FOXP3基因与支气管哮喘

调节性T细胞(Tregs)特征性表达FOXP3,FOXP3与Tregs发育和功能密切相关。近年来发现Tregs功能异常在哮喘发病过程中具有重要作用,诱导FOXP3表达是糖皮质激素和特异性免疫治疗缓解哮喘作用机制之一。FOXP3是哮喘的发病机制和治疗研究中的又一个潜在热点。     

寄生虫14-3-3基因工程疫苗研究进展

寄生虫病是危害人和动物的重要传染病之一,疫苗是目前控制寄生虫病最为经济有效的方式。近年来,免疫学及生物工程的迅速发展极大的促进了寄生虫基因工程疫苗的研究。14-3-3蛋白是一种广泛存在于真核生物中的高度保守蛋白,已被国内外学者运用于多种寄生虫基因工程疫苗的研究。本文则对国内外寄生虫14-3-3基因工程疫苗的研究进展做一综述。     

RUNX3基因与胰腺癌的关系

人类RUNT相关转录因子3(RUNX3)基因是新近发现的一种肿瘤抑制基因,其失活的主要机制是高甲基化和杂合性缺失。RUNX3基因可能是转化生长因子-β(TGF-β)转导通路中的一处重要环节,参与TGF-β上皮细胞生长的负调控作用。在胰腺癌中发现RUNX3基因表达下调,可能是胰腺癌发生过程中的关键性基因。此文对RUNX3基因的结构、功能及其与胰腺癌之间的关系作一综述。     

Runx3基因与胃癌的关系

哺乳动物Runt domain家族包括Runx1、Runx2和Runx3三个基因,均与人类疾病的发生密切相关。其中Runx3基因被认为是一个新的抑癌基因,在胃黏膜上皮细胞调控中发挥重要作用。研究发现在人类胃癌细胞系和胃癌组织中普遍存在Runx3基因表达的缺失或下调,45%～60%的胃癌细胞由于甲基化及杂合缺失而出现Runx3基因表达的缺失或下调。此文对Runx3基因的序列结构、功能及其在胃癌发生进展过程中的作用机制等方面的研究现状作一综述。     

FABP3基因对心肌细胞凋亡的影响

目的脂肪酸结合蛋白(FABP)3基因对心肌细胞凋亡的影响及机制。方法将H9C2心肌细胞分为空白对照组、阴性对照组、FABP3沉默组、FABP3沉默+空质粒组及FABP3沉默+过表达人FABP3组,转染72 h后Western印迹检测各组细胞中FABP3的蛋白表达;流式细胞仪检测细胞凋亡;Western印迹检测Cleaved caspase3、Bcl-2蛋白表达。结果空白对照组与阴性对照组及FABP3沉默组和FABP3沉默+空质粒组之间FABP3蛋白表达差异无统计学意义(P>0.05),FABP3沉默组和FABP3沉默+空质粒组FABP3的蛋白表达显著低于空白对照组与阴性对照组,FABP3沉默+过表达人FABP3组FABP3的蛋白表达显著高于FABP3沉默组和FABP3沉默+空质粒组(P<0.01);FABP3沉默组和FABP3沉默+空质粒组细胞凋亡率及Cleaved caspase3蛋白表达显著高于空白对照组与阴性对照组,Bcl-2蛋白表达显著低于空白对照组与阴性对照组FABP3(P<0.01);沉默+过表达人FABP3组细胞凋亡率及Cleaved caspase3蛋白表达显著低于FABP3沉默组和FABP3沉默+空质粒组,Bcl-2蛋白表达显著高于FABP3沉默组和FABP3沉默+空质粒组(P<0.01)。结论沉默FABP3的表达可促进H9C2心肌细胞凋亡,过表达则抑制细胞凋亡,其机制与调节Cleaved caspase3及Bcl-2蛋白表达有关。     

胃癌Runx3基因的甲基化

目的:探讨Runx3基因甲基化与胃癌的关系方法:采用MSP法检测38例配对胃癌组织、癌旁正常组织和转移淋巴结中Runx3基因甲基化的情况.结果:73.7%的胃癌组织中存在Runx3基因异常甲基化,而相应的癌旁正常组织和转移淋巴结中该基因的甲基化率分别为21.1%和65.8%.癌组织和转移淋巴结中Runx3基因甲基化的发生率显著高于癌旁正常组织(P<0.05).胃癌组织中,该基因甲基化与肿瘤大小显著相关(P =0.021),但与肿瘤大体类型、分化程度、浸润深度及生长方式等临床病理特征无关.结论:Runx3基因异常甲基化是胃癌发生、发展过程中的频繁事件,通过检测胃黏膜组织及淋巴结中该基因的甲基化情况,可能会对胃癌的早期诊断及判断淋巴结的微转移提供一定的参考价值.     

