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Biomedical subjects

S Takeo

Publications and source records attributed to S Takeo.

205 records · Page 12Linked to original sources

Irreversible changes in oxidative phosphorylation activity of the mitochondrial membrane from hearts subjected to hypoxia and reoxygenation.

The present study was designed to elucidate irreversible biochemical changes in the mitochondrial membrane of hearts subjected to hypoxia and subsequent reoxygenation in a rabbit heart Langendorff preparation. Significant changes in the mitochondrial calcium uptake, ATPase, and oxidative phosphorylation activities were seen in the heart receiving 30 to 60 min of hypoxic perfusion. These changes were accompanied by deleterious alterations in contractile function. Among hypoxia-induced changes in biochemical activities of isolated mitochondria, only oxidative phosphorylation activity was found to be irreversible upon reoxygenation. This is compatible with the findings of reoxygenation-induced incomplete recovery of tissue ATP level, once decreased by hypoxic perfusion. In the electron microscopic study, the heart receiving 60 min of hypoxic perfusion showed contracted sarcomeres, vacuolization and electron lucency of the mitochondria which were not restored by the subsequent reoxygenation. The results suggest that an inability of the mitochondrial membrane to produce high-energy phosphate primarily induces lack of ATP required for cardiac mechanical activity and membrane integrity, which in turn leads to the impairment of myocardial cell function.

Adenosine Triphosphatases↗

Alterations in sarcolemmal Na+-Ca2+ exchange and ATP-dependent Ca2+-binding in hypertrophied heart.

In order to examine changes in Ca2+ transport in heart sarcolemma, cardiac hypertrophy was induced in rabbits by stenosis of the abdominal aorta and hearts were removed 18-20 weeks later; sham-operated normal rabbits were used as controls. Sarcolemmal vesicles were isolated from the left ventricular tissue by a sucrose density gradient method and the membrane composition as well as activities of certain marker enzymes were monitored to determine the purity of control and experimental fractions; Na+-Ca2+ exchange and Ca2+-pump activities were assessed by the Millipore filtration technique. No changes in Ca2+-influx were observed in Na+-loaded vesicles from the hypertrophied hearts when studied in the presence of different concentrations of calcium as well as at different times of incubation. In contrast, Na+-induced Ca2+-efflux from Ca2+-loaded vesicles was enhanced in the hypertrophied heart at different times of incubation and at different concentrations of sodium. ATP-dependent Ca2+-binding activity of sarcolemma from hypertrophied heart, when measured at different times of incubation and at several concentrations of calcium, was more than the control. Minimal but an equal amount of cross contamination was seen in both control and experimental preparations; however, phosphatidylcholine, phosphatidylethanolamine and phosphatidic acid contents were increased in sarcolemma from hypertrophied hearts. These results suggest that the sarcolemmal Ca2+-transport systems may become adapted during the development of hypertrophy for augmenting Ca2+-efflux from the hypertrophied myocardial cell and this may prevent the occurrence of intracellular Ca2+ overload in a stable form of cardiac hypertrophy.

Adenosine Triphosphate↗

Effect of adrenochrome on adenine nucleotides and mitochondrial oxidative phosphorylation in rat heart.

Effects of adrenochrome, an oxidation product of epinephrine, on myocardial energy production were investigated by studying changes in adenine nucleotide content and mitochondrial oxidative phosphorylation activities in the isolated rat heart. Perfusion of the heart with 50 mg/L adrenochrome induced a marked decline in contractile force within 5 min and this was associated with a rapid decline in the myocardial ATP/AMP ratio. A significant decrease in ATP and ATP/ADP ratio as well as a significant increase in ADP and AMP content was observed at 10 min of perfusion with adrenochrome. Furthermore, mitochondrial oxidative phosphorylation activities were unchanged except that an increase in state 4 respiration and a decrease in RCI value were seen in the heart perfused with adrenochrome for 10 min. Autoradiography of the sections from hearts perfused with 14C-adrenochrome revealed the localization of a significant amount of radioactivity on mitochondria. Adrenochrome at concentrations of 20 mg/L or higher was found to inhibit the oxidative phosphorylation activities of heart mitochondria under in vitro conditions. The depressant effects of adrenochrome on mitochondrial oxidative phosphorylation were additive to those seen with calcium. These data suggest that adrenochrome in the presence of excess calcium in the myocardial cell may impair the process of energy production in mitochondria and this may result in contractile failure of hearts exposed to this cardiotoxic metabolite of epinephrine.

