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Biomedical subjects

R Ishida

Publications and source records attributed to R Ishida.

At least 109 records · Page 6Linked to original sources
PubMed1989

Effects of mafoprazine, a phenylpiperazine derivative, on the central dopaminergic system.

The effects of mafoprazine, a new phenylpiperazine derivative, on the central dopaminergic system were studied. Mafoprazine, like chlorpromazine and haloperidol, reduced the apomorphine-induced cage-climbing behavior in mice, emesis in dogs and stereotyped behavior in monkeys; methamphetamine-induced hyperlocomotion and group toxicity in mice; and agitation in rats. Mafoprazine inhibited the unilateral circling behavior induced by methamphetamine and apomorphine in rats with 6-hydroxydopamine-induced lesions in the unilateral nigrostriatal neuronal tract. The potency of mafoprazine in these experiments was almost equal to that of chlorpromazine and about one-tenth that of haloperidol. The cataleptogenic activity of mafoprazine was lower than those of chlorpromazine and haloperidol. Mafoprazine potentiated clonidine-induced hypothermia. These results suggest that mafoprazine has a relatively selective postsynaptic dopamine D2-receptor blocking action in the nucleus accumbens compared with chlorpromazine and haloperidol and suggest that mafoprazine also has alpha 2-adrenoceptor-stimulating actions.

Aggression↗
PubMed1989

Effects of afloqualone on vestibular nystagmus and the lateral vestibular nucleus.

To clarify the antivertiginous effect of afloqualone, an antispastic drug, we examined its action on the vestibular nervous system in cats. The results suggest that afloqualone inhibits vestibular nystagmus probably due to both inhibition of selective polysynaptic transmission and enhancement of the effects of GABA and glycine in the lateral vestibular nucleus (LVN), and its GABA-enhancing effect is thought to be attributable to the increased sensitivity of GABA receptors of the LVN neuron site.

Acetylcholine↗
PubMed1989

[Comparing development with physical fitness, motor ability, and health of children among various living environment].

This study had the purpose to compare with development of fitness, motor ability and health among various living environments of the sea-side, the urban, and the mountain districts, where were situated at Nadachi town on the suburbs of Niigata Prefecture. Five hundred thirty-five children (aged 4-15 yrs) were measured at the kindergarten, the fundamental school, and the junior high school. Measuring items of the physique were the height, the weight, the chest circumference, the sitting height, and the foot area. Physical fitness tests were the muscular grip-strength, the lung vital capacity, the closed-eye single-leg balance, the dipping time of the upper extremity, the vertical jump, the standing trunk flexibility, the endurance run, and pull-up. And, motor ability tests were the finger tapping, 5m shuttle run, 50m dash, and the ball throwing. As items of health inspection, the blood pressure (systolic and diasystolic) and the visual ability were adopted. As results of this study, following data were obtained; 1) At the sea-side environment, development of the muscle power, the respiratory function, and the physique were showed much faster rate of growth at the childhood than that of the other ones, significantly (P less than 0.01). 2) At the mountain environment, the arch-bend of the foot print only were appeared larger areas than that of the other ones, significantly (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

[Clinical survey of caries incidence in children with cleft lip and palate].

The caries incidence was clinically examined in 119 children with cleft lip and palate (CLP; 65 male and 54 female; 2 to 14 years of age). At the lower age, the CLP children had more dental caries in the upper teeth than normal children, and, the caries prevalence became higher, with the increase in the age. In both primary and permanent dentitions, the CLP children showed an extremely high caries incidence in the upper anterior teeth, which was related to the presence of cleft. The characteristic oral structures of CLP patients; such as abnormalities of tooth position and axis, the presence of scars, and the absence of vestibular oris, increased the area on the tooth surfaces which afforded the protection from the self-cleaning activity in the mouth, and consequently induced high caries prevalence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Cross-resistance of novobiocin-resistant BHK cell line to topoisomerase II inhibitors.

