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Kazuhito Yokoyama

Publications and source records attributed to Kazuhito Yokoyama.

At least 19 recordsLinked to original sources
PubMed2007

Genotoxic effects of alcohol in human peripheral lymphocytes modulated by ADH1B and ALDH2 gene polymorphisms.

Ethanol is almost totally broken down by oxidative metabolism in vivo. Ethanol per se is considered to be neither carcinogenic, mutagenic nor genotoxic. However, during the metabolic conversion of ethanol to acetaldehyde and acetate, the organism is exposed to both ethanol and acetaldehyde and therefore ethanol is suspected to be co-carcinogenic. The genetic polymorphisms of alcohol dehydrogenase-2 (ADH1B) and acetaldehyde dehydrogenase-2 (ALDH2) influence the metabolism of alcohol. The ADH1B*1/*1 genotype encodes the low-activity form of ADH1B, and ALDH2*1/*2 and ALDH2*2/*2 genotype encode inactive ALDH2. The aim of this study was to test the hypothesis that polymorphisms of the ADH1B and ALDH2 genes are significantly associated with genotoxicity induced by alcohol drinking, measured using the cytokinesis-block micronucleus (CBMN) assay, an established biomarker of genome instability, in peripheral blood lymphocytes of 286 healthy Japanese men. There was a significant trend for the mean micronuclei (MN) frequency in habitual or moderate drinkers without a smoking habit to increase as the numbers of the *1 allele in ADH1B increased (P=0.039 or P=0.029) and the *2 allele in ALDH2 increased (P=0.019 or P=0.037). A logistic regression analysis showed that the number of subjects with MN frequency levels more than median value of MN (3.0) was significantly higher in the subjects with the ADH1B*1 allele as adjusted estimates (OR 2.08, 95% C.I. 1.24-3.48), when the OR for the subjects with the ADH1B*2/*2 genotype was defined as 1.00. The number of subjects with MN frequency levels more than median value of MN was also significantly higher in the subjects with the ALDH2*2 allele as adjusted estimates (OR 1.79, 95% C.I. 1.04-3.11), when the OR for the subjects with the ALDH2*1/*1 genotype was defined as 1.00. The results of this study have identified important novel associations between ADH1B/ALDH2 polymorphisms and genotoxicity in alcohol drinkers.

Adult↗
PubMed2006

Our recent experiences with sarin poisoning cases in Japan and pesticide users with references to some selected chemicals.

Attention has been paid to neurobehavioral effects of occupational and environmental exposures to chemicals such as pesticides, heavy metals and organic solvents. The area of research that includes neurobehavioral methods and effects in occupational and environmental health has been called "Occupational and Environmental Neurology and Behavioral Medicine." The methods, by which early changes in neurological, cognitive and behavioral function can be assessed, include neurobehavioral test battery, neurophysiological methods, questionnaires and structured interview, biochemical markers and imaging techniques. The author presents his observations of neurobehavioral and neurophysiological effects in Tokyo subway sarin poisoning cases as well as in pesticide users (tobacco farmers) in Malaysia in relation to Green Tobacco Sickness (GTS). In sarin cases, a variety effects were observed 6-8 months after exposure, suggesting delayed neurological effects. Studies on pesticide users revealed that organophosphorus and dithiocarbamate affected peripheral nerve conduction and postural balance; subjective symptoms related to GTS were also observed, indicating the effects of nicotine absorbed from wet tobacco leaves. In addition, non-neurological effects of pesticides and other chemicals are presented, in relation to genetic polymorphism and oxidative stress.

Agricultural Workers' Diseases↗
PubMed2006

A polymorphism of the methionine synthase reductase gene increases chromosomal damage in peripheral lymphocytes in smokers.

The cytogenetic effects of cigarette smoke has been evaluated as one of many potential confounders in a large number of biomonitoring studies of occupationally or environmentally exposed populations and control subjects. Despite the well-known presence of carcinogens in the cigarette smoke, the results in the scientific literature linking smoking habits to micronuclei (MN) frequency, one of the cytogenetic markers, are rather controversial. Here, we investigated the relationships among MN frequency, smoking habits and five folate metabolic enzyme gene polymorphisms (MTHFR C677T and A1298C, MTR A2756G, MTRR A66G and TYMS 3'UTR) in 132 healthy Japanese men who were non-habitual drinkers. In never- and former-smokers, no statistically significant differences in the mean MN frequencies were observed according to the five folate metabolic enzyme gene polymorphisms. In current-smokers, however, subjects with the AA genotype for MTRR had a significantly higher mean MN frequency than the AG genotypes for MTRR (p<0.05). Furthermore, among subjects with the AA genotype for MTRR, current-smokers were found to have a significantly higher mean MN frequency than never- and former-smokers (p<0.05). To further characterize this association, we stratified the smoking status into five groups: non-smokers (never-smokers and former-smokers), 1-10 cigarettes/day, 11-20 cigarettes/day, 21-30 cigarettes/day and >or=31 cigarettes/day. There was an overall trend for the mean MN frequency in subjects with the MTRR AA genotype to increase as the number of cigarettes smoked per day increased (p<0.01, Jonckheere-Terpstra test). The results of our preliminary study suggest that the MTRR AA genotype acts to increase the MN frequency resulting from cigarette smoking. Therefore, studies on human genotoxicity based on cytogenetic markers of MN should take into account both the MTRR polymorphism and the potential confounding effect of smoking, although these preliminary findings need to be validated in larger populations because of the relatively small sample size.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2006

