不同原料制备乙型肝炎病毒特异性转移因子的研究

目的　为临床治疗乙肝提供一种安全、有效的免疫调节剂。方法　用组织匀浆、反复冻融破碎细胞、透析灭活和过滤除菌等技术 ,获得乙型肝炎病毒特异性转移因子 (HBV STF) ;用Lowry法测多肽含量 ;用苔黑酚显色法测定核糖核酸 (RNA)含量 ,用氨基酸分析仪分析测定HBV STF的水解氨基酸总含量。结果　来源于HbsAg阳性胎盘和HbsAg阳性血液的多肽含量分别为 0 4 9± 0 0 14和 0 2 9± 0 0 13(P <0 0 1) ,RNA含量分别为 0 34± 0 0 10和 0 2 2± 0 0 0 8(P <0 0 1)氨基酸总含量为 198 6± 1 5 6 2和 12 3 4± 1 5 2 1(P <0 0 1)。结论　用HbsAg阳性胎盘制备的乙型肝炎病毒特异性转移因子质量优于HbsAg阳性血液。     

卡维地洛对高血压大鼠主动脉的保护作用

目的 :研究卡维地洛对核因子 κB(NF κB)、单核细胞趋化蛋白 1(MCP 1)在自发性高血压大鼠 (SHR)大血管中表达的影响 ,探讨其对血管保护的机制。方法 :18只雄性 12周龄SHR随机分为阳性组 ,卡维地洛组 ( 30mg/kg·d) ,美托洛尔组 ( 50mg/kg·d) ,灌喂 8周 ;另选同龄雄性WistarKyoto大鼠为阴性组 (n =6 )。用免疫组化法测各组主动脉NF κB、MCP 1的表达 ,ELISA法测血清MCP 1含量。结果 :与阴性组比较 ,阳性组主动脉组织中NF κB、MCP 1表达增加 (P<0 .0 1) ,且两者正相关 (r=0 .72 8,P <0 .0 1) ;血清MCP 1含量升高 1.6 4(P <0 .0 1)。 8周后 ,治疗组之间血压无明显差异 (P >0 .0 5) ,但卡维地洛更显著抑制NF -κB、MCP 1表达 (P <0 .0 5)。结论 :卡维地洛可能独立于降压外抑制NF κB的活化来调控MCP 1表达。     

前S1蛋白在HBV指标中的重要意义

前S1蛋白是HBV衣壳蛋白的一部分，存在于大分子表面抗原蛋白之中，它是乙肝早期诊断的敏感指标，也反映了乙肝病毒的复制和乙肝病情的活动。本文研究显示，162例非乙肝病人血清中前S1蛋白全部阴性；311例乙肝患者中，前S1蛋白阳性率为38．9％，其中急性乙肝93．8％，慢性活动性肝炎51．2％，在乙肝二对半检测模式中，大三阳中该指标阳性率87．1％，小三阳为32．1％。以HBV DNA检测为标准，前S1蛋白的灵敏度为94．1％等，假阴性5．9％，总符合率93．9％。     

Ectopic T cell receptor expression causes B cell immunodeficiency in transgenic mice

Mice expressing transgenic T cell receptors (TCR) are used to explore important questions in immunity. However, transgene expression may have unexpected effects. We previously reported a B cell immunodeficiency, comprising decreased B cell numbers and diminished antibody responses, in mice that express a transgenic TCR specific for nicotinic acetylcholine receptor; the mice were generated using cassette vectors designed specifically for transgenic TCR expression [see Kouskoff et al. J. Immunol. Methods 1995. 180: 273-280]. We now show data suggesting that this defect is due to the expression and accumulation of TCR alpha and beta chains inside B cells and induction of an endoplasmic reticulum stress response, causing apoptosis at the pre B-I and later B cell stage. Thus, inappropriate transgene expression can profoundly affect B cells, leading to a previously undescribed mechanism of immunodeficiency.     

A phenotypic study of B lymphocyte subpopulations in human bone marrow.

The regulatory mechanisms that monitor the size of the peripheral B cell pool and determine cell death or survival are poorly understood. In rodents B lymphopoiesis is maintained at a high rate throughout adult life, and under resting conditions there is little recruitment into the long-lived peripheral pool; it therefore follows that most newly formed B lymphocytes have a very short lifespan. The maturation stages of B lymphopoiesis in humans and in experimental mammals appear to be similar. We have determined the phenotype of sIgM- and sIgD-expressing cells from normal adult human bone-marrow and peripheral blood by dual immunofluorescence with an extensive panel of monoclonal antibodies representative of major B cell clusters, in order to identify antigenic differences that may play a regulatory role. Antibodies of the CD21, CD22 and CD9 clusters, the unclustered restricted B antibody 7-F-7 and anti-IgD were reactive with different proportions of sIgM+ cells in blood and bone marrow; 29.5% (range 5-60%) of sIgM+ cells in marrow were sIgD- and most of these cells were also CD21- and CD22-, thus defining a unique marrow population. However, newly formed and mature re-circulating cells comprising the sIgM+sIgD+ population could not be distinguished by the panel of antibodies.     

