論文 - 丸山 治彦
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Notch2 signaling is required for proper mast cell distribution andmucosal immunity in the intestine 査読あり
Sakata-Yanagimoto M, Sakai T, Maruyama H, Nakagami-Yamaguchi E, Kumano K, Kuroakwa M, Ogawa S, Yasutomo K, Chiba S
Blood 117 128 - 134 2011年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Transcripts analysis of infective larvae of an intestinal nematode, Strongyloides venezuelensis 査読あり
Yoshida A, Nagayasu E, Nishimaki A, Sawaguchi A, Yanagawa S, Maruyama H
Parasitology International 60 ( 1 ) 75 - 83 2011年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Transcripts analysis of infective larvae of an intestinal nematode, Strongyloides venezuelensis.
Yoshida A, Nagayasu E, Nishimaki A, Sawaguchi A, Yanagawa S, Maruyama H
Parasitology international 60 ( 1 ) 75 - 83 2011年1月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Parasitology International
Free-living infective larvae of Strongyloides nematodes fulfill a number of requirements for the successful infection. They need to endure a long wait in harsh environmental conditions, like temperature, salinity, and pH, which might change drastically from time to time. Infective larvae also have to deal with pathogens and potentially hazardous free-living microbes in the environment. In addition, infective larvae must recognize the adequate host properly, and start skin penetration as quickly as possible. All these tasks are essentially important for the survival of Strongyloides nematodes, however, our knowledge is extremely limited in any one of these aspects. In order to understand how Strongyloides infective larvae meet these requirements, we examined transcripts of infective larvae by randomly sequencing cDNA clones constructed from S. venezuelensis infective larvae. After assembling successfully sequenced clones, we obtained 162 unique singletons and contigs, of which 84 had been significantly annotated. Annotated genes included those for respiratory enzymes, heat-shock proteins, neuromuscular proteins, proteases, and immunodominant antigens. Genes for lipase, small heat-shock protein, globin-like protein and cytochrome c oxidase were most abundantly transcribed, though genes of unknown functions were also abundantly transcribed. There were no hits found against NCBI or NEMABASE4 for 37 (22.3%) EST out of the total 162 EST. Although most of the transcripts were not infective larva-specific, the expression of respiration related proteins was most actively transcribed in the infective larva stage. The expression of astacin-like metalloprotease, small heat-shock protein, S. stercoralis L3Nie antigen homologue, and one unannotated and 2 novel genes was highly specific for the infective larva stage. © 2010 Elsevier Ireland Ltd.
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Zoonotic filariasis caused by Onchocerca dewittei japonica in a resident of Hiroshima Prefecture, Honshu, Japan
Uni S, Boda T, Daisaku K, Ikura Y, Maruyama H, Hasegawa H, Fukuda M, Takaoka H, Bain O.
Parasitology International 59 ( 3 ) 477 - 480 2010年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Uni S., Boda T., Daisaku K., Ikura Y., Maruyama H., Hasegawa H., Fukuda M., Takaoka H., Bain O.
Parasitology International 59 ( 3 ) 477 - 480 2010年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Parasitology International
A female of Onchocerca sp. was found to be the probable causative agent of a subcutaneous nodule in the left knee of a 70-year-old man in a rural area of Hiroshima Prefecture, Honshu, the main island of Japan. We compared the characteristics of the agent with the features of the four previously suspected species found in cattle and horses in various parts of the world, as well as O. lupi and O. jakutensis that were suspected or proved, respectively, in zoonotic cases in Europe. In addition, the morphologic characteristics of this parasite were compared with those of the four Onchocerca species found in wild animals in Japan. Based on such characteristics as the large triangle ridges, the considerable distance between any two adjacent ridges, and the absence of inner cuticular striae in the longitudinal sections, we found the causative agent in the present case to be identical to the female of Onchocerca dewittei japonica. All five previous cases of zoonotic onchocerciasis in Japan had been found in Oita, Kyushu, the main southern island. This human case caused by O. dewittei japonica suggests that zoonotic onchocerciasis is liable to occur in rural areas in Japan where wild boar, Simulium vectors, and humans overlap. © 2010 Elsevier Ireland Ltd.
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Enko K., Tada T., Ohgo K., Nagase S., Nakamura K., Ohta K., Ichiba S., Ujike Y., Nawa Y., Maruyama H., Ohe T., Kusano K.
