
Preface 　　The Institute of Tropical Medicine, Nagasaki University, established in １９４２，is a unique government‐supported institution for the research on tropical medicine, both in the basic and applied fields. Its reorganization led to the first collaborative institute in medical science in Japan in １９８９，and designation as one of the Centers of Excellence in １９９５．Present organization of the institute is composed of３major research fields（１１　departments，１domestic visiting department，１overseas visiting department），２centers, and１clinical unit. 　　In November １９９６，the １４^th International Congress for Tropical Medicine and Malaria was held in Nagasaki, presided by Prof. Emeritus Keizo Matsumoto, with active participation by the staffs of the institute, resulting in the globalization of the institute and its staffs. On this occasion, a memorandum of collaborative research was signed between the institute and the National Institute of Allergy and Infectious Diseases/National Institute of Health. the US. 　　According to the first external review in １９９６， the institute worked out its Mission Statement as shown on a separate page. In １９９８， the Reference Center of the institute was reorganized into Information and Reference Center for Tropical Diseases, which is responsible to provide various information on tropical medicine, in addition to its previous activities. During the Education and Culture Week in １９９７， special exhibition of the Center was carried out in order to improve the understanding on the institute and tropical medicine by the societies. 　　Follow‐up of the participants in the tropical medicine training course was carried out on its ２０^th Anniversary in １９９７． Since a similar course operated at the Institute of Medical Science, the University of Tokyo was closed in １９９９， the course in our institute became the sole training course on tropical medicine in Japan, operating with １５ participants in ２０００． The number of applicant has been in excess to the number of admitted participants during the past several years. Many of them have already been to some tropical areas, and were motivated for further studies through their own experiences. 　　Another group training course "Research on Tropical Medicine" sponsored by JICA was significantly strengthened in １９９７， by extending its period to １２ months, inviting participants nearly from １０ countries. For such activities contributing to the friendship with foreign countries, the institute was officially commended by the Minister of Foreign Affairs of Japan in July １９９８． The title of the certificate endowed to the participants in the group training course was changed from previous "Certificate" to "Diploma". 　　In the year ２０００， the exchange program under the core university system by JSPS was newly established utilizing our institute and National Institute of Hygiene and Epidemiology as the core university in Japan and Vietnam, respectively. This project has drawn much attention by the external scientists as an example of future project type research scheme in which researchers from multiple departments can participate regardless of their different speciality. 　　Memorandom of academic exchange program was signed between Nagasaki university and Mahidol university, Bangkok, Thailand. 　　In the year １９９９， JICA newly established "Developmental Partner Project", and our Malaria Control Project was among subjects approved by the JICA. This would be another overseas research project of the institute. Besides, International Program of Parasitic Diseases. so‐called Hashimoto Initiatives, has been participated by a number of investigators of this institute. 　　According to the current reformation policy of Japanese government, all national university in Japan are scheduled to be independent organizations. This future outlook should be accepted as de facto, followed by appropriate responses. The Institute of Tropical Medicine, Nagasaki University, is also not an exception, and is required to effectively concentrate its resources to appropriate subjects along the line shown in its Mission Statement, towards international contribution in the field of tropical medicine and international health. 　　Kind and generous support to the institute is highly appreciated. １１ August ２０００ Akira Igarashi, MD, PhD Professor and Dean Institute of Tropical Medicine Nagasaki University


