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Biomedical subjects

T Satake

Publications and source records attributed to T Satake.

At least 163 records · Page 9Linked to original sources
PubMed1986

Plasma-free eicosapentaenoic acid/arachidonic acid ratio: a possible new coronary risk factor.

Seventy-six effort angina patients who had typical angina on exertion documented by treadmill stress test with evidence of ischemic ST-segment depression and 78 healthy volunteers in urban Japan were investigated in this study. Plasma free fatty acids (FFA) in both groups were determined using high-performance liquid chromatography. The relationships between the total cholesterol, high-density lipoprotein (HDL), triglycerides in plasma, and the genesis of coronary heart disease were also examined. The ratio (0.08 +/- 0.08) of eicosapentaenoic acid (EPA)/arachidonic acid (AA) in plasma FFA was significantly lower in effort angina patients than that (0.15 +/- 0.12) in healthy volunteers. The lower ratio was due to significantly lower levels of EPA in the patients than in normals. In 42% of angina patients, the ratio is below 0.03. In all age subgroups except the age 30-39 subgroup, the ratio of EPA/AA was significantly lower in patients than in normals, when divided into four subgroups by using a 10-year age interval. Though the total cholesterol and triglycerides were not significantly different between the two groups, HDL was significantly lower and total cholesterol/HDL ratio was significantly higher in effort angina patients than in healthy volunteers. However, there was no correlation between EPA/AA ratio and HDL in individuals in either group. From these results, it could be concluded that lower EPA/AA ratio is a new coronary risk indicator other than HDL.

Adult↗
PubMed1986

Clinical evaluation of serum 3 beta-hydroxy-5-cholenoic acid in hepatobiliary diseases.

Serum 3 beta-hydroxy-5-cholenoic acid (3 beta-OH-delta 5) was analyzed in 100 cases (90 patients with hepatobiliary diseases, 10 normal subjects) and its clinical significance investigated. The measurement of 3 beta-OH-delta 5 was performed by high performance liquid chromatography (HPLC) with immobilized 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) as the enzyme column. Esterified 3 beta-OH-delta 5 was measured after enzymatic hydrolysis with sulfatase and beta-glucuronidase. 3 beta-OH-delta 5 was hardly detected in normal cases. On the other hand, serum 3 beta-OH-delta 5 levels were remarkably high in cholestatic cases and also high in other cases with high bilirubin levels. The ratio of glycine- to taurine-conjugates (G/T ratio) was effective in discriminating cholestasis from hepatocellular damage such as in cases of acute hepatitis or fulminant hepatitis. More than 90% of the 3 beta-OH-delta 5, which is toxic, was sulfated or glucuronidated, suggesting detoxification by esterified bile acids. Significant increases of taurine-conjugated 3 beta-OH-delta 5 were observed in cases with pruritus, and a relationship between taurine-conjugated and pruritus was presumed. Therefore, analysis of 3 beta-OH-delta 5 is considered to be effective in clarifying the pathogenesis of hepatobiliary diseases.

3-Hydroxysteroid Dehydrogenases↗
PubMed1986

Increased cyclic GMP in atrial fibrillation.

To investigate the role of cyclic nucleotides in the genesis and/or the persistence of atrial fibrillation (AF), plasma levels of cyclic GMP (c-GMP) and cyclic AMP (c-AMP) were measured in dogs with electrically induced AF, and in dogs subjected to high frequency (230 or 410/min) atrial pacing. The atrial fibrillation threshold (AFT) after intravenous administration of a dibutyryl derivative of c-GMP (Dbc-GMP), and the effect of atropine (0.1 mg/kg) on AFT were determined. Plasma levels of c-GMP and c-AMP were also measured in patients during paroxysmal AF and sinus rhythm. The c-GMP level increased significantly 15 min after the onset of artificial AF, and gradually increased during the course of the experiment. The c-GMP level began to increase significantly 15 min after the initiation of pacing at the higher rate (410/min) but not at the lower rate, compared to the prepacing value. The c-GMP level continued to rise until the end of pacing in the animals paced at 410/min. Although Dbc-GMP induced a dose-dependent decrease in AFT, atropine did not prevent the decrease in AFT by Dbc-GMP. In contrast, c-AMP levels were not significantly affected in any of these experiments. Clinical assessment revealed that patients had almost four times higher c-GMP level during AF than during sinus rhythm, though c-AMP levels in these patients did not change significantly during the attack of AF. These results suggest that the increase in c-GMP plays an important role in the maintenance and/or the genesis of AF.

