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92 条记录 (耗时 0.038 秒)

    Inhibition of retroviral LTR promoters by calcium response modifiers
    44.
    发明授权
    Inhibition of retroviral LTR promoters by calcium response modifiers 失效
    通过钙反应调节剂抑制逆转录病毒LTR启动子

    公开(公告)号：US6057346A

    公开(公告)日：2000-05-02

    申请号：US353765

    申请日：1994-12-12

    申请人： Elise C. Kohn ,  Lance A. Liotta ,  Kevin L. Gardner

    发明人： Elise C. Kohn ,  Lance A. Liotta ,  Kevin L. Gardner

    IPC分类号： A61K31/4174 ,  A61K31/4192 ,  A61K31/41 ,  A01N43/64

    CPC分类号： A61K31/4174 ,  A61K31/4192

    摘要： A class of calcium-response modification compounds is disclosed which inhibits the activation of retroviral LTR promoters, including the HIV-LTR. This class of compounds are used to delay or suppress the transition of a retroviral infection from a latent to a virulent condition, thereby ameliorating retrovirally caused diseases such as AIDS. The compounds are also useful in cancer treatment, allowing for coordinated therapeutic approaches to retroviral diseases and related cancers such as AIDS and Kaposi's Sarcoma. The compounds are also useful in standardizing in vitro assays of clinical and experimental importance.

    摘要翻译： 公开了一类钙响应修饰化合物，其抑制包括HIV-LTR在内的逆转录病毒LTR启动子的活化。 这类化合物用于延缓或抑制逆转录病毒感染从潜伏状态转变为有毒状态，从而改善逆转录病毒引起的疾病如艾滋病。 该化合物也可用于癌症治疗，允许对逆转录病毒疾病和相关癌症如AIDS和卡波西肉瘤的协调治疗方法。 该化合物还可用于标准化临床和实验重要性的体外测定。

    Light-emitting immunoassay
    45.
    发明授权
    Light-emitting immunoassay 失效
    发光免疫测定

    公开(公告)号：US5942407A

    公开(公告)日：1999-08-24

    申请号：US882594

    申请日：1997-06-25

    申请人： Lance A. Liotta ,  Bryan C. Christiansen ,  Alan R. Day ,  Tabitha Harlacher ,  Katherine Paweletz

    发明人： Lance A. Liotta ,  Bryan C. Christiansen ,  Alan R. Day ,  Tabitha Harlacher ,  Katherine Paweletz

    IPC分类号： G01N33/543 ,  G01N33/58 ,  C12Q1/28 ,  C12Q1/00 ,  G01N33/53

    CPC分类号： G01N33/582 ,  G01N33/54366

    摘要： A light generating dry disposable device for determining the presence of analytes in a test sample is disclosed. The device comprises a first zone containing conjugated ligand which is capable of reacting with analytes in the test sample. The ligand is conjugated with a photoprotein or related enzyme. The device further comprises a second trapping zone comprising immobilized analyte. The device also includes a third zone containing a reporter system that activates light generation by the conjugate. The conjugates are maintained in the first zone such that they are removable from the first zone when reacted with the soluble analytes from the test sample passing through the first zone, but not removed from the second trapping zone in the absence of such analytes. The third zone contains material capable of reacting with the photoprotein- or enzyme-linked ligand to produce a light-emitting reaction which indicates the presence of the analyte being tested. The present invention provides dry flow through zones. The trapping zone is juxtaposed with the light activation zone such that only formed analyte conjugate complexes enter the light activation zone. Also disclosed is the use of a luminometer for measuring the amount of light generated from the assay device upon detection of analyte. Other provisions are disclosed for recording and quantifying the amount of analyte, such as for example, photographic film.

