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Biomedical subjects

M Tamaru

Publications and source records attributed to M Tamaru.

At least 37 records · Page 2Linked to original sources
PubMed1992

Excitatory amino acid receptors in brains of rats with methylazoxymethanol-induced microencephaly.

We used methylazoxymethanol-acetate (MAM), a potent alkylating agent, to produce microencephaly in offspring by injecting it into pregnant rats on day 15 of gestation. Binding activities of central excitatory amino acid receptors were examined in Triton-treated membranes prepared from brains of adult offspring with MAM-induced microencephaly (MAM rats). MAM rats exhibited approximately 40-50% reductions of the wet weights of the cerebral cortex, hippocampus and striatum compared to those in controls. In the cortex and hippocampus of MAM-rats, total bindings of [3H]glutamate (Glu) (which is sensitive to N-methyl-D-aspartate (NMDA) receptor), and strychnine-insensitive [3H]glycine (Gly) and (+)-5-[3H]methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (MK-801; a noncompetitive antagonist of NMDA receptor), were reduced to approximately 40% of those in controls. Similarly, in both regions of MAM rats, total bindings of [3H]kainate and DL-alpha-amino-3-[3H]hydroxy-5-methylisoxazole-4-propionic acid (an agonist of quisqualate receptors), were reduced to approximately 35-50% of those in controls. However, total bindings of these radioligands in the striatum of MAM rats were more than 65% of those in controls, despite the significant loss of striatum mass. However, specific bindings of radioligands in the striatum of MAM rats were elevated by more than 60% of those in controls, and Scatchard analysis revealed that elevations of [3H]Glu, [3H]Gly and [3H]MK-801 bindings were due to a significant increase in the densities of binding sites, with their affinities remaining unaltered. Spatial recognition ability examined by an 8-armed radial maze task was markedly impaired compared to those in controls. These results suggest that the proliferation of neurons bearing excitatory amino acid receptors (EAA) in the striatum is less affected by MAM treatment on day 15 of gestation than that in the cortex and hippocampus in spite of drastic weight loss in these brain regions. The significant reduction of EAA receptors in the cortex and hippocampus may be involved in the impairment of spatial memory observed in MAM-treated rats.

Animals↗
PubMed1992

Effects of cycloheximide and actinomycin D on radiation-induced apoptotic cell death in the developing mouse cerebellum.

Effects of cycloheximide and actinomycin D on radiation-induced cell death in the external granular layer (EGL) of the cerebellum were studied in vivo. Newborn mice were exposed to 0.24 Gy gamma-radiation, and dying cells which exhibited pyknosis of nuclei in the EGL were examined at various post-irradiation periods. The number of pyknotic cells began to increase 3 h after irradiation, reached a peak incidence at 6 h, and then gradually fell to the sham-irradiated level by 18 h. When pups were injected with cycloheximide 1 h after irradiation, cell death was suppressed for 6 h, but a peak mortality as high as in the case of radiation alone was attained at 15 h after irradiation. When pups were treated with cycloheximide twice, at 1 and 6 h after irradiation, cell death did not occur for 15 h, but then the incidence rose to a level similar to that after irradiation alone. These findings showed that radiation-induced cell death in the EGL is suppressed by cycloheximide until the chemical is metabolized. Hence, death is by apoptosis which is known to require macromolecular synthesis, and the 'signal' for apoptosis in the cell persists for at least 15 h after irradiation. On the other hand, actinomycin D injected immediately before or after irradiation did not affect the initiation of cell death; actinomycin D alone induced cell death.

Animals↗
PubMed1991

Age-related decreases of the N-methyl-D-aspartate receptor complex in the rat cerebral cortex and hippocampus.

