Faculty Profiles - akihide Tanimoto

Papers - akihide Tanimoto

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田崎貴嗣, 平木翼, 北薗育美, 後藤優子, 霧島茉莉, 山田壮亮, 東美智代, 畑中一仁, 東裕子, 金蔵拓郎, 谷本昭英 . 四肢遠位側に多発したEccrine angiomatous hamartomaの1症例 . 診断病理33 ( 4 ) 325 - 328 2016.10Reviewed

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

Eccrine angiomatous hamartomaの1症例を報告する。症例は12歳男児。1年前より両手指背と右足背に多発する、淡紅色の結節が指摘された。自覚症状はなく、胼胝を疑われ、足背の皮疹から生検された。組織学的に、真皮中層から皮下脂肪組織にかけて、粘液腫状変性を示す線維性間質を背景に、境界不明瞭な結節性病変を認めた。病変部ではエクリン腺や導管が増加し、周囲に毛細血管の増生や脂肪組織、末梢神経線維の混在を認めた。(著者抄録)

筒井正人, 迎寛, 矢寺和博, 谷本昭英, 下川宏明, 尾辻豊 . 一酸化窒素合成酵素の多様な役割 . 血管39 ( 3 ) 81 - 91 2016.9

Michiko Noguchi, Tomonobu Ikedo, Hiroaki Kawaguchi, Akihide Tanimoto . Estrus synchronization in microminipig using estradiol dipropionate and prostaglandin F-2 alpha . The Journal of Reproduction and Development62 ( 4 ) 373 - 378 2016.8Reviewed

Language：English Publishing type：Research paper (scientific journal) Publisher：SOCIETY REPRODUCTION & DEVELOPMENT-SRD

The induction of pseudopregnancy by the exogenous administration of estradiol dipropionate (EDP) was investigated in cyclic Microminipigs (MMpigs) and the effects of exogenous administration of prostaglandin (PG) F-2 alpha on estrus exhibition were assessed in pseudopregnant MMpigs. In experiment 1, ovariectomized MMpigs were given a single intramuscular injection of 0.5, 1.5, or 2.5 mg of EDP. The estradiol-17 beta level at each of these doses was significantly higher 1 to 3 days after EDP administration than on the day of the injection. In experiment 2, animals were given 1.5 mg of EDP once at 9 to 12 days after the end of estrus (D0) and then no (1.5 mg x 1 group), one (D0 and D4; 1.5 mg x 2 group), or two (D0, D4 and D7; 1.5 mg x 3 group) additional treatments. The pseudopregnancy rate was significantly higher in the 1.5 mg x 3 than in the 1.5 mg x 1 group. In experiment 3, PGF(2 alpha) was administered twice between 26 and 28 days after EDP treatment to five pseudopregnant gilts with a 24-h interval between the two injections. Estrus after PGF(2 alpha) treatment and LH surge were observed in 100% and 80% pseudopregnant MMpigs, respectively. The interval from the day of the first PGF(2 alpha) treatment to the onset of estrus was 6.5 +/- 0.2 days. These results indicate that multiple EDP treatments are required for induction of pseudopregnancy in MMpigs and estrus exhibition can be controlled in MMpigs by treatment with EDP and PGF(2 alpha).

DOI： 10.1262/jrd.2015-169

Takuya Yoshimura, Taiji Hamada, Hiroshi Hijioka, Masakazu Souda, Kazuhito Hatanaka, Takako Yoshioka, Sohsuke Yamada, Masato Tsutsui, Yoshihisa Umekita, Norifumi Nakamura, Akihide Tanimoto . PCP4/PEP19 promotes migration, invasion and adhesion in human breast cancer MCF-7 and T47D cells . ONCOTARGET7 ( 31 ) 49065 - 49074 2016.8Reviewed International journal

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

Purkinje cell protein (PCP) 4/peptide (PEP) 19 is expressed in Purkinje cells where it has a calmodulin-binding, anti-apoptotic function. We recently demonstrated that PCP4/PEP19 is expressed and inhibit apoptosis in human breast cancer cell lines. In the present study we investigated the role of PCP4/PEP19 in cell morphology, adhesion, migration, and invasion in MCF-7 and T47D human breast cancer cell lines. Knockdown of PCP4/PEP19 reduced the formation of filopodia-like cytoplasmic structures and vinculin expression, and enhanced E-cadherin expression. Activities of migration, invasion, and cell adhesion were also decreased after the knockdown of PCP4/PEP19 in MCF-7 and T47D cells. These results suggested that PCP4/PEP19 promotes cancer cell adhesion, migration, and invasion and that PCP4/PEP19 may be a potential target for therapeutic agents in breast cancer treatment which act by inhibiting epithelial-mesenchymal transition and enhancing apoptotic cell death.

