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    Diagnostic test for alzheimers disease
    1.
    发明授权
    Diagnostic test for alzheimers disease 失效
    阿尔茨海默病诊断试验

    公开(公告)号：US6107050A

    公开(公告)日：2000-08-22

    申请号：US075725

    申请日：1998-05-11

    申请人： Daniel L. Alkon ,  Antonelle R. Favit ,  Maurizio Grimaldi

    发明人： Daniel L. Alkon ,  Antonelle R. Favit ,  Maurizio Grimaldi

    IPC分类号： C07K14/47 ,  C07K16/18 ,  G01N33/50 ,  G01N33/573 ,  G01N33/68

    CPC分类号： C07K14/4711 ,  C07K16/18 ,  G01N33/5091 ,  G01N33/573 ,  G01N33/6872 ,  G01N33/6896 ,  G01N2333/9121 ,  G01N2800/2821 ,  Y10S436/811

    摘要： The present invention provides methods for the diagnosis of Alzheimer's disease using human cells. Specifically, one method detects differences between potassium channels in cells from Alzheimer's patient and normal donors, and differences in intracellular calcium concentrations between Alzheimer's and normal cells in response to chemicals known to increase intracellular calcium levels. Other methods detect differences between the memory associated GTP binding Cp20 protein levels between Alzheimer's and normal cells. Another method utilizes the differential effects of .beta.-amyloid protein on levels of the protein kinase C isoenzymes PKC.alpha. and PKC.gamma. in Alzheimer's and normal cells. Yet another method detects Eu-TTA fluorescence differences between Alzheimer's and normal cells treated with an activator of a receptor-mediated metabolic pathway. In addition a diagnostic index for improved assessment between Alzheimer's and non Alzheimer's cells is provided.

    摘要翻译： 本发明提供了使用人类细胞诊断阿尔茨海默病的方法。 具体来说，一种方法检测来自阿尔茨海默病患者和正常供体的细胞中的钾通道之间的差异，以及响应于已知增加细胞内钙水平的化学物质的阿尔茨海默氏病和正常细胞之间的细胞内钙浓度的差异。 其他方法检测与老年痴呆和正常细胞之间记忆相关的GTP结合Cp20蛋白水平之间的差异。 另一种方法利用β-淀粉样蛋白对阿尔茨海默氏症和正常细胞中蛋白激酶C同功酶PKCα和PKCγ水平的差异作用。 另一种方法检测阿尔茨海默氏症与用受体介导的代谢途径的激活剂治疗的正常细胞之间的Eu-TTA荧光差异。 此外，提供了用于改善阿尔茨海默氏症和非阿尔茨海默病细胞之间评估的诊断指标。

    Abnormalities of Phosphatase 2A (PP2A) for Diagnosis and Treatment of Alzheimer's Disease
    4.
    发明申请
    Abnormalities of Phosphatase 2A (PP2A) for Diagnosis and Treatment of Alzheimer's Disease 审中-公开
    磷酸酶2A（PP2A）用于阿尔茨海默病诊断和治疗的异常

    公开(公告)号：US20090029355A1

    公开(公告)日：2009-01-29

    申请号：US11660868

    申请日：2004-11-15

    申请人： Wei-Qin Zhao ,  Daniel L. Alkon

    发明人： Wei-Qin Zhao ,  Daniel L. Alkon

    IPC分类号： C12Q1/68 ,  C12Q1/42 ,  G01N33/53 ,  C07K16/00

    CPC分类号： C12Q1/6883 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/6896

    摘要： This invention relates to methods of diagnosing Alzheimer's disease and methods of screening for compounds for the treatment or prevention of Alzheimer's disease. The methods are based upon newly discovered differences in protein phosphatase 2A (PP2A) function and related molecular events in Alzheimer's disease cells compared to control cells. In one embodiment, differences in basal PP2A gene expression in Alzheimer's cells are compared to controls. In another embodiment differences in PP2A protein and enzyme activity are compared in test and control cells. In another embodiment differences in response to substances that inhibit PP2A function are compared. Still another embodiment detects differences in the subcellular distribution of phosphorylated Erk1/2, a substrate of PP2A, in normal and Alzheimer's disease cells. The detection of Alzheimer's disease-specific differences in PP2A function and related events in peripheral tissues provides the basis for highly practical and efficient tests and diagnostic test kits for the early diagnosis of Alzheimer's disease, as well as providing a biochemical basis for identifying therapeutic targets for drug development.

