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This longitudinal study examined the relationship between flexibility-activity and blood-pressure (BP) change among older adults in Japan. Our study included 452 older adults who took part in our survey in both 2012/2013 and 2017/2018. The seated systolic blood pressure (SBP) and diastolic BP (DBP) were measured both at baseline and at the 5 years follow-up. The frequencies of the different physical activities at baseline were assessed using a questionnaire. A generalized linear mixed model was used to estimate the non-standardized coefficient (B) of BP change associated with flexibility activity, after adjustments for sex, age, body mass index, smoking status, alcohol consumption, antihypertensive medication use, history of heart disease, walking time, and muscle-strengthening activity as a fixed-effect, and area of residence as a random-effect. Higher flexibility-activity frequency was significantly associated with reduced SBP (B = -0.77 [95% confidence intervals = -1.36, -0.18], p for linear trend = 0.01, p for quadratic trend = 0.85) and DBP (-0.33 [-0.71, 0.05], p for linear trend = 0.09, p for quadratic trend = 0.04). Engaging in flexibility activity for 3 days per week was significantly associated with a reduction in DBP (B = -4.16, 95% CI [-7.53, -0.79], p = 0.02) compared with that in the reference group (0 days per week). Interaction tests were not significant between basic variables (sex, age, BMI, and antihypertensive medication) and flexibility. In conclusion, higher flexibility activity frequency was associated with a reduction in BP in older adults. Future longitudinal and interventional studies should examine the effects of flexibility activity on cardiovascular disease prevention., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Measuring implementation outcomes for digital mental health interventions is essential for examining the effective delivery of these interventions. The "Implementation Outcome Scale of Digital Mental Health" (iOSDMH) has been validated and used in several trials. This study aimed to compare the iOSDMH for participants in six randomized controlled trials (RCTs) involving web-based interventions and to discuss the implications of the iOSDMH for improving the interventions. Additionally, this study examined the associations between iOSDMH scores and program completion rate (adherence)., Methods: Variations in total scores and subscales of the iOSDMH were compared in six RCTs of digital mental health interventions conducted in Japan. The web-based intervention programs were based on cognitive behavioral therapy (2 programs), behavioral activation (1 program), acceptance and commitment (1 program), a combination of mindfulness, behavioral activation, and physical activity (1 program), and government guidelines for suicide prevention (1 program). Participants were full-time employees (2 programs), perinatal women (2 programs), working mothers with children (1 program), and students (1 program). The total score and subscale scores were tested using analysis of variance for between-group differences., Results: Total score and subscale scores of the iOSDMH among six trials showed a significant group difference, reflecting users' perceptions of how each program was implemented, including aspects such as acceptability, appropriateness, feasibility, overall satisfaction, and harm. Subscale scores showed positive associations with completion rate, especially in terms of acceptability and satisfaction (R-squared = 0.93 and 0.89, respectively)., Conclusions: The iOSDMH may be a useful tool for evaluating participants' perceptions of features implemented in web-based interventions, which could contribute to improvements and further development of the intervention.

Background: The Olympic Games represent an opportunity to create a 'physical activity legacy' that promotes physical activity at the population level in the host nations and cities. However, previous studies showed little increase in population-level physical activity following the Olympics. The upsurge of public interest in sports and physical activity participation before the Olympics may diminish rapidly following the Games. We examined the pre-Games effects of the Olympics on Japanese population-level physical activity after the announcement of Tokyo's successful bid for the 2020 Olympic and Paralympic Games in September 2013., Methods: We used publicly available data from serial cross-sectional surveys conducted with nationally or regionally representative samples in Japan seven years before and after the announcement (from 2006-2020). The outcomes were 1) daily step counts and 2) exercise habit prevalence (≥ 30 min/day, ≥ 2 days/week, and over a year) from the National Health and Nutrition Surveys Japan (NHNS-J; 14 time points; aggregated data); and 3) sports participation (at least once a week) from the National Sports-Life Survey conducted every two years (NSLS; eight time points; individual-level data of 18,867 adults) and from the Public Opinion Survey on Sports Participation of Tokyo Residents (POSSP; eight time points; aggregated data). Age- and gender-adjusted regression models were used to estimate changes in the outcomes before and after the announcement., Results: There were no significant pre-Games effects of the Olympics on national-level physical activity participation among Japanese adults. Sports participation (56.4% and 57.5%, respectively; P = 0.518), daily steps (6,535 and 6,686 steps/day; P = 0.353), and exercise habit (30.7% and 29.1%, P = 0.309) did not change significantly before and after the announcement. Although an increase in sports participation among Tokyo residents was not found in the NSLS (61.5% and 59.3%, P = 0.227), it was observed in the POSSP (49.1% and 57.7%, P = 0.019). Nonetheless, this increase might not be related to the pre-Games effects since the trend diminished following the announcement., Conclusions: Population-level physical activity did not show significant changes until 2020. Realising the physical activity legacy of an Olympics may require strategic promotion and cross-agency partnership implementation in the pre- and post-event period., (© 2022. The Author(s).)

Background: Food access is an important aspect of health promotion for the elderly. The aim of this study was to investigate the relationship between distance to the nearest food store and diet variety in rural community-dwelling elderly Japanese., Methods: This cross-sectional study analyzed data from 1,103 elderly participants surveyed by mail in rural areas of Japan. Diversity of food intake was assessed using the diet variety score (DVS). Street network distance from home to food store was calculated and categorized by quartile using a geographic information system and analyzed in relation to diet using multivariable regression with the primary outcome as low DVS. Sub-analysis of the association with DVS was conducted for each food store category (convenience store, supermarket, and small food store). The association between intake frequency of each food group and distance was also analyzed., Results: Participants in the fourth quartile of distance to food store had significantly higher prevalence ratio (1.15; 95% CI, 1.01-1.32) for low DVS than those in the first quartile. There was a significant tendency between greater distance to food store and lower DVS (P for trend = 0.033). Supermarkets and convenience stores, in particular, showed significant associations. Greater distance was significantly associated with lower frequency of meat and fruit intake., Conclusion: There was significant association between distance to nearest food store and diet variety in rural Japanese elderly. These findings suggest the importance of interventions for areas at high risk of low diet variety, such as places far away from food stores.

Background: Physical inactivity during the coronavirus disease 2019 (COVID-19) pandemic may have hindered the development of fundamental movement skills in preschoolers. This serial cross-sectional study compared fundamental movement skills by age group before and during the COVID-19 pandemic (2019-2020), among Japanese preschoolers aged 3-5 years., Methods: Of the 22 preschools within Unnan City, Shimane Prefecture, Japan, 21 (95.5%) and 17 (77.3%) participated in the 2019 and 2020 surveys, respectively. We analyzed 608 and 517 preschoolers in both surveys. Fundamental movement skills were objectively assessed with a 25 m run, standing long jump, and softball throw, based on the Japanese physical activity guidelines for preschoolers. Mann-Whitney U tests were used to compare the fundamental movement skills data between periods., Results: For the 25 m run, participants aged 5 years were faster before than during the pandemic (p = 0.018), while participants aged 3 and 4 years showed no significant differences. Participants aged 3-5 years showed no significant differences before and during the pandemic for the standing long jump (p ≥ 0.072). For the softball throw, all grades scored higher before than during the pandemic (p < 0.001)., Conclusions: These findings suggest that the COVID-19 pandemic impeded the development of fundamental motor skills, especially for object control skills. This highlights the need for interventions aimed at developing fundamental motor skills in preschoolers during and after the pandemic.