NSCLC外周血Runx3基因启动子甲基化临床意义

目的研究非小细胞肺癌(None-small cell lung cancer,NSCLC)患者外周血Runx3基因启动子甲基化的临床意义。方法选择NSCLC患者(NSCLC组)和正常健康人(CON组)为研究对象,检测并比较两组研究对象外周血Runx3基因启动子甲基化,比较外周血Runx3基因启动子甲基化与未甲基化患者R0切除率、3年生存率及总生存时间的差异。结果 NSCLC组患者外周血Runx3基因启动子甲基化率显著高于CON组(P0.05)。NSCLC组患者外周血Runx3基因启动子甲基化在胸腔积液、分化程度、肿瘤直径、淋巴结转移、远处转移和TNM分期存在明显差异(均P0.05)。NSCLC组患者Runx3基因启动子甲基化者R0切除率、3年生存率及总生存时间均显著低于未甲基化者(均P0.05)。结论 NSCLC患者外周血Runx3基因启动子甲基化异常,在病情及预后评估中具有一定临床价值。     

新基因XTP3反式激活基因TPA的克隆化研究

目的:应用抑制性消减杂交(SSH)技术构建乙型肝炎病毒(HBV)X蛋白(HBxAg)反式激活基因XTP3的差异表达的cDNA消减文库,克隆XTP3反式激活相关基因.方法:依据我室构建的HBVX蛋白反式激活基因XTP3差异表达的cDNA消减文库,利用生物信息学技术获得新基因XTP3TPA的编码序列,对其可能的氨基酸序列进行分析比较,并对其进行克隆化研究.结果:发现了HBV XTP3反式激活作用的新的靶基因,命名为XTP3TPA.结论:这一发现为阐明HBVXTP3蛋白的反式激活作用及其机制开辟了新的研究方向.     

多房棘球绦虫Em14-3-3抗原编码基因研究进展

本文介绍了多房棘球绦虫Em14-3-3蛋白，并对Em14-3-3抗原编码基因的研究进展进行了综述。     

上消化道癌肿中runx3基因甲基化研究

runx3是胃癌中新发现的抑癌基因。国外至少40％的胃癌组织中检测到runx3基因启动子区高甲基化，此种高甲基化状态直接导致基因静默，表达缺失。runx3启动子甲基化具有很高的肿瘤特异性，有望成为胃癌诊断的早期标记。鉴于runx3启动子甲基化与前肠来源组织肿瘤密切相关，我们研究runx3在我国食管鳞癌、贲门癌和胃癌中的甲基化状态及相应mRNA表达水平，探索其在这些肿瘤发生中的作用。     

Tumourigenicity of MTG8, a leukaemia-related gene, in concert with v-Ha-ras gene in BALB/3T3 cells

The MTG8 ( ETO ) gene has been identified as the translocation partner of AML1 ( PEBP2αB or CBFα2 ) gene in the AML1 / MTG8 ( ETO ) fused gene caused by t(8;21) translocation in human acute myeloid leukaemia, M2 type. Although AML1/MTG8 chimaeric protein is known to inhibit the functioning of AML1 protein, the precise function of MTG8 gene itself is not known yet. We studied the significance of MTG8 gene in the oncogenicity of AML1 / MTG8 fused gene, by introducing full-length MTG8 cDNA into both BALB/3T3 cells containing v-Ha- ras gene (Bhas 42 cells) and BALB/3T3 cells without v-Ha- ras gene.
Irrespective of the overexpression of MTG8 gene in both groups of cells, Bhas- MTG8 clones which contained v-Ha- ras gene and expressed the MTG8 gene at a level more than twice that of parental Bhas 42 cells induced cell transformation, whereas BALB- MTG8 clones without v-Ha- ras gene did not. Furthermore, injection of the transformed Bhas- MTG8 clones into the subcutaneous tissue of nude mice induced tumours, whereas that of BALB- MTG8 clones did not. These results suggest that MTG8 gene product, in cooperation with viral Ras protein, resulted in tumour formation. We provide the first evidence that MTG8 gene by itself has a carcinogenic property within the AML1 / MTG8 ( ETO ) fused gene.     

