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Biomedical subjects

Y Nishida

Publications and source records attributed to Y Nishida.

At least 217 records · Page 12Linked to original sources

Dexamethasone-induced changes in glucose transporter 4 in rat heart muscle, skeletal muscle and adipocytes.

To clarify the effect of glucocorticoid on glucose transporters (GLUT) in adipocytes and muscle, we examined the changes of GLUT4 in rat heart muscle, skeletal muscle and adipocytes during long-term administration of dexamethasone and the translocation of GLUT4. The levels of GLUT4 in the plasma membrane and the low-density microsome fraction were measured by Western blotting using anti-GLUT4 peptide antibody. The levels of GLUT4 in the heart and skeletal muscles of rat were unchanged by treatment of dexamethasone. In the adipocytes the level of GLUT4 in plasma membrane was changed, but it was decreased in the low-density microsome fraction. Although adipocytes are less involved in blood sugar regulation than skeletal muscle, this finding suggests that glucose metabolism in Cushing's syndrome is affected partly by a decrease of GLUT4 in the adipocytes.

5'-Nucleotidase↗

Effects of thyroid hormone on coenzyme Q and other free radical scavengers in rat heart muscle.

Active oxygen species are reported to cause organ damage. This study was therefore designed to determine the behaviour of antioxidants and free radical scavengers so as to reveal changes in animals in the hyper- and hypothyroid state. Levels of antioxidant factors (i.e. coenzyme Q (CoQ)10, CoQ9 and vitamin E) and free radical scavengers (catalase, glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD)) were measured in the heart muscles of rats rendered hyper- or hypothyroid by 4 weeks of thyroxine (T4) or methimazol treatment. Serum levels of CoQ9 and total SOD were also measured. A significant reduction in CoQ9 levels was observed in the heart muscles of both hyper- and hypothyroid rats when compared with control hearts. There was no difference in serum CoQ9 levels in thyroid dysfunction when compared with control animals. Levels of vitamin E in the heart muscles of hyperthyroid rats were significantly increased, and there was no reduction in vitamin E levels in hypothyroid rats when compared with control hearts. GSH-PX levels in the heart muscle were reduced in hyperthyroid rats and increased in hypothyroid rats when compared with control hearts. However, there were no differences in catalase levels in heart muscle between hyper- and hypothyroid rats. The concentration of SOD in heart muscle was increased in hyperthyroid rats and was not decreased in hypothyroid rats compared with control rats, suggesting the induction of SOD by excessive production of O2-. These data suggest that the changes in these scavengers have some role in cardiac dysfunction in the hyper- and hypothyroid state in the rat.

Animals↗

Changes in calmodulin concentration and cyclic 3',5'-nucleotide phosphodiesterase activity in skeletal muscle of hyper- and hypothyroid rats.

Hyper- and hypothyroid states occasionally induce skeletal muscle dysfunction i.e. periodic paralysis and thyroid myopathy. The etiology of these diseases remains unclear, but several findings suggest that the catecholamine-beta-receptor-cAMP system or other messenger systems are disturbed in these diseases. In this context, we evaluated changes in the cyclic 3',5'-nucleotide metabolic enzyme, cyclic 3',5'-nucleotide phosphodiesterase (PDE) and calmodulin concentrations in skeletal muscles of hyper- and hypothyroid rats. Activities of cyclic AMP-PDE were low in skeletal muscle both from hyper- and hypothyroid rats, and calmodulin concentration was high in hyperthyroid and low in hypothyroid rats, as compared with normal rats. DE-52 column chromatographic analysis showed that the cGMP hydrolytic activity in peak I and the cAMP hydrolytic activity in peak II were decreased in hypothyroid rats, whereas cAMP hydrolytic activity in peak III was unchanged. The cAMP hydrolytic activity in peak III was decreased in hyperthyroid rats, but the activities in peaks I and II were unchanged. These findings indicate that cAMP and calmodulin may have some role in skeletal muscle function in the hyperthyroid state, and that cAMP and calmodulin-dependent metabolism may be suppressed in the hypothyroid state.

3',5'-Cyclic-AMP Phosphodiesterases↗

Changes in lipid peroxidation and free radical scavengers in the brain of hyper- and hypothyroid aged rats.

