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Biomedical subjects

K Manabe

Publications and source records attributed to K Manabe.

At least 73 records · Page 4Linked to original sources
PubMed1995

Hyperpolarization induced by vasoactive substances in intact guinea-pig endocardial endothelial cells.

1. The responses of guinea-pig endocardial endothelial (EE) cells to various vasoactive substances were investigated in either the small tissue preparation or freshly isolated cells using the patch clamp technique. 2. The mean resting potential of the EE cell was -44 mV in the small tissue preparation, and applications of ATP, ADP, AMP, adenosine, histamine and substance P induced transient hyperpolarizations of -22, -21, -9, -10, -23 and -15 mV, respectively. The membrane potential of EE cells failed to respond to acetylcholine, bradykinin, thrombin, atrial natriuretic peptide, vasopressin and serotonin. 3. The whole-cell voltage clamp of dissociated cells revealed a transient increase of K+ conductance underlying the ATP and histamine responses. The agonist-induced current showed no time-dependent change during voltage steps. The response was showed no time-dependent change during voltage steps. The response was prevented by adding 10 mM EGTA to the pipette solution. 4. In the cell-attached single channel recordings, ATP induced transient K+ channel activities having a slope conductance of 34 pS. In inside-out patches, similar K+ channels were activated by applying Ca2+ of more than 0.1 microM. 5. These findings are consistent with the idea that the Ca(2+)-dependent K+ channel is involved in the hyperpolarizing response of EE cells, as described in vascular endothelial cells.

Adenosine↗
PubMed1995

Classification of ion channels in the luminal and abluminal membranes of guinea-pig endocardial endothelial cells.

1. The ion channels on both the luminal and abluminal membranes of endocardial endothelial (EE) cells were separately recorded using the patch clamp technique in the guinea-pig heart. 2. The major population consisted of two types of non-selective cation channels, which showed open probabilities of 0.21 and 0.33 at the resting potential, and conductances of 36 and 11 pS, respectively. 3. The next major class was Cl- channels with an ohmic conductance of 409 pS. The channel was quiescent in the cell-attached mode but was activated by strong depolarization after excising the patch membrane. 4. The channels activated by intracellular Ca2+ were mainly K+ channels showing a 34 pS slope conductance and, less frequently, Ca(2+)-dependent K+ channels having a large conductance (210 pS). The inward rectifier K+ channel (32 pS) was also observed. 5. The non-selective cation channels were recorded on the luminal membrane, but scarcely on the abluminal membrane, suggesting an active transport of K+ and Na+ across the endocardium. 6. The resting membrane conductance of the EE cells may be provided mostly by non-selective cation channels and 34 pS Ca(2+)-dependent K+ channels.

Animals↗
PubMed1995

Comparison of the kinetic disposition and metabolism of E3810, a new proton pump inhibitor, and omeprazole in relation to S-mephenytoin 4'-hydroxylation status.

We studied the kinetic disposition and metabolism of E3810 [(+/-)-sodium 2-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl ]-1H- benzimidazole], a new proton pump inhibitor, and omeprazole in 15 Japanese male volunteers, six of whom were poor metabolizers and nine of whom were extensive metabolizers of S-mephenytoin. All received once-daily 20 mg doses of E3810 or omeprazole for 7 days in a randomized crossover manner, with a 3-week washout period between the two trial phases. The parent drugs and their principal metabolites in plasma and urine were measured on days 1 and 7 after drug administration. The mean values for area under the plasma concentration-time curve (AUC) of omeprazole were 6.3- and 4.4-fold greater, whereas those of E3810 were 1.8- and 1.9-fold greater in poor metabolizers than in extensive metabolizers after the first and final doses, respectively. Although the mean AUC values for both drugs were significantly (p < 0.01 or p < 0.05) greater in poor metabolizers than in extensive metabolizers, the difference in the AUC between the two groups was smaller after E3810 than after omeprazole administration. The AUC of omeprazole tended to increase with the repeated doses in extensive metabolizers, whereas no such change was observed for E3810. The urinary excretions of the principal metabolite(s) of two proton pump inhibitors also reflected the data derived from plasma samples in relation to S-mephenytoin 4'-hydroxylation status. We conclude that the metabolism of two proton pump inhibitors is under coregulatory control of S-mephenytoin 4'-hydroxylase (CYP2C19), but that the magnitude of CYP2C19-mediated metabolism appears to differ between the two drugs. In contrast to omeprazole, the metabolism of E3810 is less saturable in extensive metabolizers during the repetitive dosings.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Comparison of the interaction potential of a new proton pump inhibitor, E3810, versus omeprazole with diazepam in extensive and poor metabolizers of S-mephenytoin 4'-hydroxylation.

