Histological Severity Of Gastritis Research Articles

Telomere length in non-neoplastic gastric mucosa and its relationship to H. pylori infection, degree of gastritis, and NSAID use.

Telomere shortening occurs with human aging in many organs and tissues and is accelerated by rapid cell turnover and oxidative injury. We measured average telomere length using quantitative real-time PCR in non-neoplastic gastric mucosa and assessed its relationship to H. pylori-related gastritis, DNA methylation, ulcer disease, and nonsteroidal anti-inflammatory drug (NSAID) usage. Gastric biopsies were obtained from 151 cancer-free subjects including 49 chronic NSAID users and 102 nonusers. Relative telomere length in genomic DNA was measured by real-time PCR. H. pylori infection status, histological severity of gastritis, and serum pepsinogens (PGs) were also investigated. E-cadherin (CDH1) methylation status was determined by methylation-specific PCR (MSP). Average relative telomere length of H. pylori-infected subjects was significantly shortened when compared to H. pylori-negative subjects (p = 0.002) and was closely associated with all histological parameter of gastritis (all p values <0.01) and CDH1 methylation (p = 0.0002). In H. pylori-negative subjects, NSAID users presented significantly shorter telomere length than nonusers (p = 0.028). Shorter telomere length was observed in duodenal and gastric ulcer patients compared with non-ulcer subjects among NSAID users. Telomere shortening is closely associated with severity of H. pylori-induced gastritis and CDH1 methylation status. Also, telomere shortening is accelerated by NSAID usage especially in H. pylori-negative subjects.

Impact of H. Pylori on Growth: Is the Infection or Mucosal Disease Related to Growth Impairment?

Helicobacter pylori (H. pylori) has been recognized as one of the most common chronic bacterial infections in the world. Most children are colonized in early childhood, and the infection will last a lifetime unless the child is treated with appropriate antibiotics. To evaluate whether H. pylori infection has an influence on growth and whether the severity of endoscopic findings relates to the growth impairment. We formed four groups based on the presence or absence of H. pylori infection and gastrointestinal complaints as follows: group I: RAP +/H. pylori+; group II: RAP +/H. pylori-; group III: RAP -/H. pylori+; group IV: RAP -/H. pylori-. The relationship between endoscopic appearances, histological severity of gastritis, and antral H. pylori density with growth parameters was evaluated. The BMI standard derivation scores of groups I and II were significantly lower than those of asymptomatic controls independent of their H. pylori status. A significant difference in height for age standard derivation scores was observed only between groups I and IV. When we compared the BMI and height for age standard derivation scores of group III and group IV combined with that of the endoscopically normal children in the recurrent abdominal pain group, there was no significant difference between the two groups. Recurrent abdominal pain associated with gastric mucosal injury plays a role in a decrease in BMI independent of H. pylori infection. However, if recurrent abdominal pain originates from H. pylori infection, it appears that linear growth is also affected.

Gastric Intestinal Metaplasia (GIM). Natural History and Surveillance

Purpose: Determine the prevalence of GIM in GI subspecialty patients, assess the diagnostic value of histological grading, including gastritis and presence of Helicobacter pylori (HP) relative to the risk of adenocarcinoma (GC) distal to the cardia. Methods: In the course of 19 years, there were 11,600 EGDs that diagnosed 354 male patients with GIM (one GIM in 33 EGDs). Of these, 185 patients had at least one follow-up EGD (53%) and 11% had four or more EGDs. The interval between the first and last EGD was 39.4 (34.5 SD) months (1-204). Results: Compared with 350 non-gastric randomly sampled GI controls, patients with GIM tended to be older, with 55.7% being over the age of 70. Fifty percent were African-American and 44.6% were Caucasian, almost identical with the controls. GIM was graded 1 - 5 with a mean grade of 2.2 on initial EGD in non GC patients, while in the 21 patients with GC (5.9% of all GIM cases), it was 4.8. Of the patients with GC, 67% were African-Americans, higher than their distribution among other GIM patients. GIM was labeled as focal in 58%, mild to moderate in 30%, extensive in 8% and malignant in 4%. Severity of GIM did not differ among the age groups, ethnic groups, 153 HP positive and 201 HP negative patients. Of 90 HP positive patients who had repeated EGD, HP was diagnosed only at the initial EGD in 56% (effect of therapy?). Histological severity of gastritis and the number of mucosal inflammatory nodules did not differ among the subgroups. Conclusion: GIM contributes to gastric cancer in a large segment of patients at risk. Patients older than 70 and African-Americans are at higher risk. HP and gastritis were not reliable predictors of neoplasia (therapy? sampling error?). Histologic grading of GIM is relatively non sensitive for staging and progression. Patients who are diagnosed with GIM for the first time should undergo endoscopic surveillance irrespective of the initial grade of GIM. There should be biopsies from multiple gastric sites to increase the diagnostic yield. A biomarker for GIM would increase the effectiveness of screening for gastric cancer.

