The Experts below are selected from a list of 246 Experts worldwide ranked by ideXlab platform
Han-mou Tsai - One of the best experts on this subject based on the ideXlab platform.
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Von Willebrand Factor and Von Willebrand Factor-cleaving metalloprotease activity in Escherichia coli O157:H7-associated hemolytic uremic syndrome.
Pediatric Research, 2001Co-Authors: Han-mou Tsai, Wayne L Chandler, Ravindra Sarode, Robert Hoffman, Srdjan Jelacic, Rebecca L. Habeeb, Sandra L. Watkins, Craig S. Wong, Glyn D Williams, Phillip I. TarrAbstract:Hemolytic uremic syndrome (HUS) usually occurs after infection with Shiga toxin-producing bacteria. Thrombotic thrombocytopenic purpura, a disorder with similar clinical manifestations, is associated with deficient activity of a circulating metalloprotease that cleaves Von Willebrand Factor at the Tyr842-Met843 peptide bond in a shear stress-dependent manner. We analyzed Von Willebrand Factor-cleaving metalloprotease activity and the status of Von Willebrand Factor in 16 children who developed HUS after Escherichia coli O157:H7 infection and in 29 infected children who did not develop this complication. Von Willebrand Factor-cleaving metalloprotease activity was normal in all subjects, but Von Willebrand Factor size was decreased in the plasma of each of 16 patients with HUS. The decrease in circulating Von Willebrand Factor size correlated with the severity of thrombocytopenia and was proportional to an increase in Von Willebrand Factor proteolytic fragments in plasma. Immunohistochemical studies of the kidneys in four additional patients who died of HUS demonstrated glomerular thrombi in three patients, and arterial and arteriolar thrombi in one patient. The glomerular thrombi contained fibrin but little or no Von Willebrand Factor. A decrease in large Von Willebrand Factor multimers, presumably caused by enhanced proteolysis from abnormal shear stress in the microcirculation, is common in HUS.
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antibody inhibitors to Von Willebrand Factor metalloproteinase and increased binding of Von Willebrand Factor to platelets in ticlopidine associated thrombotic thrombocytopenic purpura
Annals of Internal Medicine, 2000Co-Authors: Han-mou Tsai, Ravindra Sarode, Lawrence Rice, Thomas W Chow, Joel L MoakeAbstract:In patients who developed ticlopidine-associated thrombotic thrombocytopenic purpura (TTP), autoantibodies to Von Willebrand Factor metalloproteinase were formed; this led to the same type of Von W...
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antibodies to Von Willebrand Factor cleaving protease in acute thrombotic thrombocytopenic purpura
The New England Journal of Medicine, 1998Co-Authors: Han-mou Tsai, Eric Chunyet LianAbstract:Background Thrombotic thrombocytopenic purpura is a potentially fatal disease characterized by widespread platelet thrombi in the microcirculation. In the normal circulation, Von Willebrand Factor is cleaved by a plasma protease. We explored the hypothesis that a deficiency of this protease predisposes patients with thrombotic thrombocytopenic purpura to platelet thrombosis. Methods We studied the activity of Von Willebrand Factor–cleaving protease and sought inhibitors of this protease in plasma from patients with acute thrombotic thrombocytopenic purpura, patients with other diseases, and normal control subjects. We also investigated the effect of shear stress on the ristocetin coFactor activity of purified Von Willebrand Factor in the cryosupernatant fraction of the plasma samples. Results Thirty-nine samples of plasma from 37 patients with acute thrombotic thrombocytopenic purpura had severe deficiency of Von Willebrand Factor–cleaving protease. No deficiency was detected in 16 samples of plasma from ...
U Mittler - One of the best experts on this subject based on the ideXlab platform.
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Von Willebrand Factor cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome
The New England Journal of Medicine, 1998Co-Authors: M Furlan, Rodolfo Robles, Miriam Galbusera, Giuseppe Remuzzi, Paul A Kyrle, Brigitte Brenner, M Krause, I Scharrer, V Aumann, U MittlerAbstract:Background Thrombotic thrombocytopenic purpura and the hemolytic–uremic syndrome are severe microvascular disorders of platelet clumping with similar signs and symptoms. Unusually large multimers of Von Willebrand Factor, capable of agglutinating circulating platelets under high shear stress, occur in the two conditions. We investigated the prevalence of Von Willebrand Factor–cleaving protease deficiency in patients with familial and nonfamilial forms of these disorders. Methods Plasma samples were obtained from 53 patients with thrombotic thrombocytopenic purpura or hemolytic–uremic syndrome. Von Willebrand Factor–cleaving protease was assayed in diluted plasma samples with purified normal Von Willebrand Factor as the substrate. The extent of the degradation of Von Willebrand Factor was assessed by electrophoresis in sodium dodecyl sulfate–agarose gels and immunoblotting. To determine whether an inhibitor of Von Willebrand Factor–cleaving protease was present, we measured the protease activity in normal ...
