Papers - MIHARA Hiroshi

潰瘍性大腸炎における発がんリスクマーカーとしてのmiR-124aのDNAメチル化異常

板谷 優子, 安藤 孝将, 南條 宗八, 吉田 啓紀, 植田 亮, 三原 弘, 藤浪 斗, 梶浦 新也, 西川 潤, 細川 歩, 杉山 敏郎

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  110 ( 臨増総会 ) A224 - A224  2013.02

HER2陽性進行胃癌に対するTrastuzumabの使用経験

植田 亮, 細川 歩, 吉田 啓紀, 南條 宗八, 三原 弘, 安藤 孝将, 梶浦 新也, 藤浪 斗, 西川 潤, 小川 浩平, 杉山 敏郎

日本胃癌学会総会記事 ( (一社)日本胃癌学会 )  85回   335 - 335  2013.02

腹水を有する進行・再発胃癌の化学療法における血清CA125早期低下の意義

安藤 孝将, 細川 歩, 板谷 優子, 吉田 啓紀, 植田 亮, 三原 弘, 藤浪 斗, 梶浦 新也, 西川 潤, 小林 隆司, 堀川 直樹, 薮下 和久, 野手 雅幸, 杉山 敏郎

日本胃癌学会総会記事 ( (一社)日本胃癌学会 )  85回   273 - 273  2013.02

HER2陽性進行胃癌に対するTrastuzumabの使用経験

植田 亮, 細川 歩, 禿 晃仁, 高木 宏明, 吉田 啓紀, 齋藤 聖子, 三原 弘, 安藤 孝将, 藤浪 斗, 梶浦 新也, 西川 潤, 小川 浩平, 杉山 敏郎

日本癌治療学会誌 ( (一社)日本癌治療学会 )  47 ( 3 ) 2209 - 2209  2012.10

Fragmented CagA Protein is Highly Immunoreactive in Japanese Patients

Kazuki Yamada, Toshiro Sugiyama, Hiroshi Mihara, Shinya Kajiura, Seiko Saito, Yuko Itaya, Hidemoto Yamawaki, Takayuki Ando, Takahiko Kudo, Ayumu Hosokawa, Masumi Okuda, Kenichi Fukunaga, Junko K. Akada, Teruko Nakazawa

HELICOBACTER ( WILEY-BLACKWELL )  17 ( 3 ) 187 - 192  2012.06  [Refereed]

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Background: High-molecular-weight cell-associated proteins (HM-CAP) assay is the most popular serological immunoassay worldwide and has been developed from US isolates as the antigens. The accuracy is reduced when the sera are from adults and children in East Asia including Japan. To overcome the reduced accuracy, an enzyme immunoassay using Japanese strainderived HM-CAP (JHM-CAP) was developed, in which the antigens were prepared by exactly the same procedure as HM-CAP. The performance of JHM-CAP was better than that of HM-CAP in Japanese adults as well as in children. The higher sensitivity was because of the presence of 100-kDa protein that was absent in the preparation of HM-CAP antigen. Materials and Methods: Immunoblot analysis and peptide mass fingerprinting methods were used to identify the distinctive 100-kDa protein present in JHM-CAP antigens. The peptide sequence and identification were analyzed by Mascot Search on the database of Helicobacter pylori. The identified protein was confirmed by immunoblot with a specific antibody and inhibition assay by the sera. Results: The distinctive 100-kDa protein was a fragment of CagA derived from Japanese clinical isolates, and the sera of Japanese patients had strongly reacted to the protein, probably to the exposed epitope on the fragmented CagA. The fragmentation of CagA had occurred in the process of antigen preparation in Japanese isolates, not in US isolates even under the same preparation. Conclusion: The distinctive 100-kDa protein was a fragment of CagA protein of H. pylori derived from Japanese clinical isolates, and Japanese patients including children are likely to react strongly to the exposed epitopes on fragmented CagA.