Animals↗
PubMed1986

The role of phospholipase in the genesis of reperfusion arrhythmia.

To clarify the mechanism of reperfusion arrhythmia, the following experiments were performed. In vivo study: Using anesthetized mongrel dogs, the left anterior descending coronary artery was occluded for 15 min and the ligation was released. The dogs were divided into two groups depending on whether the pretreatment was with saline or coenzyme Q10 (CoQ10), 15 mg/kg, before the ligation, i.e., the control and the CoQ10 groups. Each group was further divided into two subgroups depending on the presence or the absence of reperfusion arrhythmia. Reperfusion arrhythmia was observed in 12 out of 38 dogs in the control, whereas in the CoQ10 group none developed arrhythmia. Nine species of free fatty acids (FFA) were detected in the plasma membrane in each group. In the dogs in the control group with arrhythmia, all species of detected FFA increased, and phospholipid content in plasma membrane decreased. These changes were not observed in the dogs without arrhythmia in both the control and the CoQ10 groups. In vitro study: Incubation of myocardial plasma membrane with phospholipase (PLase) A2 increased only unsaturated FFA, while PLase C increased all detected FFA. Premedication with CoQ10 prevented the increase in FFA caused by PLases. Perfusion with PLase A2 or C altered membrane action potential. Premedication with CoQ10 also prevented changes in membrane action potential. PLase liberates fatty acids from phospholipids, and CoQ10 is known to protect the membrane phospholipids from the attack of PLase. These facts and results suggest that activation of PLase associated with coronary reperfusion is closely related to the development of reperfusion arrhythmia.

Animals↗
PubMed1986

Mechanism of cardiac arrhythmias induced by epinephrine in dogs with hypokalemia.

To investigate the mechanism of ventricular arrhythmias induced by epinephrine in dogs with hypokalemia, 30 adult mongrel dogs were separated into a control group (n = 13) and a hypokalemia group (n = 17). In the hypokalemia group, sodium polystyrene sulfonate (5 g/kg body weight) was infused into the colon. In both groups, the serum concentrations of sodium, potassium and calcium were measured every 15 minutes for 60 minutes. The mean (+/- standard deviation) serum potassium level of the hypokalemia group decreased significantly from 3.81 +/- 0.21 to 2.92 +/- 0.36 mEq/liter; there were no significant changes in other electrolytes. After 60 minutes, epinephrine (10 micrograms/kg) was injected intravenously in the hypokalemia and control groups, and the arrhythmia ratio (the number of ventricular ectopic beats divided by the total heart rate) was calculated for 5 minutes. Each group was further classified into subgroups of dogs with an arrhythmia ratio higher or lower than 10%. An arrhythmia ratio over 10% was observed in 7.7% of the control group and 53% of the hypokalemia group. Immediately after 5 minutes of epinephrine injection, myocardial mitochondria and plasma membrane fraction were prepared from each group. Mitochondrial calcium content and phospholipase activity of plasma membrane fraction were determined. Significant increases in both mitochondrial calcium content and phospholipase activity were observed in the dogs with hypokalemia and an arrhythmia ratio greater than 10%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

The relationship between tissue levels of cyclic GMP and tracheal smooth muscle relaxation in the guinea-pig.

