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    Animal model for detection of vulnerable plaques
    1.
    发明授权
    Animal model for detection of vulnerable plaques 失效
    用于检测脆弱斑块的动物模型

    公开(公告)号：US06580016B2

    公开(公告)日：2003-06-17

    申请号：US09760182

    申请日：2001-01-12

    申请人： Paul S. Teirstein ,  Kenneth W. Carpenter ,  Istvan Szinai ,  David A. Schwartz

    发明人： Paul S. Teirstein ,  Kenneth W. Carpenter ,  Istvan Szinai ,  David A. Schwartz

    IPC分类号： A01K6700

    CPC分类号： A61K49/126 ,  A61B6/4057 ,  A61B6/481 ,  A61B6/508 ,  A61K49/0442 ,  A61K49/085 ,  A61K51/065 ,  G01N33/92 ,  G01N2400/40 ,  G01N2800/323

    摘要： The present invention provides in vivo methods for detection of vulnerable plaque in a subject in need thereof. In the invention method the subject is administered a diagnostic amount of a biologically compatible detectable lipid-avid agent, the detectable lipid-avid agent is allowed to penetrate arterial walls and attach to any lipid accumulations of oxidized LDL-cholesterol in arterial walls in the wall of an artery; unbound detectable lipid-avid agent is allowed to clear from the body by natural processes, and the presence of the detectable lipid-avid agent attached to the lipid accumulation in the wall of the artery is detected. Detection of bound lipid-avid agent indicates the presence of a vulnerable plaque and predicts a heightened risk of lethal heart attack or thrombus. The detectable lipid-avid agent is selected for its ability to penetrate arterial walls and bind with oxidized LDL-cholesterol in the lipid accumulation in a vulnerable plaque. Alternatively, macrophage-avid agents, for example a lipid-avid agent attached to a macrophage-specific antibody, can be used in the invention methods. The invention further includes methods for in vitro assays for detecting vulnerable plaque and a porcine animal model of vulnerable plaque useful for testing treatment modalities.

    摘要翻译： 本发明提供了在有需要的受试者中检测易损斑块的体内方法。 在本发明方法中，给予受试者诊断量的生物相容性可检测的脂质 - 抗体试剂，允许可检测的脂质激动剂渗透动脉壁并附着于壁中动脉壁中氧化的LDL-胆固醇的任何脂质积聚 的动脉 通过天然过程使未结合的可检测的脂质 - 抗体试剂从身体中清除，并且检测附着在动脉壁中的脂质积聚的可检测的脂质激动剂的存在。 检测结合的脂质抗体剂表明存在易受伤害的斑块，并预测致死性心脏病发作或血栓的风险增加。 选择可检测的脂质抗体试剂，以其穿透动脉壁并与氧化的LDL-胆固醇结合在易损斑块中的脂质积聚中。 或者，巨噬细胞激动剂，例如与巨噬细胞特异性抗体连接的脂质 - 抗体试剂可用于本发明的方法中。 本发明还包括用于检测易损斑块的体外测定方法和用于测试治疗方式的易损斑块的猪动物模型。

    Perlecan transgenic animals and methods of identifying compounds for the treatment of amyloidoses
    2.
    发明授权
    Perlecan transgenic animals and methods of identifying compounds for the treatment of amyloidoses 有权
    Perlecan转基因动物和鉴定用于治疗淀粉样变性的化合物的方法

    公开(公告)号：US06563016B1

    公开(公告)日：2003-05-13

    申请号：US09536231

    申请日：2000-03-27

    申请人： Alan D. Snow ,  Ken-Ichiro Fukuchi ,  John Hassell

    发明人： Alan D. Snow ,  Ken-Ichiro Fukuchi ,  John Hassell

    IPC分类号： A01K6700

    CPC分类号： C12N15/8509 ,  A01K67/0275 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/0306 ,  A01K2267/0312 ,  A01K2267/0318 ,  A01K2267/0356 ,  A01K2267/0362 ,  A61K49/0008 ,  C07K14/4711 ,  C12N2800/108 ,  C12N2830/008

    摘要： The invention provides a transgenic non-human animal expressing a perlecan encoding transgene. Also provided is a double-transgenic non-human animal expressing a perlecan and a amyloid encoding transgene. A method of screening for a compound which alters the rate or extent of amyloid deposition is additionally provided. The method consists of: (a) constructing a perlecan transgenic animal; (b) administering an effective amount of a test compound to said perlecan transgenic animal; and (c) determining whether said test compound alters the extent or rate of amyloid deposition. Finally, the invention provides a method of screening for a compound which alters the rate or extent of amyloid deposition. The method consists of: (a) constructing a perlecan/amyloid double-transgenic animal; (b) administering an effective amount of a test compound to said perlecan/amyloid double-transgenic animal; and (c) determining whether said test compound alters the extent or rate of amyloid deposition.

