Faculty Profiles - TSUKAHARA Hirokazu

MISC - TSUKAHARA Hirokazu

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環境ホルモンの影響に関する検討

眞弓光文, 大嶋勇成, 塚原宏一

独立行政法人環境再生保全機構公害健康被害補償予防協会委託業務報告書：気管支ぜん息等の発症・増悪リスクとしての環境要因の寄与の程度に関する研究報告書2004年度工藤翔二研究班報告書 61 - 71 2005

病的新生児、特に超低出生体重児の『後遺症なき生存』を目指して: 当院未熟児診療部における『レドックス（抗酸化ストレス）療法』の推進とその評価

塚原宏一, 大嶋勇成

福井大学重点研究成果報告書 80 - 81 2005

各種疾患におけるレドックス制御とその異常

塚原宏一, 眞弓光文

アレルギー・免疫 12 ( 5 ) 733 - 737 2005

腎尿路異常の早期発見のための3歳児検尿の施行法および費用対便益の検討

平岡政弘, 塚原宏一

平成16年度科学研究費補助金基盤研究C(2)実績報告書 2005

小児の食と栄養Q&A<アレルギー>ペプチド分解乳で牛乳アレルギーの予防ができるのか?母乳はアトピー性皮膚炎に良くないのか?

塚原宏一, 大嶋勇成

小児内科 37 ( 5 ) 2005

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion

H Tada, J Takanashi, AJ Barkovich, H Oba, M Maeda, H Tsukahara, M Suzuki, T Yamamoto, T Shimono, T Ichiyama, T Taoka, O Sohma, H Yoshikawa, Y Kohno

NEUROLOGY 63 ( 10 ) 1854 - 1858 2004.11

Language：English Publisher：LIPPINCOTT WILLIAMS & WILKINS

Objective: To clarify whether patients with clinical diagnoses of encephalitis/encephalopathy with a reversible lesion in the splenium of the corpus callosum (SCC) share common clinical features. Methods: Possible encephalitis/encephalopathy patients with a reversible isolated SCC lesion on MRI were collected retrospectively. Their clinical, laboratory, and radiologic data were reviewed. Results: Fifteen encephalitis/encephalopathy patients with a reversible isolated SCC lesion were identified among 22 patients referred for this study. All 15 patients had relatively mild clinical courses. Twelve of the 15 patients had disorders of consciousness. Eight patients had seizures, and three of them received antiepileptic drugs. All 15 patients clinically recovered completely within 1 month ( 8 patients within a week) after the onset of neurologic symptoms. The SCC lesion was ovoid in six patients; it extended irregularly from the center to the lateral portion of SCC in the other eight patients. Homogeneously reduced diffusion was seen in all seven patients who underwent diffusion-weighted imaging. There was no enhancement in the five patients so examined. The SCC lesion had completely disappeared in all patients at follow-up MRI exams between 3 days and 2 months after the initial MRI ( within 1 week in eight patients). Conclusion: The clinical features among the affected patients were nearly identical, consisting of relatively mild CNS manifestations and complete recovery within 1 month.

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Neonatal bone abnormalities attributable to maternal administration of magnesium sulphate

H Tsukahara, R Kobata, S Tamura, M Mayumi

PEDIATRIC RADIOLOGY 34 ( 8 ) 673 - 674 2004.8

Effects of antioxidant and nitric oxide on chemokine production in TNF-alpha-stimulated human dermal microvascular endothelial cells

H Tsukahara, MZ Jiang, Y Ohshima, Y Todoroki, S Sato, S Tamura, M Hiraoka, M Maeda, M Mayumi

NITRIC OXIDE-BIOLOGY AND CHEMISTRY 11 ( 1 ) 118 - 118 2004.8

Impaired homeostasis of oxygen/nitrogen radicals in childhood atopic dermatitis

H Tsukahara, S Ito, Y Ohshima, N Omata, M Yasutomi, M Hiraoka, M Nambu, Y Deguchi, M Mayumi

