TOHOKU UNIVERSITY Researchers - Yoshihisa Tomioka

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Yoshihisa Tomioka

Section

Graduate School of Pharmaceutical Sciences

Job title

Professor

Degree

博士（薬学）（東北大学）
薬学修士（東北大学）

researchmap

https://researchmap.jp/read0145743

J-GLOBAL ID

200901091454670349

Committee Memberships 6

薬学教育協議会東北地区調整機構　大学委員

2009/04 - Present
日本薬剤師研修センター宮城県協議会　委員

2002/04 - 2003/09
宮城県病院薬剤師会学術情報委員会　委員

1998/04 - 2003/09
２００２ＦＩＦＡワールドカップ宮城開催における集団災害救急医療対策プロジェクトワーキンググループ員　薬事担当

2002/02 - 2002/06
日本ＴＤＭ学会第１７回日本ＴＤＭ学会学術大会準備運営委員会　委員

1999/04 - 2000/06
Bio-Net運営ワークグループ　員

1990/04 - 2000/03

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Professional Memberships 6

日本臨床腫瘍学会
日本医療薬学会
日本免疫学会
日本生化学会
日本癌学会
日本薬学会

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Research Areas 3

Life sciences / Tumor diagnostics and therapeutics /
Life sciences / Clinical pharmacy /
Life sciences / Functional biochemistry /

Papers 184

Isomaltodextrin inhibits kidney enlargement induced by a high-protein diet through its metabolism by gut microbiota. International-journal

Ryodai Takagaki, Jun Takahashi, Shin Endo, Ryota Kujirai, Mizuki Abe, Koichi Kikuchi, Chitose Suzuki, Yotaro Matsumoto, Yoshihisa Tomioka, Takaaki Abe, Hidetoshi Morita

Bioscience, biotechnology, and biochemistry　2024/12/06

DOI： 10.1093/bbb/zbae188 　

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To evaluate the effects of the soluble fiber isomaltodextrin in a protein-biased diet, a 21-day protein diet trial was conducted in rats, with 60% of the calories derived from protein. The results revealed that the high-protein diet alone led to a significant increase in kidney weight. In contrast, the consumption of water with 5% isomaltodextrin dissolved in it, along with a high-protein diet, suppressed this weight gain. To elucidate this mechanism, an analysis of serum urea toxins confirmed that the concentrations of phenyl sulfate were significantly higher with high protein, and significantly lower with isomaltodextrin. The impact of a high-protein on increased phenol in cecal contents, an increased that was mitigated by the isomaltodextrin. This suggests that the inhibitory effect of isomaltodextrin on renal hypertrophy was due to the suppression of urea toxin precursor production by the gut microbiota.
Development of a LC–MS/MS analytical method of 15 compounds related to renal function for a prognostic method of progression risk in patients with diabetic kidney disease

Ryota Kujirai, Yotaro Matsumoto, Mizuki Abe, Kodai Hiramoto, Takumi Watanabe, Chitose Suzuki, Takafumi Toyohara, Takaaki Abe, Yoshihisa Tomioka

Journal of Pharmaceutical and Biomedical Analysis Open　2　100021-100021　2023/12
Publisher: Elsevier BV
DOI： 10.1016/j.jpbao.2023.100021 　

ISSN： 2949-771X
Chronopharmacology of diuresis via metabolic profiling and key biomarker discovery of the Traditional Chinese Prescription Ji-Ming-San using tandem mass spectrometry in rat models

Cheng-Yang Hsieh, Po-Wei Tsai, Yoshihisa Tomioka, Yotaro Matsumoto, Yasutoshi Akiyama, Ching-Chiung Wang, Lemmuel L. Tayo, Chia-Jung Lee

Phytomedicine　155260-155260　2023/12
Publisher: Elsevier BV
DOI： 10.1016/j.phymed.2023.155260 　

ISSN： 0944-7113
Toll様受容体4刺激抗体は食物アレルギーを予防、抑制する

塚本宏樹, 小林洋平, 渡邉悠理香, 渡邊康一, 富岡佳久

日本生化学会大会プログラム・講演要旨集　96回　[2P-612]　2023/10
Publisher: (公社)日本生化学会
Urinary growth differentiation factor 15 predicts renal function decline in diabetic kidney disease. International-journal

Toma Oshita, Shun Watanabe, Takafumi Toyohara, Ryota Kujirai, Koichi Kikuchi, Takehiro Suzuki, Chitose Suzuki, Yotaro Matsumoto, Jun Wada, Yoshihisa Tomioka, Tetsuhiro Tanaka, Takaaki Abe

Scientific reports　13　(1)　12508-12508　2023/08/02

DOI： 10.1038/s41598-023-39657-7 　

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Sensitive biomarkers can enhance the diagnosis, prognosis, and surveillance of chronic kidney disease (CKD), such as diabetic kidney disease (DKD). Plasma growth differentiation factor 15 (GDF15) levels are a novel biomarker for mitochondria-associated diseases; however, it may not be a useful indicator for CKD as its levels increase with declining renal function. This study explores urinary GDF15's potential as a marker for CKD. The plasma and urinary GDF15 as well as 15 uremic toxins were measured in 103 patients with CKD. The relationship between the urinary GDF15-creatinine ratio and the uremic toxins and other clinical characteristics was investigated. Urinary GDF15-creatinine ratios were less related to renal function and uremic toxin levels compared to plasma GDF15. Additionally, the ratios were significantly higher in patients with CKD patients with diabetes (p = 0.0012) and reduced with statin treatment. In a different retrospective DKD cohort study (U-CARE, n = 342), multiple and logistic regression analyses revealed that the baseline urinary GDF15-creatinine ratios predicted a decline in estimated glomerular filtration rate (eGFR) over 2 years. Compared to the plasma GDF15 level, the urinary GDF15-creatinine ratio is less dependent on renal function and sensitively fluctuates with diabetes and statin treatment. It may serve as a good prognostic marker for renal function decline in patients with DKD similar to the urine albumin-creatinine ratio.
Drugs activating hypoxia-inducible factors correct erythropoiesis and hepcidin levels via renal EPO induction in mice. International-journal

Taku Nakai, Yuma Iwamura, Koichiro Kato, Ikuo Hirano, Yotaro Matsumoto, Yoshihisa Tomioka, Masayuki Yamamoto, Norio Suzuki

Blood advances　2023/05/05

DOI： 10.1182/bloodadvances.2023009798 　

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The erythroid growth factor erythropoietin (EPO) is mainly produced by the kidneys in adult mammals and induces expansion of erythroid cells and iron use for hemoglobin synthesis. The liver also produces EPO at a lower level than the kidneys. Renal and hepatic EPO production is fundamentally regulated by hypoxia-inducible transcription factors (HIFs) in a hypoxia/anemia-inducible manner. Recently, small compounds that activate HIFs and EPO production in the kidneys by inhibiting HIF-prolyl hydroxylases (HIF-PHIs) have been launched to treat EPO-deficiency anemia in patients suffering from kidney disease. However, the roles of the liver in the HIF-PHI-mediated induction of erythropoiesis and iron mobilization remain controversial. Here, to elucidate the liver contributions to the therapeutic effects of HIF-PHIs, genetically modified mouse lines lacking renal EPO-production ability were analyzed. In the mutant mice, HIF-PHI administration marginally increased plasma EPO concentrations and peripheral erythrocytes by inducing hepatic EPO production. The effects of HIF-PHIs on the mobilization of stored iron and on the suppression of hepatic hepcidin, an inhibitory molecule for iron release from iron-storage cells, were not observed in the mutant mice. These findings demonstrate that adequate induction of EPO mainly in the kidney is essential for achieving the full therapeutic effects of HIF-PHIs, which include hepcidin suppression. The data also show that HIF-PHIs directly induce the expression of duodenal genes related to dietary iron intake. Additionally, hepatic EPO induction is considered to partially contribute to the erythropoietic effects of HIF-PHIs but to be insufficient to compensate for the abundant EPO induction by the kidneys.
Elobixibat投与マウスにおける胆汁酸および腸内細菌叢の検討

蓑輪圭太, 秋山由雅子, 笠原朋子, 何欣蓉, 前川正充, 菊池晃一, 豊原敬文, 鈴木健弘, 鈴木千登世, 鯨井涼太, 松本洋太郎, 富岡佳久, 阿部高明

日本腎臓学会誌　65　(3)　294-294　2023/05
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
<scp>CD98</scp> regulates the phosphorylation of <scp>HER2</scp> and a bispecific <scp>anti‐HER2</scp> / <scp>CD98</scp> antibody inhibits the growth signal of human breast cancer cells

Akitaka Yamasaki, Kumiko Maruyama‐Takahashi, Kento Nishida, Shogo Okazaki, Kouki Okita, Yasutoshi Akiyama, Hideaki Suzuki, Yuichi Endo, Kazue Masuko, Takashi Masuko, Yoshihisa Tomioka

Genes to Cells　2023/02/21
Publisher: Wiley
DOI： 10.1111/gtc.13016 　

ISSN： 1356-9597

eISSN： 1365-2443
Diverse and divergent functions of IL-32β and IL-32γ isoforms in the regulation of malignant pleural mesothelioma cell growth and the production of VEGF-A and CXCL8

Muneo Numasaki, Koyu Ito, Kiyoshi Takagi, Kengo Nagashima, Hirotsugu Notsuda, Hirokazu Ogino, Rika Ando, Yoshihisa Tomioka, Takashi Suzuki, Yoshinori Okada, Yasuhiko Nishioka, Michiaki Unno

Cellular Immunology　104652-104652　2022/11
Publisher: Elsevier BV
DOI： 10.1016/j.cellimm.2022.104652 　

ISSN： 0008-8749
RTCB Complex Regulates Stress-Induced tRNA Cleavage Peer-reviewed

Yasutoshi Akiyama, Yoshika Takenaka, Tomoko Kasahara, Takaaki Abe, Yoshihisa Tomioka, Pavel Ivanov

International Journal of Molecular Sciences　23　(21)　13100-13100　2022/10/28
Publisher: {MDPI} {AG}
DOI： 10.3390/ijms232113100 　

ISSN： 1422-0067

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<jats:p>Under stress conditions, transfer RNAs (tRNAs) are cleaved by stress-responsive RNases such as angiogenin, generating tRNA-derived RNAs called tiRNAs. As tiRNAs contribute to cytoprotection through inhibition of translation and prevention of apoptosis, the regulation of tiRNA production is critical for cellular stress response. Here, we show that RTCB ligase complex (RTCB-LC), an RNA ligase complex involved in endoplasmic reticulum (ER) stress response and precursor tRNA splicing, negatively regulates stress-induced tiRNA production. Knockdown of RTCB significantly increased stress-induced tiRNA production, suggesting that RTCB-LC negatively regulates tiRNA production. Gel-purified tiRNAs were repaired to full-length tRNAs by RtcB in vitro, suggesting that RTCB-LC can generate full length tRNAs from tiRNAs. As RTCB-LC is inhibited under oxidative stress, we further investigated whether tiRNA production is promoted through the inhibition of RTCB-LC under oxidative stress. Although hydrogen peroxide (H2O2) itself did not induce tiRNA production, it rapidly boosted tiRNA production under the condition where stress-responsive RNases are activated. We propose a model of stress-induced tiRNA production consisting of two factors, a trigger and booster. This RTCB-LC-mediated boosting mechanism may contribute to the effective stress response in the cell.</jats:p>
尿毒素フェニル硫酸は糖尿病性腎症におけるインスリン分泌促進とインスリン抵抗性に関与する

頓宮慶泰, 菊地晃一, 鈴木健新, 三瀬広記, 和田淳, 秋山泰利, 那谷耕司, 鯨井涼太, 松本洋太郎, 富岡佳久, 渡邉駿, 豊原敬文, 鈴木健弘, 田中哲弘, 阿部高明

日本高血圧学会総会プログラム・抄録集　44回　77-77　2022/10
Publisher: (NPO)日本高血圧学会
糖尿病性腎症の新規予後予測マーカーとしての尿中フェニル硫酸

菊地晃一, 鯨井涼太, 松本洋太郎, 中村智洋, 三瀬広記, 渡邉駿, 豊原敬文, 鈴木健弘, 和田淳, 富岡佳久, 阿部高明

日本腎臓学会誌　64　(3)　290-290　2022/05
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
修飾核酸一斉定量系を用いたCOPD・肺がん鑑別手法の検討

渡辺匠, 平本航大, 沼倉忠久, 宮内栄作, 突田容子, 杉浦久敏, 松本洋太郎, 富岡佳久

日本薬学会年会要旨集　142年会　26M-pm08S　2022/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
Esterification promotes the intracellular accumulation of roxadustat, an activator of hypoxia-inducible factors, to extend its effective duration. International-journal

Taku Nakai, Daisuke Saigusa, Yuma Iwamura, Yotaro Matsumoto, Keiko Umeda, Koichiro Kato, Hayato Yamaki, Yoshihisa Tomioka, Ikuo Hirano, Seizo Koshiba, Masayuki Yamamoto, Norio Suzuki

Biochemical pharmacology　197　114939-114939　2022/03

DOI： 10.1016/j.bcp.2022.114939 　

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Kidney injury often causes anemia due to a lack of production of the erythroid growth factor erythropoietin (EPO) in the kidneys. Roxadustat is one of the first oral medicines inducing EPO production in patients with renal anemia by activating hypoxia-inducible factors (HIFs), which are activators of EPO gene expression. In this study, to develop prodrugs of roxadustat with improved permeability through cell membrane, we investigated the effects of 8 types of esterification on the pharmacokinetics and bioactivity of roxadustat using Hep3B hepatoma cells that HIF-dependently produce EPO. Mass spectrometry of cells incubated with the esterified roxadustat derivatives revealed that the designed compounds were deesterified after being taken up by cells and showed low cytotoxicity compared to the original compound. Esterification prolonged the effective duration of roxadustat with respect to EPO gene induction and HIF activation in cells transiently exposed to the compounds. In the kidneys and livers of mice, both of which are unique sites of EPO production, a majority of the methyl-esterified roxadustat was deesterified within 6 h after drug administration. The deesterified roxadustat derivative was continuously detectable in plasma and urine for at least 48 h after administration, while the administered compound became undetectable 24 h after administration. Additionally, we confirmed that methyl-esterified roxadustat activated erythropoiesis in mice by inducing Epo mRNA expression exclusively in renal interstitial cells, which have intrinsic EPO-producing potential. These data suggest that esterification could lead to the development of roxadustat prodrugs with improvements in cell membrane permeability, effective duration and cytotoxicity.
Selective Cleavage at CCA Ends and Anticodon Loops of tRNAs by Stress-Induced RNases

Yasutoshi Akiyama, Shawn M. Lyons, Marta M. Fay, Yoshihisa Tomioka, Takaaki Abe, Paul J. Anderson, Pavel Ivanov

Frontiers in Molecular Biosciences　9　2022/03/01
Publisher: Frontiers Media SA
DOI： 10.3389/fmolb.2022.791094 　

eISSN： 2296-889X

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Stress-induced tRNA cleavage has been implicated in various cellular processes, where tRNA fragments play diverse regulatory roles. Angiogenin (ANG), a member of the RNase A superfamily, induces cleavage of tRNAs resulting in the formation of tRNA-derived stress-induced RNAs (tiRNAs) that contribute to translational reprogramming aiming at cell survival. In addition to cleaving tRNA anticodon loops, ANG has been shown to cleave 3′-CCA termini of tRNAs <italic>in vitro</italic>, although it is not known whether this process occurs in cells. It has also been suggested that tiRNAs can be generated independently of ANG, although the role of other stress-induced RNases in tRNA cleavage is poorly understood. Using gene editing and biochemical approaches, we examined the involvement of ANG in stress-induced tRNA cleavage by focusing on its cleavage of CCA-termini as well as anticodon loops. We show that ANG is not responsible for CCA-deactivation under sodium arsenite (SA) treatment <italic>in cellulo</italic>, and although ANG treatment significantly increases 3′-tiRNA levels in cells, the majority of 3′-tiRNAs retain their 3′-CCA termini. Instead, other RNases can cleave CCA-termini in cells, although with low efficiency. Moreover, in the absence of ANG, other RNases are able to promote the production of tiRNAs in cells. Depletion of RNH1 (an endogenous inhibitor of RNase A superfamily) promotes constitutively-produced tiRNAs and CCA-deactivated tRNAs in cells. Interestingly, SA treatment in RNH1-depleted cells did not increase the amount of tiRNAs or CCA-deactivated tRNAs, suggesting that RNase A superfamily enzymes are largely responsible for SA-induced tRNA cleavage. We show that interplay between stress-induced RNases cause targeting tRNAs in a stress-specific manner <italic>in cellulo</italic>.
Nrf2 plays a critical role in the metabolic response during and after spaceflight. International-journal

Akira Uruno, Daisuke Saigusa, Takafumi Suzuki, Akane Yumoto, Tomohiro Nakamura, Naomi Matsukawa, Takahiro Yamazaki, Ristumi Saito, Keiko Taguchi, Mikiko Suzuki, Norio Suzuki, Akihito Otsuki, Fumiki Katsuoka, Eiji Hishinuma, Risa Okada, Seizo Koshiba, Yoshihisa Tomioka, Ritsuko Shimizu, Masaki Shirakawa, Thomas W Kensler, Dai Shiba, Masayuki Yamamoto

Communications biology　4　(1)　1381-1381　2021/12/09

DOI： 10.1038/s42003-021-02904-6 　

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Space travel induces stresses that contribute to health problems, as well as inducing the expression of Nrf2 (NF-E2-related factor-2) target genes that mediate adaptive responses to oxidative and other stress responses. The volume of epididymal white adipose tissue (eWAT) in mice increases during spaceflight, a change that is attenuated by Nrf2 knockout. We conducted metabolome analyses of plasma from wild-type and Nrf2 knockout mice collected at pre-flight, in-flight and post-flight time points, as well as tissues collected post-flight to clarify the metabolic responses during and after spaceflight and the contribution of Nrf2 to these responses. Plasma glycerophospholipid and sphingolipid levels were elevated during spaceflight, whereas triacylglycerol levels were lower after spaceflight. In wild-type mouse eWAT, triacylglycerol levels were increased, but phosphatidylcholine levels were decreased, and these changes were attenuated in Nrf2 knockout mice. Transcriptome analyses revealed marked changes in the expression of lipid-related genes in the liver and eWAT after spaceflight and the effects of Nrf2 knockout on these changes. Based on these results, we concluded that space stress provokes significant responses in lipid metabolism during and after spaceflight; Nrf2 plays critical roles in these responses.
SGLT‐1‐specific inhibition ameliorates renal failure and alters the gut microbial community in mice with adenine‐induced renal failure

Hsin‐Jung Ho, Koichi Kikuchi, Daiki Oikawa, Shun Watanabe, Yoshitomi Kanemitsu, Daisuke Saigusa, Ryota Kujirai, Wakako Ikeda‐Ohtsubo, Mariko Ichijo, Yukako Akiyama, Yuichi Aoki, Eikan Mishima, Yoshiaki Ogata, Yoshitsugu Oikawa, Tetsuro Matsuhashi, Takafumi Toyohara, Chitose Suzuki, Takehiro Suzuki, Nariyasu Mano, Yoshiteru Kagawa, Yuji Owada, Takane Katayama, Toru Nakayama, Yoshihisa Tomioka, Takaaki Abe

Physiological Reports　9　(24)　2021/12
Publisher: Wiley
DOI： 10.14814/phy2.15092 　

ISSN： 2051-817X

eISSN： 2051-817X
ヒトToll様受容体4を抑制する低分子組換え抗体の発現と機能評価

塚本宏樹, 鵜飼一歩, 山形由貴, 武内偲乃, 富岡佳久

日本生化学会大会プログラム・講演要旨集　94回　[P-1016]　2021/11
Publisher: (公社)日本生化学会
血中・尿中GDF15の糖尿病性腎症および腎内環境の予測因子としての有用性の臨床検討

大下冬馬, 豊原敬文, 渡邉駿, 菊池晃一, 鈴木健弘, 鯨井涼太, 宮崎真理子, 富岡佳久, 阿部高明

日本高血圧学会総会プログラム・抄録集　43回　269-269　2021/10
Publisher: (NPO)日本高血圧学会
In lysate RNA digestion provides insights into the angiogenin’s specificity towards transfer RNAs

Yasutoshi Akiyama, Yoshihisa Tomioka, Takaaki Abe, Paul Anderson, Pavel Ivanov

RNA Biology　1-10　2021/06/04
Publisher: Informa UK Limited
DOI： 10.1080/15476286.2021.1930758 　

ISSN： 1547-6286

eISSN： 1555-8584
腸内細菌叢と胆汁酸の調節による腎不全治療

秋山由雅子, 前川正充, 菊地晃一, 何欣蓉, 一條真梨子, 鈴木千登世, 渡邉駿, 豊原敬文, 鈴木健弘, 富岡佳久, 阿部高明

日本腎臓学会誌　63　(4)　459-459　2021/06
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
腸内細菌叢と胆汁酸の調節による腎不全治療

秋山由雅子, 前川正充, 菊地晃一, 何欣蓉, 一條真梨子, 鈴木千登世, 渡邉駿, 豊原敬文, 鈴木健弘, 富岡佳久, 阿部高明

日本腎臓学会誌　63　(4)　459-459　2021/06
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
血液透析とオンライン血液濾過透析による血中フェノール誘導体,核酸除去率の比較

島久登, 道脇宏行, 三島英換, 金光祥臣, 富岡佳久, 岡田一義, 阿部高明, 水口潤

日本透析医学会雑誌　54　(Suppl.1)　457-457　2021/05
Publisher: (一社)日本透析医学会
ISSN： 1340-3451

eISSN： 1883-082X
CE-MS-Based Identification of Uremic Solutes Specific to Hemodialysis Patients

Yasutoshi Akiyama, Koichi Kikuchi, Takafumi Toyohara, Eikan Mishima, Chitose Suzuki, Takehiro Suzuki, Masaaki Nakayama, Yoshihisa Tomioka, Tomoyoshi Soga, Takaaki Abe

Toxins　13　(5)　324-324　2021/04/30
Publisher: MDPI AG
DOI： 10.3390/toxins13050324 　

eISSN： 2072-6651

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Uremic toxins are suggested to be involved in the pathophysiology of hemodialysis (HD) patients. However, the profile of uremic solutes in HD patients has not been fully elucidated. In this study using capillary electrophoresis mass spectrometry (CE-MS), we comprehensively quantified the serum concentrations of 122 ionic solutes before and after HD in 11 patients. In addition, we compared the results with those in non-HD patients with chronic kidney disease (CKD) to identify HD patient-specific solutes. We identified 38 solutes whose concentrations were higher in pre-HD than in CKD stage G5. Ten solutes among them did not significantly accumulate in non-HD CKD patients, suggesting that these solutes accumulate specifically in HD patients. We also identified 23 solutes whose concentrations were lower in both pre- and post-HD than in CKD stage G5. The serum levels of 14 solutes among them were not affected by renal function in non-HD patients, suggesting that these solutes tend to be lost specifically in HD patients. Our data demonstrate that HD patients have a markedly different profile of serum uremic solute levels compared to that in non-HD CKD patients. The solutes identified in our study may contribute to the pathophysiology of HD patients.
ヒトperoxiredoxin 4モノクローナル抗体の作製とエピトープ解析

塚本宏樹, 紫竹歩, 後藤裕徳, 小坂井沙緒, 富岡佳久, 池田義孝

日本生化学会大会プログラム・講演要旨集　93回　[P-215]　2020/09
Publisher: (公社)日本生化学会
ヒトperoxiredoxin 4モノクローナル抗体の作製とエピトープ解析

塚本宏樹, 紫竹歩, 後藤裕徳, 小坂井沙緒, 富岡佳久, 池田義孝

日本生化学会大会プログラム・講演要旨集　93回　[P-215]　2020/09
Publisher: (公社)日本生化学会
血液透析とオンライン血液濾過透析による血中フェノール誘導体、核酸除去率の検討

島久登, 道脇宏行, 金光祥臣, 三島英換, 鈴木千登世, 田尾知浩, 岡田一義, 富岡佳久, 阿部高明, 水口潤

日本腎臓学会誌　62　(4)　351-351　2020/07
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
アデニン誘発腎不全マウスにおけるエロビキシバットの効果

