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Biomedical subjects

M Binoux

Publications and source records attributed to M Binoux.

At least 91 records · Page 5Linked to original sources
PubMed1986

Specific assay for insulin-like growth factor (IGF) II using the IGF binding proteins extracted from human cerebrospinal fluid.

A protein-binding assay for insulin-like growth factor II (IGF II) is described. The assay uses IGF binding proteins extracted from human cerebrospinal fluid which have selective affinity for IGF II. IGF I was 9 times less potent than IGF II in displacing [125I]IGF II, and when mixtures of the IGFs were assayed at IGF I/IGF II ratios of 2, 5, and 10, interference from IGF I in the assay was 0%, 5%, and 9%, respectively. Given the serum concentrations of IGF I and IGF II estimated by RIA and by this protein-binding assay, IGF I can be said to have had no cross-reaction when IGF II was assayed in human serum and at most 5% cross-reaction in the case of rat serum. After separation of IGFs from their binding proteins by acidic gel filtration, serum IGF II levels (mean +/- SE) measured by this method were 1322 +/- 66 ng/ml in normal adults, 500 +/- 65 ng/ml in patients with total GH deficiency, 1327 +/- 69 ng/ml in untreated acromegalic patients, and 1817 +/- 145 ng/ml in uremic patients undergoing chronic hemodialysis. In postpubertal young rats, the mean serum IGF II level was 43 +/- 2.6 ng/ml and after hypophysectomy it was 16 +/- 2.4 ng/ml. Although the IGF II levels in man and in the rat were different, they appeared to be similarly GH dependent, although less so than IGF I. In view of the sensitivity (0.03 ng IGF II) and the specificity of this assay, the small quantities of cerebrospinal fluid required (1 mu leq/assay tube) and its applicability for IGF II measurement in several species, the use of this assay for measuring IGF II in a variety of biological media can be envisaged.

Adolescent↗
PubMed1986

Serum levels of insulin-like growth factor (IGF) and IGF-binding protein in constitutionally short children and adolescents.

Serum insulin-like growth factor (IGF) and IGF-binding protein (IGF-bp) levels were studied in 92 constitutionally short children and adolescents (height less than mean for age -2 SD) and in 13 subjects after completion of growth. IGF levels increased with age in a manner similar to that in normal subjects, but at lower levels (P less than 0.001). The values were 0.41 +/- 0.03 SEM U/ml in 1 to 5 year old children, 0.72 +/- 0.03 U/ml in 6- to 16 year old prepubescent children and 0.95 +/- 0.05 U/ml during puberty. IGF-bp levels developed in a similar way, the values being 0.45 +/- 0.06, 0.61 +/- 0.04 and 0.85 +/- 0.06 U/ml, respectively, for the three periods considered. Both IGF and IGF-bp levels in each of the three groups were significantly lower than those in normal subjects at the same stage of development. After fusion of the epiphyses, IGF and IGF-bp levels were within the normal range. A longitudinal study was undertaken in 15 subjects, showing increases in height corresponding with increases in IGF levels. For all the subjects studied during their growth period, there was a correlation between height age and IGF levels (r = 0.64, P less than 0.001). All the subjects exhibited a normal rise in GH levels following stimulation. Although the possibility of quantitative or qualitative disorders of GH biosynthesis cannot be excluded in some of the cases, our data are compatible with the hypothesis that the growth retardation observed in constitutionally short children results, at least in part, from insufficient IGF production during post-natal growth.

Adolescent↗
PubMed1985

Triiodothyronine stimulates the production of insulin-like growth factor (IGF) by fetal hypothalamus cells cultured in serum-free medium.

Grown in serum-free medium, dissociated cells from fetal mouse hypothalami release insulin-like growth factors (IGFs) and their binding proteins (IGF BPs) into the culture medium. Addition of triiodothyronine (10-12-10-8 M), which enhances neuron maturation, resulted in a significant increase in IGF concentration. By contrast, there was no significant effect on IGF BP. These results suggest a role for thyroid hormone in the control of IGF biosynthesis in nerve cells.

Animals↗
PubMed1985

Serum levels of insulin-like growth factor (IGF) and IGF binding protein in insulin-dependent diabetics during an episode of severe metabolic decompensation and the recovery phase.

