Faculty Profiles - ISHIKAWA, Tetsuya

Papers - ISHIKAWA, Tetsuya

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In utero exposure to di(2-ethylhexyl)phthalate suppresses blood glucose and leptin levels in the offspring of wild-type mice. Reviewed International journal

Yumi Hayashi, Yuki Ito, Hisao Naito, Hazuki Tamada, Nozomi Yamagishi, Takaaki Kondo, Tetsuya Ishikawa, Frank J Gonzalez, Tamie Nakajima

Toxicology Vol. 415 page： 49 - 55 2019.3

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

Exposure of pregnant mice to di(2-ethylhexyl)phthalate (DEHP) induces maternal lipid malnutrition and decreases the number of live fetuses/pups. In this study, we aimed to clarify the relationship between maternal lipid malnutrition and the nutritional status of the neonatal, lactational, and adult offspring, as well as the role of peroxisome proliferator-activated receptor α (PPARα) in these relationships. Sv/129 wild-type (mPPARA), Ppara-null, and PPARα-humanized (hPPARA) mice were fed diets containing 0, 0.01, 0.05, or 0.1% DEHP in utero and/or during the lactational stage. The male offspring were killed on postnatal day 2 or 21, or after 11 weeks. Exposure to either 0.05% or 0.1% DEHP during both the in utero and lactational periods decreased serum glucose concentrations in 2-day-old mPPARA offspring. These dosages also decreased both serum and plasma leptin levels in both 2- and 21-day-old mPPARA offspring. In contrast, exposure to DEHP only during the lactational period did not decrease leptin levels, suggesting the importance of in utero exposure to DEHP. Exposure to 0.05% DEHP during the in utero and lactational periods also increased food consumption after weaning in both mPPARA and hPPARA mice; this was not observed in Ppara-null offspring. In conclusion, in utero exposure to DEHP induces neonatal serum glucose malnutrition via PPARα. DEHP also decreases serum and plasma leptin concentrations in offspring during the neonatal and weaning periods, in association with PPARα, which presumably results in increased of food consumption after weaning.

DOI： 10.1016/j.tox.2019.01.008

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Corrigendum to "Intact metabolite profiling of mouse brain by probe electrospray ionization/triple quadrupole tandem mass spectrometry (PESI/MS/MS) and its potential use for local distribution analysis of the brain" [ACA 983 (2017) 160-165]. International journal

Yumi Hayashi, Kei Zaitsu, Tasuku Murata, Tomomi Ohara, Stéphane Moreau, Maiko Kusano, Hiroshi Tanihata, Hitoshi Tsuchihashi, Akira Ishii, Tetsuya Ishikawa

Analytica chimica acta Vol. 1031 page： 196 - 196 2018.11

Effective Transplantation of 2D and 3D Cultured Hepatocyte Spheroids Confirmed by Quantum Dot Imaging Reviewed

Hiroki Okumura, Eri Nanizawa, Anna Nakanishi, Hiroshi Yukawa, Tadahiro Hashita, Takahiro Iwao, Yoshinobu Baba, Tetsuya Ishikawa, Tamihide Matsunaga

Advanced Biosystems Vol. 2 ( 8 ) 2018.8

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

© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Liver transplantation is the most effective treatment for patients with end-stage liver diseases, but hepatocyte transplantation using spheroids is expected to become an alternative strategy owing to the limited number of liver donors. However, the effects of the transplantation route and spheroid size on cell dynamics and the organ-specific accumulation of hepatocytes are not well characterized. In this study, the influence of three delivery routes (tail vein, portal vein, and spleen) and three spheroid sizes (50, 100, and 150 µm in diameter) on the accumulation of human fetal hepatocytes labeled with quantum dots in the liver and other organs (heart, lung, kidney, and spleen) of recipient mice is investigated. Ex vivo fluorescence imaging reveals that the accumulation of transplanted cells in the liver is highest for transplantation via the portal vein compared with other routes. The accumulation efficiency depends on spheroid size, and spheroids with a diameter of 50 µm display greater accumulation than that of spheroids of other sizes. It is concluded that hepatocyte transplantation via the portal vein using small spheroids of 50 µm in diameter may be effective for clinical applications.