DOI： 10.18632/oncotarget.7529

Sohsuke Yamada, Aya Nawata, Manabu Yoshioka, Tsubasa Hiraki, Michiyo Higashi, Kazuhito Hatanaka, Akihide Tanimoto . Complete regression of primary cutaneous malignant melanoma associated with distant lymph node metastasis: A teaching case mimicking blue nevus . BMC Research Notes9 ( 1 ) 366 - 366 2016.7Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：BioMed Central Ltd.

Background: Malignant melanoma (MM) tends to be spontaneously regressed, however, complete regression of primary cutaneous MM is an extremely rare phenomenon. Our aim is to be aware that pathologists and/or dermatologists can readily misinterpret it as the other benign or malignant lesions. Case presentation: A gradually growing and verrucous hypopigmented macule had been noticed in the right sole of a 65-year-old Japanese male since 2 years before, and it turned to be a solitary bluish to black patch with surrounding depigmentation and was recently decreased in size. In parallel, the patient had a rapidly growing black-pigmented mass lesion at the right inguen. The cutaneous specimen from the sole showed an aggregation of many melanophages predominantly in the middle to deep layer of dermis, associated with surrounding fibrosis, reactive vascular proliferation and CD8-positive T-lymphocytic infiltrate, covered by attenuated epidermis with absence of rete ridge. However, no remnant MM cells were completely seen in the step-serial sections. We first interpreted it as blue nevus. By contrast, the inguinal mass revealed a diffuse proliferation of highly atypical mono- to multi-nucleated large cells having abundant eosinophilic cytoplasm in the enlarged lymph node tissue. Immunohistochemical findings demonstrated that these atypical cells were specifically positive for HMB45 and Melan A. Therefore, we finally made a diagnosis of complete regression of primary cutaneous MM associated with distant lymph node metastasis of MM. Conclusion: Careful, not only general/cutaneous but histopathological, examinations should be necessary and adjunctive aids for reaching the correct diagnosis of complete regression of cutaneous MM.

DOI： 10.1186/s13104-016-2174-4

Seiya Yokoyama, Michiyo Higashi, Sho Kitamoto, Monika Oeldorf, Uwe Knippschild, Marko Kornmann, Kosei Maemura, Hiroshi Kurahara, Edwin Wiest, Tomofumi Hamada, Ikumi Kitazono, Yuko Goto, Takashi Tasaki, Tsubasa Hiraki, Kazuhito Hatanaka, Yuko Mataki, Hiroki Taguchi, Shinichi Hashimoto, Surinder K. Batra, Akihide Tanimoto, Suguru Yonezawa, Michael A. Hollingsworth . Aberrant methylation of MUC1 and MUC4 promoters are potential prognostic biomarkers for pancreatic ductal adenocarcinomas . ONCOTARGET7 ( 27 ) 42553 - 42565 2016.7Reviewed International journal

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

Pancreatic cancer is still a disease of high mortality despite availability of diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic neoplasms. MUC1 and MUC4 are high molecular weight transmembrane mucins. These are overexpressed in many carcinomas, and high expression of these molecules is a risk factor associated with poor prognosis. We evaluated the methylation status of MUC1 and MUC4 promoter regions in pancreatic tissue samples from 169 patients with various pancreatic lesions by the methylation specific electrophoresis (MSE) method. These results were compared with expression of MUC1 and MUC4, several DNA methylation/demethylation factors (e.g. ten-eleven translocation or TET, and activation-induced cytidine deaminase or AID) and CAIX (carbonic anhydrase IX, as a hypoxia biomarker). These results were also analyzed with clinicopathological features including time of overall survival of PDAC patients. We show that the DNA methylation status of the promoters of MUC1 and MUC4 in pancreatic tissue correlates with the expression of MUC1 and MUC4 mRNA. In addition, the expression of several DNA methylation/demethylation factors show a significant correlation with MUC1 and MUC4 methylation status. Furthermore, CAIX expression significantly correlates with the expression of MUC1 and MUC4. Interestingly, our results indicate that low methylation of MUC1 and/or MUC4 promoters correlates with decreased overall survival. This is the first report to show a relationship between MUC1 and/or MUC4 methylation status and prognosis. Analysis of epigenetic changes in mucin genes may be of diagnostic utility and one of the prognostic predictors for patients with PDAC.

