研究者データベース

土佐 紀子(トサ ノリコ)
医学研究院 附属動物実験施設
助教

基本情報

所属

  • 医学研究院 附属動物実験施設

職名

  • 助教

学位

  • 博士(獣医学)(北海道大学)

ホームページURL

J-Global ID

研究分野

  • ライフサイエンス / 実験動物学

担当教育組織

職歴

  • 2009年04月 - 現在 北海道大学 大学院医学研究院附属動物実験施設 助教

研究活動情報

論文

  • Simultaneous serodetection of major rat infectious pathogens by a multiplex immunochromatographic assay.
    Tosa N, Ishida T, Yoshimatsu K, Hayashimoto N, Shiokawa K, Takakura A, and Arikawa J
    Exp. Anim. 70 2 161 - 168 2021年05月 [査読有り][通常論文]
  • Noriko Tosa, Tomoko Ishida, Kumiko Yoshimatsu, Nobuhito Hayashimoto, Kanae Shiokawa, Akira Takakura, Jiro Arikawa
    Journal of the American Association for Laboratory Animal Science : JAALAS 58 6 790 - 795 2019年11月01日 [査読有り]
     
    Serologic monitoring of infectious diseases is important for microbial control in colonies of laboratory mice. Rapid and simple tests that do not require killing animals are valuable for this purpose. In this study, we developed a multiplex immunochromatographic assay (ICA) for detection of antibodies to mouse hepatitis virus (MHV), Sendai virus (also known as hemagglutinating virus of Japan [HVJ]), and Clostridium piliforme (The pathogen that causes Tyzzer disease), which are major infectious diseases in mice. For this assay, an ICA strip was put into a microtube containing 150 μL PBS and either 0.75 μL mouse serum or 1.5 μL whole blood. Binding antibodies were visualized by using protein A-conjugated colloidal gold. Under these conditions, multiplex ICA simultaneously and specifically detected antibodies to multiple antigens. To evaluate the sensitivity and specificity of multiplex ICA, positive serum samples for each infectious disease were used. Sensitivities of the multiplex ICA test for MHV, HVJ, and C. piliforme were 100%, 100%, and 90%, respectively. No nonspecific reaction was observed in any of the 30 positive sera. In addition, 10 samples of uninfected sera did not show any bands except for the control line. These observations indicate high specificity of the multiplex ICA test. Moreover, the multiplex ICA could be applied to diluted blood. These results indicate that the multiplex ICA is appropriate for rapid, simple, and safe serologic testing of laboratory mice.
  • Noriko Tosa, Kumiko Yoshimatsu, Motoko Takahashi, Jiro Arikawa
    Biomedical Research 40 1 9 - 15 2019年 [査読有り][通常論文]
     
    Can f 1 belongs to the lipocalin superfamily and is considered to be an animal allergen. The immune response induced by Can f 1 in mice was compared with that induced by ovalbumin (OVA), a typical food allergen. Female BALB/c and C57BL/6 mice (6 weeks of age) were subcutaneously injected with Can f 1 or OVA with or without aluminum hydroxide (Alum) three times with intervals of two weeks. Serum levels of total IgE or antigen-specific IgE and production of IL13 and IFNγ from splenocytes were analyzed. Immunization with Can f 1 or OVA increased serum levels of both total IgE and antigen-specific IgE significantly irrespective of Alum. These results indicate that Can f 1 and OVA were able to induce allergic sensitization in mice. Splenocyte production of IL13 in mice immunized with Can f 1 or OVA with and without Alum were significantly increased after stimulation with each antigen. However, IL13 levels in the mice immunized with Can f 1 with Alum were significantly lower than those immunized without Alum. Increases in IFNγ levels after stimulation with Can f 1 or OVA were not remarkable. No influence of genetic backgrounds of BALB/c and C57BL/6 mice was found. Although Can f 1 induced Th2 type immune responses as was also the case for immunization with OVA, an inhibitory effect of Alum on induction of IL13 was observed only in mice immunized with Can f 1. These results suggest that the immune mechanism for allergic sensitization with Can f 1 is different from that with OVA.
  • Variation in the bacterial conditions inside cages is correlated with intracage humidity and ammonia levels.
    Tosa N, Yoshimatsu K, Tadasuke Tsukiyama, Hatakeyama S, Arikawa J
    Lab Animal and Environ 21 2 87 - 98 2013年 [査読有り][通常論文]
  • TOSA Noriko, YOSHIMATSU Kumiko, ARIKAWA Jiro
    Lab Animal and Environ 20 1 1 - 8 2012年 [査読有り][通常論文]
  • Effect of environmental enrichment after the occurrence of wet bedding created by mice and abnormal fur in mice.
    Tosa N, Yoshimatsu K, Arikawa J
    J Am Assoc Lab Anim Sci 50 5 779 - 780 2011年09月 [査読有り][通常論文]
  • Tokimasa Hida, Hitoshi Sohma, Yasuo Kokai, Akinori Kawakami, Kuninori Hirosaki, Masae Okura, Noriko Tosa, Toshiharu Yamashita, Kowichi Jimbow
    JOURNAL OF DERMATOLOGY 38 5 432 - 441 2011年05月 [査読有り][通常論文]
     
