Showing papers on "Chronic gastritis published in 1997"

Helicobacter pylori cagA + Strains and Dissociation of Gastric Epithelial Cell Proliferation From Apoptosis

Abstract: Background: Infection with Helicobacter pylori induces chronic gastritis in virtually all infected persons, and such gastritis has been associated with an increased risk of developing gastric cancer. This risk is further enhanced with cagA + (positive for cytotoxin-associated gene A) H. pylori strains and may be a consequence of induced gastric cell proliferation and/or alteration in apoptosis (programmed cell death) in the gastric epithelium. Purpose: To determine whether the H. pylori cagA genotype and another virulence-related characteristic, the vacA (vacuolating cytotoxin A) s1a genotype, differentially affect epithelial cell proliferation, apoptosis, and the histologic parameters of inflammation and injury, we quantitated these characteristics in infected and uninfected persons. Methods : Fifty patients underwent upper gastrointestinal endoscopy, and biopsy specimens were taken. Apoptotic cells in the specimens were quantitated after terminal deoxynucleotidyl transferase labeling of DNA fragments with digoxigenin-deoxyuridine triphosphate; epithelial cell proliferation was scored by immunohistochemical analysis of the proliferation-associated antigen Ki-67. Antibodies directed against H. pylori and CagA protein were measured in the serum of patients by means of enzyme-linked immunosorbent assays. Analysis of H. pylori genomic DNA, by use of the polymerase chain reaction, was performed to determine the cagA and vacA genotypes. Acute and chronic inflammation, epithelial cell degeneration, mucin depletion, intestinal metaplasia, glandular atrophy, and vacuolation were each scored in a blinded manner. Reported P values are two-sided. Results: Persons harboring cagA + strains (n = 20) had significantly higher gastric epithelial proliferation scores than persons infected with cagA - strains (n = 9) or uninfected persons (n = 21) (P = .025 and P<.001, respectively), but the difference in cell proliferation between the latter two groups was not statistically significant. The number of apoptotic cells per 100 epithelial cells (apoptotic index) in persons infected with cagA + strains was lower than in persons infected with cagA - strains (P =.05). Apoptotic indices in the cagA + group were similar to those in the uninfected group (P =.2). Epithelial cell proliferation was significantly correlated with acute gastric inflammation, but only in the cagA + group (r =.44; P =.006). The cagA + and vacA s1a genotypes were found to be concordant, confirming the close relationship between these virulence-related genotypes. Conclusions: Gastric mucosal proliferation was significantly correlated with the severity of acute gastritis in persons infected with cagA + vacA s1a strains of H. pylori. This increased proliferation was not accompanied by a parallel increase in apoptosis. Implications: Increased cell proliferation in the absence of a corresponding increase in apoptosis may explain the heightened risk for gastric carcinoma that is associated with infection by cagA + vacA s1a strains of H. pylori.

Different cytokine profile and antigen-specificity repertoire in Helicobacter pylori-specific T cell clones from the antrum of chronic gastritis patients with or without peptic ulcer.

Abstract: Helicobacter pylori (Hp) infection almost invariably results in chronic antral gastritis, but only a proportion of patients develop peptic ulcer. Some Hp strains may be more ulcerogenic than others, but some ulcerogenic mechanisms may also depend on the type of the host immune response. In this study, the antigen specificity and the cytokine profile of 53 Hp-specific CD4+ T cell clones derived from the antral mucosa of five patients with Hp-induced uncomplicated chronic gastritis (CG) were assessed and compared with those of 34 Hp-specific CD4+ T cell clones derived from six Hp-infected patients with chronic gastritis and peptic ulcer (CG-PU). The majority (28/34; 82%) of gastric Hp-specific T cell clones from CG-PU patients expressed the Th1 profile and 17 (all Th1) of the 34 clones were specific for cytotoxin-associated protein (CagA). In contrast, 34 (64%) of the 53 Hp-specific gastric T cell clones derived from CG patients were able to secrete both Th1 and Th2 cytokines (Th0 profile) and only 36% expressed a polarized Th1 profile. The majority (85%) of Hp-specific clones from CG patients recognized Hp antigens other than CagA, since 13/53 (25%) were specific for urease, 6 (11%) for VacA, 6 (11%) for HSP and 20 (38%) for other undefined Hp antigens. Results provide evidence that the type of T helper cell response against Hp may vary according to the antigen involved and suggest that a polarized Th1 response may play a role in the genesis of peptic ulcer, whereas a local Th0 response, including interleukin-4 production, may represent an individual host factor which contributes to lower the degree of gastric inflammation and prevent ulcer complication.

