Tadashi Shimoyama

High Prevalence of the CagA-positive Helicobacter pylori Strains in Japanese Asymptomatic Patients and Gastric Cancer Patients

BACKGROUND Several studies have shown that infection of Helicobacter pylori strains possessing cagA is associated with atrophic gastritis and gastric cancers. METHOD In 58 pairs of early gastric cancer patients and sex- and age-matched controls, isolated H. pylori strains were tested for possession of cagA. The presence of atrophic gastritis was also examined. RESULTS Proportions of cagA-positive strains were 100% in cancer patients and 92.3% in controls. Atrophic gastritis was seen in 96.7% and 95.8% of cancer and control patients in whom cagA-positive strains (NS) were detected. However, it was seen in only 20% of H. pylori-negative control patients (P < 0.01). CONCLUSIONS The present results do not suggest any specific association between cagA-positive strains and gastric cancer. However, frequent prevalence of cagA-positive strains might be associated with the high incidence of atrophic gastritis in Japanese populations.

CagA seropositivity associated with development of gastric cancer in a Japanese population.

BACKGROUND/AIMS: Infection with Helicobacter pylori strains possessing the cagA gene is associated with increased risk of gastric cancer of the intestinal type. The aims of this study were to investigate whether CagA seropositivity is associated with increasing risk of gastric cancer in a Japanese population that has a much higher incidence of gastric cancer than western populations. METHODS: Eighty one gastric cancer patients and 81 sex and age matched endoscopically evaluated controls were studied. Histologically, 62 cancers were of the intestinal type and 76 were early gastric cancer. Serum CagA IgG antibodies were assayed by enzyme linked immunosorbent assay (ELISA) using purified recombinant CagA protein as antigen. Polymerase chain reaction (PCR) analysis for cagA in H pylori isolates (n = 80) showed that the CagA ELISA had a sensitivity of 83.3% (controls) and 72.5% (cancers). RESULTS: CagA seropositivity was 60% (49 of 81) in cancer patients and 44% (36 of 81) in controls. The odds ratio for the risk of cancer if CagA seropositive was 1.93 (95% confidence interval (CI) 1.01 to 3.68; p < 0.05). In the 57 H pylori positive cancer patients and their matched H pylori positive controls, the odds ratio for the risk of cancer if CagA seropositive was 2.2 (95% CI 1.04 to 4.65; p < 0.05). CONCLUSIONS: These results suggest that CagA seropositivity is associated with increased risk of gastric cancer in Japanese populations.

Low-level laser irradiation attenuates production of reactive oxygen species by human neutrophils.

OBJECTIVE The aim of this study was to examine the effects of low-level laser therapy (LLLT) on production of reactive oxygen (ROS) species by human neutrophils. BACKGROUND DATA LLLT is an effective therapeutic modality for inflammatory conditions. MATERIALS AND METHODS The laser device used was the infrared diode laser (GaAlAs), 830-nm continuous wave (150 mW/cm(2)). After irradiation, ROS production by neutrophils was measured using luminol-dependent chemiluminescence (LmCL) and expression of CD11b and CD16 on neutrophil surface was measured by flow cytometry. RESULTS The LmCL response of neutrophils was reduced by laser irradiation at 60 min prior to the stimulation with opsonized zymosan and calcium ionophore. The attenuating effect of LLLT was larger in neutrophils of smokers than non-smokers, while the amount of produced ROS was larger in neutrophils of smokers. Expression of CD11b and CD16 on neutrophil surface was not affected by LLLT. CONCLUSION Attenuation of ROS production by neutrophils may play a role in the effects of LLLT in the treatment of inflammatory tissues. There is a possible usage of LLLT to improve wound healing in smokers.

