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Biomedical subjects

M Ishida

Publications and source records attributed to M Ishida.

At least 235 records · Page 13Linked to original sources

Actions of acromelic acid on nervous system L-glutamate receptors.

Acromelic acid, a naturally occurring kainoid, isolated from the mushroom Clitocybe acromelalga, is a weak displacer of [3H]L-glutamate binding to cockroach (Periplaneta americana) nerve cord membranes. Acromelic acid (1 mM) displaces approximately 60% of specifically bound [3H]L-glutamate. When applied by bath perfusion to the cell body membrane of the cockroach fast coxal depressor motor neurone, acromelic acid generated slow, prolonged, dose-dependent depolarizations at concentrations of 0.3 microM and above. Thus acromelic acid is among the most potent of the excitatory amino acids tested to date on insect neurones.

Animals↗

Aberrations of the APC gene in primary breast carcinoma.

Aberrations of the APC gene, which plays an important role in the genesis of familial adenomatous polyposis and colorectal carcinoma, were investigated in 31 surgical specimens of primary breast carcinoma. These studies utilized the polymerase chain reaction followed by restriction-fragment-length polymorphism and single-strand-conformation polymorphism analyses combined with tumor cell enrichment by cell sorting. Loss of heterozygosity at the APC locus was detected in 8 (38%) of 21 informative cases, but only 2 (6%) of 31 tumors carried a mutated APC gene. Direct DNA sequencing analysis confirmed mutations at codon 1081 (AGC to ATC) resulting in an amino acid substitution of serine for isoleucine, and at codon 1096 (CAG to CAT) resulting in a substitution of glutamine for histidine. There were no significant correlations between the loss of heterozygosity or mutation at the APC locus and any clinicopathological characteristics. Our present observations suggest that the mutations of the APC gene may play an important role in the genesis of certain breast carcinomas, and that another tumor-suppressor gene, which is the true target of frequent loss of heterozygosity, may exist near the APC gene.

Base Sequence↗

A marked increase in intracellular Ca2+ concentration induced by acromelic acid in cultured rat spinal neurons.

Acromelic acid, a kainate derivative of natural origin, markedly increased intracellular Ca2+ concentration ([Ca2+]i) in cultured rat spinal neurons in a concentration dependent manner; the half effective concentration (EC50) was 1.3 microM. Acromelic acid was more potent in increasing [Ca2+]i than any other glutamate receptor agonists tested, and the rank order of the activity was as follows: acromelic acid > alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) > kainate > N-methyl-D-aspartate (NMDA) > L-glutamate. Acromelic acid did not increase the [Ca2+]i in a Ca(2+-)free medium. 2,3-Dihydroxy-9-nitro-7-sulfamoylbenzo(F)quinoxaline (NBQX) completely inhibited the [Ca2+]i increase induced by acromelic acid. These results suggest that the [Ca2+]i increase was not through Ca2+ mobilization from intracellular stores but due to Ca2+ influx mediated by the activation of non-NMDA receptors. Acromelic acid increased the [Ca2+]i in rat hippocampal neurons as well; however, the EC50 (6 microM) was considerably higher than that in spinal neurons. The marked increase of [Ca2+]i in cultured spinal neurons would explain, at least in part, the earlier findings that systemic administration of acromelic acid causes selective degeneration confined to lower spinal interneurons.

Animals↗

Mechanisms of the development of trazodone withdrawal symptoms.

Three cases developed withdrawal symptoms of trazodone despite gradual discontinuation of therapeutic doses of the drug. This report suggests that effects of trazodone and its metabolite m-chlorophenylpiperazine on the serotonergic system, which may result in noradrenergic rebound after discontinuation, and short half-lives of these compounds are involved in the development of these symptoms. From a clinical point of view, we suggest that trazodone should be tapered off at a very slow rate.

Adult↗

Correlation between prolactin response and therapeutic effects of zotepine in schizophrenic patients.

The correlation between prolactin response and therapeutic effects of zotepine, as assessed by the Brief Psychiatric Rating Scale, was studied in 24 schizophrenic patients (12 males, 12 females), after 4 weeks of treatment. The daily dose was 100 mg in the first week, and 200 mg for the next 3 weeks. There were significant (p < 0.05) positive correlations between changes in serum prolactin concentration and amelioration scores of positive or total symptoms in males only. Thus, prolactin response may reflect therapeutic effects of zotepine, at least in males.