Serum insulin-like growth factor (IGF) and IGF-binding protein (IGF BP) levels were determined in 13 insulin-dependent diabetic patients (30-60 yr of age) during an episode of severe metabolic decompensation and the recovery phase. After separation by acidic gel filtration, the samples were assayed for IGF using a protein-binding assay (which measures mainly IGF I-related peptides) and for IGF BP by measuring the binding activity, in both assays using IGF I as tracer. The reference standard was a pool of normal adult serum with an assigned potency of 1 U IGF and 1 U IGF BP per ml. The mean IGF level in the uncontrolled state, 0.55 +/- 0.05 (SEM) U/ml, was about half that of normal subjects (1.03 +/- 0.03 U/ml, P less than 0.001). With treatment, IGF levels reached the normal range within 3 days. The pattern of changes in IGF BP levels was roughly similar, although the values in the uncontrolled state were less depressed (0.78 +/- 0.04 U/ml vs. 0.98 +/- 0.04 in normal subjects, P less than 0.01). Highly significant correlations (P less than 0.001) were found between IGF levels and the biological parameters reflecting control of the diabetes: glycosuria (r = -0.60), glycemia (r = -0.52), ketonemia (r = -0.65), and HCO3- (r = 0.58). Similar but less significant correlations were found for IGF BP. The mean GH level during the period of metabolic decompensation (9.0 +/- 1.5 ng/ml) was elevated compared to that after recovery (2.9 +/- 0.8 ng/ml) (P less than 0.025). There was a negative correlation between GH values and IGF levels (r = -0.67, P less than 0.001). The correlation with IGF BP was much less significant (r = -0.38, P less than 0.05). The results clearly reflect the role of insulin and nutritional factors in the control of IGF levels. They also support the notion that the biosynthesis of IGF and IGF BP is not regulated in the same way.

Adult↗
PubMed1984

Preferential measurement of insulin-like growth factor (IGF) I-related peptides in serum with the aid of IGF-binding proteins (IGF BPs) produced by rat liver in culture. Estimation of serum IGF BP levels.

A protein-binding assay for insulin-like growth factor (IGF) was developed which preferentially measures IGF I-related peptides in serum. Binding proteins (BPs) extracted from the culture media of livers from approximately 4-week-old rats were used in the assay, with pure IGF I as tracer and a partially purified IGF preparation as standard. Serum samples were gel filtered in acetic acid to separate the IGFs from their BPs. IGFs could be detected with this assay in extracts corresponding to as little as 0.2 microliter normal serum. The affinity of these liver BPs was greatest for IGF I. IGF II, somatomedin A, and multiplication-stimulating activity were found to be 2, 3, and 10 times less potent, respectively, than IGF I in displacing [125I]IGF I. There was no cross-reaction with insulin and proinsulin, structurally the most closely related peptides. There was a highly significant correlation (r = 0.98, P less than 0.001) between IGF values obtained from simultaneous assays, using either 1) somatomedin C/IGF I antibodies, or 2) the liver BPs, for acromegalic, normal, and hypopituitary serum extracts. Nevertheless, the protein-binding assay yielded values 1.7-fold those of the RIA. The BPs therefore do not possess the specificity of the antibodies for IGF I, but they do have the advantage of being less species specific in that they permit measurement of IGFs in the rat (among others) with the same sensitivity as in man. The validity of the assay was demonstrated both by the studies of IGF levels as a function of age, which yielded a profile characteristic of IGF I, and by the GH-dependence of the IGF levels measured. Mean IGF levels (+/- SEM) were the following: 1.03 +/- 0.03 U/ml in normal adults; 2.62 +/- 0.10 in acromegalic patients; 0.19 +/- 0.01 in patients with total GH deficiency; 0.58 +/- 0.04 in patients with partial GH deficiency (the reference serum being assigned a potency of 1 U IGF/ml). Human GH administration (6 mg/m2, im) to untreated hypopituitary patients on average provoked a 2-fold increase in IGF levels within 24 h. In hypophysectomized rats there was a close relation between the IGF level attained and the dose of GH administered (P less than 0.001). IGF BPs were titrated by incubating different concentrations of the serum extracts with [125I]IGF I and comparing these with a BP preparation obtained from the reference serum used in the IGF assay and arbitrarily assigned a value of 1 U IGF BP/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1984

Serum levels of insulin-like growth factor (IGF) and IGF binding protein in constitutionally tall children and adolescents.

