Abstract:
:Coumarin and homologous compounds are the most widely used anticoagulant drugs worldwide. They function as antagonists of vitamin K, an essential cofactor for the posttranslational gamma-glutamyl carboxylation of the so-called vitamin K-dependent proteins. As vitamin K hydroquinone is converted to vitamin K epoxide (VKO) in every carboxylation step, the epoxide has to be recycled to the reduced form by the vitamin K epoxide reductase complex (VKOR). Recently, a single coumarin-sensitive protein of the putative VKOR enzyme complex was identified in humans (vitamin K epoxide reductase complex subunit 1, VKORC1). Mutations in VKORC1 result in two different phenotypes: warfarin resistance (WR) and multiple coagulation factor deficiency type 2 (VKCFD2). Here,we report on the expression of site-directed VKORC1 mutants, addressing possible structural and functional roles of all seven cysteine residues (Cys16, Cys43, Cys51, Cys85, Cys96, Cys132, Cys135), the highly conserved residue Ser/Thr57, and Arg98, known to cause VKCFD2 in humans. Our results support the hypothesis that the C132-X-X-C135 motif in VKORC1 comprises part of the redox active site that catalyzes VKO reduction and also suggest a crucial role for the hydrophobic Thr-Tyr-Ala motif in coumarin binding. Furthermore, our results support the concept that different structural components of VKORC1 define the binding sites for vitamin K epoxide and coumarin.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Rost S,Fregin A,Hünerberg M,Bevans CG,Müller CR,Oldenburg Jdoi
10.1160/TH05-02-0082keywords:
subject
Has Abstractpub_date
2005-10-01 00:00:00pages
780-6issue
4eissn
0340-6245issn
2567-689Xpii
05100780journal_volume
94pub_type
杂志文章abstract::Increased plasma plasminogen activator inhibitor-1 (PAI-1) has been implicated in the development of vascular disease. In type 2 diabetes mellitus high PAI-1 levels are associated with increased plasma concentrations of free fatty acids (FFA) and triacylglycerol indicating an association or a causal relationship. To a...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1160/TH03-07-0457
更新日期:2003-09-01 00:00:00
abstract::The aim of the present study was to evaluate the relative performance of five screening methods for APC resistance caused by the factor V:Q506 mutation: the original method Coatest APC Resistance Chromogenix, a modified method using the same reagents but a predilution 1+4 of the plasma in a factor V deficient plasma f...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-11-01 00:00:00
abstract::Acid-treated human plasma is a competitive inhibitor of the hydrolysis of D-Val-Leu-Lys-Nan (S-2251) by plasmin. The rate of hydrolysis is decreased to 50% by 750 fold diluted acidified normal plasma and by 60 fold diluted acidified alpha 2-antiplasmin depleted plasma (alpha 2-antiplasmin concentration less than 2%). ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1982-12-27 00:00:00
abstract::In order to determine the molecular size of human F VIII as found in fresh plasma and as found in fresh-frozen plasma and in cryoprecipitate and to study the relationship of the factor-related properties, namely F VIII:C, F VIIR:Rcof and F VIIIR:Ag to F VIII, the factor's elution pattern on Sephacryl 1000 was investig...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1982-08-24 00:00:00
abstract::In vitro and in vivo effects of adrenaline (ADR) on platelet aggregation, on platelet factor 3 (PF3) availability and on platelet factor 4 (PF4) release were studied in man. Inhibitory action of an alpha-blocker, phentolamine (PHEN) was investigated in the same conditions. The threshold concentration (TC) of ADR induc...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1978-10-31 00:00:00
abstract::Thromboelastography (TEG) has been shown to be a valuable point-of-care device for the rapid diagnosis of various bleeding disorders. However, TEG has thus far not been used for the screening for von Willebrand disease (VWD). We evaluated the performance of a modified TEG assay for the laboratory screening of VWD. Thr...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH10-12-0782
更新日期:2011-06-01 00:00:00
abstract::This study examines the relationship between plasma Plasminogen Activator Inhibitor-1 (PAI-1) activity and the PAI-1 4G/5G polymorphism, and their association with the risk of myocardial infarction (MI). Furthermore, this study explores whether a high level of PAI-1 or whether the PAI-1 4G/5G polymorphism synergistica...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2003-06-01 00:00:00
abstract::Thrombotic complications are frequently associated with atherosclerosis. Lysophosphatidylcholine (LPC), a component accumulated in oxidatively modified LDL (ox-LDL), is known to play a crucial role in the initiation and progression of atherosclerotic vascular lesions. Since a vascular anticoagulant, tissue factor path...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::Endothelial cell protein C receptor (EPCR) enhances the generation of activated protein C (APC) by the thrombin-thrombomodulin complex. A soluble form of EPCR (sEPCR), which is generated by metalloprotease activity, is present in plasma. The distribution of sEPCR levels in healthy populations is bimodal. Previously, w...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH03-10-0657
更新日期:2004-05-01 00:00:00
abstract::Inhibition of adenylate cyclase in intact platelets by addition of compounds such as 2', 5' - dideoxyadenosine prevented the inhibition of platelet aggregation by PGE1 but did not affect the responses of platelets to aggregating agents in the absence of PGE1. This confirms that cyclic AMP mediates the effects of PGE1 ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1978-10-31 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::Pathogenic species of the genus Yersinia suppress and reorient the immune system to infect lymphatic tissues, inner organs and at times also the vasculature. For this purpose yersiniae employ a type III secretion system to translocate effector proteins (Yersinia outer proteins; Yops) into immune cells. Yops often exer...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:2007-09-01 00:00:00
