Faculty Profiles - akihide Tanimoto

保坂優斗, 盛真一郎, 馬場研二, 喜多芳昭, 又木雄弘, 上之園芳一, 内門泰斗, 前村公成, 北園育美, 谷本昭英, 新地洋之, 夏越祥次 . 盲腸軸捻転症と続発性小腸軸捻転症を発症した混合性結合組織病の1例 . 日本消化器外科学会雑誌50 ( 12 ) 1008 - 1015 2017.12盲腸軸捻転症と続発性小腸軸捻転症を発症した混合性結合組織病の1例

Publisher：(一社)日本消化器外科学会

膠原病は結合組織の障害による消化管の運動異常により,しばしば消化管病変を合併する.症例は60歳の女性で,17年前に混合性結合組織病(mixed connective tissue disease;以下,MCTDと略記)の診断を受け,以後当院膠原病内科で加療を行っていた.腹痛を主訴に来院され,盲腸軸捻転症と診断し緊急手術を施行した.回結腸動脈を軸に360°捻転していたため,捻転解除術と盲腸固定術を行った.退院後の術後37日目に腹痛を来し,腹部CTで腸管捻転の所見を認めたため,緊急手術を施行した.捻転は解除されたが広範囲の回腸の拡張を認め,減圧処置後に腸管を切除する方針とした.初回手術から51日目に再々手術を行い,拡張し蠕動低下を認めた回腸を30cm切除した.病理検査で固有筋層の萎縮を認めた.限局した固有筋層の萎縮が限局性の蠕動低下,腸管内容物の停滞を起こし,軸捻転症が発症したものと推測した.MCTDに腸管軸捻転症の合併を認めた報告例はなく,病理所見も合わせて報告する.(著者抄録)

Sohsuke Yamada, Hiroaki Kawaguchi, Tomonobu Yamada, Xin Guo, Kei Matsuo, Taiji Hamada, Naoki Miura, Takashi Tasaki, Akihide Tanimoto . Cholic Acid Enhances Visceral Adiposity, Atherosclerosis and Nonalcoholic Fatty Liver Disease in Microminipigs. . Journal of atherosclerosis and thrombosis24 ( 11 ) 1150 - 1166 2017.11Cholic Acid Enhances Visceral Adiposity, Atherosclerosis and Nonalcoholic Fatty Liver Disease in Microminipigs.Reviewed

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

AIM: We have recently established a novel swine model for studies of atherosclerosis using MicrominipigsTM (µMPs) fed a high-fat/high-cholesterol diet (HcD). Using this swine model, we re-evaluated the effects of dietary cholic acid (CA) on serum lipid profile, atherosclerosis and hepatic injuries. METHODS: The µMPs were fed HcD supplemented with 0.7% CA (HcD＋CA) for eight weeks, and the effect of CA on serum lipoprotein levels, expression of oxidative stress markers, adiposity and lesion formation in the aorta, liver, and other organs was investigated. RESULTS: The HcD＋CA-fed group exhibited more visceral adiposity, progression of atherosclerosis and higher serum levels of oxidative stress markers than the HcD-fed group, even though they showed similar serum lipid levels. The liver demonstrated increased lipid accumulation, higher expression of oxidative stress markers, accelerated activation of foamy Kupffer cells and stellate cells, and increased hepatocyte apoptosis, indicating non-alcoholic fatty liver disease (NAFLD). Intriguingly, foamy macrophage mobilization was observed in various organs, including the reticuloendothelial system, pulmonary capillary vessels and skin very often in HcD＋CA-fed µMPs. CONCLUSION: To our knowledge, this is the first large animal model, in which visceral obesity, NAFLD and atherosclerosis are concomitantly induced by dietary manipulation. These data suggest the detrimental effects of CA, potentially through local and systemic activation of oxidative stress-induced signaling to macrophage mobilization, on the acceleration of visceral adiposity, atherosclerosis and NAFLD.

