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Biomedical subjects

M Shimada

Publications and source records attributed to M Shimada.

At least 847 records · Page 47Linked to original sources

Studies on regional blood flow of the mouse using whole-body autoradiography of 14C-iodoantipyrine.

In order to visualize regional blood flow in various tissues of the mouse at the same time, the distribution of radioactive carbon from 14C-iodoantipyrine was studied by whole-body autoradiography. The mice were frozen with Dry-Ice-hexane at 1, 10, 30 min, and 1 h and 3 h after intravenous injection of 14C-iodoantipyrine. Whole-sagittal sections of the frozen mouse, obtained by using a cryostat microtome, were dried in a cryostat and subjected to autoradiograhy. The resulting dry autoradiographs are called untreated autoradiographs in the present work. The sections were then fixed in cold 6% (w/v) HClO4, dried at room temperature and again subjected to autoradiography. Autoradiographs thus obtained are referred to as treated autoradiographs. It was found that the method could be suitable for the estimation of regional blood flow of the renal cortex, spleen, lung, skeletal muscle, bone marrow, thymus, testes, and brain.

Animals↗

The pathogenesis of abnormal cytoarchitecture in the cerebral cortex and hippocampus of the mouse treated transplacentally with cytosine arabinoside.

Pregnant mice were treated with cytosine arabinoside on days 13.5 and 14.5 of pregnancy. Brains of the offspring were studied histologically. The matrix layer of the embryonic brains was extensively destroyed 12 h after the injection of cytosine arabinoside, but regenerated partially on day 17 of gestation. In the cerebral cortex of 1-, 3-, and 5-day-old treated mice, abnormal clusters of young neurons were found on the surface of the developing cerebral cortex. Some clusters still had a supply of immature neurons from the remnants of the regenerated matrix layer. After 20 days, the clusters became gradually indistinct, although some vestigial groups of neurons were observed even after 120 days. In the hippocampus of young mice, the pyramidal cells decreased in number and were disarranged. Heterotopic pyramidal cell masses were found in the stratum radiatum and in the molecular layer of the dentate gyrus. Apical dendrites of pyramidal cells exhibited abnormal arborization. It was demonstrated by 3H-thymidine autoradiography that young neurons in the abnormal clusters in the cerebral cortex were those produced in the matrix layer regenerated after the destructive change by cytosine arabinoside.

Abnormalities, Drug-Induced↗

Intracellular redox state and control of gluconeogenesis in perfused chicken liver.

The role of the cellular redox state in the control of gluconeogenesis was studied in hemoglobin-free perfused chicken liver, by fluorimetric measurement of the redox states of intracellular pyridine nucleotides. The aminotransferase inhibitor, aminooxyacetate, completely inhibited gluconeogenesis from lactate in the perfused rat liver and to a small extent in the perfused chicken liver. In chicken liver, the highest rate of glucose production was seen with lactate, followed by fructose, pyruvate, and glycerol. When compared at 5 mM, the rate of glucose production from pyruvate was only 10% of that from lactate. Glucose production from a pyruvate/lactate mixture decreased with increasing proportions of pyruvate, together with redox changes of pyridine nucleotides to a more oxidized state. Increased reduction of pyridine nucleotides upon infusion of ethanol was associated with an increased glucose production from pyruvate, and the increase was abolished during octanoate infusion. This abolishment was accompanied by an increase in the acetoacetate to beta-hydroxybutyrate ratio with an oxidation of pyridine nucleotides. The octanoate-inhibited gluconeogenesis occurred at the higher lactate concentration (10 mM) with a transient oxidation of pyridine nucleotides. No significant inhibition was observed at 1 mM lactate, although an instant reduction of pyridine nucleotides was taking place. The rate of beta-hydroxybutyrate generation during octanoate infusion was 2.2 times higher at 1 mM than at 10 mM lactate. The inhibitory effect of octanoate on glyconeogenesis was completely relieved by the addition of NH4Cl. The results demonstrate that the regeneration of NADH in the cytosol is limited in chicken liver, and that gluconeogenesis is regulated, in part, by alteration in the redox states of mitochondria and cytosol.

Ammonium Chloride↗

Stimulation of gluconeogenesis by glucagon and norepinephrine in the perfused chicken liver.

