Abstract：
:To understand the role of the factor X (fX) activation peptide (AP), a deletion mutagenesis approach was employed. Two single-chain, variant enzymes were generated in which 41 residues were deleted from the AP: fX (des-137-183) and fX(des-137-183;N191A), which lacks a carbohydrate moiety at Asn191 due to an alanine substitution. Deletion of the fX AP did not impact fXa catalytic activity. Activation of the variant zymogens, however, was altered. Neither mutant enzyme was activated by the fX coagulant protein from Russell's viper venom (RVV-X(1)). Activation by factor VIIa (fVIIa) and fVIIa in the presence of cofactor, lipidated tissue factor (TF), occurred at an accelerated rate for both variants as compared to wild-type fX (WTfX). Similar to fVII, the mutants auto-activated in a cofactor-independent manner, which was characterized by a lag period and accelerated dose-dependently by plasma fXa (kcat/Km, 0.046 +/- 0.004 micro M(-1) s(-1)). Both mutants were also found to be activated by fVIIa (0.31 +/- 0.03 micro M(-1) s(-1)), fIXa (0.30 +/- 0.03 micro M(-1) s(-1)), and thrombin (0.00078 +/- 0.00015 micro M(-1) s(-1)). In all cases, the rate of activation was faster for fX(des-137-183;N191A) as compared to fX(des-137-183). We propose that the fX AP and Asn191 carbohydrate serve primarily as negative autoregulation mechanisms to prevent spurious activation of fX and secondarily in cofactor dependence and activator specificity.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Rudolph AE,Mullane MP,Porche-Sorbet R,Daust HA,Miletich JPkeywords:
subject
Has Abstractpub_date
2002-11-01 00:00:00pages
756-62issue
5eissn
0340-6245issn
2567-689Xpii
02110756journal_volume
88pub_type
杂志文章abstract：:Coumarin oral anticoagulant drugs have proven to be effective for the prevention of thromboembolic events. World-wide, warfarin is the most prescribed drug. In Europe, acenocoumarol and phenprocoumon are also administered. Yet it has been proven that variant alleles of the VKORC1 and CYP2C9 genotypes influence the pha...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：2008-12-01 00:00:00
abstract：:The endothelial protein C receptor (EPCR) is expressed by trophoblast cells. Mid-gestation pregnancy loss is described in animals with a haemochorial placenta lacking EPCR. The A6936G allele of the EPCR gene (PROCR) may be associated with lower EPCR densities on trophoblasts, but data are lacking for its effect on the...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH-09-04-0224
更新日期：2009-10-01 00:00:00
abstract：:Von Willebrand disease (VWD) is the most common inherited bleeding disorder and is mainly caused by dominant-negative mutations in the multimeric protein von Willebrand factor (VWF). These mutations may either result in quantitative or qualitative defects in VWF. VWF is an endothelial protein that is secreted to the c...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/s-0040-1715442
更新日期：2020-11-01 00:00:00
abstract：:Fibrin D-Dimer (D-Di), prothrombin activation fragment (F 1+2) and thrombin-antithrombin III complexes (TAT) were measured using ELISA procedures in the plasma of patients with an acute deep venous thrombosis (DVT), at presentation and on days 2, 6 and 10 after initiation of heparin treatment. Patients were randomly a...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1993-12-20 00:00:00
abstract：:Thromboembolic complications have been attributed to the use of radiographic contrast media (CM) during interventional procedures for arterial revascularization. However, due to the low frequency of adverse events, comparisons between different CM have been difficult to perform, although it has been suggested that ion...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-03-01 00:00:00
abstract：:Evaluation of factor F(V)III replacement in patients with haemophilia A undergoing surgery is critical for FVIII concentrates, yet large scale, multi-center prospective studies, particularly using continuous infusion, are generally lacking for new products. This study evaluated efficacy and safety of a newly developed...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章,多中心研究
doi：
更新日期：2008-08-01 00:00:00
abstract：:Five expert laboratories have participated in a cross-laboratory study to co-evaluate and compare three commercial Factor VIII/von Willebrand factor (VWF) concentrates. A total of nine factor concentrate lots were evaluated, comprising AHF (High Purity) (AHF HP; x3), Biostate (x3) and Humate/Haemate (x3). All laborato...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2002-03-01 00:00:00
