Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: We previously found that a forest bathing (shinrin-yoku) program significantly reduced the scores for depression, anxiety, anger, fatigue, and confusion and increased the score for vigor in the profile of mood states (POMS) test and showed a potential preventive effect on the depressive status in both males and females. In the present study, we investigated the effects of a forest bathing program on the level of serotonin in serum, depressive symptoms and subjective sleep quality in middle-aged males. METHODS: Twenty healthy male subjects aged 57.3 ± 8.4 years were selected after obtaining informed consent. These subjects took day trips to a forest park, the birthplace of forest bathing in Japan named Akasawa Shizen Kyuyourin, Agematsu, Nagano Prefecture (situated in central Japan), and to an urban area of Nagano Prefecture as a control in June 2019. On both trips, they walked 2.5 km for 2 hours each in the morning and afternoon on Saturday and Sunday, respectively. Blood was sampled in the afternoon before and after each trip. Concentrations of serotonin and lactic acid in serum were measured. The POMS test and a questionnaire for subjective sleep quality were conducted before and after the trips. Ambient temperature and humidity were monitoring during the trips. The Ethics Committees of the Nippon Medical School and Nagano Prefectural Kiso Hospital approved this study. RESULTS: The forest bathing program significantly increased level of serotonin in serum, and significantly increased the score for vigor and decreased the score for fatigue in the POMS test. The forest bathing program also improved the sleepiness on rising and feeling refreshed (recovery from fatigue) in the Oguri-Shirakawa-Azumi sleep inventory MA version (OSA-MA). CONCLUSIONS: Taken together, the present study suggests that forest bathing may have potential preventive effects on depression (depressive status).

DOI： 10.1265/ehpm.22-00136

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)  

File： 日本衛生学会賞受賞講演抄録.pdf

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：English  

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Language：Japanese   Publisher：(一社)日本衛生学会  

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Language：Japanese   Publisher：日本医科大学医学会  

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Authorship：Lead author,　Corresponding author   Language：French  

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：HINDAWI PUBLISHING CORP  

In the present study, we investigated the effects of a forest bathing on cardiovascular and metabolic parameters. Nineteen middle-aged male subjects were selected after they provided informed consent. These subjects took day trips to a forest park in Agematsu, Nagano Prefecture, and to an urban area of Nagano Prefecture as control in August 2015. On both trips, they walked 2.6 km for 80 min each in the morning and afternoon on Saturdays. Blood and urine were sampled before and after each trip. Cardiovascular and metabolic parameters were measured. Blood pressure and pulse rate were measured during the trips. The Japanese version of the profile of mood states (POMS) test was conducted before, during, and after the trips. Ambient temperature and humidity were monitored during the trips. The forest bathing program significantly reduced pulse rate and significantly increased the score for vigor and decreased the scores for depression, fatigue, anxiety, and confusion. Urinary adrenaline after forest bathing showed a tendency toward decrease. Urinary dopamine after forest bathing was significantly lower than that after urban area walking, suggesting the relaxing effect of the forest bathing. Serum adiponectin after the forest bathing was significantly greater than that after urban area walking.

DOI： 10.1155/2016/2587381

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SAGE PUBLICATIONS INC  

We previously found that ziram, a carbamate pesticide, significantly reduced perforin, granzyme A (GrA), granzyme B (GrB), granzyme 3/K (Gr3/K), and granulysin (GRN) levels in NK-92MI cells, a human natural killer (NK) cell line. To investigate whether other carbamate pesticides also show similar toxicity on human NK cells, we conducted further experiments with NK-92CI cells, a human NK cell line, using a more sensitive assay. We previously confirmed that NK-92CI cells express CD56, perforin, GrA, GrB, Gr3/K, and GRN and are highly cytotoxic to K562 cells in a chromium release assay, which are more sensitive to organophosphorus pesticides and ziram than the NK-92MI cell line. NK-92CI cells were treated with ziram, thiram, maneb, or carbaryl at various concentrations for 4-24 h at 37 degrees C in vitro. Thereafter, intracellular levels of perforin, GrA, GrB, Gr3/K, and GRN were determined by flow cytometry. It was found that all carbamate pesticides significantly reduced the intracellular levels of perforin, GrA, GrB, Gr3/K, and GRN in NK-92CI cells in a dose-dependent manner. However, the strength of the effect differed among the pesticides, and the order was thiram > ziram > maneb > carbaryl. In addition, it was also found that the degree of the reductions differed among the five proteins, with perforin more sensitive to pesticides than GRN, GrA, GrB, and Gr3/K, and the order was perforin > GRN > Gr3/K ? GrA ? GrB.

DOI： 10.1177/0394632015582334

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

We previously found that carbamate pesticides induced significant apoptosis in human natural killer cells. To investigate whether carbamate pesticides also induce apoptosis in human T lymphocytes, in the present study Jurkat human T cells were treated in vitro with thiram, maneb, carbaryl or ziram. Apoptosis was determined by FITC-Annexin-V/PI staining. To explore the mechanism of apoptosis, intracellular levels of active caspase 3 and mitochondrial cytochrome-c release were determined by flow cytometry. We found that thiram, ziram, maneb and carbaryl also induced apoptosis in a time- and dose-dependent manner in the human T cells. However, the strength of the apoptosis-inducing effect differed among the pesticides, with the: thiram > ziram > maneb > carbaryl. Moreover, thiram significantly increased the intracellular level of active caspase 3 and caspase inhibitors significantly inhibited apoptosis. Thiram also significantly caused mitochondrial cytochrome-c release. These findings indicate that carbamate pesticides can induce apoptosis in human T cells, and the apoptosis is mediated by the activation of caspases and the release of mitochondrial cytochrome-c.

DOI： 10.3390/ijerph120403633

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The present study investigated the well-being effects of short-term forest walking and viewing ("forest bathing"). The hypothesis in our study was that both environment (forest vs. urban) and activity (walking and viewing) would influence psychological outcomes. An additional aim was to enhance basic research using several psychological methods. We conducted the experiments using 45 respondents in four areas of Japan from August to September, 2011. The hypothesis in our study was supported, because significant interaction terms between the environment and activity were confirmed regarding the Profile of Mood States (POMS) indexes, Restorative Outcome Scale (ROS) and Subjective Vitality Scale (SVS). No statistical differences between the two experimental groups in any of the ten scales were found before the experiment. However, feelings of vigor and positive effects, as well as feelings of subjective recovery and vitality were stronger in the forest environment than in the urban environment.

DOI： 10.3390/ijerph110707207

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOLIFE SAS  

We previously found that ziram, a carbamate fungicide, significantly induced apoptosis and necrosis in human NK-92MI, a natural killer cell line. To investigate whether other carbamate pesticides also induce apoptosis and necrosis in human natural killer cell, we conducted further experiments with NK-92CI, a human natural killer cell line using a more sensitive assay. NK-92CI cells were treated with ziram, thiram, maneb or carbaryl at 0.031-40 mu M for 2-24 h in the present study. Apoptosis and necrosis were determined by FITC-Annexin-V/PI staining. To explore the mechanism of apoptosis, intracellular levels of active caspases 3 and mitochondrial cytochrome-c release were determined by flow cytometry. We found that ziram and thiram also induced apoptosis and necrosis in a time- and dose-dependent manner; however, maneb and carbaryl induced apoptosis and necrosis only at higher doses in NK-92CI cells. The strength of the apoptosis-inducing effect differed among the pesticides, and the order was as follows: thiram > ziram > maneb > carbaryl. NK-92CI was more sensitive to ziram than NK-92MI. Moreover, ziram and thiram significantly increased the intracellular level of active caspase 3 in NK92CI and caspase inhibitor significantly inhibited the apoptosis. Ziram and thiram significantly caused mitochondrial cytochrome-c release in NK-92CI. These findings indicate that carbamate pesticides can induce apoptosis in natural killer cells, and the apoptosis is mediated by both the caspase-cascade and mitochondrial cytochrome-c pathways.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：HINDAWI PUBLISHING CORP  

Background. Despite increasing attention toward forest therapy as an alternative medicine, very little evidence continues to be available on its therapeutic effects. Therefore, this study was focused on elucidating the health benefits of forest walking on cardiovascular reactivity. Methods. Within-group comparisons were used to examine the cardiovascular responses to walking in forest and urban environments. Forty-eight young adult males participated in the two-day field research. Changes in heart rate variability, heart rate, and blood pressure were measured to understand cardiovascular reactivity. Four different questionnaires were used to investigate the changes in psychological states after walking activities. Results. Forest walking significantly increased the values of ln(HF) and significantly decreased the values of ln(LF/HF) compared with the urban walking. Heart rate during forest walking was significantly lower than that in the control. Questionnaire results showed that negative mood states and anxiety levels decreased significantly by forest walking compared with urban walking. Conclusion. Walking in the forest environment may promote cardiovascular relaxation by facilitating the parasympathetic nervous system and by suppressing the sympathetic nervous system. In addition, forest therapy may be effective for reducing negative psychological symptoms.

DOI： 10.1155/2014/834360

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Authorship：Corresponding author   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)  

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CAMBRIDGE UNIV PRESS  

Dietary probiotics supplementation exerts beneficial health effects. Since cigarette smoking reduces natural killer (NK) activity, we evaluated the effect of Lactobacillus casei Shirota (LcS) intake on NK cytotoxic activity in male smokers. The double-blind, placebo-controlled, randomised study was conducted on seventy-two healthy Italian blue-collar male smokers randomly divided for daily intake of LcS powder or placebo. Before and after 3 weeks of intake, peripheral blood mononuclear cells were isolated and NK activity and CD16(+) cells' number were assessed. Daily LcS intake for 3 weeks significantly increased NK activity (P<0.001). The increase in NK activity was paralleled by an increase in CD16(+) cells (P<0.001). Before intake, NK cytotoxic activity inversely correlated with the number of cigarettes smoked (R-0.064). LcS intake prevented the smoke-dependent expected NK activity reduction. The analysis of the distribution of changes in smoke-adjusted NK activity demonstrated that the positive variations were significantly associated with LcS intake, while the negative variations were associated with placebo intake (median value of distributions of differences, 20.98 lytic unit (LU)/10(7) cells for LcS v. -4.38 LU/10(7) cells for placebo, P=0.039). In conclusion, 3 weeks of daily LcS intake in Italian male smokers was associated with a higher increase in cytotoxic activity and CD16(+) cells' number in comparison to the placebo intake group.

DOI： 10.1017/S0007114511005630

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Language：English   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.jjcc.2012.04.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER HEIDELBERG  

Ziram as a dithiocarbamate fungicide is widely used throughout the world in agriculture. We previously found that ziram significantly inhibited cytotoxic T lymphocyte activity in a dose-dependent manner. To explore the mechanism of this inhibition, we investigated ziram-induced apoptosis in human T lymphocytes. Jurkat T cells were treated with ziram at 0.031-1 mu M for 2-24 h. Freshly isolated primary human T cells were treated with ziram at 0.0625-1 mu M for 15 and 24 h. Apoptosis was determined by FITC-Annexin V/PI staining and the TUNEL assay. To explore the mechanism of apoptosis, intracellular levels of active caspases 3, 3/7, 8, and 9 and pan-caspase and mitochondrial cytochrome-c release were determined by flow cytometry. Disruption to mitochondrial transmembrane potential was determined with a MitoLight((TM)) Apoptosis Detection Kit. We found that ziram induced apoptosis in a time- and dose-dependent manner in both Jurkat cells and primary human T cells. The primary human T cells were more sensitive to ziram than the Jurkat cell line. Ziram induced increases in active caspases 3, 3/7, 8, and 9 and pan-caspase in a dose-dependent manner, and a caspase-3 inhibitor, Z-DEVD-FMK, partially but significantly inhibited the apoptosis. Moreover, a general caspase inhibitor, Z-VAD-FMK, significantly and almost completely blocked the apoptosis. Ziram also disrupted mitochondrial transmembrane potential and caused mitochondrial cytochrome-c release. These findings indicate that ziram can induce apoptosis in human T cells, and the apoptosis is mediated by both the caspase-cascade and the mitochondria/cytochrome-c pathways.

DOI： 10.1007/s00204-011-0791-1

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Ziram is a carbamate pesticide, which is widely used throughout the world as a fungicide in agriculture and as an accelerating agent in latex production. In the present study, we investigated the effect of ziram at 0.031-4 mu M in vitro on human natural killer (NK) and lymphokine-activated killer (LAK) and murine cytotoxic T lymphocyte (CTL) activity and found that it significantly inhibited all three activities in a concentration-dependent manner. To explore the mechanism of ziram-induced inhibition of NK activity, NK-92MI cells, a human NK cell line, were used. We previously confirmed that NK-92MI cells express CD56, perforin, granzyme (Gr) A, GrB, Gr3/K, and granulysin and are highly cytotoxic to K562 cells in the chromium release assay. NK-92MI cells were treated with ziram at 0.125-4 mu M for 4 or 16 h at 37A degrees C in vitro. Then, intracellular levels of perforin, GrA, GrB, Gr3/K, and granulysin were determined by flow cytometry. It was found that ziram significantly reduced Gr3/K, granulysin, perforin, GrA, and GrB levels. The extent of the decrease differed among the proteins, and the order was as follows: Gr3/K > granulysin > perforin, GrA, and GrB. Taken together, these findings suggest the ziram-induced inhibition of NK, LAK, and CTL activities to be at least partially mediated by decreases in the intracellular levels of Gr3/K, granulysin, perforin, GrA, and GrB.

DOI： 10.1007/s00204-011-0771-5

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Language：Japanese   Publishing type：Research paper (scientific journal)  

CiNii Books

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Biolife s.a.s.  

We previously found that ziram, a dithiocarbamate fungicide, significantly inhibited natural killer (NK) activity in a dose-dependent manner. To explore the mechanism of this inhibition, we investigated ziram-induced apoptosis in human NK cells. Human NK-92MI cells were treated with ziram at 0.0625-4 μM for 2-64 h. Apoptosis was determined by FITC-Annexin-V/PI staining. To explore the mechanism of apoptosis, intracellular levels of active caspases 3, 3/7, 8, and 9 and pan-caspase and mitochondrial cytochrome-c release were determined by flow cytometry. Disruption to mitochondrial transmembrane potential was determined with a MitoLight™ Apoptosis Detection Kit. It was found that ziram induced apoptosis in a dose- and time-dependent manner in human NK cells. Ziram increased the intracellular levels of active caspases 3, 3/7, 8, and 9 and pan-caspase in a dose-dependent manner, and a caspase-3 inhibitor, Z-DEVD-FMK, and a general caspase inhibitor, Z-VAD-FMK, partially but significantly inhibited the apoptosis. Ziram also disrupted mitochondrial transmembrane potential and caused mitochondrial cytochrome-c release in a dose-dependent manner. These findings indicate that ziram can induce apoptosis in human NK cells, and the apoptosis is at least mediated by both the caspase-cascade and the mitochondria/cytochroiolifeme-c pathways. Copyright © by BIOLIFE, s.a.s.

