Biomedical subjects
G Milhaud
Publications and source records attributed to G Milhaud.
[Medullary thyroid cancer].
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Cell free translation of chicken calcitonin messenger RNA.
The primary step of calcitonin biosynthesis was studied in a normal organ: chicken ultimobranchial gland, a tissue particularly rich in calcitonin secretory cells. Poly(A)-rich RNA was extracted and purified from ultimobranchial organs and translated in a reticulocyte lysate in the presence of labelled methionine. Polyacrylamide gel electrophoresis of specific immunoprecipitates revealed a major band of Mr 14 500 and a band of Mr 13 300. Thus, in chicken the precursor of calcitonin is a Mr 14 500 polypeptide. The minor component of Mr 13 300 could represent limited processing by the reticulocyte lysate.
[Plurality of calcitonin-producing thyroid cancers].
Abnormal levels of calcitonin and carcinoembryonic antigen in plasma, and detectable amounts of these markers in tumours are not restricted to typical forms of medullary cancer of the thyroid but are also characteristic of some other tumours of the gland. The diagnosis of these tumours, therefore, should not rely entirely on histological findings but should include a search for specific biochemical markers in plasma and tissues.
The values of calcitonin and carcinoembryonic antigen in the treatment and management of nonfamilial medullary thyroid carcinoma.
Thirty-one patients were studied to evaluate the prognostic value of both calcitonin (CT) and CEA levels determined after the initial treatment in medullary thyroid carcinoma (MTC). Twenty-seven patients were evaluated three to nine months after initial treatment and four others afterwards. The CT and CEA levels were significantly higher and the survival rate lower in the eight patients with residual clinical disease as compared to the 19 patients in complete clinical remission. In patients in complete clinical remission, 11 had elevated CT level after treatment, and all had initial lymph node involvement. Five of these 11 relapsed and one died. None of the eight patients with normal CT levels after treatment relapsed. CEA levels were always abnormally high when patients relapsed. Fourteen patients in complete remission with high CT levels were followed for more than four years. Six had normal CEA levels and no relapse was observed. Eight of the 14 had pathological CEA levels and six of eight relapsed: five of these six patients presented CEA elevation from six to 36 months before the clinical relapse. In two of these six patients, a venous catheterization sampling method demonstrated infra clinical local recurrence. In two patients with liver metastases, the time course changes of CT and CEA levels were different and CEA appeared to be a more sensitive tumor marker than CT. These data are consistent with previous data concerning the values and limits of CT level for the management of MTC. Furthermore, this study demonstrates the prognostic significance of CEA determination in MTC. CEA appears to be a sensitive selective tumor marker capable of defining a high-risk subgroup.
Current techniques and recent advances in veterinary drug analysis with special reference to anthelmintics and tranquilizers.
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Pathogenesis and treatment of postmenopausal osteoporosis.
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Characterization of target organs for calcitonin in lower and higher vertebrates.
The bindings of calcitonin was investigated in trout bone, kidney and gill and rat bone and kidney. Specific binding of calcitonin was observed in all tissues tested except fish kidney membranes. The affinity constants for the sites of high affinity-low capacity (in trout bone and rat kidney) or for the unique site (in trout gill and rat bone) were of the same order of magnitude (2.0-9.0 x 10(9) M-1), the number of binding sites per mg of protein being higher in rat bone homogenates than in other tissues. These studies strongly support the theory that the gill in fishes is likely to perform some of the functions of the kidney in mammals.
(Dichloromethylene)diphosphonate-induced impairment of T-lymphocyte function.
The daily subcutaneous administration of (dichloromethylene)diphosphonate (clodronate) to 3-day-old normal inbred Wistar-Furth rats for 30 days produces osteopetrotic bone lesions resembling those of the osteopetrotic mutants. Furthermore, tooth eruption is prevented, growth slows down, and signs of runt disease appear. The weight of the thymus is decreased, and T cells from the thymus and spleen respond weakly to mitogens. These thymic disorders associated with defective bone resorption are very similar to those previously reported in the osteopetrotic mutant op rat and support the hypothesis of a link between the thymus and normal bone modeling and remodeling.
Calcium regulating hormones during the estrous cycle of the rat.
Plasma levels of calcium (Ca), phosphate (P), calcitonin (CT), parathyroid hormone (PTH), and prolactin (PRL) were measured at 8, 13, and 17 hr during the 4-day estrous cycle of the rat. Ca levels fell throughout the day during proestrus (PE) and estrus (E). In contrast Ca rose transiently during diestrus (D1, D2). P levels fluctuated inconsistently at all stages of the cycle with the exception of E where P levels were significantly higher at 13 hr. CT levels showed an increase during D1 and D2 and fell to their lowest values during E, at 13 hr. Daily fluctuations in each stage were also recorded. Variations of PTH levels during the estrous cycle were minor. PRL levels increased sharply during PE. No direct relationship between PRL secretion and CT secretion could be established. These results indicate that CT but not PTH varies specifically in relation to the estrous cycle. They suggest that there is a link between sexual hormones and CT, apparently independent of plasma calcium levels.
