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Biomedical subjects

K Satoh

Publications and source records attributed to K Satoh.

At least 1,045 records · Page 58Linked to original sources

[A clinical study on imipenem/cilastatin sodium in the field of pediatrics].

A clinical study on imipenem/cilastatin sodium (MK-0787/MK-0791) was carried out and the following results were obtained. MK-0787/MK-0791 was used for treatment of a total of 33 patients and clinical effectiveness, bacteriological efficacy and adverse reactions were evaluated. The clinical effects were excellent in 1 case, good in 21 cases and fair in 2 cases in a total of 24 cases with respiratory tract infections, were excellent in 5 cases and good in 1 case in a total of 6 cases with urinary tract infections, and were good in 2 cases and fair in 1 case in a total of 3 cases with gastroenteritis. Causative organisms isolated from 11 patients were 1 strain of Gram-positive cocci and 10 strains of Gram-negative bacilli. Ten out of 11 strains were eradicated for an eradication rate of 91%. The clinical efficacy was confirmed in 11 cases for an efficacy rate of 100%. The bacteriological study has shown that MK-0787/MK-0791 has a strong antimicrobial activity. No side effects were observed. There was only one abnormal laboratory finding, i.e., a case of eosinophilia.

Bacterial Infections↗

Distribution of central cholinergic neurons in the baboon (Papio papio). I. General morphology.

The morphological characteristics of cholinergic neurons in the central nervous system (CNS) of the baboon (Papio papio) were studied by choline acetyltransferase (ChAT) immunohistochemistry and acetylcholinesterase (AChE) pharmacohistochemistry. The distributions of central cholinergic neurons as visualized by these two histochemical techniques were similar in most, but not all regions of the brain and spinal cord. Based upon these observations, central cholinergic neurons that are immunoreactive to ChAT and intensely stained for AChE by the pharmacohistochemical procedure can be divided into four major groups: (1) those in the caudate nucleus, putamen, nucleus accumbens and anterior perforated substance. These ChAT-containing and AChE-intense neurons are large and multipolar, and are scattered throughout these structures. (2) The rostral cholinergic column, which consists of a continuous mass of cholinergic perikarya situated in the medial septal nucleus, nucleus of the diagonal band, and nucleus basalis (Meynert). The ChAT-immunoreactive and AChE-intense cell bodies of the nucleus basalis are a prominent feature in the basal forebrain of the baboon. The labeled neurons are large, multipolar, and hyperchromic and show a tendency to aggregate in cell clusters. These cells are distributed within the full extent of the substantia innominata, often being associated with subcortical fiber networks such as the medullary laminae of the globus pallidus. (3) The caudal cholinergic column, which consists of a continuous group of cholinergic neurons in the caudal midbrain and pontine tegmentum. The rostral component of this group of cells is the nucleus tegmenti pedunculopontinus (subnucleus compacta) and it extends caudally to include the laterodorsal tegmental nucleus. Compared to that in other species the nucleus tegmenti pedunculopontinus in the baboon appears to occupy a relatively greater volume and is composed of a greater number of cholinergic neurons. The cells of the caudal column are large and hyperchromic. (4) Nuclei of origin of somatic and visceral efferents of the cranial nerves (III, IV, V, VI, VII, IX, X, XI, XII) and spinal nerves. In addition to these major cholinergic cell groups, a small population of ChAT-positive and AChE-intense cell bodies can be observed at the floor of the fourth ventricle and in lamina VII and X of the cervical cord. The present findings indicate that although some differences exist, the overall distribution and morphological features of cholinergic cell bodies identified in the baboon brain and spinal cord are similar to those demonstrated previously in investigations of the rhesus monkey and nonprimates.

Acetylcholinesterase↗

Distribution of central cholinergic neurons in the baboon (Papio papio). II. A topographic atlas correlated with catecholamine neurons.

