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Biomedical subjects

Y Masuda

Publications and source records attributed to Y Masuda.

At least 685 records · Page 38Linked to original sources

The neurotoxicity of phenobarbital and its effect in preventing pentylenetetrazole-induced maximal seizure in aging mice.

The effects of age on the neurotoxicity of phenobarbital and its anticonvulsant effect were examined in female BDF1 mice of different ages by means of a rotorod test and the pentylenetetrazole (PTZ)-induced maximal seizure, respectively. The minimal neurotoxic concentrations (MTCs) of phenobarbital in both plasma and brain evaluated by a rotorod test were 50% lower (p less than 0.05) in old (24-months-old) mice compared with the respective values in young (6-months-old) mice, while 12-months values were the highest of the three groups. Mice given some dosages of phenobarbital, particularly old (24-months-old) mice, died within the 15-min observation period after an i.p. injection of PTZ (150 mg/kg) without demonstrating a hindlimb extensor component (HLE) of maximal seizure. When these animals were classified as responders with regard to the anticonvulsant effect of phenobarbital, the minimal effective concentrations (MECs) in plasma and brain required for abolishing the PTZ-induced maximal seizure in old mice were only 10-20% those of young mice. Present results coupled with our past studies using electroshock seizure suggest that both the neurotoxicity and the efficacy of phenobarbital increase with age in mice.

Administration, Oral↗

A novel class of potential central nervous system agents. 3-Phenyl-2-(1-piperazinyl)-5H-1-benzazepines.

A series of 3-phenyl-2-piperazinyl-5H-1-benzazepines and related compounds were synthesized and evaluated for potential neuroleptic activity. The preparation of these compounds was carried out by 2,3-dichlorination of 3-phenyl-2,3,4,5-tetrahydro-1H-1-benzazepin-2-ones with phosphorus pentachloride followed by amination and concurrent dehydrochlorination. Compounds having the 4-chloro or 4-fluoro substituent in the 3-phenyl group were found to possess the neuroleptic-like activity. Among them, 2-(4-methyl-1-piperazinyl)-3-(4-fluorophenyl)-5H-1-benzazepine dihydrochloride (23) was comparable to chlorpromazine in inhibiting exploratory activity, conditioned avoidance response, and self-stimulation response and more potent than chlorpromazine in antagonizing apomorphine-induced emesis. These neuroleptic effects may be based on an antidopaminergic property of the compound. In causing catalepsy or ptosis, however, 23 was weaker than chlorpromazine. Therefore, this ring system is of interest as a novel class of neuroleptics. Some compounds having the 7-chloro or 7-bromo substituent showed potent anticonvulsant effects against maximal seizures induced by electroshock or pentylenetetrazole.

Animals↗

Determination of the phosphorylation sites of calmodulin catalyzed by casein kinase 2.

Calmodulin is specifically phosphorylated by casein kinase 2 (CK 2), but not by casein kinase 1, A kinase, or C kinase. In the present report, the stoichiometry of the phosphorylation of calmodulin by CK 2 in the presence and absence of polylysine and its phosphorylation sites were examined. In the absence of polylysine, the radioactive phosphate incorporated into calmodulin by CK 2 was only 0.01 mol/mol and the phosphorylation occurred at Ser-101. In the presence of polylysine, 1.2 mol of radioactive phosphate was incorporated into 1 mol of calmodulin. In this case, Thr-79 in addition to Ser-101 was phosphorylated, but Ser-81 was not. The sequence around the phosphorylated Thr is Asp-Thr(P)-Asp-Ser-Glu-Glu-Glu-.

Amino Acid Sequence↗

Galactose inhibition of auxin-induced growth of mono- and dicotyledonous plants.

Galactose inhibited auxin-induced cell elongation of oat coleoptiles but not that of azuki bean stems. Galactose decreased the level of UDP-glucose in oat coleoptiles but not in azuki bean hypocotyls. Glucose-1-phosphate uridyltransferase activity (EC 2.7.7.9), in a crude extract from oat coleoptiles, was competitively inhibited by galactose-1-phosphate, but that enzyme from azuki bean was not. A correlation was found between inhibition of growth by galactose and inhibition of glucose-1-phosphate uridyltransferase activity by galactose-1-phosphate using oat, wheat, maize, barley, azuki bean, pea, mung bean, and cucumber plants. Thus, it is concluded that galactose is converted into galactose-1-phosphate, which interferes with UDP-glucose formation as an analog of glucose-1-phosphate.

