Search PubMed⌕ Search

Biomedical subjects

J Simon

Publications and source records attributed to J Simon.

At least 361 records · Page 20Linked to original sources

Insulin binding and receptor tyrosine kinase activity in rat liver and skeletal muscle: effect of starvation.

Insulin binding and insulin receptor kinase activity were measured in solubilized and partially purified receptor preparations from liver and skeletal muscles of rats that were either fed a standard diet or subjected to a 72-hour fasting period. Insulin binding capacity was increased in both tissues from fasted rats as determined by Scatchard analysis. The affinity of the receptors was not modified by fasting. Affinity labeling of the alpha-subunit of insulin receptors also suggested an increase in the number of insulin receptors in both tissues. The ability of insulin to stimulate the autophosphorylation of the beta-subunit as well as the phosphorylation of the artificial substrate Glu80-Tyr20 was significantly impaired in liver from fasted rats and by contrast unchanged in skeletal muscles. These findings indicate that in rats, fasting produces changes in insulin receptor kinase activity in liver but not in muscle. The physiological significance of this tissue-specific regulation of receptor kinase activity in relation to insulin action during fasting remains to be established.

Affinity Labels↗

Effects of cysteamine administration on plasma concentration of metabolites, pancreatic glucagon and insulin in the chicken.

1. The effects of subcutaneous injection of cysteamine (2-mercaptoethylamine, 300 mg/kg) were investigated in 5-6 week-old chickens. 2. In the short term (1 hr), cysteamine increased plasma levels of glucose, free fatty acids and insulin, and decreased that of alpha-amino non protein nitrogen. 3. In a longer term (17-24 hr), cysteamine increased the plasma level of glucose, did not modify those of alpha-amino non protein nitrogen, insulin and glucagon and decreased that of free fatty acids. 4. The disposal of an oral glucose load was impaired and the glucose-induced inhibition of pancreatic glucagon and stimulation of insulin release were blunted 17 hr after cysteamine administration. 5. Therefore, cysteamine exerts multiple effects on chicken pancreatic islet cells.

Animals↗

Effect of isoproterenol on lipid metabolism and prostaglandin production in cultures of newborn rat heart cells, under normoxic and hypoxic conditions.

Catecholamines are known to exert deleterious effects on heart cells and to provoke biochemical alterations similar to those observed during myocardial infarction. In order to investigate the mechanisms of these effects, we have studied in cultures of muscle (M) and fibroblast-like (F) cells derived from newborn rat hearts, the action of isoproterenol on membrane lipid metabolism and on prostaglandin production. We showed in F cells that beta-agonist stimulation produced a striking loss of membrane phospholipids and a moderate hydrolysis of cell triglycerides. In addition, isoproterenol treatment induced a significant stimulation of the secretion of prostacyclin but not of prostaglandin E2 by F cells. None of these effects were potentiated by oxygen deprivation. In contrast, M cells, which are sensitive to ischemia, failed to respond to isoproterenol treatment. These results suggest that catecholamines and hypoxia may exert combined deleterious effects on heart tissue by acting separately on the different target cells in vivo.

Animals↗

Prognostic factors in patients with primary transitional cell carcinoma of the upper urinary tract.

A total of 50 patients with primary transitional cell carcinoma of the upper urinary tract underwent deoxyribonucleic acid ploidy characterization by flow cytometric analysis of paraffin embedded specimens. The primary tumor was diploid in 29 patients (58%) and aneuploid in 21 (42%). Aneuploidy was identified more frequently in grade 3 than in grades 1 and 2 neoplasms (p = 0.001). Additionally, grade 3 neoplasms occurred more often with invasive (stages T2 to T3) compared to superficial (stages TA, TIS and T1) tumors (p = 0.002). However, deoxyribonucleic acid ploidy was not significantly associated with tumor stage. Among the 49 patients treated by a definitive operation the median survival free of disease and median over-all survival were 33.7 and more than 120 months, respectively. Variables examined included deoxyribonucleic acid ploidy, tumor grade, tumor stage, primary tumor site and type of operation. In the univariate analysis deoxyribonucleic acid ploidy was the only significant predictor of survival free of disease (p = 0.04). Aneuploid tumors had a median survival free of disease of 19 versus 59 months for diploid tumors. However, in the multivariate analysis of factors affecting survival free of disease, the type of operation performed was the only significant variable. Patients undergoing nephroureterectomy with en bloc bladder cuff excision had a favorable survival free of disease (p = 0.04). Tumor stage was the only significant factor associated with over-all survival in univariate and multivariate analyses (p = 0.02 and 0.005, respectively). Patients with superficial tumors had a median survival of more than 120 versus 72 months for patients with invasive tumors. The data suggest that deoxyribonucleic acid ploidy may be a useful parameter to identify risk groups and plan the management of patients with primary transitional cell carcinoma of the upper urinary tract.