Preface　１ Contents　２ Historical Review　３ Successive Deans of the Institute　４ Organizational Chart　５ Collaboration Research　６ Institute of Tropical Medicine Steering Committee　７ Institute of Tropical Medicine Collaboration Professional Committee　８ Scope of Activity　９ Postgraduate School　９ Three‐month Course on Tropical Medicine and Related Studies　９ Training Course in Research of Tropical Medicine　１０ Public Lectures at the Institute　１０ Publications　１０ Department of Virology　１１ Department of Bacteriology　１２ Department of Protozoology　１３ Department of Parasitology　１４ Department of Thermal Adaptation　１５ Department of Biochemistry　１６ Department of Pathology　１７ Department of Internal Medicine　１８ Department of Preventive Medicine and AIDS Research　１９ Department of Medical Entomology　２０ Department of Social Environment　２１ Department of Environmental Physiology　２２ Department of Internal Medicine（University Hospital）　２３ Animal Research Center　２３ Information and Reference Center of Tropical Medicine　２４ Central Laboratory　２４ Library　２５ Administration　２５ Location map of the Institute of Tropical Medicine on Sakamoto Campus of Nagasaki University　２６ Ground plan of the Institute, 1st Floor, 2nd Floor　２７ Ground plan of the Institute, 3rd Floor, 4th Floor　２８ Ground plan of the Animal Research Center　２９ Telephone Number　３０ Contents Historical Review 　　The Institute of Tropical Medicine, Nagasaki University was originally founded in March 1942, as the East Asian Research Institute of Endemics, in order to perform basic and applied studies on endemic diseases in East Asia. At the beginning, most of its research activities were field studies in mainland China, performed by several department such as Pathology, Bacteriology, Internal Medicine and Dermatology of Nagasaki College of Medicine. Unfortunately, all the facilities and research materials were completely destroyed instantaneously along with the Medical School by the atomic bomb which exploded on August 9th, 1945. As a result, development of the institute and its research activities were severely inhibited. 　　In April 1946, the institute was named as the Research Institute of Endemics attached to Nagasaki College of Medicine, and moved to Isahaya City in May in order to resume its research activities. In accordance with the Act on the Foundation of National Schools in May 1949, the institute was renamed as the Research Institute of Endemics, Nagasaki University. Becauce of the severe flood in Isahaya City, the construction of the new building in Sakamotomachi, Nagasaki City was started in 1960, and the institute moved to new building in April, 1961. At that time, there were only two departments, Pathology and Clinics, however, since 1964, new departments were established every Year, such as Epidemiology, Parasitology, Virology and at the end of 1966, the first extension of the building was completed. 　　In June 1967, according to the partial alteration of the Act on the Foundation of National Schools, the name of the institute was changed to the present one, in order to perform basic as well as applied studies on tropical medicine. At the same time, the Department of Internal Medicine of the institute with 20 bed facilities was opened in the University Hospital. In 1974, Department of Bacteriology and Reference Center as an attached facility were opened. In 1978, the Department of Preventive Medicine suppoeted by visiting staff and the Training Course of Tropical Medicine were started. In 1979, Ward of Infectious animals became Animal Research Center. In March 1980, the 2nd extension of the main building was concluded. In September 1983, the Training Course in Research for Tropical Medicine by JICA was opened. In 1984,Department of Protozoology was established. In July 1985, the 3rd extension of the building was completed. In 1987, Department of Medical Entomology was established. In 1989, the institute was reorganized to a collaboration research institute. In 1991, Department of Biochemistry was added. In March 1994, the 4th extension of the building was completed, and in April, 1994, the institute was reorganized to 3 research fields, Tropical Microbiology, Pathogenesis and Clinical Sciences, and Environmental Medicine, with addition of 2 new research departments, Thermal Adaptation and Social Environment, and the institute has 12 research departments at present. In 1995, the Institute was designated as one of the "Centers of Excellence" in the forefront of scientific research. In 1996, a new research department, Molecular Epidemiology, was established under the Research Field of Microbiology to invite an overseas visiting professor. In 1997, the Reference Center was abolished and in its place the Information and Reference Center of Tropical Medicine was established, symbolizing continuous consolidation and re‐organization of the Institute. Animal Research Center The ３rd and ４th extension building including Information and Reference Center of Tropical Medicine, The Institute of Tropical Medicine, Nagasaki University


（East Asian Research Institute of Endemics） Susumu Tsunoo May．４，１９４２‐Aug．２２，１９４５ Kohei Koyano Dec．２２，１９４５‐Jan．２３，１９４８ Kiyoshi Takase Jan．２４，１９４８‐Aug．３１，１９４８ Noboru Tokura Sept．１，１９４８‐May．３０，１９４９（Research Institute of Endemics） Noboru Tokura May．３１，１９４９‐Aug．３１，１９５８ Nanzaburo Omori Sept．１，１９５８‐Nov．３０，１９６３ Hideo Fukumi Dec．１，１９６３‐May．３１，１９６７（Institute of Tropical Medicine） Hideo Fukumi June．１，１９６７‐Nov．３０，１９６９ Daisuke Katamine Dec．１，１９６９‐Nov．３０，１９７３ Kaoru Hayashi Dec．１，１９７３‐Nov．３０，１９７７ Tatsuro Naito Dec．１，１９７７‐Nov．３０，１９７９ Daisuke Katamine Dec．１，１９７９‐Apr．１，１９８１ Keizo Matsumoto Apr．２，１９８１‐Apr．１，１９９１ Hideo Itakura Apr．２，１９９１‐Apr．１，１９９３ Mitsuo Kosaka Apr．２，１９９３‐Apr．１，１９９７ Akira Igarashi Apr．２，１９９７‐Up to the present Successive Deans of the Institute Organizational Chart

Collaboration research

　　The institute has conducted research in the field of tropical medicine for the past ６０ years since its establishment in １９４２． The institute was reorganized to make extensive collaboration with other universities and institute in the field of interdisciplinary tropical medicine with molecular biology, entomology, anthropology, social medicine, etc.
　　These activities of the institute are expected to contribute to remarkable progress of tropical medicine.
　　The senior staff composed of professors of the institute and the executive committee make plans for research work. The steering committee and the collaboration professional committee composed of experienced scientists coordinate the various collaboration researchs. Institute of Tropical Medicine Steering Committee The University of Tokyo

　Professor Emeritus　　Manabu Sassa　　　　　

National Institute of Infectious
Diseases

Honorary Post　　Akira Oya　　　　　　　

Nagasaki University

Professor Emeritus　　Keizo Matsumoto　　　　

The Institute of Medical Science
The University of Tokyo

Director　　Ken‐ichi Arai　　　　　

Research Institute for Microbial
Diseases Osaka University

Director　　Yoshitake Nishimune　　

The International Medical Center

President　　Yoshio Yazaki　　　　　

National Institute of Infectious
Diseases

Director　　Yoshifumi Takeda　　　

Japan International Cooporation
of Welfare Services

Senior Medical Adviser　　Takashi Wagatsuma　　　

Kobe University

Professor　　Shigeaki Sato　　　　　

Nagasaki University

Professor　　Keiji Ide　　　　　　　　

Dean　　Hiroshi Saitou　　　　　

Dean　　◎Akira Igarashi　　　　　

〃　　　　　　　　Professor　　Toshiya Hirayama
〃　　　　　　　　Professor　　Hiroji Kanbara
〃　　　　　　　　Professor　　Yoshiki Aoki
〃　　　　　　　　Professor　　Michio Nakamura
〃　　　　　　　　Professor　　Hideyo Itakura
〃　　　　　　　　Professor　　Tsuyoshi Nagatake
〃　　　　　　　　Professor　　Naoki Yamamoto
〃　　　　　　　　Professor　　Masahiro Takagi
〃　　　　　　　　Professor　　Tsutomu Mizota
〃　　　　　　　　Professor　　Masaki Shimada

