ANNUAL REPORT OF THE GRADUATE SCHOOL OF
MEDICINE
THE FACULTY OF MEDICINETHE UNIVERSITY OF TOKYOREPORTS FOR THE PERIOD April 2006-March 2007

Introduction
This is the report of the University of Tokyo’s Faculty of Medicine and Graduate School of Medicine forthe year 2006. Here we document each department’s research and education activities.
The University of Tokyo has a historically unique role as the leading force in medicine within Japan. It
is only natural to expect that we well also be in the forefront of medicine worldwide. We take it as our
mission to be an internationally recognized source of important research results, and a center for training
outstanding medical scientists and clinicians.
Throughout the 20th century medicine was dominated by the West, but we are confident that in the 21st
century much greater contributions will come from Asia. In that context the role of Japan, and in particularthat of the Graduate School of Medicine at the University of Tokyo, will become even more important.
Always conscious of our mission, we should continue pursuing our educational and scientific interests
enthusiastically.
As we create the future, let us strive to achieve the best in medical research and teaching.
Nobutaka Hirokawa
Dean, Faculty of medicine and Graduate School of Medicine
The University of Tokyo
March, 2007

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CONTENTS
Introduction
Teaching, Research, Secretarial and Administrative Staffs
Organization Chart
History
The University of Tokyo, Graduate School of Medicine
Molecular Cell Biology
1. Cell Biology and Anatomy ··················································································································
Department of Cell Biology and Anatomy ··························································································
2. Biochemistry and Molecular Biology ··································································································
Department of Molecular Biology ·······································································································
Department of Cellular Signaling ········································································································
Department of Physiological Chemistry and Metabolism ···································································
Functional Biology
1. Physiology ···········································································································································
Department of Integrative Physiology ·································································································
Department of Cellular and Molecular Physiology ·············································································
Department of Neurophysiology ·········································································································
2. Pharmacology ······································································································································
Department of Cellular and Molecular Pharmacology ········································································
Department of Molecular Neurobiology ······························································································
Pathology, Immunology and Microbiology
1. Pathology ·············································································································································
Department of Pathology and Diagnostic Pathology ···········································································
Department of Molecular Pathology ····································································································
2. Microbiology ·······································································································································
Department of Microbiology ···············································································································
Department of Infection Control and Prevention ·················································································
3. Immunology ·········································································································································

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Department of Immunology ·················································································································
Radiology and Biomedical Engineering
1. Radiology ·············································································································································
Department of Radiology ·····················································································································
2. Biomedical Engineering ······················································································································
Department of System Physiology ······································································································
Department of Biosystem Construction & Control ·············································································
Neuroscience
1. Basic Neuroscience ······························································································································
Department of Neuropathology ···········································································································
Department of Neurochemistry ···········································································································
2. Speech and Cognitive Sciences ···········································································································
Department of Speech Science ············································································································
3. Clinical Neuroscience
Department of Neuropsychiatry ···········································································································
Department of Neurology ····················································································································
Department of Neurosurgery ···············································································································
Social Medicine
1. Occupational, Environmental and Preventive Medicine ·····································································
Department of Molecular Preventive Medicine ···················································································
Department of Public Health ···············································································································
2. Forensic Medicine, and Medical Informatics and Economics ·····························································
Department of Forensic Medicine ·······································································································
Department of Medical Informatics and Economics ···········································································

Internal Medicine
1. Medicine Ⅰ ········································································································································
Department of Cardiovascular Medicine ·····························································································
Department of Respiratory Medicine ··································································································
Department of Gastroenterology ·········································································································

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2. Medicine Ⅱ ········································································································································
Department of Nephrology and Endocrinology ···················································································
Department of Metabolic Disease ········································································································
Department of Hematology and Oncology ··························································································
Department of Allergy and Rheumatology ··························································································
Department of Infectious Diseases ······································································································
Department of Stress Science and Psychosomatic Medicine ·······························································
3. Clinical Laboratory Medicine and Pathology ······················································································
Department of Clinical Laboratory Medicine （See Clinical Laboratory Center）
Department of Transfusion Medicine ··································································································
Reproductive, Developmental and Aging Sciences
1. Obstetrics and Gynecology ··················································································································
Department of Reproductive Endocrinology ·······················································································
Department of Gynecologic Oncology ································································································
Department of Perinatal Medicine ·······································································································
2. Pediatric Sciences
Department of Pediatrics, Department of Developmental Pediatrics ··················································
Department of Pediatric Surgery ·········································································································
3. Aging Sciences ····································································································································
Department of Geriatric Medicine, Department of Aging Research ···················································
Surgical Sciences
1. Surgery ·················································································································································
Department of Thoracic Surgery ··········································································································
Department of Cardiothoracic Surgery ································································································
Department of Gastrointestinal Surgery ·······························································································
Department of Hepatobiliary Pancreatic Surgery and Department of Artificial
Organ and Transplantation Surgery ······································································································
Department of Urology ························································································································
Department of Surgical Oncology ·······································································································
Department of Vascular Surgrry ···········································································································
Department of Metabolic Care and Endocrine Surgery ·······································································
2. Sensory and Motor System Medicine ··································································································
Department of Dermatology ················································································································

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Department of Plastic and Reconstructive Surgery ··············································································
Department of Oral-Maxillofacial Surgery ··························································································
Department of Orthopaedic Surgery ····································································································
Department of Ophthalmology ············································································································
Department of Otorhinolaryngology and Head & Neck Surgery ·························································
Department of Rehabilitation Medicine ·······························································································
3. Vital Care Medicine ·····························································································································
Department of Anesthesiology ·············································································································
Department of Clinical Emergency and Critical Care Medicine ·························································
Health Sciences and Nursing
1. Health Sciences ····································································································································
Department of Health Sociology ··········································································································
Department of Mental Health ··············································································································
Department of Biostatistics ··················································································································
Department of Social Gerontology ······································································································
Department of Biomedical Ethics & Department of Health Promotion Sciences ·································
2. Preventive and Administrative Nursing ·······························································································
Department of Nursing Administration/ Advanced Clinical Nursing ··················································
Department of Family Nursing ············································································································
Department of Community Health Nursing / Public Health Nursing ··················································
3. Clinical Nursing·································································································································

Department of Adult Nursing / Palliative Care Nursing ······································································
Department of Midwifery and Womenʼs Health ···············································································
Department of Psychiatric Nursing ······································································································
Department of Gerontological Nursing / Wound Care Management ···················································
International Health
1. International Social Medicine ··············································································································
Department of Health Policy and Planning ··························································································
Department of International Community Health ·················································································
2. International Biomedical Sciences ·······································································································
Department of Human Genetics ···········································································································
Department of Developmental Medical Sciences ················································································
Department of Human Ecology ···········································································································

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Department of Biomedical Chemistry ·································································································
University Hospital
Clinical Divisions ······································································································································
Cardiovascular Medicine (See Department of Cardiovascular Medicine)
Respiratory Medicine (See Department of Respiratory Medicine)
Gastroenterology (See Department of Gastroenterology)
Nephrology and Endocrinology(See Department of Nephrology and Endocrinology)
Metabolic Diseases (See Department of Metabolic Diseases)
Hematology and Oncology (See Department of Hematology and Oncology)
Allergy and Rheumatology (See Department of Allergy and Rheumatology)
Infectious Diseases (See Department of
Neurology (See Department of Infectious Diseases)
Geriatric Medicine(See Department of Geriatric Medicine, Department of Aging Research)
Psychosomatic Medicine(See Department of Stress Science and Psychosomatic Medicine)
General Surgery ···································································································································
Stomach and Eophagus Surgery (See Department of Gastrointestinal Surgery)
Colon and Rectal Surgery (See Department of Surgical Oncology)
Hepatobiliary Pancreatic Surgery(See Department of Hepatobiliary Pancreatic Surgery)
Vascular Surgery (See Department of Vascular Surgery)
Breast and Endocrine Surgery(See Department of Metabolic Care and Endocrine Surgery)
Artificial Organ and Transplantation Surgery(See Department of Artificial Organ and Transplantation Surgery)
Cardiovascular Surgery (See Department of Cardiothoracic Surgery)
Thoracic Surgery (See Department of Thoracic Surgery)
Neurosurgery (See Department of Neurosurgery)
Anesthesiology and Pain Relief Center (See Department of Anesthesiology)
Urology and Andrology (See Department of Urology)
Gynecologic Surgery (See Department of Obstetrics and Gynecology)
Dermatology and Photolaser Medicine (See Department of Dermatology)
Ophthalmology and Vision Collection (See Department of Ophthalmology)
Orthopaedic Surgery and Spinal Surgery(See Department of Orthopaedic Surgery)vi

Otorhinolaryngology, and Auditory and Voices Surgery(See Department of Otorhinolaryngology and Head & Neck Surgery)
Rehabilitation Medicine (See Department of Rehabilitation Medicine)
Plastic, Reconstructive and Aesthetic Surgery(See Department of Plastic and Reconstructive Surgery)
Oral-Maxillofacial Surgery Dentistry and Orhtodontics(See Department of Oral-Maxillofacial Surgery)
Pediatrics(See Department of Pediatrics, Department of Developmental Pediatrics)
Pediatrics Surgery (See Department of Pediatrics Surgery)
Obstetrics and Gynecology(See Department of Department of Reproductive Endocrinology / Department of ynecologic Oncology/ Department of Perinatal Medicine)
Neuropsychiatry (See Department of Neuropsychiatry)Radiology (See Department of Radiology)
Central Clinical Facilities ··························································································································
Clinical Laboratory Center (See Department of Clinical Laboratory Medicine)
Surgical Center ·····································································································································
Department of Clinical Radiology ·······································································································
Department of Emergency Services(See Department of Clinical Emergency and Critical Care Medicine)
Department of Transfusion Medicine and Immunohematology(See Department of Transfusion Medicine and Immunohematology)
Delivery Unit ·······································································································································
Central Rehabilitation Service ·············································································································
Department of Intensive Care Unit
(See Department of Clinical Emergency and Critical Care Medicine)
Division of Diagnostic Pathology ········································································································
Department of Corneal Transplantation ·······························································································
Department of Planning, Information, and Management(See Department of Medical Informatics and Economics)
University Hospital Medical Information Network (UMIN) Center ···················································
Organ Transplantation Service ·············································································································
Department of Cell Therapy and Transplantation Medicine ································································
Department of Infection Control and Prevention(See Department of Infection Control and Prevention)
Department of Endoscopy and Endoscopic Surgery ············································································
Department of Hemodialysis & Apheresis ···························································································

vii

Clinical Research Center ······················································································································
Division of Tissue Engineering ············································································································
Hospital Planning and Management ····································································································
Department of Child Physiology ··········································································································
Clinical Geonomics ······························································································································
Cooperative Unit of Medicine and Engineering Research ···································································
Pharmaceutical Service································································································································
Department of Pharmacy ·····················································································································
Center for Disease Biology and Integrative Medicine ···············································································
Division of Basic Medical Sciences (Ⅰ) ·····························································································
Division of Basic Medical Sciences (Ⅱ) ·····························································································
Division of Biomedical Materials and Systems ···················································································
Division of Clinical Biotechnology ·····································································································
Division of Environmental Health Sciences ························································································
Section of Animal Research, Division of Research Resources and Support ········································
Section of Radiation Biology ···············································································································
Section of Bioinformatics ····················································································································
Office of International Academic Affairs ···································································································The International Center for Research in Medical Education (ICRME) ···················································

viii

The Tokyo Journal of Medical Sciences. Vol. 115, October 2007

Teaching, Research, Secretarial
andAdministrative Staffs
Chief Members of Administration
Dean, Graduate School of Medicine

Nobutaka Hirokawa(Dean, Faculty of Medicine)
Chairman, School of Health Sciences and Nursing

Ichiro Kai

Director, Medical Library

Yasuyoshi Ouchi

Director General, University Hospital

Ryozo Nagai

Director, Center for Disease Biology and Integrative Medicine

Takao Shimizu

The director of the International Research Center for

Kimitaka Kaga

Medical Education.

Graduate School of Medicine
Molecular Cell Biology
Department of Cell Biology and Anatomy

professor

Nobutaka Hirokawa

Department of Biochemistry and Molecular Biology

professor

Hiroto Okayama

professor

Takao Shimizu

professor

Hiroki Kurihara

professor

Yasushi Miyashita

professor

Kensaku Mori

professor

Tomoyuki Takahashi

professor

Masamitsu Iino

professor

Masayoshi Mishina

professor

Masashi Fukayama

professor

Kohei Miyazono

professor

Akio Nomoto

professor

Kazuhiko Koike

professor

Tadatsugu Taniguchi

Department of Radiology

professor

Kuni Otomo

Department of Biomedical Engineering

professor

Joji Andoprofessor

Yasuo Ihara

professor

Nobumasa Kato

Functional Biology
Department of Physiology

Department of Pharmacology

Pathology, Immunology and Microbiology
Department of Pathology

Department of Microbiology

Department of Immunology
Radiology and Biomedical Engineering

Neuroscience
Department of Basic Neuroscience
Department of Speech and Cognitive Sciences
Department of Clinical Neuroscience

The Tokyo Journal of Medical Sciences. Vol. 115, October 2007ix

professor

Shoji Tsuji

professor

Nobuhito Saito

Department of Occupational, Environmental and Preventive

professor

Koji Matsushima

Medicine

professor

Yasuki Kobayashi

Department of Forensic Medicine, and Medical Informatics

professor

Kenichi Yoshida

and Economics

professor

Kazuhiko Ohe

professor

Ryozo Nagai

professor

Takahide Nagase

professor

Masao Omata

professor

Toshiro Fujita

professor

Takashi Kadowaki

professor

Mineo Kurokawa

professor

Kazuhiko Yamamoto

professor

Kazuhiko Koike

professor

Akira Akabayashi

professor

Yutaka Yatomi

professor

Koki Takahashi

professor

Yuji Taketani

professor

Osamu Tsutsumi

professor

Takashi Igarashi

professor

Tadashi Iwanaka

professor

Yasuyoshi Ouchi

professor

Shinichi Takamoto

professor

Michio Kaminishi

professor

Masatoshi Makuuchi

professor

Tadaichi Kitamura

professor

Hirokazu Nagawa

professor

Kunihiko Tamaki

professor

Isao Koshima

professor

Tsuyoshi Takato

professor

Kozo Nakamura

professor

Makoto Araie

professor

Kimitaka Kaga

professor

Nobuhiko Haga

Professor

Yoshitsugu Yamada

Social Medicine

Internal Medicine
Department of Medicine I

Department of Medicine II

Department of Clinical Laboratory Medicine and Pathology

Reproductive, Developmental and Aging Science
Department of Obstetrics and Gynecology

Department of Pediatric Science

Department of Aging Science
Surgical Sciences
Department of Surgery

Department of Sensory and Motor System Medicine

Department of Vital Care Medicine

The Tokyo Journal of Medical Sciences. Vol. 115, October 2007x

professor

Naoki Yahagi

professor

Norito Kawakami

professor

Yasuo Ohashi

professor

Ichiro Kai

professor

Akira Akabayashi

professor

Katsuya Kanda

professor

Sachiyo Murashima

professor

Keiko Kazuma

professor

Norito Kawakami

professor

Hiromi Sanada

Department of International Social Medicine

professor

Masamine Jinba

Department of International Biomedical Sciences

professor

Katsushi Tokunaga

professor

Hiroshi Ushijima

professor

Chiho Watanabe

professor

Kiyoshi Kita

Molecular Biomedicine for pathogenesis

professor

Toru Miyazaki

Division of Basic Medicine Sciences (2) Biophysics

professor

Haruo Kasai

Division of Biomedical Materials and Systems

professor

Takashi Ushida

Division of Clinical Biotechnology

professor

Kazunori Kataoka

Division of Environmental Biotechnology

professor

Chiharu tohyama

professor

Akio Nomoto

Health Sciences and Nursing
Department of Health Sciences

Department of Preventive and Administrative Nursing

Department of Clinical Nursing

International HealthCenter for Disease Biology and Integrative Medicine
Division of Basic Medicine Sciences (Ⅰ)

Division of Research Resources and Support
Section of Animal Research
Section of Radiation Biology

Kiyoshi Miyakawa

Section of Bioinformatics
International Academic Affairs

professor

Kazuhiko Yamamoto

Associate professor

Kiyoshi Kubota

Associate professor

Tetsuro Okabe

Associate professor

Satoru Yamagami

Faculty of Medicine
Endowed Departments
Department of Pharmacoepidemiology
Department of Integrated Traditional Medicine(Tsumura)

Department of Corneal Tissue Regeneration (Amniotec Inc.)

Department of Clinical Vascular Regeneration (Daiichi Pharmaceutical Co.)
Associate professor

Hiroyuki Koyama

The Tokyo Journal of Medical Sciences. Vol. 115, October 2007

xi

Department of Bone & Cartilage Regenerative Medicine
Department of “Menicon” Cartilage of Bone Regeneration
Associate professor

Kazuto Hoshi

Associate professor

Keiichi Hishikawa

professor

Hiroshi Suzuki

Department of Metabolome Professor Ryo Taguchi

Associate professor

Yoshiya Oda

Hospital Logistics by Sagawa Express Co.,Ltd.

professor

Hirohito Kuse

Associate professor

Takanari Gotoba

Associate professor

Kazuhiro Kakimi

Associate professor

Shinya Oku

Associate professor

Toshimasa Yamauti

Associate professor

Toshiaki Nakajima

professor

Koji Kawakami

Associate professor

Masataka Sata

Associate professor

Takashi Ebisawa

Associate professor

Dobun Hayashi

Department of Joint Disease Research

Associate professor

Noriko Yoshimura

Health Care Management and Policy

professor

Hideki Hashimoto

Associate professor

Naoto Hayashi

Associate professor

Kansei Uno

Hospital Environment

Associate professor

Yushi Uetera

Clinical Motor System Medicine

Associate professor

Akihiko Mabuchi

Clinical Drug Evalutaion

Associate professor

Fumihiko Kanai

Professor

Yasushi Kodama

Associate professor

Shoichi Maeda

Molecular Cardiovascular Metabolism

Associate professor

Katsuyuki AndoThe Department of Healthcare Quality Assessment

Associate professor

Noboru Motomura

Coca-Cola Anti-Aging Medicine

professor

Satoshi Inoue

Integrated Imaging Informatics

Associate professor

Naoki Yoshioka

Associate professor

Hoshio Uehara,

Department of Clinical Renal Regeneration
Department of Developmental and Medical Technology (Sankyo)

Clinical Molecular Epidemiology (Tanabe Seiyaku Co., Ltd.)

Immunotherapeutics (Medinet)
Healthcare Related Informatics (NTT DATA CORPORATION)

Division of Total Renal Care Medicine Associate
Integrated Molecular Science on Metabolic Diseases

Department of Advanced Clinical Science and Therapeutics
Sato Sports Plaza Co., Ltd Kaatsu Training

Department of Sleep Disorder Research (Alfresa)
Translational Research Based on the Clinical Database

Computational Diagnostic Radiology and Preventive Medicine

Medical Safety Management (Tokio Marine & Nichido)

Helth Service Center

The Tokyo Journal of Medical Sciences. Vol. 115, October 2007

xii

Tsukasa Sasaki,
Yasushi Okubo
International Research Center for Medical Education

Director

Kimitaka Kaga

professor

Kiyoshi Kitamura

Associate professor

Yuko Takeda

General Medicine

Head

Yasuyoshi Ouchi

Cardiovascular Medicine

Head

Ryozo Nagai

Respiratory Medicine

Head

Takahide Nagase

Gastroenterology

Head

Masao Omata

Nephrology and Endocrinology

HeadToshiro Fujita

Metabolic Diseases

Head

Takashi Kadowaki

Hematology and Oncology

Head

Mineo Kurokawa

Allergy and Rheumatology

Head

Kazuhiko Yamamoto

Infectious Diseases

Head

Kazuhiko Koike

Neurology

Head

Shoji Tsuji

Geriatric Medicine

Head

Yasuyosi Ouchi

Psychosomatic Medicine

Head

Akira Akabayashi

General Surgery

Head

Masatoshi Makuuchi

Stomach and Esophagus Surgery

HeadMichio KaminishiColon and Rectal Surgery

Head

Hirokazu Nagawa

Hepatobiliary Pancreatic Surgery

Head

Masatoshi Makuuchi

Vascular Surgery

Head

Hirokazu Nagawa

Breast and Endocrine Surgery

HeadMichio Kaminishi

Artificial organ and Transplantation Surgery

Head

Masatoshi Makuuchi

Cardiovascular Surgery

HeadShinichi Takamoto

Thoracic Surgery

HeadShinichi Takamoto

Head

Nobuhito Saito

Anesthesiology and Pain Relief Center

Head

Yoshitsugu Yamada

Urology and Andrology

Head

Tadaichi Kitamura

Gynecologic Surgery

HeadOsamu Tsutsumi

Dermatology and Photolaser Medicine

Head

Kunihiko Tamaki

Ophthalmology and Vision Collection

Head

Makoto Araie

Orthopaedic and Spinal Surgery

Head

Kouzo Nakamura

Otorhinolaryngology and Auditory and Voice Surgery

Head

Kimitaka Kaga

Head

Kouzo Nakamura

Plastic, Reconstructive and Aesthetic Surgery

Head

Isao Koshima

Oral-Maxillofacial Surgery, Dentistry and Orthodontics

Head

Tsuyoshi Takato

University Hospital
Clinical Divisions

Neurosurgery

Rehabilitation Medicine

The Tokyo Journal of Medical Sciences. Vol. 115, October 2007

xiii

Pediatrics

Head

Takashi Igarashi

Pediatric Surgery

Head

Tadashi Iwanaka

Obstetrics and Gynecology

Head

Yuji Taketani

Neuropsychiatry

Head

Nobumasa KatoRadiology

Head

Kuni Ohtomo

Clinical Laboratory Center

Head

Yutaka Yatomi

Surgical Center

Head

Hiroshi YasuharaRadiological Center

Head

Kuni Ohtomo

Emergency Services

Head

Naoki Yahagi

Transfusion Medicine and Immunohematology

HeadKoki Takahashi

Department of Maternal, Fetal, and Neonatal Medicine

Head

Yuji Taketani

Rehabilitation Service

Head

Kouzo Nakamura

Department of Medical Engineering

Head

Hisayoshi Tamai

Central Supply Service

Head

Yoshikazu Mimura

Intensive Care Unit

Head

Naoki Yahagi

Intensive Pathology

Head

Masashi Fukayama

Corneal Transplantation

Head

Shiro Amano

Department of Cell Therapy and Transplantation Medicine

Head

Shigeru Chiba

Department of Endoscopy and Endoscopic Surgery

Head

Takao Kawabe

Center for Hemodialysis and Apheresis

Head

Toshiro Fujita

Department of Medical Social Service and Welfare

Head

Yasuyoshi Ouchi

Clinical Research Center(tentative name)Head

Masao Omata

Infection Control and Prevention

Head

Kazuhiko Koike

Department of Planning, Information and Management

Head

Kazuhiko Ohe

University Hospital Medical Information Network Center

Head

Takahiro Kiuchi

Department of Organ Transplantation Service

Head

Masatoshi Makuuchi

Division of Tissue Engineering

Head

Tsuyoshi Takato

Department of Clinical and Genetic Informatics

Head

Ryozo Nagai

Department of Palliative Medicine

Head

Keiichi Nakagawa

Pharmaceutical Department

Head

Hiroshi Suzuki

Department of Child Psychiatry

Head

Nobumasa Kato

Central Clinical Facilites

xiv

The Tokyo Journal of Medical Sciences. Vol. 115, October 2007

Organization Chart
Cell Biology
Cell Biology and Anatomy

Structural Biology
Structural Cell Biology

Molecular Cell Biology

Cellular Neurobiology
Molecular Biology
Biochemistry and Molecular Biology

Cellular Signaling
Physiological Chemistry andMetabolism
Integrative Physiology

Physiology
Functional Biology

Cellular and Molecular Physiology
Neurophysiology

Pharmacology

Cellular and Molecular Pharmacology
Molecular Neurobiology
Human Pathology and Diagnostic Pathology

Pathology

Molecular Pathology
Surgical Pathology

Pathology, Immunology
and Microbiology

Microbiology

Microbiology
Infection Control and Prevention

Immunology

Molecular Immunology
Clinical Immunology
Diagnoatic Radiology

Radiology

Radiotherapy
Nuclear Medicine

Radiology and Biomedical
Engineering

Radiation Oncology/Experimental
Radiology
System Physiology
Bioimaging and Biomagnetics
Biomedical Engineering

Biosystem Construction and Control
Biomechanics
Medical Optics
Clinical Engineering
Neuropathology

Basic Neuroscience
Graduate School of
Medicine

Neurochemistry
Neurobiology
Speech Science

Neuroscience

Speech and Cognitive Neuroscienes

Cognitive Neuroscience
Speech Physiology
Sensory and Motor Neuroscience
Neuropsychiatry

Clinical Neuroscience

Neurology
Neurosurgery
Molecular Preventive Medicine

Social Medicine

Occupational, Environmental andPreventive Medicine

Public HealthRadiological Health

The Tokyo Journal of Medical Sciences. Vol. 115, October 2007

Forensic Medicine, and Medical
Informatics and Economics

Forensic Medicine
Medical Informatics and Economics
Cardiovascular Medicine
Vascular Biology

Medicine I

Respiratory Medicine
Gastroenterology
Nephrology
Endocrinology

Internal Medicine

Nutrition and Metabolism
Medicine II

Hematology and Oncology
Allergy and Rheumatology
Infectious Diseases
Stress Science and Psychosomatic
Medicine
Clinical Laboratory Medicine

Clinical Laboratory Medicine
and Pathology

Diagnostic Pathology
Transfusion Medicine
Reproductive Endocrinology

Obstetrics and Gynecology

Gynecological Oncology
Perinatal Medicine
Molecular Reproductive Medicine
Pediatrics

Reproductive,
Developmental andAging Sciences

Pediatric Sciences

Developmental Pediatrics
Pediatric Surgery
Pediatric Oncology

Aging Sciences

Geriatrics
Aging ResearchThoracic Surgery
Cardiovascular Surgery
Gastrointestinal Surgery
Hepato Biliary Pancreatic Surgery

Surgery

Urology
Artificial Organ and Transplantation
Division
Surgical Oncology

Surgical Sciences

Vascular Surgery
Metabolic Care and Endocrine
Surgery
Dermatology
Plastic and Reconstructive Surgery
Oral and Maxillofacial Surgery
Sensory and Motor System
Medicine

Orthopaedic Surgery
Ophthalmology
Otorhinolaryngology and Head & Neck
Surgery
Rehabilitation Medicine

Vital Care Medicine

Anesthesiology
Emergency and Critical Care Medicine

xv

The Tokyo Journal of Medical Sciences. Vol. 115, October 2007

xvi

Health Sociology
Mental Health
Epidemiology and Preventive Health
Sciences
Health Sciences

Social Gerontology
Health Promotion Sciences
Biostatistics
Biomedical Ethics

Health Sciences andNursing

Advanced Clinical Nursing
Nursing Administration
Preventive and Administrative
Nursing

Family Nursing
Community Health Nursing
Public Health Nursing
Adult Nursing
Palliative Care Nursing

Clinical Nursing

Midwifery and Woman’s Health
Psychiatric Nursing
Gerontological Nursing
Wound Care Management

International Social Medicine

Health Policy and Planning
International Community HealthInternational Health

Human Genetics
International Biomedical
Sciences

Developmental Medical Sciences
Human Ecology
Biomedical ChemistryCenter for Disease Biology
and Integrative medicine

Division of Basic Medical Sciences (Ⅰ)
Division of Basic Medical Sciences (Ⅱ)
Division of Biomedical Materials and Systems
Division of Clinical Biotechnology
Division of Environmental Health Sciences
Division of Research Resources and Support

Faculty of Medicine
Graduate School of Medicine
Administrative Division

Administrative OfficeSection of Animal Research
Section of Radiation Biology
Section of Bioinformatics

Cell Biology and Anatomy
Biochemistry and Molecular Biology
Physiology
Pharmacology
Pathology
Microbiology
Immunology
Radiology
Biomedical Engineering
Basic Neuroscience
Speech and Cognitive Sciences
Clinical Neuroscience
School of Medicine

Occupational, Environmental and Preventive Medicine
Medical Principles and Medical Ethics

The Tokyo Journal of Medical Sciences. Vol. 115, October 2007
Forensic Medicine, and Medical Informatics and Economics
Medicine I
Medicine II
Clinical Laboratory Medicine and Pathology
Obstetrics and Gynecology
Pediatric Science
Aging Science
Surgery
Sensory and Motor System Medicine
Vital Care Medicine
Family Nursing
School of Health Sciences
and Nursing

Comunity Health Nursing
Fundamental Nursing
Adult Health and Nursing
Mental Health and Nursing
Health Sociology
Health Administration
Epidemiology and Biostatistics
Human Ecology
Biochemistry and Nutrition
Maternal and Child HealthFaculty of
Medicine

Endowed Department

Pharmacoepidemiology
Integrated Traditional Medicine (Tsumura)
Corneal Tissue Regeneration (Amniotec inc.)
Clinical Vascular Regeneration (Daiichi Pharmaceutical Co.)
Bone & Cartilage Regenerative Medicine
Hematopoietic Regeneration“Menicon”Caartilage of Bone Regeneration
Clinical Renal Regeneration
Developmental nd Medical Technology(Sankyo)
Metabolome
Systematic Clinical Oncology
Hospital Logistics by Sagawa Express Co. Ltd.
Clinical Molecular Epidemiology (Tanabe Seiyaku Co. Ltd.)
Immunotherapeutics (Medinet)
Healthcare Related Informatics (NTT DATA CORPORATION)
Total Renal Care Medicine
Integrated Molecular Science on Metabolic Diseases
Advanced Clinical Science and Therapeutics
Sato Sports Plaza Co.Ltd. Kaatsu Training
Sleep Disorder Research (Alfresa)
Translational Research Based on the Clinical Database
Joint Disease Research
Health Care Management and Policy
Computational Diagnostic Radiology and Preventive Medicine

xvii

The Tokyo Journal of Medical Sciences. Vol. 115, October 2007

xviii

General Medicine
Cardiovascular Medicine
Respiratory Medicine
Gastroenterology
Nephrology and Endocrinology
Internal Medicine

Metabolic Diseases
Hematology and Oncology
Allergy and Rheumatology
Infectious Diseases
Neurology

ClinicalDivisions

Geriatric Medicine
Psychosomatic Medicine
General Surgery
Stomach and Esophageal Surgery

Universit
Hospital

Colon and Rectal Surgery
Hepato Biliary and Pancreatic Surgery
Vascular Surgery
Breast and Endocrine Surgery
Surgery

Artificial organ and Transplantation Surgery
Cardiovascular Surgery
Thoracic Surgery
Neurosurgery
Anesthesiology and Pain Relief Cente
Urology and Andrology
Gynecologic Surgery
Dermatology and Photolaser Medicine
Ophthalmology and Vision Collection
Orthopaedic Surgery and Spinal Surgery

Sensory and Motor System
Medicine

Otorhinolaryngology, and Auditory and Voice Surgery
Rehabilitation Medicine
Plastic, Reconstructive, and Aesthetic Surgery
Oral-Maxillofacial Surgery, Dentistry andOrthodontics
Pediatrics

Pediatrics, Perinatal and
Women's Medicine

Pediatric Surgery
Obstetrics and Gynecology

Neuropsychiatry

NeuropsychiatryRadiology

Radiology
Clinical Laboratory Center
Surgical Center
Radiological Center
Emergency Services
Transfusion Medicine
Delivery Unit

Central Clinical Facilities

Rehabilitation Service
Medial Engineering Supply Center

The Tokyo Journal of Medical Sciences. Vol. 115, October 2007

xix

Intensive Care Unit
Pathology
Sectin of Corneal Transplantation
Department of Cell and Gene Therapy
Department of Endoscopy and Endoscopic Surgery
Department of Hemodialysis and Apheresis
Hospital Computer Center
Department of Medical Social Service and Welfare
Clinical Research Center
Infection Control and Prevention
University Hospital Hospital Medical Information
Network Center
Organ Transplantation Service
Department of Nutrition
Labor Safety and Health Management Office
Project Team For Hospital Development
Department of Clinical and Genetic Informatics
The Clinical Training Center
Department of Palliative Medicine
Public Relations Office
Department of Clinical Genomics
Cooperative Unit of Medicine and Engineering Research
Pharmaceutical Department
Nursing Department
Administration Office

The Tokyo Journal of Medical Sciences. Vol. 115, October 2007

xx

History1858

May.

82 practitioners trained in Dutch (European) medicine in Edo (Tokyo) laid out money andestablished at Kanda Mitamagaike Vaccination station called the Shutojyo (vaccination center).

Nov.

The Shutojyo burned by a fire which emerged from Kanda Aioicho, continued its operationat
othersites such as a residence of Ito Genboku.

1859

Sep.

The Shutojyo was moved to and reconstructed at Shitaya Izumibashi Dohri.

1860

Oct.

TheShutojyo became an official medical institution of the Shogunate Government.

1861

Oct.

The Shutojyo was renamed as Seiyo Igaku-syo (Institute of Western Medicine) and offeredcourses ofWestern medicine in the fields of education, autopsy, and vaccination.

1863

Feb.

The Seiyo Igaku-sho was renamed as Igaku-sho (Institute of Medicine).

1868

Jul.

The Igaku-sho, affiliated with the Military hospital which was moved from Yokohama to Todo
residence in Shitaya, was renamed as Daibyoin (the Great Hospital).

1869

1871

Feb.

The Daibyoin renamed as Igakko-ken-byoin (Medical School and Hospital).

Dec.

Igakko-ken-byoin was renamed as Daigaku-Higashiko (University East Building).

Jul.

Ministry of Education was established and Daigaku-Higashiko was renamed as Higashiko(EastBuilding).

1872

Aug.

SchoolSystemwasestablished,renaming

HigashikoasDaiichi-daigaku-ku-igakko(The1stUniversity District Medical School).
1874

May.

Daiichi-daigaku-ku-igakko was renamed as Tokyo-igakko (Tokyo Medical School).

1876

Nov.

Tokyo-Igakko was moved to Hongo.

1877

Apr.

Tokyo-Igakko, affiliated with Tokyo-Kaisei School, renamed as The University of Tokyo.Tokyo
Medical School was renamed as The University of Tokyo Faculty of Medicine.

1886

Mar.

The University of Tokyo was renamed as Imperial University, and University of Tokyo FacultyofMedicine renamed as Imperial University Medical college. Graduate School was established.

1897

Jun.

The Imperial University was renamed as Tokyo Imperial University.

1917

Aug.

Eiraku Hospital affiliated with Ministry of Education Medical Practice License Examination,
moved to Tokyo Imperial University and renamed as Koishikawa hospital affiliated to Tokyo
Imperial University Medical College.

1919

Apr.

Faculty system was established renaming Medical College as Faculty of Medicine.

1931

Feb.

The first building of the Faculty of Medicine was constructed.

1936

Jan.

Brain research office donated by Mr. Horikoshi Hisasaburo.

Nov.

The second building of the Faculty of Medicine (main building) was constructed.

1947

Oct.

Tokyo Imperial University renamed as The University of Tokyo.

1950

Apr.

Institute of Nursing renamed as University Nursing School.

1953

Apr.

School of Health Care and Nursing founded.

Jul.

Graduate School of the new system founded, Division of Biological Science Dr. Med.of
Medicine.

1956

Apr.

Midwives School established.

The Tokyo Journal of Medical Sciences. Vol. 115, October 2007

1958

1961

1965

Apr.

Division of Pharmaceutical Sciences became independent Faculty.

May.

Celebrated centennial of The University of Tokyo Faculty of Medicine.

Mar.

Medical Library was built in memorial of the centenary.

Apr.

Institute of Medical Electronics established.

Apr.

Research Institute of Logopedics and Poniatrics was established.

xxi

School of Health Care and Nursing reorganized as the School of Health Sciences.
Graduate School of The University of Tokyo Reorganized and Division of Biological Science.
Dr.Med. Science course became Medical Science Division.
Health Science Course was established in Medical Science Division.
1966

Sep.

The third building of Faculty of Medicine was constructed.

1971

Apr.

Laboratory for Animal Experiments was established.

1973

Mar.

Animal Center for Biomedical Research was constructed.

1983

Jan.

Annex of the third building of the Faculty of Medicine was constructed.

1985

Sep.

Medical and International Academic Affairs established.

1987

Apr.

Graduate School specialized course was changed to major.

1992

Apr.

School of Health Sciences became The School of Health Science and Nursing.
School of International Health was established in Medical Science Division.

1995

Jul.

Radiation Research Institute was established.

Apr.

As the result of the shift to the chair system of the Graduate School of Medicine, four divisions
were abolished, Third Basic Medicine, Social Medicine, Third Clinical Medicine and Fourth
Clinical Medicine. Instead, four divisions were established, Pathology, Immunology andMicrobiology, Social Medicine, Reproductive, Developmental and Aging Science and Surgery.

1996

Apr.

As the result of the shift to the chair system of the Graduate School of Medicine, three divisions
were abolished, First Clinical Medicine, Health Science and International Health. Instead, threedivisions were established, Internal Medicine, Health Science and Nursing and International
Health.

1997

Apr.

As the result of the shift to the chair system of the Graduate School of Medicine, three divisions
were abolished, First Basic Medicine, Second Basic Medicine and Second Clinical Medicine.
Instead four divisions were established. Molecular Cell Biology, Functional Biology, Radiology
and Biomedical Engineering and Neuroscience.
As the result of above mentioned reorganization, three institutes were abolished, Institute ofBrain Research, Institute of Medical Electronics and Institute of Logopedics and Phoniatrics.

1999

Apr.

Master Course of Medical Science was established in Graduate School of Medicine.
This course accepts graduates of all faculties except those from Schools of Medicine, Dentistry,and Veterinary Medicine.

2000

Apr.

The International Research Center for Medical Education was established.
(The shared facility for education and research)

2001

Apr.

University Branch Hospital was united to University Hospital.

2003

Apr.

The Center for Disease Biology and Integrative Medicine was established.

2

Department of Cell Biology andAnatomyProfessor
Nobutaka Hirokawa, M.D.

Associate Professor
Yoshimitsu Kanai, M. D., Takao Nakata, M. D.,

Yosuke Takei, M. D.,

Sen Takeda, M. D.

Lecturer
Yasuko Noda, M. D.,

Associate
Yasushi Okada, M. D.,
Ryo Nitta, M. D.,
Hiroaki Yajima, Ph. D.

Homepage

Yosuke Tanaka, M. D., Masahiko Kawagishi, M. D.,
Noriko Homma, Ph. D., Harukata Miki, Ph. D.,
Tadayuki Ogawa

http://cb.m.u-tokyo.ac.jp/

Teaching activities
Our teaching responsibility is following.
I.
1) Lecture on Cell Bilogy, Histology and Neurocytology.
2) Lecture on Gross Anatomy and Neuroanatomy. to
medical students and students of other facultiesII.
1) Laboratory course of Gross Anatomy and Neuroanatomy.
2) Laboratory course of Histology and Histology of
the Cenrtral Nervous System.
to medical students and students of other faculties.
In addition we offer a special training course (freequarter) of various kinds of molecular cell biology
techniques such as immunocytochemistry, electron
microscopy, biochemistry, molecular biology, biophysics, and cellular and molecular neurobiology
technique to medical students.

Research activities
Our research field covers the molecular cell biologyof the cytoskeleton. We focus on the molecularmechanisms of cell morphogenesis and intracellulartransports.
Our laboratory studies molecular architecture, dynamics and function of the neuronal cytoskeleton using various new molecular cell biological approaches
including new electron microscopy such as the quick
freeze deep etch electron microscopy, cryoelectron
microscopy at atomic resolution, and cryoultramicrotomy, biochemistry, immunocytochemistry, molecularbiology, molecular genetics such as gene targeting andtransgenic mouse approaches, molecular biophysics
and structure biology including X ray crystallography
and cryoelectron microscopy.
In this way we can study structure, dynamics andfunctions of cytoskeleton from gene to cell, tissue andwhole body.
Nerve cells as units of complicated neuronal networks in the brain develop very polarized morphology

3composed of dendrites, cell body and a long axon
along the direction of impulse propagation. The neuronal cytoskeleton plays three major important roles.
1) It provides dynamic frameworks for neurite extension and maintenance.
2) It provides structural bases for organelle transports
in the cells. Namely it works as rails and motor molecules to transport materials from cell center to periphery and from periphery to cell center.
3) It very importantly regulates release processes oftransmitters and also contributes to anchor receptors at
the postsynaptic sites.
Our laboratory studies molecular architecture, dynamics and function of the cytoskeleton focusing onthese three major roles.
To study these molecular mechanisms we use newmolecular cell biological approaches including electron microscopy of molecular resolution, biochemistry,
biophysics, molecular biology and molecular genetics
and X-ray crystallography.

References
1. Hirokawa, N. and R. Takemura. Molecular motors
and mechanisms of directional transport in neurons. Nature Rev Neurosci 6: 201-214, 2005.
2. Teng J., T. Rai, Y. Tanaka, Y. Takei, T. Nakata, M.
Hirasawa, A. B. Kulkarni, and N. Hirokawa. The
KIF3 motor transports N-cadherin and organizes
the developing neuroepithelium. Nature Cell Biol
7: 474-482, 2005.
3. Tanaka, Y., Y. Okada, and N. Hirokawa. FGF-induced
vesicular release of Sonic hedgehog and retinoic
acid in leftward nodal flow is critical for left-rightdetermination. Nature 435: 172-177, 2005.
4. Okada, Y., S. Takeda, Y. Tanaka, J.-C. I. Belmonteand N. Hirokawa. Mechanism of nodal flow: aconserved symmetry breaking event in left-rightaxis determination. Cell 121: 633-644, 2005.
5. Miki. H., Y. Okada, and N. Hirokawa. Analysis of
the kinesin superfamily: insights into structureand function. Trend Cell Biol 15: 467-476, 2005.
6. Hirokawa, N., Y. Tanaka, Y. Okada and S. Takeda.
Nodal flow and the generation of left-rightasymmetry. (Review Article) Cell 125 (1): 33-45,
2006.
7. Midorikawa R., Y. Takei, and N. Hirokawa. KIF4

motor regulates activity-dependent neuronal survival by suppressing PARP-1 enzymatic activity.
Cell 125: 371-383, 2006.
8. Hirokawa, N. mRNA Transport in Dendrites:
RNA Granules, Motors, and Tracks. Journal of
Neuroscience 26: 7139-7142, 2006.
9. Kikkawa, M. and N, Hirokawa. High-resolution
cryo-EM maps show the nucleotide binding
pocket of KIF1A in open and closed conformations. EMBO Journal 25: 4187 - 4194, 2006.
10. Nakata, T and N. Hirokawa. Neuronal Polarity
and the Kinesin Superfamily Proteins. Science
STKE 6 February 2007: pe6

6

Department of Molecular Biology
Professor
Hiroto Okayama, M.D., Ph.D.

Associate Professor
Shigeki Jinno, Ph.D.

Associate
Hanako Yamamoto, Ph.D.,

Homepage

Kenji Ito, Ph.D.,

Shiho Arakawa, Ph.D.

http://www.cellcycle.m.u-tokyo.ac.jp/

Introduction and Organization
This Department was established in 1893 initially as
a part of Department of Physiology, but in 1897
became independent. In 1927, it was renamed
Department of Biochemistry, in 1974 First Departmentof Biochemistry and in 1997 Department of Molecular
Biology, according to the creation of new related
departments and the reorganization of Faculty of
Medicine. This Department has been headed by 7
professors, who made great contributions to thedevelopment of biochemistry, nutrition and molecularbiology in Japan.
Professor Muneo Kumagawa, who headed this first
Biochemistry or Medical Chemistry Department
established in this country, graduated in 1882 The
University of Tokyo Faculty of Medicine. In 1884 hewent to Department of Pathology, The University of
Berlin headed by Rudolf Virchow and under thesupervision of Ernst Salkowski. After returning toJapan, he was promoted to Lecture and Professor ofthis Department. In 1908, He discovered lack ofglycogenecity in lipids, which has been firmly
established besides some exceptions, and succeeded inpurification of vitamin B1, which was discovered by C.
Eijikman in 1906. He educated many including
Masahiro Sakaguchi, who developed a world-famouscolorimetric method for arginine and Takaoki Sasaki,
who first succeeded in generating liver cancer withchemicals.

Professor Samuro Kakiuchi graduated The Imperial
University of Tokyo Faculty of Medicine in 1906 andstudied under Professor Kumagawa. After studies in
US, he come back and succeeded late Kumagawa. He
published Journal of Biochemistry and founded theJapanese Society of Biochemistry. His students
included Professors Kodama and Shimazono.
Professor Keizo Kodama graduated the Imperial
University of Tokyo in 1918. Taking positions oflecturer and Associate Professor and making studies at
Cambridge University, he became Professor of
Biochemistry Kyushu Imperial University andsucceeded Professor Kodama in 1933. He studied
oxidation and reduction and nutrition.
Professor Norio Shimazono graduated The Imperial
University of Tokyo Faculty of Medicine in 1928,
followed by taking positions as associate, lecturer,
professor at Niigata Medical School. In 1952 hesucceeded Professor Kodama. He studied vitamin B1/
cocarboxylase, ketoacid metabolism and hexose
metabolism.
Professor Tamio Yamakawa graduated The Imperial
University of Tokyo Faculty of Medicine and began
studies at The Institute for Infectious Diseases, The
University of Tokyo. After becoming Associate
Professor and Professor, he succeeded Professor
Shimazono. He was a pioneer in glycolipid researchand discovered the involvement of sialic acid in the
ABO blood type antigens.
Professor Masami Muramatsu graduated The

7

University of Tokyo Faculty of Medicine in 1955. He
began studies in Department of Internal Medicine,went to Baylor Collage of Medicine to study under H.
Busch, and after coming back, took a position at
Cancer Institute and professorship at Tokushima
University School of Medicine. In 1982, he succeeded
Professor Yamakawa. He studied ribosomal RNA andcloned interferon and p450 genes.
Professor Hiroto Okayama graduated Kumamoto
University School of Medicine in 1973. After taking a
Ph.D. degree at Kyoto University School of Medicine,
he went to Stanford University to study under P. Berg.
Taking a position at NIH US, he became Professor of
Molecular Genetics, Osaka University Institute for
Infectious Diseases. In 1993 he succeeded Professor
Muramatsu. At Stanford and NIH, he studied genecloning and developed a full length cDNA cloning
method and a cDNA expression cloning vector system.
After return to Japan, he has been studying cell cycle
control and cancer.

Research Activities
Our current study focuses on the understanding of
the molecular mechanism enabling the anchorageindependent S phase onset, which is the universal
property of cancer cells. All the members of ourlaboratory are participating in this study.
1. Molecular Mechanism for anchorage lossinduced Cdc6 degradation.
In 2002, we reported that anchorage deprivation
led to termination of expression of Cdc6, a factor
essential for the assembly of Pre-RC, via
Rb-independent transcriptional repression andpapainfamilyprotease-led
degradation.
Subsequently, we identified the protease as
lysosomal cathepsins, released from lowcholesterol-content lysosomes upon anchorage
deprivation. Although cathepsins appear to be themajor Cdc6 degrading enzyme in NRK cells, they
are not major ones in other cells such as mouse or
rat embryonic fibroblasts. We recently found that
two ubiquitin ligases are responsible for anchorageloss-induced Cdc6 degradation, one of which is
identified as Cdh1-APC. Search for the otherubiquitin ligase is underway. We further found that
the Tsc2-Rheb-mTOR pathway is involved in thecontrol of Cdc6 degradation upon anchorage loss.
2. New function of Cdc6
Cdc6 is known as the assembler of
pre-replicative complexes that is the initial step ofchromosomal replication. We found that this factor
has an additional function: the ability to activate
p21WAF1-inhibited Cdk2 in a ATP-dependent
manner, the function never anticipated for Cdc6
and never anticipated for the regulation of acyclin-dependent kinase. This discovery highlights
the importance of Cdc6 as a focal point of thecontrol of S phase onset and progression.
3. Induction of anchorage-independent proliferation of NRK cells by overexpression of threecell cycle factors
One approach to understand the mechanism of
oncogenetic transformation is to find a way to
induce anchorage-independent proliferation ofcells by manipulating cell cycle factors. This could
be done with NRK cells and overexpression of
three factors: Cdc6, Cdk6 and cyclin D3, the latter
two of which can evade inhibition by inhibitor
proteins and activate E2F under growth
suppressive conditions like in anchorageloss-induced G1 arrest. This finding is being
confirmed with mouse embryonic fibroblasts andequivalents.

Education
To medical students, we give lectures on DNA andrelated. DNA replication, transcription, nuclear export
of mRNA, translation, gene engineering and mobile
DNA are the topics covered by the lectures.
To graduate course students, the genetic engineeringcourse consisting of lectures and experiments isprovided.

References
1. Horiuchi, K., Umetani, M., Minami, T., Okayama,
H., Takada, S., Yamamoto, M., Aburatani, H., Reid,
P. C., Housman, D. E., Hamakubo, T., and Kodama,
T. Wilms’ tumor 1-associating protein regulates
G2_M transition through stabilization of cyclin A2

8

mRNA. 2006, Proc. Natl. Acad. Sci. USA, 103,
17278-17283.
2. Isobe, H., Nakanishi, W., Tomita, N., Jinno, S.,
Okayama, H., and Nakamura, E. Gene delivery byaminofullerenes: Structure requirement for efficienttransfecion. 2006, Chemistry-an Asian Journal 1,
168-175.
3. Isobe, H., Nakanishi, W., Tomita, N., Jinno S.,
Okayama, H. and Nakamura, E. Nonviral genedelivery by aminofullerene. 2006, Mol Pharm 3,
124-134.

9Department of Cellular Signaling
Professor
Takao Shimizu, M,D., Ph.D.

Associate Professor
Motonao Nakamura, Ph.D.,

Satoshi Ishii, Ph.D.

Associate
Yoshihiro Kita, Ph.D.,

Homepage

Hideo Shindou, Ph.D.

http://biochem2.umin.jp/index.html

Introduction and Organization
In addition to the above 5 faculty members, we have
18 graduate students (16 doctor course students
including 2 PhD-MD course students and 2 mastercourse students), and 2 undergraduate medical
students (Free Quarter). Several clinical scientists anda research fellow from pharmaceutical company arealso our members. Ms Toshie Takahashi (Assistant)belongs to the Dean of the Faculty and is in charge of
maintenance and education of various instruments forcommon use.

Teaching activities
For about 100 undergraduate students from theFaculty of Medicine, and about 5 students fromFaculty of Science (Department of Anthropology), we
deliver about 80 lectures, small-group seminars, andlaboratory course for a couple of weeks. Ourlaboratory is accepting Free Quarter students every
year, and the total number from 2003 to 2006 isaround 10. For graduate course students, we havethree-month lecture series (biochemistry and genetic
engineering), and an eight-week laboratory course forclinical scientists.

Research activities
1. Lipid mediator cellular signaling.

Oxygenated products of arachidonic acid(prostaglandins, leukotrienes, and hydroxyeicosatetraenoic acids) as well as bioactive
phospholipids (platelet-activating factor and otherrelated phospholipids) activate cellular signaling
pathways in various cells. These lipid mediators,
working together with other bioactive substancessuch as neurotransmitters and cytokines, are now
considered to play significant roles in neuronalplasticity and self-defense systems. To identify theroles of lipid mediators in the living systems,
principally three approaches are ongoing withdifferent strategies; (1) isolation of enzymes
involved in syntheses and degradation of lipid
mediators, cloning of cDNAs and genes, elucidationof enzyme regulation at transcriptional andposttranscriptional levels. (2) cloning of G-proteincoupled receptors for lipid mediators andclarification of intracellular signaling mechanisms;
and (3) target disruption or overexpression of thegene of interest in mice, and identification of the invivo role of each molecule by examining
phenotypes of these mice. In the last several years
we have cloned several key enzymes ofphospholipid metabolism and receptors for lipid
mediators. Several lines of transgenic mice andknock-out mice were established and theirphenotypes were analyzed. We found that these
mediators are involved in inflammation, allergy, andneuronal functions.

10

2. Simultaneous quantitation of lipid mediators.
Lipid mediators are produced through a cascade
pathway. In the cascade known as “arachidonate
cascade”, several key enzymes such as cytosolic
phospholipase
A2,
cyclooxygenases,
andlipoxygenases function as common regulators incombination with various terminal synthases that
produce specific lipid mediator molecular species.
For a comprehensive analysis of lipid mediators, asimultaneous quantitation method with sensitivity
and reliability is necessary. Thus, we have recently
developed a quantitation system for multiplex lipid
mediators by column-switching HPLC–tandem
mass spectrometry. When optimized, the systemenables the rapid analysis of 14 lipid mediators witha throughput of 96 samples/24 h, lower limits ofquantitation of 5 pg on column, and linear
calibration ranges up to 2000–5000 pg. Indeed, we
successfully detected dynamic changes in a series oflipid mediators in some pathologic tissues ofrodents.
3. Various instrumental analyses.
The Faculty of Medicine has various analyticaland preparative instruments for the common use,which include mass spectrometers (JEOL HX 110,
Hitachi M-80 and Finnigan MAT TSQ 7000
[ThermoQuest]) equipped with gas chromatographs
or HPLC, PerkinElmer peptide sequencers, FUJI
BAS 2000 image analyzer, BD FACScan, andBeckman capillary electrophoresis system (P/ACE
2000). Ms. Takahashi is in charge of themaintenance of these machines and instruction forthe beginners. As her own projects, she isidentifying peptide sequences of various proteins by
HPLC-MS, and identification of small-molecularweight compounds by GC-MS and HPLC-MS.
4. Internet Web site
To see our research activities in more detail,please refer to our web site (http://biochem2.umin.
jp/index_j.html). In this homepage, you will alsofind our experimental protocol useful for themolecular and cellular biology studies. Dr. Kita is
responsible for the homepage.
5. Collaboration with Department of Metabolome

In 2003, a new laboratory, Department ofMetabolome was established by the donation of
Shimadzu Co., Ltd, and Ono Pharmaceutical Co.
Professor Ryo Taguchi and Associate Professor
Yoshiya Oda are worldwide leading researchers onproteomics and metabolomics. In collaboration withthem, we are searching for novel lipid mediatorsthat bind to orphan G-protein-coupled receptors,
lacking identified cognate ligands. Recently, we
succeeded in molecular cloning of lung-typeacyl-coa:lysophosphatidylcholine acyltransferase 1(LPCAT1) involving in production of lungsurfactant.

References
1. Ando K, Tsuji E, Ando Y, Kunitomo J, Kobayashi
R, Yokomizo T, et al. Synthesis of 2-, 4- and 5(2-alkylcarbamoyl-1methylvinyl)-7alkyloxybenzo[b]furans and their leukotriene B4
receptor antagonistic activity. Org Biomol Chem.
2005;3:2129-39.
2. Fahy E, Subramaniam S, Brown HA, Glass CK,
Merrill AH, Jr., Murphy RC, et al. A
comprehensive classification system for lipids. J
Lipid Res. 2005;46:839-61.
3. Houjou T, Yamatani K, Imagawa M, Shimizu T,
Taguchi R. A shotgun tandem mass spectrometricanalysis of phospholipids with normal-phase
and/or reverse-phase liquid chromatography/
electrospray ionization mass spectrometry. Rapid
Commun Mass Spectrom. 2005;19:654-66.
4. Iizuka Y, Yokomizo T, Terawaki K, Komine M,
Tamaki K, Shimizu T. Characterization of a mousesecond leukotriene B4 receptor, mBLT2:
BLT2-dependent ERK activation and cell
migration of primary mouse keratinocytes. J Biol
Chem. 2005;280:24816-23.
5. Ishii S, Kihara Y, Shimizu T. Identification of T
cell death-associated gene 8 (TDAG8) as a novel
acid sensing G-protein-coupled receptor. J Biol
Chem. 2005;280:9083-7.
6. Kihara Y, Ishii S, Kita Y, Toda A, Shimada A,
Shimizu T. Dual phase regulation of experimental
allergic encephalomyelitis by platelet-activating
factor. J Exp Med. 2005;202:853-63.
7. Kita Y, Takahashi T, Uozumi N, Nallan L, Gelb

11

MH, Shimizu T. Pathway-oriented profiling oflipid mediators in macrophages. Biochem Biophys
Res Commun. 2005;330:898-906.
8. Kita Y, Takahashi T, Uozumi N, Shimizu T. A
multiplex quantitation method for eicosanoids andplatelet-activating factor using column-switching
reversed-phase liquid chromatography-tandem
mass spectrometry. Anal Biochem. 2005;342:13443.
9. Lang PA, Kempe DS, Tanneur V, Eisele K, Klarl
BA, Myssina S, et al. Stimulation of erythrocyte
ceramide formation by platelet-activating factor. J
Cell Sci. 2005;118:1233-43.
10. Marusic S, Leach MW, Pelker JW, Azoitei ML,
Uozumi N, Cui J, et al. Cytosolic phospholipase
A2α-deficient mice are resistant to experimental
autoimmune encephalomyelitis. J Exp Med. 2005;
202:841-51.
11. Ohto T, Uozumi N, Hirabayashi T, Shimizu T.
Identification of novel cytosolic phospholipase
A2s, murine cPLA2δ, ε, and ζ, which form a genecluster with cPLA2β. J Biol Chem. 2005;280:
24576-83.
12. Oikawa Y, Yamato E, Tashiro F, Yamamoto M,
Uozumi N, Shimada A, et al. Protective role forcytosolic phospholipase A2α in autoimmune
diabetes of mice. FEBS Lett. 2005;579:3975-8.
13. Okuno T, Yokomizo T, Hori T, Miyano M,
Shimizu T. Leukotriene B4 receptor and thefunction of its helix 8. J Biol Chem. 2005;280:32049-52.
14. Saiga A, Uozumi N, Ono T, Seno K, Ishimoto Y,
Arita H, et al. Group X secretory phospholipase
A2 can induce arachidonic acid release andeicosanoid production without activation ofcytosolic phospholipase A2α. Prostaglandins
Other Lipid Mediat. 2005;75:79-89.
15. Shimada A, Satoh M, Chiba Y, Saitoh Y,
Kawamura N, Keino H, et al. Highly selective
localization of leukotriene C4 synthase in
hypothalamic and extrahypothalamic vasopressin
systems of mouse brain. Neuroscience. 2005;131:
683-9.
16. Shindou H, Ishii S, Yamamoto M, Takeda K,
Akira S, Shimizu T. Priming effect oflipopolysaccharide on acetyl-coenzyme A:lysoplatelet-activating factor acetyltransferase is

MyD88 and TRIF independent. J Immunol. 2005;
175:1177-83.
17. Taguchi R, Houjou T, Nakanishi H, Yamazaki T,
Ishida M, Imagawa M, et al. Focused lipidomics
by tandem mass spectrometry. J Chromatogr B
Analyt Technol Biomed Life Sci. 2005;823:26-36.
18. Taniguchi M, Masuda T, Fukaya M, Kataoka H,
Mishina M, Yaginuma H, et al. Identification andcharacterization of a novel member of murine
semaphorin family. Genes Cells. 2005;10:785-92.
19. Terawaki K, Yokomizo T, Nagase T, Toda A,
Taniguchi M, Hashizume K, et al. Absence of
leukotriene B4 receptor 1 confers resistance toairway hyperresponsiveness and Th2-type
immune responses. J Immunol. 2005;175:421725.
20. Toyo-Oka K, Sasaki S, Yano Y, Mori D,
Kobayashi T, Toyoshima YY, et al. Recruitment ofkatanin p60 by phosphorylated NDEL1, an LIS1
interacting protein, is essential for mitotic cell
division and neuronal migration. Hum Mol Genet.
2005;14:3113-28.
21. Zhang Q, Mousdicas N, Yi Q, Al-Hassani M,
Billings SD, Perkins SM, et al. Staphylococcal
lipoteichoic acid inhibits delayed-type hypersensitivity reactions via the platelet-activating
factor receptor. J Clin Invest. 2005;115:2855-61.
22. Kita Y, Ohto T, Uozumi N, Shimizu T. Biochemical properties and pathophysiological roles ofcytosolic phospholipase A2s. Biochim Biophys
Acta 2006; 1761: 1317-22.
23. Akiba S, Mukaida Y, Hane K, Oka M, Uozumi N,
Shimizu T, Sato T. Group IVA phospholipase A(2)-mediated production of fibronectin by oxidized
LDL in mesangial cells. Kidney Int. 2006; 70:1013-18.
24. Shimizu T, Ohto T, Kita Y. Cytosolic
phospholipase A2: Biochemical properties andphysiological roles. IUBMB Life 2006; 58: 328-33.
25. Chiba Y, Shimada A, Satoh M, Saitoh Y,
Kawamura N, Hanai A, Keino H, et al. Sensory
system-predominant distribution of leukotriene a(4)hydrolase and its colocalization with calretinin in
the mouse nervous system. Neurosci. 2006; 141:917-27.
26. Nakanishi H, Shindou H, Hishikawa D, Harayama
T, Ogasawara R, Suwabe A, et al. Cloning and12characterization of mouse lung-type acyl-coa:lysophosphatidylcholine
acyltransferase
1(LPCAT1): Expression in alveolar type II cells, andpossible involvement in surfactant production. J
Biol Chem. 2006; 281: 20140-7.
27. Yoshikawa K, Kita Y, Kishimoto K, Shimizu T.
Profiling of eicosanoid production in the rat
hippocampus during kainate-induced seizure:Dual-phase regulation and differential involvementof cox-1 and cox-2. J Biol Chem. 2006; 281:
14663-9.
28. Doi K, Okamoto K, Negishi K, Suzuki Y, Nakao A,
Fujita T, et al. Attenuation of folic acid-induced
renal inflammatory injury in platelet-activating
factor receptor-deficient mice. Am J Pathol. 2006;
168: 1413-24.
29. van der Sluijs KF, van Elden LJR, Nijhuis M,
Schuurman R, lorquin S, Shimizu T, et al.
Involvement of the platelet activating factor
receptor in host defense against Streptococcus
pneumoniae during postinfluenza pneumonia. Am J
Physiol. 2006; 290: L194-9.

13

Department of Physiological
Chemistry and Metabolism
Professor
Hiroki Kurihara, M.D.

Research Associate
Yukiko Kurihara, M.D.,

Kouichi Nishiyama, M.D.

Associate
Yasunobu Uchijima, Ph.D.

URL

http://bio.m.u-tokyo.ac.jp/home-j.html

Introduction and Organization
The Department of Physiological Chemistry andNutrition, the predecessor of the present department,
was founded in 1952. Upon the restructuring of theuniversity system in 1997, the department was
renamed ‘Department of Physiological Chemistry andMetabolism’ as one unit of the Specialty of Molecular
Cell Biology. The present members include the above
stuffs, 2 postdoctoral fellows, 1 visiting scientist, 10
graduate students (8 doctoral course, 2 master’scourse). We are also working together with theEndowment Department of Developmental andMedical Technology (Sankyo) in research andeducation.

Teaching Activities
We give a series of lectures and laboratory courses
on biochemistry and molecular biology forundergraduate students from Faculty of Medicine andFaculty of Science. We also accept undergraduate
students taking “Free Quarter” and “Early-Exposureto-Medicine” courses every year. Several students arestaying in our lab beyond the term to join our research.
For graduate students, we hold progress-reportmeeting and journal club every week, and sometimes
invite established scientists for seminar to encourage

scientific discussion.

Research Activities
1. Developmental Biology and Medicine(1) Neural crest and craniofacial development
We have investigated the role of endothelin-1(ET-1) signaling in neural crest and craniofacial
development and identified the ET-1/ETA-receptor
to Dlx5/6 pathway in the dorsoventral axis
patterning of crest-driven branchial arch structures.
We also identified Calpain6 as a downstream
molecule of the ET-1 pathway and its biological
function in cytoskeletal organization and cell
motility. We further identified TAZ as a protein thatbinds to and coactivates Pax3, a key transcription
factor in neural crest development and its role in theorganogenesis of the kidney and lung as revealed bygene knockout.
(2) Preimplantation development and epigenetics
To further understand the mechanisms of celldifferentiation, we are studying how the DNA
methylation status is controlled in preimplantation
development and how reprogramming occurs after
nuclear transfer. We identified the somatic type of
DNA methyltransferase 1 as an enzyme responsible
for maintenance methylation in preimplantation
development.

14(3) Angiogenesis
We found that Id1 confers in vivo angiogenic
property to human vascular endothelial cells via
angiopoietin-1 upregulation, which may give a clue
to novel strategy for therapeutic angiogenesis. We
also found that the function of Id1 is controlled byprotein kinase A through nucleoplaasmic shuttling.
2. Metabolism
We are collaborating with Professor Tomoichiro
Asano (Hiroshima University, formerly Associate
professor of this department) and Associate Professor
Shin-ichiro Takahashi (Graduate School of Agricultureand Life Sciences, The University of Tokyo) in insulinmediated metabolism and underlying molecularmechanisms. In particular, intracellular insulin
signaling, novel Akt-associated proteins, resistin-likemolecules, and are foci of the present investigations.

References (2006)
1. Murakami, M., Tominaga, J., Makit, R., Uchijima,Y., Kurihara, Y., Nakagawa, O., Asano, T. andKurihara, H. (2006). Transcriptional activity of
Pax3 is co-activated by TAZ. Biochem Biophys
Res Commun 339:533-539.
2. Amano, T., Gertsenstein, M., Nagy, A., Kurihara,
H. and Suzuki, H. (2006). Nuclear transfer
reprogramming does not improve the low
developmental potency of embryonic stem cells
induced by long-term culture. Reproduction 132:257-263.
3. Viana, A. Y., Sakoda, H., Anai, M., Fujishiro, M.,
Ono, H., Kushiyama, A., Fukushima, Y., Sato, Y.,
Oshida, Y., Uchijima, Y., Kurihara, H. and Asano,T. (2006). Role of hepatic AMPK activation in
glucose metabolism and dexamethasone-induced
regulation of AMPK expression. Diabetes Res
Clin Pract 73:135-142.
4. Harada, N., Okajima, K., Uchiba, M., Kurihara, H.
and Nakagata, N. (2006). Antithrombin reduces
reperfusion-induced liver injury in mice byenhancing sensory neuron activation. Thromb
Haemost 95:788-795.
5. Shimozawa, N., Okajima, K., Harada, N., Arai, M.,
Ishida, Y., Shimada, S., Kurihara, H. and Nakagata,N. (2006). Contribution of sensory neurons to sex

difference in the development of stress-induced
gastric mucosal injury in mice. Gastroenterology
131:1826-1834.
6. Cho Y, Ariga M, Uchijima Y, Kimura K, Rho JY,
Furuhata Y, Hakuno F, Yamanouchi K, Nishihara
M, Takahashi SI. (2006) The Novel Roles of Liverfor Compensation of Insulin Resistance in Human
Growth Hormone Transgenic Rats. Endocrinology
147, 5374-5384.

16

Department of Integrative
Physiology
Professor
Yasushi Miyashita, Ph.D.

Associate Professor
Seiki Konishi, M.D., Ph.D.

Associate
Tetsuya Fukushima, M.D., Ph.D.,

Toshiyuki Hirabayashi, Ph.D.,

Masaki Takeda, Ph.D.

Homepage

http://www.physiol.m.u-tokyo.ac.jp

Introduction
This laboratory was initially established in 1877 as
The First Department of Physiology, and reorganizedin 1997 as Laboratory of Integrative Physiology in the
Department of Physiology. Our laboratory cooperates
with other laboratories in the Department of Physiology, that is, Laboratory of Molecular/Cellular Physiology and Laboratory of Neurophysiology, in teachingactivities for undergraduate courses and the nursing
school. The fields in which our laboratory specializes
span the entire spectrum of animal functions of physiology, including general physiology, sensory physiology, endocrinology, neurophysiology, higher nervous
functions and cognitive neurosciences.

Teaching activities
The staff members as well as experts from otheruniversities (Drs. A. Nambu, K. Honma and I. Hasegawa) take part in giving lectures and laboratory
courses to the undergraduate students of the Medical
School. The lectures are aimed at providing a clear
understanding of the hierarchical functional organizations of living systems. The curriculum is updated
every year. For example, a new electrocardiogram
experiment in humans was introduced to the labora-

tory course, which gained popularity and interest
among students. We accept Free-Quarter students
every year. Usually these students' activities are notlimited to one Quarter, and 2 students (M2 and M3)
continued to enjoy their research from 2006 through2007. Some of these students completed their own
projects, and gave oral presentations in international
meetings and published original papers in top-rankinternational journals. A student who enjoyed his
Free-Quarter decided to get into the Ph-D.-M.D
course and started to study neurophysiology in ourlaboratory. Thus the Free-Quarter system has proved
to be an excellent guide for the Ph-D.-M.D course.
To facilitate communication among research groups
in our laboratory, a weekly conference is held for discussing current research activities. We also have amonthly joint seminar with Department of Pharmacology, Department of Psychology in Faculty of Letters and Department of Biophysics in Faculty of Science. As part of a teaching activity for the graduate
students, we have another weekly English seminar, inwhich the graduate students learn how to give presentations and hold discussions and debates in English.

17

Research activities
Most of our research is focused on the higher brain
function of the mammalian central nervous system :(1) higher functions of vision and memory, (2)non-invasive measurements of human brain activitiesand (3) non-invasive functional measurements ofmonkey brain activities that links above (1) and (2).
The results of such research have been published infirst-rate journals, as listed in the reference. A briefsummary of each topic follows:(1) In the primate, visual information processing in
the cerebral cortex proceeds along the neuralpathway originating from the primary visual areain the occipital lobe to the anterior part of thetemporal association cortex. Our laboratory discovered several classes of important memory-neurons electrophysiologically in the temporal lobe of the monkey. In the inferotemporal
cortex, which we propose to be the storehouse ofvisual long-term memory, we discovered a groupof neurons which encode object-object association. We found that the backward signal from themedial temporal lobe to the inferotemporal cortex
mediates formation of the mnemonic neural circuits for the association. Recently we also foundthat the top-down signal from the prefrontal cortex to the inferotemporal cortex plays a central
role in retrieval of the mnemonic associative
neural code stored in the inferotemporal cortex.
Since association is a basic mechanism for constructing the human memory-based knowledge
system, our finding provides a key to understanding the basic organization of the primate cerebral cortex.
(2) The recent explosion of new technologies fornoninvasive measurements of human brain activities, especially of functional magnetic resonance imaging (fMRI), allows us to observe parallel activation of functional brain modules inhumans engaged in various mental tasks. We
contributed to development of a new method
called “event-related fMRI”, which enables toutilize the time resolution of fMRI. We applied
this “event-related fMRI” method to the analysis
of human cognition, and identified several functional centers in the human prefrontal cortex incognitive tasks such as the Wisconsin Card Sorting Task.
(3) Recently, we successfully applied fMRI method
to macaque monkeys performing highly intelligent cognitive tasks. These fMRI studies weredone in ultra-high field MRI scanner at 4.7 Tesla,
successfully providing much higher spatial resolution than in a conventional clinical MRI scanner.
This approach provides us a new approach thatbridges a gap between the human non-invasive
studies and the various invasive studies in animals, including intra-cortical electrical microstimulation and reversible functional inactivation
with GABA agonist drug injections.

References
1. Matsui, T., Koyano, K.W., Koyama, M., Nakahara,K., Takeda, M., Ohashi, Y., Naya, Y. and Miyashita, Y. : MRI-based localization of electrophysiological recording sites within the cerebral
cortex at single voxel accuracy. Nature methods 4,
161-168, 2007.
2. Chikazoe, J., Konishi, S., Asari, T., Jimura, K.
and Miyashita, Y.: Activation of right inferior
frontal gyrus during response inhibition acrossresponse modalities. J. Cogn. Neurosci. 19,
69-80, 2007.
3. Nakahara, K., Adachi, Y., Osada, T. and Miyashita Y : Exploring the neural basis of cognition:
multi-modal links between human fMRI and macaque neurophysiology. Trend Cogn. Science 11,84-92, 2007.
4. Konishi, S., Asari, T., Jimura, K., Chikazoe, J.
and Miyashita, Y. : Activation shift from medial
to lateral temporal cortex associated with recency
judgements following impoverished encoding.
Cereb. Cortex 16, 469-474, 2006.
5. Takeda, M., Naya, Y., Fujimichi, R., Takeuchi, D.
and Miyashita, Y. : Active maintenance of associative mnemonic signal in monkey inferior temporal cortex. Neuron 48, 839-848, 2005.
6. Konishi, S., Chikazoe, J., Jimura, K., Asari, T.
and Miyashita, Y. : Neural mechanism in anterior
prefrontal cortex for release from inhibition of

18

prolonged set interference. Proc. Natl. Acad. Sci.
USA 102, 12584-12588, 2005.

19

Department of Cellular andMolecular Physiology
Professor
Kensaku Mori, Ph.D.

Lecturer
Masahiro Yamaguchi, M.D., Ph.D.

Associate
Hiroshi Nagao, Ph.D.,

Homepage

Hideki Kashiwadani, Ph.D.

http:// morilab.m.u-tokyo.ac.jp/

Introduction

Research

The Department of Cellular and Molecular
Physiology succeeded the former ‘Second Departmentof Physiology’, and belong to the Department of
Physiology. We participate in the teaching ofphysiology at undergraduate school and graduate
school.
The present members include the above stuffs, 1 visiting scientist, 12 graduate students and 1 secretary.

Using multidisciplinary approaches including electrophysiology, optical imaging, molecular and cellularbiology, and molecular genetics, we at the Department
of Cellular and Molecular Physiology aim at understanding neuronal mechanism for the perception of
sensory inputs and for the emotional states induced by
the sensory inputs. Our recent focus includes olfactory
cortical mechanisms for recognizing food odors andfor judging their edibility.
We have been investigating also the neuronal mechanisms for the incorporation of adult-born interneurons into the pre-existing neuronal circuit in theolfactory bulb, and the contact-mediated interactions
between neurons and immune cells.
Currently we are focusing on the following three
topics.

Education
The department provides lectures and practice inphysiology for undergraduate students. We teach electrophysiological methods and cell and molecular physiology methods for free quarter students. The department provides also lectures and instructions forlaboratory research for graduate and undergraduate
students in the fields of sensory physiology and molecular and cellular neurobiology. Seminars, progress
reports, and journal club for graduate students areroutinely provided. Monthly joint seminars (Functional Biology Seminars and RIKEN BSI Group
Seminars) are also provided for graduate students.

(1) Analysis of the functional neuronal circuits in thecentral olfactory system.
Based on the knowledge of the ‘odorant receptor
maps’ in the olfactory bulb, we are studying themanner of olfactory information processing in theolfactory cortex and higher olfactory association
regions. We found that individual neurons in theanterior piriform cortex integrate signals fromdistinct categories of food-born odorants. These20

results suggest that the olfactory cortical neurons
detect the odorant-category profile of foods in order to distinguish distinct food odors.
Individual neurons in the anterior olfactory nucleus also showed odorant category profile selectivity. Furthermore, for individual cortical neurons
odorant category profile selectivity of left-nasal
input was nearly equivalent with that of theright-nasal input.
We found also that neuronal circuit in the olfactory bulb can actively prolong the odor induced
spike responses and thus keep the specific odor
information for more than tens of seconds after
the cessation of odor stimulus. In addition, we
noted behavioral state-dependent change of thedendrodendritic synaptic inhibition in the olfactory bulb.
(2) Cellular and molecular mechanisms for the contact-mediated interactions between neurons andimmune cells in physiological and pathologicalconditions.
We are currently focusing on telecncephalonspecific cell adhesion molecule, telencephalin. We
found that damage on hippocampal CA1 area
caused by local injection of kainic acid increased
density and area of contacts between activatedmicroglia and the dendrites of CA1 pyramidal
neurons. We are further investigating the telencephalin-mediated signals between neurons andimmune cells during recovery from the neuronaldamage.
(3) Incorporation of adult-born interneurons in the
pre-existing neuronal circuit in the olfactory bulb.
The olfactory system is chosen as a model systemwith which to study the recruitment of newlygenerated neurons in the adult neuronal circuit.
We are studying cellular and molecular mechanisms that segregate the fate of new neurons between successful incorporation and apoptotic elimination into/from the neuronal circuit. Recently
we noted the feeding-related time window of fatedecision of newly-generated granule cells in theolfactory bulb, and current focus of our study includes the reorganization of the olfactory bulb
circuit during and after the eating time.

Publications (2006-)
1. Mori K, Takahashi YK, Igarashi KM, Yamaguchi
M. Maps of odorant molecular features in the
mammalian olfactory bulb. Physiological Reviews
86:409-433 (2006)
2. Imamura F, Nagao H, Naritsuka H, Murata Y, Taniguchi H, Mori K. A leucine-rich repeat membrane protein 5T4 is expressed by a subtype of
granule cells with dendritic arbor in specific strataof the mouse olfactory bulb. J. Comp. Neurol.
495:754-768 (2006)
3. Xu Y, Kitada M, Yamaguchi M, Dezawa M, Ide C.
Increase in bFGF-responsive neural progenitor
population following contusion injury of the adultrodent spinal cord. Neurosci. Lett. 397:174-179(2006)
4. Kunze A, Grass S, Witte OW, Yamaguchi M,
Kempermann G, Redecker C. Proliferative response of distinct hippocampal progenitor cell
populations after cortical infarcts in the adultbrain. Neurobiol. Dis. 21:324-332 (2006)
5. Takagi T, Jin W, Taya K, Watanabe G, Mori K,
Ishii S. Schunurri-2 mutant mice are hypersensitive to stress and hyperactive. Brain Res. 1108:
88-97 (2006)
6. Matsuno H, Okabe S, Mishina M, Yanagida T,
Mori K, Yoshihara Y. Telencephalin slows spine
maturation. J. Neurosci. 26:1776-1786 (2006)
7. Mitsui S, Saito M, Mori K, Yoshihara Y. A transcription enhancer that directs telencephalon-specific transgene expression in mouse brain.
Cerebral Cortex 17: 522-530 (2007)
8. Hasegawa, S., Yamaguchi, M., nagao, H., Mishina,
M and Mori, K. Enhanced cell-to-cell contacts
between activated microglia and pyramidal cell
dendrites following kainic acid-induced neurotoxicicity in the hippocampus. J. Neuroimmunol. 186:
75-85 (2007)

21

Department of Neurophysiology
Professor
Tomoyuki Takahashi, M.D., Ph.D.

Lecturer
Tetsuhiro Tsujimoto, M.D., Ph.D.

Naoto Saitoh, Ph.D.

Associate
Tetsuya Hori, Ph.D.

Home page

http://square.umin.ac.jp/nphystk

Introduction and organization
Our laboratory was founded in 1953 as Departmentof Neurophysiology, Institute for Brain Research. In
1996 it was integrated into Graduate School of Medicine. We teach neurophysiology for medical undergraduates and for students in the Master and Ph.D.
courses. Our research is aimed at elucidating cellularand molecular mechanisms underlying synaptictransmission.

Teaching activities
We teach medical undergraduates in lectures and apractical course. Lectures are designed for students tolearn basic mechanisms underlying electrical signals,
how they are generated and propagated through nerve
fibers and across synapses. Students also learn dynamic aspects of synaptic efficacy underlying diverse
brain functions such as memory and consciousness. A
couple of months before lectures students in 20 groups
are given key words with references to prepare asummary sheet, upon which each group presents a
short talk in a class. Their talks are followed by discussions and supplementary lectures by professor.
During the procedure of preparing summary sheets,
students make discussions with professor. In practicalcourse, students are encouraged to make patch-clamp
recordings from neurons visually identified in brainslices. In this course, students learn how electricalsignals are made of ion channel currents. In separate

set-ups, students record field synaptic potentials fromhippocampal slices and learn how to induce short-termand long-term synaptic plasticities. Trainings for the
Master and PhD course students are made regularly on
Monday in the forms of progress reports and journal
clubs, where students and staffs summarize topics andalso classics in physiology and neuroscience.

Research Activities
In mammalian CNS, after synaptic contacts areformed in fetal period, synapses undergo morphological, functional and molecular changes during postnatal
development, toward establishment of mature synapses differentiated into various neuronal functions.
Our research aim is to clarify causal molecular-functional relationship, thereby elucidating molecular mechanisms underlying synaptic transmission
and modulation. In brainstem slices of rodents, a giant
nerve terminal, called the calyx of Held, can be visually identified. We make simultaneous presynaptic andpostsynaptic whole-cell recordings from the calyces
and target cells in developing rodents, and makeanalysis on synaptic transmission. With this recording
we combine (i) presynaptic capacitance measurements
for assessing synaptic vesicle exo/endocytosis, (ii)infusion of drugs or inhibitor proteins into the terminal, (iii) Ca measurements. In addition we make (iv)
immunocytochemical examinations for protein expressions in the calyceal terminals, (v) use knockout
mice to establish causal molecular-function relation-

22

ships, and (vi) make bilateral cochlear ablations toinvestigate whether newly found developmental
change depends upon hearing input activity. Our present subjects of research are clarifications of mechanisms underlying (1) vesicle recycling and reuse, (2)transmitter release probability, (3) facilitation oftransmitter release, (3) high-fidelity synaptic transmission.

References (2006-2007)
1. Mizutani H., Hori T., & Takahashi T. (2006).
5-HT1B receptor-mediated presynaptic inhibitionat the calyx of Held of immature rats.
Eur.J.Neurosci. 24, 1946-1954.
2. Hige T., Fujiyoshi Y., & Takahashi T. (2006).
Neurosteroid pregnenolone sulfate enhances glutamatergic synaptic transmission by facilitatingpresynaptic calcium currents at the calyx of Heldof immature rats. Eur.J.Neurosci. 24, 1955-1966.
3. Nakamura Y. & Takahashi T. (2007). Developmental changes in potassium currents at the rat
calyx of Held presynaptic terminal. J. Physiol.
581, 1101-1112.

24

Department of Cellular
and Molecular Pharmacology
Professor
Masamitsu Iino, M.D., Ph.D.

Associate
Toshiko Yamazawa, Ph. D.,

Sho Kakizawa, Ph. D.

Yohei Okubo, Ph. D.

Homepage

http://calcium.cmp.m.u-tokyo.ac.jp/

Introduction and Organization
Our department was founded in 1885 andcollaborates with the Department of Molecular
Neurobiology and Pharmacology in the education ofundergraduate medical students.

Teaching activities
Pharmacology lectures and laboratory courses forthe medical students are given by the staff members ofboth Departments of Pharmacology. We also invite
seven outside expert lecturers to cover rapidly
developing fields in pharmacology and related
medical sciences. The laboratory courses include bothtraditional and advanced pharmacological experiments.
A new intensive laboratory course for medical
students started in the year 2001, and we participatedin the program. We also give lectures for graduate
students including master course students and Ph.D.
candidates.

Research activities
Our department has a strong background in the fieldof Ca2+ signalling. Ca2+ signal is now known tofunction as a molecular switch in almost every
important cell function including muscle contraction,
exocytosis, cell proliferation, immune responses andregulation of synaptic functions. This is the reason
why this field is expanding rapidly and our research
activity is now diversifying. We are particularlyinterested in Ca2+ signalling in the central nervous
system.
1) Spatiotemporal regulation of Ca2+ signals
Ca2+ signals show very dynamic, temporal andspatial changes. This property allows the Ca2+
signal to be an extremely versatile cellular switch
regulating diverse cell functions. One of the mostnotable spatiotemporal patterns of Ca2+ signals is
the oscillatory change in intracellular Ca2+
concentration ([Ca2+]i), or Ca2+ oscillation. Many
cellular functions are regulated by the Ca2+
oscillation frequency. However, fundamental
questions remain. How and why does [Ca2+]i
oscillate? We have addressed these questions. First,
we studied inositol 1,4,5-trisphosphate (IP3)induced Ca2+ release mechanism, which is one of
the most important Ca2+ mobilizing mechanisms inmany types of cell. We showed that the activity of
the IP3 receptor (IP3R) is dependent on thecytoplasmic Ca2+ concentration. Therefore, Ca2+
release via the IP3R appears to be under the
feedback control of mobilized Ca2+. We identified
the Ca2+ sensor region of the IP3R and showed thatthe positive feedback regulation of IP3R via theCa2+ sensor of IP3R indeed plays an essential role
in regulating the Ca2+ signal dynamics including

25

Ca2+ oscillation.
In order to further study the mechanism
underlying Ca2+ oscillations, we visualized theCa2+ concentrations within the intracellularorganelles (the endoplasmic reticulum andmitochondria) during Ca2+ oscillations. We foundthat Ca2+ shuttles between these intracellularorganelles in phase with cytoplasmic Ca2+
oscillations. Our results also indicated that theCa2+ shuttling determines the Ca2+ oscillation
frequency. Thus, we have shown that mitochondria
play an important role in the generation of Ca2+
oscillation. These results provide a clue to themechanism of Ca2+ oscillation.
Why then does [Ca2+]i have to oscillate?
Transcription by the nuclear factor of activated T
cells (NFAT) is one of the important cellularfunctions that are regulated by the Ca2+ oscillation
frequency. NFAT is dephosphorylated by
Ca2+-dependent phosphatase, calcineurin, andtranslocates from the cytoplasm to the nucleus toinitiate transcription. We analyzed the kinetics ofthe dephosphorylation and translocation of NFAT,
and found that the dephosphorylated form of
NFAT functions as a working memory of transient
increases in [Ca2+]i. With increasing frequency ofCa2+oscillation,dephosphorylated
NFAT
accumulates in the cytoplasm to enhance its
nuclear translocation. This is the molecular basisof the mechanism that decodes the Ca2+ oscillation
frequency. We also showed that Ca2+ oscillation ismore cost-effective in regulating cell functions
than a continuous increase in Ca2+. These studies
provide us with an insight into the secrets of Ca2+
signalling.

The indicator allowed us to image phosphorylation
state of myosin light chain in living cells. Recently,
we generated a nitric oxide (NO) indicator basedon the heme-binding domain of soluble guanylyl
cyclase. This indicator was successfully used in
cerebellar slice preparations to image NO signals
in response to parallel fiber (PF) stimulation. We
found that the NO signal intensity decreases
steeply with distance form the activated synapse
andgenerate
synapse-specificlong-term
potentiation (LTP) of PF-Purkinje cell synapses.
We also showed that the NO signal intensity
depends biphasically on the frequency of PF
stimulation. Importantly, the LTP depends
similarly on the frequency of PF stimulation. Thus,
our NO indicator provided us with valuable
information regarding the role of NO signals in thecentral nervous system.
Cells communicate with each other to form
organized structures by cell-cell adhesion andcell-cell repulsion, but it remains to be clarified
how cell-cell contact information is converted to
intracellular signals. We found that cells in contact
with neighbouring cells generate local transient
intracellular Ca2+ signals (Ca2+ lightning). Ca2+
lightning was exclusively observed near cell-cell
contact regions and was not observed in the central
regions of cells, nor was it found in solitary cells
that are not in contact with other cells. We also
show that Ca2+ lightning is capable of regulatingcell-cell repulsion in a Ca2+-dependent manner.
These results demonstrated that cell-cell contact
information may be transmitted by a new form of
Ca2+ signal, Ca2+ lightning, to regulate
intracellular events.

2) Imaging of signalling molecules
Our study on Ca2+ signalling made us realize theimportance of visualization of signalling
molecules within living cells. Thus, our laboratory
has been involved in the generation of new
indicators of signalling molecules upstream anddownstream Ca2+ signals. We have succeeded in
imaging IP3 signalling in various cells including
intact neurons within cerebellar slice preparations.
We also developed an indicator to detect thephosphorylation of myosin regulatory light chain.

3) Exploration of new cellular functions that are
regulated by Ca2+ signals
Although many important cell functions havebeen found to be regulated by Ca2+ signals, not all
the Ca2+-dependent cell functions have been
identified. We are now searching for new cellfunctions that are regulated by Ca2+ signals. Oneof such attempts has clarified a new synaptic
maintenance mechanism in the parallel fiber→
Purkinje cell synapse in the cerebellum. We havefound that there is a retrograde signaling

26

mechanism
downstreamofmetabotropic2+
glutamate receptor-mediated IP3-Ca signaling in
Purkinje cells, which then generates BDNF
(brain-derived neurotrophic factor) that maintains
the glutamate-release function of the presynaptic
terminal of parallel fibers. This presents a newform of activity-dependent synaptic maintenancemechanism. We are trying to extend our effort tofind new Ca2+-dependent cell functions.

References
1.

Ishii K, Hirose K, Iino M. Ca2+ shuttling between
endoplasmic

reticulum

underlying

2+

Ca

and

oscillations.

mitochondria
EMBO

Rep

2006;7:390-6.
2.

Furutani K, Okubo Y, Kakizawa S. Iino M.
Postsynaptic

inositol

1,4,5-trisphosphatesignaling maintains presynaptic function ofparallel fiber-Purkinje cell synapses via BDNF.
Proc Nat Acad Sci USA 2006;103:8528-33.
3.

Hashido M, Hayashi K, Hirose K, Iino M. Ca2+
lightning conveys cell-cell contact information
inside the cells. EMBO Rep 2006;7:1117-23.

4.

Baba Y, Hayashi K, Fujii Y, Mizushima A,
Watarai H, Wakamori M, Numaga T, Mori, Y,
Iino M. Hikida M, Kurosaki T. Coupling of
STIM1 to store-operated Ca2+ entry through its
constitutive and inducible movement in theendoplasmic reticulum. Proc Nat Acad Sci USA
2006;103:16704-9.

5.

Iino

M.

Ca2+-dependent

inositol

1,4,5-

trisphosphate and nitric oxide signaling in
cerebellar neurons. J Pharmacol Sci 2006;100:538-44.

27

Department of
Molecular Neurobiology
Professor
Masayoshi Mishina, Ph.D.

Associate
Tomonori Takeuchi, Ph.D.,

Tomoyuki Yoshida, Ph.D.,

Takashi Uemura, Ph.D.,

Kazuto Nakao, Ph.D.

Homepage

http://www.pharmacol2.m.u-tokyo.ac.jp/

Teaching activities
Our Department, in collaboration with the
Department of Cellular and Molecular Pharmacology,
takes responsibility for lectures and laboratory courses
on pharmacology for the undergraduate students of theFaculty. There are some 41 lectures per year including
those given by seven invited lectures to cover
specialized and currently highlighted fields inpharmacology. We offer several laboratory courses,
and all the members of the Department participate in
the courses to provide close consultation for the
students.
For the graduate students, there are series ofseminars on molecular biology and neuroscience. We
also have research seminars to discuss and stimulate
the research activities of the graduate students in the
Department.

Research activities
Current research activities are focused on themolecular basis of learning and memory. As an initialstep, we have elucidated the molecular diversity of the
NMDA-type glutamate receptor (GluR) channel thatplays a key role in synaptic plasticity as a molecularcoincidence detector. Combination of the GluRε and
GluRζ subunit families is essential for the formation
NMDA-type GluR channels. The four glutamate-binding GluRε subunits are distinct in distribution,functional properties and regulation. Thus, multiple
GluRε subunits are major determinants of the NMDA
receptor channel diversity, and the molecularcompositions and functional properties of NMDA
receptor channels are different depending on the brain
regions and developmental stages. We generated
mutant mice defective in respective GluRε subunits bygene targeting. We have shown that disruption of the
GluRε1 subunit results in the increase of thresholds
for both hippocampal LTP and contextual learning.
The GluRε2 subunit mutant mice showed the
impairment of the formation of the whisker-related
neuronal barrelette structure in the brainstemtrigeminal nucleus. We found the GluRδ subunit
family, a novel member of the GluR channel family,
by cloning. The GluRδ2 subunit is selectively
localized in cerebellar Purkinje cells. Analyses of the
GluRδ2 mutant mice reveal that the δ2 subunit plays
important roles in the motor coordination, theformation of parallel fiber-Purkinje cell synapses andclimbing fiber-Purkinje cell synapses, and thelong-term depression of parallel fiber-Purkinje cell
synaptic transmission. These findings have led ourcurrent hypothesis that the activity-dependent synapse
refinement during neural development and thelearning and memory in adult brain share the common
molecular mechanism.
To verify this proposal, we are employing two

28

approaches. One is the forward genetic approach inzebrafish to systematically screen the key moleculesof the formation and dynamic changes of synapses.
We developed a highly efficient deletion mutagenesis
in zebrafish and isolated mutant zebrafish with defects
in neural development. Current efforts are on theefficient cloning of the mutant genes. The otherapproach is the reverse genetics with mice. To
examine the functional roles of developmentally
important molecules in higher brain functions and toseek for engram, we are developing the stage- andbrain region-specific conditional targeting. The wealthof knowledge on the neural circuits makes the
cerebellum an ideal system to study the molecularmechanism of brain function. To develop a cell
type-specific and temporal regulation system of genetargeting in the cerebellum, we employed the
NMDA-type glutamate receptor GluRε3 subunit gene
and Cre recombinase-progesterone receptor fusion(CrePR) gene in combination. Injection of the CrePR
fusion gene placed under the control of the 10 kb 5’
region of the GluRε3 gene into C57BL/6 eggs yielded
the ECP25 line that strongly expressed the CrePR
mRNA selectively in the granule cells of thecerebellum. Using a transgenic mouse carrying areporter gene for Cre-mediated recombination, we
showed that antiprogestins could induce therecombinase activity of CrePR fusion protein in the
cerebellar granule cells of the ECP25 line. Thus, theestablished mouse line will provide a valuable tool toinvestigate the mechanism of cerebellar function by
manipulating molecules in the temporally regulated
and granule cell-specific manner

References
1. Matsuno H, Okabe S, Mishina M, Yanagida T,
Mori K, Yoshihara Y. Telencephalin slows spine
maturation. J. Neurosci. 2006; 26: 1776-1786.
2. Kitamura, T., Mishina, M. and Sugiyama, H. Dietary
restriction increases hippocampal neurogenesis bymolecular mechanisms independent of NMDA
receptors. Neurosci. Lett. 2006; 393, 94-96.
3. Kakegawa, W., Miyzaki, T., Hirai, H., Motohashi, J.,
Mishina, M., Watanabe, M. and Yuzaki, M. Ca2+
permeability of the channel pore is not essential for theδ2 glutamate receptor channel to regulate synaptic

plasticity and motor coordination. J. Physiol. 2007; 579,
729-735.
4. Xu, L., Okuda-Ashitaka, E., Matsumura, S., Mabuchi,T., Okamoto, S., Sakimura, K., Mishina, M. and Ito, S.
Signal pathways coupled to activation of neuronal
nitric oxide synthase in the spinal cord by
nociceptin/orphanin FQ. Neuropharmacology 2007; 52,
1318-1325.
5. Aiba, A., Inokuchi, K., Ishida, Y., Itohara, S.,
Kobayashi, K., Masu, M., Mishina, M., Miyakawa, T.,
Mori, H., Nakao, K., Obata, Y., Sakimura, K., Shiroishi,T., Wada, K. and Yagi, Y. Mouse liaison for integrative
brain research. Neurosci. Res. 2007; 58, 103-104.
6. Mishina, M. and Sakimura, K. Conditional genetargeting on the pure C57BL/6 genetic background.
Neurosci. Res. 58, 2007; 105-112.
7. Hasegawa, S., Yamaguchi, M., Nagao, H., Mishina, M.
and Mori, K. Enhanced cell-to-cell contacts between
activated microglia and pyramidal cell dendrites
following kainic acid-induced neurotoxicity in the
hippocampus. J. Neuroimmunol. 2007; 186, 75-85.
8. Takemoto-Kimura, S., Ishihara-Ageta, N., Nonaka, M.,
Adachi-Morishima, A., Mano, T., Okamura, M., Fujii,
H., Fuse, T., Hoshino, M., Suzuki, S., Kojima, M.,
Mishina, M., Okuno, H. and Bito, H. Regulation ofdendritogenesis via a lipid raft-associated Ca2+/
calmodulin-dependent protein kinase CLICK-III/
CaMKIγ. Neuron 2007; 54, 755-770.
9. Xu, L., Mabuchi, T., Katano, T., Matsumura, S.,
Okuda-Ashitaka, E., Sakimura, K., Mishina, M. and Ito,
S. Nitric oxide (NO) serves as a retrograde messenger
to activate neuronal NO synthase in the spinal cord via
NMDA receptors. Nitric Oxide 2007; 17, 18-24.
10. Tian, L., Stefanidakis, M., Ning, L., Lint, P. V.,
Nyman-Huttunen, H., Libert, C., Itohara, S., Mishina,
M., Rauvala, H. and Gahmberg, C. G. Activation of
NMDA receptors promotes dendritic spine
development through MMP-mediated ICAM-5
cleavage. J. Cell Biol. 2007; 178, 687-700.
11. Uemura, T., Kakizawa, S., Yamasaki, M., Sakimura, K.,
Watanabe, M., Iino, M. and Mishina, M. Regulation of
long-term depression and climbing fiber territory by
GluRδ2 at parallel fiber synapses through its carboxyl
terminal domain in cerebellar Purkinje cells. J.
Neurosci., in press.
12. Kimura, M., Taniguchi, M., Mikami, Y., Masuda, T.,
Yoshida, T., Mishina, M. and Shimizu, T. Identification

29

and characterization of zebrafish semaphoring 6D.
Biochem. Biophys. Res. Commun., in press .

32

Department of Pathology and
Diagnostic Pathology
Professor
Masashi Fukayama, M.D.,Ph.D.

Associate Professor
Noriyoshi Fukushima, M.D., Ph.D.

Lecturer
Hiroshi Uozaki, M.D., Ph.D. (Division of Diagnostic Pathology),
Satoshi Ota, M.D., Ph.D.

Lecturer (Hospital)
Kenji Kashima, M.D., Ph.D.,

Yutaka Takazawa, M.D., Ph.D.,

Toru Motoi, M.D., Ph.D. (visiting researcher, USA)

Associate
Akiteru Goto, M.D., Ph.D.,

Takashi Sakatani, M.D., Ph.D.,

Junji Shibahara, M.D., Ph.D.,

Tetsuo Ushiku, M.D., Ph.D.

Technical Support Specialist
Takamichi Natsuzaka,

Homepage

Yasuyuki Morishita,

M.T., Shinichi Harada

http://pathol.umin.ac.jp/

Introduction and Organization
In 2003, Department of Human Pathology was
united with Department of Diagnostic Pathology, andDepartment of Human Pathology and Diagnostic Pathology has been freshly started. It is responsible forthe practice of diagnostic pathology, education, andresearch in conjunction with Division of Diagnostic
Pathology of the University Hospital. Our aim is theconstruction of “pathology as clinical medicine” aswell as “next-generation pathology for translational
research”.
In 2006, Lecturer Fukushima was promoted to Associate professor, Associate Ohta to Lecturer, andHospital Lecturer Uozaki was transferred to the department lecturer. Associate Sakatani has freshly par-taken.
Seven postgraduate students finished the course andreceived Ph.D. In the new fiscal year, 2007, there are
thirteen postgraduates (including one foreign student).
The research is mainly based on morphology, targeting human diseases. On the other hand, we takecharge of General pathology course for the 1st gradestudents in collaboration with Department of Molecular Pathology, Systematic pathology, Clinical clerkship, and Bedside-learning (BSL) for the 2nd – 4th
grade students.

Clinical activities (pathologic
diagnosis and autopsy)
Together with Division of Diagnostic Pathology, we

33

are responsible for the pathologic diagnosis and autopsy in the University Hospital. Utilizing Rapid tissue processing system, which was installed in 2004,
we are setting out the technical and systematic development for rapid diagnosis (see the corresponding
section of Division of Diagnostic Pathology).
Clinico-pathological conferences (CPCs) for thetwo autopsy cases are held every month in the hospital.
Furthemore, surgical pathological conferences are
regularly held with each clinical division, and discusses the cases of various tumors, including thorax,
upper gastrointestinal tract, neurosurgery, liver, pancrea-biliary tract, urology, gynecology, mammary
gland, and orthopedics, as well as biopsy cases of liver,kidney and skin.

Teaching activities
We take on General Pathology course for the 1st
grade of undergraduate students, especially in its
morphological field. The course program and lecturenotes are available in UT Open Course Ware
(http://ocw.u-tokyo.ac.jp/).
Each class of Systematic Pathology course and theexercise is now held every week in parallel with thatof Systematic Medical course. Such integrated classes
are expected to promote the practical understanding ofsystemic pathology for students. In every half courseof the pathological exercises, handouts are delivered.
And slide-projected examinations have been conducted since 2000, which are available on our website.
Clinical clerkship for the 3rd grade, and BSL for the
4th grade are carried out. In BSL, following courses
are included; autopsy pathologic practices including
presentation of each case for paired students, surgicalpathologic practice using various tumor sections, andinspection of Hospital.
The past graduate examinations of Diagnostic Pathology are also referred on the web.

Research activities
The firsrt major theme is “chronic inflammationand neoplasms”, for which various investigations aredeveloped, including Epstein-Barr virus associatedneoplasms (gastric carcinoma), lung carcinoma andscar formation, and carcinogenesis in pulmonary fi-

brosis.
The second main theme is the search of target
molecules for cancer therapy by global analysis ofexpression profiles of various cancers, in collaboration with Research Center for Advanced Science andTechnology, the University of Tokyo.

References
1. Barua RR, Uozaki H, Chong JM, Ushiku T, Hino
R, Chang MS, Nagai H, Fukayama M. Phenotype
analysis by MUC2, MUC5AC, MUC6, and CD10
expression in Epstein-Barr virus-associated gastriccarcinoma. J Gastroenterol. 2006 Aug;41(8):733-9.
2. Chang MS, Uozaki H, Chong JM, Ushiku T, Sakuma K, Ishikawa S, Hino R, Barua RR, Iwasaki Y,
Arai K, Fujii H, Nagai H, Fukayama M. CpG island methylation status in gastric carcinoma withand without infection of Epstein-Barr virus. Clin
Cancer Res. 2006 May;12(10):2995-3002.
3. Endo H, Takemura T, Fukayama M, Tsutsumi O.
Comparison of the number of spermatogonia andSertoli cells in fetal and neonatal testes autopsied
between 1958-1964 and 1989-1998 in Tokyo. Reprod Med Biol 2006 Mar;5(1):65-70.
4. Hanajiri K, Maruyama T, Kaneko Y, Mitsui H,
Watanabe S, Sata M, Nagai R, Kashima T, Shibahara J, Omata M, Matsumoto Y. Microbubble-induced increase in ablation of liver tumors byhigh-intensity focused ultrasound. Hepatol Res.
2006 Dec;36(4):308-14.
5. Hara T, Kawahara N, Tsuboi K, Shibahara J,
Ushiku T, Kirino T. Sarcomatous transformationof clival chordoma after charged-particle radiotherapy. Report of two cases. J Neurosurg. 2006
Jul;105(1):136-41.
6. Hishinuma M, Ohashi KI, Yamauchi N, Kashima
T, Uozaki H, Ota S, Kodama T, Aburatani H, Fukayama M. Hepatocellular oncofetal protein,glypican 3 is a sensitive marker for alphafetoprotein-producing gastric carcinoma. Histopathology. 2006 Nov;49(5):479-86.
7. Ishizawa T, Komori T, Shibahara J, Ishizawa K,
Adachi J, Nishikawa R, Matsutani M, Hirose T.
Papillary glioneuronal tumor with minigemistocytic components and increased proliferative ac-

34tivity. Hum Pathol. 2006 May;37(5):627-30.
8. Ito H, Funahashi S, Yamauchi N, Shibahara J,
Midorikawa Y, Kawai S, Kinoshita Y, Watanabe A,
Hippo Y, Ohtomo T, Iwanari H, Nakajima A, Makuuchi M, Fukayama M, Hirata Y, Hamakubo T,
Kodama T, Tsuchiya M, Aburatani H. Identification of ROBO1 as a novel hepatocellular carcinoma antigen and a potential therapeutic and diagnostic target. Clin Cancer Res. 2006 Jun 1;12(11Pt 1):3257-64.
9. Katoh H, Shibata T, Kokubu A, Ojima H, Fukayama M, Kanai Y, Hirohashi S. Epigenetic instability and chromosomal instability in hepatocellular carcinoma. Am J Pathol. 2006 Apr;168(4):1375-84.
10. Kawamura-Saito M, Yamazaki Y, Kaneko K, Kawaguchi N, Kanda H, Mukai H, Gotoh T, Motoi T,
Fukayama M, Aburatani H, Takizawa T, Nakamura
T. Fusion between CIC and DUX4 up-regulates
PEA3 family genes in Ewing-like sarcomas witht(4;19)(q35;q13) translocation. Hum Mol Genet.
2006 Jul 1;15(13):2125-37.
11. Konishi T, Watanabe T, Shibahara J, Nagawa H.
Surveillance colonoscopy should be conducted inpatients with colorectal Shistosomiasis even after
successful treatment of the disease. Int J Immunopathol Pharmacol. 2006 Jan-Mar;19(1):245-6.
12. Maeda E, Uozumi K, Kato N, Akahane M, Inoh S,
Inoue Y, Beck Y, Goto A, Makuuchi M, Ohtomo K.
Magnetic resonance findings of bile duct adenoma
with calcification. Radiat Med. 2006 Jul;24(6):459-62.
13. Matsui Y, Sugawara Y, Tsukada K, Kishi Y, Shibahara J, Makuuchi M. Aspergillus thyroiditis in aliving donor liver transplant recipient. J Infect.
2006 Dec;53(6):e231-3.
14. Mitsui J, Saito Y, Momose T, Shimizu J, Arai N,
Shibahara J, Ugawa Y, Kanazawa I, Tsuji S, Murayama S. Pathology of the sympathetic nervous
system corresponding to the decreased cardiac uptake in 123I-metaiodobenzylguanidine (MIBG)
scintigraphy in a patient with Parkinson disease. J
Neurol Sci. 2006 Apr 15;243(1-2):101-4.
15. Morikawa T, Nagata M, Tomita K, Kitamura T,
Goto A, Chong JM, Fukayama M. Phyllodes tumor of the prostate with exuberant glandular hy-

perplasia. Pathol Int. 2006 Mar;56(3):158-61.
16. Nakao K, Mochiki M, Nibu K, Sugasawa M, Uozaki H. Analysis of prognostic factors of nasopharyngeal carcinoma: impact of in situ hybridization for Epstein-Barr virus encoded small RNA 1.
Otolaryngol Head Neck Surg. 2006 Apr;134(4):639-45.
17. Narahashi T, Niki T, Wang T, Goto A, Matsubara
D, Funata N, Fukayama M. Cytoplasmic localization of p63 is associated with poor patient survivalin lung adenocarcinoma. Histopathology. 2006
Oct;49(4):349-57.
18. Nozaki K, Nomura S, Shimizu N, Hiki N, Yoshizawa N, Aikou S, Kubota K, Yamaguchi H, Kurosaka H, Shinozaki A, Mafune K, Fukayama M,
Kaminishi M. Helicobacter pylori-negative /API2-MALT1 translocation-negative low-grade
MALT lymphoma. Gastric Cancer. 2006;9(3):229-34.
19. Okada T, Sasaki F, Cho K, Itoh T, Ota S, Todo S.
Histological differentiation between prenatallydiagnosed choledochal cyst and type I cystic biliary atresia using liver biopsy specimens. Eur J
Pediatr Surg. 2006 Feb;16(1):28-33.
20. Okada T, Sasaki F, Takahashi H, Taguchi K, Takahashi M, Watanabe K, Itoh T, Ota S, Todo S.
Management of childhood and adolescent thyroid
carcinoma: long-term follow-up and clinical characteristics. Eur J Pediatr Surg. 2006 Feb;16(1):8-13.
21. Ota S, Hishinuma M, Yamauchi N, Goto A, Morikawa T, Fujimura T, Kitamura T, Kodama T, Aburatani H, Fukayama M. Oncofetal protein glypican-3 in testicular germ-cell tumor. Virchows Arch.
2006 Sep;449(3):308-14.
22. Rogers CD, Fukushima N, Sato N, Shi C, Prasad
N, Hustinx SR, Matsubayashi H, Canto M, Eshleman JR, Hruban RH, Goggins M. Differentiating
Pancreatic Lesions by Microarray and QPCR
Analysis of Pancreatic Juice RNAs. Cancer Biol
Ther. 2006 Oct;5(10):1383-9.
23. Sato N, Fukushima N, Matsubayashi H, Iacobuzio-Donahue CA, Yeo CJ, Goggins M. Aberrant
methylation of Reprimo correlates with genetic
instability and predicts poor prognosis in pancreatic ductal adenocarcinoma. Cancer. 2006 Jul;
107(2):251-7.

35

24. Sato N, Fukushima N, Chang R, Matsubayashi H,
Goggins M. Differential and epigenetic gene expression profiling identifies frequent disruption of
the RELN pathway in pancreatic cancers. Gastroenterology. 2006 Feb;130(2):548-565.
25. Shibahara J, Kashima T, Kikuchi Y, Kunita A,
Fukayama M. Podoplanin is expressed in subsets
of tumors of the central nervous system. VirchowsArch. 2006 Apr;448(4):493-9.
26. Takeuchi K, Tanaka-Taya K, Kazuyama Y, Ito
YM, Hashimoto S, Fukayama M, MoriS. Prevalence of Epstein-Barr virus in Japan: trends andfuture prediction. Pathol Int. 2006 Mar;56(3):112-6.
27. Tsurumaki Y, Tomita K, Kume H, Yamaguchi T,
Morikawa T, Takahashi S, Takeuchi T, Kitamura T.
Predictors of seminal vesicle invasion before
radical prostatectomy. Int J Urol. 2006 Dec;13(12):1501-8.
28. Yamada Y, Fujimura T, Takahashi S, Takeuchi T,
Takazawa Y, Kitamura T. Tubulovillous adenoma
developing after urinary reconstruction using ileal
segments. Int J Urol. 2006 Aug;13(8):1134-5.
29. Yamaguchi U, Hasegawa T, Sakurai S, Sakuma Y,
Takazawa Y, Hishima T, Mitsuhashi T, Sekine S,
Chuman H, Shimoda T. Interobserver variability inhistologic recognition, interpretation of KIT immunostaining, and determining MIB-1 labelingindices in gastrointestinal stromal tumors andother spindle cell tumors of the gastrointestinal
tract. Appl Immunohistochem Mol Morphol. 2006
Mar;14(1):46-51.
30. Zhang SC, Hironaka S, Ohtsu A, Yoshida S,
Hasebe T, Fukayama M, Ochiai A. Computerassisted analysis of biopsy specimen microvessels
predicts the outcome of esophageal cancers treatedwith chemoradiotherapy. Clin Cancer Res. 2006
Mar 15;12(6):1735-42.

36

Department of MolecularPathology
Professor
Kohei Miyazono, M.D., D.M.S.

Associate Professor
Keiji Miyazawa, Ph.D.

Associate
Masao Saitoh, D.D.S.,

Homepage

Tetsuro Watabe, Ph.D.

http://beta-lab.umin.ac.jp/

Introduction and Organization
Our department has a more than 100-year history
from its establishment as the Department of Pathology.
Prof. Miyazono started to work as the professor of the
Department of Molecular Pathology in August 2000.
Now, the Department consists of a professor, an associate professor, two associates, 4 technicians, andseveral research fellows, including 6 graduate students,
5 master course students, 2 post-doctoral fellows, anda research fellow from France.

Teaching activities
Our department takes responsibility for lectures on“General Pathology” for the undergraduate students of
the Faculty of Medicine in collaboration with the staffof the Department of Human Pathology. Teaching responsibilities include lectures on General Pathology
related to the mechanisms of diseases. Since we believe it very important for medical students to study
Basic Oncology, we spend some time for lectures on aseries of basic tumor biology in our lectures. In addition, we offer several laboratory courses for students
from molecular pathological points of view.
We also supervise research activities of the graduate
students of the Department. Our laboratory is locatedat the 11th floor at the Research Building of Graduate

School of Medicine. The laboratory is very convenientfor doing research, since most of the experiments canbe done at this floor. We have “Progress Meeting”
twice a month, “Journal Club” every Friday, and“Monday Seminar” once a month in collaboration
with the Department of Biochemistry at the Cancer
Institute of the Japanese Foundation for Cancer Research.
We have been doing collaboration with the Ludwig
Institute for Cancer Research, Uppsala, Sweden for
more than 10 years. We have annual TGF-β meetingin Sweden every spring, and some graduate students
participate in the meeting and orally present their results.
Graduate students also present data at various meetings, including Annual Meetings of the JapaneseCancer Association, and Annual Meeting of the Molecular Biology Society of Japan. At the corridor of
our laboratory, posters of our graduate students reported at these meetings are presented.

Research activities
Our major research interest is to elucidate how
members of the TGF (transforming growth factor)-βfamily transduce signals, and how they regulate
growth, differentiation, and apoptosis of various cells.
We are also interested in the regulation of angiogene-37

sis and lymphangiogenesis using embryonic stem (ES)cell-derived vascular progenitor cells and other endothelial cells.
In order to elucidate the effectiveness of TGF-β inhibitors in vivo, we have treated nude mice subcutaneously inoculated with human pancreatic adenocarcinoma cell lines BxPC3, Panc-1, and MiaPaca-2 by asmall molecule TGF-β inhibitor (LY364947) and astealth nanovector, a polymeric micelle made ofadriamycin (ADR) bound to polyethylene glycol(PEG)-poly(asparatic acid) block copolymer (micelleADR). Micelle-ADR alone suppressed the growth ofpancreatic cells in vivo, but a combination of
LY364947 and micelle-ADR more potently suppressed their growth. Systemic administration of
TGF-β inhibitors is expected to inhibit tissue fibrosis,
stimulate immune function, and alter the process ofangiogenesis. We have found that because of the lossof attachment of pericytes to endothelial cells,
LY364947 made the tumor vessels more leaky thancontrol, leading to efficient delivery of micelle-ADR
to tumor tissues. Combined treatment with TGF-βinhibitor and micelle-ADR also potently inhibited
growth of diffuse type gastric carcinoma in an orthotopic transplantation model using OCUM-2MLN
cells.
Lymphatic systems play important roles not only inphysiological condition but also in pathological processes such as cancer metastasis. However, molecularmechanisms that govern lymphangiogenesis remain
largely unknown. Vascular endothelial growth factor
receptor 3 (VEGFR-3) and a homeobox transcription
factor Prox1 are expressed in lymphatic endothelial
cells (LEC). Prox1 is essential for lymphangiogenesis
because the sprouting of LEC from blood vessels isarrested in Prox1-null embryos. We thus studied how
Prox1 modulates behavior of mouse ESC-derived endothelial cells and human umbilical vein endothelial
cells (HUVECs). We showed that via induction of
integrin α9 expression, Prox1 inhibits sheet formationand stimulates motility of endothelial cells. Prox1expressing blood vascular endothelial cells (BECs)
preferentially migrated toward VEGF-C throughup-regulation of the expression of integrin α9 and
VEGFR3. In mouse embryos, expression of VEGFR3
and integrin α9 is increased in Prox1-expressing LECs
compared to BECs. Silencing the expression of Prox1

in human LECs resulted in decrease in the expressionof integrin α9 and VEGFR3, leading to the decreased
chemotaxes toward VEGF-C. Our findings suggested
that Prox1 plays important roles in conferring andmaintaining the characteristics of LECs by modulating
multiple signaling cascades, and that VEGFR3 andintegrin α9 may function as key regulators of lymphangiogenesis acting downstream of Prox1.

References
1. Fukuda, N., Saitoh, M., Kobayashi, N., andMiyazono, K. (2006) Execution of BMP-4induced apoptosis by p53-dependent ER dysfunction in myeloma and B-cell hybridoma cells.
Oncogene 25 (25), 3509-3517.
2. Shirakawa, K., Maeda, S., Gotoh, T., Hayashi, M.,
Shinomiya, K., Ehata, S., Nishimura, R., Mori, M.,
Onozaki, K., Hayashi, H., Uematsu, S., Akira, S.,
Ogata, E., Miyazono, K., and Imamura, T. (2006)
CCAAT/enhancer-binding protein homologous
protein (CHOP) regulates osteoblast differentiation. Mol. Cell. Biol. 26 (16): 6105-6116.
3. Nagata, M., Goto, K., Ehata, S., Kobayashi, N.,
Saitoh, M., Miyoshi, H., Imamura, T., Miyazawa,K., and Miyazono, K. (2006) Nuclear and cytoplasmic c-Ski differentially modulate cellularfunctions. Genes Cells 11 (11), 1267-1280.
4. Miyazono, K., Ishikawa, F., Winterhager, E.,
Deppert, W., and Rajewsky, M.F. (2006) TenthJapanese-German workshop on molecular andcellular aspects of carcinogenesis, Essen, Germany, 29 September-1 October 2005. Cancer Sci.
97 (4), 332-339.
5. Watabe, T., Yamashita, J.K., Mishima, K., andMiyazono, K. (2006) TGF-β signaling in embryonic stem cell-derived endothelial cells. Methods
Mol. Biol. 330: 341-351.
6. Miyazono, K., Maeda, S., and Imamura, T. (2006)
Smad transcriptional co-activators and corepressors. In: Smad Signaling (ten Dijke, P. andHeldin, C.-H. eds.) Springer, pp. 277-293.

40

Department of Microbiology
Professor
Akio Nomoto, Ph.D.

Assistant Professor
Seii Ohka, Ph.D.,

Tsubasa Munakata, Ph.D.,

Nobuhiko Kamoshita, M.D., Ph.D.

Homepage

http://microbiology.m.u-tokyo.ac.jp/

Introduction and Organization
Microbial disease has been recognized as the major
threat to human health throughout the history. Despite
the development of preventive and therapeutic interventions against some pathogenic microbes, infectious
disease is still one of the most significant medical
problems. On the other hand, microbial organisms
have served as a useful model as well for elucidating
the molecular mechanisms of a variety of biologicalevents, providing useful insights into life science. Recently, efforts have also been initiated by a number of
research groups to utilize animal viruses as a tool forhuman gene therapy. In order to familiarize students
with these issues, importance of microbiology inmedical education is increasing more rapidly than ever.
To fulfill this requirement, our department, as the only
basic microbiology unit in the Faculty, currently assumes a responsibility for teaching bacteriology, mycology, and virology to medical undergraduates.

Education
Undergraduate Course, Faculty of Medicine
In a series of lectures (totally 64 hr) and laboratory
courses (36 hr), the following subjects are covered.
1) Molecular biology of bacteria, phages, and animalviruses2) Mechanisms of microbial diseases
3) Laboratory diagnosis of pathogenic microbes
4) Infection control and biosafety
5) Application of microbial organisms for biotech-

nology6) Socioeconomic impact of microbial diseases
In addition to the staff of our department, experts
from the National Institute of Infectious Diseases (Dr.
Watanabe and Dr. Yoshikura), Faculty of Agriculture(Dr. Onodera), and Institute of Medical Science (Dr.
Sasakawa, Dr. Kawaoka, Dr. Iwamoto, Dr. Saito, andDr. Matano) contribute to the teaching activities.

Research
1. IRES (internal ribosome entry site)-dependenttranslation and virus tropism
Ohka, S., Kamoshita, N., Munakata, T., andNomoto, A.
2. Poliovirus entry via PVR (poliovirus receptor)
Ohka, S., and Nomoto, A.
3. Effect of viral infection on cell metabolism
Kamoshita, N., Matsuda, N., Ohka, S., andNomoto, A.
4. Blood brain barrier permeation of poliovirus
Mikame, M., Ohka, S., and Nomoto, A.
5. Oral infection mechanism of poliovirus
Ohka, S., Kajiro, K., and Nomoto, A.
6. Biochemical analysis of HCV (hepatitis C
virus) genome as an RNA replicon
Okamoto, Y., Munakata, T., Kamoshita, N., andNomoto, A.
7. Molecular basis for HCV pathogenesis
Munakata, T., Hayase, N., and Nomoto, A.
8. Development of novel inhibitors of HCV
replication

41

Munakata, T., Inada, M., and Nomoto, A.

Publications
1. Fujiyuki T, Ohka S, Takeuchi H, Ono M, Nomoto
A, Kubo T. Prevalence and phylogeny of Kakugo
virus, a novel insect picorna-like virus that infects
the honeybee (Apis mellifera L.), under various
colony conditions. J Virol. 2006;80:11528-38.

42

Department of Infection Control
and Prevention
Professor
Kazuhiko Koike, M.D., Ph.D.

Lecturer
Kyoji Moriya, M.D., Ph.D.
Hiroshi Yotsuyanagi, M.D., Ph.D.

Associate
Yoshizumi Shintani, M.D.,

Homepage

Shu Okugawa, M.D., Ph.D.

http://www.cc.h.u-tokyo.ac.jp/mulins/kansen/index.html(inside the hospital only)

Introduction and Organization
The Department of Infection Control and Prevention started at first as the Division of Hospital Infection Control Services on January 23, 1991. This division developed into the Division of Infection Control
and Prevention on September l, 1993 and the present
department on June 4, 1994. Currently, our faculty
consists of one professor, two lecturers, 6 guest lecturers, two associates, one research student, 12 laboratory technicians, and two office assistants. For isolation and identification of microorganisms fromclinical specimens, we amalgamated the microbiology
unit from the Department of Clinical Laboratory in
2001.

Clinical activities
Our daily activities are as follows:
1) Surveillance and control of hospital-acquired infection, such as infection or colonization of methicillin-resistant Staphylococcus aureus and otherdrug-resistant microbes.
2) Investigation of trends in weekly bases andmonthly reports to all departments; Screening ofcolonization; monitoring of appropriate use of an-tibiotics such as mupirocin and vancomycin.
3) Microbiological investigation of wards and environment (at request or need).
4) Detection, investigation, intervention and controlof the hospital infection outbreak.
5) Offering of information and advice on
HIV-infected patients’ management.
6) Direct inquiries and advises on management ofpatients with various infections through ward
rounds every week.

Teaching activities
We have been charged for education of undergraduate students on the course of medicine (lectures andpractical exercises on the infection control for the 3rd
and 4th grade students and lectures on infectious diseases for the 4th grade students), the course of healthscience (lectures on microbiology), and the school ofnursing (lectures and practical exercises on microbiology). These lectures and exercises contain subjects
not only on the hospital infection but also on clinicalmicrobiology. We are also engaged in the education of
graduate students as well as hospital staff.
For postgraduate education, we have been committed to the guidance for new postgraduates and resi-

43

dents on the hospital and occupational infection control. We have been also offering our information andtechnique on occasions of request.

Research activities
We have been mainly studying on following subjects:
1) Development of preemptive strategies for the control of healthcare-associated infection2) Development of new methods in infection control
and treatment of viral hepatitis
3) Molecular pathogenesis of hepatocellular carcinoma in HCV infection4) Pathogenesis of progression of HIV infection5) Molecular pathogenesis of the mitochondrial
disturbances in viral infections
6) Molecular pathogenesis of hepatitis B viral infection7) Host defences to microorganisms
8) Molecular analysis of innate immunity in microorganism infection
9) New detection method and pathogenesis of opportunistic cytomegaloviral infection10) Mechanism of multi-drug resistant microorganisms

References
1) Koike K. Hepatitis C virus infection presenting
with metabolic disease by inducing insulin resistance. Intervirology 2006;49:51-57.
2) Koike K, Miyoshi H. Oxidative stress and hepatitis C viral infection. Hepatol Res 2006;34:65-76.
3) Nukui Y, Tajima S, Kotaki A, Ito M, Takasaki T,
Koike K, Kurane I. Novel dengue virus type 1
from travelers to Yap State, Micronesia. Emerg
Infect Dis 2006;12: 343-346.
4) Koike K. Oxidative stress and apoptosis in hepatitis C: the core issue. J Gastroenterology 2006;41:
292-294.
5) Okuse C, Yotsuyanagi H, Nagase Y, Kobayashi Y,
Yasuda Y, Koike K, Iino S, Suzuki M, Itoh F. Risk
Factors for Retinopathy Associated with Interferon Alpha-2b and Ribavirin Combination Therapy in Patients with Chronic Hepatitis C. World J
Gastroenterol 2006;12:3759-3759.

6) Matsuoka-Aizawa S, Gatanaga H, Sato H, Koike
K, Kimura K, Oka S. Gag substitutions responsible for nelfinavir-dependent enhancement of precursor cleavage and human immunodeficiency
virus type-1 replication. Antiviral Res 2006;70:
51-59.
7) Saito R, Sato K, Kumita W, Inami N, Nishiyama
H, Okamura N, Moriya K, Koike K. Role of type
II topoisomerase mutations and AcrAB efflux
pump in fluoroquinolone-resistant clinical isolatesof Proteus mirabilis. J Antimicrob Chemoth 2006;
58:673-677.
8) Okugawa S, Yanagimoto S, Tsukada K, Kitazawa
T, Koike K, Kimura S, Nagase H, Hirai K, Ota Y.
Bacterial fragelin inhibits T cell receptormediated activation of T cells by inducing suppressor of cytokine signaling-1 (SOCS-1). Cell
Microbiol 2006;8:1571-1580.
9) Kitazawa T, Ota Y, Kada N, Morisawa Y, Yoshida
A, Koike K, Kimura S. Successful vancomycin
desensitization with a combination of rapid andslow infusion methods. Intern Med 2006;45:
317-321.
10) Koike K. Antiviral treatment of hepatitis C: present status and future prospects. J Infect Chemother 2006;12:227-232.
11) Takahashi H, Yotsuyanagi H, Yasuda K, Koibuchi
T, Suzuki M, Kato T, Nakamura T, Iwamoto A,
Nishioka K, Iino S, Koike K, Itoh F. Molecularepidemiology of hepatitis A virus in metropolitan
areas in Japan. J Gastroenterol 2006;41:981-986.
12) Shin N, Sugawara Y, Tsukada K, Tamura S,
Akamatsu N, Okugawa S, Koike K, Kikuchi K,
Makuuchi M. Successful treatment of disseminated Nocardia farcinica infection in a living
donor liver transplantation recipient. Transpl
Infect Dis 2006 ;8:222-225.
13) Okuse C, Adachi K, Katakura Y, Matsunaga K,
Ishii T, Matsumoto N, Yotsuyanagi H, Iino S,
Suzuki M, Itoh F. A case of deep venous thrombosis associated with pegylated interferon alpha2b
plus ribavirin treatment of chronic hepatitis C. J
Gastroenterol. 2006;41:1231-1236.
14) Sugauchi F, Orito E, Ohno T, Tanaka Y, Ozasa A,
Kang JH, Toyoda J, Kuramitsu T, Suzuki K,
Tanaka E, Akahane Y, Ichida T, Izumi N, Inoue K,
Hoshino H, Iino S, Yotsuyanagi H, Kakumu S,

44

Tomita E, Okanoue T, Nishiguchi S, Murawaki Y,
Hino K, Onji M, Yatsuhashi H, Sata M,
Miyakawa Y, Ueda R, Mizokami M. Spatial andchronological differences in hepatitis B virus
genotypes from patients with acute hepatitis B in
Japan. Hepatol Res. 2006;36:107-114.
15) Yamada N, Okuse C, Nomoto M, Orita M,
Katakura Y, Ishii T, Shinmyo T, Osada H, Maeda
I, Yotsuyanagi H, Suzuki M, Itoh F. Obstructive
jaundice caused by secondary pancreatic tumor
from malignant solitary fibrous tumor of pleura: acase report. World J Gastroenterol. 2006;12:4922-4926.
16) Okuse C, Yotsuyanagi H, Yamada N, Ikeda H,
Takahashi H, Suzuki M, Kondo S, Kimura K,
Koike J, Itoh F. Successful treatment of hepatitis
B virus-associated membranous nephropathy withlamivudine. Clin Nephrol. 2006;65:53-56.
17) Tanaka E, Matsumoto A, Suzuki F, Kobayashi M,
Mizokami M, Tanaka Y, Okanoue T, Minami M,
Chayama K, Imamura M, Yatsuhashi H, Nagaoka
S, Yotsuyanagi H, Kawata S, Kimura T, Maki N,
Iino S, Kiyosawa K; HBV Core-Related Antigen
Study Group. Measurement of hepatitis B virus
core-related antigen is valuable for identifying patients who are at low risk of lamivudine resistance.
Liver Int. 2006;26:90-96.
18) Ikeda H, Suzuki M, Takahashi H, Kobayashi M,
Okuse N, Moriya H, Koike J, Maeyama S,
Yotsuyanagi H, Itoh F. Hepatocellular carcinoma
with silent and cirrhotic non-alcoholic steatohepatitis, accompanying ectopic liver tissue attached togallbladder. Pathol Int. 2006;56:40-45.
19) Ogata K, Ide T, Kumashiro R, Kumada H,
Yotsuyanagi H, Okita K, Akahane Y, Kaneko S,
Tsubouchi H, Tanaka E, Moriwaki H, Nishiguchi
S, Kakumu S, Mizokami M, Iino S, Sata M. Timing of interferon therapy and sources of infection
in patients with acute hepatitis C. Hepatol Res.
2006;34:35-40.
20) Koike K, Tsukada K, Yotsuyanagi H, Moriya K,
Kikuchi Y, Oka S, Kimura S. Prevalence of Coinfection with Human Immunodeficiency Virus andHepatitis C Virus in Japan. Hepatol Res 2007;37:
2-5.
21) Bi X, Gatanaga H, Koike K, Kimura S, Oka S.
Reversal periods and patterns from drug resistant

to wild-type HIV-1 after cessation of anti-HIV
therapy. AIDS Res Hum Retro 2007;23:43-50.
22) Miyamoto H, Moriishi K, Moriya K, Murata S,
Tanaka K, Suzuki T, Miyamura T, Koike K,
Matsuura Y. Hepatitis C Virus Core Protein
Induces Insulin Resistance through a PA28γDependent Pathway. J Virol 2007;81:1727-1735.
23) Moriishi K, Mochizuki R, Moriya K, Miyamoto H,
Mori Y, Abe T, Murata S, Tanaka K, Suzuki T,
Miyamura T, Koike K, Matsuura Y. Critical role of
PA28 γ in hepatitis C virus-associated steatogenesis and hepatocarcinogenesis. Proc Natl Acad
Sci USA 2007;104:1661-1666.
24) Ishizaka N, Saito K, Furuta K, Matsuzaki G, Koike K, Noiri E, Nagai R. Angiotensin II-induced
regulation of the expression and localization ofiron metabolism-related genes in the rat kidney.
Hypertens Res 2007;30:195-202.
25) Suzuki Y, Yotsuyanagi H, Okuse C, Nagase Y,
Takahashi H, Moriya K, Suzuki M, Koike K, Iino
S, Itoh F. Fatal liver failure caused by reactivationof lamivudine-resistant hepatitis B virus: A casereport. World J Gastroenterol 2007;13:964-969.
26) Hatakeyama S, Sugaya N, Ito M, Yamazaki M,
Ichikawa M, Kimura K, Kiso M, Shimizu H, Kawakami C, Koike K, Mitamura K, Kawaoka Y.
Emergence of Influenza B Viruses With Reduced
Sensitivity to Neuraminidase Inhibitors. JAMA
2007;297:1435-1442.
27) Saito R, Kumita W, Sato K, Chida T, Okamura N,
Moriya K, Koike K. Detection of plasmidmediated quinolone resistance associated with
qnrA in an Escherichia coli clinical isolate producing CTX-M-9 beta-lactamase in Japan. Int J
Antimicrob Agents 2007;29:600-602.
28) Ishizaka N, Ishizaka Y, Toda EI, Nagai R, Koike
K, Hashimoto H, Yamakado M. Relationship between smoking, white blood cell count and metabolic syndrome in Japanese women. Diabetes Res
Clin Pract 2007 Mar 10; [Epub ahead of print]29) Kitazawa T, Nakayama K, Okugawa S, Koike K,
Shibasaki Y, Ota Y. Biphasic regulation oflevofloxacin on lipopolysaccharide-induced IL1beta production. Life Sci 2007;80:1572-1577.
30) Okugawa S, Ota Y, Tatsuno K, Tsukada K,
Kishino S, Koike K. A case of invasive central
nervous system aspergillosis treated with

45

micafungin with monitoring of micafunginconcentrations in the cerebrospinal fluid. Scand J
Infect Dis 2007;39:344-346.
31) Takahashi H, Suzuki M, Ikeda H, Kobayashi M,
Sase S, Yotsuyanagi H, Maeyama S, Iino S, Itoh F.
Evaluation of Quantitative Portal Venous, Hepatic
Arterial, and Total Hepatic Tissue Blood Flow
Using Xenon CT in Alcoholic Liver Cirrhosis:
Comparison With Liver Cirrhosis C. Alcohol Clin
Exp Res 2007;31:S43-S48.
32) Koike K. Pathogenesis of HCV-associated HCC:
dual-pass carcinogenesis through the activation ofoxidative stress and intracellular signaling. Hepatol Res 2007 in press.
33) Yotsuyanagi H, Koike K. Mechanisms underlying
drug resistance in antiviral treatment for infections with hepatitis B and C viruses. J Gastroenterol 2007 in press.
34) Saito R, Sato K, Kumita W, Inami N, Nishiyama
H, Okamura N, Moriya K, Koike K. Detection ofplasmid-mediated quinolone resistance associatedwith qnrA in Escherichia coli clinical isolate producing CTX-M-9 beta-lactamase in Japan. Int J
Antimicrob Agents 2007 in press.
35) Aono J, Yotsuyanagi H, Miyoshi H, Tsutsumi T,
Fujie H, Shintani Y, Moriya K, Okuse C, Suzuki
M, Yasuda K, Iino S, Koike K. Amino acid substitutions in S region of hepatitis B virus in thesera from patients with acute hepatitis. Hepatol
Res 2007 in press.
36) Ichibangase T, Moriya K, Koike K, Imai K. A
novel proteomics method revealed disease-related
proteins in the liver of hepatitis C mouse model. J
Proteome Res 2007 in press.

48

Department of Immunology
Professor
Tadatsugu Taniguchi,Ph.D.

Lecturer
Akinori Takaoka, M.D., Ph.D.

Associate
Kenya Honda, M.D., Ph.D.,

Homepage

Hideyuki Yanai, Ph.D.

http://www.m.u-tokyo.ac.jp/mcm/

Introduction and Organization
The Department of Immunology was formerly
called the Department of Serology, which has a history going back to 1918. The department was changed
to its present name, when Dr. Tomio Tada, now Professor Emeritus of The University of Tokyo, took his
position in 1977 as the professor and chair of the department. Dr. Tada has made great contributions thatmade this department world-renowned, through hisinnovative research as well as his great contributions
to the international community of immunologists. After his retirement in 1994, we basically followed the
tradition of the department established by Dr. Tada
and tried to improve it further, in terms of providing
high-standard education to students and cutting-edge
research in immunology worldwide. Research projects
currently being conducted began with the originalidentification of two cytokine genes and their characterization between the late 1970s and the early 1980s,
namely, the genes encoding human fibroblast interferon (now known as IFN- ) and interleukin-2 (IL-2).
These initial studies have led us to further characterization of these cytokine systems in the context of theregulation of immunity and oncogenesis. One of ourmajor contributions is the discovery and characterization of a new family of transcription factors, termedinterferon regulatory factors (IRFs). Our current research interests are aimed at clarifying the function
and regulation of the IRF family of transcription factors in oncogenesis and immunity. As a part of ourscientific and educational activities, we organize many
seminars by inviting distinguished scientists from allover the world..

Teaching activities
Our teaching responsibility is to provide lectures on
immunobiology, immunochemistry and molecularimmunology to the undergraduate students of the faculty. It is also our responsibility to provide laboratory
courses on basic immunology to students. In addition
to lectures and laboratory courses provided by ourown staff members, special lectures are also given byguest experts. We also offer a special training course(called ‘free quarter’) of basic and advanced biological and immunological techniques to medical students.
The education of graduate students is based on weekly
conferences during which the students present the
progress of their own research projects and discuss ontheir future directions. Lectures on leading research
activities are given by active researchers from overseas whenever they visit our department. The students
may gain a profound interest in the field through theselectures.

Research activities
Our research field includes cellular and molecularimmunology in general. Once an immune response isinitiated by an antigenic stimulus, the magnitude of
the response is controlled by the complex mechanisms.