DOI： 10.5551/jat.39909

大田修平, 砂川剛, 島袋盛一, 満元洋二郎, 谷本昭英 . 経過中穿孔を来した成人T細胞性白血病リンパ腫の1例 . 癌と化学療法44 ( 12 ) 1494 - 1496 2017.11経過中穿孔を来した成人T細胞性白血病リンパ腫の1例

Publisher：(株)癌と化学療法社

成人T細胞性白血病リンパ腫(ATLL)は、全身諸臓器へ浸潤し、消化管へも高率に浸潤するが、穿孔を来すことはまれである。ATLLの消化管浸潤により、穿孔を来した症例を経験したため報告する。患者は腹部膨満感を主訴に受診した75歳、男性。腹部造影CTで回盲部に粗大な腫瘤を認め、下部消化管内視鏡検査では上行結腸に浮腫、狭窄があり、スコープは通過できず、上行結腸狭窄部肛門側に腫瘤を認めた。入院後、腹膜刺激症状を伴う腹痛が出現した。腹部造影CTで回盲部腫瘍周囲にfree airを認め、消化管穿孔の診断で緊急手術を施行した。術後の病理組織検査でATLLの消化管浸潤と診断された。ATLLの消化管浸潤は消化管穿孔を来すことがあり、穿孔を来した場合は予後不良である。ATLLの治療の主体は化学療法であるが、穿孔を来した場合は早急に手術が必要であり、慎重に経過をみる必要があると考えられた。(著者抄録)

Md Zahorul Islam, Hiroaki Kawaguchi, Naoki Miura, Noriaki Miyoshi, Emi Yamazaki-Himeno, Mitsuya Shiraishi, Atsushi Miyamoto, Akihide Tanimoto . Hypertension alters the endothelial-dependent biphasic response of bradykinin in isolated Microminipig basilar artery. . Microvascular research114 52 - 57 2017.11Hypertension alters the endothelial-dependent biphasic response of bradykinin in isolated Microminipig basilar artery.Reviewed International journal

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

Angiotensin (Ang) II is known to promote vascular disease and hypertension, partly through its effect on vascular endothelium. Bradykinin (BK) is an endothelium-dependent agonist that induces relaxation followed by contraction of the porcine basilar artery through release of NO and PGF2α, respectively. In this study, we evaluated the effect of Ang II-induced hypertension on basilar artery responsiveness to BK in the Microminipig (MMPig). Ang II (200ng/kg/min) or vehicle was infused into MMPigs for 14days using an osmotic mini-pump and blood pressure was monitored regularly. The responsiveness of subsequently isolated basilar arteries was then measured using a micro organ bath system. MMPig basilar artery endothelial cells were cultured and stimulated with Ang II or vehicle for 48h. Mean blood pressure was significantly (P<0.05; n=5) higher in Ang II-infused MMPigs than in vehicle-infused MMPigs. In vitro, BK-induced endothelium-dependent dilation of isolated basilar artery specimens was abolished and BK-induced contraction was significantly increased (Emax: 15.85±2.42% and 56.54±2.71% of 60mM KCl in control and Ang II group respectively at 10-7M concentration of BK; P<0.01; n=5) in Ang II-infused MMPigs. Ang II stimulation of the endothelial cells significantly decreased (54.15% at 24h; P<0.05; n=three independent experiment performed in triplicate) the amount of BK-elicited NO and increased (44.27% at 24h; P<0.05; n=three independent experiment performed in triplicate) the amount of BK-elicited PGF2α. These results suggest that the decrease of NO and increase of PGF2α production from endothelial cells are responsible for cerebrovascular dysfunction in hypertension, possibly causing cerebrovascular contraction and thus increasing the risk of brain infarction.

DOI： 10.1016/j.mvr.2017.06.001

Takashi Tasaki, Kazuhito Hatanaka, Mari Kirishima, Shun Ohnishi, Yuko Goto, Ikumi Kitazono, Tsubasa Hiraki, Sohsuke Yamada, Michiyo Higashi, Akihide Tanimoto . Aortic fibromuscular dysplasia complicated by dissection: a case report and review of literature . CARDIOVASCULAR PATHOLOGY31 41 - 46 2017.11Aortic fibromuscular dysplasia complicated by dissection: a case report and review of literatureReviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Fibromuscular dysplasia (FMD) is an idiopathic, segmental, nonatherosclerotic, non-inflammatory vascular disease, which is often complicated by the occurrence of dissection. Although it is known to occur in all arteries, aortic involvement is relatively rare. To date, 33 cases of aortic FMD have been reported in available English literature, among which only three cases have been complicated by the occurrence of dissection. We describe the case of a 40-year-old woman diagnosed with aortic FMD complicated by the occurrence of a type A aortic dissection. Non-invasive imaging revealed an ascending to descending thoracic aneurysm measuring 8 cm in diameter associated with dissection. Histopathologically, a segment of the wall of the aneurysm showed architectural disorganization of the aortic wall with loss of elastic fibers, collagen deposition, and irregular proliferation of smooth muscle cells in the intima and media-features suggesting FMD. No atheromatous plaque or medial cystic degeneration was observed in the aorta. Although aortic FMD is sometimes fatal, it is often very difficult to diagnose using imaging techniques. Therefore, performing a histopathological diagnosis is very important and should be emphasized. (C) 2017 Published by Elsevier Inc.

