Abstract：
:Antithrombin (AT) is a serpin capable of trapping thrombin (IIa) in a stable and covalent complex. Complex formation is prevented by leukocyte elastase (LE) cleavage near the AT reactive centre. We mutated the known LE cleavage sites of AT to explore the possibility of producing an LE-resistant AT molecule. Initially, six rabbit AT variants differing only at residue 390 (P4) were generated in a cell-free system, and gel-based assays were used to assess IIa-mediated complex formation and LE-mediated cleavage of the variants. Substitution of charged residues (Glu or Arg) reduced complex formation by 50-60%, while the Ser variant was incapable of inhibiting thrombin; LE reactivity was less affected. The least (Trp) and most (Ser) affected variants were expressed in COS-1 cells. Again, the Ser variant was incapable of detectably reducing the rate of thrombin-mediated amidolysis while the Trp variant inhibited thrombin at a slightly reduced rate (-28%). LE inactivated the Trp variant and the wild-type AT to a similar extent. Recreation of the Trp mutation in COS-derived human AT showed similar results. Since retention of LE-sensitivity could have arisen due to cleavage at Val389 (P5), we produced and characterized a human AT substitution mutant with Trp at both P4 and P5. This variant showed a slight reduction in thrombin inhibitory activity (-22%), but remained susceptible to LE inactivation. These results suggest either that LE cleaves at secondary sites if its primary cleavage sites are blocked, or that the substrate specificity of LE differs in polypeptides as compared to peptide substrates.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Cunningham MA,Blajchman MA,Sheffield WPdoi
10.1016/s0049-3848(97)00228-4subject
Has Abstractpub_date
1997-10-15 00:00:00pages
171-81issue
2eissn
0049-3848issn
1879-2472pii
S0049384897002284journal_volume
88pub_type
杂志文章abstract：:beta-Factor XIIa (beta-XIIa, Mr approximately 30,000) was isolated from human plasma by a procedure which utilized, as an initial step, the adsorption of Factor XII to celite. Activation of Factor XII and subsequent release of beta-XIIa was brought about by the proteolytic action of co-adsorbed kallikrein. Two success...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(82)90231-6
更新日期：1982-02-15 00:00:00
abstract：INTRODUCTION:Medically ill, hospitalized patients are at increased risk for venous thromboembolism (VTE) after discharge. This study aimed to examine thromboprophylaxis patterns, risk factors, and post-discharge outcomes. METHODS:This was a retrospective claims analysis involving administrative claims data and in-pati...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2013.08.013
更新日期：2013-11-01 00:00:00
abstract：INTRODUCTION:Extracellular histones are reported to increase thrombin generation in the plasma and induce endothelial cell death in vitro. These effects of histones were suggested to involve histone-induced inhibition of TM-dependent activated protein C (APC) generation. Therefore, we hypothesized that TM alfa, a recom...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2017.10.019
更新日期：2017-12-01 00:00:00
abstract：INTRODUCTION:Patients with stable coronary artery disease (CAD) are at risk of arterial thrombosis causing myocardial infarction. Detection of global haemostatic markers of hypercoagulability and hypofibrinolysis may be important for risk stratification and individualised treatment. We examined overall haemostatic pote...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2013.03.015
更新日期：2013-05-01 00:00:00
abstract：INTRODUCTION:In patients with new symptoms in a leg previously affected by deep vein thrombosis (DVT), the presence of thrombus on ultrasound cannot be assumed to be due to recurrent thrombosis. Several parameters have been suggested to differentiate between acute and chronic thrombus on ultrasound, including measureme...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2005.02.011
更新日期：2006-01-01 00:00:00
abstract：:A simple and discriminating assay for the determination of the fast-acting plasminogen activator inhibitor (PAI) activity in human plasma is described. The method is based on the inhibition of purified tissue plasminogen activator (tPA) by plasma diluted with a PAI-depleted plasma and the subsequent measurement of res...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(89)90250-8
更新日期：1989-11-01 00:00:00
abstract：BACKGROUND:Critical care patients are prone to venous thromboembolism (VTE) and, thus, pharmacological thromboprophylaxis is generally advised. Low-molecular weight heparins (LMWHs) have become the drug of choice in ICU patients, since their predictable and reproducible dose response. Monitoring their pharmacological e...
