Biomedical subjects
N Kono
Publications and source records attributed to N Kono.
Decreases in hepatic fructose-2,6-bisphosphate level and fructose-6-phosphate,2-kinase activity in diabetic mice: a close relationship to the development of ketosis.
Hyperglycemic mice with streptozotocin diabetes were divided into two groups according to the presence or absence of ketosis. No difference in blood glucose level between two groups was observed in this experiment. However, hepatic fructose-2,6-P2 level and fructose-6-P,2-kinase activity were decreased only in ketotic diabetic mice. Similar decreases in those indices were observed in 48-h starved normal mice. In ketotic diabetes, insulinization for 24 h was required to normalize fructose-2,6-P2 level and fructose-6-P,2-kinase activity, while glucose administration normalized altered fructose-2,6-P2 metabolism in starvation only in 30 min. Hepatic cyclic AMP was increased neither in ketotic nor in non-ketotic diabetic mice. These results indicate that the decrease in hepatic fructose-2,6-P2 level in diabetes is apparently related to the occurrence of ketosis, but not to hyperglycemia. The mechanisms of the decrease in fructose-6-P,2-kinase activity in ketotic diabetes and starvation are discussed.
[Clinical evaluation of serum tissue polypeptide antigen (TPA) in patients with colo-rectal cancer].
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A comparative study on glucagon effect between McArdle disease and Tarui disease.
Pretreatment with glucagon relieved patients with McArdle disease from muscular symptoms during exercise and enhanced exercise performance, though it did not produce any improvement in patients with Tarui disease. The difference in glucagon effect between the two diseases was clearly demonstrated in the bicycle ergometer exercise tests. In addition, the semi-ischemic forearm exercise tests performed after glucagon injection showed that increased lactate production was significantly induced by exercise in McArdle disease, but it was not the case in Tarui disease. In McArdle disease, the augmentation in exercise-induced lactate production was also observed after administration of glucose, or glucose plus insulin, but it was neither observed after administration of insulin alone nor after arginine or epinephrine administration. These findings suggest that the beneficial effect of glucagon in McArdle disease is due to the enhanced utilization of circulating glucose through the muscular glycolytic pathway realized in the coexistence of hyperglycemia and hyperinsulinemia.
Kinetic properties of erythrocyte phosphofructokinase in patients with type VII glycogenosis from two families--close similarity to liver type phosphofructokinase.
The kinetic properties of phosphofructokinases (PFKs) from normal human liver, muscle and erythrocytes, and from erythrocytes of two unrelated patients with type VII glycogenosis (muscle PFK deficiency, McKusick 23280) were analysed in this study. Sensitivity to inhibition by ATP and to inhibition by 3-phosphoglycerate, 2-phosphoglycerate, phosphoenolpyruvate and citrate were quite different for muscle and liver PFKs. The kinetic characteristics of normal erythrocyte PFK were intermediate between those of muscle and liver PFKs. The kinetic constants of erythrocyte PFK of a patient in one family were indistinguishable from those in the other family. In addition, kinetic behaviour of residual PFK activity in erythrocytes from patients in the two families were quite similar to those of normal liver PFK. These results of kinetic analyses provide convincing evidence for the concept that normal erythrocyte PFK consists of muscle and liver type subunits. Residual erythrocyte PFK activity in type VII glycogenosis is thus concluded to reflect the activity of liver type PFK existing in patient's erythrocytes.
Metabolic basis of improved exercise tolerance: muscle phosphorylase deficiency after glucagon administration.
A 26-year-old girl with muscle phosphorylase deficiency had exercise intolerance and experienced an occasional "second wind" phenomenon. Muscle glycogen concentration was about three times the normal level, whereas each glycolytic intermediate below the phosphorylase step was equivalent to only 10% of a normal level. Semi-ischemic forearm exercise tests disclosed no elevation of the venous lactate or pyruvate level, but they showed remarkable increases of serum creatine kinase and ammonia. Glucagon administration markedly augmented exercise tolerance. Forearm exercise after glucagon injection significantly increased venous lactate. Thus, the beneficial effect of glucagon is attributable to blood glucose utilization by muscle.
Insulin and epidermal growth factor stimulate glycolysis in quiescent 3T3 fibroblasts with no changes in key glycolytic enzyme activities.
In order to study the effect of insulin and epidermal growth factor (EGF) on glycolysis in quiescent 3T3 fibroblasts and their mechanisms of action, lactic acid produced by cells and activities of key glycolytic enzymes in cell extracts were determined. Insulin increased lactic acid production; the maximal stimulation occurred at the concentrations above 250 ng/ml and the half-maximal dose was 50 ng/ml. This effect of insulin appeared as early as one hour, and lactic acid production in the presence of insulin linearly increased up to 4 h. The 24-h pretreatment with insulin exhibited no significant effect on the production by cells afterward incubated either with or without insulin. Lactic acid production decreased as the concentration of phloridzin increased. However, insulin stimulation of the production still remained in the presence of phloridzin. Parahydroxymercuribenzoate reduced production only by the equivalent of the increase due to insulin. EGF also increased lactic acid production; this effect occurred at 1 ng/ml and was maximal at 100 ng/ml. The activities of hexokinase, phosphofructokinase and pyruvate kinase in quiescent cells were not increased by insulin, and the affinities for substrates of these enzymes remained unaltered. These findings suggest that glucose uptake is a rate-limiting step in glycolysis in quiescent 3T3 fibroblasts and that the stimulatory effect of insulin on glycolysis is mediated by enhanced glucose entry.
