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As part of an International Agency for Research on Cancer (IARC) international epidemiological study of workers in the pulp and paper industry, previously unpublished exposure measurements were assembled in a database. This article summarizes the results of 3,873 measurements carried out in the production departments of paper and paperboard mills and recycling plants in 12 countries. In the paper and paperboard mills, most of the agents were measured in the pulping and refining departments and in on-machine coating and winding of paper/paperboard. Exposures to asbestos, carbon monoxide, formaldehyde, fungal spores, bacteria, nitrogen dioxide, minerals dusts, paper dust, sulphuric acid and different solvents sometimes exceeded exposure limit values. In the re-pulping and de-inking departments of recycling plants high exposures to formaldehyde, fungal spores, bacteria and paper dust were observed. High exposures to asbestos, bioaerosols, carbon monoxide and paper dust were found in many departments; ammonia, formaldehyde, mineral and paper dust and solvents were found in coating machines; and diphenyl and polychlorobiphenyls (PCBs) were found in some special circumstances. Measurements in the newsprint and uncoated paper machine departments revealed only a few elevated exposures. In nearly all departments, measurements of epichlorohydrin, PCBs, sulphur dioxide, hydrogen sulphide and mercaptans tended to be low, often even below their detection limits. In spite of some uncertainties in the measurement data, the study provides new insights into the level and variation of occupational exposures of production workers in the paper and paperboard industry.

Objectives: Small-for-gestational-age (SGA) and large-for-gestational-age (LGA) births are major adverse birth outcomes related to newborn health. In contrast, the association between ambient air pollution levels and SGA or LGA births has not been investigated in Japan; hence, the purpose of our study is to investigate this association., Methods: We used birth data from Vital Statistics in Japan from 2017 to 2021 and municipality-level data on air pollutants, including nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ), photochemical oxidants, and particulate matter 2.5 (PM 2.5 ). Ambient air pollution levels throughout the first, second, and third trimesters, as well as the whole pregnancy, were calculated for each birth. The association between SGA/LGA and ambient levels of the air pollutants was investigated using crude and adjusted log-binomial regression models. In addition, a regression model with spline functions was also used to detect the non-linear association., Results: We analyzed data from 2,434,217 births. Adjusted regression analyses revealed statistically significant and positive associations between SGA birth and SO 2 level, regardless of the exposure period. Specifically, the risk ratio for average SO 2 values throughout the whole pregnancy was 1.014 (95% confidence interval [CI] 1.009, 1.019) per 1 ppb increase. In addition, regression analysis with spline functions indicated that an increase in risk ratio for SGA birth depending on SO 2 level was linear. Furthermore, statistically significant and negative associations were observed between LGA birth and SO 2 except for the third trimester., Conclusions: It was suggested that ambient level of SO 2 during the pregnancy term is a risk factor for SGA birth in Japan., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Improvements in medical treatment have contributed to rising health spending. Yet there is relatively little evidence on whether the spending increase is "worth it" in the sense of producing better health outcomes of commensurate value-a critical question for understanding productivity in the health sector and, as that sector grows, for deriving an accurate quality-adjusted price index for an entire economy. We analyze individual-level panel data on medical spending and health outcomes for 123,548 patients with type 2 diabetes in four health systems: Japan, The Netherlands, Hong Kong and Taiwan. Using a "cost-of-living" method that measures value based on improved survival, we find a positive net value of diabetes care: the value of improved survival outweighs the added costs of care in each of the four health systems. This finding is robust to accounting for selective survival, end-of-life spending, and a range of values for a life-year or fraction of benefits attributable to medical care. Since the estimates do not include the value from improved quality of life, they are conservative. We, therefore, conclude that the increase in medical spending for management of diabetes is offset by an increase in quality.

