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Biomedical subjects

K Nonaka

Publications and source records attributed to K Nonaka.

At least 253 records · Page 14Linked to original sources

Genetic variation and craniofacial growth in inbred rats.

There has been no experimental study clarifying the contribution of genetic variation to craniofacial growth on a longitudinal basis, although its importance is generally accepted. Utilizing diallel crosses of five strains of inbred rats, the present study concerns an estimation of the contribution genetic variation makes to the longitudinal change of craniofacial size. The overall sizes of craniofacial complex components of F1-offspring rats were investigated postnatally by means of roentgenographic cephalometry, and quantitative genetic analysis was performed by the method of Wearden [1964]. It was revealed that the relative contributions of the genetic and environmental components to total variance in craniofacial size varied with age and that the genetic component of variance significantly increased until the 80th day. On the other hand, the maternal component of variance showed the maximum value during the early periods of postnatal growth (ie, the 10th to 25th day), gradually declining thereafter to a very small amount by the 80th day. The environmental component of variance increased slightly and gradually with age through the experimental period. In conclusion it appeared that genetic variation became more significant during longitudinal growth of the craniofacial complex as the maternal effects diminished.

Age Factors↗

Effects of antibiotics, minocycline and ampicillin, on human sleep.

The effects of two kinds of antibiotics, minocycline (MNC) and ampicillin (AB-PC), on human sleep were investigated on 19 healthy male students to test for a relationship between human sleep and protein synthesis. These drugs and placebos were capsulated identically in appearance and were given to the subjects using the single blind method. MNC has been proven to prevent protein synthesis whereas AB-PC does not inhibit protein synthesis, and both antibiotics are commonly used in clinical practice. With the administration of a single dose of 200 mg of MNC, an apparent decrease in slow wave sleep (SWS) was revealed on the drug night and the effects lasted through the following two consecutive nights being given a placebo. REM sleep was not reduced on all the recording nights. On the other hand, both SWS and REM sleep were not reduced with the administration of a single dose of 500 mg of AB-PC. These results are different from those previously obtained from animal experiments since many kinds of protein synthesis inhibitors have been proven to suppress mainly REM sleep in animals. It might be supposed that the species difference may be responsible for this difference, and that some proteins or polypeptides induce human sleep, especially SWS.

Adult↗

Glucose dependent stimulation by prostaglandin D2 of glucagon and insulin in perfused rat pancreas.

Effects of prostaglandin D2 on pancreatic islet function in perfused rat pancreas were examined in comparison with those of prostaglandin E2, which has hitherto been suggested to be a modifier of pancreatic hormone release. In the presence of 2.8 mM glucose, only glucagon release was strongly stimulated by 14 microM of prostaglandin D2, while release of both glucagon and insulin was augmented by 14 microM of prostaglandin E2. When the glucose concentration was elevated to 11.2 mM, insulin release was accelerated by 14 microM of prostaglandin D2 but there was no effect upon glucagon release. Again, release of both glucagon and insulin was augmented by 14 microM of prostaglandin E2 in the presence of 11.2 mM of glucose. The regulation of glucagon and insulin release through prostaglandin D2 is apparently adapted to glycemic changes, and may be a physiological modulator of pancreatic islet function.

Animals↗

A study of the sex ratio of first-born according to the mother's month of birth.

The male-to-female sex ratio at birth of the first-born babies delivered in Japan to mothers aged 25 years or less was investigated in two groups: a hospital group and a questionnaire group. The sex ratio fluctuated according to their mother's month of birth. Between 1924 and 1928, the sex ratio of the offspring of the mothers born in March-May in both groups was significantly higher than that of the other mothers. We speculate about the relationship between the sex ratio at birth and the mother's month of birth.

Adult↗

Inhibition of pancreatic exocrine secretion and augmentation of the release of gut glucagon-like immunoreactive materials by intraileal administration of bile in the dog.

The effect of intraileal instillation of bile, a stimulant of gut glucagon-like immunoreactive materials (gut GLI), on secretin-stimulated pancreatic secretion was examined in anesthetized dogs. Intraileal bile significantly inhibited the flow rate of secretin-stimulated pancreatic secretion. The inhibition of pancreatic secretion was accompanied by an elevation of plasma concentration of gut GLI. Taking the inhibitory effect of glucagon on pancreatic exocrine secretion into consideration, it could be reasonably postulated that gut GLI may be a mediator of bile-induced ileal inhibition of pancreatic exocrine function.

Animals↗

Modulation by prostaglandin D2 of glucagon and insulin secretion in the perfused rat pancreas.

Effects of prostaglandin (PG) D2 on insulin and glucagon secretion from perfused rat pancreas were examined. In the presence of 2.8 mM glucose, only glucagon release was strongly stimulated by 14 microM of PGD2. When the glucose concentration was elevated to 11.2 mM, insulin release was accelerated by 14 microM of PGD2 but there was no effect upon glucagon release. Both glucagon and insulin releases induced by 19 mM arginine with PGD2 were not different from those without PGD2 in the presence of 2.8 mM glucose. But in the presence of 11.2 mM glucose, glucagon release induced by 19 mM arginine was augmented by 14 microM PGD2. Since the distribution of PGD2 has been reported to be in neuroendocrine organs, these results suggest that PGD2 is a possible candidate as a modulator in the neural control of endocrine pancreas.

