Faculty Profiles - ARIMA, Hiroshi

Papers - ARIMA, Hiroshi

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小林朋子, 岩間信太郎, 安田康紀, 岩田尚子, 椙村益久, 安藤雄一, 秋山真志, 長谷川好規, 有馬寛

日本内分泌学会雑誌 Vol. 93 ( Suppl.Update ) page： 70 - 72 2017.6

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(一社)日本内分泌学会

2016年6月時点において、当院で免疫チェックポイント阻害薬として抗CTLA-4抗体イピリムマブ(Ipi)が投与された12例および抗PD-1抗体ニボルマブ(Niv)が投与された23例を対象に、内分泌学的評価を行った。その結果、Ipi投与中の内分泌有害事象は下垂体炎が2件(16.7%)、低Na血症が2件(16.7%)、副腎炎が1件(8.3%)、TSH値異常が4件(33.3%)に認められた。Niv投与中の内分泌有害事象はTSH値異常が7件(35.0%)、破壊性甲状腺炎が1件(4.3%)、甲状腺自己抗体陽転化が1件(4.3%)に認められた。Ipi投与中に発生した下垂体炎は、2件とも前治療としてNivが投与されており、Niv治療歴のある場合にはIpiによる下垂体炎を特に注意する必要があると考えられた。また、当院で経験した重篤な破壊性甲状腺炎の経過から、Niv投与前に甲状腺自己抗体が陽性の場合には甲状腺障害の発症に注意が必要であると示唆された。

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J01160&link_issn=&doc_id=20170718400022&doc_link_id=10.1507%2Fendocrine.93.S.Update_70&url=https%3A%2F%2Fdoi.org%2F10.1507%2Fendocrine.93.S.Update_70&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

4-PBAは家族性中枢性尿崩症モデルマウスにおいて多尿の進行およびバソプレシンニューロンの細胞死を抑制する

橡谷昌佳, 萩原大輔, 宮田崇, 森下啓明, 有馬寛

日本内分泌学会雑誌 Vol. 93 ( 1 ) page： 263 - 263 2017.4

AVPニューロンのin vitro実験系の確立 AVP-Venusマウスを用いた検討

萩原大輔, 宮田崇, 橡谷昌佳, 森下啓明, 有馬寛

日本内分泌学会雑誌 Vol. 93 ( 1 ) page： 276 - 276 2017.4

ニボルマブによる甲状腺障害の臨床的特徴

小林朋子, 岩間信太郎, 安田康紀, 岩田尚子, 横田憲二, 椙村益久, 近藤征史, 安藤雄一, 秋山真志, 長谷川好規, 有馬寛

日本内分泌学会雑誌 Vol. 93 ( 1 ) page： 360 - 360 2017.4

抗ラブフィリン3A抗体の小児期発症リンパ球性漏斗下垂体後葉炎における診断的有用性に関する検討

岩田尚子, 岩間信太郎, 安田康紀, 椙村益久, 有馬寛

日本内分泌学会雑誌 Vol. 93 ( 1 ) page： 317 - 317 2017.4

ラブフィリン3A免疫マウスにおける視床下部下垂体後葉炎び病態の解析

安田康紀, 岩間信太郎, 岩田尚子, 椙村益久, 有馬寛

日本内分泌学会雑誌 Vol. 93 ( 1 ) page： 276 - 276 2017.4

疾患特異的iPS細胞を用いた家族性中枢性尿崩症の病態解明

光本一樹, 須賀英隆, 山田登美子, 加納麻弓子, 橡谷昌佳, 大曽根親文, 笠井貴敏, 萩原大輔, 有馬寛

日本内分泌学会雑誌 Vol. 93 ( 1 ) page： 276 - 276 2017.4

Effects of clozapine on adipokine secretions/productions and lipid droplets in 3T3-L1 adipocytes. Open Access

Tomomi Tsubai, Akira Yoshimi, Yoji Hamada, Makoto Nakao, Hiroshi Arima, Yutaka Oiso, Yukihiro Noda

