Faculty Profiles - akihide Tanimoto

Papers - akihide Tanimoto

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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 2017.6Reviewed 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 2017.6Reviewed 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 2017.5Reviewed 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 2017.5Reviewed 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 2017.5Reviewed 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

平木翼, 山田壮亮, 霧島茉莉, 後藤優子, 北薗育美, 畑中一仁, 東美智代, 谷本昭英 . 基底細胞腺腫、篩状亜型の1例 . 診断病理34 ( 2 ) 102 - 105 2017.4

Publisher：(一社)日本病理学会

40代、男性。右耳下腺部に20mm大の可動性良好な腫瘤を認め、摘出術が施行された。周囲とは境界明瞭で、一部に菲薄な線維性被膜を認めた。病変の大部分は基底細胞様細胞が大小の篩状構造を呈し増殖しており、胞巣内には好酸性細胞質を有する導管上皮様細胞からなる真の腺腔も散見された。腺様嚢胞癌や基底細胞腺癌等、篩状構造を示す悪性上皮性唾液腺腫瘍との鑑別が問題となったが、肉眼的に境界明瞭な病変であり、組織学的にも明らかな浸潤性増殖や神経侵襲、脈管侵襲を認めない事から基底細胞腺腫、篩状亜型と診断した。(著者抄録)

平木翼, 山田壮亮, 霧島茉莉, 後藤優子, 北薗育美, 畑中一仁, 東美智代, 谷本昭英 . 基底細胞腺腫、篩状亜型の1例 . 診断病理34 ( 2 ) 102 - 105 2017.4Reviewed

Authorship：Last author Language：Japanese Publisher：(一社)日本病理学会

40代、男性。右耳下腺部に20mm大の可動性良好な腫瘤を認め、摘出術が施行された。周囲とは境界明瞭で、一部に菲薄な線維性被膜を認めた。病変の大部分は基底細胞様細胞が大小の篩状構造を呈し増殖しており、胞巣内には好酸性細胞質を有する導管上皮様細胞からなる真の腺腔も散見された。腺様嚢胞癌や基底細胞腺癌等、篩状構造を示す悪性上皮性唾液腺腫瘍との鑑別が問題となったが、肉眼的に境界明瞭な病変であり、組織学的にも明らかな浸潤性増殖や神経侵襲、脈管侵襲を認めない事から基底細胞腺腫、篩状亜型と診断した。(著者抄録)

Seiya Yokoyama, Michiyo Higashi, Hideaki Tsutsumida, Jouji Wakimoto, Tomofumi Hamada, Edwin Wiest, Kei Matsuo, Ikumi Kitazono, Yuko Goto, Xin Guo, Taiji Hamada, Sohsuke Yamada, Tsubasa Hiraki, Suguru Yonezawa, Surinder K Batra, Michael A Hollingsworth, Akihide Tanimoto . TET1-mediated DNA hypomethylation regulates the expression of MUC4 in lung cancer. . Genes & cancer8 ( 3-4 ) 517 - 527 2017.3Reviewed International journal

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

Lung cancer remains a disease of high mortality, despite advanced diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in lung neoplasms. Our immunohistochemistry (IHC) studies have shown that high MUC4 expression correlates with a poor outcome. We have also shown that the expression of several mucin genes in cancer cell lines is regulated by DNA methylation. We evaluated the expression level of MUC4, mRNA and several DNA hypomethylation factors in lung tissue samples from 33 patients with various lung lesions. The results indicated that the DNA methylation status of MUC4 matched the expression level of mRNA. In addition, the TET1 (Ten-Eleven Translocation) mRNA showed a significant correlation with the status of DNA methylation of MUC4. Furthermore, the treatment of a lung cancer cell line with TET1 siRNA caused a reduction in MUC4 mRNA expression. Thus, we suggest that TET1 mediated DNA hypomethylation plays a key role in the expression of MUC4. This is the first report that TET1 mediated DNA hypomethylation regulates the expression of MUC4 in lung cancer. The analysis of these epigenetic changes may be useful for diagnosing carcinogenic risk.

