2021/12/24 更新

写真a

ツカハラ ヒロカズ
塚原 宏一
TSUKAHARA Hirokazu
所属
医歯薬学域 教授
職名
教授
外部リンク

学位

  • 医学博士 ( 福井医科大学 )

研究キーワード

  • 小児科学

  • Pediatrics

研究分野

  • ライフサイエンス / 胎児医学、小児成育学

  • ライフサイエンス / 腎臓内科学

  • ライフサイエンス / 胎児医学、小児成育学

学歴

  • 京都大学   医学部   医学科

    - 1985年

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    国名: 日本国

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  • 京都大学   Faculty of Medicine   医学科

    - 1985年

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経歴

所属学協会

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委員歴

  • 新生児内分泌研究会   幹事  

    2007年   

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    団体区分:学協会

    新生児内分泌研究会

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  • 発達腎研究会   実行委員  

    2006年   

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    団体区分:学協会

    発達腎研究会

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  • 日本NO学会   一般会員  

    2005年   

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    団体区分:学協会

    日本NO学会

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  • 中部日本小児腎臓病研究会   幹事  

    2005年   

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    団体区分:学協会

    中部日本小児腎臓病研究会

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  • 福井腎疾患研究会   世話人  

    2005年   

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    団体区分:学協会

    福井腎疾患研究会

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  • 中部日本糸球体腎炎談話会   幹事  

    2005年   

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    団体区分:学協会

    中部日本糸球体腎炎談話会

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  • 日本周産期新生児医学会   councilor  

    2004年   

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    団体区分:学協会

    日本周産期新生児医学会

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  • 日本周産期新生児医学会   評議員  

    2004年   

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    団体区分:学協会

    日本周産期新生児医学会

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  • 腎と免疫くずりゅうセミナー   世話人  

    2004年   

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    団体区分:学協会

    腎と免疫くずりゅうセミナー

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  • 福井県Infection Control Forum   幹事  

    2003年   

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    団体区分:学協会

    福井県Infection Control Forum

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  • 小児続発性骨粗鬆症研究会   世話人  

    2002年   

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    団体区分:学協会

    小児続発性骨粗鬆症研究会

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  • 日本小児腎臓病学会   評議員  

    2001年   

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    団体区分:学協会

    日本小児腎臓病学会

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  • 日本腎臓学会   評議員  

    1999年   

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    団体区分:学協会

    日本腎臓学会

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  • 北陸周産期・新生児研究会   理事  

    1997年   

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    団体区分:学協会

    北陸周産期・新生児研究会

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  • 国際小児腎臓病学会   一般会員  

    1989年   

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    団体区分:学協会

    国際小児腎臓病学会

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  • 小児骨代謝研究会   幹事  

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    団体区分:学協会

    小児骨代謝研究会

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  • 未熟児新生児医療研究会   世話人  

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    団体区分:学協会

    未熟児新生児医療研究会

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  • 日本周産期新生児医学会   評議員  

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    団体区分:学協会

    日本周産期新生児医学会

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  • 小児代謝性骨疾患研究会   幹事  

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    団体区分:学協会

    小児代謝性骨疾患研究会

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論文

  • A novel pathogenic variant p.Asp797Val in IFIH1 in a Japanese boy with overlapping Singleton-Merten syndrome and Aicardi-Goutières syndrome. 国際誌

    Kosei Hasegawa, Hiroyuki Tanaka, Natsuko Futagawa, Hiroyuki Miyahara, Yousuke Higuchi, Hirokazu Tsukahara

    American journal of medical genetics. Part A   188 ( 1 )   249 - 252   2022年1月

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    記述言語:英語  

    Pathogenic-activating variants of interferon induced with Helicase C domain 1 (IFIH1) cause Singleton-Merten (S-M) syndrome, which accompanies acro-osteolysis, loss of permanent teeth, and aortic calcification, as well as causing Aicardi-Goutières (A-G) syndrome, which shows progressive encephalopathy, spastic paraplegia, and calcification of basal ganglia. Recently, patients with overlapping syndromes presenting with features of S-M syndrome and A-G syndrome were reported. However, progression of clinical features of this condition has not been fully understood. We report a Japanese boy with a novel pathogenic IFIH1 variant who presented with clinical features of S-M syndrome and A-G syndrome.

    DOI: 10.1002/ajmg.a.62478

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  • Anti-high mobility group box 1 monoclonal antibody suppressed hyper-permeability and cytokine production in human pulmonary endothelial cells infected with influenza A virus. 国際誌

    Takahiro Namba, Mitsuru Tsuge, Masato Yashiro, Yukie Saito, Keyue Liu, Masahiro Nishibori, Tsuneo Morishima, Hirokazu Tsukahara

    Inflammation research : official journal of the European Histamine Research Society ... [et al.]   70 ( 10-12 )   1101 - 1111   2021年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: High mobility group box-1 (HMGB1) has been reported to be involved in influenza A virus-induced acute respiratory distress syndrome (ARDS). We studied the efficacy of an anti-HMGB1 mAb using an in vitro model of TNF-α stimulation or influenza A virus infection in human pulmonary microvascular endothelial cells (HMVECs). METHODS: Vascular permeability of HMVECs was quantified using the Boyden chamber assay under tumor necrosis factor-α (TNF-α) stimulation or influenza A virus infection in the presence of anti-HMGB1 mAb or control mAb. The intracellular localization of HMGB1 was assessed by immunostaining. Extracellular cytokine concentrations and intracellular viral mRNA expression were quantified by the enzyme-linked immunosorbent assay and quantitative reverse transcription PCR, respectively. RESULTS: Vascular permeability was increased by TNF-α stimulation or influenza A infection; HMVECs became elongated and the intercellular gaps were extended. Anti-HMGB1 mAb suppressed both the increase in permeability and the cell morphology changes. Translocation of HMGB1 to the cytoplasm was observed in the non-infected cells. Although anti-HMGB1 mAb did not suppress viral replication, it did suppress cytokine production in HMVECs. CONCLUSION: Anti-HMGB1 mAb might be an effective therapy for severe influenza ARDS.

    DOI: 10.1007/s00011-021-01496-5

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  • Trajectory of body mass index and height changes from childhood to adolescence: a nationwide birth cohort in Japan. 国際誌

    Naomi Matsumoto, Toshihide Kubo, Kazue Nakamura, Toshiharu Mitsuhashi, Akihito Takeuchi, Hirokazu Tsukahara, Takashi Yorifuji

    Scientific reports   11 ( 1 )   23004 - 23004   2021年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    To investigate the dynamics of body mass index (BMI) and height changes in childhood leading to obesity in adolescents. BMI Z-scores were calculated using the LMS (lambda-mu-sigma) method based on yearly height and weight information (age 1.5-15 years) from a nationwide Japanese birth cohort that started in 2001 (n = 26,711). We delineated the trajectories of BMI and height changes leading to obesity at age 15 years using mixed effect models. Children who became obese at the age of 15 years kept relatively high BMI z-scores through childhood for both genders, and had an increasing trend over time as opposed to the normal weight group, with an increasing slope during puberty. Early adiposity rebound was associated with overweight or obesity at the age of 15 years. Age at peak height velocity (APHV) occurred earlier in the obese/overweight group at age 15 years than in the normal weight group, and occurred later in the underweight group. Obese adolescents experienced early adiposity rebound timing and maintained a serial BMI z-score increase throughout childhood, with a greater slope at puberty. An earlier peak in height gain during puberty may have contributed to the observed patterns of BMI change.

    DOI: 10.1038/s41598-021-02464-z

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  • Current Insights into Atopic March. 国際誌

    Mitsuru Tsuge, Masanori Ikeda, Naomi Matsumoto, Takashi Yorifuji, Hirokazu Tsukahara

    Children (Basel, Switzerland)   8 ( 11 )   2021年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The incidence of allergic diseases is increasing, and research on their epidemiology, pathophysiology, and the prevention of onset is urgently needed. The onset of allergic disease begins in infancy with atopic dermatitis and food allergy and develops into allergic asthma and allergic rhinitis in childhood; the process is defined as "atopic march". Atopic march is caused by multiple immunological pathways, including allergen exposure, environmental pollutants, skin barrier dysfunction, type 2 inflammation, and oxidative stress, which promote the progression of atopic march. Using recent evidence, herein, we explain the involvement of allergic inflammatory conditions and oxidative stress in the process of atopic march, its epidemiology, and methods for prevention of onset.

    DOI: 10.3390/children8111067

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  • Sports participation and preterm birth: a nationwide birth cohort in Japan. 国際誌

    Kei Tamai, Naomi Matsumoto, Akihito Takeuchi, Makoto Nakamura, Kazue Nakamura, Misao Kageyama, Yosuke Washio, Hirokazu Tsukahara, Takashi Yorifuji

    Pediatric research   2021年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Children born preterm may be less physically active than children born term because of neurocognitive problems, reduced lung function, and poor physical fitness. We evaluated sports participation of children and adolescents who had been born preterm (<37 weeks) and early term (37-38 weeks) in 2001. METHODS: Data from a nationwide longitudinal survey (n = 47,015, including 2375 children born preterm) were analyzed. As indicators of sports participation, we used responses to questions about participation in sports clubs at 7 and 10 years old and in extracurricular school sports at 15 years old. RESULTS: Children born very preterm (25-31 weeks) and moderately to late preterm (32-36 weeks) were less likely to participate in sports clubs at 7, 10, and 15 years old than children born full term (39-41 weeks). Compared with children born full term, the adjusted risk ratios for participation in extracurricular school sports at 15 years old were 0.86 (95% confidence interval: 0.75-0.98) for children born very preterm, 0.92 (0.88-0.97) for children born moderately to late preterm, and 1.00 (0.98-1.02) for children born early term. CONCLUSIONS: Our findings suggest that preterm birth is associated with less participation in organized sports during childhood and adolescence than full-term birth. IMPACT: Research investigating associations between preterm birth and physical activity among children born in the 2000s is limited. This study shows that preterm birth was associated with less participation in organized sports during childhood and adolescence than full-term birth, especially in boys, and the participation in organized sports of children born preterm decreased as gestation shortened. During childhood, boys born early term were also less likely to participate in organized sports than boys born full term, suggesting a continuum with preterm births. These findings offer important additional insights into the limited evidence available for predicting future health outcomes for preterm infants.

    DOI: 10.1038/s41390-021-01808-9

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  • Preterm birth and Kawasaki disease: a nationwide Japanese population-based study. 国際誌

    Akihito Takeuchi, Takahiro Namba, Naomi Matsumoto, Kei Tamai, Kazue Nakamura, Makoto Nakamura, Misao Kageyama, Toshihide Kubo, Hirokazu Tsukahara, Takashi Yorifuji

    Pediatric research   2021年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Previous studies showed that preterm birth increased the risk for hospital admissions in infancy and childhood due to some acute diseases. However, the risk of preterm children developing Kawasaki disease remains unknown. In the present study, we investigate whether preterm birth increased the morbidity of Kawasaki disease. METHODS: We included 36,885 (34,880 term and 2005 preterm) children born in 2010 in Japan. We examined the association between preterm birth and hospitalization due to Kawasaki disease using a large nationwide survey in Japan. RESULTS: In log-linear regression models that were adjusted for children's characteristics (sex, singleton birth, and parity), parental characteristics (maternal age, maternal smoking, paternal smoking, maternal education, and paternal income), and residential area, preterm infants were more likely to be hospitalized due to Kawasaki disease (adjusted risk ratio: 1·55, 95% confidence interval: 1.01-2.39). We then examined whether breastfeeding status modified the potential adverse effects of preterm birth on health outcome. Preterm infants with partial breastfeeding or formula feeding had a significantly higher risk of hospitalization due to Kawasaki disease compared with term infants with exclusive breastfeeding. CONCLUSIONS: Preterm infants were at a high risk for Kawasaki disease, and exclusive breastfeeding might prevent this disease among preterm infants. IMPACT: Previous studies showed that preterm birth increased the risk for hospital admissions in infancy and childhood due to some acute diseases, however, the risk of preterm children developing Kawasaki disease remains unknown. This Japanese large population-based study showed that preterm infants were at a high risk for Kawasaki disease for the first time. Furthermore, this study suggested that exclusively breastfeeding might prevent Kawasaki disease among preterm infants.

    DOI: 10.1038/s41390-021-01780-4

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  • Head circumference in infants with nonopiate-induced neonatal abstinence syndrome. 国際誌

    Daisaku Morimoto, Yosuke Washio, Kazuki Hatayama, Tomoka Okamura, Hirokazu Watanabe, Junko Yoshimoto, Hirokazu Tsukahara

    CNS spectrums   26 ( 5 )   509 - 512   2021年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: No relationship has been reported between nonopiate neonatal abstinence syndrome (NAS) and anthropometric indices, including head circumference (HC). The purpose of this study was to determine the relationship between maternal nonopioid drug use and HC at birth in neonates with NAS. METHODS: This retrospective observational study included neonates born between January 1, 2010 and March 31, 2019, whose mothers had been taking antipsychotic, antidepressant, sedative, or anticonvulsant medications. The outcome measures were HCs of NAS infants and controls. RESULTS: Of 159 infants, 33 (21%) were diagnosed with NAS. There was no maternal opioid use among mothers during pregnancy. The HCs in the NAS group were significantly smaller than those in the control group. The median z-scores for HC at birth were -0.20 and 0.29 in the NAS group and the control group, respectively (P = .011). The median HCs at birth were 33.0 and 33.5 cm in the NAS group and the control group, respectively. Multivariate analysis revealed that maternal antipsychotic drug use and selective serotonin reuptake inhibitors were independently associated with NAS (P < .001 and P = .004, respectively). Notably, benzodiazepine use and smoking were not independent risk factors. CONCLUSIONS: The results suggest an association between maternal antipsychotic drug use and NAS, which was further associated with decreased HC. Careful monitoring of maternal drug use should be considered to improve fetal outcomes.

    DOI: 10.1017/S1092852920001522

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  • Reactive Oxygen Species and Antioxidative Defense in Chronic Obstructive Pulmonary Disease. 国際誌

    Akihiko Taniguchi, Mitsuru Tsuge, Nobuaki Miyahara, Hirokazu Tsukahara

    Antioxidants (Basel, Switzerland)   10 ( 10 )   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The respiratory system is continuously exposed to endogenous and exogenous oxidants. Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways, leading to the destruction of lung parenchyma (emphysema) and declining pulmonary function. It is increasingly obvious that reactive oxygen species (ROS) and reactive nitrogen species (RNS) contribute to the progression and amplification of the inflammatory responses related to this disease. First, we described the association between cigarette smoking, the most representative exogenous oxidant, and COPD and then presented the multiple pathophysiological aspects of ROS and antioxidative defense systems in the development and progression of COPD. Second, the relationship between nitric oxide system (endothelial) dysfunction and oxidative stress has been discussed. Third, we have provided data on the use of these biomarkers in the pathogenetic mechanisms involved in COPD and its progression and presented an overview of oxidative stress biomarkers having clinical applications in respiratory medicine, including those in exhaled breath, as per recent observations. Finally, we explained the findings of recent clinical and experimental studies evaluating the efficacy of antioxidative interventions for COPD. Future breakthroughs in antioxidative therapy may provide a promising therapeutic strategy for the prevention and treatment of COPD.

    DOI: 10.3390/antiox10101537

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  • Anaphylaxis after jellyfish ingestion with no history of stings: a pediatric case report. 国際誌

    Mitsuru Tsuge, Masanori Ikeda, Osamu Mitani, Masato Yasui, Hirokazu Tsukahara

    Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology   17 ( 1 )   99 - 99   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Jellyfish stings are known to induce allergic skin reactions; however, case reports of anaphylaxis after jellyfish ingestion have been increasing, especially in Asian countries. Some cases of anaphylaxis after jellyfish ingestion have been reported in patients with a previous history of frequent jellyfish stings. Herein, we report a pediatric patient with anaphylaxis after jellyfish ingestion with no history of jellyfish stings. CASE PRESENTATION: A 14-year-old girl developed two episodes of anaphylaxis, and her diet diaries revealed that edible jellyfish was common to the meals in both the anaphylaxis events. A skin prick test using five types of edible jellyfish products revealed a positive reaction to some jellyfish, and anaphylaxis was observed after the ingestion of jellyfish in an oral food challenge test. She had no history of jellyfish stings or frequent swimming in the ocean. The basophil activation test showed positive results on stimulation with extracts from various types of edible jellyfish. We observed serum immunoglobulin E (IgE) reactivity to purified jellyfish collagen and jellyfish acid-soluble extracts. Moreover, immunoblotting analysis showed IgE reactivity to two bands at approximately 40 and 70 kDa using purified jellyfish collagen, which may be a causative antigen. CONCLUSIONS: Edible salted jellyfish can be one of the causative foods of anaphylaxis. Clinicians should be aware of the possibility of anaphylactic reactions due to jellyfish ingestion even without a history of jellyfish stings.

    DOI: 10.1186/s13223-021-00601-x

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  • Terry's nails in an infant with liver cirrhosis. 国際誌

    Kazuhiro Uda, Mitsuru Tsuge, Kenji Shigehara, Masato Yashiro, Hirokazu Tsukahara

    Archives of disease in childhood   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1136/archdischild-2021-322953

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  • Association between Dental Caries and Influenza Infection in Children: A Japanese Nationwide Population-Based Study. 国際誌

    Naomi Matsumoto, Tomoka Kadowaki, Hirokazu Tsukahara, Takashi Yorifuji

    Children (Basel, Switzerland)   8 ( 9 )   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Dental caries is the most common chronic childhood disease. Recent studies have suggested that dental caries harbor respiratory infections in adults. We investigated the association between dental caries and influenza in children. In this study, 42,812 children aged 2.5 years, 38,540 children aged 5.5 years, and 34,124 children aged 10 years were included in the analysis from the Longitudinal Survey of Newborns in the 21st Century in Japan, which targeted all children born during a certain period in 2001. We used information on dental caries treated at hospitals and clinics in the past year as exposure and influenza as outcome during the observation periods (1.5-2.5, 4.5-5.5, and 9-10 years of age). We performed a log-binomial regression analysis, adjusting for potential confounders, and stratified analysis according to previous dental caries status. The presence of dental caries increased the incidence of influenza in all three target ages compared with the absence of dental caries. The incidence of influenza increased with the presence of current dental caries, regardless of the presence of past dental caries. These associations were observed irrespective of household income. Early detection and treatment of dental caries may reduce the risk of influenza in children.

    DOI: 10.3390/children8090780

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  • Association Between Eosinophilia and Late-onset Circulatory Collapse in Preterm Infants: A case-Control Study.

    Tomoka Okamura, Yosuke Washio, Hirokazu Watanabe, Hidehiko Nakanishi, Atsushi Uchiyama, Hirokazu Tsukahara, Satoshi Kusuda

    Acta medica Okayama   75 ( 4 )   505 - 509   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Late-onset circulatory collapse (LCC) in preterm infants is presumably caused by relative adrenal insufficiency. Because eosinophilia is known to be associated with adrenal insufficiency, we attempted to clarify the relation-ship between eosinophilia and LCC in preterm infants. We divided the cases of the infants (born at < 28 weeks' gestation) admitted to our neonatal intensive care unit in 2008-2010 into 2 groups: those diagnosed with LCC that received glucocorticoids (LCC group), and those who did not receive glucocorticoids (control group). We compared eosinophil counts between the 2 groups and between before and after glucocorticoid treatment in the LCC group. A total of 28 infants were examined: LCC group (n = 12); control group (n = 16). The peak eosin-ophil counts of the LCC group were significantly higher than those of the control group (median: 1.392 × 109/L vs. 1.033 × 109/L, respectively; p = 0.02). Additionally, in the LCC group, the eosinophil counts declined significantly after glucocorticoid treatment (0.877 × 109/L vs. 0.271 × 109/L, p = 0.003). Eosinophil counts in the LCC group were significantly higher than in the control group and decreased rapidly after gluco-corticoid treatment. These results indicate that eosinophilia may be a factor associated with LCC caused by adrenal insufficiency.

    DOI: 10.18926/AMO/62403

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  • 研究者の最新動向 インフルエンザ脳症における自然免疫を標的とした新規治療の探索

    津下 充, 西堀 正洋, 森島 恒雄, 塚原 宏一

    Precision Medicine   4 ( 6 )   596 - 599   2021年6月

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    記述言語:日本語   出版者・発行元:(株)北隆館  

    インフルエンザ脳症はインフルエンザ感染を契機にけいれんや意識障害を伴う。その病態は高サイトカイン血症による血液脳関門の障害が起きることで結果的に脳浮腫に至る。インフルエンザ脳症児の血液では特に「自然免疫」に関連した反応が強く起き、自然免疫メディエーターであるHigh Mobility Group Box-1(HMGB-1)は、インフルエンザ脳症児の血液中で高値を示す。岡山大学小児科では、インフルエンザ脳症における宿主の過剰な自然免疫反応を制御し、脳障害を軽減する次世代の炎症抑制療法の一つとして、HMGB-1をターゲットとした抗体治療の研究開発に取り組んでいる。(著者抄録)

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  • Genetic analysis in Japanese patients with osteogenesis imperfecta: Genotype and phenotype spectra in 96 probands. 国際誌

    Yousuke Higuchi, Kosei Hasegawa, Natsuko Futagawa, Miho Yamashita, Hiroyuki Tanaka, Hirokazu Tsukahara

    Molecular genetics & genomic medicine   9 ( 6 )   e1675   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Osteogenesis imperfecta (OI) is a rare connective-tissue disorder characterized by bone fragility. Approximately 90% of all OI cases are caused by variants in COL1A1 or COL1A2. Additionally, IFITM5 variants are responsible for the unique OI type 5. We previously analyzed COL1A1/2 variants in 22 Japanese families with OI through denaturing high-performance liquid chromatography screening, but our detection rate was low (41%). METHODS: To expand the genotype-phenotype correlations, we performed a genetic analysis of COL1A1/2 and IFITM5 in 96 non-consanguineous Japanese OI probands by Sanger sequencing. RESULTS: Of these individuals, 54, 41, and 1 had type 1 (mild), type 2-4 (moderate-to-severe), and type 5 phenotypes, respectively. In the mild group, COL1A1 nonsense and splice-site variants were prevalent (n = 30 and 20, respectively), but there were also COL1A1 and COL1A2 triple-helical glycine substitutions (n = 2 and 1, respectively). In the moderate-to-severe group, although COL1A1 and COL1A2 glycine substitutions were common (n = 14 and 18, respectively), other variants were also detected. The single case of type 5 had the characteristic c.-14C>T variant in IFITM5. CONCLUSION: These results increase our previous detection rate for COL1A1/2 variants to 99% and provide insight into the genotype-phenotype correlations in OI.

    DOI: 10.1002/mgg3.1675

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  • COVID-19 in Okayama Prefecture: Looking back and looking forward.

    Hirokazu Tsukahara, Tsukasa Higashionna, Mitsuru Tsuge, Junko Miyamura, Nobuchika Kusano

    Global health & medicine   3 ( 2 )   102 - 106   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    In Japan, clinical and experimental studies addressing COVID-19 have been increasing in number since early February 2020, with many case reports being published. Concurrently, many notifications and guidelines have been issued from the government and academic societies. Taking optimal measures at the prefectural level as well as the national level is necessary to prevent the spread of COVID-19. Surveying and analyzing details of the incidences of infected persons in each prefecture is extremely important. This report describes the epidemiological characteristics of COVID-19 observed in Okayama Prefecture, followed by discussion of the direction of public health actions to be taken in the future. We reiterate the crucial importance of reinforcing and maintaining current public health measures, including rapid and detailed compilation of information related to infected persons and their surroundings, appropriate blocking of viral transmission, and early containment of infected persons, to minimize the spread of infection especially during the overlapping epidemic period of influenza in Okayama Prefecture.

    DOI: 10.35772/ghm.2020.01104

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  • Outcomes of Right Ventricular Outflow Tract Reconstruction in Children: Retrospective Comparison Between Bovine Jugular Vein and Expanded Polytetrafluoroethylene Conduits. 国際誌

    Kenta Hirai, Kenji Baba, Takuya Goto, Daiki Ousaka, Maiko Kondo, Takahiro Eitoku, Yasuhiro Kotani, Shingo Kasahara, Shinichi Ohtsuki, Hirokazu Tsukahara

    Pediatric cardiology   42 ( 1 )   100 - 108   2021年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Bovine jugular vein (BJV) and expanded polytetrafluoroethylene (ePTFE) conduits have been described as alternatives to the homograft for right ventricular outflow tract (RVOT) reconstruction. This study compared RVOT reconstructions using BJV and ePTFE conduits performed in a single institution. The valve functions and outcomes of patients aged < 18 years who underwent primary RVOT reconstruction with a BJV or ePTFE conduit between 2013 and 2017 were retrospectively investigated. 44 patients (20 and 24 with BJV and ePTFE conduits, respectively) met the inclusion criteria. The mean follow-up time was 4.5 ± 1.5 years. No significant differences in peak RVOT velocity (1.8 ± 0.9 m/s vs 2.1 ± 0.9 m/s, P = 0.27), branch pulmonary stenosis (P = 0.50), or pulmonary regurgitation (P = 0.44) were found between the BJV and ePTFE conduit groups, respectively. Aneurysmal dilatation of the conduit was observed in 25.0% of the patients in the BJV conduit group but not in the ePTFE conduit group (P = 0.011). All the cases with aneurysmal dilatation of the BJV conduit were complicated with branch pulmonary stenosis up to 3.0 m/s (P = 0.004). No conduit infections occurred during the follow-up period, and no significant difference in conduit replacement (20.0% vs 8.3%, P = 0.43) was found between the BJV and ePTFE conduit groups, respectively. The outcomes of the RVOT reconstructions with BJV and ePTFE conduits were clinically satisfactory. Aneurysmal dilatation was found in the BJV conduit cases, with branch pulmonary stenosis as the risk factor.

    DOI: 10.1007/s00246-020-02458-0

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  • Clinical Factors Affecting the Dose Conversion Ratio from Intravenous to Oral Tacrolimus Formulation among Pediatric Hematopoietic Stem Cell Transplantation Recipients. 国際誌

    Kiichiro Kanamitsu, Takashi Yorifuji, Hisashi Ishida, Kaori Fujiwara, Kana Washio, Akira Shimada, Hirokazu Tsukahara

    Therapeutic drug monitoring   42 ( 6 )   803 - 810   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Tacrolimus is converted from intravenous to oral formulation for the prophylaxis of graft-versus-host disease when patients can tolerate oral intake and graft-versus-host disease is under control. Oral tacrolimus formulation presents poor bioavailability with intraindividual and interindividual variations; however, some factors affecting its blood concentration among pediatric hematopoietic stem cell transplantation (HCT) recipients are still unclear. This study aimed to identify the clinical factors affecting tacrolimus blood concentrations after switching its formulation. METHODS: Changes in the blood concentration/dose ratio (C/D) of tacrolimus in pediatric HCT recipients were analyzed after the switching of tacrolimus from intravenous to oral formulation. Clinical records of 57 pediatric patients who underwent allogenic HCT from January 2006 to April 2019 in our institute were retrospectively reviewed. The C/D of tacrolimus before discontinuation of intravenous infusion (C/Div) was compared with the tacrolimus trough level within 10 days after the initiation of oral administration (C/Dpo). Multiple linear regression analysis was performed to identify factors affecting (C/Dpo)/(C/Div). RESULTS: The constant coefficient of (C/Dpo)/(C/Div) was 0.1692 [95% confidence interval (CI), 0.137-0.2011]. The concomitant use of voriconazole or itraconazole and female sex were significant variables with a beta coefficient of 0.0974 (95% CI, 0.062-0.133) and -0.0373 (95% CI, -0.072 to -0.002), respectively. CONCLUSIONS: After switching of tacrolimus formulation, pediatric HCT recipients might need oral tacrolimus dose that is 5-6 and 3.5-4.5 times the intravenous dose to maintain tacrolimus blood concentrations and area under the concentration-time curve, respectively. With the concomitant use of voriconazole or itraconazole, an oral tacrolimus dose of 4-5 times the intravenous dose seemed appropriate to maintain blood tacrolimus concentration.

    DOI: 10.1097/FTD.0000000000000793

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  • Delayed Methotrexate Elimination after Administration of a Medium Dose of Methotrexate in a Patient with Genetic Variants Associated with Methotrexate Clearance.

    Yasuhisa Tatebe, Kiichiro Kanamitsu, Hirotaka Kanzaki, Hisashi Ishida, Kaori Fujiwara, Kana Washio, Yoshihisa Kitamura, Toshiaki Sendo, Akira Shimada, Hirokazu Tsukahara

    Acta medica Okayama   74 ( 6 )   545 - 550   2020年12月

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    記述言語:英語  

    Polymorphisms in methotrexate transporter pathways have been associated with methotrexate toxicities and clearance. Recent genome-wide association studies have revealed that the SLCO1B1 T521C variant is associated with methotrexate elimination. We present a case of a pediatric patient with acute lymphoblastic leukemia who suffered from persistently high plasma methotrexate concentrations and acute kidney injuries after the admin-istration of a medium dose of methotrexate. Subsequent genetic analysis showed that he was a carrier of dys-functional genetic variants associated with methotrexate clearance. This case highlights that polymorphisms of methotrexate transporter pathways can adversely affect methotrexate elimination in a clinically significant manner.

    DOI: 10.18926/AMO/61215

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  • Associations of Birth Weight for Gestational Age with Child Health and Neurodevelopment among Term Infants: A Nationwide Japanese Population-Based Study. 国際誌

    Kei Tamai, Takashi Yorifuji, Akihito Takeuchi, Yu Fukushima, Makoto Nakamura, Naomi Matsumoto, Yosuke Washio, Misao Kageyama, Hirokazu Tsukahara

    The Journal of pediatrics   226   135 - 141   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: To examine the association of specific Z-score categories of birth weight for gestational age with child health and neurodevelopment using a large nationwide survey in Japan, focusing on term infants. STUDY DESIGN: We included 36 321 children born in 2010. Hospitalization up to 66 months of age was used as an indicator of health status, and responses to questions about age-appropriate behaviors at 30 and 66 months of age were used to indicate neurobehavioral development. We conducted binomial log-linear regression analyses, controlling for child and parental variables. A restricted cubic spline function was used to model the relationship. RESULTS: Compared with children with birth weight appropriate for gestational age (-1.28 to 1.28 SDs of expected birthweight for gestational age), children who were small for gestational age (SGA) (<-1.28 SD) had higher risks of hospitalization and unfavorable neurobehavioral development, and the risks increased as SGA status became more severe. Compared with the appropriate for gestational age group, the adjusted risk ratios for hospitalization for all causes were 2.5 (95% CI, 1.7-3.6), 1.3 (95% CI, 1.1-1.6), and 1.1 (95% CI, 1.0-1.2) for children who were severely, moderately, and mildly SGA and 1.0 (95% CI, 0.9-1.1), 1.1 (95% CI, 0.9-1.2), and 1.4 (95% CI, 0.9-2.1) for children who were mildly, moderately, and severely large for gestational age, respectively. Severely large for gestational age children also had higher risks of unfavorable neurobehavioral development. These results were supported by spline analyses. CONCLUSIONS: Among term infants, the risks of unfavorable child health and neurodevelopment increased with the severity of SGA.

    DOI: 10.1016/j.jpeds.2020.06.075

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  • Polydactyly of the Foot Diagnosed from a Minor Nail Problem.

    Tomohiro Hiraoka, Haruka Senoo, Yuka Yamazaki, Kosaku Suenobu, Hirokazu Tsukahara

    Acta medica Okayama   74 ( 5 )   427 - 429   2020年10月

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    記述言語:英語  

    Polydactyly is one of the most common foot congenital anomalies. It is often detected immediately after birth, but the diagnosis can sometimes be delayed if the symptoms are less evident. A 2-year-old girl with a complaint of recurrent bleeding from the right toenail was diagnosed with foot polydactyly. She underwent corrective surgery, and her family was satisfied with the outcome. Although the diagnosis of polydactyly may be difficult in cases with minor nail problems, further radiographic evaluation will be needed for the improvement of the patient's quality of life.

    DOI: 10.18926/AMO/60803

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  • 肺血管内皮細胞を用いた重症インフルエンザ肺炎モデルの構築とhigh mobility group box 1抗体による肺血管透過性亢進の抑制効果

    難波 貴弘, 津下 充, 八代 将登, 塚原 宏一, 森島 恒雄, 西堀 正洋

    臨床とウイルス   48 ( 3 )   S84 - S84   2020年9月

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    記述言語:日本語   出版者・発行元:日本臨床ウイルス学会  

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  • A case of alveolar rhabdomyosarcoma showing concurrent responsive bone marrow lesions and refractory pancreatic lesions to pazopanib monotherapy. 国際誌

    Kiichiro Kanamitsu, Hisashi Ishida, Kaori Fujiwara, Kana Washio, Akira Shimada, Hirokazu Tsukahara

    Pediatric blood & cancer   67 ( 9 )   e28323   2020年9月

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    記述言語:英語  

    DOI: 10.1002/pbc.28323

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  • Laboratory changes during adrenocorticotropic hormone therapy associated with renal calcified lesions. 国際誌

    Hiroyuki Miyahara, Tomoyuki Akiyama, Kosei Hasegawa, Mari Akiyama, Makio Oka, Katsuhiro Kobayashi, Hirokazu Tsukahara

    Pediatrics international : official journal of the Japan Pediatric Society   62 ( 5 )   587 - 592   2020年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Renal calcified lesions are known as one of the complications during adrenocorticotropic hormone (ACTH) therapy for intractable epilepsy. However, laboratory changes during the therapy or laboratory features of high-risk cases with renal calcified lesions are yet to be clarified. METHODS: In this study, 43 patients with West syndrome aged ≤2 years were included. We retrospectively reviewed age and body mass index at the beginning of ACTH therapy, as well as the amount of fluid intake, daily urinary volume, and laboratory data during therapy. In addition, we studied the urinary sediment of the cases with renal calcified lesions diagnosed by computed tomography. RESULTS: After initiating ACTH treatment, urinary calcium (Ca)/creatinine ratio and urinary pH increased within 2 weeks. Urinary crystals and renal tubular epithelial cells (RTECs) in urinary sediment were frequently found in most cases. Urinary Ca levels, proteinuria or frequency of urinary crystals, and number of RTECs in the urinary sediment were significantly higher in patients with epithelial casts (ECs) or hematuria than in patients without these findings. Among the seven patients who underwent abdominal CT, ECs or hematuria were found only in those with renal calcified lesions. These findings suggested that patients with ECs or hematuria were more likely to have calcified lesions. CONCLUSIONS: The risk of renal calcified lesions increased after 2 weeks of ACTH treatment. Abnormal findings in urinary sediments might be an early sign of renal calcification during ACTH therapy.

    DOI: 10.1111/ped.14158

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  • マルチターゲット療法で加療中、胃腸炎を機に急性腎障害に至った全身性エリテマトーデスの一例

    宮原 宏幸, 石井 雅人, 茂原 研司, 津下 充, 八代 将登, 塚原 宏一

    日本小児腎臓病学会雑誌   33 ( 1 )   106 - 106   2020年4月

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    記述言語:日本語   出版者・発行元:(一社)日本小児腎臓病学会  

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  • Hemophagocytic lymphohistiocytosis complicating invasive pneumococcal disease: a pediatric case report. 国際誌

    Mitsuru Tsuge, Machiko Miyamoto, Reiji Miyawaki, Yoichi Kondo, Hirokazu Tsukahara

    BMC pediatrics   20 ( 1 )   15 - 15   2020年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is an infrequent but life-threatening disease due to excessive immune activation. Secondary HLH can be triggered by infections, autoimmune diseases, and malignant diseases. Streptococcus pneumoniae is a pathogenic bacterium responsible for invasive pneumococcal disease (IPD) such as meningitis and bacteremia. Although the pneumococcal conjugate vaccine (PCV) has led to reductions in IPD incidence, cases of IPD caused by serotypes not included in PCV are increasing. There are few reports of secondary HLH caused by IPD in previously healthy children. We herein report a rare case of a previously healthy boy with secondary HLH complicating IPD of serotype 23A, which is not included in the pneumococcal 13-valent conjugate vaccine (PCV-13). CASE PRESENTATION: An 11-month-old boy who had received three doses of PCV-13 was hospitalized with prolonged fever, bilateral otitis media, neutropenia and elevated C-reactive protein (CRP) levels. Blood culture on admission revealed S. pneumoniae, leading to a diagnosis of IPD. HLH was diagnosed based on a prolonged fever, neutropenia, anemia, hepatosplenomegaly, hemophagocytosis in the bone marrow, and elevated serum levels of triglycerides, ferritin, and soluble interleukin-2 receptor. He received broad-spectrum antibiotics and intravenous immunoglobulins for IPD and high-dose steroid pulse therapy and cyclosporine A for HLH; thereafter, his fever resolved, and laboratory findings improved. The serotype of the isolated S. pneumoniae was 23A, which is not included in PCV-13. CONCLUSIONS: It is important to consider secondary HLH as a complication of IPD cases with febrile cytopenia or hepatosplenomegaly, and appropriate treatment for HLH should be started without delay.

    DOI: 10.1186/s12887-020-1915-7

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  • Breastfeeding and risk of food allergy: A nationwide birth cohort in Japan. 国際誌

    Naomi Matsumoto, Takashi Yorifuji, Kazue Nakamura, Masanori Ikeda, Hirokazu Tsukahara, Hiroyuki Doi

    Allergology international : official journal of the Japanese Society of Allergology   69 ( 1 )   91 - 97   2020年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Although breastfeeding has been well-established as the preferred method for infant nutrition, its prophylactic effects on food allergy remain controversial. Infantile eczema has been linked to food allergy via percutaneous sensitization; however, this relationship has not been considered in previous studies. We aimed to uncover the prophylactic effects of breastfeeding on food allergy, focusing on eczema-mediated percutaneous sensitization. METHODS: This retrospective cohort study was based on 46,616 children from the Longitudinal Survey of Newborns in the 21st Century in Japan, begun in 2001. We classified participants into three groups based on infant feeding practices (exclusive breastfeeding, partial breastfeeding including only colostrum, and formula feeding only) and used information from at least one outpatient visit for food allergy during two observation periods (age 6-18 months and age 6-66 months) as health outcomes. We performed log-binomial regression analysis adjusted for potential confounders and stratified analysis according to infantile eczema status. RESULTS: Compared with formula feeding, partial breastfeeding including only colostrum reduced the risk of food allergy only in children with infantile eczema, (RR = 0.66, 95% CI: 0.46, 0.96 for age 6-66 months), whereas exclusive breastfeeding increased this risk in those without infantile eczema (RR = 2.41, 95% CI: 1.40, 4.15, age 6-66 months). The prophylactic effects of breastfeeding on food allergy in the infantile eczema group increased with shorter breastfeeding duration. CONCLUSIONS: Our results showed that breastfeeding, especially colostrum, had prophylactic effects on food allergy only among high-risk children with infantile eczema whereas prolonged breastfeeding increased the risk of food allergy.

