Effect of Helicobacter pylori infection on cyclooxygenase‐2 expression in gastric antral mucosa

OBJECTIVE: Helicobacter pylori infection is a major etiological cause of chronic gastritis. Inducible cyclooxygenase (COX‐2) is an important regulator of mucosal inflammation. Recent studies indicate that expression of COX‐2 may contribute to gastro­intestinal carcinogenesis. The aim of this study was to investigate the effects of H. pylori infection and eradication therapy on COX‐2 expression in gastric antral mucosa. METHODS: Antral biopsies were taken from 46 H. pylori‐infected patients, who also had chronic gastritis, both before and after anti‐H. pylori treatment. The COX‐2 protein was stained by using immunohistochemical methods and COX‐2 expression was quantified as the percentage of epithelial cells expressing COX‐2. Gastritis and H. pylori infection status were graded according to the Sydney system. RESULTS: Cyclooxygenase‐2 expression was detected in the cytoplasm of gastric antral epithelial cells both before and after the eradication of H. pylori. Cyclooxygenase‐2 expression in mucosa with H. pylori infection was compared with the corresponding mucosa after successful H. pylori eradication (20.1 ± 13.1%vs 13.8 ± 5.9%; P < 0.05). At the same time, COX‐2 expression in H. pylori‐infected mucosa was com­pared with the normal controls (18.0 ± 14.1%vs 12.3 ± 4.6%, P < 0.05). Expression of COX‐2 was correlated with the degree of chronic inflammation (r= 0.78, P < 0.05). CONCLUSIONS: Our results showed that H. pylori infection leads to gastric mucosal overexpression of COX‐2 protein, suggesting that the enzyme is involved in H. pylori‐related gastric pathology in humans.     

Helicobacter pylori-Associated Gastritis Evolution of Histologic Changes over 10 Years

Background: Helicobacter pylori seems to be the commonest cause of chronic gastritis, but the natural course of H. pylori-associated gastritis is largely obscure. Methods: We present a histologic follow-up of 39 patients with H. pylori-positive gastritis. Gastroscopies with stepwise biopsies were performed in all the patients at an interval of 10 years. Results: Of the patients 87% (34/39) had a persistent infection and showed a significant decrease in the grades of antral gastritis, eosinophilic granulocytes, corpus eosinophilic granulocytes, and foveolar hyperplasia and a significant increase in the grade of corpus neutrophilic granulocytes. The quantities of H. pylori as estimated histologically did not change significantly during the follow-up period inpatients with a persistent infection. In the five other patients (13%) the H. pylori infection had apparently disappeared spontaneously, and this was accompanied by decreases in the amount of inflammatory cells in the gastric mucosa. Conclusions: H. pylori infection in the gastric mucosa is chronic and may be associated with both regressive and progressive histologic changes. Spontaneous healing of H. pylori infection is possible and is associated with partial resolution of the inflammatory changes in the gastric mucosa.     

Correlations among Helicobacter pylori infection and the expression of cyclooxygenase‐2 and vascular endothelial growth factor in gastric mucosa with intestinal metaplasia or dysplasia

Background and Aims: To examine the rate of Helicobacter pylori infection and the expression of cyclooxygenase‐2 (COX‐2) and vascular endothelial growth factor (VEGF) in gastric mucosa with intestinal metaplasia or dysplasia, and explore their correlations in precancerous gastric lesions. Methods: A total of 172 patients were included in the study. H. pylori infection was evaluated by hematoxylin–eosin and modified Giemsa staining. The expression of COX‐2 and VEGF proteins was detected by immunohistochemistry. Results: The rates of H. pylori infection in gastric mucosal dysplasia (DYS), intestinal metaplasia in gastric mucosa (IM), chronic atrophic gastritis (CAG) and chronic superficial gastritis (CSG) patients were significant differences (P = 0.001). The average optical density (AOD) values of COX‐2 staining in CSG, CAG, IM and DYS patients were 13.81 ± 5.53, 45.28 ± 21.44, 73.67 ± 26.02 and 91.23 ± 45.11, respectively, with significant differences among CSG, CAG and IM patients (P = 0.037, 0.001 and 0.047 for CSG vs CAG, CSG vs IM and CAG vs IM, respectively). The expression level of VEGF in DYS patients was significantly higher than those in other patients (P = 0.001, 0.001 and 0.001 for DYS vs CSG, DYS vs CAG and DYS vs IM, respectively). The expression levels of COX‐2 in H. pylori‐positive IM, CAG and DYS patients were significantly higher than those in H. pylori‐negative counterparts (P = 0.043, 0.009, 0.001, respectively). Additionally, the expression level of COX‐2 was positively correlated with that of VEGF with the aggravation of gastric mucosal lesions (r = 0.640, P = 0.006). Conclusion: H. pylori infection might be able to induce the expression of COX‐2 in precancerous gastric lesions, which in turn upregulates the expression of VEGF.     