DOI： 10.18632/genesandcancer.139

Xin Guo, Zhiming Dong, Sohsuke Yamada, Yuanyuan Li, Yanli Guo, Supeng Shen, Jia Liang, Akihide Tanimoto, Wei Guo . Association of Casp3 microRNA Target Site (1049216) SNP With the Risk and Progress of Cervical Squamous Cell Carcinoma. . International journal of gynecological cancer : official journal of the International Gynecological Cancer Society27 ( 2 ) 206 - 213 2017.2Reviewed International journal

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

OBJECTIVE: In the present study, we investigated the relationship between the single-nucleotide polymorphism (SNP) of caspase-3 rs1049216 (C > T), a miRNA target site, and the risk and progression of cervical cancer. MATERIALS AND METHODS: Using polymerase chain reaction-restriction fragment length polymorphism, we evaluated the genotype and distribution of caspase-3 rs1049216 in 515 patients with cervical squamous cell cancer and 415 controls. In additional experiments, we transfected luciferase reporter plasmids carrying T or C allele and/or miRNA mimics into the human cervical cell lines (HeLa and C-33A) to analyze its roles in the regulation of caspase-3 expression. By immunohistochemistry, the protein level of caspase-3 expression was examined in tumor tissues from 515 patients with cervical squamous cell cancer. RESULTS: We found that the TT genotype of caspase-3 rs1049216 conferred a significantly decreased risk of cervical cancer (adjusted odds ratio, 0.35; 95% confidence interval, 0.154-0.581) and may be associated with the progression of this cancer. Although the expression of caspase-3 in the TT genotype was higher than that in CC/CT genotype in peripheral blood mononuclear cells and tumor tissues. Additional luciferase analysis showed that the rs1049216 variant T allele was associated with significantly higher luciferase activity, compared with the C allele in the transfected cells, and when cotransfected with miRNAs, miRNA-181a could downregulate the luciferase activity in the cells that transfected the construct containing C allele, compared with T allele, which had not happened in the presence of other miRNAs selected. CONCLUSIONS: These data indicate that through upregulating the expression of caspase-3, the TT genotype of caspase-3 rs1049216 can be associated with not only the risk of cervical cancer but also the progression of this cancer.

DOI： 10.1097/IGC.0000000000000881

筒井正人, 下川宏明, 谷本昭英, 柳原延章, 尾辻豊 . NOと代謝・循環器・腎臓疾患 NOSs完全欠損マウスの解析から . 腎臓内科・泌尿器科5 ( 2 ) 177 - 184 2017.2

Kan Tanabe, Yoshinari Shinsato, Tatsuhiko Furukawa, Yoshiaki Kita, Kazuhito Hatanaka, Kentaro Minami, Kohichi Kawahara, Masatatsu Yamamoto, Kenji Baba, Shinichiro Mori, Yasuto Uchikado, Kosei Maemura, Akihide Tanimoto, Shoji Natsugoe . Filamin C promotes lymphatic invasion and lymphatic metastasis and increases cell motility by regulating Rho GTPase in esophageal squamous cell carcinoma. . Oncotarget8 ( 4 ) 6353 - 6363 2017.1Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：IMPACT JOURNALS LLC

To establish treatments to improve the prognosis of cancer patients, it is necessary to find new targets to control metastasis. We found that expression of FilaminC (FLNC), a member of the actin binding and cross-linking filamin protein family is correlated with lymphatic invasion and lymphatic metastasis in esophageal squamous cell carcinoma (ESCC) by increasing cell motility through activation of Rho GTPase.Immunohistochemistry analysis showed that FLNC expression in ESCC is associated with lymphatic invasion, metastasis, and prognosis. FLNC knockdown in esophageal cancer cell lines decreased cell migration in wound healing and transwell migration assays, and invasion in transwell migration assays. Furthermore, FLNC knockdown reduced the amount of activated Rac-1 (GTP-Rac1) and activated Cdc42 (GTP-Cdc42). Our results suggest that FLNC expression is a useful biomarker of ESCC metastatic tendency and that inhibiting FLNC function may be useful to control the metastasis of ESCC.

DOI： 10.18632/oncotarget.14087

Sohsuke Yamada, Mari Kirishima, Tsubasa Hiraki, Michiyo Higashi, Kazuhito Hatanaka, Akihide Tanimoto . Epithelioid schwannoma of the skin displaying unique histopathological features: a teaching case giving rise to diagnostic difficulties on a morphological examination of a resected specimen, with a brief literature review. . Diagnostic pathology12 ( 1 ) 11 - 11 2017.1Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：BIOMED CENTRAL LTD

