Updated on 2024/10/01

写真a

 
HARUSATO Akihito
 
Organization
Graduate School of Medicine Center for Research of Laboratory Animals and Medical Research Engineering Division for Advanced Medical Research Designated lecturer
Title
Designated lecturer

Research Interests 9

  1. Food Allergy

  2. Epidemiology

  3. 環境因子

  4. Nano/Microplastic

  5. T cell

  6. Microbiome

  7. Exposome

  8. Cytokine

  9. Antigen Presenting Cells

Research Areas 4

  1. Life Science / Hygiene and public health (laboratory)

  2. Life Science / Gastroenterology

  3. Life Science / Nutrition science and health science

  4. Life Science / Immunology  / Mucosal Immunlogy

Research History 13

  1. Nagoya University

    2024.5

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    Country:Japan

  2. Kyoto Prefectural University of Medicine   Molecular Gastroenterology and Hepatology   Assistant Professor

    2023.4 - 2024.4

  3. 京都府健康福祉部

    2021.4 - 2024.4

  4. Kyoto Prefectural University of Medicine   Assistant Professor

    2021.4 - 2023.3

  5. Kyoto Prefectural University of Medicine   Assistant Professor

    2017.4 - 2021.3

  6. Georgia State University

    2014.4 - 2017.3

  7. RIKEN   RIKEN Center for Integrative Medical Sciences

    2012.9 - 2014.3

  8. 八幡中央病院   消化器内科   医師

    2011.4 - 2012.8

  9. Kyoto Prefectural University of Medicine

    2007.4 - 2011.3

  10. 朝日大学村上記念病院   消化器内科

    2006.4 - 2008.3

  11. National Hospital Organization

    2005.4 - 2006.3

  12. 公立山城病院(山城総合医療センター)   内科   医員

    2004.4 - 2005.3

  13. Kyoto Prefectural University of Medicine

    2002.4 - 2004.3

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Education 2

  1. Kyoto Prefectural University of Medicine   Graduate School of Medical Science

    - 2011.3

  2. Kyoto Prefectural University of Medicine

    - 2002.3

Professional Memberships 5

  1. Japan Gastroenterological Endoscopy Society

  2. 日本衛生学会

  3. JAPANESE SOCIETY OF GASTROENTEROLOGY

  4. THE JAPANESE SOCIETY FOR IMMUNOLOGY

  5. Society for Mucosal Immunology

Committee Memberships 3

  1. The Japanese Society of Gastroenterology   Councilor  

    2024   

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    Committee type:Academic society

  2. 京都府市町村議会議員公務災害補償等組合   委員  

    2021   

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    Committee type:Municipal

  3. 京都府医師会   感染症対策委員会 委員  

    2021   

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    Committee type:Academic society

Awards 5

  1. Family Support Award

    2023   Cell Symposia: Infection Biology in the Age of Microbiome  

    Akihito Harusato

  2. Young Investigator Award

    2017   Society for Mucosal Immunology  

    Akihito Harusato

  3. Research Fellowship Award

    2016   Crohn's and Colitis Foundation of America   Il-36 mediated regulation of acute and chronic intestinal inflammation

    Akihito Harusato

  4. Best Paper Award

    2011   第20回消化器とフリーラジカル研究会  

  5. Travel Award

    2010   The 6th International Congress on Heme Oxygenase, Miami, USA  

    Akihito Harusato

 

Papers 48

  1. Short- and long-term outcomes of endoscopic submucosal dissection and laparoscopic and endoscopic cooperative surgery for superficial non-ampullary duodenal epithelial tumors. Reviewed International journal

    Mayuko Seya, Osamu Dohi, Naoto Iwai, Tomoko Ochiai, Hiroki Mukai, Katsuma Yamauchi, Hayato Fukui, Hajime Miyazaki, Takeshi Yasuda, Tsugitaka Ishida, Toshifumi Doi, Ryohei Hirose, Ken Inoue, Akihito Harusato, Naohisa Yoshida, Kazuhiko Uchiyama, Takeshi Ishikawa, Tomohisa Takagi, Yukiko Morinaga, Takeshi Kubota, Hideyuki Konishi, Yoshito Itoh

    Surgical endoscopy     2024.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND AND AIMS: This retrospective study aimed to compare the short- and long-term outcomes of endoscopic submucosal dissection and laparoscopic and endoscopic cooperative surgery in patients with superficial non-ampullary duodenal epithelial tumors. PATIENTS AND METHODS: We investigated consecutive patients with SNADETs > 10 mm in size who underwent ESD (ESD group) or LECS (LECS group) between January 2015 and March 2021. The data was used to analyze the clinical course, management, survival status, and recurrence between the two groups. RESULTS: A total of 113 patients (100 and 13 in the ESD and LECS groups, respectively) were investigated. The rates of en bloc resection and curative resection were 100% vs. 100% and 93.0% vs. 77.0% in the ESD and LECS groups, respectively, with no significant difference. The ESD group had shorter resection and suturing times than the LECS group, but there were no significant difference after propensity score matching. There were also no differences in the rates of postoperative adverse event (7.0% vs. 23.1%; P = 0.161). The 3-year overall survival (OS) rate was high in both the ESD and LECS groups (97.6% vs. 100%; P = 0.334). One patient in the ESD group experienced recurrence due to liver metastasis; however, no deaths related to SNADETs were observed. CONCLUSION: ESD and LECS are both acceptable treatments for SNADETs in terms of a high OS rate and a low long-term recurrence rate, thereby achieving a comparable high rate of curative resection. Further studies are necessary to compare the outcomes of ESD and LECS for SNADETs once both techniques are developed further.

    DOI: 10.1007/s00464-023-10666-x

    PubMed

  2. Editorial: Impact of gut ecosystem in health and diseases: microbiome, mucosal barrier and cytokine milieu Reviewed

    Akihito Harusato, Hirohito Abo, Yoshito Itoh, Timothy L. Denning

    Frontiers in Microbiology   Vol. 14   2024.1

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    Publishing type:Research paper (scientific journal)   Publisher:Frontiers Media SA  

    DOI: 10.3389/fmicb.2023.1345703

  3. Efficacy of Glycicumarin and Isoliquiritigenin in Suppressing Colonic Peristalsis in Both an Animal Model and a Clinical Trial. Reviewed

    Reo Kobayashi, Ken Inoue, Satoshi Sugino, Ryohei Hirose, Toshifumi Doi, Akihito Harusato, Osamu Dohi, Naohisa Yoshida, Kazuhiko Uchiyama, Takeshi Ishikawa, Tomohisa Takagi, Hideyuki Konishi, Yasuko Hirai, Katsura Mizushima, Yuji Naito, Yoshito Itoh

    Biological & pharmaceutical bulletin   Vol. 47 ( 2 ) page: 373 - 382   2024

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    Language:English   Publishing type:Research paper (scientific journal)  

    Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) show excessive peristalsis, and antispasmodic agents may be useful therapeutic agents. There are few reports on the use of Kampo medicines for the treatment of IBS-D. Shakuyakukanzoto (SKT) is a Kampo medicine that is effective against abdominal pain. We examined the relationship between SKT and intestinal peristalsis in an animal model and a prospective study. In the animal model, SKT and its components were administered from the serosal side of the colon and colonic peristalsis was evaluated using intraluminal pressure and spatiotemporal mapping before and after the administration of SKT and its components. In this clinical trial, we used abdominal ultrasonography (US) to obtain long-axis images of the sigmoid colon of 11 patients. The frequency of intestinal peristalsis was measured using US in five patients with SKT and six patients without medication after the ingestion of a test meal. The primary outcome was the frequency of peristalsis. The Clinical Trial Registry Website (Trial No. UMIN-CTR; UMIN000051547). In the animal model, peony did not suppress peristalsis frequency, but SKT (p = 0.005) and glycyrrhiza (p = 0.001) significantly suppressed peristalsis frequency compared with saline and peony. Among the glycyrrhiza components, glycycoumarin and isoliquiritigenin suppressed the peristalsis frequency compared to dimethyl sulfoxide (control) (p = 0.001, 0.01, respectively). In a clinical trial, peristalsis was significantly suppressed after oral administration in patients taking SKT (p = 0.03). Administration of SKT was found to inhibit colonic peristalsis, with glycicumarin and isoliquiritigenin being particularly relevant among its components.

    DOI: 10.1248/bpb.b23-00680

    PubMed

  4. Protocol for acquiring samples to assess the impact of microplastics on immune microenvironments in the mouse intestine Reviewed International journal

    Akihito Harusato, Wooseok Seo, Hirohito Abo, Yoshitaka Nakanishi, Hiroyoshi Nishikawa, Yoshito Itoh

    STAR Protocols   Vol. 4 ( 4 ) page: 102648 - 102648   2023.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    Environmental nano- and microplastics (NMPs) pose serious environmental issues, yet there is no established technique to assess their impact on health through oral ingestion. Here, we present a protocol to assess the impact of NMPs in the intestinal immune microenvironments by employing chronic exposure to NMPs in a mouse model. We describe steps for administration of NMPs, feces and tissue collection, and colonic gut digestion. We then detail procedures for isolation of intestinal immune cells and RNA isolation. For complete details on the use and execution of this protocol, please refer to Harusato et al.1.

    DOI: 10.1016/j.xpro.2023.102648

    Web of Science

    PubMed

  5. N-acetylglucosamine-6-O-sulfation on intestinal mucins prevents obesity and intestinal inflammation by regulating gut microbiota Reviewed International journal

    Hirohito Abo, Aoi Muraki, Akihito Harusato, Tetsuya Imura, Maki Suzuki, Kohta Takahashi, Timothy L. Denning, Hiroto Kawashima

    JCI Insight   Vol. 8 ( 16 )   2023.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:American Society for Clinical Investigation  

    Intestinal mucins play an essential role in the defense against bacterial invasion and the maintenance of gut microbiota, which is instrumental in the regulation of host immune systems; hence, its dysregulation is a hallmark of metabolic disease and intestinal inflammation. However, the mechanism by which intestinal mucins control the gut microbiota as well as disease phenotypes remains nebulous. Herein, we report that N-acetylglucosamine (GlcNAc)-6-O sulfation of O-glycans on intestinal mucins performs a protective role against obesity and intestinal inflammation. Chst4-/- mice, lacking GlcNAc-6-O sulfation of the mucin O-glycans, showed significant weight gain and increased susceptibility to dextran sodium sulfate-induced colitis as well as colitis-associated cancer accompanied by significantly reduced immunoglobulin A (IgA) production caused by an impaired T follicular helper cell-mediated IgA response. Interestingly, the protective effects of GlcNAc-6-O sulfation against obesity and intestinal inflammation depend on the gut microbiota, evidenced by the modulation of the gut microbiota by cohousing or microbiota transplantation reversing disease phenotypes and IgA production. Collectively, our findings provide insight into the significance of host glycosylation, more specifically GlcNAc-6-O sulfation on intestinal mucins, in protecting against obesity and intestinal inflammation via regulation of the gut microbiota.

    DOI: 10.1172/jci.insight.165944

    PubMed

  6. Impact of particulate microplastics generated from polyethylene terephthalate on gut pathology and immune microenvironments. Reviewed International journal

    Akihito Harusato, Wooseok Seo, Hirohito Abo, Yoshitaka Nakanishi, Hiroyoshi Nishikawa, Yoshito Itoh

    iScience   Vol. 26 ( 4 ) page: 106474 - 106474   2023.4

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    Language:English   Publishing type:Research paper (scientific journal)  

    Environmental microplastics have emerged as a critical issue in maintaining the planetary ecosystem. In this study, we generated particulate microplastics from polyethylene terephthalate (PM-PET) and investigated their impact in the gut by using mouse models and implementing histological examinations, as well as multi-omics analysis for colonic immune cells and microbiota. As a result, histological approaches showed that chronic and physiological low dose exposure of PM-PET did not affect intestinal pathology and mucin barriers, respectively. Moreover, immunohistochemical analysis demonstrated that the numbers of T cells, B cells, macrophages, and granulocytes were not affected by the exposure to PM-PET. However, RNA-seq analysis revealed that PM-PET had a substantial impact on the transcriptome in gut immune cells and their metabolisms, while 16s rRNA metagenomic analysis showed that the composition of microbiota was modestly affected. These results suggest an unexpected role played by the PM-PET in affecting gut immune homeostasis without detectable inflammation.

    DOI: 10.1016/j.isci.2023.106474

    Web of Science

    PubMed

  7. [A case report:the progress of fascioliasis from hepatic phase to biliary phase]. Reviewed

    Fumiya Okano, Akihito Harusato, Bunta Tokuda, Hiroyuki Taketani, Hiroshi Ishiba, Akifumi Fukui, Tatsushi Omatsu, Tetsuya Okayama, Osamu Satoh, Tetsuya Imura, Mika Okita, Kazuhiro Katada, Yoshito Itoh

    Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology   Vol. 120 ( 3 ) page: 269 - 275   2023

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    Language:Japanese  

    This is a case report of fascioliasis that progressed from the hepatic to the biliary phases over 2 years. A woman in her late 60s ate Zingiber mioga from the field, which was followed by abdominal pain that occurred 1 month later. Although CT and MRI studies revealed an increase in blood eosinophils as well as multiple hepatic nodules, they vanished quickly. After 2 years, an MRCP study revealed multiple flat lesions, which were diagnosed as adult fascioliasis. Definitive diagnosis was provided by enzyme-labeled antibody method using fasciola-specific antigen. Triclabendazole was administered once to complete the treatment.

    DOI: 10.11405/nisshoshi.120.269

    PubMed

    J-GLOBAL

  8. Dietary Emulsifiers Exacerbate Food Allergy and Colonic Type 2 Immune Response through Microbiota Modulation Reviewed

    Akihito Harusato, Benoit Chassaing, Charlène J. G. Dauriat, Chihiro Ushiroda, Wooseok Seo, Yoshito Itoh

    Nutrients   Vol. 14 ( 23 ) page: 4983 - 4983   2022.11

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    Publishing type:Research paper (scientific journal)   Publisher:MDPI AG  

    The significant increase in food allergy incidence is correlated with dietary changes in modernized countries. Here, we investigated the impact of dietary emulsifiers on food allergy by employing an experimental murine model. Mice were exposed to drinking water containing 1.0% carboxymethylcellulose (CMC) or Polysorbate-80 (P80) for 12 weeks, a treatment that was previously demonstrated to induce significant alterations in microbiota composition and function leading to chronic intestinal inflammation and metabolic abnormalities. Subsequently, the ovalbumin food allergy model was applied and characterized. As a result, we observed that dietary emulsifiers, especially P80, significantly exacerbated food allergy symptoms, with increased OVA-specific IgE induction and accelerated type 2 cytokine expressions, such as IL-4, IL-5, and IL-13, in the colon. Administration of an antibiotic regimen completely reversed the emulsifier-induced exacerbated susceptibility to food allergy, suggesting a critical role played by the intestinal microbiota in food allergy and type 2 immune responses.

    DOI: 10.3390/nu14234983

    Web of Science

    PubMed

  9. Lycopene intake induces colonic regulatory T cells in mice and suppresses food allergy symptoms. Reviewed International journal

    Chihiro Ushiroda, Tomohisa Takagi, Nobuo Fuke, Katsura Mizushima, Yasuko Hirai, Yasuki Higashimura, Akihito Harusato, Kazuhiro Kamada, Kazuhiko Uchiyama, Takeshi Ishikawa, Koichi Aizawa, Hiroyuki Suganuma, Yoshito Itoh, Yuji Naito

    Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology   Vol. 33 ( 1 ) page: e13691   2022.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Food allergy (FA) is a common disease in children; thus, a high level of safety is required for its prevention and treatment. Colonic regulatory T cells (Tregs) have been suggested to attenuate FA. We investigated the Treg-inducing ability and anti-FA effects of carotenoids, a pigment contained in vegetables and fruits. METHODS: C57BL/6N mice were fed a diet containing 0.01% (w/w) of lycopene, β-carotene, astaxanthin or lutein for 4 weeks, and the population of colonic Tregs was assessed. Subsequently, to evaluate the Treg-inducing ability of lycopene, splenic naïve CD4+ T cells from BALB/c mice were cultured with anti-CD3/CD28 antibody, TGF-β and lycopene, and the frequencies of Tregs were examined. The effect of 0.1% (w/w) lycopene containing diet on FA was investigated in OVA-induced FA model BALB/c mice. RESULTS: In screening, only lycopene significantly increased the frequency and number of colonic Tregs. Lycopene also increased Treg differentiation in splenic naïve CD4+ T cells. In FA mice, lycopene feeding significantly increased the number of colonic Tregs and attenuated allergic symptoms. The expression levels of IL-4, IL-9 and IL-13 mRNA in colonic mucosa were also significantly reduced by lycopene. IL-9 is known to induce proliferation of mast cells, and we found that lycopene feeding significantly reduced the number of mast cells in the colonic mucosa of FA mice. CONCLUSION: Our results suggest that lycopene, a carotenoid present in many common foods on the market, may have the potential to induce colonic Tregs and suppress FA symptoms.

