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HOSHI NamikoGraduate School of Medicine / Faculty of Medical SciencesAssociate Professor
Researcher basic information
■ Research Areas■ Committee History
- Dec. 2024 - Present, アジア炎症性腸疾患学会総会, Comittee member for the 13th Annual Meeting of AOCC
- Nov. 2024 - Present, 日本消化器病学会, 炎症性腸疾患(IBD)ガイドライン作成委員
- 2023 - Present, 日本炎症性腸疾患学会学術集会, プログラム委員
- 2023 - Present, 日本医学会連合による領域横断的連携活動事業 多学会連携による慢性疾患患者の挙児希望を叶えるための横断的指針作成, ワーキンググループ委員
- Apr. 2019 - Present, 難治性炎症性腸管障害に関する調査研究, 研究協力者
- 2017 - Present, 日本炎症性腸疾患学会, 国際交流委員
- - Present, 日本炎症性腸疾患学会, 代議員
- 日本炎症性腸疾患学会, 研究助成委員
- 日本消化器病学会, 評議員
Research activity information
■ Award- 2023 日本消化器病学会, 日本消化器病学会女性研究者賞
- Nov. 2013 The American Gastroenterological Association, The JUCC Award of the 7th JUCC, Cell type-specific role of MyD88 in commensal-dependent colitisInternational society
- Elsevier BV, Feb. 2025, Biochemical and Biophysical Research Communications, 151446 - 151446Scientific journal
- BACKGROUND: A serum biomarker for diagnosing ulcerative colitis (UC) remains to be established. Although we recently reported an anti-integrin αvβ6 antibody (V6 Ab) for diagnosing UC with high sensitivity and specificity, no large-scale validation study exists. This study aimed to validate the diagnostic value of V6 Ab for UC using a nationwide multicenter cohort study. METHODS: We measured V6 Ab titers in patients definitively diagnosed with UC, Crohn's disease (CD), or other gastrointestinal disorders (OGDs). The primary outcome was the diagnostic value of V6 Ab. Secondary outcomes were factors associated with false-negative results in patients with UC and false-positive results in patients without UC and the heterogeneity of the diagnostic value of V6 Ab among the participating facilities. RESULTS: We enrolled 1241, 796, and 206 patients with UC, CD, and OGD, respectively, from 28 Japanese high-volume referral centers. The diagnostic sensitivity of V6 Ab for UC was 87.7%, and its specificities for CD and OGDs were 82.0% and 87.4%, respectively. Multivariable logistic regression analysis showed that false-negative results were associated with older age at the time of sample collection, current smokers, lower partial Mayo score, and not receiving advanced therapies in patients with UC, and false-positive results were associated with colonic CD in patients with CD. No factor was associated with false-positive results in patients with OGDs. There were no significant differences in the diagnostic value of V6 Ab among the centers. CONCLUSIONS: The diagnostic value of V6 Ab for UC was validated in the large-scale nationwide multicenter study.Nov. 2024, Journal of gastroenterology, English, Domestic magazineScientific journal
- BACKGROUND: Proanthocyanidins (PACs) from black soybean seed coat have antioxidant and anti-tumorigenic properties. We investigated the anti-tumor properties and mechanisms of action of PACs on colorectal cancer (CRC). METHODS: We fed the APCmin/+ mice, which are highly susceptible to spontaneous intestinal adenoma formation, diets supplemented with or without PACs for 7 weeks and assessed adverse effects, the number and size of intestinal polyps, and the expression of pro- and anti-proliferative proteins in the intestine. The mouse gut microbiome composition was analyzed, and the concentrations of gut short-chain fatty acids (SCFAs) were quantified. We also compared CRC incidence in Tamba in Japan, where black soybean is consumed frequently, with that in the rest of Japan. RESULTS: The number and size of intestinal polyps notably decreased in the PAC-fed mice. Compared with control mice, the PAC-fed mice showed lower expression of proliferation markers proliferating cell nuclear antigen and β catenin and a higher expression of the anti-inflammatory protein oligomeric mucus gel-forming. PAC supplementation increased the prevalence and concentrations of beneficial gut microbes and SCFAs, respectively. CONCLUSIONS: Diet supplemented with black soybean-derived PACs could prevent CRC development in mice through gut microbiome remodeling. Regions consuming black soybeans have low CRC incidence. Notably, the incidence of CRC, breast cancer, and liver cancer was significantly lower in Tamba than in the rest of Hyogo Prefecture or Japan. Future studies should delineate the mechanisms underlying the CRC-protective effects of PACs. Nevertheless, our results demonstrate the potential of including PACs in dietary recommendations for cancer prevention.Nov. 2024, Cancers, 16(22) (22), English, International magazineScientific journal
- (公社)日本小児科学会, Apr. 2024, 日本小児科学会雑誌, 128(4) (4), 624 - 624, Japanese潰瘍性大腸炎の発症時に免疫性血小板減少症を合併した1例
- Not all patients with ulcerative colitis (UC) respond initially to treatment with biologic agents, and predicting their efficacy prior to treatment is difficult. Vedolizumab, a humanized monoclonal antibody against alpha 4 beta 7 (α4β7) integrin, suppresses immune cell migration by blocking the interaction between α4β7 integrin and mucosal addressin cell adhesion molecule 1. Reports about histological features that predict vedolizumab efficacy are scarce. So, we examined the association between histological features and vedolizumab efficacy. This was a multicenter, retrospective study of patients with UC treated with vedolizumab. Biopsy specimens taken from the colonic mucosa prior to vedolizumab induction were used, and the areas positively stained for CD4, CD68, and CD45 were calculated. Clinical and histological features were compared between those with and without remission at week 22, and the factors associated with clinical outcomes were identified. We enrolled 42 patients. Patients with a high CD4+ infiltration showed a better response to vedolizumab [odds ratio (OR) = 1.44, P = 0.014]. The concomitant use of corticosteroids and high Mayo scores had a negative association with the vedolizumab response (OR = 0.11, P = 0.008 and OR = 0.50, P = 0.009, respectively). Histological evaluation for CD4+ cell infiltration may be helpful in selecting patients who can benefit from vedolizumab.Nov. 2023, Scientific reports, 13(1) (1), 20262 - 20262, English, International magazineScientific journal
- BACKGROUND/PURPOSE OF THIS STUDY: It has been recommended that individuals with inflammatory bowel disease (IBD) be vaccinated against Coronavirus disease - 19 (COVID-19). Recently, we documented the incidence of side effects (SEs) after COVID-19 immunization among individuals with IBD in Japan. However, the study did not show differences between the types of IBD or the patients' clinical backgrounds. In this survey, we aimed at investigating whether the frequency of SEs differed among patients with IBD. METHODS: A cross-sectional survey was conducted among adult patients with IBD at Kobe University between March 2022 and September 2022. RESULTS: Total 195 patients, including 134 with ulcerative colitis (UC) and 61 with Crohn's disease (CD), completed the questionnaire and were included in the analysis. Of these, 92.3%, 91.3% and 44.1% received the initial, second and third dose of the COVID-19 vaccine, respectively. The frequency of local symptoms following the initial, second and third dose of the vaccine was comparable between patients with UC and CD (69.6% vs. 72.7%, 64.2% vs. 69.1% and 63.5% vs. 73.9%, respectively). Muscle pain after the initial and second doses of the COVID-19 vaccine was more common among patients treated with corticosteroids (58.1% vs. 37.6% and 60.0% vs. 31.8%, p < 0.05). Female sex, younger age and current or former smoking were associated with an increased incidence of fever or chills after the initial dose of the vaccine (p < 0.05). In contrast, corticosteroid use was identified as a factor associated with an increased incidence of muscle pain after the initial dose of vaccine (p < 0.05). CONCLUSION: The use of corticosteroids could increase the risk of muscle pain following COVID-19 vaccination. Additionally, factors such as female sex, younger age and current or former smoking can affect the incidence of fever or chills. This information should encourage patients with IBD to get vaccinated against COVID-19.Oct. 2023, Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology, 42(5) (5), 701 - 707, English, International magazineScientific journal
