Faculty Profiles - HATABU Toshimitsu

Potent plasmodicidal activity of a heat-induced reformulation of deoxycholate-amphotericin B (Fungizone) against Plasmodium falciparum. Reviewed International journal

Toshimitsu Hatabu, Tsuyoshi Takada, Nao Taguchi, Mamoru Suzuki, Kumiko Sato, Shigeyuki Kano

Antimicrobial agents and chemotherapy 49 ( 2 ) 493 - 6 2005.2

Language：English Publisher：AMER SOC MICROBIOLOGY

The emergence and spread of drug-resistant Plasmodium falciparum continue to pose problems in malaria chemotherapy. Therefore, it is necessary to identify new antimalarial drugs and therapeutic strategies. In the present study, the activity of a heat-treated form of amphotericin B (HT-AMB) against P. falciparum was evaluated. The efficacy and toxicity of HT-AMB were also compared with those of the standard formulation (AMB). HT-AMB showed significant activity against a chloroquine-resistant strain (strain K-1) and a chloroquine-susceptible strain (strain FCR-3) in vitro. The 50% inhibitory concentrations of HT-AMB were 0.32 +/- 0.03 mug/ml for strain K-1 and 0.33 +/- 0.03 mug/ml for strain FCR-3. In the presence of 1.0 mug of HT-AMB per ml, only pyknotic parasites were observed after 24 h of incubation of early trophozoites (ring forms). However, when late trophozoites and schizonts were cultured with 1.0 mug of HT-AMB per ml, those forms multiplied to ring forms but the number of infected erythrocytes did not increase. These results indicate that HT-AMB possesses potent antiplasmodial activity and that the drug is more effective against the ring-form stage than against the late trophozoite and schizont stages. HT-AMB was observed to have little cytotoxic effect against a human liver cell line (Chang liver cells). In conclusion, the results suggest that HT-AMB has promising properties and merits further in vivo investigations as a treatment for falciparum malaria.

DOI： 10.1128/AAC.49.2.493-496.2005

群馬県における成人のスギ花粉およびダニIgE抗体保有率 10年間における変化および自覚症状との関連について

A study of chloroquine resistance of Plasmodium falciparum using the in-vitro sensitivity test and polymerase chain reaction (PCR).

HATABU, TOSHIMITSU

Acta Medica Philippina 39(2): 7-10 2005

比田井裕子, 畑生俊光, 荒木忠晴, 佐藤久美子, 嶋田淳子

北関東医学雑誌 Vol.55 307 ( 3 ) 307 - 307 2005

群馬県におけるToxoplasma gondii抗体保有率の推移

川島悟美, 畑生俊光, 佐藤久美子, 狩野繁之, 嶋田淳子

北関東医学会誌 Vol55 307 ( 3 ) 307 - 307 2005

In vitro susceptibility and genetic variations for chloroquine and mefloquine in Plasmodium falciparum isolates from Thai-Myanmar border

HATABU, TOSHIMITSU

Southeast Asian J Trop Med Public Health Vol 36 suppl 4: 73-78 2005

A study of chloroquine resistance of Plasmodium falciparum using the in-vitro sensitivity test and polymerase chain reaction (PCR).

HATABU, TOSHIMITSU

Acta Medica Philippina 39(2): 7-10 2005

A Pilot Field Survey on the in Vitro Drug Susceptibility of Plasmodium Falciparum in Lao PDR

Toshimitsu Hatabu, Nao Taguchi, Shigeyuki Kano, Viengxay Vanisaveth, Samlane Phompida, Jun Kobayashi, M. Kaiissar Mannoor, Hiromu Toma, Hisami Watanabe

Tropical Medicine and Health 33 ( 2 ) 103 - 104 2005

In vitro susceptibility and genetic variations for chloroquine and mefloquine in Plasmodium falciparum isolates from Thai-Myanmar border. Reviewed International journal

Toshimitsu Hatabu, Shin-ichiro Kawazu, Somei Kojima, Kumiko Sato, Pratap Singhasivanon, Sornchai Looareesuwan, Shigeyuki Kano

The Southeast Asian journal of tropical medicine and public health 36 Suppl 4 73 - 9 2005