MGMT and MLH1 methylation in Helicobacter pylori-infected children and adults

AIM:To evaluate the association between Helicobacter pylori(H.pylori) infection and MLH1 and MGMT methylation and its relationship with microsatellite instability(MSI).METHODS:The methylation status of the MLH1 and MGMT promoter region was analysed by methylation specific methylation-polymerase chain reaction(MSPPCR) in gastric biopsy samples from uninfected or H.pylori-infected children(n = 50),from adults with chronic gastritis(n = 97) and from adults with gastric cancer(n = 92).MLH1 and MGMT mRNA expression were measured by real-time PCR and normalised to a constitutive gene(β actin).MSI analysis was performed by screening MSI markers at 4 loci(Bat-25,Bat-26,D17S250 and D2S123) with PCR;PCR products were analysed by single strand conformation polymorphism followed by silver staining.Statistical analyses were performed with either the χ 2 test with Yates continuity correction or Fisher’s exact test,and statistical significance for expression analysis was assessed using an unpaired Student’s t-test.RESULTS:Methylation was not detected in the promoter regions of MLH1 and MGMT in gastric biopsy samples from children,regardless of H.pylori infection status.The MGMT promoter was methylated in 51% of chronic gastritis adult patients and was associated with H.pylori infection(P < 0.05);this region was methylated in 66% of gastric cancer patients,and the difference in the percentage of methylated samples between these patients and those from H.pylori-infected chronic gastritis patients was statistically significant(P < 0.05).MLH1 methylation frequencies among H.pylori-infected and non-infected chronic gastritis adult patients were 13% and 7%,respectively.We observed methylation of the MLH1 promoter(39%) and increased MSI levels(68%) in samples from gastric cancer patients in comparison to samples from H.pylori-infected adult chronic gastritis patients(P < 0.001 and P < 0.01,respectively).The frequency of promoter methylation for both genes was higher in gastric cancer samples than in H.pylori-positiv     

Duodenogastric Reflux and Helicobacter pylori Infection Synergistically Increase Gastric Mucosal Cell Proliferative Activity in Mongolian Gerbils

Background: Helicobacter pylori and duodenogastric reflux (DGR) are both recognized as aetiological factors in chronic gastritis and gastric carcinogenesis. In this study, a Mongolian gerbil (MG) model was used to investigate the histopathological changes in the gastric mucosa resulting from DGR and/or H. pylori infection. Methods: One-hundred-and-eleven 7-week-old, specific-pathogen-free, male MGs were divided into four groups: normal controls, gerbils with surgically induced DGR, and H. pylori-infected gerbils with and without DGR. Gerbils were killed 4, 12 and 26 weeks after DGR surgery, their stomachs removed and sections prepared. Sections were fixed immediately in 20% phosphate-buffered formalin and subjected to haematoxylin and eosin staining, Alcian blue at pH 2.5/periodic acid-Schiff staining, and immunostaining for smooth muscle cells, H. pylori and 5′-bromo-2′-deoxyuridine (BrdU). Results: The gastric mucosa of H. pylori-infected gerbils showed chronic active gastritis irrespective of DGR throughout the experimental period. The gastric mucosa of H. pylori-infected gerbils with DGR demonstrated higher BrdU labelling than in the other groups. Conclusions: In MGs, DGR and H. pylori infection synergistically increased gastric mucosal cell proliferative activity. DGR and H. pylori infection may be involved synergistically in gastric carcinogenesis by increasing cell proliferative activity.     

