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Biomedical subjects

M Schlumberger

Publications and source records attributed to M Schlumberger.

At least 145 records · Page 8Linked to original sources
PubMed1995

Genetic alterations in thyroid hyperfunctioning adenomas.

Thirty-seven thyroid autonomously hyperfunctioning adenomas were screened for mutations in the TSH receptor (TSHR), G alpha s (gsp), and ras genes. Polymerase chain reaction-amplified fragments of the TSHR C-terminal part (exon 10), the G alpha s (exons 8 and 9), and the three ras genes were obtained from the genomic DNA extracted from 37 tumors and their adjacent normal tissues and were studied by direct nucleotide sequencing and hybridization with synthetic probes. A point mutation in the third intracellular loop (codon 623) of the TSHR was found in 3 of 37 adenomas studied. This mutation codes for a change (Ala to Ser) in the TSHR structure and is somatic and heterozygotic. Constitutive activation of the TSHR was demonstrated by an increase in basal cAMP levels after transfection of Chinese hamster ovary cells with a mutated Ser623-TSHR complementary DNA. Nine gsp[00ae]MDRV[00af]- and one ras-activating mutations were also detected. No simultaneous alteration of the studied genes was present. Thus, in hyperfunctioning thyroid adenomas, our data suggest that a mutational activation of the TSHR and gsp genes may play a tumorigenic role through constitutive activation of the cAMP pathway.

Adenoma↗
PubMed1995

Radiolabeled somatostatin analog scintigraphy in differentiated thyroid carcinoma.

UNLABELLED: After intravenous administration of a radiolabeled somatostatin analog (octreotide), an image of the thyroid gland is frequently observed; few data are available, however, on somatostatin receptors in epithelial thyroid cells assessed in vitro and on images of differentiated thyroid carcinoma (DTC) with pentetreotide scintigraphy. METHODS: In four patients with metastatic thyroid carcinoma, whole-body scintigraphy was performed 4 to 48 hr after injection of 110 MBq of 111In-pentetreotide. The results were compared to data obtained with other imaging modalities, including scintigraphy performed after administration of a therapeutic dose of 131I. RESULTS: There were positive foci in distant metastases on 111In-pentetreotide scintigraphy. Pentetreotide scintigraphy was positive in two patients with an "insular" form of DTC, one of whom had a positive (faintly) 131I scan. Of the other two patients with papillary DTC without radioiodine uptake, only one exhibited a certain degree of pentetreotide scintigraphy positivity in distant metastases. CONCLUSION: These results show promise for exploration of insular thyroid carcinoma and suggest that these carcinomas may possess functional differentiation features, including somatostatin receptors.

Bone Neoplasms↗
PubMed1995

[Thyroid tumors after irradiation].

Epidemiological studies have shown an increased incidence of thyroid tumors after external irradiation during childhood. These studies have shown a long latency and have pointed out risk factors, related either to the subject (young age, female sex) or to the radiation (dose, fractionation, protaction). Irradiation by Iodine 131 in adulthood does not seem to increase the risk of thyroid tumor but in childhood data are too scarce to allow any conclusion. Similarly, the risks following low radiation doses and/or protacted radiation exposure are still matter of debate.

Adult↗
PubMed1995

[Endocrine involvement in immunotherapy].

Thyroid dysfunction and abnormalities in corticosteroid regulation were observed after clinical use of cytokines (IL2, IFN alpha), molecules with immunostimulating properties. Interleukin 2 administration induces hypothyroidism often associated with anti-thyroglobulin and anti-thyroid microsomal antibody. All these features recall Hashimoto's thyroiditis. Frequency of thyroid dysfunction during immunotherapy varies according to authors between 20 and 40 percent of all patients treated. A correlation between thyroid dysfunction and response to IL2 therapy was reported. Hypothyroidism and hyperthyroidism with development of anti-TSH receptor antibody are observed after IFN alpha administration. An auto-immune aetiology of these thyroid side effects was suggested because fine needle aspirates of the thyroid of these patients, when available, revealed a mixed cellular infiltrate with lymphocytes and histiocytes and immunocytochemical staining showed strong HLA-DR expression of all thyrocytes. Involvement of lymphokine activated killer (LAK) or direct effect of cytokines on thyroid are also possible. After intravenous injection of IL2, a marked increase in ACTH levels occurred, peaking at 4 hour with a comparable peak in cortisol level at 5 hour. Expression of IL2-Receptor in pituitary cells suggests a direct action of IL2 on anterior pituitary. Nevertheless, indirect action of IL2 via induction of other cytokines or possible secretion of ACTH by activated lymphocytes, cannot be ruled out. Testosterone serum levels decreased significantly after IL2 or IFN alpha administration. It is noteworthy that these endocrine effects induced by cytokines may modulate the clinical efficacy of these substances underlying the bi-directional communication between the immune and endocrine system.