Journal Article↗

Intensified IgA mesangial deposits after administration of sheep anti-type IV collagen serum in mice.

Sheep anti-type IV collagen serum was intravenously administered to male mice of the BALB/c, C3H and ddY strains, and their kidneys were morphologically studied monthly for 10 months thereafter. By immunofluorescence, the sheep IgG was seen to have immediately become conjugated to the glomeruli, mainly in a mesangial pattern. Successively, autologous mouse C3 and IgG appeared with the same type of distribution. Within 3 to 4 months after the start of the experiment, mouse IgA also appeared in the mesangium, especially in ddY mice. The intensity and frequency of mesangial IgA deposition and the serum IgA level increased with time in this strain. BALB/c and C3H mice also showed the same tendency of mesangial IgA deposition, although to a lesser degree. In summary, it was concluded that mesangial IgA deposition was due to non-immunological local trapping, on the basis of the results obtained by ELISA analysis of the sera and renal eluate. Although the ddY mouse is known to show spontaneous mesangial IgA deposition associated with a high serum IgA level with aging, these characteristics were much accelerated and intensified by this antiserum treatment. The relation of this observation to the pathogenesis of human IgA nephritis is discussed.

Animals↗

Rapid determination of norepinephrine, dopamine, serotonin, their precursor amino acids, and related metabolites in discrete brain areas of mice within ten minutes by HPLC with electrochemical detection.

A rapid and simple chromatographic procedure using HPLC with electrochemical detection is described for simultaneous determination of the substrates from precursor amino acids to metabolites related to synthesis and metabolism of three monoamine neurotransmitters--norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT, serotonin)--in discrete brain areas of the mouse. Under the present instrumental and mobile phase conditions, the procedure permits simultaneous determination of three monoamines (NE, DA, and 5-HT), two precursor amino acids (tyrosine and tryptophan), and four respective metabolites (3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid) within 10 min in one chromatographic run. By varying column temperature, this procedure also permits simultaneous determination of 10-14 monoamine-related substrates including the nine substrates described above within 15-21 min. The validity of the present procedure is demonstrated by analyzing the effect of an alpha 2-adrenergic agonist (clonidine) and an alpha 2-antagonist (yohimbine) in mouse hypothalamus.

3,4-Dihydroxyphenylacetic Acid↗

Transient abnormal septal motion after non-surgical closure of the ductus arteriosus.

Abnormal septal motion on M mode echocardiography was seen in eight of 16 patients soon after non-surgical closure of the ductus arteriosus. Ten to twenty-nine months after the procedure the abnormal septal motion had disappeared spontaneously. The cross section of the left ventricular cavity was circular both when septal motion was abnormal and when it was normal. Cross sectional echocardiography showed that there was an exaggerated anterior swinging motion of the heart in systole in patients with abnormal septal motion on the M mode recordings. The left ventricular end diastolic diameter before closure was significantly larger, and its reduction after closure was more pronounced in those with abnormal septal motion than in those without. This suggested that the abnormal septal motion was associated with relief of long standing left ventricular volume overload. It is suggested that acute shrinkage of the heart caused temporary laxity of the pericardium, and consequently more movement of the heart within the thorax. The return of normal septal motion suggests that the pericardium gradually shrank to accommodate the smaller heart.

Adult↗

The role of interstitial collagens in cleft formation of mouse embryonic submandibular gland during initial branching.

