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Yoshihide Nakamura

Publications and source records attributed to Yoshihide Nakamura.

11 recordsLinked to original sources
PubMed2007

Genotype-phenotype correlations of KCNJ2 mutations in Japanese patients with Andersen-Tawil syndrome.

Andersen-Tawil syndrome (ATS) is a rare inherited disorder characterized by periodic paralysis, mild dysmorphic features, and QT or QU prolongation with ventricular arrhythmias in electrocardiograms (ECGs). Mutations of KCNJ2, encoding the human inward rectifying potassium channel Kir 2.1, have been identified in patients with ATS. We aimed to clarify the genotype-phenotype correlations in ATS patients. We screened 23 clinically diagnosed ATS patients from 13 unrelated Japanese families. Ten different forms of KCNJ2 mutations were identified in the 23 ATS patients included in this study. Their ECGs showed normal QTc intervals and abnormal U waves with QUc prolongation and a variety of ventricular arrhythmias. Especially, bidirectional ventricular tachycardia (VT) was observed in 13 of 23 patients (57%). Periodic paralysis was seen in 13 of 23 carriers (57%), dysmorphic features in 17 (74%), and seizures during infancy in 4 (17%). Functional assays for the two novel KCNJ2 mutations (c. 200G>A (p. R67Q) and c. 436G>A (p. G146S)) displayed no functional inward rectifying currents in a heterologous expression system and showed strong dominant negative effects when co-expressed with wild-type KCNJ2 channels (91% and 84% reduction at -50 mV respectively compared to wild-type alone). Immunocytochemistry and confocal imaging revealed normal trafficking for mutant channels. In our study, all of the clinically diagnosed ATS patients had KCNJ2 mutations and showed a high penetrance with regard to the typical cardiac phenotypes: predominant U wave and ventricular arrhythmias, typically bidirectional VT.

Adolescent↗
PubMed2006

Standardization of 152Eu and 154Eu by 4pibeta-4pigamma coincidence method and 4pi(beta+gamma) integral counting.

The 4pibeta-4pigamma coincidence counting and 4pi(beta+gamma) integral counting techniques were applied for the standardization of 152Eu and 154Eu. In these techniques, the beta-detector is composed of two thin plastic scintillators sandwiching the source coupled with a slender photomultiplier tube. This beta-detector was inserted into a large well-type NaI(Tl) scintillation detector for gamma-ray detection, making a 4pibeta-4pigamma detector configuration. The results obtained by the above two techniques were in good agreement and consistent with the results of international comparisons.

Algorithms↗
PubMed2005

Phenotypes with GATA4 or NKX2.5 mutations in familial atrial septal defect.

Recently, GATA4 and NKX2.5 were reported as the disease genes of atrial septal defect (ASD) but the relationship between the locations of their mutations and phenotypes is not clear. We analyzed GATA4 and NKX2.5 mutations in 16 familial ASD cases, including four probands with atrioventricular conduction disturbance (AV block) and two with pulmonary stenosis (PS), by PCR and direct sequencing, and examined their phenotypes clinically. Five mutations, including two GATA4 and three NKX2.5 mutations, were identified in 31.3% of the probands with ASD, and three of them were novel. The two GATA4 mutations in the probands without AV block were S52F and E359Xfs (c.1075delG) that was reported previously, and three NKX2.5 mutations in the probands with AV block were A88Xfs (c.262delG), R190C, and T178M. Additionally, we observed some remarkable phenotypes, i.e., dextrocardia with E359Xfs (c.1075delG) and cribriform type ASD with R190C, both of which are expected to be clues for further investigations. Furthermore, progressive, most severe AV block was closely related with a missense mutation in a homeodomain or with a nonsense/frame-shift mutation of NKX2.5 for which classification has not been clearly proposed. This pinpoints essential sites of NKX2.5 in the development of the conduction system.

DNA↗
PubMed2005

Combined rotational osteotomy and vascularized iliac bone graft for advanced osteonecrosis of the femoral head.