秋山由雅子, 前川正充, 金光祥臣, 菊地晃一, 何欣蓉, 三島英換, 鈴木健弘, 一條真梨子, 鈴木千登世, 眞野成康, 富岡佳久, 阿部高明

日本腎臓学会誌　62　(4)　337-337　2020/07
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
糖尿病性腎症の発症・進展予測マーカーとしてのフェニル硫酸の有用性

菊地晃一, 三枝大輔, 金光祥臣, 松本洋太郎, 三瀬広記, 中村智洋, 三島英換, 豊原敬文, 鈴木健弘, 寳澤篤, 和田淳, 富岡佳久, 阿部高明

日本腎臓学会誌　62　(4)　276-276　2020/07
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
糖尿病性腎症の発症・進展予測マーカーとしてのフェニル硫酸の有用性

菊地晃一, 三枝大輔, 金光祥臣, 松本洋太郎, 三瀬広記, 中村智洋, 三島英換, 豊原敬文, 鈴木健弘, 寳澤篤, 和田淳, 富岡佳久, 阿部高明

日本腎臓学会誌　62　(4)　276-276　2020/07
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
血液透析とオンライン血液濾過透析による血中フェノール誘導体、核酸除去率の検討

島久登, 道脇宏行, 金光祥臣, 三島英換, 鈴木千登世, 田尾知浩, 岡田一義, 富岡佳久, 阿部高明, 水口潤

日本腎臓学会誌　62　(4)　351-351　2020/07
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
アデニン誘発腎不全マウスにおけるエロビキシバットの効果

秋山由雅子, 前川正充, 金光祥臣, 菊地晃一, 何欣蓉, 三島英換, 鈴木健弘, 一條真梨子, 鈴木千登世, 眞野成康, 富岡佳久, 阿部高明

日本腎臓学会誌　62　(4)　337-337　2020/07
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
Global metabolomics analysis of serum from patients with Niemann-Pick disease type C Peer-reviewed

Anna Iwahori, Masamitsu Maekawa, Yoshitomi Kanemitsu, Yotaro Matsumoto, Yoshihisa Tomioka, Aya Narita, Torayuki Okuyama, Yoshikatsu Eto, Daisuke Saigusa, Nariyasu Mano

Medical Mass Spectrometry　4　(1)　1-11　2020/05
Metabolic basis of neuronal vulnerability to ischemia; an in vivo untargeted metabolomics approach. International-journal Peer-reviewed

Sherif Rashad, Daisuke Saigusa, Takahiro Yamazaki, Yotaro Matsumoto, Yoshihisa Tomioka, Ritsumi Saito, Akira Uruno, Kuniyasu Niizuma, Masayuki Yamamoto, Teiji Tominaga

Scientific reports　10　(1)　6507-6507　2020/04/16

DOI： 10.1038/s41598-020-63483-w 　

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Understanding the root causes of neuronal vulnerability to ischemia is paramount to the development of new therapies for stroke. Transient global cerebral ischemia (tGCI) leads to selective neuronal cell death in the CA1 sub-region of the hippocampus, while the neighboring CA3 sub-region is left largely intact. By studying factors pertaining to such selective vulnerability, we can develop therapies to enhance outcome after stroke. Using untargeted liquid chromatography-mass spectrometry, we analyzed temporal metabolomic changes in CA1 and CA3 hippocampal areas following tGCI in rats till the setting of neuronal apoptosis. 64 compounds in CA1 and 74 in CA3 were found to be enriched and statistically significant following tGCI. Pathway analysis showed that pyrimidine and purine metabolism pathways amongst several others to be enriched after tGCI in CA1 and CA3. Metabolomics analysis was able to capture very early changes following ischemia. We detected 6 metabolites to be upregulated and 6 to be downregulated 1 hour after tGCI in CA1 versus CA3. Several metabolites related to apoptosis and inflammation were differentially expressed in both regions after tGCI. We offer a new insight into the process of neuronal apoptosis, guided by metabolomic profiling that was not performed to such an extent previously.
安定同位体内標準物質を用いた修飾核酸一斉定量系の構築

平本航大, 渡辺匠, 松本洋太郎, 塚本宏樹, 富岡佳久

日本薬学会年会要旨集　140年会　27J-am09S　2020/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
グアニル酸シクラーゼC受容体作動薬リナクロチドは血中TMAO値を低下させ慢性腎不全に伴う心血管疾患のリスクを緩和する

原文香, 金光祥臣, 福田真嗣, 菊地晃一, 何欣蓉, 鈴木千登世, 曽我朋義, 富岡佳久, 阿部高明

日本内分泌学会雑誌　95　(4)　1612-1612　2020/02
Publisher: (一社)日本内分泌学会
ISSN： 0029-0661

eISSN： 2186-506X
フェニル硫酸は糖尿病性腎症におけるアルブミン尿増悪の新たな原因物質である

菊地晃一, 三枝大輔, 金光祥臣, 松本洋太郎, 三瀬広記, 鈴木健弘, 寳澤篤, 和田淳, 富岡佳久, 阿部高明

日本内分泌学会雑誌　95　(4)　1620-1620　2020/02
Publisher: (一社)日本内分泌学会
ISSN： 0029-0661

eISSN： 2186-506X
The guanylate cyclase C agonist linaclotide ameliorates the gut-cardio-renal axis in an adenine-induced mouse model of chronic kidney disease. International-journal Peer-reviewed

Fumika Nanto-Hara, Yoshitomi Kanemitsu, Shinji Fukuda, Koichi Kikuchi, Kei Asaji, Daisuke Saigusa, Tomoyuki Iwasaki, Hsin-Jung Ho, Eikan Mishima, Takehiro Suzuki, Chitose Suzuki, Tomoya Tsukimi, Tetsuro Matsuhashi, Yoshitsugu Oikawa, Yukako Akiyama, Shigeo Kure, Yuji Owada, Yoshihisa Tomioka, Tomoyoshi Soga, Sadayoshi Ito, Takaaki Abe

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association　35　(2)　250-264　2020/02/01

DOI： 10.1093/ndt/gfz126 　

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BACKGROUND: Cardiorenal syndrome is a major cause of mortality in patients with chronic kidney disease (CKD). However, the involvement of detrimental humoral mediators in the pathogenesis of cardiorenal syndrome is still controversial. Trimethylamine-N-oxide (TMAO), a hepatic metabolic product of trimethylamine generated from dietary phosphatidylcholine or carnitine derived by the gut microbiota, has been linked directly with progression of cardiovascular disease and renal dysfunction. Thus, targeting TMAO may be a novel strategy for the prevention of cardiovascular disease and chronic kidney disease. METHODS: Linaclotide, a guanylate cyclase C agonist, was administered to adenine-induced renal failure (RF) mice and changes in renal function and levels of gut-derived uremic toxins, as well as the gut microbiota community, were analyzed using metabolomic and metagenomic methods to reveal its cardiorenal effect. RESULTS: Linaclotide decreased the plasma levels of TMAO at a clinically used low dose of 10 μg/kg in the adenine-induced RF mouse model. At a high concentration of 100 μg/kg, linaclotide clearly improved renal function and reduced the levels of various uremic toxins. A reduction in TMAO levels following linaclotide treatment was also observed in a choline-fed pro-atherosclerotic model. Linaclotide ameliorated renal inflammation and fibrosis and cardiac fibrosis, as well as decreased the expression of collagen I, transforming growth factor-β, galectin-3 (Gal-3) and ST2 genes. Plasma levels of Gal-3 and ST2 were also reduced. Because exposure of cardiomyocytes to TMAO increased fibronectin expression, these data suggest that linaclotide reduced the levels of TMAO and various uremic toxins and may result in not only renal, but also cardiac, fibrosis. F4/80-positive macrophages were abundant in small intestinal crypts in RF mice, and this increased expression was decreased by linaclotide. Reduced colonic claudin-1 levels were also restored by linaclotide, suggesting that linaclotide ameliorated the 'leaky gut' in RF mice. Metagenomic analysis revealed that the microbial order Clostridiales could be responsible for the change in TMAO levels. CONCLUSION: Linaclotide reduced TMAO and uremic toxin levels and could be a powerful tool for the prevention and control of the cardiorenal syndrome by modification of the gut-cardio-renal axis.
Comprehensive and semi-quantitative analysis of carboxyl-containing metabolites related to gut microbiota on chronic kidney disease using 2-picolylamine isotopic labeling LC-MS/MS. International-journal Peer-reviewed

Yoshitomi Kanemitsu, Eikan Mishima, Masamitsu Maekawa, Yotaro Matsumoto, Daisuke Saigusa, Hiroaki Yamaguchi, Jiro Ogura, Hiroki Tsukamoto, Yoshihisa Tomioka, Takaaki Abe, Nariyasu Mano

Scientific reports　9　(1)　19075-19075　2019/12/13

DOI： 10.1038/s41598-019-55600-1 　

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Carboxyl-containing metabolites, such as bile acids and fatty acids, have many important functions and microbiota is involved in the production of them. In the previous study, we found that the chronic kidney disease (CKD) model mice raised under germ-free conditions provided more severe renal damage than the mice with commensal microbiota. However, the precise influence by the microbiome and carboxyl-containing metabolites to the renal functions is unknown. In this study, we aimed to develop a novel chemical isotope labeling-LC-MS/MS method using the 2-picolylamine and its isotopologue and applied the analysis of effects of microbiome and CKD pathophysiology. The developed semi-quantitative method provided the high accuracy not inferior to the absolute quantification. By comparing of four groups of mice, we found that both microbiota and renal function can alter the composition and level of these metabolites in both plasma and intestine. In particular, the intestinal level of indole-3-acetic acid, short-chain fatty acids and n-3 type of polyunsaturated fatty acid, which play important roles in the endothelial barrier function, were significantly lower in germ-free conditions mice with renal failure. Accordingly, it is suggested these metabolites might have a renoprotective effect on CKD by suppressing epithelial barrier disruption.
Structural Determination of Lysosphingomyelin-509 and Discovery of Novel Class Lipids from Patients with Niemann-Pick Disease Type C. International-journal Peer-reviewed

Masamitsu Maekawa, Isamu Jinnoh, Yotaro Matsumoto, Aya Narita, Ryuichi Mashima, Hidenori Takahashi, Anna Iwahori, Daisuke Saigusa, Kumiko Fujii, Ai Abe, Katsumi Higaki, Shosei Yamauchi, Yuji Ozeki, Kazutaka Shimoda, Yoshihisa Tomioka, Torayuki Okuyama, Yoshikatsu Eto, Kousaku Ohno, Peter T Clayton, Hiroaki Yamaguchi, Nariyasu Mano

International journal of molecular sciences　20　(20)　2019/10/10

DOI： 10.3390/ijms20205018 　

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Niemann-Pick disease type C (NPC) is an autosomal recessive disorder caused by the mutation of cholesterol-transporting proteins. In addition, early treatment is important for good prognosis of this disease because of the progressive neurodegeneration. However, the diagnosis of this disease is difficult due to a variety of clinical spectrum. Lysosphingomyelin-509, which is one of the most useful biomarkers for NPC, was applied for the rapid and easy detection of NPC. The fact that its chemical structure was unknown until recently implicates the unrevealed pathophysiology and molecular mechanisms of NPC. In this study, we aimed to elucidate the structure of lysosphingomyelin-509 by various mass spectrometric techniques. As our identification strategy, we adopted analytical and organic chemistry approaches to the serum of patients with NPC. Chemical derivatization and hydrogen abstraction dissociation-tandem mass spectrometry were used for the determination of function groups and partial structure, respectively. As a result, we revealed the exact structure of lysosphingomyelin-509 as N-acylated and O-phosphocholine adducted serine. Additionally, we found that a group of metabolites with N-acyl groups were increased considerably in the serum/plasma of patients with NPC as compared to that of other groups using targeted lipidomics analysis. Our techniques were useful for the identification of lysosphingomyelin-509.
An agonistic anti-Toll-like receptor 4 monoclonal antibody as an effective adjuvant for cancer immunotherapy. International-journal Peer-reviewed

Hiroki Tsukamoto, Kanae Kubota, Ayumi Shichiku, Masamitsu Maekawa, Nariyasu Mano, Hideo Yagita, Shoichiro Ohta, Yoshihisa Tomioka

Immunology　158　(2)　136-149　2019/10

DOI： 10.1111/imm.13095 　

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Immune-checkpoint blockade antibodies have been approved for the treatment of cancer. However, poorly immunogenic tumours are less responsive to such therapies. Agonistic anti-Toll-like receptor 4 (TLR4) monoclonal antibodies (mAbs) activate only cell-surface TLR4; in contrast, lipopolysaccharide (LPS) activates both TLR4 and intracellular inflammatory caspases. In this study, we investigated the adjuvant activity of an anti-TLR4 mAb in T-cell-mediated antitumour immunity. The anti-TLR4 mAb induced the activation of antigen-specific T-cells in adoptive transfer studies. The growth of ovalbumin (OVA)-expressing tumours was significantly suppressed by administration of OVA and the anti-TLR4 mAb in combination, but not individually. The antitumour effect of anti-PD-1 mAb was enhanced in mice administered with OVA plus the anti-TLR4 mAb. The OVA-specific IFN-γ-producing CD8 T-cells were induced by administration of OVA and the anti-TLR4 mAb. The suppression of tumour growth was diminished by depletion of CD8, but not CD4, T-cells. The inflammatory response to the anti-TLR4 mAb was of significantly lesser magnitude than that to LPS, as assessed by NF-κB activation and production of TNF-α, IL-6 and IL-1β. Administration of LPS (at a dose that elicited levels of proinflammatory cytokines comparable to those by the anti-TLR4 mAb) plus OVA induced no or less-marked activation of OVA-specific T-cells and failed to suppress tumour growth in mice. In conclusion, the agonistic anti-TLR4 mAb induces potent CD8 T-cell-dependent antitumour immunity and an inflammatory response of lesser magnitude than does LPS. The agonistic anti-TLR4 mAb has potential as an adjuvant for use in vaccines against cancer.
ミエロイド由来抑制細胞を介したToll様受容体4によるリンパ球抗原特異的免疫応答の抑制機序

塚本宏樹, 小坂井沙緒, 小林洋平, 高梨理紗子, 青柳拓哉, 富岡佳久

日本生化学会大会プログラム・講演要旨集　92回　[2T16a-05]　2019/09
Publisher: (公社)日本生化学会
Identification of novel biomarkers of hepatocellular carcinoma by high-definition mass spectrometry: Ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry and desorption electrospray ionization mass spectrometry imaging. International-journal Peer-reviewed

Koshi Nagai, Baasanjav Uranbileg, Zhen Chen, Amane Fujioka, Takahiro Yamazaki, Yotaro Matsumoto, Hiroki Tsukamoto, Hitoshi Ikeda, Yutaka Yatomi, Hitoshi Chiba, Shu-Ping Hui, Toru Nakazawa, Ritsumi Saito, Seizo Koshiba, Junken Aoki, Daisuke Saigusa, Yoshihisa Tomioka

Rapid communications in mass spectrometry : RCM　34 Suppl 1　(Suppl 1)　e8551　2019/08/14

DOI： 10.1002/rcm.8551 　

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RATIONALE: Hepatocellular carcinoma (HCC) is a highly malignant disease for which the development of prospective or prognostic biomarkers is urgently required. Although metabolomics is widely used for biomarker discovery, there are some bottlenecks regarding the comprehensiveness of detected features, reproducibility of methods, and identification of metabolites. In addition, information on localization of metabolites in tumor tissue is needed for functional analysis. Here, we developed a wide-polarity global metabolomics (G-Met) method, identified HCC biomarkers in human liver samples by high-definition mass spectrometry (HDMS), and demonstrated localization in cryosections using desorption electrospray ionization MS imaging (DESI-MSI) analysis. METHODS: Metabolic profiling of tumor (n = 38) and nontumor (n = 72) regions in human livers of HCC was performed by an ultrahigh-performance liquid chromatography quadrupole time-of-flight MS (UHPLC/QTOFMS) instrument equipped with a mixed-mode column. The HCC biomarker candidates were extracted by multivariate analyses and identified by matching values of the collision cross section and their fragment ions on the mass spectra obtained by HDMS. Cryosections of HCC livers, which included both tumor and nontumor regions, were analyzed by DESI-MSI. RESULTS: From the multivariate analysis, m/z 904.83 and m/z 874.79 were significantly high and low, respectively, in tumor samples and were identified as triglyceride (TG) 16:0/18:1(9Z)/20:1(11Z) and TG 16:0/18:1(9Z)/18:2(9Z,12Z) using the synthetic compounds. The TGs were clearly localized in the tumor or nontumor areas of the cryosection. CONCLUSIONS: Novel biomarkers for HCC were identified by a comprehensive and reproducible G-Met method with HDMS using a mixed-mode column. The combination analysis of UHPLC/QTOFMS and DESI-MSI revealed that the different molecular species of TGs were associated with tumor distribution and were useful for characterizing the progression of tumor cells and discovering prospective biomarkers.
Identification of novel biomarkers of hepatocellular carcinoma by a high definition mass spectrometry; UHPLC-QTOF/MS and DESI-MSI. Peer-reviewed

Nagai K, Uranbileg B, Chen Z, Fujioka A, Yamazaki T, Matsmoto Y, Tsukamoto H, Ikeda H, Yatomi Y, Chiba H, Hui SP, Nakazawa T, Saito R, Koshiba S, Aoki J, Saigusa D, Tomioka Y

Rapid communications in mass spectrometry : RCM　2019/08

DOI： 10.1002/rcm.8551 　

ISSN： 0951-4198
グアニル酸シクラーゼC受容体作動薬リナクロチドは慢性腎不全に伴う心血管疾患のリスクを緩和する

原文香[南都], 金光祥臣, 福田真嗣, 何欣蓉, 菊地晃一, 鈴木千登世, 曽我朋義, 富岡佳久, 伊藤貞嘉, 阿部高明

日本腎臓学会誌　61　(3)　312-312　2019/05
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
ケモカインレセプターCCR10阻害薬による腎不全抑制効果の検討

一條真梨子, 何欣蓉, 金光祥臣, 菊地晃一, 秋山由雅子, 三島英換, 鈴木健弘, 鈴木千登世, 富岡佳久, 伊藤貞嘉, 阿部高明

日本腎臓学会誌　61　(3)　325-325　2019/05
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
Impaired antigen-specific lymphocyte priming in mice after Toll-like receptor 4 activation via induction of monocytic myeloid-derived suppressor cells. International-journal Peer-reviewed

Hiroki Tsukamoto, Sao Kozakai, Yohei Kobayashi, Risako Takanashi, Takuya Aoyagi, Muneo Numasaki, Shoichiro Ohta, Yoshihisa Tomioka

European journal of immunology　49　(4)　546-563　2019/04

DOI： 10.1002/eji.201847805 　

ISSN： 0014-2980

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In sepsis, the pathology involves a shift from a proinflammatory state toward an immunosuppressive phase. We previously showed that an agonistic anti-TLR4 antibody induced long-term endotoxin tolerance and suppressed antigen-specific secondary IgG production when primed prior to immunization with antigen. These findings led us to speculate that TLR4-induced innate tolerance due to primary infection causes an immunosuppressive pathology in sepsis. Therefore, the mechanism underlying impaired antigen-specific humoral immunity by the TLR4 antibody was investigated. We showed, in a mouse model, that primary antigen-specific IgG responses were impaired in TLR4 antibody-induced tolerized mice, which was the result of reduced numbers of antigen-specific GC B cells and plasma cells. Ovalbumin-specific CD4 and CD8 T-cell responses were impaired in TLR4 antibody-injected OT-I and -II transgenic mice ex vivo. Adoptive transfer studies demonstrated suppression of OVA-specific CD4 and CD8 T-cell responses by the TLR4 antibody in vivo. The TLR4 antibody induced Gr1+ CD11b+ myeloid-derived suppressor cell (MDSC) expansion with suppression of T-cell activation. Monocytic MDSCs were more suppressive and exhibited higher expression of PD-L1 and inducible nitric oxidase compared with granulocytic MDSCs. In conclusion, immune tolerance conferred by TLR4 activation induces the expansion of monocytic MDSCs, which impairs antigen-specific T-cell priming and IgG production.
Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease. International-journal Peer-reviewed

Kikuchi K, Saigusa D, Kanemitsu Y, Matsumoto Y, Thanai P, Suzuki N, Mise K, Yamaguchi H, Nakamura T, Asaji K, Mukawa C, Tsukamoto H, Sato T, Oikawa Y, Iwasaki T, Oe Y, Tsukimi T, Fukuda NN, Ho HJ, Nanto-Hara F, Ogura J, Saito R, Nagao S, Ohsaki Y, Shimada S, Suzuki T, Toyohara T, Mishima E, Shima H, Akiyama Y, Akiyama Y, Ichijo M, Matsuhashi T, Matsuo A, Ogata Y, Yang CC, Suzuki C, Breeggemann MC, Heymann J, Shimizu M, Ogawa S, Takahashi N, Suzuki T, Owada Y, Kure S, Mano N, Soga T, Wada T, Kopp JB, Fukuda S, Hozawa A, Yamamoto M, Ito S, Wada J, Tomioka Y, Abe T

Nature communications　10　(1)　1835-1835　2019/04

DOI： 10.1038/s41467-019-09735-4 　

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Diabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Here we show using untargeted metabolomics that levels of phenyl sulfate, a gut microbiota-derived metabolite, increase with the progression of diabetes in rats overexpressing human uremic toxin transporter SLCO4C1 in the kidney, and are decreased in rats with limited proteinuria. In experimental models of diabetes, phenyl sulfate administration induces albuminuria and podocyte damage. In a diabetic patient cohort, phenyl sulfate levels significantly correlate with basal and predicted 2-year progression of albuminuria in patients with microalbuminuria. Inhibition of tyrosine phenol-lyase, a bacterial enzyme responsible for the synthesis of phenol from dietary tyrosine before it is metabolized into phenyl sulfate in the liver, reduces albuminuria in diabetic mice. Together, our results suggest that phenyl sulfate contributes to albuminuria and could be used as a disease marker and future therapeutic target in diabetic kidney disease.
Toll様受容体4刺激抗体によるアレルギー性接触皮膚炎抑制効果

紫竹歩, 塚本宏樹, 渡邊康一, 野地智法, 麻生久, 富岡佳久

日本薬学会年会要旨集　139年会　(3)　110-110　2019/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
Canagliflozin reduces plasma uremic toxins and alters the intestinal microbiota composition in a chronic kidney disease mouse model Peer-reviewed

†Mishima, E, †Fukuda, S, Contributed equally to this work, Kanemitsu, Y, Saigusa, D, Mukawa, C, Asaji, K, Matsumoto, Y, Tsukamoto, H, Tachikawa, T, Tsukimi, T, Fukuda, N, Ho, HJ., Kikuchi, K. Suzuki, C, Nanto, F, Suzuki, T, Ito, S, Soga, T, Tomioka, Y, Abe, T

Am. J. Physiol. Renal. Physiol.　315　(4)　F824-F833-F833　2018/10/01
Publisher: American Journal of Physiology - Renal Physiology
ISSN： 0363-6127

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© 2018 the American Physiological Society. Mishima E, Fukuda S, Kanemitsu Y, Saigusa D, Mukawa C, Asaji K, Matsumoto Y, Tsukamoto H, Tachikawa T, Tsukimi T, Fukuda NN, Ho HJ, Kikuchi K, Suzuki C, Nanto F, Suzuki T, Ito S, Soga T, Tomioka Y, Abe T. Canagliflozin reduces plasma uremic toxins and alters the intestinal microbiota composition in a chronic kidney disease mouse model. Am J Physiol Renal Physiol 315: F824–F833, 2018. First published November 22, 2017; doi:10.1152/ajprenal.00314.2017.—Accumulation of uremic toxins, which exert deleterious effects in chronic kidney disease, is influenced by the intestinal environment; the microbiota contributes to the production of representative uremic toxins, including p-cresyl sulfate and indoxyl sulfate. Canagliflozin is a sodium-glucose cotransporter (SGLT) 2 inhibitor, and it also exerts a modest inhibitory effect on SGLT1. The inhibition of intestinal SGLT1 can influence the gastrointestinal environment. We examined the effect of canagliflozin on the accumulation of uremic toxins in chronic kidney disease using adenine-induced renal failure mice. Two-week canagliflozin (10 mg/kg po) treatment did not influence the impaired renal
Canagliflozin reduces plasma uremic toxins and alters the intestinal microbiota composition in a chronic kidney disease mouse model. International-journal Peer-reviewed

