Biomedical subjects

G Milhaud

Publications and source records attributed to G Milhaud.

At least 55 records · Page 3Linked to original sources

PubMed1990

Hypoprolactinemic effect of calcitonin gene-related peptide in the rat.

The effect of calcitonin gene-related peptide (CGRP) on prolactin (PRL) secretion was studied in female rats. Prepubertal female rats were submitted to the stressful stimuli of injection, blood puncture and thermal stress. Lactating rats were exposed to suckling stimulus. The effects of CGRP on PRL release were compared to those of calcitonin (CT). CGRP i.p. or s.c. prevents the increase in circulating PRL induced by stress. This effect was observed two hrs and even 24 hrs after CGRP administration. It was elicited at all doses tested, 2.5, 1.25 and 0.6 micrograms per animal. The time course of the actions of CGRP and CT are different. It is proposed that CGRP and CT act on different receptors.

Aging↗

PubMed1990

The gill lipids of spawning Pacific salmon.

The gill phospholipids of 2 Pacific salmon species, Oncorhynchus keta and O gorbuscha, were composed of 38-43% phosphatidylcholine (PC) and 19-22% phosphatidylethanolamine (PE). Ether phosphoglycerides constituted 4-8% of the total PC fraction and 37-51% of the PE fraction. No significant changes in gill phospholipids were observed between those of pre-spawning fish in sea water and those of spawned salmon in the river. Cholesterol, however, was higher in the latter (0.59% vs 0.38%).

Animals↗

PubMed1990

Regulation of plasma calcium and phosphate in calcitonin-infused rats.

The effects of long-term constant infusion of moderate doses (2-32 ng/h) of salmon calcitonin (sCT) on plasma Ca (and its radionuclide 45Ca), Pi, Mg, and on endogenous rat CT (rCT) metabolism were investigated in the rat. Daily variations were included. 1) The plasma concentrations of Ca and Pi fell and that of Mg increased transiently during infusion, with the duration of responses (1-3 days) depending on the sCT dose. Rats infused with 8 ng/h sCT remained sensitive to CT after 7 and 14 days, as indicated by the effects of minipump removal and of a bolus injection of exogenous sCT on plasma mineral concentrations. 2) In contrast to control rats, the well-established daily variations in plasma Ca and Pi levels were no longer observed after 7 and 14 days of sCT infusion (8 ng/h), but normal variations persisted for plasma Mg, circulating rCT, rCT mRNA, and rCT thyroid content. 3) Statistical analysis of plasma mineral data, collected at five sequential times during days 7 and 14, showed that the means were not significantly different and that the daily variations were essentially identical on days 7 and 14 in control rats. In contrast, the variability of measurements for plasma Ca and Pi, but not for Mg, increased significantly between days 7 and 14 in infused rats, and the mean differences were significantly lower in infused rats on day 7 than in control rats. These results are consistent with a transitory loss of the daily variations for Ca and Pi (day 7) and the later (day 14) spontaneous recovery of some variations in these parameters, although the individuals remain unsynchronized.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Diagnosis of medullary carcinoma of the thyroid (MCT) by calcitonin assay using monoclonal antibodies: criteria for the pentagastrin stimulation test in hereditary MCT.

A new calcitonin (CT) immunoradiometric assay, using anti-11-7 and anti-24-32 CT fragment monoclonal antibodies was evaluated and compared to classical RIA. The sensitivity was 2.5 ng/L, the normal basal level (n = 83) was lower than 10 ng/L, the response to pentagastrin stimulation in control subjects was absent in nine and between 10-30 ng/L in nine others. (mean, 15.4). In patients with renal failure the basal level was increased between 10-52 ng/L. In patients with medullary thyroid carcinoma (MTC; n = 28), the basal level was between 189-28,900 ng/L. A pentagastrin test was performed as screening for familial MTC in eight patients with confirmed MTC at subsequent surgery; the calcitonin peak was equal or greater than 38 ng/L. Large differences exist between CT levels measured by RIA and immunoradiometric assay. The latter method provides a greater sensitivity to pentagastrin test and allows a better identification of microcarcinoma in hereditary cases of MTC.

Adolescent↗

PubMed1990

Fluoride pharmacokinetics in the ewe: a linear pharmacokinetics model.

