PubMed | Red Cross, Saitama University, JR Sendai Hospital, Miyanosawa Koike Child Clinic and 30 more.
Type: | Journal: Diabetic medicine : a journal of the British Diabetic Association | Year: 2016
To examine the contribution of the FUT2 gene and ABO blood type to the development of Type 1 diabetes in Japanese children.We analysed FUT2 variants and ABO genotypes in a total of 531 Japanese children diagnosed with Type 1 diabetes and 448 control subjects. The possible association of FUT2 variants and ABO genotypes with the onset of Type 1 diabetes was statistically examined.The se2 genotype (c.385A>T) of the FUT2 gene was found to confer susceptibility to Type 1A diabetes in a recessive effects model [odds ratio for se2/se2, 1.68 (95% CI 1.20-2.35); corrected P value = 0.0075].The FUT2 gene contributed to the development of Type 1 diabetes in the present cohort of Japanese children. This article is protected by copyright. All rights reserved.
Inoue H.,Tokushima University |
Kangawa N.,Tokushima University |
Kinouchi A.,Tokushima University |
Sakamoto Y.,Tokushima University |
And 6 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011
Context: Short stature (SS) is a multifactorial developmental condition with a significant genetic component. Recent studies have revealed that rare deleterious mutations in the GH-secretagogue receptor type 1A (GHSR1A) gene could be a cause of familial SS or GH deficiency. Objective: The aim of this study was to evaluate the contribution of GHSR1A mutations to the molecular mechanism underlying SS in Japanese subjects. Methods: We performed mutational screening of the GHSR1A gene in 127 unrelated Japanese SS patients diagnosed with either isolated GH deficiency or idiopathic SS. Identified mutations were analyzed in 188 control subjects, and their functional properties were examined in a heterologous expression system. Results: Four novel heterozygous GHSR1A mutations were identified (ΔQ36, P108L, C173R, and D246A). Expression studies demonstrated that these mutations had varying functional consequences: 1) all mutations showed a loss-of-function effect on the constitutive signaling activity of GHSR1A, but the degree of loss varied widely; 2) C173R caused intracellular retention of the mutated protein, resulting in total loss of receptor function; 3) P108L resulted in a large decrease in binding affinity to ghrelin, without affecting its surface expression; 4) D246A uniquely impaired agonist- and inverse agonist-stimulated receptor signaling; and 5) ΔQ36 showed only a subtle reduction in constitutive activity. The cumulative frequency of these putative functional mutations wassignificantly higher in the patient group than in controls (4.72 vs. 0.53%; P=0.019; odds ratio=9.28; 95% confidence interval, 1.10-78.0). Conclusions: Our results suggest that GHSR1A mutations contribute to the genetic etiology of SS in the Japanese population. Copyright © 2011 by The Endocrine Society.
PubMed | Red Cross, Japan Synchrotron Radiation Research Institute, National Medical Center for Children and Mothers, Jikei University School of Medicine and 3 more.
Type: | Journal: Pediatric cardiology | Year: 2016
Structural examination of human heart specimens at the microscopic level is a prerequisite for understanding congenital heart diseases. It is desirable not to destroy or alter the properties of such specimens because of their scarcity. However, many of the currently available imaging techniques either destroy the specimen through sectioning or alter the chemical and mechanical properties of the specimen through staining and contrast agent injection. As a result, subsequent studies may not be possible. X-ray phase-contrast tomography is an imaging modality for biological soft tissues that does not destroy or alter the properties of the specimen. The feasibility of X-ray phase-contrast tomography for the structural examination of heart specimens was tested using infantile and fetal heart specimens without congenital diseases. X-ray phase-contrast tomography was carried out at the SPring-8 synchrotron radiation facility using the Talbot grating interferometer at the bending magnet beamline BL20B2 to visualize the structure of five non-pretreated whole heart specimens obtained by autopsy. High-resolution, three-dimensional images were obtained for all specimens. The images clearly showed the myocardial structure, coronary vessels, and conduction bundle. X-ray phase-contrast tomography allows high-resolution, three-dimensional imaging of human heart specimens. Intact imaging using X-ray phase-contrast tomography can contribute to further structural investigation of heart specimens with congenital heart diseases.