49

We have been extensively analyzing mechanisms thatfunction in the regulation of gene expression and signal transduction in host defense systems. In particular,
we focus on the molecular mechanisms underlying
host defense against viral and bacterial infections.
Among these mechanisms, the interferon (IFN) system is the most powerful and important for the controlof such infections. During the course of the study, we
have identified the interferon regulatory factor (IRF)
family, which play critical roles in immunity. Most
notably, studies of IRFs have revealed their remarkable functional diversity in regulating the immune
systems, in particular, as the key regulators of the
TLR-induced immune response. We showed that thetranscription factor IRF-7 is essential for both the virus-activated MyD88-independent pathway as well as
the TLR-activated MyD88-dependent pathway of
IFN- / gene induction. We recently found that RF-5
is essential for the MyD88-dependent gene induction
program, which is commonly activated by TLRs.
IRF-5 interacts with and is activated by MyD88 and
TRAF6, and that TLR activation results in the nuclear
translocation of IRF-5 to activate cytokine gene transcription.
Host defense consists of two main aspects, namely,
immune response to invading pathogens and suppression of tumor development. Using IRF5 gene-targeted
mice (Irf5-/- mice), we discovered a new facet of the
IRF5 function in the regulation of immune response
and tumor suppression. We found that IRF5 is criticalfor antiviral immunity, by showing that Irf5-/- mice arevulnerable to virus infections and the mutant fibroblasts are resistant to apoptosis upon viral infection,
resulting in an enhanced viral propagation. We also
provided evidence that IRF5 is critical for the induction of apoptosis, but not in cell cycle arrest, in response to DNA damage and that IRF5 functions as atumor suppressor by acting on a pathway that may be
distinct from that for p53. These results provide a newlink in the transcriptional network underlying antiviral
immunity and tumor suppression.
In addition, we also reported the presence of distinct pathways of the p53-dependent apoptosis, mediated by Noxa and Puma.

References
1. Honda, K. and Taniguchi, T.; IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. (2006). Nature Rev. Immunol., 6, 644-659.
2. Honda, K., Takaoka, A., and Taniguchi, T.; Type I
interferon gene induction by the interferon regulatory factor family of transcription factors.
(2006). Immunity, 25(3):349-60.
3. Negishi, H., Fujita, Y., Yanai, H., Sakaguchi, S.,
Ouyang, X., Shinohara, M., Takayanagi, H., Ohba,
Y., Taniguchi, T., and Honda, K.; Evidence for licensing of IFN-γ-induced IFN regulatory factor
1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program. (2006).
Proc. Natl. Acad. Sci. U S A., 103, 15136-15141.
4. Shibue, T. and Taniguchi T.; BH3-only proteins:
Integrated control point of apoptosis. (2006). Int. J.
Cancer, 119, 2036-2043.
5. Shibue, T., Suzuki, S., Okamoto, H., Yoshida, H.,
Ohba, Y., Takaoka, A., and Taniguchi, T.; Differential contribution of Puma and Noxa in dual
regulation of p53-dependent apoptotic pathways.
(2006). EMBO J, 25, 4952-4962.
6. Ouyang, X., Negishi, H., Takeda, R., Fujita, Y.,
Taniguchi, T. and Honda, K.; Cooperation between MyD88 and TRIF pathways in TLR synergy via IRF5 activation. (2007). Bioch. Biophy.
Res. Comm., 354, 1045-1051.
7. Yanai, H., Chen, H., Inuzuka, T., Kondo, S., Mak,
W. T., Takaoka. A., Honda, K. and Taniguchi, T.;
Role of IFN regulatory factor 5 transcription factor in antiviral immunity and tumor suppression.
(2007). Proc. Natl. Acad. Sci. U S A., 104,
3402-3407.
8. Onoguchi, K., Yoneyama, M., Takemura, A.,
Akira, S., Taniguchi, T., Namiki, H., and Fujita T.;
Viral Infections Activate Types I and III Interferon
Genes through a Common Mechanism. (2007). J.
Biol. Chem. 282(10), 7576-7581.

52

Department of Radiology
Professor
Kuni Ohtomo, M.D.,Ph.D.

Associate Professor
Toshimitsu Momose, M.D.,Ph.D.,

Shigeki Aoki, M.D.,Ph.D.,

Keiichi Nakagawa, M.D.,Ph.D.

Lecturer
Atsurou Terahara M.D.,Ph.D,

Osamu Abe, M.D.,Ph.D.,

Masaaki Akahane, M.D.,

Yoshitaka Masutani, Ph.D.,

Tomohiko Masumoto, M.D.,Ph.D

Assisstant Professor
Syuhei Komatsu, M.D.,

Shinichi Inoh, M.D.,

Harushi Mori, M.D.,

Nobuyuki Kato, M.D.

Kenshirou Shiraishi, M.D.,

Hideomi Yamashita, M.D.

Jiro Sato, M.D.,

Akiko Inano, M.D.

Homepage

http://www.m.u-tokyo.ac.jp/mcm/

Introduction and Organization
Department of Radiology was established in 1932.
Radiology covers three major fields that are, Diagnostic Radiology (imaging and intervention), Radiation
Oncology (radiotherapy) and Nuclear Medicine. The
clinical, educational and research activities of our department are being carried out in cooperation with
Department of Radiology in The Research Institute ofMedical Science, which has three (1 associate professor, 1 lecturer, and 1 associate) positions. In addition,
Department of Radiology mainly takes care of radiation protection and radiation safety in the hospital.

Clinical activities
Clinical services on Diagnostic Radiology, Nuclear
Medicine, and Radiation Oncology are provided in thecentralized Clinical Radiology Service Department incooperation with radiology technologists and nurses.

In the section of Diagnostic Radiology, all CT and
MRI examinations are monitored and reported by diagnostic radiologists. Diagnostic radiologists, gastroenterologists and cardiologists mainly perform interventional procedures.
In the section of Nuclear Medicine, there are two
SPECT rooms and two PET rooms. These nuclear
imaging procedures are chiefly performed and reported by radiologists and cardiologists.
Each year, over 700 new patients receive radiation
therapy in the Radiation Oncology section. Highly
accurate 3D radiation therapy is the most outstanding
feature. Stereotactic radiation therapy for small lungor liver tumors was kicked off recently.
In the 9th floor of the new inpatient building, there
are 12 beds in the Radiology ward, which are usuallyused for oncology patients receiving radiation therapy
and chemotherapy. Some of them are sometimes used
for patients receiving invasive diagnostic procedures
such as interventional radiology (IVR), angiography

53

and myelography. There are two special beds for radionuclide (RN) therapy in the same floor. In addition,
four beds are allotted to terminal care ward located in
the 14th floor.

Teaching activities
Lectures are given to the fourth-, fifth- andsixth-year students to provide fundamental knowledgeof diagnostic radiology, radiation oncology and nuclear medicine. Professor, associate professors andlecturers as well as specialists assigned as part timelecturers take part in the education. A series of lectures
about fundamentals of radiology and related sciences
are given to the fourth-year students. As bed-sidelearning (BSL) curriculum, sixteen small groups ofthe fifth-year students are taking part in mini-lecturesand practice to learn basics of diagnostic radiology for
one week. For the sixth-year students, another weekof small group training and mini-lectures are preparedto learn advanced medical techniques of Radiation
Oncology and Nuclear Medicine. They will learn detailed principles of image constructions in various
kinds of imaging modalities and technology in radiation therapy against cancer. Postgraduate students arealso welcome to each of subspecialties of radiology
according to their interests.

Research activities
Research activities in our department include clinical research, animal experiments and development of
instruments as well as computer-based new technology. Diagnostic Radiology group in the department
promotes research activities aiming at efficacy improvement of diagnostic imaging and expansion of its
application. Multi-row detector helical computed tomography (MDCT) enables us to take tomographic
images in three-dimensional (3D) fashion. Using thedata acquired by MDCT various kinds of diseases inalmost all parts of the body, from cerebral diseases tomusculoskeletal diseases, can be displayed in 3D images. New 3D software sdeveloped in our departments
is now widely used in the field of the gastrointestinal
tract, lung, and central nervous system. In addition,
we have opened a new laboratory section named Image Computing and Analysis Laboratory with invita-

tion of a new staff from the Faculty of Engineering,
the University of Tokyo. This section will contributeto development of novel softwares to abstract clinically useful information from the 3D imaging data
more sophisticatedly. In the field of magnetic resonance (MR) imaging, MR digital subtraction angiography, perfusion imaging, and diffusion tensor
imaging are the foci of research. These techniques areaggressively applied to the investigation of vascularand neoplastic diseases of the brain. Application of an
open-type MR imaging unit to interventional radiology is another field of clinical research. In our section,
MR imaging is specifically used to the treatment ofvascular malformation. Basic animal experiments arealso in progress in the field of functional MR imaging
and diffusion and perfusion MR techniques.
Radiation oncology group promotes research projects in two major fields, one is physical engineering
aspect of radiotherapy and the other is reduction of
injuries due to radiation exposure. With the purpose ofachieving precise external irradiation, a new linear
accelerator with C-arm and multileaf collimator systems was developed and installed, which is utilized
mainly for non-coplanar radiation therapy in many
patients especially with brain tumor or head and necktumor. Dynamic conical conformal radiotherapy (Dyconic therapy) for metastatic brain tumors using theaccelerator is under evaluation. In addition to gamma
knife radiosurgery, this new accelerator based stereotactic radiotherapy for brain diseases has been undergone, and stereotactic radiotherapy for body tumors,such as lung and liver tumors, has been investigated. A
new technology to track mobile tumors, represented
by lung tumors is under investigation in collaboration
with accelerator makers. Novel approach to terminal
care of patients with various cancers has been investigated and implemented as the palliative care team incooperation with expert nurses. The relationship between terminal condition and cytokines, and newly
developed scoring system of quality of life are being
evaluated. The gustatory injury due to radiotherapy
has been investigated through animal experiments incombination with the laboratory of biological function,
Graduate School of Agricultural and Life Sciences,
University of Tokyo, and through taste tests in clinicalsetting. Radiation injuries in many tissues in the critically accident in Tokai-mura were also investigated.

54

Nuclear Medicine group promote clinical researchon images of function by the application of radioisotope-labeled tracer technology. In particular, emission
tomography (PET and SPECT) is applied for theevaluation of cerebral blood flow and metabolism inpatients with dementia, epilepsy, and cerebrovasculardiseases. Cerebral blood flow, glucose metabolism andneural synaptic functions are measured for the understanding of normal and pathophysiological states of
CNS disorders, using a variety of positron-emitterradiotracer, such as [O-15] H2O, CO2, O2, CO, [F-18]
FDG, [C-11] methionine, [F-18]Dopa, [C-11]NMSP,NMPB and [C-11] raclopride. The study of dementia
using SPECT and the standard brain atlas has made it
possible to categorize the type of dementia. Evaluation of dopaminergic function by PET is very important in the differential diagnosis of parkinsonism.
Cardiac PET and SPECT are also active fields. Myocardial viability, vascular reserve and sympathetic
nerve denervation in the ischemic heart disease are
evaluated with [F-18] FDG, [N-13] NH3, Tl-201 and[I-123] MIBG. Higher brain functions such as reading,speech and thinking have been studied with PET bycomparing blood flow and receptor binding potential(BP) under various tasks and at rest. For the precise
localization of activated brain function, computer
processing and reconstruction of composite images offunction and anatomy is an essential subject for investigation. At present, whole body FDG-PET is one of
the most effective tool for exploring metastatic lesionsof cancer patients. Combination display of
SPECT/PET with XCT/MRI would be a routine job
and anatomo-functional images would play an important role in the clinical management of the patients.

3)

4)

5)

6)

7)

8)

References
1) Abe O, Yamasue H, Kasai K, Yamada H, Aoki S,
Iwanami A, Ohtani T, Masutani Y, Kato N, Ohtomo K. Voxel-based diffusion tensor analysis reveals aberrant anterior cingulum integrity in posttraumatic stress disorder due to terrorism. Psychiatry Research 146(3): 231-242, 2006
2) Abe O, Yamasue H, Aoki S, Suga M, Yamada H,
Kasai K, Masutani Y, Kato N, Kato N, Ohtomo K.
Aging in the CNS: Comparison of gray/whitematter volume and diffusion tensor data. Neuro-9)biology of Aging, Epub ahead of print, 2006
Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, Kenjyo M, Oya N, Hirota S,
Shioura H, Kunieda E, Inomata T, Hayakawa K,
Katoh N, Kobashi G. Stereotactic radiosurgery
plus whole-brain radiation therapy vs stereotactic
radiosurgery alone for treatment of brain metastases: a randomized controlled trial. The Journal of
the American Medical Association 295(21): 25352536, 2006
Hama Y, Makita K, Yamana T, Dodanuki K.
Mucinous adenocarcinoma arising from fistula inano: MRI findings. American Journal of Roentgenology 187(2): 517-521, 2006
Hashimoto T, Tokuuye K, Fukumitsu N, Igaki H,
Hata M, Kagei K, Sugahara S, Ohara K, Matsuzaki Y, Akine Y. Repeated proton beam therapy
for hepatocellular carcinoma. International Journal of Radiation Oncology, Biology, Physics 65(1): 196-202, 2006
Hata M, Miyanaga N, Tokuuye K, Saida Y, Ohara
K, Sugahara S, Kagei K, Igaki H, Hashimoto T,
Hattori K, Shimazui T, Akaza H, Akine Y. Proton
beam therapy for invasive bladder cancer: a prospective study of bladder-preserving therapy withcombined radiotherapy and intra-arterial chemotherapy.International Journal of Radiation Oncology, Biology, Physics 64(5): 1371-1379, 2006
Hideyama T, Momose T, Shimizu J, Tsuji S, Kwak
S. A positron emission tomography study on therole of nigral lesions in parkinsonism in patientswith amyotrophic lateral sclerosis. Archives of
Neurology 63(12): 1719-1722, 2006
Hori M, Okubo T, Aoki S, Kumagai H, Araki T.
Line scan diffusion tensor MRI at low magnetic
field strength: feasibility study of cervicalspondylotic myelopathy in an early clinical stage.
Journal of Magnetic Resonance Imaging 23(2):183-188, 2006
Igaki H, Tokuuye K, Takeda T, Sugahara S, Hata
M, Hashimoto T, Fukumitsu N, Wu J, Ohnishi K,
Ohara K, Akine Y. Sequential evaluation of hepatic functional reserve by 99mTechnetiumgalactosyl human serum albumin scinitigraphy
after proton beam therapy: a report of three cases
and a review of the literatures. Acta Oncologica
45(8): 1102-1107, 2006

5510) Inoue Y, Izawa K, Tojo A, Sekine R, Okubo T,
Ohtomo K. Light emission requires exposure to
the atmosphere in ex vivo bioluminescence imaging. Molecular Imaging 5(2): 53-56, 200611) Inoue Y, Nomura Y, Haishi T, Yoshikawa K, Seki
T, Tsukiyama-Kohara K, Kai C, Okubo T, Ohtomo
K. Imaging living mice using a 1-T compact magnetic resonance imaging system. Journal of Magnetic Resonance Imaging 24(4): 901-907, 200612) Inoue Y, Tojo A, Sekine R, Soda Y, Kobayashi S,
Nomura A, Izawa K, Kitamura T, Okubo T, Ohtomo K. In vitro validation of bioluminescentmonitoring of disease progression and therapeutic
response in leukaemia model animals. European
Journal of Nuclear Medicine and Molecular Imaging 33(5): 557-565, 2006
13) Inoue Y, Izawa K, Tojo A, Nomura Y, Sekine R,
Oyaizu N, Ohtomo K. Monitoring of disease progression by bioluminescence imaging and magnetic resonance imaging in an animal model ofhematologic malignancy. Experimental Hematology 35(3): 407-415, 200714) Ishizawa T, Sugawara Y, Hasegawa K, Ikeda M,
Akahane M, Ohtomo K, Makuuchi M. Splenic artery aneurysm after liver transplantation. Journalof Gastroenterology and Hepatology 21(7): 1213,
200615) Itoh D, Aoki S, Maruyama K, Masutani Y, Mori H,
Masumoto T, Abe O, Hayashi N, Okubo T, Ohtomo K. Related articles, links corticospinal tracts
by diffusion tensor tractography in patients witharteriovenous malformations. Journal of Computer Assisted Tomography 30(4): 618-623, 200616) Iwase S, Murakami T, Saitou Y, Nakagawa K.
Preliminary stastical assessment of intervention
by a palliative care team working in a Japanesegeneral inpatient unit. American Journal of Hospice & Palliative Medicine 24(1): 1-7, 200717) Kamada K, Todo T, Masutani Y, Aoki S, Ino K,
Morita A, Saito N. Visualization of the frontotemporal language fibers by tractography combined with functional magnetic resonance imaging
and magnetoencephalography. Journal of Neurosurgery 106(1): 90-98, 200718) Kiryu S, Watanabe M, Kabasawa H, Akahane M,
Aoki S, Ohtomo K. Evaluation of super paramagnetic iron oxide-enhanced diffusion-weighted

PROPELLER T2-fast spin echo magnetic resonance imaging: Preliminary experience. Journal ofComputer Assisted Tomography 30(2): 197-200,
200619) Kiryu S, Okubo T, Takeuchi K, Inoue Y, Endo T,
Odawara T, Nakamura T, Aoki S, Ohtomo K.
Magnetic resonance imaging and diffusion tensor
analysis of lymphomatoid granulomatosis of thebrain. Acta Radiologica 47(5): 509-513, 200620) Kiryu S, Loring SH, Mori Y, Rofsky NM, Hatabu
H, Takahashi M. Quantitative analysis of the velocity and synchronicity of diaphragmatic motion:
dynamic MRI in different postures. Magnetic
Resonance Imaging 24(10):1325-1332, 200621) Kudo N, Kasai K, Itoh K, Koshida I, Yumoto M,
Kato M, Kamio S, Araki T, Nakagome K, Fukuda
M, Yamasue H, Yamada H, Abe O, Kato N, Iwanami A. Comparison between mismatch negativity
amplitude and magnetic mismatch field strength
in normal adults. Biological Psychology 71(1):54-62, 200622) Kuwabara K, Nishishita T, Morishita M, Oyaizu N,
Yamashita S, Kanematsu T, Obara T, Mimura Y,
Inoue Y, Kaminishi M, Kaga K, Amino N, Kitaoka M, Ito K, Miyauchi A, Noguchi S, Uchimaru K, Akagawa E, Watanabe N, Takahashi TA,
Sato K, Inazawa T, Nakaoka T, Yamashita N. Results of a phase I clinical study using dendritic
cell vaccinations for thyroid cancer. Thyroid
17(1): 53-58, 200723) Li Z, Hosoi Y, Cai K, Tanno Y, Matsumoto Y,
Enomoto A, Morita A, Nakagawa K, Miyagawa K.
Src tyrosine kinase inhibitor PP2 suppresses
ERK1/2 activation and epidermal growth factor
receptor transactivation by X-irradiation. Biochemical and Biophysical Research Communications 341(2): 363-368, 200624) Maeda E, Akahane M, Kato N, Hayashi N, Koga
H, Yamada H, Kato H, Ohtomo K. Assessment ofmajor aortopulmonary collateral arteries (MAPCAs) with multidetector-row computed tomography. Radiation Medicine 24(5): 378-383, 200625) Maeda E, Uozumi K, Kato N, Akahane M, Inoh S,
Inoue Y, Beck Y, Goto A, Makuuchi M, Ohtomo K.
MR findings of eile duct adenoma with calcification. Radiation Medicine 24(6): 459-462, 200626) Maeda E, Akahane M, Watadani T, Yoshioka N,

56

Goto A, Sugawara Y, Makuuchi M, Ohtomo K.
Isolated hepatic hemangiomatosis in adults: reportof two cases and review of the literature. European Journal of Radiology extra 61(1): 9-14, 200727) Maeda E, Akahane M, Uozaki H, Kato N, Hayashi
N, Fukayama M, Ohtomo K. CT appearance of
Epstein-barr virus associated gastric carcinoma.
Abdominal Imaging, in press
28) Maeda T, Fujii T, Matsumura T, Endo T, Odawara
T, Itoh D, Inoue Y, Okubo T, Iwamoto A, Nakamura T. AIDS-related cerebral toxoplasmosis withhyperintense focion T1-weighted MR images: A
case report. The Journal of Infection 53(4):e167-e170, 200629) Maruyama K, Shin M, Tago M, Kurita H, Kawahara N, Morita A, Saito N. Management and outcome of hemorrhage after gamma knife surgery
for arteriovenous malformations of the brain.
Journal of Neurosurgery 105(supplment): 52-57,
200630) Maruyama K, Shin M, Tago M, Kishimoto J, Morita A, Kawahara N. Radiosurgery to reduce therisk of first hemorrhage from brain arteriovenous
malformations. Neurosurgery 60(3): 453-459,
200731) Masutani Y, Uozumi K, Akahane M, Ohtomo K.
Liver CT image processing: A short introductionof the technical elements.European Journal of Radiology 58(2): 246-251, 200632) Matsumoto Y, Nakagawa S, Yano T, Takizawa S,
Nagasaka K, Nakagawa K, Minaguchi T, Wada O,
Ooishi H, Matsumoto K, Yasugi T, Kanda T, Huibregtse JM, Taketani Y. Involvement of a cellularubiquitin-protein ligase E6AP in the ubiquitin-mediated degradation of extensive substrates
of high-risk human papillomavirus E6. Journal of
Medical Virology 78(4):501-507, 200633) Mitsui J, Saito Y, Momose T, Shimizu J, Arai N,
Shibahara J, Ugawa Y, Kanazawa I, Tsuji S, Murayama S. Pathology of the sympathetic nervous
system corresponding to the decreased cardiac
uptakein
123I-metaiodobenzylguanidine(MIBG)scintigraphy in a patient with Parkinson
disease. Journal of the Neurological Sciences
243(1-2): 101-104, 200634) Morita A, Zhu J, Suzuki N, Enomoto A, Matsumoto Y, Tomita M, Suzuki T, Ohtomo K, Hosoi Y.

Sodium orthovanadate suppresses DNA damage-induced caspase activation and apotosis byinactivating p53. Cell Death and Differentiation
13(3): 499-511, 200635) Nagasaka K, Nakagawa S, Yano T, Takizawa S,
Matsumoto Y, Tsuruga T, Nakagawa K, Minaguchi T, Oda K, Hiraike-Wada O, Ooishi H, Yasugi T,
Taketani Y. Human homolog of Drosophila tumor
suppressor
Scribblenegatively
regulatescell-cycle progression from G1 to S phase by localizing at the basolateral membrane in epithelial
cells. Cancer Science 97(11): 1217-1225, 200636) Nakagawa K, Yoda K, Shiraki T, Sasaki K, Miyazawa M, Ishidoya T, Ohtomo K, Hamada M. Radiophotoluminescence dosimetry using a small
spherical glass: A preliminary phantom study. Radiation Protection Dosimetry, Epub ahead of print,
200637) Nakamura K, Shioyama Y, Kawashima M, Saito Y,
Nakamura N, Nakata K, Hareyama M, Takada T,
Karasawa K, Watanabe T, Yorozu A, Tachibana H,
Suzuki G, Hayabuchi N, Toba T, Yamada S.
Multi-institutional analysis of early squamous cell
carcinoma of the hypopharynx treated with radical
radiotherapy. International Journal of Radiation
Oncology, Biology, Physics. 65(4): 1045-1050,
200638) Nakamura N, Igaki H, Yamashita H, Shiraishi K,
Tago M, Sasano N, Shiina S, Omata M, Makuuchi
M, Ohtomo K, Nakagawa K. A retrospective studyof radiotherapy for spinal bone metastases fromhepatocellular carcinoma (HCC). Japanese Journal of Clinical Oncology 37(1): 38-43, 200639) Nakata Y, Yagishita A, Arai N. Two patients withintraspinal germinoma associated with Klinefelter
syndrome: Case report and review of the literature.
American Journal of Neuroradiology 27(6):1204-1210, 200640) Nakata Y. Intraspinal germinoma associated with
Klinefelter syndrome: a case report and review ofliterature. American Journal of Neuroradiology, inpress41) Nomura Y, Inoue Y, Yokoyama I, Nakaoka T, Itoh
D, Okubo T, Ohtomo K. Evaluation of left ventricular function with cardiac magnetic resonanceimaging using Fourier fitting. Magnetic Resonance Imaging 24(10): 1333-1339, 2006

5742) Ohgami Y, Kotani Y, Tsukamoto T, Omura K,
Inoue Y, Aihara Y, Nakayama M. Effects ofmonetary reward and punishment on stimulus-preceding negativity. Psychophysiology 43(3):227-236, 2006
43) Ohtomo K. Liver MRI update. European Journalof Radiology 58(2): 163-164, 200644) Seki C, Momose T, Kojima Y, Ohtomo K, Yokoyama I. Proposal of blood volume-correctedmodel for quantification of regional cerebral
blood flow with H2 15O-PET and its application
to AVF. Radiation Medicine 24(4): 260-268, 200645) Takahashi M, Momose T, Kameyama M, Ohtomo
K. Abnormal accumulation of [18-F] Fluorodeoxyglucose in the aortic wall related to inflammatory chages: three case reports. Annals of Nuclear Medicine 20(5): 361-364, 200646) Takizawa S, Nagasaka K, Nakagawa S, Yano T,
Nakagawa K, Yasugi T, Takeuchi T, Kanda T,
Huibregtse JM, Akiyama T, Taketani Y. Humanscribble, a novel tumor suppressor identified as atarget of high-risk HPV E6 for ubiquitin-mediateddegradation, interacts with adenomatous polyposiscoli. Genes to Cells 11(4): 453-464, 200647) Tonotsuka N, Hosoi Y, Miyazaki S, Miyata G,
Sugawara K, Mori T, Ouchi N, Satomi S, Matsumoto Y, Nakagawa K, Miyagawa K, Ono T. Heterogeneous expression of DNA-dependent protein
kinase in esophageal cancer and normal epithelium. International Journal of Molecular Medicine
18(3): 441-447, 200648) Tsukamoto T, Kotani Y, Ohgami Y, Omura K,
Inoue Y, Aihara Y. Activation of insular cortex andsubcortical regions related to feedback stimuli in atime estimation task: an fMRI study. Neuroscience Letters 399(1-2): 39-44, 2006
49) Uno K, Takenaka K, Asada K, Ebihara A, Sasaki
K, Komuro T, Nagai R, Motomura N, Ono M,
Takamoto S. Diagnosis of subacute cardiac rupture by contrast echocardiography. Journal of theAmerican Society of Echocardiography 19(11):1401.e9-1401.e11, 2006
50) Watanabe M, Aoki S, Masutani Y, Abe O, Hayashi
N, Masumoto T, Mori H, Kabasawa H, Ohtomo K.
Flexible ex vivo phantoms for validation of diffusion tensor tractography on a clinical scanner. Radiation Medicine 24(9): 605-609, 2006

51) Yamamoto KK, Miyata T, Momose T, Nagayoshi
M, Akagi D, Hosaka A, Miyahara T, Ishii S, Kimura H, Deguchi J, Shigematsu K, Shigematsu H,
Nagawa H. Reduced vascular reserve measured bystressed single photon emission computed tomography carries a high risk for stroke in patientswith carotid stenosis. International Angiology
25(4): 385-388, 2006
52) Yamashita H, Nakagawa K, Tago M, Igaki H,
Shiraishi K, Nakamura N, Sasano N, Yamakawa S,
Ohtomo K. Small bowel perforation without tumor recurrence after radiotherapy for cervicalcarcinoma: report of seven cases. The Journal of
Obstetrics and Gynaecology Research 32(2):235-42, 2006
53) Yamashita H, Nakagawa K, Tago M, Nakamura N,
Shiraishi K, Eda M, Nakata H, Nagamatsu N,
Yokoyama R, Onimura M, Ohtomo K. Taste dysfunction in patients receiving radiotherapy. Head& Neck 28(6): 508-516, 2006
54) Yamashita H, Izutsu K, Nakamura N, Shiraishi K,
Chiba S, Kurokawa M, Tago M, Igaki H, Ohtomo
K, Nakagawa K. Treatment results of chemoradiation therapy for localized aggressive lymphomas:
A retrospective 20-year study. Annals of Hematology 85(8): 523-529, 2006
55) Yamashita H, Nakagawa K, Shiraishi K, Tago M,
Igaki H, Nakamura N, Sasano N, Shiina S, Omata
M, Ohtomo K. External beam radiotherapy totreat intra- and extra-hepatic dissemination ofhepatocellular carcinoma after radiofrequency
thermal ablation. Journal of Gastroenterology andHepatology 21(10): 1555-1560, 2006
56) Yamashita H, Nakagawa K, Tago M, Nakamura N,
Shiraishi K, Mafune K, Kaminishi M, Ohtomo K.
The intergroup/RTOG 85-01 concurrent chemoradiation regimen for Japanese esophageal cancer.
Hepatogastroenterology 53(72): 863-868, 2006
57) Yamashita H, Nakagawa K, Nakamura N, Abe K,
Asakage T, Ohmoto M, Okada S, Matsumoto I,
Hosoi Y, Sasano N, Yamakawa S, Ohtomo K. Relation between acute and late irradiation impairment of four basic tastes and irradiated tongue
volume in patients with head-and-neck cancer.
International Journal of Radiation Oncology, Biology, Physics 66(5): 1422-1429, 2006
58) Yamashita H, Nakagawa K, Shiraishi K, Tago M,

58

Igaki H, Nakamura N, Sasano N, Siina S, Omata
M, Ohtomo K. Radiotherapy for lymph node metastases in patients with hepatocellular carcinoma:
Retrospective study. Journal of Gastroenterolgy
and Hepatology 22(4): 523-527, 2007
59) Yamasue H, Abe O, Kasai K, Suga M, Iwanami A,
Yamada H, Tochigi M, Ohtani T, Rogers MA, Sasaki T, Aoki S, Kato T, Kato N. Human brain
structural change related to acute single exposure
to sarin. Annals of Neurology 61(1): 37-46, 2007
60) Yamazaki T, Suzuki J, Shimamoto R, Tsuji T,
Ohmoto Y, Toyo-oka T, Omata M, Ohtomo K,
Nagai R. Focalized contractile impairment at hypertrophied myocardium proven in considerationof wall stress in patients with hypertrophic cardiomyopathy. International Heart Journal 47(2):247-258, 2006
61) Yokoyama I, Inoue Y, Moritan T, Ohtomo K, Nagai R. Myocardial glucose utilisation in type II
diabetes mellitus patients treated with sulphonylurea drugs. European Journal of Nuclear Medicine and Molecular Imaging 33(6): 703-708, 2006
62) Yoshikawa T, Hayashi N, Yamamoto S, Tajiri Y,
Yoshioka N, Masumoto T, Mori H, Abe O, Aoki S,
Ohtomo K. Brachial Plexus Injury: Clinical
Manifestations, Conventional Imaging Findings,
and the Latest Imaging Techniques. Radiographics
26(supplment1): S133-S143, 2006
63) Yoshioka N, Hayashi N, Akahane M, Yoshikawa T,
Takeshita K, Ohtomo K. Bezier surface reformation: an original visualization technique of cervical myelographic CT. Radiation Medicine 24(8):600-604, 2006

60

Department of
System Physiology
Professor
Joji Ando, M.D.,Ph.D.

Lecturer
Masahiro Shibata, Ph.D.,

Homepage

Kimiko Yamamoto, M.D.,Ph.D.

http://bme-sysphysiol.m.u-tokyo.ac.jp

Introduction and Organization
Our department originated from the Institute ofMedical Electronics, established in 1961. In 1997, as aresult of the shift to the chair system of the Graduate
School of Medicine, the Institute was replaced withthree departments of Biomedical Engineering: System
Physiology, Bioimaging and Biomagnetics, and Biosystem Construction and Control. The Department of
System Physiology consists of one professor and two
lecturers.

Teaching activities
We provide lectures of “Early Exposure to Medicine” for second year students, “Basic Principles ofBiomedical Engineering” for second and third year
students, “Introduction to Biomedical Engineering”
for postgraduate students in the faculty of Medicine,and “Principles of Medicine” for postgraduate students in the faculty of Engineering. We offer practicaltraining of biomedical engineering research to thirdand fourth year medical students. A weekly seminar isheld in our laboratory bringing together staff, postgraduate students and research fellows to discuss
journal articles and give updates on experiments. Our
aim is to enhance the research skills of students.

Research activities
This laboratory has been pursuing the study of bio-mechanics dealing with mechanical phenomena in thehuman body, especially focusing on cellular sensing
and response mechanisms to mechanical stimuli. The
main theme of our work is the relationships between
shear stress, a mechanical force generated by blood
flow, and its target cells, vascular endothelial cells.
This would be of benefit not only to understanding
blood flow-mediated regulation of vascular functions
but also to the elucidation of clinically important
problems such as angiogenesis, vascular remodelingand atherogenesis which occur in a blood flowdependent manner.
Original biomedical engineering methods have been
applied, in which cultured endothelial cells are exposed to controlled levels of shear stress in a
fluid–dynamic flow apparatus and whose responses
are analyzed at the cellular and molecular levels. Microcirculatory hemodynamics and oxygen transport
are studied by employing opto-electronics technology.
The results of these experiments are listed below.
1. Cell responses to shear stress
2. Shear stress-mediated gene regulation
3. Shear stress signal transduction
4. Oxygen dynamics and microvascular energetics
1. Cell responses to shear stress
Our studies have demonstrated that endothelial cells
have functional responses to shear stress. When a cultured endothelial cell monolayer was partially denuded, surrounding cells migrated and proliferated in

61

the denuded area, and covered the denuded area. Shearstress enhanced the regenerative functions of endothelial cells (Microvasc Res 1987, Biorheology, 1990).
Shear stress increased the production of nitric oxide, apotent vasodilator, in endothelial cells in adose-dependent manner (BBRC 1994). Shear stressalso increased the expression of thrombomodulin, an
antithrombotic molecule, in endothelial cells (BBRC
1994). In contrast, it decreased the expression of vascular cell adhesion, which leads to the inhibition ofleukocyte adhesion to vascular cell adhesion molecule-1 (VCAM-1; BBRC 1993, Am J Physiol 1994). A
collaborative study showed that shear stress increases
the levels of adrenomedulin and C-type natriuretic
peptide mRNA which have vasodilating effects in addition to nitric oxide (Hypertension 1997), and that it
also augmented the expression of lectin like low density lipoprotein receptor (LOX-1) at the protein andmRNA level (Circ Res 1998). Recently, we revealed
that endothelial progenitor cells (EPCs) circulating inhuman peripheral blood proliferate and differentiate
into mature endothelial cells in response to shear
stress, thereby forming tube-like structures in collagengel (J Appl Physiol 2003). We also found that shear
stress induces the differentiation of murine embryonicstem cells (ES cells) into endothelial cells in vitro(Am J Physiol 2005). Based on these findings, in acollaborative study, a new type of artificial bloodvessel, in which ES cells were cultured in polymer
tubes and exposed to pulsatile shear stress, was developed (J Artif Organs 2005).
2. Shear stress-mediated gene regulation
We have demonstrated that shear stress regulates
endothelial gene expression transcriptionally and/or
posttranscriptionally. Shear stress downregulates
VCAM-1 gene transcription via the double AP-1
binding element (TGACTCA) in the promoter whichfunctions as a shear stress-responsive element (Am J
Physiol 1997). Shear stress has also been shown toincrease the level of granulocyte/macrophase-colony
stimulating factor (GM-CSF) via mRNA stabilization(Circ Res 1988). Differential display analysis showedthat around 600 known and unknown transcripts wereup- or down-regulated in human umbilical vein endothelial cells exposed to a shear stress of 15 dynes/cm2
for 6 h (BBRC 1996). From these shear stress-

responsive genes, a cDNA encoding an unknown
G-protein coupled receptor was cloned (BBRC 1997).
We showed that the transcription factor SP1 is involved in the shear stress-induced down-regulation of
P2X4 (an ATP-gated cation channel) gene expressionin endothelial cells (Am J Physiol 2001). DNA microarray analysis revealed that approximately 3% of
the all endothelial genes, which corresponds to about
600 genes, respond to shear stress (J Athero Thromb
2003). We revealed that endothelial genes are differentially regulated by laminar and turbulent shear stress.
Laminar shear stress decreases the gene expression of
urokinase plasminogen activator (uPA), which plays arole in fibrinolysis and vascular remodeling, via both
GATA6-mediated down-regulation of gene transcription and an acceleration of mRNA degradation, while
turbulent shear stress increases the uPA gene expression through mRNA stabilization (Am J Physiol 2004).
Recently, we found that hepatocytes are flow-sensitive.
Hepatocyte PAI-1 gene expression was up-regulatedby shear stress through cooperative Sp1/Ets-1 activation of transcription (Am J Physiol2006).
3. Shear stress signal transduction
We first showed that Ca2+ signalling plays an important role in the mechanism by which endothelial
cells recognize the shear stress signal and transmit itinto the cell interior（In Vitro Cell Dev Biol 1988.
Strong shearing forces induced by dragging endothelial cells with a balloon causes an increase in cytoplasmic Ca2+ concentrations (Biorheology 1994). A
relatively weak shearing force like shear stress generated by fluid flow needs the presence of extracellular
ATP to induce Ca2+ response, and at several hundred
nanomolar of ATP, intracellular Ca2+ concentrations
increase in a shear stress-dependent manner (BBRC
1991, 1993). Generally, flow-induced Ca2+ responses
are initiated at a locus at the cell edge and propagate
throughout the entire cell in the form of a Ca2+ wave.
The initiation locus corresponded precisely to caveolae rich cell edges (Proc Natl Acad Sci 1998). We
found that a subtype of ATP-gated cation channel, theP2X4 receptor, is expressed in human vascular endothelial cells (Am J Physiol 2000) and that P2X4 receptors play a crucial role in the shear stressdependent Ca2+ response (Circ Res 2000). Endogeneously released ATP by shear stress is involved in the

62

P2X4-mediated Ca2+ responses (Am J Physiol 2003).
Recently, we produced P2X4-deficient mice and observed that the P2X4-deficent mice have impaired
flow-dependent control of vascular tone and remodeling, indicating that shear stress signal transduction via
P2X4 plays a critical role in the regulation of circulatory functions (Nat Med 2006).
4. Oxygen dynamics and microvascular energetics
For nearly 100 years, the capillary is believed to be
the sole source of oxygen supply to surrounding tissue.
By using an originally developed laser microscopic
system (Med Biol Eng Comput 1999), we found a significant downstream drop in the arteriolar oxygen
level (J Appl Physiol 2001), and clarified that thisdrop in oxygen was caused by oxygen supply to tissue
from arterioles (Eur J Appl Physiol 2005, 2006). Furthermore, we have examined the effect of vessel wall
oxygen consumption on the oxygen drop in arterioles.
We found that the vascular wall oxygen consumption
in functional arterioles was more than 100 times
greater than the values reported in in vitro experiments,
and the oxygen consumption depends on the total
amount of workload of vascular smooth muscle (Am J
Physiol 2005a). We have also studied the relationshipbetween the endothelium derived nitric oxide andoxygen transport to tissue, and clarified the physiological role of nitric oxide as a modulator of tissue
oxygenation by reducing oxygen consumption byvessel walls (Am J Physiol 2005b, J Appl Physiol
2006).

References(1) Sugiyama S, Yamamoto K, Nishimura N, Nakagawa M, Maruta Y, Ando J. Adequate design ofcustomized cDNA microarray for convention
multiple gene expression analysis. J. Biosci. Bioeng. 2007; 103: 74-81.
(2) Nakatsuka H, Sokabe T, Yamamoto K, Sato Y,
Hatakeyama K, Kamiya A, Ando J. Shear stressinduces hepatocyte PAI-1 gene expression thorugh cooperative Sp1/Ets-1 activation of transcription. Am. J. Phsyiol. Gastrointest. Liver
Physiol. 2006; 291: G26-G34.
(3) Mackley JR, Ando J, Herzyk P, Winder SJ. Phenotypic responses to mechanical stress in fibro-

blasts from tendon, cornea and skin. Biochem. J.
2006; 396: 307-316.
(4) Nakamura M, Mie M, Funabashi H, Yamamoto K,
Ando J, Kobatake E. Cell-surface-localized ATP
detection with immobilized firefly luciferase.
Anal. Biochem. 2006; 352: 61-67.
(5) Yamamoto K, Sokabe T, Matsumoto T, Yoshimura
K, Shibata M, Ohura N, Fukuda T, Sato T, Sekine K,
Kato S, Isshiki M, Fujita T, Kobayashi M, Kawamura K, Masuda H, Kamiya A, Ando J. Impaired
flow- dependent control of vascular tone and remodeling in P2X4-deficient mice. Nat Med. 2006;
12: 133-137.
(6) Yamamoto K, Sokabe T, Watabe T, Miyzono K, Yamashita JK, Obi S, Ohura N, Matsushita A, Kamiya A,
Ando J. Fluid shear stress induces differentiation of
Flk-1-positive embryonic stem cells into vascular endothelial cells in vitro. Am J Physiol Heart Circ Physiol.
2005; 288: H1915-H1924.
(7) Huang H, Nakayama Y, Qin K, Yamamoto K,
Ando J, Yamashita JK, Itoh H, Kanda K, Yaku H,
Okamoto Y, Nemoto Y. Differentiation from embryonic stem cells to vascular wall cells under in vitro pulsatile flow loading. J Artif Organs. 2005; 8: 110-118.
(8) Chen YM, Shiraishi N, Satokawa H, Kakugo A,
Narita T, Gong JP, Osada Y, Yamamoto K, Ando J.
Cultivation of endothelial cells on adhesive protein-free synthetic polymer gels. Biomaterials.
2005; 26: 4588-4596.
(9) Shibata M, Qin K, Ichioka S, Kamiya A. Vascularwall energetics in arterioles during nitric oxide
dependent and independent vasodilation. J Appl
Physiol. 2006; 100: 1793-1798.
(10) Shibata M, Ichioka S, Togawa T, Kamiya A. Arterioles’ contribution to oxygen supply to skeletal
muscles at rest. Eur J Appl Physiol. 2006; 97:327-331(11) Ohura N, Kurita T, Takishima A, Shibata M, Harii
K. Efficacy of a skin-protection power for use asa dressing for intractable ulcers. J Wound Care.
2006; 15: 471-478(12) Shibata M, Ichioka S, Ando J, Togawa T, Kamiya A.
Non-linear regulation of capillary perfusion in relation to ambient pO2 changes in skeletal muscle. Eur
J Appl Physiol. 2005;94:352-355.
(13) Shibata M, Ichioka S, Kamiya A. Estimating oxygen
consumption rates of arteriolar walls under physiologi-

63

cal conditions in rat skeletal muscle. Am J Physiol Heart
Circ Physiol. 2005;289:H295-H300.
(14) Shibata M, Ichioka S, Kamiya A. Nitric oxide
modulates oxygen consumption by arteriolar walls
in rat skeletal muscle. Am J Physiol Heart Circ
Physiol. 2005;289:H2673-H2679.
(15) Ohura N, Ichioka S, Nakatsuka T, Shibata M.
Evaluating dressing materials for the prevention ofshear force in the treatment of pressure ulcers. J
Wound Care. 2005;14:401-404.
(16)Asano Y, Ichioka S, Shibata M, Ando J, Nakatsuka T.
Sprouting from arteriovenous shunt vessels with increased flow. Med Biol Eng Comput. 2005;43:
126-130.

64

Department of Biosystem
Construction & Control
Associate Professor
Yusuke Abe, M.D., Ph.D.

Assistant Professor
Takashi Isoyama, Ph.D.

Homepage

http://www.bme.rcast.u-tokyo.ac.jp/

Introduction and Organization
Institute of Medical Electronics was established in
1963 as the first research institute for medical engineering in Japan. Department of Clinical Medicine in
the Institute of Medical Electronics was started in1964 for research and development of the advanced
diagnostic and therapeutic medical engineering technologies for clinical medicine. To date, medical engineering is not only a very important academic discipline but also a very important means for the clinicalmedicine. The name of the department and institutehas been changed as shown above since April 1, 1997
with the structural reform of Faculty of Medicine.
As the research field covers interdisciplinary andcomprehensive researches based on the medical andengineering technique, we are cooperating with various laboratories. Especially, Research Center for Advanced Science and Technology (RCAST), Department of Information Physics and Computing (IPC),
Graduate School of Information Science and Technology and Tohoku University Biomedical Engineering Research Organization (TUBERO) have beenclosely contacting and performing cooperative researches with us. Our doctor course students can perform research work under the teaching of Prof. Mabuchi at IPC.

Teaching activities
As for under-graduate education, our department

takes a part in systematic lectures for the 3rd year
medical students, and provides practice in the freequarter course and other short-term course for the 3rd
and 4th year medical students. In systematic lectures,
basic knowledge about the advanced diagnostic andtherapeutic medical engineering technologies and artificial organ technologies are presented. The basic lecture of medical electronics is included.
As for post-graduate education, our department
takes a part in series of lectures for doctor course andmaster course students. In the lectures for mastercourse students, artificial organ technologies are presented. In the lectures for doctor course students, philosophy, methodology and basic and special knowledge about medical engineering for basic and clinicalmedicine are presented.
The educational practice of the post-graduate students is performed mainly by on-the-job training
method in the daily research works. Especially,
pre-operative management, anesthesia, surgery,post-operative management, measurement, data processing, ethical factor, and so on are learned throughthe animal experiment of artificial heart. As for the
subject of research, students find it by themselvesfrom not only the field of artificial organs but also thewide area of medical engineering field. On the other
hand, the education to train the leaders of biomedical
engineer and clinical engineer is another importantrole. Other than the medical students, many students
come from engineering department of our university
and other university such as Waseda University and65

Kitasato University. Students must attend to weekly
meeting. They can learn how to perform the research
work and how to report it through this meeting.

Research activities
Our research field covers advanced diagnostic andtherapeutic medical engineering technologies forclinical medicine. The main themes are artificial organs (artificial heart, assist circulation, artificial lung,artificial valve, tissue engineered artificial organs,regenerative artificial organs, etc). Especially, artificial heart is the world famous research project having
a long history since 1959 at the University of Tokyo.
Almost all the researches and developments such as
driving mechanism, energy converter, blood pumps,
artificial valves, biomaterials, power transmission,
measurement techniques, control methods, anatomicalcompatibility, hemocompatibility, tissue compatibility,
computer fluid dynamics, physiology, pathology, andso on, have been studied. All the stuffs and students
join to this project. In 1995, we succeeded to survivea goat for 532 days with the paracorporial total artificial heart (TAH), which is still the longest survival
record of TAH animals in the world.
Our artificial heart research at present focuses todevelop an implantable next generation TAH. We invented a small continuous-flow blood pump with highperformance, named undulation pump, to meet the
purpose. We are developing an undulation pumptotal artificial heart (UPTAH) that is the most compact
implantable TAH with the highest performance inproducing output in the world. This TAH is designed to generate pulsatile flow by changing motor
speed periodically. Recently, the new model of
UPTAH was developed for the purpose of studying
physiology with nonpulsatile TAH. This UPTAH canswitch pulsatile flow to nonpulsatile flow with a single device easily. We succeeded to survive a goat for
72 days with UPTAH without any anticoagulant.
How to control the output of TAH is another big
interest. We have developed our original control
method, named 1/R control, in which the cardiac output is controlled by the cardiovascular center throughthe feedback mechanism using changes in total peripheral resistance and arterial pressure. At the present
time, the 1/R control is the single method to realize aphysiological control of the output of TAH, in which
the particular problems of TAH such as venous hypertension, slight anemia, low thyroid hormone level,and so on, are not occurred and the output is changedin accordance with metabolic condition of the animal.
The 1/R control was installed in the UPTAH and thepathphysiological study is being performed.
Concerning the biomaterials, the mechanism ofthrombus formation and calcification on the medical
polymer surfaces, especially in the artificial heart andon the polymer valve have been studied. Recently, wedeveloped tissue engineered insert molding method
for making parts of artificial organs. This method will
be important technique for developing next generation
artificial organs.
An implantable probe for observation of microcirculation has been developed using CCD chip. This
device is expected to progress the physiology of the
microcirculation with TAH. The new implantableprobe for observation of angiogenesis in tissue engineered material using CMOS camera is under the development.
Nerve interface will be very important technology
for developing control mechanism of artificial organs.
The basic study to develop a multiple interface arrayfor single nerve fibers is being studied using micromachine technique.

References
1. Imachi K, Saito I, K. Takiura K, Chinzei T,
Isoyama T, Yambe T, Shiraishi Y, Miura H,
Matsuki H, Mitamura Y, Inoue Y, Okamoto E,
Umezu M, Nemoto I, Abe Y: Compact ventricularassist device and total artificial heart using
undulation pump. Proc World Congress on
Medical Physics and Biomedical Engineering
2006, 3021-3025, T18-4501
2. Imachi K, Mochizuki S, Baba A, Isoyama T, Saito
I, Takiura K, Chinzei T, Shiraishi Y, Yambe T, Abe
Y: An implantable probe for chronic observationof microcirculation. Proc World Congress on
Medical Physics and Biomedical Engineering
2006, 2219-2223, T14-3947
3. Okamoto E, Makino T, Nakamura M, Tanaka S,
Chinzei T, Abe Y, Isoyama T, Saito I, Mochizuki S,
Imachi K, Inoue Y, Mitamura Y: Numerical esti-

66

4.

5.

6.

7.

8.

9.

mation of heat distribution from implantable battery system of undulation pump. J. Artif Organs,
9:77-83, 2006
Okamoto E, Makino T, Inoue Y, Tanaka S, Yasuda
T, Nakamura M, Saito I, Abe Y, Chinzei T,
Isoyama T, Mochizuki S, Imachi K, Mitamura Y:
Development of Integrated Electronic Unit for
Drive and Control of Undulation Pump LVAD.
Artificial Organs, 30(5):403-405, 2006
Makino T, Okamoto E, Tanaka S, Yasuda T, Inoue
Y, Saito I, Isoyama T, Chinzei T, Mochizuki S,
Abe Y, Imachi K, Mitamura Y: Estimation of earlystage malfunction using implantable artificial
heart sound in animal experiments. Artificial Organs, 30(5):360-364, 2006
Fukayama O, Taniguchi N, Suzuki T, Mabuchi K:
Estimation of Locomotion Speed and Directions
Changes to Control a Vehicle using Neural Signals from the Motor Cortex of Rat. Proc 28th
Annual International Conference of the IEEEEMBS, 3873-3876, 2006
Hoshino T, Ozasa A, Kometani R, Suzuki T, Matsui S, Mabuchi K: Development of a Regeneration-type Neural Interface: A Microtube Guide for
Axon Growth of Neuronal Cells Fabricated Using
Focused-ion-beam Chemical Vapor Deposition. J
Vacuum science and Tech 24(6):2538-2543, 2006
Imachi K, Mochizuki S, Baba A, Isoyama T, Saito
I, Takiura K, Chinzei T, Shiraishi Y, Yambe T, Abe
Y: Development of implantable probe for observation of microcirculation, Biocybernetics andBiomed Eng, 27:45-52, 2007
Abe Y, Isoyama T, Saito I, Mochizuki S, Ono M,
Nakagawa H, Taniguchi N, Mitsumune N, Sugino
A, Mitsui M, Takiura K, Ono T, Kouno A, Chinzei
T, Takamoto S, Imachi K: Development of mechanical circulatory support device at the university of Tokyo. J Artif Organs, 10:60-70, 2007

68

Department of Neuropathology
Professor
Yasuo Ihara, M.D.

Associate Professor
Lecturer
Maho Morishima-Kawashima, Ph.D.

Associate
Satoru Funamoto, Ph.D.,

Tomohiro Miyasaka, Ph.D.

Homepage
Introduction and Organization

Teaching activities

The Institute for Brain Research to which Department of Neuropathology originally belonged is dated
back to 1935, when three laboratories were set to start
brain research within the Department of Psychiatry.
The first lab was headed by Dr. Teizo Ogawa, thesecond by Dr. Shufu Yoshimasu, and the third by Dr.
Katsumi Kakeda. In 1953, the Institute for Brain Research was formally established, which consisted ofsix departments, namely Departments of Neuropathology, Neuroanatomy, Neurophysiology, Neurochemistry, and Psychology. In 1959, Dr. Hirotsugu
Shiraki promoted to the first professor of Neuopathology, followed by Drs. Tatsuya Yamamoto and
Masanori Tomonaga. In 1991, Dr. Yasuo Ihara succeeded the professorship, and became the fourth professor of Neuropathology. In 1997, the Institute wasclosed as the Faculty of Medicine, University of Tokyo was promoted to the Graduate School of Medicine.
By extensive reorganization, Department of Neuropathology now makes up the Neuroscience Division,
together with Departments of Neurochemistry, Neurobiology (formerly Psychology), Neurology, Neurosurgery, and Psychiatry, and three departments fromthe Institute for Phonetics.

As we belonged to the research institute in the past,
we have not been heavily involved in the teachingactivities. What we are presently involved are to provide lectures on Alzheimer’s disease and neuroanatomy to premedical students, and master course students. For these five years intensive neuroanatomy
course has been provided towards doctoral and masterstudents every January for a period of seven days.

Research activities
The long-term goal of the research in our department is to determine the molecular events that lead tothe development of Alzheimer's disease (AD).

Current goals include:
1 Characterization of γ-secretase—Senile plaques, oneof the neuropathological hallmarks of Alzheimer’s
disease (AD), are composed of a small ~40-residue
protein called amyloid β-protein (Aβ). Aβ is produced
from β-amyloid precursor protein (APP), through sequential cleavages by two membrane proteases referred to as β- and γ-secretases. β-Secretase is amembrane-bound aspartyl protease, and cleaves APP
in its luminal portion, generating a 99-residue-

69

fragment called βC-terminal fragment (βCTF). βCTF
in turn is cleaved by γ-secretase in the middle of its
transmembrane domain, generating Aβ which is finally secreted into the extracellular space. While themost predominant product is Aβ40, a two-residue
longer species, Aβ42, is believed to be the species
initially deposited in the brain and predominates insenile plaques. Thus far, three causative genes for familial AD, APP, presenilin (PS) 1, and PS2, have been
identified, and the FAD mutations found in thesegenes lead to increased production of Aβ42, strongly
suggesting that Aβ42 is a real culprit for AD.
The mechanism of intramembrane cleavages at theAβ40 and Aβ42 sites by γ-secretase has remained an
enigma. Accumulating evidence suggests that γ-secretaseis also an aspartyl protease with its catalytic site(s)sitting within the membrane. Active γ-secretase is assumed to take the form of a high-molecular-weightmultiprotein complex consisting of at least four integral membrane proteins, PS, Aph-1, nicastrin, and
Pen-2, all of which are essential for the emergence offull γ-secretase activity. PS1/2 appear to compose thecatalytic core of γ-secretase.
γ-Secretase cleaves APP in the middle of the transmembrane domain (γ-cleavage), releasing Aβ, andnear the membrane-cytoplasm boundary (ε-cleavage),
producing APP intracellular domain (AICD).
ε-Cleavage generates AICD50-99, a major product,and AICD49- 99, a minor product. Although the relationship between γ- and ε-cleavages is still not wellunderstood, our previous study showed that somecorrelations exist between the major counterparts,
Aβ40 vs. AICD50-99, and between the minor counterparts, Aβ42 vs. AICD49- 99.
We have identified several longer Aβs within cells
and in the brain, including Aβ43, Aβ45, Aβ46, andAβ48. In contrast, only two species of AICD49-99 and50-99 were identified in the newly established solubilized assay system. Thus, it is likely that βCTF undergoes first ε-cleavage, followed by γ-cleavages atmultiple sites within its transmemebrane domain.
These cleavage sites are aligned on the α-helical surface of the transmembrane domain, and we speculatethat βCTF is processed at every third residue from its
C-terminus by γ-secretase.
2 Tau and neuronal cell deathMicrotubule-binding protein tau, which promotes
tubulin polymerization and stabilizes microtubules,
was identified as the major component of the framework of neurofibrillary tangles (NFT) found in thebrain affected by so called tauopathy, the conditions
such as Alzheimer’s disease (AD) and frontotemporaldementia with parkinsonism linked to chromosome 17(FTDP-17). Patients affected by FTDP-17 develop
execution problems, behavioral abnormalities, often
parkinsonism, and finally dementia. More than 25
exonic and intronic mutations in the tau gene in
FTDP-17 families are currently found, strongly suggesting that tau is directly involved in the neurodegeneration and neuronal loss.
Those animal models so far made provide both invaluable information about the nature of neurodegeneration caused by tauopathy. However, detailed pictures of neurodegeneration have remained unknown
largely because of the complexity of the nervous system. We thus generated transgenic nematode expressing human WT tau or two kinds of FTDP-17 mutanttau (P301L and R406W) in six mechanosensory neurons, ALML/R, AVM, PLML/R, and PVM. They canbe readily traced to their fine neuronal processes under microscopy, a condition which is difficult to obtain in other models. These neurons are characterized
by distinct microtubules of a larger diameter that consist of 15 protofilaments (instead of 11), and by expression of MEC-12 and MEC-7, and distinct types ofα and β-tubulin.
Decreases in the touch response are associated withvarious types of neuritic abnormalities. The greater
these alterations are, the more the response is decreased. Various abnormal neuritic characteristics
could be interpreted as derived from generation ofaberrant neurites during development. These observations would suggest that dysfunction, a decrease in thetouch response, is not due to neuronal loss, but may be
due to the formation of abnormally generated neurites,
presumably leading to the formation of abnormal
neuronal circuits and resulting in null response. Thereappear to be two types of neurodegeneration, tauaccumulating and tau-nonaccumulating degeneration,in the affected worms. This view was previously proposed for the neocortical neurons affected by AD,
based on unbiased stereological observations. Even if
tau does not accumulate in the cell bodies, their neu-

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ronal processes are already abnormal, suggesting thateven a trace amount of tau, especially of mutant tau,can be toxic to touch neurons. We do not currently
know why these two types of neurodegeneration canhappen. One possibility would be that tau accumulation is a late event during the course of neurodegeneration, and the rate of accumulation varies for individual cells. In rapidly degenerating neurons, tau may
not be produced sufficiently to accumulate, leading totau-negative degeneration. In contrast, in slowly degenerating neurons, tau exists in sufficient amounts toaccumulate, leading to tau-positive degeneration. Thisstrongly suggests that tau accumulation (or formationof tau inclusions) is not required for the toxic effect ofmutant tau.

References
1. Yagishita S, Morishima-Kawashima M, Tanimura
Y, Ishiura S, Ihara Y: DAPT-induced intracellularaccumulations of longer amyloid βproteins: further implications for the mechanism of intramembrane cleavage by γ-secretase. Biochemistry 45:3952 -3960, 2006
2. Kuwano R, Miyashita A, Arai H, Asada T, Imagawa M, Shoji M, Higuchi S, Urakami K, Kakita
A, Takahashi H, Tsukie T, Toyabe S, Akazawa K,
Kanazawa I, Ihara Y; Japanese Genetic Study
Consortium for Alzeheimer's Disease. Dynaminbinding protein gene on chromosome 10q is associated with late-onset Alzheimer's disease. Hum
Mol Genet. 15:2170-2178, 2006
3. Kakuda N, Funamoto S, Yagishita S, Takami M,
Osawa S, Dohmae N, Ihara Y. Equimolar production of amyloid β-protein and amyloid precursor
protein intracellular domain from β-carboxylterminal fragment by γ-secretase. J Biol Chem
281:14776-14786, 2006

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Department of Neurochemistry
Associate Professor and Head
Haruhiko Bito, M.D., Ph.D.

Assistant Professors
Hiroyuki Okuno, Ph.D.
Sayaka Takemoto-Kimura, M.D., Ph.D.

Homepage

http://www.neurochem.m.u-tokyo.ac.jp/Homepage.html

Introduction and Organization
Our Department’s primary goal is to elucidate thebasic signal transduction mechanisms which mediate
key processes underlying various brain functions, suchas learning, memory or emotion. A fundamental question is how an ensemble behavior of 10~100 billion
neurons can possibly give rise to a coherent and integrated “brain” that controls the whole human organism for a period of more than eighty years. Our central
nervous system is physically wired and organizedbased on evolutionary and developmental principles
that are primarily encoded into the genome and thatare highly conserved in mammals from rodents toprimates. This neural network, however, is able torecognize and memorize external and internal eventsas they occur. And furthermore, brain function, especially human’s, stands out by its intrinsic capacity
to extract patterns and rules from these events, and to
consciously associate them with abstract meaning andaffective valence, while also unconsciously facilitating coordinated body responses.
Neurochemistry once used to be a relatively dull
discipline consisting of analyzing substances that form
the brain. However, it has recently become a field of
excitement where we are now (almost) able to measure changes in cellular messengers or modifications insignaling molecules in critical parts of the neurons
such as the dendritic spines or the axon terminals, as
the neurons summate synaptic potentials or fire action
potentials.
What are the precise nature and the whole spectrumof the molecular changes in the neurons that undergo
heavy or patterned electrical activity? What are themolecular rules that govern these local and globalchanges, both electrical and chemical? How are these
events, in turn, converted into more profound modifications of the synaptic wiring mechanisms? And finally do these alterations genuinely underlie certain
kinds of information processing and storage?
To address these issues, this Department currently
focuses its resources into two basic aims:
1) Molecular investigation (including identification,
characterization and real-time visualization) of
signaling molecules involved in calciumdependent synaptic modification, especially during
signaling from synapse-to-nucleus, and back from
nucleus-to-synapses.
2) Understanding molecular mechanisms controlling
cytoskeletal dynamics and remodeling on bothsides of the synapses, in the dendritic spines and inaxon terminals.
Following the retirement of Professor Tatsuya Haga
(who became the President of Life Sciences Instituteat the Faculty of Science at Gakushuin Univisersity)
in March 2001, and the departure of Associate Professor David Saffen to initially University of Minnesota and then to Ohio State University in August 2001,
Associate Professor Haruhiko Bito was appointed as
Head of Department since January 2003. The Department is located on the 6th floor, in the West wing of
the third building of the Medical School. The Department currently enrolls one associate professor, two
assistant professors, two postdoctoral scholars, one

72technical staff member, two Ph.D. and two M.S.-Ph.D.
graduate students, three rotating medical students,
three technical assistants and one administrative assistant.

Teaching activities
The Department’s teaching activities include:
1) Introductory Neuroscience coursework provided to
pre-medical students in the Komaba campus (onehour);
2) Neurochemistry lectures to medical students aspart of the “Biochemistry- Molecular BiologyNutrition” core curriculum (two hours);3) Introductory Molecular and Cellular Neuroscience,
and Basic Neurochemistry lectures to first-year
master degree students (three hours);
4) Organization of the lecture course: “Basic Neuroscience” (Molecular and Cellular Neuroscience) (alecture series with fifteen lectures from outstanding neuroscientists from all over Japan).
Additionally, Neurochemistry Seminars are frequently and regularly organized under the auspices ofthe 21st Century Center of Excellence Program Grant“Center for Integrated Brain Medical Science”. This
enables direct exposure of Ph.D. graduate students andpostdocs to both young promising researchers andestablished investigators from all over the world.

Research activities
The Department of Neurochemistry currently focuses its resources into two core projects:
1) Molecular investigation (including identification,
characterization and real-time visualization) of
signaling
molecules
involvedincalcium-dependent synaptic modification, especiallyduring signaling from synapse-to-nucleus, andback from nucleus-to-synapses.
Changes in efficacy of synaptic transmission havebeen shown to strongly correlate with functional plasticity of many brain circuits including the hippocampus, the amygdala, the striatum, the neocortex, thecerebellum or the spinal cord. An early phase of longterm synaptic plasticity is induced by virtue of spe-cific post- and/or presynaptic modifications of thebiochemical machinery dedicated to synaptic releaseand neurotransmitter recognition. It then is expressedby bistable mechanisms that are strongly governedand dictated by the pattern of synaptic calcium influxes experienced during the initial conditioning period. While the molecular identity of the involved
synaptic proteins is now (almost) being solved (or is
becoming much less controversial than before), several essential questions remain unanswered.
The “Old” question was: What are the moleculardeterminants that enable these plastic changes to be
induced and maintained locally?
Yet, related issues of critical importance that still remain wide open questions are:1) What are the full-range of calcium-triggered molecular signaling cascades which are activated atand near the potentiated/depressed synapses? And
how do they influence plasticity per se?
2) What is the contribution of activity-dependent
gene expression in prolongation and consolidationof such synapse-restricted changes?
In order to begin to address these issues, we havebeen investigating in particular the role of several calcium-calmodulin dependent protein kinases.
We previously showed the critical importance of a
CaMKK/CaMKIV cascade in triggering synaptically-stimulated nuclear CREB phosphorylation in
hippocampal neurons. The extreme biochemical efficacy and the relative poor frequency-dependence of
this signaling cascade, in combination with the robust
correlation between prolonged pCREB response anddownstream gene expression led us to propose that
CaMKK/CaMKIV/pCREB cascade was likely to act
as a critical temporal integrator for activity-dependent
gene expression in excitatory neurons (Bito et al., Cell,
1996; Bito et al., Curr. Opin. Neurobiol., 1997; Bito,
Cell Calcium, 1998). This hypothesis has now been
critically tested in various brain systems and indeed
pCREB immunofluorescence is now considered as auniversal marker for integrated synaptic activity thatis more sensitive than that of c-Fos. Furthermore,
CaMKIV-KO, CaMKK-KO and CaMKIV-dominantnegative transgenic studies by many laboratories haveconfirmed the critical role for CaMKIV as synaptic
activity-triggered CREB kinase.
We subsequently also showed that CaMKIV in the

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cerebellar granule cells played a critical role in tuning
the pCREB response necessary for depolarization-mediated neuronal survival, and that in fact
CaMKIV stability was actively maintained by depolarization. Loss of depolarizing signal led to a caspase-mediated proteolytic degradation of CaMKIV.
This in turn severely impaired CREB phosphorylation,
facilitating apoptosis, and conversely rescuing pCREB
by overexpressing an active form of CaMKIV was
sufficient to prevent apoptosis (See et al., FASEB J.,
2001). Consistent with our observation that subtle
CREB regulation may underlie the neuronal cell survival, CREB-dependent gene expression mechanisms,
especially CBP regulation, have actually been proposed to be affected in one way or another in manyneurodegenerative disorders such as hereditary polyglutamine diseases. We thus speculated that if
CREB-opathies (or various defects in CREB-mediatedgene activation mechanisms) were critical determinants in exacerbating neurodegeneration, certain disease forms may actually accompany deficit in CaMKIV / pCREB signaling (Bito and Takemoto-Kimura,
Cell Calcium 2003). This hypothesis is now being
tested.
One parallel branch of CaMK signaling that has notbeen widely studied is the CaMKK/CaMKI pathway.
During the search for potential CaMKIV-like CREB
regulatory kinases (CLICKs) (Ohmae et al., J. Biol.
Chem. 2006; Fuse et al. in press), we identified anovel CaMKI isoform that contained a C-terminal
CAAX lipid modification motif (Takemoto-Kimura etal., J. Biol. Chem., 2003). This novel membrane-bound CaMK (CLICK-III/CaMKIγ) is mostexpressed in the central nucleus of the amygdala andin the ventral medial hypothalamus, while also being
present at a much weaker amount in most central
neurons. Ongoing biochemical and cell biologicalstudies indicate a critical role for lipidification of thiskinase to be properly sorted into specificlipid-restricted membrane microdomains. The function played by this lipidified, membrane-inserted
CaMK in circuitry formation and maturation was
scrutinized using RNA interference. Along with theidentification of the critical lipid-modifying enzymethat controls lipid-anchoring of this kinase, we discovered a novel activity-regulated mechanism whererby CLICK-III/CaMKIγ is actively sorted into den-dritic lipid rafts, where it specifically regulates
Rac-mediated actin remodeling that is required for
BDNF-stimulated dendritogenesis (Takemoto- Kimura,
Ageta-Ishihara et al., Neuron, 2007).
One further important topic that we have been focusing for a number of years is the role of gene expression in prolongation / consolidation of synapse-specific local changes. Neurons undergoing
various stimulus patterns have been followed up intime and the amount of newly synthesized proteins
and the local distribution of induced gene products
have been monitored. Using state-of-the-art multiwavelength fluorescence imaging techniques, we are
now quantitatively assessing how local distribution ofthese newly synthesized gene products affect synaptic
protein complexes (Okuno and Bito, AfCS/Nature
Mol. Pages, 2006).
2) Understanding molecular mechanisms controlling
cytoskeletal dynamics and remodeling on bothsides of the synapses, in the dendritic spines and inaxon terminals.
Both synaptic maturation and synaptic plasticity
have been shown to include a morphological component that is directed by the dynamics of actin cytoskeleton, a major cytoskeletal component both in thedendritic spines and at the very proximity of boutons
in the axon terminals. Few studies in the past, however,had directly addressed what molecular determinants
regulate actin dynamics in living central neurons undergoing synaptic activity. This was in part because
actin filament assembly and disassembly were classically studied mostly at the moving edges of lamellipodia of large growth cones in large-size neurons fromeither mollusc or peripheral nerve cells. Such visualization turned out to be much more difficult in seemingly far less mobile spine structures tightly apposed
to presynaptic active zones.
We (and others) used GFP-actin imaging to try tounderstand how neuronal actin cytoskeleton in hippocampal neurons was organized and reorganized byexposure to synaptic activity. In our dissociated culture system, virtually all spines contained a highamount of GFP-actin and most of them with few exceptions were apposed to FM4-64-positive active
presynaptic termini. In these cultures, increases in74synaptic glutamatergic transmission by repeated burstsof high-frequency synaptic activity clearly induced
several distinct kinds of activity-dependent actin mobilization, including a slow but sustained synaptic
delivery of GFP-actin in a non-negligible number ofactivated spines and a massive but transient enhancement in cortical actin at the somatic periphery. The
former was entirely dependent on NMDA-dependent
Ca2+-influx while the latter was likely to be mediatedat least in part by L-type voltage-gated Ca2+ channel
activity. Thus distinct patterns and sources of Ca2+
influx were likely to trigger a complex spatiallysegretated patterns of actin cytoskeletal reorganization,with variable impact on either neuronal morphology
and/or synaptic protein assembly (Furuyashiki et al.,
PNAS, 2002).
Similar studies are now ongoing in cerebellar Purkinje neurons, where spinogenesis is also subject tocomplex regulation during development, and where
calcium dynamics is key to pre- and postsynaptic
plasticity.
What are the key signaling pathways controlling
actin dynamics in central neurons? We were especiallykeen to resolve the contribution of the small GTPase
Rho and its downstream effectors, initially in the context of developmentally regulated neuronal morphogenesis. We first established in a model cell line
N1E-115 that neurite retraction was directly linked to
Rho/ROCK activity (Hirose et al., J. Cell Biol., 1998).
We subsequently revealed that in central neurons, inaddition to its essential role in regulating growth cone
motility, Rho/ROCK activity in fact acted as a negative gate that tightly controls the timing with which
the first processes are initiated out from the round cellsoma (Bito et al., Neuron, 2000). Disruption of
Rho/ROCK activity was sufficient to immediately
initiate neuritogenesis. This indicated that endogenous
Rho activators, by titrating ROCK activity, continuously antagonized process/ branch formation and that
local gradient of Rho activators might play a crucialrole in shaping the timing and the extent of process
formation (Bito, J. Biochem., 2003). Consistent withthis idea, we found that in cerebellar granule cells, achemokine SDF-1α released from the pia mater was
likely to be a predominant Rho activator via stimulation of a cognate and specific GPCR CXCR4 (Arakawa et al., J. Cell Biol., 2003). While a true gradientin SDF-1α still remains to be demonstrated in vivo, it
is intriguing to note that most active axonal process
formation and elongation actually occur in the innerzone of EGL that is opposite and most distant from theinterface with the pia mater (Bito, J. Biochem., 2003).
Most strikingly, we demonstrated that axon elongation
could actively occur in an intermediate Rho activity
range that enables ROCK to be weakened enoughwhile allowing another Rho effector mDia1 to actively
mediate its effect on actin nucleation and polymerization (Arakawa et al., J. Cell Biol., 2003; Yamana et al.,Mol. Cell Biol. 2006).
Whether similar or distinct mechanisms also operate during spinogenesis and spine maturation remains
to be determined, though a role for Rho and ROCK
has already been postulated in control of spine complexity and spine stability. However, multiple small
GTPase signaling cascades clearly seem to contribute
together, in a tightly coordinated manner, to spine
regulation, since many distinct classes of GEFs and
GAPs have now been shown to be localized in thedendritic spines. We ourselves initially reported thefirst two direct examples for PSD localization for such
Rho small GTPases interacting proteins, Citron (Furuyashiki et al., J. Neurosci., 1999) and Cupidin/
Homer2 (Shiraishi et al., J. Neurosci., 1999).
In an attempt to pin down molecular mechanismsthat link PSD complexes and spine formation, wequantitatively examined the effect of deleting thebinding capacity of single PDZ domains of PSD-95,
one by one, and in combination, by structure-based
amino acid replacements rather than domain deletion.
Such a second-generation structure-function relation
study surprisingly revealed that a quantitative binding
between PSD-95 and synGAP tighly controlled thedegree of PSD protein clustering in a manner that was
inversely correlated with the distance from the spine
head to the shaft. Thus, these results suggest the existence of a tight coordination between the state of PSD
complex and the morphogenetic activity of each spine(Nonaka et al. J. Neurosci., 2006).
In parallel with this work, we and others determinedthat protein-protein interaction was key to determining
the physical distance between the synaptic vesicles in
the active zone and the voltage-gated calcium channels in its vicinity, the opening of which triggers theirrelease (Kiyonaka et al., Nature Neurosci., 2007).

75

Publications by lab members(April 2006 - March 2007)
1. Ohmae S, Takemoto-Kimura S, Okamura M, Adachi-Morishima A, Nonaka M, Fuse T, Kida S,
Tanji M, Furuyashiki T, Arakawa Y, Narumiya S,
Okuno H, Bito H. Molecular identification andcharacterization of a family of kinases with homology to Ca2+/calmodulin-dependent protein
kinases I/IV. J. Biol. Chem. 281: 20427-20439,
2006.
2. Uemura K, Kihara T, Kuzuya A, Okawa K, Nishimoto T, Bito H, Ninomiya H, Sugimoto H, Kinoshita A, Shimohama S. Activity-dependent
regulation of β-catenin via ε-cleavage ofN-cadherin. Biochem Biophys Res Commun.
345: 951-958, 2006
3. Kuriu T, Inoue A, Bito H, Sobue K, Okabe S.
Differential control of postsynaptic density scaffolds via actin-dependent and independent
mechanisms. J. Neurosci. 26: 7693-7706, 2006.
4. Yamana N, Arakawa Y, Nishino T, Kurokawa K,
Tanji M, Itoh RE, Monypenny J, Ishizaki T, Bito
H, Nozaki K, Hashimoto K, Matsuda M, Narumiya S. Rho-mDia1 pathway regulates cell polarity and focal adhesion turnover in migrating cells
through mobilizing APC and c-Src. Mol. Cell
Biol. 26: 6844-6858, 2006.
5. Sato K, Suematsu A, Nakashima T, Takemoto-Kimura S, Aoki K, Morishita Y, Asahara H,
Ohya K, Yamaguchi A, Takai T, Kodama T,
Chatila TA, Bito H, Takayanagi H. Regulation of
osteoclast differentiation and function by the
CaMK-CREB pathway. Nature Med. 12: 1410 1416, 2006.
6. Kiyonaka S, Wakamori M, Miki T, Uriu Y,
Nonaka M, Bito H, Beedle AM, Mori E, Hara Y,
De Waard M, Kanagawa M, Itakura M, Takahashi
M, Campbell KP, Mori Y. The active zone protein
RIM1 confers sustained activity and neurotransmitter vesicle anchoring to presynaptic Ca2+
channels. Nature Neurosci., 10: 691-701, 2007.
7. Takemoto-Kimura S, Ageta-Ishihara N, Nonaka M,
Adachi-Morishima A, Mano T, Okamura M, Fujii
H, Fuse T, Hoshino M, Suzuki S, M Kojima,
Mishina M, Okuno H, Bito H. Regulation of den-dritogenesis via a lipid raft-associated Ca2+/
calmodulin-dependent protein kinase CLICK-III/
CaMKIγ. Neuron, 54: 755-770, 2007.

78

Department of Speech Science
Associate Professor
Yoshihiro Takayama, M.D.

AssociateKenji Itoh, Ph.D.,

Michiru Makuuchi, Ph.D.

Homepage
Introduction and Organization

Research activities

Speech and language are the most prominent cognitive functions distinguishing human being from nonhuman animals. The Department of Speech Scienceaims at basic, interdisciplinary studies on the humanspeech and language communication. The researcharea ranges from physical and physiological processesin speech production and perception, developmental
as well as adult cognitive processes in speech andnonverbal communication to medical application of
speech and hearing support technologies. Many studies are conducted in cooperation with other departments, faculties and universities such as in the field ofengineering, linguistics, psychology, education andclinical neuroscience.

1. Brain mechanisms on spoken language production,
comprehension and their linkage in human communication
2. Physical, physiological and computational modeling studies on verbal and nonverbal temporal
behaviors of Japanese and others
3. Cognitive process in acquisition of native speech,
language and communication skills in infants andchildren
4. Learning mechanisms of second language andworld knowledge in adults with established first
language
5. Objective and quantitative assessment of normal
as well as pathological speech, language and social skills
6. Technological and computational developments ofaids for the hearing, speech, language and mentally handicapped

Teaching activities
1. Graduate Course
Speech Science and Language Communication
Pathophysiology of Higher Brain Functions(for School of Humanities and Sociology)
2. Undergraduate Course
Introduction to Medical Data
Speech and Language Communication* The lectures are conducted in collaboration with the
Departments of Speech Physiology and Sensory andMotor Neuroscience.

References
1. Itoh K, Uetsuki M, Iwanami A, Mazuka R, Kikkawa S, Niwa S, Kaga K. High-density EEG coherence in multiple event-related oscillations andpotentials during linguistic process. Clin Neurophysiol. 2006;117:S178.
2. Karino S, Yumoto M, Itoh K, Uno A, Yamakawa
K, Sekimoto S, Kaga K. Neuromagnetic responses
to binaural beat in human cerebral cortex,J Neurophysiol. 2006;096:1927-38.
3. Kawakubo Y, Kasai K, Kudo N, Rogers MA,

79

4.

5.

6.

7.

Nakagome K, Itoh K, Kato N. Phonetic mismatch
negativity predicts verbal memory deficits inschizophrenia. NeuroReport. 2006;17:1043-6.
Kudo N, Kasai K, Itoh K, Koshida I, Yumoto M,
Kato M, Kamio S, Araki T, Nakagome K, Fukuda
M, Yamasue H, Yamada H, Abe O, Kato N, Iwanami A. Comparison between mismatch negativity
amplitude and magnetic mismatch field strength
in normal adults. Biol Psychol. 2006;71:54-62.
Ogata E, Yumoto M, Itoh K, Sekimoto S, Karino
S, Kaga K. A magnetoencephalographic study ofJapanese vowel processing. Neuroreport. 2006;17:1127-31.
Yamakawa K, Itoh K, Yumoto M, Karino S, Kaga
K. Magnetoencephalographic study on reading
direction of Japanese. Clin Neurophysiol. 2006;
117:S136-7.
Yumoto M, Itoh K, Karino S, Ogata E, Mizuoch T,
Yatomi Y. A motor-to-sound oddball paradigm
revealed top-down modulation of auditory perception in a multimodal predictive context. Clin
Neurophysiol. 2006;117:S135.

* Takayama Y, Makuuchi M. See References in
Department of Speech Physiology

82

Department of Neuropsychiatry
Professor
Nobumasa Kato, M.D., Ph.D.

Associate Professor
Nobuo Nakayasu, M.D., Ph.D.,

Koichi Tsunashima, M.D., Ph.D.

Lecturer
Masatoshi Shibayama, M.D., Ph.D.,

Kiyoto Kasai, M.D., Ph.D.,

KeiIchiro Watanabe, M.D., Ph.D.

Associate
Mamoru Tochigi, M.D., Ph.D.,

Toshiyuki Otani, M.D., Ph.D.,

Hitoshi Kuwabara, M.D., Ph.D.,

Yuka Obi, M.D.,

Hidenori Yamasue, M.D., Ph.D.,

Tsuyoshi Araki, M.D.,

Kenji Otowa, M.D., Ph.D.,

Soo-Yung Kim, M.D., Ph.D.,

Tsuyoshi Okamura, M.D.,

Jiro Asahina, M.D.

Homepage

http://npsy.umin.ac.jp/

Introduction and Organization

Clinical activities

The Department of Neuropsychiatry is Japan's oldest psychiatric department which was established in
1886. "Anti-Psychiatry" movement for the last 3 decades had highly negative effects on the progress in all
aspects of our activities. However, since 1994, ourdepartment has been normalized and restarted to playa leading role in psychiatry in Japan. Now the Department of Neuropsychiatry provides a wide-ranged
clinical, training, and research services. Since August
2006, we have been working in the new closed ward
(30 beds) and in the open ward (30 beds). Moreover,since 2000, we have been supported by a government
grant for basic and clinical neuroscience instress-related disorders including posttraumatic stressdisorder (PTSD). Since 2005, we have begun to focus
on basic and clinical neuroscience in pervasive developmental disorders (PDDs).

For outpatient services, we have more than 20 staff
psychiatrists, 4 clinical psychologists, 2 trained nurses,
and 1 psychiatric social worker. Approximately 1200
new patients visited yearly (2005), and the total visits
per year was about 35,000 (140 per day).
The secluded ward has 29 beds including 3 seclusion rooms. We also have 31 beds for the open generalward. Approximately 350 patients with various psychiatric disorders were admitted in a year (2005),
about one-third of whom were referred from theemergency unit. Occupational therapy, recreational
therapy, group therapy, and art therapy are performed.
We established Japan’s first child psychiatry day
care unit in national university hospitals in 1967. Aschildren with Down’s syndrome began to be accepted
into nurseries and kindergartens around the year 1975,
the focus of this division shifted to the psychologicalpedagogy of autism. Treatment of autism changed
along with the understanding of the clinical condition,

83

from behavioral therapy to cognitive development
based therapy. Since 1997, our division was reducedin size and an improved therapy system, “developmental psychology outpatient clinic” was established.
This outpatient clinic encompasses individual treatment and psychological counseling by clinical psychologists under the supervision of psychiatrists. Our
staff includes 1 full-time psychiatrists, 4 part-time
psychiatrists, and 3 clinical psychologists. We provide
care for 260 autistic or developmentally disabledchildren per year. Since 2000, a short term therapy
group program has started. Parents participated in thetreatment program alongside the staff members. Thisnot only emphasizes the therapy of the child, but assesses their developmental level from many directions.
The purpose of the therapy program is to help parents
gain a better understanding of children’s disability andto help them to acquire a more supportive role for
their children in the home environment. Since 2005,
we have established clinical and educational center for
developmental disorders, and provided clinical andeducational activities in pervasive developmental disorders.

Teaching activities
For psychiatric residents, we have provided: 1)
clinical meetings on patients (every morning); caseconferences on inpatients (every week); 3) a series oflectures by teaching staffs on various aspects of psychiatry. For undergraduates, we have provided neuropsychiatry comprehensive lectures (2nd year), bedsidelearning (3rd year), and clinical clerkship (elective for
4th-year students). For postgraduate, currently morethan 20 neuropsychiatry Ph.D. students are studying.

Research activities
Stress- It is well accepted that neuropeptide Y(NPY) is involved in anxiolytic-like effects and anti-stress effects. Pharmacological and behavioral studies have consistently indicated that these effects aremainly mediated through an activation of NPY Y1
receptor in the brain. To further elucidate the functional role of Y1 receptor, we have evaluated the histological and behavioral changes in Y1 receptor-deficient mice, after an exposure to 2h of restraint

stress. Trimethyltin (TMT), a neurotoxic organotin,
has been shown to cause selective loss of pyramidal
neurons in the rat hippocampus, similar tostress-induced hippocampal changes. Several recent
studies in animal models of brain ischemia revealed
the neuroprotective properties of tacrolimus (FK506),
a potent immunosuppressant used in organ transplants.
Therefore, we have investigated the effect of FK-506
on the neuronal death and apoptosis in the hippocampus after TMT intoxication, using immunohistochemistry and TUNEL method.
Epilepsy- Systemic injection of kainic acid in rat
causes severe convulsions, increased seizure susceptibility and seizure-induced neuronal death. Since precise mechanisms of various anticonvulsants are still
unclear, we have investigated to elucidate whether
these anticonvulsants demonstrate neuroprotective
effects on kainic acid-induced neuronal death in the
hippocampus.
Environmental endocrine disrupter- Bisphenol-A(BPA), one of environmental endocrine disrupters, isreleased from polycarbonate plastics, and is known to
mimic oestrogens in their action. Recent studies reported that prenatal and neonatal exposure to low-dose
bisphenol-A modulates the sexual differentiation of
behavior and the central dopaminargic effects in vivo
and in vitro. We examine the effects of BPA on the
behavior, memory and the expression of estrogen-alpha receptor in the brain of rats exposed to BPA
during the fetal and suckling periods at a dosage farless than the no-observed-adverse-effect level.
Genetic Research- The Genetic Research Group of
the department is investigating genetic as well as environmental mechanism of psychiatric disorders. A
major focus of the studies is exploration of susceptibility genes of the disorders including schizophrenia,
infantile autism, their spectrum disorders and anxiety
disorder (mainly panic disorder). A number of candidates of the susceptible genes are studied usingcase-control and TDT (transmission disequilibriumtest) designs. We are at present achieving most interesting results in the investigations of DISC1, Neuregulin1 and other candidate genes in schizophrenia andthe chromosome 7 genes in infantile autism. Anotherfocus is investigation of genes that affect the development of personality.
Neuroimaging- Our group plays a leading role in

84

psychiatric neuroimaging in Japan. Our research aims
at multi-modality neuroimaging (structural and functional MRI, MR spectroscopy, EEG, MEG, nearinfrared spectroscopy (NIRS), PET) in schizophrenia,
mood disorders, pervasive developmental disorders,and posttraumatic stress disorder (PTSD).
Clinical Pharmacology- The atypical neuroleptics
have been widely prescribed in our country. They
contribute to the reduction of uncomfortable side effects and the improvement of the patient’s QOL. But
the typical neuroleptics still have been used becauseof their sedative effects particularly in acute state of
Schizophrenia. We have been investigating a voluntary clinical research, which contain the practicalevaluation to the treatment of atypical neuroleptics for
acute psychotic state in Schizophrenia.
Recently the abnormal glucose tolerance induced byatypical neuroleptics had been reported and some accidental hyperglycemia had happened in our country,
too. Though there are many reports involving to thisproblem in foreign country, few detailed investigation
was performed in Japan until now. We are preparing to
examine the glucose tolerance of inpatients that aretreated by neuroleptics in collaboration with many
hospitals and expect that the frequency of risk andsome actual factors will be revealed.
Neuropathological study of dementias- Our interestis neuropathological background of dementia, especially NFT-predominant form of dementia (NFTD).
NFTD is a sporadic subset of dementia pathologicallycharacterized by abundant and almost exclusive appearance of NFTs in the limbic areas with scarcity ofsenile plaques. Our study suggests that pathogenetic
background of NFTD may be different from that of
AD and cognitive decline in NFT-SC may be affected
not only by severity of NFT pathology but also bycoexisting vascular lesions and/or argyrophilic grains.

References
1

2

Abe O, Yamasue H, Aoki S, Suga M, Yamada H,
Kasai K, Masutani Y, Kato N, Kato N, Ohtomo K:
Aging in the CNS: comparison of gray/whitematter volume and diffusion tensor data. Neurobiol Aging, in press.
Abe O, Yamasue H, Kasai K, Yamada H, Aoki S,
Iwanami A, Ohtani T, Masutani Y, Kato N, Oh-

tomo K: Voxel-based diffusion tensor analysis reveals aberrant anterior cingulum integrity in posttraumatic stress disorder due to terrorism. Psychiatry Res Neuroimaging 146: 231-242, 2006
3 Araki T, Yamasue H, Sumiyoshi T, Kuwabara H,
Suga M, Iwanami A, Kato N, Kasai K: Perospirone in the treatment of schizophrenia: effect on
verbal memory organization. Prog Neuropsychopharmacol Biol Psychiatry 30: 204-208, 2006
4 Araki T, Kasai K, Rogers MA, Kato N, Iwanami
A: The effect of perospirone on auditory P300 in
schizophrenia: a preliminary study. Prog Neuropsychopharmacol Biol Psychiatry 30: 1083-1090,
2006
5 Araki T, Kasai K, Kirihara K, Yamasue H, Kato N,
Kudo N, Nakagome K, Iwanami A: Auditory P300
latency prolongation with age in schizophrenia:
gender and subcomponent effects. Schizophr Res
88: 217-221, 2006
6 Ebisawa T: Circadian rhythms in the CNS andperipheral clock disorders: Human sleep disorders
and clock genes. J Pharmacol Sci, in press
7 Fujimura Y, Ikoma Y, Yasuno F, Suhara T, Ota M,
Matsumoto R, Nozaki S, Takano A, Kosaka J,
Zhang M.-R, Nakao R, Suzuki K, Kato N, Ito H:
Quantitative analyses of [18F]FEDAA1106 binding to peripheral benzodiazepine receptors in living human brain. Journal of Nuclear Medicine 47:
43-50, 2006
8 Hibino H, Tochigi M, Otowa T, Kato N, Sasaki T:
No association of DRD2, DRD3, and tyrosine hydroxylase gene polymorphisms with personality
traits in the Japanese population. Behav Brain
Funct 2: 32, 2006
9 Ikoma Y, Yasuno F, Ito H, Suhara T, Ota M, Toyama H, Fujimura Y, Takano A, Maeda J, Zhang
M.-R, Nakao R, Suzuki K: Quantitative analysis
for estimating binding potential of the peripheral
benzodiazepine receptor with [11C]DAA1106. J
Cereb Blood Flow Metab: Published online, inpress
10 Kaneko N. Kudo K. Mabuchi T. Takemoto K.
Fujimaki K. Wati H. Iguchi, H. Tezuka H, Kanba
S: Suppression of cell proliferation by interferonalpha through interleukin-1 production in adult rat
dentategyrus.
Neuropsychopharmacology
advance online publication, in press

85

11 Kato N, Sadamatsu M, Taeko K, Noriko N, Fukuyama Y: Paroxysmal Knesigenic Choreoathetosis: From first discovery in 1892 to genetic linkage with benign familial infantile convulsions.
Epilepsy Research 70S: S174-S184, 2006
12 Kawakubo Y, Kasai K, Rogers MA, Nakagome K,
Iwanami A, Kamio S, Nose T, Kato N, Fukuda M:
Phonetic mismatch negativity predicts social skills
acquisition in schizophrenia. Psychiatry Res, inpress.
13 Kawakubo Y, Kasai K: Support for an association
between mismatch negativity and social functioning in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 30: 1367-1368, 2006
14 Kawakubo Y, Rogers MA, Kasai K: Procedural
memory predicts social skills in persons withschizophrenia. J Nerv Ment Dis 194: 625-627,
2006
15 Kawakubo Y, Kasai K, Kudo N, Rogers MA, Nakagome K, Itoh K, Kato N: Phonetic mismatch
negativity predicts verbal memory deficits inschizophrenia. Neuroreport 17: 1043-1046, 2006
16 Kawashima M, Tamiya G, Oka A, Hohjoh H, JujiT, Ebisawa T, Honda Y, Inoko H, Tokunaga K:
Genomewide association analysis of human narcolepsy and a new resistance gene. Am J Hum
Genet 79: 252-263, 2006
17 Kazuno A, Munakata K, Nagai T, Shimozono S,
Tanaka M, Yoneda M, Kato N, Miyawaki A, Kato
T: Identification of mitochondrial DNA polymorphisms that alter mitochondrial matrix pH and intracellular calcium dynamics. PLoS Genetics, inpress
18 Kikuchi T, Nomura M, Tomita H, Harada N, Kanai K, Konishi T, Yasuda A, Matsuura M, Kato N,
Yoshiura K, Niikawa N: Paroxysmal kinesigenic
choreoathetosis (PKC): Confirmation of linkage
to 16p11-q21 but unsuccessful detection of mutations among 157 genes at the PKC-critical regionin seven PKC families. J Hum Genet, in press
19 Kohda K, Jinde S, Iwamoto K, Bundo M, Kato N,
Kato T: Maternal separation stress drastically decreases expression of transthyretin in the brains ofadult rat offspring. Int J Neuropsychopharmacol
9: 201-208, 2006
20 Kobayashi S, Nomoto K, Watanabe M, Hikosaka
O, Schultz W, Sakagami M: Influences of re-warding and aversive outcomes on activity in
macaque lateral prefrontal cortex. Neuron 51:
861-870, 2006
21 Kono T, Matsuo K, Tsunashima K, Kasai K, Takizawa R, Rogers MA, Yamasue H, Fukuyama C,
Tanaka K, Yano T, Taketani Y, Kato N: Multiple-time repeatability of near-infrared spectroscopy recording during prefrontal activation task inhealthy men. Neurosci Res, in press
22 Kudo N, Kasai K, Itoh K, Koshida I, Yumoto M,
Kato M, Kamio S, Araki T, Nakagome K, Fukuda
M, Yamasue H, Yamada H, Abe O, Kato N, Iwanami A: Comparison between mismatch negativity amplitude and magnetic mismatch fieldstrength in normal adults. Biol Psychol 71: 54-62,
2006
23 Kunugi H, Hashimoto R, Okada T, Hori H, Nakabayashi T, Baba A, Kudo K, Omori M, Takahashi S, Tsukue R, Anami K, Hirabayashi N, Kosuga A, Tatsumi M, Kamijima K, Asada T, Harada
S, Arima K, Saitoh O: Possible association between nonsynonymous polymorphisms of theanaplastic lymphoma kinase (ALK) gene andschizophrenia in a Japanese population. J Neural
Transm 113: 1569–1573, 2006
24 Kuwabara H, Kasai K, Takizawa R, Kawakubo Y,
Yamasue H, Rogers MA, Ishijima M, Watanabe K,
Kato N: Decreased prefrontal activation during
letter fluency task in adults with pervasive developmental disorders: a near-infrared spectroscopy
study. Behav Brain Res 172: 272-277, 2006
25 Maeda K, Kasai K, Watanabe A, Henomatsu K,
Rogers MA, Kato N: The relationship between
subjective reasoning for medication adherence
and neurocognition in persons with schizophrenia.
Psychiatr Serv 57: 1203-1205, 2006
26 Marui T, Ikuko Funatogawa I, Koishi S, Yamamoto K, Matsumoto H, Hashimoto O, Nanba E,
Nishida H, Sugiyama T, Kasai K, Watanabe K,
Kano Y, Kato N, Sasaki T: Tachykinin 1 (TAC1)
gene SNPs and haplotypes with autism: a casecontrol study. Brain and Development, in press
27 Matsuo K, Glahn DC, Peluso MA, Hatch JP,
Monkul ES, Najt P, Sanche M, Zamarripa F, Li J,
Lancaster JL, Fox PT, Gao JH, Soares JC: Prefrontal hyperactivation during working memorytask in untreated individuals with major depres-86

sive disorder. Mol Psychiatry 12: 158-166, 2007
28 Matsumoto R, Haradahira T, Ito H, Fujimura Y,
Seki C, Ikoma Y, Maeda J, Arakawa R, Takano A,
Higuchi M, Suzuki K, Fukui K, Suhara T: Measurement of Glycine Binding Site of N-methylD-asparate (NMDA) Receptors in Living Human
Brain using 4-Acetoxy derivative of L-703,717,
4-Acetoxy-7-chloro-3-[3-(4-[11C] methoxybenzyl)
phenyl]-2(1H)-quinolone (AcL703) with PET.
Synapse, in press
29 Matsuo K, Kono T, Hatch JP, Seino K, Ohtani T,
Kato N, Kato T: A near-infrared spectroscopy
study of prefrontal cortex activation during a verbal fluency task and carbon dioxide inhalation in
individuals with bipolar disorder. Bipolar Disord,in press
30 Matsuoka K, Uno M, Kasai K, Koyama K, Kim Y:
Estimation of premorbid IQ in individuals with
Alzheimer’s disease using Japanese ideographic
script (Kanji) compound words: a Japanese version of NART. Psychiatry Clin Neurosci 60:
332-339, 2006
31 Minato T, Tochigi M, Kato N, Sasaki T: Association study between the cholecystokinin A(CCK-A) receptor gene and schizophrenia in theJapanese population. Psychiatr Genet, in press
32 Nishimura T, Imai H, Minabe Y, Sawa A, Kato N:
Beneficial effects of FK506 for experimental
temporal lobe epilepsy. Neurosci Res, in press
33 Nishiyama J, Tochigi M, Itoh S, Otowa T, Kato C,
Umekage T, Kohda K, Ebisawa T, Kato N, Sasaki
T: No association between the CNTF null mutation and schizophrenia or personality. Psychiatr
Genet 16: 217-219, 2006
34 Ohta M, Kano Y, Nagai Y: Catatonia in individuals with autism spectrum disorders in adolescenceand early adulthood: a long-term prospective
study. Int Rev Neurobiol 72: 41-54, 2006
35 Ohtani T, Kaiya H, Utsumi T, Inoue K, Kato N,
Sasaki T: Sensitivity to seasonal changes in panic
disorder patients. Psychiatr Clin Neurosci 60:
379-383, 2006
36 Okamura T, Kudo K, Sata N, Sameshima T, Doi N,
Kato N: Electroconvulsive therapy after coil embolization of cerebral aneurysm: a case report andliterature review. J ECT 22: 148-149, 2006
37 Otake T, Yoshinaga J, Seki Y, Matsumura T, Wa-

tanabe K, Ishijima M, Kato N: Retrospective inutero exposure assessment of PCBs with the preserved umbilical cords and its application tocase-control comparison. Environmental Healthand Preventive Medicine 11, 65-68, 2006
38 Otowa T, Tochigi M, Rogers M, Umekage T, Kato
N, Sasaki T: Insertional polymorphism of endogenous retrovirus HERV-K115 in schizophrenia.
Neurosci Lett 408: 226-229, 2006
39 Paraguison RC, Higaki K, Sakamoto Y, Hashimoto O, Miyake N, Matsumoto H, Yamamoto K,
Sasaki T, Kato N, Nanba E: Polyhistidine Tract
Expansions in HOXA1 Result in Intranuclear Aggregation and Increased Cell Death. Biochem Biophys Res Commun, in press
40 Rosario-Campos MC, Miguel EC, Quatrano S,
Chacon P, Ferrao Y, Findley D, Katsovich L, Scahill L, King RA, Woody SR, Tolin D, Hollander E,
Kano Y, Leckman JF: The Dimensional YaleBrown Obsessive-Compulsive Scale (DY-BOCS):
An instrument for assessing obsessive-compulsive
symptom dimensions. Mol Psychiatry 11: 495-504,
2006
41 Salisbury DF, Kuroki N, Kasai K, Shenton ME,
McCarley RW: Progressive and interrelated functional and structural evidence for post-onset brain
reduction in schizophrenia. Arch Gen Psychiatry,in press.
42 Shimabukuro M, Sasaki T, Imamura A, Tsujita T,
Fuke C, Umekage T, Tochigi M, Hiramatsu K,
Miyazaki T, Oda T, Sugimoto J, Jinno Y, Okazaki
Y: Global hypomethylation of peripheral leukocyte DNA in male patients with schizophrenia: apotential link between epigenetics and schizophrenia. J Psychiatr Res, in press
43 Takemura N, Kato N: Adult neurogenesis andsystemic adaptation: animal experiments andclinical perspectives for PTSD. Progress in Brain
Research, in press
44 Tochigi M, Otowa T, Hibino H, Kato C, Otani T,
Umekage T, Utsumi T, Kato N, Sasaki T: Combined analysis of association between personality
traits and three functional polymorphisms in thetyrosine hydroxylase, monoamine oxidase A, andcatechol-O-methyltransferase genes. Neurosci Res
54: 180-185, 2006
45 Tochigi M, Hibino H, Otowa T, Kato C, Marui T,

87

Ohtani T, Umekage T, Kato N, Sasaki T: Association between Dopamine D4 Receptor (DRD4)
Exon III polymorphism and Neuroticism in theJapanese Population. Neurosci Lett 398: 333-336,
2006
46 Tochigi M, Hibino H, Otowa T, Ohtani T, Ebisawa
T, Kato N, Sasaki T: No association of 5-HT2C,
5-HT6, and tryptophan hydroxylase-1 gene polymorphisms with personality traits in the Japanese
population. Neurosci Lett 403: 100-102, 2006
47 Tochigi M, Otowa T, Hibino H, Kato C, Marui T,
Ohtani T, Umekage T, Kato N, Sasaki T: No association between the Clara cell secretory protein(CC16) gene polymorphism and personality traits.
Prog Neuropsychopharmacol Biol Psychiatry 30:
1122-1124, 2006
48 Tochigi M, Kato C, Otowa T, Hibino H, Marui T,
Ohtani T, Umekage T, Kato N, Sasaki T: Association between the Corticotropin-Releasing Hormone Receptor 2 (CRHR2) Gene Polymorphism
and Personality Traits. Psychiatry Clin Neurosci
60: 524-526, 2006
49 Tochigi M, Zhang X, Ohashi J, Hibino H, Otowa
T, Rogers M, Kato T, Okazaki Y, Kato N, Tokunaga K, Sasaki T: Association study of the dysbindin (DTNBP1) gene in schizophrenia from theJapanese population. Neurosci Res 56: 154-158,
2006
50 Tochigi M, Otowa T, Suga M, Rogers M, Minato
T, Yamasue H, Kasai K, Kato N, Sasaki T: No
evidence for an association between the BDNF
Val66Met polymorphism and schizophrenia or
personality traits. Schizophr Res 87: 45-47, 2006
51 Tochigi M, Suga M, Ohashi J, Otowa T, Yamasue
H, Kasai K, Kato T, Okazaki Y, Kato N, Sasaki T:
No association between the metabotropic glutamate receptor type 3 gene (GRM3) and schizophrenia in a Japanese population. Schizophr Res
88: 260-264, 2006
52 Tochigi M, Zhang X, Ohashi J, Hibino H, Otowa
T, Rogers M, Kato T, Okazaki Y, Kato N, Tokunaga K, Sasaki T: Association study between the
TNXB locus and schizophrenia in a Japanese
population. Am J Med Genet Part B (Neuropsychiatric Genetics), in press
53 Utsumi T, Sasaki T, Shimada I, Mabuchi M, Motonaga T, Ohtani T, Tochigi M, Kato N, Nanko S:

Clinical features of soft bipolarity in major depressive inpatients. Psychiatr Clin Neurosci 60:
611-615, 2006
54 Washizuka S, Kametani M, Sasaki T, Tochigi M,
Umekage T, Kohda K, Kato T: Association of mitochondrial complex I subunit gene NDUFV2 at
18p11 with schizophrenia in the Japanese population. Am J Med Genet 141B: 301-304, 2006
55 Wati H, Kudo K, Qiao C, Kuroki T, Kanba S: A
decreased survival of proliferated cells in the
hippocampus is associated with a decline in spatial memory in aged rats: Neurosci Lett 399:
171-174, 2006
56 Yasuno F, Ota M, Ando K, Ando T, Maeda J,
Ichimiya T, Takano A, Doronbekov T.-K, Fujimura Y, Nozaki S, Suhara T: Role of ventral striatal dopamine D1 receptor in cigarette craving.
Biological Psychiatry: (Epub) 2006
57 Yoshikawa E, Matsuoka Y, Yamasue H, Inagaki M,
Nakano T, Akechi T, Kobayakawa M, Fujimori M,
Nakaya N, Akizuki N, Imoto S, Murakami K,
Kasai K, Uchitomi Y: Prefrontal cortex andamygdala volume in first minor or major depressive episode after cancer diagnosis. Biol Psychiatry 59: 707-712, 2006

88

Department of Neurology
Professor
Shoji Tsuji, M.D., Ph.D.

Associate Professor
Shin Kwak, M.D., Ph.D.

Lecturer
Yoshikazu Ugawa, M.D., Ph.D.
Jun Goto, M.D., Ph.D.

Associate
Jun Shimizu, M.D., Ph.D.,

Yasuo Terao, M.D.,Ph.D.,

Tomotaka Yamamoto, M.D.,Ph.D.,

Yaeko Ichikawa, M.D.,Ph.D.,

Yuji Takahashi, M.D.,PhD.

Homepage

http://square.umin.ac.jp/neurotky/

Introduction and Organization
The Department of Neurology was established by
the founder Professor Yasuo Toyokura in 1964 as one
Department in the Brain Research Institute. The Department of Neurology was succeeded by Professors
Toru Mannen and Ichiro Kanazawa. The organizationof the Brain Research Institute was reorganized as theDivision of Neuroscience of the Graduate School of
Medicine in 1997. We celebrated 40th Anniversary of
the Department of Neurology in 2004.

Clinical activities
We offer clinical services in the field of Neurology.
We are putting our effort to provide the patients withhighly advanced clinical practice as well as on clinicalactivities connected to postgraduate education of
Neurology.
We have outpatient clinics covering the broad fields
of Neurology. Furthermore, we also provide clinics
specialized to movement disorders, headaches, anddementia.
In the in patient ward, we offer programs for post-

graduate education including the program for the firststage postgraduate education. We also offer the excellent training program with the goal to get the board of
Neurologist. In 2005, we initiated deep brain stimulation for the treatment of movement disorders in cooperation with Department of Neurosurgery. Clinical
trials including that for polyglutamine disease and thatbased on vestibular nerve stimulation are being conducted.

Teaching activities
As for under-graduate education, our Department
takes a part in lectures of Neurology for the 4th and5th grade medical students, and bed-side learning forthe 5th grade medical students, and clinical clerkshipfor the 5th grade medical students.
In the bed-side learning we include small group
lectures covering neurological examination, neurophysiology, neuroradiology, neuropathology, neuropsychology, neuroimmunology, and neurogenetics. We
are also putting our effort for Free Quarters where weoffer various opportunities for medical students to be
involved in research activities, and 2-3 medical stu-

89

dents are conducting their research activities in thelaboratories.
In postgraduate education we offer the integrated
program including Neurology as the part of the program of Internal Medicine.
For training of board-certified Neurologists, we offer the excellent program including patients’care,training in Neurophysiology and Neuropathology,
consultation for Neurology, and supervising of juniortrainees. This program is integrated with clinical practice at the affiliated hospitals where rich experience isobtained for numerous cases in Clinical Neurology.
In Graduate School, we offer highly advanced research activities based on the interest of graduate students. In 2003, 21st Century COE program started in
the Neuroscience Division, and we are putting oureffort to establish excellent Institution for Neuroscience integrating basic and clinical neuroscience fields.

Research activities
Our research field covers broad fields related toneurological diseases, with the goals to elucidate themechanisms of neurological diseases, and to eventually develop new therapeutic strategies. Our research
activities include molecular genetics, developmental
biology, cell biology, pharmacology, pathology, andphysiology. We aim to integrate these broad research
fields to better contribute to clinical neurology.
In the filed of molecular genetics, we have develop
a high throughput DNA-microarray-based diagnostic
system. This system provides comprehensive analysesof genes including those for Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and familial spastic paraplegia. We have initiated multicenter-based consortium for multiple system atrophy. A
large-scale genome-wide analyses are being conducted to identify disease susceptibility genes. We
have established excellent animal models for dentatorubral-pallidoluysian atrophy, and conducting studies
for development of therapeutics. As the new protein
degradation pathway, the role of autophagy was investigated. (Tsuji, S., Goto, J., Shimizu, J., Takahashi,Y., Momose, Y., Date, H., Iwata, A., Fukuda, Y., Jin,Y., Suzuki, K., Nakahara, Y., Seki, N., Mitsui, J.,
Deoka, K.)
We have demonstrated that RNA editing of gluta-

mate receptor subunit GluR2 was significantly reduced in motor neurons in sporadic ALS patients in aneuronal class-selective and disease specific manner.
Since this molecular change is the primary causes ofneuronal death, research work on elucidation of theunderlying molecular mechanism and development ofspecific therapy for sporadic ALS is undergoing. We
have been investigating to what extent the vestibular
nerve stimulation is beneficial for alleviating parkinsonism and orthostatic hypotension in patients with
Parkinson disease and Shy-Drager syndrome. Validityof a wearable accelerometer in evaluating antiparkinsonism medication in outpatient clinic has been
also under investigation. (Kwak, S., Pan, W.D., Hideyama, T., Yamashita, T., Tanaka, T., Awabayashi,
K.)
The human neurophysiology section has been studying normal function of the human brain and pathophysiology for neurological disorders using several
non-invasive physiological methods, such as TMS,
EEG, MEG, fMRI, NIRS and ECG. Our final goal is todevelop a new therapeutic method for intractable disorders. One of them is deep brain stimulation (DBS)
which has been partly established. We began a physiological approach to elucidate the mechanisms for
DBS in the patients. We have also recently developed
a new, highly effective TMS method to induce longterm effects on the human brain using repetitive, monophasic magnetic stimuli. We have just stared a project to treat patients with movement disorders, intractable pain, epilepsy and so on using that new treatment. (Ugawa,, Y., Terao, Y., Hanajima, R., Okabe, S.,
Terada, S., Yugeta, A., Hamada, M., Matsumoto, H.,
Furubayashi, T., Mizuno, Y.)
In the field of neuromuscular diseases, we provide
diagnosis of neuromuscular pathology (muscle andnerve biopsies) and autoantibody testing for anti-ganglioside antibodies. Our neuromuscular pathology service evaluates approximately 100 neuromuscular biopsy specimens each year. In research field,
we focus on exploring the mechanism of inflammatory myopathies and immune mediated neuropathies.
We also focus on establishing improved methods ofdiagnosis and treatment of these diseases. Using clinical, pathological and molecular techniques, we aim toincrease understanding of the etiology and pathogenesis of neuromuscular diseases. (Shimizu, J., Hashi-

90moto, H., Tokimura, N., Tajiri, M., Mashiko, R.)

Publication
1. Kawahara Y, Sun H, Ito K, Hideyama T, Aoki M,
Sobue G, Tsuji S, Kwak S: Underediting of GluR2
mRNA, a neuronal death-causing molecularchange in sporadic ALS, does not occur in motor
neurons in SBMA patients or SOD1 transgenic
rats. Neurosci. Res. 54: 11-15, 2006
2. Struzik ZR, Hayano J, Soma R, Kwak S, Yamamoto Y: Aging of complex heart rate dynamics.
IEEE T Biomed. Eng. 53: 89-94, 2006
3. Sun H, Kawahara Y, Ito K, Kanazawa I, Kwak S:
Slow and selective death of spinal motor neurons
in vivo by intrathecal infusion of kainic acid: implications for AMPA receptor-mediated excitotoxicity in ALS. J. Neurochem. 98: 782-791,
2006.
4. Hideyama T, Momose T, Shimizu J, Tsuji S, Kwak
S: A PET study on the role of nigral lesions inparkinsonism in patients with ALS. Arch. Neurol.
63: 1719-1722, 2006.
5. Kwak S, Weiss JH: Calcium permeable AMPA
channel in neurodegenerative disease and ischemia. Curr. Opin. Neurobiol. 16: 281-287, 2006
6. Mitsui J, Saito Y, Momose T, Shimizu J, Arai N,
Shibahara J, Ugawa Y, Kanazawa I, Tsuji S, Murayama S. Pathology of the sympathetic nervous
system corresponding to the decreased cardiac
uptake in 123I-metaiodo- benzylguanidine(MIBG) scintigraphy in a patient with Parkinson
disease. J. Neurol. Sci. 243: 101-104, 2006
7. Saito Y, Matsumura K, Shimizu S, Ichikawa Y,
Ochiai K, Goto J, Tsuji S, Shimizu T. Pigmentary
macular dystrophy in spinocerebellar ataxia type 1.
J. Neurol. Neurosurg. Psychiat. 77: 1293, 2006
8. Sakai K, Yamada M, Sato T, Yamada M, Tsuji S,
Takahashi H. Neuronal atrophy and synaptic alteration in a mouse model of dentatorubralpallidoluysian atrophy. Brain 129: 2353-2362,
2006
9. Tada M, Shimohata T, Tada M, Oyake M, Igarashi
S, Onodera O, Naruse S, Tanaka K, Tsuji S, Nishizawa M. Long-term therapeutic efficacy andsafety of low-dose tacrolimus (FK506) for myasthenia gravis. J. Neurol. Sci. 247: 17-20, 2006

10. Terao Y, Mizuno T, Shindoh M, Sakurai Y, Ugawa
Y, Kobayashi S, Nagai C, Furubayashi T, Arai N,
Okabe S, Mochizuki H, Hanajima R, Tsuji S. Vocal amusia in a professional tango singer due to aright superior temporal cortex infarction. Neuropsychologia 44: 479-488, 2006
11. Yamada M, Shimohata M, Sato T, Tsuji S, Takahashi H. Polyglutamine disease: recent advancesin the neuropathology of dentatorubralpallidoluysian atrophy. Neuropathol. 26: 346-351,
2006
12. Shimizu J, Hashimoto M, Murayama S, Tsuji S
Neuropathology Education; A 52-year-old man
with hypohydrosis. Neuropathol. 26: 592-594,
2006
13. Soejima K, Sakurai H, Nozaki M, Fujiwara O,
Masuda M, Yamada H, Shimizu J. Surgical treatment of blepharoptosis caused by chronic progressive external ophthalmoplegia. Ann. Plast.
Surg. 56: 439-442, 2006.
14. Shinoe T, Wanaka A, Nikaido T, Kakuta Y, Masunaga A, Shimizu J, Duyckaerts C, Imaizumi K,
Iwamoto A, Kanazawa I. The pro-apoptotic human BH3-only peptide harakiri is expressed in
cryptococcus-infected perivascular macrophages
in HIV-1 encephalitis patients. Neurosci. Lett.
393: 102-107, 2006
15. Yuasa K, Arai N, Okabe S, Tarusawa Y, Nojima T,
Hanajima R, Terao Y, Ugawa Y. Effects of thirty
minutes mobile phone use on the human sensory
cortex. Clin. Neurophysiol. 117: 900-905, 2006
16. Mochizuki H, Ugawa Y, Terao Y, Sakai KL. Cortical hemoglobin-concentration changes under thecoil induced by single-pulse TMS in humans: asimultaneous recording with near-infrared spectroscopy. Exp. Brain. Res. 169: 302-310, 2006
17. Terao Y, Okano T, Furubayashi T, Ugawa Y: Effects of thirty-minute mobile phone use on visuo-motor reaction time task. Clin.. Neurophysiol.
117: 2504-2511, 2006
18. Matsumoto L, Yamamoto T, Higashihara M, Sugimoto I, Kowa H, Shibahara J, Nakamura K,
Shimizu J, Ugawa Y, Goto J, Dalmau J, Tsuji S.
Severe hypokinesis caused by paraneoplastic anti-Ma2 encephalitis associated with bilateral intratubular germ-cell neoplasm of the testes. Mov.
Disord. 22: 728-731, 2007

91

19. Shimohata, T, Hara, K, Sanpei, K, Nunomura, J,
Maeda, T, Kawachi, I, Kanazawa, M, Kasuga, K,
Miyashita, A, Kuwano, R, Hirota, K, Tsuji, S,
Onodera, O, Nishizawa, M. and Honma, Y. Novellocus for benign hereditary chorea with adult onset maps to chromosome 8q21.3- q23.3 Brain 130:2302-2309, 2007
20. Hara, K., Momose, Y., Tokiguchi, S., Shimohata,M., Terajima, K., Onodera, O., Kakita, A., Yamada, M., Takahashi, H., Hirasawa, M., Mizuno,
Y., Ogata, K., Goto, J., Kanazawa, K., Nishizawa,M., and Tsuji, S. Multiplex families with multiple
system atrophy. Arch. Neurol. 64: 545-551, 2007
21. Isoo, N, Sato, C, Miyashita, H, Shinohara, M, Takasugi, N, Morohashi, Y, Tsuji, S, Tomita, T, andIwatsubo, T. Aβ42 overproduction associated withstructural changes in the catalytic pore ofγ-secretase: common effects of Pen-2 aminoterminal elongation and fenofibrate. J. Biol. Chem.
282: 12388-12396, 2007
22. Terao Y, Ugawa Y, Yamamoto T, Sakurai Y, Masumoto T, Abe O, Masutani Y, Aoki S, Tsuji S.
Primary face motor area as the motor representation of articulation. J. Neurol. 254: 442-447, 2007
23. Takizawa Y, Kanda H, Sato K, Kawahata K, Yamaguchi A, Uozaki H, Shimizu J, Tsuji S, Misaki
Y, Yamamoto K. Polymyositis associated with focal mesangial proliferative glomerulonephritis
with depositions of immune complexes. Clin.
Rheumatol. 26: 792-796, 2007
24. Mochizuki H, Furubayashi T, Hanajima R, Terao
Y, Mizuno Y, Okabe S, Ugawa Y. Hemoglobin
concentration changes in the contralateral hemisphere during and after theta burst stimulation of
the human sensorimotor cortices. Exp. Brain Res.
180: 667-675, 2007
25. Hamada M, Hanajima R, Terao Y, Sato F, Okano T,
Yuasa K, Furubayashi T, Okabe S, Arai N, Ugawa
Y. Median nerve somatosensory evoked potentials
and their high-frequency oscillations in amyotrophic lateral sclerosis. Clin. Neurophysiol. 118:
877-886, 2007.
26. Hamada M, Hanajima R, Terao Y, Arai N, Furubayashi T, Inomata-Terada S, Yugeta A, Matsumoto H, Shirota Y, Ugawa Y. Origin of facilitation in repetitive, 1.5ms interval, paired pulse
transcranial magnetic stimulation (rPPS) of thehuman motor cortex. Clin. Neurophysiol. 118:

motor cortex. Clin. Neurophysiol. 118: 1596-1601,
2007
27. Hanajima R, Wang R, Nakatani-Enomoto S, Hamada M, Terao Y, Furubayashi T, Okabe S, Inomata-Terada S, Yugeta A, Rothwell JC, Ugawa Y.
Comparison of different methods for estimating
motor threshold with transcranial magnetic stimulation. Clin. Neurophysiol. 118: 2120-2122,
2007.
28. Terao Y, Furubayashi T, Okabe S, Mochizuki H,
Arai N, Kobayashi S, Ugawa Y: Modifying thecortical processing for motor preparation by repetitive transcranial magnetic stimulation. J.
Cogni. Neurosci. 19:1556-1573, 2007
29. Terao Y, Okano T, Furubayashi T, Akihiro Yugeta,
Satomi Inomata-Terada, Ugawa Y: Effects ofthirty-minute mobile phone use on saccades. Clin.
Neurophysiol. 118: 1545-1556, 2007
30. Mathew RM. Vandenberghe R. Garcia-Merino A.
Yamamoto T. Landolfi JC. Rosenfeld M R. Rossi
JE. Thiessen B. Dropcho EJ. Dalmau J.
Orchiectomy for suspected microscopic tumor inpatients with anti-Ma2-associated encephalitis.
Neurology 68: 900-905, 2007

92

Department of Neurosurgery
Professor
Nobuhito Saito, M.D.,Ph.D.

Associate Professor
Nobutaka Kawahara, M.D., Ph.D.

Lecturer
Tomoki Todo, M.D., Ph.D.,

Kensuke Kawai, M.D., Ph.D.,

Yasushi Ino, M.D., Ph.D.

Associate
Kyosuke Kamada, M.D., Ph.D.,

Jyunichi Tanaka , M.D.,

Minoru Tanaka, M.D., Ph.D.,

Akira Iijima, M.D.,

Keisuke Maruyama, M.D., Ph.D., Keisuke Takai, M.D,

Shigeo Sora, M.D.,
Ken Somekawa, M.D.,

Takahiro Ota, M.D.

Homepage

http://www.m.u-tokyo.ac.jp/neurosurg/

Introduction and Organization

Clinical activities

The Department of Neurosurgery at the Universityof Tokyo Hospital consists of 14 staff neurosurgeons,
who participate in the three major academic activities:
patient care, research and education. The staffs include a professor/chairman, two associate professors,
three lecturers and nine associates.
Clinical ward for Neurosurgery in our university
hospital was founded in 1951 as the first Neurosurgical clinic in Japan. Dr. Keiji Sano, as the founding
professor, established the Department of Neurosurgery
in 1962. Dr. Kintomo Takakura and Dr. Takaaki Kirino served as the second and the third professor. The
incumbent professor, Dr. Nobuhito Saito, has been
serving as the fourth professor since 2006.
Our department provides expertise for patients withbrain tumor, cerebro-vascular disease, spinal lesion,functional disorders, head trauma, etc.

General and specialized outpatient clinics are open
three days a week (Monday, Wednesday and Friday).
New patient are accepted two days a week (Tuesday
and Thursday). Specialized outpatient clinics are open
for patient with brain tumors, pituitary disease, spinal
disease, cerebrovascular disease, epilepsy, and gamma
knife treatment. From April 2006 through March 2007,
13,344 patients were treated at the outpatient clinics.
The Neurosurgery Ward has about 40 beds on theseventh floor of the new hospital building opened in
Sept. 2001. In 2005 and 2006, 600 and 674 patientswere admitted to the Neurosurgical Ward, respectively.
Three hundred and twenty two and 386 surgical procedures were performed with 140 and 98 gamma knife
precedures in each year. Our practice covers a wide
variety of neurosurgical diseases including malignant
and benign brain tumors, hemorrhagic and occlusive
cerebrovascular diseases, spinal disorders, epilepsy,
pain and movement disorders.
Intraoperative functional monitoring in brain tumor

93

surgery and pre- and intra-operative functional mapping in epilepsy surgery are frequently used to preserve brain function as much as possible. State-ofthe-art techniques including intraoperative computer-aided navigation and intravascular procedures
help our continuous effort to increase the safety ofsurgical treatment.
Our department is affiliated with 42 neurosurgicalinstitutions in and around the city of Tokyo including
15 university medical centers, where our residents andstudents are exposed to various pathologies. Surgicalcase volume in all hospitals exceeds 4000cases.

Teaching activities
Medical students take lectures of clinical neurosurgery in their second year. Clinical case studies andbedside teaching are scheduled in the third and fourthyears. The lecturers introduce general Neurosurgery as
well as the state-of-art Neurosurgical practice to thestudents. At the bedside teaching and clinical clerkship, they are offered opportunities to learn clinicalmanagement of Neurosurgical patients in the hands-on
style, and also are exposed to practice in various subspecialties in neurosurgery through special seminars
given by experts in the fields.
We accepted 5 residents in 2006 as a new residency
program. These residents are trained in the university
hospital and affiliated hospitals to experience every
aspects of neurosurgical practice for five years in average. Our residency training is finalized after thesixth year, when the finishing residents serve as seniorresident at the university hospital for 6 months. Academic training is provided through numerous intramural clinical and research conference, journal clubs
seminars as well as quarterly regional meeting of Japan Neurosurgical Society. After the residents finish
their training, or during training, they can choose to be
admitted into the Ph.D. course at the graduate schoolof Medicine, University of Tokyo, to be involved inadvanced basic research activities for 4 year. Aftercomplete training, our graduates stay in the department to be an associate in our or other university hospitals or become clinical staff in our affiliated hospitals.

Research activities
Clinical research in these two years have mainly
focused on treatment of acoustic neurinoma techniques of skull base surgery, treatment of malignant
brain tumors, radiosurgery and epilepsy surgery. The
results were presented at domestic and international
meetings including Annual Meetings of the Japan
Neurosurgical Society and Annual Meetings of American Association of Neurological Surgeons. .
Our department has been keeping prominent basic
research activities as well. The fields of our current
research are as follows
1) Pathogenesis of cerebral ischemia and neuronal
regeneration after ischemic brain damage
One of the major topics in recent basic science isto regenerate the brain with endogenous neuralprogenitors. Our laboratory has started basic research to regenerate neurons in vivo following
ischemic insult. We have demonstrated that the
40% of the lost neurons could be regenerated byadministration of growth factors. We also succeeded in regeneration of striatal neurons. Molecular mechanisms of adult neurogenesis are currently investigated using various models to enhance post-ischemic regeneration. By extending
the research into primate model, we are pursuingclinical application in the future.
2) Development of New Therapeutic Modalities for
Malignant Brain Tumors
Despite advances in microsurgical techniques, thepoor prognoses of malignant glioma patients havenot improved for decades. We develop a new
strategy by using replication-competent herpes
simplex viruses (HSV) that are genetically engineered to replicate in and kill tumor cells but notnormal cells. Using a third-generation oncolytic
HSV, we currently prepare a clinical trial on patients with progressive glioblastoma. Using our
HSV vector construction system, we further create
and test various oncolytic HSV vectors “armed”
with immunostimulatory genes.
We also practice optimized therapy based on the
results of genetic analyses routinely performed ontumor specimens obtained from glioma patients.
Currently, using polymeric micelles, we develop a
new mode of chemotherapeutic drug delivery sys-

94

tem for brain tumors.
3) Development and evaluation of functionpreserving and less invasive treatment of intractable epilepsy
We have been promoting the research on development, evaluation and standardization of thenovel treatment for intractable epilepsy. Since ourfacility is presently the only one that can provide
vagus nerve stimulation therapy in Japan, we aretrying to evaluate its efficacy and establish its significance in epilepsy treatment. Efficacy evaluation and development of surgical instruments has
been promoting for novel function-preserving
techniques, multiple subpial transection and multiple hippocampal transection. Basic and clinicalresearch on gamma knife treatment of epilepsy has
been performed as well.
4) Research on brain function using non-invasive andinvasive techniques
We have been studying human brain function using not only non-invasive techniques such as fMRI,
MEG, NIRS but also intracranial electrodes implanted in epilepsy patients. The latter is our markedly advantageous feature that enables us to obtain brain information with much higher spatial
resolution and SN ratio. We are planning to expand the research on this field to the study on
brain-computer interface in cooperation with otherbrain research laboratories and engineering laboratories.
5) Gamma knife radiosurgery
Our department is the first to introduce gamma
knife radiosurgery in Japan to treat various kindsof intracranial lesions including skull base tumors
or deep-seated brain arteriovenous malformations
with successful clinical result. We have particularly excellent achievement on treatment of brain
arteriovenous malformations; not only imaging
result but also effect on the risk of hemorrhage
was analyzed and reported in NEJM
352:146-53,2005. Moreover, the integration ofdiffusion-tensor tractography into gamma knife
treatment enabled us to confirm the dose to thecritical white matter fibers inside the brain, which
can be performed only in our department among
the world and can lead to safer treatment.
6) Clinical applications of the functional brain imag-

ing for neurosurgery
Our department intensively utilizes various kindsof functional imaging modalities including magnetoencephalography, functional MRI and diffusion tensor imaging-based tractography for presurgical brain mapping. Combining the results ofthe multi-modalities enables to visualize all cortical and subcortical networks of the motor, language and other cognitive functions in each patient.
Furthermore, we succeeded to import the combined information into a neuronavigation system(functional neuronavigation), which quickly andaccurately indicates the eloquent brain areas.

References
1. Arai K, Sato N, Aoki J, Yagi A, Taketomi-Takahashi
A, Morita H, Koyama Y, Oba H, Ishiuchi S, Saito N,
Endo K. MR signals of solid portion of pilocytic astrocytoma on MR T2-wighted imaging: Is it usefulfor differentiation from medulloblastoma? Neuroradiology 48:233-237, 2006
2. Furuya K, Kawahara N, Yamakawa Y, Kishida H,
Hachiya NS, Nishijima M, Kirino T, Kaneko K. Intracerebroventricular delivery of dominant negative
prion protein in a mouse model of iatrogenic
Creutzfeltdt-Jacob disease after dural graft transplantation. Neurosci Lett 402:222-226, 2006
3. Hara T, Kawahara N, Tsuboi K, Shibahara J, Ushiku
T, Kirino T. Sarcomatous transformation of clival
chordoma after charged-particle radiotherapy. J
Neurosurg 105:136-141, 2006
4. Honda F, Imai H, Ishikawa M, Kubota C, Shimizu T,
Fukunaga M, Saito N. Cilostazol attenuates bothgray and white matter damage in a rodent model of
focal cerebral ischemia. Stroke 37: 223-228, 2006
5. Imai H, Konno K, Nakamura M, Shimizu T, Kubota
C, Seki K, Honda F, Tomizawa S, Tanaka Y, Hata H,
Saito N. A new model of focal cerebral ischemia inthe miniature pig. J Neurosurg. 104 (2 Suppl):123132, 2006
6. Ino Y, Saeki Y, Fukuhara H, Todo T: Triple combination of oncolytic HSV-1 vectors “armed” with interleukin 12, interleukin 18 or soluble B7-1 results

95

in enhanced antitumor efficacy. Clin Cancer Res 12:

venous malformations of the brain. J Neurosurg643-652, 2006

(Suppl) 105:52-57, 2006

7. Itoh D, Aoki S, Maruyama K, Masutani Y, Mori H,

15. Miyamoto S, Hara T, Tabei Y, Honma H, Kondo T,

Masumoto T, Abe O, Hayashi N, Okubo T, Ohtomo

Oka S. Aneurysmal subarachnoid hemorrhage in a

K: Corticospinal tracts by diffusion tensor tracto-

patient with human immunodeficiency virus type 1graphy in patients with arteriovenous malformations.

infection. Case report. Neurol Med Chir (Tokyo)

J Comput Assist Tomogr 30:618-623, 2006

46:348-352,2006

8. Kamada K, Sawamura Y, Takeuchi F, Kuriki S, Todo

16. Okaji Y, Tsuno NH, Saito S, Yoneyama S, Tanaka M,

T., Morita A, Kirino T. Dissociated motor- and re-Nagawa H, Takahashi K. Vaccines targeting tumour

ceptive-language functions over bilateral hemi-

antigenesis- a novel strategy for cancer immuno-

spheres on MEG, functional MRI and Amobarbital

therapy, Eur J Surg Oncol 32:363-370, 2006

test:A case study and review of 4 reports. J Neurosurg 104; 598-607, 2006
9. Kawai K, Kamada K, Ohta T, Momose T, Aoki S,
Kawashima A, Saito N. Multiple hippocampal transection: seizure outcome and postoperative neuro-

17. Shimizu H, Kawai K, Sunaga S, Sugano H, Yamada
T. Hippocampal transection for treatment of left
temporal lobe epilepsy with preservation of verbal
memory. J Clin Neurosci 13: 322-328,2006
18. Shimizu T, Sugawara K, Tosaka M, Imai H, Hoya K,

psychometry. Epilepsia 47(Suppl 4): 12-13,2006

Takeuchi T, Sasaki T, Saito N. Nestin expression in

10. Kuroda T, Martuza RL, Todo T, Rabkin SD.

vascular malformations: a novel marker for prolif-

Flip-Flop HSV-BAC: bacterial artificial chromo-

erative endothelium. Neurol Med Chir (Tokyo).

some based system for rapid generation of recombi-

46:111-117, 2006

nant herpes simplex virus vectors using two inde-

19. Tanaka N, Sakurai K, Kamada K, Takeuchi F, et al.

pendent site-specific recombinases. BMC Biotech-

Neuromagnetic source localization of epileoptiform

nology 6: 40, 2006

activity in patients with graphogenic epilepsy. Epi-

11. Liu T, Zhang T, Fukuhara H, Kuroda T, Todo T, Ca-lepsia 47: 1963-1967, 2006

nron X, Bikfalvi A, Martuza RL, Kurtz A, Rabkin

20. Yonekura I,Takai K, Asai A, Kawahara N, Kirino T.

SD. Dominant-negative FGF receptor expression

p53 potentiates hippocampal neuronal death caused

enhances antitumoral potency of oncolytic HSV in

by global ischemia. J Cereb Blood Flow Metabneural tumors. Clin Cancer Res 12: 6791-6799,

26:1332-1340, 2006

2006
12. Liu T, Zhang T, Fukuhara H, Kuroda T, Todo T,
Martuza RL, Rabkin SD, Kurtz A. Oncolytic HSV
armed with platelet factor 4, an antiangiogenic agent,shows enhaced efficacy. Mol Ther 14: 789-797,
2006
13. Maruyama K, Shin M, Kirino T: Recent advances inradiosurgery for cerebral arteriovenous malformations: The University of Tokyo experience. in Kanno
T, Kato Y (eds.) Minimally Invasive Neurosurgery
and Multidisciplinary Neurotraumatology, SpringerVerlag Tokyo. 29-35, 2006
14. Maruyama K, Shin M, Tago M, Kurita H, Kawahara
N, Morita A, Saito N: Management and outcome ofhemorrhage after gamma knife surgery for arterio-

98

Department of
Molecular Preventive Medicine
Professor
Kouji Matsushima, M.D., Ph.D.

Associate Professor
Sho Ishikawa, M.D., Ph.D.

Research Associate
Shinichi Hashimoto, Ph.D.,

Nobuyuki Yamazaki,

Makoto Kurachi, M.D., Ph. D.,

Tetsu Nishiwaki, M.D., Ph. D.,

Takeshi Shimaoka, Ph.D.,

Satoshi Ueha, Ph. D.

Homepage

http://www.prevent.m.u-tokyo.ac.jp/

Introduction and Organization
The Department of Molecular Preventive Medicine
was originally established in 1885. It was designed tooffer both a high level of hygienic education and facilities for specialized research. At present, it is our
responsibility to give lectures, seminars and courses
for experiments and practical training on the preventive medicine to the third grade medical students. The
professor, several invited lecturers (including adjunctstaff) and six research associates take part in the education as well as research activities. There are overthirty members including research fellows, graduate
students and guest researchers in our department.

Teaching activities
The field of our department covers the wide area of
preventive medicine. The main scope of education
includes molecular mechanism of host defense responses to inciting environmental stimuli, free radicalchemistry and the environmental medicine with special reference to the relation between health and environment. The education is provided for the third grade
medical students. The course is consisted of lectures,
seminars, experiments and practical training are pro-vided by our own staffs and also by the experts outside: National Institute of Infectious Diseases (Dr.
Takebe), Kanazawa University (Dr. Matsugo), Kyoto
University (Dr. Koizumi), Environmental Science
Center of The University of Tokyo (Dr. Karima),
Health Service Center of The University of Tokyo (Dr.
Okubo), Toyama Medical and Pharmaceutical University (Dr. Inadera), Kyoto Prefectural University of
Medicine (Dr. Sakai), Shinshu University (Dr. Fukushima).

Research activities
We focus on several research fields as follows;
1) Establishment of pathophysiological roles ofchemokines and dendritic cells in vivo in various
animal disease models.
2) Molecular analysis of chemokine receptor signaling pathway.
3) Serial analysis of gene expression in various typesof cells and tissues in normal as well as diseasestate4) Development of vaccines against pathogenic microorganisms and cancer5) Establishment of a novel bio-monitoring systemfor environmental chemicals.

99

References
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Kanzawa N, Nishigaki K, Hayashi T, Ishii Y,
Furukawa S, Niiro A, Yasui F, Kohara M, Morita
K, Matsushima K, Le MQ, Masuda T, Kannagi
M. Augmentation of chemokine production by
severe acute respiratory syndrome coronavirus
3a/X1 and 7a/X4 proteins through NF-kappaB
activation. FEBS Lett. 2006;580(30):6807-12.
Zhu L, Ji F, Wang Y, Zhang Y, Liu Q, Zhang JZ,
Matsushima K, Cao Q, Zhang Y. Synovial
autoreactive T cells in rheumatoid arthritis resist
IDO-mediated inhibition. J Immunol. 2006;177(11):8226-33.
Suzukawa M, Komiya A, Iikura M, Nagase H,
Yoshimura-Uchiyama C, Yamada H, Kawasaki
H, Ohta K, Matsushima K, Hirai K, Yamamoto
K, Yamaguchi M. Trans-basement membrane
migration of human basophils: role of matrix
metalloproteinase-9. Int Immunol. 2006;18(11):1575-83.
Sakai N, Wada T, Yokoyama H, Lipp M, Ueha S,
Matsushima K, Kaneko S. Secondary lymphoidtissue chemokine (SLC/CCL21)/CCR7 signaling
regulates fibrocytes in renal fibrosis. Proc Natl
Acad Sci U S A. 2006;103(38):14098-103.
Tsunemi Y, Saeki H, Nakamura K, Nagakubo D,
Nakayama T, Yoshie O, Kagami S, Shimazu K,
Kadono T, Sugaya M, Komine M, Matsushima K,
Tamaki K. CCL17 transgenic mice show an enhanced Th2-type response to both allergic andnon-allergic stimuli. Eur J Immunol. 2006;36(8):2116-27.
Furuichi K, Wada T, Iwata Y, Kokubo S, Hara A,
Yamahana J, Sugaya T, Iwakura Y, Matsushima
K, Asano M, Yokoyama H, Kaneko S. Interleukin-1-dependent sequential chemokine expression and inflammatory cell infiltration inischemia-reperfusion injury. Crit Care Med.
2006;34(9):2447-55.
Wada T, Azuma H, Furuichi K, Sakai N, Kitagawa K, Iwata Y, Matsushima K, Takahara S,
Yokoyama H, Kaneko S. Reduction in chronic
allograft nephropathy by inhibition of p38 mitogen-activated protein kinase. Am J Nephrol.
2006;26(4):319-25.
Kurita S, Koyama J, Onizuka S, Motomura K,
Watanabe H, Watanabe K, Senba M, ApicellaMA, Murphy TF, Yoneyama H, Matsushima K,

9.

