幽门螺杆菌CagA基因株致病机理及与胃十二指肠疾病的关系

幽门螺杆菌（Ｈｐ）的毒力决定其致病能力。感染了Ｈｐ的人群大部分无症状，只有少数人表现不同程度的症状，可能是感染了不同毒力的菌株所致。有细胞毒相关蛋白（ＣａｇＡ）基因的均为高毒株，与消化性溃疡、萎缩性胃炎、胃癌密切相关。对ＣａｇＡ＾＋株深入研究有助于加深对Ｈｐ致病机理的认识。     

延边地区幽门螺杆菌与胃十二指肠疾病

幽门螺杆菌（Ｈｅｌｉｃｏｂａｃｔｅｒｐｙｌｏｒｉ,Ｈｐ）在胃十二指肠疾病发病中的作用已明确．我们研究Ｈｐ与组织活检观察延边地区Ｈｐ与胃十二指肠疾病性质、类型、程度的关系．１　材料和方法１．１　材料　我院１９９３０１／１９９９０２做内镜取胃粘膜活检标本１９９１例,６８７２组织块．男９９８例,女９９３例,年龄１２岁～８１岁,平均４２岁．取材部位胃窦部１８５０例,胃体１９０例,贲门６６例．１．２　方法　一般在不同部位取３块～４块组织,１块用ＨｐＵＴ试剂盒（福建三强生物化工有限公司提供）检测Ｈｐ,其…     

胃液中维生素C与幽门螺杆菌和胃十二指肠疾病

目的研究胃液中维生素Ｃ（ＶｉｔＣ）浓度与幽门螺杆菌（Ｈｐ）感染和胃、十二指肠疾病的关系。方法抽取病人空腹胃液和血液，用高铁还原法测定血浆和胃液中的ＶｉｔＣ浓度；Ｈｐ通过尿素酶试验和病理ＷＳ染色确定。结果Ｈｐ阳性病人胃液中ＶｉｔＣ浓度明显低于Ｈｐ阴性病人；胃液中ＶｉｔＣ浓度与慢性胃炎的炎症程度无关，但在活动性胃炎病人胃液中ＶｉｔＣ浓度明显低于非活动性胃炎病人；与非溃疡性消化不良病人相比，活动期胃溃疡和十二指肠溃疡病人的ＶｉｔＣ浓度明显降低。结论Ｈｐ感染可导致胃液中ＶｉｔＣ浓度降低，这可能是Ｈｐ与胃癌和消化性溃疡的发生相关联的重要因素     

幽门螺杆菌CagA基因株致病机理及与胃十二指肠疾病的关系

幽门螺杆菌(Hp)的毒力决定其致病能力。感染了Hp的人群大部分无症状,只有少数人表现不同程度的症状,可能是感染了不同毒力的茵株所致。有细胞毒相关蛋白(CagA)基因的均为高毒株,与消化性溃疡、萎缩性胃炎、胃癌密切相关。对CagA~+株深入研究有助于加深对Hp致病机理的认识。     

儿童胃幽门螺杆菌感染与上胃肠道疾病

目的：研究儿童胃幽门螺杆菌（ＨＰ）感染的特点，以及与上胃肠病的关系。方法：对１５３例因胃肠症状接受胃镜检查的有连续症状的患儿进行前瞻性、活检组织学、血清学、尿素酶法检查、并与２６５例成年患者及１８１例无症状健康儿童对照。结果：患儿ＨＰ感染率２９％，低于成年患者７１％（Ｐ＜００５），与健康儿童（３４％）无差异（Ｐ＞００５）。儿童消化性溃疡ＨＰ感染６８％，高于非溃疡组２２％（Ｐ＜００５），但显著低于成人组９８％（Ｐ＜００５）。ＨＰ相关胃炎儿童内镜无特征、组织学炎症细胞浸润活动明显。结论：儿童ＨＰ感染是溃疡致病因素，但非唯一因素，ＨＰ感染和症状无关，ＨＰ相关胃炎有一定组织学特点。     