NITRIC OXIDE-BIOLOGY AND CHEMISTRY 11 ( 1 ) 118 - 118 2004.8

Concentrations of pentosidine, an advanced glycation end-product, in umbilical cord blood

H Tsukahara, N Ohta, S Sato, M Hiraoka, K Shukunami, M Uchiyama, H Kawakami, K Sekine, M Mayumi

FREE RADICAL RESEARCH 38 ( 7 ) 691 - 695 2004.7

Language：English Publisher：TAYLOR & FRANCIS LTD

Advanced glycation end-products (AGEs) are formed over several weeks to months by non-enzymatic glycation and oxidation ("glycoxidation") reactions between carbohydrate-derived carbonyl groups and protein amino groups, known as the Maillard reaction. Pentosidine is one of the best-characterized AGEs and is accepted as a satisfactory marker for glycoxidation in vivo . The present study was intended to measure pentosidine concentrations in umbilical cord blood from newborns with various gestational ages using our recently established high-performance liquid chromatography method [Tsukahara, H. et al. (2003) Pediatr. Res. 54 , 419-424]. Our study demonstrates, for the first time, that pentosidine is detected in most of the umbilical blood samples. This study also shows that the umbilical blood concentrations of pentosidine are considerably lower than normal adult values, but that they increase with gestation progression and fetal growth. Umbilical pentosidine concentrations were significantly elevated in newborns of mothers with preeclampsia compared to those of mothers without preeclampsia. We conclude that accumulation of AGEs and oxidative stress occurs in fetal tissues and organs in utero at the early stage of human life and that their accumulation is augmented in the maternal preeclampsic condition.

DOI： 10.1080/1071576042000220256

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Oxidative stress in neonates: Evaluation using specific biomarkers

H Tsukahara, MZ Jiang, N Ohta, S Sato, S Tamura, M Hiraoka, M Maeda, M Mayumi

LIFE SCIENCES 75 ( 8 ) 933 - 938 2004.7

Language：English Publisher：PERGAMON-ELSEVIER SCIENCE LTD

Increased oxidative stress has been implicated in pathogenesis of serious diseases in neonates. We measured urinary levels of 8-hydroxy-2'-deoxyguanosine (a marker of oxidative DNA damage), acroleinlysine adduct (a marker of lipid peroxidation and oxidative protein damage), and nitrite/nitrate (a marker of endogenous nitric oxide formation) in one-month-old neonates to examine the status of oxidative stress and its relationship to the degree of prematurity and clinical condition in neonates. Study subjects comprised three groups: healthy term neonates, clinically stable preterm neonates requiring no supplemental oxygen, and clinically sick preterm neonates requiring supplemental oxygen and ventilator support. Urinary levels of 8-hydroxy-2'-deoxyguanosine and acrolein-lysine adduct were significantly higher in sick preterm neonates than those of stable preterm and healthy term neonates. In the sick preterm group, neonates developing active retinopathy showed significantly higher levels of acrolein-lysine adduct than the other neonates without retinopathy. There were no significant differences in both urinary markers of oxidative stress between stable preterm and healthy term neonates. The urinary nitrite/nitrate levels were not significantly different among the three groups, suggesting no difference in endogenous nitric oxide fort-nation. Collectively, these results provide evidence of augmentation of oxidative damage to DNA, lipids and proteins, especially in clinically sick preterm neonates. (C) 2004 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.lfs.2004.01.025

Effects of antioxidants and nitric oxide on TNF-alpha-induced adhesion molecule expression and NF-kappa B activation in human dermal microvascular endothelial cells

