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Biomedical subjects

T Matsubara

Publications and source records attributed to T Matsubara.

At least 469 records · Page 26Linked to original sources
PubMed1985

[Effect of a new sleep inducer, 1H-1,2,4-triazolyl benzophenone derivative 450191-S on rat liver drug-metabolizing enzyme system].

The effect of a new sleep inducer, 450191-S, on the hepatic drug-metabolizing enzyme system was examined using rats and compared with those of nitrazepam and phenobarbital. Cytochrome P-450-dependent 7-alkoxycoumarin O-dealkylation activity determined using liver homogenate and isolated microsomes increased after successive oral administrations of 450191-S, and induction of the enzyme system was observed by administration of 150 approximately 200 mg/kg of the drug for at least 3 approximately 5 days. Normal activity was recovered with withdrawal of the drug for 3 approximately 5 days after induction of the hepatic enzyme system. Administration of higher amounts of 450191-S (200 approximately 600 mg/kg/day) for 3 days caused remarkable increases in the O-dealkylase and UDPGA-glucuronyltransferase activities and cytochrome P-450 and b5 contents. Similar changes in the hepatic enzyme system were observed with administration of nitrazepam (200 approximately 600 mg/kg for 3 days, p.o.) or phenobarbital (10 approximately 40 mg/kg for 3 days, i.p.). We concluded that the inducing activity of 450191-S is almost the same as that of nitrazepam, but weaker than that of phenobarbital. When the hepatic enzyme system was induced by the administration of either 450191-S or phenobarbital, the pentobarbital-induced sleeping time was shortened with increasing doses of the drugs. On the other hand, sleeping time was prolonged by the administration of another type of inducer, beta-naphthoflavone. The results suggest that the inductive pattern of 450191-S is similar to that of phenobarbital.

Animals↗
PubMed1984

Slow inactivation of Vmax in guinea pig ventricular myocardium.

Measurements of maximum upstroke velocity (Vmax) of guinea pig ventricular action potentials were used to investigate the effect of prolonged depolarization on the inactivation and recovery kinetics of cardiac sodium channels. Membrane potential before stimulated upstrokes was controlled by passing current across a sucrose gap. Two phases of inactivation ("slow" and "ultra-slow") having kinetics and voltage dependence different from the commonly observed fast inactivation process were observed. Ultra-slow inactivation developed exponentially with a time constant of several minutes between -60 and -20 mV. In contrast, slow inactivation developed with a time constant of 1-6 s between -60 and 40 mV. Under steady-state conditions slow and ultra-slow inactivations were virtually absent at -85 mV, while 50% of Vmax underwent slow inactivation at approximately 10 mV and 50% underwent ultra-slow inactivation at approximately -40 mV. Recovery from slow inactivation occurred exponentially with a time constant of about 2 s at -70 to -85 mV and 0.7 s at -100 mV. Recovery from ultra-slow inactivation was not completely characterized but was complete within 20 s at -85 mV. No significant effect of external [K+] (1-10 mM) on slow inactivation was found. The results suggest the existence of two additional inactivated states of the cardiac sodium channel distinctly different from the fast inactivated state.

Action Potentials↗
PubMed1984

The localization and secretion of type IV collagen in synovial capillaries by immunohistochemistry using a monoclonal antibody against human type IV collagen.

The localization and the secretion of type IV collagen in synovial capillaries have been investigated by detecting the antigenic determinant of the major triple helix of human type IV collagen. Type IV collagen was indicated to be localized mainly in the lamina densa of basement membranes (BM) and to be secreted by both endothelial cells and pericytes. The pericytes secreted this collagen to both surfaces facing endothelial cells and the interstitial connective tissue. On the contrary, the direction of type IV collagen secretion by the endothelial cells was strictly confined to one side, namely towards the surface facing the BM. The absence of the antigenic determinant in rough endoplasmic reticulum and Golgi apparatus of the endothelial cells and pericytes indicated that the major triple helix of type IV collagen is mainly formed in the secretory vesicles after budding from the Golgi apparatus.

Adult↗
PubMed1984

Chemical reactivations of inactivated acetylcholinesterase after 2-PAM therapy in fenitrothion-poisoned rat and rabbit.

