血小板活化在运动所致心肌缺血中的临床意义

采用放射免疫法测定５５例冠心病患者和２０例健康人踏车试验（ＥＴ）前后血小板膜表面α－颗粒膜蛋白（ＧＭＰ－１４０）分子数和血浆血栓素Ｂ＿２（ＴＸＢ＿２）浓度变化。结果显示，冠心病组３６例ＥＴ阳性，１９例ＥＴ阴性，正常对照组２０例ＥＴ均阴性。冠心病ＥＴ阳性组运动后即刻血小板膜表面ＧＭＰ－１４０、血浆ＴＸＢ＿２较运动前明显升高（Ｐ＜０．０５）。冠心病ＥＴ阴性组和正常对照组运动前后血小板膜表面ＧＭＰ－１４０、血浆ＴＸＢ＿２差异无显著性（Ｐ＞０．０５）。提示血小板活化可能是运动所致心肌缺血的重要因素。     

血小板活化在不稳定性心绞痛中的意义

应用放免法测定３０例不稳定性心绞痛（ＵＡ）、２９例稳定性心绞痛（ＳＡ）患者和２０例正常人血小板膜表面α－颗粒膜蛋白（ＧＭＰ－１４０）分子数和血浆血栓素Ｂ２（ＴＸＢ２）浓度，结果显示，ＵＡ患者心绞痛发作时血小板膜表面ＧＭＰ－１４０及血浆ＴＸＢ２明显高于ＳＡ患者心绞痛发作时和正常对照组，后两者间差异无显著性。心绞痛终止后３０分钟，升高的ＧＭＰ－１４０全部恢复至正常组水平。ＧＭＰ－１４０显著增高者，易发生心肌梗塞和心脏性猝死。提示血小板活化在ＵＡ的发生和发展中具重要意义。     

经皮冠状动脉腔内成形术前后血小板功能及前列腺素水平的变 …

目的 研究冠心病患者经皮冠状动脉腔内成形术（ＰＴＣＡ）前后，冠状循环中血小板的变化，为临床用药提供参考，方法 由冠状静脉窦采血，采用放免方法检测ＰＴＣＡ术前血小板表面α－颗粒膜蛋白（ＧＭＰ１４０）分子数和血浆血栓素Ｂ２（ＴＸＢ２），血浆６－酮－前列腺素Ｆ１α（６－酮－ＰＧＦ１α）浓度。结果 ２３例稳定民绞痛患者，１５例不稳定心绞前患者ＰＴＣＡ术后５分钟血小板膜表面ＧＭＰ－１４０及血浆ＴＸＢ２明显增     

经皮冠状动脉腔内成形术前后血小板功能及前列腺素水平的变化及其临床意义

目的研究冠心病患者经皮冠状动脉腔内成形术（ＰＴＣＡ）前后，冠状循环中血小板的变化，为临床用药提供参考。方法由冠状静脉窦采血，采用放免方法检测ＰＴＣＡ术前后血小板表面α－颗粒胰蛋白（ＧＭＰ－１４０）分子数和血浆血栓素Ｂ２（ＴＸＢ２）、血浆６－酮－前列腺素Ｆ１α（６－酮－ＰＧＦ１α）浓度。结果２３例稳定心绞痛患者，１５例不稳定心绞痛患者ＰＴＣＡ术后５分钟血小板膜表面ＧＭＰ－１４０及血浆ＴＸＢ２明显增高，术后１０分钟达到高峰，３０分钟降至正常。结论冠心病患者ＰＴＣＡ术后确有血小板活化。     

糖尿病患者血小板功能的变化及其意义

采用放射免疫分析法检测了３０例正常人（对照组）及６８例糖尿病患者（糖尿病组）的血小板α－颗粒膜蛋白（ＧＭＰ－１４０）、血浆血栓素Ｂ２（ＴＸＢ２）、６－酮－前列腺素Ｆ１α（６－酮－ＰＧＦ１α）。结果糖尿病组血小板ＧＭＰ－１４０、ＴＸＢ２明显升高，６－酮－ＰＧＦ１α降低。表明糖尿病患者体内存在血小板的活化，且血小板功能的发迹与糖尿病微血管病变的发生、发展有关。     