A novobiocin-resistant BHK cell line, designated as NovrA2, was found to exhibit cross-resistance to other topoisomerase II inhibitors such as 4'-dimethylepipodophyllotoxin-4-(4,6-O-ethylidine-beta-D-glu copyranoside) (VP-16), adriamycin, and 4'-(9-acridinyl-amino)methanesulfon-m-anisidide (m-AMSA), and also to different types of drugs such as vinblastine and arabinocytidine. Nalidixic acid-resistant cells (A2Nalr) of the NovrA2 cell line were phenotypically reverted to novobiocin sensitivity like wild-type cells and were also partially reverted to sensitivity to VP-16 and adriamycin, but not to vinblastine and arabinocytidine. When VP-16 was added to cell culture, the drug-induced DNA strand breaks were much fewer in NovrA2 cells than in BHK cells. This reduced level of strand breaks in NovrA2 cells was not due to reduced drug uptake, because the two cell lines accumulated similar levels of radiolabeled VP-16. VP-16 also induced fewer DNA breaks in isolated nuclei of NovrA2 cells than in those of BHK cells. There was no significant difference in the VP-16-induced DNA cleavage activities of partially purified topoisomerase II from BHK and Novr cells. These results show that the resistance of NovrA2 cells to various drugs is not acquired by a defense mechanism related to membrane permeability and suggest that the resistance of the NovrA2 cells to topoisomerase II inhibitors might be due in part to alteration in a topoisomerase II associated factor(s).

Amsacrine↗
PubMed1988

Increased O6-methylguanine-DNA methyltransferase activity and reduced mutability in 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2- chloroethyl)-3-nitrosourea-resistant HeLa S3 cells.

To clarify the involvement of O6-methylguanine (O6-MeG) in mutagenesis, we have been trying to isolate Mer+ cells from a HeLa S3 Mer- cell line, and to compare the mutation frequencies between the cell lines. We previously isolated the N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-resistant cells, MR10-1, from HeLa S3 Mer- cells. However, the MR10-1 cells still had only a little O6-MeG-DNA methyltransferase (MT) activity. In the present study, we have isolated two 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU)-resistant cells, ACr41 and ACr42, from the MR10-1 cells. The two ACr cells had increased MT activities. The ACr cells were also significantly more resistant to 1-(2-chloroethyl)-1-nitrosourea and slightly more resistant to MNNG than the MR10-1 cells. When the mutation frequencies were tested at the hypoxanthine-guanine phosphoribosyl transferase and ouabain loci in these cell lines, the two ACr cells were more resistant to the mutagenic effect of MNNG than the MR10-1 cells. These results show the linkage between the resistance to the cytotoxic effect of nitrosourea compounds and MT activity, and strongly support the hypothesis that O6-MeG is the main pre-mutagenic lesion induced by MNNG.

Antineoplastic Agents↗
PubMed1988

Bunitrolol metabolism and its inhibition by cimetidine.

A simple fluorometric assay method as well as a sensitive HPLC method for determination of bunitrolol, a beta-adrenoreceptor blocking drug, and its 4-hydroxylated metabolite is described. More than 90% of bunitrolol metabolized was accounted for by the formation of 4-hydroxybunitrolol in rat hepatic microsomes. Bunitrolol 4-hydroxylation required NADPH, and was inhibited by CO, proadifen and metyrapone, indicating that this reaction is mediated by cytochrome P450. This reaction was also inhibited by cimetidine competitively, and the inhibition constant, Ki, was 40 +/- 11.5 microM (mean +/- s.e. n = 3).

Animals↗
PubMed1988

Neurochemical study of mafoprazine, a new phenylpiperazine derivative.

Mafoprazine, a phenylpiperazine derivative, was neurochemically investigated in rats to determine its action mechanism. The rank order of affinity of mafoprazine for neuronal receptors was D2 greater than or equal to alpha 1 greater than S2 greater than alpha 2 much greater than D1 greater than beta greater than mACh. The affinity of mafoprazine for D2 receptors (Ki = 10.7 nM) was 2 times higher than that of azaperone, and 6 and 16 times lower than those of chlorpromazine and haloperidol, respectively, whereas the D2 receptor selectivity [D1/D2 (Ki value ratio)] of mafoprazine was 10, 9 and 2 times higher than those of chlorpromazine, azaperone and haloperidol, respectively. The affinity of mafoprazine for alpha 2 receptors in terms of the ratio of the Ki values for D2 and alpha 2 receptors (D2/alpha 2) was 345, 26 and 3 times higher than those of haloperidol, chlorpromazine and azaperone, respectively. Mafoprazine slightly showed the inhibitory effect on dopamine-stimulated adenylate cyclase (IC50 = 52300 nM), and it had almost no affinity for beta and mACh receptors. Mafoprazine significantly increased dopamine metabolites in the corpus striatum and nucleus accumbens, although to lesser extents as compared with azaperone and chlorpromazine. These results suggest that mafoprazine probably manifests its antipsychotic action mainly through D2 receptor blocking activity and alpha-adrenergic activity (alpha 1 receptor blocking activity and alpha 2 receptor stimulating activity).

