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Biomedical subjects

M Takaoka

Publications and source records attributed to M Takaoka.

At least 73 records · Page 4Linked to original sources
PubMed1996

Hypothermia suppresses nitric oxide elevation during reperfusion after focal cerebral ischemia in rats.

We aimed to investigate effect of temperature on the jugular levels of nitric oxide (NO) at reperfusion after focal cerebral ischemia. Both nitrosyl hemoglobin (HbNO) (2.5 +/- 0.4 microM) and plasma nitrite plus nitrate levels (61 +/- 5 microM) in rats under normothermia (approximately 37 degrees C) after 30 min of reperfusion following 2 h of left middle cerebral artery occlusion were significantly high, compared with sham operated rats (1.3 +/- 0.1 microM, 40 +/- 4 microM, respectively). Both HbNO (1.5 +/- 0.3 microM) and nitrite plus nitrate levels (43 +/- 7 microM) under moderate hypothermia (approximately 32 degrees C) were significantly low, compared with normothermic rats. HbNO (2.8 +/- 0.8 microM) and nitrite plus nitrate levels (65 +/- 8 microM) under mild hyperthermia (approximately 39 degrees C) were not significantly high. These results firstly demonstrated that hypothermia suppresses the elevation in intrajugular NO after cerebral ischemia-reperfusion.

Animals↗
PubMed1996

ETA receptor-mediated role of endothelin in the kidney of DOCA-salt hypertensive rats.

Renal effects of FR139317, an endothelin ETA receptor antagonist, were examined using anesthetized normotensive and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The intravenous bolus injection of FR139317 (10 mg/kg) produced a slight decrease in mean blood pressure (MAP; -13%) in the control rats and this hypotension was accompanied by a moderate renal vasodilation (renal vascular resistance: RVR; -12%). In the DOCA-salt hypertensive rat, FR139317 had a more pronounced hypotensive effect (MAP; -26%) accompanied by a potent renal vasodilation (RVR; -33%). FR139317 significantly increased renal blood flow only in the DOCA-salt rats. In contrast, FR139317 produced a significant decrease in urine flow and urinary sodium excretion only in control rats. Northern blot analysis revealed that the renal prepro endothelin-1 (ET-1) mRNA level was significantly increased in DOCA-salt hypertensive rats. Thus, it seems likely that endogenous ET-1 is responsible for the maintenance of DOCA-salt-induced hypertension. We also suggest that at least in part, ET-1 and ETA receptors are involved in renal hemodynamic abnormalities in DOCA-salt-induced hypertension. The augmentation of renal ET-1 production may possibly have a function in the development and maintenance of DOCA-salt-induced hypertension.

Animals↗
PubMed1996

Plasmin stimulates expression of endothelin-1 mRNA and endothelin-1 release in vascular endothelial cells.

Incubation of cultured porcine aortic endothelial cells (ECs) with plasmin resulted in a significant and concentration-dependent increase in endothelin-1 (ET-1) release from the cells. This increasing effect was completely inhibited by aprotinin but not by tranexamic acid, thereby suggesting that the plasmin-induced stimulation of ET-1 release requires the catalytic site but not the lysine binding site, in plasmin molecule. Plasmin stimulated the expression of prepro ET-1 mRNA in ECs. Actinomycin D chase experiments suggested that enhanced stability of ET-T mRNA could not account for the above plasmin-induced stimulation. It is likely that plasmin potentiates the endothelial ET-1 production, probably by the stimulation of ET-1 gene transcription. It remains to be seen whether the endothelial ET-1 production is enhanced after the thrombolytic therapy.

Animals↗
PubMed1996

Endothelin-1 secretion from cultured vascular endothelial cells of DOCA-salt hypertensive rats.

