担当区分：責任著者   記述言語：英語   掲載種別：学位論文（博士）   出版者・発行元：Reproductive BioMedicine Online  

Research question: What is the proportion of infants born as a result of assisted reproductive technology ART across different types of neonatal critical congenital heart disease (CCHD) in a Japanese population? Design: A retrospective analysis of 418 consecutive infants with CCHD that required catheter treatment or surgery within the first 28 days of life or ductal-dependent lesions, in two paediatric centres in Japan, between January 2014 and December 2019. The proportion of ART in infants with each type of CCHD was evaluated. The proportion of ART in infants with univentricular heart defect (UVH) compared with those with biventricular heart defect (BVH) was evaluated. Results: The study group included 229 boys and 189 girls, with a gestational age of 38 ± 2 weeks. Overall, 61 infants (14.6%) were conceived by fertility treatment with 46 (11.0%) conceived by ART. Univentricular heart defect and BVH were identified in 111 infants (26.6%) and 307 infants (73.4%), respectively. The proportion of infants conceived by ART was significantly higher in UVH (16.2%) than in BVH (9.1%) (OR 2.28, 95% CI 1.11 to 4.68, P = 0.025), regardless of maternal age and maternal history of miscarriage. Conclusions: The proportion of ART in infants with CCHD, especially UVH, was high. These findings could form the basis of a rationale for carrying out fetal echocardiography in fetuses conceived by ART.

DOI： 10.1016/j.rbmo.2021.10.005

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記述言語：英語   出版者・発行元：Pediatrics International  

DOI： 10.1111/ped.15395

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PubMed

記述言語：英語   出版者・発行元：一般社団法人 日本循環器学会  

Background: The usefulness of electrocardiographic (ECG) voltage criteria for diagnosing hypertrophic cardiomyopathy (HCM) in pediatric patients is poorly defined. Methods and Results: ECGs at the 1st grade (mean [±SD] age 6.6±0.3 years) were available for 11 patients diagnosed with HCM at around the 7th grade (13.2±0.3 years). ECGs were available for another 64 patients diagnosed with HCM in the 1st (n=15), 7th (n=32), and 10th (n=17) grades. Fifty-one voltage criteria were developed by grade and sex using 62,841 ECGs from the general population. Voltage criteria were set at the 99.95th percentile (1/2,000) point based on the estimated prevalence of childhood HCM (2.9 per 100,000 [1/34,483]) to decrease false negatives. Conventional criteria were from guidelines for school-aged children in Japan. Of 11 patients before diagnosis, 2 satisfied conventional criteria in 1st grade; 5 (56%) of the remaining 9 patients fulfilled 2 voltage criteria (R wave in limb-lead I [RI]+S wave in lead V3 [SV3] and R wave in lead V3 [RV3]+SV3). Robustness analysis for sensitivity showed RV3+SV3 was superior to RI+SV3. For all patients after diagnosis, RI+SV4 was the main candidate. However, conventional criteria were more useful than voltage criteria. Conclusions: Early HCM prediction was possible using RV3+SV3 in >50% of patients in 1st grade. Voltage criteria may help diagnose prediagnostic or early HCM, and prevent tragic accidents, although further prospective studies are required.

DOI： 10.1253/circj.CJ-21-0376

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記述言語：英語   出版者・発行元：Pediatric Rheumatology  

Background: Tenascin-C (TN-C) is an extracellular matrix glycoprotein related to tissue inflammation. Our previous retrospective study conducted in 2016 revealed that the serum tenascin-C level was higher in patients with Kawasaki disease (KD) who were resistant to intravenous immunoglobulin (IVIG) and developed coronary artery lesions (CALs). The present study is a prospective cohort study to assess if the serum level of tenascin-C could be used as a novel biomarker to predict the risk of resistance to initial treatment for high-risk patients. Methods: A total of 380 KD patients were registered and provided serum samples for tenascin-C measurement before commencing their initial treatment. Patients who did not meet the inclusion criteria were excluded from analysis; of the 181 remaining subjects, there were 144 low-risk patients (Kobayashi score: ≤4 points) and 37 high-risk patients (Kobayashi score: ≥5 points). The initial treatments for low-risk patients and high-risk patients were conventional therapy (IVIG with aspirin) and prednisolone combination therapy, respectively. The patient clinical and laboratory data, including the serum tenascin-C level, were compared between initial treatment responders and non-responders. Results: In the low-risk patients, there was no significant difference in the median levels of serum tenascin-C between the initial therapy responders and non-responders. However, in the high-risk patients, the median serum tenascin-C level in initial therapy non-responders was significantly higher than that in initial therapy responders (175.8 ng/ml vs 117.6 ng/ml). Conclusions: Serum tenascin-C could be a biomarker for predicting the risk of high-risk patients being non-responsive to steroid combination therapy. Trial registration: This study was a prospective cohort study. It was approved by the ethics committee of each institute and performed in accordance with the Declaration of Helsinki.

