| 1. |
Takayuki Yamamoto, Hiroshi Nakase, Kenji Watanabe, Shinichiro Shinzaki, Noritaka Takatsu, Toshimitsu Fujii, Ryuichi Okamoto, Katsuyoshi Matsuoka, Akihiro Yamada, Reiko Kunisaki, Minoru Matsuura, Hisashi Shiga, Shigeki Bamba, Yohei Mikami, Takahiro Shimoyama, Satoshi Motoya, Takehiro Torisu, Taku Kobayashi, Naoki Ohmiya, Masayuki Saruta, Koichiro Matsuda, Takayuki Matsumoto, Atsuo Maemoto, Yoko Murata, Shinichi Yoshigoe, Shinya Nagasaka, Tsutomu Yajima, Tadakazu Hisamatsu, Diagnosis and Clinical Features of Perianal Lesions in Newly Diagnosed Crohn's Disease: Subgroup Analysis from Inception Cohort Registry Study of Patients with Crohn's Disease (iCREST-CD)., Journal of Crohn's & colitis, 10.1093/ecco-jcc/jjad038, 2023.03, BACKGROUND AND AIMS: Perianal lesion is a refractory phenotype of Crohn's disease (CD) with significantly diminished quality of life. We evaluated the clinical characteristics of perianal lesions in newly diagnosed CD patients and the impact of perianal lesions on the quality of life in Japanese patients with CD. METHODS: Patients newly diagnosed with CD after June 2016 were included between December 2018 and June 2020 from the Inception Cohort Registry Study of Patients with CD (iCREST-CD). RESULTS: Perianal lesions were present in 324 (48.2%) of 672 patients with newly diagnosed CD. 71.9% (233/324) were male. The prevalence of perianal lesions was higher in patients aged |
| 2. |
Motohiro Esaki, Yutaro Ihara, Naoyuki Tominaga, Hironobu Takedomi, Nanae Tsuruoka, Takashi Akutagawa, Takahiro Yukimoto, Keisuke Kawasaki, Junji Umeno, Takehiro Torisu, Yasuhisa Sakata, Predictive factors of the clinical efficacy of ustekinumab in patients with refractory Crohn's disease: tertiary centers experience in Japan., International journal of colorectal disease, 10.1007/s00384-023-04359-z, 38, 1, 57-57, 2023.03, PURPOSE: Therapeutic efficacy of ustekinumab in the real-world data is limited in patients with refractory Crohn's disease (CD). In addition, factors predictive of better therapeutic efficacy of ustekinumab remains unsolved in CD. We aimed to evaluate therapeutic efficacy of ustekinumab in patients with refractory CD and to identify the factors associated with the efficacy of ustekinumab. METHODS: We retrospectively analyzed the clinical data of 72 patients treated with ustekinumab for refractory CD. Therapeutic efficacy was assessed at weeks 8, 26, 52, and 104 on the basis of dual remission, defined as the combination of Crohn's Disease Activity Index |
| 3. |
Keisuke Kawasaki, Takehiro Torisu, Motohiro Esaki, Makoto Eizuka, Shinichiro Kawatoko, Tomo Kumei, Minami Hirai, Masahiro Kondo, Shin Fujioka, Yuta Fuyuno, Yuichi Matsuno, Junji Umeno, Tomohiko Moriyama, Takanari Kitazono, Tamotsu Sugai, Takayuki Matsumoto, Continuous use of antithrombotic medications during peri-endoscopic submucosal dissection period for colorectal lesions: A propensity score matched study., Journal of gastroenterology and hepatology, 10.1111/jgh.16149, 2023.02, BACKGROUND AND AIM: The aim of this study was to elucidate the continuous use of antithrombotic medications during the peri-colorectal endoscopic submucosal dissection (ESD) period. METHODS: This study included 468 patients with colorectal epithelial neoplasms treated by ESD, consisting of 82 under antithrombotic medications and 386 patients without the medications. Among patients taking antithrombotic medications, antithrombotic agents were continued during the peri-ESD period. Clinical characteristics and adverse events were compared after propensity score matching. RESULTS: Before and after propensity score matching, post-colorectal ESD bleeding rate was higher in patients continuing antithrombotic medications (19.5% and 21.6%, respectively) than in those not taking antithrombotic medications (2.9% and 5.4%, respectively). In the Cox regression analysis, continuation of antithrombotic medications was associated with post-ESD bleeding risk (hazard ratio, 3.73; 95% confidence interval, 1.2-11.6; P |
| 4. |
Shoichi Nakamura, Kenoki Ohuchida, Yoshiki Ohtsubo, Yutaka Yamada, Chikanori Tsutsumi, Sho Okuda, Kyoko Hisano, Yuki Mochida, Tomohiko Shinkawa, Chika Iwamoto, Nobuhiro Torata, Yusuke Mizuuchi, Koji Shindo, Kohei Nakata, Taiki Moriyama, Takehiro Torisu, Eishi Nagai, Takashi Morisaki, Takanari Kitazono, Yoshinao Oda, Masafumi Nakamura, Single-cell transcriptome analysis reveals functional changes in tumour-infiltrating B lymphocytes after chemotherapy in oesophageal squamous cell carcinoma., Clinical and translational medicine, 10.1002/ctm2.1181, 13, 1, e1181, 2023.01, BACKGROUND: Tumour immune microenvironment is related with carcinogenesis and efficacy of immunotherapy. B cells play major roles in humoral immunity, but detailed functions of tumour-infiltrating B lymphocytes (TIL-Bs) are unknown. Therefore, our aim was to investigate the functional heterogeneity of TIL-Bs in oesophageal squamous cell carcinoma (ESCC) and lymph nodes (LNs) during chemotherapy. METHODS: Single-cell transcriptome analysis was performed on 23 specimens. We also performed immunohistochemical analysis of immunoglobulin κ C (IGKC), an antibody-secreting cell (ASC) marker, in 166 ESCC samples and evaluated the implication of IGKC in 2-year recurrence free survival (RFS) and 3-year overall survival (OS). RESULTS: A total of 81,246 cells were grouped into 24 clusters. We extracted B cell clusters based on canonical markers and identified 12 TIL-B subtypes in ESCC. We found that several functions, such as co-stimulation and CD40 signalling, were enhanced in TIL-Bs after chemotherapy. The proportion of naive B cells (NBCs) decreased and B cell activation genes were up-regulated in NBCs after chemotherapy. The proportion of ASCs in tumours increased with the loss of migratory abilities and antibody production in ASCs was promoted after chemotherapy. Differentially expressed genes up-regulated with chemotherapy in ASCs correlated with prolonged survival with oesophageal cancer (p = .028). In a metastatic LN, the ASC proportion increased and B cell differentiation was enhanced. In immunohistochemical analysis, RFS and OS of high IGKC expression cases were significantly better than those of low IGKC expression cases (RFS: p |
| 5. |
Katsuyoshi Matsuoka, Toshimitsu Fujii, Ryuichi Okamoto, Akihiro Yamada, Reiko Kunisaki, Minoru Matsuura, Kenji Watanabe, Hisashi Shiga, Noritaka Takatsu, Shigeki Bamba, Yohei Mikami, Takayuki Yamamoto, Takahiro Shimoyama, Satoshi Motoya, Takehiro Torisu, Taku Kobayashi, Naoki Ohmiya, Masayuki Saruta, Koichiro Matsuda, Takayuki Matsumoto, Hiroshi Nakase, Atsuo Maemoto, Shinichiro Shinzaki, Yoko Murata, Shinichi Yoshigoe, Ayako Sasaki, Tsutomu Yajima, Tadakazu Hisamatsu, Characteristics of adult patients newly diagnosed with Crohn's disease: interim analysis of the nation-wide inception cohort registry study of patients with Crohn's disease in Japan (iCREST-CD)., Journal of gastroenterology, 10.1007/s00535-022-01907-2, 57, 11, 867-878, 2022.11, BACKGROUND: The Inception Cohort Registry Study of Patients with Crohn's Disease aimed to clarify clinical characteristics and disease course of newly diagnosed Crohn's disease patients in Japan throughout a 4-year period. Results from an interim analysis of the largest nation-wide registry study that covers approximately 1% of Crohn's disease patient population in Japan are reported. METHODS: This prospective, observational registry study was conducted at 19 tertiary centers in Japan. Patients newly diagnosed with Crohn's disease after June 2016 (age ≥ 16 years at informed consent) were enrolled between December 17, 2018 and June 30, 2020. Patient demographics, diagnostic procedures and categories, disease location and lesion behavior (Montreal classification) at the time of diagnosis were recorded. RESULTS: Of 673 patients enrolled, 672 (99.9%) were analyzed (458: men, 214: women), male-to-female ratio: 2.1, median age at diagnosis 25 (range 13-86) years; peak age of disease diagnosis: 20-24 years. Most common disease location was L3 (ileocolonic; 60.1%). Non-stricturing, non-penetrating (B1) disease was most common behavior (62.8%); 48.9% reported perianal lesions. Notably, age-wise analysis revealed disease phenotypes varied between patients aged |
| 6. |
Shinichiro Kawatoko, Kenichi Kohashi, Takehiro Torisu, Taisuke Sasaki, Shinya Umekita, Eiji Oki, Masafumi Nakamura, Takanari Kitazono, Yoshinao Oda, Solid-type poorly differentiated adenocarcinoma of the stomach: A characteristic morphology reveals a distinctive immunoregulatory tumor microenvironment., Pathology, research and practice, 10.1016/j.prp.2022.154124, 238, 154124-154124, 2022.09, Solid-type poorly differentiated adenocarcinoma (solid-type-PDA) of the stomach is a unique histological subtype of "tubular adenocarcinoma", but little is known about its clinicopathological features, molecular pathological characteristics and immunoregulatory tumor microenvironment. Herein, we examined the immunohistochemical expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, MSH6) in 57 cases of solid-type-PDA and classified them as either MMR-deficient or -proficient (dMMR, N = 23; pMMR, N = 34), and additionally identified 18 dMMR-well-differentiated adenocarcinoma (WDA) and 34 pMMR-WDA as control groups. We analyzed and compared solid-type-PDA with WDA by evaluating the immunoexpressions of key immune pathway proteins (programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1)) and tumor-infiltrating lymphocytes (TILs) (CD8, Foxp3 and PD-1). The results reveled IDO1 was significantly more frequent in dMMR-solid-type-PDA than in dMMR-WDA (P = 0.0046). Moreover, dMMR-solid-type-PDA tended to have higher mean CD8+ and Foxp3+ TILs compared with dMMR-WDA [P = 0.0006 (CD8+) and P = 0.1061 (Foxp3+)], and IDO1-positive tended to be associated with a large number of CD8+, Foxp3+ or PD-1+ TILs in almost all tumor subtypes. PD-L1 was significantly observed in 44 % (15/34) of pMMR-solid-type-PDA compared with 18 % (6/34) of pMMR-WDA (P = 0.0344). Although they are molecularly and morphologically classified as the same chromosomal instability subtype, overall survival (OS) and disease-free-survival (DFS) in pMMR-solid-type-PDA were significantly worse than those in pMMR-WDA [P = 0.0216 (OS) and P = 0.0160 (DFS)]. Our study demonstrates that immunoexpressions of several immunoregulatory proteins and TILs are more prevalent in dMMR-solid-type-PDA, potentially a useful discovery for designing tumor treatments with immune checkpoint inhibitors or combination therapies with a PD-1/PD-L1-inhibitor and IDO1-inhibitor.. |
| 7. |
Tomohiro Nagasue, Atsushi Hirano, Takehiro Torisu, Junji Umeno, Hiroki Shibata, Tomohiko Moriyama, Keisuke Kawasaki, Shin Fujioka, Yuta Fuyuno, Yuichi Matsuno, Motohiro Esaki, Takanari Kitazono, The Compositional Structure of the Small Intestinal Microbial Community via Balloon-Assisted Enteroscopy., Digestion, 10.1159/000524023, 103, 4, 1-11, 2022.04, INTRODUCTION: An association has been found between human-gut microbiota and various diseases (e.g., metabolic disease) by analyzing fecal or colonic microbiota. Despite the importance of the small intestinal microbiota, sampling difficulties prevent its full analysis. We investigated the composition and metagenomic functions of microbiota along the small intestine and compared them with the microbiota from feces and from other gastrointestinal (GI) sites. METHODS: Mucosal samples from the six GI sites (stomach, duodenum, distal jejunum, proximal ileum, terminal ileum, and rectum) were collected under balloon-assisted enteroscopy. Fecal samples were collected from all participants. The microbial structures and metagenomic functions of the small intestinal mucosal microbiota were compared with those from feces and other GI sites using 16S ribosomal RNA gene sequencing. RESULTS: We analyzed 133 samples from 29 participants. Microbial beta diversity analysis showed that the jejunum and ileum differed significantly from the lower GI tract and the feces (p |
| 8. |
Yoshifumi Hori, Hidetaka Yamamoto, Shinichirou Kawatoko, Yui Nozaki, Takehiro Torisu, Koji Kato, Yuhki Koga, Hiroaki Miyoshi, Koichi Ohshima, Yuki Tateishi, Shotaro Nakamura, Takanari Kitazono, Yoshinao Oda, Lymphoid and myeloid proliferative disorders associated with inflammatory bowel disease: A clinicopathological study of 15 cases., Human pathology, 10.1016/j.humpath.2021.12.010, 2022.01, Lymphoproliferative disorder (LPD) can occur in patients with inflammatory bowel disease (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). On rare occasion, patients with IBD develop myeloid neoplasms; however, the frequency and clinicopathological features of IBD-associated lymphoid and myeloid proliferative disorder (LMPD) in Japanese patients is still unclear. In this study, we reviewed 2474 Japanese patients with IBD, and found that LMPD occurred in 12 (0.5%) patients with UC (n=7) or CD (n=5). Together with an additional 3 cases, we analyzed a total of 15 cases of LMPD for clinicopathological and histological features. Based on the status of using immunosuppressants such as biologics and immunomodulators, Epstein-Barr virus (EBV) infection, and histopathology, the 15 cases were classified into the Group I (high-grade LPD; n=7), Group II (low-grade LPD; n=5), and Group III (myeloid neoplasms; n=3). Most patients in Group I were undergoing strong immunosuppressive therapy, and the LPD lesions corresponded to high-grade B-cell or T/NK-cell lymphoma often with EBV infection. Discontinuation of immunosuppressive drugs alone did not resolve these LPDs; Group I patients required chemotherapy, and eventually 4 of them (57%) died of the tumor. Most cases in Group II were low-grade B-cell lymphoma without EBV infection and had an indolent clinical course with excellent prognosis. All patients in Group III developed acute myeloid leukemia (AML) during the course of CD. Two (67%) of these patients died of AML. Our study suggests that IBD-associated LMPD is very rare, but can follow an aggressive clinical course.. |
| 9. |