Gene frequencies of the human platelet antigen-3 in different populations.

Human platelet antigen (HPA) systems consist of more than 12 biallelic antigen polymorphisms in which a base pair substitution leads to change in an amino acid of a glycoprotein expressed on the platelet. HPA-3 is a HPA that is mentioned for possible induction of neonatal alloimmune thrombocytopenia, posttransfusion purpura, and platelet refractoriness. A summary is presented of previous reports on the gene frequencies of HPA-3 among different populations. The frequency of HPA-3a and -3b ranges from 0.50 to 0.61 and 0.38 to 0.50, respectively. A significant correlation between the population ethnicity and the gene frequencies was detected in this study. However, it is quite difficult to use HPA-3 gene as a gene marker to determine the similarity of gene population in different populations. In addition, the comparison of the heterogenicity of HPA-3 frequencies to another well-known HPA gene, HPA-1 gene demonstrates that there is a greater variation in HPA-3 frequencies than in the HPA-1 gene. There was no significant correlation between the incidence of autoimmune thrombocytopenia disorder and the HPA-3 gene polymorphism pattern.     

An interphase fluorescence in situ hybridisation assay for the detection of 3q26.2/EVI1 rearrangements in myeloid malignancies

Chromosome rearrangements involving band 3q26.2 are associated with myeloid malignancies, aberrant expression of the human ecotropic virus integration site-1 (EVI1) gene, an unfavourable prognosis and an aggressive clinical course. The 3q26.2 rearrangements are characteristically heterogeneous and typically difficult to detect in poor quality metaphases. To develop a dual-colour fluorescence in situ hybridisation (FISH) assay for the detection of 3q26.2/EVI1 aberrations, a series of 10 BAC clones corresponding to the EVI1 gene region were systematically evaluated and narrowed down to two probe sets; one probe set encompassed the EVI1 gene extending centromeric, while the second probe set covered the EVI1 gene and extends telomeric. Both probe sets were evaluated on 35 patient samples with cytogenetically defined 3q26.2 rearrangements collected at various treatment time points, the inv(3)(q21q26.2) Kasumi-4 cell line, and 10 known negative samples. The two-probe set strategy identified all samples, despite the vast breakpoint heterogeneity observed. In samples from acute myeloid leukaemia and myelodysplastic syndrome cases, the majority of inversion breakpoints were 3' to EVI1 whereas 3q26.2 translocation breakpoints frequently mapped 5' to EVI1. However, two 3q26.2 translocation samples had breakpoints 3' to EVI1. Most inv(3q) chronic myeloid leukaemia samples showed breakpoints within the EVI1 gene. This study demonstrated that, despite the extensive breakpoint heterogeneity observed with 3q26.2 aberrations, this FISH strategy is effective for the detection of 3q26.2 abnormalities in myeloid malignancies.     

Inadequate lung development and bronchial hyperplasia in mice with a targeted deletion in the Dutt1/Robo1 gene.

Chromosome 3 allele loss in preinvasive bronchial abnormalities and carcinogen-exposed, histologically normal bronchial epithelium indicates that it is an early, possibly the first, somatic genetic change in lung tumor development. Candidate tumor suppressor genes have been isolated from within distinct 3p regions implicated by heterozygous and homozygous allele loss. We have proposed that DUTT1, nested within homozygously deleted regions at 3p12-13, is the tumor suppressor gene that deletion-mapping and tumor suppression assays indicate is located in proximal 3p. The same gene, ROBO1 (accession number ), was independently isolated as the human homologue of the Drosophila gene, Roundabout. The gene, coding for a receptor with a domain structure of the neural-cell adhesion molecule family, is widely expressed and has been implicated in the guidance and migration of axons, myoblasts, and leukocytes in vertebrates. A deleted form of the gene, which mimics a naturally occurring, tumor-associated human homozygous deletion of exon 2 of DUTT1/ROBO1, was introduced into the mouse germ line. Mice homozygous for this targeted mutation, which eliminates the first Ig domain of Dutt1/Robo1, frequently die at birth of respiratory failure because of delayed lung maturation. Lungs from these mice have reduced air spaces and increased mesenchyme, features that are present some days before birth. Survivors acquire extensive bronchial epithelial abnormalities including hyperplasia, providing evidence of a functional relationship between a 3p gene and the development of bronchial abnormalities associated with early lung cancer.     

