幽门螺杆菌感染对胃黏膜上皮细胞增殖的影响

空泡毒素 (ＶａｃＡ)是幽门螺杆菌 (Ｈｐ)的重要致病因素。根据其编码基因ｖａｃＡ信号序列的不同可分为ｓ1ａ ,ｓ1ｂ ,ｓ1ｃ和ｓ2型。ｖａｃＡｓ1ａ型菌株与胃十二指肠疾病的关系更为密切 ,可能是致胃十二指肠疾病的高毒力菌株。不同ｖａｃＡ类型的菌株对于上皮细胞增殖的影响存在差异[1] 。因此 ,我们主要观察感染ｖａｃＡｓ1ａ阳性Ｈｐ菌株 ,ｖａｃＡｓ1ａ阴性Ｈｐ菌株及Ｈｐ阴性的慢性胃炎和十二指肠球部溃疡 (ＤＵ)患者胃黏膜上皮细胞增殖情况 ,以探讨Ｈｐ及其不同菌株感染对细胞增殖的影响以及其可能的作用机制。材料与方法一、标本中…     

幽门螺杆菌vacA基因型和cagA基因及其表达产物

幽门螺杆菌（Ｈｐ）的ｖａｃＡ基因和ｃａｇＡ基因分别表达ＶａｃＡ和ＣａｇＡ蛋白两种毒力因子。两种毒力因子之间有着相互的关联，在Ｈｐ引起的胃肠疾病中具有重要作用，Ｈｐ感染的临床发病与Ｈｐ的ｖａｃＡ基因型，具有ｃａｇＡ基因Ｈｐ以及ＶａｃＡ和ＣａｇＡ蛋白的表达有着密切的关系。     

幽门螺杆菌空泡毒素活性与相关胃肠疾病的研究

幽门螺杆菌 (Ｈｐ)在发展中国家人群中的感染率高 ,与慢性胃炎、消化性溃疡和黏膜相关淋巴组织淋巴瘤的发生发展有密切关系。ＨｐｖａｃＡ基因表达产物为能使上皮细胞产生空泡变性的毒蛋白 ,称为空泡毒素 (ＶａｃＡ)。 1995年Ａｌｔｈｅｒｔｏｎ等[1] 发现 ,ｖａｃＡ基因有不同的基因表型。我们曾分析中国 (上海 )幽门螺杆菌ｖａｃＡ基因表型以Ｓ1ａ/ｍ2为主 ,与相关胃肠疾病无明显相关性[2 ] 。本研究 ,进一步通过体外细胞毒试验分析不同型ＶａｃＡ的空泡毒活性 ,探讨其与胃十二指肠疾病的关系。材料与方法一、临床资料1997年 6月至 1998年…     

消化性溃疡及胃癌患者血清CagA VacA抗体研究

细胞毒素相关蛋白（ｃｙｔｏｔｏｘｉｎａｓｓｏｃｉａｔｅｄｐｒｏｔｅｉｎ，ＣａｇＡ）和空泡形成毒素（ｖａｃｕｏｌａｔｉｎｇｃｙｔｏｔｏｘｉｎ，ＶａｃＡ）是幽门螺杆菌（Ｈｐ）相应的ＣａｇＡ，ＶａｃＡ基因编码产生的两种蛋白质，是Ｈｐ的重要致病因子，也作为Ｈｐ毒力分型的标志［１］，与消化性溃疡（ＰＵ）、胃癌有密切关系［２，３］，由于Ｈｐ菌株类型的分布存在明显的地区差异［４，５］．我们检测了本地区ＰＵ和胃癌患者的血清ＣａｇＡ，ＶａｃＡ抗体，旨在探讨我国东南沿海地区ＣａｇＡ，ＶａｃＡ与ＰＵ及胃癌的关系．１　…     

上海人幽门螺杆菌vac A基因表型与相关胃肠疾病

目的 探讨用ｖａｃＡ基因表型检测对幽门螺力（Ｈｐ）进行分型,并分析不同基因型与相关胃肠疾病之间的关系,方法 对临床胃黏膜标本中Ｈｐ菌株进行分离培养及其总ＲＮＡ抽提,逆转录聚合酶链反应检测ｖａｃＡ基因表型,结果 ５０株临床分离Ｈｐ菌株ｖａｃＡ基因表型ｓｌ／ｍ２型４６株（２％）ｓｌ／ｍｌ型４株（８％）,未发现ｓ２型,结论 上海人Ｈｐ菌株ｖａｃＡ基因绝大多数表达ｓ１／ｍ２型,ｓｌ／ｍ２基因表型分布于所有     