Purpose: This cross-sectional study investigated the association between hilliness and walking speed in community-dwelling older adults, and whether it varied according to their car-driving status., Methods: Data were collected from 590 participants aged 65 and older living in Okinoshima Town, Shimane prefecture, Japan, in 2018. Comfortable walking speed (m/s) was objectively assessed. Hilliness was measured by the mean land slope (degree) within a 500-m or 1000-m network buffer around each participant's home using a geographic information system. A multiple linear regression examined whether the land slope was associated with walking speed, adjusted for sex, age, body mass index, smoking habits, alcohol consumption habits, exercise habits, chronic disease, and living arrangements. A stratified analysis by car-driving status was also conducted., Results: After adjusting for all confounders, the land slope within the 500-m or 1000-m network buffer was negatively associated with walking speed (B = -0.007, 95% CI [-0.011, -0.002]; B = -0.007, 95% CI [-0.011, -0.003], respectively). The stratified analysis by car-driving status showed that living in a hilly area was negatively associated with walking speed among non-drivers in the 500-m or 1000-m network buffer (B = -0.011, 95% CI [-0.017, -0.004]; B = -0.012, 95% CI [-0.019, -0.006]), though there were no associations among drivers., Conclusions: A hilly environment is positively associated with slow walking speed in community-dwelling older adults in Japan. Moreover, car-driving status potentially modifies the relationship between living in a hilly environment and slow walking speed., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: In Japan, public dialogue on allocation of life-saving medical resources remains taboo, and discussion largely has been avoided., Research Question: Do Japanese health care workers and the general public agree with principles of ventilator allocation developed internationally?, Study Design and Methods: A four-point Likert scale questionnaire was used to assess the extent of agreement or disagreement with internationally developed triage principles for rationing mechanical ventilators during pandemics. Questionnaires were distributed in person or online, and generalized linear models were used to analyze quantitative data. Free-text descriptions were analyzed qualitatively, both deductively and inductively, to compare respondent opinions with those described in previous US studies., Results: Of 3,191 surveys distributed, 1,520 were returned. Allocation of resources to maximize survival from current illness ("save the most lives") was the most popular triage principle, with 95.8% of respondents in agreement. Allocation to ensure a minimum duration of benefit, as determined by predicted prognosis after illness ("ensure minimum duration of benefit"), and allocation to persons who have experienced fewer life stages ("life cycle") obtained agreement of 82.2% and 80.1%, respectively. Withdrawal and reallocation of mechanical ventilators to more appropriate patients was supported by 64.4% of respondents. Only 28.4% of respondents supported the principle of first-come, first-served access to ventilators., Interpretation: Most respondents supported allocation principles developed internationally and disagreed with the idea of first-come, first-served allocation during resource shortages. The Japanese public seems largely to be prepared to discuss the ethical dilemmas and possible solutions regarding fair and transparent allocation of critical care resources as a necessary step in confronting present and future pandemics and disasters., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

In Japan, government support for human papillomavirus (HPV) vaccination began in November 2010. However, the mass media repeatedly reported on severe adverse events. The Japanese Ministry of Health, Labor and Welfare suspended proactive recommendations for HPV vaccines in June 2013. Japan's HPV vaccination rate dropped from 70% to less than 1% in 2017.We examined cervical cancer screening results in terms of abnormal cytology, histology, and HPV vaccination status among 11,903 women aged 20 to 25 y in the fiscal year 2015. The overall rate of HPV vaccination was 26.1% (3,112/11,903). Regarding cytology, the rate of atypical squamous cells of undetermined significance (ASC-US) or worse was 3.3% (103/3,112) in women who received HPV vaccination (vaccine (+) women) and 5.6% (496/8,791) in women who did not (vaccine (-) women). The rate of high-grade squamous intraepithelial lesion (HSIL) or worse was 0.26% (8/3,112) in vaccine (+) women and 0.81% (72/8,791) in vaccine (-) women. Regarding histology, the rate of cervical intraepithelial neoplasia 1 or worse (CIN1+) was 1.4% (42/3,112) in vaccine (+) women and 2.1% (178/8,791) in vaccine (-) women. The rates of CIN2+ and CIN3+ were similar regardless of vaccination. We found a significantly lower incidence of CIN in vaccine (+) women. These results suggest that the resumption of recommending HPV vaccination as primary prevention for cervical cancer is needed in Japan.

As older adults in an early stage (prefrailty) of frailty may return to a healthy state, it is necessary to examine the prevention of prefrailty. In this context, the number and types of social participation activities associated with physical prefrailty in community-dwelling older adults have remained relatively unexplored. This cross-sectional study investigates this issue by analyzing 616 participants living in Okinoshima, Shimane, a rural area of Japan, in 2019. Frailty was assessed using the 5-item frailty phenotype (unintentional weight loss, self-reported exhaustion, weakness, slow walking speed, and low physical activity). Data on social participation were obtained using a questionnaire based on participants' level of involvement with volunteer groups, sports clubs/groups, neighborhood associations, religious organizations/groups, and community elderly salons; their answers were categorized as "yes" if they answered "several times per year or more" and "no" if they answered "never." Binominal logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of prefrailty by the number or types of social participation activities, adjusted for gender, age, body mass index, smoking, medication-taking, educational attainment, working status, and living arrangement. Of the 616 participants, 273 (44.3%) and 28 (4.5%) had prefrailty and frailty, respectively. The analysis showed that the number of social participation activities was significantly associated with lower odds of prefrailty (OR = 0.83; 95% CI, 0.74-0.94). Regarding the types of social participation, sports clubs/groups were associated with lower odds of prefrailty (OR = 0.47; 95% CI, 0.31-0.73). Participation in neighborhood associations was associated with prefrailty/frailty (OR = 0.57; 95% CI, 0.37-0.86). These results suggest that increasing the number of social participation activities or involvement in sports clubs/groups and neighborhood associations may be important to prevent physical prefrailty in the older population., Competing Interests: The authors have declared that no competing interests exist.

