Induction of gastric epithelial apoptosis by Helicobacter pylori.

BACKGROUND--Helicobacter pylori may promote gastric carcinogenesis through increasing gastric epithelial cell proliferation. How H pylori does so is unknown. Programmed, non-necrotic, cell death (apoptosis) occurs throughout the gut and is linked to proliferation. It was hypothesised that H pylori may induce hyper-proliferation through increasing apoptosis. AIM--To measure the effect of H pylori infection on gastric epithelial apoptosis in situ. PATIENTS--Patients with duodenal ulcers treated to eradicate H pylori and patients with H pylori negative non-ulcer dyspepsia. METHODS--Retrospective quantification of apoptotic epithelial cells in situ from formalin fixed biopsy specimens, counted after staining by terminal uridine deoxynucleotidyl nick end-labelling. RESULTS--In the uninfected stomach, apoptotic cells were rare and situated in the most superficial portion of gastric glands (mean 2.9% of epithelial cells). In H pylori infection, they were more numerous and were located throughout the depth of gastric glands, comprising 16.8% of epithelial cells, falling to 3.1% after H pylori eradication, p = 0.017. Apoptotic cell number did not correlate with the degree of histological gastritis. CONCLUSIONS--These results suggest that H pylori induces epithelial apoptosis in vivo. Increased apoptosis may be the stimulus for a compensatory hyperproliferative and potentially preneoplastic response in chronic H pylori infection.     

Increase in apoptosis and decrease in ornithine decarboxylase activity of the gastric mucosa in patients with atrophic gastritis and gastric ulcer after successful eradication of Helicobacter pylori

OBJECTIVE: Recent reports have shown that patients infected with Helicobacter pylori (H. pylori) have a higher risk of gastric cancer. However, the mechanism of this increased risk is still unclear. In the gastric mucosa, the size of a continuously renewed population of cells is determined by the rates of cell production and of cell loss. Ornithine decarboxylase (ODC) activity is elevated in various gastrointestinal cancers and serves as a marker of mucosal proliferative activity. Apoptosis occurs throughout the gut and is associated with cell loss. Both cell proliferation and cell loss have important roles in H. pylori-associated gastric carcinogenesis. Therefore, we investigated the effect of H. pylori eradication on ODC activity and apoptosis in the gastric mucosa of patients with atrophic gastritis and gastric ulcers. METHODS: Biopsy specimens of the gastric antrum were obtained at endoscopy from 17 H. pylori-positive gastric ulcers patients and 15 H. pylori-positive gastritis patients before and 4 wk after eradication therapy with amoxicillin, omeprazole, and a new anti-ulcer agent, ecabet sodium, and from 10 gastric ulcer patients in whom ulcer healed but H. pylori was left untreated. ODC activity and induction of apoptosis were determined immunohistochemically. RESULTS: H. pylori was successfully eradicated with the triple therapy in 12 (80%) of 15 gastritis patients and 13 (76%) of 17 gastric ulcer patients. ODC activity was present in the gastric mucosa in 21 (84%) patients before eradication but in only four (16%) patients after successful eradication (p = 0.0005). The apoptotic index increased significantly (p = 0.0006) from 4.2% +/- 0.4% before treatment to 7.4% +/- 0.5% after successful eradication. CONCLUSIONS: Successful eradication of H. pylori decreases mucosal ODC activity and increases apoptosis in the gastric mucosa. These findings indicate that by decreasing mucosal cell proliferation and increasing epithelial cell loss, H. pylori eradication may help decrease the subsequent risk of gastric cancer.     

