Updated on 2025/08/01

写真a

 
HATABU Toshimitsu
 
Organization
Faculty of Environmental, Life, Natural Science and Technology Professor
Position
Professor
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Degree

  • 博士（農学）士 ( 1999.3   東京大学 )

Research Interests

  • 細胞生物学

  • 分子疫学

  • 免疫学

  • 寄生虫学

  • 動物生理学

Research Areas

  • Life Science / Animal physiological chemistry, physiology and behavioral biology

  • Life Science / Laboratory animal science

  • Life Science / Parasitology

  • Life Science / Animal life science  / 病態生理学

Education

  • The University of Tokyo   農学生命科学研究科   応用動物科学専攻

    - 1999

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    Country： Japan

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  • The University of Tokyo    

    - 1999

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  • Okayama University    

    - 1994

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  • Okayama University   農学部   総合農業科学

    - 1994

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    Country： Japan

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Research History

  • Graduate school of Enxironmental, Life, natural Science and Technology, OKayama University   Professor

    2023.4

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  • 岡山大学学術研究院環境生命科学学域（農）   准教授

    2021.4 - 2023.3

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  • Graduate School of Environmental and Life Science, Okayama University   農学部動物生理学研究室   Associate Professor

    2012.3 - 2021.3

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  • Gunma University   School of Health Sciences Department of Laboratory Science, Faculty of Medicine   Assistant Professor

    2005.4 - 2012.3

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  • -: - 群馬大学医学部内講師

    2003

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  • -: - 群馬大学医学部助手

    2002.4 - 2005.3

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  • : 国立国際医療センター研究所 流動研究員

    1999 - 2002

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Professional Memberships

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Papers

  • γδ T cells induced by zoledronate under macrophage-depleted conditions reduce disease severity and parasite number in Eimeria tenella-infected chicks. International journal

    Quan Viet Le, Makoto Matsubayashi, Toshimitsu Hatabu

    Research in veterinary science   192   105730 - 105730   2025.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    Disease severity and local immune responses mediated by Zoledronate (ZOL)-induced γδ T cells were evaluated in chicks infected with E. tenella under macrophage-depleted conditions. Three groups of White Leghorns, including a negative control group (CT), carrageenan-treated group (CAR), and both ZOL and CAR-treated group (ZOL/CAR), were infected orally with E. tenella sporulated oocysts (1 × 104 oocysts/chick) at 14 days of age. Fecal oocyst shedding was assessed at 4-15 days post-infection. The cecum was collected for histopathological and gene expression analyses. Oocyst shedding was significantly reduced in the CAR and ZOL/CAR groups compared with the CT group (p < 0.01). The total oocyst number in the ZOL/CAR group was lower compared with those in the CAR and CT groups (p < 0.05). The lesion score and parasite burden in the CAR and ZOL/CAR groups were lower compared with those in the CT group (p < 0.01). The expression of IFN-λ, IL-17 A, and perforin mRNA in the ZOL/CAR group increased compared with that in the CAR group, whereas the expression of IFN-γ in the ZOL/CAR group decreased. The results suggest that Th1-independent immunity occurs as a local immune response induced by IL-17 A/IL-22-producing γδ T cells, which control E. tenella-induced pathology in the cecum.

    DOI： 10.1016/j.rvsc.2025.105730

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  • Evaluation of oocyst detection and PCR identification of chicken Eimeria species using intestinal contents of the rectum and cecum as different gastrointestinal tracts.

    Aruto Takano, Chie Furuya, Daikichi Morinaga, April H Wardhana, Dyah H Sawitri, Toshimitsu Hatabu, Kazumi Sasai, Hiromitsu Katoh, Makoto Matsubayashi

    The Journal of veterinary medical science   2025.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    In the present study, intestinal specimens were collected from layer chickens at poultry slaughterhouses and used to evaluate infection with Eimeria species. Intestinal contents were extracted separately from the rectum (from the duodenum to rectum) and cecum and used for analyses. Using flotation detection methods, the number of eimerian oocysts per gram was higher in the cecum than rectum. Polymerase chain reaction analysis also detected a greater abundance of Eimeria species in the cecum than the rectum. These results suggest that analysis of cecal contents could be more useful for detecting and identifying Eimeria species.

    DOI： 10.1292/jvms.25-0252

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  • Detection of Eimeria oocysts in chicken feces using flotation recovery with sucrose or saturated saline solution. International journal

    Aruto Takano, Daikichi Morinaga, Isao Teramoto, Toshimitsu Hatabu, Yasutoshi Kido, Akira Kaneko, Takeshi Hatta, Naotoshi Tsuji, Shigehiko Uni, Kazumi Sasai, Hiromitsu Katoh, Makoto Matsubayashi

    Acta parasitologica   70 ( 1 )   17 - 17   2025.1

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    PURPOSE: Flotation methods are widely used to detect oocysts/cysts of protozoans and eggs of helminths, except trematodes. However, details regarding the concentration and recovery rates of these parasites are poorly understood. METHODS: Using Eimeria tenella oocysts as a model parasite, the present study evaluated three check points: (1) the proportion of parasites that remain floating in flotation solution (sucrose or saturated saline) during centrifugation, (2) the proportion of oocysts that naturally float after addition of flotation solution after centrifugation, and (3) the rate of recovery on cover slips after completion of the flotation protocol. RESULTS: After centrifugation in sucrose solution and saturated saline solution, 82.4% and 60.3% of oocysts floated, respectively. After addition of flotation solution after the final centrifugation step, the recovery rates for oocysts that naturally floated again for 30 min in sucrose and saturated saline were 39.2% and 38.2%, respectively. The recovery rate on cover slips as the final step after performing a commonly used flotation method was 36.4% in sucrose solution (the rate for saturated saline solution could not be assessed due to rapid crystallization). CONCLUSION: Our results suggest that floating oocysts could have become dispersed by the addition of flotation solution, and not all of these oocysts remained floating after an additional 30 min of settling time although collection on cover slips could be effective for accurate recovery.

    DOI： 10.1007/s11686-024-00960-6

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  • An ultra-simplified protocol for PCR template preparation from both unsporulated and sporulated Eimeria oocysts. Reviewed International journal

    Takano A., Umali DV, Wardhana AH, Sawitri DH, Teramoto I., Hatabu T., Kido Y., Kaneko A., Sasai K., Katoh H., Matsubayashi M.

    Poult Sci.   104 ( 3 )   104810 - 104810   2025.1

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    Molecular biological techniques have enabled the accurate identification of the avian Eimeria parasite, however, the preparation of PCR template remains a bottleneck due to contaminants from feces and the robust oocyst's wall resistant to chemical and mechanical force. Generally, the preparation of PCR template involves three main steps: (1) pretreatment of oocysts; (2) disruption of oocysts; and (3) purification of genomic DNA. We prepared PCR templates from both unsporulated and sporulated E. tenella oocysts using various protocols, followed by species-specific PCR to define the limit of detection. Our data revealed that whereas neither pretreatment of oocysts with sodium hypochlorite nor purification of genomic DNA with commercial kits improved the limit of detection of PCR, disruption of oocysts was a critical step in the preparation of PCR templates. The most sensitive PCR assay was achieved with the template prepared by disrupting oocysts suspended in distilled water, followed by bead-beating and heating at 99°C for 5 min, which detected 0.16 oocysts per PCR. This ultra-simplified protocol for preparation of PCR template, which does not require expensive reagents or equipment, will significantly enhance the sensitive and efficient molecular identification of Eimeria. It will improve our understanding of the prevalence of this parasite at the species level and contribute to the development of techniques for the control in the field.

    DOI： 10.1016/j.psj.2025.104810.

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    Other Link： https://pubmed.ncbi.nlm.nih.gov/39899971/

  • Anticoccidial activity of the secondary metabolites in alpine plants frequently ingested by wild Japanese rock ptarmigans. International journal

    Asako Haraguchi, Jyunki Nagasawa, Kouji Kuramochi, Sayaka Tsuchida, Atsushi Kobayashi, Toshimitsu Hatabu, Kazumi Sasai, Hiromi Ikadai, Kazunari Ushida, Makoto Matsubayashi

    International journal for parasitology. Parasites and wildlife   25   100967 - 100967   2024.12

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    The Japanese rock ptarmigan (Lagopus muta japonica) is an herbivorous species of partridges that inhabits only alpine zones. Alpine plants are their main source of food. These alpine plants contain toxic compounds to deter herbivores from consuming them. A previous analysis of the alpine plants frequently consumed by Japanese rock ptarmigans revealed the presence of a unique mixture of secondary metabolites and a novel compound. Additionally, wild Japanese rock ptarmigans are often infected by two species of Eimeria parasites. When these parasites were experimentally administered to Svalbard rock ptarmigans (Lagopus muta hyperborean), which do not feed on alpine plants, the birds exhibited symptoms, such as diarrhea and depression, and in some cases, they died. Although little is known about the pathogenesis of these parasites in wild Japanese rock ptarmigans, it was hypothesized that compounds found in alpine plants, their main food source, may reduce the pathogenicity of Eimeria parasites. In the present study, we evaluated the anticoccidial activity of the compounds derived from alpine plants in vitro using Eimeria tenella, which infects chickens belonging to the same pheasant family, as an experimental model. Twenty-seven natural components were extracted from eight alpine plants. The natural components were added to E. tenella sporozoites and incubated for 24 h to evaluate their direct effect. Additionally, Madin-Darby bovine kidney cells were incubated with sporozoites and natural components for 24 h to evaluate the inhibitory effect of the components on sporozoite cell invasion. Six compounds from four alpine plants decreased sporozoite viability by up to 88.3%, and two compounds inhibited sporozoite invasion into the cells. Although further studies are needed to evaluate the effects of these components against Eimeria infections in vivo, our findings suggest that these alpine plants may reduce the degree of infection by decreasing the number of sporozoites in the intestinal tract.

