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Biomedical subjects

S Otsuki

Publications and source records attributed to S Otsuki.

At least 55 records · Page 3Linked to original sources

MK-801 fails to modify the effect of methamphetamine on dopamine release in the rat striatum.

The effect of MK-801 at a dose of 0.5 mg kg-1, i.p., on methamphetamine-induced (MAP; 4 mg kg-1, i.p.) dopamine (DA) release was examined in the striatum of freely moving rats using an in-vivo microdialysis method. Combined treatment of MK-801 with MAP did not modify the MAP-induced increase in extracellular DA levels or the decrease in 3,4-dihydroxyphenylacetic acid levels. These findings suggest that MK-801 fails to modify the acute effect of MAP on DA release in the striatum. The blocking effect of MK-801 on the development of MAP-induced behavioral sensitization is unlikely to be mediated by DA neurons.

3,4-Dihydroxyphenylacetic Acid↗

Localization of the mRNAs for two dopamine D2 receptor isoforms in the rat brain.

Two molecular forms of the dopamine D2 receptor were generated by alternative RNA splicing. To investigate the relative distributions of the two mRNAs encoding the D2 receptor isoforms, D2(415) and D2(444), we performed in situ hybridization histochemistry in the rat brain with the two oligonucleotide probes. An insert probe complementary to an additional fragment of the D2 receptor mRNA cloned from the rat brain, and a spanning probe complementary to its contiguous sequence were used. These 48 base probes were 3'-end labeled with [35S]dATP. The brains were dissected from male SD rats and frozen in dry ice and acetone. Cryostat sections (16 microns) were collected on gelatin coated slides and stored at -20 degrees C. In situ hybridization studies were conducted with a probe concentration of 1 x 10(6) dpm/100 microliters of buffer per brain slice at 37 degrees C for 18-20 h in a humid chamber. The slides were washed, dried and exposed to tritium sensitive film for one week. The autoradiograph showed that both mRNA were present at high levels in the corpus striatum, accumbens nucleus and substantia nigra (pars compacta). Identical patterns of labeling were obtained in the rat brain using both the insert and spanning probes, although the optical densities detected with the insert probe were higher than those with the spanning probe in the corpus striatum. This suggests that both D2 receptor mRNAs are expressed similarly in each region of the rat brain and D2(444) expressed dominantly in the corpus striatum.

Animals↗

Methamphetamine-induced dopamine release in the medial frontal cortex of freely moving rats.

The effect of methamphetamine (MAP) on the efflux of endogenous dopamine (DA) in the medial frontal cortex of freely moving rats was evaluated by a microdialysis technique. The injection of MAP at 4 mg/kg, i.p., increased the extracellular levels of DA and decreased the levels of 3,4-dihydroxyphenylacetic acid significantly. Although the changes were smaller than those observed in the striatum, the direction and time course were similar. MAP increases the efflux of DA in the medial frontal cortex.

3,4-Dihydroxyphenylacetic Acid↗

Long-lasting enhancement of the membrane-associated protein kinase C activity in the hippocampal kindled rat.

We demonstrated that only membrane-associated protein kinase C (PKC) activity increased in the bilateral hippocampus (HIPP) up to 4 weeks and in the amygdala/pyriform cortex (AM/PC) at 4 weeks after the last kindled seizure. The enhancement of the membrane-associated PKC activity exceeds the increase in the protein concentration, which was observed in part. The overwhelming increase in the PKC activity should be of significance in the long-term maintenance of the kindling phenomenon.

Animals↗

An autopsy case of spinal arteriovenous malformation (Foix-Alajouanine syndrome).

An autopsy case of spinal arteriovenous malformation (AVM) was reported. The patient was a 75-year-old male and his initial neurologic symptoms were paraplegia, paresthesia below the umbilical level and urination difficulty. Subsequently night delirium and parkinsonism also appeared. The clinical and pathological findings in this case are identical with those in the spinal AVM except for Parkinson's disease. In addition, the lateral funiculus of the spinal cord in the middle thoracic segment showed pallor: Under light microscopy, the funiculus was spongiform, with a thinner wall of the myelin sheath, enlargement of the axon and the perivascular infiltration of phagocytes without plasma exudation. The changes in the lateral funiculus seemed to indicate early congestive changes.

