2024/04/23 更新

写真a

トミヤマ チカコ
富山 智香子
TOMIYAMA Chikako
所属
教育研究院 医歯学系 保健学系列 教授
保健学研究科 保健学専攻 教授
医学部 保健学科 検査技術科学専攻 教授
職名
教授
外部リンク

学位

  • 博士(医学) ( 2006年3月   新潟大学 )

研究キーワード

  • 肝臓

  • 樹状細胞

  • 脂質代謝

  • エストロゲン

  • 自己免疫疾患

  • mild hyperthermia

研究分野

  • ライフサイエンス / 免疫学

  • その他 / その他  / 病態検査学

経歴(researchmap)

  • 新潟大学   医学部 保健学科   准教授

    2010年10月 - 現在

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  • 新潟大学   保健学研究科 保健学専攻   准教授

    2010年10月 - 現在

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  • 新潟大学   教育研究院 医歯学系 保健学系列   准教授

    2010年10月 - 現在

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  • 新潟大学   医学部 保健学科   助教

    2008年4月 - 2010年9月

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  • 新潟大学   医学部   職員(教務系)

    2002年4月 - 2008年3月

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経歴

  • 新潟大学   保健学研究科 保健学専攻   教授

    2024年4月 - 現在

  • 新潟大学   教育研究院 医歯学系 保健学系列   教授

    2024年4月 - 現在

  • 新潟大学   医学部 保健学科 検査技術科学専攻   教授

    2024年4月 - 現在

  • 新潟大学   医学部   教授

    2024年4月 - 現在

  • 新潟大学   保健学研究科 保健学専攻   准教授

    2010年10月 - 2024年3月

  • 新潟大学   医学部 保健学科   准教授

    2010年10月 - 2024年3月

  • 新潟大学   保健学研究科 保健学専攻   准教授

    2010年10月 - 2024年3月

  • 新潟大学   医学部 保健学科   助教

    2008年4月 - 2010年9月

  • 新潟大学   職員(教務系)

    2002年4月 - 2008年3月

▶ 全件表示

学歴

  • 新潟大学   医歯学総合研究科   地域疾病制御医学専攻

    - 2006年3月

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    国名: 日本国

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所属学協会

  • 日本免疫学会

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  • 日本リンパ網内系学会

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  • マクロファージ分子細胞生物学研究会

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取得資格

  • 臨床検査技師

 

論文

  • Involvement of Dectin-2 in the innate inflammatory response triggered by influenza virus hemagglutinin 査読

    Hideki Yamamoto, Chikako Tomiyama, Sho Yamasaki, Shinobu Saijo, Yoichiro Iwakura, Kazuyoshi Kawakami

    Advances in Infectious Diseases   13 ( 3 )   478 - 497   2023年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.4236/aid.2023.133039

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  • Mental status is significantly associated with low back pain: a survey-based cross-sectional study among Japanese women

    Mayumi Watanabe, Chikako Tomiyama, Takuya Nikaido, Tokimasa Takeda, Nozomu Mandai

    BMC Research Notes   16 ( 1 )   2023年1月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Abstract

    Objective

    Low back pain (LBP) is a highly prevalent condition that poses significant patient burden. This cross-sectional study identified factors associated with LBP occurrence and developed a strategy to identify, prevent, and reduce LBP-related burden on patient health. A web-based questionnaire-answering system was used to assess the potential effects of LBP on mental health, assessing five domains (physical features, demographics, lifestyle, diet, and mental status) conceptually associated with hie, a common disease state traditionally described in the Japanese culture as a chilly sensation.

    Results

    Of 1000 women, 354 had and 646 did not have LBP. The Chi test identified 21 factors, and subsequent multivariate logistic regression indicated eight factors significantly associated with LBP: age, history of physician consultation regarding anemia, history of analgesic agents, dietary limitations, nocturia, sauna use, hie, and fatigue. Furthermore, women with LBP exhibited a significantly lower body temperature (BT) in the axilla/on the forehead than women without LBP. LBP and hie are subjective and potentially affected by patient mental status. Stress reduces blood circulation, causing hypothermia and possibly worsening LBP. Therefore, mental-health support is important for patients with LBP to reduce physiological stress. Hyperthermia therapy, a traditionally prescribed intervention, is a potential intervention for future studies.

    DOI: 10.1186/s13104-023-06276-4

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    その他リンク: https://link.springer.com/article/10.1186/s13104-023-06276-4/fulltext.html

  • A Study of <i>Hie</i> and LBP: The First Step to Improve Subjective Well-Being

    Mayumi Watanabe, Chikako Tomiyama, Takuya Nikaido, Masae Ryufuku, Nozom Mandai, Tokimasa Takeda, Tsutomu Komine

    Health   15 ( 10 )   1013 - 1023   2023年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Research Publishing, Inc.  

    DOI: 10.4236/health.2023.1510069

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  • Factors associated with hie (chilly sensation): an analysis among Japanese women

    Mayumi Watanabe, Chikako Tomiyama, Takuya Nikaido, Tokimasa Takeda, Nozomu Mandai

    European Journal of Integrative Medicine   102211 - 102211   2022年11月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.eujim.2022.102211

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  • Blood Pressure Balance as a Marker for Early Detection of Cerebral Infarction and a Criterion for Inclusion/Exclusion from Acupuncture Treatment 査読

    Mayumi Watanabe, Yoshinobu Nakamura, Chikako Tomiyama, Nozomu Mandai, Hanaa Yousef Bakir, Tokimasa Takeda

    Health   13 ( 08 )   857 - 867   2021年8月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Research Publishing, Inc.  

    DOI: 10.4236/health.2021.138066

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  • Dectin-2-mediated initiation of immune responses caused by influenza virus hemagglutinin 査読

    Hideki Yamamoto, Chikako Tomiyama, Ko Sato, Jun Kasamatsu, Kazuki Takano, Aya Umeki, Nana Nakahata, Tomomitsu Miyasaka, Emi Kanno, Hiromasa Tanno, Sho Yamasaki, Shinobu Saijo, Yoichiro Iwakura, Keiko Ishii, Kazuyoshi Kawakami

    BIOMEDICAL RESEARCH-TOKYO   42 ( 2 )   53 - +   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMEDICAL RESEARCH PRESS LTD  

    Antigen-presenting cells express pattern recognition receptors (PRRs), which sense pathogen-associated molecular patterns from microorganisms and lead to the induction of inflammatory responses. C-type lectin receptors (CLRs), the representative PRRs, bind to microbial polysaccharides, among which Dectin-2 and Mincle recognize mannose-containing polysaccharides. Because influenza virus (IFV) hemagglutinin (HA) is rich in mannose polysaccharides, Dectin-2 or Mincle may contribute to the recognition of HA. In this study, we addressed the possible involvement of Dectin-2 and Mincle in the viral recognition and the initiation of cytokine production. Interleukin (IL)-12p40 and IL-6 production by bone marrow-derived dendritic cells (BM-DCs) upon stimulation with HA was significantly reduced in Dectin-2 knockout (KO) mice compared to wild-type (WT) mice whereas there was no difference between WT mice and Mincle KO mice. BM-DCs that were treated with Syk inhibitor resulted in a significant reduction of cytokine production upon stimulation with HA. The treatment of BM-DCs with methyl-alpha-D-mannopyranoside (ManP) also led to a significant reduction in cytokine production by BM-DCs that were stimulated with HA, except for the A/H1N1pdm09 subtype. IL-12p40 and IL-6 synthesis by BM-DCs was completely diminished upon stimulation with HA treated with concanavalin A (ConA)-bound sepharose beads. Finally, GFP expression was detected in reporter cells that were transfected with the Dectin-2 gene, but not with the Mincle gene, when stimulated with HA derived from the A/H3N2 subtype. These data suggested that Dectin-2 may be a key molecule as the sensor for IFV to initiate the immune response and regulate the pathogenesis of IFV infection.

    DOI: 10.2220/biomedres.42.53

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  • Emotional Effects on Factors Associated with Chronic Low Back Pain 査読

    Koichi Ouchi, Mayumi Watanabe, Chikako Tomiyama, Takuya Nikaido, Zaigen Oh, Toru Hirano, Kohei Akazawa, Nozomu Mandai

    JOURNAL OF PAIN RESEARCH   12   3343 - 3353   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:DOVE MEDICAL PRESS LTD  

    Purpose: Although chronic low back pain (CLBP) has profound effects on patients, society, and economy, its causes are difficult to identify. Psychogenic effects or social stress is known to affect CLBP; hence, investigation of its underlying causes requires a multifactorial approach. We determined the factors associated with CLBP by using an Internet-based survey. To prevent CLBP, we need to understand its cause and background.Patients and methods: A total of 1000 participants either with (+) or without (-) CLBP answered the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), which assesses five domains of CLBP: low back pain, lumbar function, walking ability, social life function and mental health. We also administered a new questionnaire for participants, that comprised five different domains: Body, Lifestyle, Emotion, Diet, and Social. To evaluate psychogenic effects on CLBP, we added two original factors, namely outshout and HIE, which have not yet been studied. HIE is a traditional concept (sense) of "feeling cold" or "chilly." All participants completed both questionnaires.Results: Multivariate logistic regression analysis extracted four factors (sleep, room temperature, outshout, and HIE) that were associated with CLBP. The mental health domain was assessed using the JOABPEQ for each of these factors. The factors outshout and HIE differed between CLBP (+) and CLBP (-) patients. CLBP (-) participants also showed a difference in Sleep and HIE factors.Conclusion: Among psychogenic effects, Emotion was common to all the four extracted factors. There was no common physical divisor. Therefore, we hypothesized that acute low back pain might develop into CLBP in the presence of psychological stress or other emotional factors such as outshout or HIE. Hence, we need to consider both physical and psychogenic effects in the prevention and treatment of CLBP. Furthermore, appropriate evaluation and treatment of psychological stress may be effective in reducing CLBP.

    DOI: 10.2147/JPR.S223190

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  • Effects of Mild Hyperthermia Treatment Using Nano-Mist Sauna on Blood Gas Parameters and Skin Appearance 査読

    Takayoshi Hayakawa, Mayumi Watanabe, Chikako Tomiyama, Ayaka Sasagawa, Takashi Honma, Akihiro Inada, Toru Abo

    Health   10 ( 05 )   577 - 586   2018年5月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Research Publishing, Inc.  

    DOI: 10.4236/health.2018.105046

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    その他リンク: http://file.scirp.org/xml/84784.xml

  • Sleep and Stress of Late Middle Age Males Who Are Forced to Live in Emergency Temporary Houses and Post-Earthquake Public Houses for a Long Period Due to the Fukushima Daiichi Nuclear Power Station Accident 査読

    Yuka Iwasa, Yoshiyuki Muramatsu, Hagiko Aoki, Chikako Tomiyama, Tomoko Saito, Mayumi Nishikata, Mieko Uchiyama

    Health   09 ( 13 )   1787 - 1800   2017年12月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Research Publishing, Inc.  

    DOI: 10.4236/health.2017.913130

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  • Characteristic Changes Defined via Comparison of the Big-Five Personalities in Japanese University Freshmen from Years 2000 to 2016 査読

    Kayo Shichiri, Akira Tachibana, Hiroko Abe, Takuro Kunizuka, Yuri Yoshida, Chikako Tomiyama, Mayumi Watanabe

    Health   09 ( 10 )   1348 - 1354   2017年9月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Research Publishing, Inc.  

    DOI: 10.4236/health.2017.910098

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  • A Specific Pattern in the Basal Body Temperature Chart during the First Week of Pregnancy May Warn of a Miscarriage Crisis 査読

    Mayumi Watanabe, Yoshinobu Nakamura, Chikako Tomiyama, Toru Abo

    Health   8 ( 8 )   723 - 729   2016年5月

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  • Repetitive manual acupuncture increases markers of innate immunity in mice subjected to restraint stress 査読

    Mayumi Watanabe, Eisuke Kainuma, Chikako Tomiyama

    ACUPUNCTURE IN MEDICINE   33 ( 4 )   312 - 318   2015年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BMJ PUBLISHING GROUP  

    Objective To study the effects of repetitive manual acupuncture treatment on acute stress in mice and to explore its impact on the immune system.
    Methods Thirty-six mice were randomly allocated to one of four groups: control, acupuncture, stress and acupuncture+stress (n=9 each). Mice in the two acupuncture groups were given daily acupuncture treatment superficially (to skin depth) at CV6, CV12 and bilateral ST25, LR14, GB20, GB21, BL10, BL11, BL13, BL14, BL19, BL23 and BL25 for 7 days. On the eighth day mice in the stress and acupuncture+stress groups were exposed to acute stress for 2 h by confinement in a 50 mL centrifuge tube. Body temperature, blood glucose, the number and subpopulation ratios of leucocytes in the liver, spleen and thymus, natural killer (NK) cell percentage cytotoxicity and serum corticosterone and interferon gamma IFN gamma were quantified.
    Results Mice exposed to stress (irrespective of acupuncture treatment) exhibited hypothermia and hyperglycaemia. However, the increase in glucose level was mitigated by repetitive acupuncture treatment (p<0.05). Percentage cytotoxicity and the level of corticosterone were significantly increased after stress but were unaffected by acupuncture. IFN gamma levels did not differ between the groups. Hepatic innate immunity in the liver appeared to be stimulated by repetitive acupuncture treatment as proportions of extrathymic T cells, NK cells and NKT cells in the liver were greatest in the acupuncture+stress group and significantly increased relative to the control group.
    Conclusions Repetitive manual acupuncture mitigated stress-induced hyperglycaemia and enhanced markers of innate immunity in the liver within the range of normal homoeostasis. As long as acupuncture stimuli were appropriately applied, they did not appear to be stressful to the mice.

    DOI: 10.1136/acupmed-2014-010660

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  • Does East Meet West?—The Association between Oriental Tongue Inspection and Western Clinical Assays of White Blood Cell Subsets 査読

    Mayumi Watanabe, Eisuke Kainuma, Chikako Tomiyama, Zaigen Oh, Joe Koshizawa, Gouzou Nagano

    Health   07 ( 07 )   801 - 808   2015年7月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Research Publishing, Inc.  

    DOI: 10.4236/health.2015.77094

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    その他リンク: http://file.scirp.org/xml/57742.xml

  • A Questionnaire Survey in Kidney Transplant Outpatients: Factors Associated with Good Self-Management 査読

    Minako Shimaya, Mayumi Watanabe, Motoi Azumi, Kayo Shichiri, Chikako Tomiyama, Mayumi Tanabe, Sachi Sato, Kouhei Akazawa

    Health   07 ( 05 )   589 - 595   2015年5月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Research Publishing, Inc.  

    DOI: 10.4236/health.2015.75070

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    その他リンク: http://file.scirp.org/xml/56482.xml

  • The effect of repetitive mild hyperthermia on body temperature, the autonomic nervous system, and innate and adaptive immunity 査読

    Chikako Tomiyama, Mayumi Watanabe, Takashi Honma, Akihiro Inada, Takayoshi Hayakawa, Masae Ryutuku, Toru Abo

    BIOMEDICAL RESEARCH-TOKYO   36 ( 2 )   135 - 142   2015年4月

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    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:BIOMEDICAL RESEARCH PRESS LTD  

    The effect of repetitive mild hyperthermia on body temperature, the autonomic nervous system, and innate and adaptive immunity was investigated using a new hyperthermia treatment system, nanomist sauna (NMS). Six healthy volunteers participated and the concentration of catecholamines and cortisol, and the frequency and function of leukocytes in the peripheral blood were investigated before and after successive 7 days of hyperthermia treatment (20 min/day, 40 degrees C, 100% relative humidity). After treatment, the blood level of adrenaline and cortisol on the 7th day was decreased compared with the 1st day, indicating the suppression of the sympathetic nervous system activity. Moreover, the frequency of CD56(+)NK, CD56(+)NKT and B cells on the 7th day tended to be increased compared with the 1st day. The frequency of HLA-DR-positive NK and NKT cells and expression of HLA-DR on B and T cells increased. The cytotoxicity of NK cells and proliferative response of B cells were also elevated. The results indicate that repetitive mild hyperthermia treatment might suppress excessive sympathetic dominance and modify immunity. Additionally, because it can provide the same effects as conventional hyperthermia treatments with minimal burden to the body, NMS may be a novel patient- and elderly-friendly hyperthermia treatment for health promotion.

