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141.
目的
观察环氧化酶-2(cyclooxygenase-2,COX-2)选择性抑制剂塞来昔布对化学致癌剂7,12-二甲基苯蒽(7,12-dimethybenz[a]anthracene,DMBA)化学诱发的大鼠乳腺癌的抑制作用并探讨其机制.方法
将DMBA油剂灌胃复制大鼠乳腺癌模型,大鼠分为对照组(24只)和实验组(25只),观察塞来昔布对大鼠乳腺癌的抑制作用,并采用基因芯片技术了解治疗后2组肿瘤的基因表达谱差异.结果
实验组塞来昔布处理后乳腺肿瘤的数目、直径、体积分别为(2.56±1.26)个、(1.162±0.355)cm、(1.967±1.725)cm.;明显小于实验前的(3.40±1.22)个、(1.948±0.481)cm、(8.794±6.389)cm3;明显小于对照组(3.88±1.73)个、(2.231±0.736)cm、(10.268±5.447)cm3,差异有显著性意义(均P<0.01).对照组COX一2蛋白表达为62.5%(15/24),实验组COX-2蛋白表达为36.0%(9/25),差异有显著性意义(P<O.05).基因表达谱显示两组之间表达丰度差异2倍及以上的基因共有243条,其中表达上调2倍或以上的基因片段124条,表达下调2倍或以上的基因片段119条,发现功能不明的新基因6条,其中表达上调的4条.结论
塞来昔布能抑制DMBA诱发的大鼠乳腺癌进展,其机制和多种基因改变有关. 相似文献
142.
Youngnam Kang Takashi Okada Harunori Ohmori 《The European journal of neuroscience》1998,10(4):1363-1375
We report here on the ionic mechanisms underlying the depolarizing afterpotential (DAP) in neocortical pyramidal cells, with special interest in those underlying the burst afterdischarge. Injections of short depolarizing current pulses under whole-cell current clamp with a CsCl-based internal medium generated, in most pyramidal cells, a single action potential with a plateau phase (plateau-AP), followed by a slowly decaying DAP both in the absence and presence of TTX. Under voltage-clamp, the same cells displayed a slow tail current (tail-I) at the offset of depolarization. When intracellular free Ca2+ was chelated with 10 mm BAPTA or when extracellular Ca2+ was replaced with equimolar Ba2+, neither the slow DAP nor the slow tail-I was observed. Extracellular application of Co2+ or Cd2+ reduced Ca2+ currents and the slow tail-I. Cation substitution experiments revealed that the channel generating the slow tail-I was permeable to K+ and Cs+ more than to Na+ (PK≈PCs > PNa > PNMDG≈PTEA). The cationic slow tail-I was not reduced by applying antagonists of the metabotropic glutamate receptor (MCPG, 1 mm ) and the muscarinic receptor (atropine, 1–10 μm ). Thus, the slow DAP was produced by activation of the cationic channel whose gating is solely dependent on [Ca2+]i. An increase in [K+]o from 3 to 6 or 9 mm enhanced the slow DAP, and resulted in a generation of burst afterdischarges. An anticonvulsant, phenytoin (PT; 1–10 μm ) suppressed the slow DAP while enhancing the plateau-AP in the presence of TTX, most likely by blocking the cationic channel. 相似文献
143.
The binding of type I collagen to its receptor initiates platelet aggregation, but the relationship of the receptor to other signal transduction components is not yet established. Correlation of platelet aggregation and anti-type I collagen receptor antibody immunoprecipitation of type I collagen treated [32PO4]-labeled platelets showed that there are two phosphoproteins (Mr 53 kDa and 21 kDa) that coprecipitated with the 65 kDa platelet type I collagen receptor. In the present investigation, we have identified one of the phosphoproteins. A soluble component the 100,000×g supernatant fraction of 53 kDa protein is recognized by polyclonal anti-PP1 antibody. The activity of the precipitated phosphatase is inhibited by okadaic acid and inhibitor 1, suggesting that it is protein phosphatase 1 (PP 1). Phosphorylation decreases PP 1 activity as was found with [32PO4]-phosphorylase b as the substrate. The immunocoprecipitation of the type-1 collagen receptor and PP 1 inot the result of cross reactivity of the anti-type I collagen receptor antibody with the PP I protein. These results indicate that the platelet type I collagen receptor, PP 1, and unidentified 21 kDa protein are in close association with the platelet type I collagen receptor upon the binding of type I collagen by the receptor. Copyright © 1996 Elsevier Science Ltd 相似文献
144.