Aged↗

Aldehyde dehydrogenase deficiency, flush patterns and prevalence of alcoholism: an interethnic comparison.

A study was performed to verify that the prevalence of alcohol abuse and dependence in Formosan aborigines differs from that of Taiwanese (Chinese Han people), using analysis of aldehyde dehydrogenase (ALDH) isozymes and flush patterns on randomly sampled 70 Atayal, 66 Paiwan, 61 Yami and 94 Taiwanese subjects were studied. The activity of an isomer of ALDH having a low Km (ALDH-I) in hair roots was analysed by isoelectric focusing assay. The subjective experience of flushing response after alcohol ingestion was assessed. Results showed that the rate of ALDH-I deficiency in Taiwanese (51.1%) was significantly higher than in aborigines, i.e., 6.4%, 3.9%, and 0% in Atayal, Paiwan, and Yami subjects, respectively. The percentage occurrence of ALDH-I deficiency and prevalence of alcohol dependence in Taiwanese and aborigines were negatively correlated. The predominant pattern of self-reported flush response after alcohol use among aborigines was of slow onset. The flush response to alcohol ingestion was examined in relation to aldehyde metabolizing enzyme. Since alcohol sensitivity is an important factor in the development and maintenance of the alcohol ingestion habit in humans, our results support the hypothesis that there is a biological basis in the different rates of alcohol abuse and dependence among different ethnic groups.

Adult↗

[A rare case of adult-onset Becker muscular dystrophy diagnosed by dystrophin staining].

Different diagnosis of Becker muscular dystrophy (MD) from limb-girdle MD mainly depends on the differences of heredity form and age at onset. However, sporadic cases with either type of MD often occur, and occasionally Becker MD can occur in adult age when limb-girdle MD commonly occurs. We reported the male sporadic case of Becker MD with the onset at 30 year old who was diagnosed by dystrophin staining. At the age of 30, he noticed mild difficulty to stand up and instability when hurrying up stairs. His weakness of lower limb-girdle gradually progressed, but he is able to walk without any support at the present age of 54, and he never showed weakness in upper limbs. Neurological and laboratory examination revealed that severe atrophy of lower limb-girdle, mild calf hypertrophy and moderate elevate of serum CK level. These history and symptoms hardly distinguish between Becker and limb-girdle MD. Immunostaining of biopsy muscle from the patient using the antiserum against synthetic peptide fragment of dystrophin revealed faint and patchy pattern, and immunoblot revealed 380 kd of abnormal size dystrophin. These dystrophin testing confirmed that this case was a rare case of Becker MD with adult-onset and mild clinical course.

Dystrophin↗

Effect of MK-801 on endogenous dopamine release in vivo.

The effect of MK-801 on striatal dopamine (DA) release was investigated by using an in vivo microdialysis technique in the freely moving rat. Systemic injection of MK-801 (0.25, 0.5, 1, 2 mg/kg, i.p.) reduced the extracellular level of DA significantly and produced no change in the level of 3,4-dihydroxyphenylacetic acid. The behavioral observation, recorded simultaneously, revealed that MK-801, with smaller doses, produced ipsilateral circling toward the side with the dialysis probe. At larger doses, MK-801 predominantly evoked ataxia. These findings indicate that the behavioral effect of MK-801 may not be mediated via the release of DA.

3,4-Dihydroxyphenylacetic Acid↗

Enhanced extracellular dopamine level may be the fundamental neuropharmacological basis of cross-behavioral sensitization between methamphetamine and cocaine--an in vivo dialysis study in freely moving rats.

