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1. 发明申请

WO1997010493A1 METHOD FOR MEASURING NITROSYL (FeII)-HEMOGLOBIN 审中-公开
标题翻译：用于测量硝基（FeII）-HEMOGLOBIN的方法
公开(公告)号：WO1997010493A1
公开(公告)日：1997-03-20
申请号：PCT/US1996014660
申请日：1996-09-13
申请人： DUKE UNIVERSITY MEDICAL CENTER , STAMLER, Jonathan, S.
发明人： DUKE UNIVERSITY MEDICAL CENTER
IPC分类号： G01N21/63
CPC分类号： A61K31/04 , A61K31/00 , A61K31/095 , A61K31/195 , A61K47/6445 , A61K47/6901 , G01N21/631 , G01N21/76 , G01N33/721 , Y10T436/17 , Y10T436/170769 , Y10T436/176152 , Y10T436/177692 , Y10T436/178459 , Y10T436/179228 , Y10T436/25125
摘要： Nitrosyl (FeII)-hemoglobin can be detected in biological samples, using a method which involves injection of samples into a photolysis cell, prior to detection of chemiluminescence generated by the reaction between nitric oxide and ozone. This method is useful for monitoring the levels of nitric oxide bioactivity in both normal physiological states, and disease states, such as septic shock, atherosclerosis, thrombosis, hyperhomocysteinemia, pulmonary hypertension, malignancy, infections and central nervous system disorders.
摘要翻译：在检测由一氧化氮和臭氧之间的反应产生的化学发光之前，可以使用涉及将样品注入光解细胞的方法在生物样品中检测到亚硝酰基（FeII） - 血红蛋白。这种方法可用于监测正常生理状态和疾病状态（如败血性休克，动脉粥样硬化，血栓形成，高同型半胱氨酸血症，肺动脉高压，恶性肿瘤，感染和中枢神经系统疾病）中一氧化氮生物活性的水平。

2. 发明申请

WO1997009972A1 ERYTHROCYTES LOADED WITH S-NITROSOTHIOL AND USES THEREFOR 审中-公开
标题翻译：肾上腺素与S-硝基酪氨酸加载及其用途
公开(公告)号：WO1997009972A1
公开(公告)日：1997-03-20
申请号：PCT/US1996014664
申请日：1996-09-13
申请人： DUKE UNIVERSITY MEDICAL CENTER , STAMLER, Jonathan, S. , BONAVENTURA, Joseph
发明人： DUKE UNIVERSITY MEDICAL CENTER
IPC分类号： A61K31/00
CPC分类号： A61K33/00 , A61K31/00 , A61K31/04 , A61K31/095 , A61K31/195 , A61K35/18 , A61K47/54 , A61K47/6445 , A61K47/6901 , C07K14/00 , G01N21/631 , G01N21/76 , G01N33/721 , Y02A50/411 , Y02A50/423
摘要： Nitric oxide (NO) interacts with hemoglobin (Hb) at its metal centers, whereas S-nitrosothiols (RSNOs) can donate the NO group to beta 93 cysteine residues, thereby shielding the NO functionality from heme inactivation. S-nitrosylation of Hb is under the allosteric control of oxygen and the oxidation state of heme. NO group release from SNO-Hb is further facilitated by intracellular low molecular weight thiols, forming RSNOs which can be exported from the erythrocyte to regulate blood pressure. Red blood cells can be loaded with low molecular weight RSNOs to act as a delivery system for NO groups. Loaded red blood cells can be used in methods of therapy for conditions which are characterized by abnormal O2 metabolism of tissues, oxygen-related toxicity, abnormal vascular tone, abnormal red blood cell adhesion, or abnormal O2 delivery by red blood cells.
摘要翻译：一氧化氮（NO）在其金属中心与血红蛋白（Hb）相互作用，而S-亚硝基硫醇（RSNO）可以将NO基团提供给β93半胱氨酸残基，从而屏蔽NO功能不受血红素灭活。 Hb的S-亚硝基化在氧的变构控制下以及血红素的氧化态。通过细胞内低分子量硫醇进一步促进SNO-Hb的NO释放，形成可从红细胞输出以调节血压的RSNO。红细胞可以装载低分子量的RSNO作为NO +组的递送系统。加载的红细胞可用于以组织异常氧代谢，氧相关毒性，异常血管紧张，红细胞异常粘附或红细胞异常氧传递为特征的病症的治疗方法。

