基本情報
- 所属
- 自治医科大学 医学部小児科学講座 / 医学部小児科学講座 小児医学部門 教授
- 研究者番号
- 90426320
- J-GLOBAL ID
- 201401039803985369
- researchmap会員ID
- B000238601
- 外部リンク
経歴
10論文
354-
Scientific reports 14(1) 4820-4820 2024年2月27日Originally, apomorphine was a broad-spectrum dopamine agonist with an affinity for all subtypes of the Dopamine D1 receptor to the D5 receptor. We previously identified apomorphine as a potential therapeutic agent for mitochondrial diseases by screening a chemical library of fibroblasts from patients with mitochondrial diseases. In this study, we showed that apomorphine prevented ferroptosis in fibroblasts from various types of mitochondrial diseases as well as in normal controls. Well-known biomarkers of ferroptosis include protein markers such as prostaglandin endoperoxide synthase 2 (PTGS2), a key gene for ferroptosis-related inflammation PTGS2, lipid peroxidation, and reactive oxygen species. Our findings that apomorphine induced significant downregulation of PTSG2 and suppressed lipid peroxide to the same extent as other inhibitors of ferroptosis also indicate that apomorphine suppresses ferroptosis. To our knowledge, this is the first study to report that the anti-ferroptosis effect of apomorphine is not related to dopamine receptor agonist action and that apomorphine is a potent inhibitor of ferroptotic cell death independent of dopaminergic receptors.
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Journal of burn care & research : official publication of the American Burn Association 2024年2月14日Thermal airway injuries, usually accompanied by facial burns, require emergency management. We encountered a pediatric case of a late airway-scalding injury without any initial signs of scalding on the face or inside the oral cavity. A 16-month-old boy was accidentally exposed to boiling water from overhead and developed tachypnea and dyspnea at 8 h after the injury. When he visited our hospital at 12 h after the injury, there were no scalding-related findings on his face or inside his oral cavity; however, severe laryngeal edema was observed, which required emergency intubation. Thermal airway injuries can occur later, even if there is no evidence of facial or oral scalding immediately after the injury. Airway injuries should be considered when a patient has been exposed to hot water from overhead.
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Scientific reports 14(1) 440-440 2024年1月3日Menkes disease is an X-linked disorder of copper metabolism caused by mutations in the ATP7A gene, and female carriers are usually asymptomatic. We describe a 7-month-old female patient with severe intellectual disability, epilepsy, and low levels of serum copper and ceruloplasmin. While heterozygous deletion of exons 16 and 17 of the ATP7A gene was detected in the proband, her mother, and her grandmother, only the proband suffered from Menkes disease clinically. Intriguingly, X chromosome inactivation (XCI) analysis demonstrated that the grandmother and the mother showed skewing of XCI toward the allele with the ATP7A deletion and that the proband had extremely skewed XCI toward the normal allele, resulting in exclusive expression of the pathogenic ATP7A mRNA transcripts. Expression bias analysis and recombination mapping of the X chromosome by the combination of whole genome and RNA sequencing demonstrated that meiotic recombination occurred at Xp21-p22 and Xq26-q28. Assuming that a genetic factor on the X chromosome enhanced or suppressed XCI of its allele, the factor must be on either of the two distal regions derived from her grandfather. Although we were unable to fully uncover the molecular mechanism, we concluded that unfavorable switching of skewed XCI caused Menkes disease in the proband.