    DOI： 10.1016/j.ijppaw.2024.100967

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  • Evaluation of the detection method by a flotation method using a wire loop for gastrointestinal parasites. International journal

    Aruto Takano, Daikichi Morinaga, Isao Teramoto, Toshimitsu Hatabu, Yasutoshi Kido, Akira Kaneko, Takeshi Hatta, Naotoshi Tsuji, Shigehiko Uni, Kazumi Sasai, Hiromitsu Katoh, Makoto Matsubayashi

    Veterinary medicine and science   10 ( 5 )   e70007   2024.9

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    Infections by gastrointestinal parasites are found in a variety of animals worldwide. For the diagnosis of such infections, the flotation method is commonly used to detect parasitic microorganisms, such as oocysts or eggs, in feces. Instead of adding a flotation solution after the final centrifugation step and using a cover slip to collect the parasites, the method using a wire loop for the recovery of the organisms has been reported as one of alternative methods. However, the recovery rates of microorganisms from the flotation method have not been analysed. In the present study, the utility of a flotation method with the use of a wire loop of 8 mm in diameter (the loop method) was evaluated using different numbers of E. tenella oocysts and Heterakis gallinarum eggs, and chicken fecal samples collected at the farms. Consequently, we found that the oocysts and eggs in tubes could be collected at a ratio of 2.00 to 3.08. Thus, our results indicate that the loop method is a simple and time saving method, implicating the application for the estimated OPG/ EPG (Oocysts/Eggs per gram) of the samples.

    DOI： 10.1002/vms3.70007

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  • Structure of putative epidermal sensory receptors in an acoel flatworm, Praesagittifera naikaiensis. International journal

    Tosuke Sakagami, Kaho Watanabe, Mayuko Hamada, Tatsuya Sakamoto, Toshimitsu Hatabu, Motonori Ando

    Cell and tissue research   395 ( 3 )   299 - 311   2024.3

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    Abstract

    Acoel flatworms possess epidermal sensory-receptor cells on their body surfaces and exhibit behavioral repertoires such as geotaxis and phototaxis. Acoel epidermal sensory receptors should be mechanical and/or chemical receptors; however, the mechanisms of their sensory reception have not been elucidated. We examined the three-dimensional relationship between epidermal sensory receptors and their innervation in an acoel flatworm, Praesagittifera naikaiensis. The distribution of the sensory receptors was different between the ventral and dorsal sides of worms. The nervous system was mainly composed of a peripheral nerve net, an anterior brain, and three pairs of longitudinal nerve cords. The nerve net was located closer to the body surface than the brain and the nerve cords. The sensory receptors have neural connections with the nerve net in the entire body of worms. We identified five homologs of polycystic kidney disease (PKD): PKD1-1, PKD1-2, PKD1-3, PKD1-4, and, PKD2, from the P. naikaiensis genome. All of these PKD genes were implied to be expressed in the epidermal sensory receptors of P. naikaiensis. PKD1-1 and PKD2 were dispersed across the entire body of worms. PKD1-2, PKD1-3, and PKD1-4 were expressed in the anterior region of worms. PKD1-4 was also expressed around the mouth opening. Our results indicated that P. naikaiensis possessed several types of epidermal sensory receptors to convert various environmental stimuli into electrical signals via the PKD channels and transmit the signals to afferent nerve and/or effector cells.

    DOI： 10.1007/s00441-024-03865-y

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    Other Link： https://link.springer.com/article/10.1007/s00441-024-03865-y/fulltext.html

  • De novo transcriptome analysis of the centrohelid Raphidocystis contractilis to identify genes involved in microtubule-based motility. International journal

    Risa Ikeda, Tosuke Sakagami, Mayuko Hamada, Tatsuya Sakamoto, Toshimitsu Hatabu, Noboru Saito, Motonori Ando

    The Journal of eukaryotic microbiology   70 ( 2 )   e12955   2023.3

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    The centrohelid heliozoan Raphidocystis contractilis has many radiating axopodia, each containing axopodial microtubules. The axopodia show rapid contraction at nearly a video rate (30 frames per second) in response to mechanical stimuli. The axopodial contraction is accompanied by cytoskeletal microtubule depolymerization, but the molecular mechanism of this phenomenon has not been elucidated. In this study, we performed de novo transcriptome sequencing of R. contractilis to identify genes involved in microtubule dynamics such as the rapid axopodial contraction. The transcriptome sequencing generated 7.15-Gbp clean reads in total, which were assembled as 31,771 unigenes. Using the obtained gene sets, we identified several microtubule-severing proteins which might be involved in the rapid axopodial contraction, and kinesin-like genes that occur gene duplication. On the other hand, some genes for microtubule motor proteins involved in the formation and motility of flagella were not found in R. contractilis, suggesting that the gene repertoire of R. contractilis reflected the morphological features of non-flagellated protists. Our transcriptome analysis provides basic information for the analysis of the molecular mechanism underlying microtubule dynamics in R. contractilis.

    DOI： 10.1111/jeu.12955

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  • Reduction of oocyte shedding and cecal inflammation by 5-aminolevulinic acid daily supplementation in laying hens infected with Eimeria tenella. International journal

    Toshimitsu Hatabu, Hung Hoang Son Pham, Wataru Aota, Shota Fujino, Rio Nishihara, Go Kawamura, Yuudai Sakogawa, Shin Taniguchi, Makoto Matsubayashi

    Animal science journal = Nihon chikusan Gakkaiho   94 ( 1 )   e13806   2023.1

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    The present study aimed to evaluate the effects of 5-aminolevulinic acid (5-ALA) on Eimeria tenella infection in laying hens. Oocyst shedding and histopathology were evaluated. A reduced oocyst shedding was observed 5 and 7 days post-infection (dpi) in the 5-ALA-administered group, but the total number of oocysts during the first infection period was not different between control and 5-ALA-treated groups. After E. tenella attack infection, the period of oocyst shedding in the 5-ALA-administered group lasted less long than that in controls. During the attack infection period, the total number of fecal oocysts in the 5-ALA-treated group was significantly lower than that in the control group. However, the parasite burden score in hens receiving 5-ALA was higher than that in controls after E. tenella attack infection. The lesion scores at 5 and 30 dpi in the control group were significantly lower than those in the 5-ALA-administered group. Therefore, 5-ALA administration might be beneficial against E. tenella infection in laying hens.

    DOI： 10.1111/asj.13806

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  • ニクロム線ループ遠心浮遊法を用いたEimeria属原虫検査法の改良と定量測定への応用

    森永 大吉, 高野 有人, 寺本 勲, 畑生 俊光, 城戸 康年, 金子 明, 笹井 和美, 加藤 宏光, 松林 誠

    日本獣医学会学術集会講演要旨集   165回   [E3P - 10]   2022.9

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    Language：Japanese   Publisher：(公社)日本獣医学会  

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  • ニクロム線ループ遠心浮遊法を用いたEimeria属原虫検査法の改良と定量測定への応用

    森永 大吉, 高野 有人, 寺本 勲, 畑生 俊光, 城戸 康年, 金子 明, 笹井 和美, 加藤 宏光, 松林 誠

    日本獣医学会学術集会講演要旨集   165回   [E3P - 10]   2022.9

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  • Differential effects of orally administered Lactobacillus acidophilus L-55 on the gene expression of cytokines and master immune switches in the ileum and spleen of laying hen with an attenuated Newcastle disease virus vaccine.