Circulation Journal 73 ( 7 ) 1344 - 1348 2009年7月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Circulation Journal
A 19-year-old man was transferred to hospital because of myocarditis with cardiogenic shock. Echocardiography showed a left ventricular ejection fraction of 23.8% and an intermediate amount of pericardial effusion. The patient immediately received an intra-aortic balloon pump and percutaneous cardiopulmonary support. Right ventricular endomyocardial biopsy was performed in the acute phase and showed extensive eosinophilic inflammatory cell infiltration, severe interstitial edema and moderate myocardial necrosis. High-dose corticosteroids were administered. Because the patient's antibody titer against Toxocara canis was high and his symptoms had appeared after eating raw deer meat, the diagnosis was fulminant eosinophilic myocarditis caused by a hypersensitivity reaction to visceral larval migrans. After starting high-dose corticosteroids, the ejectionfraction dramatically improved, me eosinophilia decreased and the patient made a full recovery.
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Case of creeping disease treated with ivermectin
Senba Y., Tsuda K., Maruyama H., Kurokawa I., Mizutani H., Taniguchi Y.
Journal of Dermatology 36 ( 2 ) 86 - 89 2009年2月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Dermatology
We report a case of creeping disease treated successfully with ivermectin. A 46-year-old man presented with a 1-month history of pruriginous linear erythema on his right thigh after a visit to Indonesia. Although he had no history of eating raw fish or meat, he walked along the river and in the jungle without wearing shoes. Creeping disease caused by animal hookworm was strongly suspected. The presence of parasite larvae was not confirmed in biopsied skin specimens. In enzyme-linked immunosorbent assay, serum samples were negative for binding to hookworm antigens, including Ancylostoma canium, Necator americanus and Gnathostoma doloresi. He was treated with a single 12 mg oral dose (200 μg/kg) of ivermectin. The eruption and pruritus resolved within a few days after the administration and did not relapse. © 2009 Japanese Dermatological Association.
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A familial case of visceral toxocariasis due to consumption of raw bovine liver.
Yoshikawa M, Nishiofuku M, Moriya K, Ouji Y, Ishizaka S, Kasahara K, Mikasa K, Hirai T, Mizuno Y, Ogawa S, Nakamura T, Maruyama H, Akao N.
Parasitology International 57 525 - 529 2008年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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A familial case of visceral toxocariasis due to consumption of raw bovine liver 査読あり
Yoshikawa M., Nishiofuku M., Moriya K., Ouji Y., Ishizaka S., Kasahara K., Mikasa K., Hirai T., Mizuno Y., Ogawa S., Nakamura T., Maruyama H., Akao N.
Parasitology International 57 ( 4 ) 525 - 529 2008年12月
記述言語：英語 掲載種別：症例報告 出版者・発行元：Parasitology International
We present 3 adult cases of visceral toxocariasis from the same family, who each consumed thin slices of raw bovine liver weekly, and developed eosinophilia and multiple small lesions in their livers and lungs. Serological examinations using the larval excretory-secretory product of Toxocara canis strongly indicated infection with Toxocara species larvae. The patients responded well to treatment with albendazole. Ingestion of raw liver from paratenic animals is considered to be a common transmission route of human toxocariasis, especially in adults. © 2008 Elsevier Ireland Ltd. All rights reserved.