DOI： 10.1016/j.carpath.2017.07.007

Shuhei Ota, Tsuyoshi Sunagawa, Morikazu Shimabukuro, Youjirou Mitsumoto, Akihide Tanimoto . [Bowel Perforation in a Patient with Adult T-Cell Leukemia/Lymphoma]. . Gan to kagaku ryoho. Cancer & chemotherapy44 ( 12 ) 1494 - 1496 2017.11[Bowel Perforation in a Patient with Adult T-Cell Leukemia/Lymphoma].Reviewed

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

Adult T-cell leukemia/lymphoma(ATLL)can infiltrate throughout various organs and frequently involves the gastrointestinal tract. However, bowel perforation in ATLL patients is rare. Herein, we present a case of ATLL with bowel perforation. A 75-year-old man presented with bowel distension. Computed tomography showed a large mass of the cecum. Edema and stenosis of the ascending colon was seen on colonoscopy, and tumor on the anal side of the stenosis was also found. After admission, the patient complained of abdominal pain with a peritoneal irritation sign. Free air was seen around a large mass of the cecum on computed tomography and an emergency operation was performed under the diagnosis of bowel perforation. Microscopic examination revealed bowel infiltration of ATLL. Gastrointestinal perforation can be caused by ATLL itself and is associated with a poor prognosis. The standard treatment for ATLL is chemotherapy but emergency surgery is necessary in case of perforation. It is important to observe the patient with ATLL carefully.

Michiko Noguchi, Masaya Hirata, Hiroaki Kawaguchi, Akihide Tanimoto . Corpus luteum Regression Induced by Prostaglandin F-2 alpha in Microminipigs During the Normal Estrous Cycle . IN VIVO31 ( 6 ) 1097 - 1101 2017.11Corpus luteum Regression Induced by Prostaglandin F-2 alpha in Microminipigs During the Normal Estrous CycleReviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：INT INST ANTICANCER RESEARCH

Induction of corpus luteum regression and subsequent estrus using prostaglandin F-2 alpha (PGF(2 alpha)) in microminipigs was investigated. Microminipigs with normal estrous cycle were treated with PGF(2 alpha) as 0.75 mg (0.75 PG group, n=3) or 1.5 mg (1.5 PG group, n=4) dinoprost injected into the vulva at 24-h intervals at 10 days after the onset of estrus (D0), D1 and D2. Three microminipigs were not treated (control group). The estrous interval in the 1.5 PG group was significantly shortened compared to the control and 0.75 PG groups. Plasma progesterone levels started to decline and reached the base line in the 1.5 PG group significantly faster than in the control group. In conclusion, we demonstrate that multiple PGF(2 alpha) treatments can induce corpus luteum regression and estrous synchronization in female microminipigs.

DOI： 10.21873/invivo.11175

大田修平, 砂川剛, 島袋盛一, 満元洋二郎, 谷本昭英 . 経過中穿孔を来した成人T細胞性白血病リンパ腫の1例 . 癌と化学療法44 ( 12 ) 1494 - 1496 2017.11Reviewed

Authorship：Last author Language：Japanese Publisher：(株)癌と化学療法社

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00296&link_issn=&doc_id=20171221480149&doc_link_id=%2Fab8gtkrc%2F2017%2F004412%2F149%2F1494-1496%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2017%2F004412%2F149%2F1494-1496%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Takuya Yoshimura, Sohsuke Yamada, Takayuki Ishida, Kazuhiko Tanaka, Ikumi Kitazono, Kenichi Kume, Hiroshi Hijioka, Ichiro Semba, Norifumi Nakamura, Akihide Tanimoto . Cystadenocarcinoma of the minor salivary gland arising in the upper lip: A surgical case of an inadequate cytology specimen hampering conclusive diagnosis . Human Pathology: Case Reports9 64 - 68 2017.9Reviewed