Background: Although moderate-to-vigorous physical activity (MVPA) has multiple health benefits, current participation in recommended MVPA level and its determinants among Japanese children and adolescents remain unclear. Therefore, this cross-sectional study investigated the prevalence of meeting recommended MVPA level and its correlates among Japanese children and adolescents., Methods: Using the Japanese version of the World Health Organization (WHO) Health Behaviour in School-aged Children survey questionnaire, we confirmed the prevalence of meeting recommended MVPA level in all primary schools (PS) and junior high schools (JHS) in Unnan City, Japan. We evaluated its association with school grade, gender, body weight status, screen time, consumption of breakfast, physical activity (PA) preference, and population density using Poisson regression., Results: We found that 20.1% of the 1,794 students (9-15 years old) met the WHO recommendation. Meeting recommended MVPA level was significantly associated with being in the sixth grade of PS (prevalence ratio [PR] 0.57; 95% confidence interval [CI], 0.39-0.84) and first (PR 1.52; 95% CI, 1.16-1.99), second (PR 1.45; 95% CI, 1.10-1.90), and third grade of JHS (PR 0.40; 95% CI, 0.26-0.62) (vs fourth grade of PS); being a boy (PR 1.33; 95% CI, 1.12-1.59) (vs girl); liking PA (PR 3.72; 95% CI, 2.22-6.22) (vs dislike); and belonging to a medium-population-density (PR 0.73; 95% CI, 0.61-0.88) or low-population-density area (PR 0.67; 95% CI, 0.48-0.94) (vs high-population-density area)., Conclusions: About 20% of Japanese children and adolescents engaged in the recommended MVPA level. MVPA was associated with grade, gender, preference for PA, and population density.

Objective: To report the course of 3 recent Japanese and European cases of fingolimod-associated progressive multifocal leukoencephalopathy (PML) and to analyze its risk factors and increased incidence in Japan., Methods: Case series and literature review., Results: Fingolimod-associated PML may cause both supratentorial and infratentorial lesions and a pronounced disability. Diagnosis can be challenging because PML lesions (especially infratentorial) can be initially misdiagnosed as extensive MS lesions. Immune reconstitution inflammatory syndrome (IRIS) develops a few weeks after fingolimod discontinuation and is usually mild. Age factor and therapy duration seem to be relevant because most reported patients were older than 45 years and were treated with fingolimod for more than 3 years. Combined IgG/IgM deficiency has been identified as a possible further predisposing condition in 1 case. Another patient developed an endogenous fungal skin infection, as a sign of generally compromised cellular immune response, shortly before PML. None of the reported patients had lymphocyte counts below 200/μl. Two of the 3 reported and 4 of the 21 (19%) registered fingolimod-PML cases occurred in Japan (estimated risk of 0.652 per 1,000 compared with 0.083 per 1.000 worldwide)., Conclusions: The risk of PML under fingolimod is low, but there are no reliable predictors. Despite a mild IRIS phase, it causes profound disability. Patients older than 45 years, especially with known comorbid immunodeficiencies or manifestation of other opportunistic infections, should be monitored more closely. Increased surveillance and identification of further risk factors are urgently needed in Japan.

Importance: Few studies with sufficient statistical power have shown the association of the z score of the coronary arterial internal diameter with coronary events (CE) in patients with Kawasaki disease (KD) with coronary artery aneurysms (CAA)., Objective: To clarify the association of the z score with time-dependent CE occurrence in patients with KD with CAA., Design, Setting, and Participants: This multicenter, collaborative retrospective cohort study of 44 participating institutions included 1006 patients with KD younger than 19 years who received a coronary angiography between 1992 and 2011., Main Outcomes and Measures: The time-dependent occurrence of CE, including thrombosis, stenosis, obstruction, acute ischemic events, and coronary interventions, was analyzed for small (z score, <5), medium (z score, ≥5 to <10; actual internal diameter, <8 mm), and large (z score, ≥10 or ≥8 mm) CAA by the Kaplan-Meier method. The Cox proportional hazard regression model was used to identify risk factors for CE after adjusting for age, sex, size, morphology, number of CAA, resistance to initial intravenous immunoglobulin (IVIG) therapy, and antithrombotic medications., Results: Of 1006 patients, 714 (71%) were male, 341 (34%) received a diagnosis before age 1 year, 501 (50%) received a diagnosis between age 1 and 5 years, and 157 (16%) received a diagnosis at age 5 years or older. The 10-year event-free survival rate for CE was 100%, 94%, and 52% in men (P < .001) and 100%, 100%, and 75% in women (P < .001) for small, medium, and large CAA, respectively. The CE-free rate was 100%, 96%, and 79% in patients who were not resistant to IVIG therapy (P < .001) and 100%, 96%, and 51% in patients who were resistant to IVIG therapy (P < .001), respectively. Cox regression analysis revealed that large CAA (hazard ratio, 8.9; 95% CI, 5.1-15.4), male sex (hazard ratio, 2.8; 95% CI, 1.7-4.8), and resistance to IVIG therapy (hazard ratio, 2.2; 95% CI, 1.4-3.6) were significantly associated with CE., Conclusions and Relevance: Classification using the internal diameter z score is useful for assessing the severity of CAA in relation to the time-dependent occurrence of CE and associated factors in patients with KD. Careful management of CE is necessary for all patients with KD with CAA, especially men and IVIG-resistant patients with a large CAA.

Background: Evidence from a limited number of short-term trials indicates the difficulty in achieving population-level improvements in physical activity (PA) through community-wide interventions (CWIs). We sought to evaluate the effectiveness of a 5-year CWI for promoting PA in middle-aged and older adults using a cluster randomized design., Methods: We randomized 12 communities in Unnan, Japan, to either intervention (9) or control (3). Additionally, intervention communities were randomly allocated to three subgroups by different PA types promoted. Randomly sampled residents aged 40-79 years responded to the baseline survey (n = 4414; 74%) and were followed at 1, 3 and 5 years (78-83% response rate). The intervention was a 5-year CWI using social marketing to promote PA. The primary outcome was a change in recommended levels of PA., Results: Compared with control communities, adults achieving recommended levels of PA increased in intervention communities [adjusted change difference = 4.6 percentage points (95% confidence interval: 0.4, 8.8)]. The intervention was effective for promoting all types of recommended PAs, i.e. aerobic (walking, 6.4%), flexibility (6.1%) and muscle-strengthening activities (5.7%). However, a bundled approach, which attempted to promote all forms of PAs above simultaneously, was not effective (1.3-3.4%, P ≥ 0.138). Linear dose-response relationships between the CWI awareness and changes in PA were observed (P ≤ 0.02). Pain intensity decreased in shoulder (intervention and control) and lower back (intervention only) but there was little change difference in all musculoskeletal pain outcomes between the groups., Conclusions: The 5-year CWI using the focused social marketing strategy increased the population-level of PA.