    DOI: 10.1016/j.alit.2019.08.007

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  • Lupus anticoagulant-hypoprothrombinemia syndrome and immunoglobulin-A vasculitis: a report of Japanese sibling cases and review of the literature. 国際誌

    Kaori Fujiwara, Junya Shimizu, Hirokazu Tsukahara, Akira Shimada

    Rheumatology international   39 ( 10 )   1811 - 1819   2019年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare bleeding disorder caused by antiprothrombin antibodies. LAHPS is associated with systemic lupus erythematosus (SLE) or infections. We describe two Japanese brothers with immunoglobulin-A vasculitis (IgAV) who met the diagnostic criteria of LAHPS. They presented with palpable purpura and abdominal pain, and had a prolonged activated partial thromboplastin time (APTT) and prothrombin deficiency with the presence of lupus anticoagulant. Pediatric LAHPS was reviewed in abstracts from the Japan Medical Abstracts Society that were written in Japanese and PubMed or Web of Science-listed articles in English between 1996 and 2019. Including our cases, pediatric LAHPS has been reported in 40 Japanese and 46 non-Japanese patients. We summarized the clinical and laboratory characteristics of all 86 cases, and found only one Japanese LAHPS case with IgAV, except for our cases. Of the 86 cases, most were associated with infections followed by SLE. The presence of SLE, older age, lower prothrombin levels, severe bleeding symptoms, and positivity of immunoglobulin G anticardiolipin antibodies and anticardiolipin/β2-glycoprotein I antibodies and/or β2-glycoprotein I-dependent anticardiolipin antibodies had higher odds of requiring treatment. Measuring the APTT and prothrombin time (PT) might be required in patients with IgAV when they do not have a typical clinical course or distinctive symptoms. LAHPS should be considered with prolongation of the APTT and/or PT. Additionally, it is important to maintain a balance between the risk of thrombosis and hemorrhage when normalization of the PT and FII levels occurs in LAHPS cases under treatment.

    DOI: 10.1007/s00296-019-04404-7

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  • Clinical outcomes after the endovascular treatments of pulmonary vein stenosis in patients with congenital heart disease. 国際誌

    Yoshihiko Kurita, Kenji Baba, Maiko Kondo, Takahiro Eitoku, Shingo Kasahara, Tatsuo Iwasaki, Shinichi Ohtsuki, Hirokazu Tsukahara

    Cardiology in the young   29 ( 8 )   1057 - 1065   2019年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Pulmonary vein stenosis (PVS) is a condition with challenging treatment and leads to severe cardiac failure and pulmonary hypertension. Despite aggressive surgical or catheter-based intervention, the prognosis of PVS is unsatisfactory. This study aimed to assess the prognosis and to establish appropriate treatment strategies. METHODS: We retrospectively reviewed endovascular treatments for PVS (2001-2017) from the clinical database at the Okayama University Hospital. RESULTS: A total of 24 patients underwent PVS associated with total anomalous pulmonary venous connection and 7 patients underwent isolated congenital PVS. In total, 53 stenotic pulmonary veins were subjected to endovascular treatments; 40 of them were stented by hybrid (29) and percutaneous procedures (11) (bare-metal stent, n = 34; drug-eluting stent, n = 9). Stent size of hybrid stenting was larger than percutaneous stenting. Median follow-up duration from the onset of PVS was 24 months (4-134 months). Survival rate was 71 and 49% at 1 and 5 years, respectively. There was no statistically significant difference between stent placement and survival; however, patients who underwent bare-metal stent implantation had statistically better survival than those who underwent drug-eluting stent implantation or balloon angioplasty. Early onset of stenosis, timing of stenting, and small vessel diameter of pulmonary vein before stenting were considered as risk factors for in-stent restenosis. Freedom from re-intervention was 50 and 26% at 1 and 2 years. CONCLUSIONS: To improve survival and stent patency, implantation of large stent is important. However, re-intervention after stenting is also significant to obtain good outcome.

    DOI: 10.1017/S1047951119001495

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  • Neonatal hemochromatosis associated with rupture of esophageal varices. 国際誌

    Kazuki Hatayama, Yosuke Washio, Tomoka Okamura, Takuo Noda, Hirokazu Tsukahara

    Pediatrics international : official journal of the Japan Pediatric Society   61 ( 7 )   735 - 737   2019年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/ped.13908

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  • Exchange Transfusion and Cytarabine for Transient Abnormal Myelopoiesis in Hydrops Fetalis.

    Tomoka Okamura, Yousuke Washio, Junko Yoshimoto, Kazumasa Tani, Hirokazu Tsukahara, Akira Shimada

    Acta medica Okayama   73 ( 2 )   181 - 188   2019年4月

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    記述言語:英語  

    Most cases of transient abnormal myelopoiesis (TAM) in neonates with Down syndrome (DS) resolve spontaneously; however, DS-TAM neonates with hydrops fetalis (HF) show poor clinical outcomes. We report three infants with DS-TAM and HF who were treated with exchange transfusion (ET) followed by low-dose cytarabine (LD-CA). All of them survived without developing liver failure, acute leukemia, or other serious adverse events. Our results suggest that this combination treatment with ET and LD-CA would be safe, tolerable and effective as an novel approach for DS-TAM patients with HF.

    DOI: 10.18926/AMO/56655

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  • Balloon atrial septostomy in hypoplastic left heart syndrome with restrictive atrial septum. 国際誌

    Yosuke Fukushima, Kenji Baba, Maiko Kondo, Yoshihiko Kurita, Takahiro Eitoku, Yusuke Shigemitsu, Kenta Hirai, Hirokazu Tsukahara, Tatsuo Iwasaki, Shingo Kasahara, Yasuhiro Kotani, Shinichi Otsuki

    Pediatrics international : official journal of the Japan Pediatric Society   61 ( 4 )   339 - 344   2019年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Rashkind balloon atrial septostomy (BAS) can be challenging in infants with hypoplastic left heart syndrome (HLHS) and small atrial septal defect (ASD). METHODS: We retrospectively reviewed all infants with HLHS who underwent surgery and BAS between January 2006 and December 2015. The infants were divided into three groups: no BAS; catheter BAS; and open AS. Infants who underwent catheter BAS were divided into two groups based on atrial septal anatomy: standard and complex. RESULTS: Of the 70 patients, 57 (81%) underwent Glenn surgery. Subsequently, a significant difference in survival was observed: 86% (44/51), 91% (10/11), and 25% (2/8) in the no BAS, catheter BAS, and open AS groups, respectively (P = 0.0002). No significant difference was seen between the no BAS and the catheter BAS groups (P = 1.0). In the 56 patients who underwent catheterization after surgery, no intergroup differences in mean pulmonary artery pressure, pulmonary vascular resistance, or pulmonary artery index were found. We classified catheter BAS into standard (n = 5) and complex (n = 5) based on ASD location, and septum thickness. All patients in the standard group underwent complete Rashkind BAS, but in the complex group, only one patient underwent complete Rashkind BAS, with the remaining requiring initial static BAS (P = 0.048). Following septostomy, ASD size, ASD flow, and percutaneous oxygen saturation (SpO2 ) were not significantly different between the two groups. CONCLUSIONS: Catheter BAS is effective in infants with HLHS and a restrictive atrial septum. Infants with standard or complex atrial septum can achieve equivalent outcomes despite more patients often requiring static BAS.

    DOI: 10.1111/ped.13716

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  • Early childhood exposure to maternal smoking and Kawasaki Disease: A longitudinal survey in Japan. 国際誌

    Takashi Yorifuji, Hirokazu Tsukahara, Hiroyuki Doi

    The Science of the total environment   655   141 - 146   2019年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Kawasaki disease is the leading cause of acquired childhood heart disease in most developed countries, but the etiology of the disease is unknown. An aberrant immune response to some environmental triggers may play a role and involuntary exposure to tobacco smoke can alter immune functions. We thus prospectively examined the association between early childhood exposure to maternal smoking and the incidence of Kawasaki disease. We used a large, nationwide population-based longitudinal survey ongoing since 2010 and restricted participants to a total of 38,444 children for whom information on maternal smoking was available. Maternal smoking status was ascertained at 6months of age, and responses to questions about hospital admission for Kawasaki disease between the ages of 6 and 30months were used as outcome. We conducted binomial log-linear regression analyses adjusting for children's, parental, and residential factors with children of non-smoking mothers as our reference group. Maternal smoking increased the risk of admission, in particular for the period between 6 and 18months of age, in a dose-dependent manner. Compared with children of non-smoking mothers, the children of mothers who smoked had a risk ratio of 1.83 (95% confidence interval: 1.06, 3.35) for hospital admissions between 6 and 30months of age and a risk ratio of 2.69 (95% confidence interval: 1.56, 4.64) for hospital admissions between 6 and 18months of age. Early childhood exposure to maternal smoking may increase the risk of Kawasaki disease hospitalizations in childhood.

    DOI: 10.1016/j.scitotenv.2018.11.194

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  • Combined effect of anti-high-mobility group box-1 monoclonal antibody and peramivir against influenza A virus-induced pneumonia in mice. 国際誌

    Kazuki Hatayama, Nobuyuki Nosaka, Mutsuko Yamada, Masato Yashiro, Yosuke Fujii, Hirokazu Tsukahara, Keyue Liu, Masahiro Nishibori, Akihiro Matsukawa, Tsuneo Morishima

    Journal of medical virology   91 ( 3 )   361 - 369   2019年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Human pandemic H1N1 2009 influenza virus causes significant morbidity and mortality with severe acute lung injury due to the excessive inflammatory reaction, even with neuraminidase inhibitor use. The anti-inflammatory effect of anti-high-mobility group box-1 (HMGB1) monoclonal antibody (mAb) against influenza pneumonia has been reported. In this study, we evaluated the combined effect of anti-HMGB1 mAb and peramivir against pneumonia induced by influenza A (H1N1) virus in mice. Nine-week-old male C57BL/6 mice were inoculated with H1N1 and treated with intramuscularly administered peramivir at 2 and 3 days post-infection (dpi). The anti-HMGB1 mAb or a control mAb was administered at 2, 3, and 4 dpi. Survival rates were assessed, and lung lavage and pathological analyses were conducted at 5 and 7 dpi. The combination of peramivir with the anti-HMGB1 mAb significantly improved survival rate whereas the anti-HMGB1 mAb alone did not affect virus proliferation in the lungs. This combination therapy also significantly ameliorated histopathological changes, neutrophil infiltration, and macrophage aggregation by inhibiting HMGB1, inflammatory cytokines, and oxidative stress. Fluorescence immunostaining showed that the anti-HMGB1 mAb inhibited HMGB1 translocation from type I alveolar epithelial cells. In summary, combining anti-HMGB1 with conventional anti-influenza therapy might be useful against severe influenza virus infection.

    DOI: 10.1002/jmv.25330

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  • Panel-based next-generation sequencing identifies prognostic and actionable genes in childhood acute lymphoblastic leukemia and is suitable for clinical sequencing. 国際誌

    Hisashi Ishida, Akihiro Iguchi, Michinori Aoe, Takahide Takahashi, Kosuke Tamefusa, Kiichiro Kanamitsu, Kaori Fujiwara, Kana Washio, Takehiro Matsubara, Hirokazu Tsukahara, Masashi Sanada, Akira Shimada

    Annals of hematology   98 ( 3 )   657 - 668   2019年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Although the cure rate of ALL has greatly improved, a considerable number of patients suffer from relapse of leukemia. Therefore, ALL remains the leading cause of death from cancer during childhood. To improve the cure rate of these patients, precisely detecting patients with high risk of relapse and incorporating new targeted therapies are urgently needed. This study investigated inexpensive, rapid, next-generation sequencing of more than 150 cancer-related genes for matched diagnostic, remission, and relapse samples of 17 patients (3 months to 15 years old) with relapsed ALL. In this analysis, we identified 16 single-nucleotide variants (SNVs) and insertion/deletion variants and 19 copy number variants (CNVs) at diagnosis and 28 SNVs and insertion/deletion variants and 22 CNVs at relapse. With these genetic alterations, we could detect several B cell precursor ALL patients with high-risk gene alterations who were not stratified into the highest-risk group (5/8, 62.5%). We also detected potentially actionable genetic variants in about half of the patients (8/17, 47.1%). Among them, we found that one patient harbored germline TP53 mutation as a secondary finding. This inexpensive, rapid method can be immediately applied as clinical sequencing and could lead to better management of these patients and potential improvement in the survival rate in childhood ALL.

    DOI: 10.1007/s00277-018-3554-8

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  • Population-based longitudinal study showed that children born small for gestational age faced a higher risk of hospitalisation during early childhood. 国際誌

    Junko Yoshimoto, Takashi Yorifuji, Yosuke Washio, Tomoka Okamura, Hirokazu Watanabe, Hiroyuki Doi, Hirokazu Tsukahara

    Acta paediatrica (Oslo, Norway : 1992)   108 ( 3 )   473 - 478   2019年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIM: We examined the effects of being born small for gestational age (SGA) on the risk of being hospitalised for common diseases during childhood. METHODS: This Japanese nationwide, population-based longitudinal survey followed babies born before 42 weeks of gestation from 10 to 17 January and from 10 to 17 July 2001, using data from the Government's Longitudinal Survey of Babies in the 21st Century. Our study followed 41 268 children until 5.5 years of age: 39 107 full term (8.7% SGA) and 2161 preterm (15.5% SGA). We evaluated the relationship between SGA status and hospitalisation using their history of hospitalisation for common diseases and comparing full-term or preterm births. Logistic regression analysis, adjusted for potential confounders, estimated the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The full-term and preterm children who were born SGA were more likely to be hospitalised during infancy and early childhood than those born non SGA. The ORs for hospitalisation from six months to 18 months of age were 1.23 (95% CI: 1.10-1.37) for full-term and 1.67 (95% CI: 1.23-2.25) for preterm subjects. Higher risks of hospitalisation due to bronchitis, pneumonia, bronchial asthma and diarrhoea were also observed. CONCLUSION: Being born SGA was associated with all-cause and cause-specific hospitalisation in early childhood, particularly for term infants.

    DOI: 10.1111/apa.14507

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  • Serum Amino Acid Profiling in Citrin-Deficient Children Exhibiting Normal Liver Function During the Apparently Healthy Period. 査読 国際誌

    Teruo Miyazaki, Hironori Nagasaka, Haruki Komatsu, Ayano Inui, Ichiro Morioka, Hirokazu Tsukahara, Shunsaku Kaji, Satoshi Hirayama, Takashi Miida, Hiroki Kondou, Kenji Ihara, Mariko Yagi, Zenro Kizaki, Kazuhiko Bessho, Takahiro Kodama, Kazumoto Iijima, Tohru Yorifuji, Yasushi Matsuzaki, Akira Honda

    JIMD reports   43   53 - 61   2019年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Citrin (mitochondrial aspartate-glutamate transporter) deficiency causes the failures in both carbohydrate-energy metabolism and the urea cycle, and the alterations in the serum levels of several amino acids in the stages of newborn (NICCD) and adult (CTLN2). However, the clinical manifestations are resolved between the NICCD and CTLN2, but the reasons are still unclear. This study evaluated the serum amino acid profile in citrin-deficient children during the healthy stage. METHODS: Using HPLC-MS/MS analysis, serum amino acids were evaluated among 20 citrin-deficient children aged 5-13 years exhibiting normal liver function and 35 age-matched healthy controls. RESULTS: The alterations in serum amino acids characterized in the NICCD and CTLN2 stages were not observed in the citrin-deficient children. Amino acids involved in the urea cycle, including arginine, ornithine, citrulline, and aspartate, were comparable in the citrin-deficient children to the respective control levels, but serum urea was twofold higher, suggestive of a functional urea cycle. The blood sugar level was normal, but glucogenic amino acids and glutamine were significantly decreased in the citrin-deficient children compared to those in the controls. In addition, significant increases of ketogenic amino acids, branched-chain amino acids (BCAAs), a valine intermediate 3-hydroxyisobutyrate, and β-alanine were also found in the citrin-deficient children. CONCLUSION: The profile of serum amino acids in the citrin-deficient children during the healthy stage showed different characteristics from the NICCD and CTLN2 stages, suggesting that the failures in both urea cycle function and energy metabolism might be compensated by amino acid metabolism. SYNOPSIS: In the citrin-deficient children during the healthy stage, the characteristics of serum amino acids, including decrease of glucogenic amino acids, and increase of ketogenic amino acids, BCAAs, valine intermediate, and β-alanine, were found by comparison to the age-matched healthy control children, and it suggested that the characteristic alteration of serum amino acids may be resulted from compensation for energy metabolism and ammonia detoxification.

    DOI: 10.1007/8904_2018_99

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  • Associations of gestational age with child health and neurodevelopment among twins: A nationwide Japanese population-based study. 国際誌

    Kei Tamai, Takashi Yorifuji, Akihito Takeuchi, Makoto Nakamura, Yosuke Washio, Hirokazu Tsukahara, Hiroyuki Doi, Misao Kageyama

    Early human development   128   41 - 47   2019年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The prevalence of multiple births has recently increased. However, the association between gestational age and long-term morbidity among twins remains unclear. AIMS: To examine the association of gestational age with child health and neurological development in early childhood among twins. STUDY DESIGN: Population-based longitudinal study. SUBJECTS: We included 947 children from 479 pairs of twins with information on gestational age. OUTCOME MEASURES: Hospitalization was used as an indicator of physical health, and responses to questions about age-appropriate behaviors were used as an indicator of neurobehavioral development. We conducted binomial log-linear regression analyses, controlling for both child and maternal variables in the model. We accounted for correlations within the pairs with generalized estimating equations. RESULTS: The early term group (i.e., 37 to 38 weeks of gestation) had a lower risk of poor child health and unfavorable neurodevelopment compared with the full term group (≥39 weeks of gestation) and preterm group (<37 weeks of gestation). Compared with the early term group, the adjusted risk ratios for hospitalization for all causes during the period from 7 to 18 months of age was 2.2 (95% confidence interval: 1.3-3.8) for very preterm children (<32 weeks of gestation), 1.1 (0.8-1.6) for moderately and late preterm children (32 to 36 weeks of gestation), and 1.8 (1.0-3.2) for full term children. CONCLUSION: We observed a U-shaped association of gestational age with child health and neurodevelopment. The early term group had the lowest risk of poor outcomes among twins.

    DOI: 10.1016/j.earlhumdev.2018.11.005

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  • Novel AVPR2 variant in a male infant with nephrogenic diabetes insipidus who showed delayed head control.

    Kosei Hasegawa, Hiromi Ihoriya, Natsuko Futagawa, Yousuke Higuchi, Hiroki Tsuchiya, Takashi Shibata, Yumiko Hayashi, Katsuhiro Kobayashi, Hirokazu Tsukahara

    Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology   28 ( 4 )   155 - 158   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1297/cpe.28.155

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  • Long-stay pediatric patients in Japanese intensive care units: their significant presence and a newly developed, simple predictive score. 国際誌

    Emily Knaup, Nobuyuki Nosaka, Takashi Yorifuji, Kohei Tsukahara, Hiromichi Naito, Hirokazu Tsukahara, Atsunori Nakao

    Journal of intensive care   7   38 - 38   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: The length of stay (LOS) in intensive care units (ICUs) has been used as a good indicator not only for resource consumption but also for health outcomes of patients. However, data regarding pediatric LOS in Japanese ICUs are limited. The primary aim of this study was to characterize the Japanese pediatric ICU patients based on their LOS. Second, we aimed to develop a simple scoring system to predict long-stay pediatric ICU patients on admission. Methods: We performed a retrospective cohort study using consecutive pediatric data (aged < 16 years) registered in the Japanese Registry of Pediatric Acute Care (JaRPAC) from October 2013 to September 2016, which consisted of descriptive and diagnostic information. The factors for long-stay patients (LSPs; LOS > 14 days) were identified using multiple regression analysis, and subsequently, a simple predictive scoring system was developed based on the results. The validity of the score was prospectively tested using data from the JaRPAC registration from October 2016 to September 2017. Results: Overall, 4107 patients were included. Although LSPs were few (8.0% [n = 330]), they consumed 38.0% of ICU bed days (9750 for LSPs versus 25,659 overall). Mortality was seven times higher in LSPs than in short-stay patients (9.1% versus 1.3%). An 11-variable simple predictive scoring system was constructed, including Pediatric Index of Mortality 2 ≥ 1 (2 points), liver dysfunction (non-post operation) (2 points), post-cardiopulmonary resuscitation (1 point), circulatory disorder (1 point), post-operative management of liver transplantation (1 point), encephalitis/encephalopathy (1 point), myocarditis/cardiomyopathy (1 point), congenital heart disease (non-post operation) (1 point), lung tissue disease (1 point), Pediatric Cerebral Performance Category scores ≥ 2 (1 point), and age < 2 years (1 point). A score of ≥ 3 points yielded an area under the receiver operating characteristic curve (AUC) of 0.79, sensitivity of 87.0%, and specificity of 59.4% in the original dataset. Reproducibility was confirmed with the internal validation dataset (AUC 0.80, sensitivity 92.6%, and specificity 60.2%). Conclusions: Pediatric LSPs possess a significant presence in Japanese ICUs with high rates of bed utilization and mortality. The newly developed predictive scoring system may identify pediatric LSPs on admission.

    DOI: 10.1186/s40560-019-0392-2

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  • Wernicke's encephalopathy in a child with autism during chemotherapy for T-cell acute leukemia. 国際誌

    Kazumasa Zensho, Hisashi Ishida, Hiroki Nagai, Hirokazu Tsukahara, Akira Shimada

    Pediatrics international : official journal of the Japan Pediatric Society   60 ( 8 )   757 - 758   2018年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/ped.13615

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  • Epidemiology of Pediatric Acute Encephalitis/Encephalopathy in Japan.

    Shinichiro Goto, Nobuyuki Nosaka, Takashi Yorifuji, Tomoaki Wada, Yosuke Fujii, Masato Yashiro, Yosuke Washio, Kosei Hasegawa, Hirokazu Tsukahara, Tsuneo Morishima

    Acta medica Okayama   72 ( 4 )   351 - 357   2018年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We studied the etiology of pediatric acute encephalitis/encephalopathy (pAEE) using epidemiological data obtained from a nationwide survey in Japan. Two-step questionnaires were sent to the pediatric departments of hospitals throughout the country in 2007, querying the number of the cases during 2005-2006 as the first step, and asking for the details of clinical information as the second step. In all, 636 children with pAEE (age ≤ 15 years) were enrolled. For the known etiology of pAEE (63.5% of the total cases), 26 microbes and 2 clinical entities were listed, but the etiology of 36.5% remained unknown. Influenza virus (26.7%), exanthem subitum (12.3%), and rotavirus (4.1%) were the most common, and the incidence of pAEE peaked at the age of 1 year. This trend was common among all etiologies. Among the neurological symptoms observed at the onset of pAEE, seizures were observed more often in patients aged ≤ 3 years, although abnormal speech and behavior were also common in older children. Undesirable outcomes (death and neurological sequelae) occurred at high rates in patients with any known etiology other than mycoplasma. In conclusion, these findings provide comprehensive insight into pAEE in Japan.

    DOI: 10.18926/AMO/56170

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  • Cholesterol Metabolism Is Enhanced in the Liver and Brain of Children With Citrin Deficiency. 査読 国際誌

    Satoshi Hirayama, Hironori Nagasaka, Akira Honda, Haruki Komatsu, Takahiro Kodama, Ayano Inui, Ichiro Morioka, Shunsaku Kaji, Tsuyoshi Ueno, Kenji Ihara, Mariko Yagi, Zenro Kizaki, Kazuhiko Bessho, Hiroki Kondou, Tohru Yorifuji, Hirokazu Tsukahara, Kazumoto Iijima, Takashi Miida

    The Journal of clinical endocrinology and metabolism   103 ( 7 )   2488 - 2497   2018年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Context: Citrin-deficient infants present neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), which resolves at 12 months. Thereafter, they have normal liver function associated with hypercholesterolemia, and a preference for lipid-rich carbohydrate-restricted diets. However, some develop adult-onset type II citrullinemia, which is associated with metabolic abnormalities. Objectives: To identify the causes of hypercholesterolemia in citrin-deficient children post-NICCD. Design and Setting: We determined the concentrations of sterol markers of cholesterol synthesis, absorption, and catabolism by liquid chromatography-electrospray ionization-tandem mass spectrometry and evaluated serum lipoprotein profiles. Subjects: Twenty citrin-deficient children aged 5 to 13 years and 37 age-matched healthy children. Intervention: None. Main Outcome Measures: Relationship between serum lipoproteins and sterol markers of cholesterol metabolism. Results: The citrin-deficient group had a significantly higher high-density lipoprotein cholesterol (HDL-C) concentration than did the control group (78 ± 11 mg/dL vs 62 ± 14 mg/dL, P < 0.001), whereas the two groups had similar low-density lipoprotein cholesterol and triglyceride concentrations. The concentrations of markers of cholesterol synthesis (lathosterol and 7-dehydrocholesterol) and bile acids synthesis (7α-hydroxycholesterol and 27-hydroxycholesterol) were 1.5- to 2.8-fold and 1.5- to 3.9-fold, respectively, higher in the citrin-deficient group than in the control group. The concentration of 24S-hydroxycholesterol, a marker of cholesterol catabolism in the brain, was 2.5-fold higher in the citrin-deficient group. In both groups, the HDL-C concentration was significantly positively correlated with that of 27-hydroxycholesterol, the first product of the alternative bile acid synthesis pathway. Conclusions: HDL-C and sterol marker concentrations are elevated in citrin-deficient children post-NICCD. Moreover, cholesterol synthesis and elimination are markedly enhanced in the liver and brain of citrin-deficient children.

    DOI: 10.1210/jc.2017-02664

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  • Anti-high mobility group box-1 monoclonal antibody treatment of brain edema induced by influenza infection and lipopolysaccharide. 国際誌

    Nobuyuki Nosaka, Kazuki Hatayama, Mutsuko Yamada, Yousuke Fujii, Masato Yashiro, Hidenori Wake, Hirokazu Tsukahara, Masahiro Nishibori, Tsuneo Morishima

    Journal of medical virology   90 ( 7 )   1192 - 1198   2018年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Encephalopathy is a major cause of influenza-associated child death and severe neurological sequelae in Japan, highlighting the urgent need for new therapeutic strategies. In this study, we evaluated the effects of anti-high mobility group box-1 monoclonal antibody (α-HMGB1) treatment on brain edema induced by influenza A virus (IAV) and lipopolysaccharide in 4-week-old BALB/c female mice. The results showed that administration of 7.5 mg/kg α-HMGB1 1 h after IAV (A/Puerto Rico/8/34) inoculation significantly alleviated brain edema at 48 h after IAV inoculation, as confirmed by the suppression of Evans Blue dye leakage and matrix metallopeptidase-9 mRNA expression in the brain. Moreover, we also observed suppression of oxidative stress and different cytokines in IAV-inoculated mice. The expression of plasminogen activator inhibitor-1 was also attenuated following treatment with α-HMGB1. Notably, α-HMGB1 treatment had no effect on virus propagation in the lung. In summary, anti-HMGB1 treatment may improve the prognosis in cases with influenza-associated encephalopathy by attenuating brain edema and reducing the inflammatory responses induced by HMGB1.

    DOI: 10.1002/jmv.25076

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  • Incidence rate and characteristics of symptomatic vitamin D deficiency in children: a nationwide survey in Japan.

    Takuo Kubota, Hirofumi Nakayama, Taichi Kitaoka, Yosikazu Nakamura, Seiji Fukumoto, Ikuma Fujiwara, Yukihiro Hasegawa, Kenji Ihara, Sachiko Kitanaka, Satomi Koyama, Satoshi Kusuda, Haruo Mizuno, Keisuke Nagasaki, Koji Oba, Yuko Sakamoto, Noriyuki Takubo, Toshiaki Shimizu, Yusuke Tanahashi, Kosei Hasegawa, Hirokazu Tsukahara, Tohru Yorifuji, Toshimi Michigami, Keiichi Ozono

    Endocrine journal   65 ( 6 )   593 - 599   2018年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    There is concern that vitamin D deficiency is prevalent among children in Japan as well as worldwide. We conducted a nationwide epidemiologic survey of symptomatic vitamin D deficiency to observe its incidence rate among Japanese children. A questionnaire inquiring the number of new patients with vitamin D deficiency rickets and/or hypocalcemia for 3 years was sent to 855 randomly selected hospitals with a pediatrics department in Japan. In this survey, we found that 250 children were diagnosed with symptomatic vitamin D deficiency. The estimated number of patients with symptomatic vitamin D deficiency per year was 183 (95% confidence interval (CI): 145-222). The overall annual incidence rate among children under 15 years of age was 1.1 per 100,000 population (95% CI: 0.9-1.4). The second survey has provided detailed information on 89 patients with symptomatic vitamin D deficiency under 5 years of age in hospitals in the current research group. The nationwide and second surveys estimated the overall annual incidence rate of symptomatic vitamin D deficiency in children under 5 years of age to be 3.5 (2.7-4.2) per 100,000 population. The second survey revealed 83% had bowed legs, 88% had exclusive breastfeeding, 49% had a restricted and/or unbalanced diet and 31% had insufficient sun exposure among the 89 patients. This is the first nationwide survey on definitive clinical vitamin D deficiency in children in Japan. Elucidating the frequency and characteristics of symptomatic vitamin D deficiency among children is useful to develop preventative public health strategies.

    DOI: 10.1507/endocrj.EJ18-0008

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  • Analysis of factors associated with development of Bacille Calmette-Guérin inoculation site change in patients with Kawasaki disease. 国際誌

    Tooru Araki, Aya Kodera, Kunimi Kitada, Michimasa Fujiwara, Michiko Muraoka, Yoshiko Abe, Masanori Ikeda, Hirokazu Tsukahara

    The Journal of international medical research   46 ( 4 )   1640 - 1648   2018年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Objective The present study was performed to identify factors associated with a Bacille Calmette-Guérin (BCG) inoculation site change in patients with Kawasaki disease (KD). Methods Among patients who had received BCG vaccination and treatment for KD at our hospital from 2005 through 2016, 177 patients born in 2005 through 2016 were enrolled. The patients were divided into those with (n = 83, change group) and without (n = 94, no-change group) a BCG site change, and the patient demographics, clinical severity, blood examination results, and echocardiographic findings were compared between the two groups. Results The change group was younger at onset and had a shorter interval from vaccination to onset. A BCG site change was observed in patients who developed the onset of KD symptoms from 31 to 806 days after BCG vaccination. Multivariate analysis showed that the interval from vaccination was closely and positively associated with the BCG site change (hazard ratio = 0.995, 95% confidence interval = 0.993-0.997). Conclusion A BCG site change in patients with KD is most closely associated with the interval from BCG vaccination to onset.

    DOI: 10.1177/0300060518760462

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  • Blood asymmetric dimethylarginine and nitrite/nitrate concentrations in short-stature children born small for gestational age with and without growth hormone therapy. 査読 国際誌

    Hironori Nagasaka, Ichiro Morioka, Mayuko Takuwa, Mariko Nakacho, Mayumi Yoshida, Akihito Ishida, Satoshi Hirayama, Takashi Miida, Hirokazu Tsukahara, Tohru Yorifuji, Kazumoto Iijima

    The Journal of international medical research   46 ( 2 )   761 - 772   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SAGE Publications Ltd  

    Objective: To investigate the basal amino acid metabolism and impact of growth hormone (GH) therapy in short-stature children born small for gestational age (short SGA children). Methods: In this age-matched case-control study, the basal blood levels of amino acids, asymmetric dimethylarginine (ADMA), and nitrite/nitrate (NOx) were compared between 24 short SGA children and 25 age-matched normal children. Changes in these parameters were assessed for 12 months in 12 short SGA children initiating GH therapy (Group A) and 12 age-matched short SGA children without GH therapy (Group B). Results: The arginine levels were significantly lower in the short SGA than in normal children. The ADMA levels were significantly higher and NOx levels were significantly lower in the short SGA than normal children. In Group A, the ADMA level was significantly lower and NOx level was significantly higher at 6 months than at baseline. At 12 months, the ADMA level in Group A began to increase, but the NOx level remained the same. Group B showed no significant changes. Conclusions: This study is the first to show that ADMA is promoted and nitric oxide is suppressed in short SGA children and that GH therapy affects the production of ADMA and nitric oxide.

    DOI: 10.1177/0300060517723183

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  • Intrauterine and Early Postnatal Exposure to Particulate Air Pollution and Kawasaki Disease: A Nationwide Longitudinal Survey in Japan. 国際誌

    Takashi Yorifuji, Hirokazu Tsukahara, Saori Kashima, Hiroyuki Doi

    The Journal of pediatrics   193   147 - 154   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: To examine the effects of prenatal and postnatal exposure to particulate matter on Kawasaki disease (KD) occurrence, using data from a nationwide population-based longitudinal survey in Japan that began in 2010. STUDY DESIGN: Prenatal and postnatal suspended particulate matter concentrations were obtained at municipality level and assigned to participants based on their municipality of birth. We analyzed data from 30 367 participants with data on either exposure period. We used hospital admission for KD from 6 to 30 months of age as the main outcome of interest. We conducted a multilevel logistic regression analysis, adjusting for individual and municipality-level variables. RESULTS: Children who were exposed to higher levels of suspended particulate matter, in particular during pregnancy, were more likely to be hospitalized for KD. The ORs for ≥25 µg/m3 exposure compared with <20 µg/m3 exposure were 1.59 (95% CI 1.06, 2.38) for prenatal exposure and 1.41 (0.82, 2.41) for postnatal exposure. Prenatal exposure during mid-to-late gestation seemed to be more relevant for the increased risk. CONCLUSIONS: Early life exposure to particulate air pollution, in particular during pregnancy, is associated with an increased risk of KD hospital admission in early childhood in a nationally representative sample in Japan.

    DOI: 10.1016/j.jpeds.2017.10.012

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  • Serum Procalcitonin Levels in Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion. 国際誌

    Yosuke Fujii, Masato Yashiro, Mutsuko Yamada, Tomonobu Kikkawa, Nobuyuki Nosaka, Yukie Saito, Kohei Tsukahara, Masanori Ikeda, Tsuneo Morishima, Hirokazu Tsukahara

    Disease markers   2018   2380179 - 2380179   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Procalcitonin (PCT) is used as a biomarker in severe infections. Here, we retrospectively investigated levels of serum PCT, C-reactive protein (CRP), and inflammatory cytokines (IL-6, TNF-α, and IFN-γ) in the second phase of patients with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). Nine AESD pediatric patients (4 men, 5 women; AESD group) admitted to Okayama University Hospital from 2010 to 2016 were compared with 10 control patients with febrile seizures (FS) (3 men, 7 women; FS group). Mean PCT concentrations (ng/mL) in the AESD and FS groups were significantly different, at 9.8 ± 6.7 and 0.8 ± 0.9, respectively (p = 0.0011). CRP (mg/dL) were 0.79 ± 0.89 and 1.4 ± 1.0 (p = 0.21), respectively; IL-6 (pg/mL) were 449.7 ± 705.0 and 118.3 ± 145.4 (p = 0.20), respectively; TNF-α (pg/mL) were 18.6 ± 12.5 and 16.6 ± 6.0 (p = 0.67), respectively; and IFN-γ (pg/mL) were 79.6 ± 158.5 and 41.9 ± 63.7 (p = 0.56), respectively. Ratios of PCT to CRP were 27.5 ± 34.2 and 3.2 ± 6.8 (p < 0.0001), respectively. The sensitivity and specificity in the diagnosis of AESD using a cutoff of PCT/CRP ratio of 1.0 were 100% and 80%, respectively. These results suggest that PCT and the PCT/CRP ratio are useful in auxiliary diagnosis of the second stage of AESD, and in AESD, PCT is likely to increase through a different mechanism.

    DOI: 10.1155/2018/2380179

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  • Novel heterozygous mutation in TBX1 in an infant with hypocalcemic seizures.

    Kosei Hasegawa, Hiroyuki Tanaka, Yousuke Higuchi, Yumiko Hayashi, Katsuhiro Kobayashi, Hirokazu Tsukahara

    Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology   27 ( 3 )   159 - 164   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Patients with 22q11.2 deletion syndrome have characteristic facial appearance, palate abnormalities, hypoparathyroidism, thymic hypoplasia, and congenital heart disease. The 22q11.2 region includes TBX1 and 30 other genes. Analysis of Tbx1 transgenic mice showed that TBX1 was associated with the 22q11.2 deletion syndrome. In humans, TBX1 mutations have been reported in 22q11.2 deletion-negative patients with velocardiofacial syndrome or DiGeorge syndrome. Genotype-phenotype correlations are not fully understood in these patients. We report the case of an infant with a novel heterozygous TBX1 mutation who experienced hypocalcemic seizures. This patient had no palate abnormalities, cardiac anomalies, or the typical facial appearance observed in 22q11.2 deletion syndrome. The presence of thymic hypoplasia prompted us to perform G-banding, fluorescent in situ hybridization, and subsequent TBX1 analysis. We emphasize the importance of diagnosing thymic hypoplasia in hypocalcemic infants without 22q11.2 deletion for detecting TBX1 mutations.

    DOI: 10.1297/cpe.27.159

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  • Sorafenib treatment for papillary thyroid carcinoma with diffuse lung metastases in a child with autism spectrum disorder: a case report. 国際誌

    Yousuke Higuchi, Takayuki Motoki, Hisashi Ishida, Kiichiro Kanamitsu, Kana Washio, Takanori Oyama, Takuo Noda, Yasuko Tsurumaru, Ayumi Okada, Hirokazu Tsukahara, Akira Shimada

    BMC cancer   17 ( 1 )   775 - 775   2017年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Pediatric papillary thyroid carcinoma frequently presents with lymph node involvement and distant metastases. Sorafenib, an oral multikinase inhibitor, has been used to treat radioactive iodine (RAI) therapy-refractory thyroid carcinoma in adults; however, pediatric experience is limited. Medical procedures and hospitalization for children with autism spectrum disorder may be challenging. CASE PRESENTATION: An 11-year-old boy with autism spectrum disorder and moderate intellectual impairment presented with dyspnea on exertion with thyroid carcinoma and diffuses lung metastases. Total thyroidectomy and adjuvant RAI therapy is the standard treatment; however, the latter therapy was impractical because of his respiratory status and challenging behaviors. He was therefore started on sorafenib 200 mg/day (150 mg/m2/day) and this dosage was increased to 400 mg/day (300 mg/m2/day). The adverse effects were mild and tolerable. After administration of medication, his dyspnea improved and surgery was performed. We attempted to administer RAI therapy after surgery; however, we abandoned it because he had difficulty taking care of himself according to isolation room rules. Thyrotropin suppression therapy was therefore started and sorafenib treatment (400 mg/day) resumed. Follow-up imaging showed regression of pulmonary metastases. The metastases have remained stable for over 24 months on continuous sorafenib treatment without serious adverse events. CONCLUSION: We inevitably used sorafenib as an alternative to standard therapy because of the patient's specific circumstances. Individualized strategies for pediatric cancer patients with autism spectrum disorder are needed.