DOI： 10.1002/adbi.201800137

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(-)-Epigallocatechin-3-gallate Down-regulates Doxorubicin-induced Overexpression of P-glycoprotein Through the Coordinate Inhibition of PI3K/Akt and MEK/ERK Signaling Pathways

Satonaka Hana, Ishida Kumiki, Takai Miho, Koide Ryoji, Shigemasa Ryota, Ueyama Jun, Ishikawa Tetsuya, Hayashi Kazuhiko, Goto Hidemi, Wakusawa Shinya

ANTICANCER RESEARCH Vol. 37 ( 11 ) page： 6071-6077 2017.11

Effects of Ursodeoxycholic Acid and Insulin on Palmitate-Induced ROS Production and Down-Regulation of PI3K/Akt Signaling Activity

Yokoyama Kunihiro, Tatsumi Yasuaki, Hayashi Kazuhiko, Goto Hidemi, Ishikawa Tetsuya, Wakusawa Shinya

BIOLOGICAL & PHARMACEUTICAL BULLETIN Vol. 40 ( 11 ) page： 2001-2004 2017.11

Utility of Doppler ultrasonography for diagnosing and assessing treatment effects in liver compartment syndrome. Reviewed

Yusuke Ando, Masatoshi Ishigami, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Kazuhiko Hayashi, Tetsuya Ishikawa, Hidemi Goto, Yoshiki Hirooka

Clinical journal of gastroenterology Vol. 10 ( 3 ) page： 265 - 269 2017.6

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

Liver compartment syndrome is a life-threatening complication of hepatic subcapsular hematoma; diagnosis and assessment of treatment effects are therefore important. We report a rare case of liver compartment syndrome due to spontaneous hepatic subcapsular hematoma without any underlying conditions, in which Doppler ultrasonography (US) proved useful in both diagnosis and assessment of treatment effects. A 32-year-old woman experienced sudden epigastralgia and was diagnosed with hepatic subcapsular hematoma in the right lobe, based on contrast-enhanced computed tomography. Hepatic arteriography showed active hemorrhage and Doppler US showed retrograde flow in the right portal vein. From these findings, we diagnosed hepatic subcapsular hematoma complicated with liver compartment syndrome, and performed embolization of the bleeding point and percutaneous hematoma drainage. After these medical procedures, normalized antegrade flow in the right portal vein was observed on Doppler US. No underlying conditions contributing to hematoma were identified. In this case, Doppler US was useful for both diagnosis and assessment of treatment effects in liver compartment syndrome. When we examine patients with hepatic subcapsular hematoma, Doppler US should be used to diagnose the presence of liver compartment syndrome and assess treatment effects.

DOI： 10.1007/s12328-017-0741-4

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Coexistence of Copper in the Iron-Rich Particles of Aceruloplasminemia Brain. Reviewed International journal

Kunihiro Yoshida, Hisao Hayashi, Shinya Wakusawa, Ryota Shigemasa, Ryoji Koide, Tetsuya Ishikawa, Yasuaki Tatsumi, Koichi Kato, Shinji Ohara, Shu-Ichi Ikeda

Biological trace element research Vol. 175 ( 1 ) page： 79 - 86 2017.1

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

The interaction between iron and copper has been discussed in association with human health and diseases for many years. Ceruloplasmin, a multi-copper oxidase, is mainly involved in iron metabolism and its genetic defect, aceruloplasminemia (ACP), shows neurological disorders and diabetes associated with excessive iron accumulation, but little is known about the state of copper in the brain. Here, we investigated localization of these metals in the brains of three patients with ACP using electron microscopes equipped with an energy-dispersive x-ray analyzer. Histochemically, iron deposition was observed mainly in the basal ganglia and dentate nucleus, and to lesser degree in the cerebral cortex of the patients, whereas copper grains were not detected. X-ray microanalysis identified two types of iron-rich particles in their brains: dense bodies, namely hemosiderins, and their aggregated inclusions. A small number of hemosiderins and most inclusions contained a significant amount of copper which was enough for distinct Cu x-ray images. These copper-containing particles were observed more frequently in the putamen and dentate nucleus than the cerebral cortex. Coexistence of iron and copper was supported by good correlations in the molecular ratios between these two metals in iron-rich particles with Cu x-ray image. Iron-dependent copper accumulation in iron-rich particles may suggest that copper recycling is enhanced to meet the increased requirement of cuproproteins in iron overload brain. In conclusion, the iron-rich particles with Cu x-ray image were found in the ACP brain.