Helicobacter pylori and the risk and management of associated diseases: gastritis, ulcer disease, atrophic gastritis and gastric cancer

Abstract: This review addresses the role of H. pylori and the effect of H. pylori eradication on gastritis, peptic ulcer disease, atrophic gastritis and gastric cancer. Specific emphasis is given to various factors that influence the clinical course of this infection. H. pylori induces chronic gastritis in virtually all infected subjects. This inflammation can lead to peptic ulceration and atrophic gastritis in a considerable number of infected subjects. A minority eventually develops gastric cancer. The risk of such complications depends upon the severity of gastritis, which is determined by various host- and bacteria-related factors. Among bacterial factors, most of the evidence addresses the cagA pathogenicity island, the presence of which has been associated with more severe gastritis, peptic ulceration, atrophic gastritis and gastric cancer. Among host factors, most of the evidence focuses on acid production in response to H. pylori infection. An increase in acid secretion limits H. pylori gastritis to the antrum at the risk of duodenal ulcer disease; a reduction allows more proximal inflammation at the risk of atrophic gastritis, gastric ulcer disease, and gastric cancer. Gastritis and atrophy negatively influence acid secretion. H. pylori eradication is required in peptic ulcer disease and may be advocated in patients on profound acid suppressive therapy; it has been shown to cure gastritis and prevent ulcer recurrence. Further study is required to determine the efficacy of H. pylori eradication in the primary and secondary prevention of atrophic gastritis and gastric cancer.

Equally high prevalences of infection with cagA-positive Helicobacter pylori in Chinese patients with peptic ulcer disease and those with chronic gastritis-associated dyspepsia.

Abstract: Approximately 60% of Helicobacter pylori isolates in the Western world possess the cytotoxin-associated gene A (cagA). cagA-positive H. pylori is found to be associated with peptic ulcer disease (PUD) and gastric adenocarcinoma. To investigate the cagA status of H. pylori isolates from Chinese patients with PUD and chronic gastritis (CG), H. pylori populations from 83 patients, 48 with PUD and 35 with CG, were assessed by two different cagA-specific PCRs, Southern blotting, and colony hybridization. The combined results from PCR, Southern blotting, and colony hybridization indicate a prevalence of cagA-positive H. pylori isolates of 98% (47 of 48) among Chinese PUD patients and 100% (35 of 35) among Chinese CG patients. Amplification with primer sets 1 and 2 yielded 52 and 95% of the 82 cagA-positive Chinese H. pylori, respectively. In contrast, the sensitivity of cagA-specific PCR for cagA-positive H. pylori isolates from Dutch patients with primer set 1 was 92% (112 of 122) and that with primer set 2 was 91% (50 of 55). The prevalence of cagA-positive H. pylori populations in Chinese patients with PUD and CG is almost universally high. Therefore, cagA cannot be used as a marker for the presence of PUD in Chinese patients. Our data further suggest that allelic variation in cagA may exist and that distinct H. pylori genotypes may circulate in China and Western Europe.

Helicobacter pylori independent chronological change in gastric acid secretion in the Japanese

Abstract: Background —Gastric acid secretion in Japanese subjects decreases with aging. One of the possible causative mechanisms of this attenuated acid secretion is speculated to be a Helicobacter pylori induced chronic gastritis. The infection rate of this microorganism has decreased recently in Japan. Aims —To investigate whether gastric acid secretion has altered over the past 20 years, and if so, what the influence of H pylori infection might be in the Japanese population. Subjects and methods —Gastric acid secretion, serum gastrin and pepsinogen I and II concentrations, and H pylori infection were determined in 110 Japanese subjects in both the 1970s and 1990s. Results —Basal acid output as well as maximal acid output have greatly increased over the past 20 years, not only in individuals with H pylori infection but also in those without infection. Furthermore, subjects with H pylori infection tended to show decreased gastric acid secretion in comparison with those without infection, particularly in geriatric subjects. There was a positive correlation between gastric acid secretion and serum pepsinogen I concentrations. Conclusions —In Japan, both basal and stimulated gastric acid secretion have increased over the past 20 years; some unknown factors other than the decrease in H pylori infection may play an important role in this phenomenon.

Helicobacter pylori in gastro-oesophageal reflux disease: causal agent, independent or protective factor?

Abstract: Helicobacter pylori causes chronic gastritis with variable activity and topographic distribution. Patient age at acquisition, expression of gastritis, strain virulence, host factors, and environmental factors determine the outcome of the infection. Well established consequences are peptic ulcer disease (PUD) and gastric neoplasia.1-4 As duodenal ulcer is often associated with gastro-oesophageal reflux disease (GORD),5 and antral gastritis is a frequent finding in patients with reflux disease,6 H pylori infection may be a common cause of both conditions. Our aim was to explore the strength of the postulate that H pylori is a causal factor in GORD by reviewing publications on epidemiological studies, clinical observations or treatment trials, and identifying possible pathogenic mechanisms. Currently, we have no clear data to show that patients with GORD are more frequently infected by H pylori than controls, neither in adults nor in children.7 Indeed, a recent well designed case control study from Japan showed a significantly lower incidence of H pylori infection in patients with reflux oesophagitis than in age and sex matched controls.8 This finding is supported by one of our own studies.9 The prevalence of both H pylori infection and GORD increases with age.10 11 Male sex is a risk factor for GORD,12 but the prevalence of H pylori is equally distributed between men and women.10 12 H pylori is able to colonise Barrett’s epithelium. Many uncontrolled studies showed H pylori prevalence rates similar to those in the background population.7 Also, in a controlled study the prevalence of H pylori infection was similar in patients with Barrett’s oesophagus and controls.13 However, patients with Barrett’s oesophagus and an ulcer within the columnar metaplasia were more frequently infected by H pylori than those without ulcers.14 The prevalence of H pylori infection is decreasing …

