Abstract：
:Plasminogen activator inhibitor-1 (PAI-1) is a unique member of the serpin family, as it spontaneously converts into a latent conformation. However, the exact mechanism of this conversion is not known. Previous studies reported that neutralizing monoclonal antibodies as well as reversal or removal of charges on the s3C-s4C turn results in a destabilization of PAI-1 leading to an accelerated conversion to its latent form. In this study the effect of the reversal or removal of charges in this "gate region" (R186E/R187E, H190E/K191E, H190L/K191L and R356E) on a stable PAI-1-variant (PAI-1-stab) was investigated. Whereas PAI-1-stab has a half-life of 150+/-66 h, PAI-1-stab-R186E-R187E, PAI-1-stab-H190E-K191E, PAI-1-stab-H190L-K191L and PAI-1-stab-R356E have a strongly decreased half-life (p< 0.005 versus PAI-1-stab) of 175+/-48 min, 75+/-34 min, 68+/-38 min and 79+/-16 min, respectively. Wild-type PAI-1 (wtPAI-1) had a half-life of 55+/-19 min. These data indicate that the stabilization induced by the mutated residues in PAI-1-stab is counteracted by the additional mutations, resulting in half-lives similar to that of wtPAI-1, thereby suggesting that the stabilizing and destabilizing forces act mainly independently in these mutants. Extrapolation of these data to other (stable) serpins leads to the hypothesis that the s3C-s4C turn and the distal hinge region of the reactive site loop plays a role for the stability of serpins in general.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Vleugels N,Leys J,Knockaert I,Declerck PJkeywords:
subject
Has Abstractpub_date
2000-11-01 00:00:00pages
871-5issue
5eissn
0340-6245issn
2567-689Xpii
00110871journal_volume
84pub_type
杂志文章abstract：:The content of free-catecholamines in blood platelets is much higher than in plasma and platelet catecholamines must be taken up from plasma, since platelets lack the enzymes for catecholamine synthesis. There is some evidence that platelet catecholamine content under certain circumstances may be an integrated measure...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1988-10-31 00:00:00
abstract：:The tail bleeding time (BT) in rats definitely varies according to the method applied. Of the various variables that may influence BT, we have evaluated the position (horizontal or vertical) of the tail, the environment (air or saline), the temperature (4 degrees, 23 degrees or 37 degrees C) and the type of anaesthesi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1982-08-24 00:00:00
abstract：:Previous studies have demonstrated that cell-permeable cytoplasmic tail (CT) alpha(II)beta peptides can modulate the activation of alpha(IIb)b(3). As alpha(V) CT contains an alpha(II)beta homologous region, a series of cell-permeable alpha(V) and alpha(IIb) peptides were generated to determine if alpha(V) CT can modul...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH07-08-0498
更新日期：2008-01-01 00:00:00
abstract：:Recombinant human activated protein C (APC), which has both anticoagulant and anti-inflammatory properties, improves survival of patients with severe sepsis. This beneficial effect is especially apparent in patients with pneumococcal pneumonia. Earlier treatment with APC in sepsis has been associated with a better the...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH11-06-0438
更新日期：2011-12-01 00:00:00
abstract：:Mouse C127 epithelioid cells were genetically engineered to produce biologically active gamma-carboxylated human protein S. A full length human protein S cDNA was cloned into a bovine papilloma virus (BPV) based shuttle vector under the transcriptional control of the Moloney murine sarcoma virus enhancer and the mouse...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1992-05-04 00:00:00
abstract：:The fibrin-specificity and procoagulant effects of recombinant staphylokinase (Sak42D) were compared with those of recombinant tissue-type plasminogen activator (rt-PA) in patients with acute myocardial infarction. Plasma samples were obtained at baseline and at 25 and 90 min, from 24 patients who were randomly assign...