An interstitial collagenase was purified from the explant medium of bovine dental pulp and was shown to degrade collagens I and III but not IV and V. The enzyme halted cleft initiation in the epithelium of 12-day mouse embryonic submandibular glands in vitro, indicating the active involvement of interstitial collagens in the branching morphogenesis. Transmission electron microscopic observation of the intact 12-day gland without any clefts showed the scattered localization of a few collagen fibrils at the epithelial-mesenchymal interface of the bulb and also revealed the presence of numerous microfibrils around the stalk. Collagen bundles were regularly seen close to the wavy basal lamina at the bottom of clefts of the intact 13-day gland and 12-day gland cultured for 17 h under normal conditions. Mesenchymal cells were found in the clefts together with the frequent localization of peripheral nerve fibres and capillary endothelial cells. The collagen bundles were more often observed in the 12-day gland cultured in the presence of bovine dental pulp collagenase inhibitor, which had been shown to enhance cleft formation. In contrast, collagen fibrils were rarely found at the epithelial-mesenchymal interface of the 12-day gland cultured in the presence of Clostridial or bovine dental pulp collagenase. The findings indicated that the formation of interstitial collagen bundles is essential to form clefts in the epithelium both in vivo and in vitro.

Animals↗

Clinical and immunological study of IgA nephropathy before and after tonsillectomy.

The clinical course and the changes of the levels of immunological factors after tonsillectomy in several cases of IgA nephropathy associated with chronic tonsillitis are presented in this paper. In the first study, here called Part I, 16 cases of IgA nephropathy were observed with regard to the clinical course and the changes of immunological factors after the operation. Postoperatively, proteinuria disappeared in 9 cases and improved in 3 and the levels of serum IgA, the circulating immune complex (CIC) and serum polymeric IgA decreased. In the next study, Part II, 10 cases of IgA nephropathy were investigated regarding the changes of the levels of serum IgA, C3, C4, CH50, APCH50 and CIC after the provocation test and tonsillectomy. A tendency of decreasing levels of C3 and APCH50 combined with an increase of CIC was observed within one week after provocation. Decreases in the levels of serum IgA, polymeric IgA, C3 and APCH50 were also observed after the operation. From these results, it is suggested that the tonsillar lesion has a tendency to continue the pathogenetic effect on the disease and exacerbate its clinical symptoms.

Adolescent↗

Effects of carbon disulfide, diethyldithiocarbamate, and disulfiram on drug metabolism in the perfused rat liver.

The effects of carbon disulfide (CS2), diethyldithiocarbamate (DTC) and disulfiram (DS) on hepatic drug metabolism were studied in a noncirculating and hemoglobin-free rat liver perfusion system using p-nitroanisole (p-NA) as a substrate. Infusion of 1 mumol of CS2 into a normal rat liver instantaneously lowered the free p-nitrophenol (p-NP) concentration in the effluent perfusate; however, the effects on the levels of its glucuronide and sulfate conjugates were much less marked. The suppression of p-NP production by CS2 was also observed in livers isolated from phenobarbital (PB)- and 3-methylcholanthrene (3-MC)-treated rats; to a greater extent, in the normal and 3-MC groups. Partial recovery was observed in the normal and PB-treated groups, but it was slow and slight in the 3-MC-treated group. Infusion of DTC, up to 20 mumol, did not lower free p-NP levels, but a slight transient increase was noted, especially in the 3-MC-group. Using 50 mumol of DTC, a slight suppression resulted. DS, up to 20 mumol, did not decrease p-NP production, but rather gradually increased it, especially in the 3-MC-treated groups. Without the p-NP infusion, about 60-70% of the infused DS (10 mumol) was recovered in the effluent perfusate as DTC plus its glucuronide conjugate, the formation of the latter being greatly enhanced by the inducer treatments and markedly suppressed during the p-NP infusion. In this paper, these results are discussed with regards to the mechanisms of drug metabolism inhibition by DS administration.

Animals↗

Oxidation of diethyldithiocarbamate to disulfiram by liver microsomes in the presence of NADPH and subsequent loss of microsomal enzyme activity in vitro.

