School of Medicine, Department of Preventive Medicine and Public Health (Shinanomachi)


Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured) (N/A)

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Career 【 Display / hide

  • 2008.04

    The University of Tokyo, 医学系研究科公共健康医学専攻生物統計学, 助教

  • 2012.05

    National Institute for Environmental Studies, 環境健康研究センター環境疫学, 研究員

Academic Background 【 Display / hide

  • 2000.04

    The University of Tokyo, 医学部, 健康科学看護学科

    日本, University, Graduated

  • 2004.04

    The University of Tokyo, 医学系研究科, 健康科学看護学専攻

    日本, Graduate School, Completed, Master's course

  • 2006.04

    The University of Tokyo, 医学系研究科, 健康科学看護学専攻

    日本, Graduate School, Withdrawal before completion, Doctoral course

Academic Degrees 【 Display / hide

  • 修士(保健学), The University of Tokyo

  • 学士(保健学), The University of Tokyo

  • 博士(保健学), The University of Tokyo, Dissertation


Research Areas 【 Display / hide

  • Epidemiology and preventive medicine

  • Statistical science

  • Hygiene and public health

Research Keywords 【 Display / hide

  • Biostatistics


Books 【 Display / hide

Papers 【 Display / hide

  • Association between blood manganese level during pregnancy and birth size: The Japan environment and children's study (JECS)

    Yamamoto M., Sakurai K., Eguchi A., Yamazaki S., Nakayama S., Isobe T., Takeuchi A., Sato T., Hata A., Mori C., Nitta H., Ohya Y., Kishi R., Yaegashi N., Hashimoto K., Ito S., Yamagata Z., Inadera H., Kamijima M., Nakayama T., Iso H., Shima M., Hirooka Y., Suganuma N., Kusuhara K., Katoh T.

    Environmental Research (Environmental Research)     117 - 126 2019.05

    ISSN  00139351

     View Summary

    © 2019 The Authors Background: Manganese (Mn) is both an essential element and a potential toxicant. Although a few studies have suggested a nonlinear relationship between the maternal whole blood Mn level at delivery and infant birth weight, little is known about the effects of Mn levels during pregnancy on fetal growth, particularly with regard to sex-specific differences. Methods: In this nationwide birth cohort study, we examined the association of maternal blood Mn level during pregnancy with infant birth weight, length, and head circumference in 16,473 mother–infant pairs. Pregnant women living in 15 regions across Japan were recruited between January 2011 and March 2014. The analysis of birth size (8,484 males and 7,989 females) was conducted using a nonlinear spline, followed by the use of quadratic regression or linear regression models. The analysis of small-for-gestational-age (SGA) (6,962 males and 6,528 females born vaginally) was conducted using multivariate logistic regression. Additionally, subgroup analysis was conducted according to the timing of blood sampling. Results: The median maternal blood Mn level during pregnancy (i.e., 2nd and 3rd trimesters) was 16.2 µg/L (range, 4.3–44.5 µg/L). A positive linear association between the log blood Mn level and head circumference was observed in both male and female infants. However, a nonlinear relationship between the log blood Mn level and birth weight was observed only in male infants, such that the birth weight increased up to a blood Mn level of 18.6 µg/L. In the subgroup analysis stratified by the timing of maternal blood sampling, this nonlinear relationship was obvious only when sampling was performed in the 3rd trimester. Male infants in the lowest blood Mn level quartile (≤ 13.2 µg/L) faced an increased risk of SGA (odds ratio [95% confidence interval] = 1.35 [1.04–1.74]), as did those in the highest blood Mn level quartile (≥ 21.0 µg/L) when sampling was performed during the 3rd trimester (odds ratio [95% confidence interval] = 1.62 [1.10 to 2.39]), compared to those in the third blood Mn level quartile (the category including 18.6 µg/L). No association of blood Mn level with birth weight was observed among female infants, and blood Mn level was not associated with birth length in either male or female infants. Conclusion: A low blood Mn level during pregnancy or a high blood Mn level during the 3rd trimester was associated with a lower birth weight and increased risk of SGA in male infants, but not in female infants. A low blood Mn level was found to correlate slightly with a small head circumference among infants of both sexes.

