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Biomedical subjects

S Miyabo

Publications and source records attributed to S Miyabo.

At least 19 recordsLinked to original sources
PubMed1992

Glucocorticoids increase Ca2+ influx through dihydropyridine-sensitive channels linked to activation of protein kinase C in vascular smooth muscle cells.

To clarify whether protein kinase is associated with glucocorticoid-induced Ca2+ influx into vascular smooth muscle cells, we investigated the effects of protein kinase inhibitors on dexamethasone-induced 45Ca2+ uptake and dihydropyridine binding in A7r5 cells. Protein kinase C inhibitors (staurosporine and UCN-01) abolished the dexamethasone-induced 45Ca2+ uptake and [methyl-3H]PN 200-110 binding. In contrast, KT5720 and KT5823, which are more specific inhibitors of cAMP-dependent protein kinase and cGMP-dependent protein kinase, respectively, did not affect the effects of dexamethasone. Treatment with 100 nM dexamethasone for 48 hours increased protein kinase C activity in A7r5 cells. These results suggest that glucocorticoids increase Ca2+ influx through dihydropyridine-sensitive channels, linked to activation of protein kinase C in vascular smooth muscle cells.

Alkaloids↗
PubMed1992

Corticotroph cell hyperplasia in a patient with Addison disease: case report.

A woman with Addison disease developed hyperpigmentation, headache, and nausea despite conventional replacement therapy with cortisone. Excessively elevated plasma adrenocorticotropic hormone (ACTH) with absence of response to administration of corticotropin-releasing factor (CRF), and roentgenological evidence of enlargement of the sella turcica, as well as detection of enlarged pituitary gland on magnetic resonance images, led to a diagnosis of ACTH-producing microadenoma, which was removed by transsphenoidal microsurgery. The specimen obtained at surgery evidenced corticotroph hyperplasia, as demonstrated by immunohistochemical staining for ACTH. Fine structure exhibited densely granulated cells with a few bundles of microfilaments and an abundance of large lysosomal bodies. Surgical removal of the hyperplasia alleviated the patient's symptoms, and hyperpigmentation faded remarkably. Her plasma ACTH level returned to normal, has remained normal for more than 3 years, and responds adequately to CRF administration.

Addison Disease↗
PubMed1992

Effects of probucol on impaired cardiac performance and lipid metabolism in streptozotocin-induced diabetic rats.

Plasma lipids and cardiac performance were studied in diabetic rats treated with probucol. Male Wistar rats were rendered diabetic with a single intraperitoneal injection of streptozotocin (STZ, 75 mg/kg). Nondiabetic control rats received the vehicle alone. Two weeks after STZ or vehicle injection, control and diabetic rats were randomly assigned to probucol-treated or untreated groups. The rats in the two probucol-treated groups (control- and diabetic-probucol groups) were fed a diet containing 1% probucol (w/w) for 4 weeks. Blood was drawn, and then cardiac performance was assessed by the isolated perfused working heart technique. Probucol treatment had no effect on the cardiac performance of the nondiabetic control rats. The peak left ventricular developed pressure and maximum rate of change in left ventricular pressure during systole were significantly greater in the probucol-treated diabetic rats than in the untreated diabetic rats (p less than 0.05), although cardiac performance did not improve to the level in the nondiabetic rats. Plasma cholesterol, free fatty acid, and phospholipid were significantly elevated in the untreated diabetic rats, and probucol treatment decreased significantly the plasma cholesterol and free fatty acid concentrations (p less than 0.05). These data suggest that probucol treatment improves plasma lipids and cardiac performance in rats with experimental diabetes and may prevent diabetic cardiomyopathy.

Animals↗
PubMed1992

Effect of cilostazol, a cyclic AMP phosphodiesterase inhibitor, on the proliferation of rat aortic smooth muscle cells in culture.

