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71.
目的:为了探讨不同化疗药物作用于白血病细胞的特点,为临床化疗提供理论依据。方法:采用溴化四氮唑兰法(MTT法)研究了19例初治急性髓系白血病患有髓原代白血病细胞和K562细胞系体外对7种化疗药物及两药联合物敏感性。结果:柔红霉素(DNR)、威猛(VM26),三尖杉酯碱(H)和米托恩醒(MTT)体外杀伤白血病细胞作用较强,其中VM26、H的作用曲线比较独特。两种药物联合使用效果多数按近或好于单用效果 相似文献
72.
Protein S-thiolation is a process in which under oxidative stress, vulnerable sulfhydryl groups of proteins are conjugated to non-protein thiols such as glutathione (GSH) or cysteine resulting in the formation of protein-thiol mixed disulfides, protein-S-S-glutathione (PSSG) and protein-S-S-cysteine (PSSC). This process spontaneously disrupts the redox homeostasis of the cells, which in turn leads to functional disturbances in the respective tissue. In the ocular lens, such modification of proteins may trigger a cascade of events starting with the alteration of protein conformation, protein/enzyme deactivation, protein-S-S-protein aggregation and eventually lens opacification or cataract. Generally, the first line of defense system in the cells protects the lens proteins against such damage. Recent studies in our laboratory have shown that in addition to this defense system, lens cells also possess a well developed system to repair the oxidative damage to the lens proteins. We have identified this repair system as thioltransferase (TTase) and have proved that TTase by its dethiolase activity reverses the protein S-thiolation process which returns the oxidatively damaged lens proteins/enzymes to their original reduced state and restores their physiological functions. We investigated if this repair mechanism was mediated by enzymes other than TTase. We studied glutathione S-transferase (GST) and report here for the first time the cloning, high level expression, and purification of human lens mu and pi isoforms of GST. A comparative study of recombinant human lens TTase and GST (mu and pi) on their dethiolating abilities using lens crystallin-thiol mixed disulfides showed that the lens TTase is 60-70% more efficient in the dethiolation/repair process than GST. When TTase and GST were tested in conjunction for the dethiolation of thiol mixed disulfides, there was no significant enhancement of dethiolase activity. These findings suggest that TTase by itself is an efficient enzyme in the dethiolation/repair process and hence can be considered a crucial system to counteract oxidative stress in the lens. 相似文献
73.
S Wang M Liu N E Lewin P S Lorenzo D Bhattacharrya L Qiao A P Kozikowski P M Blumberg 《Journal of medicinal chemistry》1999,42(18):3436-3446
Protein kinase C (PKC) comprises a family of ubiquitous enzymes transducing signals by the lipophilic second messenger sn-1, 2-diacylglycerol (DAG). Teleocidin and its structurally simpler congener indolactam-V (ILV) bind to PKC with high affinity. In this paper, we report our computational docking studies on ILV binding to PKC using an automatic docking computer program, MCDOCK. In addition, we used site-directed mutagenesis to assess the quantitative contribution of crucial residues around the binding site of PKC to the binding affinity of ILV to PKC. On the basis of the docking studies, ILV binds to PKC in its cis-twist conformation and forms a number of optimal hydrogen bond interactions. In addition, the hydrophobic groups in ILV form "specific" hydrophobic interactions with side chains of a number of conserved hydrophobic residues in PKC. The predicted binding mode for ILV is entirely consistent with known structure-activity relationships and with our mutational analysis. Our mutational analysis establishes the quantitative contributions of a number of conserved residues to the binding of PKC to ILV. Taken together, our computational docking simulations and analysis by site-directed mutagenesis provide a clear understanding of the interaction between ILV and PKC and the structural basis for design of novel, high-affinity, and isozyme-selective PKC ligands. 相似文献
74.
75.
高效液相色谱法测定美洛昔康胶囊的含量 总被引:1,自引:0,他引:1
目的 :建立反相高效液相色谱法测定美洛昔康胶囊中美洛昔康的含量。方法 :采用LichrosorbC18色谱柱 (5 μm,4 .6mm× 2 0 0mm) ,以吡罗昔康为内标 ,甲醇 乙腈 0 .0 9mol·L-1庚烷磺酸钠溶液 冰醋酸 (5 4∶8∶37∶1)为流动相 ,流速为0 .9mL·min-1,检测波长为 35 2nm ,柱温为室温。结果 :美洛昔康在 8~ 4 8mg·L-1范围内呈良好的线性关系 ,r =0 .9999,平均回收率为 99.78% ,RSD为 0 .96 %。结论 :该法简便 ,快速 ,专属性好 ,结果准确 ,可靠。 相似文献
76.