The topographic distribution of central cholinergic and catecholaminergic neurons has been investigated in the baboon (Papio papio). The perikarya were mapped on an atlas through the brain and spinal cord employing sections processed for acetylcholinesterase (AChE) pharmacohistochemistry coupled with choline acetyltransferase (ChAT) immunohistochemistry or aqueous catecholamine-fluorescence histochemistry. Compared with subprimates, there is a remarkable increase in the volume occupied by and the number of cholinergic cells contained in the nucleus basalis and nucleus tegmenti pedunculopontinus (subnucleus compacta). The elaboration of these parts of the cholinergic system is accompanied by a large extension of catecholaminergic cell groups in the midbrain (groups A8-A10), particularly the substantia nigra (pars compacta), and in the dorsolateral pontine tegmentum (A5-A7 complex). Although cholinergic and catecholaminergic soma generally occupy distinctly different regions of the brain, a close apposition of cholinergic and noradrenergic neurons occurs in the dorsolateral pontine tegmentum. In the peripeduncular region ChAT-positive cells and green fluorescent neurons of the A6-A7 complex form parallel lines and do not intermingle as has previously been demonstrated in the cat. Two distribution patterns, aggregated or disseminated, are another common feature of central cholinergic and catecholaminergic perikarya. The cholinergic neurons in the nucleus tegmenti pedunculopontinus and the catecholaminergic neurons in A6-A7 complex display both patterns. This comparative study of three transmitter systems in the baboon suggests that the cholinergic as well as the catecholaminergic neurons that give rise to ascending telencephalic and dorsal diencephalic projections undergo phylogenetic development in terms of cell number and nuclear volume.

Acetylcholinesterase↗

[The effects of progestogens on a human endometrial cancer cell line Ishikawa and a human breast cancer cell line MCF-7].

The effects of Medroxyprogesterone acetate (MPA) and progesterone (P) on DNA and RNA contents of a human endometrial cancer cell line (Ishikawa) and a human breast cancer cell line (MCF-7) were studied using Flow cytometry. The results were as follows. MPA and P at a high dose of 10(-5) M inhibited their cell cycle progression through the G1 phase or G1-S phase boundary and showed a decrease in the number of cells which underwent DNA synthesis and mitosis. P at a low dose of 10(-7) M showed the lengthening of cell cycle time in the S phase. MPA at 10(-7) M had an inhibitory effect on the cell cycle progression of Ishikawa cells similar to that of a high dose of MPA whereas, in the case of MCF-7 cells, it showed a lengthening of duration in the S phase. Therefore, the dose-responsibility of these cells to MPA were shown to be different. A high dose of MPA and P showed a decrease in the cytoplasmic and nuclear RNA contents. A low dose of MPA and P had no marked effect on the RNA contents. From these results, it was clarified that MPA, especially at a high dose, could substantially inhibit RNA synthesis and DNA synthesis with a delay of the cell cycle progression in hormone responsive cancer cells.

Breast Neoplasms↗

Cardiovascular profile of Bay K 8644, a presumed calcium channel activator, in the dog.

Bay k 8644, although belonging to dihydropyridines, has been reported to exert effects directionally opposite to those of dihydropyridine calcium channel blockers such as nifedipine. The present experiments were carried out to elucidate whether this is indeed true. All experiments were done on isolated, blood-perfused dog-heart preparations described below, and Bay k 8644 was administered intra-arterially. In sinoatrial (SA) node preparations Bay k 8644 increased sinus rate by about 37% of the basal value at the highest dose (10 micrograms). In atrioventricular (AV) node preparations Bay k 8644 decreased AV conduction time by accelerating AV nodal but not intraventricular conduction. However, the decrease in AV conduction time remained at about 10 ms (about 7.8% of the basal value) even at the highest dose (10 micrograms). In papillary muscle preparations driven at a fixed rate of 120 stimuli/min Bay k 8644 increased the force of contraction by about 100% of the basal value at the highest dose (10 micrograms). In spontaneously beating papillary muscle preparations Bay k 8644 failed to increase the rate of automaticity although it increased the force of contraction. In all preparations Bay k 8644 decreased (coronary) blood flow down to about 20% of the basal value at the highest dose (10 micrograms). The positive chronotropic and dromotropic effects of Bay k 8644 reached respective peaks nearly at the same time as its vasoconstrictor effect, whereas its positive inotropic effect reached a peak after the vasoconstrictor effect had nearly worn off.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Nicardipine releases sustained coronary arterial constriction induced by acetylcholine in the rhesus monkey.

