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71.
The B cell functional response following ligation of surface(s) lgM is dependent upon the differentiation stage of the populationstudied: cross-linking slgM promotes proliferation of restingtonsillar follicular mantle (FM) B lymphocytes but induces apoptosisin the susceptible Epstein- Barr virus genome-negative Burkittlymphoma (BL) cell line Ramos (Ramos-BL). This study investigateswhether phosphatidylinositol-3-kinase (Pl3-kinase), which hasbeen reported to be intimately involved in the regulation ofcellular growth, plays a role in the regulation of these sig-promoted B cell responses, and uses the selective and irreversibleinhibitor of Pl3-kinase activity, wortmannin (Wm). In Ramos-BLB cells, at 8 h post-treatment, Wm triggers a transient increasein apoptosis of 16 ± 6.9% with a concomitant cellularloss of 16 ± 6.1% from the G1 phase of cell cycle; [3H]thymidineincorporation also decreases by 33 ± 5.0%, from 37,274c.p.m. ± 10% to 25,127 c.p.m. ± 4.0%. Moreover,at 72 h culture, Wm inhibits anti-lgM-induced FM B lymphocytelevels of [3H]thymidine incorporation typically by 47% and triggers80% apoptosis from the G0G1 phase of cell cycle. Ramos-BL Bcells exhibit high basal levels of Pl3-kinase activity, as determinedby immunoprecipitation with antibody to the p85 regulatory subunitof Pl3-kinase and 32P incorporation into phosphatidylinositol,which is not significantly affected by anti-lgM stimulation;by contrast, anti-lgM stimulates significant Pl3-kinase activityover negligible basal levels in FM B lymphocytes. Pre-treatmentwith Wm inhibits Pl3-kinase activity in both cell types. Takentogether these data indicate that in Ramos-BL B cells slgM-triggeredgrowth arrest and apoptosis is Pl3- kinase independent, whereasPl3-kinase activity is critical for slgM-triggered mitogenesisof FM B lymphocytes. Thus Pl3-kinase plays a pivotal role inthe regulation of both normal and neoplastic B lymphocyte progressionthrough the cell cycle, such that if this Pl3-kinase-dependentpathway is inhibited these cells default to apoptosis. 相似文献
72.
王伏虎 《南京医科大学学报(英文版)》2002,16(2):49-64
Stroke is a debilitating disease that affects millions each year.While in many cases cerebral ischemic in jury can be limited by effectivw resuscitation or thrombolytic treatment,the injured neurons wither in a process known as delayed neuronal death(DND).Mounting evidence indicates that DND is not simply necrosis played out in slow motion but apoptosis is triggered.Of particular interest are two groups of signal proteins that participate in apoptosis-cyclin dependent kinases(CDKs) and p53-among a myriad of signaling events after an ischemic insult.Recent investigations have shown that CDKs,a family of enzymes initially known for their role in cell cycle regulation,are activated in injured neurons in DND.As for p53,new reports suggest that its up-regulation may represent a failed attempt to rescue in jured neurons,although its up-regulation was previously considered an indication of apoptosis.These observations thus rekindle an old quest to identify new neuroprotective targets to minimize the stroke damage.In this review,the author will examine the evidence that indicates the participation of CDKs and p53 in DND and then introduce pre-clinical data to explore CDK inhibition as a potential neuroprotective target.Finally,using CDK inhibition as an example,this paper will discuss the pertinent criteria for a viable neuroprotective strategy for ischemic in jury. 相似文献
73.
What is the value of bcl-2 protein detection for histopathologists? 总被引:15,自引:0,他引:15
74.
75.
目的应用基因芯片研究三氧化二砷(As2O3)处理前后K562细胞基因表达的变化.方法提取As2O3处理前后K562细胞的总RNA,纯化为mRNA后再反转录为cDNA.cDNA经限制性内切酶Sau3AI切割后,cDNA片段分别用Cy3和Cy5标记,与自制的包含348个基因片段的胎盘库芯片杂交.结果杂交结果经扫描和软件分析,发现了11个差异表达的基因片段,其中有3个基因片段与细胞凋亡密切相关.结论我们构建的胎盘库基因芯片可以成功地用于研究药物作用前后基因表达的变化. 相似文献
76.
电子直线加速器照射对NIH 3T3细胞的细胞周期及凋亡的影响 总被引:5,自引:0,他引:5
目的 探讨电子直线加速器照射对细胞周期及细胞凋亡的影响。方法 采用直线加速器对NIH 3T3细胞进行照射,观察细胞周期及细胞凋亡的改变情况;同时测定损伤前后p53蛋白的表达情况。结果 照射后细胞凋亡数增加,p53蛋白表达量上升。结论 电子直线加速器照射损伤可诱导细胞凋亡。 相似文献
77.