    DOI: 10.2220/biomedres.36.135

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  • On/off switching of capillary vessel flow controls mitochondrial and glycolysis pathways for energy production 査読

    Toru Abo, Mayumi Watanabe, Chikako Tomiyama, Yasuhiro Kanda

    MEDICAL HYPOTHESES   83 ( 1 )   99 - 100   2014年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CHURCHILL LIVINGSTONE  

    Capillary vessel flow in the base of the fingernail can be observed by microscopy. This flow is switched off under some conditions, such as coldness, surprise, and anger and is switched on again under other conditions, such as warming, relaxation, and mild exercise. In other words, capillary vessels perform two functions: switching flow on and off. It is speculated that the switch-off function is necessary to direct energy production to the glycolysis pathway, while the switch-on function is necessary for the mitochondrial pathway. This is because glycolysis takes place under anaerobic conditions, while oxidative phosphorylation in the mitochondria proceeds under aerobic conditions in the body. To switch off circulation, the negative electric charges on the surface of erythrocytes and the capillary wall may be decreased by stimulation of the sympathetic nerves and secretion of steroid hormones. Negative charge usually acts as repulsive force between erythrocytes and between erythrocytes and the capillary wall. By decreasing the negative charge, erythrocytes can aggregate and also adhere to the capillary wall. These behaviors may be related to the capillary flow switch-off function. Here, it is emphasized that the capillary vessels possess not only a switch-on function but also a switch-off function for circulation. (C) 2014 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.mehy.2014.03.035

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  • Increased activated natural killer T cells in the liver of patients with advancedstage primary biliary cirrhosis 査読

    ASO-ISHIMOTO Yuiko, YAMAGIWA Satoshi, ICHIDA Takafumi, MIYAKAWA Ryoko, TOMIYAMA Chikako, SATO Yoshinobu, WATANABE Hisami, AOYAGI Yutaka

    Biomedical Research   35 ( 2 )   161 - 169   2014年

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    記述言語:英語   出版者・発行元:Biomedical Research Press  

    Although growing evidence suggests a major role for T cells in the pathogenesis of primary biliarycirrhosis (PBC), the roles of natural killer (NK) and natural killer T (NKT) cells, which predominatein the liver, in the pathogenesis of PBC remain unclear. We investigated the status ofNK and NKT cells in the liver and peripheral blood samples obtained from 11 patients with asymptomaticPBC diagnosed as stage I or II (early PBC) and 7 patients with symptomatic PBCwho underwent liver transplantation (advanced PBC) using flow cytometry and immunohistochemicalstaining. The proportions of NK and NKT cells were significantly decreased in the liver ofpatients with early PBC compared with normal donors. However, the proportion of CD56+ NKTcells was increased in the liver of patients with advanced PBC. Moreover, the proportion of activatedFas ligand (FasL)-positive NKT cells was significantly increased in the liver of patients withadvanced PBC compared with early PBC (P = 0.013). We also found increased expression of FasLon lymphocytes infiltrating around the injured bile duct in advanced PBC using immunohistochemicalstaining. Our results suggest that activated NKT cells may contribute to the biliary epithelialcell death resulting in the progression of PBC.

    DOI: 10.2220/biomedres.35.161

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    その他リンク: http://search.jamas.or.jp/link/ui/2015032875

  • Can the early bird catch the worm? Effects of the early rising on leukocyte subsets via modification of autonomic nervous system and the effect on glucose levels 査読

    Watanabe M, Ling Y, Tomiyama C, Adachi K, Mori H, Nishijo K, Abo T, Akazawa K

    Natural Science   5 ( 11 )   1133 - 1138   2013年11月

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    記述言語:英語  

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  • Research on stress-induced apoptosis of natural killer cells and the alteration of their killing activity in mouse liver 査読

    Zhen Ma, Yang Liu, Xin Zhou, Hai-Long Yu, Ming-Qi Li, Chikako Tomiyama-Miyaji, Toru Abo, Xue-Feng Bai

    World Journal of Gastroenterology   19 ( 37 )   6258 - 6264   2013年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Aim: To investigate the stress-induced apoptosis of natural killer (NK) cells and the changes in their killing activity in mouse livers. Methods: A restraint stress model was established in mice. Flow cytometry was employed to measure the percentage of NK cells and the changes in their absolute number in mouse liver. The cytotoxicity of hepatic and splenic NK cells was assessed against YAC-1 target cells via a 4 h 51Cr-release assay. Results: The restraint stress stimulation induced the apoptosis of NK cells in the liver and the spleen, which decreased the cell number. The number and percentage of NK cells in the spleen decreased. However, the number of NK cells in the liver decreased, whereas the percentage of NK cells was significantly increased. The apoptosis of NK cells increased gradually with prolonged stress time, and the macrophage-1 (Mac-1)+ NK cells were more susceptible to apoptosis than Mac-1- NK cells. Large numbers of Mac-1- NK cells in the liver, which are more resistant to stress-induced apoptosis, were observed than the Mac-1- NK cells in the spleen. The stress stimulation diminished the killing activity of NK cells in the spleen was significantly decreased, but the retention of numerous Mac-1- NK cells in the liver maintained the killing ability. Conclusion: Significant stress-induced apoptosis was observed among Mac-1+ NK cells, but not Mac-1- NK cells in the mouse liver. Stress stimulation markedly decreased the killing activity of NK cells in the spleen but remained unchanged in the liver. © 2013 Baishideng. All rights reserved.

    DOI: 10.3748/wjg.v19.i37.6258

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  • Perioperative Immunological Differentiation in Liver Cirrhotic Patients who Underwent Living Related Liver Transplantation 査読

    Yoshinobu Sato, Chikako Tomiyama, Satoshi Yamamoto, Hiroshi Oya, Takashi Kobayashi, Hidenaka Kokai, Kohei Miura, Yuki Hirose, Katsuyoshi Hatakeyama

    HEPATO-GASTROENTEROLOGY   60 ( 124 )   666 - 668   2013年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:H G E UPDATE MEDICAL PUBLISHING S A  

    Background/Aims: Liver cirrhotic patients are immunological compromised hosts. Preoperative status in cirrhotic patients affects postoperative infection complications. This study investigates the perioperative immunological changes in the differentiation by MELD score. Methodology: Fifteen patients underwent LDLT and were divided two groups, Group I (n=5, MELD score >= 20) and Group II (n=10, MELD score <20). Immunological status of cirrhotic patients was analyzed for Th1, Th2, Treg and Th17 by flow cytometry using monoclonal antibody CD3/CD19,CD4/8, FoxP3, IL-17, IFN-gamma and TNF-alpha. Results: T cell decreased and increased gradually following LDLT. The preoperative T cell count of MELD score 33 patients was very low. CD4 and CD8 T cells also decreased after LDLT. The preoperative CD8(+) T cell count of MELD score 33 patients was very low. Th17 decreased and recovered gradually in the all patients after LDLT. However Th17 of MELD score 33 did not recover. IFN-gamma-producing cells in naive T cells decreased after LDLT. Preoperatively those in the Group I was lower than those in the Group II. The population of Treg decreased in the Group I, however, it increased in the Group II on 7 days after LDLT. Conclusions: The patients with MELD score >20 showed a decrease of cytotoxic immunity with both diminution and delay of CD8+ T cells and Th17 helper T cells. The cytotoxic immunity of the patients with MELD score <20 was maintained and recovered in the early period after LDLT. The patients with MELD score >20 might be at high risk of infection after LDLT.

    DOI: 10.5754/hge

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  • Association of urinary 8-OHdG with lifestyle and body composition in elderly natural disaster victims living in emergency temporary housing 査読

    Kimie Saito, Hagiko Aoki, Naoshi Fujiwara, Masahiro Goto, Chikako Tomiyama, Yuka Iwasa

    ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE   18 ( 1 )   72 - 77   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Objectives Residents who lost land and houses due to disasterous heavy rainfall-related events on July 13, 2004 and the Chuetsu Earthquake on October 23, 2004 were moved to emergency temporary housing. The change in life style due to living under such conditions is assumed to increase oxidative stress level. In this study, we investigated the oxidative stress level in elderly residents of emergency temporary housing, and analyzed its association with lifestyle and body composition following these disasters.
    Methods A noninvasive oxidative stress marker, urinary 8-hydroxydeoxyguanosine (8-OHdG), and body composition were measured in 73 elderly residents of emergency temporary housing.
    Results In the elderly female residents, the urinary 8-OHdG level tended to decrease with time after the disasters. 8-OHdG levels were slightly higher in females than males and significantly higher among those who exercised regularly compared to those who did not, particularly in females. A weak correlation was noted between the urinary 8-OHdG level and muscle ratio in females.
    Conclusions The in vivo oxidative stress level in our study cohort of elderly residents of emergency temporary housing changed following the change in life style, but remained within the normal range. The increase in oxidative stress levels of elderly females was related to menopause. A decrease in estrogen levels due to menopause inhibits its antioxidant effects, which increases 8-OHdG levels. Although it is difficult to determine, a decrease in daily stressors over time following the disaster could be a cause of the decrease in oxidative stress levels. We suggest that the close evaluation of the stress level of disaster victims is desirable, in combination with evidence of antioxidative substances and the psychosocial influence of suffering as a consequence of the disaster.

    DOI: 10.1007/s12199-012-0284-8

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  • The effects of application of an ancient type of acupuncture needle on increase in urination of hospitalized oldest-old people. 査読

    Watanabe M, Takano O, Tomiyama C, Guan J, Hou G, Mori H, Nishijo K, Abo T, Akazawa K

    Health   5 ( 7 )   1092 - 1098   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.4236/health.2013.57147

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  • Skin rubdown with a dry towel, 'kanpu-masatsu' is an aerobic exercise affecting body temperature, energy production, and the immune and autonomic nervous systems 査読

    Mayumi Watanabe, Osamu Takano, Chikako Tomiyama, Hiroaki Matsumoto, Takahiro Kobayashi, Nobuatsu Urahigashi, Takeo Madarame, Toru Abo

    BIOMEDICAL RESEARCH-TOKYO   33 ( 4 )   243 - 248   2012年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMEDICAL RESEARCH PRESS LTD  

    Skin rubdown using a dry towel (SRDT) to scrub the whole body is a traditional therapy for health promotion. To investigate its mechanism, 24 healthy male volunteers were studied. Body temperature, pulse rate, red blood cells (RBCs), serum levels of catecholamines and cortisol, blood gases (PO2, sO(2), PCO2 and pH), lactate and glucose, and the ratio and number of white blood cells (WBCs) were assessed before and after SRDT. After SRDT, pulse rate and body temperature were increased. PO2, sO(2) and pH were also increased and there was no Rouleaux formation by RBCs. Lactate level tended to increase, whereas that of glucose did not. Adrenaline and noradrenaline levels increased, indicating sympathetic nerve (SN) dominance with increase in granulocytes. WBC number and ratio were divided into two groups according to granulocyte ratio (<= or < 60%) before SRDT: a normal group and a SN group. Only in the SN group did the granulocyte ratio decrease and the lymphocyte ratio and number increase after SRDT. It is suggested that SRDT is a mild aerobic, systemic exercise that might affect the immune system via the autonomic nervous system.

    DOI: 10.2220/biomedres.33.243

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  • Biology of autoreactive extrathymic T cells and B-1 cells of the innate immune system 査読

    Toru Abo, Chikako Tomiyama, Hisami Watanabe

    IMMUNOLOGIC RESEARCH   52 ( 3 )   224 - 230   2012年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:HUMANA PRESS INC  

    Cumulative evidence has shown that extrathymic T cells can be autoreactive and that B-1 cells may produce autoantibodies. These T and B-1 cells, which form part of the innate immune system, tend to be activated simultaneously when conventional T and B cells are in a suppressive state, for example, when thymic atrophy occurs by stress or involution with aging. In other words, autoreactive T cells and autoantibody-producing B cells are different from thymus-derived T cells and bone marrow-derived B cells. Activated extrathymic T cells and B-1 cells are often observed in numerous autoimmune diseases, aging, malarial infection and chronic graft-versus-host disease. It is thought that the autoreactivity of extrathymic T cells and B-1 cells may be important for the elimination of "abnormal self" tissues or cells. However, over-activation of innate lymphocytes may be related to the onset of disease or self-tissue destruction. However, it must be emphasized that the autoreactivity of innate lymphocytes is not generated by failure of the thymic pathway of T-cell differentiation or the conventional pathway of B-2 cells.

    DOI: 10.1007/s12026-012-8324-4

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  • Immunosuppressive function of dendritic cells existed in the liver. 査読

    Chikako Tomiyama, Hisami Watanabe, Mayumi Watanabe, Toru Abo

    Current Research in Immunology   6   1 - 7   2012年

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    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)  

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  • Suppressive role of hepatic dendritic cells in concanavalin A-induced hepatitis 査読

    C. Tomiyama, H. Watanabe, Y. Izutsu, M. Watanabe, T. Abo

    CLINICAL AND EXPERIMENTAL IMMUNOLOGY   166 ( 2 )   258 - 268   2011年11月

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    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:WILEY-BLACKWELL  

    Concanavalin A (Con A)-induced hepatitis is a mouse model of acute autoimmune hepatitis. The aim of this study was to investigate the role of hepatic dendritic cells (DC) in the immune modulation of tissue damage. Almost all hepatic DC were plasmacytoid DC (CD11c(+) I-Alow B220(+)); however, conventional DC were CD11c(+) I-Ahigh B220(-). At an early stage (3-6 h) after Con A administration, the number of DC in both the liver and spleen decreased, increasing thereafter (12-24 h) in parallel with hepatic failure. The hepatic CD11c(+) DC population contained many CD11b-cells, while the majority of splenic CD11c(+) DC were CD11b(+). After Con A administration, the proportion of I-A(+) and CD11b(+) cells within the CD11c(+) DC population tended to increase in the liver, but not in the spleen. Similarly, expression of the activation markers CD80, CD86 and CD40 by CD11c(+) DC increased in the liver, but not in the spleen. Next, adoptive transfer of DC isolated from the liver and spleen was performed 3 h after Con A administration to examine the immunomodulatory function of DC. Only hepatic DC had the ability to suppress hepatic failure. Analysis of cytokine production and subsequent identification of the effector cells showed that hepatic DC achieved this by suppressing the production of interleukin (IL)-12 and IL-2, rather than modulating effector cell function.

    DOI: 10.1111/j.1365-2249.2011.04458.x

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  • Cytokine profile of murine malaria: stage-related production of inflammatory and anti-inflammatory cytokines 査読

    Hanaa Y. Bakir, Chikako Tomiyama, Toru Abo

    BIOMEDICAL RESEARCH-TOKYO   32 ( 3 )   203 - 208   2011年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMEDICAL RESEARCH PRESS LTD  

    Balance between inflammatory and anti-inflammatory cytokines may be important in malaria presentation and outcome. To clarify cytokine interactions that produce pathology of malaria and control infection, C57BL/6 mice were infected with 10(4) parasitized RBCs from a non-lethal strain of Plasmodium yoelii. Kinetics was monitored showing the course of parasitemia, and cytokines were determined by RT-PCR from liver and spleen tissues. Inflammatory cytokines such as interferon-gamma (IFN gamma), interleukin (IL)-12, IL-6, tumor necrosis factor-alpha (TNF alpha) and anti-inflammatory cytokines, including IL-4 and IL-10, were investigated as key molecules that interact with immune cells in the activation of the immune responses. The production of IFN gamma mRNA was found to be higher on day 7 than on day 21 after infection, and IL-12 and IL-6 showed higher expression in the liver than in the spleen. Though TNF alpha was highly expressed on day 14 after infection and on day 21 in the liver, such expression was decreased on day 21 in the spleen. Anti-inflammatory cytokines showed high expression in both the liver and spleen. The results suggest that a relative balance between inflammatory and anti-inflammatory cytokines is crucial and that the increase of inflammatory cytokine levels during the acute phase of malaria may reflect an early and effective immune response. The counteraction effect of anti-inflammatory cytokines is thought to play a role in limiting progression from uncomplicated malaria to severe life-threatening complications.