DOI： 10.1177/039463201202500406

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

We previously found that forest environments reduced stress hormones such as adrenaline and noradrenaline and showed the relaxing effect both in male and female subjects. In the present study, we investigated the effects of walking under forest environments on cardiovascular and metabolic parameters. Sixteen healthy male subjects (mean age 57.4 +/- 11.6 years) were selected after obtaining informed consent. The subjects took day trips to a forest park in the suburbs of Tokyo and to an urban area of Tokyo as a control in September 2010. On both trips, they walked for 2 h in the morning and afternoon on a Sunday. Blood and urine were sampled on the morning before each trip and after each trip. Blood pressure was measured on the morning (0800) before each trip, at noon (1300), in the afternoon (1600) during each trip, and on the morning (0800) after each trip. The day trip to the forest park significantly reduced blood pressure and urinary noradrenaline and dopamine levels and significantly increased serum adiponectin and dehydroepiandrosterone sulfate (DHEA-S) levels. Walking exercise also reduced the levels of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and urinary dopamine. Taken together, habitual walking in forest environments may lower blood pressure by reducing sympathetic nerve activity and have beneficial effects on blood adiponectin and DHEA-S levels, and habitual walking exercise may have beneficial effects on blood NT-proBNP levels.

DOI： 10.1007/s00421-011-1918-z

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Background: The aim of this study was to examine the association between serum insulin levels and components of the metabolic syndrome (MetS) in working women. Methods: The target subjects were 141 working women. Serum triglyceride, HDL cholesterol, uric acid, plasma insulin and plasma glucose were measured in addition to waist circumference and blood pressure. Results: MetS was diagnosed based on the modified criteria of the International Diabetes Federation, and was present in 7.1% (10/141) of the study subjects. Stepwise multiple regression analysis showed that some components of MetS were significantly associated with log-transformed values of the serum insulin. The standardized regression coefficient for the waist circumference, high density lipoprotein cholesterol, systolic blood pressure and age were 0.238, -0.333, 0.309 and -0.156, respectively. Conclusions: A statistically significant relationship existed between the components of MetS and the serum insulin levels in working women. © 2010 Diabetes India.

DOI： 10.1016/j.dsx.2010.12.005

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SAGE PUBLICATIONS LTD  

Fenitrothion (FNT) is used throughout the world as an insecticide in agriculture. To investigate the effect of FNT on the splenocytes and the underlying mechanism, FNT and its main metabolite, 3-methyl-4-nitrophenol (MNP), were administered orally to Wistar rats in daily doses of 0, 5 and 10 mg/kg, 4-5 days/week for 9 weeks. Splenocytes were harvested from control and exposed rats, and the following cell phenotypes were quantified by flow cytometry: (1) B cells (PE-CD45RA), (2) T cells (FITC-CD3), (3) T cell subsets (PE-CD4 and PerCP-CD8), (4) natural killer (NK) cells (FITC-CD161a), (5) macrophages (FITC-CD11b), and (6) granulocyte (PE-granulocyte). Body weight, weight of the spleen, and histopathological alterations of spleens were also examined. The percentage of splenic CD8+ T cells and the ratio of CD8/CD4 in the group receiving 10 mg/kg FNT, and the percentages of splenic CD3+ and CD8+ T cells in the group receiving 10 mg/kg MNP were significantly decreased compared with those in the controls. FNT exposure also significantly decreased the weight of the spleen and body weight. In addition, apoptotic lymphocytes in spleen were observed in FNT-exposed rats under transmission electron microscope. However, FNT and MNP exposures did not affect splenic NK cells, B cells, macrophages, and granulocytes. The above findings indicate that FNT and MNP may selectively affect splenic T cells in rats.

DOI： 10.1177/0960327110377525

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INFORMA HEALTHCARE  

Introduction. The relationship among lifestyle, aging and psychological wellbeing was evaluated in Japanese working men.
Methods. Self-administered questionnaire on six lifestyle factors and the General Health Questionnaire 12-item version (GHQ12) were administered to 3306 male workers. Health practice index (HPI) was calculated as a desirable lifestyle score by summing up each binary lifestyle score (0, 1), ranging from 0 to 6. To check validity of the study outcome, the authors repeated twice with 1 year interval. HPI was categorised into three groups by the score of 0-2, 3-4 and 5-6.
Results. The number of subjects categorised by HPI was 532, 1967 and 807, respectively. The mean value of GHQ12 significantly decreased as the HPI increased by adjusting age. Multiple regression analysis was conducted to predict GHQ12 by six lifestyle scores, and age, sleep, night snacking and exercise were significantly related to GHQ12. Multiple logistic regression analysis was conducted and age in 50s, two-shift work, sleep, night snacking and exercise were significantly associated with GHQ12.
Conclusion. Although cause-effect relationship cannot make clear, some of desirable health practices and aging were closely related to psychological wellbeing judged by GHQ12.

DOI： 10.3109/13685538.2010.493588

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Ziram as a dithiocarbamate fungicide is widely used throughout the world in agriculture and as an accelerating agent is used in latex production. In order to investigate ziram-induced apoptosis/necrosis and its underlying mechanism in human immune cells, a human monocyte-like cell line (U937) was treated with ziram at 0.0312-2 mu M for 2-24 h at 37A degrees C in a 5% CO(2) incubator. Apoptosis/necrosis induced by ziram was determined by analysis of FITC-Annexin-V/PI staining and the intracellular level of active caspase-3 by flow cytometry and DNA fragmentation analysis. We found that ziram induced apoptosis/necrosis in U937 in a time- and dose-dependent manner, as shown by FITC-Annexin-V/PI staining. DNA fragmentation was detected when cells were treated with 0.5, 1, or 2 mu M ziram for 24 h. Ziram also induced an increase in intracellular active caspase-3 in U937 cells in a dose-dependent manner, and a caspase-3 inhibitor, Z-DEVD-FMK, significantly inhibited the ziram-induced apoptosis. Moreover, it was found that ziram induced mitochondrial cytochrome c release in U937 cells. These findings indicate that ziram can induce apoptosis/necrosis in U937 cells, and this effect is partially mediated by activation of intracellular caspase-3 and mitochondrial cytochrome c release.

DOI： 10.1007/s00204-010-0586-9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：W B SAUNDERS CO LTD  

Objective: To provide scientific evidence supporting the efficacy of forest bathing as a natural therapy by investigating its physiological benefits using biological indicators in outdoor settings.
Study design: Within-group comparisons were used to examine psychological and physiological responses to exposure to real forest and urban environments.
Methods: Young Japanese male adults participated in a 3-day, 2-night field experiment. Physiological responses as well as self-reported psychological responses to forest and urban environmental stimuli were measured in real settings. The results of each indicator were compared against each environmental stimulus.
Results: Heart rate variability analysis indicated that the forest environment significantly increased parasympathetic nervous activity and significantly suppressed sympathetic activity of participants compared with the urban environment. Salivary cortisol level and pulse rate decreased markedly in the forest setting compared with the urban setting. In psychological tests, forest bathing significantly increased scores of positive feelings and significantly decreased scores of negative feelings after stimuli compared with the urban stimuli.
Conclusion: Physiological data from this field experiment provide important scientific evidence on the health benefits of forest bathing. The results support the concept that forest bathing has positive effects on physical and mental health, indicating that it can be effective for health promotion. Despite the small sample size in this study, a very clear tendency towards positive physiological and psychological outcomes in forests was observed. (C) 2010 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.puhe.2010.09.005

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOLIFE SAS  

Humans have enjoyed forest environments for ages because of the quiet atmosphere, beautiful scenery, mild climate, and fresh, clean air. In the present study, we found that visiting forest parks, but not a city, enhanced human natural killer (NK) activity, increased anti-cancer proteins, such as perforin, granzymes A and B, and granulysin in NK cells, and reduced the level of stress hormones in both male and female subjects. Moreover, this effect lasted for more than 30 days after the trips, suggesting that visiting a forest park once a month would enable individuals to maintain a higher level of NK activity. Phytoncides released from trees and the decreased production of stress hormones may partially contribute to the increased NK activity. Because NK cells can kill tumor cells by releasing anti-cancer proteins, and visiting forest parks increases NK activity and the amount of anti-cancer proteins; therefore, the above findings suggest that visiting forest parks may have a preventive effect on cancer generation and progression.

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Aims: There is an ethnic difference of obesity index to diagnose metabolic syndrome. The authors explored the optimal cut-off levels for body mass index (BMI) and waist circumference (WC) in relation to each component of metabolic syndrome. Materials and methods: Receiver operating characteristics (ROC) analysis was used to determine the optimal cut-off levels for each component of metabolic syndrome. This study included 4572 workers aged 42.5 ± 9.9 years. Results: The optimal BMI cut-off values for diabetes mellitus, hypertension or dyslipidemia varied from 23.0 to 24.3 kg/m2. As for WC, the optimal cut-off values varied from 83.0 to 83.7 cm. The optimal BMI cut-off values relating with one to three components of metabolic syndrome varied from 23.2 to 25.3 kg/m2. As for WC, the optimal cut-off values varied from 83.0 to 85.0 cm. Pair-wise comparison of ROC curves showed that WC has an advantage in relation to metabolic syndrome and its components compared with BMI. By logistic regression analysis, odds ratios of obesity indices for hypertension, dyslipidemia or the number of metabolic component were all significantly increased. As for diabetes mellitus, odds ratios of BMI ≥25 and WC ≥85 significantly increased, respectively. Conclusions: Japanese criteria of obesity in metabolic syndrome in man may be appropriate for diabetes mellitus. Ethnic difference in criteria of obesity in Asian metabolic syndrome exists, and mutual comparisons in the prevalence of metabolic syndrome have a difficulty to conduct. © 2010 Diabetes India. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.dsx.2010.05.012

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Ethyl tertiary-butyl ether (ETBE) is a motor fuel oxygenate used in reformulated gasoline. The current use of ETBE in gasoline or petrol is modest but increasing. To investigate the effects of ETBE on splenocytes, mice were exposed to 0 (control), 500 ppm, 1750 ppm, or 5000 ppm of ETBE by inhalation for 6 h/day for 5 days/wk over a 6- or 13-week period. Splenocytes were harvested from the control and exposed mice, and the following cell phenotypes were quantified by flow cytometry: (1) B cells (PerCP-Cy5.5-CD45R/B220), (2) T cells (PerCP-Cy5-CD3e), (3) T cell subsets (FITC-CD4 and PE-CD8a), (4) natural killer (NK) cells (PE-NK1.1), and (5) macrophages (FITC-CD11b). Body weight and the weight of the spleen were also examined. ETBE-exposure did not affect the weight of the spleen or body weight, while it transiently increased the number of RBC and the Hb concentration. The numbers of splenic CD3+, CD4+, and CD8+ T cells, the percentage of CD4+ T cells and the CD4+/CD8+ T cell ratio in the ETBE-exposed groups were significantly decreased in a dose-dependent manner. However, ETBE exposure did not affect the numbers of splenic NK cells, B cells, or macrophages or the total number of splenocytes. The above findings indicate that ETBE selectively affects the number of splenic T cells in mice. Copyright © by BIOLIFE, s.a.s.

DOI： 10.1177/039463201102400403

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Objective: It has been suggested that the presence of a depressive state is a predictor of increase of the body weight. However, to precisely understand the nature of this relationship, the data should be controlled for other factors that can also be associated with weight gain.
Methods and Participants: To test the hypothesis that the presence of a depressive state is associated with future weight gain, a 4-year prospective occupation-based cohort study was conducted in male adult workers (N = 1730) at a railway company. Following the initial screening, follow-up information was obtained via a legally required annual health examination. The presence of a depressive state was identified using the Zung Self-Rating Depression Scale (SDS). The weight of each participant was measured to the nearest kilogram. Multiple logistic regression analysis was used to test the association between the depressive state and a weight gain of 4 kg or more over the 4-year study period after controlling for potentially confounding variables such as the age, smoking status, alcohol intake status, and physical activity.
Results: A weight gain of 4 kg or more over the 4-year study period was significantly associated with the depressive state, even after controlling for confounding variables (p < 0.05). Short-term longitudinal analysis also revealed an association between the depressive state and subsequent increase of the body weight.
Conclusion: Since the depressive state was demonstrated to be an important risk factor for increase of the body weight, further research on depression should be conducted with a view to providing effective health education.

