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Biomedical subjects

I Ito

Publications and source records attributed to I Ito.

At least 145 records · Page 8Linked to original sources

Roles of protein kinases in neurotransmitter responses in Xenopus oocytes injected with rat brain mRNA.

Microinjection of rat brain mRNA in Xenopus oocytes induced acetylcholine, neurotensin, serotonin, and glutamate receptors in the cells. These receptors stimulate an intracellular reaction pathway, including G-protein activation, inositol trisphosphate (IP3) formation, and Ca2+-dependent Cl- channels. In the present study, we examined the roles of several protein kinases in these responses by means of inhibitors and activators of these kinases. Isoquinolinesulfonamides, inhibitors of protein kinases, caused no current responses and affected no receptor-mediated responses when injected into the oocytes at low doses (30-50 pmol), which inhibit cyclic nucleotide-dependent kinases or kinase C specifically, but abolished the receptor-mediated responses at a higher dose (300 pmol), which inhibit most protein kinases nonspecifically. Calmodulin inhibitors blocked the receptor-mediated responses strongly. Activation of cyclic nucleotide-dependent kinases or kinase C by injection of cAMP (or cGMP) or perfusion with phorbol esters caused no direct current responses but suppressed receptor-mediated responses. Current responses triggered by IP3 injection were not suppressed by these treatments. These results suggest that cAMP- (or cGMP-)dependent kinases or kinase C may not be involved in the pathway directly but may modulate it by inhibiting the initial part of the pathway (receptors, G-proteins, and/or phospholipase C), and they suggest that calmodulin may most likely be involved in the activation of Ca2+-dependent Cl- channels.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Characterization of glutamate receptors induced in Xenopus oocytes after injection of rat brain mRNA.

Xenopus oocytes in which poly(A)+ mRNA isolated from rat brains were previously injected, exhibited at least 3 categories of current responses to excitatory amino acids. They were oscillatory responses to glutamate (Glu) or quisqualate (QA), smooth large responses to kainate (KA), and smooth small responses to Glu and QA. Oscillatory responses were mediated by a metabotropic type of Glu receptor which is coupled to a G-protein but not directly to an ionic channel. Amplitudes of smooth Glu responses and smooth QA responses were similar in size, and were not additive to each other, suggesting a common receptor mediating both responses. L-Glutamylglycine inhibited KA responses in a competitive manner without affecting smooth Glu/QA responses, indicating that KA and smooth Glu/QA responses were mediated by separate receptors. From these results, it was concluded that the injection of rat brain mRNA induced at least 3 different glutamatergic receptors: receptors mediating (a) KA responses and (b) smooth Glu/QA responses, and (c) the metabotropic Glu receptor. The former two may most likely correspond to Glu receptor subtypes preferring KA and QA, respectively, as seen in the brain.

Animals↗

Classification of hypertrophied hearts in essential hypertension: evaluation by left ventricular wall stress and adrenergic responses.

Left ventricular mass, fractional shortening, and end systolic wall stress (mechanical indices) measured by echocardiography and the response of fractional shortening and end systolic wall stress to the infusion of isoproterenol (0.02 microgram/kg/min for 5 min) (a non-mechanical index) were studied in 57 patients (mean (SD) age 49(8)) with essential hypertension. Nineteen patients had subnormal end systolic wall stress (group 1), 25 patients had normal end systolic wall stress and slightly increased left ventricular mass (group 2A), and 13 patients had normal end systolic wall stress and considerably increased left ventricular mass (group 2B). Plasma noradrenaline concentration was higher in group 2B than in the other groups. When end systolic wall stress was greater than 12 g/cm2 this variable showed a significant inverse linear relation with fractional shortening before isoproterenol infusion. The inotropic response to isoproterenol was measured as the increase of fractional shortening corrected for the decrease of end systolic wall stress (delta fractional shortening/--delta end systolic wall stress). The mean (SD) change in delta fractional shortening/--delta end systolic wall stress was significantly larger in group 1 (1.40 (0.60) cm2/g) than in group 2A (0.85 (0.39) cm2/g), and was significantly larger in group 2A than in group 2B (0.56 (0.15) cm2/g). In patients with hypertensive hypertrophy with subnormal end systolic wall stress (inappropriate hypertrophy) the beta adrenergic response is increased; in hypertensive hypertrophy with normal end systolic wall stress (appropriate hypertrophy), however, it is normal, or becomes reduced as plasma noradrenaline increases.

Adult↗

[Cases of severe methyl bromide poisoning residing above a warehouse].

