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Biomedical subjects

K Nonaka

Publications and source records attributed to K Nonaka.

At least 235 records · Page 13Linked to original sources

Predominance of T lymphocytes in pancreatic islets and spleen of pre-diabetic non-obese diabetic (NOD) mice: a longitudinal study.

We examined sequential changes in the subsets of mononuclear cells infiltrating the pancreatic islets and splenic lymphocytes in pre-diabetic non-obese diabetic (NOD) mice, an animal model for type I diabetes, using immunofluorescent techniques. In the pancreas, a predominant infiltration by activated T lymphocytes, including helper inducer and cytotoxic suppressor T cells, was observed in the early stage of insulitis. Natural killer cells were also detected in the lesions. Immunoglobulin bearing cells tended to increase in number with the progression of insulitis. T lymphocytes were localized close to islet cells, while immunoglobulin bearing cells appeared adjacent to blood vessels and around T cell clusters. Immunoglobulin deposition or Ia expression on islet cells was not observed. The percentage of splenic T lymphocytes was markedly increased in the initial stage of insulitis as compared with control ICR mice and this elevated proportion of T cells continued throughout the observation period. As for splenic T cell subsets, cytotoxic suppressor T cells were increased in NOD mice. These results suggest that T lymphocytes play an important role in the initiation of insulitis long before the onset of overt diabetes. Moreover, NOD mice seem to have characteristic immunological features different from the BB rat or a reported case with human type I diabetes.

Animals↗

[A report of five cases of multiple cancer with hematologic malignancies].

Five patients with multiple cancers that included hematologic malignancies are described. The incidence of multiple cancers in hematologic malignancies has been 8.8% in the past two and a half years at our hospital. The combinations were: 1) primary bilateral breast cancers and acute monocytic leukemia; 2) breast cancer, malignant lymphoma and gastric cancer; 3) malignant lymphoma and gastric cancer; 4) malignant lymphoma and prostate cancer, and 5) colon cancer and multiple myeloma. Our experience suggests an increasing incidence of multiple cancer in hematologic malignancies.

Aged↗

Effects of intravenously and orally administered cinpropazide on the coronary circulation in unanesthetized and unrestrained dogs.

Cardiovascular effects of cinpropazide (1-(3',4',5'-trimethoxycinnamoyl)-4-(N-isopropylaminocarbonylme th yl)-piperazine maleate) administered i.v. and p.o. were investigated in unanesthetized and unrestrained dogs by means of radiotelemetering system with preceding chronic implantations of an aortic and a venous catheter, Doppler flow probe around circumflex branch in the left coronary artery and subcutaneous ECG electrodes. Intravenous administration of cinpropazide indicated that the drug was much less potent in coronary vasodilating property than newly introduced group of coronary vasodilators. However, the oral administration of this agent efficiently exhibited a remarkable increase in the coronary blood flow, suggesting that this agent has an extremely high bioavailability. It is concluded that cinpropazide is a coronary vasodilator to succeed nifedipine and nicorandil exhibiting an actual increase of coronary blood flow by oral administration in the dog.

Administration, Oral↗

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.

Animals↗

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.

Adult↗

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.

Adolescent↗

Presence of prostaglandin D2, E2 and F2 alpha in rat pancreatic islets.

The presence of prostaglandin (PG) D2, PGE2 and PGF2 alpha was demonstrated in rat pancreas and pancreatic islets by specific radioimmunoassay and their contents were measured separately. The amounts of PGD2, PGE2 and PGF2 alpha in rat pancreas were 16.1 +/- 1.1, 9.48 +/- 2.05 and 4.43 +/- 0.62(2) ng/g tissue, respectively. The amounts of PGD2, PGE2 and PGF2 alpha in rat pancreatic islets were 427 +/- 66, 482 +/- 281 and 479 +/- 41 pg/mg protein, respectively. The syntheses of several PGs from PGH2, a common intermediate for PG production, in islet homogenates were also studied. PGH2 was rapidly transformed into PGD2, PGE2 and PGF2 alpha in almost equal proportion in islet homogenates, and the transformation were proportional to the amounts of the homogenates added in the reaction.

Animals↗

Effects of anesthesia on the electrolyte concentrations in blood and coelomic fluid of the earthworm, Pheretima communissima.

Sodium, potassium, calcium and magnesium concentrations in blood and coelomic fluid of Pheretima communissima under various methods of anesthesia or in the unanesthetized condition were determined. All electrolyte concentrations determined in ethanol-anesthetized earthworms were not significantly different from those in unanesthetized earthworms. Thermal (warming, cooling) anesthesia, urethane and chloretone brought about increases or decreases in some electrolyte concentrations in the blood or coelomic fluid. However, not all electrolytes responded similarly to a method of anesthesia.

Anesthesia↗

Twinning rates and seasonal changes in Görlitz, Germany, from 1611 to 1860.