DOI： 10.3233/WOR-2011-1114

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society for Hygiene  

Traditional thinking considered the nervous system, endocrine system and immune system to be independent of each other. However, it is now widely accepted that these systems interact through the psycho-neuro-endocrino-immune network. The nervous system affects the endocrine and immune systems by releasing neurotransmitters through the hypothalamus in the hypothalamic-pituitary portal circulation. The endocrine system affects the nervous and immune systems by secreting hormones and the immune system feeds back to the nervous and endocrine systems via cytokines. Forest therapy reduces sympathetic nervous activity, increases parasympathetic nervous activity, and regulates the balance of autonomic nerves. As a result, forest therapy decreases blood pressure and heart rate and has a relaxing effect. Forest therapy affects psychological responses via the brain and nervous system thereby decreasing the scores for anxiety, depression, anger, fatigue, and confusion, and increasing the score for vigor in the POMS test. Forest therapy acts on the endocrine system to reduce stress hormone levels such as urinary adrenaline, urinary noradrenaline, salivary cortisol, and blood cortisol levels and shows a relaxing effect. Forest therapy also acts directly and indirectly on the immune system to promote NK activity by increasing the number of NK cells and intracellular levels of anticancer proteins such as perforin, granulysin and granzymes. Taken together, forest therapy brings various effects on human health via the psycho-neuro-endocrino-immune network.<br>

DOI： 10.1265/jjh.66.645

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Other Link： https://jlc.jst.go.jp/DN/JALC/00379176238?from=CiNii

Language：Japanese   Publishing type：Research paper (scientific journal)  

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2011217100

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society for Hygiene  

DOI： 10.1265/jjh.66.643

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Aims: The prevalence of glucose intolerance in the Japanese adult population is increasing. In this study, the associated factors including lifestyles with glucose intolerance and its metabolism were explored. Methods: A cross-sectional study was conducted in 2008. The sample included 3203 working men aged 35-59 years. Age, six lifestyle-related factors, and metabolic components were used as variables to calculate the odds ratio for glucose intolerance, which were defined if his fasting plasma glucose was ≥110 mg/dL and &lt;126 mg/dL. Results: The prevalence of glucose intolerance was 8.4%, and it increased with 5-year interval of age (2.2, 5.0, 10.4, 15.2, and 17.5%, respectively). Odds ratios (95% confidence interval) of age, obesity, hypertension, dyslipidemia, and no current smoking for glucose intolerance were 1.11 (1.09-1.13), 1.66 (1.31-2.11), 1.90 (1.47-2.47), 1.86 (1.46-2.36), and 0.79 (0.62-0.998), respectively. In contrast, the odds ratios of drinking, sleeping, exercise, and dietary habit did not reach the significance level, although multiple regression analysis presented that subjects with regular exercise showed significantly lower serum insulin level. Conclusions: The risk of glucose intolerance was significantly correlated with obesity, high blood pressure, dyslipidemia and smoking habit. However, other lifestyle factors were not significantly associated with glucose intolerance. © 2010 Diabetes India. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.dsx.2010.05.015

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Introduction: Shift work has been reported to be associated with an increase in the metabolic syndrome (MetS). To clarify the association between the type of shift work and the risk of MetS, a cross-sectional field survey was conducted after adjusting for age and lifestyle factors. Methods: The subjects were 3007 Japanese males, aged 3464 years old, who were employees (1700 day and 1307 shift workers) of a car-manufacturing company. The standard Japanese criteria for the diagnosis of MetS was used. Age, smoking habit, drinking habit, sleeping habit and exercise habit were used as the independent variables. Results: The prevalence of MetS in the day workers, two-shift workers, and three-shift workers were 13.8 (234/1700), 10.7 (120/1125) and 17.6 (32/182), respectively. There was a significant difference in the prevalence between the two-shift workers and the day workers. Estimation of the odds ratios (95 confidence intervals) of age, two-shift work and habitual exercise for MetS were 1.03 (1.011.04), 0.77 (0.610.98) and 0.64 (0.510.81), respectively. Conclusion.Two-shift work was associated with lower risk of MetS, which is not in accordance with past reports. This finding should therefore be re-analysed, including investigation of the job content in each group. © 2010 Informa UK Ltd.

DOI： 10.3109/13685530903536692

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Introduction: Statistical information regarding the prevalence of metabolic syndrome among a wide age range of workers is insufficient. Methods: A total of 4278 men between the ages of 20 and 59 years participated in the study. Metabolic syndrome was diagnosed according to the International Diabetes Federation (IDF) and the National Cholesterol Education Program (NCEP) III criteria. Results: Overall, the prevalences of metabolic syndrome according to the IDF and NCEPIII criteria were 13.6 and 14.8, respectively. The prevalence of metabolic syndrome according to the IDF (NCEPIII) criteria among workers in their 20s, 30s, 40s, and 50s were 4.8 (6.1), 9.9 (12.2), 18.4 (21.6) and 25.8 (34.0), respectively. A plot of the prevalence of metabolic syndrome according to the NCEPIII criteria versus age had a steep gradient and increased sharply for men in their 50s. In contrast, a plot of the prevalence of metabolic syndrome according to the IDF criteria versus age increased in a linear manner. Conclusion.The prevalence of metabolic syndrome increased among workers according to age, but the increasing trend and the absolute prevalence of metabolic syndrome differed according to the two sets of diagnostic criteria used in this study. © 2010 Informa UK Ltd.

DOI： 10.3109/13685531003586983

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Background: Serum uric acid and hematological parameters play a significant role for cardiovascular disease (CVD). The metabolic syndrome (MetS) is associated with CVD, but the relationship between such blood parameters and MetS has not yet been precisely investigated in healthy workers. Methods: A total of 1088 male workers in a pharmaceutical company, aged 30-59 years with mean age of 43.2, were recruited. They participated in annual health examination in 2009. MetS was diagnosed according to the NCEP-ATP III criteria with modification on waist circumference. The relationships between blood parameters and MetS were analyzed according to four groups stratified by the number of components on MetS (0, 1, 2 and 3-5) in combination with age. Results: There was a significant trend of increase of variables such as hematocrit, white blood cell count (WBC), platelet count and serum uric acid as the number of components on MetS increased (p &lt; 0.05). Among them, there was a significant difference in the mean value except platelet count between a group of MetS and other groups. Furthermore, serum uric acid, WBC count and age were significantly associated with MetS by logistic regression analysis. Odds ratios and 95% confidence intervals in parentheses of uric acid and WBC against MetS were 1.47 (1.28-1.69) and 1.34 (1.21-1.49), respectively. Conclusions: Serum uric acid and WBC were associated with MetS, and such blood parameters increased as the number of MetS components increased in Japanese male workers. © 2010 Diabetes India. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.dsx.2010.05.016

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Objective: We performed a 1-year follow-up study to determine the effects of smoking status and insulin resistance on the prevalence of metabolic syndrome. Methods: This study included 2136 workers without metabolic syndrome at baseline who were followed for 1 year. The subjects were divided into four categories of smoking and work history, respectively. Insulin resistance was evaluated using the homeostasis model assessment for insulin resistance (HOMA-R). Results: The prevalence of metabolic syndrome after 1 year was 6.3%. A multiple logistic regression analysis showed that the current smokers category versus the nonsmokers category, a 0.1-point increase in the HOMA-R score, a 1-point increase in the uric acid level, age, and body mass index were significantly correlated with increased odds for metabolic syndrome, yielding odds ratios (95% confidence intervals) of 1.61 (1.09-2.39), 1.14 (1.04-1.25), 1.31 (1.12-1.54), and 1.06 (1.03-1.09), and 1.23 (1.15-1.31), respectively. Conclusions: Current smoking, insulin resistance, uric acid level, and age contributed positively to the prevalence of metabolic syndrome. In contrast, smoking cessation within 1 year and work history did not contribute to metabolic syndrome. © 2009 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.orcp.2009.12.004

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOLIFE SAS  

We previously reported that 2-night/3-day trips to forest parks enhanced human NK activity, the number of NK cells, and intracellular anti-cancer proteins in lymphocytes, and that this increased NK activity lasted for more than 7 days after the trip in both male and female subjects. In the present study, we investigated the effect of a day trip to a forest park on human INK activity in male subjects. Twelve healthy male subjects, aged 35-53 years, were selected after giving informed consent. The subjects experienced a day trip to a forest park in the suburbs of Tokyo. They walked for two hours in the morning and afternoon, respectively, in the forest park on Sunday. Blood and urine were sampled in the morning of the following day and 7 days after the trip, and the NK activity, numbers of NK and T cells, and granulysin, perforin, and granzyme A/B-expressing lymphocytes, the concentration of cortisol in blood samples, and the concentration of adrenaline in urine were measured. Similar measurements were made before the trip on a weekend day as the control. Phytoncide concentrations in the forest were measured. The day trip to the forest park significantly increased INK activity and the numbers of CD16(+) and CD56(+) NK cells, perforin, granulysin, and granzyme A/B-expressing NK cells and significantly decreased CD4(+) T cells, the concentrations of cortisol in the blood and adrenaline in urine. The increased INK activity lasted for 7 days after the trip. Phytoncides, such as isoprene, alpha-pinene, and beta-pinene, were detected in the forest air. These findings indicate that the day trip to the forest park also increased the NK activity, number of NK cells, and levels of intracellular anti-cancer proteins, and that this effect lasted for at least 7 days after the trip. Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL PUBLISHING, INC  

The aim of this study was to examine the association between serum insulin levels and components of the metabolic syndrome (MS). The target participants were 3054 working men. MS was diagnosed based on the modified criteria of the International Diabetes Federation and was present in 12.9% of the study patients. Serum lipid profiles, uric acid, insulin, plasma glucose, and hemoglobin A(1c) were measured. Stepwise multiple regression analysis showed that all the components of MS were significantly associated with log-transformed values of the serum insulin. The standardized regression coefficient for the waist circumference was 5-fold higher than that for fasting plasma glucose, being 0.40 and 0.08, respectively. The standardized regression coefficients for diastolic blood pressure, log-transformed values of serum triglyceride, high-density lipoprotein cholesterol, and age were 0.09, 0.13, -0.16, and -0.11, respectively. A statistically significant relationship existed between the components of MS, especially abdominal obesity, and the serum insulin levels.

DOI： 10.1111/j.1751-7176.2009.00239.x

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Objective: This study was intended to identify significant determinant factors of insulin resistance. Methods: Insulin resistance was assessed using the homeostasis model assessment for insulin resistance (HOMA-R) and was calculated as "Fasting plasma glucose × Fasting serum insulin)/405". The target subjects were 3008 working men. The serum lipid profiles, uric acid level, insulin level, plasma glucose level, hemoglobin A1C level, and blood pressure, in addition to the waist circumference or body mass index, were also measured. A stepwise multiple regression analysis was performed using log-transformed values of HOMA-R as the dependent variable. Results: The standardized regression coefficient for waist circumference was about six times larger than that for hemoglobin A1c (0.45 and 0.08, respectively). The standardized regression coefficients for the other factors were 0.15 for diastolic blood pressure, 0.10 for the low-density lipoprotein cholesterol level, -0.06 for age, -0.04 for habitual exercise, 0.14 for no habitual drinking, and 0.07 for no smoking. When body mass index was substituted for waist circumference, almost the same results were obtained. The adverse effects of no smoking and no habitual drinking on the HOMA-R score might be explained, at least in part, by the relation of these factors with obesity. Regular exercise had a protective effect on lowering insulin resistance. Conclusions: A close relation exists between obesity-related indices (waist circumference and body mass index) and insulin resistance, independent of age and other vascular risk factors in Japanese working men. © 2009 Asian Oceanian Association for the Study of Obesity.

DOI： 10.1016/j.orcp.2009.07.001

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In Japan, a forest bathing trip, called "Shinrinyoku" in Japanese, is a short, leisurely visit to a forest
it is regarded as being similar to natural aromatherapy. This review focuses on the effects of forest bathing trips on human immune function. Beginning in 2005, adult Japanese individuals, both male and female, participated in a series of studies aimed at investigating the effect of forest bathing trips on human immune function. The subjects experienced a 3-day/2-night trip to forest areas, and blood and urine were sampled on days 2 (the first sampling during each trip) and 3 (the second sampling during each trip), and on days 7 and 30 after the trips. Natural killer (NK) activity, the numbers of NK, granulysin-, perforin-, and granzymes A/B-expressing lymphocytes in the blood, and the concentration of urinary adrenaline were measured. The same measurements were made before the trips on a normal working day as a control. The mean values of NK activity and the numbers of NK, granulysin-, perforin-, and granzymes A/B-expressing cells on forest bathing days were significantly higher than those on the control days, whereas the mean values of the concentration of urinary adrenaline on forest bathing days were significantly lower than that on the control days in both male and female subjects. The increased NK activity lasted for more than 30 days after the trip, suggesting that a forest bathing trip once a month would enable individuals to maintain a higher level of NK activity. In contrast, a visit to the city as a tourist did not increase NK activity, the numbers of NK cells, or the level of intracellular granulysin, perforin, and granzymes A/B. These findings indicate that forest bathing trips resulted in an increase in NK activity, which was mediated by increases in the number of NK cells and the levels of intracellular granulysin, perforin, and granzymes A/B. © 2009 The Japanese Society for Hygiene.

DOI： 10.1007/s12199-008-0068-3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MARY ANN LIEBERT INC  

Background: The Framingham Risk Score (FRS) has frequently been used in the United States to predict the 10-year risk of coronary heart disease (CHD). Components of the metabolic syndrome and several lifestyle factors have also been evaluated to estimate the risk of CHD.
Methods: To determine the relationship between the FRS and components of metabolic syndrome as coronary risk indicators, the authors conducted a cross-sectional study of 2,619 Japanese male workers, ranging in age from 40 to 64 years, at a single workplace. Although the estimation by the FRS and metabolic syndrome involved some different factors, significant association of the risk estimated by the 2 methods was observed.
Results: When logistic regression analysis was conducted with adjustment for several lifestyle factors, the FRS and serum insulin were found to be significantly associated with the risk of likelihood of metabolic syndrome. The odds ratios and 95% confidence intervals of FRS by per standard deviation increment and serum insulin by increasing 1 mu IU/mL for the prediction of metabolic syndrome were 2.50 (2.17-2.88) and 1.24 (1.20-1.27), respectively. A preventive effect of abstaining from drinking every day and eating breakfast almost daily against the likelihood of metabolic syndrome was also observed.
Conclusions: In conclusion, the FRS and insulin were found to be significantly associated with the risk of likelihood of metabolic syndrome, even after controlling for weight change.

DOI： 10.1089/met.2008.0087

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOLIFE SAS  

We previously reported that the forest environment enhanced human natural killer (NK) cell activity, the number of NK ceIls, and intracellular anti-cancer proteins in lymphocytes, and that the increased NK activity lasted for more than 7 days after trips to forests both in male and female subjects. To explore the factors in the forest environment that activated human NK cells, in the present study we investigate the effect of essential oils from trees on human immune function in twelve healthy male subjects, age 37-60 years, who stayed at an urban hotel for 3 nights from 7.00p.m. to 8.00a.m. Aromatic volatile substances (phytoncides) were produced by vaporizing Chamaecyparis obtusa (hinoki cypress) stem oil with a humidifier in the hotel room during the night stay. Blood samples were taken on the last day and urine samples were analysed every day during the stay. NK activity, the percentages of NK and T cells, and granulysin, perforin, granzyme A/B-expressing lymphocytes in blood, and the concentrations of adrenaline and noradrenaline in urine were measured. Similar control measurements were made before the stay on a normal working day. The concentrations of phytoncides in the hotel room air were measured. Phytoncide exposure significantly increased NK activity and the percentages of NK, perforin, granulysin, and granzyme A/B-expressing cells, and significantly decreased the percentage of T cells, and the concentrations of adrenaline and noradrenaline in urine. Phytoncides, such as alpha-pinene and beta-pinene, were detected in the hotel room air. These findings indicate that phytoncide exposure and decreased stress hormone levels may partially contribute to increased NK activity.

