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Biomedical subjects

S Miwa

Publications and source records attributed to S Miwa.

At least 253 records · Page 14Linked to original sources
PubMed1987

Chromatographic analysis of human erythrocyte pyrimidine 5'-nucleotidase from five patients with pyrimidine 5'-nucleotidase deficiency.

Human erythrocyte pyrimidine 5'-nucleotidase (P5N) was separated into two subclasses. P5N-I and P5N-II, by DEAE Bio-Gel A column chromatography. Their enzymological properties were studied using five normal subjects and five patients with different P5N deficiencies. Study of the normal subjects showed that P5N-I and P5N-II have distinctive properties, and P5N-II is similar to the 5'-nucleotidase in rat liver cytosol. The P5N-II from the five subjects with this deficiency had normal activity and other normal enzymological properties. However, the P5N-I from these patients had abnormal properties, including reduced activity. These variant enzymes had a high Michaelis constant for substrate cytidine 5'-monophosphate and were heat stable. The optimum pH was shifted towards the acidic side in two patients, towards the basic side in one, and was unchanged in the other two. These results strongly suggest that the main cause of P5N deficiency is an abnormality of P5N-I, probably arising from a structural gene mutation.

5'-Nucleotidase↗
PubMed1987

Determination of serotonin turnover in the rat brain using 6-fluorotryptophan.

After intraperitoneal injection of rats with 6-fluorotryptophan (6-FT), brain 5-hydroxytryptamine (5-HT) levels decreased exponentially over 1 h. Depletion was dose-dependent and maximum depletion was observed at 200 mg/kg. 6-FT (200 mg/kg) did not significantly alter the content of 5-hydroxyindoleacetic acid. Turnover rates of 5-HT obtained by the 6-FT and other methods were fairly consistent. 6-FT had little effect on the content of noradrenaline and dopamine. These data suggest that 6-FT completely inhibits tryptophan hydroxylase, in vivo, without affecting the release of 5-HT from 5-HT neurons and with little effect on the activities of tyrosine hydroxylase. Therefore, 6-FT is a good pharmacological tool for studying the turnover rate of 5-HT in the brain.

Animals↗
PubMed1987

[Anemias].

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Anemia↗
PubMed1987

Differential effects of hypoxia on the turnover of norepinephrine and epinephrine in the heart, adrenal gland, submaxillary gland and stomach.

The authors examined the effects of hypoxia (8% O2 in N2) on the turnover rates of norepinephrine (NE) and epinephrine (E) in the heart, adrenal gland, submaxillary gland and stomach. The turnover rates were estimated by measuring the decrease in the content of NE and E after an i.p. injection of alpha-methyl-p-tyrosine (250 mg/kg), an inhibitor of tyrosine hydroxylase. After a 4-h exposure to hypoxia, the turnover rate of NE in the heart and those of NE and E in the adrenal gland were increased, whereas that of NE in the submaxillary gland was decreased. The turnover rate of NE in the stomach was unchanged. Pretreatment with hexamethonium, a ganglionic nicotinic receptor blocker, abolished the hypoxia-induced changes in the turnover rate of NE or E in the heart, adrenal gland and submaxillary gland. Furthermore, transection of the spinal cord at the level of C5-6 abolished hypoxia-induced alterations in the turnover rate of NE and E in the adrenal gland and submaxillary gland. In contrast, the hypoxia-induced changes seen in the heart persisted, although at a lower level, even after transection. These results show that the effects of hypoxia on the activities of the sympathoadrenal system differ depending on the organs; activities are increased in the heart and adrenal gland, decreased in the submaxillary gland and unchanged in the stomach. Furthermore, the present data suggest that hypoxia-induced alterations in the activities of cardiac sympathetic nerves originate in both the brain and spinal cord, including preganglionic neurons, whereas changes in the activities of the sympathetic nerves to the adrenal gland and submaxillary gland originate mainly in the brain.

Adrenal Glands↗
PubMed1986

Characterization of purine nucleoside phosphorylase in leukemia.

Purine nucleoside phosphorylase (PNP) activity was determined in mononuclear cells from 49 patients with various types of leukemia. A low level of PNP activity was found in mononuclear cells from patients with acute myeloid and lymphoblastic leukemia and with chronic lymphocytic leukemia. Enzymatic and immunological studies on PNP from leukemic cells of these patients revealed no differences in Michaelis constant for inosine, thermostability, electrophoretic mobility, immunological reactivity, or specific activity between the PNP of leukemic cells and that of normal mononuclear cells. These results suggest that the decrease in PNP activity of leukemic cells is due to a decreased rate of enzyme synthesis. Thus, the abnormality of PNP activity might be due to an alteration in the regulatory mechanism of enzyme synthesis in the purine metabolism in the leukemic clone.

Humans↗
PubMed1986

Sympathetic denervation and alpha adrenoceptors in dog cerebral arteries.