  • Does Posterior Cervical Decompression Conducted by Junior Surgeons Affect Clinical Outcomes in the Treatment of Cervical Spondylotic Myelopathy? Results From a Multicenter Study

    Nagoshi N., Iwanami A., Isogai N., Ishikawa M., Nojiri K., Tsuji T., Daimon K., Takeuchi A., Tsuji O., Okada E., Fujita N., Yagi M., Watanabe K., Nakamura M., Matsumoto M., Ishii K., Yamane J.

    Global Spine Journal (Global Spine Journal)  9 ( 1 ) 25 - 31 2019.02

    ISSN  21925682

     View Summary

    © The Author(s) 2018. Study Design: Retrospective multicenter study. Objectives: To evaluate the outcomes of posterior cervical decompression for cervical spondylotic myelopathy (CSM) when performed by board-certified spine (BCS) or non-BCS (NBCS) surgeons. Methods: We reviewed outcomes for 675 patients who underwent surgery for CSM, were followed at least 1 year after surgery, and were assessed preoperatively and at final follow-up by Japanese Orthopaedic Association (JOA) scores and by the visual analog scale (VAS) for the neck. Cervical alignment was assessed on radiographs by C2-C7 angles, and range of motion (ROM) by extension minus flexion C2-C7 angles. We compared outcomes for BCS surgeons, who must meet several requirements, including experience in more than 300 spinal surgeries, and for NBCS surgeons. Results: BCS surgeons performed 432 of 675 laminoplasties. NBCS surgeons were primary in 243 surgeries, of which 187 were directly supervised by a BCS surgeon. BCS surgeons required significantly less time in surgery (98.0 ± 39.5 vs 108.1 ± 49.7 min; P <.01). BCS and NBCS surgeons had comparable perioperative complications rates, and preoperative-to-postoperative changes in JOA scores (2.9 ± 2.1 vs 3.1 ± 2.3; P =.40) and VAS (−1.5 ± 2.9 vs −1.4 ± 2.5; P =.96). Lordotic cervical alignment and ROM were maintained after operations by both groups. Conclusions: Surgical outcomes such as functional recovery, complication rates, and cervical dynamics were comparable between the BCS and NBCS groups. Thus, posterior cervical decompression for CSM is safe and effective when performed by junior surgeons who have been trained and supervised by experienced spine surgeons.

  • Randomized Phase II Trial Comparing Site-Specific Treatment Based on Gene Expression Profiling With Carboplatin and Paclitaxel for Patients With Cancer of Unknown Primary Site

    Hayashi, H., Kurata, T., Takiguchi, Y., Arai, M., Takeda, K., Akiyoshi, K., Matsumoto, K., Onoe, T., Mukai, H., Matsubara, N., Minami, H., Toyoda, M., Onozawa, Y., Ono, A., Fujita, Y., Sakai, K., Koh, Y., Takeuchi, A., Ohashi, Y., Nishio, K. and Nakagawa, K.

