論文 - 丸山 治彦
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Four successive cases of human fasciolosis in Japan. 査読あり
Kumabe A, Doi A, Kitaura T, Katayama A, Harada T, Ueda M, Matsuda R, Ichikawa-Seki M, Tanaka M, Kaneko C, Yoshida A, Chikumi H, Maruyama H
Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 31 ( 2 ) 102480 2025年2月
担当区分：責任著者 記述言語：英語 掲載種別：症例報告 出版者・発行元：Journal of Infection and Chemotherapy
Fasciolosis is a food-borne parasitic disease, caused by the large liver fluke, Fasciola. Humans acquire infection by ingesting fresh or undercooked water plants, on which infective metacercaria encyst. In spite of the rarity of the disease in Japan, we encountered four successive fasciolosis patients within a short period, who were all living in the same area. The patients were 70–82 years old, three females and the husband of one of the female patients. They started complaining of non-specific symptoms, such as fever, general fatigue, appetite loss, and abdominal pain, almost at the same time. All patients showed prominent peripheral blood eosinophilia, and the medical imaging indicated multiple hepatic lesions. No parasite eggs or worms were detected in any of the patients. Diagnosis was made serologically and they were treated with praziquantel and/or triclabendazole. No cattle or sheep were farmed in the area, but the wild sika deer, Cervus nippon, inhabited adjacent to the residential area. The intermediate host snail, Austropeplea ollula, were found near the residence of the patients, and one of the collected snails was positive for F. hepatica/gigantica hybrid type rediae. Our report should alarm the medical professionals for this rare and unfamiliar parasitic disease.
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Kokubo-Tanaka M, Kildemoes AO, Chadeka EA, Cheruiyot BN, Moriyasu T, Sassa M, Nakamura R, Kikuchi M, Fujii Y, de Dood CJ, Corstjens PLAM, Kaneko S, Maruyama H, Njenga SM, de Vrueh R, Hokke CH, Hamano S
PLoS neglected tropical diseases 19 ( 1 ) e0012813 2025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：PLoS Neglected Tropical Diseases
Background Schistosoma haematobium is the causative pathogen for urogenital schistosomiasis. To achieve progress towards schistosomiasis elimination, there is a critical need for developing highly sensitive and specific tools to monitor transmission in near-elimination settings. Although antibody detection is a promising approach, it is usually unable to discriminate active infections from past ones. Moreover, crude antigens such as soluble egg antigen (SEA) show cross-reactivity with other parasitic infections, and it is difficult to formulate the standard preparations. To resolve these issues, the performances of recombinant antigens have been evaluated. The antibody responses against recombinant S. haematobium ser-ine-protease inhibitor (ShSerpin) and RP26 were previously shown to reflect active schisto-some infection in humans. Furthermore, antibody detection using multiple recombinant antigens has been reported to improve the accuracy of antibody-based assays compared to single-target assays. Therefore, we examined the performances of ShSerpin, RP26 and the mixture of these antigens for detecting S. haematobium low-intensity infection and assessed the potential for transmission monitoring. Methodology/Principal findings We collected urine and plasma samples from school-aged children in Kwale, Kenya and evaluated S. haematobium prevalence by number of eggs in urine and worm-derived circulating anodic antigen (CAA) in plasma. Among 269 pupils, 50.2% were CAA-positive by the lateral flow test utilizing up-converting phosphor particles (UCP-LF CAA), while only 14.1% were egg-positive. IgG levels to S. haematobium SEA (ShSEA), ShSerpin, RP26, and the mixture of ShSerpin and RP26 were measured by ELISA. The mixture of ShSerpin and RP26 showed the highest sensitivity, 88.7%(125/141)among the four antigens in consider-ing indecisive UCP-LF CAA results as negative. Conclusion/Significance IgG detection against the ShSerpin-RP26 mixture demonstrated better sensitivity for detection of active S. haematobium infection. This recombinant antigen mixture is simpler to pro-duce with higher reproducibility and can potentially replace ShSEA in monitoring transmission under near-elimination settings.
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Kounosu A, Sun S, Maeda Y, Dayi M, Yoshida A, Maruyama H, Hunt V, Sugimoto A, Kikuchi T
Philosophical transactions of the Royal Society of London. Series B, Biological sciences 379 ( 1894 ) 20220446 2024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：Philosophical Transactions of the Royal Society B: Biological Sciences
The Strongyloides clade, to which the parasitic nematode genus Strongyloides belongs, contains taxa with diverse lifestyles, ranging from free-living to obligate vertebrate parasites. Reproductive strategies are also diverse in this group of nematodes, employing not only sexual reproduction but also parthenogenesis, making it an attractive group to study genome adaptation to specific conditions. An in-depth understanding of genome evolution, however, has been hampered by fragmented genome assemblies. In this study, we generated chromosome-level genome assemblies for two Strongyloides species and the outgroup species Rhabditophanes diutinus using long-read sequencing and high-throughput chromosome conformation capture (Hi-C). Our synteny analyses revealed a clearer picture of chromosome evolution in this group, suggesting that a functional sex chromosome has been maintained throughout the group. We further investigated sex chromosome dynamics in the lifecycle of Strongyloides ratti and found that bivalent formation in oocytes appears to be important for male production in the mitotic parthenogenesis. This article is part of the Theo Murphy meeting issue 'Strongyloides: omics to worm-free populations'.
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Koga M, Suganuma A, Kikuchi T, Yoshimura Y, Shoji K, Kobayashi I, Takezaki S, Kato Y, Kimura M, Maruyama H, Research Group on Chemotherapy of Tropical Diseases, Japan.
Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 ( 6 ) 924 - 928 2021年6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） 出版者・発行元：Journal of Infection and Chemotherapy
Treatment of intractable Pneumocystis jirovecii pneumonia (PCP) patients with primaquine (PQ) in combination with clindamycin (CLDM) was conducted by the Research Group on Chemotherapy of Tropical Diseases (RG-CTD), as a kind of compassionate use. Primaquine was not nationally licensed at the time but imported by RG-CTD for the use in a clinical research to investigate safety and efficacy in malaria treatment. Eighteen Japanese adult patients thus treated were analyzed. Prior to the treatment with PQ-CLDM, most of the patients had been treated with trimethoprim-sulfamethoxazole first, all of which being followed by pentamidine and/or atovaquone treatment. This combination regimen of PQ-CLDM was effective in 16 (89%) patients and developed adverse events (AEs) in five (28%) patients. AEs included skin lesions, methemoglobinemia, and hepatic dysfunction, though none of them were serious. As a second-line or salvage treatment for PCP, PQ-CLDM appears to be a better option than pentamidine or atovaquone. Currently in Japan, both PQ and CLDM are licensed drugs but neither of them is approved for treatment of PCP. Considering the potentially fatal nature of PCP, approval of PQ-CLDM for treating this illness should be urged.
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Sugiyama T, Ichikawa-Seki M, Sato H, Kounosu A, Tanaka M, Maruyama H
Parasitology international 82 102311 2021年6月
担当区分：最終著者, 責任著者 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
Recombinant Fasciola cathepsin L-1 (rCatL1) was evaluated in enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of human fasciolosis in Japan. Quality characteristics of the test were accessed by receiver operating characteristic (ROC) analysis, with sera from fasciolosis patients (n = 10), patients with no evidence of parasitic infections (n = 29), and patients with other helminth infections (n = 119). Both the sensitivity and specificity of the test achieved 100% with the control samples. To test the performance of the assay in an authentic situation, 311 serum samples, which had been sent to our laboratory for the diagnosis of parasitic infections from January 2018 to February 2019, were re-assessed using the rCatL1 ELISA. In this case, the sensitivity of the rCatL1 ELISA was 100%, giving positive results to all fasciolosis sera (n = 7), and the specificity was 99.0%, in which three of the 304 non-fasciolosis samples were judged positive. Careful re-examination of the laboratory data and medical imaging of these three patients revealed that one of the patients, who had been diagnosed as having larva migrans syndrome, was judged to be infected with Fasciola, in addition to ascarid nematodes. Thus the true specificity of the assay in the authentic reached 99.3% (302/304). As the rCatL1 ELISA exhibited a highly significant positive likelihood ratio (152.0) and negative likelihood ratio (0.0), calculated from the 311 sample data, this rCatL1 ELISA can be used for routine screening and definitive diagnosis test for fasciolosis in reference laboratories.
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Kikuchi T, Dayi M, Hunt VL, Ishiwata K, Toyoda A, Kounosu A, Sun S, Maeda Y, Kondo Y, de Noya BA, Noya O, Kojima S, Kuramochi T, Maruyama H
Communications biology 4 ( 1 ) 649 - 649 2021年5月
担当区分：最終著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Communications Biology
The cryptic parasite Sparganum proliferum proliferates in humans and invades tissues and organs. Only scattered cases have been reported, but S. proliferum infection is always fatal. However, S. proliferum’s phylogeny and life cycle remain enigmatic. To investigate the phylogenetic relationships between S. proliferum and other cestode species, and to examine the mechanisms underlying pathogenicity, we sequenced the entire genomes of S. proliferum and a closely related non–life-threatening tapeworm Spirometra erinaceieuropaei. Additionally, we performed larvae transcriptome analyses of S. proliferum plerocercoid to identify genes involved in asexual reproduction in the host. The genome sequences confirmed that the S. proliferum has experienced a clearly distinct evolutionary history from S. erinaceieuropaei. Moreover, we found that nonordinal extracellular matrix coordination allows asexual reproduction in the host, and loss of sexual maturity in S. proliferum are responsible for its fatal pathogenicity to humans. Our high-quality reference genome sequences should be valuable for future studies of pseudophyllidean tapeworm biology and parasitism.
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Nakagawa Y, Ikematsu Y, Nakanishi T, Ogawa Y, Taen R, Nakashima Y, Okabe H, Yoshida A, Maruyama H
Parasitology international 81 102279 2021年4月
担当区分：最終著者, 責任著者 記述言語：英語 掲載種別：症例報告 出版者・発行元：Parasitology International
We encountered an outbreak of paragonimiasis among Cambodian technical intern trainees (TITs) at a food-processing factory in Fukuoka, Japan. The patients were 20–28 years old, seven females and two males, who had been in Japan for one to four years. All of them had consumed raw or undercooked Japanese mitten crab they purchased at a local grocery store near their training place. CT images showed multiple lesions not only in the lungs but in the extrapulmonary organs as well, such as subcutaneous tissues, abdominal muscles, and mesentery, in most of the patients. Their medical records indicated that all of them acquired infection in Japan, not in Cambodia. Diagnosis was made serologically and the patients were treated with praziquantel successfully. Foreign workers and TITs are increasing in Japan so rapidly, that food borne-infections, including paragonimiasis, should be considered in people from developing countries who have exotic dietary habits.
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Hiraoka T, Cuong NC, Hamaguchi S, Kikuchi M, Katoh S, Anh LK, Anh NTH, Anh DD, Smith C, Maruyama H, Yoshida LM, Cuong DD, Thuy PT, Ariyoshi K
PLoS neglected tropical diseases 14 ( 12 ) e0008937 - 15 2020年12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：PLoS Neglected Tropical Diseases
Background Eosinophilic meningitis (EM) is a rare clinical syndrome caused by both infectious and non-infectious diseases. In tropical pacific countries, Angiostrongylus cantonensis is the most common cause. However, the EM definition varies in the literature, and its relation to parasitic meningitis (PM) remains unclear. Methodology/Principal findings Adult and adolescent patients of 13 years old or above with suspected central nervous system (CNS) infections with abnormal CSF findings were prospectively enrolled at a tertiary referral hospital in Hanoi, Vietnam from June 2012 to May 2014. Patients with EM or suspected PM (EM/PM) were defined by the presence of either ≥10% eosinophils or an absolute eosinophil cell counts of ≥10/mm3 in the CSF or blood eosinophilia (>16% of WBCs) without CSF eosinophils. In total 679 patients were enrolled: 7 (1.03%) had ≥10% CSF eosinophilia, 20 (2.95%) had ≥10/mm3 CSF eosinophilia, and 7 (1.03%) had >16% blood eosinophilia. The patients with ≥10% CSF eosinophilia were significantly younger (p = 0.017), had a lower body temperature (p = 0.036) than patients with ≥10/mm3 CSF eosino-philia among whom bacterial pathogens were detected in 72.2% (13/18) of those who were tested by culture and/or PCR. In contrast, the characteristics of the patients with >16% blood eosinophilia resembled those of patients with ≥10% CSF eosinophilia. We further conducted serological tests and real-time PCR to identify A. cantonensis. Serology or real-time PCR was positive in 3 (42.8%) patients with ≥10% CSF eosinophilia and 6 (85.7%) patients with >16% blood eosinophilia without CSF eosinophils but none of patients with ≥10/mm3 CSF eosinophilia. Conclusions The etiology of PM in northern Vietnam is A. cantonensis. The eosinophil percentage is a more reliable predictor of parasitic EM than absolute eosinophil count in the CSF. Patients with PM may present with a high percentage of eosinophils in the peripheral blood but not in the CSF.
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Human proliferative sparganosis update. 査読あり 国際誌
Kikuchi T, Maruyama H
Parasitology International 75 102036 - 102036 2019年12月
担当区分：最終著者, 責任著者 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
Proliferative sparganosis is one of the most bizarre and mysterious parasitic diseases ever described. The causative parasite is Sparganum proliferum, which is a pseudophyllidean cestode distinct from Spirometra tapeworms. Here we overview this rare but fascinating disease with the all original case reports on human patients published in the last 115 years. Proliferative sparganosis is clearly divided into two disease types, cutaneous and internal proliferative sparganosis. Cutaneous type starts with a skin eruption caused by the dermal invasion of a sparganum. Skin lesion progresses to larger areas of the body if left untreated. Various internal organs and body wall can be eventually affected. The clinical symptoms of patients in this group are very similar to each other. Molecular data suggest that cutaneous proliferative sparganosis is caused by S. proliferum of which genetic variation is limited, regardless of the time or localities of the emergence of patients. Internal proliferative sparganosis, on the other hand, is much more heterogeneous. Some cases show aggressive infection in internal organs, while others show only restricted lesions. Some of the cases that had been cited as proliferative sparganosis in the past literature were removed from the list, because they were judged as cyclophyllidean tapeworm infections. DNA sequencing is mandatory for the definite diagnosis of proliferative sparganosis. The Venezuelan strain of S. proliferum is maintained in experimental mice in Japan, which is fully prepared for the experimental study with advanced technologies in modern molecular biology.
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Treatment of larva migrans syndrome with long-term administration of albendazole. 査読あり
Amy Hombu, Ayako Yoshida, Taisei Kikuchi, Eiji Nagayasu, Mika Kuroki, Haruhiko Maruyama
Journal of microbiology, immunology, and infection 2019年2月
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Venison, another source of Paragonimus westermani infection. 査読あり
Yoshida A, Matsuo K, Moribe J, Tanaka R, Kikuchi T, Nagayasu E, Misawa N, Maruyama H
Parasitology international 65 ( 6 Pt A ) 607 - 612 2016年12月
担当区分：最終著者, 責任著者 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
© 2016 Elsevier Ireland Ltd Paragonimiasis is a typical food-borne parasitic disease, endemic in most parts of Asia, with sporadic case reports from American and African countries. The major source of infection is undercooked freshwater crab or crayfish, though consumption of wild boar meat is also responsible for the infection in Japan, because wild boar is a paratenic host for Paragonimus westermani. Recently, living juveniles of P. westermani were isolated from muscle of a sika deer, Cervus nippon, in Japan, raising the possibility that venison has been another source of infection. In order to clarify the potential contribution of venison consumption t o the occurrence of paragonimiasis, we analysed dietary histories of those paragonimiasis patients in whose diagnoses we were involved between 2001 and 2015. Among 380 patients, freshwater crab had been consumed by 208 patients, wild boar meat by 190, and wild deer meat by 76 patients before the onset of the disease. Overall contribution of wild deer meat was estimated to be 6.8% to 20.0%, although in Oita and Gifu Prefectures, where a substantial proportion of patients had consumed raw venison, the contribution of venison consumption was much higher (27.5 to 62.1% and 42.1 to 78.9% in Oita and Gifu Prefectures, respectively). We demonstrated P. westermani-specific antibodies in the sera of 4 out of 160 sika deer from Gifu Prefecture, strongly suggesting that these deer were infected with P. westermani.
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Karyotype and reproduction mode of the rodent parasite Strongyloides venezuelensis 査読あり 国際共著
Hino A., Tanaka T., Takaishi M., Fujii Y., Palomares-Rius J., Hasegawa K., Maruyama H., Kikuchi T.
Parasitology 141 ( 13 ) 1736 - 1745 2014年11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
Copyright © 2014 Cambridge University Press. Strongyloides venezuelensis is a parasitic nematode that infects rodents. Although Strongyloides species described to date are known to exhibit parthenogenetic reproduction in the parasitic stage of their life cycle and sexual reproduction in the free-living stage, we did not observe any free-living males in S. venezuelensis in our strain, suggesting that the nematode is likely to depend on parthenogenetic reproduction. We confirmed by cytological analysis that S. venezuelensis produces eggs by parthenogenesis during the parasitic stage of its life cycle. Phylogenetic analysis using nearly the full length of 18S and D3 region of 28S ribosomal RNA gene suggested that S. venezuelensis is distantly related to another rodent parasite, namely Strongyloides ratti, but more closely related to a ruminant parasite, Strongyloides papillosus. Karyotype analysis revealed S. venezuelensis reproduces with mitotic parthenogenesis, and has the same number of chromosomes as S. papillosus (2n = 4), but differs from S. ratti (2n = 6) in this regard. These results, taken together, suggest that S. venezuelensis evolved its parasitism for rodents independently from S. ratti and, therefore, is likely to have a different reproductive strategy.
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Maruyama H., Nishimaki A., Takuma Y., Kurimoto M., Suzuki T., Sakatoku Y., Ishikawa M., Ohta N.
Parasitology 132 ( 3 ) 411 - 418 2006年3月
担当区分：筆頭著者, 責任著者 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
Infective larvae of an intestinal nematode, Strongyloides venezuelensis, enter rodent hosts percutaneously, and migrate through connective tissues and lungs. Then they arrive at the small intestine, where they reach maturity. It is not known how S. venezuelensis larvae develop during tissue migration. Here we demonstrate that tissue invasion ability of S. venezuelensis larvae changes drastically during tissue migration, and that the changes are associated with stage-specific protein expression. Infective larvae, connective tissue larvae, lung larvae, and mucosal larvae were used to infect mice by various infection methods, including percutaneous, subcutaneous, oral, and intraduodenal inoculation. Among different migration stages, only infective larvae penetrated mouse skin. Larvae, once inside the host, quickly lost skin penetration ability, which was associated with the disappearance of an infective larva-specific metalloprotease. Migrating larvae had connective tissue migration ability until in the lungs, where larvae became able to settle down in the intestinal mucosa. Lung larvae and mucosal larvae were capable of producing and secreting adhesion molecules. © 2005 Cambridge University Press.
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症例報告 Creeping diseaseの3例
太田 志野, 和田 麻依, 松井 はるか, 田中 美緒, 丸山 治彦, 長谷川 英男, 河原 由恵
臨床皮膚科 79 ( 2 ) 159 - 164 2025年2月
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Serial changes in B-cell subsets and immunoglobulin G4 levels in paragonimiasis. 査読あり
Taku K, Ogata M, Hoshina T, Maruyama H, Yoshida A, Kusuhara K
Pediatrics international : official journal of the Japan Pediatric Society 66 ( 1 ) e15727 2024年1月
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A delayed diagnosis of fascioliasis: The importance of appropriate fecal diagnostic method. 査読あり
Kosaka S, Shimizu S, Nakayamada S, Nawata A, Shimono N, Tanaka M, Maruyama H, Osada Y, Tanaka Y
Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 30 ( 5 ) 454 - 458 2023年11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 Infection and Chemotherapy
Fascioliasis, a zoonotic helminthiasis, occurs sporadically in Japan. In this report, we describe a case of fascioliasis that was initially difficult to diagnose because the fecal examination method was negative for the Fasciola sp. eggs. A 64-year-old man living in Shimonoseki City, Japan, presented with fatigue and anorexia. Laboratory tests showed hepatic dysfunction and eosinophilia. Abdominal dynamic contrast-enhanced computed tomography and magnetic resonance cholangiopancreatography suggested intrahepatic biliary cysts. Thereafter, fever and night sweats persisted, and positron emission tomography and biopsy of the porta hepatis lymph node were performed on suspicion of malignancy. However, histopathological diagnosis found non-specific inflammation. As fascioliasis was suspected due to eosinophilia and the multiple hepatic masses, fecal egg examination was performed by an external private laboratory, which adopted the flotation method and reported the absence of parasite eggs. However, fecal examination was retried in our laboratory using the formalin-ether concentration method, and we detected Fasciola sp. eggs. This case suggests that misdiagnosis may occur depending on the fecal examination method; thus, it is necessary to choose a suitable method for certain parasite species.
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Four cases of gnathostomiasis due to the ingestion of raw Salangichthys microdon. 査読あり
Abe T, Hida T, Kamiya T, Ebata K, Sugita S, Kaneko R, Tanaka M, Maruyama H, Suzuki A, Uhara H
The Journal of dermatology 51 ( 2 ) e59 - e60 2023年10月
担当区分：責任著者 記述言語：英語 掲載種別：症例報告 出版者・発行元：Journal of Dermatology
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Maekawa K, Nagayasu E, Hata Y, Hanamure F, Maruyama H, Yamashita A
Pathology international 73 ( 8 ) 373 - 376 2023年8月
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Ko PP, Haraguchi M, Hara T, Hieu DD, Ito A, Tanaka R, Tanaka M, Suzumura T, Ueda M, Yoshida A, Maruyama H, Nagayasu E
Parasitology international 92 102663 2023年2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
Strongyloides is a genus of parasitic nematodes of vertebrates comprising approximately 50 documented species, each with various host ranges. Among these, three species (S. stercoralis, S. fuelleborni, and S. cebus) are known to infect primate hosts. S. fuelleborni typically infects non-human primates in the Old World. To complement the existing information on the global genetic structure of this species, we conducted a genotyping study of S. fuelleborni samples collected from rhesus macaques in Myanmar, Japanese macaques in Japan, and some zoo-kept primates. This study identified a novel haplotype group in isolates from the Myanmar rhesus macaques. Subsequently, we obtained the complete or nearly complete mitochondrial genome sequences of S. fuelleborni, S. cebus (Strongyloides of New World monkeys), and S. vituli (Strongyloides of cattle). Phylogenetic analysis based on concatenated mitochondrial protein sequences of various Strongyloides species indicated a close relationship between S. fuelleborni, S. vituli and S. papillosus (Strongyloides in sheep and cattle). S. cebus is quite distantly related to both S. fuelleborni and S. stercoralis, which led to the hypothesis that the three primate Strongyloides species evolved independently as parasites of primates.