    Hung Hoang Son Pham, Yusuke Fujii, Kensuke Arakawa, Toshimitsu Hatabu

    Bioscience of microbiota, food and health   41 ( 1 )   12 - 19   2022.1

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    Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMFH Press  

    This study aimed to evaluate the benefits of oral administration of Lactobacillus acidophilus strain L-55 (LaL-55) to chickens inoculated with a Newcastle disease virus (NDV)-based live-attenuated vaccine by examining the mRNA expression of several genes related to viral infection in the spleen and ileum by quantitative reverse transcription polymerase chain reaction. In the spleen, interferon (IFN)-α was significantly higher in the low- and middle-dose LaL-55 groups at 6 weeks than at 4 weeks. IFN regulatory factor (IRF)-3 and IRF-7 expression was significantly higher in the low-dose LaL-55 group than in the middle- and high-dose LaL-55 groups. In the ileum, melanoma differentiation-associated gene 5 showed a dose-dependent increase at 4 weeks. IFN-γ and IRF-7 showed dose-dependent increases at 6 weeks. These results suggested that LaL-55 boosts the immune response to the NDV vaccine, albeit by different mechanisms in the spleen and ileum.

    DOI： 10.12938/bmfh.2021-026

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  • Reduction of macrophages by carrageenan decreases oocyst output and modifies local immune reaction in chick cecum with Eimeria tenella. International journal

    Dung Thi Ho, Hung Hoang Son Pham, Wataru Aota, Makoto Matsubayashi, Naotoshi Tsuji, Toshimitsu Hatabu

    Research in veterinary science   139   59 - 66   2021.10

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    DOI： 10.1016/j.rvsc.2021.07.003

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  • Relationship between Eimeria tenella associated-early clinical signs and molecular changes in the intestinal barrier function. International journal

    Hung Hoang Son Pham, Makoto Matsubayashi, Naotoshi Tsuji, Toshimitsu Hatabu

    Veterinary immunology and immunopathology   240   110321 - 110321   2021.10

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    DOI： 10.1016/j.vetimm.2021.110321

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  • Involvement of cancer-derived EMT cells in the accumulation of 18F-fluorodeoxyglucose in the hypoxic cancer microenvironment. International journal

    Sachi Sugita, Masanori Yamato, Toshimitsu Hatabu, Yosky Kataoka

    Scientific reports   11 ( 1 )   9668 - 9668   2021.5

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    DOI： 10.1038/s41598-021-88414-1

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  • Alteration of chemokine production in bovine endometrial epithelial and stromal cells under heat stress conditions. International journal

    Shunsuke Sakai, Toshimitsu Hatabu, Yuki Yamamoto, Koji Kimura

    Physiological reports   8 ( 22 )   e14640   2020.11

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    DOI： 10.14814/phy2.14640

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  • Morphological and molecular identification of Eimeria spp. in breeding chicken farms of Japan. Reviewed

    Makoto Matsubayashi, Tomoyuki Shibahara, Tomohide Matsuo, Toshimitsu Hatabu, Junya Yamagishi, Kazumi Sasai, Takashi Isobe

    The Journal of veterinary medical science   82 ( 5 )   516 - 519   2020.5

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    DOI： 10.1292/jvms.19-0661

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  • Apoptosis inhibition mitigates aging effects in Drosophila melanogaster. Reviewed International journal

    Hiroaki Kidera, Toshimitsu Hatabu, Kazuo H Takahashi

    Genetica   148 ( 2 )   69 - 76   2020.4

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    DOI： 10.1007/s10709-020-00088-1

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    Other Link： http://link.springer.com/article/10.1007/s10709-020-00088-1/fulltext.html

  • Daily Meal Supplemented with Astaxanthin-Enriched Yolk Has Mitigative Effects against Hypertension in Spontaneously Hypertensive Rats. Reviewed

    Toshimitsu Hatabu, Takumi Harada, Yuri Takao, Dung Ho Thi, Akihiro Yamasato, Tatsuya Horiuchi, Atsuya Mochizuki, Yasuhiro Kondo

    Biological & pharmaceutical bulletin   43 ( 3 )   404 - 408   2020.3

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    DOI： 10.1248/bpb.b19-01013

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  • Oral administration of the probiotic bacterium Lactobacillus acidophilus strain L-55 modulates the immunological parameters of the laying hen inoculated with a Newcastle disease virus-based live attenuated vaccine. Reviewed

    Dung Thi Ho, Toshimitsu Hatabu, Yosuke Sunada, Yasuhiro Kondo

    Bioscience of microbiota, food and health   39 ( 3 )   117 - 122   2020

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    DOI： 10.12938/bmfh.2019-033

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  • Transitions in morphological forms and rapid development of the asexual schizonts of Eimeria tenella through serial passaging in chicks. Reviewed International journal

    Makoto Matsubayashi, Hiroki Yamaguchi, Takeshi Hatta, Fumiya Kawahara, Toshimitsu Hatabu, Hiroshi Iseki, Junya Yamagishi, Takashi Isobe, Isao Teramoto, Akira Kaneko, Kiyoshi Kita, Naotoshi Tsuji, Kazumi Sasai

    Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases   75   103993 - 103993   2019.11

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    DOI： 10.1016/j.meegid.2019.103993

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  • Mulberry juice freeze-dried powder attenuates the disease severity by the maintaining of colon mucosa in mice with DSS-induced acute colitis. Reviewed International journal

    Yang Wang, Toshimitsu Hatabu

    Bioscience, biotechnology, and biochemistry   83 ( 5 )   914 - 922   2019.5

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    DOI： 10.1080/09168451.2019.1580135

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  • 鶏コクシジウム症 アイメリア・テネラ感染メカニズムの解明に向けて Invited

    畑生 俊光

    岡山実験動物研究会報   34 ( 34 )   17 - 20   2018.4

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  • Antiplasmodial properties of kaempferol-3-O-rhamnoside isolated from the leaves of Schima wallichii against chloroquine-resistant Plasmodium falciparum. Reviewed International journal

    Melisa I Barliana, Eka W Suradji, Rizky Abdulah, Ajeng Diantini, Toshimitsu Hatabu, Junko Nakajima-Shimada, Anas Subarnas, Hiroshi Koyama

    Biomedical reports   2 ( 4 )   579 - 583   2014.7

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    Previous intervention studies have shown that the most effective agents used in the treatment of malaria were isolated from natural sources. Plants consumed by non-human primates serve as potential drug sources for human disease management due to the similarities in anatomy, physiology and disease characteristics. The present study investigated the antiplasmodial properties of the primate-consumed plant, Schima wallichii (S. wallichii) Korth. (family Theaceae), which has already been reported to have several biological activities. The ethanol extract of S. wallichii was fractionated based on polarity using n-hexane, ethyl acetate and water. The antiplasmodial activity was tested in vitro against chloroquine-resistant Plasmodium falciparum (P. falciparum) at 100 μg/ml for 72 h. The major compound of the most active ethyl acetate fraction was subsequently isolated using column chromatography and identified by nuclear magnetic resonance. The characterized compound was also tested against chloroquine-resistant P. falciparum in culture to evaluate its antiplasmodial activity. The ethanol extract of S. wallichii at 100 μg/ml exhibited a significant parasite shrinkage after 24 h of treatment. The ethyl acetate fraction at 100 μg/ml was the most active fraction against chloroquine-resistant P. falciparum. Based on the structural characterization, the major compound isolated from the ethyl acetate fraction was kaempferol-3-O-rhamnoside, which showed promising antiplasmodial activity against chloroquine-resistant P. falciparum with an IC50 of 106 μM after 24 h of treatment. The present study has provided a basis for the further investigation of kaempferol-3-O-rhamnoside as an active compound for potential antimalarial therapeutics.

    DOI： 10.3892/br.2014.271

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  • Changes in estrogen receptor expression in the chick thymus during late embryonic development. Reviewed International journal

    Masafumi Katayama, Tomokazu Fukuda, Toshimitsu Hatabu, Kiyoaki Narabara, Asaki Abe, Yasuhiro Kondo

    Animal science journal = Nihon chikusan Gakkaiho   85 ( 3 )   277 - 85   2014.3

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    DOI： 10.1111/asj.12114

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  • Antiplasmodial prperties of kaempferol-3-O-rhamnoside isolated from leaves of Schima wallichii against chloroquine-resistant Plasmodium falciparum. Reviewed

    HATABU Toshimitsu

    2   579 - 583   2014

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  • Approach to epidemiological mechanism of infection or colonization of egg-laying chicken farms by Salmonella enterica Serovar enteritidis (SE) becoming the main source of contamination in food poisoning. Reviewed

    HATABU Toshimitsu

    5   376 - 392   2014

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  • Derivatives of Dictyostelium discoideum differentiation-inducing factor-3 suppress the activities of Trypanosoma cruzi in vitro and in vivo. Reviewed International journal

    Junko Nakajima-Shimada, Toshimitsu Hatabu, Yukari Hosoi, Yoko Onizuka, Haruhisa Kikuchi, Yoshiteru Oshima, Yuzuru Kubohara