    How melanosomal proteins such as enzymic proteins (tyrosinase and tyrosinase-related proteins, Tyrps) and structural protein (gp100) are transported from Golgi to melanosomal compartments is not yet fully understood. A number of small GTPases have been found to be associated with melanosomes and we have identified one of them, Rab7, a regulator of vesicular transport, organelle motility, phospholipid signaling and cytosolic degradative machinery, as being involved in the transport of Tyrp1 from Golgi to stage I melanosomes. This study further characterizes the role of Rab7 as a regulator of differential sorting of melanosomal proteins in this process. Murine melanocytes were transiently transfected with a plasmid encoding either wild-type (Rab7WT), constitutively active (Rab7Q67L) or dominant-negative (Rab7N125I and Rab7T22N) Rab7. Through immunocytostaining and confocal laser scanning microscopy, we quantitatively compared the bio-distribution of melanosomal proteins between Rab7WT-expressing cells and mutant Rab7-expressing cells. We also characterized their differential elimination from melanosomal compartments by Rab7 by utilizing a proteasome inhibitor, MG132. Our findings indicate that Rab7 plays an important role in differential sorting of tyrosinase, Tyrp1 and gp100 in early melanogenesis cascade, and that it is more specifically involved with Tyrp1 than tyrosinase and gp100 in the trafficking from Golgi to melanosomes and the specific exit from the degradative process.
  • Noriko Tosa, Atsushi Iwai, Taku Tanaka, Tomoka Kumagai, Takeshi Nitta, Satoko Chiba, Masahiro Maeda, Yousuke Takahama, Toshimitsu Uede, Tadaaki Miyazaki
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 395 3 356 - 360 2010年05月 [査読有り][通常論文]
     
    Death-associated protein 3 (DAP3) is crucial for promoting apoptosis induced by various stimulations. This report demonstrates that DAP3 is also important for T cell receptor (TCR)-mediated apoptosis induction in immature thymocytes. Enforced expression of DAP3 accelerated the negative selection in developing thymocytes, using the reaggregate thymus organ culture system. In addition, expression of DAP3 accelerated TCR-mediated apoptosis induction in DO11.10 cells. We also demonstrated that DAP3 translocates into the nucleus during TCR-mediated apoptosis in a Nur77 dependent manner. It is concluded that DAP3 is critical for TCR-mediated induction of apoptosis at the downstream of Nur77. (C) 2010 Elsevier Inc. All rights reserved.
  • T Miyazaki, M Shen, D Fujikura, N Tosa, HR Kim, S Kon, T Uede, JC Reed
    JOURNAL OF BIOLOGICAL CHEMISTRY 279 43 44667 - 44672 2004年10月 [査読有り][通常論文]
     
    Detachment of adherent epithelial cells from the extracellular matrix induces apoptosis, known as anoikis. Integrin stimulation protects cells from anoikis, but the responsible mechanisms are not well known. Here, we demonstrated that a pro-apoptotic GTP-binding protein, DAP3 (death-associated protein 3), is critical for induction of anoikis. Down-regulation of DAP3 expression by antisense oligonucleotides inhibited anoikis. Conversely, overexpression of DAP3 augmented cell death and caspase activation induced by cell detachment. Furthermore, the association of DAP3 with FADD and the activation of caspase-8 were induced by cell detachment. We also showed that DAP3 is phosphorylated by kinase Akt (PKB), and active Akt can nullify apoptosis induction by DAP3. Mutation of a consensus Akt phosphorylation site in DAP3 renders it resistant to suppression by active Akt in cells. Integrin ligation stimulates Akt activation and phosphorylation of DAP3 in intact cells, as well as suppresses the ability of DAP3 overexpression to augment anoikis. Involvement of DAP3 in anoikis signaling demonstrates a novel role for this GTP-binding protein in apoptosis induction caused by cell detachment.
  • Miyazaki F, Shen M, Tosa N, Fujikura D, Kon S, Uede T, Reed JC
    FASEB JOURNAL 18 4 A42  2004年03月23日 [査読有り][通常論文]
  • N Tosa, M Murakami, WY Jia, M Yokoyama, T Masunaga, C Iwabuchi, M Inobe, K Iwabuchi, T Miyazaki, K Onoe, M Iwata, T Uede
    INTERNATIONAL IMMUNOLOGY 15 6 741 - 749 2003年06月 [査読有り][通常論文]
     