Oxidation of diethyldithiocarbamate (DTC) to disulfiram (DS) by liver microsomes was tested in vitro by using a copper-DTC chelate formation reaction after the conversion of DS to DTC by glutathione (GSH). In the presence of NADPH, microsomes produced DS from DTC in both the free and microsome-bound forms, the former being greater than the latter. DS production was dependent on NADPH and DTC concentrations, and incubation time. Increases in microsomal concentrations, up to a certain level, also increased the free and total DS production. NADH was only somewhat effective, both the exposure to a nitrogen atmosphere and heat-denaturation of the microsomes suppressed the reaction. Preincubation of microsomes with both DTC and NADPH markedly decreased aniline hydroxylase, p-nitroanisole O-demethylase and glucose-6-phosphatase activities, and moderately decreased NADH-ferricyanide and NADH-cytochrome c reductase, but NADPH-cytochrome c reductase was minimally affected. DTC alone had only slight effects on the activities. DS also decreased these enzyme activities, particularly glucose-6-phosphatase; the loss of NADPH-cytochrome c reductase activity being protected in the presence of NADPH. GSH almost completely prevented the loss of microsomal enzyme activities induced by DTC and NADPH except for the drug metabolizing activities, in which protection was incomplete. The microsomal oxidation of DTC to DS could play a role in the action of DS in the liver, since DS is rapidly degradated to DTC in vivo.

Animals↗

[Flow imaging of the cardiovascular system using magnetic resonance imaging].

Blood flow images by magnetic resonance imaging (MRI) using a 0.25 T unit were evaluated for nine normal volunteers and 108 subjects with a variety of cardiovascular abnormalities. Using the non-gated short-spin echo (SE) technique, blood flow in the cardiovascular systems was not imaged in the normal volunteers. Using end-systolic and end-diastolic SE techniques for the normal subjects, blood flow in the cardiac chambers was not clearly imaged. Blood flow in the ascending aorta and aotric arch often did not appear in the gated SE images of the normal subjects. However, blood flow in the descending aorta was often observed in the gated SE images. Blood flow imaging was demonstrated by both non-gated and gated SE techniques in regions where blood flow was relatively slow; for example, in the left atrium of mitral stenosis, in an aortic aneurysm, in a false lumen of an aortic dissection, and in the left ventricle having old myocardial infarction. Using the non-gated inversion recovery (IR) technique, no blood flow was imaged in the cardiovascular system except in the left atrium of one case with mitral stenosis. Using the non-gated short SE technique, there was good correlation between the thrombus formation and the presence of blood flow images in the left atria of 17 patients with mitral stenosis, and in the aneurysmal portions of the aorta or in the false lumens of aortic dissection of 18 patients. It was suggested that mural thrombi in such diseases were related to the relatively slow blood flow. Blood flow imaging easily distinguished stagnant blood flow from mural thrombi using non-gated short SE, end-systolic SE, and IR techniques. Thus, blood flow imaging using MRI should become an important means of evaluating the cardiovascular system.

Adult↗

[Right ventricular function in cardiovascular disease evaluated by magnetic resonance imaging].

The usefulness of ECG-gated magnetic resonance imaging (MRI) in evaluating right ventricular architecture and function was assessed by measuring right ventricular wall thickness, wall motion, and areas of the right ventricular cavities of seven normal subjects and 46 with cardiac disease, including atrial septal defect (ASD: six cases), hypertrophic cardiomyopathy (HCM: 19), dilated cardiomyopathy (DCM: eight), and old myocardial infarction (OMI: 13 cases). A superconductive MRI system was used. Transverse images at the level of the tricuspid valve were obtained for measurements. ECG-gated MRI clearly showed the right ventricular myocardium throughout the cardiac cycles and facilitated measuring wall thickness and cross-sectional areas of the right ventricular cavity in all subjects. In normals the mean value and standard deviation of the anterior wall thickness of the right ventricle and the area index of the right ventricular cavity at end-diastole were 3.4 +/- 0.7 mm and 10.6 +/- 1 cm2/m2, respectively. The anterior and lateral walls and tricuspid annulus moved inward to the right ventricular cavity in systole, and the excursion of the lateral wall and tricuspid annulus was larger than those of the anterior wall. The interventricular septum (IVS), however, moved outward to the left ventricle in systole. The anterior wall thickness of the right ventricle in patients with HCM was 5.8 +/- 1.4 mm thicker than that of normal subjects. In contrast to normals, the area index of the right ventricular cavity was larger in patients with ASD (18.4 +/- 5.4 cm2/m2) and smaller in patients with HCM (9.1 +/- 1.6 cm2/m2). The IVS moved inward in all patients with ASD and in several patients with HCM. The anterior and lateral wall motion was decreased in patients with ASD and DCM.

Adult↗