Serum insulin-like growth factor (IGF) and IGF binding protein (BP) levels were studied in 89 constitutionally tall children and adolescents (height greater than mean for age + 3 SD in 90% of the subjects). After separation by acidic gel filtration, the samples were assayed for IGF using a protein-binding assay (which measures mainly IGF I-related peptides) and for IGF BP by titration, in both cases using IGF I as tracer. The reference standard was a pool of normal adult serum with an assigned potency of 1 U IGF and 1 U IGF BP/ml. IGF levels increased with age in a manner similar to that in normal subjects, but at higher concentrations (P less than 0.02). The values were 0.77 +/- 0.05 (SE) U/ml in 1- to 5-yr-old children, 0.96 +/- 0.08 U/ml in 5- to 11-yr-old prepubescent children and 1.51 +/- 0.07 U/ml during puberty. BP levels developed in a different way from the above in that the increase with age was slight (0.70 +/- 0.07, 0.67 +/- 0.09, and 0.97 +/- 0.07 U/ml, respectively, for the three periods considered) and the levels were lower than those of normal subjects (P less than 0.005). After fusion of the epiphyses both IGF and BP levels were within the range of normal values. Thirteen girls underwent prolonged treatment (mean, 26 months) with ethinyl estradiol (250-300 micrograms/day). Deceleration in growth was accompanied by a progressive decrease in IGF levels throughout the period of therapy and a rise in BP levels during the first 6 months, after which they stabilized within the range of normal values. Although it is possible that excessive secretion of GH (which was not demonstrated by the usual tests) may be the cause of the elevated IGF levels during growth in these constitutionally tall subjects, it seems likely that the high IGF levels combined with the abnormally low levels of BP were responsible for their excessive growth.

Adolescent↗
PubMed1982

Evidence for production by the liver of two IGF binding proteins with similar molecular weights but different affinities for IGF I and IGF II. Their relations with serum and cerebrospinal fluid IGF binding proteins.

Studies of the competitive binding of IGF I and IGF II and 125I-labelled IGF I and IGF II to the specific binding proteins (BPs) produced by the liver in culture suggest that two BPs exist, one with a selective affinity for IGF I and the other with a selective affinity for IGF II. The ratio of the former BP to the latter appeared to be higher in the culture medium of young rat livers and of fetal human livers than that in the culture medium of adult human livers. The two BPs form complexes with their IGFs with the same apparent molecular weight of approximately 40K. With gel filtration of adult human serum both types of BP eluted with the greater than 100K and the 40-70K molecular weight material. The BP with the selective affinity for IGF II predominated in the 40-70K material as well as in the cerebrospinal fluid of adult human subjects.

Adult↗
PubMed1980

Somatomedin production by rat liver in organ culture. II. Studies of cartilage sulphation inhibitors released by the liver and their separation from somatomedins.

Inhibitors of cartilage sulphation have been found to be released by the rat liver in organ culture. They cause a decrease in [35S]sulphate uptake by embryonic chick cartilage and, when added to a constant amount of serum, counteract the somatomedin (SM) activity of the serum. Both of these effects are dose-dependent. Their antagonistic action, investigated in the presence of increasing concentrations of serum, appeared to resemble non-competitive inhibition which would suggest different sites of action for SM and inhibitors. Incubation of the liver explants with cortisol (0.01-1 microgram/ml) increased the sulphation-inhibiting activity of the culture medium and the effect was dose-dependent. Simultaneous addition of cycloheximide suppressed the inhibition. Gel filtration of the culture medium on Sephadex G 75 showed that: a) at pH 7.9, inhibitors eluted in the same fractions as [125I]SM-A bound to its carrier (apparent molecular weight approximately 45 000); b) at pH 2.4, inhibitors still eluted as large molecules, but SM activity appeared in the same fractions as the dissociated [125I]SM-A. The question arises whether the cartilage sulphation inhibitor might not be the same molecule as the SM-carrier protein released by the liver.

Animals↗
PubMed1980

[Contribution of the IGF (insulin-like growth factors or somatomedins) competitive binding assay in the study of growth disorders in children (results for 124 observations) (author's transl)].