Summary. Because of the belief that post-operative deep vein thrombosis (DVT) is rare in Asian patients, thromboprophylaxis is not
usually prescribed for surgical patients. This study reports an open multi-centre controlled study of the use of a low molecular
weight heparin, nadroparin calcium (Fraxoparine Sanofi France), as opposed to no prophylaxis in 100 patients undergoing uncemented
total hip replacement. The patients had bilateral venography performed preoperatively and 10 days after operation. Eight patients
(16%) developed DVT in the control group of 50 patients and 1 (2%) in the treatment group, also of 50 patients. Pulmonary
embolus occurred in 1 patient in the treatment group and in 3 in the control group. Intraoperative and postoperative blood
loss did not differ significantly between the two groups. Our study suggests that the incidence of DVT in Asian patients,
though somewhat less than in their Western counterparts, is still considerable. It confirms the safety and efficacy of nadroparin
calcium in preventing post-operative DVT in patients undergoing elective total hip replacement.
Accepted: 19 March 1997 相似文献
Résumé. A cause de l’idée selon laquelle la thrombose veineuse profonde post-opéraloire est rare parmi les patients asiatiques, la tromboprophylaxie pour les patients opérés est inhabituelle. Nous avons accompli une étude, comparant la prophylaxie au moyen d’héparine de bas poids moléculaire en utilisant du calcium nadroparine (Fraxiparine Sanofi France) et la non-prophylaxie sur 100 patients subissant un remplacement total de la hanche. Les patients ont subi une vénographie bilatérale avant l’opération et 10 jours après. Huit patients (16%) ont développé une thrombose veineuse dans le groupe de contr?le, contre 1 (2%) dans le groupe traité (p = 0.015, 95% CI 0.02 – 0.67). Trois embolies pulmonaires sont survenues dans le groupe de contr?le et 1 dans le groupe traité (p = 0.27 95% CI 0.04 – 2.44) aucune n’étant fatale. La perte de sang intra-opératoire et post-opératoire n’a pas varié de manière significative entre les deux groupes. Notre étude démontre que l’incidence de la thrombose veineuse profonde post-opératoire chez les patients asiatiques est notable bien qu’elle soit moindre que dans les pays occidentaux et confirme la s?reté et l’efficacité du calcium nadroparine pour la prévenir aprés un remplacement total de la hanche.
Accepted: 19 March 1997 相似文献
145.
Two new nitro analogs of tranylcypromine, (E)-2-(p-nitrophenyl)cyclopropylamine ((E)-p-NTCP) and (E)-2-(m-nitrophenyl)cyclopropylamine ((E)-m-NTCP) were synthesized in order to examine the effect of aromatic nitro substitution on the MAO-inhibitory activity of 2-phenylcyclopropylamines. The compounds were obtained by treatingt-butyl (E)-2-(p-nitrophenyl) cyclopropanecarbamate andt-butyl (E)-2-(m-nitrophenyl)cyclopropanecarbamate withp-toluenesulfonic acid in CH3CN. Inhibitions of rat brain mitochondrial MAO-A and B by the compounds were examined using serotonin and benzylamine as the substrate at bothin vitro andex vivo levels. It was found fromin vitro measurements that(E)-p-NTCP at 6.0×10?5M elicited merely 22.5% inhibition against MAO-B without any effect on MAO-A. In contrast,(E)-m-NTCP showed fair degrees of inhibitions of MAO-A and B with IC50 values, 2.5×10?7M and 1.4×10?6M, respectively. It was also noted from(E)-m-NTCP thatm-nitro substitution caused a shift of selectivity of the inhibition toward MAO-A. According toex vivo measurements at 1.5, 3, 6, and 12 hr following the administration of a dose of 0.015 mmol/kg, i.p. to the rats, the inhibition percents of MAO-A by(E)-m-NTCP were 58.6, 63.7 63.6, and 46.6%, slightly lower than those observed by tranylcypromine. Whereas,(E)-p-NTCP at the same dose level did not show significant inhibitions against both MAO-A and MAO-B. Possible reasons for the difference in potencies between(E)-m-NTCP and(E)-p-NTCP were sought in relation to differing electron withdrawing effects ofm-andp-substituents which will influence electron density of the side chain amino functions and the partitions. 相似文献
146.
目的 探讨胃癌根治术术后肺部并发症(PPCs)的相关危险因素,为PPCs的个体化防治提供相应的对策。 方法 回顾性分析2019年1月至2021年3月兰州大学第二医院普通外科443例胃癌患者的临床资料,统计患者的临床病理特征,采用二分类Logistic回归分析胃癌根治术PPCs的危险因素。 结果 443例胃癌根治术PPCs的发生率为18.1%(80/443),其中肺部感染的发生率为12.4%(55/443),胸腔积液的发生率为11.7%(52/443),发生PPCs较未发生PPCs住院时间延长。Logistic回归分析显示,年龄≥60岁(OR=0.424、95%CI: 0.241~0.746)、糖尿病史(OR=0.318、95%CI: 0.146~0.693)、每分钟最大通气量(MVV)(%)<85%(OR=0.509、95%CI: 0.297~0.874)、术中失血量≥200 mL(OR=0.496、95%CI: 0.276~0.797)和术后吻合口并发症(OR=4.038、95%CI: 1.250~13.049)是胃癌根治术发生PPCs的独立危险因素。 结论 对于年龄≥60岁、糖尿病史、MVV(%)<85%、术中失血量≥200 mL、术后吻合口并发症的胃癌患者,应注意预防PPCs的发生。 相似文献
147.