Adenosine Diphosphate↗

Oncocytic carcinoid of the lung.

The case of a 47-year-old man with an oncocytic variant of carcinoid of the lung is reported. Chest radiography disclosed a well-defined round mass in the left upper lobe of the lung. Contrast-enhanced CT demonstrated a homogeneously well-enhanced mass. The oncocytic variant of a typical carcinoid is a rare histological entity, which can be established only by the ultrastructural features of mitochondrial hyperplasia and membrane-bound electron dense granules. Therefore, the definite diagnosis of oncocytic carcinoid tumor necessitates ultrastructural observation.

Carcinoma, Adenoid Cystic↗

Clinicopathological features of lymph node metastasis in early gastric cancer.

From 1979 through 1992, 482 cases with solitary early gastric cancer were resected in the Department of Surgery of the National Kyushu Medical Center Hospital. Among the 482 cases, the incidence of lymph node metastasis was 10.0% (48/482). The features of lymph node metastasis were studied while taking into account the combination of clinicopathological findings of the gastric cancer. Lymph node metastasis was rare in both the differentiated type mucosal cancers and submucosal cancers measuring 20 mm or smaller in size without depression. From these results, for early gastric cancer with the above-mentioned characteristics, either endoscopic therapy or local resection without lymph node dissection is considered to be sufficient treatment to obtain a favorable outcome.

Adult↗

Effects of N-(2-mercaptopropionyl)-glycine on postischemic contractile function in ischemic/reperfused hearts. Dissociation of thiobarbiturate-reacting substance formation and contractile dysfunction.

The present study was undertaken to determine whether N-(2-mercaptopropionyl)-glycine, a membrane-permeable antioxidant agent, improves the ischemia/reperfusion-induced cardiac contractile dysfunction. Rat isolated hearts were subjected to a 35 min global ischemia, followed by a 60 min reperfusion. Ischemia/reperfusion did not result in the recovery of postischemic left ventricular developed pressure. Reperfusion markedly increased the content of the thiobarbiturate-reacting substance in the myocardium. Treatment of the perfused heart with 1 mM of N-(2-mercaptopropionyl)-glycine, either during a 30 min pre-ischemia or during a 30 min pre-ischemia and the first 10 min of reperfusion, resulted in an appreciable recovery of the postischemic left ventricular developed pressure and an attenuation of the increase in thiobarbiturate-reacting substance content. When hearts were treated with the same concentration of the agent only during the first 10 min of reperfusion, the cardiac contractile function was not improved during reperfusion despite the increase in thiobarbiturate-reacting substance content of the reperfused myocardium. These results suggest that the increase in thiobarbiturate-reacting substance content during reperfusion is independent of the postischemic contractile failure.

Animals↗

Beneficial effect on nebracetam on energy metabolism after microsphere-induced embolism in rat brain.

The present study was undertaken to examine the possible therapeutic effects on nebracetam on the energy metabolism of rat brain regions in microsphere-induced, sustained ischemia. Microsphere embolism was induced by injection of 900 microspheres (48 microns in diameter) into the right internal carotid artery of rats, and changes in the energy metabolism of the cerebral cortex, striatum and hippocampus of the right hemisphere were determined without and with nebracetam treatment. Microsphere embolism induced increases in lactate and glucose contents and decreases of ATP and creatine phosphate contents in these regions, suggesting that sustained impairment of cerebral energy metabolism occurred. These changes were gradually reversed with time after the operation. Treatment of microsphere-injected rats with 30 mg/kg of nebracetam, p.o., twice a day, was started one day after the onset of cerebral ischemia. The effects of treatment with nebracetam on cerebral energy metabolites were determined on the 3rd and 7th day after operation. Treatment of microsphere-injected rats with nebracetam significantly improved these variables on the 3rd day after the onset of ischemia, but the improvement was small on the 7th day, except for reversal of the hippocampal ATP content. These results suggest that nebracetam is a possible therapeutic agent for the restoration of cerebral energy metabolism against microsphere-induced, sustained cerebral ischemia.

Adenosine Triphosphate↗