    摘要翻译： 公开了一种用于确定测试样品中分析物的存在的发光干燥一次性装置。 该装置包括含有共轭配体的第一区，其能够与测试样品中的分析物反应。 配体与光蛋白或相关酶缀合。 该装置还包括包含固定分析物的第二捕集区。 该装置还包括含有报告系统的第三区域，其通过缀合物激活光产生。 当共轭物与来自经过第一区的测试样品的可溶性分析物反应时，它们可以从第一区域移除，但在不存在这种分析物的情况下不从第二捕获区域移除。 第三区含有能够与光蛋白或酶连接的配体反应以产生发光反应的物质，其指示待测分析物的存在。 本发明提供干流穿过区域。 捕获区与光活化区并置，使得仅形成的分析物共轭复合物进入光活化区。 还公开了使用发光计来测量在检测分析物时由测定装置产生的光量。 公开了用于记录和定量分析物的量的其它规定，例如照相胶片。

    Matrix metalloproteinase inhibitor peptides
    47.
    发明授权
    Matrix metalloproteinase inhibitor peptides 失效
    基质金属蛋白酶抑制剂肽

    公开(公告)号：US5595885A

    公开(公告)日：1997-01-21

    申请号：US39525

    申请日：1993-03-29

    申请人： William G. Stetler-Stevenson ,  Lance A. Liotta ,  Henry C. Krutzsch

    发明人： William G. Stetler-Stevenson ,  Lance A. Liotta ,  Henry C. Krutzsch

    IPC分类号： A61K35/12 ,  A61K38/00 ,  A61K38/55 ,  A61K39/395 ,  A61K48/00 ,  A61K49/00 ,  A61P37/00 ,  C07K1/16 ,  C07K1/22 ,  C07K7/08 ,  C07K14/00 ,  C07K14/81 ,  C07K16/00 ,  C12N1/21 ,  C12N15/09 ,  C12N15/15 ,  C12P21/02 ,  C12R1/91 ,  G01N33/53 ,  G01N33/573 ,  C12N15/00

    CPC分类号： C07K14/8146 ,  A61K38/00

    摘要： The present invention is an isolated protein of 21,600 Da which binds to both latent and activated type IV collagenase with high affinity at 1:1 molar stoichiometry, thereby abolishing enzyme activity. The protein is purified by affinity chromatography on solid phase metalloproteinase, or solid phase metalloproteinase substrates which bind the enzyme-inhibitor complex. The complete primary structure of this protein (initially called CSC-21K), as determined by sequencing overlapping peptides spanning the entire protein, reveals homology with a protein called TIMP, Tissue Inhibitor of Metalloproteinases. In addition, a cDNA for this novel inhibitor, now designated TIMP-2, was cloned from a melanoma cell and its sequence was compared with that of human TIMP-1. Northern blots of melanoma cell mRNA showed two distinct transcripts of 0.9 kb and 3.5 kb which are down-regulated by transforming growth factor-.beta., and are unchanged by phorbol ester treatment. The inhibitor of the present invention may be used for treatment of pathologic conditions resulting from inappropriate degradation of extracellular matrix molecules by matrix metalloproteinases, such as metastatic neoplasia, myocardial infarction, and arthritis. Therapeutic treatments using this inhibitor may include formulations for inhalation and inclusion complexes adapted for buccal or sublingual administration, or administration of a recombinant DNA molecule which expresses a DNA segment that encodes the matrix metalloproteinase inhibitor of this invention.

