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Biomedical subjects

Y Hirata

Publications and source records attributed to Y Hirata.

At least 145 records · Page 8Linked to original sources

Epidermal growth factor receptor is indispensable for c-Fos expression and protein synthesis by angiotensin II.

We have reported that angiotensin II induces the epidermal growth factor (EGF) receptor transactivation leading to extracellular signal-regulated kinase (ERK) activation in rat vascular smooth muscle cells. Here, we report that the EGF receptor kinase inhibitor AG1478 and the ERK kinase inhibitor PD98059 markedly inhibited angiotensin II-induced c-Fos expression and protein synthesis but not c-Jun expression in these cells. These data suggest that the EGF receptor transactivation and subsequent ERK activation are indispensable for angiotensin II-mediated growth promotion of vascular smooth muscle cells providing a new mechanistic insight whereby angiotensin II contributes abnormal vascular remodeling.

Animals↗

Kinetics of oxygen uptake at onset of exercise related to cardiac output, but not to arteriovenous oxygen difference in patients with chronic heart failure.

Patients with chronic heart failure performed exercise tests to evaluate the relation of kinetics of oxygen uptake to cardiac output and arteriovenous oxygen difference at the onset of exercise. The kinetics of oxygen uptake are primarily determined by cardiac output; these kinetics are useful in evaluating exercise intolerance and cardiac output response during exercise.

Adult↗

Structural Change in Dextran: Mechanism of Insolubilization by Adsorption on the Air-Liquid Interface.

To clarify the insolubilization mechanism of water-soluble dextran, the association of dextran in water was studied by dynamic light scattering measurements and a surface chemical approach. Dynamic light scattering measurements indicated that insolubilization of dextran is accompanied by a structural change in dextran. Surface tension data for dextran molecules revealed a structural change in dextran molecules at the air-liquid interface. These results suggest that insolubilization of dextran molecules occurred through an adsorption process at the air-liquid interface. Insolubilization of dextran molecules can be reduced by inhibition of this structural change in dextran molecules. The presence of boron as an impurity was found to trigger precipitation based on inductively coupled plasma mass spectrometry measurements and precipitation tests. Copyright 1999 Academic Press.

Journal Article↗

Musicians with absolute pitch show distinct neural activities in the auditory cortex.

Meg responses from musicians who had absolute pitch and from non-musicians were measured while they received different auditory stimuli. The parameters of single equivalent current dipoles (ECDs) were calculated for the N1m responses occurring in the auditory cortex. The location of the ECD for the noise burst was significantly posterior to the ECDs for the tones in the two hemispheres of the musicians, but not for those of the non-musicians. Further, in the left hemisphere the ECDs for the musicians were significantly posterior to those for the non-musicians. These results suggest distinct neural activities in the auditory cortex of musicians, which may be the result of cortical plasticity produced by training and/or an inherent cortical structural specificity.

Acoustic Stimulation↗

Molecular mechanisms of endothelin-1-induced cell-cycle progression: involvement of extracellular signal-regulated kinase, protein kinase C, and phosphatidylinositol 3-kinase at distinct points.

Although it is well established that endothelin-1 (ET-1) has not only vasoconstrictive effects but also mitogenic effects, which seem to be implicated in vascular remodeling, little is known about the molecular mechanisms by which ET-1 induces cell-cycle progression. In this study, we examined the effects of ET-1 on the cell-cycle regulatory machinery, including cyclins, cyclin-dependent kinase (cdk), and cdk inhibitors in NIH3T3 cells. ET-1 increased cyclin D1 protein (5.1+/-1.9-fold increase, 8 hours after stimulation, P<0.05), cdk4 kinase activity (2.8+/-0. 5-fold increase, 12 hours after stimulation, P<0.01), and cdk2 kinase activity (2.1+/-0.4-fold increase, 16 hours after stimulation, P<0.05) in a time- and dose-dependent manner. ET-1-induced increase in cyclin D1 protein, and cdk4 kinase activity was not significantly inhibited by an inhibitor of the mitogen-activated protein kinase kinase 1/2, PD98059, nor by the protein kinase C inhibitor calphostin C, whereas ET-1-induced upregulation of cyclin D1 protein and cdk4 kinase activity was significantly inhibited by the phosphatidylinositol 3-kinase inhibitor LY294002. In contrast, ET-1-induced activation of cdk2 kinase was significantly inhibited by PD98059, calphostin C, and LY294002. ET-1 increased 3H-thymidine uptake in a time-dependent fashion (0 hours, 4216+/-264 cpm per well; 8 hours, 5025+/-197 cpm per well; 16 hours, 9239+/-79 cpm per well, P<0.001 versus 0 hours). ET-1-induced increase in 3H-thymidine uptake was significantly inhibited by PD98059, calphostin C, and LY294002. These results suggest that ET-1-induced cell-cycle progression is, at least in part, mediated by the extracellular signal-regulated kinase, protein kinase C, and phosphatidylinositol 3-kinase and that those pathways may be involved in the progression of the cell cycle at distinct points.

