Faculty Profiles - TSUKAHARA Hirokazu

Papers - TSUKAHARA Hirokazu

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Meatus tightly covered by the prepuce is associated with urinary infection Reviewed

M Hiraoka, H Tsukahara, Y Ohshima, M Mayumi

PEDIATRICS INTERNATIONAL 44 ( 6 ) 658 - 662 2002.12

Language：English Publishing type：Research paper (scientific journal) Publisher：BLACKWELL PUBLISHING ASIA

Background : Almost all newborns have phimosis, which is known as one of the risk factors for urinary infection. The present study analyzed which specific prepuce conditions correlated with the development of febrile urinary infection in Japanese male infants.
Methods : The subjects consisted of 100 children, 64 boys and 36 girls, with febrile urinary infection. Prepuces were classified by their retractability in the male patients and in 714 healthy boys.
Results : Ninety-four percent of first febrile urinary infections occurred before 7 months of age in boys, whereas only 37% of the girls had first infections by that age. The prepuce covered the external urethral meatus in 96% of the healthy boys aged 3 years or less. A gentle retraction maneuver could not uncover the urethral meatus in approximately 40% of the boys aged 0 6 months. The frequency started to decline spontaneously after that age. Male patients aged 0 6 months significantly more often had tightly covered meatus than did healthy neonates (85% vs 42%, P<0.0001).
Conclusions : These findings indicate that it is specifically those boys whose external urethral meatus are tightly covered with foreskin who constitute the high-risk group for urinary infection. Awareness of this observation should help with diagnosing and managing urinary infection in young boys.

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Methylenetetrahydrofolate reductase polymorphism in childhood primary focal segmental glomerulosclerosis Reviewed

C Zou, H Tsukahara, M Hiraoka, J Mizu, Y Todoroki, Y Ohshima, H Kimura, K Tsuzuki, M Mayumi

NEPHRON 92 ( 2 ) 449 - 451 2002.10

Language：English Publishing type：Research paper (scientific journal) Publisher：KARGER

Aim: The purpose of this study was to evaluate the association between the methylenetetrahydrofolate reductase (MTHFR) C/T polymorphism and the prevalence and course of focal segmental glomerulosclerosis (FSGS) in our pediatric population. Methods: Genotypes for MTHFR were determined in 15 primary FSGS patients (male/female, 6/9) and 238 control subjects (male/female, 110/128) by the polymerase chain reaction and restriction fragment length polymorphism method. Results: For the whole group, the genotype frequencies (CC/CT/TT) of MTHFR in FSGS and control subjects were almost comparable. The TT genotype was associated with early onset of the disease as compared with the CC genotype. Furthermore, all the patients with the TT genotype had steroid-resistant FSGS and developed into end-stage renal failure, while those carrying either CC or CT genotype did not. Conclusion: We speculate that the TT genotype may be associated with early development and progression of childhood FSGS. Confirmatory studies using larger and ethnically distinct populations are needed to reveal the role of homocysteine in FSGS with consideration of medical interventions. Copyright (C) 2002 S Karger AG, Basel.

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Methylenetetrahydrofolate reductase polymorphism in childhood primary focal segmental glomerulosclerosis. International journal

Chaochun Zou, Hirokazu Tsukahara, Masahiro Hiraoka, Jiang Mizu, Yukiko Todoroki, Yusei Ohshima, Hideki Kimura, Kazuo Tsuzuki, Mitsufumi Mayumi

Nephron 92 ( 2 ) 449 - 51 2002.10

Language：English Publishing type：Research paper (scientific journal)

AIM: The purpose of this study was to evaluate the association between the methylenetetrahydrofolate reductase (MTHFR) C/T polymorphism and the prevalence and course of focal segmental glomerulosclerosis (FSGS) in our pediatric population. METHODS: Genotypes for MTHFR were determined in 15 primary FSGS patients (male/female, 6/9) and 238 control subjects (male/female, 110/128) by the polymerase chain reaction and restriction fragment length polymorphism method. RESULTS: For the whole group, the genotype frequencies (CC/CT/TT) of MTHFR in FSGS and control subjects were almost comparable. The TT genotype was associated with early onset of the disease as compared with the CC genotype. Furthermore, all the patients with the TT genotype had steroid-resistant FSGS and developed into end-stage renal failure, while those carrying either CC or CT genotype did not. CONCLUSION: We speculate that the TT genotype may be associated with early development and progression of childhood FSGS. Confirmatory studies using larger and ethnically distinct populations are needed to reveal the role of homocysteine in FSGS with consideration of medical interventions.

