公开(公告)号：WO1992008486A1

公开(公告)日：1992-05-29

申请号：PCT/US1991008376

申请日：1991-11-08

Applicant: WASHINGTON UNIVERSITY

Inventor： WASHINGTON UNIVERSITY ,  CURTISS, Roy, III ,  KELLY, Sandra, M.

IPC: A61K39/112

CPC classification number: C12R1/42 ,  A61K39/00 ,  A61K39/0275 ,  A61K2039/522 ,  C07K14/255 ,  C12N15/01 ,  Y02A50/407 ,  Y02A50/482 ,  Y02A50/484

Abstract: This invention provides immunogenic compositions for the immunization of a vertebrate or invertebrate comprising an avirulent derivative of S. typhi. The derivatives having a mutation of the cya and/or crp and/or cdt genes. The invention also provides immunogenic compositions for the immunization of a vertebrate and invertebrate comprising an avirulent derivative of the above type which is capable of expressing a recombinant gene derived from a pathogen of said vertebrate or invertebrate individual to produce an antigen capable of inducing an immune response against said pathogen. Other embodiments of the invention include methods of preparing immunogenic compositions from these strains, and strains useful in the preparation of the immunogenic compositions, as well as methods of stimulating the immune system to respond to an immunogenic antigen of S. typhi by administration of the immunogenic composition.

Abstract translation: 本发明提供了用于免疫含脊椎动物或无脊椎动物的免疫原性组合物，其包含伤寒沙利氏菌的无毒性衍生物。 具有cya和/或crp和/或cdt基因突变的衍生物。 本发明还提供用于免疫脊椎动物和无脊椎动物的免疫原性组合物，其包含上述类型的无毒力衍生物，其能够表达源自所述脊椎动物或无脊椎动物个体的病原体的重组基因以产生能够诱导免疫应答的抗原 针对所述病原体。 本发明的其它实施方案包括从这些菌株制备免疫原性组合物的方法，以及可用于制备免疫原性组合物的菌株，以及通过施用免疫原性刺激免疫系统对伤寒沙门氏菌的免疫原性抗原作出反应的方法 组成。

公开(公告)号：WO1991006317A1

公开(公告)日：1991-05-16

申请号：PCT/US1990006503

申请日：1990-11-02

Applicant: WASHINGTON UNIVERSITY

Inventor： WASHINGTON UNIVERSITY ,  CURTISS, Roy, III ,  MUNSON, MARYANN

IPC: A61K39/112

CPC classification number: A61K39/0275 ,  A61K2039/522 ,  Y02A50/482

Abstract: Vaccines are provided for treatment of individuals for infections by gram negative bacteria. The vaccines are comprised of live avirulent Salmonella which are able to induce immunity to homologous and to heterologous Salmonella serotypes, and to other gram-negative enteric bacteria. The Salmonella of which the vaccine is comprised possess at least one mutation in a gene which globally regulates other genes, and which also possess a mutation in at least one other of the following type: a mutation either in a gene encoding an enzyme in a lipopolysaccharide synthesis, which results in a reversibly rough phenotype; or in a gene which regulates the synthesis of iron-regulated OMPs, such that the mutation leads to constitutive expression of these proteins. Strains useful for the production of these vaccines are also provided.

Abstract translation: 提供疫苗用于治疗革兰氏阴性细菌感染的个体。 疫苗由无活力的沙门氏菌组成，能够诱导对同源和异源沙门氏菌血清型的免疫，以及其他革兰氏阴性肠细菌。 包含疫苗的沙门氏菌在全球调节其他基因的基因中具有至少一个突变，并且还具有至少另一种以下类型的突变：编码脂多糖中的酶的基因中的突变 合成，导致可逆的粗糙表型; 或在调节铁调节的OMP的合成的基因中，使得突变导致这些蛋白质的组成型表达。 还提供了可用于生产这些疫苗的菌株。

公开(公告)号：WO1991002262A1

公开(公告)日：1991-02-21

申请号：PCT/US1990004324

申请日：1990-08-07

Applicant: WASHINGTON UNIVERSITY

Inventor： WASHINGTON UNIVERSITY ,  ACKERMAN, Joseph, J., H. ,  CHEN, Wei

IPC: G01R33/34

CPC classification number: G01R33/3657 ,  G01R33/341 ,  G01R33/3621

Abstract: An RF probe (20) for use in magnetic resonance applications includes a transmitter coil (24) for transmitting RF energy to excite a specimen (34) and a receiver coil (28) for sensing the RF energy absorbed or emitted by the specimen (34) wherein the receiver coil (28) is electrically decoupled from the transmitter coil (24) through the geometrical shape and positioning of the receiver coil (28) with respect to the transmitter coil (24). The technique includes the concept of physically locating multiple elements of either a transmitter or receiver coil in a non-orthogonal manner such that the net current induced in the receiver coil (28) is equal to zero. In another embodiment, the receiver coil (28) has a primary coil loop (32) for placement immediately adjacent a specimen (34) and a secondary coil loop (30), said receiver coil loops (30, 32) being anti-phase and connected in series and wherein the secondary receiver coil loop (30) may be angularly rotated with respect to the transmit coil (24) in order to achieve a zero net induced current. In still another embodiment, the receiver coil (28) element has a pair of parallel connected anti-phase coil elements (30, 32) and the primary coil element (32) for placement immediately adjacent the specimen (34) has a reduced inductance.

