研究者詳細 - 武林　亨

論文 - 武林　亨

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Association between visual classification of kyphosis and future ADL decline in community-dwelling elderly people: the Kurabuchi study

Sugai K., Michikawa T., Takebayashi T., Matsumoto M., Nakamura M., Nishiwaki Y.

Archives of Osteoporosis （Archives of Osteoporosis） 14 （ 1 ） 2019年12月

ISSN 18623522

© 2018, The Author(s). Summary: This cohort study conducted in Japan showed that severe age-related kyphosis was visually detected. The visual assessment of kyphosis was associated with declines in ADL, suggesting that we can easily identify people at high risk to develop future ADL reduction in the community setting. Purpose: Age-related kyphosis is related with declines in activities of daily living (ADL). Its conventional diagnosis has been made by orthopedic surgeons and trained examiners using specialized equipment such as X-rays. We investigated whether visual classification of kyphosis by laypersons accurately predicted future ADL decline. Methods: This study was part of the Kurabuchi Study, a cohort study of community-dwelling elderly Japanese. Between 2009 and 2010, three layperson raters used reference illustrations to classify 532 participants without ADL decline at study baseline into four categories. Other examiners used conventional methods to assess kyphosis in the same participants: curve ruler, Spinal Mouse, and the block method. ADL decline was defined as the development of dependence according to the Katz Index, admission to a nursing home, or certification of long-term care need. Results: Thirty-five of the participants (6.6%) were classified with the most severe degree of kyphosis at baseline by visual assessment. Interrater agreement was high (Kappa = 0.73) for the most severe group. During 4.5 years of follow-up, 106 participants (19.9%) showed ADL decline. On the basis of visual assessment, the adjusted risk ratio for ADL decline among the participants with the most severe kyphosis was 2.6 (95% CI: 1.4–4.6). Assessments of kyphosis made with the Spinal Mouse also accurately predicted ADL decline. Conclusions: Visual assessment of kyphosis predicted future declines in ADL in this study. Since our method requires no special tools or training, it may be useful for identifying those at high risk of ADL decline.

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Association of blood pressure with estimates of 24-h urinary sodium and potassium excretion from repeated single-spot urine samples

Thi Minh Nguyen T., Miura K., Tanaka-Mizuno S., Tanaka T., Nakamura Y., Fujiyoshi A., Kadota A., Tamaki J., Takebayashi T., Okamura T., Ueshima H.

Hypertension Research （Hypertension Research） 42 （ 3 ） 411 - 418 2019年03月

ISSN 09169636

© 2018, The Japanese Society of Hypertension. While the association between 24-h urinary sodium and potassium excretion with blood pressure is well established, the relationships of these ions to spot urine measurements are unclear. Our purpose is to assess the association between blood pressure and the estimated 24-h sodium and potassium excretion from repeated single-spot urine samples. Spot urine and blood pressure were collected annually during a 5-year period from 4360 Japanese workers with ages ranging from 19 to 55 years. Estimates of 24-h sodium and potassium excretion were based on Tanaka’s formula. Overall, a single standard deviation increase in the estimated sodium excretion (36.5 mmol/day) was associated with a 1.3 mmHg higher systolic blood pressure and a 0.8 mmHg higher diastolic blood pressure (P < 0.001). A single standard deviation increase in estimated potassium excretion (8.9 mmol/day) was associated with a 1.1 mmHg lower systolic blood pressure and a 0.7 mmHg lower diastolic blood pressure (P < 0.001). As a combined measure of the excretion of both electrolytes, the estimated 24-h sodium-to-potassium ratio was positively associated with both blood pressures (P < 0.001). Associations of blood pressure with sodium and the sodium-to-potassium ratio increased with age and were stronger in men compared to women. Associations with potassium and the sodium-to-potassium ratio were stronger in individuals who were overweight. The findings provide evidence for an association between blood pressure and the estimated 24-h sodium and potassium excretion from repeated single-spot urine samples. As convenient measures of dietary intake for each electrolyte, repeated spot urine samples may be useful for assessing hypertension risk, especially in men, older individuals, and overweight individuals.

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Does social interaction influence the effect of cognitive intervention program? A randomized controlled trial using Go game

Iizuka A., Suzuki H., Ogawa S., Kobayashi-Cuya K., Kobayashi M., Inagaki H., Sugiyama M., Awata S., Takebayashi T., Fujiwara Y.

International Journal of Geriatric Psychiatry （International Journal of Geriatric Psychiatry） 34 （ 2 ） 324 - 332 2019年02月

ISSN 08856230

© 2018 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd. Objectives: The purpose of this study is to clarify the influence of social interaction on the effect of a cognitive intervention program using Go. Methods: A single-blind, randomized controlled trial using a classical board game “Go” was conducted. A total of 72 community-dwelling older adults, without previous experience playing Go, were randomly assigned to three groups: (1) a face-to-face group (FG) in which members attended 12 Go group lessons held once a week; (2) a non-face-to-face group (NFG) in which members individually underwent the same Go lessons as the FG using a tablet computer; or (3) a health education control group (CG). The main outcome variable, working memory, was assessed before and after the interventions using the Visual Memory Span Test (VMST) and the Visual Memory Span Backward (VMSB) task. Go performance and additional cognitive domains were also examined. Results: Analysis of covariance revealed that VMST scores significantly improved after the intervention in both the FG and NFG (both P <.05). Compared with the CG, the effect size of the FG (Cohen's d = 0.89) was greater than that of the NFG (Cohen's d = 0.67). Although VMSB scores significantly improved after the intervention in the FG (P <.05), no significant changes were observed in other groups. Conclusions: This study showed that Go game could improve visual working memory regardless of social interaction. Furthermore, findings suggested that playing board games face-to-face with others is more effective for cognitive function than playing alone.

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Biological monitoring of o-toluidine in urine pretreated by an enzymatic deconjugation method

Eitaki Y., Nakano M., Kawai T., Omae K., Takebayashi T.

Journal of Occupational Health （Journal of Occupational Health） 2019年

ISSN 13419145

© 2019 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health Objectives: To establish an enzymatic deconjugation method to separately quantify urinary o-toluidine (OT), its six metabolites, another six chemicals present in an OT-processing plant, and one metabolite of p-toluidine, and to propose optimal urinary biological monitoring items of OT exposure. Methods: Thirty-six urine samples of an OT-processing plant's workers were obtained and pretreated by an enzymatic deconjugation method employing β-glucuronidase/arylsulfatase for 3 hours at 37°C and measured by liquid chromatograph-mass spectrometry (LC-MS). An alkaline hydrolytic pretreatment and 1-chlorobutane extraction procedure was also examined as a widely used urinary OT measurement method. Results: The 14 chemicals were separated by LC-MS condition set by us and 13 chemicals other than 2-chloroaniline showed satisfiable linearity and limits of determination. Standard substances of six OT metabolites decomposed after the alkaline heating. In the 36 urine samples, OT, N-(4-hydroxy-2-methylphenyl) acetamide (NHM), and 4-amino-m-cresol (ACR) accounted for approx. 90% of the total OT and OT metabolites, but inter-individual variation of the three substance excretion seemed to be wide. Time course of urinary excretion revealed that concentration of the three substances was higher 24 hours after the work shift's end rather than just after the work shift. Conclusions: OT and its six metabolites can each be determined with LC-MS. The alkaline method is not so optimal for exact biological monitoring. Rather, the sum of urinary OT, NHM, and ACR measured by the enzymatic method is a better index, and "end of the workweek" is a good urine-sampling time for the biological monitoring of OT exposure.

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Clinical differences between elderly-onset ulcerative colitis and non-elderly-onset ulcerative colitis: A nationwide survey data in Japan

Komoto S., Higashiyama M., Watanabe C., Suzuki Y., Watanabe M., Hibi T., Takebayashi T., Asakura K., Nishiwaki Y., Miura S., Hokari R.

Journal of Gastroenterology and Hepatology (Australia) （Journal of Gastroenterology and Hepatology (Australia)） 33 （ 11 ） 1839 - 1843 2018年11月

ISSN 08159319

© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd Background and Aim: Studies on the characteristics of elderly-onset ulcerative colitis (EOUC) and non-elderly-onset ulcerative colitis (NEOUC) have reported conflicting findings. The aim of this study was to compare disease characteristics of EOUC and NEOUC by analyzing the database of the Japanese nationwide inflammatory bowel disease (IBD) registry. Methods: We analyzed the age of disease onset, sex, disease severity, and disease extent in patients with ulcerative colitis that were newly diagnosed and registered within 1 year between 2004 and 2009 (n = 28 179). We also analyzed the medical treatment, rate of IBD-related surgery, and postoperative complications. We compared them between younger than 65 years old (NEOUC group) and 65 years old or older (EOUC group) patients. Results: A total of 25 401 (90.1%) and 2778 (9.9%) patients were included in the NEOUC and EOUC groups, respectively. In the EOUC group, disease activity was significantly higher, and extent of pathological changes in the colon more extended significantly. Laboratory findings showed that inflammatory markers were elevated significantly in the EOUC group. The proportion of those with IBD-related hospitalization was significantly higher in the EOUC group (54.2% vs 35.7%, P < 0.001). The proportion of patients who were treated with corticosteroids was significantly higher in the EOUC group (36.7% vs 30.8%, P < 0.001). Significantly more number of patients underwent IBD-related surgery in the EOUC group (0.68% vs 0.27%, P < 0.001). Conclusion: Elderly patients show higher disease activity, with a higher proportion requiring IBD-related hospitalization and IBD-related surgery, according to the nationwide registry in Japan.

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Hand dexterity, not handgrip strength, is associated with executive function in Japanese community-dwelling older adults: a cross-sectional study

武林亨

BMC GERIATRICS 18 2018年08月

研究論文（学術雑誌）, ISSN 1471-2318

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An epidemic of bladder cancer: ten cases of bladder cancer in male Japanese workers exposed to ortho-toluidine

武林亨

JOURNAL OF OCCUPATIONAL HEALTH 60 （ 4 ） 307 - 311 2018年07月

研究論文（学術雑誌）, ISSN 1341-9145

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Falls and Physical Inactivity in Patients with Gastrointestinal Cancer and Hand-Foot Syndrome

Komatsu H., Yagasaki K., Hamamoto Y., Takebayashi T.

Asia-Pacific Journal of Oncology Nursing （Asia-Pacific Journal of Oncology Nursing） 5 （ 3 ） 307 - 313 2018年07月

ISSN 23475625

© 2018 Medknow. All rights reserved. Objective: This study aims to ascertain the incidence and association of falls and physical inactivity in patients with gastrointestinal cancer and hand-foot syndrome (HFS) after receiving chemotherapy or targeted therapy. Methods: The present cross-sectional study was conducted on 50 outpatients with HFS of Grade 1 or above, according to the National Cancer Institute Common Terminology Criteria for Adverse Events, following the receipt of chemotherapy or targeted therapy for gastrointestinal cancer in Japan between November 2016 and February 2017. For measurement, Dermatology Life Quality Index (DLQI) and the International Physical Activity Questionnaire were used. Data were analyzed by logistic regression analysis. Results: Of the participants, 18% experienced falls and 60% reported physical inactivity. Multivariate logistic regression revealed that the DLQI treatment domain score was the only factor associated with falls (odds ratio [OR] =8.01, 95% confidence interval [CI] =1.27-50.63, P = 0.027). Physical inactivity was associated with DLQI symptom and feeling domain scores (OR = 5.54, 95% CI = 1.26-24.33, P = 0.023) and the with-oxaliplatin or paclitaxel regimen (OR = 3.71, 95% CI = 1.06-13.03, P = 0.041). Conclusions: The results of the present study suggest patients should be informed that HFS is a risk factor for physical inactivity and falls.

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Pilot Randomized Controlled Trial of the GO Game Intervention on Cognitive Function

武林亨

AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS 33 （ 3 ） 192 - 198 2018年05月

研究論文（学術雑誌）, ISSN 1533-3175

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Association Between Knee Pain, Impaired Function, and Development of Depressive Symptoms

武林亨

JOURNAL OF THE AMERICAN GERIATRICS SOCIETY 66 （ 3 ） 570 - 576 2018年03月

研究論文（学術雑誌）, ISSN 0002-8614

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Community-wide physical activity intervention based on the Japanese physical activity guidelines for adults: A non-randomized controlled trial

武林亨

PREVENTIVE MEDICINE 107 61 - 68 2018年02月

研究論文（学術雑誌）, ISSN 0091-7435

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Gender-specific association of early age-related macular degeneration with systemic and genetic factors in a Japanese population

武林亨

SCIENTIFIC REPORTS 8 61 - 68 2018年01月

研究論文（学術雑誌）, ISSN 2045-2322

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Reliability of plasma polar metabolite concentrations in a large-scale cohort study using capillary electrophoresis-mass spectrometry

武林亨

PLOS ONE 13 （ 1 ） 61 - 68 2018年01月

研究論文（学術雑誌）, ISSN 1932-6203

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Carotid Plaque Score and Risk of Cardiovascular Mortality in the Oldest Old: Results from the TOOTH Study

武林亨

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS 25 （ 1 ） 55 - 64 2018年

研究論文（学術雑誌）, ISSN 1340-3478

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Observational Evidence of the Association Between Handgrip Strength, Hand Dexterity, and Cognitive Performance in Community-Dwelling Older Adults: A Systematic Review

武林亨

JOURNAL OF EPIDEMIOLOGY 28 （ 9 ） 373 - 381 2018年

研究論文（学術雑誌）, ISSN 0917-5040

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Association of high individual-level of social capital with increased physical activity among community-dwelling elderly men and women: A cross-sectional study

Saito Y., Oguma Y., Tajima T., Kato R., Kibayashi Y., Miyachi M., Takebayashi T.

Japanese Journal of Physical Fitness and Sports Medicine （Japanese Journal of Physical Fitness and Sports Medicine） 67 （ 2 ） 177 - 185 2018年

ISSN 0039906X

We aimed to evaluate the associations of individual-level social capital (SC) and physical activity (PA) among Japanese elderly men and women. Individuals aged 65 or above were selected via population-based random sampling of 3000 adults, aged 20 years or above and living in Fujisawa city, who were asked to complete self-administered questionnaires. The sample consisted of 260 men [median (25-75% tile) age 73 (68-78) yrs] and 274 women [73 (68-78) yrs]. The daily duration of PA, SC [e.g., norms of reciprocity (mutual support in the community), social networks (relationship with community people, exchange with other generations), social participation (participation in community organization activities)], socio-economic status [educational attainment, work with income, perceived household economic status], and demographic characteristics [sex, age, living arrangements, BMI, physical limitations] were assessed. Multivariate logistic regression analyses were used to calculate odds ratios (OR) for associations of SC with PA, stratified by sex. High level of mutual support in the community, relationship with community people, and exchange with other generations were associated with longer PA time in men after adjusting for potential confounders in the final model (OR = 2.40 (95% CI: 1.24-4.67), 5.28 (1.42-19.66), and 4.24 (1.15-15.67), respectively). In women, relationship with community people and participation in community organization activities were associated with longer PA time (3.10 (1.32-7.26) and 2.50 (1.27-4.91), respectively). The association of individual-level SC and PA differed between men and women. Future studies can investigate whether similar results can be obtained in other areas or attempt to conduct a large-scale survey.

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Needs survey on the priority given to periodical medical examination items among occupational physicians in Japan

Ito N., Nagata T., Tatemichi M., Takebayashi T., Mori K.

Journal of Occupational Health （Journal of Occupational Health） 60 （ 6 ） 502 - 514 2018年

ISSN 13419145

© Article author(s). Objectives: To clarify the priority given to periodical medical examination items among occupational physicians in Japan. Methods: Sixty-two occupational physicians who participated in this study selected statutory and non-statutory items within two types of budget plans: one lower (8,500 yen) than the total fee of statutory medical examinations (9,250 and 11,290 yen), and the other higher (12,000 yen) than the total fee. Medical fee points were used to set the cost of each medical examination item. A three round Delphi method was used from May to July 2016 to clarify the consensus opinion of occupational physicians. Results: The statutory items (selection rate: between 66 and 100%), except for waist circumference (15%) and sputum examination (0%), and serum creatinine (58%, non-statutory item ) were included in the smaller budget plan (8,500 yen) . In the larger budget plan (12,000 yen), the statutory items (selection rate: between 92 and 100%), except for waist circumference (39%) and sputum examination (0%), and some non-statutory items, namely serum creatinine (95%), leukocytes (92%), uric acid (89%), and fecal occult blood reaction (81%), had a selection rate over 80%. In addition, statutory items with higher accuracy were preferred, which included the following: air conduction pure-tone audiometry (92%), imaging diagnosis of thoracic X-ray examinations by a specialist (97%), glycated hemoglobin levels (98%), and electrocardiogram assessment by a specialist (100%). Conclusion: The statutory items, except for waist circumference and sputum examination, and some of the non-statutory items (e.g., serum creatinine ) were given higher priority among occupational physicians in Japan.

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Relationship Between Depressive Symptoms and Activity of Daily Living Dependence in Older Japanese: The Kurabuchi Study

武林亨

JOURNAL OF THE AMERICAN GERIATRICS SOCIETY 65 （ 12 ） 2639 - 2645 2017年12月

研究論文（学術雑誌）, ISSN 0002-8614

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Effects of a school-based stroke education program on stroke-related knowledge and behaviour modification-school class based intervention study for elementary school students and parental guardians in a Japanese rural area

武林亨

BMJ OPEN 7 （ 12 ） 61 - 68 2017年12月

研究論文（学術雑誌）, ISSN 2044-6055

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Comparison of the efficacy of three topical antiseptic solutions for the prevention of catheter colonization: a multicenter randomized controlled study

武林亨

CRITICAL CARE 21 55 - 64 2017年12月

研究論文（学術雑誌）, ISSN 1466-609X

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The association of kyphosis assessed in supine and standing positions with future activities of daily living dependence: the Kurabuchi Study

武林亨

ARCHIVES OF OSTEOPOROSIS 12 （ 1 ） 2639 - 2645 2017年11月

研究論文（学術雑誌）, ISSN 1862-3522

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Influence of sulfur dioxide on the respiratory system of Miyakejima adult residents 6 years after returning to the island

武林亨

JOURNAL OF OCCUPATIONAL HEALTH 59 （ 4 ） 313 - 326 2017年07月

研究論文（学術雑誌）, ISSN 1341-9145

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Occupational exposure limits for ethylene glycol monobutyl ether, isoprene, isopropyl acetate and propyleneimine, and classifications on carcinogenicity, occupational sensitizer and reproductive toxicant

武林亨

JOURNAL OF OCCUPATIONAL HEALTH 59 （ 4 ） 364 - 366 2017年07月

研究論文（学術雑誌）, ISSN 1341-9145

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Optimal plateau pressure for patients with acute respiratory distress syndrome: a protocol for a systematic review and meta-analysis with meta-regression

武林亨

BMJ OPEN 7 （ 5 ） 313 - 326 2017年05月

研究論文（学術雑誌）, ISSN 2044-6055

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Association Between Estimated 24-hour Urinary Sodium and Potassium Excretion and Blood Pressure in a Japanese Cohort: a Repeated Measure Analysis

武林亨

CIRCULATION 135 187 - 193 2017年03月

研究論文（学術雑誌）, ISSN 0009-7322

Changes of median nerve conduction velocity in rayon manufacturing workers: A 6-year cohort study

武林亨

JOURNAL OF OCCUPATIONAL HEALTH 59 （ 2 ） 187 - 193 2017年03月

研究論文（学術雑誌）, ISSN 1341-9145

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Changes of median nerve conduction velocity in rayon manufacturing workers: A 6-year cohort study

武林亨

JOURNAL OF OCCUPATIONAL HEALTH 59 （ 2 ） 187 - 193 2017年03月

研究論文（学術雑誌）, ISSN 1341-9145

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Identification of adverse events that have a negative impact on quality of life in a clinical trial comparing docetaxel versus S-1 with cisplatin in lung cancer

武林亨

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 21 （ 5 ） 836 - 842 2016年10月

研究論文（学術雑誌）, ISSN 1341-9625

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Metabolic Profiling of Total Physical Activity and Sedentary Behavior in Community-Dwelling Men

武林亨

PLOS ONE 11 （ 10 ） 385 - 387 2016年10月

研究論文（学術雑誌）, ISSN 1932-6203

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Relationships of Community and Individual Level Social Capital with Activities of Daily Living and Death by Gender

武林亨

INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 13 （ 9 ） 836 - 842 2016年09月

研究論文（学術雑誌）, ISSN 1660-4601

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Profiling of plasma metabolites in postmenopausal women with metabolic syndrome

武林亨

MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY 23 （ 7 ） 749 - 758 2016年07月

研究論文（学術雑誌）, ISSN 1072-3714

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Occupational Exposure Limits of lead, dimethylamine, n-butyl-2,3-epoxypropyl ether, and 2-ethyl-1-hexanol and carcinogenicity and occupational sensitizer classification

武林亨

JOURNAL OF OCCUPATIONAL HEALTH 58 （ 4 ） 385 - 387 2016年07月

研究論文（学術雑誌）, ISSN 1341-9145

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Cross-sectional association between exposure to particulate matter and inflammatory markers in the Japanese general population: NIPPON DATA2010

武林亨

ENVIRONMENTAL POLLUTION 213 460 - 467 2016年06月

研究論文（学術雑誌）, ISSN 0269-7491

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A self-directed home yoga programme for women with breast cancer during chemotherapy: A feasibility study

武林亨

INTERNATIONAL JOURNAL OF NURSING PRACTICE 22 （ 3 ） 258 - 266 2016年06月

研究論文（学術雑誌）, ISSN 1322-7114

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Carotid atherosclerosis, cytomegalovirus infection, and cognitive decline in the very old: a community-based prospective cohort study

武林亨

AGE 38 （ 2 ） S265 - S265 2016年04月

研究論文（学術雑誌）, ISSN 0161-9152

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Association of baseline plasma des-acyl ghrelin level with the response to rikkunshito in patients with functional dyspepsia

武林亨

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 31 （ 2 ） 334 - 341 2016年02月

研究論文（学術雑誌）, ISSN 0815-9319

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Effects of processing and storage conditions on charged metabolomic profiles in blood

Hirayama Akiyoshi, Sugimoto Masahiro, Suzuki Asako, Hatakeyama Yoko, Enomoto Ayame, Harada Sei, Soga Tomoyoshi, Tomita Masaru, Takebayashi Toru

Electrophoresis 36 （ 18 ） 2148 - 2155 2015年09月

研究論文（学術雑誌）, 共著, ISSN 0173-0835

The development of high-throughput metabolite measurement technologies has enabled the use of metabolomics for epidemiologic studies by profiling metabolite concentrations in large cohorts of human blood samples. Standard protocols are necessary to obtain unbiased profiles through multiple runs over long periods of time and to allow reliable statistical analyses. This study assessed the effects of sampling procedures and storage conditions on the stability of metabolomic profiles in plasma and serum. Charged metabolomic profiles were determined by capillary electrophoresis-mass spectrometry (CE-MS) and compared by multivariate analyses. The effects of pre-analytical procedures, including times for clotting and incubation of serum and plasma, respectively; incubation temperatures; and number of freeze-thaw cycles, were assessed. Overall, inter-individual differences in profiles were larger than intra-individual differences, and profiles in plasma showed better stability than those in serum. These quantified datasets of metabolites, along with their stability and variation, may help in interpreting data from long-term cohort studies.

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The effects of community-wide dissemination of information on perceptions of palliative care, knowledge about opioids, and sense of security among cancer patients, their families, and the general public

Akiyama Miki, Hirai Kei, Takebayashi Toru, Morita Tatsuya, Miyashita Mitsunori, Takeuchi Ayano, Yamagishi Akemi, Kinoshita Hiroya, Shirahige Yutaka, Eguchi Kenji

Supportive Care in Cancer 2015年06月

研究論文（学術雑誌）, 共著, ISSN 0941-4355

Purpose: Prejudices against palliative care are a potential barrier to quality end-of-life care. There have been few large-scale community-wide interventions to distribute appropriate information about palliative care, and no studies have investigated their impact on cancer patients, their families, and the general public. Thus, we conducted a 3-year community intervention and evaluated the effects of distributing such information at the community level, and explored associations among levels of exposure, perceptions, knowledge, and the sense of security achieved. Methods: Over a period of 3 years, we provided flyers, booklets, posters, and public lectures about palliative care in four regions of Japan, and carried out pre- and post-intervention surveys with repeated cross-sectional samplings of cancer patients (pre 859, post 857), bereaved family members (1110, 1137), and the general public (3984, 1435). The levels of exposure to the provided information were measured by a multiple-choice questionnaire after intervention. Multiple logistic regression analyses were used to estimate multivariable-adjusted odds ratios (ORs) for perceptions of palliative care, knowledge about opioids, and sense of security among the exposure groups. Results: Overall perceptions of palliative care, opioids, and receiving care at home improved significantly among the general public and families, but not among the patients at the community level. However, multiple regression revealed that patients of extensive exposure category had significantly more positive perceptions of palliative care to those of non-exposure category (p = 0.02). The sense of security regarding cancer care of all patients, family members, and the general public improved. Among others, the respondents who reported extensive exposure in the general public and family members scored significantly higher sense of security. Conclusion: Our findings indicate that providing palliative care information via small media and lectures in the community is effective in improving perceptions of palliative care and knowledge about opioids among the community dwellers, especially for caregivers of the patients. The acquisition of adequate knowledge about palliative care from various information sources may improve people’s sense of security regarding cancer.

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Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age

Arai Yasumichi, Martin-Ruiz Carmen M., Takayama Michiyo, Abe Yukiko, Takebayashi Toru, Koyasu Shigeo, Suematsu Makoto, Hirose Nobuyoshi, von Zglinicki Thomas

EBioMedicine 2015年06月

研究論文（学術雑誌）, 共著

To determine the most important drivers of successful ageing at extreme old age, we combined community-based prospective cohorts: Tokyo Oldest Old Survey on Total Health (TOOTH), Tokyo Centenarians Study (TCS) and Japanese Semi-Supercentenarians Study (JSS) comprising 1554 individuals including 684 centenarians and (semi-)supercentenarians, 167 pairs of centenarian offspring and spouses, and 536 community-living very old (85 to 99years). We combined z scores from multiple biomarkers to describe haematopoiesis, inflammation, lipid and glucose metabolism, liver function, renal function, and cellular senescence domains. In Cox proportional hazard models, inflammation predicted all-cause mortality with hazard ratios (95% CI) 1.89 (1.21 to 2.95) and 1.36 (1.05 to 1.78) in the very old and (semi-)supercentenarians, respectively. In linear forward stepwise models, inflammation predicted capability (10.8% variance explained) and cognition (8.6% variance explained) in (semi-)supercentenarians better than chronologic age or gender. The inflammation score was also lower in centenarian offspring compared to age-matched controls with δ (95% CI)=-0.795 (-1.436 to -0.154). Centenarians and their offspring were able to maintain long telomeres, but telomere length was not a predictor of successful ageing in centenarians and semi-supercentenarians. We conclude that inflammation is an important malleable driver of ageing up to extreme old age in humans.

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Relationship of type of work with health-related quality of life

Kawabe Yuri, Nakamura Yasuyuki, Kikuchi Sayuri, Suzukamo Yoshimi, Murakami Yoshitaka, Tanaka Taichiro, Takebayashi Toru, Okayama Akira, Miura Katsuyuki, Okamura Tomonori, Fukuhara Shunichi, Ueshima Hirotsugu

Quality of Life Research 2015年06月

研究論文（学術雑誌）, 共著, ISSN 0962-9343

Purpose: To examine the relation of work type with health-related quality of life (HRQoL) in healthy workers. Methods: We cross-sectionally examined 4427 (3605 men and 822 women) healthy workers in Japan, aged 19–69 years. We assessed HRQoL based on scores for five scales of the SF-36. Multiple regression was applied to examine the relation of work type (nighttime, shift, day to night, and daytime) with the five HRQoL norm-based scores, lower scores of which indicate poorer health status, adjusted for confounding factors, including sleeping duration. Results: Shiftwork was inversely related to role physical [regression estimate (β) = −2.12, 95 % confidence intervals (CI) −2.94, −1.30, P < 0.001], general health (β = −1.37, 95 % CI −2.01, −0.72, P < 0.001), role emotional (β = −1.24, 95% CI −1.98, −0.50, P < 0.001), and mental health (β = −1.31, 95% CI −2.01, −0.63, P < 0.001) independent of confounding factors, but not to vitality. Day-to-nighttime work was inversely related to all the five HRQoL subscales (Ps 0.012 to <0.001). Conclusion: Shiftwork was significantly inversely related to four out of the five HRQoL, except for vitality, and day-to-nighttime work was significantly inversely related to all five HRQoL, independent of demographic and lifestyle factors.

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Physical Activity, Fitness And Cognitive Function Among Community-dwelling Elderly - baseline Data Of Fujisawa Plusten Project.

武林亨

MEDICINE AND SCIENCE IN SPORTS AND EXERCISE 47 （ 5 ） 216 - 216 2015年05月

研究論文（学術雑誌）, ISSN 0195-9131

Denture wearing during sleep doubles the risk of pneumonia in the very elderly

Iinuma T., Arai Y., Abe Y., Takayama M., Fukumoto M., Fukui Y., Iwase T., Takebayashi T., Hirose N., Gionhaku N., Komiyama K.

Journal of Dental Research 94 28S - 36S 2015年03月

研究論文（学術雑誌）, 共著, ISSN 0022-0345

Poor oral health and hygiene are increasingly recognized as major risk factors for pneumonia among the elderly. To identify modifiable oral health-related risk factors, we prospectively investigated associations between a constellation of oral health behaviors and incident pneumonia in the community-living very elderly (i.e., 85 years of age or older). At baseline, 524 randomly selected seniors (228 men and 296 women; mean age, 87.8 years) were examined for oral health status and oral hygiene behaviors as well as medical assessment, including blood chemistry analysis, and followed up annually until first hospitalization for or death from pneumonia. During a 3-year follow-up period, 48 events associated with pneumonia (20 deaths and 28 acute hospitalizations) were identified. Among 453 denture wearers, 186 (40.8%) who wore their dentures during sleep were at higher risk for pneumonia than those who removed their dentures at night (log rank P = 0.021). In a multivariate Cox model, both perceived swallowing difficulties and overnight denture wearing were independently associated with an approximately 2.3-fold higher risk of the incidence of pneumonia (for perceived swallowing difficulties, hazard ratio [HR], 2.31; and 95% confidence interval [CI], 1.11-4.82; and for denture wearing during sleep, HR, 2.38; and 95% CI, 1.25-4.56), which was comparable with the HR attributable to cognitive impairment (HR, 2.15; 95% CI, 1.06-4.34), history of stroke (HR, 2.46; 95% CI, 1.13-5.35), and respiratory disease (HR, 2.25; 95% CI, 1.20-4.23). In addition, those who wore dentures during sleep were more likely to have tongue and denture plaque, gum inflammation, positive culture for Candida albicans, and higher levels of circulating interleukin-6 as compared with their counterparts. This study provided empirical evidence that denture wearing during sleep is associated not only with oral inflammatory and microbial burden but also with incident pneumonia, suggesting potential implications of oral hygiene programs for pneumonia prevention in the community.