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脳MRIにて脳梁膨大部に可逆性変化が認められたロタウイルス腸炎の1例

古畑律代, 中井昭夫, 塚原宏一, 谷澤昭彦, 眞弓光文, 石森佳幸, 河村泰孝, 東方美保, 松本和男

日本小児科学会雑誌 106 ( 9 ) 1324 - 1324 2002.9

Bone mineral status in ambulatory pediatric patients on long-term anti-epileptic drug therapy Reviewed

H Tsukahara, K Kimura, Y Todoroki, Y Ohshima, M Hiraoka, Y Shigematsu, Y Tsukahara, M Miura, M Mayumi

PEDIATRICS INTERNATIONAL 44 ( 3 ) 247 - 253 2002.6

Language：English Publishing type：Research paper (scientific journal) Publisher：BLACKWELL PUBLISHING ASIA

Background : For ambulatory pediatric outpatients, reports of abnormalities of bone metabolism associated with anti-epileptic drugs are inconsistent and may be difficult to interpret.
Methods : The effects of long-term anti-epileptic therapy (mainly valproic acid and/or carbamazepine) on bone mineral status were evaluated in ambulatory epileptic patients (seven males and 11 females) aged 5.5-15.9 years. Bone mineral density (BMD) at the lumbar spine was measured by dual-energy X-ray absorptiometry and markers of bone and mineral metabolism were determined.
Results : The mean BMD was decreased by 9% in our patients relative to the control, and five patients (all males) showed osteopenia, defined as BMD SD scores less than - 1.5. Serum levels of minerals, intact parathyroid hormone and 1alpha,25 (OH)(2) vitamin D were within the normal ranges. In most patients, serum levels of intact osteocalcin, carboxyterminal propeptide of type I procollagen and pyridinoline cross-linked telopeptide of type I collagen were reduced relative to the corresponding mean control values. The BB genotype by Bsm I restriction fragment length polymorphism, associated with low BMD, was not found in our patients. The dietary calcium intake in the osteopenic patients was significantly lower than that of the non-osteopenic patients.
Conclusions : Our results indicate that long-term anti-epileptic treatment induces a state of decreased bone turnover in children, resulting in osteopenia preferentially in males. The alterations may be due, at least in part, to direct effects of the drugs on bone cells; and that low calcium intake could be an aggravating factor for anti-epileptic-associated osteopenia.

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抗痙攣剤を長期に服用している外来患者における骨ミネラル代謝の評価

塚原宏一, 木村宏輝, 轟夕起子, 大嶋勇成, 平岡政弘, 重松陽介, 三浦雅一, 塚原康代, 眞弓光文

日本小児腎臓病学会雑誌 15 ( 1Suppl. ) 231 - 231 2002.6

尿路感染症による腎障害発生に関与する臨床所見の前方視的検討

平岡政弘, 橋本剛太郎, 土田晋也, 塚原宏一, 大嶋勇成, 眞弓光文

日本小児腎臓病学会雑誌 15 ( 1Suppl. ) 132 - 132 2002.6

Renal aplasia is the predominant cause of congenital solitary kidneys Reviewed

M Hiraoka, H Tsukahara, Y Ohshima, K Kasuga, Y Ishihara, M Mayumi

KIDNEY INTERNATIONAL 61 ( 5 ) 1840 - 1844 2002.5

Language：English Publishing type：Research paper (scientific journal) Publisher：BLACKWELL PUBLISHING INC

