Favorably tipping the balance between cytopathic and regulatory T cells to create transplantation tolerance

Therapeutic application of broadly reactive anti-T cell antibodies can lead not only to potent immunosuppression but also to profound and long-lived T cell depletion. We reasoned that a strategy that almost exclusively targets activated cytopathic donor reactive T cells and spares immunoregulatory networks might prove to be an exceptionally potent and highly selective means of producing long-term engraftment and tolerance. Herein we show that the combined administration of rapamycin and agonist IL-2- and antagonist IL-15-related cytolytic fusion proteins provides for long-term engraftment/tolerance in exceptionally stringent allotransplant models by (1) limiting the early expansion of activated T cells, (2) preserving and even exaggerating their subsequent apoptotic clearance, and (3) further amplifying the depletion of these activated T cells by antibody-dependent mechanisms, while (4) preserving CD4+CD25+ T cell-dependent immunoregulatory networks.     

Investigation of 89 candidate gene variants for effects on all-cause mortality following acute coronary syndrome

Background  

Many candidate genes have been reported to be risk factors for acute coronary syndrome (ACS), but their impact on clinical prognosis following ACS is unknown.     

司帕沙星对试验动物的一般药理研究

小鼠单次经口灌服司帕沙星4、20和100mg/kg后,动物的活动正常,未出现兴奋的抑制作用;小鼠单次经口灌服司帕沙星4、20和100mg/kg,与戊巴比妥钠镇静催眠无明显协同作用;给猫静脉注射司帕沙星4、16和64mg/kg,对动物呼吸和心血管系统无明显影响。     

Fas蛋白在糖尿病大鼠局灶性脑缺血再灌注损伤后海马区的表达及意义

目的探讨Fas蛋白在糖尿病大鼠脑缺血再灌注海马区神经元损伤中的表达及意义。方法健康雄性Wister大鼠60只,随机分为4组:①正常对照组,②假手术组,③脑缺血再灌注组(NIR),④糖尿病脑缺血再灌注组(DIR组);采用STZ诱导糖尿病和线栓法建立大脑中动脉闭塞(MCAO)模型,HE法观察海马CA1神经元缺失,用免疫组化方法检测Fas在糖尿病大鼠脑缺血再灌注海马神经元损伤中的表达。结果HE染色:正常对照与假手术组未见神经元缺失和细胞凋亡,DIR组与脑缺血再灌注组均见神经元缺失和神经细胞凋亡,而DIR组比脑缺血再灌注组神经元缺失严重(P<0.05)。正常对照与假手术组极少见Fas免疫染色阳性细胞,DIR组与脑缺血再灌注组明显见Fas免疫染色阳性细胞,且DIR组比脑缺血再灌注组多(P<0.05)。结论Fas介导的细胞凋亡可能是糖尿病脑缺血再灌注损伤后海马区神经元损伤的机制之一。     

DNA prime followed by protein boost enhances neutralization and Th1 type immunity against FMDV

Prime-boost strategy has been exhibited its potency to enhance immune responses, which would be important to the success to develop a vaccine against the foot-and-mouth disease virus (FMDV). An eukaryotic expression construct encoding the FMDV capsid VP1 protein with a recombinant VP1 protein or a commercial FMDV vaccine were tested in the prime-boost strategy in mice and cattle trials. The levels of induced specific antibodies, T cell proliferations, and DTH activities were significantly higher in the prime-boost groups than in those vaccinated with DNA, protein or FMDV vaccine alone. More importantly, the levels of neutralizing antibodies in the former groups were significantly higher than others and could last for at least four months in cattle trials. This study suggests that the prime-boost strategy significantly improves the effective immunity and may provide a longer protection against FMDV infection.     