    DOI: 10.1111/pai.13691

    PubMed

  10. Establishment and role of inpatient waiting station for COVID-19 patients Reviewed

    石井亘, 高階謙一郎, 山口了吾, 春里暁人, 中川正法

    日本臨床救急医学会雑誌   Vol. 25 ( 1 )   2022

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  11. A Cre-driven allele-conditioning line to interrogate CD4+ conventional T cells. Reviewed International journal

    Lawrence P Andrews, Kate M Vignali, Andrea L Szymczak-Workman, Amanda R Burton, Erin A Brunazzi, Shin Foong Ngiow, Akihito Harusato, Arlene H Sharpe, E John Wherry, Ichiro Taniuchi, Creg J Workman, Dario A A Vignali

    Immunity   Vol. 54 ( 10 ) page: 2209 - 2217   2021.10

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    CD4+ T cells share common developmental pathways with CD8+ T cells, and upon maturation, CD4+ T conventional T (Tconv) cells lack phenotypic markers that distinguish these cells from FoxP3+ T regulatory cells. We developed a tamoxifen-inducible ThPOKCreERT2.hCD2 line with Frt sites inserted on either side of the CreERT2-hCD2 cassette, and a Foxp3Ametrine-FlpO strain, expressing Ametrine and FlpO in Foxp3+ cells. Breeding these mice resulted in a CD4conviCreERT2-hCD2 line that allows for the specific manipulation of a gene in CD4+ Tconv cells. As FlpO removes the CreERT2-hCD2 cassette, CD4+ Treg cells are spared from Cre activity, which we refer to as allele conditioning. Comparison with an E8IiCreERT2.GFP mouse that enables inducible targeting of CD8+ T cells, and deletion of two inhibitory receptors, PD-1 and LAG-3, in a melanoma model, support the fidelity of these lines. These engineered mouse strains present a resource for the temporal manipulation of genes in CD4+ T cells and CD4+ Tconv cells.

    DOI: 10.1016/j.immuni.2021.08.029

    PubMed

  12. A case of circumferential duodenal ulcer due to low-dose aspirin Reviewed

    岡野史弥, 春里暁人, 崔哲暢, 竹谷祐栄, 福居顕文, 岡山哲也, 堅田和弘, 伊藤義人

    京都府立医科大学附属北部医療センター誌   Vol. 7 ( 1 )   2021

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  13. The Crosstalk of Intestinal Immune Cells Reviewed

    春里暁人, 伊藤義人

    京都府立医科大学雑誌   Vol. 130 ( 4 )   2021

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  14. Erythroid differentiation regulator-1 induced by microbiota in early life drives intestinal stem cell proliferation and regeneration Reviewed International journal

    Hirohito Abo, Benoit Chassaing, Akihito Harusato, Miguel Quiros, Jennifer C. Brazil, Vu L. Ngo, Emilie Viennois, Didier Merlin, Andrew T. Gewirtz, Asma Nusrat, Timothy L. Denning

    Nature Communications   Vol. 11 ( 1 ) page: 513 - 513   2020.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Gut microbiota and their metabolites are instrumental in regulating intestinal homeostasis. However, early-life microbiota associated influences on intestinal development remain incompletely understood. Here we demonstrate that co-housing of germ-free (GF) mice with specific-pathogen free (SPF) mice at weaning (exGF) results in altered intestinal gene expression. Our results reveal that one highly differentially expressed gene, erythroid differentiation regulator-1 (Erdr1), is induced during development in SPF but not GF or exGF mice and localizes to Lgr5+ stem cells and transit amplifying (TA) cells. Erdr1 functions to induce Wnt signaling in epithelial cells, increase Lgr5+ stem cell expansion, and promote intestinal organoid growth. Additionally, Erdr1 accelerates scratch-wound closure in vitro, increases Lgr5+ intestinal stem cell regeneration following radiation-induced injury in vivo, and enhances recovery from dextran sodium sulfate (DSS)-induced colonic damage. Collectively, our findings indicate that early-life microbiota controls Erdr1-mediated intestinal epithelial proliferation and regeneration in response to mucosal damage.

    DOI: 10.1038/s41467-019-14258-z

    PubMed

    Other Link: http://www.nature.com/articles/s41467-019-14258-z

  15. Higher Levels of Streptococcus in Upper Gastrointestinal Mucosa Associated with Symptoms in Patients with Functional Dyspepsia. Reviewed International journal

    Akifumi Fukui, Tomohisa Takagi, Yuji Naito, Ryo Inoue, Saori Kashiwagi, Katsura Mizushima, Yutaka Inada, Ken Inoue, Akihito Harusato, Osamu Dohi, Tetsuya Okayama, Kazuhiro Katada, Kazuhiro Kamada, Kazuhiko Uchiyama, Takeshi Ishikawa, Osamu Handa, Yoshito Itoh, Masanori Nakagawa

    Digestion   Vol. 101 ( 1 ) page: 38 - 45   2020

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    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Functional dyspepsia (FD) is associated with poor health-related quality of life. Recent evidence suggests that the main pathogenesis suspect is the gut mucosa-associated microbiota (MAM). However, little is known about the MAM in FD subjects. The aim of this study was to clarify the relationship between upper gastrointestinal symptoms in FD and the characteristics of the gastrointestinal MAM. SUMMARY: Five mucosa samples from the upper gut (intraoral, mid-esophagus, gastric body, gastric antrum, and descending portion of the duodenum) were collected with a brush under endoscopic examination from FD and healthy control subjects. MAM profiles of each sample were analyzed by 16S-rRNA -V3-V4 gene sequences. Questionnaire was used to assess gastrointestinal symptoms in FD. Between FD and healthy control subjects, although the comparison of MAM α-diversity showed no significant differences, the structure of MAM (β-diversity) was clearly different. Only the phylum Firmicutes was increased in FD compared to healthy control subjects in all sites of the upper gut. At the genus level, Streptococcus was significantly increased in all sites in the upper gut in FD. The relative abundance of Streptococcus was positively correlated with upper gastrointestinal symptoms in each upper gut group. Furthermore, the relative abundance of OTU 90 was positively correlated with upper gastrointestinal symptoms in all sites in the upper gut in FD. Key Messages: Streptococcus is a bacterium strongly correlated with upper gastrointestinal symptoms in FD.

    DOI: 10.1159/000504090

    PubMed

  16. Pathological analysis of colorectal polyp specimens resected by advanced cold snare polypectomy technique. Reviewed

    春里暁人, 井村徹也, 中川知恵, 山内克真, 石破博, 福居顕文, 岡山哲也, 堅田和弘, 稲田裕, 伊藤義人

    京都府立医科大学附属北部医療センター誌   Vol. 6 ( 1 )   2020

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  17. Early-Life Microbiota Exposure Restricts Myeloid-Derived Suppressor Cell-Driven Colonic Tumorigenesis. Reviewed International journal

    Harusato A, Viennois E, Etienne-Mesmin L, Matsuyama S, Abo H, Osuka S, Lukacs NW, Naito Y, Itoh Y, Li JD, Merlin D, Gewirtz AT, Denning TL

    Cancer immunology research   Vol. 7 ( 4 ) page: 544 - 551   2019.4

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    Language:English   Publishing type:Research paper (scientific journal)  

    Gut microbiota and their metabolites are instrumental in regulating homeostasis at intestinal and extraintestinal sites. However, the complex effects of prenatal and early postnatal microbial exposure on adult health and disease outcomes remain incompletely understood. Here, we showed that mice raised under germ-free conditions until weaning and then transferred to specific pathogen-free (SPF) conditions harbored altered microbiota composition, augmented inflammatory cytokine and chemokine expression, and were hyper-susceptible to colitis-associated tumorigenesis later in adulthood. Increased number and size of colon tumors and intestinal epithelial cell proliferation in recolonized germ-free mice were associated with augmented intratumoral CXCL1, CXCL2, and CXCL5 expression and granulocytic myeloid-derived suppressor cell (G-MDSC) accumulation. Consistent with these findings, CXCR2 neutralization in recolonized germ-free mice completely reversed the exacerbated susceptibility to colitis-associated tumorigenesis. Collectively, our findings highlight a crucial role for early-life microbial exposure in establishing intestinal homeostasis that restrains colon cancer in adulthood.

    DOI: 10.1158/2326-6066.CIR-18-0444

    PubMed

  18. 肝硬変患者の肝性腹水・浮腫に対するTolvaptanの治療反応性の検討 Reviewed

    石破 博, 岡 浩平, 福居 顕文, 春里 暁人, 岡山 哲也, 堅田 和弘, 伊藤 義人

    京都府立医科大学附属北部医療センター誌   Vol. 5 ( 1 ) page: 17 - 23   2019.3

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    Language:Japanese   Publisher:京都府立医科大学附属北部医療センター  

    Tolvaptanは肝性腹水の治療に非常に有用な薬剤だが、日常臨床ではしばしば無効例を経験する。本研究ではTolvaptanへの反応性について、治療前後の腹水、肝予備能、血液生化学的検査の変化を検討したところ、Tolvaptanへの反応性は、腎機能、肝予備能に規定されることがわかった。またTolvaptan無効例でもアルブミン補充や腹水濾過再静注(CART)を併用することで、治療効果の改善を認めた。本研究は少数例の検討であり、今後症例の集積が必要である。(著者抄録)

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J06575&link_issn=&doc_id=20190701050003&doc_link_id=http%3A%2F%2Fid.nii.ac.jp%2F1327%2F00002233%2F&url=http%3A%2F%2Fid.nii.ac.jp%2F1327%2F00002233%2F&type=%8B%9E%93s%95%7B%97%A7%88%E3%89%C8%91%E5%8Aw%81F%8B%9E%93s%95%7B%97%A7%88%E3%89%C8%91%E5%8Aw%83%8A%83%7C%83W%83g%83%8A_%8Bk%88%E4&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80238_3.gif

  19. Combined IL-2 Immunocomplex and Anti-IL-5 mAb Treatment Expands Foxp3<sup>+</sup> Treg Cells in the Absence of Eosinophilia and Ameliorates Experimental Colitis. Reviewed International journal

    Abo H, Flannigan KL, Geem D, Ngo VL, Harusato A, Denning TL

    Frontiers in immunology   Vol. 10   page: 459 - 459   2019

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    Interleukin (IL)-2 is expressed during T cell activation and induces the proliferation and differentiation of T cells. CD4+Foxp3+ regulatory T cells (Tregs) constitutively express the high affinity IL-2 receptor (CD25/IL-2Rα) and rapidly respond to IL-2 to elaborate numerous suppressive mechanisms that limit immune-mediated pathologies. Accumulating evidence supports the concept that an aberrant balance between Tregs and Teff contribute to the pathology of intestinal inflammation and that the IL-2/Treg axis is a potential pathway to exploit for the treatment of inflammatory bowel disease (IBD). Here, we show that treatment of mice with IL-2/IL-2 antibody (JES6-1) immunocomplex during DSS-induced colitis induced Foxp3+ Treg expansion, but also potently stimulated GATA3+ type 2 innate lymphoid cell (ILC2) proliferation and high-level expression of IL-5. Furthermore, IL-2/JES6-1 treatment resulted in massive eosinophil accumulation and activation in the inflamed colon, and afforded only modest protection from colitis. In light of these findings, we observed that combined IL-2/JES6-1 and anti-IL-5 mAb treatment was most effective at ameliorating DSS-induced colitis compared to either treatment alone and that this regimen allowed for Foxp3+ Treg expansion without concomitant eosinophilia. Collectively, our findings provide insight into how blockade of IL-5 may aid in optimizing IL-2 immunotherapy for the treatment of intestinal inflammation.

    DOI: 10.3389/fimmu.2019.00459

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  20. Heme oxygenase-1 prevents murine intestinal inflammation. Reviewed

    Takagi T, Naito Y, Mizushima K, Hirai Y, Harusato A, Okayama T, Katada K, Kamada K, Uchiyama K, Handa O, Ishikawa T, Itoh Y

    Journal of clinical biochemistry and nutrition   Vol. 63 ( 3 ) page: 169 - 174   2018.11

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  21. A cytokine network involving IL-36γ, IL-23, and IL-22 promotes antimicrobial defense and recovery from intestinal barrier damage. Reviewed International journal

    Ngo VL, Abo H, Maxim E, Harusato A, Geem D, Medina-Contreras O, Merlin D, Gewirtz AT, Nusrat A, Denning TL

    Proceedings of the National Academy of Sciences of the United States of America   Vol. 115 ( 22 ) page: E5076 - E5085   2018.5

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    The gut epithelium acts to separate host immune cells from unrestricted interactions with the microbiota and other environmental stimuli. In response to epithelial damage or dysfunction, immune cells are activated to produce interleukin (IL)-22, which is involved in repair and protection of barrier surfaces. However, the specific pathways leading to IL-22 and associated antimicrobial peptide (AMP) production in response to intestinal tissue damage remain incompletely understood. Here, we define a critical IL-36/IL-23/IL-22 cytokine network that is instrumental for AMP production and host defense. Using a murine model of intestinal damage and repair, we show that IL-36γ is a potent inducer of IL-23 both in vitro and in vivo. IL-36γ-induced IL-23 required Notch2-dependent (CD11b+CD103+) dendritic cells (DCs), but not Batf3-dependent (CD11b-CD103+) DCs or CSF1R-dependent macrophages. The intracellular signaling cascade linking IL-36 receptor (IL-36R) to IL-23 production by DCs involved MyD88 and the NF-κB subunits c-Rel and p50. Consistent with in vitro observations, IL-36R- and IL-36γ-deficient mice exhibited dramatically reduced IL-23, IL-22, and AMP levels, and consequently failed to recover from acute intestinal damage. Interestingly, impaired recovery of mice deficient in IL-36R or IL-36γ could be rescued by treatment with exogenous IL-23. This recovery was accompanied by a restoration of IL-22 and AMP expression in the colon. Collectively, these data define a cytokine network involving IL-36γ, IL-23, and IL-22 that is activated in response to intestinal barrier damage and involved in providing critical host defense.

    DOI: 10.1073/pnas.1718902115

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  22. Insights on the impact of diet-mediated microbiota alterations on immunity and diseases. Reviewed

    Harusato A, Chassaing B

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons   Vol. 18 ( 3 ) page: 550 - 555   2018.3

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  23. IL-36 gamma signaling controls the induced regulatory T cell-Th9 cell balance via NFkB activation and STAT transcription factors Reviewed

    A. Harusato, H. Abo, V. L. Ngo, S. W. Yi, K. Mitsutake, S. Osuka, J. E. Kohlmeier, J. D. Li, A. T. Gewirtz, A. Nusrat, T. L. Denning

    MUCOSAL IMMUNOLOGY   Vol. 10 ( 6 ) page: 1455 - 1467   2017.11

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    Regulatory and effector T helper (Th) cells are abundant at mucosal surfaces, especially in the intestine, where they control the critical balance between tolerance and inflammation. However, the key factors that reciprocally dictate differentiation along these specific lineages remain incompletely understood. Here we report that the interleukin-1 (IL-1) family member IL-36 gamma signals through IL-36 receptor, myeloid differentiation primary response gene 88, and nuclear factor-kappa Bp50 in CD4(+) T cells to potently inhibit Foxp3-expressing induced regulatory T cell (T-reg) development, while concomitantly promoting the differentiation of Th9 cells via a IL-2-STAT5- (signal transducer and activator of transcription factor 5) and IL-4-STAT6-dependent pathway. Consistent with these findings, mice deficient in IL-36 gamma were protected from Th cell-driven intestinal inflammation and exhibited increased colonic T-reg cells and diminished Th9 cells. Our findings thus reveal a fundamental contribution for the IL-36/IL-36R axis in regulating the T-reg-Th9 cell balance with broad implications for Th cell-mediated disorders, such as inflammatory bowel diseases and particularly ulcerative colitis.

    DOI: 10.1038/mi.2017.21

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  24. IL-17A-mediated neutrophil recruitment limits expansion of segmented filamentous bacteria Reviewed

    K. L. Flannigan, V. L. Ngo, D. Geem, A. Harusato, S. A. Hirota, C. A. Parkos, N. W. Lukacs, A. Nusrat, V. Gaboriau-Routhiau, N. Cerf-Bensussan, A. T. Gewirtz, T. L. Denning

    MUCOSAL IMMUNOLOGY   Vol. 10 ( 3 ) page: 673 - 684   2017.5

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    Specific components of the intestinal microbiota are capable of influencing immune responses such that a mutualistic relationship is established. In mice, colonization with segmented filamentous bacteria (SFB) induces T-helper-17 (Th17) cell differentiation in the intestine, yet the effector functions of interleukin (IL)-17A in response to SFB remain incompletely understood. Here we report that colonization of mice with SFB-containing microbiota induced IL-17A-and CXCR2-dependent recruitment of neutrophils to the ileum. This response required adaptive immunity, as Rag-deficient mice colonized with SFB-containing microbiota failed to induce IL-17A, CXCL1 and CXCL2, and displayed defective neutrophil recruitment to the ileum. Interestingly, neutrophil depletion in wild-type mice resulted in significantly augmented Th17 responses and SFB expansion, which correlated with impaired expression of IL-22 and antimicrobial peptides. These data provide novel insight into a dynamic IL-17A-CXCR2-neutrophil axis during acute SFB colonization and demonstrate a central role for neutrophils in limiting SFB expansion.

