CagA基因对胃粘膜上皮细胞增殖和凋亡的影响

目的 观察幽门螺杆菌（Ｈｐ）及其ＣａｇＡ基因对细胞增殖和凋亡的影响,进而探讨Ｈｐ增加胃癌发生危险性的机制。方法 研究对象为１１９例慢性胃炎患者,其中Ｈｐ阳性６８例,Ｈｐ阴性５１例。应用ｋｉ－６７免疫组化技术评价胃幽门窦上皮细胞增生,用切口末端标记法（ＴＵＮＥＬ）检测胃上皮细胞凋亡,应用聚合酶链反应（ＰＣＲ）技术检测Ｈｐ的ＣａｇＡ基因。结果 Ｈｐ阳性患者的增殖指数（ＬＩ）和凋亡指数（ＡＩ）显著高于Ｈ     

苗族人群幽门螺旋杆菌CagA因子与胃癌的相关性分析

目的探讨怀化地区麻阳苗族自治县苗族人群幽门螺杆菌（Hp）感染特别是其细胞色素相关基因（CagA）与胃癌的相关性。方法收集湖南怀化麻阳苗族自治县人民医院2001—2008年经病理检查确诊的胃癌患者100例,其中苗族52例,汉族48例,苗族患者平均（60．124-12．35）岁,汉族患者平均年龄（67．75±11．64）岁。分别检测两族胃癌患者Hp和HpCaA基因株的感染率。结果苗族人群胃癌组Hp的阳性率均显著高于汉族人群胃癌组（P〈0．05）,苗族人群胃癌组HpCagA基因株阳性率均显著高于汉族人群胃癌（P〈0．05）。结论HpCagA基因株感染与胃癌关系密切,苗族人群胃癌患者CagA基因株感染率显著高于汉族胃癌患者组,这是否是苗族人群胃癌发病较早、发病率较高的一种原因尚待进一步研究。     

Helicobacter pylori CagA EPIYA Motif Variations Affect Metabolic Activity in B Cells

Background: Helicobacter pylori (Hp) colonizes the human stomach and can induce gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. Clinical observations suggest a role for the Hp virulence factor cytotoxin-associated gene A (CagA) in pathogenesis. The pathogenic activity of CagA is partly regulated by tyrosine phosphorylation of C-terminal Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs in host cells. However, CagA differs considerably in EPIYA motifs, whose functions have been well characterized in epithelial cells. Since CagA is fragmented in immune cells, different CagA variants may exhibit undetected functions in B cells. Methods: B cells were infected with Hp isolates and isogenic mutants expressing different CagA EPIYA variants. CagA translocation and tyrosine phosphorylation were investigated by Western blotting. Apoptosis was analyzed by flow cytometry and metabolic activity was detected by an MTT assay. Results: Isogenic CagA EPIYA variants are equally well translocated into B cells, followed by tyrosine phosphorylation and cleavage. B cell apoptosis was induced in a CagA-independent manner. However, variants containing at least one EPIYA-C motif affected metabolic activity independently of phosphorylation or multiplication of EPIYA-C motifs. Conclusions: The diverse structure of CagA regulates B cell physiology, whereas B cell survival is independent of CagA.     

幽门螺杆菌cagA和hrgA基因与胃癌慢性胃炎相关性研究

目的探讨幽门螺杆菌（Hp）菌株中cagA和hrgA基因对胃癌、慢性萎缩性胃炎的致病作用及其检测的意义。方法胃镜下诊断慢性胃炎的病例，钳取活体组织标本，组织学检查。胃癌及消化性溃疡术后切除标本，组织学检查确认，快速尿素酶法和聚合酶链反应（PCR）检测。结果胃腺癌中18例hrgA阳性、6例hrgA阴性，20例cagA阳性、4例cagA阴性；消化性溃疡中6例hrgA阳性、8例hrgA阴性，12例cagA阳性、2例cagA阴性；慢性萎缩性胃炎中30例Hp阳性、8例Hp阴性，22例cagA阳性、16例cagA阴性；慢性浅表性胃炎中2例cagA阳性、20例cagA阴性。结论Hp感染与胃癌、慢性萎缩性胃炎的发生有密切关系。PCR检测较快速尿素酶法准确。检测cagA和hrgA基因对了解Hp菌株的致病性、估计疾病程度、了解病变预后及临床治疗都具有重要意义。     