The kinetics of fluoride was studied in a group of 3 adult ewes given sodium fluoride solutions at 3 dose levels (0.15, 0.375 and 0.75 mg/kg bw). Data were analysed using both compartmental and noncompartmental approaches. A 3-compartment open model was selected to describe the data. Comparison of the different parameters indicated an absence of change with dose level, suggesting that fluoride behaved linearly at the doses under study. The half-life of elimination was 2.57 +/- 1.28 h, the steady-state volume of distribution was 0.26 +/- 0.5 L/kg and the body clearance was 0.105 +/- 0.26 L/kg/h. It was concluded that a single intravascular fluoride administration (bolus) may be used to evaluate oral bioavailability of fluoride in sheep in toxicity studies.

Administration, Oral↗

PubMed1989

Loss of calcitonin receptors: a genetically transmitted defect in rats with high incidence of C-cell tumors.

C-cell tumors (medullary thyroid carcinoma) occur in humans and several other mammalian species. This tumor develops spontaneously with a high incidence (50%) in old Wag/Rij (Wistar-derived strain) rats. We have recently shown that calcitonin binding sites, which are present in the Wistar rats, are lost from renal medulla of the Wag/Rij rats before they reach the age of 1 month. In the present work, we investigated the distribution of calcitonin binding sites in the kidneys of first and second generation hybrids of Wistar x Wag/Rij rats. The absence of calcitonin binding sites from the renal medullas of 25% of F2 hybrids indicates that the deficiency is inherited in a Mendelian fashion and opens the way to establishing inbred strains lacking renal medullary calcitonin binding sites.

Aging↗

PubMed1989

Elevated levels of calcitonin mRNA: a marker for the spontaneous development of medullary thyroid carcinoma in rats.

The aging WAG/Rij rats (a Wistar derived strain) develop spontaneously medullary thyroid carcinoma with a high frequency (50%). We have studied calcitonin biosynthesis in Wistar and WAG/Rij rats strains in order to determine if early changes in this parameter occurred in the WAG/Rij strain. Thyroidal and plasma CT levels were measured in three months old WAG/Rij and Wistar rats before and after acute calcium challenge. Total RNA was extracted from thyroid glands and specific CT messenger RNA levels estimated by dot and Northern blot analysis with a 32P-labeled probe specific for CT mRNA. The capacity of mRNA to direct synthesis of CT precursor was also measured by translation in an in vitro system. Though mean basal circulating CT levels were equivalent in both strains, CT release after calcium stimulation was much increased in the WAG/Rij rat. CT content of the glands and CT mRNA levels were two fold higher in the WAG/Rij strain. Thus, in this strain, CT biosynthesis and secretion were increased long before the development of a C-cell carcinoma.

Animals↗

PubMed1989

[Detection and prognosis of medullary cancer of the thyroid gland. Influence of national multidisciplinary cooperation].

Medullary thyroid carcinoma is a rare and sometimes hereditary disease. The tumour can be diagnosed and followed up by measuring the amounts of calcitonin it secretes. The prognosis of this cancer largely depends on an early diagnosis and treatment. From the clinical and laboratory (calcitonin assays) data recorded in our department, we have endeavoured to determine the influence of a national multidisciplinary co-operative group (GETC: French medullary study group) on the diagnosis and prognosis of this malignancy. We are able to show that the number of medullary thyroid carcinomas detected (principally in their familial forms) has increased by 141 per cent after the GETC was created. Calcitonin levels at the time of diagnosis are significantly lower (P less than 0.05) in familial cases, which reflects an early detection. The same applies to post-operative calcitonin levels (P less than 0.005), so that in the long run a better prognosis can be expected. It seems therefore that together with a better knowledge of this cancer and its detection, the setting up of a national multidisciplinary co-operative group results in a better clinical and therapeutic approach of these patients, and particularly of the familial cases of medullary thyroid carcinoma.

Calcitonin↗

PubMed1989

Thyroglobulin, thyrotropin and thyrotropin binding inhibiting immunoglobulins assayed at the withdrawal of antithyroid drug therapy as predictors of relapse of Graves' disease within one year.