Animals↗

Effect of intraluminal bile or bile acids on release of gut glucagon-like immunoreactive materials in the dog.

The true biological role of gut glucagon-like immunoreactive materials (gut GLI) is still unknown, although the stimulatory effect of intraluminal nutrients on the secretion of gut GLI has been described. The present authors, using the canine intestinal loop prepared from the terminal portion of the ileum, investigated how gut GLI would respond to digestive juice or its components. When bladder bile collected from another dog and diluted to 10% in saline was instilled into canine ileal loop, gut GLI in a branch of regional mesenteric vein was elevated significantly. Cholic acid suspended in saline (0.25 g/50 ml) also stimulated gut GLI secretion in the similar pattern to that of bile administration. On the other hand, 154 mM NaHCO3 which is a major inorganic component of pancreatic juice did not affect the venous level of gut GLI.

Animals↗

Prevalence of diabetic retinopathy and distribution of its severity among patients of a university clinic of diabetes in Osaka.

We have been following longitudinal changes of diabetic retinopathy by periodic fundoscopy in patients at our out-patient clinic for diabetes mellitus. In this study, we reviewed the prevalence of diabetic retinopathy and the distribution of its severities. Funduscopic examinations for retinopathy were performed on 242 patients. They ranged in age from 13 to 84 years (52.9 +/- 0.9, mean +/- s.e.). Duration of diabetes ranged from 1 to 31 years (10.7 +/- 0.4). Forty patients were treated with diet alone, 112 with oral hypoglycemic agents and 90 with insulin administration. No retinopathy was found in 83 patients (34%), background retinopathy in 113 (47%), preproliferative retinopathy in 24 (10%) and proliferative retinopathy in 17 (7%). Five patients (2%) were blind. Twenty-seven patients (60%) of 45 with a less than 5-year duration of diabetes were apparently without retinopathy, while the incidence of proliferative retinopathy increased in proportion to the duration. Fasting plasma glucose and glycosylated hemoglobin levels were higher in the patients with proliferative retinopathy than in any other group. All of the blind patients had a long history of untreated diabetes. Whether diabetic control assessed by glycosylated hemoglobin influences the progression of retinopathy could not be demonstrated by a 2-year observation. Further analysis based on a longer duration is needed in this respect.

Adolescent↗

Comparison of diurnal serum insulin levels during short term treatments with sulfonylurea and with insulin in non-insulin dependent diabetes.

Nine non-insulin dependent type diabetic patients were hospitalized and place on the standard diabetic diet throughout this study period. (25 cal/kg ideal weight/day). After three days of diet therapy alone, 5 mg of glibenclamide was given orally for three days, followed by an interval of four days without medication. 16 units of lente insulin was then administered subcutaneously for three days. The diurnal levels of plasma glucose (PG) and serum immunoreactive insulin (IRI) were determined on the third day of each treatment, and the integrated areas below the curves of the diurnal profile of PG and IRI were compared. The mean fasting PG level before treatment was 200 +/- 21 mg% (mean +/- SE). The initial PG area during diet therapy alone, (4,245 +/- 669 mg . h/dl) decreased significantly to similar levels both by glibenclamide (3, 317 +/- 384 mg . h/dl, P less than 0.05) and by lente insulin (3,177 +/- 552 mg . h/dl, P less than 0.01). The IRI area increased from 187 +/- 24 micromicron . h/ml during diet therapy alone to 296 +/- 65 micromicron . h/ml by glibenclamide (P less than 0.01), and to 267 +/- 43 micromicron . h/ml by lente insulin (P less than 0.05). There was no significant difference between glibenclamide and lente insulin treatments either in PG area or IRI area. These finding suggest that the hypoglycemic effect of glibenclamide treatment in the short term is mainly, if not entirely, due to augmented endogenous insulin secretion.

Adult↗

Effects of iodide and propylthiouracil on the release of 3,5,3'-triiodothyronine and of cyclic adenosine 3',5'-monophosphate from perifused rat thyroids.

We have established a perifusion system using rat thyroid. With this system, we analyzed the effects of TSH, 3-isobutyl-1-methylxanthine (IBMX) and iodide on the release of T3 and of cAMP, paying special attention to the relation between the release of the two substances. During perifusion, which was continued for 7 h, T3 release increased progressively with time and in a dose-related manner when TSH was added at concentrations of 0.1-10 mU/ml. However, cAMP release was unappreciable even in the presence of 10 mU/ml TSH. The release of T3 and cAMP was markedly enhanced by 3 x 10(-4) M IBMX. When iodide was added, a marked increase in cAMP release was unexpectedly observed. However, a slight but significant suppression of TSH-stimulated T3 release was shown with 1 x 10(-3) M iodide. TSH-stimulated T3 release was almost completely inhibited by 1 x 10(-3) M 6-n-propyl-2-thiouracil, but such a complete inhibition did not occur with 2-mercapto-1-methylimidazole. The cAMP release stimulated by IBMX was not affected by 6-n-propyl-2-thiouracil, but that stimulated by iodide was effectively inhibited. The present studies indicate that TSH and IBMX enhance T3 release, but only IBMX increases cAMP release. Iodide also results in a marked increase in cAMP release but does not affect T3 release from unstimulated thyroid and inhibits T3 release from TSH-stimulated thyroid. We suggest that there is not necessarily any close correlation between T3 release and cAMP release into perifusates of the rat thyroid.

