Tobacco Documents Online

I THE COIINCIL FOR TOBACCO RESEARCH-U.S.A., INC. Septenber 4, 1984 Site Visit Date of visit: 8/22/84 Grantee: R.W. Colman, M.D., Temple University School of Medicine, Philadel- phia, PA. Grant No. 1420R2 "Initiation of Plasm Coagulation and Kixiin-Form.ing Systems in Man" Site-Visitor: David Stone Background: Dr. Colman has been supported (Grant 1420 and renewals).on this project for the past 2 1/2 years. In that period this productive investigator has published 18 articles (see attachment "Specific Aims - Jan. 1, 1982 through Dec. 30, 1984), covering the aims outlined in his original application. Dr. Coleman has applied for a Continuation Application of the same title as above (No. 1420A) which will be considered at.the SAB meeting in September 1984. Discussion: Dr. Colman and his co-workers (including Drs. Sclmiaier and Veloso) are interested in surface-mediated defense reactions against injury (blood coagulation, inflamnatory response, fibrinolysis, ccaT:C.exnent pathway activa- tion), initiated, amplified and propagated by the zynagens Factor XII (Hageman Factor), Prekallikrein, High Molecular Weight Kininogen and Factor XI. Their efforts are involved in the elucidation of activation of these zym:)gens by limited proteolysis to the active serine proteases XIIa, kallikrein and XIa by auto-activation on negatively charged surfaces in. the presence of high MW Kininogen as non-enzymatic cofactor, and their involvements in activation of Cl, Factor VII,prorenin and plasminogen, as well as their interactions and feedbacks in self-regulation systems. Colman is interested in effects of negatively.charged, active surfaces on the kinetics of reactions, as well as in the develoFxnent of accurate assays (imnunochemical) of the caiiponents of the "contact systetn" (high MW kininogen, C1-inY-..ibitor, Factor Vii, kalikrein, Factor XI and kininogen peptide), and their detection by monoclonal antibodies. Having obtained accurate assays, Colman's interest is to investigate contact system activations in diseases including adult RDS, nephrotic syndrane and others. Further important areas of study will involve: (a) Interactions of contact system proteins with platelets, not only as providers of surface for activation of intrinsic coagulation, but also of platelet activation of zymogens; (b) Inter- action of neurophils with enzymes of the contact system in elastase release and H2O2 and oxygen radical production. Conclusion: A productive and impressive investigator whose group appeared to be at the forefront of this important area of research. Of special interest are the possible relationships of kallikrein as chemotactic agent and neutrophil .

-2- activator in elastase secretion and in H202 and oxygen radical production: that is, of injury to the oontact systen leading to factors which might be involved in the genesis of emphysena and/or cancer. Attachments: List of~publications 2. American Heart Association Meeting, Novembex 14, 1984 3. International Coimtittee on Thrcmbosis and Hemostasis Novanber 16, 1984 David Stone