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臨床的に肝蛭症と診断し，トリクラベンダゾール内服後に抗体が陽転した1例 査読あり
谷口 昌史, 阪上 順一, 原 祐, 服部 知恵, 住吉 翔元, 酒井 浩明, 岡 浩平, 岩井 直人, 辻 俊史, 奥田 隆史, 小牧 稔之, 香川 惠造, 丸山 治彦
感染症学雑誌 97 ( 1 ) 32 - 37 2023年1月
担当区分：最終著者 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：一般社団法人 日本感染症学会
We report the case of a Vietnamese man in his twenties who presented with a few days' history mild fever and severe pain in the right hypochondrium. Laboratory findings showed elevated levels of the hepatobiliary enzymes and marked peripheral blood eosinophilia. Abdominal computed tomography (CT) showed map-like low density areas with unclear boundaries under the liver capsule. Suspecting a parasitic infection, we conducted enzyme linked immunosorbent assay (ELISA) for a panel of parasite antigens, including <i>Fasciola</i> antigen. However, no positive results for any parasites were obtained. Re-examination by contrast-enhanced CT revealed that the hepatic mass had moved and findings suggestive of perihepatic inflammation. Fascioliasis was suspected, and the ELISA for <i>Fasciola</i> antigen was repeated again after a period of time, but the result was again negative. Despite the negative test result, the patient was diagnosed as having fascioliasis, based on the severe pain in the right abdomen, persistent eosinophilia, and mobile liver mass, all of which are characteristic symptoms of fascioliasis. For the treatment with triclabendazole (TCB), he was referred to a hospital in the Research Group on Chemotherapy of Tropical Diseases, Japan, which imports nationally unlicensed medicines, including TCB. After the patient received treatment with TCB (10mg/kg), the symptoms disappeared, and the eosinophil counts decreased. Serological testing at 4 weeks after the TCB administration revealed positive antibody results for crude as well as recombinant <i>Fasciola</i> antigen. Fascioliasis is a relatively rare disease, with only few cases per year reported in Japan. There are no worm eggs in the feces in the acute phase, and serological analysis (such as antibody testing) is the basis for the diagnosis. However, in this case, tests for the <i>fasciola</i> antibody initially remained negative. It should be noted that serological analysis can be negative in the early stage of the disease.
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Sakakura S, Yamaguchi F, Abe T, Cho H, Shimizu S, Mase A, Shikama Y, Maruyama H
Infection and drug resistance 16 2429 - 2432 2023年
記述言語：英語 掲載種別：症例報告 出版者・発行元：Infection and Drug Resistance
The Paragonimus westermani infection is a parasitic foodborne infection that induces systemic symptoms with eosinophilia in humans. Here, we described pneumothorax in addition to pulmonary opacities with eosinophilia in a man with a positive P. westermani serology. He was misdiagnosed with chronic eosinophilic pneumonia (CEP) during the initial phase. Paragonimiasis can share similar clinical findings with CEP in cases where the worm is confined to the lungs. The findings of the current study suggest that paragonimiasis and CEP can be distinguished from each other by the presence of various symptoms. Notably, eosinophilia with pneumothorax should be an important diagnostic factor for paragonimiasis.
DOI： 10.2147/IDR.S402392
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症例 感染源が不明であったドロレス顎口虫による皮膚爬行症の1例 査読あり
熊田 大樹, 猪爪 隆史, 栗田 遼二, 野呂瀬 一美, 彦坂 健児, 丸山 治彦, 松江 弘之
皮膚科の臨床 64 ( 10 ) 1727 - 1730 2022年9月
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症例 抗顎口虫抗体陽性で診断,イベルメクチン内服が奏効したCreeping Diseaseの1例
齋藤 麗子, 太田 瑞穂, 冲津 成実, 徳山 道生, 近藤 章生, 栄枝 重典, 橘 裕司, 石井 則久, 丸山 治彦, 馬渕 智生
皮膚科の臨床 64 ( 6 ) 1129 - 1133 2022年5月
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[Current real-world treatments for Japanese patients with eosinophilic esophagitis].
Fujiwara Y, Tanaka F, Nakata R, Kakiya Y, Yamamura M, Tanoue K, Sawada A, Higashimori A, Nishida Y, Maruyama H, Ominami M, Nadatani Y, Fukunaga S, Otani K, Hosomi S, Kamata N, Nagami Y, Taira K
Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology 119 ( 10 ) 929 - 936 2022年
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大腿に生じたSpirometra decipiensによる孤虫症の1例 査読あり
與語 晶子, 今村 桜子, 永井 貴子, 原田 佳代, 長安 英治, 丸山 治彦, 占部 和敬
西日本皮膚科 83 ( 5 ) 477 - 477 2021年10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：日本皮膚科学会-西部支部
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Takaki Y, Kadekaru S, Takami Y, Yoshida A, Maruyama H, Une Y, Nagayasu E
Parasitology international 84 102399 2021年10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
Strongyloides is a genus of parasitic nematodes of vertebrates that contains over 50 species, each with a variable host range. A recent molecular phylogenetic analysis on this genus showed that Strongyloides spp. from various carnivore hosts form a strongly supported clade together with Strongyloides stercoralis, a major pathogen of humans and dogs (named the “stercoralis/procyonis group”). In the present study, we obtained DNA sequencing data of Strongyloides sp. isolated from an imported meerkat (Suricata suricatta). Based on the phylogenetic analysis, we considered this a new member of the stercoralis/procyonis group. This study represents the first isolation and molecular characterization of a Strongyloides species from hosts belonging to the family Herpestidae (mongooses and meerkat). However, whether the meerkat serves as a natural host of this Strongyloides species remains to be investigated.
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Clinico-radiologic Characteristics of Pulmonary Visceral Larva Migrans Caused by Ascaris suum. 査読あり
Matsumoto N, Tsubouchi H, Setoguchi K, Horiguchi T, Shigekusa T, Tsuchida S, Matsuo A, Oda Y, Yanagi S, Maruyama H, Nakazato M
Internal medicine (Tokyo, Japan) 60 ( 18 ) 2899 - 2903 2021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：Internal Medicine
Objective Visceral larva migrans (VLM) caused by Ascaris suum is a major health problem in pig farming regions. The clinical characteristics of pulmonary VLM caused by A. suum, however, are unclear. We assessed the clinico-radiologic features of this disease. Methods Medical records, including the results of chest radiography and high-resolution computed tomography (HRCT), were retrospectively reviewed from January 2000 through June 2019, at the University of Miyazaki Hospital and Kyoritsuiin Hospital in Miyazaki Prefecture, Japan. Results Seven patients with VLM caused by A. suum were identified. All seven patients had a unique habit of consuming raw foods, such as organic vegetables, chicken, turkey, wild boar, and venison. All but one patient, who had eosinophilic pneumonia with a fever and severe fatigue, had only mild or no respiratory symptoms. All 7 patients had remarkable eosinophilia (median, 1,960/μL) and high serum IgE levels (median, 1,346 IU/mL). Chest HRCT revealed multiple nodules and multiple nodular ground-glass opacities in 57% and 29% of the patients, respectively. The pulmonary lesions were located predominantly in subpleural areas. All seven patients were treated with albendazole, which led to improvement within two to three months. Neither eggs nor parasites were detected in the feces or sputum of any patient. Conclusion Consumption of raw organic vegetables or raw meat is a possible route of A. suum infection. Infected patients exhibit mild respiratory symptoms, and multiple nodules with a halo in the subpleural area are a common finding on chest HRCT. Treatment with albendazole was effective in these cases.
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Tanaka M, Kildemoes AO, Chadeka EA, Cheruiyot BN, Sassa M, Moriyasu T, Nakamura R, Kikuchi M, Fujii Y, de Dood CJ, Corstjens PLAM, Kaneko S, Maruyama H, Njenga SM, de Vrueh R, Hokke CH, Hamano S
Parasitology international 83 102346 2021年8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
Schistosomiasis remains a worldwide public health problem, especially in sub-Saharan Africa. The World Health Organization targets the goal for its elimination as a public health problem in the 2030 Neglected Tropical Diseases (NTDs) Roadmap. Concerted action and agile responses to challenges will be necessary to achieve the targets. Better diagnostic tests can accelerate progress towards the elimination by monitoring disease trends and evaluating the effectiveness of interventions; however, current examinations such as Kato–Katz technique are of limited power to detect light-intensity infections. The point-of-care circulating cathodic antigen (POC-CCA) test shows a higher sensitivity compared to the reference standard, Kato-Katz technique, but it still lacks sufficient sensitivity with low infection intensity. In this study, we examined antibody reactions against recombinant protein antigens; Schistosoma mansoni serine protease-inhibitor (SmSerpin) and RP26, by enzyme-linked immunosorbent assay (ELISA) in plasma samples with light-intensity infection. The sensitivity using the cocktail antigen of recombinant SmSerpin and RP26 showed 83.7%. The sensitivity using S. mansoni soluble egg antigen (SmSEA) was 90.8%, but it showed poor specificity (29.7%), while the cocktail antigen presented improved specificity (61.4%). We conclude that antibody detection to the SmSerpin and RP26 protein antigens is effective to detect S. mansoni light-intensity infections. Our study indicates the potential of detecting antibody against recombinant protein antigens to monitor the transmission of schistosomiasis in low endemicity contexts.
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Tsubokawa D, Kikuchi T, Lee JM, Kusakabe T, Yamamoto Y, Maruyama H
PLoS pathogens 17 ( 6 ) e1009649 2021年6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：PLoS Pathogens
Parasitic helminths can reside in humans owing to their ability to disrupt host protective immunity. Receptor for advanced glycation end products (RAGE), which is highly expressed in host skin, mediates inflammatory responses by regulating the expression of pro-inflammatory cytokines and endothelial adhesion molecules. In this study, we evaluated the effects of venestatin, an EF-hand Ca2+-binding protein secreted by the parasitic helminth Strongyloides venezuelensis, on RAGE activity and immune responses. Our results demonstrated that venestatin bound to RAGE and downregulated the host immune response. Recombinant venestatin predominantly bound to the RAGE C1 domain in a Ca2+-dependent manner. Recombinant venestatin effectively alleviated RAGE-mediated inflammation, including footpad edema in mice, and pneumonia induced by an exogenous RAGE ligand. Infection experiments using S. venezuelensis larvae and venestatin silencing via RNA interference revealed that endogenous venestatin promoted larval migration from the skin to the lungs in a RAGE-dependent manner. Moreover, endogenous venestatin suppressed macrophage and neutrophil accumulation around larvae. Although the invasion of larvae upregulated the abundance of RAGE ligands in host skin tissues, mRNA expression levels of tumor necrosis factor-α, cyclooxygenase-2, endothelial adhesion molecules vascular cell adhesion protein-1, intracellular adhesion molecule-1, and E-selectin were suppressed by endogenous venestatin. Taken together, our results indicate that venestatin suppressed RAGE-mediated immune responses in host skin induced by helminthic infection, thereby promoting larval migration. The anti-inflammatory mechanism of venestatin may be targeted for the development of anthelminthics and immunosuppressive agents for the treatment of RAGE-mediated inflammatory diseases.
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Study Protocol for a Randomized, Double-Blind, Placebo-Controlled, Phase-II Trial: AdrenoMedullin for Ischemic Stroke Study.
Yoshimoto T, Saito S, Omae K, Hattori Y, Fukuma K, Kitamura K, Kakuta R, Kita T, Maruyama H, Yamamoto H, Ihara M
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 30 ( 6 ) 105761 2021年6月
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Nguyen YTH, Nonaka N, Maruyama H, Yoshida A
The Journal of veterinary medical science 83 ( 4 ) 671 - 674 2021年4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 Veterinary Medical Science
This study aimed to evaluate the sampling method for the detection of Ascaris suum larval DNA in chicken livers using real-time PCR. Chickens were inoculated with A. suum eggs of a single dose (Group A) or repeatedly low doses (Group B). White spots (WSs) were continuously observed on liver from day 3 after the last infection in Group B and day 14 in Group A. In Group A, larval DNA was detected in WS lesions (78.6%) at a significantly higher rate than in the remaining tissue samples (31.3%). In conclusion, applying WS lesions to the assay improved the detection rate of A. suum DNA in chicken livers, especially in the case of a single infection.
DOI： 10.1292/jvms.20-0404
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Abdominal paragonimiasis after consumption of wild boar meat. 査読あり 国際誌
Nakashima S, Takajo I, Maruyama H, Nagayasu E
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 105 40 - 41 2021年4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：International Journal of Infectious Diseases
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Surgically resected hepatic mass caused by fascioliasis. 査読あり
Wang H, Itoh S, Matsumoto Y, Nishie A, Kurihara T, Shimagaki T, Nagao Y, Toshima T, Harada N, Kohashi K, Oda Y, Ishigami K, Maruyama H, Yoshizumi T, Mori M
Clinical journal of gastroenterology 14 ( 2 ) 662 - 667 2021年4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：Clinical Journal of Gastroenterology
Fascioliasis is a parasitic infestation caused by the digenetic trematodes Fasciola hepatica and F. gigantica. It is not commonly seen in developed countries, so diagnosis there is always difficult as a result of confusion with other hepatic or biliary disorders. A 56-year-old man presented at our hospital with a hepatic mass that had been inadvertently discovered by ultrasonography. Abdominal computed tomography revealed a multi-cystic lesion distributed along the branch of the right bile duct. Endoscopic retrograde cholangiopancreatography showed serrated changes ranging from the upper level of the common bile duct to the right hepatic bile duct. Eosinophilia was not observed and tumor marker levels were within normal ranges. Following right lobectomy combined with bile duct reconstruction, a histological examination revealed cholangitis with inflammatory cell infiltration accompanied by parasite egg-like structures and Charcot–Leyden crystals. An additional serologic test was positive for F. hepatica antibodies. A diagnosis of fascioliasis was thus confirmed by histopathology and serology. Fascioliasis should be suspected if imaging findings such as multiple small hypodense lesions in the liver are observed, and serologic tests can be useful for differential diagnosis.
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<i>Strongyloides stercoralis</i> colitis in a patient positive for human T-cell leukaemia virus with rheumatoid arthritis during an anti-rheumatic therapy: a case report. 査読あり 国際誌
Hashiba Y, Umekita K, Minami H, Kawano A, Nagayasu E, Maruyama H, Hidaka T, Okayama A
Modern rheumatology case reports 5 ( 1 ) 16 - 21 2021年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
An elderly woman with rheumatoid arthritis (RA) presented with a chief complaint of abdominal pain and diarrhea while undergoing treatment with low-dose corticosteroids and abatacept. Endoscopic and histopathological findings revealed manifestations of ulcerative colitis (UC). An intermediate dose of corticosteroids and 5-aminosalicylic acid were administered. Abatacept was discontinued; the anti-TNF biologic, golimumab, was administered for treatment of both RA and UC. However, colitis worsened in response to this therapeutic regimen. Colonoscopy revealed severe mucosal lesions; larvae were detected in samples taken from multiple shallow mucosal ulcers. The patient was diagnosed with Strongyloides stercoralis colitis based on the results of an anti-parasite antibody test and examination of the larval DNA. Furthermore, serology revealed a positive test for antibodies against human T-cell leukemia virus type 1 (HTLV-1). Immunosuppressive treatment was terminated; ivermectin was administered, which resulted in improvements in colitis symptoms within a few weeks. There are several published reports describing Strongyloides stercoralis colitis as a lethal mimic of UC. Corticosteroid and anti-TNF therapies have been reported as among the major risk factors associated with strongyloidiasis in patients with HTLV-1 infection. Therefore, HTLV-1 and Strongyloides infections may be considered in cases of new-onset gastrointestinal symptoms during immunosuppressive therapy, particularly in HTLV-1-endemic regions.
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A Case of Sparganosis Caused by Spirometra decipiens on the Femur
Yogo S., Imamura S., Nagai K., Harada K., Nagayasu E., Maruyama H., Urabe K.
Nishinihon Journal of Dermatology 83 ( 5 ) 453 - 456 2021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：Nishinihon Journal of Dermatology
63 歳，女性。初診の 3 カ月程前から出現した左大腿の皮下結節を主訴に当科を紹介され受診した。初診時，左大腿内側に紫斑とその直下に 1 cm 程の皮下硬結を触れ，超音波検査では肉芽腫が疑われた。切除生検を行ったところ，病理組織検査で寄生虫が確認され，類結核性肉芽腫が真皮から皮下にかけてみられた。寄生虫は，DNA 検査の結果 <i>Spirometra decipiens</i> と同定された。<i>Spirometra decipiens</i> は，マンソン孤虫症の原因であるマンソン裂頭条虫とは異なる孤虫であり，今後広く認知されることが期待される。
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Aye KM, Nagayasu E, Nyunt MH, Zaw NN, Thant KZ, Kyaw MP, Maruyama H
BMC infectious diseases 20 ( 1 ) 906 - 906 2020年11月
担当区分：最終著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：BMC Infectious Diseases
Backgrounds: Primary infection with Toxoplasma gondii during pregnancy can pose serious health problems for the fetus. However, the epidemiological status of toxoplasmosis among reproductive-aged population in Myanmar is largely unknown. Although luciferase immunoprecipitation system (LIPS) assays for serodiagnosis of toxoplasmosis was developed mostly using mouse infection model, had not been tested by using field-derived human samples. Methods: A total of 251 serum samples were collected from reproductive-aged women, residing in Shwegyin township, Bago region, Myanmar and analyzed with a commercial ELISA kit, as well as in-house LIPS assays. Results: The overall seroprevalence for Toxoplasma gondii infection by the commercial ELISA was 11.5%. No clear risk factor was identified except for being in the younger age group (15–30 years old). Overall, LIPS assays showed low sensitivity when the commercial ELSA was used as a reference test. Conclusion: We identified the epidemiological situation of toxoplasmosis in some rural communities in Myanmar. The data obtained here will serve as a primary information for the effort to reduce toxoplasmosis in this region. Although looked promising in the previous experiments with mouse infection model, we found that the reported LIPS procedures need further improvements to increase the sensitivities.
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Phylogenetic relationships of Strongyloides species in carnivore hosts. 査読あり 国際共著 国際誌
Ko PP, Suzuki K, Canales-Ramos M, Aung MPPTHH, Htike WW, Yoshida A, Montes M, Morishita K, Gotuzzo E, Maruyama H, Nagayasu E
Parasitology international 78 102151 - 102151 2020年10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
Strongyloides stercoralis is a parasitic nematode and a major pathogen responsible for human strongyloidiasis. The presence of this species in the dog population has led to an interest in studying the phylogenetic relationships among Strongyloides spp. in carnivore hosts. In the present study, Strongyloides spp. from various carnivore hosts (raccoon, Japanese badger, Siberian weasel, raccoon dog, masked palm civet, and domestic cat) were sought. Except for civets, Strongyloides spp. were identified in all host species. Based on 18S rDNA sequences, nine OTUs (operational taxonomy units) were identified. Molecular phylogenetic analyses using 18S[sbnd]28S rDNA and mitochondrial cox1 (cytochrome c oxidase subunit 1) sequences clustered them into two groups. The first group (named the stercoralis/procyonis group) was comprised of six OTUs and occurred in cats, raccoon dogs, raccoons (S. procyonis), Siberian weasels, and Japanese badgers and included S. stercoralis from humans and dogs. The second group (named the planiceps group) was made up of Strongyloides spp. from raccoon dogs (two OTUs) and one OTU from Siberian weasels. Subsequent analysis using almost the full-length nucleotide sequences of protein-coding genes in their mitochondrial genomes placed Strongyloides spp. of cats in a sister taxon position to S. stercoralis, whereas S. procyonis from raccoons was more distantly related to them. The presence of Strongyloides spp. from various carnivore hosts, which are close relatives of S. stercoralis, suggests this group of Strongyloides (the stercoralis/procyonis group) essentially evolved as parasites of carnivores, although more data on Strongyloides spp. from primate hosts are needed.
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A case of seronegative longitudinally extensive transverse myelitis with possible neuro sweet disease. 査読あり
Toko M, Nezu T, Ueno H, Kamimura T, Aoki S, Hosomi N, Maruyama H
eNeurologicalSci 18 100227 2020年3月
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我が国における妊婦マラリアの検討 査読あり
古賀 道子, 木村 幹男, 長谷川 千尋, 武藤 義和, 忽那 賢志, 加藤 康幸, 丸山 治彦
感染症学雑誌 94 ( 2 ) 254 - 255 2020年3月
担当区分：最終著者 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：(一社)日本感染症学会
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Comparison of a 22-gauge Franseen-tip needle with a 20-gauge forward-bevel needle for the diagnosis of type 1 autoimmune pancreatitis: a prospective, randomized, controlled, multicenter study (COMPAS study).
Kurita A, Yasukawa S, Zen Y, Yoshimura K, Ogura T, Ozawa E, Okabe Y, Asada M, Nebiki H, Shigekawa M, Ikeura T, Eguchi T, Maruyama H, Ueki T, Itonaga M, Hashimoto S, Shiomi H, Minami R, Hoki N, Takenaka M, Itokawa Y, Uza N, Hashigo S, Yasuda H, Takada R, Kamada H, Kawamoto H, Kawakami H, Moriyama I, Fujita K, Matsumoto H, Hanada K, Takemura T, Yazumi S
Gastrointestinal endoscopy 91 ( 2 ) 373 - 381.e2 2020年2月
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寄生虫症抗体検査のこれまでとこれから
丸山治彦
Clinical Parasitology 2019年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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寄生虫症抗体検査のこれまでとこれから
丸山治彦
Clinical Parasitology 2019年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Establishment of a serodiagnosis system for the detection of Toxocara spp. and Ascaris suum infection in chickens. 査読あり 国際共著 国際誌
Nguyen YTH, Hayata Y, Sonoda S, Nonaka N, Maruyama H, Yoshida A.