journal_title：Thrombosis research
pub_type： 杂志文章,meta分析
doi：10.1016/j.thromres.2015.12.016
更新日期：2016-03-01 00:00:00
abstract：:Ovarian hyperstimulation syndrome (OHSS) affects 5% of IVF cycles and incurs a 100-fold increase in risk of venous thrombosis over natural conceptions. Identification of women at risk of OHSS can be achieved using antral follicle count (AFC) and anti-Müllerian hormone (AMH). For those women with a high AFC or AMH comb...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/S0049-3848(13)00023-6
更新日期：2013-01-01 00:00:00
abstract：:The effects of desmopressin and dextran on haemostasis and fibrinolysis were studied in four healthy volunteers. Both drugs were compared to placebo, each volunteer being subject to four experiments. Dextran 70 (30 g i.v.) moderately decreased VIII:C and vWF:Ag and slightly increased antithrombin III, also when haemod...
journal_title：Thrombosis research
pub_type： 临床试验,杂志文章
doi：10.1016/0049-3848(91)90009-l
更新日期：1991-06-01 00:00:00
abstract：:Whilst the term cancer associated thrombosis (CAT) offers an overarching term for all thrombotic events encountered during the cancer journey, the reality is that this is a far too simplistic reflection of a complex multifactorial process occurring within a heterogeneous population. The management of CAT needs to cons...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/S0049-3848(16)30115-3
更新日期：2016-04-01 00:00:00
abstract：:The release of arachidonic acid, and its subsequent conversion to thromboxane A2, is an important component of platelet activation. The precise mechanism of arachidonic acid release is unknown although cytosolic phospholipase A2 (cPLA2) has been implicated. In the present study the effects of three agonists, the serin...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/s0049-3848(98)00097-8
更新日期：1998-10-01 00:00:00
abstract：:Clinically unsuspected pulmonary embolism (UPE) is frequently diagnosed in cancer patients undergoing routine computed tomography scans for staging purposes or treatment response evaluation. The reported incidence of UPE ranges from 1% to 5% which probably represents an underestimation. A significant proportion of can...
journal_title：Thrombosis research
pub_type： 杂志文章,评审
doi：10.1016/S0049-3848(14)50028-X
更新日期：2014-05-01 00:00:00
abstract：:A validated method for assessing hemostasis in vivo is critical for testing the hemostatic efficacy of therapeutic agents in preclinical animal models and in patients with inherited bleeding disorders, such as von Willebrand disease (VWD) and hemophilia A, or with acquired bleeding disorders such as those resulting fr...
journal_title：Thrombosis research
pub_type： 杂志文章,评审
doi：10.1016/j.thromres.2012.02.035
更新日期：2012-05-01 00:00:00
abstract：:Selected coagulation and fibrinolytic parameters were assessed in 40 insulin dependent diabetes mellitus patients with varying degrees of metabolic control; 30 healthy subjects matched for age and sex formed the control group. Activated Partial Thromboplastin Time, Prothrombin Time, Fibrinogen, Factor VII, Antithrombi...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(92)90068-l
更新日期：1992-09-15 00:00:00
abstract：BACKGROUND:Clauss fibrinogen assay (CFA) is widely used as a screening test to detect fibrinogen disorders. However, CFA alone cannot distinguish quantitative and qualitative defects because it depends on functional fibrinogen activity (Ac), and fibrinogen antigen (Ag) determination is required to classify fibrinogen d...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2018.12.018
更新日期：2019-02-01 00:00:00
abstract：:Extended half-life (EHL) products have shown robust efficacy in clinical trials, whilst allowing for less intense treatment regimens when compared with standard half-life products. Regimen optimisation with EHL products could lead to further improvements in bleeding rates, quality of life and reductions in treatment b...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2019.12.012
更新日期：2020-12-01 00:00:00
abstract：:Endothelial cells synthesize and release different proteins involved in their function, and some of these proteins may play important roles in the cellular response to injury, infection, or glucocorticoids. We have examined the profile of proteins released from rabbit coronary microvascular endothelial (RCME) and huma...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(90)90202-n
更新日期：1990-01-01 00:00:00
abstract：:In a double-blind, placebo-controlled trial of 40 patients requiring aortocoronary vene transplant surgery, prostacyclin (PGI2) was infused in a dose of 8 ng/kg/min throughout cardiopulmonary bypass. When compared with the placebo-group, the patients treated with PGI2 were found to have significantly higher platelet c...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(83)90093-2
更新日期：1983-11-15 00:00:00
abstract：BACKGROUND:The AMPLIFY trial found significantly lower major bleeding (MB) and similar recurrent venous thromboembolism (VTE) risks associated with apixaban vs warfarin among patients with VTE. OBJECTIVES:To compare MB, clinically-relevant non-major (CRNM) bleeding, and recurrent VTE risks among clinically-relevant su...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2020.11.039
更新日期：2020-12-08 00:00:00
abstract：:A prolongation of the thrombin clotting time by at least 25% was found in the presence of 8 of 26 IgG myeloma proteins, 2 of 5 IgA proteins and 1 of 10 macroglobulins, in a concentration of 10 mg/ml. Normal pooled immunoglobulin in concentrations up to 83 mg/ml were inactive. 2 IgG and 2 IgM monoclonal immunoglobulins...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(84)90315-3
更新日期：1984-07-01 00:00:00
abstract：:Venous thromboembolism (VTE) is a preventable disease, yet it is one of the leading causes of death among patients with cancer. Improving risk stratification mechanisms will allow us to personalize thrombo-prophylaxis strategies. We sought to evaluate Collagen and Thrombin Activated Platelets (COAT-platelets) as well ...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2015.10.004
更新日期：2015-12-01 00:00:00
abstract：:The inability of the heparin-antithrombin complex to inhibit fibrin-bound thrombin limits the utility of heparin for treatment of arterial thrombosis. In contrast with heparin, melagatran, a direct thrombin inhibitor (DTI), is equally effective at inhibiting fluid-phase thrombin and thrombin bound to fibrin. This refl...