    Biochemical pharmacology   85 ( 11 )   1603 - 10   2013.6

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    DOI： 10.1016/j.bcp.2013.03.007

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  • Selenium-induced apoptosis-like cell death in Plasmodium falciparum. Reviewed International journal

    Eka W Suradji, Toshimitsu Hatabu, Kenji Kobayashi, Chiho Yamazaki, Rizky Abdulah, Minato Nakazawa, Junko Nakajima-Shimada, Hiroshi Koyama

    Parasitology   138 ( 14 )   1852 - 62   2011.12

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    DOI： 10.1017/S0031182011001399

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  • The role of VAMP7/TI-VAMP in cell polarity and lysosomal exocytosis in vivo. Reviewed International journal

    Mahito Sato, Shinichiro Yoshimura, Rika Hirai, Ayako Goto, Masataka Kunii, Nur Atik, Takashi Sato, Ken Sato, Reiko Harada, Junko Shimada, Toshimitsu Hatabu, Hiroshi Yorifuji, Akihiro Harada

    Traffic (Copenhagen, Denmark)   12 ( 10 )   1383 - 93   2011.10

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    DOI： 10.1111/j.1600-0854.2011.01247.x

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  • Efficacy of mefloquine treatment and genetic profiles in uncomplicated Plasmodium falciparum malaria in southern Lao PDR. Reviewed International journal

    Hiromu Toma, Toshimitsu Hatabu, Viengxay Vanisaveth, M Kaiissar Mannoor, Hisami Watanabe, Changchun Li, Jun Kobayashi, Samlane Phompida, Shigeyuki Kano, Yoshiya Sato

    The Southeast Asian journal of tropical medicine and public health   42 ( 4 )   759 - 63   2011.7

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  • Trypanosoma cruzi infection induces nitric oxide production and S-nitrosylation of cellular FLIP in host cells

    J. Shimada, T. Hatabu

    XII INTERNATIONAL CONGRESS OF PARASITOLOGY (ICOPA)   117 - 120   2010

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  • Association of molecular markers in Plasmodium falciparum crt and mdr1 with in vitro chloroquine resistance: A Philippine study International journal

    Toshimitsu Hatabu, Moritoshi Iwagami, Shin-ichiro Kawazu, Nao Taguchi, Aleyla D. Escueta, Elena A. Villacorte, Pilarita T. Rivera, Shigeyuki Kano

    PARASITOLOGY INTERNATIONAL   58 ( 2 )   166 - 170   2009.6

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    DOI： 10.1016/j.parint.2009.01.010

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  • Genetic diversity and population structure of Plasmodium falciparum in the Philippines. International journal

    Moritoshi Iwagami, Pilarita T Rivera, Elena A Villacorte, Aleyla D Escueta, Toshimitsu Hatabu, Shin-ichiro Kawazu, Toshiyuki Hayakawa, Kazuyuki Tanabe, Shigeyuki Kano

    Malaria journal   8   96 - 96   2009.5

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    DOI： 10.1186/1475-2875-8-96

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  • マラリア原虫Plasmodium falciparumに対する無機セレン化合物の抗マラリア活性についての検討(Inorganic selenium parasiticidal effect on human malaria parasite Plasmodium falciparum in vitro) Reviewed

    スラジ・エカ, 畑生 俊光, 小林 健司, アブドゥラ・リズキー, 中澤 港, 嶋田 淳子, 小山 洋

    Biomedical Research on Trace Elements   19 ( 2 )   214 - 214   2008.6

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  • Phylogenetic relationship of Plasmodium falciparum populations in the Philippines. Reviewed International journal

    Moritoshi Iwagami, Toshimitsu Hatabu, Shin-Ichiro Kawazu, Aleyla S Escueta, Elena A Villacorte, Pilarita Tongol-Rivera, Shigeyuki Kano

    The Southeast Asian journal of tropical medicine and public health   39 ( 2 )   200 - 4   2008.3

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  • Plasmodium falciparum: the fungal metabolite gliotoxin inhibits proteasome proteolytic activity and exerts a plasmodicidal effect on P. falciparum. International journal

    Toshimitsu Hatabu, Masaki Hagiwara, Nao Taguchi, Masayuki Kiyozawa, Mamoru Suzuki, Shigeyuki Kano, Kumiko Sato

    Experimental parasitology   112 ( 3 )   179 - 83   2006.3

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    The in vitro antimalarial activity of the fungal metabolite gliotoxin (GTX) was evaluated, and its mechanism of action was studied. GTX showed plasmodicidal activity against both Plasmodium falciparum chloroquine-resistant strain K-1 and chloroquine-susceptible strain FCR-3. GTX cytotoxicity was significantly lower against a normal liver cell line (Chang Liver cells). The intracellular reduced glutathione level of parasitized and of normal red blood cells was not affected by GTX treatment. However, GTX decreased the chymotrypsin-like activity of parasite proteasomes in a time-dependent manner. The results of this study indicate that GTX possesses plasmodicidal activity and that this effect is due to inhibition of parasite proteasome activity, suggesting that GTX may constitute a useful antimalarial therapy.

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  • Pyrimethamine-sulfadoxine treatment of uncomplicated Plasmodium falciparum malaria in Lao PDR. International journal

    M Kaiissar Mannoor, Viengxay Vanisaveth, Boualy Keokhamphavanh, Hiromu Toma, Hisami Watanabe, Jun Kobayashi, Toshimitsu Hatabu, Nao Taguchi, Bousy Hongvangthong, Rattanaxay Phetsouvanh, Samlane Phompida, Shigeyuki Kano, Yoshiya Sato

    The Southeast Asian journal of tropical medicine and public health   36 ( 5 )   1092 - 5   2005.9

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    A 28-day in vivo treatment trial to evaluate the efficacy of pyrimethamine/sulfadoxine (Fansidar, PS) was conducted in 21 Lao patients with uncomplicated Plasmodium falciparum malaria. Sixteen patients (76%) were completely cured with PS without any reappearance of asexual stage parasitemia during the follow-up examination. On the other hand, 5 patients (24%) failed to respond to this trial medication, resulting in recrudescence of asexual stage P. falciparum malaria. PS resistance resulted in higher prevalence of post-treatment gametocytemia, 25% gametocyte carriers among PS sensitive cases versus 75% of the resistant cases. These findings suggest that although the level of PS resistance is still valid for treatment of malaria in the study area of Lao PDR, post-treatment induction of gametocytemia among resistant cases may result an increase in transmission rate of PS resistant falciparum malaria.

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

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

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

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    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.

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  • A pilot field survey on the in vitro drug susceptibility of Plasmudium falciparum in Lao PDR. Tropical Medicine and Health. Reviewed

    Hatabu T, Vanisaveth V, Taguchi N, Kobayashi J, Mannor KM, Watanabe H, Toma H, Phompida S, Kano S

    Trop. Med. Health   33   103 - 104   2005

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

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    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.

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

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    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.

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

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    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.

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

    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

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    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.

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  • [Severe falciparum malaria with prolonged hemolytic anemia after successful treatment with intravenous artesunate].

    Ichiro Itoda, Takeshi Yasunami, Ken Kikuchi, Hisashi Yamaura, Kyoichi Totsuka, Kentaro Yoshinaga, Masanao Teramura, Hideaki Mizoguchi, Toshimitsu Hatabu, Shigeyuki Kano

    Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases   76 ( 8 )   600 - 3   2002.8

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    We report a 68-year-old woman with severe falciparum malaria contracted in Tanzania. She presented high parasitemia and was treated successfully with intravenous artesunate, a qinghaosu derivative, and aggressive supportive therapy. She developed hemolytic anemia and jaundice on day 11 and blood transfusion was required. This case illustrates that intravenous artesunate has excellent antimalarial activity with rapid efficacy and that no severe adverse effect but conventional aggressive supportive therapy is still important in the treatment of severe falciparum malaria.

