Faculty Profiles - akihide Tanimoto

Atsushi Miyamoto, Md. Zahorul Islam, Hiroaki Kawaguchi, Naoki Miura, Emi Yamzaki-Himeno, Mitsuya Shiraishi, Noriaki Miyoshi, Akihide Tanimoto . Effect of continuous intravenous infusion of angiotensin II on Microminipig basilar arterial responsiveness . JOURNAL OF PHARMACOLOGICAL SCIENCES121 22P - 22P 2013Reviewed

谷本昭英, 川口博明 . 第三の家畜実験動物としてのミニブタブタの研究利用の現状 . 病理と臨床30 ( 11 ) 1276 - 1279 2012.11

Xin Guo, Sohsuke Yamada, Akihide Tanimoto, Yan Ding, Ke-Yong Wang, Shohei Shimajiri, Yoshitaka Murata, Satoshi Kimura, Takashi Tasaki, Atsunori Nabeshima, Teruo Watanabe, Kimitoshi Kohno, Yasuyuki Sasaguri . Overexpression of Peroxiredoxin 4 Attenuates Atherosclerosis in Apolipoprotein E Knockout Mice . ANTIOXIDANTS & REDOX SIGNALING17 ( 10 ) 1362 - 1375 2012.11Reviewed International journal

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

Aim: A growing body of evidence has shown that increased formation of oxidized molecules and reactive oxygen species within the vasculature (i.e., the extracellular space) plays a crucial role in the initiation and progression of atherosclerosis and in the formation of unstable plaques. Peroxiredoxin 4 (PRDX4) is the only known secretory member of the antioxidant PRDX family. However, the relationship between PRDX4 and susceptibility to atherosclerosis has remained unclear. Results: To define the role of PRDX4 in hyperlipidemia-induced atherosclerosis, we generated hPRDX4 transgenic (Tg) and apolipoprotein E (apoE) knockout mice (hPRDX4(+/+)/apoE(-/-)). After feeding the mice a high-cholesterol diet, they showed fewer atheromatous plaques, less T-lymphocyte infiltration, lower levels of oxidative stress markers, less necrosis, a larger number of smooth muscle cells, and a larger amount of collagen, resulting in thickened fibrous cap formation and possible stable plaque phenotype as compared with apoE(-/-) mice. We also detected greater suppression of apoptosis and decreased Bax expression in hPRDX4(+/+)/apoE(-/-) mice than in apoE(-/-) mice. Bone marrow transplantation from hPRDX4(+/+) donors to apoE(-/-) mice confirmed the antiatherogenic aspects of PRDX4, revealing significantly suppressed atherosclerotic progression. Innovation: In this study, we demonstrated for the first time that PRDX4 suppressed the development of atherosclerosis in apoE(-/-) mice fed a high-cholesterol diet. Conclusion: These data indicate that PRDX4 is an antiatherogenic factor and, by suppressing oxidative damage and apoptosis, that it may protect against the formation of vulnerable (unstable) plaques. Antioxid. Redox Signal. 17, 1362-1375.

DOI： 10.1089/ars.2012.4549

Satoshi Kimura, Akihide Tanimoto, Ke-Yong Wang, Shohei Shimajiri, Xin Guo, Takashi Tasaki, Sohsuke Yamada, Yasuyuki Sasaguri . Expression of macrophage-derived chemokine (CCL22) in atherosclerosis and regulation by histamine via the H2 receptor . PATHOLOGY INTERNATIONAL62 ( 10 ) 675 - 683 2012.10Reviewed International journal