3. 发明申请

WO1997010265A1 NITROSATED HEMOGLOBINS AND THERAPEUTIC USES THEREFOR 审中-公开
标题翻译：硝酸羟胺和其治疗用途
公开(公告)号：WO1997010265A1
公开(公告)日：1997-03-20
申请号：PCT/US1996014659
申请日：1996-09-13
申请人： DUKE UNIVERSITY MEDICAL CENTER , STAMLER, Jonathan, S.
发明人： DUKE UNIVERSITY MEDICAL CENTER
IPC分类号： C07K14/00
CPC分类号： C07K14/00 , A61K31/00 , A61K31/04 , A61K31/095 , A61K31/195 , A61K35/18 , A61K38/42 , A61K47/6445 , A61K47/6901 , G01N21/631 , G01N21/76 , G01N33/721 , Y02A50/411 , Y10S514/832 , Y10S530/829 , A61K2300/00
摘要： S-nitrosothiols (RSNOs) can donate the NO group to the beta 93 cysteine residues of hemoglobin (Hb) without inactivating the heme. S-nitrosylation of Hb is under the allosteric control of oxygen and the oxidation state of heme. NO group release from S-nitrosohemoglobin (SNO-Hb) is further facilitated by intracellular low molecular weight thiols, forming RSNOs which can be exported from the erythrocyte to regulate blood pressure and platelet activation. SNO-Hb can be formed by reaction of Hb with S-nitrosothiol. This procedure avoids oxidation of the heme. Other methods can be used which are not specific only for thiol groups, but which nitrosate Hb more extensively, and may produce polynitrosated metHb as a product or intermediate product of the method. SNO-Hb in its various forms and combinations thereof (oxy, deoxy, met; specifically S-nitrosylated, or nitrosated or nitrated to various extents) can be administered to an animal or human where it is desired to oxygenate, to scavenge free radicals, or to release NO groups to tissues. Thiols and/or NO donating agents can also be administered to enhance the transfer of NO groups. Examples of conditions to be treated by SNO-Hbs or other nitrosated or nitrated forms of Hb include ischemic injury, hypertension, angina, reperfusion injury and inflammation, and disorders characterized by thrombosis.
摘要翻译： S-亚硝基硫醇（RSNO）可以将NO组提供给血红蛋白（Hb）的β93半胱氨酸残基而不使血红素失活。 Hb的S-亚硝基化在氧的变构控制下以及血红素的氧化态。通过细胞内低分子量硫醇进一步促进了S-亚硝基血红蛋白（SNO-Hb）的NO组释放，形成可以从红细胞输出以调节血压和血小板活化的RSNO。可以通过Hb与S-亚硝基硫醇的反应形成SNO-Hb。该方法避免血红素的氧化。可以使用其他方法，其不仅仅是硫醇基团特异性，而且更广泛地是亚硝酸盐Hb，并且可以产生作为该方法的产物或中间产物的多硝基化metHb。 SNO-Hb以其各种形式及其组合（氧，脱氧，饱和，特异地S-亚硝基化，或亚硝化或硝化至各种程度）可以施用于需要含氧化的动物或人，以清除自由基，或将NO +释放到组织中。也可以施用硫醇和/或NO给药剂以增强NO +转移。由SNO-Hbs或其他亚硝化或硝化形式的Hb治疗的病症的实例包括缺血性损伤，高血压，心绞痛，再灌注损伤和炎症以及以血栓形成为特征的疾病。