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  • Childhood cancer survivors: Anxieties felt after treatment and the need for continued support. 国際誌

    Naoko Iwai, Akira Shimada, Atsushi Iwai, Sonoe Yamaguchi, Hirokazu Tsukahara, Megumi Oda

    Pediatrics international : official journal of the Japan Pediatric Society   59 ( 11 )   1140 - 1150   2017年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Childhood cancer survivors (CCS) and their family members continue to live in fear even after treatment is concluded due to concerns about late effects and recurrences. The consequent long-term psychological burden requires long-term follow up suited to the anxieties and needs of CCS, hence the need for the present survey. METHODS: We conducted a questionnaire survey at medical facilities in the Chugoku and Shikoku regions of Japan with CCS who had survived for at least 5 years following treatment, and their family members. RESULTS: A total of 30 CCS (53%) and 27 CCS family members (47%) answered the questionnaires. The median age of the CCS and their family members (CCS parents) was 23 years and 51.5 years, respectively. The most common diagnosis was acute lymphoblastic leukemia (47%) and the median length of follow up after the conclusion of treatment was 11 years. The percentage of participants who responded that they knew about late effects was significantly lower among CCS than among CCS parents. Almost no significant difference was observed between CCS and CCS parents regarding anxieties at specific life stages. The main consultants for CCS and CCS parents were their family, but they sought opportunities for casual consultation for current worries outside the family. CONCLUSIONS: It is necessary for medical facilities not only to provide medical support, but also to establish a place where they can provide centralized consultation for the anxieties of CCS and their parents.

    DOI: 10.1111/ped.13390

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  • Gene expression analysis of hypersensitivity to mosquito bite, chronic active EBV infection and NK/T-lymphoma/leukemia. 国際誌

    Kana Washio, Takashi Oka, Lamia Abdalkader, Michiko Muraoka, Akira Shimada, Megumi Oda, Hiaki Sato, Katsuyoshi Takata, Yoshitoyo Kagami, Norio Shimizu, Seiichi Kato, Hiroshi Kimura, Kazunori Nishizaki, Tadashi Yoshino, Hirokazu Tsukahara

    Leukemia & lymphoma   58 ( 11 )   2683 - 2694   2017年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The human herpes virus, Epstein-Barr virus (EBV), is a known oncogenic virus and plays important roles in life-threatening T/NK-cell lymphoproliferative disorders (T/NK-cell LPD) such as hypersensitivity to mosquito bite (HMB), chronic active EBV infection (CAEBV), and NK/T-cell lymphoma/leukemia. During the clinical courses of HMB and CAEBV, patients frequently develop malignant lymphomas and the diseases passively progress sequentially. In the present study, gene expression of CD16(-)CD56(+)-, EBV(+) HMB, CAEBV, NK-lymphoma, and NK-leukemia cell lines, which were established from patients, was analyzed using oligonucleotide microarrays and compared to that of CD56brightCD16dim/- NK cells from healthy donors. Principal components analysis showed that CAEBV and NK-lymphoma cells were relatively closely located, indicating that they had similar expression profiles. Unsupervised hierarchal clustering analyses of microarray data and gene ontology analysis revealed specific gene clusters and identified several candidate genes responsible for disease that can be used to discriminate each category of NK-LPD and NK-cell lymphoma/leukemia.

    DOI: 10.1080/10428194.2017.1304762

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  • A novel mutation in the COL2A1 gene in a patient with Stickler syndrome type 1: a case report and review of the literature. 国際誌

    Yousuke Higuchi, Kosei Hasegawa, Miho Yamashita, Hiroyuki Tanaka, Hirokazu Tsukahara

    Journal of medical case reports   11 ( 1 )   237 - 237   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Stickler syndrome is a group of collagenopathies characterized by ophthalmic, skeletal, and orofacial abnormalities, with the degree of symptoms varying among patients. Mutations in the COL2A1, COL11A1, and COL11A2 procollagen genes cause Stickler syndrome. Marshall syndrome, caused by a COL11A1 mutation, has clinical overlap with Stickler syndrome. CASE PRESENTATION: A 2-year-old Japanese boy was presented to our hospital with short stature (79.1 cm, -2.52 standard deviation). His past medical history was significant for soft cleft palate and bilateral cataracts. He had a flat midface, micrognathia, and limitations in bilateral elbow flexion. Radiographs showed mild spondyloepiphyseal dysplasia. Initially, we suspected Marshall syndrome, but no mutation was identified in COL11A1. At 8 years old, his height was 116.2 cm (-1.89 standard deviation), and his orofacial characteristics appeared unremarkable. We analyzed the COL2A1 gene and found a novel heterozygous mutation (c.1142 G > A, p.Gly381Asp). CONCLUSIONS: In this case report, we identify a novel missense mutation in the COL2A1 gene in a patient with Stickler syndrome type 1, and we describe age-related changes in the clinical phenotype with regard to orofacial characteristics and height. Genetic analysis is helpful for the diagnosis of this clinically variable and genetically heterogeneous disorder.

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  • Metabolic pathway catalyzed by Vanin-1 pantetheinase plays a suppressive role in influenza virus replication in human alveolar epithelial A549 cells. 国際誌

    Nobuko Yamashita, Masato Yashiro, Hirohito Ogawa, Hikaru Namba, Nobuyuki Nosaka, Yousuke Fujii, Tsuneo Morishima, Hirokazu Tsukahara, Masao Yamada

    Biochemical and biophysical research communications   489 ( 4 )   466 - 471   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Our previous analysis of gene expression profiles in the peripheral blood from patients with influenza A (H1N1) pdm09 pneumonia revealed elevated transcription levels of the vanin-1 (vascular non-inflammatory molecule 1, VNN1) gene, which encodes an epithelial ectoenzyme with pantetheinase activity involved in recycling coenzyme A. Here, to elucidate the role of VNN1 in influenza A virus (IAV) H1N1 infection, we investigated the change of VNN1 expression in the context of IAV infection and the effects of its related substances, i.e., its direct substrate pantetheine and its two metabolites pantothenic acid and cysteamine on the replication of IAV in the human alveolar epithelial carcinoma cell line A549. The messenger RNA expression of VNN1 in A549 cells was significantly increased (by 4.9-fold) after IAV infection under an elevated concentration of pantetheine. Moreover, VNN1 mRNA levels were elevated by > 100-fold in response to pro-inflammatory cytokines, especially TNF-α and IL-1β. Pantetheine significantly reduced the IAV replication and IAV Matrix 1 (M1) mRNA levels when it was administered prior to and during infection. In addition, cysteamine treatment during IAV infection significantly reduced the viral replication and IAV M1 mRNA levels, whereas pantothenic acid did not. These findings suggest that the metabolic pathway catalyzed by VNN1 pantetheinase plays a suppressive role in IAV infection in the respiratory tract, especially in severe conditions under hypercytokinemia.

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  • Growth hormone activates hepatic and cerebral cholesterol metabolism in small-for-gestational age children without catch-up growth 査読

    Satoshi Hirayama, Hironori Nagasaka, Saori Nakagawa, Mayuko Takuwa, Mariko Nakacho, Tohru Yorifuji, Hiroki Kondou, Hirokazu Tsukahara, Ichiro Morioka, Akihito Ishida, Susumu Yamato, Takashi Miida

    JOURNAL OF CLINICAL LIPIDOLOGY   11 ( 4 )   1032 - 1042   2017年8月

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    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 SCIENCE INC  

    BACKGROUND: Growth hormone (GH) replacement therapy improves hypercholesterolemia in patients with GH deficiency, suggesting that GH modulates cholesterol metabolism.
    OBJECTIVES: We examined GH effects on lipid profiles and cholesterol-related markers reflecting hepatic and cerebral cholesterol metabolism in small-for-gestational age (SGA) children without catchup growth.
    METHODS: This study examined SGA children without catch-up growth (n = 22) and healthy children (controls, n = 11). Based on parents' choice, 11 SGA children received GH at 0.23 to 0.25mg/kg/d for 6 months, and at 0.34 to 0.36 mg/kg/d for the subsequent 6 months (GH (+) group). The other SGA children received no GH (GH (-) group, n = 11). We ascertained baseline and posttreatment lipid profiles and cholesterol-related markers reflecting hepatic and cerebral cholesterol metabolism.
    RESULTS: Baseline lipid profiles of SGA children and controls were similar. Serum 24S-hydroxycholesterol (marker for cerebral cholesterol metabolism) concentration was 19% lower in SGA children than in controls (P &lt; .05). Compared with baseline, the GH (+) group low-density lipoprotein -cholesterol concentration had decreased by 6.6% during 6 months and 8.8% during 12 months (P &lt;.01), whereas the high-density lipoprotein-cholesterol concentration had increased by 1.7% (P =.07) and 3.3% (P &lt; .01). Serum 7a-hydroxycholesterol (marker for hepatic cholesterol elimination) concentration had increased by 34% at 6 months and 35% at 12 months (P &lt; .01). In addition, 24S-hydroxycholesterol increased by 25% and 26% (P &lt; .001). No marker for cholesterol synthesis or absorption changed. The GH (-) group lipid profiles and oxysterols remained unchanged during the observation period.
    CONCLUSION: GH activates hepatic and cerebral cholesterol metabolism in SGA children without catch-up growth. (C) 2017 National Lipid Association. All rights reserved.

    DOI: 10.1016/j.jacl.2017.05.010

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    その他リンク: http://orcid.org/0000-0002-4294-8030

  • New age-based weight estimation formulae for Japanese children. 国際誌

    Nobuyuki Nosaka, Takashi Yorifuji, Emily Knaup, Kohei Tsukahara, Takashi Muguruma, Ayumi Okada, Hirokazu Tsukahara, Hiroyuki Doi

    Pediatrics international : official journal of the Japan Pediatric Society   59 ( 6 )   727 - 732   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Although dosing and sizing of resuscitation drugs and equipment are mostly weight based, time is usually insufficient to weigh critically ill children. Many age-based weight estimation formulae for emergency use have been developed worldwide, but there is no specific formula for Japanese children. The aim of this study was therefore to develop and validate age-based formulae for estimating the bodyweight of children living in Japan. METHODS: A total of 370 980 measurements of bodyweight were obtained from 39 547 participants aged 12-155 months. They participated in a national survey, called the Longitudinal Survey of Babies in the 21st Century, which started in 2001. We created the new original weight estimation formulae for children living in Japan, called the Japanese Pediatric Assessment of Normal weight (JAPAN) formulae, using 75% of measurements that were randomly selected from the total measurements. To check the validity of the formulae, we applied the JAPAN formulae, the Park et al. formula for Korean children, and the commonly used Nelson formula for the remaining 25% of measurements. The mean absolute error and the root mean square error (RMSE) were calculated for each scale. RESULTS: The JAPAN formulae performed better than the two other formulae among Japanese children, with a mean absolute error and RMSE of 0.83 and 1.08 (kg), respectively. The performance of the Park et al. formulae for Korean children was poor for children living in Japan. CONCLUSIONS: The newly developed JAPAN formulae for age-based weight estimation are appropriate for children living in Japan.

    DOI: 10.1111/ped.13259

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  • Intracranial Pressure Monitoring for Pediatric Acute Encephalopathy.

    Nobuyuki Nosaka, Kohei Tsukahara, Emily Knaup, Toshihiko Yabuuchi, Tomonobu Kikkawa, Yosuke Fujii, Masato Yashiro, Takao Yasuhara, Ayumi Okada, Toyomu Ugawa, Atsunori Nakao, Hirokazu Tsukahara, Isao Date

    Acta medica Okayama   71 ( 2 )   179 - 180   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Newly published clinical practice guidelines recommend intracranial pressure (ICP) monitoring in critical care for the management of pediatric acute encephalopathy (pAE), but the utility of ICP monitoring for pAE has been poorly studied. We recently performed direct ICP monitoring for two patients. We observed that although the direct ICP monitoring had clinical benefits with less body weight gain and no vasopressor use in both cases, this monitoring technique is still invasive. Future studies should determine the utility of non-invasive ICP monitoring systems in pAE to further improve the quality of intensive-care management.

    DOI: 10.18926/AMO/54987

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  • Circulating tricarboxylic acid cycle metabolite levels in citrin-deficient children with metabolic adaptation, with and without sodium pyruvate treatment. 査読 国際誌

    Hironori Nagasaka, Haruki Komatsu, Ayano Inui, Mariko Nakacho, Ichiro Morioka, Hirokazu Tsukahara, Shunsaku Kaji, Satoshi Hirayama, Takashi Miida, Hiroki Kondou, Kenji Ihara, Mariko Yagi, Zenro Kizaki, Kazuhiko Bessho, Takahiro Kodama, Kazumoto Iijima, Takeyori Saheki, Tohru Yorifuji, Akira Honda

    Molecular genetics and metabolism   120 ( 3 )   207 - 212   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Citrin deficiency causes adult-onset type II citrullinemia (CTLN-2), which later manifests as severe liver steatosis and life-threatening encephalopathy. Long-standing energy deficit of the liver and brain may predispose ones to CTLN-2. Here, we compared the energy-driving tricarboxylic acid (TCA) cycle and fatty acid beta-oxidation cycle between 22 citrin-deficient children (age, 3-13 years) with normal liver functions and 37 healthy controls (age, 5-13 years). TCA cycle analysis showed that basal plasma citrate and alpha-ketoglutarate levels were significantly higher in the affected than the control group (p &lt; 0.01). Conversely, basal plasma fumarate and malate levels were significantly lower than those for the control (p &lt; 0.001). The plasma level of 3-OH-butyrate derived from fatty acid (3-oxidation was significantly higher in the affected group (p &lt; 0.01). Ten patients underwent sodium pyruvate therapy. However, this therapy did not correct or attenuate such deviations in both cycles. Sodium pyruvate therapy significantly increased fasting insulin secretion (p &lt; 0.01); the fasting sugar level remained unchanged. Our results suggest that citrin-deficient children show considerable deviations of TCA cycle metabolite profiles that are resistant to sodium pyruvate treatment. Thus, long-standing and considerable TCA cycle dysfunction might be a pivotal metabolic background of CTLN-2 development. (C) 2016 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.ymgme.2016.12.011

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  • Pediatric intestinal Behçet disease complicated by myeloid malignancies.

    Kiichiro Kanamitsu, Akira Shimada, Ritsuo Nishiuchi, Tomonari Shigemura, Yozo Nakazawa, Kenichi Koike, Yuichi Kodama, Yuichi Shinkoda, Yoshifumi Kawano, Kozo Yasui, Koji Sasaki, Ryosuke Kajiwara, Hirokazu Tsukahara, Atsushi Manabe

    International journal of hematology   105 ( 3 )   377 - 382   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Behçet disease (BD) is rarely seen in children. Its clinical manifestations are believed to differ between pediatric and adult patients. The characteristics of BD complicated by myelodysplastic syndrome (MDS) are well established for adult patients; however, because only a few cases of pediatric-onset BD complicated by MDS have been reported, its clinical characteristics remain unknown. We here retrospectively review pediatric-onset BD complicated by myeloid malignancies in Japan, having identified five such patients. All patients were female and had gastrointestinal involvements, but lacked both major features of BD, i.e., uveitis and association with HLA-B51. All patients had advanced MDS or acute myeloid leukemia and received chemotherapy followed by hematopoietic stem cell transplantation. These five cases suggest that intestinal BD and myeloid malignancies have one or more pathophysiological mechanisms in common.

    DOI: 10.1007/s12185-016-2127-7

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  • Recurrent apnea in an infant with pertussis due to household transmission. 国際誌

    Motoharu Ochi, Nobuyuki Nosaka, Emily Knaup, Kohei Tsukahara, Tomonobu Kikkawa, Yousuke Fujii, Masato Yashiro, Keiji Sato, Toyomu Ugawa, Ayumi Okada, Hirokazu Tsukahara

    Clinical case reports   5 ( 3 )   241 - 245   2017年3月

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    記述言語:英語  

    Bordetella pertussis causes life-threatening apnea in infants. Lymphocytosis is an important clue for diagnosis and for determining the severity of pertussis. Antibiotics do not shorten or ameliorate the disease and only decrease the risk of transmission. Antepartum maternal immunization is important for preventing pertussis in infants.

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  • Effects of Therapeutic Hypothermia for Neuroprotection from the Viewpoint of Redox Regulation.

    Nobuyuki Nosaka, Ayumi Okada, Hirokazu Tsukahara

    Acta medica Okayama   71 ( 1 )   1 - 9   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Redox regulation has recently been recognized as an important factor in acute illnesses as well as in chronic diseases. It has also become a target for neuroprotection in acute intensive care. Despite its well-known therapeutic effects, therapeutic hypothermia has recently been re-evaluated for its potential use in emergency and critical care medicine. Hypothermia is an undesirable physiological condition that can increase oxidative stress and decrease anti-oxidative potency. However, many studies have shown that under ischemia/reperfusion conditions, therapeutic hypothermia actually suppresses enhanced oxidative stress and maintains or increases anti-oxidative potency. This review provides an overview and outlook for the future of therapeutic hypothermia for neuroprotection from the perspective of redox regulation in patients with post-cardiac arrest syndrome and traumatic brain injury.

    DOI: 10.18926/AMO/54819

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  • Local and Systemic Immune Responses to Influenza A Virus Infection in Pneumonia and Encephalitis Mouse Models. 国際誌

    Yoshiharu Nagaoka, Nobuyuki Nosaka, Mutsuko Yamada, Masato Yashiro, Yosuke Washio, Kenji Baba, Tsuneo Morishima, Hirokazu Tsukahara

    Disease markers   2017   2594231 - 2594231   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: To compare local and systemic profiles between different disease pathologies (pneumonia and encephalitis) induced by influenza A virus (IAV). METHODS: An IAV pneumonia model was created by intranasal inoculation of C57BL/6 mice with influenza A/WSN/33 (H1N1) virus. Lung lavage and blood collection were performed on day 3 after IAV inoculation. Similarly, an IAV encephalitis mouse model was created by direct intracranial IAV inoculation. Cerebrospinal fluid (CSF) and blood collection were conducted according to the same schedule. Cytokine/chemokine profiles were produced for each collected sample. Then the data were compared visually using radar charts. RESULTS: Serum cytokine profiles were similar in pneumonia and encephalitis models, but local responses between the bronchoalveolar lavage fluid (BALF) in the pneumonia model and CSF in the encephalitis model differed. Moreover, to varying degrees, the profiles of local cytokines/chemokines differed from those of serum in both the pneumonia and encephalitis models. CONCLUSION: Investigating local samples such as BALF and CSF is important for evaluating local immune responses, providing insight into pathology at the primary loci of infection. Serum data alone might be insufficient to elucidate local immune responses and might not enable clinicians to devise the most appropriate treatment strategies.

    DOI: 10.1155/2017/2594231

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  • Neonatal-Onset Hereditary Coproporphyria: A New Variant of Hereditary Coproporphyria. 国際誌

    Kosei Hasegawa, Hiroyuki Tanaka, Miho Yamashita, Yousuke Higuchi, Takayuki Miyai, Junko Yoshimoto, Ayumi Okada, Norihiro Suzuki, Keiji Iwatsuki, Hirokazu Tsukahara

    JIMD reports   37   99 - 106   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Genetic mutation of the coproporphyrinogen oxidase (CPOX) gene causes either hereditary coproporphyria (HCP) or harderoporphyria. HCP, a rare hepatic porphyria, causes acute attacks after puberty and rarely accompanies cutaneous symptoms. In contrast, harderoporphyria is an erythropoietic porphyria that represents photosensitivity and hemolytic anemia from the neonatal period. In patients with harderoporphyria, the p.Lys404Glu mutation is found in the homozygous or compound heterozygous state with another mutation, and a marked increase in harderoporphyrin is observed. This report describes a neonate with symptoms of erythropoietic harderoporphyria (photosensitivity of the skin, hemolytic anemia, and jaundice). However, the pattern of porphyrin metabolites of feces was consistent with that of typical HCP, not of harderoporphyria. We found a heterozygous, novel, four-base pair deletion in exon 7 of the CPOX gene, although other mutations including the p.Lys404Glu mutation in CPOX were not found. By unknown etiology, our patient had accompanying adrenocortical insufficiency and 46, XY disorders of sex development. Based on genetic mutation of the CPOX gene and information from a previous similar case report, we consider that neonatal-onset HCP is a variant of HCP.

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  • Urinary Cross-linked N-terminal Telopeptide of Type I Collagen Levels of Infants with Osteogenesis Imperfecta and Healthy Infants.

    Miho Yamashita, Kosei Hasegawa, Yousuke Higuchi, Takayuki Miyai, Ayumi Okada, Hiroyuki Tanaka, Hirokazu Tsukahara

    Acta medica Okayama   70 ( 6 )   435 - 439   2016年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The urinary cross-linked N-terminal telopeptide of type I collagen (uNTx) levels in infantile osteogenesis imperfecta (OI) have not been well studied. Here we investigated the levels of uNTx in infants with OI and healthy infants. We collected spot urine samples from 30 infants with OI (male/female, 14/16; Sillence classification, I/II/III/IV: 15/3/6/6; age, 5.2±4.4 months) and 120 healthy infants (male/female, 75/45; age, 5.1±4.1 months) for the measurement of uNTx levels. The uNTx levels of the OI infants were significantly lower than those of the healthy infants (mean±SD, 1,363.7±530.1 vs. 2,622.2±1,202.6 nmol BCE/mmol Cr; p<0.001). The uNTx levels of the infants with type I OI were significantly lower than those of the age-matched healthy infants, although an overlap was observed between the 2 groups. Among the 1-month-old infants, the uNTx levels of the infants with types I, III or IV OI were significantly lower than those of the healthy infants, without overlap (1,622.5±235.8 vs. 3,781.0±1,027.1 nmol BCE/mmol Cr; p<0.001). These results indicate that uNTx levels are significantly lower in infants with OI than in healthy infants, and they suggest that uNTx might be useful as a reference for diagnosing OI.

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  • Development of a Japanese scale for assessment of paediatric normal weight. 国際誌

    Nobuyuki Nosaka, Takashi Yorifuji, Emily Knaup, Takashi Muguruma, Ayumi Okada, Hirokazu Tsukahara, Hiroyuki Doi

    Resuscitation   105   e11-2   2016年8月

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  • Validity of Mothers' Reports of Children's Weight in Japan.

    Nobuyuki Nosaka, Takeo Fujiwara, Emily Knaup, Ayumi Okada, Hirokazu Tsukahara

    Acta medica Okayama   70 ( 4 )   255 - 9   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Estimation methods for pediatric weight have not been evaluated for Japanese children. This study aimed to assess the accuracy of mothers' reports of their children's weight in Japan. We also evaluated potential alternatives to the estimation of weight, including the Broselow tape (BT), Advanced Pediatric Life Support (APLS), and Park's formulae. We prospectively collected cross-sectional data on a convenience sample of 237 children aged less than 10 years who presented to a general pediatric outpatient clinic with their mothers. Each weight estimation method was evaluated using Bland- Altman plots and by calculating the proportion within 10% and 20% of the measured weight. Mothers' reports of weight were the most accurate method, with 94.9% within 10% of the measured weight, the lowest mean difference (0.27kg), and the shortest 95% limit of agreement (-1.4 to 1.9kg). The BT was the most reliable alternative, followed by APLS and Park's formulae. Mothers' reports of their children 's weight are more accurate than other weight estimation methods. When no report of a child's weight by the mother is available, BT is the best alternative. When an aged-based formula is the only option, the APLS formula is preferred.

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  • Breastfeeding and Risk of Kawasaki Disease: A Nationwide Longitudinal Survey in Japan. 国際誌

    Takashi Yorifuji, Hirokazu Tsukahara, Hiroyuki Doi

    Pediatrics   137 ( 6 )   2016年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND AND OBJECTIVES: Kawasaki disease (KD) is the most common cause of childhood-acquired heart disease in developed countries. However, the etiology of KD is not known. Aberrant immune responses are considered to play key roles in disease initiation and breastfeeding can mature immune system in infants. We thus examined the association between breastfeeding and the development of KD. METHODS: We used a nationwide population-based longitudinal survey ongoing since 2010 and restricted participants to a total of 37 630 children who had data on their feeding during infancy. Infant feeding practice was queried at 6 to 7 months of age, and responses to questions about hospital admission for KD during the period from 6 to 30 months of age were used as outcome. We conducted logistic regression analyses controlling for child and maternal factors with formula feeding without colostrum as our reference group. RESULTS: A total of 232 hospital admissions were observed. Children who were breastfed exclusively or partially were less likely to be hospitalized for KD compared with those who were formula fed without colostrum; odds ratios for hospitalization were 0.26 (95% confidence interval: 0.12-0.55) for exclusive breastfeeding and 0.27 (95% confidence interval: 0.13-0.55) for partial breastfeeding. Although the risk reduction was not statistically significant, feeding colostrum only also provided a protective effect. CONCLUSIONS: We observed protective effects of breastfeeding on the development of KD during the period from 6 to 30 months of age in a nationwide, population-based, longitudinal survey in Japan, the country in which KD is most common.

    DOI: 10.1542/peds.2015-3919

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  • Adults with germline CBL mutation complicated with juvenile myelomonocytic leukemia at infancy. 国際誌

    Michiko Muraoka, Chiho Okuma, Kiichiro Kanamitsu, Hisashi Ishida, Yui Kanazawa, Kana Washio, Masafumi Seki, Motohiro Kato, Junko Takita, Yusuke Sato, Seishi Ogawa, Hirokazu Tsukahara, Megumi Oda, Akira Shimada

    Journal of human genetics   61 ( 6 )   523 - 6   2016年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Juvenile myelomonocytic leukemia (JMML) appears to be a life-threatening disease and showed poor prognosis even after hematopoietic stem cell transplantation (HSCT) because of high relapse rate. On the other hand, recent molecular analysis revealed the heterogeneity of JMML. Here we report that two JMML patients survived >20 years without HSCT and both patients had uniparental disomy of 11q23 where CBL is located without the phenomenon found in neither Noonan syndrome nor Noonan syndrome-like disorder. We think that some JMML patients with CBL mutation might show the good prognosis in later life after remission of JMML.

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  • Letter to the Editor regarding the paper by Sun G et al: Elevated serum levels of neutrophil elastase in patients with influenza virus-associated encephalopathy. J Neuro Sci 2015;349:190-195. 国際誌

    Nobuyuki Nosaka, Kazuki Hatayama, Yousuke Fujii, Masato Yashiro, Hirokazu Tsukahara, Tsuneo Morishima

    Journal of the neurological sciences   364   188 - 188   2016年5月

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  • A novel mutation p.Ser348Cys in FGFR3 causes achondroplasia. 国際誌

    Kosei Hasegawa, Rie Fukuhara, Tadashi Moriwake, Hiroyuki Tanaka, Yousuke Higuchi, Miho Yamashita, Hirokazu Tsukahara

    American journal of medical genetics. Part A   170A ( 5 )   1370 - 2   2016年5月

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    記述言語:英語  

    DOI: 10.1002/ajmg.a.37557

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  • HDR syndrome in a Japanese girl with biliary atresia: a case report. 国際誌

    Yousuke Higuchi, Kosei Hasegawa, Miho Yamashita, Yousuke Fujii, Hiroyuki Tanaka, Hirokazu Tsukahara

    BMC pediatrics   16   14 - 14   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder. We report the first detailed case of hypoparathyroidism complicated by biliary atresia. CASE PRESENTATION: A 1-year-old Japanese girl was admitted to our hospital for living donor liver transplantation. She suffered from obstructive jaundice owing to biliary atresia. She also had persistent hypocalcemia. Despite oral calcium and abundant vitamin D supplementation, a laboratory test showed hypocalcemia (1.4 mmol/l) and hyperphosphatemia (2.6 mmol/l). The intact parathyroid hormone level was normal (66 ng/l) with severe vitamin D deficiency (25-hydroxy vitamin D: undetectable levels). There were no rachitic changes in metaphysis on X-rays. Her family history showed that her mother had sensorineural deafness, a low serum calcium level (2.1 mmol/l), hypoplastic left kidney, and a past history of an operation for right vesicoureteral reflux. We suspected that this patient and her mother have hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome. A heterozygous GATA3 gene mutation (c.736delGinsAT) was found in this patient and her mother, but not in her father. CONCLUSION: This familial case confirms the importance of family history in the diagnosis of HDR syndrome. Regardless of marked vitamin D deficiency, the complication of hypoparathyroidism prevented the onset of vitamin D deficiency rickets in our patient.

    DOI: 10.1186/s12887-016-0550-9

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  • Evaluation of rapid immunochromatographic tests for norovirus in neonatal and infant faecal specimens. 国際誌

    Nobumasa Takahashi, Ikuko Nojima, Tooru Araki, Mizue Takasugi, Tomoko Sakane, Aya Kodera, Masanori Ikeda, Hirokazu Tsukahara

    The Journal of international medical research   43 ( 5 )   648 - 52   2015年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: To compare the diagnostic performance of two norovirus rapid immunochromatographic kits (QuickNavi(®)-Norovirus [QN] and QuickNavi®-Norovirus 2 [QN2]; Denka Seiken, Niigata, Japan) for neonatal and infant faecal specimens. METHODS: Monthly faecal samples were collected from infants from birth to 12 months of age, and tested for norovirus using QN and QN2. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used as the gold standard for norovirus detection. The diagnostic performance of the kits was calculated. RESULTS: A total of 343 specimens from 81 infants were analysed. In all samples, the specificity of QN and QN2 was 80% (275/343) and 99% (339/343), respectively. In infants aged <1 month, the specificity of QN was 33% (23/70), increasing to 93% at 4 months of age. Specificity of QN2 was ≥94% in infants between 0 and 12 months of age. CONCLUSIONS: QN2 offers improved performance and is more useful than QN for the diagnosis of norovirus infection in the neonatal and infant period.

    DOI: 10.1177/0300060515592902

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  • Anti-high mobility group box-1 monoclonal antibody treatment provides protection against influenza A virus (H1N1)-induced pneumonia in mice. 国際誌

    Nobuyuki Nosaka, Masato Yashiro, Mutsuko Yamada, Yosuke Fujii, Hirokazu Tsukahara, Keyue Liu, Masahiro Nishibori, Akihiro Matsukawa, Tsuneo Morishima

    Critical care (London, England)   19   249 - 249   2015年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: Provision for the emergence of an influenza pandemic is an urgent issue. The discovery of a novel anti-influenza therapeutic approach would increase the effectiveness of traditional virus-based strategies. This study was undertaken to evaluate the therapeutic effects of anti-high mobility group box-1 (HMGB1) monoclonal antibody (mAb) treatment on influenza A virus (H1N1)-induced pneumonia in mice. METHODS: Nine-week-old male C57BL/6 mice were inoculated with H1N1, then anti-HMGB1 mAb or control mAb were administered intravenously at 1, 24 and 48 hours after H1N1 inoculation and the survival rate was analyzed. Lung lavage and histopathological analysis were performed on days 3, 5, 7 and 10 after inoculation. RESULTS: Anti-HMGB1 mAb significantly improved the survival rate of H1N1-inoculated mice (1 out of 15 versus 8 out of 15 deaths in the anti-HMGB1 mAb-treated group versus the control mAb-treated group, p < 0.01), although the treatment did not affect virus propagation in the lungs. The treatment also significantly attenuated histological changes and neutrophil infiltration in the lungs of H1N1-inoculated mice. This was associated with inhibition of HMGB1 and suppression of inflammatory cytokine/chemokine expression and oxidative stress enhancement, which were observed in H1N1-inoculated mice. The expression of receptor for advanced glycation end products and nuclear factor κB was attenuated by the treatment. CONCLUSIONS: Anti-HMGB1 mAb may provide a novel and effective pharmacological strategy for severe influenza virus infection in humans by reducing the inflammatory responses induced by HMGB1.

    DOI: 10.1186/s13054-015-0983-9

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  • Inhibitory Effects of Edaravone, a Free Radical Scavenger, on Cytokine-induced Hyperpermeability of Human Pulmonary Microvascular Endothelial Cells:A Comparison with Dexamethasone and Nitric Oxide Synthase Inhibitor.

    Yukie Saito, Yousuke Fujii, Masato Yashiro, Mitsuru Tsuge, Nobuyuki Nosaka, Nobuko Yamashita, Mutsuko Yamada, Hirokazu Tsukahara, Tsuneo Morishima

    Acta medica Okayama   69 ( 5 )   279 - 90   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Lung hyperpermeability affects the development of acute respiratory distress syndrome (ARDS), but therapeutic strategies for the control of microvascular permeability have not been established. We examined the effects of edaravone, dexamethasone, and N-monomethyl-L-arginine (L-NMMA) on permeability changes in human pulmonary microvascular endothelial cells (PMVEC) under a hypercytokinemic state. Human PMVEC were seeded in a Boyden chamber. After monolayer confluence was achieved, the culture media were replaced respectively by culture media containing edaravone, dexamethasone, and L-NMMA. After 24-h incubation, the monolayer was stimulated with tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Fluorescein-labeled dextran was added. Then the trans-human PMVEC leak was measured. Expressions of vascular endothelial-cadherin (VE-cadherin) and zonula occludens-1 protein (ZO-1) were evaluated using real-time quantitative polymerase chain reaction and immunofluorescence microscopy. The results showed that TNF-α+IL-1β markedly increased pulmonary microvascular permeability. Pretreatment with edaravone, dexamethasone, or L-NMMA attenuated the hyperpermeability and inhibited the cytokine-induced reduction of VE-cadherin expression on immunofluorescence staining. Edaravone and dexamethasone increased the expression of ZO-1 at both the mRNA and protein levels. Edaravone and dexamethasone inhibited the permeability changes of human PMVEC, at least partly through an enhancement of VE-cadherin. Collectively, these results suggest a potential therapeutic approach for intervention in patients with ARDS.

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  • Changes of lipoproteins in phenylalanine hydroxylase-deficient children during the first year of life. 査読 国際誌

    Hironori Nagasaka, Hirokazu Tsukahara, Yoshiyuki Okano, Ken-ichi Hirano, Toshihiro Sakurai, Shu-Ping Hui, Toshihiro Ohura, Hiromi Usui, Tohru Yorifuji, Satoshi Hirayama, Akira Ohtake, Takashi Miida

    Clinica chimica acta; international journal of clinical chemistry   433   1 - 4   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Influence of hyperphenylalaninemia on lipoproteins in early life remains unclear. METHODS: We enrolled 24 phenylalanine hydroxylase (PAH)-deficient children who were classified into a phenylketonuria (PKU) group (n=12) lacking PAH activity and a benign hyperphenylalaninemia (HPA) group (n=12) having partial PAH activity, and their 11 non-affected siblings. We measured serum total-cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol levels together with apolipoproteins for the first year of life, and compared them with those of 30 age-matched healthy controls. RESULTS: The affected groups invariably had lower cholesterol levels than non-affected groups. At birth, HDL-cholesterol decrease was greatest and predominated over the LDL-cholesterol decrease: total cholesterol, 28/36% decrease to the control level in HPA/PKU; HDL-cholesterol, 33/51%; LDL-cholesterol, 20/28%. At 3months, the opposite changes were observed: total cholesterol, 16/28%; HDL-cholesterol, 13/23%; LDL-cholesterol, 16/33%. At 12months, LDL were still significantly lower in both groups (8/18%, p<.05 and .001), although HDL was significantly decreased only in the PKU group (15%, p<.05). Apolipoprotein A-I/A-II and B changed respectively in accordance with HDL-cholesterol and LDL-cholesterol changes. Despite similar phenylalanine levels, the PKU group invariably had lower cholesterol concentrations than the HPA group had. CONCLUSION: Irrespective of phenylalanine concentrations, lipoprotein synthesis in PAH-deficient children, particularly in PKU children, was suppressed in early life.

    DOI: 10.1016/j.cca.2014.02.020

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  • Gene expression analysis in children with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. 国際誌

    Mitsuru Tsuge, Takashi Oka, Nobuko Yamashita, Yukie Saito, Yosuke Fujii, Yoshiharu Nagaoka, Masato Yashiro, Hirokazu Tsukahara, Tsuneo Morishima

    Journal of neurovirology   20 ( 1 )   73 - 84   2014年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Viral infections have been implicated as a cause of complex seizures in children. The pathogenic differences in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis remain unclear. This study analyzed the gene expression profiles in the peripheral whole blood from pediatric patients with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. The gene expression profiles of ten patients (five with seizures and five without) with influenza A(H1N1)pdm09 and six patients (three with seizures and three without) with rotavirus gastroenteritis were examined. Gene expression profiles in the whole blood were different in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. Transcripts related to the immune response were significantly differentially expressed in complex seizures with influenza A(H1N1)pdm09, and transcripts related to the stress response were significantly differentially expressed in complex seizures with rotavirus gastroenteritis. Pathway analysis showed that the mitogen-activated protein kinases in the T cell receptor signaling pathway were activated in complex seizures due to influenza A(H1N1)pdm09. Dysregulation of the genes related to immune response or stress response could contribute to the pathogenic differences of the complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis.