幽门螺杆菌vacA基因分型与毒素活性关系的研究进展

ｖａｃＡ基因编码ＶａｃＡ毒素是幽门螺杆菌产生的重要毒力因子，使细胞发生空泡变性，ｖａｃＡ基因信号序列和中区序列的不同可在各菌株间表现为五种不同的基因表现型，各型与毒素的活性关系密切，主要是由于不同细胞表面有针对毒素的各型特异性受体，ＶａｃＡ毒素显示了这两个不同的受体结合点。     

幽门螺杆菌致病因子与胃粘膜病理变化的关系

在众多幽门螺杆菌 (Ｈｅｌｉｃｏｂａｃｔｅｒｐｙｌｏｒｉ,Ｈｐ)的感染者中 ,仅少部分发展为消化性溃疡、胃癌或粘膜相关淋巴样组织淋巴瘤 (ｍｕｃｏｓａａｓｓｏｃｉａｔｅｄｌｙｍｐｈｏｉｄｔｉｓｓｕｅｌｙｍｐｈｏｍａ ,ＭＡＬＴｏｍａ)等较为严重的疾病 ,这促使了人们对Ｈｐ致病因子及致病机理的研究。在Ｈｐ的致病因子中 ,空泡形成毒素(ｖａｃｕｏｌａｔｉｎｇｃｙｔｏｔｏｘｉｎ ,ＶａｃＡ)、细胞毒素相关蛋白 (ｃｙｔｏｔｏｘｉｎａｓｓｏｃｉａｔｅｄｐｒｏｔｅｉｎ ,ＣａｇＡ)是最早发现的并非存在于所有Ｈｐ的蛋白 ,它们的致病…     

具有cagA,vacA基因的幽门螺杆菌感染与胃,十二指肠疾…

为初步探讨南京地区具有ｃａｇＡ，ｖａｃＡ基因幽门螺杆菌的感染状况以及ｃａｇＡ，ｃａｃＡ基因的存在与表达和胃，十二指肠疾病的关系，利用ＰＣＲ技术扩增ｃａｇＡ，ｖａｃＡ基因，对１０４份临床分离Ｈｐ基因进行检测分析。结果：（１）消化性溃疡患者ｃａｇＡ＾＋，ｖａｃＡ＾＋Ｈｐ感染率高于慢性胃炎患者，（２）ｃａｇＡ＾＋组胃炎炎症的急性活动程度重于ｃａｇＡ＾－组，而ｃａｇＡ＾＋组肠上皮化生率与ｃａｇＡ＾－组间无     

幽门螺杆菌VacA+株感染与消化疾病关系

为了解重庆地区幽门螺杆菌（Ｈｅｌｉｃｏｈａｃｔｅ，ｐｙｌｏｒＩ，Ｈｐ）ＶａｃＡ＋株感染与不同消化疾病的关系，本研究采用细胞培养方法调查了消化科住院患者ＨｐＶａｃＡ”株感染情况１材料和方法１．１材料①４２株Ｈｐ菌来自我校西南医院消化科４８例住院患者，其中胃溃疡１８例，十二指肠溃疡１２例，慢性胃炎８例，胃癌１０例首次分离Ｈｐ菌采用牛心、脑浸液固体培养基，微需氧、３７℃培养４８ｈ②革兰染色观察形态，尿素酶、氧化酶、过氧化氢酶试验鉴定Ｈｐ菌③用设计方法收集ＶａｃＡ空泡毒素，ｖａｃｕｏｌａｔｉｎｇ　ｃｙｔ…     

重视对幽门螺杆菌感染临床结局多样性的研究

幽门螺杆菌(Ｈｐ)在人群中的感染率高达40%～60%,感染后可产生不同结局:多数仅有不同程度的慢性胃炎,10%～15%可发生消化性溃疡,极少数可发生胃恶性肿瘤。阐明Ｈｐ感染致病多样性的机制对于Ｈｐ感染预后的判断和临床防治有重要意义,对其机制的探讨成了Ｈｐ研究中的新热点,现就此问题作一简述。一、Ｈｐ因素Ｈｐ的致病性与其毒力因子有关,后者主要由其基因型所决定。Ｈｐ菌株的基因型存在着显著多态性,与其致病性有密切的关系,是造成Ｈｐ感染后不同临床结局的重要因素。1空泡毒素Ａ(ＶａｃＡ)和细胞毒相关基因(ＣａｇＡ)蛋白:ＶａｃＡ和Ｃａ…     