Parasitology International 75 102022 - 102022 2019年11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
Chickens are considered to act as paratenic hosts for agents, Toxocara canis, T. cati and Ascaris suum; which cause ascarid larva migrans syndrome (ascarid LMS) in humans. In addition, they are the definitive host for Ascaridia galli, considered not to be infective for humans. All ascarid parasites can have a high homology of antigenicity, leading to cross-reactivity in serodiagnostic assays. This study was conducted to establish a procedure for the serological detection of those roundworm infections in chickens. Twenty-five male Julia chickens were divided into five groups (n = 5); T. canis-, T. cati-, Ascaris suum- and Ascaridia galli-infected, and an uninfected control group. In Ascaris suum-soluble worm antigen preparation (As-SWAP) ELISA, all infected groups showed an elevation of anti-ascarid antibodies, indicating the usefulness of As-SWAP as a screening antigen for the detection of ascarid infections. For infecting species identification, T. canis-excretory/secretory (Tc-ES) and Ascaris suum-ES (As-ES) antigen ELISA were conducted by serial dilution sera. Toxocara spp.-infected sera showed stronger binding to Tc-ES than As-ES, while Ascaris suum and Ascaridia galli-infected sera bound to As-ES more strongly than Tc-ES. To discriminate between Ascaris suum and Ascaridia galli infection, sera were pre-incubated with Ascaridia galli-SWAP antigen and applied to Tc-ES and As-ES ELISAs. In this pre-adsorbed ES antigen ELISAs, only the Ascaris suum infected group showed positive binding to As-ES, resulting from the adsorption of cross-reactive antibodies in Ascaridia galli-infected sera. Finally, anti-Toxocara specific antibodies were confirmed by Tc-ES western blot (WB). Toxocara spp.-infected sera showed toxocariasis-specific band pattern in Tc-ES WB, while no specific band appeared on any strip incubated with Ascaris suum, Ascaridia galli-infected and uninfected sera. In conclusion, the serodiagnostic assays evaluated in this study are useful for the detection of ascarid infections in chickens.
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Paragonimus and paragonimiasis in Asia: An update. 査読あり
Yoshida A, Doanh PN, Maruyama H.
Acta Tropica 2019年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Characterization of the RAGE-binding protein, Strongyloides venestatin, produced by the silkworm-baculovirus expression system. 査読あり
Tsubokawa D, Lee JM, Hatta T, Mikami F, Maruyama H, Arakawa T, Kusakabe T, Tsuji N.
Infection, Genetics and Evolution 2019年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Improved 18S and 28S rDNA primer sets for NGS-based parasite detection. 査読あり
Kounosu A, Murase K, Yoshida A, Maruyama H, Kikuchi T.
Scientific Reports 2019年10月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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First molecular identification of Strongyloides vituli in cattle in Japan and insights into the evolutionary history of Strongyloides parasites of ruminants. 査読あり
Ko, P.P., Sakaguchi, K., Yoshida, A., Maruyama, H., Nonaka, N., Nagayasu E.
Parasitology International 2019年10月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Sequential Changes in the Host Gut Microbiota During Infection With the Intestinal Parasitic Nematode Strongyloides venezuelensis. 査読あり
Afrin T., Murase K., Kounosu A., Hunt V., Bligh M., Maeda Y., Hino A., Maruyama H., Tsai I., Kikuchi T.
Frontiers in Cellular and Infection Microbiology 2019年6月
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Maeda Y., Palomares-Rius J., Hino A., Afrin T., Mondal S., Nakatake A., Maruyama H., Kikuchi T.
Parasites and Vectors 12 ( 1 ) 21 2019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：Parasites and Vectors
© 2019 The Author(s). Background: Parasites excrete and secrete a wide range of molecules that act as the primary interface with their hosts and play critical roles in establishing parasitism during different stages of infection. Strongyloides venezuelensis is a gastrointestinal parasite of rats that is widely used as a laboratory model and is known to produce both soluble and insoluble (adhesive) secretions during its parasitic stages. However, little is known about the constituents of these secretions. Results: Using mass spectrometry, we identified 436 proteins from the infective third-stage larvae (iL3s) and 196 proteins from the parasitic females of S. venezuelensis. The proteins that were secreted by the iL3s were enriched with peptidase activity, embryo development and the oxidation-reduction process, while those of the parasitic females were associated with glycolysis, DNA binding (histones) and other unknown functions. Trypsin inhibitor-like domain-containing proteins were identified as the main component of the adhesive secretion from parasitic females. An absence of secretion signals in many of the proteins indicated that they are secreted via non-classical secretion pathways. Conclusions: We found that S. venezuelensis secretes a wide range of proteins to establish parasitism. This includes proteins that have previously been identified as being involved in parasitism in other helminths as well as proteins that are unique to this species. These findings provide insights into the molecular mechanisms underlying Strongyloides parasitism.
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Prevalence and associated risk factors of Strongyloides stercoralis infection in Lower Myanmar. 査読あり
Aung M., Hino A., Oo K., Win K., Maruyama H., Htike W., Nagayasu E.
Tropical medicine and Health 46 ( 1 ) 43 2018年12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：Tropical Medicine and Health
© 2018 The Author(s). Background: Strongyloidiasis is prevalent in Southeast Asian regions along with other soil-transmitted helminthiases, but only limited present-day data was available for Myanmar. Methods: A prevalence survey for Strongyloides stercoralis infection was conducted among villagers in rural areas of three townships located in the Lower Myanmar during 2014-2016 by agar plate culture method in combination with specific identification by molecular assays. Risk factors associated with S. stercoralis infection were assessed by analyzing questionnaires obtained from study participants. Results: Strongyloides stercoralis was identified in 40 out of 703 participants (5.7% overall prevalence). The highest prevalence (14.4%) was observed in Htantabin, while other two communities (Thabaung and Thanlyin) had much lower prevalence (2.2 and 2.5%, respectively). Infection was relatively rare (1.2%) in younger generations under 20 years compared to older generations (9.5%). Even in Htantabin, none of the female residents under age 40 (n = 33) had infection. In adult Htantabin residents, those who answered that they do not wear shoes regularly had an elevated risk of infection (odds ratio = 2.50, 95% confidence interval = 1.03-6.08). Conclusions: This study showed that there is still an on-going transmission of strongyloidiasis in Lower Myanmar. It is highly desirable that the soil should be free of fecal contamination by improving the management of fecal waste. Meanwhile, health education to promote shoe-wearing would be beneficial to reduce the risk of transmission, especially for those who have frequent and intense contact with soil.
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ヒトとイヌに由来するStrongyloides stercoralisの分子系統解析
長安英治, 丸山治彦
Clinical Parasitology 2018年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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ヒトとイヌに由来するStrongyloides stercoralisの分子系統解析
長安英治, 丸山治彦
Clinical Parasitology 2018年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Takotsubo cardiomyopathy associated with Paragonimiasis westermani. 査読あり
Matsuoka R, Muneuchi J, Nagatomo Y, Shimizu D, Okada S, Iida C, Shirouzu H, Watanabe M, Takahashi Y, Maruyama H
Paediatrics and international child health 38 ( 4 ) 302 - 307 2018年11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：Paediatrics and International Child Health
© 2017, © 2017 Informa UK Limited, trading as Taylor & Francis Group. An 11-year-old boy collapsed during morning assembly at his junior high school. The automated external defibrillator detected ventricular fibrillation and provided shock delivery. He was successfully resuscitated and reverted to sinus rhythm. Electrocardiography showed ST-T elevation in the precordial leads. Echocardiography and angiography demonstrated akinesia of the apex and mid-wall of the left ventricle with preserved contraction of the basal segments, which suggested Takotsubo cardiomyopathy. The patient and his family had often eaten uncooked crab, and his father had a past history of infection with Paragonimiasis westermani. The patient had had a persistent cough and chest pain for several weeks. Chest radiograph showed cystic cavities in the left upper lung. Microbiological examination of the sputum demonstrated an egg of P. westermani and immunological assay showed a raised antibody titre to P. westermani. On the12th day of admission, he developed seizures, and magnetic resonance imaging demonstrated cerebral involvement. After the administration of praziquantel for 3 days, the clinical manifestations improved immediately, and echocardiography normalised within 3 weeks. The patient was discharged on the 32nd day + and follow-up was normal. Takotsubo cardiomyopathy following a potentially fatal arrhythmia is a rare cardiac complication associated with pulmonary and central nervous system infection by P. westermani.
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Evaluation of LIPS (luciferase immunoprecipitation system) for serodiagnosis of Toxoplasmosis. 査読あり
Aye, K.M., Nagayasu, E., Baba, M., Yoshida, A., Takashima, Y., Maruyama, H.
Journal of immunological methods 462 91 - 100 2018年11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 Immunological Methods
© 2018 Elsevier B.V. Development of reliable, quantitative technologies for serodiagnosis of Toxoplasma gondii infection remains desirable. The luciferase immunoprecipitation system (LIPS) is a relatively simple, highly sensitive, and rapid quantitative immunoassay. The major advantages of this assay over ELISA are a wider dynamic range, shorter overall assay time, and less sample volume. In this study, we aimed to use this method for the serodiagnosis of toxoplasmosis. Recombinant Toxoplasma antigens (dense granule antigens GRA6, GRA7, and GRA8 and bradyzoite antigen BAG1) fused with nanoluciferase (Nluc, a small luciferase enzyme) were expressed in Escherichia coli, purified, and tested in LIPS assays with sera from experimental mice infected with T. gondii and a WHO standard anti-Toxoplasma human immunoglobulin (TOXM). In the experimentally infected mice, LIPS assays detected antibodies against Nluc-GRA6, Nluc-GRA7, and Nluc-GRA8 as early as day 14, whereas antibodies against Nluc-BAG1 remained undetected until day 21 and then showed significant elevation on day 60. In TOXM sera, LIPS assays with each Nluc recombinant protein produced reliable standard curves with a coefficient of determination (R 2 ) of 0.980–0.989 for GRA6, 0.986–0.990 for GRA7, 0.998–0.999 for GRA8, and 0.942–0.987 for BAG1. The detection limits were estimated to be 3.9, 2, 1, and 1 IU/ml for rGRA6, rGRA7, rGRA8, and rBAG1, respectively. The LIPS assay for toxoplasmosis could detect antibodies against T. gondii in the mouse and human sera with a reasonably high sensitivity. We consider the LIPS assay to be a promising alternative tool for screening, diagnosing, and monitoring toxoplasmosis. In particular, detection of antibodies against BAG1 may be useful for a longitudinal seroprevalence study in suspected high-risk areas on the basis of its elevated serum concentration in the chronic phase.
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Cerebral Paragonimiasis With Hemorrhagic Stroke in a Developed Country. 査読あり
Kashida Y, Niiro M, Maruyama H, Hanaya R
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 27 ( 10 ) 2648 - 2649 2018年10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 Stroke and Cerebrovascular Diseases
© 2018 Elsevier Ltd Paragonimiasis is a food-borne parasitic disease caused by Paragonimus lung flukes, which are epidemic in Asia. Cerebral paragonimiasis accounts for <1% of symptomatic paragonimiasis but is the most common extrapulmonary infection. Cerebral paragonimiasis often mimics stroke and sometimes causes severe neurological sequelae. A 61-year-old woman was admitted to the hospital for severe headache. A head computed tomography scan revealed intracerebral hemorrhage with subarachnoid hemorrhage. The patient also had lesions in the lungs. She frequently ate Japanese mitten crab. Peripheral blood examination results of increased eosinophilia and immunological testing results confirmed the diagnosis of Paragonimus westermani infection. The patient was successfully treated with praziquantel as the first-line agent. Cerebral paragonimiasis is currently rare in developed countries; however, it is an important disease to consider.
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Ohno T, Kai T, Miyasaka Y, Maruyama H, Ishih A, Kino H
Parasitology international 67 ( 4 ) 357 - 361 2018年8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
© 2018 Elsevier B.V. Hymenolepis diminuta is a parasitic tapeworm of the rat small intestine and is recognized as a useful model for the analysis of cestode-host interactions. In this study, we analyzed factors affecting the biomass of the tapeworm through use of rat strains carrying genetic mutations, namely X-linked severe combined immunodeficiency (xscid; T, B and NK cells deficiency), nude (rnu; T cell deficiency), and mast cell deficient rats. The worm biomass of F344-xscid rats after infection with 5 cysticercoids was much larger than control F344 rats from 3 to 8 weeks. The biomass of F344-rnu rats was also larger than the controls, but was intermediate between F344-xscid and control rats. These observations demonstrated that host immunity can control the maximal tapeworm biomass, i.e., carrying capacity, of the rat small intestine. Both T cell and other immune cells (B and NK cells) have roles in determining the carrying capacity of tapeworms. Total worm biomass and worm numbers in mast cell deficient rats (WsRC-Ws/Ws) were not significantly different from control WsRC-+/+ rats after 3 and 6 weeks of primary infection. Mast cell deficient rats displayed reinfection resistance for worm biomass but not worm expulsion. These findings suggest that the mast cell has a role for controlling the biomass of this tapeworm in reinfection alone, but does not affect the rate of worm expulsion. Overall, our findings indicate that the mast cell is not a major effector cell for the control of the carrying capacity of tapeworms. The identity of the major effector cell remains unknown.
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Wang, Z., Shibata, M., Nguyen, Y.T.H., Hayata, Y., Nonaka, N., Maruyama, H., Yoshida, A.
Parasitology international 67 ( 5 ) 622 - 626 2018年6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
© 2018 Elsevier B.V. Ascarid Larva Migrans Syndrome (ascarid LMS) is a clinical syndrome in humans, caused by the migration of animal roundworm larvae such as Toxocara canis, Toxocara cati and Ascaris suum. Humans may acquire infection by ingesting embryonated eggs, or infective larvae of these parasites in contaminated meat and organ meats. To detect these pathogenic contaminations, a novel nested multiplex PCR system was developed. Our novel nested multiplex PCR assay showed specific amplification of T. canis, T. cati and Ascaris spp. Detection limit of the nested multiplex PCR was tested with serial dilution of T. canis, T. cati or A. suum genomic DNA (gDNA) from 100 pg to 100 ag and found to be 10 fg, 1 fg and 100 fg, respectively. When larvae were spiked into chicken liver tissue, DNA of T. canis and A. suum was detected from the liver spiked with a single larva, while the assay required at least 2 larvae of T. cati. Moreover, the ascarid DNA was detected from the liver of mice infected with 100 and 300 eggs of T. canis, T. cati or A. suum. This nested multiplex PCR assay could be useful for the detection of contamination with ascarid larvae in meat and organ meats.
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Nakamura-Uchiyama F, Katanami Y, Kikuchi T, Takaya S, Kutsuna S, Kobayashi T, Mizuno Y, Hasegawa T, Koga M, Yoshimura Y, Hasegawa C, Kato Y, Kimura M, Maruyama H, Research Group on Chemotherapy of Tropical Diseases, Japan.
Travel medicine and infectious disease 22 40 - 45 2018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：Travel Medicine and Infectious Disease
© 2018 Elsevier Ltd Background: The Research Group on Chemotherapy of Tropical Diseases, Japan, introduced artemether–lumefantrine (AL) in late 2002, mainly for treating uncomplicated Plasmodium falciparum malaria. Because AL was on the market in Japan in March 2017, the effectiveness and safety of AL were analyzed to help medical personnel use AL optimally. Methods: Case report forms submitted by the attending physicians were analyzed. When necessary, direct contact with the attending physicians was made to obtain detailed information. Results: Effectiveness analysis was performed for 62 cases and safety analysis was performed for 66 cases. In P. falciparum malaria, the overall cure rate was 91.1% (51/56), of which the cure rates for Japanese and non-Japanese patients were 82.1% (23/28) and 100% (28/28), respectively. The successfully treated cases included severe P. falciparum malaria, with parasite densities exceeding 500,000/μL. Adverse events were reported in 14 patients, including delayed hemolytic anemia which occurred in the top four highest parasitemic cases. Conclusions: AL treatment failure in P. falciparum malaria may not be rare among non-immune individuals, including Japanese. The possibility of delayed hemolytic anemia, which occurs preferentially in high parasitemic cases, should be considered following AL treatment.
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Hasegawa C, Kudo M, Maruyama H, Kimura M
Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 24 ( 3 ) 216 - 219 2018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：Journal of Infection and Chemotherapy
© 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases Delayed haemolytic anaemia has been reported in association with intravenous artesunate treatment in patients with severe Plasmodium falciparum malaria, and furthermore, oral artemisinin-based combination therapies including artemether-lumefantrine (AL) have also been incriminated. However, definite cases of delayed haemolytic anaemia associated with AL appear to be scarce, as reported cases were often treated concomitantly with other anti-malarials. In this study, we report a severe case of delayed haemolytic anaemia following AL alone in a Japanese traveller with severe parasitaemia caused by numerous P. falciparum parasites and a few P. vivax parasites. We also stress the need by further studies to differentiate between delayed haemolytic anaemia and blackwater fever, the latter being another malaria-related haemolytic condition, more clearly than they are now.
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Nagayasu E., Aung M., Hortiwakul T., Hino A., Tanaka T., Higashiarakawa M., Olia A., Taniguchi T., Win S., Ohashi I., Odongo-Aginya E., Aye K., Mon M., Win K., Ota K., Torisu Y., Panthuwong S., Kimura E., Palacpac N., Kikuchi T., Hirata T., Torisu S., Hisaeda H., Horii T., Fujita J., Htike W., Maruyama H.
Scientific reports 7 ( 1 ) 4844 2017年12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：Scientific Reports
© 2017 The Author(s). Humans and dogs are the two major hosts of Strongyloides stercoralis, an intestinal parasitic nematode. To better understand the phylogenetic relationships among S. stercoralis isolates infecting humans and dogs and to assess the zoonotic potential of this parasite, we analyzed mitochondrial Cox1, nuclear 18S rDNA, 28S rDNA, and a major sperm protein domain-containing protein genes. Overall, our analyses indicated the presence of two distinct lineages of S. stercoralis (referred to as type A and type B). While type A parasites were isolated both from humans and dogs in different countries, type B parasites were found exclusively in dogs, indicating that the type B has not adapted to infect humans. These epidemiological data, together with the close phylogenetic relationship of S. stercoralis with S. procyonis, a Strongyloides parasite of raccoons, possibly indicates that S. stercoralis originally evolved as a canid parasite, and later spread into humans. The inability to infect humans might be an ancestral character of this species and the type B might be surmised to be an origin population from which human-infecting strains are derived.
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小腸アニサキス症の2例
森紘一朗，佐原利典，藤田裕晃，中村（内山）ふくみ，大西健児，丸山治彦
Clinical Parasitology 2017年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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熱帯病治療薬研究班の登録患者からみたわが国の輸入熱帯病・寄生虫症の動向
丸山治彦，加藤康幸，古賀道子，菊地 正，木村幹男，熱帯病治療薬研究班
Clinical Parasitology 2017年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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熱帯病治療薬研究班の登録患者からみたわが国の輸入熱帯病・寄生虫症の動向
丸山治彦，加藤康幸，古賀道子，菊地 正，木村幹男，熱帯病治療薬研究班
Clinical Parasitology 2017年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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小腸アニサキス症の2例
森紘一朗，佐原利典，藤田裕晃，中村（内山）ふくみ，大西健児，丸山治彦
Clinical Parasitology 2017年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Uni S, Fukuda M, Ogawa K, Lim YA, Agatsuma T, Bunchom N, Saijuntha W, Otsuka Y, Bhassu S, Mat Udin AS, Zainuri NA, Omar H, Nakatani J, Matsubayashi M, Maruyama H, Ramli R, Azirun MS, Takaoka H
Parasitology international 66 ( 5 ) 593 - 595 2017年10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
© 2017 Elsevier B.V. An 11-year-old boy living in Otsu City, Shiga Prefecture, Kansai Region, Western Honshu, Japan had zoonotic onchocercosis. The patient developed a painful swelling on the little finger of his left hand. The worm detected in the excised mass had external transverse ridges but did not have inner striae in the cuticle. On the basis of the parasite's histopathological characteristics, the causative agent was identified as a female Onchocerca dewittei japonica (Spirurida: Onchocercidae). The species of the filarial parasite was confirmed by sequencing the cox1 gene of the parasite. The Japanese wild boar Sus scrofa leucomystax is a definitive host for O. dewittei japonica, which is then transmitted by blackflies as the vector to humans. The current case described occurred in the Kansai Region, Western Honshu, where such infections were previously not reported.
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糞線虫症研究の新展開
長安英治, 菊池泰生, 丸山治彦
医学と薬学 2017年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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糞線虫症研究の新展開
長安英治, 菊池泰生, 丸山治彦
医学と薬学 2017年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Imported malaria in pregnant women experienced in Japan. 査読あり
Kimura M, Koga M, Hasegawa C, Mutoh Y, Kato Y, Maruyama H.
J Infect Chemother. 23 ( 8 ) 545 - 549 2017年8月
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Daigo Tsubokawa, Takeshi Hatta, Taisei Kikuchi, Hiroki Maeda, Fusako Mikami, M Abdul Alim, Haruhiko Maruyama, Naotoshi Tsuji
International journal for parasitology 47 ( 8 ) 501 - 509 2017年7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：International Journal for Parasitology
© 2017 Australian Society for Parasitology The secretory EF-hand Ca ++ -binding proteins act as calcium signaling molecules for control of cell functions, but those proteins from parasitic helminths are poorly understood. Here, we have identified and characterized an EF-hand Ca ++ -binding protein from the rodent nematode, Strongyloides venezuelensis, termed ‘venestatin’, which is highly conserved in Strongyloides spp. Canonical two EF-hand domains and a signal peptide are present in venestatin. A gel mobility shift assay and Ruthenium red staining indicated that the recombinant venestatin possesses binding ability with Ca ++ ions. Endogenous venestatin was seemingly localized in the hypodermis and gut of the worms and was found in the excretory-secretory products. Quantitative reverse transcription-PCR data showed that venestatin-specific transcript was upregulated in the parasitic stages of S. venezuelensis, and the upregulation occurred promptly after larval invasion through the host's skin, but not in the case of in vitro incubation. Immunization of mice with recombinant venestatin caused a 55% reduction in larval migration to the lungs, and lung hemorrhaging was mild compared with non-immunized groups, suggesting that anti-venestatin sera may interfere with larval migration from skin to lung. Our results suggest that venestatin is secreted from the hypodermis and gut of S. venezuelensis, and has pivotal roles in larval migration.
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Tsuchido Y, Nakamura-Uchiyama F, Toyoda K, Iwagami M, Tochitani K, Shinohara K, Hishiya N, Ogawa T, Uno K, Kasahara K, Ouji Y, Kano S, Mikasa K, Shimizu T, Yoshikawa M, Maruyama H
The American journal of tropical medicine and hygiene 96 ( 5 ) 1185 - 1189 2017年5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：American Journal of Tropical Medicine and Hygiene
Copyright © 2017 by The American Society of Tropical Medicine and Hygiene. Recently, reports of delayed hemolytic anemia after treatment with artemisinin and its derivatives have emerged. Here we report two cases of delayed hemolytic anemia in a patient with severe falciparum malaria after treatment with oral artemether-lumefantrine (AL). The first patient, a 20-year-old Japanese male student, was diagnosed with falciparum malaria and was administered AL. As having a high parasitemia rate (20.6%) was the only severe malaria criterion met in this case and his general condition was stable, we continued with AL treatment. Despite disappearance of malarial parasites after 4 days of AL administration, a persistent fever remained. On days 13 and 16, a diagnosis of hemolytic anemia was made (lactate dehydrogenase [LDH]: 1,466 U/L, hemoglobin [Hb] : 7.2 g/dL). A blood smear at that time revealed no parasites. He recovered naturally from delayed hemolysis. The second patient, a 27-year-old Japanese female student, was diagnosed with falciparum malaria (parasitemia: 4.5%) and treated initially with oral quinine hydrochloride and doxycycline. The following day, parasitemia increased to 7.9% and oral AL was initiated. She was discharged on day 4 after achieving parasite clearance and afebrility. However, on day 5, fever (body temperature > 38C) recurred, and on day 11, a diagnosis of hemolytic anemia was made (LDH: 712 U/L, Hb: 8.8 g/dL). A follow-up confirmed that her condition improved gradually. AL treatment of severe malaria can cause delayed hemolytic anemia. Patients should be followed up for up to 4 weeks to detect signs of hemolysis and provide appropriate symptomatic treatment.
