Abstract:
:Mammalian urokinase-type plasminogen activator (uPA) is produced as a stable single polypeptide chain zymogen and requires a distinct proteolytic cleavage to become an active, two-chain enzyme. In contrast, chicken uPA, both native and recombinant, is found predominantly as a two-chain, active enzyme even in the absence of plasmin, a physiological activator. Here we show that the proclivity to autoactivate is not a unique property of the chicken uPA catalytic domain but requires sequences distinct from and independent of the serine protease domain. Human/chicken chimeric uPA molecules and point mutants were used to determine the structural requirements for uPA autoactivation versus zymogen stability. The amino terminal fragment of chicken uPA engineered onto the human uPA molecule can induce the autoactivation of the human uPA. In fact, the first twenty residues of the chicken uPA are necessary and sufficient to induce the autoactivation of chicken and human uPA. These results indicate that sequence motifs, distal to the active site, control the substrate specificity and catalytic efficiency of uPA activity in autolytic activation.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Aimes RT,Regazzoni K,Quigley JPkeywords:
subject
Has Abstractpub_date
2003-02-01 00:00:00pages
382-92issue
2eissn
0340-6245issn
2567-689Xpii
03020382journal_volume
89pub_type
杂志文章abstract::Platelets are critically involved in atherosclerosis and acute thrombosis. The platelet phenotype shows a wide variability documented by the inherited difference of platelet reactivity, platelet volume and count and function of platelet surface receptors. Several candidate genes have been put into focus and investigat...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH13-02-0145
更新日期:2013-11-01 00:00:00
abstract::Matrix metalloproteinases (MMPs) play an important role in many biological and pathological processes including tissue remodeling, wound healing, inflammation, atherosclerosis, and cancer. Numerous publications have supported the concept that activated MMP-2 enhances agonist-induced platelet aggregation and activated ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-08-0541
更新日期:2005-02-01 00:00:00
abstract::Multiple clinical trials have proven that thrombolytic therapy is an effective treatment for acute myocardial infarction. Spontaneous intracranial hemorrhage (ICH) occurs in a small percentage of patients as a result of the treatment. The etiology of the ICH is unknown and there is currently no established experimenta...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract::Factor VIII procoagulant activity (F VIII:C) and factor VIII related antigen (F VIII R: Ag) were investigated in 35 patients with Argentine hemorrhagic fever. Since the results obtained in the three clinical forms of the disease were not significantly different, they were tabulated altogether. F VIII:C was low in earl...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1981-08-28 00:00:00
abstract::Antiphospholipid-protein antibodies (APA) include lupus-type anticoagulant (LA) and antibodies recognizing complexes of anionic phospholipids (e.g. cardiolipin) and proteins (e.g. prothrombin and beta2-glycoprotein I). The presence of APA is associated with an increased risk of both arterial and venous thrombosis. How...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-10-01 00:00:00
abstract::Shear stress has an established effect on mature endothelial cells, but less is known about how shear stress regulates endothelial progenitor cells (EPCs). In vitro expanded EPCs isolated from adult human blood represent a novel tool in regenerative vessel therapy. However, in vitro culturing may generate cells with u...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH09-12-0854
更新日期:2010-09-01 00:00:00
abstract::The most accepted therapy for DVT consists of anticoagulation with unfractionated heparin or low molecular weight heparin, followed by variable duration oral anticoagulation but thrombolytic therapy has been proposed in addition to standard anticoagulation. This paper reviews the literature on post thrombotic syndrome...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,meta分析
doi:
更新日期:2001-07-01 00:00:00
abstract::Echolucent carotid plaques are associated with higher risk for future ischemic cerebrovascular events (CVE) than echogenic plaques independent of the degree of stenosis. Elevated markers of thrombin generation are associated with atherosclerotic plaques and are increased in the acute and chronic phases of CVE. The pre...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH07-08-0493
更新日期:2008-03-01 00:00:00
abstract::The vast clinical research programme for the direct, oral factor Xa inhibitor rivaroxaban has generated a wealth of data since the first rivaroxaban approval in 2008 for the prevention of venous thromboembolism (VTE) in patients undergoing elective hip or knee replacement surgery. While rivaroxaban is widely used acro...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH16-06-0484
更新日期:2016-09-28 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::A technique has been developed to monitor the development of thrombin in freshly collected whole blood in the absence of anticoagulants. It is based on the centrifugal separation of the cellular components from subsamples of blood drawn from non-anticoagulated clotting whole blood which are diluted in buffer containin...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract::[This corrects the article DOI: 10.1160/TH14-06-0547.]. ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,已发布勘误
doi:10.1160/TH17040001
更新日期:2017-04-03 00:00:00