    DOI: 10.2220/biomedres.32.203

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  • Metabolic conditions, hypothermia, and hypoxia induced by continuous stress are more often associated with carcinogenesis than known carcinogens. 査読

    Abo T, Watanabe M, Matsumoto H, Tomiyama C, Taniguchi T

    Medical Hypotheses and Research   7   53 - 56   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Internal environment for growth of cancer cells in mice:hypothermia, anemia and lymphocytopenia. 査読

    Watanabe M, Matsumoto H, Tomiyama C, Akazawa K, Abo T

    Health   3 ( 4 )   238 - 244   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.4236/health.2011.34042

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  • Association of glucocorticoid with stress-induced modulation of body temperature, blood glucose and innate immunity 査読

    Eisuke Kainuma, Mayumi Watanabe, Chikako Tomiyama-Miyaji, Masashi Inoue, Yuh Kuwano, HongWei Ren, Toru Abo

    PSYCHONEUROENDOCRINOLOGY   34 ( 10 )   1459 - 1468   2009年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    To know the details of the mechanism on stress-associated responses, attention was first focused on body temperature and blood glucose after stress. Mice were exposed to restraint stress for 6 h. Under this condition, hypothermia (39 degrees C -> 33 degrees C) and hyperglycemia 11150 mg/dl -> 350 mg/dl) were induced. Reflecting a stress-associated response, an increase of serum corticosterone (200 ng/ml -> up to 600 ng/ml) was observed. It was examined whether an administration of glucocorticoid induced a similar response. An injection of hydrocortisone (5.0 and 10.0 mg/mouse) simultaneously induced hypothermia and hyperglycemia. The effect on immunoparameters by an injection of hydrocortisone was examined. Although immunosuppression was seen as thymic atrophy and a decrease in the proportion of B cells in the liver, extrathymic T cells and NKT cells were found to be stress-resistant lymphocyte populations, especially in the liver. HSP70 mRNA was indicated to increase in the adrenal glands in response to the hydrocortisone injection. At( these responses, including hypothermia, hyperglycemia and immunomodulation, induced by the hydrocortisone injection were suppressed by pre-administration of a glucocorticoid receptor antagonist (RU-486). These results suggest that glucocorticoid is one of the important mediators of the stress-associated responses. (C) 2009 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.psyneuen.2009.04.021

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  • IMPACT OF FOXP3(+)CD4(+)CD25(+)T CELLS IN THE RECIPIENTS ACQUIRING ALMOST TOLERANCE AFTER LIVING DONOR LIVER TRANSPLANTATION WITH INTRA-PORTAL DONOR SPECIFIC ANTIGEN TRANSFUSION 査読

    Yoshinobu Sato, Chikako Tomiyama, Satoshi Yamamoto, Hiroshi Oya, Takashi Kobayashi, Katsuyoshi Hatakeyama

    TRANSPLANT INTERNATIONAL   22   238 - 238   2009年8月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

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  • Acute stress augments innate immunity in the liver and increases hyaluronan levels in the tissues and blood of mice 査読

    Masashi Inoue, Yuh Kuwano, Chikako Tomiyama-Miyaji, Mayumi Watanabe, Eisuke Kainuma, Hongwei Ren, Jiwei Shen, Kyosuke Miyazaki, Toru Abo

    BIOMEDICAL RESEARCH-TOKYO   30 ( 3 )   157 - 163   2009年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMEDICAL RESEARCH PRESS LTD  

    The effect of acute stress oil the immune system was examined ill mice. Restraint stress decreased the number of lymphocytes in the liver, whereas the number of lymphocytes remained unchanged in the spleen and thymus. In the liver, the decrease in number appeared at 1.5 h and fell to a third of the control level at 3 h. The proportions of IL-2R beta(+)TD3(int) cells, NKT cells, CD44(+) T cells and B cells were changed in the liver. The absolute numbers of IL-2R beta(+)CD3(int) cells, NKT cells and CD3(+)CD44(+) cells remained constant ill the liver under the stress, while those of total T cells and NK cells decreased. The levels of hyaluronan (HA) in Various tissues and sera were then examined. The expression of hyaluronan binding protein (HABP) was found to increase in the skin, liver and kidney as shown by immunohistochemical staining. An increase of HA in sera due to stress was seen at 3 h. The present results Suggest that the activation of CD44(+) T cells and unconventional T cells (i.e., innate immunity) in the blood and the elevated levels of HA (ligand for CD44) in the tissues and blood are crucial responses to acute stress exposure.

    DOI: 10.2220/biomedres.30.157

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  • Alkalization of blood pH is responsible for survival of cancer patients by mild hyperthermia 査読

    Takahiko Ohishi, Chiyoko Nukuzuma, Akira Seki, Mayumi Watanabe, Chikako Tomiyama-Miyaji, Eisuke Kainuma, Masashi Inoue, Yuh Kuwano, Toru Abo

    BIOMEDICAL RESEARCH-TOKYO   30 ( 2 )   95 - 100   2009年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMEDICAL RESEARCH PRESS LTD  

    The effect of mild hyperthermia on venous blood pH was examined in 6 cancer patients. Mild hyperthermia was induced by continuation of a rectal temperature of 39.5 degrees C for 30 min. All 6 patients were diagnosed as suffering from advanced cancer with or without surgery and chemotherapy pretreatrnents. In Cases I to 5, but not Case 6, venous blood pH was alkalized up to pH 7.7 by this mild hyperthermia and the effect was reproduced depending on the application of hyperthermia. At this time, alkalized pH was accompanied by increased PO, and decreased PCO(2) in the blood. These patients showed good physical conditions and improved clinical data. On the other hand, hyperthermia could not be continued in Case 6 due to his worsened physical condition. The present data suggest that mild hyperthermia is a useful method to improve circulation failure, physical condition and clinical data.

    DOI: 10.2220/biomedres.30.95

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  • Resistance and augmentation of innate immunity in mice exposed to starvation 査読

    Jiwei Shen, Hongwei Ren, Chikako Tomiyama-Miyaji, Mayumi Watanabe, Eisuke Kainuma, Masashi Inoue, Yuh Kuwano, Toru Abo

    CELLULAR IMMUNOLOGY   259 ( 1 )   66 - 73   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Mice were exposed to starvation for 3 days. Body temperature and various parameters were examined. By starvation, body temperature, blood glucose and ACTH decreased, especially on days 2 and 3. The level of corticosterone increased at this time. On the other hand, the number of lymphocytes yielded by the liver, spleen and thymus decreased from day 1 to 3. The change of the distribution of lymphocyte subsets was unique because NK NKT and extrathymic T cells were stress-resistant in the liver. Conventional T and B cells were stress-sensitive. Reflecting the increased proportion of NK and NKT cells, NK and NKT activities were augmented. The increased proportion of NKT cells produced both IFN gamma and IL-4 (Th0-type profile). The proportion and some functions of granulocytes and macrophages increased on Day I after starvation. These results suggest that starvation has a potential to increase the functions of unconventional lymphocytes and myeloid cells. (C) 2009 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.cellimm.2009.05.015

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  • Role of alpha-adrenergic stimulus in stress-induced modulation of body temperature, blood glucose and innate immunity 査読

    Mayumi Watanabe, Chikako Tomiyama-Miyaji, Eisuke Kainuma, Masashi Inoue, Yuh Kuwano, Hongwei Ren, Jiwei Shen, Toru Abo

    IMMUNOLOGY LETTERS   115 ( 1 )   43 - 49   2008年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Mice were exposed to restraint stress for 3 h. During this period, low body temperature (hypothermia, 39 degrees C -> less than 37 degrees C) and high blood glucose levels (hyperglycemia, 150 mg/dl -> up to 220 mg/dl) were simultaneously induced. Reflecting a stress-induced phenomenon, blood levels of catecholamines increased at that time. Administration of adrenaline (alpha-stimulus), but neither noradrenaline (alpha but less than adrenaline) nor isoproterenol (beta), induced a similar stress-induced pattern of body temperature and blood glucose variations. This a-adrenergic effect was confirmed using alpha- and beta-blockers in adrenaline-induced hypothermia and hyperglycemia. By applying this alpha-stimulus, the effect on immunoparameters was then investigated. Stress-resistant lymphocyte populations were found to be NK cells, extrathymic T cells and NKT cells, especially in the liver. Functional assays showed that both NK-cell cytotoxicity and NKT-cell cytotoxicity were augmented by alpha-stimulus. These results suggest that alpha-stimulus is one of the important factors in the stress-induced phenomenon and that it eventually produces hypothermia, hyperglycemia and innate-immunity activation seen during stress. (C) 2007 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.imlet.2007.09.010

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  • Modulation of the endocrine and immune systems by well-controlled hyperthermia equipment. 査読

    Tomiyama-Miyaji C, Watanabe M, Ohishi T, Kanda Y, Kainuma E, Bakir HY, Shen J, Ren H, Inoue M, Tajima K, Bai X, Abo T

    Biomedical research (Tokyo, Japan)   28 ( 3 )   119 - 125   2007年6月

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    担当区分:筆頭著者   記述言語:英語   出版者・発行元:Biomedical Research Press  

    Since high levels of hyperthermia induce immunosuppression to a certain extent (<I>i.e.</I>, granulocytosis and lymphocytopenia) in patients, we applied mild hyperthermia in volunteers using equipment enabling well-controlled hyperthermia. Restricted control of rectal temperature at 39.4 (± 0.2)°C for 30 min was conducted and various parameters of the body were examined. The most prominent change observed during exposure to hyperthermia was elevated levels of pH and PO<SUB>2</SUB> in the blood, even in the venous blood. A transient elevation of ACTH, cortisol and growth hormone in the blood was also seen during this time. In parallel with this phenomenon, the number of total lymphocytes and those of its subsets (especially CD57<SUP>+</SUP> or CD56<SUP>+</SUP> NK cells and NKT cells) increased. More interestingly, the proportion of HLA-DR (MHC class II antigens) increased in NK and NKT cells, and their intensity on the surface of CD20<SUP>+</SUP> B cells increased. These results suggest that mild hyperthermia is important for modulation of the functions of the circulatory, endocrine and immune systems.

    DOI: 10.2220/biomedres.28.119

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  • Concanavalin A(Con A)肝炎マウスにおける肝樹状細胞の役割

    富山 智香子[宮路], 安保 徹

    新潟医学会雑誌   121 ( 1 )   25 - 37   2007年1月

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    担当区分:筆頭著者, 責任著者   記述言語:日本語   掲載種別:学位論文(博士)   出版者・発行元:新潟医学会  

    Concanavalin A(Con A)投与により誘導される肝傷害はT細胞依存性であることは古くから知られている。しかし、肝臓には自然免疫を担うNK細胞やNKT細胞が他の臓器に比べて最も多く存在し、特異な免疫応答の場であることも明らかとなってきた。Con A肝炎モデルマウスにおいては、肝傷害のエフェクター細胞としてのT細胞、NKT細胞、Kupffer細胞、liver sinusoidal endothelial cells(LSEC)や好中球の役割、およびその機能亢進が報告されている。しかし、肝樹状細胞(DC)は肝移植におけるトレランス誘導に重要な役割を果たしていることが明らかとなり注目を浴びているが、Con A肝炎での動態は不明である。本研究では、正常マウスの肝臓より効率よくDC分画を採取する方法を確立すると共に、自己免疫性あるいは劇症肝炎モデルとして使われるCon A投与マウスの肝DCの性状と機能について解析した。その結果、正常の肝臓にはI-A-CD11clowのplasmacytoid(形質細胞様)DCが優位に存在し、その抗原提示能が低いことが明らかとなった。Con A肝炎では肝DCの総数が減少すると共に、I-A+CD11chigh CD205+のmyeloid系DCの割合が増加すること、I-A-CD11clow DC中の補助シグナル分子であるCD80とCD86の発現低下を認めた。ケモカインのmRNA発現については肝、および脾DCでCCL17が増強し、CpG刺激によるサイトカイン産生能については、MCP-1の増加、およびIL-10の低下が肝DCに特徴的であった。これらの解析から、肝傷害における病態形成への肝DCの役割の一端を明らかにできた。(著者抄録)

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  • Malaria protection in β2-microglobulin-deficient mice lacking MHC class I antigens: Essential role of innate immunity, including γδT cells. 査読

    Taniguchi T, Tachikawa S, Kanda Y, Kawamura T, Tomiyama-Miyaji C, Li C, Watanabe H, Sekikawa H, Abo T

    Immunology   122   514 - 521   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/j.1365-2567.2007.02661.x

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  • Relationship between diseases accompanied by tissue destruction and granulocytes with surface adrenergic receptors. 査読

    Abo T, Kawamura T, Kawamura H, Tomiyama-Miyaji C, Kanda Y

    Immunologic research   37 ( 3 )   201 - 210   2007年

  • Protection against malaria due to innate immunity enhanced by low-protein diet. 査読 国際誌

    Anoja Ariyasinghe, Sufi Reza M Morshed, M Kaiissar Mannoor, Hanaa Y Bakir, Hiroki Kawamura, Chikako Miyaji, Toru Nagura, Toshihiko Kawamura, Hisami Watanabe, Hiroho Sekikawa, Toru Abo

    The Journal of parasitology   92 ( 3 )   531 - 8   2006年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Mice were fed ad libitum with a normal diet (25% protein) or low-protein diets (0-12.5% protein) for a wk and then infected with a nonlethal or lethal strain of Plasmodium yoelii, that is, blood stage infection. The same diet was continued until recovery. Mice fed with a normal diet showed severe parasitemia during nonlethal infection, but survived the infection. They died within 2 wk in the case of lethal infection. However, all mice fed with low-protein diets survived without apparent parasitemia (there were small peaks of parasitemia) in cases of both nonlethal and lethal strains. These surviving mice were found to have acquired potent innate immunity, showing the expansion of NK1.1 -TCRint cells and the production of autoantibodies during malarial infection. Severe combined immunodeficiency (scid) mice, which lack TCRint cells as well as TCRhigh cells, did not survive after malarial infection of lethal strain of P. yoelii, even when low-protein diets were given. These results suggest that low-protein diets enhanced innate immunity and inversely decreased conventional immunity, and that these immunological deviations rendered mice resistant against malaria. The present outcome also reminds us of our experience in the field study of malaria, in which some inhabitants eventually avoided contracting malaria even after apparent malarial infection.

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  • Reasons why DBA/2 mice are resistant to malarial infection: expansion of CD3int B220+ gammadelta T cells with double-negative CD4- CD8- phenotype in the liver. 査読

    Bakir HY, Tomiyama-Miyaji C, Watanabe H, Nagura T, Kawamura T, Sekikawa H, Abo T

    Immunology   117 ( 1 )   127 - 135   2006年1月

  • Transient appearance of hepatic natural killer cells with high cytotoxicity and unique phenotype in very young mice. 査読

    Bai X, Wang S, Tomiyama-Miyaji C, Shen J, Taniguchi T, Izumi N, Li C, Bakir HY, Nagura T, Takahashi S, Kawamura T, Iiai T, Okamoto H, Hatakeyama K, Abo T

    candinavian Journal of Immunology   63   273 - 281   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/j.1365-3083.2006.01738.x

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  • Amelioration of acute graft-versus-host disease by NKG2A engagement on donor T cells. 査読 国際誌

    Hiroki Kawamura, Hideo Yagita, Tetsuro Nisizawa, Nakako Izumi, Chikako Miyaji, Russell E Vance, David H Raulet, Ko Okumura, Toru Abo

    European journal of immunology   35 ( 8 )   2358 - 66   2005年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Acute graft-versus-host disease (aGVHD) remains a major complication of allogeneic bone marrow transplantation, which is caused by donor T cells specific for host alloantigens. In a murine model, we found that donor T cells expressed a natural killer cell inhibitory receptor, CD94/NKG2A, during the course of aGVHD. Administration of an anti-NKG2A mAb markedly inhibited the expansion of donor T cells and ameliorated the aGVHD pathologies. These results suggested that the CD94/NKG2A inhibitory receptor expressed on host-reactive donor T cells can be a novel target for the amelioration of aGVHD.

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  • Hepatic natural killer and natural killer T cells markedly decreased in two cases of drug-induced fulminant hepatic failure rescued by living donor liver transplantation. 査読 国際誌

    Ryoko Miyakawa, Takafumi Ichida, Satoshi Yamagiwa, Chikako Miyaji, Hisami Watanabe, Yoshinobu Sato, Hisashi Yokoyama, Chika Tsukada, Yuiko Ishimoto, Satoshi Sugahara, Xiu Hua Yang, Toru Abo, Hitoshi Asakura

    Journal of gastroenterology and hepatology   20 ( 7 )   1126 - 30   2005年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The human liver contains significant numbers of innate immune cells, such as natural killer (NK) cells and natural killer T (NKT) cells, which express both T-cell receptors and NK-cell receptors simultaneously. It has been suggested that the innate immune system plays a crucial role in the liver. In this report, the distribution of NK and NKT cells in the liver and peripheral blood of two patients with drug-induced fulminant hepatic failure (FHF) who had undergone living donor liver transplantation was examined. In both the liver and peripheral blood, the proportions of NK and NKT cells markedly decreased compared with those in healthy donors. It was also revealed that, unlike murine NKT cells, human CD56(+) T cells and CD57(+) T cells did not constitutively express CD28, which is one of the important costimulatory molecules on T cells. Additionally, the residual CD56(+) T cells and CD57(+) T cells in the patients expressed more CD28 than in controls. This result suggests that NKT cells might be more activated in FHF. Although the accumulation of further cases is required, it is suggested that both NK and NKT cells might be involved in hepatic injury in FHF.

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  • Protection against malaria by anti-erythropoietin antibody due to suppression of erythropoiesis in the liver and at other sites. 査読

    Tsubata S, Ebe K, Kawamura T, Ishimoto Y, Tomiyama-Miyaji C, Watanabe H, Sekikawa H, Aoyagi Y, Abo T

    Immunol Cell Biol   83 ( 6 )   638 - 42   2005年

  • Age-dependent variation in the proportion and numer of intestinal lymphocyte subsets, especially natural killer T cells, double-positive CD4+ CD8+ cells and B220+ T cells, in mice. 査読

    Ishimoto Y, Tomiyama-Miyaji C, Watanabe H, Yokoyama H, Ebe K, Tsubata S, Aoyagi Y, Abo T

    Immunology   113 ( 3 )   371 - 377   2004年

  • Comparative characterization of double-positive CD4+8+ cells in the thymus and small intestine of mice 査読

    EBE Kazuto, TOMIYAMA-MIYAJI Chikako, YOKOYAMA Hisashi, ISHIMOTO Yuiko, TSUBATA Syunsuke, NAGURA Toru, LI ChangChun, BAI XeuFeng, KAWAMURA Toshihiko, WATANABE Hisami, AOYAGI Yutaka, ABO Toru

    Biomedical Research   25 ( 4 )   201 - 207   2004年

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    記述言語:英語   出版者・発行元:Biomedical Research Press  

    This study focused on double-positive (DP) CD4<sup>+</sup>8<sup>+</sup> cells in both the intestine and thymus. In normal mice, the proportion of DP cells in the intestine increased with aging, while that of DP cells in the thymus remained unchanged. When mice were exposed to restraint stress for 18 h, intestinal DP cells were resistant to restraint stress, while thymic DP cells were sensitive to such stress in terms of apoptotic properties. Intestinal intraepithelial lymphocytes (IEL) and thymocytes were then cultured and the number of living cells were analyzed. The number of DP cells in the thymus decreased prominently in <i>in vitro</i> culture. Interestingly, a similar phenomenon was found in intestinal DP cells in <i>in vitro</i> culture. When thymocytes were isolated from mice exposed to restraint stress, these DP cells were found to become sensitive to apoptosis in <i>in vitro</i> culture. Phenotypic characterization revealed that DP cells in the intestine were CD3<sup>+</sup>CD25<sup>−</sup>CD44<sup>+</sup>CD69<sup>+</sup>, while those in the thymus were CD3<sup>−</sup>CD25<sup>+</sup>CD44<sup>−</sup>CD69<sup>−</sup>. These results suggest that DP cells in the intestine were more mature than those in the thymus and that DP cells of IEL and thymus were generated as primitive T cells in phylogeny but later developed along independent pathways at each site.

