Faculty Profiles - TSUKAHARA Hirokazu

MISC - TSUKAHARA Hirokazu

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早産児の慢性肺疾患における酸化ストレスの病態学的意義についての検討: CO-HbとMet-Hbを指標として

徳力周子, 塚原宏一, 巨田尚子, 田村知史, 小倉一将, 川谷正男, 畑郁江, 眞弓光文

小児科臨床 62 ( 5 ) 925 - 930 2009

アルギニン代謝関連分子（NO，ADMA）による生体機能修飾についての統合的研究

塚原宏一

平成19～20年度科学研究費補助金（基盤研究C）研究成果報告書 2009

超早産児のナトリウム補充に関する検討: 晩期循環不全発症予防における電解質管理の重要性

徳力周子, 巨田尚子, 古畑律代, 田村知史, 川谷正男, 畑郁江, 塚原宏一, 眞弓光文

発達腎研究会誌 17 ( 1 ) 7 - 12 2009

小児疾患診療のための病態生理2 - II. 新生児疾患. 21. 新生児代謝性骨疾患

塚原宏一, 巨田尚子, 徳力周子

小児内科 184 - 189 2009

厚生労働科学研究費補助金（新興・再興感染症研究事業）「インフルエンザ脳症の発症因子の解明とそれに基づく発症前診断方法の確立に関する研究」班（主任研究者森島恒雄）. インフルエンザ脳症ガイドライン（改訂版）

森島恒雄, 岡部信彦, 中村祐輔, 河岡義裕, 山口清次, 水口雅, 市山高志, 長谷川秀樹, 奥村彰久, 伊藤嘉規, 河島尚志, 新矢恭子, 塚原宏一, 中野貴司, 塩見正司, 鍵本聖一, 布井博幸, 和田智顕, 植田育也, 山内秀雄, 栗原まな, 宮崎千明, 山田至康, 坂下裕子, 岩田力, 大平雅之, 阪井裕一, 中村通子, 宮澤会美香, 吉川秀人

小児科臨床 62 ( 11 ) 2483 - 2528 2009

周産期におけるMycoplasma hominis, Ureaplasma urealyticum感染の早期スクリーニング法と超早産児の気管支肺異形成発症予防策の確立

徳力周子, 塚原宏一, 西島浩二

トランスレーションリサーチ推進センター 2008年度活動報告書 7 - 8 2009

広汎性発達障害における酸化ストレスの関与に関する研究

川谷正男, 塚原宏一

トランスレーションリサーチ推進センター 2008年度活動報告書 2009

窒素（Ｎ）と酸素（Ｏ）の化学・生物学

塚原宏一

日本臨床高気圧酸素・潜水医学会雑誌 2009

小児科診療に強くなる！- 知ってほしい診断のポイントとコツ. ありふれた症状・症候 - プライマリーケア

塚原宏一

内科 103 ( 1 ) 160 - 163 2009

小児科診療に強くなる！- 知ってほしい診断のポイントとコツ. 連載にあたって

塚原宏一

内科 103 ( 1 ) 159 2009

Fluctuation of lipoprotein metabolism linked with bile acid-activated liver nuclear receptors in Alagille syndrome

Hironori Nagasaka, Takashi Miida, Ken-ichi Hirano, Akemi Ota, Kei Murayama, Tohru Yorifuji, Kunihiko Kobayashi, Tornommi Takatani, Hirokazu Tsukahara, Shu-Ping Hui, Masaki Takayanagi, Hitoshi Chiba

ATHEROSCLEROSIS 198 ( 2 ) 434 - 440 2008.6

Language：English Publisher：ELSEVIER IRELAND LTD

Alagille syndrome (AGS) is a rare hereditary disorder exhibiting fluctuating cholestasis and dyslipidemia. Farnesoid X receptor (FXR) and liver X receptor (LXR) are hepatic nuclear receptors that regulate bile acid and lipoprotein metabolism. To investigate whether cholestasis is related to dyslipidemia and hepatic nuclear receptor expression in AGS patients, we determined the blood levels of total bile acid (TBA) and lipoprotein parameters, and examined hepatic nuclear receptor expression in three AGS children and their three incomplete AGS parents repeatedly over several years. In the AGS children, TBA level showed significant positive correlations with low-density lipoprotein-cholesterol, apolipoprotein E (apoE)-rich high-density lipoprotein-cholesterol (HDL-C), apoA-I, apoE, and cholesteryl ester transfer protein (CETP) concentrations, but negative correlation with apoE-poor HDL-C concentration. Western blot analysis of liver biopsy specimens revealed that FXR and LXR expression increased in parallel with TBA level. CETP- and ATP-binding cassette transporter A1 expression also increased with TBA level, while scavenger receptor class B type-I expression showed the opposite response. However, apoA-I expression was similar to the control level at any TBA level. In the incomplete AGS parents, TBA and lipoprotein parameters showed little fluctuation. In summary, cholestasis is closely related to dyslipidemia and hepatic nuclear receptor expression in AGS patients. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.atheroscierosis.2008.02.020

