HLA-DR、DQ等位基因与精神分裂症相关性的研究

目的 证明HLA-DR、DQ等位基因与精神分裂症的发病密切相关。方法 HLA-DR、DQ等位基因检测：PCR-SSP分型。结果 发现在大连地区随机选择的精神分裂症患者的HLA-DQ8基因的频率(9．0％)明显高于正常对照(2．5％)。精神分裂症患者的HLA-DR、DQ等位基因的某些位点与免疫指标的改变有相关性。结论 ①HLA-DQ8基因与精神分裂症有关联，可以认为HLA-DQ8基因可能是精神分裂症的易感基因。②HLA-DR、DQ等位基因的某些组合可能是精神分裂症发病的危险组合模式，对预测精神分裂症的基因易感性具有潜在的应用价值。③精神分裂症的免疫指标的改变与HLA-DR、DQ等位基因的某些位点有相关性，说明精神分裂症与它的免疫指标的变化可能有内在的联系。     

原发性肥厚型心肌病与HLA0DQ的相关性研究

本文用ＰＣＲ／ＳＳＯ方法对４１例原发性肥厚型心肌病患者和５２例正常人ＨＬＡ－ＤＱＡ１和ＤＱＢ１基因的多态性进行分析。发现，在肥厚型心肌病患者中，ＤＱＡ１＊０２０１，ＤＱＢ１＊０５０４，０５０２等位基因频率明显较低，其相对风险值分别为９．５１、５．８７和１１．６０；而ＤＱＡ１＊０５０１，ＤＱＢ１＊０３０３１的频率明显地高，相对风险值分别为２．９３和６．６５。初步认为，原发性肥厚型心肌病与某些ＨＬＡ－     

LncRNA DQ786243促进肝细胞癌增殖及机制分析

目的探讨长链非编码RNA DQ786243(LncRNA DQ786243)促进肝细胞癌细胞增殖的作用机制。方法采用qRT-PCR法检测175例肝细胞癌癌组织及对应癌旁正常组织中LncRNA DQ786243的表达;在Hep G2细胞中瞬时转染LncRNA DQ786243的小干扰RNA片段(si-DQ786243),CCK-8实验检测降低LncRNA DQ786243的表达对细胞增殖能力的影响,Western blot法检测降低LncRNA DQ786243表达对p18蛋白表达的影响;在Hep G2细胞中瞬时共转染si-DQ786243、p18的小干扰RNA片段(si-p18),CCK-8法检测同时降低LncRNA DQ786243、p18的表达对细胞增殖能力的影响。结果肝细胞癌组织中LncRNA DQ786243的表达增加(P 0.05);在Hep G2细胞中降低LncRNA DQ786243的表达,细胞增殖减慢,p18表达增加(P均0.05);降低p18表达可部分逆转LncRNA DQ786243表达下降导致的细胞增殖能力下降(P 0.05)。结论 LncRNA DQ786243可通过下调p18的表达促进肝细胞癌细胞的增殖,进而促进肝细胞癌的发生、发展。     

西双版纳傣族及上海汉族群体HLA－DR2相关的DR／DQ单倍型分析

对４４名西双版纳傣族和９名上海地区汉族ＤＫ２阳性个体进行了与其相关的ＤＲ／ＤＱ单倍型组合的分析。傣族群体中ＤＲＢＩ－ＤＲ２亚型分布以＊１６０２与＊１５０２为最常见，其等位基因频率分别为４３．６％与，４０．０％和汉族群体中以＊１５０１为主明显不同。傣族群体中共检出１０种与ＤＲ２相关联的ＤＲ／ＤＱ单倍型；最常见的是ＤＲＢ１＊１６０２、ＤＲＢ５＊０１０１、ＤＱＡ１＊０１０２、ＤＱＢ１＊０５０２（３４．５％）与汉族及其他群体明显不同，本研究表明傣族不仅具有高频率的ＤＲ２，而且与ＤＲ２相关联的ＤＲＢ１、ＤＲＢ５、ＤＱＡ１、ＤＱＢ１单倍型组合有其独特性。     

