公开(公告)号：WO1993016723A1

公开(公告)日：1993-09-02

申请号：PCT/US1993001558

申请日：1993-02-24

Applicant: VANDERBILT UNIVERSITY ,  COVER, Timothy, L. ,  BLASER, Martin, J.

Inventor： VANDERBILT UNIVERSITY

IPC: A61K39/00

CPC classification number: G01N33/56911 ,  A61K31/365 ,  A61K38/00 ,  A61K39/00 ,  C07K14/205 ,  C07K16/121 ,  G01N2333/205

Abstract: This invention relates to a purified Helicobacter pylori vacuolating toxin and methods to use this toxin to produce protective antibodies against H. pylori infection. Antiserum to this antigen can be used to detect the toxin. Methods to detect anti-toxin antibodies determine the susceptibility of a patient to develop peptic ulcer disease, gastric carcinoma, or other clinical consequences of H. pylori infection.

Abstract translation: 本发明涉及纯化的幽门螺杆菌空泡毒素和使用该毒素产生针对幽门螺杆菌感染的保护性抗体的方法。 该抗原的抗血清可用于检测毒素。 检测抗毒素抗体的方法决定了患者发生消化性溃疡病，胃癌或幽门螺杆菌感染的其他临床后果的易感性。

公开(公告)号：WO1998012312A1

公开(公告)日：1998-03-26

申请号：PCT/US1997016628

申请日：1997-09-18

Applicant: VANDERBILT UNIVERSITY ,  WRIGHT STATE UNIVERSITY ,  STECENKO, Arlene ,  BERNSTEIN, Jack, M.

Inventor： VANDERBILT UNIVERSITY ,  WRIGHT STATE UNIVERSITY

IPC: C12N15/00

CPC classification number: C12N15/1131 ,  A61K38/00 ,  C12N2310/111 ,  Y02A50/463

Abstract: A vector and methods of inhibiting replication of an RNA virus which replicates in the cytoplasm of a cell in a subject, comprising administering to the cell of the subject a composition comprising a vector comprising a promoter functionally linked to a nucleic acid comprising a viral gene, wherein the nucleic acid is in antisense orientation relative to the promoter and wherein the cell is capable of promoting expression from the promoter, thereby transcribing the nucleic acid and inhibiting replication of the RNA virus in the subject. In particular, provided are vectors and methods for treating a respiratory syncytial virus infection.

Abstract translation: 一种载体和抑制在受试者的细胞的细胞质中复制的RNA病毒的复制的方法，包括向受试者的细胞施用包含与包含病毒基因的核酸功能性连接的启动子的载体的组合物， 其中所述核酸相对于启动子处于反义方向，并且其中所述细胞能够促进来自所述启动子的表达，从而转录所述核酸并抑制所述受试者中RNA病毒的复制。 特别地，提供了用于治疗呼吸道合胞病毒感染的载体和方法。

公开(公告)号：WO1997030108A1

公开(公告)日：1997-08-21

申请号：PCT/US1997003340

申请日：1997-02-19

Applicant: VANDERBILT UNIVERSITY ,  UNIVERSITY OF WASHINGTON

Inventor： VANDERBILT UNIVERSITY ,  UNIVERSITY OF WASHINGTON ,  HOLT, Jeffrey, T. ,  JENSEN, Roy, A. ,  CLAIRE-KING, Marie ,  PAGE, David, L. ,  SZABO, Csilla, I. ,  JETTON, Thomas, L. ,  ROBINSON-BENION, Cheryl, L. ,  THOMPSON, Marilyn, E.

