CO对局灶性缺血脑组织血脑屏障通透性的影响

目的:研究一氧化碳及其限速酶(血红素氧合酶-1)对局灶性缺血脑组织血脑屏障通透性的影响。方法:将SD大鼠随机分为3组(n=6),使用血红素氧合酶诱导剂及抑制剂腹腔注射,用等量生理盐水腹腔注射作为对照组,12h后复制MCAO模型。梗塞后24h后检测血液中一氧化碳浓度、血脑屏障通透性。结果:诱导剂组一氧化碳浓度明显高于对照组(P＜0.01),血脑屏障通透性明显低于对照组(P＜0.05),而抑制剂组一氧化碳浓度明显低于对照组(P＜0.01),血脑屏障通透性明显高于对照组(P＜0.05)。血红素氧合酶诱导剂、抑制剂对非梗塞侧的血脑屏障通透性没有影响(P＞0.05)。结论:一氧化碳作为一种信使分子,脑缺血时浓度升高具有保护血脑屏障的作用。     

Association of DAAO with schizophrenia in the Chinese population

Recently, the gene called DAAO was reported to be associated with schizophrenia in the French Canadian populations. Here, we report a result obtained in the study of our large collection of 547 schizophrenia cases and 536 controls in the Chinese population. Six single-nucleotide polymorphisms (SNPs) were genotyped at and around the DAAO locus, covering a 10-kb region entirely encompassing the complementary DNA sequences of DAAO. We found statistically significant differences in allele distributions on one marker: SNP rs3741775 (P = 0.0000001). In the haplotype analysis based on the information of linkage-disequilibrium block across this gene locus, we demonstrated a highly significant association between schizophrenia and a DAAO haplotype (P = 2.0173 x 10(-21)), which therefore provides an independent statistical support for association of the DAAO gene with schizophrenia and indicates that the DAAO gene may play a significant role in the etiology of schizophrenia in the Han Chinese.     

兔急性胰腺炎并发十二指肠粘膜损伤与一氧化氮合酶改变的关系

目的:探讨急性胰腺炎并发十二指肠粘膜损伤与一氧化氮合酶(nitric oxide synthase,NOS)改变的关系。方法:用胰管结扎及加压注射法建立大白兔急性胰腺炎模型,采用黄递酶组织化学染色法观察与比较两组动物胰腺及十二指肠组中NOS的变化。结果:经Winslow法测定血清淀粉酶分析及组织学检查,急性胰腺炎模型建立;经NADPH-d染色表明:实验组NOS染色强度明显高于对照组。结论:一氧化氮(nitric cxide,NO)在急性胰腺炎并发十二指肠粘膜损伤的病变过程中起重要的介导作用。     

Linkage Disequilibrium and Haplotype Architecture for two ABC Transporter Genes (ABCC1 and ABCG2) in Chinese Population: Implications for Pharmacogenomic Association Studies

Information about linkage disequilibrium (LD) patterns and haplotype structures for candidate genes is instructive for the design and analysis of genetic association studies for complex diseases and drug response. ABCC1 and ABCG2 are genes coding for two multidrug resistance (MDR) associated transporters; they are also related to some pathophysiological traits. To pinpoint the LD profiles of these MDR genes in Chinese, we systemically screened 27 unrelated individuals for single nucleotide polymorphisms (SNPs) in the coding and regulatory regions of these genes, and thereby characterized their haplotype structures. Despite marked variations in haplotype diversity, LD pattern and intragenic recombination intensity between the two genes, both loci could be partitioned into several LD blocks, in which a modest number of haplotypes accounted for a high fraction of the sampled chromosomes. We concluded that each locus has its own genomic LD profile, but that they still share a common segmental LD architecture with low haplotype diversity. Our data will benefit genetic association studies of complex traits and drug response possibly related to these genes.     

Induction of a cytotoxic T cell response by co-injection of a T helper peptide and a cytotoxic T lymphocyte peptide in incomplete Freund's adjuvant (IFA): Further enhancement by pre-injection of IFA alone

We have previously demonstrated that it is possible to induce a consistent and strong cytolytic T lymphocyte (CTL) response to synthetic peptides, corresponding to poorly immunogenic malaria CTL epitopes, by co-injecting them with peptides representing defined T helper (Th) epitopes in incomplete Freund's adjuvant (IFA). In this study we have tested different immunization protocols to improve further the elicitation of the CTL response. We show that the CTL response to a mixture of Th + CTL peptides administered in IFA was further enhanced by a previous injection of the Th epitope peptide in IFA. Moreover, we found that the response could be significantly augmented by a pre-injection of IFA alone. This enhancement was observed only if the Th epitope was also present in the second injection. The number of lymph node cells recovered was 2–3-fold higher in mice pre-injected with IFA, but the increase in specific CTL activity, expressed as lytic units per animal, by pre-injection of IFA was at least 10–20-fold. Thus, pre-injection of IFA clearly increases the magnitude of a subsequent CTL response.     