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丸山 治彦
日本薬理学雑誌 132 ( 5 ) 292 - 296 2008年11月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：公益社団法人 日本薬理学会
わが国における寄生虫病・熱帯病治療の問題点は，国内承認薬が少なく，保険適用の効能の範囲も狭いことである．たとえば，重要な熱帯感染症であるマラリアに対してはメフロキンとキニーネ末が承認されているが，重症マラリアには対応できず，三日熱マラリアと卵形マラリアに必要な根治療法もおこなえない．また，近年増加傾向にある赤痢アメーバ症，国内の寄生虫病で比較的多い幼虫移行症に有効な薬剤は，承認されてはいるが効果効能では適用外である．トキソプラズマ症も国内承認薬だけでの治療は困難である．このような問題はあるが，「輸入熱帯病・寄生虫症に対する稀少疾病治療薬を用いた最適な治療法による医療対応の確立に関する研究」班（略称：熱帯病治療薬研究班）が，薬剤の輸入・保管・治療対応に関する研究活動を行っており，国内未承認薬での治療が可能になっている．<br>
DOI： 10.1254/fpj.132.292
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Goblet cell hyperplasia elicited by infection with an intestinal nematode, Strongyloides venezuelensis, is not protective against goblet cell-sensitive Nippostrongylus brasiliensis in mice. 査読あり
Chiyo Yamauchi-Kawaura, Hitomi Watanabe, Anna Nishimaki, Haruhiko Maruyama, Ayako Yoshida, Nobuo Ohta
Nagoya Mecical Journal 49 119 - 129 2008年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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山内(川浦) 稚代, 渡邊 仁美, 西牧 亜奈, 丸山 治彦, 吉田 彩子, 太田 伸生
Nagoya medical journal 49 ( 2 ) 119 - 129 2008年3月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：名古屋市立大学
Intestinal nematode infections usually elicit similar pathological changes in the intestinal mucosa, regardless of the parasite species. Because Th2 cytokines, such as IL-4, IL-5, IL-9, and IL-13, are produced simultaneously, similar cellular responses occur in a number of parasitic infections. In Strongyloides venezuelensis infection in mice, goblet cell hyperplasia was induced after infection as expected. However, the goblet cells induced in S. venezuelensis infection was not protective against another intestinal nematode, Nippostrongylus brasiliensis, whose expulsion was tightly associated with goblet cell hyperplasia. Lectin histochemistry revealed that there was no evidence for the sialation of mucin sugars, although the structure of goblet cell mucin changed after S. venezuelensis infection. Because N. brasiliensis infection induces highly sialated goblet cell mucin, not only Th 2 cytokines but specific factors from N. brasiliensis adult worms might be required for the sialation of intestinal goblet cell mucin.
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Goblet cell hyperplasia elicited by infection with an intestinal nematode, Strongyloides venezuelensis, is not protective against goblet cell-sensitive Nippostrongylus brasiliensis in mice. 査読あり
Chiyo Yamauchi-Kawaura, Hitomi Watanabe, Anna Nishimaki, Haruhiko Maruyama, Ayako Yoshida, Nobuo Ohta
Nagoya Mecical Journal 49 119 - 129 2008年3月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌）
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Successive changes in tissue migration capacityof developing larvae of an intestinal nematode, Strongyloides venezuelensis 査読あり
H. Maruyama, A. Nishimaki, Y. Takuma, M. Kurimoto, T. Suzuki, Y. Sakatoku, M. Ishikawa and N. Ohta
Parasitology 132 411 - 418 2007年4月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Maruyama H., Nawa Y.
No to shinkei. Brain and nerve 58 ( 7 ) 571 - 581 2006年7月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：No to shinkei. Brain and nerve
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Shaohong L., Kumagai T., Qinghua A., Xiaolan Y., Ohmae H., Yabu Y., Siwen L., Liyong W., Maruyama H., Ohta N.
Parasitology International 55 ( 1 ) 63 - 68 2006年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Parasitology International
The therapeutic effects of artesunate against experimental Schistosoma mansoni infection in mice were analyzed. Previous studies showed that artesunate is highly effective against S. japonicum infection, but the action of this drug against S. mansoni remained uncovered. The present study examines the optical conditions for artesunate against S. mansoni and evaluates the effects of inhibiting the sexual maturation of adult worms. Mice infected with S. mansoni were orally administered with artesunate according to different schedules. Four consecutive administrations of 300 mg/kg of artesunate at 2-week intervals conferred almost total protection without the development of pathological lesions in the liver. The significant reduction in the number of eggs produced by surviving worms and the status of egg maturation suggested that artesunate inhibits sexual maturation. Electron microscopy revealed that artesunate caused morphological damage, especially on the worm tegument. Artesunate was also very effective in iron-deficient mice. Furthermore, the efficacy of artesunate was equal to or better than that of artemether against S. japonicum infection. Considering that artemether is more toxic, artesunate is currently one of the most efficient drugs against immature S. mansoni. © 2005 Elsevier Ireland Ltd. All rights reserved.
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Sasaki Y., Yoshimoto T., Maruyama H., Tegoshi T., Ohta N., Arizono N., Nakanishi K.
Journal of Experimental Medicine 202 ( 5 ) 607 - 616 2005年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Experimental Medicine
C57BL/6 (B6) and B6 background STAT6-/- mice pretreated with IL-18 plus IL-2 showed prominent intestinal mastocytosis and rapidly expelled implanted adult worms of the gastrointestinal nematode Strongyloides venezuelensis. In contrast, identically pretreated mast cell-deficient W/W v mice failed to do so. Thus, activated mucosal mast cells (MMC) are crucial for parasite expulsion. B6 mice infected with S. venezuelensis third-stage larvae (L3) completed parasite expulsion by day 12 after infection, whereas IL-18-/- or IL-18Rα-/- B6 mice exhibited marked impairment in parasite expulsion, suggesting a substantial contribution of IL-18-dependent MMC activation to parasite expulsion. Compared with IL-18-/- or IL-18Rα-/- mice, S. venezuelensis L3-infected STAT6-/- mice have poorly activated MMC and sustained infection; although their IL-18 production is normal. Neutralization of IL-18 and IL-2 further reduces expulsion in infected STAT6-/- mice. These results suggest that collaboration between IL-18-dependent and Th2 cell-dependent mastocytosis is important for prompt parasite expulsion. JEM © The Rockefeller University Press.
