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Biomedical subjects

S Murase

Publications and source records attributed to S Murase.

At least 19 recordsLinked to original sources
PubMed1992

Decreased sensory responsiveness of noradrenergic neurons in the rat locus coeruleus following phencyclidine or dizocilpine (MK-801): role of NMDA antagonism.

The effects of the schizophrenomimetic compound phencyclidine (PCP) on baseline activity and sensory-evoked responses of noradrenergic locus coeruleus neurons were studied with extracellular single-cell recording techniques in the chloral hydrate-anaesthetized male albino rat. PCP dose-dependently decreased firing rate, induced a more regular firing pattern of the neurons, and decreased neuronal responses to a peripheral sensory stimulus (electrical stimulation of the hindpaw). These effects of PCP were significantly decreased by pretreatment with reserpine or yohimbine, indicating that the effects of PCP were largely indirect and mediated through noradrenaline, i.e. by inhibition of its re-uptake, resulting in stimulation of alpha 2 autoreceptors. The effects of PCP were, however, mimicked by dizocilpine (MK-801), a selective non-competitive antagonist at excitatory amino acid receptors of the N-methyl-D-aspartate (NMDA) sub-type, suggesting a role also for NMDA receptors in the suppression of sensory responsiveness of locus coeruleus neurons by PCP. In view of the purported physiological role of the locus coeruleus, this effect of PCP may well contribute to the psychotomimetic properties of the drug.

Animals↗
PubMed1992

Procedure for evaluating changes in respiratory symptoms of experimentally asthma-induced guinea pigs by a personal computer.

An automated system was developed for evaluating changes in respiratory symptoms in guinea pigs over a long period with a personal computer. The data on breathing curves obtained with a body plethysmograph were analyzed to determine respiratory rate, expiration/inspiration ratio, ventilation ratio, and other parameters. With this system, respiratory changes in guinea pigs, such as increase or decrease of respiratory rate, expiration/inspiration ratio, and ventilation ratio, and death of animals could be easily observed. Investigation of delayed respiratory response to Candida albicans in sensitized guinea pigs and of the effects of SO2 or NO2 exposures on its response was carried out using this system. Respiratory changes in delayed respiratory response were mostly increased respiration rate and succeeding expiratory prolongation being noted just before death. In the influences of SO2 or NO2 exposure on delayed respiratory response, increase of respiratory rate in NO2 and expiratory and inspiratory prolongation in SO2 were found. This system should prove useful for evaluating changes in respiratory symptoms due to toxic agents, medicines, and air pollutants in small animals.

Animals↗
PubMed1992

[Protein binding of cephems in the elderly].

The serum protein-binding of 12 representative cephems (CET, CEZ, CZX, CPZ, CZON, CPM, CDZM, CFX, CMZ, CTT, LMOX, FMOX) was assessed, using sera from young healthy subjects (mean age, 28.6 years old) and elderly healthy subjects (mean age, 69.7 years old), applying equilibrium dialysis under the same conditions in vitro. The protein-binding capacity of 12 cephems in elderly subjects was significantly less than that in young subjects, and marked increase in free drug concentration was observed in elderly subjects. This decrease in the protein binding capacity of cephems in elderly subjects was possibly caused by decreased serum albumin and change in non-esterified fatty acid constitution related to aging. As free-drug concentration participates in the appearance of effects and adverse reactions, the possibility of an enhanced pharmacological effects and increased adverse reactions of cephems due to decrease of protein binding in elderly subjects should be considered.

Adult↗
PubMed1992

Determination of the subunit contact region of aspartase.

The subunits of tetrameric enzyme aspartase from Escherichia coli and Pseudomonas fluorescens were incapable of forming hybrid tetramers, suggesting that the subunit contact regions of these two enzymes are not conserved in spite of significant homology between the total sequences of the enzymes. To locate the subunit contact region, we modified cysteine residues of the intermediate species formed during the assembly of the subunits of aspartase from E. coli. Subunits modified with N-ethylmaleimide were unable to assemble into tetramers. Further experiments showed that Cys-88 was the primary residue that was modified. The sequence flanking Cys-88 is quite different from that in the the enzyme from P. fluorescens, suggesting that this region participates in the mutual recognition of subunits.

Amino Acid Sequence↗
PubMed1991

Activation of aspartase by site-directed mutagenesis.

To elucidate the role of sulfhydryl groups in the enzymatic reaction of the aspartase from Escherichia coli, we used site-directed mutagenesis which showed that the enzyme was activated by replacement of Cys-430 with a tryptophan. This mutation produced functional alterations without appreciable structural change: The kcat values became 3-fold at pH 6.0; the Hill coefficient values became higher under both pH conditions; the dependence of enzyme activity on divalent metal ions increased; and hydroxylamine, a good substrate for the wild-type enzyme, proved a poor substrate for the mutant.