- Mycobacterium avium complex (MAC) is an important cause of opportunistic infections in immunosuppressed hosts, such as patients with HIV infection and solid organ transplant recipients. MAC disease usually presents in 4 distinct clinical categories: chronic pulmonary disease, disseminated disease, skin/soft-tissue infection, and superficial lymphadenitis. However, clinical reports on gastrointestinal (GI) MAC disease are rare, especially in patients without HIV infection or a history of organ transplantation. We describe a case of non-HIV-associated GI MAC disease in a patient with long-term mycophenolate mofetil use. In this case, MAC organisms in the GI tract and ascites were observed. Endoscopy revealed a unique colonic image with large, deep epithelial denudations. This suggests that apart from patients with HIV infection or transplant recipients, those treated with immunosuppressants can have disseminated MAC. Therefore, internal physicians need to monitor patients undergoing mycophenolate mofetil immunosuppressant therapy.Apr. 2023, ACG case reports journal, 10(4) (4), e01033, English, International magazine
- (一社)日本小児栄養消化器肝臓学会, Apr. 2023, 日本小児栄養消化器肝臓学会雑誌, 37(1) (1), 35 - 35, Japanese
- (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 625 - 626, Japanese一過性の細胞免疫不全所見を認めた超早期発症型炎症性腸疾患の1例
- Abstract Background Amino acid transporters play an important role in supplying nutrition to cells and are associated with cell proliferation. L-type amino acid transporter 1 (LAT1) is highly expressed in many types of cancers and promotes tumor growth; however, how LAT1 affects tumor development is not fully understood. Methods To investigate the role of LAT1 in intestinal tumorigenesis, mice carrying LAT1 floxed alleles that also expressed Cre recombinase from the promoter of gene encoding Villin were crossed to an ApcMin/+ background (LAT1fl/fl; vil-cre; ApcMin/+), which were subject to analysis; organoids derived from those mice were also analyzed. Results This study showed that LAT1 was constitutively expressed in normal crypt base cells, and its conditional deletion in the intestinal epithelium resulted in fewer Paneth cells. LAT1 deletion reduced tumor size and number in the small intestine of ApcMin/+ mice. Organoids derived from LAT1-deleted ApcMin/+ intestinal crypts displayed fewer spherical organoids with reduced Wnt/β-catenin target gene expression, suggesting a low tumor-initiation capacity. Wnt3 expression was decreased in the absence of LAT1 in the intestinal epithelium, suggesting that loss of Paneth cells due to LAT1 deficiency reduced the risk of tumor initiation by decreasing Wnt3 production. Conclusions LAT1 affects intestinal tumor development in a cell-extrinsic manner through reduced Wnt3 expression in Paneth cells. Our findings may partly explain how nutrient availability can affect the risk of tumor development in the intestines.Springer Science and Business Media LLC, Feb. 2023, Journal of GastroenterologyScientific journal
- BACKGROUND: Patients with inflammatory bowel disease (IBD) are recommended to receive the coronavirus disease 2019 (COVID-19) vaccine. However, a recent survey showed that patients with IBD are more hesitant to receive the vaccine than the general population. Detailed information on the side effects of the COVID-19 vaccine is necessary to encourage vaccination among patients with IBD. AIM: To investigate the frequency of side effects following COVID-19 vaccination in patients with IBD in Japan. STUDY DESIGN: a cross-sectional survey was conducted using a questionnaire administered to adult patients with IBD in a tertiary medical facility. RESULTS: Among the participants who answered the questionnaire, 92.6%, 91.5%, and 41.5% of the participants had received their first, second, and third doses of the COVID-19 vaccine, respectively. Of the vaccinated participants, 88.3%, 86.3%, and 89.0% experienced side effects after receiving the first, second, and third doses of the vaccine, respectively. The incidences of fever, chills, and headaches were significantly higher among female participants than among male participants (p < 0.05). However, the frequencies of most side effects were comparable between the BNT162b2 mRNA and mRNA-1273 vaccines. CONCLUSION: The findings of our survey can help encourage patients with IBD to receive the COVID-19 vaccine.Sep. 2022, Digestive diseases and sciences, English, International magazineScientific journal
- Resistant starch (RS) has been reported to improve steatosis as well as obesity. Type 4 resistant starch (RS4), a chemically modified starch, is particularly hard to digest and suggesting higher efficacy. However, because the effects of RS4 on steatosis are not yet fully understood, the effects of RS4 on steatosis were examined using a murine high-fat diet model. Seven-week-old male mice were divided into three groups and fed a normal diet, a high-fat diet (HFD), or a high-fat diet with added RS (HFD + RS). Amylofiber SH® produced from acid-treated corn starch was used as the dietary RS. At 22 weeks old, hepatic steatosis and short chain fatty acid (SCFA) content and gut microbiota in cecum stool samples were analyzed. The ratio of body weight to 7 weeks was significantly suppressed in the HFD + RS group compared to the HFD group (132.2 ± 1.4% vs. 167.2 ± 3.9%, p = 0.0076). Macroscopic and microscopic steatosis was also suppressed in the HFD + RS group. Analysis of cecum stool samples revealed elevated SCFA levels in the HFD + RS group compared with the HFD group. Metagenome analysis revealed that Bifidobacterium (17.9 ± 1.9% vs. 3.6 ± 0.7%, p = 0.0019) and Lactobacillus (14.8 ± 3.4% vs. 0.72 ± 0.23%, p = 0.0045), which degrade RS to SCFA, were more prevalent in the HFD + RS group than the HFD group. In conclusion, RS4 suppressed steatosis, and increased Bifidobacterium and Lactobacillus, and SCFAs. RS4 may prevent steatosis by modulating the intestinal environment.May 2022, Journal of food science, 87(5) (5), 2173 - 2184, English, International magazineScientific journal
- BACKGROUND: Behçet's disease (BD) is a recurrent multisystem inflammatory disease. Anti-tumor necrosis factor (TNF) α agents have been used to treat patients with intestinal BD with severe disease activity or those who are resistant to conventional treatments; however, the long-term efficacy of anti-TNFα agents in intestinal BD remains unclear. In the present study, we investigated the clinical outcomes and predictors of discontinuation of anti-TNFα agents in patients with intestinal BD. METHODS: We reviewed the medical records of patients with intestinal BD who received first-line anti-TNFα agents between January 2009 and June 2020. The primary outcome was the percentage of patients who continued anti-TNFα therapy for 48 weeks. Secondary outcomes included the percentage of patients who achieved marked improvement, complete remission, and mucosal healing, as well as predictors of discontinuation of anti-TNFα agents. RESULTS: A total of 29 patients were included in the study. Twenty-two (75.9%) patients continued anti-TNFα therapy for 48 weeks. The percentage of patients who achieved marked improvement, complete remission, and mucosal healing at week 48 was 48.3%, 37.9%, and 48.3%, respectively. At week 96, 11 (37.9%) patients achieved marked improvement, complete remission, and mucosal healing. A higher C-reactive protein level (CRP; ≥ 1 mg/dL) at baseline was a predictor of discontinuation of anti-TNFα agents. CONCLUSIONS: The 48-week continuation rate of anti-TNFα agents was 75.9% in bio-naïve patients with intestinal BD. However, a higher baseline CRP level (≥ 1 mg/dL) was associated with discontinuation of anti-TNFα agents.Mar. 2022, BMC gastroenterology, 22(1) (1), 149 - 149, English, International magazineScientific journal
- The human gut harbors a complex microbial community that performs a range of metabolic, physiological, and immunological functions. The host and its inhabiting microorganisms are often referred to as a "superorganism." Dysbiosis of gut microflora has been associated with the pathogenesis of intestinal disorders including inflammatory bowel disease, colorectal cancer, and extra-intestinal disorders such as cardiovascular disease. Therefore, gut microbiome interventions are important for the prevention and treatment of diseases. However, ethical, economic, scientific, and time constraints limit the outcome of human intervention or animal studies targeting gut microbiota. We recently developed an in vitro batch fermentation model (the Kobe University Human Intestinal Microbiota Model, KUHIMM) that is capable of hosting a majority of gut microbial species in humans and also detects the metabolites produced by microorganisms in real time. In this mini review, we elucidated the characteristics of the KUHIMM and its applicability in analyzing the effect of diet, drugs, probiotics, and prebiotics on intestinal bacteria. In addition, we introduce as examples its application to disease models, such as ulcerative colitis, in which intestinal bacteria are intricately involved in the process of pathogenesis. We also discuss the potential of the KUHIMM in precision medicine. KEY POINTS: • In vitro gut fermentation model to simulate human colonic microbiota • Screening of potential prebiotics and probiotic candidates in healthy model • Construction of disease models of ulcerative colitis and coronary artery disease.Lead, Apr. 2021, Applied microbiology and biotechnology, 105(7) (7), 2625 - 2632, English, International magazine[Refereed][Invited]Scientific journal