MZ Jiang, H Tsukahara, Y Ohshima, Y Todoroki, M Hiraoka, M Maeda, M Mayumi

LIFE SCIENCES 75 ( 10 ) 1159 - 1170 2004.7

Language：English Publisher：PERGAMON-ELSEVIER SCIENCE LTD

Cell adhesion molecules expressed on endothelial cells in inflamed skin appear to be controlled by the actions of cytokines and reactive oxygen species. However, molecular mechanisms of the expression of adhesion molecules during skin inflammation are currently not well understood. To evaluate the role of antioxidants and nitric oxide in modulating inflammatory processes in the skin, we examined the effects of pyrrolidine dithiocarbamate (PDTC, 0.1 mM) and spermine NONOate (Sper-NO, 1 mM) on adhesion molecule expression and nuclear factor kappa B (NF-KB) activation induced by TNF-alpha (10 ng/ml) in cultured human dermal microvascular endothelial cells (HDMEC). Treatment of cells with TNF-alpha for 4 h significantly induced the surface expression of E-selectin and intercellular adhesion molecule-1 (ICAM-1). Treatment with TNF-alpha for 8 h significantly induced the surface expression of E-selectin, ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1). The up-regulation of these adhesion molecules was suppressed significantly by pretreatment with PDTC or Sper-NO for 1 h. The mRNA expression of E-selectin, ICAM-1 and VCAM-1, and activation of NF-kappaB induced by TNF-alpha for 2 h were significantly decreased by the above two pretreatments. N-acetylcysteine (10 mM) and S-nitroso-N-acetylpenicillamine (1 mM) had no significant inhibitory effects on the cell surface and mRNA expression of these adhesion molecules stimulated by TNF-. These findings indicate that both cell surface and mRNA expression of adhesion molecules in HDMEC induced by TNF-alpha are inhibited significantly by pretreatment with PDTC or Sper-NO, possibly in part through blocking the activation of NF-KB. These results suggest a potential therapeutic approach using antioxidant agents or nitric oxide pathway modulators in the treatment of inflammatory skin diseases. (C) 2004 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.lfs.2004.01.031

Nitric oxide metabolites and adrenomedullin in human breast milk

N Ohta, H Tsukahara, Y Ohshima, M Nishii, Y Ogawa, K Sekine, K Kasuga, M Mayumi

EARLY HUMAN DEVELOPMENT 78 ( 1 ) 61 - 65 2004.6

Language：English Publisher：ELSEVIER IRELAND LTD

We found high concentrations of nitrite/nitrate (166-1460 mumol/l) in 43 milk samples obtained from 32 women during postpartum days 1-8, which indicates enhanced mammary nitric oxide (NO) secretion. We detected adrenomedullin (AM) (2.7-20.7 pmol/l) only in 9 of the 43 samples using highly specific immunoradiometric assay. It is uncertain whether the entire adrenomedullin is actively secreted in human milk. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.earlhumdev.2004.04.002

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Many confounding factors influencing urinary beta(2)-microglobulin excretion in premature newborns

H Tsukahara, M Hiraoka, M Mayumi

JOURNAL OF PEDIATRICS 144 ( 6 ) 835 - 836 2004.6

Effects of antioxidant and nitric oxide on chemokine production in TNF-alpha-stimulated human dermal microvascular endothelial cells