Morota N.,Tokyo Metropolitan Childrens Medical Center |
Ihara S.,Tokyo Metropolitan Childrens Medical Center |
Ogiwara H.,National Medical Center for Children and Mothers
Neurologia Medico-Chirurgica | Year: 2015
A paradigm shift is currently ongoing in the treatment of spasticity in childhood in Japan. Functional posterior rhizotomy (FPR), which was first introduced to Japan in 1996, is best indicated for children with spastic cerebral palsy, regardless of the clinical severity of spasticity. Surgery is generally carried out in the cauda equina, where the posterior root is separated from the anterior one, and neurophysiological procedures are used to judge which nerve root/rootlet should be cut. The outcome of FPR is favorable for reducing spasticity in the long-term follow-up. Intrathecal baclofen (ITB) treatment for childhood spasticity was approved in 2007 in Japan and the number of children undergoing ITB pump implantation has been gradually increasing. ITB treatment is best indicated for children with severe spasticity, especially those with dystonia, regardless of the pathological background. Since it is a surgery performed to implant foreign bodies, special attention should be paid to avoid perioperative complications such as CSF leakage, meningitis, and mechanical failure. Severely disabled children with spasticity would benefit most from ITB treatment. We would especially like to emphasize the importance of a strategic approach to the treatment of childhood spasticity. The first step is to reduce spasticity by FPR, ITB, and botulinum toxin injection. The second step is to aim for functional improvement after controlling spasticity. Traditional orthopedic surgery and neurorehabilitation form the second step of treatment. The combination of these treatments that allows them to complement each other is the key to a successful treatment of childhood spasticity. © 2015, Japan Neurosurgical Society. All rights reserved.
Gu Y.-H.,Teikyo University |
Yokoyama K.,Jichi Medical University |
Mizuta K.,Jichi Medical University |
Tsuchioka T.,Dokkyo Medical University |
And 6 more authors.
Journal of Pediatrics | Year: 2015
Objective To evaluate the sensitivity and specificity of a stool color card used for a mass screening of biliary atresia conducted over 19 years. In addition, the age at Kasai procedure and the long-term probabilities of native liver survival were investigated. Study design From 1994 to 2011, the stool color card was distributed to all pregnant women in Tochigi Prefecture, Japan. Before or during the postnatal 1-month health checkup, the mothers returned the completed stool color card to the attending pediatrician or obstetrician. All suspected cases of biliary atresia were referred for further examination. Diagnosis was confirmed by laparotomy or operative cholangiography for high-risk cases before the Kasai procedure. Patients with biliary atresia were followed from the date of their Kasai procedure until liver transplantation, death, or October 31, 2013, whichever comes sooner. Results A total of 313 230 live born infants were screened; 34 patients with biliary atresia were diagnosed. The sensitivity and specificity of stool color card screening at the 1-month check-up was 76.5% (95% CI 62.2-90.7) and 99.9% (95% CI 99.9-100.0), respectively. Mean age at the time of Kasai procedure was 59.7 days. According to Kaplan-Meier analysis, the native liver survival probability at 5, 10, and 15 years was 87.6%, 76.9%, and 48.5%, respectively. Conclusions The sensitivity and specificity of the stool color card have been demonstrated by our 19-year cohort study. We found that the timing of Kasai procedure and long-term native liver survival probabilities were improved, suggesting the beneficial effect of stool color card screening. Copyright © 2015 Elsevier Inc. All rights reserved.
PubMed | Tohoku University, Nagoya City University and National Medical Center for Children and Mothers
Type: | Journal: The Journal of pediatrics | Year: 2016
To ascertain a molecular genetic diagnosis for subjects with neonatal/infantile intrahepatic cholestasis (NIIC) by the use of next-generation sequencing (NGS) and to perform a genotype-phenotype correlation.We recruited Japanese subjects with NIIC who had no definitive molecular genetic diagnosis. We developed a diagnostic custom panel of 18 genes, and the amplicon library was sequenced via NGS. We then compared clinical data between the molecular genetically confirmed subjects with NIIC.We analyzed 109 patients with NIIC (genetic cholestasis, 31 subjects; unknown with complications such as prematurity, 46 subjects; unknown without complications, 32 subjects), and a molecular genetic diagnosis was made for 28 subjects (26%). The rate of positive molecular genetic diagnosis in each category was 22 of 31 (71%) for the genetic cholestasis group, 2 of 46 (4.3%) for the unknown with complications group, and 4 of 32 (12.5%) for the unknown without complications group. The grouping of the molecular diagnoses in the group with genetic cholestasis was as follows: 12 with Alagille syndrome, 5 with neonatal Dubin-Johnson syndrome, 5 with neonatal intrahepatic cholestasis caused by citrin deficiency, and 6 with progressive familial intrahepatic cholestasis or benign recurrent intrahepatic cholestasis with low gamma-glutamyl transpeptidase levels. Several clinical datasets, including age of onset, direct bilirubin, and aminotransferases, were significantly different between the disorders confirmed using molecular genetic diagnosis.Targeted NGS can be used for molecular genetic diagnosis in subjects with NIIC. Clinical diagnosis should be accordingly redefined in the view of molecular genetic findings.