    DOI: 10.1038/mi.2016.80

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  25. Contribution of Mesenteric Lymph Nodes and GALT to the Intestinal Foxp3+ Regulatory T-Cell Compartment. Reviewed

    Geem D, Ngo V, Harusato A, Chassaing B, Gewirtz AT, Newberry RD, Denning TL

    Cellular and molecular gastroenterology and hepatology   Vol. 2 ( 3 ) page: 274 - 280   2016.5

  26. Cutting Edge: IL-36 Receptor Promotes Resolution of Intestinal Damage Reviewed

    Oscar Medina-Contreras, Akihito Harusato, Hikaru Nishio, Kyle L. Flannigan, Vu Ngo, Giovanna Leoni, Philipp-Alexander Neumann, Duke Geem, Loukia N. Lili, Ravisankar A. Ramadas, Benoit Chassaing, Andrew T. Gewirtz, Jacob E. Kohlmeier, Charles A. Parkos, Jennifer E. Towne, Asma Nusrat, Timothy L. Denning

    JOURNAL OF IMMUNOLOGY   Vol. 196 ( 1 ) page: 34 - 38   2016.1

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    IL-1 family members are central mediators of host defense. In this article, we show that the novel IL-1 family member IL-36 gamma was expressed during experimental colitis and human inflammatory bowel disease. Germ-free mice failed to induce IL-36 gamma in response to dextran sodium sulfate (DSS)-induced damage, suggesting that gut microbiota are involved in its induction. Surprisingly, IL-36R-deficient (Il1rl2(-/-)) mice exhibited defective recovery following DSS-induced damage and impaired closure of colonic mucosal biopsy wounds, which coincided with impaired neutrophil accumulation in the wound bed. Failure of Il1rl2(-/-) mice to recover from DSS-induced damage was associated with a profound reduction in IL-22 expression, particularly by colonic neutrophils. Defective recovery of Il1rl2(-/-) mice could be rescued by an aryl hydrocarbon receptor agonist, which was sufficient to restore IL-22 expression and promote full recovery from DSS-induced damage. These findings implicate the IL-36/IL-36R axis in the resolution of intestinal mucosal wounds.

    DOI: 10.4049/jimmunol.1501312

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  27. Macrophage Isolation from the Mouse Small and Large Intestine. Reviewed

    Harusato A, Geem D, Denning TL

    Methods in molecular biology (Clifton, N.J.)   Vol. 1422   page: 171 - 180   2016

  28. Intestinal, Antigen-Presenting Cells Key Regulators of Immune Homeostasis and Inflammation Reviewed

    Kyle L. Flannigan, Duke Geem, Akihito Harusato, Timothy L. Denning

    AMERICAN JOURNAL OF PATHOLOGY   Vol. 185 ( 7 ) page: 1809 - 1819   2015.7

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    The microbiota that populate the mammalian intestine are critical for proper host physiology, yet simultaneously pose a potential danger. Intestinal antigen-presenting cells, namely macrophages and dendritic cells (DCs), are integral components of the mucosal innate immune system that maintain coexistence with the microbiota in face of this constant threat. Intestinal macrophages and DCs integrate signals from the microenvironment to orchestrate innate and adaptive immune responses that ultimately Lead to durable tolerance of the microbiota. Tolerance is not a default response, however, because macrophages and DCs remain poised to vigorously respond to pathogens that breach the epithelial barrier. In this review, we summarize the salient features of macrophages and DCs in the healthy and inflamed intestine and discuss how signals from the microbiota can influence their function.

    DOI: 10.1016/j.ajpath.2015.02.024

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  29. Harnessing Regulatory T Cells for the Treatment of Inflammatory Bowel Disease Reviewed

    Duke Geem, Akihito Harusato, Kyle Flannigan, Timothy L. Denning

    INFLAMMATORY BOWEL DISEASES   Vol. 21 ( 6 ) page: 1409 - 1418   2015.6

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    Regulatory CD4(+) T (T-reg) cells are comprised of a heterogeneous population of cells that play a vital role in suppressing inflammation and maintaining immune tolerance. The immunoregulatory function of T-reg cells is especially important in the intestine where the mucosa is exposed to a diverse array of foreign antigensincluding those derived from food and commensal bacteria. T-reg cells are enriched in the intestinal lamina propria and provide a crucial function in promoting tolerance to enteric antigens while modulating tissue inflammation. Correspondingly, T-reg cell dysfunction is associated with a breakdown in intestinal tolerance and the induction of aberrant immune responses that may contribute to the pathogenesis of inflammatory bowel disease. This review will provide a brief overview of T-reg cell biology with a focus on Foxp3(+) T-reg and type 1 regulatory (Tr1) cells and summarize the evidence for defective T-reg cells in experimental and human inflammatory bowel disease. The potential application of T-reg cells as a treatment for inflammatory bowel disease will also be discussed in the context of T-reg infusion therapy and the in vivo induction/expansion of intestinal T-reg cells.

    DOI: 10.1097/MIB.0000000000000343

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  30. Phenotypic and functional profiling of mouse intestinal antigen presenting cells Reviewed

    Akihito Harusato, Kyle L. Flannigan, Duke Geem, Timothy L. Denning

    JOURNAL OF IMMUNOLOGICAL METHODS   Vol. 421   page: 20 - 26   2015.6

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    The microbiota that populates the mammalian intestine consists of hundreds of trillions of bacteria that are separated from underlying immune cells by a single layer of epithelial cells. The intestinal immune system effectively tolerates components of the microbiota that provide benefit to the host while remaining poised to eliminate those that are harmful. Antigen presenting cells, especially macrophages and dendritic cells, play important roles in maintaining intestinal homeostasis via their ability to orchestrate appropriate responses to the microbiota. Paramount to elucidating intestinal macrophage- and dendritic cell-mediated functions is the ability to effectively isolate and identify these cells from a complex cellular environment. In this review, we summarize methodology for the isolation and phenotypic characterization of macrophages and DCs from the mouse intestine and discuss how this may be useful for gaining insight into the mechanisms by which mucosal immune tolerance is maintained. (C) 2015 Elsevier B.V. All rights reserved.

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  31. Preventive effect of agaro-oligosaccharides on non-steroidal anti-inflammatory drug-induced small intestinal injury in mice Reviewed

    Yasuki Higashimura, Yuji Naito, Tomohisa Takagi, Yuko Tanimura, Katsura Mizushima, Akihito Harusato, Akifumi Fukui, Hiroyuki Yoriki, Osamu Handa, Hiromu Ohnogi, Toshikazu Yoshikawa

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   Vol. 29 ( 2 ) page: 310 - 317   2014.2

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    Background and Aim: Non-steroidal anti-inflammatory drugs (NSAIDs), which are commonly used in clinical medicine, cause erosion, ulcers, and bleeding in the gastrointestinal tract. No effective agent for the prevention and treatment of small intestinal injury by NSAIDs has been established. This study investigates the effects of agaro-oligosaccharides (AGOs) on NSAID-induced small intestinal injury in mice.
    Methods: Mice were treated with indomethacin, an NSAID, to induce intestinal injury. The respective degrees of mucosal injury of mice that received AGO and control mice were compared. Heme oxygenase-1 (HO-1) expression using quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry were measured. The expression of keratinocyte chemoattractant (KC) was measured using qRT-PCR and enzyme-linked immunosorbent assay.
    Results: AGO administration induced HO-1 expression in mouse small intestinal mucosa. Induction was observed mainly in F4/80 positive macrophages. The increased ulcers score, myeloperoxidase activity, and KC expression by indomethacin were inhibited by AGO administration. Conversely, HO inhibitor cancelled AGO-mediated prevention of intestinal injury. In mouse peritoneal macrophages, AGOs enhanced HO-1 expression and suppressed lipopolysaccharide-induced KC expression. Furthermore, AGOs enhanced the expressions of alternatively activated macrophage markers arginase-1, mannose receptor-1, and chitinase 3-like 3.
    Conclusions: Results suggest that oral administration of AGOs prevents NSAID-induced intestinal injury.

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  32. Oligosaccharides from agar inhibit murine intestinal inflammation through the induction of heme oxygenase-1 expression. Reviewed

    Yasuki Higashimura, Yuji Naito, Tomohisa Takagi, Katsura Mizushima, Yasuko Hirai, Akihito Harusato, Hiromu Ohnogi, Ryoichi Yamaji, Hiroshi Inui, Yoshihisa Nakano, Toshikazu Yoshikawa

    Journal of gastroenterology   Vol. 48 ( 8 ) page: 897 - 909   2013.8

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    BACKGROUND: Agarose is hydrolyzed easily to yield oligosaccharides, designated as agaro-oligosaccharides (AGOs). Recently, it has been demonstrated that AGOs induce heme oxygenase-1 (HO-1) expression in macrophages and that they might lead to anti-inflammatory property. Nevertheless, the molecular mechanism of AGO-mediated HO-1 induction remains unknown, as does AGOs' ability to elicit anti-inflammatory activity in vivo. This study was undertaken to uncover the mechanism of AGO-mediated HO-1 induction and to investigate the therapeutic effect of AGOs on intestinal inflammation. METHODS: Mice were treated with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to induce colitis. The respective degrees of mucosal injury of mice that had received AGO and control mice were compared. We investigated HO-1 expression using Western blotting, quantitative real-time PCR (qRT-PCR), and immunohistochemistry. The expression of tumor necrosis factor-α (TNF-α) was measured using qRT-PCR and enzyme-linked immunosorbent assay. RESULTS: AGO administration induced HO-1 expression in colonic mucosa. The induction was observed mainly in F4/80 positive macrophages. Increased colonic damage and myeloperoxidase activity after TNBS treatment were inhibited by AGO administration. TNBS treatment induced TNF-α expression, and AGO administration suppressed induction. However, HO inhibitor canceled AGO-mediated amelioration of colitis. In RAW264 cells, AGOs enhanced HO-1 expression time-dependently and concentration-dependently and suppressed lipopolysaccharide-induced TNF-α expression. Furthermore, agarotetraose-mediated HO-1 induction required NF-E2-related factor 2 function and phosphorylation of c-jun N-terminal kinase. CONCLUSIONS: We infer that AGO administration inhibits TNBS-induced colitis in mice through HO-1 induction in macrophages. Consequently, oral administration of AGOs might be an important therapeutic strategy for inflammatory bowel disease.

    DOI: 10.1007/s00535-012-0719-4

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  33. Hemin ameliorates indomethacin-induced small intestinal injury in mice through the induction of heme oxygenase-1. Reviewed International journal

    Hiroyuki Yoriki, Yuji Naito, Tomohisa Takagi, Katsura Mizusima, Yasuko Hirai, Akihito Harusato, Shinya Yamada, Toshifumi Tsuji, Munehiro Kugai, Akifumi Fukui, Yasuki Higashimura, Kazuhiko Katada, Kazuhiro Kamada, Kazuhiko Uchiyama, Osamu Handa, Nobuaki Yagi, Hiroshi Ichikawa, Toshikazu Yosikawa

    Journal of gastroenterology and hepatology   Vol. 28 ( 4 ) page: 632 - 8   2013.4

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    BACKGROUND AND AIM: Although non-steroidal anti-inflammatory drugs can induce intestinal injury, the mechanisms are not fully understood, and treatment has yet to be established. Heme oxygenase-1 (HO-1) has recently gained attention for anti-inflammatory and cytoprotective effects. This study aimed to investigate the effects of hemin, an HO-1 inducer, on indomethacin-induced enteritis in mice. METHODS: Enteritis was induced by single subcutaneous administration of indomethacin (10 mg/kg) in male C57BL/6 mice. Hemin (30 mg/kg) was administered by intraperitoneal administration 6 h before indomethacin administration. Mice were randomly divided into four groups: (i) sham + vehicle; (ii) sham + hemin; (iii) indomethacin + vehicle; or (iv) indomethacin + hemin. Enteritis was evaluated by measuring ulcerative lesions. Myeloperoxidase activity was measured as an index of neutrophil accumulation. The mRNA expression of inflammatory cytokines and chemokines, such as tumor necrosis factor-α, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and keratinocyte chemoattractant, were analyzed by real-time polymerase chain reaction. RESULTS: The area of ulcerative lesions, myeloperoxidase activity, and mRNA expression of inflammatory cytokines and chemokines were significantly increased in mice administrated with indomethacin compared with vehicle-treated sham mice. Development of intestinal lesions, increased levels of myeloperoxidase activities, and mRNA expressions of inflammatory cytokines and chemokines were significantly suppressed in mice treated with hemin compared with vehicle-treated mice. Protective effects of hemin were reversed by co-administration of tin protoporphyrin, an HO-1 inhibitor. CONCLUSIONS: Induction of HO-1 by hemin inhibits indomethacin-induced intestinal injury through upregulation of HO-1. Pharmacological induction of HO-1 may offer a novel therapeutic strategy to prevent indomethacin-induced small intestinal injury.

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  34. BTB and CNC Homolog 1 (Bach1) Deficiency Ameliorates TNBS Colitis in Mice: Role of M2 Macrophages and Heme Oxygenase-1 Reviewed

    Akihito Harusato, Yuji Naito, Tomohisa Takagi, Kazuhiko Uchiyama, Katsura Mizushima, Yasuko Hirai, Yasuki Higashimura, Kazuhiro Katada, Osamu Handa, Takeshi Ishikawa, Nobuaki Yagi, Satoshi Kokura, Hiroshi Ichikawa, Akihiko Muto, Kazuhiko Igarashi, Toshikazu Yoshikawa

    INFLAMMATORY BOWEL DISEASES   Vol. 19 ( 4 ) page: 740 - 753   2013.3

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    Background: BTB and CNC homolog 1 (Bach1) is a transcriptional repressor of heme oxygenase-1 (HO-1), which plays an important role in the protection of cells and tissues against acute and chronic inflammation. However, the role of Bach1 in the gastrointestinal mucosal defense system remains little understood. HO-1 supports the suppression of experimental colitis and localizes mainly in macrophages in colonic mucosa. This study was undertaken to elucidate the Bach1/HO-1 system's effects on the pathogenesis of experimental colitis.
    Methods: This study used C57BL/6 (wild-type) and homozygous Bach1-deficient C57BL/6 mice in which colonic damage was induced by the administration of an enema of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Subsequently, they were evaluated macroscopically, histologically, and biochemically. Peritoneal macrophages from the respective mice were isolated and analyzed. Then, wild-type mice were injected with peritoneal macrophages from the respective mice. Acute colitis was induced similarly.
    Results: TNBS-induced colitis was inhibited in Bach1-deficient mice. TNBS administration increased the expression of HO-1 messenger RNA and protein in colonic mucosa in Bach1-deficient mice. The expression of HO-1 mainly localized in F4/80-immunopositive and CD11b-immunopositive macrophages. Isolated peritoneal macrophages from Bach1-deficient mice highly expressed HO-1 and also manifested M2 macrophage markers, such as Arginase-1, Fizz-1, Ym1, and MRC1. Furthermore, TNBS-induced colitis was inhibited by the transfer of Bach1-deficient macrophages into wild-type mice.
    Conclusions: Deficiency of Bach1 ameliorated TNBS-induced colitis. Bach1-deficient macrophages played a key role in protection against colitis. Targeting of this mechanism is applicable to cell therapy for human inflammatory bowel disease. (Inflamm Bowel Dis 2013;19:740-753)

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  35. Rebamipide ameliorates indomethacin-induced small intestinal injury in rats via the inhibition of matrix metalloproteinases activity. Reviewed International journal

    Shinya Yamada, Yuji Naito, Tomohisa Takagi, Katsura Mizushima, Ryusuke Horie, Kohei Fukumoto, Ken Inoue, Akihito Harusato, Kazuhiko Uchiyama, Osamu Handa, Nobuaki Yagi, Hiroshi Ichikawa, Toshikazu Yoshikawa

    Journal of gastroenterology and hepatology   Vol. 27 ( 12 ) page: 1816 - 24   2012.12

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    BACKGROUND AND AIM: The pathogenesis of non-steroidal anti-inflammatory drugs (NSAIDs)-induced small intestinal lesions remains unclear, although it is considered to be quite different from that of upper gastrointestinal tract ulcers due to the absence of acid and the presence of bacteria and bile in the small intestine. The aim of this study was to characterize specific gene expression profiles of intestinal mucosa in indomethacin-induced small intestinal injury, and to investigate the effects of rebamipide on the expression of these genes. METHODS: Intestinal injury was induced in male Wistar rats by subcutaneous administration of indomethacin. Total RNA of the intestinal mucosa was extracted 24 h after indomethacin administration, gene expression was investigated using microarray analysis, and the identified genes were confirmed by real-time polymerase chain reaction (PCR). In addition, we investigated whether the treatment with rebamipide altered the expression of these identified genes. RESULTS: The administration of indomethacin induced small intestine injuries, and these lesions were significantly inhibited by the treatment with rebamipide. Microarray analysis showed that the genes for several matrix metalloproteinases (MMPs) and several chemokine-related genes were significantly upregulated, and metallothionein 1a (MT1a) was downregulated in the intestinal mucosa after administration of indomethacin. The expressions of these genes were reversed by the treatment with rebamipide. CONCLUSION: These data suggest that MMPs, chemokines, and MT1a may play an important role in the intestinal mucosal injury induced by indomethacin. In particular, the inhibition of MMP genes and chemokine-related genes by rebamipide may be important for the therapeutic effect against NSAIDs-induced small intestinal injury.