Very few community intervention studies that promote physical activity (PA) using guidelines and its dissemination and implementation have been conducted. Consequently, we evaluated the effectiveness of a community-wide intervention (CWI) of PA with adults based on the Japanese guidelines for promoting PA. This was a non-randomized controlled trial, with four administrative districts in Fujisawa city assigned to the intervention group and nine to the control group. The CWI, conducted from 2013 to 2015, comprised information dissemination, education, and community support. The primary outcome was change in PA participation. Secondary outcomes were CWI awareness and PA guideline knowledge. Outcomes were assessed using questionnaires distributed to two independent, random samples of 3000 community-based adults (aged ≥20years). Two separate samples-1230 adults at baseline and 1393 at the two-year follow-up-responded to the survey. The median time spent in PA did not differ between intervention and control groups after adjusting for potential confounders (adjusted difference between groups=-0.02min/day [95% confidence interval (CI): -0.11, 0.10]). However, intervention group participants were more aware of the CWI (33.8%) than were control group participants (25.2%) at the two-year follow-up (odds ratio=1.44 [95% CI: 1.06, 1.95]). A significant difference was also observed in participants' PA guideline knowledge (adjusted difference between groups=0.82% [95% CI: 0.33, 1.31]). Although significant differences in awareness and knowledge were observed between groups, this CWI did not change PA levels over two years. Future studies should investigate the long-term effects of CWIs beyond two years., Trial Registration Number: UMIN-CTR UMIN000018389., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Mutations in REEP1 have been identified in three types of neurological disorders, autosomal dominant form of Hereditary Spastic Paraplegia type 31 (SPG31), autosomal dominant distal hereditary motor neuronopathy type VB (HMN5B), and autosomal recessive form of congenital axonal neuropathy and diaphragmatic palsy. Previous studies demonstrated different molecular pathogenesis in SPG31, including loss-of-function, gain-of-function and haploinsufficiency. A four-generation family from Japan, including 12 members, was investigated clinically and genetically. Seven affected members displayed pure spastic paraplegia. Impression of genetic anticipation was observed in the family, including tendency of earlier age-at-onset and increasing severity in subsequent generations. Genetic analysis revealed a heterozygous intronic variant, c.303+2T > A, in REEP1, which segregated with disease, and was also identified in one unaffected member. The variant causes exon 4 skipping leading to frame shift and a truncated transcript identified by complementary DNA sequencing of reverse transcription polymerase chain reaction products. Measurement of REEP1 transcripts in lymphocytes demonstrated a reduction through nonsense mediated mRNA decay (NMD). Our study demonstrated further evidence of allelic heterogeneity in SPG31, mutant REEP1 mRNA dosage effects through NMD and intra-familial phenotype variability., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: We investigated possible genotype-phenotype correlations in Japanese patients with familial amyotrophic lateral sclerosis (FALS) carrying fused in sarcoma/translated in liposarcoma (FUS/TLS) gene mutations., Methods: A consecutive series of 111 Japanese FALS pedigrees were screened for copper/zinc superoxide dismutase 1 (SOD1) and FUS/TLS gene mutations. Clinical data, including onset age, onset site, disease duration, and extramotor symptoms, were collected., Results: Nine different FUS/TLS mutations were found in 12 pedigrees. Most of the patients with FUS/TLS-linked FALS demonstrated early onset in the brainstem/upper cervical region, and relatively short disease duration. A few mutations exhibited phenotypes that were distinct from typical cases. Frontotemporal dementia was present in 1 patient., Conclusions: This study revealed a characteristic phenotype in FUS/TLS-linked FALS patients in Japan. FUS/TLS screening is recommended in patients with FALS with this phenotype. Muscle Nerve 54: 398-404, 2016., (© 2016 Wiley Periodicals, Inc.)

Background: In Japan, the incidence of kidney stones has increased markedly in recent decades. Major causes of kidney stones remain unclear, and limited data are available on the relationship between overweight/obesity and the incidence of kidney stones. We therefore evaluated body mass index (BMI) and the incidence of kidney stones in Japanese men., Methods: Of the workers at a gas company, 5984 males aged 20-40 years underwent a medical examination in 1985 (baseline). This study includes 4074 of the men, who were free of kidney stones at baseline and underwent a second medical examination performed between April 2004 and March 2005. BMI was calculated from measured height and weight in 1985, and men were categorized into tertiles. The development of kidney stones during follow-up was based on self-reports from questionnaires at the second medical examination., Results: The average duration of follow-up was 19 years, with 258 participants developing kidney stones during this period. Using the lowest BMI (1st tertile) group as a reference, the hazard ratios (95% confidence intervals [CIs]) for the 2nd and 3rd BMI tertiles were: 1.26 (95% CI, 0.92-1.73) and 1.44 (95% CI, 1.06-1.96), respectively (P for trend = 0.019). After additionally adjusting for potential confounders, such as age, systolic blood pressure, cardiorespiratory fitness, cigarette smoking, and alcohol consumption, the hazard ratios were 1.28 (95% CI, 0.93-1.76) and 1.41 (95% CI, 1.02-1.97), respectively (P for trend = 0.041)., Conclusions: These results suggest that increased BMI is a risk factor for kidney stones in Japanese men.

Background: Promotion of physical activity (PA) is a key strategy to prevent non-communicable diseases. However, evidence on the effectiveness of community-wide interventions (CWIs) for promoting PA is limited., Purpose: To evaluate the effectiveness of a 3-year CWI for promoting PA in middle-aged and older adults compared with usual public health services. This study is an extension to an original 1-year investigation study., Design: Cluster randomized controlled trial with community as unit of randomization and individual as unit of analysis., Setting/participants: 12 communities in Unnan, Japan were randomly allocated to the intervention (9) or the control (3). Additionally intervention communities were randomly allocated to aerobic activity promotion (Group A), flexibility and muscle-strengthening activities promotion (Group FM), or aerobic, flexibility, and muscle-strengthening activities promotion (Group AFM), each consisting of three communities. Randomly-sampled 4414 residents aged 40 to 79 years responded to the baseline survey (74%), and were analyzed in 2013-2014., Intervention: A 3-year CWI based on social marketing, to promote PA from 2009 to 2012., Main Outcome Measures: The primary outcome was a change in regular aerobic, flexibility, and/or muscle-strengthening activities, defined by (1) engaging in 150 mins/week or more of walking, (2) engaging in daily flexibility activity, or (3) engaging 2 or more days/week in muscle-strengthening activities, evaluated at the individual level. Secondary outcomes were changes in specific types of PA and musculoskeletal pain. Outcomes were measured at baseline and at 1 and 3 years (2009, 2010, and 2012)., Results: The CWI did not significantly increase the proportion of adults who reached recommended levels of aerobic, flexibility, and/or muscle-strengthening activities (adjusted change difference = 1.6% [95% CI: -3.5, 6.6]). In the subgroup analysis, compared to the controls, adults doing flexibility activity daily significantly increased in Group FM (6.3% [95% CI: 1.9, 10.7]). In Group A and AFM for PA outcomes and in all groups for pain outcomes, there was no significant change compared to controls., Conclusions: The CWI did not achieve significant increase in the proportion of adults who reached recommended PA levels. However, it might be effective in promoting flexibility activity in middle-aged and older Japanese., Trial Registration: UMIN-CTR UMIN000002683 .

Aim: The present study examined whether low back pain (LBP) and knee pain (KP) are associated with trips and falls in rural Japanese community-dwelling older adults., Methods: A population-based cross-sectional survey of community-dwelling older adults was carried out in Unnan City, Shimane Prefecture, in Japan. A total of 499 men and women aged 60 years and older living in the community were recruited from 2008 to 2010. The main outcome measures were self-rated recent trip frequency and self-reported experience of falls in the past year., Results: Trips and falls presented in 44.0% and 15.9% of participants, respectively. LBP was not associated with trips, but was significantly associated with falls: severe pain versus single fall (odds ratio [OR] 2.51, 95% confidence interval [CI] 1.04-6.03); and severe pain versus multiple falls (OR 11.09, 95% CI 2.41-51.10). KP was significantly associated with trips: mild pain versus trips (OR 1.81, 95% CI 1.20-2.72); mild pain versus multiple falls (OR 4.47, 95% CI 1.21-16.50); severe pain versus trips (OR 3.83, 95% CI 1.82-8.04); and severe pain versus multiple falls (OR 7.26, 95% CI 1.51-34.86). Participants with both pain sites were associated with trips (OR 2.44, 95% CI 1.45-4.12) and multiple falls (OR 10.79, 95% CI 1.33-87.19)., Conclusions: Severe LBP was associated with single and multiple falls, whereas KP was associated with trips and multiple falls, irrespective of severity of pain. In addition, participants with both pain types were associated with trips and multiple falls., (© 2014 Japan Geriatrics Society.)