◎：Chairman

Collaboration Research Sytem


		Steering Committee
The senior staff （Professors）


		Collaboration professional committee



		Executive committee

understanding of the health problems in tropics, to increase their ability to cope with them, and to give a fuller knowledge of the cultures and the life of the people in tropics.
　　Physicians and professionally qualified persons working in health and related fields may apply for admission to the course. Fifteen candidates are accepted to the course in a year. The course consists of １３ weeks （June‐August） of instruction and examination. Teaching is undertaken by the full‐time staff and guest lecturers.
　　The course provids lectures and laboratory and field practices in virology, bacteriology, protozoology, parasitology, medical entomology, environmental physiology, biochemistry, pathology, internal medicine, and geography and culture in tropics. Candidates who completed successfully the course are awarded the Diploma in Tropical Medicine

Institute of Tropical Medicine Collaboration Professoional Committee

Scope of Activity

　　Based upon the mission statement issued in １９９９， in the Institute of Tropical Medicine, basic and applied studies on tropical medicine are being undertaken. These studies aim at developing knowledge for diagnosis, treatment and prevention of tropical diseases focusing on infectious ones.
　　The research activities consists of three major fields; research on pathogens such as viruses, bacteria, protozoa and helminthes, research on human pathology and research on natural and social environment. Research subjects are of wide range from the bench to the latrine, from molecular biology to field surveys at grassroot level. Collaborative studies with World Health Organization, Ministry of Foreign Affairs of Japan, Japan International Cooperation Agency, foreign universities and institutions are on going.
　　The achievements attained through these activities have been published in journals inside and outside Japan as well as in the "Tropical Medicine", an official journal of the institute.

Postgraduate School

　　The Docter Course in the Institute belongs to the Postgraduate School of Medical Science in Nagasaki University. Students who want to study in the Course must pass the entrance examinatoin of the School and thereafter can select the special subject listed by each professor in the Institute. The number of the student in ２０００ is ３１（including foreign students）.

Three‐month Course on Tropical
Medicine and Related Studies

　　The course aims to provide participating persons with a better . Gunma University Professor Mamoru Suzuki
Kyusyu University 　Professor Emeritus Isao Tada
Kobe University Professor Haku Hotta
Kumamoto University Professor Hiroshi Maeda
University of the Ryukyus Professor Shigeo Nonaka
Oita Medical College Professor Kumato Mifune
Miyazaki Medical College Professor Youichi Minamishima
University of Occupational and
Environmental Health Professor Takekiyo Yoshimura
Osaka International University Professor Yuji Yamamoto
Keio University Professor Yoshiyasu Takefuji

Nagasaki University

School of Medicine Professor Taiichirou Takemoto

　　　〃　　 Professor Shigeru Katamine

School of Pharmaceutical Sciences Professor Nobuyuki Kobayashi

Institute of Tropical Medicine Professor　 ◎Hideyo Itakura

　　　　　　〃　　 Professor Akira Igarashi

　　　　　　〃　　 Professor Toshiya Hirayama

　　　　　　〃　　 Professor Hiroji Kanbara

　　　　　　〃　　 Professor Yoshiki Aoki

　　　　　　〃　　 Professor Michio Nakamura

　　　　　　〃　　 Professor Tsuyoshi Nagatake

　　　　　　〃　　 Professor Naoki Yamamoto

　　　　　　〃　　 Professor Masahiro Takagi

　　　　　　〃　　 Professor Tsutomu Mizota

　　　　　　〃　　 Professor Masaaki Shimada

　　　　　　〃　　 Assistant

　　　　　　　　　 Professor Nobu Oowatari

◎：Chairman

Adomission ceremony in １９９９

Training Course in Research
of Tropical Medicine

　　Arrangements for conducting the course in this Institute are administered by Japan International Cooperation Agency, commissioned by the Government of Japan to execute Technical Cooperation Programs from １９８３．　　This course is conducted by the Government of Japan as a part of its Technical Cooperation Programs for developing countries with a view of contributing to upgrading their standards in tropical medicine and to promoting friendly relations to the countries.
　　The purpose of this course is to help the control of endemic and epidemic diseases infesting the Torrid Zone. Through the guidance of the staff of the Institute, the participants will enrich their fundamental knowledge and practical techniques for various medical problems in the tropics.
　　Individual participants will study on a selected subject in the responsible department for a year. Capacity of each department is normally limited to one person.

Public Lectures
at the Institute

　　The Institute of Tropical Medicine has public lectures for citizens annually. The lectures address issues pertaining to travellers on tropical diseases. It is intended to prepare the public to maintain good health abroad. The other aim is to open our intellect and knowledge to the public.