Methyl bromide has been widely used in Japan to fumigate grains and wood. One death and 3 cases of hospitalization resulted from exposure to methyl bromide at place of residence. These 4 cases were not employed and were members of one family living above a warehouse, the ground level of this building was a warehouse where herbs were stored and the second floor was their living area. On the 13th of May 1978 at 7:00 p.m., the herbs were fumigated with methyl bromide gas. The fumigator used 15 kg of methyl bromide (2 cylinders), a quantity far greater than usual. It is assumed that the concentration in the warehouse was between 10,000-15,000 ppm. Early in the morning on the 16th of May (3 days later), one of the family members, a 12-year-old girl, developed severe convulsions, and later 2 others also had severe convulsions, while the other suffered from marked mental confusion. The serum or plasma bromide ion level ranged from 280 to 600 ppm. The results of the clinical laboratory test showed that GOT exceeded the normal level in 3 out of the 4 cases. Moreover, LDH activity was above the normal range in 3 cases and CPK activity was increased in all the cases.

Adult↗

[Electrocardiographic changes and arrhythmias in the elderly].

To evaluate the relationship between aging and electrocardiographic abnormalities and arrhythmias, conventional surface 12 leads ECG findings were analyzed. The study group consisted of a total of 3,174 cases (1,778 men and 1,396 women, 17-87 years) without apparent organic heart diseases. The proportion of normal ECG progressively decreased with advancing age; it reached to the minimum of 20.0% in male and 22.7% in female after the age of 75. Frequency of supraventricular and ventricular premature complexes increased with advancing age as well as atrial fibrillation, left and right bundle branch block and left anterior hemiblock. Sinus bradycardia (less than 50/min) and the WPW syndrome did not follow this general trend but the former increased with advancing age after 55. Second and third-degree AV blocks were very rare in this study population. Right bundle branch block with left anterior hemiblock was not observed before age of 35, which may be regarded as a possible consequence of advanced age. Supraventricular and ventricular premature beats, and atrial fibrillation were more frequent in men than in women, but only in the older age stratum. Intraventricular conduction disorders were generally more common in men than in women. However, left bundle branch block was more frequently observed in female than in male in the older age stratum. The prolongation of QTc by oral IA antiarrhythmic drugs was observed after the age of 65. Thus, it was confirmed that aging might be important factor in abnormal findings and appearance of arrhythmias in conventional surface 12 lead ECGs.

Adolescent↗

Tricuspid regurgitation diagnosed by intravenous digital subtraction angiography.

In spite of numerous available diagnostic methods, controversies concerning the precise diagnosis of tricuspid regurgitation (TR) still remain. In right ventriculography, catheter placement may modify tricuspid valvular function. Though noninvasive Doppler echocardiography is a useful method, it is sometimes too sensitive for clinical use. Furthermore, it is not applicable to cases in which ultrasound penetration is limited. In this study, we evaluated TR using intravenous digital subtraction angiography (DSA), which can provide good images even in cases with poorly recorded echocardiograms. For this study, we placed a catheter in the superior vena cava. Cardiac DSA examinations were performed in one hundred and one patients with heart disease. We injected 35 ml of contrast medium at a speed of 18 ml/sec via a catheter introduced in the superior vena cava. DSA images by continuous mode were obtained in the RAO projection for 15-20 sec. Sequential DSA images were observed and analyzed by time-density curves of the regions of interest (ROI) which were placed in the right ventricle (RV) and inferior vena cava (IVC). Doppler echocardiography was performed for 16 cases in which TR was suspected. Of these, phonocardiography with jugular pulse tracing was recorded for 14 and contrast echocardiography were performed for six, respectively. In cases without evidence of TR, regurgitation of contrast medium into the IVC during RV systole was not recorded by the DSA method. In cases of clinically-proven TR, regurgitation into the IVC during RV systole was observed. Thus, this was considered a diagnostic feature of positive TR using the DSA method, and 13 of the 16 cases undergoing Doppler echocardiography were diagnosed as having TR using the DSA method. The severity of TR was categorized as mild, moderate and severe according to analyses of time-density curves. The severity established by the DSA method showed a close correlation with the clinical severity of TR. Doppler echocardiography was negative for TR in two of the 13 cases, but positive for TR in two of the 16 suspected cases only by the Doppler method. In cases of moderate to severe TR diagnosed by the DSA method, jugular pulse tracings showed a regurgitant wave. By contrast echocardiography, TR was evident only in cases of severe TR diagnosed by the DSA method. In conclusion, the DSA method proved useful for diagnosing TR.