OBJECTIVE: To compare the interaction potential of E3810, [(+/-)-sodium 2-[[4-(3-methoxpropoxy)-3-methylpyridin-2-yl]methylsulfinyl] -1H-benzimidazole] a new proton pump inhibitor, and omeprazole with diazepam in relation to S-mephenytoin 4'-hydroxylation status. STUDY DESIGN: Fifteen healthy male volunteers consisting of six poor metabolizers and nine extensive metabolizers of S-mephenytoin 4'-hydroxylation participated in the study, where two poor and three extensive metabolizers each as a group were randomly allocated to one of the three different treatment sequences with a 3-week washout period among the three trial phases. Each volunteer received an oral once-daily dose of E3810 (20 mg), omeprazole (20 mg), or placebo for 23 days and an intravenous dose (0.1 mg/kg) of diazepam on posttreatment day 8. Plasma concentrations of diazepam and demethyldiazepam were measured up to 16 days after the administration of diazepam. RESULTS: Diazepam was more slowly metabolized in the poor metabolizers than in the extensive metabolizers. No significant effects of E3810 and omeprazole on any kinetic parameters of diazepam were observed in the poor metabolizers. In the extensive metabolizers, omeprazole significantly decreased the mean clearance of diazepam and increased its half-life, area under the plasma concentration-time curve, and mean residence time compared with E3810 and placebo (p < 0.05 or 0.01), whereas no changes in these kinetic parameters were observed during the treatment with E3810. Omeprazole significantly increased the mean area under the plasma concentration-time curve (0-16 days) of demethyldiazepam in the extensive metabolizers compared with placebo (p < 0.01), whereas E3810 significantly increased it in the poor metabolizers compared with omeprazole or placebo (p < 0.05). CONCLUSION: The results indicate that E3810 as a substrate goes less toward S-mephenytoin 4'-hydroxylase (CYP2C19) and has a much weaker, if any, potential to interact with diazepam compared with omeprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Long-term change of anti-acetylcholine receptor antibody in patients with myasthenia gravis after thymectomy.

Anti-acetylcholine receptor antibody (AChR Ab) plays an important role in the pathogenesis of myasthenia gravis (MG). We investigated the change of anti-AChR Ab titer after thymectomy of 10 MG patients including five patients whose age at onset was younger than 16 years. Anti-AChR Ab titer was increased in four of six patients with remission and three of four patients without remission. Change of anti-AChR Ab titer in individual patients showed an increase occurred 1-4 years after thymectomy. It is likely that thymectomy influences immune response and induces autoreactive lymphocytes and autoantibodies.

Adolescent↗
PubMed1995

Evaluation of left ventricular diastolic hemodynamics from the left ventricular inflow and pulmonary venous flow velocities in hypertrophic cardiomyopathy.