IPC: C08H01/00

CPC classification number: A61K49/0004 ,  A61K38/00 ,  A61K48/00 ,  C07K14/4703 ,  C07K2319/00

Abstract: Genetic analysis of familial breast and ovarian cancer indicates that BRCA1 is a tumor suppressor gene. The BRCA1 gene encodes a 190 kDa protein with sequence homology and biochemical analogy to the granin family of proteins. Granins are secreted from endocrine cells via the regulated secretory pathway and are proteolytically cleaved to yield biologically active peptides. BRCA1 protein localises to secretory vesicles, and was demonstrated to be secreted. Gene transfer of BRCA1 inhibits growth and tumorigenesis of breast and ovarian cancer cells, but not colon or lung cancer cells or fibroplasts, suggesting that BRCA1 encodes a tissue-specific growth inhibitor. Thus, BRCA1 is a secreted growth inhibitor and functions by a mechanism not previously described for tumor suppressor genes. The BRCA2 breast and ovarian cancer gene encodes a protein that also includes a granin region, indicating that the BRCA2 protein is also a secreted tumor suppressor. Therapeutic methods using the BRCA1 and BRCA proteins and genes are also described. A method of screening for the receptors of the BRCA1 protein and BRCA2 proteins is also described.

Abstract translation: 家族性乳腺癌和卵巢癌的遗传分析表明，BRCA1是肿瘤抑制基因。 BRCA1基因编码190 kDa的蛋白质，与蛋白质的大豆蛋白家族具有序列同源性和生物化学类比。 通过经调节的分泌途径从内分泌细胞分泌颗粒，并被蛋白水解切割以产生生物活性肽。 BRCA1蛋白定位于分泌囊泡，并被证明是分泌的。 BRCA1的基因转移抑制乳腺和卵巢癌细胞的生长和肿瘤发生，但不抑制结肠或肺癌细胞或纤维板，这表明BRCA1编码组织特异性生长抑制剂。 因此，BRCA1是分泌的生长抑制剂，并且通过以前未被描述用于肿瘤抑制基因的机制起作用。 BRCA2乳腺癌和卵巢癌基因编码的蛋白质也包括一个颗粒蛋白，表明BRCA2蛋白也是分泌的肿瘤抑制因子。 还描述了使用BRCA1和BRCA蛋白和基因的治疗方法。 还描述了筛选BRCA1蛋白和BRCA2蛋白的受体的方法。

公开(公告)号：WO1996038863A1

公开(公告)日：1996-12-05

申请号：PCT/US1996007917

申请日：1996-05-29

Applicant: VANDERBILT UNIVERSITY

Inventor： VANDERBILT UNIVERSITY ,  KANG, Weng, Poo ,  DAVIDSON, Jimmy, Lee ,  KERNS, David, V., Jr.

IPC: H01L31/0256

CPC classification number: G01N27/129 ,  H01L2924/0002 ,  H01L2924/00

Abstract: A solid state chemical sensing device (10) is described in which a chemically sensitive electrode (30), an intrinsic (undoped) diamond layer (25), and a doped diamond layer (20) are deposited on a conductive or insulating substrate (15). At least one of the chemically sensitive electrode (30) or doped diamond layer (20) must make ohmic contact to the intrinsic diamond layer (25). The device (10) forms a sensing structure in which conduction of current through the device (10) in the presence of a target chemical is dominated by space charged limited current, thereby providing enhanced sensitivity and selectivity.

Abstract translation: 描述了一种固态化学感测装置（10），其中化学敏感电极（30），本征（未掺杂）金刚石层（25）和掺杂金刚石层（20）沉积在导电或绝缘衬底（15）上 ）。 化学敏感电极（30）或掺杂金刚石层（20）中的至少一个必须与本征金刚石层（25）形成欧姆接触。 器件（10）形成感测结构，其中在存在目标化学物质的情况下通过器件（10）的电流传导由空间带电限制电流控制，从而提供增强的灵敏度和选择性。

公开(公告)号：WO1996011019A1

公开(公告)日：1996-04-18

申请号：PCT/US1995012656

申请日：1995-10-02

Applicant: VANDERBILT UNIVERSITY

Inventor： VANDERBILT UNIVERSITY ,  GRAHAM, Barney, S. ,  TANG, Yi-Wei

IPC: A61K39/155

CPC classification number: C07K16/1027 ,  A61K39/12 ,  A61K39/155 ,  A61K39/39 ,  A61K2039/5252 ,  A61K2039/55538 ,  A61K2039/57 ,  C07K2317/52 ,  C12N2760/18534

