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Biomedical subjects

A Bailly

Publications and source records attributed to A Bailly.

51 records · Page 3Linked to original sources

Long-term management of insulin-treated diabetic patients with continuous subcutaneous insulin infusion.

Ten ambulatory diabetics were submitted to continuous subcutaneous insulin infusion (CSII) for periods of 6-18 months. With the exception of a patient who demonstrated a subcutaneous abscess, local tolerance was good. One patient suffered a severe hypoglycemic attack during the first days of CSII. Among the other subjects, hypoglycemic reactions were rare. However, blood glucose values under 50 mg/dl were recorded as frequently as during the control period. There was a non significant increment in insulin requirements and weight increased in almost all patients. In comparison with prepump period, we observed at the end of the study a significant decrease of mean blood glucose (140 vs 203 mg %), of urinary glucose output (8 vs 21 g/24 hr) and of HbA1 levels (7.6 vs 9.6%). As a rule, the improvement of diabetes control was noted throughout the study period. Nevertheless, normoglycemia was rarely reached. Diabetes stability improved as evidenced by a decrease of the standard deviation of monthly blood glucose values and by a reduction of M and MAGE indexes. In spite of the better metabolic control, we did not observe an improvement of renal function while lipid values were slightly modified. Motor nerve conduction velocities increased in 6 patients and ocular fluoroangiographic records demonstrated a reduction of microaneurysms and/or microhemorrhagic dots. As a group, the patients were satisfied with CSII and 8 of them wished to continue indefinitely with this treatment.

Adult↗

Activated steroid-receptor complex. Comparison of assays using DNA-cellulose or homologous nuclei.

When soluble steroid-receptor complexes are exposed to DNA-cellulose only activated complexes bind. The specificity of the binding was shown by its dependence on the presence of hormone during activation. However, prolonged incubation of non-activated steroid-receptor complexes with DNA-cellulose led to a progressive activation of these complexes. When the same hepatic cytosol containing heat-activated [3H]triamcinolone acetonide-receptor complexes was titrated by high concentrations of nuclei or DNA-cellulose the former bound 75% of the complexes, the later only 40%. This decreased binding was due on the one hand to a lower initial interaction between DNA-cellulose and activated complexes than between nuclei and these complexes and on the other hand to increased losses during washes when DNA-cellulose was used. For these reasons nuclei and not DNA-cellulose should be used when accurate measurements of the concentration of activated complexes are required. When only comparative data are needed DNA-cellulose may, however, be employed.

Adrenalectomy↗

The usefulness of a rapid method for total fast hemoglobins determination in screening for diabetes control.

We have used a simple and rapid method for the determination of total fast hemoglobins (HbA1a+b+c) in 102 diabetics and 36 normal controls. The method was described by Kynoch and marketed by Isolab. It proved to be useful in screening for patients with inadequate metabolic control in whom as a rule, total fast Hb values were higher than 8.5%. Mean Hb A1a+b+c value was significantly higher in the group of diabetics in comparison with normals (9.9 +/- 0.2 versus 6.9 +/- 0.8%). The diabetic patients were separated into four groups according to predetermined criteria of recent metabolic control. Even the patients considered to have a very good diabetes control during the past eight weeks, had supranormal total fast Hb values (7.7 +/- 0.2%). In the patients with good, poor and bad diabetes control, mean total fast Hb levels were respectively 9.3 +/- 0.3, 10.1 +/- 0.3 and 12.5 +/- 0.4%. In normals, there was a positive correlation between individual fasting blood glucose and total fast Hb values and in diabetics, mean blood glucose values correlated with total fast Hb levels. Hb A1a+b+c determinations also correlated with triglyceride values. We could find no significant association between high total fast Hb levels (greater than 8.5%) and the prevalence of retinopathy.

Blood Glucose↗

Factors modifying equilibrium between activated and non-activated forms of steroid-receptor complexes.

Steroid-receptor complexes formed in concentrated cytosol at low temperature, low ionic strength and neutral pH are unable to bind to nuclei. Various procedures are known to promote their 'activation'. In the present work it is shown that an increase in temperature only enhances the rate of the reaction whereas no change in the equilibrium between activated and non-activated complexes is observed. On the contrary an increase in ionic strength or pH, as well as a removal of a low-molecular-weight inhibitor, not only accelerate the reaction but also increase the concentration of activated complexes at equilibrium. Using two steroids differing 3-fold in their affinity for the receptor, no difference was seen in the effect of the bound steroid on receptor activation. When combining various activation procedures it was observed that they acted independently of each other and additively. In all cases they retained their property of either modifying only the rate of the reaction or both its rate and equilibrium. Using changes in pH, it was also possible to induce shifts in the equilibrium between activated and non-activated complexes. After activation at pH 6.5, a first equilibrium was attained. When the pH was increased to 8 the equilibrium was displaced towards higher concentrations of activated complexes. A lowering of the pH resulted in a reversal of steroid-receptor complexes from the activated to the non-activated state. To clearly establish that this was not due to irreversible damage of the receptor, which would render it unable to bind to nuclei, it was shown that the complexes which had reverted to the non-activated state were still susceptible to activation. Regulatory events may thus exist which, for a given level of hormone and receptor, modulate the concentration of activated steroid-receptor complexes.

Adrenalectomy↗

A low molecular weight inhibitor of steroid receptor activation.