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Von Willebrand Factor–Cleaving Protease in Thrombotic Thrombocytopenic Purpura and the Hemolytic–Uremic Syndrome
The New England Journal of Medicine, 1998Co-Authors: Miha Furlan, Rodolfo Robles, Miriam Galbusera, Giuseppe Remuzzi, Paul A Kyrle, Brigitte Brenner, M Krause, I Scharrer, V Aumann, U MittlerAbstract:Background Thrombotic thrombocytopenic purpura and the hemolytic–uremic syndrome are severe microvascular disorders of platelet clumping with similar signs and symptoms. Unusually large multimers of Von Willebrand Factor, capable of agglutinating circulating platelets under high shear stress, occur in the two conditions. We investigated the prevalence of Von Willebrand Factor–cleaving protease deficiency in patients with familial and nonfamilial forms of these disorders. Methods Plasma samples were obtained from 53 patients with thrombotic thrombocytopenic purpura or hemolytic–uremic syndrome. Von Willebrand Factor–cleaving protease was assayed in diluted plasma samples with purified normal Von Willebrand Factor as the substrate. The extent of the degradation of Von Willebrand Factor was assessed by electrophoresis in sodium dodecyl sulfate–agarose gels and immunoblotting. To determine whether an inhibitor of Von Willebrand Factor–cleaving protease was present, we measured the protease activity in normal ...
Francesco Rodeghiero - One of the best experts on this subject based on the ideXlab platform.
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Recommended Abbreviations for Von Willebrand Factor and Its Activities On behalf of the Von Willebrand Factor Subcommittee of the Scientific and tandardization Committee of the ISTH
Thrombosis and Haemostasis, 2020Co-Authors: Claudine Mazurier, Francesco RodeghieroAbstract:Recommended Abbreviations for Von Willebrand Factor and Its Activities On behalf of the Von Willebrand Factor Subcommittee of the Scientific and tandardization Committee of the ISTH -
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RECOMMENDED ABBREVIATIONS FOR Von Willebrand Factor AND ITS ACTIVITIES On behalf of the Von Willebrand Factor Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis
Thrombosis and Haemostasis, 2017Co-Authors: Claudine Mazurier, Francesco RodeghieroAbstract:Previous official recommendations concerning the abbreviations for Von Willebrand Factor (and Factor VIII) are 15 years old and were limited to "vWf" for the protein and "vWf:Ag" for the antigen (1). Nowadays, the various properties of Von Willebrand Factor (ristocetin coFactor activity and capacity to bind to either collagen or Factor VIII) are better defined and may warrant specific abbreviations. Furthermore, the protein synthesized by the Von Willebrand Factor gene is now abbreviated as pre-pro-VWF (2). Accordingly, the subcommittee on Von Willebrand Factor of the Scientific and Standardization Committee of the ISTH has recommended new abbreviations for Von Willebrand Factor antigen and its various activities, currently measured by immunologic or functional assays (Table I). It is hoped that a uniform application of the abbreviations recommended here will improve communication among scientists and clinicians, especially for those who are less familiar with the field.
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Pregnancy and delivery in women with Von Willebrand's disease and different Von Willebrand Factor mutations.
Haematologica, 2009Co-Authors: Giancarlo Castaman, Alberto Tosetto, Francesco RodeghieroAbstract:Background Pregnancy in Von Willebrand’s disease may carry a significant risk of bleeding. Information on changes in Factor VIII and Von Willebrand Factor and pregnancy outcome in relation to Von Willebrand Factor gene mutations are very scanty. Design and Methods We examined biological response to desmopressin, changes in Factor VIII and Von Willebrand Factor and pregnancy outcome in a cohort of 23 women with Von Willebrand’s disease characterized at molecular level and prospectively followed during 2000–2007. Results Thirty-one pregnancies occurred during the study period. Remarkably, similar changes of Factor VIII and Von Willebrand Factor were observed after desmopressin and during pregnancy in nine women with R854Q, R1374H, V1665E, V1822G and C2362F mutations. Women with Von Willebrand’s disease and R1205H and C1130F mutations (17 pregnancies in 12 women) had only a slight increase of Factor VIII and Von Willebrand Factor during pregnancy while their response to desmopressin was marked but short-lived. For these women, two to three desmopressin administrations within the first 48 hours were sufficient to successfully manage vaginal delivery. Two women with recessive Von Willebrand’s disease due to compound heterozygosity for different gene mutations had a spontaneous, major increase in Factor VIII while Von Willebrand Factor remained severely reduced. Desmopressin increased Factor VIII and was clinically useful in the first case, while a Factor VIII/Von Willebrand Factor concentrate was required in the second patient not responsive to the compound. Factor VIII/Von Willebrand Factor concentrate was also required for two women with type 2 A Von Willebrand’s disease with V1665E mutations who had no Von Willebrand Factor activity change during pregnancy. In one of them, delayed bleeding occurred 15 days later requiring treatment with Factor VIII/Von Willebrand Factor concentrate. No miscarriages or stillbirths occurred. Conclusions Close follow-up and detailed guidelines for the management of parturition have produced a very low rate of immediate and late bleeding complications in this setting. Desmopressin was effective and safe in preventing significant bleeding at delivery in most of these patients.