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Place of death and the differences in patient quality of death and dying and caregiver burden

Kinoshita Hiroya, Maeda Isseki, Morita Tatsuya, Miyashita Mitsunori, Yamagishi Akemi, Shirahige Yutaka, Takebayashi Toru, Yamaguchi Takuhiro, Igarashi Ayumi, Eguchi Kenji

Journal of Clinical Oncology 33 （ 4 ） 357 - 363 2015年02月

研究論文（学術雑誌）, 共著, ISSN 0732-183X

Purpose To explore the associations between place of death and quality of death and dying and caregiver burden in terminally ill patients with cancer and their families. Methods Two bereavement surveys were conducted in October 2008 and October 2011. A total of 2,247 family caregivers of patients with cancer who were deceased responded to the mail surveys (response rate, 67%). Family members reported patient quality of death and dying and caregiver burden by using the Good Death Inventory and Caregiving Consequences Inventory. Results Patient quality of death and dying was significantly higher at home relative to other places of dying after adjustment for patient and/or family characteristics (adjusted means): 5.0 (95% CI, 4.9 to 5.2) for home, 4.6 (95% CI, 4.5 to 4.7) for palliative care units, and 4.3 (95% CI, 4.2 to 4.4) for hospitals. For all combinations, pairwise P < .001; the size of the difference between home and hospital was moderate (Hedges' g, 0.45). Home was superior to palliative care units or hospitals with respect to " dying in a favorite place," " good relationships with medical staff," " good relationships with family, " and " maintaining hope and pleasure " ( P < .001 for all combinations of home v palliative care units and home v hospitals). Home death was significantly associated with a lower overall (P = .03) and financial caregiver burden ( P = .004) relative to hospital death. Conclusion Dying at home may contribute to achieving good death in terminally ill patients with cancer without causing remarkably increased caregiver burden. Place of death should be regarded as an essential goal in end-of-life care.

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Cost-effectiveness of adding rituximab to splenectomy and romiplostim for treating steroid-resistant idiopathic thrombocytopenic purpura in adults

Kikuchi, Kayoko, Miyakawa, Yoshitaka, Ikeda, Shunya, Sato, Yuji, Takebayashi, Toru

BMC Health Services Research 15 （ 1 ） 2015年01月

研究論文（学術雑誌）, ISSN 1472-6963

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Grading criteria for disease severity by pemphigus disease area index

Shimizu Tomoko, Takebayashi Toru, Sato Yuji, Niizeki Hironori, Aoyama Yumi, Kitajima Yasuo, Iwatsuki Keiji, Hashimoto Takashi, Yamagami Jun, Werth Victoria P., Amagai Masayuki, Tanikawa Akiko

Journal of Dermatology 41 （ 11 ） 969 - 973 2014年11月

研究論文（学術雑誌）, 共著, ISSN 0385-2407

Pemphigus is a group of autoimmune blistering diseases that affect the skin and mucous membranes. A reliable and accurate disease severity tool to assess pemphigus severity is crucial for managing pemphigus and for clinical trials. The purpose of this study was to compare the pemphigus disease area index activity score (PDAI), the Japanese pemphigus disease severity score (JPDSS) and the physician's subjective impression, and also to find appropriate severity grading cut-offs for the PDAI. We also evaluated the correlation between PDAI activity score and the JPDSS. Thirty-seven pemphigus patients and 110 assessments were analyzed in this study. The optimal points of pemphigus disease severity score in PDAI were: mild (0-8), moderate (9-24) and severe (≥25). In mild or moderate cases, the JPDSS was well correlated with the PDAI, but in severe cases the JPDSS reached a plateau at a PDAI score of approximately 30. The PDAI evaluates disease severity more accurately than the JPDSS, particularly in severe cases. The PDAI is not only a useful tool to measure the extent of cutaneous lesions, but also an excellent scoring system for evaluating pemphigus disease severity.

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Circulating AIM as an indicator of liver damage and hepatocellular carcinoma in humans

Yamazaki Tomoko, Mori Mayumi, Arai Satoko, Tateishi Ryosuke, Abe Masanori, Ban Mihoko, Nishijima Akemi, Maeda Maki, Asano Takeharu, Kai Toshihiro, Izumino Kiyohiro, Takahashi Jun, Aoyama Kayo, Harada Sei, Takebayashi Toru, Gunji Toshiaki, Ohnishi Shin, Seto Shinji, Yoshida Yukio, Hiasa Yoichi, Koike Kazuhiko, Yamamura Ken Ichi, Inoue Ken Ichiro, Miyazaki Toru

PLoS ONE 9 （ 10 ） 2014年10月

研究論文（学術雑誌）, 共著

Background: Hepatocellular carcinoma (HCC), the fifth most common cancer type and the third highest cause of cancer death worldwide, develops in different types of liver injuries, and is mostly associated with cirrhosis. However, non-alcoholic fatty liver disease often causes HCC with less fibrosis, and the number of patients with this disease is rapidly increasing. The high mortality rate and the pathological complexity of liver diseases and HCC require blood biomarkers that accurately reflect the state of liver damage and presence of HCC. Methods and Findings: Here we demonstrate that a circulating protein, apoptosis inhibitor of macrophage (AIM) may meet this requirement. A large-scale analysis of healthy individuals across a wide age range revealed a mean blood AIM of 4.99±1.8 μg/ml in men and 6.06±2.1 μg/ml in women. AIM levels were significantly augmented in the younger generation (20s-40s), particularly in women. Interestingly, AIM levels were markedly higher in patients with advanced liver damage, regardless of disease type, and correlated significantly with multiple parameters representing liver function. In mice, AIM levels increased in response to carbon tetrachloride, confirming that the high AIM observed in humans is the result of liver damage. In addition, carbon tetrachloride caused comparable states of liver damage in AIM-deficient and wild-type mice, indicating no influence of AIM levels on liver injury progression. Intriguingly, certain combinations of AIM indexes normalized to liver marker score significantly distinguished HCC patients from non-HCC patients and thus could be applicable for HCC diagnosis. Conclusion: AIM potently reveals both liver damage and HCC. Thus, our results may provide the basis for novel diagnostic strategies for this widespread and fatal disease.

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Obesity was associated with a decreased postoperative recurrence of rectal cancer in a Japanese population

Seishima Ryo, Okabayashi Koji, Hasegawa Hirotoshi, Sugiyama Daisuke, Ishii Yoshiyuki, Tsuruta Masashi, Takebayashi Toru, Kitagawa Yuko

Surgery Today 2014年05月

研究論文（学術雑誌）, 共著, ISSN 0941-1291

Purpose Obesity contributes to the technical difficulty of rectal surgery and is considered to be a risk factor for postoperative complications. The impact of obesity on the long-term outcomes of rectal cancer surgery remains unclear. Methods A total of 263 consecutive rectal cancer patients who underwent surgery were categorized into two groups according to the body mass index (BMI) based on the Asian BMI classification: non-obese (BMI <25 kg/m²) and obese (BMI ≥25 kg/m²). The postoperative survival and recurrence rates and oncological surgical quality indicators were compared between groups using the univariate and multivariate analyses. The differences in recurrence patterns were assessed by a competing risk regression analysis. Results 64 (24 %) patients were included in the obese group. The number of retrieved lymph nodes was significantly greater in the non-obese group than in the obese group (22.4 vs. 16.0, P < 0.01). The 5-year disease-free survival (DFS) rates were 86.5 and 68.8 % in the obese and non-obese groups, respectively (P = 0.01). The multivariate analysis demonstrated that obesity significantly decreased the postoperative recurrence rate (P = 0.04). Moreover, the BMI was significantly associated with distant metastasis (P = 0.04). Conclusions Obese rectal cancer patients have high DFS rates and a decreased incidence of distant metastases compared to non-obese patients. The BMI may be a key factor for predicting the postoperative prognosis and determination of an appropriate strategy for the treatment of rectal cancer patients. © 2014 Springer Japan.

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Efficacy and Safety of Rikkunshito, a Japanese Herbal Medicine, on the Treatment of Functional Dyspepsia: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study

武林亨

GASTROENTEROLOGY 146 （ 5 ） S265 - S265 2014年05月

研究論文（学術雑誌）, ISSN 0016-5085

Steeper increases in body mass index during childhood correlate with blood pressure elevation in adolescence

Kuwahara Erika, Asakura Keiko, Nishiwaki Yuji, Komatsu Hirokazu, Nakazawa Akemi, Ushiku Hideo, Maejima Fumio, Nishigaki Yoshio, Hasegawa Tomonobu, Okamura Tomonori, Takebayashi Toru

Hypertension Research 37 （ 2 ） 179 - 184 2014年02月

研究論文（学術雑誌）, 共著, ISSN 0916-9636

The aim of this study was to clarify the relationship between long-term changes in body mass index (BMI) during childhood and adolescent blood-pressure levels in a general Japanese population. We used health report data from 900 Japanese children between 1983 and 2007. After adjusting for baseline BMI and other confounding factors multivariate linear regression analyses were performed to examine the relationship between changes in BMI (ΔBMI) over a 6-year period (6-12 years) and blood pressure once children reached ages 14 or 15. Sub-group analyses were also performed to ascertain the relationship between ΔBMI and blood pressure at 9th grade for children who had been in the bottom BMI tertile at 1st grade. Endpoint blood-pressure levels in boys (systolic and diastolic) and girls (systolic) from the group whose BMIs increased the most were significantly higher than those from the group whose BMIs increased the least (P<0.05, analysis of variance). After adjustment for baseline BMI and school-entrance year, the former group showed higher blood pressure at the endpoint than the latter (P<0.05, multiple regression analysis). Further adjustment for baseline blood pressure also showed similar results in a combined-sex analysis (n=592). Higher ΔBMI was associated with higher SBP 9 even in children whose BMI was in the lowest tertile at baseline after adjustment for sex and school-entrance year (P=0.02, multiple regression analysis). Steeper BMI increases during primary school lead to adolescent increases in blood pressure even if baseline BMI is low. Growth during childhood should be carefully managed. © 2014 The Japanese Society of Hypertension All rights reserved.

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Effect size and cost-effectiveness estimates of breast and cervical cancer screening reminders by population size through complete enumeration of Japanese local municipalities

Komoto Shigekazu, Nishiwaki Yuji, Okamura Tomonori, Tanaka Hideo, Takebayashi Toru

BMC Public Health 14 （ 1 ） 2014年01月

研究論文（学術雑誌）, 共著

Background: Client reminders are known to increase cancer screening attendance rates. However, there are significant costs associated with them, and their effect by population size is unknown. Methods. In 2007 and 2008, the Japanese Government surveyed breast and cervical cancer screening in every municipality in Japan. From the results, we selected all 1,464 municipalities that carried out both screening types. We examined whether changes in screening attendance rates between 2007 and 2008 were associated with client reminders, number of public health nurses per 100,000 population, financial strength index, and 2007 attendance rates for different population sizes. We then calculated cost-effectiveness estimates of client reminders by population size and screening type. Results: Client reminders were associated with increased attendance rates in populations <100,000. For populations of 50,000-100,000, there was a 2.76% increase in breast cancer screening (95% CI: 0.41, 5.11), and a 2.25% increase in cervical cancer screening (95% CI: 0.89, 3.61). The incremental cost per additional attendance was higher in populations <50,000 than in populations of 50,000-100,000 (breast, $100 versus $54; cervical, $149 versus $67 respectively). Conclusions: Client reminders for breast and cervical cancer screening increased attendance rates in smaller municipalities in Japan. © 2014 Komoto et al.; licensee BioMed Central Ltd.

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Relationship between shift work and clustering of the metabolic syndrome diagnostic components

Kawabe Yuri, Nakamura Yasuyuki, Kikuchi Sayuri, Murakami Yoshitaka, Tanaka Taichiro, Takebayashi Toru, Okayama Akira, Miura Katsuyuki, Okamura Tomonori, Ueshima Hirotsugu

Journal of Atherosclerosis and Thrombosis 21 （ 7 ） 703 - 711 2014年

研究論文（学術雑誌）, 共著, ISSN 1340-3478

Aim: To examine the relationship between the type of work and the number of metabolic syndrome diagnostic componentsS (MetS-DC), as well as the risk of MetS, with adjustment for lifestyle habits in Japanese workers. Methods: We examined the baseline data from 4,427 participants (81.4% male) aged 19 to 69 years old. The physical activity of each participant was classified according to the International Physical Activity Questionnaire (IPAQ). We defined the four MetS-DC in this study as follows: 1) high blood pressure (BP): systolic BP ≥ 130 mmHg, or diastolic BP ≥ 85 mmHg, or the use of antihypertensive drugs; 2) dyslipidemia: high-density lipoprotein-cholesterol concentration <40 mg/dl or triglyceride concentration ≥ 150 mg/dl, or on medication for dyslipidemia; 3) dysglycemia: fasting blood sugar level ≥ 110 mg/dl, or if less than eight hours after meals ≥ 140 mg/dl, or on medication for diabetes mellitus; 4) overweight: a body mass index ≥ 25 kg/m2. We defined MetS as overweight plus two or more of the MetS-DC. Results: There were 3,094 subjects in the daytime work group, 73 in the fixed nighttime work group, 1,017 in the shift work group and 243 in the day-to-night work group. The Poisson regression analysis revealed that fixed nighttime (regression coefficient [b] = -0.233, P=0.028) and shift work (b=0.098, P=0.034) independently contributed to the number of MetS-DC, compared to daytime work. The multivariate logistic analysis not including sleep hours in the model showed that shift work was positively related to MetS (odd ratio = 1.47, P<0.01). Conclusion: Shift work were significantly associated with the number of MetS-DC, and was related to risk of MetS compared to daytime work.

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Randomized clinical trial: rikkunshito in the treatment of functional dyspepsia—a multicenter, double-blind, randomized, placebo-controlled study

Suzuki H., Matsuzaki J., Fukushima Y., Suzaki F., Kasugai K., Nishizawa T., Naito Y., Hayakawa T., Kamiya T., Andoh T., Yoshida H., Tokura Y., Nagata H., Kobayakawa M., Mori M., Kato K., Hosoda H., Takebayashi T., Miura S., Uemura N., Joh T., Hibi T., Tack J., Kasugai Kunio, Nishizawa Toshihiro, Naito Yuji, Joh Takashi, Miura Soichiro, Uemura Naomi, Fukushima Yasushi, Suzaki Fumio, Hayakawa Toshihiko, Ando Takashi, Yoshida Hideo, Tokura Yoshifumi, Nagata Hiroshi, Kobayakawa Masao, Mori Mikiji, Kato Kimihiko, Tsuzuki Yoshikazu, Iwata Akihiro, Kobayashi Kunio, Imaeda Hiroyuki, Yamaguchi Yasuharu, Iwasaki Eisuke, Komatsu Hirokazu, Serizawa Hiroshi, Oyamada Yuichi, Yagou Yuzo, Yoshida Takeshi, Nishida Jiro, Yamamoto Sayuri, Tokita Kazuhiko

Neurogastroenterology and Motility 26 （ 7 ） 950 - 961 2014年

ISSN 1350-1925

Background: Rikkunshito, a standardized Japanese herbal medicine, is thought to accelerate gastric emptying and relieve dyspepsia, although no large-scale, randomized, placebo-controlled trials of rikkunshito have been conducted. This study aimed to determine the efficacy and safety of rikkunshito for treating functional dyspepsia (FD). Methods: FD patients received 2.5 g rikkunshito or placebo three times a day for 8 weeks in this multicenter, randomized, placebo-controlled, parallel-group trial. The primary end point was the proportion of responders at 8 weeks after starting test drug, determined by global patient assessment (GPA). The improvement in four major dyspepsia symptoms severity scale was also evaluated. In addition, plasma ghrelin levels were investigated before and after treatment. Key Results: Two hundred forty-seven patients were randomly assigned. In the eighth week, the rikkunshito group had more GPA responders (33.6%) than the placebo (23.8%), although this did not reach statistical significance (p = 0.09). Epigastric pain was significantly improved (p = 0.04) and postprandial fullness tended to improve (p = 0.06) in the rikkunshito group at week 8. Rikkunshito was relatively more effective among Helicobacter pylori-infected participants (rikkunshito: 40.0% vs placebo: 20.5%, p = 0.07), and seemed less effective among H. pylori-uninfected participants (rikkunshito: 29.3% vs placebo: 25.6%, p = 0.72). Among H. pylori-positive individuals, acyl ghrelin levels were improved just in rikkunshito group. There were no severe adverse events in both groups. Conclusions & Inferences: Administration of rikkunshito for 8 weeks reduced dyspepsia, particularly symptoms of epigastric pain and postprandial fullness. (UMIN Clinical Trials Registry, Number UMIN000003954). © 2014 John Wiley & Sons Ltd.

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Physical independence and mortality at the extreme limit of life span

Arai Yasumichi, Inagaki Hiroki, Takayama Michiyo, Abe Yukiko, Saito Yasuhiko, Takebayashi Toru, Gondo Yasuyuki, Hirose Nobuyoshi

Journals of Gerontology - Series A Biological Sciences and Medical Sciences 69 （ 4 ） 486 - 494 2014年

研究論文（学術雑誌）, 共著, ISSN 1079-5006

Background.Prevention of disability is a major challenge in aging populations; however, the extent to which physical independence can be maintained toward the limit of human life span remains to be determined.Methods.We examined the health and functional status of 642 centenarians: 207 younger centenarians (age: 100-104 years), 351 semi-supercentenarians (age: 105-109 years), and 84 supercentenarians (age: >110 years). All-cause mortality was followed by means of an annual telephone or mailed survey.Results.Age-specific disability patterns revealed that the older the age group, the higher the proportion of those manifesting independence in activities of daily living at any given age of entry. Multiple logistic regression analysis identified male gender and better cognitive function as consistent determinants of physical independence across all age categories. In a longitudinal analysis, better physical function was significantly associated with survival advantage until the age of 110. However, mortality beyond that age was predicted neither by functional status nor biomedical measurements, indicating alternative trajectories of mortality at the highest ages.Conclusions.These findings suggest that maintaining physical independence is a key feature of survival into extreme old age. Future studies illuminating genetic and environmental underpinnings of supercentenarians' phenotypes will provide invaluable opportunities not only to improve preventive strategies but also to test the central hypotheses of human aging. © The Author 2013.

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Glycosylated hemoglobin level is associated with hearing impairment in older Japanese

Michikawa Takehiro, Mizutari Kunio, Saito Hideyuki, Takebayashi Toru, Nishiwaki Yuji

Journal of the American Geriatrics Society 62 （ 7 ） 1231 - 1237 2014年

研究論文（学術雑誌）, 共著, ISSN 0002-8614

Objectives To examine the association between glycemic levels (glycosylated hemoglobin (HbA_1c)) and hearing impairment in a general older population. Design Community-based prospective longitudinal cohort study. Setting Kurabuchi Town, Gunma Prefecture, Japan. Participants Residents (N = 831; 350 men, 481 women) aged 65 and older were examined in 2005 and 2006 and analyzed in a cross-sectional study. Residents without hearing impairment at baseline who participated in audiometric re-examinations 4 years later were analyzed (n = 338). Measurements Hearing impairment was defined as failure to hear a 30-dB signal at 1 kHz and a 40-dB signal at 4 kHz in the better ear in pure-tone audiometric tests. Results Mean HbA_1c level (National Glycohemoglobin Standardization Program) was 5.8 ± 0.8% (40 mmol/mol). Odds ratios (ORs) and 95% confidence intervals (CIs) of hearing impairment associated with HbA_1c were estimated using a logistic regression model. In the cross-sectional analysis, HbA_1c levels were positively associated with hearing impairment (OR per 1.0% increase in HbA_1c = 1.30, 95% CI = 1.00-1.68). This association persisted even after excluding 58 participants with a self-reported history of diagnosed diabetes mellitus. Longitudinal analysis revealed the temporality of the discussed association (OR = 1.52, 95% CI = 1.03-2.23). Conclusion The present study provides supportive evidence for a causal link between hyperglycemia and age-related hearing loss. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

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How and why did a regional palliative care program lead to changes in a region? A qualitative analysis of the Japan OPTIM study

Imura Chizuru, Morita Tatsuya, Kato Masashi, Akizuki Nobuya, Kinoshita Hiroya, Shirahige Yutaka, Suzuki Satoshi, Takebayashi Toru, Yoshihara Ritsuko, Eguchi Kenji

Journal of Pain and Symptom Management 47 （ 5 ） 849 - 859 2014年

研究論文（学術雑誌）, 共著, ISSN 0885-3924

Context Improving palliative care is one of the major issues throughout the world. Objectives The primary aim of this study was to explore how and why a regional palliative care program led to changes in a region. Methods As part of a nationwide mixed-methods study of a regional palliative care program, a qualitative study was performed with 101 health care professionals involved in the implementation of the program. In-depth interviews were done, focusing on perceived changes and the perceived reasons for the changes. We used thematic analyses. Results Seven themes were identified as follows: 1) improved communication and cooperation among regional health care professionals; 2) increased confidence in the system to care for cancer patients at home; 3) improved knowledge/skills, practice, and perception of palliative care; 4) contribution to self-growth; 5) wide variability in perceived changes in the knowledge and perception of patients, family members, and the general public; 6) wide variability in the perceived regionwide effects of the project; and 7) unresolved issues. Participants emphasized improved communication and cooperation among regional health care professionals and stated a variety of ways of how communication and cooperation influenced daily practice. The main reasons for changes included regionwide interdisciplinary conferences and informal interactions at a variety of meetings. Conclusion This study advances understanding of how the regional palliative care program created a change in the region. The findings are useful for developing a conceptual framework and identifying key interventions to improve regional palliative care for clinicians, researchers, and policy makers. © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

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[Work environment measurements of nanoparticles in the nanoparticle-handling-process using portable type particle sizer spectrometers].

Iwasawa Satoko, Tanaka Shigeru, Miyauchi Hiroyuki, Minozoe Aoi, Nakaza Masahiro, Takebayashi Toru

Sangyō eiseigaku zasshi = Journal of occupational health 55 （ 6 ） 269 - 272 2013年12月

研究論文（学術雑誌）, 共著, ISSN 1341-0725

Higher serum dehydroepiandrosterone sulfate levels are protectively associated with depressive symptoms in men, but not in women

Michikawa Takehiro, Nishiwaki Yuji, Nakano Makiko, Iwasawa Satoko, Yamada Mutsuko, Asakura Keiko, Yoshioka Noriyuki, Kuwahara Erika, Takebayashi Toru

American Journal of Geriatric Psychiatry 21 （ 11 ） 1154 - 1163 2013年11月

研究論文（学術雑誌）, 共著, ISSN 1064-7481

Objective: Dehydroepiandrosterone sulfate (DHEAS) appears to have a protective effect against depression, but evidence from prospective cohort studies is sparse. Therefore, weexamined the associationbetweenserumDHEAS levelsand depressive symptoms in older community-dwelling Japanese. Design: A community-based cohort study. Setting: Kurabuchi Town, Gunma Prefecture, Japan. Participants: A total of 554 residents (248 men and 306 women) age 65 years or older without depressive symptoms at baseline. Measurements: We performed a baseline examination of the subjects between 2005 and 2006 to determine serum DHEAS levels. The subjects were categorized into three groups based on age strata- and sex-specific tertiles of DHEAS. Depressive symptoms were assessed with the Geriatric Depression Scale 15-item version (GDS-15) in face-to-face home visit interviews carried out once in 2007 and once in 2008. The association of DHEAS with depressive symptoms (GDS-15 ≥ 6) was analyzed with the use of logistic regression models. Results: The incidence of depressive symptoms was 12.1% in men and 19.6% in women. In men, the multiadjusted odds ratio of depressive symptoms was 0.24 (95% confidence interval: 0.06-0.94, Wald χ₂ = 4.20, degrees of freedom = 1, p = 0.04) for the highest tertile compared with the lowest. The association observed for the highest versus the lowest remained significant even after adjustment for physical performance and cognitive function. In women, DHEAS was not associated with depressive symptoms. Conclusions: In this study, higher serum DHEAS levels were found to be protectively and independently associated with the risk of developing depressive symptoms in men, but not in women. © 2013 American Association for Geriatric Psychiatry.

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Age-Related Hearing Loss and the Factors Determining Continued Usage of Hearing Aids among Elderly Community-Dwelling Residents

Mizutari Kunio, Michikawa Takehiro, Saito Hideyuki, Okamoto Yasuhide, Enomoto Chieko, Takebayashi Toru, Ogawa Kaoru, Nishiwaki Yuji

PLoS ONE 8 （ 9 ） 2013年09月

研究論文（学術雑誌）, 共著

While hearing aids are recommended for people with age-related hearing loss, many with impaired hearing do not use them. In this study, we investigated how many elderly people in the study area needed hearing aids, and the factors that determined continued wearing of the devices. The study area was Kurabuchi Town, Japan, where 1,437 residents (those aged 65 years or over) were eligible for participation in the study; 1,414 participated, of whom, 103 (7.3%) were already using hearing aids at the start of the study. After the primary screening, hearing aids were lent to 68 participants (4.8%) who did not already have one, 38 of whom (60.3% of the borrowers, representing 2.7% of the total aged population) went on to wear the hearing aid continuously. The Hearing Handicap Inventory for the Elderly (HHIE) score was significantly elevated among these 38 participants. This study indicated that hearing aids are of potential benefit to many local residents. Multivariate logistic regression revealed that HHIE scores were associated with the extent of HA usage. The adjusted odds ratio for a 1-unit increase in HHIE score was 1.08 (95% confidence interval: 1.02-1.14). Programs like this, in which people with impaired hearing are identified at the local level and given appropriate assistance, are useful models for future use in societies with aging populations. © 2013 Mizutari et al.

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Identification of microRNAs differentially expressed between lung squamous cell carcinoma and lung adenocarcinoma

Hamamoto Junko, Soejima Kenzo, Yoda Satoshi, Naoki Katsuhiko, Nakayama Sohei, Satomi Ryosuke, Terai Hideki, Ikemura Shinnosuke, Sato Takashi, Yasuda Hiroyuki, Hayashi Yuichiro, Sakamoto Michiie, Takebayashi Toru, Betsuyaku Tomoko

Molecular Medicine Reports 8 （ 2 ） 456 - 462 2013年08月

研究論文（学術雑誌）, 共著, ISSN 1791-2997

Recent advances in the treatment of non-small cell lung cancer (NSCLC) with new agents require accurate histological subtyping at diagnosis to avoid the higher risk of an adverse response and to obtain the maximum therapeutic response. However, interobserver variability, tumor heterogeneity and the degree of differentiation may affect the decision concerning a pathological diagnosis of NSCLC. Therefore, the aim of this study was to identify specific microRNAs (miRNAs) as standardized biomarkers with high sensitivity and specificity in order to distinguish between squamous cell carcinoma (SCC) and adenocarcinoma (AC). Quantitative polymerase chain reaction (qPCR)-based miRNA array analysis was performed to identify microRNAs differentially expressed between SCC and AC using 86 resected NSCLC samples in addition to adjacent normal tissues. The results were confirmed by independent qRT-PCR assays with the same test samples and 88 additional validation samples, and from this we evaluated the usefulness of the identified miRNAs as biomarkers to distinguish between SCC and AC. Three miRNAs (hsa-miR-196b, hsa-miR-205 and hsa-miR-375) were identified. Discriminant analysis combining the three miRNAs appeared to distinguish SCC from AC accurately in the test and validation samples, demonstrating a sensitivity and specificity of 76 and 80%, and 85 and 83%, respectively. hsa-miR-196b, hsa-miR-205 and hsa-miR-375 were identified as biomarkers capable of distinguishing between lung SCC and lung AC. These newly identified miRNAs may prove to be highly valuable molecular markers for the classification of NSCLC histological subtypes and may contribute to the pathogenesis of each subtype of NSCLC.

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Spinal posture in the sagittal plane is associated with future dependence in activities of daily living

Kamitani Kojiro, Michikawa Takehiro, Iwasawa Satoko, Eto Norihito, Tanaka Taichiro, Takebayashi Toru, Nishiwaki Yuji

Journals of Gerontology - Series A Biological Sciences and Medical Sciences 68 （ 7 ） 869 - 875 2013年07月

研究論文（学術雑誌）, 共著, ISSN 1079-5006

Background. Accumulated evidence shows how important spinal posture is for aged populations in maintaining independence in everyday life. However, the cross-sectional designs of most previous studies prevent elucidation of the relationship between spinal posture and future dependence in activities of daily living (ADL). We tried to clarify the association by measuring spinal posture noninvasively in a community-based prospective cohort study of older adults, paying particular attention to thoracic curvature, lumbar curvature, sacral hip angle, and inclination to determine which parameter is most strongly associated with dependence in ADL.Methods. Spinal posture was evaluated in 804 participants (338 men, 466 women, age range: 65-94 years) who were independent in ADL at baseline. We defined dependence in ADL as admission to a nursing home or need of home assistance. During the 4.5-year follow-up period, 126 (15.7%) participants became dependent in ADL. The relationship between the spinal posture parameters and outcome was assessed by dividing the participants into sex-specific quartiles of the parameters.Results. Only inclination (angle subtended between the vertical and a line joining C7 to the sacrum) was associated with outcome, although lumbar curvature also showed a marginal association. The age- and sex-adjusted odds ratio for a 1 unit increase in the quartiles of inclination was 1.79 (confidence interval: 1.44, 2.23). After mutual adjustment for the 4 parameters, statistical significance for inclination still remained, with no substantial changes in the association estimates.Conclusions. This study indicates that spinal inclination is associated with future dependence in ADL among older adults. © 2013 © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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Beta-3-adrenergic receptor Trp64Arg polymorphism

Nakashima Hiroshi, Omae Kazuyuki, Nomiyama Tetsuo, Yamano Yuko, Takebayashi Toru, Sakurai Yutaka

Environmental Health and Preventive Medicine 18 （ 4 ） 323 - 329 2013年07月

研究論文（学術雑誌）, 共著, ISSN 1342-078X

Objectives: The Trp64Arg polymorphism of the beta-3-adrenergic receptor gene has been studied as a potential genetic factor contributing to the development of obesity. Several studies have investigated whether or not this polymorphism affects weight reduction due to exercise, but the results of these studies have not been consistent. Moreover, information on a population characterized by a wide ranges of physical activities is scarce. Thus, to further understand the impact of this polymorphism, we examined whether the polymorphism modulates the relationship between physical activity due to exercise (PAE) and percentage of body fat (%BF). Methods: The study population was 70 Japanese male young adults with a high prevalence of habitual exercise. PAE was estimated by a questionnaire, and %BF was measured by bioelectrical impedance analysis. Genotyping was done by PCR-restriction fragment length polymorphism analysis. Results: The median PAE value of the subjects was 6.9 MET-h/day with an interquartile range of 1.5-10.3 MET-h/day. PAE correlated significantly with %BF in the entire population and within the two subpopulations, namely, carriers or non-carriers of the Arg allele. Multiple regression analysis of PAE, Trp64Arg polymorphism, and the interaction term revealed that while the PAE-derived independent variable was statistically significant, the interaction term was insignificant. When the two regression lines of subjects with and without the Arg allele were considered, the difference between the two slopes did not deviate from zero, nor did the vertical distance of the two regression lines. These findings suggest that the impact of this polymorphism is limited. Conclusions: In our study population of young adult Japanese males, the impact of the Trp64Arg polymorphism on the association between exercise and body composition was weak, if it existed at all. © 2013 The Japanese Society for Hygiene.