3T3 Cells↗

Motor planning center for speech articulation in the normal human brain.

In order to locate the coordination center of speech movements in the dominant hemisphere of the normal human brain, we measured magnetoencephalographic (MEG) signals from the left frontal area of right-handed subjects while they pronounced different words. A broad response appeared during a period of 120-320 ms before the onset of speech sound, and its current dipole sources were localized on the magnetic resonance images in a region around the superior end of the left insula. Further, the onset of the MEG response preceded by about 100 ms the perioral muscle activities that occurred for the articulation in speaking the words. These results suggest that the deep frontal region is involved in the articulatory programming of speech movements.

Adult↗

Effects of hypertension, diabetes mellitus, and hypercholesterolemia on endothelin type B receptor-mediated nitric oxide release from rat kidney.

BACKGROUND: Although endothelin-1 is a potent vasoconstrictor peptide, stimulation of endothelin type B receptor (ETBR) causes bidirectional changes in vascular tone, ie, vasodilation and vasoconstriction. Roles of ETBR in pathological conditions are largely unknown. METHODS AND RESULTS: We studied the effect of BQ-3020, a highly selective ETBR agonist, on renal vascular resistance and nitric oxide (NO) release in the isolated, perfused kidney of rats with hypertension, diabetes mellitus, and hypercholesterolemia. Immunohistochemistry of endothelial NO synthase and ETBR was also examined. Infusion of BQ-3020 at concentrations of </=10(-10) mol/L reduced renal perfusion pressure in Dahl salt-resistant (R) rats but increased renal perfusion pressure in Dahl salt-sensitive (S) rats (10(-10) mol/L: -10.3+/-0. 6% versus 11.2+/-1.5%, R versus S; P<0.01). BQ-3020 caused a dose-dependent release of NO in both R and S rats, although the level of NO release in S rats was lower, as detected by chemiluminescence (10(-10) mol/L: 10.7+/-0.7 versus 3.1+/-0.4 fmol/min per gram of kidney, R versus S; P<0.01). Similar effects of BQ-3020 were observed in streptozotocin-induced diabetic rats and diet-induced hypercholesterolemic rats. Expression of endothelial NO synthase decreased in S rats but not in diabetic or hypercholesterolemic rats. In contrast, expression of ETBR in the endothelium was decreased in all 3 disease models compared with that in the vascular smooth muscle cell. CONCLUSIONS: These results suggest that impaired NO release in response to stimulation of ETBR is due, at least in part, to a decrease in endothelial ETBR and may play a role in vascular dysfunction usually associated with arteriosclerosis-related diseases.

Animals↗

Glucocorticoid-mediated suppression of the promoter activity of the cyclooxygenase-2 gene is modulated by expression of its receptor in vascular endothelial cells.

Cyclooxygenase-2 (COX-2), an inducible isozyme of cyclooxygenase, is expressed selectively in response to various inflammatory stimuli such as lipopolysaccharide (LPS) and its expression is suppressed by the glucocorticoid dexamethasone (DEX) in numerous types of cells. However, LPS-enhanced production of prostacyclin in bovine arterial endothelial cells (BAEC) was not significantly decreased by treatment with DEX but was suppressed by selective COX-2 inhibitors. This is consistent with the finding that DEX was not effective at preventing the expression of LPS-induced COX-2 mRNA. Transient transfection analysis showed that DEX did not suppress the LPS-induced promoter activity of the 5'-flanking region of the human COX-2 gene (nucleotides -327 to +59). Since RNA blot analysis indicated low-level expression of glucocorticoid receptor (GR) mRNA in BAEC, a GR-expression vector was transfected to evaluate the role of the GR in the COX-2 promoter activity. It was found that DEX mediated the suppression of the LPS-induced COX-2 promoter activity in a dose-dependent manner. These results suggest that the DEX-mediated suppression of LPS-induced promoter activity of the COX-2 gene is modulated by expression of the GR, which will be possible to account for a unique expression pattern of the COX-2 gene in BAEC.

