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Biomedical subjects

K Fujino

Publications and source records attributed to K Fujino.

At least 19 recordsLinked to original sources

Endothelin blocks ATP-sensitive K+ channels and depolarizes smooth muscle cells of porcine coronary artery.

ATP-sensitive K+ channels with a conductance of 30 pS in smooth muscle cells of porcine coronary artery were found to be highly active in the intact cell-attached patch configuration when the pipette contained a physiological concentration of Ca2+ (greater than 10(-4) M). In the inside-out configuration, these channels were activated by extracellular Ca2+ and blocked by cytosolic ATP and glibenclamide. Endothelin applied to the pipette specifically blocked these channels in a concentration-dependent manner in the cell-attached configuration (half-maximal inhibition, 1.3 x 10(-9) M). A K+ channel opener, nicorandil, activated these channels even in the presence of 10(-8) M endothelin. In the whole-cell current-clamp method, the cell membrane was depolarized by endothelin and then repolarized by nicorandil. The membrane depolarization is closely related to contraction of smooth muscle cells. These results suggest that the ATP-sensitive K+ channels are important in controlling the vascular tone of the coronary artery and that endothelin can increase vascular tone by blocking these channels.

Adenosine Triphosphate

Paraganglioma associated with hypoglycemia.

A 63-year-old female had frequent attacks of palpitations with sweating and occasional loss of consciousness for 7 years before admission. These symptoms and documented hypoglycemia (blood glucose: 46 mg/dl) suggested insulinoma, but computed tomography demonstrated a retroperitoneal tumor which was diagnosed as a paraganglioma by histological examination of the resected specimen.

Adrenal Glands

Electrophysiological actions of the pimobendan metabolite, UD-CG 212 Cl, in guinea pig myocardium.

Pimobendan (UD-CG 115 BS), an inotropic agent and inhibitor of type III phosphodiesterase activity, is demethylated in vivo to form UD-CG 212 Cl, which is a more potent type III phosphodiesterase inhibitor. This study examined cyclic AMP (cAMP)-mediated actions of UD-CG 212 Cl. In guinea pig papillary muscles, UD-CG 212 Cl increased cAMP and stimulated Ca(++)-dependent slow action potentials (APs) in a dose-dependent manner. When compared to previous studies using pimobendan, UD-CG 212 Cl was approximately 100-fold more potent. UD-CG 212 Cl had no additional effects on slow APs in the presence of a maximal dose of isoproterenol (1 microM). Propranolol had little effect on UD-CG 212 Cl-induced slow APs. These results, along with previous studies, indicate that slow AP induction by UD-CG 212 Cl was cAMP-dependent, and the increase in cAMP levels was most likely due to phosphodiesterase inhibition and not beta receptor stimulation. Experiments with tetraethylammonium.Cl suggested that UD-CG 212 Cl probably did not induce slow APs by blocking K+ channels. In voltage-clamped ventricular myocytes UD-CG 212 Cl (100 microM) could stimulate Ca++ current (+21 +/- 5%) when basal cAMP levels were enhanced with a submaximal dose of isoproterenol (10(-9)-10(-8) M). Isoproterenol was not required to observe the stimulating effect of UD-CG 212 Cl on Ca++ current in intact, nondialyzed cells prepared using the nystatin-perforated patch method. Studies with the stereoisomers of UD-CG 212 Cl showed that the D-isomer was more potent than the L-isomer.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials

[Development of automated lactate analyzer with continuous blood sampling for monitoring blood lactate and its application for the testing of physical exercise].

The anaerobic threshold is useful for estimating the intensity of physical exercise. It is shown as either an increase in blood concentrations of lactate or a disproportionate increase in ventilation. We developed a lactate analyzer based on an electroenzymatic method with a continuous blood sampling system through a double-lumen catheter. Ascorbic acid, bilirubin, hemoglobin, creatinine, uric acid, and glucose did not interfere the results. The lactate concentrations in blood samples from healthy subjects during physical exercise correlated well (r = 0.993) with results measured by the conventional enzymatic method. We measured the concentrations of blood lactate with a use of this lactate analyzer to see the anaerobic threshold in nine healthy volunteers during exercise on a treadmill with an increasing workload. The point at which lactate concentrations started to increase was detected easily. The anaerobic threshold identified as a disproportionate increase in ventilation was seen at almost the same time. We conclude that the lactate analyzer, with a continuous blood sampling system, can measure precisely concentrations of lactate in blood and can detect the anaerobic threshold during physical exercise.

Adult

Apparent response of subacute sclerosing panencephalitis to intrathecal interferon alpha.

