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Biomedical subjects

Hiroshi Kasanuki

Publications and source records attributed to Hiroshi Kasanuki.

At least 19 recordsLinked to original sources
PubMed2003

Specific regulation of nucleocytoplasmic distribution of poly(C)-binding protein gene mRNA in mouse development.

Post-transcriptional regulation plays a pivotal role in gene expression. In this study, the intracellular distribution of the murine cytoplasmic poly(C)-binding protein (alphaCP2) gene transcript was investigated. The nucleocytoplasmic mRNA distribution of alphaCP2 was shown to change throughout the course of mouse development. Furthermore, in situ hybridization of the embryo revealed that the alphaCP2 transcript was widely distributed in the cytoplasm of endothelial cells and cardiac myocytes, but accumulated in the nuclei of other cells. In the adult, alphaCP2 was ubiquitously expressed and alphaCP2 mRNA was found to accumulate in the nucleus. In vitro experiments showed that the nucleocytoplasmic mRNA distribution of alphaCP2 mRNA was distinct from that of the GAPDH gene used as an internal control. These results suggest that the intracellular distribution of alphaCP2 mRNA is developmentally regulated in a gene and/or cell specific manner.

Aging↗
PubMed2003

Oxidized LDL receptor gene (OLR1) is associated with the risk of myocardial infarction.

Lectin-like oxidized low-density lipoprotein receptor (LOX-1/OLR1) has been suggested to play a role in the progression of atherogenesis. We analyzed the OLR1 gene and found a single nucleotide polymorphism (SNP), G501C, in patients with ischemic heart disease from a single family, which resulted in the missense mutation of K167N in LOX-1 protein. We compared the group of patients with myocardial infarction (MI) (n=102) with a group of clinically healthy subjects (n=102), and found that the MI group had a significantly high frequency of 501G/C+501C/C (38.2%) compared with the healthy group (17.6%; p<0.002). The odds ratio for the risk of MI associated with the 501G/C+501C/C genotype was 2.89 (95% CI, 1.51-5.53). These findings suggest that OLR1 or a neighboring gene linked with G501C SNP is important for the incidence of MI. Manipulating LOX-1 activity might be a useful therapeutic and preventative approach for coronary artery disease, especially for individuals with the G501C genotype of OLR1.

Case-Control Studies↗
PubMed2003

FGF-1 enhanced cardiogenesis in differentiating embryonal carcinoma cell cultures, which was opposite to the effect of FGF-2.

To investigate the effect of fibroblast growth factors (FGFs) on cellular differentiation, we employed a multipotent mouse embryonal carcinoma cell line, P19, which differentiates into cardiac muscle, skeletal muscle and neural cells in the presence of the appropriate concentrations of retinoic acid (RA). Under conditions appropriate for cardiac muscle differentiation, the expression of FGF-1 was significantly enhanced before any tissue-specific gene was induced. In contrast, up-regulation of the FGF-2 gene was observed with skeletal muscle-inducing concentrations of RA. Exogenous FGF-1, under skeletal muscle-inducing conditions, suppressed the expression of marker genes for skeletal muscle and induced cardiac alpha myosin heavy chain (alphaMHC) gene with up-regulation of bone morphogenetic protein-4 (BMP-4) and GATA-4. Unlike FGF-1, exogenous FGF-2 promoted skeletal muscle differentiation. These results indicate that FGF-1 and FGF-2 play different roles in P19 cell differentiation induced by RA.

Animals↗
PubMed2003

Angiographic findings and surgical treatments of coronary artery involvement in Takayasu arteritis.