Animals↗

Effect of inhaled nitric oxide on gas exchange in patients with congestive heart failure. A randomized, controlled trial.

BACKGROUND: Conventional vasodilators increase ventilation-perfusion mismatch and do not improve gas exchange even though they reduce pulmonary hypertension. However, the effects of nitric oxide inhalation on ventilatory and gas exchange values in patients with congestive heart failure are not known. OBJECTIVE: To investigate the effect of nitric oxide inhalation on gas exchange in patients with congestive heart failure. DESIGN: Randomized, controlled trial. SETTING: University hospital. PATIENTS: 16 patients with congestive heart failure (New York Heart Association class II or III). INTERVENTIONS: Patients inhaled nitric oxide gas at graded concentrations (n = 8) or were given intravenous isosorbide dinitrate, 2.5 mg (n = 8). MEASUREMENTS: Hemodynamic and ventilatory variables and blood gases were measured 5 minutes after inhalation of different doses of nitric oxide and 10 minutes after administration of isosorbide dinitrate. RESULTS: Nitric oxide inhalation reduced the mean pulmonary arterial pressure in a dose-dependent manner without altering the mean arterial pressure or cardiac output. At a dose of 40 parts per million, nitric oxide inhalation increased PaO2 (change from baseline, 12.0 mm Hg [95% CI, 2.3 to 21.7 mm Hg]; P = 0.014) and decreased the alveolar-arterial difference in partial pressure of oxygen (change, -8.6 mm Hg [CI, -16.8 to -0.4 mm Hg]; P = 0.038) and the ventilatory equivalent for carbon dioxide output (change, -6.7 [CI, -10.3 to -3.1]; P < 0.001). Although isosorbide dinitrate similarly decreased pulmonary arterial pressure, it did not alter gas exchange or ventilatory variables. CONCLUSIONS: Because nitric oxide inhalation improved gas exchange, it may be used as a supportive therapy when other conventional vasodilators worsen gas exchange.

Administration, Inhalation↗

The sarcoplasmic reticulum Ca2+-ATPase (SERCA2) gene promoter activity is decreased in response to severe left ventricular pressure-overload hypertrophy in rat hearts.

The sarcoplasmic reticulum Ca2+-ATPase (SERCA2) pump plays a key role in the contraction-relaxation cycle of the myocardium by controlling the intracellular Ca2+ concentration. SERCA2 protein and mRNA expression levels, as well as, SR Ca2+ uptake function are depressed in hypertrophied and failing myocardium. At this time, the molecular mechanisms regulating SERCA2 gene transcription during hypertrophy and heart failure are not completely understood, especially in vivo. Direct gene transfer into adult cardiac tissue has recently been shown to be a useful technique to study in vivo gene regulation. In this study, SERCA2 promoter-luciferase (Luc) reporter constructs of various lengths were injected into the beating left ventricular apex of adult rats (groups = compensated hypertrophy, heart failure, and controls) and the expression level was analysed. Our SERCA2 promoter analyses revealed three positive regulatory regions between -1810 bp and -1110 bp, -658 bp and -284 bp, and -267 bp and -72 bp and a negative regulatory region between -1110 bp and -658 bp, important for in vivo expression in rat hearts. SERCA2 promoter activity was also assessed in rat hearts with compensated pressure-overload hypertrophy (induced by the DOCA-salt treatment) and heart failure (induced by severe ascending aortic constriction). In the DOCA-salt-induced hypertrophy model, SERCA2 promoter activity was similar to that of sham controls. In contrast, severe constriction of the ascending aorta decreased the expression of the -1810 Luc and -1110 Luc constructs by 92.8% and 64.3%, respectively. This study suggests that only severe pressure-overload hypertrophy produces a significant decrease in SERCA2 promoter activity, and the promoter region extending to -1810 bp is sufficient for the down regulation of SERCA2 gene expression.