    Transcriptional expression of a gene or genes is absolutely required for induction of glucocorticold-induced thymocyte apoptosis. We have previously shown that expression of T cell death-associated gene 8 (TDAG8) is quickly induced exclusively in the thymus after dexamethasone (DEX) treatment. Here, we present data that TDAG8 expression is induced prior to induction of DEX-mediated apoptosis. In contrast, TDAG8 expression in thymocytes was not induced in the process of gamma-irradiation-mediated apoptosis. TDAG8 expression accelerated only DEX-induced, but not TCR-mediated or gamma-irradiation-induced, thymocyte apoptosis in transgenic mice overexpressing TDAG8. Interestingly, these effects were specifically detected in CD4(+)CD8(+) double-positive thymocytes. Moreover, activation of caspase-3, -8 and -9 was enhanced in thymocytes of TDAG8 transgenic mice after DEX stimulation. In conclusion, TDAG8 expression is involved in glucocorticold-induced signals to activate caspase-9, -8 and -3 for subsequent apoptosis induction in CD4(+)CD8(+) double-positive thymocytes.
  • Iwabuchi K, Iwabuchi C, Tone S, Itoh D, Tosa N, Negishi I, Ogasawara K, Uede T, Onoe K
    Blood 91 6 1765 - 1775 2001年 [査読有り][通常論文]
  • M Takiguchi, M Murakami, Nakagawa, I, MM Rashid, N Tosa, S Chikuma, A Hashimoto, T Uede
    JOURNAL OF VETERINARY MEDICAL SCIENCE 62 1 29 - 36 2000年01月 [査読有り][通常論文]
     
    MRL/lpr mouse is an established animal model which develops autoimmune diseases including glomerulonephritis, sialoadenitis, hepatitis and inflammatory lung disease. Additionally, it has been reported that lpr strains uniquely accumulate CD3(+)CD4(-)CD8(-)B220(+) (double negative, DN) T cells in lymphoid organs leading to lymphadenopathy and splenomegaly. To investigate the role of CD28/CTLA4-B7 pathway in the development of lymphadenopathy and splenomegaly, MRL/lpr mice were treated with soluble form of CTLA4 molecules. CTLA4IgG, which efficiently blocks this pathway. It was demonstrated that (i) the development of DN T cells was independent of the CD28/CTLA4-B7 pathway, (ii) the CD28/CTLA4-B7 pathway was required for the development of lymphadenopathy and splenomegaly, (iii) the CD28/CTLA4-B7 pathway was important for the accumulation of various cell populations in the lymph node and spleen, (iv) composition of the accumulating cell populations was not altered by CTLA4IgG treatment, and (v) activation of conventional T cells and IL-4 production from conventional T cells were the CD28/CTLA4-B7 pathway dependent. Thus, we concluded that the CD28/CTLA4-B7 pathway was required for the development of full-blown lymphadenopathy and splenomegaly in MRL/lpr mice.
  • H Hotta, S Kon, YU Katagiri, N Tosa, T Tsukamoto, AF Chambers, T Uede
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 257 1 6 - 11 1999年04月 [査読有り][通常論文]
     