abstract：:Underlying disorders of the coagulation system such as inhibitor deficiencies or decreased fibrinolysis are common in patients suffering from venous thrombosis. They may lead to the necessity of a lifelong prophylaxis. Prompt diagnosis is obviously to the patients benefit. We investigated 22 patients suffering from ve...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
abstract：:We compared the antithrombotic and hemorrhagic effects of naturally existing human urinary soluble thrombomodulin (MR-33) with those of low molecular weight heparin (LMW-heparin) in rats. In in vitro experiments, MR-33 prolonged APTT in a dose-dependent fashion; its effect in this respect was as potent as that of LMW-...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-04-01 00:00:00
abstract：:Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication of allogeneic hematopoietic cell transplantation (HCT). We hypothesized that pretransplant genetic susceptibility is evident in adult TA-TMA and further investigated the association of TMA-associated variants with clinical out...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/s-0040-1702225
更新日期：2020-04-01 00:00:00
abstract：:D-dimer, a marker of fibrin turnover, exhibits many interesting properties as a biological marker of thrombosis. Some of the properties of D-dimer might also be used to provide additional information about patients with heart failure. In this study, we evaluate the prognostic information acquired from D-dimer concerni...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH04-05-0278
更新日期：2004-12-01 00:00:00
abstract：:Interactions between endothelial cell adhesion molecules and their beta2 integrin adhesive receptors on leukocytes are thought to play a role in the pathogenesis of inflammatory diseases and probably vasculitis. We describe a case in whom leukocytoclastic vasculitis was associated to a monoclonal immunoglobulin G2 kap...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-09-01 00:00:00
abstract：:We studied the HR2 haplotype of the factor V gene in a case-control study for venous thrombosis including 474 patients with a first deep-vein thrombosis and 474 age- and sex-matched healthy controls (Leiden Thrombophilia Study, LETS). We investigated both the original His1299Arg (A4070G) polymorphism and the Met385Thr...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2000-04-01 00:00:00
abstract：:The GAS6/ProS-TAM system is composed of two vitamin K-dependent ligands (GAS6 and protein S) and their three protein tyrosine kinase receptors TYRO3, AXL and MERTK, known as the TAM receptors. The system plays a prominent role in conditions of injury, inflammation and repair. In murine models of atherosclerotic plaque...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH10-10-0630
更新日期：2011-05-01 00:00:00
abstract：:Platelet activation plays a pivotal role in physiological hemostasis and pathological thrombosis causing heart attack and stroke. Previous studies conclude that simultaneous activation of Gi and G12/13 signaling pathways is sufficient to cause platelet aggregation. However, using Gq knockout mice and Gq-specific inhib...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/s-0040-1714745
更新日期：2020-11-01 00:00:00
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journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH15-01-0051
更新日期：2015-11-25 00:00:00
abstract：:Urokinase plasminogen activator (uPA) system regulates extracellular matrix remodelling by activating ubiquitous protease plasmin in many important physiological processes. The system components include uPA, plasminogen activator inhibitors (PAIs) and uPA receptor (uPAR). Besides its role in physiological processes, u...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-0038-1675399
更新日期：2018-12-01 00:00:00
abstract：:Previous studies have shown an association between serum C-reactive protein (CRP) and cardiovascular disease (CVD) risk. The roles of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha) are less well established. The aim of the present study was to analyze the associations of CRP, IL-6 and TNFalpha with in...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH05-08-0571
更新日期：2006-03-01 00:00:00
abstract：:Antiphospholipid antibody (aPL) is a hallmark of antiphospholipid syndrome (APS), characterized by thrombosis and recurrent fetal loss. We developed a novel ELISA system to detect complement-fixing ability of anticardiolipin antibody (aCL), and evaluated its clinical usefulness through studying the prevalence of the a...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2000-05-01 00:00:00