Adrenal Cortex Hormones↗
PubMed1995

Comparison of radiolabeled octreotide and meta-iodobenzylguanidine (MIBG) scintigraphy in malignant pheochromocytoma.

METHODS: The results of in vivo somatostatin scintigraphy were correlated with those of MIBG from 14 patients, aged 22-66 yr, with metastatic pheochromocytoma (10 patients), malignant paraganglioma (3 patients) and metastatic ganglioneuroblastoma (1 patient). Twelve patients had elevated catecholamine excretion. A dynamic study and serial whole-body scans (4-48 hr) were obtained after injection of 130-187 MBq of 111In-DTPA-Phe-1-octreotide. When indicated, SPECT imaging was done. The results were compared to MIBG scans obtained after a diagnostic or a therapeutic dose. RESULTS: Three patients with more than 20 tumor sites on MIBG scans had only 1-9 sites on 111In-octreotide scintigraphy. Two patients had no MIBG uptake but one had lung uptake on octreotide scintigraphy. In the other 9 patients with a total of 41 foci of MIBG uptake, 33 sites of 111In-octreotide uptake are found. All positive images with octreotide scintigraphy were seen at or before 4 hr, but the contrast improved at 24 hr. Uptake intensity was lower with 111In-octreotide than MIBG and the number of tumor sites was higher with MIBG. However, seven foci were positive only on octreotide scintigraphy and six of them could not be confirmed by other imaging modalities. CONCLUSION: Use of octreotide to identify somatostatin receptors seems promising, especially when results from MIBG scans are negative. Moreover octreotide images could aid in determining a treatment regimen as well as establishing the extent of disease and prognosis.

3-Iodobenzylguanidine↗
PubMed1995

Somatostatin receptor imaging: a preliminary experience in forty-nine patients.

We report our experience with the 111In-pentetreotide scanning of 47 adult patients presenting with neuroendocrine tumors (n = 38) or malignant pheochromocytomas or related tumors (n = 9), and 2 children with metastatic neuroblastomas. A dynamic study was performed after i.v. administration of 50-190 MBq of 111In-pentetreotide followed by a whole body scan at 1.5-4 hours and at 24 hours. Where indicated, tomoscintigraphy or a dual isotope bone, liver or kidney scan was performed in order to improve the anatomical definition. Lesions were visualized in the earliest phases of the examination but contrast was enhanced on delayed images due to an improved signal to background ratio. In 9/49 patients, octreotide scan (OS) detected unknown tumors sites. On the other hand, the lesion uptake of 111In-pentetreotide varied, and not all the sites shown by other imaging modalities were visualised, probably due to differences in membrane receptor expression. In conclusion, OS can be useful in the diagnosis, follow-up and therapeutic management of neuro-endocrine tumors. Further investigations are required to assess the role of OS in other pathologies. Short title: Somatostatin receptor imaging.

Adolescent↗
PubMed1994

Oncogenic potential of guanine nucleotide stimulatory factor alpha subunit in thyroid glands of transgenic mice.

Transgenic mice have been used to address the issue of the oncogenic potential of mutant guanine nucleotide stimulatory factor (Gs) alpha subunit in the thyroid gland. The expression of the mutant Arg-201-->His Gs alpha subunit transgene has been directed to murine thyroid epithelial cells by bovine thyroglobulin promoter. The transgenic animals develop hyperfunctioning thyroid adenomas with increased intracellular cAMP levels and high uptake of [125I]iodine and produced elevated levels of circulating triiodothyronine and thyroxine. These animals demonstrate that the mutant form of Gs alpha subunit carries an oncogenic activity, thus supporting the model that deregulation of cAMP level alters growth control in thyroid epithelium. These animals represent models for humans with autonomously functioning thyroid nodules.

Animals↗
PubMed1994

Screening for adrenal medullary disease in patients with medullary thyroid carcinoma.

Adrenal medullary disease (AMD) is clinically silent in most patients with medullary thyroid carcinoma (MTC). It was screened yearly by urinary measurements of catecholamines and derivates, and by abdominal ultrasonography (US) in a series of 174 patients with MTC. In cases with suspicion of AMD, abdominal computerized tomography and scintigraphy with meta-iodobenzylguanidine were also performed. AMD was discovered in 10 patients (one adrenal medullary hyperplasia and 9 pheochromocytomas). Three patients were already known to belong to a type II multiple endocrine neoplasia (MEN-2a) family and two had a MEN-2b syndrome. In 5 patients previously considered as having either a sporadic (4 cases) or a familial type of isolated MTC (one case), the occurrence of AMD led to diagnose a MEN-2a syndrome. The diagnostic values of the tests were evaluated by a case-control study. Urinary metanephrine plus normetanephrine (MN+N) had an acceptable sensitivity (0.8) and specificity (0.8). The other urinary tests had a high specificity (range: 0.8 to 1) but a poor sensitivity (range: 0.1 to 0.5). US had a high sensitivity (0.8) and a specificity of one. MN+N and US performed yearly constitute a simple and efficient strategy to screen for AMD in patients with MTC.