An 8-year-old boy with subacute sclerosing panencephalitis (SSPE) was treated with 1.0 to 3.0 x 10(6) IU human interferon alpha (IFN) by the intrathecal route weekly or fortnightly. Pronounced improvement of clinical and electroencephalographic findings were observed in a dose-dependent manner. Our patient raises hope that IFN can induce sustained remission in patients with SSPE.

Child

Phosphoramidon-sensitive endothelin converting enzyme in rat lung.

A neutral proteinase with endothelin (ET)-1 converting activity was identified in cytosol and membrane fractions prepared from rat lung, in a ratio of 1:4, respectively. The membrane-bound proteinase was solubilized by 0.5% 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) with an increase in specific activity, and then was characterized. The solubilized proteinase was capable of converting big ET-1 to ET-1 with an optimum pH of 6.5, and the conversion was dose-dependently suppressed by phosphoramidon (IC50 = 0.5 microM). The molecular mass of the proteinase was estimated to be about 500 kDa by gel filtration in the presence of 0.5% CHAPS. These results indicate that rat lung contains a phosphoramidon-sensitive neutral proteinase catalyzing conversion of big ET-1 to ET-1. The proteinase may be involved in the biosynthetic pathway of ET-1 in the lung and/or the conversion of circulating big ET-1.

Animals

Effects of nitroglycerin on ATP-induced Ca(++)-mobilization, Ca(++)-activated K channels and contraction of cultured smooth muscle cells of porcine coronary artery.

Extracellular application of ATP transiently increases the cytosolic-free Ca++ concentration ([Ca++]i) in cultured smooth muscle cells of porcine coronary artery, and this activates large conductance Ca(++)-activated K (Kca) channels. In the present study effects of nitroglycerin (NG) and 4-aminopyridine (4-AP) on [Ca++]; and contraction were studied. 4-AP blocked Kca channels and enhanced the rise of [Ca++]i with oscillation, which led to contraction of the cells. NG activated the Kca channels of 300 picosiemens and inhibited 4-AP-induced contraction and oscillation of [Ca++]i. These results suggest that the vasorelaxant effect of NG involves hyperpolarization of the cell membrane by activating the Kca channels. NG also cause rapid decrease of [Ca++]i during the Ca(++)-mobilization by ATP in Ca-free solution. Similar effects were observed with cyclic GMP, suggesting that the effects of NG on the Kca channels and [Ca++]i were mediated by cyclic GMP.

4-Aminopyridine

Lactate analyzer with continuous blood sampling for monitoring blood lactate during physical exercise.

To monitor changes in the concentration of blood lactate during physical exercise, we used an automated lactate analyzer based on an electro-enzymatic method with continuous blood sampling through a catheter. The lactate concentration was measured every 2 min; between measurements, the instrument was calibrated with a lactate standard. Ascorbic acid, bilirubin, hemoglobin, creatinine, uric acid, and glucose did not interfere with the measurements. The lactate concentrations in blood samples from apparently healthy subjects before and after exercise correlated well (r = 0.993) with results by the conventional enzymatic method. We measured the blood lactate concentrations in nine apparently healthy volunteers during exercise on a treadmill with an increasing workload. The point at which lactate concentrations started to increase was detected easily. Thus, the lactate analyzer is suitable for monitoring changes in blood lactate concentrations during exercise.

Autoanalysis

Signal-averaging electrocardiogram in patients with diabetes mellitus.

In order to detect silent impairment of the heart due to diabetes mellitus, the signal-averaging electrocardiograms (ECG) of 21 healthy subjects and 22 diabetic patients without ventricular tachycardia were compared. The QRS duration in the signal-averaging ECG was longer in diabetic patients than in the normal subjects (87.3 ms vs. 114.5 ms, p less than 0.01). Moreover, late potentials in the terminal portion of the QRS complex were observed in 7 diabetic patients (32%), but in only one normal subject (5%, p less than 0.01). These findings suggested that patients with diabetes mellitus frequently have intraventricular conduction disturbances, presumably due to diabetic microangiopathy.

Adult

Spatial fibre architecture of Mm. pectorales in macaques: their morphological, phylogenetical, and functional implications.

The pectoral muscles of the 2 monkeys, Macaca fuscata and M. fascicularis, were described particularly in the light of 3 dimensional fibre architecture. There existed throughout the muscles the rotation in the same direction and radiation of fibre bundles as well as the consecutive and multi-stratified structure; This architectural design suggested that the deep pectoral masses of the mammals were derived from the caudal portion of the primitive pectoral plane through fibre migration caused by the whole muscle rotation, probably in response to the functional necessity peculiar to the mammalian locomotion.

