Effect of Helicobacter pylori infection on gastric epithelial proliferation in progression from normal mucosa to gastriccarcinoma

ＥｆｅｃｔｏｆＨｅｌｉｃｏｂａｃｔｅｒｐｙｌｏｒｉｉｎｆｅｃｔｉｏｎｏｎｇａｓｔｒｉｃｅｐｉｔｈｅｌｉａｌｐｒｏｌｉｆｅｒａｔｉｏｎｉｎｐｒｏｇｒｅｓｓｉｏｎｆｒｏｍｎｏｒｍａｌｍｕｃｏｓａｔｏｇａｓｔｒｉｃｃａｒｃｉｎｏｍａＬＩＵＷｅｎＺｈｏｎ...     

Sustained increase in gastric antral epithelial cell proliferation despite cure of Helicobacter pylori infection

OBJECTIVE: Studies of the effect of Helicobacter pylori treatment on gastric mucosa proliferation have yielded inconsistent results. We compared gastric mucosa cell proliferation posttherapy and in uninfected controls. METHODS: Biopsies were obtained from patients with H. pylori infection before treatment and at intervals for up to 33 months. Epithelial cell proliferation was determined using Ki-67 immunostaining. The labeling index (LI) is the proportion of positively labeled cells with respect to the total number of cells. The proliferative index was calculated by multiplying the labeling index (LI) and the proliferation zone PZ (PZ = length of the area between the uppermost and lowest labeled cells). RESULTS: The study included 27 patients with H. pylori gastritis and 35 controls. Epithelial cell proliferation (LI) was greater with H. pylori infection than without in both the antrum and corpus (65+/-5 vs 91+/-8 in the antrum and 44+/-4 vs 72+/-8 in the corpus, for uninfected controls vs H. pylori gastritis, respectively) (p = 0.0001). In the antrum there was no significant decrease in epithelial cell proliferation after cure of the H. pylori infection despite follow-up for >2 yr (labeling index = 83+/-10). In contrast, epithelial cell proliferation decreased in the corpus and became similar to that in controls after 7-13 months. CONCLUSIONS: Patients with H. pylori infection have sustained high epithelial cell proliferation in the antrum compared to that in uninfected subjects. A continued increase in proliferation in the antrum after cure of H. pylori infection suggests continuing damage.     

Pathophysiology of gastric acid secretion in patients with chronic renal failure: influence of Helicobacter pylori infection

OBJECTIVES: The incidence of gastroduodenal diseases is high in patients with chronic renal failure (CRF). However, gastric acidity in CRF has been reported to range in level from low to high. Moreover, it remains unknown whether Helicobacter pylori infection influences gastric acidity in such patients. Thus, we aimed to clarify the pathophysiological perturbation in gastric acidity and to determine the influence of H. pylori infection in CRF. DESIGN: Case-control study. SETTING: A university hospital. SUBJECTS: Twenty-seven patients with CRF and 24 control patients, presenting with either gastrointestinal symptoms, positive faecal occult blood, or anaemia (haemoglobin <10 g dL(-1)). MEASURES: The patients underwent gastroduodenal endoscopy with simultaneous determination of H. pylori infection. Gastric ammonium concentration, serum pepsinogen I and II, and basal gastrin level were measured. Thereafter, gastric acid secretion was monitored by 24-h intragastric acidity measurement with calculation of pH-3 holding time (%) (hours showing pH>3/24 h). RESULTS: In the CRF group, pH-3 holding time of H. pylori (+) subgroup was significantly greater than that of H. pylori (-) subgroup (71.2 +/- 32.4% vs. 32.8 +/- 30.0%, mean +/- SD; P=0.03). Pepsinogen I/II ratio was inversely correlated with pH-3 holding time in the control and CRF groups. Gastric ammonium concentration in CRF/H. pylori (+) subgroup (14.1 +/- 9.2 mmol L(-1)) was significantly higher than in CRF/H. pylori (-) (2.5 +/- 2.7 mmol L(-1); P=0.002) and control/H. pylori (+) subgroups (6.1 +/- 4.2 mmol L(-1); P=0.01). Serum gastrin level was significantly higher in the CRF group than in the control group (297 +/-343 pg mL(-1) vs. 116 +/- 69 pg mL(-1); P=0.02) as a whole. However, there was no significant correlation between serum creatinine and gastrin levels in the CRF group. Gastrin level in CRF/H. pylori (+) subgroup was significantly higher than in CRF/H. pylori (-), control/H. pylori (+), and control/H. pylori (-) subgroups (423 +/-398 pg mL(-1) vs. 113 +/- 79, 124 +/- 78, and 96 +/-43 pg mL(-1), respectively; P=0.01-0.03). Significant positive correlations amongst pH-3 holding time, ammonium and gastrin concentrations were found in the CRF group, but not in the control group. CONCLUSIONS: CRF without H. pylori infection primarily shows a tendency for high gastric acidity, but without hypergastrinaemia. Persistent H. pylori infection in CRF leads to decreased acidity and, consequently, to fasting hypergastrinaemia via a feedback mechanism. The hypoacidity in CRF with H. pylori infection appears to result from neutralization of acid by ammonia as well as from gastric atrophy. Thus, H. pylori infection status critically determines perturbation in gastric acidity and fasting gastrin level in CRF.     