摘要:糖尿病肾病是终末期肾病的主要病因。肾小球滤过屏障损伤导致的高蛋白尿是糖尿病肾病的主要特征,而足细胞功能及其结构的完整性对于肾小球滤过屏障至关重要。造成足细胞损伤的因素复杂且相互串扰,该文从糖脂代谢异常、氧化应激、慢性炎症、自噬、表观遗传学变化等角度阐释糖尿病肾病中足细胞的损伤机制,以期为糖尿病肾病的发生发展机制探讨、治疗及预后预测奠定理论基础。 相似文献
148.
Direct visualization and cellular localization of D1 and D2 dopamine receptors in rat forebrain by use of fluorescent ligands. 总被引:2,自引:1,他引:1
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M A Ariano F J Monsma Jr A C Barton H C Kang R P Haugland D R Sibley 《Proceedings of the National Academy of Sciences of the United States of America》1989,86(21):8570-8574
The regional and cellular localization of the two subtypes of dopamine receptors, D1 and D2, have been ascertained in rat forebrain by use of fluorescent dopaminergic antagonist ligands. (R,S)-5-(4'-aminophenyl)-8-chloro-2,3,4,5-tetrahydro-3- methyl-[1H]-3-benzazepin-7-ol, the 4'-amino derivative of the high-affinity D1-specific antagonist SCH 23390, and the D2 selective antagonist N-(p-aminophenethyl)spiperone were chemically derivatized using the fluorescent compound tetramethylrhodamine. The modification of these antagonist ligands has allowed the specific, cellular resolution of the D1 and D2 receptor binding sites in intact, highly organized regions of forebrain slices in a very rapid experimental time frame. The regional localization of receptors labeled by the fluorescent probes is in agreement with previous receptor autoradiography studies. Moreover, the specific cellular binding patterns for both receptors can now be compared and contrasted to one another in the same tissue by using these fluorescent ligands. D1 receptor sites are most evident within the striatum and exhibit regions of intense "patch" fluorescence corresponding to receptor reactivity in cells and their processes. The distribution of D1 receptor binding is highly analogous to the pattern of dopamine terminal histofluorescence in the caudate nucleus. D2 receptor sites are less prevalent overall and may be localized to a subpopulation of the D1 fluorescent neurons in the caudate nucleus and nucleus accumbens regions. 相似文献
149.
150.
Multiplex PCR for the detection of genes encoding aminoglycoside modifying enzymes and methicillin resistance among Staphylococcus species 总被引:4,自引:0,他引:4
Choi SM Kim SH Kim HJ Lee DG Choi JH Yoo JH Kang JH Shin WS Kang MW 《Journal of Korean medical science》2003,18(5):631-636
We developed multiplex polymerase chain reaction (PCR) to detect aac(6 ')/aph(2 "), aph(3 ')-IIIa, and ant(4 ')-Ia, the genes encoding the most clinically relevant amino-glycoside modifying enzymes (AME), and simultaneously, the methicillin resistant gene, mecA, in Staphylococcus species. Clinical isolates of 45 S. aureus and 47 coagulase negative staphylococci (CNS) from tertiary university hospitals were tested by conventional susceptibility testing, using the agar dilution method and by multiplex PCR. Of a total of 92 isolates, 61 isolates were found to be methicillin-resistant. Of these, 54 isolates (89%) were found to be harboring mecA. Seventy-five percent of the 92 isolates demonstrated resistance to at least one of the aminoglycosides tested. Moreover, resistance to aminoglycosides was closely associated with methicillin-resistance (p<0.05). The most prevalent AME gene was aac(6 ')/aph(2 ") which was found in 65% of the isolates, and ant(4 ')-Ia and aph(3 ')-IIIa were present in 41% and 9% of the isolates, respectively. The concordance between methicillin-resistance and the presence of mecA gene was 98% in S. aureus and 81% in CNS. The concordance between gentamicin resistance and the presence of aac(6 ')/aph(2 ") gene was 100% in S. aureus and 85% in CNS. The multiplex PCR method that we developed appears to be both a more rapid and reliable than conventional method. 相似文献