Binding activities of central excitatory amino acid receptors were examined in Triton-treated membrane preparations of the cerebral cortex and hippocampus from brains of rats at 2, 7 and 29 months after birth. Aged rats exhibited a significant reduction of [3H]glutamate (Glu) binding displaceable by N-methyl-D-aspartate (NMDA), as well as strychnine-insensitive [3H]glycine binding in both central structures, as compared with those in young rats. Binding of [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne maleate (MK-801), a non-competitive NMDA antagonist used to label the activated state of ion channels linked to NMDA-sensitive receptors, also decreased with aging irrespective of the experimental conditions employed. Scatchard analysis revealed that reduction of both [3H]Glu binding and [3H]MK-801 binding were due to a significant decrease in the densities of binding sites with aging, with their affinities being unaltered. Binding of [3H]D,L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), which is a specific agonist for quisqualate-sensitive receptors, was unchanged with aging when determined in the absence of 100 mM potassium thiocyanate (KSCN). However, AMPA binding determined in the presence of added KSCN was about 25% reduced in both brain regions of aged rats. Binding of [3H]kainate to kainate-sensitive receptors was unchanged with aging. These results suggest that glutaminergic neurotransmission mediated by NMDA-sensitive receptors may be selectively impaired with aging in the hippocampus and cerebral cortex among 3 different subclasses of excitatory amino acid receptors in the brain.

Aging↗
PubMed1991

Effects of fetal treatment with methylazoxymethanol acetate on radial maze performance in rats.

Pregnant rats (Wistar-Imamichi strain) were treated with 15 mg/kg/d of methylazoxymethanol acetate (MAM) on days 13-15 of gestation. Nine male rats, which were randomly selected from the MAM-treated offspring (MAM rats), were examined for their spatial recognition ability by the radial maze technique and compared with control offspring. Although the performances of MAM rats were inferior to the control, they could reach the predetermined criterion within 15 trials. Subsequent retention tests revealed the drastic impairment of performance in MAM rats when the retention interval was over 15 min. The total activity of choline acetyltransferase showed a significant decrease in the hippocampus and cerebral cortex of MAM rats. These results suggest that working memory disorders of MAM rats on radial maze tasks may be due to the lowering of cholinergic functions in their hippocampus and cerebral cortex.

Animals↗
PubMed1991

Antithyroid drug therapy for Graves' hyperthyroidism: is long-term administration of a small maintenance dose necessary?

This retrospective study serves as an inquiry into the common practice of long-term administration of small maintenance doses of either methyl-mercaptoimidazole (MMI) or propylthiouracil (PTU) to Graves' hyperthyroid patients who became euthyroid with primary large doses of the same drugs. One hundred and two patients with Graves' hyperthyroidism treated with antithyroid drug (ATD) were studied. Sixty-one were treated with conventional long term therapy and 41 were treated with short-term therapy. Small maintenance doses of ATDs were not administered to the short-term therapy patients. The duration of long-term therapy was 28.6 +/- 20.2 months (from 12 to 48 months) and that of short-term therapy was 8.4 +/- 1.8 months (from 5 to 11). Post therapy and follow-up observation continued for 19.0 +/- 2.7 months (16-25 months) in both long-term and short-term patients. Of the 61 long-term therapy patients, 20 were relapsed and 41 (67.2%) continue to remain in remission. So too, of the 41 short-term therapy patients, 14 relapsed and 27 (65.9%) still remain in remission. There was no statistical difference between the long-term and short-term therapy group in age, sex, duration of symptoms before diagnosis, antithyroid antibodies, radioactive iodine uptake, free thyroid hormone levels or goiter size before treatment or in TBII levels at cessation of ATD. It is concluded that 'short-term ATD therapy' without a maintenance dose is sufficient and saves several months of the patient's and clinician's time.

Adult↗
PubMed1991

Serum free triiodothyronine to free thyroxine ratio enables early prediction of the outcome of antithyroid drug therapy in patients with Graves' hyperthyroidism.

This study scrutinizes the correlation between serum free triiodothyronine (FT3) to free thyroxine (FT4) ratios and the eventual outcome of antithyroid drug (ATD) therapy in patients with Graves' disease. Forty-four patients with Graves' thyrotoxicosis were treated with methylmercaptoimidazole (methimazole). During the follow-up, 16 patients relapsed in the short period of one to five months after cessation of the drug (relapse group), and 28 patients remained in remission when checked at 12 to 20 months after treatment (remission group). Serum FT3 to FT4 ratios [(pg/ml/ng/dl) x 10] were less than 55 throughout ATD therapy in 27 of the 28 remission patients whereas the ratios of the relapse group exceeded 55 from the early phase of methimazole treatment in 10 of 16 patients. In eight of these 10 patients the increased ratios were detected within three months of therapy (1 month, 3 patients; 2 months, 4 patients; 3 months, 1 patient). The ratios for the remaining two patients rose above 55 at the fifth and sixth months. There was no statistical difference between the remission and relapse groups in the FT3 to FT4 ratios either before nor at the completion of the treatment. However, a clear difference could be measured at a point during the therapy. Those in whom this difference was pronounced later underwent relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Pentavalent technetium-99m-DMSA uptake in a patient having multiple myeloma without amyloidosis.

