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  1. Yokoyama K
    Neurotoxicology, 2007 Mar;28(2):364-73.
    PMID: 16730798
    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.
  2. Bin Nordin R, Araki S, Sato H, Yokoyama K, Bin Wan Muda WA, Win Kyi D
    Malays J Med Sci, 2001 Jan;8(1):1-10.
    PMID: 22973149 MyJurnal
    To identify gender difference in safe and unsafe practice of pesticide handling in tobacco farmers of Malaysia, we conducted a 20-item questionnaire interview on storage of pesticide (4 questions), mixing of pesticide (3 questions), use of personal protective equipment and clothing while spraying pesticide (7 questions), activities during and after spraying of pesticide (5 questions), and maintenance of pesticide sprayer (1 question) in 496 tobacco farmers (395 males and 101 females) in Bachok District, Kelantan, Malaysia. Duration of employment was significantly longer in females than those in males (p<0.001). In addition, proportion with no formal education in females was significantly higher than those in males (p<0.05). The following eight common factors were extracted from the 20 questionnaires by principal components factor analysis after varimax rotation in all farmers: (1) use of personal protective equipment, (2) unsafe work habit, (3) reading and following instructions on pesticide label, (4) security, storage and disposal of pesticide container, (5) safe work habit, (6) proper handling of pesticide and maintenance of pesticide sprayer, (7) use of personal protective clothing, and (8) safe handling of pesticide. Results of analysis of covariance for the eight factor scores of all male and female farmers, controlling for educational level and duration of employment, showed that: (1) factor scores for use of personal protective equipment (p<0.001), use of personal protective clothing (p<0.001) and safe work habit (p<0.001) in females were significantly lower than those in males; (2) conversely, factor scores for reading and following instruction on pesticide label (p<0.001) and proper handling of pesticide and maintenance of pesticide sprayer (p<0.01) in males were significantly lower than those in females; and (3) there were no significant differences in other three factor scores (p>0.05). We therefore conclude that: (1) for female tobacco farmers, choice of personal attire tend to result in lower scores on use of personal protective equipment and personal protective clothing while personal hygiene practices result in lower score on safe work habit; and, (2) for male tobacco farmers, the lower scores on reading and following instruction on pesticide label and mixing pesticide and maintenance of pesticide sprayer in good condition suggests that they were not primarily involved in these activities. It is postulated that these differences in safe and unsafe practices of pesticide handling across gender is related to the choice of personal attire, personal hygiene practices and division of labour within farming households which in turn is influenced by prevailing sociocultural norms in the community.
  3. Nordi RB, Araki S, Sato H, Yokoyama K, Wan Muda WA, Win Kyi D
    Ind Health, 2002 Apr;40(2):182-90.
    PMID: 12064560
    The effects of safety behaviours associated with pesticide use on the occurrence of acute organ symptoms in 395 male and 101 female tobacco-growing farmers in Malaysia were studied. We used a 15-questionnaire checklist on safe pesticide-use behaviours and a 25-questionnaire checklist on acute organ symptoms reported shortly after spraying pesticides. Results of stepwise multiple linear regression analysis indicated that no smoking while spraying, good sprayer-condition, and changing clothes immediately after spraying significantly prevented occurrence of acute symptoms just after pesticide spray in male farmers; in female farmers, only wearing a hat while spraying significantly prevented the symptoms. Safety behaviours in pesticide use in male and female tobacco-growing farmers are discussed in the light of these findings.
  4. Tamrin SB, Yokoyama K, Jalaludin J, Aziz NA, Jemoin N, Nordin R, et al.
    Ind Health, 2007 Apr;45(2):268-78.