abstract::Platelet aggregation and adenine nucleotides in platelets have been studied in thirteen patients with myeloproliferative disorders. ADP induced aggregation was abnormal in two patients, but collagen induced aggregation was impaired in 11 patients. The concentrations of ATP and ADP in resting platelets in the patients ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1979-06-30 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::Seven mouse monoclonal antibodies have been produced against human melanoma tissue plasminogen activator (t-PA). They were specifically bound to 125I t-PA but not 125I urokinase (u-PA) and inhibited t-PA, but not u-PA, activity in plasminogen-rich 125I fibrin wells. Three of the antibodies directly inhibited the amido...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1985-02-18 00:00:00
abstract::Heparin therapy was monitored with the activated partial thromboplastin time (APTT) and with chromogenic substrate assays (factor Xa and factor IIa inhibition) in 100 plasma samples from 47 patients. Heparin concentrations were classified as being below, within or above a defined therapeutic range (TR; 0.2-0.55 units ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1987-10-28 00:00:00
abstract::Antibodies directed against ADAMTS13 have been detected in the majority of patients with acquired thrombotic thrombocytopenic purpura (TTP). We have previously localized a major antigenic determinant within the spacer domain of ADAMTS13. To identify the amino acid residues of the spacer domain that are involved in bin...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH06-03-0135
更新日期:2006-09-01 00:00:00
abstract::Lenalidomide, a derivate of thalidomide, has recently been approved in Europe for the treatment of patients with multiple myeloma. Although the substance has a better effect/side-effect profile, especially with regard to teratogenicity and neurotoxicity, the rate of therapy-induced thrombosis seems comparable to thali...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH08-01-0009
更新日期:2008-06-01 00:00:00
abstract::Bleeding time and platelet function tests were performed on 31 patients with progressive chronic renal failure (CRF) due to non-immunological (urological) causes, and compared with 22 healthy controls. Patients were classified as mild (plasma creatinine less than 300 mumol/l), moderate (300-600 mumol/l) or severe rena...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1988-08-30 00:00:00
abstract::Adhesion to collagen was investigated as a function of platelet age in rat platelets. Platelet adherence was measured using EDTA-containing platelet- rich plasma which was added to preparations of collagen fibers clamped between magnetic stirrers by recording changes in light transmission. The plot of light transmissi...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1976-11-30 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::Experiments were carried out to characterize the specificity of uptake of tPA in rat liver cells. Endocytosis in liver endothelial cells of the native carbohydrate variants of tissue plasminogen activator (tPA), and tPA inactivated by diisopropyl fluorophosphate was found to be competitive, suggesting that the determi...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1988-06-16 00:00:00
abstract::The emergency management of ST-elevation myocardial infarction (STEMI) involves treatment with dual-antiplatelet therapy (DAPT) and primary percutaneous coronary intervention (PPCI). Pain is generally treated with opiates, which may delay gastric transit and reduce DAPT absorption. We sought to assess the effect of mo...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0038-1629896
更新日期:2018-03-01 00:00:00
abstract::Protein C is a vitamin K-dependent serine protease zymogen in plasma which upon activation to activated protein C (APC) by thrombin down-regulates the clotting cascade by limited proteolysis of the procoagulant cofactors Va and VIIIa. In addition to its anticoagulant activity, APC also exhibits potent cytoprotective a...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH12-10-0760
更新日期:2013-04-01 00:00:00
abstract::Electrospray ionisation mass spectrometry was used to probe the structure of the new N-linked oligosaccharide in fibrinogen Kaiserslautern (gamma 380 Lys-->Asn). The mass increase of 2177 Da in the new beta chain indicated the attachment of a fully sialylated biantennary oligosaccharide on the new Asn residue; the exp...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-08-01 00:00:00
abstract::Venous thromboembolism (VTE) is a multifactorial disease. Major provoking factors (e. g. surgery, cancer, major trauma, and immobilisation) are identified in 50-60 % of patients, while the remaining cases are classified as unprovoked. However, minor predisposing conditions may be detectable in these patients, possibly...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH14-06-0563
更新日期:2015-06-01 00:00:00
abstract::Thrombin regulation in newborns remains incompletely understood. We studied tissue factor-initiated thrombin formation in cord plasma in vitro, and the effects of Factor V(Leiden) (FVL) heterozygosity on thrombin regulation both in vitro and in vivo in newborns. Pregnant women with known thrombophilia (n=27) were enro...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH05-05-0375
更新日期:2006-03-01 00:00:00
abstract::Patients with inflammatory bowel disease (IBD) are at higher risk of venous thromboembolism and coronary artery disease despite having a lower burden of traditional risk factors. Platelets from IBD patients release more soluble CD40 ligand (CD40L), and this has been implicated in IBD platelet hyper-activation. We here...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH16-02-0167
更新日期:2016-08-30 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::Induction of procoagulant factors in malignant cells is considered to be the major cause of coagulation disorders in cancer. Thrombomodulin (TM), a negative regulator of coagulation was also found to be expressed in cancer cells. We report here evidence for another anticoagulant, the endothelial cell protein C recepto...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-02-01 00:00:00