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Biomedical subjects

K Kosaka

Publications and source records attributed to K Kosaka.

At least 397 records · Page 22Linked to original sources
PubMed1980

Decline of postheparin plasma lipoprotein lipase in acromegalic patients.

Lipoprotein lipase and hepatic triglyceride lipase in postheparin plasma were measured in seven patients with active acromegaly by an immunochemical method utilizing antiserum prepared against hepatic triglyceride lipase. A mild or moderate hypertriglyceridemia was shown, with plasma triglyceride concentrations between 156 and 544 mg/dl. Lipoprotein lipase was found to be decreased in all patients (p less than 0.001). Hepatic triglyceride lipase was also low in these patients (p less than 0.001). We speculate that acromegalic hypertriglyceridemia is mediated, at least in part, by the decline in lipoprotein lipase and possibly by the decline in hepatic triglyceride lipase activities.

Acromegaly↗
PubMed1980

Detection and assessment of human tumours producing granulocyte-macrophage colony-stimulating factor (GM-CSF) by heterotransplantation into nude mice.

Production of granulocyte-macrophage colony-stimulating factor(s) (GM-CSF) by human tumours was investigated using heterotransplantation of a number of different tumours in nude mice. An increase in granulocyte numbers (> 20,000/mm3) in the peripheral blood of nude mice accompanied the growth of 9 of the 25 transplanted tumours. GM-CSF activity tested against normal human marrow cells was relatively high in 6 of these 9 tumours. Moreover there was either weak activity or none at all in 14 of the 16 tumours that failed to cause a definite granulocytosis. The correlation between granulocytosis and GM-CSF activity was 0.36, which was statistically significant (P < 0.01). These findings indicate that the transplantation of human tumours into nude mice can provide a useful tool for detection and characterization of granulopoietic factors derived from the tumours.

Animals↗
PubMed1980

Monolayer culture of human fetal and adult pancreas. Static and dynamic studies of insulin release in vitro.

Insulin release from pancreata of human fetuses aged 4 to 9 months and from adult pancreata were studied in monolayer cell culture by static incubation and perifusion technique. Fetal pancreata at the midterm of gestation (4 to 6 months) showed no response of insulin release to glucose. In a case of 9 months-old fetus, in which a small but significant increase of insulin release was observed with glucose (300 mg/ml). Tolbutamide (100 microgram/ml) had no effect on insulin release from all the pancreata of fetuses tested. Caffeine (5 and 10 mM), a phosphodiesterase inhibitor, potentiated insulin release by itself and also induced the glucose-stimulated insulin release from the fetal pancreata in the dose related manner. Glucagon (2 microgram/ml), L-isoproterenol (2 microgram/ml), L-arginine (10 mM) and L-leucine (10 mM) failed to induce any increase of insulin release from fetal pancreata. In the presence of caffeine, the significant increase of insulin release from fetal pancreata was observed with L-leucine, but not with L-arginine. There was no evidence of the maturation of B-cells during the culture periods (4 to 8 days), probably lacking the key steps of stimulus-secretion couplings in relation to adenylate cyclase-cyclic AMP system. By contrast, glucose (100 and 300 mg/100 ml), tolbutamide (100 microgram/ml), L-arginine (10 mM) and caffeine (5 mM) caused a significant increase of insulin release from adult pancreata. Thus, the development of human pancreatic B-cells seems to depend substantially on gestational age, being ready to equip most machinary of insulin release before delivery.

Arginine↗
PubMed1980

Effects of neuraminidase treatment on solubilized insulin receptor.

Neuraminidase treatment of triton-solubilized insulin receptors from rat fat cell membranes caused release of sialic acid and changed the isoelectric point (pI) of the insulin receptor from 4.7 to 5.6. Neuraminidase had no effect on the number or affinity of insulin receptors. These results indicate that the insulin receptor contains sialic acid, but that this sialic acid is not involved in the binding reaction.

Adipose Tissue↗
PubMed1980

Isolation and partial characterization of two immunologically similar vitamin D-binding proteins in rat serum.

