Tatsuya Takeshita

Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer

We conducted a longitudinal cohort study to determine the association of Helicobacter pylori infection and the progression of chronic atrophic gastritis (CAG) with gastric cancer. A cohort of 4,655 healthy asymptomatic subjects was followed for a mean period of 7.7 years. H. pylori infection was established by serum specific antibodies and the presence of CAG was confirmed by serum pepsinogen. During the follow‐up period, 45 gastric cancer cases were detected (incidence rate, 126/100,000 person‐years). A univariate analysis after adjustment for age showed that both H. pylori and CAG were significantly associated with gastric cancer. To clarify the interaction between H. pylori and CAG, an analysis stratified by H. pylori‐ and CAG–status was performed. No cancer developed in the H. pylori(−)/CAG(−) group during the study period. This supports the theory that it is quite rare for any type of gastric cancer to develop in an H. pylori‐free healthy stomach. With the progression of H. pylori‐induced gastritis, the risk of gastric cancer increased in a stepwise fashion from CAG‐free gastritis [H. pylori(+)/CAG(−) group] (HR=7.13, 95%CI=0.95‐53.33) to CAG [H. pylori(+)/CAG(+) group] (HR=14.85, 95%CI=1.96–107.7) and finally to severe CAG with extensive intestinal metaplasia [H. pylori(−)/CAG(+) group] (HR=61.85, 95%CI=5.6–682.64) in which loss of H. pylori from the stomach is observed. Therefore, it is probable that H. pylori alone is not directly associated with stomach carcinogenesis. Instead, H. pylori appears to influence stomach carcinogenesis through the development of CAG. The observed positive correlation between the extent of H. pylori‐induced gastritis and the development of cancer was strong, especially for the intestinal type. These results are compelling evidence that severe gastritis with extensive intestinal metaplasia is a major risk factor for gastric cancer, and they confirm the previously described model of stomach carcinogenesis: the gastritis‐metaplasia‐carcinoma sequence.

Intramolecular epitope spreading among anti-caspase-8 autoantibodies in patients with silicosis, systemic sclerosis and systemic lupus erythematosus, as well as in healthy individuals

Dysregulation of apoptosis through the Fas‐Fas ligand pathway is relevant in autoimmune disease onset. We recently reported elevated serum levels of sFas in patients with silicosis, systemic sclerosis (SSC) and systemic lupus erythematosus (SLE), and proposed a block of apoptosis in the pathogenesis. The disturbance of apoptosis in lymphocytes including autoreactive clones could induce autoantibody production. Since autoantibodies directed against unknown antigens are present in the sera of these patients, the sera samples were examined for the presence of autoantibodies directed to caspase‐8.

Lifestyles and mental health status are associated with natural killer cell and lymphokine-activated killer cell activities

We investigated the association of lifestyle and mental health status with natural killer (NK) cell and lymphokine-activated killer (LAK) cell activities in healthy males. NK cell activity was determined in 105 male workers and LAK cell activity was determined in 54 male workers. Peripheral blood was obtained from each subject and peripheral blood mononuclear cells (PBMC) were isolated from the blood. These PBMC were used as effector cells. LAK cells were generated by incubation of PBMC with interleukin-2 for 72 h. NK cell activity against NK-sensitive K562 cells and LAK cell activity against NK-resistant Raji cells were examined by 51Cr release assay. Overall lifestyles were evaluated according to the answers on a questionnaire regarding eight health practices (cigarette smoking, alcohol consumption, eating breakfast, hours of sleep, hours of work, physical exercise, nutritional balance, mental stress). Subjects with a good overall lifestyle showed significantly higher NK cell (P < 0.05) and LAK cell (P < 0.05) activities than those with a poor overall lifestyles. Among eight lifestyle factors, cigarette smoking has relatively strong effects on NK cell and LAK cell activities. Subjects who complained of unstable mental status had significantly lower NK cell activity than those who reported stable mental status. When subjects were divided into four groups by lifestyle and mental health status, subjects who had poor or moderate lifestyle and reported unstable mental status showed the lowest NK cell activity and subjects who had good lifestyle and reported stable mental status showed the highest NK cell activity among four groups.

Helicobacter pylori -induced enlarged-fold gastritis is associated with increased mutagenicity of gastric juice, increased oxidative DNA damage, and an increased risk of gastric carcinoma

Background and Aim:  The severe inflammation, increased cell proliferation and marked acid inhibition observed in subjects with Helicobacter pylori‐associated enlarged‐fold gastritis suggest that enlarged‐fold gastritis may be a risk factor for gastric carcinoma. The purpose of the present study was to determine whether a relationship exists between enlarged‐fold gastritis and gastric carcinoma.

Arsenic Induces DNA Damage via Reactive Oxygen Species in Human Cells

To elucidate arsenic-induced oxidative DNA damage, the genotoxicity of arsenic in human cells was comparatively studied with single cell gel electrophoresis (SCGE) assay in combination with the observation of the protective effects of dimethyl sulfoxide (DMSO) and catalase. Arsenic, at the concentration of 2.4 μM by coincubation for 24 hours, significantly induced DNA damage in HL60, a human promyelocytic leukemia cell line. In contrast, significant DNA damage was found in human mononucleocytes at the concentration of 4.8 μM or above. The cells were incubated separately with DMSO (12 mM/l), a well-known hydroxyl radical (OH−) scavenger, and catalase (1,300 U/ml), a hydrogen peroxide (H2O2) scavenger, for 6 hours and then further coincubated with various concentrations of arsenic for 24 hours at 37°C and 5% CO2. The findings showed that both DMSO and catalase significantly reduced the arsenic-induced tail moment, a parameter of total damaged DNA, in HL60 and mononucleocytes. Hence our findings indicate that arsenic, with micromolar concentrations, induces typical and various extents of DNA damage in human cells via reactive oxygen species in a dose-dependent manner.

