Gastric epithelial cell turnover and mucosal protection in Japanese children with Helicobacter pylori infection

Background In adults, epithelial cell proliferation and apoptosis of the gastric mucosa are induced by Helicobacter pylori infection and are associated with gastric atrophy or gastric carcinoma. In children, there are few studies about such epithelial changes. To elucidate the role of H. pylori infection in gastric mucosal inflammation, we immunohistochemically examined gastric mucosa of Japanese children.Methods Biopsy specimens obtained from the gastric antrum and corpus of H. pylori-infected (n = 13) and noninfected children (n = 15) were studied for immunolocalization of Ki-67, single-strand DNA, manganese superoxide dismutase (Mn-SOD), and CD68, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling. In 10 patients with successful eradication, pre- and posttreatment results were compared.Results In both gastric antrum and corpus, neutrophil and mononuclear cell infiltration, epithelial cell proliferation, and apoptosis significantly increased in H. pylori-infected patients, predominantly in the antrum. In the antrum of H. pylori-infected patients, there was positive correlation between the degrees of neutrophil infiltration and cell proliferation (P < 0.05) or apoptosis (P < 0.05). H. pylori eradication improved mucosal inflammation, cell proliferation (P < 0.001), and apoptosis (P < 0.01) in the antrum. Mn-SOD immunoreactivity and CD68-positive macrophages in the antrum, which significantly increased in H. pylori-infected patients, decreased after the eradication.Conclusions H. pylori infection induced gastric mucosal inflammation and epithelial cell turnover in children. Moreover, gastric mucosal defense mechanism against H. pylori infection was activated. H. pylori eradication in childhood might prevent the accumulation of gastric epithelial cell damage.     

Expression of NF-κB in Helicobacter pylori Infection

Helicobacter pylori colonizes the gastric mucosa in humans and causes chronic gastritis. NF-κB has a key role as a mediator in mucosal inflammation. In this study, we examined the expression of NF-κB in the antral epithelial cells of H. pylori-infected and H. pylori-uninfected biopsies and examined these processes in relationship with grade and activity of gastritis, density of H. pylori, presence of the intestinal metaplasia, and atrophy. Fifty biopsies (35 H. pylori-positive patients and 15 H. pylori-negative controls) were studied. NF-κB immunohistochemical stain was performed. NF-κB activity in H. pylori-infected biopsies were markedly enhanced compared with uninflamed biopsies (P = 0.001). We also found positive correlation NF-κB expression with severity of gastritis (according to Sydney score) (P = 0.001), activity of gastritis (P = 0.046) and H. pylori load (P < 0.001), and atrophy (P = 0.004). We did not find a significant relationship between NF-κB and the presence of intestinal metaplasia (P = 0.355). These findings suggested that expression of NF-κB has an important role in H. pylori gastritis.     

Association Between Gastric Atrophy and Helicobacter pylori Infection in Japanese Children: A Retrospective Multicenter Study

The purpose of this study was to determine whether Helicobacter pylori infection and mucosal inflammation result in gastric atrophy in Japanese children. A total of 196 patients ages 1–16 years were retrospectively studied: 131 patients were infected with H. pylori and 65 patients were uninfected. Antral (n = 196) and corpus biopsy specimens (n = 70) were investigated based on the Updated Sydney system. In both the antrum and corpus, H. pylori-infected patients showed significantly higher degrees of inflammation and activity of gastritis, compared with noninfected patients. The prevalence of grade 2 or 3 atrophy in the antrum was 10.7% in H. pylori-infected patients and 0% in the noninfected patients (P < .01) and in corpus 4.3% and 0%, respectively (P = .20). The frequency of intestinal metaplasia in the 2 study groups was 4.6% and 4.6% in the antrum and 0% and 4.2% in the corpus, respectively. Among H. pylori-infected patients, the antrum showed significantly higher degrees of H. pylori density, inflammation and activity of gastritis, and atrophy than the corpus. In the antrum, atrophy was significantly correlated with activity, whereas in the corpus, atrophy correlated with H. pylori density, inflammation, and activity. H. pylori-induced gastric inflammation can cause atrophy in Japanese children, predominantly in the antrum. It remains to be determined whether H. pylori-infected children with gastric atrophy are at increased risk for gastric cancer.     