"Sensitive" thyrotropin (TSH), thyroglobulin (TG) and even thyrotropin binding inhibiting immunoglobulins (TBII) assays are now widely available. The objective of the present study was to determine the most accurate of these three parameters to predict the relapse of Graves' disease during the year following treatment discontinuation and to evaluate whether the assay of three markers is able to improve the prediction. TSH, TG and TBII were measured in the sera of 67 Graves' disease patients after at least 12 months of medical treatment. In 52 patients, TBII had also been determined before the beginning of the medical treatment. Under treatment, all the patients were clinically and biologically euthyroid, but in 9 goitrous patients it was impossible to lower the doses of carbimazole without an immediate relapse. The TSH levels of these 9 patients were still low in all cases but one; TG and TBII levels were abnormal in all. In the other 58 patients, the treatment was discontinued; 22 relapsed within one year, more frequently when a goiter was present. The most reliable parameter for the prediction of relapse was found to be TBII, as its specificity was high (94.5%), although its sensitivity was poor (45%); TG was more sensitive (64%) but far less specific (57%); TSH and "initial" TBII appeared to be of a little interest. When TBII was elevated prior to the withdrawal of treatment, the determination of TG was useful: abnormal values of both TBII and TG were always associated with a relapse. When TBII testing was negative, the relapse risk fell to 0.26, and to 0.08 when three criteria were matched: no goiter, negative TBII, normal TG.

Antibodies↗

PubMed1989

Distribution of renal calcitonin binding sites in mammalian and nonmammalian vertebrates.

Calcitonin (CT), the hypocalcemic hypophosphatemic hormone, is present in many vertebrate species. The principal target organs for CT are, in mammals, kidney and bone, and in fish, bone and gill. We have investigated the presence of renal calcitonin binding sites in a fish (Salmo gairdneri), two amphibians (Bufo bufo and Rana esculenta), two reptiles (Pseudemys scripta and Gekko gecko), and two birds (Gallus domesticus and Cothurnix japonica). We compared their distribution to a mammal, the rat (Wistar strain), using quantitative autoradiography methods. Moreover, CT binding sites were also characterized in the chicken kidney by a membrane assay. No renal 125I-sCT binding sites were detected in the fish, the amphibians, and the reptiles studied. In the rat, binding sites were present in the outer medulla and in the cortex. In the chicken and in the quail, scattered binding sites were also observed in the medulla and in the cortex, whose pattern seemed to follow the distribution of the glomeruli and/or the collecting tubules. Chicken kidney membranes were also purified by sucrose gradient centrifugation. Scatchard analysis of the binding data revealed the presence of one type of 125I-sCT binding site with an apparent dissociation constant of 4.3 nM and a number of sites of 73 fmol/mg/protein. The present results suggest that calcitonin renal receptors appeared late in evolution and thus that a regulation of renal function by calcitonin was only effective in birds.

Animals↗

PubMed1989

Oral immunization with a free peptide from cholera toxin: local protection and IgA production.

It is frequently of great benefit for good protection against pathogens to elicit a local immunization. For example the importance of antibacterial as well as antitoxin local secretory IgA, for protection against cholera, has been underlined in several studies. We have already reported that oral administration of the peptide corresponding to the 50-75 sequence of cholera toxin (CT) B subunit elicits serum antibodies neutralizing CT activity. In this study we demonstrate that IgA with specificity to CT are present in intestinal secretions of mice immunized orally with the P50-75 or P30-50 peptides of CT B subunit. In addition local protection is observed in the intestine of P50-75 orally immunized mice. These results point out the potential of synthetic peptides as immunogens at the mucosal level.

Administration, Oral↗

PubMed1989

Early calcitonin hypersecretion and C cell hyperplasia in rats with high incidence of C cell tumors (Wag/Rij).

Wag/Rij rats, a Wistar-derived strain, develop on aging a spontaneous medullary thyroid carcinoma which shows many morphological similarities to the human neoplasm. Using biochemical and histological methods, we studied calcitonin secretion and C cell distribution in young and adult Wag/Rij rats, to characterize possible modifications in calcitonin synthesis and secretion as compared to the original Wistar strain. During the period investigated, the mean basal circulating levels of calcitonin of both sexes were not significantly different between the two strains, although the Wag/Rij rats tended to have higher values. After a calcium challenge, the circulating calcitonin levels increased normally in the Wag/Rij strain as compared to Wistar rats of the same ages. Histological observations of their thyroids revealed a significant C cell hyperplasia, along with a weak immunostaining in some of the cells, due to a lack of secretory granules. Thus, in addition to the ability of developing C cell tumours on aging, the Wag/Rij strain is characterized by an early C cell hyperplasia leading to an increase of calcitonin secretion after a provocative secretion test.

