A T Nurden

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..Immunolocalization showed VWF not only associated with platelets, but already on the megakaryocyte surface and within internal channels. In this family, type 2B VWD is clearly associated with abnormal platelet production...

..We conclude that R763G is a new type 2N VWD mutation located in the VWF propeptide which alters the proteolytic processing of VWF and consequently its binding to FVIII...

..Our purpose is to review the mutations in the ITGA2B and ITGB3 genes that lead to anisotropy and to discuss mechanisms by which this can be brought about...

..Modelling strongly suggested that both mutations act by destabilizing the αIIb beta propeller. So it appears likely that this patient has a combination of co-expressed genetic defects...

..The above mentioned roles of platelets are now discussed...

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..Knowledge of the mutation in GT and whether it affects either of the ITGA2B or ITGB3 genes will be essential as we enter the period where accurate prenatal diagnosis and gene therapy may become viable options...

..However, long-term side-effects are being assessed and the exact role of these agents in the overall treatment strategy of chronic idiopathic thrombocytopenic purpura remains to be established...

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..We now review the ways in which platelets participate in these processes...

..Our studies highlight an unusual mixture of defects giving rise to severe bleeding in a child and describe the first pathological missense mutation affecting a C-terminal residue of the calf-2 domain of alpha(IIb)...

..In this review, we document the clinical and molecular heterogeneity in GPS, a unique disease of the biogenesis of platelet alpha-granules and of the storage of growth factors and secretable proteins...

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..To overview inherited syndromes that affect platelets and to discuss current data on the molecular origin and management of these rare diseases...

..Administration of recombinant factor VIIa is an increasingly used therapeutic alternative. GT can be a severe hemorrhagic disease, however the prognosis is excellent with careful supportive care...

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..Platelet disorders are examples of rare diseases; nevertheless they have provided essential information in the elucidation of the molecular basis of platelet function...

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..Thus platelets of some fibrinolytic patients have an increased tendency for surface activation within the first 72 h after treatment, a finding which would be compatible with an increased thrombotic tendency...

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..Our results therefore show that two-way trafficking of adhesion receptors can occur during platelet activation. This would imply that GP Ib-IX and VLA-2 are attached to different elements within the membrane cytoskeleton...

..It was a T --> C base transition at position 1787 of GPIIb cDNA and results in a Ile565 to Thr substitution. The two GPIIb mutations identified in this study will provide new information on GPIIb-IIIa structure and biosynthesis...

..Activated platelets may play a role in constituting acute occlusion by thrombosis but their detection was not predictive of restenosis...

..In rare cases of immune thrombocytopenic purpura (ITP), autoantibodies to GPVI result in receptor shedding. Objectives: To investigate a possible pathogenic role of plasma anti-GPVI antibody located in a woman with lupus nephritis...

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..In vivo experiments in atherosclerotic rabbits followed by immunohistological analysis, revealed a specific binding of XIIF9 on platelets engaged in thrombus formation, demonstrating real clinical potential for such MAbs in imaging...

..The expression product in Escherichia coli was a 35 kDa scFv fragment with the antigen-binding specificity of the parental mAb...

..Stem cell or bone marrow transplantation has been successful for several diseases while gene therapy shows promise in the Wiskott-Aldrich syndrome...

..This new procedure is simple, safe and inexpensive; it provides extra security for patients with a bleeding risk undergoing dentistry or superficial surgery...

..Five antibodies were platelet-activating. In conclusion, the mechanisms responsible for this complication of anti-aIIbb3 therapy are multiple and often associated with a complex immune response...

..This article highlights the use of this technology and discusses some of the obstacles and challenges that need to be addressed to maintain progress in this field...

..For both patients a single mutated allele was inherited from each parent. Evidence is accumulating that nonsense mutations leading to a truncated beta3 may be a frequent cause of type I Glanzmann thrombasthenia in the Iberian peninsula...

..Our aim is to review these advances and discuss the ways in which platelets may provide such unexpected beneficial therapeutic effects...

..Thus, a single amino acid substitution in the extracellular domain of GPIbbeta can affect both the maturation of GPIbalpha and GPIX stability. GPIbbeta has a pivotal role in regulating GPIb-IX-V biosynthesis...

..Pharmacologic antagonism of ADP or TXA(2) receptors in antithrombotic therapy may need to take into account blockade of internal receptor pools...

..Our studies implied that alphaIIbbeta3 in platelets may bind fibrinogen in different activation states and that this patient specifically lacked high-affinity binding...

..Thus ILK transiently associates with and phosphorylates beta3 in a PI3-kinase dependent manner suggesting that it participates at an intermediate stage in a critical mechanism for assuring large stable aggregates...

..This was confirmed by complete inhibition on the addition of creatine phosphate/creatine phosphokinase...

..To study how giant platelets are produced in vivo, we used a model of GPIbalpha-deficient mice (GPIbalpha(null)) and mice rescued with the human GPIbalpha transgene (GPIbalpha(null;hTg))...

..In conclusion, platelets appear as a reservoir of CD40L that may be a major contributor to circulating sCD40L. Platelet-associated CD40L may be a potential marker of platelet regeneration...

..Our results may provide a molecular explanation for the subgroup of patients with severely deficient collagen-induced platelet aggregation as previously described for GPS in the literature...

..We examined whether platelets could activate mesangial cells and the potential role of the platelet-associated CD154...

..This is the first time that single round in vivo biopanning has been used to select human antibodies as candidates for diagnostic imaging and for obtaining insight into targets displayed in atherosclerotic plaques...

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..These results suggest that administering autologous platelet-rich clots may be beneficial to the treatment of tendon injuries by inducing cell proliferation and promoting the synthesis of angiogenic factors during the healing process...

..It appears that FVIII's interaction with VWF and its intracellular transportation, storage, and secretion differ greatly depending on the cell type. The molecular basis for these differences now needs to be elucidated...

..In summary, these results show that abciximab-dependent thrombocytopenia can be delayed and potentially prothrombotic...

..The problems of using anti-integrin therapy are discussed in this article as are ways of improving its efficacity. Final thoughts provide ideas for a new generation of inhibitors...

..Substitute therapies are available including rFVIIa and the potential use of TPO analogues for FT. Stem cell or bone marrow transplanation is being used for severe diseases while gene therapy may be on the horizon...

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..Therefore, platelet-associated CD154 expression is increased in ITP and is able to drive the activation of autoreactive B lymphocytes in this disease...

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