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    Peptides to overcome inhibition of nerve growth
    2.
    发明授权
    Peptides to overcome inhibition of nerve growth 失效
    克服抑制神经生长的肽

    公开(公告)号：US5543498A

    公开(公告)日：1996-08-06

    申请号：US417279

    申请日：1995-04-05

    申请人： Mark C. Fishman ,  Michihiro Igarashi ,  Stephen M. Strittmatter

    发明人： Mark C. Fishman ,  Michihiro Igarashi ,  Stephen M. Strittmatter

    IPC分类号： A61K38/00 ,  C07K14/47 ,  A61K38/04 ,  C07K7/06

    CPC分类号： C07K14/4702 ,  A61K38/00

    摘要： Inhibition of nerve growth normally helps to prevent aberrant pathway or target selection, but also prevents needed regeneration in the mammalian central nervous system. The responsible inhibitory ligands are unknown, but pertussis toxin-sensitive G proteins, which are enriched in growth cones, appear to be involved in causing the responding growth cones to collapse. GAP-43 is an intracellular protein that can amplify the response to the stimulation of G protein-coupled receptors. We have attempted to modify the sensitivity of nerves to inhibitory signals by the use of GAP-43 peptides. The peptide corresponding to the native amino terminus sequence stimulates G.sub.o and enhances the growth cone collapse induced by inhibitory ligands. Modification of two critical cysteines generates peptides which inhibit G.sub.o and which markedly reduce the degree of inhibitor-mediated growth cone collapse.

    摘要翻译： 抑制神经生长通常有助于防止异常途径或靶标选择，而且可以防止哺乳动物中枢神经系统中需要的再生。 负责的抑制性配体是未知的，但是富含生长锥的百日咳毒素敏感的G蛋白似乎涉及引起响应的生长锥体崩溃。 GAP-43是可以扩增对G蛋白偶联受体刺激反应的细胞内蛋白质。 我们试图通过使用GAP-43肽来改变神经对抑制性信号的敏感性。 对应于天然氨基末端序列的肽刺激Go，并增强由抑制性配体诱导的生长锥塌陷。 两个关键半胱氨酸的修饰产生抑制Go的肽，并显着降低抑制剂介导的生长锥体崩溃的程度。

    Endothelial NOS transgenic animals and methods of use
    8.
    发明授权
    Endothelial NOS transgenic animals and methods of use 失效
    内皮型NOS转基因动物及其使用方法

    公开(公告)号：US06630347B1

    公开(公告)日：2003-10-07

    申请号：US09692056

    申请日：2000-10-20

    申请人： Paul L. Huang ,  Mark C. Fishman ,  Michael A. Moskowitz

    发明人： Paul L. Huang ,  Mark C. Fishman ,  Michael A. Moskowitz

    IPC分类号： C12N500

    CPC分类号： C12N15/8509 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0375 ,  C12N9/0075 ,  C12N9/0077

    摘要： This invention relates to transgenic non-human animals comprising a disrupted endothelial nitric oxide synthase gene. These animals exhibit abnormal wound-healing properties and hypertension. This invention also relates to methods of using the transgenic animals to screen for compounds having a potential therapeutic utility for vascular endothelial disorders, such as hypertension, cerebral ischemia or stroke, atherosclerosis and wound-healing activities. Moreover, this invention also relates to methods of treating a patient suffering from hypertension and wound-healing abnormalities with the compounds identified using the transgenic animals, and methods of making the transgenic animals. A method of treating a wound using nitroglycerin is also provided.

    摘要翻译： 本发明涉及包含破坏的内皮一氧化氮合酶基因的转基因非人动物。 这些动物表现出异常的伤口愈合特性和高血压。 本发明还涉及使用转基因动物筛选具有血管内皮疾病（例如高血压，脑缺血或中风），动脉粥样硬化和伤口愈合活性的潜在治疗效用的化合物的方法。 此外，本发明还涉及使用转基因动物鉴定的化合物治疗患有高血压和伤口愈合异常的患者的方法，以及制备转基因动物的方法。 还提供了使用硝酸甘油治疗伤口的方法。

    Endothelial NOS knockout mice and methods of use
    10.
    发明授权
    Endothelial NOS knockout mice and methods of use 失效
    内皮NOS敲除小鼠及使用方法

    公开(公告)号：US06310270B1

    公开(公告)日：2001-10-30

    申请号：US08818082

    申请日：1997-03-14

    申请人： Paul L. Huang ,  Mark C. Fishman ,  Michael A. Moskowitz

    发明人： Paul L. Huang ,  Mark C. Fishman ,  Michael A. Moskowitz

    IPC分类号： A01K6700

    CPC分类号： C12N15/8509 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0375 ,  C12N9/0075 ,  C12N9/0077

    摘要： This invention relates to transgenic non-human animals comprising a disrupted endothelial nitric oxide synthase gene. These animals exhibit abnormal wound-healing properties and hypertension. This invention also relates to methods of using the transgenic animals to screen for compounds having a potential therapeutic utility for vascular endothelial disorders, such as hypertension, cerebral ischemia or stroke, atherosclerosis and wound-healing activities. Moreover, this invention also relates to methods of treating a patient suffering from hypertension and wound-healing abnormalities with the compounds identified using the transgenic animals, and methods of making the transgenic animals. A method of treating a wound using nitroglycerin is also provided.

    摘要翻译： 本发明涉及包含破坏的内皮一氧化氮合酶基因的转基因非人动物。 这些动物表现出异常的伤口愈合特性和高血压。 本发明还涉及使用转基因动物筛选具有血管内皮疾病（例如高血压，脑缺血或中风），动脉粥样硬化和伤口愈合活性的潜在治疗效用的化合物的方法。 此外，本发明还涉及使用转基因动物鉴定的化合物治疗患有高血压和伤口愈合异常的患者的方法，以及制备转基因动物的方法。 还提供了使用硝酸甘油治疗伤口的方法。