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Biomedical subjects

R Ishida

Publications and source records attributed to R Ishida.

At least 127 records · Page 7Linked to original sources
PubMed1985

Chromosomes of G2 arrested cells are easily analyzed by use of the 'tsBN2' mutation.

The tsBN2 cell line, a temperature sensitive (ts) mutant of the BHK21/13 cell line (Nishimoto, T. et al. Somatic Cell Genet. 4, 323-340, 1978) has a ts defect in its regulatory mechanism for the initiation of chromosome condensation, the so-called, premature chromosome condensation (PCC) being induced at a nonpermissive temperature (Nishimoto, T. et al. Cell 15, 475-483, 1978, Nishimoto, T. et al. J. Cell Physiol. 109, 299-308, 1981). Using the 'tsBN2' mutation, we analyzed chromosomes of tsBN2 cells arrested in the G2 phase with neocarzinostatin (NCS) and found considerable aberrations, such as gaps, breaks and double minutes-like fragmentation, in addition to a typical G2-chromosome (a long filamental chromosome made up of two chromatids). Our results provide evidences that the tsBN2 cell line can be used for examinations of the chromosomes of cells arrested in the G2 phase.

Animals↗
PubMed1984

Gas chromatographic--mass spectrometric determination of amitriptyline and its major metabolites in human serum.

A gas chromatographic--electron-impact ionization mass spectrometric method has been developed for the determination of amitriptyline (AMT) and its metabolites, nortriptyline (NT), 10-hydroxyamitriptyline (10-OH-AMT) and 10-hydroxynortriptyline (10-OH-NT) in human serum. The lower limit of detection was 2 ng/ml for all compounds except 5 ng/ml for 10-OH-NT. The calibration curves for AMT and 10-OH-AMT were linear up to 100 ng/ml, and up to 200 ng/ml for NT and 10-OH-NT. The accuracy of the assay in terms of coefficient of variation was less than 7%. The extraction efficiency was almost quantitative for all compounds except 60% for 10-OH-NT. Using this method, human serum samples which had been collected after oral administration of a single 50-mg dose of AMT were analyzed. Ratios of the conjugation of each metabolite were estimated, including AMT.

Amitriptyline↗
PubMed1982

Pharmacological studies on 6-amino-2-fluoromethyl-3-(O-tolyl)-4(3H)-quinazolinone (afloqualone), a new centrally acting muscle relaxant. (II) Effects on the spinal reflex potential and the rigidity.

Effects of afloqualone on mono- (MSR) and poly-synaptic reflex (PSR) potentials and alpha- and gamma-rigidities were studied in experimental animals. Afloqualone dose dependently inhibited both MSR and PSR potentials in spinalized cats though afloqualone had no inhibitory effect on the patellar reflex in cats as reported in the previous paper. Afloqualone, like tolperisone, more selectively inhibited the PSR potential than MSR potential, whereas baclofen inhibited them in reverse order. However, the selectivity towards the PSR potential was higher with afloqualone than with tolperisone. In rats and cats, afloqualone dose dependently relaxed both alpha- and gamma-rigidity when administered p.o. as well as i.v. Its 50% inhibitory dose for alpha-rigidity was 1.5-2 times larger than that for gamma-rigidity. Tolperisone also relaxed both rigidities in i.v. administration, but had little effect when given p.o. Only mephenesin relaxed the post-ischaemic spinal rigidity in cats. These results suggest that afloqualone, like other well known centrally acting muscle relaxants except for baclofen, more strongly inhibits the polysynaptic pathway than the mono-synaptic pathway of the spinal cord as well as more strongly the gamma-system than the alpha-system.

Animals↗
PubMed1982

Susceptibility of Fanconi's anemia lymphoblasts to DNA-cross-linking and alkylating agents.