Abstract: A method is disclosed of reducing viral replication of a virus of the Paramyxoviridae family in a host, comprising administering to the host an antigen of the virus in combination whith an effective adjuvant amount of interleukin-12 (IL-12). Human viruses of the Paramyxoviridae family include paramyxoviruses (e.g., parainfluenza virus 1, parainfluenza virus 2, parainfluenza virus 3 and parainfluenza virus 4), morbilliviruses (e.g., measles virus) and pneumoviruses (e.g., respiratory syncytial virus); other non-human viruses of the Paramyxoviridae family include canine distemper virus, bovine respiratory syncytial virus, Newcastle disease virus and rhinderpest virus. A composition is also disclosed comprising a mixture of an antigen of a virus of the Paramyxoviridae family and an effective adjuvant amount of interleukin-12 (IL-12).

Abstract translation: 公开了减少宿主中副粘病毒科病毒的病毒复制的方法，包括以有效的佐剂量的白细胞介素-12（IL-12）组合给予宿主病毒抗原。 副粘病毒科的人类病毒包括副粘病毒（例如副流感病毒1，副流感病毒2，副流感病毒3和副流感病毒4），斑疹病毒（例如麻疹病毒）和肺炎链球菌（例如呼吸道合胞病毒）; 副粘病毒科其他非人类病毒包括犬瘟热病毒，牛呼吸道合胞病毒，新城疫病毒和牛瘟病毒。 还公开了一种组合物，其包含副粘病毒科的病毒抗原与有效佐剂量的白细胞介素-12（IL-12）的混合物。

公开(公告)号：WO1996010074A1

公开(公告)日：1996-04-04

申请号：PCT/US1995013051

申请日：1995-09-27

Applicant: VANDERBILT UNIVERSITY

Inventor： VANDERBILT UNIVERSITY ,  CAPDEVILLA, Jorge ,  MAKITA, Keiko ,  KARARA, Armando

IPC: C12N05/00

CPC classification number: C12N9/0077 ,  A61K49/0004

Abstract: The invention provides an isolated nucleic acid encoding the rat P450 2C11 arachidonic acid epoxygenase, or a human homologue thereof, having a mutation associated with salt induced hypertension. Also provided is an isolated cell line expressing the epoxygenase encoded by the emutated nucleic acid, and a non-human transgenic animal having a germ line insertion of the mutated nucleic acid. Also provided is a method of screening a compound for efficacy in treating salt induced hypertension comprising administering the compound to such a non-human transgenic animal, and detecting an improvement in the animal's hypertension. The invention also provides a method of screening a human subject for a genetic predisposition to salt induced hypertension comprising detecting a mutation in a human homologue of a rat P450 2C11 arachidonic acid epoxygenase gene which affects normal epoxygenase activity. Also provided is a method of treating salt induced hypertension in a human subject associated with a genetic mutation in a human homologue of the rat P450 2C11 arachidonic acid epoxygenase gene, comprising administering to the subject a functional metabolite, or analogue thereof, produced by the human homologue of the rat P450 2C11 arachidonic acid epoxygenase. Also provided is an isolated mutated rat P450 2C11 arachidonic acid epoxygenase, or a human homologue thereof, having a mutation associated with salt induced hypertension.

Abstract translation: 本发明提供编码具有与盐诱导的高血压相关的突变的大鼠P450 2C11花生四烯酸环氧化酶或其人类同源物的分离的核酸。 还提供了表达由引发的核酸编码的环氧化酶的分离的细胞系和具有突变核酸的种系插入的非人转基因动物。 还提供了筛选化合物以治疗盐诱导的高血压的功效的方法，包括给予这种非人转基因动物的化合物，并检测动物的高血压的改善。 本发明还提供了筛选人类受试者对盐诱导的高血压的遗传易感性的方法，包括检测影响正常环氧化酶活性的大鼠P450 2C11花生四烯酸环氧化酶基因的人类同源物中的突变。 还提供了一种治疗与大鼠P450 2C11花生四烯酸环氧化酶基因的人同源物中的遗传突变相关的人类受试者的盐诱导的高血压的方法，包括向受试者施用由人产生的功能性代谢物或其类似物 大鼠P450 2C11花生四烯酸环氧化酶的同系物。 还提供了具有与盐诱发的高血压相关的突变的分离的突变大鼠P450 2C11花生四烯酸环氧化酶或其人类同源物。

公开(公告)号：WO1995019369A1

公开(公告)日：1995-07-20

申请号：PCT/US1995000608

申请日：1995-01-17

Applicant: VANDERBILT UNIVERSITY

Inventor： VANDERBILT UNIVERSITY ,  HOLT, Jeffrey, T. ,  JENSEN, Roy, A. ,  PAGE, David, L. ,  OBERMILLER, Patrice, S. ,  ROBINSON-BENION, Cheryl, L. ,  THOMPSON, Marilyn, E.