Decreases in CD8+ T, naive (CD4+CD45RA+) T, and B (CD19+) lymphocytes by exposure to manganese fume.

To examine the effects of exposure to manganese (Mn) on the cellular and humoral immune system in men, T lymphocyte subpopulations, B (CD19+) lymphocytes, natural killer (NK) cells, and serum immunoglobulins (i.e., IgG, IgA and IgM) together with total T (CD3+) lymphocytes and total lymphocytes were measured in blood samples from 21 welders mainly exposed to Mn fume with blood Mn (BMn) concentrations of 0.6-2.3 (mean 1.4) microg/dl and 21 healthy controls working in the same factory (BMn concentrations: 0.7 to 1.7, mean 1.1 microg/dl). The workers engaged in welding for 6 to 36 (mean 17) yr. All the study subjects were divided into 3 equally sized groups (n=14 for each group) according to BMn concentrations. Numbers of CD8+ T, total T (CD3+), B (CD19+), and total lymphocytes were significantly lower in high-BMn group than those in low-BMn group; the numbers of CD8+ T lymphocytes were significantly lower in moderate-BMn group compared to low-BMn group. After adjusting for age and smoking, significant inverse correlations between BMn concentrations and CD4+CD45RA+ T, CD4+ T, CD8+ T, CD3+ T, and total lymphocytes were found. We conclude that T lymphocytes, especially CD8+ and CD4+CD45RA+ T lymphocytes, as well as CD19+ B lymphocytes are affected by exposure to Mn fume.

Adult↗
PubMed2005

Genotoxic damage in female residents exposed to environmental air pollution in Shenyang city, China.

Air pollution has been suggested to cause genetic damage from investigations of many biological markers that measure cytogenetic damage in humans. Here, we evaluated the genotoxic effects of ambient air pollution by investigating the extent of cytogenetic damage in human blood lymphocytes from rural and industrial female residents of Shenyang city, China, using micronuclei assays and polymorphic analyses of metabolic enzyme and DNA repair genes. After adjustment for potential confounding factors including DNA polymorphisms, industrial female residents were found to have a higher micronuclei frequency. These results provide evidence that micronuclei assays are a sensitive indicator to air pollution-induced genotoxic effects in humans.

Adult↗
PubMed2005

Relationship between fetal weight, placental growth and litter size in mice from mid- to late-gestation.

In mammals, the placenta, which consists of maternal and fetal components, is important in fetal development because it supplies the fetus with the nourishment it needs. We investigated the effects of placental growth and litter size on mouse fetal weights from mid- to late-gestation. The mean weight of male fetuses at 13.5 days post coitum (dpc) was larger than that of females. Although there was a significant correlation between fetal and placental weights in both males and females during mid-gestation (P<0.05), there was no correlation during late-gestation. However, a significant correlation was observed between litter size and fetal weights in both males and females at 17.5 dpc (P<0.05). These findings suggest that fetal weight is regulated by placental growth during mid-gestation, while the effects of litter size are more prominent towards late-gestation.

Animals↗
PubMed2005

Gene-environmental interactions between alcohol-drinking behavior and ALDH2 and CYP2E1 polymorphisms and their impact on micronuclei frequency in human lymphocytes.