幽门螺杆菌与上消化道疾病关系的研究

幽门螺杆菌（Ｈ．ｐｙｌｏｒｉ）是一种螺旋形细菌。１９８３年澳大利亚学者Ｗａｒｒｅｎ和Ｍａｒｓｈａｌｌ首先分自成功Ｈ．ｐｙｌｏｒｉ,并提出其可能是人类慢性胃炎的病原菌,从而引起各国学者对Ｈ．ｐｙｌｏｒｉ研究的重视。通过十多年的大量研究,已经基本确定Ｈ．ｐｙｌｏｒｉ与４种上消化道疾病密切相关：①慢性胃炎;②消化性溃疡;③胃粘膜相关淋巴组织（ＭＡＬＴ）淋巴瘤;④胃癌。目前对Ｈ．ｐｙｌｏｒｉ与功能性消化不良（ＦＤ）和胃息肉的关系尚无肯定意见。本文就近年Ｈ．ｐｙｌｏｒｉ相关性上消化道疾病研究的新进展作一介…     

胃幽门螺杆菌感染与慢性胃炎镜下表现和消化性溃疡关系的探讨

本文报道用快速尿素酶试验法分析的1 717例慢性胃十二指肠疾病的胃幽门螺杆菌(Helicobacter pylori,HP)的感染情况。结果显示皱襞增粗型胃炎、充血/渗出型胃炎、扁平糜烂型胃炎、隆起糜烂型胃炎、胆汁反流型胃炎、出血型胃炎、皱襞萎缩型胃炎的HP感染率分别为70.00％,49.72％,48.86％,47.37％,41.94％,38.1％,34.48％,但无显著性差异。十二指肠溃疡HP感染率高达71.11％,显著高于胃溃疡的60.83％。男性病人HP感染率为47.8％,显著低于女性病人的63.7％。这表明慢性胃炎胃镜下形态学差异与幽门螺杆菌感染率高低无关,十二指肠球部溃疡与HP感染的关系较胃溃疡者更为密切,人群中HP感染存在性别差异。     

幽门螺杆菌动物模型应用进展

在幽门螺杆菌（Hp)研究中,动物模型应用于：（1）构建Hp相关疾病模型;（2）评价Hp疫苗作用,本文综述了Hp动物模型在以上两方面的应用进展。     

十二指肠胃反流和幽门螺杆菌感染关系研究

目的：探讨消化性溃疡患者中的十二指肠胃反流对幽门螺杆菌（Hp)感染的影响。方法：70例消化性溃疡患者，用核素^99MTC-EHIDA测定十二指肠胃反流，胃黏膜Giemsa染色后检测Hp和双抗体夹心ELISA法测定血清Hp-IgG水平。结果：在42例十二指肠胃反流阴性组中，Hp感染率为83．3％（35／42）；28例十二指肠胃反流阳性组中，Hp感染率为39．3％（11／28），两组间Hp感染率差异有显著性（P＜0．05）。而Hp阳性组46例患者中，十二指肠胃反流阳性率为30．4％（14／46）；Hp阴性组24例中，十二指肠胃反流率为58．3％（14／24），两组间十二指肠胃反流率差异也有显著性（P＜0．05）。结论：在消化性溃疡中，十二指肠胃反流对胃内Hp感染可能有抑制作用。     

Helicobacter pylori infection in children

Helicobacter pylori was sought prospectively by culture of antral biopsy, histology and serology (IgG and IgA) in 440 consecutive endoscopies on children to determine the prevalence, clinical presentation and histological features of H. pylori infection in our population. Twenty-eight patients had H. pylori (8% overall). The mean age of infected patients was significantly higher than that of non-infected patients (P less than 0.0001). No patient under 5 years of age had H. pylori isolated. Overall, there was no significant difference in clinical presentation between those with and those without H. pylori infection, but 23% of patients 5 and 26 years of age who presented with abdominal pain as the indication for their endoscopy had H. pylori isolated. Macroscopic changes ranged from no abnormality to frank ulceration, but the typical antral mamilliform changes were 100% predictive of infection. Fifty-eight per cent of patients with duodenal ulcers, but only 17% with gastric ulcers had H. pylori infection. Histological gastritis was present in 144 patients (including all H. pylori positive patients). None of the patients with another definable cause for gastritis had H. pylori isolated. In conclusion, H. pylori is an important cause of primary gastritis in our population, occurring in children over 5 years of age. Culture of an antral biopsy should be performed in children over this age undergoing endoscopy for the investigation of abdominal pain and, more particularly, in those with peptic ulceration.     