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

Macrophage-derived chemokine (CCL22) is a member of the CC-family of chemokines and is synthesized by monocyte-derived macrophages and dendritic cells (DCs). In this study, we investigate the relationship between monocytes/macrophages and histamine in atherosclerosis and discover that histamine levels regulate various immunologically important molecules and influences atherosclerotic progression. Immunohistochemical analysis of human atherosclerotic lesions revealed that macrophages and DCs express CCL22. The human acute monocytic leukemia cell line (THP-1) adhered to culture plates and morphologically changed to macrophage-like cells when treated with tetradecanoylphorbol-13-acetate (TPA). Macrophage-like cells derived from THP-1 cells and cultivated peripheral blood mononuclear cells (PBMCs) show similar expression of CCL22. Gene expression of CCL22 was also detected in THP-1 cells treated with histamine and the expression of the protein produced by the CCL22 gene is similar in PBMCs and THP-1 cells. In addition, the histamine H2 receptor mediated these reactions. Our results suggest that CCL22 expression in monocytes is regulated by histamine, and that CCL22 is involved centrally in the development of human atherosclerotic lesions. In conclusion, CCL22 is a marker that is a characteristic of the monocytes/ macrophages migrating into atherosclerotic lesions and histamine plays a role in regulating its expression.

DOI： 10.1111/j.1440-1827.2012.02854.x

Y. Ohi, Y. Umekita, Y. Sagara, Y. Rai, D. Yotsumoto, A. Matsukata, S. Baba, S. Tamada, Y. Matsuyama, M. Ando, Y. Sagara, M. Sasaki, S. Tsuchimochi, A. Tanimoto, Y. Sagara . Whole sentinel lymph node analysis by a molecular assay predicts axillary node status in breast cancer . BRITISH JOURNAL OF CANCER107 ( 8 ) 1239 - 1243 2012.10Reviewed

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

BACKGROUND: The one-step nucleic acid amplification (OSNA) assay is a rapid procedure for the detection of lymph node (LN) metastases using molecular biological techniques. The aim of this study was to assess the reliability of the whole sentinel lymph node (SLN) analysis by the OSNA assay as a predictor of non-SLN metastases.
METHODS: Consecutive 742 patients with breast cancer were enroled in the study. The association of non-SLN or >= 4 LN metastases with clinicopathological variables was investigated using multivariate logistic analysis.
RESULTS: In total, 130 patients with a positive SLN who underwent complete axillary LN dissection were investigated. The frequency of non-SLN metastases in patients who were OSNA+ and + + was 19.3% and 53.4%, respectively, and that in patients with >= 4 LN metastases who were OSNA+ and + + was 7.0% and 27.4%, respectively. The cytokeratin 19 (CK19) mRNA copy number (>= 5.0 x 10(3); OSNA+ +) in the SLN was the most significant predictors of non-SLN metastases (P = 0.003). The CK19 mRNA copy number (>= 1.0 x 10(5)) in the SLN was the only independent predictor of >= 4 LN metastases (P = 0.014).
CONCLUSION: Whole SLN analysis using the OSNA assay could become a valuable method for predicting non-SLN and >= 4 LN metastases. British Journal of Cancer (2012) 107, 1239-1243. doi:10.1038/bjc.2012.387 www.bjcancer.com Published online 28 August 2012 (C) 2012 Cancer Research UK

DOI： 10.1038/bjc.2012.387

Sohsuke Yamada, Akihide Tanimoto, Atsunori Nabeshima, Takashi Tasaki, Ke-Yong Wang, Shohei Kitada, Hirotsugu Noguchi, Yasuyuki Sasaguri . Diffuse large B-cell lymphoma presenting with neurolymphomatosis and intravascular lymphoma: a unique autopsy case with diverse neurological symptoms . DIAGNOSTIC PATHOLOGY7 94 - 94 2012.8Reviewed International journal