This paper describes the rationale and technique for a combined procedure of transtrochanteric rotational osteotomy and vascularized iliac bone grafting in cases of osteonecrosis of the femoral head with an extensive and widely collapsed necrotic lesion in young patients. The authors performed this combined operation for 12 joints in 12 patients over 14 years from 1984 until 1997. At a mean of 81 months after the operation, in eight patients who had no pain, the average Harris hip score was 90.0 points. Postoperative radiographic evaluation revealed that collapse (more than 2 mm) of the femoral head was prevented in ten patients. Conversion to an endoprosthesis was avoided in all patients except one in this series. The authors recommend this procedure for advanced and extensive osteonecrosis of the femoral head, especially in young patients, to preserve the joint, even though it is a relatively complex procedure.

Adolescent↗
PubMed2004

Spontaneous closure of ventricular septal defects followed up from <3 months of age.

BACKGROUND: This study evaluates the incidence and timing of spontaneous closure (SC) of ventricular septal defect (VSD) using Doppler color flow mapping. METHODS: A total of 225 infants (mean age 30 days) were diagnosed with uncomplicated VSD: 31 (14%) subpulmonary VSD, 159 (70%) perimembranous, and 35 (16%) muscular. The patients were divided into two groups according to the presence or absence of congestive heart failure (CHF). SC was confirmed with color Doppler. RESULTS: Surgical closure was performed in 59 patients (26%). SC occurred in 107 patients (48%); three (10%) of 31 with subpulmonary VSD, 75 (47%) of 159 with perimembranous VSD, and 29 (83%) of 35 with a muscular VSD. Average age at SC was 19 months. In three SC patients with a subpulmonary VSD, there was no aortic valve prolapse and no aortic regurgitation. SC occurred in 96% of SC patients with a perimembranous VSD by the age of 6 years, and in 93% of those with a muscular VSD by the age of 3 years. In patients without CHF, the rate of SC was 72%; 23% in subpulmonary VSD, 74% in perimembranous, and 85% in muscular. SC occurred in only 23% of patients with a perimembranous VSD with CHF. Mean age at the final examination was 6.9 years in 59 patients with a VSD remaining open, and 63% of patients with a perimembranous VSD remaining open had an aneurysm of the ventricular membranous septum. CONCLUSIONS: The SC rate of VSD by mean age of 6.9 years was 48%, but it was 72% in patients without CHF. In patients with CHF, SC was seen only in patients with a perimembranous VSD. The rate of SC was 10% in subpulmonary VSD. The authors contend that SC probably occurred by growth of muscular septum surrounding VSD. Muscular VSD spontaneously closed earlier than perimembranous VSD.

Echocardiography, Doppler, Color↗
PubMed2004

Additional gene variants reduce effectiveness of beta-blockers in the LQT1 form of long QT syndrome.

INTRODUCTION: Beta-blockers are widely used to prevent the lethal cardiac events associated with the long QT syndrome (LQTS), especially in KCNQ1-related LQTS (LQT1) patients. Some LQT1 patients, however, are refractory to this therapy. METHODS AND RESULTS: Eighteen symptomatic LQTS patients (12 families) were genetically diagnosed as having heterozygous KCNQ1 variants and received beta-blocker therapy. Cardiac events recurred in 4 members (3 families) despite continued therapy during mean follow-up of 70 months. Three of these patients (2 families) had the same mutation [A341V (KCNQ1)]; and the other had R243H (KCNQ1). The latter patient took aprindine, which seemed to be responsible for the event. By functional assay using a heterologous mammalian expression system, we found that A341V (KCNQ1) is a loss-of-function type mutation (not dominant negative). Further genetic screening revealed that one A341V (KCNQ1) family cosegregated with S706C (KCNH2) and another with G144S (KCNJ2). Functional assay of the S706C (KCNH2) mutation was found to reduce the current density of expressed heterozygous KCNH2 channels with a positive shift (+8 mV) of the activation curve. Action potential simulation study was conducted based on the KYOTO model to estimate the influence of additional gene modifiers. In both models mimicking LQT1 plus 2 and LQT1 plus 7, the incidence of early afterdepolarization was increased compared with the LQT1 model under the setting of beta-adrenergic stimulation. CONCLUSION: Multiple mutations in different LQTS-related genes may modify clinical characteristics. Expanded gene survey may be required in LQT1 patients who are resistant to beta-blocker therapy.

Action Potentials↗
PubMed2004

Arrhythmias late after repair of tetralogy of fallot: a Japanese Multicenter Study.