Katsuyoshi Ando, Mikihiro Fujiya, Kenji Watanabe, Sakiko Hiraoka, Hisashi Shiga, Shinji Tanaka, Hideki Iijima, Tsunekazu Mizushima, Taku Kobayashi, Masakazu Nagahori, Hiroki Ikeuchi, Shingo Kato, Takehiro Torisu, Kiyonori Kobayashi, Masaaki Higashiyama, Toshiro Fukui, Takashi Kagaya, Motohiro Esaki, Shunichi Yanai, Daiki Abukawa, Makoto Naganuma, Satoshi Motoya, Masayuki Saruta, Shigeki Bamba, Makoto Sasaki, Kazuhiko Uchiyama, Katsuyuki Fukuda, Hideo Suzuki, Hiroshi Nakase, Toshiaki Shimizu, Masahiro Iizuka, Mamoru Watanabe, Yasuo Suzuki, Tadakazu Hisamatsu, A nationwide survey concerning the mortality and risk of progressing severity due to arterial and venous thromboembolism in inflammatory bowel disease in Japan., Journal of gastroenterology, 10.1007/s00535-021-01829-5, 56, 12, 1062-1079, 2021.12, BACKGROUND: The mortality and risk factors of severe disease and death due to arterial and venous thromboembolism (ATE and VTE, respectively) in patients with inflammatory bowel disease (IBD) remain unclear, especially in Asia. AIMS: This study aimed to reveal the mortality and risk factors of TE in IBD patients in Japan. METHODS: In the primary surveillance, responses to questionnaires regarding the number of cases of severe TE and TE-associated death in IBD patients in a span of over the past 10 years were obtained from 32 institutions in Japan. In the secondary surveillance, detailed data about IBD patients with TE were collected. The characteristics, laboratory data, therapy status, and situation at the time of TE development were retrospectively collected, and the data were compared between the patients with and without severe TE and TE-associated death. RESULTS: The incidence of TE was 1.89% among 31,940 IBD patients. The frequencies of severe TE and TE-associated mortality were 10.7% and 1.0% among the total IBD and TE with IBD patients, respectively. The only risk factor for severe ATE and ATE-associated death was ischemic heart disease. The independent risk factors for severe VTE and VTE-associated death were age (≤ 45 years old), the site of VTE, and disease severity, with anti-TNF therapy as a potential negative risk factor. Patients with severe VTE had a high risk of developing persistent VTE and sequelae. CONCLUSION: Unlike ATE, the incidence of VTE was comparable in Asian and Western countries. Therapeutic and prophylactic strategies for managing IBD-associated TE in Asia are urgently needed.. |
| 10. |
Takahide Tanaka, Yuichi Matsuno, Takehiro Torisu, Hiroki Shibata, Atsushi Hirano, Junji Umeno, Keisuke Kawasaki, Shin Fujioka, Yuta Fuyuno, Tomohiko Moriyama, Motohiro Esaki, Takanari Kitazono, Gastric microbiota in patients with Helicobacter pylori-negative gastric MALT lymphoma., Medicine, 10.1097/MD.0000000000027287, 100, 38, e27287, 2021.09, ABSTRACT: To investigate the mucosal microbiota in the stomach of patients with Helicobacter pylori-negative mucosa-associated lymphoid tissue (MALT) lymphoma by means of metagenomic analysis.Although some gastric MALT lymphomas are associated with the presence of H. pylori, other gastric MALT lymphomas occur independently of H. pylori infection. The pathogenesis of H. pylori-negative MALT lymphoma remains unclear.Mucosal biopsy specimens were collected from the gastric body from 33 MALT lymphoma patients with gastric lesions, including both H. pylori-infection naïve patients and posteradication patients, as well as 27 control participants without H. pylori infection or cancer. Subsequently, the samples were subjected to 16S rRNA gene sequencing. Quantitative insights into microbial ecology, linear discriminant analysis effect size, and phylogenetic investigation of communities by reconstruction of unobserved states softwares were used to analyze the participants' microbiota.H. pylori-negative MALT lymphoma patients had significantly lower alpha diversity (P = .04), compared with control participants. Significant differences were evident in the microbial composition (P = .04), as determined by comparison of beta diversity between the 2 groups. Taxonomic composition analysis indicated that the genera Burkholderia and Sphingomonas were significantly more abundant in MALT lymphoma patients, while the genera Prevotella and Veillonella were less abundant. Functional microbiota prediction showed that the predicted gene pathways "replication and repair," "translation," and "nucleotide metabolism" were downregulated in MALT lymphoma patients.H. pylori-negative MALT lymphoma patients exhibited altered gastric mucosal microbial compositions, suggesting that altered microbiota might be involved in the pathogenesis of H. pylori-negative MALT lymphoma.. |
| 11. |
Yutaro Ihara, Takehiro Torisu, Kohta Miyawaki, Junji Umeno, Keisuke Kawasaki, Atsushi Hirano, Shin Fujioka, Yuta Fuyuno, Yuichi Matsuno, Takeshi Sugio, Kensuke Sasaki, Tomohiko Moriyama, Koichi Akashi, Takanari Kitazono, Ustekinumab Improves Active Crohn's Disease by Suppressing the T Helper 17 Pathway., Digestion, 10.1159/000518103, 1-10, 2021.07, BACKGROUND: Ustekinumab (UST), an antibody targeting the p40 subunit of interleukin (IL)-12 and IL-23, is effective in treating Crohn's disease (CD). To clarify the mechanism of UST, we investigated T-cell differentiation in CD patients treated with UST. METHODS: Twenty-seven patients with active CD were enrolled in this study. Seventeen patients were treated with UST, and 10 patients were treated with anti-tumor necrosis factor (TNF)-alpha therapy. The changes in the proportions of T-cell subsets after these therapies were analyzed by flow cytometry. Comprehensive gene expression changes in the colonic mucosa were also evaluated. RESULTS: The frequency of T helper (Th) 17 cells was significantly decreased in the peripheral blood of patients with active CD after UST therapy. Anti-TNF therapy had a minimal effect on Th17 cells but increased the proportion of regulatory T cells. Enrichment analysis showed the expression of genes involved in the Th17 differentiation pathway was downregulated in the colonic mucosa after UST but not anti-TNF therapy. There were no common differentially expressed genes between CD patients treated with UST and anti-TNF therapy, suggesting a clear difference in their mechanism of action. CONCLUSION: In patients with active CD, UST therapy suppressed Th17 cell differentiation both in the peripheral blood and colonic tissues.. |
| 12. |
Keisuke Kawasaki, Shotaro Nakamura, Makoto Eizuka, Yoshihito Tanaka, Tomo Kumei, Shunichi Yanai, Yosuke Toya, Jun Urushikubo, Takehiro Torisu, Tomohiko Moriyama, Junji Umeno, Tamotsu Sugai, Takayuki Matsumoto, Is barium enema examination negligible for the management of colorectal cancer? Comparison with conventional colonoscopy and magnifying colonoscopy., Japanese journal of radiology, 10.1007/s11604-021-01157-x, 2021.06, PURPOSE: The aim of this investigation was to evaluate the clinical value of barium enema (BE) examination for the management of colorectal epithelial neoplasms. METHODS: We reviewed the colonoscopy records at our institution from 2014 to 2019 and identified cases of endoscopically or surgically resected colorectal epithelial neoplasms evaluated by BE, conventional colonoscopy, magnifying narrow-band imaging colonoscopy (M-NBI), and magnifying chromoendoscopy (MCE). The yield of each modality for the diagnosis of massively submucosal invasive (mSM) colorectal cancer was evaluated by a receiver-operating characteristic analysis including the area under the curve (AUC). RESULTS: We analyzed the records of 105 patients (17 adenomas, 53 high-grade dysplasias (HGDs), and 35 cancers). Smooth surface, irregularity in depression, and eccentric deformity on the profile view with BE were observed more frequently in mSM cancers than adenomas/HGDs/slightly submucosal invasive cancers (p |
| 13. |
Shinichiro Shinzaki, Katsuyoshi Matsuoka, Hiroki Tanaka, Fuminao Takeshima, Shingo Kato, Takehiro Torisu, Yuki Ohta, Kenji Watanabe, Shiro Nakamura, Naoki Yoshimura, Taku Kobayashi, Akiko Shiotani, Fumihito Hirai, Sakiko Hiraoka, Mamoru Watanabe, Minoru Matsuura, Shohei Nishimoto, Shinta Mizuno, Hideki Iijima, Tetsuo Takehara, Tetsuji Naka, Takanori Kanai, Takayuki Matsumoto, Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study., Journal of gastroenterology, 10.1007/s00535-021-01793-0, 56, 6, 560-569, 2021.06, BACKGROUND: This multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease activity in inflammatory bowel disease (IBD). METHODS: Patients with moderate-to-severe IBD initiated on adalimumab therapy were enrolled herein. Serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCal) levels were measured at week 0, 12, 24, and 52. Colonoscopy was performed at week 0, 12, and 52 for ulcerative colitis (UC), and at week 0, 24, and 52 for Crohn's disease (CD). Endoscopic activity was assessed using the Simple Endoscopic Score for Crohn's Disease (SES-CD) for CD and the Mayo endoscopic subscore (MES) for UC. RESULTS: A total of 81 patients was enrolled. Serum LRG levels decreased along with improvements in clinical and endoscopic outcomes upon adalimumab treatment (27.4 ± 12.6 μg/ml at week 0, 15.5 ± 7.7 μg/ml at week 12, 15.7 ± 9.6 μg/ml at week 24, and 14.5 ± 6.8 μg/ml at week 52), being correlated with endoscopic activity at each time point (SES-CD: r = 0.391 at week 0, r = 0.563 at week 24, r = 0.697 at week 52; MES: r = 0.534 at week 0, r = 0.429 at week 12, r = 0.335 at week 52). Endoscopic activity better correlated with LRG compared to CRP and fCal on pooled analysis at all time points (SES-CD: LRG: r = 0.636, CRP: r = 0.402, fCal: r = 0.435; MES: LRG: r = 0.568, CRP: 0.389, fCal: r = 0.426). CONCLUSIONS: Serum LRG is a useful biomarker of endoscopic activity both in CD and UC during the adalimumab treatment.. |
| 14. |
Akira Harada, Takehiro Torisu, Shin Fujioka, Yuichiro Yoshida, Yasuharu Okamoto, Yuta Fuyuno, Atsushi Hirano, Junji Umeno, Kumiko Torisu, Tomohiko Moriyama, Motohiro Esaki, Takanari Kitazono, Risk of Rebleeding in Patients with Small Bowel Vascular Lesions., Internal medicine (Tokyo, Japan), 10.2169/internalmedicine.6341-20, 2021.06, Background With recent advances in endoscopic modalities, small bowel vascular lesions (SBVLs) are often now detected in patients with gastrointestinal bleeding. Given the high invasiveness of endoscopic treatment, it is important to select patients at high risk for bleeding. Aim To assess the risk of rebleeding in patients with SBVLs as a systemic disease rather than a gastrointestinal disease in relation to their general health. Methods We retrospectively analyzed the clinical data of 55 patients with SBVLs among patients with obscure gastrointestinal bleeding. The possible association between the clinical findings and the updated Charlson comorbidity index with rebleeding was evaluated. Results Gastrointestinal rebleeding occurred in 20 patients (36.4%) during the follow-up period. The presence of multiple comorbidities as indicated by an updated Charlson comorbidity index of ≥4 was a risk factor for rebleeding (hazard ratio, 3.64; P = 0.004). Other risk factors were arteriosclerosis of the superior mesenteric artery and multiple SBVLs. Endoscopic hemostasis and the discontinuation of antithrombotic medications were not significantly associated with rebleeding. Patients with a high updated Charlson comorbidity index had a high risk of death of causes other than gastrointestinal rebleeding. Conclusions Gastrointestinal rebleeding is not a rare condition among patients with SBVLs. Patients with poor general health may therefore have a higher risk of rebleeding.. |
| 15. |
Junji Umeno, Takayuki Matsumoto, Yuta Fuyuno, Motohiro Esaki, Takehiro Torisu, SLCO2A1 gene is the causal gene for both primary hypertrophic osteoarthropathy and hereditary chronic enteropathy., Journal of orthopaedic translation, 10.1016/j.jot.2020.12.005, 28, 10-11, 2021.05. |
| 16. |
Takehiro Torisu, Shinichi Kawano, Kohta Miyawaki, Hidetaka Yamamoto, Yutaro Ihara, Yuichi Matsuno, Kumiko Torisu, Takeshi Sugio, Kensuke Sasaki, Takashi Shimakawa, Koji Kato, Koichi Akashi, Shotaro Nakamura, Takanari Kitazono, B cell receptor signaling related to resistance to Helicobacter pylori eradication therapy in gastric diffuse large B cell lymphoma., Hematological oncology, 10.1002/hon.2816, 2020.10. |
| 17. |
Keizo Zeze, Atsushi Hirano, Takehiro Torisu, Motohiro Esaki, Tomohiko Moriyama, Junji Umeno, Keisuke Kawasaki, Shin Fujioka, Yuta Fuyuno, Yuichi Matsuno, Takanari Kitazono, Adding Thiopurine After Loss of Response to Infliximab Versus Early Combination in Treating Crohn's Disease: A Retrospective Study., Digestive diseases and sciences, 10.1007/s10620-020-06600-z, 2020.09, BACKGROUND: Although combining thiopurine with infliximab (IFX) is considered to improve the clinical efficacy of IFX when treating Crohn's disease (CD), it also increases the risk of adverse events (AEs). We compared the efficacy and safety of delayed thiopurine addition after loss of response (LOR) to IFX with the efficacy and safety of an earlier combination of thiopurine and IFX. METHODS: This retrospective study analyzed patients with CD who started IFX as a first-line biologic at Kyushu University Hospital between June 2002 and July 2018. Patients were assigned to either the early-combination (EC) group, who started IFX and thiopurine simultaneously, or the late-combination (LC) group, who were treated with IFX alone until they developed LOR. We compared the cumulative IFX continuation rates and AE incidence between the two groups. RESULTS: One hundred seventy-six patients were enrolled in this study; 49 were enrolled in the EC group, and 127 were enrolled in the LC group. Disease activity at baseline did not significantly differ between the groups, nor did the cumulative IFX continuation rates differ between the groups (P = 0.30); however, the AE rate was significantly higher in the EC group than in the LC group (38.7% vs. 21.2%; P = 0.02). The severe AE rate was also higher in the EC group than in the LC group (18.3% vs 3.1%; P = 0.001). CONCLUSION: Considering the risk-benefit balance, delayed addition of thiopurine after LOR to IFX might be an alternative strategy when using IFX to treat CD.. |
| 18. |
Masanao Nakamura, Tomonori Yano, Motohiro Esaki, Shiro Oka, Keigo Mitsui, Fumihito Hirai, Keisuke Kawasaki, Mitsuhiro Fujishiro, Takehiro Torisu, Shinji Tanaka, Katsuhiko Iwakiri, Masahiro Kishi, Takayuki Matsumoto, Hironori Yamamoto, Novel ultrathin double-balloon endoscopy for the diagnosis of small-bowel diseases: a multicenter nonrandomized study., Endoscopy, 10.1055/a-1243-0226, 2020.09, BACKGROUND: This study aimed to compare the markers of potential pancreatic injury during antegrade double-balloon endoscopy (DBE) using the newly developed ultrathin EN-580XP system and the conventional EN-580T system. METHODS: Patients who were scheduled for antegrade DBE during daily clinical practice were enrolled. Clinical background, adverse events, and laboratory data of patients were compared between those who underwent endoscopy using the EN-580XP system and those in whom the EN-580T system was used. The primary end points were pancreatic hyperamylasemia and hyperlipasemia after DBE. RESULTS: A total of 295 cases were registered. Pancreatic hyperamylasemia occurred in 2 of 92 patients (2.2 %) in the EN-580XP group and in 28 of 147 patients (19.1 %) in the EN-580 T diagnosis group (P |
| 19. |