Language：English

In vitro drug susceptibility to chloroquine (CQ) and mefloquine (MF) were assessed in 39 P. falciparum isolates from the Thai-Myanmar border area. To further characterize CQ- and MF-resistance profiles in this area, we also analyzed pfcrt K76T mutation that is critical for CQ resistance, and pfmdr1 polymorphism that has an association with MF resistance. Eighteen isolates were successfully examined by in vitro tests for CQ, and 17 of them had resistance to the drug. Geometric mean concentration of CQ that inhibited the growth of parasites at 50% (IC50) was 371 +/- 227 nM (105-971 nM). Sixteen isolates were successfully examined by in vitro tests for MF, and 8 of them were resistant to the drug. Geometric mean of IC50 for MF was 41 +/- 31 nM (4-125 nM). Genotypes of drug resistance, such as pfcrt and pfmdr1 mutations, were also analyzed. All the 39 isolates had the same haplotype (CVIET) for PfCRT at its 72-76th amino acids. A pfmdr1 Y86 mutation was found in 95% of isolates. A pfmdr1 D1042 mutation was also present in 7 isolates, while no pfmdr1 Y1246 mutation was observed. These results indicated a correlation between CQ resistance and the pfcrt T76 and pfmdr1 Y86 mutations.

Plasmodium falciparum: selenium-induced cytotoxicity to P-falciparum

N Taguchi, T Hatabu, H Yamaguchi, M Suzuki, K Sato, S Kano

EXPERIMENTAL PARASITOLOGY 106 ( 1-2 ) 50 - 55 2004.1

Language：English Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE

The in vitro antimalarial activity of sodium selenite (NaSe) was investigated and the mechanism of its action was studied. NaSe had antimalarial activity against both the chloroquine-susceptible strain FCR-3 and chloroquine-resistant strain K-I of Plasmodium falciparum. The shrunken cytoplasm of the parasite was observed in a smear 12h after treatment with NaSe. Co-treatment with copper sulfate (CuSO4) in culture did not affect the antimalarial activity of NaSe, but NaSe cytotoxicity against the mammalian cell line Alexander was decreased significantly. The intracellular reduced glutathione level of parasitized red blood cells was decreased significantly by treatment with NaSe, and the decrease was consistent with their mortality. Treatment with NaSe had a strong inhibitory effect on plasmodial development, and NaSe cytotoxicity to human cells was decreased by co-treatment with CuSO4. These results suggest that co-treatment with NaSe and CuSO4 may be useful as a new antimalarial therapy. (C) 2004 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.exppara.2004.01.005

野外調査地における熱帯熱マラリア in vitro 薬剤感受性試験の応用ーラオス人民民主共和国におけるマラリア疫学調査ー

畑生俊光

熱帯第37巻221-225 ( 221-292 ) 221 - 225 2004

A Pilot Field Trial of an in Vitro Drug Susceptibility Test Using the Anaeropack® Malaria Culture System on the Thai-Myanmar Border

Toshimitsu Hatabu, Shin-Ichiro Kawazu, Somei Kojima, Pratap Singhasivanon, Srivicha Krudsood, Sornchai Looareesuwan, Shigeyuki Kano

Tropical Medicine and Health 32 ( 4 ) 335 - 337 2004

Language：English

The AnaeroPack® malaria culture system with a portable thermostat incubator was evaluated in a field laboratory on the Thai-Myanmar border conducting in vitro drug susceptibility tests on blood samples from 5 Karen children infected with P. falciparum. Only one isolate was susceptible to chloroquine
the others were highly resistant. The IC60 value of an isolate was only resistant to mefloquine, whereas the values of the 3 patients who presumably showed recrudescence were slightly elevated in the susceptible ranges. These results suggested that chloroquine should no longer be used for P. falciparum malaria in this geographic area, and that mefloquine should be carefully monitored for its in vivo effectiveness. In this study, the AnaeroPack® malaria culture system with portable thermostatic incubator is a powerful and useful mobile tool, which aids in providing detailed evidence-based distribution data concerning of drug resistant malaria in the field. © 2004, Japanese Society of Tropical Medicine. All rights reserved.