To determine how lipid peroxides and free radical scavengers are changed in the brain of hyper- or hypothyroid rats, we examined the behavior of lipid peroxide and free radical scavengers in the cerebral cortex of aged (1.5 years old) rats that had been made hyper- or hypothyroid by the administration of thyroxine or methimazol for 4 weeks. Concentrations of catalase, Mn-superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were increased in hyperthyroid rats compared with euthyroid rats. Concentrations of total SOD, Cu,Zn-SOD and GSH-PX were increased but that of Mn-SOD was decreased in hypothyroid animals. There were no differences among hyperthyroid, hypothyroid and euthyroid rats in the levels of coenzymes 9 or 10. The concentration of lipid peroxides, determined indirectly by the measurement of thiobarbituric acid reactants, was decreased in hyperthyroid rats but not in hypothyroid rats when compared with euthyroid animals. These findings suggest that free radicals and lipid peroxides are scavenged to compensate for the changes induced by hyper- or hypothyroidism.

Animals↗

Glomerular localization of interleukin-6 suppressed by steroid mini-pulse therapy in an IgA nephropathy patient.

A 16-year-old female with IgA nephropathy harboring histologically active lesions was treated with steroid mini-pulse therapy. Immunohistochemical examination revealed a diffuse distribution of interleukin-6 (IL-6) in the renal biopsy tissue. After treatment, her clinical factors and renal function improved, and renal biopsy showed reduced histological lesions and disappearance of the IL-6 distribution. Immunohistological studies of cytokines, such as IL-6, may be useful for evaluating the therapeutic effects in IgA nephropathy.

Adolescent↗

Role of endogenous opioids and central opioid receptors in cerebral cortical blood flow autoregulation.

To examine the role of endogenous opioids in autoregulatory maintenance of cerebral cortical blood flow (CoBF), CoBF was measured continuously by laser-Doppler flowmetry during changes in arterial pressure. Experiments were conducted on pentobarbital sodium-anesthetized adult mongrel dogs. Mean arterial pressure (MAP) was decreased or increased by inflating a perivascular occluder placed around the inferior vena cava or the thoracic descending aorta, respectively. To exclude the influence of the baroreceptor reflex on the autoregulatory maintenance of CoBF, all experiments were conducted on dogs with bilateral carotid sinus denervation plus vagotomy. CoBF was well maintained within its normal range despite large changes in MAP. Intravenous injection of naloxone (2.5 mumol/kg), an opioid receptor antagonist, significantly impaired the autoregulatory maintenance of CoBF during the decrease in MAP. On the other hand, intravenous injection of methyl naloxone (2.5 mumol/kg), which does not cross the blood-brain barrier, did not exert any significant effect on the MAP-CoBF relationship. Furthermore, intracerebroventricular injection of a smaller dose of naloxone (2.5 nmol/kg) significantly impaired the autoregulatory maintenance of CoBF during the decrease in MAP, as the larger dose of intravenous naloxone (2.5 mumol/kg) did. On the other hand, intravenous injection of the smaller dose of naloxone did not exert any significant effect on the MAP-CoBF relationship. These findings suggest that endogenous opioids and central opioid receptors may be partly involved in the CoBF autoregulatory mechanism. The endogenous opioids may modulate the autoregulatory vasodilation of the cerebral cortex during the decrease in MAP.

Animals↗

[Two-color flow cytometry analysis of lymphocyte subsets in patients with acute myocardial infarction and post-myocardial infarction syndrome].

Serial changes in lymphocyte subsets were analyzed in 37 patients with acute myocardial infarction (AMI), in 2 patients with postmyocardial infarction syndrome (PMIS), and in healthy subjects (control group) using two-color flow cytometry to investigate cellular immunity after AMI and PMIS. Peripheral blood lymphocyte subsets were measured on admission and at weeks 2, 4, 8, and 16 after the onset of AMI. The white blood cell count was significantly higher on admission and at week 2 in the AMI group compared with the control group. The percentage of CD4-positive helper T cells was significantly higher on admission and at weeks 2 and 4 in the AMI group compared with the control group, and the percentage of CD8-positive suppressor T cells was significantly lower in the AMI group at week 2 than in the control group. The ratio of helper-to-suppressor T cells peaked 2 weeks after the AMI and then decreased gradually. There were no significant changes in the CD4/CD8 ratio, the percentage of cytotoxic T cells, or the percentage of inducer T cells, throughout the observation period. There were no significant differences in the percentage of T cells, B cells, CD4-positive T cells, CD8-positive T cells, and natural killer cells between AMI patients and control subjects. The percentage of activated CD4- and CD8-positive cells was higher in the AMI group at weeks 4 and 8 than in the control group. There was no significant correlation between changes in lymphocyte subsets and infarct size. The percentage of activated CD8-positive cells was consistently higher in the PMIS group compared with the control and AMI groups. The percentage of cytotoxic T cells in one of the PMIS patients was significantly higher than in the AMI group. There were no significant differences in the proportions of other subsets between PMIS and AMI patients. The changes in lymphocyte subsets observed in patients with AMI suggested that immunological competence was enhanced in these patients. Abnormalities in humoral immunity, such as the appearance of anticardiac antibody, have been observed in patients with PMIS. Our results suggest that PMIS is also associated with changes in cellular immunity.