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.     

Diagnosis of Helicobacter pylori Infection from Antral Biopsies in Pediatric Patients: Is Urease Test that Reliable?

Our objectives were to determine if the urease (CLO) test alone is a reliable diagnostic test for H. pylori gastritis in children and if the density of H. pylori influences the CLO test result. We performed a combined retrospective and prospective study reviewing the results of CLO-test and histology of gastric mucosal biopsy from 67 patients (35 females) with H. pylori gastritis. Two antral biopsies were inoculated on the CLO-test and two processed for histology to grade the severity of gastritis and H. pylori density. The mean age of patients was 11 years (sd ± 4.53). Only 50 patients tested positive for H. pylori on CLO-test, whereas all patients were positive on histology. %The sensitivity of the CLO-test was 75%. There was a significant association between CLO-test positivity and the density of H. pylori organisms on histology (P < 0.01), and with the severity of gastritis (P < 0.001) by the Pearson chi-square test. However, there was no association between the density of H. pylori and severity of gastritis. In conclusion, the CLO-test is not reliable as a sole diagnostic test for H. pylori gastritis in children because of a significant number of false negatives. Histologic examination of gastric mucosal biopsy is superior to the CLO-test in diagnosing H. pylori infection.     

Histopathology and expression of Ki-67 and cyclooxygenase-2 in childhood Helicobacter pylori gastritis

Background Helicobacter pylori infection has been implicated in many pathobiologic changes that are linked with the pathogenesis of gastric cancer. The majority of studies have been performed in adults; however, H. pylori infection in children may be of greater significance because, in general, it reflects the early phase of infection. We therefore investigated several pathobiologic changes in the gastric mucosa of H. pylori-infected children, including histopathologic features, cell proliferation-associated Ki-67 antigen expression, and cyclooxygenase (COX)-2 expression.Methods Sixty-five children with nonulcer dyspepsia were included; 52 were infected with H. pylori, while the other 13 were free of H. pylori infection. A histopathologic review of biopsy specimens obtained from the gastric antrum was performed according to the updated Sydney system. Immunohistochemical expressions of Ki-67 and COX-2 were scored quantitatively or semiquantitatively.Results The H. pylori-infected group was significantly associated with a higher grade of chronic inflammation, acute inflammation, and glandular atrophy. Ki-67 and COX-2 expressions were found to be significantly higher in the H. pylori-infected group. COX-2 expression was correlated with acute and chronic inflammation and Ki-67 expression. COX-2 expression was observed mainly in the monocytic cells and myofibroblasts in the lamina propria.Conclusions H. pylori-infected children, suggestive of the early phase of infection, exhibit increased gastric epithelial cell proliferation, increased COX-2 expression, and other pathobiologic features that may contribute to gastric carcinogenesis. These results have clinical significance for the early introduction of eradication of H. pylori infection in childhood.     

Apoptotic Depletion of Infiltrating Mucosal Lymphocytes Associated with Fas Ligand Expression by Helicobactor pylori-Infected Gastric Mucosal Epithelium: Human Glandular Stomach as a Site of Immune Privilege

