研究者詳細 - 塚原　宏一

論文 - 塚原　宏一

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尿中一酸化窒素代謝物（ＮＯＸ｀－´）定量による小児の一酸化窒素（ＮＯ）産生の評価基礎データとその応用

塚原宏一, 堀親秀, 畑郁江, 土田晋也, 平岡政弘, 津村久美, 菊池清, 眞弓光文

日本小児腎臓病学会雑誌 11 ( 1 ) 79 - 83 1998年

記述言語：日本語出版者・発行元：The Japanese Society for Pediatric Nephrology

一酸化窒素 (NO) は多彩な生理活性を有するガス状ラジカルであり，ここ10年の間きわめて精力的な研究が展開されてきた。われわれは，小児におけるNOの生理学的・病態学的意義を明らかにするために，尿中の一酸化窒素代謝物濃度を指標として以下の臨床的研究を行ったので，その成果を紹介する。(1)正常小児における内因性NO産生の評価，(2)川崎病，気管支喘息の患者におけるNO産生の評価，(3)インスリン，L-アルギニンのNO合成系への作用に関する研究がその内容である。小児の病態生理においてNOがいかなる役割を果たしているのか不明のところが多く，今後の研究が期待される。

DOI： 10.3165/jjpn.11.79

その他リンク： http://search.jamas.or.jp/link/ui/1998196311

日本人小児における特発性膜性腎症の臨床経過および治療個人的考察

塚原宏一

日本小児腎臓病学会雑誌 11 ( 2 ) 203 - 208 1998年

記述言語：日本語出版者・発行元：The Japanese Society for Pediatric Nephrology

特発性膜性腎症 (IMN) に対しては，副腎皮質ステロイド剤や免疫抑制剤などが治療に用いられることが多いが，その評価に関しては統一的な見解はいまだない。本稿では，わが国の小児におけるIMN症例の臨床経過および治療の現況とそれらの特徴を集約してとらえ，諸外国の症例と対比させながら，日本人小児のIMNに対する管理方針について論じた。<br> 成人例よりも自然寛解率が高く，とくに欧米の患児よりも予後の良好な日本人小児のIMNの治療指針としては，現段階では次のように考えるのが妥当であろう。すなわち，ネフローゼ症候群を呈さない症例の場合は，一過性の可能性が高く，腎機能障害を残す危険性もきわめて低いので，ステロイドあるいは免疫抑制剤の治療を要しない。すなわち，対症療法のみを行う。ネフローゼ状態がある期間続く場合には，腎機能障害を呈する危険もありうるので，あるいは，ネフローゼ症候群そのものによる合併症を抑止する目的で，ステロイド剤を試みてもよい。また，免疫抑制剤については，日本人小児には原則として使用すべきではないと思われる。

DOI： 10.3165/jjpn.11.203

その他リンク： http://search.jamas.or.jp/link/ui/1999096910

Assessment of endogenous nitric oxide formation in newborns: Measurement of urinary nitrite and nitrate concentrations 査読

H Tsukahara, M Takeuchi, Hata, I, M Hiraoka, F Kotsuji, M Sudo, M Mayumi

BIOLOGY OF THE NEONATE 72 ( 5 ) 322 - 326 1997年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：KARGER

We measured the urinary nitrite and nitrate (NOx-) excretion, an index of endogenous nitric oxide formation, in term and preterm newborns on the ist and 4th days of age. In the infants of both groups, the urinary NOx- excretion significantly increased from the ist to the 4th day. The urinary NOx- excretion in preterm infants was significantly higher as compared with term babies on both days. Furthermore, the urinary NOx- excretion was significantly elevated in preterm infants with respiratory distress syndrome as compared with those without cardiopulmonary complications on the 4th day. These changes of urinary NOx- excretion in newborns strongly suggest the presence of an active physiological role for nitric oxide in the circulatory adaptation to extrauterine life.

