Abstract：
:Staphylokinase is a potent highly fibrin-selective thrombolytic agent, but it induces a humoral immune response in most treated patients. Staphylokinase-specific T-lymphocytes can be found in normal healthy individuals, from whom a large panel of staphylokinase-specific T-cells were cloned. The staphylokinase amino acid sequence 71-87 was widely recognized, as it induced proliferation of T-cell clones isolated from 90% of the donors. Computer modeling of this area, threaded as 11-mer peptides within the peptide-binding groove of the major HLA-DR alleles, indicated two putative partially overlapping binding sequences. The region-(71-87)-specific T-cell clones recognized either one or the other minimal peptide, confirming that both sequences could be functional T-cell epitopes. Furthermore, to guide the mutagenesis to eliminate T-cell reactivity, the contribution of each residue to the HLA-DR-anchoring and T-cell receptor exposure was evaluated for both binding motifs. Computer calculations combined with functional assays resulted in the design of staphylokinase-variants, including 2 to 4 amino acid substitutions in the region 71-87. These variants were no longer recognized by the region-(71-87)-specific T-cell clones, and importantly no new staphylokinase-variant-specific cellular immune response could be measured.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Warmerdam PA,Plaisance S,Vanderlick K,Vandervoort P,Brepoels K,Collen D,De Maeyer Mkeywords:
subject
Has Abstractpub_date
2002-04-01 00:00:00pages
666-73issue
4eissn
0340-6245issn
2567-689Xjournal_volume
87pub_type
杂志文章abstract：:Our previous study has shown that Toll-like receptor 4 (TLR4) and its signalling pathway contribute to anti-β₂-glycoprotein I/β₂-glycoprotein I (anti-β₂GPI/β₂GPI)-induced tissue factor (TF) expression in human acute monocytic leukaemia cell line THP-1 and annexin A2 (ANX2) is involved in this pathway. However, its dow...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH11-04-0229
更新日期：2011-12-01 00:00:00
abstract：:Elderly patients have previously been shown to have an increased plasma concentration of tissue plasminogen activator (t-PA) antigen (t-PA Ag). Since the concentration of t-PA Ag depends on both free t-PA and t-PA complexed with inhibitors, mainly plasminogen activator inhibitor (PA inhibitor), we have investigated th...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1986-06-30 00:00:00
abstract：:The use of exogenous oestrogen in women with otherwise unprovoked venous thromboembolism (VTE) could be considered sufficient explanation to classify VTE as provoked if the risk of recurrent VTE after 3-6 months of anticoagulant treatment is similar to the risk of recurrent VTE observed after a surgery or prolonged im...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：10.1160/TH09-10-0685
更新日期：2010-09-01 00:00:00
abstract：:Previous studies have reported that the platelets of healthy term neonates have either diminished or normal reactivity compared to the platelets of adults. To circumvent the methodologic problems of previous studies, we used a whole blood flow cytometric method to study neonatal platelet reactivity to thrombin, a comb...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1994-12-01 00:00:00
abstract：:Analysis of platelet membrane proteins and glycoproteins by SDS polyacrylamide gel electrophoresis was carried out before and after treatment with thrombin. Extended incubation with thrombin (in the presence of EDTA or adenosine, which inhibit aggregation) produced extensive changes in the bands observed. With incuba...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1977-06-30 00:00:00
abstract：:Data on anti-platelet therapy (APT) for prevention of atherothrombotic events in thrombocytopaenic cancer patients is lacking. We aimed to identify patient and physician characteristics associated with APT management in thrombocytopaenic patients with haematological malignancy. A clinical vignette-based experiment was...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/s-0038-1676520
更新日期：2019-01-01 00:00:00
abstract：:Forty-eight patients with acute proximal deep vein thrombosis (DVT) were randomised to intravenous infusions for 4 to 6 days with melagatran, a novel synthetic low molecular weight thrombin inhibitor, or unfractionated heparin adjusted by the activated partial thromboplastin time (APTT). The aim of the study was to in...
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：1999-03-01 00:00:00
abstract：:Current data suggests that the risk of venous thromboembolism (VTE) in patients with non-Hodgkin lymphoma (NHL) is comparable to that observed in patients with solid tumours, although more robust confirmatory analyses are required. With that in mind, we investigated the occurrence of VTE in a pooled analysis of 12 "Fo...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH16-11-0895
更新日期：2017-04-27 00:00:00
abstract：:We have evaluated the effect of plasminogen activators (t-PA and urokinase) on an experimental model of disseminated intravascular coagulation (DIC) in rabbits by injection of 20 micrograms/kg/h of E. coli lipopolysaccharide during 6 h t-PA (0.2 mg/kg and 0.7 mg/kg), urokinase (3000 U/kg/h) and saline (control) were g...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-12-01 00:00:00
abstract：:Although there is considerable evidence that platelet activation is associated with polymerization of actin, it is not known whether there is some pre-existing F-actin even before activation. We have examined the state of actin polymerization in nonactivated platelets by deoxyribonuclease assay of G-actin and total ac...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1982-10-29 00:00:00
abstract：:In two randomized double-blind studies perioperative bleeding complications and thromboembolic events were assessed in 189 patients (pts) undergoing elective visceral surgery after subcutaneous administration of a low molecular weight (LMW) heparin fragment (KABI fragment 2165) or unfractionated (UF) heparin. The firs...