H. pylori infection almost invariably results in chronic gastritis, but only a proportion of patients develops severe destruction of epithelial glandular structure or peptic ulcer. To confirm the recent data obtained in testis and eye, showing that Fas ligand is involved in the phenomenon of immune privilege, expression of Fas receptor and its ligand of the stomach was investigated in a panel of gastric biopsies obtained from patients H. pylori-positive (N = 42) and with H. pylori-negative (N = 18) by two-color flow cytometry. The results show that membrane-bound Fas ligand protein is constitutively expressed on freshly isolated human gastric mucosal epithelium coupled with infiltrating lymphocytes. There was significant overexpression of Fas receptor and its ligand, and a higher frequency of apoptotic cell death detected by TUNEL in epithelium and infiltrating lymphocytes in H. pylori-infected patients. These findings suggest that involvement of Fas receptor and its ligand system contributes to some extent to mucosal damage in H. pylori-associated gastritis. However, the more specific findings are apoptotic depletion of invading mucosal lymphocytes associated with Fas ligand expression by gastric epithelium. These provide the first direct quantitative evidence to support Fas receptor counterattack and/or paracrine fratricide as a mechanism of immune privilege in vivo in the H. pylori-infected glandular stomach.     

The vast majority of gastric T cells are polarized to produce T helper 1 type cytokines upon antigenic stimulation despite the absence of Helicobacter pylori infection

Helicobacter pylori infection is associated with chronic infiltration by various cell types, including T cells, whose cytokine production may regulate the inflammatory reaction as well as local immune response to the bacterium. We prospectively analyzed the constituents of the cellular infiltrates and the cytokines produced by T cells in antral biopsies obtained from 73 subjects with and without H. pylori infection, before and after eradication therapy, and compared them with a histological grade of gastritis. We found that T cells predominated in cell number, followed by granulocytes/monocytes and plasma cells in both H. pylori-infected and H. pylori-uninfected subjects. Despite the absence of H. pylori infection, more than 70% of gastric CD4-positive T cells obtained from uninfected tissue produced interferon-γ (IFN-γ) in the cytosol. Upon receptor cross-linking of a CD3 and a CD28 molecule, T cells in both infected and uninfected tissue continuously secreted a far greater amount of IFN-γ than those in peripheral blood mononuclear cell controls for a period of cell culture, whereas the increase in interleukin-4 (IL-4) was very small, and no increase in IL-2 secretion was seen. In H. pylori-infected patients, IFN-γ secretion was correlated with the grade of mononuclear cell infiltration and decreased to an uninfected control level after eradication therapy. We did not see the effect of eradication on IL-4 secretion. Anti-H. pylori antibody of the IgG2 subclass was remarkably increased in H. pylori-infected subjects. These results together suggest that gastric T cells are already differentiated to produce a large amount of IFN-γ by a mechanism unrelated to H. pylori infection. H. pylori infection appeared to activate T cells to secrete even more IFN-γ, which may contribute to maintaining a perpetual inflammation in H. pylori-infected stomach. Received: January 15, 1999 / Accepted: May 28, 1999     

Induction of Chemokine and Cytokine Responses by Helicobacter pylori in Human Stomach Explants

Background: The cytokine response during the acute phase of Helicobacter pylori infection in humans has not been studied. The aim of this study was therefore to investigate the early cytokine responses against H. pylori using cultured human stomach explants as a model of acute infection. Methods: Gastric corpus tissue obtained from 13 adult uninfected and 3 H. pylori-infected patients undergoing gastric surgery due to obesity was used for preparation of mucosal explants. The cultured explants were exposed to different H. pylori     

Characterization of virulence factors of mouse-adapted Helicobacter pylori strain SS1 and effects on gastric hydrophobicity