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Nguyen, Y.T.H., Wang, Z., Maruyama, H., Horii, Y., Nonaka, N., Yoshida, A.
Journal of Food Safety 37 ( 2 ) 2017年5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 Food Safety
© 2016 Wiley Periodicals, Inc. Ascarid larva migrans syndrome (ascarid LMS) is caused by ascarid roundworms including Ascaris suum. In East Asia, ascarid LMS has been considered as a food-borne disease in adulthood who has the dietary habitat of consuming raw or lightly cooked meat and organ meats. To evaluate the potential risk of A. suum infection from these foods, Ascaris specific real-time PCR was developed. The assay could constantly detect A. suum DNA up to 10 fg. Its specificity was confirmed by non-amplification with Toxocara canis and Toxocara cati DNA. A. suum DNA could be amplified from not only a single larva but also mouse liver spiked with a larva. Moreover, the assay could detect A. suum DNA in experimentally infected mouse liver, and showed higher sensitivity than a conventional digestion method. This real-time PCR assay would be useful for detecting the A. suum larval contamination in meat and organ meats. Practical applications: It has been considered that one of the most important risk factors for ascarid LMS in humans is the consumption of raw or undercooked meat or organ meats of domestic animals infected with Ascaris suum. Thus, we developed the novel real-time PCR with the high sensitivity and specificity in order to specifically detect A. suum DNA from animal tissues. This assay can be applied to the meat inspection procedure for the identification of parasite larval contamination that may adversely impact on public health as well as on animal health and welfare.
DOI： 10.1111/jfs.12301
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Kambe, D., Takeoka, K., Ogawa, K., Doi, K., Maruyama, H., Yoshida, A., Suenaga, T., Kageyama, T.
Multiple sclerosis and related disorders 13 116 - 118 2017年4月
記述言語：英語 掲載種別：症例報告 出版者・発行元：Multiple Sclerosis and Related Disorders
© 2017 Elsevier B.V. A 53-year-old woman was admitted to the department of neurology in Tenri Hospital because of progressive thoracic myelitis a month after she had eaten uncooked bovine liver. A previous episode of right optic neuritis and a positive test for serum anti-aquaporin-4 antibodies indicated a diagnosis of neuromyelitis optica spectrum disorders. Although the patient initially recovered with the reduction of anti-aquaporin-4 antibodies during treatment with intravenous methylprednisolone infusion and plasma exchange, her neurological symptoms deteriorated soon after the completion of plasma exchange. Western blotting analysis detected anti-Toxocara canis antibodies in the serum; thus, the patient underwent oral albendazole treatment. This resulted in the alleviation of her symptoms. We therefore consider that rigorous investigation should be encouraged to detect rare pathogens including parasites in cases of treatment-resistant neuromyelitis optica spectrum disorders.
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Toxocara canis myelitis involving the lumbosacral region: a case report. 査読あり
Hiramatsu Y, Yoshimura M, Saigo R, Arata H, Okamoto Y, Matsuura E, Maruyama H, Takashima H
The journal of spinal cord medicine 40 ( 2 ) 241 - 245 2017年3月
記述言語：英語 掲載種別：症例報告 出版者・発行元：Journal of Spinal Cord Medicine
© 2015, © The Academy of Spinal Cord Injury Professionals, Inc. 2015. Context: Toxocara canis is a parasite known to cause visceral larva migrans. The infection rarely affects the central nervous system but there have been several reports of myelitis caused by visceral larva migrans due to Toxocara canis. In previous reported cases, the lesions were located in the thoracic or cervical spinal cord. To the best of our knowledge, this is the first report of a lesion involving the lumbosacral region. Findings: A 60-year-old man developed weakness and dysesthesia in the lower limbs. The symptoms resolved spontaneously, but recurred after five months. One month later, the patient developed pollakiuria and constipation. He was a dog owner and frequently ate raw chicken meat and beef liver. Sagittal T2-weighted image (T2WI) showed swelling and hyperintensity in the spinal cord from T10 to the lumbosacral region and focal nodular enhancement on the posterior segment of the lumbar spinal cord. Blood cell counts showed slight eosinophilia and elevated serum immunoglobulin E level. Cerebrospinal fluid examination showed slight pleocytosis with eosinophilia. Enzyme-linked immunosorbent assay showed high levels of anti-Toxocara antibodies in the serum and cerebrospinal fluid. In addition, confirmatory test by Western blot was positive. The patient was initially treated with intravenous methylprednisolone with slight improvement in muscle weakness. Albendazole was added with a second course of intravenous methylprednisolone. The muscle weakness in the lower limbs improved considerably, and swelling and hyperintensity on T2WI almost disappeared. Conclusion: Our results suggest that Toxocara canis myelitis cannot be discounted even if the myelitis involves the lumbosacral region.
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Kikuchi T, Hino A, Tanaka T, Aung MP, Afrin T, Nagayasu E, Tanaka R, Higashiarakawa M, Win KK, Hirata T, Htike WW, Fujita J, Maruyama H
PLoS neglected tropical diseases 10 ( 12 ) e0005253 2016年12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：PLoS Neglected Tropical Diseases
© 2016 Kikuchi et al. The helminth Strongyloides stercoralis, which is transmitted through soil, infects 30–100 million people worldwide. S. stercoralis reproduces sexually outside the host as well as asexually within the host, which causes a life-long infection. To understand the population structure and transmission patterns of this parasite, we re-sequenced the genomes of 33 individual S. stercoralis nematodes collected in Myanmar (prevalent region) and Japan (non-prevalent region). We utilised a method combining whole genome amplification and next-generation sequencing techniques to detect 298,202 variant positions (0.6% of the genome) compared with the reference genome. Phylogenetic analyses of SNP data revealed an unambiguous geographical separation and sub-populations that correlated with the host geographical origin, particularly for the Myanmar samples. The relatively higher heterozygosity in the genomes of the Japanese samples can possibly be explained by the independent evolution of two haplotypes of diploid genomes through asexual reproduction during the auto-infection cycle, suggesting that analysing heterozygosity is useful and necessary to infer infection history and geographical prevalence.
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Optimal ELISA antigen for the diagnosis of Ascaris suum infection in humans. 査読あり
Yoshida A, Kikuchi T, Nakagaki S, Maruyama H
Parasitology research 115 ( 12 ) 4701 - 4705 2016年12月
担当区分：最終著者, 責任著者 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 Research
© 2016, Springer-Verlag Berlin Heidelberg. Ascarid nematodes, Ascaris suum, Toxocara canis and Toxocara cati, are the most important causative species of larva migrans syndrome (LMS) in humans. Although the diagnosis of ascarid LMS is generally based on serological tests, specific serological tests for A. suum infection have not been fully developed. In the present study, the sensitivity and specificity of three A. suum antigen preparations, i.e., the somatic adult worm antigen (As-SWAP), larval excretory-secretory (ES) antigens derived from infective L3 (AsiL3-ES) and larval ES from tissue migratory L3 (AsmL3-ES), were evaluated for the serodiagnosis of A. suum infection in enzyme-linked immunosorbent assay (ELISA). We found that all A. suum antigen preparations showed positive reaction to all sera from A. suum-infected mice, while only AsmL3-ES obtained 100 % detection of anti-A. suum antibodies in human visceral ascarosis patients. Comparing the reactivity of each A. suum antigen, sera from both A. suum-infected mice and human patients bound to AsiL3-ES significantly weaker than As-SWAP and AsmL3-ES. Moreover, the OD 450 values of ELISA with the A. suum antigen preparations and T. canis larval ES antigen (TciL3-ES) were compared in order to discriminate between ascarosis and toxocarosis. Linear discriminant analysis showed that diagnosis based on TciL3-ES and AsmL3-ES ELISA gave the most reliable result for the discrimination of infecting species. In conclusion, the application of AsmL3-ES antigen in ELISA can be recommended for the serodiagnosis of A. suum infection in humans.
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A novel method to assess the biodiversity of parasites using 18S rDNA Illumina sequencing; parasitome analysis method. 査読あり
Hino A, Maruyama H, Kikuchi T
Parasitology international 65 ( 5 Pt B ) 572 - 575 2016年10月
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Larva migrans syndrome caused by Toxocara and Ascaris roundworm infections in Japanese patients. 査読あり
Yoshida A, Hombu A, Wang Z, Maruyama H
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 35 ( 9 ) 1521 - 9 2016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：European Journal of Clinical Microbiology and Infectious Diseases
© 2016, The Author(s). Larva migrans syndrome (LMS) caused by Toxocara and Ascaris roundworms is generally believed to be more common in children, while a report from Japan suggests that it is more common in adults. We conducted a large-scale retrospective study to confirm these findings and to clarify what caused the difference between Japan and other countries, to reveal overlooked aspects of this disease. The clinical information of 911 cases which we diagnosed as Toxocara or Ascaris LMS during 2001 and 2015 was analysed. Information used included age, sex, address (city or county), chief complaint, present history, dietary history, overseas travelling history, medical imaging findings and laboratory data (white blood cell count, peripheral blood eosinophil number and total IgE). The sex ratio of the disease was 2.37 (male/female = 641/270). The number of patients not younger than 20 years old were 97.8 and 95.1 % among males and females, respectively. Major disease types were visceral, ocular, neural and asymptomatic. The visceral type was more prevalent in older patients, while younger patients were more vulnerable to ocular symptoms. More than two-thirds of the patients whose dietary habits were recorded had a history of ingesting raw or undercooked animal meat. LMS caused by Toxocara or Ascaris is primarily a disease of adult males in Japan, who probably acquired infections by eating raw or undercooked animal meat/liver. Healthcare specialists should draw public attention to the risk of raw or undercooked animal meat in Europe as well.
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Thoracoscopic examination of empyema in a patient with sparganosis mansoni.
Takeda K, Suzuki J, Nagai H, Watanabe K, Yokoyama A, Ando T, Suzuki J, Ohshima N, Masuda K, Tamura A, Akagawa S, Kitani M, Hebisawa A, Matsui H, Kobayashi N, Maruyama H, Ohta K
Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 22 ( 2 ) 120 - 3 2016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 Infection and Chemotherapy
© 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. A 27-year-old man was admitted to our hospital with right pleural effusion. He had suffered from right chest and back pain and a high fever for one week prior to the admission. He had been treated with clarithromycin without improvement. Since thoracoscopy under local anesthesia revealed purulent effusion, synechiae and fibrous septa in the thoracic cavity, synechiotomy was performed and we started antibiotic treatment with the diagnosis of acute bacterial empyema. At the same time, we also suspected parasitic infection because of massive eosinophilic infiltration in pleural effusion and his dietary history of eating raw frogs. During the course of the disease, he had an infiltration in the right lower lobe and pneumothorax. Finally, we diagnosed him with sparganosis mansoni because his serum as well as pleural effusion was positive for the binding to sparganosis mansoni plerocercoid antigen, without any positive findings in bacteriology. His pleural effusion and lung infiltration were resolved after the administration of a high-dose praziquantel. We report this rare parasitic empyema with findings by thoracoscopic examination.
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Palomares-Rius JE, Tsai IJ, Karim N, Akiba M, Kato T, Maruyama H, Takeuchi Y, Kikuchi T
BMC genomics 16 ( 1 ) 845 2015年10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：BMC Genomics
© 2015 Palomares-Rius et al. Background: Bursaphelenchus xylophilus is an emerging pathogenic nematode that is responsible for a devastating epi demic of pine wilt disease across Asia and Europe. In this study, we report the first genome-wide variation analysis of the nematode with an aim to obtain a full picture of its diversity. Methods: We sequenced six keyB.xylophilusstrains using Illumina HiSeq sequencer. All the strains were isolated in Japan and have been widely used in previous studies.Detection of genomic variations were done by mapping the reads to the reference genome. Results: Over 3Mb of genetic variations, accounting for 4.1% of the total genome, were detected as single nucleotide polymorphisms or small indels, suggesting multiple introductions of this invaded species from its native area into the country. The high level of genetic diversity of the pine wood nematode was related to its pathogenicity and ecological trait differences. Moreover, we identified a gene set affected by genomic variation, and functional annotation of those genes indicated that some of them had potential roles in pathogenesis. Conclusions: This study provides an important resource for understanding the population structure, pathogenicity and evolutionary ecology of the nematode, and further analysis based on this study with geographically diverse B. xylophilus populations will greatly accelerate our understanding of the complex evolutionary/epidemic history of this emerging pathogen.
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Shimizu S, Kikuchi T, Koga M, Kato Y, Matsuoka H, Maruyama H, Kimura M, Research Group on Chemotherapy of Tropical Diseases.
Travel medicine and infectious disease 13 ( 3 ) 235 - 40 2015年5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：Travel Medicine and Infectious Disease
© 2014 Elsevier Ltd. All rights reserved. Background Recently, a dose of 30 mg (base) primaquine daily for 14 days is increasingly recommended for radical cure of Plasmodium vivax malaria. However, total primaquine doses, or those per body weight, are also recognized as important. In Japan, primaquine is not a licensed medicine, but has been used through the Research Group on Chemotherapy of Tropical Diseases for > 3 decades. Methods Based on clinical records submitted to the Research Group, patients with P. vivax and Plasmodium ovale malaria treated with primaquine were analyzed to determine the efficacy and safety of the antimalarial drug. Results Seventy-five P. vivax cases, including 3 in children, and 19 P. ovale cases were enrolled. Five of the P. vivax cases demonstrated at least one relapse despite primaquine therapy. Total primaquine doses per body weight were obtained in 4 of the 5 relapsed patients, presenting 9 malaria episodes totally, and most of the primaquine failures were caused with a total dose ≥3.5 mg/kg. Liver function disturbance was reported in 2 cases. Conclus ion In order to optimize radical cure of P. vivax, the total primaquine dose per body weight should be considered, at least 3.5 mg/kg or even more if contracted in countries with significant drug resistance. Possibility of primaquine hepatotoxicity in chronic liver disease patients remains to be elucidated.
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Differential serodiagnostics of toxocara canis and toxocara cati - is it possible? 査読あり
Poulsen C., Skov S., Yoshida A., Skallerup P., Maruyama H., Thamsborg S., Nejsum P.
Parasite Immunology 37 ( 4 ) 204 - 207 2015年4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：Parasite Immunology
© 2015 John Wiley & Sons Ltd. One of the most common zoonotic helminth infections is caused by species in the genus Toxocara, particularly Toxocara canis and T. cati (Syn. T. mystax). However, their relative contribution to toxocarosis in humans remains largely unknown because causative larvae are seldom recovered and uncertainties regarding the validity of existing serological assays. In this study, we used sera from a pig model experimentally infected with T. canis and T. cati to evaluate whether a Western blot could discriminate between the two species. No proteins were observed that could be used as a diagnostic tool. In addition, a heterogenic protein pattern between individual hosts was found, which was most pronounced in the T. cati-infected pigs. There is therefore an urgent need to optimize and validate current methods or develop new species-specific serological methods in order to implement appropriate control measures.
DOI： 10.1111/pim.12181
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New zoonotic cases of Onchocerca dewittei japonica (Nematoda: Onchocercidae) in Honshu, Japan. 査読あり
Uni S, Fukuda M, Otsuka Y, Hiramatsu N, Yokobayashi K, Takahashi H, Murata S, Kusatake K, Morita E, Maruyama H, Hasegawa H, Shiwaku K, Ramli R, Azirun MS, Takaoka H
Parasites & vectors 8 59 2015年1月
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Paragonimiasis in Japan: a twelve-year retrospective case review (2001-2012). 査読あり
Nagayasu E, Yoshida A, Hombu A, Horii Y, Maruyama H
Internal medicine (Tokyo, Japan) 54 ( 2 ) 179 - 86 2015年
担当区分：最終著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Internal Medicine
© 2015 The Japanese Society of Internal Medicine. All rights reserved. Objective: Paragonimiasis, or lung fluke infection, is a food-borne parasitic disease caused by infection with trematodes belonging to the genus Paragonimus. Although paragonimiasis was once considered successfully controlled in the 1970s, new cases began to emerge in the late 1980s. To apprehend the current-day situation of the re-emergent cases of paragonimiasis in Japan, we conducted a retrospective review of 443 patients who were referred to our laboratory and diagnosed as having paragonimiasis during 2001-2012. Methods: Patients were diagnosed as having paragonimiasis based primarily on immunodiagnostic methods in addition to clinical, laboratory, and radiographic findings. Patient data were extracted from consultation sheets from attending physicians and were analyzed. Results: Majority of the patients were residents of Kyushu Island. However, a substantial number of cases were also from other parts of Japan. Immigrants (mostly from China, Thailand, and Korea) accounted for a quarter of the cases. Native Japanese contracted paragonimiasis by consuming wild boar meat or freshwater crabs, whereas immigrants contracted the infection almost exclusively by consumption of freshwater crabs. Eosinophilia and elevated serum IgE levels were found in around 80% of the patients. Parasite egg detection was documented only in 11.7% of the cases, showing the reliance on serological tests for diagnosing paragonimiasis in current clinical practice. Conclusion: Paragonimiasis remains a public health issue in Japan, and the situation should be closely monitored.
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Kodama M, Akaki M, Tanaka H, Maruyama H, Nagayasu E, Yokouchi T, Arimura Y, Kataoka H
Journal of medical case reports 8 ( 1 ) 346 2014年10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 Medical Case Reports
© 2014 Al-Kandari et al.; licensee BioMed Central Ltd. Introduction: Paragonimiasis is a food-borne infection caused by Paragonimus parasites. The lungs and pleura are the primary sites for the infection; however, ectopic infection can occur in other organs such as skin, liver and brain. It is difficult to make a diagnosis of ectopic paragonimiasis due to an ignorance of, and unfamiliarity with the disease. We report the case of a patient with subcutaneous paragonimiasis diagnosed by histopathological analysis and serological testing. Case presentation: A 39-year-old Chinese immigrant woman presented with a subcutaneous nodule in her left lower back. The nodule was initially suspected of lipoma and she was followed up on without any treatment. However, it gradually indurated and the nodule was resected surgically. A magnetic resonance imaging scan revealed a polycystic lesion with inhomogeneous low or high intensity on T1-or T2-weighted images, respectively. The rim of the lesion was enhanced after contrast enhancement, but the inside did not show high-signal intensity. A histological analysis of the surgically resected specimen revealed variable-sized tubulo-cystic structures. The cyst wall showed a granulomatous change with scant eosinophilic infiltration. A number of parasite ova were observed in the necrotic tissue inside the cysts, and a parasite body with a presumed oral sucker and reproductive organ was also detected, suggesting a trematode infection. A subsequent serological examination showed a positive reaction of her serum to the Paragonimus westermani antigen. No abnormal findings were found on her chest computed tomography scan. The diagnosis of subcutaneous paragonimiasis caused by Paragonimus westermani was made. Conclusions: We report a case presenting only as a non-migratory subcutaneous nodule without any pleuropulmonary lesion, which was initially suspected of lipoma but denied by magnetic resonance imaging scan results. The case was subsequently diagnosed as subcutaneous paragonimiasis from the results of histopathological analysis and serological testing.
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Efficient de novo assembly of highly heterozygous genomes from whole-genome shotgun short reads.
Kajitani R, Toshimoto K, Noguchi H, Toyoda A, Ogura Y, Okuno M, Yabana M, Harada M, Nagayasu E, Maruyama H, Kohara Y, Fujiyama A, Hayashi T, Itoh T
Genome research 24 ( 8 ) 1384 - 95 2014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：Genome Research
Although many de novo genome assembly projects have recently been conducted using high-throughput sequencers, assembling highly heterozygous diploid genomes is a substantial challenge due to the increased complexity of the de Bruijn graph structure predominantly used. To address the increasing demand for sequencing of nonmodel and/or wildtype samples, in most cases inbred lines or fosmid-based hierarchical sequencing methods are used to overcome such problems. However, these methods are costly and time consuming, forfeiting the advantages of massive parallel sequencing. Here, we describe a novel de novo assembler, Platanus, that can effectively manage high-throughput data from heterozygous samples. Platanus assembles DNA fragments (reads) into contigs by constructing de Bruijn graphs with automatically optimized k-mer sizes followed by the scaffolding of contigs based on paired-end information. The complicated graph structures that result from the heterozygosity are simplified during not only the contig assembly step but also the scaffolding step. We evaluated the assembly results on eukaryotic samples with various levels of heterozygosity. Compared with other assemblers, Platanus yields assembly results that have a larger scaffold NG50 length without any accompanying loss of accuracy in both simulated and real data. In addition, Platanus recorded the largest scaffold NG50 values for two of the three low-heterozygosity species used in the de novo assembly contest, Assemblathon 2. Platanus therefore provides a novel and efficient approach for the assembly of gigabase-sized highly heterozygous genomes and is an attractive alternative to the existing assemblers designed for genomes of lower heterozygosity. © 2014 Kajitani et al.
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A 71-year-old Man from Japan with Eosinophilia and a Nodular Lesion in the Lung: Paragonimiasis
Nawa Y., Maruyama H., Tomita M.
Clinical Cases in Tropical Medicine 268 - 272 2014年5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：Clinical Cases in Tropical Medicine
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Assessment of helminth biodiversity in wild rats using 18S rDNA based metagenomics. 査読あり 国際共著
Tanaka R, Hino A, Tsai IJ, Palomares-Rius JE, Yoshida A, Ogura Y, Hayashi T, Maruyama H, Kikuchi T
PloS One 9 ( 10 ) e110769 2014年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：PLoS ONE
© 2014 Tanaka et al. Parasite diversity has important implications in several research fields including ecology, evolutionary biology and epidemiology. Wide-ranging analysis has been restricted because of the difficult, highly specialised and time-consuming processes involved in parasite identification. In this study, we assessed parasite diversity in wild rats using 18S rDNA-based metagenomics. 18S rDNA PCR products were sequenced using an Illumina MiSeq sequencer and the analysis of the sequences using the QIIME software successfully classified them into several parasite groups. The comparison of the results with those obtained using standard methods including microscopic observation of helminth parasites in the rat intestines and PCR amplification/sequencing of 18S rDNA from isolated single worms suggests that this new technique is reliable and useful to investigate parasite diversity.