Gastric mucosal secretion of interleukin-10: relations to histopathology, Helicobacter pylori status, and tumour necrosis factor-alpha secretion.

Abstract: BACKGROUND: Interleukin-10 (IL-10) is an 18 kDa peptide with a range of anti-inflammatory and immunosuppressive properties. AIM: To determine whether this cytokine is involved in gastric mucosal inflammation in Helicobacter pylori infection. METHODS: The production of IL-10 by antral mucosal biopsy specimens during short term in vitro culture was determined by measuring IL-10 content of supernatants by enzyme linked immunosorbent assay (ELISA). H pylori status was determined by serology and histology, with gastritis scored using the Sydney system. Tumour necrosis factor-alpha (TNF-alpha) content of supernatants was also determined in a subgroup of patients. RESULTS: IL-10 secretion was significantly greater in patients with H pylori associated chronic gastritis than in patients who were H pylori negative with normal mucosa/reactive changes, and those with H pylori negative chronic gastritis (p < 0.01 and < 0.05 respectively). There was a significant correlation overall between IL-10 secretion and chronic inflammation score (r = 0.40). Secretion of TNF-alpha, which was significantly higher in H pylori infected patients than uninfected patients with a normal mucosa (p < 0.04), correlated with scores for chronic inflammation and activity (r = 0.39 and 0.38 respectively), but was only weakly correlated with IL-10 secretion (r = 0.22, NS). CONCLUSIONS: Gastric mucosal production of IL-10 and TNF-alpha are increased in chronic gastritis associated with H pylori infection, and mucosal cytokine secretion varies with important histopathological aspects of gastric inflammation. Whereas the secretion of IL-10 in H pylori infection may be protective, limiting tissue damage caused by inflammation, it may also contribute towards failure of the immune response to eliminate the organism.

Oral Carriage of Helicobacter pylori: A Review

Abstract: Helicobacter pylori is a microaerophilic, motile bacterium, especially adapted to life in the human stomach. The presence of H. pylori in the stomach is strongly associated with chronic gastritis and ulcer disease and is a risk factor for gastric cancers. The microorganism may be transmitted orally and has been detected in dental plaque, saliva, and feces, but the hypothesis that oral microflora may be a permanent reservoir of H. pylori is still controversial. A review of the literature suggests that the recovery of H. pylori in the mouth is probably intermittent, associated with gastroesophageal reflux but not with specific oral disease. Nonetheless, the PCR identification of oral H. pylori may become helpful, particularly in cases of gastritis or ulcer relapse after antimicrobial therapy. Eradication of oral H. pylori by local medication or periodontal procedures would rely on the precise identification of its ecological niche. Within family groups, prophylactic methods should be practiced to avoid oral carriage of H. pylori. The risk of iatrogenic transmission during dental care, however, is already circumscribed by standard professional hygiene procedures.

Histological classification of gastritis and Helicobacter pylori infection: an agreement at last? The International Workshop on the Histopathology of Gastritis.

Abstract: An international workshop has assessed and revised the Sydney System for the reporting of gastritis. Much of the original approach was retained including division into acute, chronic and special forms, and grading of chronic inflammation, polymorph activity, atrophy, intestinal metaplasia and H. pylori density into mild, moderate and marked categories. Visual analog scales have been introduced as a simple guide to grading. The four biopsy sites have been changed to optimize detection of H. pylori, and supplemented by a fifth biopsy from the incisura angularis, the site which is most likely to yield premalignant changes. Chronic gastritis is classified into non-atrophic and atrophic forms with the latter divided into autoimmune (diffuse corpus atrophy) and multifocal. Histological reporting of gastritis should take into account the topographical pattern (antral or corpus predominant), and the final diagnostic term should ideally combine morphology and etiology to maximize the clinical value of gastric biopsy diagnosis.