Gastric epithelial cell kinetics in the progression from normal mucosa to gastric carcinoma.

Increased epithelial cell proliferation is associated with an increased risk of adenocarcinoma and is associated with Helicobacter pylori infection. The aim of this study was to assess both gastric epithelial cell proliferation and the influence of H pylori infection on cell kinetics in the progression from normal mucosa to gastric carcinoma. One hundred and forty four subjects were assigned to study groups based on diagnosis and H pylori status: microscopically normal mucosa and H pylori negative (n = 28); chronic active gastritis and H pylori positive (n = 83); atrophic gastritis (n = 9); intestinal metaplasia (n = 19); gastric carcinoma (n = 12). Gastric antral epithelial cell proliferation was assessed using the in vitro bromodeoxyuridine immunohistochemical technique and expressed as the labelling index per cent (LI%). Subjects with chronic atrophic gastritis, intestinal metaplasia or gastric cancer have increased gastric epithelial cell proliferation compared with normal mucosa (LI% mean (SEM): 5.14 (0.6), 4.68 (0.3), 6.50 (0.5) v 3.08 (0.2), p < 0.001). This increase in gastric epithelial cell proliferation was not influenced by H pylori status. Gastritis associated with H pylori had an increased LI% compared with normal controls or subjects with H pylori negative gastritis (4.98 (0.2) v 3.08 (0.2), 3.83 (0.2), p < 0.01). H pylori infection although associated with an increased epithelial cell proliferation in subjects with chronic gastritis, does not influence the increased epithelial cell proliferation seen in subjects with precancerous lesions or gastric carcinoma. This is further evidence that H pylori may be an initiating step in gastric carcinogenesis.     

Gastric epithelial cell proliferation and ras oncogene p21 expression in first-degree relatives of gastric cancer patients: a case-control study

OBJECTIVES: Individuals with a family history of gastric cancer have an increased risk of developing such neoplasia. This study aimed to assess epithelial cell proliferation and ras oncogene mutation in such individuals. METHODS: Twenty dyspeptic, first-degree relatives of patients with gastric cancer and 20 matched controls were enrolled. Endoscopy with biopsies was performed in all cases. Gastric specimens were used to look for Helicobacter pylori infection and to assess both epithelial cell proliferation and ras oncogene expression by immunohistochemistry. RESULTS: Cell proliferation values were not significantly different between the patient and control groups (18.1 +/- 7.1 versus 18.9 +/- 7.4; P = 0.7). Overall, ras mutation was detected in five out of 40 cases, and its distribution was similar between patients and controls (20 versus 10%; P = 0.9), as well as between H. pylori-positive and negative patients (22 versus 9%; P = 0.2). Cell proliferation values tended to be higher in cases with ras mutation than in those without (25.2 +/- 9.4 versus 16.8 +/- 5.8; P = 0.08). Cell proliferation values were significantly higher in H. pylori-positive cases compared with uninfected cases, in both patient (24.7 +/- 4.7 versus 12.5 +/- 2.4; P = 0.0003) and control (25.9 +/- 4.8 versus 13.3 +/- 2.8; P = 0.0003) groups. CONCLUSIONS: Both gastric cell proliferation values and ras mutation prevalence did not differ between first-degree relatives of gastric cancer patients and controls. H. pylori infection similarly increased the proliferation index of gastric mucosa in both groups.     

