Approximately 50% of Helicobacter pylori strains produce a cytotoxin that is encoded by vacA and that induces vacuolation of eukaryotic cells. Mosaicism in vacA alleles was reported, and there are three different families of vacA signal sequences (s1a, s1b, and s2) and two different families of middle-region alleles (m1 and m2). In addition, the vacA genotype of a strain is associated with its cytotoxin phenotype and its capacity to induce peptic ulceration. To clarify the strain diversity of H. pylori in Japan, 87 Japanese clinical isolates of H. pylori (40 from patients with chronic atrophic gastritis, 25 from patients with duodenal ulcer, 16 from patients with gastric ulcer, 3 from patients with both duodenal and gastric ulcers, and 3 from patients with intestinal type gastric cancer) were characterized by vacA typing by PCR and DNA sequencing. Eighty-four of the 87 isolates were s1a/m1, one was s1b/m1, and two could not be typed. Moreover, all isolates in this study were cagA positive. There were no distinct differences between the cytotoxin-producing strains and cytotoxin-nonproducing strains within the 0.73-kb middle region. Japanese strains were highly homologous, with more than 96% identity in this region, in which maximum divergence has been reported. In addition, there were no associations between the specific vacA types and the level of in vitro cytotoxin activity or the clinical consequences. These results indicate that the cagA-positive, s1a/m1-type strains are common in Japan, regardless of the vacA phenotype or clinical outcome.
Objective We assessed the factors associated with overlap between functional dyspepsia (FD) and nonerosive reflux disease (NERD) in endoscopy-based Helicobacter pylori-uninfected Japanese health checkup participants. Methods We utilized baseline data from 3,085 individuals who underwent upper endoscopy for health screening in a prospective, multicenter cohort study. The participants were asked to complete a questionnaire detailing their upper abdominal symptoms and lifestyle. Anxiety was assessed using the State-Trait Anxiety Inventory (STAI) score. FD, postprandial distress syndrome (PDS), and epigastric pain syndrome (EPS) were defined according to the Rome III criteria. NERD was defined as heartburn or regurgitation ≥1 day/week without erosive esophagitis. Results Of the 3,085 participants, 73 (2.4%), 97 (3.1%), and 84 (2.7%) had FD alone, NERD alone, and FD-NERD overlap, respectively. Factors associated with FD-NERD-overlap participants compared with participants with neither FD nor NERD were women [odds ratio (OR): 2.08, 95% confidence interval (CI): 1.24-3.52], body mass index (BMI) <18.5 (OR: 2.87, 95% CI: 1.56-5.07), alcohol consumption ≥20 g/day (OR: 1.85, 95% CI: 1.06-3.15), and a high STAI score (OR: 2.53, 95% CI: 1.62-4.00). Increasing age (OR: 1.06, 95% CI: 1.01-1.11) and EPS symptoms [pure EPS (OR: 3.67, 95% CI: 1.65-8.51) and PDS-EPS overlap (OR: 11.6, 95% CI: 4.09-37.2)] were associated with FD-NERD overlap vs. FD alone. Women (OR: 3.17, 95% CI: 1.47-7.04), BMI <18.5 (OR: 3.03, 95% CI: 1.04-9.90), and acid reflux symptoms ≥2 days a week (OR: 3.57, 95% CI: 1.83-7.14) were associated with FD-NERD overlap vs. NERD alone. Conclusion Understanding the clinical features of overlap between FD and NERD will lead to better management.
ABSTRACT Colonization of the stomach mucosa by Helicobacter pylori is a major cause of acute and chronic gastric pathologies in humans. Several H. pylori virulence genes that may play a role in its pathogenicity have been identified. The most important determinants are vacA and cagA in the cag pathogenicity island ( cag PAI) genes. In the present study, to consider the association of molecular genetics between vacA and the cag PAI regarding clinical outcome, we selected H. pylori strains with various genotypes of vacA in Japan and sequenced full-length vacA , cagA , and cagE genes. Sequencing of vacA and cagA genes revealed variable size, whereas the cagE gene was well conserved among strains. Each of the phylogenetic trees based on the deduced amino acid sequences of VacA, CagA, and CagE indicated that all three proteins were divided into two major groups, a Western group and an East Asian group, and the distributions of isolates exhibited similar patterns among the three proteins. The strains with s2 and s1a/m1a vacA genotypes and the Western-type 3′ region cagA genotype were classified into the Western group, and the strains with the s1c/m1b vacA genotype and the East Asian-type 3′ cagA genotype were included in the East Asian group. In addition, the prevalence of infection with the Western group strain was significantly higher in patients with peptic ulcer (90.0%, 9/10) than in patients with chronic gastritis (22.7%, 5/22) (χ2 = 12.64, P = 0.00057). These data suggest that the molecular genetics of vacA and cag PAI are associated and that the Western group with vacA and cag PAI genes is associated with peptic ulcer disease.