In order to develop the usefulness of Fanconi's anemia (FA) lymphoblast lines for biochemical and genetic studies, we have determined their sensitivity to a variety of DNA-damaging chemicals. We have adapted a growth inhibiton protocol in which the sensitivity of a cell line is characterized by the drug concentration yielding a 50% inhibiton of growth (EC50). The DNA-cross-linking agents, mitomycin C, nitrogen mustard, melphalan, 1,3-butadiene diepoxide, cis-diaminedichloroplatinum(II), and cyclophosphamide, were all more toxic to four FA cell lines than to five normal lines. Three lines, HSC 72 (FA), 99 (FA) and 230 (FA), had EC50s that were 10 to 20 times lower than that of controls while the fourth line, HSC 62 (FA), had an intermediate EC50. Three nitrosourea compounds were also more toxic to FA cells than to controls. However, 2 normal cell lines (HSC 92 and 93) had nitrosourea EC50s 4 to 7 times lower than the other nine controls and overlapped the sensitivity of the intermediate [HSC 62 (FA)] cell line. The same 2 normal cell lines were also more sensitive than 12 other controls, including FA heterozygotes, xeroderma pigmentosum, and ataxia telangiectasis, to the monofunctional alkylating agents, ethyl methane sulfonate, methyl methane sulfonate, and N-methyl-N'-nitro-N-nitrosoguanidine. Heterogeneity was also found with FA lines. Two FA cell lines (HSC 72 and 230) had EC50s lower than all control lines while one FA line (HSC 99) had an EC50 similar to that of the resistant normal lines. FA and normal cells had nearly the same sensitivity to 4-nitroquinoline-1-oxide and bleomycin. These results demonstrate that FA lymphoblast lines are more sensitive than normal cell lines to all DNA-cross-linking agents examined. These cell lines should therefore be useful for the analysis of DNA cross-link repair and the biochemical defect in FA. We have also found an unexpected sensitivity of some FA and normal lines to monofunctional alkylating agents.

4-Nitroquinoline-1-oxide↗
PubMed1981

The synthesis of protein(s) for chromosome condensation may be regulated by a post-transcriptional mechanism.

A temperature sensitive mutant of BHK21, tsBN2, showed a premature chromosome condensation (PCC) upon the temperature shift of 40.5 degrees, even in the absence of DNA replication. The induction of PCC requires new protein synthesis, but not necessarily new RNA synthesis. Our data suggested that the messenger RNA for chromosome condensation starts to be transcribed at the beginning of S phase. At the permissive temperature (33.5 degrees), the messenger RNA for chromosome condensation translated with a very slow rate during S phase and rapidly in G2-M phase. At the nonpermissive temperature (40.5 degrees), however, those messenger RNAs were translated anytime, so that various figures of PCC appeared depending on the cell cycle. On the way of PCC induction, ribosomal RNA synthesis was inhibited at first, as expected from mitosis. Our data suggested that the synthesis of protein(s) for chromosome condensation was regulated by the post-transcriptional mechanism, in which tsBN2 might be defective, especially at the translational level.

Animals↗
PubMed1981

[Effects of afloqualone, a centrally acting muscle relaxant, on the sleep-wakefulness cycle in cats with chronically implanted electrodes (author's transl)].

The present study was carried out to elucidate whether or whether not afloqualone has a hypnotic action because of its similarity in chemical structure to methaqualone. In the sleep-wakefulness cycles during the 8-hour observation period (9:00-17:00), afloqualone increased the percentages of resting (REST) and slow wave light sleep (SWLS) stages at a dose of 25 mg/kg (p.o.), producing a moderate muscle relaxation. Even at a dose of 50 mg/kg (p.o.) where a marked muscle relaxation was produced, afloqualone had no influence on the percentage of slow wave deep sleep (SWDS) stage, though it increased the percentages of SWLS and decreased the percentages of awake (AWK), REST and fast wave sleep (FWS) stages. On the other hand, tolperisone . HCl, chlormezanone, methaqualone and pentobarbital . Na, used as the reference drugs, all increased the percentage of SWDS stage, but either decreased or had no effect on the percentages of the other four stages at pharmacologically effective doses. From these results it was concluded that afloqualone seems to be devoid of a hypnotic action and has different effects on the sleep-wakefulness cycle than those of both the hypnotics and the other muscle relaxants used.

