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Biomedical subjects

M Donnadieu

Publications and source records attributed to M Donnadieu.

At least 55 records · Page 3Linked to original sources

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↗

Variations of serum testosterone estradiol binding globulin (TeBG) binding capacity in infants during the first year of life.

Serum TeBG binding capacity was measured in 8 cord blood samples, and in peripheral venous blood from 39 male and 31 female infants aged from 1 day to 1 year. In cord blood, TeBG binding capacities were low (1.27 +/- 0.3 microgram/100 ml) with no sex difference. In male infants, TeBG binding capacities increased progressively from birth to 3 months, before decreasing to reach the normal prepubertal level at 6 months. Individual values ranged between 1.16 and 14.5 microgram/100 ml and were significantly correlated with plasma testosterone (r = 0.671, 95% confidence limits 0.440 to 0.818, p less than 0.005) and estradiol (r = 0.734, 95% confidence limits 0.121 to 0.942, p less than 0.01) levels. In female infants, individual values ranged between 1.17 and 14.5 microgram/100 ml, without correlation with age or plasma estradiol level. In male infants the data suggest a positive control ot TeGB binding capacity by estrogens, the negative effect of testosterone being delayed until after the 3rd month of age. In girls, the lack of correlation between TeBG and estradiol can probably be explained by rapid variations of plasma estradiol levels.

Age Factors↗

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↗

[Secretion of a beta lipotropine type substances by a corticomelanotropic adenoma in Nelson's syndrome (author's transl)].

Using radioimmunoassay of human melanotropic hormone (beta-MSH), were studied in one female patient with Nelson's syndrome the properties of the immunoreactive beta-MSH (beta-MSH-IR) secreted in the circulation in vitro by a pituitary adenoma. With Sephadex G-50 gel, beta-MSH-IR of plasma or from a culture mediium is eluted in greater part in a volume corresponding to a molecular weight of some 6,000 to 10,000. In the radioimmunological systems employed, the dilution curve of beta-MSH-IR in a culture medium is not parallel to that of synthetic human beta-MSH; by contrast, it is parallel to that a lipotropine, purified human beta-LPH.

Adenoma↗

Serum somatomedin activity depressed after glucagon administration in man.

The variations in serum somatomedin (SM) activity were compared in 14 subjects after glucagon injection (1 mg im), and in 10 controls. A significant decrease in SM activity was observed 30 and 60 min after glucagon (p less than 0.01 to less than 0.001) whereas no significant change was noted in the controls. Analysis of the dose-response curves suggests that this decrease reflects depressed SM concentration. No correlation was found between the variations of growth hormone (GH), cortisol, or fatty acids and those of SM activity. The maximum variations in glycemia, insulin and SM activity occured during the same time interval. These results suggest that glucagon may play some role in the regulation of circulating SM.

Child↗

Dynamics and characterization of plasma immunoreactive beta-melanocyte stimulating hormone in hemodialysis patients: its relationship to ACTH.

We studied the plasma immunoreactive beta-MSH ("beta-MSH") in hemodialysis patients to determine its basal level, plasma disappearance rate, gel filtration and immunological characteristics. All patients had increased plasma "beta-MSH" (90--440 pg/ml; normal less than 90 pg/ml). Plasma ACTH and cortisol values were within the normal range. Cortisol infusion over 2 h induced almost no plasma "beta-MSH" variation as compared to controls where "beta-MSH" decreased rapidly (apparent half-life 90 min.); more prolonged administration of corticosteroids (dexamethasone 0.5 mg every 6 h for two days) caused a slight (20%) but significant (P less than 0.001) decrease of "beta-MSH." On Sephadex G-50 endogenous "beta-MSH" eluted in a molecular weight range of 6,000--10,000. In our radioimmunoassay dilution curves of endogenous "beta-MSH" paralleled that of synthetic human beta-MSH, but not that of purified human beta-LPH. In conclusion, hemodialysis patients show a clear dissociation between elevated "beta-MSH" and normal ACTH plasma levels. "beta-MSH" probably has a decreased plasma disappearance rate and seems related to a substance different from human beta-MSH.

Adrenocorticotropic Hormone↗

[Demonstration of specific serum IgG with an "in vitro" radioimmunoassay (RAST IgG) (author's transl)].

By using discs coated with allergens (RAST, Pharmacia) anti-human gammaglobulin goat antibodies, we could demonstrate specific IgG on sera whose IgE had been destroyed by heating at 56 degrees C for 4 hours. A detailed protocol is given. Preliminary results demonstrate absence of specific IgG in untreated patients with pollen allergy, and conversely presence of these IgG in patients treated with immunotherapy against pollens; most patients with epithelia, food and/or mould allergies had specific IgG prior to immunotherapy.

