Pharmacological Characterization of Bradykinin Receptors Coupled to Phosphoinositide Turnover in SV40-Immortalized Human Trabecular Meshwork Cells

This study sought to pharmacologically characterize bradykinin receptors on SV40-immortalized human trabecular meshwork (HTM3) cells. Phosphoinositide (PI) turnover studies were conducted using [³H]myo-inositol-labeled HTM3 cells and anion exchange chromatography to quantify [³H]inositol phosphates generated in response to bradykinin (BK) and various BK analogs. The blockade of these responses was studied using two potent and receptor-subtype selective antagonists. BK and T-kinin (Ile-Ser-BK; TK) induced a 4.2–4.4 fold stimulation of PI turnover above base levels at 1–10 μM. Several other peptides unrelated to BK, including angiotensin II, endothelin, cholecystokinin, bombesin and peptide YY tested at 1–10 μMwere essentially inactive. The molar potencies (EC₅₀) of BK, TK and close analogs were: BK=4.5±0.5 nM(n=6), Lys-BK=6.5±0.7 nM(n=3), TK=38.8±6.6 nM(n=8), Met-Lys-BK=41.5±13.4 nM(n=4), Des-Arg⁹-BK=2093±626 nM(n=4). All the latter BK-related peptides>were full agonists. The actions of BK and TK were potently and competitively antagonized by Hoe-140 (molar potency=0.6–1 nM;pA₂n=8.97–9.21,n=3–4) and byD-Arg⁰[Hyp³,-Thi^5,8,-DPhe⁷]-BK (molar potency=251 nM;-log potency, pK_b=6.6), two selective B₂-type BK antagonists. In conclusion, rank order of potency of BK agonists and the blockade of BK- and TK-induced PI turnover by the selective antagonists are consistent with the classification of the BK receptors on HTM3 cells as the B₂-receptor subtype.     

脑梗死患者血浆氧化低密度脂蛋白与一氧化氮、假性血友病因子及血浆颗粒膜蛋白的关系研究

目的探讨动脉粥样硬化性脑梗死患者血浆氧化低密度脂蛋白与血管内皮损伤及血小板活化程度的关系。方法用酶联免疫吸附测定（ELISA）的方法检测49例脑梗死患者和50例相匹配的对照组血浆氧化低密度脂蛋白（OX-LDL）、血管性假血友病因子（VWF）、血浆颗粒膜蛋白（GMP-140）水平，同时用硝酸还原酶比色法测定血清一氧化氮（NO）水平，并把、VWF、GMP-140、NO与OX-LDL作相关分析。结果脑梗死组血浆OX-LDL、、VWF、GMP-140明显高于对照组（t=2．91，P〈0．01；t=3．94，P〈0．001；t=2．08，P〈0．05），而脑梗死组血清NO水平明显低于对照组（t=4．02，P〈0．001）；相关分析表明血浆OX-LDL水平与血清NO水平呈负相关（r=-0．204，P〈0．05），与血浆懈呈正相关（r=0．60，P〈0．01），与血浆GMP-140呈正相关（r=0．430，P〈0．01）。结论脑梗死患者的血浆OX-LDL明显增高，而OX-LDL增高可能是脑梗死的危险因素。     

Priming B cell-mediated anti-HIV envelope responses by vaccination allows for the long-term control of infection in macaques exposed to a R5-tropic SHIV

The potential of vaccine-elicited anti-HIV envelope antibodies to control HIV-infection was evaluated by immunizing macaques with the HIV envelope protein and transiently depleting them of their CD8+ cells before intravenous challenge with the pathogenic CCR5-tropic SIV/HIV chimeric virus, SHIV(SF162P4). Although sterilizing immunity was not achieved, all vaccinated animals effectively controlled infection and remained free of disease for the duration of observation (over 3 years). In contrast, during the same period, the control animals progressed to disease. Both the vaccinees and the controls developed robust cell-mediated antiviral and neutralizing antibody responses following infection. A comparative analysis of these responses suggests that the more effective long-term control of infection by the vaccinated animals is due to the more rapid development of anti-HIV envelope antibodies. These studies suggest that priming by vaccination of B cell anti-HIV envelope responses maybe crucial for the long-term control of HIV infection.     

实验性犬心肌梗塞和溶栓后再闭塞时血浆中GMP—140,TXB2的变化

本文采用放免法测定实验性犬心肌梗塞和溶栓后再闭塞时血浆中ＧＭＰ－１４０、ＴＸＢ２、６－Ｋ－ＰＧＦ１α的含量变化，并探讨其与心肌梗塞溶栓后再闭塞的关系。结果表明，在血栓形成时血浆中ＴＸＡ２稳定代谢产物ＴＸＢ２水平显著升高（ｐ〈０．０５），在溶栓后再闭塞率高（８７．５％）的非治疗组（Ｂ组）。在溶栓后４小时至溶栓后３天期间呈进行性升高（ｐ〈０．０１），而在再 埘经低（１６．７％）的ＡＰＩ０１３４治疗组（     