Association of ALDH2 Genotypes and Alcohol Consumption with Periodontitis

There is little information regarding the association between alcohol consumption and periodontitis risk. We assessed whether alcohol consumption and ALDH2 genotypes were associated with periodontitis. Subjects’ lifestyle was examined by a self-administered questionnaire, and the percentage of pocket depths ≥ 3.5 mm was used as a periodontal parameter. ALDH2 genotypes were determined with the use of a PCR/RFLP method. Multiple logistic analyses showed that alcohol consumption was significantly associated with periodontitis, and its odds ratio was 1.98. There was no significant relationship between periodontal status and ALDH2 genotypes. However, ALDH2*1/*2 subjects who consumed ≥ 33 g/day of alcohol had a significantly greater percentage of pocket depths ≥ 3.5 mm than those whose daily consumption was lower, while there was no significant difference in periodontal status associated with alcohol consumption in ALDH2*1/*1 subjects. Our results suggest that alcohol consumption may be a risk indicator for periodontitis in ALDH2*1/*2 subjects who consume larger amounts of alcohol.

Correlation between saliva glycated and blood glycated proteins

ObjectivesBlood and saliva samples were obtained to examine if there is a correlation between saliva glycated protein and blood glycated protein.MethodsBlood and saliva samples of 51 male workers were collected. The fructosamine and hydrazine methods were used to measure saliva glycated protein. HbA1c, fructosamine and blood glucose were measured as indices of blood glycated protein, and the correlation between blood glycated protein and saliva glycated protein was examined.ResultsSaliva fructosamine glycated protein showed a significant correlation with HbA1c and blood glucose (r=0.449; p=0.001 and r=0.445; p=0.001, respectively). No correlation was identified between saliva hydrazine glycated protein and the index of blood glycated protein.ConclusionsBlood glycated protein and blood glucose could be estimated by measuring saliva glycated protein.

Effects of (-)-Epigallocatechin Gallate (EGCG) on DNA Strand Breaks as Evaluated by Single-cell Gel Electrophoresis (SCG) in Human Lymphocytes

Abstract(−)-Epigallocatechin gallate (EGCG), a catechin polyphenol component, is the main ingredient of green tea extract. Although the anti-carcinogenic and cancer inhibitory effects of EGCG have been widely reported, its genotoxicity is not clear and seldom reported. In this study, we examined the effects of EGCG on DNA strand breaks in the isolated lymphocytes and whole blood lymphocytes obtained from two smoking subjects and a nonsmoking healthy subject using a single cell gel electrophoresis (SCG) assay. The results showed that after 2 hrs of treating the isolated lymphocytes from the smokers, EGCG induced a significant, increase in DNA strand breaks at concentrations from 2.5×10−5 M to 2.0×10−4 M, while after 2 hrs of treating the whole blood obtained from the same smokers, EGCG suppressed the DNA strand breaks in the lymphocytes at concentrations of 1.0×10−4 M and 2.0×10−4 M. A similar suppressive result was also shown in the whole blood lymphocytes from the nonsmoker at nearly the same concentrations, while at concentrations of 1.0×10−3 M or 2.0×10−3 M, EGCG induced a significant increase in DNA strand breaks in the whole blood lymphocytes from the nonsmoker. This result suggests that EGCG is not only inhibitory against DNA strand breaks in whole blood, but also genotoxic to the isolated or whole blood lymphocytes at high concentrations. Thus, more research is needed to comprehensively assess the effects of EGCG on genetic materials.

Increasing obesity among male workers in Japan: 1992-1997.

ObjectiveTo examine changes in the Body Mass Index (BMI) and in the prevalence of obesity among male Japanese workers after five years.DesignFollow-up study, based on data from annual health checkups performed at workplaces.Subjects and MethodsWe had access to the data for a total of 63,951 male workers aged 20 through 54 years in 1992 who were examined in both 1992 and 1997. In quinquennial cohorts, we compared the findings for mean BMI and the prevalence of obesity in 1992 with the findings in 1997.ResultsBetween 1992 and 1997, in all cohorts the mean BMI increased significantly. For each adjacent cohort pair the mean BMI value in 1997 was significantly higher than in 1992. In 1992, 21.3% of all subjects were obese, increasing by 3.4% after five years to 24.7% in 1997. In the younger 1968–1972 and 1963–1967 cohorts the prevalence of obesity increased by 6.3% during five years. The significant increase in the obesity prevalence was observed from 1992 to 1997 for each age-adjusted cohort.ConclusionsThese results suggest a substantial increase in obesity among male Japanese workers. The notable increase in the prevalence of obesity among young male adults and the general trend toward widespread obesity during five years signal an increasing risk of lifestyle-related diseases.

Application of specific brain function evaluation by optical topography

ObjectivesTo use the evaluation of a specific brain function obtained by optical topography. This system uses a non invasive method to measure brain function unlike other major systems.MethodsTwelve optical fibers were attached to the subject’s head. Hemodynamic changes in the motor cortex were measured during finger tapping before and after alcohol intake for eachALDH2 genotype.ResultsDifferent hemodynamic changes in the motor cortex were observed among, theALDH2 genotypes.ConclusionsOptical topography is a useful tool for evaluating specific brain functions. Further research is needed on the relations between various environmental factors and brain functions by optical topography.