Cilostazol, a cyclic AMP phosphodiesterase inhibitor, has been used as an antiplatelet agent. In the present study, we investigated the in vitro effect of cilostazol on DNA synthesis in rat aortic arterial smooth muscle cells (SMCs) in culture stimulated with fetal calf serum (FCS), platelet-derived growth factor (PDGF), insulin, or insulin-like growth factor-I (IGF-I). Micromolar concentrations of cilostazol inhibited [3H]thymidine incorporation into DNA and cell growth as determined by cell number and protein concentration. Treatment with cilostazol increased the intracellular concentration of cyclic AMP, suggesting that the inhibition of SMC proliferation by cilostazol may be mediated through increased levels of cyclic AMP. The results suggested that cilostazol, by interfering with the proliferation of arterial SMCs, may have potential to prevent initiation and progression of atherosclerosis.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Radioimmunoassay for the determination of 2-methoxyestriol concentration in plasma of pregnant women.

A specific assay method has been developed for the determination of 2-methoxyestriol in plasma of pregnant women. The quantitation was achieved by radioimmunoassay after extraction of the plasma with ethyl acetate and purification on a Sephadex LH-20 column. In order to obtain the immunogen for 2-methoxyestriol, 6-oxo-2-methoxyestriol was converted to its 6-(O-carboxymethyl)oxime derivative. The derivative was then coupled to bovine serum albumin by the mixed anhydride method, and rabbits were immunized with this conjugate. The antiserum obtained was partially purified by affinity chromatography on estrone 17-(O-carboxymethyl)oxime-aminohexyl Sepharose conjugate to eliminate the cross-reactive antibodies. Plasma 2-methoxyestriol concentrations in pregnancy were estimated to be mean values of 41.1 pg/ml (12th-14th week), 85.3 pg/ml (27th-29th week), and 97.5 pg/ml (37th-41st week).

Cross Reactions↗
PubMed1992

[Theophylline toxicity in a patient with status asthmaticus].

A 70-year-old woman was hospitalized for status asthmaticus. The level of CRP was high and chest roentgenogram showed infiltrative shadows in the left middle lung field. Artificial respiration and continuous infusion of methylprednisolone and aminophylline 750 mg/24 hr were performed. Eight hours after admission, seizures suddenly occurred. At this time, brain CT showed no abnormal findings. The seizures were thought to be induced by theophylline toxicity, since serum theophylline concentration was high at 69.9 micrograms/ml. Because theophylline clearance of the patient in a clinically stable condition was normal, it was speculated that theophylline clearance was reduced during status asthmaticus. It is thought that this rare case of theophylline toxicity occurred due to reduction of theophylline clearance during status asthmaticus associated with pneumonia.

Aged↗
PubMed1992

[Bronchial hyperresponsiveness to acetylcholine during acute pulmonary congestion in guinea pigs].

To understand the precise mechanism of bronchial hyperresponsiveness in patients with congestive heart failure, we studied the effect of mild pulmonary congestion on bronchial responsiveness to inhaled acetylcholine (ACh) in guinea pigs. We induced mild pulmonary congestion by inflation of a balloon placed in the left atrium, and maintained the left atrial pressure (Pla) at 10 mmHg for 30 minutes with continuous monitoring of lung resistance (RL) and dynamic compliance (Cdyn). Furthermore, we determined the provocative concentration of ACh producing 100% increase in RL (PC100-ACh), before and during balloon inflation. In animals with propranolol pretreatment, but not in animals without propranolol pretreatment, mild pulmonary congestion caused slight increase in RL (N.S.) and significant decrease in Cdyn (p less than 0.01) and PC 100-ACh (p less than 0.01). Cutting of bilateral vagal nerves partially inhibited the decrease of PC100-ACh, but pretreatment with either phenoxybenzamine, indomethacin, AA-861 or OKY-046 had not effect. These results suggest that blockade of beta-adrenergic receptors and the vagal reflex, but not of alpha-adrenergic receptors or arachidonates, contributes to bronchial hyperresponsiveness during acute pulmonary congestion.

Acetylcholine↗
PubMed1992

[Probucol inhibits tobacco smoke-induced decrease in plasma anti-elastase activity and ferroxidase activity in rats].

