Abstract：
:Tissue-type plasminogen activator (t-PA) is a fibrin-specific agent which is used to treat acute myocardial infarction. Pharmacokinetically, t-PA is characterized by a rapid clearance from the circulation. In a previous study, we constructed variant forms of t-PA with genetic modifications at the fibronectin finger-like domain (finger domain) or at the kringle 1 domain (K1 domain). The finger modified variant, t-PA N37S.S38V.G39V.R40E. A41F.Q42S had about a 6.0-fold higher plasma half-life in vivo than wild-type t-PA. Two variants with modifications in the K1 domain, t-PA G161R.K162R.S165W and t-PA N115P, showed an improved kinetic parameters and a 2.2-fold higher plasma half-life in vivo than wild-type t-PA, respectively. To create a recombinant variant of t-PA with a higher enzymatic activity and a further prolonged half-life in vivo, the genes containing each modifications were joined and expressed in animal cells. The two variants, t-PA N37S.S38V.G39V.R40E.A41F.Q42S.G16 1R.K162R.S165W and t-PA N37S.S38V.G39V.R40E.A41F.Q42S.N11 5P, were purified from conditioned media and their biochemical, pharmacokinetic and thrombolytic profiles were investigated. Although the variant t-PA N37S.S38V.G39V.R40E.A41F.Q42S.G16 1R.K162R.S165W demonstrated an impaired enzymatic activity compared to the wild-type t-PA, the half-life of the variant, t-PA N37S.S38V.G39V.R40E.A41F.Q42S. N115P, following intravenous bolus injection in rabbits was considerably longer than that of finger-domain modified variants.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Yahara H,Matsumoto K,Maruyama H,Nagaoka T,Ikenaka Y,Yajima K,Fukao H,Ueshima S,Matsuo Osubject
Has Abstractpub_date
1994-12-01 00:00:00pages
893-9issue
6eissn
0340-6245issn
2567-689Xjournal_volume
72pub_type
杂志文章abstract：:We have studied 155 subjects, 48 normals, 36 diabetics without complications, 44 with complications and 27 patients with macroangiopathy. beta-Thromboglobulin (beta-TG) and platelet factor 4 (PF4) are elevated in the patients groups. There is no correlation between the plasma levels of beta-TG and the stages of either...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1984-12-29 00:00:00
abstract：:Genetic determinants of venous thromboembolism (VTE) in the African-American population are poorly characterised. It was recently shown that fibrinogen gamma gene (FGG) polymorphisms 10034C>T and 9340T>C influence VTE risk in the Caucasian population. In the African-American population these polymorphisms are common, ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2009-06-01 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：:Although associated with adverse outcomes in other cardiopulmonary diseases, limited evidence exists on the prognostic value of anaemia in patients with acute pulmonary embolism (PE). We sought to examine the associations between anaemia and mortality and length of hospital stay in patients with PE. We evaluated 14,27...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：10.1160/TH11-04-0208
更新日期：2011-08-01 00:00:00
abstract：:We investigated the molecular basis of hypofibrinogenaemia in a woman with a history of recurrent, pregnancy-associated bleeding, and miscarriage. She had a Clauss fibrinogen of 0.9 mg/ml and SDS PAGE of purified fibrinogen showed a normal pattern of chains. However careful inspection of reverse phase chain separation...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2000-09-01 00:00:00
abstract：:Women with a history of venous thromboembolism (VTE), thrombophilia or both may be at increased risk of thrombosis during pregnancy, but the optimal management strategy is not well defined in clinical guidelines because of limited trial data. A strategy of risk assessment and heparin prophylaxis was evaluated in pregn...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1160/th07-05-0329
更新日期：2007-12-01 00:00:00
abstract：:The clinical impact of in-stent thrombosis is high because it is associated with high mortality and 20 % of the patients suffer a recurrent event within the two following years. The aim of this study was to characterise the morphologic and proteomic profile of in-stent thrombi (IST) in comparison to thrombi developed ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH17-03-069
更新日期：2017-08-30 00:00:00
abstract：:Serine proteases are proteolytic enzymes with an active serine residue in their catalytic site. Kallikreins are a subgroup of the serine protease family and are known to have diverse physiological functions. The human tissue kallikrein gene family has now been fully characterized and includes 15 members, clustered in ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：2003-07-01 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：:Human high molecular weight kininogen (HK), a single chain plasma glycoprotein, serves as a cofactor in the contact system of blood coagulation. After cleavage by human plasma kallikrein, the nonapeptide bradykinin is released. The HK light chain (LC) contains coagulant activity, which requires both the ability to bin...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1992-04-02 00:00:00
abstract：:The aim was to investigate the perioperative risk of ischaemic and bleeding events in patients with coronary stents undergoing cardiac and non-cardiac surgery and how these outcomes are affected by the perioperative use of oral antiplatelet therapy. This was a multicentre, retrospective, observational study conducted ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：10.1160/TH14-05-0436