    DOI: 10.1007/s13365-013-0231-5

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  • 気管支肺異形成症の早期予測におけるカルボキシヘモグロビンの有用性

    徳力 周子, 奥野 貴士, 巨田 元礼, 大嶋 勇成, 塚原 宏一

    日本未熟児新生児学会雑誌   25 ( 3 )   470 - 470   2013年11月

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    記述言語:日本語   出版者・発行元:(公社)日本新生児成育医学会  

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  • Pathogenic mechanisms of influenza A(H1N1)pdm09 infection elucidated on gene expression profiling. 国際誌

    Nobuko Yamashita, Hirokazu Tsukahara, Mitsuru Tsuge, Yoshiharu Nagaoka, Masato Yashiro, Yukie Saito, Yosuke Fujii, Takashi Oka, Tsuneo Morishima

    Pediatrics international : official journal of the Japan Pediatric Society   55 ( 5 )   572 - 7   2013年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The pathogenic mechanisms underlying influenza A(H1N1)pdm09-associated central nervous system (CNS) manifestations and pneumonia remain unclear. This study examined A(H1N1)pdm09 host responses using gene expression profiles of patients' peripheral blood. METHODS: Sixteen A(H1N1)pdm09-infected children in three groups were examined: a CNS group, with convulsion and altered consciousness (n = 6); a pneumonia (Pneu) group (n = 5); and a group of infected control patients (n = 5). The signal ratios of the acute to recovery phases in CNS or Pneu were analyzed versus those of the control. RESULTS: The CNS (619 transcripts) and Pneu (656 transcripts) groups had significantly increased signal ratios compared to the control group. Regarding the increased ratios of transcripts shown by multiple probes, contactin-associated protein-like 3 transcripts, oleoyl-ACP hydrolase transcripts, and interleukin 1 type 1 receptor were observed in CNS and Pneu. Increased ratios of prostaglandin-endoperoxide synthase 2 and α-synuclein were characteristic of CNS. Alkaline phosphatase and the Fc fragment of IgA receptor were characteristic of Pneu. Regarding enriched gene ontology terms, 'response to lipopolysaccharide', 'innate immune response', and 'intrinsic to membrane' were observed commonly in CNS and Pneu. Enriched gene ontology terms related to 'hemoglobin' and 'hemostasis' were, respectively, characteristic of CNS and Pneu. CONCLUSION: These symptom-associated transcripts might be some clues to the pathogenesis of the A(H1N1)pdm09 infection.

    DOI: 10.1111/ped.12139

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  • Prognostic value of brain injury biomarkers in acute encephalitis/encephalopathy. 国際誌

    Hirokazu Tsukahara, Yosuke Fujii, Kousaku Matsubara, Mutsuko Yamada, Yoshiharu Nagaoka, Yukie Saito, Masato Yashiro, Mitsuru Tsuge, Shinichiro Goto, Tetsuro Kitamura, Atsuko Hata, Takashi Ichiyama, Tsuneo Morishima

    Pediatrics international : official journal of the Japan Pediatric Society   55 ( 4 )   461 - 4   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Acute encephalitis/encephalopathy (AEE) is a devastating cause of severe neurodevelopmental sequelae or death in children. Assessing ongoing brain injury and predicting outcomes using bedside point-of-care testing is expected to be extremely valuable. METHODS: For this study, three brain injury markers, S-100B, glial fibrillary acidic protein (GFAP), and tau protein, were measured in early cerebrospinal fluid samples of children with AEE. Subjects comprised three groups: Group 1 (non-AEE control, n = 27); Group 2 (AEE with normal resolution or mild sequelae, n = 13); and Group 3 (AEE with severe sequelae or death, i.e. "poor outcome," n = 10). RESULTS: All marker levels were significantly higher in Group 3 than in Group 1 or 2. In Group 3, only S-100B was significantly higher in non-survivors than in survivors. For scoring assessment (range: 0-3 points), the predictive accuracies of 3 points for poor outcomes in children with AEE (i.e. Group 2 and 3, n = 23) were 91% (21/23) for S-100B, 74% (17/23) for GFAP, and 78% (18/23) for tau. When the scores were summed up for S-100B, GFAP, and tau (range: 0-9 points), and for S-100B and tau (range: 0-6 points), the patients with poor outcomes were identified more accurately using the respective thresholds of 6 points and 4 points (96% [22/23] and 100% [23/23], respectively). CONCLUSION: Our findings suggest that combined measurement and scoring assessment of the markers, especially S-100B and tau, show promise as predictors of clinical outcomes in children with AEE.

    DOI: 10.1111/ped.12094

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  • 広汎性発達障害、注意欠陥/多動性障害と酸化ストレスマーカーの関連性に関する検討

    川谷 正男, 巨田 元礼, 米谷 博, 大嶋 勇成, 平谷 美智夫, 友田 明美, 塚原 宏一

    脳と発達   45 ( Suppl. )   S339 - S339   2013年5月

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    記述言語:日本語   出版者・発行元:(一社)日本小児神経学会  

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  • Metabolic improvements in intrahepatic porto-systemic venous shunt presenting various metabolic abnormalities by 4-phenylacetate 査読

    Nagasaka H, Miida T, Yorifuji T, Hirano K.-I, Inui A, Fujisawa T, Tsukahara H, Hayashi H, Inomata Y

    Clin Chim Acta   419   52 - 56   2013年4月

  • Oxysterol changes along with cholesterol and vitamin D changes in adult phenylketonuric patients diagnosed by newborn mass-screening. 査読

    Nagasaka H, Okano Y, Kimura A, Mizuochi T, Sanayama Y, Takatani T, Nakagawa S, Hasegawa E, Hirano K, Mochizuki H, Ohura T, Ishige-Wada M, Usui H, Yorifuji T, Tsukahara H, Hirayama S, Ohtake A, Yamato S, Miida T

    Clinica chimica acta; international journal of clinical chemistry   416   54 - 59   2013年2月

  • Sustained high plasma mannose less sensitive to fluctuating blood glucose in glycogen storage disease type Ia children 査読

    Nagasaka H, Yorifuji T, Bandsma R.H.J, Takatani T, Asano H, Mochizuki H, Takuwa M, Tsukahara H, Inui A, Tsunoda T, Komatsu H, Hiejima E, Fujisawa T, Hirano K.-I, Miida T, Ohtake A, Taguchi T, Miwa I

    J Inherit Metab Dis   36 ( 1 )   75 - 81   2013年1月

  • Thioredoxin-1 and oxidative stress status in pregnant women at early third trimester of pregnancy: relation to maternal and neonatal characteristics.

    Yoko Nakatsukasa, Hirokazu Tsukahara, Kazuhisa Tabuchi, Masako Tabuchi, Tomoko Magami, Mutsuko Yamada, Yosuke Fujii, Masato Yashiro, Mitsuru Tsuge, Tsuneo Morishima

    Journal of clinical biochemistry and nutrition   52 ( 1 )   27 - 31   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This study examined the clinical and biological importance of thioredoxin-1, a redox-active defensive protein that controls multiple biological functions, in pregnant women. We measured serum concentrations of thioredoxin-1, total hydroperoxides, and redox potential in 60 pregnant women at the early third trimester: gestational age of 27-29 weeks. The thioredoxin-1 concentration (mean ± SD) was 90 ± 42 ng/ml. Total hydroperoxides was 471 ± 105 U.CARR (1 U.CARR = 0.08 mg/dl H(2)O(2)). Redox potential was 2142 ± 273 µmol/l. The total hydroperoxides: redox potential ratio (oxidative stress index) was 0.23 ± 0.08. Thioredoxin-1, total hydroperoxides, and oxidative stress index were higher and redox potential was lower than in blood of healthy adults. Total hydroperoxides and redox potential were mutually correlated significantly and negatively. Thioredoxin-1 correlated significantly and negatively and redox potential correlated significantly and positively with body weight and body mass index. Thioredoxin-1 and redox potential correlated significantly and positively with uric acid and albumin, respectively. Thioredoxin-1 and oxidative stress index correlated significantly and negatively and redox potential significantly and positively with neonatal birth weight. These results suggest that high concentrations of thioredoxin-1 are linked to high oxidative stress status in pregnant women and that neonatal birth weight is affected by the maternal oxidative condition during later pregnancy.

    DOI: 10.3164/jcbn.12-71

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  • Redox-active protein thioredoxin-1 administration ameliorates influenza A virus (H1N1)-induced acute lung injury in mice. 国際誌

    Masato Yashiro, Hirokazu Tsukahara, Akihiro Matsukawa, Mutsuko Yamada, Yosuke Fujii, Yoshiharu Nagaoka, Mitsuru Tsuge, Nobuko Yamashita, Toshihiro Ito, Masao Yamada, Hiroshi Masutani, Junji Yodoi, Tsuneo Morishima

    Critical care medicine   41 ( 1 )   171 - 81   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: Influenza virus infections can cause severe acute lung injury leading to significant morbidity and mortality. Thioredoxin-1 is a redox-active defensive protein induced in response to stress conditions. Animal experiments have revealed that thioredoxin-1 has protective effects against various severe disorders. This study was undertaken to evaluate the protective effects of recombinant human thioredoxin-1 administration on influenza A virus (H1N1)-induced acute lung injury in mice. DESIGN: Prospective animal trial. SETTING: Research laboratory. SUBJECTS: Nine-week-old male C57BL/6 mice inoculated with H1N1. INTERVENTION: The mice were divided into a vehicle-treated group and recombinant human thioredoxin-1-treated group. For survival rate analysis, the vehicle or recombinant human thioredoxin-1 was administered intraperitoneally every second day from day -1 to day 13. For lung lavage and pathological analyses, vehicle or recombinant human thioredoxin-1 was administered intraperitoneally on days -1, 1, and 3. MEASUREMENTS AND MAIN RESULTS: Lung lavage and pathological analyses were performed at 24, 72, and 120 hrs after inoculation. The recombinant human thioredoxin-1 treatment significantly improved the survival rate of H1N1-inoculated mice, although the treatment did not affect virus propagation in the lung. The treatment significantly attenuated the histological changes and neutrophil infiltration in the lung of H1N1-inoculated mice. The treatment significantly attenuated the production of tumor necrosis factor-α and chemokine (C-X-C motif) ligand 1 in the lung and oxidative stress enhancement, which were observed in H1N1-inoculated mice. H1N1 induced expressions of tumor necrosis factor-α and chemokine (C-X-C motif) ligand 1 in murine lung epithelial cells MLE-12, which were inhibited by the addition of recombinant human thioredoxin-1. The recombinant human thioredoxin-1 treatment started 30 mins after H1N1 inoculation also significantly improved the survival of the mice. CONCLUSIONS: Exogenous administration of recombinant human thioredoxin-1 significantly improved the survival rate and attenuated lung histological changes in the murine model of influenza pneumonia. The protective mechanism of thioredoxin-1 might be explained by its potent antioxidative and anti-inflammatory actions. Consequently, recombinant human thioredoxin-1 might be a possible pharmacological strategy for severe influenza virus infection in humans.

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  • Characteristics of NO cycle coupling with urea cycle in non-hyperammonemic carriers of ornithine transcarbamylase deficiency 査読

    H. Nagasaka, T. Yorifuji, H. Egawa, A. Inui, T. Fujisawa, H. Komatsu, H. Tsukahara, S. Uemoto, Y. Inomata

    Molecular Genetics and Metabolism   109 ( 3 )   251 - 254   2013年

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    記述言語:英語  

    DOI: 10.1016/j.ymgme.2013.04.013

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  • Fatty liver and anti-oxidant enzyme activities along with peroxisome proliferator-activated receptors γ and α expressions in the liver of Wilson's disease 査読

    Nagasaka H, Miida T, Inui A, Inoue I, Tsukahara H, Komatsu H, Hiejima E, Fujisawa T, Yorifuji T, Hiranao K.-I, Okajima H, Inomata Y

    Mol Genet Metab   107 ( 3 )   542 - 547   2012年11月

  • Activation of Akt is associated with poor prognosis and chemotherapeutic resistance in pediatric B-precursor acute lymphoblastic leukemia. 査読 国際誌

    Naoto Morishita, Hirokazu Tsukahara, Kosuke Chayama, Toshiaki Ishida, Kana Washio, Takako Miyamura, Nobuko Yamashita, Megumi Oda, Tsuneo Morishima

    Pediatric blood & cancer   59 ( 1 )   83 - 9   2012年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway, a pro-survival pathway, plays important roles in tumor cell growth. However, the role of Akt in the pathogenesis of pediatric B-precursor acute lymphoblastic leukemia (B-pre ALL) remains to be clarified. This study was undertaken to explore the clinical relevance and molecular mechanisms underlying the activation of Akt (i.e., phosphorylated Akt, P-Akt) in pediatric B-pre ALL. Procedure: We evaluated the activation status of Akt in bone marrow samples from 21 children with newly diagnosed B-pre ALL and correlated the expression level of P-Akt with clinicopathologic and prognostic features. Additionally, we transfected the myristoylated Akt cDNA into the B-pre ALL cell line, Nalm-6, and examined the effect, in vitro, of Akt activation on the response to antitumor drugs. Results: P-Akt expression in B-pre ALL blast cells at diagnosis was associated significantly with poor response to induction chemotherapy including prednisolone, dexamethasone, vincristine, and adriamycin in B-pre ALL patients. Both overall survival and relapse-free survival in patients with P-Akt expression were reduced significantly more than in patients without P-Akt expression. Activation of Akt reduced the extent of apoptosis induced by the antitumor drugs in Nalm-6 listed above. Activation of Akt did not induce expression of P-glycoprotein, a drug transporter that is capable of conferring multidrug resistance. Conclusion: These results support the contention that Akt activation is a mechanism of chemotherapeutic resistance in B-pre ALL and suggest that Akt can be a therapeutic target for the treatment of relapsed or refractory pediatric B-pre ALL. © 2011 Wiley Periodicals, Inc.

    DOI: 10.1002/pbc.24034

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  • Oxidative stress biomarkers in pediatric medicine - A 2013 update 査読

    Hirokazu Tsukahara

    Systems Biology of Free Radicals and Antioxidants   689 - 715   2012年5月

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    記述言語:英語   掲載種別:論文集(書籍)内論文   出版者・発行元:Springer-Verlag Berlin Heidelberg  

    A large body of circumstantial evidence emphasizes the critical role of reactive oxygen species (ROS), including superoxide anion and nitric oxide (NO), in acute and chronic pediatric diseases. About 15 years ago, measurement of oxidative damage affecting tissues and organs using specific biomarkers was introduced into the field of pediatric medicine. This chapter is intended to describe recent progress in clinical application of oxidative stress biomarkers in pediatric medicine. First, this chapter briefly presents the biochemistry and pathophysiology of ROS and antioxidative defense systems. Second, it discusses the interrelationship of endothelial dysfunction, NO system blockade, and oxidative stress. Third, it presents a list of clinically applicable biomarkers, along with pediatric diseases in which enhanced oxidative stress might be involved. The discussion emphasizes that many good biomarkers are readily measurable using enzyme-linked immunosorbent assay. Fourth, this chapter presents age-related reference normal ranges of oxidative stress biomarkers, including urinary acrolein-lysine, 8-hydroxy-2′-deoxyguanosine, nitrite/nitrate, and pentosidine. Furthermore, our new and interesting data related to oxidative stress and antioxidative defenses in congenital metabolic disorders, such as Wilson disease, urea cycle defects, citrin deficiency, and phenylketonuria, are presented. Rapid diagnostic tests for measuring blood levels of total hydroperoxides and biological antioxidative potential and urinary levels of 8-hydroxy-2′-deoxyguanosine are also explained. Finally, this chapter describes recent clinical studies that have evaluated the efficacy of antioxidative intervention for oxidative-stress-related diseases. Repeated measurement of multiple appropriate parameters will enable us to discern the pathophysiological patterns of pediatric diseases and guide our therapies appropriately.

    DOI: 10.1007/978-3-642-30018-9_36

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  • Focal EEG abnormalities might reflect neuropathological characteristics of pervasive developmental disorder and attention-deficit/hyperactivity disorder

    Kawatani M, Hiratani M, Kometani H, Nakai A, Tsukahara H, Tomoda A, Mayumi M, Ohshima Y

    Brain & Development   34 ( 9 )   723 - 730   2012年

  • Cross-sectional study of bone metabolism with nutrition in adult classical phenylketonuric patients diagnosed by neonatal screening 査読

    Hironori Nagasaka, Hirokazu Tsukahara, Tomozumi Takatani, Yoshitami Sanayama, Masaki Takayanagi, Toshihiro Ohura, Osamu Sakamoto, Tetsuya Ito, Mika Wada, Makoto Yoshino, Akira Ohtake, Tohru Yorifuji, Satoshi Hirayama, Takashi Miida, Hiroki Fujimoto, Hiroshi Mochizuki, Toshikazu Hattori, Yoshiyuki Okano

    JOURNAL OF BONE AND MINERAL METABOLISM   29 ( 6 )   737 - 743   2011年11月

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    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 JAPAN KK  

    The mechanism underlying the development of osteopenia or osteoporosis in longstanding phenylketonuria (PKU) remains to be clarified. We investigated the details of bone metabolism in 21 female and 13 male classical PKU patients aged 20-35 years. Vitamin D (VD), parathyroid hormone (PTH), bone turnover markers, and daily nutrient intake were examined. The patients had lower daily energy and protein intake than did the age-matched controls (22 women, 14 men), but their respective fat, VD, and calcium intake did not differ. Serum 1,25-dihydroxy VD and 25-hydroxy VD levels in female and male patient groups were significantly higher and lower than those in respective control groups (females, P &lt; 0.001; males, P &lt; 0.05 and P &lt; 0.01, respectively). Serum intact PTH levels were significantly higher in the female patient group (P &lt; 0.05). Urinary calcium levels in the patient groups were significantly higher than those of the control subjects (females, P &lt; 0.001; males, P &lt; 0.05). Bone resorption markers were significantly higher in patients than in controls, although bone formation markers were not different. Patient serum levels of osteoprotegerin-inhibiting bone resorption were significantly lower (females, P &lt; 0.001; males, P &lt; 0.01). None of the bone parameters correlated significantly with serum phenylalanine or nutrient intake. PKU patients exhibited lower VD status and more rapid bone resorption despite normal calcium-VD intakes.

    DOI: 10.1007/s00774-011-0276-6

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  • Experimental evidence that phenylalanine is strongly associated to oxidative stress in adolescents and adults with phenylketonuria 査読

    Yoshitami Sanayama, Hironori Nagasaka, Masaki Takayanagi, Toshihiro Ohura, Osamu Sakamoto, Tetsuya Ito, Mika Ishige-Wada, Hiromi Usui, Makoto Yoshino, Akira Ohtake, Tohru Yorifuji, Hirokazu Tsukahara, Satoshi Hirayama, Takashi Miida, Mitsuru Fukui, Yoshiyuki Okano

    MOLECULAR GENETICS AND METABOLISM   103 ( 3 )   220 - 225   2011年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Few studies have looked at optimal or acceptable serum phenylalanine levels in later life in patients with phenylketonuria (PKU). This study examined the oxidative stress status of adolescents and adults with PKU. Forty PKU patients aged over fifteen years were enrolled, and were compared with thirty age-matched controls. Oxidative stress markers, anti-oxidant enzyme activities in erythrocytes, and blood anti-oxidant levels were examined. Nitric oxide (NO) production was also examined as a measure of oxidative stress. Plasma thiobarbituric acid reactive species and serum malondialdehyde-modified LDL levels were significantly higher in PKU patients than control subjects, and correlated significantly with serum phenylalanine level (P&lt;0.01). Plasma total anti-oxidant reactivity levels were significantly lower in the patient group, and correlated negatively with phenylalanine level (P&lt;0.001). Erythrocyte superoxide dismutase and catalase activities were higher and correlated significantly with phenylalanine level (P&lt;0.01). Glutathione peroxidase activity was lower and correlated negatively with phenylalanine level (P&lt;0.001). The oxidative stress score calculated from these six parameters was significantly higher in patients with serum phenylalanine of 700-800 mu mol/l. Plasma anti-oxidant substances, beta-carotene, and coenzyme Q(10) were also lower (P&lt;0.001), although the decreases did not correlate significantly with the phenylalanine level. Serum nitrite/nitrate levels, as stable NO products, were higher together with low serum asymmetric dimethylarginine, as an endogenous NO inhibitor. Oxidative stress status is closely linked with serum phenylalanine levels. Phenylalanine level in should be maintained PKU below 700-800 mu mol/l even in adult patients. (C) 2011 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.ymgme.2011.03.019

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  • CD36 deficiency predisposing young children to hypoglycemia. 査読

    Nagasaka H, Yorifuji T, Okano Y, Tsukahara H, Yanai H, Hirano K, Hui SP, Hirayama S, Chiba H, Miida T

    Metabolism.   60 ( 6 )   881 - 887   2011年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.metabol.2010.08.008

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  • A case of intracranial saccular aneurysm after primary varicella zoster virus infection. 査読

    Kawatani M, Nakai A, Okuno T, Tsukahara H, Ohshima Y, Mayumi M

    Brain & development   34 ( 1 )   80 - 82   2011年3月

  • Images in emergency medicine. Pregnant woman with gastric pain. Hypertriglyceridemia-induced pancreatitis. 査読

    Nishijima K, Takahashi J, Yamamoto M, Orisaka M, Suzuki C, Tsukahara H, Shukunami K, Kurokawa T, Yoshida Y, Kotsuji F

    Annals of emergency medicine   55 ( 5 )   483, 490   2010年5月

  • Meatus tightly covered by the prepuce is associated with urinary infection 査読

    M Hiraoka, H Tsukahara, Y Ohshima, M Mayumi

    PEDIATRICS INTERNATIONAL   44 ( 6 )   658 - 662   2002年12月

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    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 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&lt;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 査読

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

    NEPHRON   92 ( 2 )   449 - 451   2002年10月

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    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  

    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. 国際誌

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

    Nephron   92 ( 2 )   449 - 51   2002年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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

    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年6月

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    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 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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  • 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年6月

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    記述言語:日本語   出版者・発行元:(一社)日本小児腎臓病学会  

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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年6月

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    記述言語:日本語   出版者・発行元:(一社)日本小児腎臓病学会  

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  • Renal aplasia is the predominant cause of congenital solitary kidneys 査読

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

    KIDNEY INTERNATIONAL   61 ( 5 )   1840 - 1844   2002年5月

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    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 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年9月

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    記述言語:日本語   出版者・発行元:(一社)日本小児アレルギー学会  

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

    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年8月

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

    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年8月

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    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  

    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 &lt; 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 査読

    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年6月

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    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 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 査読

    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年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元: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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  • No evidence for AT2R gene derangement in human urinary tract anomalies 査読

    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年4月

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    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 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年3月

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    記述言語:日本語   出版者・発行元:(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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  • 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年

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    掲載種別:研究論文(学術雑誌)  

    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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  • 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 査読

    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年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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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年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児アレルギー学会  

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  • 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年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児アレルギー学会  

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  • Older boys benefit from higher initial prednisolone therapy for nephrotic syndrome 査読

    M Hiraoka, H Tsukahara, S Haruki, S Hayashi, N Takeda, K Miyagawa, K Okuhara, F Suehiro, Y Ohshima, M Mayumi

    KIDNEY INTERNATIONAL   58 ( 3 )   1247 - 1252   2000年9月

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    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  

    Background A long course of the initial prednisolone therapy has been shown to be more effective than standard-course therapy in reducing relapse rates in children with idiopathic nephrotic syndrome, but it is commonly accompanied by corticosteroid toxicities. There has been no study on prednisolone dosage for the effective treatment of nephrotic syndrome.
    Methods. Sixty-eight children (42 boys and 26 girls) with an initial attack of nephrotic syndrome were randomly allocated into two different long-course treatment groups. Patients in Group 1 received a daily prednisolone dose of 60 mg/m(2) for six weeks, followed by an alternate-day dose of 40 mg/m(2) for six weeks. Patients in Group 2 had a daily dose of 40 mg/m(2) instead of 60 mg/m(2).
    Results. Four children in each group did not respond within six weeks. Group 1 was associated with a significantly earlier response but more frequent corticosteroid toxicities than Group 2. Boys in Group 1 had a higher rate of sustained remission than boys in Group 2 (P = 0.0073), especially boys four years old or more (P = 0.0027), but girls did not show a significant difference (P = 0.863). Boys four years old or more in Group 1 had a course of frequent relapsing less often than those in Group 2 (2 of 13 vs. 6 of 8, P = 0.0075).
    Conclusion. These findings indicate that efficient prednisolone doses may vary between sexes and ages, and that a higher initial prednisolone therapy may be of greater benefit to older boys.

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  • Efficacy of long-term azathioprine for relapsing nephrotic syndrome 査読

    M Hiraoka, H Tsukahara, C Hori, Y Ohshima, T Momoi, A Seo, M Mayumi

    PEDIATRIC NEPHROLOGY   14 ( 8-9 )   776 - 778   2000年8月

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    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  

    Seven patients who had an initial attack of nephrotic syndrome in childhood and had frequent relapses even after cyclophosphamide therapy were given a 2-year course of azathioprine. The mean annual relapse rates decreased from 2.4 +/- 0.5 in the year preceding azathioprine to 0.4 +/- 0.8 in the 1st and 2nd years after its initiation. All six patients who were observed for more than 6 months after discontinuation of the therapy were relapse free for this period. Average doses of prednisolone could also be decreased in the 2nd and subsequent years after the therapy. There were no significant toxic effects. Long-term azathioprine therapy may be well tolerated and effective for nephrotic patients with frequent relapses.

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  • インフルエンザ菌による敗血症性髄膜炎に伴い急性腎不全をきたした3歳女児例

    西村 光敏, 塚原 宏一, 平岡 政弘, 木村 宏輝, 大嶋 勇成, 谷澤 昭彦, 木川 芳春, 眞弓 光文

    日本小児腎不全学会雑誌   20   166 - 168   2000年8月

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    記述言語:日本語   出版者・発行元:日本小児腎不全学会  

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  • 早期ステロイド補充療法

    塚原 宏一

    日本小児呼吸器疾患学会雑誌 = Japanese journal of pediatric pulmonology   11 ( 1 )   55 - 55   2000年6月

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    記述言語:日本語   出版者・発行元:日本小児呼吸器疾患学会  

    DOI: 10.5701/jjpp.11.55

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  • Methylenetetrahydrofolate reductase polymorphism in Kawasaki disease 査読

    H Tsukahara, M Hiraoka, M Saito, K Nishida, R Kobata, S Tsuchida, M Toyooka, H Kimura, F Gejyo, M Mayumi

    PEDIATRICS INTERNATIONAL   42 ( 3 )   236 - 240   2000年6月

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    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 SCIENCE ASIA  

    Background: A genetic aberration in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (677 C to T substitution) has been shown to result in reduced enzyme activity. The hypothesis tested in the present study was that a higher proportion of Kawasaki disease (KD) patients with coronary artery lesions (CAL) would have the T677 allele compared with patients without CAL and healthy subjects.
    Methods: Genotypes for MTHFR were determined in 75 KD patients (male : female ratio 52:23) and 238 healthy subjects (male : female ratio, 110:128) by the polymerase chain reaction and restriction fragment length polymorphism method.
    Results: The results indicated that female KD patients had a significantly higher frequency of the TT genotype compared with female control subjects. In the female population, the frequency of the TT genotype in patients with initial coronary aneurysm was significantly lower than in patients without this manifestation. Analysis of the data for the male population showed that the frequency of the TT genotype in KD patients developing coronary stenosis, occlusion or myocardial infarction was higher than that in those without these manifestations, although the difference was statistically insignificant.
    Conclusions: The TT genotype may protect female KD patients against initial aneurysm formation and predispose male KD patients to severe coronary complications. Further large-scale studies may be required to confirm the contribution of homocysteine in the coronary sequelae of KD.

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  • Systemic inflammatory response syndrome and acute renal failure associated with Hemophilus influenzae septic meningitis 査読

    M Nishimura, H Tsukahara, M Hiraoka, Y Osaka, Y Ohshima, A Tanizawa, M Mayumi

    AMERICAN JOURNAL OF NEPHROLOGY   20 ( 3 )   208 - 211   2000年5月

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    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  

    Sepsis is often associated with a downward spiral through a spectrum of systemic inflammatory response syndrome (SIRS) culminating in organ failure and death. Here we present a 3-year-old girl with Hemophilus influenzae septic meningitis who developed SIRS and acute renal failure. In the initial stage, the patient showed uremia, cytopenia, disseminated intravascular coagulation, elevation of tissue enzyme and ferritin values, hemophagocytosis and overproduction of nitric oxide. The serum cytokine profile revealed increased levels of soluble interleukin (IL)-2 receptor, IL-6, IL-10 and tumor necrosis factor alpha. The patient responded positively to early and intensive interventions including antibiotics, repeated exchange transfusions, dexamethasone and high-dose gamma-globulin. The above laboratory abnormalities almost normalized with clinical improvement. We consider that SIRS was probably responsible for the sequence of events resulting in renal failure in this case, and suggest that renal failure should be included among the serious complications of SIRS associated with Hemophilus influenzae septic meningitis. Copyright (C) 2000 S. Karger AG, Basel.

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  • インフルエンザ菌による髄膜炎に伴いsystemic inflammatory response syndrome(SIRS)及び急性腎不全をきたした1例

    塚原 宏一, 西村 光敏, 平岡 政弘, 木村 宏輝, 大嶋 勇成, 谷澤 昭彦, 木川 芳春, 眞弓 光文

    日本小児科学会雑誌   104 ( 3 )   381 - 381   2000年3月

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    記述言語:日本語   出版者・発行元:(公社)日本小児科学会  

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  • Oxidative stress in childhood meningitis: measurement of 8-hydroxy-2 '-deoxyguanosine concentration in cerebrospinal fluid 査読

    H Tsukahara, T Haruta, N Ono, R Kobata, Y Fukumoto, M Hiraoka, M Mayumi

    REDOX REPORT   5 ( 5 )   295 - 298   2000年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W S MANEY & SONS LTD  

    To examine the involvement of reactive oxygen species, we measured the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative stress, in cerebrospinal fluid samples from 63 children with and without meningitis. We observed that the mean concentration of 8-OHdG in samples obtained during the early phase of bacterial meningitis, but not aseptic meningitis, was significantly higher than that in control samples. Clinical and laboratory improvement was associated with a fall in the 8-OHdG concentration in the patients with bacterial meningitis. Our findings suggest the presence of enhanced oxidative stress in the central nervous system of children with bacterial meningitis.

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  • シンポジウム (VI)「全身性炎症性疾患の免疫・アレルギー学的側面」

    古川 漸, 眞弓 光文, 横田 俊平, 塚原 宏一, 谷内江 昭宏, 松原 知代, 篠原 真

    日本小児アレルギー学会誌   14 ( 3 )   351 - 355   2000年

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    記述言語:日本語   出版者・発行元:THE JAPANESE SOCIETY OF PEDIATRIC ALLERGY AND CLINICAL IMMUNOLOGY  

    DOI: 10.3388/jspaci.14.351

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  • Early (4-7 days of age) dexamethasone therapy for prevention of chronic lung disease in preterm infants 査読

    H Tsukahara, Y Watanabe, M Yasutomi, R Kobata, S Tamura, K Kimura, M Hiraoka, M Mayumi

    BIOLOGY OF THE NEONATE   76 ( 5 )   283 - 290   1999年11月

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    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 conducted a comparative study to evaluate whether early (4-7 days of age) tow-dose dexamethasone (DEX) therapy in preterm infa nts with surfactant-pretreated respiratory distress syndrome (RDS) would facilitate extubation and improve the clinical outcome. Twenty-six preterm infants with surfactant-pretreated RDS who were oxygen- and ventilator-dependent at 4 days of postnatal age were enrolled. Twelve infants were in the historical comparison group, and 14 infants were assigned to receive DEX 0.125 mg/kg i.v., every 12 h, for a total of 6 doses. At study entry, the two groups had a comparable clinical status. DEX therapy significantly facilitated weaning from mechanical ventilation (median interval, 6 vs. 24 days, p &lt; 0.005) and shortened duration of oxygen supplementation (9 vs. 28 days, p &lt; 0.05) as compared with the historical comparison group. At 28 days of age, the occurrence of chronic lung disease (CLD) was significantly lower (1/14 vs. 6/12, p &lt; 0.05) and there was a significant decrease in the incidence of ventilator dependence (0/14 vs. 5/12, p &lt; 0.05) in the DEX group. DEX therapy did not influence the incidence of significant complications such as infection, periventricular leukomalacia or retinopathy of prematurity. We conclude that in a selected high-risk group of preterm infants, early low-dose DEX treatment results in improvement in pulmonary outcome without significant side effects.

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  • Evaluation of a rapid reagent strip test for the diagnosis of childhood meningitis 査読

    H Tsukahara, T Haruta, C Hori, M Matsuda, N Ono, M Hiraoka, Y Shigematsu, M Mayumi

    PEDIATRICS INTERNATIONAL   41 ( 4 )   443 - 446   1999年8月

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    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 SCIENCE ASIA  

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  • Voiding function study with ultrasound in male and female neonates 査読

    M Hiraoka, C Hori, H Tsukahara, K Kasuga, F Kotsuji, M Mayumi

    KIDNEY INTERNATIONAL   55 ( 5 )   1920 - 1926   1999年5月

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    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 SCIENCE INC  

    Background The neonatal period has been characterized as a time when males have a much higher incidence of urinary infection and severe ureteral reflux than females. However, little information about the voiding function in the neonatal period is available.
    Methods. The bladder urine volumes, before and after voiding, and urinary how rates were determined with the use of noninvasive voiding-provocation maneuvers and ultrasound in the apparently normal neonates.
    Results. There was no significant difference in the prevoid bladder urine volume between the two sexes. After they were stimulated to enhance the tension of their abdominal wall musculature, 65 of 118 females (55.1%) and 64 of 115 males (55.7%) voided. The voiding was observed in 94 (81.0%) of the 116 neonates who had had a prevoid volume above 12 ml. The residual urine expressed as a percentage of the prevoid volume was significantly higher in the males (median, 12.0% in males vs. 3.0% in females, P &lt; 0.01), with the values being above 20% in 26 (41%) of the 64 males compared with 10 (15%) of the 65 females (P &lt; 0.01). Urinary flow rates, determined in 52 neonates, were significantly smaller in males than in females (mean +/- so, 2.6 +/- 0.9 g/second vs. 3.8 +/- 1.3 g/second, respectively, P &lt; 0.001).
    Conclusion. This voiding function study with ultrasound using noninvasive voiding-provocation maneuvers successfully revealed that male neonates have a larger residual urine volume and smaller urinary flow rates than female neonates. This study should be useful for the diagnosis of voiding dysfunction in children with abnormal urinary symptoms.

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  • Assessment of bone turnover in term and preterm newborns at birth: measurement of urinary collagen crosslink excretion 査読

    H Tsukahara, Y Watanabe, S Hirano, H Tsubokura, K Kimura, M Mayumi

    EARLY HUMAN DEVELOPMENT   53 ( 3 )   185 - 191   1999年1月

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    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 excretion of collagen crosslinks, pyridinoline and deoxypyridinoline, in term and preterm newborns at birth and evaluated the developmental changes in bone turnover. Collagen crosslink excretion in newborns was more than 10 times higher than reported adult values and several times higher than those of older children. The values were significantly higher in preterm newborns than in term newborns. In addition, a significant and inverse correlation was found between urinary collagen crosslinks and gestational age in preterm newborns. Excretion of crosslinks during this period did not correlate with beta,microglobulin, suggesting that the excretion was not directly influenced by renal function in newborns. We conclude that bone turnover assessed by measurement of collagen crosslink excretion is high at birth and that preterm newborns have higher bone turnover than term newborns. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

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  • Vesicoureteral reflux in male and female neonates as detected by voiding ultrasonography 査読

    Masahiro Hiraoka, Chikahide Hori, Hirokazu Tsukahara, Kenkou Kasuga, Yoshinori Ishihara, Fumikazu Kotsuji, Mitsufumi Mayumi

    Kidney International   55 ( 4 )   1486 - 1490   1999年

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    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 Inc.  

    Background. Vesicoureteral reflux (VUR) is assumed to be congenital, and its early diagnosis is desired in order to prevent acquired renal damage. However, the incidence of VUR in neonates remains to be revealed. Methods. Two thousand newborn babies (1048 boys and 952 girls) underwent voiding ultrasonography (an ultrasound examination of urinary tract during provoked voiding). Those who showed transient renal pelvic dilation during voiding, who had small kidneys, or who subsequently developed urinary infection underwent voiding cystourethrography. Results. Transient renal pelvic dilation was observed in 16 babies (0.8%), including one boy with small kidneys. Among the rest of the babies, one boy had a small kidney, and nine babies subsequently developed urinary infection. Voiding cystourethrography revealed VUR in 24 ureters of 16 children (11 boys and 5 girls). Dimercaptosuccinate renoscintigraphy confirmed small kidneys, with generally reduced tracer uptake in a total of three boys, all having VUR. Voiding ultrasonography detected transient renal pelvic dilation in 17 (71%) of the 24 kidneys with VUR and, strikingly, 16 of the 17 (94%) kidneys with high- grade VUR (grade III or more). Conclusion. This study effectively detected VUR in 0.8% of the neonates (mostly of high grades and predominantly in males) and voiding ultrasonography showed a decided usefulness for the detection of VUR. The male preponderance of VUR in neonates was considered to be due to the occurrence of congenitally small kidneys, with reflux found exclusively in males and easier ultrasound detection of VUR in male neonates because the majority of diagnoses are reported to be high grades of VUR.

    DOI: 10.1046/j.1523-1755.1999.00380.x

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  • Renal water channel expression in newborns: Measurement of urinary excretion of aquaporin-2 査読

    H Tsukahara, Hata, I, K Sekine, M Miura, F Kotsuji, M Mayumi

    METABOLISM-CLINICAL AND EXPERIMENTAL   47 ( 11 )   1344 - 1347   1998年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W B SAUNDERS CO  

    Aquaporin-2 (AQP-2) encodes the vasopressin-regulated "water channels" of the renal collecting duct and is excreted in human urine. We measured urinary excretion of AQP-2 by radioimmunoassay in 15 term and 10 preterm infants on day 1 and day 4 of life to determine the molecular basis of water balance during the newborn period. AQP-2 was detectable in the urine of term and preterm newborns, but AQP-2 excretion was severalfold less than the reported level in normal adults. Urinary excretion of AQP-2 significantly decreased postnatally, in parallel with a reduction in urine osmolality and arginine vasopressin (AVP) excretion. Urinary AQP-2 correlated positively and significantly with urine osmolality on days 1 and 4 and with AVP on day 1 in both groups. No significant differences were detected in AQP-2 levels between term and preterm newborns. Our findings suggest that vasopressin-regulated water channels are expressed in the renal collecting duct of both term and preterm newborns, although to a lesser extent as compared with adults, and these channels encoded by AQP-2 contribute to the urine concentrating power of the newborn kidney. Copyright (C) 1998 by W.B. Saunders Company.

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  • Urinary excretion of aquaporin-2 in term and preterm infants 査読

    H Tsukahara, Hata, I, K Sekine, M Miura, K Hata, Y Fujii, M Mayumi

    EARLY HUMAN DEVELOPMENT   51 ( 1 )   31 - 37   1998年4月

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    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  

    Aquaporin-2 (AQP-2) is a vasopressin-regulated water channel of the renal collecting duct and is excreted in human urine. We measured the urinary excretion of AQP-2 by radioimmunoassay in 14 term and 12 preterm infants aged 1 month. Excretion of AQP-2 was low compared with adults, and correlated significantly with urine osmolality in preterm infants. Our results demonstrate that AQP-2 water channels are expressed in the renal collecting duct of both term and preterm infants. (C) 1998 Elsevier Science Ireland Ltd.