Intermittent trimethoprim-sulfamethoxazole in children with vesicoureteral reflux 査読

C Hori, M Hiraoka, H Tsukahara, S Tsuchida, M Sudo

PEDIATRIC NEPHROLOGY 11 ( 3 ) 328 - 330 1997年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER VERLAG

The effectiveness of intermittent low-dose trimethoprim-sulfamethoxazole (TMP-SMZ) for the prophylaxis of recurrent urinary infection is well established in adults. The present study assessed the effectiveness and safety of intermittent low-dose TMP-SMZ in 35 children (24 boys, 11 girls, aged 1 month to 9 years, median age 5 months) with vesicoureteral reflux; 18 children had bilateral reflux. A total of 53 refluxing ureters were graded as I in 2, II in 16, III in 19, IV in 14, and V in 2 cases. The children were given 1 mg/kg body weight of trimethoprim together with 5 mg/kg of sulfamethoxazole at bedtime every other day for 6-50 months (mean +/- SD, 22.9 +/- 11.7 months). None of the boys had a recurrence of urinary infection, while 2 of the 11 girls had a total of 7 recurrences during the prophylaxis period, with a recurrence rate of 0.027 per patient month in girls. Both girls were over 3 years and had a mildly unstable bladder. Transient neutropenia (<1,000/mu l) developed in 2 infants during the prophylaxis period, but disappeared spontaneously. Intermittent low-dose TMP-SMZ seemed very effective for the prevention of recurrent urinary infection in children with ureteral reflux even of higher grades.

Endogenous nitric oxide production in Kawasaki disease 査読

H Tsukahara, K Kikuchi, M Matsuda, M Saito, Hata, I, S Tsuchida, M Sudo

SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION 57 ( 1 ) 43 - 47 1997年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SCANDINAVIAN UNIVERSITY PRESS

To evaluate in vivo nitric oxide production in Kawasaki disease (KD), urinary nitrite/nitrate (NOx) excretion was measured in 8 children with KD (age 1.1-2.7 years). Urinary NOx excretion was 0.66+/-0.22 mmol mmol(-1) creatinine (mean+/-SD) in the 8 children with KD in the initial stages. The levels were significantly increased compared with those of 12 age-matched healthy control subjects (0.35+/-0.08 mmol mmol(-1) creatinine). Urinary NOx excretion was serially determined in four patients. For each patient, there was a further rise in urinary NOx excretion from baseline levels coincident with the administration of intact-type gammaglobulin and aspirin. With clinical and laboratory improvement, however, urinary NOx excretion declined to the normal range. These findings suggest that endogenous nitric oxide production is enhanced in children with acute KD. Further studies are needed to clarify the role of nitric oxide in the pathogenesis and clinical course of KD.

Urinary nitrite nitrate excretion in infancy: Comparison between term and preterm infants 査読

H Tsukahara, M Hiraoka, C Hori, S Tsuchida, Hata, I, K Nishida, K Kikuchi, M Sudo

EARLY HUMAN DEVELOPMENT 47 ( 1 ) 51 - 56 1997年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCI IRELAND LTD

We measured urinary nitrite/nitrate (NOx-) excretion, an index of endogenous nitric oxide formation, in term and preterm infants aged 1 week and 1, 4, 7 months. In normal term infants, urinary NOx- excretion increased from 1 week to 1 month and then decreased until 4 months where it stabilized thereafter. Urinary NOx- excretion in preterm infants was significantly higher compared with term infants at I week of age. This finding suggests that the nitric oxide pathway in preterm infants may be activated compared with term infants in early life. With the reference values obtained in this study, this urinary marker can now be used for identifying infants with abnormal nitric oxide production.

Early detection of prune belly syndrome in utero by ultrasonography 査読

Ritsuyo Kobata, Hirokazu Tsukahara, Motohiro Takeuchi, Chikahide Hori, Masahiro Hiraoka, Toshiyuki Uchida, Fumikazu Kotsuji, Yasuhiko Ito, Kenichiro Okada, Masakatsu Sudo

Pediatrics International 39 ( 6 ) 705 - 709 1997年

記述言語：英語掲載種別：研究論文（学術雑誌）

A report is presented of a male infant with prune belly syndrome (PBS) in whom bladder enlargement was detected by ultrasound (US) as early as 13 weeks of gestation. Subsequent fetal US identified progressive urinary tract dilatation, ascites and oligohydramnios. At 22 weeks, the fetal bladder was drained under US guidance. A gradual resolution of oligohydramnios was detected on US performed after 26 weeks of gestation. Delivery by cesarean section was performed at 34 weeks of gestation. The newborn had typical features of PBS with a vesico-cutaneous fistula but did not show respiratory distress. Imaging studies showed hypoplastic left kidney, slightly dysplastic but functioning right kidney, megaureter, megacystis, vesicoureteral reflux and dilated prostatic urethra. The early detection of genitourinary system abnormalities and serial US suggest that a distal urethral obstruction may be the underlying mechanism of PBS. Spontaneous (or therapeutic) intra-uterine decompression of the bladder might ameliorate obstructive nephropathy and oligohydramnios, allowing adequate lung development. © 1997 Japan Pediatric Society.