Journal of pharmacological sciences Vol. 133 ( 2 ) page： 79 - 87 2017.2

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

Clozapine, a second-generation antipsychotic (SGA), is a cause of side effects related to metabolic syndrome. The participation of serotonin 5-HT2C and histamine H1 receptors in the central nervous system has been reported as a mechanism of the weight gain caused by clozapine. In the present study, we investigated the direct pharmacological action of clozapine on the 3T3-L1 adipocytes and compared it to that of blonanserin, an SGA with low affinity for both receptors. Short-term exposure to clozapine decreased secretion and mRNA expression of leptin. Long-term exposure decreased leptin as well as adiponectin secretion, and further increased lipid droplets accumulation. However, short- and long-term exposures to blonanserin did not affect these parameters. A selective serotonin 5-HT2C, but not a histamine H1, receptor antagonist enhanced the decreased secretion of leptin induced by short-term exposure to clozapine, but did not affect the increased accumulation of lipid droplets. Our findings indicate that clozapine, but not blonanserin, strongly and directly affected the secretion of adipokines, such as leptin, in adipocytes and caused adipocyte enlargement.

DOI： 10.1016/j.jphs.2017.01.004

Open Access

Web of Science

PubMed

Deficiency of PTP1B Attenuates Hypothalamic Inflammation via Activation of the JAK2-STAT3 Pathway in Microglia Open Access

Taku Tsunekawa, Ryoichi Banno, Akira Mizoguchi, Mariko Sugiyama, Takashi Tominaga, Takeshi Onoue, Daisuke Hagiwara, Yoshihiro Ito, Shintaro Iwama, Motomitsu Goto, Hidetaka Suga, Yoshihisa Sugimura, Hiroshi Arima

EBIOMEDICINE Vol. 16 page： 172 - 183 2017.2

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

Protein tyrosine phosphatase 1B (PTP1B) regulates leptin signaling in hypothalamic neurons via the JAK2-STAT3 pathway. PTP1B has also been implicated in the regulation of inflammation in the periphery. However, the role of PTP1B in hypothalamic inflammation, which is induced by a high-fat diet (HFD), remains to be elucidated. Here, we showed that STAT3 phosphorylation (p-STAT3) was increased in microglia in the hypothalamic arcuate nucleus of PTP1B knock-out mice (KO) on a HFD, accompanied by decreased Tnf and increased Il10 mRNA expression in the hypothalamus compared to wild-type mice (WT). In hypothalamic organotypic cultures, incubation with TNF alpha led to increased p-STAT3, accompanied by decreased Tnf and increased Il10 mRNA expression, in KO compared to WT. Incubation with p-STAT3 inhibitors or microglial depletion eliminated the differences in inflammation between genotypes. These data indicate an important role of JAK2-STAT3 signaling negatively regulated by PTP1B in microglia, which attenuates hypothalamic inflammation under HFD conditions. (C) 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

DOI： 10.1016/j.ebiom.2017.01.007

Open Access

Web of Science

PubMed

NMDA receptor antagonist prevents cell death in the hippocampal dentate gyrus induced by hyponatremia accompanying adrenal insufficiency in rats

Hisakazu Izumida, Hiroshi Takagi, Haruki Fujisawa, Naoko Iwata, Kohtaro Nakashima, Seiji Takeuchi, Shintaro Iwama, Takashi Namba, Yukio Komatu, Kozo Kaibuchi, Yutaka Oiso, Hiroshi Arima, Yoshihisa Sugimura

EXPERIMENTAL NEUROLOGY Vol. 287 ( Pt 1 ) page： 65 - 74 2017.1

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

Selective apoptosis of granule cells in the hippocampal dentate gyrus (DG) of rats with bilateral adrenalectomy (ADX) and in patients who died of adrenal insufficiency has been reported. Although adrenal insufficiency is a common disease and is usually associated with hyponatremia, its effect on the central nervous system and in apoptosis in the hippocampus remain to be elucidated. Using rat models to represent clinical hyponatremia accompanying adrenal insufficiency, we show that reduced serum [Na+] was associated with selective apoptosis in the DG. Nine days after ADX, apoptotic cells were observed in the DG of rats whose serum [Na+] was <125 mEq/L (moderate hyponatremia), but rarely in those whose serum [Na+] was 125 mEq/L or in normonatremic rats. Although all hyponatremic ADX rats survived following treatment with corticosterone and saline started 7 days after ADX when apoptosis had not yet occurred, selective apoptosis on day 9 was not prevented in moderately hyponatremic rats. Interestingly, treatment with memantine, a noncompetitive NMDAR antagonist, prevented the selective apoptosis in the DG in moderately hyponatremic, ADX rats, and improved electrophysiological dysfunction, including impaired basal synaptic transmission and long-term potentiation at the entorhinal cortex-DG synapses. These results demonstrated that in adrenal insufficient rats, hyponatremia was associated with apoptosis in the DG, and that memantine prevented the apoptosis and improved cell function. Our data imply the importance of assessing the possibility of neurological impairments after treatment with CORT in patients with moderate or severe hyponatremia accompanying adrenal insufficiency and that memantine may represent a beneficial therapeutic strategy to prevent neurological impairments in such patients. (C) 2016 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.expneurol.2016.08.007