    摘要翻译： 本发明涉及诊断阿尔茨海默病的方法和筛选用于治疗或预防阿尔茨海默病的化合物的方法。 该方法基于新发现的蛋白磷酸酶2A（PP2A）功能和阿尔茨海默病细胞相关分子事件与对照细胞相比的差异。 在一个实施方案中，将阿尔茨海默氏病细胞中基础PP2A基因表达的差异与对照进行比较。 在另一个实施方案中，在测试和对照细胞中比较了PP2A蛋白质和酶活性的差异。 在另一个实施方案中，比较了抑制PP2A功能的物质的反应差异。 另一个实施方案检测正常和阿尔茨海默氏病细胞中磷酸化Erk1 / 2（PP2A底物）的亚细胞分布的差异。 检测外周组织中PP2A功能和相关事件中的阿尔茨海默病特异性差异为高龄实用和有效的测试和诊断试剂盒提供了基础，用于早期诊断阿尔茨海默氏病，并为确定治疗靶点提供了生物化学依据 药物开发。

    Dynamically stable associative learning neural system
    5.
    发明授权
    Dynamically stable associative learning neural system 失效
    动态稳定关联学习神经系统

    公开(公告)号：US5402522A

    公开(公告)日：1995-03-28

    申请号：US80860

    申请日：1993-06-22

    申请人： Daniel L. Alkon ,  Thomas P. Vogl ,  Kim L. Blackwell

    发明人： Daniel L. Alkon ,  Thomas P. Vogl ,  Kim L. Blackwell

    IPC分类号： G06N3/04 ,  G06F15/18

    CPC分类号： G06N3/04

    摘要： A dynamically stable associative learning neural network system include a plurality of synapses (122,22-28), a non-linear function circuit (30) and an adaptive weight circuit (150) for adjusting the weight of each synapse based upon the present signal and the prior history of signals applied to the input of the particular synapse and the present signal and the prior history of signals applied to the input of a predetermined set of other synapses. An embodiment of a conditional-signal neuron circuit (100) receives input signals from conditional stimuli and an unconditional-signal neuron circuit (110) receives input signals from unconditional stimuli. A neural network (200) is formed by a set of conditional-signal and unconditional-signal neuron circuits connected by flow-through synapses to form separate paths between each input (215) and a corresponding output (245). In one embodiment, the neural network (200) is initialized by varying the weight of the input signals from conditional stimuli, until a dynamic equilibrium is reached.

    摘要翻译： 动态稳定的关联学习神经网络系统包括多个突触（122,22-28），非线性函数电路（30）和自适应加权电路（150），用于根据本信号调整每个突触的重量 以及施加到特定突触的输入的信号的先前历史和当前信号以及施加到预定的其它突触组的输入的信号的先前历史。 条件信号神经元电路（100）的实施例从条件刺激接收输入信号，无条件信号神经元电路（110）从无条件刺激接收输入信号。 神经网络（200）由一组通过流通突触连接的条件信号和无条件信号神经元电路形成，以在每个输入（215）和相应的输出（245）之间形成分离的路径。 在一个实施例中，通过改变来自条件刺激的输入信号的权重来初始化神经网络（200），直到达到动态平衡。

    PKC activators and anticoagulant in regimen for treating stroke
    8.
    发明授权
    PKC activators and anticoagulant in regimen for treating stroke 有权
    PKC激活剂和治疗中风的方案中的抗凝血剂