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：1996-12-01 00:00:00
abstract：:Vitamin K-dependent proteins are currently purified from pooled human plasma or produced in mammalian cell culture systems by recombinant DNA technology. Transgenic animals may provide an additional expression system for the production of these therapeutic proteins. Mice have been used to test hybrid genes which direc...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：1997-07-01 00:00:00
abstract：:Peripheral vascular disease (PVD) is an indicator of diffuse atherosclerosis and is associated with a greatly increased incidence of coronary heart and cerebrovascular disease. Although several studies have assessed whether in vivo platelet activation takes place in patients with PVD, no data are available comparing d...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-12-01 00:00:00
abstract：:Most of the knowledge acquired on platelet function and biochemistry has been obtained from platelets prepared from blood anticoagulated with sodium citrate. Using washed platelets from human blood (PNB) to which no anticoagulants were added, we report on responses not observed with platelets prepared from citrate-ant...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1986-10-21 00:00:00
abstract：:The in vitro effect of nifedipine, a calcium channel blocker of the dihydropyridine (DHP) type, on platelet aggregation was reinvestigated considering especially the capability of platelets to form endogenous nitric oxide (NO). We studied the dose-dependent antiaggregatory property of nifedipine in porcine platelet ri...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1994-08-01 00:00:00
abstract：:The effects of argatroban, a direct thrombin inhibitor, on the International Normalized Ratio (INR), activated partial thromboplastin time (aPTT) and functional factor X during warfarin co-administration were established to provide means to interpret INRs during argatroban/warfarin co-therapy. Twenty-four subjects rec...
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：2001-03-01 00:00:00
abstract：:We have developed a simple assay that measures the circulating activated protein C (APC) in plasma. The assay requires collection of duplicate blood samples, one in citrate plus heparin and the other in citrate plus inhibitors of the enzyme. In the heparin tube, APC reacts completely and irreversibly with its major pl...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1996-01-01 00:00:00
abstract：:Myocardial infarction results from a platelet-rich occlusive coronary thrombus. Platelet membrane glycoprotein IIb/IIIa plays an important role in platelet adhesion and aggregation. Two polymorphisms of the gene encoding the IIIa subunit. PLA1 and PLA2, have been identified. We investigated the frequency of these poly...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章
doi：
更新日期：1998-08-01 00:00:00
abstract：:Venous thromboembolic (VTE) complications in children and adolescents with acute lymphoblastic leukaemia (ALL) and T or B cell lymphoblastic lymphoma (T/B cell LL) can result not only in life-threatening acute complications but also contribute to significant long-term sequelae. The PREVAPIX-ALL study is an open-label ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1055/s-0039-1679938
更新日期：2019-05-01 00:00:00
abstract：:Congenitally abnormal fibrinogen Osaka III with the replacement of gamma Arg-275 by His was found in a 38-year-old female with no bleeding or thrombotic tendency. Release of fibrinopeptide(s) by thrombin or reptilase was normal, but her thrombin or reptilase time in the absence of calcium was markedly prolonged and th...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1992-11-10 00:00:00
abstract：:Antithrombin (AT) is a protein of the serpin superfamily involved in regulation of the proteolytic activity of the serine proteases of the coagulation system. AT is known to exhibit anti-inflammatory and cardioprotective properties when it binds to heparan sulfate proteoglycans (HSPGs) on vascular cells. AMP-activated...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH14-04-0360
更新日期：2015-02-01 00:00:00
abstract：:The effects of etamsylate on human platelet aggregation and ATP release as well as on the arachidonate metabolism by the platelet have been studied. Etamsylate enhanced these platelet functions induced by arachidonic acid (AA), thromboxane A2, collagen and calcium ionophore A23187 but not those induced by ADP and epin...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1982-12-27 00:00:00
abstract：:Activated blood coagulation factor XIII has an important role in the final stage of the clotting cascade by the covalent crosslinking of alpha- and gamma-fibrin chains. We have recently shown that a functional polymorphism in exon 2. codon 34 of the FXIII A-subunit gene is protective against myocardial infarction. To ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1999-04-01 00:00:00