Effect of Helicobacter pylori infection on Bax protein expression in patients with gastric precancerous lesions

AIM: To investigate the effect of Helicobacter pylori (H pylori) infection on Bax protein expression, and explore the role of H pylori in gastric carcinogenesis. METHODS: H pylori was assessed by rapid urease test and Warthin-Starry method, and expression of Bax protein was examined immunohistochemically in 72 patients with pre-malignant lesions. RESULTS: Bax protein was differently expressed in intestinal metaplasia and gastric dysplasia, and showed 63.99% positivity. The positivity of Bax protein expression in Hpylori-positive gastric precancerous lesions (72.3%) was significantly higher than that in H pylori-negative gastric precancerous lesions (48.0%, X~2=4.191, P<0.05). H pylori infection was well correlated with the expression of Bax protein in gastric precancerous lesions (r=0.978, P<0.01). After eradication of H pylori, the positivity of Bax protein expression significantly decreased in H pylort-positive gastric precancerous lesions (X~2=5.506, P<0.05). In the persisting H pylori-infected patients, the positivity of Bax protein expression was not changed. CONCLUSION: H pylori infection may be involved in the upregulation of Bax gene, which might be one of the mechanisms of H pylori infection-induced gastric epithelial cell apoptosis. H pylori might act as a tumor promoter in the genesis of gastric carcinoma and eradication of H pylori could inhibit gastric carcinogenesis.     

幽门螺杆菌相关胃溃疡的细胞增殖与凋亡研究

目的观察Ｈｐ感染对胃溃疡（ＧＵ）患者胃粘膜上皮细胞增殖与凋亡的影响,进而对溃疡发生机制进行探讨．方法标本取自内镜下胃粘膜活检,细胞凋亡检测采用Ｔｕｎｅｌ方法,细胞增殖检测采用免疫组化ＬＳＡＢ方法测定增殖细胞核抗原（ＰＣＮＡ）．结果ＧＵＨｐ＋患者细胞凋亡指数（ＡＩ）明显高于Ｈｐ－患者（Ｐ＜００５）,但比较两者的增殖细胞指数（ＰＣＮＡＬＩ）,无显著性差异（Ｐ＞００５）;慢性浅表性胃炎Ｈｐ＋患者ＡＩ,ＰＣＮＡＬＩ明显高于Ｈｐ－患者（Ｐ＜００５）,ＧＵＨｐ＋患者的ＡＩ／ＰＣＮＡＬＩ比值为１５４１,明显高于其他各组（Ｐ＜００５）．结论Ｈｐ感染能诱导ＧＵ患者胃粘膜上皮细胞凋亡增加,出现细胞凋亡与细胞增殖平衡失调,促进溃疡形成     

Effect of Helicobacter pylori eradication on anti-thrombotic dose aspirin-induced gastroduodenal mucosal injury