Publications

Tropical Medicine
　　This is the quarterly journal that publishes the original articles from this institute. The journal was first published in March，１９５９ as “Endemic Diseases Bulletin of Nagasaki University”. In １９６７， the name was changed to “Tropical Medicine”.

Institute of Tropical Medicine,
Nagasaki University
　　The first English guide for foreign visitors was printed in １９７１． The revised adition is published every year.

Department of Virology

　　This Department has been conducting basic and applied research on mosquito‐borne flaviviral diseases such as Japanese encephalitis （JE）, dengue fever （DF）/dengue hemorrhagic fever （DHF）, as well as hepatitis C.
Outbreak investigations on mosquito‐borne flaviviral diseases
　　Requested by Japan International Cooperation Agency（JICA）, outbreak investigation was conducted on the acute encephalitis which was caused by Nipah virus in Malaysia from September １９９８ to March １９９９． Another investigation was carried out, requested by the Ministry of Health and Welfare, on the West Nile virus encephalitis occurred in New York during the summer in １９９９．
Analysis on the structure and function of JE and dengue viral genome
　　Nucleotide sequence analysis and molecular expression of JE and dengue viral genome have been carried out together with long PCR techniques in order to study molecular epidemiology, epitope analysis, biological activity of nonstructural proteins, and virulent viral gene responsible for viral pathogenesis.
Development of rapid diagnosis on flaviviral diseases
　　Viral genome detection and identification by PCR, preparation of diagnostic antigen
from infected cell culture fluid, and simplification of IgM antibody detection have been carried out.
Activities as a WHO Collaborating Centre
　By the letter from Dr. San Tae Han, fromer Director of WHO Regional Office for the Western Pacific （WPRO)　dated ２３ November １９９３， the Department of Virology, Institute of Tropical Medicine, Nagasaki University was designated as WHO Collaborating Centre for Reference and Research on Tropical Viral Diseases. On ９ August １９９４， Inauguration Ceremony was held at Pompe Hall by the presence of Dr. Han and approximately １２０ guests, which was followed by the WHO Workshop“Epidemiology and Control on DF/DHF and JE”. The Department has received WHO fellows from Vietnam. Fiji, and the Philippines, dispatching WHO short‐term consultants on the subjects relevant to its terms of reference. Dr.Kouich Morita was appointed as the Regional Advisor on Infectious Diseases, WHO‐WPRO, from １６ May １９９５ to １５ May １９９８． According to the letter from Dr. Shigeru Omi, present Director of WHO‐WPRO, the designation of Virology Department as the WHO Collaborating Centre was extended to ２３ September ２００３．

Professor Akira Igarashi
Assistant professor Kouichi Morita
Research Associate Futoshi Hasebe
Postdoctoral Fellow （COE） Maria del Carmen Parquet
Senior Research Assistant Toshiko Ueno
Senior Research Assistant Mutsumi Nagata
Technician Kazumi Jodai
Postgraduate student Afjal Hossain Khan
Postgraduate student Shu Ko‐ha
Postgraduate student Edward Gitau Mathenge
Rompaku Fellow Paresh Sumatilal Shah Adomission ceremony in １９９９ Laboratory of recombinant DNA experiments
（P２‐level） WHO Workshop

