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Biomedical subjects

S Miyata

Publications and source records attributed to S Miyata.

At least 145 records · Page 8Linked to original sources

Cerebrospinal fluid corticotropin-releasing hormone in neurodegenerative diseases: reduction in spinocerebellar degeneration.

Levels of corticotropin-releasing hormone (CRH) in cerebrospinal fluid (CSF) were examined in patients with spinocerebellar degeneration (SCD) including olivopontocerebellar atrophy (OPCA), dentatorubropallidoluysian atrophy (DRPLA) and Friedreich's ataxia, Parkinson's disease (PD) and senile dementia of the Alzheimer type (SDAT), and normal aged subjects. CRH concentrations in CSF were significantly reduced in SCD compared to SDAT, PD and CSF and normal aged subjects. It is likely that degeneration not only of the cerebral cortex and the limbic system but also of the subcortical structures such as the brainstem and the cerebellum alters levels of CRH in CSF. Together with the recent anatomical and physiological evidence, the results suggest pathophysiological relevance of CRH for the cerebellar symptoms in SCD.

Adult↗

Central mechanism of neural activation with cold acclimation of rats using Fos immunohistochemistry.

The expression of Fos protein in the rat diencephalon, brain stem, cerebellum, and spinal cord was investigated using immunohistochemistry during chronic cold exposure, in order to clarify the neural regions involved in the thermoregulatory responses and the central mechanism of neural activation with cold acclimation. Numerous Fos-positive cells were observed in many brain regions after cold exposure and changes in the number of Fos-positive cells were analyzed quantitatively. Fos-positive regions were classified into three groups on the basis of the expression period of Fos protein. The first group was where a significant number of Fos-positive cells were seen 3 h and 24 h after cold exposure, but not observed 14 days after exposure; the regions included the lateral septal nucleus (LS), parvocellular paraventricular hypothalamic nucleus (pPVN), posterior hypothalamic area (PH), supramammillary nucleus (SuM), locus coeruleus (LC), dorsal tegmental nucleus (DTg), vestibular nucleus (Ves), and nucleus of solitary tract (Sol). The second group was where a significant number of Fos-positive cells were found 3 h, 24 h and 14 days after cold exposure; the regions included the preoptic hypothalamic area (POA), paraventricular thalamic nucleus (PV), lateral preoptic area (LPO), zona incerta (ZI), subparafascicular thalamic nucleus (SPF), lateral dorsal central grey (CGLD), lateral ventral central grey (CGLV), microcellular tegmental nucleus (MiTg), lateral lemniscus nucleus (LL), dorsal parabrachial nucleus (DPB), and the cerebellum. The third group was where Fos-positive cells were more numerous 14 days after cold exposure than they were after 3 h and 24 h of exposure; these regions included the ventromedial hypothalamic nucleus (VMH) and the spinal cord. These results demonstrate that the numbers and regions of Fos-positive cells in the rat brains changed during chronic cold exposure, and such changes may reveal the cellular adaptation of the thermogenic responsive neurons in the rat brain to cold acclimation.

Adaptation, Physiological↗

Fos expression in the hypothalamic magnocellular neurons of rats during pregnancy, parturition and lactation.

Changes in Fos expression of magnocellular neurons in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) of the rat hypothalamus were investigated using immunohistochemistry during pregnancy, parturition and lactation. Quantitative morphometrical analysis revealed that Fos-positive cells in the hypothalamic magnocellular neurons were rarely seen in days 10 and 20 pregnant rats, however, significantly numerous Fos-positive cells were found in parturient rats. The number of Fos-positive cells was drastically decreased within a few days after parturition. Moreover, it was found using dual immunohistochemistry that the percentage of Fos-positive cells in vasopressin (AVP) magnocellular neurons of the SON was higher than that of the PVN in parturient rats, although oxytocin (OXT) magnocellular neurons showed the same percentage of Fos-positive cells between the SON and PVN. These results demonstrate that the hypothalamic magnocellular neurons express Fos during a limited period after parturition, and Fos expression in AVP magnocellular neurons is heterogeneous between the SON and PVN.

Animals↗

Microsatellite polymorphism between the tumor necrosis factor and HLA-B genes in Behçet's disease.