Helicobacter pylori vacuolating cytotoxin, VacA

Helicobacter pylori is the leading bacterial cause of food-borne illness worldwide and plays a major role in the development of chronic gastritis, peptic ulcer, and gastric cancer. Strains isolated from patients contain the cagA gene (cytotoxin-associated gene A) and produce the vacuolating cytotoxin, VacA. Recent molecular and cellular studies of VacA action have begun to unravel its structure and the details of the mechanism of gastric injury caused by H. pylori infection.     

Helicobacter pylori cagA, iceA and vacA status in Taiwanese patients with peptic ulcer and gastritis

BACKGROUND: Helicobacter pylori causes chronic gastritis, peptic ulcer, gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. Different genotypes of H. pylori are confirmed from diverse geographical areas. Its association with clinical diseases remains controversial. The aim of the present study was to investigate the H. pylori vacuolating cytotoxin (vacA) alleles, cytotoxin-associated gene (cagA) and iceA, in patients with peptic ulcer and gastritis. METHODS: We enrolled patients with peptic ulcer and chronic gastritis. Biopsy specimens were obtained from the antrum and lower body of the stomach. DNA extraction and polymerase chain reaction (PCR) were used to detect the presence or absence of cagA and to assess the polymorphism of vacA and iceA. RESULTS: A total of 133 patients (57 gastric ulcer, 52 duodenal ulcer, 24 chronic gastritis) had positive PCR results from biopsy specimens. Concerning genotypes, we found cagA (79% in the antrum, 92% in the body) and iceA1 (73% in the antrum, 82.8% in the body) strains in the majority of patients. The dominant vacA subtype was s1a (74.4% in the antrum, 75% in the body), followed by s1c (51.1% in the antrum, 60.5% in the body). In the middle region, the m2 strain dominated (49.6% in the antrum, 41.4% in the body), followed by m1T (19.5% in the antrum, 9.5% in the body). Mixed infection occurred in 89 patients (67%). There was no statistical difference in genotypes among the three groups. CONCLUSION: In Taiwan, H. pylori with positive cagA and iceA1 was found in the majority of cases. H. pylori with vacA s1a strains was the most common vacA subtype, followed by s1c, while s1b was rare. In the middle region, the m2 subtype was predominant followed by m1T. There was no significant association between genotypes and clinical diseases.     

Helicobacter pylori vacA genotypes and cagA status and their relationship to associated diseases

Helicobacter pylori (H. pylori ) is a major causativebacterium of chronic gastritis, peptic ulcer and mucosaassociated lymphoid tissue lymphoma in humans, and associated with an increased risk of gastric cancer[1 -8]. An important virulant factor of H. pylori is the vacuolating cytotoxin ( VacA ) encoded by vacA that induces cytoplasmic vacuolation in target cells both in vitro and in vivo[9-11]. VacA is produced as a 140 kDa precursor which contains an N-terminal signal peptide and an approximately 33 kDa C-terminal outer membrance exporter. The precursor is cleaved at both N-terminal and C-terminal and secreted into the extracellular milieu as a 95 kDa mature protein. The mature protein futher undergoes specific cleavage to yield 37 kDa and 58 kDa subunits[12-14] Although vacA is present in all H. pylori strains, only about 50% to 60% of strains can induce vacuolation of epithelial cells as assessed by the HeLa cell assay. vacA shows considerable genetic variation in H. pylori isolated from all over the world and contains at least two variable regions. The s region exists as sl or s2 allelic types. Among type sl strains, subtypes sla and slb have been identified. The m region occurs as ml or m2 allelic types. Specific vacA genotype of H. pylori strains are associated with the production of the cytotoxin in vitro, epithelial damage in vivo, and clinical consequences[15-27]. The other virulant factor is the cytotoxin-associated protein (CagA) encoded by the cytotoxin-associated gene (cagA). The cagA gene is present in about 60% to 70% of strains and all of these strains express the cagA. The presence of cagA is also associated with the production of the cytotoxin in vitro, and clinical outcome[24-30]. The aim of this study was (i) to identify vacA genotypes and cagA status of H. pylori isolated from Chinese patients; (ii) to evaluation the relatioship beween vacA genotypes, cagA status and related gastroenterological disorders.     