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  • The expression system of biologically active canine interleukin-8 in Leishmania promastigotes. International journal

    Toshimitsu Hatabu, Yasunobu Matsumoto, Shin-ichiro Kawazu, Yuko Nakamura, Tsugihiko Kamio, Hong Gang Lu, Kwang-Poo Chang, Yoshihisa Hashiguchi, Shigeyuki Kano, Takashi Onodera, Yoshitsugu Matsumoto

    Parasitology international   51 ( 1 )   63 - 71   2002.3

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    It has been reported that Leishmania promastigotes have ability to express foreign genes on drug selectable plasmids. To investigate further abilities of the recently described expression vector, P6.5, in the transfection of Leishmania organisms (Chen D-Q, Kolli BK, Yadava N et al. Episomal expression of specific sense and antisense mRNAs in Leishmania amazonensis: modulation of gp63 levels in promastigotes and their infection of macrophages in vitro. Infect Immun 2000;68:80--86), the constructed expression vector, which contains canine interleukin-8 (cIL-8) coding cDNA, was introduced by electroporation to promastigotes of four species of the genus Leishmania: Leishmania amazonensis, L. equatorensis, L. donovani and L. infantum. Extrachromosomal DNAs and total RNAs from the transfected promastigotes were subjected to polymerase chain reaction (PCR) and reverse transcriptase-PCR, respectively, using cIL-8 gene specific primers, and a predicted product of 330 bp was detected. Western blot analysis using a mouse monoclonal antibody raised against cIL-8 demonstrated the successful expression of cIL-8 in the transfectants and culture supernatants. Culture supernatants of the transfected L. amazonensis and L. equatorensis promastigotes showed a high chemotactic activity to both dog and mouse polymorphonuclear leukocytes. These results indicate that Leishmania promastigotes transfected with the expression vector P6.5 containing cIL-8 cDNA are capable of producing biologically active cIL-8. The Leishmania expression system using the P6.5 vector might be a useful alternative for the production of biologically active recombinant cytokines.

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  • PCR-amplification, sequencing, and comparison of the var/PfEMP-1 gene from the blood of patients with falciparum malaria in the Philippines. International journal

    Nozomu Ikenoue, Shin-ichiro Kawazu, Toshimitsu Hatabu, Elena A Villacorte, Pilarita T Rivera, Shigeyuki Kano

    The Southeast Asian journal of tropical medicine and public health   33 Suppl 3   8 - 13   2002

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    The adhesion of Plasmodium falciparum-infected erythrocytes to vascular endothelium and to uninfected red blood cells (RBCs) plays a key role in the pathology of severe malaria. Adhesion is known to be mediated in part by the antigenically-variant erythrocyte membrane protein-1 (PfEMP-1), which is encoded by the var-gene family of P. falciparum. It has recently been reported that in vitro a single parasite simultaneously transcribes multiple var-genes but that, through a developmentally regulated process, the parasite selects only one PfEMP-1 that will to reach the surface of the host RBC. Were this to be true in vivo, one would expect a correlation between the type of var/PfEMP-1 that is expressed on the parasite-infected RBC and the severity of clinical disease. In order to test this assumption, we determined the sequence of the var-gene that was expressed by the parasites in patients' blood samples. Seven blood samples were collected from patients with or without severe clinical symptoms (cerebral malaria): two samples were from patients diagnosed as having imported falciparum malaria at the International Medical Center of Japan (IMCJ); the five others were from patients of the Davao Regional Hospital in Davao, the Philippines. The parasites (ring stage) in the blood samples were cultured for 24 hours; the matured trophozoites, in which the var-gene selection had taken place, served as material for mRNA isolation. The cDNA corresponding to the Duffy-binding-like (DBL)-1 domain of the var-gene was amplified by RT-PCR, using a region-specific primer set. The amplified cDNAs were cloned into the plasmid vector; the resultant clones (32) were sequenced on both strands. The results indicated that there was considerable diversity in the sequence of the DBL-1 domain among the clones, even among those from a single patient. In conclusion, it was difficult to demonstrate the correlation between the type of var-gene transcripts found in the RBCs of malaria patients and the severity of their symptoms.

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Presentations

  • Scavenger receptor-Aは分子内cysteine-rich領域で熱帯熱マラリア原虫感染赤血球と接着する

    感染症沖縄フォーラム  2010 

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  • 熱帯熱マラリア原虫感染赤血球に対する新規接着因子としてのスカベンジャー受容体MARCOの同定

    日本寄生虫学会  2010 

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  • スカベンジャーレセプターMARCOは分子内領域SRCR domainを用いて熱帯熱マラリア感染赤血球と接着する

    感染症沖縄フォーラム  2010 

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  • CXCL16/SR-PSOX, membrane-bound form chemokine/a member of scavenger receptor, acts as a receptor of both the cytoadherence and erythrophagocytosis in severe malaria.

    2009 

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  • Class A scavenger receptor mediates the cytoadherence of Plasmodium falciparum-infected erythrocytes.

    The 9th Awaji International Forum on Infection and Immunity  2009 

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  • Class A scavenger receptor mediates the cytoadherence of Plasmodium falciparum-infected erythrocytes.

    The 9th Awaji International Forum on Infection and Immunity  2009 

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  • CXCL16/SR-PSOX, membrane-bound form chemokine/a member of scavenger receptor, acts as a receptor of both the cytoadherence and erythrophagocytosis in severe malaria.

    2009 

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  • 新規細胞接着因子としてのScavenger Receptor with C type Lectin (SRCL) の同定

    日本寄生虫学会  2009 

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  • Scavenger receptor-Aは分子内cystein-rich領域で熱帯熱マラリア原虫感染赤血球を認識する。

    分子寄生虫マラリアフォーラム  2009 

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  • 重症マラリア病態形成に関るスカベンジャーレセプターの役割

    第6回感染症沖縄フォーラム  2008 

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  • SR-PSOX/CXCL16, scavenger receptor/membrane bound form chemokine, is a cytoadherence-related molecule to Plasmodium falciparum-infected erythrocytes

    XVIIth International Congress of Tropical Medicine and Malaria  2008 

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  • 新規細胞接着因子としてのスカベンジャーレセプターＡの解析

    2008 

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  • SR-PSOX/CXCL16, scavenger receptor/membrane bound form chemokine, is a cytoadherence-related molecule to Plasmodium falciparum-infected erythrocytes

    XVIIth International Congress of Tropical Medicine and Malaria  2008 

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  • Scavenger receptor/membrane-bound form chemokine, SR-PSOX/CXCL16, mediates the phagocytosis of Plasmodium falciparum-infected erythrocytes by mononuclear phagocytes and the cytoadherence to the endothelial cells.

    The 1st International Conference on Malaria Vaccines for the World  2007 

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    Presentation type：Poster presentation  

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  • 重症マラリア病態形成因子としてのスカベンジャーレセプターの解析

    分子寄生虫学ワークショップ  2007 

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  • 熱帯熱マラリア原虫に対するアムホテリシンＢの発育阻止機序の解析

    第76回日本寄生虫学会  2007 

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  • 貪食細胞はマラリア原虫感染によりどのように変化するか？

    第15回分子寄生虫学ワークショップ  2007 

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  • Scavenger receptor/membrane-bound form chemokine, SR-PSOX/CXCL16, mediates the phagocytosis of Plasmodium falciparum-infected erythrocytes by mononuclear phagocytes and the cytoadherence to the endothelial cells.

    The 1st International Conference on Malaria Vaccines for the World  2007 

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  • マラリア原虫感染赤血球に対する接着・貪食因子としての膜結合型ケモカインCXCL16の同定

    第五回分子寄生虫マラリア研究フォーラム  2006 

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  • 熱帯熱マラリア原虫感染赤血球に対する新規細胞接着因子としての膜結合型ケモカインCXCL16の同定

    第75回日本寄生虫学会  2006 

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  • Trypanosoma cruzi infection inhibits Fas-mediated host-cell apoptosis and induces c-FLIP expression.

    The 20th IUBMB Congress and 11th FAOBMB Congress  2006 

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  • Molecular Epidemiology of Plasmodium falciparum in the Philippines

    Joint International Tropical Medicine Meeting 2006 and 6th Asia-Pacific Travel Health Conference  2006 

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  • 真菌由来化合物ヒポクレリンAの抗マラリア効果の検討

    第75回日本寄生虫学会  2006 

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  • Trypanosoma cruzi感染細胞におけるc-FLIPのユビキチン化機構の解析

    第75回日本寄生虫学会  2006 

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  • 真菌由来化合物ヒポクレリンAの抗マラリア効果の検討

    日本寄生虫学会  2006 

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  • Trypanosoma cruzi infection inhibits Fas-mediated host-cell apoptosis and induces c-FLIP expression.

    The 20th IUBMB Congress and 11th FAOBMB Congress  2006 

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  • 熱帯熱マラリア原虫感染赤血球に対する新規細胞接着因子としての膜結合型ケモカインCXCL16の同定

    日本寄生虫学会  2006 

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  • Molecular Epidemiology of Plasmodium falciparum in the Philippines

    Joint International Tropical Medicine Meeting 2006 and 6th Asia-Pacific Travel Health Conference  2006 

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  • Inhibition of Fas-mediated host-cell apoptosis by Trypanosoma cruzi infection:Up-regulation of anti-apoptotic host proteins.