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Kanai S., Nakamura T., Nagato M., Taniguchi M., Nakamura I., Kawaguchi A., Shimomatsuya T., Maruhashi K., Kusui T., Maruyama H.
Japanese Journal of Gastroenterological Surgery 47 ( 5 ) 281 - 289 2014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：Japanese Journal of Gastroenterological Surgery
A 73-year-old man who consulted our hospital with a chief complaint of upper abdominal pain was admitted with a diagnosis of acute pancreatitis. An image of a localized irregular narrow segment was observed in the main pancreatic duct of the pancreatic head upon ERCP, with a poorly contrasting region measuring 8 mm in size, corresponding to the narrow segment observed on abdominal CT. A blocked main pancreatic duct and common bile duct were observed in the vicinity of the pancreaticobiliary duct upon MRCP. Based on the laboratory finding, pancreaticoduodenectomy and right nephrectomy were performed with a preoperative diagnosis of pancreatic cancer and right renal cell cancer. As no malignant findings were observed in the resected specimen, and only plant tissue was found in the main pancreatic duct in histopathological laboratory findings, it was diagnosed as obstructive pancreatitis caused by a foreign substance in the main pancreatic duct. The mechanism of the appearance of the foreign substance in the main pancreatic duct was unknown in this case because the patient had no history of drug use that was likely to influence the function of the papillary sphincter muscle or a history of choledocholithiasis, and because no evident morphological defects in the duodenal papilla were found through imaging.© 2014 The Japanese Society of Gastroenterological Surgery.
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動物由来回虫症に対するアルベンダゾールの有効性の検討
本部エミ、吉田彩子、長安英治、黒木美香、丸山治彦
Clinical Parasitology 24 ( 1 ) 91 - 93 2013年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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寄生虫症血清診断から見た肺吸虫症の最近の動向
長安英治、吉田彩子、本部エミ、黒木美香、丸山治彦
Clinical Parasitology 24 ( 1 ) 100 - 102 2013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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動物由来回虫症に対するアルベンダゾールの有効性の検討
本部エミ、吉田彩子、長安英治、黒木美香、丸山治彦
Clinical Parasitology 24 ( 1 ) 91 - 93 2013年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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寄生虫症血清診断から見た肺吸虫症の最近の動向
長安英治、吉田彩子、本部エミ、黒木美香、丸山治彦
Clinical Parasitology 24 ( 1 ) 100 - 102 2013年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Efficacy and safety of paromomycin for treating amebiasis in Japan. 査読あり
Kikuchi T, Koga M, Shimizu S, Miura T, Maruyama H, Kimura M.
Parasitology International 62 ( 6 ) 497 - 501 2013年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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The role of B-cells in immunity against adult Strongyloides venezuelensis. 査読あり
El-Malky MA, Maruyama H, Al-Harthi SA, El-Beshbishi SN, Ohta N.
Parasites & Vectors 24 ( 6 ) 148 2013年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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山川 英晃, 高柳 昇, 石黒 卓, 多田 麻美, 丸山 治彦, 杉田 裕
日本呼吸器学会誌 = Annals of the Japanese Respiratory Society 2 ( 3 ) 289 - 294 2013年5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：日本呼吸器学会
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Identification of a bacteria-like ferrochelatase in Strongyloides venezuelensis, an animal parasitic nematode. 査読あり
Nagayasu E, Ishikawa SA, Taketani S, Chakraborty G, Yoshida A, Inagaki Y, Maruyama H.
PLoS One 8 ( 3 ) e58458 2013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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ke ferrochelatase in Strongyloides venezuelensis, an animal parasitic nematode. 査読あり
Nagayasu E, Ishikawa SA, Taketani S, Chakraborty G, Yoshida A, Inagaki Y, Maruyama H
PLoS One 8 ( 3 ) 58458 - 58458 2013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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Transcriptomic analysis of four developmental stages of Strongyloides venezuelensis. 査読あり
Nagayasu E, Ogura Y, Itoh T, Yoshida A, Chakraborty G, Hayashi T, Maruyama H
Parasitology International 62 ( 1 ) 57 - 65 2013年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Transcriptomic analysis of four developmental stages of Strongyloides venezuelensis.
Nagayasu E, Ogura Y, Itoh T, Yoshida A, Chakraborty G, Hayashi T, Maruyama H
Parasitology International 62 ( 1 ) 57 - 65 2013年2月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Transcriptomic analysis of four developmental stages of Strongyloides venezuelensis.
Nagayasu E, Ogura Y, Itoh T, Yoshida A, Chakraborty G, Hayashi T, Maruyama H
Parasitology international 62 ( 1 ) 57 - 65 2013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：Parasitology International
Strongyloides venezuelensis is one of some 50 species of genus Strongyloides, obligate gastrointestinal parasites of vertebrates, responsible for strongyloidiasis in humans and other domestic/companion animals. Although S. venezuelensis has been widely used as a model species for studying human/animal strongyloidiasis, the sequence information for this species has been quite limited. To create a more comprehensive catalogue of expressed genes for identification of genes potentially involved in animal parasitism, we conducted a de novo sequencing analysis of the transcriptomes from four developmental stages of S. venezuelensis, using a Roche 454 GS FLX Titanium pyrosequencing platform. A total of 14,573 contigs were produced after de novo assemblies of over 2. million sequencing reads and formed a dataset "Vene454". BLAST homology search of Vene454 against proteome and transcriptome data from other animal-parasitic and non-animal-parasitic nematode species revealed several interesting genes, which may be potentially related to animal parasitism, including nicotinamide phosphoribosyltransferase and ferrochelatase. The Vene454 dataset analysis also enabled us to identify transcripts that are specifically enriched in each developmental stage. This work represents the first large-scale transcriptome analysis of S. venezuelensis and the first study to examine the transcriptome of the lung L3 developmental stage of any Strongyloides species. The results not only will serve as valuable resources for future functional genomics analyses to understand the molecular aspects of animal parasitism, but also will provide essential information for ongoing whole genome sequencing efforts in this species. © 2012 Elsevier Ireland Ltd.
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[Pharmacotherapy of parasitic and tropical diseases in Japan].
Maruyama H, Kimura M
Nihon rinsho. Japanese journal of clinical medicine 70 ( 12 ) 2205 - 17 2012年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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[Pharmacotherapy of parasitic and tropical diseases in Japan].
Maruyama H., Kimura M.
Nihon rinsho. Japanese journal of clinical medicine 70 ( 12 ) 2205 - 2217 2012年12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：Nihon rinsho. Japanese journal of clinical medicine
Parasitic and tropical diseases are relatively rare in Japan. However, physicians have to realize that a patient may visit your hospital today, who is infected with a potentially fatal parasite. This review focuses on the treatment of the domestic and imported parasitic infections in Japan. Many of the drugs against parasitic diseases, especially imported protozoan diseases, have not been approved, nor have been covered by the National Health Insurance Policy. Therefore, patients who need pharmacotherapy with an unapproved drug have to be treated in one of the hospitals of the Research Group on Chemotherapy of Tropical Diseases, which imports effective drugs against major tropical diseases.
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Efficacy and safety of atovaquone-proguanil in treating imported malaria in Japan: the second report from the research group. 査読あり
Kimura M, Koga M, Kikuchi T, Miura T, Maruyama H.
Parasitology International 61 ( 3 ) 466 - 469 2012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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Kimura M., Koga M., Kikuchi T., Miura T., Maruyama H.
Parasitology International 61 ( 3 ) 466 - 469 2012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
Malaria remains an important health risk among travelers to tropical/subtropical regions. However, in Japan, only 2 antimalarials are licensed for clinical use - oral quinine and mefloquine. The Research Group on Chemotherapy of Tropical Diseases introduced atovaquone-proguanil in 1999, and reported on its excellent antimalarial efficacy and safety for treating non-immune patients with uncomplicated Plasmodium falciparum malaria (20 adult and 3 pediatric cases) in 2006. In the present study, additional cases of malaria were analyzed to confirm the efficacy and safety of this antimalarial drug. Fourteen adult and 2 pediatric cases of P. falciparum malaria and 13 adult cases and 1 pediatric case of P. vivax/. ovale malaria were successfully treated with atovaquone-proguanil, including 3 P. falciparum cases in which the antecedent treatment failed. Two patients with P. vivax malaria were treated twice due to primaquine treatment failure as opposed to atovaquone-proguanil treatment failure. Except for 1 patient with P. falciparum malaria who developed a moderate liver function disturbance, no significant adverse effects were observed. Despite the intrinsic limitations of this study, which was not a formal clinical trial, the data showed that atovaquone-proguanil was an effective and well-tolerated therapeutic option; licensure of this drug in Japan could greatly contribute to individually appropriate treatment options. © 2012 Elsevier Ireland Ltd.
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A novel C-type lectin identified by EST analysis in tissue migratory larvae of Ascaris suum 査読あり
Yoshida A, Nagayasu E, Horii Y, Maruyama H.
Parasitology Research 110 ( 4 ) 1583 - 1586 2012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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A novel C-type lectin identified by EST analysis in tissue migratory larvae of Ascaris suum. 査読あり
Yoshida A, Nagayasu E, Horii Y, Maruyama H
Parasitology Research 110 ( 4 ) 1583 - 1586 2012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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術前に肝内胆管癌と診断され，抗体検査から肝蛭症が疑われた1切除例 査読あり
黒川 友博, 植田 貴徳, 榎本 剛史, 山本 雅由, 丸山 治彦, 大河内 信弘
日本消化器外科学会雑誌 45 ( 4 ) 387 - 393 2012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：The Japanese Society of Gastroenterological Surgery
症例は51歳の男性で，全身に掻痒を伴う膨疹を主訴に受診した．血液検査でトランスアミナーゼ上昇を認めたため精査したところ，腹部超音波で肝S7，8に3cm大の腫瘤性病変を認めた．CTでは同部に早期から造影されるが内部の造影効果の弱い辺縁高吸収，内部低吸収な結節を指摘された．他に原発巣を認めず，各種腫瘍マーカー・感染症マーカー陰性であったが，CT造影パターンより肝内胆管癌と診断し，肝部分切除術を施行した．病理組織学的診断では，悪性所見は認められず，壊死を伴う肉芽腫性病変であった．異物巨細胞が目立ち，高度な好酸球浸潤により形成されるCharcot-Leyden結晶が認められたことから寄生虫の可能性が考えられたが，虫体，虫卵は指摘できなかった．血清抗体検査で，肝蛭の抗体が高値ではなかったが，ほかの抗体と比べると完全に陰性と判断できるほど低くなく末梢好酸球が高値ではないことから過去に感染した肝蛭症が強く疑われた．
DOI： 10.5833/jjgs.45.387
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A patient who developed toe necrosis due to poor blood circulation after an interdigital tick bite 査読あり
Yamazaki H, Yamaguchi K, Iwase T, Niki T, Kusunose K, Tomita N, Taketani Y, Yamada H, Soeki T, Wakatsuki T, Fukunaga Y, Nakanishi H, Maruyama H, Matsuoka H, Sata M
Journal of Cardiology Cases 4 ( 2 ) e106 - e109 2011年10月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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A patient who developed toe necrosis due to poor blood circulation after an interdigital tick bite
Yamazaki H, Yamaguchi K, Iwase T, Niki T, Kusunose K, Tomita N, Taketani Y, Yamada H, Soeki T, Wakatsuki T, Fukunaga Y, Nakanishi H, Maruyama H, Matsuoka H, Sata M
Journal of Cardiology Cases 4 ( 2 ) e106 - e109 2011年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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A patient who developed toe necrosis due to poor blood circulation after an interdigital tick bite. 査読あり
Yamazaki H, Yamaguchi K, Iwase T, Niki T, Kusunose K, Tomita N, Taketani Y, Yamada H, Soeki T, Wakatsuki T, Fukunaga Y, Nakanishi H, Maruyama H, Matsuoka H, Sata M
Journal of cardiology cases 4 ( 2 ) e106 - e109 2011年10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 Cardiology Cases
A 71-year-old female had worked on a farm in the mountains and noticed itching of the left 3rd toe. She visited a local hospital due to a color change to purple in this area. Attachment of a tick was observed between the left 2nd and 3rd toes, and it was extracted. However, due to persistent pain, she was referred to our department of cardiovascular medicine for close examination and treatment. Lower extremity angiography showed that vascular visualization was poor in the area supplied by the arteries distal to the tick bite site, but the other blood vessels of the toe were clearly visualized. Toe amputation was performed and pathological examination of a surgical specimen revealed that most blood vessels near the necrosis were occluded by thrombi. We speculated that tick bite reactions were associated with thrombogenic vasculopathy. This report shows a patient who developed toe necrosis due to poor blood circulation after an interdigital tick bite. © 2011 Japanese College of Cardiology.
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Izumikawa K., Kohno Y., Izumikawa K., Hara K., Hayashi H., Maruyama H., Kohno S.
Japanese Journal of Infectious Diseases 64 ( 5 ) 428 - 432 2011年9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：Japanese Journal of Infectious Diseases
SUMMARY: We report the case of a 62-year-old man who developed eosinophilic pneumonia due to visceral larva migrans (VLM) that was possibly caused by Ascaris suum. The patient, a resident of the middle Kyushu area who was fond of eating raw porcine liver, complained of dry cough without dyspnea. The chest radiography showed a migration of infiltrative shadow. Transbronchial lung biopsy of the right middle lobe revealed massive infiltration of eosinophils. The multi-dot enzyme-linked immunosorbent assay (ELISA) and microtiter plate ELISA showed positive results for A. suum; therefore, the patient was diagnosed with VLM caused by A. suum. The patient was administered albendazole (600 mg/day) for 28 days; he recovered successfully with no adverse effects except mild liver dysfunction. Several cases of VLM caused by A. suum have been reported in Japan, with a majority of the cases being reported in Kyushu. Careful history taking of the patient's area of residence and dietary habit is essential for the diagnosis of this parasitic disease with underestimated prevalence.
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Eosinophilic pneumonia due to visceral larva migrans possibly caused by Ascaris suum: a case report and review of recent literatures 査読あり
Izumikawa K, Kohno Y, Izumikawa K, Hara K, Hayashi H, Maruyama H, Kohno S
Japanese Journal of Infectious Diseases 64 ( 5 ) 428 - 432 2011年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Kawano S., Kato J., Kawano N., Yoshimura Y., Masuyama H., Fukunaga T., Sato Y., Maruyama H., Mihara K., Ueda A., Toyoda K., Imamura T., Kitamura K.
Internal Medicine 50 ( 9 ) 975 - 981 2011年5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：Internal Medicine
Background Eosinophilic myocarditis is a rare clinical entity characterized by eosinophilia and myocardial inflammation with infiltrating eosinophils. The prognosis of patients with eosinophilic myocarditis is difficult to determine due the disease's rarity and varied causes; consequently, standard treatment has not been established. Objective To elucidate the clinical characteristics and treatment outcome of eosinophilic myocarditis, we retrospectively studied 7 patients fulfilling the criteria of the Japanese Circulation Society for eosinophilic myocarditis from among 64 patients admitted to our institution with eosinophilia over a 27-year period. Results The patients' ages at diagnosis ranged from 36 to 83 years (median: 52 years). The etiologies of the eosinophilic myocarditis were found to be idiopathic (3 patients), Churg-Strauss syndrome (2 patients), parasitic infection (1 patient) and chronic eosinophilic leukemia (CEL) (1 patient). In addition to treatment for the underlying disease, we also administered prednisolone at a dose appropriate to the disease severity (6 of 7 patients). The patient who was diagnosed with a parasitic infection was treated only with albendazole, because eosinophilic myocarditis was mild. The patient with CEL was positive for the FIP1 L1-PDGFRα fusion gene and was treated with imatinib. Eosinophilic cationic protein was a useful marker for assessing disease activity and treatment efficacy. At the end of the study, of the seven patients treated, six were alive (86%), giving a mean survival time of 37 ± 40 months (mean ± SD). Conclusion Because eosinophilic myocarditis has various etiologies, it is essential to identify the etiology of the underlying disease. In the majority of eosinophilic myocarditis patients, administration of prednisolone may be an effective therapeutic modality producing a good outcome. © 2011 The Japanese Society of Internal Medicine.
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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：日本語 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：研究論文（学術雑誌） 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：日本語 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：日本語 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：日本語 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
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：日本語 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.
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Research on calpain of Schistosoma japonicum as a vaccine candidate
Ohta N., Kumagai T., Maruyama H., Yoshida A., He Y., Zhang R.
Parasitology International 53 ( 2 ) 175 - 181 2004年6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
Vaccine development by the use of calpain of Schistosoma japonicum has been tried in our laboratory. We cloned cDNA encoding the heavy chain of S. japonicum calpain, and prepared recombinant molecule of a possible vaccine region of the heavy chain. When BALB/c mice were immunized with our recombinant calpain of S. japonicum with Freund's complete adjuvant, we observed significant reduction in worm burden (41.2% reduction, P<0.05), and also significant anti-fecundity effects. In this sense, calpain of S. japonicum seems to have infection control as well as anti-disease effects. Mechanisms of vaccine effects of calpain remain to be clarified, however, several effecter mechanisms are suspected. In immunized mice, raised level of iNos expression was observed, while adhesion of peritoneal exudates cells were also observed in the presence of calpain-immunized sera, suggesting the possibilities of both cellular and humoral protective mechanisms. We examined tissue distribution of calpain in various developmental stages of S. japonicum. Strong signal was observed around excretory grand of cercariae, and they secreted calpain during their migratory movement tested in vitro. Together with the findings, calpain seems to induce larvicidal effects in the immunized mice. We observed time-course kinetics of antibody production against vaccine candidates in experimental S. japonicum infection in pigs. Although significant levels of antibody production were observed for paramyosin and GST, no significant antibody production was observed for calpain. This suggests that calpain is less immunogenic, and route of immunization and/or choice of adjuvant are important in future trials of calpain vaccine. © 2004 Elsevier Ireland Ltd. All rights reserved.
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Induction of cellular immunity by anti-idiotypic antibodies mimicking GD2 ganglioside
Basak S., Birebent B., Purev E., Somasundaram R., Maruyama H., Zaloudik J., Swoboda R., Strittmatter W., Li W., Luckenbach A., Song H., Li J., Sproesser K., Guerry D., Nair S., Furukawa K., Herlyn D.
Cancer Immunology, Immunotherapy 52 ( 3 ) 145 - 154 2003年4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：Cancer Immunology, Immunotherapy
Gangliosides are potentially useful targets for tumor destruction by antibodies. However, the role of gangliosides in T cell-mediated immunity to tumors is unclear. We produced three murine monoclonal anti-idiotypic antibodies (Ab2) against a monoclonal antibody (Ab1) that binds strongly to melanoma-associated GD2 ganglioside and weakly to GD3 ganglioside. All three Ab2 induced anti-anti-idiotypic antibodies (Ab3) with Ab1-like binding specificity to tumor cells and antigen in rabbits. The Ab3 specifically bound to GD2 + tumor cells and isolated GD2, and shared idiotopes with the Ab1. Two of the three Ab2 induced GD2-specific delayed-type hypersensitivity responses in BALB/c and C57BL/6 mice, but not in C57BL/6/CD4 -/- mice. Peripheral blood mononuclear cells (PBMC) from a melanoma patient proliferated specifically in response to in vitro stimulation with Ab2. Proliferation was accompanied by Th1-type cytokine production. Our studies demonstrate the induction of ganglioside-specific T cell-dependent immunity by Ab2 in mice. These T cells showed specific reactivity to ganglioside expressed by tumor cells.
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Maruyama H., Aoki M., Okamura S., Yoshida A., Itagaki T., Ohta N.
Parasitology International 52 ( 1 ) 35 - 39 2003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：Parasitology International
In order to study the mucosal invasion of a rodent intestinal nematode in bird intestine, chicks were infected with the intestinal nematode of rodents, Strongyloides venezuelensis, by subcutaneous larva inoculation and adult worm implantation. No evidence was obtained for larvae reaching the lungs or the intestine after infective larva inoculation. Adult worms implanted in the small intestine invaded the mucosa and remained there at least for 24 h, whereas those implanted in the caecum were trapped by mucus, and did not invade the mucosa. Mucosal invasion of adult worms in the small intestine was confirmed by histological examination. The number of adult worms in the intestinal mucosal tissue dropped rapidly within the first 24 h, which was associated with infiltrating granulocytes around the worms. The present study suggests that S. venezuelensis adult worms are able to invade the intestinal tissue of chicks, which do not belong to the vertebrate class of its normal definitive host, but that they are eliminated rapidly by mucosal defense system of the bird. © 2002 Elsevier Science Ireland Ltd. All rights reserved.
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El-Malky M., Maruyama H., Hirabayashi Y., Shimada S., Yoshida A., Amano T., Tominaga A., Takatsu K., Ohta N.
Parasitology International 52 ( 1 ) 71 - 79 2003年3月
担当区分：責任著者 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
Eosinophils were examined for the capacity of attacking Strongyloides venezuelensis adult worms in the intestinal mucosa by using interleukin (IL)-5 transgenic mice. In IL-5 transgenic mice, most of the subcutaneously inoculated infective larvae were killed during migration, and only a few worms could reach the small intestine. When the same number of adult worms were surgically implanted in the small intestine of IL-5 transgenic and control mice, fecal egg output as well as the number of adult worms recovered from the intestine was significantly lower in IL-5 transgenic mice. In the intestinal mucosa of IL-5 transgenic mice, large number of eosinophils was present in the lamina propria even before adult worm implantation. The number of eosinophils increased significantly as early as 24 h after implantation and tripled by day 3, whereas mucosal eosinophilia remained low in wild-type mice. Most notably, eosinophils infiltrated into the intestinal epithelium and surrounded adult worms in IL-5 transgenic mice, which was never seen in wild-type control mice. However, IL-5 transgenic mice required the same period as normal mice to completely expel implanted adult worms. The amount of specific IgA as well as total IgA in the stool was high in IL-5 transgenic mice before adult worm implantation, and dropped rapidly after adult worm implantation. The present study suggests that eosinophils are capable of attacking adult nematodes in the intestinal epithelia, probably in conjunction with secretory IgA, although they are not enough for the complete worm expulsion. © 2002 Elsevier Science Ireland Ltd. All rights reserved.
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Maruyama H., El-Malky M., Kumagai T., Ohta N.