急性心肌梗塞患者血小板膜表面抗人活化血小板α颗粒膜蛋白血浆凝血噁烷B_2、6－酮－前列腺素F_（1α）的动态变化及其临床意义

采用血小板膜表面抗人活化血小板α颗粒膜蛋白（ＧＭＰ－１４０）单克隆抗体ＳＺ－５１，以放射免疫法，检测２４例急性心肌梗塞（ＡＭＩ）患者发病１周内的血小板膜表面ＧＭＰ－１４０、血浆凝血烷Ｂ_２（血栓素Ｂ_２，ＴＸＢ_２）和６－酮－前列腺素Ｆ_（１α）（６－ｋｅｔｏ－ＰＧＦ_（１α））的动态变化，并与２０例健康人对照。ＡＭＩ的ＧＭＰ－１４０、ＴＸＢ_２和６－ｋｅｔｏ－ＰＧＦ_（１α）在发病早期已明显增高，４８ｈ达高峰，以后呈逐渐下降的规律性变化，这表明ＡＭＩ早期，血小板高度活化。ＴＸＢ_２和６－ｋｅｔｏ－ＰＧＦ_（１α）与ＧＭＰ－１４０正相关。梗塞范围广、病情重时，这三项指标增高更为显著。这提示，检测上述指标对监护病情，以及评估预后可能有辅助参考价值，并为发病早期选用抗血小板活性药物提供了客观依据。     

小儿急性白血病血小板活化的研究

采用单抗放免疫法测定５２例急白患儿和１８例健康儿童的血小板膜表面ＧＭＰ－１４０分子数和血浆ＴＸＢ２浓度显示，患儿ＧＭＰ－１４０和ＴＸＢ２明显高于健康儿童，Ｐ值分别〈０．００１和〉０．０１。各类型急白间差异不明显，经化疗随病情缓解而降至正常对照组水平，伴显性出血和化疗无效者ＧＭＰ－１４０和ＴＸＢ２均较高。     

糖尿病患者血管病变与血小板活化功能状态的关系

测定了７０例糖尿病（ＤＭ）患者的血小板活化状态指标（血小板ＧＭＰ－１４０、血浆ＴＸＢ２、血浆６－酮－ＰＧＦ１α），并一３０例健康人做对照。结果ＤＭ有血管病变者（ＤＭＩ组），的血小板ＧＭＰ－１４０、血浆ＴＸＢ２明显高于对照组，及无血管病变者（ＤＭⅡ组，Ｐ〈０．０５）；血浆６－酮－ＰＧＦ１α明显低于对照组，提示ＤＭ患者体内血小板处于活化状态，且此变化在血管病变发生前即已出现，血管病变发生后更为明显，其     

急性心肌梗塞血小板α－颗粒膜蛋白的改变及意义

采用抗人活化血小板α－颗粒膜蛋白（ＧＭＰ－１４０）单克隆抗体ＳＥ－５１测定了２６例急性心肌梗塞（ＡＭＩ）和２０例健康者血小板膜表面ＧＭＰ－１４０。发现ＡＭＩ患者起病后的１周内，ＧＭＰ－１４０呈动态变化，发病后６ｈ、２４ｈ即明显增高，４８ｈ达高峰，显著高于对照组，Ｐ值均＜００１。ＧＭＰ－１４０与同步测定之ＣＫ－ＭＢ峰值呈正相关。广泛心肌梗塞，伴严重心力衰竭、休克和严重心律失常者ＧＭＰ－１４０显著升高。结果表明，ＧＭＰ－１４０对ＡＭＩ的诊断、病情严重程度的评估都有帮助，并为选用抗血小板药物治疗提供了客观依据。     

急性凡肌梗塞血小板a—颗粒膜蛋白的改变及意义

采用伉人活化血小板ａ－颗粒膜蛋白单克隆抗体ＳＥ－５１测定了２６例急性凡肌梗塞和２０例健康者血小板膜表面ＧＭＰ－１４０。发现ＡＭＩ患者起病后的１周内，ＧＭＰ－１４０呈动态变化，发病后６ｈ，２４ｈ即明显增高，４８ｈ达高峰，显著高于对照组，Ｐ值均＜０．０１。ＧＭＰ－１４０与同步测定之ＣＫ－ＭＢ峰值呈正相关，广泛心肌梗塞，伴严重心力衰竭、休克和严重心律失常者ＧＭＰ－１４０显著升高，结果表明，ＧＭＰ－１４０     

miR-140靶向调控SOX2在结肠癌中的作用机制研究

目的 分析miR-140在结肠癌中的作用机制.方法 qRT-PCR检测miR-140在结肠癌细胞和组织中的表达;CCK8法、细胞划痕实验检测miR-140对结肠癌HT29细胞增殖和迁移的影响.TargetScan筛选miR-140的潜在靶基因并通过双荧光素酶报告基因试验进行验证;采用qRT-PCR和Western bl...     

Hepatitis B synthetic immunogen comprised of nucleocapsid T-cell sites and an envelope B-cell epitope.