Adult↗

Role of homeodomain protein binding region in the expression of Drosophila proliferating cell nuclear antigen gene: analysis with transgenic flies.

The regulatory region of Drosophila proliferating cell nuclear antigen (PCNA) gene consists of a promoter region (-168 to +24 with respect to the transcription initiation site) and an upstream region containing three homeodomain protein binding sites (HDB) (-357 to -165). The PCNA gene regulatory regions with HDB (-607 to +137) or without HDB (-168 to +137) were fused with the lacZ and transgenic flies were established by P-element-mediated transformation. Male transgenic flies were crossed with wild-type females, and zygotic expression of the lacZ was monitored by quantitative beta-galactosidase assay, at various stages of development. Expression of the lacZ was high in embryos, first and second instar larvae, and adult females, and low at other stages of development. Only a marginal difference in expression was observed between flies carrying the homeodomain protein binding region and those not carrying it. Spatial pattern of the lacZ expression in the embryo visualized by immunostaining with the anti-lacZ antibody was similar to the distribution of the endogenous PCNA protein. Here, too, only a marginal difference was observed between transgenic flies carrying two different constructs of the PCNA lacZ. In genetic crossing experiments of transgenic flies with those carrying mutation in homeobox genes, no significant change in the lacZ expression pattern was observed. However, when male transgenic flies were crossed with female flies homozygous for a torso gain-of-function allele, repression of the lacZ expression was observed in the central region of the embryo. Because these local changes in the lacZ expression depend on the homeodomain protein binding region, unidentified homeodomain proteins are probably involved. Our results suggest that the promoter region is practically sufficient for expression of the PCNA gene and that the homeodomain protein binding region functions as a silencer when torso is activated ectopically.

Animals↗

[Endothelial dysfunction of the infarct-related coronary artery after reperfusion therapy].

The response of the infarct-related coronary artery to acetylcholine (20, 30, 50 micrograms) was investigated in 30 patients without restenosis during a 4-month follow-up period after direct percutaneous transluminal coronary angioplasty (PTCA) of the left proximal anterior descending coronary artery. The patients were divided into two groups according to wall motion as obtained by the centerline method from a left ventricular angiogram: moderate group (n = 10) with reduced wall motion with less than 20 abnormal contraction segments (moderate reduction at the infarcted site), severe group (n = 20) with reduced wall motion with 20 or more abnormal contraction segments (severe reduction). The acetylcholine-induced percentage changes in luminal diameter were assessed at the PTCA site and the distal portion of the coronary artery and the effect of acetylcholine was compared at the two sites. Coronary artery diameter in the moderate and severe groups displayed 8.1 +/- 24.9% and 7.4 +/- 30.8% contraction at the PTCA site and 38.3 +/- 46.3% and 72.5 +/- 28.2% contraction at the distal portion, respectively. Severe group had greater contraction at the distal portion than at the PTCA site. Vasoconstriction of the patent infarct-related coronary artery tended to occur in the infarcted area where wall motion was severely affected. In addition, endothelial dysfunction appears to be induced by a lengthy interruption of epicardial coronary blood flow and is present in the patent infarcted coronary artery without restenosis.

Acetylcholine↗

Enhanced neoplastic lesion development with adenine-induced experimental multicystic nephropathy by adenine--a model system for the analysis of renal tumor generation in long-term hemodialysis patients.