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Reduced apolipoprotein E-rich high-density lipoprotein level at birth is restored to the normal range in patients with familial Hypercholesterolemia in the first year of life

Hironori Nagasaka, Takashi Miida, Kenichi Hirano, Akemi Ota, Tohru Yorifuji, Tomozumi Takatani, Hirokazu Tsukahara, Masaki Takayanagi, Shu-Ping Hui, Kunihiko Kobayashi, Hitoshi Chiba

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 93 ( 3 ) 779 - 783 2008.3

Language：English Publisher：ENDOCRINE SOC

Background: High-density lipoprotein (HDL) consists of apolipoprotein E (apoE)-rich and apoE-poor HDL particles. ApoE-rich HDL level is high at birth but decreases after birth with reciprocal elevation in low-density lipoprotein (LDL)-cholesterol.
Objectives: The objective of the study was to clarify whether apoE-rich HDL decreases after birth in children with familial hypercholesterolemia (FH), a disorder caused by impaired LDL clearance.
Methods: We measured apoE-rich HDL-cholesterol and LDL-cholesterol during the first year of life in 10 FH children (one homozygote and nine heterozygotes), 12 non-FH siblings, and 75 healthy controls.
Results: At birth, apoE-rich HDL-cholesterol was undetectable in a homozygous FH child and lower in heterozygous FH children than non-FH siblings and controls ( 4 +/- 2 vs. 12 +/- 4 and 11 +/- 4 mg/dl, P < 0.001). At 3-4 months, apoE-rich HDL-cholesterol increased in homozygous and heterozygous FH children and decreased in non-FH siblings and controls. At 12 months, apoE-rich HDL-cholesterol levels were similar among these four groups (6-7 mg/dl). In contrast, LDL-cholesterol concentration was always twice as high in heterozygous FH children as non-FH siblings and controls ( at birth, 50 +/- 15 vs. 25 +/- 7 and 25 +/- 5 mg/dl, P < 0.001; at 3 - 4 months of age, 159 +/- 29 vs. 71 similar to 16 and 73 +/- 15 mg/dl, P < 0.001; at 12 months of age, 156 +/- 29 vs. 75 +/- 18 and 76 +/- 17 mg/dl, P < 0.001).
Conclusion: ApoE- rich HDL level is low at birth in FH children and increases to the normal level in the first year of life, opposite to the change in normal children.

DOI： 10.1210/jc.2007-1621

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Determination of asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, in umbilical blood

Hirokazu Tsukahara, Naoko Ohta, Shuko Tokuriki, Koji Nishijima, Fumikazu Kotsuji, Hisako Kawakami, Norihito Ohta, Kyouichi Sekine, Hironori Nagasaka, Mitsimi Mayumi

METABOLISM-CLINICAL AND EXPERIMENTAL 57 ( 2 ) 215 - 220 2008.2

Language：English Publisher：W B SAUNDERS CO-ELSEVIER INC

Endothelial cells produce nitric oxide (NO), a potent vasodilator. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase. Little is known about the potential physiological roles of ADMA in a perinatal setting. This study measures concentrations of ADMA in umbilical blood using enzyme-linked immunosorbent assay and those of NO as nitrite/nitrate (NOx(-)) using the Griess assay. Their relationship to the degree of prematurity and maternal clinical condition is examined. Results show that ADMA concentrations in umbilical blood from control newborns were about twice as high as those of lactating women, healthy children, and healthy adults. Umbilical blood NOx(-) concentrations from control newborns were about half of those of lactating women, healthy children, and healthy adults. Consequently, the levels of ADMA relative to NOx(-) were about 4-fold higher in umbilical blood from control newborns than in blood from lactating women, healthy children, and healthy adults. Furthermore, the umbilical blood ADMA concentrations and the ratios of ADMA to NOx(-) in newborns were higher according to their birth prematurity and lower birth weight. The umbilical ADMA concentrations were independent of the delivery mode and maternal preeclampsia. We infer that the high ADMA levels play physiological roles in maintaining vascular tone and blood redistribution to vital organs during birth, thereby favoring the circulatory transition from fetal to neonatal life. (C) 2008 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.metabol.2007.09.003

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High levels of growth factors in human breast milk

Ritsuyo Kobata, Hirokazu Tsukahara, Yusei Ohshima, Naoko Ohta, Shuko Tokuriki, Satoshi Tamura, Mitsufumi Mayumi

EARLY HUMAN DEVELOPMENT 84 ( 1 ) 67 - 69 2008.1

Language：English Publisher：ELSEVIER IRELAND LTD

We found very high concentrations of vascular endothelial growth factor, hepatic growth factor, and epidermal growth factor in early breast milk samples obtained from healthy mothers of term infants. This is the first report of simultaneous measurements of three major gastrointestinal trophic substances in human milk. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.earlhumdev.2007.07.005

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小児医療における腎機能評価

塚原宏一

臨床化学 37 ( 1 ) 35 - 44 2008