The effect of cyclic GMP was investigated using guinea-pig tracheal smooth muscle. 8-Bromo-cyclic GMP showed a dose-dependent relaxation of spontaneous tension of tracheal smooth muscle. Administration of sodium nitroprusside induced dose-dependent relaxation of tracheal smooth muscle as well as an increase in tissue levels of cyclic GMP. Nicorandil, N-(2-hydroxyethyl) nicotinamide nitrate showed dose-dependent relaxation of tracheal smooth muscle and an increase in cyclic GMP levels in the tissue. N-(2-aminoethyl) nicotinamide dihydrochloride, which is a nicorandil derivative and differs minimally in its molecular structure (-NH2 vs -NO2), had neither a relaxant effect on tracheal smooth muscle nor did it increase the level of cyclic GMP in the tissue. The rise cyclic GMP levels preceded the relaxation of tracheal smooth muscle induced by sodium nitroprusside. These results suggest that cyclic GMP is one of the relaxant factors and that nitro-derivatives exhibit their relaxant effect on the smooth muscle mediated by an increase in cyclic GMP level.

Animals↗
PubMed1986

Neoplastic nature of argyrophil cells in urachal adenocarcinoma.

The histological, histochemical and electron microscopic features of the metastatic tumors of an urachal adenocarcinoma, were presented. Metastatic tumor nodules in the lungs and brain as well as the primary tumor showed tubular adenocarcinoma containing many argyrophil cells. Immunoperoxidase examination revealed three kind of endocrine cells which contained different endocrine hormones. Electron microscopic examination showed small, round endocrine granules in the endocrine cells and desmosome-like complexes in between these cells and the adjacent glandular neoplastic cells. These findings suggested that the endocrine cells were neoplastic in nature and originated from primitive neoplastic cells as well as glandular neoplastic cells.

Adenocarcinoma↗
PubMed1986

Effects of verapamil on the response of the guinea-pig tracheal muscle to carbachol.

The effects of verapamil on the contraction of the guinea-pig tracheal smooth muscle induced by calcium (Ca2+) or barium (Ba2+) were investigated in three different conditions: (a) in excess K solution, (b) in the presence of carbachol, and (c) in excess K solution containing carbachol. In order to clarify the contractions, the effects of removal and readdition of the divalent cations were also investigated. In Ca2+-loaded tissues, application of carbachol in Ca-free medium produced a transient contraction, the magnitude of which decreased the longer the duration of exposure to Ca2+-free solution. In Ca2+-depleted, Ba2+-loaded tissues, application of carbachol in a Ba2+- and Ca2+-free medium produced a transient contraction the magnitude of which decreased the longer the duration of exposure to the Ba2+- and Ca2+-free solution. After exposure to Ca2+-free solution for 40 min, the sensitivity of the tissue to Ca2+ was greater in the presence of 30 microM carbachol (ED50 = 0.06 mM) than in the presence of 40 mM K+ (ED50 = 0.3 mM). The Ca2+-sensitivity in the presence of 30 microM carbachol plus K+ (40 mM) was not different from that in the presence of 30 microM carbachol alone. In Ca2+-free solution, the sensitivity of the tissue to Ba2+ in the presence of 40 mM K+ (ED50 = 1.4 mM) was not different from that observed in the presence of 30 microM carbachol (ED50 = 1.3 mM). 6 After exposure to Ca2+-free solution, verapamil produced a parallel rightward shift in the concentration-response curves to added Ca2+ and Ba2+ in the presence of either 40 mM K+, 30 microM carbachol or 40mM K+ plus 30 microM carbachol. 7 The pA2 values of verapamil against Ca2+ responses in the presence of 40 mM K+, 30 microM carbachol and 40 mM K+ plus 30 microM carbachol were 7.0, 6.5 and 6.5, respectively. The pA2 values of verapamil against Ba2+ responses under these conditions were 7.1, 7.0 and 7.1, respectively. 8 It is concluded that the sustained contraction produced by carbachol requires the influx of Ca2+ and that Ba2+ can substitute for Ca2+ in this process. Furthermore, the ionic channels which admit Ca2+ may be modified by carbachol to different degrees depending on the presence of Ca2+ or Ba2+. Such changes alter the affinity of the channel to verapamil.