Gastric infection with Helicobacter pylori results in chronic active gastritis and in some individuals is associated with complications such as peptic ulceration and gastric cancers. A balance between bacterial factors and host responses may determine disease outcome. The mouse-adapted H. pylori strain SS1 has been utilized as a model to study disease pathogenesis. Although chronic gastritis is observed in this murine model of H. pylori infection, other complications of disease seen in the human host (such as peptic ulceration) are not identified. The objectives of this study were to characterize virulence factors of the mouse-adapted H. pylori strain SS1 and determine host responses to infection. Vacuolating cytotoxin activity of H. pylori strain SS1 was determined after incubation of HEp-2 cells with culture supernatant for 24 hr. Polymerase chain reaction was performed to detect the presence of the cagA and cagE genes. Chemokine responses from human gastric epithelial cells infected with H. pylori SS1 were assessed by measurement of the concentration of interleukin-8 in cell-free supernatants. C57BL/6 and gld mice were infected with strain SS1 or sham-infected. Eight weeks following infection, gastric tissues were obtained for histological analysis and surface hydrophobicity was measured by axisymmetric drop-shape analysis. H. pylori strain SS1 was cytotoxin negative, cagA positive, and cagE positive, but induced only a modest interleukin-8 response (684 ± 140 pg/ml) from AGS gastric epithelial cells in comparison to a clinical isolate (4170 ± 410 pg/ml, P < 0.0005). Increased inflammation was observed in the stomachs of H. pylori strain SS1-infected animals compared to uninfected controls. Gastritis was not associated with any disease complications. Despite mucosal inflammation, infected mice did not demonstrate alterations in gastric surface hydrophobicity (42.2° ± 2.2° and 41.4° ± 3.2° for C57BL/6 and gld, respectively) compared to uninfected mice (43.2° ± 2.3° and 39.5° ± 1.6°, respectively). In conclusion, murine infection with H. pylori SS1, which contains putative bacterial virulence factors, results in gastric inflammation. However, the mucosal changes are not associated with alterations in surface hydrophobicity. Therefore, the mouse model of infection with H. pylori, strain SS1 may not serve as an entirely appropriate model to study host factors associated with disease complications.     

Blood leukocyte differential inHelicobacter pylori infection

Helicobacter pylori causes a chronic infection in gastric mucosa, but its systemic effects are largely unknown. Our aim was to characterize the effect ofH. pylori infection and gastric mucosal inflammation on the peripheral blood leukocyte count. An endoscopic series of 96 patients (40 men and 56 women), with a mean age of 62 years (range 49–80) was studied. Endoscopy with eight stepwise biopsies was performed and the occurrence ofH. pylori was studied from sections stained with Warthin-Starry. The severity of inflammation in antral and body mucosa was estimated. The peripheral blood leukocyte count and differential count were determined by the automatic flow cytometric method. The total number of blood leukocytes and the numbers of lymphocytes and basophils were significantly increased inH. pylori-positive patients (N=58), as compared withH. pylori-negative ones (N=38). The total number of blood leukocytes correlated with the numbers of neutrophils, eosinophils, and mononuclear cells in the gastric mucosa. The number of basophils correlated with the number of mucosal neutrophils and mononuclear inflammatory cells. The results show that mucosal inflammation due toH. pylori infection is reflected in the amount of peripheral blood leukocytes. Basophilia suggests involvement of allergic mechanisms inH. pylori gastritis.     

Expression of Progastrin-Derived Peptides and Somatostatin in Fundus and Antrum of Nonulcer Dyspepsia Subjects With and Without Helicobacter pylori Infection

The hypergastrinemia and hyperacidity associated with Helicobacter pylori infection has been explained by either a primary excess of gastrin or a lack of inhibitory influence by somatostatin (SOM). The objective of the present study was to compare the concentrations of fundic and antral SOM- and antral progastrin-derived peptides in nonulcer dyspepsia (NUD) subjects with and without H. pylori infection. Antral and fundic mucosal biopsies were extracted and assayed for SOM and gastrin amide, glycine–extended gastrin (gastrin gly), progastrin, and total gastrin. There was a significant sixfold reduction in antral SOM but no change in fundic SOM content in H. pylori-infected subjects compared to uninfected subjects. Antral gastrin amide concentrations were significantly higher in infected subjects. However, the concentrations of the nonamidated gastrin forms (progastrin and glycine-extended gastrin) were significantly lower in the infected subjects, indicating an increased conversion of the precursor forms of gastrin to amidated gastrin, the type known to stimulate gastric acidity. The present study demonstrates that the elevated gastrin concentrations associated with H. pylori infection may be due to a reduction in the paracrine inhibitory effect of SOM on antral gastrin release. In addition, the posttranslational processing of gastrin to the amidated forms is increased in infected subjects, explaining why the elevation in antral gastrin is confined to the amidated form.     