Objective: This prospective cohort study investigates the relationship between the onset of disability and employment status., Methods: We investigated 3,741 community-dwelling adults aged 70 or older, who participated in a population-based cohort study in Japan. Their onset of disability was monitored monthly using the long-term care insurance certification registration system, for five years from baseline. Based on an employment status questionnaire, we categorized participants into three groups: (1) employee, (2) self-employed, and (3) not working. Covariates included demographic information, medical history, number of medications, educational level, living alone, social group engagement, smoking status, walking speed, instrumental activities of daily living, global cognitive function, and depressive symptoms. Missing values were managed using multiple imputation. Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for incident disability risk by employment status., Results: The disability incidence rates were 15.3/1,000 (95% CIs: 10.7-22.0) person-years among employees, and 33.0/1000 (95% CIs: 24.4-44.6) and 39.6/1000 (95% CIs: 36.5-43.0) person-years among self-employed and non-working participants, respectively. The adjusted HRs for the onset of disability among non-working and self-employed participants were 1.69 (95% CIs: 1.16-2.46, p = 0.007) and 1.63 (95% CIs: 1.01-2.62, p = 0.044) compared with employees, respectively. Similar results were found among men. Among women, disability onset was not associated with employment status., Conclusions: Older adults' risk of disability onset differed according to their employment status. Older employees had a lower risk of disability onset than those not working or self-employed., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study aims to elucidate the risk factors of infertility treatment-associated harassment (I-harassment) among Japanese working women., Methods: The study participants were 1103 female patients who enrolled in the Japan-Female Employment and Mental Health in artificial reproductive technology (J-FEMA) study. Of the 1727 female patients, 1103 female patients were working during the initiation of infertility treatment and were still working during the survey. Risk factors for I-harassment were analyzed using a multivariable logistic regression model., Results: In this study, 82 female patients (7.4%) experienced I-harassment. The risk was significantly higher in those who had more in vitro fertilization (IVF) cycles than those who had fewer IVF cycles (OR, 1.06; 95% CI, 1.01-1.10). Similarly, those who disclosed their infertility treatment to their workplace were at significantly higher risk for I-harassment than those who did not (OR, 1.80; 95% CI, 1.03-3.15)., Conclusion: This study found that 7.4% of female patients experienced I-harassment after infertility treatment initiation. Those female patients who "experienced more IVF cycles," and "disclosed their infertility treatment in their workplace" should be carefully followed up by healthcare professionals to prevent I-harassment., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ambient dose equivalent conversion coefficients (ADC RCs ) for converting a radiocaesium inventory to ambient dose equivalent rates (air dose rates) depend on the vertical distribution of radiocaesium in soil. To access the validity of ADC RCs , the air dose rate at 1 m above ground and the vertical distribution of radiocaesium in the soil around the Fukushima Daiichi Nuclear Power Station (FDNPS) present between 2011 and 2019 were measured in the current study. ADC RCs were calculated using air dose rates and three different parameters representing the vertical distribution of radiocaesium in soil: (1) relaxation mass depth (β), (2) effective relaxation mass depth (β eff ) and (3) relaxation mass depth recommended by the International Commission on Radiation Units and Measurements before the FDNPS accident (β ICRU ). When ADC RCs based on β and β eff were compared to those based on β and β ICRU , a positive correlation was found. To confirm the applicability of the ADC RCs based on the three types of β values, radiocaesium inventories were estimated using the air dose rates and ADC RCs , and the obtained results were compared to the radiocaesium inventory calculated using soil sample measurements. Good agreement was observed between the radiocaesium inventories estimated using the ADC RCs based on β and β eff and measured by investigating soil samples. By contrast, the radiocaesium inventory estimated using the ADC RCs based on β ICRU was overestimated compared with that measured by investigating soil samples. These findings support the applicability of ADC RCs based on β and β eff in the Fukushima region. Furthermore, the β ICRU result suggests that differences in soil characteristics between Japan and other countries should be considered for evaluating ADC RCs ., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: We aimed to cross-sectionally investigate how work and sleep conditions could be associated with excessive fatigue symptoms as an early sign of Karoshi (overwork-related cerebrovascular and cardiovascular diseases; CCVDs)., Methods: We distributed a questionnaire regarding work, sleep, and excessive fatigue symptoms to 5410 truck drivers, as the riskiest occupation for overwork-related CCVDs, and collected 1992 total samples (response rate: 36.8%). The research team collected 1564 investigation reports required for compensation for Karoshi. Of them, 190 reports listed the prodromes of Karoshi, which were used to develop the new excessive fatigue symptoms inventory., Results: One-way analyses of variance showed that the excessive fatigue symptoms differed significantly by monthly overtime hours (p < 0.001), daily working time (p < 0.001), work schedule (p = 0.025), waiting time on-site (p = 0.049), number of night shifts (p = 0.011), and sleep duration on workdays (p < 0.001). Multivariate mixed-model regression analyses revealed shorter sleep duration as the most effective parameter for predicting excessive fatigue symptoms. Multiple logistic regression analysis confirmed that the occurrences of CCVDs were significantly higher in the middle [adjusted ORs = 3.56 (1.28-9.94)] and high-score groups [3.55 (1.24-10.21)] than in the low-score group., Conclusion: The findings suggested that shorter sleep duration was associated more closely with a marked increase in fatigue, as compared with the other work and sleep factors. Hence, ensuring sleep opportunities could be targeted for reducing the potential risks of Karoshi among truck drivers.