Background. Congenital solitary kidneys, which are susceptible to renal failure, have been considered mostly due to unilateral renal agenesis and partly due to renal aplasia. Risk of familial recurrence and of other associated anomalies is known to be much higher in renal agenesis than in renal aplasia. However, differential diagnosis between the two renal anomalies is difficult, and renal agenesis has been found much less frequently in ultrasound screening studies of fetuses than in autopsy studies.
Methods. In order to investigate the nature and incidence of the congenital solitary kidney, the present study performed ultrasound screening of the kidneys in 4000 newborn babies. A diagnosis of renal agenesis was made when ultrasound identified no renal parenchyma and renoscintigraphy showed no renal function, and renal aplasia when there was a renal parenchyma without any function.
Results. Primary screening detected 52 babies suspected of having small kidneys and one baby with a multicystic dysplastic kidney, but no baby with renal agenesis. Forty-seven of the 53 babies underwent a second ultrasound scanning at one month of age. Three small kidneys in three babies further decreased in size, had no function and were diagnosed as renal aplasia (which has an incidence rate of one in 1300). Follow-up ultrasound studies showed further regression in all three, which became very hard to distinguish by one year of age.
Conclusions. The present study showed that ultrasound in the neonatal period could identify the aplastic kidney, which had a reniform shape, not rudimentary, during the newborn period, and regressed rapidly thereafter. These findings indicate that most renal agenesis diagnosed clinically thus far might more correctly be renal aplasia.

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唾液腺由来の高アミラーゼ血症を呈したテオフィリン中毒の一例

鈴木孝二, 畑郁江, 塚原宏一, 小俣合歓子, 安冨素子, 大嶋勇成, 眞弓光文

日本小児アレルギー学会誌 15 ( 4 ) 491 - 491 2001.9

Involvement of thioredoxin in the regulation of growth hormone secretion in rat pituitary cell cultures Reviewed

Hata, I, Y Shigematsu, Y Ohshima, H Tsukahara, K Fujisawa, M Hiraoka, H Nakamura, H Masutani, J Yodoi, F Kotsuji, M Sudo, M Mayumi

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM 281 ( 2 ) E269 - E274 2001.8

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER PHYSIOLOGICAL SOC

We report here an examination of the effect of thioredoxin (TRX) on the secretion of growth hormone (GH) from rat anterior pituitary cells in vitro. Treatment of rat pituitary cells with growth hormone-releasing factor (GRF), but not GH, led to a significant increase in intracellular TRX protein levels. GRF, recombinant human TRX (rhTRX), and a combination thereof were all shown to induce immediate GH secretion from pituitary cells, as evidenced by perifusion experiments. RhTRX, but not other reducing agents such as beta -mercaptoethanol and N-acetyl-L-cysteine, augmented GRF-stimulated and -unstimulated GH secretion from rat pituitary cells in a dose-dependent manner. RhTRX did not significantly affect the GH mRNA expression of pituitary cells stimulated in the presence or absence of GRF. In addition, rhTRX-augmented GH secretion was not significantly affected by the presence of cycloheximide. Collectively, these findings suggest that TRX is induced by stimulation with GRF and plays a regulatory role in GH secretion from rat anterior pituitary cells by enhancing the secretion of stored GH, rather than by the synthesis of GH.

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Significance of ACE genotypes and medical treatments in childhood focal glomerulosclerosis Reviewed

C Hori, M Hiraoka, N Yoshikawa, K Tsuzuki, Y Yoshida, K Yoshioka, K Fujisawa, H Tsukahara, Y Ohshima, M Mayumi

NEPHRON 88 ( 4 ) 313 - 319 2001.8

Language：English Publishing type：Research paper (scientific journal) Publisher：KARGER

Background, There is little information on the significance of angiotensin-converting enzyme (ACE) genotypes and medical treatments in children with primary focal segmental glomerulosclerosis (FSGS). Methods: A multicenter retrospective study was performed on the role of ACE genotypes and medical treatments in 43 Japanese children with FSGS (20 males and 23 females), including 17 children who progressed to end-stage renal failure during the mean observation period of 6.9 (SD) 5.0 years. Results: The incidence of the D allele of the ACE gene was higher in the whole group of 43 children with FSGS and in a subgroup of 28 steroid-resistant FSGS children (p < 0.05) than in the 130 children of the healthy control group (0.48, 0.48, and 0.33, respectively). ACE genotypes did not affect renal survival in the whole FSGS group nor in the steroid-resistant subgroup. Among the 28 steroid-resistant children, treatment with ciclosporin was effective in delaying the development of end-stage renal failure (p = 0.044), independently of other treatment regimens. Conclusion: The present study of Japanese children with FSGS showed that the D allele of the ACE gene is associated with the development of FSGS, but not associated with the progression of FSGS which was greatly ameliorated with ciclosporin, irrespective of ACE genotypes. Copyright (C) 2001 S. Karger AG, Basel.