硒对紫外线诱导HLF细胞凋亡的保护作用 总被引:3,自引:1,他引:2
目的:探讨紫外线诱导人HLF细胞凋亡时DNA降解特点,以及硒对紫外线诱导细胞凋亡的保护作用。方法:紫外线分别照射体外培养的人肺成纤维细胞3min和5min,同时添加亚硒酸钠(8ng/ml),设立对照组。利用吖啶橙荧光染料染色鉴定凋亡细胞,利用琼脂糖凝胶电泳检测DNA ladder。结果:紫外线可以诱导人肺成纤维细胞(28代)凋亡,作用存在时间效应关系。紫外线诱导人肺成纤维细胞凋亡时,未出现典型的DNA ladder现象。硒对于紫外线诱导的细胞凋亡有显著的抑制作用。结论:DNA ladder不能作为细胞凋亡的唯一的标志,紫外线诱导的细胞凋亡与DNA ladder的出现并不总是一致的。硒具有拮抗紫外线诱导的细胞凋亡作用。 相似文献
78.
On the Role of Proteasomes in Cell Biology and Proteasome Inhibition as a Novel Frontier in the Development of Immunosuppressants 总被引:2,自引:0,他引:2
Jiangping Wu 《American journal of transplantation》2002,2(10):904-912
The proteasome, a large protease complex in cells, is the major machinery for protein degradation. It was previously considered a humble garbage collector, performing housekeeping duties to remove misfolded or spent proteins. Until recently, the interests of immunologists in proteasomes were focused largely on its role in antigen processing. Its real importance in cell biology has only been revealed contemporarily due to the availability of relatively specific inhibitors. It has now become increasingly clear that many aspects of immune responses highly depend on proper proteasome activity. Recently, a proteasome inhibitor has been successfully used to prevent acute as well as ongoing heart allograft rejection in mice. Such inhibitors are also efficacious in treating several autoimmune diseases, such as arthritis, psoriasis, and probably type I diabetes, in animal models. Phase II and III clinical trials of proteasome inhibitors in treating various tumors have shown promising results, and the side-effects of these drugs are tolerable. Therefore, proteasome inhibition represents a new and promising frontier in immunosuppressant development. 相似文献
79.
PGA指数和透明质酸在诊断慢性乙肝肝纤维化中的价值 总被引:1,自引:0,他引:1
目的:寻找一种简便实用的诊断慢性乙型肝炎纤维化的方法。方法:以78例经肝穿刺病理证实的慢性乙型肝炎为对象,测定并比较了由PT、GGT、ApoA1组成的PGA指数和HA、LN、PⅢP、C-IV与肝内纤维化程度(S)和炎症活动度(G)的关系。结果:(1)LN、PⅢP、C-IV在轻度慢性乙肝时无明显升高,在中度慢性乙肝时明显高于正常,但与轻度慢性乙肝无差异,而PGA指数和HA不仅在轻度慢性乙肝时显著升高,而且在轻中度间差异明显.因重度慢性乙肝和活动性肝硬化时,五项指标均显著增高。(2)在G2-4期,HA、LN、PⅢP、C-IV均明显高升,但在G1期,只有PGA指数高于正常,且各期间差异显著。(3)在S1-2期,只有PGA指数、HA、C-IV明显上升,但C-IV的上升幅度远低于PGA指数和HA。(4)加以PGA>4.5或HA>200μg/L作为判断临界值,则两者判断肝纤维化的敏感性均>94%,精确性>91%,特异性>86%,如两者结合,则分别达到98.3%、95.2%和96.4%。结论:PGA指数和HA均是反映慢性乙型肝炎患者肝内纤维化程度的良好指标,两者联合检测则可达到最大的价值效益比。 相似文献
80.
大鼠内毒素血症时外周血及肺泡内中性粒细胞死亡方式及呼吸爆发 总被引:2,自引:0,他引:2
本研究观察大鼠内毒素血症时肺组织中及外周血多形核中性粒细胞(PMN)凋亡,坏死及功能改变的差异。采用Wistar大鼠20只。腹腔注射LPS(O55B5,5mg/kg)造成内毒素血症,给予LPS后2,4,8,12小时(每组5只动物)取血及支气管肺泡灌洗,密度梯度法分离PMN,用流式细胞仪测定凋亡和坏死比例以及呼吸爆发功能的改变,同时采用5只大鼠作为正常对照。结果显示,内毒素血症时外周血和支气管肺泡灌洗液中PMN凋亡细胞比例相似。但与对照相比,外周血PMN坏死比例明显增加,呼吸爆发能力明显受抑,而支气管肺泡灌洗液PMN坏死比例显减少,呼吸爆发能力显增强。结论:在内毒素血症时,扣押于肺组织中的PMN在凋亡和坏死上表现出与比例显减少,呼吸爆发能力显增强,结论:在内毒素血症时,扣押于肺组织中的PMN在凋亡和坏死上表现出与外周血PMN不同的改变,其结果是组织中PMN存活增加,并持续处于活化状态,这与PMN造成组织损伤有关。 相似文献