Morota N.,National Medical Center for Children and Mothers |
Kubota M.,National Medical Center for Children and Mothers |
Nemoto A.,Yokohama City University |
Katayama Y.,Nihon University
No To Hattatsu | Year: 2014
Objective: Initial outcome of intrathecal baclofen (ITB) treatment in Japan is being reported on. Methods: Chronological change of the Ashworth scale and complications after surgery were analyzed. Data were obtained from 71 children with severe spasticity who had received ITB screening tests by the end of March 2012. Results: Pump implantations for ITB treatment were performed in 43 children out of 62 whose spasticity reduced after baclofen injection at the screening tests. Postoperative evaluations of ITB treatment were carried out within one year and, in some cases, more than 2 years after surgery. Complications related to baclofen were reported on 19 occasions in 12 children within one year of ITB pump implantation, and on 9 occasions in 4 children of the 21 who were followed for more than 2 years. Main complications were hypertonia of muscle, liver dysfunction, and low blood pressure. The frequency of complications was lower than that reported previously. There was no apparent evidence to indicate that complications developed more in children than in adults in this study. The postoperative values of Ashworth scale in the upper and lower extremities were reduced markedly when compared with preoperative levels, and the improvements were statistically significant (P<0.05). Conclusions: This is the first report of outcome of ITB for severely disabled children with spasticity in Japan. It was confirmed that ITB for children with severe spasticity is a safe and effective treatment.
Kaneko Y.,National Medical Center for Children and Mothers
Kyobu geka. The Japanese journal of thoracic surgery | Year: 2015
Total anomalous pulmonary venous connection (TAPVC) is one of the most typical congenital heart defects requiring emergent surgery soon after birth. Obstruction of the pulmonary venous drainage that can lead to profound cyanosis, respiratory failure and shock indicates emergent intervention. Prenatal diagnosis of TAPVC contributes to a smooth transition from delivery to surgery. However, prenatal ultrasound screening frequently fails to reveal isolated TAPVC. In neonates with isolated obstructive TAPVC, common pulmonary venous chamber-to-left atrial anastomosis is the intervention of choice except in patients with severe intraventricular hemorrhage, extremely low birth weight, or gestational age of 30 weeks or less. In neonates with right isomerism and functional single ventricle but severely obstructive TAPVC, prognosis after neonatal surgery is extremely poor. Catheter intervention to delay open heart surgery may be preferred in such neonates.
Morota N.,National Medical Center for Children and Mothers
Japanese Journal of Neurosurgery | Year: 2011
Neurosurgical long-term management of myelomeningocele(MMC) involves hydrocephalus, Chiari malformation type 2(CM2), and tethered spinal cord. The rate of hydrocepalus requiring a VP shunt is reported to be declining to about 60% in some series. Shunt insufficiency can develop in more than 90% of those with VP shunts and the life-long management of VP shunt is a mandate. CM2, once regarded as life-threatening when it becomes symptomatic in infancy, also causes chronic respiratory problem for 20-60% of adult patients with MMC. Tethered cord syndrome(TCS) after MMC repair requiring surgical release develops in about 20-30% of patient. TCS often becomes symptomatic from school age to adolescence and careful observation is necessary for those children with MMC. Currently, MMC is no longer a seriously disabling disease as more than half (60-70%) of all patients are expected to return to social activity with some limitation. Finally late deterioration of neurological function as patients survive longer should be considered during the long-term follow-up for MMC patients.
Kaneko Y.,National Medical Center for Children and Mothers
Kyobu geka. The Japanese journal of thoracic surgery | Year: 2012
Appropriate treatment strategy for congenital heart disease may be influenced by coexisting congenital anomalies of respiratory or digestive system. Typical congenital anomalies that coexist frequently with congenital heart diseases and have influence on treatment strategy of congenital heart disease include trecheoesophageal fistula, diaphragmatic hernia, and tracheal stenosis. In neonates with congenital heart disease and tracheoesophageal fistula (the fistula) should be immediately repaired after birth, followed by cardiac surgery to ameliorate heart failure or hypoxemia if feasible. In neonates with congenital heart disease and diaphragmatic hernia, diaphragmatic hernia repair is performed first unless heart disease is life threatening. In patients with congenital heart disease and tracheal stenosis, concomitant repair of heart disease and tracheal stenosis is a reasonable strategy in most patients. The treatment of patients with congenital heart disease and coexisting congenital anomalies of respiratory or digestive system remains challenging. We believe that properly organized management by multidiciplinary approach is essential for best achievable outcome.