BACKGROUND: Arrhythmia is a major late complication in adults with repaired tetralogy of Fallot, although a large-scale study has not been carried out in Japan. METHODS AND RESULTS: A nationwide multicenter study with 512 operative survivors was performed. Actuarial survival rate at 30 years (maximum follow-up) was 98.4%. Fifty-four patients (10.5%) had clinically important arrhythmias, including 23 patients with bradycardia caused by sick sinus syndrome or atrioventricular block (AVB). A patient with complete AVB (CAVB) without pacemaker implantation (PMI) died later. Two patients had sustained ventricular tachycardia (VT) and syncope was reported in 18 patients with ventricular arrhythmias (VA). Atrial tachyarrhythmias were observed in 13 patients. Older age at operation was a risk factor for atrial fibrillation/flutter, longer postoperative survival duration for VA, and QRS duration >120 ms for VT. Perimembranous ventricular septal defect was related to CAVB. Right ventricular outflow patch was not a risk factor. Importantly, 60% of the subjects had QRS duration <120 ms. CONCLUSION: The prevalence of serious arrhythmias is low in Japanese TOF patients as compared with the results from Western countries. CAVB without PMI and VT are the major risk factors for late morbidity and mortality. The excellent result could be related to the narrow QRS after surgery.

Adolescent↗
PubMed2003

Catheter ablation for a right anteroseptal accessory pathway in a patient with an endocardial cushion defect.

We report a radiofrequency catheter ablation for atrioventricular reentrant tachycardia in a patient with a right anteroseptal accessory pathway complicating an endocardial cushion defect. His bundle potential was recorded 20 mm posterior to the accessory pathway. In the presence of associated congenital heart disease, it is very important to understand the anatomy of the conduction system prior to radiofrequency catheter ablation.

Adolescent↗
PubMed2002

Synthesis and antitumor activity of novel pyrimidinyl pyrazole derivatives. II. Optimization of the phenylpiperazine moiety of 1-[5-methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-3-phenylpiperazinyl-1-trans-propenes.

A series of novel 3-substituted-1-[5-methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-1-trans-propenes in order to improve the in vitro and in vivo activity of our prototype 3-[4-(3-chlorophenyl)-1-piperazinyl]-1-[5-methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-1-trans-propene (2) were synthesized and evaluated by assays of growth inhibition against several tumor cell lines in vitro and antitumor activity against some tumor models when dosed both intraperitoneally and orally in vivo. Compounds 7a and 7e, the 3,5-difluorophenyl and 3,5-dichlorophenyl analogues of 2, respectively, showed significantly more potent cytotoxicity than 2 in vitro and potent antitumor activities without causing decrease of body temperature related to side effects.

Animals↗
PubMedDate not supplied

Myocardial ischemia in Kawasaki disease: evaluation with dipyridamole stress technetium 99m tetrofosmin scintigraphy.

BACKGROUND: The coronary artery abnormalities in Kawasaki disease (KD) often cause myocardial ischemia. Previous publications have described the use of thallium 201 myocardial perfusion imaging to determine the extent of ischemia in patients with KD. The technetium perfusion agents offer better resolution and may offer additional information about ventricular function in these patients. This study was performed to evaluate myocardial perfusion in patients with KD through use of technetium 99m tetrofosmin (TF) in conjunction with dipyridamole vasodilator stress. METHODS AND RESULTS: Eighty-six patients with KD aged 11.5 +/- 6.4 years and 20 age-matched control patients without heart disease were studied. Among 86 patients with KD, significant coronary artery stenosis (>or=75%) was observed in 20, coronary aneurysm without stenosis in 37, and no coronary lesions in 29. After administration of high-dose dipyridamole infusion (0.70 mg/kg), 74 to 370 MBq TF was injected and 148 to 740 MBq TF was injected at rest 4 hours later. Single photon emission computed tomography images were obtained more than 30 minutes after TF injection. Regional myocardial hypoperfusion was observed in 18 patients who had coronary artery stenosis of 75% or greater (sensitivity, 90%, and specificity, 100%). Two patients did not demonstrate ischemic changes in coronary artery stenosis in group I; one had good collateral flow. There were no TF injection-related complications. CONCLUSIONS: Tetrofosmin myocardial perfusion imaging can detect regional hypoperfusion in children with KD.

Adolescent↗