公开(公告)号：US20140023635A1

公开(公告)日：2014-01-23

申请号：US13995976

申请日：2011-12-21

申请人： Pavel Hamet ,  Johanne Tremblay ,  Ondrej Seda ,  Stephen Macmahon ,  John Chalmers

发明人： Pavel Hamet ,  Johanne Tremblay ,  Ondrej Seda ,  Stephen Macmahon ,  John Chalmers

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6883 ,  A61K31/00 ,  C12Q2600/156

摘要： The invention provides with means to predict, in subjects affected by type-2-diabetes (T2D), the probability of developing complications related to the disease. The invention involves (1) identification of genetic features such as single nucleotide polymorphisms (SNPs) for the establishment of a patient profile that can be used for prediction of complications associated with T2D. Signature profiles comprising a combination of SNPs which have greater predictive value for prognosticating particular types of complications, such as, stroke, myocardial infarction and kidney complications associated with T2D are further described. Compositions and kits that can be used with a set of complementary phenotypic markers to evaluate the risk for an individual affected by T2D to develop complications related to the disease and to evaluate the likelihood that an individual affected by type 2 diabetes type will benefit from treatments that collectively aim to reduce the risk of developing such complications.

摘要翻译： 本发明提供了在受2型糖尿病（T2D）影响的受试者中预测发生与该疾病相关的并发症的可能性的手段。 本发明涉及（1）鉴定用于建立可用于预测与T2D相关并发症的患者概况的单核苷酸多态性（SNP）等遗传特征。 进一步描述包括具有预测特定类型并发症（例如中风，心肌梗死和与T2D相关的肾并发症）的更大预测价值的SNP的组合的签名曲线。 可用于一组互补表型标志物的组合物和试剂盒，以评估受T2D影响的个体发生与该疾病相关的并发症的风险，并评估受2型糖尿病类型影响的个体可能受益于 共同旨在降低发生此类并发症的风险。

公开(公告)号：US20120134981A1

公开(公告)日：2012-05-31

申请号：US13237707

申请日：2011-09-20

申请人： Pavel HAMET ,  Johanne Tremblay ,  Ondrej Seda ,  Stephen MaCmahon ,  John Chalmers

发明人： Pavel HAMET ,  Johanne Tremblay ,  Ondrej Seda ,  Stephen MaCmahon ,  John Chalmers

IPC分类号： A61K39/395 ,  A61P9/12 ,  A61K31/713 ,  A61P9/10 ,  C40B20/00 ,  A61K31/7088

CPC分类号： C12Q1/6883 ,  C12Q2600/118 ,  C12Q2600/156 ,  C12Q2600/172

摘要： The invention provides means and methods to predict, in subjects affected by type II diabetes (T2D), the probability of developing complications which include, but are not limited to, micro/macrovascular disorder, hypertension, neuropathy, atrial fibrillation, nephropathy and other major adverse cardiovascular events (MACE) that are associated with the disease, by detecting one or more genetic features. The genetic features that are useful in prediction include, but are not limited to, genes, single nucleotide polymorphisms (SNPs) and other genomic markers. The invention further involves characterizing individuals based on the probability of developing complications related to T2D, such as, micro/macrovascular disorder, hypertension, neuropathy, atrial fibrillation, nephropathy or MACE, based on the identification of one or more aforementioned genetic features. Also described are combinations and kits for carrying out the above-described methods.