Polycyclic aromatic hydrocarbons (PAHs) were analyzed to elucidate the distribution, ecological risk, pathways, and fluxes of these pollutants in and around the Seto Inland Sea, an industrialized coastal region of Japan. High molecular weight PAHs (5-6 rings) were primarily found in regions close to the bay estuaries, and their proportions decreased at distances further from the estuaries (offshore areas), where low molecular weight PAHs (2-4 rings) were more ubiquitous. Screening-level risk assessments revealed that the PAHs found in the sediments should have no adverse effects on benthic communities. A mass balance for PAHs in the Seto Inland Sea, calculated based on data collected in the field and published literature findings, showed the PAH flux into the Seto Inland Sea from atmospheric deposition were ca. 6 times higher than that from riverine inflows. Comparison of the amount of the PAH mass flux between the Seto Inland Sea and the sea of the Europe and Asian countries indicated that the Seto Inland Sea is less polluted than the Gulf of Lion, the Mediterranean Sea, and the Bohai Sea, China and more polluted than the Yellow Sea. This paper is the first to determine the fluxes of PAHs in the coastal region of Japan., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The RIKEN BioResource Research Center (BRC) was established in 2001 as a comprehensive biological resource center in Japan. The Experimental Animal Division, one of the BRC infrastructure divisions, has been designated as the core facility for mouse resources within the National BioResource Project (NBRP) by the Japanese government since FY2002. Our activities regarding the collection, preservation, quality control, and distribution of mouse resources have been supported by the research community, including evaluations and guidance on advancing social and research needs, as well as the operations and future direction of the BRC. Expenditure for collection, preservation, and quality-control operations of the BRC, as a national core facility, has been funded by the government, while distribution has been separately funded by users' reimbursement fees. We have collected over 9000 strains created mainly by Japanese scientists including Nobel laureates and researchers in cutting-edge fields and distributed mice to 7000 scientists with 1500 organizations in Japan and globally. Our users have published 1000 outstanding papers and a few dozen patents. The collected mouse resources are accessible via the RIKEN BRC website, with a revised version of the searchable online catalog. In addition, to enhance the visibility of useful strains, we have launched web corners designated as the "Mouse of the Month" and "Today's Tool and Model." Only high-demand strains are maintained in live colonies, while other strains are cryopreserved as embryos or sperm to achieve cost-effective management. Since 2007, the RIKEN BRC has built up a back-up facility in the RIKEN Harima branch to protect the deposited strains from disasters. Our mice have been distributed with high quality through the application of strict microbial and genetic quality control programs that cover a globally accepted pathogens list and mutated alleles generated by various methods. Added value features, such as information about users' publications, standardized phenotyping data, and genome sequences of the collected strains, are important to facilitate the use of our resources. We have added and disseminated such information in collaboration with the NBRP Information Center and the NBRP Genome Information Upgrading Program. The RIKEN BRC has participated in international mouse resource networks such as the International Mouse Strain Resource, International Mouse Phenotyping Consortium, and Asian Mouse Mutagenesis and Resource Association to facilitate the worldwide use of high-quality mouse resources, and as a consequence it contributes to reproducible life science studies and innovation around the globe., (© 2021. The Author(s).)

Rationale: As a species, humans are vulnerable to numerous mental disorders, including depression and schizophrenia. This susceptibility may be due to the evolution of our large, complex brains, or perhaps because these illnesses counterintuitively confer some adaptive advantage. Additionally, cultural and biological factors may contribute to susceptibility and variation in mental illness experience and expression. Taking a holistic perspective could strengthen our understanding of these illnesses in diverse cultural contexts., Objectives: This paper reviews some of these potential factors and contextualizes mental disorders within a biocultural framework., Results: There is growing evidence that suggests cultural norms may influence inflammation, neurotransmitters, and neurobiology, as well as the illness experience. Specific examples include variation in schizophrenia delusions between countries, differences in links between inflammation and emotion between the United States and Japan, and differences in brain activity between Caucasian and Asian participants indicating that cultural values may moderate cognitive processes related to social cognition and interoception., Conclusions: Research agendas that are grounded in an appreciation of biocultural diversity as it relates to psychiatric illness represent key areas for truly interdisciplinary research that can result in culturally sensitive treatments and highlight possible biological variation affecting medical treatment.

This paper analyses whether government ideology and other political- and electoral-related factors influence country-level public healthcare expenditures, focussing on the impact of the Great Recession on that relationship. We test this hypothesis for the OECD countries in 1970-2016. Our results reveal the presence of a partisan effect, left-wing governments being more likely to raise public expenditures in the health sector. We also find that coalitions increase these expenditures, whilst minority governments and those with a high presence in the lower house decrease them. Meanwhile, the opportunistic behaviour of incumbents related to the timing of elections is not supported by our results. The percentage of public expenditures over total health expenditures is also examined, obtaining similar results regarding the partisan effect. However, the onset of the Great Recession has altered these relationships, neutralizing the impact of political factors.

A number of studies assessed the association of ring finger protein 213 (RNF213) gene polymorphisms with moyamoya disease (MMD), but the results were not entirely consistent. This meta-analysis was performed to explore the relationship between RNF213 polymorphisms and moyamoya disease in Asian population. A systematic search from the PubMed, MEDLINE, EMBASE, ISI web of science, CNKI, China CBM and WANFANG DATA databases was conducted to retrieve published studies until March 2015. Statistical analyses were performed using the STATA12.0 software. Fixed or random effects model, subgroup analysis, sensitivity analysis, and publication bias were used to improve the comprehensive analysis. Eight papers including 904 MMD patients and 2258 controls were recruited in the meta-analysis. rs112735431 was closely associated with the risk of MMD among Asian population in all genetic models (dominant model: OR 103.39, 95 % CI 52.25-204.55, P = 1.69e-40; recessive model: OR 16.45, 95 % CI 6.00-45.10, P = 5.33e-08; additive model: OR 61.49, 95 % CI 22.07-171.33, P = 3.32e-15), especially in the Japanese population. Subgroup analysis revealed highly statistically significant higher risk in the patients with family histories. Although another polymorphism rs148731719 showed no significant association with the MMD, rs138130613 was found to be related to the higher risk in Chinese population (dominant model: OR 8.34, 95 % CI 1.72-40.47, P = 0.008). Our meta-analysis strengthens RNF213 rs112735431 is closely associated with the increased risk of MMD in Japanese, and the screening combined with rs112735431 and rs138130613may improve the detection rate for MMD in China.