Peroxiredoxin I protects gastric mucosa from oxidative injury induced by H. pylori infection

Background and Aim: Helicobacter pylori (H. pylori) infection enhances the production of reactive oxygen species and peroxynitrite, thereby resulting in oxidative tissue damage. In this study, we examined the role of peroxiredoxin I (Prx I), a stress‐induced antioxidant enzyme, in protecting gastric mucosa from H. pylori‐induced gastric mucosal injury. Methods: Wild type (Prx I^+/+) and Prx I‐deficient type (Prx I^–/–) mice were maintained for 2 to 12 months with or without infection of H. pylori, Sydney strain‐1. Gastric mucosal expression of Prx I was assessed by immunoblot analysis and immunohistochemistry. The degree of gastritis was evaluated by the updated Sydney system and by mucosal levels of inflammatory cytokines (MIP‐2, IL‐1β, and TNF‐α). Oxidative DNA injury and apoptosis were analyzed by mucosal level of 8‐hydroxy‐2′‐deoxyguanosine, and the number of apoptotic cells stained with a single‐stranded DNA antibody, respectively. Results: H. pylori infection upregulated gastric mucosal Prx I expression in the Prx I^+/+ but not the Prx I^–/– mice. H. pylori infection also induced more severe gastritis and a more prominent increase in MIP level, more marked oxidative DNA injury, and apoptosis in the Prx I^–/– than the Prx I^+/+ mice. In the absence of H. pylori infection, no changes were demonstrated in gastric mucosa in either the Prx I^+/+ or the Prx I^?/? mice. Conclusion: These data suggest that H. pylori infection upregulates gastric mucosal Prx I expression, and further, that Prx I plays an important role in gastric mucosal protection against oxidative injury induced by H. pylori infection.     

T cells increase with gastric mucosal interleukin (IL)-7, IL-1, and Helicobacter pylori urease specific immunoglobulin levels via CCR2 upregulation in Helicobacter pylori gastritis

Background and Aims: The purpose of this study was to investigate possible factors that could impact on γδ T cell accumulation in the gastric mucosa. Method: Subjects were 22 Helicobacter pylori (H. pylori)‐free and 75 H. pylori‐infected mucosa biopsies classified into grades I～III gastritis as per our previous study. The number of γδ‐ and 45 RO‐positive T cells were determined by immunostaining. Gastric mucosal anti‐H. pylori urease specific antibodies and interleukin (IL)‐1β, IL‐2, 4, 7, 10 and IL‐12 levels were assayed by enzyme‐linked immunosorbent assay (ELISA). CC chemokine receptor 2 (CCR2) expression levels, migration, and cytokine production in γδ T cells stimulated by H. pylori urease were also evaluated. Results: The γδ T cell count was significantly higher in grade III gastritis which exhibits strong immunoglobulin (Ig)A and IgG responses to H. pylori urease with lymphoid follicles than in other groups. γδ T cell count was significantly correlated with IL‐1β and interleukin‐7 (IL‐7) levels in the gastric mucosa. H. pylori urease immunoreactivity was detected in lamina propria of grade III gastritis, along with many γδ T cells. After H. pylori eradication therapy, the γδ T cell count in grade III gastritis significantly decreased. H. pylori urease stimulated significant increases in CCR2 expression levels, although to a lesser degree than those induced by IL‐7 stimulation in both peripheral and mucosal γδ T cells. Interferon (IFN)‐γ and IL‐10 production was also stimulated by H. pylori urease in peripheral γδ T cells. Conclusions: Gastric mucosal increases in IL‐7 and IL‐1β closely corresponded to the accumulation of γδ T cells in gastric mucosa. An association was also seen between γδ T cell accumulation and H. pylori urease‐specific Ig levels.     

Chronic Gastritis and Bone Mineral Density in Women

We conducted a cross-sectional study of bone mineral density in women with Helicobacter pylori gastritis or autoimmune gastritis. Eighty-five patients were enrolled: 24 patients (mean age 55.2 ± 13.5 years) with autoimmune gastritis, 34 patients (mean age 63.7 ± 7.3 years) with H. pylori gastritis, and 27 H. pylori-negative patients with normal gastric mucosa (mean age 62.5 ± 7.0 years). Gastric mucosa was evaluated by histology and immunohistochemistry. Bone mineral density was measured by dual-energy X-ray absorptiometry. Autoimmune gastritis patients presented severe gastric body mucosa atrophy, based on the absence of parietal cells in 15 (62.5%) patients and the presence of only scattered parietal cells in the remaining nine (37.5%) patients. Among the H. pylori gastritis patients, 21 (62%) presented with different degrees of gastric mucosa atrophy. Bone mineral densities (mean ± SD, g/mm²) were not different among patients with autoimmune gastritis and H. pylori gastritis and the controls. Our results suggest that H. pylori-associated gastritis and autoimmune gastritis would not to be risk factors for decreased bone mineral density in women.     