We investigated the reactivation of inactivated acetylcholinesterase (AChE) after 2-PAM therapy in acute fenitrothion poisonings of two species of rat and rabbit. By single treatment with 2-PAM carried out immediately after fenitrothion administration, the significant reactivations of inactivated AChE in red blood cell (RBC) and brain as well as inactivated cholinesterase (ChE) in plasma were observed at 2 h after administration of 20 mg/kg fenitrothion in rat, while these reactivations became less in rats severely poisoned with 500 mg/kg fenitrothion. Although these significant reactivations disappeared 6 h after the single treatment with 2-PAM, the repeated treatments with 2-PAM induced the prolongation of the reactivations of inactivated AChEs and ChE. These results suggest that 2-PAM would be more effective to light poisoning with fenitrothion, and that the repetition of 2-PAM treatment would be very important to obtain the sufficient antidotal actions. In rabbits as well as rats, the considerable reactivations of inactivated AChEs in RBC and brain and inactivated ChE in plasma were observed by the single treatment with 2-PAM in fenitrothion poisoning. These reactivations in brain AChE indicate that 2-PAM can penetrate the blood brain barrier of both rat and rabbit, despite its quaternary character.

Acetylcholinesterase↗
PubMed1984

Spontaneous reactivation of mouse plasma cholinesterase after inhibition by various organophosphorus compounds.

We investigated the spontaneous reactivation of mouse plasma cholinesterase (ChE) after inhibition by various organophosphorus compounds. The remarkable spontaneous reactivations during storage at 24 degrees C were observed in plasma ChE prepared 30 min after oral administration of three O,O-dimethyl organophosphorus compounds, i.e. malathion, methylparathion and cyanox; while the spontaneous reactivation did not occur after inhibition by tolclofos-methyl, one of O,O-dimethyl organophosphorus compounds. The plasma ChEs inhibited by surecide, salithion and leptophos, which contain no O,O-dimethyl moiety, were not reactivated or only slightly so. These results suggest that a more sufficient attention should be paid in the determination of activity of plasma ChE inhibited by O,O-dimethyl organophosphorus compounds than that of plasma ChE inhibited by organophosphorus compounds without O,O-dimethyl moiety, since plasma ChE inhibited by the organophosphorus compounds with O,O-dimethyl moiety, except for tolclofos-methyl, was more easily reactivated, and the correct activity of inhibited plasma ChE can not be obtained without attention to the spontaneous reactivation. Furthermore, these spontaneous reactivations were examined by using butyrylthiocholine as well as acetylthiocholine as a substrate, and results showed that there was little difference between the spontaneous reactivations observed in using acetylthiocholine and butyrylthiocholine. So, it is concluded that these spontaneous reactivations take place only in pseudo ChE.

Animals↗
PubMed1984

Hepatic 7-alkoxycoumarin O-dealkylase in mice: induction by beta-naphthoflavone of hepatic enzyme activity.

Hepatic 7-alkoxycoumarin O-dealkylation activities in control and beta-naphthoflavone-pretreated mice were determined. The O-demethylation and O-deethylation activities of 7-alkoxycoumarin in control mice were almost the same values, while the O-depropylation activity was lower than those of the other reactions. The O-dealkylase activity varied markedly among the 18 strains of mice surveyed, and strain-dependent differences in the cytochrome P-450 content were also detected among the strains. beta-Naphthoflavone induced O-dealkylation activity, especially O-deethylation and O-depropylation activities, only in ddY, DS and its substrains (A2-3, A3-1, C1-2 and Nh/+). C3H/He and C57BL/6J strains, but not in DBA/2, BALB/c and KYF/2 strains. The former strains of mice are thus classified as "responsive strains" to beta-naphthoflavone and the latter as "non-responsive strains". The O-dealkylase activity in other strains of mice were not clear in responsiveness to beta-naphthoflavone. The hepatic cytochrome P-450 content in responsive strains also increased upon pretreatment of the animals with beta-haphthoflavone. The results indicate marked strain differences in basal and beta-naphthoflavone-induced activity of hepatic 7-alkoxycoumarin O-dealkylase in mice.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1984

Relationship between regional myocardial blood flow and tissue ATP content in acute ischemia.