10.

11.

12.

13.

14.

15.

16.

Nagatake T, Oishi K. Dynamics of dendritic cell
migration and the subsequent induction of protective immunity in the lung after repeated airway challenges by nontypeable Haemophilus influenzae outer membrane protein. Vaccine. 2006;
24(31-32):5896-903.
Komiya A, Nagase H, Okugawa S, Ota Y, Suzukawa M, Kawakami A, Sekiya T, Matsushima K,
Ohta K, Hirai K, Yamamoto K, Yamaguchi M.
Expression and function of toll-like receptors inhuman basophils. Int Arch Allergy Immunol.
2006;140 Suppl 1:23-7.
Ezaki T, Kuwahara K, Morikawa S, Shimizu K,
Sakaguchi N, Matsushima K, Matsuno K. Production of two novel monoclonal antibodies that
distinguish mouse lymphatic and blood vascularendothelial cells. Anat Embryol (Berl). 2006;211(5):379-93.
Hara A, Wada T, Furuichi K, Sakai N, Kawachi
H, Shimizu F, Shibuya M, Matsushima K, Yokoyama H, Egashira K, Kaneko S. Blockade of
VEGF accelerates proteinuria, via decrease innephrin expression in rat crescentic glomerulonephritis. Kidney Int. 2006;69(11):1986-95.
Ishida Y, Kondo T, Kimura A, Matsushima K,
Mukaida N. Absence of IL-1 receptor antagonist
impaired wound healing along with aberrant
NF-kappaB activation and a reciprocal suppression of TGF-beta signal pathway. J Immunol.
2006;176(9):5598-606.
Kurashima K, Fujimura M, Myou S, Ishiura Y,
Onai N, Matsushima K. Asthma severity is associated with an increase in both blood CXCR3+
and CCR4+ T cells. Respirology. 2006;11(2):152-7.
Oka M, Norose K, Matsushima K, Nishigori C,
Herlyn M. Overexpression of IL-8 in the cornea
induces ulcer formation in the SCID mouse. Br J
Ophthalmol. 2006;90(5):612-5.
Sakai N, Wada T, Furuichi K, Shimizu K, Kokubo S, Hara A, Yamahana J, Okumura T, Matsushima K, Yokoyama H, Kaneko S. MCP-1/
CCR2-dependent loop for fibrogenesis in humanperipheral CD14-positive monocytes. J Leukoc
Biol. 2006;79(3):555-63.
Ohmori K, Fukui F, Kiso M, Imai T, Yoshie O,
Hasegawa H, Matsushima K, Kannagi R. Identification of cutaneous lymphocyte-associated antigen as sialyl 6-sulfo Lewis X, a selectin ligand
expressed on a subset of skin-homing helper

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17.

memory T cells. Blood. 2006;107(8):3197-204.
Zenclussen AC, Gerlof K, Zenclussen ML,
Ritschel S, Zambon Bertoja A, Fest S, Hontsu S,
Ueha S, Matsushima K, Leber J, Volk HD.
Regulatory T cells induce a privileged tolerant
microenvironment at the fetal-maternal interface.
Eur J Immunol. 2006;36(1):82-94.

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Department of Public HealthProfessor
Yasuki Kobayashi, M.D., Ph.D.

Associate Professor
Kazuo Inoue, M.D., Ph.D.

Lecturer
Hajime Sato, M.D., M.P.H., Ph.D., D.P.H.

Associate
Satoshi Toyokawa, Ph.D.

Homepage

http://publichealth.m.u-tokyo.ac.jp/

Introduction and Organization

Teaching activities

Public health departments in medical schools in Japan were introduced after the World War II, following
the model of the U.S. systems for public health andmedical education. The Department of Public Healthwas established in 1947, in the Faculty of Medicine, theUniversity of Tokyo. In 1995, the Department became apart of the Division of Social Medicine, Graduate
School of Medicine, as the result of the shift to a
graduate school system in the University of Tokyo.
The objectives of the Department are both education
and research of public health. The Department trains
graduate and undergraduate students through lectures,
seminars, field practice, and laboratory work in publichealth and occupational medicine, for the degrees ofMedical Doctor (MD), Master of Medical Sciences(MSc), and Doctor of Medical Sciences (equivalent to
Ph.D.).
The Department has conducted research on a wide
variety of public health issues, including health policy
and economics, occupational medicine, community andclinical epidemiology, and so on. In addition, the staff
members of the Department have offered public andoccupational health services to the governments, industries, and local communities.

1) Graduate Program
The Department offers special lectures, seminars,
field practice, and laboratory work on public health andoccupational medicine to graduate students. In thesetraining, special emphasis has been placed on the following points: (1) how to conduct epidemiologicalstudies, (2) how to use epidemiological and statisticalmethods, (3) how to use economic concepts and methods in the health fields, (4) how to establish the collaboration with health professionals in the various fields,and (5) how to read and write original papers.
Part of the seminars described above has been formally open to all students in the Graduate School of
Medicine as an intensive practice course on study
methods in public health. At the same time, the Department has provided the students enrolling in the
Master of Medical Science program with a short course
on public health.
2) Undergraduate Program
In the winter term of the fourth grade in the Schoolof Medicine (M2), students are provided with the following lectures: (1) current issues in the field of publichealth, (2) preventive services, (3) epidemiology, (4)health economics, (5) community health and primarycare (6) occupational and environmental health, (7) in-102

fection and tuberculosis control, (8) behavioral medicine, (9) international health, and (10) health policy inJapan. Similarly, in the sixth grade (M4), a concentration course of public health (e.g., health care systems,
occupational medicine, and community health practice)is provided. All the above lectures are given by faculty
members and part-time lectures including governmental
officials.
Field practice and laboratory work in public health isdue in the spring term of the fifth grade (M3), which is
jointly provided by Department of Molecular Preventive Medicine and the other departments related to public health fields. Averagely four to five students (small
group) are assigned to one special topic group with atutor (a faculty member or part-time lecturer). Eachgroup conducts field practice, review work, or laboratory work and writes a report in the style of original orreview paper. The reports submitted are bound andmade available to those students in subsequent years.
The Department also provides those lectures related
to public health and occupational medicine for undergraduate students in the School of Health Sciences andNursing, and the Faculty of Engineering.

Research activities
1) Health policy and economics
We are interested in the topics of health care systemand economics in general. We have performed and published those studies related to supply and demand sidesof health services in Japan; such as supply and distribution of physicians, the separation of pharmaceuticaldispensing and prescribing in medical practice, coststudies of outpatient and inpatient services, and the efficiency and equity issues of the Japan's health insurance system. We have also carried on several policy
studies in terms of public awareness of medical technology. These studies have been published in some international policy journals. We have continued a collaborative study on a system of HIV/AIDS care with
the introduction of highly active anti-retroviral therapy(HAART) in developing countries, since such a system
involves medical, behavioral, social, and economic
factors, and would inevitably become an important
health policy issue.
2) Occupational health
We have carried on a longitudinal study on life-styleand health status of workers in various occupationalsettings for the purpose of preventing occupational andlife-style diseases. We have also tackled the issues ofhealth effects of lead and other heavy metals and solvents, and health effects of pesticides in developing
countries.
3) Community and clinical epidemiology
We have done several epidemiological studies incommunity, such as activities of daily living (ADL) forthe community elderly, as well as those studies in clinical epidemiology. Most of these studies have been carried on in collaboration with local communities orclinical departments.

References
1. Vigeh M, Yokoyama K, Ramezanzadeh F, Dahaghin M, Sakai T, Morita Y, Kitamura F, Sato H,
Kobayashi Y. Lead and other trace metals in preeclampsia: A case-control study in Teheran, Iran.
Environmental Reseach 2006; 100: 268-275.
2. Inoue K, Shono T, Toyokawa S, Kawakami M.
Body mass index as a predictor of mortality incommunity-dwelling seniors. Aging Clinical andExperimental Research 2006; 18: 205-210.
3. Inoue K, Shono T, Matsumoto M. Absence of outdoor activity and mortality risk in older adults living at home. Journal of Aging and Physical Activity
2006; 14: 203-211.
4. Inoue K. Venous thromboembolism in earthquake
victims. Disaster Management and Response 2006;
4: 25-27.
5. Matsumoto M, Inoue K, Kaiji E. Fasting plasma
glucose and its relationship to future diabetes mellitus and white blood cell count: a longitudinal
study in a rural Japanese population. Jichi Medical
University Journal 2006; 29: 115-123.
6. Sato H, Akabayashi A, Kai I. Appraisal of thepolicymaking process in Japan for gene therapy:
Results of the national surveys of academic societies, hospitals, and medical schools. Medical Science Monitor 2006; 12: 7-15.
7. Sato H, Akabayashi A, Kai I. The development ofpublic opinion on advanced medical technologies
and experts’ views on their acceptance of thesetechnologies - the case of organ transplant and gene

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therapy in Japan. Health Care Analysis 2006; 14:203-214.
8. Shinozaki M, Watanabe T, Sato H, Nagawa H.
Chronic colitis promotes tumor development. Oncology Reports 2006; 15: 1485-1490.
9. Toyokawa S, Kitajima T, Kobayashi Y, Sato H,
Chaipah W, Thuennadee R. Health insurance status
and access to antiretroviral treatment among HIV/
AID patients in Northeast Thailand - A patientbased analysis. Journal of International Health2006; 21: 129-135.
10. Nakata A, Ikeda T, Takahashi M, Haratani T, Hojou
M, Fujioka Y, Araki S. Non-fatal occupational injury among active and passive smokers in smalland medium-scale manufacturing enterprises in Japan. Social Science & Medicine 2006; 63: 24522463.
11. Nakata A, Ikeda T, Takahashi M, Haratani T, Hojou
M, Fujioka Y, Swanson NG, Araki S. Impact of
psychosocial job stress on non-fatal occupational
injuries in small and medium-sized manufacturing
enterprises. American Journal of Industrial Medicine 2006; 49: 658-669.
12. Nakata A, Ikeda T, Takahashi M, Haratani T, Hojou
M, Swanson NG, Fujioka Y, Araki S. The prevalence and correlates of occupational injuries insmall-scale manufacturing enterprises. Journal of
Occupational Health 2006; 48: 366-376.
13. Sabawoon W, Sato H, Inoue K, Kobayashi Y.
Health condition in Afghanistan and the basic
health package of health services. Journal of Conference for Emergency Medicine in Rural Areas
and Isolated Islands 2006; 7: 57-63.

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Department of Forensic Medicine
Professor
Ken-ichi Yoshida, M.D., Ph.D.

Lecturer
Kouichi Uemura, M.D., Ph.D.

Associate
Kou Takahashi, M.D, Ph.D.,

Homepage

Kaori Shintani, Ph.D.

http://plaza.umin.ac.jp/~forensic/

Introduction and Organization
Associate Professor Kuniyoshi Katayama lectured“judicial medicine” in University of Tokyo since1882 before our department was founded as the firstdepartment of forensic medicine in Japan in 1888. He
renamed “judicial medicine” to “forensic medicine”
in 1891 since the department should cover legislation
as well as general forensic practices. Dr. Katayama
became the first professor of forensic medicine in Japan.
The 2nd Professor Sadanori Mita also founded theserological department (Department of Immunology atpresent). He discovered the antigen-antibody reaction
and complement fixation reaction.
The 3rd Professor Tanemoto Furuhata was the famous for ABO blood group genetics, and also contributed the development of criminology. He autopsied
several cases of historical crimes.
The 4th Professor Shokichi Ueno discovered thecomplex III. He helped foundation of national police
academy for death investigators.
The 5th Professor Toshiyuki Miki could not perform
autopsy for four years due to the University of Tokyo
strike. However, he left many achievements in thefield of blood typing and paternity examination.
The 6th Professor Ikuo Ishiyama encouraged forensic pathology. He also introduced DNA fingerprinting
and PCR technique in the forensic practices.
The 7th Professor Takehiko Takatori studied thebiochemical changes of the lipid in cadavers. He dis-sected five victims of sarin subway attacks in Tokyoand identified sarin in tissue by a sophisticatedmethod.
The present Professor Ken-ichi Yoshida has studied
on the mechanism of ischemic heart disease and sudden cardiac death related to psychological stress, withrespect to gap junction, intracellular signaling, andproteolysis. Additionally, the death investigation system on unnatural death and medical practice-related
death is another topic of study.
The department currently has one professor, one
lecturer, one assistant professor, one associate, two
special technicians, eight postgraduate students, andtwo researchers.

Forensic autopsy
The determination of precise cause of death is themost important work in our department. We autopsy
80-90 criminal cases in eastern part of Tokyo every
year. We have already autopsied more than 10000
cases since 1889. Some of these cases are very famousin criminology in Japan.
In forensic autopsy, we examine the pathological,
alcohol, toxicological, and blood type testing of eachcase, too. Finally, forensic pathologists in our department diagnose the cause of death. Official documents
written in our forensic judgments are so precious that
we keep them since first autopsy case in 1889. We
have serious responsibility in the determination of
cause of death.

107

Since 2005, we also performed autopsies on medical practice-related deaths (MPAD) in corroboration
with Department of Human Pathology. Both departments lead the pilot study on the investigation andanalysis of MPAD (supported by government). We
also contribute to evolve new way of presenting expert opinions for the jury courts that will be enacted in2009.

Teaching activities
As for under-graduate education, our department
provides lectures for the 4th year medical students,
Free Quarter training course for the 3-4th year medical
students, and Clinical Clerkship learning for the 5thyear medical students.
The lectures are based on the autopsy and court
cases for the better understanding of the death investigation and medical law. In the Free Quarter training
course, students experience laboratory practices(toxicology, DNA typing, histology) or experiments.
In the clinical clerkship, each student experiences theprocess from autopsy to presentation of expert opinion.
They can also attend the practices of medical examinerʼs activities and the court.
In addition, students of school of public health andlaw school are provided with somewhat practical lectures with exercises.

Research activities
Our research is wide ranged from social issues tomolecular biology. Main research interest in our department is as follows:More than two thirds of the causes of unusual death
are ischemic heart disease. Psychological stress from
accidents, assaults, and restraint often triggers these
deaths. To diagnose ischemic heart attack and sudden
death due to psychological events, we study on themechanism of myocardial death due to ischemia-reperfusion, with respect to intracellular signaling
system and calcium-dependent protease (calpain). We
have focused recently on the implication of thechanges in gap junction (GJ) component conexin 43 to
the arrhythmogenesis and sudden death in the settingsof acute myocardial infarction and psychologicalstress (by restraint). The implication of GJ in the de-velopment of contraction band necrosis (histologicalsign of early stage of heart attack) and myocardial
infarction through Ca2+-dependent protease calpain is
another target. On the other hand, the death investigation system and information disclosure on “unusual
death” and medical practice-related death have been
also studied.

References
1. Uemura K, Kikuchi Y, Shintani-Ishida K, Nakajima M, Yoshida K. A fatal case of post-operative
pulmonary thromboembolism with cosmetic liposuction. J Clin Forensic Med. 2006;13(1):41-3.
2. Shintani-Ishida K, Nakajima M, Uemura K, Yoshida K. Ischemic preconditioning protects cardiomyocytes against ischemic injury by inducing
GRP78. Biochem Biophys Res Commun. 2006;
345(4):1600-5.
3. Ikegaya H, Nakajima M, Shintani-Ishida K, Uemura K, Yoshida K. Death due to duodenal obstruction in a patient with an eating disorder: acase report. Int J Eat Disord. 2006;39:350-2.
4. Ikegaya H, Saka K, Sakurada K, Nakamura M,
Yoshida K. A case of sudden death after intramuscular injection of butylscopolamine bromide.
Legal Med. 2006;8(3):194-7.
5. Ikegaya H, Kawai K, Kikuchi Y, Yoshida K. Does
informed consent exempt Japanese doctors from
reporting therapeutic deaths? J Med Ethics.
2006;32(2):114-6.
6. Kimura H, Shintani-Ishida K, Nakajima M, Liu S,
Matsumoto K, Yoshida K. Ischemic preconditioning or p38 MAP kinase inhibition attenuates
myocardial TNF alpha production and mitochondria damage in brief myocardial ischemia. Life
Sci. 2006;78(17):1901-10.
7. Kimura H, Mukaida M, Kuwabara K, Ito T,
Hashino K, Uchida K, Matsumoto K, Yoshida K.
4-Hydroxynonenal modifies IgA in rat intestine
after lipopolysaccharide injection. Free Radic Biol
Med. 2006;41(6):973-8.
8. Inoue H, Ikeda N, Ito T, Tsuji A, Kudo K. Homicidal sharp force injuries inflicted by family
members or relatives. Medicine, Sciences andLaw. 2006;46(2):135-40.

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Department of Medical
Informatics and Economics
Professor
Kazuhiko Ohe, M.D.,Ph.D.

Homepage

http://www.m.u-tokyo.ac.jp/medinfo/

Introduction and Organization
The Department of Medical Informatics and Economics aims to reform medical systems and make social contribution by applying information technology to
medical field such as medical economics and hospitalmanagement. The department develops basic methods
that are applicable to medical information systems inthe boundary area of healthcare and information science,
establishes infrastructures for information environment
where medical information are utilized effectively, andapplies knowledge and technique acquired throughthese efforts to medical and healthcare field.
The main keywords of the target domain are medical
and clinical information systems, next-generation electronic health record systems, virtual health care environment, computer representations and standardizationof medical concepts, ontology, medical knowledge engineering, hospital epidemiology, quality assessment ofhealthcare, clinical and bioinformatics engineering,privacy protection and encryption, analysis of hospitalmanagement, safety management in healthcare.
The professor of the department also holds the position of director of the department planning, informationand management (DPIM) in the University of Tokyo
Hospital. DPIM is the department that deals with information analyses and future planning for the University of Tokyo Hospital by using information systems aswell as the planning, design, development, and operation of information systems for the whole hospital. The
DPIM was newly established on April 1, 2003, after
integration of the Hospital Computer Center and the
project team for hospital development, which separately

existed until the end of March, 2003.
Since the professor runs the Department of Medical
Informatics and Economics with staffs of DPIM, they
are practically the same organization. Therefore, educations and researches in the graduate course are promoted together with DPIM activities. Only one professor is the official faculty member of the Department ofMedical Informatics and Economics, however, facultyoutside the department participates as teaching staffs ofthe graduate course: Assoc. prof. T. Imamura and Lecturer. K. Miyo from DPIM, Prof. T. Kiuchi from UMIN
center, Visiting assoc. prof. S. Oku from the Department of Healthcare Related Informatics that is the affiliated department (April 2004 - ), Visiting assoc. Prof.
H. Hashimoto from the Department of Health Management and Policy that is also the affiliated department(Oct. 2005 - ), Assoc. Prof. R.Yamamoto from Interfaculty Initiative in Information Studies, Graduate Schoolof Interdisciplinary Information Studies, and Prof. H.
Oyama and Assoc. Prof. Y. Onogi from Division ofClinical and Bioinformatics Engineering, Departmentof Clinical Bioinformatics, Graduate School of Medicine.
The origin of the Department of Medical Informatics
and Economics dates back to 1983 when the hospitalcomputer center was officially approved as one of thecentral clinical service facilities in the hospital. At thesame time, the doctor’s course for medical informatics
was established. The first professor was Dr. Shigekoto
Kaihara, who is the founder of medical informatics inJapan, and he is now a emeritus professor of the University of Tokyo. In accordance with the reform to theuniversity with graduate school curriculum in the uni-

109

versity of Tokyo, the Department of Medical Informatics and economics was established in present divisionof social medicine in 1997. Then, one professor and one
associate professor belonging to the hospital computer
center moved to the department. In 2000, medical informatics field was set up in the Interfaculty Initiativein Information Studies, Graduate School of Interdisciplinary Information Studies. One post for associate
professor was transferred from the Department ofMedical Informatics and economics to the Interfaculty
Initiative in Information Studies and then our department started the wide acceptance of students. Assoc.
prof. Y. Onogi assumed the start-up position, and now
Assoc. prof. R. Yamamoto takes over the post.
The department is located on the fourth floor in Administration and Research Building in the University ofTokyo Hospital.

Teaching activities
The department offers the Medical Science Doctoral
course (4-year program). The eligibility for admission
is open to those who graduate from a 6-year undergraduate program at the School of Medicine and those
who have master’s degrees either in the University ofTokyo or any other institutions. It does not need to havea medical license to apply for admission. Students will
receive Doctor’s degree in Medical Science with completion of required units and passing a doctoral thesis.
The department is collaborating with the health informatics course in the division of Health Sciences andNursing at the Graduate School of Medicine. Although
the department formally belongs to the Division of Social Medicine, it offers the course of health informatics
for students in the division of Health Sciences andNursing. Therefore most faculty members in this department also supervise the students in the Health Informatics course. The Health Informatics course offers
2-year master’s course program and 3-year doctoral
course program. Completing required units and passing
thesis, the master’s course students will receive Master’s degree in Health Science and the doctoral course
student will receive Doctor’s degree in Health Science.
Furthermore our department accepts the students inthe master’s course of Medical Science.
In this master’s course, all students spend the first
four months on the planned coursework, then will de-cide which department they wish to be enrolled. Afterassignment of each department, students conduct theirresearches and complete master’s thesis over remaining
one and half year. Completing the required units andpassing the thesis, they will receive the Master’s degree
in Medical Science.
The enrolled students in FY2006 are seven in doctor’s course for Medical Informatics and Economics,
two in doctor’s course for Health Informatics, and two
in master’s course for Health Informatics.
The students’ researches cover various topics. The
main ones are the analysis of medical cost for the DPC
Classification”, development of method for medical
ontology, a study on the communication model between
healthcare professionals and patients, a study on methods for healthcare safety control, medical support byelectronic description format of chemical therapy regimen and inference mechanism, and so on.

Research activities
In 2006 F.Y., research staffs are Prof. Kazuhiko Ohe,
Assistant Professor Kengo Miyo, Project Associate Hiroki Watanabe, Research Associate Izumi Yamaguchi,
hiroo Ide, Hideo Yasunaga, Katsuya Tanaka, and Project Research Associate Eiji Aramaki, Takeshi Imai,
Megumi Sato, Nozomi Nakahashi, Yuki Nittami(Sumita), Hiroyuki Hoshimoto, Shiro Matsuya, andAkihisa Watanabe.
Our main research domains are 1) application studies
on developments of clinical information systems as
typified by hospital information system and electronic
health records system, 2) studies on medical safetycontrol systems, 3)medical knowledge discovery andanalysis of medical economics indicators by using databases of hospital information system and electronic
health records system, 4) structured representations andstandardization of medical terms and concepts, 5) privacy protection and security in healthcare information
systems, 6) information analysis on food safety, 7)
analysis of various issues on DPC, 8) application ofvirtual environment for healthcare.
In these domains, major research topics are as listed
below.
3) A study on development methods for large scale
ontology databases of medical terms and concepts :110This research develops the methods to build thelarge scale medical ontology, which is a databasefor hundreds of thousand of clinical terms and concepts and their relationships. It focuses on the development of basic methods for making and accessing databases and will be applied for the research described in 6).
4) A study on a bedside system for automatic security
surveillance
Existing bedside system for security control is justchecking the barcodes or IC tags of medical products, patients and staffs. This control depends on
conscious and active acts of staffs. This research,however, develops a method to achieve automatic
detection of approaching objects by applying various information engineering methods. It is expected that the mix ups of objects are prevented
before they occur.
5) A study on the development of a patient-oriented,
event-driven, and intellectual clinical support subsystem (Industry-academia collaboration projectwith Fujitsu Limited, 2004-2008)
This research develops autonomic, distributed,
real–time clinical support system. This system will
be tested by being incorporated in the information
system of the university of Tokyo Hospital.
6) Construction of Clinical and Medical Ontology
Database (Industry-academia collaboration projectwith the Japan Anatomy Laboratory, Co, Ltd.,
2004-2008)
This research aims the construction of actuallyavailable clinical and medical ontology with approximately 200,000 terms. It also develops application tools for the ontology.

References
1. Eiji Aramaki, Takeshi Imai, Kengo Miyo, Kazuhiko
Ohe: Automatic Deidentification by using Sentence
Features and Label Consistency, Workshop on
Challenges in Natural Language Processing for
Clinical Data, 2006
2. Eiji Aramaki, Takeshi Imai, Kengo Miyo, Kazuhiko
Ohe: Patient Status Classification by using Rulebased Sentence Extraction and BM25-kNN based
Classifier, Workshop on Challenges in Natural Language Processing for Clinical Data, 2006

3. Ide H. The impact of the DPC payment system on
hospital productivity change in Japan. AcademyHealth Annual Research Meeting. Seattle, WA,
USA. 2006
4. Shinohara N, Oyama H, Matsuya S, Ohe K. Computational Method of Identifying Medical Complications Based on Hospital Information System Data.
Proceedings of AMIA annual symposium 2006.
2006:1093.
6. Yuki Sumita, Mami Takataa, Keiju Ishitsukab, Yasuyuki Tominaga and Kazuhiko OHE: Building areference functional model for EHR systems International Journal of Medical Informatics, Epub
URL: http://dxdoiorg/101016/jijmedinf20066008 ,2006
7. Hideo YASUNAGA, Hiroo IDE, Tomoaki
IMAMURA, and Kazuhiko OHE: Willingness topay for health care services in common cold, retinal
detachment, and myocardiac infarction: an internet
survey in Japan BMC Health Service Reserch,
2006：12, Epub URL:
http://wwwbiomedcentralcom/1472-6963/6/12
8. Hideo YASUNAGA, Hiroo IDE, Tomoaki
IMAMURA, and Kazuhiko OHE: Analysis of Factors Affecting Willingness to Pay for Cardiovascular Disease-Related Medical Services International
Heart Journal, 47(2), 273-286, 2006
9. Hideo YASUNAGA, Hiroo IDE, Tomoaki
IMAMURA, and Kazuhiko OHE: Influence of Japan's New Diagnosis Procedure Combination-Based Payment System on the Surgical Sector:
Does it Really Shorten the Hospital Stay? Surgery
Today, 36(7), 577-585, 2006
10. Yasunaga H, Ide H, Imamura T, Ohe K: The Measurement of Willingness to Pay for Mass Cancer
Screening with Whole-Body PET (Positron Emission Tomography) Annals of Nuclear Medicine,20(7), 457-462, 2006
11. Yasunaga H, Ide H, Imamura T, Ohe K: Benefit
evaluation of mass screening for prostate cancer:
willingness-to-pay measurement using contingent
valuation Urology 68(5), 1046-1050, 2006

112

Department of Cardiovascular
Medicine
Professor
Ryozo Nagai, M.D., Ph.D.

Associate Professor
Yasunobu Hirata, M.D., Ph.D.

Lecturer
Yoshinori Seko, M.D., Ph.D.,

Hiroshi Yamashita, M.D., Ph.D.

Hospital Lecturer
Nobukazu Ishizaka, M.D., Ph.D.,

Homepage

Koji Maemura, M.D., Ph.D.

http://plaza.umin.ac.jp/~utok-card/

Introduction and Organization
The Department of Cardiovascular Medicine is actively involved in clinical medicine, basic researchand teaching. In line with the rapidly evolving andprogressing nature of modern treatment of cardiovascular diseases, our department has changed dynamically during the recent years. Not only do we have themost highly advanced equipment and facilities (e.g.
24-hour cardiac care unit), but are personnel are also
highly trained to be well knowledged and expert in themost modern methods of diagnosis and treatment. Asa teaching and research hospital, we also emphasize
the development and incorporation of new treatments
if they may benefit the patient. From a research standpoint, our interests range throughout all fields of cardiovascular medicine ranging from molecular biology
to clinical research including genomics. Importantly,
our research interests are aimed at making possible
new diagnostics and treatment of cardiovascular diseases. Finally, we have a particular interest in teaching
not only for medical students but also for residents
which is important for the future of cardiovascular
medicine.
Outline of department

Staff: one professor (Ryozo Nagai), 1 associate professor (Yasunobu Hirata), 2 assistant professors (outpatient clinic Yoshinori Seko and hospital ward Hiroshi Yamashita), 15 research associates, 9 staff members, 30 graduate school students, 6 researchers, 1
members on leave and 2 members studying abroad.

Clinical activities
In 2006, 1,322 patients were newly admitted to our
hospital ward of approximately 50 beds. Of these patients, approximately 70% were due to ischemic heartdisease. Cardiovascular angiograms were conducted in
1,722 patients, of which 581 cases were interventional
procedures. For arrhythmias, there were 54 cases of
implantation of a pacemaker, 45 cases of catheter ablation, and other specialized pacemaker devices suchas 11 cases of implantation of a cardioverterdefibrillator, and 5 cases of implantation of a cardiac
resynchronization device.
As we are an authorized facility for heart transplantation, left ventricular assist device (LVAD) use
for severe heart failure cases has been increasing. This
year, the first case of heart failure from our department underwent a heart transplant procedure at the
Department of Cardiovascular Surgery. Duration of

113

hospitalization is on average 13.0 days.
Out-patient clinics are available as part of the Department of Medicine or as a specialized department.
Patient numbers are increasing each year to 43,612 in
2006. The profile of diseases includes ischemic heartdisease in main in addition to hypertension and peripheral artery disease. Out-patient clinics are open
both mornings and afternoons from Monday to Friday.
Approximately 190 patients visit each day. Acutecases of coronary heart disease and aortic disease arealso a focus of the department, as emergent catheterization is available on a 24-hours basis.

Teaching activities
As a division of the Department of Medicine, medical diagnostics training, general cardiovascular medicine, clinical lectures and bedside teaching are courses
available at the medical school. For bedside teaching,
two students are placed under the guidance of one
research associate allowing for teaching in small
groups. Specialized groups provide lectures. As forpost-graduate education, residents are educatedthrough specialized group conferences, chart rounds,
grand rounds and clinical conferences.

Research activities
Areas of interest are as follows:
1. Regulated expression of smooth muscle myosin
heavy chain
2. Mouse genetic models of cardiovascular diseases
and vascular development
3. Differentiation of smooth muscle cells
4. Genetic risk analysis of atherosclerosis
5. Mechanism of post-PTCA restenosis
6. MRI in cardiovascular diseases
7. Gene expression and regulation in cardiomyocytes
8. Nitric oxide and endothelial function
9. Aerobic threshold and cardiac rehabilitation
10. Molecular analysis of myosin light chain mutations in familial hypertrophic cardiomyopathy
11. Clock gene in cardiovascular diseases
12. Early diagnosis of ischemic heart disease using
visualization techniques of coronary arteries
13. Immunological basis of myocarditis and dilated
cardiomyopathy

14. Anti-arrhythmia therapy using catheter ablation
15. New treatment for pulmonary hypertension
16. Development of drug eluting stent
17. Clinical application of vasoactive substances for
cardiorenal insufficiency
18. Bone marrow-derived cells in atherosclerosis
19. Regeneration therapy for cardiovascular disease

References
1. Abe M, Sata M, Suzuki E, Takeda R, Takahashi M,
Nishimatsu H, Nagata D, Kangawa K, Matsuo H,
Nagai R, Hirata Y. Effects of adrenomedullin on
acute ischemia-induced collateral development
and mobilization of bone marrow-derived cells.
Clin Sci (Lond). 2006; 111: 381-7.
2. Doi H, Iso T, Sato H, Yamazaki M, Matsui H, Tanaka T, Manabe I, Arai M, Nagai R, Kurabayashi
M. Jagged1-selective Notch signaling inducessmooth muscle differentiation via a RBP-J{kappa}-dependent pathway. J Biol Chem. 2006;
281: 28555-64.
3. Hara K, Horikoshi M, Yamauchi T, Yago H, Miyazaki O, Ebinuma H, Imai Y, Nagai R, Kadowaki
T. Measurement of the high-molecular weight
form of adiponectin in plasma is useful for theprediction of insulin resistance and metabolic
syndrome. Diabetes Care. 2006; 29: 1357-62.
4. Hasegawa H, Takano H, Kohro T, Ueda K, Niitsuma Y, Aburatani H, Komuro I. Amelioration of
hypertensive heart failure by amlodipine may occur via antioxidative effects. Hypertens Res 2006;
29: 719-29.
5. Iida H, Kurano M, Takano H, Oonuma H , Imuta
H , Kubota N , Morita T , Meguro K , Sato Y ,Abe T , Yamazaki Y , Nakajima T : Can KAATSU
be used for an orthostatic stress in astronauts?: Acase study. Int J KAATSU Training Res. 2006; 2:45-52.
6. Ishizaka N, Nagai R. Evaluation and managementof chronic heart failure. JMAJ (Japan Medical
Association Journal). 2006; 49: 180-3.
7. Ishizaka N, Ishizaka Y, Toda E, Nagai R, Yamakado M. Association between smoking, hematological parameters, and metabolic syndrome inJapanese men. Diabetes Care 2006; 29: 741.
8. Ishizaka N, Hashimoto H, Ishizaka Y, Toda E,

114

Nagai R, Yamakado M. Metabolic syndrome may
not associate with carotid plaque in subjects with
optimal, normal, or high-normal blood pressure.
Hypertension 2006; 48:411-7.
9. Ishizaka N, Matsuzaki G, Saito K, Noiri E, Mori I,
Nagai R. Expression and localization of PDGF-B,
PDGF-D, and PDGF receptor in the kidney of angiotensin II-infused rat. Lab Invest 2006; 86:1285-92.
10. Kamei N, Tobe K, Suzuki R, Ohsugi M, Watanabe
T, Kubota N, Ohtsuka-Kowatari N, Kumagai K,
Sakamoto K, Kobayashi M, Yamauchi T, Ueki K,
Oishi Y, Nishimura S, Manabe I, Hashimoto H,
Ohnishi Y, Ogata H, Tokuyama K, Tsunoda M, Ide
T, Murakami K, Nagai R, Kadowaki T. Overexpression of monocyte chemoattractant protein-1 inadipose tissues causes macrophage recruitment
and insulin resistance. J Biol Chem. 2006; 281:
26602-14.
11. Kamijo A, Sugaya T, Hikawa A, Yamanouchi M,
Hirata Y, Ishimitsu T, Numabe A, Takagi M, Hayakawa H, Tabei F, Sugimoto T, Mise N, Omata
M, Kimura K. Urinary liver-type fatty acid binding protein as a useful biomarker in chronic kidney disease. Mol Cell Biochem. 2006; 284: 17582.
12. Kawanami D, Maemura K, Takeda N, Harada T,
Nojiri T, Saito T, Manabe I, Imai Y, Nagai R.
C-reactive protein induces VCAM-1 gene expression through NF-kappaB activation in vascularendothelial cells. Atherosclerosis. 2006; 185: 3946.
13. Kishida S, Nakajima T, Ma J, Jo T, Imuta H,
Oonuma H, Iida H, Takano H, Morita T, Nagai R.
Amiodarone and N-desethylamiodarone enhanceendothelial nitric oxide production in human endothelial cells. Int Heart J. 47 2006; 47, 85-93.
14. Kusuhara K. Fujita T, Nakajima T, Sato Y, Miyagi
Y, Murakami Y, Abe T: Effects of kneeextension
exercise with KAATSU on forehead cutaneous
blood flow in healthy young and middle-aged
women. Int J KAATSU Training Res. 2006; 2:
29-34
15. Lee WH, Akatsuka S, Shirase T, Dutta KK, Jiang
L, Liu YT, Onuki J, Yamada Y, Okawa K, Wada Y,
Watanabe A, Kohro T, Noguchi N, Toyokuni S.
Alpha-tocopherol induces calnexin in renal tubu-

lar cells: another protective mechanism against
free radical-induced cellular damage. Arch Biochem Biophys. 2006; 453: 168-78.
16. Ma J, Kishida S, Wang GQ, Meguro K, Imuta H,
Oonuma H, Iida H, Jo T, Takano H, Morita T,
Nagai R, Nakajima T. Comparative effects ofazelnidipine and other Ca2+-channel blockers on
the induction of inducible nitric oxide syntahse invascular smooth muscle cells. J Cardiovasc Pharmacol. 2006; 47: 314-21.
17. Matsumura T, Matsumoto A, Ohno M, Suzuki S,
Ohta M, Suzuki E, Takenaka K, Hirata Y, Fujita T,
Nagai R. A case of cholesterol embolism confirmed by skin biopsy and successfully treatedwith statins and steroids. Am J Med Sci. 2006;
331: 280-3.
18. Matsumura T, Suzuki T, Kada N, Aizawa K,
Munemasa Y, Nagai R. Differential serum proteomic analysis in a model of metabolic disease.
Biochem Biophys Res Commun. 2006; 351: 96571.
19. Motoyama K, Fukumoto S, Koyama H, Emoto M,
Shimano H, Maemura K, Nishizawa Y. SREBP
inhibits VEGF expression in human smooth muscle cells. Biochem Biophys Res Commun. 2006;
342: 354-60.
20. Nagasaki M, Nishimura S, Ohtaki E, Kasegawa H,
Matsumura T, Nagayama M, Koyanagi T, Tohbaru
T, Misu K, Asano R, Sumiyoshi T, Hosoda S. The
echocardiographic determinants of functional mitral regurgitation differ in ischemic andnon-ischemic cardiomyopathy. Int J Cardiol.
2006; 108: 171-6.
21. Nagata D, Takahashi M, Sawai K, Tagami T, Usui
T, Shimatsu A, Hirata Y, Naruse M. Molecularmechanism of the inhibitory effect of aldosteroneon endothelial NO synthase activity. Hypertension
2006; 48: 165-71.
22. Nakajima T, Kurano M, Iida H, Takano H,
Oonuma H, Morita T, Meguro K, Sato Y, Nagata T,
KAATSU training: Results of a national survey.
Int J KAATSU Training Res. 2006; 2: 1-4.
23. Nishimura G, Manabe I, Tsushima K, Fujiu K,
Oishi Y, Imai Y, Maemura K, Miyagishi M, Higashi Y, Kondoh H, Nagai R. DeltaEF1 mediates
TGF-beta signaling in vascular smooth muscle
cell differentiation. Dev Cell. 2006; 11: 93-104.

115

24. Nishimura S, Kawai Y, Nakajima T, Hosoya Y,
Fujita H, Katoh M, Yamashita H, Nagai R, andSugiura S. Membrane potential of rat ventricular
myocytes responds to axial stretch in phase, amplitude and speed‐dependent manners. Cardiovasc Res. 2006; 72: 403-11.
25. Nishimura S, Nagai S, Sata M, Katoh M, Yamashita H, Saeki Y, Nagai R, Sugiura S. Expressionof green fluorescent protein impairs theforce-generating ability of isolated rat ventricularcardiomyocytes. Mol Cell Biochem. 2006; 286:
59-65.
26. Nishimura S, Nagai S, Katoh M, Yamashita H,
Saeki Y, Okada J, Hisada T, Nagai R,Sugiura S.
Microtubules modulate the stiffness of cardiomyocytes against shear stress. Circ Res. 2006; 98:
81-7.
27. Ohno T, Ando J, Ono M, Morita T, Motomura N,
Hirata Y, Takamoto S. The beneficial effect ofcoronary-artery-bypass surgery on survival in patients with diabetic retinopathy. Eur J Cardiothorac Surg. 2006; 30: 881-6.
28. Sahara M, Takahashi T, Morita T, Yao A, Nagashima Y, Hirata Y, Nagai R. Three-vessel coronary
artery disease complicated with congestive heart
failure in a highly aged patient with tetralogy of
Fallot having undergone palliative surgeries. Intern Med. 2006; 45: 1147-51.
29. Sahara M, Takahashi T, Imai Y, Nakajima T, Yao
A, Morita T, Hirata Y, Nagai R. New insights inthe treatment strategy for pulmonary arterial hypertension. Cardiovasc Drugs Ther. 2006; 20:377-86.
30. Sainz J, Sata M. Targeting bone marrow to treat
vascular diseases: Accelerated vascular healing bycolony stimulating factor. Cardiovasc Res. 2006;
70: 3-5.
31. Sainz J, Sata M. Maintenance of vascular homeostasis by bone marrow-derived cells. Arterioscler
Thromb Vasc Biol. 2006.; 26: 1196-7.
32. Saito K, Ishizaka N, Nagai R. How and why do
we diagnose metabolic syndrome? Ningen Dock
2006; 20: 1-5.
33. Sakamoto A, Okamoto K, Ishizaka N, Tejima K,
Hirata Y, Nagai R. 18F-fluorodeoxyglucose positron emission tomography in a case of retroperitoneal fibrosis. Int Heartl J 2006; 47: 645-50.

34. Sata M. The role of circulating vascular progenitors in angiogenesis, vascular healing and pulmonary hypertension: Lessons from animal models.
Arterioscler Thromb Vasc Biol. 2006; 26:1008-14.
35. Shimizu T, Takeda N, Takahashi M, Imai Y, Ishizaka N, Hirata Y, Nagai R. Subarachnoid hemorrhage from mycotic aneurysms. Intern Med. 2006;
45: 1189-90.
36. Takeda N, Manabe I, Iwata H, Iimuro S,
Kagechika H, Shudo K, Nagai R. Synthetic retinoid Am80 reduces scavenger receptor expression
and atherosclerosis in mice by inhibiting IL-6.
Arterioscler Thromb Vasc Biol 2006; 26: 1177-83.
37. Takeda R, Nishimatsu H, Suzuki E, Satonaka H,
Nagata D, Oba S, Sata M, Takahashi M, Yamamoto Y, Terauchi Y, Kadowaki T, Kangawa K,
Kitamura T, Nagai R, Hirata Y. Ghrelin improves
renal function in mice with ischemic acute renal
failure. J Am Soc Nephrol. 2006; 17: 113-21.
38. Terai T, Kikuchi K, Iwasawa SY, Kawabe T, Hirata Y, Urano Y, Nagano T. Modulation of luminescence intensity of lanthanide complexes byphotoinduced electron transfer and its application
to a long-lived protease probe. J Am Chem Soc.
2006; 128: 6938-46.
39. Ueki K, Oishi Y, Nishimura S, Manabe I, Hashimoto H, Ohnishi Y, Ogata H, Tokuyama K,
Tsunoda M, Ide T, Murakami K, Nagai R,
Kadowaki T. Overexpression of monocyte
chemoattractant protein-1 in adipose tissues
causes macrophage recruitment and insulin resistance. J Biol Chem. 2006; 281: 26602-14.
40. Uno K, Takenaka K, Asada K, Ebihara A, Sasaki
K, Komuro T, Nagai R, Motomura N, Ono M,
Takamoto S. Diagnosis of subacute cardiac rupture by contrast echocardiography. J Am Soc
Echocardiogr. 2006; 19: 1401 e9-1401 e11.
41. Usui S, Yao A, Hatano M, Kohmoto O, Takahashi
T, Nagai R, Kinugawa K. Upregulated neurohumoral factors are associated with left ventricularremodeling and poor prognosis in rats withmonocrotaline-induced pulmonary arterial hypertension. Circ J. 2006; 70: 1208-15.
42. Yamamoto T, Sata M, Fukuda D, Takamoto S. The
angiotensin II type 1 receptor blocker candesartan
attenuates graft vasculopathy. J Surg Res. 2006;

117

Department of Respiratory
Medicine
Professor
Takahide Nagase, M.D.,Ph.D.

Lecturer
Nobuya Ohishi, M.D.,Ph.D.,

Taiji Nagata, M.D.,Ph.D.,

Associate
Tadashi Kohyama, M.D.,Ph.D.,

Masashi Desaki, M.D.,Ph.D.,

Hitoshi Oonuma, M.D.,Ph.D.,

Yasuhiro Yamauchi, M.D.,

Go Tanaka M.D.,Ph.D.,

Reiko Okudaira M.D.,Ph.D.,

Hiroshi Kitagawa, M.D.,Ph.D.

Homepage

http://kokyuki.umin.jp/

Introduction and Organization
The staff of the Department of Respiratory Medicine, Graduate School of Medicine, University of Tokyo, consists of 1 professor, 2 lecturers, and 7 research
associates. In the University of Tokyo, affiliated hospitals and foreign institutions, approximately 50 members belong to the Department. In the University ofTokyo Hospital, about 15 respiratory physicians are
doing clinical works.
The Department of Respiratory Medicine was established in April 1998, and chaired by Professor Kazuhiko Yamamoto. In June 2003, Takahide Nagase
was appointed to Professor and since then chairs the
Department.
Based on the fact that the number of patients withrespiratory diseases such as primary lung cancer and
COPD is tremendously increasing, advancement andfruitful results of researches on respiratory medicine
are more and more expected in the 21st century. In thisera, we are conducting basic and clinical researches
for wide variety of respiratory disorders including
lung cancer, COPD, asthma and interstitial lung diseases. Especially, we have been intensively studying

the molecular mechanisms underlying the pathogenesis of lung disorders. Our research goal is to develop
novel diagnostic and therapeutic tools to manage these
pulmonary diseases.

Clinical Activities
The Department of Respiratory Medicine is responsible for the out-patient care as well as care of
in-patients (40 cases on average), which is taken at the13th floor of the hospital ward A of the University ofTokyo Hospital. Our practice is performed by thethree-member system of a junior resident, a seniorresident and an experienced associate.
Main diseases of in-patients are bronchogenic carcinoma, respiratory infections, interstitial lung diseases, COPD, and asthma. There are many emergency
visits and admission due to pneumonia , respiratory
failure, progression of lung cancer, and so on. In casesof sever respiratory failure such as ARDS, we conduct ventilatory support of such patients in collaboration with ICU staff. A specialized clinical conference
for respiratory disease has been held once a weeksince over 10 years ago, where staff of our department,

118

department of respiratory surgery and department ofradiology join and discuss together to make best diagnostic and therapeutic approach to individual patients. This conference is appreciated as prototype ofCancer Board of the University of Tokyo Hospital,
which launched this year. Our department contributes
to the pre- and post-surgical evaluation of respiratory
functions, and also receives consultation from otherdepartments.
At present, there increase highlighted interests in
respiratory medicine. Primary lung cancer is now
leading cause of cancer death, and is one of the major
medical and social problem to be overcome. In respiratory diseases, there are several disorders to which noeffective therapeutic modalities are currently available.
For example, ARDS is an acute lung injury and themortality rate for ARDS is extremely high despite ofintensive care using currently available tools. Idiopathic
pulmonary fibrosis is a progressive and fatal inflammatory disorder of the lung parenchyma, while no useful
medications are currently available to treat the disease.
We would like to make every effort to develop a noveland potential therapeutic approach to these diseases.
Number of in-patients in 2006
1. Primary lung cancer
2. Respiratory infection
3. Interstitial lung disease
4. COPD
5. Asthma

283
92
35
33
24

A weekly chart round and professor’s round arescheduled for Tuesday afternoon. A specialized clinical conference for patients with respiratory diseases isheld, together with respiratory surgeons and radiologists, where radiological diagnosis, indication ofthoracoscopic biopsy, CT-guided biopsy, and surgicaland radiological treatment are discussed, making it
possible to give best care to individual patients.

Teaching Activities
As for under-graduate education, our department
takes part in systemic lectures and specific learningfor diagnosis and treatment of respiratory diseases forthe 4th year medical students, bed-side learning for the
5th year medical students, and clinical lectures for the

5th and 6th year medical students. Clinical Clerkshipfor the 5th year students is actively performed in collaboration with expert doctors from several leading
affiliated hospitals.
In systemic lectures, comprehensive presentation
for the understanding of basic knowledge about theconcept, pathogenesis, pathology, diagnosis andtreatment of common respiratory diseases is performed.
In clinical lectures, we present clinical cases ofimportant diseases such as lung cancer, and try to
discuss with the students several important points forplanning the diagnostic evaluation and treatment incollaboration with the Faculty of the Department ofRespiratory Surgery. Recent major advance in therelevant fields are also reviewed.
During the period of bed-side learning, the students
have opportunities to experience the daily clinical carewith junior and senior residents as well as with theFaculty. Each student can learn how to make a medical interview, check physical findings and make theactual plans for the diagnosis and treatment. Several
lectures about the specific topics important in respiratory medicine such as fundamental chest radiology,
oxygen therapy are provided by the respiratory specialists.
Clinical clerkship at the 5th year of the educational
program is actively performed to facilitate the early
exposure to the clinical practice for a relatively long
period (for one month). Several lecture on the specialized theme on respiratory disease such as medical
treatment of lung cancer, are also provided. Each student is expected to learn and acquire the professionalism required for a medical doctor during this period.
Our program, in general, is highly appreciated by thestudents.
As for the post-graduate education, 8 to 9 juniorresidents join the Department of General Medicine on
the 13th floor simultaneously for one to two months,
and are expected to experience respiratory as well asother diseases. Since the training period is short, theresidents are expected to experience emergency cases
as often as possible.

Research Activities
Our department is conducting basic and clinical re-119searches for many respiratory disorders including lungcancer, COPD, asthma, interstitial lung diseases, diffuse panbronchiolitis, respiratory infections, acutelung injury, chronic respiratory failure and others. We
have also been studying the effects of air pollutants
such as diesel exhausts. Epidemiological, clinical,
cellular and molecular biological techniques are utilized for the elucidation of pathogenetic mechanisms
and for the development of novel diagnostic andtherapeutic modalities in respiratory medicine. Postgraduate students as well as the Faculty members
make considerable studies about genetic analysis oflung cancer in collaboration with the Faculty of the
Department of Respiratory Surgery, cell biologicalanalysis using airway epithelial cells, fibroblast,smooth muscle cells and genetic analysis about diffuse
panbronchiolitis. Respiratory rehabilitation utilizing
KAATSUT training shows promising preliminary results. These results have been presented and/or published in the Scientific Meeting and/or peer-review
Journals. Our main research projects are as follows.

Analysis of disease models using genetically engineered mice
Takahide Nagase is an Associate Editor of Respirology and an Editorial Board Member of American
Journal of Physiology.

References
1.

2.

3.
Molecular analysis of airway smooth muscle ionchannels
Exploration of disease-susceptibility genes in respiratory diseases
Effects of KAATSU training on respiratory rehabilitation
Analysis of DNA methylation and its clinical application in lung cancer
Analysis of signal transduction through EGF receptor
system in lung cancer and its therapeutic application
Elucidation of molecular mechanisms of diseases using conditional vectors for siRNA knockdowns
Epidemiological studies of diffuse panbronchiolitis
and interstitial lung diseases
Effects of air pollutants such as diesel exhausts on
airway hyperresponsivenessElucidation of molecular mechanisms of tissue-remodeling in respiratory diseases
Roles of chemokines, cytokines and eicosanoids onfunctional regulation of airway epithelial cells,smooth muscles and fibroblasts.
Elucidation of molecular mechanisms underlying thepathogenesis of pulmonary fibrosis
Elucidation of molecular pathogenetic mechanism ofacute lung injury

4.

5.

6.

7.

Nakajima T, Kurano M, Iida H, Takano H,
Oonuma H, Morita T, Meguro K, Sato Y, Nagata
T, Kaatsu Training Group. Use and safety of
KAATSU training: results of a national survey.
Int J KAATSU Training Res 2006;2:5-13.
Ma J, Kishida S, Wang GQ, Meguro K, Imuta H,
Oonuma H, Iida H, Jo T, Takano H, Morita T,
Nagai R, Nakajima T. Comparative effects ofazelnidipine and other Ca2+-channel blockers on
the induction of inducible nitric oxide synthase invascular smooth muscle cells. J Cardiovasc
Pharmacol 2006;47:314-21.
Kishida S, Nakajima T, Ma J, Jo T, Imuta H,
Oonuma H, Iida H, Takano H, Morita T, Nagai R.
Amiodarone and N-Desethylamiodarone Enhance
Endothelial Nitric Oxide Production in Human
Endothelial Cells. Int Heart J 2006;47:85-93.
Saito A, Motomura N, Kakimi K, Ono M, Takai
D, Sumida S, Takamoto S. Cryopreservation does
not alter the allogenicity and development ofvasculopathy in post-transplant rat aortas. Cryobiology 2006;52:251-60.
Lemière C, Ernst P, Olivenstein R, Yamauchi Y,
Govindaraju K, Ludwig MS, Martin JG, Hamid Q.
Airway inflammation assessed by invasive andnoninvasive means in severe asthma: Eosinophilic and noneosinophilic phenotypes. J Alle
Clin Immunol 2006;118:1033-1039.
Kobayashi T, Liu X, Wen FQ, Kohyama T, Shen
L, Wang XQ, Hashimoto M, Mao L, Togo S,
Kawasaki S, Sugiura H, Kamio K, Rennard SI.
Smad3 mediates TGF-beta1-induced collagen gel
contraction by human lung fibroblasts. Biochem
Biophys Res Commun 2006;339:290-5.
Sugiura H, Liu X, Kobayashi T, Togo S, Ertl RF,
Kawasaki S, Kamio K, Wang XQ, Mao L, Shen L,
Hogaboam CM, Rennard SI. Reactive nitrogenspecies augment fibroblast-mediated collagen gel

120

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10.

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13.

14.

15.

16.

contraction, mediator production, and chemotaxis.
Am J Respir Cell Mol Biol 2006;34:592-9.
Saito A, Nagayama N, Yagi O, Ohshima N, Tamura A, Nagai H, et al. Tuberculosis complicatedwith liver cirrhosis. Kekkaku 2006;81:457-65.
Okada SF, Nicholas RA, Kreda SM, Lazarowski
ER, Boucher RC. Physiological regulation of
ATP release at the apical surface of human airway epithelia. J Biol Chem 2006;281:229923002.
Fang Q, Liu X, Al-Mugotir M, Kobayashi T, Abe
S, Kohyama T, Rennard SI. Thrombin and TNFα/IL-1β Synergistically Induce Fibroblast Mediated Collagen Gel Degradation. Am J Respir
Cell Mol Biol Jul 2006;35:714-721.
Ito I, Laporte JD, Fiset PO, Asai K, Yamauchi Y,
Martin JG, Hamid Q. Downregulation of a disintegrin and metalloproteinase 33 by IFN- in
human airway smooth muscle. J Alle Clin Immunol 2007 (in press).
Sugiura H, Liu X, Togo S, Kobayashi T, Shen L,
Kawasaki S, Kamio K, Wang XQ, Mao LJ, Rennard SI. Prostaglandin E2 protects human lungfibroblasts from cigarette smoke extract-induced
apoptosis via EP2 receptor activation. J Cell
Physiol 2007 (in press).
Kamio K, Liu X, Sugiura H, Togo S, Kobayashi T,
Kawasaki S, Wang XQ, Mao L, Ahn Y, Hogaboam C, Toews ML, Rennard SI. Prostacyclin
Analogues Inhibit Fibroblast Contraction of Collagen Gels Through the cAMP-PKA Pathway.
Am J Respir Cell Mol Biol 2007 (in press).
Liu X, Das AM, Seideman J, Griswold D, Afuh
CN, Kobayashi T, Abe S, Fang Q, Hashimoto M,
Kim H, Wang X, Shen L, Kawasaki S, Rennard
SI. The CC Chemokine Ligand 2 (CCL2) Mediates Fibroblast Survival Through Interleukin-6.
Am J Respir Cell Mol Biol 2007 (in press).
Ogawa K, Saito A, Matsui H, Suzuki H, Ohtsuka
S, Shimosato D, Morishita Y, Watabe T, Niwa H,
Miyazono K. Activin-Nodal signaling is involvedin propagation of mouse embryonic stem cells. J
Cell Sci 2007 (in press).
Goto Y, Nagase T. Correspondence letter, 12-h
pretreatment with methylprednisolone versus
placebo for prevention of postextubation laryngeal oedema: a randomised double-blind trial.

17.

18.

19.

20.

21.

22.

23.

24.

Lancet 2007 (in press).
Sano A, Kage H, Sugimoto K, Kitagawa H, Aki
N, Goto A, Fukayama M, Nakajima J, Takamoto
S, Nagase T, Yatomi Y, Ohishi N and Takai D. A
second-generation profiling system for quantitative methylation analysis of multiple gene promoters: application to lung cancer. Oncogene
2007 (in press).
Sugimoto K, Kage H, Aki N, Sano A, Kitagawa
H, Nagase T, Yatomi Y, Ohishi N, Takai D. The
Induction of H3K9 Methylation by PIWIL4 at the
p16Ink4a Locus. Biochem and Biophys Res
Commun 2007 (in press).
Yamaguchi Y, Nagase T, Tomita T, Nakamura K,
Fukuhara S, Amano T, Yamamoto H, Ide Y, Suzuki M, Teramoto S, Asano T, Kangawa K, Nakagata N, Ouchi Y, Kurihara H. Beta-defensin
overexpression induces progressive muscle degeneration in mice. Am J Physiol Cell Physiol
2007 (in press).
Yamamoto H, Nagase T, Shindo T, Teramoto S,
Aoki-Nagase T, Yamaguchi Y, Yokomizo T, Nagai R, Kurihara H, Ouchi Y. Impaired innate
adrenomedullin function deteriorates airway hyperresponsiveness in mice: possible roles of allergen-induced airway wall remodeling. J Appl
Physiol 2007 (in press).
Aoki-Nagase T, Nagase T, Oh-hashi Y, Kurihara
Y, Yamaguchi Y, Yamamoto H, Nagata T, Kurihara H, Ouchi Y. Calcitonin gene-related peptide
mediates acid-induced lung injury in mice. Respirology 2007 (in press).
Tanaka G, Sandford AJ, Burkett K, Connett JE,
Anthonisen NR, Pare PD, He JQ. Tumour necrosis factor and lymphotoxin A polymorphisms andlung function in smokers. Eur Respir J 2007 (inpress).
Tanaka G, Shojima J, Matsushita I, Nagai H,
Kurashima A, Nakata K, Toyota E, Kobayashi N,
Kudo K, Keicho N. Pulmonary Mycobacterium
avium complex infection: Association with
NRAMP1 polymorphisms. Eur Respir J 2007 (inpress).
Nakajima T, Takano H, Kurano M, Iida H, Kubota N, Yasuda T, Kato M, Meguro K, Sato Y,
Yamazaki Y, Kawashima S, Ohshima H, Tachibana S, Nagata T, Abe T, Ishii N, Morita T. Ef-

121fects of KAATSU training on haemostasis in
healthy subjects. Int J KAATSU Training Res
2007 (in press).

122

Department of Gastroenterology
Professor
Masao Omata, M.D., Ph.D.

LecturerHaruhiko Yoshida, M.D., Ph.D.

Shuichiro Shiina, M.D., Ph.D.

Minoru Tada, M.D., Ph.D.

Associate
Hiroshi Kanamori, M.D., Ph.D.
Hiroshi Mitsui, M.D., Ph.D.
Hirosato Mashima, M.D., Ph.D.
Yutaka Yamaji, M.D., Ph.D.
Masao Akanuma, M.D., Ph.D.
Hiroyuki Isayama, M.D., Ph.D.
Takeshi Tsujino, M.D., Ph.D.
Tadashi Goto, M.D., Ph.D.
Naoki Sasahira, M.D., Ph.D.
Ryosuke Tateishi, M.D., Ph.D.

Homepage

Tomoaki Tomiya, M.D., Ph.D.
Naoya Kato, M.D., Ph.D.
Keisuke Hamamura, M.D., Ph.D.
Goichi Togo, M.D., Ph.D.
Hajime Fujie, M.D., Ph.D.
Hideo Yoshida, M.D., Ph.D.
Hideaki Ijichi, M.D., Ph.D.
Mitsuhiro Fujishiro, M.D., Ph.D.
Kenji Hirano, M.D., Ph.D.

http://www.h.u-tokyo.ac.jp/gastro/

Introduction and Organization

Clinical Activities

The Department of Gastroenterology was established through a reorganization of the Postgraduate
School of Medicine and that of the Division of Internal Medicine of the University of Tokyo Hospital in
1998. The department is responsible for clinical services, education and research activities in the field of
liver, pancreatobiliary and digestive canal. It is now
comprised of a professor, 3 lecturers, 19 associates, 7
fellows, 34 graduates and 11 other visiting researchers
including students from abroad. A number of others
are under a temporary transfer in and outside thecountry. The north and south wings on the 11th floorof Ward A have provided core hospital rooms for the
department. At present, forth and fifth floor of Ward B
also takes important part for providing rooms of inpatients. Laboratories of department are scattered ineach floor, mainly of Clinical Research Center andFirst Research Building as in the other departments.

The Department of Gastroenterology is in charge ofabout 80-100 inpatients on average, which is about
2,300 in total per year. We receive about 90 new patients in and out of the hospital each week, with anaverage hospital stay of 12 days. Resident, junior andsenior staff members bear the responsibility for a
medical management of each inpatient, in collaboration with subspecialty groups concerned. The staff
members examine about 5,000 outpatients with various digestive diseases in a month. Professor’s ward
round is performed on Monday and Wednesday
mornings. Specialty and subspecialty clinical conferences are held on Monday evening.
Hepatocellular carcinoma has the largest number ofcases (750 inpatients in 2006). Hepatocellular carcinoma treatments, represented by percutaneous radiofrequency ablation, have in excess of 2,500 cases encounters per year, showing one of the greatest

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achievements in the field. Also, performing radiofrequency ablation for metastatic liver tumors has remarkable increase in recent years (134 inpatients in2006). Stages of chronic liver disease progression has
conventionally relied on liver biopsy until in recent
years of the introduction of Fibro scan, which helps tomeasure stiffness of liver by ultrasound. ERCP is performed in excess of 600 cases each year. Patientstreated for choledocholithiasis with endoscopic papillary balloon dilation method exceed 1,200, which ispossibly the largest numbers in the world. Endoscpic
metallic stenting is an effective palliative care for malignant obstructive jaundice (60 patients a year). Covered metallic stent placement has been performed in a
total of 300 cases, which may be the world’s largest
number. Pancreatic interventions such as pancreatic
stenting, cystic drainage, endoscopic stone extraction
and lithotripsy using ESWL (extracorporeal shockwave lithotripsy) are also performed for many challenging cases. ESD (endoscopic submucosal dissection) is performed as a curative endoscopic treatment
for neoplasms in esophagus, stomach or colon (210patients a year). Endoscopic variceal ligations foresophageal varices (50 patients a year) are also frequently done. Double-ballon endoscopy and capsuleendoscopy have been introduced recently, which enabled the examination of whole small intestines. All
those interventions are performed by members of thedepartment specially trained for each technique. Our
strategy for the management of malignancies is interventional therapy and chemotherapy (pancreatobiliary; 94 cases and digestive tract; 60 cases).
On outpatient basis, ultrasonography is performed
on 9,700 patients, gastroduodenal endoscopy on 5,200,
and colonoscopy on 3,000 patients each year, leading
the detection of about 130 cases of gastric cancer and160 cases of colorectal cancer annually. About 40 %of them are treated endoscopically, but we also aim to
perform basic studies using specimen, and turn these
efforts to clinical activities.

Educational Activities
Systematic and clinical lectures on gastroenterology
are regularly given to undergraduate medical students
by staff members of the department. In addition, several courses of practical teaching are provided for the

students. In particular, the Department of Gastroenterology makes much of the importance of bed-side
teaching for the fifth grade students, where each student is allotted to an inpatient by joining the group ofphysicians and offering the opportunity to learn digestive diseases practically. The results are reported to theprofessor at the end of the course as an oral examination. Students are also required to summarize and outline articles in world’s leading medical journals.
Residents of internal medicine join the Department
of Gastroenterology for 1-6 months in rotation in theirfirst year as a doctor, where they learn therapeutics
and diagnostics in gastroenterology together withgeneral internal medicine. Giving presentations at thescientific meeting is highly encouraged. If they areinterested in gastroenterology in particular, they may
learn advanced techniques in gastroenterology in affiliated hospitals for a few years. Usually, they will
come back to the department after that period, andimprove their clinical skills still further while at theeducation course. The majority of them also become
graduate student, and starts medical researches either
as a basic or clinical researcher. Currently, the department has 50 students who were graduated from
more than 30 medical schools in Japan.

Research Activities
Since gastroenterology covers various organs anddiseases, everything below the diaphragms except for
the kidneys and the reproductive system, themes of a
research are virtually unlimited as shown in the list of
publication described below. Both basic and clinicalresearchers are equally encouraged, on condition thatthe results may eventually contribute to the cure ofgastroenterological disorders. For basic researches,the department has been eager to acquire cutting-edge
methodologies, especially those in molecular biology
and genetics. The themes of our recent basic researches include mRNA expression analysis using
microarray, protein expression analysis using mass
spectrometer, and gene mutation analysis using laser
micro dissection of clinically obtained samples. Various clinical activities are recorded in database andanalyzed. Studies oriented for evidence-based medicine are highly appreciated. Recent randomized-controlled trials include interferon to prevent

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recurrence of hepatocellular carcinoma, evaluation ofdiagnostic usefulness of angiography with computed
tomography, and radiofrequency ablation for liver
metastasis of colorectal cancer. We have also designed
clinical trials of TSU-68 for advanced hepatocellular
carcinoma, erythropoietin for anemia introduced byinterferon with ribavirin therapy, TS-1 alone or combined with gemcitabine for pancreatic and bile duct
cancers.
The department is dedicated to pursuing bettermedical services from all facets of the subspecialty ofgastroenterology, which is brought about by both basic
and clinical researches.

References
1. Akamatsu M, Yoshida H, Shiina S, Teratani T, Obi
S, Tateishi R, Mine N, Kondo Y, Kawabe T,
Omata M. Sustained viral response prolonged
survival of patients with C-viral hepatocellular
carcinoma. Liver Int 2006; 26: 536-542. Sustained
viral re-sponse prolonged survival of patients with
C-viral hepatocellular carcinoma. Liver Int 2006;
26: 536-542.
2. Chang TT, Jia JD, Omata M, Yoon SK. New
thera-pies for chronic hepatitis B infection. Liver
Int 2006 ; 26 : S30-S37.
3. Dharel N, Kato N, Muroyama R, Moriyama M,
Shao RX, Kawabe T, Omata M. MDM2 promoter
SNP309 is associated with the risk of hepatocellular carcinoma in patients with chronic hepatitis
C. Clin Cancer Res 2006 ; 12 : 4867-4871.
4. Enomoto S, Yahagi N, Fujishiro M, Oka M,
Kaku-shima N, Iguchi M, Isayama H, Yanaoka K,
Arii K, Tamai H, Shimizu Y, Ichinose M, Omata
M. He-mosuccus pancreaticus: Clearly identified
by timely duodenoscopy, multiplanar volume reformation of CT image and celiac angiography.
JAMJ 2006; 49: 128-131.
5. Fujishima T, Ishikawa T, Shiratori Y, Kanda M,
Tateishi R, Akamatsu M, Koike Y, Sato S, Obi S,
Hamamura K, Teratani T, Shiina S, Yoshida H,
Kawabe T, Omata M. Age-related comparison of
the profiles of patients with Hepatocellular carcinoma. Hepatogastroenterology 2006 ; 53 : 913918.
6. Fujishiro M, Oka M, Yahagi N, Nakamura M,

Ka-kushima N, Kodashima S, Kobayashi K,
Hashimoto T, Yamamichi N, Moriyama Y, Tateishi
A, Ono S, Shimizu Y, Ichinose M, Miki K, Omata
M. Correla-tion of serum pepsinogens and grossappearances combined with histologyin early gastric cancer. J Exp Clin Cancer Res 2006 ; 25 :207-212.
7. Fujishiro M, Yahagi N, Kakushima N, Kodashima
S, Ichinose M, Omata M. En bloc resection of alarge semicircular esophageal cancer by endoscopic submucosal dissection. Surg Laparosc Endosc Per-cutan Tech 2006 ; 16 : 237-241.
8. Fujishiro M, Yahagi N, Kakushima N, Kodashima
S, Ichinose M, Omata M. Successful endoscopic
en bloc resection of a large laterally spreading
tumor in the rectosigmoid junction by endoscopic
submuco-sal dissection. Gastrointest Endosc
2006; 63 : 178-183.
9. Fujishiro M, Yahagi N, Kakushima N, Kodashima
S, Muraki Y, Ono S, Kobayashi K, Hashimoto T,
Ya-mamichi N, Tateishi A, Shimizu Y, Oka M,
Ogura K, Kawabe T, Ichinose M, Omata M. Successful non-surgical management of perforation
complicating endoscopic submucosal dissection ofgastrointesti-nal epithelial neoplasms. Endoscopy
2006; 38: 1001-1006.
10. Fujishiro M, Yahagi N, Kakushima N, Kodashima
S, Muraki Y, Ono S, Yamamichi N, Tateishi A,
Shi-mizu Y, Oka M, Ogura K, Kawabe T, Ichinose
M, Omata M. Endoscopic submucosal dissectionof esophageal squamous cell neoplasms. Clin
Gastro-enterol Hepatol 2006; 4 : 688-694.
11. Fujishiro M, Yahagi N, Nakamura M, Kakushima
N, Kodashima S, Ono S, Kobayashi K, Hashimoto
T, Yamamichi N, Tateishi A, Shimizu Y, Oka M,
Ogura K, Kawabe T, Ichinose M, Omata M.
Suc-cessful outcomes of a novel endoscopic
treatment for GI tumors: endoscopic submucosal
dissection with a mixture of high-molecularweight hyaluronic acid, glycerin, and sugar. Gastrointest Endosc 2006 ; 63 : 243-249.
12. Fujishiro M, Yahagi N, Nakamura M, Kakushima
N, Kodashima S, Ono S, Kobayashi K, Hashimoto
T, Yamamichi N, Tateishi A, Shimizu Y, Oka M,
Ogura K, Kawabe T, Ichinose M, Omata M. Endoscopic submucosal dissection for rectal epithelial
neoplasia. Endoscopy 2006; 38: 493-497.

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13. Fujishiro M, Yahagi N, Nakamura M, Kakushima
N, Kodashima S, Ono S, Kobayashi K, Hashimoto
T, Yamamichi N, Tateishi A, Shimizu Y, Oka M,
Ichi-nose M, Omata M. Safety of argon plasma
coagula-tion for hemostasis during endoscopic
mucosal re-section. Surg Laparosc Endosc Percutan Tech 2006 ; 16 : 137-140.
14. Fujishiro M, Yahagi N, Nakamura M, Kakushima
N, Kodashima S, Ono S, Kobayashi K, Hashimoto
T, Yamamichi N, Tateishi A, Shimizu Y, Oka M,
Ichi-nose M, Omata M. Submucosal injection of
normal saline may prevent tissue damage fromargon plasma coagulation: an experimental study
using resected porcine esophagus, stomach, andcolon. Surg Laparosc Endosc Percutan Tech
2006 ; 16 : 307-311.
15. Fujiwara K, Yokosuka O, Komine F, Moriyama M,
Kato N, Yoshida H, Tanaka N, Imazeki F, Shiratori Y, Arakawa Y, Omata M; for Tokyo Hepatitis
Net-work. Twenty-four weeks of interferon alpha-2b in combination with ribavirin for Japanesehepatitis C patients: sufficient treatment period forpatients with genotype 2 but not for patients withgenotype 1. Liver Int 2006; 26 : 520-528.
16. Guleng B, Tateishi K, Ohta M, Asaoka Y, Jazag A,
Lin LJ, Tanaka Y, Tada M, Seto M, Kanai F,
Kawabe T, Omata M. Smoothened gene mutations
found in digestive cancer have no aberrant
Hedge-hog signaling activity. J Gastroenterol2006 ; 41 : 1238-1239.
17. Hanajiri K, Maruyama T, Kaneko Y, Mitsui H,
Wa-tanabe S, Sata M, Nagai R, Kashima T, Shibahara J, Omata M, Matsumoto Y. Microbubble-induced in-crease in ablation of liver tumors
by high-intensity focused ultrasound. Hepatol Res
2006; 36: 308-314.
18. Hirano K, Kawabe T, Komatsu Y, Matsubara S,
Togawa O, Arizumi T, Yamamoto N, Nakai Y,
Sa-sahira N, Tsujino T, Toda N, Isayama H, Tada
M, Omata M. High-rate pulmonary involvementin autoimmune pancreatitis. Intern Med J 2006 ;36 : 58-61.
19. Hirano K, Kawabe T, Yamamoto N, Nakai Y,
Sasa-hira N, Tsujino T, Toda N, Isayama H, Tada
M, Omata M. Serum IgG4 concentrations in pancreatic and biliary diseases. Clin Chim Acta 2006;
367 : 181-184.

20. Hirata Y, Maeda S, Ohmae T, Shibata W, Yanai A,
Ogura K, Yoshida H, Kawabe T, Omata M.
Helico-bacter pylori induces IkappaB kinase alphanuclear translocation and chemokine production
in gastric epithelial cells. Infect Immun 2006; 74:1452-1461.
21. Hirata Y, Ohmae T, Shibata W, Maeda S, Ogura K,
Yoshida H, Kawabe T, Omata M. MyD88 and
TNF receptor-associated factor 6 are critical signal transducers in helicobacter pylori-Infected
human epithelial cells. J Immunol 2006; 176:3796-3803.
22. Ikai I, Takayasu K, Omata M, Okita K, Nakanuma
Y, Matsuyama Y, Makuuchi M, Kojiro M, Ichida T,
Arii S, Yamaoka Y; for the Liver Cancer Study
Group of Japan. A modified Japan Integrated
Stage score for prognostic assessment in patientswith hepatocellular carcinoma. J Gastroenterol
2006; 41 : 884-892.
23. Ikeda H, Nagashima K, Yanase M, Tomiya T, Arai
M, Inoue Y, Tejima K, Nishikawa T, Watanabe N,
Kitamura K, Isono T, Yahagi N, Noiri E, Inao M,
Mochida S, Kume Y, Yatomi Y, Nakahara K,
Omata M, Fujiwara K. The herbal medicine
inchin-ko-to (TJ-135) induces apoptosis in cultured rat hepatic stellate cells. Life Sci 2006; 78:2226-2233.
24. Isayama H, Kawabe T, Nakai Y, Tsujino T, Sasahira N, Yamamoto N, Arizumi T, Togawa O, Matsubara S, Ito Y, Sasaki T, Hirano K, Toda N, Komatsu Y, Tada M, Yoshida H, Omata M. Cholecystitis after metallic stent placement in patientswith malignant distal biliary obstruction. Clin
Gastroenterol Hepa-tol 2006; 4: 1148-1153.
25. Kamijo A, Sugaya T, Hikawa A, Yamanouchi M,
Hirata Y, Ishimitsu T, Numabe A, Takagi M, Hayakawa H, Tabei F, Sugimoto T, Mise N, Omata
M, Kimura K. Urinary liver-type fatty acid binding protein as a useful biomarker in chronic kidney disease. MOLECULAR AND CELLULAR
BIOCHEMISTRY 2006; 284: 175-182.
26. Kakushima N, Fujishiro M, Kodashima S, Kobaya-shi K, Tateishi A, Iguchi M, Imagawa A,
Motoi T, Yahagi N, Omata M. Histopathologic
characteristics of gastric ulcers created by endoscopic submucosal dissection. Endoscopy 2006;
38 : 412-415.

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27. Kakushima N, Fujishiro M, Kodashima S, Muraki
Y, Tateishi A, Omata M. A learning curve forendo-scopic submucosal dissection of gastricepithelial neoplasms. Endoscopy 2006 ; 38 : 991995.
28. Kakushima N, Fujishiro M, Yahagi N, Kodashima
S, Nakamura M, Omata M. Helicobacter pylori
status and the extent of gastric atrophy do not affect ulcer healing after endoscopic submucosal
dissection. J Gastroenterol Hepatol 2006; 21:1586-1589.
29. Kakushima N, Yahagi N, Fujishiro M, Kodashima
S, Nakamura M, Omata M. Efficacy and safety ofendoscopic submucosal dissection for tumors of
the esophagogastric junction. Endoscopy 2006;
38: 170-174.
30. Kodashima S, Fujishiro M, Takubo K, Kammori
M, Nomura S, Kakushima N, Muraki Y, Tateishi A,
Kaminishi M, Omata M. Ex-vivo study ofhigh-magnification chromoendoscopy in the gastrointestinaltract to determine the optimal staining
conditions for endocytoscopy. Endoscopy 2006;
38: 1115-1121.
31. Kodashima S, Fujishiro M, Yahagi N, Kakushima
N, Ichinose M, Omata M. Endoscopic submucosal
dissection for gastric neoplasia: experience withthe flex-knife (Review). Acta Gastroenterol Belg
2006; 69: 224-229.
32. Kodashima S, Fujishiro M, Yahagi N, Kakushima
N, Omata M. Endoscopic submucosal dissection
using flexknife. J Clin Gastroenterol 2006; 40:
378-384.
33. Kondo Y, Yoshida H, Shiina S, Tateishi R, Teratani T, Omata M. Artificial ascites technique for
per-cutaneous radiofrequency ablation of livercancer adjacent to the gastrointestinal tract. Br J
Surg 2006; 93: 1277-1282.
34. Locarnini S, Omata M. Molecular virology ofhepa-titis B virus and the development of antiviraldrug resistance. Liver Int 2006; 26: S11-S22.
35. Muroyama R, Kato N, Yoshida H, Otsuka M,
Mo-riyama M, Wang Y, Shao RX, Dharel N, Tanaka Y, Ohta M, Tateishi R, Shiina S, Tatsukawa
M, Fukai K, Imazeki F, Yokosuka O, Shiratori Y,
Omata M. Nucleotide change of codon 38 in the X
gene of hepatitis B virus genotype C is associatedwith an increased risk of hepatocellular carcinoma.

J Hepa-tol 2006; 45: 805-812.
36. Obi S, Yoshida H, Toune R, Unuma T, Kanda M,
Sato S, Tateishi R, Teratani T, Shiina S, Omata M.
Combination therapy of intraarterial 5fluorouracil and systemic interferon-alpha for advanced hepato-cellular carcinoma with portal venous invasion. Cancer 2006; 106 : 1990-1997.
37. Ogura M, Yamaji Y, Hikiba Y, Maeda S, Matsumura M, Okano K, Sassa R, Yoshida H, Kawabe T,
Omata M. Gastric cancer among peptic ulcer
pa-tients: Retrospective, long-term follow-up. Dig
Liver Dis 2006; 38: 811-814.
38. Shibata W, Hirata Y, Maeda S, Ogura K, Ohmae T,
Yanai A, Mitsuno Y, Yamaji Y, Okamoto M,
Yo-shida H, Kawabe T, Omata M. CagA protein
se-creted by the intact type IV secretion system
leads to gastric epithelial inflammation in the
Mongolian gerbil model. J Pathol 2006; 210:306-314.
39. Tada M, Kawabe T, Arizumi M, Togawa O, Matsu-bara S, Yamamoto N, Nakai Y, Sasahira N,
Hirano K, Tsujino T, Tateishi K, Isayama H, Toda
N, Yo-shida H, Omata M. Pancreatic cancer in patients with pancreatic cystic lesions: a prospective
study in 197 patients. Clin Gastroenterol Hepatol
2006; 4: 1265-1270.
40. Takayasu K, Arii S, Ikai I, Omata M, Okita K,
Ichida T, Matsuyama Y, Nakanuma Y, Kojiro M,
Makuuchi M, Yamaoka Y; Liver Cancer Study
Group of Japan. Prospective cohort study oftran-sarterial chemoembolization for unresectablehepa-tocellular carcinoma in 8510 patients. Gastroen-terology 2006; 131: 461-469.
41. Takikawa Y, Endo R, Suzuki K, Fujiwara K,
Omata M; Fulminant Hepatitis Study Group ofJapan. Pre-diction of hepatic encephalopathy development in patients with severe acute hepatitis.
Dig Dis Sci 2006; 51: 359-364.
42. Tanaka Y, Kanai F, Ichimura T, Tateishi K, Asaoka
Y, Guleng B, Jazag A, Ohta M, Imamura J,
Ikenoue T, Ijichi H, Kawabe T, Isobe T, Omata M.
The hepatitis B virus X protein enhances AP-1 activa-tion through interaction with Jab1. Oncogene
2006; 25: 633-642.
43. Tanaka Y, Kanai F, Tada M, Asaoka Y, Guleng B,
Jazag A, Ohta M, Ikenoue T, Tateishi K, Obi S,
Kawabe T, Yokosuka O, Omata M. Absence of127

PIK3CA hotspot mutations in hepatocellular
carci-noma in Japanese patients. Oncogene 2006;
25: 2950-2952.
44. Tateishi K, Ohta M, Guleng B, Kanai F, Tanaka Y,
Asaoka Y, Jazag A, Imamura J, Imamura T, Ijichi
H, Ikenoue T, Kawakami T, Fukushima Y,
Washida M, Sata M, Miyagishi M, Taira K, Yoshida H, Kawabe T, Omata M. TRAIL-induced
cell death cooperates with IFN-gamma activationin the graft-versus-tumor effect against colon tumors. Int J Cancer 2006; 118: 2237-2246.
45. Tateishi K, Ohta M, Kanai F, Guleng B, Tanaka Y,
Asaoka Y, Tada M, Seto M, Jazag A, Lianjie L,
Okamoto M, Isayama H, Tada M, Yoshida H,
Kawabe T, Omata M. Dysregulated expression ofstem cell factor Bmi1 in precancerous lesions of
the gastrointestinal tract. Clin Cancer Res 2006;
12: 6960-6966.
46. Tateishi R, Shiina S, Yoshida H, Teratani T, Obi S,
Yamashiki N, Yoshida H, Akamatsu M, Kawabe T,
Omata M. Prediction of recurrence of hepatocellu-lar carcinoma after curative ablation using
three tumor markers. Hepatology 2006; 44: 15181527.
47. Teratani T, Yoshida H, Shiina S, Obi S, Sato S,
Tateishi R, Mine N, Kondo Y, Kawabe T, Omata
M. Radiofrequency ablation for hepatocellular
carci-noma in so-called high-risk locations.
Hepatology 2006; 43: 1101-1108.
48. Tsujino T, Isayama H, Sugawara Y, Sasaki T,
Kogure H, Nakai Y, Yamamoto N, Sasahira N,
Ya-mashiki N, Tada M, Yoshida H, Kokudo N,
Kawabe T, Makuuchi M, Omata M. Endoscopic
manage-ment of biliary complications after adultliving do-nor liver transplantation. Am J Gastroenterol 2006; 101 : 2230-2236.
49. Wang Y, Kato N, Jazag A, Dharel N, Otsuka M,
Taniguchi H, Kawabe T, Omata M. Hepatitis C
vi-rus core protein is a potent inhibitor of RNA
si-lencing-based antiviral response. Gastroenterology 2006 ; 130 : 883-892.
50. Watabe H, Yamaji Y, Okamoto M, Kondo S, Ohta
M, Ikenoue T, Kato J, Togo G, Matsumura M,
Yo-shida H, Kawabe T, Omata M. Risk assessment for delayed hemorrhagic complication ofcolonic poly-pectomy: polyp-related factors andpatient-related factors. Gastrointest Endosc 2006;

64: 73-78.
51. Yamaji Y, Mitsushima T, Ikuma H, Watabe H,
Okamoto M, Yoshida H, Kawabe T, Wada R,
Omata M. Right-side shift of colorectal adenomas
with aging. Gastrointest Endosc 2006; 63: 453458.
52. Yamaji Y, Mitsushima T, Yoshida H, Watabe H,
Okamoto M, Wada R, Ikuma H, Kawabe T, Omata
M. The malignant potential of freshly developed
colorectal polyps according to age. Cancer
Epide-miol Biomarkers Prev 2006; 15: 24182421.
53. Yamamoto N, Nakai Y, Sasahira N, Hirano K,
Tsu-jino T, Isayama H, Komatsu Y, Tada M, Yoshida H, Kawabe T, Hiki N, Kaminishi M, Kurosaka H, Omata M. Efficacy of peppermint oil as
an anti-spasmodic during endoscopic retrograde
cholan-giopancreatography.
J
Gastroenterol
Hepatol 2006; 21: 1394-1398.
54. Yamashiki N, Sugawara Y, Tamura S, Kaneko J,
Nojiri K, Omata M, Makuuchi M. Selection ofliver-transplant candidates for adult-to-adult living donor liver transplantation as the only surgical
op-tion for end-stage liver disease. Liver Transpl
2006; 12: 1077-1083.
55. Yamashita H, Nakagawa K, Shiraishi K, Tago M,
Igaki H, Nakamura N, Sasano N, Shiina S, Omata
M, Ohtomo K. External beam radiotherapy totreat intra- and extra-hepatic dissemination ofhepato-cellular carcinoma after radiofrequency
thermal ab-lation. J Gastroenterol Hepatol 2006;
21: 1555-1560.
56. Yamazaki T, Suzuki J, Shimamoto R, Tsuji T,
Ohmoto Y, Toyo-Oka T, Omata M, Ohtomo K,
Nagai R. Focalized contractile impairment at
hy-pertrophied myocardium proven in consideration of wall stress in patients with hypertrophic
cardio-myopathy. INTERNATIONAL HEARTJOURNAL2006; 47: 247-258.
57. Yoshida H, Shiratori Y, Omata M. Step-wise
pro-gression of fibrosis toward hepatocellular
carci-noma and its resolution. In:Schinazi RF,
Schiff ER, eds. Framing the Knowledge of
Therapeutics for Viral Hepatitis. Georgia:IHL
Press. 2006: 29-40.
58. Yoshikumi Y, Mashima H, Suzuki J, Yamaji Y,
Okamoto M, Ogura K, Kawabe T, Omata M. A

128case of rectal Dieulafoy's ulcer and successful
en-doscopic band ligation. Can J Gastroenterol
2006; 20: 287-290.

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Department of Nephrology and
Endocrinology
Professor
Toshiro Fujita, M.D.,Ph.D.

Associate Professor
Tomoki Okazaki, M.D.,Ph.D.,

Katsuyuki Ando, M.D., Ph.D.,

Keiichi Hishikawa, M.D.,Ph.D.,

Shinya Kaname, M.D.,Ph.D.,

Takanari Gotoda M.D.,Ph.D.,

Lecturer
Seiji Fukumoto, M.D., Ph.D.,

George Seki, M.D., Ph.D.,

Eisei Noiri, M.D., Ph.D.,

Akihiro Tojo, M.D., Ph.D.,

Hospital Lecturer
Taroh Iiri, M.D., Ph.D.,

Koji Takano, M.D., Ph.D.,

Masaomi Nangaku, M.D., Ph.D.

Associate
Etsu Suzuki, M.D., Ph.D.,
Masashi Isshiki, M.D., Ph.D.,
Takeshi Marumo, M.D., Ph.D.,
Yugo Shibagaki, M.D., Ph.D.,
Junichi Hirahashi, M.D., Ph.D.,
Hideomi Yamada, M.D., Ph.D.,
Yoshitaka Ishibashi, M.D., Ph.D.

Homepage

Katsutoshi Takahashi, M.D., Ph.D.,
Shigeyoshi Oba, M.D., Ph.D.,
Miki Nagase, M.D., Ph.D.,
Noriko Makita, M.D., Ph.D.,
Yuichi Hori, M.D., Ph.D.,
Takehiko Wada, M.D., Ph.D.

http://plaza.umin.ac.jp/~kid-endo/top.html

Introduction and Organization
The Division of Nephrology and Endocrinology is
one of the major divisions in the Department of Internal Medicine of the University of Tokyo, which covers
nephrology, hypertension, and endocrinology, and also
renal diseases associated with diabetes mellitus, cardiovascular diseases, collagen diseases and so on. We
have 18 proper beds on the 12th floor of the Northernpart of Ward A in the Tokyo University Hospital, andten beds for hemodialysis. Usually we have up to 30

inpatients in the hospital. The Professor and eachmember of the staff have an active responsibility for
all clinical activities. Each member has an office and a
research laboratory. In our department, almost all
members support the clinical works of our residents,and other 2 associates are involved mainly in the Hemodialysis Unit. We are intimately working together
in all clinical activities under the supervision of theProfessor and the Associate Professors.

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Clinical activities
The residents are in charge of up to 30 patients ofour division and supervised by associates and faculty
staffs. Every Tuesday, we have a clinical conference todiscuss the diagnosis and treatment of our patientswith all members of the staff. Particularly difficult
cases are further discussed with guest specialists fromoutside almost once a month.
Nephritis should be morphologically diagnosed byrenal biopsy and the optimal treatment should be chosen for each patient. In our division, renal biopsy isactively performed to give the real benefits of treatment to the patients. We also treat diabetic patientswith proteinuria and end-stage renal failure. Each staffof our division also works at the hemodialysis unit,
thus we can manage patients in every stage of renal
disease.
In the endocrine unit there is a variety of patients
having disorders in thyroid, parathyroid, pituitary,adrenal and genital glands. It is also our specialty todiagnose and treat secondary hypertension caused byprimary aldosteronism, Cushing’s syndrome, pheochromocytoma, renal artery stenosis and so on. We
often have consultation from other divisions concerning disorders of water and mineral metabolism.

Education
We have responsibility for educating undergraduate,
graduate students and residents. Our stuffs take part inseveral lectures for undergraduate and graduate students. In addition, our members are actively involved
in bed-side learning and clinical clerkship of undergraduate students, and other clinical practice. In theward, we are also educating residents during dailyclinical works and periodical lectures concerning kidney and endocrine diseases.

Research
In our department there are more than 30 studentsof the Graduate School. We have research conferences
every Tuesday, to discuss the results of the researchwith the Professor and faculty members. As you see inthe references below, our research topics are various
and cover every field of Nephrology, Hypertension

and Endocrinology. We are also actively collaboratingwith scientists outside the division and outside theUniversity including foreign countries. Achievementsof our researches are published in world top level
journals of Nephrology, Hypertension and Endocrinology.

Publications
1. Ando K, Fujita T. Control of morning bloodpressure: The best preventive strategy against
stroke. Hypertens Res 2006;29:555-556.
2. Doi K, Okamoto K, Negishi K, Suzuki Y, Nakao
A, Fujita T, Toda A, Yokomizo T, Kita Y, Kihara
Y, Ishii S, Shimizu T, Noiri E. Attenuation of folic acid-induced renal inflammatory injury inplatelet-activating factor receptor-deficient mice.
Am J Pathol 2006;168:1413-1424.
3. Doi K, Noiri E, Nakao A, Fujita T, Kobayashi S,
Tokunaga K. Functional polymorphisms in thevascular endothelial growth factor gene are associated with development of end-stage renal disease in males. J Am Soc Nephrol 2006;17:823830.
4. Dominguez JH, Wu P, Hawes JW, Deeg M,
Walsh J, Packer SC, Nagase M, Temm C, Goss E,
Peterson R. Renal injury similarities and differences in male and female rats with the metabolic
syndrome. Kidney Int 2006;69:1969-1976.
5. Hishikawa K, Fujita T. Stem cells and kidneydisease. Hypertens Res 2006;29:745-749.
6. Katevetin P, Miyata T, Inagi R, Tanaka T, Sassa
R, Ingelfinger JR, Fujita T, Nangaku M. Highglucose blunts VEGF response to hypoxia via theoxidative stress-regulated HIF-HRE pathway. J
Am Soc Nephrol, 2006;17:1405-1413.
7. Marumo T, Uchimura H, Hayashi M, Hishikawa K,
Fujita T. Aldosterone impairs bone marrowderived progenitor cell formation. Hypertension
2006;48:490-496.
8. Matsui H, Shimosawa T, Uetake Y, Wang H,
Ogura S, Kaneko T, Liu J, Ando K, Fujita T. Protective effect of potassium against the hypertensive cardiac dysfunction. Hypertension. 2006;48:
225-231.
9. Nagase M, Shibata S, Yoshida S, Nagase T, Gotoda T, Fujita T. Podocyte injury underlies the132

glomerulopathy of Dahl salt-hypertensive rats andis reversed by aldosterone blocker. Hypertension
2006;47:1084-1093.
10. Nagase M, Yoshida S, Shibata S, Nagase T, Gotoda T, Ando K, Fujita T: Enhanced aldosterone
signaling in the early nephropathy of rats withmetabolic syndrome: possible contribution of
fat-derived factors. J Am Soc Nephrol 2006;17:3438-3446.
11. Nangaku M. Chronic hypoxia and tubulointerstitial injury. A final common pathway to end stage
renal failure. J Am Soc Nephrol 2006;17:17-25.
12.Nishi H, Hanafusa N, Kondo Y, Nangaku M, Sugawara Y, Makuuchi M, Noiri E, Fujita T. Clinical outcome of thrombotic microangiopathy after
living-donor liver transplantation treated withplasma exchange therapy. Clin J Am Soc Nephrol
2006;1:811-819.
13. Ohse T, Inagi R, Tanaka T, Ota T, Miyata T, Kojima I, Ingelfinger JR, Ogawa S, Fujita T, Nangaku M. Albumin induces endoplasmic reticulum(ER) stress and apoptosis in renal proximal tubular cells. Kidney Int 2006;70:1447-1455.
14. Okamoto K, Kobayashi S, Noiri E. Longer treatment time and slower ultrafiltration in hemodialysis: associations with reduced mortality in the Dialysis Outcomes and Practice Patterns Study.
Kidney Int 2006;70:1877.
15. Sekine N, Takano K, Kimata-Hayashi N, Kadowaki T, Fujita T. Adrenomedullin inhibits insulin
exocytosis
via
pertussis
toxin-sensitive
G-protein-coupled mechanism. Am J Physiol
2006;291:E9-E14.
16. Shibata S, Nagase M, Fujita T. Fluvastatin ameliorates podocyte injury in proteinuric rats via
modulation of excessive Rho signaling. J Am Soc
Nephrol 2006;17:754-764.
17. Shimizu H, Ishibashi Y, Kumagai T, Kawarazaki
H, Kawarazaki W, Kaname S, Fujita T. Successful
reinstitution of peritoneal dialysis after gastric resection: a case report. Perit Dial Int 2006;26:509-510.
18. Shimizu M, Ishibashi Y, Taki F, Shimizu H, Hirahara I, Kaname S, Fujita T. ETB receptor
blocker inhibits high glucose-induced fibronectin
synthesis
in
HPMC.
Perit
Dial
Int
2006;26:393-401.

19. Shimosawa T. Mechanical stress and humoral
factors linked to the induction of oxidative stress.
Hypertens Res 2006;29:643-644.
20. Shirakabe K, Priori G, Yamada H, Ando H, Horita
H, Fujita T, Fujimoto I, Mizutani A, Seki G,
Mikoshiba K. IRBIT, an inositol 1,4,5trisphosphate receptor-binding protein, specifically binds to and activates pancreas-type
Na+/HCO3- cotransporter 1 (pNBC1). Proc Natl
Acad Sci USA 2006;103:9542-9547.
21. Takeda R, Nishimatsu H, Suzuki E, Satonaka H,
Nagata D, Oba S, Sata M, Takahashi M, Yamamoto Y, Terauchi Y, Kadowaki T, Kangawa K,
Kitamura T, Nagai R, Hirata Y. Ghrelin improves
renal function in mice with ischemic acute renal
failure. J Am Soc Nephrol 2006;17:113-121.
22. Tojo A, Onozato ML, Fujita T. Repeated subileus
due to angioedema during renin-angiotensin system blockade. Am J Med Sci 2006;332:36-38.
23. Urakawa I, Yamazaki Y, Shimada T, Iijima K,
Hasegawa H, Okawa K, Fujita T, Fukumoto S,
Yamashita T. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature
2006;444:770-774..
24. Yamamoto K, Sokabe T, Matsumoto T, Yoshimura K, Shibata M, Ohura N, Fukuda T, Sato T,
Sekine K, Kato S, Isshiki M, Fujita T, Kobayashi
M, Kawamura K, Masuda H, Kamiya A, Ando J.
Impaired flow-dependent control of vascular tone
and remodeling in P2X4-deficient mice. Nat Med
2006;12:133-137.
25. Yasufuku-Takano J, Takano K, Morita K, Takakura K, Teramoto A, Fujita T. Does the prevalence of gsp mutations in GH-secreting adenomas
differ geographically or racially? - Prevalence ofgsp mutations in Japanese patients revisited. Clin
Endocrinol 2006;64:91-96.
（Total 61 publications）

133

Department of Metabolic Diseases
Professor
Takashi Kadowaki, M.D.,Ph.D.

Lecturer
Yoshiyasu Kaneko, M.D., Ph.D., Kazuyuki Tobe, M.D., Ph.D.

Associate
Kazuhisa Tsukamoto, M.D., Ph.D.,
Ken Ohashi, M.D., Ph.D.,
Masumi Hara, M.D. Ph.D.,
Midori Fujishiro, M.D., Ph.D.,

Homepage

Jun-ichi Osuga, M.D., Ph.D.
Kazuo Hara, M.D., Ph.D.
Hideyuki Sakoda, M.D., PhD.
Mitsuru Ohsugi, M.D., PhD.

http://dm.umin.jp/

Introduction and Organization
In 1998 the Department of Internal Medicine at the
University of Tokyo was reorganized to the morefunctional units based on clinical specialties of diseased organs. The physicians specialized in the metabolic diseases from 3 departments of Internal Medicine were unified to the Department of Metabolic
Diseases. The Department of Metabolic Diseases is
one of the major divisions in the Department of Internal Medicine at the University of Tokyo, and covers
metabolic diseases including diabetes mellitus, obesityand dyslipidemia.
Under the supervision and direction of the previous
professors Dr. Satoshi Kimura (1998-2003) and Dr.
Toshiro Fujita (2003) and the present Professor Dr.
Takashi Kadowaki (2003-present), we have provided awide-ranged clinical, teaching and research activities.
Currently, we hold 35 beds mainly on the 12th floor of
the Northern Ward of the Tokyo University Hospital,
and take care of more than 30 patients constantly. Besides the staffs listed above, our division holds faculties in branches, for example, 21st Century COE Program (associate professor, Dr. Kohjiro Ueki), Department of Integrated Molecular Science on Metabolic
Diseases (associate professor, Dr. Toshimasa Yamauchi), and Department of Clinical Bioinformatics. With

all these staffs, we intensively instruct and teach theresidents and under-graduate students; annual evaluation of the teaching skill by the students always rates
our department within the three places of the top. In
addition, there are around 20 students of Graduate
School in our division. With all these members, wevigorously work on the research activities, which leadto the outstanding contributions in the field of metabolism.

Clinical activities
Based on the update clinical evidences and with theexperienced skills, we provide superior andwarm-hearted medicine to each patient. We have outpatient clinics from Monday through Friday, and takecare of more than 4000 patients. In the inpatient careunit, we not only take care of more than 30 patients inour division as mentioned above, but also provide a
sophisticated management to all patients sufferingfrom metabolic diseases, especially diabetes mellitus.
Diabetes mellitus, metabolic syndrome, hyperlipidemia and obesity are very popular in Japan, and cause
complications including nephropathy, retinopathy,
neuropathy and cardiovascular diseases. Thus, in collaboration with other departments, we optimize thetreatment of each patient.

134

We provide the educational lectures to the patients
every day in the inpatient ward, and also give lectures
twice a week in the outpatient unit. In addition, in
collaboration with co-medical staffs of our hospital,
we provide patients well-reasoned instructions regarding diet therapy, excise therapy and medication
therapy.
The weekly official activities of our department are
the pre-round case conference and the Ward Round by
the Professor on Monday. We also hold a case conference by the consultation group staffs on Tuesday.

Teaching activities
As for under-graduate education, our department
takes a part in systemic lectures for the 4th year medical students, bed-side learning and clinical clerkshipfor the 5th year medical students, and clinical lectures
for the 6th year medical students.
In systemic lectures, comprehensive presentation
for the understanding of basic knowledge about theconcept, pathogenesis, diagnosis and treatment ofcommon metabolic diseases is performed.
In clinical lectures, we present clinical cases ofimportant diseases such as diabetes mellitus, and try to
discuss with the students several points for planningthe diagnosis and treatment in collaboration with thefaculties of the Departments of Nephrology, Cardiology, and Ophthalmology.
During the period of bed-side learning, the students
have opportunities to experience the daily clinical carewith junior and senior residents as well as with theFaculty members. Each student can learn how to makea medical interview, check physical findings and makethe actual plans for the diagnosis and treatment. Several lectures that lead to profound understandings ofthe metabolic diseases are provided by the staffs.
In clinical clerkship, we arrange the program so thatthe students can experience the clinical practice andlearn the disease itself more profoundly. One faculty
and one senior-resident always instruct one student.
As for the post-graduate education, attending doctor(staff) and senior resident instruct the junior residents.
We provide advanced teaching through the seminars
and grand conference.

Research activities
There are several laboratories in our departments;
collaborating with each others or with other departments, we focus on the molecular mechanisms of themetabolic diseases and the establishment of the newtreatment.
1) Molecular mechanisms of type 2 diabetes
We have been trying to elucidate the mechanisms
underlying the development of type 2 diabetes at
the molecular and genetic levels. To this end, weare exploring the signal transduction pathways ofinsulin in various tissues and the secretory mechanism of insulin under the normal or pathologicalconditions, such as diabetes and obesity, using a
number of transgenic and knockout animal models.
In particular, we are interested in the physiologicaland pathopysiological functions of some adipokines secreted by adipocytes, including adiponectinand MCP-1, and the signal transduction pathwayof adiponectin through the receptors, AdipoR1 andAdipoR2, that we identified. In addition, we havebeen successfully unraveling the molecularmechanisms of ß cell proliferation. We believethat these will provide novel therapeutic strategies
for diabetes and the metabolic syndrome.
2) Analysis of a glucose transport mechanism in insulin resistance
We analyze insulin-stimulated and contractioninduced glucose transport with technique of molecular biology. In addition, we try condition of apatient elucidation of diabetes and establishmentof a new treatment by analyzing a diabetes model
animal and mechanism of insulin resistance in a
cultured cell.
3) Pathophysiological roles of lipid storage andatherosclerosis
Our aim is to clarify the significance of metabolicrisk factors in the onset and development of atherosclerosis. We are currently investigating the pathophysiological roles of lipid storage in obesity,
fatty liver, diabetes, hyperlipidemia and atherosclerosis using strategies of molecular biology andgenetic engineering techniques.

1354) Lipid disorders and atherosclerosis
Utilizing the animal models of lipid disorders andmolecular biological technique, we are analyzing
the roles of lipid transporters, nuclear receptors
and the anti-oxidative proteins on the lipid disorders and atherosclerosis. We are currently interested in the cholesterol and lipid absorption fromthe intestine and lipid handling in the cells.

References
1. Asano T, Sakosda H, Fujishiro M, Anai M,
Kushiyama A, Horike N, Kamata H, Ogihara T,
Kurihara H, UchijimaY. Physiological significance of resistin and resistin-like molecules in the
inflammatory process and insulin resistance. Current Diabetes Reviews 2: 449-454, 2006
2. Baumgartl J, Baudler S, Scherner M, Babaev V,
Makowski L, Suttles J, McDuffie M, Tobe K,
Kadowaki T, Fazio S, Kahn CR, Hotamisligil GS,
Krone W, Linton M, Bruning JC. Myeloid lineage
cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis.
Cell Metab 3:247-256, 2006
3. Ebinuma H, Miyazaki O, Yago H, Hara K,
Yamauchi T, Kadowaki T. A novel ELISA system
for selective measurement of human adiponectin
multimers by using proteases. Clin Chim Acta
372:47-53, 2006
4. Hara K, Horikoshi M, Kitazato H, Ito C, Noda M,
Ohashi J, Froguel P, Tokunaga K, Tobe K, Nagai
R, Kadowaki T. Hepatocyte nuclear factor-4alphaP2 promoter haplotypes are associated with type 2
diabetes in the Japanese population. Diabetes
55:1260-1264, 2006
5. Hara K, Horikoshi M, Yamauchi T, Yago H, Miyazaki O, Ebinuma H, Imai Y, Nagai R, Kadowaki
T. Measurement of the high-molecular weight
form of adiponectin in plasma is useful for theprediction of insulin resistance and metabolic
syndrome. Diabetes Care 29:1357-1362, 2006
6. Hara K, Matsushita Y, Horikoshi M, Yoshiike N,
Yokoyama T, Tanaka H, Kadowaki T. A proposal
for the cutoff point of waist circumference for the
diagnosis of metabolic syndrome in the Japanese
population. Diabetes Care 29:1123-1124, 2006
7. Hara M, Iso-O N, Satoh H, Noto H, Togo M,

Ishibashi S, Kimura S, Kadowaki T, Hashimoto Y,
Tsukamoto K. Differential effects of apolipoprotein E isoforms on lipolysis of very low-density
lipoprotein triglycerides. Metabolism 55:11291134, 2006
8. Hashimoto H, Arai T, Takeguchi A, Hioki K, Ohnishi Y, Kawai K, Ito M, Suzuki R, Yamauchi T,
Ohsugi M, Saito M, Ueyama Y, Tobe K, Kadowaki T, Tamaoki N, Kosaka K. Ontogenetic characteristics of enzyme activities and plasma metabolites in C57BL/6J:Jcl mice deficient in insulin receptor substrate 2. Comp Med 56:176-187, 2006
9. He Z, Opland DM, Way KJ, Ueki K, Bodyak N,
Kang PM, Izumo S, Kulkarni RN, Wang B, Liao
R, Kahn CR, King GL. Regulation of vascularendothelial growth factor expression and vascularization in the myocardium by insulin receptor
and PI3K/Akt pathways in insulin resistance andischemia. Arterioscler Thromb Vasc Biol
26:787-793, 2006
10. Horikoshi M, Hara K, Ohashi J, Miyake K,
Tokunaga K, Ito C, Kasuga M, Nagai R,
Kadowaki T. A polymorphism in the
AMPKalpha2 subunit gene is associated withinsulin resistance and type 2 diabetes in theJapanese population. Diabetes 55:919-923, 2006
11. Iso-O N, Noto H, Hara M, Togo M, Karasawa K,
Ohashi N, Noiri E, Hashimoto Y, Kadowaki T,
Kimura S, Watanabe T, Tsukamoto K. Adenovirus-mediated gene transfer and lipoprotein-mediated protein delivery of plasma PAF-AH
ameliorates proteinuria in rat model of glomerulosclerosis. Mol Ther 13:118-126, 2006
12. Kadowaki T, Yamauchi T, Kubota N, Hara K,
Ueki K, Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and themetabolic syndrome. J Clin Invest 116:1784-1792,
2006
13. Kamei N, Tobe K, Suzuki R, Ohsugi M, Watanabe
T, Kubota N, Ohtsuka-Kowatari N, Kumagai K,
Sakamoto K, Kobayashi M, Yamauchi T, Ueki K,
Oishi Y, Nishimura S, Manabe I, Hashimoto H,
Ohnishi Y, Ogata H, Tokuyama K, Tsunoda M, Ide
T, Murakami K, Nagai R, Kadowaki T. Overexpression of monocyte chemoattractant protein-1 inadipose tissues causes macrophage recruitment
and insulin resistance. J Biol Chem 281:26602-

136

26614, 2006
14. Kubota N, Terauchi Y, Kubota T, Kumagai H, Itoh
S, Satoh H, Yano W, Ogata H, Tokuyama K,
Takamoto I, Mineyama T, Ishikawa M, Moroi M,
Sugi K, Yamauchi T, Ueki K, Tobe K, Noda T,
Nagai R, Kadowaki T. Pioglitazone ameliorates
insulin resistance and diabetes by both
adiponectin-dependentand-independent
pathways. J Biol Chem 281:8748-8755, 2006
15. Kubota N, Yamauchi T, Tobe K, Kadowaki T.
Adiponectin-dependentandadiponectinindependent pathways in insulin sensitizing andanti-diabetic actions of thiazolidinediones. Diabetes 55:32-38, 2006
16. Leiter L, Betteridge D, Chacra A, Chait A, Ferraninini E, Haffner S, Kadowaki T, Tuomilehto J,
Zimmet P, Newman C, Hey-Hadavi J, Walkinshaw
C. on behalf of the Audit Study Steering Committee : Audit study. Evidence of global undertreatment of dyslipidaemia in patients with type 2
diabetes mellitus. Achieving Best Practice 6:31-40,
2006
17. Michalik L, Auwerx J, Berger JP, Chatterjee VK,
Glass CK, Gonzalez FJ, Grimaldi PA, Kadowaki T,
Lazar MA, O'Rahilly S, Palmer CN, Plutzky J,
Reddy JK, Spiegelman BM, Staels B, Wahli W.
International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol Rev 58:726-741, 2006
18. Muranaka K, Yanagi Y, Tamaki Y, Usui T, Kubota
N, Iriyama A, Terauchi Y, Kadowaki T, Araie M.
Effects of peroxisome proliferator-activated receptor gamma and its ligand on blood-retinal barrier in a streptozotocin-induced diabetic model.
Invest Ophthalmol Vis Sci 47:4547-4552, 2006
19. Naruse K, Rask-Madsen C, Takahara N, Ha SW,
Suzuma K, Way KJ, Jacobs JR, Clermont AC,
Ueki K, Ohshiro Y, Zhang J, Goldfine AB, King
GL. Activation of vascular protein kinase C-beta
inhibits Akt-dependent endothelial nitric oxide
synthase function in obesity-associated insulin resistance. Diabetes 55:691-698, 2006
20. Nomura S, Nakajima A, Ishimine S, Matsuhashi N,
Kadowaki T, Kaminishi M. Differential expression of peroxisome proliferator-activated receptor
in histologically different human gastric cancer
tissues. J Exp Clin Cancer Res 25:443-448, 2006

21. Okazaki H, Igarashi M, Nishi M, Tajima M, Sekiya M, Okazaki S, Yahagi N, Ohashi K, Tsukamoto K, Amemiya-Kudo M, Matsuzaka T, Shimano H, Yamada N, Aoki J, Morikawa R, Takanezawa Y, Arai H, Nagai R, Kadowaki T, Osuga
J, Ishibashi S. Identification of a novel member ofthe carboxylesterase family that hydrolyzes triacylglycerol: a potential role in adipocyte lipolysis.
Diabetes 55:2091-2097, 2006
22. Okazaki H, Tazoe F, Okazaki S, Isoo N, Tsukamoto K, Sekiya M, Yahagi N, Iizuka Y, Ohashi K,
Kitamine T, Tozawa R, Inaba T, Yagyu H, Okazaki M, Shimano H, Shibata N, Arai H, Nagai RZ,
Kadowaki T, Osuga J, Ishibashi S. Increased cholesterol biosynthesis and hypercholesterolemia inmice overexpressing squalene synthase in the liver.
J Lipid Res 47:1950-1958, 2006
23. Sakakibara S, Yamauchi T, Oshima Y, Tsukamoto
Y, Kadowaki T. Acetic acid activates hepatic
AMPK and reduces hyperglycemia in diabetic
KK-A(y) mice. Biochem Biophys Res Commun
344:597-604, 2006
24. Sekine N, Takano K, Kimata-Hayashi N,
Kadowaki T, Fujita T. Adrenomedullin inhibits
insulin exocytosis via pertussis toxin-sensitive Gprotein-coupled mechanism. Am J Physiol Endocrinol Metab 291:E9-E14, 2006
25. Shinoda Y, Yamaguchi M, Ogata N, Akune T,
Kubota N, Yamauchi T, Terauchi Y, Kadowaki T,
Takeuchi Y, Fukumoto S, Ikeda T, Hoshi K,
Chung UI, Nakamura K, Kawaguchi H. Regulation of bone formation by adiponectin throughautocrine/paracrine and endocrine pathways. J
Cell Biochem 99:196-208, 2006
26. Takeda R, Nishimatsu H, Suzuki E, Satonaka H,
Nagata D, Oba S, Sata M, Takahashi M, Yamamoto Y, Terauchi Y, Kadowaki T, Kangawa K,
Kitamura T, Nagai R, Hirata Y. Ghrelin improves
renal function in mice with ischemic acute renal
failure. J Am Soc Nephrol 17:113-121, 2006
27. Takemura Y, Osuga Y, Yamauchi T, Kobayashi M,
Harada M, Hirata T, Morimoto C, Hirota Y, Yoshino O, Koga K, Yano T, Kadowaki T, Taketani Y.
Expression of adiponectin receptors and its possible implication in the human endometrium. Endocrinology 147:3203-3210, 2006
28. Taniguchi CM, Tran TT, Kondo T, Luo J, Ueki K,

137

Cantley LC, Kahn CR. Phosphoinositide 3-kinase
regulatory subunit p85alpha suppresses insulin
action via positive regulation of PTEN. Proc Natl
Acad Sci U S A 103:12093-12097, 2006
29. Ueki K, Okada T, Hu J, Liew CW, Assmann A,
Dahlgren GM, Peters JL, Shackman JG, Zhang M,
Artner I, Satin LS, Stein R, Holzenberger M,
Kennedy RT, Kahn CR, Kulkarni RN. Total insulin and IGF-I resistance in pancreatic beta cells
causes overt diabetes. Nat Genet 38:583-588,
2006
30. Viana AY, Sakoda H, Anai M, Fujishiro M, Ono
H, Kushiyama A, Fukushima Y, Sato Y, Oshida Y,
Uchijima Y, Kurihara H, Asano T. Role of hepatic
AMPK activation in glucose metabolism anddexamethasone-induced regulation of AMPK expression. Diabetes Res Clin Pract. 73:135-142,
2006
31. Wada K, Nakajima A, Katayama K, Kudo C, Shibuya A, Kubota N, Terauchi Y, Tachibana M, Miyoshi H, Kamisaki Y, Mayumi T, Kadowaki T,
Blumberg RS. Peroxisome proliferator-activatedreceptor gamma-mediated regulation of neuralstem cell proliferation and differentiation. J Biol
Chem 281:12673-12681, 2006
32. Yazaki Y, Kadowaki T. Combating diabetes andobesity in Japan. Nat Med 12:73-74, 2006
33. Yokoi N, Kanamori M, Horikawa Y, Takeda J,
Sanke T, Furuta H, Nanjo K, Mori H, Kasuga M,
Hara K, Kadowaki T, Tanizawa Y, Oka Y, Iwami Y,
Ohgawara H, Yamada Y, Seino Y, Yano H, Cox NJ,
Seino S. Association studies of variants in thegenes involved in pancreatic beta-cell function in
type 2 diabetes in Japanese subjects. Diabetes
55:2379-2386, 2006

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Department of
Hematology and Oncology
Professor
Mineo Kurokawa, M.D., Ph.D.

Lecturer
Toru Motokura, M.D.,

Yoshinobu Kanda, M.D., Ph.D.

Special Lecturer (Hospital)
Akira Hangaishi, M.D., Ph.D.

Associate
Koji Izutsu, M.D., Ph.D.,

Takashi Asai, M.D., Ph.D.,

Takuro Watanabe, M.D.,

Hiroyuki Sato, M.D., Ph.D.

Tsuyoshi Takahashi, M.D., Ph.D.

Homepage

http://www.h.u-tokyo.ac.jp/hematology/

Introduction and Organization
Department of Hematology and Oncology is responsible for clinical activities in out-patient as wellas in-patient clinics of hematological disorders, conducting research activities for hematology and oncology, and are also in charge of teaching activities forundergraduate medical students and graduate students.
These activities are performed by the united efforts ofall members who belong to the department. As of
March in 2007, the staff of Department of Hematology
and Oncology consists of thirty-nine members including one professor, 2 lecturers, one special lecturer(hospital), and 4 associates.

Clinical activities
On average, 60 patients with hematological diseases
are treated in the ward. Clinical facilities include patient rooms with high-efficiency particulate air filtration and filtrated water supply. Patients who are eligible for the treatment with high-grade infection prophylaxis are admitted to the facilities. Patient care isprovided by team management and three doctors

composed of each one of junior residents, senior residents, and associates are assigned to one patient. Since
clinical issues especially for patients with hematological tumors are highly related to the hamatopoietic
stem cell transplantation, all clinical conferences areshared with staff members of the three departments. A
number of clinical problems involved in the patientmanagement are discussed in the morning clinicalconference held every other day. Diagnostic and therapeutic issues as well as pathological aspects are also
discussed weekly in the clinical conferences, eachfocusing on hematological diseases, lymphomas, or
hematopoietic stem cell transplantation. All these
conferences are also attended by the staff member ofDepartment of Cell Therapy and Transplantation because of clinical significance of hamatopoietic stem
cell transplantation in the treatment of hematologicaldisorders.
Approximately 90 patients with acute leukemia,
120 with malignant lymphoma, 15 with chronic leukemia, 20 with multiple myeloma, 10 with myelodysplastic syndrome, and 55 with the other diseases areannually admitted to our ward. Out-patient clinicalservices are provided daily in the morning and after-

139

noon using three booths. One of our final goals in theclinical activities is to cure all patients with hematological malignancies.
Here are some technical aspects on the treatment
strategy:
1. High-dose chemotherapy with or without autologous stem cell support: High-dose chemotherapy
is administered according to the malignant disease.
For the autologous stem cell support, peripheral
blood stem cell is usually selected as a source ofstem cells. Similar procedures used in the allogeneic stem cell harvest are performed for leukapheresis and preservation.
2. Allogeneic hematopoietic stem cell transplantation: Bone marrow cells are operatively harvested
and infused without preservation. For peripheral
blood stem cell transplantation, leukapheresis isperformed with the use of an automated continuous flow blood cell separator, and harvested cells
are preserved in cooperation with Department ofTransfusion Medicine. Recently, transplantation
after pre-conditioning of reduced intensity (RIST
for reduced-intensity stem cell transplantation) is
commonly performed for the elderly patients andpatients with organ damages. The development of
this strategy is expanding the eligibility of transplant recipients. Several clinical studies with allogeneic stem cell transplantation have been also
conducted. These include RIST for pancreaticcancer, transplantation from a donor with mismatched HLA at two loci or more. All these studies are approved by the ethical committee of theFaculty of Medicine.

Teaching activities
A lecture course on etiology, pathogenesis, clinicaland laboratory features, differential diagnosis, therapy
and prognosis for all hematological diseases is provided for the second grade medical students. The
course contents include:
1. Mechanisms of hematopoiesis, transplantation
medicine and cell therapy
2. Acute leukemia and myeloproliferative disorders
3. Bone marrow failure syndrome (aplastic anemia
and myelodysplastic syndrome)
4. Lymphoma and myeloma

5. Hemostasis and thrombosis
6. Hemolytic anemia and anemia of various causes.
Courses for bedside learning on diagnostic and therapeutic issues and arts are given for the third grade
medical students on a man-to-man basis with a seniorfaculty member that are erudite both in general internal medicine and in hematology and oncology. During
the one-week case-oriented course, students learn thebasic techniques of medical interview and physicalexamination, interpretation of laboratory tests, andpractical medical procedures.

Research activities
The major research projects are focused on molecular mechanisms of hematopoietic tumors, hematopoietic transcription factors, signal transduction mechanisms in hematopoietic cells, chromosomal andgenomic approaches to leukemogenesis, generation ofmurine models for leukemias, proliferation and differentiation of hematopoietic stem cells, and development of immunotherapy for hematopoietic tumors.
Every effort has been made to achieve the highest
quality in both clinical and basic medical research.
The ultimate aims of our research are the applicationof epoch-making discoveries in research fields to theclinical hematology and oncology. Representative
publications from our departments published in thepast two years are listed in the reference.

References
1. Takahashi T, Dejbakhsh-Jones S, Strober S. Expression of CD161 (NKR-P1A) defines subsets ofhuman CD4 and CD8 T cells with different functional activities. J Immunol. 2006 Jan 1;176(1):211-6.
2. Nakagawa K, Kanda Y, Yamashita H, Hosoi Y,
Oshima K, Ohtomo K, Ban N, Yamakawa S, Nakagawa S, Chiba S. Preservation of ovarian function by ovarian shielding when undergoing total
body irradiation for hematopoietic stem celltransplantation: a report of two successful cases.
Bone Marrow Transplant. 2006 Mar;37(6):583-7.
3. Komeno Y, Kanda Y, Hamaki T, Mitani K, Iijima
K, Ueyama J, Yoshihara S, Yuji K, Kim SW, Ando
T, Kami M, Yamamoto E, Hiruma K, Mori S, Hi-140

rai H, Sakamaki H; Japan Hematology and Oncology Clinical Study Group. A randomized controlled trial to compare once- versus twice-daily
filgrastim for mobilization of peripheral blood
stem cells from healthy donors. Biol Blood Marrow Transplant. 2006 Apr;12(4):408-13.
4. Asano-Mori Y, Kanda Y, Oshima K, Watanabe T,
Shoda E, Motokura T, Kurokawa M, Chiba S.
Pharmacokinetics of ganciclovir in haematopoietic stem cell transplantation recipients with orwithout renal impairment. J Antimicrob Chemother. 2006 May;57(5):1004-7.
5. Hosoya N, Sanada M, Nannya Y, Nakazaki K,
Wang L, Hangaishi A, Kurokawa M, Chiba S,
Ogawa S. Genomewide screening of DNA copy
number changes in chronic myelogenous leukemia with the use of high-resolution array-based
comparative genomic hybridization. Genes
Chromosomes Cancer. 2006 May;45(5):482-94.
6. Nakamura Y, Sato H, Motokura T. Developmentof multidrug resistance due to multiple factors including P-glycoprotein overexpression underK-selection after MYC and HRAS oncogene activation. Int J Cancer. 2006 May 15;118(10):244854.
7. Sato H, Nakamura Y, Motokura T. Differential
14-3-3 sigma DNA methylation and expression inc-myc- and activated H-ras-transformed cells under r- and K-selection. Cancer Lett. 2006 May
8;236(1):105-14.
8. Seo S, Ichikawa M, Kurokawa M. Structure andfunction of cas-L and integrin-mediated signaling.
Crit Rev Immunol. 2006;26(5):391-406.
9. Kusama M, Kubota T, Matsukura Y, Matsuno K,
Ogawa S, Kanda Y, Iga T. Influence of glutathione
S-transferase A1 polymorphism on the pharmacokinetics of busulfan. Clin Chim Acta. 2006 Jun;
368(1-2):93-8.
10. Masuda S. The molecular mechanism of
Notch-induced transformation and the therapeuticpotential of its inhibitor Rinsho Ketsueki. 2006
Jul;47(7):557-63.
11. Kurokawa M. AML1/Runx1 as a versatile regulator of hematopoiesis: regulation of its function
and a role in adult hematopoiesis. Int J Hematol.
2006 Aug;84(2):136-42.
12. Yamashita H, Izutsu K, Nakamura N, Shiraishi K,

Chiba S, Kurokawa M, Tago M, Igaki H, Ohtomo
K, Nakagawa K. Treatment results of chemoradiation therapy for localized aggressive lymphomas:
A retrospective 20-year study. Ann Hematol. 2006
Aug;85(8):523-9.
13. Haraguchi K, Takahashi T, Nakahara F, Matsumoto A, Kurokawa M, Ogawa S, Oda H, Hirai H,
Chiba S. CD1d expression level in tumor cells is
an important determinant for anti-tumor immunity
by natural killer T cells. Leuk Lymphoma. 2006
Oct;47(10):2218-23.
14. Nakagawa M, Ichikawa M, Kumano K, Goyama S,
Kawazu M, Asai T, Ogawa S, Kurokawa M, Chiba
S. AML1/Runx1 rescues Notch1-null mutationinduced deficiency of para-aortic splanchnopleural hematopoiesis. Blood. 2006 Nov 15;108(10):3329-34.
15. Oshima K, Kanda Y, Nakahara F, Shoda E, Suzuki
T, Imai Y, Watanabe T, Asai T, Izutsu K, Ogawa S,
Motokura T, Chiba S, Kurokawa M. Pharmacokinetics of alemtuzumab after haploidentical HLAmismatched hematopoietic stem cell transplantation using in vivo alemtuzumab with or without
CD52-positive malignancies. Am J Hematol. 2006
Nov;81(11):875-9.
16. Suzuki T, Yokoyama Y, Kumano K, Takanashi M,
Kozuma S, Takato T, Nakahata T, Nishikawa M,
Sakano S, Kurokawa M, Ogawa S, Chiba S.
Highly efficient ex vivo expansion of human hematopoietic stem cells using Delta1-Fc chimeric
protein. Stem Cells. 2006 Nov;24(11):2456-65.
17. Chiba S. Notch signaling in stem cell systems.
Stem Cells. 2006 Nov;24(11):2437-47.
18. Kanda Y, Hyo R, Yamashita T, Fujimaki K,
Oshima K, Onoda M, Mori T, Sakura T, Tanaka M,
Sakai M, Taguchi J, Kurokawa M, Maruta A,
Okamoto S, Sakamaki H; Kanto Study Group of
Cell Therapy. Effect of blood cyclosporine concentration on the outcome of hematopoietic stem
cell transplantation from an HLA-matched sibling
donor. Am J Hematol. 2006 Nov;81(11):838-44.
19. Nishiyama U, Yoshino T, Ozai M, Yoshioka R,
Fujisawa M, Ogasawara Y, Kitahori M, Yoshioka
E, Kubo K, Komeno Y, Kurokawa M, Ogawa S,
Chiba S, Osawa T, Kuwaki T, Hirai H, Miwa A.
Antineoplastic effect of a single oral dose of thenovel Flt3 inhibitor KRN383 on xenografted hu-

141

man leukemic cells harboring Flt3-activating mutations. Leuk Res. 2006 Dec;30(12):1541-6.

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Department of Allergy andRheumatology
Professor
Kazuhiko Yamamoto, M.D. ( Rheumatology, Allergology )Lecturer
Fujio Takeuchi, M.D. (Rheumatology)

Yoshikata Misaki, M.D. (Rheumatology)

Makoto Dohi, M.D. (Allergology )Zen-ichiro Honda, M.D. (Rheumatology)

Assistant
Tetsuji Sawada, M.D. (Rheumatology)

Masao Yamaguchi, M.D. (Allergology )Ryoichi Tanaka, M.D. (Allergology )Hiroko Kanda, M.D. (Rheumatology)

Kimito Kawahata, M.D. (Rheumatology)

Keishi Fujio, M.D. (Rheumatology)

Homepage
The Department of Allergy and Rheumatology presently consists of 10 staff mentioned above, who preside over 6 medical staff, 15 graduate students for"Doctor of Medical Science" and 3 staff studying
abroad. The outpatient facilities are situated on the
2nd floor of the Outpatient Clinic. The inpatient facility is mainly located on the 13th floor of the Hospital
Ward A. The physician's office is situated in the East
Hospital Ward and the research rooms are located in
the East Hospital Ward, the Central Ward and the Internal Medicine Research Ward.

Education
In regard to undergraduate education, the Department is in charge of internal medicine diagnosis andsystemic lectures for M2 students and clinical lecturesand bedside education for M3 and M4 students in cooperation with other departments of internal medicine.
The systemic lectures and clinical lectures covers
clinical immunology, connective tissue diseases andallergy. Bedside education provides students with agood opportunity to learn about patients as well aspractical knowledge through numerous seminars.

For postgraduate education, internal medicine trainees are accepted on rotation basis and trained as internist. Our department accepts students for "Doctorof Medical Science". Our 4-year education covers
clinical immunology, molecular immunology, rheumatology and allergology.

Medical Care
General and special outpatient clinics are opened
from Monday to Friday. Special outpatients clinics
include clinics for rheumatoid arthritis, connective
tissue diseases, bronchial asthma, allergy, and kidney
disorders. For inpatients, there are presently 25 to 30
beds. Every week on Monday afternoon the charts arerounded and on Tuesday afternoon the professor
makes his rounds. To achieve the highest quality of
medical care, clinical conferences are held. Majorityof patients in the ward are suffered from connective
tissue diseases and usually exhibit multiple organ involvements. Therefore, a careful, well-rounded approach to each patient as a whole is required rather
than a limited special approach to a single organ system.

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Research
The Department has 10 research laboratories inwhich clinical and basic studies are carried out concerning mainly rheumatology and allergology. Recently the mainstream of research has employed various techniques of molecular biology and cellular immunology. The principal research topics are listed below.
1) Analysis by means of autoantigen gene cloning
and epitope mapping.
2) Analysis of the mechanisms of tolerance breakdown to systemic autoantigens using transgenicmice.
3) Analysis of antigen specific T cell clonalities in
immunological disorders.
4) Genetic analysis of rheumatoid arthritis and otherconnective tissue diseases.
5) Development of new gene therapies for immunological diseases.
6) Analysis of the mechanisms of oral tolerance.
7) Analysis of signal transduction mechanisms in
immunological disorders.
8) Development and analysis of animal models of
bronchial asthma.
9) Study of signal transduction of IgE mediated mastcell activation.
10) Regulation of IgE antibody production.
11) Analysis of cytokines and chemokines in the pathogenesis of allergic conditions.
12) Analysis of interstitial pneumonitis associatedwith connective tissue diseases,13) Mechanism of drug allergy

References
2006-2007(1) Nagatani K, Dohi M, To Y, Tanaka R, Okunishi
K, Nakagome K, Sagawa K, Tanno Y, Komagata
Y, Yamamoto K. Splenic dendritic cells induced
by oral antigen administration are important for
the transfer of oral tolerance in an experimental
model of asthma. J Immunol. 176:1481-9, 2006.
(2) Okazaki Y, Suzuki A, Sawada T, OhtakeYamanaka M, Inoue T, Hasebe T, Yamada R,
Yamamoto K. Identification of citrullinated eukaryotic translation initiation factor 4G1 as novelautoantigen in rheumatoid arthritis. Biochem Biophys Res Commun. 341:94-100, 2006.
(3) Komiya A, Nagase H, Okugawa S, Ota Y, Suzukawa M, Kawakami A, Sekiya T, Matsushima K,
Ohta K, Hirai K, Yamamoto K, Yamaguchi M.
Expression and function of toll-like receptors inhuman basophils. Int Arch Allergy Immunol.
140:23-27, 2006.
(4) Suzukawa M, Yamaguchi M, Komiya A, Kimura
M, Nito T, Yamamoto K. Ortho-phthalaldehydeinduced anaphylaxis following laryngoscopy. J
Allergy Clin Immunol. 117:1500-1501, 2006.
(5) Suzukawa M, Komiya A, Iikura M, Nagase H,
Yoshimura-Uchiyama C, Yamada H, Kawasaki H,
Ohta K, Matsushima K, Hirai K, Yamamoto K,
Yamaguchi M. Trans-basement membrane migration of human basophils: Role of matrix metalloproteinase-9. Int Immunol. 18: 1575-1583, 2006.
(6) Takizawa Y, Suzuki Akari、Sawada Tetsuji, Ohsaka Miyako, Inoue Tetsufumi, Yamada Ryo,Yamamoto Kazuhiko. Citrullinated fibrinogendetected as a soluble citrullinated autoantigen inrheumatoid arthritis synovial fluids. Ann Rheum
Dis. 65:1013-20, 2006.
(7) Shoda H, Fujio Ki, Yamaguchi Y, Okamoto A,
Sawada T, Kochi Y, Yamamoto K. Interactions
between interleukin-32 and TNF-a contribute to
the exacerbation of immune-inflammatory diseases. Arthritis Res Ther. 8:R166, 2006.
(8) Nagatani K, Dohi M, To Y, Tanaka R, Okunishi K,
Nakagome K, Sagawa K, Tanno Y, Komagata Y,
Yamamoto K. Splenic dendritic cells induced byoral antigen administration are important for thetransfer of oral tolerance in an experimental
model of asthma. J Immunol. 176:1481-1489,
2006.
(9) Shoda H, Nakazaki K, Izutsu K, Tanaka R, Komagata Y, Misaki Y, Yamamoto K. : Epstein-Barrvirus-associated mononucleosis caused by weekly
low-dose methotrexate therapy in a rheumatoid
arthritis patient.Scand J Rheumatol. 35:152-153,
2006.
(10) Nakagome K, Dohi M, Okunishi K, Tanaka R,
Miyazaki J, Yamamoto K. In vivo IL-10 gene delivery attenuates bleomycin induced pulmonary
fibrosis by inhibiting the production and activation of TGF-beta in the lung. Thorax. 61:886-894,

144

2006.
(11) Nakaya M, Dohi M, Okunishi K, Nakgome K,
Tanaka R, Imamura M, Baba S, Takeuchi N, Yamamoto K, Kaga K. Noninvasive system forevaluating allergen-induced nasal hypersensitivity in murine allergic rhinitis. Lab Invest.
86:917-926, 2006.
(12) Fujio K, Okamoto A, Araki Y, Shoda H, Tahara H,
Tsuno NH, Takahashi K, Kitamura T, Yamamoto
K.Gene therapy of arthritis with TCR isolated
from the inflamed paw. J Immunol. 177:81408147, 2006.
(13) Suzukawa M, Komiya A, Yoshimura-Uchiyama C,
Kawakami A, Koketsu R, Nagase H, Iikura M,
Yamada H, Ra C, Ohta K, Yamamoto K, Yamaguchi M. IgE-and FceRI-mediated enhancementof surface CD69 expression in basophils: Role of
low-level stimulation. Int Arch Allergy Immunol.
143:56-59, 2007.
(14) Suzukawa M, Komiya A, Koketsu R, Kawakami
A, Kimura M, Nito T, Yamamoto K, Yamaguchi
M. Three cases of Ortho-phthalaldehyde-induced
anaphylaxis after laryngoscopy: detection of specific IgE in serum. Allergology International.
56:313-316, 2007.
(15) Nakaya M, Dohi M, Okunishi K, Nakgome K,
Tanaka R, Immamura M, Yamamoto K, Kaga K.
Prolonged allergen challenge in murine nasal allergic rhinitis: nasal airway remodeling and adaptation of nasal airway responsiveness. Laryngoscope. 117:881-885, 2007.
(16) Nakagome K, Dohi M, Okunishi K, Tanaka R,
Kouro T, Kano MR, Miyazono K, Miyazaki J,
Takatsu K, Yamamoto K. IL-5-inudced hypereosinophilia suppresses the antigen-induced
immune response via a TGF-beta-dependent mechanism. J Immunol. 179:284-294, 2007.
(17) Yamamoto K, Okamoto A, Fujio K.Antigenspecific immunotherapy for autoimmune diseases.
Expert Opin Biol Ther. 7:359-367, 2007.
(18) Shoda H, Fujio K, Yamamoto K. Rheumatoid
Arthritis and Interleukin-32. Cell Mol Life Sci.
2007 Jul 9 [Epub ahead of print](19) Fujio K, Okamura T, Okamoto A, Yamamoto K. T
cell receptor gene therapy for autoimmune diseases. ANN NY Acad Sci. 2007 in press.
(20) Fujio K, Okamura T, Okamoto A, Yamamoto K. T

cell receptor and anti-inflammatory gene modulated T cells as therapy for autoimmune diseases.
Expert Rev Clin Immunol. 2007 in press.
(21) Yamaguchi Y, Fujio K, Shoda H, Okamoto A,
Tsuno NH, Takahashi K, Yamamoto K. Interleukin-17B and interleukin-17C are associatedwith TNF-alpha production and contribute to theexacerbation of inflammatory arthritis. J Immunol.
2007 in press.
(22) Okunishi K, Dohi M, Fujio K, Nakagome K, Tabata Y, Okasora T, Seki M, Shibuya M, Imamura
M, Harada H, Tanaka R, Yamamoto K. Hepatocyte growth factor significantly suppresses collagen-induced arthritis in mice. J Immunol. 2007 inpress.
(23) Kawahata K, Yamaguchi M, Kanda H, Komiya A,
Tanaka R, Dohi M, Misaki Y, Yamamoto K. Severe airflow limitation in two patients with systemic lupus erythematosus: effect of inhalation of
anticholinergics. Modern Rheumatology. in press,
2007.

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Department of Infectious
Diseases (Internal Medicine)
Professor
Kazuhiko Koike, M.D., Ph.D.

Associate Professor(To be appointed)

Associate
Yasuo Ota, M.D., Ph.D.

Homepage

http://infect.umin.jp/

Introduction and Organization
The Department of Infectious Diseases has been
one of the leading academic organizations specialized
for internal medicine, in particular, infectious disease
medicine in Japan since 1998, when the Departmentsof Internal Medicine, established in 1890, were rearranged into new ones according to subspecialty ofinternal medicine. Our department has been chiefly
engaged in clinical, educational and research activities
for infectious diseases including bacterial, fungal andviral infections of all organs including HIV infection,
tuberculosis and viral hepatitis. Our department islocated on 11th floor of the University of Tokyo Hospital Building, and has well-furnished research laboratories including P-2 class laboratory, a departmental
library and a computer room as own properties. In
clinical and research activities, we are collaboratingwith the Department of Infection Control and Prevention. A professor, an associate professor, 6 guest lecturers, an associate, 9 graduate students and 15
full-time staff member are all performing their own
duties in clinical, educational and research activities.