BACKGROUND: Epithelioid schwannoma as a rare variant poses a challenge to all pathologists, as this uncommon entity is extremely difficult to conclusively diagnose by morphological analyses on a resected sample alone owing to its unique histopathological features. However, few papers have described the detailed clinicopathological characteristics of epithelioid schwannoma. CASE PRESENTATION: A 65-year-old female presented with a history of a flat and slightly elevated firm and tan plaque accompanied by occasional tenderness, measuring 10 × 8 mm, in the right joint of her hand 1 year before resection. A gross examination of a locally resected specimen revealed an encapsulated nodular lesion, yellow-whitish in color, partly filled with blood. A microscopic examination showed that the tumor predominantly consisted of a solid proliferation of epithelioid cells having mildly enlarged and round to partially spindled nuclei and abundant vacuolated or clear cytoplasm with very few mitotic figures and modest nuclear size variation, associated with focal hyalinized, cystic and hemorrhagic degeneration. This well-demarcated tumor was surrounded by dense, hyalinized and layered fibrocollagenous stroma. Immunohistochemically, these tumor cells were diffusely positive for S-100 protein and had a very low MIB-1 labeling index, and type IV collagen was strongly reactive with reduplicated basal lamina of them. We ultimately made a diagnosis of cutaneous epithelioid schwannoma. CONCLUSION: We should be aware that, since pathologists might misinterpret epithelioid schwannoma as other soft tissue tumors, including its malignant counterpart, a wide panel of immunohistochemical antibodies can be powerful supplementary tools for identifying a very rare entity of conventional schwannoma.

DOI： 10.1186/s13000-017-0604-9

喜名美香, 坂梨まゆ子, 谷本昭英, 松崎俊博, 野口克彦, 仲宗根淳子, 下川宏明, 喜名振一郎, 砂川元, 大屋祐輔, 新崎章, 筒井正人 . 食事中のnitriteおよびnitrateの不足は代謝症候群、内皮機能不全、および心血管死を惹起する . 血管40 ( 1 ) 60 - 60 2017.1

Hozaka Yuto, Tanimoto Akihide, Shinchi Hiroyuki, Natsugoe Shoji, Mori Shinichiro, Baba Kenji, Kita Yoshiaki, Mataki Yuko, Uenosono Yoshikazu, Uchikado Yasuto, Maemura Kosei, Kitazono Ikumi . Mixed Connective Tissue Disease with Cecal Volvulus and Secondary Ileal Volvulus . The Japanese Journal of Gastroenterological Surgery50 ( 12 ) 1008 - 1015 2017Reviewed

Language：Japanese Publisher：The Japanese Society of Gastroenterological Surgery

<p>A 60-year-old woman with mixed connective tissue disease (MCTD) was admitted because of abdominal pain and vomiting. Abdominal CT showed "whirl sign" around the cecum, so the patient was given a diagnosis of cecal volvulus. The patient underwent emergency operation. The cecum was twisted 360° clockwise around the ileocolic vessels. Although the jejunum and ileum were dilated, the cecum and intestine caused no ischemic change. The patient underwent detorsion of the cecum and cecopexy. The patient was discharged twelve days after surgery. Thirty-seven days after discharge, the patient was admitted for abdominal pain again. The patient underwent emergency operation since we diagnosed recurrence cecum volvulus. The ileum twisted 360° clockwise and detorsion of the twisting ileum was performed. We decided to reoperate the intestinal resection after decompression treatment, because the patient had a possibility of ileal volvulus again. Fifty-one days later from the initial surgery, we operated again. We resected the extended ileum 30 cm. Atrophy of the muscle layer was observed corresponding to the extend site pathologically. There was some possibility of hypoperistalsis due to atrophy of intestinal muscle of MCTD. It is better to evaluate peristalsis using gastrointestinal series in case of bowel volvulus with MCTD.</p>

DOI： 10.5833/jjgs.2016.0186

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J01117&link_issn=&doc_id=20180115390010&doc_link_id=10.5833%2Fjjgs.2016.0186&url=https%3A%2F%2Fdoi.org%2F10.5833%2Fjjgs.2016.0186&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Sohsuke Yamada, Akihide Tanimoto, Yasuyuki Sasaguri . Critical in vivo roles of histamine and histamine receptor signaling in animal models of metabolic syndrome. . Pathology international66 ( 12 ) 661 - 671 2016.12Reviewed International journal

