PubMed HealthSearch

Biomedical subjects

C Calmettes

Publications and source records attributed to C Calmettes.

At least 19 recordsLinked to original sources

CCP II: a novel calcitonin carboxy terminal peptide is expressed in normal thyroid tissue.

We have recently identified in medullary thyroid carcinoma the existence of a second calcitonin messenger, generated by a splicing between the 3' coding region of exon 4 and exon 5 of Calc I gene. It differs from the first one in its 3' coding sequence and codes for a calcitonin precursor which generates the same N terminal peptide, calcitonin and a specific 21 amino acid carboxy terminal peptide differing from Katacalcin by its 8 last amino acids. We searched for the expression of this new messenger in normal human thyroid tissue by Northern and by polymerase chain reaction techniques. This second calcitonin messenger was expressed in 4/4 normal thyroids and 4/5 medullary thyroid carcinoma tissue samples. The expression of this second messenger is apparently a common occurrence in C cells whether normal or tumoral.

Amino Acid Sequence

Early diagnosis of the multiple endocrine neoplasia type 2 syndrome: consensus statement. European Community Concerted Action: Medullary Thyroid Carcinoma.

The diagnosis of medullary thyroid carcinoma by biochemical and genetic testing is possible in families with multiple endocrine neoplasia type 2. At an early stage total thyroidectomy usually cures the patient. As the clinical penetrance of the autosomal dominant, transmitted, multiple endocrine neoplasia type 2 gene is not complete, family screening is indicated for every new patient who presents with apparently sporadic medullary thyroid carcinoma. Problems related to a screening programme and early diagnosis have led the members of the European Community Concerted Action: Medullary Thyroid Carcinoma group to formulate a consensus on biochemical and genetic screening. For biochemical screening, measurement of basal and pentagastrin and/or calcium stimulated serum levels of calcitonin by radioimmunoassay are essential starting at the age of three and continuing annually until 35 years of age. Furthermore, annual screening for pheochromocytoma by measuring the urinary excretion of catecholamines and for hyperparathyroidism by serum calcium determination is indicated. Genetic screening using linked markers can be done with a 95% accuracy in informative families when DNA is available from at least two family members proven to be affected. Biochemical screening can thus be reserved for gene carriers, while those at low risk can be reassured. Combined biochemical and genetic screening for multiple endocrine neoplasia type 2 is important and effective for the cure of medullary thyroid carcinoma.

Adrenal Gland Neoplasms

Genetic analysis of 24 French families with multiple endocrine neoplasia type 2A.

The gene for multiple endocrine neoplasia type 2A (MEN2A) has been mapped to the pericentromeric region of chromosome 10 by linkage analysis. Thirty-four families with multiple cases of medullary carcinoma of the thyroid (MTC), including 24 families with origins in France, have been typed with nine polymorphic markers spanning the centromere of chromosome 10. No recombination was observed between the MEN2A locus and either of the four loci D10Z1 (lod score 12.79), D10S102 (lod score 6.38), D10S94 (lod score 7.76), and D10S34 (lod score 5.94). There was no evidence for genetic linkage heterogeneity in the panel of 34 families. Haplotypes were constructed for a total of 11 polymorphisms in the MEN2A region, for mutation-bearing chromosomes in 24 French families and for 100 spouse controls. One haplotype was present in four MEN2A families but was not observed in any control (P less than .01). Two additional families share a core segment of this haplotype near the MEN2A gene. It is likely that these six families have a common affected ancestor. Because the incidence of pheochromocytoma among carriers varies from 0% to 74% within these six families, it is probable that additional factors modify the expression of the MEN2A gene.

Adrenal Gland Neoplasms

Pheochromocytoma: a frequent indicator for MEN 2.

Pheochromocytoma is a frequent indicator of multiple endocrine neoplasia type 2A (MEN 2A); in the 35 French MEN 2A families in which a pheochromocytoma occurred first in some affected members, 30% of the patients had a pheochromocytoma as the first manifestation constituting 45% of all patients with pheochromocytomas. The finding of a pheochromocytoma is a strong indication for a search for medullary thyroid carcinoma and for initiating family screening.

Adrenal Gland Neoplasms

Somatostatin receptors and somatostatin content in medullary thyroid carcinomas.