Helicobacter mustelae-associated Gastric Adenocarcinoma in Ferrets (Mustela putorius furo)

Abstract: Helicobacter pylori in humans is associated with active, chronic gastritis, peptic ulcer disease, and most recently has been linked epidemiologically to gastric adenocarcinoma. A related organism, Helicobacter mustelae, naturally infects ferrets and also causes a persistent gastritis, a precancerous lesion, and focal glandular atrophy of the proximal antrum. In this report, we document the clinical presentation and histopathologic confirmation of H. mustelae-associated gastric adenocarcinoma in two middle-aged male ferrets. The ferret appears to be well suited to study the pathogenesis of naturally occurring Helicobacter sp.-induced gastric adenocarcinoma.

Helicobacter mustelae-associated gastric MALT lymphoma in ferrets

Abstract: Gastric lymphoma resembling gastric mucosa-associated lymphoid tissue (MALT) lymphoma linked with Helicobacter pylori infection in humans was observed in ferrets infected with H mustelae Four ferrets with ante- or postmortem evidence of primary gastric lymphoma were described Lymphoma was diagnosed in the wall of the lesser curvature of the pyloric antrum, corresponding to the predominant focus of H mustelae induced gastritis in ferrets Two ferrets had low-grade small-cell lymphoma and two ferrets had high-grade large-cell lymphoma Gastric lymphomas demonstrated characteristic lymphoepithelial lesions, and the lymphoid cells were IgG+ in all ferrets Lymphoma was confirmed by light chain restriction, which contrasted with the 12:1 kappa lambda ratio observed in H mustelae-associated chronic gastritis H mustelae infection in ferrets has been used as a model for gastritis, ulcerogenesis, and carcinogenesis The ferret may provide an attractive model to study pathogenesis and treatment of gastric MALT lymphoma in humans

Autoantibodies to Gastric Mucosa in Helicobacter pylori Infection

Abstract: Background. Although Helicobacter pylori is recognized as the main cause of chronic gastritis and its associated diseases, very little is known about the pathogenetic mechanisms leading to intestinal metaplasia and atrophic gastritis. Methods. We reviewed the data regarding the possible pathogenetic role played by the anti–H. pylori immune responses in the genesis of atrophic gastritis and intestinal metaplasia. Results. Although only type A (corpus-restricted atrophic gastritis), often associated to pernicious anemia, is considered autoimmune in nature, abundant evidence supports the presence of cellular and humoral autoimmune responses also in patients with H. pylori infection. In a mechanism known as antigenic mimicry, highly conserved immunogenic molecules expressed by infectious pathogens may act as a trigger for the induction of humoral and cellular immune responses that cross-react with host cellular antigens. Numerous studies support the view that H. pylori is very effective in inducing antigenic mimicry, and antibodies against H. pylori have been found to cross-react with both antral mucosal cells (the membrane of the secretory canalicular structures of the parietal cells) and gastrin-producing cells. Such autoantibodies were detected both in human infections and in experimental work in rodents. Conclusions. The detection of antibodies that cross-react with H. pylori and various components of the gastric mucosa provides strong support to the view that immune responses against H. pylori not only participate in the pathogenetic mechanisms leading to atrophy in the progressive atrophic gastritis associated with Helicobacter infection but also in the corpus-restricted autoimmune gastritis.

High seropositivity of anti-CagA antibody in Helicobacter pylori-infected patients irrelevant to peptic ulcers and normal mucosa in Japan.

Abstract: CagA-positive H. pylori is reported to be associated with gastroduodenal disease in Western countries. To evaluate the relationship between CagA and disease, cloning of the entire cagA gene (3771 bp), insertion of a partial fragment (1272 bp) into an expression vector, purification of the recombinant protein, production of an antibody against the recombinant CagA protein through rabbits, and use of the recombinant CagA protein as an antigen, detection of the anti-CagA antibody by western blotting were all performed. Sera of 132 H. pylori-infected patients undergoing endoscopy were studied. Anti-CagA antibodies were detected in 90%, 87%, 90%, 94%, and 93% of patients with gastric ulcer (N = 34), duodenal ulcer (N = 27), chronic gastritis (N = 31), gastric cancer (N = 17), and normal mucosa (N = 15), respectively. High seropositivity of anti-CagA antibody even in individuals with normal mucosa indicated that CagA may not be a unique marker for disease by H. pylori infection in Japan.

Reduced incidence of rectal cancer, compared to gastric and colonic cancer, in a population of 73,076 men and women chronically immunosuppressed.

Abstract: The incidence of gastric, colonic, and rectal cancers was determined in a cohort of 73,076 men and women chronically immunosuppressed after heart or renal transplantation, to test the hypothesis that there would be a reduced incidence of gastric cancer by dampening chronic gastritis secondary to infection caused by Helicobacter pylori. Follow-up was from 1-13 years. No change in the incidence of gastric cancer was found (32 cases observed, 32.86 expected). An increase in colon cancer was found (75 cases observed, 62.27 expected). A significant reduction in the incidence of rectal cancer was found (15 cases observed, 41.5 expected). This led to a chi2 of 16.92 with 1 degree of freedom, significant at the 0.1% level. The effect was greater in men than women and more marked in heart recipients than in those receiving renal transplants. This unexpected finding led to a review of experiments in mice and rats that present evidence for immune promotion of large-bowel cancers induced by carcinogens by gut-associated lymphoid tissue. We conclude that an analysis of immune function in gut-associated lymphoid tissue in the stomach, colon, and rectum in healthy and immunosuppressed patients may lead to a better understanding of immunosurveillance in the colon and immune promotion of rectal cancers.