Two immunologically similar, probably identical, binding proteins for vitamin D and its metabolites (DBP1 and DBP2) were isolated separately from rat serum after approximately 180-fold purification by novel procedures using Blue Sepharose CL-6B chromatography. The freshly purified DBP1 and DBP2 each showed a single band of protein on polyacrylamide gel electrophoresis, and had alpha-mobility, although DBP1 moved slightly faster than DBP2. DBP1 and DBP2 had the same molecular weight, which was estimated as approximately 54,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The isoelectric points of DBP1 and DBP2 were estimated as 4.9 and 5.0, respectively, from the results of isoelectric focusing experiments. DBP1 and DBP2 both appeared to have one binding site for 25-hydroxyvitamin D3 per molecule of protein, with apparently similar association constants at 4 degrees C of 5--7 x 10(9) M-1. The amino acid compositions of DBP1 and DBP2 were also determined and compared. A monospecific antiserum against rat DBP2 was prepared in a rabbit and was used for immunological studies of rat DBP. On double immunodiffusion, anti-DBP2 antiserum produced precipitin lines of complete reaction-of-identity against the purified DBP1, the purified DBP2, and rat whole serum. There was no immunological cross-reactivity between rat DBP and sera from man, dog, and rabbit, but mouse serum showed a pattern of partial identity with rat DBP. When rat serum samples were analyzed by immunoelectrophoresis using anti-DBP antiserum, three patterns of precipitin line were observed: a pattern showing the existence of only DBP1, designated as DBP 1-1; a pattern showing the existence of only DBP2, designated as DBP 2-2; and a pattern showing the existence of both DBP1 and DBP2, designated as DBP 2-1. Using single radial immunodiffusion assay for rat serum DBP, the mean (+/- S.D.) serum DBP concentrations were found to be 461 +/- 59 microgram/ml in adult male rats and 328 +/- 16 microgram/ml in adult female rats, and the difference was significant (p < 0.001). In molar terms, DBPs are present in normal rat serum in large excess relative to vitamin D and its metabolites, and most of the serum DBP, therefore, circulates as apo-DBP, not containing a bound molecule of vitamin D or of its metabolites. The immunoprecipitation studies of DBP in rat serum showed that DBPs were common main transport proteins for naturally occurring vitamin D and its metabolites, and that DBP played some, but not a principal, role in the transport of synthetic 1 alpha-hydroxyvitamin D3.

Amino Acids↗
PubMed1980

HLA-DRw3 in juvenile onset diabetes mellitus in Chinese.

Thirty-nine juvenile onset diabetes mellitus (JOD) patients and 57 healthy Chinese were HLA-typed in Taiwan. The incidence of HLA-DRw3 was significantly increased in patients when compared with the control group (R.R. = 5.8, P = 0.0027). The frequencies of HLA-B17, which showed linkage disequilibrium with DRw3, and Bw54 were increased in patients, but these increases were not significant because of the small number tested. The DR antigen associated with JOD was the same among Chinese and Caucasians, which suggested that at least one of the susceptibility genes to JOD would be commonly in linkage disequilibrium with DRw3 in the two populations.

Adult↗
PubMed1980

Localized blastoma preceding blastic transformation in Ph1-positive chronic myelogenous leukaemia: morphological and cultural studies of the transformation event.

In a patient with Ph1-positive chronic myelogenous leukaemia (CML), the development of a localized blastoma preceding generalized blastic transformation was accompanied by a reduction of granulocyte-macrophage (GM) colony forming capacity in agar of bone marrow cells as well as an increase in peripheral neutrophil alkaline phosphatase (NAP) scores. Successful transplantation of the blastoma cells into nude mice enabled extensive studies of the cell properties. The blastoma cells were double Ph1-positive cells which did not respond to human granulocyte-macrophage colony-stimulating factor (GM-CSF), and were similar to cells demonstrated in spleen and bone marrow at the terminal stage of the patient's illness. These observations clearly support the case for sequential studies of colony formation in vitro as a useful test for the early detection of disturbances in marrow function that may occur before generalized blastic transformation. Studies of the properties of the blastoma cells also provide some insight into possible mechanisms for the transformation event.

Aged↗
PubMed1980

Insulin receptor function and insulin effects on glucose metabolism in adipocytes from ventromedial hypothalamus-lesioned rats.

To investigate the mechanism of the development of insulin resistance in hypothalamic obesity, we studied insulin binding, glucose transport, and glucose oxidation in adipocytes from ventromedial hypothalamus (VMH)-lesioned rats 1 and 2 weeks after injury. One week after injury, insulin binding and insulin-stimulated glucose oxidation were increased, but insulin-stimulated glucose transport was similar to control. Two weeks after injury, insulin binding and insulin-stimulated glucose transport were similar to control, but insulin-stimulated glucose oxidation was decreased. Thus, cellular insulin responsiveness was increased in adipocytes from VMH-lesioned rats 1 week after injury; this increase in insulin responsiveness was due mainly to the increased intracellular glucose metabolism. On the other hand, cellular insulin resistance existed in adipocytes from VMH-lesioned rats 2 weeks after injury; this insulin resistance was also due mainly to a defect in intracellular glucose metabolism.

Adipose Tissue↗
PubMed1980

Isoproterenol-stimulated C-peptide and insulin secretion in diabetic and nonobese normal subjects: decreased hepatic extraction of endogenous insulin in diabetes.