DOI： 10.1186/s12969-021-00562-w

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Cardiology  

Background: A gain-of-function mutation in germline ABL1 causes a syndrome including congenital heart defects. However, the molecular mechanisms of this syndrome remain unknown. In this study, we found a novel ABL1 mutation in a Japanese family with ventricular septal defect, finger contracture, skin abnormalities and failure to thrive, and the molecular mechanisms of these phenotypes were investigated. Methods and results: Whole-exome sequencing on several family members revealed a novel mutation (c.1522A > C, p.I508L) in the tyrosine kinase domain of ABL1, and complete co-segregation with clinical presentations was confirmed in all members. Wild-type and mutant ABL1 were transfected into human embryonic kidney 293 cells for functional analysis. Western blotting confirmed that tyrosine phosphorylation in STAT5, a substrate of ABL1, was enhanced, and the novel mutation was proved to be a gain-of-function mutation. Since this novel mutation in ABL1 enhances tyrosine kinase activity, phosphorylated proteome analysis was used to elucidate the molecular pathology. The proteome analysis showed that phosphorylation in proteins such as UFD1, AXIN1, ATRX, which may be involved in the phenotypes, was enhanced in the mutant group. Conclusions: The onset of congenital heart defects associated with this syndrome appears to involve a mechanism caused by UFD1 common to 22q.11.2 deletion syndrome. On the other hand, AXIN1 and ATRX may be important in elucidating the mechanisms of other phenotypes, such as finger contracture and failure to thrive. Verification of these hypotheses would lead to further understanding of the pathophysiology and the development of treatment methods.

DOI： 10.1016/j.ijcard.2020.10.032

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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：Pediatrics International  

DOI： 10.1111/ped.14326

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Pulmonary Circulation  

The aim of this study was to investigate whether a dual endothelin receptor antagonist bosentan modulates the kinetics of bone marrow-derived stem cells in inhibiting the development of pulmonary hypertension. Bone marrow chimeric mice, transplanted with enhanced green fluorescent protein (eGFP)-positive bone marrow mononuclear cells, were exposed to hypobaric hypoxia or kept in the ambient air, and were daily treated with bosentan sodium salt or saline for 21 days. After the treatment period, right ventricular pressure was measured and pulmonary vascular morphometry was conducted. Incorporation of bone marrow-derived cells was analyzed by immunohistochemistry. Gene expression and protein level in the lung tissue were evaluated by quantitative real-time PCR and western blotting, respectively. The results showed that, in hypoxic mice, right ventricular pressure and the percentage of muscularized vessel were increased and pulmonary vascular density was decreased, each of which was reversed by bosentan. Bone marrow-derived endothelial cells and macrophages in lungs were increased by hypoxia. Bosentan promoted bone marrow-derived endothelial cell incorporation but inhibited macrophage infiltration into lungs. Quantitative real-time PCR analysis revealed that interleukin 6, stromal cell-derived factor-1, and monocyte chemoattractant protein-1 were upregulated by hypoxia, in which interleukin 6 and monocyte chemoattractant protein-1 were downregulated and stromal cell-derived factor-1 was upregulated by bosentan. Protein level of endothelial nitric oxide synthase (eNOS) in the whole lung was significantly upregulated by hypoxia, which was further upregulated by bosentan. Bosentan modulated kinetics of bone marrow-derived ECs and macrophages and related gene expression in lungs in ameliorating pulmonary hypertension in mice. Altered kinetics of bone marrow-derived stem cells may be a novel mechanism of the endothelin receptor blockade in vivo and confer a new understanding of the therapeutic basis for pulmonary hypertension.

DOI： 10.1177/2045894020919355

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Cardiology in the Young  

A pregnant woman was referred to our hospital due to fetal cardiomegaly. We recognised a dilated umbilical vein, which raised a suspicion of placental chorioangioma. A male neonate was delivered at 37 weeks of gestation. The cardiomegaly was gradually improved. Pathological examination identified five non-giant placental chorioangiomas. Multiple non-giant chorioangiomas may cause fetal complications despite the difficulty of prenatal diagnosis.

DOI： 10.1017/S1047951119002567

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Pediatrics International  

Background: The aim of this study was to investigate the prediction of postnatal prognosis using fetal and perinatal data in patients with primary congenital dilated cardiomyopathy (PCDCM), and to estimate the incidence of this disease. Methods: We examined correlations between fetal or perinatal data and postnatal clinical course in a multicenter retrospective study of eight patients with PCDCM. Incidence was calculated in a population-based study. Results: All patients developed heart failure at a median of 8 days (range, 0–43 days), and six patients died or required extracorporeal artificial heart therapy at a median of 67 days (range, 0–92 days). The cardiothoracic area ratio from fetal echocardiography, the Apgar score, and the standard deviation of birth weight correlated significantly with the date at onset of heart failure. However, no data correlated with survival. Cumulative incidence of PCDCM was calculated as 1.21 per 100 000 total births (95% confidence interval, 0.37 to 2.06). Conclusions: Primary congenital dilated cardiomyopathy has a poor prognosis, but cardiothoracic area ratio from fetal echocardiography, body weight at birth, and Apgar score correlate with the timing of the onset of heart failure, and these indicators might therefore be useful for peri- and postnatal management.