    DOI: 10.2220/biomedres.25.201

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  • Expansion of NK1.1- intermediate TCR cells and granulocytes in mice trans-planted with TAP-1-deficient cells 査読

    IZUMI Nakako, MIYAJI Chikako, KAWAMURA Hiroki, KAWAMURA Toshihiko, ABO Toru

    Biomedical Research   25 ( 5 )   209 - 218   2004年

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    記述言語:英語   出版者・発行元:Biomedical Research Press  

    Missing self which lacked the expression of MHC class I antigens was prepared in irradiated B6.Ly5.1 mice (H-2<sup>b</sup>) which had undergone bone marrow transplantation (BMT) (depleted of T cells) of TAP-1 (−/−) (Ly5.2, H-2<sup>b</sup>) mice. Donor cells (Ly5.2<sup>+</sup>) and recipient cells (Ly5.1<sup>+</sup>) were identified by Ly5 markers. For purposes of comparison, syngeneic (B6.Ly5.2 mice) BMT and allogeneic (BALB/c mice, H-2<sup>d</sup>) BMT were also conducted. In the case of missing self cells, the ratio of expanding donor cells increased in the liver, spleen and bone marrow on days 14 and 21 after BMT. Such donor cells were mainly NK cells and NKT cells, especially in the liver. The interacting recipient lymphocytes were NKT cells at the early stage (day 7). However, the major lymphocytes became IL-2Rβ<sup>+</sup>CD3<sup>int</sup> cells which lacking NK1.1 at the fulminant stage (days 14 and 21). At this time, granulocytes expanded prominently. Since IL-2Rβ<sup>+</sup>CD3<sup>int</sup> cells (NK1.1<sup>−</sup>) lacked cytotoxicity, the suppression of expanding donor cells might be mediated by granulocytes. Granulocytes were activated by inflammatory cytokines. These results suggest that in addition to NK1.1-expressing cells (e.g., NK and NKT cells), IL-2Rβ<sup>+</sup>CD3<sup>int</sup> cells lacking NK1.1 may be also the lymphocyte subset which recognizes MHC class I-deficient self.

    DOI: 10.2220/biomedres.25.209

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  • Estimation of effector cytotoxic lymphocytes against male H-Y antigens induced by two-step stimulations as CD8+NK1.1-TCRint and CD8+NK1.1+TCRint cells 査読

    YOKOYAMA Hisashi, MIYAKAWA Ryoko, MIYAJI Chikako, TSUKADA Chika, ISHIMOTO Yuiko, KAWAMURA Hiroki, WATANABE Hisami, AOYAGI Yutaka, ABO Toru

    Biomedical Research   25 ( 2 )   93 - 100   2004年

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    記述言語:英語   出版者・発行元:Biomedical Research Press  

    C57BL/6 (B6) female mice were injected with 10<sup>7</sup> splenocytes of B6 male mice to immunize male H-Y antigens. This stimulation induced a slight increase in the proportions of CD3<sup>int</sup>IL-2Rβ<sup>+</sup> cells, CD3<sup>int</sup>NK1.1<sup>+</sup> cells (i.e., NKT cells), and CD4<sup>+</sup>T cells in the liver and spleen. However, cytotoxic activity against male H-Y antigens was not detected in hepatic and splenic lymphocytes. When these <i>in vivo</i> primed hepatic or splenic lymphocytes were cultured <i>in vitro</i> with irradiated splenocytes of male mice (i.e., mixed lymphocyte reaction, MLR), potent cytotoxicity against male H-Y antigens was induced. Unprimed (<i>in vivo</i>) hepatic and splenic lymphocytes did not acquire such activity even by <i>in vitro</i> stimulation. If the primed mice were <i>in vivo</i> stimulated again with male lymphocytes, such cytotoxicity was not obtained. In other words, <i>in vivo</i> priming and <i>in vitro</i> culture stimulation were both required for the induction of cytotoxicity. Phenotypic characterization and cell-depletion study using normal B6 mice and NKT-deficient mice revealed that effector cells were both CD8<sup>+</sup>NK1.1<sup>−</sup>TCR<sup>int</sup> and CD8<sup>+</sup>NK1.1<sup>+</sup>TCR<sup>int</sup> cells. These results suggest that recognition of H-Y antigens and effector function against H-Y antigens may be events of innate immunity similar to the case of other self-related antigens.

    DOI: 10.2220/biomedres.25.93

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  • Characterization of extrathymic CD8 alpha beta T cells in the liver and intestine in TAP-1 deficient mice. 査読 国際誌

    Chika Tsukada, Chikako Miyaji, Hiroki Kawamura, Ryoko Miyakawa, Hisashi Yokoyama, Yuiko Ishimoto, Shinobu Miyazawa, Hisami Watanabe, Toru Abo

    Immunology   109 ( 3 )   343 - 50   2003年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    TAP-1 deficient (-/-) mice cannot transport MHC class I antigens onto the cell surface, which results in failure of the generation of CD8+ T cells in the thymus. In a series of recent studies, it has been proposed that extrathymic T cells are generated in the liver and at other extrathymic sites (e.g. the intestine). It was therefore investigated whether CD8+ extrathymic T cells require an interaction with MHC class I antigens for their differentiation in TAP-1(-/-) mice. Although CD8+ thymically derived T cells were confirmed to be absent in the spleen as well as in the thymus, CD8 alpha beta+ T cells were abundant in the livers and intestines of TAP-1(-/-) mice. These CD8+ T cells expanded in the liver as a function of age and were mainly confined to a NK1.1-CD3int population which is known to be truly of extrathymic origin. Hepatic lymphocytes, which contained CD8+ T cells and which were isolated from TAP-1(-/-) mice (H-2b), responded to neither mutated MHC class I antigens (bm1) nor allogeneic MHC class I antigens (H-2d) in in vitro mixed lymphocyte cultures. However, the results from repeated in vivo stimulations with alloantigens (H-2d) were interesting. Allogeneic cytotoxicity was induced in liver lymphocytes in TAP-1(-/-) mice, although the magnitude of cytotoxicity was lower than that of liver lymphocytes in immunized B6 mice. All allogeneic cytotoxicity disappeared with the elimination of CD8+ cells in TAP-1(-/-) mice. These results suggest that the generation and function of CD8+ extrathymic T cells are independent of the existence of the MHC class I antigens of the mouse but have a limited allorecognition ability.

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  • Expansion of unconventional T cells with natural killer markers in malaria patients. 査読 国際誌

    Hisami Watanabe, Anura Weerasinghe, Chikako Miyaji, Hiroho Sekikawa, Sinichi Toyabe, M Kaiissar Mannor, Sufi Reza M Morshed, Ramesh C Halder, Jun Kobayashi, Hiromu Toma, Yoshiya Sato, Kuni Iwai, Hiroki Matsuoka, Toru Abo

    Parasitology international   52 ( 1 )   61 - 70   2003年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Immunological states during human malarial infection were examined. In parallel with parasitemia and anemia, granulocytosis was induced in the blood of patients, especially those infected with Plasmodium (P.) falciparum. At that time, the level of lymphocytes remained unchanged or slightly increased in the blood. However, the distribution of lymphocyte subsets was modulated, showing that the proportion of CD56(+)T cells, CD57(+)T cells, and gammadeltaT cells (i.e. all unconventional T cells) had increased in patients infected with P. falciparum or P. vivax. This phenomenon occurred at the early phase of infection and disappeared in the course of recovery. The data from patients with multiple attacks of P. vivax infection showed that there was no augmentation of these responses. In adult cases, the increase in the proportion of unconventional T cells seemed to closely parallel disease severity. However, all these responses were weak in children, even those infected with P. falciparum. In conjunction with accumulating evidence from mouse malaria experiments, the present results suggest that the immunological state induced by malarial infection might mainly be an event of unconventional T cells and that the immunological memory might not be long-lasting, possibly due to the properties of unconventional T cells.

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  • Immunopotentiation of intraepithelial lymphocytes in the intestine by oral administrations of beta-glucan. 査読 国際誌

    Chika Tsukada, Hisashi Yokoyama, Chikako Miyaji, Yuiko Ishimoto, Hiroki Kawamura, Toru Abo

    Cellular immunology   221 ( 1 )   1 - 5   2003年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Mice were orally administered with beta-glucan, isolated from baker's yeast, daily for one week (25mg/day/mouse) and several immunoparameters in the digestive tract were examined. The most prominent change was an increase in the number of intraepithelial lymphocytes (IEL) in the intestine, although the number of lymphocytes in the liver remained unchanged. The absolute number of both alphabetaT cells and gammadeltaT cells expressing CD8 antigens increased among IEL in the intestine. Primarily, liver lymphocytes showed a spontaneous production of Type 0 cytokine (simultaneous production of IFNgamma and IL-4) while IEL did not produce any cytokines without stimulation. However, mice administered with beta-glucan produced Type 1 cytokine, namely, production of IFNgamma alone. These results suggest that beta-glucan may be an important potentiator for mucosal immunity in the digestive tract.

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  • AIM inhibits apoptosis of T cells and NKT cells in Corynebacterium-induced granuloma formation in mice. 査読

    Kuwata.K, Watanabe.H, Jing.S-Y, Yamamoto.T, Tomiyama-Miyaji.C, Abo.T, Miyazaki.T, Naito.M

    Am. J. Pathol   ( 162 )   837 - 847   2003年

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  • Enforced expression of Bcl-2 restores the number of NK cells, but does not rescue the impaired development of NKT cells or intraepithelial lymphocytes, in IL-2/IL-15 receptor beta-chain-deficient mice. 査読 国際誌

    Masahiro Minagawa, Hisami Watanabe, Chikako Miyaji, Katsuhiro Tomiyama, Hideki Shimura, Akiko Ito, Masaaki Ito, Jos Domen, Irving L Weissman, Kazuhiro Kawai

    Journal of immunology (Baltimore, Md. : 1950)   169 ( 8 )   4153 - 60   2002年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    IL-2/IL-15Rbeta-deficient mice display impaired development of NK cells, NKT cells, and intraepithelial lymphocytes of the intestine and skin. To determine the role of survival signals mediated by IL-2/IL-15R in the development of these innate lymphocytes, we introduced a bcl-2 transgene into IL-2/IL-15Rbeta-deficient mice. Enforced expression of Bcl-2 restored the number of NK cells in IL-2/IL-15Rbeta-deficient mice, but the rescued NK cells showed no cytotoxic activity. The numbers of NKT cells and intestinal intraepithelial lymphocytes did not increase significantly, and skin intraepithelial lymphocytes remained undetectable in the bcl-2 transgenic IL-2/IL-15Rbeta-deficient mice. These results indicate an essential role of IL-2/IL-15R-mediated survival signals in the development of NK cells, but they also show that additional nonsurvival signals from IL-2/IL-15R are necessary for innate lymphocyte development.

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  • Unconventional NK1.1(-) intermediate TCR cells as major T lymphocytes expanding in chronic graft-versus-host disease. 査読 国際誌

    Ryoko Miyakawa, Chikako Miyaji, Hisami Watanabe, Hisashi Yokoyama, Chika Tsukada, Hitoshi Asakura, Toru Abo

    European journal of immunology   32 ( 9 )   2521 - 31   2002年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Chronic graft-versus-host disease (GVHD) accompanying autoimmune disease was induced in (C57BL/6xDBA/2) F(1) mice (H-2(b/d)) by an injection of splenic T cells of parental DBA/2 origin (H-2(d)). In parallel with the onset of proteinuria, an expansion of lymphocytes was induced in the liver and kidney, showing a peak at 2 weeks after the onset of disease. The majority of lymphocytes were of recipient origin (H-2(b/d)). The main lymphocyte subset among T cells at the pre-onset stage and after the onset of disease was CD8(+) NK1.1(-) CD3(int) cells (of extrathymic, hepatic origin) in both the liver and kidney. NK1.1(-) CD3(int) cells confer primarily neither NK-like nor NKT-like cytotoxicity. No induction of these types of cytotoxicity was observed in these mice with the expansion of NK1.1(-) CD3(int) cells. This raised the possibility that granulocytes induced in the liver and kidney might be associated with tissue damage. The present results suggest that, similarly to the case of autoimmune-prone mice with genetic background (e.g. MRL-lpr/lpr mice and BXSB mice), NK1.1(-) CD3(int) cells of extrathymic, hepatic origin might be crucial lymphocytes involved in the induction of the autoimmune-like disease in mice with chronic GVHD, in conjunction with Bcells (e.g. B-1 cells).

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  • Mechanisms underlying the activation of cytotoxic function mediated by hepatic lymphocytes following the administration of glycyrrhizin. 査読 国際誌

    Chikako Miyaji, Ryoko Miyakawa, Hisami Watanabe, Hiroki Kawamura, Toru Abo

    International immunopharmacology   2 ( 8 )   1079 - 86   2002年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Stronger neo-minophagen C (SNMC), a glycyrrhizin (GL) preparation, has been used for the treatment of chronic viral hepatitis. It has been reported that a single administration of SNMC induced the activation of hepatic lymphocytes in number and function in animal studies. However, it is still unknown how SNMC augments the cytotoxic function and why such augmentation of cytotoxicity occurs in the liver and other organs. In this study, SNMC was daily injected into mice (2 mg GL/day/mouse) for 2 weeks. A significant augmentation of cytotoxicity mediated by NK cells, NKT cells and TNFalpha was demonstrated mainly in the liver. The presence of TNFalpha-mediated cytotoxicity in the liver was demonstrated for the first time. In contrast to CD8+ cytotoxic T cells (CD8+ CTL), all these cytotoxicities were preexistent in lymphocytes without the immunization of a specific antigen or alloantigens. NK cytotoxicity was mediated by a perforin system, while NKT cytotoxicity was mediated by a Fas ligand system. The present results suggest that the entire cytotoxic function mediated by hepatic lymphocytes was simultaneously augmented by SNMC.

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  • Leukocyte accumulation and changes in extra-renal organs during renal ischemia reperfusion in mice. 査読 国際誌

    Shinobu Miyazawa, Hisami Watanabe, Chikako Miyaji, Osamu Hotta, Toru Abo

    The Journal of laboratory and clinical medicine   139 ( 5 )   269 - 78   2002年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Multiorgan failure is a life threatening complication in patients with ischemic acute renal failure (ARF). However, little is known about the underlying multiorgan system cellular immunity in ischemic ARF. We therefore studied the dynamics of cells accumulating in the kidneys and other organs in mice and analyzed the characteristics of the accumulated cells. We prepared a unilateral renal ischemia/reperfusion injury (IRI) model in C57BL/6 or C3H/He mice. At 1 to 3 hours after renal ischemia, increased accumulations of neutrophils and intermediate T cells were observed in the clamped kidney, but the same phenomena were also observed in the nonclamped kidney, liver, and spleen. After 24 hours, these cell numbers had returned to preischemic levels, but remained elevated for a longer period in the clamped kidney. The intermediate T cells that accumulated in the kidney and liver in the IRI mice expressed higher Vbeta chains specific to forbidden clones than in the control mice. Moreover, the accumulated intermediate T cells in the IRI liver had cytotoxic activity against both tumor cells and syngeneic thymocytes. In the clamped kidney, the accumulated intermediate T cells had less cytotoxic activity against tumor cells; however, the expression of the Fas ligand (FasL) increased, indicating a cell-mediated tissue injury via the Fas/FasL system. Histopathologically, an influx of neutrophils and lymphocytes was observed not only in the clamped kidney but also in the hepatic sinusoids concomitantly with liver dysfunction. These findings indicate that a systemic cellular immune response, including intermediate T cells, affects multiple organs during ischemic ARF, which may play an important role in the development of multiorgan failure.