Apoptosis in gastric epithelium induced by Helicobacter pylori infection: implications in gastric carcinogenesis

OBJECTIVES: Helicobacter pylori is an identified carcinogen for gastric cancer, however, the underlying mechanisms remain to be defined. In this review, we sought to elucidate the role of apoptosis in gastric carcinogenesis, to determine the influence of H. pylori infection on apoptosis, and finally to provide insights into the mechanisms by which H. pylori may lead to gastric carcinogenesis. METHODS: A broad-based MEDLINE and Current Contents literature search was performed to identify relevant publications between 1966 and March 2000 addressing H. pylori infection, apoptosis, cell proliferation, gastric carcinoma, oncogenes, and tumor suppressor genes, as well as the products of these genes. Abstracts from recent major conferences that provided adequate additional data were also included. RESULTS: Apoptotic cells are rare in the glandular neck region (the generative cell zone) of normal gastric mucosa. With progression of atrophic gastritis, the generative cell zone shifts downward and a relatively large number of apoptotic cells occur. In intestinalized glands, both apoptotic cells and proliferative cells are present in deeper portions of the glands, corresponding to the generative zone. A higher frequency of apoptosis has been observed in gastric dysplasia than in coexisting gastric carcinomas, whereas the number of proliferative cells is significantly higher in gastric carcinoma than in dysplasia. Upregulation of oncogene bcl-2 in premalignant lesions and "downregulation" of the gene after malignant change is probably a common event. Accumulation of p53 protein is first detected in dysplasia, although mutation of the pS3 gene may occur in intestinal metaplasia. H. pylori infection induces apoptosis in gastric epithelial cells, which returns to normal after eradication of the infection. Numerous molecules produced by H. pylori including cytotoxin (VacA), lipopolysaccharide, monochloramine, and nitric oxide may directly induce apoptosis. Moreover, H. pylori-stimulated host inflammatory/immune responses lead to release of a large amount of cytokines. Cytokines produced by type 1 T helper cells, such as TNF-alpha and IFN-gamma, markedly potentiate apoptosis. Gastric cell proliferation is significantly higher in patients with H. pylori infection than in normal controls, and eradication of the infection leads to a reduction in cell proliferation. Apoptosis and cell proliferation are also increased in precancerous lesions such as gastric atrophy, intestinal metaplasia, and dysplasia in the presence of H. pylori infection. However, H. pylori-induced apoptosis may no longer be cell cycle-dependent in these lesions because of the occurrence of alterations and mutations of apoptosis-regulating genes, resulting in a loss of balance between apoptosis and cell proliferation. CONCLUSIONS: It is hypothesized that H. pylori-induced apoptosis may play a key role in gastric carcinogenesis by increasing cell proliferation and/or resulting in gastric atrophy.     

TFF2在幽门螺杆菌感染胃体部黏膜中的表达

目的:探讨三叶因子2(TFF2)在幽门螺杆菌(H pylori)感染胃体腺黏膜中表达的意义.方法:选择有H pylori感染的胃手术切除标本29例(92个蜡块),其中胃及十二指肠溃疡5例,胃癌24例,用免疫组织化学方法检测TFF2的分布和表达.结果:在H pylori感染胃黏膜中,TFF2主要在胃体腺的颈黏液细胞和假幽门腺化生细胞中表达;在正常黏膜中TFF2主要分布在胃固有腺的上1/3-2/3;在轻度萎缩黏膜中,腺底部仅见少量阳性细胞,随着萎缩程度的加重,在腺底部出现的阳性细胞增多;在轻、中度萎缩黏膜中其强阳性率分别为18.0%和42.9%,而在重度萎缩中达90.5%.在轻、中度和重度萎缩之间有显著性差异(P<0.01).结论:H pylori感染增加在腺底部的TFF2表达,并与黏膜的萎缩程度有关.     

Helicobacter pylori induces apoptosis in mucosal lymphocytes in patients with gastritis

BACKGROUND: Previous studies suggest that Helicobacter pylori (H. pylori) induces apoptosis and compensatory hyperproliferation in gastric epithelial cells possibly explaining the carcinogenic capacity of the bacteria. The aim of this study was to measure the effect of H. pylori on apoptosis of gastric lymphoid cells in view of the development of gastric lymphoma. METHODS: 16 H. pylori-positive and 19 H. pylori-negative individuals were enrolled. Single cell suspensions were prepared from antral biopsies and apoptosis was measured by staining with the TUNEL-assay and the fluorochrome Hoechst 33342. Lymphocyte subsets were simultaneously identified by immunocytochemistry. RESULTS: The apoptotic index of all gastric mucosal cells was significantly higher in H. pylori-positive mucosa compared to negative controls. Additionally, H. pylori-infected patients showed a significant increase in apoptosis of mucosal B-lymphocytes. Apoptosis of T cells and plasma cells was unaffected by H. pylori. CONCLUSION: H. pylori induces apoptosis in mucosal B cells which might be important in the development of gastritis and possibly B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT).     