BACKGROUND: Helicobacter pylori infection and non-steroidal anti-inflammatory drugs are two major causes of gastric injury but the effect of H. pylori eradication on the development of aspirin-induced gastric mucosal injury is unclear. The aim of the present study was to investigate the effect of Helicobacter pylori eradication on gastroduodenal mucosal injury induced by antithrombotic doses of aspirin. METHODS: Patients who had been planned to start on medium-dose aspirin (300 mg) for any kind of indication were included in the study. All subjects underwent upper gastrointestinal endoscopy for determination of H. pylori status and Lanza score. The H. pylori-positive patients were randomized to receive either aspirin + eradication (omeprazole 20 mg b.i.d. and amoxicillin 500 mg q.i.d. for 2 weeks) or aspirin + placebo eradication. Endoscopic reassessment was done 4 months after the onset of aspirin or when symptoms developed. RESULTS: Thirty-two patients (placebo group n = 16, H. pylori-eradicated group n = 16) completed the study and Lanza scores of both groups were similar before treatment. Lanza scores significantly increased in the placebo group (0.69 +/- 0.87 vs 2.25 +/- 1.3, P < 0.0001) and did not change in the H. pylori-eradicated group after aspirin treatment (0.43 +/- 0.72 vs 0.75 +/- 0.93, P > 0.05). CONCLUSION: Helicobacter pylori eradication may prevent medium-dose aspirin-induced gastroduodenal mucosal injury.     

Effect of drug treatment on hyperplastic gastric polyps infected with Helicobacter pylori： A randomized, controlled trial

AIM: To study the effects of drug treatment on hyperplastic gastric polyps infected with Helicobacter pylori (H pylori). METHODS: Forty-eight patients with hyperplastic gastric polyps (3-10 mm in diameter) infected with H pylori were randomly assigned to a treatment group (n = 24) which received proton-pump inhibitor (omeprazole or lansoprazole), clarithromycin, bismuth citrate and tinidazole, and a control group (n = 24) which received protective agent of gastric mucosa (tepretone). Patients underwent endoscopy and H pylori examination regularly before enrollment and 1-12 mo after treatment. RESULTS: Twenty-two patients in the treatment group and 21 in the control group completed the entire test protocol. In the treatment group, polyps disappeared 1-12 mo (average, 6.5+/-1.1 mo) after the treatment in 15 of 22 patients (68.2%) and H pylori infection was eradicated in 19 of the 22 patients (86.4%). However, 12 months after the study, no change in polyps or H pylori status was seen in any controls ((b)P<0.01). CONCLUSION: Most hyperplastic gastric polyps disappear after eradication of H pylori.     

Gastric cellular turnover and the development of atrophy after 31 years of follow-up: a case-control study

OBJECTIVE: Why only some patients colonized with Helicobacter pylori (H. pylori) develop atrophy, a preneoplastic change, is not known. Because gastric mucosal mass is dependent upon a balance between epithelial proliferation and turnover, we hypothesized that atrophy may develop due to increased apoptosis relative to proliferation. METHODS: Gastric epithelial apoptosis was measured by terminal deoxyuridine nucleotide nick end labeling (TUNEL) assay and proliferation by Ki-67 immunohistochemistry in gastric corpus biopsies in a unique cohort of patients followed for 31 yr (1952-1983). Sixteen patients who developed atrophy over this time were selected (cases), with two matched controls, who did not develop atrophy, for each. Apoptosis and proliferation were measured in the corpus biopsies taken in 1952. RESULTS: Cases (N = 16) and controls (N = 32) were well matched for age, sex, initial histology, and severity of H. pylori infection. In the initial (1952) biopsies, 4.3 +/- 1.7 cells (mean +/- SEM) per gland were Ki-67-positive in the cases, compared with 2.1 +/- 0.4 in controls (p = 0.48). 9.2 +/- 2.3 cells per gland were terminal deoxyuridine nucleotide nick end labeling-positive in cases, compared with 6.3 +/- 0.8 in controls (p = 0.29). Proliferation to apoptosis ratios were similar in both groups (cases, 0.38 +/- 0.16; controls 0.39 +/- 0.08, p = 0.37). CONCLUSIONS: Patients who later developed atrophy, initially had mildly (but not statistically significant) increased gastric epithelial cell proliferation and apoptosis, compared with those patients who did not develop atrophy, suggesting increased cellular turnover in the atrophy group. However, in these patients with gastritis, the ratio of apoptosis to proliferation was not a determinant of risk for development of atrophy decades later.     

