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Biomedical subjects

T Horio

Publications and source records attributed to T Horio.

At least 127 records · Page 7Linked to original sources
PubMed1995

Vascular dopamine-I receptors.

The modulation of dopamine DA1 receptors of cultured rat renal arterial smooth muscle cells by phorbol ester, glucocorticoid and sodium chloride was studied. The extent of [3H]Sch-23390 binding to phorbol ester-treated cell was increased without any change in the dissociation constant (Kd). At a concentration of 10 nmol/l, the synthetic glucocorticoid dexamethasone increased maximum receptor binding (Bmax) but had no effect on the Kd. 100 mmol/l sodium chloride did not change Bmax, but increased the Kd for DA1 receptor. The production of cAMP in response to DA1 receptor stimulation was enhanced without any change of the adenylate cyclase activity. The glucocorticoid effect on DA1 of arterial smooth muscle cells became apparent after hours of incubation in the presence of the steroid and was significantly inhibited by cycloheximide (10 micrograms/ml) and by the glucocorticoid receptor antagonist RU-38486, indicating that the effect required protein synthesis through glucocorticoid receptors. Treatment of cells with 1 mumol/l dexamethasone for 24 h increased basal and DA1-stimulated adenylate cyclase activity. Basal adenylate cyclase was decreased by sodium chloride in a dose-dependent manner. These results suggest differential control of DA1 receptors on vascular smooth muscle cells by protein kinase C, glucocorticoid or sodium chloride.

Adenylyl Cyclases↗
PubMed1995

Promotion of nitric oxide formation by heparin in cultured aortic endothelial cells from spontaneously hypertensive rats.

1. The present study examined the effect of heparin on nitric oxide (NO) formation and cyclic guanosine 3', 5'-monophosphate (cGMP) levels in cultured aortic endothelial cells (EC) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. 2. Bradykinin (BK), adenosine diphosphate (ADP), Ca2+ ionophore A23187 (Io) and endothelin-3 (ET-3) stimulated the production of NO and cGMP. No significant difference was observed in both NO and cGMP production in EC between WKY and SHR. 3. Heparin enhanced BK-, ADP-, Io- and ET-3-stimulated NO and cGMP production. These enhancements by heparin in EC were significantly greater in SHR than in WKY. 4. Both NO formation and cGMP production stimulated by the agonists and/or heparin were blocked in the presence of NG-monomethyl-L-arginine (LNMMA, 10(-5) mol/L). 5. Increased sulphur level was observed on heparin-treated SHR EC surface compared with that on control SHR EC or on heparin-treated WKY EC surface. 6. These results suggest that heparin promotes agonist-induced NO-cGMP response in cultured EC from SHR.

Animals↗
PubMed1995

Promotion of nitric oxide formation by heparin in cultured aortic endothelial cells from spontaneously hypertensive rats.

1. The present study examined the effect of heparin on nitric oxide (NO) formation and cyclic guanosine 3', 5'-monophosphate (cGMP) levels in cultured aortic endothelial cells (EC) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. 2. Bradykinin (BK), adenosine diphosphate (ADP), Ca2+ ionophore A23187 (Io) and endothelin-3 (ET-3) stimulated the production of NO and cGMP. No significant difference was observed in both NO and cGMP production in EC between WKY and SHR. 3. Heparin enhanced BK-, ADP-, Io- and ET-3-stimulated NO and cGMP production. These enhancements by heparin in EC were significantly greater in SHR than in WKY. 4. Both NO formation and cGMP production stimulated by the agonists and/or heparin were blocked in the presence of NG-monomethyl-L-arginine (LNMMA, 10(-5) mol/L). 5. Increased sulphur level was observed on heparin-treated SHR EC surface compared with that on control SHR EC or on heparin-treated WKY EC surface. 6. These results suggest that heparin promotes agonist-induced NO-cGMP response in cultured EC from SHR.