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.     

幽门螺杆菌不是慢性胃病的主要致病因素——附378例临床调查报告

[目的]验证幽门螺杆菌（Hp）是否为慢性胃病的主致病因素。[方法]用概率、构成比、相对比对378例慢性胃病患者进行统计分析。[结果]慢性活动性胃炎213例,Hp阳性概率为0．2535,Hp阳性例数构成比为25．35％;Hp阴性概率为o．7465,Hp阴性例数构成比为74．65％,Hp阴性例数与Hp阳性例数的相对比为2．94（倍）。溃疡病（A1期）165例,Hp阳性概率为0．4061,Hp阳性例数构成比为40．61％;Hp阴性概率为0．5939,Hp阴性例数构成比为59．39％,Hp阴性例数与Hp阳性例数的相对比为1．46（倍）。[结论]Hp不是胃炎及溃疡病的主致病因素,Hp可能对胃黏膜屏障起保护作用。     

胃窦部幽门螺杆菌清除对萎缩性胃炎病理改变的影响

目的通过对幽门螺杆菌（Hp）相关的萎缩性胃炎病人Hp清除治疗前后胃窦部黏膜病理改变的分析，来确定Hp对其炎症程度、活动性（中性粒细胞浸润）、腺体萎缩和肠上皮化生的影响。方法106例Hp相关的萎缩性胃炎患者接受Hp清除治疗，对其治疗前后胃窦部黏膜的病理变化进行分析，分析标准按96悉尼系统评定。结果在62例治疗成功组中，治疗后胃黏膜的炎症程度及活动性较治疗前明显减轻，但腺体萎缩及肠上皮化生未减轻。在44例治疗失败组中，治疗前后胃黏膜的炎症程度、活动性、腺体萎缩及肠化均没有变化。且随着Hp感染时间的延长，腺体萎缩和肠化还可加重。结论Hp的清除治疗可使萎缩性胃炎患者胃黏膜的炎症程度及活动度减轻，对此类病人应行Hp清除治疗。     

Role of Helicobacter pylori infection in pernicious anaemia.

Background. Pernicious anaemia is associated with atrophic body gastritis and considered an autoimmune disease. Whether Helicobacter pylori is involved in the induction of pernicious anaemia is uncertain.

Aims. To investigate the prevalence of Helicobacter pylori infection in pernicious anaemia patients and to ascertain whether the Helicobacter pylori positive patients had distinctive clinical and gastric morphofunctional characteristics.

Patients and Methods. A series of 81 consecutive pernicious anaemia patients underwent serological, functional and endoscopic/histological investigations.

Results. A total of 49 (60.5%) patients were Helicobacter pylori-positive (males 61.2% vs females 38.8%). No difference was observed in clinical and morphofunctional characteristics between Helicobacter pylori-positive and negative patients, whereas distinctive functional/histological features between histologically Helicobacter pylori-positive (n=8) and serologically Helicobacter pylori-positive (n=41) cases were detected. In the histologically Helicobacter pylori-positive group, Pepsinogen I was higher [13 [0–58] vs 5 [0–26] ng/ml; P=0.0025]) and positivity for anti-parietal cell antibodies was lower [42.9% vs 76.9, P=0.0867). Antral histological variables of the gastritis score were significantly higher in the histologically Helicobacter pylori-positive than in the serologically Helicobacter pylori-positive patients, but this latter group had a higher score of body atrophy (2.63± 0.12 vs 1.71 ± 0.29; P=0.0051). Body inflammation was also significantly higher in the histologically Helicobacter pylori-positive group (chronic inflammation: 1.43±0.2 vs 1.05±0.06; P=0.0271; inflammation acitivity:: 0.57±0.3 vs 0.15±0.06, P=0.0220). Antral mucosa was normal in 24/41 (58.5%) of the serologically Helicobacter pylori-positive patients, but only in 1/8 (12.5%) of the histologically Helicobacter pylori-positive patients (p=0.232).