Evaluation of a New Tumor Necrosis Factor‐α‐Inducing Membrane Protein of Helicobacter pylori as a Prophylactic Vaccine Antigen

Tumor necrosis factor (TNF)-alpha-inducing protein (Tip alpha) is a newly identified carcinogenic factor present in Helicobacter pylori. Tip alpha has the unique function of inducing TNF-alpha production by gastric cells in vitro and is assumed to be related with the development of gastritis and gastric cancer. We investigated the effects of vaccination with Tip alpha against H. pylori infection and analyzed the immune responses. C57BL/6 mice were immunized via the intranasal route with CpG, recombinant Tip alpha + CpG, and recombinant del-Tip alpha (a mutant of Tip alpha) + CpG. Eight weeks after the mice were infected with H. pylori (5 x 10(7) CFU), the number of colonizing bacteria in the stomach was calculated, and the histological severity of gastritis was evaluated. Levels of Tip alpha-specific IgG and IgA antibodies in mouse serum were measured by an enzyme-linked immunosorbent assay (ELISA). Local production of cytokines including Interleukin (IL)-10, TNF-alpha and Interferon (IFN)-gamma in gastric mucosa was also measured by real time-PCR. Levels of Tip alpha-specific antibodies were significantly higher in Tip alpha-immunized and del-Tip alpha-immunized mice than in the infection control group. The numbers of colonizing bacteria were significantly reduced in Tip alpha-immunized mice (4.29 x 10(5) CFU/g) and del-Tip alpha immunized mice (2.5 x 10(5 )CFU/g) compared with infection control mice (5.7 x 10(6) CFU/g). The levels of IFN-gamma and IL-10 were significantly higher in del-Tip alpha-immunized mice than the infection control group. Vaccinations with Tip alpha and del-Tip alpha were effective against H. pylori infection. The inhibition of H. pylori colonization is associated mainly with Th1 cell-mediated immunity.

&lt;i&gt;Helicobacter pylori&lt;/i&gt; Infection and Strain Types in Adult Dyspeptic Patients Undergoing Endoscopy in a Specialized Hospital of Dhaka City

Helicobacter pylori infection occurs worldwide with a high prevalence in developing countries. Virulence of H. pylori strains varies in different geographic regions. The aim of this study was to see H. pylori infection and its strain types in adult dyspeptic patients in Bangladesh and to analyze association of H. pylori strain types with clinical disease and severity of histological gastritis. Ninety consecutive adult dyspeptic patients undergoing diagnostic endoscopy were tested for H. pylori infection by culture, rapid urease test (RUT), histology and anti H. pylori IgG ELISA (Enzyme linked immunosorbent assay). H. pylori strain types were determined by Western Blot analysis. Association of strain types with clinical gastro-duodenal diseases and grades of histological gastritis were analyzed by χ2 test. Among the selected patients, 53 (58.9%) were culture positive, 48 (53.3%) were RUT positive, 31 (34.4%) were histology positive and 82 (91.1%) were anti-H. pylori IgG ELISA positive. By Western Blot analysis of the 90 sera samples, 48 (53.3%) showed antibodies to Type I strain of H. pylori, 21 (23.3%) Intermediate strain and 3 (3.3%) Type II strain. Endoscopically, 20 (22.2%) patients were found normal, 27 (30.0%) had gastritis, 9 (10.0%) had duodenitis, 28 (31.1%) had peptic ulcer disease, 4 (4.4%) had gastric carcinoma, and 2 (2.2%) had reflux esophagitis. Histologically, 34.4% had H. pylori, 44.4% had polymorhonuclear neutrophil (PMN), 100% had mononuclear cell (MNC) infiltration of different grades, 1.1% had atrophic gastritis and 2.2% had intestinal metaplasia of moderate grade. H. pylori strain types was not associated with clinical gastro-duodenal diseases or grades of PMN or MNC infiltration (p &gt; 0.05) in these patients. Key words: Helicobacter pylori infection, H. pylori strain types, gastro-duodenal diseases, grades of gastritis doi: 10.3329/bjmm.v3i1.2963 Bangladesh J Med Microbiol 2009; 03 (01): 4-9