CTT triplex系统各基因座位等位基因在葡萄胎基因组中的分布及其意义

我们对采用PCR和聚丙烯酰胺凝胶电泳鉴别出的37例DNA完全来自父方的遗传学完全性葡萄胎(g-CHM)进行基因组中CTTtriplex系统各基因座位(CSF1PO、TPOX和TH01)等位基因分布的分析,并初步研究了这些等位基因分布与临床预后的关系。结果显示,在37例g-CHM中,CSF1PO座位中3个等位基因(11,12和14)和TPOX座位中的1个等位基因(11)的出现率与它们在北京地区人群中的基因频率差异显著;g-CHM中CSF1PO、TPOX和TH01基因座位杂合度显著低于北京地区人群的杂合度(P值均远小于0.01);在23例良性g-CHM和10例侵袭性g-CHM中:CSF1PO座位的等位基因10、11在良性中的出现率高于在侵袭性g-CHM中(P=0.026148),等位基因12在良性中的出现率低于在侵袭性g-CHM中(P=0.023879);TPOX座位的等位基因8在良性中的出现率高于在侵袭性g-CHM中(P=0.004322),而等位基因11在良性中的出现率低于其在侵袭性g-CHM中(P=0.008671)。上述结果提示,葡萄胎基因组中存在某些等位基因分布与在人群中的分布不同,而且葡萄胎是否具有侵袭性也和某些等位基因的出现率过高或过低有相关性,这些与侵袭性有关的等位基因可能成为预测葡萄胎是否具有侵袭性的标志物。     

磷酸组织胺诱导的Ⅰ型超敏反应对肝损伤作用的研究

目的:通过观察与Ⅰ型超敏反应相关的生物活性介质--组织胺对家兔肝脏有无直接损伤作用,进一步论证Ⅰ型超敏反应对肝脏的损伤作用.方法:选择34只家兔随机分为对照组、实验Ⅰ组和实验Ⅱ组3组;对照组只进行正常饲料喂养,实验Ⅰ组在正常饲料喂养的同时每天给予0.4μg/kg耳静脉注射磷酸组胺注射液,实验Ⅱ组在正常饲料喂养的同时每天给予0.08 μg/kg耳静脉注射磷酸组胺注射液;动态观察以上3个组的血清谷丙转氨酶(ALT)及血清谷草转氨酶(AST)变化;利用光学显微镜观察以上3个组肝组织的病理变化.结果:无论是实验Ⅰ组或实验Ⅱ组,经过一段时间的观察,发现血清内ALT和AST含量均显着高于对照组(P＜0.01),但Ⅰ、Ⅱ组之间无显着性差异(P＞0.05);实验Ⅰ组和实验Ⅱ组在显微镜下观察,其肝脏均有不同程的损伤和病理改变,且实验Ⅱ组的损伤和变化大于实验Ⅰ组,而对照组的肝脏则无明显的病理变化.结论:组织胺对家兔肝脏确实有一定的损伤作用,而且随着投予剂量和时间的增加,肝脏的损伤和病理变化也越显著;通过本研究,可以得出Ⅰ型超敏反应导致肝脏病理变化及损伤的见解.     

肝毒清颗粒对大鼠实验性肝纤维化的防治作用

目的 :观察肝毒清颗粒的抗纤维化作用。方法 :将Wistar雄性大鼠随机分成 6组 ,即正常对照组、模型组、肝毒清大、中、小剂量组和乙肝宁阳性组 ,采用四氯化碳诱导肝纤维化模型。于造模第 2个月始给予治疗药物。实验持续 3月后将大鼠处死取血作肝功检查及取肝组织做病理检查。结果 :肝毒清能降低AST ,升高TP、ALB ,与模型组比较 (P <0 .0 5 ) ;减轻肝脂肪变性、减少纤维组织增生、促进肝细胞再生。结论 :肝毒清对大鼠肝纤维化有明显防治作用     

癫癎患者脑血流速度改变与癫癎灶定侧的关系

目的 :探讨癫发作间期脑血流变化对癫灶定侧的价值。方法 :4 7例癫病人发作间期行经颅多普勒超声脑血流速度测定 ,并与临床、脑电图定位和MRI/CT病灶对比分析。结果 :根据临床症状确定病灶侧的 19例病人中 ,病灶侧脑血流速度改变 (升高和降低 )的比率显著高于双侧脑血流速度对称者 ;在脑电图确定病灶侧的 2 4例病人中 ,病灶侧脑血流速度升高比率显著高于脑血流速度降低和双侧脑血流速度对称者 ;在MRI确定病灶侧的 13例病人中 ,病灶侧脑血流速度增快 7例 ,减慢 2例 ,双侧血流速度对称 4例。结论 :癫病人一侧脑血流速度增高 ,高度提示癫病灶侧。