Faculty Profiles - akihide Tanimoto

Ke-Yong Wang, Akihide Tanimoto, Yasuyuki Sasaguri . Role of histamine in atherosclerotic lesions . Journal of UOEH32 ( 1 ) 63 - 71 2010Reviewed

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：University of Occupational and Environmental Health

Histamine is synthesized from L-histidine by histidine decarboxylase and is involved in a variety of physiologic responses, such as inflammation, type I allergy, gastric acid secretion and neurotransmission. In the arteriosclerotic lesions, histamine produced by macrophage-derived foam cells acts on smooth muscle cells, endocrine cells and inflammation cells through the specific histamine receptors and regulates the expression of many molecules concerned with inflammatory reaction. A regulatory system of chronic inflammatory reaction by the histamine network is involved in the formation and development of arteriosclerosis.

DOI： 10.7888/juoeh.32.63

Scopus

王克よう, 谷本昭英, 稲永隆, 山田壮亮, 島尻正平, 丁妍, 郭きん, 笹栗靖之 . 大動脈弁狭窄症による慢性心不全患者にみられた肺毛細血管腫症の1剖検例(Pulmonary Capillary Hemangiomatosis In Chronic Cardiac Failure due to Aortic Stenosis) . 産業医科大学雑誌31 ( 4 ) 339 - 344 2009.12Reviewed

Language：English Publishing type：Research paper (scientific journal) Publisher：産業医科大学

我々は大動脈弁狭窄症を伴った肺毛細血管腫症の1剖検例を経験したので報告する。症例は86歳日本人女性、大動脈弁狭窄症による慢性心不全にて血液透析を施行中に、突然死となった。剖検すると、大動脈弁の高度な狭窄と、両心室壁の肥厚を伴った高度な心肥大とが認められた。肺の病理組織学的所見では、ヘモジデリンを貪食した肺胞内マクロファージの集簇を伴って、肥厚した肺胞壁における毛細血管のびまん性増生が認められ、肺毛細血管腫症に一致する像であった。以上より当症例は、大動脈弁狭窄症により長期間慢性的に持続した肺うっ血が、肺毛細血管腫症を引き起こしたものと考えられた。(著者抄録)

DOI： 10.7888/juoeh.31.339

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2009&ichushi_jid=J00526&link_issn=&doc_id=20091209060003&doc_link_id=%2Fdc5juoeh%2F2009%2F003104%2F003%2F0339-0344%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdc5juoeh%2F2009%2F003104%2F003%2F0339-0344%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

大井恭代, 雷哲明, 久木田妙子, 相良安昭, 相良吉昭, 馬場信一, 玉田修吾, 松山義人, 佐々木道朗, 土持進作, 安藤充嶽, 相良吉厚, 吉田愛知, 梅北善久, 谷本昭英 . 非触知乳癌の臨床病理学的特徴 . 乳癌の臨床24 ( 6 ) 762 - 763 2009.12Reviewed

Language：Japanese Publisher：(株)篠原出版新社

2003年5月〜2008年12月に根治手術を施行した非触知乳癌330例(全乳癌の12.6%)を対象に臨床病理学的特徴を検討した。MMG石灰化症例120例の確定診断は、生検組織診が77例、穿刺吸引細胞診が43例で、comedo typeでは穿刺吸引細胞診が有用であった。また、ステレオガイド下切除生検から低侵襲のマンモトーム吸引式針生検への移行がみられ、症例数は増加傾向であった。MMG/US mass症例127例は、非浸潤癌あるいは浸潤径の小さな浸潤癌が92例で、穿刺吸引細胞診は122例に施行され、不適率は4.1%、91.5%を悪性もしくは悪性疑いと診断しえた。鑑別困難例が7.7%あり、すべて低異型度癌であった。US massのみの症例86例の病理学的特徴は、MMG/US massとほぼ同様であった。乳頭分泌を発現契機とする症例43例は、23例がneuroendocrine differentiationを示し、同時期の非浸潤性乳管癌全体と比較して有意に高い傾向であった。pT2以上の症例は、3例が乳頭腺管癌、2例が浸潤性小葉癌であった。浸潤性小葉癌は穿刺吸引細胞診においてごく少数の小型異型細胞を認めるのみであった。非触知乳癌は画像所見や症状により病理学的特徴を有しており、それらを考慮することで、診断効率・精度の向上が期待できると思われた。