更新日期：2015-02-01 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：: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：: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：:Per cent aggregation, release and content of adenine nucleotides, and specific radioactivity were evaluated in citrated platelet-rich plasma (PRP) prepared from paired samples of maternal and cord blood. Platelets of newborn infants aggregated normally in response to highdose ADP (20 muM), strong collagen suspensions,...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1976-08-31 00:00:00
abstract：:Tissue factor is the primary initiator of coagulation cascade and plays an essential role in haemostasis and thrombosis. In addition, tissue factor and coagulation proteases contribute to many cellular responses via activation of protease activated receptors. The heart is an organ with high levels of constitutive tiss...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH14-03-0243
更新日期：2014-11-01 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：:We previously reported a monoclonal antibody named IF-43 that specifically recognizes thrombin-modified fibrinogen (desAA- and desAABB- fibrin monomer) bound with fibrinogen or other D(1) domain-containing plasmic fragments such as fragments X,Y, and D(1), but not intact fibrinogen or cross-linked fibrin degradation p...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2003-05-01 00:00:00
abstract：:Endotoxin (LPS) and interleukin-1 beta (IL-1 beta) increased in a dose-dependent manner the expression of tissue factor, an ubiquitous membrane-anchored glycoprotein that initiates blood coagulation at the surface of human umbilical vein endothelial cells (HUVEC and human peripheral blood mononuclear cells (PBMC). Ech...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1996-02-01 00:00:00
abstract：:Sixteen Danish unrelated thrombophilic families with plasma protein S deficiency of type 1 (or III) are currently under investigation in our laboratory for defects in the protein S alpha gene. The present paper describes a part of this work, which deals with the identification and phenotypical presentation of two uniq...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1996-08-01 00:00:00
abstract：:Arterial stenosis results in a complex pattern of blood flow containing an extremely fast flow in the throat of stenosis and a post-stenosis low flow. The fast flow generates high shear stress that has been demonstrated in vitro to activate and aggregate platelets. One potential problem of these in vitro studies is th...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2002-11-01 00:00:00
abstract：:Tissue factor (TF) markedly enhances the ability of factor VIIa (FVIIa) to cleave both macromolecular and small peptidyl substrates. Using soluble mutant TF (sTF) to investigate TF-enhanced FVIIa amidolytic activity in solution, we screened thirty-four commercially available peptidyl-p-nitroanilide substrates and foun...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1993-12-20 00:00:00
abstract：:To study the predictive value of coagulation markers concerning clinical outcome, prothrombin fragment F1.2 (F1.2), fibrin monomer antigen (FM), D-Dimer (DD), and fibrinogen were measured in plasma samples drawn 2 and 7 days after acute myocardial infarction (AMI) in 314 consecutive patients randomized in a clinical t...
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：1999-05-01 00:00:00
abstract：:Activation and signaling of circulating blood and vessel wall cells, as well as their direct adhesive interactions, are critical for the regulation of vascular homeostasis related to vasomotor responses, inflammation, hemostasis, and wound repair. Under conditions of stress, inflammation, or infection the targeting an...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：1999-08-01 00:00:00
abstract：:The development of venous thromboembolism (VTE), which includes deep-vein thrombosis and pulmonary embolism, may be associated with inherited or acquired risk factors that can be measured in plasma or DNA testing. The main inherited thrombophilias include the plasma deficiencies of the natural anticoagulants antithrom...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH15-06-0478
更新日期：2016-01-01 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：: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：:Recombinant human activated factor VII (rHuFVIIa) can reduce bleeding but may be associated with arterial thrombosis. We hypothesized that rHuFVIIa would increase the occurrence of cyclic flow reductions (CFR) and reduce intra-abdominal bleeding in an experimental model. An adapted Folts' model of carotid artery lesio...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2007-02-01 00:00:00
abstract：:In health, haemostasis and angiogenesis are tightly regulated processes, but may become deregulated in cancer. Recent evidence suggests that platelet activation may link these processes as platelets can release angiogenic factors such as vascular endothelial growth factor (VEGF). Furthermore, inflammation has also bee...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH03-11-0679
更新日期：2004-07-01 00:00:00
abstract：:1. Some of the guidelines on the nomenclature for the genotype of bacterial strains can be applied for recommendations on the nomenclature for the description of recombinant mutant fibrinolytic constructs. 2. In view of the usually different size of genomic DNA and corresponding cDNA, it is recommended to employ a dis...
journal_title：Thrombosis and haemostasis
pub_type： 指南,杂志文章
doi：
更新日期：1990-12-28 00:00:00