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

A 78-year-old Japanese male noticed a difficulty in the beginning of standing up, followed by 7a progressive numbness of extremities with pain, Bell's palsy, dysarthria, and difficulty in swallowing. A clinician had suspected cancer of unknown primary origin, accompanied by the diverse and elusive neurological symptoms, likely presenting as painful mononeuropathy simplex and cranial neuropathy. He developed dysbasia over weeks and died 1 month after the symptom onset. At autopsy, an ill-defined large and soft tumor mass in the right lobe of the liver with direct invasion into the right adrenal gland was observed. The left adrenal gland or right iliopsoas muscle was also involved. Microscopic findings showed a monotonous proliferation of medium-sized to large atypical lymphoid cells, which were diffusely positive for CD20 in immunohistochemistry, consistent with diffuse large B-cell lymphoma (DLBL). Furthermore, the lymphoma cells aggressively infiltrated endoneurial and subperineurial spaces not only in the peripheral nerves and plexuses, but partly in the spinal nerve roots, and intravascular spaces in various tissues. Therefore, systemic lymphoma (DLBL) complicated with neurolymphomatosis (NL) and intravascular lymphoma (IVL) was diagnosed. Very early diagnosis and treatment are necessary for the NL patients with poor prognosis.

DOI： 10.1186/1746-1596-7-94

Emiko Haruyama, Yuki Ayukawa, Koshiro Kamura, Megumi Mizutamari, Yojiro Ooshima, Akihide Tanimoto . Morphometric Examination for Development of Reproductive Organs in Male Cynomolgus Monkeys . TOXICOLOGIC PATHOLOGY40 ( 6 ) 918 - 925 2012.8Reviewed International journal

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

We previously reported on a histological classification of cynomolgus monkey testis into six grades (1, immature; 2, prepuberty; 3, onset of puberty; 4, puberty; 5, early adult; 6, adult) based on spermatogenesis development. In this investigation, the accessory reproductive organs from the same animals underwent histomorphometric examination, in addition to being examined histologically and weighed, to evaluate relationships between these parameters and the six grades. Seminiferous tubule diameter increased corresponding to the testicular maturity grade and was notably increased at grade 6. Beginning from grade 3, increases in the areas of the ductus epididymis were noted, and reserved sperm was visible in the lumen. In the prostate, the glandular lumen area per unit area showed an increase beginning from grade 3 but no clear differences between grades 4 and 6; advanced development of epithelial height was observed at grade 6. In the seminal vesicle, development of the epithelial cell layer was markedly increased at grade 6. It was concluded that development of the male accessory reproductive organs began after reserved sperm was observed in the lumen of the ductus epididymis (grade 3) and that these organs were developed notably when the testis reached sexual maturity (grade 6).

DOI： 10.1177/0192623312444620

永尾聡子, 前田ゆかり, 久木田妙子, 皆倉愛美, 梅北善久, 谷本昭英, 大井恭代 . 神経内分泌への分化を示す非浸潤性乳管癌の細胞診断 . 日本臨床細胞学会九州連合会雑誌43 51 - 56 2012.8Reviewed

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

目的:神経内分泌への分化を示す非浸潤性乳管癌(Neuroendocrine ductal carcinoma in situ:NE-DCIS)の臨床所見と細胞像を明らかにする。方法:細胞診が行われたNE-DCIS 3例の臨床所見と細胞所見について検討を行った。成績:臨床所見では血性乳頭分泌を認めた(3/3例)。細胞所見は、出血性背景に多数の乳管上皮細胞が出現しており、充実性あるいは結合性に乏しい大小の重積集塊で、発達した血管を伴っていた(3/3例)。核は偏在性で緊満感があり均一であったが(3/3例)、一部に核形不整を認めた(1/3例)。細胞質はライトグリーン好染性で一部細顆粒状を示し、孤立細胞は明瞭な細胞質を有していた(3/3例)。診断は悪性で(3/3例)、組織推定はDCIS(2/3例)、充実腺管癌(1/3例)であった。結論:NE-DCISは細胞学的に特徴的な所見を示し、臨床所見なども考慮すれば、NE-DCISを推定病変として挙げることは可能であると思われた。(著者抄録)

