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G Milhaud

Publications and source records attributed to G Milhaud.

At least 73 records · Page 4Linked to original sources

[The peroperative isotopic location of osteoid osteomas and other lesions exhibiting increased uptake on scintigraphy].

The technique, advantages and pitfalls of the isotopic localization and control during operation in orthopaedic surgery were evaluated throughout 28 interventions on lesions, which exhibited an increased uptake of a radioactive bone-seeker: the dimethyl-aminodiphosphonate, provisionally designated SF44 (Laboratoires Solabco, Coutras, France). For bone scanning, following the injection of this radiopharmaceutical that increased by 25% the lesion to normal bone ratio compared to the data for the diphosphonates in current use, the localization of lesions at surgical sites was carried out with the use of a sterilisable small radiation probe of a circular cross section 2 mm in diameter (Quartz et Silice, Paris, France). The probe was connected to a portable electronic device that converted the rates of radioactive disintegration into an acoustic signal, which increased with increasing radioactivity (Novelec, Meylan, France). The method was atraumatic and has proved to be useful at various times of the operation. More often, it was used to locate the lesion on the exposed bone. It enabled monitoring the progress of excisions and allowed to shorten their dimensions. The method was of great value at the end of the intervention for ensuring a complete excision as indicated by the lack of any residual focus of increased uptake detectable on the periphery of the operative site. Isotopic control during an operation is fully efficient to locate osteoid osteomas and other circumscribed lesions of the skeleton that give rise to an increased uptake of radioactivity.

Adolescent↗

Sequence and expression of the chicken calcitonin gene.

The avian calcitonin gene was isolated and sequenced; two mRNAs are expressed by tissue-specific alternate splicing. The peptides encoded by the mRNAs are the protein precursors of either calcitonin or calcitonin gene-related peptide (CGRP). Calcitonin is expressed predominantly in ultimobranchial bodies and CGRP in brain.

Amino Acid Sequence↗

Early spontaneous deficiency of calcitonin renal binding sites in rats with a high incidence of calcitonin-secreting tumors (WAG/Rij).

Old rats of the WAG/Rij strain have a high incidence (50%) of medullary thyroid carcinoma, a calcitonin (CT)-secreting tumor. We have characterized and quantified the topographical distribution of [125I]salmon calcitonin (sCT) binding sites in the kidneys of this strain, as compared to Wistar CF rats (2% incidence of spontaneous medullary thyroid carcinoma). We report here that, up to 15 days of postnatal development, the distribution of CT-binding sites in the kidney of the WAG/Rij strain was quite similar to that found in developing and adult Wistar CF rats. However, from the age of 1 month, sCT-binding sites were dramatically reduced in both the medulla and the inner part of the kidney cortex, though plasma CT levels were not significantly different in both strains. Adult WAG/Rij rats bearing a transplanted tumor for 12 weeks had a high level of plasma calcitonin and exhibited an even greater reduction of both medullary and cortical sCT-binding sites. These results suggest that the modification in the CT-binding sites in WAG/Rij rats is not a consequence of a possible down regulation due to elevated circulating hormonal level but could be inherited and possibly associated with the later development of the tumor in this strain.

Aging↗

Immunoreactive salmon calcitonin-like molecule in crustaceans: high concentrations in Nephrops norvegicus.

A salmon calcitonin (CT)-like peptide was characterized in various crustaceans by radioimmunological and radioreceptor assays. The highest levels of the molecule were found in the anterior part of the gut and the hepatopancreas of the Norway lobster: Nephrops norvegicus. Molecular sieving of this molecule suggested an apparent molecular weight of 4500 Da, that is higher than that of calcitonin. This peptide can be referred to as crustacean calcitonin as it inhibits the binding of labeled salmon CT to rat kidney membranes. The high concentration found in crustaceans suggested that this molecule could have an important role in this class of arthropods.

Animals↗

Calcitonin induces hypercalcemia in grey mullet and immature freshwater and sea-water adapted rainbow trout.

1. Changes in plasma calcium levels, in response to salmon calcitonin injections, were studied in freshwater and sea-water adapted trout (Salmo gairdnerii) and in grey mullet (Chelon labrosus). 2. Low doses (0.1 ng sCT/100 g body weight) elicited hypercalcemia in the two species studied. 3. High doses (0.5 microgram) provoked hypocalcemia only in freshwater and sea-water adapted trout. 4. An hypercalcemic response appears as the primordial effects of CT injections, higher doses of CT leading to hypocalcemic effects.

Acclimatization↗

Effect of calcitonin on the prolactin surge of proestrus.

The effect of calcitonin (CT) on the prolactin (PRL) surge of proestrus in rats was investigated under normal and perturbed lighting conditions. Salmon calcitonin (SCT) was injected i.p. on diestrus 2 or on proestrus, plasma PRL levels were measured by radioimmunoassay. SCT had no effect on the PRL surge under normal lighting conditions but it induced a small drop in PRL level measured on proestrus morning, 3 hours after CT injection. Animals submitted to perturbed light conditions had higher PRL levels than those kept under normal lighting. These data would indicate that for the female rats on proestrus the sensitivity to stress due to injection and blood sampling may be modulated by changing the photoperiod. SCT injection under these conditions may facilitate this destabilization in PRL level.