Analysis of cell damage and proliferation in Helicobacter pylori-infected human gastric mucosa from patients with gastric adenocarcinoma.

Abstract: Helicobacter pylori (HP) infection, a cause of multifocal atrophic gastritis, is considered an important factor related to the evolution of the human gastric mucosa from normal to intestinal-type adenocarcinoma. We examined cell proliferation and both double and single strand DNA damage in situ in 35 patients undergoing gastrectomy for adenocarcinoma with HP-infected gastric mucosa by immunolocalization of Ki-67, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, and in situ nick translation. We also studied the distribution of intraepithelial neutrophils by elastase immunolocalization. HP infection was confirmed in all cases by serum anti-HP antibodies, ureas testing, and histopathological examination. HP-infected gastric mucosa was classified according to the degree of inflammation and intestinal metaplasia. Ki-67, terminal deoxynucleotidyl transferase-mediated labeling, in situ nick translation, and intraepithelial neutrophil indices all increased with the progression of gastritis and were highest in glands with incomplete intestinal metaplasia. All indices were lowest in gastric glands with complete intestinal metaplasia. Significant positive correlations were observed among these markers. Increased proliferative activity in HP-associated chronic gastritis in response to cell damage or injury was clearly demonstrated, suggesting that both HP-associated toxins and intraepithelial neutrophils are important in HP-related gastric epithelial injury. Increased cell turnover associated with incomplete intestinal metaplasia may result in DNA instability and subsequent development of intestinal-type gastric adenocarcinoma in HP-infected mucosa.

Epithelium related deposition of activated complement in Helicobacter pylori associated gastritis.

Abstract: BACKGROUND AND AIMS: It is unknown whether Helicobacter pylori infection activates complement in vivo. Mucosal deposition of various activation products of the complement system may contribute to the pathogenesis of chronic gastritis and was therefore studied by immunohistochemistry. PATIENTS AND METHODS: Ethanol fixed antrum or body gastric tissue sections from 24 patients infected with H pylori (determined by bacterial immunohistochemistry) and 22 uninfected patients were examined by immunofluorescence with monoclonal antibodies to activation neoepitopes in C3b and in the terminal complex (TCC). As a control group, biopsy samples from the gastric stump of 23 Billroth II operated patients were studied. RESULTS: Patchy, bright staining for TCC occurred below the surface epithelium and around the glands in H pylori positive and negative gastritis as well as in stump gastritis but seldom in normal mucosa. Activated C3 was present at the apical face of the surface epithelium, significantly more often in the antrum and body from patients with than without H pylori infection (p = 0.05 and p = 0.03 respectively), and particularly in samples with granulocyte infiltration (p = 0.04). Many bacteria were coated with activated C3 towards the pit openings but seldom within the foveolae. CONCLUSIONS: Local complement activation was shown to take place in simple chronic gastritis, associated as well as unassociated with H pylori infection, and also in stump gastritis. The fact that activated C3 was seldom seen on H pylori within the foveolae, suggested that the bacterium evades complement attack in this location.

Helicobacter pylori gastritis—Epidemiology

Abstract: The acquisition ofHelicobacter pylori is the main cause of chronic gastritis in humans. In Europe, a small proportion (less than 1%) of gastritis cases are caused byH. Heilmannii, and somewhat more (5%) are autoimmune in origin, in which conditionH. pylori may not probably play a role. Recent findings on chronic gastritis andH. pylori acquisition in developed countries can be summarized as: (1)H. pylori gastritis is acquired in childhood and adolescence (age less than 20) in more than 50% of cases; (2) the risk and rate of acquisition is highest in early childhood, after which the rate exponentially declines; (3) new infectious occur in adulthood but are quite rare (annual incidence 0.4%, on average, in Finland); (4)H. pylori gastritis is a birth cohort-related phenomenon; i.e., different cohorts show a rate and prevalence ofH. pylori gastritis that varies between cohorts; (5) the rate and risk ofH. pylori infection is high in cohorts born in the beginning of the century, but is much lower in those born later; (6) this decline is due to a decrease in the rate and risk ofH. pylori acquisition in childhood in particular.H. pylori gastritis—related complications, such as peptic ulcer diseases and gastric cancer, show epidemiological features similar toH. pylori gastritis. Both peptic ulcer and gastric cancer have declined in incidence over time. Gastric cancer is a birth-cohort phenomenon in the same way as isH. pylori gastritis, and the incidence of gastric cancer shows a positive but exponential relationship with the “birth-cohort-specific” prevalence of gastritis in the general population.