BACKGROUND: Takayasu arteritis is associated with a low incidence of coronary artery involvement, such as stenosis, obstruction, aneurysm, and coronary steal syndrome, but coronary ischemia can be fatal. METHODS: Between 1972 and April 2001, 81 of 130 patients given a diagnosis of Takayasu arteritis underwent selective coronary angiography, and among them, 31 patients (4 male and 27 female patients; mean age, 41.1 +/- 13.2 years) had abnormal coronary angiographic findings and were recruited for this study. RESULTS: Abnormal coronary findings consisted of 24 coronary artery stenoses of greater than 75%, 3 coronary artery-bronchial artery anastomoses, 3 aneurysmal coronary ectasias, and 1 combined coronary ectasia and anastomosis. Among 24 patients with coronary stenosis, the ostium was most frequently involved (87.5%). Twenty-three of 24 patients with coronary artery stenoses were treated surgically. The mean follow-up duration was 9.65 +/- 6.9 years, with a 100% follow-up rate. Four fistulas and 4 aneurysms in 7 patients were not treated surgically. Coronary steal phenomenon was always associated with occluded pulmonary arteries and pulmonary hypertension. Aneurysmal coronary ectasia was related to severe aortic hypertension with or without aortic regurgitation and atypical coarctation. There were 2 (8.7%) in-hospital deaths and 3 (13%) late deaths. The actuarial survival rate, including in-hospital deaths, was 86.5% +/- 7.3% at 5 years and 81.4% +/- 8.4% at 10 years. CONCLUSION: The incidence of coronary abnormalities is relatively low in patients with Takayasu arteritis; however, surgical treatment is recommended for patients with coronary ostial stenoses because coronary ischemia can be one of the major causes of death.

Actuarial Analysis↗
PubMed2003

Clinical significance of prolonged P wave width after right atrial appendage pacing in sick sinus syndrome.

The present study investigated both the clinical significance of atrial fibrillation (AF) before right atrial appendage (RAA) pacing and the influence of prolonged P wave on AF occurrence in RAA-paced patients with sick sinus syndrome (SSS). Fifty-seven patients (age 68+/-10 years; 19 men, 38 women) with SSS who underwent RAA pacing were divided into 2 groups: 23 patients without AF before pacing (I + II; Rubenstein I or II) and 34 patients with AF before pacing (III; Rubenstein III). The P wave duration in intrinsic rhythm and with RAA pacing were measured on the standard electrocardiography in leads II and V(1) with the use of a digitizing tablet. Group III was further subdivided into 2 groups: 20 patients (IIIb) with a paced P wave >130 ms in both leads II and V(1) and the other 14 patients (IIIa). The duration of the intrinsic P wave in leads II and V(1) was significantly greater in group III than in group I + II (119+/-20 vs 108+/-21 ms, p=0.0417, 106+/-16 vs 95+/-21 ms, p=0.0258, respectively). During the follow-up of 40+/-21 months, AF recurrence was significantly higher in group IIIb than in groups IIIa and I + II (17/20 vs 5/14 vs 2/23 p<0.0001). A few occurrences of AF were observed by conventional RAA pacing in patients without AF before pacing. However, SSS with AF before pacing caused a significant intra-atrial conduction disturbance and a high incidence of AF recurrence after implantation of RAA pacing, especially in patients with a prolonged paced P wave, in whom new pacing modalities may be needed to shorten paced P wave duration and prevent AF.

Aged↗
PubMed2003

Cardiac muscle cell disorganization in apical hypertrophic cardiomyopathy: a cardiac biopsy study.

Apical hypertrophic cardiomyopathy has been divided into two entities: apical asymmetric septal hypertrophy (apical ASH) and apical symmetric hypertrophy (AH). The latter differs clinically from hypertrophic cardiomyopathy (HCM) with ASH, and it is unclear whether AH represents a distinct subtype of HCM. In the present study, the presence or absence and the extent of cardiac muscle cell disorganization, a histologic characteristic of HCM, were compared in patients with AH (n = 10) and ASH (n = 29) in whom cardiac biopsy specimens were obtained from the left ventricular apex and interventricular septum. Disorganization was graded as (1+) in only 1 patient in the AH group and (-) in the remaining 9. In contrast, in the ASH group disorganization was graded as (1+) in 15 patients, (2+) in 7, (3+) in 3, and (-) in only 4 (P < 0.0001). Thus, it was observed that in AH disorganization is virtually absent or at most limited to a very narrow area. It is concluded from a histological stand point as well that the type of apical hypertrophic cardiomyopathy showing apical symmetric hypertrophy differs from usual HCM.

Biopsy↗
PubMed2003

Hemodynamics during chronic amiodarone administration in Japanese patients with idiopathic dilated cardiomyopathy and ventricular arrhythmia: a retrospective study.