The magnitude of the noradrenaline-induced contractions of dog middle cerebral arteries was less than that seen in the vertebral, common carotid, femoral and renal arteries. Noradrenaline and clonidine produced a similar magnitude of maximum contractions in the middle cerebral arteries, whereas methoxamine produced no significant contractions in the same arteries. In the extracranial arteries, noradrenaline and methoxamine produced significantly larger contractions than clonidine. Binding studies revealed no specific 3H-prazosin binding sites in the cerebral arteries, though such binding sites were evident in the case of extracranial arteries. 3H-Yohimbine binding studies revealed the presence of two classes of binding sites with high and low affinities in both cerebral and extracranial arteries. After superior cervical ganglionectomy, noradrenaline- and clonidine-induced contractions of the denervated middle cerebral arteries were not altered, compared with the control arteries. A 3H-yohimbine binding study was also performed using the denervated cerebral arteries. This study revealed that there was a low affinity 3H-yohimbine binding site, whereas high affinity 3H-yohimbine binding site was not detectable. These results suggest the presence of two different binding sites with high and low affinity for alpha 2 adrenoceptors, which we are classifying into alpha 2H and alpha 2L subtypes. The high affinity sites, alpha 2H adrenoceptors, are presynaptically located while the low affinity sites, alpha 2L adrenoceptors, located postsynaptically. The noradrenaline-induced contractions are probably mediated by postsynaptic low affinity sites of alpha 2 adrenoceptors (alpha 2L adrenoceptors) in the cerebral arteries and mainly by alpha 1 adrenoceptors in the extracranial arteries.

Animals↗
PubMed1986

Effects of hypoxia on the activities of noradrenergic and dopaminergic neurons in the rat brain.

The effects of hypoxia (10% O2, 90% N2) on the content, biosynthesis, and turnover of noradrenaline (NA) and 3,4-dihydroxyphenylethylamine (dopamine, DA) in the rat brain were examined. Up to 24 h following exposure to hypoxia, NA content in the whole brain was decreased, whereas DA content remained unchanged. The accumulation of 3,4-dihydroxyphenylalanine (DOPA) after central decarboxylase inhibition was decreased. The turnover rate of DA after synthesis inhibition was markedly decreased up to 8 h and returned to the control level within 24 h. In contrast, the turnover rate of NA was all but unchanged, except for a 4-h exposure. The 2-h exposure to the hypoxic environment resulted in a significant decrease in NA content and DOPA accumulation in all brain regions tested, but no significant change was observed in DA content. The turnover rate of DA was remarkably decreased in all brain regions tested, whereas the rate of NA was slightly decreased only in the cerebral cortex and hippocampus. These results suggest that although hypoxia decreases the biosynthesis of both NA and DA, the effects of oxygen depletion on the functional activities of NA neurons differ considerably from those of DA neurons: Only in the cerebral cortex and hippocampus are the NA neurons slightly sensitive to hypoxia, whereas the DA neurons are most sensitive in all brain regions.

Animals↗
PubMed1986

The effects of cinepazide on the content, biosynthesis and turnover of noradrenaline, dopamine and 5-hydroxytryptamine in the rat brain under room air and hypoxia.

The effects of cinepazide, a vasodilator, on the content, biosynthesis and turnover of noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) in the rat brain were examined under room air and hypoxia (10% O2, 90% N2). Under room air, cinepazide had no significant effects on the content of NA, DA, 5-HT and 5-hydroxyindoleacetic acid (5-HIAA), the accumulation of 3,4-dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) after central decarboxylase inhibition, and the depletion of NA, DA and 5-HT after synthesis inhibition. After 2 hr-exposure to hypoxia, the content of NA, 5-HT and 5-HIAA was decreased, whereas the content of DA was unchanged. The accumulation of DOPA and 5-HTP was decreased. The depletion of DA and 5-HT was inhibited by hypoxia, whereas the depletion of NA was unaffected. Under hypoxic conditions, cinepazide had no effects on the content of NA, DA and 5-HT, the accumulation of DOPA and 5-HTP, and the depletion of NA and DA, whereas cinepazide increased both the rate of 5-HT depletion and the content of 5-HIAA. The present data suggest that cinepazide selectively stimulates the functional activities of 5-HT neurons in the brain, which are depressed by hypoxia.

5-Hydroxytryptophan↗
PubMed1986

Abnormal arrangements in the alpha- and gamma-globin gene clusters in a relatively large group of Japanese newborns.

Data were obtained on blood samples from a relatively large group (264) of healthy Japanese newborns, collected at hospitals in Tokyo, Kurashiki, and Ube. The studies included an evaluation of anomalies in alpha-globin gene and gamma-globin gene arrangements using gene mapping and gamma-chain composition analyses. The results confirmed the rarity of alpha-thalassemia among Japanese; only a few babies had alpha-thalassemia-2 trait (the -3.7-kilobase [kb] deletion), while others had alpha-globin gene triplications (both the alpha alpha alpha anti-3.7 and the alpha alpha alpha anti-4.2 types). Among the gamma-globin gene anomalies that were observed, a few babies had the -A gamma-A gamma- globin gene arrangement or the -G gamma A gamma- type of deletion. The gamma-chain triplication (-G gamma-A gamma G gamma-A gamma-) occurred in 10 out of 256 newborns, and its frequency exceeded that of its corresponding -G gamma A gamma- deletion by a factor of 5. The restriction endonuclease XmnI was a useful tool, in addition to the enzymes Bg1II and BclI, to evaluate and confirm the gamma-globin gene deletion and triplication. The A gamma T variant, which is the product of a mutant A gamma-globin gene, occurred at a frequency of 0.156. The chromosome carrying this mutant A gamma gene had a characteristic haplotype that was originally seen in black and Mediterranean patients with Hemoglobin (Hb) S or with beta-thalassemia.

Chromosome Mapping↗