We evaluated the characteristics of left ventricular diastolic hemodynamics in hypertrophic cardiomyopathy (HCM) by measuring left ventricular inflow (LVIF) and pulmonary venous flow (PVF) velocities in 62 patients with asymmetric septal hypertrophy and 34 normal controls. The patients were divided into four groups according to the LVIF pattern and left ventricular end-diastolic pressure (LVEDP): 1) the pseudonormalization group; 13 patients with the ratio of peak atrial systolic (A) to early diastolic (E) LVIF velocity (A/E) < or = 1 and LVEDP > or = 15 mm Hg, 2) the normal pattern group; 10 patients with the A/E < or = 1 and LVEDP < 15 mm Hg, 3) the relaxation failure group; 25 patients with the A/E > 1, and 4) the mid-diastolic wave group; 14 patients with a mid-diastolic wave. The peak early diastolic LVIF velocities in the pseudonormalization, relaxation failure and mid-diastolic wave groups were significantly smaller than in the control group. The deceleration time from the peak of the E wave and the isovolumic relaxation time were significantly prolonged in the relaxation failure and mid-diastolic wave groups. The peak diastolic PVF velocity in the relaxation failure and mid-diastolic wave groups was significantly decreased, and was significantly increased in the pseudonormalization group. The peak atrial systolic PVF velocity was significantly increased in all patients with HCM, particularly in the pseudonormalization group. LVEDP was the highest in the pseudonormalization group, followed by the mid-diastolic wave, relaxation failure and normal pattern groups, in that order. In conclusion, combined analysis of the LVIF and PVF provides useful information regarding various abnormalities of left ventricular diastolic hemodynamics in patients with HCM.

Adult↗
PubMed1995

The first heart sound in atrial septal defect with reference to atrioventricular valve motion and hemodynamics.

To clarify the characteristics of the first heart sound in atrial septal defect (ASD) and its pathophysiological basis, 17 patients with ASD associated with incomplete right bundle branch block (IRBBB) and 7 with isolated IRBBB were studied using phonoechocardiography and Doppler echocardiography. Fifteen of the 17 ASD patients also were studied following surgical closure of the defect. Indices were compared among the preoperative ASD, postoperative ASD, and IRBBB groups including: P-Q intervals, loudness of the mitral and tricuspid component of the first heart sound (IM, IT), end-diastolic closing excursions of the mitral and tricuspid valves (Mx, Tx), and mitral and tricuspid inflow velocities during early diastole and atrial contraction. There were no significant differences in the P-Q intervals among these 3 groups. IM was attenuated, and IT was accentuated in ASD compared with IRBBB. Postoperatively, IM was augmented in all but 1 patient and IT was attenuated in all patients. Mx was significantly smaller, and Tx was significantly larger in ASD than in IRBBB. Postoperatively, Mx was significantly increased and Tx was significantly reduced; the maximal mitral inflow velocity during atrial contraction was increased while the maximal tricuspid inflow velocity was significantly reduced. Thus, the first heart sound in ASD is characterized by an attenuated mitral component and an accentuated tricuspid component. Hemodynamic alterations and consequent changes in closing energies of the atrioventricular valves probably account for these features.

Adolescent↗
PubMed1995

Differential vocalization in budgerigars: towards an experimental analysis of naming.

In Experiment 1, 3 budgerigars (Melopsittacus undulatus) were trained with food reinforcement to make low- or high-frequency calls in response to different color stimuli, C1 and C2 (a color-naming task), using a gradual response-differentiation procedure and an automatic call-recognition system. Thus, a call within a certain frequency band was reinforced in the presence of C1 ("C1 call"), and a call within a different band was reinforced in the presence of C2 ("C2 call"). In Experiment 2, all 3 budgerigars were trained in a form-to-color matching-to-sample task, alternating trial by trial with either the color-naming task (2 birds) or an identity color matching-to-sample task (1 bird). Sample stimuli for the new matching-to-sample task were forms (F1 or F2) and comparisons were the same two colors (C1 and C2). Given Sample F1 or F2, birds had to make a call to produce Comparison Pair C1 and C2. With F1 as the sample, a peck on C1 was reinforced; with F2 as the sample, a peck on C2 was reinforced. Although no particular call was specified in the presence of F1 and F2, 2 birds made the C1 call in the presence of F1 and the C2 call in the presence of F2. In Experiment 3, the bird that failed to match form and color calls in Experiment 2 and another bird were first trained in a color-to-form matching-to-sample task: C1 to F3 and C2 to F4. In this task, to produce the comparison pair of forms, a high call (or low for the other bird) was required in the presence of C1, and a low call (or high) was required in the presence of C2. Both birds were then trained with an identity matching-to-sample task in which sample and comparison stimuli were the same two forms, F3 and F4. Trials on the identity task alternated with the color-to-form trials. Although no particular call was required in the presence of Samples F3 and F4, both birds came to make the C1 call in the presence of F3 and the C2 call in the presence of F4. Our technique promises to be useful for the study of emergent vocal relations in budgerigars and other animals.