4. 发明申请

WO1995013805A1 USE OF NITRIC OXIDE SYNTHASE INHIBITORS IN THE TREATMENT OF AUTOIMMUNE DISEASES 审中-公开
标题翻译：氧化氮合酶抑制剂在治疗自身免疫性疾病中的应用
公开(公告)号：WO1995013805A1
公开(公告)日：1995-05-26
申请号：PCT/US1994013239
申请日：1994-11-17
申请人： DUKE UNIVERSITY MEDICAL CENTER , WEINBERG, J., Brice
发明人： DUKE UNIVERSITY MEDICAL CENTER
IPC分类号： A61K31/22
CPC分类号： A61K31/155 , A61K31/195 , A61K31/22
摘要： The invention relates to a method of treating or preventing autoimmune diseases, such as rheumatoid arthritis, insulin dependent diabetes mellitus, systemic lupus erythematosus and glomerulonephritis, comprising administering to a patient in need thereof an effective amount of a nitric oxide synthase inhibitor or a nitric oxide scavenger.
摘要翻译：本发明涉及治疗或预防自身免疫性疾病如类风湿性关节炎，胰岛素依赖性糖尿病，系统性红斑狼疮和肾小球性肾炎的方法，包括向有需要的患者施用有效量的一氧化氮合酶抑制剂或一氧化氮清道夫。

5. 发明申请

WO1998005689A1 POLYMERS FOR DELIVERING NITRIC OXIDE IN VIVO 审中-公开
标题翻译：聚合物在血液中输送氮氧化物
公开(公告)号：WO1998005689A1
公开(公告)日：1998-02-12
申请号：PCT/US1997013475
申请日：1997-07-28
申请人： DUKE UNIVERSITY MEDICAL CENTER
发明人： DUKE UNIVERSITY MEDICAL CENTER , STAMLER, Jonathan, S. , TOONE, Eric, J. , STACK, Richard, S.
IPC分类号： C08B37/00
CPC分类号： B82Y5/00 , A61K47/6951 , A61L31/10 , A61L31/16 , A61L2300/114 , A61L2300/416 , A61L2300/42 , C08B37/0012 , C08L5/16
摘要： Disclosed are novel polymers derivatized with at least one -NOX group per 1200 atomic mass unit of the polymer. X is one or two. In one embodiment, the polymer is an S-nitrosylated polymer and is prepared by reacting a polythiolated polymer with a nitrosylating agent under conditions suitable for nitrosylating free thiol groups. The polymers of the present invention can be used to coat medical devices to deliver nitric oxide in vivo to treatment sites.
摘要翻译：公开了以聚合物的每1200原子质量单位至少一个-NOX基团衍生的新型聚合物。 X是一两个。在一个实施方案中，聚合物是S-亚硝基化聚合物，并且通过使多硫醇化聚合物与亚硝酰化剂在适于亚硝酰化游离巯基的条件下反应来制备。本发明的聚合物可用于涂覆医疗装置以将体内的一氧化氮输送到治疗部位。

6. 发明申请

WO1986006843A1 DETERMINATION OF T1 RELAXATION TIMES USED IN AUTOMATED NUCLEAR MAGNETIC RESONANCE IMAGE SYNTHESIS 审中-公开
标题翻译：自动核磁共振图像合成中T1弛豫时间的确定
公开(公告)号：WO1986006843A1
公开(公告)日：1986-11-20
申请号：PCT/US1986001026
申请日：1986-05-15
申请人： DUKE UNIVERSITY MEDICAL CENTER
发明人： DUKE UNIVERSITY MEDICAL CENTER , RIEDERER, Stephen, J.
IPC分类号： G01R33/20
CPC分类号： G01N24/08 , G01R33/50
摘要： A method for providing improved estimates of the spin-lattice relaxation time (T1) of an image in a Nuclear Magnetic Resonance (NMR) technique on a human body which utilizes the application of a multiple spin-echo pulse sequence technique at two different pulse repetition times (TR1 and TR2). The signals for each of the different repetition times are measured by first setting the longitudinal magnetization (T1) to an initial value and then waiting the appropriate repetition time in order to provide the measured signal. The magnetization is "flipped" into the x-y plane and the relationship between the measured values for each of the repetition times is utilized to form an algorithm whereby the calculated ratio of the measured signals allows for an initial estimate of T1. The process also utilizes the plurality of spin-echos in the multiple spin-echo pulse sequence to appropriately measure, at each of the echo times TE(i), the decaying value of the measured first and second magnetization signals, which, in turn, provides further estimates of T1 which are then weight averaged.