Animals↗
PubMed1986

Effects of relaxants on electrical and mechanical activities in the guinea-pig tracheal muscle.

In isolated tracheal muscles of the guinea-pig, effects of several relaxants were studied by simultaneously recording the membrane potential and mechanical response. Intracellular recordings showed regular slow waves in most preparations. There was a close correlation between membrane potential and slow wave amplitude. The linear regression line of the slow wave amplitude (Y mV) on the membrane potential (X mV) could be expressed by Y = -0.35X-5.9. The mean values of resting potential and slow wave amplitude were -50.6 +/- 0.6 mV and 11.9 +/- 0.5 mV, respectively. Relaxant drugs used (isoprenaline, terbutaline, adrenaline, noradrenaline, theophylline, forskolin and dibutyryl cyclic AMP) all produced hyperpolarization of the membrane and abolished the slow wave. The degree of relaxation was closely related to these electrical responses, although the recovery of electrical responses was faster than the mechanical response. It was concluded that the relaxation caused by the agents, which are known to increase the intracellular cyclic AMP level, was accompanied by a clear hyperpolarization and suppression of slow waves.

Animals↗
PubMed1986

The role of phospholipase in reduced beta-adrenergic responsiveness in experimental asthma.

This investigation was designed to elucidate the role of phospholipase (PLase) in relation to reduced beta-adrenergic responsiveness in guinea pigs subjected to experimental asthma. In the in vivo experiment, guinea pigs that had developed asthma-like symptoms after exposure to an aerosol of 2% ovalbumin for 7 to 8 min for 10 successive days were used as the experimental asthma group. The control group was exposed to saline. The endogenous PLase activity was determined by high performance liquid chromatography using ditridecanoyl phosphatidylcholine as a substrate. PLase activity of lung membranes in the experimental asthma group was significantly elevated by 50% compared with that in the control group. Phospholipid content of lung membranes in the experimental asthma group was decreased by 11% compared with that in the control group. The experimental asthma group showed a 37% decrease in the number of beta-adrenoceptors in lung membranes and a 54% decrease in isoproterenol-stimulated adenylate cyclase activity in lung membranes compared with the control group. Although forskolin-stimulated adenylate cyclase activity was also reduced by 24%, decreases in forskolin-stimulated activity were less than decreases in isoproterenol-stimulated activity. In the in vitro experiment phospholipids in lung membranes were degraded by pretreatment with 0.1 U of PLase A2. After pretreatment of lung membranes with PLase A2, the number of beta-adrenoceptors was reduced by 25% compared with that in the control group, and adenylate cyclase activity stimulated by isoproterenol and forskolin were also reduced by 67 and 28%, respectively. PLase A2 had a minor effect on forskolin-stimulated activity as compared with isoproterenol-stimulated activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1986

Role of cyclic GMP of canine vascular smooth muscle in relaxation by organic nitrates.

The effects of organic nitrates on tone and tissue cyclic nucleotide levels were studied, using canine coronary, mesenteric and renal arteries, and femoral veins. Glyceryl trinitrate (GTN) relaxed all vascular tissues examined and increased tissue cyclic GMP (cGMP) levels in a concentration-dependent manner, but GTN induced no significant changes in cyclic AMP (cAMP) levels. An increase in cGMP levels induced by 10 microM of GTN in coronary arteries was observed before the onset of relaxation. Methylene blue, an inhibitor of guanylate cyclase, inhibited the relaxant effect of GTN and decreased cGMP levels. In contrast, M & B 22,948, an inhibitor of cGMP phosphodiesterase, not only enhanced relaxation by GTN, but also increased cGMP levels. Other organic nitrates, pentaerythritol tetranitrate (PETN), nicorandil (NIC), and isosorbide dinitrate (ISDN), also relaxed coronary arteries and increased cGMP levels in a concentration-dependent manner. A significant correlation was observed between percentage increases in cGMP levels and percentage relaxation by 10 microM of GTN, PETN, NIC, and ISDN (r = 0.952, p less than 0.001). Plasma concentrations of 4 organic nitrates inversely correlated with percentage increases in cGMP levels by 10 microM of these agents in coronary arteries (r = -0.845, p less than 0.001). These results suggest that an increase in cGMP is responsible for relaxation in vascular smooth muscles by organic nitrates, and that therapeutic plasma concentrations may be estimated by the degree of increase in cGMP levels induced by their administration.