DOI： 10.1084/jem.20042202
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Schistosoma japonicum: Localization of calpain in the penetration glands and secretions of cercariae 査読あり
Kumagai T., Maruyama H., Hato M., Ohmae H., Osada Y., Kanazawa T., Ohta N.
Experimental Parasitology 109 ( 1 ) 53 - 57 2005年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Experimental Parasitology
A monoclonal antibody was generated against the large subunit of Schistosoma japonicum calpain to study the localization and possible function of the molecule in vivo. Mice were immunized with recombinant S. japonicum calpain and polyclonal antisera and a monoclonal antibody specific to schistosome calpain was obtained. In immunohistochemistry, a monoclonal antibody against S. japonicum calpain, KG-2E11, bound weakly to calpain expressed at the surface of adult worm tegument, however, it bound strongly to the cercarial secretions ("footprints") of S. japonicum, emitted from the penetration glands. The present study indicates that calpain is multifunctional as it is expressed at various locations in different developmental stages. Calpain-based vaccines could thus possibly induce protective immunity against cercariae and the following early developing stages. © 2004 Elsevier Inc. All rights reserved.
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El-Malky M., Shaohong L., Kumagai T., Yabu Y., Noureldin M., Saudy N., Maruyama H., Ohta N.
Microbiology and Immunology 49 ( 7 ) 639 - 646 2005年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Microbiology and Immunology
Infection with the intracellular protozoan parasite Toxoplasma gondii causes serious public health problems to both humans and livestock and of great economic impact worldwide. Oligodeoxynucleotides (ODN) which contain immunostimulatory CG motifs (CpG ODN) can promote Th1 responses, an adjuvant activity that is desirable for vaccination against intracellular pathogens. We investigated the feasibility of using CpG as an adjuvant combined with Toxoplasma lysate antigen (TLA) as a vaccine against toxoplasmosis. Genetically susceptible C57BL/6 mice were vaccinated with TLA with or without CpG ODN as an adjuvant and then challenged with 85 cysts of the moderately virulent RRA (Beverley) strain of T. gondii. Prior to challenge infection, immunization with TLA plus CpG ODN directed cellular and humoral immunity toward a Th1 pattern, characterized by enhanced INFγ production by splenic cells in response to TLA, and enhanced production of toxoplasma-specific IgG and IgG2a antibodies. Consequently, CpG/TLA-treated mice showed prolonged survival and 64% reduction in brain parasite burden compared to non-CpG/TLA treated group. Our results suggest that CpG ODN would provide a stable and effective adjuvant for use in vaccination against toxoplasmosis.
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Hsieh G., Loukas A., Wahl A., Bhatia M., Wang Y., Williamson A., Kehn K., Maruyama H., Hotez P., Leitenberg D., Bethony J., Constant S.
Journal of Immunology 173 ( 4 ) 2699 - 2704 2004年8月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Immunology
Parasitic helminths induce chronic infections in their hosts although, with most human helminthiases, protective immunity gradually develops with age or exposure of the host. One exception is infection with the human hookworm, Necator americanus, where virtually no protection ensues over time. Such observations suggest these parasites have developed unique mechanisms to evade host immunity, leading us to investigate the role of the excretory/secretory (ES) products of adult N. americanus in manipulating host immune responses. Specifically, we found that a protein(s) from ES products of adult N. americanus bound selectively to mouse and human NK cells. Moreover, incubation of purified NK cells with N. americanus ES products stimulated the production of augmented (4- to 30-fold) levels of IFN-γ. This augmentation was dependent on the presence of both IL-2 and IL-12 and was endotoxin-independent. This is the first report of a pathogen protein that binds exclusively to NK cells and the first report of a nematode-derived product that induces abundant levels of cytokines from NK cells. Such an interaction could provide a means of cross-regulating deleterious Th2 immune responses in the host, thereby contributing to the long-term survival of N. americanus.