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    Matrix metalloproteinase inhibitor peptides
    51.
    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
    54.
    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。

    Real-time delivery of medical test data to portable communications devices
    58.
    发明授权
    Real-time delivery of medical test data to portable communications devices 有权

    公开(公告)号：US11074998B1

    公开(公告)日：2021-07-27

    申请号：US10130402

    申请日：2000-11-14

    申请人： Lance A. Liotta ,  Tyson Liotta

    发明人： Lance A. Liotta ,  Tyson Liotta

    IPC分类号： G16H20/10 ,  G16H40/67 ,  G16H40/20 ,  G16H10/40 ,  G16H50/30

    摘要： The present invention relates to a system and method for real-time delivery of medical tests and related data from laboratories (12) or similar sources (18) to portable communication devices such as mobile phones (14), text-enabled pagers (14) and web-enabled personal digital assistance (PDA's) (14) and other WAP devices (14). The subject system enables physicians to access test results remotely as soon as they become available. Also, the system allows the physician to develop an electronic prescription and submit the electronic prescription to a pharmacy using the portable communications device (14).

    Tissue Preservation and Fixation Method
    59.
    发明申请
    Tissue Preservation and Fixation Method 有权
    组织保存和固定方法

    公开(公告)号：US20130345075A1

    公开(公告)日：2013-12-26

    申请号：US13836995

    申请日：2013-03-15

    申请人： Virginia A. Espina ,  Lance A. Liotta ,  David Geho

    发明人： Virginia A. Espina ,  Lance A. Liotta ,  David Geho

    IPC分类号： G01N1/30

    CPC分类号： G01N1/30 ,  A01N1/00

    摘要： This invention relates, e.g., to a composition that, at room temperature, when contacted with a sample comprising phosphoproteins, can fix and stabilize cellular phosphoproteins, preserve cellular morphology, and allow the sample to be frozen to generate a cryostat frozen section suitable for molecular analysis. The composition comprises (1) a fixative that stabilizes the proteins in the sample and that has a sufficient water content for a stabilizer and/or a permeability enhancing agent to be soluble therein; (2) a stabilizer, comprising (a) a kinase inhibitor and (b) a phosphatase inhibitor and, optionally, (c) a protease (e.g., proteinase) inhibitor; (3) a permeability enhancing agent; and (4) lactic acid. Methods and kits are described for preserving phosphoproteins, using such a composition. Also described are endogenous surrogate markers for monitoring protein degradation, including the loss of posttranslational modifications (such as phosphorylation), e.g. following removal of a cell or tissue from a subject; and exogenous molecular sentinels (e.g. phosphoproteins attached to magnetic nanoparticles) that allow one to evaluate the processing history of a cellular or tissue population sample.

    摘要翻译： 本发明涉及例如在室温下与包含磷蛋白的样品接触时可以固定和稳定细胞磷酸蛋白的组合物，保留细胞形态，并允许样品冷冻以产生适于分子的低温恒温器冷冻切片 分析。 组合物包含（1）稳定样品中蛋白质并且具有足够的水含量的固定剂，用于稳定剂和/或渗透性增强剂可溶于其中; （2）稳定剂，其包含（a）激酶抑制剂和（b）磷酸酶抑制剂和任选的（c）蛋白酶（例如蛋白酶）抑制剂; （3）渗透增强剂; 和（4）乳酸。 描述了使用这种组合物来保存磷蛋白的方法和试剂盒。 还描述了用于监测蛋白质降解的内源替代标记，包括翻译后修饰（例如磷酸化）的丧失，例如， 从受试者中除去细胞或组织; 和外源性分子前哨蛋白（例如连接到磁性纳米颗粒的磷酸蛋白），其允许评价细胞或组织群体样品的加工历史。