Conclusions. Almost two thirds of pernicious anaemia patients have evidence of Helicobacter pylori, but only those with an active Helicobacter pylori infection have distinctive functional and histological features. These findings support the hypothesis that Helicobacter pylori infection could play a triggering role in a subgroup of pernicious anaemia patients.     

中西医结合根除幽门螺杆菌对萎缩性胃炎核因子-κB表达的影响

[目的]观察以胃舒散为主的三联疗法（胃舒散、呋喃唑酮和克拉霉素）治疗幽门螺杆菌（Hp）阳性慢性萎缩性胃炎（CAG）的临床效果及其对核因子-κB（NF-κB）表达的影响。[方法]41例Hp阳性CAG患者服用胃舒散2．0g，呋喃唑酮0．1g，各3次／d，克拉霉素0．25g，2次／d，1周后再继服胃舒散4周。治疗前及治疗结束1年后行内镜及病理组织学检查，取活检观察病理组织学改变及NF-κB表达变化，采用银染色法、^14C-尿素呼气试验或快速尿素酶试验检测Hp。[结果]三联疗法结束1年后，Hp根除率为85．4％；根除Hp能显著减轻患者胃窦部慢性炎症（P〈0．05）和活动程度（P〈0．01），下调NF-κB表达（P〈0．01），但胃炎的萎缩和肠化生等病理无明显改变。[结论]以胃舒散为主的三联疗法对Hp有较高根除率。根除Hp可抑制NF-κB的表达，减轻活动性炎症，但近期观察对萎缩、肠化生等病理改变无明显作用。     

Helicobacter pylori infection and gastritis: the Systematic Investigation of gastrointestinaL diseases in China (SILC)

Background and Aim: Helicobacter pylori infection remains common in East Asia, though its prevalence is decreasing in Western countries. H. pylori‐related atrophic gastritis (AG) may reduce the likelihood of gastroesophageal reflux disease (GERD). We investigated the prevalence of H. pylori infection and AG and their association with endoscopic findings and symptom‐defined GERD in Shanghai. Methods: A representative random sample of 3600 Shanghai residents aged 18–80 years was invited to complete a general information questionnaire and a Chinese version of the Reflux Disease Questionnaire, to provide blood samples for H. pylori serology and pepsinogen (PG) I/II assay (to detect AG, defined as PGI < 70 µg/L and/or PGI/PGII < 7), and to undergo endoscopy. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by multivariate logistic regression. Results: A total of 1022 Shanghai residents underwent endoscopy and were valid for inclusion in the study. Of these, 71.7% tested positive for H. pylori, 63.8% had AG and 30.5% had moderate/severe AG (PGI < 50 µg/L and/or PGI/PGII < 5). Helicobacter pylori infection was equally common in all age groups. Severity of AG increased with age in women. Reflux esophagitis was inversely associated with AG (OR, 0.23 [CI, 0.09–0.55] for moderate/severe AG compared with no H. pylori or gastritis). However, symptom‐defined GERD showed no clear association with AG. Conclusions: Helicobacter pylori infection and AG are very common in Shanghai, and the infection is acquired early in life. Atrophic gastritis is inversely associated with reflux esophagitis but is not significantly associated with symptom‐defined GERD.     

Cytotoxin and urease activities of Helicobacter pylori isolates from Japanese patients with atrophic gastritis or duodenal ulcer

