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Biomedical subjects

S Ueki

Publications and source records attributed to S Ueki.

At least 181 records · Page 10Linked to original sources

[Second-look operation for childhood solid malignancy].

Forty-four cases with childhood solid malignancy during the period from 1973 to 1982, were analysed. 11 cases underwent second-look operation, including 4 neuroblastomas, 4 hepatoblastomas, 1 malignant teratoma, 1 nephroblastoma, and 1 rhabdomyosarcoma. Two cases of hepatoblastoma in second-look operation are surviving over two years with no evidence of disease, and one case survived 5 years 8 months. For one patient of initially unresectable neuroblastoma, second-look operation was successfully performed by complete resection followed by paraortic-lymphonode dissection. In two cases of Wilms' tumor and malignant teratoma, second-look operations were performed for the purpose of treatment decision after radical operation. In the unresectable tumors or recurrent tumors or metastatic lesions, complete cure can be expected by aggressive surgical approach and combination chemotherapy followed by second-or third-look operation.

Antineoplastic Combined Chemotherapy Protocols↗

[Behavioral and electroencephalographic study of 7-chloro-1-methyl-5-phenyl-1 H-1,5-benzodiazepine-2,4-(3H,5H)-dione (clobazam)].

Behavioral and electroencephalographic effects of clobazam (CBZ), a 1, 5 benzodiazepine, were investigated in mice, rats and rabbits and compared with the effects of diazepam (DZP) and chlordiazepoxide (CDP). In EEG studies of rabbits, CBZ, DZP and CDP at doses of 2-10 mg/kg, i.v., caused a drowsy pattern, i.e., high voltage slow waves in the frontal cortex and the desynchronization of hippocampal theta wave. EEG arousal responses induced not only by auditory stimulation but also by electric stimulation of the mesencephalic reticular formation were inhibited by CBZ; CBZ was less potent than DZP, but more potent than CDP. On hypothalamic self-stimulation behavior of rats, low rate responses induced by low current brain stimulation, VI or DRL procedure were increased by oral administration of the three drugs. CBZ was less potent than DZP in the above respondings, but the same potency as CDP in VI or DRL responding and more potent in low rate responding induced by low current stimulation. The preventive effect of CBZ on MES convulsion in mice was less potent than DZP, but 2.5 times as potent as CDP. The preventive effect of CBZ was 1.3 times as potent as DZP and 2.5 times as potent as CDP. CBZ reduced the hyperemotionality of olfactory bulbectomized rats, and this effect was less than DZP in suppressing muricide. The muscle relaxant effect of CBZ in inclined screen and rotarod tests of mice was less than that of DZP. CBZ was 2.2 times as potent as CDP in potentiating thiopental sleep in mice, but less than DZP. These results indicate that CBZ is qualitatively similar to 1, 4 benzodiazepines, DZP and CDP, and is more potent than CDP, but less potent than DZP.

Animals↗

The mammillary body is a potential site of antianxiety action of benzodiazepines.

The present study was designed to examine the anticonflict action of benzodiazepines injected into the mammillary body (MB) using the rat conflict-punishment procedure. Diazepam 20 micrograms/microliters, chlordiazepoxide 60 micrograms/microliters and midazolam 30 micrograms/microliters, bilaterally injected into the MB, produced a significant increase in the punished responses without changes in the unpunished responses. These findings have demonstrated for the first time that the MB could be a potential site of antianxiety action of benzodiazepines.

Animals↗

Changes in amygdaloid afterdischarges and kindling effect following olfactory bulbectomy in the rat.

Changes in the thresholds for afterdischarges and the formation of kindling effect in the medial amygdala following olfactory bulbectomy were investigated in the rat with chronic electrode implants. The threshold for afterdischarges in the amygdala of the olfactory bulbectomized rat (OB rat) was significantly decreased on day 4 after olfactory bulbectomy, however, no significant difference was found between OB and sham operated rats on days 7, 14 and 21 since the threshold in the sham group was also decreased at these periods after the surgery. The formation of kindling effect was remarkably accelerated in the OB rats. In this case, the number of days required to reach the stage 1 (Racine's classification) was significantly shortened. These results suggest that the activity of the medial amygdaloid nucleus is increased following olfactory bulbectomy.