77.
实体语法系统与中医药理论现代化 总被引:1,自引:0,他引:1
实体语法系统是一种形式化语法系统,可用于形式化地描述复杂系统的组成单位、组织方式、变化规律。本文尝试将实体语法系统引入中医药理论研究,为实现中医药理论的形式化提供一种新的思路,并在此基础上探讨实现中医药理论与微观领域知识的衔接和用中医药理论解释人体复杂系统的可能性。实体语法系统为中医药理论形式化和中医药理论现代化提供了较具体的研究工具,为中医药理论现代化提出了探索性的思路。 相似文献
78.
Polymorphisms in interleukin -2, -6, and -10 are not associated with gastric cardia or esophageal cancer in a high-risk chinese population. 总被引:7,自引:0,他引:7
79.
Wen Qing Yang Xueqing Lun Cheryl Ann Palmer M Elizabeth Wilcox Huong Muzik Zhong Qiao Shi Richard Dyck Matt Coffey Brad Thompson Mark Hamilton Sandra G Nishikawa Penny M A Brasher Kevin Fonseca David George N Berry Rewcastle Randal N Johnston Doug Stewart Patrick W K Lee Donna L Senger Peter A Forsyth 《Clinical cancer research》2004,10(24):8561-8576
PURPOSE: Human reovirus type 3 has been proposed to kill cancer cells with an activated Ras signaling pathway. The purpose of this study was to investigate the efficacy of reovirus in immunocompetent glioma animal models and safety/toxicity in immunocompetent animals, including nonhuman primates. EXPERIMENTAL DESIGN: Racine glioma cells 9L and RG2 were implanted s.c. or intracranially in Fisher 344 rats with or without reovirus antibodies, followed by treatment of reovirus. To study whether reovirus kills contralateral tumors in the brain and to determine viral distribution, we established an in situ dual tumor model followed by reovirus intratumoral inoculation only into the ipsilateral tumor. To evaluate neurotoxicity/safety of reovirus, Cynomolgus monkeys and immunocompetent rats were given intracranially with reovirus, and pathological examination and/or behavioral studies were done. Viral shedding and clinical biochemistry were systematically studied in monkeys. RESULTS: Intratumorally given reovirus significantly suppressed the growth of both s.c. and intracranially tumors and significantly prolonged survival. The presence of reovirus-neutralizing antibodies did not abort the reovirus' antitumor effect. Reovirus inhibited glioma growth intracranially in the ipsilateral but not the contralateral tumors; viral load in ipsilateral tumors was 15 to 330-fold higher than the contralateral tumors. No encephalitis or behavioral abnormalities were found in monkeys and rats given reovirus intracranially. No treatment-related clinical biochemistry changes or diffuse histopathological abnormality were found in monkeys inoculated intracranially with Good Manufacturing Practice prepared reovirus. Microscopic changes were confined to the region of viral inoculation and were dose related, suggesting reovirus intracranially was well tolerated in nonhuman primates. CONCLUSIONS: These data show the efficacy and safety of reovirus when it is used in the treatment of gliomas in immunocompetent hosts. Inoculation of reovirus into the brain of nonhuman primates did not produce significant toxicities. 相似文献
80.
6名健康妇女分别于上臂、臀部和腹部三部位经皮给予合LNG的透皮控释传递系统(TCDS)后,用放射免疫法测定LNG血清浓度,计算其主要药物动力学参数。结果表明:在TCDS用药期间,三部位的C(max)、T(max)及AUC(0~168h)基本接近,部位间无显著性差异(P>0.05);TCDS揭除后,AUC(168~204h)及消除相半衰期T(1/2)(Ke)均以腹部最大,臀部次之,上臂最小,在腹部与上臂间有显著性差异(P<0.05)。上述结果可归因于TCDS对LNG的控释和人体皮下脂肪的“贮库效应”。 相似文献