湖北地区幽门螺杆菌VacA基因分型及疾病相关性分析

目的了解湖北地区幽门螺杆菌（Hp）空泡毒素基因（vacA）不同噩型及其与慢性胃炎（CG）和慢性消化性溃疡（CPU）之间的相关性。方法采用共享引物PCR技术和特异的PCR分型引物，对74例CG或CPU患者胃黏膜活检组织Hp分离株进行分型，并分析不同亚型与这两种疾病的相关性。结果湖北地区的HpvacA基因主要以S1a—m2型为主，vacA的优势亚型分布与上海和广州相似．除了s2型以外，sla—ml、S1b—m1、s1b—m2、s1c—m1和S1c—m2均有分布；另有8株不能被完全分型。结论湖北地区Hp vacA基因的不同亚型与CG和CPU之间不存在相关性，CG和CPU的引发因素有待进一步研究。     

幽门螺杜菌cagA,vacA基因的调查及其临床意义

目的 调查广州地区患者感染幽门螺杆菌（Ｈｐ）的细胞毒素相关基因（ｃａｇＡ）及空泡毒素基因（ｖａｃＡ）亚型的流行情况,探讨Ｈｐ ｃａｇＡ及ｖａｃＡ亚型与Ｈｐ相关性胃肠疾病间的关系。方法 自广州地区不同疾病患乾胃黏膜中分离得到１９１株Ｈｐ,抽提各株菌的总ＤＮＡ,采用特定引物对各株菌ｃａｇＡ３’端、ｖａｃＡ中间序列（ｍ）及信号序列（ｓ）进行ＰＣＲ检测。结果 广州地区Ｈｐ ｃａｇＡ阳性者占８５．３％（１６     

Helicobacter pylori vacA genotypes and cagA gene in a series of 383 H. pylori-positive patients

BACKGROUND: Only 10-15% of all patients infected with Helicobacter pylori develop peptic ulcer disease (PUD) or gastric cancer. Apart from immunological factors in the host, virulence determinants of H. pylori such as the vacuolating cytotoxin (VacA) or the cytotoxin-associated protein A (CagA) might represent a predisposition for the development of PUD. METHODS: We studied antral biopsies of 383 H. pylori-positive patients with peptic ulcer disease (PUD) or other H. pylori-related diseases for H. pylori vacA genotypes and the presence of the cagA gene by PCR. RESULTS: VacA genotypes and cagA status could be completely determined in 357 (93.2%) of the patients. In 91 (93.8%) of 97 patients with PUD, the vacA s1 genotype (s1m1, 45; s1m2, 46 patients) was present. The vacA s2m2 genotype was found in only 6 (6.2%) of 97 patients with PUD. In contrast, 180 (75.3%) of 239 patients (s1m1, 89; s1m2, 91 patients) without PUD and without gastric malignancies harbored strains with the vacA s1 genotype. The vacA genotype s2m2 was found in 59 (24.7%) of these patients. The presence of the cagA gene was closely associated with the vacA genotype s1 and found in 124 (88.6%) and in 113 (80.7%) of patients with the s1m1 or s1m2 genotypes, respectively, whereas strains with the genotype s2m2 were almost exclusively cagA negative. CONCLUSION: Most H. pylori strains found in patients with PUD possess the vacA s1 genotype and the cagA gene. Patients with this type of H. pylori strain but without PUD might be at higher risk of developing PUD. In contrast, the risk for PUD might be significantly decreased in those patients who are infected by H. pylori strains with the vacA s2 genotype lacking the cagA gene.     