Antralization of gastric incisura is topographically associated with increased gastric epithelial apoptosis and proliferation, but not with CagA seropositivity

BACKGROUND AND AIMS: Helicobacter pylori infection is linked with increased antralization at the gastric incisura. The present study aimed to determine if antralization is associated with altered gastric epithelial apoptosis and proliferation and with seropositivity of the cytotoxin-associated gene product A (CagA) of H. pylori. METHODS: Gastric biopsies taken from the antrum, incisura, body and fundus of 75 patients (34 male, 41 female; mean age 59.5 years) were used for diagnosis of H. pylori infection and assessments of histological changes. Apoptosis and Ki-67 expression in epithelial cells were determined for the antral, incisura and body biopsies by immunohistochemistry. Serum samples were tested by enzyme-linked immunosorbent assays for anti-H. pylori and anti-CagA IgG antibodies. RESULTS: Apoptotic index (AI) and Ki-67 proliferation index (PI) were greater in the presence (vs absence) of H. pylori infection at the antrum, incisura and body (all P < 0.001), and topographically associated with chronic gastritis and gastric atrophy/intestinal metaplasia at the antrum and incisura (all P < 0.001). Moreover, AI and PI were greater in the presence (vs absence) of antralization at the incisura (20.2 +/- 0.9 vs 11.4 +/- 0.1.1 and 48.9 +/- 2.5 vs 29.9 +/- 2.5, both P < 0.001). CagA seroprevalence was 41% in the 39 infected patients. CagA seropositivity was associated with gastric atrophy/intestinal metaplasia at the antrum (chi(2) = 4.67, P = 0.03) and incisura (chi(2) = 4.88, P = 0.03), but not associated with gastric epithelial apoptosis and Ki-67 expression, nor with antralization at the incisura. CONCLUSIONS: Antralization of gastric incisura is topographically associated with increased gastric epithelial apoptosis and proliferation, but not with CagA seropositivity.     

Topographic association of gastric epithelial expression of Ki-67, Bax,and Bcl-2 with antralization in the gastric incisura,body, and fundus

OBJECTIVES: Helicobacter pylori (H. pylon) infection seems to induce antralization (ie., gastric mucosal transformation from transitional or body type to antral type), which is strongly associated with gastric atrophy and intestinal metaplasia. The aim of this study was to determine the topographic associations of Ki-67 (a protein expressed in proliferative cells), Bax (a pro-apoptotic protein), and Bcl-2 (an antiapoptotic protein) expression with antralization. METHODS: In each of 104 patients, eight biopsy specimens were taken from the gastric antrum, incisura, body, and fundus for the determination of H. pylori infection, histological changes, and epithelial expression of Ki-67, Bax, and Bcl-2. A labeling index (LI), i.e., the rate of positive cells over total cells counted, was used for Ki-67 and Bax expression. Bcl-2 overexpression was considered to be present if the rate of Bcl-2 positive cells over total cells counted was > or = 5%. RESULTS: H. pylori infection was present at the gastric antrum, incisura, body, and fundus in 50, 48, 51, and 49 patients, respectively. Ki-67 LI was greater in the presence vs absence) of H. pylori infection at the antrum (51 vs 40), incisura (47 vs 36), body (43 vs 30), and fundus (41 vs 31) (all p < 0.001). At the incisura, Ki-67 LI was greater (47 vs 32, p < 0.001), Bax LI was lower (22 vs 30, p < 0.05), and prevalence of Bcl-2 overexpression was higher (44% vs 18%, p < 0.001) in the presence (vs absence) of antralization. Compared with normal mucosa, gastric atrophy/intestinal metaplasia were associated with an increased Ki-67 LI and decreased Bax LI at the antrum (49 vs 32 and 15 vs 23, respectively), incisura (47 vs 32 and 15 vs 26, respectively) (all p < 0.001). Bcl-2 overexpression was more frequent in gastric atrophy/intestinal metaplasia at the antrum (56% vs 11%, p < 0.001) and incisura (63% vs 19%, p < 0.001) compared with normal mucosa. CONCLUSIONS: Antralization at the incisura is topographically associated with increased cell proliferation, reduced Bax expression, and Bcl-2 overexpression, which implies that antralization may be an important histological marker for future cancer risk.     