Mishima E, Fukuda S, Kanemitsu Y, Saigusa D, Mukawa C, Asaji K, Matsumoto Y, Tsukamoto H, Tachikawa T, Tsukimi T, Fukuda NN, Ho HJ, Kikuchi K, Suzuki C, Nanto F, Suzuki T, Ito S, Soga T, Tomioka Y, Abe T

American journal of physiology. Renal physiology　315　(4)　F824-F833　2018/10

DOI： 10.1152/ajprenal.00314.2017 　

ISSN： 1931-857X
Toll様受容体4刺激抗体による抗腫瘍T細胞誘導を介したがん免疫療法

塚本宏樹, 久保田佳苗, 富岡佳久

日本生化学会大会プログラム・講演要旨集　91回　[1P-273]　2018/09
Publisher: (公社)日本生化学会
Detection of novel metabolite for roxadustat doping by global metabolomics. International-journal Peer-reviewed

Saigusa D, Suzuki N, Matsumoto Y, Umeda K, Tomioka Y, Koshiba S, Yamamoto M

Journal of biochemistry　163　(6)　e1　2018/06

DOI： 10.1093/jb/mvy036 　

ISSN： 0021-924X
Lipopolysaccharide (LPS)-binding protein stimulates CD14-dependent Toll-like receptor 4 internalization and LPS-induced TBK1-IKKϵ-IRF3 axis activation. International-journal Peer-reviewed

Tsukamoto H, Takeuchi S, Kubota K, Kobayashi Y, Kozakai S, Ukai I, Shichiku A, Okubo M, Numasaki M, Kanemitsu Y, Matsumoto Y, Nochi T, Watanabe K, Aso H, Tomioka Y

The Journal of biological chemistry　293　(26)　10186-10201　2018/06

DOI： 10.1074/jbc.M117.796631 　

ISSN： 0021-9258

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Toll-like receptor 4 (TLR4) is an indispensable immune receptor for lipopolysaccharide (LPS), a major component of the Gram-negative bacterial cell wall. Following LPS stimulation, TLR4 transmits the signal from the cell surface and becomes internalized in an endosome. However, the spatial regulation of TLR4 signaling is not fully understood. Here, we investigated the mechanisms of LPS-induced TLR4 internalization and clarified the roles of the extracellular LPS-binding molecules, LPS-binding protein (LBP), and glycerophosphatidylinositol-anchored protein (CD14). LPS stimulation of CD14-expressing cells induced TLR4 internalization in the presence of serum, and an inhibitory anti-LBP mAb blocked its internalization. Addition of LBP to serum-free cultures restored LPS-induced TLR4 internalization to comparable levels of serum. The secretory form of the CD14 (sCD14) induced internalization but required a much higher concentration than LBP. An inhibitory anti-sCD14 mAb was ineffective for serum-mediated internalization. LBP lacking the domain for LPS transfer to CD14 and a CD14 mutant with reduced LPS binding both attenuated TLR4 internalization. Accordingly, LBP is an essential serum molecule for TLR4 internalization, and its LPS transfer to membrane-anchored CD14 (mCD14) is a prerequisite. LBP induced the LPS-stimulated phosphorylation of TBK1, IKKϵ, and IRF3, leading to IFN-β expression. However, LPS-stimulated late activation of NF-κB or necroptosis were not affected. Collectively, our results indicate that LBP controls LPS-induced TLR4 internalization, which induces TLR adaptor molecule 1 (TRIF)-dependent activation of the TBK1-IKKϵ-IRF3-IFN-β pathway. In summary, we showed that LBP-mediated LPS transfer to mCD14 is required for serum-dependent TLR4 internalization and activation of the TRIF pathway.
The Disease-modifying Drug Candidate, SAK3 Improves Cognitive Impairment and Inhibits Amyloid beta Deposition in App Knock-in Mice. International-journal Peer-reviewed

Hisanao Izumi, Yasuharu Shinoda, Takashi Saito, Takaomi C Saido, Keita Sato, Yasushi Yabuki, Yotaro Matsumoto, Yoshitomi Kanemitsu, Yoshihisa Tomioka, Nona Abolhassani, Yusaku Nakabeppu, Kohji Fukunaga

Neuroscience　377　87-97　2018/05/01

DOI： 10.1016/j.neuroscience.2018.02.031 　

ISSN： 0306-4522

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Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common form of elderly dementia in the world. At present, acetylcholine inhibitors, such as donepezil, galantamine and rivastigmine, are used for AD therapy, but the therapeutic efficacy is limited. We recently proposed T-type voltage-gated Ca2+ channels' (T-VGCCs) enhancer as a new therapeutic candidate for AD. In the current study, we confirmed the pharmacokinetics of SAK3 in the plasma and brain of mice using ultra performance liquid chromatography-tandem mass spectrometry. We also investigated the effects of SAK3 on the major symptoms of AD, such as cognitive dysfunction and amyloid beta (Aβ) accumulation, in AppNL-F knock-in (NL-F) mice, which have been established as an AD model. Chronic SAK3 (0.5 mg/kg/day) oral administration for 3 months from 9 months of age improved cognitive function and inhibited Aβ deposition in 12-month-old NL-F mice. Using microarray and real-time PCR analysis, we discovered serum- and glucocorticoid-induced protein kinase 1 (SGK1) as one of possible genes involved in the inhibition of Aβ deposition and improvement of cognitive function by SAK3. These results support the idea that T-VGCC enhancer, SAK3 could be a novel candidate for disease-modifying therapeutics for AD.
グアニル酸シクラーゼC受容体作動薬リナクロチドは腎不全に伴う腸内環境悪性化を改善し腎線維化を抑制する

南都文香, 福田真嗣, 金光祥臣, 三枝大輔, 菊地晃一, 何欣蓉, 三島英換, 鈴木健弘, 松橋徹郎, 及川義嗣, 鈴木千登世, 富岡佳久, 曽我朋義, 伊藤貞嘉, 阿部高明

日本腎臓学会誌　60　(3)　463-463　2018/04
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
Detection of novel metabolite for Roxadustat doping by global metabolomics. International-journal Peer-reviewed

Saigusa D, Suzuki N, Matsumoto Y, Umeda K, Tomioka Y, Koshiba S, Yamamoto M

Journal of biochemistry　2018/02

DOI： 10.1093/jb/mvy028 　

ISSN： 0021-924X

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Roxadustat (FG-4592, Rox) is a stabilizer for hypoxia-inducible transcription factors (HIFs), which induce production of the erythroid growth factor erythropoietin, and has been listed by the World Anti-Doping Agency as a prohibited substance for athletes since 2011. Although the detection technologies for Rox and its glucuronide-conjugated metabolite (Rox-Gluc) have been developed exploiting triple quadrupole mass spectrometry (MS/MS), the production of metabolites from Rox in the human body remains to be clarified. Here, we established a protocol for the detection of unknown metabolites in plasma and urine samples from Rox-doping mice by global metabolomics using an ultra high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). We identified methylated Rox (Rox-Methyl), a novel metabolite, and Rox-Gluc in mouse urine by principal component analysis and orthogonal partial least squares discriminant analysis based on detected features by UHPLC-QTOF/MS analysis. The estimated pharmacokinetic parameters of Rox-Methyl and Rox-Gluc in mouse plasma showed similar profiles to that of Rox and both compounds showed similar biological activities. Of note, Rox-Methyl showed shorter half-life than Rox-Gluc in vivo, implying the easy escape from anti-doping screen. These results demonstrate that the global metabolomics method introduced in this study will contribute to the identification and detection of HIF-analog doping.
Generation and Characterization of Anti-phenyl Sulfate Monoclonal Antibodies and a Potential Use for Phenyl Sulfate Analysis in Human Blood. Peer-reviewed

Kanemitsu Y, Tsukamoto H, Matsumoto Y, Nozawa-Kumada K, Kondo Y, Abe T, Tomioka Y

Biological & pharmaceutical bulletin　41　(8)　1170-1177　2018

DOI： 10.1248/bpb.b17-00925 　

ISSN： 0918-6158

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Patients with chronic kidney disease (CKD) have increased blood levels of phenyl sulfate (PS), a circulating uremic toxin. In this study, we produced anti-PS monoclonal antibodies (mAbs) and characterized their cross-reactivity to structural PS analogs. To induce PS-specific mAbs, we synthesized 4-mercaptophenyl sulfate with a sulfhydryl group at the para-position of PS and conjugated it to carrier proteins via bifunctional linkers. Using these PS conjugates as immunogens and as antigens for enzyme-linked immunosorbent assay (ELISA) screening, we produced by a hybridoma method two novel mAbs (YK33.1 and YKS19.2) that react with PS conjugates independent of carrier and linker structures. Although all of the PS analogs tested, with the exception of indoxyl sulfate, were cross-reactive to both mAbs in phosphate buffered saline (PBS), PS specificity for YKS19.2 was enhanced in human plasma and serum. YKS19.2 mAb was cross-reactive only with o-cresyl sulfate, which is absent in human blood. PS sensitivity for YKS19.2 mAb increased to an IC50 of 10.4 µg/mL when 0.1% Tween 20 was added in a primary competitive reaction. To explore potential clinical applications, we determined concentrations of PS in serum samples from 19 CKD patients by inhibition ELISA using YKS19.2 mAb and compared them to those found using an LC-MS/MS method. A good correlation was observed between each value (R2=0.825). Therefore, the unique antigen specificity of YKS19.2 mAb could be useful for prescreening of patients with accumulated PS or for comprehensive analysis of uremic toxins that have a PS-like structure.
Impact of the Oral Adsorbent AST-120 on Organ-Specific Accumulation of Uremic Toxins: LC-MS/MS and MS Imaging Techniques. Peer-reviewed

Sato E, Saigusa D, Mishima E, Uchida T, Miura D, Morikawa-Ichinose T, Kisu K, Sekimoto A, Saito R, Oe Y, Matsumoto Y, Tomioka Y, Mori T, Takahashi N, Sato H, Abe T, Niwa T, Ito S

Toxins　10　(1)　19-19　2017/12
Publisher: MDPI AG
DOI： 10.3390/toxins10010019 　

eISSN： 2072-6651
A novel indole compound MA-35 attenuates renal fibrosis by inhibiting both TNF-α and TGF-β1 pathways Peer-reviewed

Hisato Shima, Kensuke Sasaki, Takehiro Suzuki, Chikahisa Mukawa, Ten Obara, Yuki Oba, Akihiro Matsuo, Takayasu Kobayashi, Eikan Mishima, Shun Watanabe, Yasutoshi Akiyama, Koichi Kikuchi, Tetsuro Matsuhashi, Yoshitsugu Oikawa, Fumika Nanto, Yukako Akiyama, Hsin-Jung Ho, Chitose Suzuki, Daisuke Saigusa, Atsushi Masamune, Yoshihisa Tomioka, Takao Masaki, Sadayoshi Ito, Ken-Ichiro Hayashi, Takaaki Abe

Scientific Reports　7　(1)　2017/12/01

DOI： 10.1038/s41598-017-01702-7 　

ISSN： 2045-2322
Simultaneous quantitative analysis of uremic toxins by LC MS/MS with a reversed-phase/cation-exchange/anion-exchange tri-modal mixed-mode column Peer-reviewed

Yoshitomi Kanemitsu, Kei Asaji, Yotaro Matsumoto, Hiroki Tsukamoto, Daisuke Saigusa, Chikahisa Mukawa, Tatsuki Tachikawa, Takaaki Abe, Yoshihisa Tomioka

JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES　1068　1-8　2017/11

DOI： 10.1016/j.jchromb.2017.10.009 　

ISSN： 1570-0232

eISSN： 1873-376X
Ginsenoside Rg1 alleviates corticosterone-induced dysfunction of gap junctions in astrocytes Peer-reviewed

Cong-Yuan Xia, Shi-Feng Chu, Shuai Zhang, Yan Gao, Qian Ren, Yu-Xia Lou, Piao Luo, Man-Tong Tian, Zhi-Qi Wang, Guo-Hua Du, Yoshihisa Tomioka, Tohru Yamakuni, Yi Zhang, Zhen-Zhen Wang, Nai-Hong Chen

JOURNAL OF ETHNOPHARMACOLOGY　208　207-213　2017/09

DOI： 10.1016/j.jep.2017.06.031 　

ISSN： 0378-8741
An inhibitory epitope of human Toll-like receptor 4 resides on leucine-rich repeat 13 and is recognized by a monoclonal antibody. International-journal Peer-reviewed

Tsukamoto H, Yamagata Y, Ukai I, Takeuchi S, Okubo M, Kobayashi Y, Kozakai S, Kubota K, Numasaki M, Kanemitsu Y, Matsumoto Y, Tomioka Y

FEBS letters　591　(18)　2953-2953　2017/09

DOI： 10.1002/1873-3468.12837 　

ISSN： 0014-5793
Evaluation of the impact of gut microbiota on uremic solute accumulation by a CE-TOFMS-based metabolomics approach Peer-reviewed

Eikan Mishima, Shinji Fukuda, Chikahisa Mukawa, Akinori Yuri, Yoshitomi Kanemitsu, Yotaro Matsumoto, Yasutoshi Akiyama, Noriko N. Fukuda, Hiroki Tsukamoto, Kei Asaji, Hisato Shima, Koichi Kikuchi, Chitose Suzuki, Takehiro Suzuki, Yoshihisa Tomioka, Tomoyoshi Soga, Sadayoshi Ito, Takaaki Abe

KIDNEY INTERNATIONAL　92　(3)　634-645　2017/09

DOI： 10.1016/j.kint.2017.02.011 　

ISSN： 0085-2538

eISSN： 1523-1755
An inhibitory epitope of human Toll-like receptor 4 resides on leucine-rich repeat 13 and is recognized by a monoclonal antibody. International-journal Peer-reviewed

Tsukamoto H, Yamagata Y, Ukai I, Takeuchi S, Okubo M, Kobayashi Y, Kozakai S, Kubota K, Numasaki M, Kanemitsu Y, Matsumoto Y, Tomioka Y

FEBS letters　591　(16)　2406-2416　2017/08

DOI： 10.1002/1873-3468.12768 　

ISSN： 0014-5793

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Lipopolysaccharide (LPS)-induced activation of Toll-like receptor 4 (TLR4) elicits the innate immune response and can trigger septic shock if excessive. Two antibodies (HT4 and HT52) inhibit LPS-induced human TLR4 activation via novel LPS binding-independent mechanisms. The HT52 epitope resides on leucine-rich repeat 2 (LRR2) and is a feature of many inhibitory antibodies; antigen specificity of HT4 does not reside in LRR2. Here, we identified an HT4 epitope on LRR13 located close to the TLR4 dimerization interface that plays a role in NFκB activation. HT4 and HT52 mutually enhanced TLR4 inhibition. LRR13 is a novel inhibitory epitope and may be useful for developing anti-TLR4 antibodies. Combination therapy with LRR2 and LRR13 may effectively inhibit TLR4 activation.
An inhibitory epitope of human Toll-like receptor 4 resides on leucine-rich repeat 13 and is recognized by a monoclonal antibody Peer-reviewed

Hiroki Tsukamoto, Yuki Yamagata, Ippo Ukai, Shino Takeuchi, Misaki Okubo, Yohei Kobayashi, Sao Kozakai, Kanae Kubota, Muneo Mumasaki, Yoshitomi Kanemitsu, Yotaro Matsumoto, Yoshihisa Tomioka

FEBS LETTERS　591　(16)　2406-2416　2017/08

DOI： 10.1002/1873-3468.12768 　

ISSN： 1873-3468
Mitochonic Acid 5 (MA-5) Facilitates ATP Synthase Oligomerization and Cell Survival in Various Mitochondrial Diseases Peer-reviewed

Tetsuro Matsuhashi, Takeya Sato, Shin-ichiro Kanno, Takehiro Suzuki, Akihiro Matsuo, Yuki Oba, Motoi Kikusato, Emi Ogasawara, Tai Kudo, Kosuke Suzuki, Osamu Ohara, Hiroko Shimbo, Fumika Nanto, Hiroaki Yamaguchi, Daisuke Saigusa, Yasuno Mukaiyama, Akiko Watabe, Koichi Kikuchi, Hisato Shima, Eikan Mishima, Yasutoshi Akiyama, Yoshitsugu Oikawa, Hsin-Jung Ho, Yukako Akiyama, Chitose Suzuki, Mitsugu Uematsu, Masaki Ogata, Naonori Kumagai, Masaaki Toyomizu, Atsushi Hozawa, Nariyasu Mano, Yuji Owada, Setsuya Aiba, Teruyuki Yanagisawa, Yoshihisa Tomioka, Shigeo Kure, Sadayoshi Ito, Kazuto Nakada, Ken-ichiro Hayashi, Hitoshi Osaka, Takaaki Abe

EBIOMEDICINE　20　27-38　2017/06

DOI： 10.1016/j.ebiom.2017.05.016 　

ISSN： 2352-3964
服薬アセスメント指標の現状と確立の必要性

村井ユリ子, 赤坂和俊, 小原拓, 木皿重樹, 佐藤真由美, 久道周彦, 松浦正樹, 山口浩明, 佐藤博, 富岡佳久, 眞野成康

日本薬学会年会要旨集　137年会　(4)　150-150　2017/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
Licochalcones extracted from Glycyrrhiza inflata inhibit platelet aggregation accompanied by inhibition of COX-1 activity Peer-reviewed

Asa Okuda-Tanino, Daiki Sugawara, Takumi Tashiro, Masaya Iwashita, Yutaro Obara, Takahiro Moriya, Chisato Tsushima, Daisuke Saigusa, Yoshihisa Tomioka, Kuniaki Ishii, Norimichi Nakahata

PLOS ONE　12　(3)　2017/03

DOI： 10.1371/journal.pone.0173628 　

ISSN： 1932-6203
V-1/CP complex formation is required for genetic co-regulation of adult nigrostriatal dopaminergic function via the RHO/MAL/SRF pathway in vitro and in vivo Peer-reviewed

Kawahata I, Lai Y, Morita J, Kato S, Ohtaku S, Tomioka Y, Tabuchi A, Tsuda M, Sumi-Ichinose C, Kondo K, Izumi Y, Kume T, Akaike A, Ohashi K, Mizuno K, Hasegawa K, Ichinose H, Kobayashi K, Yamakuni T

Journal of the Neurological Sciences　381　359-360　2017

DOI： 10.1016/j.jns.2017.08.1021 　
Rapid and selective simultaneous quantitative analysis of modified nucleosides using multi-column liquid chromatography-tandem mass spectrometry Peer-reviewed

Jinno Daisuke, Kanemitsu Yoshitomi, Saitoh Kazuki, Nankumo Shinnosuke, Tsukamoto Hiroki, Matsumoto Yotaro, Abe Takaaki, Tomioka Yoshihisa

JOURNAL OF ANALYTICAL SCIENCE AND TECHNOLOGY　8　2017

DOI： 10.1186/s40543-017-0110-4 　

ISSN： 2093-3134

eISSN： 2093-3371
Tyrosine hydroxylase gene expression is facilitated by alcohol followed by the degradation of the protein by ubiquitin proteasome system Peer-reviewed

Ichiro Kawahata, Gutierrez Rico Evelyn, Xu Huinan, Shiori Ohtaku, Yoshihisa Tomioka, Tohru Yamakuni

NEUROENDOCRINOLOGY LETTERS　38　(1)　43-49　2017

ISSN： 0172-780X
A Heterodimeric Cytokine, Consisting of IL-17A and IL-17F, Promotes Migration and Capillary-Like Tube Formation of Human Vascular Endothelial Cells Peer-reviewed

Muneo Numasaki, Hiroki Tsukamoto, Yoshihisa Tomioka, Yasuhiko Nishioka, Takashi Ohrui

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　240　(1)　47-56　2016/09

DOI： 10.1620/tjem.240.47 　

ISSN： 0040-8727

eISSN： 1349-3329
Anti-tumor immunity elicited by direct intratumoral administration of a recombinant adenovirus expressing either IL-28A/IFN-λ2 or IL-29/IFN-λ1. Peer-reviewed

K Hasegawa, M Tagawa, K Takagi, H Tsukamoto, Y Tomioka, T Suzuki, Yasuhiko Nishioka, T Ohrui, M Numasaki

Cancer Gene Therapy　Vol.23　(No.8)　266-277　2016/08/19
Publisher: Springer Science and Business Media LLC
DOI： 10.1038/cgt.2016.29 　

ISSN： 1476-5500

eISSN： 1476-5500

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Interleukin (IL)-28A/interferon (IFN)-λ2 and IL-29/IFN-λ1 have been demonstrated to elicit direct and indirect anti-tumor actions. In this study, we constructed an adenovirus vector expressing either IL-28A/IFN-λ2 (AdIL-28A) or IL-29/IFN-λ1 (AdIL-29) to evaluate the therapeutic properties of intratumoral injection of recombinant adenovirus to apply for the clinical implementation of cancer gene therapy. Despite the lack of an anti-proliferative effect on MCA205 and B16-F10 cells, a retarded growth of established subcutaneous tumors was observed following multiple injections of either AdIL-28A or AdIL-29 when compared with AdNull. In vivo cell depletion experiments displayed that both NK cells and CD8(+) T cells have a major role in AdIL-28A-mediated tumor growth suppression. A significant increase in the number of infiltrating CD8(+) T cells into the tumors treated with either AdIL-28A or AdIL-29 was observed. Moreover, specific anti-tumor cytotoxic T lymphocyte reactivity was detected in spleen cells from animals treated with either AdIL-28A or AdIL-29. In IFN-γ-deficient mice, anti-tumor activities of AdIL-28A were completely impaired, indicating that IFN-γ is critically involved in the tumor growth inhibition triggered by AdIL-28A. IL-12 provided a synergistic anti-tumor effect when combined with AdIL-28A. These results indicate that AdIL-28A and AdIL-29 could be successfully utilized as an alternative cancer immunogene therapy.
Anti-tumor immunity elicited by direct intratumoral administration of a recombinant adenovirus expressing either IL-28A/IFN-λ2 or IL-29/IFN-λ1 Peer-reviewed

Hasegawa Kei, Tagawa Masatoshi, Takagi Kiyoshi, Tsukamoto Hiroki, Tomioka Yoshihisa, Suzuki Takashi, Nishioka Yasuhiko, Ohrui Takashi, Numasaki Mueno

CANCER GENE THERAPY　23　(8)　266-277　2016/08
Publisher: Springer Science and Business Media LLC
DOI： 10.1038/cgt.2016.29 　

ISSN： 0929-1903

eISSN： 1476-5500
Mitochonic Acid 5 Binds Mitochondria and Ameliorates Renal Tubular and Cardiac Myocyte Damage Peer-reviewed

Takehiro Suzuki, Hiroaki Yamaguchi, Motoi Kikusato, Osamu Hashizume, Satoru Nagatoishi, Akihiro Matsuo, Takeya Sato, Tai Kudo, Tetsuro Matsuhashi, Kazutaka Murayanna, Yuki Ohba, Shun Watanabe, Shin-ichiro Kanno, Daichi Minaki, Daisuke Saigusa, Hiroko Shinbo, Nobuyoshi Mori, Akinori Yuri, Miyuki Yokoro, Eikan Mishima, Hisato Shima, Yasutoshi Akiyama, Yoichi Takeuchi, Koichi Kikuchi, Takafumi Toyohara, Chitose Suzuki, Takaharu Ichimura, Jun-ichi Anzai, Masahiro Kohzuki, Nariyasu Mario, Shigeo Kure, Teruyuki Yanagisawa, Yoshihisa Tomioka, Masaaki Toyomizu, Kohei Tsumoto, Kazuto Nakada, Joseph V. Bonventre, Sadayoshi Ito, Hitoshi Osaka, Ken-ichi Hayashi, Takaaki Abe