journal_title：Thrombosis research
pub_type： 杂志文章,评审
doi：10.1016/s0049-3848(03)00251-2
更新日期：2003-07-15 00:00:00
abstract：:The effect of red wine drinking was tested on fibrinolytic parameters and blood cells in nine healthy students at rest and after acute exercise. The subjects were randomly assigned in a crossover design to one of three treatment regimes: control situation, low-dose wine group, and high-dose wine group. Blood samples w...
journal_title：Thrombosis research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1016/s0049-3848(99)00120-6
更新日期：1999-12-01 00:00:00
abstract：:The Coa-set Fibrin Monomer test (CFM-test) is a quantitative method for determination of soluble fibrin in plasma. The fibrin standard of the CFM-test is produced by bathroxobin conversion of purified fibrinogen to fibrin. Plasma treated with minute amounts of thrombin may be considered as a more physiological way of ...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(93)90139-f
更新日期：1993-11-15 00:00:00
abstract：:The interaction of platelets with collagen involves short aminoacid sequences which recur along the fibres. Platelet aggregation by collagen and serotonin release is inhibited by a synthetic octapeptide LYS-PRO-GLY-GLU- PRO-GLY-PRO-LYS- derived from type III collagen. In contrast, this octapeptide inhibits only weakly...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(83)90061-0
更新日期：1983-12-15 00:00:00
abstract：:Blood platelets have recently been shown to express PYK2, a nonreceptor tyrosine kinase belonging to the FAK gene family. In this study, we examined the involvement of protein kinase C (PKC) in PYK2-related responses in human platelets. While PYK2 tyrosine phosphorylation induced by thrombin was inhibited by preincuba...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/s0049-3848(98)00188-1
更新日期：1999-03-15 00:00:00
abstract：:Patients with hematologic malignancies have an increased risk of venous thromboembolism (VTE), particularly at diagnosis and during the treatment with chemotherapy, asparaginase or immunomodulatory drugs (IMiDs). A disease-dependent hypercoagulable condition associated with other risk factors like drugs, central venou...
journal_title：Thrombosis research
pub_type： 杂志文章,评审
doi：10.1016/j.thromres.2011.11.034
更新日期：2012-03-01 00:00:00
abstract：:A rapid method is described for the production of a human marrow cell suspension highly enriched in megakaryocytes. These concentrates were incubated with radiolabelled amino-acids, and cell lysates were then analysed for fibrinogen synthesis. Neosynthesized proteins were detected by immunoprecipitation, immuno-affini...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(85)90133-1
更新日期：1985-05-15 00:00:00
abstract：BACKGROUND:Clinical and epidemiological studies have associated selective COX-2 inhibitors with an increased risk of cardiovascular events. There are no clinical studies on the possible effects of these drugs on secondary hemostasis. The hypothesis for this study is that the use of selective COX-2 inhibitors could affe...
journal_title：Thrombosis research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1016/j.thromres.2009.01.017
更新日期：2009-06-01 00:00:00
abstract：:The inhibition of one- and two-chain forms of tissue-type plasminogen activator by a series of peptide derivatives of arginine chloromethyl ketone was studied. Both forms of the enzyme were inhibited by such reagents at varying rates, dependent on the peptide sequence of the inhibitor. The order of relative effectiven...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(86)90133-7
更新日期：1986-10-15 00:00:00