β2-Agonists and exercise-induced asthma

β₂-Agonists taken immediately before exercise provide significant protection against exercise-induced asthma (EIA) in most patients. However, when they are taken daily, there are some negative aspects regarding severity, control, and recovery from EIA. First, there is a significant minority (15–20%) of asthmatics whose EIA is not prevented by β₂-agonists, even when inhaled corticosteroids are used concomitantly. Second, with daily use, there is a decline in duration of the protective effect of long-acting β₂-agonists. Third, if breakthrough EIA occurs, recovery of lung function is slower in response to a β₂-agonist, and additional doses are often required to achieve pre-exercise values. If a person who takes a β₂-agonist daily experiences problems with exercise, then the physician should consider changing the treatment regimen to achieve better control of EIA. These problems likely result from desensitization of the β₂-receptor on the mast cell, which enhances mediator release, and on the bronchial smooth muscle, which enhances the bronchoconstrictor response and delays recovery from EIA. These effects are reversed within 72 h after cessation of a β₂-agonists. The important clinical question is: Are we acutally compromising the beneficial effects of β₂-agonists on the prevention and recovery from EIA by prescribing them daily? Patients with EIA need to ensure that their doses of inhaled corticosteroid or other anti-inflammatory therapy are optimized so that, if necessary, a β₂-agonist can be used intermittently as prophylactic medication with greater confidence in the outcome.     

云南白族系统性红斑狼疮与HLA-DR、DQ相关性的研究

系统性红斑狼疮（ｓｙｓｔｅｍｉｃｌｕｐｕｓｅｒｙ－ｔｈｅｍａｔｏｓｕｓ,ＳＬＥ）的发病机理极为复杂。近年来研究表明,遗传因素在ＳＬＥ的发病中起决定性的作用。ＨＬＡ是迄今发现的最具多态性的遗传系统,它具有地区、种族、民族等的差异,其中ＨＬＡ－ＤＱ、ＤＲ等位基因的多态性与ＳＬＥ易感性是近几年研究的热点。我们运用单克隆抗体微量淋巴毒试验（ｍｏｎｏｃｌｏｎａｌａｎｔｉｂｏｄｉｅｓｍｉｃｒｏｃｙ－ｔｏｔｏｘｉｃｉｔｙａｓｓａｙ）［１］,探讨云南白族ＳＬＥ与ＨＬＡ－ＤＲ、ＤＱ的相关性。为进一步探讨ＳＬＥ免疫…     

BML-111对PM2.5诱导外周血Th1/Th2及ILC2失调的影响

本文主要探究PM2.5对小鼠外周血Th1/Th2及ILC2水平的影响以及BML-111的作用。通过分离培养小鼠PBMC,采用不同剂量PM2.5处理细胞,检测细胞增殖活性,筛选PM2.5适宜剂量。同时将细胞随机分为NC组、PM2.5组、BML-111组和拮抗剂Boc-2组,分别使用0 μg/mL PM2.5、50 μg/mL PM2.5、10 μmol/L BML-111和10 μmol/L Boc-2处理细胞,检测炎性因子的含量、Th1和Th2以及ILC2百分比、T-bet和GATA3的mRNA表达。结果发现,不同剂量PM2.5均能抑制PBMC的增殖率;PM2.5能够促使PBMC释放炎性因子,增加T-bet和GATA3的mRNA表达,诱导Th2分化,导致Th1/Th2失衡,同时提高ILC2水平。BML-111可降低炎性因子水平,抑制T-bet和GATA3的mRNA表达,降低免疫细胞水平,恢复Th1/Th2平衡,但拮抗剂Boc-2能部分逆转BML-111的作用。因此,脂氧素受体激动剂BML-111能够对PM2.5诱导的免疫炎性反应发挥有效抑制作用,这一作用可能是通过降低炎性因子的表达和ILC2百分比并维持免疫细胞Th1/Th2平衡来实现的。     

HLA DR/DQ alleles and risk of type I diabetes in childhood: a population–based case–control study