DOI PubMed

最近10年間における出血性胃・十二指腸潰瘍の経年的変化

藤浪 斗, 細川 歩, 小川 浩平, 西川 潤, 梶浦 新也, 安藤 孝将, 三原 弘, 植田 亮, 吉田 啓紀, 杉山 敏郎

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  28 ( 1 ) 78 - 78  2012.05

Endoscopic hemostasis attempt during intra-aortic balloon occlusion for massively bleeding duodenal ulcer. A case report

Masaaki Yamada, Keizo Kato, Rei Kashima, Makoto Fujimoto, Hiroshi Mihara, Shinya Kajiura, Haruka Fujinami, Michio Tanaka

Endoscopic Forum for Digestive Disease   28 ( 1 ) 35 - 41  2012.05

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A 71-year-old man was admitted in an unconscious state with bloody stools. By endoscopy we detected a large amount of blood in the duodenal bulb and a portion of an ulcer lesion on the posterior wall. We were unable to locate the bleeding vessel because of duodenal deformity and massive hemorrhage. Despite blood transfusion, the patient's state continued to deteriorate. His blood pressure was below 80 mm Hg. To treat the shock, we inserted the intra-aortic balloon occlusion (IABO) catheter, which maintained the blood pressure of the upper half of the body and lessened gastrointestinal bleeding. We then attempted endoscopic hemostasis without success. We were able to transfer the patient to the operation room with while maintaining the blood pressure. The operative findings indicated penetration of the duodenal ulcer into the pancreas and stiff adhesion with the peritoneum. Oozing was observed at several locations of the ulcer floor (pancreas itself) and the gastro-duodenal artery had ruptured at 2 sites. The JSGE guideline for the management of peptic ulcer recommends interventional radiology and surgery in cases where endoscopic hemostasis is difficult. However, in patients exhibiting hemodynamic instability with critically uncontrollable hemorrhagic shock, IABO can be effective in maintaining blood pressure and transferring patients safely.

出血性十二指腸潰瘍によるショック離脱困難例に対する、内視鏡的止血術と大動脈閉塞バルーン(IABO)挿入法併用の1例

山田 正明, 加藤 慶三, 鹿島 励, 藤本 誠, 三原 弘, 梶浦 新也, 藤浪 斗, 田中 三千雄

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  28 ( 1 ) 35 - 41  2012.05

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外傷や産科関連の疾患による出血などの腹部救急領域において、出血性ショック時の治療の一環として大動脈閉塞バルーン(intra-aortic balloon occlusion、IABO)が頻用されている。今回、出血性十二指腸潰瘍によってショックから離脱できなかった症例に対し、IABO挿入法を併用した内視鏡的止血術を施行した。内視鏡止血術では止血に至らなかったが、IABOによる下行大動脈遮断によって、上半身の血圧維持が可能となり、緊急外科手術のための手術室への移送が可能となった。従来、消化管出血に対する内視鏡的止血術が困難な例には外科手術、IVRが適応とされてきた。しかし、その様な治療を行う場所への移送も困難な程に高度なショック状態にある症例に対しては、IABO挿入法の併用は移送を可能にし、有用な手段であると考えられた。(著者抄録)

[The 38th Hokuriku Branch Seminar Report: overview and evaluation results of the first abdominal emergency medical training course (AbdEMeT)].

Mihara H, Okazawa S, Wada A, Murakami J, Sugiyama T, Nomura H, Kajinami K

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   101 ( 4 ) 1112 - 1116  2012.04  [Refereed]  [Domestic journal]

PubMed

Two cases of thiopurine-induced acute pancreatitis in inflammatory bowel disease

Jun Nishikawa, Takahiko Kudo, Takako Miyazaki, Hiroshi Mihara, Akira Ueda, Takayuki Ando, Shinya Kajiura, Haruka Fujinami, Kohei Ogawa, Ayumu Hosokawa, Toshiro Sugiyama

Journal of Japanese Society of Gastroenterology   109 ( 2 ) 224 - 230  2012.02  [Refereed]

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Thiopurine drugs have been widely used in the treatment of inflammatory bowel disease. However, their use is limited by adverse effect that can lead to cessation of therapy. We report 2 cases of thiopurine-induced acute pancreatitis in patients with inflammatory bowel disease. Both patients complained of abdominal pain, showed elevated pancreatic enzymes, and swollen pancreases on computed tomography. The patients' signs and symptoms resolved uneventfully after withdrawal of the thiopurine drugs. Although the mechanism of thiopurine-induced pancreatitis remains unclear, close monitoring and early recognition of acute pancreatitis is important in the management of new thiopurine users.