BACKGROUND AND AIM: To clarify the roles of Helicobacter pylori cytotoxin in gastric atrophy, the cytotoxin positive rate and cytotoxin activity in Fukui and Okinawa, where the prevalence of atrophic gastritis and gastric cancer risk are quite different, were studied. MATERIALS: Seventy three strains from Fukui and 51 from Okinawa were examined. METHODS: The validation of atrophy was done by endoscopy, being confirmed with histology. The supernatant of liquid H pylori culture media was concentrated 20-fold, serially diluted, using doubling dilutions, and scored from 1 to 8. The semi-quantitated cytotoxin activity was expressed as the maximum dilution score yielding > 50% A431 cell vacuolation, being standardised with bacterial density. RESULTS: The cytotoxin activity of the strains from Fukui was highly diverse compared with that from Okinawa, although the cytotoxin positive rate was not different. In Fukui strains, the grade of atrophy and the cytotoxin activity were correlated (p < 0.05). In addition, the cytotoxin activity of the strains from all patients in Okinawa, most of whom showed closed-type/mild atrophy, was significantly lower than that of the strains from the patients with open-type/severe atrophy in Fukui (6.46 (5.53) v 9.76 (8.80), p < 0.05), (mean (SEM)). CONCLUSION: The difference in profile of the cytotoxin activity in the two areas was related to the difference in the prevalence of atrophic gastritis.
Polymorphisms of the 5′‐flanking promoter/enhancer region of the TNFA gene were determined in 80 Japanese patients with pulmoplantar pustulosis (PPP). The 5′‐flanking region of the TNFA gene from –1107 to –66 was amplified by polymerase chain reaction (PCR) method. Nucleotide sequencing data from the PCR products revealed that 5 single nucleotide polymorphisms at position –1031, –863, –857, –307 and –237. None of the nucleotide substitutions were significantly increased in PPP patients when compared with those in controls. To clarify the linkage among the neighboring genetic marker, we analyzed the association between the polymorphisms in the TNFA promoter region and the Nco I polymorphism in the first intron of the TNFB gene as well as HLA‐DR9 . The genotype at –1031C is strongly associated with TNFB1 and negatively associated with TNFB2 which is reported to be associated with PPP. These data indicate that TNFA gene centromeric to TNFB is not associated with PPP and the susceptible gene of PPP is located between TNFB and HLA‐B .
Abstract: In animals a continuous administration of 0.02% NH 3 induced by Helicobacter pylori is well known to lead to glandular atrophy of the gastric mucosa and to induce active, chronic gastritis. In addition, this organism has been demonstrated to be closely related to chronic, active gastritis in man. In the present study, a phenol red dye spraying endoscopy was re‐formed in 54 patients with chronic, atrophic gastritis to elucidate the distribution of this organism in the human gastric mucosa, and to clarify the relationship between its presence and chronic, atrophic gastritis. No red color reaction was found in 12 (92.3%) of 13 patients who had no glandular atrophy of the stomach. A diffuse and/or regional red color reaction was most prominent in those with slight degrees of glandular atrophy of the stomach, and was less striking in those with severe atrophy of the gastric mucosa associated with intestinal metaplasia. In addition, no red color reaction was visible in 14 (87.5%) of 16 patients showing a C 0 pattern in the fundic‐pyloric border classification, whereas a diffuse and/or regional red color reaction was observed in over 75% of patients showing C 1 ‐O 2 patterns and less frequently in those with an O 3 Pattern. These data suggest a positive relationship between the presence of this organism and chronic, atrophic gastritis in man.
Upper gastrointestinal symptoms (UGSs), including reflux and dyspeptic symptoms (postprandial distress syndrome [PDS] and epigastric pain syndrome [EPS]), affect health-related quality of life. However, the influence of sex on the relationship between body mass index (BMI) and UGSs remains controversial. This study investigates the influence of sex on this association in healthy subjects.We utilized the database of a prospective, multicenter, cohort study of 7112 subjects who underwent upper endoscopy for health screening. A multivariable logistic regression analysis was conducted to assess the association between BMI and UGSs stratified by sex, adjusting for clinical features. The influence of sex on the association between the overlapping of UGSs and BMI in symptomatic subjects was also investigated. Reflux symptoms were significantly associated with high BMI (multivariable odds ratio [OR] 1.36; 95% confidence interval [CI] 1.10-1.67, P = 0.004). PDS symptoms were significantly associated with low BMI (OR 2.37; 95% CI 1.70-3.25; P < 0.0001), but EPS symptoms were not associated with BMI. The association between reflux symptoms and higher BMI was limited to men (men: OR 1.40; 95% CI 1.10-1.77; P = 0.005, women: P = 0.40). sex did not influence the association between the presence of PDS symptoms and lower BMI. The percentage of overlapping of all three symptoms (reflux, PDS, and EPS) was higher in women than in men (19.9% [58/292] vs 10.5% [49/468], P = 0.0002).The influence of BMI on the presence of UGSs was significantly different according to sex in this large-scale cohort.