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

Histamine, a classic low-molecular-weight amine, is synthesized from L-histidine by histidine decarboxylase (HDC), and histamine-specific receptors (HRs) are essential for its actions. Our serial in vivo studies have uniquely reported that expression of histamine/HRs is variably identified in atherosclerotic lesions, and that HDC-gene knockout mice without histamine/HRs signaling show a marked reduction of atherosclerotic progression. These data have convinced us that histamine plays a pivotal role in the pathogenesis of atherosclerosis. Among four subclasses of HRs, the expression profile of the main receptors (H1/2R) has been shown to be switched from H2R to H1R during monocyte to macrophage differentiation, and H1R is also predominant in smooth muscle and endothelial cells of atheromatous plaque. Using various animal models of H1/2R-gene knockout mice, H1R and H2R were found to reciprocally but critically regulate not only hypercholesterolemia-induced atherosclerosis and injury-induced arteriosclerosis, but also hyperlipidemia-induced nonalcoholic fatty liver disease (NAFLD). Metabolic syndrome manifests obesity, dyslipidemia, insulin resistance, atherosclerosis, and/or NAFLD, i.e. the dysregulation of lipid/bile acid/glucose metabolism. Therefore, although its etiology is complicated and multifactorial, histamine/HRs signaling has a close relationship with the development of metabolic syndrome. We herein review diverse, key in vivo roles of histamine/HR signaling in the pathogenesis of metabolic syndrome.

DOI： 10.1111/pin.12477

Waka Yamada, Tatsuru Kaji, Shun Onishi, Kazuhiko Nakame, Koji Yamada, Takafumi Kawano, Motoi Mukai, Masakazu Souda, Takako Yoshioka, Akihide Tanimoto, Satoshi Ieiri . Ghrelin improves intestinal mucosal atrophy during parenteral nutrition: An experimental study. . Journal of pediatric surgery51 ( 12 ) 2039 - 2043 2016.12Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：W B SAUNDERS CO-ELSEVIER INC

BACKGROUND/PURPOSE: Total parenteral nutrition (TPN) has been reported to be associated with mucosal atrophy of the small intestine. Ghrelin has hormonal, orexigenic, and metabolic activities. We investigated whether ghrelin improved intestinal mucosal atrophy using a TPN-supported rat model. METHODS: Rats underwent jugular vein catheterization and were divided into four groups: TPN alone (TPN), TPN plus low-dose ghrelin (TPNLG), TPN plus high-dose ghrelin (TPNHG), and oral feeding with normal chow (OF). Ghrelin was administered continuously at dosages of 10 or 50 μg/kg/day. On day 6 rats were euthanized, and the small intestine was harvested and divided into the jejunum and ileum. Then the villus height (VH) and crypt depth (CD) were evaluated. RESULTS: The jejunal and ileal VH and CD in the TPN group were significantly decreased compared with those in the OF group. TPNHG improved only VH of the jejunum. TPNLG improved VH and CD of the jejunum and CD of the ileum. The improvement of TPNLG was significantly stronger than that in CD of the jejunum and ileum. CONCLUSIONS: TPN was more strongly associated with mucosal atrophy in the jejunum than in the ileum. Low-dose intravenous administration of ghrelin improved TPN-associated intestinal mucosal atrophy more effectively than high-dose administration.

DOI： 10.1016/j.jpedsurg.2016.09.035

Shun Onishi, Tatsuru Kaji, Waka Yamada, Kazuhiko Nakame, Tomoe Moriguchi, Koushirou Sugita, Koji Yamada, Takafumi Kawano, Motoi Mukai, Masakazu Souda, Sohsuke Yamada, Takako Yoshioka, Akihide Tanimoto, Satoshi Ieiri . The administration of ghrelin improved hepatocellular injury following parenteral feeding in a rat model of short bowel syndrome . PEDIATRIC SURGERY INTERNATIONAL32 ( 12 ) 1165 - 1171 2016.12Reviewed International journal

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

Long-term parenteral nutrition following massive bowel resection causes liver dysfunction, such as intestinal failure-associated liver disease (IFALD). IFALD includes two different states, cholestasis and steatosis, which represents a life-threatening complication. The previous reports have shown the protective role of ghrelin in the liver. The aim of this study was to evaluate the effects of the administration of ghrelin in the liver in a parenterally fed rat model of short bowel syndrome (SBS).
Rats underwent jugular vein catheterization, and were divided into three groups: 90 % small bowel resection (90 % SBR) and TPN (SBS/TPN group), 90 % SBR and TPN plus ghrelin (SBS/TPN/ghrelin group), and sham operation with normal chow (sham group). Ghrelin was administered continuously at a dose of 10 mu g/kg/day. On day 13, all rats were euthanized. The serum chemistry was analyzed, the lipid content of the liver was measured, and the liver tissue was histologically analyzed.
The AST and LDH levels significantly increased, and the accumulation of lipids in the liver was observed in the TPN/SBS group. The accumulation of lipids in the liver of the rats in the SBS/TPN group was attenuated by the administration of ghrelin.
The administration of ghrelin has a therapeutic potential for IFALD.