Animals↗
PubMed1994

Phototoxicity and photoallergenicity of quinolones in guinea pigs.

Clinical reports indicate that the fluoroquinolone group of antibiotics can induce cutaneous photosensitivity reactions. In the present study, phototoxicity and photoallergenicity of quinolones including nalidixic acid (NA) norfloxacin (NFLX), ofloxacin (OFLX), enoxacin (ENX), ciprofloxacin (CPFX), lomefloxacin (LFLX), and tosufloxacin (TFLX) were experimentally examined in an in vivo system using the guinea pig. Phototoxicity of all quinolones tested was demonstrated after a single, oral administration of the drugs and subsequent exposure to long-wave ultraviolet (UVA) at a dose of 30 J/cm2. The phototoxic potencies were: ENX, LFLX > OFLX > NA, TFLX > NFLX, CPFX. Photoallergic reaction was also induced to LFLX and NA by pretreatment with cyclophosphamide, an immunoadjuvant. No cross-reactions in photoallergy were observed among quinolones. The photo-ingestion test was positive in photoallergically sensitized animals, while the photopatch test was negative. This is the first report which demonstrated experimentally the photoallergenicity of quinolones. Clinical features of the photosensitivity due to quinolones can be explained by the results of the present experiments.

4-Quinolones↗
PubMed1994

Cockayne syndrome in two adult siblings.

Although survival beyond the second decade is unusual in patients who have Cockayne syndrome, we describe two brothers with the syndrome who are 42 and 55 years of age. Their cultured skin fibroblasts showed extreme UV sensitivity but had almost normal UV-induced unscheduled DNA synthesis. The patients were classified as genetic complementation group B after study of the recovery of RNA synthesis after UV irradiation of fused cells. Clinical phototesting revealed a reduced threshold for UVB erythema.

Adult↗
PubMed1994

Heparin inhibits endothelin-1 production in cultured rat mesangial cells.

The present study was designed to examine whether heparin inhibits basal or stimulated endothelin-1 production by arginine vasopressin (AVP) and platelet-derived growth factor (PDGF) in cultured rat mesangial cells. In addition, the reversibility of the heparin effect on mesangial cell endothelin-1 production was examined. AVP and PDGF stimulated endothelin-1 secretion in a concentration-dependent manner in these cells. Heparin (10 to 100 U/ml) exhibited concentration-related inhibition of AVP- and PDGF-stimulated endothelin-1 secretion. Heparin also had weak but significant inhibitory effects on basal endothelin-1 secretion in these cells. The protein kinase (PKC)-activating phorbor ester, phorbor myristate acetate (PMA), stimulated endothelin-1 secretion and heparin inhibited PMA-stimulated endothelin-1 secretion. In addition, the inhibitory effect of heparin was completely abolished in PKC-depleted mesangial cells. Mesangial cells which were exposed to a high concentration (100 U/ml) of heparin for 24 hours were capable of producing endothelin-1 after a short lag period of removal of heparin from the culture medium. These mesangial cells also showed recovery of responses to AVP and PDGF by secreting a significantly greater amount of endothelin-1 than the non-stimulated level. These results indicate that heparin potently inhibits mesangial cell endothelin-1 production, especially when stimulated by AVP or PDGF. This inhibitory effect of heparin is probably PKC dependent, and reversible.

Animals↗
PubMed1994

Human gamma-tubulin functions in fission yeast.