DOI： 10.1111/j.1442-200X.1997.tb03673.x

一酸化窒素の骨代謝調節機構について

塚原宏一, 三浦雅一, 畠啓視, 木村宏輝, 堀親秀, 土田晋也, 平岡政弘, 山本和高, 石井靖, 須藤正克

日本小児腎臓病学会雑誌 10 ( 1 ) 17 - 21 1997年

記述言語：日本語出版者・発行元：The Japanese Society for Pediatric Nephrology

骨格系の代謝の基本は破骨細胞による骨吸収と骨芽細胞による骨形成の繰り返しである。これらの細胞は全身性因子の統御の下，様々な局所因子を分泌しauto-crine/paracrine 的に互いの機能調整を行っている。<br> 本稿では，その広範な生理的役割が注目されている一酸化窒素 (NO) が骨組織における強力な局所メディエータであることを支持する最近の研究成果を紹介した。とくに，成長期ラットの骨発育においてinducible型のNO合成酵素活性が重要な役割を果たすことを証明したわれわれの研究について詳述した。最後に，NOの骨代謝調節機構を対象とする研究の将来の方向性に触れた。

DOI： 10.3165/jjpn.10.17

その他リンク： http://search.jamas.or.jp/link/ui/1997189140

Possible Association of Xanthine Dehydrogenase/Xanthine Oxidase Activity with Nitric Oxide in vivo

Hirokazu Tsukahara, Masahiro Hiraoka, Chikahide Hori, Shinya Tsuchida, Koichiro Obata, Kiyoslii Kilcuchi, Masakatsu Sudo

Nephron 75 ( 1 ) 123 - 124 1997年

Comparative study between 18-and 16-gauge needle automated renal biopsy under orthogonal ultrasound guidance in children

Shinya Tsuchida, Masahiro Hiraoka, Chikahide Hori, Hirokazu Tsukahara, Shinichi Haruki, Shuhe Hayashi, Shinichi Fujisawa, Yukuo Konishi, Masakatsu Sudo

Nephron 75 ( 2 ) 238 1997年

Age-related changes ofurinary nitrite/nitrate excretion in normal children

Hirokazu Tsukahara, Masahiro Hiraoka, Chikahide Hori, Takeshi Miyanomae, Kiyoshi Kikuchi, Masakatsu Sudo

Nephron 76 ( 3 ) 307 - 309 1997年

記述言語：英語掲載種別：研究論文（学術雑誌）

We measured the urinary excretion of nitrite/nitrate, stable metabolites of nitric oxide, using the brucine method in 90 healthy normal children (47 boys and 43 girls), aged from 1.0 to 17.1 years, to establish the age-related normal range in children. The urinary nitrite/nitrate excretion was highest in the youngest children and decreased in an age-dependent manner to reach constant levels at about 12 years of agein both sexes. The data may be useful in identifying sick children with abnormal nitric oxide production. © 1997 S.Karger AG, Basel.

DOI： 10.1159/000190196

Congenitally small kidneys with reflux as a common cause of nephropathy in boys

Masahiro Hiraoka, Chikahide Hori, Hirokazu Tsukahara, Kenkou Kasuga, Yoshinori Ishihara, Masakatsu Sudo

Kidney International 52 ( 3 ) 811 - 816 1997年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nature Publishing Group

Congenital maldevelopment is sometimes found in small kidneys with ureteral reflux. However, the incidence of congenitally small kidneys and the frequency of its association with ureteral reflux remains unknown. Ultrasound scanning, performed in 4,000 apparently healthy neonates or young infants (males 2,129, females 1,871), detected 51 children suspected of having small kidneys. A careful ultrasound re-examination performed one month later in 45 of the 51 children confirmed small kidneys in eight children, one bilateral and seven unilateral. Dimercaptosuccinate (DMSA) renoscintigraphy revealed small kidneys with generally diminished uptake in six infants and no uptake unilaterally in the other two infants. One of the 12 children, who had normal findings on the initial scanning and subsequently developed urinary infection, was later diagnosed having unilateral small kidney with generally reduced DMSA uptake. All seven infants having small kidneys with reduced tracer uptake were male (incidence, 1:300 boys). All eight small kidneys in the seven boys and four of the six contralateral non-small kidneys were associated with ureteral reflux, while neither of the two infants with a non- functioning kidney had ureteral reflux. Serial ultrasounds documented the poor growth of all small kidneys. Thus, congenitally small kidneys with generally diminished DMSA uptake were highly associated with ureteral reflux and especially observed in boys.