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

Cystadenocarcinoma (CAC) of the salivary gland poses a diagnostic challenge to us, as this uncommon entity is extremely difficult to diagnose pre-operatively on an inadequate sample. However, markedly few papers have described the cytological features of CAC. An 82-year-old male presented with a history of a gradual increase in size and occasional mucous drainage from a swollen reddish nodule on the right upper lip. A retrospective examination of the cytological specimens from the drainage revealed a small number of clusters and scattered single cells of severely degenerated and mildly atypical epithelial cells with hyperchromatic dense nuclei and abundant clear cytoplasm, in a background of a large amount of mucinous material. We first interpreted this finding merely as the presence of atypical cells. However, a gross examination revealed a non-capsulated and relatively well-demarcated cystic lesion, grayish to whitish in color and measuring 13 × 9 mm in diameter, filled with mucin. A microscopic examination showed that the tumor had a central cystic cavity filled with mucinous material and was predominantly composed of the papillary proliferation of atypical columnar mucous epithelial cells with enlarged hyperchromatic nuclei, mixed with mitotic hot spots often projecting and melting into the mucinous cystic lumen, and focally involving the surrounding connective tissue. Therefore, we ultimately made a diagnosis of CAC of the minor salivary gland arising in the upper lip. Given the characteristic features of CAC, cytopathologists should be able to correctly diagnose this lesion based on multiple adequate fine needle aspiration samples.

DOI： 10.1016/j.ehpc.2016.08.006

Scopus

J-GLOBAL

谷本昭英, 山田壮亮 . 【血管生物学と疾患】日常業務でよく遭遇する血管病変の最新知見粥状動脈硬化症の最新知見と病理 . 病理と臨床35 ( 8 ) 700 - 706 2017.8

Tsubasa Hiraki, Kazuhito Hatanaka, Kazunobu Sueyoshi, Yuko Goto, Ikumi Kitazono, Mari Kirishima, Sohsuke Yamada, Michiyo Higashi, Akihide Tanimoto . Unusual morphology of a pulmonary blastoma having an epithelial component with focally significant nuclear pleomorphism. . Pathology international67 ( 7 ) 370 - 372 2017.7Unusual morphology of a pulmonary blastoma having an epithelial component with focally significant nuclear pleomorphism.Reviewed International journal

宿里亜李沙, 田中和彦, 窪田恵美, 竹下かおり, 西田ゆかり, 平木翼, 山田壮亮, 東美智代, 畑中一仁, 谷本昭英 . 腎細胞癌根治術後20年で甲状腺内孤立性転移を来たした1例 . 日本臨床細胞学会九州連合会雑誌48 89 - 93 2017.7腎細胞癌根治術後20年で甲状腺内孤立性転移を来たした1例

Publisher：日本臨床細胞学会-九州連合会

背景:術後長期を経た腎細胞癌の甲状腺への孤立性転移は非常に稀である。今回、我々は右腎細胞癌術後20年を経過して甲状腺内に孤立性転移を来たした症例を経験したので報告する。症例:70歳代、男性。前医のエコー検査にて甲状腺右葉内に45×41×32mm大の腫瘤を指摘され、当院を紹介受診された。穿刺吸引細胞診では、血性背景に濃縮コロイドや濾胞上皮細胞集塊に混じて、異型細胞が孤在性からシート状にごく少数認められた。異型細胞は淡明で豊富な細胞質と軽度腫大した核を有し、N/C比は小さいながらも核形不整と中心性の明瞭な核小体を認めた。異型細胞はごく少数で、且つ由来が不明であったため、「鑑別困難」(現:意義不明)と報告したところ、経過観察となっていた。その後、嗄声が出現したため再受診され、甲状腺癌による右反回神経麻痺と診断された。生検の結果、腎細胞癌の転移と判明し、CTにて周囲組織への広汎な浸潤が疑われたため、甲状腺全摘出術及び喉頭摘出術が施行された。結論:再検討では淡明細胞型腎細胞癌の細胞像であり、スクリーニング時に充分な情報があれば、腎細胞癌の転移を指摘しえた症例であった。甲状腺の単発性腫瘤であっても、病歴に留意し、腎細胞癌の転移も念頭においたスクリーニングが望まれる。(著者抄録)

宿里亜李沙, 田中和彦, 窪田恵美, 竹下かおり, 西田ゆかり, 平木翼, 山田壮亮, 東美智代, 畑中一仁, 谷本昭英 . 腎細胞癌根治術後20年で甲状腺内孤立性転移を来たした1例 . 日本臨床細胞学会九州連合会雑誌48 89 - 93 2017.7腎細胞癌根治術後20年で甲状腺内孤立性転移を来たした1例Reviewed