- Research Square, Mar. 2021
Abstract W27 monoclonal immunoglobulin A (IgA) suppresses pathogenicEscherichia coli cell growth; however its effect on the human intestine remains unclear. We thus aimed to determine how W27 IgA affects the human colonic microbiota using thein vitro microbiota model. This model was established using fecal samples collected from 12 healthy volunteers; after anaerobic cultivation, each model was found to retain the genera found in the original human fecal samples. After pre-incubating W27 IgA with the respective fecal sample in aerobic condition, the mixture of W27 IgA (final concentration, 0.5 µg/mL) and each fecal sample was added to thein vitro microbiota model and cultured under anaerobic condition,. Next-generation sequencing of the bacterial 16S rRNA gene revealed that W27 IgA addition significantly decreased the relative abundance of bacteria related to the genusEscherichia in the model. Additionally, at a final concentration of 5 µg/mL, W27 IgA delayed growth in pure culture ofEscherichia coli isolated from human fecal samples. Our study thus revealed the suppressive effect of W27 IgA on the genusEscherichia at relatively low-concentrations and the usefulness of anin vitro microbiota model to evaluate the effect of IgA as a gut microbiota regulator. - Autoimmune enteropathy (AIE) is a rare disease, characterized by intractable diarrhea, villous atrophy of the small intestine, and the presence of circulating anti-enterocyte autoantibodies. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, and mutations in FOXP3, which is a master gene of regulatory T cells (Tregs), are major causes of AIE. Recent studies have demonstrated that mutations in other Treg-associated genes, such as CD25 and CTLA4, show an IPEX-like phenotype. We present the case of a 13-year-old girl with CTLA4 haploinsufficiency, suffering from recurrent immune thrombocytopenic purpura and intractable diarrhea. We detected an autoantibody to the AIE-related 75 kDa antigen (AIE-75), a hallmark of the IPEX syndrome, in her serum. She responded well to a medium dose of prednisolone and a controlled dose of 6-mercaptopurine (6-MP), even after the cessation of prednisolone administration. Serum levels of the soluble interleukin-2 receptor and immunoglobulin G (IgG) were useful in monitoring disease activity during 6-MP therapy. In conclusion, autoimmune-mediated mechanisms, similar to the IPEX syndrome, may be involved in the development of enteropathy in CTLA4 haploinsufficiency. Treatment with 6-MP and monitoring of disease activity using serum levels of soluble interleukin-2 receptor and IgG is suggested for such cases.Corresponding, Jan. 2021, Intestinal research, 20(1) (1), 144 - 149, English, International magazine[Refereed]
- Effect of Daikenchuto On Spontaneous Intestinal Tumors in ApcMin/+ Mice.Daikenchuto (TU-100) is herbal medicine which predominantly contains ginger, Japanese pepper, and ginseng. We investigated whether TU-100 can affect the composition of gut flora and intestinal tumor development using ApcMin/+ mice, a murine model of intestinal tumor. Bacterial 16S rRNA sequencing and short-chain fatty acid analysis were performed on faecal samples. Tumor number and size were analysed. Any change in gene expression of the tumor tissues was assessed by real-time PCR. Principal coordinate analysis (PCoA) showed that the faecal microbiota cluster of TU-100-fed mice was different from the microbiota of control mice. However, no significant difference was observed in the concentration of short-chain fatty acids, tumor number, and gene expression levels between the two groups. Our data showed that TU-100 can affect the intestinal environment; however, it does not contribute in tumor progression or inhibition in our setting.Corresponding, Jan. 2021, The Kobe journal of medical sciences, 66(4) (4), E139-E148, English, Domestic magazine[Refereed]Scientific journal
- S. Karger AG, 2021, Medical Principles and Practice, EnglishScientific journal
- Adrenic acid (ADA), which is an endogenously synthesized polyunsaturated free fatty acid, was significantly increased in nonalcoholic fatty liver disease (NAFLD) patients and NAFLD-model mice compared with the corresponding controls in our previous study. To elucidate the involvement of ADA in NAFLD and nonalcoholic steatohepatitis (NASH), we examined ADA-induced lipotoxicity in human hepatocarcinoma HepG2 cells. The ROS production in HepG2 cells was increased by exposure to ADA. It was also shown that the treatment with ADA decreased cell viability in a dose-dependent manner. The N-Acetyl-L-Cysteine pretreatment counteracted this ADA-induced ROS production and cell death. Furthermore, ADA modulated the expressions of SOD2, HO-1 and Gpx1 as antioxidant enzymes. These findings suggest that ADA could induce oxidative stress accompanied by cell death, providing new insights into lipotoxicity that is involved in the pathogenesis of NAFLD and NASH.Nov. 2020, Biochemical and biophysical research communications, 532(4) (4), 620 - 625, English, International magazineScientific journal
- The aim of this study was to clarify the effect of the spore-forming and lactic acid-producing probiotic strain, Bacillus coagulans SANK 70258, on human colonic microbiota of healthy subjects and ulcerative colitis patients. A model culture system was employed to construct the in vitro human colonic microbiota, to retain the bacterial species richness and simulate the patient's disordered composition, from the fecal inoculum. Bacterial 16S rRNA gene sequencing confirmed that administration of B. coagulans SANK 70258 (at an initial concentration of 4 × 107-total cells/mL) suppressed bacteria related to the family Enterobacteriaceae in the microbiota models for both healthy subjects (P = 0.016) and ulcerative colitis patients (P = 0.023). In addition, administration of B. coagulans SANK 70258 increased bacteria related to the family Lachnospiraceae (P = 0.031), thereby enhancing butyrate production (P = 0.031) in the microbiota models of healthy subjects. However, these changes were not observed in the microbiota models of ulcerative colitis patients, likely owing to the low abundance of Lachnospiraceae species. This study demonstrates the potential of B. coagulans SANK 70258 to exhibit antimicrobial activity against harmful organisms in patients with ulcerative colitis, while improving the intestinal microenvironment by increasing butyrogenesis in healthy persons. KEY POINTS: • B. coagulans SANK 70258 treatment reduced colonic Enterobacteriaceae species. • B. coagulans SANK 70258 treatment enhanced butyrogenesis in healthy individuals. • B. coagulans SANK 70258 treatment increased Lachnospiraceae in healthy persons. • B. coagulans SANK 70258 improves the colonic microenvironment in ulcerative colitis.Mar. 2020, Applied microbiology and biotechnology, English, International magazine[Refereed]
- Dec. 2019, Journal of Gastroenterology and Hepatology (Australia), 34(12) (12), 2158 - 2163[Refereed]Scientific journal
- Microbial production of butyrate is impaired in patients with ulcerative colitis (UC); however, this inhibition is not well understood in Japanese UC patients. Therefore, we quantitatively analyzed genes encoding butyryl-CoA:acetate CoA-transferase (but) and butyrate kinase (buk) in the gut microbiota of Japanese patients with UC and healthy volunteers (HVs). But showed higher levels than buk. Moreover, patients with UC showed significantly decreased levels of but associated with Roseburia sp./Eubacterium rectale compared with HVs. But, which is associated with Faecalibacterium sp., was maintained in patients with UC, with an unchanged relative abundance of Faecalibacterium sp. microorganisms in patients with UC compared with HVs.Oct. 2019, Bioscience of Microbiota, Food and Health, 38(4) (4), 159 - 163, English, Domestic magazine[Refereed]Scientific journal