It is known that overweight is associated with chronic knee pain (CKP) and chronic low back pain (CLBP). Several risk factors for these conditions have been postulated, including age, sex, overweight, occupation, and socioeconomic factors. In addition, physical environment has been studied as a potential risk factor in recent years. However, the associations of overweight and physical environment with CKP and CLBP remains unclear. The aim of this study conducted in a rural mountainous region was to examine whether overweight individuals living at higher elevations have an increased probability of experiencing CKP and CLBP. In 2009, we conducted a mail survey with a random sample aged between 40 to 79 years. Questionnaires were sent to 6,000 individuals and a total of 4,559 individuals responded to this survey. After excluding the respondents with missing data, we conducted a logistic regression analysis of the data for 3,109 individuals. There was statistically significantly higher adjusted odds ratio (aOR) of CKP for those who were overweight living at low elevation (aOR = 1.90, 95% CI = 1.21-2.98), moderate elevation (aOR = 1.73, 95% CI = 1.05-2.87), and high elevation (aOR = 2.13, 95% CI = 1.31-3.46) than those who were not overweight living at low elevation. However, similar patterns were not observed for CLBP. Our results show that specific overweight-elevation associations were observed for CKP in a rural mountainous region.

Background: Both little and excessive physical activity (PA) may relate to chronic musculoskeletal pain. The primary objective of this study was to characterize the relationship of PA levels with chronic low back pain (CLBP) and chronic knee pain (CKP)., Methods: We evaluated 4559 adults aged 40-79 years in a community-based cross-sectional survey conducted in 2009 in Shimane, Japan. We used self-administered questionnaires to assess sociodemographics and health status: PA was assessed by the International Physical Activity Questionnaire, and CLBP and CKP were assessed by a modified version of the Knee Pain Screening Tool. We examined relationships of PA with prevalence of CLBP and CKP using Poisson regression, controlling for potential confounders., Results: CLBP and CKP were both prevalent (14.1% and 10.7%, respectively) and associated with history of injury, medication use, and consultation with physicians. PA was not significantly related to CLBP or CKP (P > 0.05) before or after adjustment for potential confounders. For example, compared with adults reporting moderate PA (8.25-23.0 MET-hours/week), prevalence ratios for CKP adjusted for sex, age, education years, self-rated health, depressive symptom, smoking, chronic disease history, and body-mass index were 1.12 (95% confidential interval [CI] 0.84-1.50) among those with the lowest PA and 1.26 (95% CI 0.93-1.70) among those with the highest PA (P quadratic = 0.08). The prevalence ratios were further attenuated toward the null after additional adjustment for history of injury, medication use, and consultation (P quadratic = 0.17)., Conclusions: This cross-sectional study showed that there were no significant linear or quadratic relationships of self-reported PA with CLBP and CKP. Future longitudinal study with objective measurements is needed.

Background: We aimed to evaluate the effectiveness of a community-wide campaign (CWC) for promoting physical activity in middle-aged and elderly people., Methods: A cluster randomized controlled trial (RCT) with a community as the unit of randomization was performed using a population-based random-sampled evaluation by self-administered questionnaires in the city of Unnan, Shimane Prefecture, Japan. The evaluation sample included 6000 residents aged 40 to 79 years. We randomly allocated nine communities to the intervention group and three to the control group. The intervention was a CWC from 2009 to 2010 to promote physical activity, and it comprised information, education, and support delivery. The primary outcome was a change in engaging in regular aerobic, flexibility, and/or muscle-strengthening activities evaluated at the individual level., Results: In total, 4414 residents aged 40-79 years responded to a self-administered questionnaire (73.6% response rate). Awareness of the CWC was 79% in the intervention group. Awareness and knowledge were significantly different between the intervention and control groups, although there were no significant differences in belief and intention. The 1-year CWC did not significantly promote the recommended level of physical activity (adjusted odds ratio: 0.97; 95% confidence interval: 0.84-1.14)., Conclusions: This cluster RCT showed that the CWC did not promote physical activity in 1 year. Significant differences were observed in awareness and knowledge between intervention and control groups as short-term impacts of the campaign., Trial Registration: UMIN-CTR UMIN000002683.

Background/aims: To compare the perinatal outcomes after laparoscopic myomectomy (LM) versus abdominal myomectomy (AM)., Methods: The medical records of 105 Japanese females who delivered after myomectomy from 2004 to 2012 at Osaka Medical College were reviewed retrospectively., Results: Of the 105 females who delivered after myomectomy, 48 had undergone LM and 57 had undergone AM. There were no significant differences in the perinatal outcomes including the rates of emergency cesarean sections, preterm deliveries, placental abnormalities, pregnancy-induced hypertension, low Apgar score, non-reassuring fetal heart rate patterns, and intrauterine fetal death. No significant difference was observed in the incidence of post-partum hemorrhage. There was no uterine rupture in either group. 15 (31%) of the females who had LM were candidates for transvaginal delivery, and 14 delivered vaginally (93% success rate). In contrast, 20 (35%) of the females who had AM were candidates for transvaginal delivery, and 19 delivered vaginally (95% success rate)., Conclusion: There were no significant differences in the perinatal outcomes between the females who had LM and AM. Moreover, both groups had a high rate of successful transvaginal delivery after selecting the appropriate candidates., (© 2013 S. Karger AG, Basel.)

Purpose: To understand the current clinical features of kidney cancers in patients with von Hippel-Lindau (VHL) disease in Japan., Subject and Result: We performed a nationwide epidemiological survey of patients with VHL disease using the epidemiology program for incurable disease by the Ministry of Health, Labour and Welfare. The content of the survey included age of onset of VHL disease, sex, residential area, treatment modalities, kidney function, ECOG performance status, and prognosis. Here, we report the results of kidney cancer. The incidence rate of kidney cancer in VHL disease in Japan is 50.3% (206/409). Males and females are equally affected. The mean age of onset is 37.8 + 0.92 years. The median age of onset is 35 years. The ages of onset are distributed between 15 and 75 years. The mostly affected age of onset is between 20 and 50 years. The incidence rate of patients with metastasis is 11.1% (23/206). The most common site for metastasis is the lung (60%, 14/23). Due to multiple numbers of tumors at initial diagnosis and the metachronous development of tumors, patients received treatment on multiple occasions (mean 1.6 times), including partial nephrectomy (46%), total nephrectomy (31%) or radiofrequency ablation (14%) up to 6 times. The multiple treatments resulted in deterioration of the kidney function, causing chronic dialyses in 7 cases (3%). The ECOG performance status was scored as more than 1 in 42% of patients. The ten-year survival rate in VHL patients with kidney cancer was 94%, which is relatively high compared with that survival rates in sporadic kidney cancers., Conclusion: The current study indicates that the age of onset of kidney cancers in VHL disease is relatively young, and kidney cancers have features of metachronous development. The clinical features of kidney cancer developed in VHL disease among Japanese population are very similar with those in European countries. Multiple treatments result in deterioration of the kidney function.