Effect of Helicobacter pylori eradication in the treatment of Japanese patients with chronic idiopathic urticaria

BackgroundInfection with Helicobacter pylori has been associated with chronic idiopathic urticaria (CIU). The aim of this study was to investigate the efficacy of H. pylori eradication in the treatment of patients with CIU.MethodsFifty patients with CIU (16 men and 34 women; age 25–75 years) and 100 sex- and age-matched control subjects were enrolled in the study. Presence of IgG antibody to H. pylori was examined by serology. H. pylori-seropositive patients with CIU received endoscopy to confirm H. pylori infection. Patients infected with H. pylori received eradication therapy comprising lansoprazole, amoxicillin, and either clarithromycin or metronidazole. At least 2 months after finishing the eradication therapy, a 13C-urea breath test was performed, and the effect of eradication therapy on the CIU was scored, using a three-point scale, as complete remission, partial remission, or no improvement.ResultsIn the 50 patients with CIU, 26 (52%) were H. pylori-seropositive, while 48% (48/100) of the control subjects were seropositive (statistically not significant). Nineteen out of the 26 patients with CIU infected with H. pylori received eradication therapy, and eradication was successful in 17 patients. In the 17 H. pylori-eradicated patients, 6 (35%) had complete remission and 11 (65%) had complete remission or partial remission. On the other hand, in the 9 patients without H. pylori eradication, only 2 (22%) showed partial remission and 7 (78%) had no improvement.ConclusionsEradication of H. pylori would be a valid choice for patients with CIU, although the prevalence of H. pylori infection is not higher in patients with CIU than it is in controls.

Exercise training and energy restriction decrease neutrophil phagocytic activity in judoists.

PURPOSE To investigate the effects of weight reduction as the result of exercise training and energy restriction on neutrophil function. METHODS Eighteen male competitive college judoists participated in the study. In a whole blood assay, oxidative burst activity, phagocytic activity, expressions of Fc gamma receptor 3 (CD16), and complement receptor 3 (CD11b) of neutrophils were measured on a per cell basis by flow cytometry at day 20, 5, and 1 before and at day 7 after the competition. RESULTS The rate of neutrophil producing reactive oxygen species decreased before the competition, whereas the oxidative burst activity per cell increased significantly in all subjects, which resulted in a significant increase of the total oxidative burst activity. However, there were no significant effect of energy restriction on oxidative burst activity. The rate of neutrophils incorporating opsonized zymosan decreased significantly with energy restriction. The total phagocytic activity of 10,000 neutrophils and the phagocytic activity per cell also decreased significantly by severe energy restriction. The surface antigen expressions of CD11b and CD16 were unaffected by weight reduction. CONCLUSIONS The results suggest that with respect to the management of health conditions, weight reduction for judoists should be composed of exercise training and energy restriction should be moderate.

Adverse effects of energy restriction on myogenic enzymes in judoists

In this study, we examined the effects of weight reduction by restricting energy intake on muscle function and serum concentrations of myogenic enzymes in judoists. Twenty-seven male judoists aged 19.3±0.6 years (mean±s) were divided into three groups based on the extent of body weight reduction: high weight reduction (height 1.70±0.05 m, body mass 78.5 ±13.6 kg), low weight reduction (height 1.70±0.05 m, body mass 80.7±13.1 kg) and a group that maintained body weight while continuing to perform exercise training (height 1.78± 0.07 m, body mass 78.7±8.8 kg). Body composition, blood biochemistry, energy intake and anaerobic power were assessed on four occasions: 20 days (baseline data), 4 days and 1 day before and 7 days after competition. Compared with baseline, body mass and fat-free mass were significantly lower 1 day before competition in the high and low weight reduction groups (both P <0.01); these changes persisted for 7 days after competition in the high weight reduction group. Serum creatine kinase was significantly elevated 1 day before competition in all groups (all P <0.05), and remained higher 7 days after competition in both the high and low weight reduction groups. Compared with baseline, maximal anaerobic power was significantly lower 1 day before competition only in the high weight reduction group (P <0.01). Our results suggest that energy restriction in addition to intense exercise training before major competition has an adverse effect on anaerobic power and elevates serum creatine kinase concentration, leading to an impairment of muscular function and an increased susceptibility of muscle tissue to injury.

Spatial distribution and histogenesis of colorectal Paneth cell metaplasia in idiopathic inflammatory bowel disease

Background and Aim: Colorectal Paneth cell metaplasia (PCM) is known to be a sign of idiopathic inflammatory bowel disease (IBD), although its distribution and histogenesis are not fully understood. Objectives of this research were to investigate the spatial distribution of PCM in IBD and other forms of colitis (non‐IBD), and to find stimuli causing PCM.