- Background and study aims Patients who have undergone colorectal surgery for resection of cancer and benign lesions are at risk for recurrent, residual, or metachronous lesions at the anastomosis site. Surgical resection of such lesions is difficult because of adhesions, and a stoma may be required as there are risks for leakage after resection. The feasibility and safety of endoscopic submucosal dissection (ESD) for these lesions remain unknown. Therefore, this case series aimed to examine the feasibility and safety of ESD by evaluating the clinical outcomes. Patients and methods We retrospectively investigated five patients who underwent ESD by a single expert for superficial neoplastic lesions at the anastomosis site after previous colorectal surgery. Results R0 resections were achieved for all lesions. Mean procedure time was 160.6 minutes. Mean dimensions of the resected specimen and tumor were 52.4 mm and 31.8mm, respectively. None of the patients had complications or recurrence after surveillance colonoscopy 1-year post-resection. Conclusions In an expert's hands, ESD at the anastomosis site might be feasible minimally invasive treatment for superficial neoplastic lesions.Aug. 2019, Endoscopy international open, 7(8) (8), E949-E954, English, International magazine[Refereed]
- Mar. 2019, Biochemical and Biophysical Research Communications, 511(1) (1), 99 - 104, English[Refereed]Scientific journal
- Feb. 2019, Biotechnol J, EnglishConstruction of a Model Culture System of Human Colonic Microbiota to Detect Decreased Lachnospiraceae Abundance and Butyrogenesis in the Feces of Ulcerative Colitis Patients[Refereed]Scientific journal
- Compositional alteration of the gut microbiota is associated with ulcerative colitis (UC). Here, a model culture system is established for the in vitro human colonic microbiota of UC, which will be helpful for determining medical interventions. 16S ribosomal RNA sequencing confirms that UC models are successfully developed from fecal inoculum and retain the bacterial species biodiversity of UC feces. The UC models closely reproduce the microbial components and successfully preserve distinct clusters from the healthy subjects (HS), as observed in the feces. The relative abundance of bacteria belonging to the family Lachnospiraceae significantly decreases in the UC models compared to that in HS, as observed in the feces. The system detects significantly lower butyrogenesis in the UC models than that in HS, correlating with the decreased abundance of Lachnospiraceae. Interestingly, the relative abundance of Lachnospiraceae does not correlate with disease activity (defined as partial Mayo score), suggesting that Lachnospiraceae persists in UC patients at a decreased level, irrespective of the alteration in disease activity. Moreover, the system shows that administration of Clostridium butyricum MIYAIRI restores butyrogenesis in the UC model. Hence, the model detects deregulation in the intestinal environment in UC patients and may be useful for simulating the effect of probiotics.2019, Biotechnology Journal, 14(5) (5), e1800555, English, International magazine[Refereed]Scientific journal
- BACKGROUND: It is increasingly recognized that gut microbiota play a pivotal role in the development of atherosclerotic cardiovascular disease. Previously, we have reported that the abundance of genus Bacteroides is lower in patients with coronary artery disease (CAD) than in patients without CAD with coronary risk factors or in healthy volunteers. However, it remains unclear which and how specific gut bacteria contribute to the progression of atherosclerosis. METHODS: We recruited patients with CAD patients and controls without CAD with coronary risk factors. We then compared gut microbial composition using 16S ribosomal RNA gene sequencing in fecal samples to detect species with differential abundance between 2 groups. Subsequently, we used atherosclerosis-prone mice to study the mechanisms underlying the relationship between such species and atherosclerosis. RESULTS: Human fecal 16S ribosomal RNA gene sequencing revealed a significantly lower abundance of Bacteroides vulgatus and Bacteroides dorei in patients with CAD. This significant differential abundance was confirmed by quantitative polymerase chain reaction. Gavage with live B. vulgatus and B. dorei attenuated atherosclerotic lesion formation in atherosclerosis-prone mice, markedly ameliorating endotoxemia followed by decreasing gut microbial lipopolysaccharide production, effectively suppressing proinflammatory immune responses. Furthermore, fecal lipopolysaccharide levels in patients with CAD were significantly higher and negatively correlated with the abundance of B. vulgatus and B. dorei. CONCLUSIONS: Our translational research findings identify a previously unknown link between specific gut bacteria and atherosclerosis. Treatment with live B. vulgatus and B. dorei may help prevent CAD. CLINICAL TRIAL REGISTRATION: URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018051 . Unique identifier: UMIN000015703.Nov. 2018, Circulation, 138(22) (22), 2486 - 2498, English, International magazine[Refereed]Scientific journal
- A 73-year-old female with a 6-month history of progressive dysphagia and chest pain was referred to our hospital. She underwent esophagogastroduodenoscopy, which revealed abnormally strong contractions in the distal esophagus. Esophageal biopsy specimens showed massive eosinophil infiltration into the epithelium, and high-resolution manometry (HRM) also demonstrated abnormally strong contractions in the distal esophagus. Based on these results, she was diagnosed with Jackhammer esophagus (JHE) due to eosinophilic esophagitis (EoE). Treatment was started with 5 mg/day of prednisolone (PSL), and the number of peripheral blood eosinophils quickly decreased without any improvement in the patient's dysphagia. Esophageal biopsy specimens obtained after the PSL treatment showed the disappearance of eosinophils from the epithelium. However, abnormally strong contractions were still detected on HRM. Per-oral endoscopic myotomy (POEM) was performed to treat the JHE. Interestingly, the intraoperative esophageal muscle biopsy sample demonstrated massive eosinophil infiltration into the muscle layer. After the POEM, the patient's symptoms improved, and abnormal contractions were no longer detected on HRM. The current case suggests that when EoE combined with an esophageal motility disorder are refractory to steroid therapy, clinicians should be aware that motility disorders can develop due to eosinophil infiltration deep into the esophageal muscularis propria.Oct. 2018, Clinical journal of gastroenterology, 11(5) (5), 377 - 381, English, Domestic magazine[Refereed]Scientific journal
- BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) are among the most frequently prescribed medications. Side effects including an increased risk of intestinal infections have been reported. It is assumed that PPIs can increase susceptibility to enteropathogens; however, the underlying mechanisms are unknown. Here in this study, we explored whether Lansoprazole (Laz), one of the PPIs, increases the susceptibility to enteropathogens, and further investigated the mechanism of it. METHODS: Mice were administered Laz intraperitoneally once daily and orally infected with Citrobacter rodentium (C. rodentium). The establishment of intestinal infection was assessed by histology and inflammatory cytokine expression levels measured by quantitative PCR. To test whether Laz changes the intestinal environment to influence the susceptibility, intestinal pH, microbiota, metabolites and immune cell distributions were evaluated via pH measurement, 16S rRNA gene sequencing, metabolome, and flow cytometry analyses after Laz administration. RESULTS: Colitis was induced with less C. rodentium in Laz-treated mice as compared with the controls. We found that increased numbers of C. rodentium could reach the cecum following Laz administration. Laz increased pH in the stomach but not in the intestines. It induced dysbiosis and changed the metabolite content of the small intestine. However, these changes did not lead to alterations of immune cell distribution. CONCLUSIONS: Laz raised susceptibility to C. rodentium as increased numbers of the pathogen reach the site of infection. Our results suggest that it was due to increased stomach pH which allowed more peroral enteropathogens to pass the stomach, but not because of changes of intestinal environment.Apr. 2018, Digestive diseases and sciences, 63(4) (4), 881 - 889, English, International magazine[Refereed]Scientific journal