    DOI: 10.1111/j.1440-1746.2012.07275.x

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  36. Serpin B1 protects colonic epithelial cell via blockage of neutrophil elastase activity and its expression is enhanced in patients with ulcerative colitis. Reviewed International journal

    Kazuhiko Uchiyama, Yuji Naito, Tomohisa Takagi, Katsura Mizushima, Yasuko Hirai, Natsuko Hayashi, Akihito Harusato, Ken Inoue, Kohei Fukumoto, Shinya Yamada, Osamu Handa, Takeshi Ishikawa, Nobuaki Yagi, Satoshi Kokura, Toshikazu Yoshikawa

    American journal of physiology. Gastrointestinal and liver physiology   Vol. 302 ( 10 ) page: G1163-70 - 70   2012.5

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    Serpin B1 is a monocyte neutrophil elastase (NE) inhibitor and is one of the most efficient inhibitors of NE. In the present study, we investigated the role of serpin B1 in the pathogenesis of ulcerative colitis by using clinical samples and an experimental model. The colonic expression of serpin B1 was determined by real-time polymerase chain reaction (PCR), Western blot analysis, and immunohistological studies in both normal and inflamed mucosa from patients with ulcerative colitis. Serpin B1 mRNA expression was determined by real-time PCR in the mouse dextran sodium sulfate (DSS)-induced colitis model. Young adult mouse colonic epithelial (YAMC) cells were used to determine the role of serpin B1. Serpin B1 gene transfected YAMC cells were treated with H(2)O(2) to measure cell viability. The expression of NE was determined in YAMC cells treated with H(2)O(2). NE-silenced YAMC cells were also treated with H(2)O(2) and then measured for viability. Upregulated expression of serpin B1 in colonic mucosa was confirmed from patients with active ulcerative colitis. Immunohistochemical studies showed that serpin B1 expression was localized not only in inflammatory infiltration cells but also in epithelial cells. Serpin B1 mRNA expression was also increased in colonic mucosa of mouse DSS-induced colitis. Serpin B1-transfected YAMC cells were resistant against the treatment of H(2)O(2). H(2)O(2) treatment significantly induced NE in YAMC cells, and NE-silenced YAMC cells were also resistant against the treatment of H(2)O(2). These results suggest that serpin B1 may be a novel marker of active ulcerative colitis and may play an important role in the pathogenesis of inflammatory bowel disease.

    DOI: 10.1152/ajpgi.00292.2011

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  37. Suppression of indomethacin-induced apoptosis in the small intestine due to Bach1 deficiency. Reviewed International journal

    Akihito Harusato, Yuji Naito, Tomohisa Takagi, Kazuhiko Uchiyama, Katsura Mizushima, Yasuko Hirai, Shinya Yamada, Toshifumi Tuji, Hiroyuki Yoriki, Ryusuke Horie, Ken Inoue, Kohei Fukumoto, Osamu Handa, Takeshi Ishikawa, Satoshi Kokura, Yukiko Minamiyama, Hiroshi Ichikawa, Akihiko Muto, Kazuhiko Igarashi, Toshikazu Yoshikawa

    Free radical research   Vol. 45 ( 6 ) page: 717 - 27   2011.6

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    BTB and CNC homologue 1 (Bach1) is a transcriptional repressor of heme oxygenase-1 (HO-1). This study hypothesized that Bach1 plays an important role in the indomethacin-induced apoptosis in the case of small-intestinal mucosal injury. Eight-week-old male C57BL/6 (wild-type) and homozygous Bach1-deficient C57BL/6 mice were included in this study. Mucosal injuries induced by subcutaneously administering indomethacin were evaluated macroscopically, histologically and biochemically. Indomethacin-induced injuries were improved in Bach1-deficient mice. Immunohistochemistry showed an increase in the number of HO-1-positive cells, which were mainly F4/80 positive macrophages, in Bach1-deficient mice. Indomethacin administration increased the expression of HO-1 mRNA and protein in the small intestine in Bach1-deficient mice. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining showed that the extent of apoptosis was suppressed in Bach1-deficent mice. In conclusion, deficiency of the Bach1 gene inhibited apoptosis and thus suppressed mucosal injury, indicating that Bach1 is a novel therapeutic target for indomethacin-induced intestinal injury.

    DOI: 10.3109/10715762.2011.574287

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  38. Role of tumor necrosis factor-α in the pathogenesis of indomethacin-induced small intestinal injury in mice. Reviewed International journal

    Kohei Fukumoto, Yuji Naito, Tomohisa Takagi, Shinya Yamada, Ryusuke Horie, Ken Inoue, Akihito Harusato, Ikuhiro Hirata, Tastushi Omatsu, Katsura Mizushima, Yasuko Hirai, Naohisa Yoshida, Kazuhiko Uchiyama, Takeshi Ishikawa, Osamu Handa, Hideyuki Konishi, Naoki Wakabayashi, Nobuaki Yagi, Satoshi Kokura, Hiroshi Ichikawa, Masakazu Kita, Toshikazu Yoshikawa

    International journal of molecular medicine   Vol. 27 ( 3 ) page: 353 - 9   2011.3

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    The pathogenesis of small intestinal damage caused by non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin is still unclear. For this reason, there is currently no therapeutic strategy for ameliorating such damage. On the other hand, molecular treatment strategies targeting tumor necrosis factor (TNF)-α exert beneficial effects on intestinal lesions in patients with inflammatory bowel disease (IBD). To clarify the participation of TNF-α in NSAID-induced small intestinal damage, we investigated the effects of indomethacin administration in mice with targeted deletion of the TNF-α gene. Indomethacin (10 mg/kg) was administered subcutaneously to male C57BL/6 (wild-type: WT) mice and TNF-α-deficient (TNF-α-/-) mice to induce small intestinal damage. The ulcer score, the tissue-associated myeloperoxidase (MPO) activity as an index of neutrophil infiltration, and the expression of keratinocyte chemoattractant (KC) mRNA in the small intestinal mucosa were measured. In addition, we performed a TUNEL assay to evaluate indomethacin-induced apoptosis of intestinal epithelial cells and measured the expression of caspase-3 protein and Bcl-2 mRNA. The ulcer score, MPO activity, and expression of KC mRNA were significantly increased after indomethacin administration. These increases were significantly inhibited in TNF-α-/- mice compared with WT mice. Apoptotic cells were observed by the TUNEL assay in the area of the ulcerative lesion, and they were significantly fewer in TNF-α-/- mice compared with WT mice. The expression of cleaved caspase-3 protein was induced by indomethacin administration, and significantly inhibited in TNF-α-/- mice compared with that of WT mice. The expression level of Bcl-2 mRNA in indomethacin-treated TNF-α-/- mice was significantly higher than that in WT mice. TNF-α plays an important role in the pathogenesis of indomethacin-induced small intestinal damage. These results suggest that TNF-α could become a new therapeutic target for NSAID-induced small intestinal damage.

    DOI: 10.3892/ijmm.2011.602

    PubMed

  39. Reduced small-intestinal injury induced by indomethacin in interleukin-17A-deficient mice Reviewed

    Shinya Yamada, Yuji Naito, Tomohisa Takagi, Katsura Mizushima, Yasuko Hirai, Ryusuke Horie, Kohei Fukumoto, Ken Inoue, Akihito Harusato, Naohisa Yoshida, Kazuhiko Uchiyama, Osamu Handa, Takeshi Ishikawa, Hideyuki Konishi, Naoki Wakabayashi, Nobuaki Yagi, Satoshi Kokura, Masakazu Kita, Toshikazu Yoshikawa

    Journal of Gastroenterology and Hepatology (Australia)   Vol. 26 ( 2 ) page: 398 - 404   2011

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    Background and Aims: The pathogenesis of enteropathy induced by non-steroidal anti-inflammatory drugs (NSAIDs) is still unclear, and there are no established treatments. Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has been associated with the development of chronic inflammatory diseases, including autoimmune diseases. To define the role of IL-17A in small intestinal injury and inflammation, we studied the effects of indomethacin administration in mice with targeted deletions of the IL-17A gene. Methods: Male C57BL/6 (wild-type) and homozygous IL-17A-/- C57BL/6 mice were subjected to this study. Indomethacin (10mg/kg) was subcutaneously administered to induce small-intestinal damage. Indomethacin-induced lesions in the small intestine were evaluated by measuring the injured area and by histopathology. Also assessed were myeloperoxidase (MPO) activity, as an index of neutrophil accumulation, and intestinal mRNA expression for inflammatory cytokines. Results: The area of macroscopic ulcerative lesions, the MPO activity and the mRNA expression of inflammatory-associated chemokines, such as keratinocyte chemoattractant (KC), monocyte chemotactic protein-1 (MCP-1), and granulocyte-colony stimulating factor (G-CSF), were significantly increased in indomethacin-treated groups compared with the sham groups. The development of intestinal lesions by indomethacin was inhibited in IL-17A-/- mice compared with wild-type mice, together with significant suppression of the increased levels of MPO activities and KC, MCP-1, and G-CSF levels. Conclusion: These findings demonstrate that IL-17A contributes to the development of indomethacin-induced small intestinal injury through upregulation of G-CSF, KC, and MCP-1. IL-17A might be a promising new therapeutic target to treat NSAID-induced enteritis. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

    DOI: 10.1111/j.1440-1746.2010.06496.x

    Scopus

    PubMed

  40. Daikenchuto, a Kampo medicine, regulates intestinal fibrosis associated with decreasing expression of heat shock protein 47 and collagen content in a rat colitis model. Reviewed

    Ken Inoue, Yuji Naito, Tomohisa Takagi, Natsuko Hayashi, Yasuko Hirai, Katsura Mizushima, Ryusuke Horie, Kohei Fukumoto, Shinya Yamada, Akihito Harusato, Ikuhiro Hirata, Tatsushi Omatsu, Naohisa Yoshida, Kazuhiko Uchiyama, Takeshi Ishikawa, Osamu Handa, Hideyuki Konishi, Naoki Wakabayashi, Nobuaki Yagi, Hiroshi Ichikawa, Satoshi Kokura, Toshikazu Yoshikawa

    Biological & pharmaceutical bulletin   Vol. 34 ( 11 ) page: 1659 - 65   2011

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    Heat shock protein (HSP) 47 may play an important role in the pathogenesis of intestinal fibrosis. Daikenchuto (DKT), a traditional Japanese herbal (Kampo) medicine, has been reported to ameliorate intestinal inflammation. The aims of this study were to determine time-course profiles of several parameters of fibrosis in a rat model, to confirm the HSP47-expressing cells in the colon, and finally to evaluate DKT's effects on intestinal fibrosis. Colitis was induced in male Wistar rats weighing 200 g using an enema of trinitrobenzene sulfonic acid (TNBS). HSP47 localization was determined by immunohistochemistry. Colonic inflammation and fibrosis were assessed by macroscopic, histological, morphometric, and immunohistochemical analyses. Colonic mRNA expression of transforming growth factor β1 (TGF-β1), HSP47, and collagen type I were assessed by real time-polymerase chain reaction (PCR). DKT was administered orally once a day from 8 to 14 d after TNBS administration. The colon was removed on the 15th day. HSP47 immunoreactivity was coexpressed with α-smooth muscle actin-positive cells located in the subepithelial space. Intracolonic administration of TNBS resulted in grossly visible ulcers. Colonic inflammation persisted for 6 weeks, and fibrosis persisted for 4 weeks after cessation of TNBS treatment. The expression levels of mRNA and proteins for TGF-β1, HSP47, and collagen I were elevated in colonic mucosa treated with TNBS. These fibrosis markers indicated that DKT treatment significantly inhibited TNBS-induced fibrosis. These findings suggest that DKT reduces intestinal fibrosis associated with decreasing expression of HSP47 and collagen content in the intestine.

    PubMed

  41. Reactive oxygen species-quenching and anti-apoptotic effect of polaprezinc on indomethacin-induced small intestinal epithelial cell injury. Reviewed

    Tatsushi Omatsu, Yuji Naito, Osamu Handa, Katsura Mizushima, Natsuko Hayashi, Ying Qin, Akihito Harusato, Ikuhiro Hirata, Etsuko Kishimoto, Hitomi Okada, Kazuhiko Uchiyama, Takeshi Ishikawa, Tomohisa Takagi, Nobuaki Yagi, Satoshi Kokura, Hiroshi Ichikawa, Toshikazu Yoshikawa

    Journal of gastroenterology   Vol. 45 ( 7 ) page: 692 - 702   2010.7

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    BACKGROUND: To protect the small intestine from mucosal injury induced by nonsteroidal anti-inflammatory drugs is one of the critical issues in the field of gastroenterology. Polaprezinc (PZ), a gastric muco-protecting agent, has been widely used for the treatment of gastric ulcer and gastritis for its unique effects, such as its strong reactive oxygen species (ROS)-quenching effect. The aim of this study was to clarify the mechanism by which indomethacin-induced small intestinal mucosal injury occurs, by using a rat intestinal epithelial cell line (RIE-1). In addition, the protective role of PZ and the possible mechanism of its effect on indomethacin-induced small intestinal injury were investigated. METHODS: Cell death was evaluated by methyl thiazolyl tetrazolium (MTT) assay and a double-staining method with Hoechst33342 dye and propidium iodide. Indomethacin-induced ROS production was evaluated by detecting the oxidation of a redox-sensitive fluorogenic probe, RedoxSensor, and the oxidation of cysteine residues of proteins (protein S oxidation). The activation of cytochrome c, smac/DIABLO, and caspase-3 was assessed by western blotting. In some experiments, PZ or its components, L: -carnosine and zinc, were used. RESULTS: We found that indomethacin caused apoptosis in RIE-1 cells in a dose- and time-dependent manner. Indomethacin also induced ROS production and an increase in the protein S oxidation of RIE-1. Pretreatment of RIE-1 with PZ or zinc sulfate, but not L: -carnosine, significantly reduced the indomethacin-induced apoptosis. PZ prevented ROS production and the increase in protein S-oxidation. PZ inhibited indomethacin-induced cytochrome c and smac/DIABLO release and subsequent caspase-3 activation. CONCLUSIONS: The protective effect of PZ on indomethacin-induced small intestinal injury may be dependent on its ROS-quenching effect.

    DOI: 10.1007/s00535-010-0213-9

    Web of Science

    PubMed

  42. Carbon monoxide enhance colonic epithelial restitution via FGF15 derived from colonic myofibroblasts Reviewed

    Kazuhiko Uchiyama, Yuji Naito, Tomohisa Takagi, Katsura Mizushima, Natsuko Hayashi, Akihito Harusato, Ikuhiro Hirata, Tatsushi Omatsu, Osamu Handa, Takeshi Ishikawa, Nobuaki Yagi, Satoshi Kokura, Toshikazu Yoshikawa

    Biochemical and Biophysical Research Communications   Vol. 391 ( 1 ) page: 1122 - 1126   2010.1

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    Carbon monoxide (CO) has been reported to ameliorate colonic inflammation and improve experimental colitis. It is well known that mucosal restitution is important to improve colitis as well as reduction of mucosal inflammation. However, it has not been clear whether CO effects to colonic mucosal restitution or not. In general, colonic myofibroblast (MF) has been reported to play an important role of colonic epithelial cell restitution via constitutive secretion of TGF-β. In this study, we showed CO (supplied by CO-releasing molecule
    CORM) treated MF conditioned medium enhanced colonic epithelial cell (YAMC) restitution and we determined gene expression in colonic MF treated with CO using microRNA. The microRNA array suggested that miR-710 was significantly reduced in MF by CO treatment and the target gene of miR-710 is determined to fibroblast growth factor (FGF)15. The CO treated MF conditioned medium which FGF15 expression was silenced extinguished the enhancement effect of epithelial cell restitution. Our findings demonstrate that CO treatment to MF increased FGF15 expression via inhibition of miR-710 and FGF15 enhanced colonic epithelial cell restitution. © 2009 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2009.12.035

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    PubMed

  43. Inhibition of Bach1 ameliorates indomethacin-induced intestinal injury in mice. Reviewed

    A. Harusato, Y. Naito, T. Takagi, S. Yamada, K. Mizushima, Y. Hirai, R. Horie, K. Inoue, K. Fukumoto, I. Hirata, T. Omatsu, E. Kishimoto, K. Uchiyama, O. Handa, T. Ishikawa, S. Kokura, H. Ichikawa, A. Muto, K. Igarashi, T. Yoshikawa

    Journal of physiology and pharmacology : an official journal of the Polish Physiological Society   Vol. 60   page: 149 - 154   2009

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    BTB and CNC homolog 1 (Bach1) is a transcriptional repressor of heme oxygenase-1 (HO-1). It plays an important role in the feedback regulation of HO-1 expression, which protects cells from various insults including oxidative stress and inflammatory cytokines. However, the role of Bach1 in intestinal inflammation remains unclear. In this study, the role of Bach1 in intestinal mucosal injury was elucidated using 8-week-old female C57BL/6 (wild-type) and homozygous Bach1-deficient C57BL/6 mice. Intestinal mucosal injuries induced by a single subcutaneous administration of indomethacin were evaluated macroscopically, histologically, and biochemically. Mucosal protein content and chemokine mRNA levels were determined by real-time PCR. Our results showed that the indomethacin-induced intestinal injury was remarkably improved in Bach1-deficient mice. Histological examination showed that the area of injured lesion was decreased in Bach1-deficient mice compared to wild-type mice. Administration of indomethacin induced expression of inflammatory chemokines such as KC, MIP1alpha and MCP1, which was suppressed in Bach1-deficient mice. Myeloperoxidase activity in the intestinal mucosa was also significantly decreased in Bach1-deficient mice. Additionally, Bach1 deficiency enhanced immunopositivity of HO-1 in the intestinal mucosa after indomethacin administration. Disruption of the Bach1 gene thus caused inhibition of mucosal injury, indicating that inhibition of Bach1 may be a novel therapeutic strategy for treating indomethacin-induced intestinal injury.