Gynecology in the office setting is developing worldwide. Clinical guidelines for office gynecology were first published by the Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists in 2011. These guidelines include a total of 72 clinical questions covering four areas (Infectious disease, Malignancies and benign tumors, Endocrinology and infertility, and Healthcare for women). These clinical questions were followed by several answers, backgrounds, explanations and references covering common problems and questions encountered in office gynecology. Each answer with a recommendation level of A, B or C has been prepared based principally on evidence or consensus among Japanese gynecologists.These guidelines would promote a better understanding of the current standard care practices for gynecologic outpatients in Japan., (© 2012 The Authors; Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.)

Contagious equine metritis (CEM), a contagious venereal disease of horses, invaded Japan in 1980 and spread in the Thoroughbred population of the Hidaka-Iburi district of Hokkaido. To eradicate CEM, we ran a program aimed at detecting Taylorella equigenitalis, the causal agent, in carrier horses by using the PCR test, followed by culling or treatment. In 2001, the first year of the program, 12,356 Thoroughbred racing stallions and mares were tested and 11 carriers were found. Four, two, one, and one carrier mares were detected in 2002, 2003, 2004, and 2005, respectively, by application of the program at the same scale as in 2001. No PCR-positive horses were found from 2006 to 2010. These results strongly suggest that CEM was eradicated from Japan by 2010.

We investigated the genetic structure of populations of the brackish-water crab Deiratonotus cristatus (de Man, 1895) (family Camptandriidae) on the Japanese coast, together with morphological and the ecological variations. Genetic characteristics of the local populations based on mitochondrial DNA COI sequence data have revealed genetic differentiation between many populations, with the haplotype networks forming three geographical clades: a clade occurring on the Pacific coast, one occurring predominantly in northern Hokkaido, Kyushu and the Seto Inland Sea, and a third occurring in the Ryukyu Islands. Male pleopod morphology, carapace length relative to carapace width, and carapace width of adult crabs varied inconsistently among the geographic groups corresponding to the three clades. Life history traits were similar throughout, although differences in the breeding season were apparent between populations on the Pacific coast, and in the Seto Inland Sea and the Ryukyu Islands.

Mutations in the optineurin (OPTN) gene cause amyotrophic lateral sclerosis (ALS). We previously reported 3 types of OPTN mutation in Japanese ALS subjects. Here, to identify the OPTN mutations in individuals of different ethnicity, we screened 563 sporadic ALS (SALS) subjects and 124 familial ALS (FALS) subjects who were mainly Caucasian. We found a c.964T>C synonymous variation in exon 8. However, we could not find the meaningful OPTN mutations. The results indicate that OPTN mutations causing ALS are rare, especially in mainly Caucasian ALS subjects., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Physical activity contributes to maintaining functional ability later in life. Specific relationships between walking for particular purposes (eg, recreation or transport) and functional ability are not clear. It is useful for planning health promotion strategies to clarify whether walking time for recreation, or walking time for transport has the stronger relationship with maximum walking speed (MWS), a determinant of functional ability later in life in the elderly., Methods: A cross-sectional survey was conducted in 2007 using a sample of 372 community-dwelling elderly people aged 60 to 87 years in Mitoya Town, Unnan City, rural Japan. Associations with MWS were examined for self-reported weekly times of walking for recreation and for transport using multiple linear regression analyses., Results: Both in men and women, walking time for recreation was significantly associated with MWS after controlling for age, height, weight, hip and knee pain, and a number of chronic diseases (men: β = 0.18, P = .024; women: β = 0.17, P < .01). However, walking time for transport was not significantly associated with MWS (men: β = -0.094, P = .24; women: β = -0.040, P = .50)., Conclusions: Walking for recreation may contribute to maintaining functional abilities such as MWS in the elderly.

Background: Although previous studies have reported physical activity and its sociodemographic determinants using self-report measures, there have been few studies using pedometers., Purpose: To ascertain pedometer-determined physical activity and its sociodemographic determinants among community residents living in four Japanese cities., Methods: A cross-sectional mail survey was conducted from February 2007 to January 2008 with a sample of 4000 residents (aged 20-69 years and 50% male) who were randomly selected from the registry of residential addresses. Complete responses for both questionnaire and pedometer were obtained from 790 residents (48.3±13.7 years, 46.7% male). Associations of 11 sociodemographic variables with steps per day were examined using multiple logistic regression analyses. Data were analyzed in 2010., Results: Men averaged 8763±3497 steps/day and women averaged 8242±3277 steps/day. Further, 29.0% of men and 27.8% of women walked ≥10,000 steps/day. City of residence, good self-rated health, low educational attainment, and not owning a car were associated with taking ≥10,000 steps/day in men, whereas employed status and dog ownership were associated with walking ≥10,000 steps/day in women., Conclusions: The results contribute to understanding of step-defined physical activity and its sociodemographic determinants. A diversity of step counts by sociodemographic variables clarifies specific populations among Japanese who are in need of intervention to promote physical activity., (Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Amyotrophic lateral sclerosis (ALS) has its onset in middle age and is a progressive disorder characterized by degeneration of motor neurons of the primary motor cortex, brainstem and spinal cord. Most cases of ALS are sporadic, but about 10% are familial. Genes known to cause classic familial ALS (FALS) are superoxide dismutase 1 (SOD1), ANG encoding angiogenin, TARDP encoding transactive response (TAR) DNA-binding protein TDP-43 (ref. 4) and fused in sarcoma/translated in liposarcoma (FUS, also known as TLS). However, these genetic defects occur in only about 20-30% of cases of FALS, and most genes causing FALS are unknown. Here we show that there are mutations in the gene encoding optineurin (OPTN), earlier reported to be a causative gene of primary open-angle glaucoma (POAG), in patients with ALS. We found three types of mutation of OPTN: a homozygous deletion of exon 5, a homozygous Q398X nonsense mutation and a heterozygous E478G missense mutation within its ubiquitin-binding domain. Analysis of cell transfection showed that the nonsense and missense mutations of OPTN abolished the inhibition of activation of nuclear factor kappa B (NF-kappaB), and the E478G mutation revealed a cytoplasmic distribution different from that of the wild type or a POAG mutation. A case with the E478G mutation showed OPTN-immunoreactive cytoplasmic inclusions. Furthermore, TDP-43- or SOD1-positive inclusions of sporadic and SOD1 cases of ALS were also noticeably immunolabelled by anti-OPTN antibodies. Our findings strongly suggest that OPTN is involved in the pathogenesis of ALS. They also indicate that NF-kappaB inhibitors could be used to treat ALS and that transgenic mice bearing various mutations of OPTN will be relevant in developing new drugs for this disorder.