DOI： 10.18632/oncotarget.9924

Sohsuke Yamada, Xin Guo, Ke-Yong Wang, Akihide Tanimoto, Yasuyuki Sasaguri . Novel function of histamine signaling via histamine receptors in cholesterol and bile acid metabolism: Histamine H2 receptor protects against nonalcoholic fatty liver disease . PATHOLOGY INTERNATIONAL66 ( 7 ) 376 - 385 2016.7Reviewed International journal

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

We have reported that the function of histamine and its receptors (HRs) has a close relationship with the development of nonalcoholic fatty liver disease (NAFLD). However, much less is known regarding its pathogenic and molecular mechanism (s), including the early stage of hepatic and intestinal function for lipid and bile acid (BA) metabolism. We used H1R and H2R knockout mice (H1/2R-KO) to clarify those pivotal roles in cholesterol/BA metabolism, in which H1/2R-KO mice were separately fed a short-term 1% cholesterol or cholic acid (CA) diet. [H-3]Cholesterol absorption study revealed that significantly enhanced accumulation occurred in the jejunum, blood and liver, but not in the feces, of H2R-KO mice, compared to wild-type and H1R-KO mice. Furthermore, four weeks after the high-cholesterol diet, the H2R-KO jejunum but not liver exhibited increased expressions of cholesterol transporters, consistent with higher plasma lipoprotein levels. Five days after CA diet, the H2R-KO mice showed significantly higher expressions of ileal BA-reabsorption and hepatic BA-efflux factors, corresponding to higher serum but lower fecal BA levels. The following long-term CA diets resulted in severe injury to the H2R-KOliver. Histamine/H2R signaling might have a protective role in the initial phase during NAFLD progression, correlated with cholesterol and BA metabolism in the liver/intestine.

DOI： 10.1111/pin.12423

窪田恵美, 西田ゆかり, 竹下かおり, 田中和彦, 平木翼, 義岡孝子, 東美智代, 畑中一仁, 谷本昭英 . 右側胸壁に発生した明細胞肉腫の1例 . 日本臨床細胞学会九州連合会雑誌47 69 - 72 2016.7Reviewed

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

背景:明細胞肉腫は軟部悪性黒色腫とも呼ばれ、若年成人に多く、四肢の遠位部に好発する。今回、稀な右胸壁発生の明細胞肉腫を経験したので報告する。症例:30代、女性。半年前より背部痛があり、右胸壁に増大傾向のある腫瘤を認めた。穿刺吸引細胞診では、比較的きれいな背景に、N/C比の高い類円形から紡錐形の細胞が散在性から小集塊状にみられた。細胞は類円形ないし円形核を有し、核小体は明瞭で微細顆粒状のクロマチン増量を認めた。明細胞肉腫、悪性末梢神経腫瘍、滑膜肉腫などが疑われたが組織型の推定は困難であった。摘出された腫瘍は、組織学的に淡明から弱好酸性の胞体および核小体明瞭な類円形核を有する腫瘍細胞のシート状充実性増殖からなり、メラニン色素は認められなかった。免疫組織化学ではHMB-45及びS-100蛋白が陽性であった。遺伝子検索は行っていないが、細胞所見、免疫組織化学を含む組織所見および臨床情報より明細胞肉腫と診断した。結論:明細胞肉腫の細胞像ではメラニン色素や明瞭な核小体に着目することが重要と考えられるが、メラニン色素が認められない場合には遺伝子解析とともに既往歴や発生部位などの臨床情報が鑑別に重要である。(著者抄録)

馬場淳徳, 北山香澄, 朝倉哲郎, 瀬筒秀樹, 谷本昭英, 金蔵拓郎 . 研究最前線シルクフィブロインを用いた新規創傷被覆材の開発 . 西日本皮膚科78 ( 3 ) 288 - 289 2016.6Reviewed