Implications of corpus gastritis, atrophy and cyclooxygenase in the development of gastric erosions after curing Helicobacter pylori infection

BACKGROUND: Helicobacter pylori eradication decreases recurrence of peptic ulcers with marked improvement in histological inflammation, but gastric mucosal injuries may be developed even after eradication. PURPOSE: To investigate the mechanisms responsible for the development of gastric erosions after eradication, we analysed the relationship between clinicopathological risk factors and the occurrence of gastric erosion after curing H. pylori infection. PATIENTS: Sixty patients underwent endoscopy before, and 3, 6 and 12 months after the completion of H. pylori eradication. METHODS: Risk factors associated with the development of gastric erosions after eradication were assessed by multivariate analysis, and cyclooxygenase-1 and -2 immunoreactivity was histologically examined in the gastric mucosa before and after eradication. RESULTS: The cumulative prevalence of gastric erosions after H. pylori eradication was 38.3% within 1 year. Using multivariate analysis, corpus gastritis scores (inflammation score+activity score), corpus atrophy scores and an age of more than 50 years were found to be independent factors associated with the development of gastric erosion after eradication with odds ratios of 7.39, 0.13 and 5.00, respectively. Cyclooxygenase-2 immunoreactivity of the corpus was decreased for the non-erosion group after eradication, but not for the erosion group. CONCLUSIONS: Severe gastritis or less severe atrophy in oxyntic glands but not in pyloric glands before eradication may be involved in the development of gastric erosions after curing H. pylori infection.     

幽门螺杆菌感染诱导胃黏膜上皮细胞凋亡及端粒酶逆转录酶表达

目的研究幽门螺杆菌（Hp）根除前后胃黏膜上皮细胞凋亡和端粒酶逆转录酶（hTERT）表达及其与bcl-2、c-myc蛋白表达的关系。方法采用脱氧核糖核酸末端转移酶介导的缺口末端标记（TUNEL）技术及免疫组化染色方法检测39例却Hp性患者根除治疗及21例却阴性患者对症治疗前后胃黏膜上皮细胞凋亡、hTERT、bcl-2、c—myc蛋白表达的变化。结果治疗前却阳性者胃黏膜上皮细胞凋亡指数为16．2％，显著高于却阴性者（P〈0．05）；却阳性者hTERT、c—myc蛋白表达显著高于却阴性者（53．8％比23．8％；53．8％比28．6％，P〈0．05）。邯根除者治疗后胃黏膜上皮细胞凋亡、hTERT及bcl-2、c—myc蛋白表达与根除前相比均显著下降（16．9％比9．0％；59．3％比22．2％；59．3％比25．9％；59．3％比14．8％，P〈0．01），且与却阴性对照组相比差异无统计学意义（P〈0．05）；而邯未根治组及对照组上述指标均无显著变化。治疗前bcl-2、c—myc蛋白与hTERT呈显著正相关，秩相关系数r分别为0．269、0．474（P〈0．05）。结论却感染诱导细胞凋亡及hTERT过度表达，使胃黏膜不稳定性增加。根除却可纠正细胞凋亡失调，使hTERT表达下降或消失，从而降低胃癌发生的可能性。bcl-2及c—myc蛋白对hTERT表达可能具有调控作用。     

Reflux esophagitis and hiatal hernia as concomitant abnormality in patients presenting with active duodenal or gastric ulcer: cross-sectional endoscopic study in consecutive patients