Previous studies located T-cell recognition of the nucleocapsid of the hepatitis B virus (HBcAg) to residues 120-140 in mice bearing the H-2s or H-2b haplotypes. Herein, we demonstrate that B10.S (H-2s) and B10 (H-2b) H-2 congenic strains recognize distinct T-cell sites within the p120-140 (a synthetic peptide corresponding to residues 120-140 of HBcAg) sequence defined by p120-131 and p129-140, respectively. Peptide p120-131 stimulates B10.S HBcAg-primed T cells, and reciprocally p120-131-primed T cells recognize HBcAg. Similarly, the p129-140 sequence is a T-cell recognition site relevant to the native HBcAg in the B10 strain. It is also shown that these 12-residue peptides efficiently prime T-helper cells, which are capable of eliciting antibody production to HBcAg in vivo. These observations prompted us to examine the ability of the HBcAg-specific p120-140 sequence to function as a T-cell carrier moiety as a component of a totally synthetic hepatitis B vaccine. For this purpose a synthetic B-cell epitope from the pre-S(2) region (p133-140) of the viral envelope was chosen because this sequence represents a dominant antibody-binding site of the envelope. Immunization of B10.S and B10 strains with the synthetic composite peptide c120-140-(133-140) elicited anti-peptide antibody production, which was crossreactive with the native viral envelope. Furthermore, c120-140-(133-140) immunization primed p120-131-specific T cells in the B10.S strain and p129-140-specific T cells in the B10 strain, which recognized HBcAg and provided T-helper cell function for anti-envelope antibody production in vivo. These results demonstrate the feasibility of constructing complex synthetic immunogens that represent multiple proteins of a pathogen and are capable of engaging both T and B cells relevant to the native antigens.     

The prognostic significance of IDH2 mutations in AML depends on the location of the mutation

We have investigated the prognostic significance of isocitrate dehydrogenase 2 (IDH2) mutations in 1473 younger adult acute myeloid leukemia patients treated in 2 United Kingdom Medical Research Council trials. An IDH2 mutation was present in 148 cases (10%), 80% at R140 and 20% at R172. Patient characteristics and outcome differed markedly between the 2 mutations. IDH2(R140) significantly correlated with nucleophosmin mutations (NPM1(MUT)), whereas IDH2(R172) cases generally lacked other molecular mutations. An IDH2(R140) mutation was an independent favorable prognostic factor for relapse (P = .004) and overall survival (P = .008), and there was no significant heterogeneity with regard to NPM1 or FLT3 internal tandem duplication (FLT3/ITD) genotype. Relapse in FLT3/ITD(WT)NPM1(MUT)IDH2(R140) patients was lower than in favorable-risk cytogenetics patients in the same cohort (20% and 38% at 5 years, respectively). The presence of an IDH2(R172) mutation was associated with a significantly worse outcome than IDH2(R140), and relapse in FLT3/ITD(WT)NPM1(WT)IDH2(R172) patients was comparable with adverse-risk cytogenetics patients (76% and 72%, respectively).     

非瓣膜病心房颤动患者血小板活化状态的研究

目的了解非瓣膜病心房颤动(房颤)患者血小板的活化状态。方法观察92例非瓣膜病持续性房颤患者(房颤组)与60例窦性心律者(对照组)血小板功能状态的分子标记物水平,用酶联免疫吸附双抗体夹心法测定血浆血小板α颗粒膜糖蛋白-140(GMP-140)水平,用放射免疫分析法测定血栓素B2(TXB2)和6-酮-前列腺素F1α(6-k-PGF1α)水平。结果房颤组GMP-140和TXB2水平显著高于对照组,6-k-PGF1α水平显著低于对照组,TXB2/6-k-PGF1α比值也显著高于对照组。调整其他影响因素后,房颤组GMP-140和TXB2水平仍显著高于对照组,6-k-PGF1α水平仍显著低于对照组。GMP-140水平在合并糖尿病和合并高甘油三酯血症的房颤患者进一步升高。结论非瓣膜病房颤患者处于血小板激活状态。     

A small molecule inhibitor of mutant IDH2 rescues cardiomyopathy in a D-2-hydroxyglutaric aciduria type II mouse model

D-2-hydroxyglutaric aciduria (D2HGA) type II is a rare neurometabolic disorder caused by germline gain-of-function mutations in isocitrate dehydrogenase 2 (IDH2), resulting in accumulation of D-2-hydroxyglutarate (D2HG). Patients exhibit a wide spectrum of symptoms including cardiomyopathy, epilepsy, developmental delay and limited life span. Currently, there are no effective therapeutic interventions. We generated a D2HGA type II mouse model by introducing the Idh2R140Q mutation at the native chromosomal locus. Idh2R140Q mice displayed significantly elevated 2HG levels and recapitulated multiple defects seen in patients. AGI-026, a potent, selective inhibitor of the human IDH2R140Q-mutant enzyme, suppressed 2HG production, rescued cardiomyopathy, and provided a survival benefit in Idh2R140Q mice; treatment withdrawal resulted in deterioration of cardiac function. We observed differential expression of multiple genes and metabolites that are associated with cardiomyopathy, which were largely reversed by AGI-026. These findings demonstrate the potential therapeutic benefit of an IDH2R140Q inhibitor in patients with D2HGA type II.     