Genetic analysis and clinical evaluation of vacuolating cytotoxin gene A and cytotoxin-associated gene A in Taiwanese Helicobacter pylori isolates from peptic ulcer patients

The aims of this study were to investigate the cytotoxin-associated gene A (cagA) and vacuolating cytotoxin gene A (vacA) subtype in Taiwanese H. pylori isolates from patients with gastroduodenal diseases and to assess the relationship between genotypes of isolates and clinical features. The vacA s1a allele was found in all isolates and vacA m1 allele was found in 15% of isolates. The cagA gene was found in 82.5% of isolates. The vacA s1a/m2 strains had a significantly higher prevalence rate than vacA s1a/m1 strains in Taiwan (p < 0.05). By aligning and comparing the nucleotide and amino acid sequences of vacA from the Taiwanese isolates, the signal sequence and N-terminal region were found to be highly conserved, but the middle region was found to be highly heterogeneous. Determining the relationship between the genotypes and clinical features, we found that the cagA gene was more closely associated with duodenal ulcer than with gastric ulcer and the vacA s1a/m2 strain was more closely associated with active chronic gastritis and atrophic gastritis than with chronic gastritis. Together, our results indicated that (i) the middle region of vacA gene in Taiwanese isolates was heterogeneous; (ii) s1a/m2 vacA strains had a high prevalence in Taiwanese peptic ulcers; and (iii) the cagA gene was significantly associated with duodenal ulcer.     

Genotypes of Helicobacter pylori in patients with peptic ulcer bleeding

AIM: Helicobacter pylori causes chronic gastritis, peptic ulcer, gastric cancer and MALT-lymphoma. Different genotypes of Helicobacter pylori are confirmed from diverse geographic areas. Its association with bleeding peptic ulcer remains controversial. The aim of this study was to investigate the Helicobacter pylori vacA alleles, cagA and iceA in patients with bleeding peptic ulcer. METHODS: We enrolled patients with bleeding, non-bleeding peptic ulcers and chronic gastritis. Biopsy specimens were obtained from the antrum of the stomach for rapid urease test, bacterial culture and PCR assay. DNA extraction and polymerase chain reaction were used to detect the presence or absence of cagA and to assess the polymorphism of vacA and iceA. RESULTS: A total of 168 patients (60.4%) (25 patients with chronic gastritis, 26 patients with bleeding gastric ulcer, 51 patients with non-bleeding gastric ulcer, 26 patients with bleeding duodenal ulcer, and 40 patients with non-bleeding duodenal ulcer) were found to have positive PCR results between January 2001 and December 2002. Concerning genotypes, we found cagA (139/278, 50%), vacA s1a (127/278, 45.7%), and ice A1 (125/278, 45%) predominated in all studied patients. In patients with bleeding peptic ulcers, vacA s1a and m1T were fewer than those in patients with non-bleeding peptic ulcers (37/106 vs 69/135, P=0.017, and 4/106 vs 21/135, P =0.002). CONCLUSION: In patients with peptic ulcers, H pylori vacA s1a and m1T prevent bleeding complication.     

Helicobacter pylori cagA, iceA and vacA genotypes in patients with gastric cancer in Taiwan

AIM: Helicobacter pylori (H pylori ) has been linked to chronic gastritis, peptic ulcer, gastric cancer and MALT-lymphoma. The link of genotypes of H pylori to gastric cancer remains controversial. The aim of this study was to investigate the H pylori vacA alleles, cagA and iceA in patients with gastric cancer in Taiwan. METHODS: Patients with gastric cancer, peptic ulcer and chronic gastritis were enrolled in this study. We obtained biopsy specimens from the stomach at least 2 cm away from the tumor margin in patients with gastric cancer, and from the antrum of stomach in patients with peptic ulcer or chronic gastritis. DNA extraction and polymerase chain reaction were used to detect the presence or absence of cagA and to assess the polymorphism of vacA and iceA. RESULTS: A total of 168 patients (gastric ulcer: 77, duodenal ulcer: 66, and chronic gastritis: 25) were found to have positive PCR results of the biopsy specimens from patients with peptic ulcer and chronic gastritis. We found positive cagA (139/168, 83%), m2 (84/168, 50%) and iceA1 (125/168, 74%) strains in the majority of patients. In patients with gastric cancer, the vacA s1a and s1c subtypes were less commonly found than those in non-cancer patients (35/66 vs 127/168, P = 0.0001 for s1a and 13/66 vs 93/168, P<0.0001 for s1c). In the middle region, the m1T strain in patients with gastric cancer was more than that of non-cancer patients (23/66 vs 33/168, P = 0.02). CONCLUSION: In Taiwan, H pylori with positive vacA s1a, cagA and iceA1 strains are found in the majority of patients with gastric cancer or non-cancer patients. In patients with gastric cancer, the vacA s1a and s1c subtypes are less and m1T is more than in patients with peptic ulcer and chronic gastritis.