gamma-Tubulin is a phylogenetically conserved component of microtubule-organizing centers that is essential for viability and microtubule function. To examine the functional conservation of gamma-tubulin, we have tested the ability of human gamma-tubulin to function in the fission yeast Schizosaccharomyces pombe. We have found that expression of a human gamma-tubulin cDNA restores viability and a near-normal growth rate to cells of S. pombe lacking endogenous gamma-tubulin. Immunofluorescence microscopy showed that these cells contained normal mitotic spindles and interphase microtubule arrays, and that human gamma-tubulin, like S. pombe gamma-tubulin, localized to spindle pole bodies, the fungal microtubule-organizing centers. These results demonstrate that human gamma-tubulin functions in fission yeast, and they suggest that in spite of the great morphological differences between the microtubule-organizing centers of humans and fission yeasts, gamma-tubulin is likely to perform the same tasks in both. They suggest, moreover, that the proteins that interact with gamma-tubulin, including, most obviously, microtubule-organizing center proteins, must also be conserved. We have also found that a fivefold overexpression of S. pombe gamma-tubulin causes no reduction in growth rates or alteration of microtubule organization. We hypothesize that the excess gamma-tubulin is maintained in the cytoplasm in a form incapable of nucleating microtubule assembly. Finally, we have found that expression of human gamma-tubulin or overexpression of S. pombe gamma-tubulin causes no significant alteration of resistance to the antimicrotubule agents benomyl, thiabendazole and nocodazole.

Drug Resistance, Microbial↗
PubMed1994

Cardiac hypertrophy and brain natriuretic peptide in experimental hypertension.

The blood pressure was decreased after chronic treatment with enalapril, MK-954, and hydralazine in deoxycorticosterone acetate (DOCA)-salt-induced malignant hypertension of spontaneously hypertensive rats (SHR); however, ventricular weight and plasma brain natriuretic peptide (BNP) concentration were decreased after enalapril and MK-954 but not after hydralazine. The BNP secretory rates from the ventricle in enalapril- and MK-954-treated DOCA-salt SHR were decreased to approximately 50% of those in untreated DOCA-salt SHR. The BNP secretory rate from the ventricle was positively correlated with ventricular weight in untreated and treated DOCA-salt SHR. In contrast, acute administration of captopril or MK-954 did not decrease the BNP secretory rate from the heart. Results suggest that the decrease in plasma BNP after enalapril and MK-954 is attributed to a decline in the secretion from the ventricle but not from the atrium. The reduction in ventricular mass appeared to be related to this decline.

Animals↗
PubMed1994

Dopamine DA1 receptors on vascular smooth muscle cells are regulated by glucocorticoid and sodium chloride.

The modulation of dopamine DA1 receptors of cultured rat renal arterial smooth muscle cells by glucocorticoid and sodium chloride was studied. At a concentration of 10 nM, the synthetic glucocorticoid dexamethasone increased maximum receptor binding but had no effect on the dissociation constant. However, the maximum binding of [3H]Sch-23390 in cells treated with 100 mM sodium chloride did not change. However, the dissociation constant for DA1 receptor was increased by adding sodium chloride. The glucocorticoid effect on DA1 of arterial smooth muscle cells became apparent after hours of incubation in the presence of the steroid and was significantly inhibited by cycloheximide (10 micrograms/ml) or by the glucocorticoid receptor antagonist RU-38486, indicating that the effect required protein synthesis through glucocorticoid receptors. Treatment of cells with 1 microM dexamethasone for 24 h increased basal and DA1-stimulated adenylate cyclase activity. Basal adenylate cyclase was decreased by sodium chloride in a dose-dependent manner. These results suggest differential control of DA1 receptors on vascular smooth muscle cells by glucocorticoid or sodium chloride.

Adenylyl Cyclases↗
PubMed1994

Phosphoinositide turnover signaling stimulated by ET-3 in endothelial cells from spontaneously hypertensive rats.

