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Biomedical subjects

Y Asami

Publications and source records attributed to Y Asami.

50 records · Page 3Linked to original sources
PubMed1985

Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity.

Experiments were carried out to study the relationship between binding affinity to the benzodiazepine receptor and pharmacological activity, especially anti-anxiety activity, of clinically useful benzodiazepines. In the in vitro experiments, fludiazepam showed the highest affinity to the benzodiazepine receptor with 4 times more potency than that of diazepam, which paralleled the in vivo activity. Diazepam and nimetazepam also bound with high affinities as expected from their in vivo activities. On the contrary, medazepam and cloxazolam showed extremely low affinities and oxazolam showed no affinity, although they showed moderate in vivo activity. However, their metabolites were found to have both high affinity and in vivo activities. These results strongly suggest that in the case of medazepam, cloxazolam and oxazolam, their metabolites may bind to receptor sites in the brain and then elicit pharmacological action. This conclusion was supported by the fact that a good correlation between the binding affinity and the anti-anxiety activity of the tested compounds was observed.

Animals↗
PubMed1985

Molecular cloning of the cls gene responsible for cardiolipin synthesis in Escherichia coli and phenotypic consequences of its amplification.

The cls gene responsible for cardiolipin synthesis in Escherichia coli K-12 was cloned in a 5-kilobase-pair DNA fragment inserted in a mini-F vector, pML31, and then subcloned into a 2.0-kilobase-pair fragment inserted in pBR322. The initial selection of the gene was accomplished in a cls pss-1 double mutant that had lesions in both cardiolipin and phosphatidylserine synthases and required either the cls or the pss gene product for normal growth at 42 degrees C in a broth medium, NBY, supplemented with 200 mM sucrose. The cloned gene was identified as the cls gene by the recovery and amplification of both cardiolipin and cardiolipin synthase in a cls mutant as well as by the integration of a pBR322 derivative into its genetic locus at 27 min on the chromosome of a polA1 mutant. The maxicell analysis indicated that a protein of molecular weight 46,000 is the gene product. The cls gene is thus most likely the structural gene coding for cardiolipin synthase. Hybrid plasmids of high copy numbers containing the cls gene were growth inhibitory to pss-I mutants under the above selective conditions, whereas they inhibited neither the growth of pss-I mutants at 30 degrees C nor that of pss+ strains at any temperature. Amplification of cardiolipin synthase activity was observed, but was not proportional to the probable gene dosage (the enzyme activity was at most 10 times that in wild-type cells), and cardiolipin synthesis in vivo was at the maximum 1.5 times that in wild-type strains, implying the presence in E. coli cells of a mechanism that avoids cardiolipin overproduction, which is possibly disadvantageous to proper membrane functions.

Cardiolipins↗
PubMed1982

Comparative studies on the structures of the carbohydrate moieties of human fibrinogen and abnormal fibrinogen Nagoya.

Human fibrinogen contains four asparagine-linked sugar chains in one molecule. All B beta and gamma subunits obtained from both normal fibrinogen and abnormal fibrinogen Nagoya contain 1 mol each of an asparagine-linked sugar chain. The sugar chains were quantitatively liberated as radioactive oligosaccharides from the polypeptide portion by hydrazinolysis followed by N-acetylation and NaB3H4 reduction. By the combination of sequential exoglycosidase digestion and methylation analysis, the structures of the sugar chains of human fibrinogen were elucidated to be NeuAc alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 6(NeuAc alpha 2 leads to 6Gal beta 1 leads to 4GlcNac beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4GlcNAc and Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 6(NeuAc alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4GlcNAc. Neither quantitative nor qualitative differences were found between the sugar chain moieties of normal fibrinogen and fibrinogen Nagoya, indicating that the molecular basis of the abnormality in the latter may reside in its polypeptide moieties.

Asparagine↗
PubMed1980

Isozyme patterns of pyruvate kinase and differentiation of Friend leukemia cells.

The isozyme patterns of glycolytic enzymes of Friend leukemia cells (FLC) were compared with those of erythrocytes and erythroblasts. Erythrocyte-specific R types of pyruvate kinase (PK) were clearly observed in phenylhydrazine-induced mouse erythroblast, and much less amount of them was also observed in Friend leukemia cells. When FLC were induced to differentiate by hexamethylene-bisacetamide (HMBA), the R types were slightly reduced. When the induction of differentiation was inhibited by 12-O-tetradecanoylphorbol 13-acetate (TPA), the R types and M2-R hybrids rather increased. These results are reverse of those obtained when hemoglobin production is used as a marker of differentiation. Isozyme patterns of lactic dehydrogenase and aldolase did not change during differentiation of FLC induced by HMBA, and were the same as those of mouse erythroblasts and erythrocytes.

Acetamides↗
PubMed1976

[Effects of l-methyl-5-(O-fluorophenyl)-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-One (ID-540) on operant behavior in rats].