The effects of glucagon and norepinephrine on gluconeogenesis by perfused chicken liver were studied with fluorimetric monitoring of the redox states of the intracellular pyridine nucleotides. Glucagon stimulated glucose production from precursors entering the pathway both above and below the level of triose phosphates without causing a detectable effect on the redox states of pyridine nucleotides. Glucagon stimulation was not abolished by subsequent infusion of octanoate or ethanol. The presence of a pyruvate/lactate mixture plus NH4Cl resulted in a maximum efficacy of glucagon. Glucose production from lactate and fructose was stimulated by norepinephrine. Norepinephrine always caused a change towards increased reduction of pyridine nucleotides with an increase in the beta-hydroxybutyrate/acetoacetate ratio, but displayed no stimulation of glucose and lactate production from pyruvate. As a result of octanoate infusion with lactate, the changes induced by norepinephrine were reversed. The responses to norepinephrine and phenylephrine were decreased markedly in liver perfused with a calcium-free medium and/or with phentolamine. Infusion of calcium into the calcium-deficient liver caused an abrupt elevation of glucose production together with a reduction of pyridine nucleotides, and the original response to norepinephrine was recovered. The results demonstrate that the effects of glucagon and norepinephrine on gluconeogenesis are not identical, and that norepinephrine stimulation is mediated through an alpha-adrenergic and calcium-dependent mechanism in which redox changes of mitochondrial pyridine nucleotides are involved.

Animals↗

[Plasma corticosterone concentration in morphine-dependent rats].

The effects of morphine on plasma corticosterone concentration in rats were studied using the drug-admixed food method. Morphine was mixed with the powder form of rat food in concentrations of 0.5 mg/g, 1 mg/g, and 2 mg/g of food. Plasma corticosterone concentration in rats treated with morphine-admixed food increased significantly, and the increment depended on the morphine concentration of drug-admixed food. The time course change of plasma corticosterone concentration in rats treated with morphine-admixed food (1 mg/g food) for 1 week was similar to that of non-treated rats without the concentration at 9:00. The plasma corticosterone concentration of morphine-treated rats at 9:00 was significantly increased in comparison with that of non-treated rats. Furthermore, the plasma corticosterone concentration after withdrawal in morphine-treated rats increased with time, and a significant increment in corticosterone was observed at 24 hr after the withdrawal. Naloxone, injected subcutaneously into morphine-dependent rats, significantly increased plasma corticosterone concentration. Increment of plasma corticosterone concentration in rats treated with morphine-admixed food for 3 or 4 weeks was significantly different from the non-treated group. The increment of plasma corticosterone concentration after the withdrawal was in a morphine treatment period-related manner. By these results, we suggest that tolerance to the increment action in plasma corticosterone concentration of morphine does not develop for at least 4 weeks using the drug-admixed food method, and the drug-admixed food method could induce morphine dependence without disturbance of the circadian rhythm in plasma corticosterone.

Animals↗

Ultrastructural study of biopsy specimens of rectal mucosa. Its use in neuronal storage diseases.

Rectal mucosa biopsy specimens from patients with neuronal storage diseases were examined by electron microscopy. The diseases were Tay-Sachs disease, Sandhoff's disease, Niemann-Pick disease types B and C, late infantile metachromatic leukodystrophy, GM1 gangliosidosis type 1, beta-galactosidase-neuraminidase deficiency, I-cell disease, and mucopolysaccharidoses (Hunter's syndrome and Sanfilippo's syndrome type A). Unmyelinated nerve fibers, endothelial cells, fibroblasts, plasma cells, and histiocytes were seen in the specimens. Except for plasma cells, the results thus obtained for various cells were similar to those obtained from skin and conjunctival biopsy specimens, which have been already reported. There has been no report so far on ultrastructure of the plasma cell in these diseases. Storage materials, eg, dense bodies and membrane-bound vacuoles, were observed in the plasma cells in various storage diseases, with the exception of late infantile metachromatic leukodystrophy. Thus, electron microscopy of rectal mucosa is useful in making diagnoses and examining plasma cells in some neuronal storage diseases.

Adolescent↗

Glucose uptake in mouse brain regions under hypoxic hypoxia.

Glucose uptake of individual structures within the brain was studied by dry-autoradiography with 2-deoxy-D-[14C(U)]glucose under mild hypoxic hypoxia (12% O2:88% N2 or 9% O2:91% N2 for 1 hr). Glucose consumption in the whole brain was estimated by combined gas chromatography-mass spectrometry (GC-MS). Mild hypoxia increased the optical density of the autoradiograph in all regions. The deuterated G-6-P (Glucose-6-phosphate) synthesized from deuterated glucose decreased significantly with 9% O2 hypoxia (P less than 0.05). The ratio of the deuterated G-6-P to deuterated glucose, a more appropriate indicator of glucose utilization than the concentration of deuterated G-6-P, decreased significantly with 12% O2 hypoxia (P less than 0.01). The hippocampus, white matter, colliculus superior, and corpus geniculatum laterale appeared to be particularly sensitive to hypoxia.

Anaerobiosis↗

Alteration of acetylcholine synthesis in mouse brain cortex in mild hypoxic hypoxia.