The profile of endothelin-1 (ET-1) release from cultured vascular endothelial cells (ECs) obtained from deoxycorticosterone acetate (DOCA)-salt hypertensive rats, was examined and compared with that from normotensive sham rats. ET-1 release from ECs was increased in a time-dependent manner, and the level of DOCA-salt hypertensive rats was higher than that of sham rats. Incubation of ECs with transforming growth factor (TGF)-beta 1 or thrombin resulted in a significant increase in the ET-1 release, while FK409, a novel nitric oxide donor, produced a dose-dependent decrease in the release. In the case of ECs from DOCA-salt hypertensive rats, the potencies of TGF-beta 1- or thrombin-induced action was much less than that seen with sham rats, while the difference of reactivity to FK409 was not observed between ECs of DOCA-salt rats and sham rats. Thus, ET-1 production in ECs appears to be up-regulated in DOCA-salt hypertensive rats. In addition, there seems to be an abnormalities in the signaling pathway via TGF-beta 1- or thrombin-induced enhancement of ET-1 production in ECs of DOCA-salt hypertensive rats.

Animals↗
PubMed1996

Species-specific measurement of the second group of Dermatophagoides mite allergens, Der p 2 and Der f 2, using a monoclonal antibody-based ELISA.

BACKGROUND: The group 2 Dermatophagoides mite allergens, Der p 2 and Der f 2, were known to be highly crossreactive, and previous assays to measure Der p 2 and Der f 2 were not species-specific. OBJECTIVE: The aim of this study was to develop a monoclonal antibody-based ELISA (MoAb-ELISA) to species-specifically measure Der p 2 and Der f 2. METHODS: The MoAb-ELISA for Der p 2 and Der f 2 was performed using species-specific MoAbs for Der p 2 and Der f 2 and a biotinylated second MoAb which recognized a common epitope on both Der p 2 and Der f 2. RESULTS: The assay was highly species-specific, reproducible and sensitive. Thirty-two house dust samples were assayed by the MoAb-ELISA for Der p 2 and Der f 2 and by a previously reported radioimmunoassay for Der 2 with rabbit anti-Der 2 antibodies. The summed values for Der p 2 and Der f 2 by the MoAb-ELISA demonstrated a good correlation with the Der 2 values using the radioimmunoassay (r = 0.978). Furthermore, the proportion of the Der p 2 level in the total Der 2 level (Der p 2 divided by Der p 2 plus Der f 2) correlated well with that of the D. pteronyssinus mite number to the total Dermatophagoides mite number identified by species (r = 0.970). CONCLUSION: The MoAb-ELISA for Der p 2 and Der f 2, as well as that of Der p 1 and Der f 1, will be useful for the standardization of mite extracts and for the assessments of mite allergen exposure.

Animals↗
PubMed1996

Effects of the endothelin ETA-receptor antagonist FR139317 on development of hypertension and cardiovascular hypertrophy in deoxycorticosterone acetate-salt hypertensive rats.

We investigated the role of endothelin-1 (ET-1) in the development of hypertension and cardiovascular hypertrophy in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Two weeks after the start of DOCA-salt treatment, the rats were divided into two groups and were given FR139317 [(R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]- carbonyl]amino-4-methyl-pentanoyl]amino-3-[3-(1-methyl-1H-indolyl)] propionyl]amino-3-(2-pyridyl) propionic acid], a specific ETA-receptor antagonist, or its vehicle for 2 weeks. Uninephrectomized rats without DOCA-salt treatment served as controls. Vehicle-treated DOCA-salt rats developed marked hypertension after 4 weeks. FR139317 significantly suppressed the increase in systolic blood pressure with values averaging 163 +/- 8 mmHg (P < 0.05 vs DOCA-salt rats receiving vehicle, 195 +/- 9 mmHg). Morphological studies in the rats given the vehicle showed vascular medial hypertrophy, with a significant increase in the wall area and wall-to-lumen ratio. A marked decrease in vascular wall hypertrophy was observed in the FR139317-treated DOCA-salt rats. The cardiac hypertrophy in DOCA-salt hypertensive rats was also significantly reduced by FR139317. Therefore, these results suggest that ET-1 plays an important role in the development of DOCA-salt hypertension presumably by stimulating the ETA receptor. In addition, we found that an ETA-receptor antagonist effectively reduced cardiovascular hypertrophy in the rats, so the cardiovascular hypertrophy noted in DOCA-salt hypertensive rats may be related to ET-1.

Analysis of Variance↗
PubMed1996

Changes in urinary enzyme activity and histochemical findings in experimental tubular injury induced by gold sodium thiomalate.