Human medullary thyroid carcinomas from 19 patients were analyzed for their content in somatostatin (SRIF) receptors using receptor autoradiography with a SRIF-28 analogue and the SRIF octapeptide [Tyr3]-SMS 201-995 as iodinated radioligands. Four out of 19 cases were SRIF receptor positive with the SRIF octapeptide radioligand. These cases as well as four additional tumors were also positive with the SRIF-28 radioligand 125I-[Leu8, D-Trp22, Tyr25]-SRIF-28. High affinity binding sites pharmacologically specific for bioactive SRIF analogues, specifically located on tumor tissue, were identified. In some cases the SRIF receptors were distributed in a non-homogeneous pattern, with labelling occurring preferentially in highly differentiated tumor regions. Numerous cases were shown to have a high tumoral SRIF content measured by radioimmunoassay or immunohistochemical technique. However, there was no correlation between SRIF receptor status and tumor levels of endogenous SRIF. No correlation was seen between the clinical outcome or the survival of the patients and their tumoral SRIF receptor content. Whereas some medullary thyroid carcinomas seem to be a target for SRIF, the SRIF function in these tumors remains unclear. SRIF receptors in a group of medullary thyroid carcinomas may be useful morphological marker of these tumors and of potential interest for their in vivo localization.

Autoradiography

[Familial medullary thyroid cancer. Contribution of genealogy and genetics to the study of two families].

A geneological study made it possible to establish a link between two medullary thyroid carcinoma families from Normandy totalling 9 sick subjects, and a probable link with a third family. The study contributed to the diagnosis of multiple endocrine neoplasia type IIa, whereas the condition had been diagnosed for 6 years as familial medullary thyroid carcinoma, without phaechromocytoma. Group in these two families together increased the number of subjects tested, thereby facilitating genetic link analysis and enabling the link with markers of the disease on chromosome 10 to be asserted. The genetic study can now be used to detect individuals at risk, and with regular laboratory tests the diagnosis will be made at the "precancerous" stage. A genealogical study going back to the family-founding couple will increase the population which will benefit from screening in this region north of Rouen.

Adrenal Gland Neoplasms

The intratumoral immunoassayable somatostatin concentration is frequently elevated in medullary thyroid carcinoma. Results in 34 cases.

The current work has been performed by the Cooperative French Group of Medullary Thyroid Carcinoma (GETC). A systematic evaluation of RIA somatostatin (SRIH) was performed in 34 medullary thyroid carcinomas (MTC) (25 inherited, seven sporadic). Plasma SRIH was measured by radioimmunoassay in parallel with calcitonin (CT) and carcinoembryonic antigen (CEA). Immunoassayable SRIH was tested in fresh tumoral tissue samples from the same 34 MTC and, for comparison, in 10 nontumoral thyroid extracts (less than 6 pmol/g wet). Although plasma SRIH was only slightly elevated in two of 20 cases, tumoral SRIH was elevated in 70.6% of our MTC (10 to 3973 pmol/g). The chromatography of two tumoral extracts showed that somatostatin 14 was the major molecular form. We found no correlation (P greater than 0.1) between tumoral SRIH and the following: (1) tumor size (r = 0.227); (2) epidemiologic form of MTC (r = 0.144); (3) plasma SRIH (r = 0.045), plasma CT (R = 0.095) or (4) plasma CEA (r = 0.032). Thus, in the authors' experience, SRIH appears as a major product of tumoral C-cell in human MTC, even when plasma SRIH is normal and SRIH immunohistochemical staining is scarce. Multiple hormonal production of these tumors may explain its presence but SRIH may act also as a regulator, since negative influence of SRIH on CT is demonstrated in normal as well in tumoral conditions.

Adolescent

Immunoreactive gastrin-releasing peptide in medullary thyroid carcinoma.

We have previously shown that immunoassayable concentration of somatostatin (SRIH) was elevated in 70% of 34 consecutive medullary thyroid carcinoma (MTC) tissue samples. In the present study gastrin releasing peptide (GRP)-like immunoreactivity was measured in tissue extracts from these 34 MTC (25 inherited, 7 sporadic, 2 unclassified) and in 7 normal thyroid tissue. Plasma SRIH, calcitonin (CT) and carcinoembryonic antigen were assayed in all patients. Normal thyroid tissue contained less than 61 pmol GRP per g wet weight; in contrast GRP concentration was elevated (62-7800 pmol/g) in 32/34 tumor extracts. The distribution of tissue GRP values were similar in sporadic as well as in familial MTC. We found no significant correlation between tumor GRP concentration and plasma SRIH (r = -0.05), plasma CT (r = -0.24), or plasma carcinoembryonic antigen levels (r = -0.21). Tumor concentrations of immunoreactive GRP and SRIH were positively correlated when logarithmic transformation was used (P less than 0.01). Thus GRP, as well as SRIH, is a major product of tumoral C cells in human MTC when systematically evaluated in a large number of cases.

Adolescent

[Tumours markers. Calcitonin and carcinoembryonic antigen in medullary carcinoma of the thyroid (author's transl)].