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Pediatrics international : official journal of the Japan Pediatric Society 66(1) e15761 2024年BACKGROUND: Behavioral problems of foster children are an important issue for the maintenance of the foster care system, but they have not been adequately studied in Japan. We used the Eyberg Child Behavior Inventory (ECBI) to investigate behavioral problems among foster children and to examine associated factors. METHODS: Twenty-nine foster children and their foster parents and 479 non-foster children and parents were recruited for the foster and control groups, respectively. Both groups underwent statistical comparative analyses using data from their ECBI assessments. The ECBI has two scales: the Intensity Scale quantifies the severity of child behavioral problems, and the Problem Scale captures the caregiver's perceived difficulties handling each behavior. We conducted a retrospective investigation of the background of the foster parent-child pairs to explore potential causal relationships with behavioral problems. RESULTS: The mean intensity score for the foster group was significantly higher than that for the control group (p = 0.001). The mean problem scores for the foster group and the control group were not significantly different (p = 0.79). In the foster group, the retrospective investigation revealed two children with neurological or neurodevelopmental disorders, 17 with histories of abuse, and 10 with other issues. CONCLUSION: Intensity scores showed severe behavioral problems among foster children, perhaps caused by neurological disorders, abuse, parental mental health, or economic hardship. Problem scores showed no significant differences between groups. It can therefore be posited that foster parents might exhibit a more lenient parenting style when dealing with children who have a history of abuse by their biological parents.
MISC
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Epileptic disorders : international epilepsy journal with videotape 22(2) 214-218 2020年4月16日Ring chromosome 20 syndrome is an epileptic and neurodevelopmental encephalopathy that occurs in children, characterised by a triad of refractory frontal lobe seizures, recurrent non-convulsive status epilepticus and frontal lobe-dominant paroxysmal discharges. However, details of other clinical features associated with ring chromosome 20 syndrome remain unknown. Here, we report two patients with ring chromosome 20 syndrome who had praxis-induced reflex seizures. Case 1 was an 11-year-old girl who presented with seizures triggered by specific activities such as mental and written calculations, writing, decision-making, recall, sudden changes in routine or ambient temperature and bathing. During calculations, left frontal lobe-dominant, 3-Hz slow-wave bursts were observed on EEG. Lacosamide effectively suppressed her tonic seizures. Case 2 was a six-year-old boy who presented with seizures triggered by specific activities such as calculations, recall and bathing. During calculations, frontal lobe-dominant, 3-Hz spike and slow-wave bursts were observed on EEG. Although his epilepsy was refractory, gabapentin reduced the frequency of focal seizures. In both cases, the hyperexcitability in the frontal lobe may have spread to the motor cortex and precipitated praxis-induced seizures. Therefore, in addition to the known characteristic triad, praxis-induced reflex seizures may also be a feature of ring chromosome 20 syndrome.
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HUMAN GENE THERAPY 28(12) A4-A4 2017年12月