    PMID: 17485871
    To determine the risk factors associated with complain of low back pain. A cross sectional study was done from June 2004 until August 2005. Seven hundred and sixty commercial vehicle drivers from 11 bus companies in central, northern and eastern regions in Malaysia participated in this study. Modified Nordic questionnaire was used to determine the prevalence of low back pain; Maestro human vibration meter was used to measure the personal R.M.S values of lateral, anterior-posterior and vertical axes. Modified Owas was used to assess the awkward posture of the driver torso namely, bending forward movement, leaning, sitting straight and twisting. Profile of Mood States (POMS) was used to evaluate the mood states of bus drivers with complain of low back pain. A high prevalence of low back pain (60.4%) among Malaysian commercial vehicle drivers was found. Logistic regression analysis controlling for age, income, education level and non occupational activities revealed that the following factors were related to low back pain: Tension-anxiety [1.080, 95% CI 1.041-1.121], depression dejection [1.047, 95% CI 1.023-1.072], anger-hostility [1.053, 95% CI 1.027-1.081], fatigue [1.132, 95% CI 1.089-1.177] and confusion [1.114, 95% CI 1.061-1.169] of POMS, length of employment [1.001, 95% CI 1.0-1.003], steering wheel adjustment [1.521, 95% CI 1.101-2.101], perception of exposing to vibration [1.943, 95% CI 1.389-2.719]. In conclusion, combinations of risks lead to high increase of low back pain complain among Malaysian bus drivers.
  5. Kimura K, Yokoyama K, Sato H, Nordin RB, Naing L, Kimura S, et al.
    Ind Health, 2005 Apr;43(2):285-94.
    PMID: 15895843
    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.
  6. Onuki M, Yokoyama K, Kimura K, Sato H, Nordin RB, Naing L, et al.
    J Occup Health, 2003 May;45(3):140-5.
    PMID: 14646288
    To assess dermal absorption of nicotine from tobacco leaves in relation to Green Tobacco Sickness (GTS), urinary cotinine concentrations were measured in 80 male tobacco-growing farmers and in 40 healthy males (controls) who did not handle wet tobacco leaves in Kelantan, Malaysia. Among non-smokers, urinary cotinine levels in farmers were significantly higher than those of controls; farmers with urinary cotinine of 50 ng/ml/m2 or above showed eye symptoms more frequently than those below this level (p<0.05). Farmers who did not wear protective equipment had subjective symptoms more frequently than those who used the equipment (p<0.05); some of these symptoms were seen more frequently in organophosphate (Tamaron) users than in non-users. As tobacco farmers evidence a risk of nicotine poisoning from tobacco leaves, assessment including GTS together with effects of pesticides will be necessary.
  7. Higuchi H, Yamakawa N, Imadome KI, Yahata T, Kotaki R, Ogata J, et al.
    Blood, 2018 06 07;131(23):2552-2567.
    PMID: 29685921 DOI: 10.1182/blood-2017-07-794529
    Epstein-Barr virus (EBV) causes various diseases in the elderly, including B-cell lymphoma such as Hodgkin's lymphoma and diffuse large B-cell lymphoma. Here, we show that EBV acts in trans on noninfected macrophages in the tumor through exosome secretion and augments the development of lymphomas. In a humanized mouse model, the different formation of lymphoproliferative disease (LPD) between 2 EBV strains (Akata and B95-8) was evident. Furthermore, injection of Akata-derived exosomes affected LPD severity, possibly through the regulation of macrophage phenotype in vivo. Exosomes collected from Akata-lymphoblastoid cell lines reportedly contain EBV-derived noncoding RNAs such as BamHI fragment A rightward transcript (BART) micro-RNAs (miRNAs) and EBV-encoded RNA. We focused on the exosome-mediated delivery of BART miRNAs. In vitro, BART miRNAs could induce the immune regulatory phenotype in macrophages characterized by the gene expressions of interleukin 10, tumor necrosis factor-α, and arginase 1, suggesting the immune regulatory role of BART miRNAs. The expression level of an EBV-encoded miRNA was strongly linked to the clinical outcomes in elderly patients with diffuse large B-cell lymphoma. These results implicate BART miRNAs as 1 of the factors regulating the severity of lymphoproliferative disease and as a diagnostic marker for EBV+ B-cell lymphoma.
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