Clinical activities
We have hospital beds on the 11th floor of the Ward
A of University of Tokyo Hospital. Diseases include

HIV infection, viral hepatitis, pneumonia, resistantbacteria infections such as MRSA, BLNAR or VRE,
tuberculosis, EBV infection, CMV infection, parasite
infection, etc. Every effort is made to give patients thebest care and best quality of life. Clinical associates,
full-time staff and residents take care of inpatients.
The case presentation by residents is held on a weekly
basis. Weekly clinical conference is held for discussing about all cases, in particular, those with problems
difficult to be solved. Consultations are very frequentfrom other departments on the management of infectious diseases. The general diagnostic, therapeuticplans and decisions for each patient are given at theProfessor’s round.
Our department offers out-patient care everyday on
infectious diseases and general medicine. We are also
engaged in infection control and prevention of
emerging infectious diseases such SARS or avian influenza virus, which appeared recently.

Teaching activities
Our department takes a part in clinical lectures andbed-side teaching of the internal medicine for undergraduate medical students according to the educational programs of the University of Tokyo. For the
fourth year medical students, six lectures of infectious
diseases are given. In addition, principles of medical

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diagnosis are taught at the bedside. During the
bed-side teaching for fifth and sixth year students, ourassociates teach them on man-to man basis the basic
way of thinking for correct diagnosis and therapy, thetechniques of interrogation and physical examination,
the way for interpretations of laboratory tests and other medical examinations, and the basic medical procedures on each case. The education of junior residents is performed as described in “Clinical Activities”.

Research activities
Both clinical and basic researches are necessary to
improve the diagnosis and treatment. The members ofour department are doing best to obtain new findings
using highly sophisticated methodologies. A monthly
intramural research conference is held, in which twoto three members present their annual research progresses to be discussed by all the department staff. In
addition, each laboratory holds its own conference
and/or journal club on a weekly or bi-weekly basis.
The research field covers wide areas of infectious
diseases including HIV infection, viral hepatitis andhepatocarcinogenesis, CMV infection and tuberculosis(Mycobacterium infection). Also, various emerging
and re-emerging infectious diseases are covered. Following themes are currently being investigated in thedepartment.
(1) Establishment of effective therapy for HIV infection: we have made a great contribution in the establishment of the guideline for treatment of HIV
infection in Japan.
(2) Elucidation of the mechanism of hepatocarcinogenesis in hepatitis viral infection: the direct involvement of both HBV and HCV in hepatocarcinogenesis has been demonstrated using ourtransgenic mouse systems.
(3) Establishment of effective therapy for HCV and
HBV infection: we have made a great contribution
in the establishment of the guideline for treatmentof hepatitis viral infection in Japan.
(4) Establishment of effective therapy for HCV/HIV
co-infection: we have made a great contribution in
the establishment of the guideline for treatment of
HCV/HIV co-infection in Japan.
(5) Establishment of the criteria for prediction andearly diagnosis of CMV infection associated with
HIV infection.
(6) Innovation of new methods to control viral hepatitis or prevent the development of hepatocellular
carcinoma in chronic viral hepatitis.
(7) Establishment of the effective infection control
method of MRSA and other MDRO infection.
(8) Elucidating the mechanism and signal transduction of bacterial infection through toll-like receptors.
(9) Analysis of intracellular function and signaling of
the proto-oncogene Cbl.
(10) Establishment of new methods for practical diagnosis and treatment of respiratory infection.

Members
Kazuhiko Koike, Yasuo Ota, Hiroshi Yotsuyanagi,
Yoshizumi Shintani, Takeya Tsutsumi, Satoshi Itoyama, Takatoshi Kitazawa, Kuniko Ueda, Shuji
Hatakeyama, Kunihisa Tsukada, Shu Okugawa, Miki
Kawada, Shintaro Yanagimoto, Yohko Nukui,
Katsutoshi Abe, Atsuhito Fukishima, Keita Tatsuno,
Sohei Harada, Koji Goto, Mahoko Kamimura, Yusuke
Yoshino, Takahiro Aoki.

References
1) Koike K. Hepatitis C virus infection presenting
with metabolic disease by inducing insulin resistance. Intervirology 2006;49:51-57.
2) Koike K, Miyoshi H. Oxidative stress and hepatitis C viral infection. Hepatol Res 2006;34:65-76.
3) Nukui Y, Tajima S, Kotaki A, Ito M, Takasaki T,
Koike K, Kurane I. Novel dengue virus type 1
from travelers to Yap State, Micronesia. Emerg
Infect Dis 2006;12: 343-346.
4) Koike K. Oxidative stress and apoptosis in hepatitis C: the core issue. J Gastroenterology 2006;41:
292-294.
5) Okuse C, Yotsuyanagi H, Nagase Y, Kobayashi Y,
Yasuda Y, Koike K, Iino S, Suzuki M, Itoh F. Risk
Factors for Retinopathy Associated with Interferon Alpha-2b and Ribavirin Combination Therapy in Patients with Chronic Hepatitis C. World J
Gastroenterol 2006;12:3759-3759.
6) Matsuoka-Aizawa S, Gatanaga H, Sato H, Koike

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K, Kimura K, Oka S. Gag substitutions responsible for nelfinavir-dependent enhancement of precursor cleavage and human immunodeficiency
virus type-1 replication. Antiviral Res 2006;70:
51-59.
7) Saito R, Sato K, Kumita W, Inami N, Nishiyama
H, Okamura N, Moriya K, Koike K. Role of type
II topoisomerase mutations and AcrAB efflux
pump in fluoroquinolone-resistant clinical isolatesof Proteus mirabilis. J Antimicrob Chemoth 2006;
58:673-677.
8) Okugawa S, Yanagimoto S, Tsukada K, Kitazawa
T, Koike K, Kimura S, Nagase H, Hirai K, Ota Y.
Bacterial fragelin inhibits T cell receptor-mediated activation of T cells by inducing
suppressor of cytokine signaling-1 (SOCS-1). Cell
Microbiol 2006;8:1571-1580.
9) Kitazawa T, Ota Y, Kada N, Morisawa Y, Yoshida
A, Koike K, Kimura S. Successful vancomycin
desensitization with a combination of rapid andslow infusion methods. Intern Med 2006;45:317321.
10) Koike K. Antiviral treatment of hepatitis C: present status and future prospects. J Infect Chemother 2006;12:227-232.
11) Takahashi H, Yotsuyanagi H, Yasuda K, Koibuchi
T, Suzuki M, Kato T, Nakamura T, Iwamoto A,
Nishioka K, Iino S, Koike K, Itoh F. Molecularepidemiology of hepatitis A virus in metropolitan
areas in Japan. J Gastroenterol 2006;41:981-986.
12) Shin N, Sugawara Y, Tsukada K, Tamura S,
Akamatsu N, Okugawa S, Koike K, Kikuchi K,
Makuuchi M. Successful treatment of disseminated Nocardia farcinica infection in a living
donor liver transplantation recipient. Transpl
Infect Dis 2006 ;8:222-225.
13) Okuse C, Adachi K, Katakura Y, Matsunaga K,
Ishii T, Matsumoto N, Yotsuyanagi H, Iino S,
Suzuki M, Itoh F. A case of deep venous thrombosis associated with pegylated interferon alpha2b
plus ribavirin treatment of chronic hepatitis C. J
Gastroenterol. 2006;41:1231-1236.
14) Sugauchi F, Orito E, Ohno T, Tanaka Y, Ozasa A,
Kang JH, Toyoda J, Kuramitsu T, Suzuki K, Tanaka E, Akahane Y, Ichida T, Izumi N, Inoue K,
Hoshino H, Iino S, Yotsuyanagi H, Kakumu S,
Tomita E, Okanoue T, Nishiguchi S, Murawaki Y,

Hino K, Onji M, Yatsuhashi H, Sata M, Miyakawa Y, Ueda R, Mizokami M. Spatial andchronological differences in hepatitis B virus
genotypes from patients with acute hepatitis B in
Japan. Hepatol Res. 2006;36:107-114.
15) Yamada N, Okuse C, Nomoto M, Orita M, Katakura Y, Ishii T, Shinmyo T, Osada H, Maeda I,
Yotsuyanagi H, Suzuki M, Itoh F. Obstructive
jaundice caused by secondary pancreatic tumor
from malignant solitary fibrous tumor of pleura: acase report. World J Gastroenterol. 2006;12:49224926.
16) Okuse C, Yotsuyanagi H, Yamada N, Ikeda H,
Takahashi H, Suzuki M, Kondo S, Kimura K,
Koike J, Itoh F. Successful treatment of hepatitis
B virus-associated membranous nephropathy withlamivudine. Clin Nephrol. 2006;65:53-56.
17) Tanaka E, Matsumoto A, Suzuki F, Kobayashi M,
Mizokami M, Tanaka Y, Okanoue T, Minami M,
Chayama K, Imamura M, Yatsuhashi H, Nagaoka
S, Yotsuyanagi H, Kawata S, Kimura T, Maki N,
Iino S, Kiyosawa K; HBV Core-Related Antigen
Study Group. Measurement of hepatitis B virus
core-related antigen is valuable for identifying patients who are at low risk of lamivudine resistance.
Liver Int. 2006;26:90-96.
18) Ikeda H, Suzuki M, Takahashi H, Kobayashi M,
Okuse N, Moriya H, Koike J, Maeyama S,
Yotsuyanagi H, Itoh F. Hepatocellular carcinoma
with silent and cirrhotic non-alcoholic steatohepatitis, accompanying ectopic liver tissue attached togallbladder. Pathol Int. 2006;56:40-45.
19) Ogata K, Ide T, Kumashiro R, Kumada H,
Yotsuyanagi H, Okita K, Akahane Y, Kaneko S,
Tsubouchi H, Tanaka E, Moriwaki H, Nishiguchi
S, Kakumu S, Mizokami M, Iino S, Sata M. Timing of interferon therapy and sources of infection
in patients with acute hepatitis C. Hepatol Res.
2006;34:35-40.
20) Koike K, Tsukada K, Yotsuyanagi H, Moriya K,
Kikuchi Y, Oka S, Kimura S. Prevalence of Coinfection with Human Immunodeficiency Virus andHepatitis C Virus in Japan. Hepatol Res 2007;37:
2-5.
21) Bi X, Gatanaga H, Koike K, Kimura S, Oka S.
Reversal periods and patterns from drug resistant
to wild-type HIV-1 after cessation of anti-HIV

148

therapy. AIDS Res Hum Retro 2007;23:43-50.
22) Miyamoto H, Moriishi K, Moriya K, Murata S,
Tanaka K, Suzuki T, Miyamura T, Koike K, Matsuura Y. Hepatitis C Virus Core Protein Induces
Insulin Resistance through a PA28γ-Dependent
Pathway. J Virol 2007;81:1727-1735.
23) Moriishi K, Mochizuki R, Moriya K, Miyamoto H,
Mori Y, Abe T, Murata S, Tanaka K, Suzuki T,
Miyamura T, Koike K, Matsuura Y. Critical role of
PA28 γ in hepatitis C virus-associated steatogenesis and hepatocarcinogenesis. Proc Natl Acad
Sci USA 2007;104:1661-1666.
24) Ishizaka N, Saito K, Furuta K, Matsuzaki G, Koike K, Noiri E, Nagai R. Angiotensin II-induced
regulation of the expression and localization ofiron metabolism-related genes in the rat kidney.
Hypertens Res 2007;30:195-202.
25) Suzuki Y, Yotsuyanagi H, Okuse C, Nagase Y,
Takahashi H, Moriya K, Suzuki M, Koike K, Iino
S, Itoh F. Fatal liver failure caused by reactivationof lamivudine-resistant hepatitis B virus: A casereport. World J Gastroenterol 2007;13:964-969.
26) Hatakeyama S, Sugaya N, Ito M, Yamazaki M,
Ichikawa M, Kimura K, Kiso M, Shimizu H, Kawakami C, Koike K, Mitamura K, Kawaoka Y.
Emergence of Influenza B Viruses With Reduced
Sensitivity to Neuraminidase Inhibitors. JAMA
2007;297:1435-1442.
27) Saito R, Kumita W, Sato K, Chida T, Okamura N,
Moriya K, Koike K. Detection of plasmid-mediated quinolone resistance associatedwith qnrA in an Escherichia coli clinical isolate
producing CTX-M-9 beta-lactamase in Japan. Int
J Antimicrob Agents 2007;29:600-602.
28) Ishizaka N, Ishizaka Y, Toda EI, Nagai R, Koike
K, Hashimoto H, Yamakado M. Relationship between smoking, white blood cell count and metabolic syndrome in Japanese women. Diabetes Res
Clin Pract 2007 Mar 10; [Epub ahead of print]29) Kitazawa T, Nakayama K, Okugawa S, Koike K,
Shibasaki Y, Ota Y. Biphasic regulation oflevofloxacin on lipopolysaccharide-induced IL1beta production. Life Sci 2007;80:1572-1577.
30) Okugawa S, Ota Y, Tatsuno K, Tsukada K, Kishino S, Koike K. A case of invasive central
nervous system aspergillosis treated with micafungin with monitoring of micafungin concentra-

tions in the cerebrospinal fluid. Scand J Infect Dis
2007;39:344-346.
31) Takahashi H, Suzuki M, Ikeda H, Kobayashi M,
Sase S, Yotsuyanagi H, Maeyama S, Iino S, Itoh F.
Evaluation of Quantitative Portal Venous, Hepatic
Arterial, and Total Hepatic Tissue Blood Flow
Using Xenon CT in Alcoholic Liver Cirrhosis:
Comparison With Liver Cirrhosis C. Alcohol Clin
Exp Res 2007;31:S43-S48.
32) Koike K. Pathogenesis of HCV-associated HCC:
dual-pass carcinogenesis through the activation ofoxidative stress and intracellular signaling. Hepatol Res 2007 in press.
33) Yotsuyanagi H, Koike K. Mechanisms underlying
drug resistance in antiviral treatment for infections with hepatitis B and C viruses. J Gastroenterol 2007 in press.
34) Saito R, Sato K, Kumita W, Inami N, Nishiyama
H, Okamura N, Moriya K, Koike K. Detection ofplasmid-mediated quinolone resistance associatedwith qnrA in Escherichia coli clinical isolate producing CTX-M-9 beta-lactamase in Japan. Int J
Antimicrob Agents 2007 in press.
35) Aono J, Yotsuyanagi H, Miyoshi H, Tsutsumi T,
Fujie H, Shintani Y, Moriya K, Okuse C, Suzuki
M, Yasuda K, Iino S, Koike K. Amino acid substitutions in S region of hepatitis B virus in thesera from patients with acute hepatitis. Hepatol
Res 2007 in press.
36) Ichibangase T, Moriya K, Koike K, Imai K. A
novel proteomics method revealed disease-related
proteins in the liver of hepatitis C mouse model. J
Proteome Res 2007 in press.

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Department of Stress Science andPsychosomatic Medicine
Professor
Akira Akabayashi, M.D., Ph.D.

Associate Professor
Hiroaki Kumano, M.D., Ph.D.

Associate
Kazuhiro Yoshiuchi, M.D., Ph.D.,

Homepage

Yoshiyuki Takimoto, M.D., Ph.D.

http://psmut.umin.ac.jp/

Introduction and Organization
The Department of Stress Science and Psychosomatic Medicine is one of 11 divisions of the Department of Internal Medicine, the University of Tokyo. It
covers eating disorder, panic disorder, and various
psychosomatic diseases such as chronic headache,irritable bowel syndrome, functional dyspepsia, hypertension, diabetes mellitus, and hyperthyroidism.
Our teaching staff consists of one professor, one associate professor, two associates, and 5 adjunct professors, and other members are 2 senior residents, 10
graduate students, and 7 researchers.

Clinical activities
Our department is responsible for both outpatient
clinic and inpatient ward. The ward is managed as apart of the Division of General Internal Medicine, andsenior residents, an associate, and the associate professor attend it every day and provide close side-byside instruction to junior residents. The weekly professor’s round is scheduled on Thursday morning.
During 2006 April to 2007 March, 82 patients wereadmitted to the ward, many of whom were eating disorder patients. Outpatient clinic is attended on every
morning and afternoon in three consultation rooms byapproximately fifteen physicians. During 2006 April

to 2007 March, the numbers of the new outpatientsand of the overall outpatients in our department were
335 and 7262, respectively.

Teaching activities
We are giving 6 methodical lectures on psychosomatic medicine for fourth grade medical students,‘problem-based learning’ lasting 12 weeks (net 24
hours) for 6 or 7 fourth grade students, ‘bed-side
learning’ for fifth grade students lasting two weeks,‘clinical clerkship’ for 3 to 4 fifth grade students lasting 4 weeks each, and a clinical lecture on panic disorder for sixth grade students. We are trying to teachthem not only basic knowledge of specific diseases,
ways of physical examination, or interpretation of laboratory data, but also relevant ways of clinical interview, doctor-patient relationship building, and behavior modification.
As for education for junior residents, our seniorresidents and an associate provide man-to-man instruction. In addition, they can learn how to present
the history of newly-admitted patients at the weekly
professor’s round from our teaching staff.

Research activities
Targeting stress-related diseases such as not only

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those covered by our department but also other lifestyle-related disease, and cancers, we are investigating
their pathophysiology and psychopathology throughassessing bio-psycho-behavioral time-series data,various questionnaire data, and autonomic nervous
function. We are also actively conducting basic aswell as clinical research on eating-related substances.
Some representative research methods are as follows:
1) Ecological momentary assessment (EMA): Investigation on neurobehavioral basis of stress-relateddiseases such as tension-type headache, eating
disorders, insomnia, and panic disorder using
portable computers for real-time assessment ofsubjective symptoms in combination with ambulatory monitors such as electrocardiogram and actigraphy.
2) Neuroendocrinological and neuroimmunologicalstudies in anorexia nervosa patients: multidisciplinary investigation on energy metabolism duringa refeeding phase; changes in various substancessuch as neuropeptides before and after treatment;
relationship between bone metabolism and various
makers; and exploration of biomarkers for evaluating treatment efficacy.
Ten graduate students and 7 researchers actively
conducted their researches along with our teaching
staff. We have been also collaborating with many scientists belonging to other departments either in Japanor abroad. Research conferences are held once amonth, where one of the graduate students presents
his/her research for open discussion by all the members of our department.

References
1. Struzik ZR, Yoshiuchi K, Sone M, Ishikawa T,
Ki-kuchi H, Kumano H, Watsuji T, Natelson BH,
Ya-mamoto Y. “Mobile Nurse” platform for ubiquitous medicine. Method Inform Med 2007, 46:
130-134
2. Akabayashi A, Slingsby BT. Informed consent
re-visited: Japan and the U.S. Am J Bioeth. 2006,
6:9-14.
3. Kikuchi H, Yoshiuchi K, Miyasaka N, Ohashi K,
Yamamoto Y, Kumano H, Kuboki T, Akabayashi

A. Reliability of recalled self-report on headache
inten-sity: investigation using ecological momentary as-sessment technique. Cephalalgia. 2006,
26:1335-43.
4. Moriya J, Takimoto Y, Yoshiuchi K, Shimosawa T,
Akabayashi A. Plasma agouti-related protein levels in women with anorexia nervosa. Psychoneuroendo-crinology. 2006, 31: 1057-61.
5. Yoshida NM, Yoshiuchi K, Kumano H, Sasaki T,
Kuboki T. Changes in heart rate with refeeding inanorexia nervosa: a pilot study. J Psychosom Res.
2006, 61:571-5.
6. Sakai Y, Kumano H, Nishikawa M, Sakano Y,
Kaiya H, Imabayashi E, Ohnishi T, Matsuda H,
Yasuda A, Sato A, Diksic M, Kuboki T. Changes
in cerebral glucose utilization in patients withpanic disorder treated with cognitive-behavioral
therapy. Neuroi-mage. 2006, 15;33:218-26
7. Yoshiuchi K, Nakahara R, Kumano H, Kuboki T,
Togo F, Watanabe E, Yasunaga A, Park H, Shephard RJ, Aoyagi Y: Yearlong physical activity
and de-pressive symptoms in older Japanese
adults: cross-sectional data from the Nakanojo
Study. Am J Geriatr Psychiatry. 2006, 14:621-4.
8. Yoshiuchi K, Farkas J, Natelson BH. Patients withchronic fatigue syndrome have reduced absolutecortical blood flow. Clin Physiol Funct Imag 2006,
26:83-86
9. Nakahara R, Yoshiuchi K, Kumano H, et al:
Pro-spective study on influence of psychosocial
factors on glycemic control in Japanese patientswith type 2 diabetes. Psychosomatics. 2006, 47:
240-6.
10. Takimoto Y, Yoshiuchi K, Kumano H, Kuboki T:
Bulimia nervosa and abnormal cardiac repolarization. J Psychosom Res. 2006, 60:105-7.
11. Yoshida NM, Kumano H, Kuboki T: Does theAging Males' Symptoms scale assess major depressive dis-order?: a pilot study. Maturitas. 2006,
53:171-5
12. Slingsby BT, Akabayashi A. Live organ-donation
for islet transplantation. Lancet. 2005, 366:26-7.
13. Akabayashi A, Slingsby BT, Takimoto Y. Conflictof interest: a Japanese perspective. Camb Q
Healthc Ethics. 2005, 14:277-80
14. Yoshida NM, Yoshiuchi K, Kumano H, Sasaki T,
Kuboki T: Analysis of energy expenditure, endo-

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crine function, and autonomic nervous activity inanorexia nervosa patients during refeeding: A pilot study. Nutr Res 2005, 25:959-970
15. Kumano H, Haseme E, Fujimoto H, Matsuoka N,
Yoshiuchi K, Uchitomi Y, Akechi T, Nakano T,
Ko-bayashi M, Agari I, Kuboki T: Harmony-seeking and the risk of prostate cancer: aprebioptic study. J Psychosom Res 2005, 59:
16. 167-174
Sakamoto N, Martin RG, Kumano H, Kuboki T,
Al-Adawi S: Hikikomori, is it a culture-reactiveor culture-bound temperament?: Nidotherapy andclinical vignette from Oman. Int J Psychiatry Med
2005, 35:191-198
17. Kamijima K, Kuboki T, Kumano H, Burt T, Cohen
G, Arano I, Hamasaki T: A Placebo-controlled,
randomized withdrawal study of Sertraline forpanic disorder in Japan. Int Clin Psychopharm2005, 20:265-273
18. Hojo S, Yoshino H, Kumano H, Kakuta K, Miyata
M, Sakabe K, Matsui T, Ikeda K, Nozaki A, Ishikawa S: Use of QEESI© questionnaire for ascreening study in Japan. Toxicol Ind Health 2005,
21:113-124
19. Sakai Y, Kumano H, Nishikawa M, Sakano Y,
Kaiya H, Imabayashi E, Ohnishi T, Matsuda H,
Yasuda A, Sato A, Diksic M, Kuboki T: Cerebral
glucose me-tabolism associated with a fear network in panic disorder. NeuroReport 2005, 16:
927-931
20. Takaki J, Nishi T, Shimoyama H, Inada T,
Ma-tsuyama N, Kumano H, Kuboki T: Possible
interac-tive effects of demographic factors andstress coping mechanisms on depression and anxiety in mainte-nance hemodialysis patients. J
Psychosom Res 2005, 58:217-23
21. Miyawaki K, Sato A, Yasuda A, Kumano H, Kuboki T: Explicit knowledge and intention to learn
in se-quence learning: an ERP study. NeuroReport
2005, 16:705-708
22. Saito M, Kumano H, Yoshiuchi K, Kokubo N,
Oha-shi K, Yamamoto Y, Shinohara N, Yanagisawa Y, Sakabe K, Miyata M, Ishikawa S, Kuboki
T: Symp-tom profile of multiple chemical sensitivity in actual life. Psychosom Med 2005,
23. Sato
67:318-325
A, Yasuda A, Ohira H, Miyawaki K, Nishikawa M, Kumano H, Kuboki T: Effects of value
and reward mag-nitude on feedback negativity

and P300. NeuroReport 2005, 16:407-412

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Department ofTransfusion Medicine
Professor
Koki Takahashi, M.D., Ph.D.

Associate
Nelson H. Tsuno, M.D., Ph.D.,

Minoru Tanaka, M.D., Ph.D.,

Aki Kamijo, M.D, Ph.

Homepage

http://172.27.30.16/yuketsu/s-index.html

Introduction and Organization
The Transfusion Medicine service was establishedin 1949, as an internal provisional measure, and officially established in 1966. In 1984, Professor Hiroshi
Toyama assumed as the first Professor of the department. Professor Toyama greatly contributed to thefield of transfusion medicine, especially by publishing“Transfusion Medicine” (actually in its 3rd. edition),
which is the bible of transfusion medicine in Japan.
Other great contributions from the department are as
follows. Dr. Kazuo Okochi, ex-lecturer of the department, is the pioneer in the field of hepatitis research,
ex-Professor Takeo Juji clarified the mechanisms ofgraft-versus-host disease (GVHD), a serious posttransfusional complication, and the previous professor,
Professor Yoichi Shibata contributed enourmously tothe field of platelet immunology. In 1997, the Department of Transfusion Medicine was established as achair of the Division of Internal Medicine of the
Graduate School of Medical Sciences, the Universityof Tokyo.
Actually, the department is composed of 6 medical
doctors (4 full-time, and 2 partial-time), 10 laboratory
technicians, 1 nurse and 1 office assistant.

Clinical activities
The main activity of the department of Transfusion
Medicine is the control, preservation, and provision ofsafe blood products and their derivatives. The control
of all blood products in the hospital is centralized tothe department, which, in addition, provides information and orientation related to blood transfusion.
Transfusion-related laboratory tests and tests fortransfusion-transmitted infectious diseases are routine
practices of the department, which also actively takes
part in the diagnosis, prevention and treatment of adverse reactions and post-transfusion complications.
Collection, preservation and provision of autologous
blood are also important functions of the department,
where the outpatient clinic for autologous blood wasestablished in January 2006. At the outpatient clinic,
the first established in Japan, the transfusionist gives
consultation to the patients, prepares the adequate
blood collection schedule, takes the informed consent,
and performs the blood collection, according to thesurgeons’ needs. Additionally, immunotherapy ofcancer patients and patients with recurrent abortion,and collection and preservation of peripheral blood
stem cells are also performed.
I. Control and preservation of blood products and its
derivatives;
II. Laboratory tests
1) Blood typing and histocompatibility testing;2) Detection of anti-erythrocyte, anti-leukocyte
and anti-platelet antibodies;3) Detection of HBV antigens and antibodies, HCV,
HAB, ATLA and HIV antibodies;
4) HLA typing for bone marrow and organ trans-

155

plantation;
III. Clinical work
1) Pre-operative autologous blood collection andpreservation;2) Lymphocyte vaccination therapy for patientswith habitual abortion;3) Collection and preservation of peripheral blood
stem cells for transplantation;4) Dendritic cell-based cancer immunotherapy.
5) Anti-angiogenic cancer therapy.

Teaching activities
Sixth-year medical students are provided with practical courses focusing on clinical practice of bloodtransfusion and laboratory tests. Courses are given insmall groups of 6 students each, in a total of 18 groups
per year. The course lasts 3 days/week, including thefollowing subjects;
1) Visit to the laboratories of the department to understand the routine of a laboratory;
2) Introduction to the blood group types and theirimportance in transfusion medicine;3) Methodology of blood typing and compatibility
testing for transfusion;4) Methodology for screening of irregular antibodies,and their importance in transfusion practice;5) Introduction to the post-transfusional complications, their etiology, prevention and treatment.
6) The indications and techniques of autologous
blood collection and preservation;7) The techniques for peripheral blood stem cells(PBSCs) collection and preservation, as well as
their clinical application;8) The immunotherapy of cancer patients;
9) The recent advances in the field of blood transfusion, including the “New Blood Law”, and the recently revised “Indications of blood products” and“The principles of transfusion practice”.
10) One-day visit to the Japanese Red Cross Blood
Center, to learn the general process of blood donation and transfusion, including the types of blood
products, and their indications.

Research activities
Research on red cells, leukocytes, and platelets, thepost-tranfusional complications, transplantation immunology, immunotherapy, and stem cell biology are
the main themes of the department. Typing of blood
cells is performed by serological and DNA-based
methods. The HLA typing, which was introduced by
ex-Professor Takeo Juji, one of the pioneers of thisfield, is an essential test for stem cell and organ transplantations, and still continues as one of the most important research fields of the department. The
mixed-passive hemagglutination (MPHA) method, themost popular methodology for platelet serology inJapan, was developed by Professor Yoichi Shibata, theprevious professor, and its applicability is now extended for granulocyte as well as endothelial cell serology. Transplantation immunology, including stem
cell biology, and development of immunotherapeuticstrategies to treat cancer patients and patients withrecurrent abortion are also being performed. Recently,
development of new materials for medical use is being
researched. Following are the main themes.
1. Detection of platelet alloantigens and antibodies
and their role in the transfusion practice.
2. Diagnosis and prevention of post-transfusional
complications and thrombocytopenic purpura of
the newborn.
3. Clinical application of refrigerated and frozen-stored blood for autologous transfusion in
surgical patients.
4. Study on the mechanisms of transfusion-associated GVHD and its prevention.
5. Development of a new methodology for plateletcross-match.
6. Detection and characterization of anti-endothelial
cell antibodies, and study on their role in thepathogenesis of inflammatory and autoimmune
diseases, as well as in organ transplantation.
7. HLA and HPA genotyping.
8. Development of a new methodology for evaluationof platelet function.
9. Development of new strategies for the treatment ofcancer patients, by targeting the tumor vasculature.
10. Dendritic cell-based immunotherapy of cancer
patients.
11. Ex-vivo expansion of hematopoietic stem cells andtheir clinical application.
12. Development of new materials for medical use.

156

References
1. Asakage M, Tsuno NH, Kitayama J, Tsuchiya T,
Yoneyama S, Yamada J, Okaji Y, Kaisaki S, Osada
T, Takahashi K, Nagawa H. Sulforaphane induces
inhibition of human umbilical vein endothelial
cells proliferation by apoptosis. Angiogenesis.
2006; 9(2):83-91.
2. Okaji Y, Tsuno NH, Saito S, Yoneyama S, Tanaka
M, Nagawa H, Takahashi K. Vaccines targeting
tumour angiogenesis- -a novel strategy for cancer
immunotherapy. Eur J Surg Oncol. 2006; 32(4):363-703. Asakage M, Tsuno NH, Kitayama J, Kawai K,
Okaji Y, Yazawa K, Kaisaki S, Osada T, Watanabe
T, Takahashi K, Nagawa H. Early-outgrowth ofendothelial progenitor cells can function as antigen-presenting cells. Cancer Immunol Immunother. 2006; 55(6):708-16.
4. Y. Okaji, N. Tsuno, J. Kitayama, D. Sakurai, N.
Tsuchiya, S. Saito, K. Takegami, T. Tsuchiya, K.
Kawai, K. Yazawa. Effects of down-regulating theId genes in human colorectal cancer cells on earlysteps of haematogenous metastasis. European
Journal of Cancer, 42(5): 668-673, 2006

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Department of
Reproductive Endocrinology
Professor
Yuji Taketani

Osamu Tsutsumi

Associate Professor
Tetsu Yano

Lecturer
Koji Kugu

Mikio Momoeda

Toru Takeuchi

Toshihiro Fujiwara

Yutaka Osuga

Homepage
Organization
The Department of Reproductive Endocrinology isorganized by two professors, one associate professor
and five lecturers. All the staff members are taking
part in both clinical and research activities. For theclinical aspect, we are engaged with in-patient andout-patient care including the activities in the delivery
units.

Activities
In clinical section, we have an out-patient clinic for
infertility, gynecological endocrine diseases, genetic
counseling and assisted reproductive technologies(ART). We also perform minimal access surgery forendometriosis, uterine fibroid, benign tumor and soon.
We have a highly organized infertility clinic, where
every patient is systemically examined and after diagnosis of underlying infertility factor (s) appropriate
treatment is performed following our protocol. Once itturns out higher level of treatment is necessary, ART isapplied to such cases. We have been engaged in in
vitro fertilization and embryo transfer (IVF-ET) as amain axis of ART for eighteen years. Conventional
IVF-ET is mainly indicated to cases with tubal factor,

mild male factor, immunological factor or of unexplained infertility factor. In case of severe male factor
or other fertilization disorder intracytoplasmic sperm
injection (ICSI) is performed. Now we have about 250
OPU cycles of IVF-ET every year, which conventional IVF-ET and ICSI share almost equally. The
clinical pregnancy rate of conventional IVF-ET isaround 30% per embryo transfer cycle, which is comparable with that of ICSI. Other ART techniques suchas embryo cryopreservation and assisted hatching arealso performed.
In the field of gynecological surgery, we have been
constantly trying to minimize surgical invasion to patients as much as possible. With both of well-equipped
instruments and well-trained expertise, more than 90%of surgery cases for benign gynecological disorders
are operated endoscopically. These endoscopic surgeries include laparoscopic or laparoscopically assisted cyctectomy or salpingo-oophorectomy (228cases), laparoscopic hysterectomy or laparoscopicallyassisted vaginal hysterectomy (42 cases), laparoscopic
or laparoscopically assisted myomectomy (67 cases),diagnostic laparoscopy for infertility (29 cases)
laparoscopic surgery for ectopic pregnancy (15 cases),
hysteroscopic surgery (47 cases) and so on, whichmake a total of 372 cases.
[Each number of cases indicates per year base.]159

Primary care peri/post-menopausal women is becoming more important. We have already establishedthe primary care system for women focusing on climacteric syndrome and osteoporosis. Hormone replacement therapy (HRT) is employed for the purpose.
In basic research section, a couple of projects asfollows are under way, some of which have alreadyyielded interesting findings; 1) the mechanism of folliculogenesis and follicular apoptosis in the ovary, 2)
the functions of gynecologic hormones such as gonadotropins and ovarian steroids, 3) the analysis ofendometriosis, 4) effect of ovarian steroid hormoneson bone metabolism, and 6) effects of endocrine disrupters on the reproductive system.

References published in 2006
(1) Koga K. Osuga Y. Hiroi H. Oishi H. Kugu K.
Yano T. Taketani Y. Images in reproductive medicine. A case of giant cystic adenomyosis. Fertility& Sterility. 85(3):748-9, 2006.
(2) Harada M. Osuga Y. Takemura Y. Yoshino O.
Koga K. Hirota Y. Hirata T. Morimoto C. Yano T.
Taketani Y. Mechanical stretch upregulates
IGFBP-1 secretion from decidualized endometrial
stromal cells. [Journal Article] American Journalof Physiology - Endocrinology & Metabolism.
290(2):E268-72, 2006.
(3) Takeuchi T, Tsutsumi O, Ikezuki Y, Kamei Y,
Osuga Y, Fujiwara T, Takai Y, Momoeda M, Yano
T, Taketani Y. Elevated serum bisphenol A levels
under hyperandrogenic conditions may be caused
by decreased UDP-glucuronosyltransferase activity. Endocr J. 53(4):485-91, 2006.
(4) Fujimoto A, Mitalipov SM, Kuo HC, Wolf DP.
Aberrant genomic imprinting in rhesus monkey
embryonic stem cells. Stem Cells 24(3):595-603,
2006(5) Wada-Hiraike O, Hiraike H, Okinaga H, Imamov
O, Barros RP, Morani A, Omoto Y, Warner M,
Gustafsson JA Role of estrogen receptor beta inuterine stroma and epithelium: Insights from estrogen receptor beta-/- mice Proc Natl Acad Sci U
S A. 48: 18350-18355, 2006.
(6) Wada-Hiraike O, Warner M, Gustafsson JA New
developments in oestrogen signalling in colonicepithelium. Biochem Soc Trans 34(Pt6):1114-

1116,2006.
(7) Wada-Hiraike O, Imamov O, Hiraike H, Hultenby
K, Schwend T, Omoto Y, Warner M, Gustafsson
JA. Role of estrogen receptor beta in colonic epithelium. Proc Natl Acad Sci U S A. (8):2959-2964,
2006.
(8) Koga K, Takemura Y, Osuga Y, Yoshino O, Hirota
Y, Hirata T, Morimoto C, Harada M, Yano T, Taketani Y. Recurrence of ovarian endometrioma
after laparoscopic excision. Hum Reprod. 21(8):2171-2174, 2006.
(9) Yoshino O, Osuga Y, Koga K, Hirota Y, Hirata T,
Ruimeng X, Na L, Yano T, Tsutsumi O, Taketani Y.
FR 167653, a p38 mitogen-activated protein
kinase inhibitor, suppresses the development ofendometriosis in a murine model. J Reprod Immunol. 72(1-2):85-93, 2006.
(10)H. Oishi, H. Kitagawea, O. Wada, S. Takezawa, L.
Tora, M. kouzu-Fujita, I. Takada, T.Yano, J. Yanagisawa, S. Kato An hGCN5/TRRAP histone acetyltransferase complex co-activates BRCA1 transactivation function through histone modification.
J Biol Chem. 281(1):6-20,2006.
(11) Koyama Y, Rittling SR, Tsuji K, Hino K, Salincarnboriboon R, Yano T, Taketani Y, Nifuji A,
Denhardt DT, Noda M. Osteopontin deficiency
suppresses high phosphate load-induced bone loss
via specific modulation of osteoclasts. Endocrinology. 147(6):3040-3049,2006.
(12) Hirota Y, Osuga Y, Koga K, Yoshino O, Hirata T,
Morimoto C, Harada M, Takemura Y, Nose E,
Yano T, Tsutsumi O, Taketani Y. The expression
and possible roles of chemokine CXCL11 and its
receptor CXCR3 in the human endometrium. J
Immunol.177(12):8813-8821,2006.
(13) Takemura Y, Osuga Y, Yamauchi T, Kobayashi M,
Harada M, Hirata T, Morimoto C, Hirota Y, Yoshino O, Koga K, Yano T, Kadowaki T, Taketani Y.
Expression of adiponectin receptors and its possible implication in the human endometrium. Endocrinology. 147(7):320303210,2006.

160

Department of
Gynecologic Oncology
Associate

Professor

Tetsu Yano

Lecturer
Toshiharu Yasugi

Homepage
Organization
The Department of Gynecologic Oncology is organized by one associate professor and one lecturer,
being directed practically by Professor Yuji Taketani,
the Chairman of the Department of Obstetrics andGynecology. The staff members are taking part in bothclinical and research activities, as well as teachingactivities, with 18 associates of the University of Tokyo Hospital. For the clinical aspect, they are engaged
with in-patient and out-patient care.

Activities(1) Oncology research
In our division, the pathogenesis of uterine cervical
can-cer has been investigated these two decades. To
identify the risk factors for cervical intraepithelial
neoplasia (CIN), we reanalysed the data from our previous case-control study by adjusting for humanpapillomavirus (HPV) antibodies. Unlike our previous
study based only on HPV DNA, smoking and Chlamydia trachomatis in-fection were revealed as significant risk factors for CIN after adjustment for HPV
antibodies. The enhanced on-cogenicity of particular
human papillomavirus type 16 (HPV16) E6 variants is
population-dependent, implying the involvement ofadditional genetic cofactors. This study was designed
to investigate the association between E6 variants andhuman leukocyte antigen (HLA) poly-morphism
within a Japanese population. Fifty-seven women with

HPV16-positive cervical cancer were ana-lyzed for E6
sequence variation and its relationship to HLA class II
alleles. Compared with local controls (n = 138) andpublished controls (n = 916), DRB1*1501 andDQB1*0602 frequencies were significantly increased
among patients with HPV16 E6 prototype (n = 11).
Ad-ditionally, DRB1*1502 was positively associatedwith a particular E6 variant designated D25E (n = 25),
although we could not find a significant association
between HLA class II alleles and L83V variants (n =16). Our observa-tions suggest that a specific match
between E6 variant proteins and HLA types may contribute to HPV16-related cervical carcinogenesis.
Studies of virus neutralization by antibody are prerequi-site for development of a prophylactic vaccine
strategy against HPVs. To determine whether neutralizing anti-bodies (NAs) against HPV16 is responsible
for a higher regression rate of low-grade cervical intraepithelial neo-plasia (CIN1), we investigated an
association between the presence of the NAs and thefate of the HPV16-related CIN1. The incidence of thepresence of the NAs in the women with a
non-pathological cervix (85.7%) was sig-nificantly
higher than in the CIN1 cases (21.5%), the CIN2/3
cases (15.7%), and the cervical cancer cases (0%)(p<0.0001). The regression of the CIN1 lesion wasclosely associated with the presence of the N As
(p=0.0002). The presence of the NAs was associatedwith low-level copy number of the viral DNA relative
to the NA-negative group (p=0.05). The presence of
the NAs against HPV16 was associated with a higher

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regression rate of HPV-related CIN1 lesions. The NAsseem to have a role in deterring HPV-related cervicallesions from progressing to CIN2/3 by inhibiting theinfection with de novo replicated HPV. Then we designed a pla-cebo-controlled trial in healthy adults toevaluate the safety and immunogenicity of a synthetic
peptide con-sisting of the aa 108-120 of HPV16 L2(L2-108/120) region, because this region contains across-neutralization epitope against genital HPV.. A
total of 13 volunteers were given nasal inoculations
with 0.1 (n=5) or 0.5mg (n=5) doses of the peptides orplacebo (n=3) without adjuvant at weeks 0, 4, and 12.
Sera were collected before inoculation and at 6, 16
and 36 weeks. The inoculation caused no serious local
and systemic complications. The inoculation generated anti-L2 antibodies binding to both HPV16 and 52
L1/L2-capsids in four of the five recipi-ents in the
0.5mg group. Sera of the four recipients showed neutralizing activities against HPV16 and 52. Serologicalresponses to the peptides were not found in the 0.1mggroup and the placebo group recipients. This study
suggests the L2-108/120 peptide is tolerable in humans and has the potential as a broad-spectrum
pro-phylactic vaccine against genital HPV.
We also investigated interacting proteins with the
HPV E6 protein. Recently, a LAP protein, scribble,
was iden-tified in Drosophila epithelia as a basolateralprotein that controls the apical-basolateral polarity.
Loss of scribble causes disorganisation and overgrowth of the epithelia. Scribble has a human homologue, human scribble (hScrib), which is a substrate ofubiquitin-mediated deg-radation by human papillomavirus E6 and the E6AP ubiquitin-protein ligase. In
the present study, we revealed that hScrib localised tothe basolateral regions of the epithelial cell line
MDCK and human uterine cervical epithelial tissues
by immunofluorescence. Human scrib-ble colocalised
rather with the adherens junction protein E-cadherin,
but not with the tight junction protein ZO-1. Histochemical analysis showed a dramatic decrease in theexpression of hScrib with the progression of disease
from normal uterine cervical tissues to invasive cervical can-cers through the precursor lesions. In contrast, the ex-pression of hScrib was retained in thethroughout epithe-lial layer of the HPV-negative cervical high-grade squamous intraepithelial lesions(H-SIL). Although quantitative RT-PCR revealed nosignificant downregu-lation of hScrib mRNA expression in the H-SIL, it re-vealed a clear downregulationin the invasive cancers. These results suggest the possibility that degradation by HPV E6 is one of thecausal roles for the progressive decrease of hScrib
expression during the disease pro-gression fromlow-grade squamous intraepithelial lesions to H-SIL,
and a cooperative role of downregulation of hScribmRNA expression and ubiquitin-mediated degra-dation of hScrib by E6 and E6AP led to the complete decrease of hScrib expression during the processof car-cinogenesis from H-SIL to invasive cancer.
These data underscore the importance of hScrib in theconstruction of tissue architecture and prevention ofcancer develop-ment.
Another basic research is focused on analysis oftumor suppressor genes in gynecological malignancies
as following.
1 Human Scribble
Recently, a LAP protein, scribble, was identi-fied in
Drosophila epithelia as a basolateral protein that controls the apical-basolateral polarity. Loss of scribble
causes disorganisation and overgrowth of the epithelia.
Scribble has a human homologue, human scribble(hScrib), which is a substrate of ubiquitin-mediateddeg-radation by human papillomavirus E6 and theE6AP ubiquitin-protein ligase. In the present study,
we re-vealed that hScrib localised to the basolateralregions of the epithelial cell line MDCK and humanuterine cervical epithelial tissues by immunofluorescence. Human scrib-ble colocalised rather with theadherens junction protein E-cadherin, but not with thetight junction protein ZO-1. Histochemical analysis
showed a dramatic decrease in the expression of
hScrib with the progression of disease from normal
uterine cervical tissues to invasive cervical cancers
through the precursor lesions. In contrast, the expression of hScrib was retained in the throughout epithelial layer of the HPV-negative cervical high-grade
squamous intraepithelial lesions (H-SIL). Althoughquantitative RT-PCR revealed no significant downregu-lation of hScrib mRNA expression in the H-SIL,
it re-vealed a clear downregulation in the invasivecancers. These results suggest the possibility that
degradation by HPV E6 is one of the causal roles forthe progressive decrease of hScrib expression during
the disease pro-gression from low-grade squamous

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intraepithelial lesions to H-SIL, and a cooperative roleof downregulation of hScrib mRNA expression andubiquitin-mediated degra-dation of hScrib by E6 andE6AP led to the complete decrease of hScrib expression during the process of car-cinogenesis from H-SIL
to invasive cancer. These data underscore the importance of hScrib in the construction of tissue architecture and prevention of cancer develop-ment.
Drosophila discs large (Dlg) is one of neoplas-tic
tumor suppressors, which genetically links to scribble.
E6 also targets human Dlg (hDlg) for ubiquitin-mediated degradation. Ubiquitin-protein ligase
involved in this process has not been identified thus
far. Here we inves-tigated mechanism underlying
degradation of three target proteins of E6, hScrib,
hDlg, and p53 by using eighteen HPV 16 E6 mutants
with single amino acid substitution. In vitro degradation ability of each E6 mutant was equivalent for thesetumor suppressors. We investigated whether E6AP is
involved in ubiquitin-mediated degra-dation of hDlg.
In vitro binding assay revealed that hDlg formed ternary complex with E6-E6AP complex. The ability of
E6 mutants to degrade these tumor suppressors wascorrelated with their ability to interact with E6AP.
Furthermore, hDlg was targeted for in vitro ubiquitina-tion in the presence of both E6 and E6AP. These
data revealed that E6AP is extensively involved in theubiq-uitin-mediated degradation of E6-dependent
substrates as a cellular E3 ubiquitin-protein ligase.
Human Scribble, classified as a LAP protein containing leucine-rich repeats and PDZ domains, interacts with E6 through its PDZ domains and C-terminal
PDZ do-main-binding motif of E6 protein. Interaction
between human Discs Large (hDlg), which is a substrate of E6 for the ubiquitin-mediated degradation,
and adenomatous polyposis coli (APC) has beenshown. Here, we investi-gated whether hScrib and
APC interact with each other in vitro and in vivo. Interaction between hScrib and APC is mediated by the
PDZ domains 1 and 4 of hScrib and C-terminal PDZ
domain-binding motif of APC. Human Scribble
co-localized with APC at the synaptic sites of hippocampal neuron and at the tip of membrane protru-sionin the epithelial cell line. Interference of the interac-tion between hScrib and APC caused disruptionof ad-herens junction. Knockdown of hScrib expression by RNAi disrupts localization of APC at the ad-herens junc-tion. These data suggest that hScrib may
participate in the hDlg-APC complex through its PDZ
domains and regulate cell cycle and neural function by
associating with APC.
Drosophila tumor suppressor Scribble has been
identified as an apical-basolateral polarity determinant
in epithelia. A human homolog of Drosophila Scribble,
human Scrib-ble (hScrib), has been identified as aprotein targeted by human papillomavirus E6 for theubiquitin-mediated degradation dependent on E6AP, acellular ubiq-uitin-protein ligase. Human Scribble isclassified as a LAP protein, having leucine-rich repeats (LRRs) and PDZ domains. We investigatedwhether hScrib, which is thought to have a role in polarity determination based on the data of its Drosophila homolog, is involved in cell-cycle regulation andproliferation control of epithe-lia. Transfection of
hScrib inhibits cell-cycle progression from G1 to S
phase, and it up- and down-regulates ex-pression of
adenomatous polyposis coli and cyclins A and D1,
respectively. Knockdown of hScrib expression by
siRNA leads to cell-cycle progression from G1 to S
phase. We explored functional domain mapping toreveal which domains of hScrib are critical for its
cellular pro-liferation control and localization at thebasolateral membrane. We found that LRRs and PDZ
domain 1 are indispensable for hScrib to inhibit cell
growth by block-ing cell-cycle progression and tokeep its proper local-ization. These data indicate thatbasolateral membrane localization of hScrib is closely
related to its prolifera-tion control. Our findings suggest the possibility that hScrib is involved in signaltransduction to negatively regulate cell proliferation
by localizing at the basolateral membrane of epithelial
cells through LRRs and PDZ domains.
We also investigated which E3 ubiquitin-protein ligase is involved in the ubiquitin-mediated degradationof hDlg. Human scribble (hScrib), which was identified as sub-strate of human papillomavirus (HPV) E6
for ubiq-uitin-mediated degradation dependent on
ubiq-uitin-protein ligase E6AP, is a human homolog ofDro-sophila neoplastic tumor suppressor scribble, inwhich mutation causes loss of polarity and overgrowthof epi-thelia. Drosophila discs large (Dlg) is one ofneoplastic tumor suppressors, which genetically links
to scribble. E6 also targets human Dlg (hDlg) for
ubiquitin-mediated degradation. Ubiquitin-protein

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ligase involved in this process has not been identified
thus far. Here we inves-tigated mechanism underlying
degradation of three target proteins of E6, hScrib,
hDlg, and p53 by using eighteen HPV 16 E6 mutants
with single amino acid substitution. In vitro degradation ability of each E6 mutant was equivalent for thesetumor suppressors. We investigated whether E6AP is
involved in ubiquitin-mediated degra-dation of hDlg.
In vitro binding assay revealed that hDlg formed ternary complex with E6-E6AP complex. The ability of
E6 mutants to degrade these tumor suppressors wascorrelated with their ability to interact with E6AP.
Furthermore, hDlg was targeted for in vitro ubiquitina-tion in the presence of both E6 and E6AP. These
data revealed that E6AP is extensively involved in theubiq-uitin-mediated degradation of E6-dependent
substrates as a cellular E3 ubiquitin-protein ligase.
2 PTEN
Although the mutation of PTEN, a tumor suppressor, is known to be involved in tumorigenesis of
en-dometrioid adenocarcinomas of the endometrium
and ovary, the role of PTEN alteration in endometrioid
ade-nocarcinoma of the cervix remains to be investigated. To elucidate the molecular pathogenesis of cervical adeno-carcinoma and adenosquamous carcinoma,
and in par-ticular to examine the potential role of
PTEN mutation in endometrioid-type cancer of thecervix, we analyzed 32 cervical adeno- or
adenosquamous carcinomas (8 endo-metrioid adenocarcinomas, 14 mucinous adenocarcino-mas and 10
adenosquamous carcinomas) for PTEN mu-tations and
HPV infections. PTEN mutation was detected in 2 of
8 (25.0%) endometrioid cases, 2 of 14 (14.3%) mucinous cases, and none of 10 (0%) adenosquamous cases.
HPV DNA was detected in 11 out of 18 (61.1%)
PTEN wild-type adenocarcinomas and 8 out of 10(80.0%) adenosquamous carcinomas. Among 11
HPV-negative adenocarcinomas, 40.0% (2/5) endometrioid cases and 33.3% (2/6) mucinous cases wereshown to be PTEN mutated, while no cases (0/21)
were PTEN-mutant in the remainder (i.e.
adenosquamous car-cinomas and HPV-positive adenocarcinomas). The cur-rent observations suggest that
PTEN mutation is fre-quently detected in HPVnegative adenocarcinomas of the cervix and the mostprevalent occurrence of PTEN mutation in endometrioid subtype is keeping with endo-metrial andovarian carcinomas.
Next, we analyzed involvement of PTEN in treatment of endometrial cancer. Young patients with complex atypical hyperplasia (CAH) or stage Ia, G1 adenocarcinoma (IaG1) of the endometrium, who desire
to preserve fertility, can select the conservative therapy by oral progestin, medroxyprogesterone acetate(MPA). However, conservative treatments involve
potential risks of progression and recurrence. In an
attempt to find out molecular markers for sensitivity
to MPA, we performed immunohistochemical analysis
of PTEN, phospho-Akt, p53, ER and PgR in
MPA-treated 31 cases with CAH or IaG1. Eleven of
12 cases (92%) with CAH and 15 of 19 cases (79%)
with IaG1 demonstrated an initial complete response,while five patients underwent hysterectomy due to no
response. Four of 11 responders (36%) with CAH andfive of 15 responders (33%) with IaG1 later developed
relapse. Five of nine patients (56%) with CAH andthree of 11 patients (27%) with IaG1 became pregnant
after infertility treatment. Immunohistochemi-cal
analysis revealed that phospho-Akt expression was
significantly decreased by MPA administration(p=0.002). Furthermore, combination of two factors,
weak phosho-Akt or PTEN-null expression, wasfound to be significantly associated with receiving
hysterectomy (p=0.04), while each factor showed atrend without sta-tistical significance (p=0.07 and 0.2,
respectively). Strong expression of both ER and PgRsignificantly cor-related with successful pregnancy
after infertility treat-ment following complete response to MPA (p=0.02). Our observations in vivo
suggest that anti-tumor action of MPA may be mediated by dephosphorylation of Akt, and that immunohistochemical evaluation of phospho-Akt and PTEN
may be able to predict the outcome of MPA therapy.
3 SFRP1 gene
The SFRP1 gene on chromosome 8p11.2 en-codes a
Wnt signaling antagonist, and was recently demonstrated to be a new tumor suppressor that is inactivated by promoter methylation in human colon cancers. Here, we analyzed promoter methylation of the
SFRP1 gene in human ovarian cancers, in which lossof het-erozygosity in 8p is frequently observed andinvolve-ment of the Wnt signaling pathway has beensuggested. Methylation-specific PCR (MSP) analysis
showed that four of 13 ovarian cancer cell lines and164

two of 17 pri-mary ovarian cancers had methylated
SFRP1, while an immortalized ovarian epithelial cellline, HOSE, and seven ovarian endometrial cyst samples did not. In the four ovarian cancer cell lines withthe methylation, SFRP1 was not expressed at all as
determined by quan-titative RT-PCR analysis. These
results show that SFRP1 is inactivated by promoter
methylation in human ovarian cancers, as well as colon cancers.
4 hMSH2
The DNA mismatch repair gene is a key regu-lator
in the elimination of base-base mismatches and insertion/deletion loops (IDLs). Human MutS homo-logue
2 (hMSH2), originally identified as a human homologue of the bacterial MutS, is a tumour suppressor
gene frequently mutated in hereditary non-polyposis
co-lorectal cancer. Hereditary non-polyposis colorectal cancer is characterised by the early onset of colorectal cancer and the development of extracoloniccancers such as endometrial, ovarian, and urologicalcancers. Oestro-gen receptor (ER) alpha and beta aremembers of a nu-clear receptor (NR) superfamily.
Ligand-dependent transcription of ER is regulated by
the p160 steroid re-ceptor coactivator family, the thyroid hormone recep-tor-associated proteins/the vitamin D receptor-interacting proteins (TRAP/DRIP)
mediator complex, and the TATA box-binding protein(TBP)-free TBP associated factor complex (TFTC)
type histone acetyltransferase complex. We identified
the interaction between ER al-pha/beta and hMSH2.
Immunoprecipitation and glu-tathione-S-transferase
pull-down assay revealed that ER alpha and hMSH2
interacted in a ligand-dependent manner, whereas ER
beta and hMSH2 interacted in a ligand-independent
manner. Oestrogen receptor al-pha/beta bound tohMSH2 through the hMSH3/hMSH6 interaction domain of hMSH2. In a transient expression assay,
hMSH2 potentiated the transactivation function ofliganded ER alpha, but not that of ER beta. These results suggest that hMSH2 may play an important role
as a putative coactivator in ER alpha dependent gene
expres-sion.
(2) Clinical oncology
To compare treatment outcome results of conventional surgery vs. radiotherapy (RT) for carcinomaof the uterine cervix. A retrospective analysis was

con-ducted of 152 patients with uterine cervical cancer radi-cally treated with surgery or high dose-rate
intracavitary brachytherapy (HDR-ICBT) with orwithout external RT from June 1991 to May 2004. The
median follow-up time was 43.5 months (range,
1.0-130.0 months). The median age was 53 years(range, 25-81 years). There were 13 patients (9%) instage IA, 52 (34%) in stage IB, 24 (16%) in stage IIA,
and 63 (41%) in stage IIB. The conventional surgery
group included 115 patients (76%) who underwent
hysterectomy with pelvic lymph node dissection. Of
these, 72 (63%) received postoperative radiotherapy.
Thirty-seven patients (24%) were assigned to the RT
group. Of these, 14 (38%) received chemoradiotherapy. Three patients with stage I received
ICBT-alone without external beam irradiation.
RESULTS: The 5-year cause-specific survival (CSS)
rates for surgery and RT were 79.9% and 82.3%, respec-tively; the difference between these two treatments was not statistically significant (P = 0.8524).
The differences in the survival rates between the twotreatments for each of the stage I or stage II patientswere also not statisti-cally significant (P = 0.8407 forstage I and P = 0.6418 for stage II). This retrospective
study suggests that RT results in compatible survivalwith conventional surgery for patients with stage I-II
cervical carcinoma.

References from April 2005 to
March 2007
1) Minaguchi T. Yoshikawa H. Nakagawa S. Ya-sugi
T. Yano T. Iwase H. Mizutani K. Shiromizu K.
Ohmi K. Watanabe Y. Noda K. Nishiu M. Nakamura Y. Taketani Y. Association of PTEN mutation with HPV-negative adenocarcinoma of theuterine cervix. Cancer Letters. 210(1):57-62, 2004
Jul 8.
2) Kawana K. Nakayama M. Yasugi T. Ishiwata M.
Marumo G. Sakai M. Takeshima T. Kozuma S.
Tsutsumi O. Taketani Y. Differential clinicalmani-festations of congenital cytomegalovirus infection between dizygotic twins: a case report.
American Journal of Perinatology. 21(7):383-6,
2004 Oct.
3) Onda T. Yoshikawa H. Yasugi T. Yamada M. Matsumoto K. Taketani Y. Secondary cytoreductive

165

surgery for recurrent epithelial ovarian carcinoma:
proposal for patients selection. British Journal ofCancer. 92(6):1026-32, 2005 Mar 28.
4) Wada-Hiraike O. Yano T. Nei T. Matsumoto Y.
Nagasaka K. Takizawa S. Oishi H. Arimoto T.
Naka-gawa S. Yasugi T. Kato S. Taketani Y. The
DNA mismatch repair gene hMSH2 is a potent
coactivator of oestrogen receptor alpha. British
Journal of Cancer. 92(12):2286-91, 2005 Jun 20.
5) Oda K. Stokoe D. Taketani Y. McCormick F. Highfrequency of coexistent mutations of PIK3CA andPTEN genes in endometrial carcinoma. Cancer
Research. 65(23):10669-73, 2005 Dec 1
6) Matsumoto K. Yasugi T. Oki A. Fujii T. Nagata C.
Sekiya S. Hoshiai H. Taketani Y. Kanda T.
Ka-wana T. Yoshikawa H. IgG antibodies to
HPV16, 52, 58 and 6 L1-capsids and spontaneous
regression of cervical intraepithelial neoplasia.
Cancer Letters. 231(2):309-13, 2006 Jan 18.
7) Arimoto T, Nakagawa S, Yasugi T, Yoshi-kawa H,
Kawana K, Yano T, Taketani Y.
Treatment with paclitaxel plus carboplatin, alone orwith irradiation, of advanced or recurrent endometrial carci-noma. Gynecol Oncol. 2007
Jan;104(1):32-5. Epub 2006 Sep 22.
8) Nagasaka K, Nakagawa S, Yano T, Takizawa S,
Matsumoto Y, Tsuruga T, Nakagawa K, Minaguchi T, Oda K, Hiraike-Wada O, Ooishi H, Yasugi T,
Taketani Y.
Human homolog of Drosophila tumor suppressor
Scrib-ble negatively regulates cell-cycle progression from G1 to S phase by localizing at the basolateral membrane in epithelial cells.
Cancer Sci. 2006 Nov;97(11):1217-25.
9) Miura S, Matsumoto K, Oki A, Satoh T, Tsunoda
H, Yasugi T, Taketani Y, Yoshikawa H.
Do we need a different strategy for HPV screening
and vaccination in East Asia?
Int J Cancer.
2006 Dec 1;119(11):2713-5.
10) Takizawa S, Nagasaka K, Nakagawa S, Yano T,
Nakagawa K, Yasugi T, Takeuchi T, Kanda T,
Hui-bregtse JM, Akiyama T, Taketani Y.
Human scribble, a novel tumor suppressor identified as a target of high-risk HPV E6 for ubiquitin-mediated deg-radation, interacts with adenomatous polyposis coli.
Genes Cells. 2006 Apr;11(4):453-64.

11) Matsumoto Y, Nakagawa S, Yano T, Takizawa S,
Nagasaka K, Nakagawa K, Minaguchi T, Wada O,
Ooishi H, Matsumoto K, Yasugi T, Kanda T, Huibregtse JM, Taketani Y.
Involvement of a cellular ubiquitin-protein ligase
E6AP in the ubiquitin-mediated degradation ofextensive sub-strates of high-risk human papillomavirus E6.
J Med Virol. 2006 Apr;78(4):501-7.
12) Oda K, Stokoe D, Taketani Y, McCormick F.
High frequency of coexistent mutations of
PIK3CA and PTEN genes in endometrial carcinoma. Cancer Res. 2005 Dec 1;65(23):10669-73.

166

Department of Perinatal Medicine
Associate Professor
Shiro Kozuma

Tomoyuki Fujii

Lecturer
Yoshimasa Kamei

Homepage

http://www.iiosan.umin.jp/index.htm

Organization
The Department of Perinatal Medicine is organizedby two associate professors and one lecturer, being
directed practically by Professor Yuji Taketani, thechairman of the Department of Obstetrics and Gynecology. All the staff members are taking part in boththe clinical and research activities, as well as theteaching activities, with 15 associates of the University of Tokyo Hospital. For the clinical aspect, they
are engaged with in-patient and out-patient care including the activities in the delivery units.

Activities
The clinical service for perinatology in the University of Tokyo Hospital consists of out-patient clinic
and the Delivery Unit. [See Delivery Unit of the University of Tokyo Hospital]
By the advance of the techniques for prenatal diagnosis of fetal growth and congenital malformations,the area of fetal medicine is enlarging. Strict measurement of fetal growth during pregnancy has madethe accurate diagnosis of intrauterine growth retardation possible. New techniques like fetal blood sampling and three- dimensional ultrasonography havebeen introduced into clinical service. The subjects ofstudies were focused on “fetus” and “ultrasound” inperinatology and medical engineering research group.
Fetal behavior, particularly breathing movements andsleep-wakefulness cycle were studied with ultrasoundin human fetuses. Studies were done to investigate
mechanism of fetal brain damage by repeated cord

occlusion in sheep. The effect of brain damage on fetal behavior was also studied.
Recurrent spontaneous abortion (RSA) is diagnosed
by a history of three times or more spontaneous abortions in the first trimester. Our “RSA clinic” opens
once a week. About 120 new couples with RSA visit
our hospital in a year. The patients are checked several
risk factors of RSA, such as anatomical, chromosomal,
hormonal, biological, or autoimmune factors. To RSA
patients with autoimmune factors, especially with antiphospholipid antibodies, anticoagulation therapy is
performed. For the low risk group, low dose aspirin isadministered. Heparin injection is performed for thehigh risk group, for instance, patients with successive
intrauterine fetal death during the second or third trimester of pregnancy, or those with beta-2 glycoprotein
I dependent anticardiolipin antibody. Further to RSA
patients with unknown etiology, the immunotherapy
with her husband’s lymphocyte inoculation is indicated. The inoculation is usually performed four to six
times in every two or three weeks. In our clinic, after
the immunotherapy, their pregnancy outcomes haveextremely improved in these 10 years. Now the successful reproductive rate has achieved over 80%.

References from April 2005 to
March 2007
(1) Kanamori Y. Hashizume K. Sugiyama M. Tomonaga T. Goishi K. Yokoyama Y. Igarashi T.
Kikuchi A. Kawana Y. Kozuma S. Taketani Y. A
case of intrapericardial diaphragmatic hernia witha massive pericardial effusion: fetal diagnosis and167

therapy. Journal of Pediatric Surgery. 40(11):e43-5, 2005
(2) Matsubara K. Nagamatsu T. Fujii T. Kozuma S.
Taketani Y. Lymphokine-activated killer cells induced from decidual lymphocytes reduce the angiogenic activity of trophoblasts by enhancing therelease of soluble fms-like tyrosine kinase-1 fromtrophoblasts: an implication for the pathophysiology of preeclampsia. Journal of Reproductive
Immunology. 68(1-2):27-37, 2005
(3) Kikuchi A. Unno N. Horikoshi T. Shimizu T.
Kozuma S. Taketani Y. Changes in fractal features of fetal heart rate during pregnancy. Early
Human Development. 81(8):655-61, 2005
(4) Hayashi A. Kikuchi A. Matsumoto Y. Tatematsu
M. Horikoshi T. Ogiso Y. Unno N. Massive cystic
lymphangiomas of a fetus. Congenital Anomalies.
45(4):154-6, 2005
(5) Hayashi A. Kikuchi A. Joshita N. Matsumoto Y.
Tatematsu M. Horikoshi T. Ogiso Y. Unno N.
Monochorionic triplet pregnancy complicated bysevere fetofetal transfusion. Journal of Obstetrics& Gynaecology Research. 31(5):414-20, 2005
(6) Horikoshi T. Kikuchi A. Matsumoto Y. Tatematsu
M. Takae K. Ogiso Y. Nakayama M. Unno N.
Fetal hydrops associated with congenital pulmonary myofibroblastic tumor. Journal of Obstetrics& Gynaecology Research. 31(6):552-5, 2005
(7) Horikoshi T. Kikuchi A. Tatematsu M. Matsumoto Y. Hayashi A. Unno N. Two cases of a fetus
with sirenomelia sequence. Congenital Anomalies.
45(3):93-5, 2005
(8) Yoshida S. Furue M. Nagamine K. Abe T. Fukui
Y. Myoishi Y. Fujii T. Okamoto T. Taketani Y.
Asashima M. Modulation of activin A-induced
differentiation in vitro by vascular endothelial
growth factor in Xenopus presumptive ectodermal cells. In Vitro Cellular & Developmental Biology. Animal. 41(3-4):104-10, 2005
(9) Yoshida S. Kikuchi A. Naito S. Nakamura H.
Hayashi A. Noguchi M. Kondo Y. Nakamura T.
Giant hemangioma of the fetal neck, mimicking ateratoma. Journal of Obstetrics & Gynaecology
Research. 32(1):47-54, 2006.
(10) Hanafusa N. Noiri E. Yamashita T. Kondo Y. Suzuki M. Watanabe Y. Kanai T. Miyashita E. Tsuno
NH. Fujii T. Kozuma S. Takahashi K. Taketani Y.

Nakao A. Fujita T. Successful treatment by double filtrate plasmapheresis in a pregnant woman
with the rare P blood group and a history of multiple early miscarriages. Therapeutic Apheresis &Dialysis. 10(6):498-503, 2006(11) Nagamatsu T. Fujii T. Matsumoto J. Yamashita T.
Kozuma S. Taketani Y. Human leukocyte antigen
F protein is expressed in the extra-villous trophoblasts but not on the cell surface of them.
American Journal of Reproductive Immunology.
56(3):172-7, 2006.
(12) Kusumi M. Yamashita T. Fujii T. Nagamatsu T.
Kozuma S. Taketani Y. Expression patterns oflectin-like natural killer receptors, inhibitory
CD94/NKG2A, and activating CD94/NKG2C on
decidual CD56bright natural killer cells differ
from those on peripheral CD56dim natural killer
cells. Journal of Reproductive Immunology.
70(1-2):33-42, 2006.
(13) Komatsu A. Kozuma S. Hyodo H. Horikoshi T.
Sakamaki K. Kikuchi A. Kamei Y. Fujii T. Taketani Y. Changes in umbilical arterial blood flowby an intraamniotic distilled water infusion.
Journal of the Society for Gynecologic Investigation. 13(3):166-73, 2006.
(14) Kikuchi A. Shimizu T. Hayashi A. Horikoshi T.
Unno N. Kozuma S. Taketani Y. Nonlinear analyses of heart rate variability in normal andgrowth-restricted fetuses. Early Human Development. 82(4):217-26, 2006.

170

Department ofPediatrics, Department ofDevelopmental Pediatrics
Professor
Takashi Igarashi, M.D.,Ph.D.

Associate Professor
Masashi Mizuguchi, M.D., Ph.D.
Takashi Sekine, M.D., Ph.D.

Lecturer
Hiroshi Watanabe, M.D., Ph.D.
Hitoshi Kato, M.D., Ph.D.
Masaru Takamizawa, M.D., Ph.D.
Junko Takita, M.D., Ph.D. (Department of Cell Therapy and Transplantation Medicine)

Associate
Kazuhiko Shibuya, M.D., Ph.D.,
Hirotsugu Kano, M.D., Ph.D.,
Keiji Goishi, M.D.,
Masakazu Mimaki, M.D., Ph.D.,
Satsuki Kakiuchi M.D.,
Ayaka Furuya M.D.,(As of Dec. 1, 2006)

Homepage

Komei Ida, M.D.,
Shinya Tsuchida, M.D.,
Jun Inatomi, M.D., Ph.D.,
Akio Ishiguro, M.D.,
Youichiro Hirata M.D.,

Yoshitaka Yokoyama, M.D.,
Katsuyoshi Ko, M.D.,
Hiroshi Ono, M.D.,
Kan Takahashi, M.D.,
Hideki Hoshino M.D.,

http://square.umin.ac.jp/ped/

Introduction and Organization
The former Department of Pediatrics developed into
Department of Pediatrics and Department of Developmental Pediatrics, which comprise subgroups of theGroup of Reproductive, Developmental and Aging
Medicines, Graduate School of Medicine, The University of Tokyo.
Our staff consist of 1 professor, 2 associate professors, 4 lecturers, 3 senior associates, 13 associates, 11senior residents, 1 research fellow, 11 graduate students and 2 foreign pediatricians as of Dec 1, 2006.
The outpatient clinic of our department is locatedon the second floor of the outpatient clinic building.
The inpatient ward and conference rooms are locatedon the second floor of the inpatient clinic building A.
Offices are on the second and third floors of the East
Research Building. Our laboratories are located on thesecond, third and fourth floors of the Research Building of Internal Medicine and on the second and third
floors of the East Research Building.

Clinical activities
We have specialized outpatient clinics covering allpediatric fields in addition to general pediatrics. In the171

pediatric and pediatric surgery ward, there are 96 beds
including 9 beds in the neonatal intensive care unit
(NICU), 6 beds in the growth care unit (GCU) and 26
beds in the high care unit (HCU). In NICU we aretaking care of small premature babies weighing 400g
to 3,000g with or without various complications. A
variety of patients with diseases such as hematological/oncological disorders (acute leukemia, neuroblastoma, Ewing sarcoma, osteosarcoma, brain tumors,etc.), cardiac disorders (congenital heart diseases andKawasaki disease), neuromuscular disorders, immunological/allergic disorders (common variable immunodeficiency, chronic granulomatous disease, bronchial asthma, etc.), renal and urinary tract diseases(nephrotic syndrome, chronic glomeluronephritis,
purpura nephritis and renal and urinary tract anomalies), endocrinological disorders, metabolic disorders
and psychosomatic diseases are admitted in the wards.
So far 70 patients received hematopoietic stem celltransplantation. There are patients with severe combined
immunodeficiency,aplastic
anemiamyelodysplastic syndrome, acute lymphocytic leukemia with high-risk features, acute myelogenous leukemia, non-Hodgkin lymphomas, disseminatedneuroblastoma and brain tumors.
We have a clinical conference and a grand round in
the Tuesday afternoon. Jeffrey C. Fahl, M.D., Professor of Pediatrics, Division of Pediatric Gastroenterology and Nutrition attended this conference and gave
several lectures from January to April, 2006. He also
opened special education course for junior doctors invery Friday evening during that time. In the Thursday
evening, we have a special clinical conference. We
also join in conferences several times a month withcardiac surgeons, obstetricians, pediatric surgeons andpediatric psychologists. In addition, each subspecialty
group has its own meeting and clinical round.
Many patients with significant disorders stay longin the hospital. We provide an official in-hospital
school ”Kodama Gakkyu” where patients receive
education and have chances to communicate with eachother and their parents in the hospital. “Niko-nikoVolunteer” members, an official volunteer group in thehospital, visit the pediatric ward every weekday toplay with the patients and help their mothers. It is agreat pleasure for both the patients and their mothers.
We also provide various activities for the patients in

the hospital such as the Tanabata festival, a Christmas
party and music concerts. All the residents, fellows
and nurses participate in these activities. We will havea child care specialist in the pediatric ward in April,2006.
(As of Dec 1, 2006)

Teaching activities
The staff members and the visiting lecturers givelectures of general pediatrics and pediatric diagnosis
for 36 hours to the second year students, and clinicalbedside learning in the inpatient ward for 2 weeks to
the third year students. During bedside learning for 2
weeks, specialized teaching sessions, like seminars areheld every day. In the outpatient learning, medical
students take histories and perform physical examinations of patients under the supervision of the teaching
staff. On the second and third days of the outpatient
clinic, each student visits the local pediatricians or
local hospitals in and around Tokyo. On the last day ofclinical learning, the Professor and an Associate Professor evaluate the students’ achievements. We havean elective clinical clerkship course for the third year
students.

Research activities
Our departments have the following researchgroups: nephrology, hematology/oncology, neurology,
cardiology, endocrinology, immunology, allergy, pulmonology and neonatology. We also have multidisciplinary research groups and laboratories such as cellbiology, genetic molecular biology and epidemiology.
The main subjects of research during the last year are
listed as follows.
1. Hematology/Oncology group: Using extremely
high grade oligonucleotide array system, many
deletions and amplifications in unreported genes
were identified in solid tumors including neuroblastoma, rhabdomyosarcoma and Ewing sarcoma.
2. Nephrology group: Genetic and clinical diversityof Dent disease was identified in more than 90
unrelated patients. In the field of podocyte biology,
novel mechanisms underlying the signal transduction via nephrin and neph1 was demonstrated.
3. Cardiology goup: A novel intervention cathether

172

technique in PDA was applied in several congenital heart disease patients.
4. Immunology group: A therapy using human dendritic cells for children’s cancer patients are performed.
5. Neonatology group: Clinical researches in theregulation of body fluid and circulation are being
conducted.

References
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Chen YY, Takita J, Mizuguchi M, Ida k, Koh K,
Igarashi T, Hanada R, Tanaka Y, Park M, Hayashi
Y: Mutation and expression analyses of the MET
and CDKN2A genes in rhabdomyosarcoma withemphasis on MET overexpression. Genes Chromosomes Cancer 16: 348-358, 2006.
Chen YY, Takita J, Hiwatari M, Igarashi T,
Hanada R, Kikuchi A, Hongo T, Taki T, Ogasawara M, Shimada A, Hayashi Y: Mutations of the
PTPN11 and RAS Genes in Rhabdomyosarcoma
and Pediatric Hematological Malignancies.
Genes Chromosomes Cancer 45: 583-591, 2006.
Inatomi J, Matsuoka K, Fujimaru R, Nakagawa A,
Iijima K: Mechanisms of development and progression of cyanotic nephropathy. Pediatr
Nephrol 21: 1440-1445, 2006
Kanamori Y, Tomonaga T, Sugiyama M, Hashizume K, Goishi K, Haga N: Bizarre presentationof epigastric heteropagus: report of a case. Surg
Today 36: 914-918, 2006
Kitanaka S, Sato U, Maruyama K, Igarashi T: A
compound heterozygous mutation in the BSND
gene detected in Bartter syndrome type IV. Pediatr Nephrol 21: 190-193, 2006
Kitanaka S, Takeda A, Sato U, Miki Y, Hishimura
A, Ieiri T, Igarashi T: A novel compound heterozygous mutation in the thyroglobulin gene
resulting in congenital goitrous hypothyroidismwith high serum triiodothyronine levels．J Hum
Gene 51: 379-382, 2006
Maeda E, Akahane M, Kato N, Hayashi N, Koga
H, Yamada H, Kato H, Ohtomo K: Assessment ofmajor aortopulmonary collateral arteries withmultidirector-row computed tomography Radiat
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Report of three cases and literature review. J
Child Neurol 21: 872-879, 2006
Park MJ, Shimada A, Asada H, Koike K, Tsuchida M, Hayashi Y: JAK2 mutation in a boy
with polycythemia vera, but not in other pediatrichematologic Disorders Leukemia. 20: 1453-1454,
2006
Nagayama J, Tomizawa D, Koh K, Nagatoshi Y,
Hotta N, Kishimoto T, Takahashi Y, Kuno T, Sugita K, Sato T, Kato K, Ogawa A, Nakahata T,
Mizutani S, Horibe K, Ishii E: Infants with acutelymphoblastic leukemia and a germline MLL
gene are highlycurable with use of chemotherapy
alone: results from the Japan Infant Leukemia
Study Group Blood. 107: 4663-4665, 2006
Okumura A, Kidokoro H, Mizuguchi M, Kurahashi H, Hirabayashi Y, Morishima T, Watanabe
K: The mildest form of acute necrotizing encephalopathy associated with influenza Neuropediatrics. 37: 261-263, 2006
Phan TG, Takanashi S, Kaneshi K, Ueda Y, Nakaya S, Nishimura S, Sugita K, Nishimura T,
Yamamoto A, Yagyu F, Okitsu S, Maneekarn N,
Ushijima H: Detection and genetic characterization of norovirus strains circulating among infants and children with acute gastroenteritis inJapan during 2004-2005. Clin Lab 52: 519-525,
2006
Saitoh M, Kubota M, Kimura I, Mizuguchi M,
Igarashi T: A case of panayiotopolos syndrome
showing an atypical course. Seizure 15: 643-648,
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Saito Y, Yamamoto T, Mizuguchi M, Kobayashi
M, Saito K, Ohno K, Osawa M: Altered glycosylation of alpha-dystroglycan in neurons of Fukuyama congenital muscular dystrophy brains.
Brain Res 1075: 223-228, 2006
Sekine T, Miyazaki H, Endou H: Molecularphysiology of renal organic anion transporters.
Am J Physiol Renal Physiol 290: 251-261, 2006
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173

17. Yamanouchi H, Kawaguchi N, Mori M, Imataka
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encephalopathy predominantly affecting thefrontal lobes (AIEF): A novel clinical category
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Epilepsy Res 70: 263-268, 2006
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174

Department of Pediatric surgery
Professor
Tadashi Iwanaka, M.D.,Ph.D.

Associate Professor
Yutaka Kanamori, M.D., Ph.D.

Research Associate
Masahiko Sugiyama, M.D.,

Makoto Komura, M.D., Ph.D.

Saori Nakahara, M.D., Ph.D.

Hiroshi Kawashima, M.D,

Homepage

http://square.umin.ac.jp/pedsurg/index.htm

History and organization
In 1951, a pediatric surgical team was established in
the Department of Second Surgery. Subsequently, in
1961, a pediatric surgical research team, which would
eventually research diaphragmatic hernia, was established with a chief, Dr. Ishida, by Professor Kimoto.
In 1971, it was authorized as the first clinical department of Pediatric Surgery in a National University.
A pediatric intensive care unit was founded with Prof.
Ishida in 1973, and a ward which could accommodate
mainly pediatric surgical patients was completed.
Assistant Prof. Saito assumed office as the first Director of this Pediatric Surgery clinical department.
Dr. Sumio Saito became Professor of Pediatric Surgery in 1983. Professor Saito had enthusiastically
performed clinical studies such as operation techniques and the use of biliary atresia.
Dr. Nakajo took office as a professor in 1985.
Prof. Nakajo had developed original operative procedures such as a radical operation for umbilical hernia
and an anti-reflex valve for biliary atresia. These
original operative procedures have been inherited bypediatric surgeons as Nakajo methods.
Our department was authorized as the Departmentof Pediatric Surgery in 1989 after Kyusyu University
by the Ministry of Education.
Dr. Yoshiaki Tsuchida assumed the role of Professor
in 1990 and published many highly regarded articles,

mainly concerning neuroblastoma and Wilm’s tumor
from research and clinical work.
In 1995, the department was reorganized as the Reproductive, Developmental and Aging Science, Pediatric Science and Pediatric Surgery, due to the University policy for the Graduate School.
In 1997, Dr Hashizume became Professor in the
Department of Pediatric Surgery. He started living-related partial liver transplantation (LRPLT) for
children with Professor Makuuchi in the Department
of Second Surgery.
Dr. Tadashi Iwanaka became the sixth Professor in
August 2006. The present staff are the chief professor,
one associate professor, four research associates, two
medical staff and three graduate students. More than
20 members of our department shoulder the clinicalwork as pediatric surgeons.

Clinical activities
Staff higher than research associate level takecharge of the out-patient clinic from Monday throughFriday. The pediatric surgical outpatient clinic takes
place in the same location as the pediatric outpatient
clinic and we closely cooperate with pediatricians todiagnose and treat patients. We also have specialized
outpatient clinics, liver and biliary tract clinics and atumor clinic. Recently, a second-opinion clinic has
opened with careful detailed explanations and this has

175

received a favorable reception.
Our ward is on the second floor south of the hospital A wing. Other pediatric surgical patients are also
admitted to this ward. We have 16 beds in the ward
and about 400 patients a year are hospitalized. Most
operation cases are inguinal hernia, but we have othercases such as respiratory surgery disease, neonatal
digestive organ obstructions, infant malignant tumors
such as Wilms' tumor and neuroblastoma, biliary tract
diseases such as biliary tract dilatation and biliaryatresia, trachea stenosis, and lung cysts.
We compare positively with Pediatric Surgery atother institutions that perform endoscopic surgery(laparoscopic surgery/thorascopic surgery). We havedeveloped an endoscopic surgery technique for pediatric diseases not covered by insurance to apply toadvanced medical care. Furthermore, we surgicallymanage seriously ill mentally and physically handicapped infants and nervous system intractable disease
patients to improve their quality of life, and we cooperate with pediatricians (neonatologists) to treat patients with prenatal diagnosis

Education
We expose 1st and 2nd year students to our dailyclinical work as well as research work during “Free
Quarter” and “Research Lab Visit” courses. Thesestudents are guided to be concerned with clinical areas
and are in charge of part of the research project. The
students hold a results announcement party at the endof training. For M2 students, general pediatric surgery
and neonatal surgery instruction is given by the professor and the lecturer.
An education program is also provided for M3 andM4 students for 5 days.
The bedside education of pediatric surgery consistsof participation in clinical conferences, attendance at
operations, and small group lectures concerning neonatal surgery, pediatric surgical oncology, pediatrichepatobiliary surgery, and pediatric emergency medicine which include the practice of cardiac massage
and intra-tracheal intubation using mannequins forpractice.
We take charge of the core surgical curriculum inthe “super-rotation” postgraduate training. We offer a
program in which each resident can learn basic

knowledge about pediatric surgical disease and surgery, and hemodynamic and respiratory evaluation as
well as basic surgical techniques and patient management.

Research activities
Professor Iwanaka started research on regenerative
medicine and founded a new laboratory in the Department of Tissue Engineering to perform not only
conventional animal experiments but also human experiments to fabricate a trachea in the clinical course.
In addition, he has established a low invasive operation study group and developed experiments for endscopic surgery using white rabbits in the animal resources research facilities. This study group tries todevelop endoscopic surgery for infants. Prof. Iwanaka
also provides a training program for infant endscopic
surgery for members of our department.
The continuing tumor study group analyzes thegenes related to tumor development. In addition, they
search for suppressor oncogenes in solid tumor neuroblastoma, Wilms' tumor, and Ewing's sarcoma. New
therapy using a virus is under development.
The hepato-biliary and transplantation group elucidated the immune system after liver transplantationand small intestinal transplantation. They also studied
the pathophysiology of clinical postoperative biliaryatresia.
The intestinal tract immunity study group was thefirst to start infant digestive organ function activation
medical treatment using a probiotic, Shinbiotic, withgood clinical effects, and also started a fundamental
study using an animal model.

References
1. Kanamori Y, Tomonaga T, Sugiyama M, Hashizume K, Goishi K, Haga N. Bizarre presentationof epigastric heteropagus: report of a case. Surg.
Today. 2006;36(10):914-8.
2. Miyake T, Tanaka Y, Kato K, Tanaka M, Sato Y,
Ijiri R, Inayama Y, Ito Y, Aoki S,
Kawabe R, Tohnai I. Gene mutation analysis andimmunohistochemical study of beta-catenin inodontogenic tumors. Pathol. Int. 2006 Dec;56(12):732-7.

176

3. Kuroda T, Saeki M, Honna T, Kumagai M, Masaki H. Late complications after surgery in patients with neuroblastoma. J. Pediatr. Surg. 2006
Dec;41(12):2037-40.
4. Kuroda T, Morikawa N, Kitano Y, Sago H, Hayashi S, Honna T, Saeki M. Clinicopathologic assessment of prenatally diagnosed lung diseases. J.
Pediatr. Surg. 2006 Dec;41(12):2028-31.
5. Kasahara M, Horikawa R, Tagawa M, Uemoto S,
Yokoyama S, Shibata Y, Kawano T, Kuroda T,
Honna T, Tanaka K, Saeki M. Current role of livertransplantation for methylmalonic acidemia: a review of the literature. Pediatr Transplant. 2006
Dec;10(8):943-7.
6. Hayashi S, Sago H, Kitano Y, Kuroda T, Honna T,
Nakamura T, Ito Y, Kitagawa M, Natori M. Fetal
pleuroamniotic shunting for bronchopulmonary
sequestration with hydrops.Ultrasound Obstet
Gynecol. 2006 Dec;28(7):963-7.
7. Kitano Y, Matsuoka K, Honna T, Kuroda T,
Morikawa N, Hayashi S, Sago H. Venous arterialization in extralobar pulmonary sequestration
associated with fetal hydrops.J. Pediatr. Surg.
2006 Mar;41(3):490-4.
8. Suzuki C, Takahashi M, Morimoto H, Izawa A,
Ise H, Fujishiro J, Murakami T, Ishiyama J, Nakada A, Nakayama J, Shimada K, Ikeda U, Kobayashi E.: Efficacy of mycophenolic acid combinedwith KRP-203, a novel immunomodulator, in a rat
heart transplantation model. J Heart Lung Transplant. 2006;25(3):302-9.
9. Fujishiro J, Suzuki C, Kudou S, Yasue T, Hakamata Y, Takahashi M, Murakami T, Hashizume K,
Kobayashi E: Change from Cyclosporine A to the
Combination Therapy of Mycophenolic Acid witha New Sphingosine-1-Phosphate Receptor Agonist,
KRP-203, Prevents Host Nephrotoxicity andTransplant Vasculopathy in Rats. J Heart Lung
Transplant. 2006; 25(7):825-33.
10. Fujishiro J, Kudou S, Iwai S, Takahashi M,
Hakamata Y, Kinoshita M, Iwanami S, Izawa S,
Yasue T, Murakami T, Hashizume K, Kobayashi
E: Use of sphingosine-1-phosphate 1 receptor
agonist, KRP-203, in combination with a subtherapeutic dose of cyclosporine A for rat renaltransplantation.
Transplantation 2006 Sep
27;82(6):804-12

178

Department of Geriatric Medicine
Department of Aging Research
Professor
Yasuyoshi Ouchi, M.D.,Ph.D.

Associate Professor
Masahiro Akishita, M.D., Ph.D.

Lecturer
Shinji Teramoto, M.D., Ph.D.,

Masato Eto, M.D., Ph.D.

Katsuya Iijima, M.D., Ph.D.

Associate
Sumito Ogawa, M.D., Ph.D.,

Yumiko Ohike, M.D., Ph.D.

Yasuhiro Yamaguchi, M.D., Ph.D.,

Hiroshi Yamamoto, M.D.

Homepage

http://www.m.u-tokyo.ac.jp/mcm/

Introduction and Organization

Clinical activities

The Department of Geriatrics was established in
1962, as the first geriatric department in Japan.
Since elderly patients usually have multiple organ
disorders, we have to take care the patients as a wholefrom multiple points of view. In addition, in the elderly patients, symptoms, signs and responses to thetreatment are sometimes quite different from theyoung. We have to have a broad knowledge on thephysiological and metabolic changes with aging when
we treat the elderly patients. Quality of life of the patients is another point of view which should be emphasized.
Our sub-specialty includes respirology, cardiology,
neurology, hematology, endocrinology, and bone metabolism, besides the general geriatric internal medicine.
We are trying to elucidate the pathophysiology of
aging process and understand elderly patients fromviewpoints of basic aging science using molecularbiology technique and clinical aspects using the recent
advancement of technology and geriatric assessment.

In the clinical ward, there are around 20 patients
who are taken care of by junior, senior and chief residents of our staff. Because senior and chief residents
are very experienced, they team up with a junior resident, give instructions as to the assessment of the patient's problem, making of future plans, and help theresident with various procedures. Very important issues are discussed and decisions are made in weekly
professor's round.
Specialized services are provided to out-patients ona daily basis in all areas of internal medicine. Approximately 300 new and a total of 16,000 patients
visit the out-patient clinic in a year.

Teaching activities
Clinical education is provided for fifth and sixthyear medical students on a man-to-man basis with afaculty staff member. During the period, the student
studies one or two cases, through which the student
learns the techniques interrogation and physical ex-

179amination, interpretation of laboratory tests, and actual medical procedures. Interpretation of the resultsof geriatric assessment is studied through lectures in acase-oriented manner with an emphasis placed on themultidisciplinary basis of geriatric patients.

Research activities
Pulmonary unit
Lung mechanics, exercise physiology, management
and assessment of dyspnea, sleep study for nocturnal
disturbed breathing, latent virus infection in airways,
animal model of aging lung, prediction and preventionof aspiration pneumonia, pathophysiology of interstitial lung disease, role of adhesion molecule in airway
disease, role of endothelin, leukotrienes, and neuropeptides in asthma, proliferation and differentiationof lung fibroblasts, proliferation and apoptosis of airway disease, defensin and infectious disease.
Cardiovascular unit
Research on the mechanism and regulation of vascular calcification, sex hormone regulation of vascularfunction, clinical evaluation of vascular function using
vascular ultrasound and pulse wave velocity, metabolic syndrome in the elderly.
Neurology unit
Diagnosis and treatment of the demented patients,
neuro-protective function of Thioredoxin in Drosophila, regulation of apoptosis by stress-responsive
kinases, etc
Osteoporosis and endocrinology unit
Bone metabolism, mechanism of action nuclear ofreceptors, genetic analysis of osteoporosis, vitamin K
action, hormone dependent cancer.

References
1. Yu W, Akishita M, Xi H, Nagai K, Sudoh N, Hasegawa H, Kozaki K, Toba K. Angiotensin converting enzyme inhibitor attenuates oxidative
stress-induced endothelial cell apoptosis via p38
MAP kinase inhibition. Clin Chim Acta. 364:328334, 2006.
2. Suzuki Y, Akishita M, Arai H, Teramoto S, Mori-

moto S, Toba K. Multiple consultations and polypharmacy of patients attending geriatric outpatient
units of university hospitals. Geriatr Gerontol Int
6:244-247, 2006
3. Oishi Y, Ozono R, Yoshizumi M, Akishita M,
Horiuchi M, Oshima T. AT2 receptor mediates the
cardioprotective effects of AT1 receptor antagonist in post-myocardial infarction remodeling.
Life Sci 80: 82-88, 2006
4. Glass CK, Ogawa S. Combinatorial roles of nuclear receptors in inflammation and immunity. Nat.
Rev. Immunol. 6:44-55, 2006
5. Eto M, Rathgeb L, Cosentino F, Kozai T, Luscher
TF. Statins blunt thrombin-induced downregulation of endothelial nitric oxide synthase expression in human endothelial cells. J Cardiovasc
Pharmacol. 47:663-667, 2006
6. Son BK, Kozaki K, Iijima K, Eto M, Kojima T,
Ota H, Senda Y, Maemura K, Nakano T, Akishita
M, Ouchi Y. Statins protect human aortic smoothmuscle cells from inorganic phosphate-induced
calcification by restoring Gas6-Axl survival
pathway. Circ Res 98: 1024-1031,2006
7. Teramoto S, Kume H, Ishii T, Yamamoto H, Yamaguchi Y, Ishii M, Hanaoka Y, Ouchi Y. Reference values for 6-min walk distance in Asian
adults may not be different from that of Caucasian
adults. Respirology. 11:669-670,2006
8. Arai H, Yamamoto A, Matsuzawa Y, Saito Y, Yamada N, Oikawa S, Mabuchi H, Teramoto T, Sasaki J, Nakaya N, Itakura H, Ishikawa Y, Ouchi Y,
Horibe H, Shirahashi N, Kita T. Prevalence of
metabolic syndrome in the general Japanese
population in 2000. J Atheroscler Thromb. 13:
202-208, 2006
9. Teramoto S, Kume H, Yamaguchi Y, Yamamoto H,
Ishii M, Ishii T, Ouchi Y. Heart rate variation
analysis may not effectively detect sleep apnoeas
in heart failure. Eur Respir J. 28:457-458, 2006
10. Kaneki M, Hosoi T, Ouchi Y, Orimo H. Pleiotropic actions of vitamin K: protector of bonehealth and beyond? Nutrition. 22:845-852, 2006
11. Shukuwa K, Izumi S, Hishikawa Y, Ejima K,
Inoue S, Muramatsu M, Ouchi Y, Kitaoka T, Koji
T. Diethylstilbestrol increases the density of
prolactin cells in male mouse pituitary by inducing proliferation of prolactin cells and transdif-

180ferentiation of gonadotropic cells. Histochem Cell
Biol. 126:111-123, 2006
12. Teramoto S, Ishii T, Yamamoto H, Yamaguchi Y,
Ouchi Y. Nasogastric tube feeding is a cause of
aspiration pneumonia in ventilated patients. Eur
Respir J. 27:436-437, 2006
13. Horie-Inoue K, Takayama K, Bono HU, Ouchi Y,
Okazaki Y, Inoue S. Identification of novel steroid
target genes through the combination of bioinformatics and functional analysis of hormone response elements. Biochem Biophys Res Commun.
339:99-106, 2006
14. Ota H, Tokunaga E, Chang K, Hikasa M, Iijima K,
Eto M, Kozaki K, Akishita M, Ouchi Y, Kaneki M.
Sirt1 inhibitor, Sirtinol, induces senescence-likegrowth arrest with attenuated Ras-MAPK signaling in human cancer cells. Oncogene. 25:176-185,
2006
15. Yu J, Eto M, Akishita M, Kaneko A, Ouchi Y,
Okabe T. Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in humanaortic endothelial cells: A possible involvement of
androgen receptor. Biochem Biophys Res Commun. 353:764-769, 2007
16. Son BK, Kozaki K, Iijima K, Eto M. Nakano T,
Akishita M, Ouchi Y. Gas6/Axl-PI3K/Akt pathway plays a central role in the effect of statins on
inorganic phosphate-induced calcification of vascular smooth muscle cells. Eur J Pharmacol.
556:1-8, 2007
17. Xi H, Akishita M, Nagai K, Yu W, Hasegawa H,
Eto M, Kozaki K, Toba K. Potent free radical
scavenger, edaravone, suppresses oxidative
stress-induced endothelial damage and early
atherosclerosis. Atherosclerosis 191:281-289,
2007
18. Yamamoto H, Nagase T, Shindo T, Teramoto S,
Aoki-Nagase T, Yamaguchi Y, Hanaoka Y, Kurihara H, Ouchi Y. Adrenomedullin insufficiency
increases allergen induced airway hyperresponsiveness in mice. J Appl Physiol. 102:2361-2368,
2007
19. Teramoto S, Yamamoto H, Yamaguchi Y, Hanaoka
Y, Ishii M, Hibi S, Ouchi Y. ACE inhibitors prevent aspiration pneumonia in Asian, but not Caucasian, elderly patients with stroke. Eur Respir J.
29:218-219, 2007

20. Teramoto S, Kume H, Yamaguchi Y, Yamamoto H,
Hanaoka Y, Ishii M, Ishii T, Ouchi Y. Improvement of endothelial function with allopurinol may
occur in selected patients with OSA: effect of age
and sex. Eur Respir J. 29:216-217, 2007
21. Kano MR, Bae Y, Iwata C, Morishita Y, Yashiro
M, Oka M, Fujii T, Komuro A, Kiyono K,
Kaminishi M, Hirakawa K, Ouchi Y, Nishiyama N,
Kataoka K, Miyazono K. Improvement of cancer-targeting therapy, using nanocarriers for intractable solid tumors by inhibition of TGF-beta
signaling. Proc Natl Acad Sci U S A. 104:34603465, 2007
22. Kinoshita H, Nakagawa K, Narusawa K, Goseki-Sone M, Fukushi-Irie M, Mizoi L, Yoshida H,
Okano T, Nakamura T, Suzuki T, Inoue S, Orimo
H, Ouchi Y, Hosoi T. A functional single nucleotide polymorphism in the vitamin-K-dependent
gamma-glutamyl carboxylase gene (Arg325Gln)
is associated with bone mineral density in elderly
Japanese women. Bone. 40:451-456, 2007
23. Fujimura T, Takahashi S, Urano T, Kumagai J,
Ogushi T, Horie-Inoue K, Ouchi Y, Kitamura T,
Muramatsu M, Inoue S. Increased expression of
estrogen-related receptor alpha (ERRalpha) is anegative prognostic predictor in human prostatecancer. Int J Cancer. 120:2325-2330, 2007
24. Urano T, Shiraki M, Narusawa K, Usui T, Sasaki
N, Hosoi T, Ouchi Y, Nakamura T, Inoue S. Q89R
polymorphism in the LDL receptor-related protein
5 gene is associated with spinal osteoarthritis in
postmenopausal Japanese women. Spine. 32:2529, 2007
25. Teramoto S, Kume H, Yamaguchi Y, Yamamoto H,
Hanaoka Y, Ishii M, Ishii T, Ouchi Y. Improvement of endothelial function with allopurinol may
occur in selected patients with OSA: effect of age
and sex. Eur Respir J. 29:216-217, 2007
26. Kojima T, Ako J, Eto M, Iijima K, Akishita M,
Ouchi Y. Tako-tsubo-like left ventricular dysfunction in a patient with chronic total occlusion of theleft anterior descending artery. Int J Cardiol. 119:e19-21, 2007
27. Ghisletti, S., Huang, W., Ogawa, S., Pascual, G.,
Lin, M., Willson, TM., Rosenfeld, MG., and Glass,
C.K. Parallel SUMOylation-dependent pathways
mediate gene- and signal-specific transrepression

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by LXRs and PPARγ. Mol. Cell 25:57-70, 2007
28. Akishita M, Hashimoto M, Ohike Y, Ogawa S,
Iijima K, Eto M, Ouchi Y. Low testosterone levelis an independent determinant of endothelial dysfunction in men. Hypertens Res. (in press)
29. Takayama K, Kaneshiro K, Tsutsumi S,
Horie-Inoue K, Ikeda K, Urano T, Ijichi N, Ouchi
Y, Shirahige K, Aburatani H, Inoue S. Identification of novel androgen response genes in prostatecancer cells by coupling chromatin immunoprecipitation and genomic microarray analysis. Oncogene. (in press)
30. Yamamoto H, Teramoto S, Yamaguchi Y, Hanaoka
Y, Ishii M, Hibi S, Ouchi Y . Long-term oxygen
administration reduces plasma adrenomedullin
levels in patients with obstructive sleep apnea
syndrome. Sleep Med. (in press)
31. Yamaguchi Y, Nagase T, Tomita T, Nakamura K,
Fukuhara S, Amano T, Yamamoto H, Ide Y, Suzuki M, Teramoto S, Asano T, Kangawa K, Nakagata N, Ouchi Y, Kurihara H. {beta}-defensin
overexpression induces progressive muscle degeneration in mice. Am J Physiol Cell Physiol. (inpress)

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Thoracic Surgery
Professor
Takamoto, Shinichi

Associate Professor
Nakajima, Jun

StaffsMurakawa, Tomohiro and Fukami, Takeshi

Homepage

http://ctstokyo.umin.ne.jp/

History
Clinical and basic researches of the thoracic surgery
has been performed since the prewar era in this university, when Professor Masao Tsuduki adopted themodified Coryllos’s thoracoplasty for the treatment of
the pulmonary tuberculosis in 1934. They initiatedthoracoscopy for the treatment of the tuberculosis in
our country. After the successful application of theantituberculous drugs, surgical treatment of the thoracic malignant neoplasms was the major concern of
the thoracic surgery.
The Department of Cardiothoracic Surgery, The
University of Tokyo, was established in December 15,
1964 as the first department of this field along withthe cardiovascular surgery in the Japanese national
universities. Since then it has played an internationallyleading role and contributed to development of the
field in our country.
Professors and Chairs in the history of the department are as follows: Kimoto, Seiji (1964.12.15 ~1968.3.31), Saigusa, Masahiro (1968.4.1 ~ 1981.3.31),
Asano, Ken-ichi (1981.4.1 ~ 1986.3.31), Furuse,
Akira (1986.4.1 ~ 1997.3.31) and Takamoto, Shinichi(1997.6.1 ~).
The Department of Cardiothoracic Surgery has been
divided into two departments, Department of Cardiovascular Surgery and Department of Thoracic Surgery
in 1998.
The mission of the Department of Thoracic Surgery
is to improve the patients with diseases of the thoracic

organs through clinical works, basic and clinical researches, and education of the medical students, postgraduates, and the surgical residents in our university.

Clinical activities
Three staffs (Nakajima J, Murakawa T, and FukamiT), certificated as members of the Japanese Board ofGeneral Thoracic Surgery, are in charge of the Department of Thoracic Surgery, University of Tokyo
Hospital. They specialize in surgical treatment of thediseases of the respiratory and the mediastinal organs
and the chest wall, except for diseases of the esophagus and mammary glands. Approximately 200 surgeries are performed annually in the department.
Primary lung cancer has been the leading cause ofdeath among the malignant neoplasms in our country.
As the number of the dead patients by the lung cancer
has been increasing, the basic and the clinical investigations for the treatment of the lung cancer are very
important. In our department, the staffs participate theclinical works, studies and educations of diagnostics
and therapeutics of the lung cancer as well as other
thoracic diseases.
We have performed the modern-style thoracoscopy
for the diagnosis and treatment of the thoracic disease
with less surgical invasiveness since 1992. Approximately a half of the surgical procedures in our department have been safely and successfully accomplished through thoracoscopy. Researches on
less-invasiveness, oncological advantage of the tho-185

racoscopic surgery have been studied actively.
Pulmonary metastasis represents far advanced malignant neoplasms of extrathoracic organs. Pulmonary
resection is an option for the treatment of pulmonary
metastasis. We actively perform pulmonary resection
through thoracoscopy on patients with pulmonary
metastasis who are eligible for surgical therapy.
Thymic epithelial neoplasms, such as thymoma andthymic carcinoma, show broad spectrum in the degreeof malignancy. They also associated with paraneoplastic syndromes, such as the myasthenia gravis andthe pure red cell aplasia. We have sought to establish
the strategies on diagnosis and treatment of these diseases, which are still yet to be determined, from ourclinical experiences of more than 200 cases with thediseases in our department.

Academic education
Medical students in the fifth grade have two-weeks’program on the clinical training of the thoracic and the
cardiovascular surgery. They are also able to participate the clinical clerkship of the cardiothoracic surgery, an elective course for 4 weeks. The Departmentof Thoracic Surgery also offers the 4-year postgraduate program for qualified surgeons who are willing to
specialize in the thoracic surgery.

Current researches
Main subjects of current research at present include
basic and clinical studies on the malignant neoplasmsin the thorax, transplantation of the thoracic organs
and the cryopreserved tissues. Recently we conductedclinical studies on the immunotherapy with adopted
gamma- delta- T-cell for the treatment of the advanced
non-small cell lung cancer.
The following are the major themes under research:(1) New oncogenes or suppressor oncogenes of thelung cancer(2) New methods for quantitative analysis of the
DNA methylation of the lung cancer.
(3) Clinical studies on the less-invasive surgicaltreatment of the thoracic malignancies(4) Analysis of the factors influencing the prognosisof lung cancer or mediastinal neoplasms is also
performed.

(5) Adoptive anticancer immunity of the autologous
gamma-delta-T-cell(6) Mechanisms of acute or chronic rejection of theallogeneic trachea.

Selected publications
1. Goto A. Nakajima J. Hara K. Niki T. Fukayama M.
Lung adenocarcinoma associated with familial adenomatous polyposis. Clear cell carcinoma withbeta-catenin accumulation accompanied by atypicaladenomatous hyperplasia. Virchows Archiv. 446 :
73-77, 2005
2. Takeuchi E, Murakawa T, Tanaka M, Naka-jima J,
Takamoto S. Coccidioidomycosis of the lung contracted abroad. Jpn J Thorac Car-diovasc Surg. 53:
173-175, 2005.
3. Nakajima J, Matsumoto J, Takeuchi E, Fu-kami T,
Takamoto S. Rearrangement of T-cell receptor beta
and gamma genes in thymoma. Asian Cardiovasc
Thorac Ann. 13: 149-152, 2005.
4. Nakajima J, Tanaka M, Matsumoto J, Ta-keuchi E,
Fukami T, Takamoto S. Appraisal of surgical treatment for pulmonary metas-tasis from hepatocellular
carcinoma. World J Surg. 29: 715-718, 2005
5. Akamatsu N, Sugawara Y, Nakajima J, Ki-shi Y,
Niiya T, Kaneko J, Makuuchi M. Re-section of apulmonary lesion after liver transplantation: reportof a case. Surg Today. 35: 976-978, 2005
6. Akamatsu N, Sugawara Y, Nakajima J, Ki-shi Y,
Kanekio J, Makuuchi M. Cryptococco-sis after living donor liver transplantation: report of three cases.
Transplant Infectious Disease 7: 26-29, 2005
7. Nakajima J, Sato H, Takamoto S. Does pre-operativetransbronchial biopsy worsen the postsurgical prognosis of lung cancer? A propensity score-adjusted
analysis. Chest. 128: 3512-3518, 2005
8. Murakawa T, Kerklo MM, Zamora MR, Wei Y, Gill
RG, Henson PM, Grover FL, Nicolls MR. Simultaneous LFA-1 and CD40 ligand an-tagonism prevents
airway remodeling in or-thotopic airway transplantation: implica-tions for the role of respiratory epithelium as a modulator of fibrosis. J Immunol. 174:3869-3879, 2005
9. Mori N, Hitomi S, Nakajima J, Okuzumi K, Murakami A, Kimura S. Unselective use of intranasal
mupirocin ointment for control-ling propagation of

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methicillin-resistant Staphylococcus aureus in athoracic surgery ward. J Infect Chemotherpy 11:231-233, 2005
10. Kammori M. Fukami T. Ogawa T. Tsuji E. Takubo
K. Nakajima J. Kaminishi M. Image in endocrinology: giant mediastinal cystic parathyroid adenoma.
Journal of Clinical Endocrinology & Metabolism.
91:1635-1636, 2006
11. Matsumoto J. Nakajima J. Takeuchi E. Fu-kami T.
Nawata K. Takamoto S. Successful perioperative
management of a middle mediastinal paraganglioma.
Journal of Thoracic & Cardiovascular Surgery. 132:705-706, 2006
12. Nakajima J, Takamoto S, Takeuchi E, Fukami T,
Sano A. Thoracoscopic surgery for pulmonary arteriovenous malformation. Asian Cardiovascular andThoracic Annals 14:412-415, 2006
13. Nakajima J, Takamoto S, Murakawa T, Fukami T,
Sano A. Interstitial pneumonia caused by collagendiseases: A contraindication for lung cancer surgery?
Surgery Today 37: 14-18, 2007
14. Nakajima J, Goto A, Takamoto S, Murakawa T, Fukami T, Kusakabe M. Invasive lymphangioma of thelung presented as a large pulmonary mass andhemoptysis. Surg To-day 37: 418-422, 2007
15. Nakajima J, Morota T, Matsumoto J, Takazawa Y,
Murakawa T, Fukami T, Yamamoto T, Takamoto S.
Pulmonary intimal sarcoma treated by a left pneumonectomy with pulmonary arterioplasty under cardiopulmonary bypass: Report of a Case. Surg Today
37: 496-499, 2007
16. Wang T. Niki T. Goto A. Ota S. Morikawa T. Nakamura Y. Ohara E. Ishikawa S. Aburatani H. Nakajima J. Fukayama M. Hypoxia increases the motilityof lung adenocarcinoma cell line A549 via activationof the epidermal growth factor receptor pathway.
Cancer Science. 98:506-511, 2007

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Department of
Cardiothoracic Surgery
Professor
Shinichi Takamoto, M.D.

Associate Professor
Arata Murakami, M.D.

Lecturer
Noboru Motomura, M.D.,

Tetsuro Morota, M.D.,

Minoru Ono, M.D.

Associate
Koh Takeuchi, M.D.,
Yoshio Doi, M.D.
Mitsuhiro Kawata, MD

Homepage

Tetsufumi Yamamoto, M.D.,
Aya Saito, MD

http://ctstokyo.umin.ne.jp/

Introduction and Organization
Cardiac surgery in the Department was initiated by
Dr. Seiji Kimoto, who performed ligation of patentductus arteriosus in June, aortic arch aneurysm resection in July and first-in-Japan Blalock-Taussig operation for Tetralogy of Fallot in October in 1951. Healso started implantation of alcohol-preserved aortic
homograft for abdominal aortic aneurysm in 1952, andclosed commissurotomy for mitral valve stenosis in
1954. The first open heart surgery (atrial septal defectclosure) was performed in 1955, using selective brain
perfusion cooling method that was developed in the
Department.
Establishment of Department of Thoracic Surgery
in the University of Tokyo Hospital was approved by
the government first in Japan December 15, 1964.
Under the leadership of Professor Kimoto excellent
research works were created especially on pacemakerand artificial heart, and many opinion leaders were
produced. Dr. Masahiro Saigusa, the second Professor,
endeavored to make open heart surgery safer by in-troducing new- generation heart-lung machines to the
Department. Dr. Kenichi Asano, the third Professor,
started posterior-leaflet preserving mitral valve replacement first in Japan. He also dramatically improved surgical results of Tetralogy of Fallot. Dr.
Akira Furuse, the fourth Professor, modernized management of extremely busy clinical works. During thistime, the Department was divided into two Divisions,
Cardiovascular and General thoracic, due to the University policy of Graduate-school.
Dr. Shinichi Takamoto assumed the fifth Professor
in June 1997. He rearranged clinical teams into threegroups (adult cardiac disease, thoracic aortic diseaseand congenital heart disease) to adapt the rapid progress of cardiovascular surgery. Present staffs are one
Chief Professor, one Associate Professor and three
Lecturer and five Associates.

Clinical Activities
Clinical conference starts at 7:15 am in weekdays.
Regular surgery is scheduled on Monday, Wednesday

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and Friday. Patient round is on Tuesday and Thursday.
Adult patients are hospitalized in the South Wing of
5th floor, and pediatric patients in the South Wing of
2nd floor. Clinics are open Monday through Friday forthe follow-up visit as well as for patient referral.
Case volume in recent years has been about 300,
which is one of the highest in Japan. We are leading inJapan by showing excellent surgical results. There areeight Board- certified surgeons, each of whom has his
own subspecialty among adult cardiac, thoracic aortic
or congenital heart disease. We are famous for aortic
valve sparing root replacement, arch replacement using retrograde cerebral perfusion, treatment of extended thoracic aortic aneurysm, ventricular assist
device implantation, off- pump coronary artery bypass
surgery, mitral valve plasty and repair of complex
congenital heart diseases, such as Jatene, Fontan and
Norwood operations.
The University of Tokyo Tissue Bank was founded
in 1997, based on the Department of Cardiovascular
Surgery. The Bank has been actively promoting procurement, preservation and shipping of human valve
and blood vessel allograft in Japan. We take the leadin surgical treatment using allograft for severe active
endocarditis or infection of aortic aneurysm or vascular prosthesis. Surgical treatment using allograft wasapproved as advanced medical technology by theGovernment in 2006. The first heart transplantation
was performed in May 2006 in The University Hospital.

Teaching Activities
We have the chair of systematic review of cardiovascular surgery in the spring term at the 2nd grade of
medical course. We also take charge in clinical practice on diagnosis of cardiovascular disease in the autumn term at the 2nd grade. We expose the students todaily clinical works as well as research works during
the course of “Free Quarter” and “Research Lab Visit”,
which are scheduled in the summer and spring vacations at 1st and 2nd grade. Joint lectures with the Cardiology Department are scheduled 3rd through 4th
grades. Each student is assigned one or two cardiovascular surgical cases in the Bed Side Learning, inwhich he/she is required to learn preoperative patient
evaluation and management, surgical treatment andpostoperative care, based on participatory practice.
There are also twelve small key-lectures on cardiovascular surgery. Hands-on practice is provided during
the “Clinical clerkship” one-month course in the lastmonths of 3rd grade.
We take charge in core surgical curriculum in the“Super-rotation” postgraduate training. We offer a
program in which each resident can learn basic
knowledge of cardiovascular disease and surgery, andhemodynamic and respiratory evaluation as well asbasic surgical techniques and patient management.
Residents who take the course of cardiovascular surgery are required four-year general surgical training.
We have well-developed specialty/ subspecialty training programs to allow the residents to pass Cardiovascular Board Examination by 10th postgraduate year.

Research Activities
In order to achieve excellent clinical results and toseek for new possibilities of surgical treatments, it isessential for cardiothoracic surgical department of the
University to have active research programs in clinicaland basic subjects. The cardiothoracic department of
the University of Tokyo has created highly active research programs in the every field of cardiothoracic
surgery, played an internationally leading role andcontributed to its development. A research meeting isheld every Saturday on a research project for every
member of the department to understand and to makefree thorough discussions of the subject.
Basic and/or clinical research activities are focusedon 1) new effective brain and spinal protection strategy, 2) intracardiac repair technique on a beating heart
guided by three-dimensional echo, 3) basic and clinical research on cryopreserved allograft, 4) treatmentof end-stage heart failure by ventricular assist device,5) a new technique of aortic valve sparing root replacement and its hemodynamic evaluation, 6) development of intrauterine treatment for fetal heart disease,7) postoperative adhesion-proof membrane, 8) treatment of acute and chronic rejection after heart transplantation.

References
1. Taketani T, Nawata K, Motomura N, Ono M, Ta-

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kamoto S: Acute stenosis of porcine stentless bioprosthesis caused by infective endocarditis. Circulation 114:e567-568, 2006
2. Morota T. Takamoto S. Kitamura T. Motomura N.
Ono M: Clinical experience with Cryopreserved
Allografts for Aortic Infection. J Jpn Coll Angiol
46:817-822, 2006
3. Takeuchi K. McGowan FX Jr. Bacha EA. MayerJE Jr. Zurakowski D. Otaki M. del Nido PJ:
Analysis of surgical outcome in complex double-outlet right ventricle with heterotaxy syndrome or complete atrioventricular canal defect.
Ann Thorac Surg 82:146-152, 2006
4. Takeuchi K. Murakami A. Takaoka T. Takamoto
S: Evaluation of valved saphenous vein homograftas right ventricle-pulmonary artery conduit inmodified stage I Norwood operation. Interact CardioVasc Thorac Surg 5:345-348, 2006
5. Takeuchi K. Murakami A. Hirata Y. Kitahori K.
Doi Y. Takamoto S: Surgical Outcome of Heterotaxy Syndrome in a Single Institution Asian. Cardiovasc Thorac Ann 14:489-494, 2006
6. Hisagi M. Higuchi K. Koseni K. Inaba H: Total
Anomalous Pulmonary Venous Return in an Adult.
Asian Cardiovasc Thorac Ann 14:e27-29, 2006
7. Ohno T, Ando J, Ono M, Morita T, Motomura N,
Hirata Y, Takamoto S: The Beneficial effect ofcoronary-artery-bypass surgery on survival in patients with diabetic retinopathy. Eur J Cardiothorac Surg 30:881-886, 2006
8. Ono T, Ohashi T, Asakura T, Ono N, Ono M,
Motomura N, Takamoto S: Impact of diabetic
retinopathy on cardiac outcome after coronary artery bypass graft surgery: prospective observational study. Ann Thorac Surg 81:608-612, 2006
9. Tsukihara H. Takamoto S. Kitahori K. Matsuda K.
Murakami A. Novick RJ. Suematsu Y: Preventionof Postoperative Pericardial Adhesions With a
Novel Regenerative Collagen Sheet. Ann Thorac
Surg 81:650-657, 2006
10. Kawata M, Sekino M, Takamoto S, Ueno S, Yamaguchi S, Kitahori K, Tsukihara H, Suematsu Y,
Ono M, Motomura N, Morota T, Murakami A:
Retrograde cerebral perfusion with intermittent
pressure augmentation provides adequate neuroprotection: diffusion- and perfusion-weighted

magnetic resonance imaging study in an experimental canine mode. J Thorac Cardiovasc Surg
132:933-940, 2006
11. Kawata M, Takamoto S, Kitahori K, Tsukihara H,
Morota T, Ono M, Motomura N, Murakami A,
Suematsu Y: Intermittent pressure augmentation
during retrograde cerebral perfusion under moderate hypothermia provides adequate neuroprotection: an experimental study. J Thorac Cardiovasc
Surg 132:80-88, 2006
12. Kawata M, Takamoto S, Kitahori K, Tsukihara H,
Morota T, Ono M, Motomura N, Murakami A,
Suematsu Y: Erythropoietin protects the central
nervous system during prolonged hypothermic
circulatory arrest: an experimental study in a canine model. J Thorac Cardiovasc Surg 131:13311337, 2006
13. Kawata M., Atsumi N., Nakayama S: Poor response to a balloon atrial septostomy in TGA withpulmonary hypertension. Chirurgia 19:169, 2006
14. Kawata M., Atsumi N., Nakayama S: Acuteprolapse of floppy mitral valve in an infant. Chirurgia 19:41, 2006
15. Higuchi K. Koseni K. Takamoto S.: Graft insertion technique for distal anastomosis in cases ofascending aortic aneurysm. J Cardiovasc Surg 46:
537-8, 2005
16. Kubota H. Takamoto S. Furuse A. Sato M. Endo
H. Fujiki T. Sudo K.: Epicardial maze procedureon the beating heart with an infrared coagulator.
Ann Thorac Surg 80:1081-6, 2005
17. Kawata M. Takamoto S. Morota T. Ono M.
Motomura N. Murakami A. Suematsu Y.: Is theguideline the cause of structural failure in current
polyester vascular prostheses? An experimental
study. Artif Organs. 29:820-5, 2005
18. Yamamoto T. Sata M. Fukuda D. Takamoto S.:
The angiotensin II type 1 receptor blocker valsartan attenuates graft vasculopathy. Basic Res Cardiol 100:84-91, 2005
19. Miyaji K. Murakami A. Takasaki T. Ohara K.
Takamoto S. Yoshimura H.: Does a bidirec- tional
Glenn shunt improve the oxygenation of rightventricle-dependent coronary circulation in pulmonary atresia with intact ventricular septum? J
Thorac Cardiovasc Surg 130:1050-3, 2005

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20. Kawata M. Morota T. Takamoto S. Kubota H.
Kitahori K.: Non-anastomotic rupture in theguideline of a Dacron thoracic aortic graft. J Vasc
Surg 42:573, 2005
21. Takamoto S.: Managing surgical quality based on
database. Jap J Thorac Cardiovasc Surge 53:337,
2005
22. Kitahori K. Takamoto S. Takayama H. Suematsu
Y. Ono M. Motomura N. Morota T. Takeuchi K.:
A novel protocol of retrograde cerebral perfusion
with intermittent pressure augmentation for brain
protection. J Thorac Cardiovasc Surg 130:363-70,
2005
23. Tanaka K. Sata M. Fukuda D. Suematsu Y.
Motomura N. Takamoto S. Hirata Y. Nagai R.:
Age-associated aortic stenosis in apolipoprotein
E-deficient mice. J Am Coll Cardiol 46:134-41,
2005
24. Miyairi T. Takamoto S. Kotsuka Y. Takeuchi A.
Yamanaka K. Sato H.: Comparison of neuroncognitive results after coronary artery bypass grafting
and thoracic aortic surgery using retrograde cerebral perfusion. Eur J Cardio- Thorac Surg 28:97101; 2005
25. Omoto R. Kyo S. Nishimura M. Matsuda H.
Matsumiya G. Kitamura S. Nakatani T. Takamoto
S. Ono M. Tabayashi K. Yozu R.: Japanese multicenter clinical evaluation of the HeartMate
vented electric left ventricular assist system. J
Artif Organs. 8:34-40, 2005
26. Kitamura T. Morota T. Motomura N. Ono M.
Shibata K. Ueno K. Kotsuka Y. Takamoto S.:
Management of infected grafts and aneurysms of
the aorta. Ann Vasc Surg 19:335-42, 2005
27. Kitamura T. Sata M. Motomura N. Takamoto S.:
Seeding of recipient bone marrow cells reduces
neointimal hyperplasia of deendo- thelialized rat
aortic allograft. Int Heart J 46:303-12, 2005
28. Taketani T. Imai Y. Morota T. Maemura K.
Morita H. Hayashi D. Yamazaki T. Nagai R.
Takamoto S.: Altered patterns of gene expression
specific to thoracic aortic aneurysms: microarray
analysis of surgically resected specimens. Int
Heart J 46:265-77, 2005
29. Taketani T. Miyata T. Morota T. Takamoto S.
Surgical treatment of atypical aortic coarctation

complicating Takayasu's arteritis--experience with
33 cases over 44 years. J Vasc Surg 41:597-601,
2005
30. Hashimoto T. Sugawara Y. Kishi Y. Akamatsu N.
Matsui Y. Kokudo N. Motomura N. Takamoto S.
Makuuchi M.: Superior vena cava graft for right
liver and right lateral sector transplantation.
Transplantation. 79:920-5, 2005
31. Hirata Y. Sata M. Motomura N. Takanashi M.
Suematsu Y. Ono M. Takamoto S.: Human umbilical cord blood cells improve cardiac function
after myocardial infarction. Biochem Bioph Res
Com 327:609-14, 2005
32. Taketani T. Motomura N. Toyokawa S. Kotsuka
Y. Takamoto S.: Beneficial effect of acute normovolemic hemodilution in cardio- vascular surgery. Jap J Thorac Cardiovasc Surg 53:16-21,
2005

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Department of
Gastrointestinal Surgery
Professor
Michio Kaminishi MD. PhD.

Lecturer
Sachiyo Nomura MD. PhD.

Associates
Hirokazu Yamaguchi MD,
Ikuo Wada MD. PhD.,
Akemi Yoshikawa MD. PhD.,
Kouji Nozaki MD. PhD.,
Kazuhiko Mori MD. PhD.,

Nobuyuki Shimizu MD.PhD,
Kzuhiko Yamada MD. PhD.,
Tetsuya Ueda MD. PhD.,
Fumihikko Hatao MD. PhD.,
Youko Matsui MD. PhD.

Homepage
General Affairs:
Since 2001, the former Third Department of Surgery, which was located in a branch hospital of the
University of Tokyo, has been divided into two departments, the Department of Gastrointestinal Surgery
and the Department of Metabolic Care and Endocrine
Surgery, in line with the integration of the main andbranch hospitals the elevation to a department in thegraduate school of medicine at our university. Our
research activities in both departments have been wellorganized and ultimately successful by maintaining aclose connection. The Department of Gastrointestinal
Surgery presently comprises one Professor, one Lecturer，one Hospital Lecturer and nine associates.
With the prolongation of life expectancy, there are
increasing numbers of multi-morbid patients requiring
multi-organ treatment, as well as a greater need for
multidisciplinary approaches to the patients. Our
clinical and research activities have for the most partreceived the cooperation of members in the Department of Metabolic Care and Endocrine Surgery as
well as those in other surgical departments at the
University of Tokyo.

Our fundamental principles of patient treatment arecomprehensive patient care which includes pre-, peri-,and postoperative management of the diseases as wellas patient care over long-term postoperative periods
which often extend to the terminal stage. We believethat patient care encompassing the entire lifespan provides a wealth of valuable information concerning theappropriateness of current treatment strategy, the establishment of new surgical designs, the developmentof new basic research activities which can much contribute to clinical fields, and indications of desirable
modes of terminal care.
Fostering good surgeons as well as scientists whomeet both clinical and academic needs has always
been the guiding principle of our Department.

Educational Activities:
We educate chief residents and junior residents inrotation．Our educational systems for residents andstudents reflect our aforementioned principles. Medical students are encouraged to be members of clinicalstaffs rather than mere students during their bedside
Learning. They learn generic patient care which

192

encompasses not only perioperative management ofdiseases but also non-surgical management of postoperative disorders and terminal care. Our educational
system provides medical students with a great deal ofpractical information from the medical point of view
as well as better opportunities to ponder the implications of life and death.
Junior residents rotate every three months. Aftercompletion of their initial training program, they go
into a further clinical training program for several
consecutive years and become a chief resident. We
have also several postgraduate students who aremainly engaged in research work. Their researchworks are under supervision of the Professor.

Research Activities:
The main research activities of the department of
Gastrointestinal Surgery are focused on diagnosis andtherapy for gastrointestinal diseases and clinical andbasic research for gastrointestinal carcinogenesis
from the view point of “Surgery and Inflammation”.
The department's research activities have focused on awide spectrum of research topics, ranging from basic
research topics to clinical ones. Our research activities
have been well organized and ultimately achieved bymaintaining a close connection between hospital andlaboratory activities. Our medical staffs make every
effort to promote the research activities and obtain
successful results. Current research topics are:1) Carcinogenesis of gastrointestinal cancer- Diversity of gastointestinal carcinogenesis-Gender differences in gastrointestinal cancers- Roles of sex hormones in gastrointetinal carcinogenesis- Monoclonality of intestinal metaplasia- Roles of Helicobactor pylori infection in gastriccarcinogenesis- Interaction between cancer and interstitial tissue- Experimental evaluation of promotive mechanisms of gastroduodenal reflux and denervationof the gastric mucosa in gastric remnant carcinogenesis- Preventative roles of PPARr in gastric carcinogenesis- Clinical and experimental studies on the Barrett

esophagus
2) Molecular mechanisms of gastrointestinal tract
cancer- Role of bone marrow derived progenitor cells ingastric carcinogenesis- Apoptosis-related molecules during multimodal
therapies for esophageal cancer- Angiogenic factors in gastrointestinal tract cancer- Genetic alterations in gastric cancer and colorectal cancer- Methylation status of gastrointestinal cancers- Lymph node micrometastasis of gastric cancer
3) Minimally invasive surgery for the treatment ofearly cancer of the stomach and large intestine- Endoscopic treatment- Laparoscopic surgery- Optimal scope of lymphadenectomy- Sentinel lymph node navigation surgery forearly gastric cancer- Evaluation of postoperative QOL after pylorus
preserving gastrectomy (PPG) and jejunal interposition for early gastric cancer4) Alternative surgical design for the improvementof the patient's postoperative quality of life5) Radical treatment for advanced gastric cancer6) Multimodal treatment for gastrointestinal tract
cancer- Neoadjuvant or definitive chemoradiation therapy for esophageal cancer- Neoadjuvant or adjuvant chemotherapy for gastric and colorectal cancer7) Gastrointestinal motility- Mechanism of pepermint oil solution of digestive tract- Role of cytokine and COX-2 in gastrointestinal
motility- Manipulation of the intestine and postoperative
motility

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Clinical Activities:
We have outpatient clinics from Monday throughFriday. We have specialized divisions for outpatientmanagement of esophageal, gastric, and colorectal
diseases. The ward is divided into four subgroups, andeach of them has one medical staff for supervision,
one assistant supervisor, one chief resident, and one or
two junior residents in rotation. They are on duty fordaily patient care under the supervision of medical
staffs. Ordinary, each subgroup takes care of 10-12
patients.
We have our own multidisciplinary disease evaluation systems for inpatients and outpatients, such as
endoscopy and endoscopic ultrasonography for upperand lower gastrointestinal tracts, ultrasound diagnosis,
and barium roentgenogram. These multidisciplinary
services provide good opportunities to evaluate thediseases systematically from the surgeon's standpoint.
We also perform endoscopic treatment, especiallymucosal resection for strictly selected early cancers in
the upper and lower gastrointestinal tract.
The weekly official activities of our department are
Ward Rounds by the Professor on Monday and by the
Associate Professor on Friday. We have post- andpreoperative case conferences on Tuesday, Wednesday
and Thursday morning, respectively, and a journal
club on Monday. We also have a specialized uppergastrointestinal case conference on Tuesday evening.
Nursing-staffs have meetings with medical doctors on
every Friday to ensure a high quality of patient careduring the patients' hospital stay.
Generally, elective surgery is scheduled on Tuesday，
Wednesday and Thursday. The statistics for 20 ５
show more than 250 cases of elective surgery andemergency surgery. All residents and medical personnel work many extra hours with high motivation
whenever it is necessary for the good of the patients.

References (2002 - March 2004)
1. Mizuno S, Kato K, Ono Y, Yano K, Kurosaka H,
Takahashi A, Abeta H, Kushiro T, Miyamoto S,
Kurihara R, Hiki N, Kaminishi M, Iwasaki A,
Arakawa Y. Oral pepermint oil is a useful antispasmodic for double-contrast barium meal examination. J Gastroenterol Hepatol 21: 1297-1301,

2006
2. Takenaka Y, Tsukamoto T, Mizoshita T, Cao X,
Ban H, Ogasawara N, Kaminishi M, Tatematsu T.
Helicobacter pylori infection stimulates intestinalization of endocrine cells in glandular stomachof Mongolia gerbils. Cancer Sci 97: 1015-1022,
2006
3. Nomura S, Nakajima A, Ishimine S, Matsuhashi N,
Kadowaki T, Kaminishi M. Differential expression of peroxisome proliferator-activated receptor
in histologically different human gastric cancer
tissues. J Exp Clin Cancer Res 25: 443-448, 2006
4. Yamashita H, Najagawa K, Tago M, Nakamura N,
Shiraishi K, Mafune K, Kaminishi M, Ohtomo K.
The intergroup/RTOG 85-01 concurrent chemoradiation regimen foe Japanese esophageal cancer.
Hepato-Gastroneterology 53: 863-868, 2006
5. Leys CM, Nomura S, Rudzinski E, Kaminishi M,
Montgomery E, Washington MK, Goldenring JR.
Expression of Pdx-1 in human gastric metaplasia
and gastric adenocarcinoma. Human Pathology
37: 1162-1168, 2006
6. Shimada M, Liu L. Nussler N, Jonas S, Langrehr
JM, Ogawa T, Kaminishi M, Neuhaus P, Nussler
AK: Human hepatocytes are protected from ethanol-induced cytotoxicity by DADA via CYP2E1
inhibition. Toxicology Letters 163(3): 242-249,
2006
7. Nozaki K, Nomura S, Shimizu N, Hiki N, Yoshizawa N, Aiko S, Kubota K, Yamaguchi H, Kurosaka H, Shinozaki A, Mafune K, Fukyama M,
Kaminishi M. Helicobacter pylori-negative /API2-MALT1 translocation-negative low grade
MALT lymphoma. Gastric Cancer 9: 229-234,
2006
8. Hiki N, Shimoyama S, Yamaguchi H, Kubota K,
Kaminishi M. Laparoscopy-assisted pyloruspreserving gastrectomy with quality controlled
lymph node dissection in gastric cancer operation.
J.Am.Coll.Surg. 203 (2):162-169, 2006
9. Maruyama K, Kaminishi M, Hayashi K, Isobe Y,
Honda I, Katai H, Arai K, Kodera Y, Nashimoto A.
Gastric cancer treated in 1991 in Japan: data
analysis of nationwide registry. Gastric Cancer 9:51-66, 2006
10. Hiki N, Shimizu N, Yamaguchi H, Imamura H,
Hatao F, Kaminishi M. Manipulation of the small

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intestine as a cause of the increased inflammatory
response after open compared with laparoscopic
surgery. Br. J Surg 93: 195-204 2006
11. Mizoshita T, Tsukamoto T, Yakenaka Y, Cao X,
Kato S, Kaminishi M, Tatematsu M. Gastric andintestinal phenotypes and histogenesis of advanced glandular stomach cancers in carcinogentreated, Helicobacter pylori-infected Mongolian
gerbils. Cancer Sci 97: 38-44, 2006
12. Kaminishi M. How is it possible to prevent gastricmucosal injury and remnant cancer after distal
gastrectomy. J Gastroenterol 40: 661-663 2005
13. Hiki N, Kaminishi M. Pylorus-preserving gastrectomy in gastric cancer surgery-open andlaparoscopic approaches. Langenbecks Arch Surg390: 442-447, 2005.
14. Kaminishi M. Diversity of gastric carcinogenesis.
Oncology 69 (suppl 1): 1-8, 2005.
15. Kaminishi M, Shimoyama S, Yamaguchi H, Aoki
F, Shimizu N, Nomura S, Hiki N, Mimura T,
Kawahara M, Seto Y, Mafune K. VII. Surgicaltreatment and survival rate of early cancer. In :Early cancer of the gastrointestinal tract, Fujita R,
Jass JR, Kaminishi M, Schlemper RJ eds,
Springer-Verlag, Tokyo, 2005, pp259-272.
16. Kawahara M, Kaminishi M. V. Endoscopic treatment, 2. Colorectal cancer. In : Early cancer of thegastrointestinal tract, Fujita R, Jass JR, Kamnishi
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17. Nomura S, Yamaguchi H, Ogawa M, Wang TC,
Lee JR, Goldenring JR. Alterations in gastricmucosal lineage induced by acute oxyntic atrophy
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G362-G375, 2005
18. Shimoyama S, Imamura K, Hiki N, Yamaguchi H,
Mafune K, Kaminishi M. Performance of outpatient regimen of S-1 in combination with fractional cisplatin for advanced or recurrent gastriccancers: a phase I study. Int J Clin Oncol 10:
251-255, 2005
19. Lu J, Imamura K, Nomura S, Mafune K, Nakajima A, Kadowaki T, Kubota N, Terauchi Y, Ishii
G, Ochiai A, Esumi H, Kaminishi M. Chemopreventive effect of peroxisome proliferator activatedreceptor gamma on gastric carcinogenesis in mice.