MZ Jiang, H Tsukahara, Y Ohshima, S Sato, Y Todoroki, M Hiraoka, M Mayumi

FREE RADICAL RESEARCH 38 ( 5 ) 473 - 480 2004.5

Language：English Publisher：TAYLOR & FRANCIS LTD

Chemokines have been implicated convincingly in the driving of leukocyte emigration in different inflammatory reactions. Multiple signaling mechanisms are reported to be involved in intracellular activation of chemokine expression in vascular endothelial cells by various stimuli. Nevertheless, redox-regulated mechanisms of chemokine expression in human dermal microvascular endothelial cells (HDMEC) remain unclear. This study examined the effects of pyrrolidine dithiocarbamate (PDTC, 0.1 mM) and spermine NONOate (Sper-NO, 1 mM) on the secretion and gene expression of chemokines, interleukin (IL)-8, monocyte chemotactic protein (MCP)-1, regulated upon activation normal T cell expressed and secreted (RANTES), and eotaxin. This study also addresses PDTC and Sper-NO effects on activation of nuclear factor kappa B (NF-kappaB) induced by TNF-alpha (10 ng/ml). Treatment with TNF-alpha for 8 h significantly increased secretion of IL-8, MCP-1, and RANTES, but not of eotaxin, in cultured HDMEC. Up-regulation of these chemokines was suppressed significantly by pretreatment with PDTC or Sper-NO for 1 h, but not by 1 mM 8-bromo-cyclic GMP. The mRNA accumulation of IL-8, MCP-1, RANTES, and eotaxin, and activation of NF-kappaB were induced by TNF-alpha for 2 h; all were suppressed significantly by the above two pretreatments. These findings indicate that both secretion and mRNA accumulation of IL-8, MCP-1, and RANTES in HDMEC induced by TNF-alpha are inhibited significantly by pretreatment with PDTC or Sper-NO, possibly via blocking redox-regulated NF-kappaB activation. These results suggest that restoration of the redox balance using antioxidant agents or nitric oxide pathway modulators may offer new opportunities for therapeutic interventions in inflammatory skin diseases.

DOI： 10.1080/1071576042000209826

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Brain stem hypertensive encephalopathy evaluated by line scan diffusion-weighted imaging

M Nagata, M Maeda, H Tsukahara, SE Maier, K Takeda

AMERICAN JOURNAL OF NEURORADIOLOGY 25 ( 5 ) 803 - 806 2004.5

Language：English Publisher：AMER SOC NEURORADIOLOGY

Hypertensive encephalopathy rarely presents with predominant involvement of the brain stem and relative sparing of the supratentorial regions. We describe the MR imaging features in a patient with reversible brain stem hypertensive encephalopathy. Extensive hyperintensity was predominantly seen in brain stem regions on fluid-attenuated inversion-recovery and T2-weighted images. These lesions showed an increased apparent diffusion coefficient with the use of line scan diffusion-weighted imaging. The clinical findings and MR imaging abnormalities resolved with control of hypertension.

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Endothelial dysfunction in Kawasaki disease: focus on nitric oxide

S Sato, H Tsukahara, N Ohta, Y Todoroki, K Nishida, M Mayumi

PEDIATRICS INTERNATIONAL 46 ( 1 ) 114 - 114 2004.2

N2O anesthesia may exacerbate hyperhomocysteinemia and endothelial dysfunction in patients with renal impairment

H Tsukahara, Y Todoroki, M Hiraoka, M Mayumi

KIDNEY INTERNATIONAL 65 ( 1 ) 338 - 338 2004.1

Diffuse leptomeningeal hyperintensity on fluid-attenuated inversion recovery MR images in neurocutaneous melanosis

M Hayashi, M Maeda, T Maji, T Matsubara, H Tsukahara, K Takeda

AMERICAN JOURNAL OF NEURORADIOLOGY 25 ( 1 ) 138 - 141 2004.1

Language：English Publisher：AMER SOC NEURORADIOLOGY

Neurocutaneous melanosis (NCM) is a rare neuroectodermal dysplasia characterized by large or multiple cutaneous congenital pigmented nevi and benign or malignant melanocytic tumors of the leptomeninges. Although the MR manifestations of this disease have been reported in a small series of cases, the usefulness of fluid-attenuated inversion recovery (FLAIR) MR findings has not been documented. We present a case of NCM that showed diffuse leptomeningeal hyperintensity on FLAIR images. This FLAIR finding may be a clue to the detection of leptomeningeal abnormalities in NCM.

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MR signal changes in a child with cat scratch disease encephalopathy and status epilepticus

K Ogura, Y Hara, H Tsukahara, M Maeda, M Tsukahara, M Mayumi

EUROPEAN NEUROLOGY 51 ( 2 ) 109 - 110 2004

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