    The 5th Awaji International Forum on Infection and Immunity  2005 

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  • 群馬県内成人のトキソプラズマ抗体保有状況 －ここ10年間でどう変化したか-

    第74回日本寄生虫学会  2005 

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  • フィリピンで分離した熱帯熱マラリア原虫株のクロロキン耐性関連遺伝子pfcrt変異とin vitro CQ感受性の相関について

    第65回日本寄生虫学会東日本支部会  2005 

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  • Malaria vaccine candidate using enolase antigen of Plasmodium falciparum. Medicine and Health in the Topics

    XVth Internatiopnal Congress for Tropical Medicine and Malaria  2005 

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  • 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

    北関東医学会  2005 

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  • 群馬県におけるToxoplasma gondii抗体保有率の推移

    北関東医学会  2005 

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  • 熱処理アムホテリシンＢによる抗マラリア効果の検討

    第74回日本寄生虫学会  2005 

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  • Inhibition of Fas-mediated host-cell apoptosis by Trypanosoma cruzi infection:Up-regulation of anti-apoptotic host proteins.

    The 5th Awaji International Forum on Infection and Immunity  2005 

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  • Malaria vaccine candidate using enolase antigen of Plasmodium falciparum. Medicine and Health in the Topics

    XVth Internatiopnal Congress for Tropical Medicine and Malaria  2005 

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  • 真菌由来抗生物質グリオトキシンによる抗マラリア原虫効果の検討

    第74回日本寄生虫学会  2005 

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  • アムホテリシンＢの抗マラリア効果の検討

    第73回日本寄生虫学会  2004 

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  • in vitro drug susceptibility and genetic variation of Plasmodium falciparum isolates from Thai-Myanmer border

    Joint International Tropical Medicine Meeting 2004  2004 

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  • Plasmodium falciparum-infected erythrocytes bind to the membrane-bound form of Fractalkine/CX3CL1

    日独原虫病学会  2004 

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  • Plasmodium falciparum-infected erythrocytes bind to the membrane-bound form of Fractalkine/CX3CL1

    日独原虫病学会  2004 

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  • 生薬由来成分による抗マラリア効果の検討

    第７３回日本寄生虫学会大会  2004 

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  • 生薬由来成分による抗マラリア効果の検討

    第７３回日本寄生虫学会大会  2004 

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  • in vitro drug susceptibility and genetic variation of Plasmodium falciparum isolates from Thai-Myanmer border

    Joint International Tropical Medicine Meeting 2004  2004 

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  • 新規マラリア原虫感染赤血球接着分子としての膜結合型フラクタルカインの同定

    第73回日本寄生虫学会  2003 

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  • 群馬県における幼児および児童・生徒の蟯虫卵保有状況の年次推移

    第73回日本寄生虫学会  2003 

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  • 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

    第72回日本寄生虫学会  2003 

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  • ネズミマラリア原虫ペルオキシレドキシンの蚊体内発育ステージにおける発現

    第71回日本寄生虫学会  2002 

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  • フィリピンミンダナオ島における熱帯熱マラリア原虫クロロキン感受性の検討

    第71回日本寄生虫学会  2002 

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  • ネズミマラリア原虫Plasmodium berghei強毒株、弱毒株間におけるプロテオーム解析の試み

    第71回日本寄生虫学会  2002 

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  • ネズミマラリア原虫ペルオキシレドキシンの蚊体内発育ステージにおける発現

    第133回日本獣医学会  2002 

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  • マラリア原虫感染赤血球を貪食したマクロファージの応答性についての解析

    第71回日本寄生虫学会  2002 

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  • 熱帯熱マラリア原虫2-Cys型ペルオキシレドキシンの性状解析

    第70回日本寄生虫学会  2001 

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  • Antibody reaction to the Plasmodium falciparum enolase, a glycolytic enzyme

    The 50th annual meeting of the American Society of Tropical Medicine and Hygine  2001 

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  • 熱帯熱マラリア原虫における抗酸化酵素ペルオキシレドキシンの過剰発現株の作製

    第70回日本寄生虫学会  2001 

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  • Role of ploymorphonuclear leukocytes in cutaneous leishmaniasis

    WORLDleish2  2001 

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  • Antibody reaction to the Plasmodium falciparum enolase, a glycolytic enzyme

    The 50th annual meeting of the American Society of Tropical Medicine and Hygine  2001 

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  • Differentiation of leishmaniasis species complexes based on PCR amplificasion of highly conserved gene(gp36)

    WORLDleish2  2001 

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  • PCR-based differentiation of the species complexes in Leishmania spp.

    WORLDleish2  2001 

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  • CD4+ cells are indespensable for ulcer development in murine cutaneous leishmaniasis

    WORLDleish2  2001 

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  • Differentiation of leishmaniasis species complexes based on PCR amplificasion of highly conserved gene(gp36)

    WORLDleish2  2001 

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  • フィリピンミンダナオ島における熱帯熱マラリア原虫の薬剤感受性ー酸素吸収炭酸ガス発生剤を用いた薬剤感受性試験ー

    第42回日本熱帯医学会  2001 

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  • P. berghei XAT感染Beigeマウスにおける肝臓および脾臓浸潤細胞の免疫組織学的検討

    第70回日本寄生虫学会  2001 

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  • Role of ploymorphonuclear leukocytes in cutaneous leishmaniasis

    WORLDleish2  2001 

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  • CD4+ cells are indespensable for ulcer development in murine cutaneous leishmaniasis

    WORLDleish2  2001 

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  • 熱帯熱マラリア原虫由来解糖系酵素エノラーゼをターゲットとした原虫増殖抑止能に関する基礎的研究

    第70回日本寄生虫学会  2001 

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  • 熱帯熱マラリア原虫におけるビタミンA代謝機構の解明

    第70回日本寄生虫学会  2001 

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  • 2-Cys型ペルオキシレドキシンの性状解析

    第131回日本獣医学会  2001 

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  • 野外調査地における簡易検査キットOptiMALによるマラリア診断の有効性の検討

    第12回日本臨床寄生虫学会  2001 

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  • PCR-based differentiation of the species complexes in Leishmania spp.

    WORLDleish2  2001 

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Industrial property rights

  • 脂肪蓄積抑制剤及びその製造方法並びに血糖値上昇抑制剤及び腸内細菌叢改善剤

    神崎 浩, 仁戸田 照彦, 畑生 俊光

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    Applicant：国立大学法人 岡山大学

    Application no：特願2020-004396  Date applied：2020.1.15

    Announcement no：特開2021-109865  Date announced：2021.8.2

    J-GLOBAL

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  • 抗マラリア薬有効成分としてのグリオトキシンの新規用途、及びグリオトキシンを有効成分とする抗マラリア薬。

    佐藤 久美子, 畑生 俊光, 萩原 昌樹, 清澤 正幸, 鈴木 守

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    Applicant：国立大学法人群馬大学

    Application no：特願2005-069560  Date applied：2005.3.11

    Announcement no：特開2006-249019  Date announced：2006.9.21

    J-GLOBAL

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  • 植物精油成分を含む殺菌剤と該殺菌剤を用いた感染症予防方法

    佐藤 久美子, 田村 遵一, 畑生 俊光, 小池 弘人, 佐藤 浩子

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    Applicant：佐藤 久美子

    Application no：特願2004-300925  Date applied：2004.10.15

    Announcement no：特開2006-111577  Date announced：2006.4.27

    J-GLOBAL

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  • 微細霧を用いた消臭、病原微生物処理及び香気散布に係る方法

    佐藤 久美子, 田村 遵一, 畑生 俊光, 小池 弘人

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    Applicant：佐藤 久美子

    Application no：特願2003-281534  Date applied：2003.7.29

    Announcement no：特開2005-046338  Date announced：2005.2.24

    J-GLOBAL

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Awards

  • トピックス賞

    2025.4   日本農芸化学会  

    安藤亜麻菜, 松林誠, 畑生俊光

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  • 第14回奨励賞

    2005  

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    Country：Japan

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  • パイオニア・スピリット賞

    2001  

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    Country：Japan

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Research Projects

  • Bioarchaeology of Human Migration in the Formation and Development of the Ancient Maya

    Grant number：24H00102  2024.04 - 2028.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    鈴木 真太郎, 山下 勝行, 畑生 俊光, 飯塚 義之

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    Grant amount：\46540000 （ Direct expense: \35800000 、 Indirect expense：\10740000 ）

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  • 消化管共生ネットワークを基盤とする草食性希少野生鳥類の新規保全モダリティの構築

    Grant number：23K26932  2023.04 - 2026.03

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    松林 誠, 牛田 一成, 土田 さやか, 倉持 幸司, 畑生 俊光, 芝原 友幸, 笹井 和美

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    Grant amount：\17030000 （ Direct expense: \13100000 、 Indirect expense：\3930000 ）

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  • 5-ALA産生乳酸菌の作製とその家畜用ワクチンプラットホームとしての可能性

    Grant number：23K23763  2022.04 - 2026.03

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    畑生 俊光, 荒川 健佑

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    Grant amount：\17550000 （ Direct expense: \13500000 、 Indirect expense：\4050000 ）