公开(公告)号：WO1989003427A1

公开(公告)日：1989-04-20

申请号：PCT/US1988003496

申请日：1988-10-06

Applicant: WASHINGTON UNIVERSITY

Inventor： WASHINGTON UNIVERSITY ,  CURTISS Ray, III

IPC: C12N15/00

CPC classification number: C12N9/0008 ,  A61K39/04 ,  A61K2039/523 ,  C07K14/315 ,  C07K14/35 ,  C12N15/00 ,  C12N15/68 ,  C12R1/42 ,  C12Y102/01011 ,  Y02A50/484

Abstract: The invention encompasses methods of maintaining desired recombinant genes in a genetic population of cells expressing the recombinant gene. The methods utilize mutant cells which are characterized by a lack of a functioning native gene encoding an enzyme which is essential for cell survival, wherein this enzyme catalyses a step in the biosynthesis of an essential cell wall structural component and the presence of a first recombinant gene encoding an enzyme which is a functional replacement for the native enzyme, wherein the first recombinant gene cannot replace the defective chromosomal gene. The first recombinant gene is structurally linked to a second recombinant gene encoding a desired product. Loss of the first recombinant gene causes the cells to lyse when the cells are in an environment where a product due to the expression of the first recombinant gene is absent. The invention also encompasses methods of creating and isolating mutant cells with the above characteristics. The cells of the invention are useful for commercial production of desired products, for components of vaccines for immunizing individuals, and for release into the environment.

Abstract translation: 本发明包括在表达重组基因的细胞的遗传群体中维持所需重组基因的方法。 该方法利用突变细胞，其特征在于缺乏编码细胞存活所必需的酶的功能性天然基因，其中该酶催化必需细胞壁结构组分的生物合成和第一重组基因的存在 编码作为天然酶的功能性替代物的酶，其中第一重组基因不能代替有缺陷的染色体基因。 第一重组基因在结构上与编码所需产物的第二重组基因连接。 当细胞处于不存在第一重组基因表达的产物的环境中时，第一重组基因的损失导致细胞裂解。 本发明还包括产生和分离具有上述特征的突变细胞的方法。 本发明的细胞可用于商业生产所需产品，用于免疫个体的疫苗的组分和用于释放到环境中。

公开(公告)号：WO1988009667A1

公开(公告)日：1988-12-15

申请号：PCT/US1988001933

申请日：1988-06-08

Applicant: WASHINGTON UNIVERSITY

Inventor： WASHINGTON UNIVERSITY ,  LACY, Paul, E. ,  SCHARP, David, W. ,  RICORDI, Camillo

IPC: A61K37/00

CPC classification number: C12M45/09

Abstract: A method to obtain purified, well defined cell populations from intact organs by digestion of the distended organ with suitable proteolytic enzymes in the main lower chamber (101) of the isolator and harvest of cell subpopulation by screening the effluent from treatment of the organ with physiologically compatible medium by a filtration screen (104) permitting the passage of desired cells into the conical upper chamber (105) converging to an outlet port (106), but preventing the passage of larger particles. In this manner, the physical/mechanical disruption of the cell population is unnecessary because of recircularization of the media by input ports (103) which is aided by agitation enhancers (102). The cells are eased out of their structural matrix and harvested directly. Application of this method to the preparation of purified islets of Langerhans from intact pancreas is described.

公开(公告)号：WO1998012309A2

公开(公告)日：1998-03-26

申请号：PCT/US1997016216

申请日：1997-09-15

Applicant: WASHINGTON UNIVERSITY ,  GOLDBERG, Gregory, I.

Inventor： WASHINGTON UNIVERSITY

IPC: C12N09/64

CPC classification number: C12N9/6491 ,  C12N9/6489

Abstract: Disclosed are methods of cell surface activation and inhibition that involve the interaction of an inhibitor of matrix metalloprotease known as TIMP-2, with the enzyme, gelatinase-A (GelA). Critical to the methods of the invention is the discovery of a unique TIMP-2 binding site on the surface of the C-terminal domain (GelA-CTD) of the enzyme, which has been determined to be Asp , but which can also include other residues in the Ge1A-CTD domain with which Asp forms a contiguous surface, namely Gly , Phe , and Tyr . Identification of this binding site provides a useful target for the screening of MMP inhibitors and for prognosis and treatment of diseases in which MMPs are implicated. Compounds which are candidate MMP inhibitors can be structured to competitively inhibit cell surface activation.