    摘要翻译： 本发明提供了表达编码转基因的全基因组的转基因非人动物。 还提供了表达perlecan和编码转基因淀粉样蛋白的双转基因非人动物。 另外提供筛选改变淀粉样蛋白沉积速度或程度的化合物的方法。 该方法包括：（a）构建一个全基因组转基因动物; （b）向所述perlecan转基因动物施用有效量的测试化合物; 和（c）确定所述测试化合物是否改变淀粉样蛋白沉积的程度或速率。 最后，本发明提供了筛选改变淀粉样蛋白沉积速度或程度的化合物的方法。 该方法包括：（a）构建一个perlecan /淀粉样蛋白双转基因动物; （b）向所述perlecan /淀粉样蛋白双转基因动物施用有效量的测试化合物; 和（c）确定所述测试化合物是否改变淀粉样蛋白沉积的程度或速率。

    Propagation of human hepatocytes in non-human mammals
    3.
    发明授权
    Propagation of human hepatocytes in non-human mammals 失效
    人类肝细胞在非人哺乳动物中的繁殖

    公开(公告)号：US06525242B1

    公开(公告)日：2003-02-25

    申请号：US09431901

    申请日：1999-11-02

    申请人： George Y. Wu ,  Catherine H Wu

    发明人： George Y. Wu ,  Catherine H Wu

    IPC分类号： A01K6700

    CPC分类号： C12N15/113 ,  A01K67/0271 ,  A01K2217/05 ,  A61K39/001 ,  A61K2035/122 ,  C12N5/067 ,  C12N9/1247 ,  C12N9/6462 ,  C12Y304/21073 ,  G01N2333/02 ,  G01N2333/18 ,  Y02A50/388 ,  Y02A50/412

    摘要： The present invention relates to the preparation of non-human animals having chimeric livers, whereby some or substantially all of the hepatocytes present are human hepatocytes. It is based, at least in part, on the discovery that rats, tolerized in utero against human hepatocytes, were found to serve as long-term hosts for human hepatocytes introduced post-natally, and the introduced hepatocytes maintained their differentiated phenotype, as evidenced by continued production of human albumin.

    摘要翻译： 本发明涉及具有嵌合肝脏的非人动物的制备，其中存在的一些或基本上全部的肝细胞是人肝细胞。 它至少部分地基于以下发现：发现在子宫内耐受人类肝细胞的大鼠被认为是在天后引入的人肝细胞的长期宿主，引入的肝细胞保持其分化表型，如 通过持续生产人体白蛋白。

    Method for preparing entomopathogenic nematodes for storage by mixing with non-fibrous cellulose particles of less than 300 &mgr;M
    4.
    发明授权
    Method for preparing entomopathogenic nematodes for storage by mixing with non-fibrous cellulose particles of less than 300 &mgr;M 失效
    用于通过与小于300μm的非纤维状纤维素颗粒混合来制备昆虫病原线虫的方法

    公开(公告)号：US06407310B1

    公开(公告)日：2002-06-18

    申请号：US09806143

    申请日：2001-03-28

    申请人： Robin Anthony Bedding ,  Simone Daniela Clark ,  Michael James Lacey ,  Karen Louise Butler

    发明人： Robin Anthony Bedding ,  Simone Daniela Clark ,  Michael James Lacey ,  Karen Louise Butler

    IPC分类号： A01K6700

    CPC分类号： A01K67/033 ,  A01N63/00 ,  A01N25/34 ,  A01N2300/00

    摘要： Third stage juvenile (J3) entomopathogenic nematodes are prepared for storage by being induced into a state of cryptobiosis. The induction of cryptobiosis is effected by mixing an aqueous cream of the J3 nematodes with anhydrous, small particles (average maximum dimension less than 300 &mgr;m) of non-fibrous cellulose. The proportions of the aqueous cream and non-fibrous cellulose particles are such that, after equilibration, the mixture has a water activity in the range 0.80 to 0.995. Preferably an anti-fungal agent is included in the aqueous cream. To store the cryptobiotic J3 nematodes, the mixture is preferably kept in a container, fitted with an attachment which maintains the water activity in the container at a required value. The attachment includes a rigid tube that connects the interior of the container with a chamber that is vented to ambient atmosphere by small apparatus. When in use the chamber contains water-absorbent material saturated with water or with a saturated salt solution, and the tube contains an air-permeable plug. An alternative attachment comprises a plastic envelope, one face of which is stuck to the wall of the container. Small apertures in the face are aligned with apertures in the container wall. Small apertures in the other face connect the inside of the envelope to ambient atmosphere. In use, the envelope contains a water-absorbent material saturated with water or a salt solution, and at least one spacer member.