Intracerebral dialysis was used to study the mechanism underlying cross-behavioral sensitization between methamphetamine (MAP) and cocaine. The challenge injection of cocaine caused a significantly greater increase in striatal perfusate dopamine (DA) levels in MAP-pretreated rats than in saline-pretreated rats. Similarly, the challenge injection of MAP caused a significantly greater increase in extracellular DA levels in cocaine-pretreated rats than in control rats. These results suggest that an enhancement in striatal DA efflux may play an important role in cross-behavioral sensitization between MAP and cocaine.

Animals↗

D-2 but not D-1 dopamine agonists produce augmented behavioral response in rats after subchronic treatment with methamphetamine or cocaine.

A study was performed to examine behavioral response to a challenge of selective dopamine D-1 and D-2 agonists in rats previously sensitized by subchronic administration of methamphetamine or cocaine. Rats in three groups received repeated injections (IP) of saline, methamphetamine (4 mg/kg/day) or cocaine (20 mg/kg/day), respectively, for 14 days. After an abstinence period of 7-13 days, all groups were challenged with either a selective D-1 agonist (SKF 38393) or D-2 agonists (quinpirole or RU 24213). The ability of SKF 38393 (6 mg/kg or 18 mg/kg) to produce grooming behavior did not differ significantly among the saline-, methamphetamine- and cocaine-treated groups. In contrast, quinpirole (1 mg/kg) and RU 24213 (3 mg/kg) produced more intense stereotypy consisting of rearing, sniffing and repetitive head movement in the two psychostimulant-treated groups than in the saline-treated group. Such augmented response to selective D-2 agonists was observed even after a 1-month abstinence period. These results suggest that the enduring behavioral sensitization induced by two pharmacologically distinct psychostimulant agents, methamphetamine and cocaine, occurs through a common neurobiological mechanism of lasting supersensitivity in postsynaptic D-2, but not D-1 dopamine receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Changes in brain thyrotropin-releasing hormone (TRH) of seizure-prone El mice.

We examined the anticonvulsant effects of DN-1417 an analog of the thyrotropin-releasing hormone (TRH) in seizure-prone El mice. Changes in both immunoreactive TRH (IR-TRH) and TRH receptor binding activity in discrete brain regions of El mice were also measured before and after sensitization and during the postictal period, and they were compared with those in the ddY mice. Intraperitoneal injection of DN-1417 with 150 and 450 mg/kg significantly increased the El mouse seizure threshold in a dose-dependent manner. IR-TRH in the hippocampus of El mice, which was significantly lower than in ddY mice, significantly increased after sensitization. During the postictal period, however, it slowly decreased again and then gradually recovered to the preconvulsive level without any change in TRH receptor binding. In the striatum of El mice, although TRH receptor binding was significantly higher than in ddY mice, it was not affected by sensitization. These findings indicate that the hippocampal TRH system may play an inhibitory role in El mouse seizures whereas the striatal TRH system may be important for its seizure susceptibility.

Animals↗

An analysis of anticonvulsant actions of GABA agonists (progabide and baclofen) in the kindling model of epilepsy.

The anticonvulsant action of progabide, an agonist of gamma-aminobutyric acid (GABA)A and GABAB receptors, was investigated in the kindling model of epilepsy in rats. Progabide shortened afterdischarge durations and attenuated the severity of the accompanying convulsive responses in previously kindled rats from the amygdala (AM), frontal cortex (FC), ventral and dorsal hippocampus (HIPP), in a dose-dependent manner. Although progabide was less effective in the dorsal HIPP kindled seizures, the efficacy was potent in AM, FC and ventral HIPP kindled seizures. On the other hand, the anticonvulsant action of baclofen, a selective agonist of GABAB receptors, was relatively weak in terms of the measurement of the afterdischarge duration of AM and HIPP kindled seizures even at toxic doses, compared with progabide. In addition, the anticonvulsant effects of progabide were partially reversed by treatment with the antagonist of benzodiazepine receptors, Ro 15-1788, whereas Ro 15-1788 administration alone did not alter AM kindled seizures. We concluded that the action of progabide may be mediated via the GABA/benzodiazepine receptor complex. These results support the hypothesis that a failure of GABAA-mediated inhibition is one of the bases of induction and generalization of seizures.