Keisuke Kawasaki, Makoto Eizuka, Norihiko Kudara, Shunichi Yanai, Yosuke Toya, Takehiro Torisu, Junji Umeno, Shotaro Nakamura, Tamotsu Sugai, Takayuki Matsumoto, Mesenteric phlebosclerosis complicating colonic cancer treated by endoscopic submucosal dissection., Clinical journal of gastroenterology, 10.1007/s12328-020-01205-5, 2020.08, A 67-year old woman with a history of long-term Chinese herb use was admitted to our institution complaining of abdominal pain. Barium enema disclosed rigidity of throughout the proximal colon and a slightly elevated lesion in the transverse colon. Colonoscopy showed diffuse and bronze mucosa in the proximal colon, which was compatible with mesenteric phlebosclerosis. There was also a reddish, elevated lesion in the transverse colon. Magnifying colonoscopy revealed irregular microsurface and microvessels on the surface of the lesion. Under a diagnosis of intramucosal cancer, the elevated lesion was treated by endoscopic submucosal dissection. Histological examination of the resected specimen showed intramucosal well-differentiated adenocarcinoma, and fibrous thickening of the vascular wall together with collagen deposition in the submucosa. The final diagnosis was an intramucosal cancer occurring in mesenteric phlebosclerosis.. |
| 20. |
Daisuke Okamoto, Yosuke Kawai, Yoichi Kakuta, Takeo Naito, Takehiro Torisu, Atsushi Hirano, Junji Umeno, Yuta Fuyuno, Dalin Li, Takeru Nakano, Yasuhiro Izumiyama, Ryo Ichikawa, Keiichiro Hiramoto, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Hisashi Shiga, Katsushi Tokunaga, Minoru Nakamura, Motohiro Esaki, Takayuki Matsumoto, Dermot P B McGovern, Masao Nagasaki, Yoshitaka Kinouchi, Atsushi Masamune, Genetic Analysis of Ulcerative Colitis in Japanese Individuals Using Population-specific SNP Array., Inflammatory bowel diseases, 10.1093/ibd/izaa033, 26, 8, 1177-1187, 2020.07, BACKGROUND: To clarify the genetic background of ulcerative colitis (UC) in the Japanese population, we conducted a genome-wide association study (GWAS) using a population-specific single nucleotide polymorphism (SNP) array. METHODS: We performed a GWAS and replication study including 1676 UC patients and 2381 healthy controls. The probability of colectomy was compared between genotypes of rs117506082, the top hit SNP at HLA loci, by the Kaplan-Meier method. We studied serum expression of miR-622, a newly identified candidate gene, from 32 UC patients and 8 healthy controls by quantitative reverse-transcription polymerase chain reaction. RESULTS: In the GWAS, only the HLA loci showed genome-wide significant associations with UC (rs117506082, P = 6.69E-28). Seven nominally significant regions included 2 known loci, IL23R (rs76418789, P = 6.29E-7) and IRF8 (rs16940202, P = 1.03E-6), and 5 novel loci: MIR622 (rs9560575, P = 8.23E-7), 14q31 (rs117618617, P = 1.53E-6), KAT6B (rs12260609, P = 1.81E-6), PAX3-CCDC140-SGPP2 (rs7589797, P = 2.87E-6), and KCNA2 (rs118020656, P = 4.01E-6). Combined analysis revealed that IL23R p.G149R (rs76418789, P = 9.03E-11; odds ratio [OR], 0.51) had genome-wide significant association with UC. Patients with GG genotype of rs117506082 had a significantly lower probability of total colectomy than those with the GA+AA genotype (P = 1.72E-2). Serum expression of miR-622 in patients with inactive UC tended to be higher than in healthy controls and patients with active UC (inactive UC vs healthy controls, P = 3.03E-02; inactive UC vs active UC, P = 6.44E-02). CONCLUSIONS: IL23R p.G149R is a susceptibility locus for UC in Japanese individuals. The GG genotype of rs117506082 at HLA loci may predict a better clinical course.. |
| 21. |
Yoichi Kakuta, Ryo Ichikawa, Yuta Fuyuno, Atsushi Hirano, Junji Umeno, Takehiro Torisu, Kazuhiro Watanabe, Akihiro Asakura, Takeru Nakano, Yasuhiro Izumiyama, Daisuke Okamoto, Takeo Naito, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Takeshi Naito, Motohiro Esaki, Yosuke Kawai, Katsushi Tokunaga, Minoru Nakamura, Takayuki Matsumoto, Masao Nagasaki, Yoshitaka Kinouchi, Michiaki Unno, Atsushi Masamune, An Integrated Genomic and Transcriptomic Analysis Reveals Candidates of Susceptibility Genes for Crohn's Disease in Japanese Populations., Scientific reports, 10.1038/s41598-020-66951-5, 10, 1, 10236-10236, 2020.06, Expression quantitative trait locus (eQTL) analyses have enabled us to predict the function of disease susceptibility SNPs. However, eQTL for the effector memory T cells (TEM) located in the lamina propria mononuclear cells (LPMCs), which play an important role in Crohn's disease (CD), are not yet available. Thus, we conducted RNA sequencing and eQTL analyses of TEM cells located in the LPMCs from IBD patients (n = 20). Genome-wide association study (GWAS) was performed using genotyping data of 713 Japanese CD patients and 2,063 controls. We compared the results of GWAS and eQTL of TEM, and also performed a transcriptome-wide association study using eQTL from Genotype Tissue Expression project. By eQTL analyses of TEM, correlations of possible candidates were confirmed in 22,632 pairs and 2,463 genes. Among these candidates, 19 SNPs which showed significant correlation with tenascin-XA (TNXA) expression were significantly associated with CD in GWAS. By TWAS, TNFSF15 (FDR = 1.35e-13) in whole blood, ERV3-1 (FDR = 2.18e-2) in lymphocytes, and ZNF713 (FDR = 3.04e-2) in the sigmoid colon was significantly associated with CD. By conducting integration analyses using GWAS and eQTL data, we confirmed multiple gene transcripts are involved in the development of CD.. |
| 22. |
Yutaka Nagata, Junji Umeno, Takehiro Torisu, Gastric myeloid sarcoma with rapid growth., Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 10.1111/den.13776, 2020.06. |
| 23. |
Keizo Zeze, Atsushi Hirano, Takehiro Torisu, Motohiro Esaki, Hiroki Shibata, Tomohiko Moriyama, Junji Umeno, Shin Fujioka, Yasuharu Okamoto, Yuta Fuyuno, Yuichi Matsuno, Takanari Kitazono, Mucosal dysbiosis in patients with gastrointestinal follicular lymphoma, Hematological Oncology, 10.1002/hon.2717, 38, 2, 181-188, 2020.04, Because the pathogenesis of gastrointestinal follicular lymphoma (GI-FL) remains unclear, no standardized treatment strategy has been established. Of the gastrointestinal lymphomas, gastric mucosa-associated lymphoid tissue lymphomas are strongly associated with Helicobacter pylori; hence, the microbiota may be involved in GI-FL pathogenesis. However, the association between GI-FL and the microbiota remains uninvestigated. Therefore, we compared the mucosal microbiotas of GI-FL patients with those of controls to identify microbiota changes in GI-FL patients. Mucosal biopsy samples were obtained from the second portion of the duodenum from 20 GI-FL patients with duodenal lesions and 20 controls. Subsequent 16S rRNA gene sequencing was performed on these samples. QIIME pipeline and LEfSe software were used to analyze the microbiota. The GI-FL patients had significantly lower alpha diversity (P =.049) than did the controls, with significant differences in the microbial composition (P =.023) evaluated by the beta diversity metrics between the two groups. Comparing the taxonomic compositions indicated that the genera Sporomusa, Rothia, and Prevotella and the family Gemellaceae were significantly less abundant in the GI-FL patients than in the controls. GI-FL patients presented altered duodenal mucosal microbial compositions, suggesting that the microbiota might be involved in the GI-FL pathogenesis.. |
| 24. |
Keizo Zeze, Atsushi Hirano, Takehiro Torisu, Motohiro Esaki, Hiroki Shibata, Tomohiko Moriyama, Junji Umeno, Shin Fujioka, Yasuharu Okamoto, Yuta Fuyuno, Yuichi Matsuno, Takanari Kitazono, Mucosal dysbiosis in patients with gastrointestinal follicular lymphoma., Hematological oncology, 10.1002/hon.2717, 38, 2, 181-188, 2020.04, Because the pathogenesis of gastrointestinal follicular lymphoma (GI-FL) remains unclear, no standardized treatment strategy has been established. Of the gastrointestinal lymphomas, gastric mucosa-associated lymphoid tissue lymphomas are strongly associated with Helicobacter pylori; hence, the microbiota may be involved in GI-FL pathogenesis. However, the association between GI-FL and the microbiota remains uninvestigated. Therefore, we compared the mucosal microbiotas of GI-FL patients with those of controls to identify microbiota changes in GI-FL patients. Mucosal biopsy samples were obtained from the second portion of the duodenum from 20 GI-FL patients with duodenal lesions and 20 controls. Subsequent 16S rRNA gene sequencing was performed on these samples. QIIME pipeline and LEfSe software were used to analyze the microbiota. The GI-FL patients had significantly lower alpha diversity (P = .049) than did the controls, with significant differences in the microbial composition (P = .023) evaluated by the beta diversity metrics between the two groups. Comparing the taxonomic compositions indicated that the genera Sporomusa, Rothia, and Prevotella and the family Gemellaceae were significantly less abundant in the GI-FL patients than in the controls. GI-FL patients presented altered duodenal mucosal microbial compositions, suggesting that the microbiota might be involved in the GI-FL pathogenesis.. |
| 25. |
A. Harada, T. Torisu, M. Esaki, Gastrointestinal
Burkitt lymphoma showing multiple tumorous lesions in the gastrointestinal tract, Journal of Gastroenterology and Hepatology (Australia), 10.1111/jgh.14885, 35, 3, 2020.03. |
| 26. |
Yuichi Matsuno, Atsushi Hirano, Takehiro Torisu, Yasuharu Okamoto, Yuta Fuyuno, Shin Fujioka, Junji Umeno, Tomohiko Moriyama, Shuntaro Nagai, Yoshifumi Hori, Minako Fujiwara, Takanari Kitazono, Motohiro Esaki, Short-term and long-term outcomes of indigo naturalis treatment for inflammatory bowel disease, Journal of Gastroenterology and Hepatology (Australia), 10.1111/jgh.14823, 35, 3, 412-417, 2020.03. |
| 27. |
Yuichi Matsuno, Atsushi Hirano, Takehiro Torisu, Yasuharu Okamoto, Yuta Fuyuno, Shin Fujioka, Junji Umeno, Tomohiko Moriyama, Shuntaro Nagai, Yoshifumi Hori, Minako Fujiwara, Takanari Kitazono, Motohiro Esaki, Short-term and long-term outcomes of indigo naturalis treatment for inflammatory bowel disease., Journal of gastroenterology and hepatology, 10.1111/jgh.14823, 35, 3, 412-417, 2020.03, BACKGROUND AND AIM: Indigo naturalis (IN) is a traditional Chinese herbal medicine reported to be effective in inducing remission in ulcerative colitis (UC). We conducted a retrospective observational study to investigate the efficacy and safety of IN for induction and maintenance therapy in patients with inflammatory bowel disease. METHODS: Data were collected from the electric medical records of patients with inflammatory bowel disease who had started IN treatment between March 2015 and April 2017 at Kyushu University Hospital. Clinical response and remission rates were assessed based on the clinical activity index determined by Rachmilewitz index or Crohn's disease (CD) activity index. Cumulative IN continuation rates were estimated using the Kaplan-Meier method. Overall adverse events (AEs) during follow-up were also analyzed. RESULTS: Seventeen UC patients and eight CD patients were enrolled. Clinical response and remission rates at week 8 were 94.1% and 88.2% in UC patients and 37.5% and 25.0% in CD patients, respectively. Clinical remission rates, as assessed through non-responders imputation analyses at weeks 52 and 104, were 76.4% and 70.4% in UC patients and 25.0% and 25.0% in CD patients, respectively. Ten patients (40%) experienced AEs during follow-up. Three patients (12%) experienced severe AEs, including acute colitis requiring hospitalization in two patients and acute colitis with intussusception requiring surgery in one patient. CONCLUSIONS: Indigo naturalis showed favorable therapeutic efficacy in UC, whereas its therapeutic efficacy in CD appeared to be modest. The risk of severe AEs should be recognized for IN treatment.. |
| 28. |
Yoshifumi Hori, Hidetaka Yamamoto, Yui Nozaki, Takehiro Torisu, Minako Fujiwara, Kenichi Taguchi, Kenichi Nishiyama, Shotaro Nakamura, Takanari Kitazono, Yoshinao Oda, Colorectal diffuse large B-cell lymphoma
molecular subclassification and prognostic significance of immunoglobulin gene translocation, Human Pathology, 10.1016/j.humpath.2019.09.003, 96, 67-78, 2020.02. |
| 29. |
Yoshifumi Hori, Hidetaka Yamamoto, Yui Nozaki, Takehiro Torisu, Minako Fujiwara, Kenichi Taguchi, Kenichi Nishiyama, Shotaro Nakamura, Takanari Kitazono, Yoshinao Oda, Colorectal diffuse large B-cell lymphoma: molecular subclassification and prognostic significance of immunoglobulin gene translocation., Human pathology, 10.1016/j.humpath.2019.09.003, 96, 67-78, 2020.02, Primary colorectal diffuse large B-cell lymphoma (DLBCL) is rare, and its clinicopathological and genetic features are poorly understood. The aim of our study was to elucidate the frequency and prognostic significance of molecular subgroups in colorectal DLBCL. We examined 25 cases of colorectal lymphoma with DLBCL-like morphology and classified them into germinal center B-cell like (GCB)/non-GCB subgroups by immunohistochemistry (IHC) for CD10, bcl-6 and MUM1, or into double-expressor (DE)/non-DE subgroups by IHC for bcl-2 and c-myc. Translocations involving BCL2, BCL6, MYC, IGH, IGK, IGL, and MALT1 were also investigated using break-apart fluorescence in situ hybridization (FISH). The 25 cases were classified into two entities-DLBCL, not otherwise specified (NOS) (n = 23; 92%) and high grade B-cell lymphoma, double hit (n = 2; 8%)-according to the recent WHO classification. None of them showed histological evidence of Epstein-Barr virus infection or high-grade transformation from low grade B-cell lymphoma. Ten cases were GCB-type and four cases were DE-type, but these subtypes did not contribute to clinicopathological differences. Translocations involving BCL2, BCL6, MYC, IGH, IGK, IGL, and MALT1 were detected in 3 (12%), 3 (12%), 10 (40%), 14 (56%), 3 (12%), 3 (12%), and 0 (0%) of 25 cases, respectively. Of note, the presence of IGH translocation was significantly associated with better overall survival (P = .0053) and progression free survival (P = .0259). Similarly, the translocation involving at least one of the IGs (IGH, IGK, and/or IGL) was associated with more favorable prognosis in DLBCLs or even in DLBCL, NOS. This is the first report to reveal that a small subset of colorectal DLBCL corresponds to double-hit lymphoma. In addition, translocations involving at least one of the IGs may be a favorable prognostic factor in colorectal DLBCL. Testing the translocation involving rearrangement of IGs as well as MYC and BCL2/BCL6 may thus be useful for diagnosis and prognosis.. |
| 30. |