Expression of COX‐1, COX‐2 and inducible nitric oxide synthase in superficial gastritis,mucosal dysplasia and gastric carcinoma

OBJECTIVE : To investigate the significance of the expression of cyclooxygenase‐1 (COX‐1), cyclooxygenase‐2 (COX‐2) and inducible nitric oxide synthase (iNOS) in superficial gastritis, gastric mucosal dysplasia and gastric carcinoma, and to study the relationship between COX‐2, iNOS, gastric carcinoma and Helicobacter pylori infection. METHODS : Polyclonal antibodies to COX‐1, COX‐2 and iNOS were used detect their expression and the status of H. pylori infection in 92 specimens of paraffin‐embedded gastric tissue. Of the 92 patients, 33 had superficial gastritis, 30 had gastric mucosal dysplasia and 29 had gastric cancer. Helicobacter pylori was detected by toluidine blue staining. RESULTS : Expression of COX‐2 and iNOS in gastric cancer (65.5%, 62.1%) was significantly higher than that in gastritis (18.2%, 18.2%; P < 0.01). Expression of COX‐2 and iNOS in gastritis with H. pylori infection was higher than that in gastric mucosal dysplasia with H. pylori infection. The expression of COX‐2 and iNOS occurred concomitantly in gastritis, dysplasia and gastric cancer. CONCLUSION : Inflammation and H. pylori infection may be able to stimulate the expression of COX‐2 and iNOS, which might be involved in gastric carcinogenesis.     

Gastric mucosal proliferative and total tyrosine kinases activities increase in Helicobacter pylori-induced chronic gastritis

Background. The intestinal type of gastric cancer is thought to originate from cancer precursor lesions, progressing from H. pylori-induced chronic gastritis, atrophic gastritis, to intestinal metaplasia (IM) and dysplasia. Tyrosine kinases (tyr-k) represent the family of proteins that are widely expressed during cell metabolism and are considered as secondary markers for cellular proliferation and malignant transformation. Aim of Study. The aim of the study was to evaluate the correlation between gastric mucosal histopathologic changes, total tyrosine kinases, and proliferative activities in patients with H. pylori infection. Methods. Biopsy specimens from the gastric mucosa of 94 patients were assessed for H. pylori infection, histopathology (according to the Sydney classification), proliferative activity [Ki-67 immunohistochemistry with labeling index (LI) estimation], and total tyr-k activities (ELISA assay kit). Results. Total tyr-k activities and Ki-67 LI were significantly higher in H. pylori (+) than H. pylori (−) group (728.1±175.3 vs 360.1±44.4 pmol P/mg/min. p<0,01 and 20,0±5.8 vs 10.9±1.3 %, respectively). A significant correlation has been observed between the Ki-67 LI and total tyr-k activities in patients with and without H. pylori infection. In cases of gastritis accompanied with atrophic changes or intestinal metaplasia in H. pylori (+) patients, Ki-67 LI and total tyr-k activities were particularly high compared to chronic gastritis without atrophy or intestinal metaplasia. Conclusion. Those results suggest that tyrosine kinases may play an important role in the development of gastric mucosal hyperproliferation in H. pylori-induced gastritis and possibly in early phase of gastric carcinogenesis.     

Relationship between Helicobacter pylori infection and histologic features of gastritis in biopsy specimens in gastroduodenal diseases, including evaluation of diagnosis by polymerase chain reaction assay