To elucidate the renal injury induced by gold treatment, we administered various doses of gold sodium thiomalate (GST) to Wistar rats and investigated alterations in the urinary enzyme activity, gamma-glutamyl transpeptidase (gamma GTP) and N-acetyl-beta-glucosaminidase (NAG) activity, and histochemical change of enzymes, gamma GTP, alkaline phosphatase (ALP) and acid phosphatase (ACP) activity in the renal tissue. The single administration of a large dose of gold salts induced acute tubular necrosis and enzyme leakage was detected histochemically without damage to the glomerulus. After chronic administration of small doses of gold salts, the urinary gamma GTP activities gradually increased, but urinary NAG activities did not. These findings suggested that the change in urinary enzyme activities, which leaked from inside of brushborder or lysosome, indicated the degree or localization of tubular damage, because renal tubules were selectively injured by gold salts.

Acetylglucosaminidase↗
PubMed1995

Role of endothelin-1 in hypertension induced by long-term inhibition of nitric oxide synthase.

We examined the effect of long-term nitric oxide (NO) synthase inhibition on vascular and renal endothelin-1 levels and evaluated the antihypertensive effect of endothelin ETA receptor antagonist FR139317 ((R)2(-)[(R)-2(-)[(S)-2(-)[[1-(hexahydro-1H-azepinyl)]- carbonyl]amino-4-methyl-pentanoyl]amino-3(-)[3-(1-methyl-1H- indolyl)]propionyl]amino-3-(2-pyridyl) proprionic acid] on rats in which NO synthase was blocked. Chronic NO blockade was produced by oral administration of the NO synthase inhibitor NG-nitro-L-arginine for 4 weeks, which produced sustained hypertension. At the end of this time, there were no significant changes in aortic and renal immunoreactive-endothelin levels between NG-nitro-L-arginine-treated hypertensive rats and normotensive control rats. Intravenous injection of FR139317 (10 mg/kg), which had a sufficient hypotensive effect on deoxycorticosterone acetate-salt hypertensive rats, to NG-nitro-L-arginine-treated hypertensive rats produced only a moderate hypotensive effect, to the same degree as seen in normotensive rats. The results indicate that long-term NO synthase inhibition did not affect vascular and renal endothelin-1 levels in these rats. It seems likely that endothelin-1 and ETA receptors do not contribute to the sustained hypertension induced by NO synthesis blockade.

Administration, Oral↗
PubMed1995

Percutaneous transluminal angioplasty for severe stenosis of the posterior cerebral artery: case report.

The Stealth dilation catheter was used for the intravascular treatment of a patient who had hemodynamically significant stenosis of the posterior cerebral artery and had a history of recurrent transient ischemic attacks associated with right hemiparesis and ipsilateral hemianopia dating from March 1993. Cerebral perfusion studies prior to and after the intravenous administration of acetazolamide demonstrated regions of moderately low perfusion and low hemodynamic reserve in the territories of the left middle and posterior cerebral arteries. Cerebral angiograms demonstrated severe stenosis of the left posterior cerebral artery and occlusions of both middle cerebral arteries, which had leptomeningeal anastomoses with the posterior cerebral arteries. Percutaneous transluminal angioplasty (PTA) was performed using the Stealth catheter on the stenotic segment of the left posterior cerebral artery after left superficial temporal artery-middle cerebral artery anastomosis. The patient manifested marked improvement in her neurologic condition just after PTA, in association with marked increase in cerebral perfusion and hemodynamic reserve in the territories of the left middle and posterior cerebral arteries. We have presented evidence that PTA can be used to treat patients with stenosis of the first segment of the posterior cerebral artery and hemodynamic compromise in the territory that artery supplies.

Aged↗
PubMed1995

Age-related changes in the susceptibility to clofibric acid, a hypolipidemic agent, of male rat liver.

Age-related changes in the susceptibility to clofibric acid were investigated in male F344 rats of 8, 52, and 117 weeks old. Hepatomegaly, decrease of serum total cholesterol and triglyceride, increase of the total cytochrome P-450 contents, induction of the activities of microsomal omega-hydroxylation and peroxisomal beta-oxidation, proliferation of smooth endoplasmic reticulum and peroxisomes were detected in 8- and 52-week-old rats. In 117-week-old rats clofibric acid treatment resulted in decrease of serum total cholesterol, elevation of the activities of microsomal and peroxisomal enzymes, and slight proliferation of peroxisomes. These results suggest that the susceptibility of the male F344 rat liver to clofibric acid decreases in 117-week-old rats, though the effect is still recognizable.