Animals↗
PubMed1981

[Effects of afloqualone, a new centrally acting muscle relaxant, on DRL response and CER in rats (author's transl)].

In gross-behavioral observations, chlordiazepoxide, diazepam, meprobamate, and pentobarbital-Na produced excitatory behavior at 5 and 10, 1 and 2, 100 and 200, and 10 and 20 mg/kg p.o., respectively whereas afloqualone produced no excitatory behavior at doses up to 20 mg/kg p.o., these doses induce muscle relaxation and motor depression. Afloqualone depressed DRL response at 10 and 20 mg/kg p.o. Similar effects were seen with chlorpromazine (5, 10, 20 mg/kg p.o.). Chlordiazepoxide, meprobamate, and pentobarbital-Na facilitated DRL response at doses producing excitatory behavior. Methamphetamine (0.5, 1, 2 mg/kg p.o.) facilitated the response, dose-dependently. In CER, chlordiazepoxide (5, 10, 20 mg/kg p.o.), diazepam (1, 2, 5 mg/kg p.o.), and meprobamate (50, 100, 200 mg/kg p.o.) dose-dependently increased the response during the alarm period, regardless of the response during the safe period. Pentobarbital-Na (5, 10, 20 mg/kg p.o.) had much the same effect. Afloqualone slightly increased the response during the alarm period in one out of 3 rats at 5, 10, and 20 mg/kg p.o., respectively. Chlorpromazine and methamphetamine had no influence on the response during the alarm period at doses up to 20 and 2 mg/kg p.o., respectively. These results suggest that the pharmacological properties of afloqualone, as related to behavior differ from those of anti-anxiety drugs, hypnotics, and stimulants.

Animals↗
PubMed1981

[General pharmacology of 6-amino-2-fluoromethyl-3-(o-tolyl)-4(3H)-quinazolinone (afloqualone), a new centrally acting muscle relaxant. I. Effects on the central nervous system (author's transl)].

The general pharmacology of afloqualone, a new centrally acting muscle relaxant, in the CNS was examined in mice and rats and findings compared with those of other central muscle relaxants. Afloqualone showed relatively strong hexobarbital and barbital anesthesia potentiating action. Taking into account the dose ratio of anesthesia potentiating action to the muscle relaxing action, however, the potency of anesthesia potentiating action of afloqualone is lower than that of chlormezanone. At doses producing muscle relaxing action, afloqualone inhibited spontaneous motor activity, methamphetamine-induced hypermotility, pentylenetetrazol-, nicotine-, and maximum electroshock-convulsions, fighting episodes in foot-shocked mice, conditioned avoidance response in rat pole-climbing test, and acetic acid-induced writhing syndrome and lowered normal body temperature. The dose ratios of these pharmacological actions to muscle relaxing action of afloqualone, however, were larger than those of chlormezanone and mephenesin. This suggests that the central depressant activity of afloqualone is less potent and the specificity of muscle relaxing action of afloqualone is higher than those of climbing behaviour, physostigmine-induced death, serotonin-induced heat twitch, and reserpine-induced hypothermia, even at 50 mg/kg. Tolperisone showed neither muscle relaxing action nor other central actions when administered orally.

Agonistic Behavior↗
PubMed1981

[General pharmacology of 6-amino-2-fluoromethyl-3-(o-tolyl)-4(3H)-quinazolinone (afloqualone), a new centrally acting muscle relaxant. II. Effects on the peripheral system (author's transl)].

