Tomoyuki Ogura

Publications (8)23.8 Total impact

• Article: Expression of Apoptosis in Placenta of Experimental Antiphospholipid Syndrome Mouse.

  Shanmugam Velayuthaprabhu, Hidehiko Matsubayashi, Toshitaka Sugi, Masato Nakamura, Yasuyuki Ohnishi, Tomoyuki Ogura, Govindaraju Archunan
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  ABSTRACT: PROBLEM: To study the histopathology and expression of apoptosis in placenta of pregnancy-complicated antiphospholipid syndrome (APS)-positive mouse models. METHOD OF STUDY: ICR mice were immunized with IgG isotype of human anticardiolipin (aCL) and/or lupus anticoagulant (LA). The pathological and apoptotic expression was studied in the placenta of positive APS mice and compared with respective control samples. RESULTS: Mice with passive immunization of human aCL and/or LA produced an increase in fetal resorption along with markedly induced thrombosis in the placenta associated with increased placental apoptosis. In addition, fewer mitotic cells, less trophoblast giant cell invasion, and more shrunken cells in the deciduas were seen. CONCLUSION: Our study showed the pathogenic role of aCL and LA in pregnancy complications.
  American Journal Of Reproductive Immunology 02/2013; · 2.17 Impact Factor
• Article: Osteosclerosis and inhibition of human hematopoiesis in NOG mice expressing human Delta-like 1 in osteoblasts.

  Ryoji Ito, Naoko Negishi, Naoko Irie, Koichi Matsuo, Daisuke Suzuki, Ikumi Katano, Eri Hayakawa, Kenji Kawai, Tsutomu Kamisako, Tomoo Eto, Tomoyuki Ogura, Katsuto Hozumi, Kiyoshi Ando, Sadakazu Aiso, Norikazu Tamaoki, Sonoko Habu, Mamoru Ito
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  ABSTRACT: NOD/Shi-scid IL2rγnull (NOG) mice with severe immunodeficiency are excellent recipients to generate "humanized" mice by the transplantation of human CD34(+) hematopoietic stem cells (HSCs). In this study, we developed NOG mice carrying a human Delta-like1 (DLL1) gene, which is a ligand of the Notch receptor and is known to be important in HSC maintenance and self-renewal. We also analyzed the effect of DLL1 signaling on human hematopoiesis and HSC maintenance using humanized DLL1 transgenic NOG mice. To develop DLL1 transgenic NOG (NOG-D1-Tg) mice, a transgenic vector consisting of a human DLL1 complementary DNA fragment placed downstream of the α1(I) collagen (Col1a1) promoter for expression specifically in osteoblasts was constructed. Human CD34(+) HSCs were transplanted into NOG-D1-Tg mice, and differentiation of lymphoid or myeloid lineage cells from human HSCs and maintenance of HSCs in bone marrow were analyzed. Severe osteosclerosis accompanied by increased bone mass and a decreased number of bone marrow cells were observed in NOG-D1-Tg mice. After human HSC transplantation, development of human B lymphocytes, but not T lymphocytes, was significantly suppressed in both bone marrow and the periphery of NOG-D1-Tg mice. Contrary to the initial expectation, retention of human CD34(+) HSCs was inhibited in the bone marrow of NOG-D1-Tg mice. In conclusion, our data suggest that the development of human B lymphocytes and HSC maintenance in osteosclerotic bone may be suppressed by introducing DLL1. These unique humanized mice with sclerotic bone reconstituted by human HSCs are useful models of hematopoiesis in patients with osteosclerosis, such as osteopetrosis, and for investigation of osteogenesis via Notch signaling.
  Experimental hematology 07/2012; 40(11):953-963.e3. · 3.11 Impact Factor
• Article: A unique preliminary study on placental apoptosis in mice with passive immunization of anti-phosphatidylethanolamine antibodies and anti-factor XII antibodies.