Abstract The objective was to evaluate HLA DR/DQ alleles and their risk factor for type 1 diabetes in the Abruzzo region (central Italy). Sixty incident cases from the Abruzzo region were studied together with 120 unrelated control subjects living in the same administrative areas. The relative risk of diabetes associated with the alleles under study was calculated by deriving the odds ratio (OR) maximum likelihood estimates and their 95% confidence intervals (CI) by the exponentiation of the logistic regression beta–parameter. The combination DRB1*03/DQA1*0501/DQB1*0201 was found in 20.0% of patients and 7.1% of the control subjects, conferring an OR of 4.04 and a CI of 1.97–8.49. The combination DRB1*04/DQA1*0301/DQB1*0302 was found in 23.3% of diabetic patients and 6.7% of controls, giving an OR of 5.69 and a CI of 2.77–12.05. DRB1*11/DQA1*0505/DQB1*0301 and DQA1*0505/DQB1*0301 were negatively associated with type 1 diabetes (OR=0.27, CI 0.11–0.57; OR=0.07, CI 0.02–0.19). The DQA1 genotype at risk was found to be DQA1*0301/DQA1*0501: OR=23.80, CI 2.97–190.89, as it occurred with the highest frequency in the patient group. The DQB1 genotype at risk was found to be DQB1*0201/DQB1*0302, which occurred in 13.3% of patients but in only 1.1% of the control group (OR=29.75, CI 5.36–549.25). Our results shed further light on the risk of development of this disease during a specific time period in an area where the overall incidence of type 1 diabetes is known.     

PM2.5通过HDAC2介导VEGF低表达致小鼠宫内生长受限

目的探讨孕期PM2.5暴露致小鼠宫内生长受限(IUGR)的组蛋白修饰机制。方法给予孕期小鼠持续PM2.5暴露,对照组予以0.9%氯化钠溶液水暴露,空白对照组不予任何处理;检测出生体质量;利用定量PCR和Western blot检测组蛋白去乙酰化酶1/2/3(HDAC1/2/3)、血管内皮生长因子(VEGF)表达;荧光测定法检测HDAC1、HDAC2及HDAC3活性;ChIP-PCR技术检测HDAC1/2与VEGF启动子结合水平。结果与对照组相比,PM2.5暴露组小鼠出生体质量显著降低(P0.05);PM2.5暴露组胎盘中HDAC1,HDAC2在mRNA及蛋白水平表达显著升高(P0.05),VEGF表达明显下降(P0.05);与对照组相比,PM2.5暴露组小鼠胎盘中HDAC2酶活性显著升高(P0.05);ChIP-PCR发现,与对照组相比,HDAC2与VEGF启动子结合水平显著升高(P0.05)。结论孕期PM2.5暴露模型中,HDAC2介导胎盘VEGF低表达可能引起胎盘血供不足,进而引起胎鼠宫内生长受限。     

新疆维族人群HLA—DR—DQ单倍型研究

为了解ＨＬＡ第２类基因（ＨＬＡ－ＤＲ－ＤＱ，－ＤＰ位点）在中国人群中的分布情况，应用ＰＣＲ／ＳＳＯ方法对新疆的主要民族维吾尔族人９２例进行了ＨＬＡ－ＤＲＢ１、ＤＲＢ３、ＤＲＢ５和ＤＱＡ１、ＤＱＢ１五位点等位基因进行了分析，计算了它们在该人群中的分布频率，推导了ＤＲ－ＤＱ五位点单倍型的结构及分布。通过与世界各主要人种和中国北方汉族的比较，证明维族在中华民族有共同基因背景的基础上，还表现出与西方人种有一定程度的血缘交流。为研究古丝绸之路人口迁移对中国维族遗传特征的影响提供了资料。     

Presence of β2-Microglobulin on B- and T-Cells and Lymphocytotoxicity of Anti-β2-Microglobulin Sera

Isolated normal lymphocytes and those of patients with chronic lymphocytic leukemia were shown by immunofluorescence to bear β₂-microglobulin in or on their membranes. Isolated thymocytes displayed similar membrane-associated fluorescence. These findings indicate that both B- and T—cells carry B₂-microglobulin in or on their membranes. Antisera against β₂-microglobulin were found to be cytotoxic in the presence of complement to normal and tissue culture lymphocytes. The presence of β₂-microglobulin found on cells other than B- and T-lymphocytes and the possible function(s) of β₂-microglobulin is discussed.     