Department of Bacteriology

　　Our major research interest is to elucidate the etiologic agents isolated from pathogenic bacteria related to the worldwide emerging and re‐emerging diseases.
Studies on the cellular and molecular mechanisms of diarrhea induced by bacterial enterotoxins:
　　Aeromonas sobria hemolysin is important in the pathogenesis of diarrhea caused by this enteropathogenic bacterium. By immunoprecipitation analysis using hemolysin and anti‐hemolysin antibody, a ６６‐kDa protein （p６６） was identified as a receptor for A. sobria hemolysin on Intestine ４０７ cells. The p６６ was found to be a glycosylphosphatidylinositol‐anchored glycoprotein expressed on the surface of Intestine ４０７ cells. （Ref. Microb. Pathog. （１９９９）２７：２１５）
　　Focusing on the molecular mechanisms of the diarrhea induced by heat‐stable enterotoxins （STd） of enteropathogenic bacteria, we are also studying １）interaction of Escherichia coli heat‐stable enterotoxin with its receptor and ２）activation of guanylate cyclase（GC‐C）by STa.（Ref. Eur. J. Biochem．（１９９９）２６３：３３８）
Studies on the pathogenesis of Helicobacter pylori:
　　To investigate a potential mechanism of how H. pylori establishes infection, we investigates the host‐parasite relationships of H. pylori, focusing on vacuolating cytotoxin A （VacA）and Cag pathogenicity island （Cag PAI）.
　　１）VacA exposed to alkaline or acid conditions, with subsequent neutralization, exhibits enhanced vacuolating activity;the acid or alkali‐activated VacA appears to bind a cell surface receptor protein of ～２５０kDa. N‐terminal and internal amino acid sequence is consistent with the hypothesis that p２５０ is RPTPβ. Phorbolmyristate （PMA, TPA） induces differentiation of the human leukemic cell line HL‐６０ into cells with macrophage‐like characteristics and enhances the susceptibility of HL‐６０ cells to VacA. PMA induced expression of RPTPβmRNA and protein as determined by RT‐PCR and indirect immunofluorescence studies. Vitamin D３ and IFN‐γ, which stimulate defferentiation of HL‐６０ cells into a monocyte‐like cells, also induced VacA sensitivity and expression of RPTPβ mRNA, whereas １．２％ DMSO and retinoic acid, which stimulated the maturation of HL‐６０ into granulocyte‐like cells did not. RPTPβ anti‐sense oligonucleotide inhibited induction of VacA sensitivity and expression of RPTPβ. Double immunostaining studies also indicated that newly expressed RPTPβ colocalized with VacA in PMA‐treated HL‐６０ cells. BKN‐２１ cells transfected with the RPTPβ cDNA acquired VacA sensitivity. All data are consistent with the conclusion that acquisition of VacA sensitivity by PMA‐treated HL‐６０ cells results from induction of RPTPβ, a protein that function as the VacA receptor. (Ref. J. Biol. Chem.（１９９９）２７４：３６６９３，J. Biol.Chem.（２０００）２７５：１５２００）
　　２）Human β‐defensin‐２（hBD‐２）is an antimicrobial peptide which belongs to one of the most important host defence system against bacterial infection in several epithelial tissues. We studied the effect of H. pylori on the expression of hBD‐２ mRNA in MKE４５ gastric mucosal cells. H. pylori, but not culture filtrate, increased hBD‐２mRNAlevel in MKN４５ cells, whereas thus inductive effect of H. pylori was not detected when Intestine４０７ cells were incubated with H. pylori. Among the tested strains of H. pylori, which lacks Cag PAI, did not induce hBD‐２ mRNA in MKN４５ cells. These results suggested that cag PAI of H. pylori is important for inductive expression of hBD‐２ mRNA in MKN４５ cells. Exposure of MKN４５ cells to Salmonella typhimurium, S. enteritidis, S. typhi, and S. dublin, but not Escherichia coli ML３５， resulted in remarkable induction of hBD‐２ mRNA.（Ref. Biochem. Biophys. Res. Commun.（１９９９）２８３：７７０，Infect.Immun.（２０００）６８：１８０６）
Studies on the development of cholera vaccine.
　　The overexpression of fimbriae of Vibrio cholerae O１ is uuder study for use in cholera vaccine trial. （Ref. Microbiol. Immunol.（２０００）４４：４３９）

Professor Toshiya Hirayama

Assistant professor Yoshio Ichinose

Research Associate Masahiko Ehara

Research Associate Akihiro Wada

Technologist Mamoru Iwami

Technician Kayo Honda

Postgraduate Student Takahiro Kimura

Research Associate Akitoyo Ichinose

Department of Protozoology

　　Our main purpose is to clarify infection mechanisms of intracellular protozoan parasites.

Study of malaria parasites
１）Specific immune reaction in malaria.
２）Surviving strategies of Plamodium falciparum in mammalian hosts.
３）Epidemiology of human malaria.

Study of trypanosomes
１）Functions and expression mechanism of transsialidase.
２）Adaptation mechanisms of Trypanosoma species to environments.
３）Modification of infected host‐cells by Trypanosoma cruzi.
４）Simple diagnostic methods for Chagas' disease in endemic fields.
Other studies
１）Molecular epidemiology of pathogenic strains of Entamoeba histolytica in the Philippines.
２）Epidemiology of cryptosporidiosis

Professor Hiroji Kanbara
Assistant Professor Haruki Uemura
Research Associate Tetsuo Yanagi
Research Associate Shusuke Nakazawa
Technician Miki Kinoshita
Technician Kurenai Matsuo
Postgraduate Student Mie Kato
Postgraduate Student Katsunori Shinohara
Postgraduate Student Ton That Ai Long
Postgraduate Student Chaturong Putaporntip
Postgraduate Student Mohammed Nasir Shuaibu
Postgraduate Student Maria Cecilia Huaman
Postgraduate Student Toshio Miyazaki Laboratory for culture Plasmodia sporozoites from ruptured oocysts in
Anopheline mosquito Amastigotes（left）and trypomastigotes（right）of
Trypanosoma cruzi Cytotoxicity of VacA toxin through its binding to receptor‐protein tyrosine phosphataseβ Laboratory