Web of Science

PubMed

IgG4関連下垂体炎における抗下垂体抗体の解析

岩田尚子, 岩間信太郎, 安田康紀, 椙村益久, 有馬寛

日本内分泌学会雑誌 Vol. 92 ( 3 ) page： 731 - 731 2017.1

RPH3A蛋白による下垂体後葉炎モデルマウスの開発

安田康紀, 岩間信太郎, 岩田尚子, 椙村益久, 有馬寛

日本内分泌学会雑誌 Vol. 92 ( 3 ) page： 729 - 729 2017.1

イピリムマブ誘発下垂体炎2例の下垂体機能検査およびMRI画像変化に関する検討

岩間信太郎, 小林朋子, 安田康紀, 岩田尚子, 横田憲二, 椙村益久, 安藤雄一, 秋山真志, 有馬寛

日本内分泌学会雑誌 Vol. 92 ( 3 ) page： 731 - 731 2017.1

水バランスの調節バソプレシンニューロンと小胞体ストレス

萩原大輔, 宮田崇, 橡谷昌佳, 東慶成, 森下啓明, 有馬寛

日本内分泌学会雑誌 Vol. 92 ( 3 ) page： 717 - 717 2017.1

家族性中枢性尿崩症モデルマウスに対するケミカルシャペロン4-Phenylbutyric acidの治療効果の検討

橡谷昌佳, 萩原大輔, 宮田崇, 東慶成, 森下啓明, 有馬寛

日本内分泌学会雑誌 Vol. 92 ( 3 ) page： 734 - 734 2017.1

ニボルマブに伴う甲状腺障害に関する前向き臨床研究(中間報告)

岩間信太郎, 小林朋子, 安田康紀, 岩田尚子, 椙村益久, 安藤雄一, 秋山真志, 長谷川好規, 有馬寛

日本内分泌学会雑誌 Vol. 92 ( 3 ) page： 612 - 612 2017.1

マウスES細胞から視床下部神経への誘導法ではグリア細胞も出現する

須賀英隆, 光本一樹, 山田登美子, 加納麻弓子, 水野正明, 有馬寛

日本内分泌学会雑誌 Vol. 92 ( 3 ) page： 732 - 732 2017.1

Clinical practice and mechanism of endocrinological adverse events associated with immune checkpoint inhibitors

Shintaro Iwama, Hiroshi Arima

Japanese Journal of Clinical Immunology Vol. 40 ( 2 ) page： 90 - 94 2017

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japan Society for Clinical Immunology

Immune checkpoint inhibitors, used for cancer immunotherapy, show anti-tumor effects through T cell activations. Monoclonal antibodies against cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed cell death (PD)-1, or PD-ligand 1 which is a ligand of PD-1 have been shown to be effective in the treatments of advanced cancers including malignant melanoma, non-small cell lung cancer, and renal cell carcinoma. However, these drugs also have immune-related adverse events (irAEs). The irAEs, which have unique characteristics different from those seen in conventional cytotoxic anti-tumor medicines, are observed in the several tissues such as skin, gastrointestinal tract, liver, lung, muscle, nerve and endocrine systems. To safely use immune checkpoint inhibitors, it is quite important to understand the characteristics of irAEs and to manage them in clinical practice. In this review, we focus on clinical characteristics and pathogenesis of adverse events in the pituitary gland.

DOI： 10.2177/jsci.40.90

Scopus

PubMed

Normalization of Bilateral Adrenal Gland Enlargement after Treatment for Cryptococcosis

Muraoka Yuka, Iwama Shintaro, Arima Hiroshi

CASE REPORTS IN ENDOCRINOLOGY Vol. 2017 page： 1543149 2017

BMP4 and FGF strongly induce differentiation of mouse ES cells into oral ectoderm. Reviewed

Vol. 15 ( 2 ) page： 290-298 2015

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Papers - ARIMA, Hiroshi