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Incidence and characteristics of the 2009 influenza (H1N1) infections in inflammatory bowel disease patients

Naganuma Makoto, Fujii Toshimitsu, Kunisaki Reiko, Yoshimura Naoki, Takazoe Masakazu, Takeuchi Yoshiaki, Saito Eiko, Nagahori Masakazu, Asakura Keiko, Takebayashi Toru, Watanabe Mamoru

Journal of Crohn's and Colitis 7 （ 4 ） 308 - 313 2013年05月

研究論文（学術雑誌）, 共著, ISSN 1873-9946

Background: In 2009, influenza A (H1N1) infections spread worldwide. Because the use of immunomodulators is associated with an increased risk of infection, inflammatory bowel disease (IBD) patients who are on immunomodulators might be concerned about H1N1 influenza infections. The aim of this study was to investigate the age distribution and risk factors associated with H1N1 influenza of IBD patients in 2009-2010. Methods: A multicenter, prospective study was conducted, and 570 IBD patients were enrolled. Patients were followed up for 10. months to identify any new infections. The incidence and age distribution of the H1N1 influenza infections were analyzed. IBD patients with H1N1 influenza infections and 2 matched, noninfected IBD patients were selected to assess the effect of specifying the medication on the incidence of infections. Results: A total of 38 patients (6.7%) developed H1N1 influenza infections. The incidence of H1N1 influenza infections in patients aged less than 20. years was significantly higher than that among patients in other age groups (p < 0.01). The age distribution for H1N1 influenza infections in IBD patients was comparable to those in the general population. No patients needed hospitalization due to influenza infection. A total of 29 patients (76%) recovered from the H1N1 influenza symptoms within 7. days and 20 patients (53%) received antiviral treatment. The percentage of patients who used steroids or thiopurine was comparable between the cases of H1N1 influenza infection and the control group. Conclusion: Our prospective study showed that younger IBD patients were frequently infected with the influenza A (H1N1) virus as well as general population. Admission and fatal cases due to H1N1 influenza infections were not observed. © 2012 European Crohn's and Colitis Organisation.

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Biliary Findings Assist in Predicting Enlargement of Intraductal Papillary Mucinous Neoplasms of the Pancreas

Matsuzaki Juntaro, Suzuki Hidekazu, Okuda Shigeo, Tanimoto Akihiro, Asakura Keiko, Fukuhara Seiichiro, Okada Sawako, Hirata Kenro, Mori Hideki, Masaoka Tatsuhiro, Higuchi Hajime, Hozawa Shigenari, Kuribayashi Sachio, Takebayashi Toru, Hibi Toshifumi

Clinical Gastroenterology and Hepatology 11 （ 5 ） 548 - 554 2013年05月

研究論文（学術雑誌）, 共著, ISSN 1542-3565

Background & Aims: There is controversy over the optimal management strategy for patients with branch-duct type intraductal papillary mucinous neoplasms of the pancreas (BD-IPMNs), precursors to pancreatic cancer. We aimed to identify factors associated with the presence of BD-IPMNs and changes in their diameter. Methods: Two separate analyses were conducted in a cohort of patients who underwent magnetic resonance cholangiopancreatography (MRCP) in a single year (2006). MRCP findings and clinical outcomes of these patients were followed for a maximum of 6 years. We evaluated initial MRCP findings and demographics associated with the presence of BD-IPMNs at baseline and increase in BD-IPMN diameter over time. Results: During the follow-up period, 154 patients developed BD-IPMN and 322 patients did not. Older age, diabetes mellitus, gallbladder adenomyomatosis, and absence of gallstones were associated with the presence of BD-IPMNs at baseline. Increases in diameter of BD-IPMNs were associated with 3 baseline factors: BD-IPMN diameter greater than 17 mm, gallbladder adenomyomatosis, and a common bile duct diameter less than 5.5 mm. Patients with BD-IPMNs could be stratified into 4 groups with varying risk for the enlargement of BD-IPMNs over time: those with 3 risk factors (hazard ratio [HR], 11.4; 95% confidence interval [CI], 3.4-37.8), 2 risk factors (HR, 4.7; 95% CI, 1.7-12.8), or 1 risk factor (HR, 3.1; 95% CI, 1.2-8.2) compared with those without risk factors. Conclusions: For patients with BD-IPMNs, careful follow-up evaluation is particularly important for those with BD-IPMN >17 mm in size, common bile duct diameter <5.5 mm, or gallbladder adenomyomatosis. © 2013 AGA Institute.

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Tinnitus preceded depressive symptoms in community-dwelling older Japanese: A prospective cohort study

Michikawa, Takehiro, Nishiwaki, Yuji, Saito, Hideyuki, Mizutari, Kunio, Takebayashi, Toru

PREVENTIVE MEDICINE 56 （ 5 ） 333 - 336 2013年05月

研究論文（学術雑誌）, ISSN 0091-7435

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Long-term exposure to particulate matter in relation to mortality and incidence of cardiovascular disease

Nishiwaki Yuji, Michikawa Takehiro, Takebayashi Toru, Nitta Hiroshi, Iso Hiroyasu, Inoue Manami, Tsugane Shoichiro

Journal of Atherosclerosis and Thrombosis 20 （ 3 ） 296 - 309 2013年03月

研究論文（学術雑誌）, 共著, ISSN 1340-3478

Aim: Associations between long-term exposure to particulate matter (PM) and increased cardiovascular mortality have been reported, but few studies have investigated the associated incidence of cardiovascular disease, and none involved men. Methods: We used data on 78,057 participants (37,121 men, 40,936 women) to examine the associations of long-term exposure to PM with mortality and the incidence of cardiovascular diseases. Average PM levels in the relevant area during the study period were used as an index of individual exposure to each subject. Cox models adjusted for age, sex, smoking, environmental smoking, body mass index, and alcohol consumption were used, with further adjustments for nitrogen dioxide and sulfur dioxide exposure, systolic blood pressure, total cholesterol, and diabetes mellitus. Results: Increased PM levels were associated with an increased risk of incident coronary heart disease (CHD) and myocardial infarction (MI), particularly among smokers (adjusted hazard ratio (HR) per 10 μg/m³ increase in PM for CHD: 1.39, 95% confidence interval (CI) 1.01-1.93; for MI: 1.52, 1.08-2.13) and among women (for CHD: 1.63, 0.91-2.92; for MI: 1.99, 1.07-3.70); however, the observed positive association of PM exposure with the incidence of CHD and MI was not robust, and the association disappeared when one of the areas (Akita) was excluded. The association with CHD mortality was not statistically significant (adjusted HR per 10 μg/m³ increase in PM: 1.11, 0.92-1.33). There was an inverse association of long-term PM exposure with stroke mortality and incidence. There was no clear association between PM levels and lung cancer mortality and incidence. Conclusions: Long-term exposure to PM might increase the risk of incident CHD in middle-aged Japanese men and women. Our findings also suggest that women and smokers are especially vulnerable to PM exposure.

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Sunlight exposure may be a risk factor of hearing impairment

Michikawa Takehiro, Nishiwaki Yuji, Asakura Keiko, Hillebrand Greg, Miyamoto Kukizo, Ono Masaji, Kinjo Yoshihide, Akiba Suminori, Takebayashi Toru

Journals of Gerontology - Series A Biological Sciences and Medical Sciences 68 （ 1 ） 96 - 103 2013年01月

研究論文（学術雑誌）, 共著, ISSN 1079-5006

Background.Oxidative stress is an important factor in the pathology of age-related hearing loss. Recent animal studies have reported that ultraviolet radiation in sunlight is related to systemic induction of oxidative stress. Chronic sun exposure leads to photodamaged skin, which is manifested as facial skin wrinkling and hyperpigmentation. We hypothesized that sunlight exposure, as assessed by the severity of facial skin photodamage, might be associated with hearing impairment through an oxidative stress mechanism. To examine this, we performed a cross-sectional analysis by using the baseline data from a community-based cohort study of older Japanese.Methods.A total of 805 residents (342 men and 463 women) aged 65 years or older living in Kurabuchi Town, Gunma prefecture, Japan, were examined between 2005 and 2006. Facial skin condition was quantified by image analysis of standardized facial images. Hearing impairment was defined as a failure to hear a 30-dB signal at 1 kHz and a 40-dB signal at 4 kHz in the better ear in pure-tone audiometric tests.Results.In men, facial wrinkle was positively associated with hearing impairment (for highest vs lowest: multivariate-adjusted odds ratio, 2.16; 95% confidence interval, 1.00-4.66; p for trend =. 01). Stratified analysis by age, educational level, smoking status, sunscreen or foundation use, and diabetes showed results similar to those for men as a whole. This association was particularly pronounced in men with the low levels of antioxidants and without occupational noise exposure. We observed no apparent association in women.Conclusions.The results support the hypothesis that chronic sun exposure is a risk factor of hearing impairment. © 2012 The Author.

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Reply to the letter by A. M. Bianco et al. regarding "effects of family history on IBD characteristics in Japanese patients"

Kuwahara Erika, Asakura Keiko, Nishiwaki Yuji, Inoue Nagamu, Watanabe Mamoru, Hibi Toshifumi, Takebayashi Toru

Journal of Gastroenterology 48 （ 1 ） 145 - 146 2013年01月

研究論文（学術雑誌）, 共著, ISSN 0944-1174

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[Comparison of data between intratracheal instillation and inhalation studies for estimation of harmful effects of manufactured nanomaterials].

Morimoto Yasuo, Horie Masanori, Kitajima Schinichi, Fukushima Shoji, Takebayashi Toru

Nihon eiseigaku zasshi. Japanese journal of hygiene 68 （ 3 ） 161 - 167 2013年

研究論文（学術雑誌）, 共著, ISSN 0021-5082

We reviewed the difference in data between the inhalation and intratracheal instillation studies of inhaled materials and how to diminish the difference in data between the two studies in order to examine the usefulness of intratracheal instillation study for the estimation of the harmful effects of manufactured nanomaterials. The differences in the data of the intratracheal instillation study from those of the inhalation study, which is the gold standard, are as follows: 1) artificial effect of the bolus, 2) nonuniformity of lung distribution of materials, 3) no threshold of clearance, 4) low deposition level of materials in the brain and neonates, and 5) the effect of dispersant on the lung. We consider that the approaches to diminishing the difference in data between the two studies are as follows: 1) maintain the dispersion of nanomaterials, 2) avoid the overdosing of nanomaterials, and 3) maintain a low concentration of the dispersant in the intratracheal instillation study.

Long-Term Exposure to Particulate Matter in Relation to Mortality and Incidence of Cardiovascular Disease: The JPHC Study

武林　亨

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS 20 （ 3 ） 296 - 309 2013年

研究論文（学術雑誌）, ISSN 1340-3478

Pandemic influenza virus surveillance, Izu-Oshima Island, Japan

Inamasu Tomoko, Sudo Kouji, Kato Shingo, Deguchi Hiroshi, Ichikawa Manabu, Shimizu Tadanori, Maeda Tadami, Fujimoto Shuhei, Takebayashi Toru, Saito Tomoya

Emerging Infectious Diseases 18 （ 11 ） 1882 - 1885 2012年11月

研究論文（学術雑誌）, 共著, ISSN 1080-6040

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Higher serum dehydroepiandrosterone sulfate levels are protectively associated with depressive symptoms in men, but not in women

Michikawa Takehiro, Nishiwaki Yuji, Nakano Makiko, Iwasawa Satoko, Yamada Mutsuko, Asakura Keiko, Yoshioka Noriyuki, Kuwahara Erika, Takebayashi Toru

American Journal of Geriatric Psychiatry 2012年10月

研究論文（学術雑誌）, 共著, ISSN 1064-7481

OBJECTIVE: Dehydroepiandrosterone sulfate (DHEAS) appears to have a protective effect against depression, but evidence from prospective cohort studies is sparse. Therefore, we examined the association between serum DHEAS levels and depressive symptoms in older community-dwelling Japanese. DESIGN: A community-based cohort study. SETTING: Kurabuchi Town, Gunma Prefecture, Japan. PARTICIPANTS: A total of 554 residents (248 men and 306 women) age 65 years or older without depressive symptoms at baseline. MEASUREMENTS: We performed a baseline examination of the subjects between 2005 and 2006 to determine serum DHEAS levels. The subjects were categorized into three groups based on age strata- and sex-specific tertiles of DHEAS. Depressive symptoms were assessed with the Geriatric Depression Scale 15-item version (GDS-15) in face-to-face home visit interviews carried out once in 2007 and once in 2008. The association of DHEAS with depressive symptoms (GDS-15 ≥ 6) was analyzed with the use of logistic regression models. RESULTS: The incidence of depressive symptoms was 12.1% in men and 19.6% in women. In men, the multiadjusted odds ratio of depressive symptoms was 0.24 (95% confidence interval: 0.06-0.94, Wald χ = 4.20, degrees of freedom = 1, p = 0.04) for the highest tertile compared with the lowest. The association observed for the highest versus the lowest remained significant even after adjustment for physical performance and cognitive function. In women, DHEAS was not associated with depressive symptoms. CONCLUSIONS: In this study, higher serum DHEAS levels were found to be protectively and independently associated with the risk of developing depressive symptoms in men, but not in women.

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Effects of family history on inflammatory bowel disease characteristics in Japanese patients

Kuwahara Erika, Asakura Keiko, Nishiwaki Yuji, Inoue Nagamu, Watanabe Mamoru, Hibi Toshifumi, Takebayashi Toru

Journal of Gastroenterology 47 （ 9 ） 961 - 968 2012年09月

研究論文（学術雑誌）, 共著, ISSN 0944-1174

Background Although the prevalence of inflammatory bowel disease (IBD) is reported to have reached a plateau in Western countries, it is increasing in Asia. The etiology of IBD is still under investigation. We performed an epidemiological study to clarify the characteristics of IBD in Japan, focusing on patients' family history. Methods We obtained clinical data on ulcerative colitis (UC) (46,114 cases) and Crohn's disease (CD) (11,305 cases) in 2007 from an electronic database maintained under the Japanese Ministry of Health, Labour and Welfarés nationwide registry system, and analyzed the differences in disease characteristics between patients with IBD who had a family history of the disease and those who did not. Results A total of 2.7% of the patients with UC and 2.6% of those with CD had a family history. The present age and age at disease onset were lower among the patients with UC who had a family history than among those without (present age: p0.001; age at disease onset: p0.001; Mann-Whitney U-test), but no similar trend was observed in the patients with CD. Disease severity was worse among both the UC and CD patients with a family history. The clinical course of patients with UC was not affected by family history. Levels of independence in daily life were associated with family history among CD patients, whereas age was associated with levels of independence in daily life among UC patients. Conclusion Disease characteristics of IBD vary in some aspects according to the presence or absence of a family history. © 2012 Springer.

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Self-reported hearing loss in older adults is associated with future decline in instrumental activities of daily living but not in social participation

Yamada Mutsuko, Nishiwaki Yuji, Michikawa Takehiro, Takebayashi Toru

Journal of the American Geriatrics Society 60 （ 7 ） 1304 - 1309 2012年07月

研究論文（学術雑誌）, 共著, ISSN 0002-8614

Objectives To investigate whether self-reported hearing loss in older adults is associated with a decline in their ability to perform instrumental activities of daily living (IADL) or a decline in social participation. Design Prospective follow-up. Setting Community. Participants One thousand two hundred fifty-four adults aged 65 to 98. Measurements Self-reported hearing loss, IADL, and social participation were evaluated through home-visit surveys. Self-reported hearing loss was measured according to responses to the question, "Do you have difficulty hearing and understanding what a person says to you in a quiet room if they speak normally to you, even when wearing your hearing aid?" Levels of IADL and social participation were measured using the subscales of the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC). Results Of the 921 participants with a perfect baseline IADL score and valid follow-up scores, 105 also self-reported hearing loss at baseline. Of this group, 44.8% (total n = 105) reported a decline in their IADL score over the 3-year follow-up period. After adjusting for major confounders, a statistically significant difference in experiencing an IADL decline over the 3-year period was found between those with hearing loss at baseline and those without (odds ratio (OR) = 1.79, 95% confidence interval (CI) = 1.12-2.87). Self-reported hearing loss at baseline did not have a statistically significant effect on decline in social participation (OR = 1.05, 95% CI = 0.63-1.76) over the 3-year follow-up period. Conclusion Self-reported hearing loss was associated with a decline in IADL, but not with social participation. © 2012, The American Geriatrics Society.

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Knowledge, beliefs, and concerns about opioids, palliative care, and homecare of advanced cancer patients

Akiyama Miki, Takebayashi Toru, Morita Tatsuya, Miyashita Mitsunori, Hirai Kei, Matoba Motohiro, Akizuki Nobuya, Shirahige Yutaka, Yamagishi Akemi, Eguchi Kenji

Supportive Care in Cancer 20 （ 5 ） 923 - 931 2012年05月

研究論文（学術雑誌）, 共著, ISSN 0941-4355

Purpose Patients' knowledge, beliefs, or concerns about opioids, palliative care, and homecare can be potential barriers to providing quality palliative care. The primary aim of this study was to clarify knowledge about opioids, beliefs about palliative care, and concerns about homecare in advanced cancer patients. Methods An anonymous questionnaire was sent to 1,619 outpatients with advanced cancer at 25 hospitals in four different regions of Japan. The respondents were asked to report their knowledge about opioids, beliefs about palliative care, and concerns about homecare, in addition to the levels of their sense of security regarding receiving cancer care in the region. Results A total of 925 responses were received. In total, 28% believed that opioids are addictive and/or shorten life; 52% believed that palliative care is only for terminally ill patients; 75% agreed that being taken care of at home puts a heavy burden on the family; and 61% agreed that homevisit services cannot respond to sudden changes in a patient's condition. Levels of patients' sense of security were significantly higher in those who agreed that "opioids can relieve most pain caused by cancer" "palliative care relieves pain and distress", "palliative care is provided along with chemotherapy and/or radiation therapy", and "pain can be alleviated as effectively through home-visit services as it can at the hospital", and those who disagreed with the statements that "home-visit services cannot respond to sudden changes in a patient's condition" and "being taken care of at home puts a burden on the family". Conclusions Advanced cancer patients frequently had incorrect knowledge about opioids, a belief that palliative care is only for terminally ill patients, and concerns about homecare, especially the family burden and responses to sudden changes. Providing appropriate information about the safety of opioids, the availability of palliative care during the entire course of the disease, and realistic information about homecare is of marked importance to promote patients' sense of security. © Springer-Verlag 2011.

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Classification of functional dyspepsia based on concomitant bowel symptoms

Matsuzaki J., Suzuki H., Asakura K., Fukushima Y., Inadomi J. M., Takebayashi T., Hibi T.

Neurogastroenterology and Motility 24 （ 4 ） 2012年04月

研究論文（学術雑誌）, 共著, ISSN 1350-1925

Background Functional dyspepsia (FD) is a heterogeneous disease, and categorized into postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). However, many FD patients have overlap of both PDS and EPS. The present study was designed to examine whether FD could be categorized based on the presence of concomitant gastrointestinal symptoms. Methods A web survey comprised of the Gastrointestinal Symptom Rating Scale (GSRS), Rome III criteria of FD, and demographic information was sent to public participants who have no history of severe illness. Factor and cluster analyses were conducted to identify sub-categories of FD based on GSRS. Key Results A total of 8038 participants completed the survey. A total of 563 participants met the criteria for FD, whereas 6635 participants did not have dyspepsia symptoms. The remainder had either organic disease (377) or uninvestigated dyspepsia (463). The cluster analysis categorized participants as constipation predominant (cluster C), diarrhea predominant (cluster D), or having neither diarrhea nor constipation (cluster nCnD). Cluster C and D were significantly associated with the presence of FD [odds ratio (OR) 2.57, 95% confidence interval (CI) 2.06-3.21; OR 2.80; 95% CI 2.27-3.45, respectively]. In FD, especially in PDS cases, the scores of upper gastrointestinal symptoms were higher in cluster C or D than in cluster nCnD. Conclusions & Inferences The severity of dyspepsia symptoms is associated with the presence of bowel symptoms especially in PDS. This novel categorization of FD based on concomitant constipation or diarrhea may improve classification of patients. © 2012 Blackwell Publishing Ltd.

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Clinical trial coordination under the evaluation system of investigational medical care in Japan

Aotani Eriko, Hata Tomomi, Kawakami Atsuko, Tsuboi Sae, Numagami Nami, Ushitani Mayumi, Miyata Kaoru, Nonaka Miwa, Takeuchi Masahiro, Takebayashi Toru, Fujiwara Keiichi

Japanese Pharmacology and Therapeutics 40 （ SUPPL. 1 ） 2012年03月

研究論文（学術雑誌）, 共著, ISSN 0386-3603

The Evaluation System of Investigational Medical Care (ESIMeC) is a new clinical trial system that Ministry of Health, Labour and Welfare authorizes the coverage of medical expenses by Japanese health insurance system for the patients participating in the approved clinical trials with high quality control mechanism. This system became effective in 2008. The Kitasato University Clinical Trials Coordinating Center has supported two randomized, phase III trials being conducted under ESIMeC since 2009. One trial is to evaluate the efficacy and safety of intraperitoneal (IP) chemotherapy of Carboplatin for ovarian cancer patients ; another trial is to evaluate the efficacy and safety of new anticancer agent Bevacizumab for recurrent ovarian cancer patients. Carboplatin is approved for ovarian cancer by intravenous administration, but not for IP administration. Bevacizumab is not approved for ovarian cancer. However, the indication-directed trial has been completed for the first line chemotherapy for ovarian cancer, but not for the recurrent setting. In this article, we discuss the issues that need to be improved in the future, as well as the importance of the clinical trial coordinating center, so that ESIMeC will work better to accelerate investigator-initiated clinical trials evaluating new agents/medical techniques with no indication approval in Japan. Critical issues in cancer clinical trial coordination under ESIMeC include being familiar with the system itself, development of the clinical trial team, support of the application process for ESIMeC, establishment of serious adverse event reporting procedures, management of the study agents, and cost-effective study monitoring.

[Descriptive epidemiology of inflammatory bowel disease in Japan].

Takebayashi Toru

Nihon rinsho. Japanese journal of clinical medicine 70 Suppl 1 39 - 43 2012年02月

研究論文（学術雑誌）, 共著, ISSN 0047-1852

Maximum occlusal force and physical performance in the oldest old

Iinuma Toshimitsu, Arai Yasumichi, Fukumoto Motoko, Takayama Michiyo, Abe Yukiko, Asakura Keiko, Nishiwaki Yuji, Takebayashi Toru, Iwase Takashi, Komiyama Kazuo, Gionhaku Nobuhito, Hirose Nobuyoshi

Journal of the American Geriatrics Society 60 （ 1 ） 68 - 76 2012年01月

研究論文（学術雑誌）, 共著, ISSN 0002-8614

Objectives To elucidate the independent relationship between masticatory and physical performance in community-living oldest old people (mean age ± standard deviation 87.8 ± 2.2, range 85-102). Design Cross-sectional analysis. Setting University research center or home-based examination. Participants Four hundred eighty-nine community-living individuals (219 men, 270 women) aged 85 and older. Measurements Maximum occlusal force (MOF) was measured using an occlusal force measuring device. Sociodemographic and functional factors, oral health, comorbidities, blood chemistry, lower extremity performance, and handgrip strength were assessed. Blood chemistry analyses included serum albumin, C-reactive protein, interleukin (IL)-6, and total and free testosterone. Results MOF was significantly associated with age, body mass index, and cognitive impairment in men but not in women. Comorbidities and blood chemistry were not associated with MOF except for a significant association with IL-6 concentration in women. In a multivariate model adjusted for various confounders, lower MOF was associated with greater risk for poor performance on the timed up and go (TUG) test in men and women (men: odds ratio (OR)=2.34, 95% confidence interval (CI)=1.02-5.38; women: OR=2.44, 95% CI=1.12-5.33). MOF was similarly associated with performance in chair standing, one-leg standing, and handgrip strength only in men. These associations remained after adjustment for number of natural teeth. Conclusion MOF was strongly and independently associated with all measures of physical performance in men and with the TUG test in women after adjustment for various confounders, suggesting that age-related declines in masticatory and skeletal muscle functions share common mechanistic pathways in older age, particularly in men. © 2011, The American Geriatrics Society.

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Prevalence and risk factors of dry eye disease in Japan

Uchino Miki, Nishiwaki Yuji, Michikawa Takehiro, Shirakawa Kazuhiro, Kuwahara Erika, Yamada Mutsuko, Dogru Murat, Schaumberg Debra A., Kawakita Tetsuya, Takebayashi Toru, Tsubota Kazuo

Ophthalmology 118 （ 12 ） 2361 - 2367 2011年12月

研究論文（学術雑誌）, 共著, ISSN 0161-6420

Objective: To estimate the prevalence and risk factors of dry eye disease (DED) in a rural setting in Japan. Design: Cross-sectional study. Participants: We included 3294 subjects, aged <40 years who were in the residential registry for Koumi town. Intervention: Subjects in a rural mountain area, Koumi town, completed questionnaires designed to detect dry eye diagnosis and risk factors. Main Outcome Measures: Clinically diagnosed DED was defined as the presence of a previous clinical diagnosis of DED by ophthalmologists or severe symptoms of DED (both dryness and irritation constantly or often). Current symptoms of DED and possible risk factors such as age, gender, educational history, smoking history, alcohol drinking history, height and weight, visual display terminal (VDT) use, and contact lens (CL) wear, and past/current history of certain common systemic diseases were the main outcome measures. We used logistic regression analysis to examine associations between DED and other demographic factors. Results: Of the 3294 eligible residents, 2791 residents (85%) completed the questionnaire. The percentage of women with a composite outcome of clinically diagnosed DED or severe symptoms (21.6%; 95% confidence interval [CI], 19.523.9) was higher than that of men (12.5%; 95% CI, 10.714.5; P<0.001). A low body mass index (BMI; odds ratio [OR], 2.07; 95% CI, 0.984.39), CL use (OR, 3.84; 95% CI, 1.4610.10), and hypertension (HT) (OR, 1.39; 95% CI, 0.942.06) were risk factors for DED in men. Use of a VDT (OR, 2.33; 95% CI, 1.124.85), CL use (OR, 3.61; 95% CI, 2.136.10), and myocardial infarction or angina were the risk factors (OR, 2.64; 95% CI, 1.514.62), whereas high BMI was a preventive factor (OR, 0.69; 95% CI, 0.481.01) for DED in women. Conclusions: Among a Japanese cohort, DED leading to a clinical diagnosis or severe symptoms is prevalent. Use of CLs was a common dry eye risk factor in both genders. The condition is more prevalent in men with low BMI, HT, and in women with myocardial infarction or angina and VDT use. Relevant measures directed against the modifiable risks may provide a positive impact on public health and quality of life of Japanese. © 2011 by the American Academy of Ophthalmology.

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[Health service research (17) &quot;Industrial health and health service research&quot;].

Takebayashi Toru

[Nihon kōshū eisei zasshi] Japanese journal of public health 58 （ 12 ） 1056 - 1059 2011年12月

研究論文（学術雑誌）, 共著, ISSN 0546-1766

Prism adaptation therapy enhances rehabilitation of stroke patients with unilateral spatial neglect

Mizuno Katsuhiro, Tsuji Tetsuya, Takebayashi Toru, Fujiwara Toshiyuki, Hase Kimitaka, Liu Meigen

Neurorehabilitation and Neural Repair 25 （ 8 ） 711 - 720 2011年10月

研究論文（学術雑誌）, 共著, ISSN 1545-9683

Background and objective. Unilateral spatial neglect (USN) can interfere with rehabilitation processes and lead to poor functional outcome. The purpose of this study was to determine whether prism adaptation (PA) therapy improves USN and functional outcomes in stroke patients in the subacute stage. Methods. A multicenter, double-masked, randomized, controlled trial was conducted to evaluate the effects of a 2-week PA therapy on USN assessed with the Behavioral Inattention Test (BIT), the Catherine Bergego Scale (CBS), and activities of daily living (ADL) as evaluated with the Functional Independence Measure (FIM). A total of 38 USN patients with right-brain damage were divided into prism (n = 20) and control (n = 18) groups. Patients were divided into mild and severe USN groups according to BIT behavioral test (mild 55 and severe<55). The prism group performed repetitive pointing with prism glasses that induce rightward optical shift twice daily, 5 days per week, for 2 weeks, whereas the control group performed similar pointing training with neutral glasses. Results. The FIM improved significantly more in the prism group. In mild USN patients, there was significantly greater improvement of BIT and FIM in the prism group. Conclusions. PA therapy can significantly improve ADL in patients with subacute stroke. © 2011 American Society of Neurorehabilitation.

