Barry Coller

..Although this preliminary tool will require validation and adjustment, we offer it to stimulate a discussion about more rigorous methods for selecting and conducting translational projects...

..Careful analysis of historical examples of abuses of human rights committed in the name of medical science or the state is an important mechanism to safeguard current and future human participants...

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..In addition, it suggests mechanistic hypotheses pertaining to both naturally occurring mutations responsible for Glanzmann thrombasthenia and to point mutations that affect ligand binding...

..Collectively, these data support RUC-1's specificity for alphaIIb, provide new insights into the alphaIIb binding pocket, and establish RUC-1's antithrombotic effects in vivo...

..Our computational results indicate that the LIMBS plays a crucial role in ligand binding to alphaIIbeta3 by virtue of its effects on the coordination of the MIDAS...

..Thus, in this model system, absence or blockade of GPIIb/IIIa receptors interferes with thrombus formation and alters the pattern of platelet deposition...

..These data suggest that the alphaIIb calcium-binding domains play a key structural role in the beta-propeller, and that the structural integrity of the calcium-binding domains is critical for integrin biogenesis...

..We conclude that 2 fundamentally different signaling mechanisms can be initiated by a single integrin receptor interacting with the same ligand when it is immobilized at different densities...

..Thus, this system can increase the power to detect genotype-phenotype-environment relationships and help new investigators begin their studies. We anticipate that this approach may be applicable to other disorders...

..Release and activation of latent TGF-beta1 in vivo was demonstrated in a mouse model 5 minutes after thrombus formation. These data potentially provide a novel mechanism for in vivo activation of TGF-beta1...

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..Our findings suggest that pro-alphaIIb engages the calnexin cycle via the N15 glycan and that failure of pro-alphaIIb to complex normally with beta3 results in proteasomal degradation...

..Thus, additional studies are needed to assess whether large platelets contribute either to pulmonary hypertension or the large vessel arterial occlusion that produces stroke in some children with sickle cell disease...

..Patient 2 had an insertion mutation resulting in a frameshift and premature termination. Both mutations affect biogenesis of platelet alphaIIbbeta3 receptors...

..Our data are consistent with alphaIIb extension resulting in increased access to the ligand-binding site and/or facilitating the conformational change(s) in beta3 that affect the intrinsic affinity of the binding pocket for ligand...

..Compound 1 provides a prototype for small molecule selective inhibition of alphaIIbbeta3, without receptor priming, via targeting alphaIIb...

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..Thus, our data are consistent with alphaIIbbeta3 existing in variably bent conformations in equilibrium with each other on unactivated platelets, and activation resulting in alphaIIbbeta3 adopting a more extended conformation...

..Our data suggest a working model in which pro-alphaIIb adopts a bent conformation soon after synthesis, and then beta3 assumes its bent conformation by virtue of its interaction with the bent pro-alphaIIb...

..These data raise the possibility that i.v.IG may have a beneficial effect on sickle cell-associated vaso-occlusion...

..Taken together, our results suggest novel testable hypotheses of intradomain and interdomain interactions responsible for beta3 integrin activation...

..In this study we show that at 23 weeks post-RIC, a leukemia patient acquired the HPA-3 donor phenotype at the DNA and platelet RNA levels...

..This interaction is less dominant when platelets adhere to fibrin, resulting in enhanced fibronectin assembly...

..In conclusion, the novel ancestral mutation found in a cluster of Jordanian GT patients disrupts a conserved Cys549-Cys558 bond which results in reduced production of constitutively active alpha IIb beta 3...

..Allostery in the head thus disrupts interaction between the legs in a previously described low-affinity bent integrin conformation, and leg extension positions the high-affinity head far above the cell surface...

..Enhancement of patency and integrity of cerebral microvessels most likely contributes to the benefits observed with this combination therapy...

..This study evaluated the role of circulating tissue factor (TF) in mediating thrombus formation on stents in an in vitro model of stent perfusion...

..Abciximab decreased the size of platelet thrombi, but did not prevent leukocyte recruitment...

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..It will also eagerly adopt the best practices identified by the Consortium and adhere to the standardsset by the Consortium. ..

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..It will also eagerly adopt the best practices identified by the Consortium and adhere to the standards set by the Consortium...

..B. The impact of breeding either P-selectin deficiency or beta3 deficiency into Berkeley sickle cell mice on erythrocyte survival, organ damage, and microvascular occlusion. ..

..The Physician-in-Chief, Dr. Barry Coller, has led the recruitments and the University Oversight of Protection of Human Subjects Committee. Dr...

..The Physician-in-Chief, Dr. Barry Coller, has led key recruitments and the University Oversight of Protection of Human Subjects Committee. Dr...

..Gordon Keller, who has agreed to train the key personnel in HESC culture techniques. Additionally, HESC culture protocols have been designed with the advice of Dr. Gordon Keller. ..

..Finally, using new high throughput technology, we hope to identify new compounds that may form the basis of improved therapies for heart attack and stroke. ..