    We immunized rats with recombinant murine osteopontin protein and obtained four monoclonal antibodies recognizing distinct epitopes of murine osteopontin. OPN1.2 recognized the amino-terminal half of OPN, while OPN2.2, OPN2.3, and OPN3.1 recognized the carboxy-terminal half of OPN. The epitope recognized by OPN2.2 was destroyed by further cleavage of the carboxy half of OPN. The epitope recognized by OPN2.3 was located in the amino-terminal end of the carboxy half of OPN, whereas that recognized by OPN3.1 was located in the carboxy-terminal end of the carboxy half of OPN. OPN1.2 and OPN2.2 recognized thrombin-cleaved osteopontin, whereas thrombin-cleaved osteopontin was not recognized by OPN2.3 and OPN3.1. Thus, these monoclonal antibodies will be useful in structure/function studies of the role of osteopontin in murine models of disease. (C) 1999 Academic Press.
  • K Mominoki, N Nakagawa-Tosa, M Morimatsu, B Syuto, M Saito
    Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 110 4 785 - 9 1995年04月 
    Haptoglobin (Hp), a hemoglobin-binding protein in plasma, consists of alpha and beta subunits and has a tetra-chain arrangement (beta-alpha-alpha-beta) connected by disulfide bridges in most mammals so far examined. Dog Hp has been reported to be unique compared with other Hps in respect that (1) the two alpha beta units are joined by a non-covalent interaction rather than a disulfide bridge and (2) the alpha chain has an oligosaccharide-binding sequence (Asn-X-Ser/Thr) and is glycosylated. To determine whether the unique structures of dog Hp are common in the Carnivora, we purified Hps from sera of bear and cat, and analyzed their subunit structure and partial amino acid sequences. The analyses by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, under both reducing and non-reducing conditions, revealed that bear and cat Hps have similar subunit arrangements to dog Hp, suggesting the absence of a disulfide bridge between two alpha chains. This was confirmed by amino acid sequence analysis of the alpha chains: that is, Cys15 participating in the inter-alpha chain disulfide bridge was replaced by Val in bear or Leu in cat and dog. Thus, the unique subunit arrangement of Hp reported in dog may be common in the Carnivora. In contrast to dog Hp, however, alpha chains of bear and cat Hps were found not to have the typical oligosaccharide binding sequence on their alpha chains and were not glycosylated.
  • K MOMINOKI, N NAKAGAWATOSA, M MORIMATSU, B SYUTO, M SAITO
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY 110 4 785 - 789 1995年04月 [査読有り][通常論文]
     
    Haptoglobin (Hp), a hemoglobin-binding protein in plasma, consists of alpha and beta subunits and has a tetra-chain arrangement (beta-alpha-alpha-beta) connected by disulfide bridges in most mammals so far examined, Dog Hp has been reported to be unique compared with other Hps in respect that (1) the two alpha beta units are joined by a non-covalent interaction rather than a disulfide bridge and (2) the alpha chain has an oligosaccharide-binding sequence (Asn-X-Ser/Thr) and is glycosylated, To determine whether the unique structures of dog Hp are common in the Carnivora, we purified Hps from sera of bear and cat, and analyzed their subunit structure and partial amino acid sequences, The analyses by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, under both reducing and non-reducing conditions, revealed that bear and cat Hps have similar subunit arrangements to dog Hp, suggesting the absence of a disulfide bridge between two a chains, This was confirmed by amino acid sequence analysis of the alpha chains: that is, Cys(15) participating in the inter-a chain disulfide bridge was replaced by Val in bear or Leu in cat and dog, Thus, the unique subunit arrangement of Hp reported in dog may be common in the Carnivora, In contrast to dog Hp, however, alpha chains of bear and cat Hps were found not to have the typical oligosaccharide binding sequence on their alpha chains and were not glycosylated.
  • N NAKAGAWATOSA, M MORIMATSU, M KAWASAKI, H NAKATSUJI, B SYUTO, M SAITO
    JOURNAL OF VETERINARY MEDICAL SCIENCE 57 2 219 - 223 1995年04月 [査読有り][通常論文]
     
    The hepatic synthesis of acute phase proteins in ruminants has been suggested to be regulated by some mechanisms different from those in other species such as rodents and human. To explore possible regulatory factors unique to ruminants, we examined effects of interleukin (IL)-6, IL-1 and tumor necrosis factor (TNF), on haptoglobin (Hp) synthesis using a primary culture system of bovine hepatocytes. After bovine primary cultured hepatocytes were incubated in the presence of various concentrations of the cytokines, the synthesis and mRNA level of haptoglobin and albumin were measured by labeling with [S-35]-methionine and immunoprecipitation, and by Northern blot analysis, respectively. Hp synthesis was dose-dependently increased by recombinant human (rh) IL-6, and also by rhTNF-alpha, but to a less extent, while it was not affected by rhlL-1 beta. The stimulatory effect is mainly pretranslational, because mRNA level of Hp changed in parallel with protein synthesis. In contrast, albumin synthesis was suppressed by these three cytokines similarly. These results are inconsistent with the previously proposed view that TNF and IL-l overlap in their pathways leading to the transcriptional activation of many acute phase protein genes. In conclusion, there is a species-specific unique signaling system, especially for TNF, in transcriptional activation of bovine Hp gene.
  • N NAKAGAWATOSA, M MORIMATSU, K MOMINOKI, H NAKATSUJI, B SYUTO, M SAITO
    JOURNAL OF VETERINARY MEDICAL SCIENCE 56 1 125 - 129 1994年02月 [査読有り][通常論文]
     