Ethanol is converted to acetaldehyde by alcohol dehydrogenase (ADH), cytochrome p4502E1 (CYP2E1) and catalase. This metabolite is then detoxified by aldehyde dehydrogenase 2 (ALDH2), a key enzyme in the elimination of acetaldehyde, via further oxidation to acetic acid. The toxic effects of acetaldehyde are well documented and may be partially mediated by genotoxic damage. In the present study, we investigated the effects of alcohol-drinking behavior and genetic polymorphisms in two different genes (ALDH2 and CYP2E1) on the micronuclei (MN) frequency in 248 healthy Japanese men. Genotyping was performed by PCR-RFLP analysis. The ALDH2 variant (deficient type) was significantly associated with an increased MN frequency in subjects drinking more than three times/wk, while habitual drinkers with wild-type CYP2E1 also had a significantly increased MN frequency. Furthermore, when the subjects were divided into eight groups according to their drinking frequency and genotypes of ALDH2 and CYP2E1, we found that habitual drinkers with homozygous CYP2E1*1/*1 and heterozygous ALDH2*1/*2 or homozygous ALDH2*2/*2 showed the highest mean MN frequency. In the present study, we found clear associations among ALDH2 and CYP2E1 gene polymorphisms, alcohol-drinking behavior and genotoxic effects in a healthy Japanese population. Therefore, analysis of the polymorphisms of alcohol-metabolizing enzymes may lead to elucidation of the mechanism(s) for individual susceptibilities to the toxicity of ethanol metabolites.

Adult↗
PubMed2005

Lead and other trace metals in preeclampsia: a case-control study in Tehran, Iran.

To assess the effects of environmental exposures to trace metals on the incidence of preeclampsia, concentrations of lead (Pb), antimony (Sb), manganese (Mn), mercury, cadmium, cobalt and zinc in umbilical cord blood (UCB) and mother whole blood (MWB) were measured in 396 postpartum women without occupational exposure to metals in Tehran, Iran, using inductively coupled plasma mass spectrometry. Mother's ages ranged from 15 to 49 (mean 27) years. Preeclampsia was diagnosed in 31 subjects (7.8%). Levels of Pb, Sb and Mn in UCB were significantly higher in preeclampsia cases [mean+/-SD of 4.30+/-2.49 microg/dl, 4.16+/-2.73 and 46.87+/-15.03 microg/l, respectively] than in controls [3.52+/-2.09 microg/dl, 3.17+/-2.68 and 40.32+/-15.19 microg/l, respectively] (P<0.05). The logistic regression analysis revealed that one unit increase in the common logarithms of UCB concentration of Pb, Sb or Mn led to increase in the risk of preeclampsia several-fold; unit risks (95% CI) were 12.96 (1.57-107.03), 6.11 (1.11-33.53) and 34.2 (1.81-648.04) for Pb, Sb and Mn, respectively (P<0.05). These findings suggest that environmental exposure to Pb, Sb and Mn may increase the risk of preeclampsia in women without occupational exposure; levels of metals in UCB to be sensitive indicators of female reproductive toxicity as compared with those in mother MWB. Further studies are necessary to confirm these findings, especially on Sb and Mn.

Adolescent↗
PubMed2005

Oxidative DNA damage in relation to neurotoxicity in the brain of mice exposed to arsenic at environmentally relevant levels.

To clarify the association between oxidative DNA damage and the neurotoxicity of arsenic, the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as an index of oxidative DNA damage in the brain was examined in mice fed with drinking water containing 1 or 2 ppm arsenic, using an HPLC-electrochemical detector and immunohistochemical method. 8-OHdG levels were significantly increased in the brain of mice given arsenic and its immunoreactivity was distributed in the cerebral and cerebellar cortexes. Cerebral cortex neurons and Purkinje cells in the cerebellar cortex showed degenerative changes in accordance with the distribution of 8-OHdG immunoreactivity. The levels of arsenic in this study were lower than those reported in epidemiological studies. Thus, we conclude that environmentally relevant levels of arsenic induce pathological changes through oxidative DNA damage in the brain tissues in vivo and that cerebral and cerebellar cortex neurons seem to be the major targets of arsenic neurotoxicity.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2005

[Use of complementary and alternative medicines among factory workers: investigation of workers in manufacturing].

To elucidate the situation of complementary and alternative medicines (CAM) in an occupational health setting, workers in a factory of a housing construction business were surveyed using self-administered questionnaires on their utilization of CAM in the past 12 months, out-of-pocket expenditures on CAM and ordinary western medicines (OWM), and reasons for the use of CAM. A total of 263 workers (84.3%) completed the questionnaires. Among them, 134 (51%) had received CAM therapy in the last 12 months: i.e. nutritional and tonic drinks (35.4%), supplements (16.3%), massage (13.7%), chiropractic or osteopathy (8.7%), health-related appliances (6.5%), herb or kampo (3.4%), aromatherapy (1.9%), acupuncture (1.9%), or other therapy (1.5%). Reasons for the use of CAM was "the condition was not serious enough to warrant OWM" and "expectation of health promotion or disease prevention" for 70 (51.9%) and 53 (39.3%) subjects, respectively. Average annual out-of-pocket expenditures for CAM and OWM were 17,500 and 21,300 yen, respectively. It seems important to further widen awareness and knowledge of CAM in occupational health.