BACKGROUND: Follow-up studies have shown that patients with ulcer disease are at risk of developing reflux esophagitis (RE) after successful eradication of Heliobacter pylori. It is still not clear whether this is induced by eradication of H. pylori or whether RE is already present at the time the ulcer is diagnosed. A cross-sectional study was done in consecutive patients suffering from active ulcer disease in order to assess coincidental RE. METHODS: Patients with an active duodenal or gastric ulcer were included in the study. Concomitant RE and the presence of hiatal hernia (HH) were scored. Biopsy specimens were taken for detection of H. pylori. RESULTS: In 375 patients (77%), an active duodenal ulcer was the only abnormality. In 43 patients (8.8%), duodenal ulcer and concomitant RE were present and 69 patients (14.2%) had a duodenal ulcer with concomitant HH. Patients with a duodenal ulcer were significantly younger than patients with concomitant RE or HH. From 374 patients (76.8%) with a duodenal ulcer, biopsy specimens were available for the detection of H. pylori. The majority of duodenal ulcer patients were H. pylori-positive. H. pylori was significantly more often present in patients with an active duodenal ulcer than it was in duodenal ulcer patients suffering from concomitant RE (P=0.04). In 218 patients (76%), a gastric ulcer was the only abnormality. Fifteen patients (5.2%) also had RE and 54 patients (18.8%) had a concomitant HH. There was no difference in H. pylori status in these three groups of patients. CONCLUSIONS: Given the low prevalence of concomitant RE, it is concluded that this condition is likely to occur in a large percentage of patients suffering from H. pylori-positive ulcer disease after successful eradication therapy.     

幽门螺杆菌感染对胃上皮细胞凋亡的影响

本文采用切口末端标记方法前瞻性观察了16例正常胃牯膜标本和31例幽门螺杆菌阳性胃炎患者抗幽门螺杆菌治疗前后胃窦部上皮细胞凋亡的变化。结果表明,幽门螺杆菌感染者的凋亡指数(0.7044)明显高于正常对照者(P<0.005);幽门螺杆菌根除后凋亡指数由0.7624降至0.1159(P<0.005),而持续阳性者则无明显降低;凋亡指数与胃炎程度无关。提示幽门螺杆菌能促进胃上皮细胞凋亡,这可能是幽门螺杆菌引起胃癌和溃疡的重要机理。     

Effect of Helicobacter pylori eradication on bulbitis and duodenal gastric metaplasia

BACKGROUND/AIMS: Duodenal gastric metaplasia seems to be linked to infection by Helicobacter pylori, to the extent of acid secretion and to bulbitis. An investigation was made of the relationship between bulbitis and duodenal gastric metaplasia, or whether bulbitis can arise along with duodenal gastric metaplasia after Helicobacter pylori eradication in an average of six years. METHODOLOGY: We compared 22 patients with duodenal ulcers [male/female 16/6; (mean age+/-SD) 55+/-12 years] Helicobacter pylori-negative after eradication, with 23 Helicobacter pylori-positive patients free from active duodenal ulcers [male/female 17/6; (mean age+/-SD) 59+/-12 years]. RESULTS: The bulbitis score was found to be lower in the Helicobacter pylori-negative than in the Helicobacter pylori-positive group (p=0.02). The duodenal gastric metaplasia score in the Helicobacter pylori-negative was higher than in the Helicobacter pylori-positive group (p=0.001). We failed to find any relationship between the presence of bulbitis and duodenal gastric metaplasia. We found a non-significant inverse correlation between the presence of duodenal gastric metaplasia and chronic body gastritis (p=0.07). CONCLUSIONS: Bulbitis and duodenal gastric metaplasia may depend on different causal factors not related to Helicobacter pylori infection. The extension of duodenal gastric metaplasia with time following recovery from peptic ulcer disease may represent a mucosal protection factor against acid.     