Behçet's disease is associated with the HLA-B51 antigen. However, it has not yet been clarified if the HLA-B51 gene itself is the susceptibility gene related to this disease or if it is some other non-HLA gene in linkage disequilibrium with HLA-B51. Therefore, we screened one of the HSP70 genes, HUM70t (HSP70-Hom), around the class III region and the microsatellite sequence located between the HLA-B and TNF genes for genetic polymorphism in BD. A comparison between patients with BD and healthy controls revealed no significant difference in the frequency of the HUM70t polymorphism. In the microsatellite sequence, Tau-a, in the region between the HLA-B and TNF genes, the frequency of 14 repetitions of GT was increased significantly and that of 11 repetitions was decreased significantly in the patient group. Further, the allelic distributions of the B51 antigen-associated microsatellite polymorphism differed significantly between patients and healthy controls, and in the B51 antigen-negative subjects, analysis of the microsatellite polymorphism also revealed a significant difference in the haplotype frequency between the patient and control groups. These results suggest that the HLA-B51 gene may not be the primary locus responsible for BD, and implicate some other gene(s) located between the TNF and HLA-B genes.

Base Sequence↗

Naloxone suppresses the rising phase of fever induced by interferon-alpha.

Interferon-alpha (IFN-alpha, 2.0 x 10(4) units) was bilaterally microinjected into the medial preoptic area and anterior hypothalamus in conscious rats treated 10 min prior with an opioid receptor antagonist, naloxone (NLX, 2 mg/kg, IM) or a prostaglandin synthetase inhibitor, acetaminophen (ACAP, 25 mg/kg, IM). The IFN-alpha-induced rise of rectal temperature (Tre) was suppressed from 20 to 60 min in NLX pretreated rats and from 30 to 180 min in ACAP pretreated rats. The rate of rise in Tre during the initial 20 min observed in NLX pretreated rats was significantly smaller than that in ACAP or saline pretreated rats. ACAP suppressed the fever when it was given 50 or 100 min after injection of IFN-alpha. In contrast, NLX did not affect the fever when given 25 or 50 min after IFN-alpha. The results suggest that an opioid that its involvement may last only in the early phase of the fever, but not after the plateau has been reached.

Analysis of Variance↗

Temporal changes of c-fos expression in oxytocinergic magnocellular neuroendocrine cells of the rat hypothalamus with restraint stress.

The present experiments were undertaken to examine c-fos expression in magnocellular neuroendocrine cells (MNCs) of the rat hypothalamus with restraint stress using dual immunohistochemistry for c-fos and oxytocin. Restraint stress induced c-fos expression in oxytocinergic MNCs in the supraoptic nucleus (SON) and paraventricular nucleus (PVN). Quantitative immunohistochemical analysis revealed that percentages of c-fos-positive cells to oxytocin-immunoreactive MNCs in the SON and PVN maximally increased at 2 h after restraint stress had started, and began to decline in spite of the fact that the restraint of animals were continued. Similar results were obtained from time course of c-fos expression in parvocellular neurons of the PVN. When animals were released to move freely in their home cages following the 3-h restraint, the plasma levels of oxytocin declined to reach basal levels within 30 min and c-fos immunoreactivity in the hypothalamic MNCs and parvocellular neurons disappeared faster than those of the continually restrained. These results demonstrate that restraint stress induces c-fos expression in oxytocinergic MNCs in the SON and PVN, and that time course of c-fos expression is transient even in the continuation of restraint stress.

Animals↗

Maintenance of ultrastructural plasticity of the hypothalamic supraoptic nucleus in the ovariectomized rat.

In the present experiments, we examined the effect of ovariectomy on the increases in litter weight and structural plasticity of MNCs in the supraoptic nucleus (SON) during lactation. Female rats were ovariectomized 2 days after parturition, and the increases in litter weight were measured as the index of milk let-down from dams during lactation. The lactation period was elongated up to 6 weeks by providing new litter to obtain more apparent effects of the ovariectomy. There was no significant difference in the increases in litter weight between non-operated and ovariectomized females. After lactation for 6 weeks, the ultrastructures such as juxtaposition (surface membrane apposition) and multiple synapses (terminals contacting with two or more postsynaptic elements) of MNCs in the SON in nonoperated and ovariectomized females were examined to compare with those of virgins. The percentage of juxtaposition and the number of multiple synapses significantly increased in nonoperated lactating females as compared with those of virgins. Ovariectomized rats showed similar structural changes to those of nonoperated females during lactation. Therefore, we conclude that ultrastructural plasticity of MNCs in the SON is maintained even in the absence of an ovary, and direct or indirect actions of suckling stimulation may be important in maintaining the plasticity during lactation.

Animals↗

Differences in Fos expression in the rat brains between cold and warm ambient exposures.