Adenylyl Cyclases↗
PubMed1988

A behavioral pharmacological study of mafoprazine, a new phenylpiperazine derivative.

Behavioral pharmacological studies on mafoprazine, a new drug for the prevention of aggressive behavior, were performed to compare its effects with those of an existing drug, azaperone (Stresnil). The acute toxicity of mafoprazine in mice was slightly stronger than that of azaperone. Mafoprazine showed the following effects (at 0.2 to 2.0 mg/kg, s.c.): a decrease in spontaneous motor activity, prolongation of the duration of pentobarbital anesthesia, inhibition of long-term isolation-induced aggressive behavior, inhibition of olfactory bulbectomy-induced hyperemotionality and muricide behavior in mice and rats, and a marked taming and tranquilizing effect on aggressive behavior in dogs. These effects of mafoprazine were qualitatively the same as those of azaperone. Mafoprazine showed cataleptogenicity in rats at 5 mg/kg, s.c. or more and motor incoordination in rats at 0.2 mg/kg, s.c. or more. In the experiment on operant behavior in rats, the effect of mafoprazine on differential reinforcement of the low rate (DRL) response was almost the same as those of azaperone and chlorpromazine. These results indicate that mafoprazine has substantially the same psychotropic effect as azaperone, while the former has a weaker action on the extrapyramidal system than the latter, suggesting that mafoprazine could be used as a unique aggression-inhibiting drug.

Aggression↗
PubMed1987

Blockade of cholinergic receptors by an irreversible antagonist, propylbenzilylcholine mustard (PrBCM), in the rat cerebral cortex causes deficits in passive avoidance learning.

Studies were made on the effects of blockade of muscarinic acetylcholine (mACh) receptors in the rat cerebral cortex on learning and memory assessed by performance of a step-through passive avoidance task. Bilateral injection of propylbenzilylcholine mustard (PrBCM) into both the frontal and parietal cortex at doses of 2.25 X 4 to 22.5 X 4 micrograms decreased mACh receptors dose-dependently, as assessed by [3H]quinuclidinyl benzilate binding studies. When the training trial of a step-through passive avoidance task was performed 24 h after injection of 7.5 X 4 to 22.5 X 4 micrograms PrBCM into the frontal and parietal cortex, and then a retention test was made 24 h after the training trial, the treated rats showed shorter latencies than controls. In contrast, injection of PrBCM into the occipital cortex had no significant effect on performance in the test. These results confirm the notion that cholinergic neurotransmission in the cerebral cortex, especially the frontoparietal cortex, is important in learning and memory. The effects of injection of PrBCM (22.5 X 4 micrograms) into the frontoparietal cortex on 3 postulated phases of the learning and memory process (i.e. registration, retention and recall) were also examined. When PrBCM was injected 24 h before the training trial, no retention of the task was observed 14 days after the training trial. However, when PrBCM was injected 24 h after the training trial, retention of the task 14 days after the training trial was not affected. When PrBCM was injected 3-24 h after the initial training trial, the latencies in the retention test examined 24 h later were shorter than those of control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Isolation and characterization of novobiocin-resistant BHK cells.

We isolated two novobiocin-resistant mutants which were stable and approximately three and four times more resistant than the parent cells to novobiocin. Both mutants (Novr A2, Novr A41) were more sensitive than the wild-type cells to nalidixic acid, and cold sensitive for cell growth. When we isolated derivatives of Novr A2 and Novr A41 cells which are resistant to nalidixic acid, those are found to be phenotypically reverted to novobiocin sensitivity like wild-type cells, thereby suggesting the relationship between the targets for novobiocin and for nalidixic acid. But the cold sensitivity did not always revert to wild type, with accompanying resistance to nalidixic acid. The DNA and RNA syntheses of Novr mutants were more resistant to novobiocin but more sensitive to nalidixic acid, than those of wild-type cells. However, in vitro assays of wild-type and Novr cell extracts were unable to demonstrate any differences in the sensitivity of topoisomerase II activity to inhibition by novobiocin. While the targets of novobiocin and nalidixic acid show a mutual interaction in vivo and play a role in DNA replication and transcription, our results suggest that these targets are probably not topoisomerase II.

Animals↗
PubMed1987

N-methyl-N'-nitro-N-nitrosoguanidine-resistant HeLa S3 cells still have little O6-methylguanine-DNA methyltransferase activity and are hypermutable by alkylating agents.

