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1.
《Vaccine》2015,33(30):3440-3443
The differentiation of live attenuated vaccine strains from their progenitor and wild-type counterparts is important for ongoing surveillance of product safety and improved guidelines on their use. We utilised a genome sequencing approach to confirm that two cases of strangles in previously healthy horses that had received the Pinnacle I. N. vaccine (Zoetis) were caused by the vaccine strain. Our data shed new light on the safety of this vaccine and suggest that factors beyond the maturity of the animal's immune system influence the development of adverse reactions.  相似文献   
2.
目的 了解慢性HBV感染者HBeAg血清学转换后发生HBeAg逆转的流行病学特征,为推进慢性HBV感染者的规范管理提供依据。方法 2012-2014年对在江苏省传染病防治示范区建立的已发生HBeAg血清学转换的慢性HBV感染者队列开展定期随访。通过Cox回归分析慢性HBV感染者HBeAg血清学转换后HBeAg逆转的特征及影响因素,通过重复测量数据方差分析方法分析不同HBeAg转归者HBV DNA的变化趋势。结果 2012年5 068例已发生HBeAg血清学转换的慢性HBV感染者[平均年龄(51.9±12.8)岁]随访至2014年时121例发生HBeAg逆转,观察9 359人年,HBeAg逆转率为1.3/100人年。HBeAg逆转率随年龄增长逐渐降低,从<20岁年龄组的4.7/100人年下降至≥60岁年龄组的1.0/100人年。HBV DNA<2 000 IU/ml的感染者HBeAg逆转率为1.1/100人年,低于≥200 000 IU/ml者(3.8/100人年)。通过Cox多元回归分析,相对于HBV DNA<2 000 IU/ml者,HBV DNA≥200 000 IU/ml的感染者HBeAg逆转可能性增大(HR=3.44,95% CI:1.91~6.20,P=0.000)。HBeAg逆转组的HBV DNA和ALT较HBeAg持续阴性组均上升更快(P=0.000)。结论 社区人群中已发生HBeAg血清学转换的慢性HBV感染者有一定比例会发生HBeAg逆转,低年龄段和高病毒载量者的HBeAg逆转率高。对已发生HBeAg血清学转换的慢性HBV感染者应定期随访管理。  相似文献   
3.
It is unresolved whether recently transmitted human immunodeficiency viruses (HIV) have genetic features that specifically favour their transmissibility. To identify potential “transmission signatures”, we compared 20 full-length HIV-1 subtype C genomes from primary infections, with 66 sampled from ethnically and geographically matched individuals with chronic infections. Controlling for recombination and phylogenetic relatedness, we identified 39 sites at which amino acid frequency spectra differed significantly between groups. These sites were predominantly located within Env, Pol and Gag (14/39, 9/39 and 6/39 respectively) and were significantly clustered (33/39) within known immunoreactive peptides. Within 6 months of infection, we detected reversion-to-consensus mutations at 14 sites and potential CTL escape mutations at seven. Here we provide evidence that frequent reversion mutations probably allows the virus to recover replicative fitness which, together with immune escape driven by the HLA alleles of the new hosts, differentiate sequences from chronic infections from those sampled shortly after transmission.  相似文献   
4.
目的研究幽门螺旋杆菌(helicobacter pylori,Hp)感染对胃上皮细胞(GES-1)RECK基因启动子区域的甲基化以及mRNA表达水平的影响,并探讨其可能的致癌机制。方法用培养的Hp感染GES-1细胞0~144h。采用甲基化特异性聚合酶链式反应法检测RECK基因启动子区域的甲基化情况;逆转录PCR检测RECK基因mRNA水平;Westernblot检测核转录因子(NF-κB)的激活情况,并观察用NF-κB特异性抑制剂PDTC处理后的RECK的mRNA水平。结果 Hp感染GES-1细胞0~72h不能诱导RECK基因甲基化,感染96h后GES-1细胞内出现了明显的RECK基因甲基化,同时能降低RECK基因mRNA水平。Hp感染24h后能激活其NF-κB,24~72hNF-κB活性水平无明显改变。感染96h后NF-κB的活性有所增强,NF-κB特异性抑制剂PDTC能上调RECK基因的表达。结论 Hp感染通过诱导RECK基因启动子区域的甲基化,促进NF-κB激活,降低RECK基因的表达,这可能是Hp致胃癌的可能机制之一。  相似文献   
5.