DOI： 10.1111/ped.14029

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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：Science Signaling  

Dysregulated bone morphogenetic protein (BMP) signaling in endothelial cells (ECs) is implicated in vascular diseases such as pulmonary arterial hypertension (PAH). Here, we showed that the transcription factor ATOH8 was a direct target of SMAD1/5 and was induced in a manner dependent on BMP but independent of Notch, another critical signaling pathway in ECs. In zebrafish and mice, inactivation of Atoh8 did not cause an arteriovenous malformation–like phenotype, which may arise because of dysregulated Notch signaling. In contrast, Atoh8-deficient mice exhibited a phenotype mimicking PAH, which included increased pulmonary arterial pressure and right ventricular hypertrophy. Moreover, ATOH8 expression was decreased in PAH patient lungs. We showed that in cells, ATOH8 interacted with hypoxia-inducible factor 2α (HIF-2α) and decreased its abundance, leading to reduced induction of HIF-2α target genes in response to hypoxia. Together, these findings suggest that the BMP receptor type II/ALK-1/SMAD/ATOH8 axis may attenuate hypoxic responses in ECs in the pulmonary circulation and may help prevent the development of PAH.

DOI： 10.1126/scisignal.aay4430

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Cardiology  

The authors regret that there was an error in the description of microdeletion in the family F in Table 1 and the Results section. The microdeletion in the family F was detected in the exons 6–33 as shown in Fig. 2, not exons 5–33 as published in Table 1 and Results section. In addition, we noted errata in the Fig. 3 of the manuscript. This figure summarized the previously reported data and the errata of the description of mutation and the numbering of references were noted. We incorporated the update for Fig. 3 and its legend as follows: The authors would like to apologise for any inconvenience caused.

DOI： 10.1016/j.ijcard.2019.06.020

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出版者・発行元：Journal of Human Genetics  

ORAI1 encodes a calcium channel essential in the store-operated calcium entry mechanism. A previous genetic association study identified a rare in-frame insertion variant of ORAI1 conferring Kawasaki disease (KD). To deepen our understanding of the involvement of rare variants of ORAI1 in KD pathogenesis, we investigated 3812 patients with KD and 2644 healthy individuals for variations in the protein-coding region of ORAI1. By re-sequencing the study participants’ DNA, 27 variants with minor allele frequencies (MAFs) < 0.01 that had not been examined in the previous study were identified. Although no significant association with KD was observed either in single-variant analyses or in a collapsing method analysis of the 27 variants, stratification by MAFs, variant types, and predicted deleteriousness revealed that six rare, deleterious, missense variants (MAF < 0.001, CADD C-score ≥ 20) were exclusively present in KD patients, including three refractory cases (OR = ∞, P = 0.046). The six missense variants include p.Gly98Asp, which has been demonstrated to result in gain of function leading to constitutive Ca2+ entry. Conversely, five types of frameshift variants, all identified near the N terminus and assumed to disrupt ORAI1 function, showed an opposite trend of association (OR = 0.35, P = 0.24). These findings support our hypothesis that genetic variations causing the upregulation of the Ca2+/NFAT pathway confer susceptibility to KD. Our findings also provide insights into the usefulness of stratifying the variants based on their MAFs and on the direction of the effects on protein function when conducting association studies using the gene-based collapsing method.

DOI： 10.1038/s10038-019-0588-2

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記述言語：日本語   出版者・発行元：特定非営利活動法人 日本小児循環器学会  

DOI： 10.9794/jspccs.35.132

CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1253/circj.CJ-66-0153

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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：JAMA Pediatrics  