    Scopus

    PubMed

  44. 胃癌・大腸癌と生活習慣、Metabolic syndromeとの関連に関する検討 Reviewed

    小島 孝雄, 濱口 真英, 加藤 隆弘, 佐藤 寛之, 横溝 千尋, 坂井 宏実, 春里 暁人, 高野 幸彦, 大洞 昭博, 奥田 順一, 井田 和徳, 出口 冨美子

    日本消化器がん検診学会雑誌   Vol. 46 ( 5 ) page: 558 - 566   2008.9

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    総合健診受診者12716名(男性7789名、女性4927名)を対象に、癌と生活習慣、メタボリック症候群(MS)との関係について前向き調査を行い、受診後1年以内に癌と診断された者を健診受診時担癌者とした。その結果、対象者の0.9%・120名(男性87名、女性33名)から癌が報告され、胃癌33名(男性27名、女性6名)、大腸癌27名(男性20名、女性7名)であり、MSは男性13.6%・女性1.2%に認められた。胃癌ではMS(+)0.4%・MS(-)0.3%と差を認めなかったが、大腸癌ではMS(+)0.5%・MS(-)0.2%と有意差を認めた。空腹時高血糖(IFG)(+)では胃癌0.7%、大腸癌0.5%とIFG(-)の胃癌0.2%・大腸癌0.2%より多く認めた。MSの各因子の多変量解析では、胃癌のIFGオッズ比は2.84(P=0.01)と有意であり、大腸癌でもIFGオッズ比は2.58(P=0.037)と有意であった。以上より、胃癌・大腸癌は喫煙・飲酒・コーヒー・運動の四つの生活習慣に有意な関連を認めなかったが、MSは大腸癌において有意な危険因子であり、IFGは胃癌・大腸癌の両者で有意な危険因子であった。

    Other Link: https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2008&ichushi_jid=J04447&link_issn=&doc_id=20080918220002&doc_link_id=10.11404%2Fjsgcs.46.558&url=https%3A%2F%2Fdoi.org%2F10.11404%2Fjsgcs.46.558&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

  45. Helicobacterと内視鏡技術 Helicobacter pylori胃炎の内視鏡診断 Hemoglobin indexによる診断も含めて

    井田 和徳, 加藤 隆弘, 春里 暁人, 小島 孝雄, 奥田 順一, 内山 和彦, 宮田 昌彦, 宮田 史行

    Helicobacter Research   Vol. 11 ( 6 ) page: 520 - 526   2007.12

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    1991年に提唱された新しい胃炎の概念Sydney Systemに対応する内視鏡診断はいまだに確立されていない。われわれは、Helicobacter pylori(H.pylori)感染による胃粘膜の炎症にもとづく所見-(1)胃底腺粘膜のびまん性発赤、(2)同粘膜の集合細静脈の拡張(点状発赤も含む)、(3)胃体部大彎ひだの腫大・蛇行-を診断指標にして検討した。その結果、上記(1)(2)(3)の順に内視鏡診断成績は、感度94.5%,90.4%,96.7%、特異度83.9%,81.7%,69.2%であった。また、びまん性発赤を定量的に評価するHemoglobin index(IHb)では、感度、特異度とも90%であった。これらの成績は、内視鏡疑診例、IHbのグレーゾーン例を除いたものであるが、H.pyloriの一般診断検査にあまり遜色のない成績である。IHb測定を含めたH.pyloriの内視鏡診断はreal timeに、容易に、しかも経費をかけることなく実施できる有用な診断法である。(著者抄録)

    Other Link: https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2007&ichushi_jid=J03103&link_issn=&doc_id=20071210410001&doc_link_id=%2Fae6helib%2F2007%2F001106%2F001%2F0520-0526%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae6helib%2F2007%2F001106%2F001%2F0520-0526%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  46. 【今できる小腸疾患へのアプローチ】小腸疾患の診断におけるVirtual Enteroscopy Reviewed

    加藤 隆弘, 横溝 千尋, 坂井 宏実, 春里 暁人, 濱口 真英, 尾松 達司, 谷口 浩也, 廣瀬 洋一郎, 長縄 聡, 小島 孝雄, 奥田 順一, 井田 和徳

    消化器内視鏡   Vol. 18 ( 11 ) page: 1725 - 1731   2006.11

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    Virtual enteroscopyは、軽微な病変を除けば小腸X線造影検査やカプセル内視鏡検査、ダブルバルーン小腸内視鏡検査から得られる情報を一度に入手でき、Crohn病や憩室性疾患、腸閉塞などの診断に有用な検査法である。他の検査法により得られる画像とのfusion画像の作製など、新たな応用も可能であり、また、MDCT機器のバージョンアップなどにより更なる発展も期待できる。Virtual enteroscopyは、小腸X線造影検査、カプセル内視鏡検査やダブルバルーン小腸内視鏡検査とともに、小腸疾患の診断に積極的に導入していかなければならない検査法である。(著者抄録)

  47. 腸管出血性大腸菌(O157)感染症4例の検討 Reviewed

    今井 昭人, 小山田 裕一, 春里 暁人, 中埜 幸治, 内藤 裕二, 吉田 憲正, 吉川 敏一

    京都医学会雑誌   Vol. 52 ( 1 ) page: 89 - 93   2005.6

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    最近3年間に成人のO157感染症を4例(43歳女,21歳女,62歳女,25歳女)経験し,そのうち1例(43歳女)は溶血性尿毒症症候群(HUS)を合併した.4例とも血性下痢で発症し腹部CTで右側大腸腸管壁の著明な壁肥厚を認めた.便培養は陰性であったが,O157-LPS抗体が陽性と判明しO157感染症と診断した.症例1はHUSを合併し,週3回の血液透析を行い救命できた.症例1は抗生物質が便培養検査前に投与されていたこと,便培養検査までに5日を要したことから陰性になった可能性が示唆されたが,症例2,3,4は下痢発症後4日以内の抗生物質投与前に便培養を行っていたが陰性であった.いずれの症例も救急外来を経由しており,検体の採取から培養開始までに24時間以上要したことが原因の一つと考えられた

  48. A case of Castleman disease arising from lesser sac Reviewed

    Akihito Harusato, Yuji Naito, Takeshi Hattori, Norimasa Yoshida, Akeo Hagiwara, Takeshi Okanoue, Toshikazu Yoshikawa

    Japanese Journal of Gastroenterology   Vol. 101 ( 2 ) page: 168 - 172   2004.2

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MISC 98

  1. Helicobacter pylori感染状況による胃底腺型胃癌の臨床病理学的特徴

    向井 啓起, 土肥 統, 岩井 直人, 落合 都萌子, 山内 克真, 瀬谷 真由子, 福井 勇人, 宮崎 啓, 土井 俊文, 廣瀬 亮平, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    日本消化管学会雑誌   Vol. 8 ( Suppl. ) page: 311 - 311   2024.1

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  2. 表在型食道癌と頭頸部癌の同時重複癌症例における治療戦略

    落合 都萌子, 土肥 統, 岩井 直人, 向井 啓起, 山内 克真, 瀬谷 真由子, 宮崎 啓, 福井 勇人, 廣瀬 亮平, 土井 俊文, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 高木 智久, 石川 剛, 小西 英幸, 伊藤 義人

    日本消化管学会雑誌   Vol. 8 ( Suppl. ) page: 362 - 362   2024.1

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  3. 小腸疾患治療の最前線 小腸脂肪腫に対するEndoscopic Unroofing法

    井上 健, 小林 玲央, 朝枝 興平, 岩井 直人, 廣瀬 亮平, 土井 俊文, 春里 暁人, 土肥 統, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 内藤 裕二, 伊藤 義人

    日本消化管学会雑誌   Vol. 8 ( Suppl. ) page: 208 - 208   2024.1

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  4. 家族性大腸腺腫症患者の十二指腸上皮性腫瘍に対する長期治療成績

    宮崎 啓, 土肥 統, 岩井 直人, 向井 啓起, 落合 都萌子, 瀬谷 真由子, 山内 克真, 福井 勇人, 土井 俊文, 廣瀬 亮平, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    日本消化管学会雑誌   Vol. 8 ( Suppl. ) page: 324 - 324   2024.1

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  5. 十二指腸Cold Snare Polypectomyの術中出血に対する吸収性局所止血材の有用性

    瀬谷 真由子, 土肥 統, 落合 都萌子, 向井 啓起, 山内 克真, 宮崎 啓, 福井 勇人, 岩井 直人, 廣瀬 亮平, 土井 俊文, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    日本消化管学会雑誌   Vol. 8 ( Suppl. ) page: 293 - 293   2024.1

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  6. Conventional versus underwater endoscopic resection for superficial non-ampullary duodenal epithelial tumours. International journal

    Hajime Miyazaki, Osamu Dohi, Tsugitaka Ishida, Mayuko Seya, Katsuma Yamauchi, Hayato Fukui, Takeshi Yasuda, Takuma Yoshida, Naoto Iwai, Toshifumi Doi, Ryohei Hirose, Ken Inoue, Akihito Harusato, Naohisa Yoshida, Kazuhiko Uchiyama, Tomohisa Takagi, Takeshi Ishikawa, Hideyuki Konishi, Yukiko Morinaga, Mitsuo Kishimoto, Yuji Naito, Yoshito Itoh

    Japanese journal of clinical oncology     2023.10

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    BACKGROUND AND OBJECTIVE: Several endoscopic resection methods have been developed as less invasive treatments for superficial non-ampullary duodenal epithelial tumours. This study aimed to compare outcomes of conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours, including resection depth and rate of the muscularis mucosa contained under the lesion. METHODS: This single-centre retrospective cohort study conducted from January 2009 to December 2021 enrolled patients who underwent conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours and investigated their clinicopathological outcomes using propensity score matching. RESULTS: Of the 285 superficial non-ampullary duodenal epithelial tumours, 98 conventional endoscopic mucosal resections and 187 underwater endoscopic mucosal resections were included. After propensity score matching, 64 conventional endoscopic mucosal resections and 64 underwater endoscopic mucosal resections were analysed. The R0 resection rate was significantly higher in underwater endoscopic mucosal resection cases than in conventional endoscopic mucosal resection cases (70.3% vs. 50.0%; P = 0.030). In the multivariate analysis, a lesion diameter > 10 mm (odds ratio 7.246; P = 0.001), being in the 1st-50th treatment period (odds ratio 3.405; P = 0.008), and undergoing conventional endoscopic mucosal resection (odds ratio 3.617; P = 0.016) were associated with RX/R1 resection. Furthermore, in underwater endoscopic mucosal resection cases, the R0 rate was significantly higher for lesions diameter ≤10 mm than >10 mm, and was significantly higher in the 51st-treatment period than in the 1st-50th period. Conventional endoscopic mucosal resection and underwater endoscopic mucosal resection cases showed no significant difference in resection depth and muscularis mucosa containing rate. CONCLUSIONS: Underwater endoscopic mucosal resection may be more acceptable than conventional endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours ≤ 10 mm. A steep early learning curve may be acquired for underwater endoscopic mucosal resection. Large multicentre prospective studies need to be conducted to confirm the effectiveness of underwater endoscopic mucosal resection.

    DOI: 10.1093/jjco/hyad145

    PubMed

  7. 家族性大腸腺腫症に併発する十二指腸上皮性腫瘍に対する積極的内視鏡切除の現状

    宮崎 啓, 土肥 統, 向井 啓起, 落合 都萌子, 瀬谷 真由子, 山内 克真, 福井 勇人, 安田 剛士, 岩井 直人, 土井 俊文, 廣瀬 亮平, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    Gastroenterological Endoscopy   Vol. 65 ( Suppl.2 ) page: 1993 - 1993   2023.10

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  8. 非乳頭部十二指腸上皮性腫瘍に対するESDとLECSの短期・長期予後成績

    瀬谷 真由子, 土肥 統, 落合 都萌子, 向井 啓起, 山内 克真, 宮崎 啓, 福井 勇人, 岩井 直人, 廣瀬 亮平, 土井 俊文, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    Gastroenterological Endoscopy   Vol. 65 ( Suppl.2 ) page: 1992 - 1992   2023.10

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  9. 表在型咽頭上皮性腫瘍に対するESDとTOVSとの治療成績の比較検討

    落合 都萌子, 岩井 直人, 土肥 統, 向井 啓起, 瀬谷 真由子, 山内 克真, 宮崎 啓, 福井 勇人, 廣瀬 亮平, 土井 俊文, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    Gastroenterological Endoscopy   Vol. 65 ( Suppl.2 ) page: 1963 - 1963   2023.10

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  10. 早期胃癌ESD後の創部に対するクリップ縫縮の工夫

    福井 勇人, 土肥 統, 瀬谷 真由子, 山内 克真, 宮崎 啓, 安田 剛士, 岩井 直人, 土井 俊文, 廣瀬 亮平, 井上 健, 春里 暁人, 吉田 直人, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    Gastroenterological Endoscopy   Vol. 65 ( Suppl.2 ) page: 1985 - 1985   2023.10

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  11. 内視鏡的生検後に自然消退し免疫応答の関与が疑われた大腸T1癌の一例

    岡野 史弥, 吉田 直久, 森永 友紀子, 安藤 貴志, 小林 玲央, 岩井 直人, 土井 俊文, 井上 健, 廣瀬 亮平, 春里 暁人, 土肥 統, 石川 剛, 内山 和彦, 高木 智久, 小西 英幸, 伊藤 義人

    日本消化器病学会近畿支部例会プログラム・抄録集   Vol. 119回   page: 103 - 103   2023.9

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  12. 非飲酒・非喫煙者に発生する食道扁平上皮癌の遺伝子学的特徴 C-CATデータベースからの知見(Genetic Characteristics of Esophageal Squamous Cell Carcinoma in Non-Drinkers and Non-Smokers: C-CAT Database Findings)

    森田 竜一, 石川 剛, 土井 俊文, 伊谷 純一郎, 曽根 大暉, 岩井 直人, 廣瀬 亮平, 井上 健, 土肥 統, 春里 暁人, 吉田 直久, 内山 和彦, 高木 智久, 小西 英幸, 伊藤 義人

    日本癌学会総会記事   Vol. 82回   page: 831 - 831   2023.9

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  13. 腎癌術後経過観察中に合併した膵神経内分泌腫瘍の1例

    向井 愛純, 三宅 隼人, 片岡 星太, 岩井 直人, 瀬古 裕也, 廣瀬 亮平, 土井 俊文, 井上 健, 土肥 統, 春里 暁人, 吉田 直久, 森口 理久, 十亀 義生, 内山 和彦, 石川 剛, 山口 寛二, 高木 智久, 小西 英幸, 伊藤 義人

    日本消化器病学会近畿支部例会プログラム・抄録集   Vol. 119回   page: 95 - 95   2023.9

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  14. 後方視的に発見時までの長期間の膵形態変化が画像的に追跡できた膵尾部癌の1例

    加藤 大貴, 三宅 隼人, 片岡 星太, 岩井 直人, 瀬古 裕也, 廣瀬 亮平, 土井 俊文, 井上 健, 土肥 統, 春里 暁人, 吉田 直久, 森口 理久, 十亀 義生, 内山 和彦, 石川 剛, 山口 寛二, 高木 智久, 小西 英幸, 伊藤 義人

    日本消化器病学会近畿支部例会プログラム・抄録集   Vol. 119回   page: 87 - 87   2023.9

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  15. H.pylori除菌後の諸問題 胃底腺型胃癌のHelicobacter pylori感染状態から見た臨床病理学的特徴

    向井 啓起, 土肥 統, 落合 都萌子, 山内 克真, 瀬谷 真由子, 福井 勇人, 宮崎 啓, 岩井 直人, 土井 俊文, 廣瀬 亮平, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    日本ヘリコバクター学会学術集会プログラム・抄録集   Vol. 29回   page: 78 - 78   2023.6

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  16. H.pylori除菌後の諸問題 胃底腺型胃癌のHelicobacter pylori感染状態から見た臨床病理学的特徴

    向井 啓起, 土肥 統, 落合 都萌子, 山内 克真, 瀬谷 真由子, 福井 勇人, 宮崎 啓, 岩井 直人, 土井 俊文, 廣瀬 亮平, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    日本ヘリコバクター学会学術集会プログラム・抄録集   Vol. 29回   page: 78 - 78   2023.6

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  17. 胃ESDにおけるトレイニーの処置完遂に関係する因子の検討

    福井 勇人, 土肥 統, 瀬谷 真由子, 山内 克真, 宮崎 啓, 安田 剛士, 岩井 直人, 廣瀬 亮平, 土井 俊文, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    Gastroenterological Endoscopy   Vol. 65 ( Suppl.1 ) page: 899 - 899   2023.4

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  18. 胃・十二指腸ESDにおける高難度症例への対処 胃穹窿部早期癌に対する腹臥位変換ESDの安全性と有用性

    福井 勇人, 土肥 統, 瀬谷 真由子, 山内 克真, 宮崎 啓, 安田 剛士, 岩井 直人, 土井 俊文, 廣瀬 亮平, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    日本胃癌学会総会記事   Vol. 95回   page: 227 - 227   2023.2

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  19. 十二指腸表在腫瘍の診断と治療の最前線 十二指腸表在型上皮性腫瘍に対するESDとLECSの短期・長期予後成績に関する検討

    瀬谷 真由子, 土肥 統, 山内 克真, 宮崎 啓, 福井 勇人, 安田 剛士, 廣瀬 亮平, 土井 俊文, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    日本消化管学会雑誌   Vol. 7 ( Suppl. ) page: 194 - 194   2023.1

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  20. 食道胃接合部癌診療の最前線 食道胃接合部におけるBarret腺癌と噴門部腺癌の臨床病理学的特徴

    山内 克真, 土肥 統, 瀬谷 真由子, 福井 勇人, 宮崎 啓, 安田 剛士, 廣瀬 亮平, 土井 俊文, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    日本消化管学会雑誌   Vol. 7 ( Suppl. ) page: 158 - 158   2023.1

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  21. 背景胃粘膜の応じた早期胃癌の診断と治療 Helicobacter pylori除菌後発見胃癌のリスク因子の評価 多施設共同前向き観察研究

    福井 勇人, 土肥 統, 高山 峻, 瀬谷 真由子, 山内 克真, 宮崎 啓, 安田 剛士, 土井 俊文, 廣瀬 亮平, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    日本消化管学会雑誌   Vol. 7 ( Suppl. ) page: 149 - 149   2023.1