Department of Parasitology

　　The research activities are concentrated on filariasis and schistosomiasis which constitute the major public health problems in the tropics.
Filariasis
　　Brugia malayi（Cheju strain, periodic form）, B. pahangi and the vector mosquito, Aedes aegypti (Liverpool strain）have been maintained in the laboratory for many years. Highlights of recent studies are as follows.
１）Mode of action of diethylcarbamazine （DEC） :
　　Recently we reported that DEC is a competitive inhibitor of acetylcholinesterase of filarial worms, DEC inhibits cell proliferation, disrupts the microtubules of LLC‐MK２ cells, inhibits polymerization of microtubules and disrupts the pre‐formed microtubles in vitro.
２）Development of a simple and sensitive method for determination of serum concentration of ivermectin （IVM）and DEC:
　　IVM and DEC modified partially in their chemical structure successfully produced the antibody against drugs. Therefore the serum concentration　（５ ng/ml）of IVM and DEC can be determined by EIA.
３）Combination of DEC and IVM for the treatment of filariasis:
　　Several lines of evidence indicate that DEC and IVM interact additively or synergistically against microfilariae and adult worms of B. pahangi in vivo and in vitro.
４）Screening of antifilarial drugs from medical plants:
　　Vernonia amygdalina from Africa, Neurolaena lobata from Guatemala and Cardiospermun halicacabum from Thailand were effective in vitro on B. pahangi adult worms and microfilariae.
５）Epidemiology and control of bancroftian filariasis:
　　A research project was carried in Kwale, Kenya, in cooperation with Kenya Medical Research Institute（KEMRI）during the period of １９９０ and １９９６．Transmission potential and morbidity were studied. Mass‐chemotherapy with combination of DEC and NaHCO_３ was evalualed.
Schistosimoasis
　　Schistosoma mansoni（Puerto Rican strain and Kenyan strain）, S. haematobium （Kenyan strain）and some strain of vector snails have been maintained in the laboratory. Highlights of recent studies are as follows.
１）Swimming behavior of miracidia:
　　cAMP is involved in the control of ciliary beating and chemotaxis of miracidia.
２）Mechanisms of penetration of cercariae into skin:
　　The studies suggest the involvement of protein kinase C in proteolytic enzyme release from cercariae.
３）Epidemiology and control of S. haematobium infection:
　　Since １９８１， the research project on Schistosomiasis haematobia was carried out in Kwale, Kenya, in cooperation with KEMRI for １５ years. The highlights of our studies are human water contact study, cercarial concentration in natural water, ecology of Bulinus globosus, usefulness of urinary reagent strips, new immunodiagnostic test（urine ELISA, modified COPT）, effect of piped water supply, KAP study（knowledge, attitute and practices）, health education, morbidity studies using ultrasound and environmental modification for snail control.
Recently high prevalence of bladder cancer and liver fibrosis is reported in the community.

Professor Yoshiki Aoki

Assistant Professor Yasunori Fujimaki

Research Associate　　 Kanji Watanabe

Technologist Mitsumasa Miura

Technician Nami Fujii

Postgraduate Student Tomoharu Ohki

Postgraduate Student Hidehiko Yamauchi

Postgraduate Student Hiroshi Matsuyama

Postgraduate Student Gunawardena Nipul Kithsiri

Postgraduate Student Teruyo Kusaba

Department of

Thermal Adaptation

　　Study on the adaptation mechanisms to the hot tropical environment in human beings and animals and its application of tropical medicine are the aims in the Department, which was newly established in　１９９４． In collaboration with the Department of Environmental Physiology, the following researches are on going.
Study on long‐term heat acclimatization in tropical inhabitants
　　Core temperature, skin temperatures, local sweat rates, and metabolic rate during heat load or exercise and Ach sensitivity of the sweat gland are compared between Japanese and tropical inhabitants （Thai and Africans）. It has been revealed that in a hot environment, tropical inhabitants can efficiently regulate their body temperature with less amount of sweat compared to Japanese, because of their excellent dry heat loss ability（conduction, convection and radiation） and suppression of ineffective sweating which drips off the skin. Suppressed sweating in tropical residents is attributed to adaptation in both central（upward shift of threshold core temperature for sweating and suppression of the gain）and peripheral（suppression of Ach sensitivity of the sweat gland）sudomotor mechanisms. This stucy is carried out in collaboration with the Department of Physiology, Chiang Mai University, Thailand.
Study on cross‐adaptation of physical training to heat
　　After a short‐term physical training, heat tolerance is enhanced by the activated sweat response. On the other hand, the athletes who trained for a long time are tolerant to heat, as their sweat response is suppressed. The roles of central and peripheral mechanisms are being investigated.
Study on cellular and molecular heat‐tolerance in temperature sensitive mutant cells
　　The temperature‐sensitive mutant from mouse breast cancer cells, tsFT１０１， is multinuclei when cultured at ３９℃. The induction of thermotolerance and also the induction of heat shock proteins due to pre‐heating at ４５℃ for ３０ min are very little in tsFT１０１ cells cultured at ３９℃.The mechanisms of thermotolerance in cellular and molecular level are under investigation by using this cell line.
Study on cold adaptation in the weak heattolerant animal, pika（Ochotona）
　　The pika（Ochotona）living in the cold areas or high mountains attracts attentions as an animal model of cold adaptation as well as highaltitude adaptation. Th pika is intolerant to heat for lack of efficient heat loss mechanisms, and does not hibernate in winter. To clarify the cold adaptation mechanisms in pikas, physiological studies on atonomic and behavioral thermoreguration, anatomical studies and the field studies in their natural habitats in China and Mongolia are on going.
Comparison of thermal adaptability among tropical, subtropical and temperate subjects
　　We compare the natural environmental adaptability through out the effect of environmental temperature and sunlight on functional, morphological, and organic changes in tropical（Thai）, subtropical （Nepal） and temperate（Japanese）subjects.
　Professor （concurrent）
　Research Associate Eiko kaneda Ultrasonography of the bladder of the patient infected with S. haematobium Medical plant used by traditional healer in Kenya Experiment of thermal sweating in the environmental chamber Laboratory of cell culture