Significance of cell-surface expression of matrix metalloproteinases and their inhibitors on gastric epithelium and infiltrating mucosal lymphocytes in progression of helicobacter pylori-associated gastritis

Background: Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) have recently been shown to be important in tissue breakdown and remodeling in gut with inflammatory bowel disease. The role of MMPs and TIMPs remains largely unexplored in Helicobacter pylori-associated gastritis (HAG). The aim of this study was to investigate the expression of these proteolytic enzymes in HAG. Methods: Cell-surface or/and intracellular expression of MMP-2, 7, 9 and MT1-MMP and TIMPs (TIMP-2 and -4) was determined in gastric epithelium and infiltrative mucosal lymphocytes (IML) in single endoscopic biopsies from H. pylori-infected (n?=?25) and uninfected (n?=?15) patients. The quantitative analysis was based on the percentage of positive cells detected by flow cytometry. Results: Secreted MMPs and TIMPs as well as membrane type 1-MMP were shown to be localized mainly on the cell surface of both epithelial cells and IML in HAG. H. pylori significantly up-regulated the cell-surface expression not only of MMPs, but also of TIMPs on IML within tissues. The expression of these molecules on IML was correlated with the grade of gastritis. Conclusions: MMPs and TIMPs expressed on gastric epithelium and H. pylori-antigen(s)-stimulated IML may be implicated in mucosal degradation and remodeling of the stomach. These might contribute to the pathogenesis and progression of atrophy and intestinal metaplasia of gastric mucosa.     

Infection with Helicobacter pylori Affects All Major Secretory Cell Populations in the Human Antrum

We have investigated how gastric H. pylori infection affects antrum secretory cell types by studying the expression of secretory proteins in antrum epithelium. Antrum biopsy specimens were prospectively collected from 102 individuals (49 H. pylori-infected). Immunohistochemistry was performed for secretory mucins (MUC5AC, MUC5B, MUC6), Trefoil factor family (TFF)-peptides (TFF1, TFF2), endocrine peptides (gastrin, chromogranin A), and proliferating cells (Ki-67). Protein expression was quantified morphometrically. H. pylori infection was significantly correlated to mucosal inflammation and to epithelial atrophy and proliferation. In H. pylori-infected patients the number of proliferating cells increased significantly, and the zone of proliferating cells shifted toward the surface epithelium of the antral glands. Infection was correlated with decreased MUC5AC, TFF1, and TFF2 expression and increased MUC6 and MUC5B expression. Endocrine cells expressing chromagranin A and gastrin shifted toward the surface epithelium of the antral glands in H. pylori-infected patients. H. pylori infection and concomitant inflammation induced increased epithelial proliferation and triggered coordinate deregulation of secretory cell populations in the antrum. In particular, infection led to a coordinated increase in cells expressing MUC6 and MUC5B at the expense of MUC5AC-producing cells.     

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.     

Correlation between expression of MMP-9 and MMP-3 in Helicobacter pylori infected patients with different gastroduodenal diseases

Background and study aims

Helicobacter pylori (H. pylori) has been implicated in the pathogenesis of most important gastro-duodenal diseases, such as gastritis, peptic ulcer disease (PUD) and gastric cancer. H. pylori upregulates the expression and activity of several matrix metalloproteinases (MMPs) in the gastric mucosa, but the role of MMP-3 and MMP-9 in infected patients with H. pylori have not been clearly defined yet. We examined mucosal MMP-3 and MMP-9 mRNA levels in gastric mucosa of H. pylori infected patients and evaluated the effects of virulence factors cagA and vacA allelic variants on these levels. We also determined correlation between mucosal MMP-3 and MMP-9 mRNA levels and types of disease.

