Faculty Profiles - TSUKAHARA Hirokazu

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新生児: 体液・電解質異常

塚原宏一

小児科診療（増刊号: 小児の治療指針） 69 861 - 867 2006

乳幼児の尿路感染症の診断のポイント

塚原宏一

小児科 46 ( 13 ) 2133 - 2142 2005.12

Transient focal lesions in the splenium of the corpus callosum with restricted diffusion: An enigma

M Maeda, H Tsukahara

CURRENT MEDICAL IMAGING REVIEWS 1 ( 3 ) 313 - 318 2005.11

Language：English Publishing type：Book review, literature introduction, etc. Publisher：BENTHAM SCIENCE PUBL LTD

Small transient lesions in the central part of the splenium of the corpus callosum (SCC) have been reported in MR examinations, particularly in patients with encephalitis or encephalopathy, and in patients with or without epilepsy who are receiving antiepileptic drugs. The MR findings are characteristic: an ovoid T2-high signal lesion in the SCC, no enhancement after contrast agent, restricted diffusion shown by diffusion MR imaging, and complete disappearance on follow-up MR examinations. Most noteworthy is that these lesions have restricted diffusion but are reversible, which is distinct from infarction lesions seen in energy failure. The exact mechanism of these transient lesions remains uncertain and enigmatic. We review previously reported patients to show these unique MR findings and describe possible pathogenesis of particular SCC lesions.

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Quantitation of glutathione S transferase-pi in the urine of preterm neonates

H Tsukahara, M Toyo-Oka, Y Kanaya, K Ogura, M Kawatani, A Hata, M Hiraoka, M Mayumi

PEDIATRICS INTERNATIONAL 47 ( 5 ) 528 - 531 2005.10

Language：English Publisher：WILEY-BLACKWELL PUBLISHING, INC

Background: Glutathione S transferases (GSTs) are widely distributed enzymes found in highly varying amounts in tissues of the human body. The enzyme GST-pi in urine has been used as a marker of renal distal tubular cell damage. The present study was intended to evaluate urinary excretion of GST-pi and its relationship to other renal markers and to the status of oxidative stress in preterm neonates.
Methods: Levels of urinary GST-pi, N-acetyl-beta-glucosaminidase (a marker of proximal tubular damage), albumin (a marker of glomerular damage) and 8-hydroxy-2'-deoxyguanosine (a marker of oxidative stress) and serum creatinine were measured in preterm neonates at 1 and 4 weeks of age.
Results: The results showed that urinary excretion of GST-pi is increased in preterm neonates compared with reported values for healthy adults. No significant relationship was detected between urinary GST-pi and other markers for renal function. Urinary GST-pi showed significantly positive correlation with urinary 8-hydroxy-2'-deoxyguanosine at 1 and 4 weeks. Sick neonates treated with supplemental oxygen and mechanical ventilation showed significantly higher levels of GST-pi as well as 8-hydroxy-2'-deoxyguanosine than clinically stable neonates did at 4 weeks.
Conclusions: These results indicate the potential effect of systemic oxidative stress on urinary excretion of GST-pi. Further studies are necessary to explore the effect of oxidative conditions on expression of GST-pi in distal tubules in the human kidney.

DOI： 10.1111/j.1442-200x.2005.02123.x

PDTC and NO suppress CC chemokine production in TNF-alpha-stimulated human pulmonary microvascular endothelial cells

Y Mori, H Tsukahara, MZ Jiang, M Mayumi

RESPIRATORY MEDICINE 99 ( 8 ) 1068 - 1069 2005.8

Quantification of L-type fatty acid binding protein in the urine of preterm neonates

H Tsukahara, T Sugaya, K Hayakawa, Y Mori, M Hiraoka, A Hata, M Mayumi

EARLY HUMAN DEVELOPMENT 81 ( 7 ) 643 - 646 2005.7

Language：English Publisher：ELSEVIER IRELAND LTD

We measured urinary excretion of L-type fatty acid binding protein (LFABP) in preterm neonates on days 1, 5-10, and 25-30 of life. Urinary L-FABP levels (expressed as the ratio to creatinine) in preterm neonates were considerably higher than those of healthy adults. They did not change significantly during the study period. Urinary L-FABP levels showed significant positive correlation with those of urinary N-acetyl-beta-D-glucosaminidase activity on day 1, and with those of 8-hydroxy-2'-deoxyguanosine on days 25-30. These results suggest that L-FABP is expressed in the neonatal kidney. Our results may also point to potential effects of proximal tubular damage and oxidative stress on urinary excretion of L-FABP. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.earlhumdev.2005.03.012

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Effects of antioxidants and NO on TNF-alpha-induced adhesion molecule expression in human pulmonary microvascular endothelial cells