冠脉循环中血小板活化状态对冠心病致病作用的研究

目的：探讨冠脉循环中血小板活化状态在冠心病（ＣＨＤ）发病学中的意义。方法：用放免等方法对受试冠状静脉窦（ＣＳ）及升主动脉（ＡＯ）血行血小板膜表面α－颗粒膜蛋白（α－ＧＭＰ－１４０）和循环内皮细胞（ＣＥＣ）等测定。结果：ＣＨＤ患冠脉循环中α－ＧＭＰ－１４０含量和ＣＥＣ浓度均明显升高（Ｐ〈０．０１）,以急心肌梗塞（ＡＭＩ）组为明显,冠脉狭窄愈严重,二升高愈明显,病灶多发比单发升高明显。结论：ＣＨＤ患冠脉循环中血小板高度激活,在ＣＨＤ的发生发展中有一定的意义。     

API0134对血小板α颗粒膜蛋白和血小板聚集的影响

２０例急性心肌梗死患者在溶栓后随机分为穿心莲有效成分（ＡＰＩ０１３４,ＡＰＩ）组与对照组,治疗１５ｄ,均同时给予阿司匹林等药物。检测溶栓前后血浆α颗粒膜蛋白（ＧＭＰ－１４０）浓度和ＡＤＰ诱导的血小板聚集反应。结果表明,ＡＰＩ组溶栓后７２ｈ血浆ＧＭＰ－１４０浓度轻度增加,对照组显著性增加（Ｐ＜０．０１）。ＡＰＩ组ＧＭＰ－１４０在溶栓后７２ｈ和１５ｄ均低于对照组,差异有显著意义（均为Ｐ＜０．０５）。ＡＰＩ组１ｍｉｎ和５ｍｉｎ血小板聚集率均低于对照组,差异均有显著意义（７２ｈ,Ｐ＜０．０５;１５ｄ,Ｐ＜０．０１）。研究表明,ＡＰＩ与阿司匹林联合应用可抑制溶栓后血小板的活化,优于阿司匹林单独应用,因此ＡＰＩ有可能用于临床预防溶栓后的再闭塞。     

血小板α颗粒膜蛋白140检测在“病”与“证的”特异性联系

应用血小板α颗粒膜蛋白１４０（ＧＭＰˉ１４０）为血小板活化指标，测定了７４例糖尿病、３６例心血管疾病、５３例肾脏疾病患者的血浆ＧＭＰˉ１４０浓度，并分别按病种及按是否有血瘀证分组比较了各组间的ＧＭＰˉ１４０测定值。结果表明：ＧＭＰˉ１４０在各疾病组患者均较正常人升高，三组间则无明显差异；而在血瘀及非血瘀证明之间则有明显差异。认为ＧＭＰˉ１４０有可能作为诊断血瘀证的一项实验室指标。     

人巨细胞病毒UL140基因在临床低传代分离株中的多态性研究

目的　研究人巨细胞病毒HCMV UL14 0基因在临床低传代分离株中的多态性及其与致病性的关系。方法　对 4 0株HCMV临床低传代分离株进行UL14 0基因全序列的PCR扩增 ,对 12株进行了测序及结果分析。结果　 4 0株HCMV UL14 0基因PCR扩增均阳性。测序的 12株HCMV UL14 0开放阅读框架 (ORF)均在Toledo株UL14 0 ORF的第 174位核苷酸处 ,插入一个胞嘧啶核苷酸C ,造成移码突变。与Toledo株相比 ,临床分离株新增了ScAMP磷酸化SPS和酪蛋白激酶Ⅱ磷酸化CKP两种重要功能位点 ,且其所位于的氨基酸位点可能是UL14 0蛋白的蛋白质作用位点。结论　临床分离株UL14 0基因的ORF较Toledo株多出 2 31个核苷酸 ,故两者的核苷酸及其编码产物氨基酸序列明显不同。临床分离株存在SPS及CKP两种新的重要功能位点 ,可能在HCMV UL14 0编码蛋白的生物学功能方面起重要作用。     

昆布多糖对家兔血小板聚集和释放的影响

目的 观察昆布多糖对家兔血小板聚集和释放的影响.方法 采用体内试验,比浊法观察昆布多糖对血小板活化因子(PAF)诱导的家兔血小板聚集作用的影响,双抗夹心放射免疫法测定血浆血小板颗粒膜蛋白(GMP-140)含量.结果 昆布多糖能抑制血小板活化因子诱导的家兔血小板聚集,与生理盐水组相比有显著差异(P＜0.05或P＜0.01),并能降低血小板颗粒膜蛋白含量(P＜0.01).结论 昆布多糖具有抗血小板活化因子诱导的血小板聚集作用,能抑制血小板的聚集和释放.     

心痛灵片对不稳定型心绞痛患者血小板活化功能的影响

目的:观察心痛灵片治疗不稳定性心绞痛的临床疗效及对血浆GMP-140的影响。方法:将64例中医辨证为气虚痰瘀阻络证不稳定性心绞痛患者,随机分为西药常规用药对照组和西药常规用药加心痛灵片治疗组进行临床观察。结果:治疗组中医临床证候改善、心绞痛缓解及心电图改善总有效率为90.63%、87.50%和75.00%,明显优于对照组(P<0.05)。经心痛灵片治疗后血浆GMP-140含量明显减少,与对照组比较有显著性差异(P<0.05)。结论:心痛灵片能改善血液凝集状态、延缓动脉粥样硬化进程,是治疗不稳定型心绞痛的有效药物,值得临床推广。