Helicobacter pylori-induced oxidative stress and DNA damage in a primary culture of human gastric mucosal cells

Helicobacter pylori has been identified in the pathogenesis of chronic active gastritis and peptic ulcer disease and is epidemiologically linked to gastric cancer and lymphoma. Our previous studies have demonstrated enhanced production of reactive oxygen species (ROS) in cultured gastric adenocarcinoma cells (ATCC CRL/1739) in association with H. pylori. Recently, we have isolated and cultured normal human gastric mucosal cells (GMC) from H. pylori-negative endoscopic biopsies. The integrity of these mucosal cells was determined by periodic acid–Schiff staining. We assessed the effects of various H. pylori strains including 60190 (a 87-kDa cytotoxin producing strain), ATCC 43504, and 60190-v1 (in which the cytotoxin gene has been disrupted) on the primary culture of human gastric mucosal cells. The induction of ROS and DNA fragmentation in the mucosal cells in association with these H. pylori strains were assessed by cytochrome c reduction (an index of superoxide anion production), hydroxyl radical production, and DNA fragmentation. Following incubation of the mucosal cells with 1:0.5 and 1:1 ratios of H. pylori strain 60190, approximately 6.2- and 9.9-fold increases were observed in cytochrome c reduction, respectively, as compared to mucosal cells in the absence of H. pylori, demonstrating the production of superoxide anion. The detection of hydroxyl radicals based on the formation of 2,3-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid was determined by using a high-performance liquid chromatograph equipped with an electrochemical detector. Approximately 3.5- and 7.7-fold increases in hydroxyl radical production were observed following incubation of the mucosal cells with 1:0.5 and 1:1 ratios of H. pylori, respectively. Approximately 3.6- and 4.5-fold increases in DNA fragmentation were observed in gastric mucosal cells following incubation with 1:0.5 and 1:1 ratios of H. pylori, respectively. The effects of culture supernatant preparations from H. pylori strains 60190 and 60190-v1 on the enhanced production of ROS and increased DNA fragmentation in mucosal cells were also investigated. Culture supernatant preparations, the prime source of the 87-kDa cytotoxin, from both H. pylori strains 60190 and 60190-v1 were extracted under identical conditions to determine the role of 87-kDa cytotoxin on the enhanced production of ROS and DNA fragmentation. The cytotoxin rich-H. pylori strain 60190 induced greater production of ROS and DNA fragmentation in mucosal cells as compared to the supernatant preparation from H. pylori strain 60190-v1, in which the cytotoxin gene has been disrupted. This study demonstrates that H. pylori induces enhanced production of ROS and DNA damage in association with human gastric mucosal cells andthat the 87-kDa cytotoxin protein plays a prime role in the induction of oxidative stress and DNA damage.     

Enhanced levels of C-X-C chemokine,human GROα, in Helicobacter pylori-associated gastric disease*

C-X-C Chemokines play an important role for neutrophil extravasation through microvessels. Although the level of interleukin (IL)-8 is known to increase in the Helicobacter pylori-infected gastric mucosa, another C-X-C chemokine, GROα, has not been evaluated in the H. pylori-associated gastric mucosal injury. The present study was designed to investigate gastric contents of GROα in relation to those of IL-8 in the gastric mucosa of H. pylori-infected peptic ulcer patients. Thirty-eight patients with gastric ulcer and 41 with gastritis underwent endoscopy with informed consent and 49 were found to be H. pylori positive and 30 H. pylori negative. Biopsies from the gastric corpus were performed in each patient to examine the H. pylori colonization by bacterial culture, the rapid urease test and histological specimens as well as measurement of the contents of human GROα and IL-8. Helicobacter pylori infection was eradicated in 21 patients by triple therapy (lansoprazole 30mg, amoxycillin 2.0g, clarithromycin 600 mg; 2 weeks). The samples for GROα and IL-8 assay were homogenized in 0.02% aprotinin containing phosphate-buffered solution and the mucosal contents of GROα and IL-8 in the supernatants were quantified by sandwich enzyme immunoassay methods. The levels of GROα and IL-8 in H. pylori-positive gastric mucosa were significantly higher than those in the H. pylori-negative mucosa. There was a significant linear correlation between the levels of GROα and IL-8 (r= 0.798, P < 0.01). After the eradication of H. pylori by the triple therapy, the levels of GROα and IL-8 were significantly decreased. The GROα showed an increase in the H. pylori-positive gastric mucosa in a similar fashion as IL-8 contents, suggesting a pathogenetic role for GROα in H. pylori-associated gastric mucosal injury.     