Gastric mucosal pattern by using magnifying narrow-band imaging endoscopy clearly distinguishes histological and serological severity of chronic gastritis

Magnifying narrow-band imaging (NBI) endoscopy clearly visualizes superficial gastric mucosal patterns and capillary patterns. To investigate gastric mucosal patterns by using magnifying NBI endoscopy and identify any relationship between those patterns and Helicobacter pylori-induced gastritis. Gastric mucosal patterns seen with magnifying NBI in uninvolved gastric corpus were divided into the following categories: normal--small, round pits with regular subepithelial capillary networks; type 1-slightly enlarged, round pits with unclear or irregular subepithelial capillary networks; type 2--obviously enlarged, oval or prolonged pits with increased density of irregular vessels; and type 3-well--demarcated oval or tubulovillous pits with clearly visible coiled or wavy vessels. Department of Gastroenterology, Fujita Health University. This study involved 106 participants undergoing upper endoscopy. H pylori infection-positive ratios of normal and types 1, 2, and 3 patterns were 7.5%, 92.9%, 94.5%, and 66.7%, respectively. Sensitivity and specificity for types 1 + 2 + 3 for detection of H pylori positivity and type 3 for detection of intestinal metaplasia were 95.2%, 82.2%, 73.3%, and 95.6%, respectively. Development of mucosal patterns from normal to types 1, 2, and 3 was correlated with all histological parameters (P < .0001), lower pepsinogen I/II ratios (P < .0001), and degree of endoscopic atrophy (P < .0001). Sensitivity and specificity of type 3 for the prediction of severe histological atrophy was also better than those of serum pepsinogen level and standard endoscopy. Only 1 endoscopist performed endoscopic procedures, and interobserver agreement could not be assessed. Magnifying NBI endoscopy is useful for predicting H pylori infection and the histological severity of gastritis and is valuable for predicting gastric atrophy in the entire stomach.

Association of endoscopic appearances with dyspeptic symptoms

The relationship between endoscopic appearances such as endoscopic gastritis and duodenitis and dyspeptic symptoms has not been clearly demonstrated. We aimed to clarify the association of endoscopic appearances with Helicobacter pylori infection, histological severity of gastritis, and dyspeptic symptoms in a Japanese population. We enrolled 87 dyspeptic and 93 nondyspeptic subjects in this study. All subjects underwent gastroscopy, and patients with active peptic ulcer disease, reflex esophagitis with erosion, polyps >1 cm, or cancer were excluded. Endoscopic appearances in patients with dyspeptic symptoms and in those without were assessed retrospectively on the basis of endoscopic images. The degree of atrophy by the Kimura-Takemoto classification system was also assessed. Helicobacter pylori infection status was examined by histology or antibody against H. pylori. Histological severity of inflammation and glandular atrophy in the antrum were assessed according to the updated Sydney System. The odds ratio (OR) and 95% confidence interval (CI) were calculated by logistic regression using the variables age, sex, H. pylori infection status, and all endoscopic appearances. The degree of atrophy tended to be lower among dyspeptic patients (P = 0.06). Among all endoscopic appearances, the liner redness (friability) in the antrum (OR = 3.90, 95% CI = 1.20-12.64) and duodenal ulcer (DU) scarring (OR = 3.41, 95% CI = 1.08-10.79) were independently associated with dyspepsia. Histological severity of inflammation and glandular atrophy were not associated with dyspeptic symptoms. Also, no correlation was found between endoscopic appearances and any of the different subgroups of dyspeptic symptoms. Patients with friability in the antrum and DU scar, which correlated with dyspeptic symptom showed some of communal symptoms such as epigastric pain, epigastric discomfort, hypochondriac pain, early satiation/postprandial fullness, and belching, but they differed considerably with respect to H. pylori positivity and the histological severity of gastritis. Some endoscopic appearances such as friability in the antrum and DU scarring may be associated with dyspeptic symptoms, and endoscopic appearances may be useful markers to perform clinical implementation reflecting an individual's pathophysiology of dyspeptic symptoms.