To clarify the involvement of O6-methylguanine (O6-MeG) in mutagenesis, we isolated N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-resistant cells, MR10-1 from HeLa S3 mer- cells. MR10-1 cells were 40 times more resistant to MNNG than the parental cells. MR10-1 cells were also significantly more resistant to N-methyl-N-nitrosourea and slightly more resistant to methyl methanesulfonate and dimethyl sulfate than parental cells. However, we found that MR10-1 cells had still little O6-MeG-DNA methyltransferase activity and were sensitive to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl- 3-(2-chloroethyl)-3-nitrosourea hydrochloride, like HeLa mer- cells, thereby showing that MR10-1 cells are still mer-. When induced 6-thioguanine (6TG)-resistant colonies were plotted as a function of the corresponding percentage survival, the resistant colonies of MR10-1 cells were induced much more frequently than in the case of HeLa mer- cells. However, induction of 6TG-resistant cells in both cell lines did not differ significantly in terms of mutant cells per 0.1 microM MNNG. On the contrary, MR10-1 cells (mer-) and two HeLa S3 mer+ cells lines differed in the induction of mutation as a function of MNNG concentration. The HeLa mer+ cell lines were not mutable, while MR10-1 cells were highly mutable. These above results clearly show that the HeLa mer- cell has at least two defects in the repair of the alkylated adducts which are related to cell killing and mutation, and also suggest that O6-MeG is involved in the induction of mutation.

Alkylating Agents↗
PubMed1986

[Behavioral pharmacological properties of nicergoline. Effects on gross-behavior in rats and monkeys and on DRL response, CER, and CAR in rats].

Whether nicergoline has psychotropic-like pharmacological properties was examined through the gross-behavioral and operant behavioral observations in rats and monkeys. In gross-behavioral observations, slight decrement of spontaneous motor activity, lying on the abdomen and relaxation of abdominal tone were observed in rats when nicergoline was administered intravenously (1 mg/kg or more) and intraperitoneally (4 mg/kg or more). However, when it was administered orally, slight decrement of spontaneous motor activity was observed only at large doses of 32 and 128 mg/kg. In monkeys, nicergoline produced decrement of spontaneous motor activity, palpebral ptosis, and lacrimation when administered intraperitoneally at doses of 1 mg/kg or more. Under a differential reinforcement of low rate (DRL) schedule for food reinforcement in rats, nicergoline depressed the response at 4 mg/kg, i.p., or 128 mg/kg, orally. In conditioned emotional response (CER), nicergoline had no effect on the responses during both the alarm and safe periods at doses of 0.25, 1, and 4 mg/kg, i.p., or 8, 32, and 128 mg/kg, p.o. In Sidman continuous avoidance response (CAR), nicergoline (0.25, 1, and 4 mg/kg, i.p., or 8, 32, and 128 mg/kg, p.o.) slightly depressed the response and increased the total shock. These results were compared with those of chlorpromazine, chlordiazepoxide, pentobarbital, and methamphetamine and the following conclusion was drawn: Inhibitory effects of nicergoline on gross and operant behaviors seem to be non-specific, and its behavioral pharmacological properties are qualitatively different from those of anti-psychotics, anti-anxietics, hypnotics, and stimulants.

Animals↗
PubMed1985

Effect of vitamin K3 on the first-pass elimination of propranolol in the rat.

The effect of vitamin K3, which inhibits electron transfer from NADPH to cytochrome P-450 via cytochrome c reductase, on the metabolism of propranolol was studied in the rat in vitro and in vivo. For in vitro experiments using rat liver microsomes, the metabolism of propranolol was inhibited by vitamin K3. For in vivo experiments, the area under the blood concentration-time curve and the maximum concentration of propranolol were markedly increased following intraportal infusion of propranolol with vitamin K3, but intraportal administration of vitamin K3 had little effect on propranolol kinetics when propranolol was infused intravenously. Thus, it was concluded that vitamin K3 inhibited the first-pass metabolism of propranolol.

Animals↗
PubMed1985

Caffeine alone causes DNA damage in Chinese hamster ovary cells.

Caffeine has been shown to enhance the lethal effect of DNA-damaging agents in mammalian cells, and the potentiation by caffeine of this effect is generally interpreted as the result of inhibition by caffeine of the repair of damaged DNA. However, the mechanism by which caffeine enhances the lethal effect of DNA-damaging agents has not yet been elucidated. During studies on the effect of caffeine on DNA repair, we found by alkaline elution analysis that caffeine alone produced DNA strand breaks or alkali labile sites in Chinese hamster ovary cells. The amount of DNA breakage or alkali labile sites depended on the concentration of caffeine. We propose that DNA breakage induced by caffeine may be involved in the enhancement of the lethal effect of DNA-damaging agents.

Animals↗