Kenji Ueki, Akihiro Tsuchimoto, Yuta Matsukuma, Kumiko Torisu, Kiichiro Fujisaki, Takehiro Torisu, Yuichi Yamada, Yoshinao Oda, Kosuke Masutani, Toshiaki Nakano, Kazuhiko Tsuruya, Takanari Kitazono, Hypocomplementemic urticarial vasculitis syndrome with gastrointestinal vasculitis and crescentic membranoproliferative glomerulonephritis without immune complex deposits., CEN case reports, 10.1007/s13730-019-00421-4, 9, 1, 30-35, 2020.02, Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a small vessel vasculitis characterized by hypocomplementemia and urticaria-like exanthema. Some cases also display abdominal pain and membranoproliferative glomerulonephritis (MPGN) with immune complex deposits. We treated a case of HUVS with biopsy-proven gastrointestinal vasculitis and atypical histological findings in a kidney biopsy. The 36-year-old Japanese man, who was previously diagnosed with diffuse panbronchiolitis, visited our hospital due to transient urticaria-like exanthema and rapid deterioration of kidney function. On admission, the skin lesion was found to be only pigmentation, showing no vasculitis by skin biopsy. In laboratory findings, renal dysfunction with hematuria and proteinuria and hypocomplementemia were observed. Gastrointestinal vasculitis was proven by endoscopy and biopsy of the mucosa. Kidney biopsy revealed MPGN with crescents. No immune complex deposits were observed by immunofluorescence or electron microscopy. Additional examination revealed high titers of anti-C1q antibody. The patient was diagnosed with HUVS and treated with corticosteroids and plasma exchange. Although renal function and gastrointestinal vasculitis partially improved, infectious pneumonia frequently recurred. His renal dysfunction began to progress again and reached end-stage kidney disease. This is the first case of HUVS with biopsy-proven gastrointestinal vasculitis and MPGN without immune complex deposits. Notably, in some case of HUVS, anti-C1q antibody may activate the alternative complement pathway without immune complex deposits, resulting in renal injury.. |
| 31. |
Takahide Tanaka, Koichi Kurahara, Takehiro Torisu, An Unusual Cause of Gastric Tumors, Gastroenterology, 10.1053/j.gastro.2019.07.047, 158, 1, e5-e6, 2020.01. |
| 32. |
Takahide Tanaka, Koichi Kurahara, Takehiro Torisu, An Unusual Cause of Gastric Tumors., Gastroenterology, 10.1053/j.gastro.2019.07.047, 158, 1, e5-e6, 2020.01. |
| 33. |
Y. Ihara, A. Hirano, S. Endo, H. Kobayashi, T. Torisu, Gastrointestinal
A case of zonisamide-induced esophageal and small intestinal injury, Journal of Gastroenterology and Hepatology (Australia), 10.1111/jgh.14685, 34, 10, 2019.10. |
| 34. |
T. Tanaka, Y. Okamoto, T. Torisu, Gastrointestinal
An elderly patient with bleeding Meckel's diverticulum treated by double-balloon endoscopy, Journal of Gastroenterology and Hepatology (Australia), 10.1111/jgh.14689, 34, 10, 2019.10. |
| 35. |
Yutaro Ihara, Takehiro Torisu, Tomohiko Moriyama, Junji Umeno, Atsushi Hirano, Yasuharu Okamoto, Yoshifumi Hori, Hidetaka Yamamoto, Takanari Kitazono, Motohiro Esaki, Endoscopic features of gastrointestinal stromal tumor in the small intestine., Intestinal research, 10.5217/ir.2018.00161, 17, 3, 398-403, 2019.07, BACKGROUND/AIMS: Gastrointestinal stromal tumor (GIST) is one of the most common types of submucosal tumors (SMTs). Because of GIST's malignant potential, it is crucial to differentiate it from other SMTs. The present study aimed to identify characteristic endoscopic findings of GISTs in the small intestine. METHODS: We reviewed the clinicopathological and endoscopic findings of 38 patients with endoscopically or surgically resected SMTs in the small intestine. SMTs were classified into GIST and non-GIST groups, and clinicopathological and endoscopic findings were compared between the 2 groups. RESULTS: Fifteen patients had GIST and 23 patients had other types of SMTs in the small intestine. Comparison of the endoscopic findings between the 2 groups revealed that dilated vessels in the surrounding mucosa were significantly more in number in the GIST group than in the non-GIST group (P |
| 36. |
Yuji Maehata, Yutaka Nagata, Tomohiko Moriyama, Yuichi Matsuno, Atsushi Hirano, Junji Umeno, Takehiro Torisu, Tatsuya Manabe, Takanari Kitazono, Motohiro Esaki, Risk of surgery in patients with stricturing type of Crohn's disease at the initial diagnosis: a single center experience., Intestinal research, 10.5217/ir.2018.00107, 17, 3, 357-364, 2019.07, BACKGROUND/AIMS: It remains uncertain which patients with stricturing-type Crohn's disease (CD) require early small bowel surgery after the initial diagnosis. We aimed to clarify clinical characteristics associated with the intervention in such condition of CD. METHODS: We retrospectively evaluated the clinical course of 53 patients with CD and small bowel strictures who were initially treated with medications after the initial diagnosis. We investigated possible associations between small bowel surgery and the following: clinical factors and radiologic findings at initial diagnosis and the types of medications administered during follow-up. RESULTS: Twenty-eight patients (53%) required small bowel resection during a median follow-up period of 5.0 years (range, 0.5-14.3 years). The cumulative incidence rates of small bowel surgery at 2, 5, and 10 years were 26.4%, 41.0%, and 63.2%, respectively. Univariate analysis indicated that obstructive symptoms (P=0.036), long-segment stricture (P |
| 37. |
Shunsuke Yamada, Hokuto Arase, Toshifumi Morishita, Akihiro Tsuchimoto, Kumiko Torisu, Takehiro Torisu, Kazuhiko Tsuruya, Toshiaki Nakano, Takanari Kitazono, Adrenal crisis presented as acute onset of hypercalcemia and hyponatremia triggered by acute pyelonephritis in a patient with partial hypopituitarism and pre-dialysis chronic kidney disease., CEN case reports, 10.1007/s13730-018-0371-9, 8, 2, 83-88, 2019.05, A 57-year-old woman with pre-dialysis chronic kidney disease (CKD) was hospitalized because of fever and fatigue. On admission, increased inflammatory response and pyuria with bacteriuria were observed. Pyelonephritis was successfully treated with antibiotics, whereas her fatigue continued and she developed progressive hypercalcemia and hyponatremia; serum sodium level, 116 mEq/L and corrected serum calcium level, 13.4 mg/dL. Plasma concentrations of adrenocorticotropic hormone and cortisol and serum luteinizing hormone were under the detection level. Although the reaction of other anterior pituitary hormones and the serum antidiuretic hormone (ADH) was preserved, the response of serum luteinizing hormone to administration of luteinizing hormone releasing hormone was impaired. Magnetic resonance imaging showed no structural abnormality in the thalamus, hypothalamus, and pituitary gland. She was diagnosed with adrenal insufficiency caused by partial hypopituitarism in concomitant with pyelonephritis. After starting hydrocortisone replacement, serum levels of sodium and calcium were rapidly normalized. This case highlights the importance of adrenal insufficiency as a differential diagnosis of hypercalcemia in patients with pre-dialysis CKD, especially when hyponatremia was concomitantly observed. Besides, infection should be considered as an important trigger for the development of latent adrenal insufficiency since it could increase the physiological demand of corticosteroid in the body. Also, CKD may enhance the magnitude of hypercalcemia since CKD patients have decreased capacity to increase urinary calcium excretion.. |
| 38. |
Yutaka Nagata, Motohiro Esaki, Moriyama Tomohiko, Atsushi Hirano, Junji Umeno, Yuji Maehata, takehiro torisu, Takayuki Matsumoto, Takanari Kitazono, Anti-tumor necrosis factor therapy decreases the risk of initial intestinal surgery after diagnosis of Crohn’s disease of inflammatory type, Journal of gastroenterology, 10.1007/s00535-018-1511-x, 54, 4, 330-338, 2019.04. |
| 39. |
Yutaka Nagata, Motohiro Esaki, Tomohiko Moriyama, Atsushi Hirano, Junji Umeno, Yuji Maehata, Takehiro Torisu, Takayuki Matsumoto, Takanari Kitazono, Anti-tumor necrosis factor therapy decreases the risk of initial intestinal surgery after diagnosis of Crohn's disease of inflammatory type., Journal of gastroenterology, 10.1007/s00535-018-1511-x, 54, 4, 330-338, 2019.04, BACKGROUND: Anti-tumor necrosis factor (TNF) therapy induces and maintains clinical remission in patients with Crohn's disease (CD). However, the effect of anti-TNF therapy on the natural course of CD remains controversial. We aimed to investigate the effect of anti-TNF therapy on the initial intestinal surgery for CD. METHODS: In this single-center retrospective cohort study, clinical course of 199 CD patients of inflammatory type at the initial diagnosis (the period between 1973 and 2014) was precisely reviewed until the end of 2016. Patients were divided into TNF and non-TNF groups based on anti-TNF agent use. After comparisons of clinical characteristics and medical treatments, propensity scores were calculated for covariates. Risk of intestinal surgery was compared by a Cox proportional hazards model using the propensity scores. The effect of immunomodulators on initial intestinal surgery was assessed in the TNF group. RESULTS: During the study period, 108 patients received anti-TNF therapy. The patients in the TNF group were diagnosed more recently, and more frequently had isolated colonic involvement, and perianal disease. Immunomodulators were more frequently used in the TNF group. Cumulative probability of initial intestinal surgery was significantly lower in the TNF group (P |
| 40. |
Yuichi Matsuno, Junji Umeno, Motohiro Esaki, Yoichiro Hirakawa, Yuta Fuyuno, Yasuharu Okamoto, Atsushi Hirano, Shigeyoshi Yasukawa, Fumihito Hirai, Toshiyuki Matsui, Shuhei Hosomi, Kenji Watanabe, Naoki Hosoe, Haruhiko Ogata, Tadakazu Hisamatsu, Shunichi Yanai, Shuji Kochi, Koichi Kurahara, Tsuneyoshi Yao, Takehiro Torisu, Takanari Kitazono, Takayuki Matsumoto, Measurement of prostaglandin metabolites is useful in diagnosis of small bowel ulcerations., World journal of gastroenterology, 10.3748/wjg.v25.i14.1753, 25, 14, 1753-1763, 2019.04, BACKGROUND: We recently reported on a hereditary enteropathy associated with a gene encoding a prostaglandin transporter and referred to as chronic enteropathy associated with SLCO2A1 gene (CEAS). Crohn's disease (CD) is a major differential diagnosis of CEAS, because these diseases share some clinical features. Therefore, there is a need to develop a convenient screening test to distinguish CEAS from CD. AIM: To examine whether prostaglandin E major urinary metabolites (PGE-MUM) can serve as a biomarker to distinguish CEAS from CD. METHODS: This was a transactional study of 20 patients with CEAS and 98 patients with CD. CEAS was diagnosed by the confirmation of homozygous or compound heterozygous mutation of SLCO2A1. We measured the concentration of PGE-MUM in spot urine by radioimmunoassay, and the concentration was compared between the two groups of patients. We also determined the optimal cut-off value of PGE-MUM to distinguish CEAS from CD by receiver operating characteristic (ROC) curve analysis. RESULTS: Twenty Japanese patients with CEAS and 98 patients with CD were enrolled. PGE-MUM concentration in patients with CEAS was significantly higher than that in patients with CD (median 102.7 vs 27.9 μg/g × Cre, P |
| 41. |
A small rectal cancer manifesting as ischemic colitis caused by a tumor embolus in the inferior mesenteric vein. |
| 42. |
Yuichi Matsuno, Junji Umeno, Motohiro Esaki, Yoichiro Hirakawa, Yuta Fuyuno, Yasuharu Okamoto, Atsushi Hirano, Shigeyoshi Yasukawa, Fumihito Hirai, Toshiyuki Matsui, Shuhei Hosomi, Kenji Watanabe, Naoki Hosoe, Haruhiko Ogata, Tadakazu Hisamatsu, Shunichi Yanai, Shuji Kochi, Koichi Kurahara, Tsuneyoshi Yao, takehiro torisu, Takanari Kitazono, Takayuki Matsumoto, Measurement of prostaglandin metabolites is useful in diagnosis of small bowel ulcerations, World Journal of Gastroenterology, 10.3748/wjg.v25.i14.1753, 25, 14, 1753-1763, 2019.01. |
| 43. |
Akira Harada, takehiro torisu, Yasuharu Okamoto, Atsushi Hirano, Junji Umeno, Moriyama Tomohiko, Ema Washio, Yuta Fuyuno, Shin Fujioka, Takanari Kitazono, Motohiro Esaki, Predictive Factors for Rebleeding after Negative Capsule Endoscopy among Patients with Overt Obscure Gastrointestinal Bleeding, Digestion, 10.1159/000496826, 2019.01. |
| 44. |
Akira Harada, takehiro torisu, Tsutomu Sakuma, Motohiro Esaki, A case of duodenal bulb involvement of Immunoglobulin G4 related disease complicated by ulcerative colitis, Digestive and Liver Disease, 10.1016/j.dld.2017.12.003, 50, 5, 2018.05. |
| 45. |
Akira Harada, Takehiro Torisu, Tsutomu Sakuma, Motohiro Esaki, A case of duodenal bulb involvement of Immunoglobulin G4 related disease complicated by ulcerative colitis., Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 10.1016/j.dld.2017.12.003, 50, 5, 515-515, 2018.05. |
| 46. |
Atsushi Hirano, Junji Umeno, Yasuharu Okamoto, Hiroki Shibata, Yoshitoshi Ogura, Tomohiko Moriyama, Takehiro Torisu, Shin Fujioka, Yuta Fuyuno, Yutaka Kawarabayasi, Takayuki Matsumoto, Takanari Kitazono, Motohiro Esaki, Comparison of the microbial community structure between inflamed and non-inflamed sites in patients with ulcerative colitis., Journal of gastroenterology and hepatology, 10.1111/jgh.14129, 2018.02, BACKGROUND AND AIM: The gut microbiota is suggested to play an important role in the pathogenesis of ulcerative colitis (UC). However, interindividual and spatial variations hamper the identification of UC-related changes. We thus investigated paired mucosa-associated microbiota obtained from both inflamed and non-inflamed sites of UC patients and corresponding sites of non-inflammatory bowel disease (IBD) controls. METHODS: Mucosal biopsies of both inflamed and non-inflamed sites were obtained from 14 patients with active UC of the left-sided or proctitis type. Paired mucosal biopsies of the corresponding sites were obtained from 14 non-IBD controls. The microbial community structure was investigated using 16S ribosomal RNA gene sequences, followed by data analysis using qiime and LEfSe softwares. RESULTS: Microbial alpha diversity in both inflamed and non-inflamed sites was significantly lower in UC patients compared with non-IBD controls. There were more microbes of the genus Cloacibacterium and the Tissierellaceae family, and there were less microbes of the genus Neisseria at the inflamed site when compared with the non-inflamed site in UC patients. Decreased abundance of the genera Prevotella, Eubacterium, Neisseria, Leptotrichia, Bilophila, Desulfovibrio, and Butyricimonas was evident at the inflamed site of UC patients compared with the corresponding site of non-IBD controls. Among these taxa, the genera Prevotella and Butyricimonas were also less abundant at the non-inflamed site of UC patients compared with the corresponding site in non-IBD controls. CONCLUSIONS: Mucosal microbial dysbiosis occurs at both inflamed and non-inflamed sites in UC patients. The taxa showing altered abundance in UC patients might mediate colonic inflammation.. |
| 47. |