Adolescent↗

Adverse effects of zotepine and their relationship to serum concentrations of the drug and prolactin.

Adverse effects of zotepine, an antipsychotic drug, and their relationship to serum concentrations of the drug and prolactin were investigated in 28 schizophrenic in-patients. The daily dose was 100 mg during the first week and 200 mg during the next 3 weeks. Adverse effects were evaluated by the UKU Side Effect Rating Scale (21 items). The mean (+/- SD) total UKU score at the end of the study was 3.1 +/- 2.5, indicating mild adverse effects. The scores of psychic adverse effects at 2 weeks and total adverse effects at 3 and 4 weeks were significantly higher in nonresponders than in responders (p < 0.05). Furthermore, there was a significant inverse correlation between percent improvement in total Brief Psychiatric Rating Scale (BPRS) scores and total UKU scores at 4 weeks (p < 0.05). These results suggest a relationship between poor clinical response and increased adverse effects during zotepine treatment. Only the scores of akathisia at 2 weeks showed a significantly positive correlation with serum zotepine concentrations (p < 0.05). No correlation was found between prolactin response and neurological adverse effects.

Adolescent↗

A CMOS integrated circuit for multichannel multiple-subject biotelemetry using bidirectional optical transmissions.

A CMOS integrated circuit for a noninvasive biological-signal telemetry system specified for use in medical and physiological studies of the influence of weightlessness in space is presented. The system can monitor multichannel (4 channels maximum) biological signals from multiple subjects (4 subjects maximum) in real time by using time multiplexing. A key technique, so-called synchronized multiple-subject telemetry, to achieve multiple-subject telemetry has been proposed. This technique utilizes bidirectional optical transmissions with direct and scattered infrared lights between an observer and each of the subjects. An experimental CMOS IC to give a small light-weight low-power, and smart telemetry instrument for use on animals has been developed. This IC is for evaluating circuit blocks of the implantable monolithic telemetry instrument. The major circuit blocks include CMOS digital circuits for synchronization, subject selection and time multiplexing, analog circuits for pulse interval modulation (PIM), and other blocks such as a CMOS optical pulse receiver and an LED driver. A preliminary experimental multichannel telemetry from two subjects has been performed with the implemented IC chips, and the principal operation of the multiple-subject optical biotelemetry has been demonstrated.

Aerospace Medicine↗

Improved detection of loss of heterozygosity at retinoblastoma gene locus in human breast carcinoma.

Loss of heterozygosity (LOH) at the retinoblastoma (Rb) gene locus was investigated in 33 breast carcinomas by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis after tumor cell enrichment by cell sorting. The efficacy of cell sorting was evaluated by comparing the results of PCR-SSCP with and without cell sorting. Ten of 17 (59%) informative cases showed LOH at this locus by cell sorting combined with PCR-SSCP, although LOH was detectable in six (35%) cases without cell sorting. Flow cytometry and histologic examination revealed that this underestimation may occur when the tumor cell population is less than 50% in the specimens analyzed. It is concluded that LOH of the Rb gene occurs more frequently in human breast carcinoma than previously thought, and thus may contribute significantly to the development and/or progression of this tumor.

Adenocarcinoma↗

A novel antagonist, phenylbenzene omega-phosphono-alpha-amino acid, for strychnine-sensitive glycine receptors in the rat spinal cord.

1. 3-[2'-Phosphonomethyl[1,1'-biphenyl]-3-yl]alanine (PMBA) is a novel glycine antagonist at strychnine-sensitive receptors. The chemical structure of PMBA, possessing both a glycine moiety and a phosphono group, is quite different from that of strychnine. 2. In the spinal motoneurone of newborn rats, glycine (100 microM-1 mM) induced depolarizing responses in a concentration-dependent manner. PMBA effectively inhibited depolarizing responses to glycine and other agonists, such as taurine and beta-alanine. The dose-response curves for glycine were shifted to the right in an almost parallel manner (pA2 value: 5.30 +/- 0.23, n = 5) by PMBA which was about 60 times less potent than strychnine (pA2 value: 7.08 +/- 0.21, n = 5) as a glycine antagonist. 3. PMBA (1-100 microM) did not interact with modulatory glycine sites on N-methyl-D-aspartate (NMDA) receptors, which suggests a high selectivity of PMBA for strychnine-sensitive glycine receptors. At considerably high concentrations (0.1 mM-1 mM), PMBA depressed responses to GABA (pA2 value: 3.57 +/- 0.24, n = 3). 4. PMBA inhibited the binding of [3H]-strychnine to synaptosomes from adult rat spinal cords; the IC50 values of PMBA, glycine and strychnine were 8 +/- 2, 9 +/- 3 and 0.08 +/- 0.04 microM, respectively (n = 5) for [3H]-strychnine (4.8 nM). 5. PMBA is a central excitant drug with relatively high potency and selectivity and should be useful as a pharmacological probe for analysing the mechanisms underlying physiological functions of glycine receptors.