Aggression↗

Differential effects of medial, central and basolateral amygdaloid lesions on four models of experimentally-induced aggression in rats.

To clarify whether various nuclei of the amygdaloid complex play different roles in aggressive behavior including muricide, 4 types of aggression were experimentally induced in rats. These include olfactory bulbectomy (OB rats), midbrain raphe lesions (Raphe rats), administration of delta 9-tetrahydrocannabinol (THC rats) and long-term isolation (Iso rats). Rats which exhibited muricide following these treatments were subjected to bilateral lesions of either the medial (AME), central (ACE) or basolateral (ABL) amygdaloid nuclei. Both muricide and hyperemotionality in the OB rat were markedly inhibited by AME lesions. Those of the Iso and THC rats were moderately inhibited. However, in the Raphe rat, aggressive behavior was not inhibited by AME lesions. Furthermore, ACE or ABL lesions caused no significant changes in all 4 models of aggression. These results suggest that the AME plays a facilitatory role in aggression of OB, Iso and THC rats, but aggression in Raphe rat is independent of amygdaloid activity.

Aggression↗

Effects of medial amygdaloid lesions on the initiation and the maintenance of muricide in olfactory bulbectomized rats.

In order to elucidate the role of medial amygdala on the initiation and the maintenance of muricide following olfactory bulb lesions, bilateral medial amygdaloid lesions were performed after, prior to, or simultaneously with olfactory bulb lesions. Both the initiation and the maintenance of muricide following olfactory bulb lesions were suppressed by amygdaloid lesions, and this result suggests that the medial amygdala plays a facilitatory role in both the initiation and the maintenance of muricide in olfactory bulbectomized rats.

Aggression↗

Effects of locus coeruleus stimulation on muricide in olfactory bulbectomized and raphe lesioned rats.

In order to elucidate the role of central monoamines in muricide of the rat, the effects of electrical stimulation of the locus coeruleus (LC) were investigated on two types of muricide induced by olfactory bulbectomy (OB rats) and midbrain raphe lesions (raphe rats). Muricide was inhibited in 71.4% of the OB rats by bilateral LC stimulation and in 26.7% by unilateral stimulation. Even in the rat in which muricide was not inhibited following LC stimulation, muricide was almost invariably suppressed by LC stimulation after pretreatment with pargyline. The antimuricidal effect of LC stimulation was partially blocked by administration of propranolol, but not by phenoxybenzamine. In contrast, muricide was inhibited by bilateral LC stimulation in 44.4% of the raphe rats, but this effect was not potentiated by pretreatment with pargyline. On the other hand, muricide was not significantly inhibited by either dorsal raphe or medial raphe stimulation in any OB rats. These results suggest that noradrenaline plays a more important role in inhibiting muricide in OB rats than in raphe rats.

Aggression↗

[Behavioral effects of flutoprazepam (KB-509) and its metabolites].

The behavioral effects of KB-509 and its metabolites were investigated and compared with those of diazepam in mice and rats. The locomotor activity of mice measured by an Animex test was decreased with relatively large doses of KB-509 and diazepam. The anticonflict effect of KB-509 in rats was approximately as potent as that of diazepam. The lever pressing responses in the unpunished period were reduced by diazepam at a dose of 50 mg/kg p.o., while they were not affected by KB-509 even at a large dose such as 100 mg/kg p.o. KB-509 inhibited conditioned avoidance responses of the rat in a shuttle box at an extremely large dose such as 1000 mg/kg p.o. This effect of KB-509 was much less potent than that of diazepam. KB-509 was more potent than diazepam in inhibiting footshock-induced fighting behavior in mice. KB-509 and diazepam prevented maximal electroshock, pentetrazol, and strychnine induced convulsions in mice. KB-509 was more potent than diazepam in potentiating barbital anesthesia, in impairing rotarod performance, and in muscle relaxant activity measured by a traction test in mice. The pharmacological activity of desalkyl-KB-509 was more potent than that of KB-509 and that of desalkyl-3-OH-KB-509 was approximately as potent as that of KB-509. These results indicate that KB-509 possesses pharmacological properties similar to that of diazepam, and it is slightly greater in potency and is much longer in duration of action than diazepam.