Cancer Res 65: 4769-74, 2005
20. Kubota K, Shimizu N, Nozaki K, Takeshita Y,
Ueda T, Imamura K, Hiki N, Yamaguchi H, Shimoyama S, Mafune K, Kaminishi M. Efficacy of
triple therapy plus cetraxate for the Helicobacter
pylori eradication in partial gastrectomy patients.
Dig Dis Sci 50:842-846, 2005
21. Nozaki K, Tanaka H, Ikehara Y, Cao X, Nakanishi
H, Azuma T, Yamazaki S, Yamaoka Y, Shimizu N,
Mafune K, Kaminishi M, Tatematsu M. Helicobacter pylori-dependent NF-kappa B Activation in
newly established Mongolian gerbil gastric celllines. Cancer Sci 96: 170-175, 2005
22. Fujimoto M, Shimizu N, Martyn JA, Ueki K, Kaneki M. A role for iNOS in fasting hyperglycemia
and impaired insulin signaling in the lover ofobese diabetic mice. Diabetes 54:1340-1348, 2005
23. Shimoyama S, Seto Y, Yasuda H, Mafune K,
Kaminishi M. Concepts, rationale, and current
outcomes of less invasive surgical strategies forearly gastric cancer: data from a quarter-century
of experience in a single institution. World J Surg
29: 58-65, 2005
24. Greengauz-Roberts O, Stoppler H, Nomura S,
Yamaguchi H, Goldenring JR, Podolsky RH, Lee
JR, Dynan WS. Saturation labeling with cysteine-reactive cyanine fluorescent dyes provides
increased sensitivity for proten expression profiling of laser microdissected clinical specimens･Proteomics 5: 1746-1757, 2005
25. Shimizu N, Tatematsu M, Kaminishi M. Hekicobacter pylori and gastric carcinoma. In : The Diversity of Gastric Carcinoma, Kaminishi M, Takubo K, Mafune K eds, Springer-Verlag, Tokyo,
2005, pp75-86
26. Yamaguchi H, Lee JR, Goldenring JR, Kaminishi
M. Fundic mucosal change associated with oxyntic atrophy. In : The Diversity of Gastric Carcinoma, Kaminishi M, Takubo K, Mafune K eds,
Springer-Verlag, Tokyo, 2005, pp87-96
27. Shimoyama S, Kaminishi M. Current treatment
strategies for early gastric cancer. In : The Diversity of Gastric Carcinoma, Kaminishi M, Takubo
K, Mafune K eds, Springer-Verlag, Tokyo, 2005,
pp253-270
28. Kaneda A, Sakatani T, Lacobuzio-Donahue CA,
Carter MG, Witzel SB, Okano H, Ko MSH, Ohis-

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son R, Longo DL, Feinberg AP. Loss of imprinting of IGF2 alters intestinal maturation and tumorigenesis in mice. Science 307: 1976-1978,
2005
29. Nomura S, Settle SH, Leys C, Means AL, Peek R,
Leach SD, Wright CV, Coffy RJ, Goldenring JR.
gastric fundus epithelium associated with Menetrier’s disease and TGFa overexpression. Gastroenterology 128:1278-1291, 2005
30. Takahashi Y, Kurabayashi R, Endo H, Nomura S,
Kaminishi M, Tange T. Des-gamma carboxy
prothrombin (PIVKA-II) – and alpha-fetoprotein(AFP)-producing gastric cancer. J Gastroenterol
40: 432-433, 2005
31. Ogawa M, Nomura S, Varro A, Wang TC, Goldenring JR. Altered metaplastic response ofwaves-2 EGF receptor mutant mice to acuteoxyntic atrophy. Am J Physiol Gastrointest Liver
Physiol 2005 (in print)
32. Kaminishi M, Takubo K, Mafune K eds. The Diversity of Gastric Carcinoma. Springer-Verlag,
Tokyo, 2005
33. Cao X, Tsukamoto T, Nozaki K, Shimizu N,
Mizoshita T, Kumagai T, Kaminishi M, Tatematsu
M. Eradication of Helicobacter pylori induces
apoptosis and inhibits proliferation of heterotopic
proliferative glands in infected Mongolian gerbils.
Cancer Sci 95: 827-877, 2004
34. Cao X, Tuskamoto T, Nozaki K, Mizoshita T,
Ogasawara N, Tanaka H, Takenaka M, Kaminishi
M, Tatematsu M. β-Cathenin gene alteration inglandular stomach adenocarcinomas in N-methylN-nitrosoures-treated and Helicobacter pyloriinfected Mongolian gerbils. Cancer Sci 95:487490, 2004
35. Lu J, KunimotoS, Yamazaki Y, Kaminishi M,
Esumi H. Kigamicin D, a novel anticancer agent
based on a new anti-austerity strategy targetingcancer cells’ tolerance to nutrient starvation.
Cancer Sci 95:547-552, 2004
36. Kaneda A, Kaminishi M, Sugimura T, Ushijima T.
Decreased expression of the seven ARP2/3 complex genes in human gastric cancers, Cancer Lett
212:203-210, 2004
37. Kaneda A, Kaminishi M, Sugimura T, Ushijima T.
Lysyl oxidase is a tumor-suppressor gene inactivated by methylation and loss of heterozygosity inhuman gastric cancers. Cancer Res 64: 6410-6415,
2004
38. Kaneda A, Tsukamoto T, Takamura-Enya T, Watanabe N, Kaminishi M, Sugimura T, Tatematsu M,
Ushijima T. Frequent hypomethylation in multiple
promoter CpG ilands is associated with global
hypometylation, but not with frequent promoter
hypermethylation. Cancer Sci 95: 58-64, 2004
39. Kanmori M, Mafune K, Hirashima T, Kawahara
M, Hashimoto M, Ogawa T, Ohta H, Hashinoto H,
Kaminishi M. Forty-three cases of obturator hernia. Am J Surg 187: 548-552, 2004
40. Hiki N, Takeshita Y, Kubota K, Tsuji E, Yamaguchi H, Shimizu N, Imamura K, Shimoyama S,
Mafune K, Kaminishi M. A seasonal variation in
the onset of postoperative adhesive small bowel
obstruction is related to changes in the climate.
Dig Liver Dis 36:125-129, 2004
41. Mizoshita T, Inada K, Tsukamoto T, Nozaki K,
Joh T, Itoh M, Yamamura Y, Ushijima T, Nakamura S, Tatematsu M. Expression of the intestine-specific transcription factors, Cdx 1 and Cdx
2, correlats shift to an intestinal phenotype in gastric cancer cells. J Cancer Res Clin Oncol
130:29-36,2004
42. Shimoyama S, Yasuda H, Hashimoto M, Tatsutomi Y, Aoki F, Mafune K, Kaminishi M. Linear
array endoscopic ultrasonography for preoperative
staging performance in gastric cardia cancer. Gastrointestinal Endoscopy 60:50-55, 2004
43. Shimoyama S, Aoki F, Kawahara M, Yahagi N,
Motoi T, Kuramoto S, Kaminishi M. Early gastriccancer development in a familial adenomatous
polyposis patient. Dig Dis Sci 49:260-265, 2004
44. Shimoyama S, Seto Y, Aoki F, Ogawa T, Toma T,
Endo H, Itouji T, Kaminishi M. A case of gastriccancer with metastasis to the gingiva. J Gastroenterol Hepatol 19:831-835, 2004
45. Nomura S, Kaminishi M, Takagi N, Esumi H.
Analysis of promotor region of X-linked pgk-1
gene polymorphisms : Evidence for polyclonalityof adult mouse gastric glands, Dig Dis Sci 49:
218-223, 2004
46. Nomura s, Baxter T, Yamaguchi H, Leys C, Varapetian AB, Fox JG, Lee JR, Wang TC, Goldenring
JR Spasmolytic polypeptide expressing metaplasia
to pre-neoplasia in H.felis-infected mice. Gas-

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troneterology 127: 582-594, 2004
47. Houghton JM, Stoicov C, Nomura S, Rogers AB,
Carlson J, Li H, Cai X, Fox JG, Goldenring JR
Wang TC. Gastric cancer originating from bonemarrow derived cells. Science 306: 1568-1571,
2004
48. Matsuhashi N, Nakajima A, Nomura S, Kaminishi
M. Inflammatory fibrinoid polyps of the stomachand Helicobacter pylori.J Gastroenterol Hepatol
19: 346-347, 2004
49. Kusakai G, Suzuki A, Ogura T, Kaminishi M,
Esumi H. Strong association of ARK5 with tumor
invasion and metstasis J Exp Cli Cancer Res 23:
263-268, 2004
50. Mimura T, Kaminishi M, Kamm MA. Diagnostic
evaluation of patients with faecal incontinence ata specialist institution. Dig Surg 21: 235-241,
2004

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Department of Hepatobiliary
Pancreatic Surgery andDepartment of Artificial Organ
and Transplantation Surgery
Professor
Masatoshi Makuuchi,MD

Associate Professor
Norihiro Kokudo, MD,

Yasuhiko Sugawara, MD

Lecturer
Yoshifumi Beck, MD,

Hiroshi Imamura, MD

Associates
Masami Minagawa, MD,
Kiyoshi Hasegawa, MD,
Junichi Kaneko, MD,
Takuya Hashimoto, MD,

Katsutoshi Naruse, MD,
Sumihito Tamura, MD,
Yasuji Seyama, MD,
Junichi Arita, MD

Wei Tang, MD,
Taku Aoki, MD,
Yuichi Matsui, MD,

Homepage
Organization
We specialize in hepato-pancreato-biliary surgery
and liver transplantation. The Hepatobiliary Pancreatic Surgery Division and Artificial Organ and Transplantation Surgery Division precede the Second Department of Surgery, which was established in 1893. A
professor and chairman, two associate professors,
three lecturers, and nine associates take part in inpatient and outpatient care as well as teaching and research activities. Department of plastic surgery, anesthesiology and staff of intensive care unit assist us inperforming liver transplantation. Research on artificial
liver is actively performed by Dr. Katsutoshi Naruse.

Clinical Activities
We shared around 60 beds mainly on the A9 northfloor ward with hepatobiliary pancreatic surgery andtransplantation division, high care unit and intensive
care unit on the A4 floor. Each inpatient is taken careof by senior and junior specialist surgeons and a resident in the field of his or her disease throughout thepre- and postoperative periods. Staff members are responsible for the entire care of the patients on a
24-hour-a-day basis. Elective operations are carriedout on Monday, Wednesday and Friday.
Form January 1996 to December 2006, the PediatricSurgery Division and our department performed
around 380 living donor and one deceased donor livertransplantation. The operative mortality is around 5%.
Clinical conferences are held every day in which thelaboratory data and clinical status of the transplants
are discussed. staff’s ward round for inpatients is performed on Tuesday, Thursday and holidays. Out patient clinic is conducted in collaboration with otherdepartment of surgery. We have both general and special outpatient clinic. Specialist surgeons in liver198

transplantation surgery are in service on Monday,
Tuesday and Thursday.

Teaching Activities
We take part in clinical lectures and bed-side
teaching for medical students in cooperation with theother departments. Bed-side teaching is provided to
the fifth and sixth grade students on a man-to-man
basis with staff members. During a three-week period
each student learns the basic way of thinking for correct diagnosis and treatment, fundamental techniquesof radiological examinations and laboratory data, andpre- and postoperative patient care.
Doctor course students are doing research work
under the supervision of the professor and the staff
members. If they think it necessary, they can participate in clinical patient care as a junior specialist surgeon.
Residents learn basic patient care and operative
procedures at the university hospital. Subsequently
they are sent to subsidiary hospitals for two years tolearn further surgical activities. After this postgraduate
training course they decide whether they take a doctor
course.

References (2006)
1

Takayasu K, Arii S, Ikai I, Omata M, Okita K,
Ichida T, Matsuyama Y, Nakanuma Y, Kojiro M,
Makuuchi M, Yamaoka Y; Liver Cancer Study
Group of Japan. Prospective cohort study of transarterial chemoembolization for unresectable
hepatocellular carcinoma in 8510 patients. Gastroenterology 2006 Aug;131(2):461-9.
2 Hasegawa K, Takayama T, Ijichi M, Matsuyama Y,
Imamura H, Sano K, Sugawara Y, Kokudo N,
Makuuchi M. Uracil-tegafur as an adjuvant for
hepatocellular carcinoma: a randomized trial.
Hepatology 2006 Oct;44(4):891-5.
3 Midorikawa Y, Yamamoto S, Ishikawa S, Kamimura N, Igarashi H, Sugimura H, Makuuchi M,
Aburatani H. Molecular karyotyping of humanhepatocellular carcinoma using single-nucleotide
polymorphism arrays. Oncogene 2006 Sep 7;25(40):5581-90.
4 Ito H, Funahashi S, Yamauchi N, Shibahara J,

Midorikawa Y, Kawai S, Kinoshita Y, Watanabe A,
Hippo Y, Ohtomo T, Iwanari H, Nakajima A, Makuuchi M, Fukayama M, Hirata Y, Hamakubo T,
Kodama T, Tsuchiya M, Aburatani H. Identification of ROBO1 as a novel hepatocellular carcinoma antigen and a potential therapeutic and diagnostic target. Clin Cancer Res 2006 Jun 1;12
(11 Pt 1):3257-64.
5 Tsujino T, Isayama H, Sugawara Y, Sasaki T,
Kogure H, Nakai Y, Yamamoto N, Sasahira N,
Yamashiki N, Tada M, Yoshida H, Kokudo N,
Kawabe T, Makuuchi M, Omata M. Endoscopic
management of biliary complications after adultliving donor liver transplantation. Am J Gastroenterol 2006 Oct;101(10):2230-6.
6 Yamazaki S, Miki K, Takayama T, Hasegawa K,
Sata M, Midorikawa Y, Aburatani H, Makuuchi M.
Hepatic gene induction in murine bone marrow
after hepatectomy. J Hepatol 2006 Feb;44(2):325-33.
7 Okazaki M, Asato H, Takushima A, Nakatsuka T,
Sarukawa S, Inoue K, Harii K, Sugawara Y, Makuuchi M. Hepatic artery reconstruction withdouble-needle microsuture in living-donor livertransplantation. Liver Transpl 2006 Jan;12 (1):46-50.
8 Hasegawa K, Sugawara Y, Makuuchi M. Which is
better to overcome the portal steal phenomenon in
auxiliary partial orthotopic liver transplantation:
inflow or outflow occlusion? Liver Transpl 2006
Apr;12 (4):692-3.
9 Sugawara Y, Makuuchi M. Safe liver harvestingfrom living donors. Liver Transpl 2006 Jun;12(6):902-3.
10 Yamashiki N, Sugawara Y, Tamura S, Kaneko J,
Nojiri K, Omata M, Makuuchi M. Selection ofliver-transplant candidates for adult-to-adult living donor liver transplantation as the only surgicaloption for end-stage liver disease. Liver Transpl
2006 Jul;12(7):1077-83.
11 Sugawara Y, Makuuchi M, Tamura S, Matsui Y,
Kaneko J, Hasegawa K, Imamura H, Kokudo N,
Motomura N, Takamoto S. Portal vein reconstruction in adult living donor liver transplantation using cryopreserved vein grafts. Liver Transpl 2006
Aug;12(8):1233-6.
12 Sugawara Y, Makuuchi M. Adult liver transplan-

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tation using live ABO-incompatible grafts in
Western countries. Liver Transpl 2006 Sep;12(9):1324-5.
13 Hashimoto M, Sugawara Y, Tamura S, Kishi Y,
Matsui Y, Kaneko J, Makuuchi M. T-tube drainage
for biliary stenosis after living donor liver transplantation. Transplantation 2006 Jan 27;81(2):293-5.
14 Kaneko J, Sugawara Y, Maruo Y, Sato H, Tamura
S, Imamura H, Kokudo N, Makuuchi M. Livertransplantation using donors with Gilbert syndrome. Transplantatio. 2006 Jul 27;82(2):282-5.
15 Sugawara Y, Kaneko J, Makuuchi M. Cyclosporin
a for treatment of hepatitis C virus after livertransplantation. Transplantation 2006 Aug 27;82(4):579-80.
16 Aramaki O, Sugawara Y, Kokudo N, Takayama T,
Makuuchi M. Branch patch reconstruction inliving donor liver transplantation. Transplantation
2006 Dec 15;82(11):1541-3.
17 Torzilli G, Montorsi M, Del Fabbro D, Palmisano
A, Donadon M, Makuuchi M. Ultrasonographically guided surgical approach to liver tumours
involving the hepatic veins close to the caval confluence. Br J Surg 2006 Oct;93(10):1238-46.
18 Otani T, Matsukura A, Takamoto T, Seyama Y,
Shimizu Y, Shinomiya M, Usui H, Gorelick FS,
Makuuchi M. Effects of pancreatic duct ligation
on pancreatic response to bombesin. Am J Physiol
Gastrointest Liver Physiol 2006 Apr;290(4):G633-9.
19 Sugawara Y, Makuuchi M. Living donor livertransplantation: present status and recent advances.
Br Med Bull. 2006 Feb 10;75-76:15-28.
20 Ikeda M, Hasegawa K, Akamatsu N, Minagawa M,
Imamura H, Sugawara Y, Kokudo N, Makuuchi M.
Pancreaticoduodenectomy after esophageal andgastric surgery preserving right gastroepiploic
vessels. Arch Surg 2006 Feb;141(2):205-8.
21 Minagawa M, Yamamoto J, Miwa S, Sakamoto Y,
Kokudo N, Kosuge T, Miyagawa S, Makuuchi M.
Selection criteria for simultaneous resection inpatients with synchronous liver metastasis. Arch
Surg 2006 Oct;141(10):1006-123.
22 Akamatsu N, Sugawara Y, Tamura S, Imamura H,
Kokudo N, Makuuchi M. Regeneration and function of hemiliver graft: right versus left. Surgery

2006 Jun;139(6):765-72.
23 Matsukura A, Otani T, Takamoto T, Usui H, Goto
Y, Makuuchi M. Intracellular activation of trypsinogen in rat pancreatic acini after supramaximal
secretagogue stimulation: cysteine protease andserine protease activity. Pancreas 2006 Mar;32(2):197-204.
24 Saiura A, Yamamoto J, Koga R, Sakamoto Y, Kokudo N, Seki M, Yamaguchi T, Yamaguchi T,
Muto T, Makuuchi M. Usefulness of LigaSure forliver resection: analysis by randomized clinical
trial. Am J Surg 2006 Jul;192(1):41-5.
25 Torzilli G, Montorsi M, Palmisano A, Del Fabbro
D, Gambetti A, Donadon M, Olivari N, Makuuchi
M. Right inferior phrenic vein indicating the righthepatic vein confluence into the inferior vena cava.
Am J Surg 2006 Nov;192(5):690-4.
26 Ishizawa T, Sugawara Y, Hasegawa K, Ikeda M,
Tamura S, Makuuchi M. Extent of hepatectomy
on splenic hypertrophy and platelet count in live
liver donors. Clin Transplant 2006 Mar-Apr;20(2):234-8.
27 Matsui Y, Sugawara Y, Tsukada K, Kishi Y, Shibahara J, Makuuchi M. Aspergillus thyroiditis in aliving donor liver transplant recipient. J Infect2006 Dec;53(6):e231-3.
28 Kishi Y, Sugawara Y, Tamura S, Kaneko J, Kokudo N, Makuuchi M. Impact of incidentallyfound hepatocellular carcinoma on the outcome ofliving donor liver transplantation. Transpl Int
2006 Sep;19(9):720-5.
29 Tamura S, Sugawara Y, Kaneko J, Yamashiki N,
Kishi Y, Matsui Y, Kokudo N, Makuuchi M. Systematic grading of surgical complications in live
liver donors according to Clavien's system.
Transpl Int 2006 Dec;19(12):982-7.
30 Sakamoto Y, Kosuge T, Shimada K, Sano T, Hibi
T, Yamamoto J, Takayama T, Makuuchi M. Clinical significance of extrahepatic bile duct resection
for advanced gallbladder cancer. J Surg Oncol
2006 Sep 15;94(4):298-306.
31 Ishizawa T, Sugawara Y, Hasegawa K, Ikeda M,
Akahane M, Ohtomo K, Makuuchi M. Hepatobiliary and pancreatic: splenic artery aneurysm after
liver transplantation. J Gastroenterol Hepatol
2006 Jul;21(7):1213.
32 Hashimoto T, Sugawara Y, Tamura S, Hasegawa

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K, Kishi Y, Kokudo N, Makuuchi M. Estimationof standard liver volume in Japanese living liver
donors. J Gastroenterol Hepatol 2006 Nov;21(11):1710-3.
33 Qu X, Yuan Y, Xu W, Chen M, Cui S, Meng H, Li
Y, Makuuchi M, Nakata M, Tang W. Caffeoyl
pyrrolidine derivative LY52 inhibits tumor invasion and metastasis via suppression of matrix
metalloproteinase activity. Anticancer Res 2006
Sep-Oct;26(5A):3573-8.
34 Ikai I, Takayasu K, Omata M, Okita K, Nakanuma
Y, Matsuyama Y, Makuuchi M, Kojiro M, Ichida T,
Arii S, Yamaoka Y; Liver Cancer Study Group ofJapan. A modified Japan Integrated Stage score
for prognostic assessment in patients with hepatocellular carcinoma. J Gastroenterol 2006 Sep;41(9):884-92.
35 Seyama Y, Sano K, Tang W, Kokudo N, Sakamoto
Y, Imamura H, Makuuchi M. Simultaneous resection of liver cell adenomas and an intrahepatic
portosystemic venous shunt with elevation of serum PIVKA-II level. J Gastroenterol 2006 Sep;41(9):909-12.
36 Kusaka K, Imamura H, Tomiya T, Takayama T,
Makuuchi M. Expression of transforming growth
factor-alpha and -beta in hepatic lobes after
hemihepatic portal vein embolization. Dig Dis Sci
2006 Aug;51(8):1404-12.
37 Kobayashi T, Imamura H, Aoki T, Sugawara Y,
Kokudo N, Makuuchi M. Morphological regeneration and hepatic functional mass after righthemihepatectomy. Dig Surg 2006;23(1-2):44-50.
38 Satou S, Sugawara Y, Matsui Y, Kaneko J, Kishi Y,
Imamura H, Kokudo N, Makuuchi M. Preoperative estimation of right lateral sector graft bythree-dimensional computed tomography. Transplant Proc 2006 Jun;38(5):1400-3.
39 Akamatsu N, Sugawara Y, Tamura S, Matsui Y,
Hasegawa K, Imamura H, Kokudo N, Makuuchi
M. Hemophagocytic syndrome after adult-to-adultliving donor liver transplantation. Transplant Proc
2006 Jun;38(5):1425-8.
40 Akamatsu N, Sugawara Y, Tamura S, Kakeno J,
Togashi J, Makuuchi M. Renal impairment after
living donor liver transplantation. Transplant Proc
2006 Jun;38(5):1474-6.
41 Akamatsu N, Sugawara Y, Tamura S, Kaneko J,

Togashi J, Makuuchi M. Impact of celiac axis
stenosis on living donor hepatectomy. Transplant
Proc. 2006 Nov;38(9):2948-50.
42 Kishi Y, Sugawara Y, Tamura S, Kaneko J, Matsui
Y, Makuuchi M. New-onset diabetes mellitus after
living donor liver transplantation: possible association with hepatitis C. Transplant Proc 2006
Nov;38(9):2989-92.
43 Dulundu E, Sugawara Y, Kishi Y, Akamatsu N,
Kokudo N, Makuuchi M. Phrenic vein dissection
in partial liver graft harvesting. Hepatogastroenterology 2006 Sep-Oct;53(71):778-80.
44 Dulundu E, Sugawara Y, Kishi Y, Akamatsu N,
Kaneko J, Makuuchi M. Model for End Stage
Liver Disease score does not predict graft survival
after living donor liver transplantation. Hepatogastroenterology 2006 Sep-Oct;53(71):781-2.
45 Shindoh J, Kokudo N, Satou S, Sugawara Y, Makuuchi M. Volumetric analyses of venous variations in the left liver using 3D-CT venography.
Hepatogastroenterology 2006 Nov-Dec;53(72):831-5.
46 Hasegawa K, Sugawara Y, Ikeda M, Ishizawa T,
Ohashi K, Makuuchi M. Living donor liver transplantation for epithelioid hemangioendothelioma:
Report of a case. Surg Today 2006;36(11):1024-7.
47 Guo Q, Tang W, Inagaki Y, Midorikawa Y, Kokudo N, Sugawara Y, Nakata M, Konishi T, Nagawa H, Makuuchi M. Clinical significance ofsubcellular localization of KL-6 mucin in primarycolorectal adenocarcinoma and metastatic tissues.
World J Gastroenterol 2006 Jan 7;12(1):54-9.
48 Abe H, Tsuneyama K, Tsukada K, Makuuchi M.
Five-year survival following a medi al pancreatectomy for an invasive ductal carcinoma fromthe body of the pancreas. World J Gastroenterol2006 Feb 7;12(5):822-4.
49 Makuuchi M, Kokudo N. Clinical practice guidelines for hepatocellular carcinoma: the first evidence based guidelines from Japan. World J Gastroenterol 2006 Feb 7;12(5):828-9.
50 Maeda E, Uozumi K, Kato N, Akahane M, Inoh S,
Inoue Y, Beck Y, Goto A, Makuuchi M, Ohtomo K.
Magnetic resonance findings of bile duct adenoma
with calcification. Radiat Med 2006 Jul;24(6):459-62.
51 Sugawara Y, Makuuchi M. Living donor liver201

transplantation to patients with hepatitis C virus
cirrhosis. World J Gastroenterol 2006 Jul 28;12(28):4461-5.
52 Cui SX, Qu XJ, Xie YY, Zhou L, Nakata M, Makuuchi M, Tang W. Curcumin inhibits telomerase
activity in human cancer cell lines. Int J Mol Med
2006 Aug;18(2):227-31.
53 Akamatsu N, Sugawara Y, Tamura S, Matsui Y,
Kaneko J, Makuuchi M. Efficacy of mycofenolate
mofetil for steroid-resistant acute rejection after
living donor liver transplantation. World J Gastroenterol 2006 Aug 14;12(30):4870-2.
54 Qu XJ, Yuan YX, Tian ZG, Xu WF, Chen MH, Cui
SX, Guo Q, Gai R, Makuuchi M, Nakata M, Tang
W. Using caffeoyl pyrrolidine derivative LY52, a
potential inhibitor of matrix metalloproteinase-2,
to suppress tumor invasion and metastasis. Int J
Mol Med 2006 Oct;18(4):609-14.
55 Sugawara Y, Makuuchi M. Liver transplantation
for hepatitis B-related cirrhosis: recent advances.
J Hepatobiliary Pancreat Surg 2006;13(5):378-81.
56 Liu J, Xu WF, Cui SX, Zhou Y, Yuan YX, Chen
MH, Wang RH, Gai RY, Makuuchi M, Tang W,
Qu XJ. Inhibition of human gastric carcinoma cell
growth by atofluding derivative N3-o-toluylfluorouracil. World J Gastroenterol 2006 Nov
14;12(42):6766-70.
57 Akamatsu N, Sugawara Y, Tamura S, Keneko J,
Matsui Y, Hasegawa K, Makuuchi M. Late-onset
acute rejection after living donor liver transplantation. World J Gastroenterol 2006 Nov 7;12(41):6674-7.
58 Shin N, Sugawara Y, Tsukada K, Tamura S, Akamatsu N, Okugawa S, Koike K, Kikuchi K, Makuuchi M. Successful treatment of disseminatedNocardia farcinica infection in a living-donorliver transplantation recipient. Transpl Infect Dis
2006 Dec;8(4):222-5.
59 Minagawa M, Makuuchi M. Treatment of hepatocellular carcinoma accompanied by portal veintumor thrombus. World J Gastroenterol 2006 Dec
21;12(47):7561-7.

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Department of Urology
Professor
Tadaichi Kitamura, M.D.,Ph.D.

Associate Professor
Takumi Takeuchi, M.D.,Ph.D.

Kyoichi Tomita, M.D.,Ph.D.

Lecturer
Haruki Kume, M.D., Ph.D.

Hiroaki Nishimatsu, M.D., Ph.D.

Yutaka Enomoto M.D., Ph.D.

Hiroshi Fukuhara, M.D., Ph.D.

Associate
Shinya Matsumoto, M.D.,
Motofumi Suzuki, M.D., Ph.D.,
Akira Nomiya, M.D.,
Shigenori Kakutani M.D.,

Homepage

Tetsuya Fujimura, M.D., Ph.D.,
Akihiko Matsumoto, M.D., Ph.D.,
Yusuke Sato, M.D.,
Toshio Toyoda M.D.

http:// www.h.u-tokyo.ac.jp/urology/

Introduction and Organization
Urology is a special field of clinical medicine covering the diseases of the adrenal gland, the kidney, theurinary tract and the male genital system by means ofa surgical procedure as well as an approach of internal
medicine. In addition, urology encompasses pediatricurology, neurourology, female urology (especially,
stress incontinence), renal transplantation, renal vascular surgery, endocrine surgery and geriatric urology.
For this reason, urology requires the scientific background of oncology, nephrology, endocrinology, andrology, immunology, pediatrics, histology, microbiology, neurology and gerontology. Now we havecommenced to utilize cellular and molecular biology
to develop the research in urology. It is expected forour department to devote to the scientific progress inthe frontier of urology.
In recent years, we have been taking international
leadership in applying the new and minimally invasive
treatment modalities. They are exemplified by endoscopic management of the diseases in the upper urinary tract, ESWL, or laser lithotripsy for urolithiasis,

hyperthermic and laser therapies for BPH, andlaparoscopic adrenalectomy, nephrectomy, andprostatectomy substituting open procedures.
The professor, associate professors, instructors andassociates are involved in in-patient and out-patientcares and teaching of the students as well as research
activities. Clinical visiting professors are mainly engaged in the teaching.

Clinical activities
There are 44 beds in the ward (8th floor of the central-ward-building). The residents take care of all thepatients on 24-hour a day basis. Associate staff members team up with the residents on a man-to-man basis.
The total number of inpatients was 1,050 from January 2006 to December 2006. More than half ofin-patients suffer from urogenital cancers. Urolothiasis, benign prostatic hyperplasia, urinary incontinence and other many diseases are treated.
Elective operations are performed on Tuesday,

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Wednesday, and Thursday. A total of 1,096 operations
were performed in 2006. The main operations are total
cystectomy 19, radical prostatectomy 79, radical
nephrectomy 20, transurethral resection of the bladdertumor (TUR-Bt) 121, transurethral resection of theprostate (TUR-P) 27, laparoscopic surgery 37.
A weekly clinical conference is held for discussing
cases with difficult problems in detail and the besttreatment is chosen for each case. Furthermore at the
weekly professor’s round on Wednesday, data of all inpatients are presented and appropriate treatment
strategies are recommended for them.
In out-patient clinic, services are provided from
Monday to Friday. Patients assigned to specialized
services as andrology, neurourology, urolithiasis, kidney and kidney transplantation receive sophisticatedcare on the particular day of the week.
The total number of out-patients was 2,8438 patient-days from January 2006 to December 2006.

Teaching activities
Systematic urological lectures are provided forsecond year medical students. Both clinical lecturesand bed side teaching are scheduled for third andfourth year medical students. Thirteen times of systematic lectures are performed by professor, associate
professors and instructors concerning their specialties.
Bed side teaching is concentrated on practical careof the patients. Teachers give lectures mainly regarding pre- and post-operative management, indication ofoperation, surgical anatomy and surgical techniques.

Research activities
There are 9 research groups with different clinicaland research activities shown as follows. Our basic
principles for research are in accord with the trends inmodern medicine; improvement of quality of life,
minimally invasive treatment, application of modern
technology and/or basic science and cost-effectiveness.
There are approximately 25 publications in English
each year.
Nephrology group
Urolithiasis group
Kidney Transplantation group

Oncology group
Endourology group
Neurourology and Geriatric urology group
Andrology and Endocrinology group
Immunology group
Virology group

References
1. Takahashi S, Tajima A, Matsushima H, Kawamura
T, Tominaga T, Kitamura T. Clinical efficacy of anα 1a/d–adrenoceptor blocker (naftopidil) on
overactive bladder symptoms in patients with benign prostatic hyperplasia. Int J Urol 2006; 13:
15-20.
2. Takasaka T, Kitamura T, Sugimoto C, Guo J,
Zheng H-Y, Yogo Y. Phylogenetic analysis of major African genotype (Af2) of JC virus : Implications for origin and dispersals of modern Africans.
Am J Phys Anthropol 2006; 129: 465-472.
3. Takahashi S, Yokoyama H, Yanai Y, Kurimoto M,
Ohta N, Kitamura T. Interferon-related mental
deterioration after craniotomy for removal of metastatic renal cancer. Int J Urol 2006; 13: 282-284.
4. Takeda R, Nishimatsu H, Suzuki E, Satonaka H,
Nagata D, Oba S, Sata M, Takahashi M, Yamamoto Y, Terauchi Y, Kadowaki T, Kangawa K,
Kitamura T, Nagai R, Hirata Y : Ghrelin improves
renal function in mice with ischemic acute renal
failure. J Am Soc Nephrol 2006; 17: 113-121.
5. Fukuhara H, Matsumoto A, Kitamura T, Takeuchi
T. Neutralization of interleukin-2 retards thegrowth of mouse renal cancer. BJU Int 2006; 97:1314-1321.
6. Yamada D, Kikuchi S, Williams YN, Sakurai-Yageta M, Masuda M, Maruyama T, Tomita
K, Gutmann DH, Kakizoe T, Kitamura T, Kanai Y,
Murakami Y. Promoter hypermethylation of thepotential tumor suppressor DAL-1/4.1B gene inrenal clear cell carcinoma. Int J Cancer 2006; 118:
916-923.
7. Nukuzuma S, Takasaka T, Zheng H-Y, Zhong S,
Chen Q, Kitamura T, Yogo Y. Subtype-I BK
polyomavirus strains grow more efficiently inhuman renal epithelial cells than subtype-IV
strains. J Gen Virol 2006; 87: 1893-1901.
8. Takasaka T, Goya N, Ishida H, Tanabe K, Toma H,

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Fujioka T, Omori S, Zheng H-Y, Chen Q, Nukuzuma S, Kitamura T, Yogo Y. Stability of the BK
polyomavirus genome in renal transplant patients
without nephropathy. J Gen Virol 2006; 87:
303-306.
9. Fujimura T, Minowada S, Kishi H, Hamasaki K,
Saito K, Kitamura T. Acute pericarditis as a resultof unusual metastasis of the visceral pleura in apatient with testicular seminoma. Int J Urol 2006;
13: 653-654.
10. Yamada D, Yoshida M, Williams YN, Fukami T,
Kikuchi S, Masuda M, Maruyama T, Ohta T, Nakae D, Maekawa A, Kitamura T, Murakami Y.
Disruption of spermatogenic cell adhesion andmale infertility in mice lacking TSLC1/IGSF4, an
immunoglobulin superfamily cell adhesion molecule. Mol Cell Biol 2006; 26: 3610-3624.
11. Takeuchi T, Suzuki M, Kumagai J, Kamijo T, Sakai M, Kitamura T. Extracellular matrix dermatopontin modulates prostate cell growth in vivo.
J Endocrinol 2006; 190: 351-361.
12. Ishikawa A, Shiraishi K, Matsumoto S, Kumagai J,
Nishimatsu H, Tago M, Kume H, Tomita K, Takahashi S, Takeushi T, Nakagawa K, Kitamura T.
Transperineal interstitial permanent prostatebrachytherapy : The University of Tokyo Hospital
experience of initial ten cases. Jpn J Urol Surg
2006; 19: 861-864.
13. Takahashi S, Chen Q, Ogushi T, Fujimura T, kumagai J, Matsumoto S, Hijikata S, Tabata Y, Kitamura T. Periurethral injection of sustainedrelease basic fibroblast growth factor (FGF) improves sphincteric contractility of the rat urethra
denervated by botulinum-A toxin. J Urol, 2006;
176: 819-823.
14. Yamada Y, Fujimura T, Takahashi S, Takeuchi T,
Takazawa Y, Kitamura T : Tubulovillous adenoma
developing after urinary reconstruction using ileal
segments. Int J Urol 2006; 13: 1134-1135.
15. Takasaka T, Ohta N., Zheng H-Y, Ikegaya H, Sakurada K, Kitamura T, Yogo Y. JC polyomavirus
lineages common among Kiribati Islanders : Implications for human dispersal in the Pacific. Anthropol Sci, 2006; 114: 133-140.
16. Ota S, Hishinuma M, Yamauchi N, Goto A,
Morikawa T, Fujimura T, Kitamura T, Kodama T,
Aburatani H, Fukayama M. Oncofetal protein

glypican-3 in testicular germ-cell tumor. VichowsArch, 2006; 449: 308-314.
17. Chen Q, Zheng H-Y, Zhong S, Ikegaya H, He H-X,
Wei W, He Y-Y, Kobayashi N, Honjo T, Takasaka
T, Takahashi S, Kitamura T, Yogo Y. Subtype IVof the BK polyomavirus is prevalent in East Asia.
Arch Virol 2006; 151: 2419-2429.
18. Nishimoto Y, Takasaka T, Hasegawa M, Zheng
H-Y, Chen Q, Sugimoto C, Kitamura T, Yogo Y.
Evolution of BK virus based on complete genome
data. J Mol Evol, 2006; 63: 341-352.
19. Ota S, Hishinuma M, Yamauchi N, Goto A,
Morikawa T, Fujimura T, Kitamura T, Kodama T,
Aburatani H, Fukayama M. Oncofetal protein
glypican 3 in testicular germ cell tumor. VirchowsArchiv, 2006; 449(3):308-14.
20. Tsurumaki Y, Tomita K, Kume H, Yamaguchi T,
Morikawa T, Takahashi S, Takeuchi T, Kitamura T.
Predictors of seminal vesicle invasion before
radical prostatectomy. Int J Urol 2006; 13:1501-1508.
21. Ikegaya H, Saukko PJ, Tertti R, Metsärinne KP,
Carr MJ, Crowley B, Sakurada K, Zheng H-Y,
Kitamura T, Yogo Y. Identification of a genomic
subgroup of BK virus spread in European populations. J Gen Virol 2006; 87: 3201-3208.
22. Ikeda T, Yoshizawa S, Tosaki M, Allen J S, Takagi
S, Ohta N, Kitamura T, Matsumoto Y. Cloudcavitation control for lithotripsy using high intensity focused ultrasound. Ultrasound in Med.＆
Biol. 2006; 32: 1383-1397.
23. Akaza H, Hinotsu S, Usami M, Ogawa O, Kagawa
S, Kitamura T, Tsukamoto T, Naito S, Hirao Y,
Murai M, Yamanaka H, Namiki M. The case forandrogen deprivation as primary therapy for earlystage disease : results form J-Cap and CaPSURETM. J Urol 2006; 176: S47-S49.
24. Ishikawa A, Tanaka M, Ohta N, Ozono S, Kitamura T. Prevention of interstitial fibrosis of allograft by angiotensin Ⅱ blockade. Transplant P
2006; 38: 3498-3501.

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Department of Surgical Oncology
Professor
Hirokazu Nagawa, M.D., Ph.D.

Lecturer
Joji Kitayama, M.D., Ph.D.

Clinical Lecturer
Shoichi Kaisaki, M.D.

Associate
Yoshiki Takei, M.D., Ph.D.,
Hironori Ishigami, M.D.,
Sinsuke Saito, M.D., Ph.D.,
Takamitsu Kanazawa, M.D.,

Giichiro Tsurita, M.D., Ph.D.,
Soichiro Ishihara, M.D., Ph.D.,
Sinsuke Kazama, M.D., Ph.D.,
Akio Hidemura, M.D., Ph.D.

Homepage http://all-1su.umin.jp/
Introduction and Organization
In 1995, a new system for postgraduate education
was introduced. The First Department of Surgery was
reorganized to form the Department of Surgical Oncology and the Department of Vascular Surgery. The
staff of the Department of Surgical Oncology consistsof one Professor, two Lecturers and eight Associates.
The outpatient office is located on the third floor of
the Outpatient Building. The ward is situated on theeighth floor of the Ward Building. The administrative
office and research laboratories are located in the Administration and Research Building. Current activitiesof the Department of Surgical Oncology in clinicalpractice, education, and research are summarized asfollows.

Clinical activities
The Department of Surgical Oncology provides
comprehensive evaluation, diagnosis, treatment andmanagement for adult patients with both general andoncologic surgical problems, in the ambulatory as wellas inpatient setting. Additionally, surgical specialities
in the department include the treatment of benign andmalignant disorders of the breast and management ofmalignancies of the gastrointestinal tract (esophageal,
gastric, and colorectal). The department is also wellknown for its innovative therapy for inflammatory
bowel disease. Department specialists have expertisein biological cancer immunotherapy, chemotherapy
for a variety of malignancies, and radiotherapy forrectal cancer. The outpatient clinic is open from
Monday through Friday, and twenty-four-hour consultation is available for urgent or emergency problems.
The outpatient clinic is specialized in the upper GI
tract, lower GI tract, and breast diseases. The Department was responsible for 365 surgically treated inpatients in the year of 2006. On Monday, Wednesday
and Friday mornings, pre- and post-surgery conferences are held, and the Professor's Round takes place
after the conference every Wednesday. Operating days
are Monday, Tuesday and Thursday. In addition to theclinical conferences, research conferences are held
every Monday and Saturday morning. Each research
unit holds its own conference every week.

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Teaching activities
The Department of Surgical Oncology also offers afellowship in surgical oncology for well-qualified
surgeons who have completed their training in generalsurgery and wish to further specialize in surgical oncology. The Department of Surgical Oncology has a
Surgical Oncology Training Program and provides
broad reaching experience in technical aspects of diagnosis, treatment and management for adult patientswith both surgical and oncologic problems, development of surgical judgment, and increasing knowledge
about routine and complex conditions. In addition, thededicated staff allows multiple opportunities for academic development both along clinical and basic scientific lines.
In the undergraduate education program, our department plays a role in the systemic and clinical lectures and the bedside learning program for 3rd year
medical students, in cooperation with other departments of surgery. In the systemic lectures on surgery
for the fiscal year of 2005, various fields were covered
such as surgical oncology and immunology, injury,
somatic reaction to surgery, infectious diseases, shock,pre- and post-surgical management and nutrition. In
the clinical lectures, we presented many diseases suchas colon cancer, colonic polyp, colonic polyposis andulcerative colitis. In the postgraduate education program, new residents are trained to become qualified
surgeons. In addition to pre- and post-surgery clinicalconferences, the residents are expected to attend research conferences and seminars, which are held periodically. They are also asked to present cases atclinical meetings, which are held locally such as the
local meeting of the Japanese Society of Gastroenterology.

Research activities
At present, our department has three major research
units divided according to the members’ special fields.
The clinical and academic interests of our department
are the upper and lower gastrointestinal tract, and thebreast. We also apply the techniques used in molecularand cellular biology to our research. The following are
the major themes under research.
1) Preoperative radiotherapy in lower rectal cancer

2)
3)
4)
5)
6)

Cancer surveillance in ulcerative colitis
Carcinogenesis in ulcerative colitis
Laparoscopically assisted colon surgery
Local immunity in colorectal cancer
Genetic analysis of colorectal cancer and adenoma
7) Prognostic factor of early colorectal cancer8) Surveillance program following colectomy forcolorectal cancer
9) The mechanism of liver metastasis of colorectal
cancer10) Carcinogenesis in superficial early colorectal
cancer11) Genetic alterations in synchronous and metachronous multiple colorectal cancers12) Microsatellite instability and a risk of developing
multiple colorectal cancers13) Dendritic cell Immunotherapy for advanced cancer14) Cancer Immunotherapy targeting to the tumor
vessels
15) Angiogenesis inhibition in peritoneal metastasisof gastric cancer16) Role of LPA S1P and Edg receptors in tumor metastasis17) Lipid metabolism in carcinogenesis and tumor
progression18) Sentinel lymph node identification using nanobeads
19) Genetic analysis on sensitivity to chemotherapeutic agents20) Hemostasis and fibrinolysis in Oncology21) Leptin and adiponectin in Oncology22) Intraabdominal chemotherapy for peritoneal metastasis of gastric cancer23) Angiogenic progenitor cells and antigen presentation
24) Fibloblast Growth Factor (FGF) in inflammatory
bowel disease25) Genetic analysis of undifferentiated colorectal
cancer26) High Frequency Ultrasonography (HIFU) for
solid cancer27) Endocannabinoid in acticancer therapy

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References
1. Yamaguchi H, Ishikawa M, Hatanaka K, Uekusa T,
Ishimaru M, Nagawa H. Occult breast cancer presenting as axillary metastases. Breast. 2006 Apr;15(2):259-62.
2. Asakage M, Tsuno NH, Kitayama J, Kawai K, Okaji
Y, Yazawa K, Kaisaki S, Osada T, Watanabe T, Takahashi K, Nagawa H. Early-outgrowth of endothelial progenitor cells can function as antigenpresenting cells. Cancer Immunol Immunother. 2006
Jun;55(6):708-16.
3. Sako A, Kitayama J, Shida D, Suzuki R, Sakai T,
Ohta H, Nagawa H. Lysophosphatidic acid (LPA)induced vascular endothelial growth factor (VEGF)
by mesothelial cells and quantification of hostderived VEGF in malignant ascites. J Surg Res.
2006 Jan;130(1):94-101.
4. Yamashita H, Kitayama J, Shida D, Yamaguchi H,
Mori K, Osada M, Aoki S, Yatomi Y, Takuwa Y,
Nagawa H. Sphingosine 1-phosphate receptor expression profile in human gastric cancer cells: differential regulation on the migration and proliferation. J Surg Res. 2006 Jan;130(1):80-7.
5. Mori K, Kitayama J, Shida D, Yamashita H, Watanabe T, Nagawa H. Lysophosphatidic acid-induced
effects in human colon carcinoma DLD1 cells are
partially dependent on transactivation of epidermal
growth factor receptor. J Surg Res. 2006 May;132(1):56-61.
6. Sasaki S, Watanabe T, Kobunai T, Nagawa H. Effectof cystathionine beta-synthase variant 844ins68bp
and methylenetetrahydrofolate reductase A1298C
polymorphisms in xenografts on 5-FU efficacy anddoubling time. Cancer Lett. 2006 Sep 28;241(2):256-62.
7. Yamashita H, Kitayama J, Ishigami H, Yamaguchi H,
Souma D, Nagano R, Nagawa H. Multiple gastrictube carcinomas after curative oesophagectomy. Dig
Liver Dis. 2006 Mar;38(3):214-5.
8. Yamashita H, Kitayama J, Shida D, Ishikawa M,
Hama K, Aoki J, Arai H, Nagawa H. Differential
expression of lysophosphatidic acid receptor-2 in
intestinal and diffuse type gastric cancer. J Surg
Oncol. 2006 Jan 1;93(1):30-5.
9. Konishi T, Watanabe T, Nagawa H. Pelvic drainage
should be a routine for TME with or without radia-

tion. Ann Surg. 2006 Jan;243(1):141-2.
10. Watanabe T, Kiyomatsu T, Kanazawa T, Kazama Y,
Kojima T, Tanaka J, Tanaka T, Nagawa H. Weekly
oxaliplatin and preoperative radiotherapy as a newneoadjuvant therapy for locally-advanced rectal
cancer. Ann Oncol. 2006 Jul;17(7):1173.
11. Kazama S, Watanabe T, Ajioka Y, Kanazawa T, Nagawa H. Tumour budding at the deepest invasive
margin correlates with lymph node metastasis in
submucosal colorectal cancer detected by anticytokeratin antibody CAM5.2. Br J Cancer. 2006 Jan
30;94(2):293-8.
12. Watanabe T, Kanazawa T, Kazama Y, Tanaka J, Tanaka T, Nagawa H. Microsatellite instability in adenoma as a possible marker to identify HNPCC patients. Am J Gastroenterol. 2006 Jan;101(1):204.
13. Konishi T, Sasaki S, Watanabe T, Kitayama J, Nagawa H. Overexpression of hRFI inhibits 5fluorouracil-induced apoptosis in colorectal cancer
cells via activation of NF-kappaB and upregulationof BCL-2 and BCL-XL. Oncogene. 2006 May 25;25(22):3160-9.
14. Konishi T, Watanabe T, Nagawa H. Formalin application in the treatment of chronic radiation-induced
hemorrhagic proctitis induces acute deterioration of
mucosal blood flow. Dis Colon Rectum. 2006
Apr;49(4):530-1.
15. Yamashita H, Ishimaru M, Yamaguchi H, Yamauchi
H, Sugiura A, Kitayama J, Nagawa H. Massive
postoperative polyuria following total gastrectomy
for gastric cancer. J Anesth. 2006;20(1):36-9.
16. Okaji Y, Tsuno NH, Kitayama J, Sakurai D, Tsuchiya N, Saito S, Takegami K, Tsuchiya T, Kawai K,
Yazawa K, Asakage M, Yoneyama S, Yamada J,
Tokunaga K, Takahashi K, Nagawa H. Effects ofdown-regulating the Id genes in human colorectal
cancer cells on early steps of haematogenous metastasis. Eur J Cancer. 2006 Mar;42(5):668-73.
17. Konishi T, Watanabe T, Kishimoto J, Nagawa H.
Risk factors for anastomotic leakage after surgery
for colorectal cancer: results of prospective surveillance. J Am Coll Surg. 2006 Mar;202(3):439-44.
18. Okaji Y, Tsuno NH, Saito S, Yoneyama S, Tanaka M,
Nagawa H, Takahashi K. Vaccines targeting tumour
angiogenesis--a novel strategy for cancer immunotherapy. Eur J Surg Oncol. 2006 May;32(4):363-70.
19. Kazama Y, Watanabe T, Kanazawa T, Kazama S,

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Tada T, Tanaka J, Nagawa H. Mucinous colorectal
cancers with chromosomal instability: a biologicallydistinct and aggressive subtype. Diagn Mol Pathol.
2006 Mar;15(1):30-4.
20. Watanabe T, Kanazawa T, Kazama Y, Tanaka J, Tanaka T, Ishihara S, Nagawa H. SMAD4 levels andallelic imbalance in 18q21 in colorectal cancer. Clin
Cancer Res. 2006 Mar 1;12(5):1654.
21. Tabuchi M, Kitayama J, Nagawa H. Hypertriglyceridemia is positively correlated with the development of colorectal tubular adenoma in Japanese men.
World J Gastroenterol. 2006 Feb 28;12(8):1261-4.
22. Motoyoshi M, Nomura S, Watanabe T, Kyo K, Watanabe H, Negishi S, Nagawa H. Biliary cystadenocarcinoma presenting as recurrent cholangitis. Surgery. 2006 Mar;139(3):448-50.
23. Konishi T, Watanabe T, Shibahara J, Nagawa H.
Surveillance colonoscopy should be conducted inpatients with colorectal Shistosomiasis even after
successful treatment of the disease. Int J Immunopathol Pharmacol. 2006 Jan-Mar;19(1):245-6.
24. Watanabe T, Komuro Y, Kiyomatsu T, Kanazawa T,
Kazama Y, Tanaka J, Tanaka T, Yamamoto Y, Shirane M, Muto T, Nagawa H. Prediction of sensitivityof rectal cancer cells in response to preoperative radiotherapy by DNA microarray analysis of gene expression profiles. Cancer Res. 2006 Apr 1;66(7):3370-4.
25. Sasaki S, Watanabe T, Kobunai T, Konishi T, Nagase H, Sugimoto Y, Oka T, Nagawa H. hRFI overexpressed in HCT116 cells modulates Bcl-2 family
proteins when treated with 5-fluorouracil. Oncol
Rep. 2006 May;15(5):1293-8.
26. Ohnishi T, Watanabe T, Nozawa H, Nagawa H. Telomerase subunit immunoreactivity and recurrencein colorectal cancer. Hepatogastroenterology. 2006
Mar-Apr;53(68):188-91.
27. Konishi T, Watanabe T, Morikane K, Fukatsu K,
Kitayama J, Umetani N, Kishimoto J, Nagawa H.
Prospective surveillance effectively reduced rates ofsurgical site infection associated with elective colorectal surgery at a university hospital in Japan. InfectControl Hosp Epidemiol. 2006 May;27(5):526-8.
28. Shinozaki M, Watanabe T, Sato H, Nagawa H.
Chronic colitis promotes tumor development. Oncol
Rep. 2006 Jun;15(6):1485-90.
29. Kojima T, Watanabe T, Hata K, Shinozaki M, Yo-koyama T, Nagawa H. Cytomegalovirus infection inulcerative colitis. Scand J Gastroenterol. 2006 Jun;
41(6):706-11.
30. Yamashita H, Kitayama J, Kanno N, Yatomi Y, Nagawa H. Hyperfibrinogenemia is associated withlymphatic as well as hematogenous metastasis andworse clinical outcome in T2 gastric cancer. BMC
Cancer. 2006 Jun 1;6:147.
31. Kitayama J, Morota T, Kaisaki S, Nakayama H,
Ishigami H, Yamashita H, Ishikawa M, Shibata K,
Takamoto S, Nagawa H. Complete coverage of insitu aortograft by total omental pedicle flap as themost reliable treatment of aortoesophageal fistula.
Am J Surg. 2006 Jul;192(1):130-4.
32. Watanabe T, Kanazawa T, Kazama Y, Tanaka J, Tanaka T, Ishihara S, Nagawa H, Benatti P, Ponz deLeon M, Gafa R, Lanza G, Barana D, Oliani C. Adjuvant chemotherapy in colorectal cancer patientswith microsatellite instability. Clin Cancer Res. 2006
Jun 15;12(12):3866-7.
33. Asakage M, Tsuno NH, Kitayama J, Tsuchiya T,
Yoneyama S, Yamada J, Okaji Y, Kaisaki S, Osada T,
Takahashi K, Nagawa H. Sulforaphane induces inhibition of human umbilical vein endothelial cells
proliferation by apoptosis. Angiogenesis. 2006;9(2):83-91.
34. Konishi T, Watanabe T, Nagawa H. Treatment oflocal ischaemia: another promising approach forgastrointestinal complications of pelvic radiotherapy.
Gut. 2006 Aug;55(8):1209.
35. Watanabe T, Sunami E, Hata K, Nagawa H. Onestage completely laparoscopic restorative proctocolectomy for ulcerative colitis complicated withsigmoid colon cancer--a case report. Minim Invasive
Ther Allied Technol. 2006;15(4):253-6.
36. Ishikawa M, Kitayama J, Nagawa H. Expression
pattern of leptin and leptin receptor (OB-R) in human gastric cancer. World J Gastroenterol. 2006 Sep
14;12(34):5517-22.
37. Watanabe T, Kobunai T, Toda E, Yamamoto Y, Kanazawa T, Kazama Y, Tanaka J, Tanaka T, Konishi T,
Okayama Y, Sugimoto Y, Oka T, Sasaki S, Muto T,
Nagawa H. Distal colorectal cancers with microsatellite instability (MSI) display distinct gene expression profiles that are different from proximal MSI
cancers. Cancer Res. 2006 Oct 15;66(20):9804-8.
38. Konishi T, Watanabe T, Kishimoto J, Nagawa H.

209Elective colon and rectal surgery differ in risk factors for wound infection: results of prospective surveillance. Ann Surg. 2006 Nov;244(5):758-63.
39. Tanaka T, Watanabe T, Kazama Y, Tanaka J, Kanazawa T, Kazama S, Nagawa H. Chromosome 18q
deletion and Smad4 protein inactivation correlatewith liver metastasis: A study matched for T- and Nclassification. Br J Cancer. 2006 Dec 4;95(11):1562-7.
40. Tsuchiya T, Watanabe T, Konishi T, Nagawa H.
Toxic megacolon associated with Crohn's disease.
Gastrointest Endosc. 2006 Dec;64(6):1012-3.
41. Motoyoshi M, Sugiyama M, Atomi Y, Kimura W,
Nagawa H. Effect of a selective thromboxane A2
synthetase inhibitor on the systemic changes induced by circulating pancreatic phospholipase A2. J
Gastroenterol. 2006 Nov;41(11):1094-8.
42. Nozawa H, Watanabe T, Nagawa H. Phosphorylation of ribosomal p70 S6 kinase and rapamycin sensitivity in human colorectal cancer. Cancer Lett.
2007 Jun 18;251(1):105-13.
43. Sako A, Kitayama J, Ishikawa M, Yamashita H,
Nagawa H. Impact of immunohistochemically identified lymphatic invasion on nodal metastasis inearly gastric cancer. Gastric Cancer. 2006;9(4):295302.

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Department of Vascular Surgery
Professor
Hirokazu Nagawa, M.D., Ph.D.

Associate Professor
Tetsuro Miyata, M.D., Ph.D.

Associate
Kunihiro Shigematsu, M.D., Ph.D.,

Juno Deguchi, M.D., Ph.D.,

Hideo Kimura, M.D., Ph.D.,

Seiji Nishikage, M.D.

Homepage

http://all-1su.umin.jp/

Introduction and Organization
In 1995, a new system for postgraduate education
was introduced. The First Department of Surgery was
reorganized to form the Department of Vascular Surgery and the Department of Surgical Oncology. The
staff of the Department of Vascular Surgery consistsof one Professor, one Associate Professor and four
Associates. The outpatient office is located on thethird floor of the Outpatient Building. The ward issituated on the eighth floor of the Ward Building. The
administrative office and research laboratories arelocated in the Administration and Research Building.
Current activities of the Department of Surgical Oncology in clinical practice, education, and research aresummarized as follows.

Clinical activities
The Department of Vascular Surgery has an extensive clinical program in both primary and tertiary carefor vascular problems, and manages patients with peripheral arterial occlusion, abdominal and thoracoabdominal aortic aneurysms, peripheral aneurysm,
visceral arterial occlusion, carotid artery disease andcommon disorders of the venous circulation such asvaricose veins and venous leg ulcers. State-of-the-art
techniques of percutaneous transluminal angioplasty,
angioscopy and intraoperative ultrasonography areavailable for the treatment of peripheral arterial disease. The outpatient clinic is open from Monday
through Friday, and twenty-four-hour consultation isavailable for urgent or emergency problems.
The department was responsible for 274 surgicallytreated inpatients in the year of 2006. Included in thedepartment is the non-invasive Clinical Vascular
Laboratory, which sees over 500 patients per year,with broad reaching expertise in peripheral vasculardiagnostic modalities. Also the department has an active angiography program, which encompasses all
aspects of diagnostic and therapeutic intervention inover 500 patients per year and a full range of othersupport and collaborative services.
On Monday, Wednesday and Friday mornings, preand post-surgery conferences are held. Operating days
are Monday, Tuesday and Thursday. The vascular angiographic conference is held every Tuesday evening.

Teaching activities
The Department of Vascular Surgery also offers afellowship in vascular surgery for well-qualified surgeons who have completed their training in generalsurgery and wish to further specialize in vascular surgery. The Department of Vascular Surgery has a Vascular Surgery Training Program and provides broadreaching experience in technical aspects of vascularsurgery, development of surgical judgment, and in-211creasing knowledge about routine and complex conditions. In addition, the dedicated staff offers multiple
opportunities for academic development both along
clinical and basic scientific lines.
In the undergraduate education program, the Department of Vascular Surgery plays a role in the systemic and clinical lectures and the bedside learning
program for 3rd year medical students, in cooperation
with other departments of surgery. In the postgraduate
education program, new residents are trained to become qualified surgeons in our department. In addition to pre- and post-surgery clinical conferences, theresidents are expected to attend research conferences
and seminars, which are held periodically.

11) Mechanism of ischemic preconditioning of thelimb12) Development of a new drug delivery system fortherapeutic angiogenesis13) Introduction of gene into vascular wall cells byelectroporation
14) Application of nano technology for in-vivo genetransfer to vascular wall cells
15) Basic research for arterialization of artificial organ
16) Development of a new method for evaluation oflimb ischemia
17) Develolpment of a new machine for autoevaluation of in-vivo endothelial function

Research activities

References

The Department of Vascular Surgery includes major
research laboratories for academic development bothalong clinical and basic scientific lines. The clinicalvascular laboratories are approaching completely noninvasive testing for vascular disorders, analyzing essential physiologic information about the specificproblems being addressed. The basic vascular laboratories are actively performing research on endothelial
biology, the mechanism of intimal hyperplasia, microcirculation, application of gene therapy to vascularsurgery and vascular prosthesis development. The
following are the major themes under research.
1) Three-dimensional visualization abdominal aorta
2) Pathophysiology of the development of the aneurysm
3) Prevention of the anastomotic intimal hyperplasia
4) Pathophysiology of stent restenosis
5) Analyzing the intercellular transmission of thegrowth signal in the vascular smooth muscle cells6) Tissue oxygen dynamics assessed by near infrared
spectroscopy7) Application of near infrared spectroscopy to bloodflow monitoring during carotid endarterectomy8) Lower limb arterial circulation in a patient with
end-stage renal disease assessed by near infrared
spectroscopy9) Microvascular permeability changes induced by
PAF10) Pharmacological analysis of microcirculation in
in-vivo model

1. Miyahara T, Koyama H, Miyata T, Shigematsu H,
Inoue J, Takato T, Nagawa H. Inflammatory responses involving tumor necrosis factor receptor-associated factor 6 contribute to in-stent lesion formation in a stent implantation model of
rabbit carotid artery. J Vasc Surg. 2006 Mar;43(3):592-600.
2. Yamamoto K, Miyata T, Nagayoshi M, Akagi D,
Hosaka A, Miyahara T, Ishii S, Shigematsu K,
Shigematsu H, Nagawa H. Carotid endarterectomy may reduce the high stroke rate for patientswith the disease of abdominal aorta and peripheral arteries. Int Angiol. 2006 Mar;25(1):35-9.
3. Hosaka A, Miyata T, Shigematsu H, Deguchi JO,
Kimura H, Nagawa H, Sato O, Sakimoto T, Mochizuki T. Spontaneous mesenteric hemorrhage
associated with Ehlers-Danlos syndrome. J Gastrointest Surg. 2006 Apr;10(4):583-5.
4. Akagi D, Ishii S, Kitagawa T, Nagawa H, Miyata
T. Popliteal arterial aneurysm associated with
Klippel-Trenaunay syndrome: case report andliterature review. J Vasc Surg. 2006 Jun;43(6):1287-9.
5. Miyahara T, Miyata T, Shigematsu K, Deguchi J,
Kimura H, Ishii S, Nagawa H. Clinical outcome
and complications of temporary inferior vena
cava filter placement. J Vasc Surg. 2006 Sep;44(3):620-4.
6. Yamamoto K, Miyata T, Nagawa H. The highprevalence of colorectal neoplasms in preopera-

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tive patients with abdominal aortic aneurysm orperipheral artery disease. Eur J Vasc Endovasc
Surg. 2007 Apr;33(4):397-400.
7. Yamamoto K, Miyata T, Onozuka A, Koyama H,
Ohtsu H, Nagawa H. Plantar flexion as an alternative to treadmill exercise for evaluating patients with intermittent claudication. Eur J Vasc
Endovasc Surg. 2007 Mar;33(3):325-9.
8. Yamamoto KK, Miyata T, Momose T, Nagayoshi
M, Akagi D, Hosaka A, Miyahara T, Ishii S, Kimura H, Deguchi J, Shigematsu K, Shigematsu H,
Nagawa H. Reduced vascular reserve measured
by stressed single photon emission computed
tomography carries a high risk for stroke in patients with carotid stenosis. Int Angiol. 2006
Dec;25(4):385-8.
9. Akagi D, Oshiro H, Yamamoto K, Kimura H,
Taniwaka K, Shigematsu H, Nagawa H, Miyata T.
Popliteal venous aneurysm with repeated episodes of pulmonary embolism. Case report andliterature review. Int Angiol. 2006 Dec;25(4):427-32.
10. Ishikawa M, Kitayama J, Kaisaki S, Okamoto H,
Miyata T, Akahane M, Nagawa H. Image of themonth: left gastric aneurysm. Gastroenterology.
2006 Jan;130(1):7, 288.

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Department of Metabolic Careand Endocrine Surgery
Professor
Michio Kaminishi MD. PhD.

Associate Professor
Toshihisa Ogawa MD. PhD, Yoshikazu Mimura MD. PhD (Surgical Center)

Lectuler
Hajime Kanauchi MD. PhD.

Associates
Makoto Kammori MD.PhD, Ei-ichi Tsuji MD. Junko Yamamura MD.

Homepage
Organization
Our section is staffed by one professor, one associate professor, one lecturer and two assistants and twoor three residents. Official activities of our sections
are run by same schedule to Department of Gastrointestinal Surgery.

Clinical Activities
Endocrine Surgery is not familiar with Japanese yet,however, it has been a long time to be studied this area
by top level surgeons in western countries. We havestarted our activities for this area since 1987 and ourdepartment has been established with reconstructionof our hospital structure in 1997. This is a result of thegrowth of demand nationally and internationally and it
is caused by not only treatment for malignant disease
but also functional one or giving more attention toquality of life.
Professional skill and wider knowledge of endocrine system are required for this area. Diseases wetreat at our department are breast, thyroid, parathyroid,
and adrenal gland. In additional to treatment for malignant cases of these diseases, we perform surgicalprocedures for hyperfunctional diseases. We co-workwith the department of endocrinological internal
medicine and have about 60 surgical procedures annually in total.
In breast surgery, more than a half of the mammary
cancer patients undergo the breast-preserving surgery.
In addition, sentinel node navigation surgery has been
adopted, resulting in better quality of postoperative
life. Reconstruction surgery for the breast cancer islikely to provide much better QOL. In this field, we
have started collaboration with the Department of
Plastic Surgery. Chemotherapy, hormone therapy andmolecular- targeting therapy play important roles intreatment of the breast cancer. We have accumulated a
lot of experience and achievement in this field.
Our clinical themes are 1) establishment of safe
procedures for endocrinｅ diseases without complications; 2) diagnosis and treatment of micro-breast
lesions under ultrasonographic guides; 3) preoperative
diagnosis for thyroid neoplasmas and breast tumors
based on telomere length and telomerase activity using Q-Fish.

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Research Acitivities
Our section has been studying about the most fundamental issues to surgery, i.e., “surgical stress”
which means postoperative physiological and endocrinological internal reaction and “nutritional support”
for the postoperative patients. These are subjects to
reduce the intra- and post-operative stresses thatwould be risky for the patients. Our section is like apioneer for this area in Japan and we establishedJapanese Society for Surgical Metabolism and Nutrition in 1965. Graduate students organize main study
group and we have presentations at some international
conferences each year.
The focus of our research is “surgical metabolism
and nutrition” and “the body’s adaptive responses during postoperative recovery”. In addition, we have been
engaged in the project of chemo-sensitivity of breast
cancer and of treatment for breast tumors byhigh-energy ultrasound. Research details follow.
1) Mechanisms of cross tolerance among different
stresses (endotoxin - hypoxia/ hypoxia - hypoxia)
after surgery
2) Role of catecholamines in adaptation to surgicalstresses such as endotoxemia3) Bacterial translocation after anti-cancer chemotherapy4) Gender difference is a modulating factor for postoperative morbidity
5) Measurement of endotoxin activity through Tolllike receptor 46) Role of oxygen on local and systemic protein metabolism after major surgery7) Ischemic preconditioning preserves renal dysfunction after ischemia-reperfusion
8) Telomere-length and telomere activity in the thyroid and the breast tumors9) Application of Q-Fish in diagnosis of the thyroid
and the breast tumors10) Chemo-sensitivity in breast cancer

Publications (2002 - March 2004)
1. Shimada M, Liu L. Nussler N, Jonas S, Langrehr
JM, Ogawa T, Kaminishi M, Neuhaus P, Nussler

AK: Human hepatocytes are protected from ethanol-induced cytotoxicity by DADA via CYP2E1
inhibition. Toxicology Letters 163(3): 242-249,
2006
2. Kammori M, Tsuji E, Kaminishi M, et al. Invasive
breast carcinoma in a patient with Behcet’s disease: The pathological findings existed vasculitis
with carcinoma. Breast Cancer (in press)
3. Hiki N, Shimizu N, Yamaguchi H, Imamura H,
Hatao F, Kaminishi M. Manipulation of the small
intestine as a cause of the increased inflammatory
response after open compared with laparoscopic
surgery. Br. J Surg 93: 195-204 2006
4. Kammori M, Fukami T, Ogawa T, Tsuji E, Takubo
K, Nakajima J, Kaminishi M: Giant mediastinal
cystic parathyroid adenoma. J Clin Endocrinol
Metab 91: 1635-1636, 2006
5. Kammori M, Onoda N, Kaminsihi M, et al: Specific subtelomere loss on chromosome der(11)t(3;11)(q23;q23)x2 in anaplastic thyroid cancer
cell line OCUT-1. Int J Mol Med 18: 9-17, 2005
6. Kammori M, Izumiyama N, Hashimoto M, Nakamura K, Okano T, Kurabayashi R, Honma N,
Ogawa T, Kaminishi M, Takubo K. Expression ofhuman telomerase reverse transcriptase gene andprotein, and of estrogen and progesterone receptors, in breast tumors: Preliminary data from neoadjuvant chemotherapy. Int J Oncol 27: 12571263, 2005
7. Fujimoto M, Shimizu N, Martyn JA, Ueki K, Kaneki M. A role for iNOS in fasting hyperglycemia
and impaired insulin signaling in the lover ofobese diabetic mice. Diabetes 54:1340-1348, 2005
8. Ogawa T, Kanauchi H, Kammori M, Terada K,
Shimada M, Mimura Y, Kaminishi M. Characteristic ultrasound findings of oxyphilic cell tumors
in thyroid gland Thyroidol 16:186-188, 2005
9. Hatao F, Hiki N, Mimura Y, Ogawa T, Kojima J,
Mafune K, Hawkins LD, Muroi M, Tanamoto K,
Kaminishi M. The influence of super-resistence
using synthetic lipopolysaccharide receptor agonist rescues fatal endotoxemiaa in rats without
excessive immunosuppression. Shock 23: 365-370,
2005
10. Asai K, Buurman WA, Reutelingsperger CPM,
Schtte B, Kaminishi M. Modular effects of estradiol on ethanol-induced apoptosis in human intes-

215

tinal epithelial cells. Scand J Gastroenterol 40:
326-335, 2005
11. Hatao F, Muroi M, Hiki N, Ogawa T, Mimura Y,
Kaminishi M, tanamoto K. Prolonged Toll-likereceptor stimulation leads to down-regulation of
IRAK-4 protein. J Leukoc Biol 76: 904-908, 2004
12. Ding H, Schertzer M, Wu X, Gertsenstein M,
Selig S, Kammori M, Pourval R, Poon S, Vulto I,
Chavez E, Tam PPL, Nagy A, Lansdorp PM.
Regulation of murine telomere length by Rtel: An
essential gene encoding a helicase-like protein.
Cell 117: 872-886, 2004

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Department of Dermatology
Professor
Kunihiko Tamaki, M.D., Ph.D.

Associate Professor
Kanako Kikuchi, M.D., Ph.D.

LecturerMayumi Komine, M.D., Ph.D.
Hidehisa Saeki, M.D., Ph.D.
Norihito Yazawa, M.D.,Ph.D

Takafumi Kadono,M.D., Ph.D.
Takahiro Watanabe, M.D., Ph.D.

Associate
Takashi Kakinuma, M.D. Ph.D.
Yayoi Tada, M.D., Ph.D
Yuichiro Tsunemi, M.D., Ph.D.
Andre Le Pavoux, M.D.

Homepage

Yuki Ohno, M.D.
Ryuichi Ashida, M.D.
Yousaku Minatani, M.D.
Etsuko Mori, M.D.

http://www.h.u-tokyo.ac.jp/der/Introduction and Organaization
The Department of dermatology celebrated its
100th anniversary in 1990. Originally it was foundedas the Department of Dermatology and Urology,
which also encompassed veneology. In 1946 the Department of Dermatology was separated from that of
Urology. Regarding venereology, sexually transmitted
diseases only related to skin manifestations are now
dealt in our department.
The professor, one associate professors, five lecturers and eight associates take part in inpatient and outpatient cares as well as research and teaching activities. Twenty doctors who basically belong to our department are currently out in affiliated hospitals
mainly engaged in clinical works there Additionally,
five staff members are abroad at present, mainly involved in advanced research activities in cell biology
and molecular biology.

Clinical Activities
In the out-patient clinic we see around 200 patientsa day. Incisional and excisional biopsies are frequently
performed under local anesthesia at the outpatient operation facilities belonging to our department. Daily
discussions are made for initially consulted cases
when they are rather difficult to diagnose, by all staff
members including Professor and Associate Professors.
Furthermore, retrospective clinical and histologicaldiscussions are held regularly, which always gives us
invaluable lessons.
Concerning the in-patient clinic, there are about ten
staff members under the supervision of the ward-chief.
Surgical operations such as removal of malignancies
and skin grafting that require general anesthesia arealso performed weekly in the central surgical facilities.

Education
We have ten dermatologist who are studying in the
postgraduate course under the guidance of staff members of our department.
In addition to series of lectures , clinical education
is provided for fifth- and six grade medical students,

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which aims at giving a general introduction for how
make dermatological approaches for diagnosis andtreatment, with a stress on learning how to observeand describe a variety of skin eruptions. Actually thestudents are supposed to see patients in outpatient
clinic every day for an entire week, as well as to participate in the inpatient clinic.

References Activities
Each specialized outpatient service reflects its own
research field in a disease-oriented manner. However,those specialized groups performing their own clinicaland research activities are never exclusive, and there
are increasing communications with other departments
such as internal medicine and blood transfusion service as well as intergroup communications. Recent
advanced techniques in cellular, molecular biology
and our newly established laboratories, will enable us
to organize optimal research conditions.
1. Hoashi T, Muller J, Vieira WD, Rouzaud F, Kikuchi K, Tamaki K, Hearing VJ. The repeat domain of the melanosomal matrix protein
PMEL17/GP100 is required for the formation oforganellar fibers. J Biol Chem 2006;281:21198208.
2. Kikuchi K, Hoashi T, Yazawa N, Tamaki K.
Pseudoscleroderma associated with cancer. ClinExp Dermal 2006;31:381-3.
3. Kikuchi K, Komine M, Takekoshi T, Tamaki K.
Serum uric acid levels in patients with vitiligo receiving narrowband ultraviolet B phototherapy.
Clin Exp Dermatol 2006;32:107-108.
4. Sugaya M, Fang L, Cardones AR, Kakinuma T,
Jaber SH, Blauvelt A, Hwang ST: Oncostatin M
Enhances CCL21 Expression by MicrovascularEndothelial Cells and Increases the Efficiency ofDendritic Cell Trafficking to Lymph Nodes. J
Immunol 177:7665-72, 2006.
5. Saeki H, Tsunemi Y, Asano N, Nakamura K, Sekiya T, Hirai K, Kakinuma T, Fujita H, Kagami S,
Tamaki K: Polymorphisms of GM-CSF gene inJapanese patients with atopic dermatitis. Clin Exp
Dermatol 31: 278-80, 2006.
6. Saeki H, Tamada Y, Watanabe D, Akita Y, Matsumoto Y, Imai C, Tsunemi Y, Kadono T, Maeka-

wa T, Kikuchi K, Hattori N, Kaneko T, WatanabeA, Torii H, Tamaki K: Analysis of gene mutations
in four cases of dermatofibrosarcoma protuberans.
Clin Exp Dermatol 31: 441-4, 2006.
7. Tamaki K, Kakinuma T, Saeki H, Horikawa T,
Kataoka Y, Fujisawa T, Sato S, Takehara K, Nakahara T, Fukagawa S, Furue M: Serum levels of
CCL17/TARC in various skin diseases. J Dermatol 33: 300-2, 2006.
8. Saeki H, Tamaki K: Thymus and activation regulated chemokine (TARC) / CCL17 and skin diseases. J Dermatol Sci 43: 75-84, 2006.
9. Saeki H, Nakamura K, Tsunemi Y, Komine M,
Tamaki K: A novel keratin 5 gene mutation(Asp158Val) in a Japanese patient with Köbner
type of epidermolysis bullosa simplex. J Dermatol
33: 692-5, 2006.
10. Hashimoto S, Nakamura K, Oyama N, Kaneko F,
Tsunemi Y, Saeki H, Tamaki K: Macrophagederived chemokine (MDC)/CCL22 produced bymonocyte derived dendritic cells reflects the disease activity in patients with atopic dermatitis. J
Dermatol Sci 44: 93-9, 2006.
11. Saeki H, Tsunemi Y, Fujita H, Kagami Shinji, Sasaki K, Ohmatsu H, Watanabe A, Tamaki K: Prevalence of atopic dermatitis determined by clinical examination in Japanese adults. J Dermatol 33:
817-9, 2006.
12. Tada Y, Asahina A, Takekoshi T, Kishimoto E,
Mitsui H, Saeki H, Komine M, Tamaki K. Interleukin 12 production by monocytes from patientswith psoriasis and its inhibition by ciclosporin A.
Br J Dermatol 154: 1180-1183, 2006.
13. Tada Y, Riedl E, Lowenthal MS, Liotta LA, Briner
DM, Crouch EC, Udey MC. Identification andcharacterization of endogenous Langerin ligands
in murine extracellular matrix. J Invest Dermatol
126: 1549-1558, 2006.
14. Asano Y, Ihn H, Jinnin M, Mimura Y, Tamaki K.
Involvement of alphavbeta5 integrin in the establishment of autocrine TGF-beta signaling in dermal fibroblasts derived from localized scleroderma. J Invest Dermatol. 126:1761-9, 2006.
15. Asano Y, Ihn H, Yamane K, Jinnin M, Tamaki K.
Increased expression of integrin alphavbeta5 induces the myofibroblastic differentiation of dermal fibroblasts. Am J Pathol 168: 499-510, 2006.

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16. Asano Y, Ihn H, Kubo M, Jinnin M, Mimura Y,
Ashida R, Tamaki K. Clinical significance of serum levels of matrix metalloproteinase-13 in patients with systemic sclerosis. Rheumatology(Oxford) 45:303-7, 2006.
17. Asano Y, Ihn H, Maekawa T, Kadono T, Tamaki K.
High-dose intravenous immunoglobulin infusion
in polyarteritis nodosa: report on one case and review of the literature. Clin Rheumatol 25: 396-8,
2006.
18. Tsunemi Y, Saeki H, Nakamura K, Nagakubo D,
Nakayama T, Yoshie O, Kagami S, Shimazu K,
Kadono T, Sugaya M, Komine M, Matsushima K,
Tamaki K. CCL17 transgenic mice show an enhanced Th2-type response to both allergic andnon-allergic stimuli. Eur J Immunol 36: 2116-27,
2006.
19. Jinnin M, Ihn H, Mimura Y, Asano Y, Tamaki K.
Potential regulatory elements of the constitutive
up-regulated alpha2(I) collagen gene in scleroderma dermal fibroblasts.
Biochem Biophys Res Commun 343: 904-9, 2006.
20. Jinnin M, Ihn H, Asano Y, Yamane K, Troja-nowska M, Tamaki K. Upregulation of tenascin-C expression by IL-13 in human dermal fibroblasts via the phosphoinositide 3-kinase/Akt
and the protein kinase C signaling pathways. J
Invest Dermatol 126: 551-60, 2006

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Department of Plastic andReconstructive Surgery
Professor
Isao Koshima, M.D.

Lecturer
Kotaro Yoshimura, M.D.

Associate
Koichi Gonda, M.D.
Takuya Iida, M.D.
Noriyuki Aoi, M.D.

Gentaro Uchida, M.D.,D.D.S
Mitsunaga Narushima, M.D.

Homepage
Organization
The present faculty of the Department of Plastic andReconstructive Surgery consists of 1 professor, 1 associate professor, 1 lecturer, 5 associates and 6 physicians.
There are about 100 doctors in the department, including 16 medical trainees, 8 graduate school students, but
most are serving in rotation at affiliated hospitals.
The outpatient clinic is located on the 3rd floor of theoutpatients building, while there are wards with about
25 available beds on the 10th floor in the New Ward.
Our faculty room is located in the Medical Laboratory
Building and laboratory rooms in the East Laboratory
Building.
The present status of the educational, research andclinical activities of the department is as follows.

Clinical Activities
The outpatient clinic is opened every morning from
Monday to Friday. There are several specialized clinics
for trauma, scars and keloids, facial paralysis, hand,replantation, microsurgery, breasts, head and neck reconstruction, cleft lip and palate, craniofacial malformation, congenital anomalies, vascular malformations,
lymphedema, and cosmetic surgery including cosmetic

dermatology. There are about 2,500 new patients andthe total number of revisiting patients are about 25,000
in a year. In the operating theater over 300 operations
are achieved under general anesthesia, while in theoutpatient clinic about 300 operations are achieved under local anesthesia in a year. Each week, the professor
goes the round of inpatients on Wednesday morning.
Preoperative and postoperative conferences and seminar that all members of the department should attend
are held on Wednesday evening. Research conferences
are held on every Monday and Friday evening.

Teaching Activities
In regard to pregraduate education, the department
has the duty of lecturing to 2nd, 3rd and 4th year medical students, and also of instructing 4th medical students in bed side practice. The subjects taken up in thelectures include general concepts of plastic surgery,wound healing, congenital malformations, skin grafts
and flaps, microsurgery, head and neck reconstruction,
hand surgery, craniomaxillofacial surgery, burn andtrauma, cosmetic surgery, and regenerative medicine. In
the bed side practice the students have the opportunityof seeing various diseases and disorders in the field ofplastic surgery and attending outpatient clinics, surgical222

operations and clinical lectures by faculty members.
For graduate school students, microsurgical training
program is undertaken in the laboratory room. In the
postgraduate course, after completing the 6-year training program, a trainee can sit for the board examinationof the Japan Society of Plastic and Reconstructive Surgery.

Research Activities
Basic and clinical researches are performed in groups.
The major research subjects are as follows:
1) Studies on cell isolation from human tissue such as
adipose, amnion, and placenta.
2) Studies on mechanism of hypermelanogenesis of
the skin.
3) Studies on differentiation induction of human adultstem cells from adipose, amnion, and placenta
4) Characterization of human adult stem cells anddermal papilla cells.
5) Studies on hair regrowth using epidermal stem cells
and dermal papilla cells.
6) Clinical studies on fat regeneration using suctioned
fat tissue and adipose stromal progenitor cells.
7) Studies on biological function of extracellular matrix taken from human adipose tissue.
8) Studies on angiogenesis using human adult stem
cells from adipose.
9) Studies on chondrogenesis and osteogenesis using
human fibrin and adipose stromal cells.
10) Studies on molecular mechanisms of vasculogenesis and angiogenesis in the mouse embryo.
11) Studies on molecular pathogenesis of holoprosencephaly using a mouse model.
12) Studies on MMPs and TIMPs expressed in keloid.
13) Studies on the cultured epidermal cells and the celladhesive function.
14) Studies on clinical application and growth factor
extraction of a fluid from continuous suction drainage.
15) Studies on mechanism of biological effects of retinoids on epidermis and dermis.
16) Studies on regeneration of peripheral nerves.

References (2005-2006)
1: Yamada Y, Nagase T, Nagase M, Koshima I. Gene
expression changes of sonic hedgehog signalingcascade in a mouse embryonic model of fetal alcohol syndrome. J Craniofac Surg. 2005 Nov;16(6):1055-61.
2: Koshima I, Ozaki T, Gonda K, Okazaki M, Asato H.
Posterior tibial adiposal flap for repair of wide,
full-thickness defect of the Achilles tendon. J Reconstr Microsurg. 2005 Nov;21(8):551-4.
3: Nagase T, Gonda K, Inoue K, Higashino T, Fukuda
N, Gorai K, Mihara M, Nakanishi M, Koshima I.
Treatment of lymphedema with lymphaticovenular
anastomoses. Int J Clin Oncol. 2005 Oct;10(5):304-10.
4: Koshima I. Short pedicle superficial inferior epigastric artery adiposal flap: new anatomical findings and the use of this flap for reconstruction of
facial contour. Plast Reconstr Surg. 2005 Sep 15;
116(4):1091-7.
5: Nagase T, Nagase M, Yoshimura K, Fujita T, Koshima I. Angiogenesis within the developing mouseneural tube is dependent on sonic hedgehog signaling: possible roles of motor neurons. Genes Cells.
2005 Jun;10(6):595-604.
6: Kaji N, Nagase T, Nagase M, Koshima I. Changes
in angiogenic gene expression in a case of expanded capillary malformation: does an expanded
capillary malformation grow? Ann Plast Surg. 2005
Jun;54(6):645-50.
7: Koshima I, Fujitsu M, Ushio S, Sugiyama N, Yamashita S. Related Articles, Links Flow-throughanterior thigh flaps with a short pedicle for reconstruction of lower leg and foot defects. Plast Reconstr Surg. 2005 Jan;115(1):155-62.
8: Koshima I, Yamashita S, Sugiyama N, Ushio S,
Tsutsui T, Nanba Y. Successful delayed venous
drainage in 16 consecutive distal phalangeal replantations. Plast Reconstr Surg. 2005 Jan;115(1):149-54.
9: Okazaki M, Suzuki Y, Yoshimura K, Harii K. Construction of pigmented skin equivalent and its application to the study of congenital disorders ofpigmentation. Scand J Plast Reconstr Surg Hand
Surg, 2005 39: 339-43.
10: Mochizuki Y, Ojima K, Uezumi A, Masuda S, Yo-

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shimura K, Takeda S. Participation of bone marrow-derived cells in fibrotic changes in denervatedskeletal muscle. Am J Pathol 2005 166: 1721-1732.
11: Nagase T, Yoshimura K, Aiba E, Matsumoto D,
Sato K, Machino C. Angle-splitting Ostectomy
Followed by Facelift for Elderly Patients with
Prominent Mandibular Angles. Plast Reconstr Surg,2005 115: 633-40.
12: Yoshimura K, Wakita S, Sato K, Kaji N, Aiba E,
Matsumoto D, Yamaoka H, Nagase T. A Clinical
trial of Simultaneous Reconstruction of Breast andWell-Projected Nipple Following Expansion ofBreast Skin. Scand J Plast Reconstr Surg Hand
Surg, 2005 39: 77-84.
13: Matsumoto D, Sato K, Gonda K, Takaki Y, Shigeura T, Sato T, Aiba-Kojima E, Iizuka F, Inoue K,
Suga H, Yoshimura K. Cell-assisted lipotransfer:
supportive use of human adipose-derived cells forsoft tissue augmentation with lipoinjection. TissueEng. 2006 Dec;12(12):3375-82.
14: Sato K, Matsumoto D, Iizuka F, Aiba-Kojima E,
Watanabe-Ono A, Suga H, Inoue K, Gonda K, Yoshimura K. Anti-androgenic therapy using oral spironolactone for acne vulgaris in Asians. Aesthetic
Plast Surg. 2006 Nov-Dec;30(6):689-94.
15: Sarukawa S, Okazaki M, Asato H, Koshima I. Volumetric changes in the transferred flap after anterior craniofacial reconstruction. J Reconstr Microsurg. 2006 Oct;22(7):499-505.
16: Namba Y, Kimata Y, Koshima I, Sugihara S, Sato T.
Fibular osteoadiposal flap for treatment of tibial
adamantinoma: a case report. Acta Med Okayama.
2006 Aug;60(4):233-6.
17: Itano H, Andou A, Date H, Koshima I, Shimizu N.
Chest wall reconstruction with perforator flaps after
wide full-thickness resection. J Thorac Cardiovasc
Surg. 2006 Jul;132(1):e13-4.
18: Koshima I, Nanba Y, Nagai A, Nakatsuka M, Sato
T, Kuroda S. Penile reconstruction with bilateralsuperficial circumflex iliac artery perforator (SCIP)
flaps. J Reconstr Microsurg. 2006 Apr;22(3):13742.
19: Yoshimura K, Sato K, Aiba-Kojima E, Matsumoto
D, Machino C, Nagase T, Gonda K, Koshima I.
Repeated treatment protocols for melasma and acquired dermal melanocytosis. Dermatol Surg. 2006
Mar;32(3):365-71.

20: Yamaoka H, Asato H, Ogasawara T, Nishizawa S,
Takahashi T, Nakatsuka T, Koshima I, Nakamura K,
Kawaguchi H, Chung UI, Takato T, Hoshi K. Cartilage tissue engineering using human auricularchondrocytes embedded in different hydrogel materials. J Biomed Mater Res A. 2006 Jul;78(1):1-11.
21: Yoshimura K, Shigeura T, Matsumoto D, Sato T,
Takaki Y, Aiba-Kojima E, Sato K, Inoue K, Nagase
T, Koshima I, Gonda K. Characterization of freshly
isolated and cultured cells derived from the fatty
and fluid portions of liposuction aspirates. J Cell
Physiol. 2006 Jul;208(1):64-76.
22: Ozkan O, Koshima I, Gonda K. A supermicrosurgical flap model in the rat: a free true abdominal
perforator flap with a short pedicle. Plast Reconstr
Surg. 2006 Feb;117(2):479-85.
23: Nagase M, Nagase T, Koshima I, Fujita T. Criticaltime window of hedgehog-dependent angiogenesis
in murine yolk sac. Microvasc Res. 2006 Mar;71(2):85-90.
24: Nagase T, Nagase M, Yoshimura K, Machida M,
Yamagishi M. Defects in aortic fusion and craniofacial vasculature in the holoprosencephalic mouseembryo under inhibition of sonic hedgehog signaling. J Craniofac Surg. 2006 Jul;17(4):736-44.
25: Yoshimura K, DeMeester J, Hasan JS, Urbanchek
MG, Kuzon WM Jr. Neurovascular transfer does
not cause skeletal muscle fiber degeneration. Plast
Reconstr Surg. 2006 Apr 15;117(5):1455-61.
26: Gonda K, Kikyo N. Nuclear remodeling assay in
Xenopus egg extract. Methods Mol Biol. 2006;348:
247-58.
27: Iida T, Nakagawa M, Asano T, Fukushima C, Tachi
K. Free vascularized lateral femoral cutaneous
nerve graft with anterolateral thigh flap for reconstruction of facial nerve defects. J Reconstr Microsurg. 2006 Jul;22(5):343-8.
28: Kurita M, Aiba E, Matsumoto D, Sato K, Nagase T,
Yoshimura K. Feminizing genitoplasty for treatment of XX male with masculine genitalia. Plast
Reconstr Surg. 2006 May;117(6):107e-111e.
29: Yoshimura K, Sato K, Aiba-Kojima E, Matsumoto
D, Machino C, Nagase T, Gonda K, Koshima I.
Repeated treatment protocols for melasma and acquired dermal melanocytosis. Dermatol Surg. 2006
Mar;32(3):365-71.
30: Yoshimura K, Shigeura T, Matsumoto D, Sato T,

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Takaki Y, Aiba-Kojima E, Sato K, Inoue K, Nagase
T, Koshima I, Gonda K. Characterization of freshly
isolated and cultured cells derived from the fatty
and fluid portions of liposuction aspirates. J Cell
Physiol. 2006 Jul;208(1):64-76.
31: Koshima I, Urushibara K, Fukuda N, Ohkochi M,
Nagase T, Gonda K, Asato H, Yoshimura K. Digitalartery perforator flaps for fingertip reconstructions.
Plast Reconstr Surg. 2006 Dec;118(7):1579-84.

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Department ofOral-Maxillofacial Surgery
Professor
Tsuyoshi Takato, M.D.,Ph.D.

Associate Professor
Takafumi Susami, D.D.S., Ph.D.

Yoshiyuki Yonehara, M.D., Ph.D.

Lecturer
Yoshiyuki Mori, D.D.S., Ph.D.

Hisako Hikiji, D.D.S., Ph.D.,

Ken Tomizuka, D.D.S., Ph.D.

Meiko Ohki, D.D.S., Ph.D.

Associate
Jun-ichi Kuroe, D.D.S.
Nobuhiko Kumazawa, D.D.S.
Katsumi Ohhashi, D.D.S.
Masako Matsuzaki, D.D.S., Ph.D.
Hideto Saijo, D.D.S., Ph.D.
Mamiko Wada, M.S.

Homepage

Yukiko Suzuki, D.D.S.
Gen-ichiro Takagi, D.D.S.
Daichi Chikazu, D.D.S., Ph.D.
Kazumi Ohkubo, D.D.S., Ph.D.
Toru Ogasawara, D.D.S., Ph.D.

http://plaza.umin.ac.jp/%7Eoralsurg/

Introduction and Organization
Department of Oral and Maxillofacial Surgery,commenced by Dr. Hisashi Ishihara in 1900, is one ofthe oldest departments in Graduate School of Medicine,the University of Tokyo. This department consists of awide variety of specialists, including oral surgeons, orthodontists and prosthodontists. We handle all diseases
in the oral-maxillofacial region, such as congenital
anomalies, jaw deformities, benign and malignant tumors, bone fractures and inflammation. Dental care forthe patients who have systemic disorders and are under
medical control is another field of our department.
Multidisciplinary treatment teamed by these specialists
is characteristic and has performed excellent results inclinical works. In research fields, all staffs participate in
the clinical and basic research to support the treatment
scientifically and to develop new treatment protocols,
and we have mainly performed the experimental studies

on the regenerative capacity of tissues, especially bone,
periosteum, cartilage, perichondrium, blood vessels,
nerve, skin, etc. At present, we are focusing on tissue
engineering in research works especially in bone, cartilage, vessels. Professor Takato has established Tissue
Engineering Division in Tokyo University Hospital andour department has two endowment departments: Department of Cartilage and Bone Regeneration (FUJI
SOFT Inc.) and Department of Clinical Vascular Regeneration (Daiichi Sankyo Co., Ltd.) in Tissue Engineering Division. These departments have 1 associate
professor, 1associate, and some graduate students ineach. These staffs are focusing on translational researchworks in maxillofacial regions.

Clinical activities
In the outpatient clinic, we have 12 dental treatment
booths, one operation room and one speech therapy

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room, and treat about 90 patients per day. Dental treatments for systemic diseases are mainly performed inthis clinic. Dental surgeries such as extraction of impacted teeth, amputation of infected dental root andgingivoplasty are performed in the operation room.
Dental implants are also set in an outpatient basis andoften utilized in maxillofacial prosthodontic treatments
in reconstructed jaws after surgical resection of malignant tumors. Facial growth control and tooth movements in patients with congenital facial anomalies suchas cleft lip and palate are the most popular orthodontic
treatment. Pre- and post-surgical orthodontic treatments
combined with surgical correction of dentofacial deformities are another important role. Speech therapy tothe patients with cleft lip and palate are being done byspeech-langage-hearing therapists in the same outpatient clinic.
In the ward, we have about 350 new inpatients and330 cases are operated per year. The main surgical operations are primary closure of cleft lip and palate, secondary bone grafting in alveolar cleft, surgical correction of dentofacial deformities using maxillo- mandibular osteotomies, resection of malignant tumors followed by micro-surgical reconstruction by plastic surgeons, and correction of facial bone fractures. Both forin- and out-patients, we treat by multidisciplinary teamapproach consisted of oral and maxillofacial surgeons,orthodontists and prosthodontists. Recently, we carryout facial bone lengthening by distraction osteogenesis,
and grafting the original artificial bone which is madeby the 3D data of CT and tissue engineering techniquefor patients with dento-facial deformity.

Education
Teaching activities are divided into two parts; forundergraduate medical students and for postgraduate
dental students. For undergraduate students, we make 5
systematic lectures in their second year of specialized
course, and one lecture and one week bedside learningin final year. Through these curriculums, we demonstrate the characteristics and treatments of the diseases
in oral-maxillofacial region. Teaching is focused onfollowing points; congenital anomalies such as cleft lip
and palate and branchial arch syndromes, dentofacial
deformities caused by developmental and acquired
problems, surgical resection and functional reconstruc-tion of benign and malignant tumors, temporomandibular joint disorders, inflammation and maxillofacial
trauma. Minimum dental knowledge concerning jaw
movement, tooth pain, periodontal disease, malocclusion and dental restorations are instructed.
As for postgraduate dental students, we have a twoyears training course. This course aims to train for awide range of dental treatments and to learn about
medical cares. Various specialists instructed dental
treatments for them in outpatient clinic. Carious treatments, periodontal cares and applications of dentures
are taught by prosthodontists. Tooth extractions andorthodontic treatment are instructed by oral surgeons
and orthodontists. Medical cares in the ward are taught
by medical doctors and oral surgeons.

ResearchResearch projects are made both clinically and basically on themes closely related to clinical problems.
The main projects are as follows.
Clinical research:
1） Multidisciplinary treatment of facial deformities inpatients with cleft lip and palate or other congenital
maxillofacial anomalies
2） Multidisciplinary treatment of dentomaxillofacial
deformities, fractures and temporomandibular diseases3） Multidisciplinary treatment of malignant tumors inhead and neck region4） Combined surgical-chemical-radiological treatment
for malignant tumors5） Development of dental implant
6） Effects of arthrocentesis or therapeutic exercisesfor temporomandibular disorders
7） Non-surgical treatment system for facial bone
fractures
8） Bone repair in dentomaxillofacial region using
tissue engineering technique
Basic and experimental research:
1) Osteogenic capacity of periosteum2) Capacity of perichondrial regeneration
3) Osteogenic capacity of growth plate4) Development of various types of new skin flaps
5) Metabolism of poly ADP-ribose in DNA repair and227

cell differentiation
6) Gene analysis of congenital anomalies of oral andmaxillofacial region7) Effect of free radicals on bone metabolism
8) Intracellular calcium handling on osteoblasts9) Differentiation mechanism of osteoblasts in termsof cell cycle molecule10) Osteochondrogenic differentiation of bone marrowderived mesenchymal stem cells by spheroid culture11) Mandibular lengthening by floating bone method
12) Periodontal tissue regeneration on dental implants
13) Characterization of skin derived multipotent stem
cells, especially differentiation mechanism into
neuronal cell
14) Bone and cartilage repair in dentomaxillofacial
region using tissue engineering technique

Publications
1) Chikazu D, Ogasawara T, Ogata N, Saijo H, Koizumi T, Mori Y, Tomizuka K, Yonehara Y, Susami T,
Takato T. Cyclooxygenase-2 Regulates Bone Marrow Stromal Cell Differentiation by Bone Morphogenetic Protein 2. Asian J Oral Maxillofac Surg
2006; 18: 28-34.
2) Hikiji H, Eguchi T, Koizumi T, Saijo H, Chikazu D,
Yonehara Y, Takato T. Simplified nasoalveolar
molding (NAM) technique in Infants with cleft lip
and palate. Asian J Oral Maxillofac Surg 2006; 18:
46-50.
3) Igawa K, Sugimori O, Ohba S, Takato T, Mochizuki M, Sasaki N, Chung UI. Tailor-made tricalcium phosphate bone implant directly fabricated bya three-dimensional ink-jet printer. J Artif Organs
2006; 9: 234-240.
4) Katagiri M, Ogasawara T, Hoshi K, Chikazu D,
Kimoto A, Noguchi M, Sasamata M, Harada S,
Akama H, Tazaki H, Chung UI, Takato T, Nakamura K, Kawaguchi H. Suppression of Adjuvant-Induced Arthritic Bone Destruction by Cyclooxygenase-2 Selective Agents with and without
Inhibitory Potency against Carbonic Anhydrase II.
J Bone Miner Res 2006; 21: 219-227.
5) Kamekura S, Kawasaki Y, Hoshi K, Shimoaka T,
Chikuda H, Maruyama Z, Komori T, Sato S, Takeda S, Karsenty G, Nakamura K, Chung UI, Ka-

waguchi H. Contribution of runt-related transcription factor 2 to the pathogenesis of osteoarthritis inmice after induction of knee joint instability. Arthritis Rheum 2006; 54: 2462-2470.
6) Kugimiya F, Ohba S, Nakamura K, Kawaguchi H,
Chung UI. Physiological role of bone morphogenetic proteins in osteogenesis. J Bone Miner Metab
2006; 24: 95-99.
7) Miyahara T, Koyama H, Miyata T, Shigematsu H,
Inoue J, Takato T, Nagawa H. Inflammatory responses involving tumor necrosis factor receptor-associated factor 6 contribute to in-stent lesion
formation in a stent implantation model of rabbit
carotid artery. J Vasc Surg 2006; 43: 592-600.
8) Mori Y, Eguchi T, Mastuzaki M, Ogihara Y, Susami
T, Chikazu D, Saijyo H, Yonehara Y, Takato T. A
2-stage procedure combining maxillary advancement by distraction technique with mandibular setback surgery in patients with cleft lip and palate.
Int J Oral Maxillofac Surg 2006; 35: 594-597.
9) Oki M, Iida T, Mukohyama H, Tomizuka K, Takato T, Taniguchi H. The vibratory characteristics
of obturators with different bulb height and form
designs. J Oral Rehabil 2006; 33: 43-51.
10) Sakanishi H, Hoshi K, Nakajima S, Akune T, Takeshita K, Yamamoto M, Kawaguchi H, Nakamura
K, Seichi A. Vertebral hemangioma compressing
the thoracic spinal cord: application of computer-aided navigation and intraoperative spinal
sonography for surgery through anterior andposterior approaches. J Orthop Sci 2006; 11: 29411) 297.
Shinoda Y, Yamaguchi M, Ogata N, Akune T, Kubota N, Yamauchi T, Terauchi Y, Kadowaki T, Takeuchi Y, Fukumoto S, Ikeda T, Hoshi K, Chung UI,Nakamura K, Kawaguchi H. Regulation of boneformation by adiponectin through autocrine/
paracrine and endocrine pathways. J Cell Biochem
2006; 99: 196-208.
12) Susami T, Sugawara Y, Matsuzaki M, Ogihara Y,
Sakiyama M, Takato T, Matsumoto S. Segmental
alveolar distraction for the correction of unilateral
open-bite caused by multiple ankylosed teeth: Acase report. Journal of Orthodontics 2006; 33: 153159.
13) Susami T, Ogihara Y, Matsuzaki M, Sakiyama M,
Takato T, Shaw WC, Semb G. Assessment of dentalarch relationships in Japanese patients with unilat-

228

eral cleft lip and palate. Cleft Palate-Craniofacial J
2006; 43: 96-102.
14) Yanagi Y, Inoue Y, Kawase Y, Uchida S, Tamaki
Y, Araie M, Okochi H. Properties of growth andmolecular profiles of rat progenitor cells from ciliary epithelium. Exp Eye Res 2006; 82: 471-478.
15) Yamaoka H, Asato H, Ogasawara T, Nishizawa S,
Takahashi T, Nakatsuka T, Koshima I, Nakamura K,
Kawaguchi H, Chung UI, Takato T, Hoshi K.
Cartilage tissue engineering using human auricularchondrocytes embedded in different hydrogel materials. J Biomed Mater Res A 2006; 78A: 1-11.
16) Yamagami S, Mimura T, Yokoo S, Takato T, Amano S. Isolation of Human Corneal Endothelial Cell
Precursors and Construction of Cell Sheets by Precursors. Cornea 2006; 25: S90-S92.
17) Yamada T, Kawano H, Koshizuka Y, Fukuda T,
Yoshimura K, Kamekura S, Saito T, Ikeda T, Kawasaki Y, Azuma Y, Ikegawa S, Hoshi K, Chung UI,Nakamura K, Kato S, Kawaguchi H. Carminerin
contributes to chondrocyte calcification during endochondral ossification. Nat Med 2006; 12:665-670.
18) Yokoo S, Yamagami S, Mimura T, Amano S, Saijo
H, Mori Y, Takato T. UV absorption in human oral
mucosal epithelial sheets for ocular surface reconstruction. Ophthalmic Res 2006; 38: 350-354.

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Department ofOrthopaedic Surgery
Professor
Kozo Nakamura, M.D., Ph.D.

Associate Professors
Yoshio Takatori, M.D., Ph.D.,

Hiroshi Kawaguchi, M.D., Ph.D.

Lecturers
Isao Ohnishi, M.D., Ph.D.,

Atsushi Seichi, M.D., Ph.D.,

Sakae Tanaka, M.D., Ph.D.,

Katsushi Takeshita, M.D., Ph.D.

Associates
Motoi Yamamoto, M.D., Ph.D.,
Hirotaka Kawano, M.D., Ph.D.,
Ko Matsudaira, M.D., Ph.D.,
Hideya Itoh, M.D.,
Toru Akiyama, M.D., Ph.D.,
Nobuhiro Hara, M.D.,
Yusuke Shinoda M.D.,Ph.D.,

Homepage

Tatsuro Karita, M.D., Ph.D.,
Takumi Nakagawa, M.D., Ph.D.,
Toshiki Miura, M.D., Ph.D.
Yuho Kadono, M.D., Ph.D.
Yukinori Hara, M.D.,
Shuichi Nakayama, M.D.,
Hideki Takeda M.D.

http://www.h.u-tokyo.ac.jp/ortho/

Introduction and Organization
In 1906 our department was established as the firsteducational institute of orthopedic surgery in Japan, by
the first Professor Yoshinori Tashiro who had learned
orthopedic surgery in German and Austria. Hence, wecelebrate the centennial of the department this year.
Initially, the department treated patients with infectious disorders and congenital malformations, such aspoliomyelitis, tuberculosis of the spine, congenital
clubfoot and hip dislocation. The number of outpatients
visiting our department in 1910 was estimated to be no
more than 3.3% that of the two surgical departments in
the University of Tokyo Hospital.
The number and characteristics of the patients, however, have changed dramatically in these 100 years.
This is because our department addressed the acuteneeds of society from the beginning. Prof. Tashiro believed that trauma should be treated by orthopedists, so

he provided his pupils with this training. Since 1950’s,
the department has increasingly been involved in thetreatment of traffic and industrial accident victims. Prof.
Tashiro and his successor Professor Kenji Takagi devoted themselves to the establishment of an institute forchildren with disabilities. The arthroscope was developed by Prof. Takagi, and is now considered to represent a breakthrough in the development of minimallyinvasive surgery. We have recently been conducting
many studies related to the ossification of spinal ligaments (OPLL), rheumatoid arthritis, biomechanics, andthe degenerative skeletal disorders such as osteoporosis
and osteoarthritis in response to the progressive agingof our society.
Our department is now adept in the entire field of
medical science and medical practice related to the human motor system, the importance of which is now
clearly recognized not only in Japan, but also all over
the world. To meet the expanding needs of society, we230

have been conducting the teaching, clinical, and research activities described below.
Faculty members of the department are the top professor, two associate professors, four lecturers, 13 associates, 12 medical staff members, and 11 part-timeteachers.

Teaching activities
In undergraduate education, our department takes
part in systemic lectures, diagnostic lectures, and problem based learning (PBL) for 4th year medical students,
bedside learning and Clinical Clerkship for 5th year
medical students, and clinical lectures for 6th year
medical students.
Systemic lectures offer comprehensive presentation
for covering basic knowledge of the concept, pathogenesis, pathology, diagnosis and treatment of various
motor system disorders is performed. The 12 consecutive lectures cover bone and soft tissue tumors, spinal
diseases, joint diseases (hand, shoulder, elbow, hip,knee, and ankle), sports injuries, traumatology, andrheumatoid diseases. In the diagnostic lectures, weteach diagnostic maneuvers and radiological diagnosis
of a variety of skeletal diseases. PBL is offered to asmall group work to learn medical humanity and systematic methods to develop medical research.
During the 10-day period of bed-side learning, students have opportunities to experience daily clinicalcare with residents as well as practicing with faculty
members. We have developed an original text for the
students to learn orthopedics effectively. They participate in clinical conferences and surgery, and make reports on diagnostic and therapeutic procedures. They
learn how to conduct a medical interview, check physical findings and draw up actual plans for a diagnosis
and treatment including surgery.
Clinical Clerkship provides 4 weeks of early exposure to the clinical practice. The students are attached toa clinical team and are involved in most of the clinicalactivities performed by the team.
In clinical lectures, we present the clinical aspects ofimportant skeletal diseases, and discuss with the students several points for reaching a diagnosis and planning a treatment. Osteoarthritis and metastatic bonetumors were focused on in 2005 and 2006, respectively.

For postgraduate education, junior residents join our
department for 5-8 months. Since the training period isshort, the residents are expected to experience emergency cases as often as possible. A postgraduate seminar and a basic research conference are held weekly.
Twelve basic orthopaedic seminars by invited guest
speakers were held in 2006.
Including the postgraduate training, a ten-year course
has been adopted with clinical and research training
taking place either in the University of Tokyo Hospitalor in our 50 affiliated hospitals.

Clinical activities
We have the outpatient clinic open from Monday
through Friday, with specialized divisions for spine, hip,rheumatoid arthritis, tumor, scoliosis, limb reconstruction and bone lengthening, knee, hand, elbow, shoulder,sports, peripheral nerves, and bone systemic disorders.
A total of 43,282 patients visited the outpatient clinic
from April 2005 through March 2006.
The ward has approximately 55 to 65 beds available
and is divided into the subgroups above. The members
are on duty for daily patient care under the supervisionof faculty members. The weekly official activities ofour department are ward rounds by the professor on
Tuesday. We have post- and preoperative case conferences on Monday evening, Tuesday morning andThursday evening.
Six hundred and thirty three operations were performed in 2006. These include 89 cervical and thoracic
spine surgeries (including 44 computer-assisted surgeries (CAS)), 54 lumbar spine surgeries, 12 scoliosis surgeries (including 12 CAS), 63 surgeries for rheumatoid
arthritis patients, 78 hip surgeries, 63 knee surgeries(including 19 CAS), 12 shoulder surgeries, 97 handsurgeries, 12 limb lengthening and reconstruction surgeries using external fixators, 71 surgeries for bone andsoft tissue tumor and 88 trauma surgeries.
The main disorders of cervical spine surgery weremyelopathy due to spondylosis or OPLL. We successfully adopted double-door open laminoplasty by splitting the spinal processes for most of these cases. This
procedure was invented and developed in our department and is now used nationwide. The present professor Kozo Nakamura has also been the chief investigatorof a national project to investigate OPLL. Difficult op-

231

erations such as subluxation of the cervical spine due torheumatoid arthritis, Down’s syndrome or cerebral palsy were treated using a navigation system that has been
officially approved as a high-level advanced medical
treatment.
The lumbar spine group developed a new posterior
decompression technique which preserves the spinous
processes and interspinous ligaments, and successfully
uses it for lumbar spinal canal stenosis. Randomized
clinical trials are now ongoing by this group.
Main operations performed by the rheumatoid arthritis clinic group were total joint arthroplasty. They areusing image-free navigation system in total knee arthroplasty operation, which is useful for the accurate
placement of the implants.
The hip surgery group treated mainly acetabular dysplasia and osteoarthritis of the hip joint. They performed not only total hip replacements, but also several
osteotomies including rotational acetabular osteotomy(RAO). The RAO was originated and established in our
department. They are now developing a long-life artificial joint using the MPC polymer in collaboration with
the Department of Materials Engineering in Tokyo
University.
The knee clinic group developed a new endoscopic
anterior cruciate ligament reconstruction technique using the navigation system based on fluoroscopic images
to realize ideal graft placement.
The peripheral nerve clinic group has developed"costal nerve transfer to the musculocutaneous nerve"
for brachial plexus injury.
Limb reconstruction operations using external fixators included non-union, leg lengthening and deformity
correction. One of the main interests of this group is thedevelopment of a system to analyze the mechanicalproperties of a skeletal system. During this period ofanalysis, the mechanical properties of the fracture site
in vivo are to be evaluated by monitoring the motion ofa dynamic pin clamp during simulated walking.

Research activities
Our research activities cover the full range of the
motor system medicine, using the in-depth sciences of
biology and technology. Especially in the field of molecular biology of bone and cartilage metabolism, weare regarded as being on the leading edge in the world.

Basic research is performed under the supervision of
the faculty staff members. The main research topics wehave focused on are as follows.
1) Molecular backgrounds of bone and joint diseases
using forward and reverse genetics approaches
2) Signaling of differentiation and apoptosis of osteoclasts
3) Etiology of OPLL
4) Molecular background underlying the joint destruction by rheumatoid arthritis
5) Molecular background of osteoarthritis using amouse genomics approach6) Non-invasive evaluation of bone strength using afinite elementary measurement
7) In vivo bone formation by cytokines and its clinicalapplication
8) Molecular mechanism of age-related bone and cartilage disorders
In addition to the activities inside the department, wehave established two endowment departments in the22th Century Medical Center that deal with clinical research, which houses the largest clinical database of
osteoarthritis patients in the world for the pursue ofgenomic and etiological research. Another endowment
department is in the Division of Tissue Engineering,which seeks to aims develop epochal bone and cartilage
regenerative medicine. Furthermore, we collaborate
with the Center for Disease Biology and Integrative
Medicine (CDBIM), and are developing nonviral genedelivery vectors (polyion complex micelles) andlong-life artificial joints for clinical application in thenear future.

References
1.

2.

3.

Anamizu Y, Seichi A, Tsuzuki N, Nakamura K.
Age-related changes in histogram pattern of anterior horn cells in human cervical spinal cord.
Neuropathology 2006; 26: 533-539.
Fukui N, Ikeda Y, Ohnuki T, Hikita A, Tanaka S,
Yamane S, Suzuki R, Sandell JL, Ochi T.
Pro-inflammatory cytokine TNF-alpha induces
BMP-2 in chondrocytes via mRNA stabilizationand transcriptional up-regulation. J Biol Chem
2006; 281:27229-27241
Hikita A, Yana I, Wakeyama H, Nakamura M,
Kadono Y, Oshima Y, Nakamura K, Seiki M, Ta-232naka S. Negative regulation of osteoclastogenesis
by ectodomain shedding of receptor activator of
NF-kappaB ligand. J Biol Chem 2006; 281:
36846-36855.
4. Hiraki S, Nakamura I, Okazaki H, Nakamura K,
Kurokawa T. Skin behavior during leg lengthening
in patients with achondroplasia and hypochondroplasia: a short-term observation during leg
lengthening. J Orthop Sci 2006; 11: 267-271.
5. Hiraoka H, Kuribayashi S, Fukuda A, Fukui N,
Nakamura K. Endoscopic anterior cruciate ligament reconstruction using a computer-assisted
fluoroscopic navigation system. J Orthop Sci
2006; 11: 159-166.
6. Horikoshi T, Maeda K, Kawaguchi Y, Chiba K,
Mori K, Koshizuka Y, Hirabayashi S, Sugimori K,
Matsumoto M, Kawaguchi H, Takahashi M, Inoue
H, Kimura T, Matsusue Y, Inoue I, Baba H, Nakamura K, Ikegawa S. A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine. Hum Genet 2006;
119: 611-616.
7. Hoshikawa A, Nakayama Y, Matsuda T, Oda H,
Nakamura K, Mabuchi K . Encapsulation of chondrocytes in photopolymerizable styrenated gelatinfor cartilage tissue engineering. Tissue Eng 2006;
12: 2333-2341.
8. Imai K, Ohnishi I, Bessho M, Nakamura K. Nonlinear finite element model predicts vertebral bonestrength and fracture site. Spine 2006; 31:1789-94
9. Kamekura S, Kawasaki Y, Hoshi K, Shimoaka T,
Chikuda H, Maruyama Z, Komori T, Sato S, Takeda S, Karsenty G, Nakamura K, Chung UI, Kawaguchi H. Contribution of runt-related transcription factor 2 to the pathogenesis of osteoarthritis inmice after induction of knee joint instability.
Runx2 contributes to pathogenesis of osteoarthritis
in mice after induction of knee joint instability.
Arthritis Rheum 2006; 54: 2462-2470
10. Katagiri M, Ogasawara T, Hoshi K, Chikazu D,
Kimoto A, Noguchi M, Sasamata M, Harada S,
Akama H, Tazaki H, Chung UI, Takato T, Nakamura K, Kawaguchi H. Suppression of adjuvant-induced arthritic bone destruction by cyclooxygenase-2 selective agents with and without
inhibitory potency against carbonic anhydrase II. J
Bone Miner Res 2006; 21: 219-227.

11. Kawaguchi H, Akune T, Ogata N, Seichi A, Takeshita K, and Nakamura K: Contribution of metabolic conditions to ossification of the posterior
longitudinal ligament of the spine. in "OPLL - Ossification of the Posterior Longitudinal Ligament –2nd Edition". edited by K. Yonenobu, T. Nakamura, and Y. Toyama. 2006 (Springer-Verlag Tokyo): 37-40
12. Kawaguchi H. Molecular backgrounds of agerelated osteoporosis from mouse genetics approaches. Rev Endocr Metab Disord 2006; 7:
17-22.
13. Koshizuka Y, Ogata N, Shiraki M, Hosoi T, Seichi
A, Takeshita K, Nakamura K, and Kawaguchi H:
Distinct association of gene polymorphisms of estrogen receptor and vitamin D receptor with lumbar spondylosis in postmenopausal women. Eur
Spine J 2006; 15: 1521-1528.
14. Koyama Y, Miyashita M, Kazuma K, Suzukamo
Y, Yamamoto M, Karita T, Takatori Y. Preparing
a version of the Nottingham adjustment scale (forpsychological adjustment) tailored to osteoarthritisof the hip. J Orthop Sci 2006; 11: 359-64.
15. Kugimiya F, Ohba S, Nakamura K, Kawaguchi H,
Chung UI. Physiological role of bone morphogenetic proteins in osteogenesis. J Bone Miner Metab 2006; 24: 95-99.
16. Mabuchi A, Nakamura S, Takatori Y, Ikegawa S.
Familial osteoarthritis of the hip joint associatedwith acetabular dysplasia maps to chromosome
13q. Am J Human Genet 2006; 79: 163-168.
17. Maruyama T, Kitagawa T, Takeshita K, Seichi A,
Kojima T, Nakamura, Kurokawa T. Fusionless
surgery for scoliosis: 2-17 year radiographic andclinical follow-up. Spine 2006; 31: 2310-2315.
18. Maruyama T, Takeshita K, Seichi A, Kitagawa T,
Kojima T, Nakamura K, Kurokawa T. Multiple
vertebral wedge osteotomy for adolescent idiopathic scoliosis. Stud Health Technol Inform
2006; 123: 283-8.
19. Matsuyama J, Ohnishi I, Sakai R, Suzuki H, Harada A, Bessho M, Matsumoto T, Nakamura K. A
new method for measurement of bone deformationby echo tracking. Med Eng Phys 2006; 28:588-595.

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20. Miyazaki T, Tanaka S, Sanjay A, Baron R. The
role of c-Src kinase in the regulation of osteoclast
function. Mod Rheumatol 2006; 16:68-74.
21. Moro T, Takatori Y, Ishihara K, Nakamura K,
Kawaguchi H. Grafting of biocompatible polymer
for longevity of artificial hip joints. Clin Orthop
Rel Res 2006; 453: 58-63.
22. Muraki S, Yamamoto S, Ishibashi H, Nakamura K.
Factors associated with mortality following hip
fracture in Japan. J Bone Miner Metab 2006;
24:100-4.
23. Nakagawa T, Hiraoka H, Fukuda A, Matsubara T,
Nakayama S, Nakamura K. Symptomatic cyclops
lesion after rupture of the anteromedial bundle of
the anterior cruciate ligament. J Orthop Sci 11:
537-540, 2006
24. Nakamura K. Professor Yoshinori Tashiro's contribution to orthopedic surgery. J Orthop Sci
2006; 11: 115-117.
25. Oda H, Nakamura K, Matsushita T, Yamamoto S,
Ishibashi H, Yamazaki T, Morimoto S. Clinicaluse of a newly developed calcium phosphate cement (XSB-671D). J Orthop Sci 2006; 11:167-174.
26. Ogata T, Yamamoto S, Nakamura K and Tanaka S.
Signaling Axis in Proliferation and Differentiationof Schwann Cell. Mol Neurobiol. 2006; 33:51-62.
27. Ogihara S, Seichi A, Hozumi T, Oka H, Ieki R,
Nakamura K, Kondoh T. Prognostic factors forpatients with spinal metastases from lung cancer.
Spine 2006; 31:1585-1590.
28. Ohori Y, Yamamoto S, Nagao M, Sugimori M,
Yamamoto N, Nakamura K, Nakafuku M. Growth
factor treatment and genetic manipulation stimulate neurogenesis and oligodendrogenesis by endogenous neural progenitors in the injured adultspinal cord. J Neurosci 2006; 26: 11948-11960.
29. Oka H, Kondoh T, Seichi A, Hozumi T, Nakamura
K. Incidence and prognostic factors of Japanese
breast cancer patients with bone metastasis. J Orthop Sci 2006, 11: 13-19
30. Oka H, Yoshimura N, Kinoshita H, Saiga A, Kawaguchi H, Nakamura K. Decreased activities ofdaily living and associations with bone loss among
aged residents in a rural Japanese community: theMiyama Study. J Bone Miner Metab 2006; 24:
307-313.

31. Oshima Y, Okutsu I, Hamanaka I, Motomura T.
Carpal tunnel syndrome accompanying radial dysplasia due to thalidomide embryopathy. J Hand
Surg [Br] 2006; 31 :342-344.
32. Saito T, Kondo T, Hozumi T, Karasawa k, Seichi
A, Nakamura K: Results of posterior surgery withintraoperative radiotherapy for spinal metastases.
Eur Spine J 2006, 15: 216-222.
33. Sakanishi H, Hoshi K, Nakajima S, Akune T, Takeshita K, Yamamoto M, Kawaguchi H, Nakamura K, Seichi A. Vertebral hemangioma
compressing the thoracic spinal cord. J Orthop Sci
2006; 11: 294-297.
34. Sato K, Suematsu A, Okamoto K, Yamaguchi A,
Morishita Y, Kadono Y, Tanaka S, Kodama T,
Akira S, Iwakura Y, Cua DJ, Takayanagi H. Th17
functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction.
J Exp Med 2006; 203:2673-2682.
35. Sawada Y, Tamada M, Dubin-Thaler BJ, Cherniavskaya O, Sakai R, Tanaka S, Sheetz MP.
Force Sensing by Mechanical Extension of the Src
Family Kinase Substrate p130Cas. Cell 2006;
127:1015-1026.
36. Seichi A, Takeshita K, Kawaguchi H, Matsudaira
K, Higashikawa A, Ogata N, Nakamura K. Neurologic level diagnosis of cervical stenotic myelopathy. Spine 2006; 31: 1338-1343.
37. Shinoda Y, Yamaguchi M, Ogata N, Akune T,
Kubota N, Yamauchi T, Terauchi Y, Kadowaki T,
Takeuchi Y, Fukumoto S, Ikeda T, Hoshi K,
Chung UI, Nakamura K, Kawaguchi H. Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways. J Cell
Biochem 2006; 196-208.
38. Takeshita K, Lenke L, Bridwell K, Kim YJ, Sides
B, Hensley M. Analysis of patients with nonambulatory neuromuscular scoliosis patients surgically treated to the pelvis with intraoperative Halo-femoral traction. Spine 2006; 31: 2381-5.
39. Takeshita K, Maruyama T, Matsudaira K, Murakami M, Higashikawa A, Nakamura K. Validity
and reliability of SRSI and SF-36 in Japanese patients with scoliosis. Stud Health Technol Inform.
2006; 123: 337-42.
40. Takeshita K, Maruyama T, Murakami M, Higashikawa A, Hashimoto H, Hara N, Seichi A. Na-

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41.

42.

43.

44.

45.

46.

kamura K. Correction of scoliosis using segmental
pedicle screw instrumentation versus hybrid constructs with hooks and screws. Res Spinal Deform
2006; 5: 571-573.
Takeshita K, Maruyama T, Murakami M, Higashikawa A, Hashimoto H, Hara N, Seichi A, Nakamura K. Correction of scoliosis using segmental
pedicle screw instrumentation versus hybrid constructs with hooks and screws. Stud HealthTechnol Inform 2006; 123: 571-6.
Tanaka S, Miyazaki T, Fukuda A, Akiyama T, Kadono Y, Wakeyama H, Kono S, Hoshikawa S, Nakamura M, Ohshima Y, Hikita A, Nakamura K.
Molecular mechanism of the life and death of theosteoclast. Ann N Y Acad Sci 2006; 1068:180186.
Tanaka S, Suzuki H, Yamauchi H, Nakamura I and
Nakamura K. Signal transduction pathways of calcitonin/calcitonin receptor regulating cytoskeletalorganization and bone-resorbing activity of osteoclasts. Cell Mol Biol 2006; 52: 19-23.
Yamada T, Kawano H, Koshizuka Y, Fukuda T,
Yoshimura K, Kamekura S, Saito T, Ikeda T, Kawasaki Y, Azuma Y, Ikegawa S, Hoshi K, Chung
UI, Nakamura K, Kato S, and Kawaguchi H: Carminerin contributes to chondrocyte calcification
during endochondral ossification. Nature Med 12:665-670, 2006.
Yamaoka H, Asato H, Ogasawara T, Nishizawa S,
Takahashi T, Nakatsuka T, Koshima I, Nakamura
K, Kawaguchi H, Chung UI, Takato T, Hoshi K.
Cartilage tissue engineering using human auricularchondrocytes embedded in different hydrogel materials. J Biomed Mater Res A 2006; 78: 1-11.
Yoshimura N, Kinoshita H, Hori N, Nishioka T,
Ryujin M, Mantani Y, Miyake M, Takeshita T,
Ichinose M, Yoshida M, Oka H, Kawaguchi H,
Nakamura K, Cooper C. Risk factors for knee osteoarthritis in Japanese men: A case control study.
Mod Rheumatol 2006; 16(1): 24-29.

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Department of Ophthalmology
Professor
Makoto Araie, M.D., Ph.D.

Associate Professor
Satoru Kato, M.D., Ph.D.,

Yasuhiko Tamaki, M.D., Ph.D.

Lecturer
Makoto Aihara, M.D., Ph.D.,
Miyuki Nagahara, M.D., Ph.D.,
Ryuichi Ideta, M.D

Atsushi Tomidokoro, M.D., Ph.D.,
Toshikatsu Kaburaki, M.D., Ph.D,

Associate
Tomohiko Usui, M.D., Ph.D.,
Yasuo Noda, M.D., Ph.D.,
Koichi Mishima, M.D., Ph.D.,
Takashi Shigeeda, M.D.,
Kenji Sugisaki, M.D.,
Shinsuke Konno, M.D., Ph.D.

Homepage

Yasuo Yanagi, M.D., Ph.D.,
Yuji Inoue, M.D., Ph.D.,
Keiko Hayashi, M.D.,
Akira Hirose, M.D.,
Takuya Atarashi, M.D.,
Tatsuya Mimura, M.D., Ph.D.

http://plaza.umin.ac.jp/ophl

Introduction and Organization
The Department of Ophthalmology, University ofTokyo School of Medicine, was founded in 1989. Since
then, the department has contributed to Japanese ophthalmology not only by educating a large number ofeminent ophthalmologists in Japan, but also by producing significant basic research in ophthalmology.
The department has been active in collaboration with
ophthalmologists around the world, sponsoring international ophthalmological meetings, educating fellows
from foreign countries and sending our staff and fellows abroad.

Clinical activities
Altogether, approximately 5000 new outpatients areseen every year in our hospital, which has a total of 44
beds. Residents work in the ambulatory section andtake care of inpatients. Special services are provided inunits devoted to ophthalmic subspecialities such as

cornea, glaucoma, retina, uveitis, neuro-ophthalmology,
orthoptics, diabetic retinopathy, and genetic and color
blindness problems. The staff members supervise theambulatory and special services depending on each
one’s speciality.
Most of the inpatients suffer from cataract, glaucoma,
corneal diseases, retinal detachment, diabetic retinopathy, uveitis and strabismus. Surgeries are performed in
the operating theater of the hospital under operating
microscopes. Approximately 2000 cases underwent
operations in our department. Surgeries can be monitored by TV system which is mounted on operating microscopes. Since multiple observers can watch the sameimages and share findings, this system has a great potential in training and promoting discussion.

Teaching activities
As an undergraduate course, we give lectures on
corneal physiology, corneal diseases, and corneal transplantation. In addition, we are engaged in practical

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training for medical students on ophthalmological examinations at the outpatient clinic. As a postgraduate
course, we give lectures on topics concerning corneal
transplantation, corneal diseases and new medical therapies.

Research activities
Research topics in our department cover a variety offields in ophthalmology; e.g. ocular pharmacology, regenerative medicine in the cornea and retina, aqueous
humour dynamics, immunology and molecular biology.
Special laboratories for physiology, pharmacology andgenetic engineering have been established. Specificfields of research in our department are as follows.
1. Analysis with laser-speckle method of vascularflow in retina and iris
2. Clinical investigation of normal tension glaucoma
3. Analysis of dynamics of aqueous flow
4. Drug effect on glaucoma
5. Screening method of glaucoma
6. Tissue engineering of the cornea
7. Clinical investigation of corneal shape
8. Gene therapy in corneal transplantation
9. Role of advanced glycation endproducts in oculardiseases
10. Clinical and basic research of excimer laser refractive surgery
11. Molecular analysis of retinal degenerative diseases
12. Color blindness and visual function
13. Electrophysiological analysis of the effect of drugs
on the retina
14. Biocompatibility of intraocular lenses
15. Immuno-hereditary analysis of Harada’s disease
and Bechet’s disease
16. Immunosuppressive reagents on Bechet’s disease
17. Pathophysiology and molecular mechanisms of
diabetic retinopahty

References
1.

2.

Akiyama K, Numaga J, Kawashima H, Kaburaki T
and Yoshida A, Fujino Y: Statistical analysis of
Endogenous Uveitis at Tokyo University Hospital(1998-2000). Jpn J Ophthalmol 50:69-71, 2006
Amano S, Fukuoka S, Usui T, Honda N, Ideta R,
Ochiai M, Yamagami S, Araie M, Awaya

Y :Ocular manifestation of congenital insensitivity
to pain with anhidrosis. Am J Ophthalmol 141:472-477, 2006
3. Amano S, Honda N, Amano Y, Yamagami S, Miyai
T, Samejima T, Ogata M, Miyata K :Comparisonof central corneal thickness measurements by rotating Scheimpflug camera, ultrasonic pachymetry,and scanning-slit corneal topography. Ophthalmology 113:937-941, 2006
4. Amano S, Yamagami S, Mimura T, Uchida S, Yokoo S: Corneal stromal and endothelial cell precursors. Proceedings of the Eleventh Annual
Meeting of the Kyoto Cornea Club, Cornea 25:7377, 2006
5. Ebihara Y, Kato S, Oshika T, Yoshizaki M, Sugita
G: Posterior capsule opacification after cataract
surgery in patients with diabetes mellitus. J Cataract Refract Surg 32:1184-1187, 2006
6. Enomoto K, Mimura T, Harris DL, Joyce NC: Age
differences in cyclin-dependent kinase inhibitor
expression and rb hyperphosphorylation in humancorneal endothelial cells. Invest Ophthalmol Vis
Sci 47:4330-40, 2006
7. Funatsu H, Yamashita H, Nakamura S, Mimura T,
Eguchi S, Noma H, Hori S. Vitreous levels of
pigment epithelium-derived factor and vascularendothelial growth factor are related to diabetic
macular edema. Ophthalmology 113:294-301,
2006
8. Hamada N, Kaiya T, Oshika T, Kato S, Tomita G,
Yamagami S, Amano S: Optic disc and retinal
nerve fiber layer analysis with scanning laser tomography after laser in situ keratomileusis. J Refract Surg 22:372-375, 2006
9. Inoue T, Terada K, Furukawa A, Koike C, Tamaki
Y, Araie M, Furukawa T :Cloning and characterization of mr-s, a novel SAM domain protein, predominantly expressed in retinal photoreceptor cells.
BMC Developmental Biology 6:15, 2006.
10. Iwase A, Araie M, Tomidokoro A, Yamamoto T,
Shimizu H, Kitazawa Y; Tajimi Study Group.
Prevalence and causes of low vision and blindness
in a Japanese adult population: the Tajimi Study.
Ophthalmology 113:1354-62, 2006
11. Jin, Z. B., Ito S, Saito Y, InoueY, Yanagi Y, Nao-i
N :Clinical and molecular findings in three Japanese patients with crystalline retinopathy. Jpn J

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Ophthalmol 50: 426-31, 2006
Kadonosono K, Kamezawa H, Uchio E, Tamaki Y,
Araie M: Bimanual vitreous surgery with slit-beamillumination and a multicoated contact lens. Retina
26:708-709, 2006
Kadonosono K, Yamakawa T, Uchio E, Yanagi Y,
Tamaki Y, Araie M: Comparison of visual function after epiretinal membrane removal by
20-gauge and 25-gauge vitrectomy. Am J Ophthalmol 142: 513-515, 2006
Kawano J, Tomidokoro A, Mayama C, Kunimatsu
S, Tomita G, Araie M: Correlation between hemifield visual field damage and corresponding parapapillary atrophy in normal-tension glaucoma. Am
J Ophthalmol 142:40-45, 2006
Kawasaki S, Hasegawa O, Satoh S, Saito T, Ishio
H, Fukushima H, Kato S, Yamashita H, Terauchi Y,
Sekihara H: Development and progression of retinopathy after inpatient management of diabetes.
Internal Medicine 45:1267-1271, 2006
Kinouchi R, Kinouchi T, Hamamoto T, Saito T,
Tavares A, Tsuru T, Yamagami S. Distribution of
CESP-1 protein in the corneal endothelium andother tissues. Invest Ophthalmol Vis Sci 47:13971403, 2006
Kunimatsu S, Mayama C, Tomidokoro A, Araie
M: Plasma endothelin-1 level in Japanese normal
tension glaucoma patients. Curr Eye Res 31:727731, 2006
Kunimatsu S, Tomidokoro A, Saito H, Aihara M,
Tomita G, Araie M: Performance of GDx VCC ineyes with peripapillary atrophy: comparison of
three circle sizes Eye. 2006 Aug 4; [Epub ahead ofprint]
Kurita N, Tomidokoro A, Mayama C, Aihara M,
Araie M: No apparent association between ocular
perfusion pressure and visual field damage innormal-tension glaucoma patients. Jpn J Ophthalmol 50:547-549, 2006
Mimura T, Funatsu H, Usui T, Yamagami S, Noma H, Amano S: Topical ocular drug delivery to
inner ear disease and sinusitis. Southern Medical
Journal 99: 1287-1289, 2006
Mimura T, Joyce NC: Replication competence andsenescence in central and peripheral human corneal endothelium. Invest Ophthalmol Vis Sci
47:1387-1396,2006

22. Wang M, Yoshida A, Kawashima H, Takahashi H,
Hori J: Immunogenicity and antigenicity of allogeneic amniotic epithelial transplants grafted tothe cornea, conjunctiva, and anterior chamber. Invest Opthalmol Vis Sci 47:1522-1532, 2006
23. Miyata K, Otani S, Miyai T, Nejima R, Amano S:
Atelocollagen punctal occlusion in dry eye patients. Cornea 25:47-50, 2006
24. Muranaka K, Yanagi Y, Tamaki Y, Usui T, Ohashi K, Matsuoka H, Senda T : Ef fects of peroxisome proliferator-activated receptor gamma andits ligand in on b lood retinal barrier instreptozotocin-induced diabetic model. Invest
Ophthalmol Vis Sci 47: 4547-4552, 2006
25. Nejima R, Miyai T, Kataoka Y, Miyata K, Honbou
M, Tokunaga T, Kawana K, Kiuchi T,Tetsuro
Oshika:Prospective Intrapatient Comparison of
6.0-Millimeter Optic Single-Piece and 3-Piece
Hydrophobic Acrylic Foldable Intraocular Lenses.
Ophthalmology 113:585-590, 2006
26. Noma H, Funatsu H, Yamasaki M, Tsukamoto H,
Mimura T, Sone T, Hirayama T, Tamura H, Yamashita H, Minamoto A, Mishima HK: Aqueous humour levels of cytokines are correlated to vitreouslevels and severity of macular oedema in branchretinal vein occlusion. Eye Jul 7; [Epub ahead ofprint] 2006
27. Obata R, Yanagi, Y, Tamaki Y : Postoperative
assessment of retinal function using a multifocal
electroretinogram after the removal of subfoveal
choroidal neovascularization secondary to agerelated macular degeneration. Jpn J Ophthalmol
50: 479-82, 2006
28. Obata R, Yanagi Y, Iriyama A, Tamaki Y: A familial case of pigmented paravenous retinochoroidal
atrophy with asymmetrical fundus manifestations.
Graefes Arch Clin Exp Ophthalmol 244:874-877,
2006
29. Obata R, Yanagi Y, Kami J, Takahashi H, Inoue Y,
Tamaki Y : Polypoidal choroidal vasculopathy andretinochoroidal anastomosis in Japanese patients
eligible for photodynamic therapy of exudative
age-related macular degeneration. Jpn J Ophthalmol 50:354-360, 2006
30. Obata R, Yanagi Y, Tamaki Y. Postoperative assessment of retinal function using a multifocal
electroretinogram after the removal of subfoveal

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choroidal neovascularization secondary to
age-related macular degeneration. Jpn J Ophthalmol 50:479-482, 2006
Ohara K, Kato S, Hori S, Kitano S: Tilt and decentration of the intraocular lens following combined vitrectomy and pars plana lensectomy. Acta
Ophthalmol Scand 84:388-389, 2006
Osakabe Y, Yaguchi C, Miyai T, Miyata K, Mineo S, Nakamura M, Amano S : Detection of
streptococcus species by polymerase chain reaction in infectious crystalline keratopathy. Cornea
25:1227-1230, 2006
Oshika T, Tokunaga T, Samejima T, Miyata K,
Kawana K, Kaji Y: Influence of pupil diameter on
the relation between ocular higher-order aberrationand contrast sensitivity after laser in situ keratomileusis Invest Ophthalmol Vis Sci 47:13341338, 2006
Oshika T, Okamoto C, Samejima T, Tokunaga T,
Miyata K: Contrast sensitivity function and ocularhiher-order wavefront aberrations in normal human eyes. Ophthalmology 113:1807-1812, 2006
Ota T, Aihara M, Narumiya S, Araie M: The Effects of Prostaglandin Analogues on Prostanoid
EP1, EP2, and EP3 Receptor-Deficient Mice. Invest Ophthalmol Vis Sci 47:3395-3399, 2006
Read RW, Yu F, Accorinti M, Bodaghi B, Chee SP,
Fardeau C, Goto H, Holland GN, Kawashima H,
Kojima E, Lehoang P, Lemaitre C, Okada AA, Pivetti-Pezzi P, Secchi A, See RF, Tabbara KF, Usui
M, Rao NA: Evaluation of the effect on outcomesof the route of administration of corticosteroids inacute Vogt-Koyanagi-Harada disease. Am J Ophthalmol 142:119-124, 2006
Saito H, Tomidokoro A, Sugimoto E, Aihara M,
Tomita G, Fujie K, Wakakura M, Araie M: Optic
disc topography and peripapillary retinal nerve fiber layer thickness in nonarteritic ischemic optic
neuropathy and open-angle glaucoma. Ophthalmology 113:1340-1344, 2006
Sato K, Egami A, Odake T, Tokeshi M, Aihara M,
Kitamori T: Monitoring of intercellular messengers released from neuron networks cultured in a
microchip. J Chromatogr A 14;1111:228-232,2006
Sawa M, Tamaki Y, Klancnik JMJr, Yannuzzi LA:
Intraretinal foveal neovascularization in choroidelemia. Retina 26:585-588, 2006

40. Shigeeda T, Tomidokoro A, Chen YN, Shirato S,
Araie M: Long-term follow-up of initial trabeculectomy with mitomycin C for primary openangle glaucoma in Japanese patients. J Glaucoma
15:195-199, 2006
41. Shiraya T, Kato S, Fukushima H, Tanabe T: A caseof diabetic retinopathy with both retinal neovascularization and complete posterior vitreous detachment. Eur J Ophthalmol 16:644-646, 2006
42. Sugimoto EI, Aihara M, Ota T, Araie M. Effect oflight cycle on 24-hour pattern of mouse intraocularpressure. J Glaucoma 15:505-511, 2006
43. Suto C, Hori S, Kato S, Muraoka K, Kitano S: Effect of perioperative glycemic control in progression of diabetic retinopathy and maculapathy. Arch
Ophthalmol 124:38-45, 2006
44. Takahashi H, Obata R, Tamaki Y: A novel KDR
inhibitor,
SU11248
suppresses
choroidal
neovascularization in vivo. J Ocul Pharma Thera
22:213-218, 2006
45. Yamada H, Chen YN, Aihara M, Araie M. Neuroprotective effect of calcium channel blocker
against retinal ganglion cell damage under hypoxia.
Brain Res 1071:75-80, 2006
46. Yamagami S, Mimura T, Yokoo S, Takato T,
Amano S: Isolation of human corneal precursors
and construction of cell sheets by precursors. Proceedings of the Eleventh Annual Meeting of the
Kyoto Cornea Club, Cornea 25:90-92, 2006
47. Yamagami S, Ebihara N, Usui T, Yokoo S, Amano
S: Bone marrow-derived cells in normal humancorneal stroma. Arch Ophthalmol 124:62-69, 2006
48. Yanagi Y, Eguchi R, Obata R, Kami J, Tamaki
Y: Autoimmune retinopathy after chronic renal
allograft rejection. Arch Ophthalmol 124:418-420,
2006
49. Yanagi Y, Inoue Y, Kawase Y, Uchida S, Tamaki
Y, Araie M, Okochi H: Properties of growth andmolecular profiles of rat progenitor cells from ciliary epithelium. Exp Eye Res 82: 471-478, 2006
50. Yanagi Y, Inoue Y, Jang WD, Kadonosono K:
A2e mediated phototoxic effects of endoilluminators. Br J Ophthalmol 90: 229-232, 2006
51. Yanagi Y, Inoue Y, Iriyama A, Jang WD: Effectsof yellow intraocular lenses on light-induced
upregulation of vascular endothelial growth factor.
J Cataract Refract Surg 32:1540-1544, 2006

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52. Yokoo S, Yamagami S, Mimura T, Ono K, Amano
S, Saijo H, Mori Y, Takato T : UV-absorption inhuman oral mucosal epithelial sheets for ocularsurface reconstruction. Ophthalmic Res 38:350354, 2006
53. Yukawa E,Urano T, Nakahara M, Miyata K, Matsuura T, Taketani F, Hara Y, Mochizuki M: Pattern-reversal visual evoked potentials in patientswith human T-lymphotropic virus type 1 uveitis.
Curr Eye Res 31:37-42, 2006

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Department ofOtorhinolaryngology andHead & Neck Surgery
Professor
Tatsuya Yamasoba, M.D, Ph.D.