A competitive binding assay for IGF (insulin-like growth factors) employing a specific carrier protein produced by rat liver in culture has been used in a study of a variety of growth disorders in children. In 34 subjects with a total somatotropic deficiency, serum IGF levels were significantly (p < 0.001) lower than those in normal children for whom the means were 0.57 +/- 0.05 (SEM) U/ml between the ages of 1 and 5, and 1.01 +/- 0.11 U/ml between the ages of 5 and 15. Within this group of patients, there was also a significant difference in IGF levels depending on whether the deficiency was idiopathic (0.16 +/- 0.03 U/ml) or caused by a tumour (0.49 +/- 0.06 U/ml). IGF levels were particularly low in 2 cases of Laron's syndrome (0.08 and 0.03 U/ml) and 6 cases of coeliac disease (0.19-0.27 U/ml). In the later group, a gluten-free diet resulted in a rise in IGF levels. However, the stunted growth observed in 10 cases of Cushing's syndrome was found to be independent of IGF levels which fell within the normal range (1.02 +/- 0.11 U/ml). For 34 children investigated because of idiopathic retarded growth varying from --2 to --4 SD, the mean IGF levels (0.68 +/- 0.04 U/ml) were significantly lower than controls (p < 0.001). By contrast, abnormally high IGF levels were found in children with tall stature (> 3 SD). In 7 children aged between 1 and 5, the mean was 0.94 +/- 0.05 U/ml and in 17 older patients, 1.47 +/- 0.11 U/ml, with some cases reaching levels similar to those of untreated acromegalics. In both age groups the means were significantly higher than control levels (p < 0.001). Oestrogen treatment led to a progressive drop in IGF levels accompanied by slower growth, and normal levels were reached by the time ossification was established.

Adolescent↗
PubMed1979

Characterization of lipotropin-, corticotropin-, and beta-endorphin-immunoreactive materials secreted in vitro by a human pituitary adenoma responsible for a case of Nelson's syndrome.

A human pituitary adenoma responsible for a case of Nelson's syndrome was maintained in organ culture and the incubation medium was examined with four different RIAs; human corticotropin (ACTH), beta-MSH, lipotropin (LPH), and beta-endorphin (beta-End). All four immunoreactivites (IRs) were present in the medium obtained after 24 h of incubation. Gel exclusion chromatography under denaturing conditions (6 m guanidine HCl) revealed several immunoreactive components. Two components having both human beta-MSH (beta-hMSH) and human LPH (hLPH) IR coeluted with beta-hLPH and gamma-hLPH; a component with beta-hMSH IR but no hLPH IR coeluted with [125I]beta-hMSH; a component with human ACTH (hACTH) IR eluted at the position of hACTH. Sephadex G-50 gel exclusion chromatography revealed that approximately 80% and 20% of human beta-End (beta-hEnd) IR were accounted for by components coeluting with beta-hLPH and beta-hEnd, respectively. These data demonstrate the presence in this incubation medium of materials similar to if not identical with beta-hLPH, gamma-hLPH, hACTH, beta-hMSH, and beta-hEnd; they suggest that all of these peptides may be secreted in the circulation of patients with Nelson's syndrome.

Adenoma↗
PubMed1979

Immunoreactive beta-MSH in human plasma and in a corticotrophic adenoma culture medium. Its relation to the lipotrophins.

In order to characterize more accurately the relationship between immunoreactive beta-MSH ("BETA-MSH") and the lipotrophins (LPH) we attempted to investigate the gel filtration and the immunological characteristics of "beta-MSH" in the plasma of patients with Nelson's syndrome and Addison's disease as well as in the culture medium from a human corticotrophic adenoma using a sensitive radioimmunoassay from human beta-MSH. When added either to hormone free plasma or to a plasma from a patient with Nelson's syndrome all the human beta-MSH (hbeta-MSH) elutes from a Sephadex G-50 column as a single peak in a volume corresponding to its molecular weight. In contrast plasma "beta-MSH" in 3 patients with Nelson's syndrome and one patient with Addison's disease almost completely elutes in a volume corresponding to a molecular weight range of 6000-10 000; no "beta-MSH" can be detected in its normal elution volume. Drastic pH change (8.2 to 2.3) does not significantly alter the elution pattern. Chromatography of a corticotrophic adenoma culture medium gave a similar pattern of "beta-MSH" with a main peak in the molecular weight range of 6000-10 000. In our radioimmunoassay the culture medium and purified hbeta-LPH gave parallel displacement curves for [125I]hbeta-MSH. It is suggested that hbeta-LPH or a closely related substance is the main material responsible for "beta-MSH" immunoactivity.

Addison Disease↗
PubMed1978

Early paradoxical decrease in serum somatomedin activity following injection of growth hormone.

The early effects have been investigated of an intra-muscular growth hormone injection (6 mg/m2) on serum somatomedin activity in 21 children with growth hormone deficiency and in 5 children with constitutional short stature. In cases of hGH total deficiency, there was an early and significant decrease in SM activity, which reached a minimum level 2 hours after the injection (-34% p less than 0.01). After 24 hours, SM activity increased to +64% above basal levels. In cases of hGH partial deficiency and in short, non-hGH deficient children, no similar early changes were observed. Neither was any correlation found between the variations in SM activity and those in hGH or free fatty acid levels. The unexpected early decrease in SM activity following hGH administration seems to be related to GH deficiency.

Child↗