OBJECTIVES: Nonischemic heart disease, especially idiopathic dilated cardiomyopathy, is relatively common among Japanese patients receiving amiodarone for concomitant ventricular arrhythmia, but the hemodynamic effects of amiodarone in these Japanese patients are unclear. The hemodynamic changes during chronic amiodarone administration were retrospectively studied in patients with idiopathic dilated cardiomyopathy and ventricular arrhythmia. METHODS: Fifty-two patients [42 males, 10 females, 53 +/- 2 years (mean age +/- SE)] with ventricular tachyarrhythmia and idiopathic dilated cardiomyopathy with left ventricular ejection fraction of 27 +/- 1% (mean +/- SE) were treated with 200-400 mg daily of oral amiodarone as the loading dose for the initial 14 days and 100-200 mg daily maintenance dose for a further 6 months. No patients were taking beta-blockers or positive inotropic drugs. Echocardiographic examination was performed before (baseline), at week 2 and at month 6 of amiodarone therapy. Twenty four-hour Holter monitoring during the same time period was also performed in 34 patients. Seventeen patients underwent right heart catheterization before and at week 2. RESULTS: Echocardiographic measurements showed no significant change in left ventricular end-diastolic dimension, although there was a slight increase in fractional shortening from 16 +/- 1% to 19 +/- 1% (p < 0.05) and 18 +/- 1% (mean +/- SE) (p < 0.01) at week 2 and month 6 of amiodarone therapy, respectively. Amiodarone markedly reduced the mean heart rate and the frequency of premature ventricular complexes on ambulatory monitoring. The cardiac index did not change and the pulmonary capillary wedge pressure tended to decrease slightly at week 2 in the 17 patients who underwent catheterization. CONCLUSIONS: This retrospective study showed no worsening of the hemodynamic state during chronic amiodarone administration in Japanese patients with idiopathic dilated cardiomyopathy and ventricular arrhythmia.

Adult↗
PubMed2003

[Clinical significance of early percutaneous coronary intervention in patients with Braunwald III-B type unstable angina pectoris].

OBJECTIVES: To assess the efficacy of early invasive strategy for the treatment of Braunwald III-B type unstable angina pectoris. METHODS: This study included 573 consecutive patients of whom 267 underwent percutaneous coronary intervention (PCI) (312 lesions). The patients were divided into two groups, 95 treated with the early invasive strategy of coronary angiography within 24 hr of admission (Group PCI-I) and the remaining 172 treated with the early conservative strategy of coronary angiography 24 hr after admission (Group PCI-C). RESULTS: No significant differences were noted in the baseline characteristics of the two groups except for ST segment elevation on electrocardiography at presentation, which occurred significantly less frequently in Group PCI-C (36.8% vs 8.1%, p < 0.0001). The initial success rate of percutaneous coronary intervention was sufficiently high in both groups (Group PCI-I: 96.9% vs Group PCI-C: 97.7%, NS). Acute myocardial infarction occurred in six patients of Group PCI-C (3.5%) because of the side branch occlusion. There was no in-hospital death or emergent coronary artery bypass grafting. During the 6-month follow-up, there were no significant differences in the death rates (2.1% vs 1.7%), the death or myocardial infarction rates (5.3% vs 5.8%) and the target lesion revascularization ratio (26.0% vs 25.7%) between Group PCI-I and Group PCI-C. CONCLUSIONS: The clinical outcomes of the early invasive strategy for unstable angina pectoris were almost equivalent to those of the early conservative strategy, despite more frequent ST segmental elevation at admission in Group PCI-I. These findings suggest that the early invasive strategy for unstable angina pectoris may be acceptable even in the current Japanese clinical setting without the use of GP IIb/IIIa receptor antagonist, low molecular weight heparin or clopidogrel.

Adult↗
PubMed2002

Expression of peroxisome proliferator-activated receptor-gamma in vascular smooth muscle cells is upregulated in cystic medial degeneration of annuloaortic ectasia in Marfan syndrome.