Old-age twinning rates were evaluated over a period of 250 years (1611-1860), from 80,256 parish records of baptism in a church office in Görlitz, East Germany. Two periods with high and two periods with low twinning rates were observed. Twinning rates were relatively stable in spring and fall, but varied greatly in winter and summer.

Birth Rate↗

Twinning rate by month of mother's birth in Japan.

Records of two hospitals and of an association of mothers of twins were analysed for the years 1924-1980, finding a total of 656,109 and 1185 twin births, respectively. Twinning rates were higher in summer or fall, in general, but these seasonal variations occasionally changed within a short period of years, as in 1973-75 in the Association group. The twinning rate was also affected by the month of mother's birth. It was low among the mothers born around May-July in maternities up to 1960, and these mothers did not show seasonal variation of twin births. The unlike-sexed twinning rate of the mothers born in May-July was also lower than that of the other mothers, and constantly low even at higher maternal ages. A possible explanation for these phenomena is discussed.

Adult↗

Decreased response of epinephrine and norepinephrine to insulin-induced hypoglycemia in diabetic autonomic neuropathy.

The responses of epinephrine, norepinephrine and other counter-regulatory hormones to insulin-induced hypoglycemia were investigated in 5 diabetics who showed signs of autonomic neuropathy, in 7 age-matched diabetics without autonomic neuropathy and in 7 healthy subjects. The presence of autonomic neuropathy was evaluated by decreased beat-to-beat variation in heat rates during hyperventilation or orthostatic hypotension. Catecholamines were determined by a totally automated plasma catecholamine analyzing system using a two-column system of high performance liquid chromatography. Plasma epinephrine and norepinephrine responses to hypoglycemia in diabetics with autonomic neuropathy were significantly lower than those in diabetics without autonomic neuropathy. Plasma glucagon response in diabetics was apparently attenuated compared to normal controls and there was no significant difference in glucagon response between the two patient groups. Other counter-regulatory hormone responses did not differ among the three groups. The data demonstrate that the responses of plasma epinephrine and norepinephrine to insulin-induced hypoglycemia are impaired in diabetics with autonomic neuropathy.

Adult↗

Responses of catecholamines and other counterregulatory hormones to insulin-induced hypoglycemia in totally pancreatectomized patients.

Responses of glucagon, catecholamines, and other counterregulatory hormones to insulin-induced hypoglycemia were evaluated in five totally pancreatectomized patients and six normal subjects. In pancreatectomized patients, plasma glucagon, probably of gastric origin, did not change significantly during hypoglycemia. The responses of epinephrine and norepinephrine were delayed but adequate compared with those in normal subjects. The responses of cortisol and GH were almost as great as those in normal subjects. However, plasma glucose levels did not recover from hypoglycemia normally in these patients. These results suggest that glucagon responses are essential to recover from hypoglycemia and that neither epinephrine nor norepinephrine plays a crucial role in the recovery from acute insulin-induced hypoglycemia in totally pancreatectomized patients.

Adult↗

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.

Adult↗

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.

Animals↗

Food constituents as a cause of variation of C-peptide excretion in the urine.

Since C-peptide immunoreactivity (CPR) is excreted at a much higher rate than insulin in the urine, the urinary CPR (U-CPR) level could be a good measure of pancreatic B-cell function. In 10 normal subjects and 17 patients with non insulin-dependent diabetes mellitus (NIDDM), the 24-hour U-CPR level was 49.6 +/- 4.5 (mean +/- SE) micrograms, and 59.1 +/- 7.9 micrograms, respectively. When measured repeatedly during 4-37 consecutive days, the mean levels of coefficient of variation (c.v.) of 24-hour U-CPRs in each individual in normal and diabetic patients were 23.4 +/- 3.2%, and 39.1 +/- 1.2%, respectively. Thus, the daily fluctuation of U-CPR was considerably large not only in NIDDM but also in normal healthy subjects. In order to investigate factors responsible for these U-CPR variations, we analyzed the effect of food constituents on U-CPR excretion in this paper. In 8 healthy subjects 5-hour U-CPR excretions were measured after ingesting 5 kinds of isocaloric 300 kcal test meals, i.e. glucose, starch, protein, fat, and mixed meal which consisted of equal kcal of starch, protein and fat. Five hour U-CPR excretion after glucose, starch and protein meal ingestion was 9.5 +/- 1.3 micrograms, 13.7 +/- 1.9 micrograms, and 7.4 +/- 0.9 micrograms, respectively. Fat meal induced no increase in U-CPR excretion. After the mixed meal ingestion, 5-hour U-CPR was 8.2 +/- 0.6 micrograms, which was approximately the mathematical average for the U-CPR after 3 meals. We conclude that the cause of variations in the U-CPR excretion may be ascribed not only to the ingested total calories, but also to the nutritional components of the diet. Therefore, care must be taken in reading a daily U-CPR measurement in assessing pancreatic B cell function.

Adult↗