- BACKGROUND AND AIM: One of the challenges during peroral endoscopic myotomy (POEM) is ensuring the appropriate length of myotomy on the gastric side. To determine the appropriate distal end of the gastric myotomy, we focused on the two penetrating vessels (TPVs) found in the gastric cardia during POEM. In the present study, we evaluated whether the TPVs could serve as an accurate indicator of the appropriate distal end of the gastric myotomy. METHODS: All patients who underwent POEM between March and August 2016 were included for this study. When making the submucosal tunnel in the 5 o'clock direction into the stomach, two vessels penetrating through the circular muscle along the edge of oblique muscle in the cardia can be exposed. We designated these two vessels as TPVs. The myotomy was extended until the second TPVs was exposed. The anal end of the submucosal tunnel was confirmed by the double-scope POEM technique, and the length from the gastroesophageal junction to the anal side end of the myotomy was measured by the scale on the endoscope. RESULTS: Among 37 patients who underwent myotomy in the 5 o'clock position, TPVs were found in 34 patients (91.2%). Sufficient submucosal tunneling on the gastric side was confirmed by the double-scope POEM technique in these 34 patients. Median length of the gastric myotomy was 3.0 cm (range 2-4 cm). CONCLUSION: TPVs appears to be a simple and reliable indicator to determine the appropriate distal end of myotomy.Mar. 2018, Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 30(2) (2), 206 - 211, English, International magazine[Refereed]Scientific journal
- Due to the heterogeneous pathology of traumatic brain injury (TBI), the exact mechanism of how initial brain damage leads to chronic inflammation and its effects on the whole brain remain unclear. Here, we report on long-term neuroinflammation, remote from the initial injury site, even after subsiding of the original inflammatory response, in a focal TBI mouse model. The use of translocator protein-positron emission tomography in conjunction with specialised magnetic resonance imaging modalities enabled us to visualize "previously undetected areas" of spreading inflammation after focal cortical injury. These clinically available modalities further revealed the pathophysiology of thalamic neuronal degeneration occurring as resident microglia sense damage to corticothalamic neuronal tracts and become activated. The resulting microglial activation plays a major role in prolonged inflammatory processes, which are deleterious to the thalamic network. In light of the association of this mechanism with neuronal tracts, we propose it can be termed "brain injury related inflammatory projection". Our findings on multiple spatial and temporal scales provide insight into the chronic inflammation present in neurodegenerative diseases after TBI.2018, Neuroimage Clin, 20, 946 - 954, English, International magazine[Refereed]Scientific journal
- Elsevier {BV}, Jan. 2018, Pancreatology, 18(1) (1), 54 - 60, English[Refereed]Scientific journal
- Background and study aims : In order to perform peroral endoscopic myotomy (POEM) safely, retained liquid and food debris must be removed before the procedure is started. We developed a novel technique using a super-slim gastroscope, and a gastric tube to remove retained food debris in achalasia patients. In this study, the safety and efficacy of this novel technique were investigated. Patients and methods : Eleven patients with achalasia were enrolled in this study and underwent this novel method for esophageal clearance. Results: All patients had complete clearance of the retained food debris using this method. The median procedure time (range) was 13 (6 - 30) minutes. There were no serious adverse events (AEs) and one minor AE of mucosal erythema due to mucosal suctioning. Conclusion: This novel method for esophageal clearance is safe and effective in achalasia patients with large amounts of retained food debris.Jan. 2018, Endoscopy international open, 6(1) (1), E86-E89 - E89, English, International magazine[Refereed]Scientific journal
- 2018, Kobe Journal of Medical Sciences, 64(4) (4), E140 - E148, EnglishShort-term and long-term outcomes of infliximab and tacrolimus treatment for moderate to severe ulcerative colitis: Retrospective observational study[Refereed]Scientific journal
- Aug. 2017, WORLD JOURNAL OF GASTROENTEROLOGY, 23(29) (29), 5422 - 5430, English[Refereed]Scientific journal
- BACKGROUND AND STUDY AIMS : Peroral endoscopic myotomy (POEM) is an evolving new treatment strategy for achalasia. Although several kinds of electrosurgical knives have been used in performing POEM, the best device has yet to be determined. The FlushKnife BT is a waterjet-emitting short needle-knife with a small ball tip (BT) that offers the potential to perform all aspects of POEM with a single device. In this study, we evaluated the safety and efficiency of the FlushKnife BT for POEM. PATIENTS AND METHODS: A total of 54 consecutive patients with achalasia and other spastic esophageal motility disorders, such as jackhammer esophagus or distal esophageal spasm, who underwent POEM between January 2016 and August 2016, were included in this retrospective study. RESULTS: The median operation time was 73.0 minutes (range 39 - 184 minutes). All procedures were completed using only the FlushKnife BT without changing to any other electrosurgical instrument. The median number of additional submucosal injections with an injection needle was 0 (range 0 - 1). Endoscopic vessel sealing was performed a mean of 3 times (range 0 - 7). The median number of bleeding episodes requiring treatment with hemostatic forceps was 0 (range 0 - 5). There were no significant adverse events. Seven of 52 patients (13.5 %) reported symptoms of gastroesophageal reflux disease such as heartburn or acid reflux at 3 month follow-up. CONCLUSIONS: The FlushKnife BT enabled POEM to be performed with very few device exchanges, either for re-injection or to control intraoperative bleeding. In this uncontrolled case series, the ability of the FlushKnife BT to perform nearly all aspects of the POEM procedure seems to make it particularly well suited to this procedure.Jul. 2017, Endoscopy international open, 5(7) (7), E663-E669 - E669, English, International magazine[Refereed]Scientific journal
- Jun. 2017, WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY, 9(6) (6), 263 - 267, English[Refereed]Scientific journal
- May 2017, SCIENCE, 356(6337) (6337), 513 - 519, English[Refereed]Scientific journal
- BACKGROUND AND AIM: Currently, endoscopic submucosal dissection (ESD) is a widely accepted standard treatment for early gastric cancer, but one challenging aspect of ESD is hemostasis. We developed a new hemostatic forceps (FD-Y0007) with the aim of achieving more effective hemostasis and investigated the hemostatic ability of the FD-Y0007 during gastric ESD in humans. METHODS: This study was a prospective randomized controlled trial, which was conducted at a cancer referral center. Sixty-six patients who were scheduled to undergo ESD were enrolled and randomly assigned to either the Coagrasper or the FD-Y0007, which was used for hemostasis throughout the case. The primary end point was the time required to obtain hemostasis, which was measured for the first episode of bleeding during each case. RESULTS: Hemostasis time for the first bleeding episode during ESD was 73.0 s for the Coagrasper and 21.5 s for the FD-Y0007 (P < 0.001). When all episodes of bleeding were included, hemostasis time was 56.8 s in the Coagrasper group and 25.5 s in FD-Y0007group (P < 0.0001). The frequency of adverse events (perforation: 3.4% vs 7.1%; delayed bleeding: 0% vs 0%) was not significantly different between the two groups. CONCLUSIONS: Compared with the Coagrasper, the FD-Y0007 efficiently reduces the hemostatic time during gastric ESD with no increase in adverse events.Apr. 2017, Journal of gastroenterology and hepatology, 32(4) (4), 846 - 851, English, International magazine[Refereed]Scientific journal
- Apr. 2017, JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 32(4) (4), 846 - 851, English[Refereed]Scientific journal
- Mar. 2017, WORLD JOURNAL OF GASTROENTEROLOGY, 23(9) (9), 1657 - 1665, English[Refereed]Scientific journal
- Mar. 2017, WORLD JOURNAL OF GASTROENTEROLOGY, 23(9) (9), 1657 - 1665, EnglishUsefulness of a novel slim type FlushKnife-BT over conventional FlushKnife-BT in esophageal endoscopic submucosal dissection[Refereed]Scientific journal
- 2017, INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, 173(1) (1), 23 - 33, English[Refereed]Scientific journal
- Elsevier {BV}, Sep. 2016, Pancreatology, 16(5) (5), 893 - 899, English[Refereed]Scientific journal
- Sep. 2016, ENDOSCOPY, 48(9) (9), 829 - 836, English[Refereed]Scientific journal