Abstract translation: 公开了涉及称为TIMP-2的基质金属蛋白酶抑制剂与酶，明胶酶-A（GelA）的相互作用的细胞表面活化和抑制的方法。 本发明方法的关键在于已经确定为Asp <656>的酶的C末端结构域（GelA-CTD）的表面上发现了独特的TIMP-2结合位点，但是可以 还包括其中Asp <656>形成邻接表面的Ge1A-CTD结构域中的其他残基，即Gly 651，Phe 650和Tyr 636。 该结合位点的鉴定提供了用于筛选MMP抑制剂以及预后和治疗涉及MMP的疾病的有用靶标。 作为候选MMP抑制剂的化合物可以结构化以竞争性地抑制细胞表面活化。

公开(公告)号：WO1998003650A1

公开(公告)日：1998-01-29

申请号：PCT/US1997012210

申请日：1997-07-24

Applicant: WASHINGTON UNIVERSITY

Inventor： WASHINGTON UNIVERSITY ,  MILBRANDT, Jeffrey ,  ARAKI, Toshiyuki

IPC: C12N15/12

CPC classification number: C07K14/705 ,  A61K38/00 ,  C07K16/28

Abstract: The present invention provides novel ninjurin proteins. In a preferred embodiment, the ninjurin proteins are from rats or humans. The ninjurin proteins are cellular adhesion molecules which are expressed in a variety of tissue types. Ninjurin is a membrane bound protein, as it contains two putative transmembrane domains, with the extracellular domain containing at least one binding domain.

Abstract translation: 本发明提供了新型的神经蛋白。 在一个优选实施方案中，所述新疆嘌呤蛋白来自大鼠或人。 ninjurin蛋白是以各种组织类型表达的细胞粘附分子。 Ninjurin是膜结合蛋白，因为它含有两个推定的跨膜结构域，细胞外结构域含有至少一个结合结构域。

公开(公告)号：WO1997035566A1

公开(公告)日：1997-10-02

申请号：PCT/US1997004866

申请日：1997-03-25

Applicant: WASHINGTON UNIVERSITY

Inventor： WASHINGTON UNIVERSITY ,  WILLIAMSON, Joseph, R. ,  CORBETT, John, A. ,  MCDANIEL, Michael, L. ,  TILTON, Ronald, G.

IPC: A61K31/155

CPC classification number: A61K31/155

Abstract: A method is disclosed for inhibiting nitric oxide formation in a warm blooded mammal afflicted with a pathophysiologic condition manifested by acute and chronic inflammation which comprises administering to said mammal an effective nitric oxide inhibitory amount of aminoguanidine.

Abstract translation: 公开了一种抑制由急性和慢性炎症表现的病理生理状况的温血动物中一氧化氮形成的方法，其包括对所述哺乳动物施用有效的一氧化氮抑制量的氨基胍。

公开(公告)号：WO1997032473A1

公开(公告)日：1997-09-12

申请号：PCT/US1997003349

申请日：1997-03-03

Applicant: WASHINGTON UNIVERSITY

Inventor： WASHINGTON UNIVERSITY ,  PIWNICA-WORMS, Helen

IPC: A01N01/02

CPC classification number: C12N9/1205

Abstract: The invention provides isolated, purified and structurally defined DNA encoding Myt1Hu, isolated and purified Myt1Hu protein, a method for making Myt1Hu protein by expressing the DNA encoding Myt1Hu and methods for measuring levels of Myt1Hu in RNA or of Myt1Hu protein in a cell sample. Measurements of Myt1Hu mRNA comprising normal and cancerous cells are useful for detecting disorders of cell proliferation.

Abstract translation: 本发明提供编码Myt1Hu的分离，纯化和结构定义的DNA，分离和纯化的Myt1Hu蛋白，通过表达编码Myt1Hu的DNA制备Myt1Hu蛋白的方法和测量细胞样品中RNA或Myt1Hu蛋白中Myt1Hu水平的方法。 包含正常和癌细胞的Myt1Hu mRNA的测量可用于检测细胞增殖的病症。

公开(公告)号：WO1997020065A1

公开(公告)日：1997-06-05

申请号：PCT/US1996017783

申请日：1996-11-19

Applicant: WASHINGTON UNIVERSITY ,  STANLEY, Samuel, L., Jr.

Inventor： WASHINGTON UNIVERSITY

IPC: C12Q01/18

CPC classification number: C12Q1/18 ,  C12Q1/32

Abstract: There is disclosed an assay method of screening and identification of anti-amebic drugs which utilizes the ability to inhibit anaerobic growth of a novel bacterial mutant that expresses the EhADH2 gene and which bypasses the conventional need for a parasitic culture. The novel mutant, designated E. coli/EhADH2, is cultured under anaerobic conditions, a predetermined or known quantity of the agent to be tested or target compound is combined with the cell culture, and the combination is then monitored to determine the inhibitory effect upon the anaerobic growth of the E. coli/EhADH2 cell mutant.

Abstract translation: 公开了一种利用能够抑制表达EhADH2基因的新型细菌突变体的厌氧生长并且绕过常规需要寄生培养的抗阿米巴药物的筛选和鉴定的测定方法。 将命名为大肠杆菌/ EhADH2的新型突变体在厌氧条件下培养，预定或已知量的待测试试剂或目标化合物与细胞培养物组合，然后监测该组合以确定对 大肠杆菌/ EhADH2细胞突变体的厌氧生长。