IMPORTANCE Few studies with sufficient statistical power have shown the association of the z score of the coronary arterial internal diameter with coronary events (CE) in patients with Kawasaki disease (KD) with coronary artery aneurysms (CAA). OBJECTIVE To clarify the association of the z score with time-dependent CE occurrence in patients with KD with CAA. DESIGN, SETTING, AND PARTICIPANTS This multicenter, collaborative retrospective cohort study of 44 participating institutions included 1006 patients with KD younger than 19 years who received a coronary angiography between 1992 and 2011. MAIN OUTCOMES AND MEASURES The time-dependent occurrence of CE, including thrombosis, stenosis, obstruction, acute ischemic events, and coronary interventions, was analyzed for small (z score, <5), medium (z score,-5 to <10; actual internal diameter, <8 mm), and large (z score,-10 or-8 mm) CAA by the Kaplan-Meier method. The Cox proportional hazard regression model was used to identify risk factors for CE after adjusting for age, sex, size, morphology, number of CAA, resistance to initial intravenous immunoglobulin (IVIG) therapy, and antithrombotic medications. RESULTS Of 1006 patients, 714 (71%) were male, 341 (34%) received a diagnosis before age 1 year, 501 (50%) received a diagnosis between age 1 and 5 years, and 157 (16%) received a diagnosis at age 5 years or older. The 10-year event-free survival rate for CE was 100%, 94%, and 52%in men (P < .001) and 100%, 100%, and 75%in women (P < .001) for small, medium, and large CAA, respectively. The CE-free rate was 100%, 96%, and 79% in patients who were not resistant to IVIG therapy (P < .001) and 100%, 96%, and 51%in patients who were resistant to IVIG therapy (P < .001), respectively. Cox regression analysis revealed that large CAA (hazard ratio, 8.9; 95%CI, 5.1-15.4), male sex (hazard ratio, 2.8; 95%CI, 1.7-4.8), and resistance to IVIG therapy (hazard ratio, 2.2; 95%CI, 1.4-3.6) were significantly associated with CE. CONCLUSIONS AND RELEVANCE Classification using the internal diameter z score is useful for assessing the severity of CAA in relation to the time-dependent occurrence of CE and associated factors in patients with KD. Careful management of CE is necessary for all patients with KD with CAA, especially men and IVIG-resistant patients with a large CAA.

DOI： 10.1001/jamapediatrics.2018.0030

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記述言語：日本語   出版者・発行元：特定非営利活動法人 日本小児循環器学会  

<p><b>背景</b>：近年18トリソミーの先天性心疾患（CHD）に対する手術の報告が増加している．当院は在宅移行を目標として治療を行っているがCHD手術の経験はない．積極的な新生児治療下でのCHD手術非介入例の経過を検討する．</p><p><b>方法</b>：2005年4月から2015年12月に出生した18トリソミー計17例を対象とし，出生状況，生存率，在宅移行率，死亡原因などについて診療録に基づき後方視的に検討した．さらに心不全が症候化しうると考えられた肺血流増加型疾患のCHD例をLarge Shunt（LS）群として症状の有無を追加検討した．</p><p><b>結果</b>：全例にCHDを認めた．1年生存率64.7％，在宅移行率70.6％，退院日齢は16～285日（中央値129日）であった．死亡例の生存期間は0～1,054日（中央値104.5日）であった．LS群8例のうち5例（62.5％）が1年以上生存し，いずれも心不全は症候化しなかった．死亡3例のうち2例は心不全が原因と考えられた．</p><p><b>結論</b>：本検討ではCHD手術以外の標準的な新生児治療により，高い生存率・生存退院率が得られた．肺血流増加型のCHDを合併した18トリソミーは手術介入なく安定して経過する場合がある．肺血管閉塞性病変により生後の肺高血圧が持続することで，心不全が進行しなかったことが原因と考えられた．遠隔期の予後改善を目的としたCHD手術が有効であるかは明らかではなく，治療の選択肢として提案するにあたり，情報の蓄積が望まれる．</p>

DOI： 10.9794/jspccs.33.312

CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi:10.1016/j.echo.2016.03.017.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Congenital Heart Disease  

Background: There is no gold standard sedation method for pediatric cardiac catheterization. In congenital heart diseases with intracardiac shunts, hemodynamic parameters are prone to change depending on the ventilation conditions and anesthetics, although few studies have examined these effects. The purpose of this study was to investigate the effects of two different sedation methods on the hemodynamic parameters. Methods: This study retrospectively evaluated consecutive patients with ventricular septal defect (VSD) below 1 year of age who underwent cardiac catheterization at Aichi Children’s Health and Medical Center, who were divided into age-and VSD diameter-matched general anesthesia (GA) and monitored anesthesia care (MAC) under the natural airway groups (n = 40 each), for comparison of hemodynamic parameters. Results: In the GA group, arterial blood pH and arterial partial pressure of oxygen were significantly higher (p < 0.01), whereas arterial partial pressure of carbon dioxide was significantly lower than in the MAC group (p < 0.01). Mean pulmonary artery pressure (p < 0.05) and systemic blood pressure (p < 0.01) were lower in the GA group. Pulmonary vascular resistance index (p < 0.01) and systemic vascular resistance index (p < 0.01) were also significantly lower in the GA group than the MAC group. There were no significant differences in pulmonary blood flow index, systemic blood flow index, and pulmonary/systemic blood flow ratio between the two groups. Conclusions: Cardiac catheterization under GA in VSD patients results in different hemodynamic parameters compared to that under MAC. In par-ticular, when using pulmonary artery pressure and pulmonary vascular resistance measured under GA for judg-ment regarding the surgical indications or perioperative management, consideration should be given to the fact that these parameters might be lower compared to those measured under MAC.