Analyses of the Life Span Study (LSS) of Japanese atomic bombing survivors have routinely incorporated corrections for additive classical measurement errors using regression calibration. Recently, several studies reported that the efficiency of the simulation-extrapolation method (SIMEX) is slightly more accurate than the simple regression calibration method (RCAL). In the present paper, the SIMEX and RCAL methods have been used to address errors in atomic bomb survivor dosimetry on solid cancer and leukaemia mortality risk estimates. For instance, it is shown that using the SIMEX method, the ERR/Gy is increased by an amount of about 29 % for all solid cancer deaths using a linear model compared to the RCAL method, and the corrected EAR 10(-4) person-years at 1 Gy (the linear terms) is decreased by about 8 %, while the corrected quadratic term (EAR 10(-4) person-years/Gy(2)) is increased by about 65 % for leukaemia deaths based on a linear-quadratic model. The results with SIMEX method are slightly higher than published values. The observed differences were probably due to the fact that with the RCAL method the dosimetric data were partially corrected, while all doses were considered with the SIMEX method. Therefore, one should be careful when comparing the estimated risks and it may be useful to use several correction techniques in order to obtain a range of corrected estimates, rather than to rely on a single technique. This work will enable to improve the risk estimates derived from LSS data, and help to make more reliable the development of radiation protection standards.

This paper analyzes the importance of the German language and German culture and institutional development of urology in Japan in the early 20th century, starting from the development of the medical school for Japanese in Germany and their function in the process of modernization of the Meiji period (1868-1912). Examples of bi-directional German-Japanese relations in medicine, which also included an integrated knowledge transfer, are shown. The study is based mainly on Japanese and German sources about Japanese physicians in Germany as well as contemporary publications in German and international medical journals. Methodologically, the article combines quantitative analysis with individual biographical aspects.

Invasion of alien species has been shown to cause detrimental effects on habitats of native species. Insect pollinators represent such examples; the introduction of commercial bumble bee species for crop pollination has resulted in competition for an ecological niche with native species, genetic disturbance caused by mating with native species, and pathogen spillover to native species. The European honey bee, Apis mellifera, was first introduced into Japan for apiculture in 1877, and queen bees have been imported from several countries for many years. However, its effects on Japanese native honey bee, Apis cerana japonica, have never been addressed. We thus conducted the survey of honey bee viruses and Acarapis mites using both A. mellifera and A. c. japonica colonies to examine their infestation in native and non-native honey bee species in Japan. Honey bee viruses, Deformed wing virus (DWV), Black queen cell virus (BQCV), Israeli acute paralysis virus (IAPV), and Sacbrood virus (SBV), were found in both A. mellifera and A. c. japonica colonies; however, the infection frequency of viruses in A. c. japonica was lower than that in A. mellifera colonies. Based on the phylogenies of DWV, BQCV, and SBV isolates from A. mellifera and A. c. japonica, DWV and BQCV may infect both honey bee species; meanwhile, SBV has a clear species barrier. For the first time in Japan, tracheal mite (Acarapis woodi) was specifically found in the dead honey bees from collapsing A. c. japonica colonies. This paper thus provides further evidence that tracheal-mite-infested honey bee colonies can die during cool winters with no other disease present. These results demonstrate the infestation of native honey bees by parasite and pathogens of non-native honey bees that are traded globally.

Estimation of radionuclide concentrations in trees may be required to estimate their radiation exposure. However, concentration ratios of radionuclides from soil to tree species are limited for many radionuclide-tree combinations. To fill this gap, it is investigated in the present paper whether stable element concentration data for leafy vegetables are representative of those for wild tree leaves, and consequently, if these stable element data for leafy vegetables can be used as analogues to describe radionuclides transfer from soil to trees. Data for stable elements in leafy vegetables collected in Japan were compared with those in leaves of about 20 tree species worldwide. The correlation coefficients of element concentrations between leafy vegetables and tree leaves were higher than 0.90 with p < 0.001 by Student's t test, and geometric means of concentration data for most elements were within the range of data for leafy vegetables. Thus, transfer parameters derived from stable element data for leafy vegetables could generally be used to estimate concentrations in tree leaves if data for the latter are not available. However, some trees accumulate a few elements (e.g., Al, Co, Mn and Si) in their leaves to higher concentrations than observed for leafy vegetables.