    摘要翻译： 本发明是21,600Da的分离蛋白，其以1:1的摩尔化学计量比以高亲和力结合潜在和活化的IV型胶原酶，从而消除酶活性。 蛋白质通过固相金属蛋白酶上的亲和层析或结合酶抑制剂复合物的固相金属蛋白酶底物纯化。 通过测序跨越整个蛋白质的重叠肽测定，该蛋白质（最初称为CSC-21K）的完整的一级结构显示与称为TIMP，金属蛋白酶组织抑制剂的蛋白质的同源性。 此外，从黑素瘤细胞中克隆了此新型抑制剂cDNA（现称为TIMP-2），并将其序列与人TIMP-1进行比较。 黑色素瘤细胞mRNA的Northern印迹显示0.9kb和3.5kb的两个不同的转录物，其通过转化生长因子-β下调，并且通过佛波酯处理不变。 本发明的抑制剂可用于治疗由基质金属蛋白酶如转移性肿瘤，心肌梗塞和关节炎不适当地降解细胞外基质分子而导致的病理状况。 使用该抑制剂的治疗性治疗可以包括适于口腔或舌下施用的吸入制剂和包合配合物，或者给予表达编码本发明的基质金属蛋白酶抑制剂的DNA区段的重组DNA分子。

    Matrix metalloproteinase peptides: role in diagnosis and therapy
    50.
    发明授权
    Matrix metalloproteinase peptides: role in diagnosis and therapy 失效
    基质金属蛋白酶肽：在诊断和治疗中的作用

    公开(公告)号：US5280106A

    公开(公告)日：1994-01-18

    申请号：US488460

    申请日：1990-02-26

    申请人： Lance A. Liotta ,  William Stetler-Stevenson ,  Henry Krutzsch

    发明人： Lance A. Liotta ,  William Stetler-Stevenson ,  Henry Krutzsch

    IPC分类号： G01N33/53 ,  A61K9/08 ,  A61K38/55 ,  A61P19/02 ,  A61P35/00 ,  A61P43/00 ,  C07H21/04 ,  C07K7/06 ,  C07K7/08 ,  C07K14/00 ,  C07K14/81 ,  C07K16/00 ,  C07K16/38 ,  C07K17/00 ,  C12N5/10 ,  C12N9/99 ,  C12N15/09 ,  G01N33/573 ,  C07K13/00 ,  A61K39/00 ,  C12N9/50

    CPC分类号： C07K14/8146 ,  G01N33/573 ,  Y10S530/806 ,  Y10S530/81

    摘要： A family of metalloproteinases exist which cleave extracellular matrix molecules. These metalloproteinases are secreted in a latent inactive form and require activation in order to specifically cleave the preferred substrate. A series of peptides have been prepared based on the complete sequence analysis of type IV procollagenase. Peptide inhibitors were synthesized which correspond to cysteine repeat regions and histidine containing regions; the mechanism of action of these peptides involves inhibition of binding of the enzyme to the substrate. Peptide inhibitors were synthesized which correspond to the peptide cleaved off during activation, and constitute a novel class of metalloproteinase inhibitors. These inhibitors are members of a series of peptides which contain the core amino acid sequence RKPRC or analogs thereof. The cysteine residue is required for activity. Affinity purified antibodies directed against specific peptides can be used to a) detect any general metalloproteinase enzyme with the sequence in part VAAHE or PRCGNPD, and distinguish it from other known members of the metalloproteinase family, b) block functional domains resulting in the inhibition of enzyme activity, and c) distinguish latent from activated forms of the enzyme.

    摘要翻译： 存在切割细胞外基质分子的金属蛋白酶家族。 这些金属蛋白酶以潜伏活性形式分泌并需要活化以特异性切割优选的底物。 已经基于IV型原胶原酶的完整序列分析制备了一系列肽。 合成肽抑制剂，其对应于半胱氨酸重复区域和组氨酸区域; 这些肽的作用机理涉及抑制酶与底物的结合。 合成肽抑制剂，其对应于在活化期间切除的肽，并构成新型的金属蛋白酶抑制剂。 这些抑制剂是含有核心氨基酸序列RKPRC或其类似物的一系列肽的成员。 活性需要半胱氨酸残基。 针对特异性肽的亲和纯化抗体可用于a）用部分VAAHE或PRCGNPD中的序列检测任何一般金属蛋白酶，并将其与其他已知的金属蛋白酶家族成员区分开，b）阻断功能结构域，导致酶的抑制 活性，和c）区分潜在和酶的活化形式。