Monoclonal antibodies against Helicobacter pylori cross-react with human tissue.

Abstract: Background H pylori is a causative agent of chronic gastritis However, the pathogenic mechanism by which H pylori induces chronic inflammation and epithelial injuries in the gastric and duodenal mucosa is not well known Investigators have recently reported that some monoclonal antibodies against H pylori cross-react with the gastric epithelial cells So, there exists the possibility that the autoimmune mechanism may be involved in the pathogenesis of chronic gastritis caused by H pylori The purpose of his study is to investigate whether the antibodies against H pylori react with human tissues or not, using a large panel of monoclonal antibodies Materials and Methods Two hundred and fourteen monoclonal antibodies against H pylori were produced An immunohistochemical staining of human tissues, including H pylori-infected gastric mucosa, was performed using the antibodies Results Of 214 monoclonal antibodies, 71 antibodies reacted with H pylori in the gastric mucosa Of 71 antibodies, 25 antibodies also reacted with gastric epithelial cells, 11 antibodies reacted with ductal cells of the salivary gland, 11 antibodies reacted with renal tubular cells, and 8 antibodies reacted with duodenal epithelial cells The antibodies which showed cross-reactivity with gastric epithelial cells included those against urease, flagella, lipopolysaccharide, and heat shock protein of H pylori Conclusions It is believed that the autoimmune reaction might be involved in the pathogenesis of chronic gastritis due to H pylori infection, and that the autoimmune reaction induced by H pylori infection might also be involved in the pathogenesis of various diseases in other organs

The immunobiology of Helicobacter pylori gastritis.

Abstract: Helicobacter pylori is the major causative agent of chronic gastritis. It is associated with duodenal and gastric ulcer and with the majority of primary gastric B-cell lymphomas; furthermore, there is a strong epidemiological association with gastric cancer. One intriguing aspect of this infection is the ability of H pylori to persist despite the vast array of host immune responses. This article reviews what is known about the immune responses against H pylori, emphasizing what is generally accepted and applicable while highlighting areas of controversy. The first section delineates the genesis of the inflammatory responses, which initiate with the production of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1, IL-6, and IL-8 and continue with the recruitment of neutrophilic polymorphonuclear cells, lymphocytes, plasma cells, macrophages and eosinophils, and later with the development and recruitment of specifically committed cells (lymphocytes sensitized to H pylori antigens and B cells producing immunoglobulin (Ig)A, IgG, and possibly IgE antibodies against a variety of H pylori surface and flagellar proteins as well as bacterial toxins). The second part of the article focuses on the development of lymphoid follicles in the gastric mucosa, a phenomenon that for the first time links an immune response (the recruitment of mucosa-associated lymphoid tissue [MALT] to the gastric mucosa in response to H pylori infection) with the development of a neoplastic growth (the development of gastric MALT lymphomas). The local and systemic antibody responses are discussed in the light of their potential application in the development of diagnostic tests and vaccines. Particular emphasis is placed on the controversies surrounding the significance of antibodies directed against a 120 to 140 kDa protein apparently associated with more "aggressive" (sometimes also called "ulcerogenic" or "pathogenic") strains of H pylori.

Omeprazole-based Dual and Triple Regimens for Helicobacter pylori Eradication in Children

Abstract: Objective. To evaluate the efficacy and safety of omeprazole-based dual and triple regimens for the treatment of children with Helicobacter pylori infection. Methods. Twenty-two patients (3 with gastric ulcer, 12 with duodenal ulcer, and 7 with nodular gastritis alone) were studied. Twelve ulcer patients also had nodular gastritis. The dual regimen included a 2-week course of omeprazole (0.6 mg/kg twice a day) and amoxicillin (30 mg/kg twice a day) (n = 10), and the triple regimen included the dual regimen plus clarithromycin (15 mg/kg twice a day) (n = 12). In patients with active ulcers, omeprazole once daily was administered for another 4 weeks. Endoscopic biopsies were taken before therapy and 4 weeks after completion of a 2-week course of therapy, and patients were followed for 6 months. The gastritis score (grade 0 to 3) and serum anti-H pylori IgG antibody titers were also determined. Results. The regimens were tolerated by all patients. Eradication rates for the dual and triple regimens were 70% and 92%, respectively. Active ulcers completely healed within 6 weeks. Patients with nodular gastritis alone showed different clinical responses to therapy. Pretreatment histology showed chronic gastritis in all patients. Successful H pylori eradication significantly reduced the mean gastritis score from 2.9 to 1.3, but unsuccessful eradication did not reduce it. The disappearance of antral nodularity often coincided with the success of eradication. Successful eradication significantly decreased pretreatment serum anti-H pyloriIgG antibody titers by 29% at 1 month, by 52% at 3 months, and by 67% at 6 months. Side effects were mild and were reported in 23% of patients. Conclusion. An omeprazole-based regimen is safe and may be a better option for eradication of H pylori in children. Antral nodularity is a macroscopic marker of H pyloriinfection.