DOI： 10.1007/s12011-016-0744-x

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近赤外バイオイメージング-NIR-II:第2の生体の窓 NIR-II近赤外領域における移植幹細胞in vivo蛍光イメージング

湯川博, 小林香央里, 湯川博, 小林香央里, 新岡宏彦, 亀山達矢, 佐藤和秀, 鳥本司, 石川哲也, 馬場嘉信, 馬場嘉信

Bio Industry Vol. 34 ( 1 ) page： 113 - 113 2017

Metabolome analysis revealed that abnormal muscular contraction is related to both metabolic alterations and hyper-thermogenesis in the serotonin syndrome

ZAITSU Kei, NODA Saki, HAYASHI Yumi, OHARA Tomomi, IGUCHI Akira, KUSANO Maiko, SATO Takako, TSUCHIHASHI Hitoshi, ISHIKAWA Tetsuya, SUZUKI Koichi, ISHII Akira

Annual Meeting of the Japanese Society of Toxicology Vol. 44.1 ( 0 ) page： O-38 2017

Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 identified from Dental Pulp Stem Cells Synergistically Resolve Acute Liver Failure in Rats by Altering Macrophage Polarity Reviewed

Takanori Ito, Akihito Yamamoto, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Tetsuya Ishikawa, Masatoshi Ishigami, Yoshiki Hirooka, Hidemi Goto

HEPATOLOGY Vol. 64 page： 515A - 515A 2016.10

Investigation of cocaine-induced hepatic injury in PPARα-null mice on the basis of lipid mediators and metabolome analyses

SHINODA Satoshi, HAYASHI Yumi, ZAITSU Kei, SAKAI Yuichiro, YAMANAKA Mayumi, NASU Tamie, ISHIKAWA Tetsuya, YOSHIMOTO Takashi, KUSANO Maiko, TSUCHIHASHI Hitoshi, ISHII Akira

Annual Meeting of the Japanese Society of Toxicology Vol. 43.1 ( 0 ) page： P-90 2016

[Pathogenesis and disease state in hepatitis B virus infection].

Ishikawa T

Nihon rinsho. Japanese journal of clinical medicine Vol. 73 Suppl 9 page： 429 - 33 2015.12

C型肝炎治療の現状 Invited

石川哲也

明日の臨床 Vol. 27 ( 1 ) page： 29-34 2015.6

Kynurenine production mediated by indoleamine 2,3-dioxygenase aggravates liver injury in HBV-specific CTL-induced fulminant hepatitis. Reviewed

OHTAKI Hirofumi, ITO Hiroyasu, ANDO Kazuki, ISHIKAWA Tetsuya, HOSHI Masato, ANDO Tatsuya, TAKAMATSU Manabu, HARA Akira, MORIWAKI Hisataka, SAITO Kuniaki, SEISHIMA Mitsuru

Biochim Biophys Acta Vol. 1842 ( 9 ) page： 1464–1471 2014.9

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

Indoleamine 2,3-dioxygenase (IDO), an enzyme that is ubiquitously distributed in mammalian tissues and cells, converts tryptophan to kynurenine, and is also known as a key molecule that promotes apoptosis in lymphocytes and neurons. In this study, we established hepatitis B virus (HBV)-transgenic (Tg)/IDO-knockout (KO) mice and examined the influence of IDO in a murine fulminant hepatitis model induced by HBV-specific cytotoxic T lymphocytes (CTL). An increase of IDO expression in the livers of HBV-Tg/IDO-wild-type (WT) mice administered HBV-specific CTL was confirmed by real-time polymerase chain reaction, western blotting, and evaluating IDO activity. Plasma alanine aminotransferase (ALT) levels in HBV-Tg/IDO-KO mice after HBV-specific CTL injection significantly decreased compared with those in HBV-Tg/IDO-WT mice. An inhibitor of IDO, 1-methyl-D-tryptophan (1-MT), could also attenuated the observed liver injury induced by this HBV-specific CTL. The expression levels of cytokine and chemokine mRNAs in the livers of HBV-Tg/IDO-WT mice were higher than those in the livers of HBV-Tg/IDO-KO mice. The administration of kynurenine aggravated the liver injury in HBV-Tg/IDO-KO mice injected with HBV-specific CTL. Simultaneous injection of recombinant murine interferon (IFN-γ) and kynurenine also increased the ALT levels in HBV-Tg/IDO-KO mice. The liver injury
induced by IFN-γ and kynurenine was improved in HBV-Tg/tumor necrosis factor-α-KO mice. Conclusion:
Kynurenine and IFN-γ induced by the administration with HBV-specific CTL are cooperatively involved in the
progression of liver injury in acute hepatitis model. Our results may lead to a new therapy for the acute liver injury caused by HBV infection.