Parasitology 126 ( 2 ) 165 - 171 2003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：Parasitology
The parasitic female of Strongyloides venezuelensis keeps invading the epithelial layer of the host intestinal mucosa. Upon invasion, it adheres to the surface of the intestinal epithelial cells with adhesion molecules secreted from the mouth. It has been demonstrated that S. venezuelensis are expelled from the intestine because mucosal mast cells inhibit the attachment of adult worms to the mucosal surface. In the present study, we generated specific antibodies against secreted adhesion molecules to investigate their function in vivo, because these molecules have been demonstrated only in vitro in spite of the importance in the infection processes. A mouse monoclonal antibody specific to S. venezuelensis adhesion molecules inhibited the attachment of adult worms to plastic dishes and the binding of adhesion molecules to rat intestinal epithelial cells. Immunohistochemical study revealed that adhesion molecules were produced by oesophageal glands and were continuously secreted in vivo to line the wall of the tunnels formed by adult worms in the intestinal mucosa. Our findings indicate that adhesion molecules play essential roles in the infection processes of S. venezuelensis in the host intestine.
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Yoshida A., Maruyama H., Kumagai T., Amano T., Kobayashi F., Wang J., Kuribayashi K., Ohta N.
Parasitology International 51 ( 2 ) 177 - 186 2002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：Parasitology International
Effects of Schistosoma mansoni infection on anti-tumor immunity were examined in CBF1 mice with ultraviolet-induced UV♀1 fibrosarcoma cells. Although many laboratory established tumor cells had rejection mechanisms independent of CD4+ T cells, we confirmed that CD4+ cells had significant roles in rejection of UV♀1 cells in the syngeneic CBF1 mice. When we prepared two CBF1 mouse groups, S. mansoni-infected and schistosome-free, the former group showed up-regulation of Th2-like response to UV♀1 cells, whereas the latter group mice showed rather type 1-dominant patterns. Cytotoxic activity against UV♀1 cells tested in vitro, which was attributed to CD8+ cells, was significantly weaker in S. mansoni-infected mice compared with infection-free mice. In tumor challenge experiments in vivo, we observed that rapid and complete rejection of UV♀1 cells required the presence of CD8+ T cells. Under only CD4-depleted situation, survival of tumor cells in schistosome-free mice was prolonged up to 1 month or more. Under the presence of both CD4+ and CD8+ cells, S. mansoni infected mice rejected the challenged UV♀1 cells as was seen in normal mice. However, when CD8+ cells were depleted from S. mansoni-infected mice, inoculated UV♀1 cells grew more rapidly than in infection-free mice. Our results suggest that functionally polarized cytokine patterns in schistosome-infected hosts promote rapid tumor growth. © 2002 Elsevier Science Ireland Ltd. All rights reserved.
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Immunization procedures for anti-idiotypic antibody induction in mice and rats 査読あり 国際共著
Maruyama H., Sperlagh M., Zaloudik J., Liang S., Mizuki K., Molthoff C., Herlyn D.
Journal of Immunological Methods 264 ( 1-2 ) 121 - 133 2002年6月
担当区分：筆頭著者 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 Immunological Methods
Anti-idiotypic antibodies (Ab2) mimicking antigens (Ags)-defined by antibodies (Ab1) directed to tumors or pathogens have elicited Ag-specific humoral, cellular and/or protective immunity in experimental animals and in humans. In immunizations of rodents with Ab1, factors such as animal species, form of Ab1 and choice of adjuvant are crucial for the successful induction of Ab2 as candidate vaccines against tumors and pathogens. Here we survey the outcome of 362 fusion events (each event representing one animal), using nine immunization schedules in mice and seven schedules in rats and including 10 different Ab1 directed against human tumor- and immunodeficiency virus (HIV-1)-associated Ags. Ab1 IgG or F(ab′)2 were administered uncoupled or coupled to keyhole limpet hemocyanin (KLH). As adjuvants, complete and incomplete Freund's adjuvant (CFA/IFA), lipid A, aluminum hydroxide, TiterMax or vaccinia virus were used. In syngeneic immunizations with murine Ab1 in mice, F(ab′)2 coupled to KLH and emulsified in CFA/IFA preferentially induced Ab2 mimicking tumor or HIV-1 associated epitopes. In xenogeneic immunizations with mouse Ab1 in rats, various forms of Ab1 and adjuvants successfully induced Ab2 mimicking tumor Ags. © 2002 Elsevier Science B.V. All rights reserved.
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Maruyama H., Hirabayashi Y., El-Malky M., Okamura S., Aoki M., Itagaki T., Nakamura-Uchiyama F., Nawa Y., Shimada S., Ohta N.
Experimental Parasitology 100 ( 3 ) 179 - 185 2002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：Experimental Parasitology
Mechanisms for the longitudinal distribution of parasitic females of Strongyloides venezuelensis in the host intestine were investigated in mice. Adult worms were mostly recovered from the anterior-most one-third of the small intestine throughout the infection after infective larvae inoculation. Surgically implanted adult worms established well in the small intestinal mucosa, either in the duodenum or in the ileum, whereas a few worms could establish in the large intestine. Implanted worms in the small intestine remained where they were implanted until expelled. Mucosal mast cells were induced in the whole small intestine after the worm implantation. In the large intestine, a considerable number of adult worms settled in the mucosa of mutant mice, whose goblet cell mucins were undersulfated because of a mutation in sulfate-activating enzymes. In these mice, the degree of sulfation of goblet cell mucins in the large intestine was significantly reduced to the level of normal small intestine goblet cell mucins. Our results suggest that sulfated glycoconjugates, either from mucosal mast cells or goblet cells, have important effects on the longitudinal distribution of parasitic females of S. venezuelensis. Index Descriptors and Abbreviations: Strongyloides venezuelensis; Nematode; Tissue specificity; Goblet cell; Mucin; Mast cell; Sulfated carbohydrate; PBS, phosphate buffered saline. © 2002 Elsevier Science (USA). All rights reserved.
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Cholesteryl ester transfer protein deficiency causes slow egg embryonation of schistosoma japonicum
Okumura-Noji K., Sasai K., Zhan R., Kawaguchi H., Maruyama H., Tada T., Takahashi H., Okazaki M., Miida T., Sakuma N., Kimura G., Ohta N., Yokoyama S.
Biochemical and Biophysical Research Communications 286 ( 2 ) 305 - 310 2001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：Biochemical and Biophysical Research Communications
In our attempt to discover a potential cause for accumulation of cholesteryl ester transfer protein (CETP) deficiency in Eastern Asia, we studied the association of CETP deficiency with pathogenesis of Schistosoma japonicum, a life-threatening parasite peculiar to this region. The eggs of S. japonicum showed slow embryonation when cultured in CETP-deficient human plasma. Restoration of CETP to the deficient plasma rescued it, while inhibition of CETP in normal plasma did not cause slow embryonation of the cultured eggs. The egg embryonation was also retarded in the liver but not in the intestine of wild-type mice in comparison to the CETP-transgenic mice. The granulomatous lesion around the parasite eggs in the liver was less in the wild-type than in the CETP-transgenic mice. Thus, CETP deficiency may act against Schistosomiasis japonica by retarding egg embryonation, a potential cause of liver granulomatosis. It does not seem directly due to the lack of CETP activity in plasma but to abnormal lipoprotein generated by chronic CETP deficiency. © 2001 Academic Press.
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Maruyama H., Osada Y., Yoshida A., Futakuchi M., Kawaguchi H., Zhang R., Fu J., Shirai T., Kojima S., Ohta N.
Parasite Immunology 22 ( 6 ) 279 - 286 2000年6月
担当区分：筆頭著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Parasite Immunology
Mice infected with Schistosoma japonicum were resistant to the intestinal nematode, Strongyloides venezuelensis. The numbers of adult S. venezuelensis recovered from mice were significantly decreased when infections were given from 6 weeks after S. japonicum infection. Larval recovery from the lungs showed that significant numbers of subcutaneously inoculated S. venezuelensis larvae were eliminated by 3 days in S. japonicum-infected mice (P < 0.001), while histology revealed that this was associated with massive eosinophilic infiltration in the lungs. In addition, adult S. venezuelensis worms implanted in the duodenum of S. japonicum-infected mice could not establish in the intestine. This failure was associated with mucosal mastocytosis. Activation of eosinophils and intestinal mast cells was correlated with elevated expression of mRNA for interleukin (IL)-3, IL-4, and IL-5 in S. japonicum-infected mice. Sera from S. japonicum-infected mice recognized S. venezuelensis larva antigens as strongly as those from S. venezuelensis-infected mice, although transfer of sera from S. japonicum-infected mice to normal recipient mice did not protect them from S. venezuelensis challenge infection. It was concluded that the mechanisms for larval killing and adult worm expulsion of S. venezuelensis in S. japonicum-infected mice were identical to those seen in infections with S. venezuelensis only.
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Maruyama H., Yabu Y., Yoshida A., Nawa Y., Ohta N.
Journal of Immunology 164 ( 7 ) 3749 - 3754 2000年4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
We examined effects of mast cell glycosaminoglycans on the establishment of the intestinal nematode, Strongyloides venezuelensis, in the mouse small intestine. When intestinal mastocytosis occurred, surgically implanted adult worms could not invade and establish in the intestinal mucosa. In mast cell- deficient W/W(v) mice, inhibition of adult worm invasion was not evident as compared with littermate +/+ control mice. Mucosal mastocytosis and inhibition of S. venezuelensis adult worm mucosal invasion was tightly correlated. To determine effector molecules for the invasion inhibition, adult worms were implanted with various sulfated carbohydrates including mast cell glycosaminoglycans. Among sulfated carbohydrates tested, chondroitin sulfate (ChS)-A, ChS-E, heparin, and dextran sulfate inhibited invasion of adult worms into intestinal mucosa in vivo. No significant inhibition was observed with ChS-C, desulfated chondroitin, and dextran. ChS-E, heparin, and dextran sulfate inhibited adhesion of S. venezuelensis adult worms to plastic surfaces in vitro. Furthermore, binding of intestinal epithelial cells to adhesion substances of S. venezuelensis, which have been implicated in mucosal invasion, was inhibited by ChS-E, heparin, and dextran sulfate. Because adult worms of S. venezuelensis were actively moving in the intestinal mucosa, probably exiting and reentering during infection, the possible expulsion mechanism for S. venezuelensis is inhibition by mast cell glycosaminoglycans of attachment and subsequent invasion of adult worms into intestinal epithelium.
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Zhang R., Suzuki T., Takahashi S., Yoshida A., Kawaguchi H., Maruyama H., Yabu Y., Fu J., Shirai T., Ohta N.
Parasitology International 48 ( 3 ) 233 - 242 2000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
cDNA coding for calpain of Schistosoma japonicum were cloned and sequenced, and serological basis of host responses to calpain were analyzed. cDNA of calpain from S. japonicum of two different isolates, Yamanashi strain (Sj-J) and Hunan strain (Sj-C), were 2, 468 bp and 2, 465 bp in length, including the same number (2, 274) of open reading frame. Nucleotide sequence and amino acid sequence between the two calpains are 99.1% and 98.8% identity, respectively. Sj-J and Sj-C calpains were considered to be translated as a preproenzyme, and a 746-amino acid mature enzyme contains eight motifs without a signal peptide at the N-terminal based on the deduced amino acid sequences. mRNA for calpain were detectable in different developmental stages, however, sera obtained from mice immunized with recombinant calpain showed enhanced binding to cercarial antigen. Human sera from S. japonicum-infected individuals recognized the large subunit of schistosomal calpain, and light-infected sera showed stronger reactivities to the recombinant calpain than moderate/high infection cases. When we tested synthetic peptides, there were four common human B cell epitopes in schistosomal calpain, all of which are shared with S. mansoni. Together with these results, calpain of S. japonicum seems to be not only a vaccine candidate, but also a target antigen for immunodiagnosis of human schistosomiasis. Copyright (C) 2000 Elsevier Science Ireland Ltd.
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Cancer vaccines: Single-epitope anti-idiotype vaccine versus multiple- epitope antigen vaccine 査読あり
Maruyama H., Zaloudik J., Li W., Sperlagh M., Koido T., Somasundaram R., Scheck S., Prewett M., Herlyn D.
Cancer Immunology Immunotherapy 49 ( 3 ) 123 - 132 2000年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cancer Immunology Immunotherapy
In this study, we compared the immunogenicity and tumor-protective activity of anti-idiotypic antibodies mimicking a single tumor-associated epitope and tumor-associated antigen expressing multiple potentially immunogenic epitopes. We focused our study on the colorectal-carcinoma(CRC)- associated antigen GA733 (also known as CO17-1A/KS1-4/KSA/EpCAM). Monoclonal anti-idiotypic antibody (Ab2) BR3E4 was produced against murine anti-CRC mAb CO17-1A (Ab1) in rats. Full-length native GA733 protein was isolated from human tumor cells, and the extracellular domain protein (GA733-2E) was isolated from supernatants of recombinant baculovirus-infected insect cells by immunoafffinity chromatography. The immunomodulatory activity of the Ab2 was compared with that of the antigen, both in rabbits and in mice. Mice, like humans but not rabbits, express a GA733 antigen homologue on some of their normal tissues. Thus, these in vivo models allow the comparison of the immunogenicity of Ab2 and antigen in the presence (mice) and absence (rabbits) of normal tissue expression and immunological tolerance of the GA733 antigen homologue. In rabbits, aluminum-hydroxide(alum)-precipitated native GA733 antigen was superior to alum-precipitated Ab2 in inducing specific humoral immunity. In mice, alum-precipitated recombinant GA733-2E antigen, but not alum-precipitated Ab2, induced specific humoral immunity. However, when the Ab2 was administered to mice in Freund's complete adjuvant, specific humoral immune responses were elicited. Ab2 in complete Freund's adjuvant and GA733-2E in alum were compared for their capacity to induce antigen-specific cellular immunity in mice. Whereas lymphoproliferative responses were obtained with the recombinant antigen only, delayed-type hypersensitivity responses were obtained with both recombinant antigen and Ab2, although these responses were lower than after antigen immunization. The recombinant antigen in alum did not protect mice against challenge with antigen-positive syngeneic murine CRC cells. Similar studies with Ab2 BR3E4 mimicking the CO17-1A epitope were not possible because the tumor cells do not express this epitope after transfection with the human GA733-2 cDNA. However, similar studies with Ab2 mimicking the epitope defined by mAb GA733, which is expressed by the transfected tumor cells, indicated a lack of tumor- protective activity of this Ab2. In contrast, the full-length antigen expressed by recombinant adenovirus inhibited the growth of established tumors in mice. In conclusion, soluble antigen is a more potent modulator of humoral and cellular immune responses than Ab2, both administered in adjuvant. However, for induction of protective immunity, the immunogenicity of the antigen must be further enhanced, e.g., by expression of the antigen in a viral vector.
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Maruyama H., Hatano H., Kumagai T., El-Malky M., Yoshida A., Ohta N.
Experimental Parasitology 95 ( 3 ) 170 - 175 2000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：Experimental Parasitology
Immunologically damaged Strongyloides venezuelensis adult worms were examined for their mucosal invasion ability and secretion of heparin-binding adhesion substances. S. venezuelensis was expelled from male Wistar rats 4 to 5 weeks after infection. Four-week-old adult worms were smaller and had fewer eggs than 1-week-old adult worms. One-week-old, 4-week-old, and 5-week-old adult worms equally established in the recipient mouse intestine when surgically implanted. Adult worms of 4 and 5 weeks of age secreted adhesion substances as much as 1-week-old adult worms. There was no difference in the heparin-binding activities and the lectin-binding profile of adhesion substances among adult worms of different ages. The rate of secretion of adhesion substances from the mouth was also identical. Heparin-binding activities were detected in crude adult worm proteins; however, proteins of 5-week-old adult worms had weaker heparin-binding activities than those of 1-week-old adult worms. Western blotting revealed that a number of heparin-binding proteins were lost in 5-week-old adult worms. A heparin-binding protein of 42.0 kDa, which was consistently expressed in adult worms, was a possible component of heparin-binding adhesion substances which are secreted from the mouth. (C) 2000 Academic Press.
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Yoshida A., Maruyama H., Kumagai T., Amano T., Kobayashi F., Zhang M., Himeno K., Ohta N.
International Immunology 12 ( 8 ) 1117 - 1125 2000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：International Immunology
Susceptibility to Plasmodium chabaudi depends on the relative dominance of T(h)1/T(h)2 responses in host mice. A T(h)2-dominant response during the early phase of infection in susceptible A/J mice causes a fatal disease course due to severe malaria. Schistosoma mansoni is a potent inducer of a T(h)2-dominant response not only to the parasite antigens, but also to other antigens concurrently existing in the host animals. In spite of S. mansoni infection, these A/J mice escape death from malaria and showed accompanied enhanced production of IFN-γ to malaria antigens. Treatment with anti-IFN-γ mAb in S. mansoni-infected A/J mice abolished the resistance to malaria, indicating that IFN-γ was responsible for the resistance to P. chabaudi in S. mansoni-infected A/J mice. Results in this study show that under certain circumstances, S. mansoni infection can promote type 1 immune responses in A/J mice that normally develop T(h)2 responses.
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Ide H., Itoh H., Yoshida E., Kobayashi T., Tomita M., Maruyama H., Osada Y., Nakahata T., Nawa Y.
Cell and Tissue Research 297 ( 1 ) 149 - 154 1999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：Cell and Tissue Research
We recently reported that the rat mast cell proteinase inhibitor trypstatin is genetically identical with the second half of inter-α-trypsin inhibitor light chain (ITI-LC), also known as bikunin or urinary trypsin inhibitor (UTI). In this study, therefore, immunoreactivities of mast cells of various human tissues were examined with three antibodies, anti-human ITI-LC, anti-ITI, which recognizes mainly heavy chains or the sugar moiety of ITI, and anti-α 1-microglobulin (α1mG). ITI-LC immunoreactivity was strongly found in mast cells in the connective tissues of various organs except for those of the propria mucosae of small intestine. Neither anti-ITI antibody nor anti-α1mG antibody reacted with mast cells in various tissues. By reverse transcription-polymerase chain reaction (RT-PCR) analysis, α1mG/ITI-LC mRNA was not detected in the skin and tongue, and only weakly in small intestine, although ITI-LC immunoreactivity was strongly detected in these tissues. Furthermore, the mRNA was not expressed in cultured human mast cells. These results suggest that ITI-LC protein is stored in the granules of human connective tissue mast cells, though is not produced by them.
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Yoshida A., Maruyama H., Yabu Y., Amano T., Kobayakawa T., Ohta N.
Parasitology International 48 ( 1 ) 73 - 79 1999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：Parasitology International
Schistosoma mansoni infection induces T helper (Th) 2-dominant immune response in mice not only to S. mansoni itself but also to other coexisting antigens. In the present study, we challenged S. mansoni-infected mice with the intestinal nematode, Strongyloides venezuelensis, and the intracellular protozoa, Leishmania major to see whether such Th2-dominant immune responses alter susceptibility of the host to other concomitant parasitic infections. The recovery of S. venezuelensis adult worms from the small intestine was significantly decreased by S. mansoni infection, and the protection to S. venezuelensis appeared to act on migrating larvae. Antibodies elicited by S. mansoni infection showed cross-binding to third-stage larvae antigen of S. venezuelensis. On the other hand, S. mansoni infection did not affect the outcome of L. major infection in both susceptible BALB/c and resistant C57BL/6 mice. Popliteal lymph node cells of BALB/c mice expressed mRNA for interleukin (IL)-10 rather than IL-4, regardless of S. mansoni infection, and those of C57BL/6 mice expressed IFN-γ mRNA upon L. major antigen stimulation, even in S. mansoni-infected mice. Our findings suggest that Th2- dominant immune response induced by S. mansoni protects mice from intestinal helminthic infections, whereas they do not always modulate protozoal infections.
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p53 gene mutations in rectal cancer associated with schistosomiasis japonica in Chinese patients
Zhang R., Takahashi S., Orita S., Yoshida A., Maruyama H., Shirai T., Ohta N.
Cancer Letters 131 ( 2 ) 215 - 221 1998年9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：Cancer Letters
Mutations in p53 tumor suppressor gene were examined in 44 Chinese patients with rectal cancer, including 22 cases with advanced schistosomiasis japonica and 22 cases without schistosomiasis. In schistosomal rectal cancer (SRC), 13 mutations were found in 10 cases, which included 11 base-pair substitutions and two deletions. Of 11 base substitutions, nine were transitions and two were transversions and seven of them were located at CpG dinucleotides. In non-schistosomal rectal cancer (NSRC), 13 mutations were found in nine cases, all of which were base-pair substitutions. Of 13 substitutions, 10 were transitions and three were transversions and three of them were located at CpG dinucleotides. The proportion of base-pair substitutions at CpG dinucleotides was higher in SRC patients than in NSRC patients, although this was not statistically significant (P=0.054). Point mutation was frequent at codon 248 in SRC. A higher frequency of arginine missense mutations was observed in SRC than in NSRC. These observations suggest that the mutations in SRC are the result of genotoxic agents produced endogenously through the course of schistosomiasis japonica. Copyright (C) 1998 Elsevier Science Ireland Ltd.
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Maruyama H., Nawa Y., Ohta N.
Experimental Parasitology 89 ( 1 ) 16 - 20 1998年5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：Experimental Parasitology
Adhesion substances produced by adult worms of Strongyloides venezuelensis bound strongly to hepin-Sepharose beads after incubation at 37°C for 1 h. This binding was completely inhibited by highly sulfated carbohydrates such as soluble heparin, dextran surfate, fucoidan, and pentosan polysulfate. Chondroitin sulfate E and chondroitin sulfate A inhibited to a lesser degree and chondroitin sulfate C and dextran did not inhibit significantly. Carbohydrate moieties as well as the number and position of negatively charged sulfate groups of sulfated glycans were important determinants for the interaction between sulfated carbohydrates and adhesion substances. Adhesion substances of S. venezuelensis adult worms also bound to negatively charged rat red blood cells. The binding was significantly inhibited by heparin but not by mono- or disaccharides. Thus the intraction between red cells and adhesion substances was electrostatic in nature, but did not involve lectin-sugar interactions.
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Maruyama H., Nawa Y., Noda S., Mimori T.
Southeast Asian Journal of Tropical Medicine and Public Health 28 SUPPL. 1 194 - 196 1997年12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：Southeast Asian Journal of Tropical Medicine and Public Health
Ascariasis has been a representative soil-transmitted intestinal parasitic disease in warm climates. In Japan, this disease was a major and serious public health problem only a few decades ago. However, the incidence of the disease nowadays is reportedly less than 0.01%. Recently in 1994 through 1995, we experienced a total of 14 cases who were suspected as having ascariasis. They were characterized by peripheral blood eosinophilia (30-70%), high serum titers against Ascaris antigen, and most notably, they were absolutely negative for Ascaris eggs in repeated fecal examinations. Specific antibody titers against Ascaris antigen correlated well with the degree of eosinophilia. All patients were living in narrow areas of Kyushu, Japan, where a lot of porcine farms were located. Most of the patients were asymptomatic and pointed out to have eosinophilia during follow-up studies of chronic diseases or in regular check-up. Only one patient had a clear sign of Löffler' s syndrome and another had subcutaneous eosinophilic granuloma. However, laboratory examinations revealed moderate liver dysfunction in 7 patients and pulmonary infiltrations in 5 patients. Based on circumstantial and serological evidence, these patients were diagnosed as having been infected with Ascaris lumbricoides suum, a swine Ascaris.