Medullary carcinoma of the thyroid (MCT) is characterized by high circulating levels of calcitonin (CT) and of carcinoembryonic antigen (CEA), these markers enable the diagnosis of the tumour, the assessment of the efficacy of treatment and the detection of metastases at a subclinical stage. In 130 patients with a primary tumour and/or metastases, CT level was high. In 120 of them (92%), CEA level was also high. There was a positive correlation between levels of CT and of CEA, and both assays should be included in the preoperative examinations. Following removal of the tumour, normalisation of CEA levels takes several weeks, in contrast to CT where normalisation is rapid. Finally, these estimations may be used to detect familial forms at a subclinical stage. This enabled us to detect 16 new cases of MCT amongst 77 subjects studied.

Adrenal Gland Neoplasms

CEA and non-specific cross-reacting antigen (NCA) in medullary carcinomas of the thyroid.

An immunohistological study of five cases of medullary carcinoma of the thyroid was undertaken with monospecific antisera against CEA and NCA. CEA was present in different areas of the tumors: cell cytoplasm, cell membrane at its apical pole when the tumor had a pseudoglandular organization, deposits in the lumen of pseudoglands, and peri- and extra-cellular deposits. From these extra-cellular deposits, CEA could easily reach the circulation, thus causing rising serum levels up to high values. NCA was found in the same tumors and in the same localizations.

Antigens

Immunochemical studies on rabbit calcitonin.

Cross reaction studies using radioimmunoassays specific for human and porcine calcitonin showed that rabbit calcitonin is structurally more closely related to human than to porcine calcitonin.

Animals

[Hormone assays in polyadenomatosis (author's transl)].

Radioimmunological assays of peptidic hormone levels is now an essential procedure for the diagnosis of polyadenomatosis. The diversity of pathological associations found in polyadenomatosis cannot be completely explained by the unitary theories that have been proposed. Neither the APUD system, nor the common embryonic origin, nor the reduction in calcitonin excretion can fully explain the clinical picture: a logical explanation has still to be discovered. In practice, ectopic secretions are frequent in type 2 polyadenomatosis (medullary cancer, pheochromocytoma, neurofibroma, Marfan's syndrome, hyperparathyroidism) contrary to what is observed in type 1 cases (pituitary, parathyroid, pancreas).

Adrenocorticotropic Hormone

[Hypercalcemia and biologically active parathyroid hormone].

Hypercalcaemia always results in serious clinical sequalae and, if not treated, carries a most unfavourable prognosis. The clinician will gain major diagnostic help from an evaluation of the calcitonin and parathyroid hormone blood levels. With regard to parathyroid hormone we have developed, for the first time, a radioimmunoassay which is specific for the estimation of biologically active hormone in the circulation. We are dealing here with an unusual radioimmunological situation as the immunochemical sites are generally quite distinct from those associated with hormonal activity. We are presenting in this first paper the normal values and also the variations that occur in different types of hypercalcaemia. The comparison of these results with those obtained by the usual methods of estimation for parathyroid hormone assay lacking in biological activity shows the value of this new technique.

Calcitonin

[Calcitonin in the ultimobrancial body of Anguilla (Anguilla anguilla L.): cytologic localization by indirect immunofluorescence using human anti-salmon-calcitonin antibodies].

The localization of intracellular calcitonin has been achieved by immunofluorescence in the cytoplasm of all cells forming the epithelium of the ultimobranchial body of eels, using a human antiserum against synthetic Salmon calcitonin I. The specificity of the reaction is demonstrated by inhibition with synthetic salmon calcitonin (S.C.T.); the fluorescence is not inhibited by synthetic human calcitonin (H.C.T.).

Anguilla

Correlation between calcitonin and carcinoembryonic antigen levels in medullary carcinoma of the thyroid.

We have detected high values of carcinoembryonic antigen in the blood of patients suffering from medullary carcinoma of the thyroid (MCT). Levels of the antigen and calcitonin, the hormone which is specifically secreted by these tumours, are positively correlated. Stimulation of calcitonin secretion has no effect on carcinoembryonic antigen levels. Though the antigen assay is non specific for MCT, it may improve the diagnosis and follow-up of MCT-patients.

Calcitonin

[Pleural and intraspinal tumor with hypercalcitoninemia].

The authors report a case of probably ectopic secretion of calcitonin in a 35 year old woman suffering from a malignant tumour in a double intra- and extra-spinal form. Hormone levels returned to normal after complete excision of the tumour, in which it was impossible to demonstrate the presence of calcitonin despite a very marked secretory appearance by electron microscopy. Study of the literature concerning the secretion of calcitonin by malignant tumours indicates the high degree of contradiction concerning the origin and the significance of increased radio-immunological levels of this hormone, which it is not possible to use without criticism as a "marker" of carcinomas.

Adult