Desensitization, Immunologic↗

Synthetic MIF has no effect on beta-MSH and ACTH hypersecretion in Nelson's syndrome.

The effect of synthetic MIF (H-Pro-Leu-Gly-NH2) on beta-MSH secretion was studied in five patients with Nelson's syndrome and in one patient with Addison's disease. Two milligrams of the tripetide were injected intravenously (1 mg in an acute injection, followed by a 30-minute-infusion of 1 mg in 20 ml of saline solution). No consistent effect could be observed during the 90-minute period after the beginning of the infusion. In the same patients, LVP stimulation and dexamethasone suppression tests brought about significant changes in the plasma beta-MSH and ACTH levels.

Addison Disease↗

The liver as a source of somatomedin.

Somatomedin (Sm) activity (measured by [35S] utake in chick embryo cartilage) was determined in serum samples simultaneously drawn from the hepatic vein, portal vein, femoral artery and demoral vein of seventeen anaesthezied normal adult dogs). A pool of human serum was taken as reference (Sm = 1 U/ml). Sm levels in the peripheral vein of dogs were 0.38 +/- 0.03 U/ml). Mean +/- SEM). Sm activity was greater in the hepatic vein (0.48 U/ml) than in the other vessels (0.36, 0.39, 0.38 U/ml), and the paired differences were significant (P less than 0.002 to P less than 0.05). In three dogs which received b-GH (20 IU/day), the Sm levels were significantly increased after nine days in the femoural vein (P less than 0.05) and in the hepatic vein (P less than 0.05). The validity of the assay is discussed; a possible interference of NEFA in the assay is eliminated. The difference of Sm levels between hepatic and portal veins, related to hepatic flow measured in seven of these dogs, indicate an important production of Sm by the liver.

Animals↗

[Liberation of growth hormone and melanocyte-stimulating hormone in natural and melatonin-induced human sleep (author's transl)].

As in the early period of night sleep, plasma levels of human growth (HGH) are markedly elevated in afternoon sleep in healthy young males. Melatonin (50 mg i.v.) induces marked secretion of HGH when sleep is prevented. It decreases latencies for sleep onset and deep sleep significantly, and markedly enhances peak secretion of HGH during slow-wave sleep. Plasma melanocyte-stimulating hormone (betal-MSH) levels were influenced neither by melatonin nor by sleep.

Growth Hormone↗

Organ culture of human somatotrophic pituitary adenomas: ultrastructure and growth hormone production.

Ten somatotrophic adenomas removed from acromegalic patients and fragments of the non-tumoural surrounding pituitary were submitted to organ culture for periods of up to one month. Electron microscopic observation shows that these tumours retain their histological differentiation throughout the culture period. The cell morphology of the cultured tumours remains essentially unchanged and in particular the secretory granules keep their initial size (150 and 130 nm). However, the granules disappear gradually so that most of the cells look chromophobic by the 4th week of culture, and numerous lysosomes as well as autophagic figures appear at the same time. The hGH concentration in the culture medium has been measured of 4 adenomas. It is very high (10-fold greater than that from non-tumoural pituitary medium) during the first week (range 200-300 mug/ml). It still remains very high in the same experiments until the second week of culture in one experiment (200 mug/ml). After incubation of cultures with 3-H-leucine 3 H-hGH is obtained in the medium giving evidence of hormone synthesis by adenoma cells in culture. 3-H-hGH represents 40 percent of 3-H-proteins in the culture medium and gives the same elution pattern as standard hGH on Sephadex G 100 chromatography. A certain degree of correlation is observed between morphological and biological results: the greatest hGH production is obtained from explants which maintain the best histological appearance.

Acromegaly↗

[Heterogeneity of human growth hormone in cultures of pituitary adenomas].

Human growth hormone obtained from cell culture of pituitary adenomas cannot be distinguished from hormone extracted from normal pituitaries as far as the physical, chemical and immunologic characteristics are concerned. From a quantitative point of view the proportion of high molecular weight forms seems greater in the case of the extracted hormone and the intra-cellular hormone than in the case of the hormone secreted in the culture medium. From the biological point of view the hormone obtained from the culture medium seems more active "in vivo" than the extracted hormone. The preliminary results of a compartimental kinetic study suggest a system of two pools of growth hormone with different rates of use.

Adenoma↗