Animals↗

Scintigraphic demonstration of renal cell carcinoma with I-131-6beta-iodomethyl-19-norcholesterol: a case report.

Extraadrenal abnormal uptake on adrenocortical scintigraphy has been reported rarely in the normal gallbladder, lipid cell tumor of the ovary, or in clear cell type renal cell carcinoma. Clear cell type renal cell carcinoma contains glycogen and cholesterol like the adrenal gland, but the uptake of the radionuclide I-131 cholesterol has been reported to be low and not sufficient to image it. Right renal and adrenal masses were incidentally discovered on abdominal CT scan in a patient with chronic renal failure resulting in bilateral acquired cystic kidney disease. Adrenocortical scintigraphy done to know the nature of the adrenal mass showed high uptake corresponding to the right renal mass and the right adrenal mass. Clear cell type renal cell carcinoma and adrenal adenoma with prominent clear cells were histologically confirmed on hematoxylin-eosin stain and in an immunohistochemical study with renal cell antibody. Not only low-density lipoprotein receptors mediated uptake but also overall replacement of the right non-tumorous renal parenchyma by acquired cysts may have played a role in imaging the renal cell carcinoma on adrenocortical scintigraphy.

19-Iodocholesterol↗

Sigmoidofiberscopic incision plus balloon dilatation for anastomotic cicatricial stricture after anterior resection of the rectum.

We describe the procedure and examine the therapeutic efficacy of a combination of sigmoidofiberscopic incision plus balloon dilatation for tubular stricture by thick, long scar tissue at the colorectal anastomosis after anterior resection for rectal cancer. Balloon dilatation alone does not always relieve the strictures, although this method is the usual therapy for this condition. Five patients were identified in whom the stricture was not improved with balloon dilatation alone. Of these five patients, three complained of difficulty defecating, a feeling of incomplete evacuation, residual feces, and lower abdominal fullness. The remaining two patients, who had transverse colostomy to treat major leakage at the anastomosis, showed no symptoms. All five patients underwent the combination therapy described below. Two or three small radial incisions were made in the scar of the stricture with electrocautery under fiberscopic vision. Then the strictural scar was split and loosened bluntly along the incisions over a 15- to 20-minute period with a balloon dilator. This procedure was performed once or twice at a 2-week interval. In all five patients the stricture was improved according to objective criteria. There was also an improvement in the subjective symptoms suffered by three patients. The improvements were maintained over observation periods of 9 to 15 months. No complications were observed. Sigmoidofiberscopic incision plus balloon dilatation is an effective, safe therapy for cicatricial strictures after anterior resection for rectal cancer when the strictures have failed to improve following balloon dilatation alone.

Abdominal Pain↗

Tumors of peripheral nerves: correlation of symptoms, clinical signs, imaging features, and histologic diagnosis.

OBJECTIVE: To distinguish between benign and malignant tumors in the peripheral nerves. DESIGN AND PATIENTS: The clinical, imaging and histologic findings of 99 benign and 16 malignant tumors in the peripheral nerves were reviewed retrospectively. RESULTS: Preoperative motor weakness was observed in only six of 99 benign tumors and was mild, while slight to severe motor weakness was present in 15 of 16 malignant lesions. Pain at rest was present in five of 99 benign tumors and in 15 of 16 malignant tumors. All benign lesions showed a smooth tumoral margin, while half the malignant lesions showed an invasive margin on CT or MRI. Thirteen of 28 benign lesions on CT and nine of 23 on MRI showed round to geographic central enhancement, but this pattern was not seen in malignant lesions. CONCLUSION: Absence of severe motor weakness and a central enhancement pattern strongly suggest a benign nature, while severe rest pain and invasive tumor margin suggest malignant lesions in peripheral nerve tumors.

Adolescent↗

Insolubilization of water-soluble dextran.

In order to clarify the insolubilization mechanism of water-soluble dextran, comparison of water-soluble dextran and insoluble particles was carried out by detailed structural and surface chemical studies. The precipitate that form in bottled dextran solutions are composed of dextran itself, resulting from the interaction of dextran molecules (e.g., the formation of hydrogen bonds). Interaction of dextran molecules derived from a crystallized domain causes insolubilization from aqueous solution. In addition, the adsorption of dextran molecules on the air-liquid interface is the first step of insolubilization.