Helicobacter pylori CagA-positive Strains Affect Oxygen Free Radicals Generation by Gastric Mucosa

Background: Helicobacter pylori plays a key role in production of reactive oxygen metabolites (ROMs). However, the importance of virulent CagA-positive H. pylori strains remains to be determined. The aim of this study was to assess ROMs production in gastric biopsies of patients infected by H. pylori. Results were correlated to CagA status and acute inflammatory infiltration. Methods: Patients undergoing gastroscopy were enrolled. H. pylori infection was assessed by histology and ¹³C urea breath test. CagA status was assessed through serology. ROMs were assayed in gastric biopsies by luminol-enhanced chemiluminescence (CLS). Gastric mucosal inflammation was histologically graded and neutrophils were individually counted. Macroscopical damage was scored according to a modified Lanza score. Results: 40 out of 60 patients evaluated were H. pylori (HP) positive. Of the 40 infected patients, 24 were CagA-positive. CLS emission was significantly higher in HP-CagA-positive patients than in HP-CagA-negatives and uninfected. ROMs production showed a significant correlation to neutrophil infiltrate in all groups. Conclusions: Gastric mucosa of patients infected by HP-CagA-positive strains is characterized by a higher generation of ROMs and by greater neutrophil counts than that observed in HP-CagA-negative subjects. Since ROMs production is associated with DNA oxidative damage, a long-term stimulation by these strains might be relevant in the pathogenesis of gastric malignancies. Assessment of CagA status might be useful to discriminate patients in which H. pylori eradication is advisable.     

Inflammation of the gastric remnant after gastrectomy: mucosal erythema is associated with bile reflux and inflammatory cellular infiltration is associated with Helicobacter pylori infection

Background Controversy exists concerning the role of bile reflux and Helicobacter pylori (H. pylori) infection in the development of inflammation of the gastric remnant after gastrectomy. This study was designed to investigate association of bile reflux and H. pylori infection or both with inflammatory changes in the gastric remnant.Methods A questionnaire on GI symptoms was returned by 200 gastrectomy patients, and 24-h bilirubin monitoring in the gastric remnant was performed on 55 patients with Bilitec 2000. Upper GI endoscopy evaluated reflux gastritis in the gastric remnant, and the presence of H. pylori infection and chronic, active inflammatory cellular infiltration in the biopsy specimens were examined microscopically with the updated Sydney system.Results No difference in the incidence of GI symptoms was observed among individual gastrectomy patients. Bile reflux was lower in patients who had undergone a gastrectomy with jejunal interposition, a pylorus-preserving gastrectomy, and a gastrectomy with Roux–Y anastomosis than those who had undergone a Billroth-II (B-II) anastomosis (P < 0.05). Endoscopy showed positive correlation between mucosal erythema and bile reflux (P < 0.001). No correlation was observed between the mucosal erythema and chronic and active inflammatory cellular infiltration. Infection of H. pylori correlated with chronic and active inflammatory cellular infiltration (P < 0.001). Bile reflux did not correlate with the severity of chronic and active inflammatory cellular infiltration or H. pylori infection.Conclusions Bile reflux into the gastric remnant was observed by Bilitec 2000. Mucosal erythema and chronic, active inflammatory cell infiltration in the gastric remnant after gastrectomy may be caused by bile reflux or H. pylori infection, respectively.