  Shanmugam Velayuthaprabhu, Hidehiko Matsubayashi, Toshitaka Sugi, Masato Nakamura, Yasuyuki Ohnishi, Tomoyuki Ogura, Tatsuhiro Tomiyama, Govindaraju Archunan
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  ABSTRACT: Antiphospholipid antibodies have been investigated both in humans and in animal models. In contrast, there are fewer reports describing anti-phosphatidylethanolamine (aPE) antibodies in humans, and there are no reports of animal studies with aPE till date. Clinically, FXII deficiency or anti-FXII antibodies are sometimes associated with aPE in patients with recurrent pregnancy loss. Therefore, we asked whether aPE and/or anti-FXII in mice could cause fetal resorption, placental thrombosis and apoptosis. Moreover, antibodies to respective target antigens (LDC27 or IPP30) could cause pregnancy failure as well. Animal models were used to carry out these objectives. All the animals were immunized with different antibodies by passive immunization. Placental samples were used for various observations. Mice with passive immunization of aPE (or anti-LDC27) and aFXII (or anti-IPP30) produced a slight increase in fetal resorption, but markedly induced thrombosis and hemorrhage in the placenta associated with lower platelet counts and increased placental apoptosis. In addition, fewer mitotic cells, less trophoblast giant cell invasion, and more shrunken cells in the deciduas were seen. Our study supports the pathogenic role of aPE and aFXII in pregnancy complications and also suggests a beneficial role of LDC27 and IPP30 antigens on pregnancy failures.
  American Journal Of Reproductive Immunology 05/2011; 66(5):373-84. · 2.17 Impact Factor
• Source

  Available from: Masahiro Inoue

  Article: Detection of the onset of ischemia and carcinogenesis by hypoxia-inducible transcription factor-based in vivo bioluminescence imaging.

  Tetsuya Kadonosono, Takahiro Kuchimaru, Shuichi Yamada, Yumi Takahashi, Atsushi Murakami, Taeko Tani, Hitomi Watanabe, Tomoharu Tanaka, Kiichi Hirota, Masahiro Inoue, [......], Takeshi Toyoda, Koji Urano, Kazuhiko Machida, Tomoo Eto, Tomoyuki Ogura, Hideki Tsutsumi, Mamoru Ito, Masahiro Hiraoka, Gen Kondoh, Shinae Kizaka-Kondoh
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  ABSTRACT: An animal model for the early detection of common fatal diseases such as ischemic diseases and cancer is desirable for the development of new drugs and treatment strategies. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates oxygen homeostasis and plays key roles in a number of diseases, including cancer. Here, we established transgenic (Tg) mice that carry HRE/ODD-luciferase (HOL) gene, which generates bioluminescence in an HIF-1-dependent manner and was successfully used in this study to monitor HIF-1 activity in ischemic tissues. To monitor carcinogenesis in vivo, we mated HOL mice with rasH2 Tg mice, which are highly sensitive to carcinogens and are used for short-term carcinogenicity assessments. After rasH2-HOL Tg mice were treated with N-methyl-N-nitrosourea, bioluminescence was detected noninvasively as early as 9 weeks in tissues that contained papillomas and malignant lesions. These results suggest that the Tg mouse lines we established hold significant potential for monitoring the early onset of both ischemia and carcinogenesis and that these lines will be useful for screening chemicals for carcinogenic potential.
  PLoS ONE 01/2011; 6(11):e26640. · 4.09 Impact Factor
• Article: Highly sensitive model for xenogenic GVHD using severe immunodeficient NOG mice.

  Ryoji Ito, Ikumi Katano, Kenji Kawai, Hiroshi Hirata, Tomoyuki Ogura, Tsutomu Kamisako, Tomoo Eto, Mamoru Ito
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  ABSTRACT: Several animal models for xenogenic (xeno) graft versus host disease (GVHD) have been developed in immunodeficient mice, such as C.B-17-scid and nonobese diabetes (NOD)/severe combined immunodeficiency (SCID), by human peripheral blood mononuclear cell (hPBMC) transplantation. However, these models pose problems because they require sublethal total body irradiation of the mice and a large number of hPBMCs to induce GVHD, and the timing of onset of GVHD is also unstable. The aim of this study is to establish improved murine models of xeno-GVHD using novel immunodeficient NOD/Shi-scid IL2r gamma null (NOG) mice. In three strains of immunodeficient mice, NOG, BALB/cA-RAG2 IL2r gamma null, and NOD/SCID mice, GVHD was induced by transplantation of hPBMCs with or without total body irradiation, and the GVHD symptoms in these strains were compared. After intravenous transplantation of hPBMCs, NOG mice showed early onset of GVHD symptoms and a small number of hPBMCs (2.5 x 10(6)) was sufficient to induce GVHD when compared with BALB/cA-RAG2 null IL2r gamma null and NOD/SCID mice. In addition, total body irradiation was not always necessary in the present model. These results indicate that our model using the NOG mouse is a useful tool to investigate GVHD and to develop effective drugs for GVHD.
  Transplantation 07/2009; 87(11):1654-8. · 4.00 Impact Factor
• Article: Establishing EGFP congenic mice in a NOD/Shi-scid IL2Rg(null) (NOG) genetic background using a marker-assisted selection protocol (MASP).