    J Clin Oncol (Journal of Clinical Oncology)  37 ( 7 ) JCO1800771 - 579 2019.01

    ISSN  1527-7755

     View Summary

    PURPOSE: Although gene expression profiling is a promising diagnostic technique to determine the tissue of origin for patients with cancer of unknown primary site (CUP), no clinical trial has evaluated yet site-specific therapy directed by this approach compared with empirical chemotherapy. We therefore performed a randomized study to assess whether such site-specific therapy improves outcome compared with empirical chemotherapy in previously untreated patients with CUP. PATIENTS AND METHODS: Comprehensive gene expression profiling was performed by microarray analysis, and an established algorithm was applied to predict tumor origin. Patients with CUP were randomly assigned (1:1) to receive standard site-specific therapy or empirical paclitaxel and carboplatin (PC). The primary end point was 1-year survival rate. RESULTS: One hundred thirty patients were randomly assigned and had sufficient biopsy tissue for molecular analysis. Efficacy analysis was performed for 50 and 51 patients in the site-specific therapy and empirical PC arms, respectively. Cancer types most commonly predicted were pancreatic (21%), gastric (21%), and lymphoma (20%). The 1-year survival rate was 44.0% and 54.9% for site-specific treatment and empirical PC ( P = .264), respectively. Median overall and progression-free survival were 9.8 and 5.1 months, respectively, for site-specific treatment versus 12.5 and 4.8 months for empirical PC ( P = .896 and .550, respectively). Median overall survival (16.7 v 10.6 months; P = .116) and progression-free survival (5.5 v 3.9 months; P = .018) were better for predicted more-responsive than less-responsive tumor types. CONCLUSION: Site-specific treatment that was based on microarray profiling did not result in a significant improvement in 1-year survival compared with empirical PC, although prediction of the original site seemed to be of prognostic value.

  • High-grade trichoblastic carcinoma arising through malignant transformation of trichoblastoma: Immunohistochemical analysis and the expression of p53 and phosphorylated AKT

    Fusumae, T., Tanese, K., Takeuchi, A., Takasugi, A., Kawakita, R., Shiraishi, J. and Yoshida, T.

    J Dermatol 46 ( 1 ) 57 - 60 2019.01

    ISSN  1346-8138

     View Summary

    Trichoblastoma (TB) is a benign cutaneous adnexal neoplasm. The lesion typically presents as a slow-growing, solitary, well-circumscribed nodule measuring up to 3 cm in diameter. On rare occasions, TB causes malignant transformation into an aggressive form described as high-grade trichoblastic carcinoma. Four such cases have been reported to date; all were described as high-grade trichoblastic carcinomas. Here, we describe the case of a 72-year-old Japanese male patient with a rapidly enlarging subcutaneous tumor on his lower back, which was diagnosed as high-grade trichoblastic carcinoma. Histopathologically, the tumor featured both benign and malignant components, and a transition zone between these states was clearly evident. In the immunohistochemical analysis, a malignant component was positive for p53 and showed stronger staining of phospho-RAC-alpha serine/threonine-protein kinase (AKT) Ser473 in comparison with a benign component. These results suggest that loss of p53 function and activation of phosphatidylinositol 3-kinase-AKT signaling pathways played important pathogenic roles in malignant transformation of the present case.

  • Blood mercury, lead, cadmium, manganese and selenium levels in pregnant women and their determinants: the Japan Environment and Children’s Study (JECS)

    Nakayama S., Iwai-Shimada M., Oguri T., Isobe T., Takeuchi A., Kobayashi Y., Michikawa T., Yamazaki S., Nitta H., Kawamoto T., Saito H., Kishi R., Yaegashi N., Hashimoto K., Mori C., Ito S., Yamagata Z., Inadera H., Kamijima M., Nakayama T., Iso H., Shima M., Hirooka Y., Suganuma N., Kusuhara K., Katoh T.

    Journal of Exposure Science and Environmental Epidemiology (Journal of Exposure Science and Environmental Epidemiology)   2019