Lecturer
Ken Ito, M.D.,Ph.D,

Takahiro Asakage, M.D.,Ph.D,

Kazunari Nakao, M.D, Ph.D

Shinichi Iwasaki, M.D., Ph.D

AssociateKenji Kondo, M.D, Ph.D,
Shotaro Karino, M.D, Ph.D,
Miwako Kimura, M.D,
Muneo Nakaya, M.D, Ph.D,
Yasuhiro Chirara, M.D.,
Akinori Kashio, M.D,

Homepage

Takaharu Nito, M.D,
Yasuhiro Ebihara, M.D,
Kenta Watanabe, M.D,
Miho Hagisawa, M.D,
Keigo Suzukawa, M.D.,
Kae Kanaya, M.D.

http://www.h.u-tokyo.ac.jp/orl /Introduction and Organization
The Department of Otorhinolaryngology was
founded in 1899 by Prof.Waichiro Okada who studiedin Germany. This is the first department of otorhinolaryngology of the national university in Japan. It has
passed 107 years. Our department covers all otorhinolaryngological diseases and associated systemic diseases, and has specialized clinics in middle ear andinner ear diseases, hearing impaired infant and children,
adult and elderly patients, facial paresis, vertigo andbalance disorders, olfactory disorders and paranasal
diseases, voice and speech disorders, taste andswallowing respiratory disorders, aphasia, central
auditory disorders and head & neck cancers.
A professor, four lecturers (assistant professors) and
12 associates participate in surgery, out-patient andin-patient care as well as research and educational activities. One assistant professor is abroad at present forbasic and clinical research in the U.S.A. Moreover eight
Japanese graduate students and one Chinese foreign
graduate student participate in basic research.
Weekly preoperative and postoperative conferences
are held to discuss surgical cases in detail. Special lectures on leading research activities are presented byinvited guests on a regular basis. A weekly journal clubis held to introduce current research papers.

Clinical activities
In the out-patient clinic, general and special services
are provided to approximately 150 out-patients on adaily basis in all areas of otorhinolaryngology and related specialties, and approximately 400 new patients
visit monthly.
In the new inpatient hospital, 44 beds are preparedfor patients under the supervision of lecturers and senior residents from each subspecialty group including

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head & neck surgery, middle ear surgery and cochlear
implant surgery; voice and bronchoesophagologicalsurgery, and paranasal surgery and other minor surgery.
Peroperative and postoperative problems are checkedand discussed by each group, the professor’s and associate professor’s rounds. Approximately 650 operations
are performed annually.
Cochlear implant surgery over 140 cases has been
actively performed for infants, children and adult patients with profound hearing loss and is very successful
to provide new hearing. Head and neck surgery is performed to extirpate malignant tumor with neighboring
tissues and reconstruct upper respiratory and swallowing functions at one stage operation cooperating withplastic surgeons. Reconstructive surgery of microtia andatresia to reconstruct external ear is routinely performed
with plastic surgeons.
Auditory brainstem response is routinely examinedin order to diagnose peripheral and central deafness inneonates, infants and children.
Treatment of acoustic tumor using an ɤ-knife andauditory brainstem implant are performed in consultation with neurosurgons.

Teaching activities
For the fourth year medical students’ serial lecturesand for the fifth and sixth year medical students special
lectures on current topics are provided by the professor
and associate professor.
Clinical training is provided for the sixth year classof medical students on a one-to-one basis with staff
doctors. They are requested to write reports on a clinical case or a clinical problem. The students participate
to see surgery, special clinics and clinical examinations
such as otoscope, fiberscope, auditory brainstem response, and caloric test. Interview with patient is encouraged. They are questioned many aspects of clinicalproblems in seminars by professor and associate professor. During half and a week period, the students participate in surgery special clinics and practice of clinic
examination such otoscope, fiberscope auditory brainstem, caloric test and so on.

Research activities
Clinical and basic research activities are highly en-

couraged. Clinical research, which is supervised bysenior doctors, is very actively pursued even by young
residents. Case reports presentation and writing skills
are regarded as important experience in order to develop young doctors’ research activity and investigate
important findings in patients. The clinical research isrelated to ear surgery, neurotology, audiology, head &neck surgery, bronchoesophagology and rhinology andis related to case resersch, clinical statistics and clinicalelectrophysiology. Basic research is also encouraged tosolve essence of clinical problems and to elucidate basic phenomena or anatomical and cellular structures.
Our research topics cover:1) Morphology and neurophysiology of the inner ear
focusing on sensory neural deafness: human temporal bone pathology, electron microscopic study inanimal models, gene therapy.
2) Clinical application of otoacoustic emissions andauditory brainstem responses.
3) Histochemistry of olfactory epithelium in development and aging.
4) Clinical neurophysiology of the facial nerves focusing on degeneration and regeneration in patients.
5) Histochemistry of head and neck cancer pathology.
6) The central auditory corex research using MEG.
7) Auditory brainstem response and speech and hearing after the new born hearing screening.
8) Pathology and electrophysiology of the larynx.
9) Vestibular research on the oculomotor and balancesystems in the brain.
10) Vestibular myogenic evoked potentials in cochlear
implant and inner ear anomaly.
11) Hair cell physiology in the vestibular end organ.
12) Newborn hearing screening and language development in deaf childen.
13) Physiology bone conduction innovation of bone
conduction hearing and bilateral hearing.
14) Embryology of middle, inner ear and central auditory system.
Various clinical and basic research are conducted bystaffs, residents, postgraduate doctors and senior doctors at affiliated hospitals.

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References
1. Yamashita H, Nakagawa K, Nakamura N, Abe K,
Asakage T, Ohmoto M, Okada S, Matsumoto I,
Hosoi Y, Sasano N, Yamakawa S, Ohtomo K.
Re-lation between acute and late irradiation impair-ment of four basic tastes and irradiated tongue
volume in patients with head-and-neck cancer. Int J
Radiat Oncol Biol Phys 66:1422-9, 2006.
2. Fujimoto C, Ito K, Iwasaki S, Nakao K, Sugasawa
M. Reversible impairment of auditory callosal
pathway in 5-fluorouracil-induced leukoencephalopathy: parallel changes in function and imaging.
Otol Neurotol 27:716-9, 2006.
3. Hagisawa M, Yamasoba T, Ohashi K, Ishida T. A
case of middle-ear myoepithelioma. Otolaryngol
Head Neck Surg 135:967-8, 2006.
4. Iwasaki S, Ito K, Sugasawa M. Hypertrophic cranial pachymeningitis associated with middle ear inflammation. Otol Neurotol 27:928-33, 2006.
5. Karino S, Yumoto M, Itoh K, Uno A, Yamakawa K,
Sekimoto S, et al. Neuromagnetic responses tobinaural beat in human cerebral cortex. J Neurophysiol 96:1927-38, 2006.
6. Pawlowski KS, Kikkawa YS, Wright CG, Alagramam KN. Progression of inner ear pathology inAmes waltzer mice and the role of protocadherin
15 in hair cell development. J Assoc Res Otolaryngol 7:83-94, 2006.
7. Zheng QY, Yu H, Washington JL, 3rd, Kisley LB,
Kikkawa YS, Pawlowski KS, et al. A new spontaneous mutation in the mouse protocadherin 15 gene.
Hear Res 219:110-20, 2006.
8. Suzukawa M, Yamaguchi M, Komiya A, Kimura M,
Nito T, Yamamoto K. Ortho-phthalaldehydeinduced anaphylaxis after laryngoscopy. J Allergy
Clin Immunol 117:1500-1, 2006.
9. Murofushi T, Iwasaki S, Ushio M. Recovery ofvestibular evoked myogenic potentials after a vertigo attack due to vestibular neuritis. Acta Otolaryngol 126:364-7, 2006.
10. Nakaya M, Dohi M, Okunishi K, Nakagome K,
Tanaka R, Imamura M, Baba S, Takeuchi N, Yamamoto K, Kaga K. Noninvasive system for evaluating allergen-induced nasal hypersensitivity inmurine allergic rhinitis. Lab Invest 86:917-26,
2006.

11. Park JS, Onodera T, Nishimura S, Thompson RF,
Itohara S. Molecular evidence for two-stage learning and partial laterality in eyeblink condi-tioningof mice. Proc Natl Acad Sci U S A 103:5549-54,
2006.
12. Ogata E, Yumoto M, Itoh K, Sekimoto S, Karino S,
Kaga K. A magnetoencephalographic study of Japanese vowel processing. Neuroreport 17:1127-31,
2006.
13. Otake R, Kashio A, Sato T, Suzuki M. The effect of
optokinetic stimulation on orientation of sound lateralization. Acta Otolaryngol 126:718-23, 2006.
14. Sakai Y, Karino S, Kaga K. Bone-conducted auditory brainstem-evoked responses and skull vibratory velocity measurement in rats at frequencies of
0.5-30 kHz with a new giant magnetostrictive bone
conduction transducer. Acta Otolaryngol 126:92633, 2006.
15. Sakata A, Nakahara H, Murofushi T. A case of severe dyspnea caused by relapsing polychondritis.
Auris Nasus Larynx 33:215-8, 2006.
16. Sasaki T, Toriumi S, Asakage T, Kaga K, Yamaguchi D, Yahagi N. The toothbrush: a rare but potentially life-threatening cause of penetrating oropharyngeal trauma in children. Pediatrics 118:
e1284-6, 2006.
17. Suzuki M, Otake R, Kashio A. Effect of corticosteroids or diuretics in low-tone sensorineural hearing loss. ORL J Otorhinolaryngol Relat Spec 68:
170-6, 2006.
18. Suzuki M, Suzukawa K, Ogawa M, Suzuki T. Salivary duct carcinoma with comedonecrosis in themobile portion of the tongue. J Laryngol Otol 120:e13, 2006.
19. Takai Y, Murofushi T, Ushio M, Iwasaki S. Recovery of subjective visual horizontal after unilateral
vestibular deafferentation by intratympanic instillation of gentamicin. J Vestib Res 16:69-73, 2006.
20. Takeda H, Suzuki K, Kumakawa K, Kumakagai F,
Iba M. Cochlear implantation for patients withtemporal bone fracture. Cochlear Implant and Related Sciences:49-52, 2006.
21. Tanaka K. A case of metastases to the paranasal
sinus from rectal mucinous adenocarcinoma. Int J
Clin Oncol 11:64-5, 2006.
22. Tsunoda K, Tsunoda A, Ishimoto S, Kimura S.
Clinical applications of commercially available

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video recording and monitoring systems: inexpensive, high-quality video recording and monitoring
systems for endoscopy and microsurgery. Surg
Technol Int 15:41-3, 2006.
23. Tsunemi T, Sakai Y, Tsunoda K, Irie Y, Wada Y.
Neuro-Behcets/neuro-Sweets disease presents simultaneously with severe tonsillitis, and features
mimicking bacterial meningitis with skin lesions.
Intern Med 45:1315-7, 2006.
24. Nishiyama K, Hirose H, Masaki T, Nagai H, Hashimoto D, Usui D, Yao K, Tsunoda K, Okamoto M.
Long-term result of the new endoscopic vocal foldmedialization surgical technique for laryngeal palsy.
Laryngoscope 116:231-4, 2006.
25. Ushio M, Iwasaki S, Sugasawa K, Murofushi T.
Superficial siderosis causing retrolabyrinthine involvement in both cochlear and vestibular branchesof the eighth cranial nerve. Acta Otolaryngol
126:997-1000, 2006.
26. Ushio M, Murofushi T, Okita W, Suzuki M, Kaga
K. The effectiveness of wedge shoes in patientswith insufficient vestibular compensation. Auris
Nasus Larynx 34:155-8, 2007.
27. Ushio M, Takeuchi N, Kaga K. Evaluation of recovery from transient facial palsy following canalplasty and tympanoplasty for the treatment of congenital aural atresia. Ann Otol Rhinol Laryngol
115:749-53, 2006.
28. Watanabe K, Kondo K, Takeuchi N, Nibu K, Kaga
K. Age-related changes in cell density and the proliferation rate of olfactory ensheathing cells in thelamina propria of postnatal mouse olfactory mucosa. Brain Res 1116:82-92, 2006.
29. Yamasoba T, Goto Y, Komaki H, Mimaki M, Sudo
A, Suzuki M. Cochlear damage due to germanium-induced mitochondrial dysfunction in guinea
pigs. Neurosci Lett 395:18-22, 2006.
30. Yamasoba T, Kondo K. Supporting cell proliferation after hair cell injury in mature guinea pig
cochlea in vivo. Cell Tissue Res 325:23-31, 2006.

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Department of
Rehabilitation Medicine
Professor
Nobuhiko Haga, M.D.

Homepage

http://www.h.u-tokyo.ac.jp/patient/depts.html

Introduction and Organization
The Department of Rehabilitation Medicine was established by Ministry of Education, Culture, Sports,
Science and Technology in April 2001. It is one of thenewest fields in Graduate School of Medicine, theUniversity of Tokyo. It belongs to the Sensory andMotor System Science Course of the Surgical Science
Division. Current authorized staff is only one professor.
This department derives from the establishment of
the physical therapy room in the central diagnostic andtherapeutic sections in order to develop the clinicalpractice of rehabilitation medicine in 1963. The chair ofprofessor was set up as a full-time director of the central rehabilitation service in 1984, but the formal title
remained a physical therapy department.
Rehabilitation medicine is a newly established clinical section which was born in development of the modern principle of the medical health service by which itcame to value the enhancement of not only adding
years of patient's life but also adding life to the years.
Regardless of the rapid expansion of needs, acknowledgment of rehabilitation medicine was delayed in theframe of the old-fashioned clinical departments. In ourcountry, it was 1996 when the rehabilitation specialty
was authorized as formal clinical practice by the former
Ministry of Health and Welfare.
On the other hand, it was positioned as an assistanceinstructor in the sensory and motor system medicine
department with shifting to the graduate school course
systems since 1995 to 97 in the University of Tokyo.
Finally, the rehabilitation medicine field was installedin the sensory and motor system medicine department

by a budget step of 2001. We have accepted the graduate school student formally since fiscal year 2001.
However, the arrangement of additional teaching staff
is not still materialized. Therefore, the staff of thegraduate school is only one professor. Nine students
have entered the graduate school by 2006, and three ofthem were granted Ph.D.

Clinical activities
There is not enough doctors arranged for the department of rehabilitation medicine, and we cannot run own
beds for rehabilitation patients at present. The professor
serves as a director of Central Rehabilitation Service
Department of the University of Tokyo Hospital. Bothdepartments are united and engage in clinical practice.
We have at present no charged ward, and treat about
1,000 new referrals annually from almost all the departments of the university hospital. We always takecharge of about 150 patients corresponding about 15%of the whole number of inpatients. We also see 15 people per day at the outpatient rehabilitation setting. The
numerical ratio of outpatient is being reduced in orderto give priority to the clinical service corresponding toneeds expansion of service to inpatients.

Teaching activities
We have provided several clinical curriculums on
rehabilitation medicine for 4th, 5th, and 6th year medical students since 1973. The systematic lecture series
for 4th year medical students (M2) include the subjects
on rehabilitation for disorders such as cerebrovascular245

disturbances, spinal cord injuries and spina bifida, neuromuscular diseases, bone and joint diseases, and cerebral palsy as well as on outline of rehabilitation, welfare system, and prostheses / orthoses . We have provided a clinical practice in small group, so-called bedside learning for 5th year students from Wednesday to
Friday every other week. They experience a few patients and learn how to take a patients’ history, physicalfindings, functional evaluation, and how to plan rehabilitation programs. We have introduced a few of elective students for clinical clerkship to our collaborating
hospitals with specialized rehabilitation ward.
In addition, we have provided the training of comedical students including physical therapy and occupational therapy. Twenty students or more come andstay at the university hospital annually as a long-term
clerkship from several PT/OT training schools.
Nine graduate school students entered by 2006 andthree of them acquired a degree of Ph.D. and graduated.

Research activities
Our research activities are growing up. In 2006, theCentral Rehabilitation Service Department moved to
the new building and a research laboratory was provided for the first time. As the motion analysis system
was partially renewed, we are planning our researches
mainly in the field of musculoskeletal disabilities. In
addition, we are planning collaborating researches withother departments in our hospital, other faculties in our
university, and institutions outside the University ofTokyo. The ongoing and scheduled projects are as follows.
1) 3D-motion analysis of patients with joint disorders
in the lower extremities
2) Estimation of supported motion by humanmachine coadaptation system
3) Analysis of hemodynamic changes in the lower
extremities with passive motion4) Estimation of standing balance and the effect bypassive stimulation
5) Analysis of motion and energy expenditure in theactivities of daily living in the physically disabled
6) Non-invasive evaluation of lower limb motor
function in spina bifida
7) Prevention of requiring long-time care with physical exercise

8)

Disabilities and handicaps in patients with skeletal
dysplasias
9) Mechanism of physical therapy on the change ofpain and perceptional threshold10) Evaluation of higher brain dysfunction

References
1. Chiba Y, Yamaguchi A, Eto F. Assessment of sensory neglect: a study using moving images. Neuropsychol Rehabil. 2006;16:641-652.
2. Haga N, Masuda K, Takikawa K. Osteochondral
destruction in the hand following bee stings: a casereport of an infant. Hand Surg. 2006;11(3):143145.
3. Itoh T, Shirahata S, Nakashima E, Maeda K, Haga
N, Kitoh H, Kosaki R, Ohashi H, Nishimura G,
Ikegawa S. Comprehensive screening of multiple
epiphyseal dysplasia mutations in Japanese population. Am J Med Genet Part A. 2006;140A:12801284.
4. Kanamori Y, Tomonaga T, Sugiyama M, Hashizume K, Goishi K, Haga N. Bizarre presentation of
epigastric heteropagus: report of a case. Surg Today.
2006;36:914-918.
5. Kasuya D: Acupuncture for diabetic neuropathy.
KAIM. 2006;1(2):13-20.
6. Saotome T, Sekino M, Eto F, Ueno S. Evaluation ofdiffusional anisotropy and microscopic structure inskeletal muscles using magnetic resonance. Magnetic Resonance Imaging. 2006;24:19-25.
7. Takikawa K, Haga N, Maruyama T, Nakatomi A,
Kondoh T, Makita Y, Hata A, Kawabata H, Ikegawa S. Spine and rib abnormalities and stature in
spondylocostal dysostosis. Spine. 2006;31:E192197.

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Department of Anesthesiology
Professor
Yoshitsugu Yamada, M.D., Ph.D.

Associate Professor
Tomoki Nishiyama, M.D., Ph.D.

Lecturer
Ryo Orii, M.D., Ph.D.

Kyung-Ho Chang, M.D., Ph.D.

Takami Komatsu, M.D., Ph.D.

Instructor
Hiroshi Sekiyama, M.D.,
Yuichiro Saito, M.D.,
Masahiro Suzuki, M.D.,
Makoto Ogawa, M.D.,
Mitsuaki Muroya, M.D.,
Atsuko Satou, M.D.,
Hirotaka Ito, M.D., Ph.D.,

Homepage

Makoto Ogawa, M.D., Nobuko Ito, M.D., Ph.D.,
Nobuhide Kin, M.D.,
Takayuki Kitamura, M.D.,
Toshiya Tomioka, M.D., Ph.D.,
Erika Sano, M.D.,
Junichi Ninagawa, M.D.,
Yoshie Suzuki, M.D.,
Nagara Ono, M.D.,
Kaori Fujita, M.D.,
Woonkwan Hyun, M.D.,
Noriaki Iwasaki, M.D., Kenji Takeda, M.D., Ph D.,

http://www.h.u-tokyo.ac.jp/patient/depts/aprc_md.html/
http://www.anes.umin.ne.jp/

Introduction and Organization
The Department of Anesthesiology was establishedin 1952. Our department has residents, chief residents
besides the members above. We introduce the activities about Teaching, Research and Clinical work ofour department.

Clinical activities
Our clinical activities can be divided into two areas;
surgical anesthesia in the operating theater and a pain
clinic.
Anesthesia service including pre and post-operative
care is given every day for elective and emergency
surgery. We provide general anesthesia for various
kinds of surgeries including open heart surgery (adults
and pediatrics) and liver transplant, spinal/epidural
anesthesia and monitored anesthetic care for electro-convulsion therapy. Recently, the number of highrisk or geriatric patents is increasing. In addition,

more than 20% of the surgery (about 8000 cases intotal per year) spends more than eight hours. A new
operating theater opened in January 2007 and the demand for sufficient number of competent anesthesiologists is increasing.
Pain clinic services are provided for out-patients(including patients in the ward of the other department) on a daily basis in all areas of painful diseases.
We also provide preoperative anesthetic consult service for patients who have various medical diseases.
From April 2006 to April 2007, the number of ambulatory patients was about ten thousand; four hundredand forty of those were newcomer patients. Currently
we have three beds in the ward. Annually, we provide
inpatient service for sixty patients in our ward as well
as for seven hundred and twenty patients in otherwards. Preoperative anesthetic consults were done fornine hundred and fifty patients last year.

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Teaching activities
We give lectures for fourth year medical students
and provide clinical education for fifth and sixth year
medical students on a man-to-man basis with our faculty staff members. The lectures of the last year were
the history of anesthesia and the preliminary consideration, the mechanisms of anesthesia, inhalational
anesthesia, intravenous anesthesia and circulation, thebalance of body fluid, acid-base balance, muscle relaxants, the management of the patient during anesthesia, monitoring, resuscitation, pain clinic and thephysiology and the management of pain.
The curriculum of bedside learning consists of threemajor contents: learning a practice of anesthetic management for patients undergoing surgeries, observing
a practice of pain management for outpatients suffering from intractable pain, and interactive lectures on
specific topics. During the practice of anesthetic
management, we teach students technique of examinations and physiological- and pharmacological-knowledge which are essential for the management of patients in the peri-operative period. Throughthe practice of pain management, we teach students
causes of intractable pain as well as procedures ofnerve block. We schedule 5 lectures entitled “introduction to anesthesiology”, “airway management”,“central venous catheterization”, “spinal anesthesia”
and “pain clinic”. These 5 lectures cover fundamental
knowledge of basic procedures which medical students should acquire. Moreover, students can experience procedures of tracheal intubation, central venous
catheterization and spinal anesthesia using simulators.
Each student is required to prepare a case report ofanesthetic management and a paper on anesthetics andcardiovascular drugs in peri-operative use. We discuss
the contents of the reports and papers with students at
the end of bedside learning, for further comprehension.

Research activities
We have seven research groups and their fields include respiration, circulation, pain, immune systemand shock.
These are recent major subjects of our research.
1) A role of cytokine signaling in acute lung injury2) Evaluation of optimal ventilatory strategy for respiratory failure3) Modification of immune system by anesthetics
4) Signal transduction pathway related to apoptosis
activated by sepsis or ischemia-reperfusion insult5) investigation of pathophysiology of shock6) A role of lipid mediators in organ damage mediated by ischemia-reperfusion injury of a mouse
lower limb
7) A role of lipid mediators in the formation of hyperalgesia
8) Antihyperalgesic and antipruritic effects of alpha2-adrenergic agonists
9) A role of spinal microglial cells in the development of inflammation-mediated neuropathic pain10) spinal contribution for analgesic pathway11) Mechanism of Pruritoceptive and Neurogenic Itch
12) Dose-escalation of sublingual buprenorphine inpatients with chronic pain13) Analysis of electroencephalography during general anesthesia
14) Invention and evaluation of a new airway device15) Clinical evaluation of neurological sequelae after
cardiac surgery16) Development and assessment of the system fortreating waste anesthetic gases: against global
warming

References
1. Shu H, Arita H, Hayashida M, Chiba S, Sekiyama
H, Hanaoka K.. Inhibition of morphine tolerance
by processed Aconiti tuber is mediated by kappa-opioid receptors. J Ethnopharmacol. 2006 Jun
30;106(2):263-71.
2. Chi Li, Hiroshi Sekiyama, Masakazu Hayashida,Toshinobu Sumida, Hideko Arita, Kazuo Hanaoka,Effect of repeated topical application of clonidine cream in a rat model of postoperative pain ,PAIN RESEARCH, 21 : 25-32, 2006.
3. Mizuno J, Gauss T, Suzuki M, Hayashida M, Arita
H, Hanaoka K . Encephalopathy and rhabdomyolysis induced by iotrolan during epiduroscopy.
CAN J ANESTH.2007 54:49-53.
4. Hashimoto T, Okudo N, Orii R et al. Intraoperative blood salvage during liver resection,
RCT. Annals of Surgery (in press, 2007)

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5. Nishiyama T. Antithrombin can modulate coagulation, cytokine production, and expression ofadhesion molecules in abdominal aortic aneurysm
repair surgery. Anesth Analg 2006.102(4):1007-11
6. Nishiyama T, Matsukawa T, Yamashita K. Comparison between neurotropin and mepivacaine forstellate ganglion injection. J Anesth 2006. 20 (3):240-2
7. Nishiyama T, Yokoyama T, Yamashita K. Effects
of protease inhibitor, ulinastatin, on coagulationand fibrinolysis in abdominal surgery. J Anesth
2006. 20 (3) :179-82
8. Nishiyama T. Analgesic effects of systemic midazolam: comparison with intrathecal administration. Can J Anesth 2006.53 (10) :1004-9
9. Nishiyama T, Nakamura S, Yamashita K. Effectsof the electrode temperature of a new monitor,
TCM4TM on the measurement of transcutaneous
oxygen and carbon dioxide tension. J Anesth 2006.
20 (4 ):331-4
10. Nishiyama T, Nakamura S, Yamashita K. Comparison of the transcutaneous oxygen and carbon
dioxide tension in different electrode locations
during general anaesthesia. Eur J Anaesthesiol
2006.23 (12) :1049-54
11. Mizuno J, Yoshiya I, Yokoyama T, Yamada Y,
Arita H, Hanaoka K: Age and sex-related differences in dose-dependent hemodynamic response
to landiolol hydrochloride during general anesthesia. Eur J Clin Pharm. 2007 (in press)
12. Mizuno J, Muroya M, Gauss T, Yamada Y, Arita H,
Hanaoka K. Effect of 2.5% sevoflurane at PaCO2
30 mm Hg for epileptic focus resection on hemodynamics and hepatic and renal function. J Anesth.
2007 (in press)
13. Mizuno J, Gauss T, Suzuki M, Hayashida M, Arita
H, Hanaoka K. Encephalopathy and rhabdomyolysis induced by iotrolan during epiduroscopy.
Can J Anesth. Jan; 54(1): 2007 (in press)
14. Mizuno J, Mohri S, Shimizu J, Suzuki S, Mikane
T, Araki J, Matsubara H, Morita T, Hanaoka K,
Suga H. Starling-effect-independent lusitropism
index in canine left ventricle: Logistic time constant. Anesth Analg. 2006 Apr;102(4): 1032-9.
15. Xue F, Zhang G, Liu J, Li X, Sun H, Wang X, Li C,
Liu K, Xu Y, Liu Y. A clinical assessment of the
Glidescope videolaryngoscope in nasotracheal in-tubation with general anesthesia. J Clin Anesth.
2006 Dec;18(8):611-5.
16. Ong BY, Arneja A, Ong EW. Effects of anesthesia
on pain after lower-limb amputation. J Clin
Anesth. 2006 Dec;18(8):600-4.
17. Ito N, Hirota K, Momoeda K, Iwamori M. Change
in the concentration of neutrophil elastase in bronchoalveolar lavage fluid during anesthesia and its
inhibition by cholesterol sulfate. Transl Res. 2006
Aug;148(2):96-102.

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Department of Emergency andCritical Care Medicine
Professor
Naoki Yahagi, M.D.

Lecturer
Yukio Tanaka, M.D., Ph.D.

Associate
Shoichi Katada, M.D.,
Yoichi Kitsuta, M.D.,
Tsuneo Suzuki, M.D.,
Toshihiro Morita, M.D.,

Takeshi Ishii, M.D.,
Kyoko Komatsu, M.D.,
Susumu Nakajima, M.D., Ph.D.,
Daisuke Yamaguchi, M.D.,
Yasushi Imai, M.D.

Staff
Hiroshi Shinbori, M.D.,
Shinji Akitomi, M.D.

Homepage
Introduction and Organization
Department of Emergency and Critical Care Medicine was established in 1965, as the emergency service within the Central Clinical Service Facilities of
the University of Tokyo Hospital and at the same timeas the intensive care service for in-hospital patients, it
became a tertiary emergency care and critical carecenter in the metropolitan Tokyo and also became theprincipal teaching facility of the University of Tokyo.
It is a designated Level I Trauma Center, and also thehome of one of the newest Life Flight aeromedical
services in the country.
The Emergency Center sees approximately 16,800
patients per year. It contains major trauma and cardiac
resuscitation rooms complete with STAT X-ray andfull monitoring and resuscitation equipment. There are
9 treatment spaces including space for orthpedics,
gynecology, and optho-ENT evaluations. X-ray, rapid
spiral CT, ultrasound, angiography and STAT Lab arelocated adjacent to the Emergency Center.

In September, 2001, the University of Tokyo Hospital opened the In-patient Ward A and our department
has necessarily extended services for management of
ICU/CCU, MHCU and HCU.
The new Critical Care Center contains adult intensive care unit (ICU) of 8 beds, coronary care unit
(CCU) of 6 beds, surgical high care unit (SHCU) of 36
beds, medical high care unit (MHCU) of 15 beds, pediatric intensive care unit (PICU) of 6 beds and neonatal intensive care unit (NICU) of 6 beds.
The Emergency Care Center and the Critical Care
Center see an excellent mix of multiple trauma,
high-acuity medical, surgical, pediatric, and gynecologic patients. The Life Flight service provides another opportunity for exposure to critically ill patients.
Consult services are available from all of the clinicaldepartments of the Medical School.

Clinical activities
Our clinical activities are divided into four catego-

252

ries as follows:
1) Emergency medicine
Our department is responsible for not only tertiary emergency but also primary and secondary
emergency care on 24-hour-a-day basis. In the 2004,
we had 6,452 ambulance patients out of total 17,370
ER outpatients.
The new ER, four times the size of the present
ER was built in November, 2006. The facility has 5
consultation rooms, 4 specialized consultation
rooms for dentistry, ophthalmology, otorhinolaryngology and gynecology, 2 resuscitation bays, 1 operating room and 11 observation beds.
2) Intensive care
Staff members specialized in internal medicine,cardiovascular medicine, orthopedic surgery, surgery, neurosurgery or anesthesiology create “thesemi-closed ICU” model. We are responsible for theentire care of the critically ill patients (i.e. patientswith respiratory insufficiency such as ARDS, withsepsis, with MOF, with shock), post-operative patients, and tertiary emergency patients, placing anemphasis on evidence-based medical therapy. We
had 1,000 ICU patients in the 2004. In 2006, thenumber of beds in ICU will increase to 16 and thefacility will include the 24 beds for the surgical ICU
patients by 2007.
3) Bed management
The objective of bed management services is toprovide a timely and appropriate bed allocation for
all the patients. In our hospital, patients are allocated to three types of wards, that is, general ward,
HCU and ICU/CCU in accordance with their critical condition. The surgical HCU undertakes theleading bed management in the hospital to ensure
maximum performance as an acute hospital.
4) Risk management
It is split into two categories – in-hospital andout-hospital disasters. In regard to in-hospital risk
management, including “code blue emergency”, weare responsible for patient safety on 24-hour/
365-day basis. And in regard to out-hospital risk
management, our hospital has been authorized by

the Tokyo Metropolitan Government as a disasterbase hospital, and also the Government has requested the formation of Disaster Medical AssistantTeam (DMAT) from us. We are now proceedingwith a drastic revision of in-hospital manual fordisaster control, holding seminars on disaster medicine, and enforcing the disaster training. We areplanning to set oxygen and medical suction equipment on the passageways in the new ER within2006 fiscal year in order to treat the large number ofdisaster patients.

Teaching activities
1) Six hours of lecture for the 2nd year medical student, the topics include the prehospital emergency
care, the initial evaluation of emergency patients,
disaster medicine, serious infections disease, andmedical equipment. Four hours of simulation training of Basic Life Support.
2) One month of clinical clerkship and 1 week of
bed-side training for the 3rd year. ACLS Basiccourse (ICLS) is held for the participants in theclinical clerkship program, and successful completion of this course will enable students to be ICLS
certified.
3) Clinical integrated lecture for the 4th year students
includes diagnosis and treatment of serious patientsusing case studies of shock, conscious disorder,
trauma, intoxication, infections disease, burns, hypothermia, and convulsion. After learning a ACLS
course, students experience the real practice of
emergency medicine as fellow passengers in theambulance and as 2.5-day trainees in affiliated hospitals’ emergency centers.
In conformity with the guideline by Ministry of
Health, Labour and Welfare, all residents learn andpractice emergency medicine and primary care at
every level, primary, secondary and tertiary. The
residents are trained in the ACLS Basic (ICLS)
during resident year to obtain the knowledge andskills in CPR.
Junior residents are also assigned to ICU services
to gain the knowledge of intensive care from pathophysiological and internal medicine’s point of view.
In the senior resident program in 2006, we willtrain the new residents to be skilled in advanced

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critical care medicine including primary caretrauma, MOF, shock, and equipment support.
As medical aspects of disaster management, we
provide the residents with lectures based on
MIMMS (Major Incident Medical Management andSupport) program, triage training, and risk communication techniques using wireless network. In addition, we produce the seminar for nurses such as
medical support in the big earthquake.

Research activities
The on-going researches include “the Vital Care
Network System” which manages the great number ofhigh-risk people continually, electrolyzed water, elucidation of peripheral neural regulation of heart, andbrain resuscitation. In collaboration with Departmentof Pharmacy, Department of Clinical Laboratory
Medicine, Department of Infectious Diseases, we focus on several clinical research on issues including
intra-nuclear transcription of β-D-glucan in blood
products .

References
1. Kitsuta Y, Suzuki N, Sugiyama M, Yamamoto
Changes is consciousness level and association
with hyperglycemia as tool for predicting andpreventing re-bleeding after spontaneous subarrachnoid hemorrhage Pre-hospital and disastermedicine, 2006; 21(3), 190-195.
2. Kobayashi K, Ikeda H, Higuchi R, Nozaki M,
Yamamoto Y, Urabe M, Shimazaki S, Sugamata N,
Aikawa N, Ninomiya N, Sakurai H, Hamabe Y,
Yahagi N, Nakazawa H. Epidemiological andoutcome characteristics of major burns in Tokyo.
Burns 2005; 31S: S3-11.
3. Hale SI, Kloner RA, Katada S, Obayashi T, Ishii T,
Nakajima S, Yahagi N. Myocardical ischemia andinfarction. In Tisherman SA and Sterz F, editors.
Therapeutic Hypothermia. New York: Springer;
2005. pp191-209.

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Department of Health Sociology
Associate Professor
Yoshihiko Yamazaki, Ph.D.(Dr.Hlth.Sc.)

Homepage

http://www.hlthsoc.m.u-tokyo.ac.jp/indexj.htm/

Introduction and Organization
The Department of Health Sociology is one of thetwo departments which ex-Depautment of Health Sociology was devided into in 1997, when most departments in the University of Tokyo were reorganized
into the Graduate School of the University of Tokyo.
The department of Health Sociology is one of sixteen
departments in the Graduate School of Health Sciences and Nursing. The department consists of one
Associate Professor (Head of Health Sociology), 34
graduate students (14 master course students and 20
doctor course students) including 2 international students and 18 students qualified with nurse, and 3 research students. More than forty visiting researchers
are affiliated with the department.

Teaching activities
In Graduate Courses, School of Health Sciences andNursing, Dr. Yamazaki, A. prof. and Head of HealthSociology, runs runs two seminars every year: HealthSociology(I) in summer semester, and Health Sociology(II) in winter semester, with a lecturer, prof. Nakayama from St. Luca Nursing College.
The purpose of Health Sociology(I) is for students
to obtain a basic understanding of the health sociological approach through a quick overview of major
concepts, principles, and research in sociology ofhealth and medicine.
Health Sociology(II) introduces students to basic
methods and techniques in designing and conducting
social research- in general, both quantitative andqualitative- in the health field. For these years, thisseminar has been provided as Introduction to Multivariate Statistical Methods, and designed to learn thebasic statistical methods such as factor analysis,
analysis of variance/covariance, multiple regression
analysis, multiple logistic regression analysis, andstructural equation modeling. In the fiscal 2006 themembership in each seminar above-mentioned was 25– 30 and over.
For the graduate students and the other members in
Dept. of Health Sociology, a workshop and a journal
club are held every week. In the former, a student’s
research proposal or paper is to be reported and discussed. In the latter, a student is supposed to introduce
an English article in the recent issue of an international refereed journal.
In our department in the fiscal 2006, 5 MC students
submitted Master Thesis and gained Master’s Degree.
Three DC students submitted Doctoral Dissertationand got Doctor’s Degree. Three graduate students
have got a job as a university teacher, professor, or
researcher.
In Undergraduate Courses, School of Health Sciences and Nursing, our department is in charge of thefollowing subjects as: Health Sociology (with a lecturer, Dr. Tamura), Social Welfare and Social Security(with two lecturers, Dr. Sakano from Okayama Prefectural University and Prof. Takagi from Keio University), Social Research Method Practice, Social and
Human Relations, Graduation Thesis (many graduate
students the last three subjects are shared with many
graduate students in Dept.of Health Sociology), andthe other two.

Research activities
Our department studies social and psychologicalfactors related to health problems and health care systems, through developing and applying theories, con-

257

cepts and methods, which have been developed in sociology, psychology, and social and behavioral sciences.
We have been conducting the following 7 research
projects these two years.
1. Studies on Antonovsky’s Salutogenesis and Sense
of Coherence (SOC) Concept
We have introduced Antonovsky’s Salutogenesis
and its core concept ‘Sense of Coherence (SOC)’
to Japanese fields of health and stress. The objective of this project is to develop and apply Japanese version Antonovsky’s SOC scale to examine
SOC and correlates among different population,
people with chronic illness/disability, and so on.
2. Study on People with Medically Induced HIV
Nearly 1,500 hemophilia patients were infectedwith HIV through blood products in the mid
1980’s in Japan, and so far more than five hundred
patients have died of AIDS and others. They are
suffering not only from health damage but also
various types of stigma and discrimination. In thisproject, several research studies are being conduced in order to explore the problems of theirlives, and to suggest the needed social supports
3. Studies on Social Differences and Inequalities in
HealthThis project is designed to explore evidence aboutsocio-economic differences in health, especiallyamong the middle-aged, in Japan. Another purpose of this project is to cinsider possible explanations for these differences and the implications
for policy.
4. Studies on Changing Professional-Patient Relationship and Patient Autonomy
The aim of this project is to examine the current
situation of professional-patient relationship andpatient autonomy in Japan, and to derive newtheories. Both empirical and theoretical studies
have been conducted from various perspectives.
5. Studies on “Way of Working and Living” and Fatigue/Stress of Working People
Recently Japanese industrial society has been subjected to the never-experienced structural changes.
The aims of this project are to explore the effectsof these changes on “ways of working and living”,
work-family balance and fatigue/stress of working

people, and to clarify the mechanism of the effects.
6. Studies on Characteristics of the Physical andPsychological Distresses in Human Service Work
Human service work is spread over the many
fields including medicine, nursing and caring. The
aims of this project is to examine the characteristics of the psychological and physical distress ofhuman service workers and their related factors.
7. Studies on the Onset of Pneumoconiosis among
Tunnel Construction Workers
In Japan, many tunnel construction workers suffered from the onset of severe pneumoconiosis in
1970’s. It is still continuing in 1990’s. The purpose of this research project is to reveal the process and the related factors on the onset of pneumoconiosis in recent years.

References
1. Yamazaki Y, Asakura T. Health Sciences for Waysof Living. 4th Edition, Yushindo Publisher. 2007.
(in Japanese)
2. Hirano Y, Yamazaki Y, Sakita M, Kawai K, Sato
M. The Herth Hope Index (HHI) and related factors in the Japanese general urban population.
Japanese Journal of Health Human Ecology. 2007;
73(1): 31-42.
3. Mizota Y, Ozawa M, Yamazaki M. Daily difficulty
and Desire of the bereaved: A study of bereaved
families of HIV-infected Hemophiliacs in Japan.
Bulletin of Social Medicine. 2006; 24:43-56.(inJapanese)
4. Inoue Y, Yamazaki Y, Kihara M, Wakabayashi C,
Seki Y, Ichikawa S. The intent and practice ofcondom use among HIV-Positive men who havesex with men in Japan. Aids Patient Care and STD.
2006;20(11):792-802.
5. Kawai K, Yamazaki Y. The effects of pre-entry
career maturity and support networks in workplace on newcomers’ mental health, Journal of
Occupational Health. 2006; 48:451-461.
6. Kawai K, Yamazaki Y. Newcomers’ support network structure and mental health. Japanese Journal of Health Education and Promotion. 2006;
14(2):71-81. (in Japanese)
7. Togari T, Yamazaki Y, Koide S, Miyata A. Ex-

258

amination of association between Perceived
Health Competence Scale Japanese version andsocio-economic status. Japanese Journal of Health
Education and Promotion. 2006; 14(2):82-96. (inJapanese)
8. Mizota Y, Yamazaki Y, Inoue Y. Ozawa M. Psychosocial problems of bereaved families ofHIV-infected hemophiliacs in Japan. Social Science & Medicine. 2006; 62(10): 2397-2410.
9. Seki Y, Yamazaki Y. Effects of working conditions
on intravenous medication errors in a Japanesehospital. Journal of Nursing Management. 2006;
14(2):128-139.
10. Hirano YM, Yamazaki Y, Shimizu J, Togari T,
Bryce TJ. Ventilator dependence and expressionsof need: A study of patients with amyotrophic lateral sclerosis in Japan. Social Science & Medicine.
2006; 62:1403-1413.
11. Ishikawa H, Roter DL, Yamazaki Y, Hashimoto H,
Yano E, Patient’ perceptions of visit companions’helpfullness during Japanese geriatric medical visit. Patient Education Counseling. 2006;
61:80-86.
12. Togari T, Yamazaki Y, Koide S, Miyata A. “Reliability and validity of the modified perceived
health competence scale (PHCS) Japanese version.
Japanese Journal of Public Health. 2006; 53:5157.

259

Department of Mental HealthProfessor
Norito Kawakami, M.D., Ph.D.

Assosicate Professor
Akihito Shimazu, Ph.D. (since Oct. 2006)

Assistant Professor
Toshio Mori, Ph.D.

Homepage

http://plaza.umin.ac.jp/heart/

Introduction and Organization

Teaching activities

The department was firstly established as Department of Fourth Clinical Medical Nursing in School of
Health Care and Nursing in 1957. When the School of
Health Care and Nursing was reorganized as the
School of Health Sciences in 1965, the department
was renamed Department of Mental Health. In 1992,
as School of Health Sciences became The School of
Health Science and Nursing, Department of Mental
Health became Department of Mental Health andPsychiatric Nursing. As the result of the shift to thechair system of the Graduate School of Medicine in
1996, two departments were established, Departmentof Mental Health and Department of PsychiatricNursing. Faculty, staff, and students of two departments have been working cooperatively ever since.
The department currently has faculty members introduced above, part-time lecturers, a technical specialist, visiting research fellows, 10 doctoral course
students, 7 master course students, research associates,and secretaries.
The department has two major objectives: one is toteach mental health to undergraduate and graduate
students in order to produce leading practitioners andclinical researchers in the field. The other is to conduct clinical research in the fields of mental health.
All of the activities of the department are conductedin collaboration with staff members in the departmentof psychiatric nursing.

The department is responsible for giving lectures onmental health; mental disorders; clinical psychology;
and psychometry and behavior evaluation to undergraduate students. Other than lectures, the department
provides students opportunities to practice mental
health activities in several relevant mental health facilities.
The department provides special courses on mental
health I and II, featuring occupational mental healthand research methodology of epidemiology in mental
health, respectively, in the fiscal year of 2006. The
department also provided a 1.5 hour seminar every
Wednesday evening for 20 weeks in each semester (40weeks per year) for graduate students and research
students, inducing presentation of literature review
and lectures by guest speakers. The seminar included
presentation of a research plan by each graduate student and relevant discussion, as well.

Research activities
The departments conduct research on mental healthand psychosocial stress and provide education/trainingof professionals in related fields from global perspectives. The World Mental Health Japan survey, which ispart of a WHO international collaboration, is a largest
epidemiologic study of mental disorders amongcommunity residents in Japan. Assessment of health

260

effects of job stressors and evaluation of effectivenessof interventions to reduce job stress are also one ofcore research activities of the department. Research in
the department also includes various other topics, suchas psychiatric rehabilitation, clinical psychology,
psychotherapy, child and adolescent psychiatry; anddevelopmental disorders. Most of the research has
been conducted in a close collaboration with researchers in other domestic and foreign institutions/universities.

References (Jan.-Dec., 2006)
1.

2.

3.

4.

5.

6.

Shimazu A, Umanodan R, Schaufeli W B.: Effects of a brief worksite stress management program on coping skills, psychological distress andphysical complaints: a controlled trial. Int Arch
Occuo Environ Health. 2006; 80: 60-69.
Wada K, Satoh T, Tsunoda M, Aizawa Y, and The
Japan Work Stress and Health Cohort Study
Group: Associations of health behaviors on depressive symptoms among employed men in Japan. Industrial Health. 2006; 44: 486-492.
Takao S, Tsutsumi A, Nishiuchi K, Mineyama S,
Kawakami N. Effects of the job stress education
for supervisors on psychological distress and job
performance among their immediate subordinates: A supervisor-based randomized controlled
trial. Journal of Occupational Health. 2006; 48:494-503.
Honjo K, Kawakami N, Takeshima T, Tachimori
H, Ono Y, Uda H, Hata Y, Nakane Y, Nakane H,
Iwata N, Furukawa TA, Watanabe M, Nakamura
Y, Kikkawa T. Social class inequalities in selfrated health and their gender and age group differences in Japan. J Epidemiol. 2006; 16(6):22332.
Ishizaki M, Kawakami N, Honda R, Nakagawa H,
Morikawa Y, Yamada Y; Japan WorkStress and
Health Cohort Study Group. Psychosocial work
characteristics and sickness absence in Japaneseemployees. Int Arch Occup Environ Health.
2006; 79(8): 640-6.
Koyama T, Tachimori H, Osada H, Kurita H.
Cognitive and symptom profiles in highfunctioning pervasive developmental disorder nototherwise specified and attention- deficit/ hyper-

activity disorder. J Autism Dev Disord. 2006;
36(3): 373-80.
7. Naganuma Y, Tachimori H, Kawakami N, Takeshima T, Ono Y, Uda H, Hata Y, Nakane Y, Nakane H, Iwata N, Furukawa TA, Kikkawa T.
Twelve-month Use of Mental Health Services inFour Areas in Japan: Finding from the World
Mental Health Japan Survey 2002-2003. Psychiatry and Clinical Neurosciences. 2006; 60(2):240-8.
8. Honjo K, Tsutsumi A, Kawakami N. What accounts for the relationship between social classand smoking cessation? Results of a path analysis.
Social Science and Medicine. 2006; 62: 317-28.
9. Kawakami N, Takao S, Kobayashi Y, Tsutsumi A.
Effects of web-based supervisor training on job
stressors and psychological distress among
workers: A workplace-based randomized controlled trial. Journal of Occupational Health.
2006; 48: 28-34.
10. Kawakami N, Tsutsumi A, Haratani T, Kobayashi
F, Ishizaki M, Hayashi T, Fujita O, Aizawa Y,
Miyazaki S, Hiro H, Masumoto T, Hashimoto S,
Araki S. Job Strain, Worksite Support, and Nutrient Intake among Employed Japanese Men and
Women. Journal of Epidemiology. 2006; 16:
79-89.
11. Kondo K, Kobayashi Y, Hirokawa K, Tsutsumi A,
Kobayashi F, Haratani T, Araki S, Kawakami N.
Job strain and sick leave among Japanese employees: A longitudinal study. International Archives of Occupational and Environmental
Health. 2006; 79: 213-9.

261

Department of Biostatistics
Professor
Yasuo Ohashi, Ph.D.

Associate Professor
Yutaka Matsuyama, Ph.D.

Lecturer
AssociateTakuhiro Yamaguchi, Ph.D.
Yoichi Ito

Homepage

http://www.epistat.m.u-tokyo.ac.jp/

Introduction and Organization
The Department of Epidemiology and Biostatistics
changed the name from “Epidemiology” in 1992 andhas responsibility for providing educational courses
on epidemiology and biostatistics to undergraduate
students as well as graduate ones. As compared to thesituation in the United States, the education of biostatistics and methodological aspects of epidemiology ispoor in Japanese universities and graduate schools,
although the necessity for collaboration with biostatisticians in clinical research (especially clinical trials) isrecently being to be claimed by clinical researchersand pharmaceutical industry. One mission of our educational courses is to provide detailed knowledge andexperiences in biostatistics/ epidemiology to students
who are expected to take part in clinical/
epidemiological research as experts and the other mission is to provide basic principles of biostatistics/
epidemiology to students who will work in many
health-related fields including nursing. Our main research project is the development of methodology forclinical/epidemiological research and it requires
keeping touch with real clinical/epidemiologicalproblems. For these purposes and research coordination, a non-profit organization titled ‘The Japan

Clinical Research Support Unit’ was established by
the faculty members in 2001, and the organization isproviding research support in design, data management and statistical analysis in many projects inside/outside the university.
The faculty of the department provided lectures in aseries of educational courses organized by ‘The
Clinical Bioinformatics Research Unit’ in 2002-2007.

Teaching activities
1. Undergraduate courses
1) Epidemiology and Biostatistics (2 credits)
2) Applied Mathematics (2 credits)
3) Statistical Methods and Information Processing(2 credits, practice)4) Design and Analysis of Epidemiological Research (2+1 credits, 1 practice)5) Medical Data analysis (2 credits)
6) Biostatistics (2 credits; for the School of Medicine)
2. Garduate courses
1) Biostatistics (4 credits)
2) Epidemiology and Preventive Health Sciences(4 credits)
3) Introduction to Medical Statistics (2 credits; for262

the School of Medicine)
3. ‘The Clinical Bioinformatics Research Unit’courses
1) Introduction of Biostatistics required for biomedical research2) Methodology of Clinical Trials (2 credits)

Research activities
1) Biostatistics and Theoretical Epidemiology
Analysis of longitudinal missing /incomplete data
Analysis of multiple events data
Analysis of QOL data
Causal analysis
Analysis of micro/macro array data
Meta analysis of epidemiological studies
2) Methodology and Information Systems for Clinical Trials
Design of clinical trials
Data management of large-scale clinical trials3) Pharmacoepidemiology4) Coordination of collaborative epidemiological/
clinical research
Japan Longitudinal Arteriosclerosis StudyJapan Diabetes Collaborative Study
5) Consultation Works

5.

6.

7.

8.

9.

References
10.
1.

2.

3.

4.

Nakamura H, Arakawa K, Itakura H, Ohashi Y etal. Primary prevention of cardiovascular disease
with pravastatin in Japan (MEGA Study): a prospective randomized controlled trial. Lancet
2006;368:1155-63.
Kuchiba A. Tanaka YN, Ohashi Y. Optimum twostage design in case-control association studies
using false discovery rate. J Hum Genet. 2006;
51:1046-54.
Sakamoto K, Matsuyama Y, Ohashi Y. Sensitivity
analysis of publication bias in meta-analysis: A
Bayesian approach. Jpn J Biomet. 2006;27:10919.
Akisaki T, Sakurai T, Takata T, Ohashi Y et al.
Cognitive dysfunction associates with white matter hyperintensities and subcortical atrophy onmagnetic resonance imaging of the elderly diabetes mellitus Japanese elderly diabetes interven-

11.

12.

13.

tion trial (J-EDIT). Diabetes Metab Res Rev
2006;22: 376-84.
Akaza H, Homma Y, Usami M, Ohashi Y et al.
Efficacy of primary hormone therapy for localized or locally advanced prostate cancer: resultsof a 10-years follow-up. BJU Int. 2006;98:573-9.
Watanabe M, Kodaira S, Takahashi T, Ohashi Y
et al. Randomized trial of the efficacy of adjuvant
chemotherapy for colon cancer with combination
therapy incorporating the oral pyrimidine 1hexylcarbamoyl-5-fluorouracil.
Langenbecks
Arch Surg. 2006; 391:330-7.
Mori T, Hirota T, Kodaira S, Ohashi Y et al. Significance of histologic type of primary lesion andmetastatic lymph nodes as a prognostic factor instage Ⅲcolon cancer. Dis Colon Rectum 2006;
49: 982-92.
Muto Y, Sato S, Watanabe A, Ohashi Y et al.
Overweight and obesity increase the risk for livercancer in patients with liver cirrhosis and longterm oral supplementation with branched- chainamino acid granules inhibits liver carcinogenesis
in heavier patients with liver cirrhosis. Hepatol
Res. 2006;35:204-14.
Doi K, Matsuyama Y, Ohashi Y. Analysis of quality of life data with death and drop-out in advanced non-small-cell lung cancer patients. Jpn J
Biomet. 2006;27:17-33.
Nakamura S, Nouso K, Sakaguchi K, Ohashi Y et
al. Sensitivity and specificity of des-gammacarboxy prothrombin for diagnosis of patientswith hepatocellular carcinomas varies according
to tumor size. Am J Gastroenterol. 2006; 101:
2038-43.
Kishimoto H, Fukunaga M, Kushida K, Ohashi Y
et al. Efficacy and tolerability of once-weekly
administration of 17.5mg risedronate in Japanesepatients with involutional osteoporosis: a comparison with 2.5-mg once-daily dosage regimen.
J Bone Miner Metab. 2006;24:405-13.
Sakamoto J, Morita S, Oba K, Ohashi Y et al.
Efficacy of adjuvant Immunochemotherapy with
polysaccharide K for patients with curatively resected colorectal cancer: a meta-analysis of centrally randomized controlled clinical trials. Cancer Immunol Immunother. 2006;55:404-11.
Shinohara Y, Minematsu K, Amano T, Ohashi Y.

263

14.

15.

16.

17.

18.

19.

20.

21.

22.

Modified rankin scale with expanded guidance
scheme and interview questionnaire: interrater
agreement and reproducibility of assessment.
Cerebrovasc Dis. 2006;21:271-8.
Ogura M, Morishima Y, Kagami Y, Ohashi Y et al.
Randomized phase Ⅱ study of concurrent andsequential rituximab and CHOP chemotherapy inuntreated indolent B-cell lymphoma. Cancer Sci.
2006;97:305-12.
Ouchi Y, Ohashi Y, Ito H, Saito Y, et al. Influences of age, sex, and LDL-C change on cardiovascular risk reduction with pravastatin treatment
in elderly Japanese patients: A post hoc analysisof data from the pravastatin anti-atherosclerosis
trial in the elderly (PATE). Curr Ther Res Clin
Exp. 2006; 67: 241-56.
Matsuba H, Kiuchi T, Tsutani K, Uchida E. Ohashi Y: The Japanese perspective on registries anda review of clinical trial process in Japan. Clinical Trial Registries: A Practical Guide for Sponsors and Researchers of Medicinal Products (edited by MaryAnn Foote). 2006:83-106.
Sone H, Tanaka S, Ishibashi S, Ohashi Y et al.
The new worldwide definition of metabolic syndrome is not a better diagnostic predictor of cardiovascular disease in Japanese diabetic patients
than the existing definitions. Diabetes Care 2006;
29:145-7.
Matsuyama Y and Morita S. Estimation of theaverage causal effect among subgroups definedby post-treatment variables. Clin Trials. 2006; 3:
1-9.
Takayasu K, Arii S, Ikai I, Matsuyama Y et al.
Prospective cohort study of transarterial
chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology 2006; 131: 461-9.
Ikai I, Takayasu K, Omata M, Matsuyama Y et al.
A modified Japan Integrated Stage score forprognostic assessment in patients with hepatocellular carcinoma. J Gastroenterol. 2006; 41:884-92.
Hasegawa K, Takayama T, Ijichi M, Matsuyama
Y et al. Uracil-tegafur as an adjuvant for hepatocellular carcinoma: A randomized trial. Hepatology 2006; 44: 891-5.
Takeuchi K, Tanaka-Taya K, Kazuyama Y, Ito

23.

24.

25.

26.

YM et al. Prevalence of Epstein-Barr virus in Japan: Trends and future prediction. Pathol Int.
2006; 56:112-6.
Kohno T, Kunitoh H, Toyama K, Kuchiba A et al.
Association of the OGG1-Ser326Cys polymorphism with lung adenocarcinoma risk. Cancer Sci.
2006;97:724-8.
Kohno T, Sakiyama T, Kunitoh H, Kuchiba A et
al. Association of polymorphisms in the MTH1
gene with small cell lung carcinoma risk. Carcinogenesis. 2006;27:2448-54.
Yaju Y, Nakayama T. Effectiveness and safety of
ritodrine hydrochloride for the treatment of preterm labour: a systematic review. Pharmacoepidemiol Drug Saf. 2006; 15: 813-22.
Sawabe M, Saito M, Naka M, Kasahara I et al.
Standard organ weights among elderly Japanese
who died in hospital, including 50 centenarians.
Pathol int. 2006;56:315-23.

264

Department ofSocial Gerontology
Professor
Ichiro Kai, M.D., M.P.H.

Associate
Miyako Takahashi, M.D., Dr.Hlth.Sc.

Homepage

Tami Saito, M.Hlth.Sc.

http://www.sg.m.u-tokyo.ac.jp

Introduction and Organization

Teaching activities

It is often voiced from the general public that recent
advancement of medicinal technology would not necessarily lead to the happiness of people: Life prolongation technology enables even the terminally ill tolive for a considerable period. How to use the technology is a serious problem in clinical practice. Also,
there is evidence that the prolongation of life expectancy for the elderly does not mean the prolongationof health and productivity, but that of morbidity. Taking another example, we are experiencing ethical dilemmas with the application of medical technology
such as genetic screenings and organ transplantation.
When we turn to the worldwide situation regarding
health, we will find poverty and unequal distribution
in terms of health resources and outcomes.
The department is studying these health-related
problems from social perspective, many of which areoften difficult to decide upon. Major topics include
elderly health, terminal care, medical ethics and international health among others. We are currently
conducting several research projects as described below.
Our educational activities include lectures, practicaltraining and supervision of writing theses for students
in graduate level as well as undergraduate level. The
department consists of one professor, five visiting lecturers, two associates, 14 graduate students (including
three international students from Nepal, Korea andPhilippines), and one research student from Brazil.

1. Graduate Courses, School of Health Sciences andNursing
1) Social Gerontology: The course is to provide
the students with the basic understanding of social sciences in the field of gerontology. The
topics include (1) the concept and measurements of quality of life, (2) the influences ofpsychosocial factors on health status, healthbehavior and health belief, and (3) policy considerations for medical care and prevention.
2. Undergraduate Courses, School of Health Sciences and Nursing
1) Health Education: This course provides fundamental understanding in health education andhealth promotion in various settings such ascommunity, workplace, school and clinics.
Emphasis is put upon preparing students to
conduct heath education in their future career asa health professional.
2) Practice in Social Surveys: This is for practicing
to conduct social surveys using questionnaire/interview method. The students are divided into several groups, and each group is
given a survey area. They will go through all
the processes of a health sociological survey,
from planning the survey to writing a reportbased on the survey. They have the opportunity
to report and discuss their surveys with eachother.

2653) Health Behavior: This seminar aims to help thestudents to practice the basic research methods
related to health behaviors. Final product will
be a research proposal and the review of relevant literature.
4) Decision-making in Health: This course introduces students to recent developments in medical and health decision-making. Topics include
the definition and measurement of quality oflife (QOL), cost-effectiveness and cost-benefit
analysis, technology assessment and optimal
allocation of scarce medical resources. Readings are selected from extensive range of literature in behavioral sciences, economics andphilosophy as well as medical decision-making.

Research activities
1) Reciprocity of Social Support on Subjective
Well-being of the Elderly: Traditional support
study emphasizes the importance of receiving
support. We examine the pattern of support exchange (i.e., receiving and providing) and its effects on the subjective well-being of the elderly inrural Japan as well as a number of Asian countries
such as Korea, Nepal, Malaysia, and Indonesia.
Intervention studies regarding intergeneration exchanges and targeting the relocated elderly are
now in progress.
2) Disability-free Life Expectancy in Japan: We calculate disability-free expectancy using alarge-scale cohort of the residents in Nagano Prefecture and examine variables influencing the life
expectancy.
3) Multi-disciplinary Collaboration in the Psychosocial Care for the People with Cancer in ClinicalSetting: The survey we performed indicated thatJapanese surgeons considered themselves mainly
responsible for medical aspects of patient care andpaid less attention to psychosocial issues. We
examine the possibilities of integrating othersupport resources such as clinical psychologists,
psychiatrists and medical social workers in theclinical practices of cancer in Japan.
4) Activities of Cancer Self-help Groups in Japan:
Although cancer self-help groups are growing
presence in Japan, they do not attract as many pa-

tients as they do in other countries such as US.
Through semi-structured interviews and a questionnaire survey, we revealed how Japanese cancer survivors and surgeons view peer support activities implemented by cancer survivors.
5) Socio-cultural Analysis of Sexuality after Cancer:
Researchers have long neglected sexuality aftercancer. Through intensive semi-structured interviews with Japanese women with breast cancer,
we examine how the cancer diagnosis and thefollowing treatments have affected their sexuality
and the whole relationship with their partners.
Based on the findings of the qualitative approach,
we intend to perform a large-scale survey on sexual complications among Japanese cancer survivors.
6) Role and Function of Ethics Committees in Japan:
In this project, we surveyed and analyzed the roleand function of ethics committees at various levels, from hospital level to national level.

References(1) Ishizaki T, Kai I, Imanaka Y: Self-rated health andsocial role as predictors for 6-year total mortality
among a non-disabled older Japanese population.
Arch. Gerontol. Geriatr. 42(1):91-99, 2006.
(2) Sakisaka K, Wakai S, Kuroiwa C, et al.: Nutritional status and associated factors in children
aged 0-23 months in Granada, Nicaragua. Public
Health 120:400-411, 2006.
(3) Sato H, Akabayashi A, Kai I: Appraisal of thepolicymaking process in Japan for gene therapy―Results of national surveys of academic societies, hospitals, and medical schools. Med. Sci.
Monit. 12(9):PH7-15, 2006.
(4) Miyata H, Shiraishi H, Kai I: Survey of the general publics attitudes toward advance planning inJapan ―How to respect patients preferences.
BMC Medical Ethics 7:11 (9 pages), 2006.
(5) Zheng YF, Saito T, Takahashi M, et al.: Factors
associated with intentions to adhere to colorectal
cancer screening follow-up exams. BMC Public
Health 6:272 (12 pages), 2006
(6) Takahashi M, Kai I, Hisata M, et al.: The association between breast surgeons' attitudes towardbreast reconstruction and their reconstruc-266

tion-related information-giving behaviors: a nationwide survey in Japan. Plast. Reconstr. Surg.
118(7):1507-1514, 2006.
(7) Sato H, Akabayashi A, Kai I: Public, experts, andacceptance of advanced medical technologies―The case of organ transplant and gene therapy
in Japan. Health Care Anal. 14(4):203-214, 2006.
(8) Takahashi M, Kai I, Hisata M, et al.: Attitudes andpractices of breast cancer consultations regarding
sexual issues ―A nationwide survey of Japanesesurgeons. J. Clin. Oncol. 24(36):5763-5768, 2006.
(9) Aita K, Kai I: Withdrawal of care in Japan. Lancet
368:12-14, 2006.
(10) Chalise HN, Brightman JD: Aging trends―Population aging in Nepal. Geriatr. Gerontol.
International 6(3):199-204, 2006.
(11) Maly RC, Umezawa Y, Ratliff CT, et al. Racial/ethnic group differences in treatment decision-making and treatment received among older
breast carcinoma patients. Cancer 106(4):957-965,
2006.
(12) Ono M, Shinozuka M, Matsumura S, et al. Japanese people’s view of an ideal primary-care physician ―A qualitative study. Asia Pacific FamilyMed. 4(3-4) (8 pages), 2006.
(13) Skirton H, Arimori N, Aoki M: A historical comparison of the development of specialist genetic
nursing in the United Kingdom and Japan. Nurs.
Health Sci. 8(4):231-236, 2006.

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Department of Biomedical
Ethics & Department of
Health Promotion Sciences
Professor
Akira Akabayashi, M.D., Ph.D.

Lecturer
Jung Su Lee, Ph.D.

Associate
Satoshi Kodama, Ph.D.

Homepage

Kenji Matsui, M.D., Ph.D.

http:// www.ethps.m.u-tokyo.ac.jp/

Introduction and Organization
The former Department of Health Administration
was established in 1967 and Dr. Tsuneo Tanaka became its first professor in 1974. He devoted himself tothe development of the community health care system
in Japan and published numerous papers concerning
the social theory of health administration and data
management systems for community health care. He
also contributed to the establishment of the School of
Health Sciences. In 1985, Dr. Atsuaki Gunji became
the second professor of the department. During Dr.
Gunji’s tenure, two major research projects were undertaken. One was “The effects of physical activity
and inactivity on health.” From 1990, a 20-day bed
rest human experimental study was conducted every
year in the context of an international cooperative research project that was supported by government
grants. The other project concerned health care systems, especially health care economics and the qualityof hospital care.
In 1996, the Department of Health Administration
developed into two departments: the Department of
Health Economics and the Department of Health
Promotion Sciences. Both were established as departments of the Graduate School of Medicine. In

1998, Dr. Yasuki Kobayashi became the professor of
the Department of Health Economics. He conducted
research into health care delivery systems in Japan. In
2001, he moved to the Department of Public Health.
From 1996 to 2002, Dr. Kiyoshi Kawakubo tookcharge of the Department of Health Promotion Sciences as the associate professor.
In June 2002, Dr. Akira Akabayashi became professor of the Department of Health Economics. Professor Akabayashi’s area of research is biomedical
ethics. In April 2003, the Department of Health Economics was restructured and named the Department of
Biomedical Ethics.
Staff members of the two departments include a
professor, a lecturer, two associates, and a technicalspecialist. All five members, a total of eight lecturers
from other organizations and nine visiting researchers
contribute to department teaching and research activities.
Department graduate students included four masterprogram students and five doctoral program students(including one international student from the USA).
In this annual report, the organization and teachingactivities are reviewed followed by an explanation ofresearch activities.

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Teaching activities
Our departments highly prioritize the teaching andguidance of graduate students and their research activities. Two bachelor theses, three master thesis, andfour doctoral dissertations were completed between
April 2004 and March 2006. Our departments’ staff
members are also responsible for the following undergraduate and graduate courses.
Undergraduate Courses
Required courses
1) Health Administration (2 credits, lecture)2) Biomedical Ethics (2 credits, lecture)3) Occupational Health and Law (1 credit, lecture)
Elective courses
4) Health Care & WelfareⅠ&Ⅱ (2 credits, lecture)5) Field Work for Health Administration (2 credits,
practicum)6) Health Promotion Sciences (1 credit, lecture)7) Health Policy & Administration (2 credits, lecture)8) Introduction to Health Economics (2 credits,
lecture)Graduate Courses
1) Biomedical Ethics Ⅰ
2) Biomedical Ethics Ⅱ
3) Health Promotion Sciences Ⅰ
4) Health Promotion Sciences Ⅱ
Graduate level courses in Biomedical Ethics focus
on the analytical study of ethical theories and on thereview of several empirical studies within the field
and its related areas. The main foci in the graduate
courses of Health Promotion Sciences are the assessment and design of the health promotion projects inthe community and at the work place, the development of preventive health strategies and health promotion related to life-style related disease.

Research activities
Department of Biomedical Ethics
The Department of Biomedical Ethics is interested
in the current topics of health care ethics. We are cur-rently conducting studies in the fields of biomedical
ethics, research ethics and clinical ethics. Methodology is two-folded – theoretical and empirical. While
conducting theoretical research on ethics and philosophy of health care, we also have adopted a descriptive approach.
We have recently established the Center for Biomedical Ethics and Law (CBEL) adjunct to the Department of Biomedical Ethics (http://square.umin.ac.
jp/CBEL). The Center is funded by a ministry grant
and is aimed to provide educational opportunities bothto students and healthcare professionals outside theuniversity. The Center holds 10 faculty positions andhas started several public activities as of October 2003.
In August 2006, an international collaboration resulted
in a joint symposium with Case Western Reserve
University (Ethics Consultation in Japan and theUnited States: Past, Present and Future).
Specific research topics include;
1) Study of methods for promoting social consensus
on topics related to advanced medical technology
2) Study of the function and responsibilities of ethics
committees in Japan
3) Acceptability of advance directives in Japanesesociety4) Development of evaluative methods for biomedical ethics education
5) Ethical and psychosocial aspects of living relatedorgan transplantation
6) Publication of a medical ethics case book for Japan
7) Comparative study of clinical ethics in the Asian
region8) Historical analyses for the term “bioethics” in theJapanese context
Department of Health Promotion Sciences
The main research activity of the Department of
Health Promotion Sciences is making health policy
proposals concerning health promotion in the community and work place through experimental and survey
research. The main research fields are health behavior
and life-style related disease. The main focus of healthbehaviors are physical activity including exercise, dietand nutrition, and obesity. Our department is providing lectures and practical training with the aim of

269

helping students to understand the method of planning,
implementation and evaluation of the health promotion programs in the community and work place.
Specific research topics include;1) Development of effective health promotion programs2) Assessment of and supporting methods for healthbehavior, and the impact on health status
3) Short and long term effects of behavior change
4) Influence of behavior change on medical costs,
and cost effectiveness analysis
5) Determinants in the social and physical environment on the adherence to behavior change
6) Survey of health promotion resources in thecommunity and at the work place
7) The development of a physical activity questionnaire for the Japanese8) Multiple risk factors and health behavior
9) Glycemic index as a tool for nutritional education
10) Dietary patterns among overweight men andwomen

Publications
1. Akabayashi, A., Slingsby, B.T. Informed consent
revisited: Japan and the U.S. American Journal of
Bioethics 2006: 6(1):9-14.
2. Fujita, M., Akabayashi, A., Slingsby, B.T., Kosugi,
S., Fujimoto, Y., Tanaka, K. A model of donors’decision-making in adult-to-adult living donorliver transplantation in Japan: ‘Having no choice.’
Liver Transplantation 2006; 12(5):768-74.
3. Slingsby, B.T., Yamada, S., Akabayashi, A. Fourphysician communication styles in routine Japanese outpatient medical encounters. J Gen Intern
Med. 2006; 21(10):1057-62.
4. Sato, H., Akabayashi, A., Kai, I. Appraisal of thepolicymaking process in Japan for gene therapy:
Results of national surveys of academic societies,
hospitals, and medical schools. Med Sci Monit.
2006; 12(9):PH7-15.
5. Slingsby, B.T., Kodama, S., and Akabayashi, A.
Scientific Misconduct in Japan: The Present Paucity of Oversight Policy. Cambridge Quarterly of
Healthcare Ethics 2006; 15(3):294-297.
6. Lee JS, Kawakubo K, Park CM and Akabayashi A.

Rapidly increasing prevalence of obesity and theirconfident determinants in Korea. Korean J Health
Educ Promot 2006; 23:1-11.
7. Slingsby, BT. Professional approaches to stroke
treatment in Japan: A qualitative study. Journal of
Evaluation in Clinical Practice 2006; 12(2):218-26.

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Department of Nursing
Administration / Advanced
Clinical Nursing
Professor
Katsuya Kanda, R.N., P.H.N., Ph.D.

Associate
Minako Sasaki, R.N., P.H.N., M.S.N.
Hideyuki Kobayashi, R.N., P.H.N., B.S.N.

Homepage

http://nurs-adm.m.u-tokyo.ac.jp/2004activities.htm

Introduction and Organization
Nursing Administration department provides broad
opportunities to learn about societal issues related tonursing education, nursing ethics, nursing administration, and safety and quality issues in nursing.
Advanced Clinical Nursing department provides 1)
critical analysis and synthesis of conceptual frameworks, nursing theories and models for advanced
practice, and 2) generation and utilization of evidence
related to practice, understanding of clients, and fundamental skills.
As we expect much of the graduates to develop
their professional carriers in various settings, we areconstantly exploring new issues to make students beable to take wide and long viewpoints.

Teaching activities
A. Graduate courses
1. Nursing Administration 1 (2 credits, Lecturers)
Prof. Kanda and Affiliates
Exploration of political and administrative functional role in nursing. The course offers criticalanalysis of theories in nursing administration related to quality assurance/ improvement and costeffective/efficient care delivery systems. Discus-

sions include concepts and structures in organization, decision/policy making process, and application of management theory and nursing process tonursing administration. Theory and practice innursing education is also explored.
2. Nursing Administration 2 (2 credits, Lecturers)
Prof. Kanda and Affiliates
Studies on application of management theory tonursing administration. Focuses are on 1) issues innursing management such as budgetary management, nursing informatics, patient classification
systems, staffing, and quality improvement, and
2) issues in staff management such as staff development and continuing education. Students willlearn concepts and skills essential to solving economic issues in health care and nursing to meet
professional demands in the complexity of healthcare systems.
3. Advanced Clinical Nursing 1 (2 credits , Lecturers)
Prof. Kanda and Affiliates
An overview on models and theories in nursing,conceptual frameworks in nursing research, andclients' potential and actual physiological andpsychosocial responses to health problems. Focuses are on 1) conceptual frameworks of clients'
potential and actual physiological and psychoso-

273

cial responses to health problems, 2) health assessment skills in nursing practice, 3) measurement of clients' health and nursing intervention
outcome. Students will establish their own theoretical knowledge and practical skills essential toadvanced clinical nursing.
4. Advanced Clinical Nursing 2 (2 credits, Lecturers
and practice)Prof. Kanda and Affiliates
This course explores issues related to advanced
clinical practice, research, and education with anemphasis on specific theoretical perspectives,
methodologies, practice and economic implications.
B. Undergraduate Courses
1. First Aid & CPR (1 credit Lecturers & practice)Prof. Kanda and Affiliates
Students will understand the EMS (Emergency
Medical Services) system and learn how to act inemergency situations. The practicum includes
following subjects; 1) observation and measurement of vital signs, 2) first aid to the victim withbleeding, intoxication, or burn, 3) how to carry an
injured person, and 4) CPR (cardiopulmonary resuscitation).
2. Fundamental Nursing 1 (2 credits, Lecturers)
Prof. Kanda and Affiliates
This course offers fundamental knowledge ofnursing, such as history and theory in nursing,concepts of professional nursing practice, nursing
service and care delivery systems, nursing administration, and nursing education. Discussions
include contemporary challenging issues and future strategies in nursing.
3. Fundamental Nursing 2 (2 credits, Lecturers)
Prof. Kanda and Affiliates
This course offers fundamentals in understanding
interpersonal relationships and assessing clients'
health. Students will learn 1) theory and practicein communication, 2) knowledge necessary for
identifying health problems and care priorities, 3)
skills essential to health assessment, 4) nursing
process and nursing diagnosis, and 5) current ethical issues in nursing and health.
4. Fundamental Nursing 3 (4 credits, Lecturers andlaboratory practicum)

5.

6.

7.

8.

Prof. Kanda and Affiliates
This course provides theory and practice of fundamental nursing skills, which are essential toproviding clients with: 1) safe and effective careenvironment, 2) physiological and psychosocial
integrity, and 3) health promotion and maintenance.
Clinical Practicum in Fundamental Nursing (2credits, practice)Prof. Kanda, Staffs and Affiliates
Under instructors' supervision, students have opportunity to apply their fundamental knowledge
and skills of nursing in a variety of settings. Students will assess clients' health and needs throughapplication of nursing process.
Nursing Administration (1 credit, Lecturers)
Prof. Kanda and Affiliates
This course prepares students for nurse administrators/managers of all types of health care settings such as institutions, organizations, community and politics. Students will learn fundamental
theory and practice in nursing administration/management through analyzing current issues
in health care and nursing.
Nursing Administration Practicum (1 credit, practice)Prof. Kanda and Staffs
Students have administrative/management practicum in units or divisions in hospitals. Students
will learn care delivery systems such as staffing
and patient classification systems, nursing informatics, and budgetary issues including cost effectiveness and quality improvement.
Nursing Research (2 credits, Lecturers)
Prof. Kanda and Affiliates
This course offers examples of nursing research invarious settings. Students will learn fundamentals
of identifying problems for nursing research,measurestaken,
methodsofquantitative/qualitative data collection and analysis, andreviewing research articles in nursing and health.

Research activities
Nursing research starts with an approach to addressa variety of complex problems related to health experience of human beings' daily life. Philosophical274

orientations and research methodologies may include
natural scientific (or biomedical, quantitative, statistical) approaches, or social and human scientific (ornarrative, qualitative) approaches, or combination ofboth approaches.
1. Issues of Nursing Administration
Critical analysis and international comparative
study of administrative, socioeconomic and political issues in contemporary nursing. Focuses areon 1) patient classification systems and nursing
care delivery systems, 2) cost-effectiveness ofnursing services, 3) nursing case management,
and 4) nursing policy and strategies to meet the
professional demands.
2. Quality Improvement, Safety Issues, and Risk
Management in Nursing
This work examines 1) quality of nursing care, 2)
outcome management for nursing practice, 3) risk
management in acute care settings, 4) occupational safety and health of health care workers,
and 5) infection control.
3. Physiological and Psychological Human Responses to Stimulus
This area of study aims at exploring the nature, or
determining various effects of physiological andpsychological stimulus to participants' physiological bio-information and psychologicalmeasurements. Research scenarios include; 1)patient' daily activities, 2) caregivers' workload
and sleep deprivations, or 3) nurses focus ofattention,eyemovement,
andelectroencephalography
activities.
Data
collections take place through field studies or
4. Nursing
laboratory/experimental
Assessment and settings.
Intervention
Exploration of structure of existing discipline anddevelopment of new nursing theories in clinicalpractice. Emphases are on 1) explorations ofstructure of nursing theories and models in nursing, 2) development of clinical and scholarly
knowledge for the identification of health problems and assessment of care priorities, and 3)
testing hypotheses effective for nursing interventions
5. Studies of Nursing Education
Exploration of nursing education systems andfunctional roles of professional nurses in various

settings in advanced countries and developing
countries as well. Higher education for the advanced practice nurses in Japan is also explored.

References
1. Sasaki M, Kanda K：Glove Selection as PersonalProtective Equipment and Occupational Dermatitis among Japanese Midwives. Journal of Occupational Health 48:35-43, 2006.
2. Watanebe Y, Takemura Y, Sasaki M, Kanda K.
The relationship between working environment
and nursing practice. Japanese Journal of Nursing
Administration, 16:653-658, 2006. (in Japanese)
3. Lee JS, Kanda K, Watanuki S, Yano M. Databasefor quality management of medical and nursing
services in Norway. Japanese Journal of Nursing
Administration, 16:72-77, 2006. (in Japanese)
4. Watanuki S, Kanda K, Lee JS, Yano M. Danish
national program to improve quality of healthcare:
Healthcare quality improvement activities by useof the result of the clinical indicator survey. Japanese Journal of Nursing Administration,
16:152-157, 2006. (in Japanese)

275

Department of Family Nursing
Professor
Associate Professor
Kiyoko Kamibeppu, R.N., P.H.N., Ph.D.

Lecturer
Akemi Yamazaki, R.N., R.M., P.H.N., Ph.D.

Associate
Noriko Matsui, R.N., P.H.N., M.H.S.,

Homepage

Shiho Ozeki, R.N., R.M., M.S.

http://park.itc.u-tokyo.ac.jp/fn/

Introduction and Organization

Research

This Department was established in 1992. The Japanese Association for Research in Family Nursing was
founded by this department in 1994. Currently, it has
four faculty members; an associate professor, a lecturer and two associates.

Topics of our current research projects are as follows:
1. Psychological upset and psychological preparation of children undergoing minor surgery
2. Psychosocial factors related to symptom management of children with cancer
3. Studies of Post Traumatic Stress Disorder (PTSD)
and other late effects among survivors of childhood cancer
4. The development of an instrument measuring thequality of life for children
5. Qualitative research to explore childbearing family formation process
6. Postnatal depression and difficulties in childrearing
7. A study of mourning work in the family bereaved
children
8. Families/siblings of children with chronic illness
9. Activities of nurses in child care centers
10. Mental health of Japanese high school students

Education
1. Graduate Courses, School of Health Sciences andNursing
Advanced Family Nursing I
Advanced Family Nursing II
Laboratory and/or Field Work on Family
Nursing
2. Undergraduate Courses, School of Health Sciences and Nursing
Family Nursing
Pathophysiologic Immunology
3. Undergraduate Courses of Nursing, School of
Health Sciences and Nursing
Pediatric Nursing
Clinical Practicum in Pediatric Nursing
4. Undergraduate Courses of Midwifery, School of
Health Sciences and Nursing
Midwifery III.

Publications
1. Kamibeppu K. Clinical psychologist in General
Hospitals – Focusing on consultation-liaison psychology. Japanese Journal of Clinical Psychology.

276

2.

3.

4.

5.

6.

7.

8.

2006;6(1):14-9. (in Japanese)
Kamibeppu K. Childhood cancer and PTSD. The Japanese Journal of Child Nursing. 2006;29(12):1637-1641.
(in Japanese)
Kamibeppu K, Sato I, Hoshi Y. The narratives of adolescents after losing siblings to pediatric cancer: a qualitative
analysis. 2006;21:13~27. (in Japanese)
Matsui N, Sugai Y. Systematic Review of Accidental
Falls in Institutional Settings in Japan. Japanese
Journal of Geriatric Psychiatry. 2006;17(1):65-74.
(in Japanese)
Wakimizu R, Kamibeppu K. Review of Literature:
Effects of psychological preparation of pediatriccare in Japan. Journal of Japanese Society ofChild Health Nursing. 2006;15(2):82-89. (in Japanese)
Wakimizu R, Kamibeppu K. Effects on emotional
upset in hospitalized pediatric surgery patients ofrepeated viewing of a promotional video at homeprior to hospitalization: a randomized controlled
trial. Iryo to Shakai. 2006;16(2):183-202. (inJapanese)
Wakimizu R, Kuroki H, Igarashi M. Literature
review of physician-patient relationship in pediatric primary care. The Journal of Ambulatory andGeneral Pediatrics. 2006;9:24-32. ( in Japanese)
Onda K, Kamibeppu K, Sugimoto Y. Mothers’
Experiences during end-of-life care at home forchildren with cancer. Journal of Japanese Societyof Child Health Nursing. 2006;15(2):39-45. (inJapanese)

277

Department ofCommunity Health Nursing
Public Health Nursing
Professor
Sachiyo Murashima, D.H.S., R.N., P.H.N.

Lecturer
Satoko Nagata, D.H.S., R.N., P.H.N.

Associate
Atsuko Taguchi, M.H.S., R.N., P.H.N.

Homepage

http://park.itc.u-tokyo.ac.jp/chn/

Introduction and Organization
Department of Community Health Nursing was established in June 1992. Department of Public HealthNursing was established related to opening of mastercourse for public health nurses in 2006. At present,
there are three faculty members introduced above and
16 graduate course students (11 in master course, 5 indoctoral course) in the department. Also, we accept
many visiting researchers from other colleges and institutions.

Teaching activities
1. Undergraduate program, in the School of Health
Sciences and Nursing
1) Community Health Nursing (4 credits, lectures)
Community health nursing is a study to develop
the caring techniques and the method to evaluate the effectiveness of care not only for a person but also for a whole community. This
class is to study , the concepts and functions ofcommunity health nursing, developing processof community health nursing, community assessment and activities of community healthnurses.

2) Community Health Nursing Practice (3 credits,
practice)This program is intended to understand the system of health promotion and prevention by attending the actual community health nursing
activities. Students are expected to realize theprinciple and the common technique of community health nursing activities by observing
the activities of public health nurses.
3) Geriatric Community Health Nursing (2 credits,
lectures)
The aim of this class is to have a deep understanding of the social context around the elderly
and the medical, health and welfare system.
Also, students attend the nursing practice at avisiting nurse station to understand the homecare.
4) Health Guidance (2 credits, lectures)This class is to study the methodology andpractice of health guidance, which is the supporting technique to promote health of the people living in the community
2. Graduate program, in the Graduate School of
Health Sciences and Nursing
1) Advanced Community Health Nursing I (2 cre-

278

dits, lectures)This program is to study the health at the community-level and theory and application of thecommunity organization.
2) Advanced Community Health Nursing II (2credits, lectures)This program is to study the research issues onhome care and methodology of qualitative research for community health nursing.
3) Advanced Public Health Nursing I (2 credits)
This program is to study the methodology ofcommunity assessment for advanced community health nursing practice using the textbook
for master course students in western countries.
4) Advanced Public Health Nursing II (2 credits)
This program is to understand policymaking of
national and local government, method to operate and evaluate the systems, and approach topolicy development as public health nurses
through lectures by experts of public policy andsocial welfare.
5) Advanced Community Health Nursing Seminar
I, II (4 credits)
Student participate one of the projects which
encourage their study and promote their ability.
6) Field Work on Advanced Community HealthNursing I, II (4 credits)
In addition to these programs, we have department meeting (journal reading and research introduction) on every Tuesday, and monthly seminar on every 3rd Friday.

Research activities
Our research focuses on the development and evaluation of health care programs, establishment ofcommunity health care systems, and standardizationof skills of public health nurses, in response to thehealth care needs of individuals, families, aggregates
and the communities. We are conducting researches
on Grant-in-Aid for Scientific Research of Ministry of
Education, Culture, Sports, Science and Technology,
Health Science research Grants of Ministry of Health,Labour and Welfare, and grants from some foundations.
Research projects which are undergoing in our de-partment are listed below.
1. Developing activity model of public health nurse
and terminology of community health nursing
We intend to standardize the terms used in community health nursing and develop the activity
model for community health nursing (primarily
for public health nurses). Through review andbrainstorming, we will systematize the terms
which explain the activity of public health nurses,
develop the activity model, and verify the validityof the model.
2. Skills of public health nurses
For the purpose of health maintenance and improvement of the community residents, publichealth nurses provide services (i.e. “personal
support”) to each resident and family with healthproblems. On the other hand, they play a role todevelop new services to provide more effective
and efficient support to more residents with samekinds of problems and influence the administrative decision. These activities are called “development of program,” which lately had been recognized as an important function of public healthnurses. We are conducting researches to clarify
the techniques used by the public health nurse’s inprogram development.
3. Establishment and evaluation of community
health care systems
The project has been designed to reform service
systems and currently being evaluated. The
around- the-clock in-home care system and discharge planning system are examples of these researches which are now being conducted.
Furthermore, we are conducting the research topromote community organization and interorganizational network.
Especially about the around-the-clock in-homecare system, through the model project at visiting
nurse services stations, we clarify the effects ofthe services and the methods to establish the system. Also we are developing and validating thecheck sheet to detect the patients who have thepotential need of visiting nurse services.

279

4. Expansion and enforcement of visiting nursing
activities
We are conducting researches to develop and expand the field of visiting nurse services, throughthe model projects to deliver the visiting nurse
services to group-homes for elderly, and to findand encourage the role of visiting nurse service
stations in rural and remote areas.
5. Discharge planning
Discharge planning is an interdisciplinary processthat should be available to aid patients and theirfamilies in developing a feasible plan for the next
place of care, and there is an increasing demandfor it. We are trying to standardize dischargeplanning activities, to develop the outcome indicator of discharge planning, and to produce theeducational program of discharge planning forward nurse. And we are conducting the research
about discharge planning system.
6. Support for families with babies and children
We are conducting researches covering two fields,
community health and occupational health. For
example, we compare the work-family conflicts ofworking mothers and fathers with small children
in order to reduce their stress and burden. Also,
the network for childrearing was investigated to
avoid child abuse.
7. Support for people with diseases or disabilities
We are making researches for people with diseases or disabilities to improve their QOL.
The research themes in 2006 are 1) Acceptance todiseases and experiences in hospitalization for
multidrug-resistant tuberculosis patients and 2)
Strategies of childhood cancer survivors to continue working.

References
1. Yoshioka-Maeda K，Murashima S，Asahara K
Tacit knowledge of public health nurses in identifying community health problems and the need for
new services:multiple case study. International
Jounal of Nursing Studies. 2006; 43: 819-826.
2. Yoshioka-Maeda K，Taguchi A， Murashima A，

3.

4.

5.

6.

7.

8.

et al. Function and practice of public health nursing in Japan: a trial to develop the Japanese Purpose-Focused Public Health Nursing Model.
Journal of Nursing Management. 2006; 14:483-489.
Watai I, Nishikido N, Murasima S. Developmentof a Japanese Version of the Work-Family Conflict
Scale (WFCS), and Examination of its Validity
and Reliability. Journal of Occupational Health.
2006; 48: 71-81. (Japanese)
Watai I, Nishikido N, Murasima S. Review ofwork-family conflict study: Focused on Japansese
workers. Occupational Mental Health. 2006; 14:
199-206. (Japanese)
Murayama H, Taguchi A, Murashima S. Development of Satisfaction and Burden scales forcommunity activities of health promotion volunteers. Japanese Journal of Public Health. 2006; 53:
875-883. (Japanese.)
Murayama H, Taguchi A, Murasima S. Related
factors to the Attitude toward Community of
Health Promotion Volunteers by Years of Experience. Journal of Japan Academy of Community
Health Nursing. 2007; 9; 24-31. (Japanese)
Arimoto A，Murashima S. Child-rearing Anxiety
and Its Correlates Among Japanese Mothers
Screened at 18-month Infant Health Checkups.
Public Health Nursing. 2007; 242: 101-110.
Arimoto A．Public Health Nursing against Child
Abuse and Neglect: Reviews of Japanese andEnglish Research Papers Published between 1996
and 2006. Journal of Japan Academy of Community Health Nursing. 2007; 9: 37-45. (Japanese)

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Department of Adult Nursing /Palliative Care Nursing
Professor
Keiko Kazuma, R.N., Dr.Hlth.Sci.

Associate
Mitsunori Miyashita, R.N., Dr.Hlth.Sci.
Naomi Ito, R.N., Dr.Hlth.Sci.
Makoto Tanaka, R.N., Dr.Hlth.Sci.

Homepage http://www.adng.m.u-tokyo.ac.jp/
Introduction and Organization
The Department of Adult Nursing / Palliative Care
Nursing originated as the “Department of Adult
Health” in the School of Health Sciences (1965-1992),
later becoming the “Department of Adult Health andNursing” in the School of Health Sciences & Nursing(1992-).
From 1995 to 1997, the Graduate School of Medicine shifted to a Graduate School chair system, andour two newest departments were established. The
members of these two departments cooperate in educational and research projects.
Our department takes charge of the Advanced Nurse
Course (Transplantation Nursing) newly established in2006.

Teaching activities
In undergraduate courses, our departments have thechair of Lecturer and school- and hospital-based practicums in adult nursing. In addition, our departments
have the educational responsibility of teaching students about “disease in adult populations I and II”,
which is a basic discipline for adult nursing.
In graduate courses, the two departments cooperatein education and research. In particular, during thefirst term of the doctoral course (master’s course), in

which students learn basic research skills, the focus ison the effective and efficient management of bothfields.
Graduate students prepare their dissertations by
developing research question from their own scientificinterests or by participating in departmental projects.
Since we consider that the process itself is a part ofthe educational training of researchers, we focus ourenergy on seminars for developing master’s and doctoral theses.

Research activities
Our department conducts research on adult nursing
from various points of view. One such perspective
focuses on the course of a disease, in which not only
the periods of recovery and terminal treatment but
also the upstream preventive steps, before disease onset, are assessed with the chronic phase in the center;
therefore, such nursing comprises an extremely wide
range of periods of practice. We have been conducting
studies which are expected to allow us to understandthe state of individuals who require nursing in those
periods, and investigations on effective and efficientnursing care for such individuals.
Another theme regarding nursing systems is how
care should be provided for individuals in the mostappropriate ways. We have been investigating how

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nursing should be provided, and the continuity ofnursing care in various settings, such as outpatient
clinics, at home, and in palliative care facilities, by
focusing on individuals before disease onset, in thechronic phase, in the recovery period, and in the terminal period. We consider that it is essential to eliminate and/or improve the difficulties nurses in thesesettings must confront, since they are associated with
the improvement of care; therefore, such issues havealso been investigated.
Furthermore, one of our research themes is the development of evaluation measures and scales, which
are required in such studies.
Herein, we describe our current research areas. You
may refer to our homepage for more information, suchas the details of our research achievements, and theacquisition of research funds. The resources that havebeen developed in our research, such as evaluation
scales, are freely available to the public via our homepage.
1) Nursing for Patients with Chronic Illnesses
It is necessary for individuals with chronic illnesses
to conduct self-management for symptom control intheir daily lives. Nursing has the important role ofsupporting patients to maintain their lifestyle by continuing self-management in their daily life.
We have developed various instruments for measuring the difficulties that patients with chronic illnesses experience in their daily lives, and have described actual situations of difficulties using these
instruments. Furthermore, we have conducted a study
regarding support for controlling symptoms in order toreduce such difficulties.
The summaries of these studies, including sometheses in preparation for publication, are briefly described below.
Diabetes (DM): We have developed a scale for eating behaviors associated with QOL, and investigatedthe QOL-associated factors. We have conducted arandomized clinical trial (RCT) for an efficacy verification and economic evaluation of nursing support(individual nursing consultation) for the improvementof blood sugar control in collaboration with the Department of Diabetes and Metabolic Diseases at the
University of Tokyo Hospital. We are developing preventive strategies for adult offspring of diabetes pa-

tients.
Cardiovasular diseases: We have a developed andvalidated Japanese version of the European Heart
Failure Self-Care Behavior scale and investigated thefactors associated with self-care behavior. Furthermore, a follow-up study, evaluating the influence ofthe self-care on the rehospitalization, is conducted. We
are on the process of developing a Japanese version of
the coronary revascularisation outcome questionnaire.
Inflammatory intestinal diseases: As ulcerative colitis (UC) and Crohn’s disease (CD) occur in young
patients, and tend to relapse, long-term support for
symptom control is required. We have developed ascale for assessing perceptions of daily life difficulties
among UC patients, investigated the factors associatedwith the difficulties, and obtained suggestions for reducing such difficulties. Regarding CD, a one-year
follow-up investigation was conducted with a focus on
eating habits as a factor associated with relapse.
Bone and joint diseases: Regarding chronic rheumatoid arthritis, we investigated patients’ actual practice of exercising at home for symptom control andrelated factors. Regarding coxarthrosis (hip osteoarthritis), we described the QOL and difficulties
experienced by patients who did not have operations,and investigated associated factors. Currently, we areconducting a survey on a wider range of subjects, including patients who had operations.
Physical activities of the elderly: We have developed and verified the validity and reliability of a Japanese version of a physical activity measurement scalethat was developed in the United States. This study
was conducted as a part of a Japan and Korea collaboration with contributions from members of theSeoul National University. Using this scale, the actual
condition of physical activities of Japanese elderly
was described, and related factors were identified.
2) Promotion of Patients’ Adaptation following Gastrointestinal Surgeries
Resection and reconstruction of gastrointestinal
tracts are the main procedures used in cancer treatment, and are also used for other diseases, such as UC.
A postoperative problem is the occurrence of physical
impediments due to resection and reconstruction. The
role of nurses includes supporting patients’ adaptive
behaviors following a surgical procedure, and at-282

tempting to reduce the physical impediments the patients experience as much as possible.
We have developed a scale for assessing thelife-stability perceptions of life stability in patients,
who required a permanent stoma due to cancer. We
suggested that the factors improving the perceptionsof stability included “frequency of visits to stoma care
outpatient clinics,” and “receiving support fromnurses.” We are currently conducting a longitudinal
study regarding the life-stability perceptions of individuals with stoma using this scale.
For patients with UC, during internal medical
treatment, intake of lipids is limited. Since the limitation becomes unnecessary after total extirpation of thelarge intestine, the possibility of excess intake of lipids due to extreme changes in diet, and developmentof symptoms due to the surgery emerge; however, noinvestigation had been conducted on these issues.
Therefore, we conducted a detailed patient survey regarding diet, postoperative symptoms, and coping behaviors (eating behaviors to reduce symptoms) following total extirpation of the large intestine.
3) Nursing for Recipients and Donors in Advanced
Medicine (organ transplantation)
In a transplantation therapy in advanced medicine,both recipients and donors experience various difficulties, which have not been observed in conventional
medicine. Reduction of such difficulties is also important in nursing. The University of Tokyo Hospitalis a medical facility that provides one of the highest
levels of treatment in living donor liver transplantation and bone marrow transplantation in the world.
Therefore, we are currently conducting the following
studies on cases at the hospital:
We have described the QOL of patients who underwent adult living donor liver transplantation, andthe experiences of donors before and after transplantation. In addition, we initiated a study regarding difficulties in the chronic stage following bone marrowtransplantation and support for reducing such difficulties.
4) Nursing Care System for Outpatients
Recently, the role of nursing in hospital outpatientcare and home care has changed dramatically due tothe decrease in the duration of hospitalization, the in-crease of chronic diseases, and the increase of the elderly population. In the field of adult nursing, we focus on consultation and guidance in outpatient care inorder to support self-management of chronic diseases.
We have performed a nation-wide survey, and havebeen conducting educational activities regarding thepromotion of nursing activity in outpatient care.
Regarding diabetes, which is predicted to rapidly
increase in prevalence in the near future, we have clarified the current prevalence and problems regarding
nursing support in outpatient clinics across Japan. We
have also established protocols for consultation andguidance in outpatient care, and are promoting themfor use in medical facilities across Japan.
Regarding HIV/AIDS, we have been promoting
collaboration on nursing support for reinforcing patients’ drug adherence with other facilities, and areattempting to spread these consultation and guidance
activities across Japan.
5) Evaluation of Specialized Palliative Care and Quality Assurance
Palliative care services in Japan are primarily provided by palliative care teams in general wards, inpalliative care units, and at home. We have conducted
research on methods for evaluating palliative careservices by focusing on various categories, such as
symptom control and communication. We have developed a Japanese version of the STAS-J, which is anevaluation scale developed in the U.K., and are attempting to promote its utilization. We have participated in the development of a care evaluation scale forbereaved families. Furthermore, we are conducting asurvey on the current status of palliative care teams,
and research regarding the evaluation. We are alsostrongly motivated to evaluate palliative care for patients with hematological cancers, which remain uncommon in Japan.
6) Continuity of the Palliative Care System
End-stage cancer patients receive care in generalwards, palliative care units, and at home. We haveconducted a study on the preparation of a system fortransition in the care setting. Actual research goals
include the identification of preference in care settings
and related factors, and the factors that facilitate asmooth transition from general wards or palliative

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units to the patient’s home.
7) Good Death in Japan
Recently, the conceptualization of good death,
which is one of the goals of palliative care, and investigations of the current status are being conducted inWestern countries. We have conceptualized good
death in Japan by conducting qualitative research,followed by quantitative research, on groups comprised of the general public and bereaved families.
Our next step is to establish intervention measures byinvestigating the attainment of good death and possible barriers. We also consider that it is important toprovide education for the general public.
8) Palliative Care at HomeA large number of patients wish to receiveend-stage care at home; however, many difficulties are
involved in the realization of such requests. Thus, it is
one of the most important problems in palliative carein Japan.
We have conducted a study regarding the actualcare provided at home based on a survey of patientsand their families, and a study that described and evaluated the experiences of bereaved families who attended the home death.
9) The Field of Basic Preparation for Nursing Research
We have been continuously conducting investigations on the tasks associated with nursing researchmethodology, and the nursing terms that are the foundation for the establishment of the field of nursing.

References
1. Kazuma K, Hagiwara A, Ito N, Sawai K. Development of the Japanese version of Physical Activity Scale for the Elderly (PASE) and explorationof the factors related to physical activities of theelderly in Japan. Transactions of the second invited seminar, research on physical activity innursing; 2006 Jul 7; Seoul, Korea; 2006. p.3-11.
2. Kazuma K. Measurement of health related QOL. J
Fam Tumor. 2006;6(2):58-61. (in Japanese)

3. Takeda Y, Kazuma K, Gondo N, Iwama T. Parents'
perception of familial adenomatous polyposis. J
Fam Tumor. 2006;6(2):45-52.
4. Miyashita M, Hashimoto S, Kawa M, Shima Y,
Kawagoe H, Hase T, Shinjo Y, Suemasu K. Attitudes towards disease and prognosis disclosureand decision-making for terminally ill patients inJapan, based on a nationwide random sampling
survey of the general population and medical
practitioners. Palliat Support Care. 2006; 4:
389-98.
5. Miyashita M, Yamaguchi A, Kayama M, Narita Y,
Kawada N, Akiyama M, Hagiwara A, Suzukamo
Y, Fukuhara S. Validation of the Burden Index of
Caregivers (BIC), a multidimensional short careburden scale from Japan. Health and Quality ofLife Outcomes. 2006; 4:52.
6. Morita T, Miyashita M, Shibagaki M, Hirai K,
Ashiya T, Ishihara T, Matsubara T, Miyoshi I,
Nakaho T, Nakashima N, Onishi H, Ozawa T,
Suenaga K, Tajima T, Akechi T, Uchitomi Y.
Knowledge and beliefs about end-of-life care andthe effects of specialized palliative care: A population-based survey in Japan. J Pain Symptom
Manage. 2006; 31(4):306-16.
7. Hirai K, Miyashita M, Morita T, Sanjo M, Uchitomi Y. Good death in Japanese cancer care: A
qualitative study. J Pain Symptom Manage. 2006;
31(2): 140-147.
8. Morita T, Hyodo I, Yoshimi T, Ikenaga M, Tamura
Y, Yoshizawa A, Shimada A, Akechi T, Miyashita
M, Isamu Adachi and for the Japan Palliative
Oncology Study Group. Artificial hydration therapy, laboratory findings, and fluid balance in terminally ill patients with abdominal malignancies.
J Pain Sympotm Manage. 2006;31(2): 130-139.
9. Miyashita M, Kawa M. The nursing role for theartificial hydration for the terminall ill cancer patient. The Japanese Journal of Nursing Art. 2006;
52(6): 47-9. (in Japanese)
10. Miyashita M, Sasahara T. Clinical audit in thehospital based palliative care team. The Japanese
Journal of Hospice and Palliative Care. 2006;
8(2): 111-8. (in Japanese)
11. NishigakiM, Kobayashi K, Shibayama T, Kadowaki T, Kazuma K. Attitude of diabetes care specialists to prevention of diabetes to relatives of284

patients with Type 2 diabetes. Journal of the Japan
Diabetes Society. 2006;49(8):669-676. (in Japanese)
12. Tada M, Kaneko S, Imamura Y, Sobue T. Importance of casefinding in a standardized hospital-based cancer registry system for regional Ministry-designated cancer care hospitals. Medical
record administration. 2006; 17(3): 27-32. (inJapanese)
13. Koyama Y, Miyashita M, Kazuma K, Suzukamo Y,
Yamamoto M, Karita T, Takatori Y. Preparing a
version of the Nottingham Adjustment Scale (forpsychological adjustment) tailored to osteoarthritis of the hip. J Orthop Sci. 2006 Jul;11(4):359-64.
14. Higuchi H, Sasahara T. Profile and recognition ofphysicians working within a certified hospital-based palliative care team in Japan. Symptoms
Management in Cancer Patients. 2006; 17(1):75-84. (in Japanese)
15. Hasegawa K, Sasahara T, Oyagi Y, Toya M, Kawachi K, Takahashi M, Akaba S, Kondo M, Kosako F, Iba N, Umeda M. The role of nurse in
hospital-based palliative care team〜The result of
focus group interview〜. The Japanese Journal of
Hospice and Palliative Care. 2006; 6(4): 365-370.
(in Japanese)
16. Nakai Y, Miyashita M, Sasahara T, Koyama Y,
Shimizu Y, Kawa M. Factor strudture and reliability of Japanese version of the Frommelt attitudes
toward care of the dying scale (FATCOD-B-J).
Japanese Journal of Cancer Nursing. 2006; 11(6):723-9. (in Japanese)

285

Department of Midwifery and
Women's HealthProfessor
Sachiyo Murashima, Ph.D., R.N., P.H.N.
(Concurrent office: Community Health Nursing)

Lecturer
Megumi Haruna, Ph.D., R.N., R.M., P.H.N.
Ryoko Murayama, MS., R.N., R.M.

Associate
Etsuko Watanabe, MS., R.N., R.M., P.H.N.

Homepage

http://park.itc.u-tokyo.ac.jp/midwifery/index.html

Introduction and Organization
The Department of Midwifery and Women’s Healthwas established in 2002.
Currently, it has 4 faculty members introduced
above and 6 part-time lecturers, 4 graduate students (2in master course, 2 in doctoral course), and one research student.

Teaching activities
We teach graduate and undergraduate courses for
midwifery and maternal care, and women's health.
1. Graduate Courses, School of Health Sciences andNursing1) Advanced Midwifery and Women’s Health 1 (2credits, lectures)
2) Advanced Midwifery and Women’s Health 2 (2credits, lectures)
2. Undergraduate Courses of Nursing, School of
Health Sciences and Nursing
1) Maternity Care and Nursing(2 credits, lectures)
2) Maternity Care and Nursing Practice(2 credits, practice)
3. Undergraduate Advanced Courses for Midwifery,
School of Health Sciences and Nursing1) Midwifery 1 (1 credit, lectures)
2) Midwifery 2 (1 credit, lectures)
3) Midwifery 4 (3 credits, lectures)
4) Administration for Midwifery(1 credit, lectures)
5) Clinical Practice of Midwifery 1(1 credit, practice)6) Clinical Practice of Midwifery 2(7 credits, practice)

Research activities
Our research activities focus on maternal-childhealth care as well as health promotion and quality oflife of women in each life cycle.
Current research projects are as follows.
1) Life style and oxidative stress during pregnancy
2) Maternal body composition during pregnancy andinfant birth weight3) Nutrition and weight management during pregnancy and postpartum

2864) Quality of sleep and sleeping posture of women5) Promotion of women’s health care after delivery
and during menopause
6) Application of the ICF (International Classificationof Functioning Disability and Health) to an assessment of quality of life among pregnant women

References
1. Haruna M, Murashima S, Nagata S, Taguchi A.
Impact of the introduction of the long-term careinsurance system in Japan on public health nurses.
Journal of Japan Academy of Community HealthNursing 2006; 9:47-52.
2. Matsuzaki M, Haruna M, Ota E, Watanabe E,
Murayama R, Tsukamoto H. Urinary biopyrrin as
a possible oxidative stress marker during pregnancy. Journal of Japan Academy of Midwifery
2006; 20:40-49.
3. Kubota T, Murayama R, Kogure T. Investigating
the influence of porous mattress upon the comfort
level of sleep. Bulletin of Saitama Occupational
Therapy 2005; 6:34-37.
4. Kogure T, Kubota T, Murayama R. The relationship between the air permeability of the mattressand the bed climate. Japanese Journal of Physiological Anthropology 2007; 12:37-42.
5. Ueda Y, Maruo M, Nakano H, Honda Y, Miyama
T. Nutritional assessment by estimating maternal
weight gain and fat mass during pregnancy. Diabetes & Pregnancy 2006; 6:96-103.
6. Ueda Y, Maruo M, Nakano H, Honda Y, Miyama
T, Nishizawa M, Heymsfield S B. Estimation ofbody fat mass in pregnant women by a new method using bioelectrical impedance analysis withcompensation for intrauterine component weight.
International Journal of Body Composition Research 2006; 4:145-152.

287

Department of
Psychiatric Nursing
Professor
Norito Kawakami, M.D., Ph.D.

Lecturer
Yuki Miyamoto, R.N., P.H.N., P.S.W., Ph.D.

Homepage

http://plaza.umin.ac.jp/heart/

Introduction and Organization
Our department was firstly established as Department of Fourth Clinical Medical Nursing in School of
Health Care and Nursing in 1957. When the School of
Health Care and Nursing was reorganized as the
School of Health Sciences in 1965, the department
was renamed Department of Mental Health. In 1992,
as School of Health Sciences became The School of
Health Science and Nursing, Department of Mental
Health became Department of Mental Health andPsychiatric Nursing. As the result of the shift to thechair system of the Graduate School of Medicine in
1996, two departments were established, Departmentof Mental Health and Department of PsychiatricNursing. Faculty, staff, and students of two departments have been working cooperatively ever since.
Our department currently has two faculty members
introduced above, part-time lecturers, visiting research
fellows, 5 doctoral course students, 3 master course
students, and research associates.
Our department’s mission comprises two elements.
One is to provide education and research training inmental health and psychiatric nursing to undergraduate and graduate students in order to prepare students
to assume leadership roles in nursing clinical practice,administration, teaching, and research in this field.
The other is to conduct clinical research in the fieldsof psychiatric nursing and advance knowledge andtheory through research.
All of the activities of our department are con-ducted in collaboration with staff members in the Department of Mental Health.

Teaching activities
Our department is responsible for giving lectures on
psychiatric nursing to undergraduate students. Other
than lectures, our department provides students opportunities to practice psychiatric nursing activities inseveral relevant facilities.
Our department is also obliged to educate graduate
students in master and doctor programs in psychiatricnursing. To accomplish this objective, our department
has a specialized lecture course on psychiatric nursing,and seminars on mental health and psychiatric nursing
for graduate students. These activities are conducted
and supervised by the faculty. In collaboration withthe department of mental health, we also have the department seminar every Wednesday evening, where
members provide the actual plans for their own research introduce relevant articles already publishedand discuss the topic. Also, prominent guest speakers
give lectures from time to time in this seminar.
We also have monthly journal clubs and study
clubs.

Research activities
Our research field covers mental health and psychiatric nursing. Our department has many research projects across diverse fields as follows: study of com-

288

munity support system for the people with mental
health needs; issues of caregiver burden in family caregivers; psychiatric clinical pathways; behavioral andpsychological symptoms of dementia; patient satisfaction with psychiatric services; practice and evaluationof home visiting psychiatric nursing; illness
self-management in mental health; and recovery forpeople with mental illness. We are conducting studies
in collaboration with researchers in other institutions
and universities.

References
1.

2.

3.

4.

5.

6.

7.

Miyashita M, Yamaguchi A, Kayama M, Narita Y,
Kawada N, Akiyama M, Hagiwara A, Suzukamo
Y, Fukuhara S: Validation of the Burden Index of
Caregivers (BIC), a multidimensional short careburden scale from Japan. Health and Quality ofLife Outcomes. 2006; 4:52.
Funakoshi A, Miyamoto Y, Kayama M: Managerial Support of Community Mental Health Nurses.
Journal of Advanced Nursing (in press) .
Setoya N, Oshima I, Makino H, Sawada A, Cho
N, Fukui S, Oka I, Yoshida K, Ikebuchi E, Ito J:
Development of ʻReadiness for Participationto
Psychoeducation Scale (RPPS)ʼ for people withschizophrenia: reliability and validity [in Japanese]. Seishin Igaku.. 2006; 48(2): 135-143.
Wada K, Satoh T, Tsunoda M, Aizawa Y, and The
Japan Work Stress and Health Cohort Study
Group: Associations of health behaviors on depressive symptoms among employed men in Japan. Industrial Health. 2006; 44: 486-492.
Sawada A, Porter S, Kayama M, Setoya N, Miyamoto Y. Nursing care delivery in Japanese
psychiatric units. British Journal of Nursing.
2006; 15(17):920-925
Takao S, Tsutsumi A, Nishiuchi K, Mineyama S,
Kawakami N. Effects of the job stress education
for supervisors on psychological distress and job
performance among their immediate subordinates: A supervisor-based randomized controlled
trial. Journal of Occupational Health. 2006; 48:494-503.
Funakoshi A, Miyamoto Y, Kayama M. Visiting
nurse service station managersʼ recognition of
the difficulties experienced by staff nurses who

8.

9.

10.

11.

12.

13.

14.

15.

provide home care for people with mental illness[in Japanese]. Journal of Japan Academy of
Nursing Science. 2006; 26(3): 67-76.
Honjo K, Kawakami N, Takeshima T, Tachimori
H, Ono Y, Uda H, Hata Y, Nakane Y, Nakane H,
Iwata N, Furukawa TA, Watanabe M, Nakamura
Y, Kikkawa T. Social class inequalities inself-rated health and their gender and age groupdifferences in Japan. J Epidemiol. 2006;
16(6):223-32.
Ishizaki M, Kawakami N, Honda R, Nakagawa H,
Morikawa Y, Yamada Y; The Japan Work Stressand Health Cohort Study Group. Psychosocial
work characteristics and sickness absence inJapanese employees. Int Arch Occup Environ
Health. 2006 (in press)
Naganuma Y, Tachimori H, Kawakami N, Takeshima T, Ono Y, Uda H, Hata Y, Nakane Y, Nakane H, Iwata N, Furukawa TA, Kikkawa T.
Twelve-month Use of Mental Health Services inFour Areas in Japan: Finding from the World
Mental Health Japan Survey 2002-2003. Psychiatry and Clinical Neurosciences. 2006;
60(2):240-8.
Akiyama MO, Kayama M, Takamura S, Kawano
Y, Ohbu S, Fukuhara S. A study of the burden of
caring for patients with amyotrophic lateral sclerosis (MND) in Japan. British Journal of Neuroscience Nursing. 2006; 2(1): 38-43.
Honjo K, Tsutsumi A, Kawakami N. What accounts for the relationship between social classand smoking cessation? Results of a path analysis.
Social Science and Medicine. 2006; 62: 317-28.
Kawakami N, Takao S, Kobayashi Y, Tsutsumi A.
Effects of web-based supervisor training on job
stressors and psychological distress among
workers: A workplace-based randomized controlled trial. Journal of Occupational Health.
2006; 48: 28-34.
Kawakami N, Tsutsumi A, Haratani T, Kobayashi
F, Ishizaki M, Hayashi T, Fujita O, Aizawa Y,
Miyazaki S, Hiro H, Masumoto T, Hashimoto S,
Araki S. Job Strain, Worksite Support, and Nutrient Intake among Employed Japanese Men and
Women. Journal of Epidemiology. 2006; 16:
79-89.
Kondo K, Kobayashi Y, Hirokawa K, Tsutsumi A,289

Kobayashi F, Haratani T, Araki S, Kawakami N.
Job strain and sick leave among Japanese employees: A longitudinal study. International Archives of Occupational and Environmental
Health. 2006; 79: 213-9.
16. Funakoshi A, Kawano Y; Job satisfaction ofnurses working in acute hospitals [in Japanese].
The Japanese Journal of Mental Health. 2006;
21(2) 35-43.
17. Funakoshi A, Kayama M, Matsushita T, Yamaguchi A, Ueno R, Sawada A, Hayashi A, Miyamoto Y, Setoya N, Matsuura A, Kimura M, Akiyama M, Ito H, Amagaya T, Satake R, Sato M,
Nakano S, Hato K, Otsuka T, Fukuda T, Anbo H,
Kawano Y. Every day life skills in patients withschizophrenia who are receiving home carenursing [in Japanese]. The Japanese Journal of
Hospital and Community Psychiatry. 2006; 49(1):66-72.

290

Department ofGerontological Nursing /Wound Care Management
Professor
Hiromi Sanada, R.N., P.H.N., WOCN., Ph.D.

Lecturer
Etsuko Tadaka, R.N., P.H.N., Ph.D.

Associate
Atsuko Kitagawa, R.N., Ph.D.

Homepage

http://www.rounenkango.m.u-tokyo.ac.jp

About Us
The Department of Gerontological Nursing is thenewest department of the Health Sciences and Nursing
Division of the Graduate School of Medicine at the
University of Tokyo. From established in June 2003,
this department is headed by one professor and assisted by one lecturer, one associate professor and fivepart-time lecturers. The student body consists of ninegraduate students and three research students. Since
the establishment of this department in 2006, education and research have been our two main areas ofactivity. The basic course for undergraduates is “Evidence-based Practice for Gerontological Nursing"where we wish to create a society that respects thebeauty of aging and recognizes it to be a joyful process in life.

Education
1. Undergraduate course
1) Gerontological Nursing (3-4th yr/ 4 credits)
The aim of this 3rd year course is for students tounderstand the physical, psychological and social
characteristics of the elderly population. The main
themes in the 2006 curriculum were:a) Practical Simulation for Gerontological Nursingb) Physical, Psychological & Social Characteristicsof the Elderlyc) Social, Health and Medical Policies for a HealthyLifestyle for the Elderlyd) Long-term Care Insurance System and Caring for
the Elderlye) Understanding the Characteristics of Elderly
Illnessesf) 3 Tier Prevention of Functional Decline in the
Elderly.
The aim in 4th year is to understand the ailments
and conditions necessary to provide proper care to theelderly.
The main themes in the 2006 curriculum were:a) Pharmacologic Management of the Elderlyb) Nutritional Management of the Elderlyc) Age-related Changes in the Physiologic Systemd) Aging and Respiratory Disorders,e) Common Urinary Disorders of the Elderlyf) Cognitive Disorders of the Elderlyg) Cardiovascular Disorders of the Elderlyh) Osteoporosis of the Elderlyi) Physical Assessment of the Elderlyj) Comprehensive Geriatric Assessment and Care of
Elderly with Dementia.

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The above lectures were developed under the cooperation by the Department of Geriatric Medicine and
The University of Tokyo Hospital.
2) Clinical Practice in Gerontological Nursing(4th yr/ 3 credits )The aim of this practicum is to learn the skills essential for caring for elderly in a long-term care facility. This program was supported by the long-term carefacility owned by Medical Corporation Tatsuoka.
3) Undergraduate Thesis
Research themes in 2006 were as follows:‘Nutritional status and mutable associated factors in
the free-living elderly’’Quantitative evaluation of elderly skin based on
digital image analysis’
2. Graduate course
1) Gerontological Nursing I (Summer course/ 2
credits)
2) Gerontological Nursing II (Winter course/ 2
credits)
This program focuses on studying the latest developments related to gerontological nursing.
Gerontological Nursing I offers participants to havetheir presentations reviewed and critiqued by top researchers world-wide. In 2006, one student's work
concerning the prevention of dementia and the risk
factors in everyday life among the elderly was presented.
Gerontological Nursing II consists of lectures anddiscussion about recent themes in gerontologicalnursing. The main themes in 2006 were:a) Introduction to Geriatrics Syndromeb) Homebound Elderlyc) Dementia: A World Reportd) Issues related to the Asian Elderlye) Elderly Needs during a Natural Disasterf) Pressure Ulcers in the Elderlyg) Elderly Living Alone
3) Wound Care Management I (Summer course/ 2
credits)
4) Wound Care Management II (Winter course/ 2
credits)
This program focuses on studying the latest developments related to wound care management.

Wound Care Management I is a discussion-based
workshop aimed at learning about the latest pressure
ulcer research. D. Bader and others teach the basics ofpressure ulcer treatment to clinical applications using'Pressure Ulcer Research' (Springer-Verlag Berlin
Heidelberg, 2005).
Wound Care Management II consists of lectures anddiscussion about recent themes in wound care management. The main themes in 2006 were:a) Introduction to Skin Ulcersb) Latest Developments in Leg Ulcer Treatmentc) Foot Care for Diabeticsd) Pressure Ulcers and Nutritione) Selecting Support Surfaces for Pressure
Distributionf) Understanding the TIME concept and woundhealingg) Controlling Vascular Function by Blood Flowh) Principles of Ultrasound and Image Assessment of
Ultrasound Image Echographyi) Management and Treatment of Severe Pressure
Ulcers and Intractable Ulcersj) Wound Healing in Fetuses
5) Master’s thesis
The following was a research theme in 2006:’Interface pressure distribution of elderly Japanesepeople in the sitting position’

Research
Our main activity involves the "Evidence-based
Practice for Gerontological Nursing" where we are
striving to develop new nursing techniques and instruments to fulfill the needs of those elderly wishing
to maintain their independence.
Specifically, we are trying to improve the prediction,
prevention, diagnosis and treatment of elderly suffering with geriatric syndrome, pressure ulcers, incontinence, malnutrition, pain, depression, and dementia.
Most research is conducted under industry-academia
cooperation. We hope through this research to increase
physical activity and enhance self-esteem of the elderly in order to maintain their independent lifestyles.
In addition, consideration must be given to the various types of elderly and their specific needs. One ofour goals is to develop a program, or system that can292

allow these elderly to maintain their independent lifestyle for as long as possible.
For example, in Japan, the number of dependentelderly and those living alone is expected to increase,thus we have chosen this as our theme and taking into
consideration the environmental conditions and otherfeatures we are trying to develop a program or systemthat suits various situations.
1) The following research is being conducted todevelop new wound management techniques andinstruments to maintain or improve thephysiological functioning for the elderly:
・ Prediction and Prevention of Pressure Ulcers
・ Techniques and Instruments used in Pressure
Ulcer Management
・ Methods of Controlling Pressure Ulcers andPain2) Development of a care program evaluation system
in order to support the elderly in maintaining their
independence・ Preventive program for elderly living alone
・ Preventive program for frail elderly
・ Therapeutic care program for elderly withdementia
・ Reminiscence group care program for theelderly

References
1. Sato M, Sanada H, Konya C, Sugama J,
Nakagami G. Prognosis of stage I pressure ulcers
and related factors. Int Wound J.2006 3: 355-62.
2. Nakagami G, Sanada H, Kitagawa A, Tadaka E,
Maekawa T, Nagase T, et al. Incontinence induces
stratum corneum vulnerability and impairs theskin barrier function in the perianal region.
Dermatology. 2006 213: 293-9.
3. Suriadi, Sanada H, Sugama J, Thigpen B,
Kitagawa A, Kinosita S, et al. A new instrument
for predicting pressure ulcer risk in an intensive
care unit. J Tissue Viability. 2006 16: 21-6.
4. Okuwa M, Sanada H, Sugama J, Inagaki M,
Konya C, Kitagawa A, et al. A prospective cohort
study of lower-extremity pressure ulcer risk
among bedfast older adults. Adv Skin Wound
Care. 2006 19: 391-7.

5. Nakagami G, Sanada H, Konya C, Kitagawa A,
Tadaka E, Tabata K. Comparison of two pressure
ulcer preventive dressings for reducing shear
force on the heel. J Wound Ostomy Continence
Nurse. 2006 33: 267-72.
6. Nakagami G, Konya C, Kitagawa A, Tadaka E,
Urasaki M, Sanada H. Effect of a new pressure
ulcer preventive dressing on shear force reduction.
EPUAP Review. 2006 7: 16-7.

294

Department of
Health Policy and Planning
Associate Professor
Chushi Kuroiwa, M.D., Ph.D.

Assistant Professor
Ali Moazzam, M.D., Ph.D.

Homepage

http://www.sih.m.u-tokyo.ac.jp/index-E.html

Introduction and Organization
In the past 20 years, globalization together withmarked-oriented economy established by the Neoliberalism has been continuously gaining huge power
and the poor appear to be pushed farther away from
reaping its benefits. Besides, our planet has faced
enormous challenges such as global warming, famine,
scarcity of clean water, growing number of populationand environment degradation, which pose worrying
health risks.
Industrialized countries have developed sophisticated health policies for developing countries, yetmany issues remain when considering the sustainability. Our mission is to educate students from Asian
countries to become leaders in the field of international health and to carry out researches to address
challenges and hidden realities in health for vulnerable
people.
By pursuing alternative richness or happiness instead of economic growth, we would like to achieve
real health through respecting existing health systems,
indigenous cultures, and nature.

Previous Major Research Activities- EPI and measles control at post-polio eradication
period (International Cooperation Research Grant)- Monitoring & evaluation of multi-bi cooperation(Grant from Ministry of Health)- Problems of EPI in developing countries in Laosand Mongolia (Grant from Ministry of Education,
Science)- Monitoring & evaluation on IMCI (Integrated
ManagementofChildhoodIllness)inLaos/Mongolia (Grant from international medical
center of Japan, Ministry of Health)- Health Policy and Health-Care Waste Managementin Asia (ongoing) (Grant from Ministry of Environment)

Major Research Activities- International health policy and system analysis:
MDGs, IMCI, ODAs/NGOs, Health damages andreal poverty caused by globalization- Child Health: EPI, IMCI, Nutrition by Brest Feeding- Environment Health (Medical waste management
and international health policy, safety injection, aid
and environmental damage)- Reproductive Health. Gender (violence)- Infectious
Diseases:
Malariaprevention;
HIV/AIDS; Tuberculosis.
- Allergic Diseases and Asthma Epidemiology- Emergency Medicine

Integrated Activities
Health Policy Discussion with International Medical Center of Japan, University of Nagoya
Health projects in IMCJ and researches.

295Managing editor for BioScience Trend (International Academic journal)
Visiting professor at Public Health in Shandong
University in China.
ASNET (Asian Studies Network in University ofTokyo) lecture for master students on Asian crisis andinfectious diseases.
Board member of the NPO: International Emerging
Medicine and Health Support, Japan (IEMS Japan).
Communication with NGOs preserving environment such as Mekong Watch, Namakemono club.
Universities and research institutions in Laos,
Mongolia, Shandong and Dairen in China, Thailand,
Pakistan, etc

Department meeting
Department meeting is held every Monday (1-3pm):
1) Journal reading; 2) Presentation of research planand results; 3) reading and discussion on Bulletin of
WHO.
Open seminar on Health Policy discussion based onfield experience by guest speakers: every 3rd Monday
of each month (6-7:40pm)

Publications
1.

Education
Health Policy and Planning I and II (2 credits each)
The followings are the main topics covered in theacademic year 2007;
1. Introduction: Child survival in the world such as
IMR150 and Japan’s Health System
2. ODA in the world, Japanese aid and trend
3. World aid trend: GO, PPP, NGOs, etc
4. Policy Advocacy and Roles of Civil Society Actors – Applicability of Lessons Learnt from ODA
Reform for Health Policies
5. Infectious diseases eradication (smallpox, polio,
measles, etc) and EPI, expanded programme on
immunization
6. PKO and SDF, disaster medicine
7. Risk in Asia: Infection (global warming, emerging
diseases, bio-weapon), and medical waste
8. Risk in Asia: Health System of UN in the globalization or neoliberalism
9. Health Policy, an introduction to process andpower
10. Health sector reform, SWAP
11. Innovative Health Policy by students
12. Green revolution (game for experiencing the reality of aid world)
13. Poverty reduction, Global Fund
14. HIV, Malaria, TB control and health policy
15. Infectious disease surveillance in Japan
16. Nutrition programme and health policy

2.

3.

4.

5.

6.

7.

8.

Ali M, Kuroiwa C. Accurate record keeping inreferral hospitals in Pakistan's North West Frontier Province and Punjab: a crucial step needed to
improve maternal health. Journal of the Pakistan
Medical Association (in press).
Ozaki, Ali M, Kuroiwa C. Economic burden of
diseases and cost benefit analysis of emergency
medical service (EMS) system in Rumania. Nihon Hyoka gakkai (in press).
Phathammavong O, Ali M, Kuroiwa C. Parasitic
Infestation and Nutrintional Status among
Schoolchildren in Vientiane, Lao PDR. Journal of
Paediatrics and Child Health (in press).
Gai R, Huang Y, Xu L, Tang W, Kuroiwa C.
Strengthening national public health system on
bio-terrorism alert and response. Journal of
Pathogen Biology (in press).
Ali M, Rizwan H, Ayaz Bhatti AM, Kuroiwa C(2007). Women's rights equal women's lives: Thecase of Pakistan. Journal of International Health;22 (1):35-45.
Shirayama Y, Phompida S, Kuroiwa C, Miyoshi
M, Okumura J, Kobayashi J (2007). Maintenancebehavior and long-lasting insecticide-treated nets
(LLITNs) previously introduced into Bourapar
district, Khammouane province, Lao PDR. Public
Health; 121(2):122-129.
Takada S, Oudavong B, Kuroiwa C (2007). The
successes and challenges of the IMCI training
course in Lao PDR. Southeast Asian J Trop Med
Public Health; 28(1):178-87.
Phengxay M, Ali M, Yagyu F, Soulivanh P,
Kuroiwa C, Ushijima H (2007). Risk factors forprotein-energy malnutrition in children under 5

296

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

years: Study from Luangprabang Province, Laos.
Pediatric International; 49(2):260-265.
Tanimura S and Kuroiwa C, Mizota T (2007).
Auxilary Cartographic Functions in R: North Arrow, Scale Bar, and Label with Leader Arrow.
Journal of Statistical Software; 19 (Code Snippet
1).
Kuroiwa C, Odajima H, Oudavong B, Zhang Z,
Miyoshi M and Nishima S (2006). Prevalence ofasthma, rhinitis, and eczema among children in
Vientiane City, Lao PDR. Southeast Asian J Trop
Med Public Health; 37(5):1025-33.
Ali M, Miyoshi C, Ushijima H (2006). Emergency medical services in Pakistan: A publicprivate partnership. Public Health; 120(1):50-57.
Shirayama Y, Phompida S, Kuroiwa C (2006).
Modern medicine and indigenous health beliefs:
malaria control alongside Sadsana-phee (animist
belief system) in Laos. Southeast Asian J Trop
Med Public Health; 37(4):622-629.
Sakisaka K, Wakai S, Kuroiwa C, Cuadra Flores
L, Kai I, Hanada K (2006). Nutritional status andassociated factors in children aged 0-23 months
in Granada, Nicaragua. Public Health; 120:400411.
Gai R, Huang Y, Han J, Yao Q, Kuroiwa C, Tang
W (2006). To avoid potential threat of emerging
virus diseases for public health: An etiologicalreview of human-transmissible avian influenza.
Journal of Pathogen Biology; 1:54-7.
Gai R, Han J, Huang Y, Yao Q, Qu X, Nakata M,
Kokudo N, Sugawara Y, Makuuchi M, Kuroiwa
C, Tang W (2006). Avoiding pandemic influenza:
Improvements and concerns in China’s publichealth system. Journal of Health Care and Society; 16:139-45.
Aiga H, Kuroiwa C (2006). Quantity and distribution of continuing professional education opportunities among health workers in Ghana.
Journal of Continuing Education in Nursing; 37(6):270-9.
Tanimura S, Kuroiwa C, Mizota T (2006). Proposal Symbol Mapping in R. Journal of Statistics
Software; 15(5):1-7.
Ali M, Hotta M, Kuroiwa C, Ushijima H (2005).
Emergency obstetric care in Pakistan: Potential
for reduced maternal mortality through improved

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

basic EmOC facilities, services, and access. Gynecology & Obstetrics; 91:105-112.
Miyoshi M, B Phommasack, Nakamura S,
Kuroiwa C (2005). Nutritional status of children
in rural Lao PDR: who are the most vulnerable?
European Journal of Clinical Nutrition;59:887890.
Kuramitsu M, Kuroiwa C, Yoshida H, Miyoshi M,
Okurmura J, Shimizu H, Narantuya L, and
Bat-Ochir D (2005). Non-polio enterovirus isolation among families in Ulaanbaatar and Tov
province, Mongolia: prevalence, intrafamilial
spread, and risk factors for infection. Epidemiology and Infection;133:1131-1142.
Hansman G, Kuramitsu M, Yoshida H, Katayama
K, Takeda N, Ushijima H, Surenkhand G, Gantulga D, and Kuroiwa C (2005). Viral Gastroenteritis in Mongolian Infants. Emerging Infectious
Disease; 11(1):180-183.
Phengxay P, Okumura J, Miyoshi M, Sakisaka K,
Phengxay M, Kuroiwa C (2005). Health carewaste management in Lao PDR: A case study.
Waste Management & Research; 23:571-581.
Kuroiwa C, Suzuki A, Yamaji Y, Miyoshi M(2004). Hidden reality on the introduction of
auto-disable syringes in developing countries.
South Asian J Trop Med Public Health; 35(4):1019-1023.
Ali M, Shahab S, Ushijima H, de Muynck A(2004). Street children in Pakistan: A situational
analysis of social conditions and nutritional status.
Social Science and Medicine; 59(8): 1707-17.
Ali M, Ushijima H (2004). Emerging role of theprivate sector in HIV/AIDS disease prevention in
Pakistan. Tropical Doctor; 34(3):189-90.
Ali M, Rizwan H, Ushijima H (2004). Men andreproductive health in rural Pakistan: the case forincreased male participation. European Journal ofContraceptive and Reproductive Health; 9:260266.
Kuroiwa C, Xayyavong P, Vongphrachanh P,
Khampapogpane B, Yamanaka M, Nakamura S(2003). Difficulties in measles elimination:
prevalence of measles antibodies before and after
mass vaccination campaign in Laos. Vaccine; 21:479-484.
Kuroiwa C (2002). Flawed analysis of limited

297

29.

30.

31.

32.

33.

data led to an incorrect conclusion that a measles
immunization campaign in the Lao People's Democratic Republic had minimal impact, author
reply. J of Epidemiology; 12(4):342-343.
Ali M, Horikoshi Y (2002). Situation analysis ofhealth management information systems in Pakistan. Pakistan Journal of Medical Research; 41(2):64-69.
Kuroiwa C, Vongphrachanh P, Xayyavong P,
Southalack K, Hashizume M, Nakamura S (2001).
Measles epidemiology and outbreak investigation
using IgM test in Laos. Journal of Epidemiology;
11(6):255-262.
Chiba Y, Kuroiwa C (2001). [Collaboration between JICA projects and other projects (e.g. international organizations, local NGOs)]. In: A
Handbook on international health and medical
cooperation. International Medical Center of Japan eds., International Development Journal; 4043.
Kuroiwa C, Vongphrachnh P, Chosa T, Murakami
H, Hashizume M, Wakai S, Tanaka M (2000).
Risk of Poliomyelitis importation and reemergence in Laos. Lancet; 356:1487-88.
Kuroiwa C, Chosa T, Murakami H, Duangmala S,
Vongphrachanh P, Saito T, Chiba Y (1999). Polio
Surveillance in Lao PDR: A two-year experienceof active case search, 1994-1996. Journal of
Tropical Pediatrics; 45:185-190.