Animals↗
PubMed1986

Hemodynamic effects of BTB-cyclic AMP in anesthetized dogs.

The hemodynamic effects of 8-benzylthio-N6-n butyl adenosine 3',5' cyclic monophosphate (BTB-cAMP) were studied in anesthetized dogs. BTB-cAMP was given intravenously in doses of 1, 3 and 9 mg/kg, respectively. BTB-cAMP induced dose-dependent increases in heart rate, max LV dp/dt, cardiac output and stroke volume, and decreases in mean blood pressure and total peripheral resistance. BTB-cAMP had less of an effect on heart rate and blood pressure than dibutyryl cAMP (DB-cAMP), but showed a greater effect in augmenting cardiac contractility, with earlier manifestations of maximum action. Although the duration of its action is shorter, BTB-cAMP has possible therapeutic applications in cardiovascular diseases such as cardiogenic shock and congestive heart failure. It may also be a better agent than DB-cAMP for the treatment of patients with congestive heart failure because of a less potent hypotensive effect.

Animals↗
PubMed1986

The role of leukotriene B4 in the genesis of oxygen toxicity in the lung.

Leukotriene B4 (LTB4) is a metabolite of arachidonic acid that has potent chemotactic activity for polymorphonuclear leukocytes (PMN). Pulmonary oxygen toxicity is considered to be a good model of an acute inflammatory lung injury, and an increase in the number of PMN is found in the lungs acutely injured by hyperoxia. In order to estimate the role of LTB4 responsible for this influx of PMN, we measured the LTB4 by radioimmunoassay in lung lavages of rats exposed to hyperoxia for 60 h. We found that the level of LTB4 in lung lavages in rats exposed to hyperoxia for 60 h increased significantly compared with that in normoxic control rats. At the same time, the marked increase in the number of PMN in lung lavages and the decrease in the activity of NADPH-cytochrome c reductase in lung microsomes were also observed. The administration of AA861, a 5-lipoxygenase inhibitor, reduced not only the increase in LTB4 but also the increase in the number of PMN in lung lavages of rats exposed to hyperoxia for 60 h. Furthermore, treatment with AA861 also protected the decrease in the activity of NADPH-cytochrome c reductase. The effects of AA861 on these parameters were observed in a dose-dependent fashion. In addition, there is a good correlation between the level of LTB4 and the number of PMN in the lavage of rats exposed to hyperoxia for 60 h with or without AA861 administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Possible mechanisms of elevation of serum secretory immunoglobulin A in liver diseases.

In order to investigate possible mechanisms of elevation of serum secretory immunoglobulin A (sIgA) in liver diseases, human liver specimens were applied to immunohistochemical study of immunoglobulin A, secretory component, and J chain, which are components of sIgA. In the cases of chronic hepatitis with high serum sIgA levels, these antigens were present in dilated bile canaliculi of hepatocytes and they were continuously stained on the lateral plasma membrane of hepatocytes from the bile canaliculus to the space of Disse over the junctional complexes. Furthermore, in liver cirrhosis and extrahepatic cholestasis, they were also detected in intraportal bile ductules and intercellular spaces of degenerated cholangiocytes. These results suggest that at least two pathways might allow elevation of serum sIgA: through the communication of the bile canaliculus with the space of Disse over junctional complexes and through the bile ductule into the portal blood vessel.

Bile Canaliculi↗