Carcinoma, Transitional Cell↗

The effect of thyroid hormone status on plasma glucose-insulin interrelationship in broiler chickens.

The aim of the present experiments was to study the plasma glucose-insulin relationship in eu-, hypo- or hyperthyroid broiler chickens. None of the thyroid states modified the fasting plasma glucose and insulin levels. Hypothyroid chickens exhibited a normal glucose tolerance and a normal glucose-induced insulin release after oral glucose (2 g/kg body weight) administration compared to euthyroid chickens. In contrast, hyperthyroid chickens exhibited an improved glucose tolerance accompanied by a lower insulin release. Insulin injections at a concentration of 0.1 U/kg body weight was only hypoglycemic in hyperthyroid chickens, which confirms the observation that these chickens are more sensitive to insulin. From this study it can be suggested that alterations in body composition according to thyroid status are at least partly mediated by changes in the control of carbohydrate metabolism by pancreatic hormones.

Animals↗

Pefloxacin: safety in man.

Pefloxacin has been in clinical use in France since 1985. During this period of time, the Rhone-Poulenc Drug Safety Department has received 213 spontaneous reports concerning patients who experienced a total of 316 adverse events. The level of such spontaneous reporting from physicians depends upon the frequency and the clinical significance of the events. Skin, musculoskeletal and CNS problems were the events most frequently reported. Thrombocytopenia was the most frequently reported laboratory abnormality, use of heparin being associated with this in many cases. From these data, pefloxacin in routine clinical use appears to be well tolerated. For the agent to be used in children in the future, its safety in this population should first be carefully investigated. At present it is contraindicated in children under 15 years of age.

Central Nervous System Diseases↗

Interferon-gamma-induced priming for secretion of superoxide anion and tumor necrosis factor-alpha declines in macrophages from aged rats.

Macrophage responses to recombinant IFN-gamma decline during aging, as measured by two criteria of macrophage activation, O2- and TNF-alpha secretion. The production of O2- by macrophages in response to opsonized-zymosan and recombinant rat IFN-gamma is 75% lower in 23-month-old rats than in 3-month-old rats. Furthermore, the secretion of TNF-alpha in response to IFN-gamma and LPS is almost absent in macrophages from aged rats. Production of both O2- and TNF-alpha by resident peritoneal macrophages from specific pathogen-free aged rats in response to priming and triggering stimuli was partially or fully restored by implantation of syngeneic pituitary grafts from young rats. These data demonstrate that macrophages from aged rats are defective in their response to a priming signal induced by IFN-gamma, and they suggest that impaired macrophage responses during aging may be reversible.

Aging↗

Low calcium diet in idiopathic urolithiasis: a risk factor for osteopenia as great as in primary hyperparathyroidism.

The bone mineral content of the radius was measured in 32 male renal stone formers, 18 of them presenting with idiopathic urolithiasis and 14 with primary hyperparathyroidism, a disease known to disturb bone metabolism. The idiopathic stone formers had been on regular treatment with a low calcium diet. The bone mineral content of the radius was reduced to a similar level in both groups of patients. The data suggest that idiopathic stone formers on a low calcium diet are at risk of osteopenia; the factors which could lead to a negative calcium balance included uncompensated renal hypercalciuria, hypophosphataemia and exaggerated serum levels of 1,25-dihydroxyvitamin D. To treat idiopathic hypercalciuria, thiazide diuretics, which reduce the renal excretion of calcium and have been shown to be beneficial for bone, seem safer than a low calcium diet.

Adult↗

Longitudinal survey in an endemic region of plasma soluble interleukin-2 receptor and antibody levels in Plasmodium falciparum malaria.