Emiko Haruyama, Masakazu Suda, Yuki Ayukawa, Koshiro Kamura, Megumi Mizutamari, Yojiro Ooshima, Akihide Tanimoto . Testicular Development in Cynomolgus Monkeys . TOXICOLOGIC PATHOLOGY40 ( 6 ) 935 - 942 2012.8Reviewed International journal

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

The testes from 136 male cynomolgus monkeys were examined histopathologically in order to investigate the relationship between the development of spermatogenesis and testis weight, age, and body weight. At Grade 1 (immature), Sertoli cells and spermatogonia were the only cell classes in the testis. At Grade 2 (pre-puberty), no elongated spermatids were observed in the testis, although a few round spermatids and small lumen formation were observed. At Grade 3 (onset of puberty), all classes of germ cells were observed in the testis, although seminiferous tubule diameters and numbers of germ cells were small. Slight debris in the epididymis was observed in almost all animals. At Grade 4 (puberty), almost complete spermatogenesis was observed in the seminiferous tubules and it was possible to ascertain the spermatogenesis stage as described by Clermont, although tubule diameters and numbers of germ cells were small. There was less debris in the epididymis than at Grade 3. At Grade 5 (early adult), complete spermatogenesis was observed in the seminiferous tubules. At Grade 6 (adult), complete spermatogenesis in the seminiferous tubules and a moderate or large number of sperm in the epididymis were observed. Moreover, sperm analysis using ejaculated sperm was possible. Logistic regression analysis showed that testis weight is a good indicator of testicular maturity.

DOI： 10.1177/0192623312444619

Hiroaki Kawaguchi, Tomonobu Yamada, Naoki Miura, Yoshihiro Takahashi, Tsuyoshi Yoshikawa, Hiroyuki Izumi, Tatsuo Kawarasaki, Noriaki Miyoshi, Akihide Tanimoto . Reference Values of Hematological and Biochemical Parameters for the World Smallest Microminipigs . JOURNAL OF VETERINARY MEDICAL SCIENCE74 ( 7 ) 933 - 936 2012.7Reviewed

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC VET SCI

In this study, we demonstrated growth curves and reference values for hematological and serum biochemical parameters of Microminipigs, the world smallest experimental minipigs. In both male and female animals, the body weights (BWs) at 3 and 6 months of age were <5 kg and <10 kg, respectively, and growth curve revealed almost plateau (approximately 20 kg BW) after 18 months of age. Major hematological and serum biochemical parameters showed no gender differences and the values were very similar to those in Gottingen and Yukatan minipigs. The values obtained in this study can serve as fundamental reference, and thereby facilitate the use of Microminipig in life science research.

DOI： 10.1292/jvms.11-0571

Satoshi Kimura, Akihide Tanimoto, Shohei Shimajiri, Takakazu Sasaguri, Sohsuke Yamada, Ke-Yong Wang, Xin Guo, Yasuyuki Sasaguri . Unilateral gynecomastia and pseudoangiomatous stromal hyperplasia in neurofibromatosis: case report and review of the literature. . Pathology, research and practice208 ( 5 ) 318 - 22 2012.5Reviewed International journal

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

In this article, we describe unilateral gynecomastia and pseudoangiomatous stromal hyperplasia (PASH) in a case of type-1 neurofibromatosis (NF-1). It is important to distinguish PASH from fibroadenoma clinically, and from true blood capillaries and angiosarcoma histologically. In the present case, giant multinucleated cells lined the pseudovascular spaces, which was markedly different from that of conventional breast PASH. The origin of PASH has been reported to be either the fibroblast or the myofibroblast phenotype and may be affected by endocrine signaling because many cases have been reported in premenopausal women, and cases are often estrogen (ER) and progesterone receptor (PR) positive. However, previous reports have identified PASH in NF-1 in juvenile males only, and the cases were negative for α-SMA, ER and PR. The cause and prognosis of PASH in NF-1 may be distinguished from that of conventional PASH, and mast cells, histiocytes and CD54 may play roles.

DOI： 10.1016/j.prp.2012.03.003