DOI： 10.2149/tmh.32.335

Scopus

生薬由来成分による抗マラリア効果の検討

石原亜矢, 畑生俊光, 奥浩之, 鈴木守, 佐藤久美子

日本寄生虫学会大会プログラム・抄録集 73rd 2004

Binding of Plasmodium falciparum-infected erythrocytes to the membrane-bound form of Fractalkine/CX3CL1. Reviewed International journal

Toshimitsu Hatabu, Shin-Ichiro Kawazu, Masamichi Aikawa, Shigeyuki Kano

Proceedings of the National Academy of Sciences of the United States of America 100 ( 26 ) 15942 - 6 2003.12

Language：English Publisher：NATL ACAD SCIENCES

Plasmodium falciparum-infected erythrocytes (pRBCs) adhere to the endothelium via receptors expressed on the surface of vascular endothelial cells (EC) and sequester in the microvasculature of several organs and block the blood circulation. The sequestration, which involves receptors, may be related to the severity of malaria. Here, we report that pRBCs bind to the membrane-bound form of Fractalkine/CX3CL1 (FKN), which is expressed on the surface of vascular EC in various organs. pRBCs adhered to FKN on the surface of FKN cDNA-transfected Chinese hamster ovary cells (CHO-FKN cells). Both the recombinant human FKN-chemokine domain (FKN-CD) and anti-FKN-CD antibody efficiently blocked adherence of pRBCs to CHO-FKN cells. Similar to binding between FKN and FKN receptor on blood mononuclear cells, two amino acid residues, Lys-7 and Arg-47 within FKN-CD, were critical for FKN-pRBC binding. Immunohistological analysis revealed the expression of FKN on EC at the site of sequestration in the brain of a patient with cerebral malaria. These results suggest that the membrane-bound form of FKN acts as a receptor for pRBCs, and this may contribute to furthering our present understanding of cytoadherence in the pathology of falciparum malaria.

DOI： 10.1073/pnas.2534560100

Binding of Plasmodium falciparum-infected erythrocytes to the membrane-bound form of fractalkine/CX(3)CL1

T Hatabu, S Kawazu, M Aikawa, S Kano

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 100 ( 26 ) 15942 - 15946 2003.12

Language：English Publisher：NATL ACAD SCIENCES

Plasmodium falciparum-infected erythrocytes (pRBCs) adhere to the endothelium via receptors expressed on the surface of vascular endothelial cells (EC) and sequester in the microvasculature of several organs and block the blood circulation. The sequestration, which involves receptors, may be related to the severity of malaria. Here, we report that pRBCs bind to the membrane-bound form of Fractalkine/ CX(3)CL1 (FKN), which is expressed on the surface of vascular EC in various organs. pRBCs adhered to FKN on the surface of FKN cDNA-transfected Chinese hamster ovary cells (CHO-FKN cells). Both the recombinant human FKN-chemokine domain (FKN-CD) and anti-FKN-CD antibody efficiently blocked adherence of pRBCs to CHO-FKN cells. Similar to binding between FKN and FKN receptor on blood mononuclear cells, two amino acid residues, Lys-7 and Arg-47 within FKN-CD, were critical for FKN-pRBC binding. Immunohistological analysis revealed the expression of FKN on EC at the site of sequestration in the brain of a patient with cerebral malaria. These results suggest that the membrane-bound form of FKN acts as a receptor for pRBCs, and this may contribute to furthering our present understanding of cytoadherence in the pathology of falciparum malaria.

DOI： 10.1073/pnas.2534560100

In vitro susceptibility of Plasmodium falciparum isolates to chloroquine and mefloquine in southeastern Mindanao Island, the Philippines. Reviewed International journal

Toshimitsu Hatabu, Shin-ichiro Kawazu, Jun Suzuki, Reuben F Valenzuela, Elena A Villacorte, Mamoru Suzuki, Pilarita T Rivera, Shigeyuki Kano

The Southeast Asian journal of tropical medicine and public health 34 ( 3 ) 546 - 51 2003.9