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　27　(7)　1925-1932　2016/07

DOI： 10.1681/ASN.2015060623 　

ISSN： 1046-6673

eISSN： 1533-3450
イナビル添加乳糖中のβ-ラクトグロブリンおよびその糖鎖付加体が原因と推察されたアナフィラキシーの1例

森川みき, 金光祥臣, 塚本宏樹, 森川昭正, 富岡佳久

アレルギー　65　(3)　200-205　2016/05
Publisher: (一社)日本アレルギー学会
ISSN： 0021-4884

eISSN： 1347-7935
[A CASE OF ANAPHYLAXIS IN THE PEDIATRIC PATIENT WITH MILK ALLERGY DUE TO TRACES OF MILK PROTEIN IN THE LACTOSE USED AS AN EXCIPIENT OF INAVIR INHALATION]. Peer-reviewed

Morikawa M, Kanemitsu Y, Tsukamoto H, Morikawa A, Tomioka Y

Arerugi = [Allergy]　65　(3)　200-205　2016/05

DOI： 10.15036/arerugi.65.200 　

ISSN： 0021-4884

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The patient was a 6-year-old female with milk allergy and persistent asthma. She experienced anaphylactic reactions just after the inhalation of Inavir (Laninamivir Octanoate Hydrate) to treat flu infection. A skin-prick test showed positive reactions for Inavir inhaler powder and lactose used as an excipient but negative for Laninamivir. Same results were obtained in a drug-stimulated basophil activation test. The lactose excipient in Inavir inhaler powder was supposed to contain milk proteins, which caused anaphylactic reactions. To test this possibility, we examined the contamination of allergic milk proteins in the lactose excipient and found the smear band by silver staining, which was identified as β-lactoglobulin (β-LG) by Western blotting using specific monoclonal antibody and patient's sera. The β-LG in Inavir was supposed to be glycosylated with lactose because the molecular weight was slightly higher than β-LG standard reference as seen in mobility. In fact, the incubation with lactose in vitro tended to increase molecular weight. Following these results, we herein report that the trace amounts of β-LG contaminated in the lactose excipient of Inavir could cause immediate allergic reactions. The risk that the lactose-containing dry powder inhalers cause allergic reactions for patients with cow's milk allergy need to be reminded. In particular, the use for flu patients should be paid careful attention because of increased airway hypersensitivity in those patients.
Immunogenetherapy of Cancer Using Recombinant Adenovirus Expressing Type III interferon IL-28A or IL-29 Peer-reviewed

Numasaki Muneo, Tagawa Masatoshi, Tsukamoto Hiroki, Tomioka Yoshihisa, Ohrui Takashi, Arai Hiroyuki

IMMUNOTHERAPY: OPEN ACCESS　2　(4)　1000131　2016
Leucine-rich repeat 2 of human Toll-like receptor 4 contains the binding site for inhibitory monoclonal antibodies Peer-reviewed

Hiroki Tsukamoto, Ippo Ukai, Yuki Yamagata, Shino Takeuchi, Kanae Kubota, Sao Kozakai, Naoto Suzuki, Masao Kimoto, Yoshihisa Tomioka

FEBS LETTERS　589　(24)　3893-3898　2015/12

DOI： 10.1016/j.febslet.2015.11.018 　

ISSN： 0014-5793

eISSN： 1873-3468
Immuno-Northern Blotting: Detection of RNA Modifications by Using Antibodies against Modified Nucleosides Peer-reviewed

Eikan Mishima, Daisuke Jinno, Yasutoshi Akiyama, Kunihiko Itoh, Shinnosuke Nankumo, Hisato Shima, Koichi Kikuchi, Yoichi Takeuchi, Alaa Elkordy, Takehiro Suzuki, Kuniyasu Niizuma, Sadayoshi Ito, Yoshihisa Tomioka, Takaaki Abe

PLOS ONE　10　(11)　2015/11

DOI： 10.1371/journal.pone.0143756 　

ISSN： 1932-6203
Dopamine or biopterin deficiency potentiates phosphorylation at (40)Ser and ubiquitination of tyrosine hydroxylase to be degraded by the ubiquitin proteasome system Peer-reviewed

Ichiro Kawahata, Shiori Ohtaku, Yoshihisa Tomioka, Hiroshi Ichinose, Tohru Yamakuni

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　465　(1)　53-58　2015/09

DOI： 10.1016/j.bbrc.2015.07.125 　

ISSN： 0006-291X

eISSN： 1090-2104
乳がんFEC100療法におけるホスアプレピタント注とアプレピタントカプセルの有効性と安全性の比較

渡邊桂子, 菊地正史, 木皿重樹, 小笠原喜美代, 久道周彦, 石田孝宣, 鈴木直人, 村井ユリ子, 島田美樹, 富岡佳久, 石岡千加史, 眞野成康

医薬品相互作用研究　39　(1)　29-35　2015/08
Publisher: 医薬品相互作用研究会
ISSN： 0385-5015
Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD Peer-reviewed

Eikan Mishima, Shinji Fukuda, Hisato Shinna, Akiyoshi Hirayama, Yasutoshi Akiyama, Yoichi Takeuchi, Noriko N. Fukuda, Takehiro Suzuki, Chitose Suzuki, Akinori Yuri, Koichi Kikuchi, Yoshihisa Tomioka, Sadayoshi Ito, Tomoyoshi Soga, Takaaki Abe

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　26　(8)　1787-1794　2015/08

DOI： 10.1681/ASN.2014060530 　

ISSN： 1046-6673

eISSN： 1533-3450
Mitochonic Acid 5 (MA-5), a Derivative of the Plant Hormone Indole-3-Acetic Acid, Improves Survival of Fibroblasts from Patients with Mitochondrial Diseases Peer-reviewed

Takehiro Suzuki, Hiroaki Yamaguchi, Motoi Kikusato, Tetsuro Matsuhashi, Akihiro Matsuo, Takeya Sato, Yuki Oba, Shun Watanabe, Daichi Minaki, Daisuke Saigusa, Hiroko Shimbo, Nobuyoshi Mori, Eikan Mishima, Hisato Shima, Yasutoshi Akiyama, Yoichi Takeuchi, Akinori Yuri, Koichi Kikuchi, Takafumi Toyohara, Chitose Suzuki, Masahiro Kohzuki, Jun-ichi Anzai, Nariyasu Mano, Shigeo Kure, Teruyuki Yanagisawa, Yoshihisa Tomioka, Masaaki Toyomizu, Sadayoshi Ito, Hitoshi Osaka, Ken-ichiro Hayashi, Takaaki Abe

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　236　(3)　225-232　2015/07

DOI： 10.1620/tjem.236.225 　

ISSN： 0040-8727

eISSN： 1349-3329
Outcomes of a Long-term Case Review Program during the On-site Training of Pharmacy Students Peer-reviewed

Yuriko Murai, Hiroyuki Suzuki, Masaru Mori, Hidehisa Tasaka, Naoto Suzuki, Miki Shimada, Hiroshi Sato, Noriyasu Hirasawa, Nariyasu Mano, Yoshihisa Tomioka

YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN　135　(7)　917-923　2015/07

ISSN： 0031-6903
新規ヒトTLR4モノクローナル抑制抗体のエピトープ解析

鵜飼一歩, 塚本宏樹, 山形由貴, 鈴木直人, 富岡佳久

日本薬学会年会要旨集　135年会　(3)　167-167　2015/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
CD14のLPS結合能とTLR4内在化の機能連関

武内偲乃, 塚本宏樹, 鵜飼一歩, 山形由貴, 久保田佳苗, 小坂井沙緒, 富岡佳久

日本薬学会年会要旨集　135年会　(3)　170-170　2015/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
Functional characterization of 10 CYP4A11 allelic variants to evaluate the effect of genotype on arachidonic acid omega-hydroxylation Peer-reviewed

Takahiro Saito, Masashi Honda, Masamitsu Takahashi, Chiharu Tsukada, Miyabi Ito, Yuki Katono, Hiroki Hosono, Daisuke Saigusa, Naoto Suzuki, Yoshihisa Tomioka, Noriyasu Hirasawa, Masahiro Hiratsuka

DRUG METABOLISM AND PHARMACOKINETICS　30　(1)　119-122　2015/02

DOI： 10.1016/j.dmpk.2014.09.001 　

ISSN： 1347-4367

eISSN： 1880-0920
Determination of sphingolipids by LC-MS/MS Peer-reviewed

Tomohiro Takahashi, Chihiro Takeda, Kohei Saito, Naoto Suzuki, Hiroki Tsukamoto, Yoshihisa Tomioka

Bioactive Lipid Mediators: Current Reviews and Protocols　357-370　2015/01/01
Publisher: Springer Japan
DOI： 10.1007/978-4-431-55669-5_26 　
神経変性疾患と受容体機能性Toll様受容体4抗体による敗血症治療と病態解析への応用

塚本宏樹, 富岡佳久

応用薬理　87　(1-2)　39-39　2014/10
Publisher: 応用薬理研究会
ISSN： 0300-8533
機能抑制型抗ヒトTLR4モノクローナル抗体は不活性型TLR4二量体構造を誘導する

山形由貴, 塚本宏樹, 鵜飼一歩, 鈴木直人, 富岡佳久

日本生化学会大会プログラム・講演要旨集　87回　[4P-452]　2014/10
Publisher: (公社)日本生化学会
Separation and quantification of 2-acyl-1-lysophospholipids and 1-acyl-2-lysophospholipids in biological samples by LC-MS/MS Peer-reviewed

Michiyo Okudaira, Asuka Inoue, Akira Shuto, Keita Nakanaga, Kuniyuki Kano, Kumiko Makide, Daisuke Saigusa, Yoshihisa Tomioka, Junken Aoki

JOURNAL OF LIPID RESEARCH　55　(10)　2178-2192　2014/10

DOI： 10.1194/jlr.D048439 　

ISSN： 0022-2275

eISSN： 1539-7262
Conformational Change in Transfer RNA Is an Early Indicator of Acute Cellular Damage Peer-reviewed

Eikan Mishima, Chisako Inoue, Daisuke Saigusa, Ryusuke Inoue, Koki Ito, Yusuke Suzuki, Daisuke Jinno, Yuri Tsukui, Yosuke Akamatsu, Masatake Araki, Kimi Araki, Ritsuko Shimizu, Haruka Shinke, Takehiro Suzuki, Yoichi Takeuchi, Hisato Shima, Yasutoshi Akiyama, Takafumi Toyohara, Chitose Suzuki, Yoshikatu Saiki, Teiji Tominaga, Shigehito Miyagi, Naoki Kawagisihi, Tomoyoshi Soga, Takayoshi Ohkubo, Kenichi Yamamura, Yutaka Imai, Satohiro Masuda, Venkata Sabbisetti, Takaharu Ichimura, David B. Mount, Joseph V. Bonventre, Sadayoshi Ito, Yoshihisa Tomioka, Kunihiko Itoh, Takaaki Abe

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　25　(10)　2316-2326　2014/10

DOI： 10.1681/ASN.2013091001 　

ISSN： 1046-6673

eISSN： 1533-3450
Overexpression of autotaxin, a lysophosphatidic acid-producing enzyme, enhances cardia bifida induced by hypo-sphingosine-1-phosphate signaling in zebrafish embryo Peer-reviewed

Keita Nakanaga, Kotaro Hama, Kuniyuki Kano, Takanao Sato, Hiroshi Yukiura, Asuka Inoue, Daisuke Saigusa, Hidetoshi Tokuyama, Yoshihisa Tomioka, Hiroshi Nishina, Atsuo Kawahara, Junken Aoki

JOURNAL OF BIOCHEMISTRY　155　(4)　235-241　2014/04

DOI： 10.1093/jb/mvt114 　

ISSN： 0021-924X

eISSN： 1756-2651
抗1-methyladenosine抗体反応性分子の同定を目的としたtRNA分子種の解析法に関する研究

津久井佑梨, 陣野大輔, 三島英換, 鈴木直人, 塚本宏樹, 三枝大輔, 伊藤邦彦, 阿部高明, 富岡佳久

日本薬学会年会要旨集　134年会　(2)　275-275　2014/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
リコカルコンAのCOX-1活性抑制メカニズムの解明

菅原大貴, 田代匠, 三枝大輔, 塚本宏樹, 奥田亜沙, 小原祐太郎, 鈴木直人, 富岡佳久

日本薬学会年会要旨集　134年会　(4)　58-58　2014/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
A validated quantitative liquid chromatography-tandem quadrupole mass spectrometry method for monitoring isotopologues to evaluate global modified cytosine ratios in genomic DNA Peer-reviewed

Makoto Tsuji, Hironori Matsunaga, Daisuke Jinno, Hiroki Tsukamoto, Naoto Suzuki, Yoshihisa Tomioka

JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES　953　38-47　2014/03

DOI： 10.1016/j.jchromb.2014.01.050 　

ISSN： 1570-0232

eISSN： 1873-376X
Novel actin-based regulatory mechanism of nigrostriatal dopaminergic function by V-1 in vitro and in vivo Peer-reviewed

Ichiro Kawahata, Lai Yanxin, Shiori Ohtaku, Junichi Morita, Shigeki Kato, Akiko Tabuchi, Mamoru Fukuchi, Masaaki Tsuda, Kazumasa Ohashi, Kensaku Mizuno, Yasuhiko Izumi, Toshiaki Kume, Akinori Akaike, Yoshihisa Tomioka, Chiho Sumi-Ichinose, Kazunao Kondo, Hiroshi Ichinose, Kazuto Kobayashi, Tohru Yamakuni

JOURNAL OF PHARMACOLOGICAL SCIENCES　124　79P-79P　2014

ISSN： 1347-8613

eISSN： 1347-8648
Potent activity of nobiletin-rich Citrus reticulata peel extract to facilitate cAMP/PKA/ERK/CREB signaling associated with learning and memory in cultured hippocampal neurons: identification of the substances responsible for the pharmacological action Peer-reviewed

Ichiro Kawahata, Masaaki Yoshida, Wen Sun, Akira Nakajima, Yanxin Lai, Naoya Osaka, Kentaro Matsuzaki, Akihito Yokosuka, Yoshihiro Mimaki, Akira Naganuma, Yoshihisa Tomioka, Tohru Yamakuni

JOURNAL OF NEURAL TRANSMISSION　120　(10)　1397-1409　2013/10

DOI： 10.1007/s00702-013-1025-x 　

ISSN： 0300-9564

eISSN： 1435-1463
MD-2-dependent human Toll-like receptor 4 monoclonal antibodies detect extracellular association of Toll-like receptor 4 with extrinsic soluble MD-2 on the cell surface Peer-reviewed

Hiroki Tsukamoto, Hideyuki Ihara, Ritsu Ito, Ippo Ukai, Naoto Suzuki, Masao Kimoto, Yoshihisa Tomioka, Yoshitaka Ikeda

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　440　(1)　31-36　2013/10

DOI： 10.1016/j.bbrc.2013.09.004 　

ISSN： 0006-291X

eISSN： 1090-2104
SLC10A4 is a protease-activated transporter that transports bile acids Peer-reviewed

Takuya Abe, Yoshitomi Kanemitu, Masateru Nakasone, Ichiro Kawahata, Tohru Yamakuni, Akira Nakajima, Naoto Suzuki, Masazumi Nishikawa, Takanori Hishinuma, Yoshihisa Tomioka

JOURNAL OF BIOCHEMISTRY　154　(1)　93-101　2013/07

DOI： 10.1093/jb/mvt031 　

ISSN： 0021-924X

eISSN： 1756-2651
Indoxyl Sulfate Down-Regulates SLCO4C1 Transporter through Up-Regulation of GATA3 Peer-reviewed

Yasutoshi Akiyama, Koichi Kikuchi, Daisuke Saigusa, Takehiro Suzuki, Yoichi Takeuchi, Eikan Mishima, Yasuaki Yamamoto, Ayako Ishida, Daiki Sugawara, Daisuke Jinno, Hisato Shima, Takafumi Toyohara, Chitose Suzuki, Tomokazu Souma, Takashi Moriguchi, Yoshihisa Tomioka, Sadayoshi Ito, Takaaki Abe

PLOS ONE　8　(7)　2013/07

DOI： 10.1371/journal.pone.0066518 　

ISSN： 1932-6203
【最新生理活性脂質研究-実験手法、基礎的知識とその応用-】(第1章)技術編スフィンゴ脂質の質量分析法

富岡佳久, 鈴木直人, 三枝大輔

遺伝子医学MOOK　(24)　55-62　2013/05
Publisher: (株)メディカルドゥ
ISSN： 1349-2527
エリスロポエチン産生を増強させる化合物群の探索と同定(その2)

鈴木雄介, 佐原利人, 池之内初, 小原万天, 鈴木健弘, 鈴木千登勢, 三島英換, 竹内陽一, 三枝大輔, 富岡佳久, 伊藤貞嘉, 林謙一郎, 阿部高明

日本腎臓学会誌　55　(3)　345-345　2013/04
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
ラニチジン注とファモチジン注のパクリタキセル注前投与におけるアレルギー発現率の比較

片岡佑太, 菊地正史, 中川直人, 木皿重樹, 高橋哉子, 小笠原喜美代, 我妻恭行, 久道周彦, 小原拓, 鈴木直人, 村井ユリ子, 島田美樹, 富岡佳久, 石岡千加史, 眞野成康

日本薬学会年会要旨集　133年会　(4)　184-184　2013/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
次世代型専門薬剤師育成を目指した大学院教育システムの開発

鈴木直人, 大内麻由, 黒澤真帆, 金光祥臣, 松本周平, 三村享, 三枝大輔, 木皿重樹, 村井ユリ子, 眞野成康, 富岡佳久

日本薬学会年会要旨集　133年会　(4)　242-242　2013/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
東北大学における6年制薬剤師教育

村井ユリ子, 富岡佳久

医薬品相互作用研究　36　39-43　2013
Repeated treatment with nicotine induces phosphorylation of NMDA receptor NR2B subunit in the brain regions involved in behavioral sensitization Peer-reviewed

Akira Nakajima, Yukari Kinugasa, Jun Torii, Takanori Hishinuma, Yoshihisa Tomioka, Kiyofumi Yamada, Tohru Yamakuni

NEUROSCIENCE LETTERS　524　(2)　133-138　2012/08

DOI： 10.1016/j.neulet.2012.07.022 　

ISSN： 0304-3940

eISSN： 1872-7972
A Distinct Regulatory Role of Th17 Cytokines IL-17A and IL-17F in Chemokine Secretion from Lung Microvascular Endothelial Cells Peer-reviewed

Hitomi Fujie, Kaijun Niu, Michiru Ohba, Yoshihisa Tomioka, Haruki Kitazawa, Kengo Nagashima, Takashi Ohrui, Muneo Numasaki

INFLAMMATION　35　(3)　1119-1131　2012/06

DOI： 10.1007/s10753-011-9419-0 　

ISSN： 0360-3997
Simultaneous quantitation of sphingoid bases and their phosphates in biological samples by liquid chromatography/electrospray ionization tandem mass spectrometry Peer-reviewed

Daisuke Saigusa, Kanako Shiba, Asuka Inoue, Kotaro Hama, Michiyo Okutani, Nagisa Iida, Masayoshi Saito, Kaori Suzuki, Tohru Kaneko, Naoto Suzuki, Hiroaki Yamaguchi, Nariyasu Mano, Junichi Goto, Takanori Hishinuma, Junken Aoki, Yoshihisa Tomioka

ANALYTICAL AND BIOANALYTICAL CHEMISTRY　403　(7)　1897-1905　2012/06

DOI： 10.1007/s00216-012-6004-9 　

ISSN： 1618-2642
LC/MS/MSを用いたアルギニン代謝関連物質定量分析系の構築

三枝大輔, 石田綾子, 菅原大貴, 鈴木直人, 阿部高明, 富岡佳久

日本腎臓学会誌　54　(3)　302-302　2012/04
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
オキサリプラチン誘発性末梢神経障害の発生因子と発生予測式の臨床薬剤学的応用性の検証

田中敏, 三村亨, 黒澤真帆, 村井ユリ子, 三枝大輔, 鈴木直人, 蒲生真紀夫, 佐藤益男, 富岡佳久

日本薬学会年会要旨集　132年会　(4)　201-201　2012/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
Development of Advanced Educational Programs Including Research Programs for Undergraduate Students in National Universities: The Facts in 2010 Peer-reviewed

Yuji Kurosaki, Yoshihisa Tomioka, Tomofumi Santa, Yoshihisa Kitamura

YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN　132　(3)　351-356　2012/03

DOI： 10.1248/yakushi.132.351 　

ISSN： 0031-6903
Serum Chlorine Level as a Possible Predictive Factor for Oxaliplatin-Induced Peripheral Neuropathy

Satoshi Tanaka, Naoto Suzuki, Akira Mimura, Kaho Kurosawa, Yuriko Murai, Daisuke Saigusa, Makio Gamoh, Masuo Sato, Yoshihisa Tomioka

Pharmacology & Pharmacy　03　(01)　44-51　2012
Publisher: Scientific Research Publishing, Inc.
DOI： 10.4236/pp.2012.31007 　

ISSN： 2157-9423

eISSN： 2157-9431
Evaluation of Pre-hospital Clinical Training in Advanced Pharmacy Education in Japan

Hashimoto Takanao, Ohkubo Takayoshi, Takahashi Nobuyuki, Murai Yuriko, Sato Keiko, Terata Shiho, Metoki Hirohito, Kikuya Masahiro, Hirasawa Noriyasu, Tomioka Yoshihisa, Oba Masatoshi, Imai Yutaka, Sato Hiroshi

Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences)　38　(5)　322-331　2012
Publisher: Japanese Society of Pharmaceutical Health Care and Sciences
DOI： 10.5649/jjphcs.38.322 　

ISSN： 1346-342X

More details Close

During the 6-year pharmacy program, students receive clinically oriented pharmacy education that develops their expertise in effectively and safely managing patients drug use. In our university, pre-hospital clinical training (PHCT) has been conducted during the 4th year in order to prepare students for practical clinical training in hospital and community pharmacies in the 5th year. In addition to the core curriculum, the following six categories of advanced training are performed during PHCT: (1) basic life support based on the American Heart Association guidelines for cardiopulmonary resuscitation; (2) evaluation of vital signs using an emergency care simulator; (3) evaluation of drug adverse effects (acute and chronic); (4) clinical case analysis and presentation; (5) blood pressure measurement using auscultation and neurological examinations; and (6) simulation as a clinical research coordinator receiving informed consent. Students (N=22) were administered questionnaires regarding their evaluations of PHCT and their hopes for the future. The results of the questionnaire on PHCT revealed positive evaluations for the practical usefulness of the advanced training categories (1), (3) and (5). However, the other advanced training categories were not evaluated highly because students found them difficult to understand within a limited period. Analysis of the students future hopes revealed that approximately half of the students would like to work in hospitals as a pharmacy specialist. Furthermore, they want to study basic skills during the 5th year. In conclusion, administering questionnaires on students opinions and their study needs was useful for objectively evaluating our program.
Anti-dementia action of the extracts from Citrus tachibana peels and N chinpi, new beneficial natural resources Peer-reviewed

Wen Sun, Ichiro Kawahata, Masaaki Yoshida, Daisuke Saigusa, Akihito Yokosuka, Yutaka Sashida, Yoshihiro Mimaki, Katsuya Saito, Yoshihisa Tomioka, Tohru Yamakuni

JOURNAL OF PHARMACOLOGICAL SCIENCES　118　188P-188P　2012

ISSN： 1347-8613
Functional Characterization of CYP2B6 Allelic Variants in Demethylation of Antimalarial Artemether Peer-reviewed

Masashi Honda, Yuka Muroi, Yuichiro Tamaki, Daisuke Saigusa, Naoto Suzuki, Yoshihisa Tomioka, Yoichi Matsubara, Akifumi Oda, Noriyasu Hirasawa, Masahiro Hiratsuka

DRUG METABOLISM AND DISPOSITION　39　(10)　1860-1865　2011/10

DOI： 10.1124/dmd.111.040352 　

ISSN： 0090-9556
High-performance liquid chromatography with photodiode array detection for determination of nobiletin content in the brain and serum of mice administrated the natural compound Peer-reviewed

Daisuke Saigusa, Masatoshi Shibuya, Daisuke Jinno, Hiroyuki Yamakoshi, Yoshiharu Iwabuchi, Akihito Yokosuka, Yoshihiro Mimaki, Akira Naganuma, Yasushi Ohizumi, Yoshihisa Tomioka, Tohru Yamakuni

