SLE患者外周血淋巴细胞表达BLyS和CD86的变化

采用FACS研究了 2 2例SLE患者外周血淋巴细胞表达BLyS和CD86的变化。结果表明 ,SLE患者外周血BLyS 淋巴细胞和CD19 CD86 淋巴细胞显著增加 ,但二者之间无显著相关。     

Zn^2＋与苹果多酚氧化酶相互作用研究

为探讨苹果多酚氧化酶（简称PPO）的结构与功能关系,应用紫外差示光谱、同步荧光光谱及圆二色性光谱（CD）等生物物理技术和酶活性测定研究了外加Zn^2＋对苹果PPO的分子构象和酶活性的影响。结果表明,微景锌的加入能增加酶的活性和提高α-螺旋含量,当[Zn^2＋]／[PPO]为2．0左右时,苹果PPO活性最高,继续增加[Zn^2＋]／[PPO]比值,酶活性开始下降,比值为2．7以后,Zn^2＋表现了对PPO活性的抑制,α-螺旋含量下降;Zn（Ⅱ）可能与PPO中的组氨酸残基进行了配位,（ImH）σN＋σN→Zn^2＋、（ImH）σ→Zn^2＋、（ImH）π1→Zn^2＋、（ImH）Ⅱπ→Zn^2＋分别为227,241,265,335（nm）;色氨酸和酪氨酸的荧光均受到Zn^2＋的猝灭,但它们的微环境在Zn（Ⅱ）-PPO的相互作用中基本保持不变。     

Chemotherapy and immunotherapy of malignant glioma: molecular mechanisms and clinical perspectives

Despite the considerable progress in modern tumor therapy, the prognosis for patients with glioblastoma, the most frequent malignant brain tumor, has not been substantially improved. Although cytoreductive surgery and radiotherapy are the mainstays of treatment for malignant glioma at present, novel cytotoxic drugs and immunotherapeutic approaches hold great promise as effective weapons against these malignancies. Thus, great efforts are being made to enhance antitumoral efficacy by combining various cytotoxic agents, by novel routes of drug administration, or by combining anticancer drugs and immune modulators. Immunotherapeutic approaches include cytotoxic cytokines, targeted antibodies, and vaccination strategies. However, the success of most of these experimental therapies is prevented by the marked molecular resistance of glioma cells to diverse cytotoxic agents or by glioma-associated immunosuppression. One promising experimental strategy to target glioma is the employment of death ligands such as CD95 (Fas/Apo1) ligand or Apo2 ligand (TRAIL). Specific proapoptotic approaches may overcome many of the obvious obstacles to a satisfactory management of malignant brain tumors. Received 8 March 1999; received after revision 27 May 1999; accepted 14 June 1999     

Dexamethasone enhances CTLA-4 expression during T cell activation

T cell activation is enhanced by the costimulatory interaction of B7 on antigen-presenting cells and CD28 on T cells, resulting in long-term T cell proliferation, differentiation and production of large amounts of cytokines, such as interleukin (IL)-2. CTLA-4 is a co-stimulation receptor that shares 31% homology with CD28 and binds B7 family members with higher affinity. CTLA-4 is transiently expressed intracellularly and on the cell surface following activation of T cells. We have studied the kinetics of CTLA-4 expression and the effects of dexamethasone on CTLA-4 expression during T cell activation in cultures of mouse spleen cells stimulated by a mixture of immobilized anti-CD3 and anti-CD28 monoclonal antibodies (anti-CD3/CD28 mAb) or concanavalin A (ConA). CTLA-4 expression peaked on day 2 and returned to background levels after 7 days. Dexamethasone was found to potentiate CTLA-4 expression in a dose-dependent manner with an EC₅₀ effective concentration 50%) of about 10⁻⁸ M. In contrast, other immunosuppressive agents, such as rapamycin or cyclosporin A had no or an inhibitory effect on CTLA-4 expression, respectively. Dexamethasone also stimulated CD28 expression, but inhibited IL-2R expression during anti-CD3/CD28 mAb-induced mouse splenic T cell activation. Western blot analyses of lysates of activated mouse T cells showed that dexamethasone increased CTLA-4 protein levels twofold during anti-CD3/CD28 mAb-induced activation. Dexamethasone also enhanced CTLA-4 messenger RNA twofold as quantified by ribonuclease protection assay. The effects of dexamethasone on CTLA-4 expression were glucocorticoid-specific and completely inhibited by the glucocorticoid receptor antagonist mifepristone (RU486), indicating that the effect of dexamethasone on CTLA-4 expression is mediated through the glucocorticoid receptor. In conclusion, the immunosuppressive agent dexamethasone actually stimulates CTLA-4 expression, which is involved in downregulation of T cell activation. Received 19 May 1999; received after revision 13 July 1999; accepted 13 July 1999     

HAb18G/CD147-mediated calcium mobilization and hepatoma metastasis require both C-terminal and N-terminal domains