The general pharmacology of afloqualone, a new centrally acting muscle relaxant, in the peripheral system, was examined in laboratory animals and findings compared with those of some other central muscle relaxants. Afloqualone dose dependently inhibited respiration, lowered arterial blood pressure, decreased heart rate, and slightly increased femoral and renal arterial blood flow in parallel with hypotension, at doses of 1 or 2 to 20 mg/kg iv. in anesthetized cats. Afloqualone also inhibited cardiac movement in situ in anesthetized rabbits and decreased internal pressure in the urinary bladder in anesthetized cats. In in vitro experiments, afloqualone inhibited spontaneous movements of isolated rabbit atrium and ileum and isolated rat uterus at considerably high concentrations of 10(-6) g/ml or more. Oral administration of afloqualone, however, had no significant influence on respiration, the cardiovascular, digestive, and autonomic nervous systems, and urogenital organs, at doses up to 50 mg/kg except for a comparatively potent inhibitory effect on carrageenin-induced paw edema in rats. Afloqualone induced neither surface nor infiltration anesthesia.

Animals↗
PubMed1979

Studies on biologically active halogenated compounds. 1. Synthesis and central nervous system depressant activity of 2-(fluoromethyl)-3-aryl-4(3H)-quinazolinone derivatives.

Some 2-(fluoromethyl) analogues of 2-methyl-3-aryl-4-(3H)-quinazolinones have been synthesized and screened for CNS activities. It was shown that the 2-(fluoromethyl) analogues possess in general more potent CNS depressant activities and less toxicities than their parent compounds. Of particular interest were the 2-(fluoromethyl) analogues (22, 24, and 31) of methaqualone and 6-aminomethaqualone. Compound 24 was more potent in CNS depressant activity and less toxic than methaqualone. Compound 31 exhbited potent central muscle relaxing activity and markedly reduced toxicity as compared with 6-aminomethaqualone.

Animals↗
PubMed1976

[Biological fate of 3H-labeled penfluridol. (3) Correlation between concentration of 3H-penfluridol in the brain and its anti-methamphetamine activity].

The Penfluridol (PFL) is a potent and long-acting neuroleptic belonging to the diphenylbutyl piperidine series. The purpose of the present study is to investigate a correlation between the brain concentration of unchanged 3H-PFL and its neuroleptic activity in the methamphetamine-antagonism test. The experimental animal comprised adult male Wistar rats weighing about 200 g. All the rats were administered 3H-PFL orally and killed at appropriate times after administration. After killing blood samples were collected and the brain and liver were excised. The blood was extracted with 4 volumes of ethanol. The brain and the liver were homogenized in 9 volumes of ethanol. The amount of 3H-PFL in the ethanol extract was determined by thin-layer chromatography. The result showed that the drug level in the brain was relatively constant when the dose was the median effective dose (ED50) for the test at those time intervals after administration.

Animals↗
PubMed1976

[Pharmacological studies of an antipschotic agent, penfluridol. (1). The central pharmacological actions].

Neuropharmacological properties of penfluridol (TLP-607) were investigated in experimental animals and were compared with those of haloperidol and chlorpromazine. Locomotor activity of mice significantly decreased at doses of 16-32 mg/kg p.o. Like haloperidol and chlorpromazine, TLP-607 (4-16 mg/kg p.o.) demonstrated catalepsy lasting for 48-72 hr in rats. TLP-607 strongly inhibited apomorphine-induced emesis in dogs and the ED50 was 0.016 mg/kg p.o. This effect lasted for 192 hr when administered 0.04 mg/kg p.o. TLP-607 antagnonized methamphetamine-induced stereotyped behavior in rats, and the ED50 was 1.83 ng/kg p.o. TLP-607 also inhibited conditioned avoidance responses in rats, and the ED50's in the pole climbing and Sidman avoidance methods were 6.73 and 3.4 mg/kg p.o., respectively. TLP-607 neither inhibited motor coordination nor enhanced hexobarbital-induced anesthesia in mice. These results suggest that TLP-607 is a potent and long-acting antipsychotic drug which has less neurotoxic side-effects.

Agonistic Behavior↗