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  • Identification of effector cells for TNFα-mediated cytotoxicity against WEHI164S cells 査読

    Chikako Miyaji, Hisami Watanabe, Ryoko Miyakawa, Hisashi Yokoyama, Chika Tsukada, Yuiko Ishimoto, Shinobu Miyazawa, Toru Abo

    Cellular Immunology   216 ( 1-2 )   43 - 49   2002年3月

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    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/s0008-8749(02)00525-7

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  • Association of intermediate T cell receptor cells, mainly their NK1.1(-) subset, with protection from malaria. 査読 国際誌

    A Weerasinghe, H Sekikawa, H Watanabe, K Mannoor, S R Morshed, R C Halder, T Kawamura, T Kosaka, C Miyaji, H Kawamura, S Seki, T Abo

    Cellular immunology   207 ( 1 )   28 - 35   2001年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Mice were infected with Plasmodium (P.) yoelii blood-stage parasites. Both the liver and spleen were the sites of inflammation during malarial infection at the beginning of day 7. The major expanding cells were found to be NK1.1(-) intermediate alphabetaTCR (alphabetaTCR(int)) in the liver and spleen, although the population of NK1.1(+) alphabetaTCR(int) cells remained constant or slightly increased. These TCR(int) cells are of extrathymic origin or are generated by an alternative intrathymic pathway and are distinguished from conventional T cells of thymic origin. During malarial infection, the population of conventional T cells did not increase at all. TCR(int) cells purified from the liver of mice which had recovered from P. yoelii infection protected mice from malaria when they were transferred into 6.5-Gy-irradiated mice. Interestingly, the immunity against malaria seemed to disappear as a function of time after recovery, namely, mice which had recovered from malaria 1 year previously again became susceptible to malarial infection. The present results suggest that TCR(int) cells are intimately associated with protection against malarial infection and, therefore, that mice which had recovered from malaria 1 year previously lost such immunity.

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  • Role of macrophage scavenger receptor in endotoxin shock. 査読 国際誌

    Y Kobayashi, C Miyaji, H Watanabe, H Umezu, G Hasegawa, T Abo, M Arakawa, N Kamata, H Suzuki, T Kodama, M Naito

    The Journal of pathology   192 ( 2 )   263 - 72   2000年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Lipopolysaccharide (LPS) is known to bind to several receptors on macrophages, including CD14 and macrophage scavenger receptor class A types I and II (MSR-A), and stimulates macrophages to release various inflammatory mediators. MSR-A recognizes a broad range of polyanionic ligands such as chemically modified lipoproteins, LPS of Gram-negative bacteria, and lipoteichoic acid of Gram-positive bacteria, suggesting a role in host defence. In this study, mice lacking MSR-A were used to elucidate the role of MSR-A in endotoxin shock. Peritoneal macrophages from MSR-A-deficient (MSR-A(-/-)) mice bound less remarkably to LPS than those from wild-type (MSR-A(+/+)) mice and the binding activity of MSR-A(+/+) macrophages to LPS was reduced by the addition of an anti-MSR-A antibody. Clearance of LPS in serum was retarded in MSR-A(-/-) mice after intraperitoneal administration of LPS. LPS-induced expression of cytokines in the liver was similar in MSR-A(+/+) and MSR-A(-/-) mice, but levels of interleukin (IL)-1beta expression and serum IL-1beta were lower in MSR-A(-/-) mice. Administration of large doses of LPS resulted in a higher mortality of MSR-A(+/+) mice and pretreatment with an IL-1 receptor antagonist reduced the mortality. Thus, MSR-A-mediated macrophage activation plays a negative role in protecting mice from endotoxin shock by enhancing IL-1beta production by macrophages.

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  • Functional alteration of granulocytes, NK cells, and natural killer T cells in centenarians. 査読 国際誌

    C Miyaji, H Watanabe, H Toma, M Akisaka, K Tomiyama, Y Sato, T Abo

    Human immunology   61 ( 9 )   908 - 16   2000年9月

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    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)  

    The immune system in centenarians was characterized as elevated levels in the proportion and number of granulocytes, NK cells, and extrathymic T cells (including NKT cells) in the peripheral blood. Conventional T cells, abundant in youth, were decreased in proportion and number. In addition to this numerical change in centenarians, the function was significantly altered in comparison with that in middle-aged subjects. The phagocytic function and cytokine production of granulocytes in centenarians increased whereas the production of superoxides from granulocytes decreased. This tendency was almost the same in both healthy and unhealthy centenarians. IFN gamma production by NK and extrathymic T cells in centenarians seemed to be augmented and resulted in an elevated level of serum IFN gamma. Possibly due to the effect of this endogenous IFN gamma, the proportion of CD64(+) (Fc gamma RI) cells among granulocytes was elevated. The expansion of CD64 antigens on granulocytes is known to be regulated by IFN gamma and to be associated with their induction of phagocytosis. These results suggest that the immune system of centenarians is not merely impaired, but altered in terms of the number and functions of granulocytes, NK cells, NKT cells.

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  • Suppressive effect of antiulcer agents on granulocytes--a role for granulocytes in gastric ulcer formation. 査読 国際誌

    T Kawamura, C Miyaji, S Toyabe, M Fukuda, H Watanabe, T Abo

    Digestive diseases and sciences   45 ( 9 )   1786 - 91   2000年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Many clinicians have believed that H2-blockers and proton pump inhibitors ameliorate gastric ulcers via their antacid function. We examined the effects of these antacids on granulocytes. Gastric ulcer patients were administered an H2-blocker or proton pump inhibitor for a week and the number of granulocytes and the superoxide production were examined. To determine the trafficking of granulocytes, mice were exposed to restraint stress for 24 hr. The H2-blocker decreased the number of granulocytes, while the proton pump inhibitor suppressed their superoxide production in humans and mice. The major function of H2-blockers and proton pump inhibitors in curing gastric ulcers seems to be their suppressive effects on granulocytes. In this case, stress accelerates the trafficking of granulocytes from the bone marrow to the gastric mucosa. If we demonstrate a role for granulocytes in gastric ulcer formation, an gap in the acid-pepsin theory and the Helicobacter pylori theory is filled in.

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  • Disparate effect of beige mutation on cytotoxic function between natural killer and natural killer T cells. 査読 国際誌

    M Bannai, H Oya, T Kawamura, T Naito, T Shimizu, H Kawamura, C Miyaji, H Watanabe, K Hatakeyama, T Abo

    Immunology   100 ( 2 )   165 - 9   2000年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Beige mice lack natural killer (NK) cytotoxicity, although NK cells are normally present. In recent studies, NK T cells have been newly identified. We therefore examined the number and function of NK T cells in beige mice. The number of NK T cells was at a normal level in the liver of beige mice. NK cytotoxicity was decreased in the liver of these mice, whereas NK T cytotoxicity was intact. When immunochemical staining for perforin was conducted, the majority of NK cells and the minority of NK T cells in beige mice carried a giant granule, containing perforin, in the cytoplasm. In the case of control B6 mice, the majority of NK cells and the minority of NK T cells had multiple, dispersed granules containing perforin. These results suggest that NK T cytotoxicity is unaffected by the beige mutation, owing to their cytotoxicity being mediated without the secretion system of perforin.

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  • Resistance of extrathymic T cells to stress and the role of endogenous glucocorticoids in stress associated immunosuppression. 査読 国際誌

    T Shimizu, T Kawamura, C Miyaji, H Oya, M Bannai, S Yamamoto, A Weerasinghe, R C Halder, H Watanabe, K Hatakeyama, T Abo

    Scandinavian journal of immunology   51 ( 3 )   285 - 92   2000年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    When mice were exposed to restraint stress for 12 or 24 h, severe lymphopenia was induced in all immune system organs, including the liver and the thymus. However, in adrenalectomized mice, this response was completely absent. Phenotypic characterization revealed that interleukin (IL)-2Rbeta+CD3int cells (i.e. extrathymic T cells) with CD4+ phenotype and the NK1.1+ subset of CD3int cells (i.e. NKT cells) in the liver as well as the mature conventional T cells in the thymus were resistant to such stress. In adrenalectomized mice, there was no significant change in the distribution of lymphocyte subsets in all tested organs before stress. Interestingly, the number of lymphocytes in the liver and spleen and the proportion of NKT cells in the liver rather increased after stress in these adrenalectomized mice. Therefore, endogenous steroid hormones were indicated to be important in the induction of immunosuppressive states after stress. Among stress associated cytokines, the secretion of tumour necrosis factor (TNF)-alpha was completely suppressed while that of IL-6 was partially suppressed in adrenalectomized mice. These results suggest that endogenous steroid hormones are important for the induction of the stress associated immunosuppression and that NKT cells are resistant to stress, namely, resistant to exposure to endogenous steroid hormones.

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  • CD4+ and/or gammadelta+ T cells in the liver spontaneously produce IL-4 in vitro during the early phase of Leishmania major infection in susceptible BALB/c mice. 査読 国際誌

    T Yamashita, H Miyata, C Miyaji, H Watanabe, T Abo, T Kobayakawa, A Kaneko, F Sendo

    Acta tropica   73 ( 2 )   109 - 19   1999年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Numerous studies on the cytokine production profile in Leishmania major infected susceptible and resistant mice have been carried out to elucidate the mechanisms of healing or non-healing of this infection. However, many methods may have failed to detect the actual cytokine production in the inflammatory foci. To overcome this problems, the ELISPOT assay was used to examine the spontaneous production of IL-4 and IFN-gamma in vitro by mononuclear cells from the spleen, lymph nodes and liver in L. major-infected susceptible BALB/c and resistant C57BL/6 mice. None of these mononuclear cells spontaneously produced IFN-gamma in either mouse strains in vitro in the absence of the corresponding antigen(s). However, liver mononuclear cells from infected BALB/c mice spontaneously produced IL-4 in vitro in as early as 2 weeks after the infection, but this was not observed in C57BL/6 mice. The IL-4 producing liver lymphocytes consisted of CD4+ and/or gammadelta+ T cells and uncharacterized cells. These results suggest that liver lymphocytes play some role in the establishment of Th2 prevalence in susceptible BALB/c mice, based on the importance of IL.4 production in the early phase of L. major infection in establishing Th2 dominance in this parasite susceptible mouse.

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  • Development of intraepithelial T lymphocytes in the intestine of irradiated SCID mice by adult liver hematopoietic stem cells from normal mice. 査読 国際誌

    S Yamagiwa, S Seki, K Shirai, Y Yoshida, C Miyaji, H Watanabe, T Abo

    Journal of hepatology   30 ( 4 )   681 - 8   1999年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND/AIMS: We recently reported the adult mouse liver to contain c-kit+ stem cells that can give rise to multilineage leukocytes. This study was designed to determine whether or not adult mouse liver stem cells can generate intraepithelial T cells in the intestine as well as to examine the possibility that adult liver c-kit+ stem cells originate from the fetal liver. METHODS: Adult liver mononuclear cells, bone marrow (BM) cells, liver c-kit+ cells or bone BM c-kit+ cells of BALB/c mice were i.v. transferred into 4 Gy irradiated CB17/-SCID mice. In other experiments, fetal liver cells from Ly5.1 C57BL/6 mice and T cell depleted adult BM cells from Ly5.2 C57BL/6 mice were simultaneously transferred into irradiated C57BL/6 SCID mice (Ly5.2). At 1 to 8 weeks after cell transfer, the SCID mice were examined. RESULTS: Not only BM cells and BM c-kit+ cells but also liver mononuclear cells and liver c-kit+ cells reconstituted gamma delta T cells, CD4+ CD8+ double-positive T cells and CD8 alpha+beta- T cells of intestinal intraepithelial lymphocytes of SCID mice. Injection of a mixture of fetal liver cells from Ly5.1 C57BL/6 mice and adult BM cells from Ly5.2 C57BL/6 mice into Ly5.2 C57BL/6 SCID mice induced both Ly5.1 and Ly5.2 T cells, while also generating c-kit+ cells of both Ly5.1 and Ly5.2 origins in the liver. CONCLUSIONS: Adult mouse liver stem cells were able to generate intestinal intraepithelial T cells of the SCID mice, and it is thus suggested that some adult liver stem cells may indeed be derived from the fetal liver.

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  • Abundance of NKT cells in the salivary glands but absence thereof in the liver and thymus of aly/aly mice with Sjögren syndrome. 査読 国際誌

    J Narita, T Kawamura, C Miyaji, H Watanabe, S Honda, T Koya, M Arakawa, T Abo

    Cellular immunology   192 ( 2 )   149 - 58   1999年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    It is known that ALY/Nsc Jcl-aly/aly (aly/aly) mice that congenitally lack lymph nodes fall victim to Sjögren syndrome as a function of age. We investigated how TCRint cells of extrathymic origin and TCRhigh cells of thymic origin are distributed in various organs of these mice. Although the distribution of T-cell subsets was not different between control aly/+ and aly/aly mice in youth in any of the tested organs, the proportion of TCRint cells in the liver and spleen of aly/aly mice increased with aging. Usually, TCRint cells in the liver comprise a half-and-half mixture of a NK1. 1(+) subset (i.e., NKT cells) and a NK1.1(-) subset. In constrast, almost all expanding TCRint cells in various immune organs of aly/aly mice were found to be NK1.1(-). A large proportion of lymphocytes, including NK cells and TCRint cells, were also present in the salivary glands of aly/aly mice. Interestingly, these TCRint cells in the salivary glands contained an NK1.1(+) subset (i.e., NKT cells) that used an invariant chain of Valpha14Jalpha281 for TCRalphabeta (>50%). Moreover, gammadeltaT cells that used Vgamma 1, 2, 4/Vdelta 1, 4, 6 mRNAs, different from those of gammadeltaT cells in the liver and intestine, were abundant. Possibly reflecting the in situ generation of these T cells in the salivary glands, the expression of RAG-2 mRNA was evident by the RT-RCR method. These results suggest that (i) inflammatory lymphocytes that evoke Sjögren syndrome in aly/aly mice are NK cells or TCRint cells (both NK1.1(+) and NK1.1(-) subsets) and (ii) TCRint cells in the salivary glands might be generated in situ.

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  • Mutations in the p53 and scid genes do not cooperate in lymphomagenesis in doubly heterozygous mice. 査読 国際誌

    S Kosugi, T Miyazawa, D Chou, Y Saito, T Shinbo, A Matsuki, H Okano, C Miyaji, H Watanabe, K Hatakeyama, O Niwa, R Kominami

    Biochemical and biophysical research communications   255 ( 1 )   99 - 103   1999年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Analysis of double mutant mice of the p53 and scid genes, which have a combination of cell cycle checkpoint/apoptosis and DNA repair defects, shows that the latter defect synergistically enhances lymphoma development with loss of the former function. These mice lack the ability to eliminate lymphocytes predisposed to neoplastic transformation resulting from faulty antigen receptor gene rearrangement. Here we examine the cooperativity in double heterozygotes of p53 and scid in which normal development of lymphocytes is not impaired. MSM mice carrying a p53-knockout allele were crossed with BALB/c mice heterozygous for the scid locus and 129 offspring were obtained. They were subjected to gamma-ray irradiation, 84 thymic lymphomas being generated. The tumors and host mice were genotyped of p53 and scid. Among 42 mice developing p53-deficient lymphomas, scid/+ and +/+ genotypes did not provide difference in onset and latency. Besides, allelic loss of the Scid gene occurred at a high frequency in those lymphomas but the loss exhibited no allelic bias. The results suggest that the scid/+ genotype is not a modifier of loss of p53 function in the double heterozygotes.

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  • Differentiation of forbidden T cell clones and granulocytes in the parenchymal space of the liver in mice treated with estrogen. 査読 国際誌

    J Narita, C Miyaji, H Watanabe, S Honda, T Koya, H Umezu, T Ushiki, S Sugahara, T Kawamura, M Arakawa, T Abo

    Cellular immunology   185 ( 1 )   1 - 13   1998年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Estrogen was administered to B6 (NK1.1+ strain), BALB/c (Mls-1b2a, V beta 3+ cells being forbidden clone), or (B6 x BALB/c) F1 mice (1 mg/mouse). On days 3 and 10, the number of cells yielded by the liver doubled, whereas that yielded by the thymus decreased prominently. The numbers of cells in the spleen, bone marrow, and blood were unchanged. c-kit+ stem cells, which give rise to multilineage cells, were present in the liver and bone marrow. The proportion of such c-kit+ cells in the liver increased while that in the bone marrow decreased on day 3. Therefore, the absolute number of c-kit+ stem cells increased severalfold in the liver and clusters of lymphoid cells became visible in the parenchymal space. At that time, the expression of recombination activating gene-1 and -2 mRNAs became prominent. Reflecting these phenomena, the number and proportion of IL-2R beta+ CD3int cells (i.e., primordial T cells) increased in the liver on days 3 and 10. An increase in the number of proportion of such CD3int cells was seen even in the thymus and uterus. In parallel with the increase of CD3int cells, the proportion of granulocytes also increased in various organs on day 3. Forbidden clones were present in either the NK1.1+ or the NK1.1- subset of CD3int cells in (B6 x BALB/c) F1 mice treated with estrogen and liver mononuclear cells in such mice acquired potent cytotoxicity against syngeneic thymocytes. These results reveal that estrogen has the ability to potentiate the generation of self-reactive T cells and granulocytes in the liver and other organs.