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Uroguanylin level in umbilical cord blood Reviewed

H Tsukahara, K Sekine, M Uchiyama, M Miura, M Nakazato, Y Date, W Tsunezawa, F Kotsuji, K Nishida, M Hiraoka, M Mayumi

PEDIATRICS INTERNATIONAL 43 ( 3 ) 267 - 269 2001.6

Language：English Publishing type：Research paper (scientific journal) Publisher：BLACKWELL PUBLISHING ASIA

Background: Uroguanylin is a novel natriuretic and diuretic peptide originally isolated from urine.
Methods: To determine whether uroguanylin has a physiologic role during the perinatal period, uroguanylin levels in umbilical cord plasma obtained at the time of delivery were measured by radioimmunoassay and compared with cord serum osmolality.
Results: Mean (+/-SD) cord plasma uroguanylin concentrations (8.8+/-2.1 fmol/mL) were higher compared with normal adult values. The extent of maturity, mode of delivery and gender did not appear to influence cord uroguanylin levels. The uroguanylin concentration had a significant positive correlation with cord serum osmolality.
Conclusion: These findings support some regulatory role of this peptide in perinatal renal and cardiovascular adaptation.

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Increased oxidative stress in childhood atopic dermatitis Reviewed

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

LIFE SCIENCES 69 ( 2 ) 223 - 228 2001.6

Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

Atopic dermatitis (AD) is a chronic inflammatory skin disease of unknown etiology. To examine the involvement of impaired homeostasis of oxygen/nitrogen radicals in childhood AD, we compared the levels of urinary 8-hydroxy-2'-deoxyguanosine (marker of oxidative stress), nitrite/nitrate (marker of nitric oxide synthesis) and selenium (marker of selenium store) in 27 children with AD to those of 25 healthy control children. Urinary 8-hydroxy-2'-deoxyguanosine was significantly higher and nitrite/nitrate levels were significantly lower in patients with AD than in the control. Urinary selenium levels were similar in both groups. Our findings suggest that impaired homeostasis of oxygen/nitrogen radicals and increased oxidative stress are involved in the pathophysiology of childhood AD, and indicate that suppression of oxidative stress might be a potentially useful strategy for the treatment of AD. (C) 2001 Elsevier Science Inc. All rights reserved.

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臍帯血液中における各種血管作動物質の計測

塚原宏一, 平岡政弘, 古畑律代, 大坂陽子, 江米足, 細川久美子, 小辻文和, 関根恭一, 三浦雅一, 眞弓光文

日本小児腎臓病学会雑誌 14 ( 1Suppl. ) 155 - 155 2001.5

No evidence for AT2R gene derangement in human urinary tract anomalies Reviewed

M Hiraoka, T Taniguchi, H Nakai, M Kino, Y Okada, A Tanizawa, H Tsukahara, Y Ohshima, Muramatsu, I, M Mayumi

KIDNEY INTERNATIONAL 59 ( 4 ) 1244 - 1249 2001.4

Language：English Publishing type：Research paper (scientific journal) Publisher：BLACKWELL SCIENCE INC

Background. It has been recently found that mice, especially males, with a disrupted angiotensin type 2 receptor (AT2R) gene, which is located on the X-chromosome, often have a range of congenital anomalies of the kidney and urinary tract (CAKUT), including renal hypoplasia, and that Caucasian male patients with ureteropelvic junction stenosis (UPJ) and multicystic dysplastic kidneys frequently have A-G transition in intron 1 of the AT2R gene. We have previously found that renal hypoplasia is remarkably predominant in Japanese boys.
Methods. We investigated sex ratios for the frequency of each CAKUT. The frequency of the A-G transition between the controls and 66 Japanese boys with CAKUT were compared. There was renal hypoplasia in 16, UPJ in 17, vesicoureteral in 20, and other anomalies in 13. We also investigated whether any mutations in A T2R genes were detectable in patients with renal hypoplasia.
Results. In contrast to mice with a disruption of the AT2R gene, the male-to-female ratios in human patients proved to be considerably variable: 16 for renal hypoplasia, 2.1 for UPJ, 0.8 for vesicoureteral, and 1.2 for others. The frequency of the A-G transition was not different between the control population and the patients with CAKUT [31 of 102 (30%) vs. 23 of 66 (35%), respectively]. A sequencing study disclosed no mutations in nine boys with renal hypoplasia.
Conclusions. These findings indicate that the AT2R gene may not play a major role in the development of renal hypoplasia and other CAKUT in humans, at least in the Japanese population.