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Acoustic neuroma risk in relation to mobile telephone use: Results of the INTERPHONE international case-control study

武林　亨

CANCER EPIDEMIOLOGY 35 （ 5 ） 453 - 464 2011年10月

研究論文（学術雑誌）, ISSN 1877-7821

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Association of short sleep duration with impaired glucose tolerance or diabetes mellitus

Katano Sayuri, Nakamura Yasuyuki, Nakamura Aki, Murakami Yoshitaka, Tanaka Taichiro, Takebayashi Toru, Okayama Akira, Miura Katsuyuki, Okamura Tomonori, Ueshima Hirotsugu

Journal of Diabetes Investigation 2 （ 5 ） 366 - 372 2011年10月

研究論文（学術雑誌）, 共著, ISSN 2040-1116

Aims/Introduction: To examine the cross-sectional relationship between sleep duration and impaired glucose tolerance (IGT), including diabetes mellitus (DM), we analyzed a large-scale healthy workers database in Japan. Materials and Methods: We examined the baseline database of 4143 participants (3415 men and 728 women) aged 19-69years. Sleep duration of participants was categorized into four groups: <6, 6 to <7, 7 to <8 and ≥8h. The physical activity of each participant was classified according to the International Physical Activity Questionnaire (IPAQ). We defined IGT including DM (IGT/DM) in the present study according to previous studies as follows: fasting blood sugar level ≥110mg/dL, or if <8h after meals ≥140mg/dL, or on medication for diabetes mellitus, or those diagnosed as having DM. Logistic regression was applied to estimate the odds ratio (OR) to examine the relationship between IGT/DM, sleep duration and other related factors. Results: The number of participants with IGT/DM was 402 (9.7%). The factors that significantly associated with IGT/DM were age (OR 1.08, 95% confidence interval [CI] 1.07-1.10, P<0.001), high blood pressure (OR 1.94, CI 1.52-2.47, P<0.001), and <6h of sleep duration in comparison with 6 to <7h sleep (OR 2.32, CI 1.18-4.55, P=0.015). The associations of difficulty in sleep initiation, IPAQ classification, current smoking and alcohol intake with IGT/DM were not statistically significant. Conclusions: Our results showed that shorter sleep duration (<6h of sleep duration per night) was associated with a risk of IGT/DM independent of other lifestyle habits and metabolic risk factors. © 2011 Asian Association for the Study of Diabetes and Blackwell Publishing Asia Pty Ltd.

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Are you conscious of any age-related taste impairment? Prevalence of and factors associated with taste impairment in Japan

Michikawa Takehiro, Nishiwaki Yuji, Takebayashi Toru

Journal of the American Geriatrics Society 59 （ 5 ） 951 - 953 2011年05月

研究論文（学術雑誌）, 共著, ISSN 0002-8614

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Knee Pain and Future Self-Reliance in Older Adults: Evidence From a Community-Based 3-Year Cohort Study in Japan

TAKEBAYASHI TORU

JOURNAL OF EPIDEMIOLOGY 21 （ 3 ） 184 - 190 2011年05月

研究論文（学術雑誌）, ISSN 0917-5040

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Impact of hearing difficulty on dependence in activities of daily living (ADL) and mortality

Yamada Mutsuko, Nishiwaki Yuji, Michikawa Takehiro, Takebayashi Toru

Archives of Gerontology and Geriatrics 52 （ 3 ） 245 - 249 2011年05月

研究論文（学術雑誌）, 共著, ISSN 0167-4943

Studies have associated hearing impairment with adverse health outcomes, but the actual impact of hearing difficulty has been barely investigated. We investigated among older adults (i) the prevalence of hearing difficulty, (ii) the association of hearing difficulty with a composite outcome of dependence in activities of daily living (ADL) and death, and (iii) the population attributable risk fraction (PAF) of hearing difficulty. In 2005, a home-visit survey of 1364 Japanese older adults aged ≥65 (participation proportion = 95.5%) was conducted to evaluate self-reports of hearing difficulty. Over 3 years, 99.4% of the initial sample was followed. Outcomes were measured by incidence of death or dependence in ADL. In the sample, the prevalence of hearing difficulty was 17.7% (age ≥65) and 25.7% (age ≥75). Hearing difficulty at high levels was associated with a composite outcome of dependence in ADL and mortality (adjusted odds ratio = OR and 95% confidence interval = 95% CI = 6.19 (1.92-19.92)) as well as with each outcome independently. Improving the hearing difficulty from high to moderate or no difficulty would reduce the composite outcome in 4.3% (age ≥65) and in 6.3% (age ≥75) of the target population. In conclusion, hearing difficulty was common, was associated with and had substantial impact on adverse health outcomes. © 2010 Elsevier Ireland Ltd.

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Etiological difference between ultrashort- and short-segment Barrett's esophagus

Matsuzaki Juntaro, Suzuki Hidekazu, Asakura Keiko, Saito Yoshimasa, Hirata Kenro, Takebayashi Toru, Hibi Toshifumi

Journal of Gastroenterology 46 （ 3 ） 332 - 338 2011年03月

研究論文（学術雑誌）, 共著, ISSN 0944-1174

Background: Barrett's esophagus has been divided into three categories based on the extent of the metaplasia: long-segment (LSBE), short-segment (SSBE), and ultrashort-segment Barrett's esophagus (USBE). While both LSBE and SSBE are thought to be induced by gastroesophageal reflux, the etiology of USBE is still unclear. Methods: We conducted a case-control study to identify the differences in the pathogenesis between SSBE and USBE in a hospital-based population. The endoscopic findings and clinical factors of 199 patients with short-segment endoscopically suspected esophageal metaplasia (SS-ESEM) and 317 patients with ultrashort-segment ESEM (US-ESEM) were compared with those of 199 and 317 age- and gender-matched patients without ESEM. Results: The severity of gastric mucosal atrophy was marginally associated with the presence of US-ESEM [odds ratio (OR) 1.20, 95% confidence interval (CI) 0.98-1.46, p = 0.08], but not with that of SS-ESEM. On the other hand, the presence of gallstones and that of severe reflux esophagitis were associated with the presence of SS-ESEM (OR 2.19, 95% CI 1.21-3.98; OR 1.72, 95% CI 1.08-2.75), but not with that of US-ESEM. Presence of gastric corpus atrophy without gallstones was associated with the presence of US-ESEM, but not with that of SS-ESEM. Conclusions: Presence of gastric corpus atrophy was associated with an increased likelihood of the presence of US-ESEM, whereas the presence of gallstones was associated with an increased likelihood of the presence of SS-ESEM, suggesting difference in etiology between US- and SS-ESEM. © 2010 Springer.

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Body mass index misclassification due to kyphotic posture in Japanese community-dwelling adults aged 65 years and older

Nishiwaki Yuji, Michikawa Takehiro, Eto Norihito, Takebayashi Toru

Journals of Gerontology - Series A Biological Sciences and Medical Sciences 66 A （ 3 ） 326 - 331 2011年03月

研究論文（学術雑誌）, 共著, ISSN 1079-5006

Background: In older adults, kyphosis (slouching posture) can lead to underestimation of height, which may in turn lead to overestimation of body mass index (BMI). We investigated the extent to which inaccurate BMI assessments led to misclassification of elderly people as normal weight (when they were actually underweight) or overweight (actually normal weight). Methods: Anthropometric measurements were taken in 2005 and 2006 for 842 residents aged 65 years or older (women: 491; men: 351). We calculated BMI from measured height and weight (observed BMI) and then predicted BMI from height as determined by demi-span, which is unaffected by kyphosis (predicted BMI). Kyphosis was assessed by the number of blocks placed under the occiput required for the supine participant to achieve a neutral head position. Participants were classified as underweight (BMI < 18.5), normal weight, or overweight (BMI ≥ 25.0) according to both observed and predicted BMI; classification accordance was investigated by cross-tabulation. Results. Kyphosis was present in 17.2% of the participants overall and in 23.6% of those aged 75 years or older. Predicted BMI measurements showed that 11 % of participants with kyphosis requiring ≥ 3 blocks were misclassified as normal weight and that 10% were erroneously classified as overweight. In those aged 75 years or older, the corresponding figures were 15% and 12%. Conclusions. Our results suggest that inaccurate BMIs due to kyphosis lead to substantial numbers of older adults being misclassified as normal weight or overweight, which can cause significant distortions in data on the impact of underweight and overweight on health outcomes. © The Author 2011. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.

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[Epidemiologic review of long-term, low-level exposure to environmental chemicals and cardiovascular disease

Takebayashi Toru

Nihon eiseigaku zasshi. Japanese journal of hygiene 66 （ 1 ） 13 - 21 2011年01月

研究論文（学術雑誌）, 共著

The effects of exposure to environmental chemicals, such as heavy metals and fine particulates, on cardiovascular diseases have been reported. To set a permissible exposure standard, an exposure-response relationship should be elucidated. Thus, epidemiologic evidence in relation to long-term, low-level exposure to environmental chemicals (i.e., lead, cadmium, mercury, arsenic, PM(2.5), carbon disulfide) was reviewed. As a result, there exists a clear exposure-response relationship between exposure to lead or PM(2.5) and cardiovascular diseases, but those cohort studies were carried out in the US only. From epidemiologic viewpoint, "consistency" of the observed relationship must be clarified, especially findings of a study in the Japanese population. It is well known that the distribution pattern of cardiovascular risk factors are quite different between two countries, which could modify the true relationship. This will require studies of large samples from the general Japanese population with control for potential confouders. Moreover, to detect a small effect of exposure within low-level range, random misclassification of exposure as well as that of effect must be minimized. Thus, for studies of heavy metals, sensitive biomarkers identified in toxicological studies would be applied. For PM(2.5), a wide range of population samples should be covered by a national sampling network in the near future. Finally, the integration of epidemiologic and toxicological evidence would be more important for risk assessment of environmental chemicals at low exposure levels, because an exposure-response relationship from only epidemiologic observation may be unstable with a wide confidence interval around the threshold.

Target biopsy or step biopsy? Optimal surveillance for ulcerative colitis

Watanabe Toshiaki, Ajioka Yoichi, Matsumoto Takayuki, Tomotsugu Naoki, Takebayashi Toru, Inoue Eisuke, Iizuka Bunei, Igarashi Masahiro, Iwao Yasushi, Ohtsuka Kazuo, Kudo Shin Ei, Kobayashi Kiyonori, Sada Miwa, Matsumoto Takayuki, Hirata Ichiro, Murakami Kazunari, Nagahori Masakazu, Watanabe Kenji, Hida Nobuyuki, Ueno Fumiaki, Tanaka Shinji, Watanabe Mamoru, Hibi Toshifumi

Journal of Gastroenterology 46 （ SUPPL. 1 ） 11 - 16 2011年01月

研究論文（学術雑誌）, 共著, ISSN 0944-1174

Colorectal cancer is one of the complications of ulcerative colitis (UC) and the risk of cancer increases as the duration of the disease becomes longer. Surveillance colonoscopy has been considered to be important for the early detection and early treatment of colorectal cancer, especially in longstanding UC. Because it is not always easy to detect neoplastic lesions in UC endoscopically, guidelines recommend the use of step biopsy in surveillance, in which either 4 biopsy specimens for every 10 cm or a total of 33 or more biopsy specimens are obtained. However, it has been pointed out that a step biopsy obtaining several tens of biopsy specimens may not be an ideal method in terms of invasiveness to the patient or medical cost. Instead of step biopsy, recent studies report the usefulness of target biopsy, in which biopsy tissues are obtained only from regions suspected of neoplasia. Therefore, the Research Group for Intractable Inflammatory Bowel Disease of the Ministry of Health, Labour and Welfare of Japan has initiated a randomized controlled study to compare the efficacy of step biopsy and target biopsy. The present article gives an introduction to this ongoing randomized controlled trial in Japan. © 2010 Springer.

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[Treatment indications for sarcopenia: a systematic review of exercise intervention effect]

Miyachi Motohiko, Ando Daisuke, Oida Yukio, Oguma Yuko, Ono Rei, Kitabatake Yoshinori, Tanaka Kiyoji, Nishiwaki Yuji, Michikawa Takehiro, Yanagita Masahiko, Yoshimura Kimio, Takebayashi Tohru

Japanese Journal of Geriatrics 48 （ 1 ） 51 - 54 2011年

ISSN 0300-9173

Objective: To evaluate exercise intervention efficacy for the prevention and treatment of sarcopenia in the elderly. Methods: We conducted a systematic literature search of randomized controlled trials in the Physical Activity Guidelines Advisory Committee Report (before 2007), Pubmed, the Cochrane database, and Igaku Chuo Zasshi (January 2006 to August 2009) Data Extraction: Two authors independently extracted relevant data. A total of 951 articles were found by search engines, and 9 studies were finally selected after a review by 2 experts. The content of these studies, especially duration, sets, periods, frequency, and intensity of exercise intervention were extracted and summarized in a results table. Five of 6 articles concluded that high-intensity resistance training significantly increased soft lean tissue and muscle mass. The remaining 3 articles indicated that moderate-intensity resistance training did not affect soft lean tissue or muscle mass. Conclusion: This systematic review suggested that high-intensity resistance training with sufficient periods, frequency, repetitions, and sets is effective to counteract the loss of muscle mass associated with advancing age.

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Relationship between dietary and other lifestyle habits and cardiometabolic risk factors in men

Katano Sayuri, Nakamura Yasuyuki, Okuda Nagako, Murakami Yoshitaka, Chiba Nagako, Yoshita Katsushi, Tanaka Taichiro, Tamaki Junko, Takebayashi Toru, Okayama Akira, Miura Katsuyuki, Okamura Tomonori, Ueshima Hirotsugu

Diabetology and Metabolic Syndrome 3 （ 1 ） 2011年

研究論文（学術雑誌）, 共著

Background: Prevalence of men with cardiometabolic risk factors (CMRF) is increasing in Japan. Few studies have comprehensively examined the relation between lifestyles and CMRF. Methods. We examined the baseline data from 3,498 male workers ages 19 to 69 years who participated in the high-risk and population strategy for occupational health promotion (HIPOP-OHP) study at 12 large-scale companies throughout Japan. The physical activity of each participant was classified according to the International Physical Activity Questionnaire (IPAQ). Dietary intake was surveyed by a semi-quantitative Food Frequency Questionnaire. We defined four CMRF in this study as follows: 1) high blood pressure (BP): systolic BP 130 mmHg, or diastolic BP ≥85 mmHg, or the use of antihypertensive drugs; 2) dyslipidemia: high-density lipoprotein-cholesterol concentration < 40 mg/dl, or triglycerides concentration ≥150 mg/dl, or on medication for dyslipidemia; 3) impaired glucose tolerance: fasting blood sugar concentration ≥110 mg/dl; 4) obese: a body mass index ≥25 kg/m ². Results: Those who had 0 to 4 CMRF accounted for 1,597 (45.7%), 1,032 (29.5%), 587 (16.8%), 236 (6.7%), and 44 (1.3%) participants, respectively, in the Poisson distribution. Poisson regression analysis revealed that independent factors that contributed to the number of CMRF were age (b = 0.020, P < 0.01), IPAQ (b = -0.091, P < 0.01), alcohol intake (ml/day) (b = 0.001, P = 0.03), percentage of protein intake (b = 0.059, P = 0.01), and total energy intake (kcal)(b = 0.0001, P < 0.01). Furthermore, alcohol intake and its frequency had differential effects. Conclusions: Alcohol intake, percent protein and total energy intake were positively associated, whereas drinking frequency and IPAQ were inversely associated, with the number of CMRF. © 2011 Katano et al; licensee BioMed Central Ltd.

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Vitamin D deficiency and lifestyle factors in the oldest old

Sumiya Chieko, Arai Yasumichi, Takayama Michiyo, Abe Yukiko, Hirose Nobuyoshi, Asakura Keiko, Nishiwaki Yuji, Takebayashi Toru

Journal of the American Geriatrics Society 58 （ 11 ） 2242 - 2244 2010年11月

研究論文（学術雑誌）, 共著, ISSN 0002-8614

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Prevalence of metabolic syndrome is comparable between inflammatory bowel disease patients and the general population

Nagahori Masakazu, Hyun Sea Bong, Totsuka Teruji, Okamoto Ryuichi, Kuwahara Erika, Takebayashi Toru, Naganuma Makoto, Watanabe Mamoru

Journal of Gastroenterology 45 （ 10 ） 1008 - 1013 2010年10月

研究論文（学術雑誌）, 共著, ISSN 0944-1174

Background: Metabolic syndrome (MS) is associated with an increased risk of cardiovascular disease. However, its prevalence in inflammatory bowel disease (IBD) patients remains largely unknown. This study was planned to determine the prevalence of MS in Japanese IBD patients. Methods: The prevalence of MS among outpatients with IBD aged 18 or older was studied using the modified National Cholesterol Education Program Adult Treatment Panel III definition. Results: A total of 107 quiescent IBD patients, including 76 ulcerative colitis (UC) patients and 31 Crohn's disease (CD) patients, were studied. Sufficient data were collected from a total of 102 patients. Prevalence of MS was significantly higher in UC (23.0%) patients compared to CD patients (7.1%). MS prevalence was substantially higher among male IBD patients (21.1%) compared to female IBD patients (12.9%), particularly in patients over 30 years of age. No difference was observed in the prevalence of MS between our IBD cohort and the general population in both males and females aged 40 years and older (P = 0.707 in males, P = 0.328 in females). IBD patients with MS were also older than those without (50.2 ± 15.0 vs. 38.0 ± 11.9 years, P = 0.013). In a logistic regression analysis, age was the statistically significant predictor of MS among IBD patients. The odds ratio (95% confidence interval) was 1.064 (1.017-1.114). Conclusions: Prevalence of metabolic syndrome in our IBD patients was comparable to that of the general population. Because age was the independent risk factor for developing MS, evaluation for MS is needed for elderly IBD patients. © 2010 Springer.

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Inflammatory bowel disease in children

Ishige Takashi, Tomomasa Takeshi, Takebayashi Tohru, Asakura Keiko, Watanabe Mamoru, Suzuki Tomoko, Miyazawa Reiko, Arakawa Hirokazu

Journal of Gastroenterology 45 （ 9 ） 911 - 917 2010年09月

研究論文（学術雑誌）, 共著, ISSN 0944-1174

Objective: We analyzed the database of the Japanese nationwide inflammatory bowel disease (IBD) registry, which was started in 1975, to characterize basic epidemiological and clinical features of childhood IBD, comparing them to those in adults. Study design: We analyzed the age of disease onset, disease severity and anatomical distribution in patients that were newly registered between 2003 and 2006 (n = 2,940 for CD and 14,857 for UC). We also analyzed the current age, gender and family history of IBD of all patients filed in 2005, which included patients who were newly registered in 2005 and those who had been registered before 2005 and for whom an annual report had been received in 2005 (total number of subjects: 10,934 for CD and 37,846 for UC). Results: At the time of registration, 10.6% of CD and 5.9% of UC patients were ≤16 years old. In CD, the male to female ratio was 2.6 in adult- and 1.7 in childhood-onset patients (P < 0.001). In UC, the male to female ratio was close to 1 in both age groups. In comparison with adults, pediatric patients more commonly had a positive family history for CD and UC (P < 0.001), tended to have more severe disease at the time of registry (P < 0.001 for CD, P < 0.05 for UC) and more often had extensive colitis in UC (P < 0.001). Conclusion: The nationwide registry in Japan showed IBD in children has clinical features that are distinct from those in adults. © 2010 Springer.

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Relationship among physical activity, smoking, drinking and clustering of the metabolic syndrome diagnostic components

Katano Sayuri, Nakamura Yasuyuki, Nakamura Aki, Murakami Yoshitaka, Tanaka Taichiro, Nakagawa Hideaki, Takebayashi Toru, Yamato Hiroshi, Okayama Akira, Miura Katsuyuki, Okamura Tomonori, Ueshima Hirotsugu

Journal of Atherosclerosis and Thrombosis 17 （ 6 ） 644 - 650 2010年06月

研究論文（学術雑誌）, 共著, ISSN 1340-3478

Aim: To examine the relation between lifestyle and the number of metabolic syndrome (MetS) diagnostic components in a general population, and to find a means of preventing the development of MetS components. Methods: We examined baseline data from 3,365 participants (2,714 men and 651 women) aged 19 to 69 years who underwent a physical examination, lifestyle survey, and blood chemical examination. The physical activity of each participant was classified according to the International Physical Activity Questionnaire (IPAQ). We defined four components for MetS in this study as follows: 1) high BP: systolic BP ≥ 130 mmHg or diastolic BP ≥85 mmHg, or the use of antihypertensive drugs; 2) dyslipidemia: high-density lipoprotein-cholesterol concentration <40 mg/dL, triglycerides concentration ≥150 mg/dL, or on medication for dyslipidemia; 3) Impaired glucose tolerance: fasting blood sugar level ≥110 mg/d, or if less than 8 hours after meals ≥140 mg/dL), or on medication for diabetes mellitus; 4) obesity: body mass index ≥25 kg/m². Results: Those who had 0 to 4 MetS diagnostic components accounted for 1,726, 949, 484, 190, and 16 participants, respectively, in the Poisson distribution. Poisson regression analysis revealed that independent factors contributing to the number of MetS diagnostic components were being male (regression coefficient b = 0.600, p<0.01), age (b = 0.027, p<0.01), IPAQ class (b = -0.272, p = 0.03), and alcohol consumption (b = 0.020, p = 0.01). The contribution of current smoking was not statistically significant (b = -0.067, p = 0.76). Conclusion: Moderate physical activity was inversely associated with the number of MetS diagnostic components, whereas smoking was not associated.

Conception outcomes and opinions about pregnancy for men with inflammatory bowel disease

Sato Asaka, Naganuma Makoto, Asakura Keiko, Nishiwaki Yuji, Yajima Tomoharu, Hisamatsu Tadakazu, Iwao Yasushi, Takebayashi Toru, Watanabe Mamoru, Hibi Toshifumi

Journal of Crohn's and Colitis 4 （ 2 ） 183 - 188 2010年06月

研究論文（学術雑誌）, 共著, ISSN 1873-9946

Background and aims: Patients with inflammatory bowel disease (IBD) who want to have children are anxious to receive medical treatment. The consensus regarding pregnancy has not been surveyed for male IBD patients. The present study was investigated opinions among male IBD patients about pregnancy, conception and neonatal outcomes for partners. Methods: Subjects comprised 364 of 386 patients enrolled (94.3%). Subjects received a questionnaire regarding their opinions and thoughts about pregnancy. The course of partner's conceptions and presence of neonatal malformations was also surveyed. Results: The rate of live births for partners of male IBD patients was 91.6% (219/239). Most patients with CD (29/33; 88%) had their children after surgery had been performed. The rate of expressing hopes to have a child tended to be higher for patients with UC (93/128; 73%) than for patients with CD (61/97; 63%; p = 0.21). Furthermore, the rate of hesitation was significantly higher in CD patients (34/107; 32%) than in UC patients (38/188; 20%; p = 0.03).Patients considered that safety of medication (51%) and maintenance of remission (41%) was more important than receiving no treatment for IBD (19%) when planning to conceive. Mesalamine and infliximab were more favorable at conception than sulfasalazine and immunomodulators. Conclusions: This is the first report to survey the thinking of male IBD patients regarding pregnancy. Most male IBD patients considered "maintaining remission" as important at conception. Our study provides important information for IBD patients and for the treating physician when planning to conceive. © 2009 European Crohn's and Colitis Organisation.

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Brain tumour risk in relation to mobile telephone use: results of the INTERPHONE international case-control study

The INTERPHONE study group

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY 39 （ 3 ） 675 - 694 2010年06月

研究論文（学術雑誌）, ISSN 0300-5771

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Gallstones increase the prevalence of Barrett's esophagus

Matsuzaki Juntaro, Suzuki Hidekazu, Asakura Keiko, Saito Yoshimasa, Hirata Kenro, Takebayashi Toru, Hibi Toshifumi

Journal of Gastroenterology 45 （ 2 ） 171 - 178 2010年02月

研究論文（学術雑誌）, 共著, ISSN 0944-1174

Purpose: Bile and acid exposures are thought to be major risk factors for Barrett's esophagus in Western countries. The association of gallstones with Barrett's esophagus has not been fully evaluated. The present study was designed as a case-control study for determining the possible factors associated with endoscopically suspected esophageal metaplasia (ESEM), defined as an endoscopic finding suggestive of Barrett's esophagus, in Japanese patients. Methods: A total of 528 patients with ESEM were allocated to the case group, while 528 age- and gender-matched patients without ESEM were allocated to the control group. Findings on esophagogastroduodenoscopy and clinical background factors were compared using a multivariate logistic regression model. Results: The presence of gallstones and hiatus hernia and the severity of gastric mucosal atrophy were independently associated with the presence of ESEM [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.03-2.69; OR 2.75, 95% CI 1.75-4.33; OR 1.25, 95% CI 1.01-5.6, respectively]. Compared with subjects with neither gastric corpus atrophy nor gallstones, although subjects with gallstones alone were not associated with the presence of ESEM (OR 1.59, 95% CI 0.87-2.92), having both gastric corpus atrophy and gallstones was strongly associated with the presence of ESEM (OR 2.94, 95% CI 1.40-6.17). Conclusions: The presence of gallstones was independently associated with the presence of ESEM in the Japanese outpatient population, suggesting a causal association of distal esophageal bile exposure with the development of ESEM. Further studies are needed to confirm our findings in cases with histologically confirmed Barrett's esophagus. © 2009 Springer.

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Nine-month observation of effects of SO2 on the respiratory system in child Miyakejima citizens

Iwasawa Satoko, Michikawa Takehiro, Nakano Makiko, Nishiwaki Yuji, Tsuboi Tazuru, Tanaka Shigeru, Uemura Takamoto, Milojevic A., Nakashima Hiroshi, Takebayashi Toru, Morikawa Akihiro, Maruyama Kouichi, Kudo Shoji, Uchiyama Iwao, Omae Kazuyuki

[Nippon kōshū eisei zasshi] Japanese journal of public health 57 （ 1 ） 39 - 43 2010年01月

研究論文（学術雑誌）, 共著, ISSN 0546-1766

BACKGROUND: Mt. Oyama on Miyakejima Island erupted in June 2000 and all Miyake village citizens were forced to evacuate the island in the September, due to continuous eruptions and emission of unsafe amounts of volcanic gas, mainly sulfur dioxide (SO2). Beginning in February 2005, residents returned to live on the island despite the fact that volcanic gas was still being emitted. OBJECTIVE: To examine changes in the respiratory systems of included children from February 2006 to November 2006. METHODS: The study population was 141 children who participated in health checkups in November 2006, including 33 SO2 hypersusceptible children who had a current or past history of asthma, obstructive lung function, current symptoms of whistling and wheezing, and/or deterioration of respiratory symptoms. Respiratory effects were evaluated by a questionnaire for respiratory symptoms and by spirometry. SO2 was monitored at 7 sampling points within inhabited areas, and the mean SO2 concentration from February 2005 to November 2006 was 0.031 ppm. The area was categorized into four areas by average SO2 concentration, namely, areas L, H-1, H-2, and H-3, where the average SO2 levels were 0.019, 0.026, 0.032, and 0.045 ppm, respectively. RESULTS: Compared to children in area L, the frequencies of "phlegm" and "irritation of the nose" were significantly greater in the children in areas H-2 and H-3. %FVC and %FEV1 in hypersusceptible children were significantly reduced in November 2006 as compared to February 2006 (P = 0.047, 0.027), though no reduction observed in normosusceptible children. CONCLUSION: Respiratory functions in hypersusceptible Miyakejima children may be affected by SO2 exposure, and further follow-up observation is necessary.

Hearing Handicap Predicts the Development of Depressive Symptoms After 3 Years in Older Community-Dwelling Japanese

武林　亨

JOURNAL OF THE AMERICAN GERIATRICS SOCIETY 58 （ 1 ） 93 - 97 2010年01月

研究論文（学術雑誌）, ISSN 0002-8614

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Relation of gamma-glutamyltransferase and alcohol drinking with incident diabetes

Hozawa Atsushi, Okamura Tomonori, Tanaka Taichiro, Miura Katsuyuki, Kikuchi Yuriko, Kadowaki Takashi, Yoshita Katsushi, Takebayashi Toru, Tamaki Junko, Minai Junko, Tada Takayo, Chiba Nagako, Okayama Akira, Ueshima Hirotsugu

Journal of Atherosclerosis and Thrombosis 17 （ 2 ） 195 - 202 2010年

研究論文（学術雑誌）, 共著, ISSN 1340-3478

Aim: Gamma-glutamyltransferase (GGT) is known to correlate well with alcohol consumption; however, the relation between GGT and diabetes and that between alcohol consumption and diabetes mellitus (DM) is inconsistent. Thus, several questions, such as whether light to moderate drinkers can be considered as low risk for diabetes incidence irrespective of their GGT level, is unresolved. In this study, we investigated the relation of GGT or alcohol drinking with DM incidence considering the body mass index (BMI) in healthy Japanese workers. Methods: We followed 3095 men who did not have DM at baseline for 4 years. Incident diabetes was defined as a fasting (non-fasting) plasma glucose level of ≥7.0 (11.1) mmol/L, or treatment of diabetes. Multiple adjusted hazard ratios (HR) were calculated using Cox proportional models. Results: Participants with higher GGT (GGT ≥27 IU/L) showed an increased risk of diabetes incidence even when their BMI level was low. Although a U-shaped relation between alcohol drinking and incident diabetes was observed, the risk to light to moderate drinkers (alcohol <23 g/day) was not low if they were either overweight (BMI ≥25 kg/m2) or had higher GGT (HR= 2.60, p= 0.08) or both overweight and higher GGT (HR= 3.16, p= 0.07) compared with never drinkers without higher GGT and overweight. Conclusions: Higher GGT was associated with a higher incidence of DM irrespective of drinking status or obesity. Although a U-shaped relation between alcohol drinking and incident diabetes was observed, the risk to light to moderate drinkers was not low if they were either overweight or had higher GGT.

Prevalence and factors associated with tinnitus

Michikawa Takehiro, Nishiwaki Yuji, Kikuchi Yuriko, Saito Hideyuki, Mizutari Kunio, Okamoto Michiko, Takebayashi Toru

Journal of Epidemiology 20 （ 4 ） 271 - 276 2010年

研究論文（学術雑誌）, 共著, ISSN 0917-5040

Background: The prevalence of tinnitus is reported to be high in older Western populations, and several risk factors have been suggested. However, community-based evidence on prevalence is limited and, to our knowledge, there is no such information from older non-Western populations. The purpose of this study was to determine the prevalence and factors associated with tinnitus in community-dwelling Japanese elders. Methods: In this community-based cross-sectional study, 1320 residents of Kurabuchi Town aged 65 years or older (584 men and 736 women; participation proportion = 98.7%) were interviewed at home in 2006, and information on tinnitus and factors associated with tinnitus was collected. We estimated the prevalence of tinnitus by age group and sex and used a logistic regression model to investigate associated factors. Results: The prevalence of tinnitus was 18.6% (men: 18.0%; women: 19.0%); there were no statistically significant differences by age group or sex. Hearing difficulty, depressive mood, prescribed medication, past/current history of coronary heart disease, and knee joint pain requiring medical consultation were associated with tinnitus. Conclusions: These findings suggest that tinnitus is common in Japanese aged over 65 years. Because the factors associated with tinnitus in this cross-sectional study are potentially modifiable, they should be thoroughly investigated in a longitudinal study. © 2010 by the Japan Epidemiological Association.