We investigated the relationship between Helicobacter pylori infection and the histologic features of gastritis in gastroduodenal disease, and evaluated the diagnostic usefulness of the polymerase chain reaction (PCR) assay for the detection of H. pylori before and after eradication therapy. Endoscopic biopsy specimens from 81 patients with gastroduodenal disease were examined for the presence of H. pylori by culture and histologic examination. Histologic features of gastritis were classified according to the updated Sydney System, and results of the PCR assay were compared with those of histologic examination, using histologic scores. The density of H. pylori was significantly correlated with polymorphonuclear neutrophil activity and chronic inflammation. These findings suggest that the grades of infiltration of polymorphonuclear neutrophil cells and chronic inflammatory cells correspond to the density of H. pylori infection assessed by the updated Sydney System. Patients with positive results on PCR assay and negative results on histologic examination may have a low density of H. pylori because of severe atrophy in the gastric mucosa. Differences in results for the PCR assay and histologic examination were found in 2 of 12 patients in the detection of H. pylori after eradication therapy. According to the results of the PCR assay and histologic features before and after eradication, the gastric tissue-based PCR assay for H. pylori after eradication may be too sensitive to judge successful eradication of H. pylori. Received: October 6, 1998 / Accepted: January 22, 1999     

Helicobacter pylori Infection and Oncogene Expressions in Gastric Carcinoma and Its Precursor Lesions

Although it is fairly well accepted that Helicobacter pylori infection plays a significant role in causing gastric cancer, the exact mechanisms involved in its pathogenesis are unclear. We have examined the relationship between H. pylori infection and oncogene expression in different stages of disease progression from precursor lesions to gastric carcinoma. We used Diff-Quik stain to diagnose H. pylori infection and immunohistochemical stains against c-erbB-2, p53, ras, c-myc, and bcl-2 to determine expression of oncogenes. H. pylori infection was found in all cases of chronic gastritis, atrophic gastritis, intestinal metaplasia, and early gastric carcinoma, and in 16 of 30 (53%) cases of advanced gastric carcinoma. Overexpression of c-erbB-2 was found in 2 (7%) cases of advanced gastric carcinoma, which were H. pylori negative. Suppressor gene, p53, was overexpressed in 3 (30%) cases of intestinal metaplasia, 2 (33%) cases of early gastric carcinoma, and 18 (60%) cases of advanced gastric carcinoma. Of these 18 p53-positive advanced gastric cancer cases, 11 (61%) were H. pylori positive. Expression of ras p21 was found in 4 (40%) cases of H. pylori-negative normal mucosa, 10 (100%) cases of chronic gastritis, 1 (10%) case of atrophic mucosa, 6 (60%) cases of intestinal metaplasia, 2 (33%) cases of nonneoplastic mucosa adjacent to early gastric carcinoma, and 7 (23%) nonneoplastic mucosa adjacent to advanced gastric carcinoma, all of which showed H. pylori. No evidence of expression of either c-myc or bcl-2 was detected in any of the above-mentioned samples. The data suggest that H. pylori infection may increase expression of ras p21 proteins and induce p53 suppressor gene mutation early in the process of gastric carcinogenesis.     

Stem Cell Factor Expressed in Human Gastric Mucosa in Relation to Mast Cell Increase in Helicobacter pylori-Infected Gastritis

We previously reported mast cell increases in H. pylori gastritis. To determine the mechanism, we investigated the kinetics of mast cells and mast cell growth factor (stem cell factor, SCF) in H. pylori-positive and -negative gastric mucosa. Biopsy specimens from 12 H. pylori-negative and 28 positive subjects were examined. Sections were stained for mast cells, proliferating cell nuclear antigen (PCNA), and SCF. Densities of mast cells, PCNA-positive mast cells, and SCF-positive cells were significantly greater in H. pylori-positive than -negative subjects. SCF was expressed in mast cells and fibroblasts. The density of SCF-positive fibroblasts increased in H. pylori-positive gastritis and decreased after cure of infection. SCF mRNA was detected in H. pylori-positive gastric mucosa. Fibroblasts isolated from the normal gastric mucosa expressed SCF mRNA after incubation with H. pylori water extract. SCF may be one of the factors for mast cell increase. Fibroblasts may participate in mast cell increase and inflammation in H. pylori infection.     