Authorship：Last author Language：Japanese Publisher：日本臨床細胞学会-九州連合会

Tsubasa Hiraki, Sohsuke Yamada, Michiyo Higashi, Kazuhito Hatanaka, Seiya Yokoyama, Ikumi Kitazono, Yuko Goto, Mari Kirishima, Surinder K. Batra, Suguru Yonezawa, Akihide Tanimoto . Immunohistochemical expression of mucin antigens in gallbladder adenocarcinoma: MUC1-positive and MUC2-negative expression is associated with vessel invasion and shortened survival . HISTOLOGY AND HISTOPATHOLOGY32 ( 6 ) 585 - 596 2017.6Immunohistochemical expression of mucin antigens in gallbladder adenocarcinoma: MUC1-positive and MUC2-negative expression is associated with vessel invasion and shortened survivalReviewed International journal

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

Mucins play pivotal roles in influencing cancer biology, for example affecting carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to investigate the significance of expression profiles of two mucins in particular, MUC1 and MUC2, their correlations with various clinicopathological features, and prognosis in gallbladder adenocarcinoma (GBAC). We performed immunohistochemistry from patients with surgically resected GBAC, using antibodies against mucin core proteins MUC1/DF3 and MUC2/Ccp58 in 81 paraffin-embedded tumor samples. MUC1 or MUC2 expression was considered to be high when >= 20% or 10% of the GBAC cells showed positive staining, respectively. High MUC1 expression was revealed to have a significant relationship to the presence of pathologically lymphatic and vascular invasion, and regional lymph node metastasis. By contrast, high MUC2 expression showed a significant correlation with pathologically perineural invasion, T stage >= 3, and post-operative recurrence. Moreover, MUC1 showed significantly positive co-expression and potentially complementary correlations with MUC2. Multivariate analyses demonstrated that the high MUC1 expression group had significantly shorter disease-specific survival times. However, the combination of both high MUC1 and MUC2 expression did not predict worse outcome in GBACs. Therefore, although each mucin has a somewhat important role in the pathogenesis of GBAC progression, MUC1 can independently predict vessel invasion and poor prognosis in patients with GBAC. The detection of MUC1 might well offer a useful parameter for providing clinical management and treatment against postsurgical GBACs.

DOI： 10.14670/HH-11-824

Mika Kina-Tanada, Mayuko Sakanashi, Akihide Tanimoto, Tadashi Kaname, Toshihiro Matsuzaki, Katsuhiko Noguchi, Taro Uchida, Junko Nakasone, Chisayo Kozuka, Masayoshi Ishida, Haruaki Kubota, Yuji Taira, Yuichi Totsuka, Shin-Ichiro Kina, Hajime Sunakawa, Junichi Omura, Kimio Satoh, Hiroaki Shimokawa, Nobuyuki Yanagihara, Shiro Maeda, Yusuke Ohya, Masayuki Matsushita, Hiroaki Masuzaki, Akira Arasaki, Masato Tsutsui . Long-term dietary nitrite and nitrate deficiency causes the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice. . Diabetologia60 ( 6 ) 1138 - 1151 2017.6Long-term dietary nitrite and nitrate deficiency causes the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice.Reviewed International journal

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

AIMS/HYPOTHESIS: Nitric oxide (NO) is synthesised not only from L-arginine by NO synthases (NOSs), but also from its inert metabolites, nitrite and nitrate. Green leafy vegetables are abundant in nitrate, but whether or not a deficiency in dietary nitrite/nitrate spontaneously causes disease remains to be clarified. In this study, we tested our hypothesis that long-term dietary nitrite/nitrate deficiency would induce the metabolic syndrome in mice. METHODS: To this end, we prepared a low-nitrite/nitrate diet (LND) consisting of an amino acid-based low-nitrite/nitrate chow, in which the contents of L-arginine, fat, carbohydrates, protein and energy were identical with a regular chow, and potable ultrapure water. Nitrite and nitrate were undetectable in both the chow and the water. RESULTS: Three months of the LND did not affect food or water intake in wild-type C57BL/6J mice compared with a regular diet (RD). However, in comparison with the RD, 3 months of the LND significantly elicited visceral adiposity, dyslipidaemia and glucose intolerance. Eighteen months of the LND significantly provoked increased body weight, hypertension, insulin resistance and impaired endothelium-dependent relaxations to acetylcholine, while 22 months of the LND significantly led to death mainly due to cardiovascular disease, including acute myocardial infarction. These abnormalities were reversed by simultaneous treatment with sodium nitrate, and were significantly associated with endothelial NOS downregulation, adiponectin insufficiency and dysbiosis of the gut microbiota. CONCLUSIONS/INTERPRETATION: These results provide the first evidence that long-term dietary nitrite/nitrate deficiency gives rise to the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice, indicating a novel pathogenetic role of the exogenous NO production system in the metabolic syndrome and its vascular complications.