    We describe a technique for isolation and primary culture of bovine hepatocytes, and their metabolic characterization. Hepatocytes were isolated from the caudate lobe of bovine liver by perfusion with 0.25 mM ethyleneglycol tetraacetic acid and 0.05% collagenase. The viability and yield of the cells were 70-92% and 0.1-3.6 x 10(7) cells/g liver, respectively. When the isolated hepatocytes were cultured in Williams' medium E, they began to spread in 3 hr and formed monolayers in 24 hr. These monolayers were retained for at least 6 days. To monitor the metabolic activities specific to liver, synthesis and secretion of albumin were measured by labeling with [S-35]-methionine and immunoprecipitation. This activity was low in isolated hepatocytes, but increased after culturing 1-3 days, and decreased again after 6 days. Glycogenolytic activity was also assessed by measuring glucose release to the medium by stimulation with epinephrine. The glycogenolytic response to epinephrine was also enhanced by culturing the hepatocytes 1-3 days, but was decreased after 6 days. Since the isolated bovine hepatocytes retained the liver-specific activities of albumin synthesis and glycogenolysis for several days in culture, these cells are useful for cellular and molecular studies on the functions of bovine liver.
  • N TOSA, M MORIMATSU, M NAKAGAWA, F MIYOSHI, E UCHIDA, M NIIYAMA, B SYUTO, M SAITO
    JOURNAL OF VETERINARY MEDICAL SCIENCE 55 1 27 - 31 1993年02月 [査読有り][通常論文]
     
    Polyacrylamide gel electrophoretic analysis of canine serum protein has revealed that the administration of anthelmintics elicits an increase in a certain serum protein. This protein, named PT60, was partially purified by ammonium sulfate fractionation and preparative electrophoresis. The purified PT60 gave a single band with the molecular size of 53 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under non-reducing conditions. After reduction with 2-mercaptoethanol, two bands appeared at 35 kDa and 17 kDa, indicating that PT60 consists of two subunits which are linked with each other by disulfide bonds. PT60 had the capacity to bind to hemoglobin. In an immunodiffusion test, an antiserum against PT60 cross-reacted with canine haptoglobin (Hp). N-terminal amino acid sequences of two PT60 subunits were identical to those of alpha and beta subunits of canine Hp, respectively. Thus, PT60 was identified as Hp.

その他活動・業績

受賞

  • 2023年09月 Asian Federation of Laboratory Animal Science Assosiations 第9回 AFLAS Congress 2023 トラベルアワード
     Analysis of storage and transport conditions of multiplex ICG sticks for diagnosis of infectious diseases in rats and mice 
    受賞者: Noriko Tosa
  • 2013年05月 日本実験動物技術者協会 第4回実験動物福祉奨励賞
     マウスの被毛異常または床敷湿潤が発生した後の環境エンリッチメントの効果 
    受賞者: 土佐 紀子

教育活動情報

主要な担当授業

  • 医理工学研究概論
    開講年度 : 2021年
    課程区分 : 修士課程
    開講学部 : 医理工学院
    キーワード : 動物実験、図書館、電子ジャーナル、共同利用施設、RI実験
  • 基本医学研究概論
    開講年度 : 2021年
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 動物実験、図書館、電子ジャーナル、共同利用施設、RI実験
  • 医学研究概論
    開講年度 : 2021年
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 動物実験、図書館、電子ジャーナル、共同利用施設、RI実験
  • 微生物・免疫学実習
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 医学部
    キーワード : 細菌、ウイルス、無菌操作、グラム染色、抗酸菌染色、培養、細胞培養、定量、抗生物質、CPE、PCR、ELISA、IFA、蛍光抗体法、抗体、ブロッティング、炎症性サイトカイン、フローサイトメトリー、リンパ球、マクロファージ


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