Laboratory stress in normotensives,borderline hypertensives and essential hypertensives is associated with priming of phagocytic cells

The present study was designed to investigate the effect of standardized laboratory physical and mental stress on phagocytic generation of reactive oxygen species (ROS) and hormonal responses in normotensives (NT), borderline hypertensives (BH) and essential hypertensives (EH). BH were characterized by increased neurohormonal activation in the prestress situation as indicated by significant higher noradrenaline and ACTH values. Although physical stress resulted in a marked activation of the sympatho-adrenal system in all groups, the BH group revealed a strong tendency of more pronounced sympatho-adrenal response. The intracellular and extracellular production of ROS was quantified using chemiluminescence (CL) assays. Phagocytic cells of NT, BH and EH responded to stress with a significantly enhanced zymosan-stimulated luminol- and lucigenin-amplified CL, predominantly localized intracellularly. In the BH group, but not in NT and EH, significant stress-related increases of extracellularly and intracellularly generated oxidative metabolites of isolated granulocytes after stimulation with the chemotactic peptide FMLP were found. Baseline values of all measured CL parameters did not differ between NT, BH and EH. The results show that stress is followed by priming of phagocytes for enhanced oxygen radical generation. In addition to stress-related activation of intracellular ROS production granulocytes of BH showed enhanced release of oxygen metabolites into the extracellular space.     

上海汉族人群MICA基因第5外显子微卫星多态性研究

目的 了解上海地区汉族人群ＭＩＣＡ基因第５外显子微卫生多态性分布,以及ＭＩＣＡ基因与其紧密连锁的ＨＬＡ－Ｂ基因位点的关系。方法 用ＰＣＲ－异源双链分析法,对１７５名正常无关个体的ＭＩＣＡ基因第５外显子微卫星多态性的分布进行研究。结果 （１）上海地区汉族人群ＭＩＣＡ基因第５外显子存在５种等位基因,其中ＭＩＣＡ＊Ａ５最为常见（３９．１４％）,其次为＊Ａ５．１（２２．２９％）;（２）ＭＩＣＡ等位基因与Ｈ     

柯萨奇腺病毒受体在病毒性扩张型心肌病外周血白细胞中的表达及意义

目的观察柯萨奇腺病毒受体(CAR)在病毒性扩张型心肌病(DCM)外周血白细胞中的表达及意义.方法选择柯萨奇B组病毒性DCM及正常人各15例作为研究对象,采用流式细胞术检测外周血白细胞中CAR表达水平,并对DCM患者CAR表达值与心功能值[射血分数(EF)]的变化进行相关性分析.结果流式细胞术检测表明,心肌病组平均荧光强度(MFI)和阳性细胞百分率(PPC)均明显高于正常对照组,两者比较,差异均有统计学意义(t=9.39和7.21,P均<0.01),而且其MFI与EF值呈显著负相关(r=-0.64,P<0.05).结论柯萨奇B组病毒性DCM患者外周血白细胞中CAR表达水平增加,外周血白细胞CAR水平的检测,有助于DCM的诊断、判断病情和预后.     

严重腹腔感染机体免疫失衡与中医虚实证型关系的研究

目的 研究严重腹腔感染所致多脏器功能障碍综合征（MODS）患者的免疫失衡特点与中医虚实证型的相关性。方法 连续观察46例严重腹腔感染所致MODS, 采用中西医结合方法,针对病因及辨证治疗, 于入选后第1、3、7天测定外周血白细胞介素6/白细胞介素10比值（IL- 6/IL-10）、人类白细胞抗原DR位点(HLA-DR)、T辅助淋巴细胞1/2（Th1/Th2比值）、调节性T淋巴细胞（Treg）水平, 同时观察实证、虚实夹杂证、虚证等中医证型的分布规律。结果 IL-6/IL-10比值在实证与虚实夹杂证各时间点比较, 差异无统计学意义;虚证第7天较第1天下降, 同期比较, 实证、虚实夹杂证、虚证IL-6/IL-10比值依次降低。 HLA-DR水平在实证、虚实夹杂证、虚证依次降低, 实证及虚实夹杂证均未发现HLA-DR<30%的病例, 在虚证患者中, 第7天HLA-DR全部<30%,较第1天差异有统计学意义(P＜0.05)。Th1/Th2比值在实证与虚证前3天差异无统计学意义, 第7天较第1天出现下降, 虚实夹杂证1周内无变化, 同期比较, 实证、虚实夹杂证、虚证Th1/Th2比值依次降低。Treg水平在实证与虚实夹杂证前3天差异无统计学意义, 虚证第3天较第1天升高, 第3天与第7天差异无统计学意义, 同期比较, 实证、虚实夹杂证、虚证Treg水平依次升高。结论 在严重腹腔感染所致MODS病理过程中, 反映机体促/抗炎细胞因子平衡的IL-6/IL-10比值及反映免疫功能的HLA-DR、Th1/Th2比值和Treg水平均能较为准确地反映中医虚实证型, 表现为实证、虚实夹杂证、虚证时, IL-6/IL-10比值、HLA-DR和Th1/Th2依次下降, 而Treg水平依次升高。     