- BACKGROUND AND STUDY AIM: Endoscopic submucosal dissection (ESD) has been applied to treat early colorectal cancers. The aim of this study was to clarify the clinical course of ESD for lesions involving the ileocecal valve (ICV) by evaluating the successful resection rates, and the risk and frequency of adverse events. PATIENTS AND METHODS: The outcome of ESD on 38 ICV lesions was compared with the outcome of 132 cecal lesions that did not involve the ICV or appendiceal orifice during the same study period. The factors related to longer procedure time, postoperative stricture development, and tumor recurrence were investigated for ESD of ICV lesions. RESULTS: There was no significant difference between the ICV and non-ICV groups in the en block resection rates. The median procedure time was significantly longer in the ICV group than in the non-ICV group, with a point estimate of the difference of 37 minutes (95 % confidence interval [CI] 20.00 to 56.00; P < 0.01). None of the patients developed symptomatic post-ESD stricture or tumor recurrence. ESD procedure duration was ≥ 120 minutes in 16 lesions and < 120 minutes in 22 lesions of the ICV group. A specimen diameter of ≥ 40 mm and tumor extension into terminal ileum were factors related to a longer procedure time (odds ratio [OR] 8.40, 95 %CI 1.53 to 46.10, P = 0.01; OR 10.60, 95 %CI 2.17 to 51.40, P < 0.01, respectively). CONCLUSIONS: ICV lesions can be resected by ESD without major adverse events or causing symptomatic stricture development. However, ESD for ICV lesions should be performed only by expert endoscopists, as the procedure requires accomplished endoscopic skill and experience.Jul. 2016, Endoscopy, 48(7) (7), 639 - 45, English, International magazine[Refereed]Scientific journal
- Jul. 2016, ACTA GASTRO-ENTEROLOGICA BELGICA, 79(3) (3), 315 - 320, EnglishOptimization of steroid injection intervals for prevention of stricture after esophageal endoscopic submucosal dissection: A randomized controlled trial[Refereed]Scientific journal
- Jul. 2016, WORLD JOURNAL OF GASTROENTEROLOGY, 22(27) (27), 6268 - 6275, English[Refereed]Scientific journal
- Universa Press, 2016, Acta Gastro-Enterologica Belgica, 79(3) (3), 315 - 320, EnglishOptimization of steroid injection intervals for prevention of stricture after esophageal endoscopic submucosal dissection: A randomized controlled trialScientific journal
- 2016, Prog Biomater, 5(2) (2), 111 - 116, EnglishEvaluation of the xenobiotic reaction against hyaluronate-based bioresorbable membrane in the abdominal cavity[Refereed]Scientific journal
- Jan. 2016, ENDOSCOPY, 48(1) (1), 62 - 70, English[Refereed]Scientific journal
- A 66-year-old woman presented to us with malaise, anorexia and rectal mucous discharge, and her laboratory data showed severe hyponatremia, hypokalemia, hypochloremia and renal failure. Computed tomography revealed massive occupation of the rectum by a large tumor. Colonoscopy revealed a mucus-rich villous tumor in the rectum. As there were no other factors that could cause an electrolyte disorder, she was diagnosed with McKittrick-Wheelock syndrome (MWS). The current standard treatment for MWS is partial surgical colectomy. However, surgeries are invasive and postoperative complications sometimes become an issue. After confirming no signs of submucosal invasion of the tumor by magnifying chromoendoscopic examination, endoscopic submucosal dissection (ESD) was indicated. The tumor was completely removed en bloc without adverse events. The histology showed a mucosal adenocarcinoma containing a villous component, 24.5 x 17.0 cm in size. This removal dramatically improved the patient's symptoms and the electrolyte abnormalities without medication. Although several sessions of endoscopic balloon dilation were required to treat postoperative stricture, she has been symptom-free and had no recurrence for 4 years after treatment. We experienced a case of MWS treated by ESD instead of surgery. ESD should be feasible and beneficial for the treatment of MWS.Oct. 2015, Clinical journal of gastroenterology, 8(5) (5), 280 - 4, English, Domestic magazine[Refereed]Scientific journal
- PURPOSE: Recently, endoscopic submucosal dissection (ESD) has been applied for superficial colorectal neoplasms and the number of publications about it has been increasing, but little is known about the outcomes of colorectal ESD for the lesions > 50 mm. In this study, we evaluated the feasibility and safety of colorectal ESD for the lesions > 50 mm compared with the lesions < 50 mm. METHODS: A total of 674 superficial colorectal neoplasms in 629 patients treated by ESD at Kobe University Hospital from July 2008 to July 2013 were included in the analysis. RESULTS: The median operation time (range) in the large lesion group (≥ 5 cm) was 109 (37 to 596) minutes, and it was 55 (6 to 248) minutes in the small lesion group (< 5 cm). Median procedure speed (range) in the large lesion group was 0.28 (0.06 to 0.83) cm2/min, and it was 0.19 (0.04 to 0.83) cm2/min in the small lesion group. The en bloc resection rate and the curative resection rate in the small lesion group was 98.7% and 96.0%, and those were 95.7% and 91.4% in the large lesion group, respectively. In terms of adverse events, perforation, muscle damage, and postoperative bleeding occurred at similar frequency in both groups. CONCLUSIONS: ESD on colorectal lesions > 50 mm takes longer operation time; however, it is resected time effectively without increasing the risk of adverse events compared with smaller lesions by ESD.Jun. 2015, Surgical laparoscopy, endoscopy & percutaneous techniques, 25(3) (3), 223 - 8, English, International magazine[Refereed]Scientific journal
- BACKGROUND AND STUDY AIMS: During colorectal endoscopic submucosal dissection (ESD), the feature of a muscle layer being pulled toward a neoplastic tumor is sometimes detected. We call this feature the muscle-retracting sign (MR sign). The aim of this study was to evaluate whether the MR sign is associated with particular types of neoplastic lesions and whether it has any clinical significance for ESD sessions. PATIENTS AND METHODS: A total of 329 patients underwent ESD for 357 colorectal neoplasms. The frequency of positivity for the MR sign was evaluated in different morphologic and histopathologic types of neoplasm. The success rate of complete resection and the incidence of complications were also evaluated according to whether lesions were positive or negative for the MR sign. RESULTS: The rates of positivity for the MR sign in the various lesion types were as follows: laterally spreading tumor - granular nodular mixed type (LST-G-M), 9.6 %; laterally spreading tumor - granular homogeneous type (LST-G-H) and laterally spreading tumor - nongranular type (LST-NG), 0 %; sessile type, 41.2 %. The resection rate was 100 % (329 /329) in lesions negative for the MR sign; however, it was 64.3 % (18 /28) in lesions positive for the MR sign, which was significantly lower (P < 0.001). CONCLUSIONS: The MR sign was present only in some protruding lesions, and more importantly, it was associated with a high risk of incomplete tumor removal by ESD. Our data indicate that lesions positive for the MR sign lesions should be dissected with great caution; alternatively, based on the features of the individual case, a switch to surgery should be considered for the benefit of the patient.Jun. 2015, Endoscopy international open, 3(3) (3), E246-51 - 51, English, International magazine[Refereed]Scientific journal
- Mar. 2015, MUCOSAL IMMUNOLOGY, 8(2) (2), 279 - 295, English[Refereed]Scientific journal
- Mar. 2015, WORLD JOURNAL OF GASTROENTEROLOGY, 21(10) (10), 3121 - 3126, English[Refereed]Scientific journal
- Mar. 2015, DIGESTIVE ENDOSCOPY, 27(3) (3), 388 - 391, English[Refereed]Scientific journal
- 2015, INTERNAL MEDICINE, 54(22) (22), 2803 - 2813, English[Refereed]Scientific journal
- 2015, Clinical Journal of Gastroenterology, 8(2) (2), 103 - 7, English[Refereed]Scientific journal
- Sep. 2014, JOURNAL OF CROHNS & COLITIS, 8(9) (9), 1010 - 1021, English[Refereed]Scientific journal
- Aug. 2014, ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 555, 55 - 65, English[Refereed]Scientific journal
- May 2014, ELIFE, 3, e01949, English[Refereed]Scientific journal
- 2014, DIGESTION, 90(1) (1), 10 - 17, English[Refereed]Scientific journal
- 2014, ENDOSCOPY, 46(Suppl 1 UCTN) (Suppl 1 UCTN), E476 - E477, English[Refereed]Scientific journal
- Oct. 2012, NATURE COMMUNICATIONS, 3, 1120, English[Refereed]Scientific journal
- Nov. 2010, IMMUNITY, 33(5) (5), 791 - 803, English[Refereed]Scientific journal
- Nov. 2024, 臨床雑誌「内科」, 134(5) (5), 992 - 997IBDの診療の進め方
- Mar. 2024, IBD Research, 18(1) (1), 6 - 10小腸病変に対する有効性(1)接着分子を標的とした治療の有効性(小腸と大腸の接着因子の違いを含めて)[Invited]
- Mar. 2023, IBD Research, 17(1) (1), 34 - 40妊娠・出産を希望されるIBD患者の診療を身につける[Invited]
- Jan. 2021, 臨床消化器内科, 32(2) (2), 136 - 142潰瘍性大腸炎難治例の第一選択(2)トファシチニブを推奨する立場からIntroduction commerce magazine
- Oct. 2019, メディカル・サイエンス・ダイジェスト, 45(12) (12), 42 - 45, Japanese高性能培養装置による潰瘍性大腸炎腸内細菌叢の是正戦略構築Introduction scientific journal
- (公財)日本ビフィズス菌センター, Apr. 2019, 腸内細菌学雑誌, 33(2) (2), 105 - 105, Japanese日本人潰瘍性大腸炎患者の腸内細菌叢における2種の酪酸産生遺伝子の定量
- (株)東京医学社, Nov. 2018, 腎と透析, 85(5) (5), 629 - 634, Japanese【腎不全・透析患者さんのよろず健康相談-ビタミン、ミネラル、サプリメントと漢方薬】腸内細菌叢と尿毒症物質
- 日本生物工学会, Jul. 2017, 生物工学会誌, 95(7) (7), 397 - 400, Japanese16S rRNA遺伝子から見る腸内細菌叢の魅力Introduction scientific journal
- (株)日本メディカルセンター, May 2016, 臨床消化器内科, 31(6) (6), 633 - 640, Japanese【IBD治療のcritical point-私ならこうする】潰瘍性大腸炎 ステロイド抵抗性の見極めと治療方針 次の治療をどう使い分けるか?