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日本小児科学会雑誌 121(8) 1391-1396 2017年8月 査読有り3ヵ月男児。父と入浴中に心肺停止状態となり、救急隊による蘇生後、小児集中治療室へ搬送された。受傷機転不明の急性硬膜下血腫、眼底出血を認めたため虐待関連頭部外傷を疑ったが、入院時の問診では虐待を疑うエピソードを確認できなかった。びまん性脳浮腫を認めたため頸椎MRIを撮影し、Short Tau Inversion Recovery矢状断像にて項靱帯や棘間靱帯などの椎体支持組織および頸髄内部が高信号を示し、頸髄損傷を示唆する所見であった。後日、父が本児を強く揺さぶったことが確認され、乳幼児揺さぶられ症候群による上位頸髄損傷から呼吸停止および心肺停止状態に至ったと判断した。入院経過中、各種治療への反応は乏しく徐々に多臓器不全の状態を呈し、第41病日に死亡した。
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MOLECULAR THERAPY 25(5) 108-108 2017年5月
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日本小児科学会雑誌 121(5) 855-862 2017年5月インフルエンザ脳症発症例79例と未発症例2190例における臨床特徴を比較検討した。その結果、インフルエンザ脳症発症例と未発症例の間には年齢、最高体温、けいれん発現率と持続時間、脱力、末梢冷感の項目で有意差がみられた。また、急性脳症発症例の方が神経症状を介さず意識障害・けいれんに至る割合が有意に高い結果となり、一方で精神症状を発現した場合は非脳炎症例に比べて、せん妄の程度が有意に強くなることが明らかとなった。今回の検討から、4歳以下の低年齢、最高気温40°以上、けいれんの持続時間が15分以上、脱力や末梢の著しい冷感などがインフルエンザ脳症のリスクファクターとなる可能性が示唆された。
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HUMAN GENE THERAPY 27(11) A146-A147 2016年11月
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MITOCHONDRION 31 96-97 2016年11月
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HUMAN GENE THERAPY 27(11) A45-A45 2016年11月
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EXPERT OPINION ON ORPHAN DRUGS 3(12) 1447-1459 2015年12月Introduction: Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive disorder caused by mutations in the proteolipid protein 1 (PLP1) gene, which encodes PLP1 and DM20. PMD is characterized by a defect in myelin formation associated with PLP1 gene mutations (i.e., exonic and intronic mutations, duplication, or deletion of the entire gene). A combination of magnetic resonance imaging (MRI) and genetic testing is essential to diagnose PMD. The disease phenotype manifests due to the loss of PLP/DM20 function or the toxicity of mutant PLP/DM20 or overexpressed PLP/DM20.Areas covered: Potential approaches at the RNA level include restoring correct splicing with oligonucleotides and decreasing PLP1 expression using a transcriptional activator antagonist. Two approaches used in mouse models that have clinical potential include cholesterol supplementation and use of compounds that decrease the excessive unfolded protein response (UPR) in the endoplasmic reticulum (ER). Two types of cell-based therapy, bone marrow transplantation and stem cell engraftment, were recently employed safely in humans.Expert opinion: Elucidation of PMD pathophysiology has enabled several recent therapeutic approaches. Administration of cholesterol or curcumin in mouse models of PMD reportedly extends survival time. Stem cell therapies await evaluation of long-term effectiveness and safety in patients with PMD.
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こども医療センター医学誌 44(4) 254-255 2015年10月先天性大脳白質形成不全症は中枢神経系の髄鞘形成不全を示し、代表的な疾患にペリツェウス・メルツバッハ病Pelizaeus-Merzbacher Disease(PMD)が挙げられる。髄鞘構成の主なタンパク質がプロテオリピドプロテイン(PLP1)であり、PLP1タンパクの異常がPMDの原因である。現在国内では、100例程度の患者がいるとみられ、当センターでは国内で唯一保険診療としてPLP1の遺伝子解析を行っている。平成26年度は依頼15件中、変異は重複が3例、点変異が4例認められ、8例についてはPLP遺伝子に異常は認めなかった。(著者抄録)
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こども医療センター医学誌 44(3) 141-143 2015年7月治療可能な代謝疾患の一つにクレアチン代謝異常症があり、その診断においては、尿や血清中のクレアチン関連化合物(グアニジノ酢酸、クレアチン/クレアチニン比)を測定することで原因遺伝子を特定する手掛かりが得られる。著者等はこれまでに、高速液体クロマトグラフ(HPLC)-UV検出器を用いた生体試料中のクレアチン関連化合物測定法を開発しているが、その問題点として、尿中のクレアチン/クレアチニン比は感度良く測定できるものの、グアニジノ酢酸は正常2〜3倍以下の検出が難しかった。そこで今回、UV検出器の約1000倍の感度を持つ質量分析装置(MS)を使用し、その際、測定に用いるカラムを、UV検出器に使用していたShodex IC YS-50(ポリマー系ゲルの表面にカルボキシル基が結合したカラム)からShodex Asahipak NH2Pシリーズ(アミノ基が結合したカラム)に変更した。その結果、UV検出法の1/1000の単位ng/mLまで測定することが可能であった。
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「ミトコンドリア病診療の質を高める、レジストリシステムの構築、診断基準・診療ガイドラインの策定および診断システムの整備を行う臨床研究」に関する研究 平成26年度 委託業務成果報告書 2015年
共同研究・競争的資金等の研究課題
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