Animals↗

Down-regulation of rat kidney calcitonin receptors by salmon calcitonin infusion evidenced by autoradiography.

In treating age-related osteoporosis and Paget disease of bone, it is of major importance to avoid an escape phenomenon that would reduce effectiveness of the treatment. The factors involved in the loss of therapeutic efficacy with administration of large pharmacological doses of the hormone require special consideration. Down-regulation of the hormone receptors could account for the escape phenomenon. Specific binding sites for salmon calcitonin (sCT) were characterized and localized by autoradiography on rat kidney sections incubated with 125I-labeled sCT. Autoradiograms demonstrated a heterogenous distribution of 125I-labeled sCT binding sites in the kidney, with high densities in both the superficial layer of the cortex and the outer medulla. Infusion of different doses of unlabeled sCT by means of Alzet minipumps for 7 days produced rapid changes in plasma calcium, phosphate, and magnesium levels, which were no longer observed after 2 or 6 days of treatment. Besides, infusion of high doses of sCT induced down-regulation of renal sCT binding sites located mainly in the medulla, where calcitonin (CT) has been shown to exert its physiological effects on water and ion reabsorption. These data suggest that the resistance to high doses of sCT often observed during long-term treatment of patients may be the consequence of not only bone-cell desensitization but also down-regulation of CT-sensitive kidney receptor sites.

Animals↗

Clinical value of thyrotropin binding inhibiting immunoglobulins (TBII) assay in hyperthyroidism.

More than 500 sera were assayed for TBII under routine conditions using "Trak" assay in order to evaluate the sensitivity, specificity and prognostic interest of this determination in hyperthyroidism. The sensitivity for the diagnosis of Graves' disease was 83.5%, better in ophthalmopathic patients (93%) than in non ophthalmopathic patients (75%). The specificity was 99.4% with only one false positive in a hypothyroid patient. TBII level significantly decreases with carbimazole treatment except in patients who remain hyperthyroid. Determination of TBII before stopping carbimazole treatment or after surgery has a prognostic significance as a positive value indicates a relapse in almost all cases. Conversely, a fall of TBII to normal levels with treatment is insufficient to assess recovery. High levels are frequently observed after radioiodine therapy but do not indicate a poor prognosis.

Carbimazole↗

Clinical significance of a low concentration of thyrotropin: five immunometric "kit" assays compared.

We compared results of five sensitive immunometric assays of serum thyrotropin (TSH) in controls and in different groups of patients with hyperthyroidism, untreated or treated; secondary hypothyroidism; nonthyroidal illness (NTI); or depression; or who were being treated with amiodarone. With most kits, measured TSH concentrations did not overlap between controls and hyperthyroid patients. In untreated secondary hypothyroidism TSH was not always undetectable. Patients with NTI and depression showed many low TSH values, and among these categories of patients, we observed large discrepancies among the kits. This lack of specificity at low concentration means that one cannot assess hyperthyroidism by TSH measurement alone, but it can be used as the first screening test. Similarly, TSH determination cannot be used alone in monitoring therapy (e.g., with carbimazole, thyroxin, amiodarone) to assess the presence of hyperthyroidism. Nonetheless, this assay plays a well-established role in hypothyroidism detection. Four of the five kits were found useful for clinical evaluation, the fifth less so.

Adenoma↗

Oral immunization with a synthetic peptide of cholera toxin B subunit. Obtention of neutralizing antibodies.

The ability of free synthetic fragments of the cholera toxin (CT), administered by parenteral or oral route, without adjuvant, to induce antibodies cross-reacting with CT was tested. Two peptides corresponding to the sequences 30-50 and 50-75 of the CT beta chain were selected and synthesized. Both free peptides, given intraperitoneally or orally, without adjuvant, elicited seric antibodies cross-reacting with CT. The anti-(P50-75) antibodies were able to neutralize the CT activity. Our results show that protection against a toxin at the systemic level can be obtained with a synthetic peptide even when administered by an oral route.

Administration, Oral↗

Isolation and partial characterization of the calcitonin gene in a lower vertebrate. Predicted structure of avian calcitonin gene-related peptide.

The gene coding for calcitonin was isolated and characterized in a non-mammalian vertebrate, chicken. Sequencing of the 3'-end of this gene revealed after the calcitonin coding exon, an intron followed by an exon coding for a calcitonin gene-related peptide, which displays significant amino acid sequence homology with mammalian CGRPs so far sequenced.

Amino Acid Sequence↗

Purification and characterization of calcitonin receptors in rat kidney membranes by covalent cross-linking techniques.