Elastolytic enzymes and active oxygen species derived from leukocytes and alveolar macrophages during exposure to tobacco smoke, together with active oxygen species directly derived from tobacco smoke, are thought to play a crucial role in the pathogenesis of pulmonary emphysema by inactivating alpha 1 protease inhibitor (alpha 1 PI), a novel anti-elastase. We studied the inhibitory effect of probucol, an oral hypocholesterolemic agent, on tobacco smoke-induced decrease in plasma anti-elastase activity (EIA) and ferroxidase activity (FA) in conscious venous catheter instrumented rats. Rats exposed to the smoke of 5 cigarettes (nicotine 11 mg, tar 115 mg) in a plastic chamber showed a prompt increase in plasma COHb to 17.9 +/- 2.7%, and a prompt decrease in plasma EIA by -17.9% (p less than 0.05) and FA by -14.8% (p less than 0.01), which lasted for 6 hours after exposure. Rats administered probucol (1% probucol in food) for 3 days showed normal cholesterol plasma levels, and rats administered probucol for 4 weeks showed hypocholesterolemic plasma levels. EIA and FA were not depressed after smoking, and lipid peroxide product (TBA reactive substance) in lung tissue (p less than 0.05) and serum (p less than 0.1) showed a smaller increase in association with a smaller decrease in the ratio of lung tissue GSH/GSSG (p less than 0.01) compared with control rats. These results indicate that probucol, via its antioxidant action rather than its cholesterol lowering effect, has a protective effect on lung exposed to tobacco smoke in terms of protease-antiprotease balance and oxidant-antioxidant balance.

Animals↗
PubMed1992

[Effects of inhaled and intravenous furosemide on bronchial hyperresponsiveness in patients with chronic congestive heart failure].

We studied the effects of inhaled and intravenous furosemide (40 mg) on bronchial responsiveness to acetylcholine (ACh) in patients with chronic congestive heart failure. The measurement of bronchial responsiveness was performed by inhaling doses of ACh and calculating the provocative concentration of ACh needed to cause a 20% fall in FEV1.0 (PC20-ACh). Intravenous furosemide (N = 11) had a marked diuretic effect (urine output 1014 ml (SEM 156) in 2 hours), but had no effect on resting pulmonary function and PC20-ACh. In contrast, inhaled furosemide (N = 10) had no effect on urine output and resting pulmonary function, but caused significant increase in PC20-ACh from 2.74 (GSEM 1.28) to 8.47 (GSEM 1.22) mg/ml (p less than 0.05). We conclude that inhaled furosemide, but not intravenous furosemide reduces bronchial hyperresponsiveness to ACh in patients with chronic congestive heart failure. The mechanism of this effect appears to be related to the ion transport system of airway epithelium.

Administration, Inhalation↗
PubMed1992

Apolipoprotein(a) is present in urine and its excretion is decreased in patients with renal failure.

To investigate the relation between renal function and concentrations of lipoprotein(a) [Lp(a)] in serum, we measured Lp(a) in samples of serum and urine from patients with diabetes mellitus and in samples sent to a laboratory center for measurements of creatinine clearance. Serum Lp(a) concentrations were significantly increased in subjects with obvious renal dysfunction (serum creatinine > or = 176.8 mumol/L) compared with normal control subjects. Urinary Lp(a) excretion was decreased in subjects with obvious renal dysfunction compared with subjects without obvious renal dysfunction (serum creatinine < or = 88.4 mumol/L) and was negatively and positively correlated with serum creatinine and creatinine clearance, respectively. More than 80% of urinary Lp(a) was recovered in the d > 1.21 kg/L fraction. At least six bands for apolipoprotein(a) [apo(a)] fragments, which were smaller than native apo(a) in serum, were observed in urine by immunoblotting, and some of these were also detected in serum. Degraded apo(a) fragments are probably present in urine, and their excretion decreases in parallel with decreases in the glomerular filtration rate.

Adult↗
PubMed1992

[A case of pulmonary tuberculosis associated with severe respiratory failure, DIC and intractable bilateral pneumothoraces].