  Hiroshi Suemizu, Chie Yagihashi, Tomoko Mizushima, Tomoyuki Ogura, Tomoo Etoh, Kenji Kawai, Mamoru Ito
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  ABSTRACT: Severely immunocompromised NOD/Shi-scid IL2Rg (null) (NOG) mice, which show higher engraftment efficiency, are useful as recipients in xenotransplantation studies. We generated a NOG-enhanced green fluorescent protein (EGFP) transgenic (Tg) mouse (NOG-EGFP) that was introduced the EGFP transgene from the C57BL/6-EGFP Tg mouse using the speed congenic method with a marker-assisted selection protocol (MASP). With this method, the selection of the male with the closest NOG strain type was repeated four times. When human cord blood CD34(+) cells were transplanted into NOD/Shi-scid, NOG, and NOG-EGFP mice (N(6)), the engraftment efficiency of the NOG-EGFP mice was significantly higher than that of the NOD/Shi- scid mice and was similar to that of the NOG mice. These results suggest that the NOG-EGFP mice, which were generated using the congenic method with MASP, acquired the immunological properties of the NOG mice.
  Experimental Animals 11/2008; 57(5):471-7. · 0.92 Impact Factor
• Article: Interleukin-4-transgenic hu-PBL-SCID mice: a model for the screening of antiviral drugs and immunotherapeutic agents against X4 HIV-1 viruses.

  Kazu Okuma, Reiko Tanaka, Tomoyuki Ogura, Mamoru Ito, Sei Kumakura, Mikiro Yanaka, Masako Nishizawa, Wataru Sugiura, Naoki Yamamoto, Yuetsu Tanaka
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  ABSTRACT: CXCR4-tropic (X4) human immunodeficiency virus type 1 (HIV-1) does not efficiently infect and replicate in severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood mononuclear cells, termed "hu-PBL-SCID mice," due to, at least in part, relatively low levels of expression of the CXCR4 coreceptor. To overcome this limitation, interleukin (IL)-4-transgenic hu-PBL-SCID mice were derived that spontaneously synthesized human IL-4, which has been shown to enhance CXCR4 expression and promote X4 virus infection in vitro. Experiments reported here show that (1) synthesis of human IL-4 in vivo augmented CXCR4 expression on human CD4(+) lymphocytes and importantly led to productive infection of not only X4 HIV-1(NL4-3) but also multidrug-resistant primary clinical isolates and that (2) the in vivo infection could be significantly blocked by the administration of a CXCR4 antagonist. Altogether, IL-4-transgenic hu-PBL-SCID mice provide a useful model for X4 HIV-1 study and testing/screening of anti-X4 viral drugs.
  The Journal of Infectious Diseases 02/2008; 197(1):134-41. · 6.41 Impact Factor
• Article: PCR method for genotyping and zygosity-testing of RasH2 transgenic mice.

  Hiroshi Suemizu, Chika Kito-Maruyama, Yusuke Sotomaru, Tomoyuki Ogura, Kyoji Hioki, Yasuyuki Ohnishi, Norikazu Tamaoki
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  ABSTRACT: In short-term carcinogenicity testing using CB6F1-TgrasH2 mice, sibling nonTgrasH2 mice are used as a negative control. However, selection of TgrasH2 and nonTgrasH2 mice has been performed by PCR with only transgene specific primers by the conventional method. Therefore, the conventional method involves the risk of false negative results due to reaction failure, and contamination with TgrasH2 mice in the control mice group. Based on the nucleotide sequence information around the pre-integration site, we developed a genotyping method for distinguishing not only TgrasH2 mice (hemizygous for the Tg allele) but also nonTgrasH2 (homozygous for the nonTg allele) in a positive manner.
  Experimental Animals 11/2004; 53(5):463-6. · 0.92 Impact Factor