Fos expression in the rat diencephalon, brain stem, cerebellum, and spinal cord was examined after warm (33 degrees C) and cold (10 degrees C) ambient exposures. Fos expression was examined with use of immunohistochemical method and the number of Fos-positive neurons in each nucleus was quantitatively analyzed. When rats were exposed to cold ambient, significant number of Fos-positive neurons was found in the lateral septal nucleus (LS), preoptic hypothalamic area (POA), parvocellular paraventricular hypothalamic nucleus (pPVN), lateral preoptic area (LPO), zona incerta (ZI), paraventricular thalamic nucleus (PV), ventromedial hypothalamic nucleus (VMH), subparafascicular thalamic nucleus (SPF), posterior hypothalamic area (PH), supramammillary nucleus (SuM), microcellular tegmental nucleus (MiTg), lateral lemniscus nucleus (LL), lateral dorsal central grey (CGLD), lateral ventral central grey (CGLV), dorsal parabrachial nucleus (DPB), locus coeruleus (LC), dorsal tegmental nucleus (DTg), vestibular nucleus (Ves), nucleus of solitary tract (Sol), spinal cord, and cerebellum. When animals were exposed to warm ambient, the numbers of Fos-positive neurons in the LS, POA, PV, LPO, and SuM were significantly increased to be equal to those of cold ambient. However, after warm ambient exposure the numbers of Fos-positive neurons in the DPB and spinal cord were increased but less than those of cold ambient, and those in the pPVN, VMH, ZI, SPF, PH, CGLD, CGLV, MiTg, LL, LC, DTg, Ves, Sol, and cerebellum were not significantly increased as compared with those of control or cold ambient. Abdominal temperature was not changed during cold ambient exposure, but the temperature was significantly increased during warm ambient exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A gene (sleC) encoding a spore-cortex-lytic enzyme from Clostridium perfringens S40 spores; cloning, sequence analysis and molecular characterization.

Antiserum was raised against a 31 kDa spore-cortex-lytic enzyme, which is released during germination of Clostridium perfringens S40 spores. Western blotting of dormant spore and vegetative cell fractions separated by SDS-PAGE indicated that the 31 kDa enzyme is spore-specific and that the enzyme in the dormant spore exists as a 36 kDa protein which has no cortex-lytic activity. A gene encoding the 31 kDa enzyme, sleC, was cloned into Escherichia coli using a synthetic oligonucleotide as a hybridization probe and the nucleotide sequence of the entire gene was determined. The N-terminal amino acid sequence of the 36 kDa protein was found in this reading frame, confirming that the 36 kDa protein is a pro-form of the 31 kDa enzyme. The deduced amino acid sequence indicated that the 31 kDa enzyme is produced as a precursor, comprising three portions; an N-terminal prepro-sequence (114 amino acid residues), a pro-sequence (35 amino acid residues) and a mature enzyme (289 amino acid residues). It is suggested that the 36 kDa pro-enzyme is non-covalently attached to the exterior of the cortex layer, and that the proform is processed to release the active enzyme during germination.

Amino Acid Sequence↗

[Pharmacological properties of chitosan-coated dialdehyde cellulose (chitosan DAC), a newly developed oral adsorbent (I). Effect of chitosan DAC in normal rats].

The effects of chitosan-coated dialdehyde cellulose (chitosan DAC), a newly developed oral adsorbent of urea and ammonia, were examined in an in vitro adsorption study and in normal rats. Chitosan DAC showed high adsorption capacity for urea and ammonia in an in vitro study using the diluted supernatant of rat gastrointestinal fluid. In contrast, Kremezin, an oral charcoal adsorbent (AST-120), had little influence on these substances. In normal rats fed diets containing chitosan DAC (1, 2, 3, 4, 5, 7, and 10% content) for three weeks, increases in fecal wet weight, fecal dry weight and fecal water content were observed in a dose-dependent manner. In addition, chitosan DAC feeding increased fecal excretion of nitrogen and electrolytes (sodium, potassium and chloride ions) and decreased the apparent protein ratio in a dose-dependent manner. There were no obvious effects in serum parameters except that increased levels of protein and albumin and decreased levels of blood urea nitrogen, cholesterol and glucose were observed in rats fed a high concentration of chitosan DAC. In conclusion, these findings suggest the possibility that chitosan DAC treatment might be effective for improving chronic renal failure.

Administration, Oral↗

[Pharmacological properties of chitosan-coated dialdehyde cellulose (chitosan DAC), a newly developed oral adsorbent (II). Effect of chitosan DAC on rats with chronic renal failure induced by adriamycin].