Endothelin (ET) B-type receptor-mediated signal transduction after stimulation with ET-3 was examined in cultured aortic endothelial cells obtained from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. The purpose of this study was to elucidate ETB receptor-mediated response in endothelial cells from hypertensive rat models. Non-isopeptide-selective displacement and affinity in these binding experiments suggest that aortic endothelial cell receptors for ET-3 correspond to ETB receptor subtypes. These receptors for ET-3 were similar in WKY and SHR endothelial cells. ETB receptor mRNA expression in cultured endothelial cells was also similar in WKY and SHR. However, the cytosolic free Ca2+ level in the absence of extracellular Ca2+ as well as the inositol 1,4,5-trisphosphate level in response to ET-3 were greater in endothelial cells from SHR than in those from WKY. Phospholipase C and protein kinase C activities after stimulation with ET-3 were also greater in SHR than in WKY. The 6-ketoprostaglandin F1 alpha production was also augmented in SHR, although nitric oxide formation and guanosine 3',5'-cyclic monophosphate production after stimulation with ET-3 were similar in WKY and SHR. We conclude that the phosphoinositide turnover signaling stimulated by ET-3 is augmented in cultured aortic endothelial cells from SHR compared with those from WKY.

Animals↗
PubMed1994

Endothelin modulates the mitogenic effect of PDGF on glomerular mesangial cells.

We showed that two isoforms of platelet-derived growth factor (PDGF), AB and BB, stimulate the secretion of endothelin (ET)-1 from cultured rat mesangial cells. Then, we examined whether PDGF AB and BB stimulate mesangial cell proliferation through the modulation of the endogenous production of ET-1 in these cells. Mitogenesis experiments were assessed by tritiated thymidine incorporation into DNA under highest concentrations (10 ng/ml) of PDGF AB and BB in the presence and absence of anti-ET-1 antiserum or a selective A-type endothelin receptor (ETA receptor) antagonist, BQ-123. PDGF AB and BB potently stimulate thymidine incorporation. This stimulation was significantly attenuated in the presence of either anti-ET-1 antiserum or BQ-123 (10(-7)-10(-5)M). Results suggest that PDGF AB and BB stimulate ET-1 secretion in rat mesangial cells through PDGF beta-receptors, and endogenously produced ET-1 serves to modulate the mitogenic effect of PDGF AB and BB, probably via ETA receptors in these cells.

Animals↗
PubMed1994

Clinical and experimental photosensitivity reaction to tilisolol hydrochloride.

This report describes a patient who developed a photosensitivity reaction during the treatment of hypertension with tilisolol hydrochloride, which is a beta-blocker agent Although the data are insufficient to distinguish photoallergy and phototoxicity, clinical and histologic features suggested that the mechanism involved was photoallergic in nature. The action spectrum was mainly the ultraviolet A range. The reaction was reproducible on oral readministration of the drug and exposure to a low dose of UVA. Photopatch testing with the drug was also positive only in the patient. Although the experimental photoallergic reaction was not induced in the guinea pig, phototoxic potential was demonstrated in the animal. To our knowledge, a photosensitivity reaction due to tilisolol hydrochloride has not been previously reported in the English literature.

Adrenergic beta-Antagonists↗
PubMed1994

Relationship between the regression of left ventricular hypertrophy and the changes in circadian blood pressure after long-term treatment with enalapril in hypertensive patients.

The ambulatory blood pressure (BP) was recorded for 24 hours in 28 untreated hypertensive patients, and mean values of systolic (SBP) and diastolic BP (DBP) were measured over 24 hours, during the day-time (6:00 to 19:30), and during the night-time (20:00 to 5:30). M-mode echocardiography was performed and several parameters of left ventricular size were calculated. In addition, 13 men of 18 patients with left ventricular hypertrophy (LVH) received long-term treatment with enalapril, and ambulatory BP monitoring and echocardiographic measurement were performed in 10 of these patients 6 months after active treatment ended. In all 28 patients, left ventricular mass index (LVMI) was significantly related to 24-hour, day-time and night-time SBP. Other parameters of hypertrophy were correlated with 24-hour and/or night-time BP, but not with day-time BP. In patients with LVH, night-time DBP was significantly higher and the night-time decline in DBP was significantly less than in those without LVH. The 6-month treatment with enalapril clearly decreased casual and ambulatory BP and reduced LVMI. The reduction of LVMI was strongly correlated with the decrease in night-time SBP and DBP compared with the decrease in day-time BP. These observations indicate that LVH is related to 24-hour BP (especially night-time BP) and that the regression of this condition may be related to a decline in night-time BP.