DRβ1*1501, DQβ1*0602 donor allelic haplotype and humoral antibody episodes of acute renal allograft rejection

The present investigation was designed to show the effect of molecular HLA class II DR and DQ allelic differences between donor and recipient on humoral antibody rejection identified by C4d peritubular capillary staining. The hypothesis is that expression of the DRβ1*1501, DQβ1*0602 allele in the donor kidney increases the likelihood of humoral antibody rejection. We found that 67% (n = 18) of DR15 and/or DQ6 haplotype donor kidneys induced humoral antibody renal allograft rejection; 35% (n = 40) of DR15 and/or DQ6 haplotype donor kidneys failed to induce humoral antibody renal allograft rejection (p = 0.02). 42% (n = 31) of C4d+ recipients had donors with DR15; 17% (n = 42) of C4d recipients had donors with HLA-DR15 (p = 0.01).We compared donor haplotype alleles of 4 C4d+ with 6 C4d− recipients by high resolution molecular typing; 3 of 4 C4d+ recipients had a donor with the DRβ1*1501/DQβ1*0602 allele. This allele was absent in all C4d− donors. 35% of C4d+ recipients had 2 DR mismatches when compared to 36% of C4d− recipients. Our results, suggest that the DRβ1*1501, DQβ1*0602 allele in the donor kidney increases the risk of humoral antibody episodes of acute rejection, and signals the need for C4d staining of renal biopsies. Future analysis of additional donor and recipient haplotypes will establish whether or not this is a useful predictor of humoral rejection episodes.     

采用PCR-RFLP技术检测中国人HLA纯合细胞DQ基因多态性

本文采用PCR-RFLP方法对7株中国人HLA纯合细胞的DQA1、DQB1基因作基因分型,检出了这些细胞株的DQ基因类型,证实了中国人群存在着一种DRw12与DQA1*0601-DQB1*0301连锁的新单倍型。     

组织相容性复合体DQ异二聚体与I型糖尿病的相关性

Ｉ型糖尿病是一种多基因遗传的慢性自身免疫性疾病 ,组织相容性复合体 (ＨＬＡ)构成其遗传因素的 6 0 % ,是Ｉ型糖尿病的主效基因。研究资料表明 :ＨＬＡ Ⅱ类基因区ＤＱＡ1基因编码的ＤＱα链第 5 2位和ＤＱＢ1基因编码的ＤＱβ链第 5 7位氨基酸残基的性质是Ｉ型糖尿病易感性的决定因子 ;由于ＤＱα链和ＤＱβ链形成的异二聚体与Ｉ型糖尿病存在着易感相关性 ,而且这种相关性存在一定的人种差异。中国人无此方面的研究报道 ,因此本课题应用聚合酶链反应和斑点杂交技术对研究对象的ＨＬＡ基因进行分型并对中国人ＨＬＡ ＤＱ异二聚体与Ｉ型糖…     

β2-adrenergic receptor and UCP3 variants modulate the relationship between age and type 2 diabetes mellitus

Background  

It is widely accepted that Type 2 Diabetes Mellitus (T2DM) and other complex diseases are the product of complex interplay between genetic susceptibility and environmental causes. To cope with such a complexity, all the statistical and conceptual strategies available should be used. The working hypothesis of this study was that two well-known T2DM risk factors could have diverse effect in individuals carrying different genotypes. In particular, our effort was to investigate if a well-defined group of genes, involved in peripheral energy expenditure, could modify the impact of two environmental factors like age and obesity on the risk to develop diabetes. To achieve this aim we exploited a multianalytical approach also using dimensionality reduction strategy and conservative significance correction strategies.