Adult↗

[Type IV Ehlers-Danlos syndrome associated with mitral valve prolapse: a case report].

A 52-year-old male patient with the Ehlers-Danlos syndrome (familial hypermobility of the joints, hyperextensibility of the skin and atrophic cutaneous scars) was evaluated because of a mitral regurgitant murmur. Echocardiography demonstrated marked mitral valve prolapse of the both leaflets and vegetation-like thickening of the anterior leaflet of the mitral valve. Two-dimensional color flow mapping showed severe mitral regurgitation. This patient had also acrogeria-like facial appearance and very thin skin (subcutaneous veins were readily visible). He developed repeated rupture of radial, ulnar and middle cerebral arteries and expired. A histological section of the ruptured ulnar artery demonstrated no infectious process. In view of the joint hyperextensibility, very thin skin, characteristic facial appearance and the spontaneous occurrence of three successive ruptures of peripheral arteries, a diagnosis of Ehlers-Danlos syndrome (type IV) was made. Although mitral valve prolapse is reportedly common in type I, II and III Ehlers-Danlos syndrome, this report emphasizes that it may also occur in patients with type IV Ehlers-Danlos syndrome and the relevant literatures are reviewed.

Echocardiography↗

Sudden death in hypertrophic cardiomyopathy, a guideline to prevention in daily life.

To establish guidelines for individuals with hypertrophic cardiomyopathy (HCM) to follow in their daily lives and minimize the chance of sudden death (SD), circumstances of SD in 24 autopsied definite HCM cases were compared with those with 905 autopsied cases of other heart diseases. Circumstances of symptoms experienced in daily activities of 35 age-matched surviving HCM cases were also studied. In the autopsied HCM cases, SD occurred during exertion more frequently (79.2%) than in the other autopsied cardiac patients (22.7%). Sudden changes in pace or movement accompanied by mental excitement, such as hurrying to board a train, were more frequent causes of SD in HCM (47.4%) than in other cardiac patients (8.3%). In the surviving HCM cases, symptoms of distress occurred frequently during very hard work or with sudden rapid movement. Thus, one probable daily guideline for HCM sufferers would appear to be not only to eliminate very hard work but also to lead mentally and physically quiet and relaxed life.

Adolescent↗

Variable neurohumoral and hemodynamic responses to exercise in patients with exertional angina: influence of the severity of coronary artery disease.

To assess neurohumoral and hemodynamic responses to exercise in patients with exertional angina, we measured plasma norepinephrine (NE) concentrations in 23 patients with exertional angina (with no heart failure) and compared the results with their coronary arteriographic findings. The 23 patients were divided into two groups: 14 cases with multiple vessel disease (MVD) and 9 cases with one-vessel disease. At resting state there were no significant differences between the two groups in levels of NE. At maximal exercise there were no significant differences between the groups in increases of heart rate, blood pressure, and rate-pressure product, but exercise-induced increase of plasma NE (%) was significantly larger in MVD (131.6 +/- 95.4%) (mean +/- SD) than in one-vessel disease (69.0 +/- 45.3%) (p less than 0.01). In conclusion, plasma NE responses to exercise differ between patients with multiple vessel disease and patients with one-vessel disease.

Angina Pectoris↗

Impaired left ventricular rapid filling during exercise in patients with hypertrophic cardiomyopathy.

The influence of exercise on left ventricular diastolic filling was evaluated in 14 patients with hypertrophic cardiomyopathy (HCM) and 14 normal controls (NC) by dynamic exercise echocardiography. Using X-Y digitizer and computer, normalized peak rate of change of the left ventricular dimension during systole (pVs) and the rapid filling phase (pVd) were determined from the left ventricular echocardiograms at rest and during exercise when heart rate reached 100 beats/min. At rest and during exercise, pVs was significantly higher in HCM (3.2 +/- 0.4/s at rest, 4.3 +/- 1.4/s during exercise) than in NC (2.4 +/- 0.5/s at rest, 3.0 +/- 0.4s during exercise) (p less than 0.001, p less than 0.001, respectively), but pVd in HCM (4.2 +/- 1.0/s at rest, 5.8 +/- 1.0/s during exercise) was not significantly different from that in NC (4.1 +/- 1.0/s at rest, 6.0 +/- 0.7/s during exercise). The ratio of pVd to pVs (pVd/pVs) in HCM did not show significant increment during exercise (1.35 +/- 0.38 to 1.43 +/- 0.35), though that ratio in NC was significantly increased by exercise (1.67 +/- 0.22/s to 1.97 +/- 0.19/s, p less than 0.001). There was no correlation between pVd and the degree of left ventricular hypertrophy. These results suggest that diastolic reserve to exercise is depressed in HCM and that other factors besides left ventricular hypertrophy may account for diastolic abnormality.