abstract::We report genetic abnormalities of protein C gene in a male infant who developed neonatal purpura fulminans. DNA-sequence analysis of all exons in protein C gene in this family revealed two mutations. The first abnormality, derived from the mother, was a deletion of one of four consecutive G at nucleotide number 10758...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1993-10-18 00:00:00
abstract::The administration of recombinant activated factor VII (rFVIIa) by continuous infusion has provided a safe and convenient alternative to bolus injections in haemophiliacs with inhibitors, but it has only been reported in a single case with congenital factor VII (FVII) deficiency. The results of 12 consecutive surgical...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1160/TH05-05-0342
更新日期:2005-12-01 00:00:00
abstract::Factor Xa (fXa)-inhibitors are as effective and safer than vitamin-K-antagonists (VKA) in the treatment of venous thromboembolism (VTE). We previously classified the severity of clinical presentation and course of all major bleeding events from the EINSTEIN, AMPLIFY and HOKUSAI-VTE trials separately. The current aim w...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH16-12-0946
更新日期:2017-10-01 00:00:00
abstract:: ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0038-1657075
更新日期:1979-07-01 00:00:00
abstract::Thrombocytopenia and platelet dysfunction induced by extracorporeal blood circulation are thought to contribute to postsurgical bleeding complications in neonates undergoing cardiac surgery with cardiopulmonary bypass (CPB). In this study, we examined how changes in platelet function relate to changes in platelet coun...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0039-1700517
更新日期:2020-01-01 00:00:00
abstract::Platelet membrane glycoproteins (GP) IIb/IIa and rap1b, a 21 kDa GTP binding protein, associate with the triton-insoluble, activation-dependent platelet cytoskeleton with similar rates and divalent cation requirement. To examine the possibility that GPIIb/IIIa was required for rap1b association with the cytoskeleton, ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-04-01 00:00:00
abstract::When adenosine diphosphate (ADP) is added to hirudinized platelet-rich plasma (PRP) in which the level of platelet cAMP has been pharmacologically elevated, there is an initial rapid fall in the level of cAMP brought about by inhibition of adenylate cyclase. This may be followed by a subsequent activation of adenylate...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-08-01 00:00:00
abstract::Recurrent pregnancy loss (PL) is associated with maternal thrombophilia and prophylaxis with low molecular weight heparin (LMWH) can improve pregnancy outcome in this setting. The aim of this study was to investigate the modulation of systemic hemostatic parameters by enoxaparin in women with recurrent PL and to evalu...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH05-03-0212
更新日期:2005-11-01 00:00:00
abstract::Factor V Leiden is a procoagulant mutation associated with venous and arterial thrombosis and pregnancy complications. Its high prevalence of 5% in Caucasians suggests that there are evolutionary benefits as well. Carriers are indeed reported to have various advantageous phenotypes related to haemostasis, inflammation...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH13-02-0115
更新日期:2013-07-01 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::Human tissue kallikrein-related peptidases are a family of 15 secreted serine proteases, located at chromosome 19q13.4. Most of them have been reported to be potential biomarkers for several carcinomas and other diseases. Human tissue kallikrein-related peptidase 7 (KLK7) has been purified from human stratum corneum a...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2009-04-01 00:00:00
abstract::A group of 90 hemophiliacs who had been regularly treated with non virus-inactivated factor VIII or IX concentrates were studied in 1983. At that time 50 patients were HIV-1-antibody positive, 6 additional seroconversions occurred until 1985. 26 of the 50 patients seropositive in 1983 are currently asymptomatic. 4 pat...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1989-06-30 00:00:00
abstract::Platelet counts were evaluated in 714 patients with advanced non-small cell lung cancer (N-SCLC), small cell carcinoma of the lung (SCCL), and colon cancer entered to a clinical trial. Patients had not received prior chemotherapy. Platelet counts were not different in patients who had received radiation therapy prior ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1990-12-28 00:00:00
abstract::The haemostatic system and the use of heparin during cardiopulmonary bypass (CPB) have been studied extensively in adults but not in children. Results from adult trials cannot be extrapolated to children because of age-dependent physiologic differences in haemostasis. We studied 22 consecutive paediatric patients who ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-02-01 00:00:00
abstract::Coagulation factor XIII, a transglutaminase which stabilises blood clots by covalently cross-linking fibrin, is essential for normal haemostasis. FXIII deficiency results in a life-long bleeding disorder with added complications in wound healing and tissue repair. Sequence changes in the human FXIIIA gene, largely mis...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-06-01 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::The use of warfarin with a range INR of 2.0-3.0 is recommended in prevention of stroke for nonvalvular atrial fibrillation (AF) patients, in particular those older than 75 years. The risk of bleeding that is associated with this range of INR has led to evaluate lower ranges (low-dose or fixed minidose) in terms of ris...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,meta分析
doi:10.1160/TH03-08-0541
更新日期:2004-02-01 00:00:00
abstract:BACKGROUND: There have been no prior nationwide reports on the prevalence of hypertrophic cardiomyopathy (HCM) among patients suffering from atrial fibrillation (AF). It is also unclear how much stroke risk is attributable to HCM compared with other stroke risks in patients with AF. This study assessed the prevalence o...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0038-1676818
更新日期:2019-02-01 00:00:00