    本研究年度は、①有用乳酸菌株の選択および②5-ALA産生乳酸菌の作製を目標に研究を行った。このうち、①について約20日齢の白色レグホーン種幼雛および約500日齢のロードアイランドレッド種成鶏雌腸管より乳酸菌の分離を試みた。腸管内容物は滅菌生理食塩水で段階希釈後、シクロヘキシミドを添加した各種寒天培地にて塗抹培養した。培養は嫌気的に40℃で48時間行った。幼雛腸管内の生菌数は6.23-9.36 log CFU/gで、大腸を除いて下部にいくほど菌数が多かった（十二指腸＜空腸＜大腸＜回腸＜盲腸だった）。一方、成鶏腸管の生菌数は部位ごとの差は幼雛ほど大きくなく、8.23-9.24 log CFU/gであった。分離培地ごとの生菌数の差はそれほど見られず、明確な傾向はなかった。次に、なるべく形態の異なるコロニーを釣菌・継代培養したところ、実験①からは培養可能な幼雛および成鶏腸管由来の233および418菌株がそれぞれ得られた。そして、培養液pH < 5.0となった230および389菌株を乳酸菌の候補として選抜した。②については、プラスミド選択および遺伝子導入用乳酸菌の検討にとどまった。
    一方、免疫賦活効果の高いアシドフィルス乳酸菌と5-ALAの同時給与による抗コクシジウム効果の検討を行った。その結果、アシドフィルス乳酸菌単独投与時で対照群と比較して約60％のオーシスト排出抑制効果がみられたが、5-ALAをアシドフィルス菌と同時給与することにより約80％のオーシスト排出抑制効果が認められた。

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  • Studies on host autophagy and apoptosis in Trypanosoma cruzi infected cells

    Grant number：24590502  2012.04 - 2016.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Shimada Junko, HATABU Toshimitsu

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    Grant amount：\5460000 （ Direct expense: \4200000 、 Indirect expense：\1260000 ）

    Autophagy has emerged as an essential component of the defense system against intracellular pathogens. We demonstrated that Trypanosoma cruzi, an intracellular protozoan parasite, was not eliminated by host autophagic machinery. Puncta of LC3, an autophagy marker, were significantly increased after the infection, indicating that T. cruzi infection activated the early step of host autophagy. However, the degradation of p62, with a known marker in autolysosome formation, and autolysosomes were not observed in the infected cells. These results indicated that T. cruzi infection inhibits host autophagy pathway before the autolysosome formation. Furthermore, autophagosome formation was inhibited at the step of conversion from LC3-Atg3 to LC3-Ⅱin T. cruzi infected cells.

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  • Analysis of the factors of host-parasite relationship in severe malaria pathology

    Grant number：23790457  2011 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

    HATABU Toshimitsu, SHIMADA Junko, AMEMIYA Kenji, MIYAMOTO Yuto, MIYASHITA Daichi

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    Grant amount：\4420000 （ Direct expense: \3400000 、 Indirect expense：\1020000 ）

    1) To confirm the ligands to SRs, the candidate proteins were searched on the PlasmoDB. Four of the Plasmodiumproteins were identified and their recombinant proteins were successfully made by common methods using E. coli, and now confirming their biological functions. 2) The expression of SRs was observed in mice infected with P. b e r g h e i ANKA (PbANKA). The expression of class A SR, MARCO, was markedly enhanced by PbANKA infection in lung, liver, and spleen, but not class B SR, CD36. MARCO was histopathologically expressed on the macrophages in marginal zone macrophages and endothelial cells in liver sinusoid. The differentiation of gene expression in both lethal and recovered mice group from P. y o e l l i17XL (Py17XL) infection were measuredby DNA microarray. The expression of 5893 in 59304 genes was enhanced in recovered group compared with lethal it. The results suggested that different types of macrophages were induced in both lethal (M2a macrophage) and recovered mice (M2c-like macrophage).

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  • Regulation of oxidative stress and apoptosis in Trypanosoma cruzi infected cells

    Grant number：21590461  2009 - 2011

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    SHIMADA Junko, HATABU Toshimitsu

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    Grant amount：\4680000 （ Direct expense: \3600000 、 Indirect expense：\1080000 ）

    In Trypanosoma cuzi infected cells, the production of reactive oxygen species including nitric oxide (NO) was increased and inducible nitric oxide synthase (iNOS) gene was up-regulated. The inhibition of apoptosis in infected cells was reduced by the addition of NOS inhibitors. Furthermore, cellular FLICE-like inhibitory protein (c-FLIP), an apoptosis inhibitory protein, was nitrosylated in T. cruzi infected cells.

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  • マラリア原虫による宿主免疫修飾機構の解析

    Grant number：21022009  2009 - 2010

    日本学術振興会  科学研究費助成事業  特定領域研究

    畑生 俊光

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    Grant amount：\7600000 （ Direct expense: \7600000 ）

    重症熱帯熱マラリアの病態形成機構は、マラリア原虫感染赤血球(pRBC)の宿主細胞への細胞接着が重要な現象と考えられ、未知因子の存在が推測されている。我々は、生体における老化赤血球などの排除機構に着目し、その排除に関わるスカベンジャーレセプター(SR)に着目した。SRsの重症マラリア病態形成機構への関与を検討する目的で、SRs強制発現細胞株を作製しpRBCとの接着を観察した。また、Plasmodium berghei ANKA(PbANKA)感染マウスモデルを用い、PbANKA感染前後の脳、肺、肝臓、脾臓、心臓における9種類のSRs(SR-A、NARCO、SRCL、CD36、CD68、SREC-I、SR-PSOX、FEEL-I、CD163)のmRNA発現について検討した。pRBCとSRsの接着を検討するために、SR-A、MARCO、SR-PSOX、CD68、SRCL、SREC-Iそれぞれについて強制発現細胞株を作製した。細胞接着試験の結果、SR-A、MARCO、SR-PSOX、SRCLおよびSREC-IについてはpRBCとの接着が観察されたが、CD68は観察されなかった。PbANKA感染マウスモデルの観察結果から、CD36、CD163、SR-PSOX、SREC-1、について感染前後の発現臓器毎の違いは認められなかったが、MARCOは、感染7日後に肝臓、脾臓、肺でmRNA発現増強が観察された。SR-Aは、感染前の肝臓で強く発現が観察されたが、感染7日後には全臓器で発現が増強した。FEEL-Iは感染前の発現は認められなかったが、感染3日後より全臓器での発現が観察された。本研究の結果から、貪食細胞表面に発現が報告されているSR-AおよびMARCOは、これらの臓器においてマラリア原虫感染により発現誘導されるpRBCの接着・貪食因子である可能性が推測された。一方、CD36やSR-PSOXは、血管内皮細胞やマクロファージに発現することが報告されているが、pRBC感染前後で発現臓器等に差が認められなかったことから、血管内皮細胞ではpRBC接着因子として、貪食細胞ではpRBC貪食因子として機能し、発現部位で機能が異なる可能性が推測された。

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  • Research of host molecules associated with the pathogenesis of severe malarial anemia

    Grant number：20790322  2008 - 2009

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

    HATABU Toshimitsu

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    Grant amount：\4420000 （ Direct expense: \3400000 、 Indirect expense：\1020000 ）

    Severe falciparum malaria such as cerebral malaria and severe anemia is leading cause of morbidity and mortality. Plasmodium falciparum-infected red blood cells (pRBCs) adhere to the endothelial cells via receptors expressed on the surface of the endothelial cells, sequester in the microvasculature of several organs. Severe anemia which may be due to a number of factors including rupture of the pRBCs and phagocytosis of pRBCs is another cause of death. However, the molecular mechanism underlying both the cytoadherence and erythrophagocytosis related with severe malaria is not completely understood. Here, we report that the pRBCs bind to the class A scavenger receptors, SR-A and MARCO, which is expressed on the surface of the activated phagocytes.
    To identify the cytoadherence of pRBCs to SR-A and MARCO, human SR-A or MARCO cDNA was transfected to CHO cells (CHO-SR-A or CHO-MARCO cells). Furthermore, several mutants of both molecules were made to identify the sites related with pRBC adherence. pRBCs adhered to the both CHO- SR-A and CHO-MARCO cells, but not to the CHO-mock cells. The pRBC did not observed adherence to the deletion mutants of SRCR domain in both scavenger receptors.
    These results may suggest that both SR-A and MARCO acts as a host factor related with cytoadherence of the pRBCs, and contribute to our present understanding the pathology of severe falciparum malaria.

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  • Genetic epidemiological research on drug resistant malaria which has originated and been spreading in Asian countries.