Eric Chunyet Lian - One of the best experts on this subject based on the ideXlab platform.
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antibodies to Von Willebrand Factor cleaving protease in acute thrombotic thrombocytopenic purpura
The New England Journal of Medicine, 1998Co-Authors: Han-mou Tsai, Eric Chunyet LianAbstract:Background Thrombotic thrombocytopenic purpura is a potentially fatal disease characterized by widespread platelet thrombi in the microcirculation. In the normal circulation, Von Willebrand Factor is cleaved by a plasma protease. We explored the hypothesis that a deficiency of this protease predisposes patients with thrombotic thrombocytopenic purpura to platelet thrombosis. Methods We studied the activity of Von Willebrand Factor–cleaving protease and sought inhibitors of this protease in plasma from patients with acute thrombotic thrombocytopenic purpura, patients with other diseases, and normal control subjects. We also investigated the effect of shear stress on the ristocetin coFactor activity of purified Von Willebrand Factor in the cryosupernatant fraction of the plasma samples. Results Thirty-nine samples of plasma from 37 patients with acute thrombotic thrombocytopenic purpura had severe deficiency of Von Willebrand Factor–cleaving protease. No deficiency was detected in 16 samples of plasma from ...
J. E. Sadler - One of the best experts on this subject based on the ideXlab platform.
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Von Willebrand Factor.
Journal of Biological Chemistry, 1991Co-Authors: J. E. SadlerAbstract:Von Willebrand Factor has an important function in the maintenance of haemostasis by promoting platelet-vessel wall interactions at sites of vascular injury. The molecule is a multimeric plasma glycoprotein synthesized by endothelial cells and megakaryotes and it serves as both a carrier for Factor VIII and as a mediator of initial platelet adhesion to the subendothelium. Multimerization provides a greater density of platelet-binding sites. Von Willebrand Factor interacts with two known platelet receptors, the membrane glycoprotein complexes Ib/IX and IIbIIIa (integrin α IIb β 3), as well as with collagen and heparin. IIbIIIa recognition involves a single RGD motif and Ib/IX recognition is induced by the viper venom protein botrocetin. In plasma, Von Willebrand Factor circulates as multimers ranging in size from dimers of about 500 kDa to multimers of 20,000 kDa, at a concentration of 5–10 μg/ml. The molecule is synthesized as a pre-propolypeptide, which is cleaved and modified. Its cysteine residues are all involved in inter- and intra-chain disulphide bonds and are clustered at the NH 2 - and COOH-termini of the molecule. Von Willebrand Factor and Factor VIII can be isolated from plasma by cryoprecipitation and agarose gel filtration. It is possible to separate Factor VIII from Von Willebrand Factor by gel filtration in high ionic strength buffers.
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human Von Willebrand Factor gene and pseudogene structural analysis and differentiation by polymerase chain reaction
Biochemistry, 1991Co-Authors: D. J. Mancuso, Elodee A. Tuley, Lisa A. Westfield, J. M. Sorace, T L Lestermancuso, M Le M Beau, J. E. SadlerAbstract:Structural analysis of the Von Willebrand Factor gene located on chromosome 12 is complicated by the presence of a partial unprocessed pseudogene on chromosome 22q11-13. The structures of the Von Willebrand Factor pseudogene and corresponding segment of the gene were determined, and methods were developed for the rapid differentiation of Von Willebrand Factor gene and pseudogene sequences. The pseudogene is 21-29 kilobases in length and corresponds to 12 exons (exons 23-34) of the Von Willebrand Factor gene. Approximately 21 kilobases of the gene and pseudogene were sequenced, including the 5{prime} boundary of the pseudogene. The 3{prime} boundary of the pseudogene lies within an 8-kb region corresponding to intron 34 of the gene. The presence of splice site and nonsense mutations suggests that the pseudogene cannot yield functional transcripts. The pseudogene has diverged {approximately}3.1{percent} in nucleotide sequence from the gene. This suggests a recent evolutionary origin {approximately}19-29 million years ago, near the time of divergence of humans and apes from monkeys. Several repetitive sequences were identified, including 4 Alu, one Line-1, and several short simple sequence repeats. Several of these simple repeats differ in length between the gene and pseudogene and provide useful markers for distinguishing these loci. Sequence differences betweenmore » the gene and pseudogene were exploited to design oligonucleotide primers for use in the polymerase chain reaction to selectivity amplify sequences corresponding to exons 23-34 from either the Von Willebrand Factor gene or the pseudogene. This method is useful for the analysis of gene defects in patients with Von Willebrand disease, without interference from homologous sequences in the pseudogene.« less
