論文 - 丸山 治彦
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Research on calpain of Schistosoma japonicum as a vaccine candidate 査読あり
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：英語 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 査読あり 国際共著
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：英語 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：英語 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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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：英語 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 査読あり
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：英語 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：英語 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 国際共著
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
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：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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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：英語 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：英語 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
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：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
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：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.