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Background: Perceived good health or good self-rated health is considered to be a predictor of longer survival and maintenance of good quality of life, which is a public health goal. Objective: This study assessed trends in the percentage of self-rated poor health among Japanese residents, based on data from the National Comprehensive Survey of the Living Conditions of People on Health and Welfare. Methods: Results of the survey (which is conducted in Japan every 3 years to determine the living conditions of people receiving health and welfare services) were analyzed using multistage and stratified cluster sampling of households. Self-rated health was measured by response to the question, "Recently, would you say that in general your health has been good, fairly good, fair, fairly poor, or poor?" The trend in fairly poor or poor health status during the period from 1989 through 2004 was stratified by sex and age group. Results: The rates of response to the survey were 90.9% (246,892/271,588) in 1995 and 79.8% (220,836/276,682) in 2004. Target subjects were aged ≥20 years in each year of the study. The prevalence of self-reported fairly poor or poor health was lowest in 1995 and then increased every year until 2001, when it appeared to reach a plateau. The prevalence of having fairly poor or poor health among women aged 35 to 44, 45 to 54, 55 to 64, and 65 to 74 years were as follows in 1995: 9.2%, 11.7%, 15.3%, and 19.8%, respectively. In 2004, the rates were 13.3%, 17.2%, 22.1%, and 31.7%, respectively. By comparison, the prevalence of self-reported fairly poor or poor health was 8.1%, 9.3%, 13.7%, and 17.9% among men aged 35 to 44, 45 to 54, 55 to 64, and 65 to 74 years, respectively, in 1995. In 2004, these rates were 12.8%, 14.8%, 19.0%, and 27.9%, respectively. Conclusions: In this survey, conducted every 3 years between 1989 and 2004 in Japanese households, older subjects had a greater prevalence of self-reported fairly poor or poor health than did younger subjects. The proportion of respondents who described their health as poor or fairly poor was highest in 1995. Women generally had a greater prevalence of self-reported poor or fairly poor health. © 2009 Excerpta Medica Inc. All rights reserved.

DOI： 10.1016/j.genm.2009.04.001

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

It was found previously that organophosphorus pesticides (OPs) significantly inhibited cytotoxic T lymphocyte (CTL) activity. To explore the mechanism of OP-induced inhibition of CTL activity, the present study investigated whether OPs can induce cell death/apoptosis in T cells. Jurkat human T cells were treated with chlorpyrifos at 0-100 ppm for 2, 4, and 6 h at 37 degrees C in vitro. It was found that chlorpyrifos induced cell death of Jurkat human T cells in a dose- and time-dependent manner, as shown by MTT and LDH assays. Then, it was investigated if chlorpyrifos-induced cell death consisted of apoptosis, as determined by analysis of Annexin-V staining and the intracellular level of active caspase-3 by flow cytometry, and DNA fragmentation analysis. It was found that chlorpyrifos induces apoptosis in Jurkat T cells in a dose- and time-dependent manner, as determined by analysis of Annexin-V staining. DNA fragmentation was detected when cells were treated with 50 or 100 ppm chlorpyrifos for 4 and 6 h. Chlorpyrifos also induced an increase in intracellular active caspase-3 in Jurkat T cells in a dose- and time-dependent manner, and a caspase-3 inhibitor, Z-DEVD-FMK, significantly inhibited chlorpyrifos-induced apoptosis. These findings indicate that chlorpyrifos can induce apoptosis in human Jurkat T cell cells, and this effect is partially mediated by the activation of intracellular caspase-3. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.tox.2008.10.003

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki.73.22

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Other Link： http://search.jamas.or.jp/link/ui/2010054692

Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Natural killer (NK), lymphokine-activated killer (LAK), and cytotoxic T lymphocyte (CTL) cells kill target cells by the directed release of cytolytic granules that contain perforin, granzymes, and granulysin. We have found previously that dimethyl 2,2-dichlorovinyl phosphate (DDVP, dichlorvos), an organophosphorus pesticide, significantly decreased the expression of perforin, granzyme A (GrA), and granulysin and inhibited NK, LAK, and CTL activities. To further explore the mechanism of organophosphorus pesticide-induced inhibition of cell-mediated cytolysis, we examined whether organophosphorus pesticides affect the expression of GrB and Gr3/K in NK cells. We used an interleukin-2 (IL-2) independent human NK cell line, NK-92CI. We confirmed that NK-92CI cells express intracellular GrB and Gr3/K by flow cytometry, that NK-92CI cells are highly cytotoxic to K562 cells with a chromium release assay, and that DDVP significantly inhibited cytolytic activity of NK-92CI cells in a dose- and time-dependent manner. We found that DDVP significantly decreased the expression of GrB and Gr3/K in NK-92CI cells in a dose- and time-dependent manner by flow cytometry. Immunocytochemical results showed that DDVP significantly decreases the level of GrB positive granules in NK-92CI cells, which may be due to degranulation. Taken together, DDVP significantly inhibits NK activity and reduces the intracellular GrB and Gr3/K levels in NK cells. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.tox.2007.10.018

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOLIFE SAS  

We previously reported that a forest bathing trip enhanced human NK activity, number of NK cells, and intracellular anti-cancer proteins in lymphocytes. In the present study, we investigated how long the increased NK activity lasts and compared the effect of a forest bathing trip on NK activity with a trip to places in a city without forests. Twelve healthy male subjects, age 35-56 years, were selected with informed consent. The subjects experienced a three-day/two-night trip to forest fields and to a city, in which activity levels during both trips were matched. On day 1, subjects walked for two hours in the afternoon in a forest field; and on day 2, they walked for two hours in the morning and afternoon, respectively, in two different forest fields; and on day 3, the subjects finished the trip and returned to Tokyo after drawing blood samples and completing the questionnaire. Blood and urine were sampled on the second and third days during the trips, and on days 7 and 30 after the trip, and NK activity, numbers of NK and T cells, and granulysin, perforin, and granzymes A/B-expressing lymphocytes in the blood samples,, and the concentration of adrenaline in urine were measured. Similar measurements were made before the trips on a normal working day as the control. Phytoncide concentrations in forest and city air were measured. The forest bathing trip significantly increased NK activity and the numbers of NK, perforin, granulysin, and granzyme A/B-expressing cells and significantly decreased the concentration of adrenaline in urine. The increased NK activity lasted for more than 7 days after the trip. In contrast, a city tourist visit did not increase NK activity, numbers of NK cells, nor the expression of selected intracellular anti-cancer proteins, and did not decrease the concentration of adrenaline in urine. Phytoncides, such as alpha-pinene and beta-pinene were detected in forest air, but almost not in city air. These findings indicate that a forest bathing trip increased NK activity, number of NK cells, and levels of intracellular anti-cancer proteins, and that this effect lasted at least 7 days after the trip. Phytoncides released from trees and decreased stress hormone may partially contribute to the increased NK activity.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WICHTIG EDITORE  

anti-We previously reported that forest bathing trips enhanced human NK activity, number of NK cells, and intracellular anti-cancer proteins in lymphocytes, and that the increased NK activity lasted for more than 7 days after the trip in male subjects. In the present study, we investigated the effect of forest bathing trip on human NK activity in female subjects. Thirteen healthy nurses, age 25-43 years, professional career 4-18 years, were selected with informed consent. The subjects experienced a three-day/two-night trip to forest fields. On day 1, the subjects walked for two hours in the afternoon in a forest field; on day 2, they walked for two hours each in the morning and afternoon in two different forest fields; and on day 3, the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire. Blood and urine were sampled on the second and third days during the trip, and on days 7 and 30 after the trip. NK activity, numbers of NK and T cells, and granulysin, perforin, and granzymes A/B-expressing lymphocytes in the,blood samples, the concentrations of estradiol and progesterone in serum, and the concentrations of adrenaline and noradrenaline in urine were measured. Similar control measurements were made before the trip on a normal working day. The concentrations of phytoncides in the forests were measured. The forest bathing trip significantly increased NK activity and the numbers of NK, perforin, granulysin, and granzymes A/B-expressing cells and significantly decreased the percentage of T cells, and the concentrations of adrenaline and noradrenaline in urine. The increased NK activity lasted for more than 7 days after the trip. Phytoncides, such as alpha-pinene and beta-pinene were detected in forest air. These findings indicate that a forest bathing trip also increased NK activity, number of NK cells, and levels of intracellular anti-cancer proteins in female subjects, and that this effect lasted at least 7 days after the trip. Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity.

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Language：Japanese   Publisher：日本医事新報社  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

We found previously that organophosphorus pesticides (OPs) significantly inhibited natural killer (NK) activity. To explore the mechanism of OP-induced inhibition of NK activity, we investigated whether, OPs can induce apoptosis in NK cells in the present study. We used NK-92CI and NK-92MI cells, which are interleukin-2 independent human NK cell lines. NK-92CI and/or NK-92MI were treated with dichlorvos (DDVP) or chlorpyrifos (CP) at 0-100 ppm for 1-72 It at 37 degrees C in vitro. Apoptosis induced by DDVP and CP was determined by FITC-Annexin V staining and the intracellular level of active caspase-3 was analysed by flow cytometry. We found that DDVP and CP significantly induced apoptosis in NK-92CI and NK-92MI cells in a dose- and time-dependent manner. DDVP also induced an increase of intracellular active caspase-3 in NK-92CI in a dose- and time-dependent manner, and a caspase-3 inhibitor, Z-DEVD-FMK, significantly inhibited DDVP-induced apoptosis, suggesting that this apoptosis is partially mediated by activation of intracellular caspase-3. The pattern of apoptosis induced by CP differed from that induced by DDVP. CP showed a faster response than DDVP at higher doses; whereas, DDVP showed a slower, but stronger apoptosis-inducing ability than CP at lower doses. Moreover, the response to OP's differed between NK-92CI and NK-92MI cells, and NK-92CI was more sensitive to OPs than NK-92MI. This is similar to the inhibition of NK activity induced by DDVP, in which NK-92CI was more easily inhibited by DDVP than NK-92MI. Taken together, these findings suggest that OP-induced inhibition of NK activity may be at least partially mediated by OP-induced apoptosis in NK. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.tox.2007.06.100

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Organophosphorus pesticides (OPs) are widely used throughout the world as insecticides in agriculture and as eradicating agents for termites around homes. The main toxicity of OPs is neurotoxicity, which is caused by the inhibition of acetylcholinesterase. OPs also affect the immune response, including effects on antibody production, interleukin-2 production, T cell proliferation, decrease of CD5 cells, and increases of CD26 cells and autoantibodies, Th1/Th2 cytokine profiles, and the inhibition of natural killer (NK) cell, lymphokine-activated killer (LAK) cell, and cytotoxic T lymphocyte (CTL) activities. However, there have been few studies of the mechanism of OP-induced immunotoxicity, especially the mechanism of OP-induced inhibition of cytolytic activity of killer cells. This study reviews new mechanisms of OP-induced inhibition of the activities of NK cells, LAK cells, and CTLs. It has been reported that NK cells, LAK cells, and CTLs induce cell death in tumors or virus-infected target cells by two main mechanisms. The first mechanism is direct release of cytolytic granules that contain the pore-forming protein perforin, several serine proteases termed granzymes, and granulysin by exocytosis to kill target cells, which is called the granule exocytosis pathway. The second mechanism is mediated by the Fas ligand (Fas-L)/Fas pathway, in which FasL (CD95 L), a surface membrane ligand of the killer cell cross links with the target cell's surface death receptor Fas (CD95) to induce apoptosis of the target cells. To date, it has been reported that OPs inhibit NK cell, LAK cell, and CTL activities by at least the following three mechanisms: 1) OPs impair the granule exocytosis pathway of NK cells, LAK cells, and CTLs by inhibiting the activity of granzymes, and by decreasing the intracellular levels of perforin, granzyme A, and granulysin, which were mediated by inducing degranulation of NK cells and by inhibiting the transcription of the mRNAs of perforin, granzyme A, and granulysin. 2) OPs impair the FasL/Fas pathway of NK cells, LAK cells, and CTLs, as investigated by using perforin-knockout mice, in which the granule exocytosis pathway of NK cells does not function and only the FasL/Fas pathway remains functional. 3) OPs induce apoptosis of immune cells.

DOI： 10.1272/jnms.74.92

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Objective. It is well documented that natural killer (NK) cells provide host defense against tumors and viruses. We previously showed that lifestyle affects human NK and LAK activities. In order to explore the underlying mechanism, we investigated the effect of lifestyle on intracellular perforin, granulysin, and granzymes A/B in peripheral blood lymphocytes (PBL).
Methods. 114 healthy male subjects, aged 20-59 years, from a large company in Osaka, Japan were selected with informed consent. The subjects were divided into groups reporting good, moderate, and poor lifestyles according to their responses on a questionnaire regarding eight health practices (cigarette smoking, alcohol consumption, sleeping hours, working hours, physical exercise, eating breakfast, balanced nutrition, and mental stress). Peripheral blood was taken, and numbers of NK, T, perform, granulysin, and granzymes A/B-expressing cells in PBL were measured by flow cytometry.
Results. Subjects with good or moderate lifestyle showed significantly higher numbers of NK, and perform, granulysin, and granzymes A/B-expressing cells and a significantly lower number of T cells in PBL than subjects with poor lifestyle. Among the eight health practices, cigarette smoking, physical exercise, eating breakfast, and balanced nutrition significantly affect the numbers of NK, T cells, perform, granulysin, and/or granzymes A/B-expressing cells, and alcohol consumption significantly affects the number of granzyme A-expressing cells. On the other hand, mental stress, sleeping, and working hours had no effect on those parameters.
Conclusions. Taken together, these findings indicate that poor lifestyle significantly decreases the numbers of NK, perforin, granulysin, and granzymes A/B-expressing cells in PBL. (c) 2006 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ypmed.2006.08.017

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In order to explore the effect of forest bathing on human immune function, we investigated natural killer (NK) activity; the number of NK cells, and perforin, granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields. Twelve healthy male subjects, age 37-55 years, were selected with informed consent from three large companies in Tokyo, Japan. The subjects experienced a three-day/two-night trip in three different forest fields. On the first day, subjects walked for two hours in the afternoon in a forest field; and on the second day, they walked for two hours in the morning and afternoon, respectively, in two different forest fields. Blood was sampled on the second and third days, and NK activity; proportions of NK, T cells, granulysin, perforin, and granzymes A/B-expressing cells in PBL were measured. Similar measurements were made before the trip on a normal working day as the control. Almost all of the subjects (11/12) showed higher NK activity after the trip (about 50 percent increased) compared with before. There are significant differences both before and after the trip and between days 1 and 2 in NK activity. The forest bathing trip also significantly increased the numbers of NK, perforin, granulysin, and granzymes A/B-expressing cells. Taken together, these findings indicate that a forest bathing trip can increase NK activity, and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins.