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  22. 肝粘液性嚢胞性腫瘍(MCN)や胆管内乳頭状腫瘍(IPNB)との鑑別が必要で、胆管過誤腫様変化が併存した腫瘤形成型胆管細胞癌の一例

    有村 勇哉, 小西 英幸, 谷口 昌史, 三宅 隼人, 土井 俊文, 廣瀬 亮平, 井上 健, 土肥 統, 春里 暁人, 吉田 直久, 内山 和彦, 十亀 義生, 石川 剛, 高木 智久, 保田 宏明, 田中 顕之, 伊藤 義人

    日本消化器病学会近畿支部例会プログラム・抄録集   Vol. 118回   page: 76 - 76   2023.1

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  23. 消化管診断学【内視鏡診断および病理診断の最先端】多発胃癌・神経内分泌腫瘍を生じた自己免疫性胃炎例の背景粘膜の特徴

    安田 剛士, 土肥 統, 瀬谷 真由子, 山内 克真, 福井 勇人, 宮崎 啓, 廣瀬 亮平, 土井 俊文, 井上 健, 春里 暁人, 吉田 直久, 石川 剛, 内山 和彦, 高木 智久, 小西 英幸, 伊藤 義人

    日本消化管学会雑誌   Vol. 7 ( Suppl. ) page: 121 - 121   2023.1

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  24. 慢性便秘症の病態・診断・治療の最前線 酸分泌抑制剤投与に伴う便秘と腸内細菌叢の変化

    土肥 統, 安田 剛士, 瀬谷 真由子, 山内 克真, 福井 勇人, 宮崎 啓, 廣瀬 亮平, 土井 俊文, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 高木 智久, 石川 剛, 小西 英幸, 内藤 裕二, 伊藤 義人

    日本消化管学会雑誌   Vol. 7 ( Suppl. ) page: 204 - 204   2023.1

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  25. Risk and prognostic factors of invasive gastric cancer detection during surveillance endoscopy: a multi-institutional cross-sectional study. International journal

    Takeshi Yasuda, Osamu Dohi, Shinya Yamada, Tsugitaka Ishida, Naoto Iwai, Hitoshi Hongo, Kei Terasaki, Makoto Tanaka, Nobuhisa Yamada, Kazuhiro Kamada, Ryusuke Horie, Akihito Harusato, Yusuke Horii, Shun Takayama, Keika Zen, Atsushi Majima, Naoki Mizuno, Takayuki Motoyoshi, Nobuaki Yagi, Yuji Naito, Yoshito Itoh

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society   Vol. 35 ( 5 ) page: 592 - 602   2022.12

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    OBJECTIVES: Esophagogastroduodenoscopy is important for the detection of curable gastric cancer (GC). However, there are no appropriate surveillance data during routine endoscopic inspections. This study aimed to clarify the risk factors of pT1b- or deeper-GC detection during surveillance endoscopy. METHODS: This was a retrospective, multicenter, cross-sectional study conducted in 15 Japanese hospitals. We retrospectively analyzed patients with GC who had previously undergone surveillance endoscopy at each institution from January 2014 to March 2020. Patients who had undergone gastrectomy, non-infection of Helicobacter pylori (Hp), and those with intervals < 3 months or >10 years from a previous endoscopy were excluded. RESULTS: In total, 1085 patients with GCs detected during surveillance endoscopy were enrolled. The multivariate logistic analysis revealed that current Hp infection (odds ratio [OR], 2.18; 95% confidence interval [CI] 1.50-3.16) and a surveillance interval of >1.5 years (OR, 1.96; 95% CI, 1.35-2.84) were independent risk factors for pT1b- or deeper-GC. The 5-year disease-specific survival (5y-DSS) rate of GC was significantly lower in patients with surveillance interval of >1.5 years than in those with surveillance interval of ≤1.5 years (93.7% vs. 98.3%, P <0.001). Similarly, the 5y-DSS rate of GC was significantly lower in patients with active Hp infection than in those without (93.7% vs. 99.4%, P <0.001). CONCLUSION: In this study, a surveillance interval of >1.5 years and current Hp infection were independent risk factors for detecting pT1b- or deeper-GC. Additionally, these factors were poor prognostic factors of the detected GC during surveillance endoscopy.

    DOI: 10.1111/den.14492

    PubMed

  26. Obscure gastrointestinal bleeding from a large jejunal lipoma treated using an endoscopic unroofing technique with double balloon enteroscopy: a case study.

    Reo Kobayashi, Ken Inoue, Ryohei Hirose, Toshifumi Doi, Akihito Harusato, Osamu Dohi, Naohisa Yoshida, Kazuhiko Uchiyama, Takeshi Ishikawa, Tomohisa Takagi, Hiroaki Yasuda, Hideyuki Konishi, Yukiko Morinaga, Yoshito Itoh

    Clinical journal of gastroenterology   Vol. 16 ( 1 ) page: 32 - 38   2022.11

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    Small intestinal lipomas are rare, but may cause obscure gastrointestinal bleeding. The endoscopic unroofing technique excises only the upper third of the lipoma and allows both histological confirmation and complete treatment with minimal risk of perforation. We present a rare case of obscure gastrointestinal bleeding caused by a jejunal lipoma. A 75-year-old man on antiplatelet therapy presented to our department with melena and anemia. Computed tomography revealed he had a 45-mm jejunal submucosal tumor with fat attenuation. Endoscopic resection using an endoscopic unroofing technique with double balloon enteroscopy was successfully performed. The tumor was confirmed to be a lipoma.

    DOI: 10.1007/s12328-022-01724-3

    PubMed

  27. 粘膜下腫瘍様の形態を呈した進行食道扁平上皮癌の1例

    辻 まどか, 山内 克真, 井上 健, 廣瀬 亮平, 土井 俊文, 春里 暁人, 土肥 統, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 保田 宏明, 小西 英幸, 中野 貴博, 山田 真也, 戸祭 直也, 伊藤 義人

    日本消化器内視鏡学会近畿支部例会プログラム・抄録集   Vol. 109回   page: 81 - 81   2022.11

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  28. Association Between the Cool Temperature-dependent Suppression of Colonic Peristalsis and Transient Receptor Potential Melastatin 8 Activation in Both a Randomized Clinical Trial and an Animal Model. International journal

    Satoshi Sugino, Ken Inoue, Reo Kobayashi, Ryohei Hirose, Toshifumi Doi, Akihito Harusato, Osamu Dohi, Naohisa Yoshida, Kazuhiko Uchiyama, Takeshi Ishikawa, Tomohisa Takagi, Hiroaki Yasuda, Hideyuki Konishi, Yasuko Hirai, Katsura Mizushima, Yuji Naito, Toshifumi Tsuji, Takashi Okuda, Keizo Kagawa, Makoto Tominaga, Yoshito Itoh

    Journal of neurogastroenterology and motility   Vol. 28 ( 4 ) page: 693 - 705   2022.10

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    Background/Aims: Several studies have assessed the effect of cool temperature on colonic peristalsis. Transient receptor potential melastatin 8 (TRPM8) is a temperature-sensitive ion channel activated by mild cooling expressed in the colon. We examined the antispasmodic effect of cool temperature on colonic peristalsis in a prospective, randomized, single-blind trial and based on the video imaging and intraluminal pressure of the proximal colon in rats and TRPM8-deficient mice. Methods: In the clinical trial, we randomly assigned a total of 94 patients scheduled to undergo colonoscopy to 2 groups: the mildly cool water (n = 47) and control (n = 47) groups. We used 20 mL of 15°C water for the mildly cool water. The primary outcome was the proportion of subjects with improved peristalsis after treatment. In the rodent proximal colon, we evaluated the intraluminal pressure and performed video imaging of the rodent proximal colon with cool water administration into the colonic lumen. Clinical trial registry website (Trial No. UMIN-CTR; UMIN000030725). Results: In the randomized controlled trial, after treatment, the proportion of subjects with no peristalsis with cool water was significantly higher than that in the placebo group (44.7% vs 23.4%; P < 0.05). In the rodent colon model, cool temperature water was associated with a significant decrease in colonic peristalsis through its suppression of the ratio of peak frequency (P < 0.05). Cool temperature-treated TRPM8-deficient mice did not show a reduction in colonic peristalsis compared with wild-type mice. Conclusion: For the first time, this study demonstrates that cool temperature-dependent suppression of colonic peristalsis may be associated with TRPM8 activation.

    DOI: 10.5056/jnm21198

    PubMed

  29. SARS-CoV-2ワクチン接種により潰瘍性大腸炎の再燃・CMV腸炎の発症を繰り返した一例

    山内 克真, 小西 英幸, 廣瀬 亮平, 土井 俊文, 井上 健, 春里 暁人, 土肥 統, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 伊藤 義人

    日本消化器病学会近畿支部例会プログラム・抄録集   Vol. 117回   page: 102 - 102   2022.10

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  30. 内視鏡検査時における環境中の新型コロナウイルス汚染状況の正確な評価方法構築

    宮崎 啓, 廣瀬 亮平, 土井 俊文, 井上 健, 春里 暁人, 土肥 統, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    Gastroenterological Endoscopy   Vol. 64 ( Suppl.2 ) page: 2089 - 2089   2022.10

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  31. 胃炎の京都分類を用いたスコアリングシステムの構築と除菌後発見胃癌のリスク評価

    山内 克真, 土肥 統, 北江 博晃, 瀬谷 真由子, 宮崎 啓, 福井 勇人, 安田 剛士, 廣瀬 亮平, 土井 俊文, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    Gastroenterological Endoscopy   Vol. 64 ( Suppl.2 ) page: 2072 - 2072   2022.10

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  32. 十二指腸乳頭部進展を伴う表在性十二指腸上皮性腫瘍に対するESDの工夫

    瀬谷 真由子, 土肥 統, 山内 克真, 宮崎 啓, 福井 勇人, 安田 剛士, 廣瀬 亮平, 土井 俊文, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    Gastroenterological Endoscopy   Vol. 64 ( Suppl.2 ) page: 2108 - 2108   2022.10

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  33. 切除不能肝門部領域胆管癌に対する留置方法別プラスチックステント開存期間の検討

    渡邊 直人, 土井 俊文, 小西 英幸, 森田 竜一, 窪田 真理子, 榊田 智喜, 片岡 星太, 三宅 隼人, 廣瀬 亮平, 井上 健, 春里 暁人, 土肥 統, 吉田 直久, 内山 和彦, 高木 智久, 石川 剛, 伊藤 義人

    Gastroenterological Endoscopy   Vol. 64 ( Suppl.2 ) page: 2155 - 2155   2022.10

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  34. FDG-PETで集積亢進を呈する食道平滑筋腫に対して経口内視鏡的粘膜下腫瘍核出術を施行した一例

    澤 貴幸, 土肥 統, 三宅 隼人, 山内 克真, 瀬谷 真由子, 宮崎 啓, 福井 勇人, 安田 剛士, 吉田 拓馬, 石田 紹敬, 廣瀬 亮平, 土井 俊文, 井上 建, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 保田 宏明, 小西 秀幸, 伊藤 義人

    日本消化器内視鏡学会近畿支部例会プログラム・抄録集   Vol. 108回   page: 77 - 77   2022.6

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  35. A case of endoscopic submucosal dissection for neuroendocrine carcinoma of the esophagus with invasion to the muscularis mucosae.

    Hayato Fukui, Osamu Dohi, Hajime Miyazaki, Takeshi Yasuda, Takuma Yoshida, Tsugitaka Ishida, Toshifumi Doi, Ryohei Hirose, Ken Inoue, Akihito Harusato, Naohisa Yoshida, Kazuhiko Uchiyama, Takeshi Ishikawa, Tomohisa Takagi, Hideyuki Konishi, Yukiko Morinaga, Yoshito Itoh

    Clinical journal of gastroenterology   Vol. 15 ( 2 ) page: 339 - 344   2022.4

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    Neuroendocrine carcinoma (NEC) of the esophagus at early-stage is very rare due to its rapidly progression. Here, we reported a case of esophageal NEC at early stage treated with endoscopic submucosal dissection (ESD). A 63-year-old man underwent esophagogastroduodenoscopy (EGD) and a lesion was detected in the thoracic esophagus. The preoperative diagnosis was squamous cell carcinoma (SCC) based on magnifying endoscopy; however, the pathological diagnosis was NEC with an invasion of muscularis mucosa accompanied by lymphovascular invasion. Adjuvant chemoradiotherapy was recommended after ESD; however, the patient did not accept additional treatments. The patient was alive with no recurrence 15 months after ESD. In this case, there were three malignant components among SCC, NEC, and adenocarcinoma with transitional areas among each component in the superficial part of the lesion.

    DOI: 10.1007/s12328-022-01595-8

    PubMed

  36. 乳頭部および乳頭近傍に存在する表在性十二指腸上皮性腫瘍に対するESDの安全性と有用性

    福井 勇人, 土肥 統, 伊藤 義人, 瀬谷 真由子, 山内 克真, 宮崎 啓, 安田 剛士, 吉田 拓馬, 石田 紹敬, 廣瀬 亮平, 土井 俊文, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸

    Gastroenterological Endoscopy   Vol. 64 ( Suppl.1 ) page: 737 - 737   2022.4

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  37. 胃底腺型胃癌のHelicobacter pylori感染状況による臨床病理学的特徴

    福井 勇人, 土肥 統, 宮崎 啓, 安田 剛士, 吉田 拓馬, 石田 紹敬, 土井 俊文, 廣瀬 亮平, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    日本消化器病学会雑誌   Vol. 119 ( 臨増総会 ) page: A336 - A336   2022.3

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  38. 胃底腺型胃癌のHelicobacter pylori感染状況による臨床病理学的特徴

    福井 勇人, 土肥 統, 宮崎 啓, 安田 剛士, 吉田 拓馬, 石田 紹敬, 土井 俊文, 廣瀬 亮平, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    日本消化器病学会雑誌   Vol. 119 ( 臨増総会 ) page: A336 - A336   2022.3

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  39. Clinicopathological features of gastric cancer detected in Helicobacter pylori eradicated stomach-Comparison between eradication therapy and spontaneous eradication-

    福井勇人, 土肥統, 宮崎啓, 安田剛士, 吉田拓馬, 石田紹敬, 土井俊文, 廣瀬亮平, 井上健, 春里暁人, 吉田直久, 内山和彦, 石川剛, 高木智久, 小西英幸, 伊藤義人

    日本消化管学会雑誌(CD-ROM)   Vol. 6 ( Suppl. ) page: 150 - 150   2022.1

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    J-GLOBAL

  40. ピロリ除菌後胃癌、未感染胃癌の問題点と研究 Helicobacter pylori既感染胃癌の臨床病理学的特徴 除菌療法の有無による比較

    福井 勇人, 土肥 統, 宮崎 啓, 安田 剛士, 吉田 拓馬, 石田 紹敬, 土井 俊文, 廣瀬 亮平, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    日本消化管学会雑誌   Vol. 6 ( Suppl. ) page: 150 - 150   2022.1

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  41. 十二指腸腫瘍内視鏡治療における工夫 表在性十二指腸非乳頭部腫瘍に対する内視鏡治療後浸水下予防縫縮

    石田 紹敬, 土肥 統, 福井 勇人, 宮崎 啓, 安田 剛士, 吉田 拓馬, 廣瀬 亮平, 土井 俊文, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    日本消化管学会雑誌   Vol. 6 ( Suppl. ) page: 176 - 176   2022.1

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  42. 食道疾患に対する内視鏡治療の工夫 広範囲食道ESD後ステロイド嚥下療法の狭窄予防効果

    安田 剛士, 土肥 統, 福井 勇人, 宮崎 啓, 吉田 拓馬, 石田 紹敬, 廣瀬 亮平, 土井 俊文, 井上 健, 春里 暁人, 吉田 直久, 石川 剛, 内山 和彦, 高木 智久, 小西 英幸, 伊藤 義人

    日本消化管学会雑誌   Vol. 6 ( Suppl. ) page: 161 - 161   2022.1

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  43. Efficacy of topical steroid therapy for preventing esophageal stricture after 3/4 round or more circumferential esophageal ESD

    安田剛士, 土肥統, 福井勇人, 宮崎啓, 吉田拓馬, 石田紹敬, 廣瀬亮平, 土井俊文, 井上健, 春里暁人, 吉田直久, 石川剛, 内山和彦, 高木智久, 小西英幸, 伊藤義人

    日本消化管学会雑誌(CD-ROM)   Vol. 6 ( Suppl. ) page: 161 - 161   2022.1

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  44. Efficacy of scissors-type knife for endoscopic submucosal dissection of gastric cancer in the remnant stomach

    宮崎啓, 土肥統, 福井勇人, 安田剛士, 吉田拓馬, 石田紹敬, 廣瀬亮平, 土井俊文, 井上健, 春里暁人, 吉田直久, 内山和彦, 石川剛, 高木智久, 小西英幸, 伊藤義人

    日本消化管学会雑誌(CD-ROM)   Vol. 6 ( Suppl. ) page: 167 - 167   2022.1

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  45. 胃腫瘍内視鏡治療における工夫 残胃癌に対するハサミ型ナイフを用いた内視鏡的粘膜下層剥離術の有用性

    宮崎 啓, 土肥 統, 福井 勇人, 安田 剛士, 吉田 拓馬, 石田 紹敬, 廣瀬 亮平, 土井 俊文, 井上 健, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 小西 英幸, 伊藤 義人

    日本消化管学会雑誌   Vol. 6 ( Suppl. ) page: 167 - 167   2022.1

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  46. Mucosal defect closure in underwater conditions after endoscopic treatments for superficial non-ampullary duodenal epithelial tumors