    Grant number：19406013  2007 - 2009

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    KANO Shigeyuki, MITAMURA Toshihide, HATABU Toshimitsu, IWAGAMI Moritoshi, TANABE Kazuyuki, KAWAZU Shin-Ichiro, NAKAZAWA Shusuke, TONGOL-RIVERA Pilarita, LOOAREESUWAN Sornchai, KRUDSOOD Srivicha, KHO Weon-Gyu, SOCHEAT Duong

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    Grant amount：\17030000 （ Direct expense: \13100000 、 Indirect expense：\3930000 ）

    In the malaria endemic Philippines, the level of genetic diversity of Plasmodium falciparum correlates with the local malaria endemicity. The Thai P.f.populations had been under strong chloroquine selective pressure but the Vietnamese population had not, and that the origin of chloroquine resistance in Vietnam might be different from Thailand. The genealogical origin of P. vivax populations in South Korea was from the two different populations in southern China. These findings confirm that population genetic analyses are a useful tool for epidemiology of malaria.

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  • Molecular mechanisms of Trypanosoma cruzi survival using host apoptosis inhibitor

    Grant number：18590398  2006 - 2007

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    SHIMADA Junko, HATABU Toshimitsu

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    Grant amount：\3990000 （ Direct expense: \3600000 、 Indirect expense：\390000 ）

    Trypanosoma cruzi is a protozoan parasite that causes Chagas' disease in South America. We demonstrated that the parasite infection inhibits death receptor-mediated apoptosis in host cells. This inhibition is thought to be a defense strategy for the parasite to escape from host immune responses. We clarified that the parasite dramatically up-regulates cellular FLICE-like inhibitory protein (c-FLIP), the only known mammalian inhibitor specific for death receptor signaling. We also found that c-FLIP knock-down with a small interfering RNA significantly restores Fas-mediated apoptosis in infected cells. To elucidate the mechanisms of c-FLIP up-regulation, we examined posttranscriptional regulation of c-FLIP expression in T. cruzi infected cells. It has been reported that c-FLIP is a key target for S-nitrosylation by nitric oxide (NO) in cancer cells. HT1080 or THP-1 cells were infected with T. cruzi or treated with NO donors, and further cultured for 1-3 days. Cell lysates were immunoprecipitated and analyzed by Western blot using anti-S-nitrosocysteine antibody in control and infected cells. By the addition of the NO donors, sodium nitroprusside, the nitrosylated level of FLIP was strongly increased. In infected cells nitrosylated c-FLIP was clearly detected in supernatant. These findings suggest that endogenously produced NO synthesized by NO synthase is a mediator of T. cruzi infection. S-nitrosylation of FLIP is an important mechanism utilized by NO rendering FLIP resistant to ubiquitination and proteasomal degradation by FasL.

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  • マラリア重症化における膜結合型ケモカインの機能的役割に関する研究

    Grant number：18790290  2006 - 2007

    日本学術振興会  科学研究費助成事業  若手研究(B)

    畑生 俊光

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    Grant amount：\3400000 （ Direct expense: \3400000 ）

    (1)研究計画より、次年度以降に検討するスカベンジャーレセプター(SR)をピックアップした。具体的には9 classに分類されるSRのうちclass Aに類されるもの3種類およびclass Fに類されるもの1種類をターゲットとする。これら4種類のうち研究計画を前倒ししてSR-AIについて発現細胞を作成し、マラリア原虫感染赤血球との接着を検討した。その結果、SR-AI発現細胞に対してマラリア原虫感染赤血球の接着が確認され、この接着は抗SR-AI抗体によって阻害されることが判明した。一方でアネキシンVでは阻害されなかった。その他については、現在蛋白発現細胞を作成している。
    (2)ヤウスモデルを使用した感染実験を計画していた。遺伝子一過性発現マウスの作成は行わなかった。一方、感染モデルでは感染経過と赤血球表面への感染経過に伴うホスファチジルセリン発現動態の検討を行った。その結果、原虫寄生率の上昇に平行してホスファチジルセリン陽性赤血球率も上昇した。しかしながら、ホスファチジルセリン陽性赤血球率は最高値約20%(寄生率最高値約40%)であった。その後寄生率の減少及び感染の終息に伴いホスファチジルセリン陽性赤血球率も漸減した。すなわち感染の推移とホスファチジルセリン陽性赤血球率の動態はほぼ一致した。
    SR-PSOXについては遺伝子破壊マウスの国内作成が確認されたことから、当該マウスの導入と感染実験を今後予定している。

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  • A genomic epidemiological research on a drug resistant malaria spreading in Asian countries.

    Grant number：16406012  2004 - 2006

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    KANO Shigeyuki, KAWAZU Shin-ichiro, HATABU Toshimitsu

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    Grant amount：\13300000 （ Direct expense: \13300000 ）

    A mutation from Lys to Thr in the codon 76 of Plasmodium falciparum chloroquine resistant transporter protein (PfCRT) is associated with CQ resistance, and the genotype is used as a molecular marker to monitor the distribution and frequency of the CQ resistant malaria. In the present study, selection of the resistant strain in mixed cultures of a drug resistant strain (K1 which shows K76T) and a susceptible strain (FCR-3 which shows 76K) under a low chloroquine pressure (<80nM) was nicely observed in vivo using real-time PCR analysis.
    Then, we analyzed the frequency of the mutation in codon 72-76 of the pfcrt gene and 3 microsatellite (MS) DNA markers flanking the pfcrt, using P. falciparum isolates from the Philippines, Thailand, and southern part of Vietnam. Thirty-nine isolates from Thailand showed identical K76T but 6 out of 13 isolates from the Philippines showed mixed type. Twenty-seven of 39 isolates from Vietnam showed CQ susceptible genotype coding CVMNK, while other 10 did CQ resistance type (CVIET, CVIDT, CVMDT). The other 2 isolates were proved to be mixed with CQ susceptible/resistant.
    In the further analysis of the Vietnam isolates, the MS DNA markers of the CQ susceptible isolates were revealed to be highly polymorphic, while those of CQ resistant isolates were less polymorphic. One of the CQ resistant isolates (CVIET) had a different MS DNA pattern from K1 (CQ resistant strain; CVIET) from Thailand. The other CQ resistant isolate types (CVIDT, CVMDT) shared the same MS DNA patterns and these patterns were different from those of the CQ susceptible isolates nor K1. These results showed that the origin of the CQ resistant isolates in Vietnam might not be due to an introduction of the isolates from Thailand. Instead, it is suggested that the CQ resistant mutations possibly occurred within Vietnam.

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  • マラリア重症化に係わる新規病原因子の探求

    Grant number：16790242  2004 - 2005

    日本学術振興会  科学研究費助成事業  若手研究(B)

    畑生 俊光

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    Grant amount：\3600000 （ Direct expense: \3600000 ）

    本研究年度は、膜結合型ケモカインの一つフラクタルカイン(FKN)に対して熱帯熱マラリア原虫感染赤血球が接着する際に利用する、新規熱帯熱マラリア原虫感染赤血球表面発現蛋白質の同定を試みた。研究方法は、(1)FKN接着熱帯熱マラリア原虫株を確立し、当該原虫株よりcDNAライブラリーを作製し、浮遊細胞株Jurkat株へ遺伝子導入する。その後、作製したcDNA導入細胞株と培養プレート表面にコーティングした組み換えFKN蛋白質(rFKN)との直接接着を観察することで、目的蛋白質をクローニングする。(2)yeast two-hybrid(Y2H)法を利用した蛋白質スクリーニングを行う、の2通りで行った。(1)について、FKN接着株を確立した後、当該原虫株よりcDNAライブラリーを作製した。作製したcDNAライブラリーを2種類の哺乳動物細胞発現ベクターに組み込んだマラリア原虫cDNAライブラリー強制発現ベクターを確立した。これらベクターをFKN受容体の発現がないことを確認した浮遊細胞株Jurkatにリポフェクション法およびエレクトロポレーション法にて遺伝子導入した。当該発現ベクターにはC末端側にGFP遺伝子を組み込んでおり、導入遺伝子産物はGFPとの融合蛋白質として発現される。そこで、導入遺伝子産物の発現はFACScanにて確認した。薬剤選抜後、rFKNとの接着を確認したが、当該細胞株とrFKNとの接着は確認できなかった。現在もスクリーニング継続中である。(2)について、Y2Hにてマラリア原虫cDNAライブラリー産物およびFKNとの相互作用を検討した結果、5個の候補蛋白質が同定された。これらの内、2個の蛋白質は接着関連蛋白質のホモローグであり、3個は未知の蛋白質であることがデータベースとの照合の結果明らかとなった。

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  • 細胞内寄生性原虫の病態形成・重症化機構の解析

    1999

    Grants and Funding 

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    Grant type：Competitive

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  • 細胞内寄生性原虫の病態形成・重症化機構の解析

    1999

    補助金 

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    Grant type：Competitive

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