Effects of ID-540, a new benzodiazepine derivative, on operant behavior were studied and compared with those of diazepam in rats for the purpose of determining the characteristics on behavioral pharmacology. Four schedules used were as follows: Fixed interval (FI-60sec) of food reinforcement and differential food reinforcement of low rate (DRL20sec) for positively reinforced behavior, Sidman-type avoidance response for negatively reinforced behavior and conflict behavior induced by simultaneously rewarding with food and punishing with electric shock. In the experiments on FI-60sec schedule, the responses at the early stage (0 approximately 30 min after administration of the drug) were increased by both ID-540 and diazepam at lower doses (0.5 approximately 4 mg/kg p.o.), but inhibited at higher doses (8 approximately 32 mg/kg p.o.). The effect of ID-540 lasted longer than that of diazepam. In the experiments on DRL20sec schedule, neither drug accelerated the responses, but decreased the lever-press response and total number of reinforcements at higher doses (4 mg/kg or more) showing the disturbance of discrimination on time. In Sidman-type avoidance responses, ID-540 did not show any inhibitory effect, thus a neuroleptic-like effect of ID-540 was not demonstrated. In experiments on FI-60sec and Sidman-type avoidance schedules, the effect of ID-540 was not changed by a consecutive administration for 10 days. Conflict behavior is considered to resemble the anxiety states in humans, and in related experiments, ID-540 increased the lever-press response which delivered a food-pellet and an electric shock simultaneously at a dose of 0.0625 mg/kg (i.p.). Change in other behavior was not observed at this dose level. Maximum effect of ID-540 was observed at a dose of 0.5 mg/kg (i.p.). Maximum effect of diazepam on conflict behavior was seen at a dose of 4 mg/kg (i.p.). The potency of ID-540 on conflict behavior was estimated to be about 8 times that of diazepam.

Animals↗
PubMed1975

The synthesis and pharmacology of a novel benzodiazepine derivative, 1-(beta-methylsulfonylethyl)-5-(o-fluorophenyl)-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-one (ID-622).

The pharmacological profiles of a new benzodiazepine derivative, 1-(beta-methylsulfonylethyl)-5-(o-fluorophenyl)-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-one (ID-622), were shown. In anti-convulsant test, ID-622 was more potent than diazepam and medazepam when tested with pentylenetetrazol or bemegride, but was less potent than diazepam tested with strychnine or MES in mice. Taming effects of ID-622 were more potent than diazepam in both electroshock- and isolation-induced fighting mice tests, but were less potent in both septal rats and O.B. rats tests. ID-622 had only a weak influence on the spontaneous locomotor activity, and did not cause the righting reflex loss. In EEG, ID-622 increased fast activity and depressed hippocampal I-waves and amygdala after-discharge in cats. Acute toxicity of ID-622 was very low.

Animals↗
PubMedDate not supplied

New 4-hydroxypyridine and 4-hydroxyquinoline derivatives as inhibitors of NADH-ubiquinone reductase in the respiratory chain.

Many derivatives of 2,3-dimethoxy-4-hydroxypyridine, which were designed from examination of the structure-activity relationship of piericidins, were tested for inhibition of NADH-UQ reductase. The lipophilic side chain of those compounds was indicated to be a key part for activity and its optimal length was conjectured. By the use of two different phases of assay material, intact mitochondria and submitochondria, the size of a membrane effect was shown to depend on the structure of the side chain. 4-Hydroxyquinoline derivatives were also tested for an analogous role in relation to the electron transport function of menaquinone, and they were proven to be inhibitors of NADH-UQ reductase as good as the pyridine derivatives.

Animals↗
PubMedDate not supplied

A suggested method for mixing direct filling restorative gallium alloy.

Good wettability is one of the desirable physical properties of mercury-free gallium-based alloys (Gallium Alloy GF). However, wettability, while providing good adhesion to the cavity wall, has the adverse effect of causing stickiness to the inside of the capsule during mixing, and also to the metal hand instruments used for packing. To control this stickiness the alloy mixture was treated with a small amount of alcohol using two different methods. In both groups (alcohol-added and alcohol-treated groups), 5, 10, or 15 microliters of alcohol was added. However, for the alcohol-treated group, the alcohol was shaken from the mixture. In both groups, remarkable improvement was seen in their handling properties, for the alloy mixture did not adhere to the inside of the capsule and was easily taken out as one mass. Compressive strength, tensile strength, and creep were tested in the alcohol-added/-treated groups, and compared with those of a control (conventionally mixed gallium alloy) and a high-copper amalgam (Spherical-D). All tests were done according to ISO 1559 (International Organization for Standardization, 1986), and the results were analyzed using one-way ANOVA (Duncan, P < 0.05). Surface microhardness (KHN) and dimensional change during hardening were evaluated according to ISO 1559 and compared to the control results. In mixing Gallium Alloy GF, an addition of less than 5 microliters of alcohol had the effect of preventing the alloy mixture from sticking to the inside of the capsule and remarkably enhanced the handling properties. This suggested mixing technique did not alter either the mechanical properties tested for this material or the desirable dimensional expansion that occurs during hardening.

Alloys↗