Gastric Epithelial Cell Proliferation in Patients with Liver Cirrhosis

An increased risk for gastric cancer in patients with liver cirrhosis has recently been reported. This study was performed in order to determine gastric epithelial cell proliferation in cirrhotic patients and to evaluate the role of congestive gastropathy (CG) and Helicobacter pylori infection in this process. Thirty-six cirrhotic patients and 18 controls were enrolled in the study. All patients underwent endoscopy and three biopsies were performed in the antrum and three in the gastric body. The presence of H. pylori infection was assessed by a rapid urease test and histology. The antral biopsies were used for gastric cell proliferation assessment by an immunohistochemical analysis (Ki-67). There was no significant difference in epithelial cell proliferation between cirrhotics and controls. Gastric proliferation values were higher in patients with H. pylori infection compared with uninfected patients, both in cirrhotic (P = 0.003) and in control groups (P = 0.06). Among the cirrhotic group, we found a progressive increase in gastric cell proliferation values related to the degree of CG, the highest values being observed in cirrhotic patients with severe CG. Moreover, cirrhotics with both severe CG and H. pylori infection had the highest proliferation values when compared with all other subgroups. In conclusion, this study found that: (1) CG significantly affects epithelial cell proliferation in gastric mucosa in cirrhotic patients, (2) H. pylori infection plays a similar role in gastric cell proliferation in both cirrhotic and non-cirrhotic patients, and (3) CG and H. pylori could act synergistically in this process.     

Delay in gastric emptying in patients with chronic renal failure

BACKGROUND: Gastrointestinal (GI) symptoms are common in patients with chronic renal failure (CRF). Delayed gastric emptying might be a possible pathophysiological mechanism. The aims of this study were to evaluate gastric emptying in patients with CRF and to correlate the findings with GI symptoms and evaluate the impact of Helicobacter pylori infection in CRF patients on gastric emptying. METHODS: Thirty-nine patients with CRF (17 F, 22 M) were compared with 131 healthy subjects (74 F, 57 M). A standardized breakfast was given with 20 spherical, radiopaque markers (ROMs). The emptying was followed by fluoroscopy after 4, 5 and 6 h. Gastric emptying was assessed by calculating the individual mean percentual gastric retention of markers, 4 to 6 h after the meal. The perceived severity of GI symptoms was assessed with a validated questionnaire. Because of gender differences in gastric emptying, men and women were compared separately and a percentile of 95 was chosen as the upper reference value. H. pylori infection was assessed using a serological method. RESULTS: Delayed gastric emptying was found in 14 out of 39 (36%) of the CRF patients. There was no relationship between delayed gastric emptying and age, GI symptoms, H. pylori infection or underlying renal disease. However, a higher proportion of patients in peritoneal dialysis demonstrated delayed gastric emptying compared with predialytic patients (6 of 9 versus 2 of 13, P = 0.026). Men with CRF had a higher gastric retention compared with healthy men (16.6 (0-63.3)% versus 0 (0-2.1)%, P < 0.0001), and 10 men with CRF had delayed gastric emptying (P < 0.0001). There was no significant difference in mean gastric retention between women with CRF and healthy women (13.3 (0-55.4)% versus 10.8 (0-30.0)%, P = 0.93), but 4 women with CRF had delayed gastric emptying (P = 0.02). Eighteen of the CRF patients had GI symptoms (6 F, 12 M) and 21 were asymptomatic (11 F, 10 M). There was no difference in mean gastric retention in patients with CRF with and without GI symptoms (M: 13.3 (0-55.0)% versus 47.5 (5.0-65.0)%, P = 0.51, F: 16.6 (0-63.3)% versus 13.3 (0-59.2)%, P = 0.96). Gastric emptying in CRF patients with and without H. pylori infection showed no difference. CONCLUSIONS: Delayed gastric emptying is common in patients with chronic renal failure, particularly in men. The delay was not associated with the presence of GI symptoms, underlying renal disease or H. pylori infection. However, the dialytic status might have an impact on gastric emptying in patients with CRF.     