We had a sixty-five year old male patient who suddenly complained of dyspnea and fever with pulmonary tuberculosis, severe respiratory failure, disseminated intravascular coagulation (DIC) and intractable bilateral pneumothoraces. From the first hospital day severe hypoxemia which did not respond to conventional oxygen therapy developed with a diffuse ill-defined reticulo-nodular shadow in the plain chest x-ray film. On the 2nd hospital day mechanical ventilation with 2cmH2O PEEP was introduced. Antituberculous agents as well as corticosteroids were started suspecting acute interstitial pneumonia with pulmonary tuberculosis and adult respiratory distress syndrome (ARDS). Medication was followed by the treatment of Gabexate mesilate and heparin against DIC on laboratory data. Though clinical findings and pulmonary infiltrate on chest x-ray film transiently improved, right pneumothorax occurred suddenly on the 6th day followed with left pneumothorax on the 36th day. Tube drainage of both pleural spaces and repeated instillation of thrombin-rich oxycel cotton via bronchofiberscope failed to stop air leakage. He ultimately expired on 49th hospital day. At postmortem lung had multiple bilateral bulla several of which ruptured to the pleural site and caseating necrotic area containing bacilli positively stained with Ziehl-Nielsen stain in the bilateral upper lobe. No typical caseating necrotic lesion, however, was found in the other lung tissue. Therefore, it seemed to show a chronic phase of diffuse alveolar damage (DAD).

Aged↗
PubMed1992

31P-nuclear magnetic resonance evidence of abnormal skeletal muscle metabolism in patients with chronic lung disease and congestive heart failure.

The development of 31P-nuclear magnetic resonance (NMR) has enabled direct and non-invasive measurements of muscle metabolism. Serial measurements of the phosphocreatine/inorganic phosphate (PCr/Pi) ratio, which is closely related to the adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio and pH during and after forearm exercise were performed in 11 patients with chronic lung disease (CLD), nine patients with chronic heart failure (CHF) and eight control subjects. As compared with control subjects, the PCr/Pi ratio in the patients with CLD or CHF was lower during the recovery period and significantly lower at three and 4 min exercise. The pH values after exercise were lower in patients with CLD or CHF compared to control subjects. The PCr/Pi ratio at 4 min after exercise in the patients with CLD or CHF did not correlate with parameters of cardiac function or arterial and mixed venous oxygen tension. The arterial oxygen content and output in patients with CLD and CHF were significantly lower than that of control subjects. Nutritional parameters were not statistically different among the three groups. These observations suggest that metabolic abnormalities may be present in the skeletal muscles of patients with CLD and CHF that are not due to under-nutrition. These may result from reduced arterial oxygen output and, partially, from physical detraining.

Aged↗
PubMed1992

[Leukotoxin, 9,10-epoxy-12-octadecenoate, causes vasodilation in isolated pulmonary artery rings preconstricted with endothelin 1].

Leukotoxin, a cytochrome P450-dependent metabolite of linoleate synthesized by neutrophils, caused dose dependent vasodilation (10(15)-5 x 10(-4) M) of isolated rat pulmonary arterial rings preconstricted with endothelin 1 (10(-8) M), although similar doses of linoleate had no effect. The relaxing effect of leukotoxin was largely ablated by mechanical denudation of the endothelium and by treatment with L-NMMA (1 mM) and methylene blue (5 x 10(-6) M), but not indomethacin (10(-5) M). Endothelium-independent relaxation of leukotoxin was not inhibited by pretreatment with nicardipine (10(-6) M) in both pulmonary arterial rings and aortic rings. In A7r5 cultured rat aortic smooth muscle cells, leukotoxin markedly inhibited Ca2+ uptake in the basal nonstimulated state, and in the stimulated state with endothelin 1. We conclude that leukotoxin causes vascular tone-dependent vasodilation via augmentation of EDRF production, and causes decrease of intracellular calcium concentration that is not related to the dihydropyridine-sensitive calcium channel, which may be a mechanism of the endothelium-independent relaxation caused by leukotoxin.

Animals↗
PubMed1992

[Inhibitory effects of alpha 1 protease inhibitor on the production of IL-1 and TNF alpha by alveolar macrophages in patients with lung cancer].

In the present study, we investigated the effect of alpha 1 protease inhibitor (alpha 1PI) on the production of interleukin-1 alpha (IL-1 alpha, ELISA), IL-1 beta (ELISA), and tumor necrosis factor alpha (TNF alpha, ELISA) by alveolar macrophages (AM) recruited by bronchoalveolar lavage (BAL) from patients with lung cancer and benign pulmonary diseases. Levels of BALF alpha 1PI were significantly increased in patients with lung cancer compared with benign pulmonary diseases. When BALF AM were cultured and stimulated by LPS (20 micrograms/ml) for 48 hours, production of IL-1 alpha and IL-1 beta was less marked in patients with lung production showed a similar tendency, but the difference between patients with lung cancer and benign pulmonary diseases was not significant. Addition of alpha 1PI to the LPS-stimulated AM culture system inhibited production of these cytokines dose-dependently. Thus, the local increase of alpha 1PI in lung cancer may act as a humoral inhibitor against the production of IL-1 and TNF by AM.