DOI： 10.32604/chd.2023.027590

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers in Pediatrics  

Pulmonary hypertension (PH) with developmental lung disease is a life-threatening disease and accounts for 10%–12% of pediatric PH patients. Administration of specific pulmonary vasodilators to pediatric PH patients has brought about improvement of their long-term prognosis. Intravenous epoprostenol therapy is a gold standard therapy for severe idiopathic pulmonary arterial hypertension (IPAH), but there are few reports demonstrating the efficacy of epoprostenol for pediatric PH patients with developmental lung disease, especially when treating with high doses of epoprostenol. Two cases of pediatric PH patients with alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) and congenital diaphragmatic hernia (CDH) with bronchopulmonary dysplasia (BPD), respectively, treated with epoprostenol above 100 ng/kg/min are presented. In these two cases, severe PH was improved significantly by an aggressive increase of the epoprostenol infusion rate with administration of oral pulmonary vasodilators and appropriate respiratory management, without any significant adverse effects. High-dose epoprostenol therapy may be one of the therapeutic options in pediatric PH patients with developmental lung disease.

DOI： 10.3389/fped.2023.1116434

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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.jtct.2021.05.017

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Allergy and Clinical Immunology  

Background: Type I interferonopathies are a recently established subgroup of autoinflammatory diseases caused by mutations in genes associated with proteasome degradation or cytoplasmic RNA- and DNA-sensing pathways. Objective: This study aimed to unveil the molecular pathogenesis of a patient with novel type I interferonopathy, for which no known genetic mutations have been identified. Methods: We performed the whole-exome sequencing of a 1-month-old boy with novel type I interferonopathy. We also investigated proteasome activities using patient-derived B lymphoblastoid cell lines (LCLs) and normal LCLs transduced with the mutant gene. Results: Whole-exome sequencing identified a de novo proteasome 20S subunit beta 9 (PSMB9) p.G156D mutation in the patient who developed fever, a chilblain-like skin rash, myositis, and severe pulmonary hypertension due to the hyperactivation of IFN-α. Patient-derived LCLs revealed reduced proteasome activities, and exogenous transduction of mutant PSMB9 p.G156D into normal LCLs significantly suppressed proteasome activities, and the endogenous PSMB9 protein was lost along with the reduction of other immunoproteasome subunits, PSMB8 and PSMB10 proteins. He responded to the administration of a Janus kinase inhibitor, tofacitinib, and he was successfully withdrawn from venoarterial extracorporeal membranous oxygenation. At age 7 months, he received an unrelated cord blood transplantation. At 2 years posttransplantation, he no longer required tofacitinib and experienced no disease recurrence. Conclusions: We present the case of a patient with a novel type I interferonopathy caused by a de novo PSMB9 p.G156D mutation that suppressed the wild-type PSMB9 protein expression. Janus kinase inhibitor and stem cell transplantation could be curative therapies in patients with severe interferonopathies.

DOI： 10.1016/j.jaci.2021.03.010

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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：BMC Pediatrics  

Background: Kawasaki disease (KD) is an idiopathic systemic vasculitis that predominantly damages coronary arteries in children. Various pathogens have been investigated as triggers for KD, but no definitive causative pathogen has been determined. As KD is diagnosed by symptoms, several days are needed for diagnosis. Therefore, at the time of diagnosis of KD, the pathogen of the trigger may already be diminished. The aim of this study was to explore comprehensive pathogens in the sera at the acute stage of KD using high-throughput sequencing (HTS). Methods: Sera of 12 patients at an extremely early stage of KD and 12 controls were investigated. DNA and RNA sequences were read separately using HTS. Sequence data were imported into the home-brew meta-genomic analysis pipeline, PATHDET, to identify the pathogen sequences. Results: No RNA virus reads were detected in any KD case except for that of equine infectious anemia, which is known as a contaminant of commercial reverse transcriptase. Concerning DNA viruses, human herpesvirus 6B (HHV-6B, two cases) and Anelloviridae (eight cases) were detected among KD cases as well as controls. Multiple bacterial reads were obtained from KD and controls. Bacteria of the genera Acinetobacter, Pseudomonas, Delfita, Roseomonas, and Rhodocyclaceae appeared to be more common in KD sera than in the controls. Conclusion: No single pathogen was identified in serum samples of patients at the acute phase of KD. With multiple bacteria detected in the serum samples, it is difficult to exclude the possibility of contamination; however, it is possible that these bacteria might stimulate the immune system and induce KD.