Atsushi Hirano, Junji Umeno, Yasuharu Okamoto, Hiroki Shibata, Yoshitoshi Ogura, Moriyama Tomohiko, takehiro torisu, Shin Fujioka, Yuta Fuyuno, Yutaka Kawarabayasi, Takayuki Matsumoto, Takanari Kitazono, Motohiro Esaki, Comparison of the microbial community structure between inflamed and non-inflamed sites in patients with ulcerative colitis, Journal of Gastroenterology and Hepatology (Australia), 10.1111/jgh.14129, 2018.01, Background and Aim: The gut microbiota is suggested to play an important role in the pathogenesis of ulcerative colitis (UC). However, interindividual and spatial variations hamper the identification of UC-related changes. We thus investigated paired mucosa-associated microbiota obtained from both inflamed and non-inflamed sites of UC patients and corresponding sites of non-inflammatory bowel disease (IBD) controls. Methods: Mucosal biopsies of both inflamed and non-inflamed sites were obtained from 14 patients with active UC of the left-sided or proctitis type. Paired mucosal biopsies of the corresponding sites were obtained from 14 non-IBD controls. The microbial community structure was investigated using 16S ribosomal RNA gene sequences, followed by data analysis using qiime and LEfSe softwares. Results: Microbial alpha diversity in both inflamed and non-inflamed sites was significantly lower in UC patients compared with non-IBD controls. There were more microbes of the genus Cloacibacterium and the Tissierellaceae family, and there were less microbes of the genus Neisseria at the inflamed site when compared with the non-inflamed site in UC patients. Decreased abundance of the genera Prevotella, Eubacterium, Neisseria, Leptotrichia, Bilophila, Desulfovibrio, and Butyricimonas was evident at the inflamed site of UC patients compared with the corresponding site of non-IBD controls. Among these taxa, the genera Prevotella and Butyricimonas were also less abundant at the non-inflamed site of UC patients compared with the corresponding site in non-IBD controls. Conclusions: Mucosal microbial dysbiosis occurs at both inflamed and non-inflamed sites in UC patients. The taxa showing altered abundance in UC patients might mediate colonic inflammation.. |
| 48. |
Kenji Tsuchihashi, Tomoyasu Yoshihiro, Tomomi Aikawa, Kenta Nio, Kotoe Takayoshi, Taku Yokoyama, Mitsuhiro Fukata, Shuji Arita, hiroshi ariyama, Yukiko Shimizu, Yuichiro Yoshida, takehiro torisu, Motohiro Esaki, Keita Odashiro, Hitoshi Kusaba, Koichi Akashi, Eishi Baba, Metastatic esophageal cancer presenting as shock by injury of vagus nerve mimicking baroreceptor reflex
A case report, Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries, 10.1097/MD.0000000000008987, 96, 49, 2017.12, Rationale: Neurogenic shock is generally typified by spinal injury due to bone metastases in cancer patients, but continuous disturbance of the vagus nerve controlling the aortic arch baroreceptor can cause shock by a reflex response through the medulla oblongata. Patient concerns: A 43-year-old woman with dysphagia presented to our hospital. Computed tomography showed a primary tumor adjacent to and surrounding half the circumference of the descending aorta, and multiple cervical lymph node metastases, including a 55 × 35-mm lymph node overlapping the root of the left vagus nerve. Squamous esophageal cancer (T4bN3M1, stage IV) was diagnosed. Whereas shock status initially appeared soon after left cervical pain, suggesting pain-induced neutrally-mediated syncope, sustained bradycardia and hypotension occurred even after alleviation of pain by opioids. Diagnosis: Disturbance of the left vagus nerve associated with the aortic arch baroreceptor by a large left cervical lymph node metastasis was considered as the cause of shock, pathologically mimicking the baroreceptor reflex. Interventions: Systemic steroid administration was performed, and radiotherapy for both the primary site and lymph node metastasis was started 2 days after initiating steroid treatment. Outcomes: Four days after initiating steroid administration, hypotension and bradycardia were improved and stable. Lessons: Disturbance of the vagus nerve controlling the aortic arch baroreceptor should be kept in mind as a potential cause of neurogenic shock in cancer patients, through a pathological reflex mimicking the baroreceptor reflex.. |
| 49. |
Kenji Tsuchihashi, Tomoyasu Yoshihiro, Tomomi Aikawa, Kenta Nio, Kotoe Takayoshi, Taku Yokoyama, Mitsuhiro Fukata, Shuji Arita, Hiroshi Ariyama, Yukiko Shimizu, Yuichiro Yoshida, Takehiro Torisu, Motohiro Esaki, Keita Odashiro, Hitoshi Kusaba, Koichi Akashi, Eishi Baba, Metastatic esophageal cancer presenting as shock by injury of vagus nerve mimicking baroreceptor reflex: A case report., Medicine, 10.1097/MD.0000000000008987, 96, 49, e8987, 2017.12, RATIONALE: Neurogenic shock is generally typified by spinal injury due to bone metastases in cancer patients, but continuous disturbance of the vagus nerve controlling the aortic arch baroreceptor can cause shock by a reflex response through the medulla oblongata. PATIENT CONCERNS: A 43-year-old woman with dysphagia presented to our hospital. Computed tomography showed a primary tumor adjacent to and surrounding half the circumference of the descending aorta, and multiple cervical lymph node metastases, including a 55 × 35-mm lymph node overlapping the root of the left vagus nerve. Squamous esophageal cancer (T4bN3M1, stage IV) was diagnosed. Whereas shock status initially appeared soon after left cervical pain, suggesting pain-induced neutrally-mediated syncope, sustained bradycardia and hypotension occurred even after alleviation of pain by opioids. DIAGNOSIS: Disturbance of the left vagus nerve associated with the aortic arch baroreceptor by a large left cervical lymph node metastasis was considered as the cause of shock, pathologically mimicking the baroreceptor reflex. INTERVENTIONS: Systemic steroid administration was performed, and radiotherapy for both the primary site and lymph node metastasis was started 2 days after initiating steroid treatment. OUTCOMES: Four days after initiating steroid administration, hypotension and bradycardia were improved and stable. LESSONS: Disturbance of the vagus nerve controlling the aortic arch baroreceptor should be kept in mind as a potential cause of neurogenic shock in cancer patients, through a pathological reflex mimicking the baroreceptor reflex.. |
| 50. |
Shinichi Kawano, takehiro torisu, Motohiro Esaki, kumiko torisu, Yuichi Matsuno, Takanari Kitazono, Autophagy promotes degradation of internalized collagen and regulates distribution of focal adhesions to suppress cell adhesion, Biology Open, 10.1242/bio.027458, 6, 11, 1644-1653, 2017.11. |
| 51. |
Shinichi Kawano, Takehiro Torisu, Motohiro Esaki, Kumiko Torisu, Yuichi Matsuno, Takanari Kitazono, Autophagy promotes degradation of internalized collagen and regulates distribution of focal adhesions to suppress cell adhesion., Biology open, 10.1242/bio.027458, 6, 11, 1644-1653, 2017.11, Adhesion of cells to the extracellular matrix (ECM) via focal adhesions (FAs) is crucial for cell survival, migration, and differentiation. Although the regulation of FAs, including by integrins and the ECM, is important to cell behavior, how FAs are regulated is not well known. Autophagy is induced by both cell adhesion and cell detachment. Here, we showed that autophagosomes are located close to internalized collagen and paxillin, which is a well-known marker of FAs. Autophagy-deficient cells showed increased levels of internalized collagen compared with control cells. Moreover, paxillin exhibited a more peripheral distribution and the area of paxillin was increased, and adhesion-induced focal adhesion kinase signaling was impaired and adhesion was enhanced, in autophagy-deficient cells. These results suggest that autophagy suppressed cell adhesion by regulating internalized ECM and FAs.. |
| 52. |
Torisu T, Kawatoko S, Esaki M., Febrile Attacks With a Refractory Colonic Lesion., Gastroenterology. , 153, 1, 19-20, 2017.07. |
| 53. |
takehiro torisu, Shinichiro Kawatoko, Motohiro Esaki, Febrile Attacks With a Refractory Colonic Lesion, Gastroenterology, 10.1053/j.gastro.2017.01.020, 153, 1, 19-20, 2017.07. |
| 54. |
Takehiro Torisu, Shinichiro Kawatoko, Motohiro Esaki, Febrile Attacks With a Refractory Colonic Lesion., Gastroenterology, 10.1053/j.gastro.2017.01.020, 153, 1, 19-20, 2017.07. |
| 55. |
kumiko torisu, Xueli Zhang, Mari Nonaka, Takahide Kaji, Daisuke Tsuchimoto, Kosuke Kajitani, Sakumi Kunihiko, takehiro torisu, Kazuhiro Chida, Katsuo Sueishi, Michiaki Kubo, Jun Hata, Takanari Kitazono, Yutaka Kiyohara, Yusaku Nakabeppu, PKCη deficiency improves lipid metabolism and atherosclerosis in apolipoprotein E-deficient mice, Genes to Cells, 10.1111/gtc.12402, 21, 10, 1030-1048, 2016.10. |
| 56. |
Kumiko Torisu, Xueli Zhang, Mari Nonaka, Takahide Kaji, Daisuke Tsuchimoto, Kosuke Kajitani, Kunihiko Sakumi, Takehiro Torisu, Kazuhiro Chida, Katsuo Sueishi, Michiaki Kubo, Jun Hata, Takanari Kitazono, Yutaka Kiyohara, Yusaku Nakabeppu, PKCη deficiency improves lipid metabolism and atherosclerosis in apolipoprotein E-deficient mice., Genes to cells : devoted to molecular & cellular mechanisms, 10.1111/gtc.12402, 21, 10, 1030-1048, 2016.10, Genomewide association studies have shown that a nonsynonymous single nucleotide polymorphism in PRKCH is associated with cerebral infarction and atherosclerosis-related complications. We examined the role of PKCη in lipid metabolism and atherosclerosis using apolipoprotein E-deficient (Apoe-/- ) mice. PKCη expression was augmented in the aortas of mice with atherosclerosis and exclusively detected in MOMA2-positive macrophages within atherosclerotic lesions. Prkch+/+ Apoe-/- and Prkch-/- Apoe-/- mice were fed a high-fat diet (HFD), and the dyslipidemia observed in Prkch+/+ Apoe-/- mice was improved in Prkch-/- Apoe-/- mice, with a particular reduction in serum LDL cholesterol and phospholipids. Liver steatosis, which developed in Prkch+/+ Apoe-/- mice, was improved in Prkch-/- Apoe-/- mice, but glucose tolerance, adipose tissue and body weight, and blood pressure were unchanged. Consistent with improvements in LDL cholesterol, atherosclerotic lesions were decreased in HFD-fed Prkch-/- Apoe-/- mice. Immunoreactivity against 3-nitrotyrosine in atherosclerotic lesions was dramatically decreased in Prkch-/- Apoe-/- mice, accompanied by decreased necrosis and apoptosis in the lesions. ARG2 mRNA and protein levels were significantly increased in Prkch-/- Apoe-/- macrophages. These data show that PKCη deficiency improves dyslipidemia and reduces susceptibility to atherosclerosis in Apoe-/- mice, showing that PKCη plays a role in atherosclerosis development.. |
| 57. |
Shinichi kawano, Torisu Takehiro, A Rare Cause of Gastrointestinal Ulcers., Gastroenterology, Gastroenterology. 2016 Sep;151(3):403-4, 2016.09. |
| 58. |
Shinichi Kawano, takehiro torisu, Motohiro Esaki, A Rare Cause of Gastrointestinal Ulcers, Gastroenterology, 10.1053/j.gastro.2016.06.018, 151, 3, 403-404, 2016.09. |
| 59. |
Shinichi Kawano, Takehiro Torisu, Motohiro Esaki, A Rare Cause of Gastrointestinal Ulcers., Gastroenterology, 10.1053/j.gastro.2016.06.018, 151, 3, 403-4, 2016.09. |
| 60. |
Torisu Takehiro, Intact endothelial autophagy is required to maintain vascular lipid homeostasis, Aging cell, 2016.02. |
| 61. |
kumiko torisu, Krishna K. Singh, takehiro torisu, Fina Lovren, Jie Liu, Yi Pan, Adrian Quan, Azza Ramadan, Mohammed Al-Omran, Natalie Pankova, Shelley R. Boyd, Subodh Verma, Toren Finkel, Intact endothelial autophagy is required to maintain vascular lipid homeostasis, Aging Cell, 10.1111/acel.12423, 15, 1, 187-191, 2016.02. |
| 62. |
Kumiko Torisu, Krishna K Singh, Takehiro Torisu, Fina Lovren, Jie Liu, Yi Pan, Adrian Quan, Azza Ramadan, Mohammed Al-Omran, Natalie Pankova, Shelley R Boyd, Subodh Verma, Toren Finkel, Intact endothelial autophagy is required to maintain vascular lipid homeostasis., Aging cell, 10.1111/acel.12423, 15, 1, 187-91, 2016.02, The physiological role of autophagic flux within the vascular endothelial layer remains poorly understood. Here, we show that in primary endothelial cells, oxidized and native LDL stimulates autophagosome formation. Moreover, by both confocal and electron microscopy, excess native or modified LDL appears to be engulfed within autophagic structures. Transient knockdown of the essential autophagy gene ATG7 resulted in higher levels of intracellular (125) I-LDL and oxidized LDL (OxLDL) accumulation, suggesting that in endothelial cells, autophagy may represent an important mechanism to regulate excess, exogenous lipids. The physiological importance of these observations was assessed using mice containing a conditional deletion of ATG7 within the endothelium. Following acute intravenous infusion of fluorescently labeled OxLDL, mice lacking endothelial expression of ATG7 demonstrated prolonged retention of OxLDL within the retinal pigment epithelium (RPE) and choroidal endothelium of the eye. In a chronic model of lipid excess, we analyzed atherosclerotic burden in ApoE(-/-) mice with or without endothelial autophagic flux. The absence of endothelial autophagy markedly increased atherosclerotic burden. Thus, in both an acute and chronic in vivo model, endothelial autophagy appears critically important in limiting lipid accumulation within the vessel wall. As such, strategies that stimulate autophagy, or prevent the age-dependent decline in autophagic flux, might be particularly beneficial in treating atherosclerotic vascular disease.. |
| 63. |
鳥巣 剛弘, Autophagy regulates endothelial cell processing, maturation and secretion of von Willebrand factor, NATURE MEDICINE, 10.1038/nm.3288, 19, 10, 1281-+, 2013.10. |
| 64. |
Takehiro Torisu, Kumiko Torisu, In Hye Lee, Jie Liu, Daniela Malide, Christian A Combs, Xufeng S Wu, Ilsa I Rovira, Maria M Fergusson, Roberto Weigert, Patricia S Connelly, Mathew P Daniels, Masaaki Komatsu, Liu Cao, Toren Finkel, Autophagy regulates endothelial cell processing, maturation and secretion of von Willebrand factor., Nature medicine, 10.1038/nm.3288, 19, 10, 1281-7, 2013.10, Endothelial secretion of von Willebrand factor (VWF) from intracellular organelles known as Weibel-Palade bodies (WPBs) is required for platelet adhesion to the injured vessel wall. Here we demonstrate that WPBs are often found near or within autophagosomes and that endothelial autophagosomes contain abundant VWF protein. Pharmacological inhibitors of autophagy or knockdown of the essential autophagy genes Atg5 or Atg7 inhibits the in vitro secretion of VWF. Furthermore, although mice with endothelial-specific deletion of Atg7 have normal vessel architecture and capillary density, they exhibit impaired epinephrine-stimulated VWF release, reduced levels of high-molecular weight VWF multimers and a corresponding prolongation of bleeding times. Endothelial-specific deletion of Atg5 or pharmacological inhibition of autophagic flux results in a similar in vivo alteration of hemostasis. Thus, autophagy regulates endothelial VWF secretion, and transient pharmacological inhibition of autophagic flux may be a useful strategy to prevent thrombotic events.. |