摘要翻译： 本发明提供了在受II型糖尿病（T2D）影响的受试者中预测发生并发症的可能性的手段和方法，其包括但不限于微/大血管病，高血压，神经病，心房颤动，肾病等主要 通过检测一种或多种遗传特征与疾病相关的不良心血管事件（MACE）。 在预测中有用的遗传特征包括但不限于基因，单核苷酸多态性（SNP）和其他基因组标记。 本发明还涉及基于识别一个或多个上述遗传特征，基于与T2D相关的并发症的发生概率，例如微/大血管障碍，高血压，神经病变，心房颤动，肾病或MACE，来表征个体。 还描述了用于实施上述方法的组合和试剂盒。

公开(公告)号：US20110158979A1

公开(公告)日：2011-06-30

申请号：US12997621

申请日：2009-06-15

申请人： Pavel Hamet ,  Johanne Tremblay ,  Ondrej Seda ,  Stephen Macmahon ,  John Chalmers

发明人： Pavel Hamet ,  Johanne Tremblay ,  Ondrej Seda ,  Stephen Macmahon ,  John Chalmers

IPC分类号： A61K39/395 ,  C12Q1/68 ,  C40B30/00 ,  C40B40/06 ,  A61K31/7105 ,  A61P3/10

CPC分类号： C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/172

摘要： The invention provides with means to predict, in subjects affected by type 2 diabetes (T2D), the probability of developing complications related to the disease. The invention involves 1) use of genetic features (SNPs, STRs, or other genomic markers) together with other chromosomal features and phenotypic information to establish a patient profile specifically developed for prediction of complications of T2D 2) use of a set of SNPs allowing to discriminate between individuals according to their descent. The invention also provides with methods for characterizing and selecting, within a population of subjects with type-2 diabetes, subjects that are suited for clinical trials based on the identification of one or more genetic features. Also described are combinations and kits for carrying out the above-described methods.

摘要翻译： 本发明提供了在受2型糖尿病（T2D）影响的受试者中预测发生与该疾病相关的并发症的可能性的手段。 本发明涉及1）使用遗传特征（SNP，STR或其他基因组标记）以及其他染色体特征和表型信息来建立专门为预测T2D并发症而开发的患者概况2）使用一组允许 根据他们的血统区分个人。 本发明还提供了在基于识别一种或多种遗传特征的情况下，在具有2型糖尿病的受试者群体中表征和选择适合于临床试验的受试者的方法。 还描述了用于实施上述方法的组合和试剂盒。

公开(公告)号：US20100099091A1

公开(公告)日：2010-04-22

申请号：US12457555

申请日：2009-06-15

申请人： Pavel Hamet ,  Johanne Tremblay ,  Ondrej Seda ,  Stephen Macmahon ,  John Chalmers

发明人： Pavel Hamet ,  Johanne Tremblay ,  Ondrej Seda ,  Stephen Macmahon ,  John Chalmers

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/172

摘要： The invention provides with means to predict, in subjects affected by type 2 diabetes (T2D), the probability of developing complications related to the disease. The invention involves 1) use of genetic features (SNPs, STRs, or other genomic markers) together with other chromosomal features and phenotypic information to establish a patient profile specifically developed for prediction of complications of T2D 2) use of a set of SNPs allowing to discriminate between individuals according to their descent. A preferred set of genomic markers selected for their association with complications of T2D is provided that can be used with a set of complementary phenotypic markers to evaluate the risk for an individual affected by T2D to develop complications related to the disease and to evaluate the likelihood that an individual affected by T2D type will benefit from treatments reducing the risk of developing such complications.

摘要翻译： 本发明提供了在受2型糖尿病（T2D）影响的受试者中预测发生与该疾病相关的并发症的可能性的手段。 本发明涉及1）使用遗传特征（SNP，STR或其他基因组标记）以及其他染色体特征和表型信息来建立专门为预测T2D并发症而开发的患者概况2）使用一组允许 根据他们的血统区分个人。 提供了选择与T2D并发症相关联的一组优选的基因组标记，其可与一组互补表型标志物一起使用，以评估受T2D影响的个体的风险，以发展与该疾病相关的并发症，并评估其可能性 受T2D型影响的个体将受益于减少发生此类并发症风险的治疗。

公开(公告)号：US20100136540A1

公开(公告)日：2010-06-03

申请号：US12457556

申请日：2009-06-15

申请人： Pavel Hamet ,  Johanne Tremblay ,  Ondrej Seda ,  Stephen Macmahon ,  John Chalmers

发明人： Pavel Hamet ,  Johanne Tremblay ,  Ondrej Seda ,  Stephen Macmahon ,  John Chalmers

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/172

摘要： The invention provides with methods for characterizing and selecting, within a population of subjects with type-2 diabetes, subjects that are suited for clinical trials based on the identification of one or more genetic features, which are single nucleotide polymorphisms (SNPs), short tandem repeats (STRs), and/or other genomic markers. The invention further involves characterizing these subjects based on the probability of developing complications related to type-2 diabetes, such as, myocardial infarction, stroke and albuminuria. Also described are combinations and kits for carrying out the above-described methods.