DOI： 10.1186/s12887-020-02380-7

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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：Pediatrics International  

DOI： 10.1111/ped.14252

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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：Cytotherapy  

Perinatal bronchopulmonary dysplasia (BPD) is defined as lung injury in preterm infants caused by various factors, resulting in serious respiratory dysfunction and high mortality. The administration of mesenchymal stem/stromal cells (MSCs) to treat/prevent BPD has proven to have certain therapeutic effects. However, MSCs can only weakly regulate macrophage function, which is strongly involved in the development of BPD. 7ND-MSCs are MSCs transfected with 7ND, a truncated version of CC chemokine ligand 2 (CCL2) that promotes macrophage activation, using a lentiviral vector. In the present study, we show in a BPD rat model that 7ND-MSC administration, but not MSCs alone, ameliorated the impaired alveolarization evaluated by volume density and surface area in the lung tissue, as well as pulmonary artery remodeling and pulmonary hypertension induced by BPD. In addition, 7ND-MSCs, but not MSCs alone, reduced M1 macrophages and the messenger RNA expressions of interleukin-6 and CCL2 in the lung tissue. Thus, the present study showed the treatment effect of 7ND-MSCs in a BPD rat model, which was more effective than that of MSCs alone.

DOI： 10.1016/j.jcyt.2020.01.009

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担当区分：筆頭著者,　最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：一般社団法人 日本循環器学会  

DOI： 10.1253/circj.CJ-20-0139

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CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：一般社団法人 インターナショナル・ハート・ジャーナル刊行会  

Percutaneous occlusion of atrial septal defect (ASD) has recently become a standard therapeutic strategy, but little is known about left atrial (LA) function thereafter. The present study aimed to determine LA function in 43 children with ASD and 13 controls based on LA strain measured by two-dimensional echocardiographic speckle tracking (2DE-ST). Among these children, 12 underwent surgery (ASD-S), 31 had device closure (ASD-D), and 13 were included as controls. LA strain was significantly decreased after ASD-D but was not significantly altered after ASD-S, indicating that percutaneous occlusion of an ASD might decrease LA function. Furthermore, the size of the ASD device negatively correlated with LA strain. These results imply that ASD occlusion devices negatively influence LA function and might be important when decided therapeutic strategies for ASD. LA strain measured by 2DE-ST should become a good indicator of LA function after ASD treatment in children.

DOI： 10.1536/ihj.19-173

Web of Science

Scopus

PubMed

CiNii Research

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

A 14-year-old girl suddenly developed ventricular tachycardia and severe chest pain during hospitalisation for trauma surgery. CT revealed a needle in the pericardium. Careful interview elicited that she had inserted the needle by herself, and Munchausen syndrome was diagnosed. This is the first report of ventricular tachycardia caused by a foreign body in a patient with Munchausen syndrome.

DOI： 10.1017/S1047951119001744

Web of Science

Scopus

PubMed

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

Major aortopulmonary collateral arteries (MAPCAs) are unique vessels associated with hypoxia induced by congenital heart disease (CHD). Although MAPCAs are essential to supply blood to the lungs, their development and proliferation can induce life-threatening complications, such as rupture into the lung. Here, we describe a rare case of esophageal bleeding from MAPCAs in a CHD patient, which was successfully treated by transcatheter arterial embolization (TAE). A 16-year-old male with CHD experienced a hematemesis and melena after the Bentall procedure to treat valvular heart disease. Emergent esophagogastroduodenoscopy revealed spurting bleeding from the middle esophageal vessels; accordingly, endoscopic variceal ligation (EVL) was performed. However, he had a hematemesis again after 2 weeks of EVL. The arterial phase of dynamic computed tomography indicated that a MAPCA associated with CHD was the origin of bleeding. Hence, TAE of this MAPCA with a mixture of n-butyl-2-cyanoacrylate and ethiodized oil was performed to prevent re-bleeding. Color Doppler mode in endoscopic ultrasonography via the esophagus revealed mosaic-like signals in MAPCAs located in the esophageal wall. This finding was consistent with tortuous MAPCAs accompanied by turbulent blood flow. When clinicians encounter CHD patients with unexpected massive esophageal bleeding, bleeding related to MAPCAs should be considered.

DOI： 10.1007/s12328-018-0895-8

Web of Science

Scopus

PubMed

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

Background: Supravalvular aortic stenosis (SVAS) is a congenital heart disease affecting approximately 1:25,000 live births. SVAS may occur sporadically, be inherited in an autosomal dominant manner, or be associated with Williams-Beuren syndrome, a complex developmental disorder caused by a microdeletion of chromosome 7q11.23. ELN on 7q11.23, which encodes elastin, is the only known gene to be recurrently mutated in less than half of SVAS patients. Methods: Whole-exome sequencing (WES) was performed for seven familial SVAS families to identify other causative gene mutations of SVAS. Results: Three truncating mutations and three intragenic deletions affecting ELN were identified, yielding a diagnostic efficiency of 6/7 (85%). The deletions, which explained 3/7 of the present cohort, spanned 1–29 exons, which might be missed in the course of mutational analysis targeting point mutations. The presence of such deletions was validated by both WES-based copy number estimation and multiplex ligation-dependent probe amplification analyses, and their pathogenicity was reinforced by co-segregation with clinical presentations. Conclusions: The majority of familial SVAS patients appear to carry ELN mutations, which strongly indicates that elastin is the most important causative gene for SVAS. The frequency of intragenic deletions highlights the need for quantitative tests to analyze ELN for efficient genetic diagnosis of SVAS.