Dilution at 0 degrees of rat liver cytosol incubated with [3H]triamcinolone acetonide provoked an enhanced binding of steroid-receptor complexes to nuclei. The explanation of this phenomenon was found to be an "activation" of the complexes. Dilution acted by decreasing the concentration of a cytosol inhibitor. This reaction was irreversible at 0 degrees: once activated the complexes could not be reversed to the nonactivated state by the addition of inhibitor. The presence of hormone was necessary, since hormone-free receptor molecules could not be activated by dilution. Removal of the inhibitor did not lead to activation of all complexes: after 24 h a "plateau" was attained where 55 to 70% of the complexes were activated. The inhibitor was shown to be a low molecular weight molecule by dialysis, Sephadex G-25 chromatography, ammonium sulfate precipitation, and ultrafiltration. Thus [3H]triamcinolone acetonide-receptor complexes present in a cytosol from which the inhibitor had been removed by Sephadex G-25 chromatography became spontaneously activated at low ionic strength and at 0 degrees. The inhibitor is not a steroid (at least of usual polarity) since it cannot be extracted by methylene chloride or adsorbed by activated charcoal. It is thermostable (resists to 30 min at 100 degrees). Its removal by incubation with a cation exchange resin suggests that it may be positively charged, however it is not complexed by EDTA. This inhibitor must be distinguished from a previously described inhibitor of steroid-receptor complexes binding to nuclei. The latter compound has been shown in various systems to be responsible for an artifactual saturation of nuclear acceptor by steroid-receptor complexes. It inhibits the binding to nuclear acceptors of already activated complexes and is probably a macromolecule. It is thus different from the low molecular weight activation inhibitor described in the present paper.

Animals↗

Interaction of rat-liver glucocorticoid receptor with DNA.

The complex of [3H]dexamethasone and rat liver receptor binds to rat liver DNA. This interaction takes place only in the presence of hormone and is enhanced by 'activation'. No evidence of saturatability can be obtained with concentrations of steroid-receptor complexes corresponding to those observed physiologically in the intact liver cell. The binding is inhibited by high ionic strength and by millimolar concentrations of divalent cations. No species specificity has been observed: the complex binds equally well to prokaryotic and eukaryotic DNA'S. There was no difference between binding to native and denatured DNA. In comparable conditions twice as much [3H]dexamethasone-receptor complexes were bound by DNA than by rat liver nuclei. Thus, the interaction of steroid-receptor complexes with DNA probably does not correspond to the recognition of a few very specific sequences. It is however possible that this interaction is actually operating in vivo in the intact cell.

Animals↗

Pancreatic B-cell response to a test-meal in lean and obese diabetic patients: relation to metabolic control.

We have measured fasting C-peptide reactivity (CPR) as well as CPR responses to a test meal in 83 diabetic patients and 41 non diabetic controls. In comparison to controls, basal CPR was decreased in lean insulin-treated diabetics with stable or brittle diabetes and in obese patients with brittle diabetes. Lean and obese maturity-onset diabetics had increased CPR levels and so had obese insulin-treated patients. Nevertheless, the CPR response to the test meal was clearly inadequate in all diabetics. In control patients, there was a positive correlation between fasting blood glucose and CPR levels. On the contrary, lean diabetics demonstrated a negative correlation between these parameters. Hemoglobin A1 levels were negatively correlated to fasting CPR levels in lean diabetics, indicating the importance of residual B-cell function for diabetes control. These correlations were obscured in obese diabetics. In our patients, circulating insulin antibodies had apparently no deleterious effect on metabolic control.

Adult↗

Association of DNA-bound progesterone receptors.

Steroid hormone-receptor complexes regulate the transcription of specific genes. Recent studies of high-affinity interactions between the receptors and discrete regions of DNA, together with gene-transfer experiments, have led to the precise mapping of hormone regulatory elements. Nothing is known, however, about the mechanisms whereby DNA-bound receptors modulate gene transcription. At the start of transcription in prokaryotes two oligomeric molecules of several regulatory proteins must bind to two specific DNA sites and interact with one another to regulate the binding of RNA polymerase to DNA. Using electron microscopy to observe progesterone receptor binding to regulatory regions of uteroglobin and mouse mammary tumour virus genes, we demonstrate a similar binding between receptor oligomers at two DNA sites. DNA loops are formed when the hormone regulatory elements are at a distance from one another. Thus, in common with certain prokaryotic systems, protein-protein interactions may be important in steroid hormone regulation of gene transcription.

DNA↗

Zinc deficiency and lymphocyte subpopulations. A study by flow cytometry.

Zinc deficiency is well known to alter immunity. We report the case of a 18-yr-old female with relapsing Crohn's disease who experienced acrodermatitis enteropathica due to zinc deficiency during total parenteral nutrition (TPN). Blood lymphocytes have been studied by flow cytometry: before zinc treatment an important decrease of T-helper lymphocytes with high level of OKM-5+ lymphocytes had been observed. Zinc-supplemented diet induced within a few days, a rise of T-helper lymphocytes and a proportional reduction of OKM5+ cells. Increased values of high metabolism surface marker (OKT-9) were also observed, as well as cytoplasmic modifications. The authors suggest that lymphocyte surface markers could be useful to monitor TPN in patients at high risk for zinc deficiency.

Acrodermatitis↗