Amino Acid Sequence↗
PubMed1991

Electrophysiological evidence for axonal degeneration of locus coeruleus neurons following long-term forced running stress.

Using electrophysiological methods, a change in the density of axon terminals of locus coeruleus (LC) neurons in the cerebral cortex of rats following long-term forced running stress was examined. The stressed animals were classified into two groups based on spontaneous running activity (SRA) measured for 2 weeks after the stress treatment: 1) animals showing early restoration of SRA (poststress active rat) and 2) animals showing little or no SRA (poststress inactive rat). To quantify the density of LC axon terminals in the cerebral cortex, the percentage of LC neurons antidromically activated by cortical stimulation (projection index, P-index) was assessed. The P-indices for the cortex decreased in the poststress inactive rats. Since the threshold currents for antidromic activation were not altered by the stress treatment, the observed change was considered to reflect a change of the density of LC axon terminals rather than physiological consequences. Therefore, when animals receive a prolonged, severe stress, LC neurons in a certain group of the animals may cause axonal retraction or degeneration in the cerebral cortex.

Animals↗
PubMed1991

Arterial baroreflex inhibition by gastric distension in rats: mediation by splanchnic afferents.

Arterial baroreflexes are known to be reset during activation of defense area and somatosensory receptors-afferents. Here we report that viscerosensory activation also inhibits the baroreflexes. In chloralose-urethan-anesthetized, succinylcholine-immobilized, and artificially ventilated rats, the aortic depressor nerve was electrically stimulated while propranolol was continuously infused to elicit baroreflex hypotension (BH) and baroreflex vagal bradycardia (BVB). Hydraulic distension of the stomach with warm 0.9% NaCl solution was found to suppress BVB and BH, with a threshold intraluminal pressure at times less than 5mmHg. The gastric distension also suppressed BH in atropinized rats, suggesting that inhibition involved not only cardiac but also vascular components of baroreflexes. Bilateral splanchnectomy largely attenuated the inhibition, whereas bilateral subdiaphragmatic vagotomy had little effect. Low- as well as high-frequency stimulation of the splanchnic nerve strongly suppressed both BVB and BH, whereas only low-frequency stimulation of the subdiaphragmatic vagus inhibited baroreflexes to a slight degree. In conclusion, gastric distension suppresses BVB and BH, and this inhibition is largely mediated by afferent fibers in the splanchnic nerve. Such baroreflex inhibition may be a general consequence of mechanoreceptor activation of any visceral hollow organs because the jejunum, esophagus, and urinary bladder were all found to suppress arterial baroreflexes when distended.

Animals↗
PubMed1991

Subarachnoid dissemination of pineal germinoma 9 years after radiation therapy without local relapse--case report.

A 22-year-old female developed intracranial and spinal subarachnoid metastases 9 years after radiation therapy for a pineal germinoma. Computed tomographic scans showed no evidence of local recurrence. Cerebrospinal axis irradiation achieved total remission. Delayed subarachnoid dissemination may be caused by germinoma cells remaining dormant in the subarachnoid space, outside the radiation field.

Brain Neoplasms↗
PubMed1990

Transplantation of embryonic olive in the climbing-fiber-deprived adult rat cerebellum: synaptogenesis on host Purkinje dendritic spines by donor climbing fibers.

Synaptic formation by donor climbing fibers on the host Purkinje spines was observed in our experiments. In the adult rat cerebellum where the inferior olive and climbing fibers had been destroyed by intraperitoneal injection of 3-acetylpyridine, the medullary embryonic 14-16-day (E14-E16) tissue containing the olive was grafted. After 3 weeks, climbing-fiber-type preterminals bearing closely-packed round vesicles were found that established synaptic contacts on dendritic spines of the host Purkinje cells. Quantitative analysis indicates the increment of newly-formed climbing presynaptic terminals, the number of which was statistically significant (P less than 0.01).

Afferent Pathways↗
PubMed1990

Development of the rodent cerebellum and synaptic re-formation of donor climbing terminals on spines of the host Purkinje dendrites after chemical deafferentation.