The vacuolating cytotoxin and urease secreted by Helicobacter pylori are thought to be virulent factors. Because vacuolation is potentiated by the presence of ammonium ion, which is produced by urease in vitro, it is of interest to examine whether cytotoxin and urease work reciprocally in the development of atrophic gastritis or duodenal ulcer. In the present study, patients (all H. pyloripositive) were divided into four groups: mild atrophic gastritis (group 1; nine patients), severe atrophic gastritis (group 2; 36 patients), duodenal ulcer with mild atrophic gastritis (group 3; 19 patients) and duodenal ulcer with severe atrophic gastritis (group 4; 12 patients). Cytotoxin production and urease activity of H. pylori isolated from these patients were analysed. Cytotoxin production was observed in four of nine (44.4%), 28 of 36 (77.8%), 11 of 19 (57.9%) and eight of 12 (66.7%) isolates from groups 1, 2, 3 and 4, respectively. Cytotoxin-producing H. pylori isolates were found significantly more in patients with severe atrophy than in patients with mild atrophy (P= 0.048). The mean of relative activity of cytotoxin in H. pylori isolate was 1. 6. ± 2. 3, 7. 9. ± 7. 4, 5. 8. ± 6. 0 and 9. 0 ± 9. 1 in groups 1, 2, 3 and 4, respectively. Helicobacter pylori isolates from severe atrophy or duodenal ulcer patients in groups 2 or 4 possessed significantly higher activity than those from non-ulcer patients in group 1 (P= 0.017 and 0.030, respectively). The mean of urease activity was 8. 6 ± 4. 6, 10. 0 ± 5. 9, 10. 0 ± 8. 5 and 11. 2 ± 7. 7 IU/mg in groups 1, 2, 3 and 4, respectively. These differences indicated no statistical significance. In each H. pylori isolate, the production of cytotoxin and urease were independent, which indicated that there was no reciprocal effect between them in vivo. Thus, cytotoxin-producing H. pylori isolates were more prevalent in patients with severe atrophic gastritis and the cytotoxin activities of H. pylori isolates from the patients with severe atrophic gastritis or duodenal ulcer were much higher than those from the patients with mild atrophic gastritis, which suggested that vacuolating cytotoxin may be a disease-inducing factor.     

Association of Helicobacter pylori infection with atrophic gastritis and intestinal metaplasia

AIMS: To evaluate the effect of Helicobacter pylori infection and aging on atrophy and intestinal metaplasia of the gastric mucosa. METHODS: One hundred and sixty-three patients were divided into three age groups and underwent an upper gastrointestinal endoscopy where no esophagitis, peptic ulcers, or malignancies were detected. Two biopsy specimens were obtained from the anterior and posterior walls of the antrum and of the fundus. These were used to evaluate the grade of gastritis, bacterial culture and histologic evidence of H. pylori infection. RESULTS: Helicobacter pylori infection was found to be directly associated with an increased risk of gastritis grade (odds ratio (OR) = 90 (95% CI; 30-270)). An age of 60 years and older along with H. pylori infection was also strongly associated with an increased risk of atrophy (OR = 6.6, (95% CI; 2.9-15.2)); OR = 9.8, (95% CI; 2.7-35.4)), as was intestinal metaplasia of the gastric mucosa (OR = 5.5, (95% CI; 1.7-17.6)); OR = 7.9, (95% CI; 2.8-46.1)). The prevalence of atrophic gastritis increased with advancing age in H. pylori-infected patients, but no such phenomenon was observed in H. pylori-uninfected patients. The prevalence of intestinal metaplasia significantly increased with advancing age, irrespective of the presence of H. pylori infection. In addition, H. pylori uninfected female patients had a decreased risk of intestinal metaplasia. CONCLUSIONS: These results suggest that atrophic gastritis is not a normal aging process, but instead is likely to be the result of H. pylori infection, while intestinal metaplasia is caused by both the aging process and H. pylori infection. A decreased risk of intestinal metaplasia found in uninfected female subjects may partly explain the lower prevalence of gastric cancer in females than in males.     

Clinical significance of PCR in Helicobacter pylori DNA detection in human gastric disorders

ＣｌｉｎｉｃａｌｓｉｇｎｉｆｉｃａｎｃｅｏｆＰＣＲｉｎＨｅｌｉｃｏｂａｃｔｅｒｐｙｌｏｒｉＤＮＡｄｅｔｅｃｔｉｏｎｉｎｈｕｍａｎｇａｓｔｒｉｃｄｉｓｏｒｄｅｒｓＸＵＧｕｏＭｉｎｇ，ＪＩＸｕＨｕａｉ，ＬＩＺｈａｏＳｈｅｎ，ＭＡＮＸｉａｏＨｕａ...