DOI： 10.1016/j.ijcard.2018.09.032

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Scopus

PubMed

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

Myocarditis is an inflammatory disease of the myocardium and leads to cardiac dysfunction and heart failure. Although viral infections are considered to be the most common etiology of myocarditis, the identification of the causative virus is still challenging. Recently, next-generation sequencing (NGS) has been applied in the diagnosis of infectious diseases. The aim of the current study was to comprehensively analyze potential pathogenic microorganisms using NGS in the sera of patients with myocarditis. Twelve pediatric and five adult patients hospitalized for acute myocarditis were included. Serum samples in the acute phase were obtained and analyzed using NGS to detect pathogen-derived DNA and RNA. Viral sequence reads were detected in 7 (41%) of the 17 myocarditis patients by NGS. Among these patients, detection of Epstein-Barr virus, human parvovirus B19, torque teno virus, and respiratory syncytial virus reads by NGS was consistent with polymerase chain reaction or antigen test results in one patient each. A large number of human pegivirus reads were detected from one patient by RNA sequencing; however, its pathogenicity to human is unknown. Conversely, the number of detected virus-derived reads was small in most cases, and the pathophysiological role of these viruses remains to be clarified. No significant bacterial or fungal reads other than normal bacterial flora was detected. These data indicate that comprehensive detection of virus-derived DNA and RNA using NGS can be useful for the identification of potential pathogenic viruses in myocarditis.

DOI： 10.1002/jmv.25263

Web of Science

Scopus

PubMed

記述言語：日本語   出版者・発行元：(NPO)日本小児循環器学会  

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

We compared the efficacy and safety of infliximab with intravenous immunoglobulin (IVIG), a standard therapy, in a phase 3 trial (NCT01596335) for Japanese patients with Kawasaki disease (KD) showing persistent fever after initial IVIG. Patients with initial IVIG-refractory KD, aged 1-10 years, received a single dose of IV infliximab 5 mg/kg or IV polyethylene glycol-treated human immunoglobulin (VGIH) 2 g/kg on day 0. Primary outcome was defervescence rate within 48 h after the start of treatment. Safety was evaluated through day 56. Overall, 31 patients were randomized (infliximab, n = 16; VGIH, n = 15); 31.3% and 60.0% patients discontinued due to worsening KD. Defervescence rate within 48 h was greater with infliximab (76.7%) than VGIH (37.0%) (p = 0.023), and defervescence was achieved earlier with infliximab (p = 0.0072). Coronary artery lesions occurred in 1 (6.3%) and 3 (20.0%) patients receiving infliximab and VGIH, respectively, up to day 21. Adverse events occurred in 15 (93.8%) and 15 (100.0%) patients in the infliximab and VGIH groups, respectively. No serious adverse events in the infliximab group and one in the VGIH group were observed. Infliximab improved the defervescence rate within 48 h and time to defervescence versus standard therapy, and was well tolerated in patients with IVIG-refractory KD.

DOI： 10.1038/s41598-017-18387-7

Scopus

PubMed

記述言語：英語   出版者・発行元：一般社団法人 インターナショナル・ハート・ジャーナル刊行会  

The use of unilateral pulmonary artery occlusion (UPAO) test for the preoperative evaluation of pneumonectomy was reported in adult patients. On the contrary, in infants, no strategies have yet been recommended to predict hemodynamics after pneumonectomy, nor has use of the UPAO test been reported. We describe the first case of infant with abnormal pulmonary circulation in whom successful pneumonectomy was performed after preoperative evaluation using UPAO test. Right pneumonectomy was planned for an 8-month-old girl, because of decreased right pulmonary function, high risk of pneumothorax, and impaired left lung expansion due to overexpansion caused by severe left bronchial stenosis and bronchomalacia. However, she had also prolonged pulmonary hypertension and there was difficulty in accurate echocardiographic evaluation of its severity due to concomitant left pulmonary artery stenosis. Furthermore, contrast-enhanced computer tomography suggested a certain degree of right pulmonary venous flow, discordant with the result showing scarce right pulmonary flow in perfusion scintigraphy. Predicting postoperative hemodynamic changes was therefore considered difficult. To evaluate these concerns, we performed cardiac catheterization and UPAO test to simulate postoperative hemodynamics. Pulmonary arteriography showed decreased but significant right pulmonary arterial and venous flows. Measurements including pulmonary artery pressure and cardiac index showed no marked changes after occlusion. Based on UPAO test results, the operation was successfully performed and hemodynamics remained stable postoperatively. The UPAO test may be useful for infants with cardiopulmonary impairment to evaluate the tolerability of pneumonectomy.