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  • Numerical and functional characteristics of lymphocyte subsets in centenarians. 査読 国際誌

    C Miyaji, H Watanabe, M Minagawa, H Toma, T Kawamura, Y Nohara, H Nozaki, Y Sato, T Abo

    Journal of clinical immunology   17 ( 5 )   420 - 9   1997年9月

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    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)  

    The immune system in the aged is a very interesting subject for study. In this study, analysis was extended to extrathymic T cells as well as NK cells and "conventional" T cells (i.e., thymus-derived T cells) in terms of their constitution and function in both healthy and unhealthy centenarians. Middle-aged persons were used as controls. Healthy and unhealthy centenarians showed lower levels in the proportion and absolute number of lymphocytes. The major change in the constitution of lymphocyte subsets was increased levels in the proportion of NK cells (CD56+/CD57+) and extrathymic T cells (CD3+CD57+). Inversely, conventional T cells decreased in proportion and function (i.e., proliferative response to mitogen). Although NK cells increased in centenarians, NK activity by whole lymphocytes and the purified NK fraction decreased. The difference between healthy and unhealthy centenarians was small in all parameters, the only difference being a lower level of expression of CD56 antigens on CD57+ T cells in unhealthy centenarians. These results indicate that there is a major shift in lymphocyte population from conventional T cells to NK cells and extrathymic T cells with aging. Concerning the age-associated increases in CD56+ T and CD57+ T cells, these cells correspond to NK1+ T cells in mice.

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  • c-kit+ stem cells and thymocyte precursors in the livers of adult mice. 査読 国際誌

    H Watanabe, C Miyaji, S Seki, T Abo

    The Journal of experimental medicine   184 ( 2 )   687 - 93   1996年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Livers of the adult mice contain c-kit+ stem cells that can reconstitute thymocytes, multiple lineage cells, and bone marrow (BM) stem cells. Transfer of 1 x 10(7) hepatic mononuclear cells (MNC) and 5 x 10(4) hepatic c-kit+ cells of BALB/c mice induced DP thymocytes within a week in four Gy-irradiated CB17/-SCID mice, but 2 wk were required for BM cells or BM c-kit+ cells to produce DP thymocytes. Moreover, B cell-depleted BM cells or liver MNC of SCID mice that had been rescued by hepatic MNC of BALB/c mice again reconstituted thymus and B cells of other irradiated SCID mice. CD3- IL-2R beta- populations of both BM cells and hepatic MNC of C57BL/6 (B6) mice could generate T cells with intermediate TCR (mostly NK1.1-) in the liver of irradiated B6 SCID mice before thymic reconstitution (extrathymic T cells). Furthermore, transfer of liver c-kit+ cells of B6-Ly 5.1 mice into irradiated B6 SCID (Ly5.2) mice revealed that liver c-kit+ cells can reconstitute myeloid and erythroid lineage cells. These results strongly suggest that the liver contains pluripotent stem cells and serves an important hematopoietic organ even into adulthood.

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  • A comparison of proliferative response to IL-7 and expression of IL-7 receptors in intermediate TCR cells of the liver, spleen, and thymus. 査読 国際誌

    C Miyaji, H Watanabe, Y Osman, Y Kuwano, T Abo

    Cellular immunology   169 ( 2 )   159 - 65   1996年5月

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    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)  

    It is well established that IL-7 supports the earliest differentiation of both T and B cells in fetal and adult life. On the other hand, mature lymphocyte subsets tend to decrease the response to IL-7 in case of T and B cells. In a recent study, NK1.1+ T cells in the thymus are also found to efficiently respond to IL-7 and express IL-7 receptors (IL-7R). This population is generated through an alternative intrathymic pathway. A similar population, namely, T cells with intermediate levels of TCR (i.e., int TCR cells) are known to be generated through extrathymic pathways. In this respect, the proliferative response to IL-7 and the expression of IL-7R in int TCR cells of various organs were compared. Whole liver MNC and isolated int TCR cells from the liver were found to proliferate in response to IL-7. Moreover, a considerable population of int TCR cells in both the liver and thymus were found to carry a higher density of IL-7R on the surfaces than high TCR cells. More precisely, the intensity of IL-7R on int TCR cells in the thymus was the highest but those on int TCR cells in other organs were slightly lower (i.e., int TCR cells in the thymus greater than int TCR cells in the liver greater than high TCR cells). Taken together with the result of expression of IL-7 mRNA by hepatocytes and thymic tissues, it is concluded that IL-7 is one of the most important growth factors for int TCR cells both in the liver and thymus.

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  • Therapeutic effects of glycyrrhizin in mice infected with LP-BM5 murine retrovirus and mechanisms involved in the prevention of disease progression. 査読 国際誌

    H Watanbe, C Miyaji, M Makino, T Abo

    Biotherapy (Dordrecht, Netherlands)   9 ( 4 )   209 - 20   1996年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Glycyrrhizin (GL), a plant extract, has been evaluated for its inhibitory effect on HIV replication in vitro and for its improvement of clinical symptoms in HIV-infected patients. In this study, we used GL in a murine AIDS model (MAIDS) to evaluate these effects. C57BL/6 mice were inoculated with LP-BM5 murine leukemia virus to cause MAIDS. Treatment with GL supplemented with glycine and cysteine (Stronger Neo-Minophagen C, SNMC) was then begun on day 0 or 4 wks after virus inoculation. SNMC was administered three times a week for up to 19 wks. Immunological abnormalities were monitored with respect to the surface phenotype identified by two-color staining for CD3 and IL-2 receptor beta-chain. All mice infected with the virus alone developed MAIDS and died by 14 wks after infection. The immunopathogenesis was estimated to be an abnormal expansion of intermediate CD3 cells (i.e., extrathymic T cells) as well as other types of lymphocytes. SNMC did not change the total mortality rate. However, some mice that began the treatment on day 0 or 4 wks after infection survived 3 wks longer. Splenomegaly and lymphadenopathy in such mice were suppressed. These mice showed normal phenotypic features and normal responses to Con A. These results suggest that SNMC is effective in some MAIDS mice in preventing the progression of disease. When lymphocytes isolated from the liver, spleen and lymph nodes of diseased mice were cultured in vitro, they showed a spontaneous proliferation. Interestingly, such proliferation was inhibited by addition of liver lymphocytes, but not splenic lymphocytes, obtained from normal or SNMC-treated mice. Since liver lymphocytes contains intermediate CD3 cells with autoreactivity, they may possibly suppress the progression of disease.

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  • Relationships between intermediate TCR cells and NK1.1+ T cells in various immune organs. NK1.1+ T cells are present within a population of intermediate TCR cells. 査読 国際誌

    H Watanabe, C Miyaji, Y Kawachi, T Iiai, K Ohtsuka, T Iwanage, H Takahashi-Iwanaga, T Abo

    Journal of immunology (Baltimore, Md. : 1950)   155 ( 6 )   2972 - 83   1995年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Experiments to date have revealed a population of T cells that carry intermediate (int) levels of TCR (or CD3) and express IL-2R beta-chain (IL-2R beta) in mouse liver. Such int TCR cells also reside in other immune organs, although in low numbers. On the other hand, NK1.1+ T cells with int TCR do reside in the thymus and other peripheral organs. To determine the relationship of two types of cells, we characterized int CD3 cells and NK1.1+ T cells throughout the organs in terms of the phenotype, V beta repertoire, and morphology. Although both IL-2R beta+ T cells and NK1.1+ T cells are classified as int CD3 cells, NK1.1+ T cells are present within int CD3 cells. The majority of int CD3 cells in the liver and thymus were NK1.1+, whereas the minority of such cells in the spleen, lymph nodes, and bone marrow were NK1.1+. Among int CD3 cells, double-negative (DN) CD4-8- cells and/or CD4+ were abundant in NK1.1+ subset, whereas CD8+ cells were generally abundant in NK1.1- subset. Self-reactive V beta+ clones estimated by the M1s system were distributed to both NK1.1+ and NK1.1- subsets. High CD3 cells in the thymus and other organs contained neither DN cells nor forbidden clones. Int CD3 cells had the morphology of granular or agranular lymphocytes carrying perforin. Among int CD3 cells, NK1.1+ subset had a higher level of perforin-positive cells than NK1.1- subset. These results clearly demonstrate the relationship between int TCR cells and NK1.1+ T cells in various organs.

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書籍等出版物

  • 安保徹の原著論文を読む―膠原病、炎症性腸疾患、がんの発症メカニズムの解明

    渡邉 まゆみ, 富山 智香子( 担当: 共訳)

    三和書籍  2013年2月  ( ISBN:4862511473

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    総ページ数:470  

    CiNii Books

    ASIN

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MISC

  • 体温、白血球の自律神経支配、エネルギー産生への影響 新温熱刺激-ナノミストサウナ-を用いて 査読

    渡邉 まゆみ, 富山 智香子, 本間 隆, 稲田 昭弘, 早川 陽喜, 安保 徹

    日本温泉気候物理医学会雑誌   74 ( 2 )   96 - 102   2011年2月

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    記述言語:日本語   出版者・発行元:(一社)日本温泉気候物理医学会  

    健常男性6名(平均46.5歳)を対象に、20分間のナノミストサウナ(NMS)で40℃の温熱刺激を行い、その前後で各種パラメーターを計測した。NMS刺激前後で体温は36.8→37.2℃、静脈酸素分圧PO2は52→61mmHgと有意に上昇し、静脈血pHは7.42→7.44と上昇傾向を示し、乳酸値は3.7→3.2mmo/Lと有意に減少した。末梢血リンパ球の割合ではNK細胞(CD56陽性細胞)は21.8→17.7%と有意に減少し、B細胞(CD19陽性細胞)は11.3→13.4%と有意に上昇、T細胞(CD3陽性細胞)は増加傾向を示した。血液1μL中の各リンパ球サブセットの絶対数ではNK細胞数は498→436/μLと有意に減少し、B細胞数は261→349/μLと有意に増加、T細胞数は増加傾向を示し、白血球総数は5167→5433/μLと有意に増加した。乳酸値の低下は交感神経緊張の抑制状態と考えられ、NMS温熱刺激は体への負担がなく、白血球の活性化による免疫増強手段として有用と考えられた。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J01036&link_issn=&doc_id=20110302050003&doc_link_id=%2Fck1onsen%2F2011%2F007402%2F004%2F0096-0102%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fck1onsen%2F2011%2F007402%2F004%2F0096-0102%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • マラリア原虫に対する宿主応答を中心として 東南アジアの熱帯熱マラリア患者におけるNKT及びγδT細胞サブセットの解析(Analysis of NKT and γδT cell subsets in patients with falciparum malaria in South-east Asia)

    Taniguchi Tomoyo, Mannoor Kaiissar, Li ChangChun, Tomiyama-Miyaji Chikako, Kobayashi Fumie, Watanabe Hisami

    日本免疫学会総会・学術集会記録   36   111 - 111   2006年11月

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    記述言語:英語   出版者・発行元:(NPO)日本免疫学会  

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  • 生体肝移植症例における肝内樹状細胞の経時的検討

    山際 訓, 富山 智香子, 渡部 久実, 市田 隆文, 松田 康伸, 高村 昌昭, 本田 穣, 佐藤 好信, 青柳 豊

    消化器と免疫   ( 42 )   146 - 149   2006年4月

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    記述言語:日本語   出版者・発行元:日本消化器免疫学会  

    生体肝移植症例の移植肝生着とDCとの関連性について検討することを目的とし,移植前後で経時的に肝臓内樹状細胞(DC)の変動を解析した.生体肝移植を施行したレシピエント12例,およびそのドナー12例を対象とした.移植後の拒絶反応の有無は,血液生化学的データと肝生検による病理組織学的検討により診断した.肝組織および末梢血よりFicoll比重遠心法でリンパ球を分離後,各種蛍光モノクローナル抗体で染色しフローサイトメトリーで解析した.正常肝内DCは成熟あるいは活性化型が多く,未熟型が多い末梢血中DCとは異なるフェノタイプを示した.拒絶反応の有無により移植肝内DCの違いを認め,移植肝生着に関与していることが示唆された

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  • 【Innate immunityと肝病態】自然免疫の制御による肝疾患治療の可能性 自然免疫制御による移植肝に対する免疫寛容誘導

    富山 智香子, 佐藤 好信, 渡部 久実, 山際 訓, 市田 隆文

    肝胆膵   52 ( 4 )   607 - 615   2006年4月

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    担当区分:筆頭著者   記述言語:日本語   出版者・発行元:(株)アークメディア  

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  • 【わが国における肝移植の現況と展望】免疫抑制療法の現況と今後の展開

    佐藤 好信, 渡部 久実, 山本 智, 中塚 英樹, 竹石 利之, 大矢 洋, 小林 隆, 渡辺 隆興, 島村 和彦, 宮路 智香子, 安保 徹, 畠山 勝義

    消化器外科   25 ( 3 )   337 - 346   2002年3月

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    記述言語:日本語   出版者・発行元:(株)へるす出版  

    肝移植の免疫抑制療法の現況と,著者等が成人生体肝移植で行っているドナー血門脈内反復投与の,臨床成績及びNKT細胞やキメリズムの点からの免疫学的解析について述べた.現在の肝移植における免疫抑制療法は,成績からいっても概ね良好で安定期に入っているといっても過言ではない.しかし肝癌やウイルス性肝硬変等の適応疾患の拡大,ABO不適合移植の問題,免疫抑制剤の副作用の問題など未解決の問題が出てきており,よりきめ細かいそれらの問題に対処しうる新しい免疫抑制療法の開発が望まれている.ドナー血門脈内投与はそれらの問題を解決しうる,そして新しい展開を与えてくれる優れた免疫抑制療法であるといえる

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  • 免疫機能検査 高齢者の免疫機能

    渡部 久実, 宮路 智香子, 安保 徹

    臨床検査   45 ( 1 )   81 - 87   2001年1月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

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  • 肝再生/肝関連リンパ球 Adultマウス肝に存在するc-kit+造血幹細胞からのin vitroにおける細胞分化誘導

    宮路 智香子, 渡部 久実, 関 修司, 安保 徹

    肝類洞壁細胞研究の進歩   11   122 - 125   1999年12月

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    担当区分:筆頭著者   記述言語:日本語   出版者・発行元:(株)アークメディア  

    成体肝は骨髄と同様な造血幹細胞ばかりでなく,T細胞をより早く分化させる前駆細胞をも有し,そこから局所でint TCR細胞やNKT細胞を分化させ得ると考えられた.又,これらの細胞の出現にはMHC class I或いはその関連分子の何らかの関与が示唆される

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  • スカベンジャー受容体 LPS肝障害におけるスカベンジャー受容体の機能解析

    小林 義昭, 内藤 眞, 渡部 久実, 宮路 智香子, 安保 徹, 荒川 正昭, 下条 文武, 鈴木 宏志, 児玉 龍彦

    肝類洞壁細胞研究の進歩   11   22 - 25   1999年12月

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    記述言語:日本語   出版者・発行元:(株)アークメディア  

    マクロファージスカベンジャー受容体(MSR-A)はlipopolysaccharide受容体の一つとして機能し,MSR-Aを介したシグナルはマクロファージ活性化機構に関与する

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  • NKT細胞

    宮路 智香子, 安保 徹

    検査と技術   27 ( 4 )   406 - 409   1999年4月

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    担当区分:筆頭著者   記述言語:日本語   出版者・発行元:(株)医学書院  

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  • 【NK細胞をめぐって】NKT細胞の胸腺外分化と活性化機構

    宮路 智香子, 渡部 久実, 安保 徹

    臨床免疫   31 ( 1 )   14 - 20   1999年1月

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    担当区分:筆頭著者   記述言語:日本語   出版者・発行元:(有)科学評論社  

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  • サイトカインの基礎と臨床応用 胸腺外分化T細胞の分化とサイトカイン

    宮路 智香子

    新潟医学会雑誌   112 ( 11 )   671 - 675   1998年11月

  • LPS吸入マウスにおける肺のリンパ球の解析

    小屋 俊之, 成田 淳一, 渡部 久実, 宮路 智香子, 本田 茂, 荒川 正昭, 安保 徹

    日本臨床免疫学会会誌   ( 26回抄録集 )   96 - 96   1998年10月

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    記述言語:日本語   出版者・発行元:日本臨床免疫学会  

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  • 【NK細胞とNKT細胞】NKT細胞の起源とその分化機構

    渡部 久実, 宮路 智香子, 安保 徹

    組織培養工学   24 ( 8 )   303 - 308   1998年7月

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    記述言語:日本語   出版者・発行元:(株)ニュー・サイエンス社  

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  • マウスAIDSモデル(MAIDS)におけるSNMCの効果

    渡部 久実, 宮路 智香子, 牧野 正彦

    Minophagen Medical Review   43 ( 2 )   93 - 100   1998年3月

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    記述言語:日本語   出版者・発行元:(株)ミノファーゲン製薬  

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  • リンパ球に関する話題 第4のリンパ球としてのNKT細胞