The effects of chitosan-coated dialdehyde cellulose (Chitosan DAC), a newly developed oral adsorbent of urea and ammonia, were examined in rats with progressive chronic renal failure (CRF) induced by adriamycin. CRF rats induced by repeated injections of adriamycin were fed a diet containing chitosan DAC (5% content) or Kremezin (5% content), an oral charcoal adsorbent (AST-120) under strict paired-feeding for four months. CRF rats that received both a normal diet and Kremezin showed progressive azotemia, hyperphosphatemia, hyperlipidemia, proteinuria, and anemia, and began to die from 9 weeks after feeding started. In contrast, chitosan DAC-treatment showed marked prolongation of the survival period and decreases in blood urea nitrogen, serum creatinine, and serum phosphate. In addition, chitosan DAC-treatment ameliorated anemia in CRF rats, although hyperlipidemia and proteinuria were not improved. Furthermore, fecal weight, fecal water content, fecal nitrogen and fecal sodium were markedly increased, and the apparent protein ratio was decreased in CRF rats fed a diet containing chitosan DAC for 9 weeks. In contrast, none of these effects were observed in CRF rats receiving Kremezin. These observations suggest the further possibility of using oral adsorbent therapy for CRF patients.

Administration, Oral↗

Polymorphic distribution and molecular diversification of mitochondrial plasmid-like DNAs in the genus Oryza.

Four kinds of circular plasmid-like DNA, designated B1, B2, B3 and B4, have been found in the mitochondria of rice (Oryza sativa L.). We analyzed the distribution of families of plasmid-like DNAs homologous to those of O. sativa in 40 strains of the genus Oryza with AA, BB, BBCC, CC, CCDD and EE genomes. Plasmid-like DNAs were observed only strains having AA, CC and CCDD genomes. The distribution patterns of strains with AA genome were highly polymorphic. We amplified the plasmid-like DNAs from strains with the AA genome by PCR and examined restriction fragments length polymorphisms (RFLPs). RFLPs were detected among families of plasmid-like DNA amplified from different strains. This result indicated that some mutations, such as base substitutions and the insertion or deletion of a small fragment of DNA, had occurred and had accumulated during the differentiation of strains with an AA genome.

Base Sequence↗

Mitochondrial plasmid-like DNAs of the B1 family in the genus Oryza: sequence heterogeneity and evolution.

Four kinds of circular plasmid-like DNA, designated B1, B2, B3 and B4, have been found in the mitochondria of Oryza sativa L. with an AA genome. Three novel B1-homologous mitochondrial plasmid-like DNAs, designated, M1, M2 and M3, were isolated in the present study from strains with CC and CCDD genomes in the genus Oryza. We cloned and sequenced these DNAs and found that the sequences of these molecules have wide regions of homology. B1, M2 and M3 each lack about 300 bp of a region that is present in M1 and small repeats were found at the sites of deleted sequences. Therefore, we propose the hypothesis that the B1 family differentiated from a common ancient molecule that was similar to M1 via, probably, slipped mispairing during DNA replication at several stages in the evolution in the genus Oryza.

Base Sequence↗

Purification and partial characterization of a spore cortex-lytic enzyme of Clostridium perfringens S40 spores.

A spore cortex-lytic enzyme was purified in an active form from the exudate of fully germinated spores of Clostridium perfringens S40. The enzyme caused attenuation of absorbance in coatless spore suspensions and phase-darkening of the spores, but had minimal activity on isolated peptidoglycan fragments. The enzyme was identified as a 31 kDa protein which is probably an N-acetylmuramyl-L-alanine amidase. The amino-terminal 15 residues of the enzyme were: VLPEPVVPEYIVVHN.

Amino Acid Sequence↗

The role of renal dopamine in the reduction of high blood pressure by beta 1-selective beta-blocker with intrinsic sympathomimetic activity in spontaneously hypertensive rats.

The present experiments were undertaken to clarify the difference of renal dopamine production from beta 1-selective beta-blocker with and without intrinsic sympathomimetic activity (ISA). Either beta-blocker with ISA, celiprolol (100 or 300 mg/kg/day; CEL-100 or CEL-300) or beta-blocker without ISA, atenolol (50 mg/kg/day; ATE-50) was administered to the SHR from 19 to 26 weeks. Degrees of lowering blood pressure in CEL-300 SHR and in ATE-50 SHR were similar, but decrease in heart rate was significantly less in CEL-300 SHR than in ATE-50 SHR. Urine output, which was significantly less in control SHR than in control WKY, was significantly greater in CEL-100 SHR and CEL-300 SHR, but not in ATE-50 SHR. Urinary excretions of noradrenaline (u-NA) and dopamine (u-DA) were significantly higher in control SHR than in control WKY and a comparable u-DA/u-NA ratio was found in these two groups. U-DA and the ratio of u-DA/u-NA were significantly elevated in CEL-100 SHR and CEL-300 SHR, but not in ATE-50 SHR. There was a significant positive correlation between u-DA/u-NA ratio and urine output and a significant negative correlation between the ratio of u-DA/u-NA and change of blood pressure in control SHR, CEL-100 SHR and CEL-300 SHR. These results suggest that an enhancement of renal dopamine production by ISA (beta 2 stimulation) of beta 1-selective beta-blocker may contribute, at least in part, to the antihypertensive effect of this drug.