| 65. |
Kotaro Ogawa, Takayuki Matsumoto, Motohiro Esaki, Takehiro Torisu, Mitsuo Iida, Profiles of circulating cytokines in patients with Crohn's disease under maintenance therapy with infliximab, Journal of Crohn's and Colitis, 10.1016/j.crohns.2011.10.010, 6, 5, 529-535, 2012.06, Background and aims: The effects of maintenance infliximab for Crohn's disease vary widely among patients. The aim of this study was to examine the cytokine profiles and to identify possible markers predictive of therapeutic effect of maintenance infliximab. Methods: Cytokine profiles of 35 Crohn's disease patients under maintenance infliximab therapy were analyzed prospectively. Blood samples were obtained prior to, and 2 and 6. weeks after infliximab infusion. Circulating cytokine values of interleukin (IL)-23, IL-17A, IL-12, IL-6, interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α) were compared according to the disease activity and therapeutic efficacy. Patients were classified into either the active or quiescent phase according to their disease activity at baseline. Patients were also divided into a sustained response group and non-sustained response group according to therapeutic efficacy of infliximab determined 2 and 6. weeks after infliximab infusion. Results: At baseline, serum levels of IL-23 (p |
| 66. |
Kotaro Ogawa, Takayuki Matsumoto, Motohiro Esaki, Takehiro Torisu, Mitsuo Iida, Profiles of circulating cytokines in patients with Crohn's disease under maintenance therapy with infliximab., Journal of Crohn's & colitis, 10.1016/j.crohns.2011.10.010, 6, 5, 529-35, 2012.06, BACKGROUND AND AIMS: The effects of maintenance infliximab for Crohn's disease vary widely among patients. The aim of this study was to examine the cytokine profiles and to identify possible markers predictive of therapeutic effect of maintenance infliximab. METHODS: Cytokine profiles of 35 Crohn's disease patients under maintenance infliximab therapy were analyzed prospectively. Blood samples were obtained prior to, and 2 and 6 weeks after infliximab infusion. Circulating cytokine values of interleukin (IL)-23, IL-17A, IL-12, IL-6, interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α) were compared according to the disease activity and therapeutic efficacy. Patients were classified into either the active or quiescent phase according to their disease activity at baseline. Patients were also divided into a sustained response group and non-sustained response group according to therapeutic efficacy of infliximab determined 2 and 6 weeks after infliximab infusion. RESULTS: At baseline, serum levels of IL-23 (p |
| 67. |
Toshihiro Ansai, Yutaka Takata, Inho Soh, Shuji Awano, Akihiro Yoshida, Kazuo Sonoki, Tomoko Hamasaki, Takehiro Torisu, Akira Sogame, Naoko Shimada, Tadamichi Takehara, Relationship between tooth loss and mortality in 80-year-old Japanese community-dwelling subjects, BMC Public Health, 10.1186/1471-2458-10-386, 10, 2010.07, Background. Findings from several studies suggest associations between tooth loss and health outcomes, including malnutrition, poor quality of life, and mortality, in older individuals. However, limited information is available regarding whether those associations remain true in very elderly subjects after adequately considering confounding factors such as sex and smoking status. Herein, we determined whether the number of teeth in 80-year-old subjects is an independent predictor of mortality. Methods. We initially contacted 1282 80-year-old community-dwelling individuals born in 1917, of whom 697 responded and participated in a baseline study, with follow-up examinations conducted 4 and 5.5 years later. Data from interviews and medical and oral examinations were obtained, and oral health was determined according to the number of teeth remaining in the oral cavity. Results. A total of 108 and 157 subjects died in 4 years and 5.5 years, respectively, after the baseline study. Tooth loss was significantly associated with mortality at age 85.5, but not at age 84, after adjusting for potential confounders. When the analysis was stratified by sex, we found a stronger association in females in follow-up examinations conducted at both 4- and 5.5 years. On the other hand, the effect of tooth loss on mortality was not significantly different between smokers and non-smokers. Conclusion. Tooth loss is a significant predictor of mortality independent of health factors, socio-economic status, and lifestyle in octogenarians, with a stronger association in females.. |
| 68. |
Toshihiro Ansai, Yutaka Takata, Inho Soh, Shuji Awano, Akihiro Yoshida, Kazuo Sonoki, Tomoko Hamasaki, Takehiro Torisu, Akira Sogame, Naoko Shimada, Tadamichi Takehara, Relationship between tooth loss and mortality in 80-year-old Japanese community-dwelling subjects., BMC public health, 10.1186/1471-2458-10-386, 10, 386-386, 2010.07, BACKGROUND: Findings from several studies suggest associations between tooth loss and health outcomes, including malnutrition, poor quality of life, and mortality, in older individuals. However, limited information is available regarding whether those associations remain true in very elderly subjects after adequately considering confounding factors such as sex and smoking status. Herein, we determined whether the number of teeth in 80-year-old subjects is an independent predictor of mortality. METHODS: We initially contacted 1282 80-year-old community-dwelling individuals born in 1917, of whom 697 responded and participated in a baseline study, with follow-up examinations conducted 4 and 5.5 years later. Data from interviews and medical and oral examinations were obtained, and oral health was determined according to the number of teeth remaining in the oral cavity. RESULTS: A total of 108 and 157 subjects died in 4 years and 5.5 years, respectively, after the baseline study. Tooth loss was significantly associated with mortality at age 85.5, but not at age 84, after adjusting for potential confounders. When the analysis was stratified by sex, we found a stronger association in females in follow-up examinations conducted at both 4- and 5.5 years. On the other hand, the effect of tooth loss on mortality was not significantly different between smokers and non-smokers. CONCLUSION: Tooth loss is a significant predictor of mortality independent of health factors, socio-economic status, and lifestyle in octogenarians, with a stronger association in females.. |
| 69. |
Yutaka Takata, Toshihiro Ansai, Inho Soh, Shuji Awano, Yutaka Yoshitake, Yasuo Kimura, Kazuo Sonoki, Shuntaro Kagiyama, Akihiro Yoshida, Ikuo Nakamichi, Tomoko Hamasaki, Takehiro Torisu, Kuniaki Toyoshima, Tadamichi Takehara, Quality of life and physical fitness in an 85-year-old population, Archives of Gerontology and Geriatrics, 10.1016/j.archger.2009.04.005, 50, 3, 272-276, 2010.05, Since little is known about the very elderly population aged 80 years and older, we evaluated the association of quality of life (QoL) in an 85-year-old population with physical fitness measurements assessed at age 80 and 85 years. Two hundred seven individuals (90 males, 117 females) aged 85 years underwent the Short Form-36 (SF-36) questionnaires for QoL assessment and physical fitness measurements (handgrip strength, leg-extensor strength, one-leg standing time, stepping rate of legs, walking speed). In 85-year-olds, significant associations were found, by multiple regression analysis or logistic regression analysis, with adjustment for various influencing factors in QoL assessed by SF-36 with physical fitness measurements examined at the age of 85 and 80 years. Physical scales and scores in SF-36, such as physical functioning (PF), limitation in role functioning for physical reasons (role physical; RP), bodily pain (BP), and the physical component score (PCS) tended to be more tightly associated with fitness measurements than mental scales and scores such as limitation in role functioning for emotional reasons (role emotional; RE), and emotional well-being (mental health; MH), and mental component score (MCS). Three scales the general health perceptions (GH), the vitality (VT), and the social functioning (SF) consisting of both physical and mental components were associated with fitness, the extent being intermediate between physical scales and mental scales. Of the several physical fitness measurements, leg-extensor strength and the walking speed of 85-year-olds, and the stepping rate of 80-year-olds were most closely associated with QoL. In a very elderly population of 85- and 80-year-olds, significant associations were found between QoL by SF-36 and physical fitness measurements, suggesting that increases in the levels of physical fitness, even in the very elderly, can contribute to improvements in QoL.. |
| 70. |
Yutaka Takata, Toshihiro Ansai, Inho Soh, Shuji Awano, Kazuo Sonoki, Sumio Akifusa, Shuntaro Kagiyama, Tomoko Hamasaki, Takehiro Torisu, Akihiro Yoshida, Ikuo Nakamichi, Tadamichi Takehara, Serum albumin levels as an independent predictor of 4-year mortality in a community-dwelling 80-year-old population, Aging Clinical and Experimental Research, 10.1007/BF03324812, 22, 1, 31-35, 2010.02, Background and aims: Although serum albumin levels are associated with mortality in non-institutionalized elderly people under 80 years old, as well as in the institutionalized very elderly, little is known about the relationship in community-dwelling very elderly people. We, therefore, examined the association in a Japanese population of 80-year-old community residents. Methods: Serum albumin levels were measured in 672 (267 men, 405 women) out of 1282 80-year-old individuals. Over the following 4 years, the dates and causes of death were recorded from resident registration cards and official death certificates. Results: Of the above individuals, 107 subjects died (58 men, 49 women: 27 due to cancer, 27 cardiovascular disease, and 22 pneumonia). Survival rates were compared among 4 groups (highest ≥45 g/L, higher than 43-44 g/L, lower than 41-42 g/L, lowest ≤40 g/L). After adjustment for confounding factors, total death or cardiovascular death in the lowest albumin group was 3.1 times and 10.7 times more incident than in the highest albumin group, but there were no differences among groups as regards deaths due to cancer or pneumonia. Conclusion: Serum albumin levels are an independent predictor of mortality due to all-cause or cardiovascular disease, but not of mortality due to cancer or pneumonia in very elderly Japanese community residents.. |
| 71. |
Yutaka Takata, Toshihiro Ansai, Inho Soh, Shuji Awano, Kazuo Sonoki, Sumio Akifusa, Shuntaro Kagiyama, Tomoko Hamasaki, Takehiro Torisu, Akihiro Yoshida, Ikuo Nakamichi, Tadamichi Takehara, Serum albumin levels as an independent predictor of 4-year mortality in a community-dwelling 80-year-old population., Aging clinical and experimental research, 22, 1, 31-5, 2010.02, BACKGROUND AND AIMS: Although serum albumin levels are associated with mortality in non-institutionalized elderly people under 80 years old, as well as in the institutionalized very elderly, little is known about the relationship in community-dwelling very elderly people. We, therefore, examined the association in a Japanese population of 80-year-old community residents. METHODS: Serum albumin levels were measured in 672 (267 men, 405 women) out of 1282 80-year-old individuals. Over the following 4 years, the dates and causes of death were recorded from resident registration cards and official death certificates. RESULTS: Of the above individuals, 107 subjects died (58 men, 49 women: 27 due to cancer, 27 cardiovascular disease, and 22 pneumonia). Survival rates were compared among 4 groups (highest >or=45 g/L, higher than 43-44 g/L, lower than 41-42 g/L, lowest |
| 72. |
Shuntaro Kagiyama, Yutaka Takata, Toshihiro Ansai, Kiyoshi Matsumura, Inho Soh, Shuji Awano, Kazuo Sonoki, Akihiro Yoshida, Takehiro Torisu, Tomoko Hamasaki, Ikuo Nakamichi, Tadamichi Takehara, Mitsuo Iida, Does decreased diastolic blood pressure associate with increased mortality in 80-year-old japanese, Clinical and Experimental Hypertension, 10.3109/10641960903407009, 31, 8, 639-647, 2009.12, Hypertension is one of the greatest risk factors for cardiovascular disease, but its contribution to cardiovascular mortality weakens with aging. We have previously demonstrated that at the age of 80, higher systolic blood pressure (SBP) is not correlated with increased mortality in Japan. However, we did not examine in detail whether diastolic blood pressure (DBP) independently affects mortality. In the present study, 639 participants, who were 80 years old in 1997, were enrolled. The subjects were divided by their DBP [below 70 mmHg (group 1, n = 136), from 70 mmHg to 80 mmHg (group 2, n = 200), from 80 mmHg to 90 mmHg (group 3, n = 194), over 90 mmHg (group 4, n = 109)]. During the 4-year follow-up period, 90 individuals died. Cox multivariate regression analysis revealed that group 1 showed a significantly higher mortality rate than group 4 [relative risk (RR) 2.47, confidence interval (CI) 1.0-75.70, p = 0.03)]. The relative risks of deaths from cardiovascular diseases, pneumonia, and cancer tended to be higher in group 1 than in group 4, but the difference did not reach statistical significance. These results suggest that decreased DBP is associated with higher mortality in the Japanese elderly.. |
| 73. |
Shuntaro Kagiyama, Yutaka Takata, Toshihiro Ansai, Kiyoshi Matsumura, Inho Soh, Shuji Awano, Kazuo Sonoki, Akihiro Yoshida, Takehiro Torisu, Tomoko Hamasaki, Ikuo Nakamichi, Tadamichi Takehara, Mitsuo Iida, Does decreased diastolic blood pressure associate with increased mortality in 80-year-old Japanese?, Clinical and experimental hypertension (New York, N.Y. : 1993), 10.3109/10641960903407009, 31, 8, 639-47, 2009.11, Hypertension is one of the greatest risk factors for cardiovascular disease, but its contribution to cardiovascular mortality weakens with aging. We have previously demonstrated that at the age of 80, higher systolic blood pressure (SBP) is not correlated with increased mortality in Japan. However, we did not examine in detail whether diastolic blood pressure (DBP) independently affects mortality. In the present study, 639 participants, who were 80 years old in 1997, were enrolled. The subjects were divided by their DBP [below 70 mmHg (group 1, n = 136), from 70 mmHg to 80 mmHg (group 2, n = 200), from 80 mmHg to 90 mmHg (group 3, n = 194), over 90 mmHg (group 4, n = 109)]. During the 4-year follow-up period, 90 individuals died. Cox multivariate regression analysis revealed that group 1 showed a significantly higher mortality rate than group 4 [relative risk (RR) 2.47, confidence interval (CI) 1.07-5.70, p = 0.03)]. The relative risks of deaths from cardiovascular diseases, pneumonia, and cancer tended to be higher in group 1 than in group 4, but the difference did not reach statistical significance. These results suggest that decreased DBP is associated with higher mortality in the Japanese elderly.. |