摘要翻译： 本发明提供了在基于识别一个或多个遗传特征的单体核苷酸多态性（SNP），短串联 重复（STR）和/或其他基因组标记。 本发明还涉及基于与2型糖尿病相关的并发症的可能性，例如心肌梗塞，中风和白蛋白尿来表征这些受试者。 还描述了用于实施上述方法的组合和试剂盒。

公开(公告)号：US20120065075A1

公开(公告)日：2012-03-15

申请号：US13176623

申请日：2011-07-05

申请人： Pavel Hamet ,  Johanne Tremblay ,  Jacques De Champlain ,  François de Champlain ,  Josée Beaudet ,  Bernard de Champlain ,  Réginald Nadeau ,  Pierre Larochelle ,  John Chalmers ,  Stephen Macmahon

发明人： Pavel Hamet ,  Johanne Tremblay ,  Jacques De Champlain ,  François de Champlain ,  Josée Beaudet ,  Bernard de Champlain ,  Réginald Nadeau ,  Pierre Larochelle ,  John Chalmers ,  Stephen Macmahon

IPC分类号： C40B20/00 ,  C12Q1/68 ,  G01N33/53

CPC分类号： C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/172 ,  G01N33/6887 ,  G01N2333/58 ,  G01N2800/326

摘要： The present invention concerns a method of determining a predisposition to atrial fibrillation (AF) in a subject comprising: determining the presence of at least one copy of a risk allele from at least one polymorphic marker in a sample from the subject, wherein the presence of at least one copy of the risk allele is indicative of a predisposition to AF, and wherein said at least one polymorphic marker is: a) rs4674485; b) rs1466560; c) rs1880039; d) rs3849387; e) rs7039; f) rs2952860; g) rs9312515; h) rs1897527; i) rs2299277; j) rs2418828; k) rs2385833; l) rs6717960; m) rs10510266; or n) a substitute polymorphic marker in linkage disequilibrium with any one of the polymorphic markers of a) to m). Also described are kits for determining a predisposition to atrial fibrillation (AF).

摘要翻译： 本发明涉及确定受试者心房颤动（AF）倾向性的方法，其包括：确定来自受试者的样品中至少一个多态型标志物的风险等位基因的至少一个拷贝的存在，其中存在 风险等位基因的至少一个拷贝指示AF的倾向，并且其中所述至少一个多态性标记是：a）rs4674485; b）rs1466560; c）rs1880039; d）rs3849387; e）rs7039; f）rs2952860; g）rs9312515; h）rs1897527; i）rs2299277; j）rs2418828; k）rs2385833; l）rs6717960; m）rs10510266; 或n）与a）至m）中的任一个多态性标记连锁不平衡的替代多态性标记。 还描述了用于确定心房颤动（AF）倾向的试剂盒。

公开(公告)号：US5326551A

公开(公告)日：1994-07-05

申请号：US634220

申请日：1991-02-05

申请人： Pavel Hamet ,  Johanne Tremblay ,  Raymond Lamberet ,  Jean Leveille

发明人： Pavel Hamet ,  Johanne Tremblay ,  Raymond Lamberet ,  Jean Leveille

IPC分类号： A61K51/08 ,  A61K49/02

CPC分类号： A61K51/08 ,  A61K2123/00

摘要： Uptake, binding, and/or displacement of atrial natriuretic factor in a target organ of a mammal can be quantified by nuclear imaging. A diagnostically effective amount of a radio-labelled mammalian atrial natriuretic factor, active fragment or analog thereof is administered to a live mammal, and the live mammal or a portion thereof is subsequently imaged at one or more time intervals using a suitable radio-detecting device to quantify the uptake, binding and/or displacement of the radio-labelled atrial natriuretic factor, fragment or analog in one or more target organs.