ANALYTICAL AND BIOANALYTICAL CHEMISTRY　400　(10)　3635-3641　2011/07

DOI： 10.1007/s00216-011-5031-2 　

ISSN： 1618-2642

eISSN： 1618-2650
Education for Six-years Graduate School of Pharmaceutical Sciences: A Case of Tohoku University Peer-reviewed

Yoshihisa Tomioka, Noriyasu Hirasawa, Akira Naganuma

YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN　131　(6)　933-938　2011/06

DOI： 10.1248/yakushi.131.933 　

ISSN： 0031-6903
HPLC/PDA法を用いた体内動態解析による抗アルツハイマー病天然薬物ノビレチンの脳内移行の証明

三枝大輔, 中島晶, 鐵尚美, 澁谷正俊, 山越博幸, 岩渕好治, 横須賀章人, 指田豊, 三巻祥浩, 永沼章, 大泉康, 富岡佳久

日本薬学会年会要旨集　131年会　(4)　139-139　2011/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
ヒト小脳由来TE671細胞におけるプロテアーゼ活性化トランスポーターの機能解析

阿部拓哉, 中島晶, 金光祥臣, 三枝大輔, 鈴木直人, 富岡佳久, 菱沼隆則

日本薬学会年会要旨集　131年会　(4)　213-213　2011/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
LC/MS/MSを用いたOATP1B3の絶対定量と過剰発現細胞のプロテオーム解析

金光祥臣, 阿部拓哉, 中曽根正皓, 三枝大輔, 菱沼隆則, 鈴木直人, 富岡佳久

日本薬学会年会要旨集　131年会　(4)　213-213　2011/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
地域薬局における慢性腎臓病に対する食での取り組み

崎野健一, 尾崎敦子, 尾形みなみ, 小林満, 岩倉大介, 星友典, 金光祥臣, 山岸祐輔, 三枝大輔, 山家靖, 鈴木直人, 大野武, 富岡佳久

日本薬学会年会要旨集　131年会　(4)　276-276　2011/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
生体内transアコニット酸生成機構解明のための有機酸高感度定量法の確立

松本周平, 三枝大輔, 竹田千尋, 鈴木直人, 澁谷正俊, 岩渕好治, 富岡佳久

日本薬学会年会要旨集　131年会　(4)　288-288　2011/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
オキサリプラチン誘発性末梢神経障害の発現頻度・重篤度予測因子の探索

三村享, 田中敏, 三枝大輔, 鈴木直人, 村井ユリ子, 蒲生真紀夫, 佐藤益男, 富岡佳久

日本薬学会年会要旨集　131年会　(4)　301-301　2011/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
オキサリプラチン誘発性末梢神経障害と生体中グアニジノコハク酸濃度変化による影響

三枝大輔, 石田綾子, 高橋舞, 芝可奈子, 菅原大貴, 津久井佑梨, 山岸佑輔, 三村享, 鈴木直人, 富岡佳久

日本薬学会年会要旨集　131年会　(4)　326-326　2011/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
Determination of Asymmetric Dimethylarginine and Symmetric Dimethylarginine in Biological Samples of Mice Using LC/MS/MS

Daisuke Saigusa, Mai Takahashi, Yoshitomi Kanemitsu, Ayako Ishida, Takaaki Abe, Tohru Yamakuni, Naoto Suzuki, Yoshihisa Tomioka

American Journal of Analytical Chemistry　02　(03)　303-313　2011
Publisher: Scientific Research Publishing, Inc.
DOI： 10.4236/ajac.2011.23038 　

ISSN： 2156-8251

eISSN： 2156-8278
Impact of the Oral Adsorbent AST-120 on Organ-Specific Accumulation of Uremic Toxins: LC-MS/MS and MS Imaging Techniques Peer-reviewed

Sato E, Saigusa D, Mishima E, Uchida T, Miura D, Morikawa-Ichinose T, Kisu K, Sekimoto A, Saito R, Oe Y, Matsumoto Y, Tomioka Y, Mori T, Takahashi N, Sato H, Abe T, Niwa T, Ito S

Toxins (Basel)　10　(1)　pii: E19　2011
Simultaneous determination of guanidinosuccinic acid and guanidinoacetic acid in urine using high performance liquid chromatography/tandem mass spectrometry Peer-reviewed

Daisuke Saigusa, Naoto Suzuki, Mai Takahashi, Kanako Shiba, Satoshi Tanaka, Takaaki Abe, Takanori Hishinuma, Yoshihisa Tomioka

ANALYTICA CHIMICA ACTA　677　(2)　169-175　2010/09

DOI： 10.1016/j.aca.2010.08.005 　

ISSN： 0003-2670
ローマ野菜プンタレッラ含有セスキテルペン類のプロスタグランジン代謝に及ぼす影響 Peer-reviewed

西川正純, 阿部拓哉, 鈴木香織, 菰田俊一, 山國徹, 富岡佳久, 菱沼隆則

応用薬理　78　(5-6)　160-160　2010/08
Publisher: 応用薬理研究会
ISSN： 0300-8533
大学院生の薬剤師研修を通じた医師への処方支援 Peer-reviewed

三村享, 松本周平, 金光祥臣, 村井ユリ子, 久道周彦, 佐藤真由美, 鈴木直人, 齊藤直美, 土屋雅美, 木皿重樹, 三枝大輔, 眞野成康, 富岡佳久

日本薬学会年会要旨集　130年会　(4)　348-348　2010/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
P2-559 プログラム選択方式により学生の自主性を重視した病院実習プログラムの構築(一般演題ポスター発表,薬学教育(実務実習),臨床から学び臨床へと還元する医療薬学)

村井ユリ子, 平塚真弘, 平澤典保, 富岡佳久, 島田美樹, 眞野成康, 佐賀利英, 佐藤真由美, 中村浩規, 久道周彦, 我妻恭行, 鈴木裕之, 森大, 鈴木直人

日本医療薬学会年会講演要旨集　20　483-483　2010
Publisher: 一般社団法人日本医療薬学会
DOI： 10.20825/amjsphcs.20.0_483_1 　
Neurobehavioral effects of tetrabromobisphenol A, a brominated flame retardant, in mice Peer-reviewed

Akira Nakajima, Daisuke Saigusa, Naomi Tetsu, Tohru Yamakuni, Yoshihisa Tomioka, Takanori Hishinuma

TOXICOLOGY LETTERS　189　(1)　78-83　2009/08

DOI： 10.1016/j.toxlet.2009.05.003 　

ISSN： 0378-4274

eISSN： 1879-3169
4 '-Demethylnobiletin, a Bioactive Metabolite of Nobiletin Enhancing PKA/ERK/CREB Signaling, Rescues Learning Impairment Associated with NMDA Receptor Antagonism via Stimulation of the ERK Cascade Peer-reviewed

Md Al Rahim, Akira Nakajima, Daisuke Saigusa, Naomi Tetsu, Yuji Maruyama, Masatoshi Shibuya, Hiroyuki Yamakoshi, Yoshihisa Tomioka, Yoshiharu Iwabuchi, Yasushi Ohizumi, Tohru Yamakuni

BIOCHEMISTRY　48　(32)　7713-7721　2009/08

DOI： 10.1021/bi901088w 　

ISSN： 0006-2960
宮城県産ローマ野菜プンタレッラ中のセスキテルペン類のプロスタグランジンD2産生に及ぼす影響 Peer-reviewed

阿部拓哉, 鈴木香織, 菰田俊一, 山國徹, 富岡佳久, 菱沼隆則, 西川正純

日本薬学会年会要旨集　129年会　(3)　113-113　2009/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
Simultaneous quantification of seven prostanoids using liquid chromatography/tandem mass spectrometry: The effects of arachidonic acid on prostanoid production in mouse bone marrow-derived mast cells Peer-reviewed

Takanori Hishinuma, Kaori Suzukia, Masayoshi Saitoa, Hiroaki Yamaguchi, Naoto Suzuki, Yoshihisa Tomioka, Izumi Kaneko, Masao Ono, Junichi Goto

PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS　76　(6)　321-329　2007/06

DOI： 10.1016/j.plefa.2007.04.005 　

ISSN： 0952-3278
Genetic variation in ABCB1 influences paclitaxel pharmacokinetics in Japanese patients with ovarian cancer Peer-reviewed

Yamaguchi H, Hishinuma T, Endo N, Tsukamoto H, Kishikawa Y, Sato M, Murai Y, Hiratsuka M, Ito K, Okamura C, Yaegashi N, Suzuki N, Tomioka Y, Goto J

Int J Gynecol Cancer　16　(3)　979-985　2006/05
Publisher: BMJ
DOI： 10.1111/j.1525-1438.2006.00593.x 　

ISSN： 1048-891X

eISSN： 1525-1438
LC/ESI-MS/MSを用いた免疫抑制剤シロリムスの血中濃度測定

鈴木直人, 菱沼隆則, 山口浩明, 佐藤真由美, 金子達, 松浦正樹, 上西智子, 中村浩規, 小澤実香, 富岡佳久, 和田基, 石井智浩, 林富, 後藤順一

医療薬学　32　(4)　289-294　2006/04
Publisher: (一社)日本医療薬学会
DOI： 10.5649/jjphcs.32.289 　

ISSN： 1346-342X
The induction of prostaglandin E synthase and upregulation of cyclooxygenase-2 by 9-cis retinoic acid. International-journal Peer-reviewed

Tsukamoto H, Hishinuma T, Tayama R, Narahara K, Suzuki N, Tomioka Y, Goto J

Prostaglandins & other lipid mediators　74　(1-4)　61-74　2004/10

DOI： 10.1016/j.prostaglandins.2004.07.001 　

ISSN： 1098-8823

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9-cis Retinoic acid (9cRA) is a promising lead compound to design the retinoid X receptor (RXR) ligands with the ability to simultaneously activate RXR heterodimers with the selectivity to their nuclear receptor partners. In this study, we investigated the effects of 9cRA on the prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) production. 9cRA increased the PGE2 and TXA2 productions in the presence of lipopolysaccharide (LPS). All-trans retinoic acid, the retinoic acid receptor ligand, also increased their production. We revealed that cyclooxygenase (COX)-2 was clearly induced by 9cRA in the presence of LPS. The induction was not suppressed by indomethacin, which completely inhibited the increase in the LPS-stimulated prostanoid production by 9cRA. The expression levels of the toll-like receptor 4 and CD14, which were components of the LPS receptor complex, were increased by 9cRA in the presence and absence of LPS. PGE synthase was also clearly increased by 9cRA in the presence and absence of LPS. In this study, we noted that 9cRA increased the production of PGE2 and TXA2 by the induction of COX-2 and PGE synthase in the presence of LPS. The induction of the LPS receptor complex by 9cRA is able to upregulate the induction of COX-2 by LPS.
IL-17 and IL-17F modulate GM-CSF production by lung microvascular endothelial cells stimulated with IL-1β and/or TNF-α Peer-reviewed

Muneo Numasaki, Yoshihisa Tomioka, Hidenori Takahashi, Hidetada Sasaki

Immunology Letters　95　(2)　175-184　2004/09

DOI： 10.1016/j.imlet.2004.07.002 　

ISSN： 0165-2478
Elevated expression level of 60-kDa subunit of tRNA-guanine transglycosylase in colon cancer Peer-reviewed

Shunji Ishiwata, Yasuko Ozawa, Jun Katayama, Shuko Kaneko, Hiroki Shindo, Yoshihisa Tomioka, Toshiyuki Ishiwata, Goro Asano, Shigeo Ikegawa, Michinao Mizugaki

Cancer Letters　212　(1)　113-119　2004/08/20

DOI： 10.1016/j.canlet.2004.03.009 　

ISSN： 0304-3835
Regulatory roles of IL-17 and IL-17F in G-CSF production by lung microvascular endothelial cells stimulated with IL-1β and/or TNF-α Peer-reviewed

Muneo Numasaki, Hidenori Takahashi, Yoshihisa Tomioka, Hidetada Sasaki

Immunology Letters　95　(1)　97-104　2004/08/15

DOI： 10.1016/j.imlet.2004.06.010 　

ISSN： 0165-2478
Phage-display selection of antibodies to the left end of CTX3C using synthetic fragments Peer-reviewed

Yoko Nagumo, Hiroki Oguri, Kouhei Tsumoto, Yumi Shindo, Masahiro Hirama, Takeshi Tsumuraya, Ikuo Fujii, Yoshihisa Tomioka, Michinao Mizugaki, Izumi Kumagai

Journal of Immunological Methods　289　(1-2)　137-146　2004/06

DOI： 10.1016/j.jim.2004.04.003 　

ISSN： 0022-1759
Thiazolidinediones increase arachidonic acid release and subsequent prostanoid production in a peroxisome proliferator-activated receptor gamma-independent manner. International-journal Peer-reviewed

Tsukamoto H, Hishinuma T, Suzuki N, Tayama R, Hiratsuka M, Yoshihisa T, Mizugaki M, Goto J

Prostaglandins & other lipid mediators　73　(3-4)　191-213　2004/04

DOI： 10.1016/j.prostaglandins.2004.01.008 　

ISSN： 1098-8823

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Thiazolidinedione, peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, has been used as an anti-diabetic drug and as an useful tool to elucidate multiple PPARgamma functions by in vitro and in vivo studies. We investigated the effects of thiazolidinediones on prostanoid production in lipopolysaccharide-stimulated cells. The high concentrations (>10 microM) of rosiglitazone and pioglitazone significantly increased lipopolysaccharide-stimulated prostanoid production such as thromboxane A2 and prostaglandin E2. However, PPARgamma antagonist could not inhibit them. In PPARgamma-deficient cells, thiazolidinediones increased prostaglandin E2 production. Thiazolidinediones increased arachidonic acid (AA) release from the cell membrane by not stimulating AA releasing process involving several phospholipase A2s but inhibiting AA reuptaking process. The expression of cyclooxygenase-1 and cyclooxygenase-2 were not affected by thiazolidinediones. In this study, we demonstrated that high concentrations of TZDs increased AA release by the inhibition of AA reuptaking process, leading to subsequent increase in the prostanoid production in a PPARgamma-independent manner. This mechanism provides useful information for the elucidation of multiple PPARgamma functions and diabetic drug therapy.
Swine Toll-like receptor9 recognizes CpG motifs of human cell stimulant Peer-reviewed

Shimosato, T, Kitazawa, H, Katoh, S, Tomioka, Y, Karima, R, Ueha, S, Kawai, Y, Hishinuma, T, Matsushima, K, Saito, T

Biochim. Biophys. Acta　1627　56-61　2003/08

DOI： 10.1016/S0167-4781(03)00048-4 　

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IF=2.137 BIOCHEMISTRY & MOLECULAR BIOLOGY分野で114位／261
Characterization of 11-dehydro-thromboxane B-2 recombinant antibody obtained by phage display technology Peer-reviewed

LR Tsuruta, Y Tomioka, T Hishinuma, Y Kato, K Itoh, T Suzuki, H Oguri, M Hirama, J Goto, M Mizugaki

PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS　68　(4)　273-284　2003/04

DOI： 10.1016/S0952-3278(03)00006-1 　

ISSN： 0952-3278
抗グリチルレチン酸モノクローナル抗体の反応性に寄与する軽鎖構造の解析

佐々木美冴, 富岡佳久, 加藤芳徳, Tsuruta Lilian R., 工藤義樹, 伊藤邦彦, 鈴木敏夫, 菱沼隆則, 平間正博, 後藤順一, 水柿道直

日本薬学会年会要旨集　123年会　(4)　160-160　2003/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
Simultaneous quantification of prostaglandins in human synovial cell-cultured medium using liquid chromatography/tandem mass spectrometry Peer-reviewed

Takabatake M, Hishinuma T, Suzuki N, Chiba S, Tsukamoto H, Nakamura H, Saga T, Tomioka Y, Kurose A, Sawai T, Mizugaki M

Prostaglandins Leukot Essent Fatty Acids　67　(1)　51-56　2002/07

DOI： 10.1054/plef.2002.0381 　
Simultaneous quantification of prostaglandins, isoprostane and thromboxane in cell-cultured medium using gas chromatography-mass spectrometry. Peer-reviewed

Tsukamoto H, Hishinuma T, Mikkaichi T, Nakamura H, Yamazaki T, Tomioka Y, Mizugaki M

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences　774　(2)　205-214　2002/07

DOI： 10.1016/S1570-0232(02)00220-9 　

ISSN： 1570-0232
Design, production, and characterization of recombinant neocarzinostatin apoprotein in Escherichia coli Peer-reviewed

S Nozaki, Y Tomioka, T Hishinuma, M Inoue, Y Nagumo, L Tsuruta, K Hayashi, T Matsumoto, Y Kato, S Ishiwata, K Itoh, T Suzuki, M Hirama, M Mizugaki

JOURNAL OF BIOCHEMISTRY　131　(5)　729-738　2002/05

ISSN： 0021-924X
Altered water barrier function in epidermal-type fatty acid binding protein-deficient mice Peer-reviewed

Y Owada, H Takano, H Yamanaka, H Kobayashi, Y Sugitani, Y Tomioka, Suzuki, I, R Suzuki, T Terui, M Mizugaki, H Tagami, T Noda, H Kondo

JOURNAL OF INVESTIGATIVE DERMATOLOGY　118　(3)　430-435　2002/03

DOI： 10.1046/j.0022-202x.2001.01616.x 　

ISSN： 0022-202X
A simultaneous LightCycler detection assay for five genetic polymorphisms influencing drug sensitivity Peer-reviewed

M Hiratsuka, K Narahara, Y Kishikawa, SI Hamdy, N Endo, Y Agatsuma, M Matsuura, T Inoue, Y Tomioka, M Mizugaki

CLINICAL BIOCHEMISTRY　35　(1)　35-40　2002/02

DOI： 10.1016/S0009-9120(02)00269-2 　

ISSN： 0009-9120
Analysis of Drug Interaction on Diazepam Binding Site of Human Serum Albumin : Screening of Drugs Binding to Diazepam Binding Site by ELISA for Glycyrrhetic Acid

Hayasaka Masataka, Tomioka Yoshihisa, Ishiwata Shunji, Mizugaki Michinao

Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences)　28　(2)　101-107　2002
Publisher: Japanese Society of Pharmaceutical Health Care and Sciences
DOI： 10.5649/jjphcs.28.101 　

ISSN： 1346-342X

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In order to clarify the binding site of drugs on human serum albumin (HSA), competition studies were carned out using ELISA for glycyrrhetic acid (GA), which is mainly bound to the diazepam site on HSA. The release of GA from HSA was detected as a displacement by the various drugs [bezafibrate (B), delapril HCI, diclofenac Na (D), doxifluridine, famotidine, ibuprofen (I), loxoprofen Na (L- 1) and its metabolite (loxoprofen Na trans-OH (L- 2 )), pravastatin Na]. The percentages of GA release by the addition of I, D, L- 1 , 2, which belong to nonsteroidal anti-inflammatory drugs, and B were 96.0%, 86.5%, 25.4%, 25.6% and 12.6% respectively. In addition, the percentages of GA release by addition of the other 4 drugs ranged between 3.2 and 4.1%. These results showed that I and D were strongly bound to the diazepam site, while the binding of L- 1 , L- 2 and B was weak. Thus, L- 1 , L- 2 and B may predominantly bind to other site (s) on HSA. Therefore, ELISA for GA was suggested to be helpful for studying the binding site (diazepam binding site) of the drugs on HSA.
Concise synthesis of ciguatoxin ABC-ring fragments and surface plasmon resonance study of the interaction of their BSA conjugates with monoclonal antibodies Peer-reviewed

Y Nagumo, H Oguri, Y Shindo, S Sasaki, T Oishi, M Hirama, Y Tomioka, M Mizugaki, T Tsumuraya

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS　11　(15)　2037-2040　2001/08

DOI： 10.1016/S0960-894X(01)00358-4 　

ISSN： 0960-894X
Influence of anesthesia on brain distribution of [C-11]methamphetamine in monkeys in positron emission tomography (PET) study Peer-reviewed

M Mizugaki, N Nakagawa, H Nakamura, T Hishinuma, Y Tomioka, S Ishiwata, T Ido, R Iwata, Y Funaki, M Itoh, M Higuchi, N Okamura, T Fujiwara, M Sato, K Shindo, S Yoshida

BRAIN RESEARCH　911　(2)　173-175　2001/08

DOI： 10.1016/S0006-8993(01)02669-5 　

ISSN： 0006-8993
Detection of angiotensin-converting enzyme insertion/deletion polymorphisms using real-time polymerase chain reaction and melting curve analysis with SYBR Green I on a GeneAmp 5700 Peer-reviewed

M Hiratsuka, Y Kishikawa, K Narahara, T Inoue, SI Hamdy, Y Agatsuma, Y Tomioka, M Mizugaki

ANALYTICAL BIOCHEMISTRY　289　(2)　300-303　2001/02

DOI： 10.1006/abio.2000.4945 　

ISSN： 0003-2697
cDNA cloning and expression of swine IL-7 from neonatal intestinal epithelium Peer-reviewed

S Ueha, H Kitazawa, Y Tomioka, Y Kawai, T Saito, T Itoh

BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION　1517　(3)　468-471　2001/02

DOI： 10.1016/S0167-4781(00)00304-3 　

ISSN： 0167-4781
Determination of serum concentrations of glycyrrhizin in humans by semi-micro high-performance liquid chromatography after administration of a therapeutic dose Peer-reviewed

S Ishiwata, K Nakashita, M Niizeki, N Suzuki, S Kaneko, Y Tomioka, T Hishinuma, M Mizugaki

BIOLOGICAL & PHARMACEUTICAL BULLETIN　23　(8)　904-905　2000/08

DOI： 10.1248/bpb.23.904 　

ISSN： 0918-6158
Fas-mediated apoptosis is enhanced by glycyrrhizin without alteration of caspase-3-like activity Peer-reviewed

S Ishiwata, K Nakashita, Y Ozawa, M Niizeki, S Nozaki, Y Tomioka, M Mizugaki

BIOLOGICAL & PHARMACEUTICAL BULLETIN　22　(11)　1163-1166　1999/11

DOI： 10.1248/bpb.22.1163 　

ISSN： 0918-6158
Effect of αl-acidic glycoprotein in the ascitic fluid of cancer patients on human NK cells : Selective suppression of interteron-induced NK activation Peer-reviewed

TOMIOKA Yoshihisa

Inflammation　23　(2)　117　1999
A 63 kDa tumor necrosis factor inhibitor released from a human monocytic leukemia cell line, THP-1 Peer-reviewed

H Aso, O Yoshie, Y Tomioka, MT Rose, M Mizugaki

MICROBIOLOGY AND IMMUNOLOGY　43　(1)　53-59　1999

DOI： 10.1111/j.1348-0421.1999.tb02372.x 　

ISSN： 0385-5600
Designed hapten aimed at anti-ciguatoxin monoclonal antibody: Synthesis, immunization and discrimination of the C2 configuration Peer-reviewed

H Oguri, S Tanaka, S Hishiyama, T Oishi, M Hirama, T Tumuraya, Y Tomioka, M Mizugaki

SYNTHESIS-STUTTGART　SI　1431-1436　1999

DOI： 10.1055/s-1999-3646 　

ISSN： 0039-7881
4 Pro-R hydrogen of NADPH was abstracted for enzymatic hydride transfer by N-ethylmaleimide reductase of Yarrowia lipolytica Peer-reviewed

M Mizugaki, K Miura, H Yamamoto, M KayabaNakazawa, K Edo, Y Tomioka, T Hishinuma

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　181　(4)　447-457　1997/04

DOI： 10.1620/tjem.181.447 　

ISSN： 0040-8727

eISSN： 1349-3329
Effects of haloperidol and cocaine pretreatments on brain distribution and kinetics of [C-11]methamphetamine in methamphetamine sensitized dog: Application of PET to drug pharmacokinetic study Peer-reviewed

H Nakamura, T Hishinuma, Y Tomioka, S Ishiwata, T Ido, R Iwata, Y Funaki, M Itoh, T Fujiwara, K Yanai, M Sato, Y Numachi, S Yoshida, M Mizugaki