Objective: This study examined the relationship between physical activity and the environment among rural Japanese women, and whether that relationship varied with driving status., Methods: 434 women aged 40-64 years in Unnan City, rural Japan, were surveyed in 2006 about physical activity and their neighborhood environments. The proximity and frequency of public transport were measured using geographic information systems software., Results: Perceived good access to public transport and recreational facilities, presence of bike lanes, and good aesthetics were among factors positively associated with being physically active. The interaction between the convenience of bus service and driving status was statistically significant (P=0.023). Non-drivers residing in areas where bus service was moderately convenient were more likely to be active than those who were without it., Conclusion: These findings suggested that driving status is a potential modifier of the relationship between physical activity and the convenience of bus service and that convenient bus service is important for promoting physical activity especially in non-drivers.

Background: Physical activity is known to prevent obesity and metabolic syndrome in middle-aged and elderly people; however, the effectiveness of a comprehensive health education program for male white-collar employees is uncertain., Methods: Forty-three men volunteered to participate in this study and were randomly assigned into 2 groups. The intervention group participated in a 2-hour program comprising comprehensive health education and hot spa bathing, offered once every 2 weeks, in addition to individualized programs once a week, for 24 weeks. The control group received only general health guidance. We compared their lifestyle characteristics and physical and mental health criteria at baseline, immediately after the intervention, and 1 year after the end of the intervention., Results: Rates of adherence to individualized programs were 60.0 +/- 27.2% and 30.5 +/- 29.6% at the end of the intervention and at 1 year after the end of the intervention, respectively. Significant (P < 0.05) interaction of criteria was observed for cluster of differentiation 4+ (CD4+) cells and the ratio of cluster of differentiation 4+ to 8+ (CD4/8) cells, which were used to represent the participants' immunological function. We divided the intervention group into 2 subgroups on the basis of their attendance. Among the resulting 3 groups, significant interaction of criteria was observed for CD4+ and CD4/8 cells. In addition, the high attendance group had the highest CD4+ count and CD4/8 ratio., Conclusions: Participants who attended classes and/or performed the supplementary individualized programs tended to maintain their immunological function and to experience a decrease in body fat percentage. However, few effects were noted in participants with poor adherence, even in the intervention group.

To compare the incidence of aseptic meningitis associated with symptomatic natural mumps infection and in mumps vaccine recipients, we conducted a prospective comparative study. Consecutive samples of 1051 children with mumps were enrolled by 10 pediatricians and 21,465 vaccine recipients by 143 pediatric primary care practitioners, from January 1, 2000 to January 1, 2003. Parents used a daily diary to record symptoms during the period of illness (15 days) or 30-day period following immunization. Mumps infection was confirmed by virus isolation and/or detection of mumps virus genome in salivary and CSF samples. The incidence of aseptic meningitis was 13/1051 (1.24%) in patients with symptomatic natural mumps infection and was estimated to be 0.7-1.1% of overall infection in considering asymptomatic infection, and 10/21,465 (0.05%) in vaccine recipients. Although aseptic meningitis is a clear side effect of the mumps vaccine, the incidence is considerably lower than among those with symptomatic natural infection. Our results provide an informative data for consideration to resume mumps vaccine as a part of routine immunization schedule for Japanese children.

During the 2000/2001 influenza season in Japan, children ranging in age from 6 months to 13 years with fever exceeding 37.5 degrees C were recruited. Vaccine efficacy was evaluated by comparing the rates of pre-seasonal vaccination between groups stratified by fever severity. Seven hundred and sixty one patients (33.1%), culture positive for influenza were enrolled for analysis. The numbers of patients for A/H1N1 and A/H3N2 were insufficient for statistical analysis. For influenza B the odds ratio for vaccinated children to have a maximum fever exceeding 39.5 degrees C was 0.52 (95% CI, 0.30-0.92) Our findings suggest modest impact of influenza vaccination on limiting severity of disease symptoms.

To search for additional amplification and deletion sites that may serve as a starting point for the discovery of new oncogenes or tumor suppressor genes, 30 Japanese localized prostate cancers were analyzed by comparative genomic hybridization (CGH) in this study. CGH was used to search for changes in DNA sequence copy-number in a series of 30 primary prostate adenocarcinomas, consisting of 22 cases of pT2N0 (organ confined; without capsular invasion) and 8 cases of pT3N0 (with capsular invasion), removed by radical prostatectomy. CGH revealed that the shortest regions of overlap (SRO) of gains in pT2N0 were at 8q22.2 approximately q24.2, 11q13.1 approximately q14.1, and 12q23 approximately q24.2, whereas the SRO of losses were seen at 8p23.3 approximately p22, 13q21.2 approximately p22, and 18q21 approximately q22. The SRO of gains in pT3N0 were noted at 5q32 approximately q34, 8q22.3 approximately q24.1, 11q14.1 approximately q22.3, and 12q22 approximately q24.2, whereas the SRO of losses were seen at 18q21.2 approximately q23. These results suggest that gains or losses of DNA in these regions are important for prostate cancer progression. The detection of the SRO may serve as a starting point to discover novel oncogenes and tumor suppressor genes involved in prostate cancer progression.

Declining incentives and scholastic abilities in science class has been concerned in Japan. The Ministry of Education, Culture, Sports, Science and Technology encourages schools to cooperate with research institutions to raise student's interest in natural sciences. The Science Partnership Program (SPP) and the Super Science High-School (SSH) are among such efforts. Our short SPP course consists of an introductory lecture on space biology in general and a brief laboratory practice on plant gravitropism. Space biology class is popular to students, despite of the absence of flight experiments. We suppose that students are delighted when they find that their own knowledge is not a mere theory, but has very practical applications. Space biology is suitable in science class, since it synthesizes mathematics, physics, chemistry and many other subjects that students might think uninteresting.

We isolated 872 strains of mumps virus from naso-pharyngeal secretions in seven different districts of Japan from January 2000 to July 2001. Among them, 57 strains were geno-typed by nucleotide sequencing in part of the hemagglutinin-neuraminidase (HN) and small hydrophobic (SH) protein regions. Four different genotypes (B, G, K, and L) of mumps virus were co-circulating in Japan and the distribution of genotypes varied in geographically different districts. Two new clusters designated as genotypes K and L had more than 7% nucleotide variation in the SH gene. Among the 57 strains, 11 were classified as B, 35 as G, three as K, and eight as L, which was mainly isolated in Tokyo. We also examined 104 stains isolated in a clinic in Mie prefecture from 1993 to 2003. Genotype B was the indigenous strain and genotype K was introduced in 1994. Genotypes B and K co-circulated in the 1990s and were replaced by genotype G in 2000. There was no significant change in neutralizing test antibody titers against genotypes B, G, K, and L using seven post-vaccination sera with Hoshino strain (genotype B) and these four genotypes had a different antigenicity from genotype A. We should continue to watch on mumps virus molecular epidemiology., (Copyright 2004 Wiley-Liss, Inc.)