- 日本臨床免疫学会, Sep. 2015, 日本臨床免疫学会会誌, 38(4) (4), 321 - 321, Japanese抗AIE-75抗体陽性IPEX様症候群を呈したIgA単独欠損症の1女性例
- Nov. 2014, JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 29, 44 - 44, EnglishFeasibility of endoscopic submucosal dissection for the treatment of colorectal neoplasms on ileocecal valveSummary international conference
- May 2014, GASTROENTEROLOGY, 146(5) (5), S12 - S12, EnglishMetabolome Analysis-Based Attempt to Discover Therapeutic Agents for Non-Alcoholic SteatohepatitisSummary international conference
- Jan. 2014, 炎症と免疫, 22(1) (1), 13 - 16, Japaneseメタボロミクスの現状と炎症/炎症性腸疾患解析への応用[Invited]Introduction scientific journal
- Sep. 2013, DIGESTIVE DISEASES AND SCIENCES, 58(9) (9), 2437 - 2437, EnglishCell Type Specific Role of MyD88 in Commensal-Dependent ColitisSummary international conference
- May 2013, JOURNAL OF IMMUNOLOGY, 190, EnglishCell type-specific role of autophagy against Citrobacter rodentium infectious colitisSummary international conference
- May 2012, NATURE MEDICINE, 18(5) (5), 654 - 656, EnglishOthers
■ Lectures, oral presentations, etc.
- 第111回日本消化器病学会総会, Apr. 2025ランチョンセミナー6 機序から見なおすJAK阻害剤
- ECCO2025- 20th Congress of European Crohn's and Colitis Organisation, Feb. 2025Clinical features of pediatric ulcerative colitis with atypical endoscopic findingsPoster presentation
- ECCO2025- 20th Congress of European Crohn's and Colitis Organisation, Feb. 2025The role of LAT1 in colitis and colitis-associated tumorigenesisPoster presentation
- 第61回日本消化器免疫学会総会, Dec. 2024ランチョンセミナー5 潰瘍性大腸炎におけるJAK阻害薬の役割と可能性
- 2024 Digestive Disease Transformation Medicine ForumUpdate of therapeutic strategy for Ulcerative Colitis in Japan[Invited]Invited oral presentation
- 2023 Digestive Disease transformation Medicine Forum, Dec. 2023The role of L-type amino acid transporter1 in the murine model or intestinal tumor ApcMin/+ mice[Invited]Invited oral presentation
- 第215回日本消化器病学会東北支部例会-第170回日本消化器内視鏡学会東北支部例会 合同支部例会, Jul. 20231. 医療は世界の共通問題:人生一回、小さい自分ができること[Invited]Keynote oral presentation
- 第109回日本消化器病学会総会, Apr. 2023潰瘍性大腸炎患者におけるCD4陽性細胞浸潤とベドリズマブの有効性との関連Public symposium
- 30th United European Gastroenterology Week, Oct. 2022Roles of L-Type amino acid transporter1 in the development of intestinal tumorsOral presentation
- 第81回日本癌学会, Oct. 2022The involvement of amino acids transports LAT1 in development of intestinal tumorsOral presentation
- The Conference of Qingdao Digestive Disease in 2022 The 11th Sino-Japan Endoscopy Symposium, Jun. 20225-aminosalicylate-intolerance (5-ASA intolerance) in patients with ulcerative colitis[Invited]Invited oral presentation
- The 10th annual meeting of Asian Organization for Crohn's and Colitis, Jun. 2022Trends of increasing incidence of 5-aminosalicylate-intolerance in patients with ulcerative colitis: an observational single-center study
- 第108回 日本消化器病学会総会, Apr. 2022腸管腫瘍の発生と細胞増殖におけるL-type amino acid transporter1 の役割とその機序の検討Public symposium
- 第107回日本消化器内視鏡学会近畿支部例会, Dec. 2021炎症性腸疾患の治療選択における内視鏡検査の意義 Nancy Indexを用いた潰瘍性大腸炎患者の再燃予測診断についてPublic symposium
- 第12回日本炎症性腸疾患学会, Nov. 2021潰瘍性大腸炎における抗インテグリンαvβ6自己抗体の検討Public symposium
- 第106回日本消化器内視鏡学会近畿支部例会, Jul. 2021潰瘍性大腸炎の病理学的評価における Nancy Index の有用性についてPublic symposium
- 第107回日本消化器病学会総会, Apr. 2021当院における潰瘍性大腸炎での5ASA不耐症の現状についてOral presentation
- 第210回日本消化器病学会東北支部例会 専門医セミナー, Feb. 2021炎症性腸疾患の免疫学 up to date[Invited]Public discourse
- 第114回日本消化器病学会近畿支部例会, Feb. 2021Lipomatous pseudohypertrophy of the pancreasの2症例Public symposium
- The 8th annual meeting of Asian Organization for Crohn's & Colitis, Dec. 2020Dose optimization of 6-mercaptopurine by monitoring serum sIL-2 receptor and IgG levels for the treatment of autoimmune enteropathyPoster presentation
- 第11回日本炎症性腸疾患学会学術集会, Dec. 2020CTLA-4欠損症に起因した自己免疫性腸症に対し6-メルカプトプリンが有用であった1例Public symposium
- 第11回日本炎症性腸疾患学会学術集会, Dec. 2020潰瘍性大腸炎のマネージメントOthers
- 日本小腸学会学術集会プログラム・抄録集, Nov. 2019, Japanese, 日本小腸学会クローン病との鑑別を要した家族性地中海熱の1例
- 日本臨床免疫学会総会プログラム・抄録集, Oct. 2019, Japanese, 日本臨床免疫学会ベーチェット病に伴う仙腸関節炎に対して抗TNFα阻害薬で治療中に、食道穿通病変と回盲部潰瘍が出現し、内科的治療で治療しえた腸管型ベーチェット病の1例
- 日本消化器病学会近畿支部例会プログラム・抄録集, Oct. 2019, Japanese, 日本消化器病学会-近畿支部ステロイドへの反応性が良好であった小腸リンパ管拡張症の1例
- The 7th annual meeting of Asian Organization for Crohn's & Colitis, Jun. 2019Pathological intestinal environmental status of ulcerative colitis detected by in vitro human colonic microbiota culture systemPoster presentation
- 日本消化器病学会近畿支部例会プログラム・抄録集, Feb. 2019, Japanese, 日本消化器病学会-近畿支部NUDT15遺伝子R139C多型を背景とし、アザチオプリンによる無顆粒球症を発症した潰瘍性大腸炎の1例
- 日本消化管学会雑誌, Feb. 2019, Japanese, (一社)日本消化管学会「炎症性腸疾患:シームレスなアプローチを目指して」Special situationにおけるコンセンサスとピットフォール 生物学的製剤投与中の炎症性腸疾患患者における妊娠・出産の経験
- 日本消化器病学会近畿支部例会プログラム・抄録集, Feb. 2019, Japanese, 日本消化器病学会-近畿支部炎症性腸疾患治療の最前線 当院におけるクローン病に対するウステキヌマブ使用例の検討
- 第70回日本生物工学会大会, Sep. 2018, Japanese, 関西大学 千里山キャンパス, Domestic conferenceIn vitro培養系ヒト腸内細菌叢モデルによる潰瘍性大腸炎患者の代謝プロファイル異常の検出Poster presentation
- European Crohn's and Colitis Organisation, Feb. 2018, English, オーストリア, ウィーン, International conferenceSuccessful detection of dysbiosis and altered short-chain-fatty acids levels in in vitro colonic microbiota culture system using faecal samples of ulcerative colitisPoster presentation
- The 8th Annual Meeting of Japanese Society for Inflammatory Bowel disease, Dec. 2017, Japanese, Japanese Society for Inflammatory Boewel Disease, 東京, Domestic conference複数の腸炎モデルマウスに対する漢方薬青黛の効果の検討Poster presentation
- The 8th Annual Meeting of Japanese Society for Inflammatory Bowel Disease, Dec. 2017, Japanese, Japanese Society for Inflammatory Bowel Disease, 東京, Domestic conference潰瘍性大腸炎(UC)に対するInfliximab(IFX)とTacrolimus(TAC)の長期予後の比較検討Poster presentation