摘要翻译： PCT No.PCT / CA90 / 00192 Sec。 371日期：1991年2月5日 102（e）日期1991年2月5日PCT Filed 1990年6月8日PCT公布。 第WO90 / 14845号公报 1990年12月13日。哺乳动物靶器官中心房钠尿因子的摄取，结合和/或置换可以通过核成像进行量化。 向活的哺乳动物施用诊断有效量的放射性标记的哺乳动物心房钠尿素因子，其活性片段或类似物，并且随后使用合适的放射线检测装置以一个或多个时间间隔对活的哺乳动物或其一部分进行成像 定量放射性标记的心房利钠因子，片段或类似物在一个或多个靶器官中的摄取，结合和/或置换。

公开(公告)号：US06699676B1

公开(公告)日：2004-03-02

申请号：US09586097

申请日：2000-06-02

申请人： Sergei N. Orlov ,  Pavel Hamet ,  Johanne Tremblay

发明人： Sergei N. Orlov ,  Pavel Hamet ,  Johanne Tremblay

IPC分类号： G01N33567

CPC分类号： A61K31/7048 ,  A61K31/704 ,  A61K31/7042

摘要： Longterm elevation of the intracellular Na+/K+ ratio inhibits macromolecule synthesis and proliferation in the majority of cell types studied so far, including vascular smooth muscle cells (VSMC). We report here that inhibition of the Na+,K+ pump in VSMC by ouabain or 1 hour preincubation in K+-depleted medium attenuated apoptosis triggered by serum withdrawal, staurosporine or okadaic acid. In the absence of ouabain, both DNA degradation and caspase-3 activation in VSMC undergoing apoptosis were insensitive to modification of the extracellular Na+/K+ ratio as well as to hyperosmotic cell shrinkage. In contrast, protection of VSMC from apoptosis by ouabain was abolished under equimolar substitution of Na+o with K+o, showing that the anti apoptotic action of Na+,K+ pump inhibition was caused by inversion of the intracellular Na+/K+ ratio. Unlike VSMC, the same level of increment of the [Na+]i/[K+]i ratio caused by 2 hours preincubation of Jurkat cells with ouabain did not affect chromatin cleavage and caspase-3 activity triggered by treatment with Fas ligand, staurosporine or hyperosmotic shrinkage. Thus, our results show for the first time that similarly to cell proliferation, maintenance of a physiologically low intracellular Na+/K+ ratio is required for progression of VSMC apoptosis.

摘要翻译： 细胞内Na + / K +比例的长期升高抑制了迄今为止研究的大多数细胞类型（包括血管平滑肌细胞（VSMC））的大分子合成和增殖。 我们在这里报告说，通过哇巴因在血管平滑肌细胞中抑制Na +，K +泵或在K +消耗性介质中1小时预孵育减少由血清戒断，星形孢菌素或冈田酸引起的细胞凋亡。 在没有哇巴因的情况下，经历凋亡的VSMC中的DNA降解和半胱天冬酶-3激活对细胞外Na + / K +比的改变以及高渗细胞收缩都不敏感。 相比之下，在K + O等摩尔Na +取代的情况下，哇巴因对VSMC的凋亡的保护被消除，表明Na +，K +泵抑制的抗凋亡作用是由反转引起的 的细胞内Na + / K +比。 与VSMC不同，Jurkat细胞与哇巴因预处理2小时引起的[Na +] i / [K +] i比例的增加水平不会影响染色质切割和由治疗引起的半胱天冬酶-3活性 Fas配体，星形孢菌素或高渗收缩。 因此，我们的研究结果首次表明，与细胞增殖类似，VSMC凋亡进展需要维持生理学上低的细胞内Na + / K +比。