This paper presents the occurrence, distribution, and environmental impact of pesticide residues in coastal water in southern Japan that receives effluents from a wastewater reservoir temporarily storing surface runoffs of rice paddy fields located near the coastline during the 2005 rice planting season. Concentrations of 14 target pesticides were measured by GC-MS and the hazards posed by the most important pesticides detected were evaluated by acute toxicity tests using a marine diatom, Chaetoceros sp., and a marine amphipod, Hyale barbicornis. Six pesticides (fenobucarb, flutolanil, iprobenfos, mefenacet, phthalide, pyriproxyfen) were detected in the coastal water, with three pesticides (fenobucarb, iprobenfos, and mefenacet) having 100% frequencies of detection. The maximum concentration of mefenacet, at 4.22 microg/L, was at least one magnitude higher than that of fenobucarb and iprobenfos, at 0.27 and 0.19 microg/L, respectively, while the three remaining pesticides had concentrations just around the detection limit of 0.01 microg/L. Consequently, detected concentrations of mefenacet were highly correlated with salinity levels, confirming that the wastewater reservoir is a major source of rice pesticide residues in this particular coastal environment. Hence, the spatial distribution of mefenacet was simulated using their relationship and the results indicate that mefenacet has a tendency to enter and spread to a relatively wide portion of the coastal area during the rice planting season. There is also a possibility that the other pesticides used in rice farming such as fenobucarb and iprobenfos may show similar distribution patterns in coastal waters when they are present in the wastewater reservoir at higher concentrations. These pesticides, however, manifested low acute toxicities to both Chaetoceros sp. and H. barbicornis, suggesting little impact to marine organisms.

Nervous system development in echinoderms has been well documented, especially for sea urchins and starfish. However, that of crinoids, the most basal group of extant echinoderms, has been poorly studied due to difficulties in obtaining their larvae. In this paper, we report nervous system development from two species of crinoids, from hatching to late doliolaria larvae in the sea lily Metacrinus rotundus and from hatching to cystidean stages after settlement in the feather star Oxycomanthus japonicus. The two species showed a similar larval nervous system pattern with an extensive anterior larval ganglion. The ganglion was similar to that in sea urchins which is generally regarded as derived. In contrast with other echinoderm and hemichordate larvae, synaptotagmin antibody 1E11 failed to reveal ciliary band nerve tracts. Basiepithelial nerve cells formed a net-like structure in the M. rotundus doliolaria larvae. In O. japonicus, the larval ganglion was still present 1 day after settlement when the adult nervous system began to appear inside the crown. Stalk nerves originated from the crown and extended down the stalk, but had no connections with the remaining larval ganglion at the base of the stalk. The larval nervous system was not incorporated into the adult nervous system, and the larval ganglion later disappeared. The aboral nerve center, the dominant nervous system in adult crinoids, was formed at the early cystidean stage, considerably earlier than previously suggested. Through comparisons with nervous system development in other ambulacraria, we suggest the possible nervous system development pattern of the echinoderm ancestor and provide new implications on the evolutionary history of echinoderm life cycles.

An earlier analysis examined the possibility of bias in the Life Span Study (LSS) cohort by studying Japanese A-bomb survivors with bomb-related acute injuries and those without such injuries. The authors reported significantly higher radiation risks, both for cancers and non-cancers, among those survivors with acute injuries compared with those without. The risks were reported to be particularly large among survivors aged <10 or > or =55 years of age at the time of bombings. The aim of this paper is to examine these findings more closely using the LSS acute effects data. All the analyses were carried out using Poisson regression. Relative risk models were fitted with adjustment for sex and other factors. Significant differences in relative risk between survivors with epilation and burns and those without epilation and burns are found for leukaemia. There is also some evidence for heterogeneity in the leukaemia risk between survivors with two or more acute injuries and those with no injuries, but the evidence is disappeared when survivors with one or more injuries are compared with those without injuries. For solid cancers, cardiovascular disease and all deaths combined, the risks do not differ to a statistically significant extent between survivors with and without injuries. There is no statistically significant heterogeneity in risk across age-at-exposure categories for survivors with injuries. For all deaths combined, relative risk estimates and their uncertainties are significantly higher for survivors exposed at ages <10 years when compared with other exposure ages, but risks are not significantly raised for survivors exposed at > or =55 years of age. With the exception of leukaemia, the findings from the present work are inconsistent with those of Stewart and Kneale.

An enhanced attenuated strain of Pepper mild mottle virus (PMMoV) was constructed by incorporating mutations that affect viral attenuation from three reported attenuated strains of PMMoV, which causes serious economic losses in the production of green pepper in Japan. The new strain caused no symptoms on pepper plants and protected them from infection by a wild-type strain. The mutations responsible for viral attenuation were located in the intervening region (IR) of the 126-kDa/183-kDa proteins. The mutations had synergistic effects in terms of the attenuation of symptoms and decreased the accumulation of the viral coat protein in infected pepper plants. In this paper, we propose an efficient method for the improvement of attenuated viruses by reverse genetics in plant viruses.