| 74. |
Takehiro Torisu, Yutaka Takata, Toshihiro Ansai, Takayuki Matsumoto, Kazuo Sonoki, Inho Soh, Shuji Awano, Akihiro Yoshida, Tomoko Hamasaki, Shuntaro Kagiyama, Ikuo Nakamichi, Tomoko Ohsumi, Kuniaki Toyoshima, Tatsuji Nishihara, Mitsuo Iida, Tadamichi Takehara, Possible association of atrophic gastritis and arterial stiffness in healthy middle-aged Japanese., Journal of atherosclerosis and thrombosis, 16, 5, 691-7, 2009.10, AIM: Helicobacter pylori (HP) has been implicated as a risk factor for cardiovascular and atherosclerotic diseases. Arterial stiffness determined by pulse wave velocity (PWV) or the cardio-ankle vascular index (CAVI) has been shown to be higher in HP-positive subjects than in HP-negative subjects; however, this result has been observed only in young subjects. The aim of the study was to investigate the possible correlation between HP infection and PWV or CAVI in middle-aged subjects. METHODS: We measured brachial-ankle PWV (baPWV), CAVI, metabolism markers, pepsinogens (PGs) and IgG antibody to HP in 343 individuals aged either 60 or 65 year old. Atrophic gastritis (AG) was diagnosed based on the values of PGs. RESULTS: baPWV and CAVI were significantly higher in the AG-positive group than in the AG-negative group even after adjusting for possible confounding factors (baPWVc; 16.63+/-3.50 vs. 15.59+/-3.47 p=0.010, CAVIc; 8.59+/-1.20 vs. 8.27+/-1.19 p=0.022). baPWV and CAVI values tended to be higher in the HP-positive group than in the HP-negative group. High-density lipoprotein (HDL) cholesterol level and the adiponectin level were lower in the AG-positive group than in the AG-negative group. CONCLUSION: There may be an association between atrophic gastritis and atherosclerosis in middle-aged subjects.. |
| 75. |
Takehiro Torisu, Yutaka Takata, Toshihiro Ansai, Inho Soh, Shuji Awano, Kazuo Sonoki, Shuntaro Kagiyama, Ikuo Nakamichi, Akihiro Yoshida, Tomoko Hamasaki, Takayuki Matsumoto, Mitsuo Iida, Tadamichi Takehara, IgA level is associated with risk for mortality in an eighty-year-old population, Gerontology, 10.1159/000162260, 55, 2, 179-185, 2009.03, Background: Immunoglobulin levels are elevated in the older people. However, it is unknown whether these levels are related to mortality. Object: To evaluate the association between immunoglobulin levels and mortality. Methods: The study population included 697 individuals (277 males and 420 females) of 1,282 eighty-year-old individuals residing in the Fukuoka prefecture, Japan. The participants were followed for 4 years after the baseline examination. Results: The hyper-IgA group, defined as a serum IgA level >400 mg/dl, had high mortality using Kaplan-Meier analysis (log rank, p = 0.037). Multivariate Cox regression analyses revealed a high risk of mortality (hazard rate = 1.233, 95% confidence interval 1.109-1.491, p = 0.031) after adjusting for covariates. The high risk of mortality in the hyper-IgA group was significant in males, but not in females. Moreover, Kaplan-Meier analysis revealed that IgA was related to cancer mortality in males (log rank, p = 0.031), but not to pneumonia or cardiovascular disease. IgM and IgG levels were not related to high risk of mortality. Conclusion: Serum IgA levels appear to be a predictor of mortality, especially cancer mortality in males.. |
| 76. |
Takehiro Torisu, Yutaka Takata, Toshihiro Ansai, Takayuki Matsumoto, Kazuo Sonoki, Inho Soh, Shuji Awano, Akihiro Yoshida, Tomoko Hamasaki, Shuntaro Kagiyama, Ikuo Nakamichi, Tomoko Ohsumi, Kuniaki Toyoshima, Tatsuji Nishihara, Mitsuo Iida, Tadamichi Takehara, Possible association of atrophic gastritis and arterial stiffness in healthy middle-aged Japanese, Journal of atherosclerosis and thrombosis, 10.5551/jat.943, 16, 5, 691-697, 2009.01, Aim: Helicobacter pylori (HP) has been implicated as a risk factor for cardiovascular and atherosclerotic diseases. Arterial stiffness determined by pulse wave velocity (PWV) or the cardio-ankle vascular index (CAVI) has been shown to be higher in HP-positive subjects than in HP-negative subjects; however, this result has been observed only in young subjects. The aim of the study was to investigate the possible correlation between HP infection and PWV or CAVI in middle-aged subjects. Methods: We measured brachial-ankle PWV (baPWV), CAVI, metabolism markers, pepsinogens (PGs) and IgG antibody to HP in 343 individuals aged either 60 or 65 year old. Atrophic gastritis (AG) was diagnosed based on the values of PGs. Results: baPWV and CAVI were significantly higher in the AG-positive group than in the AG-negative group even after adjusting for possible confounding factors (baPWVc; 16.63±3.50 vs. 15.59± 3.47 p = 0.010, CAVIc; 8.59±1.20 vs. 8.27±1.19 p = 0.022). baPWV and CAVI values tended to be higher in the HP-positive group than in the HP-negative group. High-density lipoprotein (HDL) cholesterol level and the adiponectin level were lower in the AG-positive group than in the AG-negative group. Conclusion: There may be an association between atrophic gastritis and atherosclerosis in middleaged subjects.. |
| 77. |
Takehiro Torisu, Takayuki Matsumoto, Yutaka Takata, Toshihiro Ansai, Inho Soh, Shuji Awano, Ikuo Nakamichi, Shuntaro Kagiyama, Kazuo Sonoki, Akihiro Yoshida, Tomoko Hamasaki, Mitsuo Iida, Tadamichi Takehara, Atrophic gastritis, but not antibody to Helicobacter pylori, is associated with body mass index in a Japanese population, Journal of gastroenterology, 10.1007/s00535-008-2219-0, 43, 10, 762-766, 2008.11, Background: The relationship between Helicobacter pylori (HP) infection and body mass index (BMI) is controversial. Several reports have indicated that eradication of HP infection induces an increase in BMI. In contrast, epidemiological case-control studies have failed to show an association between HP infection and BMI. Therefore, we investigated whether HP and atrophic gastritis (AG) were associated with BMI. Methods: A total of 617 individuals were recruited for the measurements of BMI, serum leptin, pepsinogens (PGs) I and II, and IgG antibody to HP (HP-IgG). BMI and leptin of the subjects were compared when the subjects were stratified by HP-IgG and PGs. Results: The subjects were divided into AG-positive and AG-negative groups according to PGs (AG-positive: PG I ≤ 70 ng/ml and PG I/II ratio ≤ 3.0). BMI after adjusting for sex and age was significantly lower in the AG-positive group than in the AG-negative group (23.47 ± 3.05 vs. 24.18 ± 3.25, P = 0.010). When the subjects were divided into two groups according to HP-IgG, BMI tended to be lower in the HP-IgG-positive group, though the difference was not large. When the subjects were divided into four groups for different combinations of AG and HP-IgG, BMI was the lowest in the AG-positive and HP-IgG-negative group. Conclusions: BMI was associated with AG, as diagnosed by PGs, but not with HP infection status. These results mean that HP infection affects BMI via atrophic gastritis.. |
| 78. |
Y. Takata, T. Ansai, I. Soh, Y. Kimura, Y. Yoshitake, K. Sonoki, S. Awano, S. Kagiyama, A. Yoshida, I. Nakamichi, T. Hamasaki, T. Torisu, K. Toyoshima, T. Takehara, Physical fitness and cognitive function in an 85-year-old community-dwelling population, Gerontology, 10.1159/000129757, 54, 6, 354-360, 2008.11, Background: Little is known about the association between physical fitness and cognitive function in very elderly people (over 80 years of age). Objectives: To evaluate that relationship in 85-year-old community-dwelling individuals. Methods: Out of 207 participants (90 males, 117 females) who were 85 years old and community-dwelling, 205 completed the Mini-Mental State Examination (MMSE) for evaluating cognitive function. The numbers of subjects who completed physical fitness measurements such as hand-grip strength, isometric leg extensor strength, one-leg standing time, stepping rate, and walking speed were 198, 159, 169, 168, and 151, respectively. Results: There were significant associations in MMSE with hand-grip strength (right or left hand), isometric leg extensor strength, stepping rate, and walking speed by simple regression analysis. MMSE was still significantly associated with hand-grip strength (β = 0.305, p = 0.005 for right side; β = 0.309, p = 0.004 for left side), stepping rate (β = 0.183, p = 0.046), and walking speed (β = -0.222, p = 0.014) by multiple regression analysis after adjustments for the amount of education, gender, smoking, drinking, complication of stroke, body weight, body height, regular medical care, serum albumin, blood HbA1c, and marital status. By logistic regression analysis, the prevalence of a normal MMSE score (MMSE ≥24) was increased by 9% with each 1-kg increase in hand-grip strength of the left hand (OR 1.087, 95% CI 1.003-1.179, p = 0.042), and was increased by 6% with each step per 10 s in stepping rate (OR 1.060, 95% CI 1.000-1.122, p = 0.048). Conclusion: In a very elderly population of 85-year-olds, cognitive function was associated with some physical fitness measurements, independent of confounding factors.. |
| 79. |
Yutaka Takata, Toshihiro Ansai, Inho Soh, Sumio Akifusa, Kazuo Sonoki, Kiyoshi Fujisawa, Akihiro Yoshida, Shuntaro Kagiyama, Tomoko Hamasaki, Ikuo Nakamichi, Shuji Awano, Takehiro Torisu, Tadamichi Takehara, Relationship between chewing ability and high-level functional capacity in an 80-year-old population in Japan, Gerodontology, 10.1111/j.1741-2358.2007.00203.x, 25, 3, 147-154, 2008.09, Objectives: To evaluate the association between high-level functional capacity and chewing in a middle-old community-based population. Background: Although basic and instrumental activities of daily living are known to be associated with chewing ability in the elderly, an association between higher levels of competence and chewing ability has not been evaluated in the elderly. Materials and methods: The association between chewing ability using a number of different foods and high-level functional capacity by the Tokyo Metropolitan Institute of Gerontology was evaluated in 694, 80-year-old people residing in Fukuoka Prefecture, Japan. Results: A significant correlation was found, using multiple regression or logistic regression analyses adjusted for various confounding factors, between the number of total chewable foods, hard foods or moderately hard foods, and total functional capacity, instrumental activity, intellectual activity or social role ability. In contrast, the number of slightly hard foods, easily chewable foods and remaining teeth were only partly related to total functional capacity and intellectual activity. Conclusion: High-level functional capacity including intellectual activity and social role in middle-old elderly was associated with the ability to chew hard foods than to chew easily chewable foods. Maintenance of chewing ability in elderly might result in better intellectual activity and social role.. |
| 80. |
Yutaka Takata, Toshihiro Ansai, Inho Soh, Sumio Akifusa, Kazuo Sonoki, Kiyoshi Fujisawa, Akihiro Yoshida, Shuntaro Kagiyama, Tomoko Hamasaki, Ikuo Nakamichi, Shuji Awano, Takehiro Torisu, Tadamichi Takehara, Relationship between chewing ability and high-level functional capacity in an 80-year-old population in Japan., Gerodontology, 10.1111/j.1741-2358.2007.00203.x, 25, 3, 147-54, 2008.09, OBJECTIVES: To evaluate the association between high-level functional capacity and chewing in a middle-old community-based population. BACKGROUND: Although basic and instrumental activities of daily living are known to be associated with chewing ability in the elderly, an association between higher levels of competence and chewing ability has not been evaluated in the elderly. MATERIALS AND METHODS: The association between chewing ability using a number of different foods and high-level functional capacity by the Tokyo Metropolitan Institute of Gerontology was evaluated in 694, 80-year-old people residing in Fukuoka Prefecture, Japan. RESULTS: A significant correlation was found, using multiple regression or logistic regression analyses adjusted for various confounding factors, between the number of total chewable foods, hard foods or moderately hard foods, and total functional capacity, instrumental activity, intellectual activity or social role ability. In contrast, the number of slightly hard foods, easily chewable foods and remaining teeth were only partly related to total functional capacity and intellectual activity. CONCLUSION: High-level functional capacity including intellectual activity and social role in middle-old elderly was associated with the ability to chew hard foods than to chew easily chewable foods. Maintenance of chewing ability in elderly might result in better intellectual activity and social role.. |
| 81. |
Takehiro Torisu, Mako Nakaya, Satoko Watanabe, Masayuki Hashimoto, Hideyuki Yoshida, Takatoshi Chinen, Ryoko Yoshida, Fuyuki Okamoto, Toshikatsu Hanada, Kumiko Torisu, Giichi Takaesu, Takashi Kobayashi, Hideo Yasukawa, Akihiko Yoshimura, Suppressor of cytokine signaling 1 protects mice against concanavalin A-induced hepatitis by inhibiting apoptosis, Hepatology, 10.1002/hep.22214, 47, 5, 1644-1654, 2008.05, Acute liver failure is associated with significant mortality. However, the underlying pathophysiological mechanism is not yet fully understood. Suppressor of cytokine signaling-1 (SOCS1), which is a negative-feedback molecule for cytokine signaling, has been shown to be rapidly induced during liver injury. Here, using liver-specific SOCS1-conditional-knockout mice, we demonstrated that SOCS1 deletion in hepatocytes enhanced concanavalin A (ConA)-induced hepatitis, which has been shown to be dependent on activated T and natural killer T (NKT) cells. Although serum cytokine level and NKT cell activation were similar in wild-type (WT) and SOCS1-deficient mice after ConA treatment, proapoptotic signals, including signal transducers and activators of transcription 1 (STAT1) and Jun-terminal kinase (JNK) activation, were enhanced in SOCS1-deficient fivers compared with those in WT livers. SOCS1-deficient hepatocytes had higher expression of Fas antigen and were more sensitive to anti-Fas antibody-induced apoptosis than were WT hepatocytes. Furthermore, SOCS1-deficient hepatocytes were more sensitive to tumor necrosis factor (TNF)-α-induced JNK activation and apoptosis. These data indicate that SOCS1 is important to the prevention of hepatocyte apoptosis induced by Fas and TNF-α. In contrast, SOCS1 overexpression in the liver by adenoviral gene transfer prevented ConA-induced fiver injury. Conclusion: These findings indicate that SOCS1 plays important negative roles in fulminant hepatitis and that forced expression of SOCS1 is therapeutic in preventing hepatitis.. |