Endocrine cell growths in atrophic body gastritis. Critical evaluation of a histological classification

Abstract: The aim of the present study was to evaluate the correspondence of the classification of non-antral endocrine cell growths proposed by Solcia and co-workers with clinical features and non-endocrine mucosal changes. For this purpose, 94 cases of newly diagnosed atrophic body gastritis were investigated using endoscopic biopsies and compared with 18 control subjects. The patients were subdivided into the following four groups according to the most severe pattern of endocrine cell proliferation found in the body mucosa, as shown by chromogranin A immunostaining: group 1, normal pattern (7 cases, 7.5 per cent); group 2, simple hyperplasia (6 cases, 6.5 per cent); group 3, linear hyperplasia (24 cases, 25.8 per cent); group 4; micronodular hyperplasia (56 cases, 60.2 per cent). Adenomatoid hyperplasia was found in only one case, thus precluding further analysis. Patients in groups 1 and 2 had lower acid secretion, higher gastrin level, and higher mean scores in all histopathological variables of chronic gastritis considered by the Sydney system when compared with controls, but did not differ among them in any parameter investigated. When compared with groups 1 and 2, patients of groups 3 and 4 showed higher values of circulating gastrin, higher scores of glandular atrophy, and lower values of acid secretion and of mononuclear and neutrophil inflammatory cell infiltration. Moreover, group 4 patients differed significantly from those of group 3 in their higher gastrin levels and atrophy scores, and lower scores of neutrophil cell infiltration. On the basis of these results, it is proposed that for practical purposes the normal and the simple hyperplasia patterns may be incorporated into a single group. It is concluded that this classification in its simplified form, based on a qualitative histological approach, shows clinical relevance without the need to perform expensive, time-consuming morphometric evaluations.

High prevalence of cytotoxin positive Helicobacter pylori in patients unrelated to the presence of peptic ulcers in Japan

Abstract: Background—It has been reported that infection with vacuolating cytotoxin positive Helicobacter pylori strains is associated with gastroduodenal disease in Western countries. Aims—To evaluate the prevalence of cytotoxin producing strains among patients with H pylori infection in relation to gastrointestinal diseases in Japan. Patients—Ninety seven patients undergoing endoscopy. Methods—A Western blot assay was conducted to detect serum antibodies against the cytotoxin using recombinant cytotoxin (VacA protein) as an antigen. To obtain a purified recombinant cytotoxin, the vacA gene (2233 nucleotides) was cloned into an expression vector to produce the protein (744 amino acids), which was expressed in Escherichia coli. Results—Serum IgG antibodies to the cytotoxin were present in 85%, 95%, 95%, and 100% of infected patients with gastric ulcer (n=26), duodenal ulcer (n=21), chronic gastritis (n=19), and endoscopically normal mucosa (n=14), respectively. Conclusion—The western blot method using recombinant VacA protein is simple and useful for detecting antibody to vacuolating cytotoxin. This method showed antibodies against cytotoxin were highly prevalent, even in subjects with endoscopically normal mucosa in Japan, indicating that the cytotoxin may not be an independent cause of gastrointestinal diseases induced by H pylori infection. Keywords: stomach; Helicobacter pylori; vacA; ulcer; gastritis

Gastric juice levels of lactoferrin and Helicobacter pylori infection

Abstract: Background: Recently, in vitro studies suggested that lactoferrin (Lf) might play an important role in the physiopathology of Helicobacter pylori-associated gastritis. However, whether Lf is present in the gastric juice and its relationship with H. pylori infection have not as yet been reported. In the present investigation the presence of Lf in gastric juice and its correlation with H. pylori infection were assessed. Methods: This study comprised 30 H. pylori-positive and 14 -negative patients with chronic gastritis. Gastric juice levels of Lf were measured with enzyme-linked immunoassays. Gastric juice concentration of Lf was also investigated in accordance with the histologic findings of biopsy specimens in the gastric body and antrum. Results: Lf concentration in gastric juice was significantly higher in H. pylori-positive than in -negative patients (P=0.033). The pH values are known to influence the levels of Lf. However, intragastric Lf levels were also significantly increased in H. pylori-positive ...

Cytotoxin genes of Helicobacter pylori in chronic gastritis, gastroduodenal ulcer and gastric cancer: an age and gender matched case-control study.