Overexpression of cyclin E in Mongolian gerbil With Helicobacter pylori—induced gastric precancerosis

AIM: To explore dysregulation of cyclin E in malignancies,and to further investigate the role of cyclin E in Helicobacterpylori ( H. pylori)-induced gastric precancerosis.METHODS: Four-week-old specific pathogen-free maleMongolian gerbils were employed in the study. 0.5 mL 1 ×108 cfu@ L- 1 suspension of H. pylori NTCC11637 in Brucellabroth was inoculated orally into each of 20 Mongolian gerbils, and a further 20 gerbils were inoculated with Brucella brothas controls. 10 of the infected gerbils and 10 of the non-infected control gerbils were sacrificed at 25, 45 wk afterinfection. The expression of cyclin E was analyzed by RT-PCR and immunohistochemical studies with monoclonalantibody to cyclin E in Mongolian gerbil of H. pylori-induced gastric precancerosis.RESULTS: H. pylori was constantly detected in all infectedanimals throughout the study. At 25 wk after infection of H.pylori, ulcers were observed in the antral and body ofstomach ( n = 6). Histological examination showed that allanimals developed severe inflammation and multifocallymphoid follicles appeared in the lamina propria andsubmucosa of gastric antrum. At 45 wk after infection of H.pylori, severe atrophic gastritis (n = 10), intestinalmetaplasia (n = 8) and dysplasia (n = 6) could beobserved. Cyclin E mRNA levels were significantly more at25 wk after infection of H. pylori (1.27±0.26), and at45 wkafter infection of H. pylori (1.82 ± 0.39 ) than control-animals (0.59 ± 0.20, P＜ 0.01) ; cyclin E mRNA levels wereevaluated by 2.2-fold at 25 wk ( P ＜ 0.01 ) and 3. 1-fold at 45wk ( P ＜ 0.01 ) precancarosis induced by H. pylori, whencompared with control gastric epithelium of Mongoliangerbil. Immunohistochemical staining revealed exclusivenuclear staining of cyclin E. Furthermore, there wes asequential increase in cyclin E positive cells from normalepithelium to precancerosis.CONCLUSION: Overexpression of cyclin E occurs relativelyearly in gastric tumorigenesis in this model.     

Distribution of cagG gene in Helicobacter pylori isolates from Chinese patients with different gastroduodenal diseases and its clinical and pathological significance

AIM: To determine the distribution of cagG gene of Helicobacter pylori(Hpylori) isolates cultured from patients with various digestive diseases and its relationship with gastroduodenal diseases.METHODS: cagG was amplified by polymerase chain reaction in 145 H pylori isolates cultured from patients with chronic gastritis (n=72), duodenal ulcer (n=48), gastric ulcer (n=17), or gastric and duodenal ulcer (n=8), and the relationship between cagGstatus and the grade of gastric mucosal inflammation was determined.RESULTS: cagG was present in 91.7% of the 145 H pylori isolates, with the rates were 90.3%, 93.8%, 88.2% and 100.0%, respectively, in those from patients with chronic gastritis, duodenal ulcer, gastric ulcer, and gastric and duodenal ulcer. There was no significant difference among the four groups (P＞0.05). The average grade of gastric mucosal inflammation in the antrum and corpus was 1.819±0.325and 1.768±0.312, respectively in cagG positive patients,whereas the average inflammation grade was 1.649±0.297,1.598±0.278 respectively in cagG negative cases (P＞0.05).CONCLUSION: cagG gene of H pylori was quite conservative,and most H pylori strains in Chinese patients were cagG positive.cagG status was not related to clinical outcome or the degree of gastric mucosal inflammation. Therefore, cagG can notbe used as a single marker for discrimination of H pylori strains with respect to a specific digestive disease.     