NUCLEAR MEDICINE AND BIOLOGY　24　(2)　165-169　1997/02

DOI： 10.1016/S0969-8051(96)00204-1 　

ISSN： 0883-2897
Molecular cloning of the nemA gene encoding N-ethylmaleimide reductase from Escherichia coli Peer-reviewed

K Miura, Y Tomioka, H Suzuki, M Yonezawa, T Hishinuma, M Mizugaki

BIOLOGICAL & PHARMACEUTICAL BULLETIN　20　(1)　110-112　1997/01

DOI： 10.1248/bpb.20.110 　

ISSN： 0918-6158
Induction of IFN-gamma and IL-1 alpha production in macrophages stimulated with phosphopolysaccharide produced by Lactococcus lactis ssp cremoris Peer-reviewed

H Kitazawa, T Itoh, Y Tomioka, M Mizugaki, T Yamaguchi

INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY　31　(1-3)　99-106　1996/08

DOI： 10.1016/0168-1605(96)00968-3 　

ISSN： 0168-1605
Effects of clofibrate on flow cytometric populations in rat liver Peer-reviewed

Y Tomioka, H Suzuki, K Miura, T Yamaguchi, T Hishinuma, M Mizugaki

METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY　18　(3)　189-195　1996/04

ISSN： 0379-0355
Subcellular distribution of rat liver NADPH-2,4-dienoyl-CoA reductase Peer-reviewed

M Mizugaki, A Hirose, H Suzuki, K Miura, K Edo, Y Tomioka

BIOLOGICAL & PHARMACEUTICAL BULLETIN　19　(2)　176-181　1996/02

DOI： 10.1248/bpb.19.176 　

ISSN： 0918-6158
Positron emission tomography study of the alterations in brain distribution of [C-11]methamphetamine in methamphetamine-sensitized dog Peer-reviewed

H Nakamura, T Hishinuma, Y Tomioka, T Ido, R Iwata, Y Funaki, M Itoh, T Fujiwara, K Yanai, M Sato, Y Numachi, S Yoshida, M Mizugaki

CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE　801　401-408　1996

DOI： 10.1111/j.1749-6632.1996.tb17462.x 　

ISSN： 0077-8923
A sandwich enzynce-linked Immunosorbent Assay for △³-△²-Enoyl-CoA Isomerase in Rat-Tissue Homogenates Peer-reviewed

TOMIOKA Yoshihisa

Tohoku J. Exp. Med.　(179)　35　1996

DOI： 10.1620/tjem.179.35 　
Direct determination of serum glycyrrhetic acid by a monoclonal antibody-based inhibition ELISA using ibuprofen for releasing serum albumin-bound glycyrrhetic acid Peer-reviewed

K Itoh, M Hayasaka, M Niizeki, S Nozaki, S Ishiwata, Y Tomioka, M Mizugaki

JOURNAL OF IMMUNOASSAY　17　(4)　343-352　1996

ISSN： 0197-1522
Adsorption of Continuous Infused-G-CSF to Infusion Sets Peer-reviewed

TOMIOKA Yoshihisa

Jpn. J. Hosp. Pham.　22　(3)　230-234　1996
Publisher:
DOI： 10.5649/jjphcs1975.22.230 　

ISSN： 0389-9098

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The change in the adsorption to Infusion sets, the adsorption ratio and the recovery ratio of recombinant human granulocyte-colony stimulating factor (G-CSF) were investigated in vitro by administering a continuous intravenous infusion of G-CSF. After 250 μg of G-CSF (nartograstim) preparation was dissolved with 100 ml of sterile saline in a commercially produced polypropylene container, operating the pump ( 8 ml per hrs), the G-CSF levels in the container, in the upper part of the final filter, in the lower part of the final filter, and in the collecting vessels, were determined by enzyme-linked immunosorbent assay (ELISA) for G-CSF at various time (0, 0.5, 1, 1.5, 2, 3, 6, and 10hrs). In the first day's experiment, that is, using a new infusion set (container, line and filters) , the G-CSF levels in the upper and lower part of filter and in the collecting vessels were very low during to 0.5 to 1.5 hrs after operating. However their levels roughly recovered until the container's during 3 to 6 hrs. A marked adsorption of G-CSF was also observed not only into the container and filters but also into the line. Notably the recovery of G-CSF was improved in the second day's experiment. It is necessary for physicians to give consideration to these adsorptions and to the loss of G-CSF when a small amount of G-CSF is dissolved for treatment by continuous intravenous infusion.
POSITRON EMISSION TOMOGRAPHY (PET) STUDY OF THE ALTERATIONS IN BRAIN DISTRIBUTION OF [C-11] METHAMPHETAMINE IN METHAMPHETAMINE SENSITIZED DOG Peer-reviewed

M MIZUGAKI, H NAKAMURA, T HISHINUMA, Y TOMIOKA, S ISHIWATA, H SUZUKI, T IDO, R IWATA, Y FUNAKI, M ITOH, T FUJIWARA, K YANAI, M SATO, Y NUMACHI, S YOSHIDA

NUCLEAR MEDICINE AND BIOLOGY　22　(6)　803-807　1995/08

DOI： 10.1016/0969-8051(95)00025-S 　

ISSN： 0883-2897
THE DISTRIBUTION OF [C-11] COCAINE IN NORMAL AND COCAINE-SENSITIZATION MICE Peer-reviewed

M MIZUGAKI, T HISHINUMA, K KIMURA, H NAKAMURA, H ASO, F ISHII, M NISHIKAWA, K ITOH, Y TOMIOKA, S ISHIWATA, H MORITANI, T UYAMA, T IDO

NUCLEAR MEDICINE AND BIOLOGY　21　(6)　793-799　1994/08

DOI： 10.1016/0969-8051(94)90158-9 　

ISSN： 0883-2897
CULTURED MURINE DERMAL CELLS CAN FUNCTION LIKE THYMIC NURSE CELLS Peer-reviewed

S AIBA, S NAKAGAWA, M HARA, Y TOMIOKA, M DEGUCHI, H TAGAMI

JOURNAL OF INVESTIGATIVE DERMATOLOGY　103　(2)　162-167　1994/08

ISSN： 0022-202X
EXPRESSION OF MESSENGER-RNA ENCODING IFN-ALPHA IN MACROPHAGES STIMULATED WITH LACTOBACILLUS-GASSERI Peer-reviewed

H KITAZAWA, Y TOMIOKA, K MATSUMURA, H ASO, M MIZUGAKI, T ITOH, T YAMAGUCHI

FEMS MICROBIOLOGY LETTERS　120　(3)　315-321　1994/07

DOI： 10.1016/0378-1097(94)90490-1 　

ISSN： 0378-1097
A Human P450 Isoform Catalyzes Trp P-2 Activation Peer-reviewed

TOMIOKA Yoshihisa

Oncology (Life Sci. Adv.)　13　153　1994
IMMUNOCYTOCHEMICAL LOCALIZATION OF DELTA-3, DELTA-2-ENOYL-COA ISOMERASE AND NADPH-DEPENDENT-2,4-DIENOYL-COA REDUCTASE IN RAT-KIDNEY Peer-reviewed

S YOKOTA, Y TOMIOKA, H SUZUKI, M MIZUGAKI

HISTOCHEMISTRY　99　(6)　463-469　1993/06

ISSN： 0301-5564
DISTRIBUTION OF C-11 LABELED METHAMPHETAMINE AND THE EFFECT OF ITS CHRONIC ADMINISTRATION IN MICE Peer-reviewed

M MIZUGAKI, T HISHINUMA, H NAKAMURA, M YAMASHITA, K SHIMOMURA, K ITOH, A HIROSE, Y TOMIOKA, H ASO, K EDO, T TAKAHASHI, T IDO

NUCLEAR MEDICINE AND BIOLOGY　20　(4)　487-492　1993/05

ISSN： 0883-2897
Distribution of carbon-11 labeled methamphetamine and the effect of its chronic administration in mice Peer-reviewed

Michinao Mizugaki, Takanori Hishinuma, Hitoshi Nakamura, Masamichi Yamashita, Kohichi Shimomura, Kunihiko Itoh, Akihiko Hirose, Yoshihisa Tomioka, Hisashi Aso, Kiyoto Edo, Toshihiro Takahashi, Tatsuo Ido

Nuclear Medicine and Biology　20　(4)　487-492　1993

DOI： 10.1016/0969-8051(93)90080-E 　

ISSN： 0969-8051
Detection of heat-stable δ, δ2-enoyl-coa isomerase in rat liver mitochondria and peroxisomes by immunochemical study using specific antibody Peer-reviewed

Yoshihisa Tomioka, Kazuyuki Aihara, Akihiko Hirose, Takanori Hishinuma, Michinao Mizugaki

Journal of Biochemistry　109　(3)　394-398　1991
Publisher: Oxford University Press
DOI： 10.1093/oxfordjournals.jbchem.a123392 　

ISSN： 0021-924X
Biodistribution of 11C-methamphetamine in tissue of mice. Peer-reviewed

Edo, K, Yamashita, M, Nakamura, H, Takahashi, K, Ito, K, Tomioka, Y, Hishinuma, T, Kanno, S, Mizugaki, M, Aso, H, Takahashi, T, Ido, T

CYRIC Annual Repot　1987　115-121　1987/06
Publisher: Cyclotron and Radioisotope Center, Tohoku University
Synthesis of 11C-labeled methampheta-mine and its biodistribution in mice. Peer-reviewed

Mizugaki, M, Nakamura, H, Kimura, K, Aso,H, Ishii, F, Itoh, K, Tomioka, Y, Itoh, K, Nishikawa, M, Uyama, T, Moritani, H, Ishiwata, I, Hishinuma, I

CYRIC Annual Repot　159-163　1986/06

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Misc. 117

Development of LC-MS/MS simultaneous quantitative method for biomarker candidate compounds aimed to realize a prognostic method for renal function in diabetic kidney disease

鯨井涼太, 安部水輝, 平本航大, 渡辺匠, 鈴木千登世, 豊原敬文, 豊原敬文, 阿部高明, 阿部高明, 松本洋太郎, 富岡佳久

日本薬学会年会要旨集(Web)　144th　2024

ISSN： 0918-9823
Toll様受容体4刺激抗体は肥満細胞の炎症反応を抑制する

塚本宏樹, 小林洋平, 渡邉悠理香, 富岡佳久, 富岡佳久

日本薬学会九州山口支部大会講演要旨集(CD-ROM)　40th　2023
tRNA^His特異的酵素THG1Lが細胞のストレス応答に与える影響の検討

清水珠生, 秋山泰利, 松本洋太郎, 富岡佳久

日本薬学会東北支部大会講演要旨集　62nd　2023
ミトコンドリア病の病態解明に向けたtRNA特異的抽出法の開発

中川翔平, 渡邉麻友香, 山田明日香, 秋山泰利, 松本洋太郎, 富岡佳久

日本薬学会東北支部大会講演要旨集　62nd　2023
糖尿病性腎臓病評価法に用いる蛍光標識フェニルサルフェートの合成

熊谷知大, 小田垣水晶, 秋山泰利, 松本洋太郎, 塚本宏樹, 金光祥臣, 富岡佳久

日本薬学会東北支部大会講演要旨集　62nd　2023
糖尿病性腎臓病の腎予後予測マーカーとしてのフェニル硫酸の有用性

菊地晃一, 鯨井涼太, 松本洋太郎, 中村智洋, 渡邉駿, 三瀬広記, 豊原敬文, 鈴木健弘, 富岡佳久, 和田淳, 阿部高明

日本腎臓学会誌(Web)　65　(3)　2023

ISSN： 1884-0728
尿毒素フェニル硫酸はインスリン分泌を刺激し糖尿病性腎症におけるインスリン抵抗性を惹起する

頓宮慶泰, 笠原朋子, 川邊千陽, 鈴木健新, 菊地晃一, 三瀬広記, 鯨井涼太, 松本洋太郎, 秋山泰利, 渡邉駿, 豊原敬文, 鈴木健弘, 和田淳, 富岡佳久, 田中哲洋, 阿部高明

日本腎臓学会誌(Web)　65　(3)　2023

ISSN： 1884-0728
誘導体化を用いたLC-MS/MSアルギニン代謝物定量系の構築

浦里真莉菜, 鯨井涼太, 秋山泰利, 松本洋太郎, 渡邉駿, 阿部高明, 富岡佳久

日本薬学会東北支部大会講演要旨集　62nd　2023
糖尿病性腎症におけるインスリン分泌促進とインスリン抵抗性亢進の原因に尿毒素フェニル硫酸が存在する

頓宮慶泰, 笠原朋子, 川邊千陽, 鈴木健新, 菊地晃一, 菊地晃一, 三瀬広記, 鯨井涼太, 松本洋太郎, 秋山泰利, 鈴木千登世, 渡邉駿, 渡邉駿, 豊原敬文, 豊原敬文, 鈴木健弘, 鈴木健弘, 和田淳, 富岡佳久, 田中哲弘, 阿部高明, 阿部高明

糖尿病(Web)　66　(Suppl)　2023

ISSN： 1881-588X
Elobixibat投与マウスにおける胆汁酸および腸内細菌叢の検討

蓑輪圭太, 秋山由雅子, 笠原朋子, 何欣蓉, 前川正充, 菊池晃一, 豊原敬文, 鈴木健弘, 鈴木千登世, 鯨井涼太, 松本洋太郎, 富岡佳久, 阿部高明

日本腎臓学会誌(Web)　65　(3)　2023

ISSN： 1884-0728
Toll様受容体4刺激抗体の食物アレルギー予防・治療効果

塚本宏樹, 小林洋平, 渡邉悠理香, 富岡佳久, 富岡佳久

日本薬学会九州山口支部大会講演要旨集(CD-ROM)　39th　2022
修飾核酸特異的抗体を用いたストレス反応性RNA修飾のスクリーニング

竹中慶香, 秋山泰利, 松本洋太郎, 富岡佳久

日本薬学会東北支部大会講演要旨集　60th　2021
標的分子を内在化し分解誘導する二重特異性抗体の機能評価

西田健人, 山崎晶貴, 秋山泰利, 松本洋太郎, 富岡佳久, 益子高

日本薬学会東北支部大会講演要旨集　60th　2021
細胞外小胞を介したCD73のがん病態に与える影響の評価

山田愛梨香, 秋山泰利, 松本洋太郎, 富岡佳久

日本薬学会東北支部大会講演要旨集　60th　2021
Quantitative analysis of gut microbiota-derived metabolites by LC-MS sheds light on the gut-kidney axis on kidney disease

金光祥臣, 三島英換, 松本洋太郎, 前川正充, 前川正充, 菊地晃一, 三枝大輔, 阿部高明, 阿部高明, 眞野成康, 眞野成康, 富岡佳久

JSBMS Letters　46　(Supplement)　2021

ISSN： 1881-5464
腸内細菌叢と胆汁酸の調節による腎不全治療

秋山由雅子, 前川正充, 菊地晃一, 何欣蓉, 一條真梨子, 鈴木千登世, 渡邉駿, 豊原敬文, 鈴木健弘, 富岡佳久, 阿部高明

日本腎臓学会誌(Web)　63　(4)　2021

ISSN： 1884-0728
Toll様受容体4刺激抗体の肥満細胞抑制作用

渡邉悠理香, 塚本宏樹, 塚本宏樹, 小林洋平, 富岡佳久

日本薬学会東北支部大会講演要旨集　59th　2020
糖尿病性腎症の発症・進展予測マーカーとしてのフェニル硫酸の有用性

菊地晃一, 三枝大輔, 金光祥臣, 松本洋太郎, 三瀬広記, 中村智洋, 三島英換, 豊原敬文, 鈴木健弘, 寳澤篤, 和田淳, 富岡佳久, 阿部高明

日本腎臓学会誌(Web)　62　(4)　2020

ISSN： 1884-0728
アデニン誘発腎不全マウスにおけるエロビキシバットの効果

秋山由雅子, 前川正充, 金光祥臣, 菊地晃一, 何欣蓉, 三島英換, 鈴木健弘, 一條真梨子, 鈴木千登世, 眞野成康, 富岡佳久, 阿部高明

日本腎臓学会誌(Web)　62　(4)　2020

ISSN： 1884-0728
修飾核酸一斉定量系を用いたCOPD早期発見手法の開発検討

渡辺匠, 平本航大, 沼倉忠久, 滝田克也, 宮内栄作, 突田容子, 杉浦久敏, 松本洋太郎, 富岡佳久

日本薬学会東北支部大会講演要旨集　59th　2020
胆汁酸トランスポーター阻害薬エロビキシバットによる腎保護作用の検討

秋山由雅子, 何欣蓉, 金光祥臣, 前川正充, 菊地晃一, 鈴木健弘, 三島英換, 一條真梨子, 鈴木千登世, 眞野成康, 富岡佳久, 伊藤貞嘉, 阿部高明

日本腎臓学会誌　61　(3)　403　2019/05/15

ISSN： 0385-2385
透析におけるルビプロストンの尿毒素に対する効果

尾形佳昭, 金井秀明, 金塚完, 中嶋俊之, 鈴木千登世, 淺地圭, 金光祥臣, 松本洋太郎, 富岡佳久, 阿部高明

日本腎臓学会誌　61　(3)　381-381　2019/05/15
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385

eISSN： 1884-0728
質量分析計によるヒト肝がん浸潤バイオマーカー探索

三枝大輔, 三枝大輔, 三枝大輔, 永井滉士, URANBILEG Baasanjav, URANBILEG Baasanjav, 蔵野信, 蔵野信, 池田均, 池田均, 矢冨裕, 矢冨裕, 富岡佳久, 青木淳賢, 青木淳賢

日本緩和医療薬学会年会プログラム・要旨集　13th　2019
修飾核酸の高精度一斉定量系の構築

平本航大, 松本洋太郎, 塚本宏樹, 富岡佳久

日本薬学会東北支部大会講演要旨集　57th　69　2018/10/05
疾患関連リゾリン脂質の臨床診断マーカーへの応用 High-Definition Mass Spectrometryによるヒト肝がん組織のメタボロミクス解析

三枝大輔, 永井滉士, Uranbileg Baasanjav, 蔵野信, 長谷川潔, 國土典宏, 池田均, 矢冨裕, 富岡佳久, 青木淳賢

JSBMS Letters　43　(Suppl.)　64-64　2018/08
Publisher: (一社)日本医用マススペクトル学会
ISSN： 1881-5464
グアニル酸シクラーゼC受容体作動薬リナクロチドは腎不全に伴う腸内環境悪性化を改善し腎線維化を抑制する

南都文香, 福田真嗣, 金光祥臣, 三枝大輔, 菊地晃一, 何欣蓉, 三島英換, 鈴木健弘, 松橋徹郎, 及川義嗣, 鈴木千登世, 富岡佳久, 曽我朋義, 伊藤貞嘉, 阿部高明

日本腎臓学会誌　60　(3)　463-463　2018/04/30
Publisher: (一社)日本腎臓学会
ISSN： 0385-2385
LPS‐binding proteinはリポ多糖によるCD14依存的Toll様受容体4内在化を媒介しTRIFシグナルを制御する

塚本宏樹, 武内偲乃, 久保田佳苗, 小坂井沙緒, 紫竹歩, 鵜飼一歩, 小林洋平, 大久保美咲, 沼崎宗夫, 金光祥臣, 松本洋太郎, 野地智法, 渡邊康一, 麻生久, 富岡佳久

日本生化学会大会(Web)　90th　ROMBUNNO.2LBA‐013 (WEB ONLY)-013]　2017/12
Publisher: 生命科学系学会合同年次大会運営事務局
LPS-binding proteinはリポ多糖によるCD14依存的Toll様受容体4内在化を媒介し、TRIFシグナルを制御する

塚本宏樹, 武内偲乃, 久保田佳苗, 小坂井沙緒, 紫竹歩, 鵜飼一歩, 小林洋平, 大久保美咲, 沼崎宗夫, 金光祥臣, 松本洋太郎, 野地智法, 渡邊康一, 麻生久, 富岡佳久

生命科学系学会合同年次大会　2017年度　[2LBA-013]　2017/12
Publisher: 生命科学系学会合同年次大会運営事務局
An inhibitory epitope of human Toll-like receptor 4 resides on leucine-rich repeat 13 and is recognized by a monoclonal antibody (vol 591, pg 2406, 2017)

Hiroki Tsukamoto, Yuki Yamagata, Ippo Ukai, Shino Takeuchi, Misaki Okubo, Yohei Kobayashi, Sao Kozakai, Kanae Kubota, Muneo Numasaki, Yoshitomi Kanemitsu, Yotaro Matsumoto, Yoshihisa Tomioka

FEBS LETTERS　591　(18)　2953-2953　2017/09

DOI： 10.1002/1873-3468.12837 　

ISSN： 1873-3468
LPS-binding proteinはToll様受容体4の二量体化・内在化を介してTRIF依存的IKKε/TBK1/IRF3経路を活性化する

久保田佳苗, 武内偲乃, 鵜飼一歩, 小坂井沙緒, 金光祥臣, 松本洋太郎, 塚本宏樹, 富岡佳久

日本薬学会年会要旨集　137年会　(3)　76-76　2017/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
異なるシグナル誘導活性を持つToll様受容体4刺激抗体による抗原特異的抗体産生抑制効果

小林洋平, 小坂井沙緒, 久保田佳苗, 武内偲乃, 金光祥臣, 松本洋太郎, 塚本宏樹, 富岡佳久

日本薬学会年会要旨集　137年会　(3)　138-138　2017/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
ヒトToll様受容体4活性化に必要なleucine-rich repeat 13は抑制抗体によって認識される

山形由貴, 大久保美咲, 鵜飼一歩, 金光祥臣, 松本洋太郎, 塚本宏樹, 富岡佳久

日本薬学会年会要旨集　137年会　(3)　142-142　2017/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
サイクリックADPリボース安定同位体の合成

齋藤一樹, 田中晃佑, 鈴木千登世, 阿部高明, 金光祥臣, 塚本宏樹, 松本洋太郎, 富岡佳久

日本薬学会年会要旨集　137年会　(2)　156-156　2017/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
LC-MSを用いた細胞内サイクリックADPリボース高感度定量法の構築

齋藤一樹, 金光祥臣, 田中晃佑, 鈴木千登世, 阿部高明, 塚本宏樹, 松本洋太郎, 富岡佳久

日本薬学会年会要旨集　137年会　(2)　246-246　2017/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
LC‐HDMSおよびIMSを用いたヒト肝癌組織メタボロミクスによる新規バイオマーカーの同定

永井滉士, 三枝大輔, 三枝大輔, 山崎貴広, 金光祥臣, 塚本宏樹, 池田均, 矢冨裕, 松本洋太郎, 富岡佳久

日本薬学会東北支部大会講演要旨集　56th　58　2017
不活性型二量体構造の誘導を介した抑制型ヒトToll様受容体4抗体の新規作用機序

山形由貴, 鵜飼一歩, 金光祥臣, 小林洋平, 松本洋太郎, 塚本宏樹, 富岡佳久

日本薬学会年会要旨集(CD-ROM)　137th　ROMBUNNO.25X‐pm03S　2017
ミックスドモードODSカラムを用いたLC‐MS/MSによる尿毒症物質一斉定量系の構築

金光祥臣, 淺地圭, 松本洋太郎, 塚本宏樹, 三枝大輔, 阿部高明, 富岡佳久

日本薬学会東北支部大会講演要旨集　56th　58　2017
Toll様受容体4シグナルによるGr1⁺CD11b⁺細胞誘導を介した抗原特異的抗体産生抑制機序

小坂井沙緒, 小林洋平, 金光祥臣, 松本洋太郎, 塚本宏樹, 富岡佳久

日本薬学会年会要旨集(CD-ROM)　137th　ROMBUNNO.26X‐am02S　2017
イナビルによるアナフィラキシー症例報告と添加乳糖に夾雑するアレルゲン乳タンパク質の同定

金光祥臣, 金光祥臣, 森川みき, 塚本宏樹, 塚本宏樹, 松本洋太郎, 松本洋太郎, 森川昭正, 富岡佳久, 富岡佳久

日本医療薬学会年会講演要旨集(Web)　26　2016

ISSN： 2424-2470
In vitroとin vivoにおける、Rho/MAL/SRF経路を介したV-1遺伝子による黒質線条体のドーパミン系の機能の調節(In vitro and in vivo regulation of the nigrostriatal dopaminergic function by V-1 gene via the Rho/MAL/SRF pathway)