abstract：:The Bernard-Soulier syndrome (BSS) is characterized by thrombocytopenia with giant platelets, a prolonged bleeding time with defective platelet adhesion to the subendothelium related to a defect in platelet membrane glycoprotein Ib (GPIb) and a decreased prothrombin consumption. The mechanism of the latter abnormality...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-02-01 00:00:00
abstract：:It was the study objective to determine whether glycaemic control affects the extent of platelet inhibition by thienopyridines as assessed by vasodilator-stimulated phosphoprotein flow cytometry (VASP-FCT) in patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) during acute coronary...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH11-12-0876
更新日期：2012-08-01 00:00:00
abstract：:In the past decade understanding of the role of the Rho GTPases RhoA, Rac1 and Cdc42 has been developed from regulatory proteins that regulate specific actin cytoskeletal structures - stress fibers, lamellipodia and filopodia - to complex integrators of cytoskeletal structures that can exert multiple functions dependi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH09-06-0403
更新日期：2010-01-01 00:00:00
abstract：:We have recently demonstrated that the proinflammatory cytokine, interleukin-6 (IL-6), could upregulate the production of protein S in the human hepatoma cell line, HepG-2, but not in endothelial cells. In this study, we have demonstrated that the combination of exogenous IL-6 and soluble IL-6 receptor (sIL-6R) could ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-05-01 00:00:00
abstract：:The still living members of the original bleeder family on the Aland Islands described by von Willebrand in 1926 have been reinvestigated by using modern laboratory techniques for the measurement of the Factor VIII complex and with regard to platelet aggregation. The low level of F VIII : C activity demonstrated in 19...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1981-02-23 00:00:00
abstract：:Hyperglycemia-induced mitochondrial overproduction of reactive oxygen species leads to the activation of different biochemical pathways involved in endothelial damage of the diabetic retina. Tenilsetam [(+/-)-3-(2-thienyl)-2-piperazinone] is a dicarbonyl scavenger in the millimolar range and a transition metal ion che...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2006-04-01 00:00:00
abstract：:Three single nucleotide polymorphisms (-603A/G, -1322C/T, -1812C/T) and one deletion/insertion polymorphism (-1208D/I) are present in the tissue factor (TF) gene promoter sequence. These polymorphisms are in complete linkage disequilibrium, determining two haplotypes with almost equal frequency. The -603A/-1208D/-1322...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH03-09-0566
更新日期：2004-02-01 00:00:00
abstract：INTRODUCTION: Bleeds such as intra-ventricular (IVH) and pulmonary haemorrhage (PH) are life-threatening events in extremely low birth weight (ELBW) infants. Serial coagulation monitoring by measuring the international normalized ratio (INR) with small volume samples might facilitate early diagnosis and possibly preven...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/s-0038-1655744
更新日期：2018-07-01 00:00:00
abstract：:We examined the ability of unfractionated heparin to modulate the procoagulant activities of stimulated endothelial cells (EC). Confluent human venous umbilical EC were incubated with heparin before or after stimulation, then rinsed extensively to eliminate any heparin in the solution. EC, stimulated for 4 h with endo...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1996-01-01 00:00:00
abstract：:Tissue factor (TF) plays a pivotal role in thrombus formation and atherogenesis in acute coronary syndrome. Tissue factor pathway inhibitor (TFPI) is a specific physiological inhibitor of TF/FVIIa complex that regulates TF-induced coagulation. Adiponectin (Adp) is an adipocyte-specific adipocytokine with anti-atheroge...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2008-08-01 00:00:00
abstract：:Heparin-coating improves the biocompatibility of blood contacting artificial surfaces. This led us to investigate the impact of heparin-coating (Carmeda AB, Stockholm) of polymetylmetacrylate on the expression of monocyte tissue factor procoagulant activity (TF-PCA) by surface adhesion. Also, the anticoagulant effect ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-02-01 00:00:00
abstract：:The aim of this study was to evaluate the existence of an additive effect between standard heparin and dDAVP in the enhancement of endogenous fibrinolysis. Eight healthy volunteers were studied in a randomized double blind placebo controlled cross-over trial. The volunteers were treated i.v. with dDAVP, 0.4 micrograms...
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：1989-06-30 00:00:00
