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    Method of diagnosing an increased risk of thrombus associated disease by detecting a certain t-PA polymorphism
    1.
    发明授权
    Method of diagnosing an increased risk of thrombus associated disease by detecting a certain t-PA polymorphism 失效
    通过检测某种t-PA多态性来诊断血栓相关疾病风险增加的方法

    公开(公告)号：US5994080A

    公开(公告)日：1999-11-30

    申请号：US29023

    申请日：1998-02-20

    申请人： Diederick Egberstus Grobbee ,  Cornelis Kluft

    发明人： Diederick Egberstus Grobbee ,  Cornelis Kluft

    IPC分类号： C12N15/09 ,  C12Q1/68 ,  C07H21/02 ,  C12P19/34

    CPC分类号： C12Q1/6883 ,  C12Q2600/156

    摘要： Blood clot formation is the key event in myocardial infarction. Besides increased coagulation, failure in blood clot lysis can induce undesired coronary thrombosis. Plasmin is essential for degradation of fibrin clots. Tissue-type plasminogen activator (t-PA) is the serine protease that converts plasminogen into plasmin. The association of the Alu insertion/deletion polymorphism in intron h of the t-pA gene to the risk of myocardial infarction was evaluated. Subjects with a documented history of myocardial infarction (n=162) and controls (n=258) were drawn from the Rotterdam Study, a population-based cohort study of 7983 subjects of 55 years or older. Allele frequencies were 0.54 for the insertion allele (t-PA Alu-h I) and 0.46 for the deletion allele, and were in Hardy Weinberg equilibrium. Among subjects that were homozygous for the insertion (n=138) were more than twice as many subjects with myocardial infarction compared to those homozygous (n=75) for the deletion (relative risk of 2.04, (95% CI 1.03-4.03), adjusted for age, gender, smoking, total cholesterol, HDL cholesterol, systolic and diastolic blood pressure and body mass index). Our results provide strong evidence for an association of a particular allele, t-PA Alu-h I, of the t-PA gene with the occurrence of myocardial infarction.

    摘要翻译： PCT No.PCT / EP96 / 03652。 371日期：1998年2月20日 102（e）1998年2月20日PCT PCT 1996年8月19日PCT公布。 出版物WO97 / 07240 日期1997年2月27日血液凝块形成是心肌梗死的关键事件。 除了凝血增加外，血块溶解失败也可能引起不良的冠状动脉血栓形成。 纤溶酶是纤维蛋白凝块降解所必需的。 组织型纤溶酶原激活剂（t-PA）是将纤溶酶原转化成纤溶酶的丝氨酸蛋白酶。 评估了t-pA基因内含子h中Alu插入/缺失多态性与心肌梗塞风险的关联。 从鹿特丹研究中抽取具有记录的心肌梗死史（n = 162）和对照组（n = 258）的受试者，这项研究是针对553岁或以上的7983例受试者的基于人群的队列研究。 插入等位基因（t-PA Alu-h I）的等位基因频率分别为0.54和缺失等位基因的等位基因频率分别为0.46和Hardy Weinberg平衡。 与纯合子（n = 75）相比，在插入（n = 138）中纯合子的受试者中，心肌梗死受试者的数目是两倍以上（相对危险度为2.04，（95％CI 1.03-4.03））， 调整年龄，性别，吸烟，总胆固醇，HDL胆固醇，收缩压和舒张压和体重指数）。 我们的结果为t-PA基因的特定等位基因t-PA Alu-h I与心肌梗塞发生的关联提供了有力的证据。

    100KDa protein from blood which binds to and inhibits the activity of plasminogen activators
    2.
    发明授权
    100KDa protein from blood which binds to and inhibits the activity of plasminogen activators 失效
    来自血液的100KDa蛋白质结合并抑制纤溶酶原激活物的活性

    公开(公告)号：US5004802A

    公开(公告)日：1991-04-02

    申请号：US884418

    申请日：1986-07-11

    申请人： Cornelis Kluft

    发明人： Cornelis Kluft

    IPC分类号： A61K35/14 ,  A61K35/16 ,  A61K38/00 ,  A61K38/16 ,  A61K38/55 ,  C07K14/745 ,  C07K14/81

    CPC分类号： C07K14/8132 ,  A61K38/00 ,  Y10S530/829

    摘要： A protein called PA binding protein has been isolated which binds specifically and reversibly to tissue plasminogen activator. The protein is characterized by a molecular mass of about 100,000 daltons, and electrophoretic mobility in agarose at pH 8.6 equal to that of plasma .beta.-globulins and an isoelectric point of 6.5 to 7.0. The protein is thermostable up to at least 56.degree. C. and is cleared from the circulation with a half life on the order of days.

    摘要翻译： 已经分离出称为PA结合蛋白的蛋白质，其特异性和可逆地结合于组织纤溶酶原激活物。 该蛋白质的特征在于约100,000道尔顿的分子量，并且在pH 8.6的琼脂糖中的电泳迁移率等于血浆β-球蛋白的电泳迁移率，等电点为6.5至7.0。 该蛋白质耐热至多达56℃，并从循环中清除半衰期约为几天。