BACKGROUND: Cystic medial degeneration (CMD) is a histological abnormality that is common in annuloaortic ectasia (AAE) and aortic dissection with Marfan syndrome. Apoptosis and loss of vascular smooth muscle cells (VSMCs) is one of the features of CMD, but little is known about its pathogenesis. Peroxisome proliferator-activated receptor-gamma (PPARgamma), a transcription factor of the nuclear receptor superfamily, has been reported to show antiproliferative effects on VSMCs as well as anti-inflammatory effects on macrophages. PPARgamma agonist has been recently reported to induce apoptosis of cultured VSMCs. METHODS: We examined the histopathology of ascending aortas in AAE of Marfan patients (n=21) and control patients (n=6) at surgery. RT-PCR was performed to demonstrate expression of PPARgamma in CMD. Localization of PPARgamma was determined by double immunostaining using antibodies against PPARgamma and cell-specific markers (ie, SMCs, macrophages, and T lymphocytes). RESULTS: PPARgamma expression was upregulated in AAE samples but minimal in control samples by RT-PCR (P=0.07). Immunoreactivity against PPARgamma in numerous nuclei of VSMCs was observed in CMD lesions. Severity of CMD correlated with positive immunoreactivity of PPARgamma in medial VSMCs (P=0.03). No inflammatory cells (ie, macrophages or T lymphocytes) were detected in CMD lesions. CONCLUSION: PPARgamma expression is upregulated in SMCs of CMD without any inflammatory response. Activated PPARgamma in VSMCs might be involved in the pathogenesis of CMD in Marfan's aortas. Regulation of PPARgamma might lead to clinical implication in protection against progression of AAE.

Adult↗
PubMed2002

Levosimendan increases L-type Ca(2+) current via phosphodiesterase-3 inhibition in human cardiac myocytes.

To evaluate the potency of levosimendan, a newly developed cardiotonic agent, as a phosphodiesterase-3 inhibitor, we examined its effects on the L-type Ca(2+) current (I(Ca,L)) in single human atrial cells using the whole-cell voltage-clamp method. Levosimendan significantly increased I(Ca,L) in a concentration-dependent manner (E(max), 139.0 +/- 1.8%; EC(50), 54 +/- 3.6 nM). The increase in I(Ca,L) induced by 1 microM levosimendan was significantly greater in human atrial cells (136.7 +/- 11.0%, n=8) than in rabbit atrial cells (23.5 +/- 3.5%, n=6) (depolarization to +10 mV in each case). In rat atrial and ventricular cells, I(Ca,L) was unaffected by 1-10 microM levosimendan. These results indicate that the selective phosphodiesterase-3 inhibitor levosimendan increases cardiac-cell I(Ca,L) significantly more strongly in human than in rabbit and rat. It seems likely that the positive inotropic effect of levosimendan on the human myocardium depends on an increase in I(Ca,L) that is modulated by adenosine 3'5'-cyclic monophosphate (cAMP)-dependent phosphorylation.

1-Methyl-3-isobutylxanthine↗
PubMed2002

Amiodarone distribution in human tissues after long-term therapy: a case of arrhythmogenic right ventricular cardiomyopathy.

The tissue distribution of amiodarone and desethylamiodarone, its active metabolite, was examined in an autopsied case, an 85-year-old man, with arrhythmogenic right ventricular cardiomyopathy (ARVC) who had been receiving amiodarone for 4 years. High concentrations of amiodarone, a very highly lipophilic compound, were found in adipose and bone marrow tissues. Despite a low dose (100 mg daily), the concentrations of amiodarone were higher in the epicardial fat (570.4 microg/g) and in the right atrium (165.3 microg/g) than previously reported in patients with other cardiac diseases. The ratios of amiodarone/ desethylamiodarone concentrations in both tissues were >1. This unique distribution demonstrates the involvement of histological characteristics of ARVC, such as fatty replacement of myocardium. We anticipate that a low dose of amiodarone would be effective in preventing arrhythmia in some patients with ARVC.

Adipose Tissue↗
PubMed2002

Subepicardial aneurysm after anticoagulant therapy for a mural thrombus following anterior myocardial infarction.

A subepicardial aneurysm became evident in a male patient after anticoagulant therapy. On admission, it appeared to be an old anterior infarction accompanied by a mural thrombus. After warfarin administration, the thrombus disappeared and an echo-free space emerged outside the apical myocardial wall. The echo-free space communicated with the left ventricular cavity through the apical myocardial wall. Emergency surgery was undertaken and the patient survived. The aneurysm was covered with epicardium and there was an endomyocardial rupture of the muscle in the apical wall, which was the entrance of the aneurysm. This case suggests that cautious follow-up with echocardiography is necessary when anticoagulant therapy is selected for thrombi following myocardial infarction.

Anticoagulants↗