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Iron intake does not significantly correlate with iron deficiency among young Japanese women

Asakura Keiko, Sasaki Satoshi, Murakami Kentaro, Takahashi Yoshiko, Uenishi Kazuhiro, Yamakawa Miki, Nishiwaki Yuji, Kikuchi Yuriko, Takebayashi Toru, Yamasaki Mitsuyo, Hisatomi Yuko, Soezima Junko, Takedomi Kazumi, Kohri Toshiyuki, Kaba Naoko, Uneoka Etsuko, Hayabuchi Hitomi, Umeki Yoko, Baba Keiko, Suzuki Maiko, Watanabe Reiko, Muramatsu Kanako, Ohki Kazuko, Shiga Seigo, Ebisawa Hidemichi, Fuwa Masako, Watanabe Tomoko, Suzuki Ayuho, Kudo Fumiyo, Shibata Katsumi, Fukuwatari Tsutomu, Hirose Junko, Takahashi Toru, Kato Masako, Goda Toshinao, Ichikawa Yoko, Suzuki Junko, Niida Yoko, Morohashi Satomi, Shimizu Chiaki, Takeuchi Naomi, Oka Jun, Ide Tomoko, Sugiyama Yoshiko, Furuki Mika

Public Health Nutrition 12 （ 9 ） 1373 - 1383 2009年09月

研究論文（学術雑誌）, 共著, ISSN 1368-9800

Objectives: We evaluated the association of nutrient intake with Fe deficiency with regard to lifestyle factors and health condition in young Japanese women. Uniquely among developed countries, dietary habits render Japanese populations vulnerable to Fe deficiency, owing to their relatively low intake of Fe and high intake of Fe absorption inhibitors, such as green tea and soyabeans. Design: A cross-sectional study. Setting and subjects: The subjects were 1019 female Japanese dietetic students aged 18-25 years. Dietary habits during the preceding month were assessed using a previously validated, self-administered, diet history questionnaire. Blood analysis was performed to assess body Fe status. Subjects were categorized with Fe deficiency when their serum ferritin levels were <12 ng/ml. Twenty-nine dietary variables, i.e. intakes of energy, sixteen nutrients including Fe and twelve food groups, were analysed using multivariate logistic regression models adjusted for possible confounders. Results: Of the subjects, 24.5 % were categorized with Fe deficiency. However, no dietary factors assessed were significantly associated with Fe deficiency. The risk of Fe deficiency was significantly lower in women with infrequent or no menstrual cycles than in those with regular cycles (OR = 0.58; 95 % CI 0.34, 1.00) and significantly higher in women with heavy menstrual flow than in women with average flow, albeit that these were self-reported (OR = 1.83; 95 % CI 1.35, 2.48). Conclusions: These results suggest that dietary habits, including Fe intake, do not significantly correlate with Fe deficiency among young Japanese women. © The Authors 2008.

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One-leg standing test for elderly populations

Michikawa Takehiro, Nishiwaki Yuji, Takebayashi Toru, Toyama Yoshiaki

Journal of Orthopaedic Science 14 （ 5 ） 675 - 685 2009年09月

研究論文（学術雑誌）, 共著, ISSN 0949-2658

Background: The one-leg standing (OLS) test is one of the balance tests used to diagnose musculoskeletal ambulation disability symptom complex (MARS), a condition newly defined by three professional Japanese medical societies in 2006 to help identify the symptoms of motor organ deterioration and establish preventive strategies. Although many studies have used the OLS test, none has shown conclusively that the test can be used as a practical marker of frailty among elderly people, especially in community settings. Based on the type of epidemiological study - i.e., descriptive epidemiology and analytical epidemiology (observational and intervention studies) - we reviewed evidence on three fundamental issues related to the OLS test: (1) testing procedures and reference values; (2) the associations between the OLS time and negative events; (3) improvement of the OLS time by intervention. These issues are key to any discussion of whether the OLS test can be used as a practical marker for predicting frailty in community-dwelling elderly populations. Methods: Articles were collected from MEDLINE databases using the search terms "one- leg standing" and the other names included in the same category. Results: Because various procedures are used to carry out the OLS test, the measured values for the OLS time varied widely from study to study. Some observational studies showed that the OLS time is related to negative events such as falls, declines in activity of daily living, and other morbidity. OLS times could be improved by several interventions. Conclusions: This review suggests that the OLS test can be a tool for predicting frailty in community-dwelling elderly populations. However, our review should be interpreted with caution because we did not confirm the evidence level of each of the studies we selected. Further research on this topic is needed. © 2009 The Japanese Orthopaedic Association.

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Trichloroethylene liver toxicity in mouse and rat

Sano Yuri, Nakashima Hiroshi, Yoshioka Noriyuki, Etho Norihito, Nomiyama Tetsuo, Nishiwaki Yuji, Takebayashi Toru, Oame Kazuyuki

Archives of Toxicology 83 （ 9 ） 835 - 849 2009年09月

研究論文（学術雑誌）, 共著, ISSN 0340-5761

Trichloroethylene (TCE), an industrial organic solvent found in the environment, is a known carcinogen in laboratory animals and is believed to be carcinogenic in humans. Its carcinogenicity is subject to species-specific differences in biological activity, causing hepatocellular carcinoma in mouse and renal-cell carcinoma in rat. We have sought to better understand TCE's mode of action (MOA) by studying the alterations in gene expression profiles of liver in mice and rats that were administrated TCE by oral gavage either once or daily for 14 days. Microarray analysis revealed distinct transcriptional profiles and differences in biological pathways not only species-specific, but also pulse-dose effects within each species. For example, inhibition of the TGF-β pathway and activation of MAPK signaling were specific to mice repeatedly exposed to TCE. A better understanding of the MOA in mice and rats will lead to better hypotheses of TCE's affect on humans. © 2009 Springer-Verlag.

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Lifestyle factors and visible skin aging in a population of Japanese elders

Asakura Keiko, Nishiwaki Yuji, Milojevic Ai, Michikawa Takehiro, Kikuchi Yuriko, Nakano Makiko, Iwasawa Satoko, Hillebrand Greg, Miyamoto Kukizo, Ono Masaji, Kinjo Yoshihide, Akiba Suminori, Takebayashi Toru

Journal of Epidemiology 19 （ 5 ） 251 - 259 2009年08月

研究論文（学術雑誌）, 共著, ISSN 0917-5040

Background: The number of studies that use objective and quantitative methods to evaluate facial skin aging in elderly people is extremely limited, especially in Japan. Therefore, in this cross-sectional study we attempted to characterize the condition of facial skin (hyperpigmentation, pores, texture, and wrinkling) in Japanese adults aged 65 years or older by using objective and quantitative imaging methods. In addition, we aimed to identify lifestyle factors significantly associated with these visible signs of aging. Methods: The study subjects were 802 community-dwelling Japanese men and women aged at least 65 years and living in the town of Kurabuchi (Takasaki City, Gunma Prefecture, Japan), a mountain community with a population of approximately 4800. The facial skin condition of subjects was assessed quantitatively using a standardized facial imaging system and subsequent computer image analysis. Lifestyle information was collected using a structured questionnaire. The association between skin condition and lifestyle factors was examined using multivariable regression analysis. Results: Among women, the mean values for facial texture, hyperpigmentation, and pores were generally lower than those among age-matched men. There was no significant difference between sexes in the severity of facial wrinkling. Older age was associated with worse skin condition among women only. After adjusting for age, smoking status and topical sun protection were significantly associated with skin condition among both men and women. Conclusions: Our study revealed significant differences between sexes in the severity of hyperpigmentation, texture, and pores, but not wrinkling. Smoking status and topical sun protection were significantly associated with signs of visible skin aging in this study population. © 2009 by the Japan Epidemiological Association.

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Serum Levels of Retinol and Other Antioxidants for Hearing Impairment Among Japanese Older Adults

武林　亨

JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES 64 （ 8 ） 910 - 915 2009年08月

研究論文（学術雑誌）, ISSN 1079-5006

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A cross-sectional observation of effect of exposure to N-Methyl-2- Pyrrolidone (NMP) on workers' health

Nishimura Shigeru, Yasui Hirohiko, Miyauchi Hiroyuki, Kikuchi Yuriko, Kondo Nami, Takebayashi Toru, Tanaka Shigeru, Mikoshiba Yuko, Omae Kazuyuki, Nomiyama Tetsuo

Industrial Health 47 （ 4 ） 355 - 362 2009年07月

研究論文（学術雑誌）, 共著, ISSN 0019-8366

This study was aimed at clarifying the effect of exposure to N-methyl-2-pyrrolidone (NMP) on workers' health. Fifteen male NMP-exposed workers and 15 referent male workers were recruited for this study. Exposure concentrations were assessed by determining NMP in the breathing zones and urinary NMP. Clinical examinations, motor and sensory nerve conduction velocities in the dominant arm, and neurobehavioral tests were carried out. The subjects were asked to complete self-administered questionnaires for subjective symptoms and psychological assessment. The mean NMP exposure concentrations ranged from 0.14 to 0.26 ppm, and urinary NMP levels at the end of each workday ranged from 0.17 to 0.22 mg/l, throughout the work week. In terms of clinical data, motor and sensory nerve conduction velocities, neurobehavioral tests, and subjective symptom assessments, there were no differences and no dose-dependent changes in either the means or the prevalence of abnormal findings between NMP-exposed and referent workers.

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Serum Antioxidants and Age-related Macular Degeneration among Older Japanese

Michikawa Takehiro, Ishida Susumu, Nishiwaki Yuji, Kikuchi Yuriko, Tsuboi Tazuru, Hosoda Kanae, Ishigami Ai, Iwasawa Satoko, Nakano Makiko, Takebayashi Toru

Asia Pacific Journal of Clinical Nutrition 18 （ 1 ） 1 - 7 2009年03月

ISSN 0964-7058

From the perspective of human nutrition, the prevention of age-related macular degeneration (AMD) through diet control is feasible and desirable. We investigated the relationship between serum antioxidants and AMD in the community-dwelling older Japanese eating a typical Japanese diet. In this study, 722 subjects aged 65 years or older (297 males and 425 females) who had gradable fundus photographs were included. The subjects were divided into three groups of early or late AMD or non-maculopathy. Serum antioxidants (alpha-, gammatocopherols, retinol, beta-cryptoxanthin, alpha-, beta-carotenes, lycopene, and lutein and zeaxanthin) were measured with high-performance liquid chromatography. To clarify the combined effect as the group of the antioxidants, we defined the carotene family (alpha-, beta-carotenes and lycopene) and carotenoid family (betacryptoxanthin, alpha-, beta-carotenes, lycopene, lutein and zeaxanthin). Tertiles of each serum antioxidant were obtained and the prevalence of early or late AMD was compared with univariate or multivariate analysis. The overall prevalence of early AMD was 4.4% (95% confidence interval: 3.1-6.2) and late AMD was 1.1% (0.5-2.2). Only alpha-tocopherol and beta-cryptoxanthin were related to late AMD as single antioxidants. On the other hand, the carotene and carotenoid families as a combination of antioxidants were protectively associated with late AMD. No relationship was found between serum antioxidants and early AMD. Our findings support the hypothesis that a combination of serum antioxidants obtained from the traditional Japanese diet is protective for late AMD, but not for early AMD.

Effects of SO₂ on respiratory system of adult miyakejima resident 2 years after returning to the Island

Iwasawa Satoko, Kikuchi Yuriko, Nishiwaki Yuji, Nakano Makiko, Michikawa Takehiro, Tsuboi Tazuru, Tanaka Shigeru, Uemura Takamoto, Ishigami Ai, Nakashima Hiroshi, Takebayashi Toru, Adachi Mitsuru, Morikawa Akihiro, Maruyama Kouichi, Kudo Shoji, Uchiyama Iwao, Omae Kazuyuki

Journal of Occupational Health 51 （ 1 ） 38 - 47 2009年01月

研究論文（学術雑誌）, 共著, ISSN 1341-9145

Background: Mt. Oyama in Miyakejima Island erupted in June, 2000. All Miyake villagers were forced to evacuate from the island in September, 2000, due to continuous eruptions and emissions of unsafe amounts of volcanic gas, mainly SO₂. From February, 2005, Miyake villagers returned to the island despite volcanic gas still being emitted. Objectives: This study examines the 2-yr changes in Miyake residents' respiratory systems from autumn 2004 to November 2006. Methods: The study population was 823 Miyake adult residents who participated in the health check-up in 2006. Respiratory effects were evaluated by a questionnaire for respiratory symptoms and spirometry. SO₂ has been continuously monitored at 7 sampling points of the inhabited area. The mean SO₂ concentration from February 2005 to November 2006 was 0.031 ppm. The area was categorized into 4 areas by SO₂ concentration, namely, areas L, H-1, H-2 and H-3, where average SO₂ concentrations were 0.019, 0.026, 0.032, and 0.045 ppm, respectively. Results: The study subjects showed no deterioration in lung function. Prevalence of cough and phlegm among all participants were significantly higher in 2006 than in 2004, and age-, sex- and smoking-adjusted odds ratios of cough and phlegm were 1.75 (95%CI 1.33- 2.30) and 1.44 (1.12-1.87). Prevalence of chronic bronchitis-like symptoms among normosusceptive subjects in 2006 was 4.1% which was significantly higher than that of 2.1% in 2004 (p=0.035). Compared to area L, the frequencies of phlegm and irritation of the nose were significantly increased in areas H-2 and H-3. Conclusion: SO₂ exposure-related respiratory symptoms were observed in adult Miyakejima residents after returning to the island.

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Gender-specific associations of vision and hearing impairments with adverse health outcomes in older Japanese

Michikawa Takehiro, Nishiwaki Yuji, Kikuchi Yuriko, Nakano Makiko, Iwasawa Satoko, Asakura Keiko, Milojevic Ai, Mizutari Kunio, Saito Hideyuki, Ishida Susumu, Okamura Tomonori, Takebayashi Toru

BMC Geriatrics 9 （ 1 ） 2009年

研究論文（学術雑誌）, 共著, ISSN 1471-2318

Background. Several epidemiological studies have shown that self-reported vision and hearing impairments are associated with adverse health outcomes (AHOs) in older populations; however, few studies have used objective sensory measurements or investigated the role of gender in this association. Therefore, we examined the association of vision and hearing impairments (as measured by objective methods) with AHOs (dependence in activities of daily living or death), and whether this association differed by gender. Methods. From 2005 to 2006, a total of 801 residents (337 men and 464 women) aged 65 years or older of Kurabuchi Town, Gunma, Japan, participated in a baseline examination that included vision and hearing assessments; they were followed up through September 2008. Vision impairment was defined as a corrected visual acuity of worse than 0.5 (logMAR = 0.3) in the better eye, and hearing impairment was defined as a failure to hear a 30 dB hearing level signal at 1 kHz in the better ear. Information on outcomes was obtained from the town hall and through face-to-face home visit interviews. We calculated the risk ratios (RRs) of AHOs for vision and hearing impairments according to gender. Results. During a mean follow-up period of 3 years, 34 men (10.1%) and 52 women (11.3%) had AHOs. In both genders, vision impairment was related to an elevated risk of AHOs (multi-adjusted RR for men and women together = 1.60, 95% CI = 1.05-2.44), with no statistically significant interaction between the genders. In contrast, a significant association between hearing impairment and AHOs (multi-adjusted RR = 3.10, 95% CI = 1.43-6.72) was found only in the men. Conclusion. In this older Japanese population, sensory impairments were clearly associated with AHOs, and the association appeared to vary according to gender. Gender-specific associations between sensory impairments and AHOs warrant further investigation. © 2009 Michikawa et al; licensee BioMed Central Ltd.

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Effects of the CYP2D6*10 alleles and co-medication with CYP2D6-dependent drugs on risperidone metabolism in patientswith schizophrenia

Yagihashi Tatsuhiko, Mizuno Masafumi, Chino Bun, Sato Yuji, Sakuma Kei, Takebayashi Toru, Takao Takahashi, Kosaki Kenjiro

Human Psychopharmacology 24 （ 4 ） 301 - 308 2009年

研究論文（学術雑誌）, 共著, ISSN 0885-6222

Objective: Risperidone is converted to 9-hydroxyrisperidone by CYP2D6. Two parameters were used to examine the influences of CYP2D6 polymorphism and of co-medication on risperidone metabolism: the risperidone:9-hydroxyrisperidone concentration ratio (R:9-OHR ratio) and the sum of the risperidone and 9-hydroxyrisperidone concentrations divided by the dose (C:D ratio). We evaluated the effect of the CYP2D6*10 allele, which is a prevalent mutant allele among East Asians. Methods: Genotyping using the P450 microarray system was performed for 89 Japanese patients with schizophrenia receiving risperidone. The patients with CYP2D6*1/*1, *1 /*2, or *2/*2 were classified as Group 1, those with one CYP2D6a10 allele (CYP2D6*1/2,10 or *2/*10) were classified as Group 2, and those with two CYP2D6,10 alleles were classified as Group 3. The R:9-OHR and C:D ratios were analyzed using two-way ANOVAs with the CYP2D6 genotype and co-medication with CYP2D6-dependent drugs as independent variables. Results: Both the "genotype" and the "co-medication" factors had significant impacts on the R:9-OHR ratio (p=0.011, p<0.001). The "genotype" factor also had a significant impact on the C:D ratio (p=0.032). However, the "co-medication" factor did not have a significant impact on the C:D ratio (p=0.129). Conclusions: The CYP2D6*10 polymorphism and the presence of co-medication exerted significant influences on the pharmacokinetics of risperidone. Copyright © 2009 John Wiley & Sons, Ltd.

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The taste of salt measured by a simple test and blood pressure in Japanese women and men

Michikawa Takehiro, Nishiwaki Yuji, Okamura Tomonor, Asakura Keiko, Nakano Makiko, Takebayashi Toru

Hypertension Research 32 （ 5 ） 399 - 403 2009年

研究論文（学術雑誌）, 共著, ISSN 0916-9636

Salt intake is an important risk factor for hypertension. Because it has been reported that increased salt intake dulls the taste of salt, measuring the sense of taste might be a good way of identifying individuals who consume excessive salt. Using a recently developed simple salt taste test, we investigated the relationship between the taste of salt and blood pressure. The subjects in this cross-sectional study were 823 Japanese adults (479 women and 344 men) 40 years old or older. Following a taste test with salt-impregnated taste strips, the subjects were divided into two groups: normal (recognition threshold of salt at <1.0% concentration) and taste impaired (≥1.0%). We determined hypertension from the measured blood pressure. In women, the multi-adjusted odds ratio (95% CI) of hypertension in the impaired group was 2.47 (1.53-3.99) compared with the normal group, whereas no significant difference was observed between the two male groups. When we excluded subjects with moderate and severe hypertension, similar findings were observed. A sub-analysis of couples living alone showed a higher prevalence of hypertension among men whose wives were in the impairment group (58.8%) than in the normal group (36.7%, P=0.10). In conclusion, the taste of salt is associated with blood pressure in Japanese women, but not in men. Because most family meals in Japan are prepared by women, educating women about salt reduction may contribute to the prevention of hypertension, not only among women but also among their husbands and family members.

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Prevalence of ulcerative colitis and Crohn's disease in Japan

Asakura Keiko, Nishiwaki Yuji, Inoue Nagamu, Hibi Toshifumi, Watanabe Mamoru, Takebayashi Toru

Journal of Gastroenterology 44 （ 7 ） 659 - 665 2009年

研究論文（学術雑誌）, 共著, ISSN 0944-1174

Purpose: The prevalence of inflammatory bowel diseases is much lower in Asian countries, including Japan, than in Western countries, but it is rapidly increasing. However, no recent reports describe the current prevalence of these diseases in Japan, so we performed a descriptive epidemiological study to remedy this situation and to elucidate various characteristics of inflammatory bowel diseases in this country. Methods: Japan has a nationwide registration system of patients with intractable diseases, including ulcerative colitis and Crohn's disease. To calculate the age-standardized prevalence, we used this registration system to collect patient data, and we obtained detailed population data from the Japanese government's population estimates made in 2003 and 2004 and from the 2005 population census. In addition, information about the characteristics of ulcerative colitis and Crohn's disease patients was collected through the registration system. Results: The age-standardized prevalence of ulcerative colitis in Japan in 2005 was 63.6 per 100,000 persons, and that of Crohn's disease was 21.2. Patient numbers have been steadily increasing with time. The age distribution was found to differ between the two diseases, with Crohn's disease affecting mainly younger people. In both diseases, more than 50% of the patients were male, and over 80% of the patients were classified as mild to moderate in terms of severity. Conclusions: The prevalence of inflammatory bowel diseases in Japan is still much lower than in Western countries. Surveillance should be continued, and research to clarify their etiologies in association with the increasing number of patients in Japan is needed. © Springer 2009.

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Japan Ministry of Health Study on Prevalence of Dry Eye Disease Among Japanese High School Students

武林亨

AMERICAN JOURNAL OF OPHTHALMOLOGY 146 （ 6 ） 925 - 929 2008年12月

研究論文（学術雑誌）, ISSN 0002-9394

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Adipose endocrine function, insulin-like growth factor-1 axis, and exceptional survival beyond 100 years of age

Arai Yasumichi, Takayama Michiyo, Gondo Yasuyuki, Inagaki Hiroki, Yamamura Ken, Nakazawa Susumu, Kojima Toshio, Ebihara Yoshinori, Shimizu Kenichirou, Masui Yukie, Kitagawa Koji, Takebayashi Toru, Hirose Nobuyoshi

Journals of Gerontology - Series A Biological Sciences and Medical Sciences 63 （ 11 ） 1209 - 1218 2008年11月

研究論文（学術雑誌）, 共著, ISSN 1079-5006

Background. Observational studies have demonstrated similarities between the underpinning of frailty and biological features of centenarians, suggesting that adaptability to age-related multiple physiological decline may be a core component of successful aging. The aim of this study is to determine whether hormonal pathways potentially involved in energy homeostasis contribute to survival beyond 100 years of age. Methods. We assessed a total of 252 centenarians (mean [standard deviation (SD)] age, 101.5 (1.8) years, range 100-108 years) using a complete set of biomarkers of adipose endocrine function and the insulin-like growth factor-1 (IGF-1) axis. Conventional risk factors at baseline were also assessed. The participants were followed up for all-cause mortality every 12 months by telephone contact. Results. During 2253 days of follow-up, 208 centenarians (82.5%) died. The lowest tertile of leptin and the highest tertile of tumor necrosis factor-α were associated with higher mortality risk among centenarians after adjusting for age (per 6-month increase), sex, education, smoking, activities of daily living (ADL), cognitive function, and comorbidities (hazard ratio [HR] 1.6; 95% confidence interval [CI], 1.14-2.35; and HR 1.45; 95% CI, 1.00-2.08, respectively). The lowest tertiles of both IGF-1 and IGF binding protein 3 (IGFBP3) were also associated with increased mortality. The adipose risk score, indicating cumulative effects of adipokine dysregulation, was strongly associated with increased mortality risk; ADL; cognitive function; and levels of albumin, cholinesterase, high-density lipoprotein-cholesterol, C-reactive protein, interleukin 6, and IGF-1 at baseline. Conclusions. The results suggested that preservation of adipose endocrine function and the IGF-1 axis may be potentially important for maintaining health and function and promoting survival at an extremely old age. Copyright 2008 by The Gerontological Society of America.

Prevalence of Dry Eye Disease among Japanese Visual Display Terminal Users

Uchino Miki, Schaumberg Debra A., Dogru Murat, Uchino Yuichi, Fukagawa Kazumi, Shimmura Shigeto, Satoh Toshihiko, Takebayashi Toru, Tsubota Kazuo

Ophthalmology 115 （ 11 ） 1982 - 1988 2008年11月

研究論文（学術雑誌）, 共著, ISSN 0161-6420

Objective: To determine the prevalence of dry eye disease (DED) and risk factors among young and middle-aged Japanese office workers using visual display terminals (VDTs). Design: Cross-sectional prevalence survey. Participants: Four thousand three hundred ninety-three Japanese young and middle-aged office workers using VDTs. Intervention: Office workers completed questionnaires sent by e-mail designed to detect dry eye diagnosis and risk factors. Main Outcome Measures: Clinically diagnosed DED was defined as the presence of a previous clinical diagnosis of DED by dry eye specialists or severe symptoms of DED (both dryness and irritation constantly or often). Current symptoms of DED and possible risk factors such as age, duration of VDT use, type of VDT work, environmental factors, presence of systemic diseases, systemic medicine use, smoking history, and contact lens (CL) use were the main outcome measures. We used logistic regression to examine associations between DED and other demographic factors. Results: Of the 4393 office workers, 3549 (80.1%) completed the questionnaire. Clinically diagnosed DED was present in 266 (10.1%) of 2640 male subjects and in 195 (21.5%) of 909 female subjects. Severe symptoms of DED were observed in 711 male and in 436 female participants. More than 4 hours of VDT use was associated with an increased risk of DED (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.40-2.02). In addition, CL use (OR, 3.91; 95% CI, 3.37-4.53) increased the risk of severe dry eye symptoms. Conclusions: Dry eye disease leading to a clinical diagnosis or severe symptoms is prevalent among young and middle-aged Japanese office workers. The condition is more prevalent among females, CL wearers, and prolonged VDT users. Relevant measures directed against the modifiable risks could provide a positive impact on public health and quality of life of office workers. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. © 2008 American Academy of Ophthalmology.

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Gender difference in the relationships between vision and hearing impairments and negative well-being

Harada Sei, Nishiwaki Yuji, Michikawa Takehiro, Kikuchi Yuriko, Iwasawa Satoko, Nakano Makiko, Ishigami Ai, Saito Hideyuki, Takebayashi Toru

Preventive Medicine 47 （ 4 ） 433 - 437 2008年10月

研究論文（学術雑誌）, 共著, ISSN 0091-7435

Objectives: To evaluate the association of hearing impairment, vision impairment and their combination (dual sensory impairment) with negative well-being such as depression, subjective poor health and the reduced functional ability in community-dwelling older adults, and to determine whether any association varies by gender. Methods: Between 2005 and 2006, we objectively examined vision and hearing impairment (using best-corrected visual acuity and pure-tone audiometric test) in 843 people aged 65 years and older (351 males, 492 females) in a rural Japanese town. Through a home visit interview survey using a structured questionnaire, we also collected information on depression (the five-item Geriatric Depression Scale), subjective poor health, and reduced functional activity (the Tokyo Metropolitan Institute of Gerontology's Index of Competence). Results: We observed gender differences in the association between sensory impairment and depression. Multiple logistic regression analysis revealed that hearing impairment in males (adjusted odds ratio: 2.22, 95% confidence interval; 1.07-4.61) and vision impairment in females (1.91, 1.14-3.21) were related to depression. Vision impairment and dual sensory impairment were also associated with subjective poor health and reduced functional activity in both sexes. Conclusions: Sensory impairment is significantly associated with negative well-being in older persons, and its association with depression may differ between males and females. © 2008 Elsevier Inc. All rights reserved.

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Volcanic sulfur dioxide and acute respiratory symptoms on Miyakejima island

Ishigami A., Kikuchi Y., Iwasawa S., Nishiwaki Y., Takebayashi T., Tanaka S., Omae K.

Occupational and Environmental Medicine 65 （ 10 ） 701 - 707 2008年10月

研究論文（学術雑誌）, 共著, ISSN 1351-0711

Objectives: Following a volcanic eruption in 2000, high concentrations of ambient sulfur dioxide (SO₂) are still observed on Miyakejima, Japan despite the reversal 2 years ago of the ban on residents living on the island. This study examines the association between current levels of volcanic SO ₂ and the incidence of acute subjective symptoms in volunteers on Miyakejima. Methods: The authors conducted a follow-up study on 611 healthy volunteers, on a person-hour basis (28 413 person-hours), who visited the island to provide support to residents from February to July 2005. Adverse health symptoms were measured by self-administered diary and exposure was approximated using monitoring data across 14 sites. Associations between incidence rates and increasing SO₂ levels (reference (the lowest), very low, low, middle and high) were examined using Poisson regression. Results: Hourly incidence of cough, scratchy throat, sore throat and breathlessness showed clear exposureresponse relationships with SO₂ concentrations. There were statistically significant risks of those symptoms at relatively low SO ₂ levels. Thus, rate ratios in the 0.6-2.0 ppm exposure band (vs <0.01 ppm) were: for cough, 3.4 (95% Cl 1.8 to 6.6) in men and 9.8 (3.9 to 24.9) in women; for sore throat, 3.2 (1.7 to 6.2) in men and 5.8 (2.0 to 16.5) in women; and for breathlessness, 10.5 (4.2 to 26.6) in men and 18.5 (4.6 to 74.3) in women. Little evidence of SO₂ effects on sputum and nasal discharge/congestion was observed in this study. Eye and skin irritations showed inconsistent results between hourly maximal and hourly mean SO₂ concentrations. Conclusion: The authors observed strong evidence of an exposure-response relationship between volcanic SO₂ and subjective acute respiratory symptoms among a healthy population on Miyakejima. The results are consistent with reports that females and non-smokers are more sensitive to irritant gas than males and smokers, respectively.

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Bronchoscopic microsampling to analyze the epithelial lining fluid of patients with pulmonary Mycobacterium avium complex disease

Nishimura Tomoyasu, Hasegawa Naoki, Watanabe Masazumi, Takebayashi Toru, Tasaka Sadatomo, Ishizaka Akitoshi

Respiration 76 （ 3 ） 338 - 343 2008年09月

研究論文（学術雑誌）, 共著, ISSN 0025-7931

Background: A new bronchoscopic microsampling (BMS) probe has recently been developed, which allows the minimally invasivecollection of epithelial lining fluid (ELF) simultaneously from multiple sites. While the number of immunocompetent patients with pulmonary Mycobacterium avium complex(MAC) disease is growing, the precise pathogenesis of the disease remains to be clarified. Objectives: This study aimed to measure biochemical markers in the ELF of patients with pulmonary MAC disease using BMS. Methods: We studied 8 healthy volunteers (controls) and 8 patients with pulmonary MAC disease. In the patients, ELF was collected from visibly abnormal (involved) and normal (uninvolved) sites using high-resolution computed tomography (HRCT). Results: The concentration of IFN-γ (means ± SEM) was significantly higher in patient ELF sampled from involved (26.62 ± 9.66 pg/ml) than from uninvolved sites (5.33 ± 1.44 pg/ml; p < 0.05) or from normal controls (<1.56 pg/ml; p < 0.05). In most patients, there was no difference in IFN-γ concentrations between the involved and uninvolved sites. The concentration of KL-6 in ELF was significantly higher in the involved (793 ± 108 U/ml) than in the uninvolved sites (192 ± 43 U/ml;p < 0.05) or in normal controls (186 ± 38 U/ml;p < 0.05). Conclusions: The specific inflammatory reaction caused by MAC infection might not be limited to sites that were visibly abnormal on HRCT. Although further improvement has to be considered, BMS may help to increase the understanding of the pathogenesis of various respiratory disorders. Copyright © 2008 S. Karger AG.