Language：English

Although the presence of multi-drug-resistant falciparum malaria has been reported in the Philippines, the distribution of drug-resistant malaria parasites has not yet been determined in Mindanao Island. In vitro susceptibility of P. falciparum to both chloroquine and mefloquine was assessed to forecast the spread of drug-resistant parasites in various foci in southeastern Mindanao Island. Of the 33 isolates of P. falciparum successfully tested, 10 (30%) were susceptible, 12 (36%) showed decreased susceptibility (80 nM < or = IC50 < 114 nM), and 11 (33%) were resistant (IC50 > or = 114 nM) to chloroquine. Ten (91%) of the resistant isolates and 9 (75%) of those with decreased susceptibility were from northern and northwestern Davao del Norte Province. Chloroquine-susceptible isolates were found among patients in the eastern parts of Davao del Norte and Davao Oriental provinces. Seven isolates from several foci in the study area were all mefloquine- susceptible (IC50 < 10 nM). This is the first report indicating the potential emergence of chloroquine-resistant P. falciparum on Mindanao Island, which is presently regarded as a drug-susceptible area.

Scopus

熱帯熱マラリア原虫フィリピン・ミンダナオ島分離株におけるpfcrtおよびpfmdr‐1遺伝子多型の解析

畑生俊光, 河津信一郎, VILLACORTE E A, 佐藤久美子, RIVERA P T, 狩野繁之

日本寄生虫学会大会プログラム・抄録集 72nd 120 2003.3

タイ・ミャンマー国境地域におけるアネロパックマラリア培養システムを用いた薬剤感受性試験

畑生俊光, 狩野繁之, 小島荘明, シンハシバノン・プラタップ, ルーアリースワン・ソンチャイ

Clinical Parasitology 13 ( 1 ) 75 - 77 2003.2

Language：Japanese Publisher：日本臨床寄生虫学会

著者等が開発したアネロパックマラリア原虫培養システムの更なる野外調査地での有用性を確認するため,in vivo多剤耐性熱帯熱マラリアの流行が報告されているタイ・ミャンマー国境地域において,in vitro薬剤感受性試験を試みた.なお,培養システムには改良型冷却機能つき小型恒温槽を使用した.ラジャナガリンドラ・トロピカル・ディジーズ・インターナショナル・センター(RTIC)を来院した5名の患者より分離した熱帯熱マラリア原虫を用いた薬剤感受性試験を行ったところ,80%がクロロキン耐性であった.メフロキンについては,80%の原虫が感受性であったが,再燃を疑わせる患者3名から分離した原虫については,メフロキンに対する感受性の低下が認められた.以上の事から,アネロパックマラリア培養システムと改良携帯型恒温槽を用いたin vitro薬剤感受性試験は,従来報告されているin vivoの結果からだされている薬剤耐性マラリアの流行分布に関する疫学的考察を強化する手法として有用であると考えられた

[An imported case of falciparum malaria successfully treated with Artemether-Lumefantrine in Japan]. Reviewed

Azumi Ishizaki, Yoshiki Kikuchi, Toshimitsu Hatabu, Shigeyuki Kano, Akira Yasuoka, Shinichi Oka

Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 77 ( 1 ) 34 - 7 2003.1

Language：Japanese

Spread of multi-drug resistant malaria in the endemic areas has made malaria control more difficult. Thus, WHO recommends combination therapy for the treatment of malaria. The aim of combination therapy is to improve efficacy and to reduce the incidence of resistance development to the each component of the combination. Particularly, the combination with artemisinin derivatives shows good outcome in Thailand where high resistance for mefloquine has already been found. We report the first case of falciparum malaria, successfully treated with Artemether-Lumefantrine in Japan. Artemether-Lumefantrine is a newly developed artemisinin-based combination agent for the treatment of uncomplicated multi-drug resistant malaria. This drug has proved highly effective and well tolerated by some clinical trials abroad. This Japanese female case showed a good clinical course without any side effect.

DOI： 10.11150/kansenshogakuzasshi1970.77.34

An Imported Case of Falciparum Malaria Successfully Treated with Artemether-Lumefantrine in Japan

ISHIZAKI Azumi, KIKUCHI Yoshiki, HATABU Toshimitsu, KANO Shigeyuki, YASUOKA Akira, OKA Shinichi

Journal of the Japanese Association for Infectious Diseases 77(1):34-7 ( 1 ) 34 - 37 2003

Publisher：The Japanese Association for Infectious Diseases

DOI： 10.11150/kansenshogakuzasshi1970.77.34

CiNii Article