The long-lived radioisotope (36)Cl (half-life: 301,000 years) was measured in granite samples exposed to A-bomb neutrons at distances from 94 to 1,591 m from the hypocenter in Hiroshima, by means of accelerator mass spectrometry (AMS). Measured (36)Cl/Cl ratios decrease from 1.6 x 10(-10) close to the hypocenter to about 1-2 x 10(-13), at a distance of 1,300 m from the hypocenter. At this distance and beyond the measured (36)Cl/Cl ratios do not change significantly and scatter around values of 1-2 x 10(-13). These findings suggest that the (36)Cl had been predominantly produced by thermalized neutrons from the A-bomb via neutron capture on stable (35)Cl, at distances from the hypocenter smaller than about 1,200 m. At larger distances, however, confounding processes induced by cosmic rays or neutrons from the decay of uranium and thorium become important. This hypothesis is theoretically and experimentally supported in a consecutive paper. The results are compared to calculations that are based on the most recent dosimetry system DS02. Close to the hypocenter, measured (36)Cl/Cl ratios are lower than those calculated, while they are significantly higher at large distances from the hypocenter. If the contribution of the cosmic rays and of the neutrons from the decay of uranium and thorium in the sample was subtracted, however, no significant deviation from the DS02 calculations was observed, at those distances. Thus, the Hiroshima neutron discrepancy reported in the literature for (36)Cl for samples from large distances from the hypocenter, i.e., higher measured (36)Cl/Cl ratios than predicted by the previous dosimetry system DS86, was not confirmed.

Intrathecal baclofen therapy (ITB therapy) is useful for severe spasticity. However, the Ministry of health, labour and welfare has not allowed the therapy in Japan. A clinical trial of intrathecal baclofen therapy is currently under way. In this paper the situation in Japan with regard to ITB therapy is described and information for physicians in Japan given from our experience. Team approach is important for ITB therapy. Special attention should be paid to patient selection.

Objectives: During the period of technological innovation and rapid economic development, portable power tools were introduced on a large scale in Japan. Vibration disease from the operation of those tools and its prevention and therapy became urgent social problems in the 1970s. This paper aims to introduce national regulations in Japan for diagnostics in the health surveillance, certification, therapy and compensation of vibration disease and evaluates them in the present perspective., Method: Relevant laws, regulations and administrative directives were described in chronological order. Effect of those laws, regulations and directives were evaluated by statistics., Results: Relevant regulations were established in 1947 and were revised in the 1960s and 1970s. According to those regulations, administrative directives were issued. Relevant vibration-disease statistics improved from the 1970s to 1990s. The annual ratio of workers examined was 95% to 100% in national forests (NFs), 47.3% in 1980 and 40.8% in 1990 in private industry (PI). The number of workers certified in NFs was 1,796 from 1971-1975, with a decrease to nine from 1991-1995, while in PI there were 9,783 from 1976-1980, decreasing to 2,331 from 1991-1995. However, in the construction industry the number increased again in the 1990s. The top four workers certified by the type of tool from 1994-1997 were operators of rock drills, chainsaws, pick hammers and concrete vibrators. The annual number of workers under treatment (at highest level) was 3,605 (1982; NFs) and 13,501 (1987; PI), with a decrease to 3,481 (1997; NFs) and 8,958 (1997; PI). Regulations for compensation covered 3,670 workers from 1965 to 1997 (NFs) and 22,723 from 1976 to 1997 (PI) in medical treatment benefits, and 189 (NFs) and 15,448 (PI) in disability benefits during the same term., Conclusion: The national regulations developed in Japan since 1965 for health surveillance, certification, therapy and compensation of hand-transmitted vibration disease have proven effective for prevention and compensation of vibration disease in many industries, but unsolved problems remain in the construction industry.

Objectives: This paper evaluates the associations of previous exposure to environmental cadmium (Cd) and renal function with total mortality and cancer incidence., Methods: The study population comprised 275 residents (aged 40-92 years at baseline) in a Cd-polluted area located on Tsushima Island, Nagasaki, Japan. In the study area, the dietary intake of Cd decreased because the soil of the Cd-polluted rice fields was replaced with new soil between 1980 and 1983. The mortality rate from 1982 to 1997 and cancer incidence from 1985 to 1996 were investigated. Standardized mortality and incidence ratios (SMR and SIR) were calculated by using regional reference rates. The associations of renal function and urinary Cd levels with total mortality and cancer incidence were evaluated with Cox regression models., Results: The SMR for all subjects, and those with a urinary beta2-microglobulin (U-beta2M) concentration > or = 1,000 microg/g creatinine (Cr) and < 1,000 microg/g Cr was estimated at 90 [95% confidence interval (CI) 73-109], 138 (95% CI 101-183) and 66 (95% CI 49-87), respectively. After adjustment for age and other potential confounders, in men, serum beta2M (S-beta2M) (> or = 2.3 mg/l) and in women, serum Cr (> or = 21.2 mg/ 100 ml), relative clearance of beta2M (> or = 21%) and U-beta2M (> or = 1,000 microg/g Cr), were associated with a significantly increased risk of mortality, with hazard ratios exceeding 2.0. After further adjustment for log(U-beta2M), the rate ratio of deaths associated with, in men, increased S-beta2M was 2.53 (95% CI 0.97-6.65) and, in women, increased serum Cr (S-Cr) concentrations was 2.75 (95% CI 1.24-6.14). Urinary Cd concentrations (> or = 10 microg/g Cr) were not significantly associated with mortality. The overall SIR of all malignant neoplasms was 71 (95% CI 44-107)., Conclusions: These findings suggest that renal tubule dysfunction and a reduced glomerular filtration rate are predictors of mortality among persons previously exposed to environmental Cd. However, the results also suggest that overall mortality rates in Cd-polluted areas are not necessarily increased, because of the low mortality among those with no, or only slight, signs of low-molecular weight proteinuria. Overall cancer incidence may not be increased among residents in Cd-polluted areas.