川畑伊知郎, 来延新, 大宅史織, 森田淳一, 加藤茂樹, 田渕明子, 福地守, 津田正明, 大橋一正, 水野健作, 泉安彦, 久米利明, 赤池昭紀, 富岡佳久, 一瀬千穂, 一瀬宏, 小林和人, 山國徹

パーキンソン病・運動障害疾患コングレスプログラム・抄録集　9回　66-66　2015/10
Publisher: Movement Disorder Society of Japan (MDSJ)
V-1遺伝子によるアクチン重合依存的な黒質線条体ドパミン生合成酵素群の統合的新規発現制御機構

川畑伊知郎, 延新来, 大宅史織, 森田淳一, 加藤茂樹, 富岡佳久, 田渕明子, 福地守, 津田正明, 一瀬-鷲見千穂, 近藤一直, 泉安彦, 久米利明, 赤池昭紀, 大橋一正, 水野健作, 一瀬宏, 小林和人, 山国徹

第37回日本神経科学大会 Neuroscience2014　2014/09
V-1によるアクチン重合依存的な黒質線条体ドパミン生合成酵素群の統合的新規発現制御機構

川畑伊知郎, 延新来, 大宅史織, 森田淳一, 加藤茂樹, 田渕明子, 福地守, 津田正明, 大橋一正, 水野健作, 泉安彦, 久米利明, 赤池昭紀, 富岡佳久, 一瀬(鷲見) 千穂, 近藤一直, 一瀬宏, 小林和人, 山國徹

第87回日本薬理学会年会　2014/03
11種のCYP4A11および3種のCYP4F2遺伝子多型バリアントにおける酵素活性変化

齋藤雄大, 三枝大輔, 鈴木直人, 富岡佳久, 平澤典保, 平塚真弘

日本薬学会年会要旨集　134年会　(3)　62-62　2014/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
シースレスインターフェイスを用いたCE-MSによる低分子化合物分析法の検討

陣野大輔, 齋藤一樹, 由利謙典, 武川力永, 塚本宏樹, 鈴木直人, 阿部高明, 富岡佳久

日本薬学会東北支部大会講演要旨集　53rd　2014
PTX療法におけるラニチジン注とファモチジン注のアレルギー発現率の後方視的コホート研究

片岡佑太, 菊地正史, 中川直人, 木皿重樹, 高橋哉子, 小笠原喜美代, 我妻恭行, 久道周彦, 鈴木直人, 村井ユリ子, 富岡佳久, 石岡千加史, 島田美樹, 眞野成康

日本病院薬剤師会雑誌　49　(10)　1091-1095　2013/10
Publisher: (一社)日本病院薬剤師会
ISSN： 1341-8815
日-10-O40-25 東北大学薬学研究科4年制博士課程におけるスーパージェネラリスト・ファーマシスト養成教育の試み : 医学部臨床修練への参加(薬学教育(実務実習・その他)、卒後研修・研修制度,一般演題(口頭)40,再興、再考、創ろう最高の医療の未来)

瀬川良佑, 高橋亜希, 平塚真弘, 眞野成康, 富岡佳久, 佐藤博, 平澤典保

日本医療薬学会年会講演要旨集　23　245-245　2013/08/28
Publisher: 日本医療薬学会
土-P3-407 乳癌FEC100療法におけるホスアプレピタント注の有効性と安全性の検討(がん薬物療法(制吐支持療法),ポスター発表,一般演題,再興、再考、創ろう最高の医療の未来)

渡邊桂子, 菊地正史, 木皿重樹, 小笠原喜美代, 久道周彦, 石田孝宣, 鈴木直人, 村井ユリ子, 島田美樹, 富岡佳久, 石岡千加史, 眞野成康

日本医療薬学会年会講演要旨集　23　319-319　2013/08/28
Publisher: 日本医療薬学会
PTX前投薬におけるラニチジン注とファモチジン注によるアレルギー発現率の比較

片岡佑太, 菊地正史, 中川直人, 木皿重樹, 高橋哉子, 小笠原喜美代, 我妻恭行, 久道周彦, 鈴木直人, 村井ユリ子, 富岡佳久, 石岡千加史, 島田美樹, 眞野成康

医薬品相互作用研究　37　(1)　84-84　2013/08
Publisher: 医薬品相互作用研究会
ISSN： 0385-5015
LysoPSの検出系の確立と生体内におけるLysoPSの検出

奥平倫世, 井上飛鳥, 三枝大輔, 富岡佳久, 巻出久美子, 青木淳賢

脂質生化学研究　55　128-130　2013/05
Publisher: 日本脂質生化学会
ISSN： 0285-1520
がん化学療法におけるドーパミン生合成酵素の遺伝子発現変化と制吐療法ガイドラインによる催吐リスク分類との相関

大宅史織, 川畑伊知郎, 福田周, 田代匠, 鈴木直人, 山國徹, 富岡佳久

日本薬学会年会要旨集　133年会　(4)　181-181　2013/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
ヒト肝細胞癌細胞株HepG2に対する鉄キレート剤デフェロキサミンの作用機序解明に向けた非標的メタボローム解析

杉山栄二, 鈴木直人, 福田周, 大宅史織, 中曽根正皓, 大内麻由, 三枝大輔, 川畑伊知郎, 山國徹, 富岡佳久

日本薬学会年会要旨集　133年会　(4)　186-186　2013/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
V-1によるアクチン重合促進を介したMAL/SRF依存的なチロシン水酸化酵素の新規発現制御機構

川畑伊知郎, 大宅史織, 来延新, 森田淳一, 田渕明子, 津田正明, 一瀬宏, 加藤茂樹, 小林和人, 泉安彦, 久米利明, 赤池昭紀, 富岡佳久, 山國徹

日本薬学会年会要旨集　133年会　(3)　187-187　2013/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
LC/ESI-MSを用いた血清胸腺因子(FTS)定量法の開発

中曽根正皓, 鈴木直人, 金光祥臣, 塚本宏樹, 富岡佳久

日本薬学会東北支部大会講演要旨集　52nd　2013
新規腎障害マーカーとしての1-メチルアデノシンの検討

陣野大輔, 鈴木直人, 津久井佑梨, 三枝大輔, 三島英換, 鈴木千登世, 塚本宏樹, 阿部高明, 富岡佳久

日本薬学会東北支部大会講演要旨集　52nd　2013
バイタルサイン実習:高機能患者シミュレータを用いた疾患模擬処置を「見学型」から「実践型」に切り替えたことによる学生の学習意欲調査

橋本貴尚, 高橋信行, 佐藤恵美子, 村井ユリ子, 平澤典保, 富岡佳久, 栃窪克行, 佐藤博

日本医療薬学会年会講演要旨集　22nd　484　2012/10/10
LC/MS/MSを用いたスフィンゴシン-1-リン酸の超高感度分析法について

高橋友大, 三枝大輔, 陣野大輔, 井上飛鳥, 奥谷倫代, 青木淳賢, 鈴木直人, 富岡佳久

JSBMS Letters　37　(Suppl.)　65-65　2012/09
Publisher: (一社)日本医用マススペクトル学会
ISSN： 1881-5464
LC/MS/MSを用いたマウス脳組織中スフィンゴシン一リン酸の超高感度定量分析について

三枝大輔, 高橋友大, 大宅史織, 井上飛鳥, 奥谷倫代, 鈴木直人, 眞野成康, 青木淳賢, 富岡佳久

JSBMS Letters　37　(Suppl.)　66-66　2012/09
Publisher: (一社)日本医用マススペクトル学会
ISSN： 1881-5464
生体内におけるリゾホスファチジルセリンの検出

奥谷倫世, 井上飛鳥, 巻出久美子, 三枝大輔, 富岡佳久, 青木淳賢

日本薬学会年会要旨集　132年会　(3)　121-121　2012/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
LC/MS/MSを用いた生体試料中スフィンゴ脂質同時定量法の構築

芝可奈子, 三枝大輔, 井上飛鳥, 濱弘太郎, 奥谷倫世, 鈴木千登世, 佐藤恵美子, 眞野成康, 菱沼隆則, 鈴木直人, 佐藤博, 阿部高明, 青木淳賢, 富岡佳久

日本薬学会年会要旨集　132年会　(4)　138-138　2012/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
胆汁酸トランスポーターSLC10A4の機能解析

阿部拓哉, 金光祥臣, 中曽根正皓, 川畑伊知郎, 山國徹, 中島晶, 鈴木直人, 西川正純, 菱沼隆則, 富岡佳久

日本薬学会年会要旨集　132年会　(4)　271-271　2012/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
LC/MS/MSを用いたアルギニン代謝関連物質定量分析系の構築

三枝大輔, 石田綾子, 菅原大貴, 鈴木直人, 阿部高明, 富岡佳久

日本腎臓学会誌　54　(3)　2012

ISSN： 0385-2385
オキサリプラチン誘発性末梢神経障害の発生因子と発生予測式の臨床薬剤学的応用性の検証

田中敏, 田中敏, 三村亨, 黒澤真帆, 村井ユリ子, 三枝大輔, 鈴木直人, 蒲生真紀夫, 佐藤益男, 富岡佳久

日本薬学会年会要旨集　132nd　(4)　2012

ISSN： 0918-9823
オキサリプラチン誘発性末梢神経障害に関する発現予測式の臨床薬剤学的応用性の検証

田中敏, 田中敏, 鈴木直人, 三村亨, 黒澤真帆, 村井ユリ子, 三枝大輔, 杉山克郎, 蒲生真紀夫, 佐藤益男, 富岡佳久

日本臨床腫瘍学会学術集会プログラム・抄録集　10th　2012
甘草成分リコカルコンのウサギ血小板凝集抑制作用

奥田亜沙, 岩下真也, 小原祐太郎, 小原祐太郎, 菅原大貴, 田代匠, 三枝大輔, 富岡佳久, 守屋孝洋, 石井邦明, 中畑則道

次世代を担う創薬・医療薬理シンポジウムプログラム・要旨集　2012　2012
抗マラリア薬アーテメーター代謝におけるCYP2B6遺伝子多型バリアントの機能解析

平塚真弘, 本田雅志, 三枝大輔, 鈴木直人, 富岡佳久, 平澤典保

臨床薬理　42　(Suppl.)　S245-S245　2011/10
Publisher: (一社)日本臨床薬理学会
ISSN： 0388-1601

eISSN： 1882-8272
薬学生の臨床思考を醸成し実務実習へとつなげる事前実習の成果と課題 : バイタル・心肺蘇生・副作用管理(一般演題(口頭)27,薬学教育(実務実習)(1),Enjoy Pharmacists' Lifestyles)

寺田志保, 橋本貴尚, 大久保孝義, 高橋信行, 村井ユリ子, 佐藤慶子, 目時弘仁, 菊谷昌浩, 平澤典保, 富岡佳久, 大庭正敏, 今井潤, 佐藤博

日本医療薬学会年会講演要旨集　21　162-162　2011/09/09
Publisher: 日本医療薬学会
生理活性リゾリン脂質の定量系の開発と産生機構の解析

井上飛鳥, 奥谷倫世, 三枝大輔, 奥平真一, 鈴木直人, 富岡佳久, 青木淳賢

日本生化学会大会プログラム・講演要旨集　84回　3P-0068　2011/09
Publisher: (公社)日本生化学会
ニコチン連続投与により誘発されるNMDA受容体サブユニットNR2Bのリン酸化とその機能的役割の解析

中島晶, 衣笠由香莉, 鳥居潤, 永井拓, 富岡佳久, 菱沼隆則, 山國徹, 山田清文

日本アルコール・薬物医学会雑誌　46　(4)　134-134　2011/08
Publisher: (一社)日本アルコール・アディクション医学会
ISSN： 1341-8963
LC/MS/MSを用いた脂質関連物質分離分析系の構築

三枝大輔, 芝可奈子, 井上飛鳥, 濱弘太郎, 青木淳賢, 鈴木直人, 富岡佳久

JSBMS Letters　36　(Suppl.)　71-71　2011/08
Publisher: (一社)日本医用マススペクトル学会
ISSN： 1881-5464
LC-ESI-MS/MSを用いた生理活性リゾリン脂質の定量系の開発

井上飛鳥, 奥谷倫世, 三枝大輔, 奥平真一, 鈴木直人, 富岡佳久, 青木淳賢

日本薬学会年会要旨集　131年会　(3)　114-114　2011/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
培養海馬ニューロンを用いたノビレチン含有国産柑橘類果皮エキスによるCRE依存的転写活性上昇作用の解析

川畑伊知郎, 平田貴大, 鐵尚美, 中嶌輝子, 小川一紀, 大泉康, 三枝大輔, 一瀬宏, 富岡佳久, 山國徹

日本薬学会年会要旨集　131年会　(3)　181-181　2011/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
脳局在型胆汁酸トランスポーターの機能解析

阿部拓哉, 金光祥臣, 中曽根正皓, 中島晶, 鈴木直人, 菱沼隆則, 富岡佳久

次世代を担う若手ファーマ・バイオフォーラム講演要旨集　10th　2011
HPLC/PDA法を用いた体内動態解析による抗アルツハイマー病天然薬物ノビレチンの脳内移行の証明

三枝大輔, 中島晶, 鐵尚美, 澁谷正俊, 山越博幸, 岩渕好治, 横須賀章人, 指田豊, 三巻祥浩, 永沼章, 大泉康, 大泉康, 大泉康, 富岡佳久, 山國徹

日本薬学会年会要旨集　131st　(4)　2011

ISSN： 0918-9823
オキサリプラチン誘発性末梢神経障害の発現頻度・重篤度予測因子の探索

三村享, 田中敏, 田中敏, 三枝大輔, 鈴木直人, 村井ユリ子, 村井ユリ子, 蒲生真紀夫, 佐藤益男, 富岡佳久

日本薬学会年会要旨集　131st　(4)　2011

ISSN： 0918-9823
オキサリプラチン誘発性末梢神経障害と生体中グアニジノコハク酸濃度変化による影響

三枝大輔, 石田綾子, 高橋舞, 芝可奈子, 菅原大貴, 津久井佑梨, 山岸佑輔, 三村享, 鈴木直人, 富岡佳久

日本薬学会年会要旨集　131st　(4)　2011

ISSN： 0918-9823
生体内transアコニット酸生成機構解明のための有機酸高感度定量法の確立

松本周平, 三枝大輔, 竹田千尋, 鈴木直人, 澁谷正俊, 岩渕好治, 富岡佳久

日本薬学会年会要旨集　131st　(4)　2011

ISSN： 0918-9823
ヒト小脳由来TE671細胞におけるプロテアーゼ活性化トランスポーターの機能解析

阿部拓哉, 中島晶, 金光祥臣, 三枝大輔, 鈴木直人, 富岡佳久, 菱沼隆則

日本薬学会年会要旨集　131st　(4)　2011

ISSN： 0918-9823
オキサリプラチン誘発性末梢神経障害発現頻度・重篤度に関連する因子

田中敏, 田中敏, 三村亨, 黒澤真帆, 村井ユリ子, 村井ユリ子, 三枝大輔, 鈴木直人, 蒲生真紀夫, 佐藤益男, 富岡佳久

日本臨床腫瘍学会学術集会プログラム・抄録集　9th　2011
次世代型専門薬剤師育成を目指した東北大学病院における大学院教育

鈴木直人, 木皿重樹, 村井ユリ子, 村井ユリ子, 黒澤真帆, 大内麻由, 三枝大輔, 眞野成康, 眞野成康, 富岡佳久

日本薬学会東北支部大会講演要旨集　50th　2011
LC/MS/MSを用いたADMA及びSDMA分離分析系の構築並びに化合物生体組織分布の解明

高橋舞, 三枝大輔, 石田綾子, 芝可奈子, 金光祥臣, 有馬直明, 濱弘太郎, 山國徹, 青木淳賢, 鈴木直人, 富岡佳久

日本薬学会東北支部大会講演要旨集　50th　2011
Ion pair LC/MS/MSによるTCA回路化合物の高感度一斉定量分析系の構築

竹田千尋, 三枝大輔, 松本周平, 阿部高明, 鈴木直人, 富岡佳久

日本薬学会東北支部大会講演要旨集　50th　2011
ノビレチン高含有陳皮エキスの抗認知症作用とその作用メカニズム

山國徹, 中島晶, 大坂直哉, 三枝大輔, 富岡佳久, 永沼明, 吉田雅昭, 松崎健太郎, 大泉康, 横須賀章人, 指田豊, 三巻祥浩

日本生薬学会年会講演要旨集　58th　2011

ISSN： 0919-1992
地域薬局における慢性腎臓病に対する食での取り組み

崎野健一, 崎野健一, 尾崎敦子, 尾形みなみ, 小林満, 岩倉大介, 星友典, 金光祥臣, 山岸祐輔, 三枝大輔, 山家靖, 山家靖, 鈴木直人, 大野武, 大野武, 富岡佳久

日本薬学会年会要旨集　131st　(4)　2011

ISSN： 0918-9823
LC/MS/MSを用いたOATP1B3の絶対定量と過剰発現細胞のプロテオーム解析

金光祥臣, 阿部拓哉, 中曽根正皓, 三枝大輔, 菱沼隆則, 鈴木直人, 富岡佳久

日本薬学会年会要旨集　131st　(4)　2011

ISSN： 0918-9823
LC-ESI-MS/MSをリゾリン脂質定量系の開発

井上飛鳥, 三枝大輔, 奥谷倫世, 鈴木直人, 富岡佳久, 青木淳賢

日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　83回・33回　4T15-1　2010/12
Publisher: (公社)日本生化学会
LC-ESI-MS/MSを用いたリゾホスファチジルセリンおよびリゾホスファチジルスレオニンの検出

奥谷倫世, 井上飛鳥, 巻出久美子, 三枝大輔, 富岡佳久, 青木淳賢

日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　83回・33回　3P-0130　2010/12
Publisher: (公社)日本生化学会
LC-ESI-MS/MSを用いたリゾリン脂質定量系の開発

井上飛鳥, 小野めぐみ, 三枝大輔, 奥谷倫世, 奥平真一, 鈴木直人, 富岡佳久, 青木淳賢

脂質生化学研究　52　187-190　2010/05
Publisher: 日本脂質生化学会
ISSN： 0285-1520
CapZを介したV-1によるチロシン水酸化酵素遺伝子発現の新規調節メカニズムの解析

森田淳一, 金京梅, 中島晶, 阿部誠也, 山岸佑輔, 陳嘉俊, 大泉康, 富岡佳久, 山國徹

日本薬学会年会要旨集　130年会　(3)　69-69　2010/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
学生用実習ワークシートを活用するSP参加型実習の評価:フィードバック内容の分析と今後の課題

小澤実香, 鈴木直人, 富澤崇, 富澤崇, 長谷川哲也, 竹平理恵子, 河合洋, 松本かおり, 神谷貞浩, 秋葉真由美, 佐田宏子, 山村重樹, 富岡佳久, 小嶋文良

日本医療薬学会年会講演要旨集　20th　(0)　385-385　2010
Publisher: 一般社団法人日本医療薬学会
DOI： 10.20825/amjsphcs.20.0_385_4 　
次世代型専門薬剤師育成を目指した大学院教育プログラムの開発-がん化学療法処方設計支援基礎実習カリキュラムの構築

鈴木直人, 金光祥臣, 松本周平, 三村享, 三枝大輔, 村井ユリ子, 村井ユリ子, 久道周彦, 佐藤真由美, 齊藤直美, 木皿重樹, 眞野成康, 眞野成康, 富岡佳久

日本薬学会年会要旨集　130th　(4)　2010

ISSN： 0918-9823
ZIC-HILICカラムを用いたロイコボリン及びメトトレキサートの分離分析系の構築

陣野大輔, 桐原誠, 三枝大輔, 高橋舞, 芝可奈子, 田中敏, 村井ユリ子, 鈴木直人, 富岡佳久

日本薬学会東北支部大会講演要旨集　49th　2010
LC-ESI-MS-MSを用いたリゾホスファチジルセリンの検出

奥谷倫世, 井上飛鳥, 巻出久美子, 三枝大輔, 富岡佳久, 青木淳賢, 青木淳賢

日本薬学会東北支部大会講演要旨集　49th　2010
アコニット酸関連物質の高感度定量系の確立

松本周平, 三枝大輔, 高橋舞, 芝可奈子, 金子達, 杉山英二, 鈴木直人, 富岡佳久

日本薬学会東北支部大会講演要旨集　49th　2010
アルギニン代謝産物一斉分析系の構築

三枝大輔, 高橋舞, 石田綾子, 芝可奈子, 田中敏, 鈴木直人, 富岡佳久

日本薬学会東北支部大会講演要旨集　49th　2010
次世代型専門薬剤師育成を目指した東北大学病院化学療法センターにおける大学院教育

鈴木直人, 村井ユリ子, 村井ユリ子, 三枝大輔, 木皿重樹, 眞野成康, 眞野成康, 富岡佳久

日本薬学会東北支部大会講演要旨集　49th　2010
次世代型専門薬剤師育成を目指した大学院教育プログラムの開発(その1)

富岡佳久, 平澤典保, 眞野成康, 村井ユリ子, 鈴木直人, 三枝大輔, 平塚真弘, 高橋亜希, 島田美樹, 岡芳知, 伊藤貞嘉, 石岡千加史, 寺崎哲也, 永沼章

日本医療薬学会年会講演要旨集　19th　469　2009/09/15
新生児マウスにおけるtetrabromobisphenol A投与による行動変化及び脳蓄積性に対する定量的解析

三枝大輔, 中島晶, 鐵尚美, 山國徹, 菱沼隆則, 富岡佳久

日本薬学会年会要旨集　129年会　(3)　262-262　2009/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
Guanidinosuccinic acid及び関連化合物のLC/MS/MSを用いた定量系の確立

三枝大輔, 金子達, 松本周平, 芝可奈子, 高橋舞, 鈴木直人, 富岡佳久

日本薬学会東北支部大会講演要旨集　48th　2009
PC12D細胞における抑肝散加陳皮半夏エキスのERK/CREBシグナル伝達の活性化作用

桐生嘉浩, 中島晶, 三枝大輔, 吉田雅昭, 富岡佳久, 大泉康, 大泉康, 大泉康, 山國徹

日本薬学会年会要旨集　129th　(3)　2009

ISSN： 0918-9823
研究費報告書平成17年度学長所管研究奨励金交付に伴う研究成果報告書 GVHDの個別治療に向けたモデル細胞を用いたバイオマーカーの探索研究

富岡佳久, 鈴木直人, 小澤実香

城西国際大学紀要　15　(4)　33-40　2007/03
Publisher: 城西国際大学
ISSN： 0919-4967
Mechanisms of mucin production by rhinovirus infection in cultured human airway epithelial cells.

Inoue Daisuke, Yamaya Mutsuo, Kubo Hiroshi, Sasaki Takahiko, Hosoda Masayoshi, Numasaki Muneo, Tomioka Yoshihisa, Yasuda Hiroyasu, Sekizawa Kiyohisa, Nishimura Hidekazu, Sasaki Hidetada

Respir Physiol Neurobiol　154　(3)　484-499　2006
Publisher: Elsevier BV
DOI： 10.1016/j.resp.2005.11.006 　

ISSN： 1569-9048
Preparation of neocarzinostatin apoprotein mutants and the randomized library on the chromophore-binding cavity.