A survey involving 81 individuals living in Dafinso and Vallée du Kou no. 4 (near Bobo-Dioulasso), Burkina Faso, was performed in June 1987, August to September 1987, and January 1988, respectively, at the beginning of, during, and after the transmission season of malaria. The clinical longitudinal study during the transmission period allowed us to define three different groups in terms of both age and occurrence of malaria attack (5,000 Plasmodium falciparum per mm3 of blood and axillary fever of greater than 37.7 degrees C) as follows: group 1, persons less than or equal to 15 years old who had at least one malaria attack during the transmission period; group 2, individuals less than or equal to 15 years old who did not have any malaria attacks; and group 3, individuals considered to be protected (adults greater than 15 years old with no malaria attacks). Soluble interleukin-2 receptor (sIL-2R) levels were found to be significantly increased (P less than 0.001) in the first two groups (1,047 +/- 481 U/ml [mean +/- standard deviation]) as compared with the adult group (605 +/- 307 U/ml). Considering all the groups, no significant difference was observed between observation periods. Levels of sIL-2R were inversely correlated (r = -0.39, n = 237, P less than 0.01) with age (range, 4 to 67 years). Negative correlations were also noticed between the levels of sIL-2R and those of antibodies to somatic antigen of P. falciparum (immunoglobulin G [IgG] class [r = -0.33, n = 237, P less than 0.01] and IgM class [r = -0.20, n = 237, P less than 0.05]). IgG antibody levels to somatic antigen were correlated with age, but IgM antibody levels to somatic antigen were not. The possible role played by sIL-2R in effector mechanisms against malaria is discussed.

Adolescent↗

Impaired insulin action but normal insulin receptor activity in diabetic rat liver: effect of vanadate.

In vivo insulin resistance is a characteristic of the liver and peripheral tissues in 10-wk-old female rats with non-insulin-dependent diabetes induced by streptozotocin given on day 5 after birth. Oral administration of vanadate (0.2 mg/ml) for 20 days in the diabetic rats lowered their plasma glucose levels to normal values without affecting their basal plasma insulin levels. In the basal state as well as after submaximal or maximal hyperinsulinemia (euglycemic clamp studies), peripheral glucose utilization and hepatic glucose production in vivo were normalized in the diabetic rats after the vanadate treatment. In wheat germ agglutinin purified receptors, 125I-labeled porcine insulin binding, basal and insulin-stimulated insulin receptor kinase activities for both the autophosphorylation of the beta-subunit and the phosphorylation of the artificial substrate poly (Glu-Tyr) 4:1, were found identical in diabetic and control rats, treated or not with vanadate. Liver phosphoenolpyruvate carboxykinase activity was significantly enhanced in untreated diabetic rats (P less than 0.01) as compared with control rats and returned to normal values after the 20-day vanadate treatment. Thus, in that model of non-insulin-dependent diabetes, 1) oral vanadate exerts a corrective insulin-like effect on impaired insulin action both at the level of liver and peripheral tissues, 2) impaired insulin action with no alteration of the insulin receptor tyrosine kinase is observed in the liver of untreated rats, and 3) corrective effect of vanadate on liver glucose metabolism is probably distal to the insulin receptor kinase activity.

Animals↗

Shock wave monotherapy of staghorn calculi.

From June 1987 to October 1988, 52 staghorn calculi were treated without anesthesia by shock wave lithotripsy with the second-generation lithotriptor, Lithostar Siemens. 36 calculi were evaluated. Multiple sessions (n = 1-6) were necessary according to the size of the stone. The mean hospital stay for complete treatment was 7 days. Double-J stenting was used in 45% of the patients with calculi of less than 40 mm and in 81% of the patients with calculi of greater than 40 mm. After 3 months, 50% of the patients with calculi of less than 40 mm were free of stones, as were 43% of the patients with calculi greater than 40 mm. After 9 months, the stone-free rate rose to 75%. At 3 months, the success rate (stone free or residual fragments of less than 4 mm) is 87.5% and rose to 92% at 9 months. Two severe complications were observed: one patient with acute infected hydronephrosis with sepsis and one with perirenal hematoma. Shock wave lithotripsy monotherapy of staghorn calculi is possible in multiple treatment sessions. Double-J stenting is mandatory in most of the cases but, even in this condition, anesthesia is not necessary.

Humans↗

Shockwave treatment of ureteric stones in situ with second-generation lithotriptor.

During a 17-month period we treated in situ 334 patients with ureteric stones with a second-generation electromagnetic lithotriptor. Anxiety and discomfort were relieved with diazepam and pethidine chloride only. Ureteral stenting was used in 8.1% of upper, 36.4% of mid- and 5.7% of lower ureteric stones. The retreatment rate was 15%, but no patient had more than 3 sessions. The success rate of the treatment at 3 months was 88% for upper, 65% for mid- and 83% for lower ureteric stones. Open surgery had to be performed in 5 cases and ureteroscopies in 6 cases.

Diazepam↗

Diagnosis of bromethalin toxicosis in the dog.

