Gilbert White

Thrombosis in Cancer: Research Priorities Identified by a National Cancer Institute/National Heart, Lung, and Blood Institute Strategic Working Group

Nigel Mackman, Keith R. McCrae, Gilbert White, Owen J T McCarty et autres

The risk for venous thromboembolism (VTE) is increased in cancer and particularly with chemotherapy, and it portends poorer survival among patients with cancer. However, many fundamental questions about cancer-associated VTE, or Trousseau syndrome, remain unanswered. This report summarizes the proceedings of a …

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Prothrombotic antibodies targeting the spike protein's receptor-binding domain in severe COVID-19

Wen Zhu, Yongwei Zheng, Mei Yu, Nathan Witman et autres

ABSTRACT: Thromboembolic complication is common in severe coronavirus disease 2019 (COVID-19), leading to an investigation into the presence of prothrombotic antibodies akin to those found in heparin-induced thrombocytopenia (HIT). In a study of samples from 130 hospitalized patients, collected 3.6 days after …

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A Subset of Antibodies to the Spike Protein's Receptor-Binding Domain in Severe COVID-19 Activate Platelets

Wen Zhu, Yongwei Zheng, Mei Yu, Nathan Witman et autres

Severe COVID-19 is a multisystem condition with thromboinflammation as a significant driver of morbidity and mortality. Cellular components involved in inflammatory and coagulation responses include platelets, endothelium, monocytes, and neutrophils. Thrombotic manifestations, such as arterial thrombosis, venous thromboembolism, and tissue microthrombosis, occur …

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‘Observations on Birds’

Gilbert White

Gilbert White, A Naturalist’s Calendar, with Observations in Various Branches of Natural History; Extracted from the Papers of the Late Gilbert White. Never before Published (London, B. ct J. White, 1795) , pp. 5791.

The Malmo International Brother Study (MIBS). Genetic defects and inhibitor development in siblings with severe hemophilia A

Johannes OLDENBURG, Miguel ESCOBAR, Erik BERNTORP, MIBS study group et autres

BACKGROUND AND OBJECTIVES: The strongest risk factor identified for inhibitor development in people with severe hemophilia A is the type of factor VIII gene mutation. The objective of this study was to evaluate the mutation type dependent concordance rate of inhibitor formation …

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Paxillin binding to the PH domain of kindlin‐3 in platelets is required to support integrin αIIbβ3 outside‐in signaling

Huong T. T. Nguyen, Zhen Xu, Xiaofeng Shi, Shuzhen Liu et autres

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Identification of a Novel RalGDS-related Protein as a Candidate Effector for Ras and Rap1

E G Lapetina, Teresa R. Brtva, Thomas Fischer, Daniel L. Altschuler et autres

Although Ras and Rap1 share interaction with common candidate effector proteins, Rap1 lacks the transforming activity exhibited by Ras proteins. It has been speculated that Rap antagonizes Ras transformation through the formation of nonproductive complexes with critical Ras effector targets. To understand …

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SH2- and SH3-mediated Interactions between Focal Adhesion Kinase and Src

Jeffrey W. Thomas, Byron Ellis, Renee J. Boerner, Wilson B. Knight et autres

Intramolecular SH2 and SH3 interactions mediate enzymatic repression of the Src kinases. One mechanism of activation is disruption of these interactions by the formation of higher affinity SH2 and SH3 interactions with specific ligands. We show that a consensus Src SH3-binding site …

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Relationships between Rap1b, Affinity Modulation of Integrin α IIb β 3 , and the Actin Cytoskeleton

Gilbert White, Sanford J. Shattil, Seiji Tadokoro, Alessandra Bertoni et autres

The affinity of integrin alpha(IIb)beta(3) for fibrinogen is controlled by inside-out signals that are triggered by agonists like thrombin. Agonist treatment of platelets also activates Rap1b, a small GTPase known to promote integrin-dependent adhesion of other cells. Therefore, we investigated the role …

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Expression and Function of Calcium Binding Domain Chimeras of the Integrins α IIb and α 5

Suzanne Lyman, Gilbert White, Susan Gidwitz

To further identify amino acid domains involved in the ligand binding specificity of alpha(IIb)beta(3), chimeras of the conserved calcium binding domains of alpha(IIb) and the alpha subunit of the fibronectin receptor alpha(5)beta(1) were constructed. Chimeras that replaced all four calcium binding domains, …

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G-protein binding features and regulation of the RalGDS family member, RGL2

David Magrini, Thomas Fischer, Gilbert White, Lorenza Trabalzini et autres

RGL2 [RalGDS (Ral guanine nucleotide dissociation stimulator)-like 2] is a member of the RalGDS family that we have previously isolated and characterized as a potential effector for Ras and the Ras analogue Rap1b. The protein shares 89% sequence identity with its mouse …

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SARS-CoV-2 receptor binding domain-specific antibodies activate platelets with features resembling the pathogenic antibodies in heparin-induced thrombocytopenia

Wen Zhu, Yongwei Zheng, Mei Yu, Jianhui Wei et autres

Abstract Severe COVID-19 is associated with unprecedented thromboembolic complications. We found that hospitalized COVID-19 patients develop immunoglobulin Gs (IgGs) that recognize a complex consisting of platelet factor 4 and heparin similar to those developed in heparin-induced thrombocytopenia and thrombosis (HIT), however, independent …

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