Pathological development of the gastric mucosa in Helicobacter pylori‐related diseases

OBJECTIVE : To study the relationship between Helicobacter pylori eradication and the pathological development of the gastric mucosa in H. pylori‐related diseases. METHODS : One hundred and ninety‐one H. pylori‐infected patients were randomly given anti‐H. pylori or non‐anti‐H. pylori medications. Endoscopic examination was carried out 1 year after treatment. Pathological classifications followed the Sydney System. RESULTS : Of the 191 patients, those with chronic inflammation of the gastric mucosa improved (P < 0.05), as did those with atrophy and intestinal metaplasia (P < 0.05). Helicobacter pylori was eradicated in 107 patients, but not in 84 patients. Compared with those patients in whom H. pylori was not eradicated, those with H. pylori eradicated had ameliorated chronic inflammation of the gastric mucosa (P < 0.05) and active inflammation reduced in some cases (P < 0.05). Notwithstanding a stratification of different gastric diseases and different treatments, patients with H. pylori eradicated showed a more marked improvement in mucosal chronic inflammation than did patients in whom H. pylori was not eradicated (P < 0.05). CONCLUSIONS : These results suggest that H. pylori infection is closely related to active inflammation of the gastric mucosa. Helicobacter pylori eradication is beneficial in improving chronic inflammation of the gastric mucosa.     

Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis

The sequence of events associated with the development of gastric cancer has been described as “the gastric precancerous cascade”. This cascade is a dynamic process that includes lesions, such as atrophic gastritis, intestinal metaplasia and dysplasia. According to this model, Helicobacter pylori (H. pylori) infection targets the normal gastric mucosa causing non-atrophic gastritis, an initiating lesion that can be cured by clearing H. pylori with antibiotics or that may then linger in the case of chronic infection and progress to atrophic gastritis. The presence of virulence factors in the infecting H. pylori drives the carcinogenesis process. Independent epidemiological and animal studies have confirmed the sequential progression of these precancerous lesions. Particularly long-term follow-up studies estimated a risk of 0.1% for atrophic gastritis/intestinal metaplasia and 6% in case of dysplasia for the long-term development of gastric cancer. With this in mind, a better understanding of the genetic and epigenetic changes associated with progression of the cascade is critical in determining the risk of gastric cancer associated with H. pylori infection. In this review, we will summarize some of the most relevant mechanisms and focus predominantly but not exclusively on the discussion of gene promoter methylation and miRNAs in this context.     

Differential roles of interleukin‐1β and interleukin‐8 in neutrophil transendothelial migration in patients with Helicobacter pylori infection

Background: Little information is currently available on the contribution of locally generated inflammatory and chemotactic cytokines to endothelial cell activation and subsequent neutrophil transendothelial migration in patients with Helicobacter pylori (H. pylori)‐associated gastritis. Methods: The contents of interleukin (IL)‐1β and IL‐8 in the organ culture supernatants of antral mucosal tissues were measured with an enzyme‐linked immunosorbent assay. The effects of the endogenous IL‐1β and IL‐8 in mucosal tissues on neutrophil adherence and transendothelial migration were investigated using an experimental model of human umbilical vein endothelial cells (HUVEC). Results: The contents of IL‐1β and IL‐8 in organ cultures of antral mucosal tissues were significantly higher in patients with H. pylori infection than in those without infection. The organ culture supernatants from H. pylori‐positive patients induced the expression of intercellular adhesion molecule‐1 mRNA in HUVEC with increased binding of neutrophils, and these stimulatory effects were inhibited when HUVEC were pretreated with a nuclear factor‐κB inhibitor, MG‐132. Moreover, neutrophil adherence to HUVEC induced by the supernatants decreased after preincubation with neutralizing anti‐IL‐1β antibody. As compared with the supernatants from H. pylori‐negative patients, the samples from H. pylori‐positive patients exhibited a significantly higher chemotactic activity for neutrophils, which was inhibited almost completely by preincubation of the supernatants with anti‐IL‐8 antibody. Conclusions: Locally generated IL‐1β and IL‐8 could coordinate with each other during the process of neutrophil infiltration into the gastric mucosa in patients with H. pylori infection.     

Helicobacter pylori infection accelerates human gastric mucosal cell proliferation