MZ Jiang, H Tsukahara, K Hayakawa, Y Todoroki, S Tamura, Y Ohshima, M Hiraoka, M Mayumi

RESPIRATORY MEDICINE 99 ( 5 ) 580 - 591 2005.5

Language：English Publisher：W B SAUNDERS CO LTD

Pro-inflammatory cytokines initiate the vascular inflammatory response via upregulation of adhesion molecules on the endothelium. Recent observations suggest that reactive oxygen intermediates may play a pivotal role in TNF-alpha signaling and upregulate gene expression. We therefore evaluated 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-kappa B) activation induced by TNF-alpha (10ng/mL) in cultured human pulmonary microvascular endothelial cells (PMVEC). Treatment of cells with TNF-alpha. for 4h significantly induced the surface expression of E-selectin and ICAM-1. Treatment with TNF-alpha. for 8h significantly induced the surface expression of E-selectin, ICAM-1 and VCAM-1. The upregulation of these adhesion molecules was suppressed significantly by pretreatment with PDTC or Sper-NO for 1 h. 8-Bromo-cyctic GMP (1 mM) had no such effect, suggesting that the NO donor's effect was non-cGMP-dependent. The mRNA expression of E-selectin, ICAM-1 and VCAM-1, and activation of NF-kappa B induced by TNF-alpha for 2h were decreased significantly by the above two pretreatments. N-acetytcysteine (10 mM) and S-nitroso-N-acetylpenicillamine (1 mM) had little inhibitory effects on the cell surface and mRNA expression of these adhesion molecules stimulated by TNF-alpha. Treatment with TNF-alpha for 4 h enhanced HL-60 leukocyte adhesion to human PMVEC, the effect of which was inhibited significantly by pretreatment with PDTC or Sper-NO. These findings indicate that both cell surface and mRNA expression of adhesion molecules in human PMVEC induced by TNF-alpha are inhibited significantly by pretreatment with PDTC or Sper-NO, possibly in part through blocking the activation of NF-kappa B. Although our in vitro results cannot be directly extrapolated to the in vivo situation, they suggest a potential therapeutic approach for intervention in cytokine-mediated inflammatory processes in the human lung. (c) 2004 Elsevier Ltd. All rights reserved.

DOI： 10.1016/rmed.2004.10.007

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Parameters for measurement of oxidative stress in diabetes mellitus: Applicability of enzyme-linked immunosorbent assay for clinical evaluation

E Noiri, H Tsukahara

JOURNAL OF INVESTIGATIVE MEDICINE 53 ( 4 ) 167 - 175 2005.5

Language：English Publishing type：Book review, literature introduction, etc. Publisher：LIPPINCOTT WILLIAMS & WILKINS

Investigations of the mechanisms involved in the onset and progression of diabetes have recently confronted the role of reactive oxygen species (ROS) and oxidative stress. Prolonged exposure to hyperglycemic conditions induces nonenzymatic glycation of protein via the so-called Maillard reaction, resulting in Schiff-base products and Amadori products that engender ROS production. These processes initiate and exacerbate micro- and macrovascular complications in diabetes. Increased oxidative stress is induced by excessive ROS production and inadequate antioxidant defenses. Recently, oxidative stress status markers have been associated directly with the severity and prognosis of diabetes. To examine oxidative stress, reliable and high-throughput methods are needed to examine large numbers of clinical samples. The emerging availability of enzyme-linked immunosorbent assay (ELISA) for oxidative stress status markers allows its application to assessment of various pathophysiologic conditions, including diabetes. This review outlines the recent achievements of ELISA application for clinical studies elucidating oxidative stress. It introduces the potential applicability of ELISA for investigating oxidative stress in diabetes.

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Salivary-type hyperamylasemia in theophylline poisoning

K Suzuki, Y Ohshima, Hata, I, H Tsukahara, N Omata, M Yasutomi, A Yamada, M Mayumi

PEDIATRICS INTERNATIONAL 47 ( 2 ) 209 - 210 2005.4

Concentrations of thioredoxin, a redox-regulating protein, in umbilical cord blood and breast milk

Y Todoroki, H Tsukahara, Y Ohshima, K Shukunami, K Nishijima, F Kotsuji, A Hata, K Kasuga, K Sekine, H Nakamura, J Yodoi, M Mayumi