DOI： 10.1038/ki.1997.398

Persistent hypercholesterolaemia in frequently relapsing steroid- responsive nephrotic syndrome

H. Tsukahara, S. Haruki, M. Hiraoka, C. Hori, M. Sudo

Journal of Paediatrics and Child Health 33 ( 3 ) 253 - 255 1997年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Blackwell Publishing

Objective: To investigate long-term changes of serum cholesterol levels in children with frequently relapsing steroid-responsive nephrotic syndrome (NS). Methodology: Serum cholesterol values just before and during or immediately after 'relapse' were reviewed and the incidence of hypercholesterolaemia (≤200 mg/dL) was determined in eight patients (M:F, 6:2). Results: The patients with frequently relapsing NS usually showed hypercholesterolaemia (mean incidence, 81%) just before 'relapse' during clinical remission, as well as in relapse (mean incidence, 96%). A high incidence of steroid therapy was also found in each case (mean, 89%) just before relapse. Conclusions: Our results demonstrate that children with frequently relapsing NS have prolonged periods of hypercholesterolaemia, even during clinical remission. It is suggested that serum lipid profiles be monitored carefully in such patients.

DOI： 10.1111/j.1440-1754.1997.tb01591.x

未熟児代謝性骨疾患の病態解析尿中コラゲン架橋(ピリジノリン,デオキシピリジノリン)排泄による評価

塚原宏一, 須藤正克, 三浦雅一

Osteoporosis Japan 4 ( 3 ) 528 - 531 1996年7月

Nitrite concentration in cerebrospinal fluid of infants: Evidence for enhanced nitric oxide production in Hemophilus influenzae meningitis 査読

Hirokazu Tsukahara, Yoshikazu Hara, Shinya Tsuchida, Yosuke Shigematsu, Yukuo Konishi, Kiyoshi Kikuchi, Masakatsu Sudo

Pediatrics International 38 ( 4 ) 420 - 422 1996年

Ultrasonography for the detection of ureteric reflux in infants with urinary infection

Masahiro Hiraoka, Gotaro Hashimoto, Shuhei Hayashi, Chikahide Hori, Shinya Tsuchida, Hirokazu Tsukahara, Yukuo Konishi, Masakatsu Sudo

Pediatrics International 38 ( 3 ) 248 - 251 1996年

記述言語：英語掲載種別：研究論文（学術雑誌）

Several less harmful methods than voiding cysto-urethrography for detecting significant ureteric reflux have been proposed. The present prospective study investigated whether ultrasonography was effective in identifying ureteric reflux in infants with their first febrile urinary infection. The subjects were 27 infants (24 boys and 3 girls) aged from 0 to 8 months. The urinary tract was scanned when the bladder was full, and before and during induced voiding. Infants with abnormal ultrasound findings underwent voiding cysto-urethrography. The other infants were followed and those who had a recurrence of urinary infection underwent voiding cystography. Ten children underwent cysto-urethrography, with eight refluxing ureters identified in six boys. Ultrasound revealed transient dilatation of the renal pelvis on voiding in five kidneys, transient dilatation of distal ureters in 12 and hydro-ureteronephrosis in two. Each of the five kidneys with pelvic dilatation on voiding was associated with ureteric reflux grades III or IV. Of the 17 children who did not undergo cysto-urethrography, only one had recurrence of urinary infection and was diagnosed with ureteric reflux. This girl was one of the three babies who were not scanned during voiding. More than half of the infants with febrile urinary infection were excluded from invasive examination without having recurrence of urinary infection. Thus, ultrasound scanning during voiding was effective for screening infants with their first urinary infection to detect significant ureteric reflux. 1996 Japan Pediatric Society.