Animals↗
PubMed1995

[Transesophageal echocardiographic study on the mechanisms of mitral regurgitation in hypertrophic cardiomyopathy: comparison with sigmoid septum].

Transesophageal echocardiography was performed to elucidate the mechanisms of mitral regurgitation (MR) in 40 patients with hypertrophic cardiomyopathy with asymmetric septal hypertrophy, 15 obstructive and 25 nonobstructive, and the organic changes of the mitral leaflet were compared to those of 30 patients with sigmoid interventricular septum. Thirty subjects without cardiac diseases served as the control group. Transthoracic and transesophageal echocardiography were performed in all subjects to measure the following: left ventricular dimension, interventricular septal thickness and peak velocity at the left ventricular outflow tract by transthoracic echocardiography; the lengths and the thicknesses of the rough zone of the anterior and posterior mitral leaflets at mid-diastole and the distance between the tip of the posterior papillary muscle and the anterior mitral annulus by transesophageal echocardiography. The presence of systolic anterior motion of the mitral complex, contact between the anterior mitral leaflet and the interventricular septum during diastole, and the occurrence of mitral valve prolapse (MVP) were also investigated. The maximum area and timing of MR during systole was measured by M-mode color Doppler technique. The following results were obtained. 1. MR was observed in 35 (88%) of the 40 patients with hypertrophic cardiomyopathy. The maximum regurgitant area in the obstructive group was significantly greater than in the other groups, and the regurgitation was frequently pansystolic. 2. The lengths of both mitral leaflets at mid-diastole were significantly greater in both groups with hypertrophic cardiomyopathy than in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

[Changes in pulmonary venous and transmitral flow velocity patterns after cardioversion of atrial fibrillation].

The time course of recovery of left atrial mechanical function after electrocardioversion of atrial fibrillation was examined in 25 patients with atrial fibrillation by recording pulmonary venous and transmitral flow velocities and interatrial septal motion during atrial systole within a day (16 +/- 5 hours) and ten days after cardioversion of atrial fibrillation by transesophageal and transthoracic Doppler and M-mode echocardiography. There were 6 patients with hypertension, 4 with ischemic heart disease, 2 with alcoholic heart, 5 with dilated cardiomyopathy, and 8 without underlying heart disease. The peak velocities of the atrial systolic waves of the transmitral and pulmonary venous flow velocities (A and PVA, respectively) and first systolic wave (PVS1) of pulmonary venous flow, durations of both atrial systolic waves, and amplitude of interatrial septal motion during atrial systole increased significantly ten days after cardioversion compared with those measured within a day of cardioversion in all patients except the 5 patients with dilated cardiomyopathy. Peak velocity of the second systolic wave (PVS2) of pulmonary venous flow increased, and that of the early diastolic and diastolic waves (E and PVD, respectively) of transmitral and pulmonary venous flow decreased ten days after cardioversion compared with those within a day of cardioversion. These results suggested that active atrial systolic (A and PVA) and relaxant (PVS1) parameters obtained from transmitral and pulmonary venous flow velocities are good indicators of left atrial mechanical function after cardioversion of atrial fibrillation.

Adult↗
PubMed1995

HLA DPB polymorphism in primary sclerosing cholangitis and primary biliary cirrhosis.