Animals

[Magnetocardiographic localization of an accessory pathway in patients with WPW syndrome].

The usefulness of magnetocardiography (MCG) in determining the location of an accessory pathway (Kent bundle) was examined by the isomagnetic map at the time of a delta wave, and by gated magnetic resonance imaging (MRI). MCG was performed at 36 points on the anterior chest wall in eight cases with Wolff-Parkinson-White (WPW) syndrome using a SQUID (superconducting quantum interference device) system with the second derivative gradiometer. Based on these records, isomagnetic maps during the QRS and T waves were constructed, and the depth of the accessory pathway from the coil was calculated mathematically. The locations of the accessory pathways were estimated using these data and the MRI findings. The locations of the accessory pathways thus determined were compared with findings obtained by body surface maps. A dipole directed towards the left was deduced, because the maximum was located more superiorly than the minimum in an isomagnetic map 10-40 msec after onset of the delta wave in cases with WPW syndrome, indicating an accessory pathway to be located in the right ventricle. A dipole directed towards the right was deduced, because the maximum was located more superiorly than the minimum in an isomagnetic map 10-40 msec after onset of the delta wave of cases with WPW syndrome indicating an accessory pathway to be located in the left ventricle. Assuming the electric current source is a single dipole, the location of a current dipole might be determined by positions of the maximum and the minimum in the isomagnetic maps. In the present study, the locations as determined by analysis of the isomagnetic map 40 msec after onset of the delta wave and the gated MRI were concordant with the findings obtained by body surface isopotential maps. Furthermore, some cases showed two opposing dipoles on the isomagnetic map at the peak of the T wave in lead II of the standard ECG leads; one directed to the left expressing normal repolarization; the other directed to the right presumably expressing repolarization of the myocardium which was excited by an impulse via the accessory pathway. The location of the current dipole as determined by analysis of the isomagnetic map at the peak of the T wave in lead II was nearly the same as the position of the current dipole as determined by analysis of the isomagnetic map 40 msec after onset of the delta wave.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Effect of magnesium sulfate on ventricular refractoriness and its efficacy for torsade de pointes.

The effect of magnesium sulfate on ventricular refractoriness and its efficacy for torsade de pointes (TdP) were studied in nineteen dogs. After the administration of quinidine sulfate (30 mg/kg), TdP was induced by ventricular pacing in ten of 19 dogs (52.6%), polymorphic ventricular tachycardia in seven (36.8%), ventricular fibrillation in two (10.5%). Quinidine sulfate caused significant increases in QTc interval, ventricular effective refractory period (ERP) and dispersion of ERP(dERP), and decrease in ERP/QT. Magnesium sulfate significantly increased ERP (p less than 0.01), but it did not change QT interval, resulting in significant increasing of ERP/QT (0.41 +/- 0.05 to 0.61 +/- 0.05, p less than 0.01). It decreased dERP but not significantly. Magnesium sulfate prevented the induction of TdP in eight of 10 dogs (80.0%) (30 mg/kg in four and 60 mg/kg in four). In conclusion, magnesium sulfate has value as first aid therapy for drug-induced TdP. If patients have ischemic heart disease or hypertension, we recommend infusion of magnesium for the initial therapy of TdP.

Animals

[Studies on the Rett syndrome. Part 2. Polysomnographic and neuroendocrinological studies].

The biogenesis of the Rett syndrome (RS) is unknown although there have been several reports suggesting some biochemical defect of the monoaminergic system in CNS. We performed all night polysomnography and neuroendocrinological tests in three cases of RS discovered on a surveillance study in Tokushima. The following results were obtained; 1) dissociation of sleep elements (stage 1-REM, stage 2-REM), 2) no increase in REMs/min with development, 3) abnormal patterns of BMs, TMs of each sleep stage, 4) paradoxical secretion of growth hormone (GH) and excessive secretion of prolactin in TRH provocation test, the absence of sleep enhancement of GH secretion, 5) progressive disfunction of autonomic nervous system during sleep. These results indicated that RS involves the functional disturbances of brain stem and hypothalamic monoaminergic regulatory systems.

Adolescent

[A case of pulmonary tuberculosis associated with adult respiratory distress syndrome during corticosteroid treatment of rheumatoid arthritis].

