Shigemi Nakajima

Mast cell involvement in gastritis with or without Helicobacter pylori infection

BACKGROUND & AIMS Mast cells are initiators and regulators of inflammation, but their role in the human stomach remains unclear. Therefore, the extent and distribution of mast cell involvement in gastritis with or without Helicobacter pylori infection was investigated. METHODS Mapped biopsy specimens from 17 H. pylori-positive and 20 H. pylori-negative subjects were examined. Sections were assessed for infection and inflammation and stained with anti-human mast cell tryptase to count mucosal and epithelial mast cells. Density of mast cells in different gastric compartments, their response to infection treatment, and their relationship with other inflammatory cells were evaluated. Mast cell degranulation was evaluated by electron microscopy. RESULTS Mast cell density was significantly greater in the mucosa with gastritis, with or without H. pylori infection, than in the mucosa of noninfected normal subjects. In the antrum, density was much greater in H. pylori-infected peptic ulcer subjects than in the other gastritis groups. It also correlated significantly with the intensity of inflammation. Mast cell degranulation was demonstrated by electron microscopy in H. pylori-infected mucosa. Mast cell density in ulcer patients decreased significantly after cure of H. pylori infection. CONCLUSIONS Mast cells may be important effector cells in the pathogenesis of gastritis, especially in H. pylori-associated peptic ulcer.

Changes in the prevalence of Helicobacter pylori infection and gastrointestinal diseases in the past 17 years.

Background and Aims:  The aim of the study was to examine whether the change in the prevalence of Helicobacter pylori infection had influenced upper gastrointestinal diseases in a recent 17‐year period.

The G-Protein β3 subunit 825 TT genotype is associated with epigastric pain syndrome-like dyspepsia

BackgroundAlthough familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well understood. Several reports indicate an association between FD and G-protein β3 (GNB3) subunit gene polymorphism (C825T); however, these studies had small sample sizes and the findings are inconclusive. In the present study we clarified the association between GNB3 gene polymorphism and dyspepsia in a large population of Japanese subjects who visited a hospital for annual health check-up.MethodsSubjects with significant upper gastrointestinal findings were excluded. Subjects with dyspeptic symptoms were divided into either a postprandial distress syndrome (PDS) group or an epigastric pain syndrome (EPS) group according to the Rome III criteria. The presence of the GNB3 C825T polymorphism was then evaluated and logistic regression analysis was used to test all variables.ResultsThe GNB3 genotype distribution in subjects without dyspepsia was 191 CC (25.1%), 368 TC (48.4%), and 202 TT (26.5%) and 17 CC (25.0%), 29 TC (42.6%), and 22 TT (32.4%) in subjects with dyspepsia. No significant correlation was found between the GNB3 825TT genotype and dyspepsia. However, the TT genotype was significantly associated with subjects with EPS-like symptoms (odds ratio (OR) = 2.00, 95% confidence interval (CI); 1.07-3.76) compared to the CT/CC genotype adjusted for gender and age. No significant correlation was found between GNB3 polymorphism and PDS-like symptoms (OR = 0.68, 95% CI; 0.31-1.51). With the exclusion of subjects with both EPS- and PDS-like symptoms, only the TT genotype was significantly associated with EPS-like symptoms (OR = 2.73, 95% CI; 1.23-5.91).ConclusionThe homozygous GNB3 825T allele influences the susceptibility to EPS-like dyspepsia.

Prevalence of Helicobacter pylori Infection by Birth Year and Geographic Area in Japan

Helicobacter pylori (H. pylori)‐related diseases are responsible for a tremendous amount of morbidity and mortality in Japan. We estimated the prevalence of H. pylori infection by sex, birth year, and geographic area among Japanese adults.

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.

Spectra of functional gastrointestinal disorders diagnosed by Rome III integrative questionnaire in a Japanese outpatient office and the impact of overlapping

Background and Aims:  The aim of this study was to establish the spectra of functional gastrointestinal disorders (FGID) in a Japanese outpatient office in Rome III.

Histological aspects and role of mast cells in Helicobacter pylori‐infected gastritis

Background : Mast cells are one of the main pro‐inflammatory cells, while their knowledge in Helicobacter pylori infection has not been summarized.

Serotonin transporter gene polymorphism may be associated with functional dyspepsia in a Japanese population

BackgroundAlthough familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well understood. In the present study, the association between serotonin transporter (SERT) gene (SLC6A4) polymorphism and FD was explored.MethodsSubjects were divided into either a postprandial distress syndrome (PDS) group or an epigastric pain syndrome (EPS) group according to the Rome III criteria. The healthy controls were those who had visited a hospital for an annual health check-up. The presence of the SLC6A4 promoter polymorphism, 5-hydroxytryptamin transporter gene linked polymorphic region (5-HTTLPR), was then evaluated, and logistic regression analysis was used to test all variables.ResultsThe 5-HTTLPR genotype distribution was 448 SS, 174 SL, and 24 LL in controls and 30 SS, 20 SL, and 3 LL in FD subjects. No significant correlation was found between the 5-HTTLPR genotype and FD. When the genotypes and subtypes of FD were exploratory evaluated, the SL genotype was significantly associated with PDS [odds ratio (OR) = 2.24, 95% confidence interval (CI); 1.16-4.32, P = 0.034 after Bonferroni correction] compared to the SS genotype adjusted for sex and age. Comparison of the SS genotype with the SL/LL genotype also showed a significant association of genotype with PDS (OR = 2.32, 95% CI; 1.23-4.37, P = 0.009).ConclusionThe present results suggest that 5-HTTLPR L allele may influence the susceptibility to PDS.

Genetic factors for functional dyspepsia.

Background:  Although familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well established. Several reports indicate the associations between FD and gene polymorphisms, however the data are inconsistent. This review summarized the evidence of genetics in FD based on genetic epidemiology.

Increase in mucosal and connective tissue-type mast cells in the stomach with acetic acid-induced ulcer in rat

Gastric ulcers were induced in rats by acetic acid treatment, and the mast cell kinetics in the lesions were studied. Within 24 h, mast cells had disappeared from the treated site and from the marginal zone, corresponding to the area of severe tissue injury. Regenerating epithelium appeared at day 10, and the lesion had healed by day 30. In this healing process, the number of mast cells was significantly increased, and their density in the regenerating mucosa, marginal mucosa, and marginal muscularis propria was 3.2 1.8, and 7.5‐fold the control level, respectively. The increase in the number of mast cells was preceded by an increase in the percentage of S‐phase mast cells. Mast cells in the mucosa were Alcian blue (AB)+/safranin (S)− and rat mast cell protease (RMCP) I−/II+, consistent with the features of mucosal mast cells throughout the observation period. On the other hand, most mast cells in the muscularis propria exhibited AB+/S+ and RMCP I+/II+ in the early period of ulcer healing. The latter feature was changed to RMCP I+/II− on day 30, indicating that immature CTMC appeared and then developed into mature CTMC during the ulcer healing. The significant change in the number of mast cells suggests that mast cells play an important role in the development and healing of gastric ulcers.