Long-term effects of Helicobacter pylori eradication on circulating ghrelin and leptin concentrations and body composition in prepubertal children

Helicobacter pylori, and the chronic gastric inflammation that it causes, may compromise the function and survival of ghrelin-producing cells, resulting in a decrease of circulating ghrelin levels. This finding raises the possibility that the infection might affect growth in children by reducing the ghrelin production. To determine baseline circulating levels of ghrelin and leptin in prepubertal children with and without H. pylori infection and to evaluate the long-term effects of H. pylori eradication on circulating levels of ghrelin and leptin as well as on body composition. Thirty children with H. pylori-associated gastritis, 35 children with H. pylori-negative gastric mucosa, and 20 healthy controls were studied. At baseline, while leptin levels were significantly lower in H. pylori-positive patients, ghrelin concentrations did not differ among the three study groups. However, a significant inverse correlation between ghrelin concentrations and histological severity of gastritis was found. Eradication of the organism was associated with a progressive decrease in ghrelin concentrations over baseline at both 6- and 12-month follow-ups. SDS-body mass index (BMI), lean and fat mass, as well as leptin concentrations, significantly increased over baseline at both follow-ups. In prepubertal children, serum ghrelin concentrations are inversely related to the severity of H. pylori-associated gastritis. In these youngsters, long-term eradication of H. pylori infection is associated with a significant increase in BMI, lean and fat mass along with a significant decrease in circulating ghrelin levels and an increase in leptin levels.

Mast cell density in gastric biopsies of pediatric age group and its relation to inflammation and presence of Helicobacter pylori

BackgroundThe aim of this study was to investigate the relationship between mast cell density, histological severity of gastritis, and presence of Helicobacter pylori (H. pylori) in the antral mucosa of pediatric patients.MethodsThe study included 352 (192 male and 160 female, < 14 years old) patients. All cases underwent endoscopy, and biopsies were obtained for histopathological examination and evaluation of Helicobacter pylori. All biopsies were evaluated according to the Sydney system and mast cell density in the antral mucosa was analyzed by Giemsa stain. Spearman's correlation test was used to determine the relationship between mast cell density and other histopathological parameters. The comparison of mast cell density between H. pylori positive and negative groups was analyzed by Mann Whitney U test.ResultsMast cell density was 12.6 ± 0.87 in 0.25 mm2 (0–81). Means of severity of gastric inflammation in H. pylori-positive and negative patients were 1.7 ± 0.6 and 0.6 ± 0.7, respectively, which was statistically significant (p = 0.0001). Mast cell density was not correlated with presence and degree of inflammation, activity, presence and score of H. pylori in the antrum (p > 0.05). There was no significant correlation between mast cell density and allergy.DiscussionWe concluded that there may be some other ways for contribution of mast cells in pathologic processes involving gastrointestinal tract in children.

Interaction between Helicobacter pylori and immune response to CagA: CagA antibody may down‐regulate bacterial colonization and tyrosine phosphorylation

SummaryBackgroundCagA+Helicobacter pylori strains are associated with the development of gastroduodenal diseases. H. pylori possess a type IV secretion system that is responsible for the translocation of CagA into host cells.AimTo investigate the correlation between the CagA status and the severity of histological gastritis and to analyse the tyrosine phosphorylation of CagA.MethodsA total of 149 H. pylori status was determined via urine antibody to H. pylori, histological examination and serum antibody against CagA. Histological gastritis was evaluated using the updated Sydney system and scored from 0 to 3. Tyrosine phosphorylation was analysed using immunoprecipitation and immunoblotting.ResultsAnti‐CagA titres were correlated with the severity of mononuclear cell infiltration. In contrast, mean anti‐CagA in patients with grade 2 bacterial density was significantly higher than those with grade 0 (P &lt; 0.01). Mean anti‐titre in patients with grade 3 tended to be lower than that seen with grade 2. CagA tyrosine phosphorylation was significantly more common in bacteria isolated from CagA‐antibody‐negative patients (93%;13/14) than from CagA‐antibody‐positive patients (29%; 4/14, P = 0.0007).ConclusionsHost–bacteria interaction is regarded as one of the important factors in the development of gastroduodenal diseases.