Effects of Helicobacter pylori infection on gastric emptying rate in patients with non-ulcer dyspepsia

AIM: The pathogenesis of delayed gastric emptying in patients with non-ulcer dyspepsia (NUD) remains unclear. We aimed to examine whether gastric emptying rate in NUD patients was associated with Helicobacter pylori (H pylori) infection and whether it was affected by eradication of the infection. METHODS: Gastric emptying rate of a mixed solid-liquid meal was assessed by the paracetamol absorption method in NUD patients and asymptomatic controls (n=17). H pylori status was assessed by serology and biopsy urease test. H pylori-positive NUD patients (n=23) received 10-day triple eradication therapy. H pylori status was re-assessed by biopsy urease test four weeks later, and if eradication was confirmed, gastric emptying rate was re-evaluated. RESULTS: Thirty-three NUD patients and 17 controls were evaluated. NUD patients had significantly delayed gastric emptying compared with controls. The mean maximum plasma paracetamol concentration divided by body mass (Cmax/BM) was 0.173 and 0.224 mg/L.kg respectively (P=0.02), the mean area under plasma paracetamol concentration-time curve divided by body mass (AUC/BM) was 18.42 and 24.39 mg.min/L.kg respectively (P=0.01). Gastric emptying rate did not differ significantly between H pylori-positive and H pylori-negative NUD patients. The mean Cmax/BM was 0.172 and 0.177 mg/L.kg respectively (P=0.58), the mean AUC/BM was 18.43 and 18.38 mg.min/L.kg respectively (P=0.91). Among 14 NUD patients who were initially H pylori-positive, confirmed eradication of the infection did not significantly alter gastric emptying rate. The mean Cmax/BM was 0.171 and 0.160 mg/L.kg before and after Hp eradication, respectively (P=0.64), the mean AUC/BM was 17.41 and 18.02 mg.min/L.kg before and after eradication, respectively (P=0.93). CONCLUSION: Although gastric emptying is delayed in NUD patients compared with controls, gastric emptying rate is not associated with H pylori status nor it is affected by eradication of the infection.     

Does the depth of gastric ulceration influence a modified dual therapy with amoxicillin and lansoprazole for Helicobacter pylori-associated gastric ulcer?

PURPOSE: To clarify whether the depth of ulceration evaluated by endoscopic ultrasonography (EUS) influences a modified dual therapy with amoxicillin and lansoprazole for the treatment of Helicobacter pylori-positive patients with gastric ulcer. PATIENTS AND METHODS: Twenty-two consecutive cases of gastric ulcer (nine superficial ulcers and 13 deep ulcers) in H pylori-positive patients were studied. Ten of 22 patients received a two-week eradication therapy with amoxicillin 1500 mg/day, lansoprazole 30 mg/day and a new antiulcer agent with features in common with sucralfate, ecabet sodium, 2.0 g/day. They continued to receive the same doses of lansoprazole and ecabet sodium for the next six weeks. The other 12 patients received the same therapy except for those who underwent the four-week amoxicillin treatment. All patients underwent EUS both at the start of the study and eight weeks later. They then received ecabet sodium alone for the next six months as a maintenance therapy, followed by a six-month interval with no treatment. The final endoscopy was done one year after H pylori eradication therapy was completed to evaluate H pylori status and ulcer recurrence. RESULTS: The rates of endoscopic healing and H pylori eradication in the nine patients with superficial ulcer were 100%, irrespective of the period of amoxicillin treatment. In contrast, the rates of endoscopic evidence of healing and H pylori eradication in the 13 patients with deep ulcer were different for each period of amoxicillin treatment; that is, the rates of reduction in ulcer determined by echo and H pylori eradication in the four patients treated with the two-week amoxicillin course were significantly lower (P=0.03) than those in the nine patients treated with the four-week course. CONCLUSION: Ulcer depth is likely to influence the success of amoxicillin treatment for H pylori-positive patients with gastric ulcer.     