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[Iodine concentration in current Japanese foods and beverages].

Kikuchi Yuriko, Takebayashi Toru, Sasaki Satoshi

Nihon eiseigaku zasshi. Japanese journal of hygiene 63 （ 4 ） 724 - 734 2008年07月

研究論文（学術雑誌）, 共著

In the present study, we determined iodine concentration in commonly consumed foods in Japan. One hundred thirty-nine foods and beverages were purchased from local markets and convenience stores. These samples were examined for iodine concentration by using gas chromatography after ashing or extraction. The iodine concentrations in various food groups were as follows, The concentrations in cereals, sugar, sweeteners, vegetables, fruit, milk, and meat were too low to be detected (<0.05 mg/100 g). The iodine concentrations of algae and dashi (Japanese broth or stock) from algae were <0.05-225 mg/100 g; Japanese seasoning, <0.05-10.5 mg/100 g; and iodine-rich eggs, 1.09-2.00 mg/100 g. Food and beverages with high iodine concentrations need to be taken into account in the nutritional survey for health hazards and benefits in the evaluation of daily nutritional intake.

A survey on urinary incontinence among middle aged and older people

Michikawa Takehiro, Nishiwaki Yuji, Kikuchi Yuriko, Nakano Makiko, Takamizawa Megumu, Koike Mieko, Kikuchi Noriko, Mukoyami Yumi, Nakazawa Akemi, Nishigaki Yoshio, Takebayashi Toru

[Nippon kōshū eisei zasshi] Japanese journal of public health 55 （ 7 ） 449 - 455 2008年07月

研究論文（学術雑誌）, 共著, ISSN 0546-1766

OBJECTIVE: Studies in Western countries have revealed that urinary incontinence, non-intentional loss of urine, is a common condition in aged populations, and even younger individuals may suffer from urinary incontinence. However, in Japan, the evidence for community residents on this topic is limited. The aim of this study was to estimate the prevalence of urinary incontinence among middle aged using a structured questionnaire and older people and to provide useful information including frequency, voided volume, relation to parity as a risk factor and persons to consult for this condition. METHODS: The study subjects consisted of 985 residents, 350 males (mean age 62.5 +/- 11.2 years)and 635 females (64.3 +/- 11.4), who participated in annual health check-ups and answered a self-reported questionnaire on urinary incontinence. The questionnaire included questions on frequency, voided volume, condition-specific QOL score, self-diagnostic item (above four from Scored International Consultation on Incontinence Questionnaire-Short Form Japanese version), person to consult for this condition and parity (only for females). RESULTS: The proportion of those with urinary incontinence was 11.4% in males and 34.5% in females, and the proportion increased with age (P for trend <0.01). In females, the proportion was high, even in their forties (30.4%). In this study, parity was associated with urinary incontinence: compared to females with no childbirth experience, those giving birth to 4 or more children showed an odds ratio of 4.26 (95% CI: 1.13-16.10). In females, an increase in frequency of urinary incontinence negatively affected the QOL. When asked who they would consult, the majority of males answered either a medical institution (54.2%) or family (34.0%). In females, 39.6% reported a medical institution, 22.6% reported family, 16.5% reported no one, 10.6% reported health nurses other than in medical institutions and 9.5% reported friends. CONCLUSIONS: The study results showed that urinary incontinence is a common condition in this population. Particularly, a large proportion of females suffer from this condition, even in their forties. The study also revealed that urinary incontinence might negatively affect the QOL and that there are some individuals who do not consult (or intend to consult) anyone about their problem. This information might be useful for planning health policy on the topic in the future.

Marital status and cardiovascular risk factors among middle-aged Japanese male workers

Kamon Yuko, Okamura Tomonori, Tanaka Taichiro, Hozawa Atsushi, Yamagata Zentaro, Takebayashi Toru, Kusaka Yukinori, Urano Sumio, Nakagawa Hideaki, Kadowaki Takashi, Miyoshi Yuji, Yamato Hiroshi, Okayama Akira, Ueshima Hirotsugu

Journal of Occupational Health 50 （ 4 ） 348 - 356 2008年07月

研究論文（学術雑誌）, 共著, ISSN 1341-9145

Marital status is related to cardiovascular disease (CVD) risk factors in Western countries. However, few studies have addressed the relationship between marital status and CVD risk factors in other populations. We investigated lifestyle and CVD risk factors relative to marital status among middle-aged Japanese men. We analyzed baseline data of 40-59-yr-old male workers who participated in the high-risk and population strategy for occupational health promotion (HIPOP-OHP) study. We compared lifestyle and CVD risk factors between men who were married (Group M; n=1,419, mean age 47.9 ±5.1 yr) and those who had never married (Group N; n=163, mean age 46.7 ±4.3 yr). Men in Group N were more likely to skip breakfast, work more shifts and exercise less. Current smoking rates, as well as average values of diastolic blood pressure (DBP), serum total cholesterol and fasting plasma glucose were also higher in Group N than in Group M. The proportion of participants with three or more CVD risk factors, namely smoking, hypertension, hypercholesterolemia and hyperglycemia was higher in Group N, than in Group M (12.9% vs. 5.0%, p<0.01). The difference between Groups M and N was more evident in the subgroup of living with others, than in the subgroup of living alone. Since men who have never married might be at higher risk for CVD, effort should be made to educate this population about decreasing lifestyle-related risk factors.

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Authors' reply

Takebayashi T., Akiba S., Kikuchi Y., Taki M., Wake K., Watanabe S., Yamaguchi Naohito

Occupational and Environmental Medicine 65 （ 6 ） 428 2008年06月

研究論文（学術雑誌）, 共著, ISSN 1351-0711

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Accuracy of an interferon-γ release assay to detect active pulmonary and extra-pulmonary tuberculosis

Nishimura T., Hasegawa Naoki, Mori M., Takebayashi T., Harada N., Higuchi K., Tasaka S., Ishizaka A.

International Journal of Tuberculosis and Lung Disease 12 （ 3 ） 269 - 274 2008年03月

研究論文（学術雑誌）, 共著, ISSN 1027-3719

OBJECTIVE: To examine the performance of an interferon-gamma (IFN-γ) release assay (QuantiFERON-TB 2G assay [QFT-G]) to detect Mycobacterium tuberculosis infection in a Japanese general hospital, for the diagnosis of active pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB). DESIGN: We prospectively examined the performance of QFT-G in 194 patients suspected of active TB. Diagnosis was confirmed by 1) positive M. tuberculosis cultures, or 2) clinical manifestations or laboratory or pathological findings consistent with active TB and response to specific therapy. RESULTS: Three patients with indeterminate QFT-G results were excluded. Among the remaining 191 patients, 77 had active TB. When the cut-off concentration of IFN-γ was set at 0.35 IU/ml, as recommended by the manufacturer, the assay was positive in 69 patients and negative in 122. The sensitivity of the assay was 76.6% in all patients, 74.5% in the 47 patients with PTB and 80.0% in the 30 patients with EPTB. The overall specificity of the assay was 91.2%. CONCLUSION: Although the specificity of the QFT-G to detect active TB was high and its sensitivity low, it was as accurate for the detection of active EPTB as for PTB when the 0.35 IU/ml INF-γ cut-off concentration was used. © 2008 The Union.

Mobile phone use, exposure to radiofrequency electromagnetic field, and brain tumour

Takebayashi T., Varsier N., Kikuchi Y., Wake K., Taki M., Watanabe S., Akiba S., Yamaguchi N.

British Journal of Cancer 98 （ 3 ） 652 - 659 2008年02月

研究論文（学術雑誌）, 共著, ISSN 0007-0920

In a case-control study in Japan of brain tumours in relation to mobile phone use, we used a novel approach for estimating the specific absorption rate (SAR) inside the tumour, taking account of spatial relationships between tumour localisation and intracranial radiofrequency distribution. Personal interviews were carried out with 88 patients with glioma, 132 with meningioma, and 102 with pituitary adenoma (322 cases in total), and with 683 individually matched controls. All maximal SAR values were below 0.1 W kg^-1, far lower than the level at which thermal effects may occur, the adjusted odds ratios (ORs) for regular mobile phone users being 1.22 (95% confidence interval (CI): 0.63-2.37) for glioma and 0.70 (0.42-1.16) for meningioma. When the maximal SAR value inside the tumour tissue was accounted for in the exposure indices, the overall OR was again not increased and there was no significant trend towards an increasing OR in relation to SAR-derived exposure indices. A non-significant increase in OR among glioma patients in the heavily exposed group may reflect recall bias. © 2008 Cancer Research UK.

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Job strain and arteriosclerosis in three different types of arteries among male Japanese factory workers

Michikawa Takehiro, Nishiwaki Yuji, Nomiyama Tetsuo, Uemura Takamoto, O'Uchi Toshihiro, Sakurai Haruhiko, Omae Kazuyuki, Takebayashi Toru

Scandinavian Journal of Work, Environment and Health 34 （ 1 ） 48 - 54 2008年02月

研究論文（学術雑誌）, 共著, ISSN 0355-3140

Objectives: This study evaluated the association between job strain and subclinical indicators of arteriosclerosis simultaneously in the cerebral artery, the aorta, and the carotid artery. Methods: The participants in this cross-sectional study consisted of 352 male factory workers between the ages of 24.9 to 55.8 (mean 41.7) years who had not been exposed to any hazardous chemicals in Japan. Job strain was measured using a Japanese version of the Job Content Questionnaire developed by Karasek. The following subclinical indicators of arteriosclerosis were examined by noninvasive procedures: hyperintense spots in T2-weighted images in brain magnetic resonance imaging (MRI), pulse wave velocity of the aorta, and the stiffness parameter of the carotid artery using ultrasound and systolic and diastolic blood pressure. Results: After control for potential confounders, high job strain was associated with an increased prevalence of hyperintense spots (adjusted odds ratio 2.53, 95% confidence interval 1.14-5.63), and elevated pulse-wave velocity (adjusted increase in percent 3.5, 95% confidence interval 0.0-6.9). The stiffness parameter tended to be elevated in the high job-strain group although this trend was not statistically significant. Job strain showed no relation to blood pressure. Conclusions: In this study, job strain was associated with subclinical indicators of arteriosclerosis in different arteries although the association was not statistically significant for the carotid artery. New information is offered by brain MRI for arteriosclerosis in the cerebral artery. An increase in hyperintense spots may explain the link between job strain and cerebrovascular disease.

Exposure to hardly soluble indium compounds in ITO production and recycling plants is a new risk for interstitial lung damage

Hamaguchi T., Omae K., Takebayashi T., Kikuchi Y., Yoshioka N., Nishiwaki Y., Tanaka A., Hirata M., Taguchi O., Chonan T.

Occupational and Environmental Medicine 65 （ 1 ） 51 - 55 2008年01月

研究論文（学術雑誌）, 共著, ISSN 1351-0711

Objectives: To identify the effects of indium on the lung and to assess exposure-effect and exposure-response relations between indium exposure and effects on the lungs. Methods: Ninety three male indium exposed and 93 male non-exposed workers from four ITO manufacturing or ITO recycling plants were analysed in a cross-sectional study. Indium in serum (In-S) was determined as a biological exposure index. Geometric means (GSD) of In-S were 8.25 ng/ml (4.55) in the exposed workers and 0.25 (2.64) in the non-exposed workers. The maximum concentration of In-S was 116.9 ng/ml. A questionnaire for respiratory symptoms and job histories, spirometry, high-resolution computerised tomography (HRCT) of the chest, serum KL-6, serum SP-A, serum SP-D and serum CRP were measured as the effect indices. Results: Spirometry, subjective symptoms and the prevalence of interstitial or emphysematous changes on lung HRCT showed no differences between exposed and non-exposed workers. Geometric means (GSD) of KL-6, SP-D and SP-A in the exposed workers were 495.4 U/ml (2.26), 85.2 ng/ml (2.02) and 39.6 ng/ml (1.57), and were significantly higher than those in the non-exposed workers. The prevalence (%) of the exposed and non-exposed workers exceeding the reference values were also significantly higher in KL-6 (41.9 vs 2.2), SP-D (39.8 vs 7.5), and SP-A (43.0 vs 24.7). Very sharp exposure-effect and exposure-response relations were discovered between In-S and KL-6 and between In-S and SP-D when the exposed workers were classified into seven groups by In-S. Conclusions: The study outcomes with regard to the basis of serum immunochemistry biomarkers and HRCT indicate that exposure to hardly soluble indium compound dust may represent a risk for interstitial lung damage.

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SAR characterization inside intracranial tumors for case-control epidemiological studies on cellular phones and RF exposure

Varsier Nadège, Wake Kanako, Taki Masao, Watanabe Soichi, Takebayashi Toru, Yamaguchi Naohito, Kikuchi Yuriko

annals of telecommunications - annales des télécommunications 1 - 14 2008年

研究論文（学術雑誌）, 共著, ISSN 0003-4347

Epidemiological studies investigating whether mobile phone use is related to cancer risk have been conducted in many countries. The purpose of the work reported here was to introduce the dose metric in the exposure assessment, taking into account the spatial distribution of exposure. Distributions of specific absorption rate (SAR) inside 275 cases of brain tumors (participants in the Japanese epidemiological study) were estimated. Phones had been classified into four categories based on SAR distributions and technical specifications. Results were found to be highly dependent on phone categories. Contralateral tumors were generally categorized as non-exposed tumors (max SAR <2.5% of max SAR in the brain) and, for any phone category, the maximum SAR in 75% of the ipsilateral tumors was less than 15% of the maximum SAR in the brain. Three new exposure indices combining the duration and strength of exposure were created to be used in the Japanese epidemiological study on mobile phone use and the risk of gliomas and meningiomas. © 2008 GET and Springer Verlag France.

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Standing body balance and fall related factors in community-dwelling elderly persons

Araya Kazufumi, Nishiwaki Yuji, Teragaki Yasuhiro, Kikuti Yuriko, Okamoto Michiko, Takebayashi Toru

Rigakuryoho Kagaku 23 （ 5 ） 597 - 600 2008年

研究論文（学術雑誌）, 共著, ISSN 1341-1667

[Purpose] The purpose of this research was to measure the functional reach (FR) value, as an index of standing balance ability, and to clarify its distribution among community dwelling elderly persons as well as its relationship with fall related factors, such as number of falls in the previous 1 year, history of fracture, and fear of falling. [Subjects] The subjects were 489 persons (226 males, 263 females) over the age of 65 living in K town, Gunma Prefecture, who gave their written consent at the time of their basic health check-up. [Methods] Using a reach measuring apparatus, we performed the FR test, and information regarding fall related factors was gathered by questionnaire. [Results] FR declined in both females and males with advancing age, and at 70 years of age, it had declined significantly in females, as compared to males. Regarding the relationship between FR and the number of falls, a significant decrease in FR was seen among females with 3 or more falls in the past 1 year in a comparison with those with no falls. However, no significant relationship was found between fracture history and fear of falling. [Conclusion] The correlation found between FR values and past number of falls suggests the possibility that FR can be used effectively in local public health programs aiming at fall prevention.

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The short treatment with the angiotensin receptor blocker candesartan surveyed by telemedicine (STAR CAST) study

Sasamura Hiroyuki, Nakaya Hideaki, Julius Stevo, Takebayashi Toru, Sato Yuji, Uno Hajime, Takeuchi Masahiro, Ishiguro Kimiko, Murakami Marohito, Ryuzaki Munekazu, Itoh Hiroshi

Hypertension Research 31 （ 10 ） 1843 - 1849 2008年

研究論文（学術雑誌）, 共著, ISSN 0916-9636

Previous studies have shown that transient treatment of animal models of hypertension with an angiotensin receptor blocker (ARB) causes a sustained decrease in blood pressure values that persists even after the drug treatment is discontinued (J Am Soc Nephrol 12: 659-666, 2001; Nephron 91: 710-718, 2002; Hypertens Res 30: 63-75, 2007). These results have been shown to be clinically relevant by the recent TROPHY study (N Engl J Med 354: 1685-1697, 2006). We have recently found that transient treatment with an ARB may also cause regression of established hypertension in hypertensive rats (J Am Soc Nephrol 18: 157A, 2007). The Short Treatment with the Angiotensin Receptor Blocker Candesartan Surveyed by Telemedicine (STAR CAST) study is a prospective, randomized, open, blinded end-point study in patients aged 30-59 with a positive family history of hypertension that will be conducted in several centers in Japan. The aim of the study is to evaluate the antihypertensive drug withdrawal success rate, the median duration of drug withdrawal, and the changes in home and office blood pressure values in patients with mild hypertension after tapering and withdrawal of antihypertensive treatment following treatment for 1 year with the ARB candesartan or the calcium channel blocker (CCB) nifedipine slow-release. A unique feature of this study is the use of a home blood pressure monitoring telemedicine system (i-TECHO) to allow frequent evaluation of the changes in blood pressure in the trial patients. This study will be the first clinical study to examine if regression from stage 1 (mild) hypertension to prehypertension (high-normal blood pressure) is possible using an ARB or CCB.

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Lactoferrin in Sjögren's Syndrome

Dogru Murat, Matsumoto Yukihiro, Yamamoto Yusuke, Goto Eiki, Saiki Megumi, Shimazaki Jun, Takebayashi Toru, Tsubota Kazuo

Ophthalmology 114 （ 12 ） 2007年12月

研究論文（学術雑誌）, 共著, ISSN 0161-6420

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Evaluation of the control banding method - Comparison with measurement-based comprehensive risk assessment

Hashimoto Haruo, Goto Toshiaki, Nakachi Nobutoyo, Suzuki Hidetaka, Takebayashi Toru, Kajiki Shigeyuki, Mori Koji

Journal of Occupational Health 49 （ 6 ） 482 - 492 2007年11月

研究論文（学術雑誌）, 共著, ISSN 1341-9145

The control banding method, or "control banding", is a simplified risk assessment system for chemical handling tasks. This system is supposed to provide assessment results of reasonable quality without expert involvement. The objective of this study was to evaluate the appropriateness of control banding judgment on the basis of workplace safety. A common approach for assessing workplace risk, which is called "comprehensive risk assessment" in this study, is to measure workers' exposure and compare it with relevant occupational exposure limits. Risk assessment was performed with control banding (COSHH Essentials, UK) at 12 workplaces of a petroleum company in Japan, where health risks had already been assessed separately through comprehensive risk assessment by experts and control technologies implemented accordingly. The obtained control banding judgments were then examined with regard to their adequacy by comparing them with existing control technologies. There was majority of cases (seven) where judgments by control banding were identified as "over-controlled"; there was no judgments identified as "under-controlled". Control banding also requested the seeking of expert advice in the majority of cases (eight). Thus, it was demonstrated that control banding tends to provide safe-sided judgment. A possible interpretation of this is that control banding is inherently designed to secure workplace safety by compensating for its insufficient exposure information with safe-sided judgment criteria and by requiring experts' intervention in high-risk cases. Control banding could be widely and effectively utilized in Japan, especially by employers in small enterprises, provided that the above characteristics are pre-acknowledged and health experts are made available. To this aim, it is essential to develop new local health experts and establish institutional mechanisms for facilitating employers' access to expert advice. It should however be noted that the number of workplaces evaluated in this study was small.

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Awareness and treatment of hypertension and hypercholesterolemia in Japanese workers

Tanaka Taichiro, Okamura Tomonori, Yamagata Zentaro, Takebayashi Toru, Tamura Unai, Kusaka Yukinori, Urano Sumio, Miyoshi Yuji, Okayama Akira, Ueshima Hirotsugu, Sakata Kiyomi, Tsuji Keiko, Yoshita Katsushi, Kikuchi Yuriko, Nakagawa Hideaki, Miura Katsuyuki, Yamato Hiroshi, Chiba Nagako, Yanagita Masahiko, Kodama Kazunori, Kasagi Fumiyoshi, Nishi Nobuo, Saitoh Shigeyuki, Tanaka Hideo, Nakamura Masakazu, Naito Yoshihiko, Nakamura Yasuyuki, Watanabe Makoto, Nakamura Yoshikazu, Babazono Akira, Yamagata Zentaro, Urano Sumio, Kinoshita Fujihisa, Saitoh Isao, Tanihara Shinichi, Tamaki Junko, Tochikubo Osamu, Nakayama Takeo, Fukuhara Shunichi, Fujieda Yoshiharu, Naito Mariko, Mizushima Shunsaku, Miyoshi Yuji, Tada Takayo, Kadowaki Takashi, Yoshida Toshimi, Ide Mami

Hypertension Research 30 （ 10 ） 921 - 928 2007年10月

研究論文（学術雑誌）, 共著, ISSN 0916-9636

The objective of this study was to clarify the awareness and treatment status of hypertension in Japanese workers, comparing with those of hypercholesterolemia. The subjects were 6,186 workers (age 19 to 69 years), who worked at 12 workplaces in Japan and who continuously participated in the High-risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) study at the baseline (1999 or 2000) and the subsequent year (2000 or 2001). No Intervention was performed during the study period. Blood pressure and total cholesterol level were measured at baseline. Awareness and treatment status were examined by a self-administered questionnaire in the following year. Untreated subjects were defined as those were not aware of hypertension (or hypercholesterolemia) or those not taking medication and not undergoing lifestyle modification. The percentages of subjects with hypertension defined as aware were 65.7% in men and 72.7% in women, respectively. The percentages of subjects with hypercholesterolemia defined as aware were 55.7% in men and 58.6% in women, respectively. In subjects 40 years and older, the awareness rate for hypertension was significantly higher than the awareness rate for hypercholesterolemia (75.0% vs. 59.2%, p<0.001). The percentage of untreated subjects with hypertension was significantly lower than the percentage of untreated subjects with hypercholesterolemia (41.0% vs. 57.1%, p<0.001). Although Japanese workers ≥40 years old have a higher awareness of and are more often treated for hypertension than for hypercholesterolernia, there are still many unaware and untreated individuals with either disease in all age groups. It is important to increase the awareness of risk factors in individuals with positive findings for these conditions.

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The INTERPHONE study: design, epidemiological methods, and description of the study population

Cardis Elisabeth, Richardson Lesley, Deltour Isabelle, Armstrong Bruce, Feychting Maria, Johansen Christoffer, Kilkenny Monique, McKinney Patricia, Modan Baruch, Sadetzki Siegal, Schuz Joachim, Swerdlow Anthony, Vrijheid Martine, Auvinen Anssi, Berg Gabriele, Blettner Maria, Bowman Joseph, Brown Julianne, Chetrit Angela, Christensen Helle Collatz, Cook Angus, Hepworth Sarah, Giles Graham, Hours Martine, Iavarone Ivano, Jarus-Hakak Avital, Klaeboe Lars, Krewski Daniel, Lagorio Susanna, Lonn Stefan, Mann Simon, McBride Mary, Muir Kenneth, Nadon Louise, Parent Marie-Elise, Pearce Neil, Salminen Tiina, Schoemaker Minouk, Schlehofer Brigitte, Siemiatycki Jack, Taki Masao, Takebayashi Toru, Tynes Tore, van Tongeren Martie, Vecchia Paolo, Wiart Joe, Woodward Alistair, Yamaguchi Naohito

European Journal of Epidemiology 22 （ 9 ） 647-664 2007年09月

研究論文（学術雑誌）, 共著, 査読有り

炎症性腸疾患の疫学

武林亨，朝倉敬子，西脇祐司

綜合臨床 56 （ 8 ） 2425-2428 2007年08月

研究論文（学術雑誌）, 共著, ISSN 0371-1900

女性の静止立位作業による血圧低下の実態調査

加部勇，鶴岡寛子，徳地谷洋子，遠藤裕一，古沢真実，武林亨

産業衛生学雑誌 49 （ 4 ） 122-126 2007年07月

研究論文（学術雑誌）, 共著, 査読有り

Investigation of postural hypotension due to static prolonged standing in female workers.

Kabe Isamu, Tsuruoka Hiroko, Tokujitani Yoko, Endo Yuichi, Furusawa Mami, Takebayashi Toru

Sangyō eiseigaku zasshi = Journal of occupational health 49 （ 4 ） 122 - 126 2007年07月

研究論文（学術雑誌）, 共著, ISSN 1341-0725

The "Just-in-Time system" improves productivity and efficiency through cost reduction while it makes workers work in a standing posture. The aim of this study was to investigate the prevalence of postural hypotension in females during prolonged standing work, and to discuss preventive methods. Twelve female static standing workers (mean age+/-standard deviation; 32+/-14 yr old), 6 male static standing workers (30+/-4 yr old), 10 female walking workers (27+/-7 yr old) and 9 female desk workers (31+/-5 yr old) in a certain telecommunications equipment manufacturing factory agreed to participate in this study. All participants received an interview with an occupational physician, and performed the standing up test before working and ambulatory blood pressure monitoring (ABPM) while working. Although the blood pressure of the standing up test did not differ among the groups, mean pulse rates on standing up significantly increased in every group. Hypotension rates in the female standing workers' group by ABPM were 9 persons of 12 participants (75%) for systolic blood pressure (SBP), and were 11 persons of 12 participants (92%) for diastolic blood pressure (DBP). There were significantly higher than those in the female desk workers' group, none of 9 participants (0%) for SBP and 2 of 9 participants (22%) for DBP. The hypotension rates both male standing and female walking worker groups did not differ. Because all 8 workers who were found to have postural hypotension by the standing up test had decreased SBP and/or DBP by ABPM, it is suggested that persons at high risk of postural hypotension during standing work could be screened by the standing up test. The mechanism of postural hypotension may be a decrease of venous return due to leg swelling, and neurocardiogenic or vasovagal response. Preventing the congestion of the lower limbs by walking, managing standing time and wearing elastic hose to keep the amount of the venous return could prevent postural hypotension during prolonged standing work.

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職域におけるポピュレーション・アプローチを用いた生活習慣病危険因子の改善（HIPOP-OHP研究）

岡村智教、田中太一郎、由田克士、武林亨、大和浩、三浦克之、中川秀昭、日下幸則、岡山明、山縣然太朗、上島弘嗣

産業医学ジャーナル 30 （ 2 ） 59-64 2007年03月

研究論文（学術雑誌）, 共著

Association of thoracic kyphosis with subjective poor health, functional activity and blood pressure in the community-dwelling elderly

Nishiwaki Yuji, Kikuchi Yuriko, Araya Kazufumi, Okamoto Michiko, Miyaguchi Shingo, Yoshioka Noriyuki, Shimada Naoki, Nakashima Hiroshi, Uemura Takamoto, Omae Kazuyuki, Takebayashi Toru

Environmental Health and Preventive Medicine 12 （ 6 ） 246 - 250 2007年

研究論文（学術雑誌）, 共著, ISSN 1342-078X

Objectives: The prevalence of thoracic kyphosis is considered to increase as the population is ageing in Japan. However, little is known about the clinical and preventive significance of kyphosis. The purpose of the study is to assess the association of kyphosis with subjective poor health and functional activity in the community-dwelling Japanese elderly. The relation of kyphosis with blood pressure, as a subclinical indicator of arteriosclerosis, is also examined. Methods: The subjects consisted of 536 (male 241, female 295) elderly persons aged 65 years old and older. Trained examiners measured thoracic kyphosis using a flexicurve, and kyphosis index was calculated. Information on the subjects' subjective poor health and functional activity were collected through a face-to-face interview, and blood pressure was measured by a conventional method. Results: In females, their kyphosis index increased with age increased, whereas in males, there was no clear age-related change. An increased kyphosis index was associated with subjective poor health only among females. Compared with the lowest kyphosis index tertile, adjusted odds ratios for being in poor health were 5.4 (95% confidence interval: 1.1-27.4) in the middle tertile, and 6.4 (95% confidence interval: 1.3-32.1) in the highest tertile. Kyphosis index did not seem to be associated with functional activity score and blood pressure both in males and females even after adjustment. Conclusions: Kyphosis is associated with subjective poor health in the community-dwelling female elderly in this study population, but not with functional activity and blood pressure both in males and females.

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Mobile phone use and acoustic neuroma risk in Japan

Takebayashi T., Akiba S., Kikuchi Y., Taki M., Wake K., Watanabe S., Yamaguchi N.

Occupational and Environmental Medicine 63 （ 12 ） 802 - 807 2006年12月

研究論文（学術雑誌）, 共著, ISSN 1351-0711

Objectives: The rapid increase of mobile phone use has increased public concern about its possible health effects in Japan, where the mobile phone system is unique in the characteristics of its signal transmission. To examine Hie relation between mobile phone use and acoustic neuroma, a case-control study was initiated. Methods: The study followed the common, core protocol of the international collaborative study, INTERPHONE. A prospective case recruitment was done in Japan for 2000-04. One hundred and one acoustic neuroma cases, who were 30-69 years of age and resided in the Tokyo area, and 339 age, sex, and residency matched controls were interviewed using a common computer assisted personal interview system. Education and marital status adjusted odds ratio was calculated with a conditional logistic regression analysis. Results: Fifty one cases (52.6%) and 192 controls (58.2%) were regular mobile phone users on the reference date, which was set as one year before the diagnosis, and no significant increase of acoustic neuroma risk was observed, with the odds ratio (OR) being 0.73 (95% CI 0.43 to 1.23). No exposure related increase in the risk of acoustic neuroma was observed when the cumulative length of use (<4 years, 4-8 years, >8 years) or cumulative call time (<300 hours, 300-900 hours, >900 hours) was used as an exposure index. The OR was 1.09 (95% CI 0.58 to 2.06) when the reference date was set as five years before the diagnosis. Further, laterality of mobile phone use was not associated with tumours. Conclusions: These results suggest that there is no significant increase in the risk of acoustic neuroma in association with mobile phone use in Japan.