Animals↗

Structural modification of cell wall mannans of Candida albicans serotype A strains grown in yeast extract-Sabouraud liquid medium under acidic conditions.

The cell wall mannans of two Candida albicans serotype A strains, NIH A-207 and J-1012 (abbreviated as A and J strains, respectively), cultured in yeast extract-Sabouraud liquid medium at pH 2.0, contained neither a phosphate group nor a beta-1,2-linked mannopyranose unit (H. Kobayashi, P. Giummelly, S. Takahashi, M. Ishida, J. Sato, M. Takaku, Y. Nishidate, N. Shibata, Y. Okawa, and S. Suzuki, Biochem. Biophys. Res. Commun. 175:1003-1009, 1991). In this study, the mannans obtained from A and J strains grown in pH 2.0 medium (abbreviated as mannans A2 and J2, respectively) exhibited quite different reactivities against rabbit anti-C. albicans and anti-Saccharomyces cerevisiae sera compared with those of mannans from the corresponding strains cultured in conventional medium at pH 5.9 (abbreviated as mannans A and J, respectively). Namely, mannans A2 and J2 lost reactivity against the former serum but reacted with the latter serum to a higher extent than mannans A and J. In order to account for these difference in more detail, mannans A2 and J2 were subjected to acetolysis. Elution profiles of the acetolysates were completely different from those of acetolysates obtained from mannans A and J reported in our previous papers. The 1H nuclear magnetic resonance spectra of the oligosaccharides from mannans A2 and J2 obtained by this procedure indicate that the side chains are composed of alpha-linked mannopyranose units densely linked to the alpha-1,6-linked backbone. The long side chains containing one alpha-1,3-linked mannopyranose unit are markedly increased.

Candida albicans↗

Overexpression of genes of an extreme thermophile Thermus thermophilus, in Escherichia coli cells.

The 3-isopropylmalate dehydrogenase gene from an extreme thermophile, Thermus thermophilus, was not expressed in Escherichia coli unless a palindromic structure around the ribosome binding site was eliminated or a leader open reading frame was introduced into the upstream flanking region of the gene. This report suggests a way to increase the expression of this gene, with a high G+C content, in E. coli.

3-Isopropylmalate Dehydrogenase↗

Lack of effect of ouabain on calcium homeostasis in rat platelets: comparative study with human platelets.

The precise mechanisms of Ca2+ handling in rat platelets are not fully understood. We sought to determine whether rat platelets possess a Na(+)-Ca2+ exchanger. First, we investigated the time course of the effect of ouabain (10(-4) M) on cytosolic sodium concentration ([Na+]i) and Ca2+ homeostasis in platelets from Wistar rats in comparison with those from humans. Ouabain increased platelet [Na+]i in both rat and human platelets. Whereas ouabain induced a time-dependent increase in basal and thrombin-stimulated (0.3 units/ml) cytosolic calcium concentration ([Ca2+]i) in human platelets, no change was found in rat platelets. Furthermore, 90-min pretreatment of rat platelets with ouabain did not affect the [Ca2+]i response to thrombin (0.1-1.0 units/ml) or a maximal dose of ionomycin (5 microM). Also the decline in [Ca2+]i after the peak response evoked by these agonists in the absence of extracellular Ca2+ was not changed by ouabain pretreatment. Similarly, replacement of extracellular Na+ had no influence on any of these determinations. Thus decreasing the plasma membrane Na+ gradient did not affect basal [Ca2+]i, thrombin-induced mobilization of Ca2+ from intracellular stores, internal Ca2+ discharge capacity, or Ca2+ extrusion from cytosol of rat platelets. In contrast to human platelets, a Na(+)-Ca2+ exchange mechanism does not appear to play a significant role in Ca2+ homeostasis of rat platelets.