    石田紹敬, 土肥統, 福井勇人, 宮崎啓, 安田剛士, 吉田拓馬, 廣瀬亮平, 土井俊文, 井上健, 春里暁人, 吉田直久, 内山和彦, 石川剛, 高木智久, 小西英幸, 伊藤義人

    日本消化管学会雑誌(CD-ROM)   Vol. 6 ( Suppl. ) page: 176 - 176   2022.1

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    J-GLOBAL

  47. 乳頭部および乳頭近傍に存在する表在性十二指腸上皮性腫瘍に対するESDの安全性と有用性

    福井勇人, 土肥統, 伊藤義人, 瀬谷真由子, 山内克真, 宮崎啓, 安田剛士, 吉田拓馬, 石田紹敬, 廣瀬亮平, 土井俊文, 井上健, 春里暁人, 吉田直久, 内山和彦, 石川剛, 高木智久, 小西英幸

    Gastroenterological Endoscopy (Web)   Vol. 64 ( Supplement1 )   2022

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  48. Hepatic phaseからBiliary phaseまで経過が追えた肝蛭症の一例

    岡野史弥, 春里暁人, 春里暁人, 竹谷祐栄, 石破博, 石破博, 福居顕文, 尾松達司, 岡山哲也, 堅田和弘, 沖田美香, 徳田文太, 佐藤修, 井上健, 土肥統, 井村徹也, 高木智久, 伊藤義人

    日本消化器病学会近畿支部例会プログラム・抄録集   Vol. 116th   2022

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  49. Endoscopic Submucosal Dissection for Early Gastric Cancer in Patients Aged 85 Years Old or Older Is Associated with a Good Prognosis Compared to Conservative Treatment without Any Invasive Procedure. International journal

    Shinya Yamada, Osamu Dohi, Akihito Harusato, Naoto Iwai, Ryusuke Horie, Takeshi Yasuda, Nobuhisa Yamada, Yusuke Horii, Atsushi Majima, Keika Zen, Hiroyuki Kimura, Nobuaki Yagi, Yuji Naito, Yoshito Itoh

    Digestion   Vol. 103 ( 5 ) page: 386 - 396   2022

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    INTRODUCTION: Studies have reported the feasibility of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in elderly people with respect to both short- and long-term outcomes. As the elderly population in society increases, the requirement for managing super-elderly patients aged ≥85 years with EGC will also increase. This study aims to identify the long-term clinical outcomes of ESD for clinical T1N0 EGC in patients aged ≥85 years. METHODS: A total of 370 consecutive patients aged ≥85 years with clinical T1N0 EGC who were managed in 11 institutions were reviewed retrospectively. On the basis of treatment strategy, we compared the overall survival (OS) and disease-specific survival (DSS) after performing propensity score-matched analysis between patients undergoing ESD (ESD group) and those not undergoing treatment (conservative treatment group). The potential prognostic factors were also investigated in the propensity score-matched patients. RESULTS: After propensity score matching, we found that the 3-year OS and DSS rates were significantly higher in the ESD group than in the conservative treatment group (OS, 82.2% vs. 50.5%; p < 0.001; DSS, 100% vs. 80.1%; p = 0.008). Furthermore, ESD was identified as a significant factor for prolonged OS, whereas Charlson comorbidity index (CCI) ≥3 and prognostic nutritional index (PNI) <36.2 were associated with reduced OS. CONCLUSION: ESD was associated with improved OS in patients with clinical T1N0 EGC aged ≥85 years compared with the absence of treatment. Furthermore, CCI and PNI were helpful for patient selection.

    DOI: 10.1159/000525422

    PubMed

  50. 内視鏡検査時における環境中の新型コロナウイルス汚染状況の正確な評価方法構築

    宮崎啓, 廣瀬亮平, 土井俊文, 井上健, 春里暁人, 土肥統, 吉田直久, 内山和彦, 石川剛, 高木智久, 小西英幸, 伊藤義人

    Gastroenterological Endoscopy (Web)   Vol. 64 ( Supplement2 )   2022

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  51. 胃底腺型胃癌のHelicobacter pylori感染状況による臨床病理学的特徴

    福井勇人, 土肥統, 宮崎啓, 安田剛士, 吉田拓馬, 石田紹敬, 土井俊文, 廣瀬亮平, 井上健, 春里暁人, 吉田直久, 内山和彦, 石川剛, 高木智久, 小西英幸, 伊藤義人

    日本消化器病学会雑誌(Web)   Vol. 119   2022

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  52. 残胃癌に対する内視鏡的粘膜下層剥離術の有用性・治療困難因子の検討-多施設共同研究

    山内克真, 土肥統, 伊藤義人, 水野直樹, 寺崎慶, 岩井直人, 間嶋淳, 堀江隆介, 山田真也, 春里暁人, 全圭夏, 元好貴之, 堀居雄介

    Gastroenterological Endoscopy (Web)   Vol. 64 ( Supplement1 )   2022

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  53. 十二指腸乳頭部腫瘍に対する浸水下内視鏡的乳頭切除術の実際

    森田竜一, 土井俊文, 伊藤義人, 渡邊直人, 榊田智喜, 片岡星太, 三宅隼人, 廣瀬亮平, 井上健, 土肥統, 春里暁人, 吉田直久, 内山和彦, 十亀義生, 石川剛, 石川剛, 高木智久, 保田宏明, 小西英幸

    Gastroenterological Endoscopy (Web)   Vol. 64 ( Supplement1 )   2022

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  54. 感染性腸炎との鑑別を要した成人発症IgA血管炎の一例

    澤 貴幸, 井上 健, 三宅 隼人, 廣瀬 亮平, 土井 俊文, 土肥 統, 春里 暁人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 保田 宏明, 小西 英幸, 今本 栄子, 伊藤 義人

    日本消化器内視鏡学会近畿支部例会プログラム・抄録集   Vol. 107回   page: 110 - 110   2021.12

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  55. 胆管内乳頭状腫瘍に対して経口胆道鏡を施行した一例

    堂阪 啓起, 朝枝 興平, 土井 俊文, 井上 健, 十亀 義生, 三宅 隼人, 廣瀬 亮平, 土肥 統, 春里 曉人, 吉田 直久, 内山 和彦, 石川 剛, 高木 智久, 保田 宏明, 小西 英幸, 伊藤 義人

    日本消化器病学会近畿支部例会プログラム・抄録集   Vol. 115回   page: 75 - 75   2021.9

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    J-GLOBAL

  56. Improved Visibility of Early Gastric Cancer after Successful Helicobacter pylori Eradication with Image-Enhanced Endoscopy: A Multi-Institutional Study Using Video Clips. International journal

    Shinya Matsumura, Osamu Dohi, Nobuhisa Yamada, Akihito Harusato, Takeshi Yasuda, Takuma Yoshida, Tsugitaka Ishida, Yuka Azuma, Hiroaki Kitae, Toshifumi Doi, Ryohei Hirose, Ken Inoue, Naohisa Yoshida, Kazuhiro Kamada, Kazuhiko Uchiyama, Tomohisa Takagi, Takeshi Ishikawa, Hideyuki Konishi, Yukiko Morinaga, Mitsuo Kishimoto, Nobuaki Yagi, Yuji Naito, Yoshito Itoh

    Journal of clinical medicine   Vol. 10 ( 16 )   2021.8

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    The visibility and diagnostic accuracy of early gastric cancer (EGC) after Helicobacter pylori (HP) eradication have been reported to improve using image-enhanced endoscopy (IEE) compared with white light imaging (WLI). The present study clarified the appropriate IEE for the detection and diagnosis of EGC in clinical settings. This prospective and cross-sectional study evaluated the visibility of EGC and endoscopic findings of gastric mucosa after successful HP eradication (n = 31) using videos with WLI and IEE. Three endoscopists evaluated high-definition videos in a randomized order. The mean visibility scores (MVSs) on linked color imaging (LCI) for atrophic border, intestinal metaplasia, map-like redness, and EGC were the highest among each modality (3.87 ± 0.34, 3.82 ± 0.49, 3.87 ± 0.50, and 3.35 ± 0.92, respectively). The MVSs with blue laser imaging (BLI) were highest for magnifying view of the demarcation line (DL), microsurface pattern (MSP), and microvascular pattern (MVP) for EGC (3.77 ± 0.49, 3.94 ± 0.25, and 3.92 ± 0.34, respectively). LCI had the highest visibility among findings of gastric mucosa and EGC after HP eradication, and BLI had the highest visibility of MVP, MSP, and DL in magnifying observation. These results suggest that LCI observation in the entire stomach and further magnifying BLI are the best methods for detecting and diagnosing EGCs after HP eradication, respectively.

    DOI: 10.3390/jcm10163649

    PubMed

  57. Prognostic risk factors associated with esophageal squamous cell carcinoma patients undergoing endoscopic submucosal dissection: a multi-center cohort study. International journal

    Naoto Iwai, Osamu Dohi, Shinya Yamada, Akihito Harusato, Ryusuke Horie, Takeshi Yasuda, Nobuhisa Yamada, Yusuke Horii, Atsushi Majima, Keika Zen, Hiroyuki Kimura, Nobuaki Yagi, Yuji Naito, Yoshito Itoh

    Surgical endoscopy   Vol. 36 ( 4 ) page: 2279 - 2289   2021.4

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    BACKGROUND: Long-term outcomes of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) have not been assessed in a large, multicenter cohort. We aimed to evaluate long-term outcomes of ESD for ESCC in a real-world setting. METHODS: We retrospectively recruited 659 patients who underwent ESD for ESCC at ten institutions from January 2007 to December 2015. Of these, 566 patients were analyzed and classified into three groups according to the pathologic invasion depth after ESD: epithelium/lamina propria mucosa (EP/LPM group: 454 patients), muscularis mucosa/submucosa invasion ≤ 200 μm below the inferior margin of the muscularis mucosa (MM/SM1 group: 81 patients), and submucosa invasion > 200 μm below the MM inferior margin (SM2 group: 31 patients). RESULTS: The 5-year overall survival rates in the EP/LPM, MM/SM1, and SM2 groups were 92.6%, 80.0%, and 62.7%, respectively, while the 5-year disease-specific survival rates were 99.7%, 96.9%, and 88.3%, respectively. Multivariate analyses revealed that the invasion depth, Charlson Comorbidity Index (CCI), and prognostic nutritional index (PNI) were independent prognostic factors. Hazard ratios in the MM/SM1 and SM2 groups were 2.25 (95% confidence interval [CI] 1.04-4.83; P = 0.038) and 3.18 (95% CI 1.08-9.34; P = 0.036), respectively, compared to those in the EP/LPM group, while those for patients with a CCI ≥ 3 and PNI ≤ 47.75 were 3.25 (95% CI 1.79-5.89; P < 0.001) and 2.42 (95% CI 1.26-4.65; P = 0.008), respectively. CONCLUSIONS: This study identified that invasion depth, presence of comorbid diseases and preoperative nutritional status are independent prognostic risk factors associated with ESCC patients undergoing ESD.

    DOI: 10.1007/s00464-021-08502-1

    PubMed

  58. 85歳以上の超高齢者に対する早期胃癌内視鏡治療の妥当性についての検討

    山田真也, 土肥統, 春里暁人, 岩井直人, 堀江隆介, 安田剛士, 安田剛士, 山田展久, 堀居雄介, 間嶋淳, 全圭夏, 木村浩之, 八木信明, 内藤裕二, 伊藤義人

    Gastroenterological Endoscopy (Web)   Vol. 63 ( Supplement1 )   2021

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  59. 典型的な経過を示した肝蛭症の一例

    徳田文太, 佐藤修, 春里暁人, 岡野史弥, 山田惠

    日本医学放射線学会秋季臨床大会抄録集   Vol. 57th   2021

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  60. Endoscopic unroofing法が有効であった空腸脂肪腫の1例

    伊谷純一郎, 小林玲央, 井上健, 三宅隼人, 廣瀬亮平, 土井俊文, 土肥統, 春里暁人, 吉田直久, 内山和彦, 石川剛, 高木智久, 保田宏明, 小西英幸, 伊藤義人

    日本消化器病学会近畿支部例会プログラム・抄録集   Vol. 115th   2021

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  61. 残胃癌による輸入脚症候群を発症した一例

    藤田凱斗, 福井勇人, 井上健, 三宅隼人, 廣瀬亮平, 土井俊文, 土肥統, 春里暁人, 吉田直久, 内山和彦, 石川剛, 高木智久, 保田宏明, 小西英幸, 大橋拓馬, 窪田健, 大辻英吾, 伊藤義人

    日本消化器病学会近畿支部例会プログラム・抄録集   Vol. 115th   2021

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  62. 高齢者食道癌薬物療法におけるプラチナ系薬剤選択についての検討

    森田竜一, 石川剛, 石川剛, 朝枝興平, 小林玲央, 宮崎啓, 榊田智喜, 土井俊文, 井上健, 春里暁人, 土肥統, 吉田直久, 内山和彦, 高木智久, 小西博貴, 塩崎敦, 藤原斉, 小西英幸, 内藤裕二, 伊藤義人

    日本高齢消化器病学会誌   Vol. 24 ( 1 )   2021

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  63. 食道ESD長期予後における予後規定因子の探索的研究-多施設共同後向き研究-

    酒井浩明, 岩井直人, 土肥統, 山田真也, 春里暁人, 堀江隆介, 安田剛士, 山田展久, 堀居雄介, 間嶋淳, 全圭夏, 木村浩之, 八木信明, 内藤裕二, 伊藤義人

    Gastroenterological Endoscopy (Web)   Vol. 63 ( Supplement1 )   2021

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  64. 食物アレルギー予防を目指した食品成分による腸内環境制御法の開発

    春里暁人

    ニッポンハム食の未来財団研究助成事業成果報告会要旨集(Web)   Vol. 2020   2021

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  65. A multicenter retrospective study on surveillance endoscopy for detecting gastric cancer in patients after successfully Helicobacter pylori eradication

    安田剛士, 土肥統, 吉田拓馬, 東祐圭, 石田紹敬, 北江博晃, 松村晋矢, 山田真也, 辻俊史, 岩井直人, 寺崎慶, 向井理英子, 堀居雄介, 全圭夏, 間嶋淳, 元好貴之, 春里暁人, 八木信明, 内藤裕二, 伊藤義人

    日本消化管学会雑誌   Vol. 5 ( Supplement )   2021

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  66. 直腸炎型潰瘍性大腸炎の非病変部にIIa+IIc様ポリープ形態を呈した孤発性リンパ濾胞過形成の1例

    岡野史弥, 福居顕文, 高木智久, 高木智久, 竹谷祐栄, 尾松達司, 岡山哲也, 堅田和弘, 井上健, 春里暁人, 土肥統, 沖田美香, 井村徹也, 内藤裕二, 伊藤義人

    日本消化器病学会近畿支部例会プログラム・抄録集   Vol. 115th   2021

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  67. 消化管アレルギーモデルマウスにおけるリコピンの肥満細胞抑制作用

    後田ちひろ, 高木智久, 福家暢夫, 水島かつら, 平井泰子, 東村泰希, 春里暁人, 内山和彦, 伊藤義人, 内藤裕二

    機能性食品と薬理栄養   Vol. 15 ( 3 )   2021

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  68. A Case of Early Gastric Cancer with Eosinophilic Granuloma

    崔哲暢, 堅田和弘, 山内克真, 竹谷祐栄, 福居顕文, 春里暁人, 岡山哲也, 中井理絵, 住吉秀太郎, 原田恭一, 竹本健一, 越野勝博, 當麻敦史, 落合登志哉, 伊藤義人

    京都府立医科大学附属北部医療センター誌   Vol. 113回 ( 1 ) page: 97 - 97   2020.10

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    J-GLOBAL

  69. 難治性肝膿瘍に対する抗菌薬動注療法

    石破 博, 竹内 義人, 岡 浩平, 山内 克真, 福居 顕文, 春里 暁人, 岡山 哲也, 堅田 和弘, 佐藤 修, 伊藤 義人

    京都府立医科大学附属北部医療センター誌   Vol. 6 ( 1 ) page: 40 - 44   2020.3

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    症例は36歳男性。主訴は発熱。肝右葉に多発する内部蜂巣状の膿瘍を認めた。経静脈的抗菌療法により炎症は沈静せず膿瘍は増大した。蜂窩織炎成分主体の病変性状によりドレナージ療法は困難と考え、大腿動脈経由に設置した肝動脈リザーバーを用いて抗菌薬動注療法を開始した。17日目に膿瘍の著明な縮小と炎症反応の鎮静化、28日目に膿瘍は消失した。本例のように従来治療が困難な肝膿瘍に対しては、抗菌薬の肝動注療法が有効である可能性があり、治療法の一つとして考慮する価値がある。(著者抄録)

  70. 肝腫瘍との鑑別が困難であった腸管外間葉腫瘍の一例

    山内 克真, 石破 博, 福居 顕文, 春里 暁人, 岡山 哲也, 堅田 和弘, 竹本 健一, 當麻 敦史, 落合 登志哉, 井村 徹也, 高木 智久, 小西 英幸, 内藤 裕二, 伊藤 義人

    日本消化器病学会近畿支部例会プログラム・抄録集   Vol. 112回   page: 104 - 104   2020.2

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  71. アニサキス症による好酸球性肉芽腫を合併した早期胃癌の一例

    崔哲暢, 山内克真, 竹谷祐栄, 福居顕文, 春里暁人, 岡山哲也, 堅田和弘, 井上健, 土肥統, 高木智久, 小西英幸, 内藤裕二, 竹本健一, 當麻敦史, 落合登志哉, 井村徹也, 伊藤義人