Effect of sodium butyrate on reactive oxygen species generation by human neutrophils.

BACKGROUND Short-chain fatty acids enema has been shown to be effective in the treatment of ulcerative colitis (UC). However, the mechanisms that lead to this response have not been well characterized. The aims of this study were to investigate the effect sodium butyrate has on reactive oxygen species (ROS) generation by human neutrophils, which are responsible for mucosal injury. METHODS Human neutrophils incubated with or without sodium butyrate were stimulated with opsonized zymosan (OZ) or phorbol myristate acetate (PMA). ROS generation was largely differentiated with flow cytometry assays of hydroethidine oxidation and dichlorofluorescein oxidation for superoxide anion and hydrogen peroxide respectively, and luminol-dependent chemiluminescence for myeloperoxidase-mediated oxidants. RESULTS Sodium butyrate (up to 50 mM) did not alter hydroethidine oxidation upon stimulation of the OZ or PMA. However, sodium butyrate at a concentration of 25 mM elevated dichlorofluorescein oxidation to 125 + 8% (P = 0.028) of control upon stimulation of OZ and to 191 +/- 30% (P = 0.0016) upon stimulation of PMA. Contrary to these results, sodium butyrate greatly inhibited chemiluminescence responses in a dose-dependent manner. The inhibition by 50 mM sodium butyrate was 61 +/- 6% upon OZ and 71 +/- 9% upon PMA, respectively. CONCLUSIONS These data indicate that sodium butyrate up-regulates hydrogen peroxide generation but down-regulates generation of myeloperoxidase-mediated oxidants, the latter being more potent in killing microorganisms and in inducing tissue injury. A possible mechanism is suggested whereby sodium butyrate may inhibit myeloperoxidase activity and hence attenuate the destructive activities of neutrophils in UC.Background: Short-chain fatty acids enema has been shown to be effective in the treatment of ulcerative colitis (UC). However, the mechanisms that lead to this response have not been well characterized. The aims of this study were to investigate the effect sodium butyrate has on reactive oxygen species (ROS) generation by human neutrophils, which are responsible for mucosal injury. Methods: Human neutrophils incubated with or without sodium butyrate were stimulated with opsonized zymosan (OZ) or phorbol myristate acetate (PMA). ROS generation was largely differentiated with flow cytometry assays of hydroethidine oxidation and dichlorofluorescein oxidation for superoxide anion and hydrogen peroxide respectively, and luminol-dependent chemiluminescence for myeloperoxidase-mediated oxidants. Results:

Cyclooxygenase-2 expression is increased in early intestinal-type gastric cancer and gastric mucosa with intestinal metaplasia

Objective Cyclooxygenase-2 (COX-2) expression is increased in gastric cancer. We examined COX-2 expression in early stage gastric cancer and background mucosa to elucidate the role of COX-2 in gastric carcinogenesis. Methods Thirty-three early gastric cancers obtained from 30 patients infected with Helicobacter pylori were studied. Twenty-three patients had an intestinal, four patients had a diffuse, and three patients had both an intestinal and a diffuse type cancer. Expression of COX-2 protein was detected by immunohistochemistry by counting the number of positive staining cells per 100 cells. Results Mean COX-2 expression was 84.1 (SD 11.4) in 26 intestinal type cancers and was significantly higher than that in seven diffuse type cancers (23.1 ± 9.7) (P < 0.001). In three patients who had both the intestinal and the diffuse type cancer, COX-2 expression was 92, 90 and 83 in the intestinal type cancer and only 25, 24 and 7 in the corresponding diffuse type cancer. In 18 patients who had intestinal metaplasia (15 had incomplete metaplasia), COX-2 expression was 60.2 (24.2) in the crypts with metaplasia while it was only 16.8 (10.7) in the crypts without metaplasia (P < 0.001). Conclusions COX-2 expression may be associated with the carcinogenesis of the intestinal type gastric cancer and, speculatively, inhibition of COX-2 might have preventative effects on the intestinal type gastric cancer.

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.