Induction of hepatitis B virus surface antigen-specific cytotoxic T lymphocytes can be up-regulated by the inhibition of indoleamine 2, 3-dioxygenase activity. Reviewed

ITO Hiroyasu, ANDO Tatsuya, ANDO Kazuki, ISHIKAWA Tetsuya, SAITO Kuniaki, MORIWAKI Hisataka, SEISHIMA Mitsuru

Immunology Vol. 142 ( 4 ) page： 614–623 2014.8

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

Cytotoxic T lymphocytes (CTLs) are thought to be major effectors involved in viral clearance during acute infections, including hepatitis B virus (HBV) infection. A persistent HBV infection is characterized by a lack of or a weak CTL response to HBV, which may be reflective of tolerance to HBV. Efficient induction of HBV-specific CTLs leads to the clearance of HBV in patients with a chronic HBV infection. Previously, we
reported that a-galactosylceramide (a-GalCer), a specific natural killer T (NKT) cell agonist, enhanced the induction of HBV surface antigen (HBsAg)-specific CTLs. In the present study, we found that inhibition of
indoleamine 2,3-dioxygenase (IDO) activity enhanced the induction of HBsAg-specific CTLs after immunization with HBsAg and a-GalCer. The administration of HBsAg and a-GalCer increased the production of interleukin-2 and interleukin-12b, which are crucial for the induction of HBsAg-specific CTLs. The production of these cytokines was more strongly enhanced in IDO knockout mice compared with wild-type mice. In addition, a-GalCer induced the production of IDO in CD11b+ cells, and these cells inhibited proliferation of HBsAg-specific CTLs. Our results lead to strategies for improving the induction of HBsAg-specific CTLs.

Ursodeoxycholic acid inhibits overexpression of P-glycoprotein induced bydoxorubicin in HepG2 cells. Reviewed

KOMORI Yuki, ARISAWA Sakiko, TAKAI Miho, YOKOYAMA Kunihiro, HONDA Minako, HAYASHI Kazuhiko, ISHIGAMI Masatoshi, KATANO Yoshiaki, GOTO Hidemi, UEYAMA Jun, ISHIKAWA Tetsuya, WAKUSAWA Shinya.

European JournalofPharmacology Vol. 724 page： 161-167 2014.2

進行肝細胞癌に対するソラフェニブ投与後2週間以内の発熱と造影CT上の阻血性変化との関係 Reviewed

葛谷貞二、石上雅敏、新家卓郎、今井則博、阿知波宏一、荒川恭宏、山田恵一、中野聡、石津洋二、本多隆、林和彦、石川哲也、中野功、片野義明、伊藤彰浩、廣岡芳樹、後藤秀実.

肝臓 Vol. 54 ( 7 ) page： 505-506 2013.7

満腹感を伴う便秘症状の原因にvildagliptinの関与が示唆された糖尿病合併末期腎不全の1例 Reviewed

綾田穣、森弘卓延、加藤ふみ、堀田直樹、黒川剛、中野達徳、石川哲也

腎と透析 Vol. 74 ( 3 ) page： 470-474 2013.3

Clinical trial of percutaneous radio frequency ablation therapy by two-step insertion method using VirtuTRAXTM instrument navigator Reviewed

Kuzuya Teiji, Hayashi Kazuhiko, Ishigami Masatoshi, Ishikawa Tetsuya, Nakano Isao, Katano Yoshiaki, Itoh Akihiro, Hirooka Yoshiki, Izumi Namiki, Goto Hidemi, Ishizu Yoji, Niinomi Takurou, Imai Norihiro, Achiwa Kouichi, Arakawa Takahiro, Yamada Keiichi, Nakano Satoshi, Honda Takashi

Kanzo Vol. 54 ( 12 ) page： 850 - 853 2013

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japan Society of Hepatology

We performed percutaneous radio frequency ablation (RFA) therapy by two-step insertion method using VirtuTRAXTM (GE Healthcare, USA) instrument navigator. Subjects were 16 patients (23 nodules) with hepatocellular carcinoma. VirtuTRAXTM position sensor was attached to the hilt of 14-gauge outer needle. In all cases, we could perform 17- gauge Cool-tip RFA without the positional gap between the virtual tract and the actual needle which was caused by the deflection of the needle. The reasons without causing the positional gap were that the outer needle was more rigid than Cool-tip needle, and that it was inserted using initial insertion of a 21-gauge guided needle. RFA by two-step insertion method using VirtuTRAXTM is suggested to be more safe and effective than conventional RFA.

DOI： 10.2957/kanzo.54.850

Other Link： http://search.jamas.or.jp/link/ui/2014089120

Quantum dots conjugated with transferrin for brain tumor cell imaging.

Yukawa H, Tsukamoto R, Kano A, Okamoto Y, Tokeshi M, Ishikawa T, Mizuno M, Baba Y

Journal of Cell Science and Therapy Vol. 4 ( 3 ) page： 1 2013

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Papers - ISHIKAWA, Tetsuya