A pentavalent 99mTc-dimercaptosuccinic acid (DMSA) scan was performed on a patient with multiple myeloma without amyloidosis. A high accumulation of the tracer was found in numerous tumors. We believe that the accumulation of DMSA is unrelated to amyloidosis and that the DMSA scan may have potential for the staging of tumors in patients presenting with multiple myeloma.

Bone Neoplasms↗
PubMed1990

Selective activation of testis-specific genes in cultured rat spermatogenic cells.

During mammalian spermatogenesis the isozyme pattern of a glycolytic enzyme, phosphoglycerate kinase (PGK; ATP: 3-phospho-D-glycerate 1-phosphotransferase, EC 2.7.2.3), changes from the somatic-type PGK-1 to the testis-specific PGK-2, and this change has been suggested to involve transcription switch. We have isolated genomic DNA fragments which code for the mouse PGK isozymes and determined the transcription start site of each gene. The results demonstrate that transcriptions of the two PGK genes are initiated at multiple sites under the control of TATA box-lacking promoters. The putative promoter regions of the two genes contain several distinct sequences known as the CCAAT box and the GC box which possibly bind CCAAT-binding proteins and Sp1, respectively. We next developed a culture system in which spermatogenic gene expression is partly reproduced. When spermatogenic cells of 20-day-old rats were cultured, transcripts from PGK-2 and another spermatogenic gene PRPS3 became detectable, while expression of other non-spermatogenic genes did not significantly change during culture. These results suggest that two spermatogenic genes PGK-2 and PRPS3 were activated in culture according to a developmental program of spermatogenesis. Thus, this culture system may be useful for studying the molecular mechanism underlying mammalian spermatogenic gene expression.

Animals↗
PubMed1990

Transcription switch of two phosphoglycerate kinase genes during spermatogenesis as determined with mouse testis sections in situ.

In order to elucidate the mechanistic interpretations underlying differential expression of the two phosphoglycerate kinase (PGK) genes during mammalian spermatogenesis, localization of its mRNAs in mouse testis sections was determined by in situ hybridization. MRNA for nonsperm-type PGK-1 was identified in nongerminal Leydig and Sertoli cells, spermatogonia, and spermatocytes, but was not detected in spermatids. In contrast, mRNA for sperm-type PGK-2 was notable in leptotene spermatocytes, becoming most abundant in pachytene spermatocytes. It was amply present in spermatids only up to step 10, completely disappearing after step 12. It is possible to assume that a transcription switch of the two PGK genes ensued following the onset of meiosis. These findings taken together with previous observations indicate that differential expression of the two PGK genes during mammalian spermatogenesis is regulated at the transcriptional and post-transcriptional levels.

Animals↗
PubMed1990

The classification of the low birth-weight infants from the viewpoint of mental development.

Periodical checkups on 206 infants were carried out in order to elucidate which of various factors would pose decisive influence upon the retardation of mental development after birth with the AIKEN method. Correlations between average DQ (development quotient) and figures of physical measurements at birth were sought after. Consequently, weeks of gestation, body weight, cephalic circumference and body length at birth revealed certain correlation with the retardation of mental development. Multiple regression analysis disclosed highly significant correlations of body length and cephalic circumference toward the birth weight. Therefore, both weeks of gestation and birth weight are the direct contributory factors to average development quotient. Based on this result, a prediction equation for the mental development after birth has been proposed. Low average DQ was found in high percentages among infants born with toxemia of pregnancy or premature rupture of membranes. However, it is suggested that they are not the direct causes of such retardation, but are rather provoking short weeks of gestation and low birth weight. In summary, the newborn with less than 37 weeks of gestation and below 2,000 grams of birth weight would be named and classified as a SFD (small for dates) with the problem for mental development (MD-SFD).