    宮路 智香子, 安保 徹

    Surgery Frontier   4 ( 4 )   365 - 368   1997年12月

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    担当区分:筆頭著者   記述言語:日本語   出版者・発行元:(株)メディカルレビュー社  

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  • 【肝臓のリンパ球】Adultマウス肝に存在するLin- c-kit+幹細胞の解析

    宮路 智香子

    Minophagen Medical Review   42 ( 6 )   319 - 323   1997年11月

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    記述言語:日本語   出版者・発行元:(株)ミノファーゲン製薬  

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  • 胸腺外分化T細胞と加齢

    渡部 久実, 宮路 智香子, 安保 徹

    病理と臨床   15 ( 5 )   453 - 459   1997年5月

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    記述言語:日本語   出版者・発行元:(株)文光堂  

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  • 肝臓における胸腺外分化T細胞の動態と造血幹細胞

    渡部 久実, 宮路 智香子, 安保 徹

    Minophagen Medical Review   42 ( 3 )   153 - 158   1997年5月

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    記述言語:日本語   出版者・発行元:(株)ミノファーゲン製薬  

    著者等の解析で,intTCR細胞中にはNK1.1+細胞サブセット(NK1+T細胞)とNK1.1-細胞サブセットが存在し,しかもその細胞構成が異なることが明らかにされた.intTCR細胞とNK1+T細胞は,細胞表面形質,分布,形態,細胞障害活性,禁止クローンの存在など,いずれも類似しており,NK細胞と胸腺由来のconventional T細胞の中間に位置するリンパ球であるといえる.一方,肝臓は独自の造血幹細胞を有し,胸腺外分化T細胞を分化・成熟させることも明らかとなってきた.また,腸管の基底部(crypt lamina propria)には腸管上皮内リンパ球の前駆細胞が見いだされている.このように,胸腺外分化T細胞の前駆細胞がそれぞれの器官に存在することから,胸腺のみがT細胞分化の場であるという考えは大きく変わりつつある

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  • Paradoxical Effects of Glycyrrhizin on the Induction of Granulocytesand Extrathymic T Cells between Normal Mice and Mice with PreexistingGranulocytosis

    Soichiro YAMAMURA, Chikako MIYAJI, Hisami WATANABE

    Acta medica et biologica   44 ( 4 )   177 - 185   1996年12月

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    記述言語:英語   出版者・発行元:新潟大学  

    Some traditional Chinese medicines are known to have paradoxical effects. For example, one such medicine (i.e., glycyrrhizin) is effective for the treatment of allergic diseases (i.e., lymphocyte-associated inflammation), and is also sometimes effective for the treatment of suppurative diseases (i.e., granulocyte-associated inflammation). To investigate the mechanisms underlying this paradox, we conducted a study in mice. When normal mice were administered with one i. p. injection of glycyrrhizin, granulocytes and extrathymic T cells increased in proportion and number in various immune organs. However, an opposite response of glycyrrhizin was induced with such an injection in mice with preexisting granulocytosis. These mice included those treated with G-CSF and AIDS mice infected with murine leukemia virus. In other words, glycyrrhizin reduced the levels of granulocytes and extrathymic T cells in various organs of mice with preexisting granulocytosis. These results suggest that some drugs have the ability to exert paradoxical effects, depending on the conditions of the host immune system. The underlying mechanisms are discussed.

    CiNii Article

    CiNii Books

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    その他リンク: http://search.jamas.or.jp/link/ui/1997127564

  • マウスレトロウイルス感染マウスに対するグリチルリチン製剤の治療効果及び疾患進行の抑制機序

    宮路 智香子, 渡部 久実, 牧野 正彦

    Minophagen Medical Review   41 ( 5 )   292 - 300   1996年9月

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    記述言語:日本語   出版者・発行元:(株)ミノファーゲン製薬  

    マウス白血病ウイルス(LP-BM5)によるマウスAIDS(MAIDS)モデルを用い,SNMCの投与効果の評価を試みた.ウイルス感染マウスは全て発症し,感染14週迄に死亡した.SNMCを投与した感染マウスの一部に長く生存したマウスがみられたが,死亡率に有意差は認められなかった.又,これらの長期生存マウスでは,脾腫及び全身のリンパ節腫脹が抑制され,細胞表面マーカー及びCon Aに対する反応も正常であった.又,感染マウスの肝,脾,リンパ節のリンパ球をin vitroで培養すると,これらのリンパ球は自発的増殖を示したが,それらに正常マウス又はSNMC単独投与マウスの肝リンパ球を加えた時のみ,このリンパ球の増殖が抑えられた

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講演・口頭発表等

  • 長期的に繰り返したマイルドな温熱刺激が生体防御機構及び自律神経系へ与える影響について

    富山智香子, 渡邉真弓, 早川陽喜, 本間隆

    第83回日本温泉気候物理医学会総会・学術集会  2018年 

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    開催年月日: 2018年

    会議種別:口頭発表(一般)  

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  • 入浴が「美容」と「健康」におよぼす影響-顔の「色(赤み)」の定量化と静脈血中酸素飽和度との相関性

    早川陽喜, 渡邉真弓, 富山智香子

    第82回日本温泉気候物理医学会総会・学術集会  2017年 

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    開催年月日: 2017年

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  • 体温、白血球の自律神経支配、エネルギー産生への影響 新温熱刺激 ナノミストサウナーを用いて

    本間 隆, 渡邉 まゆみ, 富山 智香子, 安保 徹

    第75回日本温泉気候物理医学会総会・学術集会  2010年6月 

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    開催年月日: 2010年6月

    記述言語:日本語  

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  • 体温と白血球の自律神経支配への影響 新しい温熱刺激(ナノミストサウナ)を用いて

    渡邉 まゆみ, 安保 徹, 富山 智香子, 本間 隆, 稲田 昭弘

    第74回日本温泉気候物理医学会  2009年11月 

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    開催年月日: 2009年11月

    記述言語:日本語  

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  • ConA肝炎マウスにおける肝樹状細胞の役割

    富山(宮路) 智香子, 渡部 久実, 安保 徹

    第37回日本免疫学会総会・学術集会  2007年11月 

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    開催年月日: 2007年11月

    記述言語:日本語  

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  • ConA肝炎マウスにおける肝内樹状細胞のサブセット変化とその機能解析

    富山(宮路) 智香子, 渡部 久実, 安保 徹

    第35回日本免疫学会総会・学術集会  2005年12月 

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    開催年月日: 2005年12月

    記述言語:日本語  

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  • 生体部分肝移植の移植片生着に関与する肝内成熟樹状細胞の経時的検討

    富山 智香子, 山際 訓, 市田 隆文, 渡部 久実, 石本 結子, 佐藤 好信, 青柳 豊

    第41回日本肝臓学会総会  2005年5月 

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    開催年月日: 2005年5月

    記述言語:日本語  

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  • ConA肝炎マウス肝内樹状細胞(DC)のレクチン結合性と局在,機能との関連性

    富山(宮路) 智香子, 渡部 久実, 横山 歩美, 富山 勝博, 安保 徹

    第34回日本免疫学会総会・学術集会  2004年12月 

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    開催年月日: 2004年12月

    記述言語:日本語  

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  • マウス肝臓に存在する樹状細胞(DC)とnatural killer T(NKT)細胞のレクチン結合能の解析

    富山(宮路) 智香子, 泉 菜花子, 渡部 久実, 安保 徹

    第44回日本リンパ網内系学会学術集会・総会  2004年7月 

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    開催年月日: 2004年7月

    記述言語:日本語  

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  • NKT細胞及び樹状細胞(DC)におけるレクチン結合能の特性

    富山(宮路) 智香子, 泉 菜花子, 渡部 久実, 安保 徹

    第33回日本免疫学会総会・学術集会  2003年12月 

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    開催年月日: 2003年12月

    記述言語:日本語  

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  • 生体部分肝移植における移植肝内樹状細胞の解析

    富山 智香子, 石本 結子, 塚田 知香, 横山 恒, 宮川 亮子, 菅原 聡, 山際 諭, 楊 秀華, 渡部 久実, 佐藤 好信, 市田 隆文, 安保 徹, 朝倉 均

    第26回リバー・カンファレンス総会  2003年11月  新潟医学会

  • 生体部分肝移植における移植肝内樹状細胞の動態

    宮路 智香子, 渡部 久実, 宮川 亮子, 亀山 仁史, 佐藤 好信, 安保 徹

    第31回日本免疫学会総会・学術集会  2001年12月 

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    開催年月日: 2001年12月

    記述言語:日本語  

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  • マウス肝に存在する樹状細胞の表面抗原とその抗原提示能の解析

    宮路 智香子, 渡部 久実, 宮川 亮子, 横山 恒, 富山 勝博, 安保 徹

    第30回日本免疫学会総会・学術集会  2000年11月 

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    開催年月日: 2000年11月

    記述言語:日本語  

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  • マウス肝リンパ球の細胞傷害活性に対する漢方製剤(グリチルリチン)の作用

    宮路 智香子, 渡部 久実, 安保 徹

    第29回日本免疫学会総会・学術集会  1999年12月 

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    開催年月日: 1999年12月

    記述言語:日本語  

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  • in vitroでの胸腺外分化T細胞の分化誘導

    宮路 智香子, 渡部 久実, 関 修司, 安保 徹

    第28回日本免疫学会総会・学術集会  1998年12月 

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    開催年月日: 1998年12月

    記述言語:日本語  

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  • 肝類洞の胸腺外分化intermediateTCR細胞のIL-7に対する応答性

    宮路 智香子, 渡部 久実, 安保 徹

    日本免疫学会総会・学術集会  1993年10月 

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    開催年月日: 1993年10月

    記述言語:日本語  

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  • Relationship between dendritic cell modulation and autoimmune hepatitis exacerbation during high fat feeding.

    富山智香子, 山本秀輝, 渡部久実

    第48回日本免疫学会総会・学術集会  2019年12月 

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  • Exacerbation mechanisms of autoimmune hepatitis in the low estrogen status and its relationship with hepatic dendritic c ells.

    富山智香子, 平間拓輝, 山本秀輝, 渡部久実

    第26回マクロファージ分子細胞生物学国際シンポジウム  2019年6月 

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  • Possible factors which exacerbate autoimmune hepatitis in low-level estrogen.

    平間拓輝, 富山智香子, 渡部久実, 山本秀輝

    第47回日本免疫学会総会・学術集会  2018年12月 

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  • The effects of ovariectomy on autoimmune hepatitis and hepatic dendritic cells.

    平間拓輝, 富山智香子, 渡部久実

    第46回日本免疫学会総会・学術集会  2017年12月 

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  • The blockade of estrogen receptors on dendritic cells exacerbates autoimmune hepatitis.

    富山智香子, 渡部久実

    第45回日本免疫学会総会・学術集会  2016年12月 

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  • Estrogen inhibited liver injury in Concanavalin A-induced hepatitis mice. ―Focused on dendritic cells in the liver―

    五十島亜美, 富山智香子, 渡部久実

    第43回日本免疫学会総会・学術集会  2014年12月 

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  • concanavalin A誘導性肝炎における肝内樹状細胞と肝障害抑制との関連性について

    富山智香子, 渡部久実, 成田美和子, 高橋益廣

    第20回日本樹状細胞研究会  2010年6月 

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  • Possible role of hepatic dendritic cells in preventing liver injury induced by Concanavalin A.

    富山(宮路)智香子, 渡部久実, 渡邉真弓, 安保徹

    第38回日本免疫学会総会・学術集会  2008年12月 

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  • Adultマウス肝のLin-c-kit+細胞の性状とin vitroでのT細胞への分化

    宮路智香子, 渡部久実, 関修司, 安保徹

    第27回日本免疫学会総会・学術集会  1997年10月 

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    記述言語:日本語  

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  • Adultマウス肝に存在するLin-c-kit+細胞の解析

    宮路智香子, 渡部久実, 関修司, 安保徹

    第26回日本免疫学会総会・学術集会  1996年11月 

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  • 胸腺外分化T細胞におけるCD69抗原の発現

    宮路智香子, 渡部久実, 安保徹

    第25回日本免疫学会総会・学術集会  1995年11月 

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  • 胸腺外分化T細胞のIL-2Rβ鎖とNK1.1抗原の発現

    宮路智香子, 渡部久実, 安保徹

    第24回日本免疫学会総会・学術集会  1994年11月 

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共同研究・競争的資金等の研究

  • 脂質代謝と肝樹状細胞を組合せた自己免疫性肝炎の早期診断法の開発

    研究課題/領域番号:17K08977

    2017年4月 - 2020年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    富山 智香子, 尾関 百合子, 佐藤 英世

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    自己免疫性肝炎(autoimmune hepatitis: AIH)は、50代以降の女性に多く発症する慢性肝炎であると共に、近年、男性患者や重症患者の増加がみられるようになってきた。そのため、AIHの発症・病態進展要因には性差だけでなく複合的な因子が考えられる。そこで、我々は昨年度マウスに卵巣摘出術(ovariectomy; OVX)を行い、低エストロゲン状態がAIH肝障害とDCへ与える影響について検討を行った。その結果、OVXによりAIH肝障害は有意に増悪し、肝障害時の標的臓器である肝では、siglec-H+PDCA-1+B220+形質細胞様樹状細胞(plasamacytoid dendritic cells; pDC)の減少傾向、I-A+F4/80+通常型樹状細胞(conventional dendritic cells; cDCs)の有意な増加を認めたことを報告した。そこで、今年度も昨年に引き続き低エストロゲン状態で変化の見られたDC分画機能とDCによる刺激が影響するT細胞分画・機能について検討を行った。その結果、OVXしたマウスのAIH肝障害時の肝DCはTNF-αおよびIL-12産生量が増加した一方、IL-10産生減弱を認めた。また、肝臓のT細胞については、CD4+T細胞、CD8+T細胞共にOVXによりCD69発現が増強し、AIH肝障害時にはより加速した。さらに、血中のIFN-γ、TNF-α、およびIL-4産生量も増加した。以上のことから、AIH肝障害は低エストロゲン状態で増悪し、その免疫学的機序として1)pDCの減少と機能的減弱、2)cDCの増加とTNF-αによる直接的肝細胞障害の増強、3)活性化T細胞の増加による肝障害の増強が推察された。

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  • 女性ホルモンと肝樹状細胞の変化が自己免疫性肝炎発症へ与える影響について

    研究課題/領域番号:26460643

    2014年4月 - 2017年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    富山 智香子, 渡邉 香奈子, 渡部 久実

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    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    エストロゲンの低下する中年女性に自己免疫性肝炎は好発する。そこで、エストロゲンの増減が自己免疫性肝炎の発症及び進展にどのように影響するかについて、肝樹状細胞に焦点を当てて検討した。その結果、エストロゲンはエストロゲン受容体α鎖を介して肝形質細胞様樹状細胞のIL-10産生を増加させ自己免疫性肝障害を抑制した。一方、エストロゲン受容体阻害および閉経により抑制作用が減弱したと同時に、肝骨髄系樹状細胞が活性化し、IL-12p70およびTNFα産生が増大し肝障害増悪を誘導した。

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  • 性差に基づいた自己免疫性肝炎の発症と肝内樹状細胞との関連性について

    研究課題/領域番号:23510345

    2011年 - 2013年

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    富山 智香子, 井筒 ゆみ, 渡部 久実

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    配分額:3900000円 ( 直接経費:3000000円 、 間接経費:900000円 )

    自己免疫性肝炎は、妊娠や閉経など性ホルモンの変動で誘発されることが報告されているが、その発症機構について解明に至っていない。このことから、エストロゲンの自己応答性への影響について自己免疫性肝炎モデルを用いて樹状細胞に焦点を当てて検討した。その結果、エストロゲン投与により自己免疫性肝障害が抑制され、これらマウス肝内にCD274陽性で未熟な樹状細胞の増加を認めた。また、これら肝内樹状細胞のみにIL-10産生能の増強を認め、血清中のIL-12量が減少していた。以上から、エストロゲン暴露によって肝内に増加した抑制能を持つ樹状細胞が、自己免疫性肝障害を抑制する可能性が示唆された。

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  • 自己免疫性肝炎における肝樹状細胞に着目した早期診断とその病態解明

    研究課題/領域番号:19790394

    2007年 - 2009年

    制度名:科学研究費助成事業 若手研究(B)

    研究種目:若手研究(B)

    提供機関:日本学術振興会

    富山 智香子, 渡部 久実

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    配分額:3610000円 ( 直接経費:3100000円 、 間接経費:510000円 )

    自己免疫性肝炎の発症機序と早期特異的診断法の基礎的研究のために、モデルマウスの肝内樹状細胞の動態について検討を行った。その結果、モデルマウスの肝では活性化骨髄系樹状細胞が増加し、多量な炎症性サイトカイン産生を認めた。また、この肝障害を制御するには肝臓内の形質細胞様樹状細胞が部分的に必要である事が明らかとなった。さらに肝障害抑制には調節性T細胞も一部関連する可能性があり、血中においてTh2サイトカイン産生を認めた。このことから、自己免疫性肝炎における肝障害のコントロールには肝臓内の形質細胞様樹状細胞と制御性T細胞の連携が必要であり、これらをもとにした自己免疫性肝炎の早期発見及び新たな治療方法への基盤作成の可能性が示唆された。