目的探讨脑肿瘤干细胞(BTSCs)体外分化过程中的回逆现象,为研究其分化抑制机制奠定基础。方法利用CD133免疫磁珠筛选系统,从肿瘤组织中分离获得的CD133^+细胞(BTSCs)分成4组进行培养:(1)含10%胎牛血清(FCS);(2)10%FCS+丙戊酸钠注射液(VPA);(3)无FCS+生长因子;(4)无FCS+生长因子+VPA。取不同时间点上的细胞,相差显微镜观察其形态变化:流式细胞术检测与分化相关的标志物、细胞周期和DNA倍体变化;利用免疫激光共聚焦分析与分化相关标志物的共表达情况。结果无FCS条件下培养的BTSCs呈悬浮球状生长,高表达CD133和巢蛋白(nestin),不表达胶质纤维酸性蛋白(GFAP)和β-微管蛋白Ⅲ(β-TubulinⅢ)。G0/G1期细胞占大多数,G2/M期细胞接近0%,DNA都是异倍体,对VPA反应不敏感。含FCS培养的原本悬浮的细胞约4h开始贴壁。均呈圆形。此后逐渐向多形性分化,至7d时分化的细胞部分又返回至圆形。至10d-21d时,有的还能重新恢复球形,并呈悬浮生长。培养3d、7d、10d和21d时,CD133、nestin阳性细胞数先降后升,GFAP^+和β-TubulinⅢ^+细胞数始终处于较低水平。含FCS培养液中加入VPA。细胞形态上未见上述的回逆现象,CD133和nestin表达的先降后升现象消失,GFAP和β-TubulinⅢ在第7天以后表达明显升高,但极大部分细胞共表达nestin。而神经干细胞(NSCs)在含FCS培养至10d时,即以GFAP和β-TubulinⅢ表达为主,未见CD133^+细胞。此外,含血清培养时BTSCs仍以异倍体为主。含少量的G2/M期细胞,加VPA诱导后细胞周期和DNA倍体变化不明显。结论BTSCs在含血清条件下培养出现的多向分化表型不稳定,时有去分化所导致的回逆。加入诱导分化剂VPA培养,虽然能阻止回逆现象出现,并有代表星形胶质细胞和神经元标志物表达上升.但因其共表达nestin而仍属于未完全分化细胞,表明BTSCs分化始终处于受抑状态。  相似文献   
6.
Organ-cultured chick embryonic hearts of various ages. I. Electrophysiology   总被引:2,自引:0,他引:2  
Tetrodotoxin (TTX)-insensitive slow Na+ channels are converted or replaced by TTX-sensitive fast Na+ channels during normal embryonic development of the chick heart, and rapid reversion occurs in monolayer cell culture (denervated). Fast Na+ channels first appear at 4 to 5 days, which is about the time of innervation. Studies were done to determine whether changes in cation channels will occur while hearts are in organ culture. To test whether fast Na+ channels will develop in the absence of innervation, hearts from chick embryos 2 to 3 days old were placed into culture for 6 to 8 days. Although the resting potentials of the ventricular cells were about the same as those obtained from fresh 8 to 10 day old hearts, the maximum rate of rise of the action potentials (+ V?max) did not reach the high value (about 80 V/s) expected from the calendar age. Instead + V?max remained at about the same value (12 V/s) that the hearts had when placed into culture. The action potentials were completely insensitive to TTX. The slow channels admit primarily Na+ and not Ca2+ because Mn2+ (1 mm) and lowering [Ca2+]0 to nearly zero by EGTA did not diminish + V?max. To test whether the fast Na+ channels disappear in organ culture, hearts from embryos 15 to 19 days old were cultured as whole hearts or minced hearts. The whole hearts survived well for 1 to 6 days; the + V?max values remained high (~ 100 V/s), and TTX completely blocked the action potentials. The minced hearts had variable + V?max values, depending on the piece. Those pieces which had a low + V?max were insensitive to TTX, and those which had a high or intermediate + V?max, were reduced to 5 to 20 V/s by TTX; these persisting responses in TTX were not blocked by Mn2+ or zero [Ca2+]0. The results suggest that, while in organ culture, young hearts do not gain fast Na+ channels or lose the slow Na+ channels that would normally occur in situ. Organ-cultured old hearts left intact do not lose their fast Na+ channels. Thus, young or old hearts retain the channels that they originally possessed when placed into culture. Mincing initiates a gain of slow Na+ channels, and in some pieces, a partial loss of fast Na+ channels.  相似文献   
7.