Tomioka Yoshihisa, Kisara Shigeki, Yoshizawa Saki, Ozawa Mika, Suzuki Naoto, Yamaguchi Hiroaki, Hishinuma Takanori, Mizugaki Michinao, Goto Junichi

Biol Pharm Bull　29　(5)　1010-1014　2006
Publisher: The Pharmaceutical Society of Japan
DOI： 10.1248/bpb.29.1010 　

ISSN： 0918-6158 1347-5215

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W39F, F52Y, S98G, S98A, and S98C mutants of the neocarzinostatin apoprotein (apo-NCS) were newly prepared and investigated their physicochemical properties. The circular dichroism (CD) spectra of F78W, F52Y, S98A, S98G, S98C were superimposable with that of wild type 1R49 protein although the minor spectral change seemed to be in the ellipticity of W39F. The results suggest that position 52, 78, and 98 involving natural chromophore binding do not play a major role in the inducing overall structural changes of the protein. Conversely, the position 39 would be affected slightly. Ethidium bromide (EtdBr) binding to mutants was also evaluated by the monitoring of total fluorescence intensity and fluorescence polarization (FP). The observed dissociation constant in the FP study was 4.4 μM for wild type, 2.2 μM for S98A, 1.3 μM for S98G, 9.7 μM for S98C, respectively. When S98G and F52Y, the calculated maximum change of the total fluorescence intensity was increased, suggesting that the EtdBr binding to S98G or F52Y were slightly improved compared with the wild type. Then, a total of 14 amino acids randomly substituted phage displayed library of apo-NCS was successfully prepared, because substitution of the amino acid structured the chromophore-binding cavity were not change the overall structural features. The phages which bound glycyrrhetic acid conjugated bovine serum albumin were enriched from this library using phage display technique as the pilot experiments. Although more precision investigation still needs, it should be possible to select variants that have new functions not found in nature.
LST-2膜外ドメインに対するモノクローナル抗体の性状解析

石川陽菜, 菱沼隆則, 岡田匡弘, 三日市剛, 鈴木直人, 富岡佳久, 海野倫明, 阿部高明, 後藤順一

日本薬学会年会要旨集　125th　(2)　2005

ISSN： 0918-9823
The induction of prostaglandin E synthase and upregulation of cyclooxygenase-2 by 9-cis retinoic acid

H Tsukamoto, T Hishinuma, R Tayama, K Narahara, N Suzuki, Y Tomioka, J Goto

PROSTAGLANDINS & OTHER LIPID MEDIATORS　74　(1-4)　61-74　2004/10

DOI： 10.1016/j.prostaglandins.2004.07.001 　

ISSN： 0090-6980
Thiazolidinediones increase arachidonic acid release and subsequent prostanoid production in a peroxisome proliferator-activated receptor gamma-independent manner

H Tsukamoto, T Hishinuma, N Suzuki, R Tayama, M Hiratsuka, Y Tomioka, M Mizugaki, J Goto

PROSTAGLANDINS & OTHER LIPID MEDIATORS　73　(3-4)　191-213　2004/04

DOI： 10.1016/j.prostaglandins.2004.01.008 　

ISSN： 0090-6980
Effect of peroxisome proliferator-activated receptor gamma on thromboxane A(2) and prostaglandin E(2) production in macrophage cell lines.

YAMAZAKI T, YOKOO T, TOMIOKA Y, SUZUKI H, HISHINUMA T, MIZUGAKI M

Prostaglandins Leukot Essent Fatty Acids　67　(4)　245-251　2002

DOI： 10.1054/plef.2002.0426 　

ISSN： 0952-3278
Real-Time PCRを用いた薬物療法に影響を与えるSNPの簡易検出法

奈良原香織, 平塚真弘, Hamdy Samar Ismail, 岸川幸生, 我妻恭行, 井上智子, 富岡佳久, 水柿道直

日本薬学会年会要旨集　121年会　(3)　40-40　2001/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
STZ誘発糖尿病マウスにおけるTXA2及びTXA2合成系酵素mRNAの変動

塚本宏樹, 菱沼隆則, 富岡佳久, 平塚真弘, 三日市剛, 水柿道直

日本薬学会年会要旨集　121年会　(3)　35-35　2001/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
ddY系マウスにおいて脂肪酸を代謝するチトクロームP450分子種の同定

佐藤益男, 平塚真弘, 富岡佳久, 菱沼隆則, 水柿道直, 永田清, 山添康

薬物動態　13　(Suppl.)　S245-S245　1998/10
Publisher: (一社)日本薬物動態学会
ISSN： 0916-1139
The effects of unsaturated fatty acids, oxidizing agents and Michael reaction acceptors on the induction of N-ethylmaleimide reductase in Escherichia coli: Possible application for drug design of chemoprotectors

K Miura, Y Tomioka, Y Hoshi, H Suzuki, M Yonezawa, T Hishinuma, M Mizugaki

METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY　19　(3)　147-151　1997/04

ISSN： 0379-0355
Effects of haloperidol and cocaine pretreatments on brain distribution and kinetics of [11C]methamphetamine in methamphetamine sensitized dog: application of PET to drug pharmacokinetic study.

NAKAMURA H, HISHINUMA T, TOMIOKA Y, ISHIWATA S, MIZUGAKI M, IDO T, IWATA R, FUNAKI Y, NUMACHI Y

Nucl. Med. Biol.　24　(2)　165-169　1997

DOI： 10.1016/S0969-8051(96)00204-1 　

ISSN： 0969-8051
Phenobarbital molecularly imprinted polymer selectively binds phenobarbital.

Yoshihisa TOMIOKA, Yoshiki KUDO, Tetsuro HAYASHI, Hitoshi NAKAMURA, Masahiro NIIZEKI, Takanori HISHINUMA, Michinao MIZUGAKI

Biol. Pharm. Bull.　20　(4)　397-400　1997
Publisher: The Pharmaceutical Society of Japan
DOI： 10.1248/bpb.20.397 　

ISSN： 0918-6158 1347-5215

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Molecularly imprinted polymer (MIP) was propared against phenobarbital using methacrylic acid as the functional monomer and ethylene glycol dimethacrylate as the cross linking monomer. We analyzed the recognition properties of the phenobarbital MIP. In some organic solvents, imprinted polymer showed selective binding to phenobarbital. Two dissociation constants of binding were calculated by Scatchard plot analyses; K_d values were 1.8, 121.7 μM, and the number of binding sites was 8.3, 92.3 μmol/g MIP in toluene-heptane-acetic acid (25 : 75 : 1, v/v), respectively. The relationship between the binding affinity to phenobarbital MIP and the polarity of the solvent system, as well as the structure of the template molecule is also discussed.
23B-18 Phenobarbital Imprinted Polymer の物理化学的性質について

水柿道直, 林哲郎, 工藤義樹, 菱沼隆則, 富岡佳久

日本病院薬学会年会講演要旨集　5　262-263　1995/06/30
Publisher: 日本医療薬学会
B-15 向精神薬の体内動態と作用発現に関する研究 VII : ポジトロン標識コカインのマウス脳内動態の検討

中村仁, 木村勝彦, 菱沼隆則, 麻生久, 伊藤邦彦, 富岡佳久, 石渡俊二, 盛谷浩史, 伊藤鍛, 水柿道直

日本病院薬学会年会講演要旨集　2　68-69　1992/06/25
Publisher: 日本医療薬学会
Alteration in biodistribution of 11C-methamphetamine and 13C-cocaine

Mizugaki M, Nakamura H, Kimura k, Aso H, Ishii F, Itoh K, Tomioka Y, Itoh Ki, Nishikawa M, Uyama T

CYRIC Ann. Rep. 1991　133-138　1992/01/01
39 向精神薬の体内動態と作用発現に関する研究 V : ポジトロン標識メタンフェタミンの動態と依存症との関連性について

水柿道直, 菱沼隆則, 中村仁, 麻生久, 伊藤邦彦, 富岡佳久

日本病院薬学会年会講演要旨集　1　130-131　1991/06/25
Publisher: 日本医療薬学会
Synthesis of 13C-labeled cocaine and its biodistribution in mice.

Kimura k, Hishinuma T, Aso H, Ishii F, Itoh K, Tomioka Y, Nishikawa M, Uyama T, Nakamura H, Mizugaki

CYRIC Ann. Rep. 1990　93-99　1991/01/01

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Books and Other Publications 9

病気と薬パーフェクトＢＯＯＫ２００９

鈴木直人, 小澤実香, 富岡佳久

南山堂　2009/03/24
わかりやすい薬学生のための病態生理と薬物治療

厚味厳一, 小佐野博史, 田口恭治, 富岡佳久, 平野俊彦

2008/09/11
病気と薬パーフェクトＢＯＯＫ２００８

鈴木直人, 小澤実香, 富岡佳久

南山堂　2008/03/24
シンプル生化学改訂第５版

林典夫, 野治子

2008/02/20
Pharmacotherapy: A pathophysiologic approach

百瀬弥寿徳

ブレーン出版　2007/08/20
環境・健康科学事典

日本薬学会

2005/02/28

ISBN: 4621075365
病院薬局実務体系

宮崎勝巳, 水柿道直, 丹野慶紀, 高杉益充, 大石了三

1998/08/10

ISBN: 4753217183
Biotechnology and Pharmacy

福地坦, 水柿道直

医薬ジャーナル社　1997/11/10

ISBN: 4753216675
医学・生物学のための画像解析ハンドブック実践NIH Image講座

沼原利彦, 小島清嗣

羊土社　1995/02/20

ISBN: 4897066069

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Research Projects 13

Search for molecules that control the CD39-CD73-adenosine cascade and expand into drug discovery

Tomioka Yoshihisa

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2019/04/01 - 2022/03/31

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Enzymatic evaluation methods and enzymatic evaluation methods for compounds that inhibit or increase the enzymatic activity of CD73 or CD39 for the small molecule discovery of novel cancer immunotherapy targeting the PD-1 / PD-L1 independent immunosuppressive pathway. As a result of screening and evaluating 6,080 species of the Tohoku University compound library using the evaluation method using mouse spleen cells, 19 promising seed candidate compounds were obtained. We succeeded in obtaining three compounds selective for CD73 from the enzyme reaction curves of one of the 13 analog compounds.
Investigation of the modified nucleic acid for novel cancer evaluation marker candidates and its diagnostic application.

Tomioka Yoshihisa, NUMASAKI Muneo

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2016/04/01 - 2019/03/31

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Cancer immunotherapy with PD-1 antibody has been applied in clinical settings. Because pathological conditions are differences in each cancer patients, it is expected to develop an evaluation for different immune suppression mechanism such as PD-1 and/or PD-L1. In this study, we focus on modified nucleosides and nucleotides that have long been implicated in cancer pathologies, but whose pharmacokinetics and immune function is still unknown in many ways. The quantitative, qualitative, accurate, and comprehensive methods were developed in this study, We also found that nucleic acids such as methylated adenosine suppress T cell activation, suggesting that modified nucleic acids may be involved in cancer immunosuppression. This result indicates the possibility that cancer immunopathology can be grasped and treated based on a new standard different from the past, and it can be expected to contribute to the further development of cancer treatment.
Elucidation of the mechanism of radioresistance in cancer cells using trans-omics approach and development of clinical biomarkers for radiotherapy.

Kanemitsu Yoshitomi, TOMIOKA Yoshihisa, MATSUMOTO Yotato, TSUKAMOTO Hiroki, FUKUMOTO Manabu, KUWAHARA Yoshikazu

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Young Scientists (B)

Institution: Tohoku University

2016/04/01 - 2018/03/31

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In this study, we aimed to identify the molecules involved in radioresistance of cancer cells and to elucidate its mechanism. Here, we quantitatively compared the proteomes and the metabolomes of clinically relevant radioresistant (CRR) cell lines and their parent strains. In CRR cells, the chaperones and the proteins involved in oxidative stress were higher than control cell lines. Pathways such as amino acid metabolism and fatty acid metabolism were found to be highly enriched in CRR cells. These molecules can be expected as radiation tolerance markers and/or new targets for cancer therapies.
A novel immunotherapy of autoimmune disease by agonistic toll-like receptor 4 antibody

TSUKAMOTO HIROKI, TOMIOKA Yoshihisa

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2014/04/01 - 2017/03/31

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Type 1 diabetes (T1D) is currently an incurable disease as other most autoimmune diseases. The pathology of T1D progresses from a silent prodromal phase to a clinical phase in which insulin-producing pancreatic β cells is destructed by autoreactive T cells. In this study, we demonstrated that an agonistic monoclonal antibody (mAb) to Toll-like receptor 4 (TLR4) prevents from the onset of T1D by prophylactic treatment and also reverses the new-onset of T1D by therapeutic treatment in nonobese diabetic mice. An agonistic TLR4 mAb induces the tolerance in innate immunity via dendritic cells and myeloid-derived suppressor cells, which results in the suppression of autoimmune T cells. In addition, regulatory T cells are also induced by agonistic TLR4 mAb in both periphery and pancreatic islets. These results propose that a tolerance induction through innate immunity by TLR4 mAb may be a novel immunological approach to cure the autoimmune pathology in T1D.
Research of sphingolipids as a novel tumor marker for clinical study

TOMIOKA YOSHIHISA

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2013/04/01 - 2016/03/31

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Using the quantitative method of high sensitivity mass spectrometry for sphingolipid, healthy subjects and blood sphingolipid of each cancer patient was analyzed quantitatively. Especially, it was investigated clinical applicability as a novel tumor marker of SlP. Plasma S1P concentrations were 410±67 nM, 620±129 nM, 484±151 nM, and 491±106 nM in healthy, esophageal cancer, stomach cancer, sarcoma, respectively. Esophageal cancer patient plasma S1P concentration was for the first time revealed that it is significantly higher compared to the healthy subjects. Using metabolome analysis profiling for cancer disease analysis as some new biomarker candidates, in particular, I found the possibility of cystine.
Effect of docosenoic acid and icosenoic acid on the type 2 diabetic mellitus and atopic dermatitis.

Nishikawa Masazumi, TOMIOKA Yoshihisa

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (C)

Institution: Miyagi University

2012/04/01 - 2016/03/31

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We investigated the effect of docosenoic acid and icosenoic acid, the abundant monounsaturated fatty acids in the saury oil, on the type-2 diabetic mellitus and atopic dermatitis. Supplementation with docosenoic acid and icosenoic acid had reduced Atopic dermatitis like skin lesions and the frequency of scratching episodes in a time-dependent manner on atopic NC/Nga mice. Furthermore, docosenoic acid and icosenoic acid had reduced weight and insulin sensitivity had improved on the type-2 diabetic KK-Ay mice. From these results, it appears that docosenoic acid and icosenoic acid can contribute to the prevention of a lifestyle-related disease and the allergic disease.
Construction of a practical education system for pharmacy students, pharmacists, and teachers with case follow-up

MURAI YURIKO, MANO Nariyasu, TOMIOKA Yoshihisa

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2011 - 2013

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Objective of this study is to establish the sustainable system of pharmacy education to cultivate human resources who contribute to healthcare with pharmaceutical sciences. We conducted on-site training in hospital with 6 times during the 3-year study period. Weekly case conferences were held in the training for 11 weeks by one term. Advising pharmacists, teachers, and fifth-year pharmacy students who were on the training attended the conferences. Basic points to discuss about pharmacotherapy or pharmaceutical care were demonstrated and presented to the students in the guidance of case conferences. According to the points, students had group discussions and presentations in case conferences about their patients. Students' levels of understanding or satisfaction improved comparing with that before. Through continuous follow-up of patients, discussion, and information sharing, it considered that participants including pharmacists and teachers gained clinical competency.
Analysis of functional significance of a newly discovered brain-specific transporter

NAKAJIMA Akira, MANO Nariyasu, TOMIOKA Yoshihisa, YAMAGUCHI Hiroaki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (B)

2008 - 2010

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We have focused on a newly discovered human brain-specific transporter SLC10A4, which is specifically localized in the substantia nigra. Over-expression cell of human SLC10A4 was successfully generated using human HepG2 cell. A low SLC10A4-mediated uptake of bile acids, such as chenodeoxycholic acid and ursodeoxycholic acid, was observed in the transformant. The expression of SLC10A4 was investigated in various cultured cells using immunoblot analysis. Finally, human brain-derived TE671(medulloblastoma) cells were found that they had a stable expression of SLC10A4. It was noteworthy finding that the uptake of taurocholic acid was induced by thrombin pretreatment in the TE671 cells and the Km value was higher than that of known sodium taurocholate co-transporting polypeptides, such as ASBT and NTCP. We considered that SLC10A4 was special brain transporter, could be activated and responsible for the uptake of bile acids when blood clotting was occurred following blood vessel damage or tissue injury.
Basic Study for the Design and the Preparation of the Artificial Protein Modules and its Pharmaceutical Applications

TOMIOKA Yoshihisa, OZAWA Mika, SUZUKI Naoto, HISHIMURA Takanori

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (C)

Institution: Josai International University

2005 - 2006

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In order to investigate and/or determine the structure of glycyrrhetic acid (GA) to contribute the binding affinity and specificity against the antibodies, the mouse anti-GA monoclonal antibody (AGA-1) was carefully investigated the binding to the GA-derived compounds, which were 17 compounds tested, with the inhibition ELISA. AGA-1 binding was inhibited by the 16 compounds investigated, except bile acid. We found that the A-ring, the C-3 hydroxyl group, and the C-30 carbonic group for the E-ring, oleanane structure and its C-11 carbonic group were important for the recognition of the AGA-1. We prepared the recombinant Fab fragment antibodies which were substituted the each amino acid in the CDR-H3 with alanine, and investigated the binding activities against the GA-BSA with ELISA. It suggested that the amino acid-side chains for the root region of the CDR-H3 was contributed to the specific binding. In order to investigate the reactivity of the AGA-1 and each rFab, GA was fixed on the sensor chip CM5 for BIACORE and tested. The kinetic parameters were calculated. The parameters kon (E4 /M/s), koff (E4 /M/s), and KD (E-9 M) for AGA-1 were 37.4 31.6, and 3.2, respectively. However, the parameters for the rFab were Y99A (0.9, 0.2, 20.8), Y100bA (36.4, 2.3, 6.2), D101A (16.5, 3.7, 25.1), W95A (5.2, 5.1, 98.4), respectively.
Basic Study for the Design and the Preparation of the Artificial Drug Binding Protein Modules and its Pharmaceutical Applications.

TOMIOKA Yoshihisa, GOTO Junichi, HISHINUMA Takanori, OZAWA Mika

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (C)

Institution: Josai International University

2003 - 2004

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In order to investigate the amino acid residues in apo-NCS involving the binding with the NCS-chr, the amino acid-substituted apo-NCS mutants (S98C, S98G, S98T and S98A) were prepared. The binding of the non-natural chromophore, EtdBr, with the each mutated apo-NCS was evaluated by the monitoring for the total fluorescence intensity and fluorescence polarization. The S98G mutant had the best binding property compared with another apo-NCS. The result suggested that the strategy of the substitution for the proper amino acid residues in apo-NCS could be expected to create supernatural apo-NCS. The randomized libraries were successfully prepared using the megaprimer PCR mutagenesis, the overlap extension PCR mutagenesis with dam methylase / DpnI digestion method. The mutated amino acids were total 14, and their sites were region A (49-52, PADF), region B (76-80, FLFDG), and region C (94-98, QVGLS), which are involving the binding with NCS-chr. The randomized library was successfully inserted into the vector DNA for the phage display, and performed a screening using bio-panning method against the glycyrrhetic acid conjugated bovine serum albumin (GA-BSA), and then isolated the clones which had a specific binding property to the GA-BSA. Hereafter, the detail structure analysis will be investigated for the isolated clones.
Development of diagnosis of Atopic Dermatitis by simple and high-sensitive determination method of LTE4

HISHINUMA Takanori, AIBA Setsuya, TOMIOKA Yoshihisa

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (C)

Institution: TOHOKU UNIVERSITY

2002 - 2003

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Liquid chromatography/tandem mass spectrometric method (LC/MS/MS) was developed for the quantitation of leukotriene E4(LTE4) in human urine. After addition of deuterium labeled internal standard to urine, these subjects were extracted by solid-phase extraction using Empore C18 disk cartridge. The reconstituted extracts were analysed by LC/MS/MS in the selected reaction monitoring (SRM) mode monitoring. Leukotrienes (LTs) are inflammatory mediators derived from arachidonic acid by the action of 5-lipoxygenase. The cysteinyl LTs (LTC4, LTD4 and LTE4) are inflammatory mediators and are known to play a part in the pathogenesis of inflammatory diseases. They increase vascular permeability and dilate skin blood vessels. Thus, a potential role for enhanced LT production in the pathogenesis of AD has been suggested. Urinary LTE4 levels are a useful index of whole-body cysteinyl LT production in vivo because LTE4 is a stable urinary metabolite of LTC4 and LTD4. Atopic dermatitis (AD) is a chronic inflammatory skin disease frequently seen in patients with a personal or family history of respiratory allergy. Many observations have indicated that IgE-mediated mechanisms play a part in the pathogenesis of AD. I used LC/MS-MS to determine urinary LTE4 levels in patients with AD and healthy volunteers, and examined the relationship between urinary LTE4 and total serum IgE levels. I clarified theincreased LTE4 excretion in patients with AD compared with healthy volunteers, and a significant correlation between urinary LTE4 and total serum IgE levels in patients with AD. The present findings suggest that cysteinyl LTs play a crucial part in the pathogenesis of AD. Beneficial effects of 5-lipoxygenase inhibitors and receptor antagonists may be expected in the treatment of AD. Moreover, the diagnosis of AD is primarily based on skin tests and measurements of total IgE and specific IgE in serum. Measurement of urinary LTE4, which is simple and non-invasive, may be useful in evaluating the serum IgE level and assessing the pathological symptoms in AD. Furthermore, to compare the relation to AD with LTE4, I developed microdetermination method of 11-dehydro thromboxane B2(11-dehydro TXB2, a urinary metabolite of thromboxane A2).
A Study on Designed Hapten Aimed at Anti-ciguatoxin Monoclonal Antibody

HIRAMA Masahiro, OGURI Hiroki, TOMIOKA Yoshihisa, MIZUGAKI Michinao

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (B).

Institution: Tohoku University

1998 - 2000

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The ABC-ring fragment of ciguatoxin was synthesized as a C2 epimeric mixture (1 : 1 ). The mixture, which was designed as a possible hapten for preparing an anti-ciguatoxin monoclonal antibody, was conjugated with a carrier protein (KLH) and then used for immunization of mice. The three monoclonal antibodies (mAbs) obtained have shown an appreciable reactivity to the hapten. Each mAb discriminated configuration of the C2 hydroxy group of the ABC-ring fragment. The mAb which showed reactivity to the 2S-fragment was cross-reacted with ciguatoxin. Furthermore, new and efficient synthetic methods utilizing olefin methathesis were developed and several designed haptens have been prepared and conjugated with KLH and BSA, which have been used for immunization of mice.
抗生理活性物質抗体の構造解析と機能性ペプチド分子創生への応用

富岡佳久

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 奨励研究(A)

Institution: 東北大学

1998 - 1999

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抗生理活性物資抗体(抗グリチルレチン酸抗体、抗シガトキシン抗体)産生ハイブリドーマ細胞から抗体遺伝子をPCR法を用いてクローニングし、反応特異性に密接な可変部領域の塩基配列を決定し、それらの予測アミノ酸配列について遺伝子バンクに登録されている抗体と相同性について解析した。CDR1およびCDR2領域に関して、それぞれ高い相同性が認められたが、CDR3領域の配列に関して相同性の高い配列は認められなかった。これより、CDR3領域が特に抗体と抗原との反応特異性に寄与していることが示唆された。すなわち抗シガトキシン抗体に関して、シガトキシン1B(CTX1B)のABC環部を有機化学的に合成し、KLHとのコンジュゲートとして免疫、マウスモノクローナルを得た。反応特性性に関する検討から、CTX1Bの2位水酸基の立体が2R体と反応する6H7抗体と天然型2S体と反応する6F12抗体及び4H2抗体が得られていた。遺伝子解析から得られた各抗体の予測アミノ酸配列の比較により、6F12と4H2の重鎖領域配列の相同性が高く、可変領域内125アミノ酸残基中115残基(92%)が一致した。そこで、現在pComb3をベクターとしてCDR3領域をランダム化したファージディスプレイFab抗体ライブラリーを作製し、2S-ABC環ー牛血清アルブミン(BSA)コンジュゲートを用いてパンニングを行い、得られたファージクローンの解析を継続している。今後は、CDR1及びCDR2をランダム化した抗体ライブラリーを作製し、ハイブリドーマ法を代替するモノクローナル抗体作製法開発に応用する。

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2009/11/28 -

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日本薬学会東北支部主催医療薬学領域セミナーでの座長
講師

2009/11/21 -

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東北がんプロフェッショナル養成事業における講師
講演

2009/11/14 -

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日本医療薬学会公開シンポジウムにおける特別講演
講師

2009/10/22 -

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福島県立磐城高校における出前授業