Dogs given a single oral dose of bromethalin at 6.25 mg/kg developed a toxic syndrome characterized by hyperexcitability, tremors, seizures, depression, and death within 15-63 hours after bromethalin administration. Gross lesions included mild cerebral edema (2/5) and mild pulmonary congestion (2/5). Histologic lesions included diffuse white matter spongiosis (5/5), mild microgliosis (3/5), optic nerve vacuolization (3/5), mild thickening of Bowman's capsule (2/5), and occasional splenic megakaryocytes (2/5). Ultramicroscopic examination of midbrain stem revealed occasional swollen axons, intramyelinic vacuolization, and myelin splitting at the intraperiod line. Bromethalin was detected in kidney, liver, fat, and brain tissues, using gas chromatography with electron capture detection. Photodegradation of extracted bromethalin may limit accurate quantification of tissue residues.

Adipose Tissue↗

Early prediction of fetal macrosomia in diabetes mellitus.

We studied 374 pregnant diabetic women to determine the value of various ultrasound parameters in the prediction of fetal macrosomia. The correlation between ultrasonographic signs and maternal glycaemia in the development of fetal macrosomia was also studied. Significant correlation was observed between the accurence of hydramnios and future macrosomia during the second-trimester (p less than 0.001). Serum fructosamine levels as an index of maternal glycaemia in patients of macrosomic fetuses were significantly higher throughout the pregnancy as compared with mothers of infants with normal birth weight (p less than 0.001). These data suggest: 1. The presence of hydramnios in the second trimester is a useful predictor of macrosomia in diabetic patients (specificity: 86%, negative predictive value: 88%). 2. Maternal diabetic control during pregnancy has a significant influence on fetal growth and contributes to the development of fetal macrosomia. 3. The lack of correlation between the frequency of hydramnios and fructosamine levels suggests that a mechanism other than carbohydrate metabolism also plays an important role in the development of fetal macrosomia.

Adolescent↗

Increased in-vivo insulin sensitivity but normal liver insulin receptor kinase activity in dwarf chickens.

The effects of the recessive and sex-linked dw gene on insulin sensitivity and liver insulin receptors were compared in normal (Dw-dw) and dwarf (dw-dw) brother or half-brother chickens. At 3.5 weeks of age, following an overnight fast, exogenous insulin (0-6.9 nmol/kg body weight) was slightly but significantly more hypoglycaemic in dwarf chickens. At 4 weeks of age, following an oral glucose load (2 g/kg), glucose tolerance was the same in both genotypes, whereas plasma insulin levels were greatly decreased in dwarf chickens. At 5 weeks of age, plasma concentrations of glucose and insulin were the same in both genotypes in the fasting state and decreased in the fed state in dwarf chickens. In liver membranes prepared from fasted chickens, insulin binding was increased in dwarf chickens, while the affinity of insulin receptors and the insulin-degrading activity of the membranes were the same in both genotypes. Following solubilization with Triton X-100, liver receptors were successively purified on lentil then wheat germ lectins. Autophosphorylation of the beta-subunit did not differ between either the genotype or the nutritional (fed or fasted) state. In the basal state (in the absence of insulin) the tyrosine kinase activity of the receptor towards artificial substrate poly(Glu, Tyr)4:1 was significantly decreased in dwarf chickens by fasting. However, the change in tyrosine kinase activity of the receptor in response to insulin was similar, irrespective of the genotype and the nutritional state.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

The effects of selected bulky substituents on the pulmonary toxicity of 3-furyl ketones in mice.

Preliminary studies examined the toxicity of a series of simple alkyl 3-furyl ketone congeners of perilla ketone, 1-(3-furyl)-4-methylpentan-1-one (1), in mice, but little was known about how aromatic or bulky side chains might affect toxicity. Therefore, 3-furylphenyl ketone (2) 3-furylphenethyl ketone (3) and 1-3-furyl-4, 4-dimethylpentan-1-one (4) were synthesized to examine this problem. The 48-h LD50 (i.p.) in Notre Dame Swiss mice for each analog was greater than that of the parent toxicant, perilla ketone (1, 30 +/- 5; 2, 173 +/- 4; 3, 150 +/- 11; 4, 79 +/- 5 mumol/kg). Absorption and distribution of these compounds should be similar based on their lipophilicities. Preliminary evidence suggested that the reduced toxicities of 2, 3 and 4 compared with 1 cannot be explained on the basis of 13C-NMR (electron density) characteristics. Instead, the reduced potency likely is the result of steric hindrance of bioactivation by the bulky side chain substituents and(or) alternative metabolism on the phenyl ring rather than the furan ring of 2 and 3.

Animals↗