    日本消化器病学会近畿支部例会プログラム・抄録集   Vol. 113th   2020

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  72. 動物ストレスモデルにおけるIBS関連症状と腸内細菌叢の関連性

    鎌田和浩, 安田律, 井上亮, 水島かつら, 福居顕文, 井上健, 春里暁人, 岡山哲也, 堅田和弘, 内山和彦, 石川剛, 高木智久, 内藤裕二, 伊藤義人

    日本消化管学会雑誌   Vol. 4 ( Supplement )   2020

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  73. 高齢C型慢性肝炎患者の治療後の変化

    石破博, 山内克真, 福居顕文, 春里暁人, 岡山哲也, 堅田和弘, 伊藤義人

    日本老年医学会雑誌   Vol. 57 ( 4 )   2020

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  74. 除菌後胃癌に対する画像強調内視鏡観察の優劣性の検討-動画を用いた多施設前向き観察研究-

    松村晋矢, 土肥統, 吉田拓馬, 東祐圭, 北江博晃, 高山峻, 荻田和幸, 水野直樹, 安田剛士, 山田展久, 春里暁人, 堅田和弘, 八木信明, 内藤裕二, 小山田裕一, 伊藤義人

    日本消化管学会雑誌   Vol. 4 ( Supplement )   2020

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  75. 超高齢者の機能評価からみた内視鏡的胃粘膜下層剥離術後偶発症,予後に関する検討

    石田紹敬, 土肥統, 内藤裕二, 伊藤義人, 山田真也, 岩井直人, 堀居雄介, 間嶋淳, 堀江隆介, 山田展久, 春里暁人, 全圭夏, 八木信明

    Gastroenterological Endoscopy (Web)   Vol. 62 ( Supplement2 )   2020

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  76. 超高齢者における内視鏡的胃粘膜下層剥離術の安全性に関する検討-多施設共同研究-

    石田紹敬, 土肥統, 内藤裕二, 山田真也, 安田剛士, 岩井直人, 陶山遥介, 堀居雄介, 間嶋淳, 堀江隆介, 堀江隆介, 山田展久, 春里暁人, 全圭夏, 八木信明, 伊藤義人, 伊藤義人

    Gastroenterological Endoscopy (Web)   Vol. 62 ( Supplement1 )   2020

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  77. アレルギー アナフィラキシー、気道炎症/喘息およびその他(皮膚炎を除く) 食品乳化剤polysorbate-80は結腸Th2サイトカインの発現増加により実験的食物アレルギーを増悪化する(Allergy-2: Anaphylaxis, airway inflammation/asthma and others (except dermtitis) Dietary Emulsifier Polysorbate-80 Exacerbates Experimental Food Allergy with Increased Expressions of Colonic Th2 Cytokines)

    Harusato Akihito, Chassaing Benoit

    日本免疫学会総会・学術集会記録   Vol. 48 ( Proceedings ) page: 3 - P   2019.11

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  78. 腸内細菌と消化器疾患-研究の進歩と治療への応用- 出生後早期の腸内細菌叢が大腸発癌に及ぼす影響に関する検討

    春里 暁人, 内藤 裕二, 伊藤 義人

    日本消化器病学会雑誌   Vol. 116 ( 臨増大会 ) page: A678 - A678   2019.11

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  79. 抗TNF-α抗体製剤無効の潰瘍性大腸炎に合併した難治性結節性紅斑及び脊椎関節炎にトファシチニブが奏功した一例

    中川 知恵, 春里 暁人, 高木 智久, 山内 克真, 石破 博, 福居 顕文, 岡山 哲也, 堅田 和弘, 内山 和彦, 保田 宏明, 阪上 順一, 小西 英幸, 内藤 裕二, 伊藤 義人

    日本消化器病学会近畿支部例会プログラム・抄録集   Vol. 111回   page: 79 - 79   2019.10

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  80. cold polypectomyの現状と課題 生理食塩水局注併用コールドスネアポリペクトミーの有用性に関する二施設共同前向きランダム化比較試験

    春里 暁人, 稲田 裕, 井村 徹也, 中川 知恵, 岡 浩平, 岩井 直人, 石破 博, 原 祐, 辻 俊史, 福居 顕文, 岡山 哲也, 奥田 隆史, 堅田 和弘, 永田 昭博, 香川 惠造, 高木 智久, 内藤 裕二, 伊藤 義人

    日本大腸肛門病学会雑誌   Vol. 72 ( 9 ) page: A61 - A61   2019.9

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  81. 肝硬変患者の肝性腹水・浮腫に対するTolvaptanの治療反応性の検討

    石破 博, 岡 浩平, 福居 顕文, 春里 暁人, 岡山 哲也, 堅田 和弘, 伊藤 義人

    京都府立医科大学附属北部医療センター誌   Vol. 5 ( 1 ) page: 17 - 23   2019.3

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    Tolvaptanは肝性腹水の治療に非常に有用な薬剤だが、日常臨床ではしばしば無効例を経験する。本研究ではTolvaptanへの反応性について、治療前後の腹水、肝予備能、血液生化学的検査の変化を検討したところ、Tolvaptanへの反応性は、腎機能、肝予備能に規定されることがわかった。またTolvaptan無効例でもアルブミン補充や腹水濾過再静注(CART)を併用することで、治療効果の改善を認めた。本研究は少数例の検討であり、今後症例の集積が必要である。(著者抄録)

  82. 胆道再建術後に吐血で発症した多血性下部胆管癌の一例

    張 里宇, 春里 暁人, 岡 浩平, 石破 博, 福居 顕文, 岡山 哲也, 堅田 和弘, 當麻 敦史, 落合 登志哉, 高木 智久, 内藤 裕二, 伊藤 義人

    日本消化器病学会近畿支部例会プログラム・抄録集   Vol. 110回   page: 93 - 93   2019.2

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  83. 内視鏡下に採取した検体を用いた機能性ディスペプシア患者の粘膜関連細菌叢の検討

    福居顕文, 福居顕文, 高木智久, 内藤裕二, 柏木里織, 稲田裕, 稲田裕, 春里暁人, 春里暁人, 土肥統, 岡山哲也, 岡山哲也, 堅田和弘, 堅田和弘, 鎌田和浩, 内山和彦, 石川剛, 半田修, 半田修, 伊藤義人, 石破博, 石破博

    Gastroenterological Endoscopy (Web)   Vol. 61 ( Supplement1 )   2019

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  84. 内視鏡下採取検体を用いた機能性ディスペプシア患者と健常人との粘膜内細菌叢の比較検討

    福居顕文, 福居顕文, 高木智久, 岡浩平, 石破博, 石破博, 稲田裕, 稲田裕, 春里暁人, 春里暁人, 岡山哲也, 岡山哲也, 堅田和弘, 堅田和弘, 柏木里織, 半田修, 半田修, 内藤裕二

    日本消化管学会雑誌   Vol. 3 ( Supplement )   2019

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  85. Dietary Emulsifier Polysorbate-80 Exacerbates Experimental Food Allergy with Increased Expressions of Colonic Th2 Cytokines

    HARUSATO Akihito, CHASSAING Benoit

    日本免疫学会総会・学術集会記録(CD-ROM)   Vol. 48   2019

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  86. 生理食塩水局注併用コールドスネアポリペクトミーの有用性に関する二施設共同前向きランダム化比較試験

    春里暁人, 稲田裕, 井村徹也, 中川知恵, 岡浩平, 岩井直人, 石破博, 原祐, 辻俊史, 福居顕文, 岡山哲也, 奥田隆史, 堅田和弘, 永田昭博, 香川惠造, 高木智久, 高木智久, 内藤裕二, 伊藤義人

    日本大腸肛門病学会雑誌(Web)   Vol. 72 ( 9 )   2019

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  87. 早期胃癌非治癒切除例における患者背景を考慮した予後規定因子の探索

    岩井直人, 岩井直人, 土肥統, 春里暁人, 伊藤義人

    日本消化器病学会近畿支部例会プログラム・抄録集   Vol. 111th   2019

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  88. 超高齢発症stageIA胃癌患者の予後予測因子についての検討

    山田真也, 土肥統, 春里暁人, 堀江隆介, 安田剛士, 間嶋淳, 堀居雄介, 鎌田和浩, 八木信明, 内藤裕二, 吉田憲正, 伊藤義人

    Gastroenterological Endoscopy (Web)   Vol. 60 ( Supplement2 )   2018

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  89. 非ステロイド性抗炎症薬惹起性小腸潰瘍に対するアガロオリゴ糖の予防効果

    東村 泰希, 内藤 裕二, 高木 智久, 谷村 祐子, 水島 かつら, 春里 暁人, 福居 顕文, 寄木 浩行, 半田 修, 大野木 宏, 吉川 敏一

    ビタミン   Vol. 89 ( 2 ) page: 53 - 55   2015.2

  90. Adoptive Transfer of Heme Oxygenase-1 Highly Expressed Macrophage Ameliorated TNBS-Induced Colitis in Mice Reviewed

    Akihito Harusato, Yuji Naito, Tomohisa Takagi, Kazuhiko Uchiyama, Katsura Mizushima, Yasuko Hirai, Toshifumi Tsuji, Wataru Fukuda, Hiroyuki Yoriki, Munehiro Kugai, Ryusuke Horie, Akifumi Fukui, Takaya Iida, Kazuhiro Katada, Osamu Handa, Hiroshi Ichikawa, Akihiko Muto, Kazuhiko Igarashi, Toshikazu Yoshikawa

    GASTROENTEROLOGY   Vol. 142 ( 5 ) page: S883 - S883   2012.5

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    Web of Science

  91. Attenuation of Ischemia/Reperfusion-Challenged Intestinal Inflammation in BTB and CNC Homolog 1 (BACH1) Deficient Mice Reviewed

    Kazuhiro Katada, Tomohisa Takagi, Hiroyuki Yoriki, Akihito Harusato, Kazuhiko Uchiyama, Osamu Handa, Takeshi Ishikawa, Nobuaki Yagi, Satoshi Kokura, Hiroshi Ichikawa, Yuji Naito, Toshikazu Yoshikawa

    GASTROENTEROLOGY   Vol. 140 ( 5 ) page: S698 - S699   2011.5

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    Web of Science

  92. The Therapeutic Effect of Heme Oxygenase-1 in the Indomethacin-Induced Intestinal Injury in Mice Reviewed

    Hiroyuki Yoriki, Yuji Naito, Tomohisa Takagi, Akihito Harusato, Shinya Yamada, Toshifumi Tsuji, Munehiro Kugai, Ryusuke Horie, Ken Inoue, Kohei Fukumoto, Naohisa Yoshida, Kazuhiko Uchiyama, Osamu Handa, Nobuaki Yagi, Satoshi Kokura, Yukiko Minamiyama, Hiroshi Ichikawa, Toshikazu Yoshikawa

    GASTROENTEROLOGY   Vol. 140 ( 5 ) page: S653 - S653   2011.5

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    Web of Science

  93. Role of the Metallothionine in the Murine Experimental Colitis Reviewed

    Toshifumi Tsuji, Yuji Naito, Tomohisa Takagi, Hiroyuki Yoriki, Shinya Yamada, Akihito Harusato, Katsura Mizushima, Yasuko Hirai, Kazuhiro Katada, Kuzuhiko Uchiyama, Osamu Handa, Hideyuki Konishi, Nobuaki Yagi, Naoki Wakabayashi, Hiroshi Ichikawa, Junko Suzuki, Rie Yanagisawa, Hirohisa Takano, Masahiko Satoh, Toshikazu Yoshikawa

    GASTROENTEROLOGY   Vol. 140 ( 5 ) page: S518 - S518   2011.5

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    Web of Science

  94. Rikkunshito, a Japanese Traditional Herbal Medicine, Promotes Murine Gastric Ulcer Healing Through the Inhibition of the Oxidative Modification to Proteins Reviewed

    Ryusuke Horie, Yuji Naito, Tomohisa Takagi, Katsura Mizushima, Toshifumi Tsuji, Munehiro Kugai, Hiroyuki Yoriki, Shinya Yamada, Kohei Fukumoto, Ken Inoue, Akihito Harusato, Kazuhiko Uchiyama, Osamu Handa, Satoshi Kokura, Hiroshi Ichikawa, Toshikazu Yoshikawa

    GASTROENTEROLOGY   Vol. 140 ( 5 ) page: S315 - S316   2011.5

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    Web of Science

  95. Pirfenidone Regulates Intestinal Fibrosis Through the Inhibition of HSP47 Expression in a Rat Colitis Model Reviewed

    Ken Inoue, Yuji Naito, Tomohisa Takagi, Natsuko Hayashi, Yasuko Hirai, Katsura Mizushima, Toshifumi Tsuji, Hiroyuki Yoriki, Munehiro Kugai, Ryusuke Horie, Kohei Fukumuto, Shinya Yamada, Akihito Harusato, Naohisa Yoshida, Kazuhiko Uchiyama, Takeshi Ishikawa, Osamu Handa, Hideyuki Konishi, Naoki Wakabayashi, Nobuaki Yagi, Hiroshi Ichikawa, Satoshi Kokura, Toshikazu Yoshikawa

    GASTROENTEROLOGY   Vol. 140 ( 5 ) page: S770 - S770   2011.5

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    Web of Science

  96. Deficiency of BACHI Ameliorates TNBS-Induced Colitis in Mice Thorough the Anti-Inflammatory Function of HO-I Highly Expressed Macrophages Reviewed

    Akihito Harusato, Yuji Naito, Tomohisa Takagi, Kazuhiko Uchiyama, Katsura Mizushima, Yasuko Hirai, Toshifumi Tsuji, Hiroyuki Yoriki, Munehiro Kugai, Ryusuke Horie, Ken Inoue, Kohei Fukumoto, Shinya Yamada, Osamu Handa, Satoshi Kokura, Hiroshi Ichikawa, Akihiko Muto, Kazuhiko Igarashi, Toshikazu Yoshikawa

    GASTROENTEROLOGY   Vol. 140 ( 5 ) page: S649 - S649   2011.5

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    Web of Science

  97. Decreased Expression of Peroxiredoxin-6 in Murine Dextran Sodium Sulfate-Induced Colitis Identified By 2-Dimensional Fluorescence Difference in Gel Electrophoresis Reviewed

    Tatsushi Omatsu, Yuji Naito, Tomohisa Takagi, Katsura Mizushima, Hitomi Okada, Kohei Fukumoto, Akihito Harusato, Ikuhiro Hirata, Yoko Hamano, Tomoko Oya-Ito, Osamu Handa, Nobuaki Yagi, Satoshi Kokura, Hiroshi Ichikawa, Hideshi Fujiwake, Toshikazu Yoshikawa

    GASTROENTEROLOGY   Vol. 136 ( 5 ) page: A247 - A247   2009.5

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  98. Successful portal-systemic shunt occlusion with balloon-occluded retrograde transvenous obliteration for portosystemic encephalopathy without liver cirrhosis. International journal

    Osamu Tanaka, Kiyoshi Ishihara, Hirokazu Oyamada, Akihito Harusato, Taiji Yamaguchi, Masaru Ozawa, Koji Nakano, Takuji Yamagami, Tsunehiko Nishimura

    Journal of vascular and interventional radiology : JVIR   Vol. 17 ( 12 ) page: 1951 - 5   2006.12

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    Language:English  

    A 68-year-old woman was admitted to the authors' hospital for hepatic encephalopathy. Her laboratory data and computed tomography findings were not suggestive of liver cirrhosis. Superior mesenteric angiography revealed an extrahepatic portal-systemic shunt with a main cause of hepatic encephalopathy. Despite treatment with branched-chain amino acid, lactulose, and kanamycin, hyperammonemia was prolonged, and the portal-systemic shunt was therefore treated with balloon-occluded retrograde transvenous obliteration. After the procedure, hyperammonemia was improved, and there were no signs of recurrent portal-systemic encephalopathy.

    PubMed

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Presentations 1

  1. IL-36 Signaling Controls the Induced Regulatory T Cell – TH9 Cell Balance and Gut Inflammation. Lloyd Mayer, MD, Young IBD Investigators Workshop, Advances in Inflammatory Bowel Diseases, 2016 Dec 8, Orlando. Invited

    2016 

KAKENHI (Grants-in-Aid for Scientific Research) 4

  1. Intestinal homeostasis and the mechanism of food allergy

    Grant number:22K11731  2022.4 - 2025.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Authorship:Principal investigator 

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

  2. Antigen presenting cell mediated regulation of intestinal inflammation

    Grant number:18K15128  2018.4 - 2021.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists  Grant-in-Aid for Early-Career Scientists

  3. IL-36 mediated regulation of intestinal inflammation

    Grant number:17H07013  2017.8 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity Start-up  Grant-in-Aid for Research Activity Start-up

  4. IL-36 mediated regulation of acute and chronic intestinal inflammation

    2016.1 - 2018.12

    Crohn`s and Colitis Foundation of America  Research Fellowship Award 

    Akihito Harusato

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    Authorship:Principal investigator 

 

Teaching Experience (Off-campus) 4

  1. Gastroenterology

    2021.4 - 2024.4 Kyoto Prefectural University of Medicine)

  2. Pathology

    2019.4 - 2021.3 Kyoto Prefectural School of Nursing)

  3. Gastroenterology

    2006.4 - 2007.3 Asahi University)

  4. Physiology

    2005.4 - 2006.3 National Hospital Organization, Maizuru Medical Center)

 

Social Contribution 2

  1. 大学国際保健ボランティア

    2024.5

  2. 生命のがん教育

    Role(s):Lecturer

    京都府  2021.4 - 2024.4