Adult↗
PubMed1993

Serial changes in atrial and brain natriuretic peptides in patients with acute myocardial infarction treated with early coronary angioplasty.

To examine the role of brain natriuretic peptide (BNP) in acute myocardial infarction (AMI), we measured the plasma concentration of immunoreactive (ir) BNP together with that of atrial natriuretic peptide (ANP) over the 4-week course of AMI in 16 patients treated with early coronary angioplasty. Both the plasma ir-ANP and ir-BNP levels were increased on the first day of the infarction compared with the values in normal subjects. During the clinical course of the infarction, the plasma ir-ANP concentration soon decreased, while the plasma ir-BNP level remained elevated at 2 weeks after the infarction, also exhibiting a high level at 4 weeks. Plasma ir-BNP levels on day 1 or days 14 and 28 were inversely correlated with left ventricular ejection fraction obtained by left ventriculography at the acute or chronic phase, respectively. Plasma ir-BNP concentrations on days 14 and 28 were positively correlated with the maximal myosin light chain I level, an indicator of infarct size. These observations suggest that the plasma ir-BNP level increased to compensate for the ventricular dysfunction associated with the size of the infarct in AMI. BNP may act as a cardiac hormone in AMI, differing somewhat from ANP in its synthetic, secretory, or clearance behavior.

Angioplasty, Balloon, Coronary↗
PubMed1993

Stimulation of endothelin-1 release by low density and very low density lipoproteins in cultured human endothelial cells.

To examine the effects of lipoproteins on the secretion of endothelin-1 from endothelial cells, we measured immunoreactive (ir) endothelin-1 release from cultured human umbilical vein endothelial cells in the presence or absence of various concentrations of native low density lipoprotein (LDL), oxidized LDL, and very low density lipoprotein (VLDL). Cultured endothelial cells secreted ir-endothelin-1 into serum-free medium in a time-dependent manner, and the secretion was clearly stimulated following a 15-24-h incubation with 10 micrograms/ml oxidized LDL. The secretion of ir-endothelin-1 increased in a dose-dependent manner after a 24-h incubation with oxidized LDL, while only a high dose of native LDL and VLDL significantly increased ir-endothelin-1 secretion. The release of ir-endothelin-1 stimulated by 20 micrograms/ml oxidized LDL was reproduced by the same concentration of acetylated LDL but not native LDL. These observations indicate that the release of ir-endothelin-1 from endothelial cells is stimulated by lipoproteins, in particular by oxidized LDL, probably through the endothelial scavenger receptor. This increase in ir-endothelin-1 release induced by oxidized LDL may contribute to the development of atherosclerotic vascular lesions.

Cells, Cultured↗
PubMed1993

Effect of endothelin receptor antagonist, BQ-123, on Ca2+ signaling in cultured rat mesangial cells.

Endothelin (ET)-1 causes mesangial cell contraction and proliferation. The present study was designed to evaluate the functional ET receptor subtype in cultured rat mesangial cells by measuring intracellular Ca2+ signaling with the use of a newly synthesized ET receptor type A selective antagonist-BQ123. The ET-1, ET-2 and ET-3 increased intracellular Ca2+ level in a dose-dependent manner. BQ-123 suppressed intracellular Ca2+ elevation in response to ET-1 in a dose-dependent manner with its half maximal inhibition value of 28 nM. BQ-123 (10(-6) M) did not affect ET-3 (10(-7) M)-induced Ca2+ response. The peak Ca2+ levels after addition of ET-3 without BQ-123 were similar to those in response to ET-1, ET-2 and ET-3 in the presence of BQ-123. Northern blot analysis showed that cultured mesangial cells expressed both ETA and ETB receptor mRNA. These results suggest that cultured mesangial cells have, at least, two types of functional receptors, one of which is an ETA receptor.

Amino Acid Sequence↗