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Current status of Gnathostomiasis dorolesi in Miyazaki Prefecture, Japan
Nawa Y., Maruyama H., Ogata K.
Southeast Asian Journal of Tropical Medicine and Public Health 28 SUPPL. 1 11 - 13 1997年12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：Southeast Asian Journal of Tropical Medicine and Public Health
Gnathostomiasis is an important food-borne parasitic zoonosis caused mainly by ingesting uncooked or undercooked flesh of freshwater fishes. Although four distinct species of the genus Gnathostoma were identified as the causative agents for human gnathostomiasis, human infections with G. doloresi have been found only in Japan, concentrated in Miyazaki Prefecture. So far we have found 25 cases in Miyazaki Prefecture. Although most of these patients were of cutaneous gnathostomiasis, two patients presented to the hospital with unusual clinical manifestations ; one case was a pulmonary gnathostomiasis diagnosed by immunoserological methods, and the other was an ileus caused by migration of the late 3rd stage larva in the colonic tissue, which was found by post-operative histopathological examination. Although cutaneous lesions such as creeping eruption or mobile erythema are the common clinical features of gnathostomiasis. caution should be paid to the presence of such unusual cases.
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Maruyama H., Noda S., Choi W., Ohta N., Nawa Y.
Parasitology International 46 ( 3 ) 181 - 188 1997年10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
Fine binding specificities to Ascaris suum and A. lumbricoides antigens of the sera from patients with probable visceral larva migrans (VLM) due to A. suum infection were examined. Although multiple-dot enzyme-linked immunosorbent assay (ELISA) was found to be useful for the primary screening of patients, identification of the responsible species was sometimes difficult due to extensive cross reactions with other ascarid parasite antigens. Fine resolution to determine the causative pathogen was obtained by a rather classical Ouchterlony's double immunodiffusion test. The difference in the binding of the patients' sera to A. suum and A. lumbricoides antigens was also demonstrated by an inhibition ELISA. The patients' antibodies bound with higher avidity to the A. suum antigen than to the. A. lumbricoides and Toxocara canis antigens. Combination of at least two different immunological assay methods is recommended for the diagnosis of VLM due to ascarid parasites. © 1997 Elsevier Science Ireland Ltd.
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Li W., Berencsi K., Basak S., Somasundaram R., Ricciardi R., Gönczöl E., Zaloudik J., Linnenbach A., Maruyama H., Miniou P., Herlyn D.
Journal of Immunology 159 ( 2 ) 763 - 769 1997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：Journal of Immunology
The human colorectal carcinoma (CRC)-associated Ag CO17-1A/GA733, originally defined by mAbs CO17-1A and GA733, has been a useful target in passive immunotherapy of CRC patients with mAb and in active immunotherapy with anti-idiotypic Abs mimicking the CO17-1A or GA733 epitope. Both approaches have targeted single epitopes. We investigated the capacity of full-length CO17-1A/GA733 Ag expressing multiple potentially immunogenic epitopes and encoded by recombinant adenovirus 5 (Ad5 GA733-2) to induce humoral, cellular, and/or protective immunity in mice. Ad5 GA733-2 induced Ag-specific Abs that reacted predominantly to CO17-1A- and GA733-unrelated epitopes on the Ag and lysed Ag-positive CRC targets in conjunction with effector cells. Ad5 GA733-2-immune mice developed Ag-specific, proliferative lymphocytes of Th1 type and cytolytic lymphocytes. The use of Ad5 GA733-2 to immunize mice bearing established syngeneic CRC cells transfected with the human Ag induced significant and specific tumor regression. Cured mice resisted rechallenge with human CO17-1A/GA733 Ag-negative parental CRC cells, suggesting that targeting the human Ag on the murine transfectants induced protective immunity to other Ag expressed by the parental tumor. These results may explain the high potency of the recombinant vaccine. Thus, rAd5 GA733-2 may have potential as a vaccine for CRC patients.
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ミラルディア(Millardia meltada)における寄生虫特異抗体測定のためのELISA法(短報)
立石 美加, 堀井 洋一郎, 丸山 治彦, 名和 行文, 土屋 公幸, 牧村 進
The journal of veterinary medical science 59 ( 6 ) 491 - 494 1997年6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：社団法人日本獣医学会
ミラルディア(Millardia meltada)のIgG抗体をイムノアフィニティークロマトグラフィー法で精製し, ウサギ抗血清を作成した. この抗体を用いて, 寄生虫特異的ミラルデイア抗体をELISAにて測定したところ, 従来の方法に比べ著しい感度の上昇が認められた. ミラルデイアはStrongyloides venezuelensisとNippostrongylus brasiliensis感染に対して効率的な抗体産生を行っていることから, この動物の寄生虫に対する高感受性は一般的な免疫不全によるものではないと考えられる.
DOI： 10.1292/jvms.59.491
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Pereira S., Maruyama H., Siegel D., Van Belle P., Elder D., Curtis P., Herlyn D.
Journal of Immunological Methods 203 ( 1 ) 11 - 24 1997年4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 Immunological Methods
To establish a screening procedure for tumor cell-surface reactive Fabs, we used a model antigen/antibody system including the epidermal growth factor receptor (EGF-R) and the anti-EGF-R monoclonal antibody 425. The 425 Fab was displayed on the surface of M13 filamentous phage. In a screening assay for 425 phage binding to tumor cell surfaces, biotinylated 425-phage bound specifically to EGF-R-positive A431 epidermoid carcinoma cells and not to K562 non-expressor erythroleukemia cells. With a model library, the sensitivity of phage enrichment by phage binding to cell surfaces was one 425-phage in 20,000 unrelated phages after 4 rounds of panning on A431 cells. In a phage tissue screening assay, 425-phage, but not unrelated phage, bound specifically to melanoma cells expressing EGF-R. Epitope and idiotope specificity of 425-phage was demonstrated in phage competition assays, using as targets A431 cells and anti-idiotypic antibodies to monoclonal antibody 425, respectively. Finally, the EGF-R protein was directly isolated from A431 cell extracts, using biotinylated 425-phage. The data obtained with the 425 model library system demonstrate the usefulness of antibody phage display for the rapid identification and isolation of tumor or other disease-related cell surface antigens.
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A case report of pleural sparganosis
Tanaka S., Maruyama H., Ishiwata K., Nawa Y.
Parasitology International 46 ( 1 ) 73 - 75 1997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：Parasitology International
A rare form of sparganosis is reported. A 47-year-old man admitted with chest pain and pleural effusion was diagnosed immunologically as having sparganosis. He was successfully treated with praziquantel. © 1997 Elsevier Science Ireland Ltd.
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Maruyama H., Nawa Y.
Experimental Parasitology 85 ( 1 ) 10 - 15 1997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：Experimental Parasitology
Adult worms of Strongyloides venezuelensis were cultured in vitro. After overnight incubation, about 60% of the worms adhered firmly to the bottom of culture vessels by secreting adhesive substances from the mouth. A single worm produced 24.5 ± 10.1 of the adhesion spots overnight. When they were transferred to new culture vessels, they still produced new spots comparable to those produced for first 24 hr. The adhesion spots were positively stained with Coomassie brilliant blue and also with mucicarmine, periodic acid-Schiff, and alcian blue, pH 2.5, but not with alcian blue, pH 0.3, indicating their glycoprotein nature. The substances were amorphous and did not contain cells or nuclei. Histologic staining with a panel of lectins showed that the adhesive substances were rich in mannose, N-acetyl galactosamine, and N-acetyl glucosamine, but devoid of sialic acid. These characteristics were distinct from those of jejunal goblet cell mucins of rats. Adhesive substances contained antigenic components recognized by sera from infected rats. Thus, the adhesive substances secreted from the mouth of S. venezuelensis were clearly of parasite origin. We consider the production/secretion of the adhesive substances by S. venezuelensis adult worms a key step for the parasites to invade and establish the host epithelial layer.
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Case report: Eosinophilic colitis with high antibody titre against Ascaris suum
Takeyama Y., Kamimura S., Suzumiya J., Oh K., Okumura M., Akahane H., Maruyama H., Nawa Y., Ohkawara T., Kikuchi M.
Journal of Gastroenterology and Hepatology (Australia) 12 ( 3 ) 204 - 206 1997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：Journal of Gastroenterology and Hepatology (Australia)
Eosinophilic gastroenteritis (EGE) is an inflammatory disease characterized by eosinophilic infiltration of the gastrointestinal tract accompanied by varying abdominal symptoms and usually by peripheral blood eosinophilia. Although the precise aetiology of EGE remains to be determined, contribution of allergic process to certain allergens, such as foods, drugs and parasites, has been repeatedly proposed as the pathogenesis of the disease. Here we report on a rare case of a woman who had extensive eosinophilic infiltration in the descending and rectal colon with a high titre of IgG antibody against Ascaris suum. The patient was successfully treated with prednisolone.
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Combinatorial antibodies against human malignant melanoma 国際共著
Pereira S., Van Belle P., Elder D., Maruyama H., Jacob L., Sivanandham M., Wallack M., Siegel D., Herlyn D.
Hybridoma 16 ( 1 ) 11 - 16 1997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：Hybridoma
The general responsiveness of human melanoma to immunotherapy has been well established, but active immunotherapy of melanoma has been hampered by insufficient information on the immunogenicity of melanoma antigens in patients. We have attempted to identify melanoma-associated antigens recognized by patients' B cells using an antibody phage display approach. Antibody display on filamentous phages allows direct screening of cDNA libraries for expression of cell-surface-reactive antibodies, without the need for antibody production and purification using bacteria or eukaryotic cell systems. This approach was used to identify melanoma-associated cell- surface antigens recognized by patients' B cells. Antibodies produced by the B cells of a melanoma patient (in remission for >7 years following periodic vaccination with allogeneic melanoma cell vaccine) were displayed as Fabs on the surfaces of filamentous phages. A library of 108 phages was absorbed to normal melanocytes, followed by phage binding to and elution from melanoma cells (human lymphocyte antigen nonmatched and vaccine melanoma cells). Phages were further selected for reactivities with tunicamycin-treated melanoma cells. These procedures resulted in a >106-fold enrichment of tumor-specific phages from the original phage library. One phage-Fab bound to melanoma cells, other tumor cells, and a few normal cells in cultured cell lines and in tissue sections.
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Anti-idiotype cancer vaccines: Past and future
Herlyn D., Somasundaram R., Li W., Maruyama H.
Cancer Immunology Immunotherapy 43 ( 2 ) 65 - 76 1996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：Cancer Immunology Immunotherapy
Anti-idiotypic antibodies (Ab2) binding to the antigen-combining site of antitumor antibodies (Ab1) can induce anti-anti-idiotypic antibodies (Ab3) that specifically bind to the tumor antigen recognized by Ab1. Furthermore, Ab2, mimicking tumor antigens, have been shown to induce anti-anti-idiotypic proliferative T lymphocytes of the helper and suppressor type, as well as cytotoxic lymphocytes. The immunomodulatory activities of Ab2 have been demonstrated both In animals and in patients. The demonstration of tumor growth inhibition by anti-idiotypes in preclinical and phase I clinical studies emphasizes that randomized control trials should be performed to demonstrate clinical efficacy of Ab2 vaccines.
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Owhashi M., Maruyama H., Nawa Y.
International Journal for Parasitology 26 ( 7 ) 705 - 711 1996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：International Journal for Parasitology
Kinetic changes of eosinophil chemotactic factor (ECF) production from granulomas, splenic T-cells or mast cells were examined with reference to granuloma formation around newly deposited single eggs in Schistosoma japonicum-infected mice. The peri-ovular granulomas began to appear at around 5 weeks post-infection (p.i.). Their size reached a peak at 6 weeks and then decreased gradually. Up to 8 weeks p.i., eosinophils were the predominant cell type in the granulomas. ECF-release from isolated granulomas paralleled the size of granulomas. Circulating ECF-A, which was assumed to be derived from mast cells, was also detected 6 weeks afterwards in parallel with the level of specific IgE antibody level against egg antigens in the serum. The circulating ECF-A peaked at 8 Necks and decreased after 10 weeks. Spleen cells began to produce ECF specific to bone-marrow eosinophils began at 5 weeks p.i., reached a peak at 6 weeks and then decreased rapidly. On the other hand, the production of ECF specific to eosinophils obtained from the peritoneal cavity began at 6 weeks and decreased rapidly thereafter. These results suggest that various kinds of host-derived ECFs seem to contribute, in one way or an other, to tile accumulation of eosinophils in and around granulomatous lesions. The possible role of these ECFs in eosinophil mobilization from the site of production to the inflamed site is discussed.
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Emerging Problems of Parasitic Diseases in Southern Kyusyu, Japan
丸山 治彦, 野田 伸一, 名和 行文
寄生虫学雑誌 = Japanese journal of parasitology 45 ( 3 ) 192 - 200 1996年6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：日本寄生虫学会
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Fascioliasis Cases Recently Found in the Southern Part of Kyushu District, Japan
丸山 治彦, 野田 伸一, 三森 龍之, 名和 行文
寄生虫学雑誌 = Japanese journal of parasitology 45 ( 3 ) 247 - 254 1996年6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：日本寄生虫学会
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Itoh H., Murakumo Y., Tomita M., Ide H., Kobayashi T., Maruyama H., Horii Y., Nawa Y.
Biochemical Journal 314 ( 3 ) 923 - 929 1996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：Biochemical Journal
By using the combination of reverse-transcription PCR and rapid amplification of cDNA ends methods, two distinct cDNAs encoding mast-cell proteases (chymases; MCPs), designated as gMCP-1 and -2, were successfully cloned and sequenced from the jejunum of Mongolian gerbil, Meriones unguiculatus, infected with Nippostrongylus brasiliensis. On the basis of a comparison of the deduced amino acid sequences with those of known rodent mast-cell chymases, gMCP-1 was found to be highly similar to mouse mast-cell protease (mMCP)-4 and rat mast-cell protease (rMCP)-1, while gMCP-2 was similar to mMCP-5 and rMCP-3: Although mMCP-4 and -5 and rMCP-1 and -3 were restrictedly or mainly expressed in connective-tissue mast cells and serosal mast cells, the gMCP-1 and -2 genes were mainly transcribed in the jejunal mucosa and to a lesser extent in the skin and tongue. Moreover, kinetic study after infection revealed that the amounts of the gMCP-1 and -2 mRNAs in jejunum paralleled well the degree of intestinal mastocytosis. The expression of gMCP-1 and -2 in mucosal mast cells of gerbil jejunum was also confirmed by in situ hybridization. Since a tryptase, another type of MCP, was also expressed in mucosal mast cells of gerbils but not in those of mice and rats, the expression of MCPs in mucosal mast cells of gerbils is different from those of mice and rats. The Mongolian gerbil would be a useful model with which to investigate the physiopathological role of MCPs.
DOI： 10.1042/bj3140923
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Maruyama H., Benden A., Weiping L., Zaloudik J., Koido T., Taupin J., Acres B., Somasundaram R., Prewett M., Herlyn D.
International Journal of Cancer 65 ( 4 ) 547 - 553 1996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：International Journal of Cancer
Anti-idiotypic antibodies (Ab2) that bind to the antigen-combining region of anti-tumor antibodies (Ab1) may functionally, and even structurally, mimic tumor antigen. We have previously demonstrated that polyclonal goat Ab2 directed against anti-human gastrointestinal carcinoma Ab1 GA733 induces anti-anti-idiotypic antibodies (Ab3) in animals that are Ab1-like in their binding specificity and idiotope expression. To obtain more defined Ab2 vaccines with potentially increased specificity and efficacy, a monoclonal Ab2 (FG1) was produced against Ab1 GA733 in rats. The monoclonal Ab2 FG1, similar to the polyclonal Ab2 described previously, induced Ab3 in rabbits that were Ab1-like in their idiotope expression and binding specificity to tumor cells and antigen. Antigen-specific Ab3 induced by Ab2 FG1 were easily detected in unprocessed rabbit sera, whereas the demonstration of such Ab3 after polyclonal Ab2 immunization required purification of the Ab3 from the rabbit sera. In addition, Ab2 FG1 induced antigen specific humoral and cellular immunity in mice. Murine Ab3 bound specifically to antigen-positive tumor cells. Ab2-immunized mice showed antigen-specific delayed-type hypersensitivity (DTH) reaction, and cultured splenocytes from the immune mice demonstrated specific proliferation and cytokine (interferon-γ and interleukin-4) secretion upon stimulation with GA733 antigen. However, immune mice were not protected against a challenge with syngeneic GA733 antigen-expressing colon carcinoma cells.
DOI： 10.1002/(SICI)1097-0215(19960208)65:4<547::AID-IJC25>3.0.CO;2-5
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Eosinophil peroxidase deficiency in new zealand white mice
Ohmori J., Tokunaga H., Ezaki T., Maruyama H., Nawa Y.
International Archives of Allergy and Immunology 111 ( 1 ) 30 - 35 1996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：International Archives of Allergy and Immunology
Eosinophil peroxidase (EPO) is one of the granule enzymes in the eosinophil-specific granules and is distinct from myeloperoxidase. Here we report that peroxidase activity was absent in eosinophils of New Zealand White (NZW) mice. When NZW, New Zealand Black and their F, mice were treated with cyclophosphamide followed by Toxocara canis infection, the kinetic changes in the number of eosinophils in peripheral blood, determined by counting in Hinkelman’s diluting fluid, were almost comparable among the three strains. However, when their blood films were stained for peroxidase reaction, eosinophils of NZW mice, but not of the other strains, lacked EPO activity, though their specific granules were stained by eosin Y Sudan black staining for phospholipid was also negative in eosinophils of NZW mice. EPO deficiency in NZW eosinophils was further confirmed by electron-microscopic observations and by measuring EPO activity in the extracts of eosinophil-rich cell suspensions. These results indicate that NZW eosinophils share most of the features with human EPO-deficient eosinophils, suggesting that the NZW mouse is a murine counterpart of human EPO deficiency. © 1996 S. Karger AG, Basel.
DOI： 10.1159/000237341
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Expression of inter-α-trypsin inhibitor light chain (bikunin) in human pancreas
Itoh H., Tomita M., Kobayashi T., Uchino H., Maruyama H., Nawa Y.
Journal of Biochemistry 120 ( 2 ) 271 - 275 1996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：Journal of Biochemistry
Expression of inter-α-trypsin inhibitor light chain (ITI-LC, also known as bikunin or urinary trypsin inhibitor) was examined in various human tissues. By reverse-transcription polymerase chain reaction, the mRNA was detected not only in the liver, a known site of ITI-LC production, but also in the kidney, heart, lung, and pancreas. By RNA blot analysis, the mRNA was also detected in the pancreas and liver, but not in the kidney, heart, or lung. The ITI-LC protein was immunohistochemically detected along the surface of pancreatic acinar cells. These results indicate the apparent expression of the gene for ITI-LC in the pancreas. ITI-LC protein on the surface of pancreatic acinar cells may play an important role in preventing autodigestion by exocrine enzymes such as trypsinogen and chymotrypsinogen.
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Cdna sequencing and expression of rat mast cell tryptase
Ide H., Itoh H., Tomita M., Murakumo Y., Kobayashi T., Maruyama H., Osada Y., Nawa Y.
Journal of Biochemistry 118 ( 1 ) 210 - 215 1995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：Journal of Biochemistry
A cDNA encoding rat mast cell tryptase (rMCT) was successfully cloned, and sequenced, from peritoneal cells of Lewis rats infected with Nippostrongylus brasiliensis by the reverse transcription-polymerase chain reaction and repid amplification of cDNA ends methods. The cDNA was 1, 097 base-pairs long, and included 822 base-pairs of an open reading frame. As judged from the deduced amino acid sequence, rMCT is highly homologous to mouse mast cell protease-6, and is considered to be translated as a prepro-enzyme with a 19 ami no acid signal peptide, a 10-ami no acid activation peptide, and a 245-amino acid mature enzyme. The rMCT mRNA was not detected in peritoneal cells of mast cell-deficient Ws/Ws rats, though it was strongly detected in oncs of littermate +/+ and Lewis rats. In addition to in peritoneal mast cells, the rMCT mRNA was detected in the tongue. However, mRNA signals were not detected in the small intestine regardless of N. brasiliensis infection. Nor were mRNA signals detected in RBL2H3 rat basophilic leukemia cells. In the lung, the rMCT mRNA was strongly detected after infection with N. brasiliensis though it was only faintly detected before infection. These results suggest that the rMCT is basically specific for connective tissue mast cells, but not for mucosal mest cells and that it is up-regulated in the lung during the inflummatory process of a parasitic infection. © 1995 by the Journal of Biochemistry.
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SOMASUNDARAM R., JACOB L., ADACHI K., CLASS R., SCHECK S., MARUYAMA H., HERLYN D.
Scandinavian Journal of Immunology 41 ( 4 ) 384 - 390 1995年4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：Scandinavian Journal of Immunology
Mice lacking functional T and B lymphocytes offer an in vivo animal model for the study of human immune functions. We have attempted to optimize the reconstitution of severe combined immunodeficiency (SCID) mice with human peripheral blood lymphocytes (PBL) using radiation, anti‐asialo GM 1 antibody or cyclophosphamide (Cy) treatment of the mice and in vitro stimulation of human PBL with interleukin (IL)‐2 prior to their transfer to the mice. Total human IgG and tetanus‐toxoid (TT)‐specific human IgG responses of the mice were used as parameters of successful reconstitution. Treatment of the mice with anti‐asialo GM 1 antibody significantly enhanced total human IgG levels, but not TT‐specific antibody responses, whereas irradiation or Cy treatment of the mice had no effect on human antibody production. In vitro treatment of human PBL with IL‐2 prior to engraftment significantly decreased total human IgG responses of human PBL‐grafted SCID mice. The immune responses of individual mice within a group were highly variable, which constitutes a major disadvantage of this model. Copyright © 1995, Wiley Blackwell. All rights reserved
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Molecular cloning of mouse intestinal trefoil factor and its expression during goblet cell changes
Tomita M., Itoh H., Ishikawa N., Higa A., Ide H., Murakumo Y., Maruyama H., Koga Y., Nawa Y.
Biochemical Journal 311 ( 1 ) 293 - 297 1995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：Biochemical Journal
A cDNA encoding mouse intestinal trefoil factor (mITF) was successfully cloned and sequenced from the small intestine of C57BL/6 mouse by using the combination of reverse transcription-PCR and rapid amplification of cDNA ends methods. The gene was, similar to rat and human ITFs, mainly expressed in the small and large intestine. The mITF expression was up-regulated during the recovery phase after depletion of goblet cells in acetic acid-induced colitis. On the other hand, the expression in the jejunum was not altered, while goblet cell hyperplasia was induced by Nippostrongylus brasiliensis infection. These results suggest that the mITF expression did not simply correlate with the number of goblet cells. The mITF may play an important role in the maintenance and repair of mucosal function of the rectum. Additionally, the mITF in the jejunum may play a role in alteration of the physicochemical nature of goblet cell mucins, thereby affecting the establishment of intestinal helminths.