一个2型糖尿病家系ATP敏感性钾通道基因突变分析

目的了解ATP敏感性钾通道（KATP）基因突变在一个2型糖尿病（T2DM）家系中的发生情况。方法提取家系成员的外周血DNA，用PCR扩增磺酰脲类受体1（SUR-1）基因第16、18、31外显子和KIR 6.2基因，用单链构象多态性分析（SSCP）检测PCR产物，对SSCP电泳结果异常者进行DNA序列分析。结果（1）在17名家系成员中，未检测到SUR-1基因第18号外显子ACC→ACT和第31外显子AGG→AGA突变；（2）SUR-1基因第16号外显子-3C→T的T等位基因频率为65％，比普通T2DM人群高8％；（3）KIR 6.2基因E23K的K等位基因频率38％，比普通T2DM人群低3％。结论SUR-1基因第16号外显子-3C→T多态性可能与饮食、环境等因素共同作用，参与该家系T2DM的发生和发展。     

Two developmental genes encoding sigma factor homologs are arranged in tandem in Bacillus subtilis.

The sporulation-essential gene spoIIG of the Gram-positive bacterium Bacillus subtilis encodes the sporulation-specific sigma factor sigma 29(sigma E). We report here the initial characterization of a gene, referred to as ORF3, located immediately downstream of the spoIIG gene. The results indicate that ORF3 encodes a sigma homolog, whose expression is highly regulated during development. Analysis of the ORF3 nucleotide sequence reveals an open reading frame encoding a polypeptide of 260 amino acid residues (molecular mass of 30.1 kDa). Its predicted amino acid sequence shows significant similarity to that of other RNA polymerase sigma factor sequences. S1 nuclease mapping experiments indicate that ORF3 is initially cotranscribed with spoIIG from about 1 to 4 hr into the sporulation process and that later on ORF3 is transcribed independently from a new site located between spoIIG and ORF3. The role of ORF3 was investigated by constructing a deletion mutation in its structural gene. The mutant exhibits normal growth but is unable to produce heat-resistant spores. We propose that the ORF3 gene product is a sigma factor or a related peptide essential for sporulation at a late stage of development.     

炎症性肠病患者抑制性杀伤细胞免疫球蛋白样受体基因多态性分析

目的 分析炎症性肠病(inflammatory bowel disease,IBD)患者抑制性杀伤细胞免疫球蛋白样受体(killer cell immunoglobulin-like receptor,iKIR)基因多态性,探讨iKIR基因多态性与IBD的关联性.方法 收集100例溃疡性结肠炎(UC)、52例克罗恩病(CD)患者和106名种族匹配的健康对照者外周血DNA标本,采用序列特异性引物聚合酶链反应(PCR-SSP)方法,分析上述对象iKIR基因位点的多态性,计算iKIR基因表型频率和基因频率,比较IBD患者与健康对照者间的差异.结果 iKIR基因(包括KIR2DL1、KIR2DL2、KIR2DL3、KIR2DL4、KIR2DL5、KIR3DL1、KIR3DL2、KIR3DL3)在IBD患者和健康对照组均有不同程度的表达.UC患者KIR2DL1和KIR2DL3表现型频率比健康对照组显著降低(P=0.001),而KIR2DL2、KIR2DL4、KIR2DL5、KIR3DL1、KIR3DL2和KIR3DL3表现型频率与健康对照组比较差异无统计学意义(P＞0.05).CD患者KIR2DL1表现型频率比健康对照组显著降低(P=0.007),而其余iKIR基因表现型频率与健康对照组比较差异无统计学意义(P＞0.05).结论 KIR2DL1和KIR2DL3表现型频率在UC患者中显著下降,提示其与UC的易感性有密切关系; 而KIR2DL1基因可能与CD易感性密切相关.