We have characterized the binding parameters of renal receptors (Scatchard analysis revealed the presence of two binding sites: site I, Ka1 = 1.29 X 10(9) M-1, number of binding sites = 9.9 X 10(6)/micrograms protein; site II, Ka2 = 0.93 X 10(8) M-1, number of binding sites = 4.27 X 10(8)/micrograms protein) and studied the effect of solubilization. The high-affinity sites are preserved during affinity chromatography and the process results in a 6080-fold purification of those sites. The lower-affinity sites are also preserved but the overall purification factor is about 40% lower than that obtained using molecular sieving. The purification of the renal calcitonin receptor by molecular sieving (Sephacryl S-200) is accompanied by total loss of the high-affinity site; however, the low-affinity site is enriched over 1642-fold. Binding parameters were obtained for the purified fractions. Synthetic salmon calcitonin was also bound to renal membranes using the bifunctional reagent disuccinimidyl suberate and photo-affinity cross-linking using hydroxysuccinimidyl azidobenzonate reagent. Cross-linked receptor eluted in the same volume as solubilized membranes specifically binding salmon calcitonin (S-200 chromatography). Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of purified fractions showed several protein bands with apparent molecular masses ranging from 18 000 Da to 100 000 Da in the presence or absence of a reducing agent (2-mercaptoethanol). Autoradiography of polyacrylamide gels of cross-linked calcitonin receptor showed only three protein bands specifically binding salmon calcitonin. Their molecular masses were 70 000 Da, 40 000 Da and 33 000 Da respectively. The 40 000-Da molecule represents a major band (47% total binding species). This suggests that these three proteins are the principal components of the calcitonin receptor and that S-S bonds are not involved in the assembly of the receptor subunits.

Animals↗

Characterization and quantitative topographical distribution of salmon calcitonin-binding sites in rat kidney sections.

Renal binding sites for labelled salmon calcitonin (sCT) were studied using cryostat sections and autoradiography. Increasing concentrations of unlabelled sCT inhibited 125I-sCT binding. 125I-sCT bound to a single site with a Kd of 2 nM and a number of sites of 220 fmol/mg protein. Mammalian calcitonins had low affinities and peptides unrelated to CT were devoid of any significant affinity for 125I-sCT receptors. Autoradiograms disclosed a high concentration of 125I-sCT receptors mainly located in the outer medulla and heterogeneously in the renal cortex. The distribution of specific binding sites is in agreement with the current concepts of renal action of calcitonin.

Animals↗

Uptake of 131I-MIBG by medullary carcinoma of thyroid in familial cases.

Medullary carcinoma of the thyroid (MCT) and pheochromocytoma are APUD tumors. MIBG (Meta Iodo Benzyl Guanidine) uptake by pheochromocytomas is now well known but very few cases of MIBG uptake in sporadic MCT have been described. We report here the two first cases of inherited MCT with MIBG uptake.

3-Iodobenzylguanidine↗

Granular and extra-granular forms of immunoreactive calcitonin in normal rat "C" cells.

The intracellular localization of the intermediate calcitonin-related peptides produced during calcitonin maturation (CT, 3.4 Kd) from the polyprotein precursor (15 Kd) has been studied by means of subcellular fractionation of normal adult rat thyroid using a continuous hypertonic Percoll gradient. A fraction B (Bottom), containing the secretory granules, was separated from a fraction T (Top) constituted of rough and smooth membranes devoid of granules. Immunoreactive calcitonin extracted from both fractions was heterogeneous when analysed by gel electrophoresis followed by radioimmunoassay. In fraction T, the immunoreactive molecules assayed were associated with the membranes. Their apparent molecular weights (lower than 18 Kd) were compatible with the intermediates predicted by the aminoacid sequence of the precursor. However the maturation was not complete, as indicated by the absence of the monomer. The smallest molecular weight detected (4-4.5 Kd) was compatible with a calcitonin-katacalcin uncleaved molecule. These data strongly suggest the occurrence of a cleavage separating the N-terminal part of the molecule during the pre-granular step of calcitonin secretory pathway. In the granular fraction, the monomer constituted the granular matrix, representing 65% of the total immunoreactivity. The remainder was associated with the granules membranes, consisting of the 4-4.5 Kd precursor and some 43 Kd material which has already been demonstrated by others to be covalent polymers of calcitonin [17]. It is thus concluded that a second cleavage could take place in the granules where the major immunoreactive form is the processed calcitonin, either as free monomer or as covalent polymers associated with the membrane of the granules.

Animals↗

The kinetics of intestinal calcium absorption in the rat: an analytical and model building study.

The experimental data obtained from in vivo single pass perfusion of duodenal, jejunal, and ileal intestinal segments of 33- and 50-day-old rats have been used to test a series of models for calcium absorption. Each model was checked for the statistical validity and goodness-of-fit with the experimental data. The model adopted for the duodenum and jejunum had two major components, one saturable and the other nonsaturable, and a minor secretory component. This model was not applicable to ileal calcium absorption. Here the secretory component appeared to be much more important, and the absorption parameters varied in such a manner as to suggest that this intestinal segment was capable of short term autoregulation of dietary calcium absorption.

Animals↗