DOI： 10.1177/03946320070200s202

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

In order to investigate chlorpyrifos-induced cell death and its underlying mechanism in human immune cells, a human monocyte like cell line (U937) was treated with chlorpyrifos at 4.45-570 mu M for 0.5-24 h at 37 degrees C in a 5% CO2 incubator. We first found that chlorpyrifos induced cell death of U937 in a dose- and time-dependent manner,,as shown by LDH and MTT assays and PI uptake. Then, we investigated if chlorpyrifos-induced cell death consisted of apoptosis, as determined by analysis of Annexin-V staining and the intracellular level of active caspase-3 by flow cytometry, and DNA fragmentation analysis. We found that chlorpyrifos induced apoptosis in U937 in a time- and dose-dependent manner, as shown by Annexin-V staining. DNA fragmentation was detected when cells were treated with 71 to 284 mu M chlorpyrifos for 4 or 6 It. Chlorpyrifos also induced an increase of intracellular active caspase-3 in U937 cells in a dose-dependent manner, and a caspase-3 inhibitor, Z-DEVD-FMK, significantly inhibited the chlorpyrifos-induced apoptosis. These findings indicate that chlorpyrifos can induce apoptosis in U937 cells, and this effect is partially mediated by activation of intracellular caspase-3. (c) 2006 Published by Elsevier Ireland Ltd.

DOI： 10.1016/j.tox.2006.04.055

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHIN SOCIETY IMMUNOLOGY  

The main toxicity of organophosphorus pesticides (OPs) is neurotoxicity, which is caused by the inhibition of acetylcholinesterase. OPs also affect immune responses including effects on antibody production, IL-2 production, T cell proliferation, decreasement of CD5 cells, and increasement of CD26 cells and autoantibodies. However, there have been few papers investigating the mechanism of OP-induced inhibition of cytolytic activity of killer cells. This study reviews the new mechanism of OP-induced inhibition of activities of natural killer (NK), lymphokine-activated killer (LAK) and cytotoxic T lymphocytes (CTL). NK, LAK and CTL induce cell death in tumor or virus-infected target cells by two main mechanisms. The first mechanism is direct release of cytolytic granules that contain perforin, granzymes, and granulysin by exocytosis to kill target cells, which is called the granule exocytosis pathway. The second mechanism is mediated by the Fas ligand (Fas-L)/Fas pathway. To date, it has been reported that OPs inhibit NK, LAK and CTL activities by at least the following three mechanisms: 1) OPs impair the granule exocytosis pathway of NK, LAK and CTL cells by inhibiting the activity of granzymes, and by decreasing the intracellular level of perforin, granzyme A and granulysin, which was mediated by inducing degranulation of NK cells and by inhibiting the transcript of mRNA of perforin, granzyme A and granulysin; 2) OPs impair the FasL/Fas pathway of NK, LAK and CTL cells, as investigated by using perforin-knockout mice, in which the granule exocytosis pathway of NK cells does not function and only the FasL/Fas pathway remains functional; 3) OPs induce apoptosis of immune cells.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS INC  

To explore the effect of forest bathing on the human immune system, we investigated the effect of phytoncides (wood essential oils) on natural killer (NK) activity and the expression of perforin, granzyme A and granulysin in human NK cells. We used NK-92MI cell, an interleukin-2 independent human NK cell line derived from the NK-92 cell, in the present study. NK-92MI cells express the CD56 surface marker, perforin, granzyme A, and granulysin by flow cytometry and are highly cytotoxic to K562 cells in chromium release assay. Phytoncides significantly increase cytolytic activity of NK-92MI cells in a dose-dependent manner and significantly increase the expression of perforin, granzyme A, and granulysin in the NK-92MI cells. Phytoncides also partially, but significantly, restore the decreased human NK activity and the decreased perforin, granzyme A, and granulysin expression in NK-92MI cells induced by dimethyl 2,2-dichlorovinyl phosphate ( DDVP), an organophosphorus pesticide. Pretreatment with phytoncides partially prevents DDVP-induced inhibition of NK activity. Taken together, these data indicate that phytoncides significantly enhance human NK activity and this effect is at least partially mediated by induction of intracellular perforin, granzyme A, and granulysin.

DOI： 10.1080/08923970600809439

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Human granzyme 3 (Gr3) is a serine protease contained in the granules of natural killer cells and cytotoxic T lymphocytes. To elucidate the biochemical and physiological characteristics of Gr3, we attempted to prepare an enzymatically active recombinant human Gr3 without refolding and proteolytic activation. An expression vector was constructed, in which the pre-/pro-peptide coding sequence of Gr3 was replaced with the bacterial pelB leader sequence. The resultant expression product was a fully active protease in the periplasmic fraction of Escherichia coli and was purified to homogeneity. The purified enzyme effectively hydrolyzed Z-Lys-SBzl, a conventionally used substrate of GO. In addition, it also hydrolyzed the peptide substrate library FRETS-25Xaa series, required basic amino acid residues, Arg or Lys, at the PI position, and most efficiently hydrolyzed the carboxylic side of Phe-Tyr-Arg down arrow (P3-P2-P1) sequence of the 475 tripeptide combinations. (c) 2005 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.abb.2005.12.001

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Language：Japanese   Publisher：日本森林技術協会  

CiNii Books

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Language：Japanese   Publisher：Japan Society for Occupational Health  

DOI： 10.1539/sangyoeisei.KJ00004429345

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2008222630

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Natural killer (NK), lymphokine-activated killer (LAK) and cytotoxic T lymphocyte (CTL) cells kill target cells by the directed release of cytolytic granules that contain perforin, granzymes and granulysin. We previously have found that dimethyl 2,2-dichlorovinyl phosphate (DDVP), an organophosphorus pesticide significantly inhibited NK, LAK and CTL activities via the inhibition of granzyme activity. To further explore the mechanism of organophosphorus pesticide-induced inhibition of cell-mediated cytolysis, we asked here whether organophosphorus pesticides affect the expression of perforin, granzyme and granulysin in NK cells. We used NK-92CI cell, an interleukin-2 (IL-2) independent human NK cell line. We confirmed that NK-92CI cells express CD56 surface marker, perform, granzyme A and granulysin by flow cytometry and immunofluorescence microscope, and that it is highly cytotoxic to K562 cells in chromium release assay. We found that DDVP significantly decreases the expression of perform, granzyme A and granulysin in NK-92CI cells in a dose-dependent manner. Immunocytochemical results showed that DDVP significantly decreases perforin, granzyme A and granulysin positive granules in NK-92CI cell, which may be due to the degranulation. We also found that DDVP have a modest, but a significant inhibitory effect on the transcription of mRNA of perform, granzyme A and granulysin. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.tox.2005.05.018

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

To explore the mechanism of stress-induced inhibition of natural killer (NK) activity, female C57BL/6 mice were stimulated by electric foot shock and psychological stress for 7 days consecutively. The shocked mice received scrambled, uncontrollable, inescapable 0.6 mA electric shocks in a communication box 120 times during 60 min. The mice in the psychological stress group were put into the communication box without electric foot shock. The plasma corticosterone level in both stressed groups was significantly higher than that in controls on days 1, 3, 5 and 7 and showed the highest level on day 3 in the foot shock stress. According to these results, therefore, we investigated the effect of stress on immunological function on day 3, and measured body weight, weight of the spleen, number of splenocytes, splenic NK, lymphokine-activated killer (LAK) and cytotoxic T lymphocyte (CTL) activities, NK receptors, and mRNA transcripts for granzymes A and B and perforin in splenocytes. The NK, LAK and CTL activities, and NK receptors in mice with both types of stress were significantly decreased compared to those of the control mice, but the decreases were greater in the foot-shocked mice than in the psychological-stress mice. The mRNA transcripts for granzyme A and perforin were significantly decreased only in the foot-shocked mice. On the other hand, the foot-shock stress increased granzyme B. The above findings suggest that stress induced inhibition of NK, LAK and CTL activities partially via affecting NK receptors, granzymes and perforin.

DOI： 10.1080/10253890500140972

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERCEPTUAL MOTOR SKILLS  

More than 5,000 passengers on Tokyo subway trains were injured with toxic chemicals including the nerve gas "sarin" on March 20, 1995. The purpose of this study was to identify the effect of satin exposure on insomnia in a cross-sectional study. A self-administered questionnaire concerning sleep-related items was distributed to victims of sarin exposure in October and November, 2003. Questionnaires were completed by 161 of the 163 participants (98.8%), who were selected from 1,500 subjects. Among them, the authors selected 75 women 30 to 69 years of age. Control participants were collected from inhabitants living in Maebachi City, Gunma Prefecture, Japan. For the younger exposed group (under 50 yr. of age), percentages of poor sleep, difficulty falling asleep, intermittent awakening, early morning awakening, a feeling of light overnight sleep, and insomnia were significantly higher than those for the control group. In contrast, the older exposed group (ages 50 to 69 years) had significantly higher prevalence of poor sleep, a feeling of light overnight sleep, and early morning awakening for the exposed group when compared with the control group. The high prevalence of insomnia and insomnia-related factors for victims especially under 50 years of age suggests a need for research on sleep quality after satin exposure. Although posttraumatic stress disorder is assumed to be a psychological effect of exposure to a toxic substance, a cause-and-effect relationship has not been established.

DOI： 10.2466/pms.100.3c.1121-1126

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC IMMUNOLOGISTS  

Granulysin, a cationic protein produced by activated human CTL and NK cells, is cytolytic against microbial and tumor targets. In this study we show that granulysin also functions as a chemoattractant and activates monocytes to produce cytokines/chemokines. Although granulysin-mediated cytotoxicity occurs at micromolar concentrations, chemoattraction occurs in the nanomolar range, and immune activation occurs over a wide range of concentrations (nanomolar to micromolar). Granulysin causes a 2- to 7-fold increase in chemotaxis of monocytes, CD4(+), and CD8(+) memory (CD45RO) but not naive (CD45RA) T cells, NK cells, and mature, but not immature, monocyte-derived dendritic cells. Pertussis toxin treatment abrogates chemoattraction by granulysin, indicating involvement of G-protein-coupled receptor(s). At low concentrations (10 nM), granulysin promotes a 3- to 10-fold increase in MCP-1 and RANTES produced by monocytes and U937 cells, while a 2-fold increase in TNF-alpha production by LPS-stimulated monocytes requires higher concentrations of granulysin (micromolar). Taken together, these data indicate that the local concentration of granulysin is critical for the biologic activity, with high concentrations resulting in cytotoxicity while lower concentrations, presumably further from the site of granulysin release, actively recruit immune cells to sites of inflammation.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC HEMATOLOGY  

Delivery of biologically active peptides into cells may help elucidate intracellular signal transduction pathways, identify additional in vivo functions, and develop new therapeutics. Although p21 was first identified as a major regulator of cell cycle progression, it is now clear that p21 subserves multiple functions. The amino terminus of p21 interacts with cyclins and cyclin-dependent kinases, while the carboxyl terminus interacts with proliferating cell nuclear antigen (PCNA), growth arrest and DNA damage-inducible gene 45 (GADD45), calmodulin, SET, and CCAAT/enhancer binding protein-alpha (C/EBP-alpha). A chimeric peptide, p21-IRS, consisting of the carboxyl terminal domain of p21 conjugated to a pentapeptide (RYIRS) rapidly enters lymphoid cells and activates apoptosis. In the present study, we investigate the molecular events involved in p21-activated apoptosis. Comparison of p21-IRS with other known proapoptotic agents demonstrates that p21-IRS activates a novel apoptotic pathway: mitochondria are central to the process, but caspases and a decrease in DeltaPsi(m) are not involved. Targeting the p21 peptide to specific cell populations may allow development of novel therapies to eliminate aberrant cells in human diseases. (C) 2005 by The American Society of Hematology.

DOI： 10.1182/blood-2004-06-2188

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC MICROBIOLOGY  

Grarmlysin, a 9-kDa protein localized in human cytollytic T lymphoctyes and natural killer cell granules, is cytollytic against tumors and microbes but not against red blood cells. Synthetic peptides corresponding to the central region of granulysin recapitulate the lytic activity of the intact molecule, and some peptides cause hemolysis of red blood cells. Peptides in which cysteine residues were replaced by serine maintain their activity against microbes but lose activity against human cells, suggesting their potential as antibiotics. Studies were undertaken to determine the mechanism of resistance of red blood cells to granulysin and sensitivity to a subset of granulysin-derived peptides. Granulysin lyses immature reticulocytes, which have mitochondria, but not red blood cells. Granulysin lyses U937 cells but not U937 cells lacking mitochondrial DNA and a functional respiratory chain (U937rhodegrees cells), further demonstrating the requirement of intact mitochondria for granulysin-mediated death. Peptide G8, which corresponds to helix 2/loop 2/helix 3, lyses red blood cells, while peptide G9, which is identical except that the cysteine residues were replaced by serine, does not lyse red blood cells. Granulysin peptide-induced hemolysis is markedly inhibited by an anion transporter inhibitor and by Na+, K+, and Ca2+ channel blockers but not by Na+/K+ pump, cotransport, or Cl- channel blockers. Although recombinant granulysin and G9 peptide do not induce hemolysis, they both competitively inhibit G8-induced hemollysis. The finding that some derivatives of granulysin are hemolytic may have important implications for the design of granulysin-based antimicrobial therapeutics.

DOI： 10.1128/AAC.49.1.388-397.2005

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Language：Japanese   Publisher：公益社団法人 日本産業衛生学会  

DOI： 10.1539/sangyoeisei.KJ00003804039

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Language：Japanese   Publisher：公益社団法人 日本産業衛生学会  

DOI： 10.1539/sangyoeisei.KJ00003804040

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Language：English   Publishing type：Research paper (scientific journal)  

A promoter region of human mercaptopyruvate sulfurtransferase (MST) [EC 2.8.1.2] is G+C-rich and TATA-less, showing features of a house-keeping gene. In the core promoter, a GC box (-284:GGGGCGTGGC:-275) and an initiator (-219:TTATATG:-225) are found. A cap site hunting analysis for human liver cDNA revealed four possible transcriptional start sites, nucleotides -223, -159, -35 and -25. Point mutagenesis and deletion studies suggest that a module of the silencer element is -394:GCTG:-391. A replacement of -391G to C lost the silencer function; on the other hand, a replacement of -394G to T or C, -393C to T or -392T to G markedly reduced the promoter activity.

PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI IRELAND LTD  

Natural killer (NK), lymphokine-activated killer (LAK) and cytotoxic T lymphocyte (CTL) cells induce target cell death by two main mechanisms, the perforin/granzyme pathway and the Fas-ligand (FasL)/Fas pathway. We have previously found that organophosphorus pesticides significantly inhibit human and murine NK, LAK and CTL activities and that this inhibition is partially mediated by the inhibition of granzymes. We asked here whether organophosphorus pesticides also affect the FasL/Fas pathway by using perforin-knockout (PKO) mice. Thus, we examined the effect that dimethyl 2,2-dichlorovinyl phosphate (DDVP), an organophosphorus pesticide has on NK, CTL and LAK activities of PKO mice in vitro using the Fas antigen-positive YAC-1 cell as a target in the present study. We found that DDVP significantly decreased NK, CTL and LAK activities in a dose-dependent manner, and that the CTL and LAK activities of PKO mice were significantly blocked by anti-FasL antibody, suggesting that DDVP and anti-FasL antibody have the same/similar mechanism of inhibiting LAK and CTL activities. We further found that DDVP decreases the expression of Fas antigen on YAC-1 cells, and the expression of FasL on LAK cells in a dose-dependent manner, respectively. Taken together, these findings indicate that the DDVP-induced inhibition of NK, LAK and CTL activities in PKO mice is mediated by the impairment of the FasL/Fas pathway. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.tox.2004.05.019

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

A promoter region of human mercaptopyruvate sulfurtransferase (MST) [EC 2.8.1.2] is G+C-rich and TATA-less, showing features of a house-keeping gene. In the core promoter, a GC box (-284:GGGGCGTGGC:-275) and an initiator (-219:TTATATG:-225) are found. A cap site hunting analysis for human liver cDNA revealed four possible transcriptional start sites, nucleotides -223, -159, -35 and -25. Point mutagenesis and deletion studies suggest that a module of the silencer element is -394:GCTG:-391. A replacement of -391G to C lost the silencer function; on the other hand, a replacement of -394G to T or C, -393C to T or -392T to G markedly reduced the promoter activity. (C) 2004 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.bbaexp.2004.09.007

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

We previously reported that the frequency of sister chromatid exchanges (SCEs) among victims of the Tokyo subway satin disaster was significantly higher than that of controls 2-3 months after the disaster. It has been reported that the victims were also exposed to the by-products generated during sarin synthesis, i.e., diisopropyl methylphosphonate (DIMP), diethyl methylphosphonate (DEMP) and NN-diethylaniline (DEA) during the disaster and we previously found that DIMP, DEMP and DEA induced a significant SCE increase in human lymphocytes in vitro. To monitor the genetic aftereffects of the sarin exposure, SCEs of peripheral blood lymphocytes were measured in fire fighters and police officers involved in the disaster 3 years after the event. We found that the frequency of SCEs was still significantly higher in the exposed subjects than the controls, suggesting a risk of the genetic aftereffects of the sarin exposure. We further found a significant positive correlation between the frequency of SCEs and the inhibition of serum cholinesterase activity in the exposed subjects, suggesting that the elevated frequency of SCEs is related to the sarin exposure. On the other hand, there was no significant difference in natural killer activity between the exposed and the controls. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.tox.2004.04.014

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC IMMUNOLOGISTS  

Granulysin, a molecule present in the granules of CTL and NK cells, is cytolytic against microbes and tumors. Granulysin induces apoptosis of mammalian cells by damaging mitochondria and causing the release of cytochrome c and apoptosis-inducing factor, resulting in DNA fragmentation. Here we show that Ca2+ and K+ channels as well as reactive oxygen species are involved in granulysin-mediated Jurkat cell death. The Ca2+ channel blockers, nickel and econazole, and the K+ channel blockers, tetraethylammonium chloride, apamin, and charybdotoxin, inhibit the granulysin-induced increase in intracellular Ca2+ ([Ca2+](i)), the decrease in intracellular K+, and apoptosis. Thapsigargin, which releases Ca2+ from the endoplasmic reticulum, prevents a subsequent granulysin-induced increase in [Ca2+](i) in Jurkat cells, indicating that the initial increase in [Ca2+](i) is from intracellular stores. The rise in [Ca2+](i) precedes a decrease in intracellular K+, and elevated extracellular K+ prevents granulysin-mediated cell death. In granulysin-treated cells, electron transport is uncoupled, and reactive oxygen species are generated. Finally, an increase in intracellular glutathione protects target cells from granulysin-induced lysis, indicating the importance of the redox state in granulysin-mediated cell death.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：C A B I PUBLISHING  

Epidemic spastic paraparesis (konzo) found in tropical and subtropical countries is known to be caused by long-term intake of cassava (Manihot esculenta Crantz), which contains a cyanoglucoside linamarin (alpha-hydroxyisobutyronitrile-beta-D-glucopyranoside). It has been reported that linamarin is enzymatically converted to cyanide by bacteria in the intestine, and this is absorbed into the blood and then damages neural cells. However, unmetabolized linamarin was found in the urine after oral administration of cassava; thus, we hypothesized that konzo could be caused by direct toxicity of the unmetabolized linamarin that was transferred to the brain and could be transported into neural cells via a glucose transporter. In the present study it was confirmed that linamarin directly damaged neural culture pheochromocytoma cell (PC) 12 cells; 0.10 mM-linamarin caused cell death at 13.31 (SD 2.07)%, which was significantly different from that of control group (3.18 (SD 0.92)%, P=0.0004). Additional 10 mum-cytochalasin B, an inhibitor of a glucose transporter, prevented cell death: the percentage of dead cells significantly decreased to 6.06 (SD 1.98), P=0.0088). Furthermore, glucose also prevented cell death. These present results strongly suggest that linamarin competes with cytochalasin B and glucose for binding to a glucose transporter and enters into cells via glucose transporter.

DOI： 10.1079/BJN2003902

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Language：English   Publishing type：Research paper (scientific journal)  

A well-known combined therapy for acute cyanide poisoning is intravenous administration of sodium nitrite, sodium thiosulfate and cobalt EDTA. Sodium nitrite oxidizes oxy-hemoglobin, resulting in methemoglobin, which has a high affinity for cyanide. Sodium thiosulfate is a substrate of thiosulfate: cyanide sulfurtransferase (rhodanese, EC.2.8.1.1), and facilitates catalytic metabolism of cyanide to less toxic thiocyanate. Cobalt EDTA combines with cyanide to reduce cyanide in the blood. Here, we focus on cytosolic and mitochondrial mercaptopyruvate sulfurtransferase (MST, EC. 2.8.1.2), which detoxifies cyanide more effectively than rhodanese, because rhodanese is localized only in mitochondria. Thiosulfate also serves as a substrate of MST and cyanide can be metabolized to thiocyanate. However, the K(m) value for thiosulfate is so large that it is not expected to contribute much to the detoxification of cyanide. On the other hand, nitrite and cobalt EDTA did not affect MST. Thus, combined therapy only slightly acts on MST to detoxify cyanide. Some investigators have attempted a new therapy in which mercaptopyruvate, a substrate of MST was administered intravenously, but this was not effective for detoxification due to the rapid decomposition of mercaptopyruvate in the blood. There are two possible strategies to facilitate MST activities: development of modified mercaptopyruvate with a longer half time and development of a chemical compound which indirectly increases transcription of MST via regulation of a DNA binding protein.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC OCCUPATIONAL HEALTH  

DOI： 10.1539/joh.44.264

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC OCCUPATIONAL HEALTH  

DOI： 10.1539/joh.44.264

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI IRELAND LTD  

We have previously found that diisopropyl methylphosphonate, an organophosphorus by-product generated during sarin synthesis in the Tokyo sarin disaster, significantly inhibited natural killer (NK) and cytotoxic T lymphocyte (CTL) activities. In the present study, to investigate whether organophosphorus pesticides (OPs) also affect NK and CTL activities, we firstly examined the effect of five OPs on human NK activity, and then the effect of Dimethyl 2,2-dichlorovinyl phosphate (DDVP), an OP on murine splenic NK, CTL and lymphokine-activated killer (LAK), and human LAK activities in vitro. To explore the underlying mechanism of decreased NK activity, we also investigated the effect of 4-(2-aminoethyl) benzenesulfonyl fluoride-HCl (p-ABSF), an inhibitor of serine proteases oil NK, LAK and CTL activities, and the effect of DDVP on the activity of granzymes (serine proteases). We found that OPs significantly decreased human NK activity in a dose-dependent manner, but the degree of decrease in NK activity differed among the OF's investigated, and that DDVP significantly decreased NK, LAK and CTL activities in a dose-dependent manner, but the degree of decrease in these activities differed. p-ABSF showed a similar inhibitory pattern to DDVP, and had an additive inhibitory effect with DDVP on NK, LAK and CTL activities. We also found that DDVP significantly inhibited granzyme activity in a dose-dependent manner. These findings indicate that OPs significantly decrease NK, LAK and CTL activities in vitro via granzyme inhibition. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0300-483X(02)00004-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI IRELAND LTD  

We have previously found that diisopropyl methylphosphonate, an organophosphorus by-product generated during sarin synthesis in the Tokyo sarin disaster, significantly inhibited natural killer (NK) and cytotoxic T lymphocyte (CTL) activities. In the present study, to investigate whether organophosphorus pesticides (OPs) also affect NK and CTL activities, we firstly examined the effect of five OPs on human NK activity, and then the effect of Dimethyl 2,2-dichlorovinyl phosphate (DDVP), an OP on murine splenic NK, CTL and lymphokine-activated killer (LAK), and human LAK activities in vitro. To explore the underlying mechanism of decreased NK activity, we also investigated the effect of 4-(2-aminoethyl) benzenesulfonyl fluoride-HCl (p-ABSF), an inhibitor of serine proteases oil NK, LAK and CTL activities, and the effect of DDVP on the activity of granzymes (serine proteases). We found that OPs significantly decreased human NK activity in a dose-dependent manner, but the degree of decrease in NK activity differed among the OF's investigated, and that DDVP significantly decreased NK, LAK and CTL activities in a dose-dependent manner, but the degree of decrease in these activities differed. p-ABSF showed a similar inhibitory pattern to DDVP, and had an additive inhibitory effect with DDVP on NK, LAK and CTL activities. We also found that DDVP significantly inhibited granzyme activity in a dose-dependent manner. These findings indicate that OPs significantly decrease NK, LAK and CTL activities in vitro via granzyme inhibition. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0300-483X(02)00004-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI IRELAND LTD  

We previously found that N,N-diethylaniline increased the frequency of sister chromatid exchange (SCE) of human lymphocytes to about five times that of the control value, and was as toxic as cyclophosphamide used as a positive control for SCE. To explore whether N,N-diethylaniline affects the function of lymphocytes, we evaluated its immunotoxicity using CBA/N mice. The mice were divided into four groups and received 0, 100, 200, or 400 mg/kg body weight of N,N-diethylaniline by subcutaneous injection. The following items were investigated on days 3 and 7 after injection: body weight, weight of spleen, number of splenocytes, natural killer (NK) and cytotoxic T lymphocyte (CTL) activities, and concanavalin A (Con A)- and lipopolysaccharide (LPS)-stimulated lymphocyte proliferation using splenocytes. The following splenocyte phenotypes were also quantified by flow cytometry: (1) B cells; (2) total T cells; (3) CD4(+) and CD8(+) T cells; (4) NK; (5) macrophages and (6) nucleated erythrocytes. The splenic NK and CTL activities in exposed groups significantly decreased compared to the control in a dose-dependent manner and lymphocytes from the 200 and 400 mg/kg groups showed significantly higher spontaneous proliferation. The weight of the spleen and number of splenocytes were significantly higher in exposed groups than in the control. N,N-Diethylaniline also increased the percentages of macrophages, nucleated erythrocytes and B cells in the spleen. On the other hand, N,N-diethylaniline did not affect LPS-stimulated B cell and Con A-stimulated T cell proliferation, or the percentages of NK, total T, and CD4(+) and CD8(+) T cells in the spleen or the body weight of mice. The above findings indicated that N,N-diethylaniline selectively inhibited splenic NK and CTL activity and this inhibition was due to decreased NK and CTL functions, but not due to changes in the numbers of splenic NK and T cells. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0300-483X(00)00247-X

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More than 5000 passengers on Tokyo subway trains were injured by the nerve gas, sarin and its by-products. Analysis of phosphor-carrying metabolites of sarin and its by-products in urine samples from the victims suggested that they were exposed not only to sarin, but also by-products generated during sarin synthesis, i.e. diisopropyl methylphosphonate (DIMP) and diethyl methylphosphonate (DEMP). We suspected genetic after-effects due to sarin by-products, thus, we checked the frequency of sister chromatid exchange (SCE) and found that SCE was significantly higher in the victims than in a control group, and that DIMP and DEMP significantly induced human lymphocyte SCE in vitro. In the present study, to explore whether DIMP and DEMP, which induced a high frequency of SCE of lymphocytes, also affected the lymphocyte functions, we examined the effect of DIMP and DEMP on splenic natural killer (NK) and splenic cytotoxic T lymphocyte (CTL) activity in mice, and NK activity of human lymphocytes in vitro. We found that DIMP and DEMP significantly inhibited NK and CTL activity in a dose-dependent manner. The inhibition induced by DIMP was stronger than that by DEMP. The effect of DIMP and DEMP on the splenic NK activity of mice was stronger than on the splenic CTL activity, and the human lymphocytes is more sensitive to DIMP and DEMP than the splenocytes of mice. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0300-483X(00)00174-8

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI IRELAND LTD  

To evaluate the immunotoxicity of p-chloronitrobenzene (p-CNB), we investigated its effect on the immunophenotype of murine splenocytes. BDF1 male mice were randomly divided into exposed and control groups: the exposed group received p-CNB at 300 mg/kg dissolved in olive oil, while the control group received only olive oil, by a single intraperitoneal (ip) or subcutaneous (sc) injection. On days 3, 5, 7, and 10 after the injection, splenocytes were harvested from both groups, and the following cell phenotypes were quantified by flow cytometry: (1) B cells (CD45R/B220); (2) T cells (CD3e); (3) T-cell subsets (CD4 and CD8a); (4) natural killer (NK) cells (NK-1.1); (5) macrophages (CD11b; Mac-1); (6) nucleated erythrocytes (Ter-119); and (7) dead cells with propidium iodide (PI). The percentages and numbers of B, T, subsets of T (CD4 and CD8), and NK cells in the exposed mice significantly decreased as compared with the respective control. On the other hand, macrophages (Mac-1(+) cells), nucleated erythrocytes (Ter-119(+) cells), and dead cells in the exposed mice markedly increased as compared with the respective control after ip injection of p-CNB. The above findings indicate that p-CNB has an immunotoxic effect on mice. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0300-483X(99)00065-7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI IRELAND LTD  