DOI： 10.1042/bj3110293
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Murakumo Y., Ide H., Itoh H., Tomita M., Kobayashi T., Maruyama H., Horii Y., Nawa Y.
Biochemical Journal 309 ( 3 ) 921 - 926 1995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：Biochemical Journal
By using the combination of reverse-transcription PCR and rapid amplification of cDNA ends methods, a cDNA encoding mast cell tryptase was successfully cloned from the small intestine of Mongolian gerbil, Meriones unguiculatus, infected with Nippostrongylus brasiliensis. The cDNA was 1219 bp long including 810 bp of an open reading frame, Based on the deduced amino acid sequences of known mast cell tryptases of other species, the gerbil mast cell tryptase (gMCT) was highly similar to mouse mast cell protease (mMCP)-7, and seems to be translated as a prepro-enzyme with 25 amino acids of signal and activation peptides and 245 amino acids of mature enzyme. The gMCT mRNA was preferentially transcribed in the intestinal mucosa and to a far lesser extent in the connective tissue such as skin and tongue. Moreover, kinetic study after infection revealed that the amount of gMCT mRNA in the small intestine correlated well with the degree of intestinal mastocytosis. Throughout the course of infection, enzyme-histochemically detectable tryptase activity was limited to mucosal mast cells. Since mucosal mast cells of other rodents, including mice and rats, do not express tryptases, this is the first report of rodent mast cell tryptase expressed in the intestinal mucosa.
DOI： 10.1042/bj3090921
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Ide H., Itoh H., Tomita M., Murakumo Y., Kobayashi T., Maruyama H., Osada Y., Nawa Y.
Biochemical Journal 311 ( 2 ) 675 - 680 1995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：Biochemical Journal
A cDNA encoding a novel rat mast-cell proteinase (MCP) named rMCP-3 was successfully cloned and sequenced from the peritoneal cells of Lewis rats infected with the intestinal nematode Nippostrongylus brasiliensis by using the combination of reverse transcription-PCR and rapid-amplification-of-cDNA-ends ('RACE') methods. The cDNA was 979 bp long and included a 741 bp open reading frame. When the deduced amino acid sequence was compared with those of other known mast-cell proteinases, rMCP-3 was considered to be translated as a preproenzyme with a 19-amino-acid signal peptide, a two-amino-acid activation peptide and a 226-amino-acid mature enzyme. The amino acid identity in the mature enzyme was 52.9% and 55.1% with rMCP-1 and rMCP-2 respectively. The rMCP-3 mRNA was not detected in the peritoneal cells of mast-cell-deficient Ws/Ws rats, though it was strongly detected in those of littermate +/+ and Lewis rats, indicating the mast-cell origin of rMCP-3. In addition to being present in peritoneal mast cells, the rMCP-3 mRNA was strongly detected in the skin, tongue, and RBL2H3 rat basophilic leukaemia cells and weakly in the jejunum of N. brasiliensis-infected rats by RNA blot analysis using a rMCP-3 gene-specific probe. By reverse transcription-PCR, the rMCP-3 mRNA was also detected in the lung. While the expression of rMCP-1 and rMCP-2 are clearly restricted in connective-tissue mast cells and mucosal mast cells respectively, rMCP-3 was widely expressed in both types of mast cells with a predominance in connective-tissue mast cells.
DOI： 10.1042/bj3110675
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Seguchi K., Matsuno M., Kataoka H., Kobayashi T., Maruyama H., Itoh H., Koono M., Nawa Y.
American Journal of Tropical Medicine and Hygiene 53 ( 3 ) 263 - 266 1995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：American Journal of Tropical Medicine and Hygiene
Gnathostomiasis is primarily a disease of the skin characterized as creeping eruption or mobile erythema. However, larval Gnathostoma sometimes migrate into an unexpected site to elicit serious illness. Here we describe a case of colonic ileus caused by Gnathostoma doloresi. The patient was a 57- year-old man living in Miyazaki Prefecture, Japan, which is known as an area endemic for this parasite. One week after having eaten a few slices of the flesh of a snake (Agkistrodon halys), he developed severe abdominal pain. An abdominal radiograph revealed multiple gas-fluid levels with a distended bowel of an inverted U shape. A barium enema revealed a tumor in the ascending colon near the hepatic flexure that was surgically removed by simple colonic resection. An oblique section of a parasite surrounded by massive infiltration of eosinophils was found by postoperative histopathologic examination. The entire body of the advanced third-stage larva of G. doloresi was dissected from a specimen-embedded paraffin block.
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Herlyn D., Harris D., Zaloudik J., Sperlagh M., Maruyama H., Jacob L., Kieny M., Scheck S., Somasundaram R., Hart E., Ertl H., Mastrangelo M.
Journal of Immunotherapy 15 ( 4 ) 303 - 311 1994年5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 Immunotherapy
Monoclonal anti-idiotypic antibody (Ab2) VF2 was derived from rats immunized with anti-colorectal carcinoma (anti-CRC) monoclonal antibody (Abl) CO17–1A. In rabbits the Ab2 induced anti anti-idiotypic antibodies (Ab3) that shared idiotopes with the Abl, bound to the same epitope on CRC cells as Abl, and bound to the isolated CO17–1A antigen. Monoclonal Ab2 VF2 was superior to the previously described polyclonal goat Ab2 against Abl CO17–1A in its capacity to elicit humoral immunity in animals. Ab2 VF2 also induced a specific delayed-type hypersensitivity (DTH) response to challenge with irradiated CO17–1A antigen-positive human CRC cells in mice. Of nine CRC patients immunized with aluminum hydroxide-precipitated Ab2 VF2, six developed antibodies that bound to Ab2, but only three patients developed Ab3 that bound to idiotypic determinants on Ab2. However, the Ab3 did not bind to CO17–1A antigen-positive CRC cells. In contrast, in a previously described trial with polyclonal goat Ab2 to Abl CO17–1A, most of the patients developed anti-CRC antibodies. Four of the nine patients immunized with Ab2 VF2 developed DTH responses to intradermal challenge with the Ab2, and in one patient DTH was both Ab2− and antigen-specific. Peripheral blood mononu-clear cells of the four DTH-reactive patients did not proliferate in response to in vitro stimulation with either Ab2 or antigen. These studies demonstrate that the immunomodulatory activity of monoclonal Ab2 VF2 in animals is only in part predictive of its activity in patients. © 1984 Journal of Immunotherapy. All rights reserved.
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Polyclonal antiidiotypic antibodies mimicking gp 120 of HIV-1
Sperlagh M., Hoxie J., Maruyama H., Stefano K., Gonzales-Scarano F., Prewett M., Liang S., Matsushita S., Herlyn D.
Viral Immunology 7 ( 2 ) 61 - 69 1994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：Viral Immunology
Rabbit antiidiotypic antibodies (Ab2) were produced against anti-HIV-1 antibody 0.5β (Ab1), which binds to gp120 of HIV-1 and shows virus-neutralizing activity. The Ab2 bound specifically to the Ab1 and their binding to Ab2 was inhibited by a recombinant fragment of gp120 (PB1) or a peptide (residues 301-324 of gp120), both expressing the Ab1-defined epitope. The Ab2 induced in rats antiantiidiotypic antibodies (Ab3) that were Ab1-like in their binding reactivities to PB1, native gp120 or peptide and shared idiotopes with the Ab1. However, the Ab2 did not induce virus-neutralizing Ab3, probably a reflection of the low avidity of the Ab3 as compared to the Ab1.
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Sperlagh M., Stefano K., Gonzalez-Scarano F., Liang S., Hoxie J., Maruyama H., Prewett M., Matsushita S., Herlyn D.
AIDS 7 ( 12 ) 1553 - 1559 1993年12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：AIDS
Objective: To develop effective, specific and safe anti-idiotypic antibody (Ab2) vaccines against HIV-1. Design: Murine monoclonal Ab2 were generated against anti-HIV-1 antibody 0.5β (Ab1), which binds to gp120, neutralizes HIV-1 and inhibits virus-induced syncytia formation. Methods: Mice were immunized with Ab1, and Ab2 were produced from immunized mice by the hybridoma technique. The Ab2 were characterized in vitro, injected into rabbits, and the anti-anti-idiotypes (Ab3) induced in the rabbits were analyzed for binding and antiviral reactivities by enzyme-linked immunosorbent assay, p24gag release and syncytia formation assays. Results: Seven Ab2 bound to the antigen-combining site of Ab1, one of which (UD7) induced Ab3 in rabbits that were Ab1-like in their binding reactivities to PB1 (recombinant gp120 fragment) or peptides of gp120, and shared idiotypes with the Ab1. Crude Ab3-containing sera specifically and effectively neutralized the virus. Conclusion: Monoclonal Ab2 UD7 has potential as a vaccine against HIV-1.
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Makoto O., Shiroh F., Kouki K., Yoichiro H., Haruhiko M., Hiromi H., Yukifumi N.
Molecular Immunology 30 ( 14 ) 1315 - 1320 1993年10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：Molecular Immunology
To compare the molecular structure of a parasite-derived neutrophil chemotactic factor (NCF) with host-derived NCFs or other NCFs, molecular cloning of cDNA encoding NCF derived from Dirofilaria immitis adult worm (DiNCF) was performed. A D. immitis cDNA library was screened with an antibody to DiNCF, and one DiNCF cDNA clone (pD-4) was isolated. A fusion protein of pD-4 and gene 10 protein showed significant neutrophil chemotactic activity whereas gene 10 protein itself showed marginal neutrophil chemotactic activity. The total nucleotide sequence analysis revealed that pD-4 was 994 bp long with a 432 bp open leading frame encoding a 143 residue protein. The NH 2 -terminal amino acid sequence of the natural DiNCF and the deduced amino acid sequence from the cDNA showed that the mature functional protein was comprised of 112 amino acids. Although the deduced amino acid sequence of this protein did not show overall homology to host-derived NCFs or other known proteins, it contained a similar sequence (Met-Phe-Lys) to the known chemotactic peptides. The possibility of the functional epitope of DiNCF is discussed. © 1993.
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Levi M., Sällberg M., Rudén U., Herlyn D., Maruyama H., Wigzell H., Marks J., Wahren B.
Proceedings of the National Academy of Sciences of the United States of America 90 ( 10 ) 4374 - 4378 1993年5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：Proceedings of the National Academy of Sciences of the United States of America
A complementarity-determining region (CDR) of the mouse monoclonal antibody (mAb) F58 was constructed with specificity to a neutralization-inducing region of human immunodeficiency virus type 1 (HIV-1). The mAb has its major reactivity to the amino acid sequence I - GPGRA in the V3 viral envelope region. All CDRs including several framework amino acids were synthesized from the sequence deduced by cloning and sequencing mAb F58 heavy- and light-chain variable domains. Peptides derived from the third heavy-chain domain (CDR-H3) alone or in combination with the other CDR sequences competed with F58 mAb for the V3 region. The CDR-H3 peptide was chemically modified by cyclization and then inhibited HIV-1 replication as well as syncytium formation by infected cells. Both the homologous IIIB viral strain to which the F58 mAb was induced and the heterologous SF2 strain were inhibited. This synthetic peptide had unexpectedly potent antiviral activity and may be a potential tool for treatment of HIV-infected persons.
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Molecular cloning of murine monoclonal anti-idiotypic Fab
Kasai Y., Herlyn D., Sperlagh M., Maruyama H., Matsushita S., Linnenbach A.
Journal of Immunological Methods 155 ( 1 ) 77 - 89 1992年10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 Immunological Methods
Anti-idiotypic antibodies (Ab2) binding to idiotopes on antibodies with various antigen binding specificities (Ab1) are potential regulators of immunity in a variety of diseases, such as autoimmunity, cancer, and viral, bacterial, or parasitic infections. Furthermore, Ab2 are useful probes for the characterization of receptor/ligand interactions. Thus far, Ab2 production has been limited to the isolation of polyclonal Ab2 from immune sera or monoclonal Ab2 from hybridoma supernatants. However, both approaches have produced a limited number of Ab2. As an alternative approach, we demonstrate here the production of Ab2-Fab by using repertoire cloning. Using HIV-1 as a model system, the Ab2-Fab were generated from the spleens of mice immunized with the virus-neutralizing and syncytia-inhibiting anti-HIV-1 monoclonal antibody 0.5β. A bacteriophage γ vector system was used to express a combinatorial library in Escherichia coli. Iodinated 0.5β was used to identify 17 Ab2-Fab clones. DNA sequence analysis of five clones revealed three similar κ and Fd combinations. The Ab2-Fab bound with high affinity (3.5-6.5 × 109 liters/mol) specifically to the Ab1 and not to isotype-matched antibodies with unrelated specificities. The three Ab2-Fab probably bind to the same idiotope on the Ab1 as demonstrated in cross-competition binding studies. The Ab2-Fab inhibited binding of the Ab1 to antigen, and therefore, may functionally mimic the epitope defined by the Ab1. Repertoire cloning of Ab2-Fab may facilitate the generation of Ab2 that have potential as modulators of immune responses against various antigens. © 1992.
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Hepatic eosinophilopoiesis from multipotent hemopoietic stem cells in Toxocara canis-infected mice
Maruyama H., Higa A., Asami M., Owhashi M., Nawa Y.
Experimental Hematology 19 ( 2 ) 77 - 80 1991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：Experimental Hematology
Extramedullary hemopoiesis, recognized as hemopoietic foci, increased in the livers of Toxocara canis-infected mice. At the peak of the response (day-13 after infection), the majority of hepatic hemopoietic foci were of the eosinophil lineage. Hepatic nonparenchymal cells prepared from T. canis-infected mice on day 13 contained large numbers of hemopoietic stem cells, more than half of which were cycling. When W/W(v) mice, which are genetically deficient in multipotent hemopoietic stem cells, were infected with T. canis, hepatic hemopoietic foci were rare throughout the course of infection. This impaired response of W/W(v) mice was restored by bone marrow grafting from normal +/+ littermates. These results indicate that, in response to the increased demand, eosinophils are generated in the liver by the differentiation from multipotent stem cells, not only from the committed precursors.
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Maruyama H., Higa A., Asami M., Owhashi M., Nawa Y.
Parasitology Research 76 ( 6 ) 461 - 465 1990年6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 Research
Extramedullary hemopoiesis recognized as hemopoietic foci increased in the liver of Schistosoma japonicum-infected mice in parallel with kinetic changes in periovular granuloma formation. At the peak of the response, about 65% of the hepatic hemopoietic foci were of eosinophil lineage. When S. japonicum-infected mice were irradiated, hepatic hemopoietic foci rapidly disappeared within 3 days, whereas inflammatory cells in the periovular granulomas slowly reduced in number. When the number of hemopoietic stem cells in the liver were examined by spleen-colony assay, kinetic changes in the number of hemopoietic stem cells in hepatic nonparenchymal cells paralleled those of hepatic hemopoietic foci. Hemopoietic stem cells were rare in the granuloma cells. These results indicate that in response to the increased demand for eosinophils and other inflammatory cells, the liver acts as an extramedullary hemopoietic organ in which inflammatory cells are generated from hemopoietic stem cells. © 1990 Springer-Verlag.
DOI： 10.1007/BF00931050
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Owhashi M., Horii Y., Ikeda T., Maruyama H., Abe T., Nawa Y.
International Archives of Allergy and Immunology 92 ( 1 ) 64 - 68 1990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：International Archives of Allergy and Immunology
The role of mast-cell-derived eosinophil chemotactic factor A (ECF-A) on eosinophil-rich peri-ovular granuloma formation was examined by using mast-cell-deficient WBB6F1-W/W mice infected with Schistosoma japonicum. The average size of granulomas formed around newly deposited eggs in the liver of W/W<sup>v</sup> mice was significantly smaller than that observed in control +/+ mice. The number of adult worms recovered or specific IgE titers were comparable between W/W<sup>v</sup> and +/+ mice. In contrast, immediate-type hypersensitivity response to specific antigen and dialyzable low-molecular weight ECF in the serum was detectable only in infected +/+ mice. When naive bone marrow eosinophils were incubated with the dialyzable fraction of infected +/+ mice sera, chemotactic reactivity of eosinophils to ECF derived from S. japonicum eggs was significantly enhanced, although that to synthetic ECF-A was depressed. Similar effects were observed when naive eosinophils were treated with synthetic ECF-A. The dialyzable fraction of infected W/Wv mice sera had no such modulating effect on the chemotactic reactivity of eosinophils. These results suggest that an immediate-type hypersensitivity reaction is important in the formation of eosinophilic granulomas around S. japonicum eggs, mainly through the modulating effect of mast-cell-derived ECF-A on the chemotactic reactivity of eosinophils. © 1990 S. Karger AG, Basel.
DOI： 10.1159/000235226
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Effects of toxocara canis infection on hemopoietic stem cells and hemopoietic factors in mice
Higa A., Maruyama H., Abe T., Owhashi M., Nawa Y.
International Archives of Allergy and Immunology 91 ( 3 ) 239 - 243 1990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：International Archives of Allergy and Immunology
The effects of Toxocara canis infection on hemopoietic stem cells and hemopoietic factors were examined in mice. Severe eosinophilia was observed with a peak 14 days after infection. When the numbers of hemopoietic stem cells in peripheral blood, spleen, and bone marrow were examined by spleen colony assay (CFU-S), those in peripheral blood and spleen increased in parallel with peripheral blood eosinophilia. On the other hand, CFU-S in bone marrow did not alter significantly throughout the course of infection. Interleukin (IL)-3, which is known as multi-colony-stimulating factor and is involved in the growth/differentiation of various blood cells including stem cells, was produced by spleen cells of infected mice. The time course study showed that concanavalin A stimulated IL-3 production peaked on day 7 after infection, whereas that with excretory secretory antigen peaked on day 14. Even without stimulation, spleen cells obtained on day 21 after infection produced IL-3 spontaneously. IL-5, which is known to have eosinophil differentiation factor activity, was also produced by spleen cells obtained on day 13 after infection. These results suggest that in response to increased demand for eosinophils, hemopoietic stem cells migrate into various extramedullar hemopoietic organs where they grow/differentiate into mature eosinophils, depending on the hemopoietic factors. © 1990 S. Karger AG, Basel.
DOI： 10.1159/000235123
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NAWA Y., ABE T., IMAI J., MARUYAMA H.
Parasite Immunology 10 ( 2 ) 117 - 126 1988年3月
担当区分：最終著者 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：Parasite Immunology
Summary The susceptibility of C57BL/6‐bgJ/bgJ mice, which exhibit a murine counterpart of the Chediak‐Higashi syndrome, to infection with Strongyloides ratti was examined. After a primary infection, the peak of the daily larval output in faeces (LPG) of bgJbgJ mice was approximately twice as high as that of their littermate bgJ/+ mice. The total number of tissue migrating larvae recovered from bgJ/bgJ mice at 36 h after infection was also approximately twice as high as that from bgJ+mice. However, after a primary infection, bgJ/bgJ mice could completely expel adult worms in the intestine by day 14. When an equal number of tissue migrating larvae obtained from the head of +/+ mice were implanted into bgJ/bgJ and bgJ/+ mice, the magnitude and the kinetics of LPG were comparable between them, indicating that in both groups implanted larvae established in the intestine lo become adult worms and then they were expelled by day 13. Thus, immune mechanisms involved in worm expulsion of bgJ/bgJ mice were comparable to those of bgJ/+mice. The higher susceptibility of bgJ/bgJ mice could be reduced to the level of bgJ/+ mice by bone marrow grafting from bgJ/+mice 6 weeks prior to infection. Furthermore, when lethally irradiated bgJ/bgJ mice or bgJ/+mice were reconstituted with either type of bone marrow cells, the mice given bgJ/bgJ bone marrow cells showed higher susceptibility to infection with S. ratti regardless of the genotype of the recipients. These results indicate that the impaired natural defence of bgJ/bgJ mice is predetermined at the level of haemopoietic stem cells. Copyright © 1988, Wiley Blackwell. All rights reserved
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Owhashi M., Maruyama H., Nawa Y.
Infection and Immunity 55 ( 9 ) 2042 - 2046 1987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：Infection and Immunity
Granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by splenic lymphocytes obtained from Schistosoma japonicum-infected mice was partially purified by a combination of DEAE anion-exchange chromatography, concanavalin A-Sepharose affinity chromatography, and high-pressure liquid chromatography. When this partially purified GM-CSF was added to the culture of isolated intact granulomas, eosinophil chemotactic factor (ECF) lymphokine production by granulomas was significantly enhanced. The partially purified GM-CSF also enhanced ECF lymphokine production by granuloma T cells cocultured with syngeneic macrophages and specific antigen. The partially purified GM-CSF itself had neither ECF activity nor a synergistic effect with ECF lymphokine. When normal splenic macrophages were preincubated with the partially purified GM-CSF, they potentiated the ECF production by granuloma T cells under the presence of specific antigen. Augmentation of ECF lymphokine production by partially purified GM-CSF was further confirmed by using T-cell clones that were established from granuloma T cells. These results suggest that T-cell-derived GM-CSF primarily activate macrophages so that these activated macrophages can cooperate more effectively with T lymphocytes to produce ECF. Such potentiation of macrophage-T-cell interaction by GM-CSF may be important in the mechanisms of granuloma formation during an acute stage of schistosomiasis.
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Owhashi M., Maruyama H., Nawa Y.
Infection and Immunity 54 ( 3 ) 723 - 727 1986年12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：Infection and Immunity
Eosinophil chemotactic factor (ECF) was detected in the culture supernatant of isolated intact egg granulomas from the livers of Schistosoma japonicum infected mice. This factor had an apparent molecular weight of 15,000 by high-pressure liquid chromatography with an SW3000 column and bound to concanavalin A-Sepharose 4B. When cells obtained by enzymatic digestion of isolated granulomas were cultured under the presence of soluble egg antigen of S. japonicum or concanavalin A, ECF was also detected in the conditioned medium. The physicochemical nature of the ECF produced by concanavalin A-stimulated granuloma cells was similar to that produced by isolated intact granulomas. The ECF-producing activity of the cells was abolished by pretreatment with anti-Thy-1.2 or anti-Lyt-1.2 monoclonal antibody and complement but not by anti-Lyt-2.2 antibody. Furthermore, nylon wool-passed, T-enriched granuloma cells required collaboration of syngeneic macrophages to produce ECF. These results suggest that Lyt-1-positive T cells in the granuloma could, in collaboration with macrophages, produce ECF and thereby attract eosinophils to this lesion.