Lack of a T-cell dependent subpopulation of macrophages in (dichloromethylene) diphosphonate-treated mice.
In Cl2MDP-osteopetrotic mice, one subpopulation of thioglycollate-induced peritoneal exudate macrophages (M phi) is missing. This subpopulation is precisely the one whose differentiation is known to be dependent on T-lymphocytes, as it is also missing in the athymic nu/nu mice. Cl2MDP-induced osteopetrosis being partially attributable to deficient osteoclastic bone resorption, raises the possibility that this missing M phi subpopulation might represent the precursors of osteoclasts. It is suggested from this work that the interplays between T-cells and M phi, so well known in immunity and inflammation, may also be relevant to osteoclastic differentiation and therefore, to bone remodeling.
A baby with Di George syndrome treated with bovine thymic extracts: a 3.5 yr analysis of variations in the distribution of lymphocytes characterized by three tests of cell mediated immunity and electrophoretic mobility.
This report concerns a baby with the features of Di George syndrome. Bovine thymic extracts prepared in this laboratory were used to treat the baby between the ages of 1 and 18 months. A favourable evolution of the illness was noticed, suggesting the diagnosis of Di George syndrome in its partial form and/or a favourable response to the treatment with thymic extracts. The number of E-rosette forming T-lymphocytes in blood remained low during the 3.5 yr of the observation. The in vitro response of peripheral blood lymphocytes to phytohemagglutinin and to allogenic cells slowly increased during this period of time. Surprisingly, no change in the proportions of lymphocytes of high electrophoretic mobility and low electrophoretic mobility was observed, in contrast to the gradual change usually observed in normal individual age-matched controls.
Calcitonin and carcinoembryonic antigen in poorly differentiated follicular carcinoma.
Previous studies have shown that certain patients suffering from poorly differentiated follicular carcinoma (PDFC) of the thyroid had high levels of calcitonin (CT) and carcinoembryonic antigen (CEA) in the plasma. In this work, both CT and CEA were localized in tissue sections obtained at operation from patients suffering from PDFC. The results confirm the hypothesis that certain cases of PDFC are in fact CT-secreting tumors and represent another type of thyroid neoplasma. Patients suffering from PDFC should be screened using both CT and CEA assays.
Action of calcitonin on the atherosclerotic modifications of brain microvessels induced in rabbits by cholesterol feeding.
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Gene dependent differences in malignant osteopetrosis as evidenced by cellular induction of the disease.
Osteopetrosis was induced in lethally irradiated normal rats by cell infusion prepared from spleens of the osteopetrotic (op) mutant littermates. However, similar attempts to induce osteopetrosis in another strain of osteopetrotic rats, namely the "toothless" (tl) rats, were unsuccessful. This discrepancy between op and tl rats with regard to the transmission of the disease to normal littermates, parallels the response of the respective mutants to treatment by normal bone marrow cells: the op rat is cured, not the tl rat. The present findings confirm the cellular origin of osteopetrosis in the op rat, whereas the origin of the defect in the tl mutant remains obscure.
Calcium metabolism in multiple myeloma.
45Calcium metabolism and circulating levels of iPTH (N-terminal fragment) and iCT were investigated in normocalcemic patients with multiple myeloma (12) in an attempt to ascertain early changes in calcium metabolism, which may occur before hypercalcemia develops. The same parameters were also investigated in patients with senile osteoporosis (11), corticosteroid-induced osteoporosis (6), Paget's disease (6) and controls without bone disorders (13). In the myeloma group, the exchangeable calcium pool (7,678 +/- 321 mg) was significantly higher (P less than 0.01) than in the control group (4,405 +/- 374 mg), the senile osteoporosis group (4,108 +/- 407 mg) and the corticosteroid-induced osteoporosis group (3,015 +/- 161 mg) and nearly as high as in the Paget's disease group (8,876 +/- 1,173 mg). Calcium pool turnover rate was higher in the myeloma group than in controls, as were bone anabolism and bone catabolism, although differences were not statistically significant. There were no statistically significant differences among the groups in the plasma iPTH or iCT, although the mean value of the latter was higher in the myeloma group than in controls (86 +/- 24 vs. 47 +/- 13 pg/ml). These data suggest that an increase in the exchangeable calcium pool and in turnover rate may occur early in the course of multiple myeloma, preceding the development of hypercalcemia. The role of some homeostatic mechanisms in maintaining normal plasma calcium levels in multiple myeloma despite increased bone calcium resorption is discussed.
Resistance to adjuvant arthritis induced by a genetic mutation, osteopetrosis.
Adjuvant arthritis stands as the closest model to human rheumatoid arthritis. A genetic mutation (op) recognized to provoke osteopetrosis in rats, completely inhibits their ability to develop adjuvant arthritis. Osteopetrosis in the op mutant is linked to deficiencies in T-lymphocytes and macrophages functions. Therefore this animal model may be helpful for a better understanding of the immunoregulation impairment involved in adjuvant arthritis.
Aminoterminal parathyroid hormone radioimmunoassay to evaluate bone status in renal failure.
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