Alvin Schmaier

..This study describes a novel biologic surface for FXII activation and activity, which initiates inflammatory events independent of hemostasis...

..Therefore, HK interacts with suPAR at several sites. HK binds to uPAR as part of its interaction with its multiprotein receptor complex on HUVEC, and the biological functions that depend upon this binding are modulated by urokinase...

..Understanding the interactions between these two systems may lead to development of better pharmacological treatments for endotoxin-induced shock...

..The N-terminal arginine on RPPGF binds to the P2 position or proline46 on PAR4 to block thrombin cleavage. These data indicate that RPPGF influences thrombin activity by binding to the thrombin cleavage site on both PAR4 and PAR1...

..have identified a potential reason for this - they find that in the majority of pregnant mice, anti-GPIbα antibodies enhance platelet activation and accelerate thrombus formation in the placenta and that this leads to miscarriage...

..The present characterizations of this system, which incorrectly had been thought to initiate coagulation, represent an evolution of understanding in this field...

..Better understanding of this system may lead to insight into mechanisms for arterial thrombosis, independent of hemostasis...

..These studies indicate that XII stimulates angiogenesis, a physiologic function independent of contact activation...

..It also implies that factors other than the hirudin-like binding region on PAR1 exodomain predominate in influencing PAR1 cleavage on cells...

..These combined studies suggest that FXII may become a pharmacologic target to reduce arterial thrombosis risk and promote cell repair after injury, without influencing hemostasis...

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..Insights into the integrated role of these two systems may afford the development of novel therapeutic drugs to manage hypertension and thrombosis...

..In sum, FXII initiates signaling mediated by uPAR, beta(1) integrin, and the EGFR to induce human umbilical vein endothelial cell proliferation, growth, and angiogenesis...

..These investigations indicate that rPRCP is functionally identical to isolated HUVEC PRCP and is a major HUVEC membrane-expressed, PK-activating enzyme detected in the intravascular compartment...

..Together, these results indicate that AbetaPP and APLP2 share overlapping anticoagulant functions with regard to regulating thrombosis after cerebral vascular injury...

..The K(m) of PK activation by PRCP is 6.7 nm. PRCP antigen is present on the membrane of fixed but not permeabilized HUVEC. PRCP appears to be a HUVEC-associated PK activator...

..To discuss thrombotic and hemorrhagic complications from angiogenesis inhibitors and vascular disrupting agents, pathogenesis, and recommendations for prophylaxis and management of those complications...

..One candidate may be daclizumab, especially in those with mild to moderate TMA. Rituximab therapy or the addition of defibrotide may also be beneficial. In general, plasma exchange is not recommended...

..These results suggest that a single gene, mKng1, is responsible for production of plasma kininogen, and that plasma HK contributes to induced arterial thrombosis in mice...

..This study identifies CK1 as a facilitator of MPO-mediated vascular responses and thus provides a new paradigm by which MPO affects vasoregulatory systems...

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..TH146 and MAP4-TH146 inhibit human and mouse platelet aggregation and mouse thrombosis. Analogs of RPPGF are model compounds to develop PAR1 activation antagonists as well as direct inhibitors to thrombin and factor VIIa...

..CONCLUSIONS: These data indicate that a functional PAR1 is expressed on prostate cancer cell lines. The prostate cancer cell lines expressing PAR1 appear to have an association with increased bone metastases...

..Fitzgerald DNA has a normal exon 10, but a 17-bp mutation in intron 9. These combined results indicate that mutations in the kininogen gene may differentially affect biosynthesis, processing, and/or secretion of HK...

..These studies indicate that RPPGF is a bifunctional inhibitor of thrombin: it binds to PAR1 to prevent thrombin cleavage at Arg41 and interacts with the active site of alpha-thrombin...

..PK preferential binding to endothelial cells contributes to their anticoagulant nature...

..Thus, physiologic FXII expression on HUVECs is secondary to HK binding and highly restricted in its ability to initiate prekallikrein or FXI activation...

..Most of these parameters were reversed in CLP rats that had been treated with anti-C5a. Production of C5a during sepsis may directly or indirectly cause hemostatic defects that can be reduced by blockade of C5a...

..On immunoblot, prolylcarboxypeptidase antigen is associated with HUVEC matrix. These studies indicate that prolylcarboxypeptidase is the matrix PK activator...

..5x (P<0.03) using laser-light scattering and platelet adhesion by 1.8x (P<0.02). CONCLUSION: Thrombostatin or aspirin independently decreases evidence of platelet activation in the canine carotid artery model of BA injury...

..Factor V(Leiden) (fV(Leiden)) predisposes to thrombosis by enhancing thrombin formation. This study tested the hypothesis that fV(Leiden) inhibits fibrinolysis in vivo...

..This analysis suggests that there is a multilayered interaction between these two systems that are important for a wide array of physiological functions...

..Our studies indicate that different proteins generate different SFG amide signals at the polystyrene/protein solution interface, showing that they have different interfacial coverage, secondary structure, or orientation...

..These investigations indicate that negatively charged surfaces facilitate or induce FXII autoactivation on the molecular level by imposing specific orientation and ordering on the adsorbed protein molecules...

..These investigations indicate a pathway for thrombosis risk reduction via the plasma kallikrein/kinin and renin angiotensin systems...

..Our intent is to stimulate interest in the development of professional guidelines for platelet function testing in the clinical laboratory...

..These studies suggest that the efficiency of T. cruzi to initiate kinin release is potently enhanced by the mutual interactions between cruzipain, HK, and heparan sulfate proteoglycans...

..The proposal aims to characterize the first recognized prothrombotic mouse due to increased reactive oxygen therapy. Studies will also examine if the prothrombotic and hypertensive mechanisms are linked. ..

..These investigations will lead to the recognition of new targets for drug development that could be used to treat hypertension and decrease thrombosis risk. ..

..Second, the preparation of an IND application for its human use for one indication will be achieved. Thrombostatin(tm) has the opportunity to be a first-in-its-class thrombin receptor activation antagonist. ..

..These studies are intended to characterize this system's contribution to vascular biology and to develop new strategies to modulate intravascular thrombosis. ..

..These studies could serve as a basis for the development of a global assay(s) to predict the prothrombotic state in man. (End of Abstract.) ..

..Modulation of bradykinin liberation is important in the regulation of local blood pressure in coronary, renal, pulmonary, and cerebral circulations. ..