射频消融术对凝血、抗凝系统的影响及阿斯匹林的作用

为探讨射频消融术 (RFCA)后外周血管栓塞的发生机制 ,将 6 0例室上性心动过速患者分为两组 (A组术前不用抗凝药 ,B组术前使用阿斯匹林 (ASA) ,在术前、插管完成心内电生理检测后、RFCA后即刻及术后两天 4个时段抽静脉血观察血小板α 颗粒膜糖蛋白 (Gmp 140 )、血栓烷B2 (TXB2 )、蛋白C(PC)、蛋白S(PS)的变化。结果 :A组病人 ,与术前比较 ,其他 3个时段血浆Gmp 140、TXB2 含量明显增加 (分别为 7.32± 0 .49,12 .87± 1.99,13.6 4± 1.47pg/mlvs 6 .2 6± 0 .75pg/ml,P <0 .0 5或 0 .0 1;80 .0 6± 2 .18,10 0 .42± 1.41,90 .0 8± 4.82pg/mlvs 70 .45± 2 .2 7pg/ml,P <0 .0 5或 0 .0 1) ,PC及PS血浆含量无变化 ,但左右心系统操作对Gmp 140、TXB2 变化无影响 ;B组与A组相比 ,术后相同时段的血浆Gmp 140、TXB2 含量减小 ,P <0 .0 5或 0 .0 1。提示RFCA可引起血小板的激活 ,对抗凝系统无明显影响 ,可致血栓形成 ;服用ASA可阻止血小板的激活 ,从而阻止血栓形成的作用     

急性肺损伤患者血浆颗粒膜蛋白—140改变的临床意义

目的 :观察急性肺损伤 (ALI)患者血浆颗粒膜蛋白 140 (GMP 140 )及相关指标的改变 ,并探讨其临床意义。方法 :对 32例ALI患者进行多时间点检测血浆中GMP 140、循环内皮细胞(CEC)、内皮素 1(ET 1)和血管紧张素转换酶 (ACE)含量 ,并设健康对照组。结果 :肺损伤后 1h内 ,血中GMP 140、CEC、ET 1和ACE均显著升高并持续 8h ,血浆GMP 140早期升高 ,幅度较大 ,1h内 5 0 .5 6± 8.79μg/L ,较对照组16 .32± 4.5 1μg/L高 (>3倍 ) ,伤后 2h达高峰 (5 4.38± 9.94μg/L) ,各时间点与对照组比较 ,P均 <0 .0 1;并与其他指标有较好的相关性。结论 :血浆GMP 140可作为ALI患者的病情监测和评估的有用指标。     

D2S140基因多态性与2型糖尿病的相关性研究

目的：探讨D2S140基因多态性与2型糖尿病的关系。方法：运用聚合酶链反应（PCR）技术,结合短串联重复序列（STR）多态性标记的方法,检测了103例2型糖尿病患者和105例正常对照者的D2S140等位基因及基因型,结果：发现7种等 位基因。等位基因2与2型糖尿病呈显著性正相关（RR＝13。76,P＜0．001）,等位基因6与2型糖尿病呈显著性负相关（RR＝0．25,P＜0．001）。多因素非条件Logistic回归分析表明,D2S140等位基因2是2型糖尿病的独立危险因素,其相对危险度明显高于环境因素。结论：DS2S140基因多态性与中国人2型糖尿病相关。     

Expression and modification of PKA and AKAPs during meiosis in rat oocytes

Meiosis in oocytes is initiated during fetal life, arrested around birth and resumed after puberty. Meiotic arrest is controlled by a cAMP-dependent protein kinase (PKA)-mediated cAMP action. We examined oocytes for the presence and modulation of the regulatory (R) subunits of PKA and the A-kinase anchoring proteins (AKAPs) that target PKA to specific subcellular locations. We found that rat oocytes express the two regulatory subunit isoforms, RI and RII of PKA. Immunocytochemistry revealed that the regulatory subunits underwent cellular translocation upon resumption of meiosis. We also demonstrated the presence of a novel 140 kDa AKAP, AKAP140 that exhibited a retarded electrophoretic motility at reinitiation of meiosis. The mobility shift of AKAP140 was susceptible to alkaline phosphatase and prevented by inhibition of p34cdc2 kinase. We conclude that rat oocytes express AKAP140 that is phosphorylated during meiosis. AKAP140 phosphorylation is sensitive to p34cdc2 kinase inhibitors. We hypothesize that AKAP140 and its phosphorylation state may influence the translocation of the R subunits of PKA throughout resumption of meiosis.