慢性肾小球肾炎病人白细胞糖皮质激素受体的变化

以氚标记的地塞米松(~3H-Dex)为配体,用一点分析法测定了23例慢性肾小球肾炎病人混合白细胞的糖皮质激素受体(GCR),平均为8825±2429位点/细胞((?)±SD)。与正常人5154±1635位点/细胞相比相差十分显著,P<0.01。其中16例并发尿毒症患者的GCR平均为9464±2571位点/细胞((?)±SD)。对这种变化的可能机制和临床意义进行了讨论。     

纯化的结核杆菌多肽抗原刺激人γδT细胞的效应分析

目的：探讨从结核杆菌多肽抗原(Mtb-Ag)纯化的多肽(C主肽)对人新鲜外周血γδT细胞的促增殖效应以及对已活化扩增的T细胞再次刺激的激活效应。方法：采用不同剂量的C主肽体外刺激健康人外周血PBMC，培养10天时经流式细胞仪检测细胞表型；另外以γδT细胞活化标志分子CD69的表达为指标，分析C主肽对已被Mtb-Ag激活扩增13天的γδT细胞再次刺激的激活效应。同时以MTT法检测C主肽的再刺激对已活化扩增的γδT细胞的促增殖活性。结果：结核杆菌C主肽对人新鲜的γδT细胞具有显著扩增效应；当C主肽再刺激已经活化的γδT细胞时，可使其显著表达CD69分子，同时对γδT细胞具有显著促增殖活性。结论：结核杆菌C主肽可能是Mtb-Ag发挥特异性激活人γδT细胞的有效成分。     

Effects of chloride and potassium channel blockers on apoptotic cell shrinkage and apoptosis in cortical neurons

K⁺ and Cl^– homeostasis have been implicated in cell volume regulation and apoptosis. We addressed the hypothesis that K⁺ and Cl^– efflux may contribute to apoptotic cell shrinkage and apoptotic death in cultured cortical neurons. CLC-2 and CLC-3 chloride channels were detected in cultured cortical neurons. The Cl^– channel blockers 4,4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS), 4-acetamido-4-isothiocyanatostilbene-2,2-disulfonic acid (SITS) and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) inhibited the outwardly rectifying Cl^– current, prevented apoptotic cell shrinkage, and mildly attenuated cell death induced by staurosporine, C₂-ceramide, or serum deprivation. Cl^– channel blockers, however, at concentrations that prevented cell shrinkage had no significant effects on caspase activation and/or DNA fragmentation. Cell death in the presence of a Cl^– channel blocker was still sensitive to blockade by the caspase inhibitor z-Val-Ala-Asp(OMe)-fluoromethyl ketone (z-VAD-fmk). Electron microscopy revealed that, although DIDS prevented apoptotic cell shrinkage, certain apoptotic ultrastructural alterations still took place in injured neurons. On the other hand, the K⁺ channel blocker tetraethylammonium (TEA), clofilium, or the caspase inhibitor z-VAD-fmk prevented cell shrinkage as well as caspase activation and/or DNA damage, and showed stronger neuroprotection against apoptotic alterations and cell death. The results indicate that neurons may undergo apoptotic process without cell shrinkage and imply distinct roles for Cl^– and K⁺ homeostasis in regulating different apoptotic events.     

FcγRⅡB1介导的信号传导异常与SLE患者B细胞的过度活化

目的:观察系统性红斑狼疮(SLE)患者B细胞表面功能分子表达的特征及其功能状态,评价以FcγRⅡB1(CD32)为代表的B细胞自身抑制调节机制在SLE发病中的作用。方法:采用Ficoll密度梯度离心法分离出人外周血单个核细胞(PBMC),并以免疫磁珠法(MACS)分离纯化B细胞。采用荧光分光光度法检测B细胞受不同激活物刺激后细胞内钙([Ca2 ]i)的反应。用ELISA法检测B细胞与刺激物共同培养后所分泌IgG的量。采用流式细胞术及间接免疫荧光染色法,检测B细胞膜表面CD32、CD19及IgM的表达水平。结果:(1)以羊抗人μ链的F(ab′)2片段及完整IgG分别刺激SLE患者B细胞时,其[Ca2 ]i反应的比值显著低于类风湿性关节炎(RA)患者(P<0.05)及正常人对照(P<0.01)。(2)分别用葡萄球菌A蛋白(SPA)单独刺激与SPA和羊抗人μ链的完整IgG抗体共同刺激SLE患者的B细胞所分泌的IgG的比值,明显低于RA患者及正常人对照组(P<0.05)。(3)SLE患者与RA患者及正常对照组B细胞上CD19、CD32及IgM的表达无统计学意义(P>0.05)。结论:SLE患者B细胞上CD32抑制性信号传导的异常,可能是导致B细胞过度活化的重要机制。