Reinnervation of host Purkinje cells by donor climbing fibers was observed in the following experiments. Medullary primordial tissue (from E14-E16) containing the inferior olive was grafted into a host rat cerebellum, in which the inferior olivary complex and climbing fibers had been destroyed by intraperitoneal injection of 3-acetylpyridine (3-AP). After 3 weeks, immature as well as mature types of climbing fiber terminals bearing packed round vesicles were found that had established synaptic contacts on dendritic spines of the host Purkinje cells. Quantitative analysis at the ultrastructural level has been carried out. The main results are as follows. (1) The number of preterminals that formed synaptic contacts with spines of the host Purkinje dendrites in the transplanted material increased by 3.4-fold compared to the control (3-AP-treated non-grafted material). (2) The number of mature climbing-type preterminals increased from 0.3-0.9% to 5% after grafting (cf. 22% in normal brain tissue), and the number of immature climbing-type preterminals also increased from 2-10% (control) to 20% after grafting. These changes were statistically significant (P less than 0.01). (3) The number of parallel-type preterminals increased from 13% (control) to 27% after grafting, which was also statistically significant (P less than 0.01). Thus, it appears that the donor climbing fibers grow and develop to find unoccupied spines on the host Purkinje dendrites and establish synaptic contacts, and also that the host parallel fibers may generate axonal sprouts to search their new targets and ultimately to form synaptic contacts with unoccupied spines. In the process of re-modeling the brain, competition for targets is likely to occur between the two kinds of axonal processes, i.e. the donor climbing fibers and the host parallel fibers.

Animals↗
PubMed1989

Obsessive-compulsive symptoms in childhood and adolescence.

We investigated 61 patients (38 boys and 23 girls) under 18 years of age with obsessive-compulsive symptoms seen in the Department of Psychiatry, Nagoya University Hospital, from 1982 until 1986. In this period, a total of 1293 patients under 18 years of age visited the clinic. The percentage of patients with obsessive-compulsive symptoms was 5%. The earliest onset of symptoms was at age 3 years, and the average age of onset was 11.6 years. We found no particular tendency in terms of the number of siblings and the birth order of the patients. Obsessive traits were the fundamental personality traits of patients. Moreover, according to the other characteristics of personality, the patients were subdivided into schizothymic, viscous temperament, and cyclothymic. Parents of the patients were more apt than usual to have obsessive-compulsive personalities. Psychiatric disturbances and occupations were also investigated. Incidents related to school situations commonly triggered obsessive-compulsive symptoms. The most frequently noted obsessive thought was dirt phobia, and the most common compulsive behavior was washing. School refusal and violence at home were especially common as associated symptoms of obsessive-compulsive symptoms. We also describe the treatment regimen and the outcomes of the patients.

Adolescent↗
PubMed1988

Calcium-requirement and its pH dependency of lysophosphoinositide-specific phospholipase C in porcine platelet membranes.

The lysophosphoinositide-specific phospholipase C (lysoPI-PLase C) in porcine platelet membranes had an optimal pH of 9.2 and the activity at a physiological pH of 7.3 was 20% of the maximum in the absence of added divalent metals (Murase, S. et al. (1985) J. Biol. Chem. 260, 262). The activity was completely inhibited by 1 mM EGTA in the assay mixture but was restored by addition of excess Ca2+ or Mn2+, indicating that this is a metalloenzyme. However, membranes pretreated with 1 mM EGTA and washed with buffer retained full activity at a free Ca2+ concentration of 5 nM and no stimulation was observed by added Ca2+ at pH 9.2. In contrast to the results obtained at pH 9.2, addition of Ca2+ stimulated lysoPI-PLase C activity severalfold at pH 7.3, apparently by shifting down the optimal pH and broadening the pH profile. The effect of Ca2+ at pH 7.3 was to enhance Vmax with no significant change in Km value. The stimulatory effect of Ca2+ at pH 7.3 alone did not appear to be of physiological significance since millimolar concentrations of Ca2+ were necessary to reach the maximum activity. However, a shift in pH had a profound effect on the Ca2+-dependency of the activity. A rise in 2 pH units increased the apparent affinity for Ca2+ 10,000-fold. These results indicate that the alkalinization and the rise in free Ca2+ concentration known to occur in stimulated platelets could synergistically provide conditions under which the lysoPI-PLase C exerts its activity when the substrate lysoPI is generated by phospholipase A.

Animals↗
PubMed1987

Effect of antidepressant on behavior and central catecholamine of depression-model rats.

Effect of antidepressant on behavior and central catecholamine were investigated in depression-model rats produced by long-term forced running stress. Changes in the spontaneous running activity and the concentration and turnover of catecholamine were examined in non-stressed rats injected with saline and depression-model rats injected with saline, imipramine and MOD-20 (a candidate for a tetracyclic antidepressant). Running activity was significantly restored by injection of imipramine and MOD-20. In depression-model rats, the concentrations of central catecholamine increased in the cell bodies and nerve terminals of the ascending noradrenaline system, and turnover rates of the catecholamine decreased in the terminal region. The increased concentrations were returned to the non-stressed level after injection of the drugs. However, decreased turnover rates were not recovered after the injection. These results suggested that MOD-20 was a potent antidepressant and the therapeutic efficacy of antidepressants might be due to the restoration of catecholamine concentrations.

Animals↗