To cast light on the high incidence of renal cell tumors (RCT) in long-term hemodialysis patients, the role of background multicystic nephropathy was studied in a rat model. Group 1 animals were initially given N-ethyl-N-hydroryethylnitrosamine (EHEN) then subjected to adenine feeding until killing during weeks 20-27. Groups 2 and 3 received EHEN and adenine, respectively. All rats receiving adenine developed multicystic nephropathy. The incidence of renal cell hyperplasias (RCH) and multiplicities of both RCH and RCT in Group 1 were significantly increased as compared with Group 2, suggesting multicystic nephropathy provides favorable environment for tumor development.

Adenine↗

Identification of an alternative form of the Drosophila Ca2+/calmodulin-dependent protein kinase II that is maternally derived.

Four forms of the Drosophila Ca2+/calmodulin-dependent protein kinase II are generated from a single gene by alternative splicing (Ohsako et al. (1993) J. Biol. Chem. 268, 2052-2062). We identified a fifth form of the cDNA encoding the enzyme expressed in the ovary, unfertilized egg and early embryos by reverse transcription-polymerase chain reaction, which suggests that it is maternally derived. The fifth form was also generated from the gene by alternative splicing and was identical to the cDNA encoding the 530-amino-acid polypeptide, the longest of the four forms previously identified, except that it lacked exon 11. Three splicing derivatives which lost one amino acid from the 509- and 530-amino-acid polypeptides were also found in 4 to 10 h embryos.

Animals↗

Expression of myoglobin gene in skeletal muscle of patients with neuromuscular diseases.

Expression of the myoglobin (Mb) gene in skeletal muscle was studied in patients with Duchenne muscular dystrophy (DMD), polymyositis (PM), or amyotrophic lateral sclerosis (ALS) by measuring Mb concentration by radioimmunoassay and Mb messenger ribonucleic acid (RNA) (MbmRNA) levels by Northern blot analysis. Mb concentrations in the muscle cells (Mb/noncollagenous protein) were decreased in patients with DMD, PM, or ALS. However, while Mb concentrations per MbmRNA content (Mb/MbmRNA) were decreased in DMD and PM patients, these values were normal in ALS patients. These results suggest that Mb synthesis is increased in muscles of DMD and PM patients, but is not sufficient to compensate for the excessive loss of Mb from the affected muscles, and that the synthesis is decreased in the muscles of ALS patients.

Adolescent↗

A case of Crohn's disease limited to the appendix, showing a portentous ultrasonographic finding.

A case of Crohn's disease limited to the appendix is reported. A preoperative ultrasonic study of the lower right abdomen revealed an interesting appearance that we named the "milky way sign." Microscopic findings in the resected specimen confirmed that the sign represented adipose tissue of the mesoappendix that had become involved by transmural inflammation. This seems to be highly suggestive of Crohn's disease.

Adipose Tissue↗

Identification of asynergic but viable myocardium in patients with chronic coronary artery disease by gated blood pool scintigraphy during isosorbide dinitrate and low-dose dobutamine infusion: comparison with thallium-201 scintigraphy with reinjection.

To evaluate the ability of low-dose dobutamine and isosorbite dinitrate (ISDN) gated blood pool scintigraphy (GBPS) and thallium SPECT with reinjection to identify viability in asynergic myocardium, both procedures were performed in 38 consecutive patients with chronic coronary artery disease and left ventricular dysfunction. Twenty-two of the 38 patients with successful revascularization were analyzed. GBPS was performed at the baseline and during continuous infusion of low dose dobutamine (5 micrograms/kg/min) and ISDN (2 micrograms/kg/min). Cine mode GBPS wall motion was scored from normal (0) to dyskinesis (4) semiquantitatively. Forty-seven of 110 segments with severe asynergy at the baseline were analyzed. Viability determined by GBPS was defined as wall motion score improvement by more than 1 grade. Thallium viability was defined as the segment with redistribution or fill in with severe initial perfusion defect. GBPS was 76.7% sensitive and 70.6% specific for predicting post vascularization wall motion improvement (p < 0.005). Of 47 segments with severe asynergy, concordance of judgement was obtained in 40 segments (85.1%), and reversibility was correctly diagnosed in 34 of 40 patients (85.0%), but thallium with reinjection correctly identified tissue viability in 6 of 7 segments with discordance between 2 studies. These data suggest that most cases of reversible asynergy (hibernating myocardium) respond to ISDN and dobutamine, suggesting the possibility of predicting improvement by revascularization, although some underestimation of tissue viability remained to be resolved. Thallium with reinjection is superior to low-dose dobutamine + ISDN GBPS for the assessment of myocardial viability.

Adult↗