We reported a case of 64 year-old female patient of pulmonary tuberculosis associated with ARDS during corticosteroid treatment of Rheumatoid Arthritis. On admission her chief complaints were fever, fatigue and dyspnea. A chest roentgenogram showed diffuse alveolar infiltration consistent with pulmonary edema. Arterial blood gas studies showed severe hypoxemia. We clinically diagnosed so-called ARDS. Smears of sputum for acid fast bacilli were negative, but transbronchial lung brushing by bronchofiberscope revealed many acid fast bacilli. Intensive therapy with anti-tuberculosis drugs (INH, RFP, SM), high dose corticosteroid (methylprednisolone) therapy and mechanical ventilation was started. During the following 2 weeks, the PaO2 rose gradually and the alveolar infiltration on the chest roentgenogram disappeared. The experience of this case to emphasized the importance of suspecting this condition because pulmonary tuberculosis is a potentially curable cause of ARDS and it should also be emphasized that the good treatment effect could be expected with combined use of high dose corticosteroid and mechanical ventilation.

Arthritis, Rheumatoid

Vector U loop in patients with old myocardial infarction.

The U loop of the vectorcardiogram was examined qualitatively and quantitatively in 100 normal subjects and 67 patients with old myocardial infarction, using a direct-writing vectorcardiograph with memory function. In the control group, the U loop was directed to the left, anteriorly and inferiorly, and it was inscribed counterclockwise in the horizontal plane. In patients with anterior myocardial infarction, the U loop tended to be displaced to the right, and in patients with inferior myocardial infarction to the right and superiorly. The shape of the U loop in patients was also different from that of normal subjects. The maximum U vector was significantly smaller in magnitude both in patients with anterior and inferior myocardial infarction than that of normal subjects (p less than 0.01). In patients with ventricular aneurysm, the magnitude of the maximum U vector was significantly smaller and its direction was displaced more to the right and posteriorly than those without aneurysm (p less than 0.01). In standard 12-lead electrocardiogram (ECG), observation of the U wave in patients with old myocardial infarction was difficult, especially in the limb lead, because of the small size of the U wave. Therefore, vectorcardiographic observation may be more useful than electrocardiographic observation for the analysis of the U wave in patients with old myocardial infarction.

Adult

Effects of lidocaine and quinidine on post-repolarization refractoriness after the basic and premature action potentials: consideration of aim of antiarrhythmic drug therapy.

Antiarrhythmic drugs are often more effective in suppressing ventricular tachycardias than are background premature extrasystoles. The mechanism of action of these agents was examined by studies on the effects of lidocaine and quinidine on post-repolarization refractoriness of both basic and premature action potentials. In the absence of antiarrhythmic drugs, the excitability threshold was relatively constant after the end of repolarization of both basic and premature action potentials. In the presence of lidocaine or quinidine, the strength-interval curves were shifted to the right and superiorly, and the two drugs had different effects on the course of the strength-interval curve and Vmax recovery, presumably due to use-dependent V max block. Moreover, depressions of Vmax and excitability were more marked after the premature action potential than after the basic action potential. These results suggest that lidocaine and quinidine cause more depression of the excitability of second premature contractions than of first premature contractions, and also indicate that for protection against sustained ventricular tachycardias, it may not be necessary to suppress chronic premature ventricular contractions.

Action Potentials

Magnetic resonance imaging in autism: preliminary report.

MRI was performed for 18 autistic patients, 11 patients with uncomplicated mental retardation (MR) and 18 controls. In autism and MR, and altered left/right relationship of the frontal lobe volume was observed. The altered asymmetry was more severe in autism than in MR. The brain stem was smaller in MR than in the controls, and the right operculum was smaller in MR than in autism. These findings are consistent with the hypothesis that some autisms may involve a type of early developmental abnormality. Furthermore, our results suggest that autism may involve a type of structural brain impairment different from MR.

Autistic Disorder

Magnetocardiographic studies of ventricular repolarization in old inferior myocardial infarction.

Isomagnetic maps of 50 normal subjects (control group) and 23 patients with old inferior myocardial infarction (IMI group) were recorded in order to analyse T wave abnormalities in inferior myocardial infarction. The T wave of the magnetocardiogram (MCG) in the control group showed negative deflections in the left upper portion and positive deflections in the right lower portion, thus resulting in a T vector directed leftward and inferiorly. The T wave of the IMI group was flat or positive in the left upper portion and flat or negative in the right lower portion, suggesting a T vector directed superiorly. In addition, opposing dipoles were observed in 36.4% of the IMI group; i.e. one directed superiorly, presumably due to inferior myocardial ischaemia, and the other directed inferiorly due to normal repolarization. Localized T vector abnormalities could be detected by the MCG in some cases, in which coronary T waves of the standard electrocardiogram had returned to normal. Furthermore, multiple dipoles were more frequently observed in the isomagnetic map than in the isopotential map (5 vs. 15; P less than 0.01). These results suggest that the MCG is helpful in diagnosing myocardial ischaemia when this is not detectable on the electrocardiogram.

Adult