Aya Nawata, Hirotsugu Noguchi, Yuichi Mazaki, Toshihiro Kurahashi, Hiroto Izumi, Ke-Yong Wang, Xin Guo, Hidetaka Uramoto, Kimitoshi Kohno, Hatsumi Taniguchi, Yoshiya Tanaka, Junichi Fujii, Yasuyuki Sasaguri, Akihide Tanimoto, Toshiyuki Nakayama, Sohsuke Yamada . Overexpression of Peroxiredoxin 4 Affects Intestinal Function in a Dietary Mouse Model of Nonalcoholic Fatty Liver Disease . PLOS ONE11 ( 4 ) e0152549 2016.4Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：PUBLIC LIBRARY SCIENCE

Background
Accumulating evidence has shown that methionine- and choline-deficient high fat (MCD+HF) diet induces the development of nonalcoholic fatty liver disease (NAFLD), in which elevated reactive oxygen species play a crucial role. We have reported that peroxiredoxin 4 (PRDX4), a unique secretory member of the PRDX antioxidant family, protects against NAFLD progression. However, the detailed mechanism and potential effects on the intestinal function still remain unclear.
Methods & Results
Two weeks after feeding mice a MCD+HF diet, the livers of human PRDX4 transgenic (Tg) mice exhibited significant suppression in the development of NAFLD compared with wildtype (WT) mice. The serum thiobarbituric acid reactive substances levels were significantly lower in Tg mice. In contrast, the Tg small intestine with PRDX4 overexpression showed more suppressed shortening of total length and villi height, and more accumulation of lipid in the jejunum, along with lower levels of dihydroethidium binding. The enterocytes exhibited fewer apoptotic but more proliferating cells, and inflammation was reduced in the mucosa. Furthermore, the small intestine of Tg mice had significantly higher expression of cholesterol absorption-regulatory factors, including liver X receptor-alpha, but lower expression of microsomal triglyceride-transfer protein.
Conclusion
Our present data provide the first evidence of the beneficial effects of PRDX4 on intestinal function in the reduction of the severity of NAFLD, by ameliorating oxidative stress-induced local and systemic injury. We can suggest that both liver and intestine are spared, to some degree, by the antioxidant properties of PRDX4.

DOI： 10.1371/journal.pone.0152549

Tsubasa Hiraki, Yuko Goto, Ikumi Kitazono, Takashi Tasaki, Michiyo Higashi, Kazuhito Hatanaka, Akihide Tanimoto . The First Case of Pulmonary Alveolar Proteinosis With Small Cell Lung Carcinoma . INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY24 ( 2 ) 135 - 138 2016.4Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE PUBLICATIONS INC

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterized by alveolar accumulation of surfactant lipids and proteins. It is usually autoimmune and secondary to hematologic malignancy or infection. To date, only 5 case reports of PAP associated with lung cancers, including 2 cases of squamous cell carcinoma and 3 cases of adenocarcinoma, have been published. To the best of our knowledge, no case of PAP with small cell lung carcinoma has been reported thus far. We herein report the first case of PAP associated with small cell lung carcinoma.

DOI： 10.1177/1066896915614893

Satoru Morishita, Hiroaki Kawaguchi, Tomoji Ono, Naoki Miura, Michiaki Murakoshi, Keikichi Sugiyama, Hisanori Kato, Akihide Tanimoto, Hoyoku Nishino . Enteric lactoferrin attenuates the development of high-fat and high-cholesterol diet-induced hypercholesterolemia and atherosclerosis in Microminipigs . BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY80 ( 2 ) 295 - 303 2016.2Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS LTD

Previously, we found that enteric lactoferrin (eLF) could reduce the visceral fat accumulation known to associate strongly with metabolic syndrome symptoms and consequently with an increased risk of atherosclerosis. In this study, the atherosclerosis-preventive potential of LF was assessed in a high-fat and high-cholesterol diet (HFCD)-induced hypercholesterolemia and atherosclerosis model using Microminipig. Eight-week orally administered eLF remarkably reduced the HFCD-induced serum total and low-density lipoprotein cholesterol levels but not high-density lipoprotein cholesterol levels. A histological analysis of 15 arteries revealed that eLF systemically inhibited the development of atherosclerotic lesions. Pathway analysis using identified genes that characterized eLF administration in liver revealed significant changes in the steroid biosynthesis pathway (ssc00100) and all affected genes in this pathway were upregulated, suggesting that cholesterol synthesis inhibited by HFCD was recovered by eLF. In summary, eLF could potentially prevent the hypercholesterolemia and atherosclerosis through protecting homeostasis from HFCD-induced dysfunction of cholesterol metabolism.