Chronic myeloid leukemia (CML) invites biologically based radiation risk modeling because CML is simultaneously well-understood, homogeneous and prevalent. CML is known to be caused by a translocation involving the ABL and BCR genes, almost all CML patients have the BCR-ABL translocation, and CML is prevalent enough that its induction is unequivocally detected among Hiroshima A-bomb survivors. In a previous paper, a linear-quadratic-exponential (LQE) dose-response model was used to estimate the lifetime excess risk of CML in the limit of low doses of gamma-rays, R gamma. This estimate assumed that BCR-ABL translocation dose-response curves in stem cells for both neutrons and gamma-rays, differ only by a common proportionality constant from dicentric aberration dose-response curves in lymphocytes. In the present paper we challenge this assumption by predicting the BCR-ABL dose response. The predictions are based on the biophysical theory of dual radiation action (TDRA) as it applies to recent BCR-to-ABL distance data in G0 human lymphocytes; this data shows BCR and ABL geometric distributions that are not uniform and not independent, with close association of the two genes in some cells. The analysis speaks against the previous proportionality assumption. We compute 11 plausible LQE estimates of R gamma, 2 based on the proportionality assumption and 9 based on TDRA predictions. For each estimate of R gamma we also compute an associated estimate of the number of CML target cells, N; the biological basis of the LQE model allows us to form such estimates. Consistency between N and hematological considerations provides a plausibility check of the risk estimates. Within the group of estimates investigated, the most plausible lifetime excess risk estimates tend to lie near R gamma = 0.01 Gy-1, substantially higher than risk estimates based on the proportionality assumption.

In this paper we describe female workers' health care, the women's and maternal protection system within the Japanese legal system, the current status of female workers in Japan, and problems regarding methods of advancing health care and the women's or maternal protection system. Motherhood is respected in the workplace in Japan, and in order to provide an environment in which women can work and still bear and rear children with a sense of security, laws concerning maternal protection of female workers, and revisions in terms of the system have been made, and a new system has been in effect since the fiscal year of 1998. Nevertheless, gender discrimination against women and the disparagement of women, rooted in gender role stereotypes concerning the division of labor, remain firmly planted in the social environment and in long-established custom.

Objectives: A previous extensive review of the literature including that from the middle of 1992 concluded that whole-body vibrations may contribute to low back pain, but that the exposure-response relationship had not been clarified. We reviewed the literature of the past 7 years to find out: (i) whether there is evidence in the recent epidemiological literature for a causal association between whole-body vibrations and low back pain, and (ii) if there is evidence in the recent literature for a dose-response relationship between whole-body vibrations and low back pain., Methods: All relevant epidemiological articles which were obtained through a search in the databases MEDLINE, OSH-ROM and TOXLINE, and through personal communication, were reviewed independently by the two authors, using a checklist., Results: Twenty-four original articles concerning the association between whole-body vibrations and the lower back were retained for use. The quality of the papers was mostly low, but improved with time. Only seven articles passed our predetermined quality criteria. Of the seven reports, one showed increased frequency of lumbar prolapse in occupational drivers, and six showed low back pain to be more frequent in whole-body vibration-exposed groups. Only two out of the four articles reporting on dose, showed a dose-response association., Conclusions: Despite the lack of definite evidence, we found sufficient reasons for the reduction of whole-body vibration-exposure to the lowest possible level. If new knowledge is to be produced, good prospective studies with repeated measurements of exposure, analyses of work postures, and clear definitions and subgroupings of low back pain are needed. Other research in this field should be given up, and the resources used for more important issues, as the size of the problem of whole body vibration is probably on the decrease because of the technical prophylactic developments that are already in progress.