DOI PubMed

悪性リンパ腫診断における血清可溶性インターロイキン-2受容体値の再検討

村上 純, 三原 弘, 在田 幸太郎, 和田 暁法, 宮園 卓宜, 杉山 敏郎

日本内科学会雑誌 ( (一社)日本内科学会 )  101 ( Suppl. ) 257 - 257  2012.02

Irinotecan Plus Mitomycin C as Second-Line Chemotherapy for Advanced Gastric Cancer Resistant to Fluoropyrimidine and Cisplatin: A Retrospective Study

Kohei Ogawa, Ayumu Hosokawa, Akira Ueda, Seiko Saito, Hiroshi Mihara, Takayuki Ando, Shinya Kajiura, Mitsuhiro Terada, Yuji Tsukioka, Naoki Horikawa, Takashi Kobayashi, Masayuki Note, Kunihiro Sawasaki, Junya Fukuoka, Toshiro Sugiyama

GASTROENTEROLOGY RESEARCH AND PRACTICE ( HINDAWI PUBLISHING CORPORATION )  2012   640401  2012  [Refereed]

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Background. S-1 plus cisplatin has been established to be standard first-line chemotherapy for advanced gastric cancer in Japan. The optimal second-line treatment refractory to S-1 plus cisplatin remains unclear. Methods. We retrospectively studied the efficacy, toxicity, and survival of irinotecan plus mitomycin C in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin. Results. Twenty-four patients were studied. Prior chemotherapy was S-1 plus cisplatin in 15 patients, S-1 plus cisplatin and docetaxel in 8, and 5-fluorouracil plus cisplatin with radiotherapy in 1. The overall response rate was 17.4%. The median overall survival was 8.6 months, and the median progression-free survival was 3.6 months. Grade 3 or 4 toxicities included leukopenia (33%), neutropenia (50%), anemia (33%), thrombocytopenia (4%), anorexia (13%), diarrhea (4%), and febrile neutropenia (13%). Conclusion. A combination of irinotecan and mitomycin C is potentially effective in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin.

DOI PubMed

集学的内視鏡検査が、止血に役立った小腸血管異形成の一例

三原 弘, 菅谷 彰, 植田 亮, 安藤 孝将, 西川 潤, 藤浪 斗, 梶浦 新也, 小川 浩平, 細川 歩, 魚谷 英之, 杉山 敏郎

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  27 ( 2 ) 174 - 174  2011.11

Infliximab-induced lupus erythematosus in a case of ulcerative colitis

Jun Nishikawa, Takako Miyazaki, Nobuhiro Suzuki, Yuko Itaya, Hidemoto Yamawaki, Hiroshi Mihara, Yushi Hasumoto, Haruka Fujinami, Kohei Ogawa, Ayumu Hosokawa, Takahiko Kudo, Toshiro Sugiyama

Journal of Japanese Society of Gastroenterology   108 ( 9 ) 1535 - 1539  2011.09  [Refereed]

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Infliximab is widely used in the treatment of inflammatory bowel disease, but despite its good clinical efficacy and tolerance, drug-induced autoimmune disorders have been reported as adverse reactions and are a matter of concern. Here we report a patient with ulcerative colitis who developed drug-induced lupus erythematosus after infliximab treatment While this is a rare complication of infliximab, early diagnosis and successful management are essential.

DOI PubMed

進行・再発胃癌の化学療法における血清CA125の有用性

板谷 優子, 安藤 孝将, 細川 歩, 中田 直克, 鈴木 庸弘, 植田 亮, 山脇 秀元, 齋藤 聖子, 三原 弘, 蓮本 祐史, 藤浪 斗, 梶浦 新也, 西川 潤, 宮嵜 孝子, 小川 浩平, 杉山 敏郎

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  108 ( 臨増大会 ) A808 - A808  2011.09

抗血小板薬・抗凝固薬服用例の出血性胃十二指腸潰瘍に対する最適な止血術の検討

藤浪 斗, 細川 歩, 小川 浩平, 宮嵜 孝子, 西川 潤, 梶浦 新也, 蓮本 祐史, 安藤 孝将, 三原 弘, 板谷 優子, 植田 亮, 山脇 秀元, 鈴木 庸弘, 中田 直克, 杉山 敏郎

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 )  53 ( Suppl.2 ) 2793 - 2793  2011.09

Transient receptor potential vanilloid 4 (TRPV4)-dependent calcium influx and ATP release in mouse oesophageal keratinocytes

Hiroshi Mihara, Ammar Boudaka, Toshiro Sugiyama, Yoshinori Moriyama, Makoto Tominaga

JOURNAL OF PHYSIOLOGY-LONDON ( WILEY-BLACKWELL )  589 ( 14 ) 3471 - 3482  2011.07  [Refereed]