Administration, Oral↗
PubMed1995

Role of endothelin-1 and the ETA receptor in the maintenance of deoxycorticosterone acetate-salt-induced hypertension.

1. To search for a possible role for endothelin-1 (ET-1) in deoxycorticosterone acetate (DOCA)-salt-induced hypertension, we examined changes in concentration of ET-1 in vascular and renal tissue in DOCA-salt hypertensive rats and evaluated the antihypertensive effect of the ETA receptor antagonist, FR139317. 2. There was an increase in aortic immunoreactive-ET (IR-ET) concentrations in association with hypertension-induced treatment. There were no significant changes in ET-1 levels in the kidney with DOCA-salt treatment. 3. In DOCA-salt hypertensive rats, a significant correlation (r = 0.83, P < 0.01) was found between aortic IR-ET concentrations and systolic blood pressure. 4. High-performance liquid chromatography analysis of the aortic extract from DOCA-salt rats revealed one major component corresponding to the elution position of synthetic ET-1. 5. The intravenous bolus injection of FR139317 (10 mg kg-1) produced a slight decrease in blood pressure in the control rats and in the DOCA-salt hypertensive rat, FR139317 had a more pronounced hypotensive effect. 6. We propose that ET-1 production in vascular tissues is increased in DOCA-salt hypertensive rats. In addition, our study indicates the pathophysiological importance of increased endogenous ET-1 in the maintenance of DOCA-salt-induced hypertension, through interaction of the peptide with ETA receptors.

Animals↗
PubMed1995

Effects of phosphoramidon on endothelin-1 and big endothelin-1 production in human aortic endothelial cells.

Using cultured human aortic endothelial cells, we examined the effects of phosphoramidon, an endothelin converting enzyme (ECE) inhibitor, on the release of endogenous endothelin-1 (ET-1) and big endothelin-1 (big ET-1), and on the generation of ET-1 from exogenously applied big ET-1. Phosphoramidon, at concentrations of 10(-6) to 2 x 10(-4) M, caused a biphasic alteration of the ET-1 release, i.e., at lower concentrations of the drug, there were slight but unexpected increases of the release, whereas higher concentrations led to a decrease which is due to the drug-induced inhibition of ECE. The former effect appears to be based on the inhibition of ET-1 degradation by neutral endopeptidase 24.11 (NEP), since kelatorphan, a specific NEP inhibitor, produced a similar increasing effect on ET-1 release. Phosphoramidon enhanced the big ET-1 release from the cells in a concentration-dependent manner. When high concentrations of phosphoramidon were added, there was a dramatic increase in the release of big ET-1, which cannot be explained only by the drug-induced inhibition of ECE. This increase in big ET-1 release appeared to be partly due to a transient stimulation of the expression of prepro ET-1 mRNA. The amount of ET-1 generated from exogenously applied big ET-1 was markedly decreased by phosphoramidon in a concentration-dependent manner. In a similar fashion, phosphoramidon markedly inhibited ECE activity of the membrane fraction of cultured cells. Thus, ET-1 generation from exogenously applied big ET-1 reflects the functional phosphoramidon-sensitive ECE activities in human aortic endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗
PubMed1995

Age-related changes in thyroid lesions and function in F344/DuCrj rats.

Age-related thyroid changes, such as those in weight, histology, morphometry, and hormonal concentrations were evaluated in 460 male and 460 female F344 rats from 9 to 109 weeks of age. The absolute weight of the thyroid increased with age in both sexes, but the relative weight was unaffected by age. Ectopic thymus and ultimobranchial cyst were observed in rats of both sexes from 9 to 109 weeks of age. The incidence of both congenital anomalies decreased with age. The incidence of follicular cyst, which was first observed in rats at 20 weeks of age, increased at 109 weeks. Hyperdistention of the follicle with infiltration of macrophages in the lumen and deposition of brown pigments in the cytoplasm of epithelial cells were observed in a few rats at 59 weeks of age. These follicular lesions were found in 29% of the males and 7% of the females at 109 weeks. The first thyroid tumor was seen at 59 weeks of age. In 109-week-old rats, 5% of males had follicular tumors, and 18% of males and 10% of females had C-cell tumors. At 82 weeks of age, the follicular area and the area of the follicular lumen increased, and the height of follicular epithelial cells decreased. Serum T3, T4 and TSH concentrations decreased with age and were significantly reduced at 82 weeks. These results suggest that in F344 male rats the thyroid structural and functional changes occurred with age, and thyroid function decreased after 82 weeks of age.