Acetylcholine synthesis in four brain regions (cerebral neocortex, hippocampus, septum and striatum) of the mouse during mild hypoxic hypoxia was measured by using [U-14C]glucose and [2H4]choline. At the same time, concentrations of norepinephrine and dopamine in four brain regions (cerebral neocortex, hippocampus, striatum and hypothalamus) were also estimated. During 12% O2 hypoxia, concentrations of acetylcholine in the striatum were significantly decreased (P less than 0.05), whereas [2H4]acetylcholine, lactate and glucose did not alter in any regions studied. During 12% O2 hypoxia, concentrations of choline and [2H4]choline were significantly increased in all regions examined (P less than 0.05), except the [2H4]choline inthe striatum. Radioactivity (dpm/100 mg protein) and specific activity (dpm/nmol) of acetylcholine were significantly decreased in the cerebral neocortex, hippocampus and septum (P less than 0.01) during 12% O2 hypoxia. A particularly marked decrease was found in the hippocampus, strongly suggesting that cholinergic terminals are particularly sensitive to hypoxia. In addition, these data also suggest that the acetylcholine synthesis from glucose might be more sensitive to hypoxia than that from choline. During 12% O2 hypoxia, concentrations of catecholamine did not alter in any regions examined, whereas during 9% O2 hypoxia dopamine was significantly decreased in the cerebral neocortex and hippocampus (P less than 0.05).

Acetylcholine↗

Electronmicroscopy of conjunctival biopsy in mannosidosis.

Electronmicroscopic examination was performed on conjunctival biopsies from two adolescent siblings with mannosidosis. Fibroblasts and endothelial cells contained membrane-bound vacuoles and vesicles that contained homogeneous osmiophilic globules. These vesicles seem to be pathognomonic of mannosidosis. Plasma cells also contained membrane-bound vacuoles, suggesting inhibition of the immunoglobulin production.

Adult↗

[Effect of alpha-methyl-para-tyrosine on "methamphetamine-induced sterotype and hypermotility" of reserpinized rats (author's transl)].

Previously we have found such "bizarre stereotypy" as persistent and bloody biting activity at the legs or the tail of himself or of the cage mate given methamphetamine (MAPT, 10 mg/kg) 24 hrs-48 hrs after long term-administration of reserpine (RE). The present investigation examined the effect of inhibition of dopamine synthesis in brain on MAPT-induced "bizarre stereotypy" and hypermotility of RE-treated rats. Male albino Wistar rats aged 4 weeks were injected intraperitoneally with RE (1.25 mg/kg) or 0.9% saline solution (1.25 ml/kg) every two days for 13 days. Twenty-two hrs after the last injection, rats received alpha-methyl-para-tyrosine ( alpha-MPT, 50 mg/kg, 125 mg/kg, 250 mg/kg i.p.) or its vehicle (1 ml/kg i.p.) and 2 hrs later, MAPT. MAPT induced continuous licking and biting at the metal wire of the cage floor in saline-treated rats and also "bizarre stereotypy" in RE-treated rats, but these activities were completely suppressed by pretreatment of alpha-MPT in each dose given (especially in 125 mg/kg, 250 mg/kg). Pertaining to the locomotor activities of saline-treated rats, the horizontal movements were especially enhanced by MAPT, however, the vertical movements remained unchanged. Alpha-MPT partially inhibited such horizontal movements while it potentiated the vertical movements. Locomotor activities of RE-treated rats were depressed one day after the last injection of RE, however, after the MAPT, these activities counts were increased considerably and were also higher in comparison to the counts of saline-treated rats given MAPT. These hypermotilities in RE-treated rats were partially antagonized by pretreatment with alpha-MPT. It is suggested that MAPT-induced "bizarre stereotypy" of RE-treated rats is mediated by the accelerative effect of RE on MAPT-induced dopamine synthesis, while MAPT-induced hypermotility of RE-treated rats is partially related to such an acceleration of dopamine synthesis.

Animals↗

Spontaneous stomach ulcer in genetically mast-cell depleted W/Wv mice.

Histamine has been implicated in the pathogenesis of gastroduodenal ulcers. Since mast cells contain a considerable amount of histamine as well as heparin and other biologically active substances, it seems reasonable to speculate that they are involved in this process. In fact, development of gastroduodenal ulcers was reported in dogs with mastocytoma, and an increase in mast-cell number was described in the vicinity of human gastroduodenal ulcers. Y.K. et al. have recently found that the number of mast cells in a unit length of the skin of W/Wv mutant mice is less than 1% of the value for the congeneic +/+ mice and that no mast cells are detected in the intestinal canal of W/Wv mice. Therefore, this mutant mouse was used to investigate the role of mast cells in the induction of gastroduodenal ulcers. As a preliminary experiment, we examined the stomach and duodenum of W/Wv mice without any treatments. Unexpectedly, we found the spontaneous development of perforating stomach ulcers in W/Wv mice, suggesting that mast cells do not necessarily have aggravating effects on the production of stomach ulcers.

Age Factors↗