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Gastro-oesophageal reflux disease (GERD) is amulti-factorial disease that may involve oesophageal hypersensitivity to mechanical or heat stimulus as well as acids. Intraganglionic laminar endings (IGLEs) are the most prominent terminal structures of oesophageal vagal mechanosensitive afferents and may modulate mechanotransduction via purinergic receptors. Transient receptor potential channel vanilloid 4 (TRPV4) can detect various stimuli such as warm temperature, stretch and some chemicals, including 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD) and GSK1016790A. TRPV4 is expressed in many tissues, including renal epithelium, skin keratinocytes and urinary bladder epithelium, but its expression and function in the oesophagus is poorly understood. Here, we show anatomical and functional TRPV4 expression in mouse oesophagus and its involvement in ATP release. TRPV4 mRNA and protein were detected in oesophageal keratinocytes. Several known TRPV4 activators (chemicals, heat and stretch stimulus) increased cytosolic Ca(2+) concentrations in cultured WT keratinocytes but not in TRPV4 knockout (KO) cells. Moreover, the TRPV4 agonist GSK1016790A and heat stimulus evoked TRPV4-like current responses in isolated WT keratinocytes, but not in TRPV4KO cells. GSK1016790A and heat stimulus also significantly increased ATP release from WT oesophageal keratinocytes compared to TRPV4KO cells. The vesicle-trafficking inhibitor brefeldin A (BFA) inhibited the ATP release. This ATP release could be mediated by the newly identified vesicle ATP transporter, VNUT, which is expressed by oesophageal keratinocytes at the mRNA and protein levels. In conclusion, in response to heat, chemical and possibly mechanical stimuli, TRPV4 contributes to ATP release in the oesophagus. Thus, TRPV4 could be involved in oesophageal mechano -and heat hypersensitivity.

DOI PubMed

Involvement of TRPV2 Activation in Intestinal Movement through Nitric Oxide Production in Mice

Hiroshi Mihara, Ammar Boudaka, Koji Shibasaki, Akihiro Yamanaka, Toshiro Sugiyama, Makoto Tominaga

JOURNAL OF NEUROSCIENCE ( SOC NEUROSCIENCE )  30 ( 49 ) 16536 - 16544  2010.12  [Refereed]

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Transient receptor potential channel vanilloid 2 (TRPV2) can detect various stimuli such as temperature (>52 degrees C), stretch, and chemicals, including 2-aminoethoxydiphenyl borate, probenecid, and lysophospholipids. Although expressed in many tissues, including sensory and motor neurons, TRPV2 expression and function in the gastrointestinal tract is poorly understood. Here, we show TRPV2 expression in the murine intestine and its involvement in intestinal function. Almost all mouse intestinal intrinsic sensory and inhibitory motor neurons, both cell bodies and nerve fibers, showed TRPV2 immunoreactivity. Several known TRPV2 activators increased cytosolic Ca(2+) concentrations and evoked TRPV2-like current responses in dissociated myenteric neurons. Interestingly, mechanical stimuli activated inward currents in a strength-dependent manner, which were inhibited by a TRPV2 inhibitor tranilast. TRPV2 activation in isolated intestine inhibited spontaneous circular muscle contraction, which did not occur in the presence of the TRPV2 antagonist, tetrodotoxin or nitro oxide (NO) synthase pathway inhibitors. Also, increased intestinal NO production was observed in response to a TRPV2 agonist, and gastrointestinal transit in vivo was accelerated by TRPV2 agonists or an NO donor. In conclusion, TRPV2 may contribute to intestinal motility through NO production, and TRPV2 is a promising target for controlling intestinal movement.

DOI PubMed

The modified glucose clearance test: a novel non-invasive method for differentiating non-erosive reflux disease and erosive oesophagitis

H. FUJINAMI, T. KUDO, T. MIYAZAKI, A. HOSOKAWA, H. MIHARA, T. ANDO, T. SUGIYAMA

Alimentary Pharmacology & Therapeutics ( Wiley )  28 ( 10 ) 1259 - 1264  2008.11  [Refereed]

DOI

IgM-M蛋白を伴う慢性炎症性脱髄性多発神経炎の経過中に発症した小腸MALTリンパ腫

嶋 香菜子, 村上 純, 在田 幸太郎, 米澤 和美, 宮園 卓宜, 三原 弘, 折原 正周, 杉山 敏郎, 田口 芳治, 道具 伸浩, 高嶋 修太郎, 野本 一博, 石澤 伸, 高野 康雄

臨床血液 ( (一社)日本血液学会-東京事務局 )  49 ( 9 ) 1116 - 1116  2008.09