Regional differences in the recovery of gastric acid secretion after Helicobacter pylori eradication: evaluations with Congo red chromoendoscopy

BACKGROUND: Gastric-acid secretion is reduced in Helicobacter pylori-positive fundic atrophic gastritis, but it is restored by the eradication. However, changes in the distribution of acid-secreting mucosa after the eradication remain unknown. Congo red chromoendoscopy is capable of visualizing the acid-secreting fundic mucosa. OBJECTIVE: To evaluate the effect of H pylori eradication on the distribution of acid-secreting mucosa in the fundus by using Congo red chromoendoscopy. DESIGN: An assessment of the distribution of acid-secreting mucosa by the visualized images of Congo red chromoendoscopy and a histologic evaluation of biopsy specimens were performed before and 1 and 7 months after the eradication. The areas of the acid-secreting mucosa in the lesser and greater curvatures of the fundus were evaluated semiquantitatively. PATIENTS: Thirty-seven patients positive for H pylori and with fundic atrophic gastritis. RESULTS: The area of the acid-secreting mucosa increased in 27 cases (73%) by 1 month after eradication, and in 32 cases (86%) by 7 months. This expansion of the acid-secreting mucosa coincided with the improvement of inflammatory changes rather than with that of the mucosal atrophy and was more prominent on the greater curvature than on the lesser curvature. CONCLUSIONS: The acid-secreting mucosa in the fundus expanded in most cases with fundic atrophic gastritis after H pylori eradication, which could be responsible for the increase in acid secretion after the treatment. Regional differences in the recovery of local acid secretion may be associated with site-specific susceptibility to the development of gastric cancer after successful eradication.     

Perforin and granzyme B of cytotoxic T lymphocyte mediate apoptosis irrespective of Helicobacter pylori infection: possible act as a trigger of peptic ulcer formation

BACKGROUND/AIMS: The perforin/granzyme and Fas/Fas ligand pathways are two known major pathways of cytotoxic T lymphocyte-mediated apoptosis. We designed a clinical study to examine whether cytotoxic T lymphocyte-mediated apoptosis associated with peptic ulcer formation may occur via either or both of these two pathways. METHODOLOGY: Mucosal biopsy specimens were obtained endoscopically from the marginal zone of active stage gastric and duodenal ulcers in patients with or without Helicobacter pylori infection. RT-PCR, immunoblotting and immunohistochemistry were used to study the samples for the expression of apoptotic cells, perforin, granzyme B, Fas, Fas ligand and caspase 3. RESULTS: Apoptotic cells (Tunnel positive cells) appeared in the marginal zone of gastric and duodenal ulcers with and without H. pylori infection. Perforin/granzyme B and caspase 3 were expressed consistently, however Fas ligand was not. Furthermore, the immunohistochemical findings demonstrated apoptotic changes of target cells caused by perforin/granzyme B. CONCLUSIONS: These results suggest that the main pathway of cytotoxic T lymphocyte-mediated apoptosis in peptic ulcer formation is the perforin/granzyme pathway irrespective of H. pylori infection.     

What consideration should be given to Helicobacter pylori in treating nonsteroidal anti-inflammatory drug ulcers?

Although Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) both cause peptic ulcers, they do so by different mechanisms so any interaction is not necessarily harmful. H. pylori has been shown to enhance gastric mucosal prostaglandin synthesis, while NSAIDs suppress it Pragmatically, there is no compelling evidence in favour of H. pylori eradication in all patients who take NSAIDs. As a broad generalisation, in therapeutic studies of NSAID users, those who have no ulcer at trial entry are more prone to ulcer development if they are H. pylori-positive. By contrast, in those who have ulcers at baseline, H. pylori-positive individuals are less likely to develop ulcers, particularly if taking acid-suppressive therapy. Trials of H. pylori eradication therapy tend to replicate this dichotomy. In one study of patients starting NSAIDs for the first time, with no ulcer history and no baseline ulcer, use of bismuth-based eradication therapy was associated with a lower incidence of gastric ulcer at 2 months. Conversely, in a study of patients with endoscopically proven ulcers and/or troublesome dyspepsia, proton pump inhibitor based eradication treatment had no effect on outcome (of acid suppression) over 6 months. H. pylori eradication has been associated with significantly slower healing of gastric ulcers compared with patients who did not undergo eradication. However, the effect of H. pylori eradication on healing of NSAID-associated duodenal ulcers does not appear to be so dramatic, and limited evidence suggests that it may be possible to prevent H. pylori-associated duodenal ulcer by eradicating the infection. An evidence-based approach to treatment would suggest that NSAID users should undergo H. pylori eradication therapy if they have a duodenal ulcer, whether or not they continue NSAIDs. Because COX-2 inhibitors appear not to be ulcerogenic, management of H. pylori in patients taking these drugs can be based upon the same risk assessment as in patients not taking anti-arthritis drugs. H. pylori eradication should not be used universally or in high-risk gastric ulcer patients who require management with acid suppression.     