IPC: C07H21/02

CPC classification number: G01N33/57415 ,  C07K14/82 ,  C12Q1/6886 ,  C12Q2600/112 ,  C12Q2600/136 ,  C12Q2600/158

Abstract: The present invention provides a method of detecting and diagnosing pre-invasive breast cancer by identifying differentially expressed genes in early, pre-invasive breast cancer tissue. Differentially expressed genes can be used as genetic markers to indicate the presence of pre-invasive cancerous tissues. Microscopically directed tissue sampling techniques combined with differential display or differential screening of cDNA libraries are used to determine differential expression of genes in the early stages of breast cancer. Differential expression of genes in pre-invasive breast cancer tissue is confirmed by RT-PCR, nuclease protection assays and in-situ hybridization of ductal carcinoma in situ tissue RNA and control tissue RNA. The present invention also provides a method of screening for compounds that induce expression of the BRCA1 gene, whose product negatively regulates cell growth in both normal and malignant mammary epithlial cells. The present invention also relates to gene therapy method using this gene.

Abstract translation: 本发明提供了一种通过在早期浸润性乳腺癌组织中识别差异表达的基因来检测和诊断浸润性乳腺癌的方法。 差异表达的基因可用作遗传标记，以指示侵入性癌组织的存在。 使用显微指导的组织采样技术与差异显示或差异筛选cDNA文库来确定乳腺癌早期基因的差异表达。 通过RT-PCR，核酸酶保护测定和导管癌原位组织RNA和对照组织RNA的原位杂交来证实前浸润性乳腺癌组织中基因的差异表达。 本发明还提供了筛选诱导BRCA1基因表达的化合物的方法，所述BRCA1基因的产物负调节正常和恶性乳腺上皮细胞中的细胞生长。 本发明还涉及使用该基因的基因治疗方法。

公开(公告)号：WO1994028125A2

公开(公告)日：1994-12-08

申请号：PCT/CA1994000296

申请日：1994-05-25

Applicant: MERCK FROSST CANADA INC. ,  VANDERBILT UNIVERSITY ,  FORD-HUTCHINSON, Anthony ,  FUNK, Colin ,  GRYGORCZYK, Richard ,  METTERS, Kathleen

Inventor： MERCK FROSST CANADA INC. ,  VANDERBILT UNIVERSITY

IPC: C12N15/12

CPC classification number: C07K14/72

Abstract: A novel prostaglandin receptor has been identified and DNA encoding the receptor has been isolated, purified, sequenced and expressed in host cells. This DNA encoding the novel prostaglandin receptor and host cells expressing the receptor are used to identify modulators of the prostaglandin receptor.

Abstract translation: 已经鉴定了一种新的前列腺素受体，并且已经分离，纯化，测序并在宿主细胞中表达编码受体的DNA。 编码新型前列腺素受体的DNA和表达受体的宿主细胞用于鉴定前列腺素受体的调节剂。