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Deinstitutionalization of long-stay patients with schizophrenia: the 2-year social and clinical outcome of a comprehensive intervention program in Japan

Ryu Yonosuke, Mizuno Masafumi, Sakuma Kei, Munakata Shunichi, Takebayashi Toru, Murakami Masaaki, Falloon Ian RH, Kashima Haruo

Australian and New Zealand Journal of Psychiatry 40 （ 5 ） 462-470 2006年05月

研究論文（学術雑誌）, 共著, 査読有り

三宅島帰島に向けての健康リスクコミュニケーション

菊池有利子，武林亨，大前和幸

日本胸部臨床 65 （ 3 ） 252-260 2006年03月

研究論文（学術雑誌）, 共著, 査読有り

Excess mortality of schizophrenia in the developing country of Bali

Kurihara Toshiyuki, Kato Motoichiro, Kashima Haruo, Takebayashi Toru, Reverger Robert, I Gusti Rai Tirta

Schizophrenia Research 83 （ 1 ） 103-105 2006年03月

研究論文（学術雑誌）, 共著, 査読有り

The Sasagawa Project: A model for deinstitutionalisation in Japan

Mizuno Masafumi, Sakuma Kei, Ryu Yonosuke, Munakata Shunichi, Takebayashi Toru, Murakami Masaaki, Falloon R.H. Ian, Kashima Haruo

Keio Journal of Medicine 54 （ 2 ） 95-101 2005年06月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0022-9717

【日本人の食事摂取基準(2005年版)】　ヨウ素．

武林亨

臨床栄養 106 （ 1 ） 45-47 2005年01月

研究論文（学術雑誌）, 単著

Applicability of the stages of change model for analyzing fruit and vegetable intake in relation to urinary potassium excretion: baseline results from the High-risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) Study.

Tamaki Junko, Yoshita Katsushi, Kikuchi Yuriko, Takebayashi Toru, Chiba Nagako, Okamura Tomonori, Tanaka Taichiro, Kasagi Fumiyoshi, Minai Junko, Ueshima Hirotsugu, the HIPOP-OHP research group.

Hypertension Research 27 （ 11 ） 843-850 2004年11月

研究論文（学術雑誌）, 共著, 査読有り

【2005年改定日本人の食事摂取基準】　上限量（UL）

武林亨

臨床栄養 105 （ 6 ） 712-714 2004年11月

研究論文（学術雑誌）, 単著

Interview study on autonomous chemical management system and the contribution of occupational health specialists in companies

Mori Koji, Takebayashi Toru

Sangyo eiseigaku zasshi = Journal of occupational health 46 （ 5 ） 181 - 187 2004年09月

研究論文（学術雑誌）, 共著, ISSN 1341-0725

Under the circumstance that autonomous risk management for chemicals is required in Japan, it is necessary to define fundamental steps for developing chemical management system that are applicable in various types of companies and to understand the effective contribution of chemical or occupational health specialists to the system. For the purposes, we conducted interviews with companies which have an advanced chemical management system in Japan. As the result, each company had a certain policy about detailedness level of collected hazard and exposure information, and also had an efficient risk management system to ensure workers' health in depending on the business type and situations. Moreover, it was commonly observed that the specialists played major roles in developing tools for risk assessment and control, and then business lines led execution of the risk management with their supports. Based on the interviews, we showed a hypothesis of basic steps in introducing autonomous chemical risk management system at the workplaces. It is necessary to verify the hypothesis and to develop a simple system that is applicable to middle or small size companies as the next step.

化学物質の自主管理における企業内システムと専門家の関与に関するインタビュー調査

森晃爾，　武林亨

産業衛生学雑誌 46 （ 5 ） 181-187 2004年09月

研究論文（学術雑誌）, 共著, 査読有り

Methodological issues for a large-scale intervention trial of lifestyle modification

Okamura Tomonori, Tanaka Taichiro, Takebayashi Toru, Nakagawa Hideaki, Yamato Hiroshi, Yoshita Katsushi, Kadowaki Takashi, Okayama Akira, Ueshima Hirotsugu

Environmental Health and Preventive Medicine 9 （ 4 ） 137 - 143 2004年07月

研究論文（学術雑誌）, 共著, ISSN 1342-078X

Objective: To clarify the methodological issues for the High-risk and Population Strategy for Occupational Health Promotion Study (HIPOP-OHP study), which is a 4-year non-randomized control trial, an interim assessment of male participants was performed 3 years after the baseline survey. Methods: We had approximately 2,500 and 4,000 participants in the intervention and control groups, respectively. The population measures and prevalence of risk factors at each year, and between the baseline and 4th examinations were compared between the two groups. The personal trends of returning participants who were in the study at the 1st and 4th examinations were also evaluated. Results: During the 3 years, an increase in serum HDL cholesterol (2.7 mg/dl), and a reduction in the prevalence of hypertriglycemia detected with fasting blood samples (3.6%) and current smokers (5.4%) were observed in the intervention group. The mean HDL cholesterol level was significantly higher in the intervention group than in the control group at the 4th examination, reversed from the baseline survey. The serum non-HDL cholesterol level was significantly increased only in the control group. There was also a significant increase in the prevalence of hypertriglycemia and high plasma glucose detected with fasting blood samples in the control group. The return participation rate after 3 years was 72.2% for the intervention group and 74.9% for the control group. The above-mentioned changes for risk factors were mainly due to returning participants at each examination. Conclusion: These interventional methods may be effective in improving overall cardiovascular risk factors in the population. However, the low return participation rate will dilute the effect of the intervention.

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The evaluation of materials to provide health-related information as a population strategy in the worksite: the High-risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) Study

Yoshita Katsushi, Tanaka Taichiro, Kikuchi Yuriko, Takebayashi Toru, Chiba Nagako, Tamaki Junko, Miura Katsuyuki, Kadowaki Takashi, Okamura Tomonori, Ueshima Hirotsugu, the HIPOP-OHP study research group

Environmental Health and Preventive Medicine 9 （ 4 ） 144-151 2004年07月

研究論文（学術雑誌）, 共著, 査読有り

Methodological issues for a large-scale intervention trial of lifestyle modification: Interim assessment of The High-risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) Study

Okamura Tomonori, Tanaka Taichiro, Takebayashi Toru, Nakagawa Hideaki, Yamato Hiroshi, Yoshita Katsushi, Kadowaki Takashi, Okayama Akira, Ueshima Hirotsugu, the HIPOP-OHP research group

Environmental Health and Preventive Medicine 9 （ 4 ） 137-143 2004年07月

研究論文（学術雑誌）, 共著, 査読有り

The High-risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) Study: Study design and cardiovascular risk factors at the baseline survey

Okamura Tomonori, Tanaka Taichiro, Babazono Akira, Yoshita Katsushi, Chiba Nagako, Takebayashi Toru, Nakagawa Hideaki, Yamato Hiroshi, Miura Katsuyuki, Tamaki Junko, Kadowaki Takashi, Okayama Akira, Ueshima Hirotsugu, the HIPOP-OHP research group

Journal of Human Hypertension 18 （ 7 ） 475-485 2004年07月

研究論文（学術雑誌）, 共著, 査読有り

The evaluation of materials to provide health-related information as a population strategy in the worksite

Yoshita Katsushi, Tanaka Taichiro, Kikuchi Yuriko, Takebayashi Toru, Chiba Nagako, Tamaki Junko, Miura Katsuyuki, Kadowaki Takashi, Okamura Tomonori, Ueshima Hirotsugu

Environmental Health and Preventive Medicine 9 （ 4 ） 144 - 151 2004年07月

研究論文（学術雑誌）, 共著, ISSN 1342-078X

Objective: To examine the effectiveness of newly developed materials for providing health-related information to the worksite population, we compared the amount of attention that employees paid to the materials. Methods: Study subjects were 2,361 employees in six companies partcipating in an intervention program between 2002 and 2003. Three kinds of media were used as tools for providing health information: [1] Point Of Purchase advertising menus (POP menus) were placed on all tables in company restaurants, [2] posters were put on walls and [3] leaflets were distributed at health-related events. One year or more after the introduction of these media, we compared the amount of attention paid to each type of medium. Results: Amongst the three types of media, the POP menu drew the most attention, although results were not consistent in all gender and company groups. Every piece of information provided by the POP menus was "always" or "almost always " read by 41% of the men and 51% of the women surveyed. The corresponding rate for posters was 30% in men and 32% in women. For leaflets, only 16% of men and 22% of women read almost all of the leaflets. More attention was paid to the POP menu when the sample was women, older, and ate at the company restaurant at least three times a week. Conclusion: The POP menu may provide health-related information to a broader range of people than posters and leaflets, therefore, it is an effective material for population strategy.

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事業場における自律的な健康リスクの管理　?化学物質のリスクアセスメント?

武林亨

労働の科学 59 （ 6 ） 354-358 2004年06月

研究論文（学術雑誌）, 単著, ISSN 0035-7774

Six year observational cohort study of the effect of carbon disulphide on brain MRI in rayon manufacturing workers

Nishiwaki Y., Takebayashi T., O'Uchi T., Nomiyama T., Uemura T., Sakurai H., Omae K.

Occupational and Environmental Medicine 61 （ 3 ） 225 - 232 2004年03月

研究論文（学術雑誌）, 共著, ISSN 1351-0711

Aims: To clarify whether the current occupational exposure limit (OEL) for carbon disulphide (CS₂) is low enough to prevent the occurrence of adverse effects on the cerebrovascular system. Methods: A total of 432 male workers exposed to CS₂ and 402 male referent workers in 11 Japanese viscose rayon factories were studied at baseline; 750 of these were followed up. Brain MRI was performed at both baseline and follow up surveys. Changes in the number of hyperintense spots in T2 weighted images (HIS), which point to so-called "silent cerebral infarctions", were evaluated over six years. A total of 666 subjects (217 exposed, 125 ex-exposed, and 324 referent subjects) who twice received brain MRI were subjected to analysis. Mean duration of exposure to the end of the study was 19.6 years for the exposed workers. The geometric mean CS₂ (ppm) and TTCA (mg/g creatinine) concentrations for the past six years were 4.9 and 1.6 for all exposed workers, 5.8 and 1.9 for spinning/refining workers, and 2.7 and 0.9 for other exposed workers, respectively. Results: Exposed subjects showed a significantly higher risk for an increase in the number of HIS over six years. Odds ratios adjusted for possible confounders in the exposed and ex-exposed workers were 2.27 (95% CI 1.37 to 3.76) and 1.33 (95% CI 0.70 to 2.54), respectively. No exposure-response relations were observed in a number of analyses among the exposed workers. Conclusions: Exposure to CS₂ under the current Japanese OEL, 10 ppm, might increase the number of HIS in brain MRI. However, results should be interpreted with caution.

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Stages of change for salt intake and urinary salt excretion: Baseline results from the High-risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) Study

Tamaki Junko, Kikuchi Yuriko, Yoshita Katsushi, Takebayashi Toru, Chiba Nagako, Tanaka Taichiro, Okamura Tomonori, Kasagi Fumiyoshi, Minai Junko, Ueshima Hirotsugu, the HIPOP-OHP research group

Hypertension research 27 （ 3 ） 157-166 2004年03月

研究論文（学術雑誌）, 共著, 査読有り

A six year follow up study of the subclinical effects of carbon disulphide exposure on the cardiovascular system

Takebayashi T., Nishiwaki Y., Uemura T., Nakashima H., Nomiyama T., Sakurai H., Omae K.

Occupational and Environmental Medicine 61 （ 2 ） 127 - 134 2004年02月

研究論文（学術雑誌）, 共著, ISSN 1351-0711

Aims: A six year prospective cohort study was conducted to clarify whether the current carbon disulphide (CS₂) exposure level is low enough to prevent subclinical health impairment and/or to ameliorate health effects due to previous high exposure. This paper describes the effects on the cardiovascular systems. Methods: The study subjects were 432 male workers exposed to CS₂ and 402 non-exposed workers in Japan, all of whom were examined in 1992-93. A total of 251 CS₂ exposed, 140 formerly exposed, and 359 non-exposed workers participated in the follow up survey (follow up rate 89.9%) in 1998-99. Mean duration of exposure was 19.3 years at the end the study. Mean CS₂ and 2-thiothiazolidine-4-carboxylic acid (TTCA) concentrations were 5.0 ppm and 1.6 mg/g creatinine. Health items examined were serum biochemical indices including lipids and coagulation-fibrinolysis factors, blood pressure, aortic stiffness, ophthalmography, and electrocardiography at rest and after Master's double 2 step test. Potential confounding factors were adjusted for. Results: Incidence of ischaemic findings, defined as Minnesota codes I, IV_1-3, V _1-3 (at rest and after the load), or receiving treatment for ischaemia, was significantly higher in the exposed workers, especially for the spinning/refining workers (adjusted OR 2.1; 95% CI 1.1 to 4.0) or the highest quartile of six year mean TTCA (adjusted OR 3.9; 95% CI 1.8 to 8.7), although the observed increase in risk was diminished when rigorous ECG criteria were applied. Incidence of retinal microaneurysm was increased with marginal significance. Among cardiovascular risk factors we examined, only blood pressure values were significantly increased in the exposed workers. Conclusions: Increased risk of ischaemic electrocardiogram findings among Japanese viscose rayon workers was observed. Although its clinical significance is to be discussed, the current Japanese occupational exposure limit for CS ₂, 10 ppm, would be high to prevent subclinical cardiovascular effects in this study population.

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Specific alcoholic beverage and blood pressure in a middle-aged japanese population: the High-risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) Study

Okamura Tomonori, Tanaka Taichiro, Yoshita Katsushi, Chiba Nagako, Takebayashi Toru, Kikuchi Yuriko, Tamaki Junko, Tamura Unai, Minai Junko, Kadowaki Takashi, Miura Katsuyuki, Nakagawa Hideaki, Tanihara Shinichi, Okayama Akira, Ueshima Hirotsugu, the HIPOP-OHP research group.

Journal of human hypertension 18 （ 1 ） 39341 2004年01月

研究論文（学術雑誌）, 共著, 査読有り

コニカミノルタグループにおける化学物質自主管理とリスク対策の実例

朝武真由美，　武林亨

働く人の安全と健康 54 （ 10 ） 975-980 2003年10月

研究論文（学術雑誌）, 共著

Biological monitoring of indium by means of graphite furnace atomic absorption spectrophotometry in workers exposed to particles of indium compounds

Miyaki Koichi, Hosoda Kanae, Hirata Miyuki, Tanaka Akiyo, Nishiwaki Yuji, Takebayashi Toru, Inoue Naohide, Omae Kazuyuki

Journal of Occupational Health 45 （ 4 ） 228 - 230 2003年07月

研究論文（学術雑誌）, 共著, ISSN 1341-9145

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Lack of relationship between occupational exposure to carbon disulfide and endocrine dysfunction: a six-year cohort study of the Japanese rayon workers

Takebayashi Toru, Nishiwaki Yuji, Nomiyama Tetsuo, Uemura Takamoto, Yamauchi Tsuneyuki, Tanaka Shigeru, Sakurai Haruhiko, Omae Kazuyuki, the Japanese Rayon Workers' Health Study Group

Journal of occupational health 45 （ 2 ） 111-118 2003年03月

研究論文（学術雑誌）, 共著

Uptake of cadmium in meals from the digestive tract of young non-smoking Japanese female volunteers

Kikuchi Yuriko, Nomiyama Tetsuo, Kumagai Nami, Dekio Fumiko, Uemura Takamoto, Takebayashi Toru, Nishiwaki Yuji, Matsumoto Yukio, Sano Yuri, Hosoda Kanae, Watanabe Shaw, Sakurai Haruhiko, Omae Kazuyuki

Journal of Occupational Health 45 （ 1 ） 43 - 52 2003年01月

研究論文（学術雑誌）, 共著, ISSN 1341-9145

Objectives - To estimate rates of cadmium (Cd) uptake from the digestive tract and changes in Cd in biological specimens after intake of Cd mainly in rice. Methods - Twenty-five young non-smoking Japanese female volunteers (20-23 in age) were recruited and a 20-d experimental study was conducted. With polished rice containing 0.004 ppm and 0.340 ppm of Cd, Meal L and Meal H were prepared. Approximately 12% of total Cd in Meal L and 92% of total Cd in Meal H originated in rice. The volunteers ate Meal L for 11 d to achieve a stable intake-output balance of Cd. Fifteen of the 25 volunteers ate Meal H on the 12^th day (Group D1), and the remaining 10 ate Meal H on the 12^th, 13^th and 14^th day (Group D3). All 25 subjects then resumed the consumption of Meal L to the end of the study (20^th day). All meals, feces and urine were collected during the study, and Cd intake from the daily meals (Cd-I), Cd in feces (Cd-F) and Cd in urine (Cd-U) were determined. For measurement of Cd in blood (Cd-B), venous blood was collected from all volunteers on the day before the study and again on the 12^th and 20^th day; venous blood was also collected from 4-8 volunteers at additional time points. Results - Mean Cd-I was 4.51 μg/d (range: 1.85-6.93) or 48.48 μg/d (range: 27.98-56.27) when they ate Meal L or Meal H. Cd-F and Cd-B exhibited faster responses to the change in Cd-I than did Cd-U. The Cd_uptake rate, defined as (1-Cd-F_excess/Cd-I_excess) (Fig. 1), was 47.2% (range: -9.4-83.3%) in Group D1 and 36.6% (range: -9.2-73.5%) in Group D3, and the Cd_balance rate, defined as (1-Cd-F_output/Cd-I_intake), was 23.9% (range: -4.0-37.7%) in Group D1 and 23.7% (range: -8.2-56.9%) in Group D3. Conclusions - Cd-F and Cd-B are better biological monitoring parameters for assessing change in Cd-I than Cd-U. The Cd_uptake and Cd_balance rates appeared to be higher than those in previous papers when ingested Cd mainly originated in rice.

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食の安全性を科学する（6）リスクコミュニケーション

武林亨

臨床栄養 101 （ 6 ） 632 2002年12月

研究論文（学術雑誌）, 単著

食の安全性を科学する（5）食品添加物の安全性評価

武林亨

臨床栄養 101 （ 4 ） 376 2002年10月

研究論文（学術雑誌）, 単著

食の安全性を科学する（4）食事摂取基準の許容上限摂取量

武林亨

臨床栄養 101 （ 2 ） 144 2002年08月

研究論文（学術雑誌）, 単著

食の安全性を科学する（3）発がん性の評価

武林亨

臨床栄養 100 （ 7 ） 840 2002年06月

研究論文（学術雑誌）, 単著

食の安全性を科学する（2）ダイオキシン類の一日耐容摂取量

武林亨

臨床栄養 100 （ 4 ） 408 2002年04月

研究論文（学術雑誌）, 単著

食の安全性を科学する（1）Dosis sola facit venenum

武林亨

臨床栄養 100 （ 2 ） 144-144 2002年02月

研究論文（学術雑誌）, 単著

The introduction of an occupational health management system for solving issues in occupational health activities in Japan

Mori Koji, Takebayashi Toru

Industrial Health 40 （ 2 ） 167 - 174 2002年

研究論文（学術雑誌）, 共著, ISSN 0019-8366

An important challenge to occupational health services in Japan is the necessary shift from regulation-based occupational health program to health risk-based program. The Occupational Safety and Health Management System (OSHMS) is an effective tool for introducing risk-based activities. To date, the Five Management system has been used to manage occupational health activities. This classification, however, does not show the interactions among the listed activities. Nor is it clear how this system contributes to the PDCA (Plan/Do/Check/Act) cycle for continual improvement. The category in the Five Management system called "Roles of the Occupational Physician" covers most of the occupational health services required in Japan. The items listed in the Five Management system were compared to the guidelines of OSHMS from the International Labour Office and issues that should be solved for occupational health activities with OSHMS were clarified. Seven issues are discussed in this paper; (1) occupational safety and health policy and audit that can drive the PDCA cycle effectively, (2) reclassification of occupational health activities with several different objectives, (3) set up of targets, (4) risk assessment methods that can prioritize health risks compared to safety risks, (5) exposure assessment methods for risk assessment, (6) flexibility of laws and regulations, and (7) development of talented professionals for risk-based occupational health activities.

Urinary excretion of TTCA after intake of brassica vegetables

Kikuchi Yuriko, Uemura Takamoto, Yamauchi Tsuneyuki, Takebayashi Toru, Nishiwaki Yuji, Yamada Kenichi, Sakurai Haruhiko, Omae Kazuyuki

Journal of Occupational Health 44 （ 3 ） 151 - 155 2002年

研究論文（学術雑誌）, 共著, ISSN 1341-9145

Aim: Recent studies have made it clear that brassica vegetables contain 2-thiothiazolidine-4-carboxylic acid (TTCA), which is the most widely used biological monitoring index of exposure to carbon disulfide (CS₂). This study aimed to assess the time-course of TTCA excretion in urine (TTCA-U) after eating brassica vegetables. Methods: After a 1-d break from eating brassica vegetables, ten volunteers (6 males and 4 females) ingested 100 grams of chopped raw cabbage containing 4.3 mg/kg of TTCA, and the TTCA concentration in urine samples was determined over 24 h. TTCA concentrations in brassica vegetables purchased from a local supermarket were also measured. Results: TTCA-U reached peak concentrations 3-9 h after cabbage intake, gradually decreased, and was below the detection limit (<0.1 mg/l) in 8 of 10 volunteers in the last urine samples. The total amount of TTCA excreted in 24 h ranged from 0.19 to 0.42 mg, and half of the total TTCA was excreted within 6.5 h on average (range: 4.5-10.1). The excretion profiles of young and middle-aged volunteers seemed to differ, but not those of young males and young females. TTCA was detected in both raw and boiled cabbage, Japanese radish, turnip, and broccoli, but was not detected in Chinese cabbage or chingentsuai. Conclusion: TTCA-U may be overestimated as an index of CS₂ exposure when brassica vegetables are ingested within approximately 24 h before collection of the urine sample.

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Four-week inhalation toxicity study of 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123) in guinea pigs

Kabe Isamu, Takebayashi Toru, Nishiwaki Yuji, Nakajima Tamie, Ikeda Eiji, Saito Takehito, Tanaka Shigeru, Miyauchi Hiroyuki, Endo Yuichi, Omae Kazuyuki

Journal of Occupational Health 43 （ 6 ） 314 - 320 2001年

研究論文（学術雑誌）, 共著, ISSN 1341-9145

Groups of eight male Hartley guinea pigs were exposed to 30, 100 or 300 ppm 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123) by inhalation for 6 hours a day for 4 wk. All the animals were sacrificed 48 h postexposure. Guinea pigs exposed to 300 ppm HCFC-123 had significantly lower body weight and the weight gain than controls, but there was no significant difference and no tendency in absolute and relative organ weight. ICDH, ALT and AST, which were the most sensitive indicators of halothane-induced liver injury, did not differ significantly between exposed groups and controls. In the 100 ppm group, a few vacuolar fatty changes in the portal area (zone I) were identified. In the 300 ppm group, severe fatty degeneration was observed in the portal and intermediate areas, partly centrilobule, and the incidence increased significantly compared to the controls. On the other hand, there was no histopathological change in the control or 30 ppm groups. No increase in any of the liver peroxisomal enzymes (AOX, PT, catalase) was seen in male guinea pigs exposed to HCFC-123. The activity of hepatic ALDH was significantly decreased in the 300 ppm exposed group, suggesting that HCFC-123 or its metabolite inhibited ALDH activity. In conclusion, inhalation exposure to 100 ppm or more of HCFC-123 for 4 wk produced nonfatal liver change in guinea pigs, namely hepatic fatty changes predominantly in the portal area (zone I) without any increase in AST, ALT or ICDH. The no-observed-adverse-effect level (NOAEL) of HCFC-123 for four wk in guinea pigs may be 30 ppm. Peroxisome proliferation, which may result in hepatocellular tumor induction, was not observed in guinea pigs exposed to HCFC-123.

Cross-sectional study of health effects of methyl methacrylate monomer among dental laboratory technicians

Nishiwaki Yuji, Saitoh Takehito, Takebayashi Toru, Tanaka Shigeru, Etoh Norihito, Eitaki Yoko, Omae Kazuyuki

Journal of Occupational Health 43 （ 6 ） 375 - 378 2001年

研究論文（学術雑誌）, 共著, ISSN 1341-9145

Relationship between the blood coagulation-fibrinolysis system and the subclinical indicators of arteriosclerosis in a healthy male population.

Nishiwaki Y., Takebayashi T., Omae K., Ishizuka C., Nomiyama T., Sakurai H.

Journal of epidemiology / Japan Epidemiological Association 10 （ 1 ） 34 - 41 2000年01月

研究論文（学術雑誌）, 共著, ISSN 0917-5040

A cross-sectional observation was performed to assess the relationship between the coagulation-fibrinolysis system and the subclinical indicators of arteriosclerosis in a healthy male population. Subjects were 445 workers (18.9-49.4, Av. 36.2 yrs) in viscose rayon manufacturing factories in Japan. Coagulation-fibrinolysis parameters determined were D-dimer(DD), thrombin antithrombin III complex (TAT), tissue plasminogen activator (TPA), and plasminogen activator inhibitor 1 (PAI1). The following indicators of arteriosclerosis were examined; systolic and diastolic blood pressure (SBP, DBP), stiffness parameter of the carotid artery using ultrasound (beta), pulse wave velocity of the aorta (PWV), and a number of lacunar infarctions from brain MRI. After age-stratification(-29, 30-39, 40+ yrs), the subjects were classified into quartiles by coagulation-fibrinolysis parameters. The mean values of SBP and DBP and beta and PWV, the prevalence of brain infarctions were compared across these quartiles by means of analysis of variance, chi-square test, respectively. Multivariate analysis was also employed to adjust other risk factors. In conclusion, SBP and DBP and beta, PWV were elevated by increase of PAI1, TAT, respectively, in the 40+ years group even after adjustment for other possible risk factors. DD had no relation to any of the indicators of arteriosclerosis. None of the coagulation-fibrinolysis parameters had any relation to brain infarctions.

Acute and recurrent hepatitis induced by 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123)

Omae K., Takebayashi T., Tanaka S., Sasaki K., Miyauchi H., Kabe I., Taneichi K., Shibaki H.

Journal of Occupational Health 42 （ 5 ） 235 - 238 2000年

研究論文（学術雑誌）, 共著, ISSN 1341-9145

A 49-yr-old female cleaning worker first visited a hospital because of acute hepatitis. On admission, laboratory examination revealed severe hepatic damage (AST 2125 IU/L, ALT 2391 IU/L, LDH 1279 IU/L, t-Bil 8.5 mg/d/), but failed to disclose any evidence of viral infection or morphological lesions. She recovered day by day without any specific treatment for hepatitis and was discharged one month later. On the 11th day after restarting her job, she was readmitted due to similar symptoms and signs. Serum biochemistry data again showed severe liver damage (AST 1354, ALT 1604, LDH 1119 t-Bil 2.6). Histopathological diagnosis based on hepatic needle biopsy was chronic active hepatitis with diffuse infiltration of lymphocyte-dominant inflammatory cells, bridging necrosis, intercellular fibrosis in a limited region, and with ballooning, degeneration, and/or necrosis of the hepatic cells. A job-related cause was suspected and 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123), which has been proven to cause acute hepatitis in humans, was detected in a dry-cleaning solvent by gas chromatography-mass spectrometry analysis. A job simulation experiment suggested that the concentration of the patient's exposure to HCFC-123 exceeded 1,000 ppm during the busiest work period, which was sufficiently high to induce severe liver damage.

Relationship between the blood coagulation-fibrinolysis system and the subclinical indicators of arteriosclerosis in a healthy male population

Nishiwaki Yuji, Takebayashi Toru, Omae Kazuyuki, Ishizuka Chizuru, Nomiyama Tetsuo, Sakurai Haruhiko

Journal of Epidemiology 10 （ 1 ） 34 - 41 2000年

研究論文（学術雑誌）, 共著, ISSN 0917-5040

A cross-sectional observation was performed to assess the relationship between the coagulation-fibrinolysis system and the subclinical indicators of arteriosclerosis in a healthy male population. Subjects were 445 workers (18.9-49.4, Av.36.2yrs) in viscose rayon manufacturing factories in Japan. Coagulation-fibrinolysis parameters determined were D-dimer(DD), thrombin antithrombinlï ï complex (TAT), tissue plasminogen activator fTPA), and plasminogen activator inhibitor 1 (PAH). The following indicators of arteriosclerosis were examined; systolic and diastolic blood pressure (SBP, DBP), stiffness parameter of the carotid artery using ultrasound (, ?), pulse wave velocity of the aorta (PWV), and a number of lacunar infarctions from brain MRI. After age-stratification(-29, 30-39, 40+yrs), the subjects were classified into quartiles by coagulation-fibrinolysis parameters. The mean values of SBP and DBP and and PWV , the prevalence of brain infarctions were compared across these quartiles by means of analysis of variance, chi-square test, respectively. Multivariate analysis was also employed to adjust other risk factors. In conclusion, SBP and DBP and, ?, PWV were elevated by increase of PAH, TAT, respectively, in the 40+ years group even after adjustment for other possible risk factors. DD had no relation to any of the indicators of arteriosclerosis. None of the coagulation-fibrinolysis parameters had any relation to brain infarctions.

Difference by instructional set in stabilometry

Nishiwaki Yuji, Takebayashi Toru, Imai Azusa, Yamamoto Masahiko, Omae Kazuyuki

Journal of Vestibular Research: Equilibrium and Orientation 10 （ 3 ） 157 - 161 2000年

研究論文（学術雑誌）, 共著, ISSN 0957-4271

There is no standard for the awareness of standing posture in stabilometry, yet little research addressing the matter has been carried out. In the present study, we evaluated the influence of different instructional sets during, a test on stabilometry. Stabilometry was performed on 349 male subjects. Two different instructions were prepared for the subjects regarding the awareness of their standing posture. These instructions were a) 'Please relax when you stand' (R-standing), and b) 'Please make an effort to minimize your body sway' (E-standing). Subjects were classified into four groups according to the combination of these instructions they received. For the five body sway parameters, a comparison between R-standing and E-standing was performed, controlling for possible confounders such as age, height, body weight, educational history, alcohol consumption, and smoking status. The sway length in E-standing was larger than that in R-standing, even after the adjustment for possible confounders. Our results indicate that the difference in the instructional set caused a significant measurement bias. Thorough-going unification of instructions for the stabilometry should be recommended when stabilometry is performed in an epidemiological investigation.

第6次改定日本人の栄養所要量─食事摂取基準：フッ素

武林亨

臨床栄養 95 （ 6 ） 716-719 1999年11月

研究論文（学術雑誌）, 単著

代替フロンによる急性肝炎─2,2-ジクロロ-1,1,1-トリフルオロエタン（HCFC-123）の事例─

大前和幸，武林亨

医学のあゆみ 191 （ 2 ） 172-173 1999年10月

研究論文（学術雑誌）, 共著

Occupational exposure limits based on biological monitoring : the Japan Society for Occupational Health

Omae Kazuyuki, Takebayashi Toru, Sakurai Haruhiko

International Archieves of Occupational and Environmental Health 72 （ 4 ） 271-273 1999年07月

研究論文（学術雑誌）, 共著

Stabilometry in epidemiological use - Measurement bias by different instructions -

Nishiwaki Yuji, Imai Azusa, Takebayashi Toru, Nishiwaki Noriko, Omae Kazuyuki

Journal of Occupational Health 41 （ 2 ） 129 - 130 1999年04月

研究論文（学術雑誌）, 共著, ISSN 1341-9145

Animal models of asthma and chronic bronchitis

Drazen J. M., Takebayashi T., Long N. C., De Sanctis G. T., Shore S. A.