Sohsuke Yamada, Akihide Tanimoto, Ke-Yong Wang, Shohei Shimajiri, Yasuyuki Sasaguri . Stromal luteoma and nodular hyperthecosis of the bilateral ovaries associated with atypical endometrial hyperplasia of the uterus . PATHOLOGY INTERNATIONAL59 ( 11 ) 831 - 833 2009.11Reviewed International journal

Sohsuke Yamada, Akihide Tanimoto, Yasumasa Matsuki, Yuji Hisada, Yasuyuki Sasaguri . Sclerosing encapsulating peritonitis (abdominal cocoon) associated with liver cirrhosis and diffuse large B-cell lymphoma: Autopsy case . PATHOLOGY INTERNATIONAL59 ( 9 ) 681 - 686 2009.9Reviewed International journal

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

A case of sclerosing encapsulating peritonitis (SEP) associated with liver cirrhosis (LC) and complicated by diffuse large B-cell lymphoma (DLBCL) is reported herein. A 49-year-old Japanese man had undergone peritoneo-venous shunt against refractory ascites due to hepatitis C virus-positive uncompensated LC for 2 years. After he received a diagnosis of DLBCL of the left neck lymph node 3 months before his death, palliative care was given because of his poor general condition. He developed severe abdominal distention and pain over 1 week and was found to have marked ascites and whole bowel lumped together on abdominal CT. At autopsy, the peritoneum was covered with a thick white membrane and the bowel could not be distinguished, which was macroscopically characterized by a cocoon-like appearance. Histology indicated a proliferation of diffusely thickened or hyalinized fibrocollagenous tissue in the entire peritoneum with a slight chronic inflammatory infiltrate and without remarkable change of mucosa. A diagnosis of SEP, also known as abdominal cocoon, was established based on these features. Additionally, in the abdominal cavity, a large amount of serous ascites and multiple peritoneal nodules or masses involved by DLBCL were recognized. To the authors' knowledge this is the first case report of SEP associated with LC and complicated by the invasion of DLBCL in the abdominal cavity.

DOI： 10.1111/j.1440-1827.2009.02427.x

林海輝, 成田竜一, 日浦政明, 阿部慎太郎, 田原章成, 原田大, 谷本昭英, 笹栗靖之 . Giant cell hepatitisの組織像を呈した自己免疫性肝炎の1例 . 臨牀と研究86 ( 7 ) 945 - 946 2009.7

石原善三郎, 大西英生, 戸羽直樹, 中村利孝, 青木隆敏, 谷本昭英 . 脛骨骨幹端から骨端に進展したBrodie骨膿瘍の1例 . 整形・災害外科52 ( 7 ) 923 - 927 2009.6

Publisher：金原出版(株)

17歳男。2年前に誘因なく右足関節痛が出現し、前医でのX線で骨嚢胞性疾患を指摘されたが、疼痛が消失したため放置していた。今回、再び疼痛が出現し、MRIで内部がT1強調像で低信号、T2強調像で高信号を示す嚢胞性病変を認め、特に病変部に4層構造(病巣中心のT1強調像での低信号域、病巣内壁のT1強調像でのリング状高信号域、病巣外壁のT2強調像でのリング状低信号域、病巣外壁周辺のT1強調像での低信号域)を認めた。また、CTの矢状断像で骨幹端部から骨端軟骨下骨まで進展した病巣を認め、横断像で病巣部のfistulaを認めた。Brodie骨腫瘍と診断し、病巣の掻爬および洗浄術を施行し、術後はセフェム系抗生剤を3ヵ月間経口投与した。経過は良好で、術後2年2ヵ月経過した現在、再発は認めていない。

