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Biomedical subjects

Toru Takeuchi

Publications and source records attributed to Toru Takeuchi.

23 records · Page 2Linked to original sources

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. METHODS: One hundred and thirty-five H. pylori-positive patients with early gastric carcinoma and 141 age- and sex-matched H. pylori-positive controls without gastric carcinoma were involved in the study. The widths of gastric body folds were measured by double-contrast radiographs. The mutagenicity of gastric juice was assayed using the Ames test and Salmonella typhimurium TA-98 or TA-100 with S9-mix. Levels of 8-hydroxydeoxyguanosine (8-OHdG) in gastric mucosa were examined using high-performance liquid chromatographic-electrochemical detection. RESULTS: An upward shift in the distribution of gastric fold widths in H. pylori-positive patients with early gastric carcinoma was found. Enlarged-fold gastritis (fold width >/=5 mm) was observed in 81% of the patients with gastric carcinoma, compared with 46% of H. pylori-positive controls. The odds ratio for gastric carcinoma increased with increasing fold width to a maximum of 35.5 in persons with fold width >/=7 mm. The prevalence of diffuse-type early gastric carcinoma in the body region increased with increasing fold width. The mutagenicity of gastric juice from the patients with enlarged-fold gastritis was significantly higher than that in H. pylori-negative controls and H. pylori-positive patients without enlarged folds. Mucosal 8-OHdG levels in the body region of patients with enlarged-fold gastritis were significantly higher than in H. pylori-negative controls and H. pylori-positive patients without enlarged-fold gastritis. Eradication of H. pylori significantly decreased the mutagenicity of gastric juice and 8-OHdG levels in the gastric mucosa from patients with enlarged-fold gastritis. CONCLUSION: A significant association is suggested between enlarged-fold gastritis and gastric carcinoma.

Adult↗

Expression of cytokine mRNAs in mice cutaneously exposed to formaldehyde.

In this study, we have investigated the expression of cytokine mRNAs in mice cutaneously exposed to formaldehyde using semiquantitative RT-PCR. We show that formaldehyde induced the long-lasting expression of IL-4 and IFN-gamma mRNAs and the transient expression of IL-13 mRNA in mouse spleen and draining lymph nodes. The transient increases in IL-2, IL-15, IL-12p40, IL-15 and IL-18 mRNAs, but long-lasting IL-15 mRNA were only seen in the formaldehyde-exposed mouse spleen. Moreover, a weak contact hypersensitivity (CH) and the significant increases in IL-4 and IFN-gamma mRNAs were detected in the ear skin of formaldehyde-cutaneously exposed mice when rechallenged mouse ears. Furthermore, CH as measured by mouse ear swelling response was positively correlated with IL-4 and IFN-gamma mRNA levels in the challenged ears. This study thus suggests that the induction of Th1 and Th2 cytokine mRNAs, particularly IL-4 and IFN-gamma, are a common immunological feature caused by contact allergens irrespective of strong or weak contact allergens. The analysis of IL-4 and IFN-gamma mRNAs may be useful markers in establishing the novel test for predicting chemical sensitizing potentials.

Administration, Cutaneous↗

Nitration and chlorination of folic acid by peroxynitrite and hypochlorous acid, and the selective binding of 10-nitro-folate to folate receptor beta.

The aim of this work was to characterize folates modified by ONOO(-) and HOCl and to evaluate the binding capacity of folates modified by ONOO(-) to folate receptor alpha and beta. For the modification of folate by ONOO(-), folic acid was reacted with the combination of PMA activated PMN and PAPA NONOate or chemically synthesized ONOO(-). For the modification of folate by HOCl, folic acid was reacted with the combination of MPO and H(2)O(2) or NaOCl. The structures of products were determined by 1H-NMR and MALDI-TOF mass. Nitrated folate species were identified as 10-nitro-folate and 12-nitro-folate, and chlorinated folate was identified as 12-chloro-folate. The 10-nitro-folate showed the selective binding to FR-beta, compared to folic acid.

Carrier Proteins↗

Serum bisphenol a concentrations showed gender differences, possibly linked to androgen levels.

To investigate human exposure to bisphenol A (BPA), a widely used endocrine disruptor, we measured serum BPA concentrations and analyzed the interrelation of BPA with sex-related hormones. BPA was detected in all human sera by a novel enzyme-linked immunosorbent assay. Serum BPA concentrations were significantly higher in normal men (1.49 +/- 0.11 ng/ml; P < 0.01) and in women with polycystic ovary syndrome (1.04 +/- 0.10 ng/ml; P < 0.05) compared with normal women (0.64 +/- 0.10 ng/ml). There were significant positive correlations between serum BPA and total testosterone (r = 0.595, P < 0.001) and free testosterone (r = 0.609, P < 0.001) concentrations in all subjects and likewise between serum BPA and total testosterone (r = 0.559, P < 0.01) and free testosterone (r = 0.598, P < 0.001) concentrations in all female subjects, but not between serum BPA and other sex-related hormone concentrations in any group. These findings showed that there are gender differences in serum BPA concentrations, possibly due to differences in the androgen-related metabolism of BPA.

Adult↗

Lack of direct involvement of 8-hydroxy-2'-deoxyguanosine in hypoxanthine-guanine phosphoribosyltransferase mutagenesis in V79 cells treated with N,N'-bis(2-hydroxyperoxy-2-methoxyethyl)-1,4,5,8-naphthalenetetracarboxylic-diimide (NP-III) or riboflavin.

The object of this study is to investigate the relationship between a typical product of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine (8OHdG), and mutagenesis in V79 cells through a molecular analysis of hypoxanthine-guanine phosphoribosyltransferase (hprt) gene mutants. We performed a direct sequencing analysis of the cDNA of mutants obtained after treatment with N,N'-bis(2-hydroxyperoxy-2-methoxyethyl)-1,4,5,8-naphthalenetetracarboxylic-diimide (NP-III) or riboflavin, each of which induces the formation of 8OHdG in cellular DNA upon UVA irradiation. The frequency of mutation after both treatments was no more than 2 to 5 times the control value. A considerable number of the mutants could not be amplified by RT-PCR, and this was also the case for the control mutants. Among the mutants analyzed, deletions and a TA-->AT transversion occurred predominantly. The reasons for the weak association of induction of 8OHdG with frequency of mutation and the possible mechanism of oxidative-stress-derived mutagenesis are discussed.

8-Hydroxy-2'-Deoxyguanosine↗