Adult↗
PubMed1991

[Endothelin 3 (ET3) stimulates the hypothalamic-pituitary-adrenal axis mainly by corticotropin-releasing-hormone (CRH)].

Endothelin 3 (ET3) is a member of the novel vasoconstrictive peptide family, identified in the porcine central nervous system. The effect of ET3 on the hypothalamic-pituitary-adrenal axis in male rats was examined in vivo and in vitro. Intravenous bolus injection of 1000pmol/kg of ET3 in free moving rats caused significant increases in plasma ACTH and corticosterone levels, almost equivalent to those of 100pmol/kg of rat corticotropin-releasing hormone (rCRH). Since an iv bolus injection of ET3 1000pmol/kg did not cause significant changes in the blood pressure of anesthetized rats or the locomotor activity of free moving rats, it seems unlikely that ET3 1000pmol/kg acted as a nonspecific stressor. When ET3 (10(-11) greater than 10(-7)M) was added to cultured anterior pituitary cells, neither direct stimulation of ACTH release nor potentiation of rCRH action was noted. Although it has been shown that ET3 administered systemically probably does not cross the brain-blood-barrier, circulating ET3 may reach the brain tissues through regions lacking the tight barrier, circumventricular structures. The next studies included pretreatment of antagonists or blockers of ACTH stimulating hormones to elucidate the mechanisms of ET3 induced ACTH release. The action of ET3 was virtually abolished by pretreatment of CRH-antagonist alpha helical CRH (150 micrograms/rat icv). But pretreatment of catecholamine-blocker alpha methyl-tyrosine (100mg/kg iv), arginine vasopressin-antagonist dP-thy(Me)AVP (50 micrograms/rat iv) and prostaglandin-blocker indomethacin (3mg/rat iv) did not inhibit the action of ET3. The results indicate that ET3 may play the role of a neuropeptide and that the stimulation of the CRH-neurons is mainly responsible for activation of ACTH and corticosterone release.

Adrenocorticotropic Hormone↗
PubMed1991

The lectin wheat germ agglutinin induces rapid protein-tyrosine phosphorylation in human platelets.

In response to wheat germ agglutinin (WGA), platelet aggregation and stimulation of protein-tyrosine phosphorylation were observed in a dose dependent manner. These reactions were completely inhibited by coexistence of N-acetyl-D-glucosamine with WGA. Upon stimulation by this agonist, protein-tyrosine phosphorylation of seven bands with molecular masses of 140-, 130-, 80-, 76-, 53-, 38- and 35-kDa proteins was observed by immunoblot. These protein-tyrosine phosphorylations were divided into three groups by kinetics. Considering the previous report from our laboratory that thrombin and collagen induced tyrosine phosphorylation in 135-, 124- and 76-kDa proteins (Nakamura, S. and Yamamura, H. (1989) J. Biol. Chem. 264, 7089-7091.), there may be another signal transduction pathway in tyrosine phosphorylation of human platelets.

Blood Platelets↗
PubMed1991

Endothelin-3 stimulates the hypothalamic-pituitary-adrenal axis.

Endothelin-3 (ET-3) is a member of the novel vasoconstrictive peptide family, identified in porcine central nervous system. Intravenous bolus injection of 1000 pmol/kg of ET-3 in freely moving rats caused significant increases in plasma ACTH and corticosterone levels, almost equivalent to those of 100 pmol/kg of rat corticotropin-releasing hormone (rCRH). The action of ET-3 was virtually abolished by pretreatment of CRH-antagonist, alpha-helical CRH. When ET-3 was added to cultured anterior pituitary cells, neither direct stimulation of ACTH release nor potentiation of rCRH action was noted. The results indicate that ET-3 may function as a neuropeptide and stimulation of the CRH-neurons, direct or inderect, is mainly responsible for activation of ACTH and corticosterone release.

Adrenal Glands↗