Aging↗

PubMed1989

A physiological view of in vivo calcium dynamics: the regulation of a nonlinear self-organized system.

Our aim is neither to re-evaluate the term homeostasis, nor to summarize the conventional concepts in the field of calcium metabolism and its regulation, nor even to comment on their advantages and their limitations (excellent recent reviews have been published). This paper is rather a position article and references to the current literature will be made only if they contribute to a better understanding of our proposals; in contrast, emphasis will be placed on a literature which has, until now, remained unfamiliar to the field of calcium metabolism. The text is organized around three related features which are largely dictated by the characteristics of our recently published compartmental self-oscillatory model for rat calcium metabolism: (a) The circadian behavior associated with calcium dynamics in vivo may be viewed as a "key" temporal behavior for investigating the spatiotemporal organization of calcium metabolism in the normal rat. Within the bone, a large part of this circadian behavior should stem from the physico-chemical properties of the transformations of calcium-phosphate associations at the extracellular fluid (ECF)/mature bone interface; (b) an important part of the maintenance of a nearly constant plasma calcium concentration (homeostasis) results from interaction between nonlinear oscillators belonging to both calcium metabolism and calcium-regulating hormones. This implies that: firstly, calcium metabolism, like any biological system, is a complex dynamic system which has evolved over a long period and whose metabolic components--gut, kidney, bone--are organized as dynamic entities, adapted to periodic relationships with the external environment. The intrinsic nature of the circadian behavior of bone calcium efflux proposed here is a sufficient demonstration of this. Secondly, the existence of rhythmic variations in the main calcium regulating hormones, parathyroid hormone (PTH), calcitonin (CT) and vitamin D (VitD), are in agreement with this argument. As developed below, fascinating properties emerge from interaction between oscillators (hormones and target organs) which provide a new perspective on calcium regulation; and (c) one of the striking properties of the kind of nonlinear dynamic system required for this representation of calcium metabolism is that periodicity is only one of many temporal expressions. Thus, qualitative diversity in the temporal expression of calcium metabolism can be expected with varying experimental situations and different modes of temporal regulation of calcium metabolism might be physiologically effective, depending on the species studied.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

Actinomycin D inhibits the rapid increase in translatable calcitonin mRNA provoked by acute calcium stimulation.

Calcium, injected to rats, elicits a rapid increase in translatable calcitonin mRNA, by acting probably at the post-transcriptional level, as no change in calcitonin mRNA could be detected by hybridization assay. In this study we have measured calcitonin mRNA extracted from rats subjected or not to acute hypercalcemia and pretreated or not with actinomycin D. Calcitonin mRNA was quantified by its ability to direct the synthesis of calcitonin (CT) precursors in a cell free system and by hybridization to a 32P cDNA probe specific for CT mRNA. Actinomycin D, injected 5 hours before calcium administration, decreased the incorporation of 3H adenine in liver and thyroid, but did not inhibit the rise in plasma levels of calcium and CT (measured by radioimmunoassay). The antibiotic was able to inhibit the eightfold increase in translatable mRNA elicited by calcium administration in the control animals. Hybridizable CT mRNA levels were not modified by the treatments. Thus the increase in translatable CT mRNA after calcium stimulation is independent of CT secretion and is probably due to post-transcriptional modifications involving the expression of other gene(s).

Animals↗

PubMed1989

Circadian rhythms of calcitonin gene expression in the rat.