298

Department of International
Community HealthProfessor
Masamine Jimba, MD, PhD, MPH

Assistant Professor
Krishna C. Poudel, PhD, MHSc
Junko Yasuoka, DSc, MPH
Kayako Sakisaka, PhD

Homepage

http://www.ich.m.u-tokyo.ac.jp

Introduction and Organization
The department of international community healthhas been headed by four professors since 1993; Professors Gen Oi (1993-1996), Som-Arch Wongkhomthon (1996-1999), Susumu Wakai (1999-2005), andMasamine Jimba (2006-present).
The mission of the department is to seek equity andsocial justice in health within and across the nations.
Our aim is to bring together the clinical, public healthand social science research to address the broad issuesof pubic health in the world. The goals are to:
1. Investigate how to improve health status of themost vulnerable people, in particular, in developing countries,
2. Undertake research on the influences of ‘globalization’ and ‘free market’ system on health andsocial development,
3. Investigate the mechanisms to reduce inequalities
between and within nations on health and development.
The organization of the department is as follows:
Professor (1), Assistant Professors (3), Visiting Lecturers (6), PhD course students (12), Master’s course
students (16), Research students (6), and Visiting researchers (16).

International Cooperation
Activities
Our department has conducted a variety of international cooperation activities through JICA andnon-governmental organizations. The target countries
have been Nicaragua, Lao PDR, Cambodia, Thailand,
Vietnam, and Brasil. In particular in Cambodia, wehave worked together with the Ministries of Healthand Education as well as WHO, UNESCO and completed a comprehensive school health policy at a national level.

Teaching Activities
The objectives of our teaching activities are summarized as follows.
1. Train those who are willing to work for international cooperation in future,
2. Train those who are willing to contribute to carryout research in international health,
3. Teach general students who are interested in international health.
The major topics for teaching is as follows: 1) Whatis international health? 2) Health promotion in developing countries, 3) Health economics, 4) Research
ethics, 5) Project management, 6) Reproductive health
Our department has accepted students of various disciplines: medical doctors, nurses, co-medical workers,social scientists and others. The academic year of

299

Master Course (MA, 2 years) and Doctor Course (PhD,
3 years) starts in April and ends in March every year.
All the lectures and seminars are conducted in English.

Research activities
We have carried our research by working together
with different international organizations, NGOs,
universities in developing countries. The major focusof research has been primary health care, health promotion, school health, health and human rights (including migrants’ health), conflict and health, injury
prevention, HIV/AIDS, tuberculosis, leprosy, etc. The
target countries have been those in South Asia, South
East Asia, Nicaragua and Brasil. The outcomes of ourresearch are listed in the next section.

References
1. Poudyal AK, Jimba M, Silwal RC, Murakami I,
Sherchand JB, Wakai S. Targeting newly enrolled
low-age school children for the control of the intestinal helminth infection in rural Nepal. TropDoct. 2006; 36: 16-9.
2. Okabayashi H, Thongthien P, Singhasvanon P,
Waikagul J, Looareesuwan S, Jimba M, Kano S,
Kojima S, Takeuchi T, Kobayashi J, Tateno S.
Keys to success for a school-based malaria control
program in primary schools in Thailand. Parasitol
Int. 2006; 55: 121-6.
3. Nakahara S, Poudel KC, Lopchan M, Ichikawa M,
Poudel-Tandukar K, Jimba M, Wakai S. Availability of childcare support and nutritional status ofchildren of non-working and working mothers inurban Nepal. Am J Hum Biol. 2006; 18: 169-81.
4. Sakisaka K, Wakai S, Kuroiwa C, Cuadra Flores L,
Kai I, Mercedes Aragon M, Hanada K. Nutritional
status and associated factors in children aged 0-23
months in Granada, Nicaragua. Public Health.
2006; 120: 400-11.
5. Ichikawa M, Nakahara S, Wakai S. Cross-culturaluse of the predetermined scale cutoff points in
refugee mental health research. Soc Psychiatry
Psychiatr Epidemiol. 2006; 41: 248-50.
6. Hashizume M, Kondo H, Murakami T, Kodama M,
Nakahara S, Lucas ME, Wakai S. Use of rapid

diagnostic tests for malaria in an emergency situation after the flood disaster in Mozambique. Public Health. 2006; 120: 444-7.
7. Ichikawa M, Nakahara S, Wakai S. Effect of
post-migration detention on mental health among
Afghan asylum seekers in Japan. Aust N Z J Psychiatry. 2006; 40: 341-6.
8. Jimba M. New professionalism in the 21st century.
Lancet. 2006; 367: 648-9.
9. Uetani M, Jimba M, Kaku T, Ota K, Wakai S. Oral
health status of vulnerable groups in a village of
the Central Highlands, southern Vietnam. Int J
Dent Hyg. 2006; 4: 72-6.
10. Jimba M, Sakisaka K, Hanada K. Aid for Africa:
listen to women leaders. Lancet. 2006; 367: 1729.
11. Aikawa R, Jimba M, Nguen KC, Zhao Y, Binns
CW, Lee MK.Why do adult women in Vietnam
take iron tablets? BMC Public Health. 2006; 6:
144.
12. Poudel-Tandukar K, Nakahara S, Ichikawa M,
Poudel KC, Wakai S. Relationship between
mechanisms and activities at the time of pedestrian injury and activity limitation among school
adolescents in Kathmandu, Nepal. Accid Anal
Prev. 2006; 38: 1058-63.
13. Poudel-Tandukar K, Nakahara S, Ichikawa M,
Poudel KC, Joshi AB, Wakai S. Unintentional injuries among school adolescents in Kathmandu,
Nepal: a descriptive study. Public Health. 2006;
120: 641-9.
14. Silwal RC, Jimba M, Poudyal AK, Poudel KC,
Wakai S. Improving immunization services under
the armed conflict in rural Nepal. Public Health.
2006; 120: 805-8.
15. Poudel KC, Jimba M, Okumura J, Wakai S.
Emerging co-infection of HIV and hepatitis B virus in far western Nepal. Trop Doct. 2006; 36:
186-7.
16. Poudel KC, Jimba M, Wakai S. AIDS and humanrights research. Trop Doct. 2006; 36: 191-2.
17. Uetani M, Jimba M, Niimi T, Natsume N, Katsuki
T, Xuan le TT, Wakai S. Effects of a long-term
volunteer surgical program in a developing country: the case in Vietnam from 1993 to 2003. Cleft
Palate Craniofac J. 2006; 43: 616-9.
18. Nakahara S, Ichikawa M, Wakai S. Magazine information on safety belt use for pregnant women

300

and young children. Accid Anal Prev. 2007; 39:356-63.
19. Joshi AB, Banjara MR, Bhatta LR, Rikimaru T,
Jimba M. Assessment of IDD problem by estimation of urinary iodine among school children.
Nepal Med Coll J. 2006; 8: 111-4.
20. Poudel KC, Poudel-Tandukar K, Jimba M.
HIV/AIDS vulnerability of Nepali migrants to India: whose concern? Lancet. 2006; 368: 1648.
21. Jayatilleke A, Poudel KC, Jimba M. Intimate-partner violence. Lancet. 2006; 368: 1765.
22. Kobayashi J, Jimba M, Okabayashi H, Singhasivanon P, Waikagul J. Beyond deworming: thepromotion of school-health-based interventions by
Japan.
Trends Parasitol. 2007; 23: 25-9.
23. Poudel KC, Jimba M, Poudel-Tandukar K, Wakai
S.Reaching hard-to-reach migrants by letters: an
HIV/AIDS awareness programme in Nepal.
Health Place. 2007; 13: 173-8.
24. Iriyama S, Nakahara S, Jimba M, Ichikawa M,
Wakai S.AIDS health beliefs and intention forsexual abstinence among male adolescent students
in Kathmandu, Nepal: a test of perceived severity
and susceptibility. Public Health. 2007; 121:
64-72.
25. Fujiya R, Jimba M, Giacaman R, Nakahara S,
Ichikawa M, Wakai S. The influence of economic
factors on the location of birth among Palestinian
women in Bethlehem during the second Palestinian uprising. Trop Doct. 2007; 37: 13-7.
26. Kanamori S, Jimba M. Compensation for avian
influenza cleanup. Emerg Infect Dis. 2007; 13:341-2.
27. Nomura Y, Poudel KC, Jimba M. Hard-to-reach
populations in Japan.
Southeast Asian J Trop Med Public Health. 2007;
38:325-7.
28. Jimba M, Aitken IW, Joshi AB, Ohashi T, Poudyal
AK, Wakai S.A challenge for monitoring iodine
deficiency disorders in rural Nepal. Trop Doct.
2007; 37:106-7.
29. Singh S, Sharma SP, Mills E, Poudel KC, Jimba
M.Conflict induced internal displacement in Nepal. Med Confl Surviv. 2007; 23:103-10.
30. Aikawa R, Jimba M, Nguen KC, Binns
CW.Prenatal iron supplementation in rural Viet-nam. Eur J Clin Nutr. (In press)
31. Poudel KC, Poudel-Tandukar K, Yasuoka J, Jimba
M. HIV superinfection: another reason to avoid
serosorting practice. Lancet (In press).
32. Poudel-Tandukar K, Nakahara S, Ichikawa M,
Poudel KC, Jimba M. Risk perception, road behavior and pedestrian injury among adolescentstudents in Kathmandu, Nepal. Inj Prev. (Inpress).

302

Department of Human Genetics
Professor
Katsushi Tokunaga, Ph.D.

Associate Professor
Naoyuki Tsuchiya, M.D., Ph.D. (- September 2006)

Associate
Jun Ohashi, Ph.D., Hiroko Miyadera, Ph.D.

Homepage

http://www.humgenet.m.u-tokyo.ac.jp/

Introduction and Organization
The Department of Human Genetics was established in 1992. Currently, the department has one professor, one associate professor, two associates, 17
graduate students, 6 research fellows, and 9 research
assistants/technicians. We also accept a few graduate
students from Clinical Departments for their PhD studies.

Teaching activities
For students at the Graduate School of International
Health, courses that cover basic principles as well as
the clinical application of human genetics are provided.
As to undergraduate students, a series of lectures isgiven to each of the sophomore (Human Genetics I,
compulsory) and junior (Human Genetics II, elective)classes at the School of Health Sciences. A series oflectures is also provided to the first year (M0) students
at the School of Medicine (compulsory).

Research activities
The Department of Human Genetics is broadly interested in the human genome diversity, especially in
the Asian populations. Specifically, we are using genomic research tools including SNP and microsatellite
analyses, as well as gene expression profiling, to bet-

ter understand the genetic background of a variety ofcomplex diseases, especially autoimmune diseases,
infectious diseases and sleep disorders.
Major research projects:
1) Theoretical and experimental analyses on the genetics of complex diseases, including the development of statistical approaches for susceptibility
gene mapping in complex diseases, genomic studies for the understanding of genetic backgroundand pathogenesis of autoimmune diseases, sleep
disorders, hypertension, diabetes, as well as forhost susceptibility factors to infectious diseases.
2) Development of new methodologies for genome
polymorphism and gene expression analyses.
3) Analysis on the genome diversity of Asia-Pacificpopulations.
4) Development of methodologies for the analysis ofprotein interactions.

References
1. Li S-L, Yamamoto T, Yoshimoto T, Uchihi R, Mizutani M, Kurimoto Y, Tokunaga K, Jin F, Katsumata Y, and Saitou N: Phylogenetic relationship of
the populations within and around Japan using 105
short tandem repeat polymorphic loci. Hum. Genets 118(6): 695-707, 2006.
2. Xinh PT, Vu HA, Nghia H, Binh NT, Be TV, Binh
TV, Tokunaga K, and Sato Y: Coexistence ofPhiladelphia chromosome positive cells with andwithout der(9) deletion in a patient with chronic

303

myelogenous leukemia. Cancer Genet. Cytogenet.
164(2): 122-127, 2006.
3. Shi L, Xu SB, Ohashi J, Sun H, Yu JK, Huang XQ,
Tao YF, Yu L, Horai S, Chu JY, and Tokunaga K:
HLA-A, B and DRB1 alleles and haplotypes in
Naxi and Han populations in southwestern China(Yunnan province). Tissue Antigens 67(1): 38-44,
2006.
4. Yoshiura K, Kinoshita A, Ishida T, Ninokata A,
Ishikawa T, Kaname T, Bannai M, Tokunaga K,
Sonoda S, Komaki R, Ihara M, Saenko V, Alipov
G, Sekine I, Komatsu K, Takahashi H, Nakashima
M, Sosonkina N, Mapendano C, Ghandami M,
Nomura M, Liang DS, Miwa N, Kim DK, Garidkhuu A, Natsume N, Ohta T, Tomita H, Kaneko
A, Kikuchi M, Russomando G, Hirayama K, Ishibashi M, Takahashi A, Saitou N, Murray J, Saito S,
Nakamura Y, and Niikawa N: A SNP in the
ABCC11 gene is the determinant of human earwax type. Nature Genet. 38(3): 324-330, 2006.
5. Doi K, Noiri E, Nakao A, Fujita T, Kobayashi S,
Tokunaga K: Functional polymorphisms in thevascular endothelial growth factor gene are associated with development of end-stage renal disease in males. J. Am.Soc. Nephrol. 17(3): 823-830,
2006.
6. Miyashita R, Tsuchiya N, Yabe T, Kobayashi S,
Hashimoto H, Ozaki S, and Tokunaga K: Association of killer cell immunoglobulin-like receptor(KIR) genotypes with microscopic polyangiitis.
Arthritis Rheum. 54(3): 992-997, 2006.
7. Okaji Y, Tsuno NH, Kitayama J, Sakurai D, Tsuchiya N, Saito S, Takegami K, Tsuchiya T, Kawai
K, Yazawa K, Asakage M, Yoneyama S, Yamada J,
Tokunaga K, Takahashi K, and Nagawa H: Effectsof down-regulating the Id genes in human colorectal cancer cells on early steps of haematogenous metastasis. Eur. J. Cancer 42(5): 668-673,
2006.
8. Doi K, Noiri E, Fujita T, and Tokunaga K:
No-association of VEGF genetic polymorphisms
in promoter - 5' UTR with end-stage renal disease.
Nephrol. Dial. Transplant. 21(4): 1124-1125,
2006.
9. Hirayasu K, Ohashi J, Kashiwaase K, Takanashi
M, Satake M, Tokunaga K, and Yabe T:
Long-term persistence of both functional alleles atthe leukocyte immunoglobulin-like receptor A3(LILRA3) locus suggests balancing selection.
Hum. Genet. 119(4): 436-443, 2006.
10. Horikoshi M, Hara K, Ohashi J, Miyake K, Tokunaga K, Ito C, Kasuga M, Nagai R, and Kadowaki
T: A polymorphism In the AMPKα2 subunit geneis associated with insulin resistance and type 2
diabetes in the Japanese population. Diabetes 55(4): 919-923, 2006.
11. Hara K, Horikoshi M, Kitazato H, Ito C, Noda M,
Ohashi J, Froguel P, Tokunaga K, Tobe K, Nagai
R, Kadowaki T: Hepatocyte nuclear factor-4{alpha} P2 promoter haplotypes are associatedwith type 2 diabetes in the Japanese population.
Diabetes 55(5): 1260-1264, 2006.
12. Sato-Takeda M, Takasaki I, Takeda K, Sasaki A,
Andoh T, Nojima H, Shiraki K, Kuraishi Y, Hanaoka K, Tokunaga K, and Yabe T: Major histocompatibility complex haplotype is associatedwith postherpetic pain in mice. Anesthesiology
104(5): 1063-1069, 2006.
13. Noguchi E, Ohtsuki Y, Tokunaga K, Yamaoka-Sageshima M, Ichikawa K, Aoki T, Shibasaki
M, and Arinami T: ADAM33 polymorphisms areassociated with asthma susceptibility in a Japanese population. Clin Exp Allergy. 36(5): 602-608,
2006.
14. Ohashi J, Naka I, Kimura R, Tokunaga K, Yamauchi T, Natsuhara K, Furusawa T, Yamamoto R,
Nakazawa M, Ishida T, and Ohtsuka R: Polymorphisms in the ABO blood group gene in three
populations in the New Georgia group of the Solomon Islands. J. Hum. Genet. 51(5): 407-411,
2006.
15. Ohnishi Y, Tokunaga K, Kaneko K, and Hohjoh
H: Assessment of allele-specific gene silencing by
RNA interference with mutant and wide-type reporter alleles. J RNAi Gene Silencing 2(1): 154160, 2006.
16. Xinh PT, Vu HA, Van Man H, Tri NK, Binh NT,
Nghia H, Trong PQ, Van Binh T, Van Be T, Tokunaga K, Sato Y*: Unique secondary chromosomal
abnormalities are frequently found in the chronic
phase of chronic myeloid leukemia in southern
Vietnam. Cancer Genet Cytogenet. 168(1): 59-68,
2006.
17. Shiina T, Ota M, Shimizu S, Katsuyama Y, Ha-304

shimoto N, Takasu M, Anzai T, Kulski J, Kikkawa
E, Naruse T, Kimura N, Yanagiya K, Watanabe A,
Hosomichi K, Kohara S, Iwamoto C, Umehara K,
Meyer A, Wanner V, Sano K, Macquin C, Ikeo K,
Tokunaga K, Gojobori T, Inoko H, and Bahram S:
Rapid evolution of MHC class l genes in primates
generates new disease alleles in man via Hitchhiking diversity. Genetics 173(3): 1555-1570,
2006.
18. Vu HA, Xinh PT, Masuda M, Motoji T, Toyoda A,
Sakaki Y, Tokunaga K, and Sato Y: FLT3 is fused
to ETV6 in a myeloproliferative disorder withhypereosinophilia and a t(12;13)(p13;q12) translocation. Leukemia. 20(8): 1414-1421, 2006.
19. Kawashima M, Tamiya G, Oka A, Hohjoh H, JujiT, Ebisawa T, Honda Y, Inoko H, and Tokunaga
K: Genome-wide association analysis of humannarcolepsy and a new resistance gene. Am. J.
Hum. Genet. 79(2): 252-263. 2006.
20. Ohashi J, Naka I, Tokunaga K, Inaoka T, Ataka Y,
Nakazawa M, Matsumura Y, and Ohtsuka R: Mitochondrial DNA variation suggests extensive
gene flow from Polynesian ancestors to indigenous Melanesians in the northwestern Bismarck.
Am. J. Phys. Anthrop. 130(4): 551-556, 2006.
21. Dechkum N, Hananantachai H, Patarapotikul J,
Ohashi J, Krudsood S, Looareesuwan S, and Tokunaga K: Monocyte chemoattractant protein 1(MCP-1) gene polymorphism Is not associatedwith severe and cerebral Malaria in Thailand. Jpn.
J. Infect. Dis. 59(4): 239-244, 2006.
22. Tochigi M, Zhang X, Ohashi J, Hibino H, Otowa
T, Rogers M, Kato T, Okazaki Y, Kato N, Tokunaga K, and Sasaki T: Association study of thedysbindin (DTNBP1) gene in schizophrenia fromthe Japanese population. Neurosci. Res. 56(2):154-158, 2006.
23. Ohashi J, Naka I, Toyoda A, Takasu M, Tokunaga
K, Ishida T, Sakaki Y, and Hohjoh H: Estimationof the species-specific mutation rates of the DRB1
locus in human and chimpanzee. Tissue Antigens
68(5): 427-431, 2006.
24. Nakajima F, Tokunaga K, and Nakatsuji N: HLA
matching estimations in a hyprothetical bank ofhuman embryonic stem cell lines in the Japanese
population for use in cell transplantation therapy.
Stem Cells 25(4): 983-985, 2006.

25. Ohashi J, Naka I, Kimura R, Tokunaga K, Nakazawa M, Ataka Y, Ohtsuka R, Inaoka T, and Matsumura Y: HLA-DRB1 polymorphism on Ha’ano
Island of the Kingdom of Tonga. Anthrop. Sci.
114(3): 193-198, 2006.

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Department of Developmental
Medical Sciences
Professor
Masashi Mizuguchi, M.D., Ph.D.

Associate
Masaaki Oda, Ph.D., Shoko Okitsu-Negishi, M.D., Ph.D.

Homepage
Introduction and Organization
Founded in 1996 as the Department of Maternal andChild Health, our department was the first one established in Japan. With the subsequent expansion of research activities and the foundation of the Graduate
School of Medicine, it was renamed in 1992 as the
Department of Developmental Medical Sciences. Up
to now, it has been engaged in experimental and epidemiologic studies to provide the scientific bases for
all the activities to promote the physical and mental
health of mothers and children. The experimental studies include those on the nervous and endocrine systems, infection, immunity and metabolism, whereas
the epidemiologic studies deal with development,
mother-to-child relationship and health promotion. In
2007, joined by new members, the department has justentered a new era, putting more emphasis than ever on
the research on developmental disorders of the nervous system.
At present, our department consists of one professor,
one associate professor, two associates, one clerk,
eleven visiting lecturers, eight visiting researchers,
eighteen graduate students (twelve of them are fromabroad) and three research fellows.
Our department gives lectures to undergraduate andpostgraduate students, have weekly meetings of thewhole department and of individual research groups,
communicate with other investigators inside or outside the University of Tokyo, and have seminars andmeetings with researchers invited from abroad.

We have collaborated with many laboratories in the
United States, Canada, Germany, Greece, China,
Thailand, Viet Nam, Malaysia, Bangladesh, Korea,
Taiwan, Pakistan, Sri Lanka and Russia, in order topromote the mothers’ and children’s health all over theworld. We also have accepted many young students
from these countries, for the purpose of bringing up
professionals who either perform medical research orlead local health policies.

Teaching activities
1. Undergraduate course, Faculty of Medicine, Schoolof Health Science and Nursing1) Human growth and development
2) Medical microbiology and zoology
3) Maternal and child diseases
4) Immunology
5) Maternal and child health6) School health and nursing7) International health
2. Graduate course, the Graduate School of Medicine,
School of International Health Sciences
In addition to lectures and laboratory courses by ourown staff, special lectures are given by experts both
inside and outside the University.

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Research activities(1) Molecular pathologic studies on developmental
brain disorders: Abnormal neuronal differentiation and size control in tuberous sclerosis.
(2) Molecular genetic and cell biologic studies combined with post-genomic approaches on molecules regulating neuronal migration, such as
Doublecortin and Cdk5.
(3) Studies of inflammation, cell death and plasticity
in perinatal brain damage.
(4) Clinical, genetic and pathologic studies of acuteencephalopathies: Acute necrotizing encephalopathy and acute encephalopathy with febrile
convulsive status epilepticus.
(5) Molecular genetics and biochemistry of inheritedmetabolic disorders, such as peroxisomal disorders, and of neurodegenerative diseases, such as
spinal muscular atrophy.
(6) Epidemiologic studies on nutrition (breast feeding) and child growth, and on care of infants.
(7) Molecular epidemiology of infectious diseases,in particular viral diarrheal diseases.
(8) Epidemiology and molecular genetics (epigenetics) of the fetal origin of adult diseases.
(9) Studies on immune responses using componentsof Bordetella pertussis.
(10) Effects of high-rise living on physical and mental
development of children.
(11) Studies to improve health education at schools.
(12) Studies on the health of mothers and children ofminority races.
(13) Studies on the mental health of schoolchildren,and of mothers and children living abroad

References
1. Ali M, Miyoshi C, Ushijima H. Emergency medical services in Islamabad, Pakistan: a public-private partnership. Public Health 2006;120(1):50-7.
2. Huy TT, Ushijima H Sata T, Abe K. Genome characterization of HBV genotype E in Bolivia: genotype F subgenotypes correlate with geographic
distribution and T(1858) variant. Arch Virol
2006;151(3):589-97.
3. Huy TT, Ishikawa K, Ampofo W, Izumi T, Naka-

jima A, Ansah J, Tetteh JO, Nii-Trebi N, Aidoo S,
Ofori-adjei D, Sata T, Ushijima H, Abe K. Characteristics of hepatitis B virus in Ghana: fulllength genome sequences indicate the endemicity
of genotype E in West Affica. J Med Virol 2006;
78(2):178-84.
4. Yoshinaga M, Phan TG, Nguyen TA, Yan H,
Yagyu F, Okitsu S, Muller WEG, Ushijima H.
Changing distribution of group A rotavirus
G-types and genetic analysis of G9 circulating inJapan. Arch Virol 2006;151(1):183-92.
5. Khamrin P, Peeracome S, Wongsawasdi L, TonusinS, Sornchai P, Maneerat Y, Khamwan C,
Yagyu F, Okitsu S, Ushijima U, Maneekarn N.
Emergence of human G9 rotavirus with an
exceptionally high frequency in children admitted
to hospital with diarrhea in Chiang Mai, Thailand.
J Med Virol 2006;78(2): 273-80.
6. Imura M, Misao H, Ushijima H. The psychological effects of aromatherapy-massage in healthy
postpartum mothers. J Midwifery Womens Health2006;51(2):e21-7.
7. Muller WE, Ushijima H, Batel R, Krasko A, Borejko A, Meller IM, Schroder HC. Novel mechanism for the radiation-indeuced bystander effect:
Nitric oxide and ethylene determine the responsein sponge cells. Mutat Res 2006;597(1-2):62-72.
8. Kawata K, Li Y, Liu H, Zhang XQ, Ushijima H.
Specific factor for prenatal lead exposure in theborder area of China. Int J Hyg Environ Health2006;209:377-83.
9. Phan TG, Kuroiwa T, Kaneshi K, Ueda Y, Nakaya
S, Nishimura S, Yamamoto A, Sugita K, Nishimura T, Yagyu F, Okitsu S, Müller WEG, Maneekarn N, Ushijima H. Changing Distribution of
Norovirus Genotypes and Genetic Characterization of Recombinant GIIb among Infants andChildren with Diarrhea in Japan. J Med Virol.
2006;78(7): 971-8.
10. Phan TG, Yagyu F, Kozlov V, Kozlov A, Okitsu S,
Müller WEG, Ushijima H. Viral gastroenteritis
and Genetic Characterization of Recombinant
Norovirus among Infants and Children with Diarrhea in Eastern Russia. Clin Lab 2006;52 (5-6):
247-53.

307

11. Phan TG, Yan H, Li Y, Okitsu S, Müller WEG,
Ushijima H. Novel Recombinant Norovirus in
China. Emerg Infect Dis. 2006;12(5):857-8.
12. Phan TG, Okitsu S, Müller WEG, Kohno H, Ushijima H. Identification of Novel Recombinant Sapovirus in Japan. Emerg Infect Dis. 2006;12(5):865-7.
13. Schroder HC, Boreiko A, Koizhev M, Tahir MN,
Tremel W, Eckert C, Ushijima H, Muller IM,
Meller WE. Co-expression and functional interaction of silicatein with galectin: Matrix-guided
formation of siliceous spicules in the marine demosponge suberites domuncula. J Bio Chem
2006;281(17):12001-9.
14. Khamrin P, Maneekern N, Peerakome S, Yagyu F,
Okitsu S, Ushijima H. Molecular characterizationof a rare G3P[3] human rotavirus reassortantstrain reveals an evidence for human-animals
multiple interspecies transmissions. J Med Virol
2006;78(7):986-94.
15. Phan TG, Trinh OD, Yagyu F, Sugita K, Okitsu S,
Muller WEG, Ushijima H. Outbreak of sapovirus
infection among infants and children with acutegastroenteritis in Osaka City, Japan during during
2004-2005. J Med Virol 2006;78(6):839-46.
16. Schroeder HC, Breter HJ, Fattorusso E, Ushijima
H, Wiens M, Steffen R, Batel R, Mueller WEG.
Okadaic acid, an apoptogenic toxin for symbiotic/
parasitic toxic Annelids in the Demosponge Suberites domuncula. Appl Environ Microbiol 2006;
72:4907-16.
17. Okame M, Akihara S, Hansman G, hainan Y,
Thien Tuan Tran H, Phan TG, Yagyu F, Okitsu S,
Ushijima H. Existence of multiple genotypes associated with acute gastroenteritis during 6-year
survey of norovirus infection in Japan. J Med Virol 2006;78(10):1318-24.
18. Phan TG, Shimizu H, Okitsu S, Maneekarn N,
Ushijima H. Human adenovirus type 1 related tofeline adenovirus: evidence of interspecies transmission. Clin Lab 2006;52 (9-10):515-8.
19. Phan TG, Takanashi S, Kaneshi K, Ueda Y, Nakaya S, Nishimura S, Sugita K, Nishimura
T,Yamamoto A, Yagyu F, Okitsu S, Ushijima H.
Detection and genetic characterization of norovirus strains circulating among infants and children
with acute gastroenteritis in Japan during

2004-2005. Clin Lab 2006;52 (9-10):519-25,.
20. Phan TG, Yan H, Khamrin P, Quang T, Dey SK,
Yagyu F, Okitsu S, Mueller WEG, Ushijima H.
Novel intragenotype recombination in sapovirus.
Clin Lab 2006;52(7-8):363-6.
21. Okitsu-Negishi S, Okame M, Shimizu Y, Phan TG,
Tomaru T, Kamijo S, Sato T, Yagyu F, Mueller
WEG, Ushijima H. Detection of norovirus antigens from recombinant virus-like particles andstool samples by a commercial norovirus enzyme-linked immunosorbent assay. J Clin Microbiol 2006;44(10):3784-6.
22. Ozeki N, Ushijima H, Knowles A, Asada Y. Analyses of transcultural stress factors and the mental
well-being of female foreign residents in Japan. J
Jpn Soc Psychosom Obstet Gynecol 2006;
11(2):141-51,.
23. Maneekarn N, Khamrin P, Chan-it W, Peerakome
S, Sukchai S, Pringprao K, Ushijima H. Detectionof rare G3P[19] porcine rotavirus strains in
Chiang Mai, Thailand provides evidence for theorigin of VP4 genes of Mc323 and Mc345 humanrotaviruses. J Clin Microbiol 2006;44:4113-4119.
24. Fukuoka H, Tsukamoto H. Maternal nutrition including fetal imprinting for future health and disease. J Korean Nutr 2006:34(Suppl 1);19-20.
25. Tsukamoto H, Fukuoka H, Inoue K, Koyasu M,
Nagai Y, Takimoto H. Restricting weight gain
during pregnancy in Japan:A controversial factor
in reducing perinatal complications．Eur J Obstet
Gynecol Reprod Boil 2006 Epub ahead of print.
26. Takimoto H, Sugiyama T, Fukuoka H, Kato N,
Yoshiike N. Maternal weight gain ranges for optimal fetal growth in Japanese women. Int J Gynecol Obstet 2006;92:272-8.
27. Kim CS, Park DH, Fukioka H. Observation ofbone metabolic turnover in the rats after prolonged swimming training. Contemporary Issues
in the Pacific Rim 2006;1(2):75-82.
28. Ogawa T, Furochi H, Mameoka M, Hirasaka K,
Onishi Y, Suzue N, Oarada , Akamatsu M, Akima
H, Fukunaga T, Kishi K, Yasui N, Ishidoh K, Fukuoka H, Nikawa T. Ubiquitin ligase gene expres-308

sion in healthy volunteers with 20-day bedrest.
human muscle ubiquitin ligase expression. Muscle
Nerve 2006;34(4):463-9.
29. Oda, M. Maternal transmission of infection andimmunity to infants. Health Sci 2006;48:876-81.
30. Oda, M. Effects of super high-rise living on childhealth. Architect Urban Planning 2006;344:10-3.
31. Oda, M. Natural environment in my childhood. J
Assoc Child Envir 2006;2:27-9.

309

Department of Human Ecology
Professor
Chiho WATANABE, D. Hlth Sc.

Associate Professor
Masahiro UMEZAKI, Ph.D.

Associate
Taro YAMAUCHI, Ph.D.
Hana SHIMIZU, Ph.D.

Homepage

http://www.humeco.m.u-tokyo.ac.jp/index-e.html

Introduction and Organization
We had four research/teaching faculties in FY2006.
Apart from the faculty staffs, a project research associate (Hongwei JIANG, Ph.D.), two secretaries, two
doctoral candidates (including one foreign student),
five master course students (including one foreign
students), and three research fellows are working in
the department. There are nine extra-university lecturers delivering lectures in either graduate or undergraduate course.

Teaching activities
The department is one of the six departments of the
School of International Health. Human Ecology Special Lecture I focused on the basic components of
Human Ecology such as demography, nutrition, andenvironment. In “Human Ecology Special Lecture II”,emphases were on recent topics and ongoing researches in the field of Human Ecology and relatedareas. With these classes for the Graduate Students,
we tried to describe Human Ecology as a basic component of International Health, and gave examples of
the recent issues that have been dealt with and approaches used in this field. The lectures for the Graduate Course were given in English.
In the undergraduate course, the department is incharge of a part of the School of Health Sciences andNursing, providing the lectures on “Human Ecology”,“Environmental Health”, “Demography”, “International Health”. We were also responsible for organizing “Pharmacology and Toxicology”, “Physiology”,“Anatomy”, as well as “Environmental Engineering/
Human Engineering”．At the undergraduate level, ouremphases were in introducing global-scale issues suchas population explosion, food security, and environmental issues in relation to the problems that
Asia-Pacific region (including Japan) has been facing.
Another emphasis was on the relation between humanactivities and chemical contamination of the environment.

Research activities
Most of our researches fell into the field of “Environmental Health” and/or “Population ecology [ofhuman]”, and we utilized both fieldwork and experimental approach. Most of our study fields were
Asian-Oceanian rural communities, focusing on population, nutrition/growth, and environment. Experimental studies focusing on the effects of perinatal exposures to heavy metals have been conducted, emphasizing the factors that modify the effects. What follows is a list of major projects conducted in the past
two years.
1. Neurodevelopmental effects of perinatal exposure

310

to environmental chemicals:
Modern human societies, regardless developed ordeveloping, consume and are exposed to a variety ofchemical substances, which would be regarded as a
substantial part of the environment. Since often thefetus/newborn is relatively sensitive to these chemical
substances, we focused the exposure to chemicals
during perinatal period. Collaborating with several
institutes/universities, we have conducted studies on
the effects of heavy metals (mercury and cadmium),toxicity of which were still being debated in Japan andother countries, as well as of so called endocrine disrupting chemicals. Toxicity was evaluated at cellular
as well as organism levels, and major findings included susceptibility of metallothionein knock-out
mice to the neurodevelopmental toxicity of metals,
and demonstration of developmental neurotoxicity of
low-dose of cadmium. Another experimental study
regarding the interaction between selenium and arsenic was conducted, hinted by our field study finding;effects of thyroid hormones as well as mutual modification of the kinetics were found.
2. Evaluation and Alleviation of Environmental
Burden due to Subsistence Transition in
Asia-Pacific –Elucidation of Health Impact:
Most communities in Asia-Pacific undergo a very
rapid transition from traditional subsistence to casheconomy agriculture. Such transition entails introduction and release-accumulation of chemical substances,such as pesticides and food additives (through thepurchase of processed foods), into the local ecosystem,
which in turn would affect not only the health andsurvival of the inhabitants, but also the safety of local
produce. In this study, choosing six regions that represent diversified environments in Asia-Pacific, wewill (1) describe such transition and their environmental consequences in detail, (2) investigate the interrelationship between the transitions and the changesof local chemical environments, and (3) examine theirhealth impact among the individuals in the target areas.
Final goal of the study will be to make a policy recommendation to minimize unnecessary adverse effectsof such transition.
3. Development and subsistence activity, subsistencetransition and adaptation:

In many Asian and Oceanean countries, various
types of developmental projects have been undertaken
aiming at economic development, procurement of
natural resources, or accelerating tourism. Such developmental projects brought about drastic changes inthe subsistence activity of people, availability of natural resources, or ecosystem, and in turn, causedchanges in lifestyle and health status, disease patternsof the people. Attempts to describe such changes weremade in China as well as Solomon Islands. Adaptive
strategy at household level was analyzed in China,
where subsistence transition has been taking place,and possible determinant of the difference in thestrategy was identified. In some studies, Geographical
Information System (GIS)/GPS was used for analyzing the relationship between the subsistence transitionand land-use.
4. Studies on nutrition, growth, and physical activities (energetics) in developing countries:
Nutrition is one of the fundamental requirement for
health and is especially important in developing countries.
In rural Bangladesh, food consumption, nutritional
status, and activity of the villagers were examined;
distinct gender-related difference was found.
In rural Western Java, Indonesia, the relationshipbetween the nutritional status during the preadolescentperiod and biological parameters at birth were analyzed. In Tonga, where the prevalence of obesity ishigh, anthropometry was conducted for adolescent
girls, and factors associated with obesity were identified.
In the schoolchildren of rural China, prevalence of
the infection with schistosomiasis was examined andthe relative importance of the parasite infection andnutritional status for the physical growth of the children was evaluated.
5. Water and air quality and health in developing
countries:
In many Asian and Latin American countries, pollution of groundwater has been a serious problem for
health. We have conducted surveys in Bangladesh,
where a large-scale groundwater contamination byarsenic pauses serious threat. We have extended thissurvey to Nepal, confirming our previous findings of311

males’ susceptibility to arsenic, and demonstrated themutual relationship between malnutrition and arsenic
toxicity.
In Indonesia, we have started a study on water pollution by pesticides, metals, and others, the final goalof which is to evaluate the effects of contamination on
children’s health. A survey of water quality has been
conducted as the first step.
Air pollution in the developing countries is anothervexing environmental issue, especially in Asian urban
areas. Body burden of lead (Pb) in bus terminal workers in an Indonesian city has been examined; possible
modification of body burden by nutritional status wasshown.

References
1. Andoh, S.Y., Umezaki, M., Nakamura, K., Kizuki,
M. and Takano, T. (2006) Correlation between
indebtness, HIV/AIDS, and political status andmortalities in African countries. Public Health,120: 624-633.
2. Beekley, M.D., Abe, T., Kondo, M., Midorikawa,T. and Yamauchi, T. (2006) Comparison of
maximum aerobic capacity and body compositionof elite Sumo wrestlers to elite athletes in combat
and other sports. Journal of Sports Science &Medicine, Supple: 13-20.
3. Dewanti L, Watanabe C, Sulistiawati, Ohtsuka R.
(2006) Unexpected changes in blood pressure andhematological parameters among fasting andnonfasting workers during Ramadan in Indonesia.
European Journal of Clinical Nutrition.
4. Jiang, H.W., Umezaki, M., and Ohtsuka, R.
(2006) Inter-household variation in acceptance of
cash cropping and its effects on labor and dietary
patterns:a study in a Li hamlet in Hainan Island,
China. Anthropological Science,114(2): 165-173.
5. Maharjan M, Shrestha RR, Ahmad SA, Watanabe
C, Ohtsuka R. (2006) Prevalence of arsenicosis interai, Nepal. J Health Popul Nutr. 24:246-52.
6. Mori, K., Yoshida, K., Hoshikawa, S., Ito, S.,
Yoshida, M., Satoh, M., Watanabe, C. (2006)
Effects of perinatal exposure to low doses of
cadmium or methylmercury on thyroid hormone
metabolism in metallothionein-deficient mouseneonates. Toxicology, 228: 77-84.

7. Mori, K., Yoshida, K., Tani, J.I., Hoshikawa, S.,
Ito, S., Watanabe, C. (2006) Methylmercury
inhibits type II 5'-deiodinase activity in NB41A3
neuroblastoma cells. Toxicology Letters, 161: 96101.
8. Ohashi, J., Naka, I., Kimura, R., Tokunaga, K.,
Yamauchi, T., Natsuhara, K., Furusawa, T.,
Yamamoto, R., Nakazawa, M., Ishida, T., Ohtsuka,
R. (2006) Polymorphisms in the ABO blood groupgene in three populations in New Georgia Islands,
Solomon Islands. Journal of Human Genetics, 51(5): 407-411.
9. Sudo, N., Sekiyama, M., Maharjan, M. and
Ohtsuka, R. (2006) Gender differences in dietaryintake among adults of Hindu communities inlowland Nepal: assessment of portion sizes andfood consumption frequencies. European Journalof Clinical Nutrition, 60: 469-477.
10. Takeuchi, S., Li, Y., He, Y., Zhou, H., Moji, K.,
Ohtsuka, R. and Watanabe, C. (2006) Behaviors
associated with water contact and Schistosoma
japonicum infection in a rural village, theDongting Lake region, China. Tropical Medicine
and Health, 34(3):117-123.
11. Walker, R., Hill, K., Gurven, M., Migliano, A.,
Chagnon, N., Djurovic, G., Hames, R., Hurtado,
A.M., Oliver, W.J., De, Souza, R., Valeggia, C.,
Yamauchi, T, (2006) Growth rates, developmental
markers, and life histories in 21 small-scalesocieties. American Journal of Human Biology,
18: 295-311.
12. Yoshida M, Watanabe C, Kishimoto M, Yasutake
A, Satoh M, Sawada M, Akama Y (2006)
Behavioral changes in metallothionein-null mice
after the cessation of long-term, low-level
exposure to mercury vapor. TOXICOLOGYLETTERS 161 (3): 210-218.
13. Zhou, H., Yamauchi, T., Natsuhara, K., Yan, Z.,
Lin, H., Ichimaru, N., Kim, S. W., Ishii, M. and
Ohtsuka, R. (2006) Overweight in urban
schoolchildren assessed by body mass index andbody fat mass in Dalian, China. Journal of
Physiological Anthropology, 25: 41-48.

312

Department of
Biomedical Chemistry
Professor
Kiyoshi Kita, Ph.D.

Associate Professor
Yoh-ichi Watanabe, Ph.D.

Associate
Kimitoshi Sakamoto, Ph.D.,

Homepage

Shigeo Yoshinari, Ph.D.

http://www.sih.m.u-tokyo.ac.jp/departments-J.html#Anchor-33869

Introduction and Organization
Aim of our department is to contribute to global
health and welfare from basic research. Our department, formerly named Biochemistry and Nutrition
was renamed on April 1st, 1996 to The Department of
Biomedical Chemistry as newly affiliating with Biomedical Science Division of International Health,Graduate School of Medicine, The University of Tokyo. Prof. Kita has moved from The Institute ofMedical Science, The University of Tokyo on March
1st, 1998.

Teaching activities
Teaching activity in our department cover a broad
spectrum of biochemistry-oriented life sciences frompremise to frontiers and in either conceptual or experimental point of view
Graduate Course: Biochemistry and Nutrition I, IIThis course is comprised of lectures and seminars toprovide basic concepts and newer vistas for understanding nutrition with special reference to biochemistry and molecular biology. These include the structure and function of biomolecules, metabolism, its
regulation, and underlying mechanism at either molecular, cellular and systemic level.

Undergraduate Course: Biochemistry, Molecular Biology, Laboratory Method in Health Science, Physiological Chemistry, Nutrition, Medical Chemistry,
Practice on Medical Chemistry, Parasitology.

Research activities
Energy metabolism is essential for the survival,continued growth and reproduction of living organisms. From the standpoint of biological adaptation, we
have been studying on the molecular mechanism ofenergy transducing systems such as mitochondrial andbacterial respiratory chain. In addition, we are interested in the basic biological reactions such as protein
synthesis. Our research have been focusing on
I. Human mitochondria
1) succinate-ubiquinone reductase
2) mitochondrial myopathy
II. Ascaris suum and Caenorhabditis elegans
1) molecular mechanism of adaptation to low
oxygen tension (regulation of gene expressionof mitochondrial proteins)2) mitochondrial fumarate reductase (structure
function relationship, enzyme evolution)3) C. elegans as a model system of parasitic ne-313

matode (expression of foreign genes or cDNAs,
gene knockout)
III. Parasitic protozoa (Plasmodium falciparum , Trypanosoma brucei, Trypanosoma cruzi, Cryptosporidium)1) characterization of mitochondria as a target forthe chemotherapy2) molecular biology of mitochondrial DNA3) structure based drug design (SBDD)
IV. Protein synthesis
1) Mitochondrial protein synthesis
2) Biogenesis of cytoplasmic ribosomes

References
(1)

(2)

(3)

(4)

(5)

(6)

Genetic diversity and kinetic properties of
Trypanosoma
cruzi
dihydroorotate
dehydrogenase. Sariego, I., Annoura, T., Nara, T.,
Hashimoto, M., Tsubouchi, A., Iizumi, K.,
Makiuchi, T., Murata, E., Kita, K. and Aoki, T.
(2006) Parasitol. Int. 55, 11-16
Chemotherapeutic efficacy of ascofuranone in
Trypanosoma vivax-infected mice without
glycerol. Yabu, Y., Suzuki, T., Nihei, C.,
Minagawa, N., Hosokawa, T., Nagai, K., Kita, K.
and Ohta, N. (2006) Parasitol. Int. 55, 39-43
Kinetics and strain variation of phagosome
proteins of Entamoeba histolytica by proteomic
analysis. Okada, M., Hustond, C. D., Ouea, M.,
Manne, Petri, W.J. Jr. Kita, K. and Nozaki, T.
(2006) Mol. Biochem. Parasitol. 145, 171-183
Identification and characterization of amino acidresidues essential for the active site of
UDP-N-acetylenolpyruvylglucosamine
reductase (MurB) from Staphylococcus aureus.
Nishida, S., Kurokawa, K., Matsuo, M.,
Sakamoto, K., Ueno, K., Kita, K. and Sekimizu,
K. (2006) J. Biol. Chem. 281, 1714-1724
Up-regulation of Heme Biosynthesis during
Neuronal Differentiation. Shinjyo, N. and Kita,
K. (2006) J. Biochem. 139, 373-381
Intraerythrocytic Plasmodium falciparum utilizea broad range of serum-derived fatty acids withlimited modification for their growth. Mi-ichi, F.,
Kita, K. and Mitamura, T. (2006) Parasitology,

133, 399-410(7) Overexpression of Peroxisome ProliferatorActivated Receptor γ Coactivator -1α (PGC-1α)
Develops Muscle Atrophy with Depletion of ATP.
Miura, S., Tomitsuka, E., Kamei,Y., Yamazaki, T.,
Kai, Y.,Tamura, M., Kita, K., Nishino, I., andEzaki, O. Am. J. Physiol. (2006) 169, 1129-1139(8) An evolutionary "intermediate state" ofmitochondrial translation systems found in
Trichinella species of parasitic nematodes:
Co-evolution of tRNA and EF-Tu. Arita, M.,
Suematsu, T., Osanai, A., Inaba, T., Kamiya, H.,
aruo; Kita, K., Sisido, M., Watanabe, Y., andOhtsuki, T. (2006) Nuc. Acid. Res. 34,
5291-5299(9) Verticipyrone, a new NADH-fumarate reductase
inhibitor, produced by Verticillium sp. FKI-1083.
Ui, H., Shiomi, K., Suzuki, H., Hatano, H.,
Morimoto, H., Yamaguchi, Y., Masuma, R.,
Sunazuka, T., Shimamura, H., Sakamoto, K.,
Kita, K., Miyoshi, H., Tomoda, H. , and Omura,
S. J. Antibiot. (2006) 59, 785-790(10) Cloning and characterization of ferredoxin andferredoxin-NADP+ reductase from humanmalaria parasite. Kimata-Ariga, Y., Kurisu, G.,
Kusunoki, M., Aoki, S., Sato, D., Kobayashi T.,
Kita, K., Horii, T., and Hase, T. J. Biochem.
(2006) 141, 421-428(11) Identification of the residues involved in theunique serine specificity of Caenorhabditis
elegans mitochondrial EF- Tu2. Sato A,
Watanabe Y, Suzuki T, Komiyama M, Watanabe
K, Ohtsuki T. (2006) Biochemistry 45, 1092010927(12) A protein extension to shorten RNA: elongatedelongation factor-Tu recognizes the D-arm ofT-armless tRNAs in nematode mitochondria
Sakurai M, Watanabe Y, Watanabe K, Ohtsuki T.
(2006) Biochemical Journal 399, 249-256(13) Genomic analysis of the uncultivated marine
crenarchaeon, Cenarchaeum symbiosum Hallam
SJ, Konstantinidis KT, Brochier C, Putnam N,
Schleper C, Watanabe Y, Sugahara J, Preston C,
de la Torre, J, Richardson, PM, DeLong, EF(2006) Proc. Natl. Acad. Sci. USA, 103, 1829618301(14) Mitochondria and apicoplast of Plasmodium

314

falciparum:
behaviouronsubcellular
fractionation and the implication. Kobayashi T.,
Sato, S., Takamiya, S., Komaki-Yasuda, K., Yano,
K., Hirata, A., Onitsuka, I., Hata, M., Mi-ichi, F.,
Tanaka, T., Hase, T., Miyajima, A., Kawazu, S.,
Watanabe, Y., Kita, K. Mitochondrion (2007) 7,
125-132(15) Mitochondria and apicoplast of Plasmodium
falciparum:
behaviouronsubcellular
fractionation and the implication. Kobayashi T.,
Sato, S., Takamiya, S., Komaki-Yasuda, K., Yano,
K., Hirata, A., Onitsuka, I., Hata, M., Mi-ichi, F.,
Tanaka, T., Hase, T., Miyajima, A., Kawazu, S.,
Watanabe, Y., Kita, K. Mitochondrion (2007) 7,
125-132(16) Independent evolution of pyrimethamine
resistance in Plasmodium falciparum in
Melanesia. Mita,T., Tanabe, K., Takahashi, N.,
Tsukahara, T., Eto, H., Dysoley, L., Ohmae, H.,
Kita, K., Krudsood, S., Looareesuwan, S.,
Kaneko, A., Bjokman, A., and Kobayakawa, T.
Antimicrob. Agents. Chemother. (2007) 51,
1071-1077(17) Parasitology in Japan: Advances in drug
discovery and biochemical studies. Kita, K.,
Shiomi K., and Õmura, S. Trends in Parasitol.
(2007) 23, 223-229

316

General Surgery
Professor
Masatoshi Makuuchi, MD

Homepage
Organization
The Department of General Surgery started as an
outpatient primary care unit in 1994. The Department
serves as a screening centers for the patients with surgical problems first seen. Once diagnosis is made, thepatients are referred to appropriate specialists. Our
department consists of one professor and many otherstaffs nominated by sub-speciality departments ofSurgery. Most of them rotate between General Surgery
and sub-speciality with the duty of General Surgery
for 2-3 months a year.

Activities
Three booths in outpatient clinic are allocated to
our Department every week day. New patients without
appointments or referral letters first visit our Department. Acute surgical diseases are initially treated atour Department or referred to specialist if needed.
Most of the patients with diseases that needs operation
will be referred to specialists after appropriatedscreening. We see 20-30 such patients every day andthe total number of outpatients per year is appropriately 5000. At present, our department is not provided
with ward. The patients who need hospitalization arereferred to relevant subspeciality.

318

Department of Clinical Laboratory
Professor
Yutaka Yatomi, M.D.

Associate Professor
Hitoshi Ikeda, M.D.

Lecturer
Katsu Takenaka, M.D.,

Tatsuo Shimosawa, M.D.

Daiya Takai, M.D.,

Masato Yumoto, M.D.

Associate
Yukako Koike, M.D.,

Aya Ebihara, M.D.,

Makoto Kaneko, M.D.

Chief Technologist
Hiromitsu Yokota, Ph.D.

Homepage

http://www.h.u-tokyo.ac.jp/patient/depts/kensa.html

Introduction and Organization
Clinical Laboratory Center consists of 11 doctors, achief technologist, 63 technicians, and 2 nurses, and isdivided into the following sections. The second - generation Laboratory Automation System is in full operation, and ordering of laboratory tests, the flow ofsamples, operation of laboratory analyzers, quality
control of analysis, and data reporting are all controlled by the Laboratory Automation computer system. This system has greatly improved the quality,
safety, and efficiency of the laboratory and contributed
to both patients and doctors by providing rapid andhigh-quality laboratory testing.
The 1st Section
This section deals mainly with the maintenance oflaboratory system, blood and urine sampling, and urinalysis. In 2005, 199,262 outpatient blood sampling
were performed in this section.
The 2nd Section
This section deals with clinical biochemistry andimmuno-serology tests. In 2005, over 3,671,969 serum

enzyme tests (such as AST and ALT), and 411,111
immunological tests were performed.
The 3rd Section
This section deals with hematology and DM-related
tests, gene analysis tests and urinalysis. In 2005,
835,722 samples were examined for complete blood
cell counts, cell surface marker analysis, prothrombin
time, fibrinogen, glucose, and HbAIC tests, and167,037 urine samples were examined.
The 4th Section
This section deals with physiological tests, including circulatory, pulmonary, and neuromuscular function ones. In 2005, 30,495 ECG, 18,096 pulmonary
function tests, 16,523 echocardiography tests, 9,682
abdominal echography tests, and 8,305 EEG were
performed.
The Hospital Ward Section
This section has been recently founded and is incharge of laboratory tests, mainly ECG, for seriously-ill, hospitalized patients. In the future, this section is going to be further expanded since there is so319

much demand from clinical doctors.

Teaching activities
Lectures are given to the fourth and fifth grade
medical students on clinical tests including hematology, chemistry, endocrinology, immunology, bacteriology, cardiology, and pulmonary function. The reversed CPC program is presented to the sixth gradestudents. Laboratory practice teaching is provided forthe fifth year medical students, in small groups of 6-7
students for one-week duration. In this course, students learn clinical and practical knowledge and techniques on various laboratory tests. Students from professional schools also study laboratory medicine under
the guidance of members in Clinical Laboratory Center.

Research activities
The main goal of our research projects is the development of new and useful laboratory tests, andelucidation of pathophysiology of diseases throughlaboratory tests. The areas included are: i) hematological analysis, ii) cell surface analysis using flow
cytometry, iii) analysis of life-style involvement inclinical laboratory data, iv) bioactive lipids, v) hormones, including FGF-23 and adrenomedullin, vi)
analysis of cardiac functions using ultrasound, vii)
hepatic fibrosis, viii) ischemic reperfusion injury of
the liver, ix) analysis of brain function using magnetoencephalography and near-infrared spectroscopy,
and x) the improvement of the current laboratory test
methods is constantly performed in all laboratory sections.

References
1. Ikeda, H., Nagashima, K., Yanase, M., Tomiya, T.,
Arai, M., Inoue, Y., Tejima, K., Nishikawa, T.,
Watanabe, N., Kitamura, K., Isono, T., Yahagi, N.,
Noiri, E., Inao, M., Mochida, S., Kume, Y., Yatomi, Y., Nakahara, K., Omata, M., and Fujiwara,
K. The herbal medicine inchin-ko-to (TJ-135) induces apoptosis in cultured rat hepatic stellate
cells. Life Sci. 78: 2226-2233, 2006.
2. Karino, S., Yumoto, M., Itoh, K., Uno, A., Ya-

makawa, K., Sekimoto, S., and Kaga, K. Neuromagnetic responses to binaural beat in humancerebral cortex. J. Neurophysiol. 96: 1927-1938,
2006.
3. Kudo, N., Kasai, K., Itoh, K., Koshida, I., Yumoto,M., Kato, M., Kamio, S., Araki, T., Nakagome, K.,
Fukuda, M., Yamasue, H., Yamada, H., Abe, O.,
Kato, N., and Iwanami, A. Comparison between
mismatch negativity amplitude and magnetic
mismatch field strength in normal adults. Biol.
Psychol. 71: 54-62, 2006.
4. Matsui, H., Shimosawa, T., Uetake, Y., Wang, H.,
Ogura, S., Kaneko, T., Liu, J., Ando, K., and Fujita, T. Protective effect of potassium against thehypertensive cardiac dysfunction: association withreactive oxygen species reduction. Hypertension
48: 225-231, 2006.
5. Moriya, J., Takimoto, Y., Yoshiuchi, K., Shimosawa, T., and Akabayashi, A. Plasma agoutirelated protein levels in women with anorexia
nervosa. Psychoneuroendocrinology 31: 10571061, 2006.
6. Ogata, E., Yumoto, M., Itoh, K., Sekimoto, S.,
Karino, S., and Kaga, K. A magnetoencephalographic study of Japanese vowel processing.
Neuroreport 17: 1127-1131, 2006.
7. Ohkawa, R., Hisano, N., Nakamura, K., Okubo, S.,
Yokota, H., and Yatomi, Y. Lysophospholipase D
activity exists in the urine to catalyse the formation of lysophosphatidic acid. Nephrol. Dial.
Transplant. 21: 3612-3613, 2006.
8. Ohmori, T., Yatomi, Y., Nonaka, T., Kobayashi, Y.,
Madoiwa, S., Mimuro, J., Ozaki, Y., and Sakata, Y.
Aspirin resistance detected with aggregometry
cannot be explained by cyclooxygenase activity:
involvement of other signaling pathway(s) in cardiovascular events of aspirin-treated patients. J.
Thromb. Haemost. 4: 1271-1278, 2006.
9. Sakamoto, A., Okamoto, K., Ishizaka, N., Tejima,K., Hirata, Y., and Nagai, R. (18) Ffluorodeoxyglucose positron emission tomography in a case of retroperitoneal fibrosis. Int. HeartJ. 47: 645-650, 2006.
10. Saito, A., Motomura, N., Kakimi, K., Ono, M.,
Takai, D., Sumida, S., and Takamoto, S. Cryopreservation does not alter the allogenicity and development of vasculopathy in post-transplant rat

320

aortas. Cryobiology 52: 251-260, 2006.
11. Satoh, K., Yatomi, Y., and Ozaki, Y. A new method for assessment of an anti-5HT(2A) agent,sarpogrelate hydrochloride, on platelet aggregation. J. Thromb. Haemost. 4: 479-481, 2006.
12. Tanaka, M., Okudaira, S., Kishi, Y., Ohkawa, R.,
Iseki, S., Ota, M., Noji, S., Yatomi, Y., Aoki, J.,
and Arai, H. Autotaxin stabilizes blood vessels
and is required for embryonic vasculature by
producing lysophosphatidic acid. J. Biol. Chem.
281: 25822-25830, 2006.
13. Yamashita, H., Kitayama, J., Kanno, N., Yatomi,
Y., and Nagawa, H. Hyperfibrinogenemia is associated with lymphatic as well as hematogenous
metastasis and worse clinical outcome in T2 gastric cancer. BMC Cancer 6: 147, 2006.
14. Yamashita, H., Kitayama, J., Shida, D., Yamaguchi, H., Mori, K., Osada, M., Aoki, S., Yatomi, Y.,
Takuwa, Y., and Nagawa, H. Sphingosine
1-phosphate receptor expression profile in humangastric cancer cells: differential regulation on the
migration and proliferation. J. Surg. Res. 130: 8087, 2006.
15. Yatomi, Y. Sphingosine 1-phosphate in vascularbiology: possible therapeutic strategies to control
vascular diseases. Curr. Pharm. Des. 12: 575-587,
2006.
16. Yatomi, Y., Aoki, S., and Igarashi, Y. Sphingosine
1-phosphate-related metabolism in the blood vessel. Sphingolipid Biology (eds., Y. Hirabayashi, Y.
Igarashi, and A.H. Merrill, Jr.) pp. 427-439.
Springer-Verlag, Tokyo. 2006.

321

Surgical Center
Director (Professor)
Hiroshi Yasuhara M.D., Ph.D.

Associate Professor
Yoshikazu Mimura, M.D., Ph.D.
Yushi Uetera, M.D., Ph.D.

Lecturer
Nobusuke Ohara, M.D., Ph.D.
Ryoji Fukushima, M.D., Ph.D.
Takami Komatsu, M.D., Ph.D.

Associate
Toshihiko Obayashi, M.D., Ph.D.
Saito Yuhei, Ph.D.

Homepage
Introduction and Organization
Operating rooms were centralized for the first timein Japan in the University of Tokyo Hospital on July
1955. Surgical center was located in the surgical ward
building till December 1987. The center moved to the
new central building on January 1988. The surgicalcenter had 14 operating rooms, one of which was a
bio-clean room. The administration staffs consisted of
5 doctors, 54 nurses, 6 technical officials, 6 part-time
employees. The surgical center became to afford services to 18 clinical departments after the new surgicalcenter started.
The total number of operations did not apparently
increase between 1999 and 2000, partly because of theshortage in the number of operating rooms and nursing staffs.
In July 2001, the branch hospital, which was located in Mejiro, joined to the University of Tokyo
Hospital in Hongo and a new ward building opened in
October 2001. Then, the number of operations remarkably increased and became over 7500. Anothermanagement effort was made to enforce the availability of the operating rooms. Two new operating rooms
were tentatively used to overcome the tremendous
increase in the number of operations. The one is on
the ICU/CCU/HCU floor in the new ward building
and the other room was in the outpatient building,which had been used for the orthopedic patients. This
operating room was used for the short-stay and day
surgery of orthopedics as well.
Until September 2001, the elective operations had
been performed daily in 9 operating rooms on average.
However, the elective operations began to be done in
12 operating rooms after October 2001. The numberof operations annually increased afterwards. Over7,500 operations including 1096 emergency cases
were done in 2004.
Another new central building, which had additional
11 operating rooms, is now open from the beginningof the year 2007 to resolve the chronic shortage of theavailability of operating rooms. As a result, the total
number of operating rooms became 23, and then thenumber of operations has been dramatically increased.

322

In the year 2006, 8,322 operations were performed inour surgical center including over 1000 emergency
operations, which is 1.5 times comparing to those in2001.
Our major concern has been an apparent increase in
the patients with positive results of the preoperative
microbiological test such as such as tuberculosis,
MRSA, pseudomonas aeruginosa, HBV, HCV andHIV. Those patients have been increasing by 5-18%
per year over the last 4 years. More and more administrative efforts might be needed to protect the staffs
as well as the patients as the new infectious agent suchas prion may be found in the near future.

Activities of Surgical Center
Our work covers from the management of operation
schedule to the teaching and research.

Management of Surgical CenterAll operations of in-patients are performed in 23
operating rooms of the surgical center. Computer system has been introduced in order to deal with the information on the operation. In May 1999, on-line
computer system was introduced for ordering systemof the elective and emergency operations. Then, all theoperations have been ordered through the computer
terminal set up at each clinical department since May
l999. The doctors and nurses became to be able tomanage postoperative information as well through thecomputer system since March 2000.
For the efficient management of operation, the information on the status of the operations has been displayed on the computer monitor screen since May
1997. This monitor screen also gives the every hospital staff the information whether there are any operating rooms available on the next day. Furthermore,since November 2000, the hospital staffs became to beable to see how each clinical department plans to use
the operating rooms on the next week through thehospital computer network.
Digitalized visual information such as photographsof operative fields and resected organs has been distributed to each clinical department through hospitalcomputer network since February 1997. Moreover,real-time monitoring visual information of the opera-

tive fields has been distributed to each clinical department through the hospital computer network sinceJune 1999.
In the new ward building SPD and progressive patient care system started for the management of our
hospital in October 2001. Then, the SPD system wasintroduced for the surgical center in September 2002.
The complicated surgical procedures including organ transplantation microvascular surgery, cardiovascular surgery, minimally invasive surgery and orthopedic surgery have recently increased dramatically. In
addition, more and more patients recently underwent
surgery using artificial implants such as vascular
prosthesis, joint prosthesis and intraocular lenses.
The advanced techniques have been employed in
the operating rooms. Those include navigation surgery
in neurosurgical, orthopedic and ENT (ear, nose andthroat) operations, and arterial stent for the thoracic
aortic aneurysms. The minimally invasive surgery
such as MIDCAB operations is also performed in the
CABG as well as a in the treatment of heart anomalies
such as ASD and VSD. In addition, organ transplantation and intraoperative three-dimensional echo-guided
surgery are performed in the surgical center.
Another recent trend is the presence of emergenceand re-emergence infectious diseases such as HIV andtuberculosis among the operated patients. Therefore, it
is mandatory to educate how to prevent nosocomial
and occupational infections in the surgical center. For
instance, the principles of standard precautions andtransmission-based precautions should be taught to all
health care staffs in the surgical center.
The number of immune-compromised hosts andcomplex surgical procedures will continue to increase
throughout the 21 century. Therefore, the surgicalcenter ought to be playing an important role because
the improvement of the management skill is mandatory to meet the increase in the perioperative healthcare services for those patients.

Teaching Activities
The following lectures are given to the undergraduates and postgraduates: aseptic techniques, sterilization methods, disinfection methods, prevention of perioperative infections, humoral and cellular responses
to trauma and shock, training of scrubbing and gown

323

techniques, Curriculum is updated every year. For
example, introductory course for disinfection, sterilization and preservation of surgical instruments andmedical devices was added in the training courses in
1998, which gained interest and popularity among
students.
In the surgical center, the innovative surgical instruments and medical devices are recently introduced
to perform highly advanced operations such as in thenavigation surgery, transplantation surgery, cardiovascular surgery and so forth. Consequently, education
has become one of the most important activities in thesurgical center. The lectures of advanced technologies
are in the curriculum for the surgeons, nursing staffs
and medical electronics engineers so that they canunderstand how to use them properly.
Lectures for the nursing staffs consist of a freshmancourse and an advanced course. The freshman course
is a basic training course as a scrub nurse and a circulating nurse. It consists of lectures of aseptic techniques, de-contamination methods, sterilization methods, prevention of perioperative infections, andtraining of scrubbing and gown techniques as wall as
aseptic preparation of surgical instruments in the operating room. An advanced course is also prepared tothe experienced nurses. The purpose of this course is
to upgrade their perioperative nursing skills so thatthey can afford full nursing skills in the complex surgical procedures such as transplantation surgery,open-heart surgery and neurosurgery.
There is also a training course to medical electronics engineers and students of medical electronics. This
training course consists of introduction on the medical
electronic instruments and devices, precautions ofaccidental troubles in handling surgical instruments
and medical devices, development of new surgicalinstruments and medical devices, cardiopulmonary
bypass techniques and illumination techniques in theoperating fields. The contents of this course are summarized in the manual for the nursing staffs and contribute to decrease the number of accidents in handling surgical instruments and medical devices.
The on-job training are given to the non-nursing
staffs such as technical officials and temporary employees and performed when they start their careers inthe surgical center. They are lectured on aseptic techniques, sterilization methods, disinfection methods,

prevention of perioperative infections and how tocheck the faults in the reusable surgical instruments
such as forceps, scissors and clamps. These contents
are summarized in the manual. Lectures are also given
to senior technical officers and temporary employees
to upgrade their technical knowledge and skills.

Research Activitiesl ) Introduction of aseptic environment in the operating theaters
2) Development of new sterilization methods
3) International standardization of sterilization methods
4) Perioperative infection control of patients undergoing operations and prevention of occupational
infection of medical staffs working in the surgicalcenter5) Improvement of cost-effectiveness in the management of surgical center
6) Precautions of accidental troubles in the handlingsurgical instruments and medical devises7) Improvement of cost-effectiveness in sterilizationand preservation of medical instruments
8) Cost-effectiveness analysis of disposable and reusable surgical instruments
9) Development of new surgical instruments andmedical devisesl0) Computer aided surgery11) Intra-operative radiation therapy12) Surgical treatment on the basis of molecular biology13) Inter-hospital visual communications via satellite
system14) International comparison of effectiveness in the
management of surgical center15) Computer aided anesthesia
16) Three dimensional processing of visual information17) Improvement of minimally invasive surgery andmicrosurgery

References（2005-2006）
1. Hayashida M, Kin N, Tomioka T, Orii R, Sekiyama H, Usui H, Chinzei M, Hanaoka K: Cerebral
ischaemia during cardiac surgery in children de-

324

2.

3.

4.

5.

6.

tected by combined monitoring of BIS andnear-infrared spectroscopy. Br J Anaesth 92:
662-9, 2005
Hatao F, Hiki N, Mimura Y, Ogawa T, Kojima J,
Mafune K, Hawkins LD, Muroi M, Tanamoto K,
Kaminishi M: The induction of super-resistanceusing synthetic lipopolysaccharide receptor agonist rescues fatal endotoxemia in rats without excessive immunosuppression. Shock 23: 365-370,
2005
Uetera Y, et al. A simple method to perform vacuum leak test in the prevacuum autoclave without
the automatic test mode. PDA Journal of GMP
and Validation in Japan 7, pp146-149, 2005
Yasuhara H. Acute mesenteric ischemia: The
challenge of gastroenterology. Surgery today
35:185-95, 2005
Yasuhara H, Niwa H, Takenoue T, Naka S. Factors
influencing mortality of acute intestinal infarction
associated with SIRS. Hepatogastroenterology
52:1474-8, 2005
Furuya Y, Yasuhara H, Yanagie H, Naka S, Takenoue T, Shinkawa H, Niwa H, Kikuchi T, Nagao. Role of Ganglion Cells in Sigmoid Volvulus.
World J Surg 29:88-91, 2005

325

Department of Clinical Radiology
Professor (department manager)
Kuni Ohtomo, M.D.,Ph.D.

Lecturer (vice manager)
Tomohiko Masumoto, M.D.,Ph.D.

Associate
Shinichi Inoh, M.D.

Homepage

http://www.ut-radiology.umin.jp/

Introduction and Organization
In the Department of Clinical Radiology, clinicalservices on Diagnostic Radiology (imaging and intervention), Radiation Oncology (radiotherapy), Nuclear
Medicine and the Radiation Safety Control System areprovided in cooperation with radiology technologists
and nurses. Present constituent members are as follows: three medical doctors, 52 radiological technicians, 2 assistants, 18 nurses, and 1 technical officialof the radiation control. The staff members of the Department of Radiology (teachers, the graduate school
students, medical staffs, and the clinical trainees) join
this. In addition, the doctors and the nurses of otherclinical departments cooperate and are also engaged in
the clinical radiology activities. The educational
training and registration of the radiation engaging
persons are controlled according to the University ofTokyo Hospital Ionizing Radiation Injury Prevention
Rules.
Department of Clinical Radiology covers four major fields: (1) Diagnostic Radiology, (2) Radiation
Oncology, (3) Nuclear Medicine and (4) the Radiation
Safety Control System. The Diagnostic Radiology
Section is mainly operated at the first floor in theCentral Clinic Building 1. Parts of the diagnostic activities are done at the Central Clinic Building 2 (theMR rooms, the operation rooms, and the emergency
department) and some other clinical departments. The

services provided are X-ray imaging, fluoroscopic
imaging, computed tomography (CT), magnetic resonance imaging (MRI) and angiography. Radiation
Oncology Section is operated at third basement floorof the Central Clinic Building 2. The outpatient clinic
is also located here and not in the Outpatient Clinic
building. The methods of therapy provided are linear
accelerator (LINAC), gamma-knife, Remote After
Loading System (RALS) and Brachytherapy (Radioactive Seed Implantation Therapy). Nuclear Medicine
Section is operated at the basement floor of the Central Clinic Building 1. The methods of examination
provided are conventional scintigram, SPECT and
PET. The office of Radiation Safety Control System islocated at the third floor of the old Central Clinic
Building.
Department of Clinical Radiology is actively participating in the following projects. 1) PACS: We haverecently developed a radiology information system(RIS) networking with hospital information system(HIS) and PACS (picture archiving and communicating system). The PACS of the whole hospital (thefilm-less imaging system) was established in 2003.
The new reporting system was installed in 2002. 2)
Radiation Safety Control: Stimulated by the need forevaluating the individual accumulated exposure doseby medical radiation, we have started a working group
to solve this problem. We aim to provide the accumulated exposure dose data on RIS. 3) Image Computing& Analysis Laboratory: The clinical section of this326

project is located at the reading room in the Diagnostic Radiology Section. The main services are processing of volume image data into clinical 3D-images andanalysis of imaging data. 4) Researches on new radiology techniques: Ongoing collaborative researches
are as follows: image-guided radiation therapy, clinical PET, multi-detector row CT, 3-Tesla MRI, flat
panel detector.

tileaf collimator systems, which is utilized mainly for
non-coplanar radiation therapy in many patients especially with brain tumor or head and neck tumor. The
rate of the non-coplanar radiation therapy is over 25%
and surpasses those of other institutions. Recently, a
new linear accelerator system with cone-beam CT
technology was introduced to our hospital, which enabled image-guided radiation therapy.

Clinical activities

3) Nuclear medicine:
Positron Emission Tomography (PET) and Single
Photon Emission Computed Tomography (SPECT) are
the main activities in the clinical and research work.
These nuclear imaging procedures are chiefly performed and reported by radiologists and cardiologists.
Cerebral blood flow, glucose metabolism and neuralsynaptic functions are measured for the understandingof normal and pathophysiological states of CNS disorders, using a variety of positron-emitter radiotracer,such as [O-15] H2O, CO2, O2, CO, [F-18] FDG, [C-11]
methionine, [F-18] Dopa, [C-11] NMSP, NMPB and[C-11] raclopride. The study of dementia using
SPECT and the standard brain atlas has made it possible to categorize the type of dementia. Evaluation of
dopaminergic function by PET is very important in the
differential diagnosis of Parkinsonism. Cardiac PET
and SPECT are also active fields. Myocardial viability,
vascular reserve and sympathetic nerve denervation in
the ischemic heart disease are evaluated with [F-18]
FDG, [N-13] NH3, Tl-201 and [I-123] MIBG. Higher
brain functions such as reading, speech and thinking
have been studied with PET by comparing blood flow
and receptor binding potential (BP) under various
tasks and at rest. For the precise localization of activated brain function, computer processing and reconstruction of composite images of function and anatomy is an essential subject for investigation. Wholebody FDG-PET is one of the most promising studies
for exploring metastatic lesions of cancer patients.
Combination display of SPECT/PET with XCT/MRI
would be a routine job and anatomo-functional images
would play an important role in the clinical management of the patients.

1) Diagnostic Radiology:
The section of diagnostic radiology is responsible
for all the clinical examinations of CT, MRI, and angiography and vascular interventional procedures except for cardiac and peripheral arterial studies. All ofthese examinations are performed under the requests
of clinicians. Over one hundred and fifty CT examinations are performed using five MDCT scanners eachday. Interventional procedure such as percutaneous
biopsy and abscess drainage are also done by CT
guidance. About fifty MR examinations are done using 1.5-Tesla and 3-Tesla scanners every day. About
six angiographies, most of which are interventional
procedures including arterial embolization, arterial
infusion therapy, arterial infusion port placement, andangioplasty, are done by the radiologists using two
angiographic units.
In clinical research works, efficacy of MDCT has
been investigated in all parts from the head to extremities. New three-dimensional approaches havebeen also developed. Clinical research and basic animal experiments are in progress in the field of functional MR imaging and diffusion and perfusion MR
techniques.
2) Radiation Oncology:
The radiation therapy is performed with two linear
accelerators, an intracavitary irradiation device(RALS), and a gamma knife for radiosurgery. The
network system connecting these radiotherapy equipments, CT/MR devices, and treatment planning systems was already constructed. Each year, over 700
new patients receive radiation therapy in the Radiation
Oncology section. Highly accurate 3D radiation therapy is the most outstanding feature. We have developed a new linear accelerator with C-arm and mul-

In conclusion, the department of clinical radiology
is a service section to all clinical departments. Main
supporter as the doctor is a radiologist. However, the327

cooperation with the radiation diagnosis and treatment
engaging persons of other clinical departments, technicians and nurses must be reinforced. We want tomake still more effort to achieve the cooperation andimprove clinical activities in the department of clinical radiology.

References
See the corresponding part of the department ofRadiology.

328

Delivery Unit
Professor
Takashi Igarashi

Lecturer
Yoshimasa Kamei

Homepage

http://www.iiosan.umin.jp/index.html

Organization
The Delivery Unit of the University of Tokyo Hospital is organized by one professor, one associate, and5-10 fellows. All the staff members are taking part inresearch activities of reproductive endocrinology, gynecologic oncology, or perinatal medicine, as well as
being engaged with in-patient and out-patient care forpregnant women including the activities in the delivery units.

Activities
Total number of delivery cases from April 2006 to
March 2007 is 774, whereas that from April 2005 to
March 2006 is 557.
Recently cases of obstetrical emergencies like abruptio placentae, eclampsia and uterine rupturestransported from neighboring hospitals have been increasing. These patients are treated by two or three
doctors and three midwives in charge under roundthe-clock system. Our service is an important part ofTokyo Metropolitan Service System for Maternal
Welfare and Perinatal Medicine.

References from April 2005 to
March 2007
[See Department of Perinatal Medicine.]

329

Central Rehabilitation Service
Professor
Nobuhiko Haga, M.D.

Associate
Naoyuki Miyake, M.D.,

Shun-ichi Furukawa, M.D.

Takashi Maeno, M.D.

Homepage

http://www.h.u-tokyo.ac.jp/patient/depts.html

Introduction and Organization
The physical therapy service started in 1963 at the
University of Tokyo Hospital, and then expanded toinclude occupational therapy and social work section.
In 1966 this service was converted to the central rehabilitation service department as a part of the Central
Diagnostic and Therapeutic Service Department. The
Central Rehabilitation Service became an independent
unit in 1970. After the reorganization of the Universityof Tokyo Hospital according to major organic classification in 1998, outpatient clinic as rehabilitation
medicine was installed. The formal title of our unit
was changed from the Physical Therapy Department
to the Rehabilitation Department by the budget measures in the fiscal year 2001, and we integrated the related personnel categories, which belonged to the orthopedic surgery department and the physical medicine department.
At the present time our department consists of four
sections. Rehabilitation physicians’ section includes
three full-time doctors and two other part-time doctors.
They work chiefly for clinical practice in medical rehabilitation service, but also have to engage in teaching activities for medical students. Fourteen physicaltherapists and five acupuncture therapists are working
in the physical therapy section. In the occupational
therapy section, three occupational therapists work forthe general rehabilitation service and the other two
therapists work for the psychiatric rehabilitation. In
the Day-care Unit, a clinical psychologist and a nurse
also work. In 2006, speech therapists and orthoptists

who belong to other departments in the University ofTokyo Hospital are going to be included in our department.

Clinical activities
There is not enough doctors arranged for the department of rehabilitation medicine, and we cannot
run own beds for rehabilitation patients at present. The
professor serves as a director of Central Rehabilitation
Service Department of the University of Tokyo Hospital. Both departments are united and engage in clinical practice. We have at present no charged ward, andtreat about 1,000 new referrals annually from almost
all the departments of the university hospital. We always take charge of about 150 patients corresponding
about 15% of the whole number of inpatients. We also
see 15 people per day at the outpatient rehabilitation
setting. The numerical ratio of outpatient is being reduced in order to give priority to the clinical service
corresponding to needs expansion of service to inpatients.

Teaching activities
We have provided several clinical curriculums on
rehabilitation medicine for 4th, 5th, and 6th year
medical students since 1973. The systematic lecture
series for 4th year medical students (M2) include thesubjects on rehabilitation for disorders such as cerebrovascular disturbances, spinal cord injuries andspina bifida, neuromuscular diseases, bone and joint

330

diseases, and cerebral palsy as well as on outline ofrehabilitation, welfare system, and prostheses / orthoses . We have provided a clinical practice in small
group, so-called bedside learning for 5th year students
from Wednesday to Friday every other week. Theyexperience a few patients and learn how to take a patients’ history, physical findings, functional evaluation,and how to plan rehabilitation programs. We have introduced a few of elective students for clinical clerkship to our collaborating hospitals with specialized
rehabilitation ward.
In addition, we have provided the training of comedical students including physical therapy and occupational therapy. Twenty students or more come andstay at the university hospital annually as a long-term
clerkship from several PT/OT training schools.
Nine graduate school students entered by 2006 andthree of them acquired a degree of Ph.D. and graduated.

Research activities
Our research activities are growing up. In 2006, theCentral Rehabilitation Service Department moved to
the new building and a research laboratory was provided for the first time. As the motion analysis system
was partially renewed, we are planning our researches
mainly in the field of musculoskeletal disabilities. In
addition, we are planning collaborating researcheswith other departments in our hospital, other faculties
in our university, and institutions outside the University of Tokyo. The ongoing and scheduled projects are
as follows.
1) 3D-motion analysis of patients with joint disorders in the lower extremities
2) Estimation of supported motion by humanmachine coadaptation system
3) Analysis of hemodynamic changes in the lower
extremities with passive motion4) Estimation of standing balance and the effect bypassive stimulation
5) Analysis of motion and energy expenditure in theactivities of daily living in the physically disabled
6) Non-invasive evaluation of lower limb motor
function in spina bifida
7) Prevention of requiring long-time care withphysical exercise
8) Disabilities and handicaps in patients with skeletal dysplasias
9) Mechanism of physical therapy on the change ofpain and perceptional threshold10) Evaluation of higher brain dysfunction

References
1. Chiba Y, Yamaguchi A, Eto F. Assessment of sensory neglect: a study using moving images. Neuropsychol Rehabil. 2006;16:641-652.
2. Haga N, Masuda K, Takikawa K. Osteochondral
destruction in the hand following bee stings: acase report of an infant. Hand Surg. 2006;11(3):143-145.
3. Itoh T, Shirahata S, Nakashima E, Maeda K, Haga
N, Kitoh H, Kosaki R, Ohashi H, Nishimura G,
Ikegawa S. Comprehensive screening of multiple
epiphyseal dysplasia mutations in Japanese population. Am J Med Genet Part A. 2006;140A:
1280-1284.
4. Kanamori Y, Tomonaga T, Sugiyama M, Hashizume K, Goishi K, Haga N. Bizarre presentationof epigastric heteropagus: report of a case. Surg
Today. 2006;36:914-918.
5. Kasuya D: Acupuncture for diabetic neuropathy.
KAIM. 2006;1(2):13-20.
6. Saotome T, Sekino M, Eto F, Ueno S. Evaluationof diffusional anisotropy and microscopic structure in skeletal muscles using magnetic resonance.
Magnetic Resonance Imaging. 2006;24:19-25.
7. Takikawa K, Haga N, Maruyama T, Nakatomi A,
Kondoh T, Makita Y, Hata A, Kawabata H, Ikegawa S. Spine and rib abnormalities and stature in
spondylocostal dysostosis. Spine. 2006;31:E192197.

331

Division of Diagnostic Pathology
Professor (Director)
Masashi Fukayama, M.D., Ph.D.*

Associate Professor (Deputy Director)
Noriyoshi Fukushima, M.D., Ph.D.*

Lecturer
Hiroshi Uozaki, M.D., Ph.D.,

Satoshi Ohta, M.D., Ph.D.*

Lecturer (Hospital)
Kenji Kashima, M.D., Ph.D.,

Yutaka Takazawa, M.D., Ph.D.,

Toru Motoi, M.D., Ph.D. (visiting researcher, USA)

AssociateJunji Shibahara, M.D., Ph.D.,

Tetsuo Ushiku, M.D., Ph.D.,

Akiteru Goto, M.D., Ph.D.*,

Takashi Sakatani, M.D., Ph.D.*

Clinical Fellow
Naoko Yamauchi, M.D., Ph.D,

Homepage

Rumi Hino, M.D., Ph.D.

http://pathol.umin.ac.jp/

Introduction and Organization
Department of Pathology and Diagnostic Pathology(*) and Division of Diagnostic Pathology of University Hospital have been united to function as a unit.
This union is responsible for the pathologic practice of
the University Hospital (autopsy and surgical pathology), as well as for education and research of humanpathology.
The proper staffs were 1 lecturer, two lecturers(hospital), two associates, and two clinical staffs.
The relocation to the brand-new clinical center II
was implemented on December 2006. The new
equipments are suitable for University Hospital andfor pathological diagnosis of following generation.
Especially, the deputy director, Fukushima and thechief technician, Kaneko took the leadership for themoving.

Clinical activities (pathologic diagnosis and autopsy)
Annual statistics of the pathologic practice in 2006
are 12,527 cases of biopsy, 18,547 of cytology, 620 offrozen histology, 335 of intra-operative cytology and
84 of autopsy (20% as autopsy rate).
Clinico-pathological conferences (CPCs) for thetwo autopsy cases are held every month in the hospital.
In 2006, 126th – 136th CPC were held. Furthermore,
surgical pathological conferences are regularly heldwith each clinical division, and discusses the cases ofvarious tumors, including thorax, upper gastrointestinal tract, neurosurgery, liver, pancreat-biliary tract,urology, gynecology, mammary gland, and orthopedics, as well as biopsy cases of liver, kidney and skin.
Our aim of the pathologic practice is to provide thecorrect diagnosis as soon as possible. We are addressing ‘one-day pathology’ using a newly developed
rapid-histoprocessing machinery. Furthermore, a vir-332

tual slide scanner has been installed, which enabled us
to save the consultation specimens as digital information. We are setting out a future providing system ofpathologic images for clinical divisions. Lecturer Uozaki is mainly in charge of this project.
Being involved in “The Model Project for Inspection and Analysis of the Death Associated with Medical Practice” of Health, Labor and Welfare Ministry,
we submitted autopsy assessments concerning ninecases of “the death associated with medical practice”
in cooperation with Department of Forensic Medicine.
Hospital lecturer, Takasawa contributed a great deal
about them.

Teaching activities
The lectures and exercise course of systemic pathology are for the 2nd grade–students. Clinical clerkship and bed-side learning (BSL) course of autopsy
and surgical pathology are for the 3rd and 4th gradestudents, respectively.
The new system of internship has started since 2004,
and all interns are required to submit at least one report of CPC case. The Division of Diagnostic Pathology received five interns in 2006 for the second year
program of their internship.

Research activities
We are developing the tumor specific antibodies incollaboration with Genome Science Division, Research Center for Advanced Science and Technology,
the University of Tokyo. Based on the DNA array dataof various human neoplasms, monoclonal antibodies
against candidate gene products are generated. In addition, we are in the process of constructing the tissue
array of neoplastic and non-neoplastic tissues in orderto facilitate the screening process of immunohistochemistry,.

References
See the corresponding section of Department of
Pathology and Diagnostic Pathology

333

Department of Corneal
Transplantation
Associate Professor
Shiro Amano, M.D., Ph.D.

Homepage

http://www.h.u-tokyo.ac.jp/patient/depts/kakumaku.html

Introduction and Organization
The department of corneal transplantation was established in 1976 as one of clinical sections in the
University of Tokyo Hospital. The purpose of the establishment of this section is to carry out and promotecorneal transplantation and to perform clinical andbasic research in the corneal diseases and corneal
transplantation. The section is composed of a director(associate professor).

Clinical activities
The clinical activities of this section include corneal
transplantation and outpatient clinics for various corneal diseases as a consulting corneal service. The director is responsible not only for corneal transplantation but also for general ophthalmological practice asa senior staff member of Department of Ophthalmology, University of Tokyo. The corneal service is held
every Wednesday. At the corneal service, we determine indication for corneal transplantation and follow
up patients after the surgery. We also diagnose andtreat various corneal diseases. The corneal service isconducted by the director and doctors from related
hospitals. The patients who enrolled in the corneal
service have exceeded 5000. The total number of corneal transplantation has reached 1500 cases since westarted keratoplasties in 1971. Approximately 50 corneal transplantations have been performed annually.
The other important activities of the section include
mediation of donor eyes to other university hospitals
and medical institutes that need donor eyes for corneal
transplantation.

Followings are our main clinical themes to be pursued to improve the safety and prognosis of corneal
transplantation.
1) Thorough examination of donor eyes not only byslit-lamp biomicroscope but also by specular microscope.
2) Positive proof that donors were free of such infectious diseases as viral hepatitis, syphilis, AIDS
and acute T-cell leukemia to prevent transmission
to recipient patients through grafting.
3) Introduction of sclero-corneal preservation of donor eyes, because sclero-corneal preservation ismore suitable for longer preservation than conventional whole eye preservation.
4) The long-term natural course of keratoconus has
been investigated with corneal topography.

Teaching activities
As an undergraduate course, we give lectures on
corneal physiology, corneal diseases, and corneal
transplantation. In addition, we are engaged in practical training for medical students on ophthalmologicalexaminations at the outpatient clinic. As a postgraduate course, we give lectures on topics concerning corneal transplantation, corneal diseases and new medical
therapies.

Research activities
1. Regenerative medicine for corneal diseases.
We have pursued to apply regenerative medicine tocorneal diseases. In patients with chemical burn ofocular surface and Stevens-Johnson syndrome, we try

334

to reconstruct the ocular surface with autologous cultivated limbal, conjunctival or oral epithelial cells. We
also use cultured human corneal endothelial cells,
collagen sheet and amniotic membrane to construct
sheets with corneal endothelial cells. These sheets
have the same degree of pump function as corneal
endothelium. We have investigated the potentiality ofcollagen extracted from animal dermis for reconstruction of corneal stroma. We also examined the potential
clinical usefulness of acellularized porcine corneal
stroma.
2. Tissue stem cells in the cornea.
Using neurosphere method, we successfully isolated
tissue stem cells in the corneal epithelium, stroma andendothelium. Each tissue stem cells show multipotency and self-renewality. We try to utilize these tissue
stem cells in corneal regenerative medicine.
3. Meibomian gland dysfunction.
Meibomian glands secrete lipids into the tear film
and prevent excessive evaporation of the tear film byforming a thin oily layer on the tear film. Meibomian
gland dysfunction (MGD) is a major cause of dry eye
syndrome. We have developed a non-contact, lesstime-consuming, and patient-friendly meibographymethod that employs an infrared filter and an infrared
charge-coupled device (CCD) video camera. Using
this meibography system, the structure of the meibomian glands can be easily observed in both the upper and lower eyelids within 1 minute without causing
any discomfort to the patients. Using this meibography, we are examining the morphologic changes inmeibomian glands associated with aging and sex andassessed their relation with slit-lamp findings of eyelids and tear film function in a normal population.

References
1. Miyata K, Otani S, Miyai T, Nejima R, Amano S.
Atelocollagen punctal occlusion in dry eye patients. Cornea 25:47-50, 2006
2. Yamagami S, Ebihara N, Usui T, Yokoo S, Amano
S. Bone marrow-derived cells in normal humancorneal stroma. Arch Ophthalmol 124:62-69, 2006
3. Hamada N, Kaiya T, Oshika T, Kato S, Tomita G,
Yamagami S, Amano S. Optic disc and retinal
nerve fiber layer analysis with scanning laser tomography after laser in situ keratomileusis. J Re-

4.

5.

6.

7.

8.

fract Surg 22:372-375, 2006
Amano S, Fukuoka S, Usui T, Honda N, Ideta R,
Ochiai M, Yamagami S, Araie M, Awaya Y.
Ocular manifestations of congenital insensitivity
to pain with anhidrosis. Am J Ophthalmol 141:472-477, 2006
Amano S, Honda N, Amano Y, Yamagami
S, Miyai T, Samejima T, Ogata M, Miyata
K.Comparison of central corneal thickness measurements by rotating Scheimpflug camera, ultrasonic pachymetry, and scanning-slit corneal topography. Ophthalmology 113:937-941, 2006
Yokoo S, Yamagami S, Mimura T, Ono K, Amano
S, Saijo H, Mori Y, Takato T. UV-absorption inhuman oral mucosal epithelial sheets for ocularsurface reconstruction. Ophthalmic Res 38:350354, 2006
Mimura T, Funatsu H, Usui T, Yamagami S, Noma
H, Amano S. Topical ocular drug delivery to innerear disease and sinusitis. South Med J 99:12871289, 2006
Osakabe Y, Yaguchi C, Miyai T, Miyata K, Mineo S, Nakamura M, Amano S. Detection of
streptococcus species by polymerase chain reaction in infectious crystalline keratopathy. Cornea
25:1227-1230, 2006

335

University hospital
Medical Information Network(UMIN) Center
Professor
Takahiro Kiuchi, M.D., Ph.D.

Associate Professor
Noriaki Aoki, M.D., Ph.D., M.S., M.B.A.

Homepage

http://www.umin.ac.jp/umin/

Introduction and Organization
The University hospital Medical Information Network (UMIN) (the original name was the University
Medical Information Network), was established in
1989. While general-use computer systems were implemented at all national university hospitals aroundthe end of the Showa era (late 1980s), Dr. Shigekoto
Kaihara, chair and professor at the Hospital Computer
Center, University of Tokyo Hospital, led a project toconnect these computer systems in a network in orderto share information for better communication. Finally,
the Ministry of Education, Culture, Sports, Scienceand Technology approved a budget to initiate the
UMIN Center. The UMIN Center was founded within
the Hospital Computer Center, University of Tokyo
Hospital, and was officially opened in March 1989. Dr.
Tsunetaro Sakurai became an associate professor as
the first full-time UMIN staff. The following are theobjectives of the UMIN Center, as initially outlined in
1989 (No.6 was added later):
1. Provide up-to-date information for healthcare
professionals
2. Promote digitalized communication among
healthcare professionals
3. Support collaborative projects among university
hospitals
4. Support collaborative medical research
5. Standardize data format and support data collec-tion
6. Support medical education and clinical training
The original UMIN system utilized an N1 protocol,
which was developed in Japan and was the only solution at the time to connect general-use computers of
the five major computer vendors in Japan, although it
was poor in function, supporting only line-mode, character-based terminals.
In 1994, we launched a service through the Internet,
and it began to spread in those days. The number of
UMIN users gradually increased, mainly in the E-mailservice.
In 1996, Dr. Takahiro Kiuchi took up a new post
while Dr. Sakurai was promoted to professor at Hokkaido University. Dr, Kiuchi updated the system to be
web-based. With the rapid spread of the Internet in
Japan, UMIN users dramatically increased.
The UMIN Center subsequently started to provide
three major information services: (1) the ELBIS(Electronic Library for Biomedical Sciences) as of1997, (2) the INDICE (Internet Data and Information
Center of Clinical Research) as of 2000, and (3) the
EPOC (Evaluation System of Postgraduate ClinicalTraining) as of 2004.
In April 2002, the UMIN Center became an independent entity, with the adjusted name of University
Hospital Medical Information Network Center, as per
an internal arrangement at the University of Tokyo
Hospital. In 2003, a budget for a new professor posi-336

tion was officially approved by the Ministry of Education, Culture, Sports, Science and Technology. Then,
Dr. Kiuchi was promoted to become the first professorof the UMIN Center on April 1, 2004. On October 1,
2004, Ms. Hisako Matsuba arrived to take on the position of research associate that is a lower part diverted
the associate professor position She resigned from her
position at the end of March, 2006, and Dr. Noriaki
Aoki, formerly an assistant professor at the School of
Health Information Sciences, University of Texas
Health Science Center at Houston, became associate
professor at the Center.

Clinical Activities
Although the UMIN Center is one of the central
medical examination and treatment institutions of the
University of Tokyo Hospital, the center does not provide direct patient care services, but provides services
for medical researchers and practitioners throughout
Japan. We currently have about 250,000 registrants,
and approximately 4,500,000 monthly website accesses, which is currently in the scale of the world’s
highest access rates. The service extends to study /education / medical examination and treatment / hospital duties and encompasses many divergences as
indicated below:
 Research: http://www.umin.ac.jp/research
AC:
Information for Academic Conferences
ELBIS:
Electronic Library for Biomedical
Sciences
FIND:
Fund Information Database
INDICE: Internet Data and Information Centerof Clinical Research
ROCOLS: Recruiting System for Our Colleagues’
and Students’ Education:
http://www.umin.ac.jp/education/
A Web-QME:
Web-based Quality Management System for Education
SUPERCOURSE:
Online Lectures Compiled by Pittsburgh Univ., U.S.A
VHP:
Visible Human Project Image Data
EPOC:
Evaluation System of Postgraduate
Clinical Training

Debut:

Dental Training Evaluation and Tabulation System

 Medical Examination and Treatment
http://www.umin.ac.jp/uhosp/z Intoxication databasez HIV treatment manualz Medical supplies and materials databasez Drug information text database for patientsz Drug information text database for pharmacistsz Standardized nursing procedures databasez Ministry of Education, Culture, Sports, Scienceand Technology document public information
systemz Basic hospital statistics databasez National
university hospital-related medical
dispute reportz Collection of advanced medical procedures applicationz Lists for people and committees
z Various government official appointments, administrative websites and ML
 General Services(1) General information and searchz Medical / biology related websites
z Medical terminologyz A medical research organization / medical institution database(2) Services for information providersz Web service for public
z Web service for membersz Website preservation servicez Video-on-demand (VOD) and streaming service(3) Communication supportz E-mailz Listserv
z News groupz Discussion board
z File exchange

Teaching Activities
We provide lectures and practical instruction in
medical informatics / economics as part of the PhD
program of the Faculty of Medicine. In the undergraduate program, Professor Kiuchi presents a lecture

337

entitled “Medical Literature Informatics.”
We provide briefing sessions and symposiums todisseminate and promote services offered by the
UMIN center. In 2005, the UMIN Center held briefing
sessions and symposiums for medical supplies adverse
event report system, thalidomide registration system,
clinical test registration system, and dental training
evaluation system. In 2006, we held briefing sessions
and symposiums for Safety Management System for
Unapproved Drugs, Individual Case Safety Reports.
These sessions and symposiums were broadcasted
through the MINCS system, and can be downloaded
as VOD from the UMIN server.

Research Activities
The two main characteristics of research studies
conducted through the UMIN Center which distinguish them from studies at other medical informatics
programs, are the following:(1) A focus on health informatics and communication
The Department of Health Communication is
the only research institute in Japan that carries out
health informatics and communication-related research, addressing areas such as the Internet andsatellite communications.
(2) Targeting health information science, not healthcare information practiceCurrently, main topics of research studies atmost medical informatics programs in Japan focus
on information for healthcare practice, such as
hospital information systems, electronic medical
record systems, telemedicine, and electronic billing systems. In contrast, the Department of HealthCommunication has focused on information systems for medical science, such as medical literature databases, data registries for clinical studies,and information systems for medical education.
The following are current research topics at the
Department of Health Communication:(1) Research in Health Communication
Currently, “health communication” is becoming
an important concept in the distribution of clinicalresults for the improvement of population-based
clinical outcomes. We have conducted healthcommunication research focusing on knowledge
and skills in “informatics” and “communication.”(2) Technological Assessment of Health Information
and Communication Technologies
Although information technology is expected toplay an important role in healthcare, its comprehensive usefulness, including cost-effectiveness,has been rarely evaluated. We conducted a literature review in 2003 and concluded that there were
few cost-effectiveness analyses for telemedicine
programs even though many telemedicine programs have been implemented throughout many
developed countries, including the USA and Japan.
Based on the review, we have done a
cost-effectiveness analysis for information technologies.
(3) Edutainment Research
To disseminate clinical knowledge and information to laypersons, it is important to consider
standards such as “easy to understand” and “acceptable by unknowledgeable persons.” We focus
on studies related to media, entertainment, and interface design. For example, we have conducted
the development and evaluation of edutainment
tools for health education aimed at type-1 diabetes
patients, as a concrete application.
(4) Research Regarding Medical Management
It is important to make proper judgments anddecisions in order to achieve optimal outcomes, a
process which is termed “management.” However,scientific research and evaluations related to patient safety, quality improvement and medical
management have not been well established in Japan. We focus on the Theory of Constraint (TOC)
as a tool for medical management from a perspective of information utilization, and conducted research on medical error prevention and quality
improvement.
(5) Research Related to UMIN Activities
Most systems developed at the UMIN Center
have been subjects for research. In particular, we
published and reported systems utilizing advanced
technologies and having scientifically meaningfulconcepts at academic conferences.
(6) Information Systems for Clinical Epidemiologic
Studies
We have developed and applied information

338

systems for clinical epidemiological studies. Recently, we have focused on research in electronic
formats and standardization that are related toclinical research, such as the Clinical Data Interchange Standards Consortium (CDISC). We utilized the achievements attained by the medical research data center at the UMIN.
(7) Research Regarding the Security of an Information
Network
The study addresses a Virtual Private Network(VPN), and secure transactions with electronic
mail (encryption), which have been also utilized
for system management at the UMIN Center.
(8) Research Plan Development; A Statistical Analysisof Clinical Studies
In cooperation with clinicians, we have developed clinical research plans and support statisticalanalysis. In addition, we have done data mining
research for information extraction, knowledge
discovery and prognostic modeling. Furthermore,
we have conducted research and development for
decision support systems to utilize the results inclinical practice.
(9) Patient Registry System for Quality Improvement
Many data have been accumulated in the existing hospital information system, such as electronic
record systems; however, these data have not beenutilized significantly for quality improvement, patient safety or medical management. We have deployed an interactive web-based patient registrysystem with a real-time feedback system of quality
indicators (QIs).

References
1.

2.

Kosuge T, Kiuchi T, Mukai K, Kakizoe T for theJapanese Study Group of Adjuvant Therapy for
Pancreatic Cancer (JSAP). A multicenter randomized controlled trial to evaluate the effect of
adjuvant cisplatin and 5-fluorouracil therapy after
curative resection in cases of pancreatic cancer.
Japanese Journal of Clinical Oncology
36:159-165, 2006
Sano Y, Adachi M, Kiuchi T, Miyamoto T. Effects of nebulized sodium cromoglycate on adultpatients with severe refractory asthma. Respiratory Medicine 100:420-433, 2006

3.

4.

5.

6.

7.

Matsuba H, Kiuchi T, Tsutani K, Uchida E, Ohashi Y. The Japanese perspective on registries anda review of clinical trial process in Japan. Clinical Trial Registries - Practical Guide for Sponsors
and Researchers of Medicinal Products, Birkhäuser Verlag, 83-106, 2006
Kawai S, Hashimoto H, Kondo H, Murayama T,
Kiuchi T, Abe T. Comparison of Tacrolimus andMizoribine in a Randomized Double-Blind Controlled Study in Patients with Rheumatoid Arthritis. Journal of Rheumatology 33(11):2153-2161,
2006
Aoki N, Ohta S, Yamamoto H, Kikuchi N, Dunn
K. Triangulation analysis of tele-palliative care
implementation in a rural community area in Japan. Telemed J E Health 12; 655-62: 2006.
Jibaja-Weiss ML, Volk RJ, Friedman LC, Granchi TS, Neff NE, Spann SJ, Aoki N, Robinson
EK, Beck JR. Edutainment Education for informed breast cancer treatment decision in
low-literate women: Development and initial
evaluation of a patient decision aid. J Cancer
Educ 21; 133-139: 2006.
Jibaja-Weiss ML, Volk RJ, Friedman LC, Granchi TS, Neff NE, Spann SJ, Robinson EK, Aoki
N, Beck JR. Preliminary Testing of a
Just-in-Time, User-Defined Values Clarification
Exercise To Aid Lower Literate Women in Making Informed Breast Cancer Treatment Decisions.
Health Expect 9; 218-231: 2006.

339

Organ Transplantation Service
Director Professor
Masatoshi Makuuchi

Homepage
Organ Transplant Service started to function since2003. In the Western countries the solid organ transplantation is widely performed and in contrast deceased donor organs are extremely rare due to religious and cultural traditions. in Japan the number ofthe recipients from the deceased donors has been limited around 40 under the act of law. The University ofTokyo Hospital has aggressively performed organtransplantation. In 1966, kidney transplantation forchronic renal failure was firstly performed in Japan. In
1996 the living donor liver transplantation was performed and totally 397 patients underwent liver transplantation until March, 2007. The 5-year survival rateis around 85% which is much superior to the national
average (~70%). The University of Tokyo Hospitalhas been one of the authorized institutions for hearttransplantation.

340

Department of Cell Therapy andTransplantation Medicine
Associate Professor
Shigeru Chiba, M.D., Ph.D. (Hematology-Oncology)

Lecturer
Junko Takita, M.D., Ph.D. (Pediatrics/Hematology-Oncology)

Associate
Keiki Kumano, M.D., Ph.D. (Hematology-Oncology)

Homepage

http://www.h.u-tokyo.ac.jp/mukin/index.htm

Introduction and Organization
Department of Cell Therapy and Transplantation
Medicine was institutionally established in 1995, andformally organized in 1996. At present, the staff consists of three medical doctors listed above. Clinicalfacilities include 8 single-patient rooms withhigh-efficiency particulate air filtration and other highstandards. Patients who are eligible for the treatment
with high-grade infectious prophylaxis are admitted to
the facilities.

Clinical activities
Allogeneic hematopoietic stem cell transplantation:
Bone marrow cells are operatively harvested and infused without preservation. For peripheral blood stem
cell transplantation, leukapheresis is performed withthe use of an automated continuous flow blood cell
separator, and harvested cells are preserved at -196°C
in cooperation with Department of Transfusion Medicine. Recently, transplantation after pre-conditioningof reduced intensity (RIST for reduced-intensity stem
cell transplantation or NST for non-myeloabrative
stem cell transplantation) is commonly performed forthe elderly patients and patients with organ damages,
etc. The development of this strategy is expanding theeligibility of transplant recipients.

Several clinical studies with allogeneic stem celltransplantation have been also conducted. These include RIST for pancreatic cancer, transplantation froma donor with mismatched HLA at two loci or more.
All these studies are approved by the ethical committee of the Faculty of Medicine.
High-dose chemotherapy with or without autologous stem cell support: High-dose chemotherapy isadministered according to the malignant disease. For
the autologous stem cell support, peripheral blood
stem cell is usually selected as a source of stem cells.
Similar procedures used in the allogeneic stem cell
harvest are performed for leukapheresis and preservation.
Clinical conference for hematopoietic stem celltransplantation : The conference is held monthly, inwhich the members of Department of Hematology/Oncology and Hematology/Oncology group in the
Department of Pediatrics, and some members of Department of Transfusion Medicine routinely participate and discuss on the patients receiving hematopoietic stem cell transplantation.

Teaching activities
Together with the members of Department of He-

341

matology/Oncology and Hematology/Oncology groupin the Department of Pediatrics, lecture courses on
etiology, pathogenesis, clinical and laboratory features,
differential diagnosis, therapy and prognosis for all
hematological diseases are provided for the second
grade medical students. Courses for bedside learning
on diagnostic and therapeutic issues and arts are given
for the third grade medical students on a man-to-man
basis with a senior faculty member. Clinical clerkshipcourses are given to the fourth grade medical students,
who join the patient care teams consisting of juniorand senior medical doctors and learn medical practices
and patient management, through playing a role as a
junior member of the team, as well as through discussions and presentations.

Research activities
The major research projects are focused on clinicalstudies such as development of improved/new methods for hematopoietic stem cell transplantation, immunotherapy for hematopoietic tumors, and basic
studies on hematopoietic stem cells and leukemogenesis. In the area of pediatric oncology, we continue the studies on molecular mechanisms of pediatric malignancies, such as neuroblastoma, rhabdomyosarcoma, and infant leukemia. Representative publications from our department published in the past two
years are listed in the references.

References(1) Chiba S. Notch signaling in stem cell systems.
Stem Cells 24:2437-2447, 2006
(2) Hosoya N, Sanada M, Nannya Y, Nakazaki K,
Wang L, Hangaishi A, Kurokawa M, Chiba S,
Ogawa S. Genomewide screening of DNA copy
number changes in chronic myelogenous leukemia with the use of high-resolution array-based
comparative genomic hybridization. Genes
Chromosomes Cancer 45:482-494, 2006
(3) Nishiyama U, Yoshino T, Ozai M, Yoshioka R,
Fujisawa M, Ogasawara Y, Kitahori M, Yoshioka
E, Kubo K, Komeno Y, Kurokawa M, Ogawa S,
Chiba S, Osawa T, Kuwaki T, Hirai H, Miwa A.
Antineoplastic effect of a single oral dose of thenovel Flt3 inhibitor KRN383 on xenografted

human leukemic cells harboring Flt3-activating
mutations. Leuk Res 30:1541-1546, 2006
(4) Asano-Mori Y, Kanda Y, Oshima K, Watanabe T,
Shoda E, Motokura T, Kurokawa M, Chiba S.
Pharmacokinetics of ganciclovir in haematopoietic stem cell transplantation recipients with orwithout renal impairment. J Antimicrob Chemother 57:1004-1007, 2006
(5) Nakagawa K, Kanda Y, Yamashita H, Hosoi Y,
Oshima K, Ohtomo K, Ban N, Yamakawa S,
Nakagawa S, Chiba S. Preservation of ovarianfunction by ovarian shielding when undergoing
total body irradiation for hematopoietic stem celltransplantation: a report of two successful cases.
Bone Marrow Transplant 37:583-587, 2006
(6) Haraguchi K, Takahashi T, Nakahara F, Matsumoto A, Kurokawa M, Ogawa S, Oda H, Hirai H,
Chiba S. CD1d expression level in tumor cells is
an important determinant for anti-tumor immunity by natural killer T cells. Leuk Lymphoma
47:2218-2223, 2006
(7) Nakagawa M, Ichikawa M, Kumano K, Goyama
S, Kawazu M, Asai T, Ogawa S, Kurokawa M,
Chiba S. AML1/Runx1 rescues Notch1-null mutation-induced deficiency of para-aortic splanchnopleural hematopoiesis. Blood 108:33293334, 2006
(8) Oshima K, Kanda Y, Nakahara F, Shoda E, Suzuki T, Imai Y, Watanabe T, Asai T, Izutsu K,
Ogawa S, Motokura T, Chiba S, Kurokawa M.
Pharmacokinetics of alemtuzumab after haploidentical HLA-mismatched hematopoietic stem
cell transplantation using in vivo alemtuzumab
with or without CD52-positive malignancies. Am
J Hematol 81:875-879, 2006
(9) Suzuki T, Yokoyama Y, Kumano K, Takanashi
M, Kozuma S, Takato T, Nakahata T, Nishikawa
M, Sakano S, Kurokawa M, Ogawa S, Chiba S.
Highly efficient ex vivo expansion of humanhematopoietic stem cells using Delta1-Fc chimeric protein. Stem Cells 24:2456-2465, 2006(10) Yamashita H, Izutsu K, Nakamura N, Shiraishi K,
Chiba S, Kurokawa M, Tago M, Igaki H, Ohtomo
K, Nakagawa K. Treatment results of chemoradiation therapy for localized aggressive lymphomas: A retrospective 20-year study. Ann
Hematol 85:523-529, 2006

342(11) Chen Y, Takita J, Hiwatari M, Igarashi T, Hanada
R, Kikuchi A, Hongo T, Taki T, Ogasawara M,
Shimada A, Hayashi Y. Mutations of the PTPN11
and RAS genes in rhabdomyosarcoma and pediatric hematological malignancies. Genes Chromosomes Cancer 45:583-591, 2006

340

Department of Cell Therapy andTransplantation Medicine
Associate Professor
Shigeru Chiba, M.D., Ph.D. (Hematology-Oncology)

Lecturer
Junko Takita, M.D., Ph.D. (Pediatrics/Hematology-Oncology)

Associate
Keiki Kumano, M.D., Ph.D. (Hematology-Oncology)

Homepage

http://www.h.u-tokyo.ac.jp/mukin/index.htm

Introduction and Organization
Department of Cell Therapy and Transplantation
Medicine was institutionally established in 1995, andformally organized in 1996. At present, the staff consists of three medical doctors listed above. Clinicalfacilities include 8 single-patient rooms withhigh-efficiency particulate air filtration and other highstandards. Patients who are eligible for the treatment
with high-grade infectious prophylaxis are admitted to
the facilities.

Clinical activities
Allogeneic hematopoietic stem cell transplantation:
Bone marrow cells are operatively harvested and infused without preservation. For peripheral blood stem
cell transplantation, leukapheresis is performed withthe use of an automated continuous flow blood cell
separator, and harvested cells are preserved at -196°C
in cooperation with Department of Transfusion Medicine. Recently, transplantation after pre-conditioningof reduced intensity (RIST for reduced-intensity stem
cell transplantation or NST for non-myeloabrative
stem cell transplantation) is commonly performed forthe elderly patients and patients with organ damages,
etc. The development of this strategy is expanding theeligibility of transplant recipients.

Several clinical studies with allogeneic stem celltransplantation have been also conducted. These include RIST for pancreatic cancer, transplantation froma donor with mismatched HLA at two loci or more.
All these studies are approved by the ethical committee of the Faculty of Medicine.
High-dose chemotherapy with or without autologous stem cell support: High-dose chemotherapy isadministered according to the malignant disease. For
the autologous stem cell support, peripheral blood
stem cell is usually selected as a source of stem cells.
Similar procedures used in the allogeneic stem cell
harvest are performed for leukapheresis and preservation.
Clinical conference for hematopoietic stem celltransplantation : The conference is held monthly, inwhich the members of Department of Hematology/Oncology and Hematology/Oncology group in the
Department of Pediatrics, and some members of Department of Transfusion Medicine routinely participate and discuss on the patients receiving hematopoietic stem cell transplantation.

Teaching activities
Together with the members of Department of He-

341

matology/Oncology and Hematology/Oncology groupin the Department of Pediatrics, lecture courses on
etiology, pathogenesis, clinical and laboratory features,
differential diagnosis, therapy and prognosis for all
hematological diseases are provided for the second
grade medical students. Courses for bedside learning
on diagnostic and therapeutic issues and arts are given
for the third grade medical students on a man-to-man
basis with a senior faculty member. Clinical clerkshipcourses are given to the fourth grade medical students,
who join the patient care teams consisting of juniorand senior medical doctors and learn medical practices
and patient management, through playing a role as a
junior member of the team, as well as through discussions and presentations.

Research activities
The major research projects are focused on clinicalstudies such as development of improved/new methods for hematopoietic stem cell transplantation, immunotherapy for hematopoietic tumors, and basic
studies on hematopoietic stem cells and leukemogenesis. In the area of pediatric oncology, we continue the studies on molecular mechanisms of pediatric malignancies, such as neuroblastoma, rhabdomyosarcoma, and infant leukemia. Representative publications from our department published in the past two
years are listed in the references.

References(1) Chiba S. Notch signaling in stem cell systems.
Stem Cells 24:2437-2447, 2006
(2) Hosoya N, Sanada M, Nannya Y, Nakazaki K,
Wang L, Hangaishi A, Kurokawa M, Chiba S,
Ogawa S. Genomewide screening of DNA copy
number changes in chronic myelogenous leukemia with the use of high-resolution array-based
comparative genomic hybridization. Genes
Chromosomes Cancer 45:482-494, 2006
(3) Nishiyama U, Yoshino T, Ozai M, Yoshioka R,
Fujisawa M, Ogasawara Y, Kitahori M, Yoshioka
E, Kubo K, Komeno Y, Kurokawa M, Ogawa S,
Chiba S, Osawa T, Kuwaki T, Hirai H, Miwa A.
Antineoplastic effect of a single oral dose of thenovel Flt3 inhibitor KRN383 on xenografted

human leukemic cells harboring Flt3-activating
mutations. Leuk Res 30:1541-1546, 2006
(4) Asano-Mori Y, Kanda Y, Oshima K, Watanabe T,
Shoda E, Motokura T, Kurokawa M, Chiba S.
Pharmacokinetics of ganciclovir in haematopoietic stem cell transplantation recipients with orwithout renal impairment. J Antimicrob Chemother 57:1004-1007, 2006
(5) Nakagawa K, Kanda Y, Yamashita H, Hosoi Y,
Oshima K, Ohtomo K, Ban N, Yamakawa S,
Nakagawa S, Chiba S. Preservation of ovarianfunction by ovarian shielding when undergoing
total body irradiation for hematopoietic stem celltransplantation: a report of two successful cases.
Bone Marrow Transplant 37:583-587, 2006
(6) Haraguchi K, Takahashi T, Nakahara F, Matsumoto A, Kurokawa M, Ogawa S, Oda H, Hirai H,
Chiba S. CD1d expression level in tumor cells is
an important determinant for anti-tumor immunity by natural killer T cells. Leuk Lymphoma
47:2218-2223, 2006
(7) Nakagawa M, Ichikawa M, Kumano K, Goyama
S, Kawazu M, Asai T, Ogawa S, Kurokawa M,
Chiba S. AML1/Runx1 rescues Notch1-null mutation-induced deficiency of para-aortic splanchnopleural hematopoiesis. Blood 108:33293334, 2006
(8) Oshima K, Kanda Y, Nakahara F, Shoda E, Suzuki T, Imai Y, Watanabe T, Asai T, Izutsu K,
Ogawa S, Motokura T, Chiba S, Kurokawa M.
Pharmacokinetics of alemtuzumab after haploidentical HLA-mismatched hematopoietic stem
cell transplantation using in vivo alemtuzumab
with or without CD52-positive malignancies. Am
J Hematol 81:875-879, 2006
(9) Suzuki T, Yokoyama Y, Kumano K, Takanashi
M, Kozuma S, Takato T, Nakahata T, Nishikawa
M, Sakano S, Kurokawa M, Ogawa S, Chiba S.
Highly efficient ex vivo expansion of humanhematopoietic stem cells using Delta1-Fc chimeric protein. Stem Cells 24:2456-2465, 2006(10) Yamashita H, Izutsu K, Nakamura N, Shiraishi K,
Chiba S, Kurokawa M, Tago M, Igaki H, Ohtomo
K, Nakagawa K. Treatment results of chemoradiation therapy for localized aggressive lymphomas: A retrospective 20-year study. Ann
Hematol 85:523-529, 2006

342(11) Chen Y, Takita J, Hiwatari M, Igarashi T, Hanada
R, Kikuchi A, Hongo T, Taki T, Ogasawara M,
Shimada A, Hayashi Y. Mutations of the PTPN11
and RAS genes in rhabdomyosarcoma and pediatric hematological malignancies. Genes Chromosomes Cancer 45:583-591, 2006

343

Department of Endoscopy andEndoscopic Surgery
Associate Professor
Takao Kawabe, Ph.D.

Homepage
Introduction and Organization
Department of Endoscopy and Endoscopic Surgery
was established in April 1997. Although the present
staff of our department is only an associate professor,
about 80 doctors of other departments, including thedepartment of internal medicine, surgery, gynecology
and otorhinolaryngology, participate the examinations.The examination rooms moved to the newbuilding in Oct. 2006.

endoscopic biliary stone removal, and endoscopic
stenting for biliary malignant diseases, are recently
increasing. Our recent clinical activities are summarized in Table 1.
Another important activity of our department is thedisinfection and maintenance of endoscopic apparatuses used in other units including outpatient clinic,
radiolographic procedure rooms, surgery rooms or
intensive care units. All endoscopes are collected inour department after use and disinfected.

Clinical activities

Teaching activities

Endoscopic examinations, including upper gastrointestinal endoscopy, colonoscopy, bronchoscopy,
otorhinolaryngological examinations and gynecologycal examinations, are performed from Monday to
Friday. Therapeutic endoscopies, including endoscopic variceal ligation, endoscopic resection including submucosal dissection for esophageal, gastric andcolorectal tumors, polypectomy for colonic polyps,

We participate in under-graduate education as a partof systemic lectures and bed-side learning by the department of gastroenterology, surgery and other departments. As for post-graduate education, training
opportunities for endoscopy and endoscopic surgery
are given to resident or young doctors in a program ofeach department.

Table 1. Enoscopic examinations in Depatment of Endoscopy and Endoscooic Surgery
1997 1998 1999 2000 2001 2002 2003
UGI* endoscopy
Colonoscopy
Bronchoscopy
EUS**
Laparoscopy
Otophino-laryngological examination
Gynecological examination
Total

4384
1398
190
347
19
131
272
6741

5555
2415
239
562
7
96
213
9087

5667
2472
282
569
2
99
153
9244

*UGI; upper gastrointestinal, **Endoscopic ultarasonography

2004

2005

2006

5923 6346 7324 7920 7597 8265 8131
2799 3212 3529 3873 3728 4084 4327
233
194
220
207
194
212
201
438
470
479
583
586
476
461
0
115
154
93
68
61
89
127
149
181
103
124
139
88
58
9689 10566 11852 12778 12195 13199 13282

344

Research activities
Our researches cover a variety of fields including
the upper and lower gastrointestinal tract and the pancreatobilialy system. They are mainly performed incooperation with the department of Gastroenterology.

References
1. Hirano K, Kawabe T, Komatsu Y, Matsubara S,
Togawa O, Arizumi T, Yamamoto N, Nakai Y, Sasahira N, Tsujino T, Toda N, Isayama H, Tada M,
Omata M: High-rate pulmonary involvement inautoimmune pancreatitis. Intern Med J 2006; 36:
58-61.
2. Tanaka Y, Kanai F, Ichimura T, Tateishi K, Asaoka
Y, Guleng B, Jazag A, Ohta M, Imamura J, Ikenoue T, Ijichi H, Kawabe T, Isobe T, Omata M:
The hepatitis B virus X protein enhances AP-1 activation through interaction with Jab1. Oncogene
2006; 25: 633-642.
3. Fujishiro M, Yahagi N, Nakamura M, Kakushima
N, Kodashima S, Ono S, Kobayashi K, Hashimoto
T, Yamamichi N, Tateishi A, Shimizu Y, Oka M,
Ogura K, Kawabe T, Ichinose M, Omata M: Successful outcomes of a novel endoscopic treatment
for GI tumors: endoscopic submucosal dissection
with a mixture of high-molecular-weight hyaluronic acid, glycerin, and sugar. Gastrointest Endosc 2006; 63: 243-249.
4. Wang Y, Kato N, Jazag A, Dharel N, Otsuka M,
Taniguchi H, Kawabe T, Omata M: Hepatitis C
virus core protein is a potent inhibitor of RNA silencing-based antiviral response. Gastroenterology 2006; 130: 883-892.
5. Yamaji Y, Mitsushima T, Ikuma H, Watabe H,
Okamoto M, Yoshida H, Kawabe T, Wada R,
Omata M: Right-side shift of colorectal adenomas
with aging. Gastrointest Endosc 2006; 63: 453464.
6. Hirata Y, Maeda S, Ohmae T, Shibata W, Yanai A,
Ogura K, Yoshida H, Kawabe T, Omata M: Helicobacter pylori induces IkappaB kinase alpha nuclear translocation and chemokine production in
gastric epithelial cells. Infect Immun 2006; 74:1452-1461.

7. Hirata Y, Ohmae T, Shibata W, Maeda S, Ogura K,
Yoshida H, Kawabe T, Omata M: MyD88 and
TNF receptor-associated factor 6 are critical signal transducers in Helicobacter pylori-infected
human epithelial cells. J Immunol 2006; 176:3796-3803.
8. Yoshikumi Y, Mashima H, Suzuki J, Yamaji Y,
Okamoto M, Ogura K, Kawabe T, Omata M: A
case of rectal Dieulafoy's ulcer and successfulendoscopic band ligation. Can J Gastroenterol
2006; 20: 287-290.
9. Hirano K, Kawabe T, Yamamoto N, Nakai Y, Sasahira N, Tsujino T, Toda N, Isayama H, Tada M,
Omata M: Serum IgG4 concentrations in pancreatic and biliary diseases. Clin Chim Acta 2006;
367: 181-184.
10. Fujishiro M, Yahagi N, Nakamura M, Kakushima
N, Kodashima S, Ono S, Kobayashi K, Hashimoto
T, Yamamichi N, Tateishi A, Shimizu Y, Oka M,
Ogura K, Kawabe T, Ichinose M, Omata M: Endoscopic submucosal dissection for rectal epithelial neoplasia. Endoscopy 2006; 38: 493-497.
11. Teratani T, Yoshida H, Shiina S, Obi S, Sato S,
Tateishi R, Mine N, Kondo Y, Kawabe T, Omata
M: Radiofrequency ablation for hepatocellular
carcinoma in so-called high-risk locations. Hepatology 2006; 43: 1101-1108.
12. Tateishi K, Ohta M, Guleng B, Kanai F, Tanaka Y,
Asaoka Y, Jazag A, Imamura J, Imamura T, Ijichi
H, Ikenoue T, Kawakami T, Fukushima Y, Washida M, Sata M, Miyagishi M, Taira K, Yoshida H,
Kawabe T, Omata M: TRAIL-induced cell deathcooperates with IFN-gamma activation in thegraft-versus-tumor effect against colon tumors. Int
J Cancer 2006; 118: 2237-2246.
13. Tanaka Y, Kanai F, Tada M, Asaoka Y, Guleng B,
Jazag A, Ohta M, Ikenoue T, Tateishi K, Obi S,
Kawabe T, Yokosuka O, Omata M: Absence of
PIK3CA hotspot mutations in hepatocellular carcinoma in Japanese patients. Oncogene 2006; 25:
2950-2952.
14. Terai T, Kikuchi K, Iwasawa SY, Kawabe T, Hirata Y, Urano Y, Nagano T: Modulation of luminescence intensity of lanthanide complexes byphotoinduced electron transfer and its application
to a long-lived protease probe. J Am Chem Soc
2006; 128: 6938-6946.

345

15. Fujishiro M, Yahagi N, Kakushima N, Kodashima
S, Muraki Y, Ono S, Yamamichi N, Tateishi A,
Shimizu Y, Oka M, Ogura K, Kawabe T, Ichinose
M, Omata M: Endoscopic submucosal dissectionof esophageal squamous cell neoplasms. Clin
Gastroenterol Hepatol 2006; 4: 688-694.
16. Akamatsu M, Yoshida H, Shiina S, Teratani T, Obi
S, Tateishi R, Mine N, Kondo Y, Kawabe T,
Omata M: Sustained viral response prolonged
survival of patients with C-viral hepatocellular
carcinoma. Liver Int 2006; 26: 536-542.
17. Isayama H, Kawabe T, Nakai Y, Komatsu Y,
Omata M: Covered metallic stents for management of distal malignant biliary obstruction. Dig
Endosc 2006; 18: S110-S111.
18. Isayama H, Nakai Y, Tsujino T, Kawabe T, Omata
M: Which types of drainage tube should we selectfor endoscopic biliary drainage? Current status.
Dig Endosc 2006; 16: S104-S106.
19. Watabe H, Yamaji Y, Okamoto M, Kondo S, Ohta
M, Ikenoue T, Kato J, Togo G, Matsumura M,
Yoshida H, Kawabe T, Omata M: Risk assessment
for delayed hemorrhagic complication of colonicpolypectomy: polyp-related factors and patient-related factors. Gastrointest Endosc 2006;
64: 73-78.
20. Dharel N, Kato N, Muroyama R, Moriyama M,
Shao RX, Kawabe T, Omata M: MDM2 promoter
SNP309 is associated with the risk of hepatocellular carcinoma in patients with chronic hepatitis
C. Clin Cancer Res 2006; 12: 4867-4871.
21. Isayama H, Kawabe T, Nakai Y, Tsujino T, Sasahira N, Yamamoto N, Arizumi T, Togawa O, Matsubara S, Ito Y, Sasaki T, Hirano K, Toda N, Komatsu Y, Tada M, Yoshida H, Omata M: Cholecystitis after metallic stent placement in patientswith malignant distal biliary obstruction. Clin
Gastroenterol Hepatol 2006; 4: 1148-1153.
22. Yamamoto N, Nakai Y, Sasahira N, Hirano K,
Tsujino T, Isayama H, Komatsu Y, Tada M, Yoshida H, Kawabe T, Hiki N, Kaminishi M, Kurosaka H, Omata M: Efficacy of peppermint oil as
an antispasmodic during endoscopic retrograde
cholangiopancreatography. J Gastroenterol Hepatol 2006; 21: 1394-1398.
23. Tsujino T, Isayama H, Sugawara Y, Sasaki T, Kogure H, Nakai Y, Yamamoto N, Sasahira N, Ya-

mashiki N, Tada M, Yoshida H, Kokudo N, Kawabe T, Makuuchi M, Omata M: Endoscopic
management of biliary complications after adultliving donor liver transplantation. Am J Gastroenterol 2006; 101: 2230-2236.
24. Tada M, Kawabe T, Arizumi M, Togawa O, Matsubara S, Yamamoto N, Nakai Y, Sasahira N, Hirano K, Tsujino T, Tateishi K, Isayama H, Toda N,
Yoshida H, Omata M: Pancreatic cancer in patients with pancreatic cystic lesions: a prospective
study in 197 patients. Clin Gastroenterol Hepatol
2006; 4: 1265-1270.
25. Fujishiro M, Yahagi N, Kakushima N, Kodashima
S, Muraki Y, Ono S, Kobayashi K, Hashimoto T,
Yamamichi N, Tateishi A, Shimizu Y, Oka M,
Ogura K, Kawabe T, Ichinose M, Omata M: Successful nonsurgical management of perforation
complicating endoscopic submucosal dissection ofgastrointestinal epithelial neoplasms. Endoscopy
2006; 38: 1001-1006.
26. Ogura M, Yamaji Y, Hikiba Y, Maeda S, Matsumura M, Okano K, Sassa R, Yoshida H, Kawabe T,
Omata M: Gastric cancer among peptic ulcer patients: retrospective, long-term follow-up. Dig
Liver Dis 2006; 38: 811-814.
27. Shibata W, Hirata Y, Maeda S, Ogura K, Ohmae T,
Yanai A, Mitsuno Y, Yamaji Y, Okamoto M, Yoshida H, Kawabe T, Omata M: CagA protein secreted by the intact type IV secretion system leads
to gastric epithelial inflammation in the Mongolian gerbil model. J Pathol 2006; 210: 306-314.
28. Fujishima T, Ishikawa T, Shiratori Y, Kanda M,
Tateishi R, Akamatsu M, Koike Y, Sato S, Obi S,
Hamamura K, Teratani T, Shiina S, Yoshida H,
Kawabe T, Omata M: Age-related comparison of
the profiles of patients with hepatocellular carcinoma. Hepatogastroenterology 2006; 53: 913918.
29. Yamaji Y, Mitsushima T, Yoshida H, Watabe H,
Okamoto M, Wada R, Ikuma H, Kawabe T, Omata
M: The malignant potential of freshly developed
colorectal polyps according to age. Cancer Epidemiol Biomarkers Prev 2006; 15: 2418-2421.
30. Tateishi R, Shiina S, Yoshida H, Teratani T, Obi S,
Yamashiki N, Yoshida H, Akamatsu M, Kawabe T,
Omata M: Prediction of recurrence of hepatocel-

346lular carcinoma after curative ablation using threetumor markers. Hepatology 2006; 44: 1518-1527.
31. Guleng B, Tateishi K, Ohta M, Asaoka Y, Jazag A,
Lin LJ, Tanaka Y, Tada M, Seto M, Kanai F, Kawabe T, Omata M: Smoothened gene mutations
found in digestive cancer have no aberrant Hedgehog signaling activity. J Gastroenterol 2006;
41: 1238-1239.
32. Tateishi K, Ohta M, Kanai F, Guleng B, Tanaka Y,
Asaoka Y, Tada M, Seto M, Jazag A, Lianjie L,
Okamoto M, Isayama H, Tada M, Yoshida H,
Kawabe T, Omata M: Dysregulated expression ofstem cell factor Bmi1 in precancerous lesions of
the gastrointestinal tract. Clin Cancer Res 2006;
12: 6960-6966.

347

Department of
Hemodialysis & Apheresis
Director
Toshiro Fujita, MD, PhD

Vice Director
Head, Eisei Noiri, MD, PhD
Yugo Shibagaki, MD, PhD
Noiri Hanafusa, MD, PhD

Homepage
Introduction

Education

Hemodialysis and related blood purification therapy
had been individually performed in their respective
departments. However, all the departments’ apparatus
and human resources were centralized to form the
Department of Hemodialysis and Center for Hemodialysis in 2000 at the University Hospital. The Centerfor Hemodialysis was further renovated and started
operations in Fall of 2006 as a reference center in ourcountry. This new Center for Hemodialysis isequipped with an infection control unit in addition to
12 hemodialysis machines under a state-of-the-art
hemodialysis control system. Our concept of a hemodialysis controlling system is a hub to transfer all digital and analog data from patients and to monitor machines, including blood purification machines, to thehost computer in our hospital, centralizing all data andadministering medical coding and billing robustly.
Blood purification machines in the ICU are also connectable to this system, which was developed collaboratively with Nihon Kohden Corp. Blood purification machines are selected uniformly to secure patients’ safety while avoiding human error and increasing the overall educational quality of staff members.

1. A systematic review course for M2 students,
which covers clinical features, diagnosis, andevidence-based therapeutic strategies for acuteand chronic renal failure including diabetic nephropathy.
2. Technical development course for medical engineers and nurses.
3. Tutorial course for clinical fellows applying to thespeciality of blood purification therapy.
4. Experiencing hemodialysis & apheresis course forsecond year residents.

Medical Care
1. Start of maintenance hemodialysis therapy forend-stage renal disease (ESRD).
2. Regular hemodialysis therapy for hospitalized
ESRD patients. Please note that our center does
not accept holiday dialysis.
3. Emergency hemodialysis and hemodiafiltration
for ICU patients.
4. Plasma exchange for neurodegenerative diseases,
SLE, TTP, TMA, and pre/post-liver transplant patients.
5. DFPP for collagenous diseases, MG, and dermatological disorders.

348

6. LDL apheresis for nephrotic syndrome and ASO
patients.
7. White blood cell elimination therapy for ulcerative colitis and rheumatological arthritis.

Research
1. Prognostic analysis for post-liver transplant patients received plasma exchange therapy.
2. Development and application of a non-invasive
pulse hemoglobin meter.
3. Candidate gene analysis for CKD; whole genome
analysis for CKD.
4. Elucidation of basic mechanisms in cardio-renal
syndrome and intervention.
5. Pathophysiology of acute renal failure and its applicability for renal regenerative study.
6. Development of a mouse CKD model.
7. Renal biomarker to determine clinical actionability in CKD and type-2 DN.
8. The potentiality of urine biomarker tests for developing country.

References
1. Yamamoto T, Noiri E, Ono Y, Doi K, Negishi K,
Kamijo A, Kimura K, Fujita T, Kinugawa T, Taniguchi H, Nakamura K, Goto M, Shinozaki N,
Ohshima S, Sugaya T: Renal L-type fatty acidbinding protein: possible stress reducer and biomarker for human renal microcirculation. J Am
Soc Nephrol 18: 2894, 2007
2. Negishi K, Noiri E, Sugaya T, Li S, Megyesi J,
Nagothu K, Portilla D: A role of liver fatty acid-binding protein in cisplatin-induced acute renal
failure. Kidney Int 72:348, 2007
3. Hanafusa N, Kondo Y, Suzuki M, Nakao A, Noiri
E, Fujita T: Double filtration plasmapheresis candecrease factor XIII activity. Ther Apher Dial
11:165, 2007
4. Noiri E, Nagano N, Negishi K, Doi K, Miyata S,
Abe M, Tanaka T, Okamoto K, Hanafusa N,
Kondo Y, Ishizaka N, Fujita T: Efficacy of darbepoetin in doxorubicin-induced cardiorenal injury
in rats. Nephron Exp Nephrol 104:e6, 2006
5. Doi K, Noiri E, Fujita T, Tokunaga K:
Non-association of VEGF genetic polymorphism

in promoter—5’ UTR with end-stage renal disease.
Nephrol Dial Transplant 21:1124, 2006
6. Doi K, Noiri E, Nakao A, Fujita T, Kobayashi S,
Tokunaga K: Functional polymorphisms in thevascular endothelial growth factor gene are associated with development of end-stage renal disease in males. J Am Soc Nephrol 17:823, 2006
7. Doi K, Okamoto K, Negishi K, Suzuki Y, Nakao
A, Fujita T, Toda A, Yokomizo T, Kita Y, Kihara Y,
Ishii S, Shimizu T, Noiri E: Attenuation of folic
acid-induced renal inflammatory injury in platelet-activating factor receptor-deficient mice. Am J
Pathol 168:1413, 2006
8. Nishi H, Hanafusa N, Kondo Y, Nangaku M, Sugawara Y, Makuuchi M, Noiri E, Fujita T: Clinicaloutcome of thrombotic microangiopathy after living-donor liver transplantation treated with plasma exchange therapy. Clin J Am Soc Nephrol
1:811, 2006
9. Hanafusa N, Noiri E, Yamashita T, Kondo Y, Suzuki M, Watanabe Y, Kanai T, Miyashita E, Tsuno
NH, Fujii T, Kozuma S, Takahashi K, Taketani Y,
Nakao A, Fujita T: Successful treatment by double
filtrate plasmapheresis in a pregnant woman withthe rare P blood group and a history of multiple
early micharges. Ther Apher Dial 10:498, 2006
10. Noiri E, Kobayashi N, Takamura Y, Iijima T, Takagi T, Doi K, Nakao A, Yamamoto T, Takeda S,
Fujita T: Pulse total-hemoglobinometer provides
accurate noninvasive monitoring. Crit Care Med
33:2831, 2005
11. Noiri E and Tsukahara H: Parameters for measurement of oxidative stress in diabetes mellitus:
applicability of enzyme-linked immunosorbent
assay for clinical evaluation. J Invest Med 53:167,
2005
12. Doi K, Noiri E, Nakao A, Fujita T, Kobayashi S,
Tokunaga K: Haplotype analysis of NAD(P)H
oxidase p22 phox polymorphism in end-stage renal disease. J Hum Genet 50:641, 2005
13. Goligorsky MS, Brodsky SV, Noiri E: NO bioavailability, endothelial dysfunction, and acuterenal failure: new insights into pathophysiology.
Semin Nephrol 24:316, 2004
14. Doi K, Noiri E, Tokunaga K: The association ofNAD(P)H oxidase p22phox with diabetic nephropathy is still uncertain: response to Hodgkinson,

349

Millward, and Demaine. Diabetes Care 27:1518,
2004
15. Doi K, Suzuki Y, Nakao A, Fujita T, Noiri E:
Radical scavenger edaravone developed for clinical use ameliorates ischemia/reperfusion injury in
rat kidney. Kidne Int 65:1714, 2004

350

Clinical Research Center
Professor
Masao Omata, M.D., Ph.D.