Complete nucleotide sequence characterization of DRB5 alleles reveals a homogeneous allele group that is distinct from other DRB genes

Next Generation Sequencing allows for testing and typing of entire genes of the HLA region. A better and comprehensive sequence assessment can be achieved by the inclusion of full gene sequences of all the common alleles at a given locus. The common alleles of DRB5 are under-characterized with the full exon-intron sequence of two alleles available. In the present study the DRB5 genes from 18 subjects alleles were cloned and sequenced; haplotype analysis showed that 17 of them had a single copy of DRB5 and one consanguineous subject was homozygous at all HLA loci. Methodological approaches including robust and efficient long-range PCR amplification, molecular cloning, nucleotide sequencing and de novo sequence assembly were combined to characterize DRB5 alleles. DRB5 sequences covering from 5′UTR to the end of intron 5 were obtained for DRB5*01:01, 01:02 and 02:02; partial coverage including a segment spanning exon 2 to exon 6 was obtained for DRB5*01:03, 01:08N and 02:03. Phylogenetic analysis of the generated sequences showed that the DRB5 alleles group together and have distinctive differences with other DRB loci. Novel intron variants of DRB5*01:01:01, 01:02 and 02:02 were identified. The newly characterized DRB5 intron variants of each DRB5 allele were found in subjects harboring distinct associations with alleles of DRB1, B and/or ethnicity. The new information provided by this study provides reference sequences for HLA typing methodologies. Extending sequence coverage may lead to identify the disease susceptibility factors of DRB5 containing haplotypes while the unexpected intron variations may shed light on understanding of the evolution of the DRB region.     

The acidic tumour microenvironment: Manipulating the immune response to elicit escape

The success of cancer treatment relies on the composition of the tumour microenvironment which is comprised of tumour cells, blood vessels, stromal cells, immune cells, and extracellular matrix components. Barriers to effective cancer treatment need to be overcome, and the acidic microenvironment of the tumour provides a key target for treatment. This review intends to provide an overview of the effects that low extracellular pH has on components of the tumour microenvironment and how they contribute to immune escape. Further, potential therapeutic targets will be discussed.     

白血病病人与健康人白细胞氧自由基及耗氧量的比较

利用电子自旋共振（ESR）自旋捕集与探针技术,观察白血病病人与健康人白细胞氧代谢过程释放活性氧自由基的种类及其耗氧量的变化。结果发现,白血病病人白细胞经豆蔻酰佛波醇乙酯（PMA）刺激只捕集到微弱的羟自由基（OH）信号,刺激前后耗氧量差别不显;健康人白细胞可得到超氧阴离子自由基（O^-2）的ESR波谱信号,耗氧量较正常呼吸即未受PMA刺激时大大增加（P＜0.001)。两组白细胞耗氧量比较,未受刺激时两无明显差别;刺激后,健康组明显高于白血病组（P＜0.001)。结论说明白血病病人白细胞缺乏呼吸爆发功能,因此耗氧量明显低于健康人白细胞。     

Serum sHLA‐G levels: A useful indicator in distinguishing colorectal cancer from benign colorectal diseases

Soluble human leukocyte antigen‐G (sHLA‐G) has been reported in malignancies and is implicated in mediating immune surveillance of tumor. The aim of our study is to detect serum sHLA‐G levels in colorectal cancer and to determine whether sHLA‐G may be helpful in distinguishing colorectal cancer from benign colorectal diseases. Serum sHLA‐G levels were determined using enzyme‐linked immunosorbent assay. Receiver operating characteristic (ROC) curve was used to evaluate the feasibility of sHLA‐G in differentiating colorectal cancer from benign colorectal diseases. Median sHLA‐G concentrations were significantly higher in colorectal cancer compared to normal colorectum, hyperplastic polyp, inflammatory bowel disease and adenoma (all at p < 0.001, respectively). ROC curve for sHLA‐G revealed an area under the curve of 84.2%, and when 88.6 U/mL was used as cutoff, a sensitivity of 72.2% and a specificity of 87.8% were achieved. Comparison of sHLA‐G and carcinoembryogenic antigen ROC curves indicated that sHLA‐G was superior to CEA in differentiating colorectal cancer from benign colorectal diseases (p < 0.001). ROC curves analysis of the combined sHLA‐G and CEA showed a higher detection capacity (area under the ROC curve, 87.4%) than that of markers considered singly. These findings reveal that serum levels of sHLA‐G are significantly increased in colorectal cancer which may serve as a potent mediator of immune escape in colorectal cancer, and sHLA‐G may be a useful indicator in differentiating colorectal cancer from benign colorectal diseases.