    公开(公告)号：US09107890B2

    公开(公告)日：2015-08-18

    申请号：US13178843

    申请日：2011-07-08

    申请人： Daniel L. Alkon

    发明人： Daniel L. Alkon

    IPC分类号： A61K49/00 ,  A61K31/20 ,  A61K31/366 ,  A61K38/49

    CPC分类号： A61K38/49 ,  A61K9/0019 ,  A61K31/20 ,  A61K31/366 ,  C12Y304/21068 ,  A61K2300/00

    摘要： The present disclosure provides a method for treating stroke by administering to a subject an anticoagulant, e.g., recombinant tissue plasminogen activator (rTPA), and a protein kinase C (PKC) activator followed by administration of at least one PKC activator for a duration of treatment. The methods disclosed herein may limit the size of infarction and/or reduce mortality, the disruption of the blood-brain barrier, and/or the hemorrhagic damage due to ischemic stroke compared with rTPA administration alone; and may also extend the therapeutic time window for administering rTPA after a stroke. Also disclosed are kits comprising rTPA and a PKC activator for treating stroke.

    摘要翻译： 本公开提供了通过向受试者施用抗凝血剂（例如重组组织纤溶酶原激活物（rTPA））和蛋白激酶C（PKC）激活剂，随后施用至少一种PKC活化剂持续治疗的方法来治疗中风的方法 。 与单独的rTPA给药相比，本文公开的方法可以限制梗塞的大小和/或降低死亡率，血脑屏障的破坏和/或由于缺血性卒中引起的出血性损伤; 并且还可以延长在卒中后施用rTPA的治疗时间窗口。 还公开了包含rTPA和用于治疗中风的PKC激活剂的试剂盒。

    FATTY ACID PROTEIN KINASE C ACTIVATORS AND ANTICOAGULANT FOR THE TREATMENT OF STROKE
    9.
    发明申请
    FATTY ACID PROTEIN KINASE C ACTIVATORS AND ANTICOAGULANT FOR THE TREATMENT OF STROKE 审中-公开
    脂肪酸蛋白激酶C激活剂和抗凝剂治疗肌腱

    公开(公告)号：US20120027687A1

    公开(公告)日：2012-02-02

    申请号：US13178835

    申请日：2011-07-08

    申请人： Daniel L. Alkon

    发明人： Daniel L. Alkon

    IPC分类号： A61K49/04 ,  A61P9/10 ,  A61P7/02 ,  A61K38/49

    CPC分类号： A61K38/49 ,  A61K9/0019 ,  A61K31/20 ,  A61K31/366 ,  C12Y304/21068 ,  A61K2300/00

    摘要： The present disclosure provides a method for treating stroke by administering an anticoagulant, e.g., recombinant tissue plasminogen activator (rTPA), and a protein kinase C(PKC) activator, wherein the PKC activator may be administered before, after, or at the same time as the rTPA. The methods disclosed herein may limit the size of infarction and/or reduce mortality, the disruption of the blood-brain barrier, and/or the hemorrhagic damage due to ischemic stroke compared with rTPA administration alone; and may also extend the therapeutic time window for administering rTPA after a stroke. Also disclosed are compositions and kits comprising rTPA and a PKC activator for treating stroke.

    摘要翻译： 本公开提供了一种通过施用抗凝血剂（例如重组组织纤溶酶原激活物（rTPA））和蛋白激酶C（PKC）激活剂来治疗中风的方法，其中PKC激活剂可以在之前，之后或同时施用 作为rTPA。 与单独的rTPA给药相比，本文公开的方法可以限制梗塞的大小和/或降低死亡率，血脑屏障的破坏和/或由于缺血性卒中引起的出血性损伤; 并且还可以延长在卒中后施用rTPA的治疗时间窗口。 还公开了包含用于治疗中风的rTPA和PKC激活剂的组合物和试剂盒。