HAb18G/CD147 is a heavily glycosylated protein containing two immunoglobulin superfamily domains. Our previous studies have indicated that overexpression of HAb18G/CD147 enhances metastatic potentials in human hepatoma cells by disrupting the regulation of store-operated Ca²⁺ entry by nitric oxide (NO)/cGMP. In the present study, we investigated the structure-function of HAb18G/CD147 by transfecting truncated HAb18G/CD147 fragments into human 7721 hepatoma cells. The inhibitory effect of HAb18G/CD147 on 8-bromo-cGMP-regulated thapsigargin-induced Ca²⁺ entry was reversed by the expression of either C or N terminus truncated HAb18G/CD147 in T7721C and T7721N cells, respectively. The potential effect of HAb18G/CD147 on metastatic potentials, both adhesion and invasion capacities, of hepatoma cells was abolished in T7721C cells, but not affected in T7721N cells. Release and activation of matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were found to be enhanced by the expression of HAb18G/CD147, and this effect was abolished by both truncations. Thapsigargin significantly enhanced release and activation of MMPs (MMP-2 and MMP-9) in non-transfected 7721 cells, and this effect was negatively regulated by SNAP. However, no effects of thapsigargin or SNAP were observed in T7721 cells, and expression of HAb18G/CD147 enhanced secretion and activation of MMPs at a stable and high level. Taken together, these results suggest that both ectodomain and intracellular domains of HAb18G/CD147 are required to mediate the effect of HAb18G/CD147 on the secretion and activation of MMPs and metastasis-related processes in human hepatoma cells by disrupting the regulation of NO/cGMP-sensitive intracellular Ca²⁺ mobilization although each domain may play different roles.Received 1 April 2004; received after revision 15 June 2004; accepted 22 June 2004     

一种三项CD共轭梯度法及其全局收敛性

在前人提出的三项PRP共轭梯度法的基础上,提出了一种三项CD共轭梯度法.与以往求解无约束优化问题的经典二项共轭梯度法不同,该算法的搜索方向是三项的,且在任何线性搜索下都具有充分下降性.在适当的条件下,证明了三项CD共轭梯度法在强Wolfe线性搜索下具有全局收敛性.     

有机手性分子器件的光电特性

目前多种有机手性分子器件虽已研制成功,但其内在的物理机理仍有许多未解之谜,其中手性分子的圆二色性精细结构、手性诱导的自旋选择效应等是有机手性分子研究的核心.为设计基于手性的新型有机功能器件提供理论指导,考虑有机手性分子螺旋势场诱导的自旋-轨道耦合,围绕分子的光电特性及其调控展开了系列研究.根据光致跃迁理论,得到手性分子...     

HCV感染通过Erk信号的激活上调PTTG1的表达

 为探讨丙型肝炎病毒(HCV)感染导致肝细胞癌发生的分子机制,利用前期研究建立的体外HCV细胞培养体系,将HCV JFH-1 RNA转染CD81-Huh7细胞,确定能够获得感染性HCV后,收集HCV转染后10,50,100和150d的细胞,采用Real time PCR及Western Blot法检测不同时间点细胞内垂体瘤转化基因1(PTTG1)基因和蛋白水平的表达情况,同时检测总MAPK/Erk1/2,磷酸化Erk1/2(p-Erk1/2)蛋白的表达。随后,用干扰素抑制HCV的感染,再检测PTTG1及MAPK/Erk1/2的表达情况,以及用MAPK/Erk抑制剂(PD98059)阻断MAPK/Erk 1/2的磷酸化后,检测PTTG1的表达情况。结果显示,HCV转染的细胞与未转染细胞比较,PTTG1的mRNA和蛋白表达均显著增加,p-Erk1/2蛋白显著升高(P＜0.05);抑制HCV感染显著降低PTTG1的表达和MAPK/Erk1/2的磷酸化(P＜0.05);MAPK/Erk1/2抑制剂显著降低了PTTG1基因和蛋白的表达(P＜0.05)。体外HCV感染可以导致MAPK/Erk信号通路的磷酸化,进一步导致原癌基因PTTG1的表达增加,这可能是慢性HCV感染导致HCV相关性肝细胞癌发生的分子机制之一。     

原发性肝癌患者射频消融后外周血CD4+CD25+Foxp3+Treg细胞对预后的影响

目的研究射频消融术治疗原发性肝癌患者外周血CD4+CD25+Foxp3+调节性T细水平与预后的关系.方法回顾性分析102例原发性肝癌患者经射频消融治疗后外周血CD4+CD25+Foxp3+/CD4+比值与生存时间的关联.结果原发性肝癌患者射频术后CD4+CD25+Foxp3+细胞占CD4+T的比例显著降低,与临床分期、肿瘤大小、AFP水平相关.CD4+CD25+Foxp3+调节性T细胞数目与生存率相关.结论原发性肝癌患者射频消融治疗后外周血Treg水平是判断预后的独立预测指标.     

手性四薄荷基亚甲基双膦酸酯的制备与性质表征

膦酸及其酯的衍生物是有机磷化合物中重要的一部分,已被广泛应用于医药、农药、表面活性剂、金属防腐剂、高分子材料、工业软水剂等化工领域.其所含有的P—C—P键和烷氧基有许多可能的结构变化,是个很好的合成子.用亚甲基双膦酰二氯和薄荷醇反应,合成了手性四薄荷基亚甲基双膦酸酯(L2),并对其进行了IR、EA、1HNMR、31P NMR和CD等性质表征.用该双膦酸酯合成了三种新的配合物,并进行了红外表征.