In recent years there has been an increasing interest in the link between susceptibility to autoimmune liver disease and genes of the HLA system, although the role of the DPB1 locus in British patients has only been investigated in autoimmune hepatitis. The aim of the current study was to determine the distribution of DPB1 alleles in a large series of British patients with the two other autoimmune liver diseases, primary biliary cirrhosis and primary sclerosing cholangitis, and compare the allele frequencies obtained with those of a geographically matched control group. Polymerase chain reaction sequence-specific oligonucleotide probing was used to assign 18 DPB1 alleles in 82 patients with primary biliary cirrhosis (PBC), 71 patients with primary sclerosing cholangitis (PSC), and 103 controls. The frequencies of the DPB1 alleles were not significantly different comparing patients and controls. However, two important observations were made. Firstly, in primary sclerosing cholangitis, the previously reported association with the haplotype A1-B8-DR3-DQ2 does not extend to the DPB1 locus, suggesting that the genetic determinants of susceptibility for this disease lie closer to the DRB loci. Secondly, in primary biliary cirrhosis there is evidence that the reported association with DR8-DQB1*0402 includes the DPB1*0301 allele. The weak HLA association reported here is in contrast with recent data from Japan, where susceptibility is strongly linked to a particular amino acid residue encoded by the DPB1*0501 allele. These data clearly demonstrate that the alleles of the DPB1 locus are not associated with susceptibility to or protection from either primary biliary cirrhosis or primary sclerosing cholangitis in British patients.

Adult↗
PubMed1995

Histopathologic studies of innervation of normal and prolapsed human mitral valves.

We evaluated the distribution of the nerves in valve tissue of humans to clarify the relationship between mitral valve prolapse and autonomic nerve dysfunction. We studied 15 autopsy specimens of normal mitral valve, 10 prolapsed mitral valves, five each of normal tricuspid, aortic, and pulmonary valves, and three prolapsed mitral valves obtained at cardiac surgery. Immunohistochemical studies utilized the avidinbiotin peroxidase complex (ABC) method and several nerve-related antigens: 1) S-100 protein, glial fibrillary acidic protein (GFAP), and neurofilament protein (NFP) as markers of glial and Schwann cells of the nervous system; 2) choline acetyltransferase (ChAT) to identify cholinergic nerve endings; 3) neuropeptide Y (NPY), a neuropeptide that is distributed in accordance with sympathetic nerves; and 4) calcitonin gene-related peptide (CGRP), a neuropeptide that is distributed in accordance with afferent nerves. Distribution of adrenergic nerve fibers was also examined by fluorescence method. Morphology of nerve endings of the normal mitral valve was studied by electron microscopy. In normal valves, distributions of S-100 protein, GFAP, and NFP immunoreactivities were clearly visible along the subendocardial site on the coaptation aspect of the base-to-body portion of each valve, regardless of the kind of valve. In contrast, there was only a scanty distribution of these reactivities on the physiologic coaptation area of the tip. In prolapsed mitral valves, there was no distribution of S-100-positive protein or other nerve-related antigens in areas of the valve with myxomatous degeneration. Distribution of CGRP, ChAT, and NPY immunoreactivities, and adrenergic fluorescence, were the same as those of the nerve-related antigens in both normal and prolapsed mitral valves. Electron microscopic study of the atrial aspect of normal mitral valves revealed numerous small axons with aggregations of small clear vesicles, indicating cholinergic features. The results suggest that the subendocardial site on the atrial aspect at the middle portion of the mitral valve is rich in nerve endings, including the afferent nerves, and that mechanical stimuli from this area caused by abnormal coaptation in mitral valve prolapse may produce an improper circuit in autonomic nerve function between the central and mitral valve nervous systems.

Adult↗
PubMed1994

Supra- and juxtatrigeminal inhibitory premotor neurons with bifurcating axons projecting to masseter motoneurons on both sides.