abstract：:We report here on a patient whose abnormal fibrin clot was detected via the measurement of clot rigidity with a simple buoyant inner cylinder elastometer. The patient's clinical coagulation studies were all within normal limits except for prolonged thrombin and reptilase clotting times and high level of fibrin split p...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1979-10-31 00:00:00
abstract：:Plasminogen activator inhibitor type-1 (PAI-1) is a physiologic modulator of the fibrinolytic system. We have shown previously that PAI-1 biosynthesis in cultured cells depends on several factors in serum. Because platelets are richly endowed with specific growth factors and because the release reaction is an integral...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
abstract：:Sulodexide, a highly purified glycosaminoglycan, was investigated for treatment of venous leg ulcers. Patients (n = 235) undergoing local treatment including wound care and compression bandaging, were randomised to receive either sulodexide or matching placebo for three months. Primary study endpoint was complete ulce...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：
更新日期：2002-06-01 00:00:00
abstract：:It was found that the effect of heparin on the amidase activity of urokinase (E C 3.4.21.31), plasmin (E C 3.4.21.7) and trypsin (E C 3.4.21.4) depended on the substrate used. No effect of heparin on the amidase activity of urokinase and trypsin was observed when Pyro Glu-Gly-Arg-p-nitroanilide (S-2444) and alpha-N-ac...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1983-06-28 00:00:00
abstract：:Normal adults have very few circulating endothelial cells (CECs) in their blood, but increased levels have been shown in association with conditions associated with endothelial damage such as myocardial infarction and stroke. As atrial fibrillation (AF) is associated with a hypercoagulable state and abnormalities of p...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH05-02-0093
更新日期：2005-10-01 00:00:00
abstract：:Although intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) play a relevant role in atherosclerosis, little is known about the prognostic impact of their soluble forms (s) in patients with peripheral arterial disease (PAD). The aim of this prospective study was to verify whether ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH04-07-0440
更新日期：2005-03-01 00:00:00
abstract：:Positively charged macromolecule, polylysine (mol. wt. 15,000; 23,000; 180,000) could induce the platelet aggregation in low concentration but high concentration was required in the case of neutral macromolecule, dextran (mol. wt. 40,000; 250,000; 2,000,000). The larger molecules of polylysine and dextran were more ef...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1978-08-31 00:00:00
abstract：:It is known that the fibrinolysis inhibitors in the human placenta are proteins which, in vitro, block urokinase plasminogen activation and are for this reason called urokinase inhibitors. In the present study it was found, for the first time, that a slow-molecular urokinase inhibitor also occurs in the human placenta...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1980-02-29 00:00:00
abstract：:Erythropoietin has shown to be effective in the correction of the hemostatic defect present in uremic patients. We have investigated the possible effect of recombinant human erythropoietin (rHuEPO) on the signaling processes occurring in platelets. Platelet suspensions were obtained from hemodialyzed patients before a...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1999-10-01 00:00:00
abstract：:Prasugrel, through its active metabolite, reduces atherothrombosis and its clinical manifestations by inhibiting platelet activation and aggregation. Platelets also contribute to inflammation through interaction with different classes of leukocytes. We investigated whether the inhibitory effect of prasugrel on platele...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH11-12-0867
更新日期：2012-06-01 00:00:00
abstract：:Tissue thromboplastin apoprotein was partially purified from human brain. The apoprotein was recombined with mixed phospholipids to yield active thromboplastin. The recombined thromboplastin induced proteolytic activation of isolated human factor IX in the presence of factor VII and Ca2+. The clotting times of various...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1982-08-24 00:00:00