Animals↗

Comparison of the antimanic efficacy of carbamazepine and lithium carbonate by double-blind controlled study.

A multi-institutional study comparing the antimanic effect of carbamazepine (CBZ) and lithium carbonate (Li) was performed using a double-blind group comparison design in a series of 105 patients with bipolar disorders. CBZ and Li were given for four weeks using a fixed-flexible method at an equipotent dose ratio of 1:1, starting from an initial dosage of 400 mg with a maximum dosage of 1200 mg. The final global improvement rate, based on the number of cases showing moderate to marked amelioration of manic symptoms, was 62% in the CBZ group and 59% in the Li group, with no significant difference being found between the two groups. Incidence of cutaneous side-effects was significantly higher in the CBZ group. The mean daily dosage and serum level of CBZ in the fourth week were 674 +/- 239 mg and 7.3 +/- 2.4 micrograms/ml respectively; these were within the therapeutic range. The daily dose and serum level of Li, however, were 710 +/- 239 mg and 0.46 +/- 0.22 mEq/l, and the Li level seemed to be too low to compare its therapeutic effect with that of CBZ. Prior to the present study, approximately 80% of the patients in both groups had been receiving antipsychotic medication, equivalent to 8.0 mg of haloperidol on average, without favorable response. This medication was maintained unchanged during treatment. While the shortcomings of the present study limit the interpretation of the data, it may be suggested that the usefulness of CBZ as a drug for the treatment of manic states is comparable to that of Li.

Adolescent↗

A case of bulbospinal muscular atrophy with chief complaint of sensory disorder in the lower extremities.

A 56-year-old man was admitted to our department with a chief complaint of lower extremity dysesthesia. He described a dull numbness below the ankle and a dull pain in the nates for the past two years. Although the numbness extended to the thigh, he did not notice any muscular weakness or atrophy. Neurological examination revealed weakness and atrophy in the face, tongue and the proximal portions of all four extremities. Deep tendon reflexes were decreased. A moderate loss of vibratory sensation was noted below the knees. Electromyography showed neurogenic changes. Muscle biopsy revealed both myogenic and neurogenic changes. Sural nerve biopsy revealed a mild reduction of myelinated fibers, particularly the large-diameter fibers. Based on these findings, a diagnosis of bulbospinal muscular atrophy (BSMA) was made. In recent years, there have been some case reports of BSMA with sensory disturbances, or merely with subclinical manifestations of a sensory disturbance. This case is included in the same category as those reports, but it is interesting to note that the sensory disturbance in the lower extremities occurred as the chief complaint of the disease.

Humans↗

Senile delirium with special reference to situational factors and recurrent delirium.

Factors initiating senile delirium were examined in 129 elderly inpatients (65 years or older). Sixty-eight patients were males and 61 females, with a mean age of 76.3 years. Delirium developed in most cases on the first two days of admission in the hospital, and the admission appeared to be a key factor precipitating delirium in about 30% of the patients. Delirium resolved or improved in 80% of the patients, but usually persisted in patients with dementia. Senile delirium tended to reappear repeatedly in patients whose episode of delirium lasted for more than 2 weeks, was associated with dementia, or had a prior history of delirium.

Aged↗

Bunina bodies in dendrites of patients with amyotrophic lateral sclerosis.

We studied the brains of two cases of amyotrophic lateral sclerosis with dementia. Bunina bodies were found in the motor neurons of cranial nerve nuclei (trigeminal, facial and hypoglossal nerves) as well as in the spinal motoneurons. They appeared mostly in the cytoplasm and occasionally in the neuronal processes. However, the present electron microscopic study disclosed clearly that Bunina bodies were present not only in the cell body but also in the dendrites. No Bunina bodies were observed in the axons. It is inferred that the Bunina bodies were degenerative products formed as a result of a protein metabolism disorder.

Amyotrophic Lateral Sclerosis↗