Masaki Shiota, Hiroto Izumi, Akihide Tanimoto, Mayu Takahashi, Naoya Miyamoto, Eiji Kashiwagi, Akihiko Kidani, Gen Hirano, Daisuke Masubuchi, Yasushi Fukunaka, Yoshihiro Yasuniwa, Seiji Naito, Shigeru Nishizawa, Yasuyuki Sasaguri, Kimitoshi Kohno . Programmed Cell Death Protein 4 Down-regulates Y-Box Binding Protein-1 Expression via a Direct Interaction with Twist1 to Suppress Cancer Cell Growth . CANCER RESEARCH69 ( 7 ) 3148 - 3156 2009.4Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER ASSOC CANCER RESEARCH

Programmed cell death protein 4 (PDCD4) has recently been shown to be involved in both transcription and translation, and to regulate cell growth. However, the mechanisms underlying PDCD4 function are not well understood. In this study, we show that PDCD4 interacts directly with the transcription factor Twist1 and leads to reduced cell growth through the down-regulation of the Twist1 target gene Y-box binding protein-1 (YB-1). PDCD4 interacts with the DNA binding domain of Twist1, inhibiting its DNA binding ability and YB-1 expression. Immunohistochemical analysis showed that an inverse correlation between nuclear PDCD4 and YB-1 expression levels was observed in 37 clinical prostate cancer specimens. Growth suppression by PDCD4 expression was completely recovered by either Twist1 or YB-1 expression. Moreover, PDCD4-overexpressing cells are sensitive to cisplatin and paclitaxel but not to etoposide or 5-fluorouracil. In summary, PDCD4 negatively regulates YB-1 expression via its interaction with Twist1 and is involved in cancer cell growth and chemoresistance. [Cancer Res 2009;69(7):3148-56]

DOI： 10.1158/0008-5472.CAN-08-2334

山田壮亮, 谷本昭英, 島尻正平, 笹栗靖之 . 皮膚腫瘍papillary eccrine adenomaの1症例 . 診断病理26 ( 1 ) 58 - 61 2009.1

Publisher：(一社)日本病理学会

79歳男性の皮膚に発生したpapillary eccrine adenoma(PEA)の1例を経験したので報告する。右大腿部皮膚に軽い掻痒感を伴う腫瘤を自覚し、切除術を施行された。肉眼的に、径16×10×8mmで、黄白色調の境界明瞭な真皮内腫瘍であった。組織学的に、腫瘍はほぼ対称性の真皮中層から下層の病変で、拡張した腺管や嚢胞により構成されており、好酸性無構造物質の貯留を伴っていた。管腔の多くは異型のない二層性上皮で裏打ちされており、腔内へ乳頭状に突出する像や篩状様構造を呈していた。鑑別としてtubular apocrine adenoma(TAA)とaggressive digital papillary adenocarcinoma(ADPAca)が挙げられたが、前者は明らかな断頭分泌像を認めないことより、後者は細胞異型、構造異型の乏しいことより、PEAと診断した。(著者抄録)

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2009&ichushi_jid=J03623&link_issn=&doc_id=20090227260014&doc_link_id=%2Fcd9jjodp%2F2009%2F002601%2F014%2F0058-0061%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcd9jjodp%2F2009%2F002601%2F014%2F0058-0061%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Shiota M, Izumi H, Tanimoto A, Takahashi M, Miyamoto N, Kashiwagi E, Kidani A, Hirano G, Masubuchi D, Fukunaka Y, Yasuniwa Y, Naito S, Nishizawa S, Sasaguri Y, Kohno K. . Programmed cell death protein 4 down-regulates Y-box binding protein-1 expression via a direct interaction with Twist1 to suppress cancer cell growth. . Cancer Res. 69 3148 - 3156 2009Reviewed

Yamada S, Tanimoto A, Matsuki Y, Hisada Y, Sasaguri Y. . Sclerosing encapsulating peritonitis (abdominal cocoon) associated with liver cirrhosis and diffuse large B-cell lymphoma: autopsy case. . Pathol Int.59 681 - 686 2009Reviewed

Yamada S, Tanimoto A, Wang KY, Shimajiri S, Sasaguri Y. . Stromal luteoma and nodular hyperthecosis of the bilateral ovaries associated with atypical endometrial hyperplasia of the uterus. . Pathol Int.59 831 - 833 2009Reviewed