DOI： 10.1111/j.1442-200X.1996.tb03479.x

A case of ureteral reflux identified by ultrasound

Masahiro Hiraoka, Iwao Fujimoto, Chikahide Hori, Hirokazu Tsukahara, Hironobu Akino, Kenichiro Okada, Masakatsu Sudo

Pediatrics International 38 ( 4 ) 374 - 376 1996年

記述言語：英語掲載種別：研究論文（学術雑誌）

Reflux nephropathy is known to be a major cause of renal failure in children. Vesico-ureteral reflux is usually diagnosed by voiding cysto-urethrography (VCG). However, it has been observed that conventional VCG is not always reliable for the diagnosis of ureteral reflux. In the case of a 5 year old girl with recurrent febrile urinary tract infection, VCG showed no ureteral reflux. Urodynamic study revealed a large bladder capacity and significant residual urine. Renal scintigram delineated a right renal scar. Simple ultrasound examination with videotape recording during voiding definitely demonstrated the presence of significant ureteral reflux when she voided, that is, there was marked dilatation of the right distal ureter and ballooning of the right renal pelvis on voiding, and quick refilling of the bladder concomitantly with the disappearance of the pelvic ballooning. Therefore, an ultrasound during voiding may be useful for diagnosing ureteral reflux in patients where a VCG does not reveal reflux. © 1996 Japan Pediatric Society.

DOI： 10.1111/j.1442-200X.1996.tb03510.x

Urinary Selenium Excretion in Infancy: Comparison between Term and Preterm Infants

Hirokazu Tsukahara, Yoji Deguchi, Masahiro Hiraoka, Chikahide Hori, Keiko Kimura, Tooru Kawamitsu, Yukuo Konishi, Yukinori Kusaka, Masakatsu Sudo

Neonatology 70 ( 1 ) 35 - 40 1996年

記述言語：英語掲載種別：研究論文（学術雑誌）

We evaluated the urinary excretion of selenium (Se), an essential component of glutathione peroxidase, in infants aged 1 week and 1, 4, and 7 months and examined the relationship between urinary Se and renal function. Daytime spot urine samples from a total of 80 infants were analyzed. The Se concentration in urine was measured by fluorometry, while the β2-microglobulin content, an index of renal tubular function, was determined by radioimmunoassay. In healthy term infants, the urinary Se excretion showed a peak level at 1 month of age. In contrast, the urinary Se concentration rapidly decreased in preterm infants from 1 week to 7 months postnatally. The level at 1 week in preterm infants was significantly higher than that in term infants, although the mean levels at 1 4, and 7 months were lower in preterm infants. The level of urinary Se did not correlate significantly with the β2-microglobulin concentration, either in term or preterm infants at any age investigated. Our results suggest that the renal excretion of Se probably reflects the body stores of Se and is not related directly to the renal function in infants. Urinary Se, a noninvasive marker of the Se status, may be used for diagnosis and follow-up of Se deficiency in infants. © 1996 S. Karger AG, Basel.

DOI： 10.1159/000244346

Urinary uric acid excretion in term and premature infants

H. Tsukahara, M. Hiraoka, C. Hori, S. Tsuchida, H. Uchida, K. Fujisawa, Y. Konishi, M. Sudo

Journal of Paediatrics and Child Health 32 ( 4 ) 330 - 332 1996年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Blackwell Publishing

Objective: To clarify postnatal changes in urinary uric acid (UA) excretion in normal term infants and to examine the effects of prematurity or illness on the UA excretion. Methodology: Measurements of urinary UA were performed in term and premature infants at the ages of 1 and 7 days and at 1 and 4 months, as well as at 7 months in term infants. Results: Urinary UA levels were lowest on day 7 in term infants. The levels were highest on day 1 in premature infants and remained significantly higher compared to term babies during the first month of life. Respiratory failure requiring ventilation and oxygen supply resulted in further significant elevation of urinary UA in premature infants. Conclusions: With the reference values obtained in the study reported here, urinary UA can now be used for the diagnosis and monitoring of inherited disorders of purine metabolism and for the assessment of oxygen radical insult to sick infants.

DOI： 10.1111/j.1440-1754.1996.tb02564.x

早期産出未熟児における尿中コラーゲン架橋排泄の測定の意義

塚原宏一, 三浦雅一, 畠啓視

小児科診療 58 ( 12 ) 2152 - 2156 1995年12月

記述言語：日本語出版者・発行元：(株)診断と治療社

生後1ヵ月の未熟児の尿中コラーゲン架橋(ピリジノリン,デオキシピリジノリン)排泄量を測定した.未熟児の尿中コラーゲン架橋排泄は著しく高値であった.又,それらが児の未熟性或いは臨床的容態の重篤度により,負の影響を受けることが示された

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