Abstract: Helicobacter pylori (H. pylori) infection is involved in many gastrointestinal diseases, such as chronic gastritis (CAG), peptic ulcer and gastric cancer (GCA). Both host factors and H. pylori strain differences may contribute to differences in the diseases. Thus, we conducted an age and gender matched case-control study of 35 patients each with CAG, gastric ulcer (GUL), duodenal ulcer (DUL) and gastric cancer (GCA) to examine the role of strain differences of the H. pylori cytotoxin genes cagA and vacA in these diseases. We employed polymerase chain reaction to examine the gastric juice for H. pylori DNA. The test was positive for 26 (74.3%) CAG, 29 (82.9%) GUL, 28 (80.0%) DUL and 27 (77.1%) GCA patients, showing no statistically significant difference among the diseases (P = 0.84). cagA and vacA genes (picked up by using a vacA1 + vacA2 primer pair which detected non-variable regions of the vacA gene) were detected by PCR in the H. pylori DNA-positive cases as follows: CAG, 92.3% and 76.9%; GUL, 100% and 86.2%; DUL, 89.3% and 89.3%; GCA, 92.6% and 85.2%, respectively. No statistically significant differences were found in the frequencies of these cytotoxin genes in H. pylori-positive cases among the various gastric diseases (P = 0.39 for cagA and P = 0.64 for vacA).

Mucosal chemokines in Helicobacter pylori infection.

Abstract: Chemokines are a family of low-molecular-weight proinflammatory cytokines that have leukocyte chemotactic and activating properties. Chemokine protein and mRNA are increased in the gastric mucosa of Helicobacter pylori infection and they are considered to regulate migration of leukocyte populations. The increase of C-X-C chemokines (e.g. IL-8, GRO-alpha) which effect primarily neutrophils is significantly associated with gastric polymorphonuclear cell activity suggesting that these chemokines play a primary role in active gastritis induced by H. pylori infection. In vitro enhanced epithelial chemokine responses are induced by cagA positive strains which have been clinically associated with more severe clinical outcome. Infection with cagA-positive H. pylori strains associates in vivo specifically with a C-X-C profile and enhanced polymorphonuclear infiltration in the gastric mucosa. Whilst infection with H. pylori, especially cag positive strains, is associated with more severe disease, genetic variability in host chemokine responses may also contribute to disease outcome.

Helicobacter pylori infection and coagulation in healthy people

Abstract: Helicobacter pylori infection has recently been associated with an increased risk of developing ischaemic heart disease.1 2 It has been suggested that chronic gastritis related to H pylori infection may increase, through inflammatory mediators, the concentration of certain coagulation factors such as fibrinogen,3 which are predictors of ischaemic heart disease.4 We investigated the potential association between H pylori infection and abnormalities of plasma coagulation in healthy people, with particular emphasis on the possibility of H pylori inducing a tendency towards coagulation, thereby influencing the risk of ischaemic heart disease. Initially, 368 consecutive asymptomatic blood donors (unpaid volunteers) were recruited for this study. Exclusion criteria were age >51 years, any chronic drug treatment, recent intake of drugs interfering with blood coagulation, use of oral contraceptives, previous treatment for H pylori infection, …

Gastric corpus IL‐8 concentration and neutrophil infiltration in duodenal ulcer patients

Abstract: Background: The purpose of the present study was to examine the association between interleukin-8 (IL-8) in the gastric body due to Helicobacter pylori infection and histological gastritis, as well as elucidating the effect of acid secretion inhibitors on H. pylori associated body gastritis in duodenal ulcer patients. Methods: Twenty H. pylori-negative patients, 20 H. pylori-positive patients with chronic gastritis without peptic ulceration, and 20 H. pylori-positive duodenal ulcer patients (DU) were studied. Four biopsy samples were taken, each from the greater curvature of the antrum and body of the stomach. Biopsies were histologically investigated by ELISA to determine the density of H. pylori, the degree of neutrophil infiltration and the IL-8 concentration in the mucosa. Results: In the gastric mucosa of H. pylori-negative subjects, no IL-8 and hardly any neutrophil infiltration were observed. In contrast, enhanced IL-8 production and increased neutrophil infiltration were present in those infected with H. pylori. In H. pylori-positive patients, a significant correlation was observed between the IL-8 concentration and the degree of neutrophil infiltration, but no correlation was found in the body mucosa of those with DU. Twelve of 20 DU patients demonstrated hardly any neutrophil infiltration, despite the increased mucosal IL-8 content in the body. The administration of omeprazole in DU patients markedly increased mucosal neutrophil infiltration even though it did not cause any significant change in the H. pylori density and IL-8 concentration in the body. Although the effect of omeprazole was transient, a significant increase in neutrophil infiltration continued in comparison with the status before omeprazole administration in those subsequently undergoing maintenance treatment with H2-blockers. Conclusion: In H. pylori-positive chronic gastritis, IL-8 concentration is enhanced in the mucosa of the body, and is associated with increased neutrophil infiltration. However, in DU patients, despite increases in body IL-8 concentration, neutrophil infiltration is reduced and the gastritis may be localized in the antrum.