Wang KY, Tanimoto A, Inenaga T, Yamada S, Shimajiri S, Ding Y, Guo X, Sasaguri Y. . Pulmonary capillary hemangiomatosis in chronic cardiac failure due to aortic stenosis. . J UOEH.31 339 - 344 2009Reviewed

小原光祥, 岡ハル子, 佐藤斉, 藤原仁, 岩井幸子, 松山篤二, 島尻正平, 久岡正典, 谷本昭英, 濱田哲夫 . 乳腺髄様癌の4症例 . 日本臨床細胞学会九州連合会雑誌39 81 - 85 2008.7

Publisher：日本臨床細胞学会-九州連合会

いずれも乳房腫瘤を主訴とし、症例1(75歳)は定型的乳房切除術、症例2(31歳)は非定型的乳房切除術、症例3(40歳)と症例4(48歳)は乳房温存術(円状部分切除)を施行され、全例が4人の病理医により髄様癌と診断された。これら4例についてRadolfiらの3群亜型分類による再評価を行い、亜型分類とそれぞれの穿刺吸引細胞所見及び予後を比較検討した。Radolfiらの亜分類によるTMC(typical medullary carcinoma)に特徴的な細胞像は未分化な腫瘍細胞としての核・細胞質所見であると考えられた。

Ken Sabanai, Masato Tsutsui, Akinori Sakai, Hideyuki Hirasawa, Shinya Tanaka, Eiichiro Nakamura, Akihide Tanimoto, Yasuyuki Sasaguri, Masako Ito, Hiroaki Shimokawa, Toshitaka Nakamura, Nobuyuki Yanagihara . Genetic disruption of all NO synthase isoforms enhances BMD and bone turnover in mice in vivo: Involvement of the renin-angiotensin system . JOURNAL OF BONE AND MINERAL RESEARCH23 ( 5 ) 633 - 643 2008.5Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER SOC BONE & MINERAL RES

Introduction: NO is synthesized by three different NO synthase (NOS) isoforms, including neuronal (nNOS), inducible (iNOS) and endothelial NOS (eNOS). The roles of NO in bone metabolism have been extensively investigated in pharmacological studies and in studies with NOS isoform-deficient mice. However, because of the nonspecificity of agents and compensation among the NOS isoforms, the ultimate roles of endogenous NO are still poorly understood. To address this point, we successfully generated mice in which all three NOS genes are completely disrupted. In this study, we examined whether bone metabolism is abnormal in those mice.
Materials and Methods: Experiments were performed in 12-wk-old male wildtype, singly nNOS(-/-), iNOS(-/-), and eNOS(-/-) and triply n/i/eNOS(-/-) mice. BMD was assessed by DXA. The kinetics of osteoblastic bone formation and those of osteoclastic bone resorption were evaluated by measurements of morphological and biochemical markers.
Results: BMD was significantly higher only in the triply NOS-/- mice but not in any singly NOS-/- mice compared with the wildtype mice. Markers of osteoblastic bone formation, including bone formation rate, mineral apposition rate, and serum alkaline phosphatase concentration, were also significantly larger only in the triply NOS-/- mice compared with wildtype mice. Furthermore, markers of osteoclastic bone resorption, including osteoclast number, osteoclast surface, and urinary deoxypyridinoline excretion, were again significantly greater only in the triply NOS-/- mice. Importantly, the renin-angiotensin system in bone was significantly activated in the triply NOS-/- mice, and long-term oral treatment with an angiotensin II type I (AT,) receptor blocker normalized this pathological bone remodeling in those mice.
Conclusions: These results provide the first direct evidence that genetic disruption of the whole NOS system enhances BMD and bone turnover in mice in vivo through the AT, receptor pathway, showing the critical role of the endogenous NO/NOS system in maintaining bone homeostasis.