Inhibitory neurons participating in the bilateral disynaptic inhibition of jaw-closing motoneurons by stimulation of unilateral trigeminal sensory branches were searched for in the reticular formation around the trigeminal motor nucleus in cats anaesthetized with pentobarbital. Extracellular recordings were made from neurons which responded orthodromically after a monosynaptic latency to single shock stimulation of the ipsilateral infraorbital and/or inferior alveolar nerves. Direct inhibitory connection with contralateral masseter motoneurons was demonstrated in reticular neurons by the spike-triggered averaging technique, i.e., by averaging the intracellular potentials of a contralateral masseter motoneuron with respect to spontaneously occurring spikes of a reticular interneuron. By intraaxonal injection of neurobiotin, electrophysiologically identified inhibitory premotor reticular neurons were found to project to and to terminate in the trigeminal motor nuclei on both sides. Termination in the contralateral motor nucleus was demonstrated for four neurons that showed the peripheral input pattern stated above. The results provide hard evidence for contralaterally projecting interneurons in the reticular formation, participating in peripherally evoked disynaptic inhibition of masseter motoneurons on the contralateral side. Given the previously reported findings that the supratrigeminal region contains neurons which project to the ipsilateral motor nucleus and mediate disynaptic inhibition of masseter motoneurons, it is suggested that the supratrigeminal region contains bilaterally projecting interneurons, mediating peripherally evoked disynaptic inhibition of masseter motoneurons on both sides.

Animals↗
PubMed1994

A conformational change associated with the phototransformation of Pisum phytochrome A as probed by fluorescence quenching.

Dynamic quenching of the two lifetime component tryptophan fluorescence of Pisum phytochrome has revealed differential accessibility of certain residues. Both acrylamide and Tl+ ions showed preferential exposure of some tryptophans in Pfr-phytochrome. Greater kq's for Pfr are, however, in contrast with values for Avena phytochrome in which Pr-->Pfr conversion impedes Tl+ access. The Pr short lifetime component was more accessible to Cs+; however, the long component accessibility was approximately 2-fold higher in Pfr. 2-Hydroxy-5-nitrobenzyl bromide (HNB-Br) modification of native Pisum phytochrome was used to reduce the total number of fluorescent tryptophans. The absence of the fluorescence contributions of the three residues which reacted with HNB-Br in both photoisomers increased the Tl+ Ksv's for Pr and Pfr. The two additional HNB-Br modifications specific for Pfr resulted in a reversal of the Stern-Volmer plots relative to the unmodified protein. The regions around four of the 10 tryptophans may represent conformationally photoresponsive areas in Pisum phytochrome A. Furthermore, topographic changes associated with the phytochrome phototransformation are not confined to the 58-kDa chromphore domain, and they involve most if not all of the region from Trp-365 to Trp-787. We also provide evidence that the protein conformation in this region is not completely conserved between Pisum and Avena phytochromes.

2-Hydroxy-5-nitrobenzyl Bromide↗
PubMed1994

T-cell receptor constant beta germline gene polymorphisms and susceptibility to autoimmune hepatitis.

BACKGROUND/AIMS: Susceptibility to autoimmune hepatitis is associated with HLA A1-B8-DR3 and DR4. T-Cell antigen receptors (TCR) are candidates for genetic susceptibility to autoimmune diseases because they recognize peptide antigens in the context of HLA molecules. The aim of this study was to investigate the possible role of TCR germline polymorphisms in susceptibility to autoimmune hepatitis. METHODS: TCR constant beta (C beta) region polymorphisms were investigated using restriction fragment length polymorphism analysis in 60 unrelated northern European White patients with autoimmune hepatitis and 190 racially and geographically matched healthy controls. RESULTS: A significant increase in the frequency of homozygous status for the 10-kilobase/Bgl II of the TCR C beta was found in the patients compared with controls (42% vs. 21%; corrected P value [Pc] < 0.0075; relative risk [RR] = 2.8). This difference was more pronounced in patients without HLA-DR3 and DR4 (50% vs. 14%; Pc < 0.015; RR = 6.1). Furthermore, heterozygosity for TCR C beta was significantly decreased in early-onset patients presenting with HLA-DR3 before 30 years of age (12% vs. 48%; Pc < 0.03; RR = 0.16). CONCLUSIONS: The present findings provide evidence that genetic susceptibility to AIH may be determined by both the TCR C beta genes and HLA genes and that the genotype of the TCR C beta may be one of the factors in influencing the age at onset of disease.

Adolescent↗