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致死的経過をたどったWilson-Mikity症候群の新生児例:肺傷害の評価

轟夕起子, 塚原宏一, 川谷正男, 小畑浩一郎, 木村宏輝, 大嶋勇成, 平岡政弘, 眞弓光文

小児科診療 64 ( 3 ) 420 - 423 2001.3

Language：Japanese Publisher：(株)診断と治療社

症例は妊娠31週に帝王切開にて出生した女児で,生下時より胸部X線上全肺野び漫性の泡沫状陰影を認め,呼吸不全を呈しており,特徴的なX線像と高IgM血症の存在から重症型のWilson-Mikity症候群と診断された.集学的治療を施行したが,患児は生後62日目に多臓器不全にて死亡した.間質性肺炎の活動性の特異マーカーであるKL-6とサーファクタント蛋白質Dの血中濃度の測定結果では前者のみが異常高値を示した.この結果は慢性炎症の継続により,患児の肺の線維化が著しく高度になっていたことを示唆するものと考えられた

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エリスロマイシン少量持続投与中に肥厚性幽門狭窄症を発症した慢性肺疾患の超低出生体重児例 Reviewed

椎間優子, 塚原宏一, 古畑律代, 早川和代, 小渕信子, 中井昭夫, 谷澤昭彦, 平岡政弘, 眞弓光文

小児科臨床 55:1763-1766 2001

Relationship between gastric acid suppression and healing of peptic ulcers in children

M. Jiang, Z. M. Chen, H. Tsukahara, Y. Ohshima, B. Y. Ou, X. X. Chen, X. X. Wu, M. Mayumi

International Medical Journal 8 ( 3 ) 199 - 203 2001

Publishing type：Research paper (scientific journal)

Objective: This study was to examine the relationship between gastric acid suppression and healing of peptic ulcers in children. Materials and Methods: Twenty-seven patients (6-14 years old) with peptic ulcers confirmed by gastroscopy were randomized to receive ranitidine (n=16) and omeprazole (n=11) for five weeks. Intragastric 24hour pH monitoring was performed before treatment and repeated three times during the treatment: day one, week one, and week five. Endoscopy was repeated after five weeks of treatment. Results: All patients in the omeprazole group were healed, as were 10 of the 16 patients (63%) in the ranitidine group. The maximal suppression of gastric acidity by omeprazole appeared during the first week and continued for four weeks. For the ranitidine group, the gastric pH and duration with gastric pH > 3 remained almost stable in the healed patients, while the gastric acid suppressive effect attenuated significantly and disappeared at the end of the treatment in the unhealed patients. The Helicobacter pylori status after eradicative treatment was comparable between the healed and unhealed patients. Conclusion: These findings indicate that a higher degree and a longer duration of gastric acid suppression are beneficial for healing of peptic ulcers in children.

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川崎病患者における一酸化窒素(NO)産生の評価

塚原宏一, 斎藤正一, 西田公一, 大嶋勇成, 平岡政弘, 眞弓光文

日本小児アレルギー学会誌 14 ( 3 ) 382 - 382 2000.10

川崎病患者におけるMTHFR(methylenetetrahydrofolate reductase)遺伝子多型の検討

塚原宏一, 平岡政弘, 斎藤正一, 西田公一, 大嶋勇成, 木村秀樹, 下条文武, 眞弓光文

日本小児アレルギー学会誌 14 ( 3 ) 382 - 382 2000.10

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Papers - TSUKAHARA Hirokazu