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：1986-12-15 00:00:00
abstract：:Plasminogen activator inhibitor-1 (PAI-1) controls the regulation of the fibrinolytic system in blood by inhibiting both urokinase-type and tissue-type plasminogen activators. Enhanced levels of PAI-1 are related to pathological conditions associated with hypoxia or hyperinsulinemia. In this study, we investigated the...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2007-08-01 00:00:00
abstract：:Standard pharmacokinetic (PK) assessments are demanding for persons with hemophilia A, requiring a 72hr washout and 5-11 timed blood samples. A no-washout, single-clinic visit, sparse sampling population PK (PPK) protocol is an attractive alternative. Here, we compared PK parameters obtained with a traditional washout...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验
doi：10.1055/a-1376-0970
更新日期：2021-01-27 00:00:00
abstract：:A nutritionally induced obesity model was used to investigate the modulation of fibrinolytic and gelatinolytic activity during the development of adipose tissue. Five week old male mice were fed a standard fat diet (SFD, 13% kcal as fat) or a high fat diet (HFD, 42% kcal as fat) for up to 15 weeks. The HFD resulted in...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2002-08-01 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：:The risk of acute cardiovascular events is highest during morning hours, and platelet activity peaks during morning hours. The effect of timing of aspirin intake on circadian rhythm and morning peak of platelet reactivity is not known. It was our objective to evaluate the effect of timing of aspirin intake on circadia...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,随机对照试验
doi：10.1160/TH14-05-0453
更新日期：2014-12-01 00:00:00
abstract：:Microvascular endothelial damage underlies the pathological changes in haemorrhagic colitis and the haemolytic uraemic syndrome (HUS) caused by enterohaemorrhagic Escherichia coli (EHEC). Shiga toxins (Stxs) are presently the best characterised EHEC virulence factors that can cause the microvascular endothelium injury...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH05-04-0265
更新日期：2005-08-01 00:00:00
abstract：:Elucidation of the pathophysiological basis of platelet disorders in murine models requires a reliable method for the frequent determinations of platelet counts in individual mice. Here, we present a rapid, reproducible and accurate flow cytometric method for enumeration of platelets that involves fluorescent staining...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-08-01 00:00:00
abstract：:The inhibitory capacity of antithrombin III (AT III) was measured by a quantitative method independent of the velocity of inhibition. When AT III was in excess of thrombin in plasma or in purified system the capacity of inhibitor decreased quantitatively in proportion to the amount of thrombin neutralized. Heparin pre...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1977-08-31 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：:Atherosclerosis is a prevalent inflammatory condition and a frequent cause of morbidity and mortality worldwide. Macrophages are among the key immune cells driving lesion formation in the arterial wall. They have therefore evolved as potential targets for therapeutic strategies. Understanding of the different macropha...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-0039-1692665
更新日期：2019-08-01 00:00:00
abstract：:We performed a case-controlled study to investigate whether the FV Leiden mutation and the C > T677 polymorphism of the 5, 10 methylene tetrahydrofolate reductase (MTHFR) are associated with the occurrence of preeclampsia in 96 otherwise healthy preeclamptic women and 129 parous women as controls. FV Leiden carriers w...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-06-01 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：:Current thrombolytic strategies have a number of important shortcomings including resistance to recanalization and development of acute reocclusion. The purpose of this study was to investigate whether the lysis of venous thrombi by streptokinase could be enhanced by SR 46349, a novel 5-HT2 receptor antagonist, or clo...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1993-03-01 00:00:00
abstract：:Proteolysis of connective tissue by enzymes such as PMN-elastase (PMNE) is a crucial step during inflammation and metastasis. Semisynthetic sulfated carbohydrates (SC) were shown to exhibit potent antiinflammatory and antimetastatic activity in vivo. The aim of the present study was to examine whether interferences wi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2003-05-01 00:00:00
abstract：:The effect of shear rate and fibrinogen concentration on adenosine diphosphate-induced aggregation of suspensions of washed human platelets in Poiseuille flow at 23 degrees C was studied using a previously described double infusion technique and resistive particle counter size analysis. Using suspensions of multiple-c...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1994-01-01 00:00:00
abstract：:Advanced glycation end-products (AGEs) interact with their receptor RAGE, leading to an inflammatory state. We investigated the role of RAGE in postischaemic leukocyte adhesion after myocardial infarction and its effect on postischaemic myocardial function. Wildtype (WT), ICAM-1-/-, RAGE-/- or ICAM-1/RAGE-/- mice unde...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH15-11-0898
更新日期：2016-08-01 00:00:00
abstract：:To investigate the inhibitory mechanism of tissue factor pathway inhibitor (TFPI), an attempt was made to examine the inhibitory activity of TFPI toward the factor VIIa-truncated tissue factor (TF1-219) complex, which lacks its transmembrane and cytoplasmic domains. Factor VIIa-TF1-219 activity was significantly inhib...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-03-01 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：:Noninvasive diagnosis of deep vein thrombosis (DVT) is based on ultrasound examination of the leg veins, usually restricted to only compression of the proximal veins (CUS). Patients with negative CUS findings require a second examination or a combination with other tests, which impairs clinical efficiency. In this pro...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2003-02-01 00:00:00