DOI： 10.1080/09168451.2015.1091713

Yoshinobu Saitoh, Takao Setoguchi, Masahito Nagata, Arisa Tsuru, Shunsuke Nakamura, Satoshi Nagano, Yasuhiro Ishidou, Hiroko Nagao-Kitamoto, Masahiro Yokouchi, Shingo Maeda, Akihide Tanimoto, Tatsuhiko Furukawa, Setsuro Komiya . Combination of Hedgehog inhibitors and standard anticancer agents synergistically prevent osteosarcoma growth . INTERNATIONAL JOURNAL OF ONCOLOGY48 ( 1 ) 235 - 242 2016.1Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

High-dose chemotherapy and surgical intervention have improved long-term prognosis for non-metastatic osteosarcoma to 50-80%. However, metastatic osteosarcoma exhibits resistance to standard chemotherapy. We and others have investigated the function of Hedgehog pathway in osteosarcoma. To apply our previous findings in clinical settings, we examined the effects of Hedgehog inhibitors including arsenic trioxide (ATO) and vismodegib combined with standard anticancer agents. We performed WST-1 assays using ATO, cisplatin (CDDP), ifosfamide (IFO), doxorubicin (DOX), and vismodegib. Combination-index (CI) was used to examine synergism using CalcuSyn software. Xenograft models were used to examine the synergism in vivo. WST-1 assays showed that 143B and Saos2 cell proliferation was inhibited by ATO combined with CDDP, IFO, DOX, and vismodegib. Combination of ATO and CDDP, IFO, DOX or vismodegib was synergistic when the two compounds were used on proliferating 143B and Saos2 human osteosarcoma cells. An osteosarcoma xenograft model showed that treatment with ATO and CDDP, IFO, or vismodegib significantly prevented osteosarcoma growth in vivo compared with vehicle treatment. Our findings indicate that combination of Hedgehog pathway inhibitors and standard FDA-approved anticancer agents with established safety for human use may be an attractive therapeutic method for treating osteosarcoma.

DOI： 10.3892/ijo.2015.3236

Sohsuke Yamada, Yoshikazu Harada, Hirotsugu Noguchi, Naoko Satoh, Satoshi Kimura, Toshiyuki Nakayama, Akihide Tanimoto . Embryonal rhabdomyosarcoma arising from the uterine corpus in a postmenopausal female: a surgical case challenging the genuine diagnosis on a cytology specimen . DIAGNOSTIC PATHOLOGY11 3 - 3 2016.1Reviewed International journal

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

A 55-year-old postmenopausal female presented with genital bleeding and lower abdominal mass. An abdominal MRI revealed a heterogeneously enhanced, 15 x 10 cm mass, completely filling the lumen of the enlarged uterus. The cytologic analysis of the mass showed tumor cells in small clusters and as individual cells showing hyperchromatic round to oval nuclei, and pleomorphic and occasionally unipolar "tadpole"-shaped cytoplasm, in a background of severe necrosis and many degenerated squamous cells. We first interpreted it merely as atypical cells, possibly originated from sarcoma. A total abdominal hysterectomy and salpingo-oophorectomy were performed, and gross examination showed an exophytic polypoid mass with a whitish to white-grayish, necrotic appearance, protruding from the endometrial mucosa. Microscopically, the tumor was composed of a diffuse proliferation of highly atypical spindle-shaped cells, admixed with many characteristic rhabdomyoblasts having abundant densely eosinophilic cytoplasm with sometimes distinct cross-striations, coexisted with cellular primitive small blue round to oval cells foci. However, neither carcinoma nor additional heterologous sarcoma components were completely seen within our thorough investigation. Therefore, we finally made a diagnosis of embryonal rhabdomyosarcoma arising from the uterine corpus. We should be aware that owing to its characteristic features, cytopathologists might be able to determine a genuine diagnosis, based on multiple and adequate cytology samplings.