Helicobacter pylori causes chronic atrophic gastritis and intestinal type gastric cancer arises against a background of atrophic gastritis. Increased proliferation of epithelial cells is an important indicator of increased risk for gastric adenocarcinoma. We investigated gastric mucosal cell proliferation inH. pylori-associated gastritis and the effect of eradication therapy on this proliferation in 45 patients endoscopically diagnosed (31 with persistent eradication and 14 in whomH. pylori) recurred.H. pylori status was determined by culture and histology in biopsied specimens from the gastric antrum and corpus. Eradication of the infection was defined as reversal to negative on both tests. In vitro Ki-67 immunostaining of endoscopic biopsy specimens was used to measure mucosal cell proliferation inH. pylori-associated gastritis before and after therapy. The proliferative zone was defined as the distance of Ki-67-positive gastric epithelial cells between the highest and the lowest cells. In patients in whomH. pylori was eradicated, cell proliferation in both the antral and corpus mucosa had decreased 4 weeks after completion of the eradication therapy (P<0.01,P<0.001), and 6 months later, it had markedly decreased (P<0.05,P<0.05) and returned to normal. In patients in whomH. pylori recurred, only antral epithelial cell proliferation was reduced 4 weeks after eradication therapy, but whenH. pylori recurred, determined by culture and histology, cell proliferation level was the same as that before eradication. These results suggest thatH. pylori infection accelerates cell proliferation in gastric mucosa and may play a causal role in the chain of events leading to gastric carcinoma.     

Suppressive effect of rice extract on Helicobacter pylori infection in a Mongolian gerbil model

Background Rice extract has been shown to protect gastric mucosa from stress-induced damage. In this study, the antibiotic effect and the anti-inflammatory effect of orally administered aqueous rice extract on Helicobacter pylori infection and H. pylori-induced gastritis, respectively, in Mongolian gerbils were investigated.Methods Fifty specific-pathogen-free male Mongolian gerbils, seven weeks old, were divided into four groups: uninfected, untreated animals (group A); uninfected, rice extract-treated animals (group B); H. pylori-infected, untreated animals (group C); and H. pylori-infected, rice extract-treated animals (group D). Group C and D animals were killed 12 weeks after H. pylori infection (i.e., at 19 weeks of age) and group A and B animals were also killed at age 19 weeks. The stomachs were removed for histopathological examination with hematoxylin-and-eosin staining and anti-5-bromo-2-deoxyuridine (BrdU) immunostaining, and to determine the bacterial burden. Serum anti-H. pylori antibody titers were also tested.Results In groups A and B, the gastric mucosa showed no inflammatory cell infiltration and a few BrdU-reactive cells. Group C animals developed marked chronic active gastritis in the gastric mucosa, and BrdU-labeled cells in the gastric mucosa markedly increased in number. In group D animals, a significant reduction occurred in the degree of neutrophilic polymorphonuclear cell infiltration into the gastric mucosa, in the BrdU-labeling indices of gastric epithelial cells, and in anti-H. pylori antibody titers in the serum (P < 0.01), compared with although H. pylori was not completely eradicated.Conclusions The rice extract was effective in suppressing inflammation and epithelial cell proliferation in the gastric mucosa in H. pylori-infected Mongolian gerbils. The rice extract has potential to exhibit a protective effect on H. pylori-related gastric mucosal diseases.     

Evaluation of endoscopic and histological findings in Helicobacter pylori-positive Japanese young adults

Background and Aim: Many studies have shown that Helicobacter pylori infection is associated with chronic gastritis, peptic ulcers and gastric carcinoma in adults. However, little is known about these associations in the younger population. The aim of this study was to clarify endoscopic and histological findings in H. pylori‐positive young adults. Methods: Two hundred consecutive outpatients younger than 29 years old undergoing esophago‐gastroduodenal endoscopy at four hospitals between 2001 and 2002 were eligible for this study. At endoscopy, three biopsy specimens were obtained from the mid‐antrum, the angulus and the mid‐corpus. Endoscopic and histological interpretations were based on the updated Sydney System. H. pylori infection was determined by histology and serology. Results: The rates of H. pylori infection were 1.2% (1/86) in normal, 95.8% (46/48) in gastritis, 97.8% (45/46) in duodenal ulcers, 100% (17/17) in gastric ulcers, and 100% (3/3) in gastric carcinomas. Endoscopic findings in 112 H. pylori‐positive patients were 25 normal (22.3%), 38 atrophy (33.9%), 18 erosion (16.1%), and 31 nodularity (27.7%). Histological findings of H. pylori‐positive patients in the anturm revealed mononuclear cell and neutrophil infiltration in 100%, and atrophy in 27.7%. Histological findings of H. pylori‐positive patients in the corpus revealed mononuclear cell infiltration in 75%, neutrophil infiltration in 60.7%, and atrophy in 28.6%. Conclusions: The study shows that H. pylori infection is strongly associated with chronic gastritis and peptic ulcers, and that histological corpus gastritis was found with high frequency in Japanese young adults.