To evaluate the immunotoxicity of p-chloronitrobenzene (p-CNB), we investigated its effect on the immunophenotype of murine splenocytes. BDF1 male mice were randomly divided into exposed and control groups: the exposed group received p-CNB at 300 mg/kg dissolved in olive oil, while the control group received only olive oil, by a single intraperitoneal (ip) or subcutaneous (sc) injection. On days 3, 5, 7, and 10 after the injection, splenocytes were harvested from both groups, and the following cell phenotypes were quantified by flow cytometry: (1) B cells (CD45R/B220); (2) T cells (CD3e); (3) T-cell subsets (CD4 and CD8a); (4) natural killer (NK) cells (NK-1.1); (5) macrophages (CD11b; Mac-1); (6) nucleated erythrocytes (Ter-119); and (7) dead cells with propidium iodide (PI). The percentages and numbers of B, T, subsets of T (CD4 and CD8), and NK cells in the exposed mice significantly decreased as compared with the respective control. On the other hand, macrophages (Mac-1(+) cells), nucleated erythrocytes (Ter-119(+) cells), and dead cells in the exposed mice markedly increased as compared with the respective control after ip injection of p-CNB. The above findings indicate that p-CNB has an immunotoxic effect on mice. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0300-483X(99)00065-7

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DOI： 10.1016/S0300-483X(98)00131-0

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Language：Japanese   Publisher：Japan Society for Occupational Health  

DOI： 10.1539/sangyoeisei.KJ00001991421

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Other Link： http://search.jamas.or.jp/link/ui/1999116644

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CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/1999116644

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI IRELAND LTD  

More than 5000 passengers of Tokyo subway trains were injured with toxic chemicals including the nerve gas sarin. Most of the victims examined had marked miosis and decreased serum cholinesterase activity. To monitor the genetic aftereffects of sarin exposure, we measured sister chromatid exchanges (SCEs) of the victims using peripheral blood lymphocytes. The frequency of SCEs was significantly higher in the victims than in the control group. Analyzing results using samples of urine from the victims suggested that the victims were exposed to not only sarin per se, but by-products of sarin synthesis, i,e. diisopropyl methylphosphonate (DIMP), diethyl methylphosphonate (DEMP) and ethyl isopropyl methylphosphonate (EIMP). Thus, the in vitro SCE-inducing effect of DIMP, DEMP and EIMP was examined using human lymphocytes and we obtained positive results. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0378-4274(98)00108-8

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We evaluated the immunotoxicity of p-chloronitrobenzene (p-CNB) after intraperitoneal (ip) injection of p-CNB in BDF1 mice; single ip injection of 300 mg/kg (acute experiments), or 30 mg/kg three times a week for 4 weeks (subchronic experiments).The following items were investigated: number of splenocytes, natural killer (NK) activity, cytotoxic T-lymphocyte (CTL) activity and LPS-stimulated lymphocyte proliferation using splenocytes, hemoglobin (Hb) concentration in peripheral blood and body weight. NK activity in exposed mice significantly decreased compared to control in both acute and subchronic experiments. CTL activity in acute exposed mice showed a significant decrease on the 3rd day only after injection, and significant decrease at 3 and 4 weeks in subchronic exposed mice compared to controls. Comparing the effect of p-CNB on NK activity with that of CTL for both the acute and subchronic exposures, NK activity was more inhibited by p-CNB than CTL activity in the acute stage, whereas both the NK and CTL activities were inhibited by p-CNB in the subchronic stage. There was an indication that p-CNB also inhibited LPS- stimulated B-lymphocyte proliferation. On the other hand, Hb concentration did not show significant difference between the exposed and control mice in both acute and subchronic experiments. Body weight in subchronically exposed mice was significantly lower than the control from day 19. The above evidence indicated that p-CNB has an inherent immunotoxic effect on mice. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI IRELAND LTD  

We evaluated the immunotoxicity of p-chloronitrobenzene (p-CNB) after intraperitoneal (ip) injection of p-CNB in BDF1 mice; single ip injection of 300 mg/kg (acute experiments), or 30 mg/kg three times a week for 4 weeks (subchronic experiments).The following items were investigated: number of splenocytes, natural killer (NK) activity, cytotoxic T-lymphocyte (CTL) activity and LPS-stimulated lymphocyte proliferation using splenocytes, hemoglobin (Hb) concentration in peripheral blood and body weight. NK activity in exposed mice significantly decreased compared to control in both acute and subchronic experiments. CTL activity in acute exposed mice showed a significant decrease on the 3rd day only after injection, and significant decrease at 3 and 4 weeks in subchronic exposed mice compared to controls. Comparing the effect of p-CNB on NK activity with that of CTL for both the acute and subchronic exposures, NK activity was more inhibited by p-CNB than CTL activity in the acute stage, whereas both the NK and CTL activities were inhibited by p-CNB in the subchronic stage. There was an indication that p-CNB also inhibited LPS- stimulated B-lymphocyte proliferation. On the other hand, Hb concentration did not show significant difference between the exposed and control mice in both acute and subchronic experiments. Body weight in subchronically exposed mice was significantly lower than the control from day 19. The above evidence indicated that p-CNB has an inherent immunotoxic effect on mice. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0300-483X(98)00027-4

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Language：Japanese   Publisher：Japan Society for Occupational Health  

DOI： 10.1539/sangyoeisei.KJ00001990222

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Toxicology  

More than 20,000 passengers of Tokyo underground trains were intoxicated with warfare toxic chemicals. Most of the patients examined had marked miosis and decreased serum cholinesterase activity. Transient increase of serum CDK activity after 3 days of the exposure was the another sign. We intensively analyzed the metabolites in the urine of 4 patients. The following analytic results indicated the exposure to sarin as well as contaminated compounds such as diisopropyl methylphosphonate (DIMP), ethyl methylphosphonate fluoridate (EMPF, or ethylsarin), diethyl methylphosphonate (DEMP), and ethyl isopropyl methylphosphonate (EIMP). (1) Isopropanol (IPA) and ethanol (EtOH) were detected of large quantities in the urine samples, and were thought to be derived from sarin and the sarin counterpart, EMPF, DIMP, DEMP and EIMP. (2) Monoalkyl methylphosphonic acids (isopropyl methylphosphonic acid (IMPA) and ethyl methylphosphonic acid (EMPA) also were excreted in large amounts with taking the simlllllllllllllar excretion pattern of IPA and EtOH. (3) The metabolite only derived from sarin and ethylsarin is F anions whose integral output in the urine was less than the equimolar level of the excreted (IMPA+EMPA+IPA+EtOH). (4) Other corroborative findings were low lethality : of more than 5,510 patients treated, 11 were acutely dead. (5) Nine exposed males had higher sister chromatid exchange (SCE) rate (5.00±1.48/cell) than the control (3.81±0.697/cell), because dialkyl methylphosphonates seemed to have alkylating activity and producing DNA adducts. The SCE rate also increased after the in vitro exposure of lymphocytes to dialkyl methylphosphonates.

DOI： 10.2131/jts.23.SupplementII_250

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

N,N-Diethylaniline is a reagent used in organic synthesis and is an important intermediate in the manufacturing of dyes. To evaluate its genotoxicity, we examined whether it can induce sister chromatid exchanges (SCEs) in human lymphocytes. We found that N,N-diethylaniline significantly increased the frequency of SCEs both in the absence and presence of S-9 mix. The SCEs from cultures treated by N,N-diethylaniline in the presence of S-9 mix displayed a marked increase which was about 5-fold greater than the control. ANOVA analyses indicated that there is a dose-response relationship between doses of N,N-diethylaniline and the frequency of SCEs, especially in the presence of S-9 mix. The results suggested that N,N-diethylaniline has genotoxicity. (C) 1997 Elsevier Science B.V.

DOI： 10.1016/S1383-5718(97)00162-9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER VERLAG  

We evaluated cross-sensitization between p-phenylenediamine (pPDA) and p-aminophenol (pAP) or m-phenylenediamine (mPDA) by a modified lymphocyte transformation test. Guinea pigs were sensitized with pPDA using the maximization test procedure. Lymph node cells from the animals were then cultured with pPDA, pAP or mPDA in the presence or absence of epidermal cells (EC). Transformed lymphocyte counts were evaluated by means of H-3-thymidine uptake. Non-sensitized guinea pigs were used as controls. Blastogenesis in lymphocytes from sensitized guinea pigs was enhanced when cultured with pPDA, pAP or mPDA in the absence or presence of EC than without the sensitizers, and the extent of response depended on the concentration of pPDA, pAP or mPDA added to the cultures. Blastogenesis in lymphocytes from control animals was not significantly enhanced in response to pPDA, pAP or mPDA in the presence or absence of EC. The extent of the response to pPDA was greater than that to pAP, which in turn was greater than that to mPDA. In contrast, because pPDA, pAP and mPDA are color developing agents, cross-sensitization between pPDA and pAP or mPDA could not be evaluated by the results of an in vivo challenge due to pigmentation in the patch application sites. The results suggested that there is cross-sensitization between pPDA and pAP or mPDA, and that the modified lymphocyte transformation test is a useful predictive means of detecting cross-sensitization among chemicals, especially for color developing agents.

DOI： 10.1007/s002040050293

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER VERLAG  

We evaluated cross-sensitization between p-phenylenediamine (pPDA) and p-aminophenol (pAP) or m-phenylenediamine (mPDA) by a modified lymphocyte transformation test. Guinea pigs were sensitized with pPDA using the maximization test procedure. Lymph node cells from the animals were then cultured with pPDA, pAP or mPDA in the presence or absence of epidermal cells (EC). Transformed lymphocyte counts were evaluated by means of H-3-thymidine uptake. Non-sensitized guinea pigs were used as controls. Blastogenesis in lymphocytes from sensitized guinea pigs was enhanced when cultured with pPDA, pAP or mPDA in the absence or presence of EC than without the sensitizers, and the extent of response depended on the concentration of pPDA, pAP or mPDA added to the cultures. Blastogenesis in lymphocytes from control animals was not significantly enhanced in response to pPDA, pAP or mPDA in the presence or absence of EC. The extent of the response to pPDA was greater than that to pAP, which in turn was greater than that to mPDA. In contrast, because pPDA, pAP and mPDA are color developing agents, cross-sensitization between pPDA and pAP or mPDA could not be evaluated by the results of an in vivo challenge due to pigmentation in the patch application sites. The results suggested that there is cross-sensitization between pPDA and pAP or mPDA, and that the modified lymphocyte transformation test is a useful predictive means of detecting cross-sensitization among chemicals, especially for color developing agents.

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Other Link： http://search.jamas.or.jp/link/ui/1997068083

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI IRELAND LTD  

To examine the validity of a modified lymphocyte transformation test for evaluating contact hypersensitivity from weak sensitizers, guinea pigs were sensitized with formaldehyde (F) or tetramethylthiuram monosulfide (TMTM) using the maximization test procedure. Lymph node cells from the animals were then cultured with F or TMTM, in the presence or absence of epidermal cells (EC). Transformed lymphocyte counts were evaluated by uptake of H-3-thymidine. Nonsensitized guinea pigs were used as controls. The lymphocytes from sensitized guinea pigs showed stronger blastogenesis when cultured with F or TMTM in the presence of EC than when the sensitizers were not added to the culture and the response depended on the concentration of F or TMTM. Cultures in the absence of EC also showed significant enhancement of blastogenesis by F or TMTM, but the responses were significantly weaker than those in the presence of EC. Lymphocytes from the control animals did not show significantly enhanced blastogenesis in response to F or TMTM, even when EC was added to the cultures. The results suggested that contact sensitivity for weak sensitizers can be evaluated by this modified lymphocyte transformation test, especially when lymph node cells were co-cultured with EC.

DOI： 10.1016/0300-483X(95)03117-X

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI IRELAND LTD  

To examine the validity of a modified lymphocyte transformation test for evaluating contact hypersensitivity from weak sensitizers, guinea pigs were sensitized with formaldehyde (F) or tetramethylthiuram monosulfide (TMTM) using the maximization test procedure. Lymph node cells from the animals were then cultured with F or TMTM, in the presence or absence of epidermal cells (EC). Transformed lymphocyte counts were evaluated by uptake of H-3-thymidine. Nonsensitized guinea pigs were used as controls. The lymphocytes from sensitized guinea pigs showed stronger blastogenesis when cultured with F or TMTM in the presence of EC than when the sensitizers were not added to the culture and the response depended on the concentration of F or TMTM. Cultures in the absence of EC also showed significant enhancement of blastogenesis by F or TMTM, but the responses were significantly weaker than those in the presence of EC. Lymphocytes from the control animals did not show significantly enhanced blastogenesis in response to F or TMTM, even when EC was added to the cultures. The results suggested that contact sensitivity for weak sensitizers can be evaluated by this modified lymphocyte transformation test, especially when lymph node cells were co-cultured with EC.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS  

DOI： 10.1006/enrs.1993.1104

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DOI： 10.1539/joh1959.35.200

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MUNKSGAARD INT PUBL LTD  

Dose-response relationships in contact sensitivity were evaluated in guinea pigs using an in vitro assay. Guinea pigs were sensitized with different doses of 1-chloro-2,4-dinitrobenzene (DNCB) and challenged with DNCB and 2,4-dinitrobenzene sulfonic salt (DNBS). Lymph node cells from sensitized and control guinea pigs were cultured in the presence of different doses of DNCB and DNBS at 8 x 10(5) cells/well, respectively. The sensitivity was evaluated by the lymphocyte transformation test (LTT), which was assessed by uptake of H-3-thymidine. The results indicated that there were significant correlations between the doses of sensitizers and the values of LTT in both phases of induction and challenge. Thus. the presence of higher numbers of LTT-reactive lymphocytes in the circulation may well correlate with the sensitizing doses. The values examined by in vitro assay correlated well with patch test readings (r = 0.653), indicating that following the increment of degree of patch test reactions, the values of SI were also increased. The in vitro LTT may discriminate between positive patch test reactions and negative or doubtful reactions, but not between weak positive and strong positive reactions. The in vitro assay reproduced the cross-reaction between DNCB and DNBS which was confirmed in vivo.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MUNKSGAARD INT PUBL LTD  

A 42-year-old female shiitake grower was investigated to clarify the etiology of skin lesions which developed during the planting of shiitake hyphae into bed logs. She complained of repeated eczematous skin lesions during the planting season, from March to July, for 10 years. She handled 7,000 pieces of small conic blocks made of beech, with shiitake hyphae attached to their surface, per day, and 300,000 pieces altogether per season. She was positive on patch testing with extracts of shiitake hyphae. In contrast, female shiitake growers with skin lesions associated with work other than planting, and without skin lesions, were negative on patch testing to the hyphae. Moderate allergenicity was observed to extracts of shiitake hyphae in a guinea pig maximization test. These findings indicated the etiology of skin lesions in shiitake growers to be allergic contact dermatitis induced by shiitake hyphae.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MUNKSGAARD INT PUBL LTD  

Skin blood flow in allergic contact reactions and cross-sensitivity were evaluated using laser Doppler flowmetry (LDF) to study the dose-response relationships in phases of induction and challenge in guinea pigs. Guinea pigs were sensitized with different doses of 1-chloro-2,4-dinitrobenzene (DNCB) and challenged with different doses of DNCB and 2,4-dinitrobenzene sulfonic sodium salt (DNBS). The skin reactions were evaluated by LDF and visual reading score. The results indicated that there were dose-response relationships between the doses of DNCB and LDF measurements in both phases of induction and challenge, that there was a cross-reaction between DNCB and DNBS, and that the reactions at 24 h were greater than that at 48 h after removal of the patches. LDF may discriminate between positive patch test reactions and negative or doubtful reactions, but not between weak positive and strong positive reactions. This is because vascular dilatation and increase of flow already reaches a maximum in weak reactions. The more advanced phases are dominated by oedema formation. This is simply the nature of the inflammatory reaction, rather than a methodological error. The important point is that LDF can separate positive reactions from negative/uncertain reactions. The results indicated that LDF, as a non-invasive technique, may objectively and quantitatively evaluate the dose-response relationships of contact sensitivity of sensitizers.