Adult↗

Aneurysm of patent ductus arteriosus in an adult case: findings of cardiac catheterization, angiography, and pathology.

A 42-year-old male was admitted to our hospital for evaluation of a left precordial continuous murmur. Results of catheterization revealed a step-up of oxygen content in the pulmonary arteries and the calculated left-to-right shunt flow was 40% of the pulmonary arterial flow. Furthermore, aortography unexpectedly revealed an aneurysm of the patent ductus arteriosus. During surgery, the aneurysm was discovered to arise from the frontal wall of the ductus arteriosus, and histological observation showed focal necrosis and mucoid degeneration of the media of the aneurysmal wall in contrast to a thickened intimal fibroelastosis of the adjacent ductal wall. This is presumed to be the first adult case of patent ductal aneurysm ever reported in which antemortem diagnosis and surgical treatment were successfully conducted. Our case may suggest that the fragility of the ductal wall following the structural change in an incomplete closing process is considered as a potential pathogenesis of ductal aneurysm formation.

Adult↗

Neurotensin and acetylcholine evoke common responses in frog oocytes injected with rat brain messenger ribonucleic acid.

1. The intracellular reaction mechanism underlying electrophysiological responses evoked by neurotensin (NT) was studied using Xenopus laevis oocytes injected with poly (A)+ messenger ribonucleic acid (mRNA) isolated from rat brains. 2. A few days after the injection of mRNA, oocytes were found to acquire sensitivity to NT and substance P. 3. Under voltage-clamp conditions (-60 mV), application of NT to mRNA-injected oocytes produced transient and oscillatory inward currents which began after a delay of several tens of seconds. These inward currents were accompanied by an increase in membrane conductance. 4. NT receptors on mRNA-injected oocytes showed essentially the same pharmacological properties as those of native NT receptors. 5. The NT response showed desensitization and was not readily recovered even after extensive washing of cells for more than 30 min. 6. NT response was suppressed when the muscarinic acetylcholine (ACh) response of the same cell, which was also induced by the same mRNA, was desensitized by a large dose of ACh. 7. NT response and ACh response showed many similarities: they were both inhibited by pertussis toxin and intracellular ethyleneglycol-bis-(beta-aminoethylether) N, N'-tetraacetic acid (EGTA), mimicked by intracellularly injected inositol 1, 4, 5-trisphosphate (InsP3), and suppressed when cell response to InsP3 was desensitized by a large dose of InsP3. Reversal-potential analyses indicated that both responses were mediated by an increase in membrane permeability to Cl-. 8. It is concluded that NT responses and muscarinic ACh responses of Xenopus oocytes induced by rat brain mRNA may most likely share a common reaction mechanism. The reaction sequence includes the activation of receptors, activation of inhibitory guanine nucleotide-binding regulatory protein, production of InsP3, intracellular Ca2+ mobilization, and increased membrane permeability to Cl-.

Acetylcholine↗

Effects of coronary collaterals on regional myocardial function during temporary coronary occlusion and hypoxic coronary perfusion.

The effects of coronary collaterals on regional myocardial function during temporary ischemia and hypoxia were studied in 12 open-chest dogs. Using an ultrasonic dimension gauge, systolic segment shortening in the left anterior descending coronary artery (LAD) area was measured at 1 min after the following three experimental conditions: LAD occlusion and LAD hypoxic perfusion with nonoxygenated solutions at two different pressures (60 mmHg and 120 mmHg). Collateral function was assessed by both LAD diastolic retrograde pressure and the percentage of increase in left circumflex coronary flow at 1 min after LAD occlusion. Systolic segment shortening decreased less with hypoxic perfusion than with occlusion, however, this beneficial effect on regional contraction was greater at a perfusion pressure of 60 mmHg than at one of 120 mmHg. The magnitude of decrease of systolic shortening was variable among individual dogs but correlated linearly with each of the two collateral function indexes, not only during occlusion but also during hypoxic perfusion. In conclusion, the preventive effect of hypoxic coronary perfusion on the early decline of regional myocardial function, in comparison to the changes seen during ischemia, may depend on coronary collaterals in addition to its washout effect on metabolites. In order to maintain myocardial function, perfusion pressure should be at an optimal level.

Animals↗