Aggression↗

The role of central serotonergic mechanisms on head-twitch and backward locomotion induced by hallucinogenic drugs.

Head-twitch induced by lysergic acid diethylamide, mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM) was significantly increased by medial raphe (m-R) lesions, but dorsal raphe (d-R) lesions did not produce any changes. Hallucinogen-induced head twitch was inhibited by methysergide and tended to be increased by PCPA. These results suggest that 5-HT receptors innervated with the ascending 5-HT pathway originating in the m-R play a vital role in the manifestation of hallucinogen-induced head-twitch. That is, increase of head-twitch is ascribed to supersensitivity of 5-HT receptors. On the other hand, DOM-induced backward locomotion was inhibited by m-R or both dorsal and medial raphe lesions and methysergide, and was reversed to forward locomotion, differently from the hallucinogen-induced head-twitch. A reversion of backward locomotion was not obtained with d-R lesions or PCPA treatment.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

"Conflict" situation based on intracranial self-stimulation behavior and the effect of benzodiazepines.

Based on lateral hypothalamic self-stimulation behavior of the rat in a Skinner box, a "conflict" situation was established by combining foot shock punishment with brain stimulation. Diazepam (10-20 mg/kg, PO) caused a marked increase in the lever pressing response in the punished period without affecting the unpunished response. Bromazepam (10--20 mg/kg PO) also caused an increase in the lever pressing response in the punished period and a decrease of the punished response. These results indicate that a "conflict" situation based on self-stimulation behavior is useful for the evaluation of antianxiety action.

Animals↗

Regional changes in brain norepinephrine content in relation to mouse-killing behavior by rats.

Three separate series of experiments were conducted as follows: isolation housing, bilateral olfactory bulbectomy, and delta 9-tetrahydrocannabinol (THC) administration. All three experimental manipulations produced an increase in the incidence of mouse-killing behavior. In order to elucidate the possible neural mechanisms mediating the killing response, norepinephrine (NE) content was measured in 6 discrete areas of the brain (the cortex, striatum, amygdala, midbrain, hypothalamus, and pons plus medulla oblongata). Following isolation housing, no significant difference in NE levels of any of the brain areas was demonstrated between the aggregated and isolated rats, nor between the killer and nonkiller rats. The rats with olfactory bulbectomy exhibited high NE content in the hypothalamus as compared with the intact or sham-operated rats, but there was no significant difference between the killer and nonkiller rats. After injections of THC, NE content in both the hypothalamus and pons plus medulla oblongata was decreased independent of the manifestation of killing response. The evidence indicates no regional change in brain NE levels specific to the killing response and suggests that brain NE may not participate in the mediation of mouse-killing behavior.

Aggression↗

Pharmacological characteristics of abnormal behavior induced by harmine with special reference to tremor in mice.

Harmine, a hallucinogen with potent monoamine oxidase inhibitory properties, induced abnormal behavior, including tremor, scratching, head twitch and cage biting, in the mouse. A dose-dependent tremor was produced by all routes of administration of harmine. Although oxotremorine tremor was markedly suppressed by atropine, harmine tremor was unaffected by cholinergic drugs, remarkably inhibited by dopaminergic drugs, antidepressants and diazepam, mildly diminished by p-chlorophenylalanine, markedly augmented by 5-hydroxytryptophan and mildly increased by alpha-methyl-p-tyrosine. These findings suggest that a catecholaminergic (particularly dopaminergic) and serotonergic system imbalance plays an important role in the manifestation of harmine tremor. In view of these characteristics, harmine tremor may be useful as an effective experimental model for the evaluation of antiparkinsonism drugs, along with oxotremorine tremor because of the different mechanism of occurrence. In addition, harmine tremor appears to be useful in characterizing the properties of antidepressant drugs.

5-Hydroxytryptophan↗