This study was undertaken to determine the relationships between myocardial mitochondrial function, regional myocardial blood flow (MBF), and tissue ATP content in acute ischemia. Fifty-one anesthetized dogs were used in the tests. MBF was measured by the H2 gas clearance method in order to define the ischemic area, during periods of coronary occlusion of 10, 20, 60, and 90 min. The correlation between MBF and myocardial ATP content in the ischemic area was positive and significant in each group (r = 0.54-0.82). The ATP content in the true ischemic area (where MBF was less than 20 ml/min/100 Gm) decreased significantly even after 10 min of occlusion, but mitochondrial function decreased only after 20 min of coronary occlusion when compared to the nonischemic area. Although ischemia induces mitochondrial dysfunction, a very short period of ischemia did not cause significant disturbance of mitochondrial function. Moreover, in the areas with MBF of 20-40 ml/min/100 Gm, the ATP content began to decrease 60 min after occlusion, whereas 10 or 20 min of occlusion did not reduce the ATP content. These results suggest that normal maintenance of ATP levels depends not only on MBF itself but also on the duration of ischemia plus the degree of damage to mitochondrial function, and that critical blood flow, defined as the minimum flow necessary to maintain the level of myocardial ATP, varies with the duration of ischemia.

Acute Disease↗
PubMed1984

Electron and immunoelectron microscopic investigation of basal lamina thickening in synovial capillaries and post-capillary venules in rheumatoid arthritis.

Capillaries and post-capillary venules in the synovium obtained from 12 rheumatoid arthritis (RA) patients have been investigated by electron microscopy and immunoelectron microscopy with a monoclonal antibody against human type IV collagen, which is one of the major basal lamina (BL) components. The level of BL thickening in RA synovial vessels is roughly parallel with that of cellular exudation. The BL thickening may be due to excessive production of BL components, in which the accelerated rate of death and replenishment of endothelial cells and pericytes plays an important role. These cells may not only produce a single layer of BL in their life-time but also produce excessive amounts of BL components to make several layers in their life-time.

Adult↗
PubMed1984

[A study on the ruptured Valsalva sinus aneurysm using two-dimensional echocardiography].

We visualized the Valsalva sinus aneurysm ruptured into the right ventricle using two-dimensional echocardiography, and analyzed the blood flow by pulsed Doppler technic. Cross-sectional echocardiography was performed on 11 patients with right sinus aneurysm protruding into the right ventricle. The age of the examined subjects ranged from 17 to 40 years. Ten of the 11 revealed a ruptured aneurysm of the right sinus of Valsalva into the right ventricle. Nine of the 11 had ventricular septal defect and five were associated with aortic regurgitation. Pulmonic regurgitation was recognized in one case. The diagnosis was made by cardiac catheterization and angio-cardiography in all cases and was confirmed by cardiac surgery in nine patients. In this study, we employed an electronic (SSH-11A) or mechanical sector scanning system (SSL-51H) for cross-sectional echocardiography. In order to clearly visualize an aneurysm, the cross-section of the left ventricular long-axis was obtained from a slightly lower and more sagittal position than the standard method. In addition, the short axis cross-section of the aortic root was also examined. Furthermore, a pulsed Doppler technic was applied to three patients using a Doppler unit SDS-10A combined with SSH-11A. In all patients, an aneurysm of the right sinus of Valsalva was seen to protrude into the right ventricle by two-dimensional echocardiography. Furthermore, the ruptured orifice of the aneurysm was clearly visualized in ten cases. The shape of the aneurysm was tubular in ten cases and saccular in the remaining one. A continuous blood flow of wide band pattern was recorded in the right ventricle near the ruptured orifice in two of the examined three cases and a disturbed diastolic flow was noted in a saccular aneurysm. In conclusion, two-dimensional echocardiography is useful to visualize an aneurysm of the right sinus of Valsalva ruptured into the right ventricle and a pulsed Doppler technic is greatly contributed in detecting localized disturbed flow due to the ruptured aneurysm.

Adolescent↗