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  • High-turnover osteopenia in preterm infants: Determination of urinary pyridinium cross-links of collagen 査読

    H Tsukahara, M Takeuchi, K Fujisawa, M Miura, K Hata, K Yamamoto, M Mayumi

    METABOLISM-CLINICAL AND EXPERIMENTAL   47 ( 3 )   333 - 335   1998年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W B SAUNDERS CO  

    Osteopenia is a frequent condition in preterm infants, but its pathogenesis is uncertain. In the present study, we measured longitudinal changes in the excretion of pyridinium cross-links of collagen (specific markers of bone resorption) and evaluated the relationship between collagen cross-links and other indexes of bone and renal function in preterm infants. In these infants, urinary collagen cross-links were markedly increased on day 7 and day 30 of life and at estimated full-term gestation. The values were several times higher than those of older children and almost comparable to those of healthy full-term infants. Cross-link excretion did not correlate with beta(2)-microglobulin (B2M) or N-acetyl-beta-D-glucosaminidase (NAG) activity (markers of renal function), indicating that cross-link excretion is not influenced directly by infantile renal function. High serum osteocalcin and low bone mineral density (BMD) in the lumbar spine were also observed at estimated full-term gestation, There was no significant correlation between collagen cross-link excretion and either serum osteocalcin or spine BMD. We conclude that a state of high bone turnover underlies the development of osteopenia in preterm infants. Copyright (C) 1998 by W.B. Saunders Company.

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  • Nitric oxide in septic and aseptic meningitis in children 査読

    H Tsukahara, T Haruta, Hata, I, M Mayumi

    SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION   58 ( 1 )   73 - 79   1998年2月

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    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 investigate the involvement of nitric oxide (NO) in childhood meningitis, we measured the concentrations of NO2- (a stable metabolite of NO) in serial samples of cerebrospinal fluid (CSF) from :II children with septic and 7 with aseptic meningitis and 26 control patients without meningitis. The mean concentration of NO2- in samples obtained during the early stages of septic meningitis, but not aseptic meningitis, was significantly higher than in control samples. Clinical and laboratory improvement following administration of antibiotics and dexamethasone was associated with a fall in CSF [NO2-] to normal levels in these patients. CSF [NO2-] remained almost consistently within the normal range in patients with aseptic meningitis. Our findings indicate that NO production is enhanced in the CSF compartment of children with septic meningitis and support the hypothesis that NO is involved in the pathophysiology of septic meningitis.

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  • Development of antigen-specific ige antibodies in atopic and non-atopic infants: Diagnostic value of low levels of ige against egg white in infants with atopic dermatitis 査読

    M. Mayumi, M. Saito, H. Tsukahara, S. Ito, K. Katamura

    Allergology International   47 ( 2 )   129 - 136   1998年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Society of Allergology  

    To analyze the development of antigen-specific IgE in infants and its clinical usefulness, the levels of IgE antibodies against egg white (f1) and cows' milk (f2) in 33 sera from cord blood, 118 sera from atopic dermatitis (AD) infants and 197 sera from non-atopic control infants were measured by using the CAP radioallergosorbent test (RAST) fluoro enzyme immunoassay (FEIA) system, which has a detection limit of 0.15 Ua/mL for fl and 0.20 Ua/mL for f2. No antigen-specific IgE was detected in cord blood, whereas in infants younger than 6 months of age, 38.5% of AD infants and 6.6% of the non-atopic controls showed IgE against f1 (≤0.70 Ua/mL) and 14.3 and 4.0%, respectively, showed low levels (0.15-0.70 Ua/mL) of the IgE. When the cut- off point for positive versus negative f1 RAST was set at 0.15 or 0.35 Ua/mL instead of 0.70 Ua/mL, the significance of the difference in f1 RAST- positive and -negative proportions between atopic and non-atopic infants did not change. Repeated examination of f1 RAST revealed later positive conversion in the majority of AD patients, with no detectable or very low levels (0.15-0.35 Ua/mL) of f1 -specific IgE. In infants at 6 months of age or older, 44.4 and 12.0% of AD patients and non-atopic controls, respectively, showed IgE against f1 (≤ 0.70 Ua/mL) and 37.1 and 22.6%, respectively, showed low levels (0.15-0.70 Ua/mL) of the IgE. These results suggest that f1 RAST at a concentration of 0.15 Ua/mL or higher has diagnostic value for egg allergy in AD infants, especially in infants younger than 6 months of age. The f1 RAST should be examined repeatedly in AD infants with low levels of IgE against f1. Similar results were obtained for f2- specific IgE, but there was a significant decrease in the specificity when the cut-off point was set at 0.20 Ua/mL.

    DOI: 10.2332/allergolint.47.129

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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

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    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

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    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

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    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

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  • 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

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    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.

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  • 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

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    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 (&lt;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.

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  • 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

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    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.

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  • 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

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    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.

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  • 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

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    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

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  • 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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/j.1442-200X.1996.tb03517.x

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  • FAVORABLE COURSE OF STEROID-RESPONSIVE NEPHROTIC CHILDREN WITH MILD INITIAL ATTACK 査読

    M HIRAOKA, N TAKEDA, H TSUKAHARA, K KIMURA, K TAKAGI, S HAYASHI, E KATO, K OHTA, M SUDO

    KIDNEY INTERNATIONAL   47 ( 5 )   1392 - 1393   1995年5月

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    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 SCIENCE PUBL INC CAMBRIDGE  

    The course and prognosis of idiopathic nephrotic syndrome has thus far not been found to be predicted from the severity of the manifestations at the onset. Among 66 steroid-responsive nephrotic children, eight were asymptomatic without edema and identified by chance proteinuria on a urinary screening program. The selectivity index for proteinuria (a clearance ratio of IgG to transferrin) was 0.10 or less in all of the five children examined. Ail of the eight children responded quickly to the prednisolone therapy. Grades of proteinuria and hypoalbuminemia were lower in the asymptomatic children than in the symptomatic children who presented with edema. Median proteinuria levels were 2.0 versus 4.2 g/day/m(2) (P &lt; 0.01), respectively, and mean serum albumin levels were 2.2 +/- 0.3 versus 1.8 +/- 0.4 g/dl (mean +/- SD; P &lt; 0.01), respectively. None of the eight asymptomatic children relapsed for at least one year after completion of the prednisolone treatment, while, in contrast, 30 of 58 symptomatic nephrotic children relapsed during the same one-year period (P &lt; 0.01). These findings suggest that, among steroid-responsive nephrotic children, those with mild manifestations without edema may have a milder disease and show an extremely favorable clinical course.

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  • 小児における部位別骨塩定量:DEXAを用いて 査読

    塚原宏一, 高野智子, 中井昭夫, 平岡政弘, 須藤正克, 梅崎実, 中島鉄夫, 山本和高, 石井 靖, 春木伸一

    日本小児放射線学会雑誌   8   216 - 219   1992年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Dual-Energy X-ray Absorptiometry(DEXA)の小児への応用 査読

    塚原宏一, 藤井靖史, 栗山政憲, 平岡政弘, 中井昭夫, 須藤正克, 中島鉄夫, 梅崎実, 山本和高, 石井靖, 森河浄, 林修平, 春木伸一

    日本小児放射線学会雑誌   8   70 - 71   1992年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Urinary Growth Hormone during Early Infancy: Another Index of Proximal Tubular Function 査読

    Hirokazu Tsukahara, Kiyoshi Kikuchi, Katsuji Nakamura, Masahiro Yoshimoto, Masakazu Saito, Masakatsu Sudo

    Pediatrics International   32 ( 5 )   575 - 578   1990年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/j.1442-200X.1990.tb00885.x

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  • Juvenile Nephronophthisis Diagnosed from Glucosuria Detected by Urine Screening at School 査読

    Hirokazu Tsukahara, Kiyoshi Kikuchi, Haruki Mikawa, Shinichi Fujisawa, Masahiro Yoshimoto, Masakatsu Sudo

    Pediatrics International   32 ( 5 )   548 - 551   1990年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We describe the case of an 11‐year‐old girl in whom glucosuria detected by urine screening at school was the first clue to the diagnosis of juvenile nephronophthisis (JN). On admission, she showed renal failure with combined proximal and distal tubular defects and progressive deterioration of renal function. JN should be considered in children with glucosuria. Copyright © 1990, Wiley Blackwell. All rights reserved

    DOI: 10.1111/j.1442-200X.1990.tb00878.x

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  • Improved Bone Mineral Status in Very Low Birthweight Infants Fed Human Milk Mixed with Preterm Formula 査読

    Hirokazu Tsukahara, Izuru Mitsuyoshi, Tadahiko Sakaguchi, Hitoo Fukuhara, Shuhei Hayashi, Katsuji Nakamura

    Pediatrics International   31 ( 1 )   58 - 64   1989年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The bone mineral status of very low birthweight (VLBW) infants fed exclusively their own mother's milk (group I) was compared with that of VLBW infants fed mother's milk in the initial 4 weeks followed by a 1:1 mixture of mother's milk and preterm formula containing high phosphorus (P) and calcium (Ca) (group II). In both groups, most infants showed a biochemical picture characteristic of phosphorus deficiency syndrome by the fourth week. Thereafter, serum alkaline phosphatase activity (ALP) decreased and serum P increased in all group II infants. Conversely, serum ALP rose and hypophosphatemia persisted in most group I infants. Group II had a significantly higher serum P at weeks 8 and 12 and a significantly lower ALP at week 12 than group I. Furthermore, group II had a lower incidence of severe radiographic abnormalities than group I at week 12. We confumed previous observations that VLBW infants fed exclusively human milk require P and Ca supplementation to prevent metabolic bone disease of prematurity. Copyright © 1989, Wiley Blackwell. All rights reserved

    DOI: 10.1111/j.1442-200X.1989.tb01270.x

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  • Mean Cellular Volume of Urinanry Red Blood Cells in Investigation of Hematuria 査読

    Hirokazu Tsukahara, Masahiro Yoshimoto, Kiyoshi Morikawa, Toshiharu Okada, Mitsuhiko Kuroda, Masakatsu Sudo

    Pediatrics International   31 ( 4 )   476 - 479   1989年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The mean cellular volume (MCV) of urinary red blood cells (RBCs) of pediatric patients with glomerular (group I
    n = 52) and nonglomerular (group II
    n = 21) hematuria was determined using an automated bloodell analyzer. Group I patients had a significantly lower MCV than group II (61 ± 8 w. 88 ± 15 μm3, mean ± SD
    p&lt
    0.001). With a MCV of 75 μm3 taken as the dividmg line between glomerular and nonglomerular hematuria, correct assessment of the site of bleeding was made in 67 of the 73 (92%) patients studied. Determination of the MCV of urinary RBCs is a simple noninvasive test for localizing the site of hemaw in pediatric patients. Copyright © 1989, Wiley Blackwell. All rights reserved

    DOI: 10.1111/j.1442-200X.1989.tb01335.x

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  • Phosphorus Deficiency Syndrome in Two Very Low Birthweight Infants 査読

    Hirokazu Tsukahara, Tadahiko Sakaguchi, Izuru Mitsuyoshi, Hitoo Fukuhara, Shuhei Hayashi, Katsuji Nakamura

    Pediatrics International   30 ( 4 )   520 - 525   1988年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Biochemical and radiographic abnormalities linked with phosphorus deficiency syndrome (PDS) developed in two very low birthweight (VLBW) infants fed exclusively with human milk. By increasing phosphorus (P) and calcium (Ca) intakes with the introduction of a specialized premature formula, osteopenia or rickets, as well as hypophosphatemia, hypo‐phosphaturia and increased serum alkaline phosphatase levels improved in both patients. We speculated that all VLBW infants who are being fed exclusively with human milk should be monitored for PDS and that if PDS develops, supplementation of human milk with both P and Ca appears to be necessary for its treatment. Copyright © 1988, Wiley Blackwell. All rights reserved

    DOI: 10.1111/j.1442-200X.1988.tb02546.x

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書籍等出版物

  • VURに対する抗生剤予防内服: pros and cons - 小児腎臓病専門医の立場から, 第17回日本逆流性腎症フォーラム記録集

    日本逆流性腎症フォーラム  2009年 

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  • 新生児の低血糖, 今日の治療指針 2010年版 - 私はこう治療している

    医学書院  2009年 

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  • 小児における二重エネルギーX線吸収測定法(DXA)を用いた腰椎骨塩定量のこれまでの英文論文報告の総括, 第26回小児代謝性骨疾患研究会発表論文集

    小児代謝性骨疾患研究会  2009年 

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  • VURに対する抗生剤予防内服: pros and cons - 小児腎臓病専門医の立場から, 第17回日本逆流性腎症フォーラム記録集

    日本逆流性腎症フォーラム  2009年 

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  • 新生児の低血糖, 今日の治療指針 2010年版 - 私はこう治療している

    医学書院  2009年 

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  • 小児における二重エネルギーX線吸収測定法(DXA)を用いた腰椎骨塩定量のこれまでの英文論文報告の総括, 第26回小児代謝性骨疾患研究会発表論文集

    小児代謝性骨疾患研究会  2009年 

     詳細を見る

  • 電解質管理, 新生児内分泌ハンドブック

    メデイカ出版  2008年 

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  • 超低出生体重児の消化管成熟に向けた治療戦略: 肺サーファクタントを用いた動物実験, 福井大学重点研究成果集

    福井大学  2008年 

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  • 小児科領域における酸化ストレスとレドックス制御の病態学的意義, 第8回小児医学川野賞受賞講演抄録集

    川野小児医学奨学財団  2008年 

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  • カルシウム代謝・骨代謝, 新生児内分泌ハンドブック

    メデイカ出版  2008年 

     詳細を見る

  • 電解質管理, 新生児内分泌ハンドブック

    メデイカ出版  2008年 

     詳細を見る

  • 小児科領域における酸化ストレスとレドックス制御の病態学的意義, 第8回小児医学川野賞受賞講演抄録集

    川野小児医学奨学財団  2008年 

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  • カルシウム代謝・骨代謝, 新生児内分泌ハンドブック

    メデイカ出版  2008年 

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  • 胎児期・乳幼児期・学童期・思春期においてアルギニン代謝が循環制御に果たす役割についての分子医学的研究, 福井大学重点研究成果報告書

    2007年 

     詳細を見る

  • 低カルシウム血症, NICUマニュアル

    金原出版  2007年 

     詳細を見る

  • 未熟児くる病, NICUマニュアル

    金原出版  2007年 

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  • 尿検査: 尿中細菌, 小児臨床検査ガイド

    文光堂  2006年 

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  • ショック, 鑑別診断の手引き: 『小児救急の手引き』フローチャートより

    臨床医薬研究協会  2006年 

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  • ショック, 小児救急の手引き 下巻

    臨床医薬研究協会  2005年 

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  • Postnatal corticosteroid therapy for bronchopulmonary dysplasia in preterm infants: A neonatal clinical dilemma that demands a quick answer, Recent Research Developments in Respiratory & Critical Care Medicine

    Research Signpost  2005年 

     詳細を見る

  • ネルソン小児科学

    エルゼビア・ジャパン  2005年 

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  • ELISA解析と糖尿病, 酸化ストレスマーカー

    学会出版センター  2005年 

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  • 輸液の基本, 166-169, コア・ローテイション小児科

    金芳堂  2003年 

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  • 低出生体重児と消化管アレルギー : ミルクアレルギーと壊死性腸炎, 第3回新生児栄養フォーラム論文集

    2003年 

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  • 輸液療法の基礎:新生児の輸液の特殊性を知る, Neonatal Care 2003年春季増刊号 (新生児輸液マニュアル)

    2003年 

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  • Tsukahara H, Ishida T, Mayumi M. Gas-phase oxidation and desproportionation of nitricoxide.

    Methods Enzymol Academic Press  2002年 

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  • Tsukahara H, Ishida T, Mayumi M. Gas-phase oxidation and desproportionation of nitricoxide.

    Methods Enzymol Academic Press  2002年 

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▼全件表示

MISC

  • コロナ禍における鼻腔検体採取方法に関する検討

    八代 将登, 茂原 研司, 宇田 和宏, 斎藤 有希惠, 津下 充, 塚原 宏一

    日本小児感染症学会総会・学術集会プログラム・抄録集   53回   166 - 166   2021年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児感染症学会  

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  • 医学部学生に対する予防接種記録判定方法の現状と問題点

    茂原 研司, 八代 将登, 宇田 和宏, 塚原 宏一

    日本環境感染学会総会プログラム・抄録集   36回   253 - 253   2021年9月

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    記述言語:日本語   出版者・発行元:(一社)日本環境感染学会  

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  • 新型コロナウイルス感染症(COVID-19)流行の現況と展望

    塚原 宏一

    現代産婦人科   69 ( Suppl. )   S35 - S35   2021年9月

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    記述言語:日本語   出版者・発行元:中国四国産科婦人科学会  

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  • 経口負荷経験で診断に至った食用クラゲアレルギーの1小児例

    津下 充, 茂原 研司, 宇田 和宏, 斎藤 有希惠, 八代 将登, 池田 政憲, 塚原 宏一

    日本小児アレルギー学会誌   35 ( 4 )   385 - 385   2021年9月

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    記述言語:日本語   出版者・発行元:(一社)日本小児アレルギー学会  

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  • 医学部学生に対する予防接種記録の判定方法に関する検討

    八代 将登, 茂原 研司, 宇田 和宏, 塚原 宏一

    日本環境感染学会総会プログラム・抄録集   36回   253 - 253   2021年9月

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    記述言語:日本語   出版者・発行元:(一社)日本環境感染学会  

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  • 岡山大学病院での急性単純性膀胱炎に対する尿検査実施状況および経口抗菌薬の処方動向に関する実態調査

    森下 陽介, 東恩納 司, 稲葉 裕明, 草野 展周, 塚原 宏一

    日本環境感染学会総会プログラム・抄録集   36回   298 - 298   2021年9月

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    記述言語:日本語   出版者・発行元:(一社)日本環境感染学会  

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  • 岡山大学病院における抗菌薬適正使用支援チーム(AST)の取り組みと評価

    東恩納 司, 森下 陽介, 稲葉 裕明, 草野 展周, 塚原 宏一

    日本環境感染学会総会プログラム・抄録集   36回   245 - 245   2021年9月

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    記述言語:日本語   出版者・発行元:(一社)日本環境感染学会  

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  • 起立性調節障害患者のQOLについての検討(第3報) 治療後の変化

    重安 良恵, 岡田 あゆみ, 藤井 智香子, 田中 知絵, 赤木 朋子, 椙原 彰子, 堀内 真希子, 塚原 宏一

    子どもの心とからだ   30 ( 2 )   247 - 247   2021年8月

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    記述言語:日本語   出版者・発行元:(一社)日本小児心身医学会  

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  • 起立性調節障害患者の下肢血行動態についての検討

    藤井 智香子, 岡田 あゆみ, 重安 良恵, 赤木 朋子, 田中 知絵, 椙原 彰子, 堀内 真希子, 塚原 宏一

    子どもの心とからだ   30 ( 2 )   229 - 229   2021年8月

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    記述言語:日本語   出版者・発行元:(一社)日本小児心身医学会  

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  • 心身症の子どものP-Fスタディ(Picture Frustration Study)の特徴

    椙原 彰子, 岡田 あゆみ, 藤井 智香子, 重安 良恵, 田中 知絵, 赤木 朋子, 堀内 真希子, 塚原 宏一

    子どもの心とからだ   30 ( 2 )   228 - 228   2021年8月

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    記述言語:日本語   出版者・発行元:(一社)日本小児心身医学会  

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  • 食物アレルゲン 経口負荷試験で診断に至った食用クラゲアレルギーの1小児例

    津下 充, 茂原 研司, 斎藤 有希恵, 八代 将登, 池田 政憲, 塚原 宏一

    アレルギー   70 ( 6-7 )   788 - 788   2021年8月

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    記述言語:日本語   出版者・発行元:(一社)日本アレルギー学会  

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  • チームアプローチによって疼痛が改善した消化管GVHDの1例

    藤本 耕慈, 藤井 智香子, 岡田 あゆみ, 重安 良恵, 椙原 彰子, 堀内 真希子, 塚原 宏一

    子どもの心とからだ   30 ( 2 )   236 - 236   2021年8月

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    記述言語:日本語   出版者・発行元:(一社)日本小児心身医学会  

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  • 妊娠高血圧症の母親から生まれた児における3歳の肥満有病率および関連リスク因子

    光井 崇, 谷 和祐, 三島 桜子, 鷲尾 洋介, 吉本 順子, 塚原 宏一, 増山 寿

    日本周産期・新生児医学会雑誌   57 ( Suppl. )   P158 - P158   2021年6月

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    記述言語:日本語   出版者・発行元:(一社)日本周産期・新生児医学会  

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  • 妊娠高血圧症候群の母体より出生したSGA児のcatch-upに影響する因子

    三島 桜子, 光井 崇, 三苫 智裕, 横畑 理美, 大平 安希子, 谷 和祐, 牧 尉太, 衛藤 英理子, 早田 桂, 鷲尾 洋介, 吉本 順子, 塚原 宏一, 増山 寿

    日本周産期・新生児医学会雑誌   57 ( Suppl. )   P218 - P218   2021年6月

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    記述言語:日本語   出版者・発行元:(一社)日本周産期・新生児医学会  

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  • ステロイド使用中のネフローゼ症候群における骨微細構造の検討

    宮原 宏幸, 宮井 貴之, 二川 奈都子, 宮原 大輔, 長谷川 高誠, 塚原 宏一

    日本腎臓学会誌   63 ( 4 )   500 - 500   2021年6月

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    記述言語:日本語   出版者・発行元:(一社)日本腎臓学会  

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  • 日本小児腎臓病学会のBCP(事業継続計画) 日本小児腎臓病学会のBCP 医療安全・倫理・災害対応・COI委員会から

    塚原 宏一

    日本小児腎臓病学会雑誌   34 ( 1Suppl. )   52 - 52   2021年5月

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    記述言語:日本語   出版者・発行元:(一社)日本小児腎臓病学会  

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  • ステロイド使用中のネフローゼ症候群における骨微細構造の評価

    宮原 宏幸, 宮井 貴之, 二川 奈都子, 長谷川 高誠, 宮原 大輔, 塚原 宏一

    日本小児腎臓病学会雑誌   34 ( 1Suppl. )   137 - 137   2021年5月

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    記述言語:日本語   出版者・発行元:(一社)日本小児腎臓病学会  

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  • 大学病院における医療安全管理

    塚原 宏一

    日本小児腎臓病学会雑誌   34 ( 1Suppl. )   48 - 48   2021年5月

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    記述言語:日本語   出版者・発行元:(一社)日本小児腎臓病学会  

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  • 岡山県における新型コロナウイルス感染症流行の疫学的特徴

    東恩納 司, 千堂 年昭, 草野 展周, 塚原 宏一

    岡山医学会雑誌   133 ( 1 )   43 - 48   2021年4月

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    記述言語:日本語   出版者・発行元:岡山医学会  

    岡山県の新型コロナウイルス(SARS-CoV-2)感染者の発生状況を詳細に調査した。調査対象者は、岡山県において2020年3月22日から8月24日までの間にPCR法またはLAMP法にてSARS-CoV-2感染者と公表された患者で、第1波で25人、第2波で116人の合計141人であった。第1波では50代の感染者が29%で最も多く、50代以降で全体の54%を占めていた。第2波では20代の感染者が40%で最も多く、30代が14%、40代が17%であり、20代から40代が全体の71%を占めていた。居住地は、第1波、第2波ともに岡山市に居住する感染者が最も多く、それぞれ、全体の65%、73%を占めていた。第2波では、第1波と比較して非同居間での感染割合が高かった。疫学リンク不明例を除いた検討(第1波6人、第2波62人)では、20歳未満より20歳以上への感染、20歳未満同士の感染の事例はなかった。第1波ではクラスターはなかったが、第2波では三つのクラスターが認められた。クラスターはすべて岡山市で発生しており、各クラスターにおける感染者数は5人、8人、6人で、総計19人であった。疫学リンク不明例を除いた検討であるが、第1波(総計6人)、第2波(総計62人)におけるPCR陽性確認間隔について、それぞれの平均±標準偏差/中央値(最小値-最大値)は、第1波で0.8±0.8日/1(0〜2)日、第2波で2.0±1.4日/2(0〜9)であった。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00175&link_issn=&doc_id=20210419150005&doc_link_id=10.4044%2Fjoma.133.43&url=https%3A%2F%2Fdoi.org%2F10.4044%2Fjoma.133.43&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  • 重症神経疾患の病原体同定のための検体採取の実態解明

    八代 将登, 多屋 馨子, 茂原 研司, 津下 充, 塚原 宏一

    感染症学雑誌   95 ( 臨増 )   275 - 275   2021年4月

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    記述言語:日本語   出版者・発行元:(一社)日本感染症学会  

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  • 新生児医療における酸化ストレス制御の意義

    塚原 宏一

    日本産科婦人科学会雑誌   73 ( 臨増 )   S - 43   2021年3月

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    記述言語:日本語   出版者・発行元:(公社)日本産科婦人科学会  

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  • 急性散在性脳脊髄炎との鑑別に苦慮した中枢神経原発悪性リンパ腫の1例

    宮原 大輔, 嶋田 明, 道上 理絵, 兵頭 勇紀, 花岡 義行, 秋山 倫之, 塚原 宏一, 小林 勝弘

    日本小児科学会雑誌   125 ( 2 )   271 - 271   2021年2月

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    記述言語:日本語   出版者・発行元:(公社)日本小児科学会  

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  • 小児科で経験する過敏性腸症候群の特徴

    藤井 智香子, 岡田 あゆみ, 重安 良恵, 塚原 宏一

    心身医学   61 ( 1 )   57 - 63   2021年1月

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    記述言語:日本語   出版者・発行元:(一社)日本心身医学会  

    過敏性腸症候群(irritable bowel syndrome:IBS)は児童・思春期の代表的な機能性消化管疾患であるが、その実態については不明な点も多い。IBSは心理的ストレスの影響を受けやすく、患者の心理社会的背景を理解することは適切な治療介入につながると考えられる。児童・思春期のIBS患者の特徴を明らかにすることを目的に、岡山大学病院小児科を受診したIBS患者のうち発症が18歳以下であった69例の性別や併存疾患などの特徴について検討を行った。男性35例、女性34例で、59例は不登校状態にあり、外出困難をきたしている症例もあった。併存疾患として起立性調節障害やアレルギー性疾患を有する症例が多く、24例が自閉スペクトラム症(autism spectrum disorder:ASD)の診断を受けていた。ASDの感覚過敏やこだわりが強いという特性が、症状の遷延や訴えの増加につながる可能性があり、発達特性に留意して診療を行うことが必要であると考えられた。また男性に外出困難を伴う症例を多く認め、このような症例では特に、環境調整や心理療法を含めた対応が有効だった。(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00677&link_issn=&doc_id=20210112140008&doc_link_id=%2Fcv6jpsym%2F2021%2F006101%2F010%2F0057-0063%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcv6jpsym%2F2021%2F006101%2F010%2F0057-0063%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 【新型コロナウイルス感染症】総論および岡山大学病院における新型コロナウイルス感染症への対応

    塚原 宏一

    岡山医学会雑誌   132 ( 3 )   152 - 162   2020年12月

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    記述言語:日本語   出版者・発行元:岡山医学会  

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  • 心因性腹痛が疑われた小児好酸球性消化管疾患の1例

    國近 公介, 吉川 知伸, 宮原 大輔, 藤井 洋輔, 藤井 智香子, 八代 将登, 岡田 あゆみ, 塚原 宏一

    子どもの心とからだ   29 ( 3 )   281 - 285   2020年11月

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    記述言語:日本語   出版者・発行元:(一社)日本小児心身医学会  

    好酸球性消化管疾患は慢性の嘔吐や腹痛の原因となり、内視鏡検査所見で非特異的な所見を呈する症例や肉眼的な異常を呈さない症例では診断が難しい場合がある。今回、慢性の嘔吐・腹痛があり、心因性の腹痛と考えられていたが、アレルギー素因があることから好酸球性消化管疾患が疑われ、上部消化管内視鏡検査で粘膜生検をすることで、好酸球性消化管疾患と診断することができた症例を経験した。プロトンポンプ阻害薬およびロイコトリエン受容体拮抗薬による治療を開始し、症状の改善を認めた。慢性の消化器症状を有する患者でアレルギー素因がある場合には、好酸球性消化管疾患を鑑別に加える必要があると考えられた。(著者抄録)

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  • 嘔吐恐怖症に認知行動療法(Cognitive behavioral therapy:CBT)を施行した14歳女子例

    住友 裕美, 藤井 智香子, 岡田 あゆみ, 重安 良恵, 椙原 彰子, 堀内 真希子, 塚原 宏一

    子どもの心とからだ   29 ( 3 )   298 - 304   2020年11月

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    記述言語:日本語   出版者・発行元:(一社)日本小児心身医学会  

    認知行動療法(Cognitive behavioral therapy:CBT)は、不安や恐怖に対する有効性が実証されており、近年小児領域でも実施が増えている。しかし、小児の場合は言語理解や認知能力が発達途上のため、適応には配慮が必要である。嘔吐恐怖症(phagophobia)は、「嘔吐」に対する単一の恐怖症である。従来、成人の嘔吐恐怖症に対する治療法としてCBTが有効であるという報告は多かったが、小児での報告は少ない。今回、嘔吐恐怖症に対しCBTを施行した症例について、その有効性を含めて検討し報告した。症例は14歳女子、受診の1年前から嘔気や呼吸苦を自覚し、以降外出が困難となっていた。認知再構成法などのCBTを実施し、約1年後に外出や外食が可能となった。患児に治療意欲があり、CBTモデルに沿って振り返る力があったことから、早期の改善を得た。本症の小児例においてもCBTは有効と考えた。(著者抄録)

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  • インフルエンザA(H1N1)pdm09による急性呼吸窮迫症候群に対して体外式膜型人工肺とペラミビル・バロキサビルマルボキシル併用療法で改善した一例

    津下 充, 茂原 研司, 斎藤 有希惠, 八代 将登, 塚原 宏一

    日本小児感染症学会総会・学術集会プログラム・抄録集   52回   206 - 206   2020年11月

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    記述言語:日本語   出版者・発行元:(一社)日本小児感染症学会  

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  • 重症食物アレルギーにおける腸管上皮バリアに関連した血清バイオマーカーの検討

    津下 充, 茂原 研司, 斎藤 有希惠, 八代 将登, 池田 政憲, 塚原 宏一

    アレルギー   69 ( 臨時増刊号 )   290 - 290   2020年10月

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    記述言語:日本語   出版者・発行元:(一社)日本アレルギー学会  

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  • 小児造血幹細胞移植患者において、タクロリムス経口製剤の生体利用率に影響を及ぼす因子に関する検討

    金光 喜一郎, 頼藤 貴志, 石田 悠志, 藤原 かおり, 鷲尾 佳奈, 嶋田 明, 塚原 宏一

    日本小児血液・がん学会雑誌   57 ( 4 )   327 - 327   2020年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • 【抗菌薬の「なぜ?」に答える】造血幹細胞移植時の予防抗微生物薬の選択

    津下 充, 塚原 宏一

    小児内科   52 ( 10 )   1494 - 1498   2020年10月

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    記述言語:日本語   出版者・発行元:(株)東京医学社  

    <Key Points>(1)造血幹細胞移植では移植後の遷延する免疫不全によって感染症のリスクが増加するため、リスクに応じた抗微生物薬の予防投薬が必要である。(2)抗菌薬の予防投与の有用性は確立しておらず、耐性菌増加も懸念されており、患者の背景因子を考慮した予防投与が推奨される。(3)抗真菌薬の予防投与の第一選択薬はフルコナゾールであるがアスペルギルス症に無効であり、ミカファンギンやポリコナゾールの有用性が報告される。(4)単純ヘルペスウイルス・水痘帯状疱疹ウイルスの発症予防にアシクロビルが有効である。(著者抄録)

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  • 重症食物アレルギーにおける腸管上皮バリアに関連した血清バイオマーカーの検討

    津下 充, 茂原 研司, 斎藤 有希惠, 八代 将登, 池田 政憲, 塚原 宏一

    日本小児アレルギー学会誌   34 ( 4 )   484 - 484   2020年9月

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    記述言語:日本語   出版者・発行元:(一社)日本小児アレルギー学会  

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  • 岡山大学病院Family support teamの発足とその活動報告

    塚原 紘平, 塚原 宏一, 中尾 篤典, 虐待連絡委員会,Family support team

    日本小児科学会雑誌   124 ( 8 )   1300 - 1300   2020年8月

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    記述言語:日本語   出版者・発行元:(公社)日本小児科学会  

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  • 起立性調節障害患者のP-Fスタディに関する研究

    椙原 彰子, 岡田 あゆみ, 田中 知絵, 赤木 朋子, 藤井 智香子, 重安 良恵, 堀内 真希子, 塚原 宏一

    子どもの心とからだ   29 ( 2 )   225 - 225   2020年8月

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    記述言語:日本語   出版者・発行元:(一社)日本小児心身医学会  

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  • 回避・制限性食物摂取症(制限摂食)の男児例

    藤井 智香子, 岡田 あゆみ, 重安 良恵, 椙原 彰子, 堀内 真希子, 田中 知絵, 赤木 朋子, 塚原 宏一

    日本小児科学会雑誌   124 ( 8 )   1301 - 1301   2020年8月

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    記述言語:日本語   出版者・発行元:(公社)日本小児科学会  

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  • 起立性調節障害患者のQOLについての検討(第2報)

    重安 良恵, 岡田 あゆみ, 田中 知絵, 赤木 朋子, 藤井 智香子, 椙原 彰子, 堀内 真希子, 塚原 宏一

    子どもの心とからだ   29 ( 2 )   217 - 217   2020年8月

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    記述言語:日本語   出版者・発行元:(一社)日本小児心身医学会  

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  • 視神経低形成に下垂体低形成を合併した3例

    二川 奈都子, 長谷川 高誠, 塚原 宏一

    日本内分泌学会雑誌   96 ( 1 )   286 - 286   2020年8月

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    記述言語:日本語   出版者・発行元:(一社)日本内分泌学会  

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  • MT Seminar 酸化ストレスと酸化ストレスマーカーの知識

    塚原 宏一, 馬場 健児, 鷲尾 洋介, 大野 直幹

    Medical Technology   48 ( 7 )   786 - 796   2020年7月

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    記述言語:日本語   出版者・発行元:医歯薬出版(株)  

    <要点>・酸化ストレスは、内部・外部刺激により生体内で活性酸素群(活性窒素も含む)が抗酸化システムで捕捉しきれないほど過剰に生じる状況である。・酸化ストレス亢進は血管内皮障害と深く関連する。とりわけ、血管内皮での一酸化窒素(nitric oxide;NO)生成は生体のレドックス環境を保持するうえで必須である。酸化ストレス亢進はarginineを基質とするNO合成を抑制し、内因性NO合成酵素阻害因子であるasymmetric dimethylarginineの生成を刺激する。・小児の急速進行性疾患、慢性遷延性疾患ではしばしば酸化ストレスが増幅され、生体の構造や機能が酸化劣化を受けて、組織障害が不可逆的に進展する。これらの疾患の治療、管理において酸化ストレスを制御することが重要である。そのためには酸化ストレスの病態生理、それへの防御機制を把握し、特異的マーカーを用いて患者の酸化ストレス環境を非〜低侵襲的に評価することが必要である。・小児医療の現場で実施される種々の治療は酸化ストレス制御を目指すものでもあるが、今後は"レドックス"に関連してより特異性の高い細胞機能修飾薬が開発され、それらが重症疾患への集学治療のなかに組み込まれていくことが期待される。(著者抄録)

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  • 身体症状を窓口としてつながった思春期女子の1例

    椙原 彰子, 藤井 智香子, 堀内 真希子, 田中 知絵, 赤木 朋子, 重安 良恵, 岡田 あゆみ, 塚原 宏一

    小児心身症研究   ( 27 )   14 - 21   2020年6月

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    記述言語:日本語   出版者・発行元:日本小児心身医学会-中国四国地方会  

    行動化のある思春期女子に小児科医、臨床心理士で行った母子並行面接の過程を報告する。症例は、朝起きられず登校しないことを母が心配して、中学3年時に来院した。初期は体調改善を目標に小児科医単独で治療を行った。高校入学後より気分の変動が激しくなり、医師より、薬物療法、臨床心理士による支持的カウンセリング、認知行動療法が提案された。試みに臨床心理士との面接を数回実施し、本人は支持的カウンセリングを選択したが、本人の特徴を考慮して認知行動療法を取り入れた統合的カウンセリングを行った。徐々に現実的な行動や相談が出来るようになり、自己理解が深まって通学を維持できた。初期に治療者と共有しやすく心理的負担が少ない身体症状を介した診療によって治療継続できたことが有効であった。また、行動化に限界設定を行い、認知行動療法を取り入れた治療が有効であった。(著者抄録)

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  • 起立性調節障害治療における学校連携に関するアンケート調査

    田中 知絵, 岡田 あゆみ, 赤木 朋子, 藤井 智香子, 重安 良恵, 椙原 彰子, 堀内 真希子, 塚原 宏一

    小児心身症研究   ( 27 )   30 - 30   2020年6月

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    記述言語:日本語   出版者・発行元:日本小児心身医学会-中国四国地方会  

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  • リストカット、大量服薬を認めた思春期女子の1例

    椙原 彰子, 藤井 智香子, 堀内 真希子, 田中 知絵, 赤木 朋子, 重安 良恵, 岡田 あゆみ, 塚原 宏一

    小児心身症研究   ( 27 )   33 - 33   2020年6月

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    記述言語:日本語   出版者・発行元:日本小児心身医学会-中国四国地方会  

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  • 起立性調節障害診療における学校連携に関するアンケート調査

    田中 知絵, 岡田 あゆみ, 赤木 朋子, 藤井 智香子, 重安 良恵, 椙原 彰子, 堀内 真希子, 塚原 宏一

    小児心身症研究   ( 27 )   2 - 7   2020年6月

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    記述言語:日本語   出版者・発行元:日本小児心身医学会-中国四国地方会  

