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Biomedical subjects

Yoko Hagiwara

Publications and source records attributed to Yoko Hagiwara.

7 recordsLinked to original sources
PubMed2005

Link between SCN5A mutation and the Brugada syndrome ECG phenotype: simulation study.

BACKGROUND: The specific changes in the gating kinetics of the sodium current (I(Na)) responsible for its phenotype have remained to be elucidated. In the present study the effect of changes in the gating kinetics of I(Na) on early repolarization (ER) and initiation of phase 2 reentry (P2R) were evaluated in a theoretical epicardial ventricular fiber model. METHODS AND RESULTS: Miyoshi-I(CaL) was incorporated into the modified Luo-Rudy dynamic (LRd) model. Dispersion at Ito-density was set within a theoretical fiber composed of serially arranged epicardial cells with gap junctions. The following changes in I(Na) kinetics were made: (1) a-10 mV shift in steady-state inactivation, (2) a+10 mV shift in steady-state activation curve, (3) a small inactivation time constant (DEC); P2R and ER were observed. A conduction disturbance within the fiber was simulated and only when the I(Na)-density was decreased did DEC, especially, show a marked increase in the likelihood of causing ER and P2R. Conduction disturbance significantly increased the likelihood causing ER or P2R. CONCLUSIONS: In this one-dimension model with Ito-density dispersion, DEC-I(Na) precipitates I(Na)-blocker inducible ER. This suggests that the characteristic ST-segment elevation in the Brugada syndrome with SCN5A mutation can be interpreted in part by DEC-I(Na). Concomitant conduction disturbance may be required to cause P2R at physiological Ito density.

Arrhythmias, Cardiac↗
PubMed2004

Autoimmunity against the second extracellular loop of beta(1)-adrenergic receptors induces early afterdepolarization and decreases in K-channel density in rabbits.

OBJECTIVES: We sought to define the electrophysiologic property of the rabbit heart associated with autoimmunity against the second extracellular loop of the beta(1)-adrenergic receptor. BACKGROUND: Sudden death of patients with cardiomyopathy, probably due to lethal ventricular arrhythmias, can be predicted by the presence of autoantibodies against the second extracellular loop of the beta(1)-adrenergic receptor. METHODS: Rabbits were immunized by repetitive subcutaneous administration of a synthetic peptide corresponding to the second extracellular loop of beta(1)-adrenergic receptors (beta group; n = 30) for a mean of 4.2 months. Control rabbits received only vehicle (control group; n = 30). RESULTS: One of the rabbits in the beta group died suddenly during the observation period, but none of the control animals died. The prevalence of sustained ventricular tachycardia was significantly higher in the beta group (beta: 4 of 27 vs. control: 0 of 30), and a standard microelectrode experiment revealed prolongation of the action potential duration (APD) in the right ventricular papillary muscle (beta: 156 +/- 5 ms vs. control: 131 +/- 4 ms; p < 0.05). Early afterdepolarization (EAD) was observed in one rabbit in the beta group (1 of 26), but not in any animals in the control group (0 of 17). A dose of 100 nmol/l of E-4031 induced EAD in the beta group (10 of 10), but not in the control group, except for one rabbit (1 of 10). The whole-cell, patch-clamp experiment on left ventricular M cells showed significant decreases in transient outward current (I(to1)) (-43%) and slowly activated delayed rectifier current (I(Ks)) densities (-33%), whereas the inward-rectifying K current (I(K1)) and rapidly activated delayed rectifier current (I(Kr)) densities remained unchanged. CONCLUSIONS: Long-term immunization against the second extracellular loop of the beta(1)-adrenergic receptor caused EAD and APD prolongation and decreased the K-channel density, suggesting that an arrhythmic substrate via autoimmune mechanisms is present in cardiomyopathic patients who have autoantibodies directed against the receptors.

Action Potentials↗
PubMed2004

Multiple primary cancers in patients with osteosarcoma: influence of anticancer drugs and genetic factors.