1-Methyl-3-isobutylxanthine↗

Islet-activating protein (IAP) reduces bethanechol-stimulated release of pancreatic polypeptide in the dog.

The effect of islet-activating protein (IAP) purified from culture medium of Bordetella pertussis was examined in dogs. This was assessed by the levels of pancreatic polypeptide (PP) as well as the responses of plasma insulin and glucagon to a parasympathomimetic agent, bethanechol. Plasma responses of these pancreatic hormones were measured before and 5 days after IAP injection. Although IAP had no significant effect on the bethanechol-stimulated increase in plasma glucose, insulin and glucagon, the PP response to bethanechol was significantly reduced after IAP treatment compared with that before IAP (p less than 0.05). In conclusion, IAP significantly and selectively reduced bethanechol-stimulated PP release in the dog although the mechanism remained to be elucidated.

Animals↗

Effect of the discontinuation of long-term sulfonylurea treatment on blood glucose and insulin secretion in noninsulin-dependent diabetes mellitus.

The mechanism of the hypoglycemic action of sulfonylureas during long-term treatment was investigated in twenty-four patients with noninsulin-dependent diabetes mellitus treated for 1.5 to 19 yr in the out-patient clinic. The subjects received the first oral glucose tolerance test (OGTT) while on sulfonylureas and the second OGTT one month after their withdrawal. As the degree of elevation of the fasting plasma glucose level after withdrawal varied, the subjects were classified into two groups. Fourteen subjects showing an increase of more than 15 mg/dl were arbitrarily designated as group I, and the rest as group II. The mean fasting plasma glucose of group I was 134 +/- 4 mg/dl (mean +/- SE) and 194 +/- 14 mg/dl with and without sulfonylureas, respectively. Group II did no exhibit any significant change in fasting plasma glucose. A mean fasting serum IRI of either group was not changed. In group I, a mean glucose area of 807 +/- 31 mg . h/dl on OGTT increased significantly to 1121 +/- 72 mg . h/dl (p less than 0.001) and, the same time, a mean IRI area decreased significantly from 102 +/- 10 microU . h/ml to 73 +/- 7 microU . h/ml (p less than 0.001). The ratio of IRI area to glucose area, which might indicate the responsiveness of pancreatic B cells to hyperglycemia, was reduced on an average by 48% in group I. However, group II showed no significant change in the mean value of the glucose area, IRI area or the ratio one month after the discontinuation of sulfonylurea treatment. These findings suggest that the insulinotropic action of sulfonylureas is maintained even after long-term treatment and contributes to their antidiabetic effect.

Adult↗

Impaired response of human pancreatic polypeptide to insulin-induced hypoglycemia in chronic pancreatitis without diabetes mellitus.

In order to clarify the pancreatic endocrine functions in mild chronic pancreatitis, the response of insulin to oral glucose load and the response of glucagon and human pancreatic polypeptide (HPP) to insulin-induced hypoglycemia were investigated in five normal controls and eight patients with chronic pancreatitis but without diabetes mellitus. Although insulin and glucagon responses in patients with chronic pancreatitis tended to be lower than those in normal subjects, the differences between the two groups were not statistically significant. In contrast, HPP response to hypoglycemia in the patients was markedly impaired and significantly lower than that in normals (p less than 0.02). This finding indicates that the impairment of HP response is the earliest and most definite manifestation among pancreatic endocrine abnormalities in chronic pancreatitis.

Adult↗

Various phenotypes of diabetes mellitus at ultimate outcome of acutely developed diabetic state induced by viral infection.

For 4 to 8 years we followed up 3 diabetic patients in whom the onset of diabetes seemed to be closely related to the well-documented Epstein-Barr virus infection (Case 1) or Coxsackie B4 virus infection (Case 2, 3). Although all developed acute ketosis-prone diabetes in the convalescent stage of the viral infections, the subsequent clinical courses were quite different from each other. Case 1 has remained consistently insulin-dependent and associated with positive islet cell antibody, gastric parietal cell antibody, thyroglobulin hemoagglutinating antibody and thyroidal microsomal hemoagglutinating antibody. Case 2 restored normal glucose tolerance. Case 3 has become noninsulin-dependent diabetes mellitus after a 6 year interval. Thus, it is reasonably presumed that virus could be responsible for the occurrence of different phenotypes of diabetes.

Acute Disease↗