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  • 生体肝移植における樹状細胞とNKT細胞の動態による拒絶発見とその制御機講の解析

    研究課題/領域番号:15790275

    2003年 - 2004年

    制度名:科学研究費助成事業 若手研究(B)

    研究種目:若手研究(B)

    提供機関:日本学術振興会

    富山 智香子

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    配分額:3500000円 ( 直接経費:3500000円 )

    本研究課題において、得られた成果を以下に示す。
    1.ヒト生体部分肝移植での移植片拒絶と移植肝内樹状細胞とNKT細胞との関連性
    ヒト正常肝内樹状細胞(dendritic cells : DC)は表面マーカー上成熟型、逆に末梢血内DCは未熟型であることを前年度に報告している。また、生体肝移植におけるトレランス誘導には移植肝内CD28^+CD56^+T細胞の減少とdonor type CD56^+T細胞のキメリズムの長期形成が重要であることを我々のグループは報告している。今回、肝移植におけるトレランス誘導と肝および末梢血の樹状細胞との関連性を調べるために、生着している症例と拒絶反応を起こした症例とでその違いについて検討を行った。その結果、移植肝内では拒絶反応を起こした症例は生着している症例と比べ、成熟型DCの割合の減少を認めた。しかし、末梢血ではDC全体の割合が増加傾向にあるものの、正常と同様に未熟型DCが多かった。このことから、成熟型である肝DCがトレランスを誘導し、移植片生着に重要な働きをしていることが示唆された。またこのことから、移植肝内のDCの性状を調べることにより、拒絶反応の早期発見の可能性も示唆された。
    2.マウス肝樹状細胞の機能解析
    マウス肝DCは脾と比べ、表面マーカー的、および機能的にみて未熟型が多く存在すると考えられることを前年度報告した。今回は、機能解析としてDCの自然免疫で働いている重要な分子であるToll-like receptor(TLR)に着目し、またDCとT,B細胞間のinteractionに糖鎖が関係していることが近年報告され始めてきているため、この点について解析を行った。その結果、肝DCは脾と比べ、TLR2およびTLR3の低発現という特徴が見られた。糖鎖については、ジ-N-アセチルキトビオース、およびN-アセチルガラクトサミンの高結合性が見られた。

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  • 脂質異常と肝内樹状細胞を標的とした自己免疫性肝炎の発症および病態の解明

    研究課題/領域番号:22K07958

    2022年4月 - 2025年3月

    制度名:科学研究費助成事業

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    富山 智香子, 尾関 百合子, 佐藤 英世

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

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  • 繰り返すマイルドな温熱刺激の健康増進効果における新たな免疫応答機序の探索

    2021年7月 - 2022年6月

    研究種目:試験研究費助成

    提供機関:公益財団法人 内田エネルギー科学振興財団

    富山智香子

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    担当区分:研究代表者 

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  • 生体の免疫応答を高めるための環境条件と温熱刺激条件の追究

    2020年7月 - 2021年6月

    研究種目:試験研究費助成

    提供機関:公益財団法人 内田エネルギー科学振興財団

    富山智香子

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    担当区分:研究代表者 

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  • 統合医療による「冷え」の解明とその予防

    研究課題/領域番号:19K10727

    2019年4月 - 2022年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    渡邉 真弓, 王 財源, 富山 智香子, 武田 時昌

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    今年度もCovid-19感染拡大防止が必用であり蜜を回避するため、本研究で予定していたヒト対象の実験を行うことができなかった。しかし、「冷え」は個人の主観的な感覚であり、数値的に客観的所見を得ることは困難である。本来はこの「冷え」にについて、静脈血中血液ガスや免疫細胞を測定する実験により特徴を客観的に評価し、かつ、体温低下といわれる「冷え」脱却のため温熱刺激を与えることで「冷え」解決の方法を模索する予定であった。
    そこで、今回は、客観的所見を求める実験を実施することはできなかったので、主観的に「冷え」有の人の、背景を探索した。昨年度「大寒」の日に全国1000名の女性(20-59歳)を対象に「冷え」について、多角的なアンケート、および、Covid-19拡大に伴い急速に普及した非接触型体温計を用いた体温測定を実施して、情報を収集した。このデータをSPSS(統計解析ソフト)を用いて、Chi-test、および、multivariate logistic regression解析、そして、体温について、「冷え」無群と「冷え」有群の2群検定を行った。
    その結果、「冷え」の背景にはストレス(特に心理的)による、血流低下に伴う体温低下の可能性など、「冷え」の背景、そして、原因となる要因を得ることができた。これらの結果をまとめ、国民の多くが悩む「冷え」から脱却する仮説を構築した。これらの成果を英文論文にまとめ、現在、海外OA型雑誌に投稿準備中である。また、これらの成果を複数の学会において発表して広くこの成果を「冷え」に悩む人々に知ってもらう予定である。

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  • 結核ワクチン開発を指向した抗酸菌特有の翻訳後修飾付加ポリペプチドの抗原性検証

    研究課題/領域番号:19K07536

    2019年4月 - 2022年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    尾関 百合子, 富山 智香子

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

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  • 原発被災市町村復興の担い手となる壮年期男性への生活と健康に関する支援方法の構築

    研究課題/領域番号:18K02058

    2018年4月 - 2022年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    岩佐 有華, 齋藤 智子, 富山 智香子, 西方 真弓

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    本年度は、原発災害により被災し長期の避難生活を送る壮年期男性(以下、被災群)と被災していない壮年期男性(以下、非被災群)の睡眠とストレスを比較することを目的に、非被災群10名の睡眠とストレスに関するデータ収集を行い、その結果を分析した。
    客観的睡眠状態はActigraphを、主観的睡眠状態はピッツバーグ睡眠質問票(以下,PSQI)を用いてデータ収集を行った。Actigrapでは、Sleep Minutes(睡眠時間),Sleep Efficiency(睡眠効率),Sleep Latency(入眠潜時),Wake after Sleep Onset(中途覚醒時間)の測定を行った。
    主観的ストレス状態は精神健康調査票(以下,GHQ28)を,客観的ストレス状態は唾液ストレスバイオマーカー(α-Amylase,Cortisol,Chromogranin A, s-IgA)を用いてデータ収集を行った。
    今回収集した非被災群のデータを、以前に収集した被災群のデータ(仮設住宅居住時及び復興住宅居住時)と比較するためにMann-Whitney の U検定を用いて分析した(p<0.05)。
    その結果、非被災群と復興住宅居住時の被災群では、睡眠とストレスに有意差は認められなかった。一方で、非被災群と仮設住宅居住時の被災群では、PSQI総得点(p=0.039)及びPSQI下位尺度睡眠時間(p=0.006)及びSleep Latency(p=0.034)において有意差が認められた。
    これらのことから、原発災害により長期の避難生活を送る壮年期男性の仮設住宅居住時の睡眠は被災し避難していない一般の壮年期男性と比較して、有意に悪いことが明らかになった。

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  • 精神機能と免疫機能の相関研究

    研究課題/領域番号:16K01786

    2016年4月 - 2020年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    七里 佳代, 富山 智香子, 渡邉 真弓

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    本研究の平成30年度の研究実績の概要を報告する。
    平成29年度報告書での「今後の推進方策」に記したとおり、「精神的健常群」の精神医学的データを収集・解析して学会発表した(Efficiency of defensive functioning scale:Correlation to Beck's Depression Inventory,13th World congress on Healthcare & Technolpgies,Dublin,Ireland,2018.6.14-15)。本年度は続編を発表予定である(14th World congress on Healthcare & Technolpgies,London,UK,2019.7.22-23)。
    平成28年度中に得られていた「精神症状発現群」の生体情報検査データの診断別解析の結果では、自閉スペクトラム症群と適応障害群について、末梢体表温度が低く、末梢の血流循環が低い傾向が示された。自閉スペクトラム症群では顆粒球、NK細胞、NKT細胞が関わる自然免疫増強傾向がうかがえた。自然免疫増強傾向はストレスホルモン反応性との関連が報告されているが、自閉スペクトラム症群ではストレスホルモンであるコルチゾールとアドレナリンは低下しており、ストレスホルモン反応性とは関連性が低いと考えられた。一方、セロトニンとNk細胞の関連性についてはうつ病者におけるSSRI投与後のNK細胞活性の上昇が報告されており、自閉スペクトラム症群におけるNK細胞の増加傾向にセロトニンが関与している可能性が示唆された。
    また「精神症状発現群」の伝統医学的検査データ(舌診)の分析結果では、自閉スペクトラム症群の舌像は様々であった。適応障害群では「点刺」が多い傾向が認められ、精神的ストレスが関係して発生するとされる中医理論に合致していた。

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  • 結核菌の新しいヒト免疫抑制機構の解明とその解除による新規制御法の開発

    研究課題/領域番号:16K08774

    2016年4月 - 2019年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    尾関 百合子, 富山 智香子

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    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    結核は、最大級の細菌感染症であり、結核菌はその起因菌である。結核菌は一旦感染が成立するとヒト体内から排除されることなく、無症候感染というかたちで潜伏する(潜在性結核)。無症候感染者は人類の1/3に及び、年率約1%で発症するが、HIV感染、糖尿病など免疫抑制を伴う負荷は、発症リスクを上昇させる。このことは、宿主免疫応答が結核の発症と潜在化に多大に関与することを示している。本研究では結核菌の宿主に対する免疫抑制機構の一端を明らかにするとともに、それを解除する方法を見いだし、ワクチン開発の可能性を示した。

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  • 原発災害により超長期に応急仮設住宅に避難する被災者の特徴と支援プログラムの構築

    研究課題/領域番号:15K11929

    2015年4月 - 2018年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    岩佐 有華, 青木 萩子, 齋藤 智子, 西方 真弓, 村松 芳幸, 富山 智香子

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    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    東日本大震災に関連した福島第一原子力発電所事故による長期の避難生活が,住民の睡眠や精神健康に影響することが明らかになっており,心身への影響が懸念されている.そこで今回,長期に避難生活を送る壮年期男性の睡眠とストレスについて,仮設住宅居住時と復興住宅居住時でのそれぞれの実際を明らかにすることを目的に研究を行った.
    その結果,応急仮設住宅居住時と復興住宅居住時の比較において,客観的睡眠と客観的ストレスに有意な変化は認められなかったが,主観的睡眠と主観的ストレスは復興住宅居後,有意に悪化していることが明らかになった.

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  • 応急仮設住宅居住高齢者のストレス応答反応,環境,眠りの関連と包括的睡眠ケアの構築

    研究課題/領域番号:24593191

    2012年4月 - 2016年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    齋藤 君枝, 青木 萩子, 藤原 直士, 富山 智香子, 岩佐 有華

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    配分額:5460000円 ( 直接経費:4200000円 、 間接経費:1260000円 )

    東日本大震災後、応急仮設住宅居住に居住する高齢被災者に対し、睡眠障害とその関連要因を検討した。睡眠の悪化は体調、受診状況が有意に関連していた。また、抑うつの有無と睡眠の質、睡眠困難、体重の減少が関連していた。生活環境では居室、風呂、トイレ、買い物の不便が睡眠に影響していた。避難に伴う心身の不調や疾患、生活環境が睡眠の悪化に影響を及ぼすと考えられた。包括的睡眠ケアには、早期からの睡眠障害のスクリーニング、情報収集の継続、ハイリスク者に対する定期的なアウトリーチ、多職種による連携介入が必要である。

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  • 臓器移植における再生間葉系肝幹細胞門脈内投与による新たな免疫寛容誘導法の確立

    研究課題/領域番号:21390356

    2009年 - 2012年

    制度名:科学研究費助成事業 基盤研究(B)

    研究種目:基盤研究(B)

    提供機関:日本学術振興会

    佐藤 好信, 安保 徹, 松田 康伸, 富山 智香子

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    配分額:17420000円 ( 直接経費:13400000円 、 間接経費:4020000円 )

    本研究の全体構想は、これまでの臨床研究の成果を基に、臨床生体臓器移植におけるOperational Toleranceを誘導するメカニズムを解析しさらに肝幹細胞を中心とした再生医療を応用したスーパードナー抗原による新たな方法論を確立することである。基礎的検討としては、ヒト肝組織特に障害肝のductularreactionの存在する領域にCD133+NCAM+ human hepatic stem/progenitor細胞の存在が確認された。特に障害の程度が高い程、その存在は明らかであった。しかし正常肝組織での肝幹細胞の確認はできなかった。やはり肝幹細胞は肝に何らかの障害がもたらされて初めて誘導されるものと考えられた。ドナー抗原の門脈内投与の免疫学的検討においては、免疫寛容誘導症例でFoxP3^+/CD4^+CD25^+調節性T細胞の割合が有意に増加しており、免疫寛容に関与していることが判明した。また肝障害度(MELDスコアー)別に移植前後の免疫学的検討を行ったが、MELDスコアー20以上の症例では、調節性T細胞が有意となっており肝障害度別に免疫状態を把握する事により移植後免疫抑制剤の使用方法を調整できることが判明した。

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  • マラリア原虫感染におけるNKT-肝樹状細胞による免疫抑制機構

    研究課題/領域番号:16017290

    2004年 - 2005年

    制度名:科学研究費助成事業 特定領域研究

    研究種目:特定領域研究

    提供機関:日本学術振興会

    渡部 久実, 富山 智香子

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    配分額:7000000円 ( 直接経費:7000000円 )

    【目的】マラリア感染における宿主の免疫抑制現象、特にT細胞応答の抑制はマウスモデルやマラリア患者の解析からよく知られていた。その原因として、regulatory T細胞の誘導、helper T細胞のアポトーシスや抗原提示細胞の機能不全などが報告されているが、近年樹状細胞(DC)の成熟阻害や機能変化が注目されてきている。本研究では、ネズミマラリア原虫P.yoelli17XNL(非致死株)を用い、感染防御能の増強とは相反する現象である免疫抑制機構を肝DCの動態から解明し、ワクチントライアルへの基礎的知見を得ることを目的とした。
    【成果と考察】正常マウス肝ではplasmacytoid DC(pDC)抗原(PDCA-1)を強発現するCD11c^<low>I-A^-DCが優位を占め、CpG刺激によりIFN-α産生が強く誘導されることから、pDCであることが確認できた。脾ではCD205陽性のCD11c^<high>I-A^+DC(myeloid DC:mDC)が優位を占める。感染急性期(Day7)において、肝及び脾のCD11c^<low>I-A^-B220^+DCが著しく増加し、CD86の強発現が認められたが、PDCA-1抗原の発現は低下しIFN-αの産生も低下した。一方、肝及び脾のCD11c^<high>I-A^+DCは減少した。このようなDCサブセットの表面抗原変化は、血中から原虫が排除される感染後期(Day25以降)から回復してきた。致死株感染マウスでは、非致死株感染と同様にCD11c^<low>I-A^-DCでのPDCA-1抗原の発現低下だけでなく両DCサブセットでのB220とCD86抗原の発現も低下し、両者の間に明らかな差異が認められた。CpG刺激による炎症性サイトカインであるIL-12、IL-10やTNFαの産生能は、感染の有無にかかわらず肝臓及び脾臓のCD11c^<high>I-A^+DCで高く、CD11c^<low>I-A^-DCではいずれも低値を示した。これらの結果から、マラリア原虫感染に伴ない肝DCの性状が変化し、また、原虫株による違いも見られることが明らかとなった。すなわち、肝のmDC分画は感染によりIL-12やTNFα産生を誘導することにより感染防御を担うNKT細胞の活性化に関与し、一方、pDC分画ではIFN-α産生能の低下に伴いウイルス感染防御能等が低下するものと考えられた。

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担当経験のある授業科目(researchmap)

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  • 臓器移植検査科学

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  • 保健学特定研究

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  • 医学と医療の歴史

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  • 免疫検査科学実習

    機関名:新潟大学

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  • 免疫検査学演習

    機関名:新潟大学

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  • 卒業研究

    機関名:新潟大学

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  • 生活習慣と健康

    機関名:新潟大学

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  • 医学検査管理総論

    機関名:新潟大学

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  • 臨床生体情報検査科学論

    機関名:新潟大学

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  • リサーチ・メソッズ・ベーシック

    機関名:新潟大学

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  • 基礎免疫学

    機関名:新潟大学

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  • 免疫病態検査学実習

    機関名:新潟大学

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    機関名:新潟大学

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    機関名:新潟大学

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    2017年
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    機関名:新潟大学

  • 臨床検査実習

    2016年
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    機関名:新潟大学

  • 医学検査管理総論

    2016年
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    機関名:新潟大学

  • リサーチ・メソッズ・ベーシック

    2015年
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    2021年
    機関名:新潟大学

  • リサーチ・メソッズ・アドバンスト

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    2021年
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  • 医学と医療の歴史

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  • 保健学特別研究(検査技術科学)

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    2018年
    機関名:新潟大学

  • 免疫・血液病態検査学特講

    2014年
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    2016年
    機関名:新潟大学

  • 免疫・血液病態検査学特講演習

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  • 医用工学概論

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    機関名:新潟大学

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    2012年
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    機関名:新潟大学

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