Departement of Biochemistry

　　Our research interest is focused on the molecular events ocurring in inflammatory cells for the defense against invading microbes. Reactive oxygen species are essential for killing most of bacteria, fungi, and parasites. We are therefore investigating mechanisms for the expression and activation of superoxide‐degenerating NADPH oxidase system.
GATA‐３ as the Eosinophil‐specific Repressor for the Expression of gp９１^phox, an Electrontransferring Component in Phagocyte NADPH Oxidase System
　　In a systematic search for cis‐elements regulating gp９１^phox exression in eosinophil lineage, we identified an inhibitory element containing a GATA consensus site at the proximal promoter and GATA‐３ as the specific protein binding to that site. Two‐base‐pair substitution at the consensus site abolished inhibition of the promoter activity in eosinophil‐committed HL６０‐C１５ cells, indicating that the GATA‐３ binding to the site is a repressor in the cells. Because eosinophil is the only cell expressing GATA‐３ among human phagocytes and B lymphocytes, GATA‐３ is an eosinophil lineage‐specific repressor of gp９１^phox gene.
　　PU．１ but not HAF‐１ is a Common Activator for the Expression of gp９１^phox in Neutrophils, Monocytes and B Lymphocytes
　　For the expression of gp９１^phox in these cells, we previously suggested a common transcriptional activator which requires the position‐５３　based on an analysis of a novel patient with chronic granulomatous disease. HAF‐１ and PU．１ were indentified as candidates for this activator. We, therefore, examined ６０ fragments with onebase substitutions neighboring to‐５３， and found two sequences;one has a mutation at‐５６ and impairs the binding of HAF‐１，　and the other mutation at‐５０ and impairs the binding of PU．１ The‐５０ mutant promoter but not‐５６ mutant one exhibited decreased reporter activity, indicating PU．１， but not HAF‐１， to be an essential activator for the expression of the gene in those cells （Fig．１）．A discovery of a similar patient with a point mutation at‐５２ which abolished the binding of PU．１ confirmed our conclusion.
　　Our future aim is to apply these findings to in innovation of techniques to control tropical diseases and allergy.

Professor Michio Nakamura

Assistant Professor Atsushi Kumatori

Research Associate Shoichi Suzuki

Technologist Toshiyuki Moriuchi

Postgraduate Student Hao Li Jun

Postgraduate Student MD. Rafiqul Islam

Postgraduate Student Maki Takata

Postgraduate Student K. A. Deepa

Visiting Researcher Yang Tan

Department of Pathology

　　Research projects are fundamentally geopathological and histopathological investigation of tropical diseases in collaboration with other overseas or domestic institutions.
　　The pathology department is responsible for postmortem examinations and histological diagnostic pathology of surgical speciments including special research work on liver biopsy at the Nagasaki University Hospital.
　　In addition to the routine services mentioned above, the department is also responsible for lectures and practice for the undergraduate students at Nagasaki University School of Medicine on pathology of the hematopoietic system, liver, gallbaldder, biliary ducts and pancreas.
　　The postgraduate course of ordinary pathology, tropical pathology and liver pathology for graduate students of medicine is a four‐year program leading to Ph. D.
　　The five‐year professional pathologist program is offered, leading to the qualified pathologist of the Japanese Society of Pathology.
　　Facilities consist of histology, immunopathology and molecular pathology laboratories, and electron microscopy.
Present research projects are as follows:
１．Pathology of tropical diseases including infections, neoplasms, and other diseases.
２．Liver diseases in the tropics such as viral hepatitis, cirrhosis of the liver, hepatocellular carcinoma, and other endemic diseases.
３．Geopathology, histopathology and molecular pathology of Kaposi's sarcoma
４．Geopathology of tumors and viral oncogenes in East Africa.
５．Geopathology of tumors in South‐east Asia.
６．Interdisciplinary study on environmental pathology in the tropics: environmental factors, human ecology and disease manifestations.

Professor Hideyo Itakura

Associate Professor Kan Toriyama

Research Associate Masachika Senba

Research Sssociate Masachika Iseki

Technician Akemi Arao Fig．１． Reporter gene expression driven by various mutant gp９１^phox promoters Laboratory of microtome Histology slide conference

Department of Internal Medicine

　　Our main studies are described in the followings.

．Comparative study on respiratory infections between Thailand and Japan
　　Our department has promoted collaboration study on respiratory infections with Chaing Mai University in Thailand. Since then the pathogens of respiratory infections has been recognized. As a result the antimicrobial treatment has been appropriately modified.

．The laboratory and clinical studies on bacterial respiratory infections

．Studies on anti‐inflammatory mediator therapy in chronic respiratory infections
　　Our studies have revealed that the neutrophil activator, IL‐８ and neutrophil elastase, play a very important role in chronic respiratory infections. The studies for anti‐mediator therapies are undergoing.

．Basic and clinical studies on nosocomial infections by Staphylococcus aureus
　　Staphylococcal infection is one of the serious problems of nosocomial infections. We established a method for the management of nosocomial infections. Although we could reduce the occurrence of MRSA infections, there are various problems concerning this organisms particularly its pathogenecity.

．Analysis of the normal nasal and oropharyngeal flora in children and pediatric patients with upper respiratory infections

．Rapid diagnonsis by molecular biological technique （PCR）
　　Using PCR（Polymerase Chain Reaction）technique, it is possible to detect the pathogens rapidly even if a few number of pathogens are present in clinical specimens. We are using the PCR for the diagnosis of mycobacterial infections and obtaining satisfactory results.