DOI： 10.1007/s00125-017-4259-6

Ke-Yong Wang, Sohsuke Yamada, Shohei Shimajiri, Ryuji Nakano, Naoki Yamashita, Tetsuya So, Akihide Tanimoto . Calcifying giant cell cardiomyopathy: a possible new entity. Images in Cardiovascular Pathology . CARDIOVASCULAR PATHOLOGY28 68 - 70 2017.5Calcifying giant cell cardiomyopathy: a possible new entity. Images in Cardiovascular PathologyReviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

We demonstrated an extremely unusual case of an 83-year-old male's sudden death secondary to characteristic myocardial necrosis and fibrosis with calcification and multinucleated giant cells infiltration, possibly due to sepsis and Stage IV pulmonary pleomorphic carcinoma-induced cachexia after postmortem study. We propose that this calcifying giant cell cardiomyopathy (CGC) would be a new entity especially from the pathological viewpoints and should be considered in the classification of noninfectious myocarditis. Further prospective studies are needed to validate the presence and significance of CGC and the association with any triggers of somewhat microvascular dysfunction and/or toxic agents, after collecting and investigating a larger number of CGC cases examined. (C) 2017 The Authors. Published by Elsevier Inc.

DOI： 10.1016/j.carpath.2017.03.004

Yuko Higashi, Takako Yoshioka, Kazuhiro Kawai, Kazuyasu Fujii, Makoto Yoshimitsu, Joji Kusuyama, Kaori Shima, Akihide Tanimoto, Takuro Kanekura . Lymphomatoid granulomatosis initially presenting as ulcerated subcutaneous and muscle lesions without pulmonary involvement. . The Journal of dermatology44 ( 5 ) e107 - e108 2017.5Lymphomatoid granulomatosis initially presenting as ulcerated subcutaneous and muscle lesions without pulmonary involvement.Reviewed International journal

Sohsuke Yamada, Hirotsugu Noguchi, Akihide Tanimoto . Critical and diverse in vivo roles of apoptosis signal-regulating kinase 1 in animal models of atherosclerosis and cholestatic liver injury . HISTOLOGY AND HISTOPATHOLOGY32 ( 5 ) 433 - 444 2017.5Critical and diverse in vivo roles of apoptosis signal-regulating kinase 1 in animal models of atherosclerosis and cholestatic liver injuryReviewed International journal

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

Apoptosis plays pivotal in vivo roles in not only vital processes, such as cell turnover and embryonic development, but also various inflammatory disorders. However, the role of apoptosis by vascular and hepatic cells in the respective progression of atherosclerosis and liver injury remains controversial. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase family member that is activated through distinct mechanisms in response to various cytotoxic stressors. ASK1, ubiquitously expressed, is situated in an important upstream position for many signal transduction pathways, which subsequently induce inflammation and/or apoptosis. Our serial in vivo studies have uniquely reported that the expression of phosphorylated ASK1 is variably seen in atherosclerotic lesions or bile-duct- ligation (BDL)induced injury livers. In mice genetically deficient of ASK1 (ASK1(-/-)), activated ASK1 signaling accelerates high-cholesterol-diet-induced necrotic lipid core formation by inducing macrophage apoptosis and enhances ligation injury-induced vascular remodeling via pro-inflammatory reactions and by stimulating apoptosis of smooth muscle cells. In contrast, in models of BDL-induced cholestatic liver injury, the pathogenic roles of ASK1-mediated early necro-inflammation, but not apoptosis, and the proliferation of hepatocytes and cholangiocytes are crucial in subsequent peribiliary fibrosis/fibrogenesis. These animal models of acute to chronic inflammatory diseases show that stimulated ASK1 signaling critically and diversely regulates not only hypercholesterolemia-induced atherosclerosis and injury-induced arteriosclerosis, but also the acute and subacute-to-chronic phase of BDL-induced cholestasis. We herein review the diverse, key in vivo roles of ASK1 signaling in the pathogenesis of inflammatory disorders closely related to metabolic syndrome.

DOI： 10.14670/HH-11-840