Calorimetry, Differential Scanning↗

High-level production of erythritol by strain 618A-01 isolated from pollen.

We have isolated a microorganism (strain 618A-01) from pollen which has the ability to produce erythritol when grown in the presence of glucose as the carbon source. When cultivated in a medium consisting of 20% glucose and 1% dried bouillon in a shake flask, 75 g/l erythritol was produced after 950 h, corresponding to a 37.5% yield against glucose consumption. No other polyols, including glycerol, were detected in the medium. Positive-ion fast atom bombardment mass spectrometry and 1H- and 13C-NMR analyses confirmed that the fermentation product was erythritol. Scanning electron microscopic analysis clearly demonstrated that the cells grown on YPD medium at 30 degrees C showed yeast-like morphology, while they appeared like hyphae at 37 degrees C. The complete 18S rRNA sequence of the isolate was determined, which showed high identity (99.5%) with the genus Ustilago of the phylum Basidiomycota. The data strongly suggest that strain 618A-01 belongs to the class Ustilaginomycetes. The culture conditions for the production of erythritol by the isolate were examined. The use of medium containing 1% tryptone, 0.5% yeast extract and 0.5% NaCl yielded the highest cell growth and erythritol productivity among the media tested. Continuous glucose feeding at 6-7% to the fermentor further increased the production of erythritol, and we obtained a maximal 100 g/l erythritol after 530 h, with a 39.3% yield.

Journal Article↗

Experimental demonstration and simulation of electrochemical non-linear responses to glucose and its interferents with an amperometric sensor.

A novel sensing system based on the multi-dimensional information contained in a dynamic non-linear response is proposed. A sinusoidal potential was applied to an amperometric-type glucose sensor and the resulting current of the sensor was analyzed by fast Fourier transformation (FFT). The amplitudes of the higher harmonics of FFT characterize the non-linear properties of the response. The amplitudes of the higher harmonics of FFT exhibit characteristic changes which depend on the concentration and the kinetics of the reactions of glucose and its interferents at the sensor surface. The essential features of the current-potential curve were reproduced by a computer simulation based on the kinetics of electrochemical reactions.

Electrochemistry↗

Hypoxia-induced adrenomedullin production in the kidney.

BACKGROUND: Adrenomedullin (AM) is a newly discovered peptide that has a potent vasorelaxant activity. To investigate its potential roles in hypoxia-induced renal injury, we examined whether AM production in the kidney increased under hypoxic conditions. METHODS: The AM transcript levels in Madin-Darby canine kidney (MDCK) cells, rat vascular smooth muscle cells (VSMCs), and rat mesangial cells were assessed by Northern blot analyses under normoxic and hypoxic conditions. The AM peptide in culture media was measured by radioimmunoassay. The effects of hypoxia on accumulation of cAMP in VSMCs were also examined. The stability of AM transcripts under normoxic and hypoxic conditions was compared in the presence of actinomycin D. The effects of hypoxia on AM promoter activity was assessed by transient transfection assays using the AM promoter subcloned upstream of luciferase gene. RESULTS: The expression of AM transcripts increased significantly in MDCK cells, rat VSMCs, and rat mesangial cells under hypoxic conditions without changes in the stability of AM transcripts; however, the AM promoter activity under hypoxic was not elevated significantly. The accumulation of AM peptide in culture media also increased significantly under hypoxic conditions in MDCK cells (2.2 +/- 0.1 fmol/10(5) cells in normoxia vs. 3.5 +/- 0.3 fmol/10(5) cells in hypoxia, 6 hr after hypoxia induction, P < 0.001), and in rat VSMCs (5.5 +/- 0.3 fmol/10(5) cells in normoxia vs. 7.8 +/- 0.4 fmol/10(5) cells in hypoxia, 8 hr after hypoxia induction, P < 0.01). Under hypoxic conditions, cAMP levels in rat VSMCs increased significantly compared with those under normoxic conditions (13.3 +/- 1.4 pmol/well vs. 4.6 +/- 0.4 pmol/well, P < 0.01). CONCLUSIONS: Renal parenchymal cells as well as renal vessels may produce AM under hypoxic conditions.

Adrenomedullin↗