8.
目的 :观察冠心病急性心肌梗死患者心肌纤维化的血清指标变化和血管紧张素转换酶抑制剂对心肌纤维化及心室重构的逆转作用 ,探讨血清指标作为临床判断心肌纤维化与心室重构及其逆转的临床价值。方法 :正常对照组20例 ,心肌梗死组44例 ,心肌梗死后应用培哚普利治疗12周 ,用放射免疫分析法测定血清指标PCⅢ (Ⅲ型前胶原 )、LN(层粘连蛋白 )、HA(透明质酸 )。结果 :心肌梗死2周后较正常对照组血清PCⅢ、LN、HA明显增高 (P<0 01) ,培哚普利治疗12周后血清PCⅢ、LN、HA明显下降 (P<0 01)。结论 :血清PCⅢ、LN、HA可以作为心肌梗死后心肌纤维化与心室重构的间接观察指标。  相似文献   
9.
目的:探讨超常规肾上腺素与氨茶碱合用在抢救心跳骤停中的临床机制。方法:选择86例不同疾病的心跳骤停患者,根据心跳停止时间不同分成5组,入院后立即静脉注射肾上腺素lmg/次,无效改为3mg/次,并与氨茶碱0.25-0.5g合用,无效追加肾上腺素为5mg/次,氨茶碱剂量同前,间隔3—5分钟,记录复苏例数,计算百分比。结果:心跳停止时间l-5分,6-10分,ll-15分给予肾上腺素lmg静脉注射,心跳恢复分别为34.6%、18.2%、13.3%;肾上腺素3mg静脉注射并合用氨茶碱,心跳恢复分别为64.7%、66.2%、46.2%;肾上腺素5mg静脉注射并合用氨茶碱,心跳恢复分别为50%、33.3%。结论:超常规剂量肾上腺素并合用氨茶碱对提高复苏成功率疗效肯定,且与心跳骤停时间有关。  相似文献   
10.
Mutagenic and antimutagenic properties of essential oil (EO) of basil and its major constituent Linalool, reported to possess antioxidative properties, were examined in microbial tests. In Salmonella/microsome and Escherichia. coli WP2 reversion assays both derivatives (0.25–2.0 μl/plate) showed no mutagenic effect. Salmonella. typhimurium TA98, TA100 and TA102 strains displayed similar sensitivity to both basil derivatives as non-permeable E. coli WP2 strains IC185 and IC202 oxyR. Moreover, the toxicity of basil derivatives to WP2 strains did not depend on OxyR function. The reduction of t-BOOH-induced mutagenesis by EO and Linalool (30–60%) was obtained in repair proficient strains of the E. coli K12 assay (Nikoli?, B., Stanojevi?, J., Miti?, D., Vukovi?-Ga?i?, B., Kne?evi?-Vuk?evi?, J., Simi?, D., 2004. Comparative study of the antimutagenic potential of vitamin E in different E. coli strains. Mutat. Res. 564, 31–38), as well as in E. coli WP2 IC202 strain. EO and Linalool reduced spontaneous mutagenesis in mismatch repair deficient E. coli K12 strains (27–44%). In all tests, antimutagenic effect of basil derivatives was comparable with that obtained with model antioxidant vitamin E. Linalool and vitamin E induced DNA strand breaks in Comet assay on S. cerevisiae 3A cells, but at non-genotoxic concentrations (0.075 and 0.025 μg/ml, respectively) they reduced the number of H2O2-induced comets (45–70% Linalool and 80–93% vitamin E). Obtained results indicate that antigenotoxic potential of basil derivatives could be attributed to their antioxidative properties.  相似文献   
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