Objectives: To evaluate Japanese occupational health services (OHSs) for small-scale enterprises (SSEs)., Methods: The current Japanese OHSs for SSEs were compared with 15 recommendations of the Joint WHO/ILO Task Group. The status of OHSs was analyzed using the published papers collected by means of a computerized literature search. Thirty-five papers were used in the analysis, which was first conducted by the four authors separately, followed by discussion among the authors. Evaluation was conducted by classifying the status of Japanese OHSs for SSEs into three classes (A: good, B: average, C: poor) based on comparison with each recommendation., Results: Six issues were evaluated as "A": establishment of a national policy for the provision of OHSs for SSEs, occupational health and safety inspection for SSEs, legislation to ensure services for SSEs and provision of financial incentives, adoption of occupational health programs using multiple channels, training in occupational health issues, and establishment of national data collection and registration systems. Nine issues were evaluated as "B": provision of OHSs for all SSEs as a part of the "national Health for ALL" strategy, intervention combining economic development and OHSs, extension of OHSs to vulnerable groups, coverage of migrant and seasonal workers by OHSs, the establishment of a national collaborative and coordinative body on OHSs, control of transfer of hazardous technology, encouragement of applied research, employers' commitment and worker participation, and integration of OHSs with primary health care. None of them was evaluated as "C"., Conclusions: Japanese OHSs for SSEs were fairly well established in terms of compliance with the recommendations of the Joint WHO/ILO Task Group, although evaluation may be somewhat subjective and rather qualitative.

L-DOPA therapy for Parkinson's disease is one of the major achievements of twentieth century neurology; Parkinson's disease was the first in which specific neurochemical deficits in defined brain regions were identified, and thus for which a rational, chemical therapy could be developed, ushering in the era of clinical neurochemistry. The contributions of Birkmayer and Hornykiewicz (Vienna), Barbeau and Sourkes (Montreal) and of Cotzias (New York) to this story are well-known. Almost completely forgotten, on the other hand, is a paper presented by the Japanese neurologist Isamu Sano in 1960 which reported what is probably the first attempt to treat Parkinson's disease patients with DOPA. This is all the more remarkable as the author was also responsible for one of the key papers which led to the use of DOPA in Parkinson's disease by other workers. Despite the negative outcome of his experience with L-DOPA, Sano deserves to be remembered as one of the pioneers in catecholamine research, having been the first to map dopamine levels in the human brain, and identified the reduction of dopamine levels in the substantia nigra and striatum in Parkinson's disease.

In this paper the radiation-associated relative risks of second primary cancer incidence in groups treated for first primary cancer by radiotherapy are compared with radiation-associated relative risk estimates in the Japanese atomic bomb survivor cancer incidence data. For four cancer sites, namely lung cancer, bone cancer, ovarian cancer and leukaemia, the relative risks in the comparable (age at exposure, time since exposure, sex matched) subsets of the Japanese data are significantly greater than those in the majority of second cancer studies. Even when the differences between the relative risks in the Japanese atomic bomb survivors and the medical series do not approach conventional levels of statistical significance, relative risks tend to be higher in the Japanese data than in the second cancer studies. At least for leukaemia, the discrepancy between the Japanese and second cancer risks can be largely explained by cell-sterilisation effects. There are few indications of modification of radiation-associated second cancer relative risk among those treated with adjuvant chemotherapy, nor are there strong indications of modification of radiation-associated relative risk by heritable genetic factors. If anything, there is evidence that second cancer relative excess risks are lower among those patients with cancer-prone disorders than among non-susceptible patients. However, the higher underlying cancer risk in some of these medically exposed populations should also be considered, in particular for those with cancer-prone conditions, so that the absolute excess risk is sometimes higher than in the Japanese data.

Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant cerebellar ataxia characterized clinically by myoclonus, epilepsy, cerebellar ataxia, choreoathetosis, and dementia with personality change. Histopathologically, DRPLA is characterized by a unique combination of degenerative changes in both the dentatofugal and the pallidofugal systems. Credit for the establishment of DRPLA as an entity is given to Naito and Oyagagi, who first noticed a strong heritability and an age of onset-dependent variability of the clinical features. Most papers on DRPLA research are written in Japanese, and are extensively reviewed here. After the gene was identified in 1994, DRPLA became known as one of the CAG repeat expansion diseases, in which the responsible gene is located on chromosome 12p and its product is called atrophin-1. Classical genetics revealed that DRPLA shows prominent "anticipation" and modern molecular genetics provided a clear explanation for this phenomenon, by demonstrating a strong instability of the expanded CAG repeat length through generations. The impact of gene analysis of DRPLA on the clinical genetics and neurology are discussed. Moreover, possible mechanism(s) underlying the neuronal cell death in DRPLA are discussed in terms of the molecular pathology.

"The aim of this paper is to illuminate basic characteristics of metropolitan areas in Japan. [The authors] first delineate the boundaries of ninety-eight Japanese metropolitan areas based on the concept of cut-off point on the P-M curve the idea of which was originally developed by Ogawa in 1957. Secondly, [they] carry out empirical analyses on spatial structure and growth patterns of those metropolitan areas by use of 1960 and 1975 data." The results indicate that the population share of central cities declined from 1960 to 1975., (excerpt)