    起立性調節障害(Orthostatic Dysregulation:OD)は不登校を伴いやすく、その診療に際しては学校との疾病理解の共有と連携が必要である。今回我々は、学校連携において問題となりやすい連絡方法と周囲への説明に注目して調査を行った。対象:2018年8月1日〜2019年3月31日に当院子どものこころ診療部(現・小児心身医療科)を受診しODと診断され、初診時に年間90日以上の長期不登校状態であった患者とその保護者で、各15例から回答を得た。方法:無記名式アンケート調査で、選択式の設問と自由記述を行った。結果:欠席時に学校からの連絡を希望したのは、患者8人(53%)、保護者13人(87%)だった。連絡頻度は患者は様々だったが、保護者は週1回の希望が最も多かった。先生から友達への病気の説明を希望した患者は5人(33%)だった。考察:学校-家庭間の連絡は、事前に方法や頻度などを相談しておくことが必要となる。また友達への病気の説明は、患者に内容を確認し希望する場合にのみ行うことが望ましいと考えた。(著者抄録)

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  • 入院中の子どもの心理・発達支援に関する研究

    椙原 彰子, 岡田 あゆみ, 堀内 真希子, 赤木 朋子, 藤井 智香子, 重安 良恵, 塚原 宏一

    子どもの心とからだ   29 ( 1 )   27 - 32   2020年5月

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    記述言語:日本語   出版者・発行元:(一社)日本小児心身医学会  

    慢性疾患のために長期入院している子どもに、心理社会的発達を支援することは、いうまでもなく重要である。現在、医師のみならずさまざまな職種が連携して子どもや保護者に心理社会的発達支援を行っており、そのニーズは高まっている。しかし、日本の小児医療においては専門職の配置も少なく、支援体制づくりの遅れが指摘されている。今回、岡山県内の小児入院病床を有する施設を対象に、入院中の子どもの心理社会的発達支援の実態調査を行い、課題と方策を検討した。その結果、看護師、臨床心理士、病棟保育士などの多職種が個別的また日常生活の中で子どもの心理社会的発達支援を行っていることが分かった。課題として、共通認識をもちにくい、専門知識の不足が指摘され、なかでも「病児を抱えた家族の心理」が得たい知識として挙げられた。今後、カンファレンスや家族支援ツールによる情報共有、講習会の開催による知識の向上などを図ることが必要と考えられた。(著者抄録)

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  • 【[必携]専攻医と指導医のための新生児診療到達目標】疾患別到達目標 代謝内分泌疾患 未熟児骨減少症

    塚原 宏一, 岡村 朋香, 大野 直幹

    周産期医学   50 ( 4 )   676 - 680   2020年4月

  • 入院前の肝炎ウイルス検査結果について陰性者も含め説明する体制構築

    難波 志穂子, 宮村 純子, 足立 史帆, 山科 由美子, 石田 絵里, 畑中 信子, 岩崎 哲也, 塚原 宏一, 草野 展周, 安中 哲也, 池田 房雄, 高木 章乃夫, 岡田 裕之

    肝臓   61 ( Suppl.1 )   A243 - A243   2020年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • X染色体性の遺伝形式が示唆されるが原因遺伝子が不明なDent病の兄弟例

    宮井 貴之, 宮原 宏幸, 片山 寿夫, 高岩 正典, 田中 弘之, 塚原 宏一

    日本小児腎臓病学会雑誌   33 ( 1 )   95 - 95   2020年4月

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    記述言語:日本語   出版者・発行元:(一社)日本小児腎臓病学会  

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  • 酸化ストレス制御と小児疾患治療

    塚原 宏一

    日本小児腎臓病学会雑誌   33 ( 1 )   85 - 85   2020年4月

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    記述言語:日本語   出版者・発行元:(一社)日本小児腎臓病学会  

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  • 比較的早期から経過観察できた若年性ネフロン癆の1例

    宮井 貴之, 宮原 宏幸, 森貞 直哉, 飯島 一誠, 塚原 宏一

    日本小児腎臓病学会雑誌   33 ( 1 )   85 - 86   2020年4月

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    記述言語:日本語   出版者・発行元:(一社)日本小児腎臓病学会  

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  • 当科で尿中L-FABPを測定した症例の後方視的検討

    宮井 貴之, 吉川 知伸, 塚原 宏一

    日本小児腎臓病学会雑誌   33 ( 1 )   69 - 69   2020年4月

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    記述言語:日本語   出版者・発行元:(一社)日本小児腎臓病学会  

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  • 経過観察中に尿蛋白が大きく増減した4歳女児の一例

    宮井 貴之, 清水 順也, 神農 陽子, 岡田 あゆみ, 塚原 宏一

    日本小児腎臓病学会雑誌   33 ( 1 )   76 - 76   2020年4月

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    記述言語:日本語   出版者・発行元:(一社)日本小児腎臓病学会  

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  • 小児リウマチ性疾患における酸化ストレスマーカーの有用性について

    八代 将登, 茂原 研司, 斎藤 有希惠, 藤井 洋輔, 津下 充, 池田 政憲, 塚原 宏一

    岡山医学会雑誌   132 ( 1 )   47 - 47   2020年4月

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    記述言語:日本語   出版者・発行元:岡山医学会  

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  • 小児がん患者に対する歯科介入の効果について

    吉田 衣里, 森川 優子, 平野 慶子, 松三 友紀, 仲野 道代, 嶋田 明, 塚原 宏一

    小児歯科学雑誌   58 ( 地方会抄録号 )   67 - 67   2020年2月

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    記述言語:日本語   出版者・発行元:(公社)日本小児歯科学会  

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  • 岡山大学病院外来歯科領域における経口第三世代セフェム系抗菌薬の使用量の削減について

    東恩納 司, 岡崎 昌利, 稲葉 裕明, 飯尾 耕二, 筧 彩佳, 宮村 純子, 草野 展周, 塚原 宏一, 千堂 年昭

    日本環境感染学会総会プログラム・抄録集   35回   P5 - 7   2020年2月

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    記述言語:日本語   出版者・発行元:(一社)日本環境感染学会  

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  • VREのアウトブレイク事例とその解析

    筧 彩佳, 宮村 純子, 飯尾 耕治, 東恩納 司, 岡崎 昌利, 稲葉 裕明, 草野 展周, 塚原 宏一

    日本環境感染学会総会プログラム・抄録集   35回   P71 - 5   2020年2月

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    記述言語:日本語   出版者・発行元:(一社)日本環境感染学会  

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  • 起立性調節障害患者の背景因子についての検討

    藤井 智香子, 岡田 あゆみ, 鶴丸 靖子, 赤木 朋子, 重安 良恵, 山下 美保, 椙原 彰子, 堀内 真希子, 塚原 宏一

    子どもの心とからだ   28 ( 4 )   426 - 432   2020年2月

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    記述言語:日本語   出版者・発行元:(一社)日本小児心身医学会  

    起立性調節障害(orthostatic dysregulation:以下OD)の発症や経過には生活習慣、心理社会的要因が関与するといわれているが、具体的な報告は少ない。本研究では、OD患者の背景因子を検討し、その特徴を明らかにすることを目的として、岡山大学病院小児科においてODと診断した76例を対象に、背景因子を後方視的に検討した。結果、発達障害の併存を25例(32.9%)、うち自閉スペクトラム症を17例(22.4%)に認めた。また不登校を含め登校に何らかの困難を抱えた症例が67例(88.2%)で、34例(44.7%)が学校で友人関係や適応上の問題を認めており、17例(22.4%)の病前性格が過剰適応型だった。以上より、ODの発症や経過に心理社会的要因の影響を認めると推測され、約3割に発達障害を併存していることも踏まえて、心理社会的要因や発達特性に配慮した全人的治療が重要であると考えた。(著者抄録)

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  • 低カルシウム血症による痙攣で発症し、胸腺低形成が診断契機となった22q11.2欠失症候群の新生児例

    二川 奈都子, 長谷川 高誠, 塚原 宏一

    日本内分泌学会雑誌   95 ( 3 )   1171 - 1171   2020年1月

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    記述言語:日本語   出版者・発行元:(一社)日本内分泌学会  

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  • マルチターゲット療法で加療中,胃腸炎を機に急性腎障害に至った全身性エリテマトーデスの一例

    宮原宏幸, 石井雅人, 茂原研司, 津下充, 八代将登, 塚原宏一

    日本小児腎臓病学会雑誌(Web)   33 ( 1 )   2020年

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  • 起立性調節障害治療における学校連携に関するアンケート調査

    田中 知絵, 岡田 あゆみ, 赤木 朋子, 藤井 智香子, 重安 良恵, 椙原 彰子, 堀内 真希子, 塚原 宏一

    子どもの心とからだ   28 ( 3 )   337 - 337   2019年11月

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    記述言語:日本語   出版者・発行元:(一社)日本小児心身医学会  

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  • リストカット、大量服薬を認めた思春期女子の1例

    椙原 彰子, 藤井 智香子, 堀内 真希子, 田中 知絵, 赤木 朋子, 重安 良恵, 岡田 あゆみ, 塚原 宏一

    子どもの心とからだ   28 ( 3 )   340 - 340   2019年11月

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    記述言語:日本語   出版者・発行元:(一社)日本小児心身医学会  

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  • 難治性真菌感染症、慢性心不全、慢性腎不全を有する児に発症した関節型若年性特発性関節炎に対する治療アプローチ

    八代 将登, 茂原 研司, 藤井 洋輔, 斎藤 有希惠, 津下 充, 塚原 宏一

    日本小児リウマチ学会総会・学術集会プログラム・抄録集   29回   114 - 114   2019年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児リウマチ学会  

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  • 造血幹細胞移植施行患児における口腔内細菌叢の推移

    森川 優子, 吉田 衣里, 平野 慶子, 松三 友紀, 嶋田 明, 塚原 宏一, 仲野 道代

    日本小児血液・がん学会雑誌   56 ( 4 )   328 - 328   2019年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • 小児重症喘息に対するオマリズマブの有効性と効果予測因子の探索

    津下 充, 茂原 研司, 齋藤 有希惠, 八代 将登, 池田 政憲, 塚原 宏一

    日本小児アレルギー学会誌   33 ( 4 )   538 - 538   2019年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児アレルギー学会  

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  • ヒト脳血管内皮細胞を用いた高サイトカイン血症モデルにおけるhigh mobility group box 1抗体の血管透過性抑制効果

    津下 充, 難波 貴弘, 西堀 正洋, 斎藤 有希恵, 八代 将登, 塚原 宏一, 森島 恒雄

    日本小児感染症学会総会・学術集会プログラム・抄録集   51回   200 - 200   2019年10月

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    記述言語:日本語   出版者・発行元:日本小児感染症学会  

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  • 小児がん患者に対する口腔ケアの早期介入

    吉田 衣里, 森川 優子, 松三 友紀, 平野 慶子, 嶋田 明, 塚原 宏一, 仲野 道代

    日本小児血液・がん学会雑誌   56 ( 4 )   304 - 304   2019年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • 骨形成不全症の遺伝子解析と臨床像の検討

    樋口 洋介, 長谷川 高誠, 二川 奈都子, 山下 美保, 田中 弘之, 塚原 宏一

    日本内分泌学会雑誌   95 ( 2 )   707 - 707   2019年10月

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    記述言語:日本語   出版者・発行元:(一社)日本内分泌学会  

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  • 肺血管内皮細胞を用いたインフルエンザ重症肺炎モデルの構築とhigh mobility group box 1抗体による肺血管透過性亢進の抑制効果

    難波 貴弘, 津下 充, 西堀 正洋, 斎藤 有希恵, 八代 将登, 塚原 宏一, 森島 恒雄

    日本小児感染症学会総会・学術集会プログラム・抄録集   51回   133 - 133   2019年10月

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    記述言語:日本語   出版者・発行元:日本小児感染症学会  

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  • エトスクシミドにより誘発された膠原病類似疾患の検討

    茂原 研司, 八代 将登, 斎藤 有希惠, 津下 充, 塚原 宏一

    日本小児リウマチ学会総会・学術集会プログラム・抄録集   29回   88 - 88   2019年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児リウマチ学会  

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  • 起立性調節障害患者の酸化ストレス環境についての検討

    藤井 智香子, 津下 充, 岡田 あゆみ, 田中 知絵, 赤木 朋子, 重安 良恵, 椙原 彰子, 堀内 真希子, 塚原 宏一

    子どもの心とからだ   28 ( 2 )   260 - 260   2019年8月

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    記述言語:日本語   出版者・発行元:(一社)日本小児心身医学会  

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  • 心身症診療おけるP-Fスタディ(Picture Frustration Study)に関する研究 自閉スペクトラム症併存例の検討

    椙原 彰子, 岡田 あゆみ, 藤井 智香子, 重安 良恵, 赤木 朋子, 田中 知絵, 堀内 真希子, 塚原 宏一

    子どもの心とからだ   28 ( 2 )   271 - 271   2019年8月

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    記述言語:日本語   出版者・発行元:(一社)日本小児心身医学会  

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  • 神経発達症児に対する入院中の心理・発達支援に関する調査

    重安 良恵, 岡田 あゆみ, 椙原 彰子, 堀内 真希子, 田中 知絵, 赤木 朋子, 藤井 智香子, 塚原 宏一

    子どもの心とからだ   28 ( 2 )   259 - 259   2019年8月

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    記述言語:日本語   出版者・発行元:(一社)日本小児心身医学会  

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  • 精神発達遅滞を伴った小児にウルトラロングカテーテルを用いて腹膜透析を導入した1例

    宮井 貴之, 宮原 宏幸, 笠原 由美子, 野田 卓男, 塚原 宏一, 田中 弘之

    日本小児腎不全学会雑誌   39   250 - 252   2019年7月

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    記述言語:日本語   出版者・発行元:日本小児腎不全学会  

    精神発達遅滞を伴った小児には、身体にテープを貼られたりカテーテルを留置されたりすることを拒絶する者がおり、腹膜透析(peritoneal dialysis:PD)の導入に難渋することがある。成人領域では認知症を伴った高齢者に肩甲骨部出口でPDを導入する報告がある。精神発達遅滞を伴う末期腎不全の小児に対し、工夫してPDを導入した症例を報告する。ジュベール症候群の男児が15歳で末期腎不全に至りPDを行って献腎移植を待機する方針を選択した。出口部保清を保つため肩甲骨部出口を採用し、ウルトラロングカテーテルを留置し、良好な注排液が得られた。この2点の工夫が精神発達遅滞を伴った小児におけるPD導入時の問題を軽減し、これまで導入をあきらめていた例でもPDが腎代替療法の選択肢になりうることが示唆された。(著者抄録)

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  • 骨形成不全症の遺伝子解析と臨床像の検討

    樋口 洋介, 長谷川 高誠, 二川 奈都子, 山下 美保, 塚原 宏一

    日本内分泌学会雑誌   95 ( 1 )   391 - 391   2019年4月

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    記述言語:日本語   出版者・発行元:(一社)日本内分泌学会  

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  • 乳酸カルシウムの内服でくる病の改善を認めたビタミンD依存性くる病2A型の男児例

    長谷川 高誠, 二川 奈都子, 樋口 洋介, 塚原 宏一

    日本内分泌学会雑誌   95 ( 1 )   454 - 454   2019年4月

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    記述言語:日本語   出版者・発行元:(一社)日本内分泌学会  

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  • 病原体検索のための急性期検体採取に対する当院の取り組み

    八代 将登, 茂原 研司, 斎藤 有希惠, 藤井 洋輔, 津下 充, 塚原 宏一

    日本小児感染症学会総会・学術集会プログラム・抄録集   50回   162 - 162   2018年11月

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    記述言語:日本語   出版者・発行元:日本小児感染症学会  

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  • Failing Fontan患者におけるfenestration stentの有用性と中期予後について

    栗田 佳彦, 平井 健太, 重光 祐輔, 福嶋 遥祐, 近藤 麻衣子, 馬場 健児, 大月 審一, 塚原 宏一, 笠原 慎吾

    日本小児循環器学会雑誌   34 ( Suppl.1 )   s1 - 229   2018年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本小児循環器学会  

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  • 閉鎖困難が予想された心室中隔欠損に対するCT評価の有用性について

    栗田 佳彦, 大月 審一, 平井 健太, 重光 祐輔, 栄徳 隆裕, 近藤 麻衣子, 馬場 健児, 塚原 宏一, 佐野 俊二, 笠原 慎吾

    日本小児循環器学会雑誌   33 ( Suppl.1 )   s1 - 344   2017年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本小児循環器学会  

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  • OFD1ヘミ接合性ミスセンス変異を認めたネフロン癆関連シリオパチーの1男児例

    清水 順也, 森貞 直哉, 飯島 一誠, 神農 陽子, 城 謙輔, 竹村 司, 久保 俊英, 塚原 宏一

    日本小児腎臓病学会雑誌   30 ( 1Suppl. )   214 - 214   2017年5月

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    記述言語:日本語   出版者・発行元:(一社)日本小児腎臓病学会  

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  • 新生児・乳児ビタミンK欠乏性出血症に対するビタミンK製剤投与の改訂ガイドライン(修正版) (特集 助産師が押さえておきたいガイドライン : エビデンスに基づいたケアを実践するために)

    鷲尾 洋介, 岡村 朋香, 塚原 宏一

    ペリネイタルケア   35 ( 11 )   1088 - 1091   2016年11月

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    記述言語:日本語   出版者・発行元:メディカ出版  

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    その他リンク: http://search.jamas.or.jp/link/ui/2017079430

  • 右室流出路再建術にContegraを使用した18症例の検討

    平井 健太, 馬場 健児, 近藤 麻衣子, 栗田 佳彦, 栄徳 隆裕, 福嶋 遥佑, 重光 祐輔, 大月 審一, 笠原 真悟, 佐野 俊二, 塚原 宏一

    日本小児循環器学会雑誌   32 ( Suppl.1 )   s1 - 216   2016年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本小児循環器学会  

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  • 二心室治療可能であった左心系低形成症例について

    栗田 佳彦, 大月 審一, 平井 健太, 重光 祐輔, 福嶋 遥佑, 栄徳 隆裕, 近藤 麻衣子, 馬場 健児, 塚原 宏一, 佐野 俊二, 岩崎 達雄

    日本小児循環器学会雑誌   32 ( Suppl.1 )   s1 - 184   2016年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本小児循環器学会  

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  • 中国四国地区における急性弛緩性麻痺を認める症例の網羅的調査

    八代 将登, 藤井 洋輔, 山下 信子, 塚原 宏一, 多屋 馨子, 森島 恒雄

    臨床とウイルス   44 ( 2 )   S61 - S61   2016年5月

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    記述言語:日本語   出版者・発行元:日本臨床ウイルス学会  

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  • レドックス制御蛋白チオレドキシン(TRX)のインフルエンザ肺炎における治療的効果

    八代 将登, 野坂 宜之, 藤井 洋輔, 斎藤 有希惠, 山下 信子, 山田 雅夫, 塚原 宏一, 森島 恒雄

    臨床とウイルス   43 ( 2 )   S80 - S80   2015年5月

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    記述言語:日本語   出版者・発行元:日本臨床ウイルス学会  

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  • 急性脳症患者におけるCOX-2のDNAメチル化の関与

    藤井 洋輔, 齋藤 有希惠, 野坂 宜之, 八代 将登, 山下 信子, 塚原 宏一, 森島 恒雄

    日本小児科学会雑誌   118 ( 2 )   269 - 269   2014年2月

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    記述言語:日本語   出版者・発行元:(公社)日本小児科学会  

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  • Multiple biomarkers for oxidative stress in patients with brain disorders

    Hirokazu Tsukahara, Yosuke Fujii, Yuko Hayashi, Tsuneo Morishima

    Journal of the Neurological Sciences   313 ( 1-2 )   196   2012年2月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)  

    DOI: 10.1016/j.jns.2011.10.014

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  • インフルエンザ脳症など重症インフルエンザの発症機序の解明とそれに基づく治療法,予防法の確立に関する研究 生体マーカーを用いた脳炎・脳症患者の病態評価

    塚原宏一, 藤井洋輔, 山田睦子, 斎藤有希恵, 長岡義晴, 津下充, 森島恒雄, 市山高志, 松原康策, 毎原敏郎, 羽田敦子, 梶俊策, 後藤振一郎

    インフルエンザ脳症など重症インフルエンザの発症機序の解明とそれに基づく治療法、予防法の確立に関する研究 平成23年度 総合・分担研究報告書   2012年

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  • 早産極低出生体重児にビタミンD蓄積・骨ミネラル代謝に対する混合栄養の有用性についての検討

    菊池 尚子, 塚原 宏一, 徳力 周子, 川谷 正男, 畑 郁江, 眞弓 光文, 大嶋 勇成

    小児科臨床   65 ( 5 )   1051 - 1056   2012年

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  • Evaluation of oxidative stress status in children with pervasive developmental disorder and attention deficit hyperactivity disorder using urinary-specific biomarkers

    M.Kawatani, H.Tsukahara, M.Mayumi

    Redox Report   16 ( 1 )   45 - 46   2011年

  • Favorable effect of 4-phenylacetate on liver functions attributable to enhanced bile salt export pump expression in ornithine transcarbamylase-deficient children

    Hironori Nagasaka, Tohru Yorifuji, Kunihiko Kobayashi, Hajime Takikawa, Haruki Komatsu, Ayano Inui, Tomoo Fujisawa, Takashi Miida, Hirokazu Tsukahara, Tomozumi Takatani, Hisamitsu Hayashi

    MOLECULAR GENETICS AND METABOLISM   100 ( 2 )   123 - 128   2010年6月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    4-Phenylbutyrate (4-PB) acting against hyperammonemia has been administered to patients with urea cycle defects. Results of our recent experiments using animals and cultured cells strongly suggest that this agent enhances the function of bile salt export pump/ATP binding cassette B11 (BSEP/ABCB11) promoting bile acid excretion from hepatocytes to bile canaliculi, although it has not been confirmed in humans. Considering that 4-PB is converted easily into 4-phenylacetate (4-PA) in the liver, such an effect of 4-PB might occur through 4-PA. We performed retrospective analyzes of the effects of 4-PA on the liver functions of three ornithine transcarbamylase (OTC)-deficient female children receiving 4-PA. Two of the three received intravenous administration of 4-PA only at episodic periods of hyperammonemia; the remaining one received it orally at intercurrent periods. Soon after 4-PA administration, the serum total bile acid level was decreased to one-half or one-third of pre-treatment levels, but it returned to the basal levels within one month after 4-PA discontinuation. Other serum parameters for cholestasis such as gamma-glutamyl transferase also decreased markedly. Concomitantly, alanine aminotransferase and aspartate amino transferase levels decreased significantly. Western blot analyzes of the liver samples revealed that the 4-PA administration enhanced BSEP/ABCB11 protein expressions in the membranous fraction of liver cells, although the liver BSEP/ABCB11 messenger RNA level remained unchanged. These results suggest that 4-PA enhanced liver BSEP/ABCB11 function and thereby improved liver functions in OTC-deficient children. For treatment of liver disorders requiring enhancement of BSEP function, 4-PA might be a candidate. (C) 2010 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.ymgme.2010.02.008

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  • On Being a Resident and a Mom

    Koji Nishijima, Jin Takahashi, Makoto Yamamoto, Makoto Orisaka, Chiyo Suzuki, Hirokazu Tsukahara, Ken-ichi Shukunami, Tetsuji Kurokawa, Yoshio Yoshida, Fumikazu Kotsuji

    ANNALS OF EMERGENCY MEDICINE   55 ( 5 )   483 - +   2010年5月

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    記述言語:英語   出版者・発行元:MOSBY-ELSEVIER  

    DOI: 10.1016/j.annemergmed.2009.06.506

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  • Detection of cytomegalovirus in preserved umbilical cord from a boy with autistic disorder

    Masao Kawatani, Akio Nakai, Takashi Okuno, Ritsuyo Kobata, Masako Moriuchi, Hiroyuki Moriuchi, Hirokazu Tsukahara, Mitsufumi Mayumi

    PEDIATRICS INTERNATIONAL   52 ( 2 )   304 - 307   2010年4月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    DOI: 10.1111/j.1442-200X.2010.03027.x

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  • Detection of cytomegalovirus in preserved umbilical cord from a boy with autistic disorder

    Masao Kawatani, Akio Nakai, Takashi Okuno, Ritsuyo Kobata, Masako Moriuchi, Hiroyuki Moriuchi, Hirokazu Tsukahara, Mitsufumi Mayumi

    PEDIATRICS INTERNATIONAL   52 ( 2 )   304 - 307   2010年4月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    DOI: 10.1111/j.1442-200X.2010.03027.x

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  • Coupling of the citrulline recycling to endothelial NO production

    Hirokazu Tsukahara, Hironori Nagasaka, Shuko Tokuriki, Mitsufumi Mayumi

    MOLECULAR GENETICS AND METABOLISM   99 ( 4 )   438 - 438   2010年4月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    DOI: 10.1016/j.ymgme.2009.11.009

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  • Coupling of the citrulline recycling to endothelial NO production

    Hirokazu Tsukahara, Hironori Nagasaka, Shuko Tokuriki, Mitsufumi Mayumi

    MOLECULAR GENETICS AND METABOLISM   99 ( 4 )   438 - 438   2010年4月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    DOI: 10.1016/j.ymgme.2009.11.009

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  • Asymmetric dimethylarginine, an endogenous NO synthase inhibitor, in human breast milk

    Hirokazu Tsukahara, Hironori Nagasaka

    EARLY HUMAN DEVELOPMENT   86 ( 2 )   69 - 70   2010年2月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.earlhumdev.2010.01.021

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  • Asymmetric dimethylarginine, an endogenous NO synthase inhibitor, in human breast milk

    Hirokazu Tsukahara, Hironori Nagasaka

    EARLY HUMAN DEVELOPMENT   86 ( 2 )   69 - 70   2010年2月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.earlhumdev.2010.01.021

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  • Altered metabolisms of mediators controlling vascular function and enhanced oxidative stress in asymptomatic children with congenital portosystemic venous shunt

    Hironori Nagasaka, Yoshiyuki Okano, Madoka Aizawa, Takashi Miida, Tohru Yorifuji, Go Tajima, Nobuo Sakura, Tomozumi Takatani, Yoshitami Sanayama, Kenji Sugamoto, Mitsufumi Mayumi, Kunihiko Kobayashi, Kenichi Hirano, Masaki Takayanagi, Hirokazu Tsukaharah

    METABOLISM-CLINICAL AND EXPERIMENTAL   59 ( 1 )   107 - 113   2010年1月

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    記述言語:英語   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    Children with congenital portosystemic venous shunt (PSVS) are at risk for developing pulmonary hypertension, irrespective of the severity of portal hypertension or liver damage. Altered metabolisms of nitric oxide (NO) and endothelin-1 (ET-1), which are linked with oxidative stress and control vascular tone, might contribute to the vascular disturbance. This study examined 14 children (aged 1-5 years) with congenital PSVS lacking major liver damage and portal hypertension. Serum levels of nitrite/nitrate (NOx) as stable metabolites of NO, and of asymmetric dimethylarginine (ADMA) as an endogenous NO synthase inhibitor were determined, along with the plasma level of ET-1. Oxidative stress, which might affect the production of such mediators, was also examined using specific urinary and blood markers. The NOx levels were significantly lower in affected children than in the age-matched control group, although ET-1 levels were significantly higher than the control levels. In the affected children, the ADMA levels and ADMA/NOx ratios were higher, respectively, by 30% and 130% and showed significant positive correlations with the shunt ratios. Oxidative stress markers, including plasma thiobarbiturate reactive substances and urinary acrolein-lysine and 8-hydroxy-2'-deoxyguanosine, were significantly higher in affected children than in the control group, consistent with them being subjected to enhanced oxidative stress. These results suggest the presence of altered metabolisms of vascular mediators and enhanced oxidative stress in asymptomatic preschool children with congenital PSVS. (C) 2010 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.metabol.2009.07.013

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  • Altered metabolisms of mediators controlling vascular function and enhanced oxidative stress in asymptomatic children with congenital portosystemic venous shunt

    Hironori Nagasaka, Yoshiyuki Okano, Madoka Aizawa, Takashi Miida, Tohru Yorifuji, Go Tajima, Nobuo Sakura, Tomozumi Takatani, Yoshitami Sanayama, Kenji Sugamoto, Mitsufumi Mayumi, Kunihiko Kobayashi, Kenichi Hirano, Masaki Takayanagi, Hirokazu Tsukaharah

    METABOLISM-CLINICAL AND EXPERIMENTAL   59 ( 1 )   107 - 113   2010年1月

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    記述言語:英語   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    Children with congenital portosystemic venous shunt (PSVS) are at risk for developing pulmonary hypertension, irrespective of the severity of portal hypertension or liver damage. Altered metabolisms of nitric oxide (NO) and endothelin-1 (ET-1), which are linked with oxidative stress and control vascular tone, might contribute to the vascular disturbance. This study examined 14 children (aged 1-5 years) with congenital PSVS lacking major liver damage and portal hypertension. Serum levels of nitrite/nitrate (NOx) as stable metabolites of NO, and of asymmetric dimethylarginine (ADMA) as an endogenous NO synthase inhibitor were determined, along with the plasma level of ET-1. Oxidative stress, which might affect the production of such mediators, was also examined using specific urinary and blood markers. The NOx levels were significantly lower in affected children than in the age-matched control group, although ET-1 levels were significantly higher than the control levels. In the affected children, the ADMA levels and ADMA/NOx ratios were higher, respectively, by 30% and 130% and showed significant positive correlations with the shunt ratios. Oxidative stress markers, including plasma thiobarbiturate reactive substances and urinary acrolein-lysine and 8-hydroxy-2'-deoxyguanosine, were significantly higher in affected children than in the control group, consistent with them being subjected to enhanced oxidative stress. These results suggest the presence of altered metabolisms of vascular mediators and enhanced oxidative stress in asymptomatic preschool children with congenital PSVS. (C) 2010 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.metabol.2009.07.013

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  • 内科疾患の診断基準・病型分類・重症度: 先天性ネフローゼ症候群

    塚原 宏一

    内科(in press)   2010年

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  • 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. 最終回: 追加・補足事項 - 薬物療法から精神疾患まで

    塚原 宏一, 塚原 康代

    内科   105 ( 2 )   318 - 323   2010年

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  • 書評: 小児・新生児診療ゴールデンハンドブック(旭川医科大学小児科学講座 藤枝憲二, 梶野浩樹編著). 小児医療の安全ルートを指し示すガイドブック

    塚原 宏一

    内科   105 ( 3 )   530   2010年

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  • 早産低出生体重児の生体環境偏移の長期評価とその対策: 「成人病胎児期発症説」の検証

    塚原 宏一

    平成21年度科学研究費補助金実績報告書(基盤研究C)   2010年

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  • 小児科領域における一酸化窒素および酸化ストレスに関連する生体マーカーの現況

    塚原 宏一, 眞弓 光文, 長坂博範

    発達腎研究会誌   2010年

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  • ホタル(火垂る)物語とMitochondriaそしてNO、REDOX

    塚原 宏一

    発達腎研究会誌   2010年

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  • 先天性代謝疾患と一酸化窒素、酸化ストレス.

    長坂 博範, 塚原 宏一

    発達腎研究会誌   2010年

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  • 内科疾患の診断基準・病型分類・重症度: 溶血性尿毒症症候群

    塚原 宏一

    内科(in press)   2010年

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  • 内科疾患の診断基準・病型分類・重症度: Alport症候群

    塚原 宏一

    内科(in press)   2010年

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  • 内科疾患の診断基準・病型分類・重症度: 先天性ネフローゼ症候群

    塚原 宏一

    内科(in press)   2010年

     詳細を見る

  • 胎児・新生児の成長と骨

    塚原 宏一

    骨粗鬆症治療   2010年

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  • 母乳中の生理活性因子の生物学的・治療学的意義

    塚原 宏一

    平成20年度総合健康推進財団研究助成成果報告書 (in press)   2010年

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  • 先天代謝異常症における一酸化窒素代謝系の病態学的意義の探索: 新規の予防・治療法の開発に向けて

    塚原 宏一, 徳力 周子, 田村 知史, 川谷 正男, 畑 郁江, 大嶋 勇成, 西島 浩二

    福井大学重点研究成果集 (in press)   2010年

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  • 極低出生体重児のビタミンD蓄積および骨ミネラル代謝の評価

    巨田 尚子, 塚原 宏一, 徳力 周子, 小倉 一将, 川谷 正男, 畑 郁江, 眞弓 光文

    第27回代謝性骨疾患研究会発表論文集 (in press)   2010年

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  • 小児における二重エネルギーX線吸収測定法を用いた骨塩定量の論文報告の総括

    塚原 宏一

    平成21年度腎不全病態研究助成成果報告書   2010年

     詳細を見る

  • 胎児・新生児の成長と骨

    塚原 宏一

    骨粗鬆症治療   2010年

     詳細を見る

  • 母乳中の生理活性因子の生物学的・治療学的意義

    塚原 宏一

    平成20年度総合健康推進財団研究助成成果報告書 (in press)   2010年

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  • インフルエンザ脳症の発症におけるレドックスの役割と治療への応用

    塚原 宏一

    平成21年度厚生労働科学研究費補助金(新型インフルエンザ等新興・再興感染症研究事業)分担研究報告書: インフルエンザ脳症など重症インフルエンザの発症機序の解明とそれに基づく治療法・予防法の確立に関する研究(主任研究者 森島恒雄   2010年

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  • 先天代謝異常症における一酸化窒素代謝系の病態学的意義の探索: 新規の予防・治療法の開発に向けて

    塚原 宏一, 徳力 周子, 田村 知史, 川谷 正男, 畑 郁江, 大嶋 勇成, 西島 浩二

    福井大学重点研究成果集 (in press)   2010年

     詳細を見る

  • 極低出生体重児のビタミンD蓄積および骨ミネラル代謝の評価

    巨田 尚子, 塚原 宏一, 徳力 周子, 小倉 一将, 川谷 正男, 畑 郁江, 眞弓 光文

    第27回代謝性骨疾患研究会発表論文集 (in press)   2010年

     詳細を見る

  • 小児における二重エネルギーX線吸収測定法を用いた骨塩定量の論文報告の総括

    塚原 宏一

    平成21年度腎不全病態研究助成成果報告書   2010年

     詳細を見る

  • 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. 最終回: 追加・補足事項 - 薬物療法から精神疾患まで

    塚原 宏一, 塚原 康代

    内科   105 ( 2 )   318 - 323   2010年

     詳細を見る

  • 書評: 小児・新生児診療ゴールデンハンドブック(旭川医科大学小児科学講座 藤枝憲二, 梶野浩樹編著). 小児医療の安全ルートを指し示すガイドブック

    塚原 宏一

    内科   105 ( 3 )   530   2010年

     詳細を見る

  • 早産低出生体重児の生体環境偏移の長期評価とその対策: 「成人病胎児期発症説」の検証

    塚原 宏一

    平成21年度科学研究費補助金実績報告書(基盤研究C)   2010年

     詳細を見る

  • 小児科領域における一酸化窒素および酸化ストレスに関連する生体マーカーの現況

    塚原 宏一, 眞弓 光文, 長坂博範

    発達腎研究会誌   2010年

     詳細を見る

  • ホタル(火垂る)物語とMitochondriaそしてNO、REDOX

    塚原 宏一

    発達腎研究会誌   2010年

     詳細を見る

  • 先天性代謝疾患と一酸化窒素、酸化ストレス.