[A successful complete repair of pulmonary atresia with nonconfluent pulmonary arteries in 6-year-old boy].
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Primary carcinoid tumor of the larynx and review of the literature.
Primary carcinoid tumor of the larynx is very rare. This is the fifth case reported in the literature and the first autopsy case of laryngeal carcinoid. The early manifestation of the present case was multiple metastasis to the skin. At autopsy there was a laryngeal tumor associated with widespread visceral and cutaneous metastases. The tumor proved to be carcinoid tumor by histological, histochemical and electron microscopic findings.
Electron microscopic observation of destruction of biliary epithelium in primary biliary cirrhosis.
Electron microscopic studies of the intrahepatic biliary tree in 16 patients with primary biliary cirrhosis (PBC) disclosed four types of biliary epithelial injury suggesting cell death in the ducts: 1) coagulative and 2) lytic necrosis without detachment of affected cells from the biliary epithelial layer, and 3) apoptosis and 4) detachment of several adjoining biliary cells from the basement membrane and neighboring biliary cells. Lesions 1), 2) and 3) were also found in livers with extrahepatic cholestasis without bile duct loss, and 1) and 2) were found in PBC livers irrespective of the degree of bile duct loss. 3) was rare and mostly confined to bile ductules, when present. By contrast, 4) was only observed in PBC, especially in livers with a moderate degree of bile duct loss in which extensive bile duct destruction appeared to be progressing. Detached biliary cells in lesion 4) were occasionally in contact with and/or surrounded by migrating lymphocytes with pseudopod formation, suggesting lymphocyte-target cell interactions. It therefore seems possible that epithelial detachment is an important ultrastructural lesion associated with extensive bile duct destruction in PBC livers.
Kinetic properties of mutant enzymes in erythrocyte phosphofructokinase deficiency and erythrocyte pyruvate kinase deficiency.
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Effect of insulin on glycolysis in rat diaphragm muscle: comparison with the effect in quiescent 3T3 fibroblasts.
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[Genetic and biochemical studies in familial incidences of Kartagener's syndrome].
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[Clinical investigation of intratumoral OK-432 administration].
The clinical effect of intratumoral administration of OK-432 was evaluated. The patients with nonresectable advanced cancer were divided into three groups according to administration method of OK-432 at laparotomy: Group I; Intratumoral administration, Group II; Scattering to the abdominal cavity, and Group III; No OK-432, administration. Improvement in suppression of tumor progression was more frequently noticed in the Group I compared to the Group II and III, but there was no significant difference in terms of survival time and rate among the three groups.
Conversion of percutaneous transhepatic cholangiodrainage tube into an endoprosthesis by means of burying its external tip in the subcutaneous tissue.
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Ultrastructural changes of bile duct epithelium in primary biliary cirrhosis in relation to progression of bile duct loss.
Using wedge liver biopsies from patients with primary biliary cirrhosis (PBC), ultrastructural features of the intrahepatic bile ducts in livers with slight or no bile duct loss were compared with those in livers with advanced bile duct loss and in extrahepatic cholestasis (EHC). Most changes in the biliary epithelium in PBC were similar to those in EHC. Microvillous loss and bleb formation, mitochondrial damage and increase in endoplasmic reticulum and ribosomes were found in PBC irrespective of the degree of bile duct loss, and also in EHC. These changes were present almost equally at any level of the biliary tree, and are presumed to represent a variety of non-specific lesions of biliary epithelial cells. As the loss of bile ducts in PBC progressed, cytoskeletal filaments and cytophagosomes increased in number and basement membranes were more thickened and reduplicated. These changes were more or less conspicuous in smaller branches of the biliary tree, and were also prominent in EHC. They might be causally related to the bile flow disturbance in the liver. Lateral intercellular spaces were irregularly dilated and contained osmiophilic membranous and/or granular material, similar to that found in duct lumena, within and without the basement membrane, and in the cytoplasm of periductal macrophages. Furthermore, pinocytotic vesicles were increased in the biliary cytoplasm facing periphery. These findings suggest possible alteration of the permeability of biliary epithelial cells, probably in the direction from the lumena to the periductal tissue. Such changes were found in PBC livers with virtual absence of bile duct loss, and the significance of this phenomenon is discussed.
Clinical results of cardiopulmonary bypass with selective cerebral perfusion for aneurysm of the ascending aorta and the aortic arch.
The purpose of this report is to describe our experience using cardiopulmonary bypass with selective cerebral perfusion in 10 patients whose aneurysms required cross-clamping the aorta and brachiocephalic vessels. Cerebral perfusion was carried out with individual roller pumps. Flow rate was 11.2 +/- 4.8 ml per kilogram of body weight per minute to the right axillary artery, 8.5 +/- 1.0 to the right common carotid artery, 7.0 +/- 2.0 to the left common carotid artery, and 3.9 to the left subclavian artery. All the patients came off bypass smoothly, and only 3 required small amounts of inotropic agents postoperatively. One patient with mycotic aneurysm died in the fourth postoperative week of massive bleeding due to disruption of the suture line. No cerebral complications were experienced. The operative results of this series suggest the usefulness of cardiopulmonary bypass with selective cerebral perfusion, and reasonably favorable outlook for patients with aneurysm involving the aortic arch and the ascending aorta.