| 82. |
Takehiro Torisu, Mako Nakaya, Satoko Watanabe, Masayuki Hashimoto, Hideyuki Yoshida, Takatoshi Chinen, Ryoko Yoshida, Fuyuki Okamoto, Toshikatsu Hanada, Kumiko Torisu, Giichi Takaesu, Takashi Kobayashi, Hideo Yasukawa, Akihiko Yoshimura, Suppressor of cytokine signaling 1 protects mice against concanavalin A-induced hepatitis by inhibiting apoptosis., Hepatology (Baltimore, Md.), 10.1002/hep.22214, 47, 5, 1644-54, 2008.05, UNLABELLED: Acute liver failure is associated with significant mortality. However, the underlying pathophysiological mechanism is not yet fully understood. Suppressor of cytokine signaling-1 (SOCS1), which is a negative-feedback molecule for cytokine signaling, has been shown to be rapidly induced during liver injury. Here, using liver-specific SOCS1-conditional-knockout mice, we demonstrated that SOCS1 deletion in hepatocytes enhanced concanavalin A (ConA)-induced hepatitis, which has been shown to be dependent on activated T and natural killer T (NKT) cells. Although serum cytokine level and NKT cell activation were similar in wild-type (WT) and SOCS1-deficient mice after ConA treatment, proapoptotic signals, including signal transducers and activators of transcription 1 (STAT1) and Jun-terminal kinase (JNK) activation, were enhanced in SOCS1-deficient livers compared with those in WT livers. SOCS1-deficient hepatocytes had higher expression of Fas antigen and were more sensitive to anti-Fas antibody-induced apoptosis than were WT hepatocytes. Furthermore, SOCS1-deficient hepatocytes were more sensitive to tumor necrosis factor (TNF)-alpha-induced JNK activation and apoptosis. These data indicate that SOCS1 is important to the prevention of hepatocyte apoptosis induced by Fas and TNF-alpha. In contrast, SOCS1 overexpression in the liver by adenoviral gene transfer prevented ConA-induced liver injury. CONCLUSION: These findings indicate that SOCS1 plays important negative roles in fulminant hepatitis and that forced expression of SOCS1 is therapeutic in preventing hepatitis.. |
| 83. |
Kentaro Tanaka, Kenji Ichiyama, Masayuki Hashimoto, Hideyuki Yoshida, Tomohito Takimoto, Giichi Takaesu, Takehiro Torisu, Toshikatsu Hanada, Hideo Yasukawa, Satoru Fukuyama, Hiromasa Inoue, Yoichi Nakanishi, Takashi Kobayashi, Akihiko Yoshimura, Loss of suppressor of cytokine signaling 1 in helper T cells leads to defective Th17 differentiation by enhancing antagonistic effects of IFN-γ on STAT3 and Smads, Journal of Immunology, 180, 6, 3746-3756, 2008.03, Suppressor of cytokine signaling 1 (SOCS1) is an important negative regulator for cytokines; however, the role of SOCS1 in Th17 differentiation has not been clarified. We generated T cell-specific SOCS1-deficient mice and found that these mice were extremely resistant to a Th17-dependent autoimmune disease model, experimental autoimmune encephalomyelitis. SOCS1-deficient naive CD4 + T cells were predominantly differentiated into Th1 and poorly into Th17 in vitro. These phenotypes were canceled in IFN-γ-/- background, suggesting that a large amount of IFN-γ in SOCS1-deficient T cells suppressed Th17 differentiation. IL-6 plus TGF-β enhanced retinoic acid receptor-related orphan receptor (ROR)-γt expression and suppressed IFN-γ production in wild-type T cells, whereas these effects were severely impaired in SOCS1-deficient T cells. These phenotypes can be partly explained by STAT3 suppression by enhanced SOCS3 induction through hyper-STAT1 activation in SOCS1-deficient T cells. In addition, SOCS1-deficient T cells were much less sensitive to TGF-β. Suppression of Th1 differentiation by TGF-β was impaired in SOCS1-deficient T cells. TGF-β-mediated Smad transcriptional activity was severely inhibited in SOCS1-deficient cells in the presence of IFN-γ. Such impairment of TGF-γ functions were not observed in SOCS3-overexpressed cells, indicating that suppression of Smads was independent of SOCS3. Therefore, SOCS1 is necessary for Th17 differentiation by suppressing antagonistic effect of IFN-γ on both STAT3 and Smads. Induction of SOCS3 can partly explain IFN-γ-mediated STAT3 suppression, while other mechanism(s) will be involved in IFN-β-mediated Smad suppression. SOCS1-deficient T cells will be very useful to investigate the molecular mechanism for the STAT1-mediated suppression of Th17 development.. |
| 84. |
Kentaro Tanaka, Kenji Ichiyama, Masayuki Hashimoto, Hideyuki Yoshida, Tomohito Takimoto, Giichi Takaesu, Takehiro Torisu, Toshikatsu Hanada, Hideo Yasukawa, Satoru Fukuyama, Hiromasa Inoue, Yoichi Nakanishi, Takashi Kobayashi, Akihiko Yoshimura, Loss of suppressor of cytokine signaling 1 in helper T cells leads to defective Th17 differentiation by enhancing antagonistic effects of IFN-gamma on STAT3 and Smads., Journal of immunology (Baltimore, Md. : 1950), 180, 6, 3746-56, 2008.03, Suppressor of cytokine signaling 1 (SOCS1) is an important negative regulator for cytokines; however, the role of SOCS1 in Th17 differentiation has not been clarified. We generated T cell-specific SOCS1-deficient mice and found that these mice were extremely resistant to a Th17-dependent autoimmune disease model, experimental autoimmune encephalomyelitis. SOCS1-deficient naive CD4(+) T cells were predominantly differentiated into Th1 and poorly into Th17 in vitro. These phenotypes were canceled in IFN-gamma(-/-) background, suggesting that a large amount of IFN-gamma in SOCS1-deficient T cells suppressed Th17 differentiation. IL-6 plus TGF-beta enhanced retinoic acid receptor-related orphan receptor (ROR)-gammat expression and suppressed IFN-gamma production in wild-type T cells, whereas these effects were severely impaired in SOCS1-deficient T cells. These phenotypes can be partly explained by STAT3 suppression by enhanced SOCS3 induction through hyper-STAT1 activation in SOCS1-deficient T cells. In addition, SOCS1-deficient T cells were much less sensitive to TGF-beta. Suppression of Th1 differentiation by TGF-beta was impaired in SOCS1-deficient T cells. TGF-beta-mediated Smad transcriptional activity was severely inhibited in SOCS1-deficient cells in the presence of IFN-gamma. Such impairment of TGF-beta functions were not observed in SOCS3-overexpressed cells, indicating that suppression of Smads was independent of SOCS3. Therefore, SOCS1 is necessary for Th17 differentiation by suppressing antagonistic effect of IFN-gamma on both STAT3 and Smads. Induction of SOCS3 can partly explain IFN-gamma-mediated STAT3 suppression, while other mechanism(s) will be involved in IFN-gamma-mediated Smad suppression. SOCS1-deficient T cells will be very useful to investigate the molecular mechanism for the STAT1-mediated suppression of Th17 development.. |
| 85. |
Hiroyuki Mori, Takashi Shichita, Qingsheng Yu, Ryoko Yoshida, Masayuki Hashimoto, Fuyuki Okamoto, Takahiro Torisu, Mako Nakaya, Takashi Kobayashi, Giichi Takaesu, Akihiko Yoshimura, Suppression of SOCS3 expression in the pancreatic β-cell leads to resistance to type 1 diabetes, Biochemical and Biophysical Research Communications, 10.1016/j.bbrc.2007.05.198, 359, 4, 952-958, 2007.08, Type 1 diabetes results from the selective destruction of insulin-producing pancreatic β-cells during islet inflammation, which involves inflammatory cytokines and free radicals. However, mechanisms for protecting β-cells from destruction have not been clarified. In this study, we define the role of SOCS3 on β-cell destruction using β-cell-specific SOCS3-conditional knockout (cKO) mice. The β-cell-specific SOCS3-deficient mice were resistant to the development of diabetes caused by streptozotocin (STZ), a genotoxic methylating agent, which has been used to trigger β-cell destruction. The islets from cKO mice demonstrated hyperactivation of STAT3 and higher induction of Bcl-xL than did islets from WT mice, and SOCS3-deficient β-cells were more resistant to apoptosis induced by STZ in vitro than were WT β-cells. These results suggest that enhanced STAT3 signaling protects β-cells from destruction induced by a genotoxic stress and that STAT3/SOCS3 can be a potential therapeutic target for the treatment of type 1 diabetes.. |
| 86. |
Daigo Yoshiga, Naoichi Sato, takehiro torisu, Hiroyuki Mori, Ryoko Yoshida, Seiji Nakamura, Giichi Takaesu, Takashi Kobayashi, Akihiko Yoshimura, Adaptor protein SH2-B linking receptor-tyrosine kinase and Akt promotes adipocyte differentiation by regulating peroxisome proliferator-activated receptor γ messenger ribonucleic acid levels, Molecular Endocrinology, 10.1210/me.2006-0413, 21, 5, 1120-1131, 2007.05. |
| 87. |
Daigo Yoshiga, Naoichi Sato, Takehiro Torisu, Hiroyuki Mori, Ryoko Yoshida, Seiji Nakamura, Giichi Takaesu, Takashi Kobayashi, Akihiko Yoshimura, Adaptor protein SH2-B linking receptor-tyrosine kinase and Akt promotes adipocyte differentiation by regulating peroxisome proliferator-activated receptor gamma messenger ribonucleic acid levels., Molecular endocrinology (Baltimore, Md.), 21, 5, 1120-31, 2007.05, Adipocyte differentiation is regulated by insulin and IGF-I, which transmit signals by activating their receptor tyrosine kinase. SH2-B is an adaptor protein containing pleckstrin homology and Src homology 2 (SH2) domains that have been implicated in insulin and IGF-I receptor signaling. In this study, we found a strong link between SH2-B levels and adipogenesis. The fat mass and expression of adipogenic genes including peroxisome proliferator-activated receptor gamma (PPARgamma) were reduced in white adipose tissue of SH2-B-/- mice. Reduced adipocyte differentiation of SH2-B-deficient mouse embryonic fibroblasts (MEFs) was observed in response to insulin and dexamethasone, whereas retroviral SH2-B overexpression enhanced differentiation of 3T3-L1 preadipocytes to adipocytes. SH2-B overexpression enhanced mRNA level of PPARgamma in 3T3-L1 cells, whereas PPARgamma levels were reduced in SH2-B-deficient MEFs in response to insulin. SH2-B-mediated up-regulation of PPARgamma mRNA was blocked by a phosphatidylinositol 3-kinase inhibitor, but not by a MAPK kinase inhibitor. Insulin-induced Akt activation and the phosphorylation of forkhead transcription factor (FKHR/Foxo1), a negative regulator of PPARgamma transcription, were up-regulated by SH2-B overexpression, but reduced in SH2-B-deficient MEFs. These data indicate that SH2-B is a key regulator of adipogenesis both in vivo and in vitro by regulating the insulin/IGF-I receptor-Akt-Foxo1-PPARgamma pathway.. |
| 88. |
Takehiro Torisu, Naoichi Sato, Daigo Yoshiga, Takashi Kobayashi, Tomoko Yoshioka, Hiroyuki Mori, Mitsuo Iida, Akihiko Yoshimura, The dual function of hepatic SOCS3 in insulin resistance in vivo, Genes to Cells, 10.1111/j.1365-2443.2007.01044.x, 12, 2, 143-154, 2007.02, Inflammation associates with insulin resistance, which dysregulates nutrient homeostasis and leads to diabetes. The suppressor of cytokine signaling 3 (SOCS3), which is induced by pro-inflammatory cytokines, such as TNFα and IL-6, has been implicated in inflammation-mediated insulin resistance in the liver and adipocytes. However, no genetic evidence has been provided for the involvement of SOCS3 on insulin resistance. Here, we generated hepatocyte-specific SOCS3-deficient (L-SOCS3 cKO) mice and examined insulin sensitivity. Being consistent with a previous idea, the loss of SOCS3 in the liver apparently improved insulin sensitivity. However, unexpectedly, L-SOCS3 cKO mice exhibited obesity and systemic insulin resistance with age. Insulin signaling was rather suppressed in muscles, suggesting that deletion of the SOCS3 gene in the liver modulates insulin sensitivity in other organs. Anti-inflammatory reagent, sodium salicylate, partial improved insulin resistance of aged L-SOCS3 cKO mice, suggesting that enhanced inflammatory status is associated with the phenotype of these mice. STAT3 was hyperactivated and acute-phase proteins were elevated in L-SOCS3 cKO mice liver, which were reduced by sodium salicylate treatment. We conclude that hepatic SOCS3 is a mediator of insulin resistance in the liver; however, lack of SOCS3 in the liver promotes systemic insulin resistance by mimicking chronic inflammation.. |
| 89. |
Hiroyuki Mori, Reiko Hanada, Toshikatsu Hanada, Daisuke Aki, Ryuichi Mashima, Hitomi Nishinakamura, Takehiro Torisu, Kenneth R. Chien, Hideo Yasukawa, Akihiko Yoshimura, Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity, Nature medicine, 10.1038/nm1071, 10, 7, 739-743, 2004.07, Leptin is an adipocyte-derived hormone that plays a key role in energy homeostasis, yet resistance to leptin is a feature of most cases of obesity in humans and rodents. In vitro analysis suggested that the suppressor of cytokine signaling-3 (Socs3) is a negative-feedback regulator of leptin signaling involved in leptin resistance. To determine the functional significance of Socs3 in vivo, we generated neural cell-specific SOCS3 conditional knockout mice using the Cre-IoxP system. Compared to their wild-type littermates, Socs3-deficient mice showed enhanced leptin-induced hypothalamic Stat3 tyrosine phosphorylation as well as pro-opiomelanocortin (POMC) induction, and this resulted in a greater body weight loss and suppression of food intake. Moreover, the Socs3-deficient mice were resistant to high fat diet-induced weight gain and hyperleptinemia, and insulin-sensitivity was retained. These data indicate that Socs3 is a key regulator of diet-induced leptin as well as insulin resistance. Our study demonstrates the negative regulatory role of Socs3 in leptin signaling in vivo, and thus suppression of Socs3 in the brain is a potential therapy for leptin-resistance in obesity.. |
| 90. |
Takahiro Torisu, Motohiro Esaki, Takayuki Matsumoto, Shotaro Nakamura, Koichi Azuma, Mitsuo Okada, Hiroshi Tsuji, Takashi Yao, Mitsuo Iida, A rare case of ulcerative colitis complicating Wilson's disease
Possible association between the two diseases, Journal of Clinical Gastroenterology, 10.1097/00004836-200207000-00010, 35, 1, 43-45, 2002.07, A case of ulcerative colitis complicated by Wilson's disease is described. In this case, ulcerative colitis occurred 12 years after the diagnosis of Wilson's disease, and the colitis was intractable to prednisolone and salazosulfapyridine. Because copper is one of the trace elements necessary for antioxidant defenses during inflammatory process, altered copper metabolism may have contributed to the intractability of the ulcerative colitis in this case.. |