    長坂 博範, 塚原 宏一

    発達腎研究会誌   2010年

     詳細を見る

  • 内科疾患の診断基準・病型分類・重症度: 溶血性尿毒症症候群

    塚原 宏一

    内科(in press)   2010年

     詳細を見る

  • 内科疾患の診断基準・病型分類・重症度: Alport症候群

    塚原 宏一

    内科(in press)   2010年

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  • Ureaplasma urealyticum感染が病因と考えられ、呼吸管理に難渋したWilson-Mikity症候群の1例

    徳力 周子, 五十嵐 愛子, 菊地 尚子, 田村 知史, 畑 郁江, 塚原 宏一, 眞弓 光文, 高橋 仁, 西島 浩二, 小辻 文和, 長谷川 妙子, 小出 亜希子, 柳原 格, 佐々木 裕子, 見理 剛

    日本小児科学会雑誌   113 ( 12 )   1867 - 1867   2009年12月

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    記述言語:日本語   出版者・発行元:(公社)日本小児科学会  

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  • HYPERCITRULLINEMIA, HYPERCHOLESTEROLEMIA AND AUGMENTED OXIDATIVE STRESS IN THE PATIENTS WITH CITRIN DEFICIENCY DURING THE SILENT PERIOD

    Y. Okano, H. Nagasaka, Y. Shigematsu, H. Tsukahara, T. Momoi, T. Yorifuji, T. Ohura, T. Miida, K. Hirano, K. Kobayashi, T. Saheki, M. Takayanagi

    MOLECULAR GENETICS AND METABOLISM   98 ( 1-2 )   10 - 10   2009年9月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

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  • ALTERED METABOLISMS OF MEDIATORS CONTROLLING VASCULAR FUNCTION AND EVIDENCE OF OXIDATIVE STRESS IN ASYMPTOMATIC CHILDREN WITH CONGENITAL PORTOSYSTEMIC VENOUS SHUNT

    H. Nagasaka, Y. Okano, H. Tsukahara

    MOLECULAR GENETICS AND METABOLISM   98 ( 1-2 )   110 - 110   2009年9月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

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  • Lipoprotein profiles in children with two common cholesteryl ester transfer protein gene mutations, D442G and I14A, during the first year of life

    Hironori Nagasaka, Tohru Yorifuji, Toru Momoi, Junko Yorifuji, Kenichi Hirano, Akemi Ota, Tomozumi Takatani, Hirokazu Tsukahara, Masaki Takayanagi, Kunihiko Kobayashi, Hitoshi Chiba, Yukiyasu Sato, Takashi Miida

    CLINICA CHIMICA ACTA   406 ( 1-2 )   52 - 56   2009年8月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    Background: Hyperalphalipoproteinemia is associated with cholesteryl ester transfer protein (CETP) deficiency in adults but has unclear associations in children.
    Methods: We measured lipoproteins in 19 heterozygotes (D442G, n = 17; I14A, n = 2), one D442G/I14A compound heterozygote, 13 non-affected siblings, and 30 healthy controls at birth, 3-4 months, and 12 months.
    Results: CETP mass was 32-70% lower in heterozygotes than in controls throughout the year. Low-density lipoprotein-cholesterol (LDL-C) was lower in heterozygotes than in controls by 30, 20, and 15% at birth, 34 months, and 12 months, respectively. High-density lipoprotein-cholesterol (HDL-C) was similar among the groups at birth, but was 10% higher in heterozygotes compared with controls at 3-4 and 12 months. ApoE-rich HDL-C was similar between the two groups at birth, but was 50% higher in heterozygotes than in controls at 3-4 and 12 months. These lipoprotein profile characteristics were prominent in the compound heterozygote but were not found in non-affected siblings. In heterozygotes. CETP mass correlated positively with LDL-C but negatively with HDL-C at 3-4 and 12 months.
    Conclusion: CETP is a determinant for LDL-C and HDL-C in CETP-deficient individuals in the first year of life. (C) 2009 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.cca.2009.05.007

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  • Lipoprotein profiles in children with two common cholesteryl ester transfer protein gene mutations, D442G and I14A, during the first year of life

    Hironori Nagasaka, Tohru Yorifuji, Toru Momoi, Junko Yorifuji, Kenichi Hirano, Akemi Ota, Tomozumi Takatani, Hirokazu Tsukahara, Masaki Takayanagi, Kunihiko Kobayashi, Hitoshi Chiba, Yukiyasu Sato, Takashi Miida

    CLINICA CHIMICA ACTA   406 ( 1-2 )   52 - 56   2009年8月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    Background: Hyperalphalipoproteinemia is associated with cholesteryl ester transfer protein (CETP) deficiency in adults but has unclear associations in children.
    Methods: We measured lipoproteins in 19 heterozygotes (D442G, n = 17; I14A, n = 2), one D442G/I14A compound heterozygote, 13 non-affected siblings, and 30 healthy controls at birth, 3-4 months, and 12 months.
    Results: CETP mass was 32-70% lower in heterozygotes than in controls throughout the year. Low-density lipoprotein-cholesterol (LDL-C) was lower in heterozygotes than in controls by 30, 20, and 15% at birth, 34 months, and 12 months, respectively. High-density lipoprotein-cholesterol (HDL-C) was similar among the groups at birth, but was 10% higher in heterozygotes compared with controls at 3-4 and 12 months. ApoE-rich HDL-C was similar between the two groups at birth, but was 50% higher in heterozygotes than in controls at 3-4 and 12 months. These lipoprotein profile characteristics were prominent in the compound heterozygote but were not found in non-affected siblings. In heterozygotes. CETP mass correlated positively with LDL-C but negatively with HDL-C at 3-4 and 12 months.
    Conclusion: CETP is a determinant for LDL-C and HDL-C in CETP-deficient individuals in the first year of life. (C) 2009 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.cca.2009.05.007

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  • Sustaining hypercitrullinemia, hypercholesterolemia and augmented oxidative stress in Japanese children with aspartate/glutamate carrier isoform 2-citrin-deficiency even during the silent period

    Hironori Nagasaka, Yoshiyuki Okano, Hirokazu Tsukahara, Yosuke Shigematsu, Toru Momoi, Junko Yorifuji, Takashi Miida, Toshihiro Ohura, Keiko Kobayashi, Takeyori Saheki, Kenichi Hirano, Masaki Takayanagi, Tohru Yorifuji

    MOLECULAR GENETICS AND METABOLISM   97 ( 1 )   21 - 26   2009年5月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) shows diverse metabolic abnormalities such as urea cycle dysfunction together with citrullinemia, galactosemia, and suppressed gluconeogenesis. Such abnormalities apparently resolve during the first year of life. However, metabolic profiles of the silent period remain unknown. We analyzed oxidative stress markers and profiles of amino acids, carbohydrates, and lipids in 20 asymptomatic children with aspartate/glutamate carrier isoform 2-citrin-deficiency aged 1-10 years, for whom tests showed normal liver function. Despite normal plasma ammonia levels, the affected children showed higher blood levels of ornithine (p &lt; 0.001) and citrulline (p &lt; 0.01)-amino acids involved in the urea cycle-than healthy children. Blood levels of nitrite/nitrate, metabolites of nitric oxide (NO), and asymmetric dimethylarginine inhibiting NO production from arginine were not different between these two groups. Blood glucose, galactose, pyruvate, and lactate levels after 4-5 h fasting were not different between these groups, but the affected group showed a significantly higher lactate to pyruvate ratio. Low-density and high-density lipoprotein cholesterol levels in the affected group were 1.5 times higher than those in the controls. Plasma oxidized low-density lipoprotein apparently increased in the affected children; their levels of urinary oxidative stress markers such as 8-hydroxy-2'-deoxyguanosine and acrolein-lysine were significantly higher than those in the controls. Results of this study showed, even during the silent period, sustained hypercitrullinemia, hypercholesterolemia, and augmented oxidative stress in children with citrin deficiency. (C) 2009 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.ymgme.2009.01.009

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  • Sustaining hypercitrullinemia, hypercholesterolemia and augmented oxidative stress in Japanese children with aspartate/glutamate carrier isoform 2-citrin-deficiency even during the silent period

    Hironori Nagasaka, Yoshiyuki Okano, Hirokazu Tsukahara, Yosuke Shigematsu, Toru Momoi, Junko Yorifuji, Takashi Miida, Toshihiro Ohura, Keiko Kobayashi, Takeyori Saheki, Kenichi Hirano, Masaki Takayanagi, Tohru Yorifuji

    MOLECULAR GENETICS AND METABOLISM   97 ( 1 )   21 - 26   2009年5月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) shows diverse metabolic abnormalities such as urea cycle dysfunction together with citrullinemia, galactosemia, and suppressed gluconeogenesis. Such abnormalities apparently resolve during the first year of life. However, metabolic profiles of the silent period remain unknown. We analyzed oxidative stress markers and profiles of amino acids, carbohydrates, and lipids in 20 asymptomatic children with aspartate/glutamate carrier isoform 2-citrin-deficiency aged 1-10 years, for whom tests showed normal liver function. Despite normal plasma ammonia levels, the affected children showed higher blood levels of ornithine (p &lt; 0.001) and citrulline (p &lt; 0.01)-amino acids involved in the urea cycle-than healthy children. Blood levels of nitrite/nitrate, metabolites of nitric oxide (NO), and asymmetric dimethylarginine inhibiting NO production from arginine were not different between these two groups. Blood glucose, galactose, pyruvate, and lactate levels after 4-5 h fasting were not different between these groups, but the affected group showed a significantly higher lactate to pyruvate ratio. Low-density and high-density lipoprotein cholesterol levels in the affected group were 1.5 times higher than those in the controls. Plasma oxidized low-density lipoprotein apparently increased in the affected children; their levels of urinary oxidative stress markers such as 8-hydroxy-2'-deoxyguanosine and acrolein-lysine were significantly higher than those in the controls. Results of this study showed, even during the silent period, sustained hypercitrullinemia, hypercholesterolemia, and augmented oxidative stress in children with citrin deficiency. (C) 2009 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.ymgme.2009.01.009

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  • Evaluation of endogenous nitric oxide synthesis in congenital urea cycle enzyme defects

    Hironori Nagasaka, Hirokazu Tsukahara, Tohru Yorifuji, Takashi Miida, Kei Murayama, Tomoko Tsuruoka, Tomozumi Takatani, Masaki Kanazawa, Kunihiko Kobayashi, Yoshiyuki Okano, Masaki Takayanagi

    METABOLISM-CLINICAL AND EXPERIMENTAL   58 ( 3 )   278 - 282   2009年3月

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    記述言語:英語   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    Nitric oxide (NO) is synthesized from arginine and O-2 by nitric oxide synthase (NOS). Citrulline, which is formed as a by-product of the NOS reaction, can be recycled to arginine by the 2 enzymes acting in the urea cycle: argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL). Although the complete Urea cycle is expressed only in the liver, ASS and ASL are expressed in other organs including the kidney and vascular endothelium. To examine possible alterations of the NO pathway in urea cycle defects, we measured plasma concentrations of arginine and citrulline and serum concentrations of nitrite/nitrate (NOx(-), stable NO metabolites) and asymmetric dimethylarginine (ADMA, an endogenous NOS inhibitor) in patients with congenital urea cycle disorders of 3 types: ornithine transcarbamylase (OTC) deficiency, ASS deficiency, and ASL deficiency. All were receiving oral arginine replacement at the time of this study. The same parameters were also measured in healthy subjects, who participated as controls. The OTC-deficient patients had significantly high NOx(-) and nonsignificantly high ADMA concentrations. Their NOx(-) was significantly positively correlated with arginine. The ASS-deficient patients had significantly low NOx(-) and significantly high ADMA concentrations. The ASL-deficient patients had normal NOx(-) and nonsignificantly high ADMA concentrations. In ASS-deficient and ASL-deficient patients, the NOx(-) was significantly inversely correlated with citrulline, These results suggest that NO synthesis is enhanced in OTC-deficient patients while receiving arginine but that NO synthesis remains low in ASS-deficient patients despite receiving arginine. They also suggest that endogenous NO synthesis is negatively affected by citrulline and ADMA in ASS-deficient and ASL-deficient patients. Although the molecular mechanisms remain poorly understood, we infer that the NO pathway might play a role in the pathophysiology related to congenital urea cycle disorders. (C) 2009 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.metabol.2008.09.025

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  • Evaluation of endogenous nitric oxide synthesis in congenital urea cycle enzyme defects

    Hironori Nagasaka, Hirokazu Tsukahara, Tohru Yorifuji, Takashi Miida, Kei Murayama, Tomoko Tsuruoka, Tomozumi Takatani, Masaki Kanazawa, Kunihiko Kobayashi, Yoshiyuki Okano, Masaki Takayanagi

    METABOLISM-CLINICAL AND EXPERIMENTAL   58 ( 3 )   278 - 282   2009年3月

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    記述言語:英語   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    Nitric oxide (NO) is synthesized from arginine and O-2 by nitric oxide synthase (NOS). Citrulline, which is formed as a by-product of the NOS reaction, can be recycled to arginine by the 2 enzymes acting in the urea cycle: argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL). Although the complete Urea cycle is expressed only in the liver, ASS and ASL are expressed in other organs including the kidney and vascular endothelium. To examine possible alterations of the NO pathway in urea cycle defects, we measured plasma concentrations of arginine and citrulline and serum concentrations of nitrite/nitrate (NOx(-), stable NO metabolites) and asymmetric dimethylarginine (ADMA, an endogenous NOS inhibitor) in patients with congenital urea cycle disorders of 3 types: ornithine transcarbamylase (OTC) deficiency, ASS deficiency, and ASL deficiency. All were receiving oral arginine replacement at the time of this study. The same parameters were also measured in healthy subjects, who participated as controls. The OTC-deficient patients had significantly high NOx(-) and nonsignificantly high ADMA concentrations. Their NOx(-) was significantly positively correlated with arginine. The ASS-deficient patients had significantly low NOx(-) and significantly high ADMA concentrations. The ASL-deficient patients had normal NOx(-) and nonsignificantly high ADMA concentrations. In ASS-deficient and ASL-deficient patients, the NOx(-) was significantly inversely correlated with citrulline, These results suggest that NO synthesis is enhanced in OTC-deficient patients while receiving arginine but that NO synthesis remains low in ASS-deficient patients despite receiving arginine. They also suggest that endogenous NO synthesis is negatively affected by citrulline and ADMA in ASS-deficient and ASL-deficient patients. Although the molecular mechanisms remain poorly understood, we infer that the NO pathway might play a role in the pathophysiology related to congenital urea cycle disorders. (C) 2009 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.metabol.2008.09.025

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  • Effects of bezafibrate on dyslipidemia with cholestasis in children with familial intrahepatic cholestasis-1 deficiency manifesting progressive familial intrahepatic cholestasis

    Hironori Nagasaka, Tohru Yorifuji, Kenichi Hirano, Akemi Otac, Yumiko Toyama-Nakagawa, Tomozumi Takatani, Hirokazu Tsukahara, Kunihiko Kobayashi, Masaki Takayanagi, Yukihiro Inomata, Shinji Uemoto, Takashi Miida

    METABOLISM-CLINICAL AND EXPERIMENTAL   58 ( 1 )   48 - 54   2009年1月

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    記述言語:英語   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    No appropriate pharmaceutical therapy has been established for dyslipidemia with cholestasis in progressive familial intrahepatic cholestasis(PFIC)-1. We evaluated the efficacy of bezafibrate in PFIC-1. We monitored the clinical presentation and lipoprotein metabolism of 3 patients, aged 3, 4, and 8 years. with FIC1 deficiency, manifesting PFIC-1, over 12 months of bezafibrate therapy. Pruritus was substantially alleviated in the 3 patients after initiation of bezafibrate. Cholestasis was alleviated in 2 of them. Serum high-density lipoprotein cholesterol and low-density lipoprotein cholesterol increased 1.6- to 2.0-fold and 1.1 - to 1.2-fold, respectively; but the values remained low and normal, respectively. Serum lipoprotein X, which was at normal levels before treatment, was elevated to levels above the upper limit of the reference range. High serum triglyceride levels decreased by 15% to 30%, to normal levels, after treatment initiation. The activities of lipoprotein lipase and hepatic triglyceride lipase were increased, but those of high-density lipoprotein regulators remained unchanged. Liver expression Of multidrug resistance protein-3, which regulates lipoprotein X synthesis, was enhanced by bezafibrate therapy. Bezafibrate treatment favorably affected pruritus, dyslipidemia, and cholestasis in PFIC-1. (C) 2009 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.metabol.2008.08.005

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  • Effects of bezafibrate on dyslipidemia with cholestasis in children with familial intrahepatic cholestasis-1 deficiency manifesting progressive familial intrahepatic cholestasis

    Hironori Nagasaka, Tohru Yorifuji, Kenichi Hirano, Akemi Otac, Yumiko Toyama-Nakagawa, Tomozumi Takatani, Hirokazu Tsukahara, Kunihiko Kobayashi, Masaki Takayanagi, Yukihiro Inomata, Shinji Uemoto, Takashi Miida

    METABOLISM-CLINICAL AND EXPERIMENTAL   58 ( 1 )   48 - 54   2009年1月

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    記述言語:英語   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    No appropriate pharmaceutical therapy has been established for dyslipidemia with cholestasis in progressive familial intrahepatic cholestasis(PFIC)-1. We evaluated the efficacy of bezafibrate in PFIC-1. We monitored the clinical presentation and lipoprotein metabolism of 3 patients, aged 3, 4, and 8 years. with FIC1 deficiency, manifesting PFIC-1, over 12 months of bezafibrate therapy. Pruritus was substantially alleviated in the 3 patients after initiation of bezafibrate. Cholestasis was alleviated in 2 of them. Serum high-density lipoprotein cholesterol and low-density lipoprotein cholesterol increased 1.6- to 2.0-fold and 1.1 - to 1.2-fold, respectively; but the values remained low and normal, respectively. Serum lipoprotein X, which was at normal levels before treatment, was elevated to levels above the upper limit of the reference range. High serum triglyceride levels decreased by 15% to 30%, to normal levels, after treatment initiation. The activities of lipoprotein lipase and hepatic triglyceride lipase were increased, but those of high-density lipoprotein regulators remained unchanged. Liver expression Of multidrug resistance protein-3, which regulates lipoprotein X synthesis, was enhanced by bezafibrate therapy. Bezafibrate treatment favorably affected pruritus, dyslipidemia, and cholestasis in PFIC-1. (C) 2009 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.metabol.2008.08.005

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  • Children’s toxicology from bench to bed - Liver Injury (3): Oxidative stress and anti-oxidant systems in liver of patients with wilson disease

    H.Nagasaka, M.Takayanagi, H.Tsukahara

    J Toxicol Sci   34 ( 2 )   SP229 - SP236   2009年

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  • 知っておきたい泌尿器科の知識(その1)- 2. 周産期における腎機能の発達

    塚原 宏一, 巨田 尚子, 徳力 周子, 森 夕起子

    小児外科   41 ( 2 )   98 - 103   2009年

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  • 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. 小児の事故 - 誤飲・誤嚥・頭部外傷の迅速・適確な対処とは

    田村 知史, 塚原 宏一

    内科   103 ( 2 )   362 - 366   2009年

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  • 先天代謝異常症における一酸化窒素代謝系の病態学的意義の探索: 新規の予防・治療法の開発に向けて

    塚原 宏一, 巨田 尚子, 徳力 周子

    福井大学重点研究成果集2009:明日への挑戦   64 - 65   2009年

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  • 小児科領域における一酸化炭素ヘモグロビン・メトヘモグロビンの臨床生化学的意義

    塚原 宏一

    平成20年度腎不全病態研究助成成果報告書   2009年

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  • VURに対する抗生剤予防内服: pros and cons - 小児腎臓病専門医の立場から

    塚原 宏一

    第17回日本逆流性腎症フォーラム記録集   2009年

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  • 小児腎疾患の診断・治療戦略. III. 腎疾患に用いられる治療法 – 12. 尿路感染症予防を目的とする抗菌薬投与

    塚原 宏一

    小児内科   41 ( 2 )   294 - 296   2009年

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  • 小児腎疾患の診断・治療戦略. III. 腎疾患に用いられる治療法 – 12. 尿路感染症予防を目的とする抗菌薬投与

    塚原 宏一

    小児内科   41 ( 2 )   294 - 296   2009年

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  • 知っておきたい泌尿器科の知識(その1)- 2. 周産期における腎機能の発達

    塚原 宏一, 巨田 尚子, 徳力 周子, 森 夕起子

    小児外科   41 ( 2 )   98 - 103   2009年

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  • 小児科領域における一酸化炭素ヘモグロビン・メトヘモグロビンの臨床生化学的意義

    塚原 宏一

    平成20年度腎不全病態研究助成成果報告書   2009年

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  • 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20年度科学研究費補助金実績報告書(基盤研究C)   2009年

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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年

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  • 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年

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  • 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年

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  • 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年

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  • 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. 小児の事故 - 誤飲・誤嚥・頭部外傷の迅速・適確な対処とは

    田村 知史, 塚原 宏一

    内科   103 ( 2 )   362 - 366   2009年

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  • 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20年度科学研究費補助金実績報告書(基盤研究C)   2009年

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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年

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  • 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年

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  • 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年

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  • 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年

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  • 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年

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  • 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年

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  • 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年

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  • 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年

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  • 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年

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  • 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年

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  • Children's toxicology from bench to bed - Liver Injury (3): Oxidative stress and anti-oxidant systems in liver of patients with Wilson disease

    Hironori Nagasaka, Masaki Takayanagi, Hirokazu Tsukahara

    Journal of Toxicological Sciences   34 ( 2 )   SP229 - SP236   2009年

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    記述言語:英語  

    The role of oxidative stress in the pathogenesis of liver disease in Wilson disease (WD), a genetic disorder characterized by excess hepatic deposition of copper, which generates free radicals, remains unclear. This study investigates oxidative stress on the liver and hepatic anti-oxidant responses in WD using liver specimens from affected patients showing mild liver damage (group I, n = 3), moderate or greater liver damage (group II, n = 5) and fulminant hepatic failure (group III, n = 5), and from asymptomatic carriers (n = 2). Decreased ratios of reduced glutathione (GSH) to oxidized glutathione (GSSG) and increased thiobarbituric acid reactive substance (TBARS), a lipid peroxidation product, were found in every affected patient, especially in groups II and III patients. Activities and protein expressions of Mn-dependent superoxide dismutase (Mn-SOD), CuZn-SOD, and catalase were decreased in all patients, especially in group III patients. Glutathione peroxidase activity was decreased only in group III patients. Asymptomatic carriers without any clinical manifestations showed normal TBARS level and GSH/GSSG ratio with increases in both GSH and GSSG levels. Their CuZn-SOD, Mn-SOD and catalase activities were increased. These results suggest that excessive copper-derived oxidants contribute to development and progression of liver disease in WD.

    DOI: 10.2131/jts.34.SP229

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  • 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年

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  • 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年

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  • 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年

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  • 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年6月

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    記述言語:英語   出版者・発行元: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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  • 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年6月

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    記述言語:英語   出版者・発行元: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年3月

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    記述言語:英語   出版者・発行元: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 &lt; 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 &lt; 0.001; at 3 - 4 months of age, 159 +/- 29 vs. 71 similar to 16 and 73 +/- 15 mg/dl, P &lt; 0.001; at 12 months of age, 156 +/- 29 vs. 75 +/- 18 and 76 +/- 17 mg/dl, P &lt; 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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  • 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年3月

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    記述言語:英語   出版者・発行元: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 &lt; 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 &lt; 0.001; at 3 - 4 months of age, 159 +/- 29 vs. 71 similar to 16 and 73 +/- 15 mg/dl, P &lt; 0.001; at 12 months of age, 156 +/- 29 vs. 75 +/- 18 and 76 +/- 17 mg/dl, P &lt; 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年2月

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    記述言語:英語   出版者・発行元: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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  • 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年2月

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    記述言語:英語   出版者・発行元: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年1月

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    記述言語:英語   出版者・発行元: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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  • 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年1月

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    記述言語:英語   出版者・発行元: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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  • 先天性腎尿路異常症児における骨代謝・骨発育の臨床検査医学的評価

    塚原 宏一

    平成19年度腎不全病態研究助成成果報告書   2008年

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  • 新生児の循環の適応生理: 新生児の心臓血管ホルモンの適応生理

    塚原 宏一

    Neonatal Care   21 ( 5 )   437 - 444   2008年

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  • 新生児骨代謝の評価: 特に子宮収縮抑制剤の作用について

    徳力 周子, 塚原 宏一, 古畑 律代, 巨田 尚子, 田村 知史, 畑 郁江, 西島 浩二, 宿南 憲一, 小辻 文和, 眞弓 光文

    小児科臨床   61 ( 5 )   1003 - 1009   2008年

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  • 座談会: AKIの早期診断・早期治療へ向けて

    野入 英世, 伊西 洋二, 塚原 宏一, 菅谷 健

    内科   102 ( 1 )   115 - 124   2008年

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  • 動脈管早期閉鎖により新生児遷延性肺高血圧症をきたした1例

    巨田 尚子, 田村 知史, 徳力 周子, 小倉 一将, 畑 郁江, 塚原 宏一, 鈴木 千代, 西島 浩二, 折坂 誠, 小辻 文和, 眞弓 光文

    小児科臨床   61 ( 8 )   1685 - 1689   2008年

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  • 動脈管早期閉鎖により新生児遷延性肺高血圧症をきたした1例

    巨田 尚子, 田村 知史, 徳力 周子, 小倉 一将, 畑 郁江, 塚原 宏一, 鈴木 千代, 西島 浩二, 折坂 誠, 小辻 文和, 眞弓 光文

    小児科臨床   61 ( 8 )   1685 - 1689   2008年

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  • 超早産児での晩期循環不全発症予防におけるナトリウム補充の重要性

    徳力 周子, 塚原 宏一, 古畑 律代, 巨田 尚子, 田村 知史, 鈴木 孝二, 畑 郁江, 眞弓 光文

    小児科臨床   61 ( 8 )   1679 - 1684   2008年

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  • 要注意 - この感染症にこの合併症. 水痘感染後の脳梗塞

    奥野 貴士, 川谷 正男, 中井 昭夫, 畑 郁江, 塚原 宏一, 谷澤 昭彦, 眞弓 光文

    小児内科   40 ( 3 )   532 - 534   2008年

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  • 胎児・胎盤機能を維持する分子機構の解明と周産期疾患の治療介入についての統合的研究

    眞弓 光文, 塚原 宏一

    平成17~19年度科学研究費補助金(基盤研究B)研究成果報告書   2008年

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  • 胎児期・乳幼児期・学童期・思春期においてアルギニン代謝が循環制御に果たす役割についての分子医学的研究: 統合創薬の開拓に向けて

    塚原 宏一, 巨田 尚子

    福井大学重点研究成果集   72 - 73   2008年

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  • 先天性腎尿路異常症児における骨代謝・骨発育の臨床検査医学的評価

    塚原 宏一

    平成19年度腎不全病態研究助成成果報告書   2008年

     詳細を見る

  • 新生児の循環の適応生理: 新生児の心臓血管ホルモンの適応生理

    塚原 宏一

    Neonatal Care   21 ( 5 )   437 - 444   2008年

     詳細を見る

  • 新生児骨代謝の評価: 特に子宮収縮抑制剤の作用について

    徳力 周子, 塚原 宏一, 古畑 律代, 巨田 尚子, 田村 知史, 畑 郁江, 西島 浩二, 宿南 憲一, 小辻 文和, 眞弓 光文

    小児科臨床   61 ( 5 )   1003 - 1009   2008年

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  • Clinical significance of the balance between the L-arginine/NOS/NO pathway and the PRMT/ADMA/DDAH pathway

    H.Tsukahara, N.Oota, S.Tokuriki, S.Tamura, M.Toyooka, K.Nishijima, M.Orisaka, F.Kotsuji, N.Ohta, H.Kawakami, K.Sekine, H.Nagasaka, M.Mayumi

    Journal of Developmental Nephrology(発達腎研究会誌)   16 ( 1 )   21 - 28   2008年

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  • 座談会: AKIの早期診断・早期治療へ向けて

    野入 英世, 伊西 洋二, 塚原 宏一, 菅谷 健

    内科   102 ( 1 )   115 - 124   2008年

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  • BOOK REVIEW: 新生児医療 - 治療方針選択に役立つ論文245(京都大学医学部附属病院NICU 河井昌彦編著). 新生児医療を担う若手医師の実力向上を後押しする1冊

    塚原 宏一

    日本医事新報   4404   35   2008年

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  • 薬に関する素朴な疑問. 各論 - 泌尿・生殖器疾患: 尿路感染症の予防には何を用いますか、ST合剤の方がセファクロルより有効ですか

    塚原 宏一

    小児内科   40 ( 2 )   430 - 431   2008年

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  • 薬に関する素朴な疑問. 各論 - 泌尿・生殖器疾患: 尿路感染症に対して抗菌薬はどのくらいの期間使用すればよいですか

    塚原 宏一

    小児内科   40 ( 2 )   428 - 429   2008年

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  • 前置癒着胎盤及び広範な前壁付着を伴う前置胎盤に対する新たな帝王切開法:子宮底部横切開法の安全性と有用性

    西島 浩二, 宿南 憲一, 折坂 誠, 田嶋 公久, 塚原 宏一, 河合 泰一, 吉田 好雄, 小辻 文和

    日本産婦人科・新生児血液学会誌   17 ( 2 )   39 - 42   2008年

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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年

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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年

  • 薬に関する素朴な疑問. 各論 - 泌尿・生殖器疾患: 尿路感染症に対して抗菌薬はどのくらいの期間使用すればよいですか

    塚原 宏一

    小児内科   40 ( 2 )   428 - 429   2008年

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  • 超早産児での晩期循環不全発症予防におけるナトリウム補充の重要性

    徳力 周子, 塚原 宏一, 古畑 律代, 巨田 尚子, 田村 知史, 鈴木 孝二, 畑 郁江, 眞弓 光文

    小児科臨床   61 ( 8 )   1679 - 1684   2008年

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  • BOOK REVIEW: 新生児医療 - 治療方針選択に役立つ論文245(京都大学医学部附属病院NICU 河井昌彦編著). 新生児医療を担う若手医師の実力向上を後押しする1冊

    塚原 宏一

    日本医事新報   4404   35   2008年

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  • 小児疾患診療のための病態生理1 - IV. 腎・泌尿器疾患. 11. 尿路感染症

    塚原 宏一

    小児内科   40   867 - 873   2008年

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  • 早期新生児のDIC診断基準: 多施設共同研究による京都大学案の検討

    河井 昌彦, 丹羽 房子, 松倉 崇, 水本 洋, 金岡 裕夫, 松原 康策, 塚原 宏一, 前田 真治, 黒須 英雄, 吉岡 孝和, 武藤 庫参, 中畑 龍俊

    日本周産期新生児医学会雑誌   44 ( 4 )   1180 - 1185   2008年

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  • Clinical significance of the balance between the L-arginine/NOS/NO pathway and the PRMT/ADMA/DDAH pathway

    H.Tsukahara, N.Oota, S.Tokuriki, S.Tamura, M.Toyooka, K.Nishijima, M.Orisaka, F.Kotsuji, N.Ohta, H.Kawakami, K.Sekine, H.Nagasaka, M.Mayumi

    Journal of Developmental Nephrology   16 ( 1 )   21 - 28   2008年

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  • 小児疾患診療のための病態生理1 - IV. 腎・泌尿器疾患. 11. 尿路感染症

    塚原 宏一

    小児内科   40   867 - 873   2008年

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  • 早期新生児のDIC診断基準: 多施設共同研究による京都大学案の検討

    河井 昌彦, 丹羽 房子, 松倉 崇, 水本 洋, 金岡 裕夫, 松原 康策, 塚原 宏一, 前田 真治, 黒須 英雄, 吉岡 孝和, 武藤 庫参, 中畑 龍俊

    日本周産期新生児医学会雑誌   44 ( 4 )   1180 - 1185   2008年

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  • 超低出生体重児の消化管成熟に向けた治療戦略:肺サーファクタントを用いた動物実験

    西島 浩二, 宿南 憲一, 高橋 仁, 塚原 宏一, 小辻 文和

    日本周産期・新生児医学会雑誌   2008年

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  • 薬に関する素朴な疑問. 各論 - 泌尿・生殖器疾患: 尿路感染症の予防には何を用いますか、ST合剤の方がセファクロルより有効ですか

    塚原 宏一

    小児内科   40 ( 2 )   430 - 431   2008年

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  • Leukotriene D-4 enhances the function of endothelin-1-primed fibroblasts

    Shuko Tokuriki, Yusei Ohshima, Akiko Yamada, Naoko Ohta, Hirokazu Tsukahara, Mitsufumi Mayumi

    CLINICAL IMMUNOLOGY   125 ( 1 )   88 - 94   2007年10月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Airway inflammation is accompanied by structural changes, termed remodeling, that lead to lung dysfunction over the tong term. Although both endothelin-1 (ET-1) and cysteinyl leukotrienes (CysLTs) appear to be involved in airway remodeling in several lung diseases, how these molecules interact remains largely unknown. In this study, we examined the effects of leukotriene (LT) D-4 on the function of ET-1-primed fibroblasts. ET-1 at 10(-7) M up-regulated the expression of the CysLT receptors at both the mRNA and protein levels in human lung fibroblasts. LTD4 enhanced matrix metalloproteinase-2 and pro-collagen production, and a-smooth muscle actin expression of ET-1-primed fibroblasts, but had little or no effect on unprimed fibroblasts. The CysLT1 receptor antagonist montelukast completely abrogated the effects of LTD4. Our data suggested that LTD4 may act as a precipitating factor during ET-1-mediated airway remodeling and that CysLT1 receptor antagonists may have a rote in preventing aberrant extracellutar matrix degradation. (c) 2007 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.clim.2007.05.018

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  • PTを重視した早期新生児期のDIC診断基準 多施設での検討に基づくPT基準値の変更

    河井 昌彦, 松倉 崇, 水本 洋, 丹羽 房子, 金岡 裕夫, 塚原 宏一, 武藤 庫参, 中畑 龍俊

    日本未熟児新生児学会雑誌   19 ( 3 )   631 - 631   2007年10月

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    記述言語:日本語   出版者・発行元:(一社)日本新生児成育医学会  

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  • Depletion of high-density lipoprotein and appearance of triglyceride-rich low-density lipoprotein in a Japanese patient with FIC1 deficiency manifesting benign recurrent intrahepatic cholestasis

    Hironori Nagasaka, Hitoshi Chiba, Shu-Ping Hui, Hajime Takikawa, Takashi Miida, Masaki Takayanagi, Tohru Yorifuji, Makoto Hasegawa, Akemi Ota, Ken-ichi Hirano, Hideaki Kikuchi, Hirokazu Tsukahara, Kunihiko Kobayashi

    JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION   45 ( 1 )   96 - 105   2007年7月

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    記述言語:英語   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Objective: Lipoprotein metabolism in FIC I deficiency due to ATP8B1 mutations has never been studied sufficiently. This study was performed to investigate the detailed lipoprotein metabolism in benign recurrent intrahepatic cholestasis (BRIC) caused by FIC1 deficiency.
    Patients and Methods: Lipoprotein profile and major lipoprotein regulators such as lecithin: cholesterol acyltransferase (LCAT), hepatic triglyceride lipase (HTGL), lipoprotein lipase, and cholesteryl ester transfer protein in a Japanese patient with BRIC were serially examined during a bout of cholestasis. Liver expression of farnesoid X receptor (FXR), which suppresses high-density lipoprotein (HDL) generation., was also examined.
    Results: Hypercholesterolemia and lipoprotein X accumulation were never observed throughout this study. When the cholestasis was severe, triglyceride-rich low-density lipoprotem (LDL) accounted for most of the plasma lipoproteins whereas HDL was hardly detectable. Concurrently, activities of all regulators were decreased, together with decreases of the serum parameter for liver protein synthesis. In particular, suppressions of LCAT and HTGL activities were severe and greatly contributed to the appearance of triglyceride-rich LDL. As the cholestasis improved, this LDL gradually transformed into normal LDL with the recoveries of LCAT and HTGL activities. The activities of all regulators for the last I to 2 months were normal but HDL remained depleted. His liver showed low FXR expression compared with control livers.
    Conclusions: The present study showed an appearance of triglyceride-rich LDL due to suppressions of LCAT and HTGL activities and a depletion of HDL that is not able to be explained by lipoprotein regulators or FXR in our patient.

    DOI: 10.1097/MPG.0b013e3180331df9

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  • 小児の腎機能検査

    塚原 宏一

    臨床化学   36   113 - 113   2007年6月

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  • プロトロンビン時間を重視した早期新生児期のDIC診断基準 多施設共同での検討結果(第1報)

    河井 昌彦, 水本 洋, 丹羽 房子, 金岡 裕夫, 松原 康策, 塚原 宏一, 武藤 庫参, 中畑 龍俊

    日本産婦人科・新生児血液学会誌   17 ( 1 )   S - 35   2007年6月

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    記述言語:日本語   出版者・発行元:日本産婦人科・新生児血液学会  

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  • 新生児医療の処置に関する合併症の検討

    水本 洋, 丹羽 房子, 河井 昌彦, 中畑 龍俊, 奥村 光祥, 加藤 文英, 金岡 裕夫, 黒須 英雄, 塚原 宏一, 橋本 和廣, 前田 真治, 山川 勝, 吉岡 孝和

    日本小児科学会雑誌   111 ( 2 )   426 - 426   2007年2月

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    記述言語:日本語   出版者・発行元:(公社)日本小児科学会  

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  • Lowest effective dose of dexamethasone in the respiratory care of very preterm infants

    Hirokazu Tsukahara, Mitsufumi Mayumi

    EARLY HUMAN DEVELOPMENT   83 ( 1 )   3 - 3   2007年1月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.earlhumdev.2006.04.001

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  • 糖尿病血管系合併症における分子機構の解明と治療戦略への応用(研究課題番号 17591074)

    塚原 宏一

    平成17~18年度科学研究費補助金(基盤研究C)研究成果報告書   2007年

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  • 平成18年度厚生労働科学研究費補助金(子ども家庭総合研究事業)総括研究報告書: 小児難治性腎尿路疾患の早期発見、診断管理・治療に関する研究(主任研究者 五十嵐隆)

    五十嵐 隆, 伊藤 雄平, 松山 健, 塚原 宏一, 中井 秀郎, 飯島 一誠, 塚口 裕康, 関根 孝司, 吉川 徳茂, 本田 雅敬, 山内 邦昭, 二宮 誠, 宮田 純一, 北村 明子, 中西 浩一, 佐古 まゆみ, 服部 新三郎, 和田 尚弘

    平成18年度厚生労働科学研究費補助金(子ども家庭総合研究事業)総括・分担研究報告書   1 - 23   2007年

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  • 平成18年度厚生労働科学研究費補助金(子ども家庭総合研究事業)分担研究報告書: 小児難治性腎尿路疾患の早期発見、診断管理・治療に関する研究(主任研究者 五十嵐隆). 尿路感染症の診断、治療、管理システムの構築に関する研究

    塚原 宏一

    平成18年度厚生労働科学研究費補助金(子ども家庭総合研究事業)総括・分担研究報告書   58 - 62   2007年

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  • 平成16年度厚生労働科学研究費補助金(子ども家庭総合研究事業)総合研究報告書: 小児難治性腎尿路疾患の早期発見、診断管理・治療に関する研究(主任研究者 五十嵐隆)

    五十嵐 隆, 松山 健, 伊藤 雄平, 平岡 政弘, 塚原 宏一, 中井 秀郎, 飯島 一誠, 塚口 裕康, 関根 孝司, 吉川 徳茂, 本田 雅敬

    平成16年度~18年度厚生労働科学研究費補助金(子ども家庭総合研究事業)総合研究報告書   1-8   2007年

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  • 平成17年度厚生労働科学研究費補助金(子ども家庭総合研究事業)総合研究報告書: 小児難治性腎尿路疾患の早期発見、診断管理・治療に関する研究(主任研究者 五十嵐隆)

    五十嵐 隆, 松山 健, 伊藤 雄平, 塚原 宏一, 中井 秀郎, 飯島 一誠, 塚口 裕康, 関根 孝司, 吉川 徳茂, 本田 雅敬, 服部 新三郎, 幡谷 浩志, 和田 尚弘

    平成16年度~18年度厚生労働科学研究費補助金(子ども家庭総合研究事業)総合研究報告書   9 - 24   2007年

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  • 平成18年度厚生労働科学研究費補助金(子ども家庭総合研究事業)総合研究報告書: 小児難治性腎尿路疾患の早期発見、診断管理・治療に関する研究(主任研究者 五十嵐隆)

    五十嵐 隆, 伊藤 雄平, 松山 健, 塚原 宏一, 中井 秀郎, 飯島 一誠, 塚口裕康, 関根 孝司, 吉川 徳茂, 本田 雅敬, 服部 新三郎, 幡谷 浩志, 和田 尚弘

    平成16年度~18年度厚生労働科学研究費補助金(子ども家庭総合研究事業)総合研究報告書   25 - 48   2007年

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  • 新生児期の栄養管理と長期予後: 早産児の栄養管理と骨発達

    塚原 宏一

    第7回新生児栄養フォーラム発表論文集   58 - 65   2007年

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  • 慢性腎臓病 - CKDキャンペーンをめぐる話題 - 国内外のCKDに対するエビデンス: 小児CKD

    塚原 宏一

    内科   100 ( 1 )   79 - 83   2007年

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  • エリスロポイエチン高値の生体応答学的意義について

    塚原 宏一, 小倉 一将, 古畑 律代, 田村 知史, 眞弓 光文, 西島 浩二, 宿南憲一, 小辻 文和, 上野正樹

    発達腎研究会誌   15 ( 1 )   25 - 33   2007年

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  • 酸化ストレスとレドックス制御

    塚原 宏一

    総合臨床   56 ( 10 )   2915 - 2918   2007年

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  • 腎・泌尿器疾患診療マニュアル - 小児から成人まで: Kの異常(小児)

    塚原 宏一

    日本医師会雑誌   136   S102-S103   2007年

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  • 腎尿路異常症患者における酸化ストレス環境の評価:当院の年齢別基準値に基づいて

    塚原 宏一, 平岡 政弘, 森 夕起子, 巨田 尚子, 徳力 周子, 川谷 正男, 長坂 博範, 川上 寿子, 関根 恭一, 眞弓 光文

    小児腎臓病学会雑誌   20 ( 2 )   131 - 135   2007年

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  • 周生期の循環制御: 特に母乳中の血管作動因子の分析についての研究

    塚原 宏一

    平成16年財団法人森永奉仕会太田敬三記念賞: 研究実績報告書   2007年

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  • Procedures for prevention of perinatal group B streptococcal diseases: A multicenter questionnaire survey of hospitals in the Kyoto Neonatal Disease Study Group, Japan

    Kousaku Matsubara, Masahiko Kawai, Tatsutoshi Nakahata, Fumihide Kato, Hirokazu Tsukahara, Masaru Yamakawa, Kazuhiro Hashimoto, Seiichi Shimada, Shinji Maeda, Mitsuyoshi Okumura, Hiroo Kanaoka

    Journal of Infection and Chemotherapy   13 ( 1 )   59 - 62   2007年

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:Springer Japan  

    To explore clinical protocols for the prevention of early-onset group B Streptococcus (EOGBS) disease of the newborn in Japan, we conducted a multicenter questionnaire survey. Of 32 regional centers participating in the Kyoto Neonatal Study Group, 28 provided usable data concerning prevention practices undertaken between 2000 and 2004. Twenty-three (82%) of the 28 hospitals implemented bacteriological screening to identify maternal GBS carriage, and all 23 hospitals administered intrapartum antibiotics to all screening-positive pregnant women. There were no institutes that used risk-based strategies. In the 23 hospitals, bacteriological screening was conducted mostly by lower vaginal swab alone (n = 18). Eighteen hospitals performed screening once during pregnancy, either before 34 weeks' gestation (n = 6) or between 35 and 37 weeks' gestation (n = 12). Oral antepartum antibiotics, when carriage was identified, were administered at 12 (52%) hospitals. Twenty institutes used penicillins for intrapartum prophylaxis. However, the loading dose for chemoprophylaxis ranged from 0.5 to 2g, and the interval between repeat administrations ranged from 4 to 12h. Although the results indicated that more than 80% of the hospitals surveyed had introduced some screening-based prevention practices, the timing of the bacteriological screening during the pregnancy, the number of screenings, and the screening sites, as well as the antibiotics used, and their dosage, varied widely. Because of these highly variable methods, the efficacy of the implementation of preventive practices could not be determined. This study is the first to have described preventive practices for EOGBS disease in Japan in the era of Centers for Disease Control and Prevention guidelines. In light of the above results, a larger study under a unifying protocol would be warranted. © 2007 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.