Animals↗

Lack of increase in platelet Ca2+ and Na+ in deoxycorticosterone acetate-salt hypertensive rats.

We have previously characterized abnormal Ca2+ handling in platelets of spontaneously hypertensive rats (SHRs). In this study, we investigated whether cellular Ca2+ metabolism and/or Na+ concentration is altered in platelets of deoxycorticosterone acetate-salt hypertensive rats (DOCA rats). The resting cytosolic Ca2+ concentration ([Ca2+]i) in platelets was significantly lower in DOCA rats than controls (54.5 +/- 1.4 vs. 61.2 +/- 2.3 nmol/l). The amplitude of the [Ca2+]i transient induced by thrombin was significantly increased in the absence, but not the presence, of external Ca2+ in DOCA rats compared with control rats. The [Ca2+]i response to 5 mumol/l ionomycin in the Ca(2+)-free buffer was greater in DOCA rats than in controls (546 +/- 23 vs. 470 +/- 18 nmol/l), indicating larger intracellular Ca2+ stores. The rate of recovery of [Ca2+]i after the peak response to thrombin was decreased in DOCA rats (79% at 0.1 U/ml and 91% at 1.0 U/ml thrombin of control rats). Cytosolic Na+ concentration ([Na+]i) in platelets was similar in DOCA and control rats. Altered Ca2+ levels are not correlated with [Na+]i in this salt-sensitive hypertensive model. Therefore, an increased [Ca2+]i is not an obligatory phenomenon in hypertension.

Animals↗

Factors improving L-threonine production by a three L-threonine biosynthetic genes-amplified recombinant strain of Brevibacterium lactofermentum.

When a Brevibacterium lactofermentum L-threonine producer that accumulated L-lysine as well, was transformed with a recombinant plasmid carrying the indigenous hom, thrB, and thrC genes, delayed growth and plasmid instability were observed. Addition of organic nutrients, vitamins (thiamine.HCl and d-biotin), and NaCl under the optimal culture conditions solved these problems and further increased threonine production in a small jar fermentor.

Brevibacterium↗

Erythrocyte Na+/K(+)-ATPase and membrane and serum lipid profiles: as related to alcohol, body mass index and blood pressure.

Erythrocyte Na+/K(+)-pump activities have been measured in hypertensives, alcohol consumers and obese persons, but the results have been variously reported as decreased, increased or unchanged. We analyzed the relationships between erythrocyte Na+/K(+)-ATPase activities and the membrane and serum lipid profiles in 83 middle-aged men, to clarify the reasons for these inconsistencies. Increases in erythrocyte Na+/K(+)-ATPase activity related closely to decreases in cholesterol to phospholipid (C/P) ratio of the erythrocyte membrane. Decreases in the C/P ratio in turn related closely to elevations of serum triglycerides (TG) with increasing body mass index, and weakly to the volume of alcohol consumed. Thus, erythrocyte Na+/K(+)-ATPase activities depend largely on the membrane and serum lipid profiles as related to body weight and alcohol consumption, and which may be a cause of the previous conflicting findings. Erythrocyte Na+/K(+)-ATPase showed a positive association with blood pressure, independently of age, body mass index and serum gamma-glutamyl transpeptidase levels. Although the biological link of elevated erythrocyte Na+/K(+)-ATPase with the rise in blood pressure remains unclear, it may be a reflection of hyperinsulinemia in the subjects with a higher blood pressure due to overweight or excessive alcohol consumption.

Adult↗

Antigen (DNP-As)-induced allergic rhinitis model in guinea pigs.

In guinea pigs, an IgE antibody was produced by intraperitoneal injection of antigen (DNP-As) containing Al(OH)3 and booster inhalation of the antigen into the nasal cavity. Experimental allergic rhinitis was induced by the perfusion of antigen solution into the nasal cavities of actively sensitized guinea pigs. Severity of allergic rhinitis was assessed by determining release of histamine and leakage of dye into the nasal cavity. The antigen-induced release of histamine was significantly increased at 0 to 15 minutes following antigen administration but then decreased with time. The antigen-induced leakage of dye was sustained for 60 minutes after administration of the antigen. These results suggest that the DNP-As-induced allergic rhinitis model in guinea pigs is instrumental in evaluating the effect of various factors on allergic rhinitis.

Animals↗