Aging↗
PubMed1995

Role of transforming growth factor-beta 1 on platelet-induced enhancement of endothelin-1 production in cultured vascular endothelial cells.

We and other investigators obtained evidence that platelets stimulate endothelin-1 (ET-1) production at both message and protein levels in vascular endothelial cells (ECs), and that platelet-derived transforming growth factor-beta 1 (TGF-beta 1) is responsible for this stimulation. In the present study, we examined the effects of acidification or heat treatment, known to activate latent TGF-beta 1, on the platelet supernatant-induced ET-1 production in cultured porcine aortic ECs. Supernatant of platelets (6.0 x 10(8) platelets/ml) aggregated by adenosine diphosphate contained large amounts of TGF-beta 1, but were almost in a latent form, and the proportion of active TGF-beta 1 in the supernatant was increased markedly in the case of acidification or heat treatment. These treatments also significantly potentiated the supernatant-induced stimulation of prepro ET-1 mRNA expression and the ET-1 release in ECs. Purified TGF-beta 1 also enhanced ET-1 release, dose-dependently, but the enhancement declined at the higher concentrations. Thus, powerful stimulation of ET-1 production by platelet supernatant after acidification or heat treatment cannot be explained only by increments in active TGF-beta 1. The supernatant-induced stimulation of ET-1 synthesis was significantly inhibited by concomitant treatment of TGF-beta 1 neutralizing antibody, but this inhibition was incomplete even at a concentration that abolished TGF-beta 1-induced maximal stimulation. These results suggest that platelet-induced stimulation and subsequent acidification and heat treatment-induced potentiation on endothelial ET-1 production depend closely on release and activation of TGF-beta 1 derived from platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Involvement of endothelin-1 in deoxycorticosterone acetate-salt-induced hypertension and cardiovascular hypertrophy.

The role of endothelin-1 (ET-1) in the development and maintenance of hypertension is controversial. To determine the role of ET-1, we investigated the possible involvement of ET-1 in the pathogenesis of experimental hypertensive rats. In deoxycorticosterone acetate (DOCA)-salt hypertensive rats, a significant increase in aortic immunoreactive ET (IR-ET) level was observed, compared with age-matched sham-operated rats. Intravenous injection of the ETA receptor antagonist FR139317 (10 mg/kg) produced a slight decrease in blood pressure in sham rats. In the DOCA-salt hypertensive rats, FR139317 had a more pronounced hypotensive effect. Treatment with the antagonist in nitro-L-arginine (LNA)-induced hypertensive rats, two-kidney, one-clip (2K1C) renal hypertensive rats, spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHR-SP) produced only moderate hypotensive effects, of the same degree as those in normotensive rats. Long-term treatment with FR139317 in DOCA-salt hypertensive rats efficiently suppressed the development of hypertension and cardiovascular hypertrophy. We propose that ET-1 production in vascular tissues is increased in DOCA-salt hypertensive rats. In addition, our study suggests the pathophysiologic importance of ET-1 and the ETA receptor in DOCA-salt-induced hypertension but not in SHR, in SHR-SP, in 2K1C renal hypertension, and in LNA-induced hypertension.

Animals↗
PubMed1994

The "turn-over" technique for selective cerebral angiography.

In older patients with severe aortic atherosclerosis or pronounced tortuosity of the brachiocephalic vessels, selective catheterisation may be impossible. In order to overcome this difficulty we introduced a new "turn-over" technique. This involves introduction of a long guidewire through the catheter, advancing it and turning it over just above the aortic valves and finally introducing it into each major vessel, followed by the catheter. Selective catheterisation was completely achieved with the turn-over technique in 13 patients. Turning over the catheter just above the aortic valves and introducing it into the vessels was very easy.

Aged↗