DOI： 10.1536/ihj.16-606

Scopus

PubMed

CiNii Research

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   出版者・発行元：特定非営利活動法人 日本小児循環器学会  

DOI： 10.9794/jspccs.33.247

CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jiac.2016.06.011.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.echo.2016.03.017. Epub 2016 Jun 7.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi:10.1371/journal.pone.0118655.

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語 著書種別：学術書

記述言語：日本語

記述言語：日本語

記述言語：英語

Missense mutations in the PTPN11 as a cause of cardiac defects associated with Noonan syndrome.

総ページ数：5   担当ページ：99－103   記述言語：日本語 著書種別：学術書

記述言語：日本語

開催年月日： 2021年7月

記述言語：英語   会議種別：口頭発表（招待・特別）  

開催地：奈良  

開催年月日： 2021年2月

記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

開催地：オンライン  

開催年月日： 2020年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：京都  

開催年月日： 2020年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催年月日： 2019年11月

記述言語：英語   会議種別：ポスター発表  

開催年月日： 2018年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催年月日： 2018年10月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催年月日： 2018年10月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催年月日： 2018年6月

記述言語：英語   会議種別：口頭発表（一般）  

開催年月日： 2023年11月

記述言語：英語   会議種別：ポスター発表  

開催地：Philadelphia   国名：アメリカ合衆国  

開催年月日： 2023年11月

記述言語：英語   会議種別：ポスター発表  

開催地：Dublin   国名：アイルランド  

開催年月日： 2023年9月

記述言語：日本語   会議種別：口頭発表（招待・特別）  

開催年月日： 2023年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2023年7月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催年月日： 2023年2月

記述言語：日本語   会議種別：口頭発表（招待・特別）  

開催年月日： 2022年12月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：横浜  

開催年月日： 2022年9月

記述言語：日本語   会議種別：口頭発表（招待・特別）  

開催地：オンライン  

開催年月日： 2022年7月

記述言語：日本語   会議種別：口頭発表（招待・特別）  

開催地：東京  

開催年月日： 2022年7月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催地：札幌  

開催年月日： 2022年4月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：郡山  

開催年月日： 2021年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催地：オンライン  

開催年月日： 2021年7月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催年月日： 2021年5月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：オンライン  

開催年月日： 2020年10月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2020年9月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2019年11月

記述言語：英語   会議種別：ポスター発表  

開催年月日： 2019年10月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催年月日： 2019年6月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2019年6月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2019年6月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2018年7月

記述言語：日本語   会議種別：ポスター発表  

開催年月日： 2018年7月

記述言語：日本語   会議種別：ポスター発表  

開催年月日： 2018年6月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2018年6月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2018年4月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催年月日： 2018年2月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2018年2月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2012年7月

記述言語：日本語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 2012年2月

記述言語：英語   会議種別：ポスター発表  

国名：日本国  

開催年月日： 2011年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：福岡   国名：日本国  

開催年月日： 2010年7月

記述言語：英語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 2009年11月

記述言語：英語   会議種別：ポスター発表  

開催年月日： 2009年6月

記述言語：英語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 2009年3月

記述言語：英語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 2008年11月

記述言語：英語   会議種別：ポスター発表  

開催年月日： 2007年7月

記述言語：日本語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 2006年7月

記述言語：日本語   会議種別：ポスター発表  

国名：日本国  

開催年月日： 2005年7月

記述言語：日本語   会議種別：ポスター発表  

国名：日本国  

開催年月日： 2004年6月

記述言語：日本語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 2002年7月

記述言語：日本語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 2001年9月

記述言語：英語   会議種別：口頭発表（一般）  

開催年月日： 2001年3月

記述言語：日本語   会議種別：ポスター発表  

国名：日本国  

開催年月日： 1997年11月

記述言語：日本語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 1997年9月

記述言語：日本語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 1996年12月

記述言語：日本語   会議種別：口頭発表（一般）  

国名：日本国  

小児循環器病学一般の総説

先天性心疾患の血行動態シミュレーションを通じた病態考察

臨床実習

小児循環器病学一般の総説

救急・治療および循環器疾患を担当

小児循環器疾患分野を担当

小児循環器疾患分野を担当

小児循環器病学を担当

小児循環器病学を担当

救急・治療および循環器疾患を担当

小児循環器疾患分野を担当

小児循環器疾患分野を担当

小児循環器病学を担当

救急・治療および循環器疾患を担当

小児循環器疾患分野を担当

小児循環器疾患分野を担当

小児循環器疾患分野を担当

救急・治療および循環器疾患を担当

小児循環器疾患分野を担当

小児循環器病学を担当

救急・治療および循環器疾患を担当

小児循環器疾患分野を担当

小児循環器疾患分野を担当

小児循環器病学を担当

小児循環器疾患分野を担当

救急・治療および循環器疾患を担当

小児循環器疾患分野を担当