    DOI: 10.1007/s10156-006-0487-2

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  • Biomarkers for oxidative stress: Clinical application in pediatric medicine

    Hirokazu Tsukahara

    CURRENT MEDICINAL CHEMISTRY   14 ( 3 )   339 - 351   2007年

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:BENTHAM SCIENCE PUBL LTD  

    Loads of reactive oxygen species (ROS), including superoxide anion and nitric oxide, that overburden antioxidant systems induce oxidative stress in the body. Major cellular targets of ROS are membrane lipids, proteins, nucleic acids, and carbohydrates. Circumstantial evidence suggests that ROS play a crucial role in the initiation and progression of various diseases in children and adolescents. The involvement of ROS and oxidative stress in pediatric diseases is an important concern, but oxidative stress status in young subjects and appropriate methods for its measurement remain to be defined. Recently, specific biomarkers for oxidative damage and antioxidant defense have been introduced into the field of pediatric medicine. This review is intended to provide an overview of clinical applications of oxidative stress biomarkers in the field of pediatric medicine. First, this review presents the biochemistry and pathophysiology of ROS and antioxidant defense systems. Second, it presents a list of clinically applicable biomarkers, along with pediatric diseases in which enhanced oxidative stress might be involved. The discussion emphasizes that several reliable biomarkers are easily measurable using enzyme-linked immunosorbent assay. Third, this review presents age-related reference normal ranges of oxidative stress biomarkers, including urinary acrolein-lysine, 8-hydroxy-2&apos;-deoxyguanosine, nitrite/nitrate, and pentosidine, and the changes of the parameters in several clinical conditions, including atopic dermatitis and diabetes mellitus. New and interesting data on oxidative stress and antioxidant defenses in neonatal biology are also presented. Fourth, this review discusses the ever-accumulating body of data linking oxidative stress to disturbances of the nitric oxide system and vascular endothelial activation/dysfunction. Finally, this review describes the reported clinical trials that have evaluated the efficacy of antioxidants for oxidative-stress related diseases. Suggestions are advanced for the direction of future trials using antioxidant therapies. Repeated measurement of appropriate parameters will enable us to discern the pathophysiological patterns of pediatric diseases and guide our therapies appropriately.

    DOI: 10.2174/092986707779941177

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  • Evaluation of a urinary multi-parameter biomarker set for oxidative stress in children, adolescents and young adults

    Satoshi Tamura, Hirokazu Tsukahara, Masaki Ueno, Masayuki Maeda, Hisako Kawakami, Kyouichi Sekine, Mitsufumi Mayumi

    FREE RADICAL RESEARCH   40 ( 11 )   1198 - 1205   2006年11月

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    記述言語:英語   出版者・発行元:TAYLOR & FRANCIS LTD  

    The involvement of reactive oxygen species (ROS) and oxidative stress in pediatric diseases is an important concern, but oxidative stress status in healthy young subjects and appropriate methods for its measurement remain unclear. This study evaluated a comprehensive set of urinary biomarkers for oxidative stress in healthy children, adolescents and young adults. Results show that urinary excretion of acrolein-lysine, 8-hydroxy-2&apos;-deoxyguanosine (8-OHdG), nitrite/nitrate and pentosidine were highest in the youngest subjects and decreased to constant levels by early adolescence. Urinary acrolein lysine, 8-OHdG, nitrite/nitrate and pentosidine showed significant inverse correlations with age, but pyrraline did not change significantly with age. No significant differences in biomarkers were apparent between males and females. Younger subjects grow rapidly and sustain immune activation, and are probably exposed to high concentrations of ROS and nitric oxide. Consequently, they are more vulnerable to oxidation of lipids, proteins, DNA and carbohydrates. Normal reported values in this study are a basis for future studies of disease mechanisms involving oxidative stress and for future trials using antioxidant therapies for oxidative stress-related diseases in the pediatric field.

    DOI: 10.1080/10715760600895191

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  • Evaluation of a urinary multi-parameter biomarker set for oxidative stress in children, adolescents and young adults

    Satoshi Tamura, Hirokazu Tsukahara, Masaki Ueno, Masayuki Maeda, Hisako Kawakami, Kyouichi Sekine, Mitsufumi Mayumi

    FREE RADICAL RESEARCH   40 ( 11 )   1198 - 1205   2006年11月

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    記述言語:英語   出版者・発行元:TAYLOR & FRANCIS LTD  

    The involvement of reactive oxygen species (ROS) and oxidative stress in pediatric diseases is an important concern, but oxidative stress status in healthy young subjects and appropriate methods for its measurement remain unclear. This study evaluated a comprehensive set of urinary biomarkers for oxidative stress in healthy children, adolescents and young adults. Results show that urinary excretion of acrolein-lysine, 8-hydroxy-2&apos;-deoxyguanosine (8-OHdG), nitrite/nitrate and pentosidine were highest in the youngest subjects and decreased to constant levels by early adolescence. Urinary acrolein lysine, 8-OHdG, nitrite/nitrate and pentosidine showed significant inverse correlations with age, but pyrraline did not change significantly with age. No significant differences in biomarkers were apparent between males and females. Younger subjects grow rapidly and sustain immune activation, and are probably exposed to high concentrations of ROS and nitric oxide. Consequently, they are more vulnerable to oxidation of lipids, proteins, DNA and carbohydrates. Normal reported values in this study are a basis for future studies of disease mechanisms involving oxidative stress and for future trials using antioxidant therapies for oxidative stress-related diseases in the pediatric field.

    DOI: 10.1080/10715760600895191

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  • Reversible splenial lesion with restricted diffusion in a wide spectrum of diseases and conditions - Report of eight additional cases and literature review

    M. Maeda, H. Tsukahara, H. Terada, S. Nakaji, H. Nakamura, H. Oba, O. Igarashi, K. Arasaki, T. Machida, K. Takeda, J. I. Takanashi

    JOURNAL OF NEURORADIOLOGY   33 ( 4 )   229 - 236   2006年10月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:MASSON EDITEUR  

    Objective: Reversible lesion in the central area of the splenium of the corpus callosum (SCC) is a unique phenomenon occurring particularly in patients with encephalitis or encephalopathy and in patients receiving antiepileptic drugs (AED). We report MR imaging findings, clinical courses, and outcomes in eight patients with various diseases and conditions.
    Materials and methods: Eight patients with a reversible SCC lesion with transiently restricted diffusion were reviewed retrospectively. Diseases and conditions that were associated with a reversible lesion included epilepsy receiving AED (n=1), seizure from eclampsia receiving AED (n=1), mild infectious encephalitis (n=2), hypernatremia resulting in osmotic myelinolysis (n=1), and neoplasm (n=3) such as acute lymphocytic leukemia, spinal meningeal melanocytoma, and esophageal cancer. We evaluated MR imaging findings and clinical findings.
    Results: Seven patients had isolated SCC lesions; one patient with osmotic myelinolysis showed additional parenchymal lesions. The reversible SCC lesion shape was oval (n=6) or extended (n=2). The mean apparent diffusion coefficient value of the splenial lesion was 0.40 +/- 0.16x10(-3)mm(2)/s, ranging from 0.22 to 0.64x10(-3)mm(2)/s. In a patient with osmotic myelinolysis, additional white matter lesions, shown as restricted diffusion, were revealed as not reversible on follow-up MR imaging. Neurological courses and outcomes were good in seven patients with isolated SCC lesions, but poor in one with osmotic myelinolysis.
    Conclusion: Reversible SCC lesion with restricted diffusion is apparent in a wide spectrum of diseases and conditions. Neurological courses and outcomes are good, particularly in patients with isolated SCC lesions. Knowledge of MR imaging findings and the associated spectrum of diseases and conditions might prevent unnecessary invasive examinations and treatments.

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  • Relationship between oxidative stress and antioxidant systems in the liver of patients with Wilson disease: Hepatic manifestation in Wilson disease as a consequence of augmented oxidative stress

    Hironori Nagasaka, Ikuo Inoue, Ayano Inui, Haruki Komatsu, Tsuyoshi Sogo, Kei Murayama, Tomoko Murakami, Tohru Yorifuji, Kotaro Asayama, Shigeo Katayama, Shinji Uemoto, Kunihiko Kobayashi, Masaki Takayanagi, Tomoo Fujisawa, Hirokazu Tsukahara

    PEDIATRIC RESEARCH   60 ( 4 )   472 - 477   2006年10月

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    記述言語:英語   出版者・発行元:INT PEDIATRIC RESEARCH FOUNDATION, INC  

    The role of oxidative stress in the pathogenesis of liver disease in Wilson disease (WD), a genetic disorder characterized by excess hepatic deposition of copper that generates free radicals, remains unclear. This study investigates oxidative stress on the liver and hepatic antioxidant responses in WD using liver specimens from affected patients showing mild liver damage (group 1, n = 3), moderate or greater liver damage (group 11, n = 5), and fulminant hepatic failure (group 111, n = 5) and from asymptomatic carriers (n = 2). Decreased ratios of reduced glutathione (GSH) to oxidized glutathione (GSSG) and increased thiobarbituric acid reactive substance (TBARS), a lipid peroxidation product, were found in every affected patient, especially in group 11 and III patients. Activities and protein expressions of Mn-dependent superoxide dismutase (Mn-SOD), CuZn-dependent superoxide dismutase (CuZn-SOD), and catalase were decreased in all patients, especially in group III patients. Glutathione peroxidase (GPx) activity was decreased only in group III patients. Asymptomatic carriers without any clinical manifestations showed normal TBARS level and GSH/GSSG ratio with increases in both GSH and GSSG levels. Their CuZn-SOD, MnSOD, and catalase activities were increased. These results suggest that excessive copper-derived oxidants contribute to development and progression of liver disease in WD.

    DOI: 10.1203/01.pdr.0000238341.12229.d3

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  • Relationship between oxidative stress and antioxidant systems in the liver of patients with Wilson disease: Hepatic manifestation in Wilson disease as a consequence of augmented oxidative stress

    Hironori Nagasaka, Ikuo Inoue, Ayano Inui, Haruki Komatsu, Tsuyoshi Sogo, Kei Murayama, Tomoko Murakami, Tohru Yorifuji, Kotaro Asayama, Shigeo Katayama, Shinji Uemoto, Kunihiko Kobayashi, Masaki Takayanagi, Tomoo Fujisawa, Hirokazu Tsukahara

    PEDIATRIC RESEARCH   60 ( 4 )   472 - 477   2006年10月

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    記述言語:英語   出版者・発行元:INT PEDIATRIC RESEARCH FOUNDATION, INC  

    The role of oxidative stress in the pathogenesis of liver disease in Wilson disease (WD), a genetic disorder characterized by excess hepatic deposition of copper that generates free radicals, remains unclear. This study investigates oxidative stress on the liver and hepatic antioxidant responses in WD using liver specimens from affected patients showing mild liver damage (group 1, n = 3), moderate or greater liver damage (group 11, n = 5), and fulminant hepatic failure (group 111, n = 5) and from asymptomatic carriers (n = 2). Decreased ratios of reduced glutathione (GSH) to oxidized glutathione (GSSG) and increased thiobarbituric acid reactive substance (TBARS), a lipid peroxidation product, were found in every affected patient, especially in group 11 and III patients. Activities and protein expressions of Mn-dependent superoxide dismutase (Mn-SOD), CuZn-dependent superoxide dismutase (CuZn-SOD), and catalase were decreased in all patients, especially in group III patients. Glutathione peroxidase (GPx) activity was decreased only in group III patients. Asymptomatic carriers without any clinical manifestations showed normal TBARS level and GSH/GSSG ratio with increases in both GSH and GSSG levels. Their CuZn-SOD, MnSOD, and catalase activities were increased. These results suggest that excessive copper-derived oxidants contribute to development and progression of liver disease in WD.

    DOI: 10.1203/01.pdr.0000238341.12229.d3

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  • Reversible splenial lesion with restricted diffusion in a wide spectrum of diseases and conditions - Report of eight additional cases and literature review

    M. Maeda, H. Tsukahara, H. Terada, S. Nakaji, H. Nakamura, H. Oba, O. Igarashi, K. Arasaki, T. Machida, K. Takeda, J. I. Takanashi

    JOURNAL OF NEURORADIOLOGY   33 ( 4 )   229 - 236   2006年10月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:MASSON EDITEUR  

    Objective: Reversible lesion in the central area of the splenium of the corpus callosum (SCC) is a unique phenomenon occurring particularly in patients with encephalitis or encephalopathy and in patients receiving antiepileptic drugs (AED). We report MR imaging findings, clinical courses, and outcomes in eight patients with various diseases and conditions.
    Materials and methods: Eight patients with a reversible SCC lesion with transiently restricted diffusion were reviewed retrospectively. Diseases and conditions that were associated with a reversible lesion included epilepsy receiving AED (n=1), seizure from eclampsia receiving AED (n=1), mild infectious encephalitis (n=2), hypernatremia resulting in osmotic myelinolysis (n=1), and neoplasm (n=3) such as acute lymphocytic leukemia, spinal meningeal melanocytoma, and esophageal cancer. We evaluated MR imaging findings and clinical findings.
    Results: Seven patients had isolated SCC lesions; one patient with osmotic myelinolysis showed additional parenchymal lesions. The reversible SCC lesion shape was oval (n=6) or extended (n=2). The mean apparent diffusion coefficient value of the splenial lesion was 0.40 +/- 0.16x10(-3)mm(2)/s, ranging from 0.22 to 0.64x10(-3)mm(2)/s. In a patient with osmotic myelinolysis, additional white matter lesions, shown as restricted diffusion, were revealed as not reversible on follow-up MR imaging. Neurological courses and outcomes were good in seven patients with isolated SCC lesions, but poor in one with osmotic myelinolysis.
    Conclusion: Reversible SCC lesion with restricted diffusion is apparent in a wide spectrum of diseases and conditions. Neurological courses and outcomes are good, particularly in patients with isolated SCC lesions. Knowledge of MR imaging findings and the associated spectrum of diseases and conditions might prevent unnecessary invasive examinations and treatments.

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  • Micelles of pulmonary surfactant in human amniotic fluid at term

    Koji Nishijima, Ken-Ichi Shukunami, Hirokazu Tsukahara, Makoto Orisaka, Jun&apos;Ichiro Miura, Fumikazu Kotsuji

    PEDIATRIC RESEARCH   60 ( 2 )   196 - 199   2006年8月

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    記述言語:英語   出版者・発行元:INT PEDIATRIC RESEARCH FOUNDATION, INC  

    Studies using in vitro analysis have shown that the interaction between pulmonary surfactant and vernix caseosa could explain the appearance of amniotic fluid turbidity. That phenomenon is interpreted based on the "roll-up" hypothesis. We tested the roll-up hypothesis by examining the presence of micelles of pulmonary surfactant in human amniotic fluid at term. Amniotic fluid samples were collected from each of six healthy pregnant women at term and at 16 wk of gestation. These samples were stained negatively and analyzed using an electron microscope. Ultrastructures present in amniotic fluid were compared with the structure of micelles derived from suspended surfactant TA isolated from bovine lung. Surfactant TA formed spheroidal and rod-shaped micelles 10-70 nm in diameter above the critical micelle concentration. Identical micelle particles were described in human amniotic fluid at term. In addition, surfactant protein B was identified in the micelle fraction of amniotic fluid. However, no micelles were found in human amniotic fluid taken at 16 wk of gestation. Our results support the view that pulmonary surfactant could induce the detachment of vernix caseosa and increase the turbidity of the amniotic fluid.

    DOI: 10.1203/01.pdr.0000228329.90502.3a

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  • Hypocalcemia in mitochondrial trifunctional protein deficiency

    I. Hata, H. Tsukahara, Y. Shigematsu, M. Mayumi

    JOURNAL OF INHERITED METABOLIC DISEASE   29   114 - 114   2006年8月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:SPRINGER  

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  • Urinary creatinine excretion and protein/creatinine ratios vary by body size and gender in children

    Y Mori, M Hiraoka, N Suganuma, H Tsukahara, H Yoshida, M Mayumi

    PEDIATRIC NEPHROLOGY   21 ( 5 )   683 - 687   2006年5月

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    記述言語:英語   出版者・発行元:SPRINGER  

    Urinary protein/creatinine ratio (Up/cr) is a simple measurement for evaluation of proteinuria. However, exact effects of body size and gender on urinary excretion of creatinine and Up/cr remain unknown. We aimed to clarify their effects. Early morning urine samples were collected from 124 children with urinary tract disorders. Urinary hourly excretion of creatinine, Ucr (in milligrams per hour), urinary hourly excretion of protein per body surface area, Up (milligrams per square meter per hour), and Up/cr (milligrams per milligram) were calculated. Effects of gender, age, body height, body weight and body surface area on Ucr and Up/cr were analyzed, respectively, in a multiple linear regression model. Body surface area and gender affected Ucr (r(2)=0.842, P &lt; 0.0001). Ucr adjusted by body surface area increased as body surface area grew with moderate variation. Up/cr showed a close correlation with Up and was affected by body height and gender as well. The regression equation showed that Up/cr values corresponding to the normal upper limit of Up, i.e., 4 mg/m(2)/h, in boys and girls 170 cm tall were approximately one third of those in children 80 cm tall (0.121 vs 0.043 for boys, 0.132 vs 0.047 for girls). The present study indicates that estimation of Up/cr needs to include consideration of children's body height and gender.

    DOI: 10.1007/s00467-005-0001-6

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  • Urinary creatinine excretion and protein/creatinine ratios vary by body size and gender in children

    Y Mori, M Hiraoka, N Suganuma, H Tsukahara, H Yoshida, M Mayumi

    PEDIATRIC NEPHROLOGY   21 ( 5 )   683 - 687   2006年5月

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    記述言語:英語   出版者・発行元:SPRINGER  

    Urinary protein/creatinine ratio (Up/cr) is a simple measurement for evaluation of proteinuria. However, exact effects of body size and gender on urinary excretion of creatinine and Up/cr remain unknown. We aimed to clarify their effects. Early morning urine samples were collected from 124 children with urinary tract disorders. Urinary hourly excretion of creatinine, Ucr (in milligrams per hour), urinary hourly excretion of protein per body surface area, Up (milligrams per square meter per hour), and Up/cr (milligrams per milligram) were calculated. Effects of gender, age, body height, body weight and body surface area on Ucr and Up/cr were analyzed, respectively, in a multiple linear regression model. Body surface area and gender affected Ucr (r(2)=0.842, P &lt; 0.0001). Ucr adjusted by body surface area increased as body surface area grew with moderate variation. Up/cr showed a close correlation with Up and was affected by body height and gender as well. The regression equation showed that Up/cr values corresponding to the normal upper limit of Up, i.e., 4 mg/m(2)/h, in boys and girls 170 cm tall were approximately one third of those in children 80 cm tall (0.121 vs 0.043 for boys, 0.132 vs 0.047 for girls). The present study indicates that estimation of Up/cr needs to include consideration of children's body height and gender.

    DOI: 10.1007/s00467-005-0001-6

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  • Neonatal suppurative parotitis possibly associated with congenital cytomegalovirus infection and maternal methyldopa administration

    Y Todoroki, H Tsukahara, M Kawatani, Y Ohshma, KI Shukunami, F Kotsuji, M Mayumi

    PEDIATRICS INTERNATIONAL   48 ( 2 )   185 - 186   2006年4月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    DOI: 10.1111/j.1442-200X.2006.02188.x

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  • Widening spectrum of a reversible splenial lesion with transiently reduced diffusion

    J Takanashi, AJ Barkovich, T Shiihara, H Tada, M Kawatani, H Tsukahara, M Kikuchi, M Maeda

    AMERICAN JOURNAL OF NEURORADIOLOGY   27 ( 4 )   836 - 838   2006年4月

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    記述言語:英語   出版者・発行元:AMER SOC NEURORADIOLOGY  

    Four patients with encephalitis/encephalopathy and parenchymal lesions accompanying reversible splenial lesions were retrospectively evaluated. In 3 patients, reversible lesions with transiently reduced diffusion were seen in the splenium and symmetrically in the peripheral frontoparietal white matter, clinical signs and symptoms were mild, and recovery was complete. These and previous observations suggest a less severe course and outcome for patients with reversible lesions isolated to the splenium or to the splenium and peripheral frontoparietal white matter.

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  • Widening spectrum of a reversible splenial lesion with transiently reduced diffusion

    J Takanashi, AJ Barkovich, T Shiihara, H Tada, M Kawatani, H Tsukahara, M Kikuchi, M Maeda

    AMERICAN JOURNAL OF NEURORADIOLOGY   27 ( 4 )   836 - 838   2006年4月

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    記述言語:英語   出版者・発行元:AMER SOC NEURORADIOLOGY  

    Four patients with encephalitis/encephalopathy and parenchymal lesions accompanying reversible splenial lesions were retrospectively evaluated. In 3 patients, reversible lesions with transiently reduced diffusion were seen in the splenium and symmetrically in the peripheral frontoparietal white matter, clinical signs and symptoms were mild, and recovery was complete. These and previous observations suggest a less severe course and outcome for patients with reversible lesions isolated to the splenium or to the splenium and peripheral frontoparietal white matter.

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  • Neonatal suppurative parotitis possibly associated with congenital cytomegalovirus infection and maternal methyldopa administration

    Y Todoroki, H Tsukahara, M Kawatani, Y Ohshma, KI Shukunami, F Kotsuji, M Mayumi

    PEDIATRICS INTERNATIONAL   48 ( 2 )   185 - 186   2006年4月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    DOI: 10.1111/j.1442-200X.2006.02188.x

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  • Urinary oxidative stress markers in young patients with type 1 diabetes

    Hata, I, M Kaji, S Hirano, Y Shigematsu, H Tsukahara, M Mayumi

    PEDIATRICS INTERNATIONAL   48 ( 1 )   58 - 61   2006年2月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    Background: Involvement of oxidative stress in the pathogenesis of diabetic vascular complications has been proposed. However, there are few methods to determine the status of oxidative stress both directly and quantitatively in young patients with type 1 diabetes.
    Methods: A total of 27 young patients with type 1 diabetes (mean age +/- SD, 12.6 +/- 4.2 years) with normal renal function and 38 healthy control subjects (13.0 +/- 4.6 years) were investigated. Early morning voiding urine samples were collected. The concentrations of acrolein-lysine adducts, 8-hydroxy-2&apos;-deoxyguanosine (8-OHdG) were determined using competitive enzyme-linked immunosorbent assay, and nitric oxide metabolites were measured using the colorimetric, non-enzymatic assay.
    Results: Urinary concentrations of 8-OHdG, but not acrolein-lysine adducts and nitric oxide metabolites, were significantly increased in the diabetic group. For diabetic patients, microalbuminuria was significantly correlated with higher concentrations of all three markers. Hemoglobin A(1c) values were significantly correlated with 8-OHdG values.
    Conclusion: These findings indicate that increased oxidative stress and the risk of vascular complications may be present at early stages of type 1 diabetes.

    DOI: 10.1111/j.1442-200X.2006.02156.x

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  • CoQ10の臨床的研究: 小児疾患とCoQ10

    徳力 周子, 塚原 宏一, 大嶋 勇成, 古畑 律代, 塚原 康代, 谷崎 崇, 太田 徳仁, 西井 学, 関根 恭一, 眞弓 光文

    機能姓食品と薬理栄養   3 ( 4 )   241 - 248   2006年

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    記述言語:日本語   出版者・発行元:(株)インフォノーツパブリッシング  

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  • 重症心身障害者における血清中セレンおよびチオレドキシンの計測

    佐藤 周子, 梶原 真清恵, 紫 英人, 竹内 元治, 塚原 宏一, 出口 洋二, 眞弓 光文

    小児科臨床   59 ( 6 )   1147 - 1151   2006年

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  • 小児における異常ナトリウム血症の管理

    塚原 宏一

    小児科臨床   59 ( 7 )   1543 - 1553   2006年

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  • 平成17年度小児科医会例会ミニシンポジウム(小児の画像診断)可逆性脳梁膨大部病変を伴う脳症・脳炎: 新しい疾患単位として

    塚原 宏一

    平成18年度福井県小児科医会会報   35   24 - 29   2006年

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  • Advanced glycation end-product formation from fetus to adolescence: A parameter for evaluating “carbonyl stress” status in humans

    H.Tsukahara, R.Kobata, S.Tamura, A.Hata, M.Mayumi, K.Nishijima, K.Shukunami, M.Ueno, H.Kawakami, M.Uchiyama, K.Sekine, M.Miura

    J Dev Nephrol   14 ( 1 )   42 - 48   2006年

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  • Hepatocyte growth factor concentration in umbilical cord blood

    R.Kobata, H.Tsukahara, M. Kawatani, K.Nishijima, K-I.Shukunami, F.Kotsuji, M.Ueno, M.Mayumi

    Medical Postgraduate   44 ( 4 )   415 - 417   2006年

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  • 一酸化窒素(NO)と腎臓: 個人的考察

    塚原 宏一

    小児腎臓病学会雑誌   19 ( 2 )   96 - 103   2006年

  • 新生児骨代謝の評価: 特に子宮収縮抑制剤の作用について

    徳力 周子, 塚原 宏一, 古畑 律代, 田村 知史, 眞弓 光文

    第23回小児代謝性骨疾患研究会発表論文集   13 - 17   2006年

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  • 初診時に左心房内への進展を呈していた胸膜肺芽腫の1例

    田村 知史, 金谷 由宇子, 塚原 宏一, 谷澤 昭彦, 眞弓 光文, 今村 好章

    日児誌   110 ( 12 )   1671 - 1675   2006年

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  • 糖尿病血管系合併症における分子機構の解明と治療戦略への応用

    塚原 宏一

    平成17年度科学研究費補助金実績報告書(基盤研究C)   2006年

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  • 平成17年度厚生労働科学研究費補助金(子ども家庭総合研究事業)総括研究報告書: 小児難治性腎尿路疾患の早期発見、診断管理・治療に関する研究(主任研究者 五十嵐隆)

    五十嵐 隆, 松山 健, 伊藤 雄平, 塚原 宏一, 中井 秀郎, 飯島 一誠, 塚口 裕康, 関根 孝司, 吉川 徳茂, 本田 雅敬, 服部 新三郎, 幡谷 浩志, 和田 尚弘

    平成17年度厚生労働科学研究費補助金(子ども家庭総合研究事業)総括・分担研究報告書   1 - 16   2006年

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  • 平成17年度厚生労働科学研究費補助金(子ども家庭総合研究事業)分担研究報告書: 小児難治性腎尿路疾患の早期発見、診断管理・治療に関する研究(主任研究者 五十嵐隆). 尿路感染症の診断、治療、管理システムの構築に関する研究

    塚原 宏一

    平成17年度厚生労働科学研究費補助金(子ども家庭総合研究事業)総括・分担研究報告書   2006年

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  • 糖尿病血管系合併症における分子機構の解明と治療戦略への応用

    塚原 宏一

    平成17年度科学研究費補助金実績報告書(基盤研究C)   2006年

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  • 超早産(在胎28週未満)で出生した児の水電解質代謝の評価とその制御: 輸液療法のガイドライン作成に向けて

    塚原 宏一, 古畑 律代

    福井大学重点研究成果報告書   128 - 129   2006年

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  • 平成17年度厚生労働科学研究費補助金(子ども家庭総合研究事業)総括研究報告書: 小児難治性腎尿路疾患の早期発見、診断管理・治療に関する研究(主任研究者 五十嵐隆)

    五十嵐 隆, 松山 健, 伊藤 雄平, 塚原 宏一, 中井 秀郎, 飯島 一誠, 塚口 裕康, 関根 孝司, 吉川 徳茂, 本田 雅敬, 服部 新三郎, 幡谷 浩志, 和田 尚弘

    平成17年度厚生労働科学研究費補助金(子ども家庭総合研究事業)総括・分担研究報告書   1 - 16   2006年

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  • 平成17年度厚生労働科学研究費補助金(子ども家庭総合研究事業)分担研究報告書: 小児難治性腎尿路疾患の早期発見、診断管理・治療に関する研究(主任研究者 五十嵐隆). 尿路感染症の診断、治療、管理システムの構築に関する研究

    塚原 宏一

    平成17年度厚生労働科学研究費補助金(子ども家庭総合研究事業)総括・分担研究報告書   2006年

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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年

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  • 胎児超音波検査でPotter sequenceを疑われ、出生後urosepsisの管理に難渋した多発性嚢胞腎の1女児例

    古畑 律代, 金谷 由宇子, 田村 知史, 徳力 周子, 塚原 宏一, 谷澤 昭彦, 平岡 政弘, 眞弓 光文, 西島 浩二, 宿南 憲一

    Pharma Medica   24 ( 5 )   126 - 129   2006年

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  • 骨形成不全症IIA型の乳児例

    早川 和代, 藤永 英志, 奥村 光祥, 中西 宏美, 三國 貴康, 横尾 憲孝, 濱畑 啓悟, 吉田 晃, 田中 里江子, 塚原 宏一, 百井 亨

    小児科臨床   59 ( 5 )   995 - 999   2006年

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  • Hepatocyte growth factor concentration in umbilical cord blood

    R.Kobata, H.Tsukahara, M. Kawatani, K.Nishijima, K-I.Shukunami, F.Kotsuji, M.Ueno, M.Mayumi

    Medical Postgraduate   44 ( 4 )   415 - 417   2006年

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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年

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  • 胎児超音波検査でPotter sequenceを疑われ、出生後urosepsisの管理に難渋した多発性嚢胞腎の1女児例

    古畑 律代, 金谷 由宇子, 田村 知史, 徳力 周子, 塚原 宏一, 谷澤 昭彦, 平岡 政弘, 眞弓 光文, 西島 浩二, 宿南 憲一

    Pharma Medica   24 ( 5 )   126 - 129   2006年

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  • 骨形成不全症IIA型の乳児例

    早川 和代, 藤永 英志, 奥村 光祥, 中西 宏美, 三國 貴康, 横尾 憲孝, 濱畑 啓悟, 吉田 晃, 田中 里江子, 塚原 宏一, 百井 亨

    小児科臨床   59 ( 5 )   995 - 999   2006年

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  • 【CoQ10の研究】CoQ10の臨床的研究 小児疾患とCoQ10

    徳力 周子, 塚原 宏一, 大嶋 勇成, 古畑 律代, 塚原 康代, 谷崎 崇, 太田 徳仁, 西井 学, 関根 恭一, 眞弓 光文

    機能性食品と薬理栄養   3 ( 4 )   241 - 248   2006年

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    記述言語:日本語   出版者・発行元:(株)インフォノーツパブリッシング  

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  • 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年12月

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    記述言語:日本語   出版者・発行元:金原出版  

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    その他リンク: http://search.jamas.or.jp/link/ui/2006081102

  • 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年11月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元: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-π in the urine of preterm neonates

    H.Tsukahara, M.Toyooka, Y.Kanaya, K.Ogura, M.Kawatani, A.Hata, M.Hiraoka, M.Mayumi

    Pediatr Int   47 ( 5 )   528 - 531   2005年10月

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

    Y.Mori, H.Tsukahara, MZ.Jiang, M.Mayumi

    Respir Med   99 ( 8 )   1068 - 1069   2005年8月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)  

    DOI: 10.1016/j.rmed.2005.01.011

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  • 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年7月

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    記述言語:英語   出版者・発行元: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&apos;-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-α-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

    Respir Med   99 ( 5 )   580 - 591   2005年5月

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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年5月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元: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年4月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    DOI: 10.1111/j.1442-200x.2005.02029.x

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  • 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年3月

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    記述言語:英語   出版者・発行元: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年2月

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    記述言語:英語   出版者・発行元: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年1月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    DOI: 10.1097/01.AOG.0000149162.89941.83

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  • 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年

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  • 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年

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  • 早産児の代謝性骨疾患

    塚原宏一

    周産期医学   35   1671 - 1679   2005年

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  • 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年

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  • 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年

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    記述言語:日本語   出版者・発行元:(株)東京医学社  

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  • 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年

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  • 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年

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  • 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年

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    記述言語:英語   出版者・発行元: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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  • 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年

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  • 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年

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  • 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年

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  • 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年

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  • 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年11月

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    記述言語:英語   出版者・発行元: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年8月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)   出版者・発行元:SPRINGER  

    DOI: 10.1007/s00247-004-1233-5

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  • 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年8月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

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  • 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年8月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

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  • 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年7月

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    記述言語:英語   出版者・発行元: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 Sci   75 ( 8 )   933 - 938   2004年7月

  • Effects of antioxidants and nitric oxide on TNF-α-induced cell adhesion molecule expression and NF-κB activation in human dermal microvascular endothelial cells

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

    Life Sci   75 ( 10 )   1159 - 1170   2004年7月

  • 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年6月

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    記述言語:英語   出版者・発行元: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 β2-microglobin excretion in premature newborns

    H.Tsukahara, M.Hiraoka, M.Mayumi

    J Pediatr   144 ( 6 )   835 - 836   2004年6月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)  

    DOI: 10.1016/j.jpeds.2004.02.039

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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年5月

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    記述言語:英語   出版者・発行元: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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  • Effects of antioxidant and nitric oxide on chemokine production in TNF-α-stimulated human dermal microvascular endothelial cells

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

    Free Radic Res   38 ( 5 )   473 - 480   2004年5月

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  • Endothelial dysfunction in Kawasaki disaese: Focus on nitric oxide

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

    Pediatr Int   46 ( 1 )   114 - 114   2004年2月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)  

    DOI: 10.1111/j.1328-0867.2004.01849.x

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  • 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年1月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING INC  

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  • 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年1月

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    記述言語:英語   出版者・発行元: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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  • 薬剤の胎児腎への影響: リトドリン、マグネシウム

    塚原宏一

    日本小児腎不全学会雑誌   24   30 - 34   2004年

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  • 新生児単純ヘルペスウイルス感染症を呈した超低出生体重児の1例

    早川 和代, 畑 郁江, 古畑 律代, 山田 直江, 川谷 正男, 金谷 由宇子, 塚原 宏一, 谷澤 昭彦, 眞弓 光文

    日児誌   108 ( 5 )   782 - 785   2004年

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  • 早産児の骨代謝マーカーとDXAを用いた骨量計測

    塚原宏一

    第4回新生児栄養フォーラム発表論文集   85-101   2004年

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  • アレルギーと酸化ストレス

    塚原 宏一, 眞弓 光文

    日児誌   108 ( 5 )   744 - 752   2004年

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  • Acute bilateral medial medullary infarction: A unique ‘heart appearance’ sign by diffusion-weighted imaging

    Maeda, M, Shimono, T, Tsukahara, H, Maier SE, Takeda, T

    Eur Neurol   51 ( 4 )   236 - 237   2004年

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  • Methylenetetrahydrofolate reductase polymorphism in patients with bronchial asthma

    MZ.Jiang, H.Tsukahara, Y.Ohshima, C.Zou, N.Ohta, S.Sato, Y.Todoroki, M.Hiraoka, M.Nambu, T.Tanaka, E.Yamaguchi, N.Kondo, M.Mayumi

    Int Med J   11 ( 2 )   119 - 123   2004年

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  • Mobilizationの責任

    塚原宏一

    平成16年度福井県小児科医会会報33号   177   2004年

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  • 小児疾患シリーズ(小児救急の手引き8): ショック

    塚原 宏一, 眞弓 光文

    臨床医薬   20 ( 7 )   795 - 805   2004年

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  • エンドセリン/エンドセリン受容体系の骨格系における生物学的役割

    塚原宏一

    第20回小児代謝性骨疾患研究会発表論文集   89 - 93   2004年

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  • An extremely low birthweight infant with metaphyseal osteopenia in long bones possibly due to maternal administration of magnesium sulphate

    H.Tsukahara, N.Yamada, H.Kometani, Y.Kanaya, N.Ohta, S.Sato, A.Tanizawa, M.Mayumi

    Repots for 21st Pediatric Metabolic Bone Disease Conference   45 - 48   2004年

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  • 壊死性腸炎を呈するミルクアレルギーの新生児症例についての検討

    塚原宏一

    小児科臨床   57(2)   273 - 276   2004年