In five rhesus monkeys (Macaca mulatta) the vascular bed of the left anterior descending coronary artery (LAD) was perfused at constant pressure with autologous blood. Nicardipine (1-30 micrograms), a dihydropyridine calcium antagonist when injected into the LAD, increased LAD flow without producing significant changes in other cardiohemodynamic variables. With continuous infusions of acetylcholine into the LAD, the flow decreased by about 34% of the basal value. Under these conditions, intra-LAD nicardipine produced an increase in LAD flow almost to the same extent as in the control. The effects of nicardipine were qualitatively similar to those of other calcium antagonists observed in previous experiments and indicate that nicardipine would be useful as an antianginal drug.

Acetylcholine↗

Improvement by denopamine (TA-064) of pentobarbital-induced cardiac failure in the dog heart-lung preparation.

The efficacy of denopamine, an orally active beta 1-adrenoceptor agonist, in improving cardiac failure was assessed in dog heart-lung preparations. Cardiac functions depressed by pentobarbital (118 +/- 28 mg; mean value +/- SD) such that cardiac output and maximum rate of rise of left ventricular pressure (LV dP/dt max) had been reduced by about 35% and 26% of the respective controls were improved by denopamine (10-300 micrograms) in a dose-dependent manner. With 100 micrograms denopamine, almost complete restoration of cardiac performance was attained, associated with a slight increase in heart rate. No arrhythmias were induced by these doses of denopamine. The results warrant clinical trials of denopamine in the treatment of cardiac failure.

Animals↗

Identification of heterogeneous and microheterogeneous subunits of glutathione S-transferase in rat liver cytosol.

Subunits of multiple molecular forms of dimeric glutathione S-transferase in rat liver cytosol were analyzed by two-dimensional gel electrophoresis (isoelectric focusing/sodium dodecyl sulfate-electrophoresis) followed by staining with Coomassie blue dye. The five subunits, Ya, Yb, Yb', Yc, and Yp (Mr's 26,500, 27,500, 27,500, 28,500, and 26,000, respectively) of seven molecular forms, A2, AC, C2, B2, BL, L2, and GST-P, were identified by comparison of molecular weights and pI values with those of purified molecular forms and by immunoadsorption of the molecular forms in the cytosol as well as those synthesized in vitro using antibodies against the seven forms. Yp is the subunit of placental glutathione S-transferase, GST-P (YpYp), which is markedly increased in carcinogen-treated rat livers [A. Kitahara et al. (1984) Cancer Res. 44, 2698-2703; K. Satoh et al. (1985) Proc. Natl. Acad. Sci. USA 82, 3964-3968]. Microheterogeneity was detectable within Yb, Yb', and Yp subunits, the different forms, termed Yb1, Yb2, Yb'1, Yb'2, and Yp1, Yp2, being similar in size but differing by approx. 0.3 pI unit within each subunit. These microheterogeneous forms were also detectable in the polypeptides translated in vitro in a rabbit reticulocyte lysate translation system from liver poly(A)-containing RNAs, suggesting that they are translatable from distinct mRNAs.

Animals↗

Effects of insecticidal carbamates on brain acetylcholine content, acetylcholinesterase activity and behavior in mice.

Mice showed no toxic signs after a single injection of o-sec-butylphenyl methylcarbamate (BPMC, 10 mg/kg) or 2-isopropoxyphenyl-N-methylcarbamate (propoxur, 2 mg/kg). Each dose of BPMC or propoxur caused an increase in acetylcholine content and a decrease in acetylcholinesterase activity in the forebrain of mice at 10 min, followed by an almost complete recovery in the content at 60 min. Spontaneous motor activity was depressed 10 min after and recovered 60 min after, injection of BPMC or propoxur. Neither rotarod performance nor rectal temperature showed any change after injection of BPMC or propoxur. Spontaneous motor activity may therefore be a simple method for assessing small changes in the cholinergic system.

Acetylcholine↗