This is a proposal for continuation of a Program Project Grant to study fundamental and clinical aspects of coagulation, including cellular and clotting factor interactions, fibrin formation, thrombus prevention and thrombolytic therapy.
Specific aims of basic studies are to determine the role of the amino-terminus of the fibrin Beta chain in mediating platelet and endothelial call spreading, adhesion and platelet activation and to determine the role of fibrin crosslinking on platelet and endothelial cell spreading to determine conformational structures of the alpha chain residues of fibrinogen that interact with rickettsial organisms and to determine whether such changes occur ax vivo in umbilical cored vessels an underlie the vascular thrombosis that occurs in animals with rickettsial infection, and to study the macromolecular interactions of human factor VIII thrombin, vonWillabrand factor, and factor IXa and phospholipid, Clinical studies will develop new approaches which optimize clinical thrombolysis, emphasizing the potential of lym- plasminogen administration in randomized clinical trials of patients with acute myocardial infraction and peripheral arterial occlusion, assess the potential of a non-invasive tests for thrombolysis, specifically magnetic resonance imaging and a modified D-dimer assay that accounts for degradation of soluble fibrin, and maximize the application of thrombolytic therapy to appropriate patients, especially women, by educational progress in university and community hospital. The five research projects will be supported by two core facilities devoted to administration (Core A) and tissues culture (Core B). The program emphasizes a balance between the expertise of fundamental and clinical scientists working independently and in concert with each other, and in the bidirectional flow of ideas and data between the laboratory bench and the hospital bed.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
2P01HL030616-11A1
Application #
2216670
Study Section
Heart, Lung, and Blood Research Review Committee B (HLBB)
Project Start
1983-07-01
Project End
1999-03-31
Budget Start
1994-04-15
Budget End
1995-03-31
Support Year
11
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Rochester
Department
Internal Medicine/Medicine
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Sahni, Sanjeev K; Rydkina, Elena (2009) Host-cell interactions with pathogenic Rickettsia species. Future Microbiol 4:323-39
Sahni, Abha; Arévalo, Maria T; Sahni, Sanjeev K et al. (2009) The VE-cadherin binding domain of fibrinogen induces endothelial barrier permeability and enhances transendothelial migration of malignant breast epithelial cells. Int J Cancer 125:577-84
Sahni, Sanjeev K; Rydkina, Elena; Sahni, Abha (2008) The proteasome inhibitor MG132 induces nuclear translocation of erythroid transcription factor Nrf2 and cyclooxygenase-2 expression in human vascular endothelial cells. Thromb Res 122:820-5
Sahni, A; Simpson-Haidaris, P J; Sahni, S K et al. (2008) Fibrinogen synthesized by cancer cells augments the proliferative effect of fibroblast growth factor-2 (FGF-2). J Thromb Haemost 6:176-83
Mosesson, M W; Hernandez, I; Raife, T J et al. (2007) Plasma fibrinogen gamma'chain content in the thrombotic microangiopathy syndrome. J Thromb Haemost 5:62-9
Rydkina, Elena; Sahni, Abha; Baggs, Raymond B et al. (2006) Infection of human endothelial cells with spotted Fever group rickettsiae stimulates cyclooxygenase 2 expression and release of vasoactive prostaglandins. Infect Immun 74:5067-74
Sahni, Abha; Khorana, Alok A; Baggs, Raymond B et al. (2006) FGF-2 binding to fibrin(ogen) is required for augmented angiogenesis. Blood 107:126-31
Duan, Hai Ou; Simpson-Haidaris, Patricia J (2006) Cell type-specific differential induction of the human gamma-fibrinogen promoter by interleukin-6. J Biol Chem 281:12451-7
Rydkina, Elena; Silverman, David J; Sahni, Sanjeev K (2005) Activation of p38 stress-activated protein kinase during Rickettsia rickettsii infection of human endothelial cells: role in the induction of chemokine response. Cell Microbiol 7:1519-30
Clifton, Dawn R; Rydkina, Elena; Freeman, Robert S et al. (2005) NF-kappaB activation during Rickettsia rickettsii infection of endothelial cells involves the activation of catalytic IkappaB kinases IKKalpha and IKKbeta and phosphorylation-proteolysis of the inhibitor protein IkappaBalpha. Infect Immun 73:155-65

Showing the most recent 10 out of 268 publications