公开(公告)号：US20080200414A1

公开(公告)日：2008-08-21

申请号：US11938894

申请日：2007-11-13

申请人： Johanne Tremblay ,  Pavel Hamet ,  Richard Lewanczuk ,  Francis Gossard ,  Nicolas Solban

发明人： Johanne Tremblay ,  Pavel Hamet ,  Richard Lewanczuk ,  Francis Gossard ,  Nicolas Solban

IPC分类号： A61K31/70 ,  C07H21/04 ,  C12N15/00 ,  C12N5/00 ,  C07K16/00 ,  C12P21/04

CPC分类号： C07K14/47 ,  A61K38/00 ,  A61K48/00

摘要： Novel nucleic acids and corresponding encoded proteins are described. Also described are corresponding recombinant vectors and host cells, as well as methods of producing the proteins. Also described are mimetics and antibodies to the proteins as well as compositions comprising the nucleic acid or proteins or a portion thereof. Methods and kits for the detection of a disease, disorder or abnormal physical state caused by abnormal modulation of calcium levels in a patient are also described. Methods for treating a patient having a disease, disorder or abnormal physical state caused by abnormal calcium levels are also described. Methods for assaying abnormal calcium levels are also described, as are methods for screening the efficacy of products for modulating abnormal calcium levels.

摘要翻译： 描述了新的核酸和相应的编码的蛋白质。 还描述了相应的重组载体和宿主细胞，以及产生蛋白质的方法。 还描述了模拟物和蛋白质的抗体以及包含核酸或蛋白质或其一部分的组合物。 还描述了用于检测由患者中钙水平的异常调节引起的疾病，病症或异常身体状态的方法和试剂盒。 还描述了治疗由异常钙水平引起的疾病，病症或异常身体状况的患者的方法。 还描述了测定异常钙水平的方法，以及用于筛选产物用于调节异常钙水平的功效的方法。

公开(公告)号：US20060127383A1

公开(公告)日：2006-06-15

申请号：US11347059

申请日：2006-02-02

申请人： Pavel Hamet ,  Johanne Tremblay ,  Christine Des Rosiers ,  Huifang Chen

发明人： Pavel Hamet ,  Johanne Tremblay ,  Christine Des Rosiers ,  Huifang Chen

IPC分类号： A61K35/14 ,  A61K33/00

CPC分类号： A61M1/3681 ,  A61M1/32 ,  A61M1/3683 ,  A61M1/3687 ,  A61M1/369 ,  A61M2202/0216 ,  A61M2205/053 ,  A61N2005/0661

摘要： Apoptosis and/or necrosis related disorders in the mammalian body, namely radiation exposure disorders, chemical exposure and ingestion disorders, neurological disorders and physical trauma disorders, are treated, and their onset is counteracted by preconditioning, by extracting from the mammalian body an aliquot of blood, subjecting the extracted aliquot, ex vivo, to an oxidative stressor such as exposure to ozone gas, a temperature stressor, i.e. temperatures above or below body temperatures, and ultraviolet light, and re-injecting the treated blood aliquot into the mammalian body. The treatment ha the effect of decreasing apoptosis/necrosis in the body, and of pre-conditioning the body better to withstand subsequently encountered apoptosis-inducing events.

摘要翻译： 治疗哺乳动物身体中的细​​胞凋亡和/或坏死相关疾病，即放射线暴露障碍，化学暴露和摄入障碍，神经障碍和身体创伤障碍，并通过预处理来抵消它们的发作，通过从哺乳动物体内提取等分试样 血液，将提取的等分试样离体处理到氧化应激源，例如暴露于臭氧气体，温度应激器，即高于或低于体温的温度和紫外线，并将经处理的血液等分试样重新注射到哺乳动物体内。 这种治疗方法是减少身体凋亡/坏死的作用，并且更好地预处理身体，以抵御随后遇到的凋亡诱导事件。