DOI： 10.1186/s13000-016-0451-0

Takao Setoguchi, Hirotaka Kawakami, Yasuhiro Ishidou, Hideki Kawamura, Junichiro Nishi, Takako Yoshioka, Hironori Kakoi, Satoshi Nagano, Masahiro Yokouchi, Akihide Tanimoto, Setsuro Komiya . Cut-off values of latent infection in patients with rapid migration following bipolar hip hemiarthroplasty . BMC MUSCULOSKELETAL DISORDERS17 37 - 37 2016.1Reviewed International journal

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

Background: Although most patients achieve favorable results following bipolar hip hemiarthroplasty (BHA), some experience rapid migration of the prosthesis. We retrospectively reviewed 18 patients with BHA that necessitated revision.
Methods: We examined soft tissues obtained from periprosthetic lesions. In total, 18 patients with pain and acetabular migration of the BHA prosthesis were included. The patients were divided into a polymorphonuclear leukocyte (PMN)-positive (>= 5 PMNs per high-power field [HPF]) and PMN-negative (< 5 PMNs/HPF) group.
Results: Pathological findings showed that 11 patients were PMN-positive, which was indicative of infection. All patients in the PMN-positive group showed no polyethylene particles or foreign body giant cells, while all patients in the PMN-negative group showed polyethylene debris or foreign body giant cells (p < 0.001). BHA survival, C-reactive protein (CRP) levels, and the Japanese Orthopaedic Association (JOA) hip score were significantly different between the PMN-positive and PMN-negative group (p < 0.01). A BHA survival cut-off value of 3270 days was diagnostic for PMN positivity (sensitivity: 100 %; specificity: 100 %). The cut-off values for CRP and the JOA hip score were 0.43 mg/dl and 56 points, respectively. Four of 11 PMN-positive patients showed no clinical symptoms of infection (asymptomatic PMN-positive group). BHA survival, CRP levels, and JOA hip scores were significantly different between the asymptomatic PMN-positive and PMN-negative group (p < 0.05). A BHA survival cut-off of 3270 days was diagnostic for asymptomatic PMN positivity (sensitivity: 100 %; specificity: 100 %). The cut-off values for CRP and the JOA hip score were 0.43 mg/dl and 57 points, respectively.
Conclusion: Our findings suggest that some portion of rapid BHA prosthesis migration is caused by mild infection. Careful pathological examination should be performed to identify infection before removal of the BHA prosthesis in patients who develop migration within 9 years.

DOI： 10.1186/s12891-016-0876-3

Yoshimura T, Yamada S, Shima K, Nakamura N, Tanimoto A . An elastofibromatous lesion at the tip of the sublingual fold . J Dent & Oral Disord2 ( 6 ) 1031 2016Reviewed

Hirofumi Shimada, Miguel Otero, Kaneyuki Tsuchimochi, Satoshi Yamasaki, Harutoshi Sakakima, Fumiyo Matsuda, Megumi Sakasegawa, Takao Setoguchi, Lin Xu, Mary B. Goldring, Akihide Tanimoto, Setsuro Komiya, Kosei Ijiri . CCAAT/enhancer binding protein beta (C/EBP beta) regulates the transcription of growth arrest and DNA damage-inducible protein 45 beta (GADD45 beta) in articular chondrocytes . PATHOLOGY RESEARCH AND PRACTICE212 ( 4 ) 302 - 309 2016Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER GMBH, URBAN & FISCHER VERLAG

Osteoarthritis (OA) is a whole joint disease characterized by cartilage degradation, which causes pain and disability in older adults. Our previous work showed that growth arrest and DNA damage-inducible protein 45 beta (GADD45 beta) is upregulated in chondrocyte clusters in OA cartilage, especially in the early stage of this disease. CCAAT/enhancer binding protein beta (C/EBP beta) is expressed in the hypertrophic growth plate chondrocytes and functions in synergy with GADD45 beta. Here, the presence and localization of these proteins was assessed by immunohistochemistry using articular cartilage from OA patients, revealing colocalization of C/EBP beta and GADD45 beta in OA chondrocytes. GADD45 beta promoter analysis was performed to determine whether C/EBP beta directly regulates GADD45 beta transcription. Furthermore, we analyzed the effect of C/EBP beta on Gadd45 beta gene regulation in articular chondrocytes in vivo and in vitro. Immunohistochemical analysis of C/ebp beta-haploinsufficient mice (C/ebp beta(+/-)) cartilage showed that C/ebp beta haploinsufficiency led to reduced Gadd45 beta gene expression in these cells. In vitro, we evaluated the effects of conditional C/EB1 beta overexpression driven by the cartilage oligomeric matrix protein (Comp) promoter in mComp-tTA;pTRE-Tight-BI-DsRed-mC/ebp beta transgenic mice. C/EBP beta overexpression significantly stimulated Gadd45 beta gene expression in articular chondrocytes. Taken together, our data demonstrate that C/EBPP plays a central role in controlling Gadd45 beta gene expression in these cells. (C) 2016 The Authors. Published by Elsevier GmbH.