One hundred thirty-five patients younger than 30 years with osteosarcoma were treated at the Chiba Cancer Center between 1976 and 1999. They included six patients with second cancer after cure of osteosarcoma (group A) and three patients with osteosarcoma as second cancer after cure of childhood cancers (group B). Third cancer occurred in one patient of group A. The clinical features of these nine patients were studied. The diagnoses of second cancer in group A consisted of two acute myelogenous leukemias, two breast carcinomas, one malignant phyllodes tumor of breast, and one ovarian carcinoma. The third cancer was uterine leiomyosarcoma. Second cancer occurred an average of 7.2 years after occurrence of osteosarcoma. The diagnoses of first cancer in group B consisted of one adrenocortical carcinoma, one malignant teratoma of sacrum, and one ovarian carcinoma (yolk sac tumor). Osteosarcoma occurred on average 12.7 years after occurrence of first cancer. Two patients had germ-line p53 gene mutation. Anticancer drugs and genetic factors are presumed to be concerned with occurrence of second cancer. The frequency of multiple primary cancers in patients with osteosarcoma is by no means low. Strict follow-up is thus needed over a long period.

Adolescent↗
PubMed2003

Marriage and fertility in long-term survivors of high grade osteosarcoma.

One hundred fifteen patients with high grade osteosarcoma were treated at our hospital between 1976 and 1995. Of these, 45 patients still surviving and disease free for more than 5 years since the conclusion of treatment were enrolled as the subjects. The marriage proportion (number of married persons/number of all persons) and fertility proportion (number of persons having an offspring/number of married persons) of these 45 patients were investigated. The marriage proportion of male patients was 20.8% (5/24), whereas that of female patients was 76.2% (16/21). The marriage proportion in male patients was dramatically lower than that in female patients (p = 0.0003). The marriage proportion in male patients was significantly lower than that in brothers of the patients (p = 0.0223). In female patients, the treatment of osteosarcoma had no influence on marriage, whereas in male patients it had a great influence on marriage. The fertility proportion in married patients was 76.2% (16/21) and that in siblings of the patients was 81.0% (17/21). A total of 18 offspring were born to married patients. These offspring had no birth defects or congenital anomalies. The chemotherapy used in the treatment of osteosarcoma had little influence on the fertility of patients or the health of their offspring.

Adult↗
PubMed2002

A mathematical model of phase 2 reentry: role of L-type Ca current.

Phase 2 reentry (P2R) is known to be one of the mechanisms of malignant ventricular arrhythmias, especially those associated with Brugada syndrome. However, little is known about the underlying mechanism for P2R. Our aim in this study was to simulate P2R in a mathematical model to enable us to understand its mechanism and identify a potential therapeutic target. A mathematical model of the L-type Ca current was composed according to whole cell current data from guinea pig ventricular myocytes recorded at 37 degrees C. Our mathematical model was incorporated into the modified Luo-Rudy phase 2 model. We set a dispersion in transient outward current (I(to)) density within the theoretical fiber, composed of 80 serially arranged epicardial cells with gap junctions and then observed the P2R. The dispersion in I(to) density within an only 0.8-cm epicardial theoretical fiber generated P2R with our Ca channel but not with the original model. When the P2R developed in the theoretical fiber, the calculated extracellular field potential showed coved-type ST segment elevation. We succeeded in generating P2R in our model for the first time. The local epicardial P2R may contribute the genesis of coved-type ST segment elevation in the Brugada syndrome.

Action Potentials↗
PubMed2002

[Guidelines for antiarrhythmic therapy].

Recentry, therapies for arrhythmias have been extremely advanced by accumulation of electrophysiological knowledge, improvement of diagnostic technique, and development of antiarrhythmic drugs and devices(pacemakers, catheter ablation and implantable cardioverter-defibrillators). After the report of the CAST(Cardiac Arrhythmia Suppression Trial), the Sicilian Gambit was presented as new strategies of drug therapy. Now in the United States, three AHA guidelines were published. Besides in Japan 'the guidelines for antiarrhythmic drugs' based on the Sicilian Gambit was published. 'The guidelines for management of Atrial fibrillation' and 'the guidelines for antiarrhythmic devices' were also reported. Here, these guidelines are reviewed.

Anti-Arrhythmia Agents↗