    ISSN  15590631

     View Summary

    © 2019, The Author(s). The Japan Environment and Children’s Study (JECS) is a birth-cohort study of 100,000 mother–child dyads that aims to investigate the effect of the environment on child health and development. Mercury (Hg), lead (Pb), cadmium (Cd), manganese (Mn) and selenium (Se) are considered to be important co-exposures when examining the effect of other chemical substances on child development. The levels of these elements in the blood of 20,000 randomly selected mid/late-term pregnant women from the whole JECS cohort were analysed using inductively coupled plasma-mass spectrometry. The median concentrations (interquartile ranges) for Pb, Hg, Cd, Mn and Se were 0.63 (0.51–0.78) µg dl −1 , 3.83 (2.70–5.43) µg l −1 , 0.70 (0.52–0.95) µg l −1 , 16.1 (13.2–19.6) µg l −1 and 178 (165–192) µg l −1 , respectively. Hg and Se correlated positively with each other (Spearman’s ρ = 0.287), as did Pb and Cd (ρ = 0.239) and Cd and Mn (ρ = 0.267). The blood Pb levels decreased by 5–10-fold over the past 25 years. The main predictors of the blood levels of each element were fish consumption for Hg, maternal age and non-alcoholic beverage consumption for Pb, maternal age and smoking for Cd, gestational age at sampling for Mn and serum protein levels for Se. These results revealed the historical trends and current predictors of the blood levels of these elements in pregnant Japanese women.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • Occupational Exposure Limits for ethylidene norbornene, ethyleneimine, benomyl, and 2,3-epoxypropyl methacrylate, and classifications on carcinogenicity

    Araki A., Azuma K., Endo G., Endo Y., Fukushima T., Hara K., Hori H., Horie S., Horiguchi H., Ichiba M., Ichihara G., Ikeda M., Ishitake T., Ito A., Ito Y., Iwasawa S., Kakumu T., Kamijima M., Karita K., Katoh T., Kawai T., Kawamoto T., Kumagai S., Kusaka Y., Matsumoto A., Miyagawa M., Miyauchi H., Morimoto Y., Nagano K., Naito H., Nakajima T., Nakano M., Nomiyama T., Okuda H., Okuda M., Omae K., Sakurai H., Sato K., Sobue T., Suwazono Y., Takebayashi T., Takeshita T., Takeuchi A., Takeuchi A., Tanaka M., Tanaka S., Tsukahara T., Tsunoda M., Ueno S., Ueyama J., Umeda Y., Yamamoto K., Yamano Y., Yamauchi T., Yano E.

    Journal of Occupational Health (Journal of Occupational Health)  60 ( 4 ) 333 - 335 2018

    ISSN  13419145

Research Projects of Competitive Funds, etc. 【 Display / hide

  • 小児環境疫学研究に適用するライフコースアプローチの重点的な開発


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 竹内 文乃, Fund for the Promotion of Joint International Research (Home-Returning Researcher Development Research (A)), Principal Investigator

  • 大規模環境疫学研究のためのライフコース統計解析手法の重点的開発と実データ適用


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 竹内 文乃, Grant-in-Aid for Scientific Research (B), Principal Investigator

  • Development life course approach to birth cohort study


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 竹内 文乃, Grant-in-Aid for Young Scientists (B), Principal Investigator

  • 統計数理研究所平成28年度公募型共同利用


    統計数理研究所, Joint research, Principal Investigator

  • 平成28年厚生労働科学研究委託費


    厚生労働省, Health and Labour Sciences Research Grants, Joint research, Co-investigator

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Awards 【 Display / hide

  • 日本疫学会ポスター賞

    2012.01, 日本疫学会

  • 日本計量生物学会奨励賞

    2011.09, 日本計量生物学会


Courses Taught 【 Display / hide











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Courses Previously Taught 【 Display / hide

  • 基礎生物統計学1

    Keio University, 2016, Spring Semester, Major subject, Lecture, Lecturer outside of Keio, 2h, 50people

  • 応用生物統計学

    Keio University, 2016, Autumn Semester, Major subject, Lecture, Lecturer outside of Keio, 2h, 20people

  • 疫学研究の統計的方法

    Keio University, 2016, Spring Semester, Major subject, Lecture, 2h, 30people

  • 基礎生物統計学2

    Keio University, 2016, Spring Semester, Major subject, Lecture, Lecturer outside of Keio, 2h, 50people

  • 基礎生物統計学1

    Keio University, 2015, Spring Semester, Major subject, Lecture, Lecturer outside of Keio, 2h, 70people

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