DOI： 10.1016/j.prp.2016.01.009

KAWAGUCHI Hiroaki, HORIUCHI Masahisa, TANIMOTO Akihide . Toxicologic pathology of Microminipig . Annual Meeting of the Japanese Society of Toxicology43 S9 - 3 2016Reviewed

北薗育美, 東美智代, 平木翼, 後藤優子, 田崎貴嗣, 義岡孝子, 畑中一仁, 藤尾信吾, 平野宏文, 有田和徳, 谷本昭英 . 第三脳室脊索腫様膠腫の1例 . 診断病理32 ( 4 ) 285 - 288 2015.10Reviewed

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

第三脳室脊索腫様膠腫の1例を報告する。症例は44歳女性。12年前に無月経、頭痛があり精査。第三脳室内腫瘤性病変を指摘され、生検されたが、炎症所見のみで確定診断には至らなかった。病変の増大を認めたため摘出された。組織学的に、粘液腫状基質や炎症細胞浸潤を伴った上皮様腫瘍細胞の増殖を認めた。免疫組織学的検討では腫瘍細胞はGFAP、Vimentinにびまん性に陽性でCD34に部分的に陽性、EMAに一部が弱陽性を示した。以上の所見から第三脳室脊索腫様膠腫と診断した。(著者抄録)

Arisa Tsuru, Takao Setoguchi, Naoya Kawabata, Masataka Hirotsu, Takuya Yamamoto, Satoshi Nagano, Masahiro Yokouchi, Hironori Kakoi, Hideki Kawamura, Yasuhiro Ishidou, Akihide Tanimoto, Setsuro Komiya . Enrichment of bacteria samples by centrifugation improves the diagnosis of orthopaedics-related infections via real-time PCR amplification of the bacterial methicillin-resistance gene . BMC Research Notes8 ( 1 ) 288 - 288 2015.7Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：BioMed Central Ltd.

Background: To effectively treat orthopaedic infections by methicillin-resistant strains, an early diagnosis is necessary. Bacterial cultures and real-time polymerase chain reaction (PCR) have been used to define methicillin-resistant staphylococci. However, even when patients display clinical signs of infections, bacterial culture and real-time PCR often cannot confirm infection. The aim of this study was to prospectively compare the utility of real-time PCR for the mecA gene detection following centrifugation of human samples with suspected orthopaedic infections. Results: In addition to the conventional real-time PCR method, we performed real-time PCR following centrifugation of the sample at 4,830xg for 10 min in a modified real-time PCR (M-PCR) method. We suspended cultured methicillin-resistant Staphylococcus aureus and generated standard dilution series for in vitro experiments. The in vitro detection sensitivity of the M-PCR method was approximately 5.06 times higher than that of the conventional real-time PCR method. We performed bacterial culture, pathological examination, real-time PCR, and M-PCR to examine the infectious fluids and tissues obtained from 36 surgical patients at our hospital. Of these, 20 patients who had undergone primary total hip arthroplasty were enrolled as negative controls. In addition, 15 patients were examined who were clinically confirmed to have an infection, including periprosthetic joint infection (eight patients), pyogenic spondylitis (two patients), infectious pseudoarthrosis (two patients), and after spine surgery (three patients). In one sample from a patient who developed infectious pseudoarthrosis and two samples from surgical site infections after spine surgery, the mecA gene was detected only by the M-PCR method. In one patient with infectious pseudoarthrosis, one patient with infection after arthroplasty, and two patients with purulent spondylitis, the detection sensitivity of the M-PCR method was increased compared with PCR (clinical sample average: 411.6 times). Conclusions: These findings suggest that the M-PCR method is useful to detect methicillin-resistant strains infections. In addition, the centrifugation process only takes 10 min longer than conventional real-time PCR methods. We believe that the M-PCR method could be clinically useful to detect orthopaedic infections caused by methicillin-resistant strains.

DOI： 10.1186/s13104-015-1180-2

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