公开(公告)号：WO1993021949A1

公开(公告)日：1993-11-11

申请号：PCT/US1993003784

申请日：1993-04-22

Applicant: VANDERBILT UNIVERSITY

Inventor： VANDERBILT UNIVERSITY ,  WELLS, Jack, N. ,  PONG, Amy, Sue

IPC: A61K39/00

CPC classification number: C07K16/44

Abstract: The invention provides purified antibodies specifically reactive with an 8-(cycloalkyl or aromatic) substituted-1,3-dipropylxanthine such as 1,3-dipropyl-8-cyclohexylxanthine and 1,3-dipropyl-8-cyclopentylxanthine. Also provided is a method of conjugating an immunogenic water soluble protein to an 8-(cycloalkyl or aromatic) substituted-1,3-dipropylxanthine, comprising combining: (a) an aqueous solution comprising a conjugate-forming amount of an immunogenic water-soluble protein dissolved therein; and (b) an organic solution comprising a non-reactive, water-miscible organic solvent and a conjugate-forming amount of an 8-(cycloalkyl or aromatic) substituted-1,3-dipropylxanthine dissolved therein, wherein the ratio of the amount of aqueous solution to the amount of organic solution does not precipitate either the water soluble protein or the 8-(cycloalkyl or aromatic) substituted-1,3-dipropylxanthine, to form a protein 8-(cycloalkyl or aromatic) substituted-1,3-dipropylxanthine conjugate. In addition, the invention provides a method of detecting an 8-(cycloalkyl or aromatic) substituted-1,3-dipropylxanthine in a sample comprising contacting the antibodies of claim 1 with the 8-(cycloalkyl or aromatic) substituted-1,3-dipropylxanthine and detecting the presence of binding between the antibody and the 8-(cycloalkyl or aromatic) substituted-1,3-dipropylxanthine.

Abstract translation: 本发明提供了与8-（环烷基或芳族）取代的1,3-二丙基黄嘌呤如1,3-二丙基-8-环己基黄嘌呤和1,3-二丙基-8-环戊基黄嘌呤特异性反应的纯化抗体。 还提供了将免疫原性水溶性蛋白质与8-（环烷基或芳族）取代的1,3-二丙基黄嘌呤缀合的方法，其包括组合：（a）包含缀合物形成量的免疫原性水溶性 蛋白质溶解于其中; 和（b）包含非反应性，水混溶性有机溶剂和共轭形成量的溶解在其中的8-（环烷基或芳族）取代-1,3-二丙基黄嘌呤的有机溶液，其中， 水溶液与有机溶液的量不会沉淀水溶性蛋白质或8-（环烷基或芳族）取代的1,3-二丙基黄嘌呤，形成蛋白质8-（环烷基或芳族）取代的1,3-二丙基黄嘌呤， 二丙基黄嘌呤缀合物。 另外，本发明提供一种检测样品中8-（环烷基或芳族）取代-1,3-二丙基黄嘌呤的方法，包括使权利要求1的抗体与8-（环烷基或芳族）取代的1,3-二丙基黄嘌呤 检测抗体与8-（环烷基或芳族）取代-1,3-二丙基黄嘌呤之间的结合的存在。

公开(公告)号：WO1992021039A1

公开(公告)日：1992-11-26

申请号：PCT/US1992004027

申请日：1992-05-14

Applicant: VANDERBILT UNIVERSITY ,  E.I. DU PONT DE NEMOURS AND COMPANY

Inventor： VANDERBILT UNIVERSITY ,  E.I. DU PONT DE NEMOURS AND COMPANY ,  LAUDER, Alan ,  WIKSWO, John, P.

IPC: G01R33/10

CPC classification number: G01R33/10 ,  G01R33/16

Abstract: The surface of internal structure of diamagnetic and paramagnetic materials is imaged by measuring, preferably with a superconducting quantum interference device (SQUID) magnetometer (7), perturbations to an applied magnetic field resulting from variations in magnetic susceptibility at an array of locations across the object (3). The array of perturbation measurements is processed to generate a map of local susceptibilities. For implementation of susceptibility tomography, multiple arrays of perturbation signals for a plurality of relative orientations between the object, the field, and the measurement locations are processed to generate values for local susceptibility at selected sites within the object, such as along a selected sectional plane.

Abstract translation: 通过测量优选使用超导量子干涉装置（SQUID）磁强计（7）对所施加的磁场的扰动，通过测量穿过该物体的位置阵列处的磁化率的变化而对抗磁性和顺磁材料的内部结构的表面进行成像 （3）。 处理扰动测量数组以产生局部敏感度图。 为了实现敏感性层析成像，处理对象，场和测量位置之间的多个相对取向的多个扰动信号阵列，以在物体内的选定位置处产生用于局部敏感性的值，例如沿着选定的截面 。