Birth Weight↗
PubMed1989

Effects of hemicholinium-3 and sodium ions on choline uptake system in excised superior cervical sympathetic ganglia of rats.

Active choline uptake by rat superior cervical sympathetic ganglia (SCG), which contain abundant cholinergic nerve terminals, was studied with respect to sensitivity to inhibition by hemicholinium-3 (HC-3) and dependence on extracellular Na under standard conditions of assay. Choline was taken up by a single saturable process with apparent Km = 3.07 x 10(-5) M and Vmax = 286 pmoles/min/mg protein. Neither denervation followed by degeneration of cholinergic nerve terminals nor axotomy with successive neuronal degeneration significantly decreased in choline uptake by the ganglia in vitro. HC-3 dose-dependently inhibited ganglionic choline uptake more effectively at lower than at higher choline concentrations. HC-3 sensitive inhibition of ganglionic choline uptake was not seen in young rats one week after birth but appeared with maturity, attaining approximately 50% maximal inhibition in adult SCG. Extent of inhibition by HC-3 and Na dependence of ganglionic choline uptake was not altered by denervation or axotomy.

Aging↗
PubMed1989

Decrease of atrial natriuretic peptide content in rat superior cervical sympathetic ganglion after denervation and axotomy.

We found atrial natriuretic peptide (ANP), known as a humoral factor in regulating body fluid volume and blood pressure, in considerable quantities in rat superior cervical sympathetic ganglion (SCG) by radioimmunoassay after separation with reverse-phase HPLC. Although the ANP content of the immature rat 1 week after birth was low, it doubled at 2 weeks and then increased gradually, until it reached the adult level. Denervation caused a rapid decrease in the ANP content to half of the intact SCG level after 3 h, which then fell to 10% of the control value on day 2 after operation. The time course of ANP content reduction after denervation was similar but rather faster than that of activity of the acetylcholine-synthesizing enzyme, choline acetyltransferase, an observation suggesting that ANP may partly contribute to cholinergic synaptic transmission. On the other hand, axotomy produced a rather slower decrease in the ANP content than did denervation. Enucleation and sialoadenectomy also caused a considerable reduction of the ANP content. Thus, part of the ANP found in the ganglion is apparently transported from sympathetically innervated extraganglionic organs via retrograde axoplasmic flow.

Aging↗
PubMed1989

Analysis of the expression of two phosphoglycerate kinase genes in a mouse cultured cell line during activation and inactivation of the c-myc gene.

The effect of a change in the concentration of c-myc protein on the expression of genes for two phosphoglycerate kinase isozymes was investigated. The steady state levels of messenger ribonucleic acids (mRNAs) for sperm-type and non-sperm-type proteins were determined by blot hybridization using the RNA of the mouse cell line 38-2 containing the inducible rat c-myc gene cultured under various conditions. Without induction the c-myc gene. mRNA for non-sperm-type protein was detected at a level that remained essentially constant during both activation and inactivation of the c-myc gene. mRNA for sperm-type protein was not detected in 38-2 cells cultured under any conditions used. Change in the amount of c-myc protein alone does not appear to bring about a switch of the expression of the two phosphoglycerate kinase genes during spermatogenesis in mouse testis.

Cell Line↗
PubMed1988

Structure-activity studies on inhibition of choline uptake by a mouse brain synaptosomal preparation: basic data.