Interaction between Helicobacter pylori and immune response to CagA: CagA antibody may down‐regulate bacterial colonization and tyrosine phosphorylation

SummaryBackgroundCagA+Helicobacter pylori strains are associated with the development of gastroduodenal diseases. H. pylori possess a type IV secretion system that is responsible for the translocation of CagA into host cells.AimTo investigate the correlation between the CagA status and the severity of histological gastritis and to analyse the tyrosine phosphorylation of CagA.MethodsA total of 149 H. pylori status was determined via urine antibody to H. pylori, histological examination and serum antibody against CagA. Histological gastritis was evaluated using the updated Sydney system and scored from 0 to 3. Tyrosine phosphorylation was analysed using immunoprecipitation and immunoblotting.ResultsAnti‐CagA titres were correlated with the severity of mononuclear cell infiltration. In contrast, mean anti‐CagA in patients with grade 2 bacterial density was significantly higher than those with grade 0 (P &lt; 0.01). Mean anti‐titre in patients with grade 3 tended to be lower than that seen with grade 2. CagA tyrosine phosphorylation was significantly more common in bacteria isolated from CagA‐antibody‐negative patients (93%;13/14) than from CagA‐antibody‐positive patients (29%; 4/14, P = 0.0007).ConclusionsHost–bacteria interaction is regarded as one of the important factors in the development of gastroduodenal diseases.

Relationship of TT virus and Helicobacter pylori infections in gastric tissues of patients with gastritis.

Blood and gastric tissue biopsies of 34 patients with gastritis were tested for the presence of TT virus (TTV), a ubiquitous virus found in the blood of most humans. Thirty-one of these patients were TTV positive, and 27 patients had virus in both tissues. In addition, 13 of the patients who had TTV in gastric tissue were Helicobacter pylori positive. There was an association of higher TTV titers in gastric tissues of patients who were H. pylori positive than in those in whom the bacterium could not be detected. Furthermore, this association was stronger in H. pylori-positive patients with the presence of the cagA protein. Of 10 specimens in which genogroup determination was carried out in the gastric corpus, 5/5 that were H. pylori positive showed the presence of TTV genogroup 3, while for those that were H. pylori negative, 5/5 showed the presence of genogroup 1t. By contrast, genogroup 1 was found in the corpus of only one H. pylori-positive patient, and genogroup 3 in only one H. pylori-negative patient. The histological severity of gastritis did correlate significantly with loads in the gastric tissues. There was no significant difference in TTV titer in blood of patients regardless of H. pylori infection status. These findings pique interest in clarifying the role of TTV, alone or in association with H. pylori infection, in the pathogenesis of gastritis.

Serum antibody against Helicobacter pylori assayed by a new capture ELISA.

We developed a highly specific detection technique for serum antibody, using a monoclonal antibody to a specific antigen of Helicobacter pylori. A monoclonal antibody preparation that reacted with the 54-kDa molecule of H. pylori antigens was obtained. Using this preparation, an antigen-capture enzyme-linked immunosorbent assay (ELISA) was established by fixation of the monoclonal antibody, followed by reaction with sonicated whole cell antigens. The serum antibody titers of patients with gastritis and peptic ulcers were significantly higher than control titers, and the antibody titer correlated with the histological severity of gastritis. Patients positive for H. pylori by bacterial culture had higher titers than H. pylori-negative patients. Our new ELISA may be useful for the diagnosis of H. pylori infections and for evaluation of the severity of gastric inflammation.

Effect of Helicobacter mustelae infection on ferret gastric epithelial cell proliferation.

The effect of Helicobacter mustelae infection on gastric epithelial proliferation was studied in ferrets colonized with H.mustelae and specific pathogen-free (SPF) ferrets not infected with H.mustelae. Thirteen H. mustelae-infected ferrets between the ages of 13 and 32 months and 16 SPF ferrets between 6 and 18 months were analyzed. Bacterial cultures, urease tests and Warthin-Starry stains were used to identify H.mustelae. Tissues obtained from the antrum and the body regions of the stomach were assayed by proliferating cell nuclear antigen (PCNA) immunohistochemistry and measured using a computerized color image analysis system. PCNA-expressing gastric epithelia in the antrum and the body regions were significantly increased in the H.mustelae-infected ferrets versus the SPF ferrets (P < 0.001). PCNA positivity in the antrum regions of both the H.mustelae-infected ferrets and SPF ferrets was significantly higher than that of the body regions (P < 0.001). Comparison of the histopathology of infected ferrets indicated that PCNA positivity correlated with the histological severity of gastritis. This study suggests that cell proliferation in ferret gastric mucosa increases with H.mustelae infection and provides evidence that PCNA is a useful biomarker for studying the changes in cell kinetics in the ferret stomach. The data also further support the use of the H.mustelae-infected ferret as an animal model for studying the pathogenesis of Helicobacter pylori-induced gastric diseases of humans.