银杏内酯B对体外培养乳鼠心肌细胞氧化损伤的保护作用

目的探讨银杏内酯B对体外培养乳鼠心肌细胞氧化损伤的保护作用及其机制.方法利用低浓度过氧化氢诱导原代培养乳鼠心肌细胞氧化损伤为模型,通过电镜观察细胞超微结构,以及培养介质中LDH活力,MDA含量,心肌细胞内Na -K -ATPase,GSH-PX活力的改变,来评价银杏内酯B对心肌细胞的保护作用,并探讨其机制.结果过氧化氢对心肌细胞有显著的损伤作用.银杏内酯B可使培养介质中的LDH和MDA水平显著下降,细胞内Na -K -ATPase,GSH-PX活力显著提高,同时细胞超微结构得到改普.结论银杏内酯B对过氧化氢致心肌细胞损伤有保护作用,机理与其抑制脂质过氧化和提高细胞内钠钾泵活力的作用有关.     

Decreased perforin and granzyme B expression in senescent HIV-1-specific cytotoxic T lymphocytes

Cytotoxic T lymphocyte (CTL) senescence may be an important mechanism of immune failure in HIV-1 infection. We find that senescence of HIV-1-specific CTL clones causes loss of killing activity, preventable by transduction with telomerase. Furthermore, senescence is associated with reduced expression of the effector molecules granzyme and perforin, suggesting CTL "exhaustion" can result in hypofunction. These results agree with other studies showing that HIV-1-specific CTL exhibit abnormal phenotypes in vivo, and suggest the possibility that chronic turnover is an important mechanism of antiviral failure in HIV-1 infection.     

ASODN对白细胞抗原Ⅰ类基因表达的影响

目的为观察针对乙型肝炎病毒（ＨＢＶ）ｘ基因特异性反义核酸（ＡＳＯＤＮ）对２２１５细胞表面白细胞抗原Ⅰ类基因（ＨＬＡ－Ⅰ）表达的影响。方法人工合成互补于ｘ基因关键区的三段反义核酸，用流式细胞仪检测ＡＳＯＤＮ对２２１５细胞表面ＨＬＡ－Ⅰ表达的影响，细胞原位杂交观察作用细胞内ＨＬＡ－ⅠｍＲＮＡ含量变化，同时用ＰＡＰ－ＥＬＩＳＡ法检测作用细胞上清中ＨＢｘＡｇ的含量。结果三段ＡＳＯＤＮ均能抑制ＨＢｘＡｇ的表达，２２１５细胞表面ＨＬＡ－Ⅰ类抗原的表达及细胞内ＨＬＡ－ⅠｍＲＮＡ含量也降低。结论ＨＢｘＡｇ表达量的降低可能系ＡＳＯＤＮ序列特异性抑制作用所致，而ＨＬＡ－Ⅰ表达的降低可能是ＨＢｘＡｇ对ＨＬＡ－Ⅰ基因启动子的激发减少的间接结果。     

EB病毒和ConA诱导抑制性T细胞对EB病毒感染B细胞作用探讨

本文探讨了用灭活的EB病毒(EBV)和ConA诱导产生的抑制性T细胞(Ts),对EBV感染自身B细胞的影响,结果表明,EBV抗原诱导产生的抑制性T细胞(Ts)能使EBV感染B细胞中的EBNA阳性细胞数,~3H-TdR掺入量和IgA、IgG及IgM分泌量减少;而ConA诱导产生的Ts则使EBNA阳性细胞数和~3H-TdR掺入量增加,但三种Ig含量无明显变化(P>0.05)。结果提示前者对EBV感染B细胞的激活,增殖和分化均有明显抑制作用,而后者的作用则相反,具有明显促进EBV感染B细胞的作用。     

受体选择与B细胞自身免疫耐受

基因重组机制的存在使得B细胞抗原受体呈现高度的多态性,这其中包括大量的自身反应性抗原受体;而免疫细胞在发育过程中对自身抗原耐受状态的形成正是为了避免对机体自身的攻击。传统认为这主要缘于自身反应性细胞或克隆的死亡性清除,即细胞选择;近年来随基因操作技术特别是转基因及基因靶导技术的成熟运用,发现这些被“清除”的细胞并非全部死亡,其中大部分是通过重新启动基因重组机制以一种“受体选择”(Receptor selection)的方式,以重组的新的非自身反应性受体替代了原自身反应性受体;同时受体选择尚参与成熟B特异性的调整,以使正参与免疫反应B细胞受体更加多样化从而适应当前免疫应答的需要。