DOI： 10.1359/JBMR.080107

Sohsuke Yamada, Ke-Yong Wang, Akihide Tanimoto, Jianglin Fan, Shohei Shimajiri, Shuji Kitajima, Masatoshi Morimoto, Masato Tsutsui, Teruo Watanabe, Kosei Yasumoto, Yasuyuki Sasaguri . Matrix metalloproteinase 12 accelerates the initiation of atherosclerosis and stimulates the progression of fatty streaks to fibrous plaques in transgenic rabbits . AMERICAN JOURNAL OF PATHOLOGY172 ( 5 ) 1419 - 1429 2008.5Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER SOC INVESTIGATIVE PATHOLOGY, INC

Whether fatty streaks are directly followed by fibrous plaque formation in atherosclerosis remains controversial. Disruption of the basement membrane and elastic layers is thought to be essential for this process. Matrix metalloproteinase 12 (MMP-12) can degrade a broad spectrum of substrates, but the role of MMP-12 in the early stage of atherosclerosis is unclear. To investigate MMP-12 function in the initiation and progression of atherosclerosis, we investigated macrophage migration and elastolysis in relation to fatty streaks in human MMP-12 transgenic (hMMP-12 Tg) rabbits. Fatty streaks in hMMP-12 Tg rabbits fed a 1% cholesterol diet for 6 weeks (cholesterol-induced model of atherosclerosis) were more pronounced and were associated with more significant degradation of the internal elastic layer compared with wild-type (WT) animals. Numbers of infiltrating macrophages and smooth muscle cells in the lesions were increased in hMMP-12 Tg compared with WT animals. In both cuff- and ligation-induced models of atherosclerosis, smooth muscle cell-predominant atherosclerotic lesions were elevated with significant elastolysis of the internal elastic lamina in Tg compared with WT animals; "microelastolytic sites" were recognized before formation of the neointima in the cuff model only. These results indicate that MMP-12 may be critical to the initiation and progression of atherosclerosis via degradation of the elastic layers and/or basement membrane. Therefore, a specific MMP-12 inhibitor might prove useful for the treatment of progressive atherosclerosis.

DOI： 10.2353/ajpath.2008.070604

Sei Nakata, Masato Tsutsui, Hiroaki Shimokawa, Osamu Suda, Tsuyoshi Morishita, Kiyoko Shibata, Yasuko Yatera, Ken Sabanai, Akihide Tanimoto, Machiko Nagasaki, Hiromi Tasaki, Yasuyuki Sasaguri, Yasuhide Nakashima, Yutaka Otsuji, Nobuyuki Yanagihara . Spontaneous myocardial infarction in mice lacking all nitric oxide synthase isoforms . CIRCULATION117 ( 17 ) 2211 - 2223 2008.4Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Background - The roles of nitric oxide (NO) in the cardiovascular system have been investigated extensively in pharmacological studies with NO synthase (NOS) inhibitors and in studies with NOS isoform - deficient mice. However, because of the nonspecificity of the NOS inhibitors and the compensatory interactions among NOS isoforms (nNOS, iNOS, and eNOS), the ultimate roles of endogenous NO derived from the entire NOS system are still poorly understood. In this study, we examined this point in mice deficient in all 3 NOS isoforms (triply n/i/eNOS(-/-) mice) that we have recently developed.
Methods and Results - The triply n/i/eNOS(-/-) mice, but not singly eNOS(-/-) mice, exhibited markedly reduced survival, possibly due to spontaneous myocardial infarction accompanied by severe coronary arteriosclerotic lesions. Furthermore, the triply n/i/eNOS(-/-) mice manifested phenotypes that resembled metabolic syndrome in humans, including visceral obesity, hypertension, hypertriglyceridemia, and impaired glucose tolerance. Importantly, activation of the renin-angiotensin system was noted in the triply n/i/eNOS(-/-) mice, and long-term oral treatment with an angiotensin II type 1 receptor blocker significantly suppressed coronary arteriosclerotic lesion formation and the occurrence of spontaneous myocardial infarction and improved the prognosis of those mice, along with ameliorating the metabolic abnormalities.
Conclusions - These results provide the first direct evidence that genetic disruption of the whole NOS system causes spontaneous myocardial infarction associated with multiple cardiovascular risk factors of metabolic origin in mice in vivo through the angiotensin II type 1 receptor pathway, demonstrating the critical role of the endogenous NOS system in maintaining cardiovascular and metabolic homeostasis.

DOI： 10.1161/CIRCULATIONAHA.107.742692