PI)
  • Bowie, E. J. Walter (PI)
  • Fass, David (PI)
  • Nichols, William (PI)
  • Solberg, Lawrence (PI)
  • Fuster, Valentin (PI)
  • Katzmann, Jerry (PI)
  • Mann, Kenneth (PI)
  • Bowie, E. J. Walter (PI)
  • Owen, Whyte (PI)
  • Walter Bowie, E. J. (PI)

Project: Research project

Project Details

Description

Our goal is to understand hemostatic mechanisms; improve diagnosis and
treatment of patients with hemostatic defects. The interaction of platelet
and blood vessel is being investigated in the porcine model of von
Willebrand's disease. The role of Willebrand factor in hemostasis is being
investigated at a molecular level by the use of monoclonal antibodies in
the animal and in in vitro systems. Factor VIII has been purified and its
gene has been cloned. Radiolabeled nucleotide probes will be used to
identify the cell responsible for factor VIII synthesis; the epitopes which
bind to factor IXa/X, phospholipid, Willebrand factor and protein C will be
localized by monoclonal antibodies, chemical cross-linking and with
biosynthetic peptides from genetically engineered bacteria. Information
about platelet function will be obtained by investigating platelet
activation by tannin. Tannin is responsible for byssinosis and results in
a decrease in circulating platelet numbers. This study will define the
mechanism of tannin induced signal transduction that results in the
secretion of platelet granule components. Other studies will be performed
in relation to platelet-derived microparticles which appear to result from
platelet activation processes. The production and biological role of these
microparticles will be studied as well as their occurrence in a number of
hematologic diseases. The coagulation system is implicated in the
development of infective endocarditis, although initial cellular events
that allow the development of the thrombotic lesion on the cardiac valve
and subsequent bacterial attachment are largely unknown. The role of the
platelet in the establishment of the infective lesion will be studied and
preliminary data suggest that the thrombotic lesion in the von Willebrand
pig is smaller than in the normal pig. Fundamental to an understanding of
the platelet is an understanding of megakaryocytopoiesis and this will be
described as the cells progress along the stem cell, megakaryocyte,
platelet axis. Our aim is to understand the normal mechanism by which this
pathway is regulated. Transforming growth factor B, for example, has a
remarkable inhibitory effect on committed megakaryocyte progenitors. The
project will also involve the isolation of megakaryocyte-colony stimulating
activity and the study of patients with megakaryocytic disorders. The
investigation of normal and abnormal hemostasis is designed to give greater
insight into the control of hemostasis and how symptoms arise and
laboratory tests become abnormal when the control is imperfect.
StatusFinished
Effective start/end date9/1/748/31/91

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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