．Collaboration study in Uganda on the treatment of AIDS patients with infections（tuberculosis, cryptococcal meningitis and e.t.c）
　　Since １９９０ we have investigated the condition of AIDS in Uganda to save patients complicated with infections. Caollaboration project has been with the School of Medicine, Makerere University, Uganda.

．Basic and clinical studies on influenza

．Chinical study on acute respiratory infections and bacterial meningitis among the children in Bangladesh

．Study on Bacterial adherence of respiratory infection.

Professor Tsuyoshi Nagatake

Associate Professor Kazunori Oishi

Research Associate Hideaki Amano

Research Associate Kiwao Watanabe

Research Fellow Kamruddin Ahmed

Postgraduate Student Kazushi Motomura

Postgraduate Student Tomoo Ukon

Postgraduate Student Yuko Yamaguchi

Postgraduate Student Mariko Saito

Postgraduate Student Junko Goto

Department of Preventive
Medicine and AIDS Research

　　This department was newly added to the institute in １９７８ as a research division open to visiting professors from other universities and institutes. It is run by concurrent research staff for the present. We have planned and started from January of １９９７ a series of fundamental research to answer the question how and what mechanisms retroviral infection may lead to several diseases including acquired immunodeficiency syndrome（AIDS）and adult T‐cell leukemia （ATL）.
Study on the mechanism of transactivation of several cellular genes by HTLV‐I‐Tax and HIV‐Tat
　　HTLV‐I and HIV are known to be causative agents for ATL and AIDS, respectively. HTLV‐I‐Tax and HIV‐Tat are nuclear proteins which transcriptionally trans activate not only their own enhancers in the long terminal repeat but also a number of cellular genes. We have previously demonstrated the capacity of the Tax of HTLV‐I to modulate the expression of various cellular genes: the cytokine genes for IL‐１α, IL‐６， IL‐８， IL‐１０， and the cell adhesion molecule gene for ICAM‐１． We are now intending to study the mechanisms of transactivation of cellular genes including IL‐８， IL‐１０， ICAM‐１， and iNOS by Tax or Tat.
Study on the mechanism of Tax independent NF‐κB activation
　　HTLV‐I‐infected cells have been shown to have high levels of active NF‐κB and Tax has been demonstrated to active some cellular genes by causing an increase in HF‐κB levels. However, in the ATL samples, viral mRAN are not detected. These results indicate that the celluar genes are constitutively overexpressed in the absence of Tax in vivo. These findings imply that there is another mechanism independent of Tax underlying the NF‐κB activation in fresh ATL cells. The mechanism of Tax independent NF‐κB activation is under investigation by using TL‐Oml cells.
Study on mechanism of apotosis induction in HIV or HTVL‐I infection
　　Generally, the length of time between HIV infection and development of AIDS is considered to be　１０ years on average. HIV infection is accompanied by the progressive loss of CD４ Tcells. Apoptosis, a form of programmed cell death, has been implicated in pathogenicity related to infection with HIV. HTLV‐I Tax also leads to apoptotic cell death. Apoptotic pathway and its mechanism which account for the pathophysiology in HIV or HTLV‐I infected individuals are under investigation by using Tcells transfected to constitutively express Tat or Tax.

　Visiting Professor Naoki Yamamoto
　Visiting Associate Professor Takao Masuda
　Research Associate Naoki Mori
　Technician Masako Sasaki Laboratory Laboratory Laboratory for biochemical research Tissue culture room


Department of Medical Entomology 　　Main interest in the department is analysis of environmental factors that affect the trasmission of insect‐borne diseases, and pursuing better vector control strategy that is harmonious to the environment. １．Physiology and ecology of malaria vectors 　　A long‐term monitoring on main vectors of malaria has been conducted at several fields in Southeast Asian countries. Spatial and temporal changes in larval habitats, vegetation, and the impact of human activity on the environment are evaluated in relation to abundance of vectors, host preference, and other population parameters. The GIS/RS is introduced as a new tool to analyze the environment. Geographical strains of several Anopheles are comparatively studied by morphological, physiological, and genetic approach. ２．Ecology and control of dengue vectors 　　Epidemiological studies have been conducted at several fields in Southeast Asian countries. Monitoring by oviposition traps and mark‐release‐recapture experiment are performed to establish more realistic larval indices. In the laboratory Aedes aegypti and Ae. albopictus are studied on their ecological characters among gegraphical strains. Feeding behavior and population dynamics of these mosquitoes also are studied in the laboratory and fields. ３．Vector control technique related studies 　　Basic study of copepods as hopeful biological control agent against vector mosquito larvae. Biochemical approach to insecticide registance in vector mosquitoes. Professor Masahiro Takagi Assistant Professor Yoshio Tsuda Research Associate Nobuko Tuno Technician Emiko Urakawa Postgraduate Student Yukiko Higa Postgraduate Student Ronald Enrique Marales Postgraduate Student Hamady Dieng Postgraduate Student Tomomitsu Sato Postgraduate Student Maiko Hasegawa Roupaku Student Wannapa Suwonkerd Stereomicroscopic observation of mosquitoes Ramp traps for collecting mosquitoes

Preface

Historical Review

Collaboration research

Scope of Activity

Postgraduate School

Three‐month Course on Tropical Medicine and Related Studies

Training Course in Research of Tropical Medicine

Public Lectures at the Institute