After the iv injection of 2 micrograms isoproterenol, peripheral plasma insulin and C-peptide concentrations were measured in 16 nonobese normal subjects and 53 maturity-onset diabetic subjects. Basal insulin (P < 0.01) and C-peptide (P < 0.05) levels were increased in obese diabetic subjects compared to nonobese normal subjects. Isoproterenol-stimulated insulin (P < 0.01) and C-peptide (P < 0.05) increments were increased in obese diabetic subjects compared to nonobese diabetic subjects. Hepatic insulin extraction, measured by comparing the ratios of insulin increment to C-peptide increment after isoproterenol injection, was decreased in both nonobese and obese diabetics compared to normals (P < 0.05). No significant differences in the ratios were found between nonobese and obese diabetics or between patients on diet or sulfonylurea therapy. Age, sex, duration of disease, familial predisposition to diabetes, and diabetic retinopathy did not influence the ratios. Isoproterenol-stimulated C-peptide increments (P < 0.05) and fasting blood glucose levels (P < 0.05) were decreased in diabetics showing decreased hepatic insulin extraction compared to diabetics with normal hepatic insulin extraction. Isoproterenol-stimulated insulin increments in diabetics showing decreased hepatic insulin extraction were higher than in normals (P < 0.05). These studies indicate that hepatic insulin extraction decreases in nonobese and obese diabetic subjects. It might be postulated that the lesser amount of secreted insulin is able to show biological activities more efficiently in diabetics with decreased hepatic insulin extraction.

Adult↗
PubMed1980

Studies of plasma beta-N-acetylglucosaminidase activity in experimental and clinical diabetes mellitus.

Plasma beta-N-acetylglucosaminidase (NAG) activity was measured in streptozotocin diabetic rats, in non-diabetic rats during starvation and refeeding, and in diabetic patients and normal subjects. The enzyme activity increased significantly in the diabetic rats and in the starved non-diabetic rats. The activity decreased markedly after insulin injection in diabetic rats and after refeeding in non-diabetic rats. The plasma NAG activity (532 +/- 24 nmole/hr/ml, M +/- SE) in 21 diabetics with FBS value less than 100 mg/dl was higher than the enzyme activity (455 +/- 15) in 42 normal subjects (p < 0.01), supporting the idea that a more intensive treatment is necessary to normalize the metabolic derangement of diabetes. There was no significant difference between diabetics with and without microangiopathy. While the influence of age and abnormal liver function was noted, there was no correlation between the NAG activity and the platelet adhesiveness or between the NAG activity and the plasma triglyceride. The results suggest that the plasma NAG activity increases in diabetes mellitus, either with microangiopathy or not. The reason for the failure to demonstrate a significant correlation between the total plasma NAG activity and microangiopathy is discussed. The analysis of the subfractionation of the plasma NAG may be necessary to disclose a significant correlation with microangiopathy.

Acetylglucosaminidase↗
PubMed1980

The relationship of intracytoplasmic movement of beta granules to insulin release in monolayer-cultured pancreatic beta-cells.

To study the mechanism of insulin release, we examined beta-granule movement in the cytoplasm of monolayer-cultured B-cells. The majority of the granules do not move, while about 2% of the granules moved per minute. The velocities of 90% of the moving granules exceeded 0.4 micrometer/s and showed saltatory type of movement. This movement may have a role in transport of the beta granule from Golgi to B-cell membrane. We studied the mechanism of this movement using colchicine. Granule movement decreased exponentially by treatment with colchicine (10(-6) M to 10(-4) M). Almost 60 min was necessary to get a full inhibitory effect of colchicine on granule movement. Colchicine (10(-8) M to 10(-4) M) inhibited insulin release in a dose-dependent manner. Maximum inhibition of insulin release (by about 40%) by colchicine (10(-4) M) required 60 min. Granule movement also decreased when insulin release was inhibited by lowering glucose from 16.5 mM to 2.7 mM. Thus, granule movement participates in the mechanism of insulin release and may be related to the microtubular system.

Animals↗
PubMed1980

The potentiating effect of an alpha-adrenergic blocking agent (E-643) on the action of bronchodilators.

The effect of 2-[N-(n-butyloyl)homopiperazin-N'-yl]-4-amino-6,7-dimethoxy quinazoline hydrochloride (E-643), a new alpha-adrenergic receptor blocking agent, on the relaxing responses and on the change of cyclic AMP and cyclic GMP contents in guinea pig tracheal (GPT) tissues induced by various bronchodilators was examined. The relaxing responses and the cyclic AMP and cyclic GMP contents in GPT induced by isoprenaline, adrenaline, prostaglandin E2 and chlorprenaline were markedly enhanced with continuous infusion of E-643. These results may suggest that E-643 can be used together with various bronchodilators for the treatment of chronic obstructive pulmonary diseases.

Adrenergic alpha-Antagonists↗