Adrenergic beta-1 Receptor Antagonists↗

Renal responses to atrial natriuretic peptide (ANP) in rats with non-oliguric acute renal failure induced by cisplatin.

This study was designed to compare the renal effects of atrial (A-type) natriuretic peptide (ANP) on control (saline-injected) rats and rats with non-oliguric acute renal failure induced by cisplatin. The results obtained here are summarized as follows: (1) In the metabolic cage study, cisplatin-treated rats showed increases in blood urea nitrogen and serum creatinine while creatinine clearance decreased to the lowest levels on day 4. A transient increase in urinary protein was observed at day 4. (2) ANP infusion significantly increased urine flow rate (UFR), creatinine clearance (CCr), fractional excretion rates of sodium (FENa) and chloride (FECl), and urinary phosphorus and magnesium (Mg) excretions in a dose-dependent manner without affecting renal plasma flow and fractional excretion rates of potassium and urea in cisplatin-treated rats. (3) Renal effects of ANP on UFR, CCr, FENa, FECl and excretion of Mg were more pronounced in cisplatin-treated rats compared to control rats although markedly blunted responses to ANP have been reported in nephrotic patients and nephrotic animals induced by adriamycin and aminonucleoside. (4) Histological examination showed extensive necrosis of the S3 segment of the proximal tubule located in the outer stripe of the outer medulla with minimal glomerular abnormalities in the kidney of cisplatin-treated rats. In conclusion, the main mechanism of the increased renal responses to ANP is considered to be due to an increased delivery of sodium, fluid and ANP itself to the inner medullary collecting duct which is the major renal site of action of ANP under the condition of acute proximal tubular necrosis by cisplatin.

Acute Kidney Injury↗

Cathepsin L-like protease from Xenopus embryos that is stimulated by nucleoside phosphates and nucleic acids.

An acid thiol protease that was activated at an early stage of embryogenesis was purified from Xenopus embryos. The N-terminal amino acid sequence (16 residues) of the heavy chain of the enzyme was similar to that of cathepsin L. The proteolytic activity of the protease was enhanced by ATP. Other nucleoside triphosphates, AMP and nucleic acids also enhanced the proteolytic activity. The possible mechanism and biological significance of the activation of the protease in Xenopus embryos are discussed.

Adenosine Triphosphate↗

Increase in 3-deoxyglucosone levels in diabetic rat plasma. Specific in vivo determination of intermediate in advanced Maillard reaction.

A specific assay of 3-deoxyglucosone (3-DG) was developed in our laboratory to help elucidate the relationship between advanced Maillard reaction and diabetic complications. 3-DG is known as a highly reactive intermediate of the reaction in vitro and a precursor of advanced glycosylation end products such as pyrraline and pentosidine, which have been previously detected in vivo. 3-DG was converted to a stable compound, 2-(2,3,4-trihydroxybutyl)-benzo[g]quinoxaline, by reacting with 2,3-diaminonaphthalene. Since the derivative had a characteristic UV spectrum, it was determined at 268 nm by high performance liquid chromatography. This method was sensitive enough to detect 10 ng/ml (61.7 nM) of 3-DG in vitro. A slight modification to this method allowed in vivo detection of small amounts of 3-DG. Plasma free 3-DG levels were significantly higher in streptozotocin-induced diabetic rats compared with controls (918 +/- 134 nM versus 379 +/- 69 nM, p < 0.001) and were suppressed with the administration of aminoguanidine, an inhibitor of Maillard reaction. Plasma pyrraline levels in diabetic rats also increased in parallel with elevated 3-DG levels but were only marginally suppressed by administration of aminoguanidine. Our results indicate that 3-DG is present in vivo under normal conditions and that its level increases in diabetic subjects. Determination of 3-DG represents a good tool to predict development and progression of diabetic complications and to assess the efficiency of inhibitors to Maillard reaction.

2-Naphthylamine↗