DOI： 10.1007/s00383-016-3975-1

坂江遥, 玉井努, 小田耕平, 鈴木紳介, 平木翼, 谷山央樹, 伊集院翔, 大西容雅, 椨一晃, 室町香織, 馬渡誠一, 森内昭博, 石塚賢治, 谷本昭英, 井戸章雄 . 脾破裂を伴い急性肝不全様の経過を呈した悪性リンパ腫の一例 . 肝臓57 ( 12 ) 674 - 683 2016.12Reviewed

Language：Japanese Publisher：(一社)日本肝臓学会

症例は66歳、男性。全身倦怠感、発熱、腹痛、食思不振で近医を受診し、血小板減少、肝腎機能障害を認め、当院へ緊急入院となった。腹部超音波検査、CT検査で著明な肝脾腫と脾内占拠性病変、脾出血を認めた。急速に肝不全が進行、播種性血管内凝固症候群(disseminated intravascular coagulation:DIC)も合併し、全身状態は増悪した。第3病日には腹腔内出血を来し、第5病日に死亡した。家族の同意を得て、剖検を行った。肝腫大、著明な脾腫大を認め、脾臓は被膜の破綻、出血を伴い脾破裂をきたしていた。肝臓、脾臓には腫瘍細胞がびまん性に増殖しており、免疫染色にて悪性リンパ腫(diffuse large B-cell lymphoma:DLBCL)と診断した。今回、我々は脾破裂を伴い急性肝不全様の急激な経過を呈した悪性リンパ腫の一例を経験したので文献的考察を含めて報告する。(著者抄録)

DOI： 10.2957/kanzo.57.674

Kazuchika Miyoshi, Hiroaki Kawaguchi, Kosuke Maeda, Masahiro Sato, Kohei Akioka, Michiko Noguchi, Masahisa Horiuchi, Akihide Tanimoto . Birth of Cloned Microminipigs Derived from Somatic Cell Nuclear Transfer Embryos That Have Been Transiently Treated with Valproic Acid. . Cellular reprogramming18 ( 6 ) 390 - 400 2016.11Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：MARY ANN LIEBERT, INC

In our previous study, we found that treatment of miniature pig somatic cell nuclear transfer (SCNT) embryos with 4 mM valproic acid (VPA), a histone deacetylase inhibitor, for 48 hours after activation enhanced blastocyst formation rate and octamer-binding transcription factor-3/4 (Oct-3/4) gene expression at the late blastocyst stage; however, the production of viable cloned pups failed, when those VPA-treated SCNT embryos were transferred to recipients. This failure suggests that the present VPA treatment is suboptimal. In the present study, we explored the optimal conditions for VPA to have beneficial effects on the development of SCNT embryos. When miniature pig SCNT embryos were treated with 8 mM VPA for 24 hours after activation, both the rates of blastocyst formation and blastocysts expressing the Oct-3/4 gene were significantly (p < 0.05) improved. A similar increase in blastocyst formation was also observed when microminipig-derived cells were used as SCNT donors. Five cloned piglets were obtained after the transfer of 152 microminipig SCNT embryos that had been treated with 8 mM VPA for 24 hours. The results indicated that a short duration of treatment with VPA improves the development of both miniature pig and microminipig SCNT embryos, possibly via an enhanced reprogramming mechanism.

DOI： 10.1089/cell.2016.0025

田崎貴嗣, 畑中一仁, 平木翼, 北薗育美, 後藤優子, 霧島茉莉, 山田壮亮, 東美智代, 宮園明典, 谷本昭英 . フィンランド型先天性ネフローゼ症候群の1症例 . 診断病理33 ( 4 ) 320 - 324 2016.10Reviewed

Language：Japanese Publisher：(一社)日本病理学会

稀なフィンランド型先天性ネフローゼ症候群の1例を報告する。症例は4ヵ月、男児。緊急帝王切開により出生した低出生体重児で、出生直後より低アルブミン血症、高蛋白尿、発育不良、浮腫、甲状腺機能低下症、脂質異常症および胸腹水を認めたが、腎機能低下はみられなかった。蛋白尿コントロール目的に片腎摘出術が行われた。腎は腫大し、組織学的には特徴的な小嚢胞状に拡張した尿細管が皮質表層から皮髄境界部にかけて認められ、糸球体メサンギウム細胞の増加がみられた。また本疾患の責任遺伝子であるNPHS1遺伝子変異が確認された。(著者抄録)

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