We used fluorescence in situ hybridization with centromere-specific probes for chromosomes 7, 8, 10, and Y to determine the copy number of these chromosomes in metastatic prostate cancers of five Japanese cases. Freshly prepared samples were obtained from prostate needle biopsies at different phases of clinical treatment; pretreatment, 1 week, 4 weeks, 12 weeks, 24 weeks post-treatment (PT), and clinical relapse. Gain of chromosomes 7 and 8, as noted in pretreatment samples; however, in post-treatment specimens (four of five cases), a remarkable reduction in the number of cells with extra copies of these chromosomes was detected. This decrease in the number of cells with additional chromosome 7 and 8 signals was correlated with the clinicohistopathological findings until 4 weeks PT. Chromosomes Y and 10 did not show numerical aberrations before treatment or changes in cells with aneusomy after treatment in all five cases. Our results suggest that gains of chromosomes 7 and 8 correlate with high grade and stage, and that changes in the cell number with aneusomy of chromosomes 7 and 8 reflect the clinical effects of anti-androgen therapy at an early phase, which may also indicate the androgen dependency of prostate cancer cells.

To investigate the emergence of rifampin resistance in Rhodococcus equi strains isolated from foals and their environment in Japan, we compared the in vitro antimicrobial susceptibilities to rifampin of 640 isolates from 64 infected foals and 98 soil isolates from their horse-breeding farms. As a control, 39 human isolates from patients with and without AIDS were also tested for susceptibility to rifampin. All of the isolates showed rifampin sensitivity, except isolates from one infected foal and two patients with AIDS that showed rifampin resistance. To investigate the emergence of rifampin-resistant R. equi in the infected foal, which had received rifampin monotherapy for a month before euthanasia, 99 isolates of R. equi from the lesions and 20 isolates from the intestinal contents of the one foal with rifampin-resistant organisms were analyzed for rifampin susceptibilities, pathogenicities, and ribotypes. Of the 99 isolates from the lesions, all of which were virulent R. equi strains containing a virulence plasmid with a size of 85 or 90 kb, 90 (91%) isolates were rifampin resistant (MIC, > or = 12.5 microg/ml). On the other hand, of the 20 isolates from the intestinal contents, 11 (55%) isolates showed rifampin resistance (MIC, > or = 25 microg/ml), and 5 of them were avirulent R. equi strains. Among these 101 rifampin-resistant R. equi isolates with and without virulence plasmids characterized by ribotyping, 58 were type I, 20 were type II, 11 were type III, and 12 were type IV. These results demonstrated that at least eight different rifampin-resistant R. equi strains emerged concurrently and respectively from the different lesions and intestinal contents of the infected foal.

Profiles of the genomic DNA of 104 strains of T. equigenitalis isolated from brood mares with contagious equine metritis in Hokkaido during the breeding seasons from 1980 to 1993, as well as those of five strains (SS28, EQ56, EQ59, EQ70 and HH139) previously isolated in Japan were examined after restriction digestion and crossed-field gel electrophoresis. These profiles were essentially identical to each other and the various isolates and strains appeared to have a common genotype, designated 'genotype J', with respect to two restriction enzymes, ApaI and NotI. These results suggest a common source for all these isolates obtained over the course of more than 10 years in Japan.

To investigate the overall prevalence of chlamydial infections in light (i.e. non-draught) horses in Japan, 599 sera obtained from 12 localities in 1991 were tested for complement fixation antibodies. The mean antibody positive rates of the all sera were 15.2% (91/599) and the regional positive rates were higher in Honshu (19.1%, 48/251) and Kyushu (20.0%, 20/100) than in Hokkaido (9.3%, 23/248). In Honshu, the highest rate (56.0%, 28/50) was observed in Utsunomiya. Analysis of the positive rate in different age groups showed that the 2-5 years age-group had the highest prevalence of chlamydial infections. This indicates that chlamydial infection is prevalent in light horses in Japan.

Electropherotypes (ET), serotypes, and subgroups of equine rotaviruses isolated from foals in Japan were determined. The ETs of 136 isolates from 1981 through to 1991 were divided into six groups: ET-A-ET-F. The ET-A, -B, -C, -D, -E, and -F were present in 3, 1, 121, 9, 1, and 1 strains, respectively. Representative viruses of ET-A, -B, -C, and -D were identified as serotype G3. Viruses of ET-E and -F were identified as serotypes G 10 and G 5, respectively. The four representative viruses of serotype G 3 did not belong to either subgroup I or II. The two viruses of serotypes G 5 and G 10 belonged to subgroup I. Serotype G 3 strains possessing ET-C were prevalent among the foals throughout the study period.

The dissemination of equine herpesvirus types 1 (EHV-1) and 4 (EHV-4) among various horse populations in Japan was investigated through the isolation and typing of virus strains from horses with respiratory diseases. Type specific monoclonal antibody pools were used for the typing of isolates. The 42 strains of EHV-1 and 64 strains of EHV-4 were isolated from 4593 nasal swabs and/or blood plasma samples collected from 3326 horses during a period from 1979 to 1990. All the strains of EHV-1 were isolated from racehorses only and during the winter season exclusively, when the epizootic of respiratory diseases occurred among racehorse populations at two Training Centers of the Japan Racing Association. In contrast, the strains of EHV-4 were isolated from horses irrespective of the season, facility, or horse population; foals and yearlings in breeding farms and our institute, rearing horses in rearing farms, and racehorses. Especially, 4 strains of EHV-4 were isolated from plasma samples containing buffy coat cells. We believe this is the first reported case of EHV-4 cell-associated viremia in the world. All 87 strains isolated from aborted fetuses were identified as EHV-1. The results suggest that EHV-1 is responsible for epizootic respiratory diseases in racehorses in the winter and abortion among mares at the late stage of gestation, and that EHV-4 causes respiratory diseases throughout the year among all horse populations.

The prevalence of virulent Rhodococcus equi in isolates from soil and feces of foals on a farm with endemic R. equi infections was significantly higher than that of a farm with no history of the disease. Foals bred on a farm with the endemic disease might be constantly exposed to virulent R. equi in their environment.

To elucidate the current status of foal diseases in Japan, clinico-pathological analysis was conducted on 237 foal autopsy cases. As a result, bacterial infection was identified as an important cause of foal death. Most of the bacteria isolated from these cases were ubiquitous, opportunistic, environmental organisms, known to be non-pathogenic to mature animals. Most of cases with bacterial infection were diagnosed as having hypogammaglobulinemia, i.e., failure of passive transfer. In addition, the mean weight of thymuses in foals affected by bacterial infection tended to be lower than that of foals without infection. These findings suggest that the common cause of foal diseases were mainly due to the opportunistic bacterial infections associated with the weakened immune function, serving as precursor to or promotor of infection.

A primary enzootic of equine Getah virus infection involving 722 of 1,903 racehorses occurred at a training center in Japan between September and November of 1978. Sixty-two viral agents were isolated from the plasma of 209 sick horses which exhibited pyrexia with rectal temperatures ranging from 38.5--40 degrees C, urticarial rash on various portions of the body, and edema of the hind legs. The viruses were antigenically related to the AMM 2021, Haruna, and Sagiyama strains of Getah virus. Infection and disease were produced experimentally in horses when inoculated by the intramuscular or intranasal routes.