Over 80 substances were studied for their inhibition of high-affinity uptake of [3H]choline into a mouse brain synaptosomal fraction. Kinetic experiments tested a number of them for competitive behavior. A minimal provisional model for the choline uptake process is envisioned that is consistent with current data and with relevant observations in the literature. There are two hydrophilic anionic sites on the choline transporter that are separated from each other by a cationic hydrophobic domain. Association of choline in a Na+-dependent manner with one or both of the sites is necessary for the transport of choline to take place. The choline binding anionic sites are sufficiently large and/or flexible to allow attachment of cationic moieties larger than choline. The cationic hydrophobic domain of the transporter is flexible, probably tending to planarity. The length of the hydrophobic region between the anionic sites is approximately that of 10 extended methylene groups, and the minimal width is approximated by the distance across the condensed ring system of chlorpromazine. The probability of attachment of the highly hydrophilic choline to its binding sites is increased both by hydrogen-bonding to a proton-acceptor within the anionic sites and by repulsion from the cationic hydrophobic region. A number of substances that potently and competitively inhibit high affinity choline uptake possess quaternary ammonium groups and neutral or negatively charged lipophilic groups. In general, substances in which two quaternary ammonium groups are separated by an appropriately configured hydrophobic group and which can combine with both anionic sites and the hydrophobic region between them are more potent inhibitors than monoquaternary substance with the same or similar groups. However, substances with a single high-affinity quaternary group and an appropriately structured hydrophobic group, e.g. the trimethoxy-3-butynyl quaternary ammonium compounds, possess inhibitory efficacies similar to those shown by the most potent bisquaternaries. The above suggests that further delineation of the characteristics of the structures of the above sites of the transporter could lead to devisal of more potent reversible inhibitors of choline uptake than now are available.

Animals↗
PubMed1988

Brain changes in rats induced by prenatal injection of methylazoxymethanol.

Various doses (0, 1, 5, 10, 15, 20, or 25 mg/kg) of methylazoxymethanol acetate (MAM), a potent alkylating agent, were injected singly into pregnant rats intraperitoneally on day 15 of gestation. Relationships between brain weights and neurochemical changes in the cerebral hemispheres (CHs; cerebral cortex and subjacent white matter, hippocampus, amygdala) and remainder of the brain (BGDM; basal ganglia, diencephalon, and mesencephalon) were examined at 60 days of age in offspring; varying degrees of microencephaly were observed. Dose-dependent reductions in the weights of CH and BGDM were observed. Reductions in total DNA content positively correlated with decreases in brain weights also observed. Dose-dependent elevations of noradrenaline (NA) and dopamine (DA) were observed in CH at MAM levels 10 mg/kg and above; dose-dependent elevations of 5-hydroxytryptamine (5-HT) were observed at 15 mg/kg and above; and in BGDM at 20 mg/kg and above dose-dependent elevations for NA and 5-HT were observed; dose-dependent elevations at 15 mg/kg and above were observed for DA. Monoamine concentrations were negatively correlated with brain weights or total DNA contents. NA and DA concentrations increased to the extent of approximately 1.3 times of control at a time when an 18% loss of CH weight was noted in animals treated with 10 mg/kg MAM. It is suggested that the above variables might be appropriately sensitive neurochemical markers for detecting minor developmental anomalies in the brain.

Alkylating Agents↗
PubMed1988

Neurochemical effects of prenatal treatment with ochratoxin A on fetal and adult mouse brain.

Ochratoxin A (OA) is a mycotoxin produced by several storage fungi, such as Aspergillus ochraceus and several Penicillium species. OA (3 mg/kg) was given intraperitoneally to pregnant mice on day 11 of gestation (day 1 = day of insemination), and neurochemical changes in brains of their offspring were examined at fetal and adult stages. OA treatment produced retardation of intrauterine growth as well as microencephaly and reductions in total weight and DNA content of fetal brains. Specific activities of lysosomal enzymes in fetal brains began to increase by the 2nd day after treatment and to reach peak activities by the 3rd or 4th day after injection, indicative of cell death in the developing brains. Examination of brain regions of offspring three months after birth revealed that both tissue weight and DNA content were reduced to 80% of control in cerebral hemispheres (CHs; cerebral cortex and subjacent white matter, hippocampus, and amygdala) and to 90% of control in remainder of the brain (BGDM; basal ganglia, diencephalon, and mesencephalon). Total content of noradrenaline (NA), dopamine (DA) 5-hydroxytryptamine (5-HT) in treated CH showed about 15% reduction, although, expressed on a tissue weight basis, concentrations of these monoamines were increased by about 15%. Total DA content in BGDM was also reduced to 85% of controls, but total content of NA and 5-HT in BGDM and pons-medulla oblongata did not change. These results suggest that synaptogenesis of monoamine neurons in the cerebrum is impaired by prenatal treatment with OA, and that dopaminergic neurons show a slight selective vulnerability to the toxin.

Animals↗