Expression of TFF2 and Helicobacter pylori infection in carcinogenesis of gastric mucosa

AIM: To investigate the expression of TFF2 and Helicobacter pyloriinfection in carcinogenesis of gastric mucosa.METHODS: The expression of TFF2 was immunohistochemically analyzed in paraffin-embedded samples from 119 patients with endoscopic biopsy and subtotal gastrectomy specimens of gastric mucosal lesions, including 16 cases of chronic superficial gastritis (CSG), 20 chronic atrophic gastritis (CAG),35 intestinal metaplasia (IN), 23 gastric epithelial dysplasia (GED) and 25 gastric carcinoma (CA), and Helicobacter pylori infection was detected by Warthin-Starry staining.RESULTS: 1:TFF2 was located in the cytoplasm of gastrk mucous neck cell. The expression of TFF2 was 100 %,100 %, 0, 56.5 % and 0 in CSGs, CAGs, INs, GEDs and CAs, respectively. 2: The value of TFF2 positive cell density in CSG with Helicobacter pyloriinfection was higher than that without Helicobacter pyloriinfection. (52.89±7.27vs46.49±13.04, P＞0.05); But the value of TFF2 positive cell density in CAG and GED with Helicobacter pyloriinfection was significantly lower than that without Helicobacter pylori infection (18.17±4.09 vs 37.93±13.80, P＜0.01 and 14.44±9.32 vs 24.84±10.22, P＜0.05).CONCLUSION: Increase of TFF2 expression in CSG is perhaps associated with the protective mechanism after gastric mucosal injury. Decrease of TFF2 expression in CAG possibly attributes to the decrease in the number of gastric gland cell expressing TFF2. Re-expression of TFF2 in gastric epithelial dysplasia implies that TFF2 possibly contributes to the initiation of gastric carcinoma. The effect of Helicobacter pylori on the expression of TFF2 depends on the status of gastric mucosa.     

Helicobacter pylori enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in human gastric epithelial cells

AIM: To investigate the relations between tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Helicobacter pylori (H pylori) infection in apoptosis of gastric epithelial cells and to assess the expression of TRAIL on the surface of infiltrating T-cells in H pylori-infected gastric mucosa. METHODS: Human gastric epithelial cell lines and primary gastric epithelial cells were co-cultured with H pylori in vitro, then recombinant TRAIL proteins were added to the culture. Apoptosis of gastric epithelial cells was determined by a specific ELISA for cell death. Infiltrating lymphocytes were isolated from H pylori-infected gastric mucosa, and expression of TRAIL in T cells was analyzed by flow cytometry. RESULTS: The apoptosis of gastric epithelial cell lines and primary human gastric epithelial cells was mildly increased by interaction with either TRAIL or H pylori alone. Interestingly, the apoptotic indices were markedly elevated when gastric epithelial cells were incubated with both TRAIL and H pylori (Control vs TRAIL and H pylori: 0.51+/-0.06 vs 2.29+/-0.27, P = 0.018). A soluble TRAIL receptor (DR4-Fc) could specifically block the TRAIL-mediated apoptosis. Further studies demonstrated that infiltrating T-cells in gastric mucosa expressed TRAIL on their surfaces, and the induction of TRAIL sensitivity by H pylori was dependent upon direct cell contact of viable bacteria, but not CagA and VacA of H pylori. CONCLUSION: H pylori can sensitize human gastric epithelial cells and enhance susceptibility to TRAIL-mediated apoptosis. Modulation of host cell sensitivity to apoptosis by bacterial interaction adds a new dimension to the immunopathogenesis of H pylori infection.