Adult↗
PubMed2005

Music can enhance exercise-induced sympathetic dominancy assessed by heart rate variability.

Many studies have been conducted on physiological responses of music, yielding controversial results. In the present study, we examined whether music affects the exercise-induced changes in the autonomic nervous system activity in twelve healthy female college students. On the first day, the subjects were asked to rest, exercise, and then rest for 15 min, respectively. On the second day, they were asked to rest with music, exercise, and then rest with music for 15 min, respectively. Heart rate variability was measured for the pre- and post-exercise periods. Music was given according to subjects' preferences using a vibroacoustic apparatus (body sonic system), i.e. a chair on which subjects laid and felt low-pitch sounds by their body in addition to listening music. With music, ratio of low frequency to high frequency component of heart rate variability (LH/HF) was significantly increased after exercise as compared with before exercise (p < 0.01). By contrast, the changes in LH/HF were not significant without music (p > 0.05). It is suggested that after exercise in which sympathetic nerve activity is dominant, preferred music synchronizes with the activated physical response, further promoting the response and increasing sympathetic nerve activity. Combining music with exercise is therefore not only enjoyable in terms of mood but also may promote physiological excitation and enhance physical activation.

Adult↗
PubMed2005

Effects of pesticides on the peripheral and central nervous system in tobacco farmers in Malaysia: studies on peripheral nerve conduction, brain-evoked potentials and computerized posturography.

We examined the effects of pesticides on the central and peripheral nervous system in the setting of a tobacco farm at a developing country. Maximal motor and sensory nerve conduction velocities (MCV and SCV, respectively) in the median, sural and tibial nerves, postural sway, and brain-evoked potentials (auditory event-related and visual-evoked potentials) were measured in 80 male tobacco farmers and age- and sex-matched 40 controls in Kelantan, Malaysia. Median SCV (finger-wrist) in farmers using Delsen (mancozeb, dithiocarbamate fungicide), who showed significant decrease of serum cholinesterase activities, were significantly lower compared with the controls. Sural SCV in farmers using Fastac (alpha-cypermethrin, pyrethroid insecticide) and median MCV (elbow-wrist) in farmers using Tamex (butralin, dinitroaniline herbicide) were significantly slowed compared with their respective controls. In Delsen (mancozeb, dithiocarbamate) users, the power of postural sway of 0-1 Hz was significantly larger than that in the controls both in the anterior-posterior direction with eyes open and in the right-left direction with eyes closed. The former type of sway was also significantly increased in Tamaron (methamidophos, organophosphorus insecticide) users. In conclusion, nerve conduction velocities and postural sway seem to be sensitive indicators of the effects of pesticides on the central and peripheral nervous system.

Adult↗
PubMed2004

Evidence of association of the CYP2E1 genetic polymorphism with micronuclei frequency in human peripheral blood.

Micronuclei (MN) are used as one of the cytogenetic biomarkers, and intra- and inter-individual variations in this frequency have been reported in human blood lymphocytes. Polymorphisms in a few metabolic enzyme genes seem to account for a proportion of this variability, but the impacts of specific genetic variants on the MN frequency have not yet been clarified. Here, we investigated the relationship between the MN frequency and several gene polymorphisms in 90 healthy Japanese men. The subjects with the CYP2E1(*)3 variant allele had a statistically lower mean MN frequency than subjects with the CYP2E1(*)1/(*)1 wild type. Furthermore, the adjusted odds ratio (OR) of the CYP2E1(*)3 variant with higher MN frequency levels was also significantly lower and calculated to be 0.25 (95% CI 0.07-0.83), when the OR for the subjects with the CYP2E1(*)1/(*)1 wild type was defined as 1.00. These data suggest that the CYP2E1(*)3 polymorphism may have the potential to influence the baseline frequency of MN.

Adult↗
PubMed2004

Effects of urbanization, economic development, and migration of workers on suicide mortality in Japan.

The relationships between male or female age-adjusted suicide mortality and social life factors for all 47 Japanese prefectures in 1980, 1985 and 1990 were investigated by stepwise multiple regression analysis after classification of 20 social life indicators by factor analysis. During this period, Japan experienced the second economic crisis (the so-called secondary oil crisis) in 1980-1983 and economic prosperity (bubble economy) in 1986-1990. In all the three years, male suicide mortality was significantly related inversely to the urbanization and economic development factor, the result of which was consistent with the data in our previous study for the years 1970 and 1975. Similarly, the male mortality was positively related to the factor of migration of workers in the three years. No factor significantly related to female mortality for all the three years was found. It is suggested that (1) urbanization was a major determinant which prevented male suicide mortality during the past 20 years (1970-1990) in Japan; (2) migration of workers became an important factor for male suicide mortality during these 10 years; and (3) female suicide mortality was less vulnerable to social life factors for these 20 years than the male mortality.