幽门螺杆菌CagA抗体与消化系统疾病的关系研究

目的探讨贵阳地区CagA阳性幽门螺杆菌感染状况及其与消化系统疾病的关系。方法收集2007年10月至2008年4月266例于贵阳医学院附院消化科住院和消化科门诊Hp菌株感染患者．其中男144例,女122例,平均年龄（49．95士17．35）岁,用酶联免疫法检测其CagA抗体。结果266例Hp阳性患者中CagA抗体阳性189例,阳性率为71．05％。最小患者年龄8岁,最大87岁,CagA抗体阳性患者好发于30～69岁。男性患者CagA抗体阳性率为69．44％,女性患者阳性率为72．95％,男女阳性率无明显差异（P〉0．05）。在慢性胃炎（CG）、胃十二指肠溃疡（PU）、胃癌（GC）、食管炎（RE）患者中,CagA抗体的阳性率分别为67．544％、73．17％、90．00％、53．33％,差异有显著意义（P〈0．05）。结论本地区上述消化系统疾病发生的患者与CagA阳性Hp菌株感染密切相关,感染的Hp绝大多数为CagA阳性菌株。     

CagA protein of Helicobacter pylori: a hijacker of gastric epithelial cell signaling

Epidemiological study has shown strong correlation between the Helicobacter pylori (H. pylori) infection and gastric carcinogenesis. However, the mechanism by which H. pylori induces gastric carcinogenesis is not known. In this review, we focused on the product of cytotoxin-associated gene A (CagA), one of the important virulence factors of H. pylori. H. pylori injects CagA protein into the host gastric epithelial cells through its needle-like structure, type IV secretion system. Injected CagA hijacks physiological signal transduction and causes pathological cellular response such as increased cell proliferation, motility, apoptosis and morphological change through different mechanisms. H. pylori has been shown to produce reactive oxygen species (ROS) in infected gastric mucosa. Although the main source of ROS production is possibly host neutrophil, we propose novel source of ROS production in this review; CagA itself can induce ROS production in gastric epithelial cell. Excessive ROS production in gastric epithelial cells can cause DNA damage and thus might involve in gastric carcinogenesis. Understanding the molecular mechanism by which H. pylori-induced carcinogenesis is important for developing new strategies against gastric cancer.     

Systematic review and meta-analysis: importance of CagA status for successful eradication of Helicobacter pylori infection

BACKGROUND: Some, but not all studies have provided evidence that the CagA status of Helicobacter pylori strains is a predictive factor for the outcome of eradication therapy. AIM: To clarify the association between CagA status and eradication outcome. METHODS: We included studies reporting the numbers of successful and failed cases in H. pylori-eradication therapy according to the CagA status. Fourteen studies (1529 patients) were included of 325 articles identified in the search. The pooled risk ratio for H. pylori-eradication failure in CagA-negative relative to CagA-positive strains and the pooled risk difference in eradication success between the two groups were used as summary statistics. Meta-regression was used for examining the source of heterogeneity. RESULTS: The summary risk ratio for eradication failure in CagA-negative relative to CagA-positive was 2.0 (95% CI: 1.6-2.4, P < 0.001), corresponding with the summary risk difference for eradication success between the groups of 11% (95% CI: 3-19%, P = 0.011). Meta-regression analysis demonstrated that usage of polymerase chain reaction examination for CagA status and a high proportion of non-ulcer dyspepsia patients were factors for heterogeneity among studies. CONCLUSIONS: Our meta-analysis confirmed the importance of the presence of CagA as a predictor for successful eradication of H. pylori.     

幽门螺杆菌HSP60、CagA抗体水平与消化性溃疡的相关性

目的探讨幽门螺杆菌(HP)HSP60、CagA抗体检测的临床意义。方法采用HelicoStick法进行末梢血幽门螺杆菌HSP60、CagA抗体检测。结果7～18岁儿童HP抗体总阳性率为14.72%,HSP-60IgG阳性率13.88%,CagAIgG阳性率6.19%。除10～12岁组的HP抗体阳性率最低外,HP抗体阳性率随年龄增长而逐渐升高,但无统计学意义。健康儿童组、慢性胃炎组、消化性溃疡组HP抗体阳性率逐渐增高,差异有统计学意义。CagA-IgG阳性率消化性溃疡组明显高于健康儿童与慢性胃炎组,差异有统计学意义。结论CagA-IgG阳性可作为诊断消化性溃疡合并HP感染的依据。HelicoStick法检测幽门螺杆菌抗体,快速、简洁、高效。     