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Language：English   Publishing type：Research paper (scientific journal)  

To assess the contact allergic potential of sensitizers, an in vitro predictive model was developed. First of all, guinea pigs were sensitized by l-chloro-2-4-dinitrobenzene (DNCB), and lymph node cells from sensitized and control guinea pigs were cultured in the presence of DNCB, 2,4-dinitrobenzene sulfonic acid sodium salt (DNBS), DNCB plus epidermal cell (DNCB+EC), DNBS+EC and epidermal cell modified hapten (dinitrophenyl-EC, DNP-EC) at 3 × 105, 5 × 105 and 8 × 105 cells/well, respectively. Lymphocyte blastogenesis responses were assessed by uptake of 3H-thymidine. The results indicated that lymphocytes from sensitized guinea pigs responded to the foregoing antigens in vitro to a greater degree than those from control guinea pigs and the blastogenesis response by DNBS was the highest among the challenges of DNBS, DNCB, DNCB+EC, DNBS+EC and DNPEC. When the number of lymphocytes was sufficient, the blastogenesis response of lymphocytes could be in vitro challenged successfully not only by DNBS, DNCB+EC, DNBS+EC and DNP-EC, but also DNCB alone. There was a cross sensitivity between DNCB and DNBS for in vivo and in vitro challenges. Moreover, significant relationships were observed between lymphocyte blastogenesis response and doses of DNBS used in vitro assay at 5 × 105 and 8 × 105 cells/well. The results indicate that this assay is an useful in vitro predictive model of contact sensitivity and cross sensitivity of sensitizers. © 1991, Japan Society for Occupational Health. All rights reserved.

DOI： 10.1539/joh1959.33.509

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

Ten patients with human T lymphotropic virus type I-associated myelopathy (HAM), 5 asymptomatic HTLV-I carriers and 11 healthy normal volunteers were studied to determine if peripheral blood lymphocytes spontaneously release IL-2 and soluble IL-2 receptors. Peripheral blood lymphocytes obtained from HAM patients proliferated spontaneously when cultured for 5 days in vitro. Proliferating cells were CD3+ lymphocytes and both CD4+ cells and CD8+ cells as shown by morphologic and immunohistochemical observations. These T cell responses were also found in asymptomatic carriers, but the responses were not as marked as those of HAM patients. IL-2 activity in the culture supernatants was much higher in HAM patients than in asymptomatic carriers; IL-2 activity correlated well with the intensity of spontaneous proliferation of lymphocytes. Furthermore, soluble IL-2 receptors in the cell-free supernatants from HAM patients were markedly increased compared to those from asymptomatic carriers. These results indicate that spontaneous proliferation of T cells is intimately related to HTLV-I infection and is probably due to autocrine or paracrine pathways which involve IL-2 and IL-2 receptor system.

DOI： 10.2169/internalmedicine1962.29.487

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

Ten patients with human T lymphotropic virus type I-associated myelopathy (HAM), 5 asymptomatic HTLV-I carriers and 11 healthy normal volunteers were studied to determine if peripheral blood lymphocytes spontaneously release IL-2 and soluble IL-2 receptors. Peripheral blood lymphocytes obtained from HAM patients proliferated spontaneously when cultured for 5 days in vitro. Proliferating cells were CD3+ lymphocytes and both CD4+ cells and CD8+ cells as shown by morphologic and immunohistochemical observations. These T cell responses were also found in asymptomatic carriers, but the responses were not as marked as those of HAM patients. IL-2 activity in the culture supernatants was much higher in HAM patients than in asymptomatic carriers; IL-2 activity correlated well with the intensity of spontaneous proliferation of lymphocytes. Furthermore, soluble IL-2 receptors in the cell-free supernatants from HAM patients were markedly increased compared to those from asymptomatic carriers. These results indicate that spontaneous proliferation of T cells is intimately related to HTLV-I infection and is probably due to autocrine or paracrine pathways which involve IL-2 and IL-2 receptor system.

DOI： 10.2169/internalmedicine1962.29.487

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DOI： 10.2185/jjrm.39.64

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DOI： 10.1539/joh1959.31.301

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Language：English   Publisher：THE JAPANESE ASSOCIATION OF RURAL MEDICINE  

The outbreak of skin hazards from okra cultivation was studied by a field survey. About a half (46.2 %) of 186 workers investigated (male, 76 ; female, 110) reported to have experienced pastly or annually skin hazards from okra cultivation.The sites of lesion complained were mostly the arms (47.5%), neck (41.3%), fingers (32.5%) and so forth in total number. The degree of lesions were generally itching (85.0%) and flare (61.3%), but severe cases like vanishing fingerprints (16.3%) and fissures on the fingers (11.3 %) were also revealed. Portion of okra responsible for skin hazards seemed to be mainly leaves, trichomes and pods.<BR>Positive patch test reactions with preparations of immature okra pods in 46 workers (male, 12 ; female, 34), compared to 112 control subjects (male, 84 ; female, 28), were significantly higher in okra workers than in controls, which were 25% in males and 20% in total group.<BR>These results show that okra components cause irritant contact dermatitis and allergic contact dermatitis as well.

DOI： 10.2185/jjrm.38.24

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To investigate the effects of forest environments on cardiovascular and metabolic parameters, sixteen healthy male subjects (mean age: 57.4±11.6 years) were selected after obtaining informed consent. The subjects took day trips to a forest park in the suburbs of Tokyo and to an urban area of Tokyo as a control in September 2010. On both trips, they walked for two hours in the morning and afternoon on a Sunday. Blood and urine were sampled on the morning before each trip and after each trip. Blood pressure was measured on the morning (0800) before each trip, at noon (1300), in the afternoon (1600) during each trip, and on the morning (0800) after each trip. The day trip to the forest park significantly reduced blood pressure and urinary noradrenaline and dopamine levels and significantly increased serum adiponectin and dehydroepiandrosterone sulfate (DHEA-S) levels. Walking exercise also reduced the levels of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), blood HbA1c and urinary dopamine. However, forest environments did not affect the levels of triglycerides, total Cho, LDL-Cho, HDL-Cho, RLP-Cho, insulin, or hs-CRP in serum, blood glucose, or hematological parameters. Taken together, habitual walking in forest environments may lower blood pressure by reducing sympathetic nerve activity and have beneficial effects on blood adiponectin and DHEA-S levels, and habitual walking exercise may have beneficial effects on blood NT-proBNP levels.© 2013 by Nova Science Publishers, Inc. All rights reserved.

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.toxlet.2012.03.482

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Language：Japanese   Publisher：(一社)日本衛生学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.toxlet.2011.05.527

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本衛生学会  

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Language：Japanese   Publisher：(一社)日本衛生学会  

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Language：Japanese   Publisher：日本成人病(生活習慣病)学会  

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J-GLOBAL

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.toxlet.2010.03.653

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Language：Japanese   Publisher：(公社)日本産業衛生学会  

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Language：Japanese   Publisher：(一社)日本衛生学会  

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Language：Japanese   Publisher：(一社)日本衛生学会  

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Language：Japanese   Publisher：(公社)日本生化学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.toxlet.2009.06.677

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Language：Japanese  

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2009259729

Language：English   Publisher：博慈会老人病研究所  

CiNii Books

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Language：Japanese   Publisher：(公社)日本薬学会  

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Language：Japanese   Publisher：(一社)日本衛生学会  

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Language：Japanese   Publisher：(公社)日本産業衛生学会  

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Language：Japanese  

CiNii Books

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CiNii Books

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Language：Japanese   Publisher：(公社)日本産業衛生学会  

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Language：Japanese   Publisher：(公社)日本薬学会  

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Language：Japanese   Publisher：(一社)日本衛生学会  

CiNii Books

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

DOI： 10.1016/j.clim.2008.03.028

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Language：Japanese   Publisher：(公社)日本産業衛生学会  

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Language：Japanese  

CiNii Books

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CiNii Books

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CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2007151870

Language：Japanese   Publisher：(一社)日本衛生学会  

CiNii Books

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：BLACKWELL PUBLISHING  

Web of Science

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Language：Japanese   Publisher：(公社)日本産業衛生学会  

DOI： 10.1539/sangyoeisei.KJ00004429580

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Language：English   Publisher：TAYLOR & FRANCIS LTD  

DOI： 10.1080/10253890512331391536

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Language：Japanese   Publisher：(公社)日本薬学会  

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Language：Japanese  

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Language：Japanese   Publisher：(公社)日本薬学会  

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Language：Japanese   Publisher：(公社)日本産業衛生学会  

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Language：Japanese   Publisher：(公社)日本薬学会  

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Language：Japanese  

CiNii Books

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Language：Japanese   Publisher：(公社)日本生化学会  

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Language：Japanese   Publisher：(公社)日本生化学会  

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Language：Japanese   Publisher：(公社)日本産業衛生学会  

CiNii Books

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Language：Japanese   Publisher：(公社)日本産業衛生学会  

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Language：Japanese   Publisher：(公社)日本産業衛生学会  

CiNii Books

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Language：English   Publisher：ELSEVIER SCI IRELAND LTD  

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Language：Japanese   Publisher：(公社)日本産業衛生学会  

DOI： 10.1539/sangyoeisei.KJ00001991076

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Language：English   Publisher：MUNKSGAARD INT PUBL LTD  

Skin blood flow in allergic contact reactions and cross-sensitivity were evaluated using laser Doppler flowmetry (LDF) to study the dose-response relationships in phases of induction and challenge in guinea pigs. Guinea pigs were sensitized with different doses of 1-chloro-2,4-dinitrobenzene (DNCB) and challenged with different doses of DNCB and 2,4-dinitrobenzene sulfonic sodium salt (DNBS). The skin reactions were evaluated by LDF and visual reading score. The results indicated that there were dose-response relationships between the doses of DNCB and LDF measurements in both phases of induction and challenge, that there was a cross-reaction between DNCB and DNBS, and that the reactions at 24 h were greater than that at 48 h after removal of the patches. LDF may discriminate between positive patch test reactions and negative or doubtful reactions, but not between weak positive and strong positive reactions. This is because vascular dilatation and increase of flow already reaches a maximum in weak reactions. The more advanced phases are dominated by oedema formation. This is simply the nature of the inflammatory reaction, rather than a methodological error. The important point is that LDF can separate positive reactions from negative/uncertain reactions. The results indicated that LDF, as a non-invasive technique, may objectively and quantitatively evaluate the dose-response relationships of contact sensitivity of sensitizers.

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Language：Japanese   Publisher：Japan Society for Occupational Health  

CiNii Books

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Language：Japanese   Publisher：Japan Society for Occupational Health  

CiNii Books

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Language：Japanese   Publisher：Japan Society for Occupational Health  

CiNii Books

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Language：Japanese   Publisher：Japan Society for Occupational Health  

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Language：Japanese   Publisher：Japan Society for Occupational Health  

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Language：Japanese   Publisher：Japan Society for Occupational Health  

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Language：Japanese   Publisher：公益社団法人日本産業衛生学会  

CiNii Books

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Language：Japanese   Publisher：Japan Society for Occupational Health  

CiNii Books

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Language：Japanese   Publisher：Japan Society for Occupational Health  

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Language：Japanese   Publisher：Japan Society for Occupational Health  

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Language：Japanese   Publisher：公益社団法人日本産業衛生学会  

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Event date： 2022.7

Language：English   Presentation type：Oral presentation (keynote)  

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Event date： 2022.6

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2022.5

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Event date： 2022.3

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Event date： 2022.3

Language：Japanese   Presentation type：Oral presentation (invited, special)  

File： 日本衛生学会賞受賞講演抄録.pdf

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Event date： 2022.3

Language：English   Presentation type：Symposium, workshop panel (public)  

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Event date： 2022.3

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Event date： 2022.3

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Event date： 2021.10

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Event date： 2021.5

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Event date： 2021.5

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Event date： 2021.4 - 2021.5

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Event date： 2021.3

Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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Event date： 2021.3

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Event date： 2021.3

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Event date： 2021.3

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Event date： 2020.8

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Event date： 2020.3

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Event date： 2020.3

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Event date： 2020.3

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Event date： 2019.11

Language：English   Presentation type：Oral presentation (invited, special)  

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Event date： 2019.11

Language：English   Presentation type：Oral presentation (keynote)  

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Event date： 2019.10

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Event date： 2019.6

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2019.6

Language：English   Presentation type：Poster presentation  

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Event date： 2019.5

Language：English   Presentation type：Symposium, workshop panel (nominated)  

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