The daily changes in rat thyroid calcitonin and its specific mRNA concentrations, and the relationship between their dynamics and the plasma levels of calcitonin, calcium and phosphate over a 24-h period were investigated. The circulating calcitonin concentration rose during the daily dark period when plasma calcium and phosphate levels were minimal, indicating that plasma calcitonin rhythm cannot be generated directly by a linear effect of calcium on hormone secretion. Moreover, we established that the expression of the calcitonin gene also exhibited periodic dynamics observable at the pretranslational level: the gland content of hybridizable specific calcitonin RNA displayed daily rhythms; specific RNA levels peaked during the light period and were minimal during the first part of the dark period. Significant changes in thyroid calcitonin concentrations also occurred over a 24-h period. Statistical analyses which distinguished between variations over the 24-h period and residual variations were performed to test the relationships between the various parameters. The daily rhythms of hybridizable RNA, thyroid calcitonin and plasma minerals appeared to be in phase, while the plasma calcitonin concentration displayed variations out of phase with these rhythms. The implication of the correlations observed on the residual variations is discussed in comparison with the temporal relationship between the daily variations. The results fit the hypothesis that hormone production and secretion are self-oscillating processes. Plasma concentrations of calcium and phosphate might play a role in the synchronization of the calcitonin metabolism periodicity.

Actins↗

PubMed1989

Low thyrotropin (TSH) levels in goiter. Relationship with scintigraphic findings and other biological parameters.

Low TSH levels are frequently encountered in patients presenting with goiter. We assayed TSH in 599 goitrous patients who were referred to us for scintigraphy and ultrasonography. When TSH levels were low or when a hot nodule was discovered at scintigraphy, free T3, free T4 and sex hormone-binding globulin (SHBG) were also assayed. TSH levels were always low in overt hyperthyroidism with elevated free T3. TSH levels were also low in patients with normal free T3 and free T4 in circumstances leading to mild hyperthyroidism such as hot nodules that suppressed extranodular thyroid tissue uptake, toxic multinodular goiter, De Quervain thyroiditis and some patients on amiodarone treatment. Low TSH levels were also encountered in 29% of the clinically euthyroid patients presenting with a multinodular goiter with normal iodine uptake, no hot area and normal free T3 levels. In diffuse goiter, low TSH and normal free T3 levels were more frequently associated when iodine uptake was low, mainly due to subacute thyroiditis which can be clinically silent. Low TSH levels were rarely observed in patients with "simple" goiter or uninodular goiter without hot areas. SHBG, which was elevated in 94% of the Graves' disease patients tested, was normal in all but two patients with low TSH and normal free T3 levels. This assay appeared to be of little relevance in goiter. In addition to imaging techniques which are usually performed first, TSH should be systematically assayed in goiter, except in cases of solitary cold nodules. When low, the patient is at risk of developing overt hyperthyroidism. Conversely, when an isolated low TSH level is observed, scintigraphy should be performed.

Goiter↗

PubMed1989

[Parathyroid hormone and calcitonin receptors].

Parathyroid hormone and calcitonin are involved in the regulation of calcium metabolism via specific receptors in target organs principally bone and kidney. The pertinent findings in this rapidly evolving area of research are briefly summarized. The receptors for these two hormones have been extensively localised, the transduction of their signal studied, the structure and the proteins composing the receptors characterised by covalent linking and purified by affinity chromatography or specific immunoprecipitation. The sequence of the receptors will be established in a near future using genetic engineering.

Adenylyl Cyclases↗

PubMed1988

Calcium metabolism in the rat: a temporal self-organized model.

Based on consideration of rat plasma Ca and 45Ca concentrations, we analyze the circadian behavior of Ca metabolism of the rat as the temporal expression of a self-organized system. We present a self-oscillatory model M for rat Ca metabolism based on a compartmental formalism, which includes a second-order autocatalytic process. M describes the entire mass of Ca as made up of eight compartments and predicts a distinction between 1) the amount of Ca deposited in zones of rapid bone growth and reutilized during bone maturation and 2) the amount of Ca in mature bone subdivided into four compartments. Two of these compartments, largely self-oscillating, may represent Ca-P associations at bone liquid/solid interface and are subject to osteoblast-osteocyte control. The other two compartments can be thought of as made up of a large expanding pool of hydroxyapatite (HA) crystals, which are largely unavailable as such, and a small pool or more available HA crystals. Bone Ca influx and rhythmic efflux play a major role in the regulation of Ca in extracellular fluid but must be dissociated from bone accretion and resorption. Application to Ca deficiency was analyzed. Conceptual consequences of the connection of Ca metabolism to a self-regulated system are discussed.

Algorithms↗