FREE RADICAL RESEARCH 39 ( 3 ) 291 - 297 2005.3

Language：English Publisher：TAYLOR & FRANCIS LTD

Growing evidence indicates that oxidative stress occurs during the fetal-to-neonatal transition. Such stress plays an important role in the pathogenesis of many neonatal diseases. Thioredoxin (TRX), a redox-regulating protein with antioxidant activity, is induced in various cells against oxidative stress and is secreted extracellularly. This study was undertaken to examine the clinical and biological importance of TRX in the perinatal setting. We measured concentrations of TRX in umbilical cord blood and breast milk using a sandwich ELISA. Our study demonstrated that concentrations of TRX in umbilical cord blood were six to seven times higher than those in blood of healthy adults. This study also showed that umbilical concentrations of TRX were correlated significantly with the extent of prematurity of the newborn, and that they were elevated significantly in newborns of mothers with preeclampsia compared to those of mothers without preeclampsia. In contrast, concentrations of coenzyme Q(10) and vitamin E in umbilical blood were lower than adult blood levels. Breast milk concentrations of TRX during the early postpartum period were seven to eight times higher than those in blood of lactating women. Those of the coenzyme Q(10) were lower than adult blood levels, while those of vitamin E were comparable to adult blood levels. Our findings suggest that the systemic release of TRX is enhanced at birth, and that early breast milk is a rich source of this protein. Consequent high levels of TRX in newborns may provide a unique protective mechanism that allows the maintenance of redox balance during the fetal-to-neonatal transition.

DOI： 10.1080/10715760500053578

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Marked renal damage in a child with hydronephrosis infected by Trichosporon asahii

Y Mori, M Hiraoka, M Katsu, H Tsukahara, Y Mikami, M Mayumi

PEDIATRIC NEPHROLOGY 20 ( 2 ) 234 - 236 2005.2

Language：English Publisher：SPRINGER

We describe a case of urinary infection caused by Trichosporon asahii, which drastically aggravated renal function in a left hydronephrotic kidney. Previous implantation of a nephrostomy tube and a ureteral J-stent and administration of broad-spectrum antibiotics seemed to have predisposed the non-granulocytopenic child to the urinary fungal infection.

DOI： 10.1007/s00467-004-1731-6

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Conservative versus extirpative management in cases of placenta accreta

K Nishijima, K Shukunami, H Tsukahara, F Kotsuji

OBSTETRICS AND GYNECOLOGY 105 ( 1 ) 220 - 220 2005.1

早産児の代謝性骨疾患

塚原宏一

周産期医学 35 1671 - 1679 2005

会報編集委員会: 報告と編集後記

橋本剛太郎, 加藤英治, 清水紘昭, 塚原宏一, 寺尾正

平成17年度福井県小児科医会会報 34(10) 2005

栄養補助物質の使用: ビタミンの補充

塚原宏一, 塚原康代

周産期医学 35(増刊号) 474 - 483 2005

周産期のレドックス制御: 特に母乳の抗酸化作用の分析についての研究

塚原宏一

2003年度財団法人森永奉仕会研究奨励金成果報告書 2005

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) ( 5 ) 677 - 680 2005

免疫・炎症性疾患におけるレドックス・マーカーの現況

塚原宏一

臨床病理 53(8) 759 - 767 2005

生直後に著明な赤芽球増加,低血糖を呈した胎児水腫の極低出生体重児例

小倉一将, 塚原宏一, 巨田尚子, 佐藤周子, 古畑律代, 田村知史, 谷澤昭彦, 眞弓光文

小児科臨床 58 ( 8 ) 1691 - 1695 2005

Quantitative unspun-urine microscopy as a quick, reliable examination for bacteriuria

M Hiraoka, Y Hida, Y Mori, H Tsukahara, Y Ohshima, H Yoshida, M Mayumi

SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION 65 ( 2 ) 125 - 132 2005

Language：English Publisher：TAYLOR & FRANCIS AS

The diagnosis and treatment of urinary infection are often delayed, causing renal damage, largely because of the unavailability of quick, accurate, diagnostic examinations. Three hundred and twenty-five urine samples from 130 patients were examined for significant bacteriuria using the standard culture method. The urine samples were also examined using the Gram-stain method and quantitative unspun-urine microscopy. When particles could not be distinguished definitely as bacilli by quantitative microscopy, the unspun urine was examined on a slide glass using oil-immersion microscopy at x 1000 magnification. Significant bacteriuria in 37 urine samples was detected by bacterial culture. Using quantitative microscopy, rods were found in 30, cocci in a chain in 3, and indefinite particles in 44 samples. In the 44 indefinite samples, oil-immersion microscopy was able to distinguish rods in one, cocci in a chain in one, cocci in a cluster in two, and negative in 40, which were confirmed by culture as rods, streptococci, staphylococci, and negative, respectively. The quantitative microscopy method was similarly reliable (94.6% sensitivity, 99.3% specificity) for diagnosis of significant bacteriuria when compared with the Gram-stain method (89.2% sensitivity, 98.6% specificity). Quantitative unspun-urine microscopy, confirmed by oil-immersion, is a quick, reliable method for diagnosis of significant bacteriuria, and is considered to be useful for early diagnosis of urinary infection.

DOI： 10.1080/00365510510013514

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