Associate Professor
Yoshihiro Arakawa, Ph.D.

Associate
Hirotsugu Watabe, M.D., Ph.D. (Appointed on Dec. 2005)

Homepage

http://www.crc.h.u-tokyo.ac.jp/index.html

Introduction and Organization
The Clinical Research Center was established in
April 2001 as one of the regular departments in thecentral division in our hospital. The Center not only
took over the duties of the former provisional Clinical
Trial Research Center, which dealt industry-initiatedclinical trials, but also newly-incorporated the commission to support investigator-initiated clinical trials.
The staff of the center as of March, 2007, is comprisedof one professor, one associate professor, one associate, six pharmacists, six nurses, one clinical psychologist and three officials, of which two pharmacist andfour nurses were full-time workers with three years'
tenure and two officials and one clinical psychologist
were part-time workers. The center consists of four
subdivisions: a division of consultation on protocol
development (one associate professor and one associate), a division of pharmaceutical administration(three pharmacists), a division of clinical researchcoordination (six nurses, three pharmacists and one
clinical psychologist) and a division of clerkship(three officials).

Clinical activities
The duties of the center are wide-ranging fromserving as a secretariat for the institutional review
board (IRB) to supporting the conduct of clinical trials.
Clinical trials that we dealt with covered all regulatory

clinical trials for approval and investigator-initiatedclinical trials concerned with medicinal treatments.
As an IRB secretariat, to which all the staffs are responsible, we dealt 29 new protocols and 60 ongoingprotocols for industry-initiated clinical trials in fiscal
2006. We also dealt with 1 new protocol for investigator-initiated regulatory clinical trials and 45 investigator-initiated non-regulatory clinical trials, which
include the ethical use of non-approved drugs. A
peer-review meeting was held every month for applications of new industry-initiated protocols to facilitatea review with meaningful discussion in the IRB and to
give practical advice in carrying out the protocols
properly. The meeting was held with the attendance of
applicant company representatives, pre-registered review members from our hospital (pharmacists, doctors,
nurses) and the staffs of the center. We also dealt applications for changes in the initial application documents (362 applications), safety information (561 reports), and other reports in fiscal 2006.
To solve a so-called ‘un-approved drugs issue’ or‘drug lag issue’, participation to global trials was a
key issue. For this purpose, University Hospital Clinical Trial Alliance (UHCT Alliance) comprised of 7
national university hospitals (Tokyo University, Niigata University, Gunma University, Shinshu University, Tsukuba University, Tokyo Medical and Dental
University and Chiba University) was established in2006 and is collaborating with each other in continuing improvement of our clinical trial environments. In
fiscal 2006, 10 protocols was introduced to the alli-

351

ance including 5 multi-national trials.
As for pharmaceutical administration, we tookcharge of 98 clinical trial drugs and filled 1391 prescriptions in fiscal 2006. Pharmacists in the division
are also in charge of the primary review of safety information about clinical trial drugs and the databasemanagement in the Center. Our databases concerning
protocols and subjects were transferred to a new system as a part of the hospital clinical information system in March 2006, allowing the direct access to theclinical trial information from the hospital system.
Clinical research coordinators (CRC) supported theimplementation of all the ongoing regulatory clinical
trials in fiscal 2006. The coordination covered all aspects in pursuing clinical trials: preparation for thetrials, screening for patients, assistance to obtain patients’ informed consent, coordinating outpatients’visit, assistance with inspections, assistance in the
preparation of case report forms (CRF), arrangements
for monitoring and audits, and arrangements for medical accounting. There were a total of 3777 times ofcoordination of outpatients' visits and medical treatments of inpatients in fiscal 2006. CRC also supported
the implementation of four investigator-initiatednon-regulatory clinical trials partly. In 2005, we introduced a principle that beneficiaries should pay forpart of a personnel cost of CRCs and adopted two investigator-initiated protocols for the CRC support on
this principle.
Publicity activity has been continued including theprovision of the information about the protocols undersubject recruitment both in our internet home pageand in our takeaway leaflets.
The outpatient clinic dedicated for clinical trials
moved new building in Nov. 2006 and was newly
equipped with consultation counters and a waitingroom.
The consultation division started in May 2002 to
support the investigator-initiated clinical trial. The
mission of the division is to help investigators to
conduct clinical research under the ethically and scientifically reviewed protocols. Namely, the division
supports protocol development, application to IRB
and monitoring of the progress and amendment ofclinical trials. As for educational programs of clinicalresearch for investigators, the division also gives a
training course 3 to 4 times a year and a symposium

every year. The division dealt with 45 investigator-initiated clinical trials which include the ethicaluse of non-approved drugs in fiscal 2006.

Teaching activities
The Center accepted 50 fourth grade students fortraining in collaboration with the Pharmaceutical Department. Arakawa is taking charge of one half-year
lecture on clinical pharmacology for the graduate
course students in the Faculty of Pharmaceutical Sciences every year. One graduate student belonged toour research labs in fiscal 2006.
The Center is involved as an on-the-job training institution in CRC training programs. In fiscal 2006, we
accepted 3 one-week trainees from the program operated by Pharmacist Training Center.

Research activities
We performed the publication of 4 original papers
written in English, 4 original papers in Japanese, 6
review papers in Japanese and one textbook for clinical trials and the 26 presentations in academic conferences in 2006. We submitted a patent application
for a new method for medicinal treatment for amyotrophic lateral sclerosis.

References(1) Morisawa Y, Takayama S, Okushi K, Nakamura T,
Fukuda K, Arakawa Y, and Toyama Y. Quantitation of neurotrophin mRNA in skeletal muscle:
Changes during the process of peripheral nerve
regeneration. J. Musculoskeletal Res. 2006;10:131-140.
(2) Watabe H, Yamaji Y, Okamoto M, Kondo S, Ohta
M, Ikenoue T, Kato J, Togo G, Matsumura M,
Yoshida H, Kawabe T, Omata M. Risk assessment
for delayed hemorrhagic complication of colonicpolypectomy; polyp-related factors and patient-related factors. Gastrointest Endosc. 2006;
64:73-8.
(3) Yamaji Y, Mitsushima T, Ikuma H, Watabe H,
Okamoto M, Yoshida H, Kawabe T, Wada R,
Omata M. Right-side shift of colorectal adenomas
with aging. Gastrointest Endosc. 2006;63:453-8.

352(4) Yamaji Y, Mitsushima T, Yoshida H, Watabe H,
Okamoto M, Wada R, Ikuma H, Kawabe T, Omata
M. The malignant potential of freshly developed
colorectal polyps according to age. Cancer Epidemiol Biomarkers Prev. 2006;15:2418-21.
(5) Arakawa Y. Back ground of the establishment andthe current status of University Hospital Clinical
Trial Alliance (UHCT Alliance). Gekkan Yakuji
2006;48:1915-1921.
(6) Ohashi Y and Arakawa Y eds. How to conduct
clnical trials. Nanko-do, Tokyo, 2006.

353

Division of Tissue Engineering
Director & Professor
Tsuyoshi Takato, M.D., Ph.D.

Visiting Associate Professors
Ung-il Chung, M.D., Ph.D. (Vice Director), Keiichi Hishikawa, M.D., Ph.D.,
Kazuto Hoshi, M.D., Ph.D.,
Hiroyuki Koyama, M.D., Ph.D.,
Seishi Ogawa, M.D., Ph.D.,
Satoru Yamagami, M.D., Ph.D.

Visiting Research Associates
Toshiyuki Ikeda, M.D.,
Toru Ogasawara, D.D.S., Ph.D.,
Makoto Ohba, Ph.D.,
Seiichi Yokoo, Ph.D.,

Homepage

Takeshi Marumo, M.D., Ph.D.,
Naoshi Ogata, M.D., Ph.D.,
Takahiro Suzuki, M.D., Ph.D.,

http://square.umin.ac.jp/t-e/

Introduction and Organization
Division of Tissue Engineering was established as a
special medical office in The University of Tokyo
Hospital, in October 2001 and has a fully equipped
800 m2 laboratory on the 8th floor of the Inpatient
Word B. Division of Tissue Engineering consists of
Department of Bone ＆ Cartilage Regenerative
Medicine (Takeda Chemical Industries, Ltd.), Department of Vascular Regeneration (Daiichi Pharmaceutical Co), Department of Regeneration Medicine
for Hematopoiesis (Kirin Brewery Co., Ltd.), Department of Corneal Tissue Regeneration (ArBlast Co.,
Ltd.), Department of Clinical Renal Regeneration(Mochida Pharmaceutical Co., LTD.), Department of“ Fujisoft ABC” Cartilage & Bone Regeneration(FIJISOFT ABC INCORPORATED.). We have invited talented personnel of various fields from home
and abroad. One visiting associate professor and one
or two visiting research associates who are assigned toeach department are conducting research with many
post graduate students. Aiming at clinical application
within a few years, the researchers continue their studies to make the center function as a translational research center.

Tie-up with companies, technical transfer, patenting
developed technologies, producing materials fortreatment at a GMP level, safety evaluation studies
and organization for clinical trials are necessary inorder to realize regenerative medicine, which is now
recognized as a national project. As foundation andoperation of venture companies as well as industry-university-government cooperation is essential to
the success, it seems that state-level efforts are necessary. It is expected that broad progress in tissue engineering technologies and regenerative medicine contributes to treatment and drug discovery of all medical
fields regardless of specialties.
October, 2001 Division of Tissue Engineeringfounded as special medical office in the Universityof Tokyo Hospital.
June, 2002 Department of Corneal Tissue
Engineering founded by a donation from HOYA healthcare CO., Ltd.
July, 2002 Department of Vascular Regeneration
founded by a donation from Daiichi PharmaceuticalCo., Ltd.
July, 2002 Department of Bone & Cartilage Regenerativen Medicine founded by a donation from
TAKEDA Chemical Industries., Ltd.

354

September, 2002 Department of Regeneration medicine for Hematopoiesis founded by a donation fromKIRIN Brewery Co., Ltd.
November, 2002 Department of Clinical Renal Regeneration founded by a donation from MOCHIDA
Pharmaceutical Co., Ltd.
November, 2002 Department of MENICON Cartilage & Bone Regeneration founded by a donationfrom MENICON Co., Ltd.
March, 2003 The Cell Processing Center set up on
the 8th floor of the Inpatients Ward B.
June, 2005 Department of Corneal Tissue Regeneration was renewed by a donation from AMNIO TEC
Co., Ltd (now ArBlast Co., Ltd.)
July, 2005 Department of Bone & Cartilage Regenerative Medicine was renewed by a donation from
TAKEDA Chemical Industries, Ltd.
September, 2005 Department of Regeneration
Medicine for Hematopoiesis was renewed by a donation from KIRIN Brewery Co., Ltd.
November, 2005 Department of Clinical Renal Regeneration was renewed by a donation fromMOCHIDA Pharmaceutical Co., Ltd.
November,2005 By a donation from FUJISOFTABC Co., Ltd. Department of MENICON Cartilage &Bone Regeneration was renewed to Department ofFuji Software ABC Cartilage & Bone Regeneration.

Research activities
As for corneal regeneration, we aim at constructionof regenerated cornea, clinical application of corneal
epithelial sheet transplantation for ocular surface reconstruction and establishment and clinical application of corneal endothelium transplantation. To
achieve these goals, we are conducting functional
analysis on cultured corneal cells, reconstruction of
cornea with cultured epithelium and endothelium, andartificial stroma, research on adult stem cell biology incorneal tissues and immunological analysis on amniotic membrane for ocular surface reconstruction
As for vascular regeneration, we aim at establishment of effective and safe “therapeutic angiogenesis”
and its clinical application, development of non-invasive
soft-tissue reconstruction technique assisted by induction of angiogenic reactions and development of thetechniques to induce microcirculation to regeneratedorgans. To achieve these goals, we are conducting research on angiogenic gene therapy using adenovirus
vector, research on angiogenic gene therapy using
non-viral vector, development of drug delivery method for therapeutic angiogenesis and research on induction of angiogenic reactions in soft-tissue.
As for bone and cartilage regeneration, we aim todevelop easy, precise, non-invasive systems to detect
osteoblastic and chondrocytic differentiation, to determine a finite set of signaling factors sufficient for
induction of osteoblasts and chondrocytes, to develop
a cell-sheet culture system for bone and cartilage, todevise a method to induce osteogenesis and angiogenesis simultaneously, to screen for compounds thatinduce bone and cartilage regeneration, to develop
non-viral gene transfer methods by nano-micelletechnology and to generate and transplant regenerated
bone and cartilage. To achieve these goals, we areconducting research on bone and cartilage biology,
developmental biology, stem cell biology and regenerative medicine.
As for renal regeneration, we aim at clinical application of kidney-derived adult stem cell, clinical application of new scaffold material and matrix for renal
regeneration and clinical renal regeneration by using
cord blood. To achieve these goals, we are conducting
research on adult stem cell biology in regeneration,
comprehensive research on stem cell dysfunction inrenal failure and development of 3-D culture system
for induction of metanephros in vitro.
As for regenerative medicine for hematopoiesis, we
aim to develop effective systems for in vitro expansion of cord blood hematopoietic stem cells(CB-HSCs) and its clinical application to human hematopoietic stem cell transplantation, and for inducing
various hematopoietic components from HSCs andembryonic stem cells. To achieve these goals, we areconducting research on the regulatory mechanisms ofproliferation, self-renewal, and differentiation of human hematopoietic stem cells (HSCs), plasticity of
HSCs and clinical application of the in vitro expansion and differentiation system of HSCs.
In the department donated by FUJISOFT ABC, we
aim to produce regenerated cartilage and bone withhigh safety and usefulness, to realize production system and establish practical quality control and topromote the application of regenerated cartilage and355bone. To achieve these goals, we are conducting research on adult stem cell biology in mesenchymal tissues, application of molecular biology on cartilage
repair for regenerative medicine, development of novel scaffolds in cartilage and bone regeneration, development of 3-D reconstruction system for regenerated
tissues, evaluation on biochemical and biophysicalproperties of regenerated tissues in vivo and clinical
trials and application of regenerated cartilage andbones.
Basic Research on human ES cells
Besides, to promote basic research on human embryonic stem cells with our eyes set on applications in
the future, Department of Clinical Renal Regeneration
and Department of Bone and Cartilage Regenerative
Medicine are carrying forward the application procedures to obtain human ES cells from Institute for
Frontier Medical Sciences, Kyoto University, which
will be approved shortly.
Clinical Studies
Of particular note is clinical studies started in thefour departments as a result of basic research. In Department of Regenerative Medicine for Hematopoiesis,
clinical study on expansion of human cord blood hematopoietic cells (Institutional Review Board approval number #351) has been started. In Departmentof Vascular Regeneration, clinical studies on claudication limbs and severe ischemic limbs caused by peripheral vascular diseases (IRB approval number #825
and #826) have been started and continued withoutcausing major side effects. In Department of Corneal
Tissue Regeneration, clinical studies on transplantation of cultured autologous oral mucous epithelial
sheet on amniotic membrane for ocular surface reconstruction, and corneal endothelial stem cell transplantation for decrease in number of corneal endotheliums(IRB approval number #363 and #898) have been
started. In Department of Bone & Cartilage Regenerative Medicine, clinical study on bone implants into
non-loading parts (IRB approval number #1310) will
be started by the end of March. As stated above, weare proceeding translational research aiming at clinicalapplication of tissue engineering and regenerative
medicine.

Contribution to the Hospital
Division of Tissue Engineering, as a cooperative
research facility in the Hospital, opens expensive special machines that each laboratory cannot afford toequip with, such as a confocal laser scanning microscope, a cell analyzer and a cell sorter to the Hospital
staff, letting them use with cost sharing. Department
of Plastic Surgery is conducting research using thisfacility.

References
1. Nakagawa M, Ichikawa M, Kumano K, Goyama
S, Kawazu M, Asai T, Ogawa S, Kurokawa M,
Chiba S. AML1/Runx1 rescues Notch1-Nullmutation- induced deficiency of para-aortic
splanchnopleural hematopoiesis. Blood 2006;
108: 3329-3334.
2. Suzuki T, Yokoyama Y, Kumano K, Takanashi M,
Kozuma S, Takato T, Nakahata T, Nishikawa M,
Sakano S, Kurokawa M, Ogawa S, Chiba
S. Highly efficient ex vivo expansion of humanhematopoietic stem cells using Delta1-Fc chimeric protein. Stem Cells 2006;24:2456-2465.
3. Hosoya N, Sanada M, Nannya Y, Nakazaki K,
Wang L, Hangaishi A, Kurokawa M, Chiba S,
Ogawa S Genomewide screening of DNA copy
number changes in chronic myelogenous leukemia with the use of high- resolution arraybased comparative genomic hybridization.Genes
Chromosomes Cancer 2006;45:482-494.
4. T. Miyahara, H. Koyama, T. Miyata, H. Shigematsu, J. Inoue, T. Takato, H. Nagawa. Inflammatory responses involving tumor necrosis factor
receptor-associated factor 6 contribute to in-stentlesion formation in a stent implantation model of
rabbit carotid artery. Journal of Vascular Surgery,2006; 43, 592-600.
5. Igawa K,Mochizuki M,Sugimori O,Shimizu
K,Yamazawa K,Kawaguchi H, Nakamura
K,Takato
T,Nishimura
R,SuzukiS,Anzai
M,Chung U,Sasaki N. Tailor-made tricalcium
phosphate bone implant directly fabricated by athree-dimensional ink-jet printer 2006; J Artif
Organ 9:234-240.
6. Bounoutas GS, Tawfeek H, Fröhlich LF, Chung
U, Abou-Samra AB. Impact of impaired recep-

356

tor internalization on calcium homeostasis inknock-in mice expressing a phosphorylationdeficient parathyroid hormone (PTH)/PTHrelated peptide receptor. Endocrinology 2006;
147: 4674-4679.
7. Kanayama N, Fukushima S, Nishiyama N, Itaka
K, Jang W, Miyata K, Yamasaki Y, Chung U,
Kataoka K. A PEG-Based Biocompatible Block
Catiomer with High Buffering Capacity for theConstruction of Polyplex Micelles Showing Efficient Gene Transfer toward Primary Cells.
ChemMedChem 2006;1: 439-444.
8. Guo J, Chung U, Yang D, Karsenty G, Bringhurst
R, Kronenberg HM. PTH/PTHrP receptor delays
chondrocyte hypertrophy via both Runx2dependent and -independent pathways. Dev Biol
2006;292: 116-128.
9. Yamada T, Kawano H, Koshizuka Y, Fukuda T,
Yoshimura K, Kamekura S, Saito T, Ikeda T,
Kawasaki Y, Azuma Y, Ikegawa S, Hoshi K,
Chung U, Nakamura K, Kato S, Kawaguchi H.
Carminerin contributes to chondrocyte calcification during endochondral ossification. Nat Med
2006；12: 665-670.
10. Kugimiya F, Ohba S, Nakamura K, Kawaguchi H,
Chung U. Physiological role of bone morphogenetic proteins in osteogenesis. J Bone Miner
Metab 2006; 24: 95-99.
11. Shinoda Y, Yamaguchi M, Ogata N, Akune T,
Kubota N, Yamauchi T, Terauchi Y, Kadowaki T,
Takeuchi Y, Fukumoto S, Ikeda T, Hoshi K,
Chung U, Nakamura K, Kawaguchi H. Regulation of bone formation by adiponectin throughautocrine/paracrine and endocrine pathways. J
Cell Biochem 2006; 99: 196-208.
12. Katagiri M, Ogasawara T, Hoshi K, Chikazu D,
Kimoto A, Noguchi M, Sasamata M, Harada S,
Akama H, Tazaki H, Chung U, Takato T, Nakamura K, Kawaguchi H. Suppression of adjuvant-induced arthritic bone destruction by cyclooxygenase-2 selective agents with and without
inhibitory potency against carbonic anhydrase II.
J Bone Miner Res 2006; 21: 219-227.
13. Yamaoka H, Asato H, Ogasawara T, Nishizawa S,
Takahashi T, Nakatsuka T, Koshima I, Nakamura
K, Kawaguchi H, Chung U, Takato T, Hoshi K.
Cartilage tissue engineering using human auri-cular chondrocytes embedded in different hydrogel materials. J Biomed Mater Res A 2006;
78: 1-11.
14. Kamekura S, Kawasaki Y, Hoshi K, Shimoaka T,
Chikuda H, Maruyama Z, Komori T, Sato S, Takeda S, Karsenty G, Nakamura K, Chung U,
Kawaguchi H: Contribution of runt-related transcription factor 2 to pathogenesis of osteoarthritis in mice after induction of knee joint instability.
Arthritis Rheum 54 2006; 2462-2470.
15. Zhao B, Katagiri T, Toyoda H, Takada T, Yanai T,
Fukuda T, Chung U, Koike T, Takaoka K, Kamijo R. Heparin potentiates the in vivo ectopic
bone formation induced by bone morphogenetic
protein-2. J Biol Chem 2006;281: 23246-23253.
16. Provot S, Kempf H, Murtaugh C, Chung U, Kim
DW, Chyung J, Kronenberg HM, Lassar AB.
Nkx3.2/Bapx1 acts as a negative regulator ofchondrocyte maturation. Development 2006; 133(4):651-662.
17. Yoshikawa M, Hishikawa K, Marumo T, Fujita
T.Inhibition of histone deacetylase activity suppresses epithelial-to-mesenchymal transition induced by TGF-beta1 in human renal epithelial
cells.J Am Soc Nephrol. 2007 Jan;18(1):58-65.
18. Hishikawa, K., and Fujita, T. 2006. Stem cells
and kidney disease. Hypertens Res 29:745-749.
19. Marumo, T., Uchimura, H., Hayashi, M., Hishikawa, K., and Fujita, T. 2006. Aldosterone impairs bone marrow-derived progenitor cell formation. Hypertension 48:490-496.
20. Hirahashi, J., Mekala, D., Van Ziffle, J., Xiao, L.,
Saffaripour, S., Wagner, D.D., Shapiro, S.D.,
Lowell, C., and Mayadas, T.N. 2006. Mac-1 signaling via Src-family and Syk kinases results inelastase-dependent thrombohemorrhagic vasculopathy. Immunity 25:271-283.
21. Zeller, G.C., Hirahashi, J., Schwarting, A.,
Sharpe, A.H., and Kelley, V.R. 2006. Inducible
co-stimulator null MRL-Faslpr mice: uncouplingof autoantibodies and T cell responses in lupus. J
Am Soc Nephrol 17:122-130.
22. Yamagami S, Ebihara N, Usui T, Yokoo S,
Amano S. Bone marrow-derived cells in normal
human corneal stroma. Arch Ophthalmol 2006;
124;62-69.
23. Amano S, Fukuoka S, Usui T, Honda N, Ideta R,

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Ochiai M, Yamagami S, Araie M, Awaya Y.
Ocular manifestations of congenital insensitivity
to pain with anhidrosis. Am J Ophthalmol 2006;
141:472-477.
24. Kinouchi R, Kinouchi T, Hamamoto T, Saito T,
Tavares A, Tsuru T, Yamagami S. Distribution of
CESP-1 protein in the corneal endothelium andother tissues. Invest Ophthalmol Vis Sci 2006;
47: 1397-1403.
25. Hamada N, Kaiya T, Oshika T, Kato S, Tomita G,
Yamagami S, Amano S. Optic disc and retinal
nerve fiber layer analysis with scanning laser
tomography after LASIK. J Refract Surg 2006;
22:3372-375.
26. Amano S, Honda N, Amano Y, Yamagami
S, Miyai T, Samejima T, Ogata M, Miyata K.
Comparison of central corneal thickness measurements by rotating Scheimpflug camera, ultrasonic pachymetry, and scanning-slit corneal
topography. Ophthalmology 2006;113:937-941.
27. Yokoo S, Yamagami S, Mimura T, Ono K, Amano S, Saijo H, Mori Y, Takato T. UV-absorption
in human oral mucosal epithelial sheets for ocular surface reconstruction. Ophthalmic Research
2006;38:347-351.
28. Mimura T, Funatsu H, Usui T, Yamagami S,
Noma H, Amano S. Topical ocular drug delivery
to inner ear disease and sinusitis. South Med J
2006;99:1287-1289.

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Hospital Planning andManagement
Associate Professor
Tomoaki Imamura, M.D.

Associate
Hideo Yasunaga, M.D., Hiroo Ide, M.A.

Homepage

http://www.cc.h.u-tokyo.ac.jp/mulins/kikakushitsu/index.htm

Introduction and Organization

Clinical activities

In recent years, the medical system in Japan has
been experiencing times of major change. University
hospitals, as well, have been under pressure forsweeping reforms. There are demands, greater thanever before, for the development and practical application of high-quality advanced medical treatment,
and for the efficient promotion of graduate and postgraduate education, and of clinical research. And there
are demands for those results to be expressed clearly
to Japanese citizens in specific terms. In April 2004,
as the University of Tokyo was incorporated under the
National University Corporation Law, the Universityof Tokyo Hospital underwent drastic organizational
restructuring. In addition to the establishment of Hospital Executives, there was also the launch of fourorganizations that support hospital management (Hospital Planning and Management; Personnel Administration and Human Resources; Performance Monitoring, Risk Management, and Staff Development; andEducation and Research Support) and three organizations that support clinical management (Inpatient Service Administration; Outpatient Service Administration; and Central Hospital Service Administration).
Hospital Planning and Management is a key working organization in the management of the hospital. It
has three full-time instructors from the Department ofPlanning, Information and Management, and boasts ateam of two pharmacists, two nurses, one engineering
staff member, and ten administrative staff.

Hospital Planning and Management is responsible
for all of the organizational and strategic business affairs of the University of Tokyo Hospital. It conducts
the following kinds of clinical-management duties.
(1) Analysis of hospital management
The division manages and analyzes hospital accounting information, and conducts hospitalmanagement analyses by utilizing management
information and standardized hospital information.
(2) Planning and strategy
Based on the hospital management analyses, thedivision designs short-term management planningand strategy proposals, and provides effective
support for the Hospital Executives to make swift
management decisions. The division is also responsible for formulating medium- and long-termplans. Following is a list of hospital management
achievements in which Hospital Planning andManagement was deeply involved.
・ Launched the “22nd Century Medical Center”
・ Launched the new central hospital wing
・ Enhanced functions in the inpatient ward (expansion of ICU/CCU, increase in number ofbeds in the Psychiatry Department)
・ Reduced the average length of hospital stays,
and improved the bed occupancy rate
・ Achieved reductions in medication costs andcosts for medical materials

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In addition to these achievements, the division
has also strived to improve innovative patient
services, such as introducing a credit card forpatients, attracting commercial stores to set up
in the hospital, and illuminating the hospitalbuildings. At the same time, the division has
worked to develop an environment in which
medical care staff can provide high-quality andsafe medical treatment in a more composed
fashion.
(3) Medical policy recommendations
The division is not just restricted to the management of the University of Tokyo Hospital. It also
actively implements policy recommendations
aimed at improving the medical system in Japanand at deregulating medical care.
Furthermore, we point out issues related to Japan’s medical insurance system based on evidence, and we constantly issue messages for theirimprovement.

Teaching activities
Turning to postgraduate education, the division accepts one doctoral student from the Department ofMedical Informatics and Economics at the Graduate
School of Medicine, and one master’s student and one
research student from the Department of Clinical
Bioinformatics Research Unit at the Graduate Schoolof Medicine.
Postgraduate students and research students pursue
their own research projects, not just from the researchareas of healthcare management and hospital management, but also from such areas as healthcare economics and healthcare policy. The students review
previous literature and materials, and they are actively
engaged in developing research designs and the collection of data. The students present regular research
progress reports, they are given thorough instruction
on writing academic papers, and they also follow arigid schedule of academic presentations.

Research activities
The research activities of the division are not limited to merely healthcare management and hospitalmanagement, but cover a broader area, including

healthcare policy and healthcare economics.
（1） Research in healthcare management
The division analyzed the impact that a prospective payment system, which is based on Diagnosis Procedure Combination (DPC), has on thehealthcare workplace, and it conducted researchto estimate the effects that this system has on thelength of hospital stays.
The division also conducted research related tothe efficient use of medical facilities, by studying
the relationship between the running of operatingrooms and the number of hospital beds.
In an attempt to systemize healthcare management, the division edited a standard textbook. The
division is also conducting research into the development of an education program for healthcare
management.
(2) Research in healthcare policy
The division carried out assessments related toJapan’s medical insurance system, and in particular, conducted research into improvements tothe prospective payment system based on DPC,
and the effectiveness of such improvements.
The division is also undertaking comparative studies between medical systems in Japan and otherdeveloped countries, as well as empirical studies
related to the disparity of domestic and imported
prices of medical equipment, and studies into thecareer paths of medical doctors.
(3) Research in healthcare economics
Using the contingent valuation method, the division is carrying out research related to the benefit
evaluation of healthcare services. The division is
also running empirical studies on the distributive
efficiency of healthcare services, using cost analyses and cost-benefit analyses.
In addition, the division is also conducting economic analyses related to the effects that thepromotion of preventative medicine has had oncontrolling national medical expenses.
Furthermore, the division is also conducting
economic analyses on medical safety (research on
cost analysis of medical accidents, and analysis
on the cost effectiveness of medical safety measures).
(4) Health-related risk analysis and research
Risk analysis is comprised of risk assessment,

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risk management, and risk communication, and is
a new approach for minimizing all kinds of damage. Based on this technique, the division is investigating and analyzing what exactly is necessary to minimize damage caused by incidents involving health risks. In recent years, there has
been a rising necessity for the protection of citizens from the threat of terrorism. We have been
conducting research to develop effective measures, especially against foodborne bioterrorism
and chemical terrorism. Furthermore, in light of
the globalization of recent years, a key issue has
been food safety standards—the bringing into
synch of the standards of individual countries,
and the development of unified international
standards. International standards are deliberated
and determined at the Codex Alimentarius Commission (CAC). We use the risk analysis approach to study the various issues related to foodsafety which are discussed at the CAC.
In terms of risk communication, we conduct research on the disparities between the public information released by government agencies andthe information circulated by the media. We also
conduct research on risk communication for
managing crises during times of health hazards.
Furthermore, for the purpose of empirically clarifying whether risk communication can actually
reduce damage, we are investigating and studying
the effect that displaying allergy-causing substances on food packaging has on reducing incidences of food allergies.
(5) Research into health statistics
The division conducts a great deal of healthcare-related statistical research and analysis. Oneof these is a cohort study on Kanemi rice oil poisoning. Recently, thanks to improvements in verification technology, it has become possible tomeasure the concentration of dioxins in the
blood. We are conducting investigations and research on the relationship between the concentration of dioxins in the blood of patients with
Kanemi rice oil poisoning and their clinicalsymptoms.
We are also conducting resident surveys to ascertain the actual facts on allergy diseases andsymptoms, as well as follow-up surveys to inves-tigate the allergy-causing substances.

References
1. Yasunaga H, Ide H, Imamura T, Ohe K: Influence ofJapan'sNew

Diagnosis

Procedure

Combina-tion-Based Payment System on the Surgical Sector:
Does it Really Shorten the Hospital Stay? Surgery
Today, 36(7), 577-585, 2006
2.

Yasunaga H, Ide H, Imamura T, Ohe K: The Measurement of Willingness to Pay for Mass Cancer
Screening with Whole-Body PET (Positron Emission Tomography) Annals of Nuclear Medicine, 20(7), 457-462, 2006

3.

Yasunaga H, Ide H, Imamura T, Ohe K: Benefit
evaluation of mass screening for prostate cancer:
willingness-to-pay measurement using contingent
valuation Urology 68(5), 1046-1050, 2006

4.

Yasunaga H, Ide H, Imamura T, Ohe K. Willingness
to pay for health care services in common cold, retinal detachment, and myocardiac infarction: an Internet survey in Japan. BMC Health Services Research 2006; 6: 12.

5.

Yasunaga H, Ide H, Imamura T, Ohe K. Analysis of
the factors affecting willingness to pay for the medical services of cardiovascular diseases. International
Heart Journal 2006; 47(2) 273-286.

6. Yasunaga H, Ide H, Imamura T, Ohe K. Medical
research using Internet questionnaire in Japan.
(in Japanese) Japanese Journal of Public Health2006; 53(1): 40-50.
7. Imamura T, Yasunaga H, Ide H. Iryo-Keiei-Gaku.
(in Japanese) Tokyo: Igaku-Shoin; 2006

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Department of Child Psychiatry
Professor
Nobumasa Kato, M.D.,Ph.D.

Specially Appointed Associate Professor
Yukiko Kano, M.D.,Ph.D.

Specially Appointed Lecturer
Keiichiro Watanabe, M.D., Ph.D.

Specially Appointed Associate
Soo-Yung Kim, M.D.

Homepage

http://kokoro.umin.jp/

Introduction and Organization

Clinical activities

The Department of Child Psychiatry was established in April 2005 as the clinical counterpart to theClinical Education Center of Mental Development,
both of which are funded by the special grant for faculty development. The major aim of the Clinical Education Center is to train mental health specialists invarious fields with a fundamental grounding in childpsychiatry and neurosciences. Much of the services
provided are based on the 37 years of experience inintervention and treatment for developmentally disabled children established in the former child psychiatry division of Department of Neuropsychiatry.
The department uses a multidisciplinary approach byworking in collaboration not only with the Departmentof Neuropsychiatry, Department of Pediatrics andGraduate School of Education in the University ofTokyo but also several other educational and/or clinical facilities on mental development or developmental
disorders. The Department of Child Psychiatry complements the Clinical Education Center by providing
fieldwork for clinical training. It also offers clinicalservices to patients with various development problems and places an emphasis on research to provide
evidence-based clinical and educational activities.

In the year 2006, the Department of Child Psychiatry consisted of 10 psychiatrists including 3 full-timechild psychiatrists and 10 psychologists (full-time andpart-time). Although patients with various disorders
are seen, the focus of the department is mainly on patients with developmental disorders. We offer services
to patients with a broad range of developmental disorders including Pervasive Developmental Disorders(PDD), Attention-Deficit/Hyperactivity Disorder(AD/HD), Learning Disabilities (LD), Mental Retardation (MR), tic disorders and child Obsessive-Compulsive Disorders (OCD).
The number of new patients in the year 2006 wasmore than 470, in contrast to 300 in the year of 2005.
This indicates an increase of about 50% comparedwith that of the previous year. Among the new patients,
45% were patients with disorders of psychologicaldevelopment including LD, with PDD being the mostprevalent diagnosis. The second most prevalent diagnosis was tic disorders (15%), followed by AD/HD(10%) and stress-related disorders (10%). The agegroup of these patients was distributed widely fromearly infancy to adulthood, and the largest number ofpatients being those in the late infancy to early childhood group. Among follow-up patients, disorders of
psychological development were again the most pre-

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valent at 45%, followed by tic disorders, stress-relateddisorders, AD/HD and mood disorders. About half ofthe patients at follow-up were adult patients, especially high in number were patients in their twenties,
constituting a total of 20%. This highlights the needfor long-term follow-up in patients with developmental disabilities.
Clinical activities are largely divided into two areasof general child psychiatry outpatient services andinterventions for children with developmental disabilities.
Services for the general child psychiatry outpatientsare provided by psychiatrists in the areas of pharmacotherapy, psychotherapy, psychoeducation and also
work closely with the schools and community.
Interventions for developmentally disabled children
consist of “developmental psychology outpatient services” and “short-term group therapy”. Patients involved in interventions are children with developmental disabilities, and individualized cognitive developmental therapy is planned for each child. “Developmental psychology outpatient clinic” provides
services in the following areas: (1) evaluation of cognitive and behavioral development, (2) individual
treatment of the child (3) counseling of parents andproviding information to the child’s support network(relatives, schools). “Short-term group therapy” is a
10 session group therapy for a small group of children
with similar developmental levels. These services areprovided mainly by psychologists under the supervision of child psychiatrists.

Education
As part of the Clinical Education Center of Mental
Development, two training courses (Course A and B)
are offered for graduate level students and various
mental health professionals including psychiatrists
and pediatricians. Course A is a lecture course which
incorporates an interactive component with role-playexercises and case conferences. Course B is an intensive training course, which includes more clinical experience through participation in intervention andpsychological assessment.
Course A is composed of 11 sessions of 3 hour lectures and is offered twice a year, with a total of approximately 140 trainees per year. Trainees consistedof a wide range of professionals, including those in
the medical field, such as physicians, psychologists,
educators and social workers. This mixture of a variety of professions laid the groundwork for creating a
multidisciplinary network for professionals involved
in issues related to mental development. Feedback
from questionnaires indicated that 80% of the trainees
found the course useful.
Course B is offered for a duration of 6 months, with
3 days per week of clinical training. Trainees haveincluded psychiatrists and pediatricians.
A seminar and symposium is held annually in orderto facilitate understanding of mental development anddevelopmental disorders among the general public. In
the year 2006, a seminar entitled “Developmental disorders and society” and a symposium entitled “Intervention for developmental disorders” each attracted an
audience of about 200 and 600 people respectively.
Undergraduates and psychiatry residents from the
University of Tokyo have opportunities to observe
evaluations and outpatients services as part of theircourse. They are also required to actively participate
in “short-term group therapy”.

Research
We participate in investigation of etiology and development of effective treatment on PDD and AD/HD,
which are organized in collaboration with the Department of Neuropsychiatry and other research, educational and clinical facilities. In addition, research
related specifically to the clinical activities in the Department of Child Psychiatry is currently being investigated.
Clinical evaluation and treatment
The reexamination of reliability and validity of Ohta Staging (an evaluation system using symbol development for cognitive developmental therapy developed in the former child division of the Department of
Neuropsychiatry) and investigation of the effectiveness of present interventions for children with PDD
are being conducted.
A comparison study of the effectiveness of individual treatment and “short-term group therapy” in arandomized control study is being undertaken.
In another study, the possible relations among clin-

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ical characteristics such as tics and obsessivecompulsive symptoms in Tourette syndrome (chronictic disorder with multiple motor tics and one or more
vocal tics) and child OCD are being evaluated.
Neuropsychological research
Neuropsychological data on PDD, AD/HD andTourette syndrome are being collected. Analysis of therelations among neuropsychological findings and theclinical evaluation as well as comparisons between
patients and their healthy siblings are being conducted.
Genetic research
Research exploring susceptibility genes of PDD inchromosome 2, long arm of chromosome 7 and longarm of chromosome 15 are conducted. As we are interested in gene-environment interaction, we are examining influence of endocrinologic change including
thyroid hormone in PDD. In addition to the molecular
genetic study, investigation of specific family and environment of Tourette syndrome is being undertaken.
Neuroimaging
Studies include structural MRI, MEG and NearInfrared Spectroscopy (NIRS) and exploration of thepathogenesis of developmental disorders such as PDD.
The main focus is the examination of prefrontal bloodflow in PDD and Tourette syndrome by NIRS which is
non invasive and easily applicable to children and developmentally disabled individuals.

References
1. Ohta M, Kano Y, Nagai Y. Catatonia in individuals with autism spectrum disorders in adolescenceand early adulthood: A long-term prospective
study. Int Rev Neurobiol 2006; 72: 41-54.
2. Rosario-Campos MC, Miguel EC, Quatrano S,
Chacon P, Ferrao Y, Findley D, Katsovich L, Scahill L, King RA, Woody SR, Tolin D, Hollander E,
Kano Y, Leckman JF. The Dimensional
Yale-Brown Obsessive-Compulsive Scale (DYBOCS): An instrument for assessing obsessivecompulsive symptom dimensions. Mol Psychiatry
2006; 11: 495-504.
3. Inoko K, Nishizono-Maher A, Tani S, Kano Y,

Kishimoto J, Hayakawa N, Honjo S, Kasahara M,
Saito K, Ishii K, Osawa M: Reliability and validity of a Japanese version of the Yale Global Tic
Severity Scale: A preliminary study. Jpn J Child
Adolesc Psychiatr, 47(Supplement) 2006; 38-48.
4. Koishi S, Yamamoto K, Matsumoto H, Koishi S,
Enseki Y, Oya A, Asakura A, Aoki Y, Atsumi M,
Iga T, Inomata J, Inoko H, Sasaki T, Nanba E,
Kato N, Ishii T, Yamazaki K. Serotonin transporter gene promotor polymorphism and autism: afamily-based genetic association study in Japanese population. Brain Dev 2006; 28: 257-60.
5. Sadamatsu M, Nanai H, Xu X, Liu Y, Kato N. A
review of animal models for autism: implicationof thyroid hormone. Congenit Anom (Kyoto)
2006; 46: 1-9.
6. Kuwabara H, Kasai K, Takizawa R, Kawakubo Y,
Yamasue H, Rogers MA, Ishijima M, Watanabe K,
Kato N. Decreased prefrontal activation during
letter fluency task in adults with pervasive developmental disorders: a near-infrared spectroscopy
study. Behav Brain Res. 2006, 172: 272-77.

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Clinical Genomics
Director & Professor
Shoji Tsuji, M.D., Ph.D.

Vice-director & Lecturer
Jun Goto, M.D., Ph.D.

Homepage
Organization
The Department of Clinical Genomics started as a
special unit conducting genomic medicine or clinicalhuman genetics services in 2003. Our department
functions as the core unit to accomplish an appropriate
and efficient application of results of recently advanced human genetics and genomics to clinical practice in the hospital and as the unit of training andeducating specialists of human genetics practice. It
consists of one professor and many different specialties participate in the department. They include pediatricians, obstetricians, internist (cardiologists, diabetologists, an endoclinologist, and neurologists), adermatologist, a staff of the department of clinicallaboratory medicine and faculty members of the Departments of Human Genetics and Nursing Science.

Activities
The exclusive consultation room (Room 200) is allocated in the outpatient clinic. Consultation andcounseling is performed by a team of medical doctor
and non-M.D. staffs. All cases are reviewed and discussed at the conference which is held on the 1st
Monday every month.
Counseling of participants in researches including
genome or gene analysis is a duty with which the hospital and the faculty charge the department.
To build suitable clinical systems including modern
genomic medicine we are cooperating with other departments. We are participating in Marfan’s Syndrome
Clinic which is managed collaboratively by the De-partments of Cardiovascular Surgery, Cardiovascular
Medicine, Pediatrics, Spinal Surgery and Ophthalmology. We are also collaborating with Clinical Laboratory Center, Pharmaceutical Services, Departments of Planning Information and Management,
Gastroenterology, Cardiovascular Medicine and Neurology and started a clinical pharmacogenetics service
for proton pump inhibitors and warfarin in 2006.

References
1. Saito Y, Matsumura K, Shimizu S, Ichikawa Y,
Ochiai K, Goto J, Tsuji S, Shimizu T. Pigmentary
macular dystrophy in spinocerebellar ataxia type 1.
J Neurol Neurosurg Psychiatry 2006;77(11):1293.
2. Sakai K, Yamada M, Sato T, Yamada M, Tsuji S,
Takahashi H. Neuronal atrophy and synaptic alteration in a mouse model of dentatorubralpallidoluysian atrophy. Brain 2006;129:2353-62.
3. Hattori N, komine M, Kaneko T, Shimizu S, Tsunemi Y, Koizumi M, Goto J, Hashimoto T. A caseof epidermolysis bullosa simplex with a newly
found missense mutation and polymorphism in thehighly conserved helix termination motif among
type I keratins, which was previously reported asa pathogenic missense mutation. Br J Dermatol
2006;2006:1062-1063
4. Shimohata, T, Hara, K, Sanpei, K, Nunomura, J,
Maeda, T, Kawachi, I, Kanazawa, M, Kasuga, K,
Miyashita, A, Kuwano, R, Hirota, K, Tsuji, S,
Onodera, O, Nishizawa, M. and Honma, Y. Novellocus for benign hereditary chorea with adult onset maps to chromosome 8q21.3- q23.3 Brain

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130:2302-2309, 2007
5. Hara, K., Momose, Y., Tokiguchi, S., Shimohata,M., Terajima, K., Onodera, O., Kakita, A., Yamada, M., Takahashi, H., Hirasawa, M., Mizuno,
Y., Ogata, K., Goto, J., Kanazawa, K., Nishizawa,M., and Tsuji, S. Multiplex families with multiple
system atrophy. Arch Neurol. 64:545-51, 2007
6. Sawada H, Ishiguro H, Nishii K, Yamada K, Tsuchida K, Takahashi H, Goto J, Kanazawa I, Nagatsu Tspecific huntingtin aggregates in humanhuntingtin knock-in mice. Neurosci Res 2007;57:559-573.
7. Tsuji S, Onodera O, Goto J, Nishizawa M. Sporadic ataxia in Japan – a population-based epidemiological study. Cerebellum 2007 (in press).

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Cooperative Unit of Medicine andEngineering Research
Organization
The University of Tokyo Hospital
Cardiovascular Medicine, Nutrition and Metabolism, Surgical Oncology, Vascular Surgery,
Artificial Organ and Transplantation, Cardiac Surgery, Thoracic Surgery, Neurosurgery,
Urology, Orthopaedic Surgery, Oral and maxillofacial Surgery, Radiology, Tissue
Engineering Unit, Department of Clinical Bioinformatics, Clinical Vascular Regeneration,
Bone & Cartilage Regenerative Medicine, Cartilage of Bone Regeneration, Department of
Immunotherapeutics (Medinet)

Engineering and Pharmaceutical Research
Chemical System Engineering, Mechanical Engineering, Quantum Engineering and
System Science, Nuclear Engineering and Management, Chemistry and Biotechnology,
Material Engineering, Information Science and Technology, Frontier Sciences,
Pharmaceutical Sciences Laboratory of Chemistry and Biology, Center for Disease
Biology and Integrative Medicine, Center for Disease Biology and Integrative Medicine
Biomedical Materials and Systems, Center for Disease Biology and Integrative Medicine
Clinical Biotechnology, Research Center for Advanced Science and Technology, Instituteof Industrial Science

Homepage

http://plaza.umin.ac.jp/~ikourenk/

Introduction and Organization
The application of an advanced bioscience to a newtechnical development of clinical medicine has become an important subject for research in the 21st
century. We’ve established Cooperative Unit of Medicine and Engineering Research at The University ofTokyo Hospital to create a new research and education
center, which cross-sectionally unites medicine withengineering research for the development of a next
generation medical technology.
2002 June. The establishment of Cooperative Unitof Medicine and Engineering Research was approvedby a hospital administration committee as a special
practice unit that belongs to The University of Tokyo
Hospital.
2002 September. A steering committee of Cooperative Unit of Medicine and Engineering Research wasorganized by representative members of relevant clin-

ical departments. The committee made a decision of
the following basic principles; recruitment for the participation to this unit should be, as a general rule, an
open call for a joint project of clinical department andengineering or pharmaceutical research group in The
University of Tokyo, an equipment/administration
expense of a laboratory should be a responsibility of
the user, and a basic participation period to this unit
should be three years and for the continued participation in the unit, a review and approve of the steeringcommittee is indispensable.
2002 October. An open call for participants to thisunit started. There were 18 applications and the steering committee approved all projects after review. A
liaison conference of Cooperative Unit of Medicine
and Engineering Research was organized by a representative member of each project. Configuration ofeach project in a space of 554.4m2 that is consisted ofa portion of the first floor and the basement of an administration building came to a decision by the con-

367

ference.
2003 May. The construction of Cooperative Unit ofMedicine and Engineering Research was completed.
The cost of the construction was shared by the participation groups.
2003 May 22. The first research meeting of Cooperative Unit of Medicine and Engineering Research
took place and research activities started.
2004 September 3. The second research meeting of
Cooperative Unit of Medicine and Engineering Research took place.
2005 September 13. The third research meeting of
Cooperative Unit of Medicine and Engineering Research took place.
2006 December 21. The fourth research meeting of
Cooperative Unit of Medicine and Engineering Research took place.
2007 December 13. The fifth research meeting of
Cooperative Unit of Medicine and Engineering Research will take place.

Research activities
Development of Advanced Sterotactic Rediation
Cancer Rherapy System
Department of Radiation Oncology
Nuclear Engineering Research Laboratory
Department of Chemical System Engineering
High Precision Stereotactic X-ray Cancer Theraoy
System. Development of Advanced Compact Electron
Linear Accelerator for Cancer Inspection and Therapy
Laboratory of Nano-crystals in Oncology
Department of Chemical System Engineering
Department of Surgical Oncology
To develop an exact diagnosis and treatment system
for the micro-metastasis of neoplasm by using nano-crystal particles, and to introduce it to clinical use.
To visualize peritoneum metastases (peritonitis) andmicro-metastasis of neoplasm which cannot bechecked in naked eye, and apply it to an operation or
the determination of a medical treatment plan. To
search for the new method for treating neoplasm byusing biological changes of the cells after up taking
nano-crystal particles.
Laboratory of Medical Ultrasound with Micro-

bubbles in Oncology
Department of Mechanical Engineering, Fluids Engineering Laboratory
Department of Surgical Oncology
To develop easy, precise, non-invasive systems to treat
human disease. To devise a method to induce microbubbles effectively to treat human tumors in deep situ.
To make a precise assessment on tumor invasion inμm order by injecting microbubbles into tumor arteries. To develop a non-invasive treatment system using
HIFU devise and microbubble contrast agents.
Medico-engineering Laboratory for Microsurgical
Robotics and Virtual Simulation Laboratory (MRVLabo)
Laboratories of A Morita, Neurosurgery
Dept. Engineering Synthesis, M Mitsuishi
To develop Microsurgical robotic system and 3D visual system for telesurgery
Laboratory of Cavitation & Lithotripsy
Department of Urology, Faculty of Medicine
Department of Mechanical Engineering, School ofEngineering
Development of a new method of lithotripsy using
high intensity focused ultrasound induced cavitation.
Department of Clinical Bioinformatics
Department of Clinical Bioinformatics
Chemical System Engineering
Our specific targets include clinical support information systems (e.g.: electronic medical records andnursing support information systems) to support clinical practice with knowledge gained from genomic
information; clinical testing information systems to
support genome-based drug development and translational research; database systems to integrate disease
and genomic information; and information management systems of genome and clinical information.
Surgical Robot System Lab.
Robotics, Dynamics, and Control Laboratory
Department of Mechano-Informatics
University of Tokyo
To develop: robot systems for endoscopic cardiac
surgery, small-occupancy endoscopic robots, virtual
stillness technology for cardiac surgery, and highly368

reliable surgical robot systems
Vascular Biomebical Engineering Laboratory
Department of Vascular Surgery
Department of Tissue Engineering, The University ofTokyo Hospital
Medical Precision Engineering Laboratory, Instituteof Environmental Studies, The University of Tokyo
Development of minimally invasive diagnostic andtherapeutic technologies for vascular surgery throughcollaboration research.
Orthopedic clinical biomechanics laboratory
The Department of Orthopaedic Surgery, The University of Tokyo.
Graduate School of Information Science and Technology, The University of Tokyo.
To develop a non-invasive method for predicting bonestrength. To develop osteosynthetic devices.
Minimally invasive cardiac surgery with the integral videography system
Department of Cardiothoracic Surgery, Graduate
School of Medicine, University of Tokyo
Advanced Therapeutic and Rehabilitation Engineering
Laboratory, Department of Mechano-Informatics,
Graduate School of Information Science and Technology, University of Tokyo
To develop: real-time three-dimensional echocardiography, suture device with liner probe, integral
videography, and minimal invasive cardiac surgery
monitored by real-time three-dimensional echocardiography without cardiopulmonary bypass
Division of Neutron Capture Therapy & Immunotherapy for Cancer
Department of Cardiothoratic Surgery, Graduate /School of Medicine
Department of Radiology, University of Tokyo Hospital
Department of Quantum Engineering and System Science, School of Engineering
Department of Nuclear Engineering and Management,
School of Engineering
Research Center for Advanced Science & Technology
Endowment Department, Department of Immunotherapeutics (Medinet)

In order to control and eliminate human cancers, wedevelop the neutron capture therapy (BNCT) using
small neutron accerelator equipped to hospital andalso develp more effective immumotherapeutic approaches.
Molecular Imaging Laboratory, Cooperative Unitof Medicine, Engineering and Pharmaceutical Reserch
Tetsuo Nagano, Laboratory of Chemistry and Biology,
Graduate School of Pharmaceutical Sciences
Yasunobu Hirata, Department of Cardiovascular
Medicine
To develop chemical probes for imaging of biomolecules To elucidate mechanisms and to establish
cures of arteriosclerosis
Laboratory of Artificial Organs
Division of Artificial Organs & Transplantation: Katsutoshi Naruse and Lei Guo
Institute of Industrial Science and Center for Disease
Biology and Integrative Medicine, Graduate School of
Medicine: Yasuyuki Sakai
Laboratory of Artificial Organs consists of researchers
belonging to Division of Artificial Organs & Transplantation, and Sakai Laboratory. We have been collaborating in the research of bioartificial liver support
systems in the past 10 years. Our current specialization is, development of artificial liver support, clinicaluse of new apheresis therapy, development of transgenic pig producing human serum albumin, and development of implantable liver tissue equivalents.
Laboratory of Applied Metabolic Biotechnology
Department of Cardiovascular Medicine, Graduate
School of Medicine
Department of Metabolic Diseases, Graduate Schoolof Medicine
Department of Chemistry and Biotechnology, Schoolof Engineering
To establish the system and methods for engineering
the novel model mice of life style-related diseases
using RNAi technology and biotechnology. To elucidate the mechanisms by which adipose tissue derived
factors, adipokines, contribute to the development of
the metabolic syndrome. To explore the signal transduction pathways of major adipokines including adi-369

ponectin
Laboratory of Biomaterial Science
Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo
Ishihara & Takai Lab, Department of Materials Science, Graduate School of Engineering, The Universityof Tokyo
Division of Biomedical Materials and Systems, Center
for Disease Biology and Integrative Medicine, Facultyof Medicine, The University of Tokyo
Department of Oral and Maxillofacial Surgery, Faculty of Medicine, The University of Tokyo
Inhibition of aseptic loosening of artificial joints bynano-grafting of a novel biocompatible polymer MPC.
Creation of biocompatible biomaterials optimized forbone, cartilage and vascular regeneration. Regeneration of bone and cartilage tissue in vitro promoted byphysical stimulation
Molecular and cellular physiology, Computational
mechanics
Department of Cardiothoracic Surgery, The Universityof Tokyo Hospital
Biomechanics Laboratory, Graduate School of Frontier Sciences, The University of Tokyo
Inhibition of aseptic loosening of artificial joints bynano-grafting of a Objectives and Research Fields.
Development of multi-scale, multi-physics heart simulator and its clinical application. Molecular andcellular physiology, Computational mechanics.
Laboratory of Hard-Tissue Nanomedicine
Kataoka & Yamasaki Lab, Department of Materials
Science, Graduate School of Engineering, The University of Tokyo
Department of ″Menicon″ Cartilage & Bone Regeneration, Graduate School of Medicine, The Universityof Tokyo
Department of Bone & Cartilage Regenerative Medicine, Graduate School of Medicine, The University ofTokyo
Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo Department of Oral andMaxillofacial Surgery, Faculty of Medicine, The University of Tokyo
Division of Clinical Biotechnology, Center for Disease

Biology and Integrative
Medicine, Graduate School of Medicine, The University of Tokyo
Division of Tissue Engineering, The University of Tokyo Hospital
Development of a non-viral gene delivery system bysupramolecular nanotechnology. Development of anon-viral siRNA delivery system by supramolecular
nanotechnology. Production of regenerated cartilage
and bone with high safety and usefulness . Establishment of practical production and quality control systems. Promotion of the clinical application of regenerated cartilage and bone. Development of easy, precise, non-invasive systems to detect osteoblastic andchondroocytic differentiation. Determination of a finite set of signaling factors sufficient for induction of
osteoblasts and chondrocytes. Development of amethod to induce osteogenesis and angiogenesis simultaneously . Development of a cell-sheet culture
system for bone and cartilage. Screening for compounds that induce bone and cartilage regeneration
Cooperative Unit of Kataoka Laboratory and Department of Vascular Regeneration
Department of Vascular Regeneration, Division of
Tissue Engineering, The University of Tokyo Hospital
Kataoka Laboratory, Department of Materials Scienceand Engineering, Graduate School of Engineering,
The University of Tokyo
To achieve effective and safe in vivo gene therapy ofcardiovascular and vascular diseases, we are developing non-viral gene vectors based on nano-scaled polymer assemblies (polymeric micelles). Polymeric
micelles, which are spontaneously formed from block
copolymers, have a core containing packaged genes
surrounded by biocompatible poly(ethylene glycol)(PEG) palisades, and a variety of pilot molecules canbe installed on the surface of polymeric micelles. This"virusmimicking" nanoparticles might achieve efficient gene transfer to the targeted tissues or cells because of protection of the loaded DNA from nucleaseattack, their lowered non-specific interaction withproteins and cells and facilitated internalization by thetargeted cells through specific interaction of the pilot
molecules. Currently, our research has been focusedon in vivo gene transfer to artery walls and muscles
using polymeric micelles incorporated genes.

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22. Miyahara T, Koyama H, Miyata T, Shigematsu H,
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M, Akagi D, Hosaka A, Miyahara T, Ishii S, Kimura H, Deguchi J, Shigematsu K, Shigematsu H
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26. Nagata D, Takahashi M, Sawai K, Tagami T, Usui
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27. Takeda R, Nishimatsu H, Suzuki E, Satonaka H,
Nagata D, Oba S, Sata M, Takahashi M, Yamamoto Y, Terauchi Y, Kadowaki T, Kangawa K,
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30. N. Herlambang, H. Liao, K. Matsumiya, K. Masamune, H. Tsukihara, S. Takamoto, et. al. Mitralvalve movement visualization using real-time
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and Surgery, vol. 1, Suppl. 1, p.218-220, 2006.

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Department of Pharmacy
Professor
Hiroshi Suzuki, Ph.D.

Associate Professor
Kousei Ito, Ph.D.

Assistant Professor
Akihiro Hisaka, Ph.D.

Associate
Yoshitsugu Yanagihara, Ph.D.,
Kazuo Takayama,
Nobuhiro Yasuno Ph.D.

Homepage

Tomonobu Uchino, Ph.D.,
Takehito Yamamoto,

Tappei Takada, Ph.D.,
Masashi Honma,

http://square.umin.ac.jp/todaiyak/index.html

Introduction and Organization
We have eleven faculty members, 47 pharmacy
staffs, 23 pharmacy residents, and 9 graduate students
and 5 undergraduate students from the faculty ofpharmaceutical sciences (fiscal year 2006).

Clinical activities
Department of Pharmacy consists of the following
six sections:1) Drug information and research section
This section offers drug information for questions
from the medical person, executes and supports
the medicine management to inpatients. In addition, the section prepares materials for pharmaceutical affair committee, where each medicine isdiscussed whether it should be adopted or deleted.
Preparation of several periodicals regarding drug
information for clinicians is also included.
2) The dispensing section
After inspecting all prescriptions for contraindications or improper use, medications are dispensed.
Drug information is given to outpatients from thissection, using a private room if necessary. The
computerized order system is linked with auto-

matic packaging machines for oral medicines, bar
code label printer, and automatic dispensing system for injection drugs.
3) Pharmaceutical section
This section sterilizes formulations of a pharmaceutical such as injection medicines, instillation
medicines and decontaminating chemicals. They
prepare capsule medicines, ointment medicines,
suppositories, central vein nutrition (IVH) for inpatients and in-home care patients. After strict
inspection of prescriptions, they also dispenseanti- malignant tumor medicine (database is constructed based on the submitted protocols and thepatient information). They also do mixing of injections at each staff station of ICU, CCU, HCU(both the surgical department and internal department), internal medicines for hematology andoncology. In order to support advanced medicalcare, they develop and check formulations (characterization of the uniformity, stability and so on)of the medicine which is quite necessary for certain patients, but is not marketed.
4) Drug matters and drug management section
Drug matter section manages the adoption of
medical supplies (in-hospital and out-hospital),
periodically reconsiders the adopted medicines,

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and also manages the accountings of all the medicines and other materials used in our department.
This section also takes statistics of every information of drug affairs. Drug management section
takes care of supplying and safekeeping of all the
in-hospital medicines (approx. 2,150 items), outpatient medicines, anesthetics, muscle relaxation
drugs, psychotropic drugs, poison medicines.
5) Nacrotic section
Under the supervision of authorized manager fornarcotics (the director of the pharmacy department), narcotics are properly managed, recorded,
reported, inspected and directed. Nacrotics areproperly arranged and managed at the dispensing
section and each medical care section.
6) Ward section
They contribute to the team medical care by providing specialized drug information and sharing
them with all the staffs involved in the treatment.
① Investigation of carrying medicines and the side
effect histories, allergy histories etc. at the timeof hospitalization② Procurement and appraisal of patient’s basic
information about the disease, compilation of
the medicine history③ Participation for conferences④ Arrangement and mixing of injections for eachpatient⑤ Monitoring of medication guidance and the side
effect for the patient, and compilation of guidance record⑥ Offering the doctor with drug information, prescription design support and detailed contentsof medication guidance to each patient⑦ Investigation and management of ward stock
medicine. We extended these activities to 12
floors and 17 diagnosis and treatment courses
Statistical Data (fiscal year 2006)
Number of items on in-hospital formulary:
approx. 2,170
Number of prescriptions filled (annual)out-patients:
479,589(outside:
407,032)(inside:67,175)(chemotherapy:
5,378*)*: estimated from later half of 2006th

in-patients:
410,027(oral and external:
193,421)(injection drugs:
191,232)(IVH:
19,638)(chemotherapy:
5,736)
TDM consultations (annual):
18,263
Numbers of hospital pharmaceutical cares (annual):
3,533

Educational Activities
The department of pharmacy takes various responsibilities of education with regard to clinical pharmacy,
pharmacology, and pharmacokinetics for students andgraduate students in the faculty of medicine, in thefaculty of pharmacy, and in the school of health sciences and nursing. We also have our own one-year
post-graduate training course optimized for new pharmacists.
For students in the faculty of medicine, we are in
charge of "Pathogenetic and Pathology" as an optionalcourse lecture. We are providing a free quarter practice course for some M1 and M2 students for 2 weeks
and teach basic molecular and biochemical techniques
as well as the pharmacokinetic theory to them. We areproviding a 3-days practice course as a part of compulsory clinical practice for the M3 and M4 students
and teach clinical pharmaceutics and practical knowledge of prescription and risk management to them.
For the students in the health sciences and nursing, weare in charge of clinical pharmacokinetics lectures as apart of a compulsory subject, "Pharmacology and
Toxicology".
For students in the faculty of pharmacy, we are in
charge of two series of lectures for the undergraduate
students: "Clinical Pharmacy I" (compulsory subject)and "Clinical Pharmacy II" (an optional course). They
are educated for the clinical pharmacology and pharmacokinetics. For the graduate students, we are in
charge of "Advanced Course of Medical Pharmacy"(every other year) as a cooperator of the ClinicalPharmacokinetic. Recent trends of the medical pharmacy as well as the practical developments and future
visions of the department of pharmacy are presented
in this lecture. We are responsible for the hospital
practice courses (10 days in total) and teach practicaltechniques of pharmacists such as drug preparations

378

and patient consultation. In addition to these, we educate 4th year students and graduate students who
moved to the Clinical Pharmacokinetics.
In 2006, 23 pharmacists completed our one-year
post-graduate training course. They learned various
practical knowledge and techniques necessary for hospital pharmacists. This course takes a role of 6-years
education of the faculty of pharmacy in advancewhich will start 2 years later. In addition, we are promoting life-long education of pharmacists in the local
area by holding monthly regular technical workshop.

Research activities
A proper medication requires scientific evidences.
However, it is not fully understood that what the target
for main and side-effect of the drug is, as well as the
enzymes and transporters involved in the dispositionof drugs. Moreover, a number of patients are waitingfor development of new pharmacotherapy. We aretrying to clarify basic mechanisms of the genetic or
acquired diseases to develop useful pharmacotherapy
for an individual patient. Our research fields include
the regulation of the expression and function oftransporters related to the pharmacotherapy, polymorphism of drug metabolizing enzymes and transporters governing the drug disposition, and drug information research.
Followings are the topics of our recent research:
1) Regulation of transcription and function of transporters in the liver and intestine involved in cholesterol homeostasis.
2) Intracellular trafficking and dynamic rearrangementof transporter complexes.
3) Regulation of intracellular trafficking and transcription of signaling molecules involved in bonehomeostasis
4) Polymorphism of drug metabolizing enzymes andtransporters. Quantitative prediction of clinical effects.
5) Clinical data analysis and utilization of drug package insert, information on drug-drug interaction,and patient data for the development of safer andbetter medications for patients.

References
1. Kusama M, Kubota T, Matsukura Y, Matsuno K,
Ogawa S, Kanda Y, Iga T., Influence of glutathione S-transferase A1 polymorphism on thepharmacokinetics of busulfan. Clin Chim Acta.
368(1-2):93-8. (2006).
2. Mita S, Suzuki H, Akita H, Hayashi H, Onuki R,
Hofmann AF, Sugiyama Y., Vectorial transport ofunconjugated and conjugated bile salts by monolayers of LLC-PK1 cells doubly transfected withhuman NTCP and BSEP or with rat Ntcp and Bsep.
Am J Physiol Gastrointest Liver Physiol. 290(3):G550-6. (2006).
3. Horie T, Li T, Ito K, Sumi S, Fuwa T., Aged garlic
extract protects against methotrexate-induced
apoptotic cell injury of IEC-6 cells. J Nutr. 136(3Suppl):861S-863S. (2006).
4. Ohno Y, Kusama M, Hisaka A, Yanagihara Y, Suzuki H., Analysis of pharmacokinetic data provided in Japanese package inserts and interview
forms focusing on urinary excretion of pharmacologically active species. Yakugaku Zasshi. 126(7):489-94. (2006).
5. Sakamoto S, Suzuki H, Kusuhara H, Sugiyama Y.,
Efflux mechanism of taurocholate across the rat
intestinal basolateral membrane. Mol Pharm. 3(3):275-81. (2006).
6. Sekine S, Ito K, Horie T., Oxidative stress andMrp2 internalization. Free Radic Biol Med. 40(12):2166-74. (2006).
7. Ohtake E, Kakihara F, Matsumoto N, Ozawa S,
Ohno Y, Hasegawa S, Suzuki H, Kubota T., Frequency distribution of phenol sulfotransferase
1A1 activity in platelet cells from healthy Japanese subjects. Eur J Pharm Sci. 28(4):272-7.
(2006).
8. Okiyoneda T, Kono T, Niibori A, Harada K, Kusuhara H, Takada T, Shuto T, Suico MA, Sugiyama Y, Kai H. Calreticulin facilitates the cellsurface expression of ABCG5/G8. Biochem Biophys Res Commun. 347(1):67-75. (2006).
9. Mita S, Suzuki H, Akita H, Hayashi H, Onuki R,
Hofmann AF, Sugiyama Y., Inhibition of bile acidtransport across Na+/taurocholate cotransporting
polypeptide (SLC10A1) and bile salt export pump
(ABCB11)-coexpressing LLC-PK1 cells by cho-

379

lestasis-inducing drugs. Drug Metab Dispos. 34(9):1575-81. (2006).
10. Okiyoneda T, Niibori A, Harada K, Kohno T, Hashimoto Y, Kusuhara H, Takada T, Shuto T, Suico
MA, Sugiyama Y, Kai H., Bafilomycin
A1-sensitive pathway is required for the maturation of cystic fibrosis transmembrane conductanceregulator. Biochim Biophys Acta. 1763(10):101723. (2006).
11. Ninomiya M, Ito K, Hiramatsu R, Horie T., Functional analysis of mouse and monkey multidrug
resistance-associated protein 2 (Mrp2). Drug Metab Dispos. 34(12):2056-63. (2006).

382

Division of
Basic Medical Sciences（Ⅰ）
Professor
Toru Miyazaki, M.D.,Ph.D.

Lecturer/Associate Professor
Satoko Arai, Ph.D.

Endowment Lecturer
Sei-ichi Yusa, Ph.D.

Research Fellow
Miwako Kitazume, Ph.D.

Homepage

http: //tmlab.m.u-tokyo.ac.jp/

Research
Our laboratory will focus on clarification of thepathogenesis of various diseases and the related
physiological machineries in cellular and molecular
aspects. Based on our technical advantage in genemanipulation via gene knockout and transgenesis, wewill give high priorities to in vivo analyses. This willdefinitively contribute to the direct therapeutic application of our findings. Since our rationale is to challenge to uncharacterized disease mechanisms andphysiologies, we will not restrict our interest, strategy
or technique employed, in certain specific field.
Rather, we will expand our research area by establishing different collaborations with a broad spectrumof investigators. We believe this fits to the policy of
the CDBIM, which aims the development of a comprehensive science including the fundamental andclinical medicines, and the biotechnology. Overall, we
will attempt to discover novel biological insights
rather than to study details of previously characterized
physiologies, by targeting molecules newly identified
by ourselves. The major specific aims during the next
five years are as follows:

1. Role of Apoptosis Inhibitor expressed byMacrophages (AIM) in atherosclerosis development.
AIM, which we initially identified as a soluble
apoptosis inhibitory factor, is largely produced by tissue macrophages. Recently, we found that AIM expression induction is highly correlated to hyperlipidemia; and that expression of AIM is critical in progression of atherosclerosis as assessed in AIM
knockout mice. We will isolate the putative receptor
for AIM, and elucidate the entire signaling pathway of
how AIM inhibits apoptosis. In addition, by generating functional antibodies against human AIM, we willdevelop a potential treatment of atherosclerosis by
suppressing AIM activity in the body.
2. Epigenetical regulation of Genome-Stability via
Polycomb and its relevance to oncogenesis.
Recently, we discovered a novel Polycomb groupprotein MBT-1, which specifically dictates the maturational transition of immature myeloid progenitor
cells. We will clarify the definitive molecular mechanism of how MBT-1 regulates the myelopoiesis, which
may open avenues for the further understanding of themechanisms responsible for leukemogenesis. In addition, we will perform a large scale screening of leukemia patients for the mutation and/or the transloca-

383

tion of the MBT-1 gene (locus).
3. Regulation of mitosis progression by DEDD and
its influence on cell & body sizing and oncogenesis.
It has been suggested that the regulation of apoptosis is crucially involved in tumor development. Our
recent analysis of knockout mice of the death effector
domain (DED) containing element DEDD-1 has implied an important role of DEDD-1 in tumor progression. We will further determine the involvement of
DEDD-1 in tumorgenesis in the context of apoptosis
as well as of other potential machineries. We will also
study the function of a similar molecule DEDD-2 bothin vivo and in vitro. These studies will not only provide a novel insight into the influence of apoptosis intumorgenesis, but also suggest a potentiality of tumor
manipulation by modulating expression of DEDD
molecules.
4. Analysis of pathogenesis for IDDM via gene targeting in NOD-derived ES cells.
Insulin dependent diabetes mellitus (IDDM) is an
autoimmune disease that is characterized by the specific destruction of the insulin-producing β-cells of
the Langerhans islets within the pancreas. An important animal model for IDDM is the non-obese diabetic(NOD) mouse. Since humans and the NOD mouseshare most of the fundamental characteristics of
IDDM, the NOD mouse has been extensively studied
in order to better understand the etiology and pathogenesis of the disease. To date, more than twenty insulin-dependent diabetes (Idd) genes that influence thedisease have been mapped in the NOD mouse. In collaboration with Dr. Nagafuchi in Kyushu University,
we have established the experimental conditions thatprovide a high germline transmission efficiency ofNOD-derived ES cells, which enabled us to create
gene manipulated mice for specific diseaseresponsible genes on a pure NOD genetic background.
We will clarify the precise involvement of various Idd
genes in IDDM by targeting these genes in the
NOD-ES cells.
5. Towards the development of a definitive therapy for Propionic Acidemia.
Propionic acidemia (PA) is the most frequent inborn

error of organic acid metabolism in humans. It iscaused by a deficiency of propionyl-CoA carboxylase(PCC), which results in accumulation of toxic propionic acid, leading to furious acceleration of ketoacidosis. We generated a mouse model for the severe-type PA by disrupting the PCCA (α-subunit of
PCC) gene, and successfully rescued the mice bycomplementation of a partial PCC-activity restrictedly
in the liver or in the skin via a transgene. Having thisresult, we will establish a novel therapy for PA that isbased on an idea of developing “chimeric” organs via
transplantation of hepatic stem cells or fibroblast cells
into newborns or early infants.

Lab Activities
DBELS（Disease Biology Excellent Lecture Series）
We present a lecture series by top scientists in a variety of research fields related to disease biology. Sofar, eleven lecturers have been invited from many
places including Kyoto Univ., Hokkaido Univ., Riken
Institute, Tokyo Univ. of Science, Washington Univ.
(USA), Univ. of Basel (Switzerland).
DBELS-EXTRAAs a daughter series of DBELS, we started a technical lecture series for young scientists. We invite
various scientists from not only universities but also
research institutes or industries.
DBELS WORKSHOPThis summer (2007), we had a workshop at Unzen,
a great resort place in Nagasaki prefecture. Along thepolicy for DBELS, we invited 8 top-scientists from
Kyoto, Tokyo, Hokkaido, Okinawa, and Boston as
lecturers, and many young participants as audiences.
Staying in a beautiful resort hotel, we all had a scientifically and culturally fruitful time. The next workshop is scheduled to be held in Switzerland, probably
in2008 summer.
Music and ScienceAs an opening ceremony of our lab, we invited
Maestro Christian Zimerman (Pianist), for a concert
by him, and a discussion (with Prof. Miyazaki) on
Music and Science, at the Yasuda memorial auditorium (June 2006). More than 800 audiences have par-

384

ticipated.
Visiting Professors
In 2007, Prof. Edward K. Wakeland (Univ. of Texas
Southwestern Medical Center at Dallas) visited ourlab for 3 months, and had many activities. In 2008,
Profs. Diane Mathis and Christophe Benoist will join
our place.

Publications
1. Jayachandran, R., Sundaramurthy, V., Combaluzier, B., Korf, H., Huygen, K., Miyazaki, T.,
Albrecht, I., Massner, J. & Pieters, J. Survival of
Mycobacteria in macrophages is mediated byCoronin 1-dependent activation of calcineurin.
Cell 130: 1-14 (2007).
2. Miyazaki, T. & Arai, S. Two distinct controls of
mitotic Cdk1/cyclin B1 requisite for cell growthprior to cell division. Cell Cycle 6: 1419 - 1425
(2007).
3. Arai, S., Miyake, K., Voit, R., Nemoto, S., Wakeland, E.K., Grummt, I. & Miyazaki, T. The deatheffector domain containing protein DEDD is a
novel mitotic inhibitor requisite for cell growth.
Proc. Natl. Acad. Sci. USA 104: 2289-2294(2007).
4. Arai, S., Shelton, J.M., Chen, M., Bradley, M.N.,
Castrillo, A, Bookout, A.L., Mak, P.A., Edwards.
P.A., Mangelsdorf, D.J., Tontonoz, P. & Miyazaki,
T. A role of the apoptosis inhibitory factor
AIM/Spα/Api6 in atherosclerosis development.
Cell Metabolism 1: 201-213 (2005).
5. Arai, S. & Miyazaki, T. Impaired maturation of
myeloid progenitor cells exhibiting normal proliferative activity in mice lacking the novel Polycomb group protein MBT-1. EMBO J. 24: 18631873 (2005).
6. Haks, M.C., Lefebvre, J.M., Lauritsen, J.P.H.,
Carleton, M., Rhodes, M., Miyazaki, T., Kappes,
D.J. & Wiest, D.L. Attenuation of γδTCR signaling efficiently diverts thymocytes to the αβ lineage. Immunity 22: 595-606 (2005).
7. Kroll, J., Shi, X., Caprioli, A., Liu, H.H., Waskow,
C., Lin, K.M., Miyazaki, T., Rodewald, H.R. &Sato, T.N. The BTB-kelch protein, KLHL6, is involved in B-lymphocyte antigen receptor signal-

ing and germinal center formation. Mol. Cell.
Biol. 25: 8531-8540 (2005).
8. Arai, S., Minjares, C., Nagafuchi, S. & Miyazaki,
T. Improved experimental procedures for NODderived embryonic stem cells to achieve an efficient transmission into mouse germ line. Exp.
Diab. Res. 5: 219-226 (2004).
9. Kuwata, K., Watanabe, H., Jiang, S-Y., Yamamoto,T., Miyaji, C., Abo, T., Miyazaki, T. & Naito, M.
AIM inhibits apoptosis of T cells and NKT cells
in Corynebacterium-induced Granuloma formation in mice. Am. J. Pathol 162: 837-847 (2003).
10. Ito, Y., Arai, S., van Oers, N.S.C., Aifantis, I., vonBoehmer, H. & Miyazaki, T. Positive selection by
the pre-TCR yields mature CD8+ T cells. J. Immunol. 169: 4913-4919. (2002).
11. Miyazaki, T., Ohura, T., Kobayashi, M., Shigematsu, Y., Yamaguchi, S., Suzuki, Y., Hata, I.,
Aoki, Y., Yang, X., Minjares, C., Haruta, I., Uto,
H., Ito, Y. & Muller, U. Fatal propionic acidemia
in mice lacking propionyl-CoA carboxylase andits rescue by postnatal, liver-specific supplementation via a transgene. J. Biol. Chem. 276: 3599535999 (2001).
12. Haruta, I., Kato, Y., Hashimoto, E., Minjares, C.,
Kennedy, S., Uto, H., Yamauchi, K., Kobayashi,M., Yusa, S., Müller, U., Hayashi, N. & Miyazaki,
T. Association of AIM with hepatitis via supporting macrophage survival and enhancing phagocytotic function of macrophages. J. Biol. Chem.
276: 22910-2914 (2001).
13. Miyazaki, T., Hirokami, Y., Matsuhashi, N., Takatsuka, H. & Naito, M. Increased susceptibility ofthymocytes to apoptosis in mice lacking AIM, anovel murine macrophage-derived soluble factor
belonging to the scavenger receptor cysteine-richdomain superfamily. J. Exp. Med. 189:413-422(1999).
14. Miyazaki, T. & Lemonnier, F.A. Modulation ofthymic selection by expression of an immediate-early gene, early growth response 1 (Egr-1). J.
Exp. Med. 188:715-723 (1998).
15. Miyazaki, T. Two distinct steps during thymocyte
maturation from CD4-CD8- to CD4+CD8+ distinguished in the early growth response (Egr)-1transgenic mice with a recombinase-activating
gene deficient background. J. Exp. Med. 186:

385

877-885. (1997).
16. Miyazaki, T., Müller, U. & Campbell, K.S. Normal development but differentially altered proliferative responses of lymphocytes in mice lacking
CD81. EMBO. J. 16: 4217-4225. (1997).
17. Miyazaki, T., Wolf, P., Tourne, S., Waltzinger, C.,
Dierich, A., Barois, N., Ploegh, H., Benoist, C. &Mathis, D. Mice lacking H2-M complexes, enigmatic elements of the MHC class II peptide-loading pathway. Cell 84: 531-541 (1996).
18. Miyazaki, T., Dierich, A., Benoist, C. & Mathis D.
Independent modes of natural killing distinguished in mice lacking Lag3. Science 272: 405408 (1996).
19. Miyazaki, T., Matsuda, Y., Toyonaga, T., Miyazaki,J., Yazaki, Y. & Yamamura, K. Prevention of
autoimmune insulitis in non-obese diabetic miceby expression of major histocompatibility complex class I Ld molecules. Proc. Natl. Acad. Sci.
USA. 89: 9519-9523 (1992).
20. Miyazaki, T., Uno, M., Uehira, M., Kikutani, H.,
Kishimoto, T., Kimoto, M., Nishimoto, H., Miyazaki, J. & Yamamura, K. Direct evidence for thecontribution of the unique I-ANOD to the development of insulitis in non-obese diabetic mice.
Nature 345: 722-724 (1990).

386

Division of
Basic Medical Sciences (Ⅱ)
Professor
Haruo Kasai, M.D.,Ph.D.

Lecturer
Noriko Takahashi, M.D., Ph.D.

Assistant Professors
Masanori Matsuzaki, Ph.D.,

Homepage

Jun Nogichi, Ph.D.,

Junichi Tanaka, Ph.D.

http://www.bm2.m.u-tokyo.ac.jp/

Introduction and Organization
The Center for Disease Biology and Integrative
Medicine (CDBIM) has been established in 2003, andelected Dr. Kasai as the professor of the Division of
Basic Medical Sciences (2) of CDBIM in July of 2004.
Dr. Kasai was in the National Institute for Physiological Sciences at that time, and officially took officein the University of Tokyo in Novermber, 2005. The
Kasai laboratory has moved to the first building ofFaculty of Medicine in January, 2006. Our division
belongs to the Section of Functional Biology in the
Graduate School of Medicine, and our division isnamed the Division of Biophysics in the graduate
school.

Teaching activities
In 2006, we were involved in education of thegraduate school. We have three graduate students inour own graduate school, and one from the Kyoto
University.

Research activities
Functional imaging is a central theme in modern
biology and medicine. All biological functions involvea multitude of interactions at the molecular, cellular,

and system levels, and it is ultimately desirable toperform molecular and cellular imaging in intact
preparations in which the original in vivo functions
are preserved. We have been exploring two-photon
excitation microscopy with a new type of laser, an
infrared femtosecond-pulse laser, as a means toachieve this goal. The two-photon microscope has theability to penetrate deep into tissues and is the only
imaging instrument that allows investigations of intact
tissues at the cellular and molecular levels. Twophoton microscopy can also be readily combined withmolecular biological and other physiological methods,
and it promises to provide important insight into
various biological processes in the coming years. Our
research interests have two main focuses: (1) the dynamics of synapses in the cerebral cortex and (2)exocytosis in both neurons and secretory cells. We
welcome multidisciplinary collaborations to promote
our research goals and to help to adapt the new microscopic techniques and lasers to a wide range of
biomedical applications.
1) Dynamics of synapses in the cerebral cortex. We
have developed a method to stimulate and control
single synapses in the cerebral cortex with the useof two-photon excitation of photoactive glutamate
analogs. Our investigations have revealed that the
major functions of synapses depend on their

387

structure. We have thus shown that small synapses
are ready to learn, enlarging rapidly (within 10 s)after stimulation, whereas large synapses are
structurally stable and act as long-term memory
traces. These observations suggest that learning,memory, and other activities of the brain are mediated by changes in synaptic structure, and thatthey can be directly visualized. Moreover, we are
now in a position to manipulate synaptic plasticity
with a laser beam at the level of the individual
synapse. Such notions and methodology will befurther exploited to understand brain functions
and disorders.
2) Exocytosis is the most essential function of synaptic terminals and secretory cells. Knowledge ofthe mechanisms of and the ability to control exocytosis artificially have been limited, however.
With the use of two-photon excitation-based simultaneous multicolor imaging of various tracers,
we have, for the first time, visualized exocytosis
in intact islets of Langerhans, pancreatic acini, theadrenal medulla, and synaptic preparations. Byfurther extending our approaches, we aim to develop new methods for imaging and control ofsecretory functions and their molecular processes
in the cerebral cortex and secretory tissues.

References
1. Miura A, Yamagata K, Kakei M, Hatakeyama H,
Takahashi N, Fukui K, Nammo T, Yoneda K,
Inoue Y, Sladek FM, Magnuson MA, Kasai H,
Miyagawa J, Gonzalez FJ, & Shimomura I.
Hepatocyte nuclear factor-4alpha is essential for
glucose-stimulated insulin secretion by pancreaticbeta-cells. J Biol Chem. 2006; 281, 5246-5257.
2. Hatakeyama H, Kishimoto T, Nemoto T, Kasai H,
Takahashi N. Rapid glucose sensing by protein
kinase A for insulin exocytosis in mouse pancreatic islets. J. Physiol. 2006; 570: 271-282.
3. Kishimoto T, Kimura R, Liu T-T, Nemoto T, Takahashi N, Kasai H. Vacuolar sequential exocytosis of large dense-core vesicles in adrenal medulla.
EMBO J. 2006; 25: 673-682.
4. Kasai H, Kishimoto T, Nemoto T, Hatakeyama H,
Liu T-T, Takahashi N. Two-photon excitation im-

aging of exocytosis and endocytosis and determination of their spatial organization. Adv. Drug Delivery Rev. 2006; 58: 850-877.Takahashi N, Hatakeyama H, Okado H, Miwa A, Kojima T, Abe T,
Kasai H. Sequential exocytosis of insulin granules
is associated with redistribution of SNAP25. J
Cell Biol 2004;165:255-262.

388

Division of Biomedical Materials
and Systems
Professor
Takashi Ushida, Ph.D.

Associate Professor
Yasuyuki Sakai, Ph.D.

Homepage

http://www.cdbim.m.u-tokyo.ac.jp/

Introduction and Organization
The Division is composed of two laboratories,
Ushida laboratory and Sakai Laboratory. The Divisiontightly collaborates with Faculty of Engineering. Prof.
Ushida is also charged at Department of MechanicalEngineering, where the laboratory members include
Assistant Professor, two Associates and 15 graduate
students (as of April 1, 2004). Prof. Sakai also holds a
position in Institute of Industrial Science (IIS), University of Tokyo. The current laboratory members at
IIS (as of April 1, 2004) include one research associate, one JSPS postdoctoral fellow, one technical assistant, and six graduate students from Department ofChemical System Engineering, Graduate School ofEngineering. In addition, four graduate students who
belong to other universities do research in our laboratory.

Teaching activities
Prof. Ushida and Prof. Sakai are sharing duties forundergraduate and graduate students of both Graduate
School of Medicine and Graduate School of Engineering. They give lectures on biomedical engineering
at Graduate School of Medicine. Prof. Ushida has also
lectures on tissue engineering, advanced biomaterials
and biomechanics at Graduate School of Engineering.
Prof. sakai gives a lecture concerning biosystem engineering at the Chemical System Engineering courseand Bioengineering course at Graduate School of En-

gineering School.

Research activities
Prof. Ushida’s laboratory aims to establish key
technologies for regenerative medicine. One of the
projects of our research targets the hard tissue regeneration, such as cartilage or bone by tissue engineering
technology. Hard tissue engineering requires the control of its shape in addition to the cell accumulationand scaffold play a key role in meeting this requirement. We focus on the development of biocompatible
materials such as synthetic polymer or inorganic materials combined with stem cell biotechnology. Secondly, we try to elucidate mechanisms of cellular responses to physical stimulations such as hydrostaticpressure, shear stress, stretch, through observing intracellular signaling, and to adopt those effects to tissue engineering.
1) Tissue engineering of cartilage or bone defect- Design and development of biocompatible materials
for cartilage or bone using synthetic polymer, inorganic materials or those combination.
- Development of osteoinductive biomaterials hybridized with bioactive substances.
- Order made shaping of scaffolds by router system
according to the graphical images of tissue defects- Establishment of vascular rich graft bed by biomaterials that spur new blood vessel growth.

3892) Cellular signal transduction induced by physicalstimulations- Hydrostatic pressure loading to chondrocytes orarticular cartilage- Shear stress loading to endothelial cells- Stretch loading to endothelial cells, smooth muscle
cells

2.

3.
The general objective of Prof. Sakai’s laboratory is
to organize experimentally human systems or its subsystems such as organ or tissue using cultured humancells for fundamental understanding of systemic responses of a human body or organs and biomedical orenvironmental applications. At present, we need several different technologies to achieve the goal in addition to usual cell culture technologies. These include
in vitro control of the growth and differentiation oforgan stem or progenitor cell populations, cultivation
technologies ranging from micro- to clinically significant-sizes, three-dimensional microfabrication of
biodegradable organ templates, etc. About such topics,
we are actively doing collaborative research withother institutes outside Univ. of Tokyo. The most important thing is to organize these technologies originally derived from different academic backgroundfrom engineering point of view.

4.

5.

6.

7.
3) Engineering of human large internal organs- Design, preparation and in vitro maturation of implantable liver tissue for humans- In vitro control of growth and differentiation ofhepatocyte progenitors- Bottom-up tissue engineering4) Development of in vitro models for human organs
and their applications- Micro-organ model devices- 2D and 3D micro-patterning of cultured cells- Cell-based devices for environmental evaluation- Cell-based simulator for human metabolism- Various tools for systems biology for a whole body

References
1. Shunsuk Iwayoshi, Katsuko Furukawa , Takashi
Ushida, Continuous Visualization of Morphological Cahnges in Endothelial Cells in Response to8.

Cyclic Stretch, JSME International Journal: C, 49(2) 545-555 (2006)
Fujiwara T, Akita H, Furukawa K, Ushida T, Mizuguchi H, Harashima H., Impact of convective
flow on the cellular uptake and transfection activity of lipoplex and adenovirus, Biol Pharm Bull.
Jul; 29(7):1511-1515 (2006)
Miyata S, Homma K, Numano T, Furukawa K,
Tateishi T, Ushida T., Assessment of fixed charge
density in regenerated cartilage by Gd-DTPAenhanced MRI, Magn Reson Med Sci., Jul; 5(2):73-78 (2006)
Tetsuya TATEISHI, Guoping CHEN, Takashi
USHIDA, Polyfunctional Scaffolds for Tissue
Engineering, J Biomed Sci & Eng 1(1) 8-15
(2006)
Shoogo Ueno, Joji Ando, Hiroyuki Fujita, Tadashi
Sugawara, Yasuhiko Jimbo, Keiji Itaka, Kazunori
Kataoka and Takashi Ushida, The state of the Art
of Nanobioscience in Japan, , IEEE Transactions
on nanobioscience, 5(1) 54-65 (2006)
Y. Cho, T. Yamamoto, Y. Sakai, T. Fujii, B. Kim,
Development of microfluidic device for electrical/physical characterization of single cell, J. Microelectromechanical systems, 15(2), 287-295(2006).
H. Huang, S. Hanada, N. Kojima, and Y. Sakai,
Enhanced Functional Maturation of Fetal Porcine
Hepatocytes in Three-dimensional Poly-L-lactic
Acid Scaffolds: A Culture Condition Suitable forEngineered Liver Tissues in Large-Scale AnimalStudies, Cell Transplantation, 15, 799-809 (2006).
N. Kojima, T. Matsuo, Y. Sakai, Rapid hepatic cellattachment onto biodegradable polymer surfaces
without toxicity using an avidin-biotin binding
system, Biomaterials, 27, 4904-4910 (2006).

390

Division of Clinical Biotechnology
Professor
Kazunori Kataoka, Ph.D.

Associate Professor
Yuichi Tei / Ung-il Chung, M.D., Ph.D.

Lecturer
Keiji Itaka, M.D., Ph.D.
Nobuhiro Nishiyama, Ph.D.

Homepage:

http://www.cdbim.m.u-tokyo.ac.jp/research/01_04.html
http://www.bmw.t.u-tokyo.ac.jp/

Introduction and Organization
Division of Clinical Biotechnology in The Center
for Disease Biology and Integrative Medicine(CDBIM) was established in April 2003. This Division wishes to contribute to the realization of
nanomedicine, which is one of major goals for Research Cluster for Frontier Medicine Development at
The University of Tokyo Hospital and The Center for
NanoBio Integration (CNBI) at The University of Tokyo. We actively collaborate and have an interchangeof graduate students with Graduate Schools of Engineering & Medicine at The University of Tokyo andDivision of Tissue Engineering at The University ofTokyo Hospital. Our division also plays a major rolein the Nano-Bioengineering Education Program(NBEP), which started in 2004 as a novel medicine-engineering interdisciplinary program, and tries
to contribute to the production of medical ventures bypromoting liaison with the industrial sector and to the
production of professionals who understand both advanced medicine and nanotechnology. The divisionconsists of one professor, one associate professor, two
lecturers and several project staff members belonging
to the CNBI and NBEP.
Our division focuses on the realization of
nanomedicine. Nanotechnology, which has recently
been attracting tremendous attention as a leading sci-

entific field in the 21st century, attempts to process
and assemble materials with precision at theatomic/molecular level to produce units with sophisticated functions. Nanodevices produced bynanotechnology integrate materials and systems on ananometer scale, and hold the key to realizing the futuristic medical system that can serve the needed
function at the right time and the right place withminimal invasiveness. Furthermore, nanodevices are
expected to become an important interface between
basic biomedical science and clinical medicine byfacilitating the translation of basic achievements into
clinical applications. Our division wishes to produce
revolutionary medical nanodevices based on
nanotechnology and thereby to spread the idea of"Nanomedicine" intranationally and internationally.

Teaching activities
Traditional medicine-engineering interdisciplinary
programs have focused on the exchange of researchers
and the promotion of collaborative researches between
these two different academic areas. However, the next
generation medicine such as "minimum-invasive diagnosis-treatment" and "targeting medical treatment"
and nanotechnologies are developing so quickly withincreasing complexity that scholars in both areas findit hard to understand each other. For this reason, it is391

becoming increasingly difficult for medical doctors tolocate technological seeds meeting their medical
needs and for engineers to find ways of applying theirtechnological seeds to corresponding medical needs.
This situation prevents the effective development ofrevolutionary medical diagnostical and therapeutic
inventions. Division of Clinical Biotechnology intends
to create an optimal milieu where undergraduate andgraduate students from the medical and engineering
fields can respect each other's background, ignores theboundary and study the fusion area in order to achieve
the common goal of developing intelligent nanodevices for the futuristic medical system.

Research activities
Drug delivery to the targeted site is strongly desired
to enhance the drug function and minimize the side
effects. In this regard, drug delivery systems based on
self-assemblies of block copolymers (i.e., polymeric
micelles) recently draw much attention as one of the
medical applications of the nanotechnology. Block
copolymers spontaneously form polymeric micelles,
which are characterized by the core-shell structure andthe size of ~100 nm, in aqueous media. The core of
the micelles behaves as a nanoreservoir for drugs,
while the coronal shell providing the biocompatible
surface. Polymeric micelles can incorporate a varietyof drugs including hydrophobic drugs, metal complex
drugs, and macromolecular drugs such as proteins andDNA, and release them in a sustained manner or in
response to environmental changes such as pH. The
site-specific drug delivery can be achieved by conjugation of the pilot molecules on the surface of polymeric micelles. Thus, polymeric micelles behave as
intelligent chemical nanomachines for the drug targeting.
The long-circulation of drug carriers is a requisite
for the successful drug targeting. The main obstacles
to long-circulatio are considered to be glomerular excretion in the kidney and recognition by the reticuloendothelial system (RES) located at the liver, spleen
and lung. Polymeric micelles can escape from thosebarriers in the body, resulting in stable blood circulation. Another advantage of using polymeric micelles istheir preferential accumulation in solid tumors, whichmight be due to microvascular hyperpermeability andimmature lymphatic system in tumor tissues. We havesucceeded in the tumor-selective delivery of several
antitumor drugs including adriamycin (ADR) and cisplatin (CDDP) by polymeric micelles, and observed
enhanced antitumor activity with reduced side effects.
These micellar formulations are currently being tested
in clinical trials.
Recently, plasmid DNA (pDNA) and siRNA are receiving much attention as promising tools for thetreatment of genetic and intractable diseases. One of
the major requirements for therapeutic use of pDNA
and siRNA is the development of gene vectors, which
can safely and effectively deliver them into specificcells and regulate their expressions. Recently, we have
prepared polymeric micelles incorporating pDNA
through the electrostatic interaction between DNA andpositively charged block copolymers. The polymeric
micelles protected the loaded DNA from degradation
by nuclease attack and showed efficient gene transfer
to a variety of cells. Also, various smart functions
such as the targeting ability and environmental sensitivity can be integrated with polymeric micelles, offering the opportunities to develop effective synthetic
vectors resembling viral functions. Recently, we havedeveloped the light-responsive gene carriers, and haveachieved in vivo gene transfer in a light-specificmanner. Further, polymeric micelles can be used forthe tissue engineering without cell transplantation.
Recently, polymeric micelles carrying pDNA encoding osteogenic factors were implanted to mouse calvaria bone defects in the form of calcium phosphate
paste, resulting in rapid induction of bone regeneration. Thus, polymeric micelles are expected as useful
nanocarriers of pDNA and siRNA for in vivo use.

References
1. N. Nishiyama, Nanomedicine: Nanocarriers shapeup for long life. Nature Nanotechnology 2(4):203-204 (2007)
2. Y. Lee, S. Fukushima, Y. Bae, S. Hiki, T. Ishii, K.
Kataoka, A Protein Nanocarrier from ChargeConversion Polymer in Response to Endosomal
pH. J. Am. Chem. Soc. 129 (17) 5362-5363(2007)
3. I. A. Khalil, K. Kogure, S. Futaki, S. Hama, H.
Akita, M. Ueno, H. Kishida, M. Kudoh, Y.

392Mishina, K. Kataoka, M. Yamada, H. Harashima,
Octaarginine-modified multifunctional envelopetype nanoparticles for gene delivery. Gene Ther.
14 (8) 682-689 (2007)
4. M. R. Kano, Y. Bae, C. Iwata, Y. Morishita, M.
Yashiro, M. Oka, T. Fujii, A. Komuro, K. Kiyono,
M. Kamiishi, K. Hirakawa, Y. Ouchi, N. Nishiyama, K. Kataoka, K. Miyazono, Improvement ofcancer-targeting therapy, using nanocarriers for
intractable solid tumors by inhibition of TGF-beta
signaling. P. Natl. Acad. Sci. USA. 104 (9) 34603465 (2007)
5. M. Kumagai, Y. Imai, T. Nakamura, Y. Yamasaki,
M. Sekino, S. Ueno, K. Hanaoka, K. Kikuchi, T.
Nagano, E. Kaneko, K. Shimokado, K. Kataoka,
Iron hydroxide nanoparticles coated with poly
(ethylene glycol)-poly(aspartic acid) block copolymer as novel magnetic resonance contrast
agents for in vivo cancer imaging. Colloids Surf.,
B Biointerfaces 56 174-181 (2007)
6. J. -S. Park, Y. Akiyama, Y. Yamasaki, K. Kataoka,
Preparation and characterization of polyion complex micelles with a novel thermosensitive poly
(2-isopropyl-2-oxazoline) shell via the complexation of oppositely charged block ionomers.
Langmuir 23 (1) 138-146 (2007)
7. Arnida, N. Nishiyama, N. Kanayama, W. -D. Jang,
Y. Yamasaki, K. Kataoka, PEGylated gene nanocarriers based on block catiomers bearing ethylenediamine repeating units directed to remarkableenhancement of photochemical transfection. J.
Control. Release 115 (2) 208-215 (2006)
8. J. -S. Park, K. Kataoka, Precise control of lower
critical solution temperature of thermosensitivepoly(2-isopropyl-2-oxazoline) via gradient copolymerization with 2-ethyl-2-oxazoline as a hydrophilic comonomer. Macromolecules 39 (19)6622-6630 (2006)
9. N. Nishiyama, Arnida, W. -D. Jang, K. Date, K.
Miyata,K. Kataoka, Photochemical enhancementof transgene expression by polymeric micelles
incorporating plasmid DNA and dendrimer-based
photosensitizer. J. Drug Target. 14 (6) 413-424(2006)
10. W. -D. Jang, Y. Nakagishi, N. Nishiyama, S.
Kawauchi, Y. Morimoto, M. Kikuchi, K. Kataoka,
Polyion complex micelles for photodynamic

therapy: incorporation of dendritic photosensitizer
excitable at long wavelength relevant to improved
tissue-penetrating property. J. Control. Release
113 (1) 73-79 (2006)
11. W. Kim, Y. Yamasaki, K. Kataoka, Developmentof a fitting model suitable for the isothermal titration calorimetric curve of DNA with cationicligands. J. Phys. Chem. B 110 (22) 10919-10925(2006)
12. Koide, A. Kishimura, K. Osada, W. -D. Jang, Y.
Yamasaki, K. Kataoka, Semipermeable polymer
vesicle (PICsome) self-assembled in aqueous medium from a pair of oppositely charged block copolymers:
physiologicallystablemicro-/
nanocontainers of water-soluble macromolecules.
J. Am. Chem. Soc. 128 (18) 5988-5989 (2006)
13. M. M. Ali, M. Oishi, F. Nagatsugi, K. Mori, Y.
Nagasaki, K. Kataoka, S. Sasaki, Intracellular inducible alkylation system that exhibits antisense
effects with greater potency and selectivity than
the natural oligonucleotide. Angew. Chem. Int. Ed.
45 (19) 3136-3140 (2006)
14. M. Oishi, K. Kataoka, Y. Nagasaki, pHresponsive three-layered PEGylated polyplex micelle based on a lactosylated ABC triblock copolymer as a targetable and endosome-disruptive
nonviral gene vector. Bioconjugate Chem. 17 (3)677-688 (2006)
15. Y. Kakizawa, S. Furukawa, A. Ishii, K. Kataoka,
Organic-inorganic hybrid-nanocarrier of siRNAconstructing through the self-assembly of calcium
phosphate and PEG-based block aniomer. J. Control. Release 111 (3) 368-370 (2006)
16. N. Kanayama, S. Fukushima, N. Nishiyama, K.
Itaka, W. -D. Jang, K. Miyata, Y. Yamasaki, U. -I.
Chung, K. Kataoka, A PEG-based biocompatible
block catiomer with high buffering capacity forthe construction of polyplex micelles showing efficient gene transfer toward primary cells.
ChemMedChem 1 (4) 439-444 (2006)

393

Division ofEnvironmental Health Sciences
Professor
Chiharu Tohyama, Ph.D., Dr.Med.Sci.

Associate Professor
Seiichiroh Ohsako, Ph.D., D.V.M.

Assistant Professor
Masaki Kakeyama, Ph.D.

Project Research Associate
Wataru Yoshioka, Ph.D.

Homepage

http://env-health.m.u-tokyo.ac.jp

Introduction and Organization
Division of Environmental Health Sciences is alaboratory established as a part of the Center for Disease Biology and Integrative medicine, and comprisesof Professor, Associate Professor, and Assistant Professor and other staff members as well as postdoctoral
fellows, graduate and undergraduate students. The
laboratory settings have been renovated, which makes
it possible to start research and educational activities
in full capacity as of January, 2006. Staff members
have been engaged in environmental toxicology formany years at the National Institute for Environmental
Studies, Tsukuba, and the mission of this division forresearch and education is described below.

Research activities
Humans are exposed in our environment to various
hazardous chemicals via food, air, and water. Whenthese chemicals are absorbed, distributed and metabolized in the body, perturbation of homeostasis andadverse signs and symptoms of toxicity may occur. At
the Division of Environmental Health Sciences, theadverse effects caused by exposure to an individual

chemical or to mixtures of chemicals are identified,the dose response relationship for causing the adverse
effects is determined, and the precise mechanism bywhich the toxicity is produced at the molecular andcellular level is elucidated by using two approaches.
The first approach is based on ‘forward toxicology’.
Here we start from a specific disease or health problem humans are facing in the real world that might becaused by exposure to certain chemicals in our environment and we determine if the adverse effects
caused by exposure to the particular chemical or mixture of chemicals are similar to the adverse effects
associated with the human disease or human healthproblem. This is done by exposing laboratory animals
and cultured cells to increasing doses of the chemicalor chemical mixture and identifying adverse effects,
called ‘endpoints of toxicity’, at each dose.
The other approach is ‘reverse toxicology’. In thisapproach we utilize a particular laboratory animalmodel in which a specific adverse effect can be reproducibly observed, and we attempt to clarify thephysiological significance of altered expression ofgenes and proteins in causing the adverse effect. In
this ‘reverse toxicology’ approach we use modern,molecular biology based technologies such as global
gene analysis and genetic engineering to identify the394mechanism of toxicity at the molecular and cellularlevels.
The primary goal of the Division’s research program is to elucidate toxicity mechanisms for various
environmentally hazardous chemicals. To achieve thisgoal, ‘forward and reverse toxicology’ approaches areused to determine how adverse responses of laboratory animals, which are used as an experimental substitute for humans, to a particular chemical are similar
to or different from the adverse responses of humans.
The outcomes of our research provide not only fundamental information for human health risk assessment that can lead to the establishment of adequate
margins of safety for human exposure to environmental chemicals. They give the general public agreater sense of security in their surroundings andthey provide clinical medicine and the basic life sciences new knowledge that is human health relevant.
Division’s Research Themes
1. Elucidation of mechanisms of toxicity at the molecular and cellular level for adverse effects of environmentally hazardous chemicals (dioxin, PCBs,
and heavy metals).
2. Identification of differences in susceptibility to thetoxicity caused by a particular environmentallyhazardous chemical between different animal species and between different genetic strains of thesame species.
3. Determination of the cause of such species andstrain differences in sensitivity to an environmental toxicant at the molecular and cellular level.

Teaching activities
Unfortunately, ‘environmental health’ is not fairly
placed in the curriculum of medicine, pharmacy,
nursing, and other allied health sciences at most universities. In addition to its research mission, the Division of Environmental Health Sciences has an equallyimportant education mission. The Division is actively
involved in educating graduate students and training
postdoctoral fellows to become promising scientist
leaders in the field of environmental health sciences in
the future.
For the upcoming year, the Division will be responsible for a full credit course on ‘Principles and Appli-

cations of Environmental Health Sciences’. In addition, several lectures are to be given to graduate students for Master’s degree as well as to undergraduate
students at School of Medicine and School of Health
Sciences and Nursing.

Publications
1. Tse D, Langston RF, Kakeyama M, Bethus I,
Spooner PA, Wood E, Morris RGM. Schemas andmemory consolidation. Science, 316:76-82.2007
2. Sakata Y., Yoshioka W., Tohyama C., and Ohsako
S. Internal genomic sequence of human CYP1A1
gene is involved in superinduction of dioxininduced CYP1A1 transcription by cycloheximide.
Biochem Biophys Res Comm 355, 687-692, 2007.
3. Kobayashi K, Kuroda J, Shibata N, Hasegawa T,
Seko Y, Satoh M, Tohyama C, Takano H, Imura N,
Sakabe K, Fujishiro H, Himeno S. Induction of
metallothionein by manganese is completely dependent on interleukin-6 production. J Pharmacol
Exp Ther. 320:721-727, 2007
4. Ishimura R., Kawakami T., Ohsako S., Nohara K.
and Tohyama C. Suppressive effect of 2,3,7,8tetrachlorodibenzo-p-dioxin on vascular remodeling that takes place in the normal labyrinth zoneof rat placenta during late gestation. Toxicol. Sci.,
91: 265-274, 2006
5. Tsukahara S, Kakeyama M, Toyofuku Y. Sex differences in the level of Bcl-2 family proteins andcaspase-3 activation in the sexually dimorphic
nuclei of the preoptic area in postnatal rats. J
Neurobiol. 66:1411-1419, 2006
6. Nakajima D, Tin-Tin-Win-Shwe, Kakeyama M,
Fujimaki H, Goto S. Determination of toluene inbrain of freely moving mice using solid-phasemicroextraction technique. Neurotoxicology, 27:
615-618, 2006
7. Shwe TT, Yamamoto S, Kakeyama M, Kobayashi
T, Fujimaki H. Effect of intratracheal instillationof ultrafine carbon black on proinflammatory cytokine and chemokine release and mRNA expression in lung and lymph nodes of mice. Toxicol
Appl Pharmacol. 209:51-61, 2006
8. Tin-Tin-Win-Shwe, Yamamoto S, Ahmed S,
Kakeyama M, Kobayashi T, Fujimaki H. Braincytokine and chemokine mRNA expression in395

mice induced by intranasal instillation with ultrafine carbon black. Toxicol Lett. 163:153-160,
2006.
9. Nishimura N, Yonemoto J, Nishimura H, Tohyama C. Localization of cytochrome P450 1A1
in a specific region of hydronephrotic kidney of
rat neonates lactationally exposed to 2,3,7,8tetrachlorodibenzo-p-dioxin. Toxicology. 227:117-126, 2006.
10. Mitsui T, Sugiyama N, Maeda S, Tohyama C,
Arita J. Perinatal exposure to 2,3,7,8tetrachlorodibenzo-p-dioxin suppresses contextual
fear conditioning-accompanied activation of cyclic AMP response element-binding protein in the
hippocampal CA1 region of male rats. Neurosci
Lett. 398: 206-210, 2006
11. Nohara K, Ao K, Miyamoto Y, Ito T, Suzuki T,
Toyoshiba H, Tohyama C. Comparison of the
2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD)induced CYP1A1 gene expression profile in lymphocytes from mice, rats, and humans: Most potent induction in humans. Toxicology. 225: 204213, 2006
12. Kawakami T., Ishimura R., Nohara K., Takeda K.,
Tohyama, C. and Ohsako, S. Differential susceptibilities of Holtzman and Sprague-Dawley rats tofetal death and placental dysfunction induced by
2,3,7,8-teterachlorodibenzo-p-dioxin(TCDD)
despite the identical primary structure of the arylhydrocarbon receptor. Tox. Appl. Pharmacol. 212:224-236, 2006
13. Shiizaki K., Ohsako, S., Koyama, T., Nagata R.,
Yonemoto, J. and Tohyama, C. Lack of CYP1A1
expression is involved in unresponsiveness of thehuman hepatoma cell line SKHEP-1 to dioxin.
Toxicol. Lett. 160: 22-33, 2005
14. Inouye K, Pan X, Imai N, Ito T, Takei T, Tohyama
C, Nohara K.:cell-derived IL-5 production is asensitive target of 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) Chemosphere 60: 907-913, 2005
15. Nishimura N, Yonemoto J, Miyabara Y, Fujii-Kuriyama Y, Tohyama C.: Altered thyroxin andretinoidmetabolic
response
to2,3,7,8tetrachlorodibenzo-p-dioxin in aryl hydrocarbon
receptor-null mice. Arch Toxicol 79: 260-267,
2005
16. Ikeda M, Mitsui T, Setani K, Tamura M, Kake-yama M, Sone H, Tohyama C, Tomita T.: In utero
and lactational exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin in rats disrupts brain sexual differentiation. Toxicol Appl Pharmacol. 205:
98-105, 2005.
17. Nohara K, Pan X, Tsukumo S, Hida A, Ito T, Nagai H, Inouye K, Motohashi H, Yamamoto M, Fujii-Kuriyama Y, Tohyama C.: Constitutively active
aryl hydrocarbon receptor expressed specificallyin T-lineage cells causes thymus involution andsuppresses the immunization-induced increase insplenocytes. J Immunol. 174: 2770-2777, 2005.
18. Nishimura N, Yonemoto J, Nishimura H, Ikushiro
S, Tohyama C.: Disruption of thyroid hormone
homeostasis at weaning of Holtzman rats by lactational but not in utero exposure to 2,3,7,8tetrachlorodibenzo-p-dioxin. Toxicol Sci. 85: 607614. 2005.

396

Section of Animal Research,
Division of Research Resources
and Support
Professor
Akio Nomoto, Ph.D.

Assistant Professor
Ken-Ichi Hanaki, D.V.M., Ph.D.,

Homepage

Haruyuki Hirata, D.V.M., Ph.D.

http:// www.cdbim.m.u-tokyo.ac.jp/research/01_06.html

Introduction and Organization
Section of Animal Research (formerly Animal Center for Biomedical Research) was established in April
1971 to provide laboratory animal husbandry and veterinary consultation services for the investigators in
the Faculty of Medicine. A full-time teaching staff, aveterinarian, was arrived in April 1972. The building
was completed in March 1973, and the center began toprovide services for animal experimentation in April
1973. The building has 7 floors and the basement.
Basement; operating room for plants, central heating
plant room, electric-transformation room, animal
quarantine rooms, etc.
1st Floor; office rooms, conference room, dressing
room, etc.
2nd Floor; staff rooms, laboratories for this section
staff, cage washing rooms, rabbit and rat rooms.
3rd Floor; SPF rodent rooms.
4th Floor; SPF rodent rooms and radioisotope laboratories.
5th Floor; procedure rooms (autopsy, surgery, x-ray)and no-human primate rooms.
6th Floor; no-human primate, dog, pig rooms.
7th Floor; air-conditioning plant room.
The building is repaired entirely this year.
Animal Center for Biomedical Research was at firsta facility attached to the faculty. Today the animal
center is one of sections, Division of Research Re-

sources and Support, the Center for Disease Biology
and Integrative Medicine (CDBIM).
The members of this section are 3 teaching staffs, 2technical support staffs, head official of CDBIM, ateaching assistant, 3 assistant laboratory animal technicians, and 4 assistance clerks. In addition, about 10
contracted employees work together with us in thebuilding to maintain the facilities; animal care,
air-conditioning, cage-washing, etc. One of our missions is to provide quality care for all animals used inour building. The other is to assist the registered users
in their mission of quality research with respect to theuse of laboratory animals. In particular, assistant professors (attending veterinarians) have overall responsibility for the health and welfare of animals used inresearch. The office of this section is also the secretariat of the Animal Care and the Use Committee ofGraduate School of Medicine, the University of Tokyo(IACUC). We check submitted animal experimentplans to the committee whether the plans would be
carried out in consideration of animal welfare, andthen give comment and/or advice to the principal investigator. The committee (Chair, Prof. Akio Nomoto)will review the latest plans and will approve, withhold
approval, or require modifications to secure approvalin accordance with law, regulations and University
policies governing the use of animals.
All investigators in the University of Tokyo are able
to use facilities in our building after the registration.

397

However the most of registered patrons are the investigators in the Graduate School of Medicine. The
number of registered patrons was 670 in 2007.

Teaching activities
Our teaching responsibility is to give lectures on
Laboratory Animal Science to the 2nd-year students of
the Science Course III of the College of Arts and Sciences. The teaching staff of this section teaches thefollowing subjects.
(i) Animal Welfare, Law, Rules and Regulations(ii) Refinement of Animal Experiments (Anesthesia
and Euthanasia)(iii) Animal Breeding and Animals Used in Medical
Science(iv) Infectious dieseases of Laboratory Animals andZoonoses
There is no regular teaching curriculum for graduate students. However Laboratory Animal Science istaught as a part of Microbiology.

Research activities
Each assistant professor has own research theme,
and they are responsible for the research in this section. Followings are the research profiles.
(i) Detection of a trace amount of antigen in tissue.
The purpose of this research is the development of asignal amplification technique suitable for the detection of antigen in tissue. We have developed a newsignal amplification technique using nucleic acid thatwould be suitable for the detection of immobilized
antigen on protein chip or tissue. Now we try to adapt
the technique for the detection of PrPBSE in brain. This
study is collaboration with National Institute of Infectious Diseases (NIID).
(ii) Elucidation of the mechanisms to escape hostimmunity by pathogen in parasitic infections.
We expect this investigation will be helpful for thedevelopment of new therapeutic approaches anddrugs.

References
1. Fujiyuki T, Ohka S, Takeuchi H, Ono M, Nomoto
A, Kubo T. Prevalence and phylogeny of Kakugo

virus, a novel insect picorna-like virus that infects
the honeybee (Apis mellifera L.), under various
colony conditions. J Virol. 2006;80:11528-38.

398

Section of Radiation Biology
Professor
Kiyoshi Miyagawa, M.D.,Ph.D.

Associate Professor
Yoshio Hosoi, M.D.,Ph.D.

Lecturer
Takahiko Suzuki, Ph.D.

Associate
Yoshihisa Matsumoto, Ph.D.,

Atsushi Enomoto, Ph.D.,

Mari Katsura, M.D.,Ph.D.,

Noriko Hosoya, M.D.,Ph.D.

Homepage

http://www.cdbim.m.u-tokyo.ac.jp/

Introduction and Organization
The Section of Radiation Biology belongs to theDivision of Research Resources and Support in Center
for Disease Biology and Integrative Medicine. The
main duty of the section is to support the use of radioisotope at Graduate School of Medicine. Historically,in 2003, the Department of Radiation Oncology andthe Radiation Research Institute were joined to form a
new department.
To maintain the facility of radiation research, responsible staffs at two facilities are elected from ourdepartment. Although the law that regulates the use ofradioisotope in Japan was largely revised this year, themaintenance system and frequency of the use of radioisotope have not been changed.
Present staffs came from the previous departments.
However, the position of the professor had been vacant since 2003. The present professor took the position on 16 June 2005. Since then, the new research
projects have been carried out.
Although the supportive work is very important,education and research on effects of radiation on human bodies are the most important duties in this section. We cannot deny the fact that individual works
have not been integrated thus far, the present staffs areconstructing a new group that plays a leading role inradiation biology.

Teaching activities
We are responsible for the education of basic radiation medicine for the 2nd year medical students. The
students are expected to start with understanding of
the physics and the chemistry for radiation and thenunderstand the basic biology of radiation. After that,they learn how to handle radioactive materials by the
2-day practical course.
In addition to these courses, a new course for the
4th year medical students was opened this year. The
students are expected to learn how to use clinical radiation technology safely in hospitals. The background for this addition is that clinical problems arising from the lack of knowledge of radiation effects
have been increasing. Furthermore, the education ofradiation casualty medicine is included in this new
course. Even though radiation casualty is rare, all clinicians should know how to treat patients exposed toradiation.
We also take part in the education of radiation
health science for the 3rd year students specialized inhealth science. Radiation protection is emphasized in399

this course.
At Graduate School of Medicine, molecular biology
of DNA damage response to radiation is more emphasized.
In addition, education courses for users of radioactive materials frequently take place.

Research activities
Before the present professor took the position, avide range of radiation biology, including biologicaleffects of low-dose irradiation, non homologous end
joining (NHEJ) for DNA double-strand breaks, apoptosis that responds to DNA damage, and radio-sensitization had been topics in this department.
Since 2005, homologous recombinational repair has
been the main subject.
RecA in E. coli and its homolog Rad51 in budding
yeast play a central role in homologous recombinational repair. Historically, mechanism of homologous
recombination was extensively studied in these organisms, whereas homologous recombination had beenrecognized as a minor pathway of DNA double-strand
break repair in higher organisms. However, subsequent studies revealed that homologous recombination
as well as NHEJ plays an important role in DNA double-strand break repair in higher organisms. There are
two major differences between these two pathways.
NHEJ functions at any stages of the cell cycle,
whereas homologous recombination is restricted to the
S to M phases. Another difference is that NHEJ is anerror-prone repair pathway and homologous recombination is an error-free repair pathway.
We have been studying on the functions of Rad51
paralogs, which share structural similarity with Rad51.
There are five genes that belong to this paralog family
in mitotic cells. Although they share structural similarity with each other, there is no functional redundancy. To clarify their roles, we have generated theirmutant human cells by gene targeting and RNA interference.
Rad51B dysfunction due to chromosomal translocations has been found in some benign tumors, particularly in uterine leiomyomas. In Rad51B mutant
cells, the Rad51-dependent recombinational repair
pathway is impaired. In addition, centrosome fragmentation and aneuploidy were found to be increasedin these cells. Haploinsufficiency of the gene causes
these aberrations. Thus, Rad51B plays a role in centrosome and chromosome integrity.
In contrast to early stages of homologous recombination, little is known about the mechanisms of homologous recombination at late stages. The
Mus81-Eme1 complex has been shown to resolve recombination intermediates. Subsequent studies revealed that this enzyme plays a role in the resolutionof stalled replication forks. We have studied on thefunction of this complex in human cells. Unexpectedly,
the mutant cells are hypersensitive to DNA crosslinking agents rather than to replication inhibitors. The
growth of the mutant cells was reduced by the Chk1
and Chk2-dependnet checkpoint activation at the S
and G2 phases, leading to the reduction in Cdk1 andCdk2 functions. Chromosome analysis revealed thatthe frequency of chromosome doubling was significantly increased in the mutant cells. Restoration of
Cdk1 activity by ectopic expression reduced the frequency of chromosome doubling, suggesting that thecheckpoint activation may cause chromosome doubling.
Thus, the impaired recombinational repair pathway
is associated with numerous chromosomal aberrations.
It is established that some breast cancers arise fromdefective recombination. It is also possible that othercancers are caused by the similar processes. Furthermore, we hypothesize that non-cancerous diseases canbe associated with DNA damage responses. The study
on homologous recombination also contributes to thedevelopment of radiation therapy. Radiation andDNA-damaging chemotherapeutic agents induce DNA
double-strand breaks, which can be normally repairedby the intrinsic repair pathways. The induced breaks
therefore do not always lead to apoptosis. If we will
understand the details of the repair pathways, themolecules in this pathway will be the therapeutic targets. From the clinical point of view, we will establish
the basic science of homologous recombinational repair.

References
1. Sarai N, Kagawa W, Kinebuchi T, Kagawa A, Tanaka K, Miyagawa K, Ikawa S, Shibata T, Kurumizaka H, Yokoyama S. Stimulation of Dmc1-

400

2.

3.

4.

5.

6.

7.

8.

9.

mediated DNA strand exchange by the humanRad54B protein. Nucleic Acids Res. 2006;34:
4429-4437.
Hosoi Y, Kapp LN, Murnane JP, Matsumoto Y,
Enomoto A, Ono T, Miyagawa K. Suppression ofanchorage-independent growth by expression of
the ataxia-telangiectasia group D complementating gene, ATDC. Biochem Biophys Res Commun.
2006;348:728-734.
Tonotsuka N, Hosoi Y, Miyazaki S, Miyata G,
Sugawara K, Mori T, Ouchi N, Satomi S, Matsumoto Y, Nakagawa K, Miyagawa K, Ono T. Heterogeneous expression of DNA-dependent protein
kinase in esophageal cancer and normal epithelium. Int J Mol Med. 2006;18:441-447.
Date O, Katsura M, Ishida M, Yoshihara T, Kinomura A, Sueda T, Miyagawa K. Haploinsufficiency of RAD51B causes centrosome fragmentation and aneuploidy in human cells. Cancer Res.
2006;66:6018-6024.
Hiyama T, Katsura M, Yoshihara T, Ishida M,
Kinomura A, Tonda T, Asahara T, Miyagawa K.
Haploinsufficiency of the Mus81-Eme1 endonuclease activates the intra-S-phase and G2/M
checkpoints and promotes rereplication in humancells. Nucleic Acids Res. 2006;34:880-892.
Adachi N, So S, Iiizumi S, Nomura Y, Murai K,
Yamakawa C, Miyagawa K, Koyama H. The human pre-B cell line Nalm-6 is highly proficient ingene targeting by homologous recombination.
DNA Cell Biol. 2006;25:19-24.
Nakagawa K, Kanda Y, Yamashita H, Hosoi Y,
Oshima K, Ohtomo I, Ban N, Yamakawa, S, Nakagawa S, Chiba S. Preservation of ovarian function by ovarian shielding when undergoing total
body irradiation for hematopoietic stem celltransplantation: a report of two successful cases.
Bone Marrow Transplant. 2006;37:583-587.
Li Z, Hosoi Y, Cai K, Tanno Y, Matsumoto Y,
Enomoto A, Morita A, Nakagawa K, Miyagawa K.
Src tyrosine kinase inhibitor PP2 suppresses
ERK1/2 activation and epidermal growth factor
receptor transactivation by X-irradiation. Biochem
Biophys Res Commun. 2006;341:363-368.
Someya M, Sakata K, Matsumoto Y, Yamamoto
H, Monobe M, Ikeda H, Aono K, Hosoi Y, Suzuki
N, Hareyama M. The association of DNA-dependent protein kinase activity with chromosomal instability and risk of cancer. Carcinogenesis. 2006;27: 117-122.
10. Morita A, Zhu J, Suzuki N, Enomoto A, Matsumoto Y, Tomita M, Suzuki T, Ohtomo K, Hosoi Y.
Sodium orthovanadate suppresses DNA damage-induced caspase activation and apoptosis byinactivating p53. Cell Death Differ. 2006;13:499-511.

401

Section of Bioinformatics
AssociateKenji Hatano, M.D.

Homepage

http://www.cdbim.m.u-tokyo.ac.jp/

Organization
Section of Bioinformatics started in 2003 as a division of Research and Support of the Center for Disease Biology and Integrative Medicine. Targeting biomedical research support using information technologies, this division performs management and maintenance of the research network and information servers
working with the Information Promoting Office of the
Graduate School of Medicine.

Research activities
Medical terminology and ontology:
Standardization and systematization of medical vocabularies are major issue for appropriate utilizationof medical information implied in various medical
terms. We are committed the working group for theJapanese standard disease code master (standard vocabulary of Japanese disease names) and studying
about the strategies for perform the standardization ofJapanese medical vocabularies for electronic medical
records. Using current techniques of systematizationof terms and concepts, such as terminology or ontology, we are testing systematization of Japanese medical terms and concepts and automatic classification
system for free medical words.
Distributed processing system for medical terms:
As an efficient method for the distribution of medical term information and promotion of the standard
vocabularies, we focused distributed processing system using the network and are developing distributed
methods service system in the internet for evaluationof utilities and effectiveness of the system.

Main targets of our research are:z Standardization of medical vocabularies and coding systemz Biomedical terminology and ontology
z Distributed processing system for medical information using the internetz Security of biomedical research networkz Privacy and anonymization of personal data inclinical researchz Digitalization and indexing of old Japanese medical libraries.

References
1. Hatano K., Ohe K. Information Retrieval System
for Japanese Standard Disease-Code Master Using
XML Web Service. J. American Medical Informatics Association. Symposium Suppl. 597, 2003.

402

Office ofInternational Academic Affairs
Head
Kazuhiko Yamamoto

Assistant Professor
Joseph Green
Toshiyuki Maruyama
Christopher Holmes

Homepage

http://square.umin.ac.jp/koryu/homepage10.html

Status and functions
The Office of International Academic Affairs is under the direct authority of the Dean of the Faculty of
Medicine. Its three most important roles, as defined by
the Committee on International Academic Affairs, arei) international educational exchange, ii) international
contacts in research and scientific fields, and iii) international cooperation in health care and medicine.

Activities
This document reports on the office's activities inthese areas over the academic year 2006 (April to
March).
1. International Educational Exchange
1.1 Student counseling about education and research
In 2006, there were 166 foreign students (32 countries) officially registered in the Graduate School of
Medicine. Many inquiries were received during thisperiod from prospective applicants for foreign student
and trainee status: responses were sent to 92 such inquiries.
Many currently enrolled foreign students received
counseling at this office concerning their studies andlife at the University of Tokyo and the requirementsfor obtaining scholarships and degrees.

In addition, a large number of University of Tokyo
students wish to supplement their training with basic
clinical experience overseas before graduation, as wellas the type of short-term training (1-3 months) frequently called clinical electives overseas. Inquiries
from these students were either answered by this office or referred to appropriate centers.
Every year, 20 or more University of Tokyo students go overseas to study, and the office makes its
best efforts to accommodate their needs.
It has become a tradition to hold a Spring
get-together of foreign students and University of Tokyo students who will study or have studied abroad at
the Sanjo Kaikan, a reception hall on the Hongo
campus. It is attended by the Dean of the Faculty of
Medicine, the teaching staff, and students: about 80
people attended this event in 2006.
Another tradition since the mid-1970s is the Autumn foreign students' trip; In 2006, a group of 34
from 11 countries traveled to Tokyo Disney Sea.
The annual Ryugakusei Ronbun Contest was first
held in 1999. As in previous years, in the 2006 Contest foreign students gave oral presentations based on
their research papers to interested fellow students andfaculty, and the five best speakers were given awards.
A formal agreement for academic exchange between the University of Pennsylvania and the University of Tokyo was renewed in May 2004. Since that

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time, five University of Tokyo students have taken
research electives at the University of Pennsylvania
every year, and one student from the University ofPennsylvania has taken a clinical elective at the University of Tokyo.
An agreement on academic cooperation was signed
between the Graduate School of Medicine of the University of Tokyo and Johns Hopkins University inDecember 2002. Since the start of the program in
2002, ten University of Tokyo students visited to attend clinical electives at Johns Hopkins University.
An agreement on academic cooperation was signed
between the Graduate School of Medicine of the University of Tokyo and the University of Michigan
Medical School in January 2005. Since the start of the
program in 2005, four University of Tokyo students
visited to attend clinical electives at the University ofMichigan Medical School, and one student from the
University of Michigan has taken a clinical elective at
the University of Tokyo.
An agreement on academic cooperation was signed
between the Graduate School of Medicine of the University of Tokyo and Munich University in February
2005. Since the start of the program in 2005, one University of Tokyo student visited to attend research
electives at Munich University, and two students from
Munich University have taken clinical electives at the
University of Tokyo.
An agreement on academic cooperation was signed
between the Graduate School of Medicine of the University of Tokyo and Washington Medical School in
November 2005. Since the start of the program in
2005, two University of Tokyo students visited to attend clinical electives at Washington Medical School.
An agreement on academic cooperation was signed
between the Graduate School of Medicine of the University of Tokyo and Taipei Medical University inNovember 2005. Since the start of the program in
2005, one University of Tokyo student visited to attend clinical electives at Taipei Medical University.
An agreement on academic cooperation was signed
between the Graduate School of Medicine of the University of Tokyo and Mahidol University in September
2006. Since the start of the program in 2006, one University of Tokyo students visited to attend research
electives at Mahidol University, and one student from
Mahidol University has taken clinical electives at the

University of Tokyo.
1.2 Counseling University of Tokyo medical students
and researchers about short-term and longer
overseas study programs
Every year, about 30 requests from students forcounseling regarding pre-graduation or postgraduation studies abroad are received by the Officeof International Academic Affairs. The office responds
to these requests by providing information, advice,and letters of recommendation.
2. International contacts in research and scientificfields
2.1 Promotion of academic exchange between Japanand Thailand
Through the good offices of the Japan Society for
the Promotion of Science, a 10-year program of scientific exchange with Mahidol University in Thailand
began in 1999. Quite unlike previous forms of academic exchange, this one is designed from the start toachieve results by focusing clearly on one area of research and on specific outcomes. The focus is on infectious diseases and related fields, within which research projects are underway in nosocomial infections,in new and re-emerging infections, and in other related areas. A total of 19 researchers were invited toJapan (847 researcher-days) and 17 Japanese researchers were sent abroad (124 researcher-days) in2006.
3. Education and research
3.1 Education
In 2006, Dr. Joseph Green and Dr. Toshiyuki Maruyama taught a course open to all students in the
Graduate School of Medicine: Introduction to Clinical
Epidemiology Research.
In 2006, Dr. Green taught a course open to all students in the Graduate School of Medicine: Introduction to Scale Development.
Dr. Green also taught two other graduate-levelclasses: International Epidemiology 1 and 2.
Mr. Christopher Holmes taught Medical English 1,
2, and 3, the first two of which are required for all
medical students. The Office also organized classes inEnglish for the Health Sciences.
In 2006, Dr. Green and Mr. Holmes led ad hoc ses-404

sions in Oral Presentation Training. These sessions
were open to all students and teaching staff in the
Graduate School of Medicine and the Faculty of
Medicine.

References
1. Hanajiri K, Maruyama T, Kaneko Y, Mitsui H,
Watanabe S, Sata M, Nagai R, Kashima T, Shibahara J, Omata M, Matsumoto Y. Microbubbleinduced increase in ablation of liver tumors byhigh-intensity focused ultrasound. Hepatology
Research. 36: 308-314. 2006.
2. Suzukamo Y, Noguchi H, Takahashi N, Shimatsu
A, Chihara K, Green J, Fukuhara S. Validation of
the Japanese version of the Quality of LifeAssessment of Growth Hormone Deficiency in
Adults (QoL-AGHDA). Growth Hormone & IGF
Research 16 (2006) 340–347
3. Green J. Graphs. Chest. 2006;130:620-621.
4. Takahashi H, Suzukamo Y, Nakamura M, Miyachi
Y, Green J, Ohya Y, Finlay AY, Fukuhara S. Japanese version of the Dermatology Life Quality Index: validity and reliability in patients with acne.
Health and Quality of Life Outcomes 2006, 4:46
5. Fukuhara S, Green J, Albert J, Mihara H, Pisoni R,
Yamazaki S, Akiba T, Akizawa T, Asano Y, Saito
A, Port F, Held P, Kurokawa K. Symptoms of depression, prescription of benzodiazepines, and therisk of death in hemodialysis patients in Japan.
Kidney Int. 2006 Nov;70(10):1866-72.
6. Takahashi N, Kikuchi S, Konno S, Morita S, Suzukamo Y, Green J, Fukuhara S. Discrepancy between disability and the severity of low back pain:
demographic, psychologic, and employmentrelated predictors. Spine 2006 Apr 15;31(8):9319; discussion 940.

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The International Research Center
for Medical Education (IRCME)
Director & Professor
Kimitaka Kaga, M.D., Ph.D.

Professor
Kiyoshi Kitamura, M.D., Ph.D.

Associate Professor
Yuko Takeda, M.D., Ph.D.

Lecturer
Hirotaka Onishi, M.D., M.H.P.E.

Homepage

http://www.ircme.u-tokyo.ac.jp

History and organization
Three years after it was first proposed, the University of Tokyo has established International ResearchCenter for Medical Education (IRCME) on 1 April
2000. The Ministry of Education (in 2001 reformed to
Ministry of Education, Culture, Science and Sports),
the University of Tokyo, and the Graduate School of
Medicine positioned IRCME as a base for promotinginternational cooperative studies of medical education.
IRCME consists of three departments of International Cooperative Study for Medical Education,
Planning & Coordination for International Cooperative Projects and Information on Medical Education,and visiting professor from abroad. We hope that the
research in medical education carried out by IRCME
will improve medical education and health care inmany countries.
The mission of IRCME includes research in international cooperation in medical education, research inmedical education, and development of human resource in medical education. Promotion of and contribution to education in the Faculty of Medicine,
University of Tokyo and University of Tokyo Hospitalis also our fundamental role. For these, visiting pro-fessors from abroad have helped us update and reflectin our studies.

International Cooperative Study in
Medical Education
The University of Tokyo, especially the Faculty of
Medicine, takes pride in its academic excellence not
only in Japan but also other foreign countries. Compared with other Western big-name universities, however, activities and research in international cooperation area have been weak. For effective and sustainable cooperation, educational assistance as a methodology takes longer time but will influence people forlong. Educational expertise will strengthen projects
supported by official development assistance.
To fulfill the mission, faculty and staff in this department do research on a wide range of topics in undergraduate and postgraduate medical education. One
goal is to move this field of inquiry forward by putting
into practice the information obtained from actionoriented research done with full appreciation of thepriorities of international cooperation in medical education.
This department also makes important contributions

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to undergraduate and postgraduate medical curricula,in ways that raise awareness of international cooperation and help Japanese medical practitioners developinterest in international activities.

Planning & Cooperation for International Cooperative Projects andInformation on Medical Education
Department of Planning & Coordination for International Cooperative Projects and Information on
Medical Education is responsible for developing international cooperation in health professions education
area (medicine, dentistry, pharmacy, nursing, publichealth, rehabilitation, etc) facilitated by the Ministryof Education, Culture, Sports, Science, and Technology. This department should lead any international
cooperation projects in health professions education
area in Japan and aim at face-to-face and heart-toheart international cooperation. Activities are listed
below.
1. Development of international cooperation projects
in health professions education area budgeted by
official development assistance (ODA), research
grants, etc, especially in developing countries.
Currently, several projects for Afghanistan are
under implementation.
2. Support for international cooperation projects inhealth professions education area through the effort on information gathering and interpersonal
exchange in both domestic and international level.
Currently, we have constructed strong relationshipwith the Committee for International Affair (Japan
Society for Medical Education), National Institutefor Public Health and International Medical Center of Japan in medical area, and St. Luke's College of Nursing in nursing area.

Visiting Professors
IRCME invites specialists from abroad with expertise in medical education and international cooperation to be visiting professors. They advise and instruct
IRCME on planning and on educational activities, andcollaborate with IRCME faculty and staff on educational research.

Through IRCME-sponsored lectures and seminars,
they also provide intellectual stimulation to medical
students, interns, and residents, and introduce new
information on medical education and international
cooperation to a wider audience.
In 2006, we accepted two visiting professors: Helen
Cosgrove, MD, FACP (New Mexico University: November 2005-April 2006), and Linda Snell, MD,
MHPE, FRCPC, FACP (McGill University: October
2006-April 2007). They offered several seminars, lectures for international trainees, and many suggestions.

References
1. Yuko Takeda, Tetsuya Inafuku, Yoshikazu Tasaka,
Junji Otaki, Taichi Takeda, Tsuyoshi Takara, Kiyoshi Kitamura, Robert E. Kristofco. Mailing list
(ML) as a promising tool for e-learning for physicians in a solo practice. Distance Learning and theInternet 2006 Proceeding, Association of Pacific
Rim Universities, (http://apru2006.dir.u-tokyo.ac.
jp/pdf/3c-1.pdf), 2006