    摘要翻译： 制备第三阶段幼虫（J3）昆虫病原线虫，通过诱导进入隐孢子虫病状进行储存。 通过将J3线虫的水性乳膏与非纤维状纤维素的无水，小颗粒（平均最大尺寸小于300μm）混合来实现致密生物的诱导。 水性乳液和非纤维状纤维素颗粒的比例使得在平衡后，该混合物的水分活度在0.80-0.995的范围内。 优选地，水性乳膏中包含抗真菌剂。 为了储存密生生物J3线虫，优选将混合物保存在容器中，该容器装有将容器中的水活性保持在所需值的附件。 附件包括刚性管，其将容器的内部与通过小型设备排放到周围环境的室相连。 当使用时，该室含有被水或饱和盐溶液饱和的吸水材料，并且该管含有透气性的塞子。 替代附件包括塑料封套，其一面贴在容器的壁上。 面中的小孔与容器壁中的孔对齐。 另一面的小孔将信封的内部连接到环境大气。 在使用中，信封包含饱和水或盐溶液的吸水材料和至少一个间隔件。

    Transgenic mouse model of alzheimer's disease and cerebral amyloid angiopathy
    7.
    发明授权
    Transgenic mouse model of alzheimer's disease and cerebral amyloid angiopathy 失效
    阿尔茨海默病和脑淀粉样血管病的转基因小鼠模型

    公开(公告)号：US06175057B1

    公开(公告)日：2001-01-16

    申请号：US08947295

    申请日：1997-10-08

    申请人： Lennart Mucke ,  Tony Wyss-Coray ,  Eliezer Masliah

    发明人： Lennart Mucke ,  Tony Wyss-Coray ,  Eliezer Masliah

    IPC分类号： A01K6700

    CPC分类号： C12N15/8509 ,  A01K67/0275 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/0312 ,  A01K2267/0318 ,  C12N2830/008

    摘要： The present invention features non-human transgenic animal models for Alzheimer's disease (AD) and CAA, wherein the transgenic animal is characterized by 1) overexpression of bioactive transforming growth factor-&bgr;1 (TGF-&bgr;1) or 2) both overexpression of bioactive TGF-&bgr;1 and expression of a human amyloid &bgr; precursor protein (APP) gene product. The transgenic animals may be either homozygous or heterozygous for these alterations. Bigenic animals are further characterized by development of AD-associated and/or CAA-associated pathology within about two to three months of age.

    摘要翻译： 本发明的特征在于用于阿尔茨海默氏病（AD）和CAA的非人转基因动物模型，其中转基因动物的特征在于1）生物活性转化生长因子-β1（TGF-β1）的过度表达或2）生物活性TGF- β1和人淀粉样蛋白β前体蛋白（APP）基因产物的表达。 对于这些改变，转基因动物可以是纯合的或杂合的。 本发型动物的进一步特征在于在约2-3个月龄内发展AD相关和/或CAA相关的病理学。

    Transgenic mice expressing human p25
    10.
    发明授权
    Transgenic mice expressing human p25 失效
    表达人p25的转基因小鼠

    公开(公告)号：US06693226B1

    公开(公告)日：2004-02-17

    申请号：US09496445

    申请日：2000-02-02

    申请人： John D. McNeish ,  Michael K. Ahlijanian

    发明人： John D. McNeish ,  Michael K. Ahlijanian

    IPC分类号： A01K6700

    CPC分类号： A01K67/0275 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/0312 ,  A01K2267/0318 ,  C07K14/4738 ,  C12N15/8509 ,  C12N2830/008

    摘要： The invention provides transgenic, non-human animals and transgenic non-human mammalian cells harboring a transgene encoding a p25 (activator of the protein kinase cdk 5) polypeptide. The two neuropathological lesions associated with Alzheimer's disease (AD) are amyloid plaques and neurofibrillary tangles (NFTs), composed predominantly of amyloid &bgr; peptides and hyperphosphorylated tau, respectvely. While animal models for plaque formation exist, there is no animal model that recapitulates the formation of NFTs. This invention provides transgenic mice that overexpress human p25, an activator of cdk5, resulting in tau that is hyperphosphorylated at AD-relevant epitopes. Deposition of tau is detected in the amygdala, thalamus and cortex. Increased phosphorylated neurofilament, silver-positive neurons and neuronal death are also observed in these regions. We conclude that the overexpression of p25, an activator of cdk5, is sufficient to produce hyperphosphorylation of tau and neuronal death. The p25 transgenic mouse represents the first model for tau pathology in AD.

    摘要翻译： 本发明提供具有编码p25（蛋白激酶cdk 5的活化剂）多肽的转基因的转基因非人动物和转基因非人哺乳动物细胞。 与阿尔茨海默病（AD）相关的两种神经病理学病变是淀粉样斑块和神经原纤维缠结（NFTs），主要由淀粉样β肽组成，超磷酸化tau。 虽然存在斑块形成的动物模型，但没有重现NFT形成的动物模型。 本发明提供过表达人p25的转基因小鼠，其是cdk5的激活剂，导致在AD相关表位处被过度磷酸化的tau。 在杏仁核，丘脑和皮质中检测到tau的沉积。 在这些区域也观察到增加的磷酸化神经丝，银阳性神经元和神经元死亡。 我们得出结论，cd25的激活剂p25的过度表达足以产生tau和神经元死亡的高度磷酸化。 p25转基因小鼠代表AD中tau病理学的第一个模型。