7. 发明申请

WO1996039172A1 SUPPRESSOR OF HIV REPLICATION AND TRANSCRIPTION 审中-公开
标题翻译：艾滋病毒复制和转录的抑制剂
公开(公告)号：WO1996039172A1
公开(公告)日：1996-12-12
申请号：PCT/US1996008755
申请日：1996-06-05
申请人： DUKE UNIVERSITY MEDICAL CENTER
发明人： DUKE UNIVERSITY MEDICAL CENTER , BOLOGNESI, Dani, P. , CHEN, Chin-Ho , GREENBURG, Michael , WEINHOLD, Kent , LACEY, Simon, F.
IPC分类号： A61K38/19
CPC分类号： C12Q1/703 , A61K38/00 , C07K14/4703 , C12Q1/6897
摘要： The present invention relates to a bioactive molecule, herein referred to as the CD8 suppressor molecule, that is produced by the CD8 subset of human T-lymphocytes and suppresses type-1 human immunodeficiency virus (HIV-1) replication through inhibition of viral transcription. The invention relates to isolation of clonal CD8 cells lines that produce the entiviral activity and the development of an assay system for detection of the antiviral activity. The clonal cell lines and the assay system, described herein, may be utilized to purify, characterize and clone the CD8 suppressor molecule. The CD8 suppressor molecule may have therapeutic applications for treatment of diseases associated with HIV-1 infection.
摘要翻译：本发明涉及由人T淋巴细胞的CD8 +亚型产生并抑制1型人类免疫缺陷病毒（HIV-1）复制的生物活性分子（本文中称为CD8 +抑制分子）通过抑制病毒转录。本发明涉及分离产生宿主病毒活性的克隆CD8 +细胞系，并开发用于检测抗病毒活性的测定系统。本文所述的克隆细胞系和测定系统可用于纯化，表征和克隆CD8 +抑制分子。 CD8 +抑制分子可能具有用于治疗与HIV-1感染相关的疾病的治疗应用。

8. 发明申请

WO1995009365A1 METHODS AND COMPOSITIONS FOR TREATMENT OF BCR-ABL ASSOCIATED LEUKEMIAS AND OTHER CELL PROLIFERATIVE DISORDERS 审中-公开
标题翻译：用于治疗BCR-ABL相关性白血病和其他细胞增殖性疾病的方法和组合物
公开(公告)号：WO1995009365A1
公开(公告)日：1995-04-06
申请号：PCT/US1994011067
申请日：1994-09-28
申请人： NEW YORK UNIVERSITY MEDICAL CENTER , SUGEN, INC. , DUKE UNIVERSITY MEDICAL CENTER , SCHLESSINGER, Joseph , GISHIZKY, Mikhail, L. , PENDERGAST, Ann, M. , APP, Harald
发明人： NEW YORK UNIVERSITY MEDICAL CENTER , SUGEN, INC. , DUKE UNIVERSITY MEDICAL CENTER
IPC分类号： G01N33/574
CPC分类号： G01N33/5005 , A61K38/00 , C07K14/4705 , C07K14/82 , G01N33/5008 , G01N33/5011 , G01N33/5041 , G01N33/573 , G01N33/68
摘要： The present invention relates to compositions and methods for the prevention and treatment of cell proliferative disorders wherein a protein tyrosine kinase or protein tyrosine phosphatase capable of complexing with a member of the SH2- and/or SH3 domain-containing family of adaptor proteins is involved. This invention is based, in part, on the surprising discovery that the adaptor protein, GRB-2, binds the intracellular BCR-ABL tyrosine kinase product in vivo and is necessary for the activation of the oncogenic potential of the BCR/ABL product. The present invention further relates to protein tyrosine kinase/adaptor protein complexes and the uses of these complexes for the identification of agents capable of decreasing or inhibiting the interaction between the members of such complexes.
摘要翻译：本发明涉及用于预防和治疗细胞增殖性疾病的组合物和方法，其中涉及能够与适配蛋白的SH2-和/或SH3结构域的家族成员络合的蛋白质酪氨酸激酶或蛋白质酪氨酸磷酸酶。本发明部分基于令人惊奇的发现，即接头蛋白GRB-2在体内结合细胞内BCR-ABL酪氨酸激酶产物，并且是激活BCR / ABL产物的致癌潜力所必需的。本发明还涉及蛋白质酪氨酸激酶/衔接蛋白复合物以及这些复合物用于鉴定能够降低或抑制这些复合物成员之间相互作用的试剂的用途。

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