CagA的表达对慢性胃炎Th细胞亚群分化的影响*

目的探讨幽门螺杆菌CagA的表达对慢性胃炎患者胃黏膜Th细胞亚群分化的影响。方法80例慢性胃炎患者，ELISA法测定血清CagA抗体，根据结果将慢性胃炎患者分为CagA阳性和阴性组，均取患者胃黏膜行病理检查及PCR、Western blot检测核转录因子TBX21、GATA-3、FoxP3和Rorγt的表达水平。结果 CagA抗体阳性组和阴性组分别为52例和28例，CagA抗体阳性组炎症中、重度43例（82.7%）显著高于阴性组10例（35.7%），差异有统计学意义（χ2=17.964，P<0.05）；2组间Hp菌密度差异无统计学意义。CagA抗体阳性组TBX21、Rorγt的转录及蛋白表达水平较阴性组显著下调，而GATA-3、FoxP3的转录及蛋白表达水平较阴性组显著上调。结论慢性胃炎CagA阳性患者的胃黏膜炎症程度更重，但机体却不能有效清除Hp在胃黏膜中的定植，其原因与可能存在Th0向Th2/Treg的分化偏倚有关。     

我院住院儿童幽门螺杆菌CagA多态性的临床研究

目的研究我院住院儿童感染的幽门螺杆菌（Helicobacter pylori,HP）cagA的多态性。方法应用3对不同引物对80例HP感染的患儿胃黏膜HP菌株通过PCR技术分别扩增CagA基因不同片段,检测CagA基因阳性（CagA＋）的检出率。结果HP菌株CagA基因DNA4O4bp、349bp、298bp片段分别经3对引物扩增后,CagA＋的检出率分别为51.3%、35.0%、78.8%,三者之间差别有统计学意义（χ2=31.44,P〈0.005）。结论我院住院儿童感染的幽门螺杆菌CagA基因存在多态性。     

SH2域、SHP2 cDNA的克隆鉴定和在大肠杆菌中的表达及其与CagA的相互作用

目的 研究SH2（Sre同源体2）域和SHP2（含2个SH2域的蛋白酪氨酸磷酸酶）蛋白的基因克隆和表达。方法 根据GeneBank中SH2和SHP2的基因序列设计引物,以PCR法扩增出SH2和SHP2基因,将其插入pQBO质粒中,转化进E．coli感受态细胞中,筛选阳性克隆并研究其表达。结果 所克隆的目的基因片断经PCR法鉴定和序列分析证明正确。结论 已成功地扩增SH2和SHP2基因并克隆到pQE30载体上,转化大肠杆菌菌株有表达,并探讨其与CagA（细胞毒性关联的基因A抗原）的相互作用及导致胃细胞癌变的原因。     

Capsaicin consumption, Helicobacter pylori CagA status and IL1B-31C > T genotypes: A host and environment interaction in gastric cancer

Gastric cancer (GC) has been associated with a complex combination of genetic and environmental factors. In contrast to most countries, available information on GC mortality trends showed a gradual increase in Mexico. Our aim was to explore potential interactions among dietary (chili pepper consumption), infectious (Helicobacter pylori) and genetic factors (IL1B-31 genotypes) on GC risk. The study was performed in three areas of Mexico, with different GC mortality rates. We included 158 GC patients and 317 clinical controls. Consumption of capsaicin (Cap), the pungent active substance of chili peppers, was estimated by food frequency questionnaire. H. pylori CagA status was assessed by ELISA, and IL1B-31 genotypes were determined by TaqMan assays and Pyrosequencing in DNA samples. Multivariate unconditional logistic regression was used to estimate potential interactions. Moderate to high Cap consumption synergistically increased GC risk in genetically susceptible individuals (IL1B-31C allele carriers) infected with the more virulent H. pylori (CagA+) strains. The combined presence of these factors might explain the absence of a decreasing trend for GC in Mexico. However, further research on gene–environment interactions is required to fully understand the factors determining GC patterns in susceptible populations, with the aim of recommending preventive measures for high risk individuals.     

Degraded and undegraded carrageenans and experimental gastric and duodenal ulceration

The prevention of histamine-induced gastric and duodenal ulceration in the guinea-pig has been examined using a series of undegraded and degraded carrageenans. Undegraded carrageenans were active at lower doses than degraded carrageenans. The high viscosity of the undegraded carrageenans in solution prevented their use in larger doses. Degradation of carrageenan without serious loss of sulphate, gives a product which allows the dose to be increased to an extent that its effect more than offsets the slight loss in activity caused by the degradation. No single feature of carrageenan structure can be related to anti-ulcer activity although degradation, and hence reduction of molecular size, generally reduces activity. Sulphate contents over 30% have little apparent effect on activity; κ-carrageenans were not consistently different in anti-ulcer activity from Λ-carrageenans. This contrasts with the antipeptic activity of carrageenans where κ-carrageenans are less active than their Λ-counter-parts. As with antipeptic activity, the degree of anti-ulcer activity is probably determined by a combination of structural features which includes molecular size and polyanionic properties.