Adolescent↗
PubMed1994

Selective venous sampling catheterisation for localisation of persisting medullary thyroid carcinoma.

Selective venous sampling catheterisation was performed in 19 patients with medullary thyroid carcinoma without known distant metastases for persistent hypercalcitoninaemia after surgery. Calcitonin (CT) gradients were found in the neck and/or the mediastinum in 18 patients and in five patients at distant sites also. After venous catheterisation, 13 patients were subjected to repeat surgery. Neck and/or mediastinal tumour foci were found in 12 patients at the sites of the CT gradients. Of these, nine patients had only cervicomediastinal CT gradients: after reoperation, the serum CT level normalised in one, significantly decreased in five, and did not change in three, and no neck relapse occurred after a mean follow-up of 5.3 years. Distant metastases emerged clinically in all five patients with distant gradients and in only one of the 14 patients with no distant gradient. In conclusion, selective venous catheterisation is the most sensitive tool for the localisation of residual disease and for the early detection of distant metastases. However, in patients with only local disease, biochemical cure is rarely obtained after reoperation.

Adolescent↗
PubMed1994

Processing by factor analysis of dynamic dual isotope studies using 99Tcm and 201Tl within a middle energy band. Evaluation in thyroid nodule malignancy.

Simultaneous investigations with two isotopes are currently restricted because of spectral overlap. The factor analysis of spectral and dynamic structures (FASDS) method is shown to achieve accurate spectral separation. In addition, it estimates underlying dynamic mechanisms. Twenty-six patients were injected simultaneously with 99Tcm-pertechnetate and 201Tl-chloride to assess the malignancy of solitary thyroid nodules. List-mode acquisition of spectral, temporal and spatial coordinates of events allows the reconstruction of an image sequence indexed by time and energy. FASDS proceeds in two steps. First it yields both dynamic and spatial information related to each isotope (99Tcm and 201Tl) and partially removes the scatter component. Then it estimates the underlying kinetics and associated spatial distributions of each isotope. Using the 201Tl component, an index was derived from the uptake ratio between nodules and normal thyroid tissue. Concerning the detection of malignant nodules the method indicated no false negative in our limited group of 26 patients. One false positive result was found which could not be classified by the investigation of the 201Tl dynamic components contained in the reconstructed 201Tl factor sequence.

Factor Analysis, Statistical↗
PubMed1994

Pheochromocytoma as the first manifestation of von Hippel-Lindau disease.

BACKGROUND: von Hippel-Lindau disease is an autosomal dominant disorder characterized by the development of hemangioblastomas in the cerebellum, spinal cord, and retina, renal cell carcinoma and cysts, pancreatic cysts, and pheochromocytoma. METHODS: We have studied a series of 36 French patients affected with von Hippel-Lindau disease pheochromocytoma. Thirty (83%) of them were diagnosed as having von Hippel-Lindau disease because the disease occurred in a familial von Hippel-Lindau disease setting; six (17%) were diagnosed as having von Hippel-Lindau disease because they displayed another characteristic manifestation of that disease. RESULTS: The mean age at pheochromocytoma diagnosis was 29 +/- 14 years (5 to 62 years). Bilateral tumors were documented in 15 (42%) cases, paraganglioma was associated with adrenal pheochromocytoma in four cases, and malignant pheochromocytoma occurred in three cases. Prevalence of pheochromocytoma revealing von Hippel-Lindau disease was 20 (53%) out of 36. In six cases pheochromocytoma was the only manifestation of the disease. CONCLUSIONS: In the interest of the patients themselves and of family members who are at risk, search for von Hippel-Lindau disease must be systematic in the presence of pheochromocytoma. Basic checkup may be completed with familial inquiry, ophthalmoscopy, cerebral magnetic resonance imaging, abdominal ultrasonography, and computed tomography-scan for detection of latent lesions. In the future, after characterization of von Hippel-Lindau disease gene mutations, molecular diagnosis is going to be possible in individual patients.

Adolescent↗
PubMed1993

Analysis of p53 antibodies in patients with various cancers define B-cell epitopes of human p53: distribution on primary structure and exposure on protein surface.

p53 antibodies have been found in sera of patients with breast and lung carcinomas and in children with B-lymphomas. We report here the presence of p53 antibodies in sera of patients with 11 different types of cancer. The frequency of seropositives for p53 varied among the different types of cancer, but a correlation with the frequency of p53 gene alteration was established. Using a powerful peptide enzyme-linked immunosorbent assay, we demonstrated that the immune response of patients with p53 antibodies was restricted to a small subset of peptides localized in the amino and carboxy termini of p53, whatever the type of cancer. Given the similarities of the patterns of immune responses in patients with p53 antibodies and animals hyperimmunized with human p53, we propose that the p53 humoral response is the result of a self-immunization process which is itself the consequence of p53 protein accumulation in tumor cells.

Amino Acid Sequence↗