Antralization at the edge of proximal gastric ulcers： Does Helicobacterpyloriinfection play a role？

AIM: To determine the prevalence of antralization at the edge of proximal gastric ulcers, and the effect of H. pylori eradication on the mucosal appearances. METHODS: Biopsies were taken from the antrum, body and the ulcer edge of patients with benign proximal gastric ulcers before and one year after treatment. Gastric mucosa was classified as antral, transitional or body type. H. pylori positive patients received either triple therapy, or omeprazole. RESULTS: Patients with index ulcers in the incisura, body or fundus (n=116) were analyzed. Antral-type mucosa was more prevalent at the ulcer edge in H. pylori-positive patients than H. pylori-negative patients (93 % vs 60 %, OR=8.95, 95 %CI: 2.47-32.4, P=0.001). At one year, there was a significant reduction in the prevalence of antralization (from 93 % to 61 %, P=0.004) at the ulcer edge in patients with H. pylori being eradicated. However, there was no difference in the prevalence of antralization at the ulcer edge in those with persistent infection. CONCLUSION: H. pylori infection is associated with antralization at the edge of proximal gastric ulcers, which may be reversible in some patients after eradication of the infection.     

Apoptosis, proliferation and p53 gene expression of H. pylori associated gastric epithelial lesions

AIM:To study the relationship between Helicobacter pylori(H.pylori)and gaatric carcinoma and its possiblepathogenesis by H.pylori.METHODS:DNEL technique and immunohistochemicaltechnique were used to study the state of apoptosis,proliferation and p53 gone expression.A total of 100 gastricmucosal biopsy specimens,including 20 normal mucosa,30H.pylori-negative and 30 H.pylori-positive gastricprecancerous lesions along with 20 gastric carcinomas werestudied.RESULTS:There were several apoptotic cells in thesuperficial epithelium and a few proliferative cells within theneck of gestric glands,and no p53 protein expression innormal mucosa.In gestric carcinoma,there ware fewapoptotic cells,while there were a large number ofproliferative cells,and expression of p53 proteinsignificantly was increased.In the phase of metaplasia,theapoptotic index(Al,4.36%±1.95%),proliferative index(Pl,19.11%±6.79%)and positivity of p53 expression(46.7%)in H.pylori-positive group ware higher than thosein normal mucosa(P<0.01).Al in H.pylori-positive groupwas higher than that in H.pylori-negative group(3.81%±1.76%),Pl in H.pylori-positive group was higher than thatin H.pylori-negative group(12.23%±5.63%,P<0.01).Inthe phase of dysplasia,Al(2.31%±1.10%) in H.pylori-positive group was lower(3.05%±1.29%)than that in H.pylori-negative group,but Pl(33.89%±11.65%)wassignificantly higher(22.09±8018%,P<0.01).In phases ofmetaplasia,dysplasia and gastric cancer in the H.pylori-positive group,Als had an evidently greduall decreasingtrend(P<0.01),while Pls had an evidently gradualincreasing trend(P<0.05 or P<0.01),and there was alsoa trend of gradual increase in the expression of p53 gone.CONCLUSION:In the course of the formation of gastriccarcinoma,proliferation of gastric mucosa can be greatlyIncreased by H.pylori,and H.pylori can induce apoptosisin the phase of metaplasia,but in the phase of dysplesia H.pylorl can inhibit cellular apptosis.And H.pylori infectioncan strengthen the expression of mutated p53 gene.