Clinical and Experimental Allergy, Supplement 29 （ 2 ） 37 - 47 1999年

研究論文（学術雑誌）, 共著, ISSN 0960-2178

Human asthma is characterized by three critical phenotypic traits: intermittent reversible airway obstruction, airway hyperresponsiveness and airway inflammation. In animal models of asthma, airway hyperresponsiveness is an important feature. This trait is characterized by an exaggerated bronchoconstrictor response that would have little physiological consequence in an otherwise unaffected or normal individual. In this article we explore two distinct facets of airway responsiveness. The first is the genetic basis for variations in airway responsiveness that occur in mice in the absence of any specific environmental manipulation. We demonstrate that standard genetic approaches can be successfully applied to the identification of regions of the mouse genome linked to the expression of airway hyperresponsiveness. The second topic addressed in this review is the change in airway responsiveness induced in rats by repeated exposure to sulphur dioxide gas. With daily exposure to high concentrations of sulphur dioxide gas, there is chronic injury and repair of epithelial cells. Over time, rats develop mucous hypersecretion, airway inflammation, increased airway resistance and airway hyperresponsiveness. This model has provided useful information on the mechanisms underlying the pathophysiological events that typify the chronic bronchitis in humans.

Meso-2,3-dimercaptosuccinic acid（DMSA）およびその誘導体の鉛中毒治療効果

大前和幸，武林亨

産業医学ジャーナル 22 （ 6 ） 77-80 1999年

研究論文（学術雑誌）, 共著

2,2-ジクロロ-1,1,1-トリフルオロエタン (HCFC-123) による健康影響

大前和幸，武林亨

産業医学ジャーナル 21 （ 6 ） 90-91 1998年11月

研究論文（学術雑誌）, 共著

Toxicity of silicon compounds in semiconductor industries

Nakashima Hiroshi, Omae Kazuyuki, Takebayashi Toru, Ishizuka Chizuru, Uemura Takamoto

Journal of Occupational Health 40 （ 4 ） 270 - 275 1998年10月

研究論文（学術雑誌）, 共著, ISSN 1341-9145

The toxicities of silane (SiH₄), tetraethoxysilane (Si(OC₂H₅)₄, TEOS) and dichlorosilane (SiH₂Cl₂, DCS) were reviewed in order to compare the toxicological properties of silicon compounds used in the semiconductor industry. Silane and TEOS showed similar toxicities, characterized by nephrotoxicity. Mice subjected to silane (2500, 5000 and 10000 ppm) or TEOS (1000 ppm) acute exposure developed acute tubular necrosis. Tubulo- interstitial nephritis was seen in mice which were subjected to an acute inhalation study and survived 2 wk of the observation period or those subjected to subacute inhalation studies of TEOS (100 and 200 ppm for 2 or 4 wk). Silane and TEOS, however, differed in the concentration at which they showed signs of toxicity. This may be due to their solubility in water and other metabolic factors, but their metabolic pathways have not yet been elucidated. TEOS injured nasal mucosa (1000 ppm for 2 h or more and 50, 100 and 200 ppm for 2 or 4 wk). It was observed at a lower concentration than nephrotoxicity in the 50 and 100 ppm subacute inhalation study. On the other hand, silane caused nasal mucosal lesions only at 5000 or 10000 ppm for acute inhalation, and those of subacute inhalation were mild (1000 ppm for 2 or 4 wk). DCS showed another type of adverse effect. It was an irritant and/or a corrosive agent to the respiratory tract in the acute (64 ppm for 1,2, 4 or 8 h) and subacute (32 ppm for 2 or 4 wk) inhalation study. The fate of DCS in air was also studied and it was shown to form small particles including silicon and chlorine (CI) atoms. CI seems to play an important role in the toxicity of DCS.

Toxicity of silicon compounds in semiconductor industries

Nakashima Hiroshi, Omae Kazuyuki, Takebayashi Toru, Ishizuka Chizuru, Uemura Takamoto

Journal of Occupational Health 40 （ 4 ） 270-275 1998年10月

研究論文（学術雑誌）, 共著

Exposure to 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123) and acute liver dysfunction

Takebayashi Toru, Kabe Isamu, Endo Yu'ichi, Tanaka Shigeru, Miyauchi Hiroyuki, Nozi Kazuko, Imamiya Shun Ichiro, Takahashi Ken, Omae Kazuyuki

Journal of Occupational Health 40 （ 4 ） 334 - 338 1998年10月

研究論文（学術雑誌）, 共著, ISSN 1341-9145

Acute liver dysfunction has been reported among workers repeatedly exposed to 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123), a substitute for trichlorofluoromethane. Causality between occupational exposure to HCFC-123 and liver dysfunction was examined. Levels of exposure to HCFC-123 were estimated retrospectively by reproducing working conditions and by a job record survey. Health surveillance, including liver function and subjective symptoms, was done when two workers first complained of ill health. The mean HCFC-123 concentration in air was more than 200 ppm with a peak concentration of about 1,000 ppm in a processing area where HCFC-123 was used. HCFC-123 of 18-24 ppm was detected in the adjunct areas where HCFC-123 vapor was not generated. Workers (n=14) were then classified into high (n=5) and low (n=9) exposure groups according to the estimated exposure level, which was confirmed by determination of urinary trifluoroacetic acid. Mean serum AST and ALT levels were 236 IU// and 476 IU// among the high-exposed workers, and exceeded 500 IU// in three workers. Various types of symptoms involving the central nervous system and digestive organs, and irritation of the mucous membrane, were also experienced. The degree and prevalence of these health effects were higher in the high exposure group, which indicates the exposure- effect and exposure-response relationships. The consistency and temporality of the relationship between HCFC-123 exposure and the observed health effects were also confirmed. We conclude that repeated exposure to high concentrations of HCFC-123 for no more than five weeks causes acute severe liver dysfunction with various symptoms in humans. Biological plausibility must be clarified to confirm the causality.

Environmental and biological monitoring of 2,2-dichloro-1,1,1- trifluoroethane (HCFC-123)

Tanaka Shigeru, Kabe Isamu, Takebayashi Toru, Endo Yu'ichi, Miyauchi Hiroyuki, Nozi Kazuko, Takahashi Ken, Seki Yukio, Omae Kazuyuki

Journal of Occupational Health 40 （ 4 ） 348 - 349 1998年10月

研究論文（学術雑誌）, 共著, ISSN 1341-9145

Role of tachykinins in airway responses to ozone in rats

Takebayashi Toru, Abraham Joseph, Murthy G. G Krishna, Lilly Craig, Rodger Ian, Shore Stephanie A.

Journal of Applied Physiology 85 （ 2 ） 442 - 450 1998年08月

研究論文（学術雑誌）, 共著, ISSN 8750-7587

Previous studies that used neonatal capsaicin (Cap) treatment to ablate C fibers indicate that C fibers act to inhibit lung damage and airway hyperresponsiveness after ozone (O₃) exposure in rats. The purpose of this study was to determine 1) the role of tachykinins in these protective effects and 2) whether differences in minute ventilation (V̇E) during O₃ exposure might account for the effect of Cap. In the first study, male Sprague-Dawley rats were exposed to 1 part/million O₃ or air for 3 h. Four hours later, a bronchoalveolar lavage (BAL) was performed or airway responsiveness was measured. Rats were treated with CP-99994 and SR-48968, selective neurokinin- 1-and -2-receptor antagonists, respectively, or with vehicle (Veh). O₃ caused an increase in the number of neutrophils recovered from BAL fluid in both the Veh-treated and tachykinin-receptor antagonist (TKRA)-treated rats, but the number of neutrophils was approximately twofold greater in the TKRA- treated rats. In contrast, TKRA treatment had no effect on baseline pulmonary mechanics or airway responsiveness. After O₃ exposure, the number of neutrophils in BAL fluid was also greater in Cap- than in Veh-treated rats. O₃ reduced V̇E in both Veh- and Cap-treated rats, but the response was greater (reduction of 44.7 ± 3.7 vs. 27.8 ± 6.8%) and occurred earlier (10 vs. 70 min) in Cap- than in Veh-treated rats (P < 0.02). These results suggest that tachykinins mediate protective effects of C fibers against O₃- induced lung inflammation. The results also indicate that the more pronounced effect of O₃ on BAL neutrophils in Cap-treated rats is not the result of a greater inhaled dose of O₃ resulting from greater V̇E.

Acute liver dysfunction among workers exposed to 2,2-dichloro-1,1,1- trifluoroethane (HCFC-123)

Takebayashi Toru, Kabe Isamu, Endo Yu'ichi, Tanaka Shigeru, Miyauchi Hiroyuki, Nozi Kazuko, Takahashi Ken, Omae Kazuyuki

Journal of Occupational Health 40 （ 3 ） 169 - 170 1998年07月

研究論文（学術雑誌）, 共著, ISSN 1341-9145

Cross-sectional observation of the effects of carbon disulfide on arteriosclerosis in rayon manufacturing workers

Omae Kazuyuki, Takebayashi Toru, Nomiyama Tetsuo, Ishizuka Chizuru, Nakashima Hiroshi, Uemura Takamoto, Tanaka Shigeru, Yamauchi Tsuneyuki, O'uchi T, Horichi T, Sakurai Haruhiko

Occupational and Environmental Medicine 55 （ 7 ） 468-472 1998年07月

研究論文（学術雑誌）, 共著

Cross-sectional observation of the effects of carbon disulfide on the nervous system, endocrine system, and subjective symptoms in rayon manufacturing workers

Takebayashi Toru, Omae Kazuyuki, Ishizuka Chizuru, Nomiyama Tetsuo, Sakurai Haruhiko

Occupational and Environmental Medicine 55 （ 7 ） 473-479 1998年07月

研究論文（学術雑誌）, 共著

Cross sectional observation of the effects of carbon disulphide on the nervous system, endocrine system, and subjective symptoms in rayon manufacturing workers

Takebayashi Toru, Omae Kazuyuki, Ishizuka Chizuru, Nomiyama Tetsuo, Sakurai Haruhiko

Occupational and Environmental Medicine 55 （ 7 ） 473 - 479 1998年

研究論文（学術雑誌）, 共著, ISSN 1351-0711

Objectives - A prospective cohort study was initiated to clarify whether the current level of exposure to carbon disulphide (CS₂) is low enough to prevent occurrence of subclinical health impairments or to ameliorate health effects due to past high exposure. This paper describes the effects of exposure to CS₂ on the nervous and endocrine systems, and the subjective symptoms in a baseline observation. Methods - The effects were evaluated of CS₂ on the median nerve conduction velocity, neurobehavioural and psychological tests, and subjective symptoms related to solvents in 432 male workers exposed to CS₂ and 402 reference workers from 11 rayon factories in Japan. Adjustment was made for potential confounding factors such as age or alcohol drinking. Exposure to CS₂ was either dichotomised or categorised into three groups by job type. Results - Reductions were observed in motor (- 1.9 m/s) and sensory (-0.91 m/s for orthodromic and -1.1 m/s for antidromic) nerve conduction velocities in the workers exposed to CS₂ at the spinning and refining processes. Small but significant increases were found in self rated depression scale score and decrease in digit span (backward) in the workers exposed to CS₂. Of 54 subjective symptoms many were increased- namely, heavy feeling in the head, light headedness, fainting after suddenly standing up, tremor, dullnes, and increased sensitivity of skin in the extremities, reduced grasping power, reduced sexual desire, and increased rough skin. The endocrinological indicator-the concentration of glycosylated haemoglobin-was also increased in the workers exposed to CS₂. Conclusions - Subclinical effects on the nervous system and on glucose metabolism were found in the workers exposed to CS₂. One interpretation is that relatively higher exposure to CS₂ in the past may induce these, but the effects are still not entirely ameliorated under the current exposure to CS₂. Another possibility is that the current exposure to CS₂ may cause these positive findings. A follow up observation is necessary to clarify these questions.

Cross sectional observation of the effects of carbon disulphide on arteriosclerosis in rayon manufacturing workers

Omae Kazuyuki, Takebayashi Toru, Nomiyama Tetsuo, Ishizuka Chizuru, Nakashima Hiroshi, Uemura Takamoto, Tanaka Shigeru, Yamauchi Tsuneyuki, O'Uchi Toshihiro, Horichi Yasushi, Sakurai Haruhiko

Occupational and Environmental Medicine 55 （ 7 ） 468 - 472 1998年

研究論文（学術雑誌）, 共著, ISSN 1351-0711

Objective - A prospective cohort study was designed no clarify the relations between occupational exposure to carbon disulphide (CS₂) and its effects on arteriosclerosis in workers in 11 Japanese rayon manufacturing factories. This report is a cross sectional baseline observation in the first study year. Methods - Study subjects were 432 male rayon workers (mean (range) age 35.5 (19.1-47.8); duration of exposure 13.4 (0.3-29.0)) and 402 male referent workers (age 35.8 (18.9-49.8)). Exposure to CS₂ was assessed by determining the concentration of 2-thiothiazolidine-4-carboxylic acid (TTCA) in urine. Mean (SD) TTCA was 3.42 (2.73) mg/g creatinine (Cr) (n=422). About a quarter of the urine samples were >5 mg/g Cr, a biological exposure index recommended by the American Conference of Governmental Industrial Hygienists. Health effects on arteriosclerosis were evaluated by measuring blood pressure, serum lipids, pulse wave velocity of the aortas stiffness and blood flow of the carotid artery, and blood coagulation and fibrinolysis indices, and by use of brain magnetic resonance imaging, electrocardiogram (at rest and after exercise), ophthalmograph, and Rose's questionnaire. Information on potential confounding factors was collected by self administered questionnaire. Results - Prevalence of microaneurysm of the retinal artery was significantly higher in workers exposed to CS₂ (8.1%) than in referent workers (3.4%), and increased with age. Other examinations did not show any differences between the two groups even after allowance for confounding factors. Conclusions - Significant effects of CS₂ on arteriosclerosis were not found in current rayon manufacturing workers, with the exception of induction of microaneurysm of the retinal artery.

Effects of intratracheally administered indium phosphide on male fischer 344 rats

Uemura Takamoto, Oda Kenichi, Omae Kazuyuki, Takebayashi Toru, Nomiyama Tetsuo, Ishizuka Chizuru, Hosoda Kanae, Sakurai Haruhiko, Yamazaki Kazuto, Kabe Isamu

Journal of Occupational Health 39 （ 3 ） 205 - 210 1997年07月

研究論文（学術雑誌）, 共著, ISSN 1341-9145

Objective - To examine the effects of intratracheally administered indium phosphide (InP) and distribution of indium on male Fischer 344 rats. Materials and methods - Rats were intratracheally given 0, 1, 10 or 100 mg/kg of InP with a mean diameter of 0.8 μm and observed for 1 and 7 days. The bronchoalveolar lavage fluid (BALF) was examined biochemically and cytologically. Serum biochemical, hematological and histopathological examinations were done, and the indium concentration in organs and serum was determined. Findings - The number of neutrophils in BALF remarkably increased in a dose-effect manner 1 and 7 days after administration and InP particles were phagocytized in the macrophages. Total protein (TP), lactate dehydrogenase (LDH), total phospholipid (TPL) and total cholesterol (T-Cho) in BALF showed a clear dose-effect relationship 7 days after administration. Indium was detected in the liver and spleen and increased in a dose-related manner on the next day and 7 days after administration. Serum indium was detected in the group given more than 10 mg/kg but did not reveal a dose relationship. Histopathological examination of the lungs showed phagocytized InP particles in the macrophages and the migration of neutrophiles in the alveoli. InP particles remained in the bronchioles and alveoli until 7 days after. No histopathological changes were detected in the liver or spleen . A hematological study did not reveal significant findings. Interpretation - Intratracheally administered InP particles cause pulmonary inflammation and those particles remain in the lower airways for at least 7 days. Phagocytosis of macrophages may contribute to their disposal and distribution to the liver and spleen. Further study is required with particles with a lower toxic activity than InP and with the same particle size as the InP used in this study, to clarify their specific toxicity. Simultaneously longer observation is needed to assess toxicity in the other organs after distribution.

A simple method for carbon disulfide monitoring using a diffusive sampler, thermal desorption and a stain tube

Tanaka Shigeru, Yamauchi Tuneyuki, Takebayashi Toru, Omae Kazuyuki, Seki Yukio

Industrial Health 35 （ 4 ） 474 - 479 1997年

研究論文（学術雑誌）, 共著, ISSN 0019-8366

A simple sampling and analytical method for monitoring carbon disulfide (CS₂) vapor was investigated to assess exposure to low levels of CS₂ in a viscose rayon factory. CS₂ vapor was adsorbed on polymer beads (poly (2,6- diphenyl-p-phenylene oxide)) packed in a diffusive sampling tube. The sampling tube was heated at 180°C for 7 min using a Daily Exposure Limit Test Apparatus, and thermally desorbed CS₂ was measured by a stain tube for CS₂. In laboratory experiments, the indicated CS₂ levels measured by this method were highly correlated with calibrated CS₂ concentrations (1-40 ppm), exposure duration (1-8 hr) and cumulative exposure levels. The CS₂ values were stable up to 7 days after sampling when the diffusive tubes were stored at 4°C and 20°C. The effects of relative humidity, wind velocity and hydrogen sulfide on the measured values were negligible. In a field survey, 65 workers in a viscose rayon factory wore both the diffusive sampling tube and a commercially available 3M 3500 organic vapor monitor on their collar during their 8-hr work period. CS₂ concentrations obtained by the two methods were comparable and the correlation coefficient was 0.931. This method proved to be useful in determining the concentrations of CS₂ to which workers were exposed.

Respiratory diseases and working in a copper or an aluminum product plant. A case control study using medical records

Kabe Isamu, Endo Yuichi, Takahashi Ken, Takebayashi Toru, Omae Kazuyuki, Sakurai Haruhiko

J Occup Health 39 343-344 1997年

研究論文（学術雑誌）, 共著

産業保健の倫理学的側面

武林亨

産業医学ジャーナル 19 （ 6 ） 69-73 1996年11月

研究論文（学術雑誌）, 単著

A comparison of U.S. and Japanese occupational exposure limits for chemical substances and biological monitoring values

Takebayashi Toru, Omae Kazuyuki, Sherwood R. J.

Applied Occupational and Environmental Hygiene 11 （ 5 ） 457 - 462 1996年05月

研究論文（学術雑誌）, 共著, ISSN 1047-322X

This article compares current values for occupational exposure criteria in Japan and the United States and briefly describes the Japanese organization. The values recommended by the committee of the Japan Society for Occupational Health (JSOH) correspond fairly closely with those of the American Conference of Governmental Industrial Hygienists (ACGIH®) threshold limit value (TLV®) and biological exposure index (BEI(TM)) committees, perhaps because much of the information is drawn from the same database. For only six substances do the limits differ by more than a factor of 10, while for 121 substances the limits differ by less than a factor of 2. For 28 substances the TLV exceeds the JSOH occupational exposure limit (OEL) by a factor of between 2 and 10, while for 18 the TLV is correspondingly less than the JSOH OEL. Provisional values are given, or changes proposed, for 29 substances. The principal biological limits for mercury are identical, while those for lead and hexane differ by less than a factor of 2. Classification of carcinogens differs slightly, but the numbers of proven human carcinogens are similar, as are the total numbers considered suspect.

Relationship between acetone exposure concentration and health effects in acetate fiber plant workers

Satoh Toshihiko, Omae Kazuyuki, Nakashima Hiroshi, Takebayashi Toru, Matsumura Hiroshi, Kawai Toshio, Nakaza Masahiro, Sakurai Haruhiko

International Archives of Occupational and Environmental Health 68 （ 3 ） 147 - 153 1996年03月

研究論文（学術雑誌）, 共著, ISSN 0340-0131

In order to clarify the effects of acetone (AC) exposure on health, a cross-sectional study was carried out in 110 male AC-exposed and 67 male nonexposed shift workers. The AC workers ranged in age from 18.7 to 56.8 years (mean: 37.6 years) and in length of AC exposure from 0.5 to 34.3 years (mean: 14.9 years). The nonexposed workers ranged in age from 20.7 to 57.5 years (mean: 41.9 years). AC exposure levels assessed by personal passive monitors and biological monitoring indices measured at the end of the workshift were 19.6-1018 ppm in the breathing zone (AC-E, mean: 364 ppm), 2.5-422 ppm in alveolar air (AC-A, mean: 97.3 ppm) 4-220 mg/l in blood (AC-B, mean 66.0 ppm), and 0.75-170 mg/l in urine (AC-U, mean: 37.8 mg/l). Symptoms at the end of the workshift with good exposure-response relationships were eye irritation, tearing, and acetone odor, and symptoms within the previous 6 months with good exposure-response relationships were heavy, vague, or faint feeling in the head, nausea, loss of weight, and slow healing of an external wound. In the 30-44 year age range, simple reaction time and digit span scores in a short computerized neurobehavioral test battery were significantly lower in AC workers, but exposure-response relationships were not clear. Manifest Anxiety Scale scores, Self-rating Depression Scale scores, R-R interval variation on the ECG, hematological examinations, serum biochemistry examinations for liver function, and phagocytic activity of peripheral neutrophils did not show any AC-related differences between the two groups. In view of the reported findings, the current occupational exposure limit of 750 ppm recommended by many governmental and academic associations seems to be too high to prevent the health effects of AC observed in this study.

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Acute and subacute inhalation toxicity of dichlorosilane in male ICR mice

Nakashima H., Omae K., Takebayashi T., Ishizuka C., Sakurai H., Yamazaki K., Nakaza M., Shibata T., Kudo M., Koshi S.

Archives of Toxicology 70 （ 3-4 ） 218 - 223 1996年01月

研究論文（学術雑誌）, 共著, ISSN 0340-5761

Using male ICR mice, the LC₅₀ and acute and subacute inhalation toxicity of dichlorosilane (SiH₂Cl₂, DCS) and the fate of DCS released into the air were investigated. DCS resolved and minute particles including silicon and chloride were observed, when DCS was released into the air. Most particles were under 1 micron in diameter. The CL₅₀ of DCS at 4-h exposure was 144 ppm (nominal concentration). In the acute inhalation study, ten mice in each group were exposed to 64 ppm (nominal concentration) DCS for 1, 2, 4 or 8 h. Body weight loss, wheezing and piloerection were observed in mice exposed for 2 h or more. Histopathologically, injury to the nasal mucosa and trachea were observed in all exposed mice. Mice exposed to 32 ppm (nominal concentration) DCS for 2 or 4 weeks also exhibited depression of body weight gain, wheezing and piloerection. Squamous metaplasia of the nasal mucosa and tracheal epithelium was observed in both 2- and 4-week exposure groups. Exposure to DCS was irritant or corrosive to the respiratory tract with both acute and subacute inhalation. Apart from silane (SiH₄), toxic effects of DCS seem to be characterized by chloride compounds derived from DCS. © 1996 Springer-Verlag.

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Acetone excretion into urine of workers exposed to acetone in acetate fiber plants

Satoh Toshihiko, Omae Kazuyuki, Takebayashi Toru, Nakashima Hiroshi, Higashi Toshiaki, Sakurai Haruhiko

International Archives of Occupational and Environmental Health 67 （ 2 ） 131 - 134 1995年03月

研究論文（学術雑誌）, 共著, ISSN 0340-0131

To develop a proper protocol for biological exposure monitoring of acetone, we evaluated whether exposure to acetone on the previous day affects the biological monitoring value at the end of a work day. One hundred and ten male workers exposed to acetone in three acetate fiber manufacturing plants were monitored using a liquid passive sampler on two consecutive working days after 2 days without exposure. Urine samples were collected at the start of the workshift and the end of the shift on both days for each subject. For ten exposed workers urine samples were collected approximately every 2 h during and after the first working day until the following morning. Acetone concentrations in urine (Cu) at the start of the first working day were 1.3 ± 2.4 (range: ND-14.1) mg/l in nonexposed workers and 2.4 ± 5.6 (range: ND-40.3) mg/l in exposed workers. The urinary acetone concentration at the beginning of the second working day indicated that urinary levels of acetone do not decline to background level by the following morning when exposure concentration exceeds 300 ppm. However, linear regression analysis demonstrated that the relationship between environmental exposure level and urine level was similar on the 1st day and the 2nd day. Thus, although urine acetone levels did not return completely to baseline after high exposures, under the present exposure levels the exposure on the previous day did not significantly affect urinary acetone at the end of the workshift of the next day. © 1995 Springer-Verlag.

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No-observed-effect level of diborane on the respiratory organs of male mice in acute and subacute inhalation experiments

Nomiyama T., Omae K., Uemura T., Nakashima H., Takebayashi T., Ishizuka C., Yamazaki K., Sakurai H.

Journal of Occupational Health 37 （ 3 ） 157 - 160 1995年

研究論文（学術雑誌）, 共著, ISSN 1341-0725

In order to clarify the acute and subacute toxicity of diborane (B₂H₆, CAS: 19287-45-7) at low concentrations, male ICR mice were exposed to diborane for 1, 2, 4 or 8 h at concentrations of 1 or 5 ppm (phase I study), and for 6 h/day, 5 days/wk, over 2 or 4 wk at concentrations of 0.2 or 0.7 ppm (phase II study). Hematological and biochemical tests, and histopathological examinations of the cornea, nasal mucosa, respiratory tract and lung were carried out. All mice in both studies survived until they were sacrificed. In the phase I study, lung weight increased significantly in mice exposed to 5 ppm of diborane for 8 h. Histopathologically diffuse panbronchiolitis-like lesion was observed in mice exposed to 5 ppm of diborane for 2, 4 or 8 h. In the phase II study, slight infiltration of polymorphous neutrophil was observed mainly in the peribronchiolar region in mice exposed to 0.2 ppm or 0.7 ppm of diborane for 2 or 4 wk. In both studies, hematological and biochemical examinations failed to reveal any exposure-related changes. These results suggest that no-observed-effect level of diborane inhalation on the respiratory organs were 1 ppm in acute exposure, but 0.2 ppm of diborane inhalation for 2 or 4 wk seems to be unsafe.

No-effect level of subacute tetraethoxysilane inhalation on the mouse kidney

Omae K., Nakashima H., Takebayashi T., Uemura T., Ishizuka C., Yamazaki K., Sakurai H.

Journal of Occupational Health 37 （ 1 ） 1 - 4 1995年

研究論文（学術雑誌）, 共著, ISSN 1341-0725

To determine safe exposure levels of tetraethoxysilane (TEOS) in the kidney, groups of male ICR mice (SPF grade) containing 10 animals each were exposed to TEOS, 100 ppm or 50 ppm, for 6 hours/day, 5 days/week, for 2 or 4 weeks. Tubulointerstitial nephritis developed in mice exposed to 100 ppm for 2 and 4 weeks, but no kidney lesions or renal function changes were observed in mice exposed to 50 ppm. However, histopathological changes were detected in the nasal mucosa of mice exposed to 50 ppm TEOS. These results indicate that the occupational exposure level for TEOS should be strictly maintained below the current recommended exposure limit, 10 ppm, set by many countries and academic associations, and that renal tubular function of TEOS-exposed workers should be assessed and monitored for a long period.

Acute inhalation toxicity of high concentrations of silane in male ICR mice

Takebayashi Toru

Archives of Toxicology 67 （ 1 ） 55 - 60 1993年01月

研究論文（学術雑誌）, 単著, ISSN 0340-5761

In order to examine the toxicity of silane, male ICR mice were exposed to silane for 30 min (n=8), 1 or 4 h (n=12) at concentrations of 2500, 5000, 7500 (30-min experiment only) or 10000 ppm. In the 1- and 4-h experiments, 12 mice were divided into two sub-groups: four for 2-day observation and eight for 2-week observation. The mortality was six deaths out of eight mice exposed to 10000 ppm for 4 h. No deaths occurred in any of the other experiments. In the mice sacrificed 2 days after the exposure, acute renal tubular necrosis was observed at 10000 ppm (1-h exposure) or at 2500 ppm or more (4-h exposure). Reduction in body weight, increase in relative kidney weight and blood urea nitrogen (BUN) level, and splenic atrophy and inflammatory changes of the nasal mucosa were also seen in the 10000 ppm-4 h exposure group. In the mice sacrificed 2 weeks after the exposure, tubulo-interstitial nephritis (TIN) developed at 7500 ppm or more (30-min exposure) or at 5000 ppm or more (1- and 4-h exposure). BUN increased in a dose-dependent manner, and BUN in TIN positive mice was significantly higher than that in TIN negative mice (1- and 4-h exposure). No histopathological changes were observed in the glomeruli. These results indicate that the LC₅₀ of silane in mice is between 5000 and 10000 ppm for 4-h exposure and is greater than 10000 ppm for 1-h or 30-min exposure. The target site of silane toxicity is the renal tubule, and the no-observed-effect levels of silane for acute inhalation exposure in mice are 1000 ppm for 4-h exposure (from the previous report of our research group), 2500 ppm for 1-h exposure and 5000 ppm for 30-min exposure. © 1993 Springer-Verlag.

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Evaluation of δ-aminolaevulinic acid in blood of workers exposed to lead

Takebayashi T., Omae K., Hosoda K., Satoh T., Hamaguchi T., Sakurai H.

British Journal of Industrial Medicine 50 （ 1 ） 49 - 54 1993年

研究論文（学術雑誌）, 共著, ISSN 0007-1072

Exposure-effect and exposure-response relation between exposure to lead and δ-aminolaevulinic acid concentration in blood (ALA-B) were examined in 238 male workers exposed to lead. Concentrations of ALA-B ranged from 26 to 352 μg/l and lead concentrations in blood (Pb-B) from 7.1 to 86.0 μg/dl. Concentrations of ALA-B correlated closely with concentrations of Pb-B (r = 0.74), and increased ALA-B concentration occurred at Pb-B concentrations of around 30 μg/dl. Exposure-response curves indicated that the 50 percentile response doses were roughly 30, 40, and 50 μg/dl Pb-B when cut off points of ALA-B were set at 50, 60, and 70 μg/l respectively. The sensitivity and specificity of measurements of ALA-B concentrations for health screening were sufficiently high when the health based exposure limits of lead were set at 30-50 μg/dl. Moreover, a pronounced increase in ALA-B concentrations occurred when the inhibition rate of erythrocyte ALA dehydratase exceeded 85%. These findings suggest that ALA-B is a useful indicator for assessing the early effects of exposure to lead on haem biosynthesis.

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