Adolescent↗
PubMed2004

Effects of prednisolone and complex of vitamin B1, B2, B6 and B12 on organophosphorus compound-induced delayed neurotoxicity.

Protective effects of prednisolone as a synthetic adrenal cortical hormone and complex of vitamin B(1), B(2), B(6) and B (12) on organophosphorus compound-induced delayed neurotoxicity (OPIDN) caused by leptophos and tri-o-cresyl phosphate (TOCP) as organophosphates (OPs) were examined. Nine groups of hens (six for each) were used. Eight groups received intravenous injection of 30 mg/kg of leptophos or 40 mg/kg of TOCP (four groups in each). Among them, three groups which received leptophos were given (p.o.) predonisolone (2 mg/body), vitamin B complex (25 mg/body) or both 3 h after OPs injection and then every day for 15 d (one group for each); the same treatment was performed on three groups which received TOCP. The remaining one group served as controls. It was observed that delayed neuropathy induced by OPs could not be resisted completely by the treatment with prednisolone or vitamin B complex, but clinical signs of OPIDN and pathological changes in hens that received these two protective agents after OPs were less severe than those in hens that received only OPs. Of these groups, the improvement in clinical signs was best shown in hens that received the both two protective agents. In addition, improvement in clinical signs among the hens that did not deteriorate to paralysis was observed. In particular, those which developed mild ataxia recovered well. It is indicated that combining administration of prednisolone and vitamin B complex early before clinical signs are manifest is effective in alleviating neuropathy. It is also suggested that recovery or good prognosis will be expected, as long as progression of the clinical signs is prevented before paralysis develops in delayed neuropathy.

Animals↗
PubMed2004

Effects of static load on the weight and protein content in the leg muscles of the mouse: a simulation of prolonged standing in the workplace.

To simulate the effects of prolonged standing in the workplace on the leg muscles, we subjected mice to centrifugation for 6 wk. The absolute wet weight of leg muscles and internal organs of mice were measured after exposure to 3G by centrifugation for 6 wk and at 2 wk after removal of centrifugation. The weight of the soleus muscle (antigravity muscle) significantly increased after 6-wk exposure to centrifugation, but it decreased to its control weight 2 wk after removal of centrifugation. In contrast, the wet weights of the anterior tibial muscle, liver, and kidneys of mice centrifuged for 6 wk were significantly lower than those of the control mice; they had returned to control levels 2 wk after removal of centrifugation. It was therefore suggested that prolonged standing enlarged the leg muscles but its effect did not last for a long period of time after stopping prolonged standing. Western blot analysis of proteins extracted from the soleus muscle showed that vinculin and alpha-actinin in the centrifuged mice increased slightly, but there were no differences in the heat shock protein 70 (HSP70) and desmin levels between the centrifuged mice and control mice. No difference in HSP 70 suggested that muscle damage did not exist after 6 wk centrifugation.

Animal Experimentation↗
PubMed2004

Relationship between increased blood lead and pregnancy hypertension in women without occupational lead exposure in Tehran, Iran.

This study was conducted to assess the relationship between blood lead levels and pregnancy-induced hypertension. Participants were 110 pregnant women, of whom 55 were hypertensive, 27 +/- 5.6 yr of age (mean +/- standard deviation) (range = 17-40 yr); the other 55 women were age- and gravidity-matched normotensive controls. Participants were selected on the basis of their medical history and the results of a questionnaire-based interview. Subjects were at gestational ages 37 +/- 2.5 wk (range = 30-41 wk) and were not occupationally exposed to lead. Blood samples were collected within 24 hr after delivery, and blood lead levels were measured. For the hypertensive cases, blood lead levels were 5.7 +/- 2 microg/dl (range = 2.2-12.6 microg/dl [0.27 +/- 0.10 micromol/l; range = 0.11-0.60 micromol/l]), which were significantly higher than those of the control group (i.e., 4.8 +/- 1.9 microg/dl; range = 1.9-10.6 microg/dl [0.23 +/- 0.09 micromol/l; range = 0.09-0.51 micromol/l]). There were no significant differences in blood lead concentrations among hypertensive subjects with proteinuria (n = 30) and those without proteinuria (n = 25). Results of this study indicated that low-level lead exposure may be a risk factor for pregnancy hypertension.

Adolescent↗