- 25th United European Gastroenterology Week, Oct. 2017, English, United European Gastroenterology, バルセロナ, スペイン, International conferenceIncreased susceptibility to enteropathogenic bacteria by proton pump inhibitors in the murine model of food poisoningPoster presentation
- 第6回エビデンスニ基づく統合医療研究会, Sep. 2017, Japanese, エビデンスニ基づく統合医療研究会, 神戸, Domestic conference腸内細菌の身体への影響~腸内環境から築く健康~Public discourse
- 27th Annual Meeting of the Japan Cytometory Society, Jun. 2017, Japanese, 日本サイトメトリー学会, 神戸, Domestic conferenceGut microbiota and Inflammatory Bowel Disease[Invited]Invited oral presentation
- 第98回日本消化器内視鏡学会近畿支部例会, Jun. 2017, Japanese, Japan Gastroenterological Endoscopy Society, 神戸, Domestic conference腸管ベーチェット病および単純性潰瘍における抗TNFα抗体製剤の有効性と内使用的改善度に関する検討Public symposium
- The 6th China-Japan Forum on Endoscopy and The conference of Qingdao Digestive Disease 2017, Jun. 2017, English, 青島市医師会/青島大学医学部附属病院, 青島, 中国, International conferenceModification of IBD by gut flora recognition and change of intestinal microenvironment[Invited]Invited oral presentation
- The 103th General Meeting of the Japanese Society of Gastroenterology, Apr. 2017, Japanese, The Japanese Society of Gastroenterology, 東京, Domestic conferenceプロトンポンプ阻害薬による腸内環境変化と感染性腸炎への高感受性リスクの検討Public symposium
- The 44th Annual Meeting of the JSI, Nov. 2015, Japanese, 日本免疫学会, 札幌, Domestic conferenceCritical role of MyD88 signaling in CD11c+ cells in progression of intestinal tumorPoster presentation
- KSBMB International Conference 2015, May 2015, English, Korean Society for Biochemistry and Molecular Biology, Seoul, Korea, International conferenceInteractions of Host Cells, Microbiota and Its Metabolites in the Intestinal Tumor[Invited]Invited oral presentation
- University of Washington and Kobe University International Joint Symposium, Dec. 2014, English, University of Washington, Center for Education and Research in Membrane Biology and Medicine, Kobe University Graduate School of Medicine, 神戸, International conferenceHost-commensal interaction: disease and homeostasis in the gut[Invited]Invited oral presentation
- UEGW, Oct. 2014, English, UEGW, ウィーン, オーストリア, International conferenceClinical course after circumferential and sub-circumferential rectal endoscopic submucosal dissection for large rectal neoplasmsPoster presentation
- Digestive Disease Week 2014, May 2014, English, American Gastroenterological Association, Chicago, USA, International conferenceMetabolome Analysis-Based Attempt to Discover Therapeutic Agents for Non-Alcoholic SteatohepatitisOral presentation
- 第21回浜名湖シンポジウム, Dec. 2013, Japanese, ゼリア新薬工業株式会社, 浜松, Domestic conferenceCell type-specific role of MyD88 in murine model of inflammatory bowel diseaseOral presentation
- The 7th Japan & US Collaboration Conference in Gastroenterology, Nov. 2013, English, The American Gastroenterological Association, 東京, International conferenceCell type-specific role of MyD88 in commensal-dependent colitisOral presentation
- Immunology 2013, May 2013, English, The American Association of Immunologist, Hawaii, USA, International conferenceCell type-specific role of autophagy against Citrobacter rodentium infectious colitisPoster presentation
- 第111回日本消化器病学会総会, Apr. 2025ランチョンセミナー6 機序から見なおすJAK阻害剤
- 日本消化器病学会東北支部第215回例会 第179回日本消化器内視鏡学会東北支部例会医療は世界の興津問題ー人生一回、小さい自分ができることー[Invited]Keynote oral presentation
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2025 - 31 Mar. 2028潰瘍性大腸炎の個別化医療を目指す慢性炎症を呈する自然免疫系エフェクター細胞の同定
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, Apr. 2023 - Mar. 2026, Coinvestigatorプロスタグランジン合成酵素に着目したクローン病の新規治療法の開発
- 日本学術振興会, 科学研究費助成事業, 基盤研究(B), 神戸大学, 01 Apr. 2022 - 31 Mar. 2025自己抗原の同定に基づいた消化器系難病の病態解明と新しい診療体系の確立
- 日本学術振興会, 科学研究費助成事業, 挑戦的研究(萌芽), 神戸大学, Jun. 2023 - Mar. 2025, Principal investigatorロイシンセンシングによる腫瘍発生機序の解明と予防法の開発
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 01 Apr. 2020 - 31 Mar. 2023免疫チェックポイント阻害剤による免疫関連有害事象の病態解明とバイオマーカーの探索近年、各種の悪性腫瘍に対する免疫チェックポイント阻害剤の使用により、その自己免疫賦活化作用による免疫関連有害事象(immune-related adverse events: irAE)が問題となっている。 消化器内科領域では、irAEの5-10%を占めるirAE大腸炎が問題となっているが、irAE大腸炎は、自己免疫の関与が示唆される炎症性 腸疾患である潰瘍性大腸炎(ulcerative colitis: UC)と類似した内視鏡所見や臨床経過を呈することが明らかとなってきた。UCとirAEには自己免疫機序という 共通の病態が関与しているものと考え、研究を進めている。 申請者の所属している研究室では、UCに特異的な自己抗体Xをすでに確認している。またirAE大腸炎を発症した患者の血清も収集している。ELISA法を用いて、 血清中の自己抗体Xの有無について測定を行っている。またUCの自己抗原Xの類縁抗原を中心とした自己抗体の網羅的な探索についても現在計画中である。 またそれら自己抗体の臨床的意義を確認するため、現在神戸大学で免疫チェックポイント阻害剤を使用した患者の血清を前向きに収集することも開始してい る。モデルマウスを用いた実験については現在準備中である。
- 日本学術振興会, 科学研究費助成事業 基盤研究(B), 基盤研究(B), 神戸大学, 01 Apr. 2020 - 31 Mar. 2023腸内アミノ酸調整による腫瘍発生の回避とその機序の解明大腸癌は世界の癌罹患率第3位で、日本では戦後に増加し、癌死亡率女性1位、男性3位となっている。疫学的に赤肉や加工肉などが増加因子として挙げられるが、その機序は未解明である。遺伝的因子のみでは説明がつかず、環境因子の関わりが要因として推測される。本課題では、食生活と腫瘍の関わりについて科学的根拠を得ることを目的に、肉類に多く含まれるアミノ酸に着目し、アミノ酸が腸管腫瘍の発生や成長に関与するか研究を行う事とした。まず、特定のアミノ酸が役割を担う可能性を考え、20種類のアミノ酸のうち、体内で合成できない必須アミノ酸にまず着目し、必須アミノ酸の中から複数の候補を選択して90%制限食を作成しマウスに与えたところ、他のアミノ酸に比較し、ある一つのアミノ酸制限において、腫瘍発生を回避できることを見出した。この機序を解明するために、このアミノ酸を輸送することが知られているアミノ酸トランスポーターであるL-type amino acid transporter 1 (LAT1)に着目し、腸管上皮特異的にLAT1が欠損するマウスを作成に着手し、腸管組織の形成において、詳細な検討を行うこととした。更に腫瘍モデルと交配して観察をおこなったところ、LAT1欠損マウスにおいて、小腸での腫瘍の成長抑制がおこることが観察される陽性所見を得たこれらのことから、アミノ酸、その輸送体であるトランスポーターが腸管腫瘍形成に非常に重要な役割をになっているというベースのデータを確保したと考えている。
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2019 - 31 Mar. 2022脂肪性肝炎に対するBacteroides菌種の有効性の検討
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2019 - 31 Mar. 2022腸内環境の修飾による大腸癌予防法の開発
- 学術研究助成基金助成金/基盤研究(C), Apr. 2018 - Mar. 2021Competitive research funding
- 学術研究助成基金助成金/基盤研究(C), Apr. 2017 - Mar. 2020, Principal investigatorCompetitive research funding
- 科学研究費補助金/基盤研究(B), Apr. 2016 - Mar. 2019Competitive research funding
- 学術研究助成基金助成金/若手研究(B), Apr. 2013 - Mar. 2016, Principal investigatorCompetitive research funding
- 科学研究費一部基金/基盤研究(B)特設, Apr. 2013 - Mar. 2016Competitive research funding