Proceedings: Serum T3-RIA. A reevaluation.
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Biomedical subjects
Publications and source records attributed to P Thomopoulos.
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1. Dexamethasone selectively reduced the number of the type A (75 kD) receptors whereas 1,25-dihydroxyvitamin D3 reduced the number of both A (75 kD) and B (55 kD) receptors, without any change of their dissociation constants (3-4 x 10(-10) M and 1-2 x 10(-9) M respectively). The level of the type A (75 kD) TNF receptor mRNA was increased following treatment with either steroid. 2. Other agonists which either down-regulated (phorbol dibutyrate) or up-regulated (dibutyryl cAMP and recombinant GM-CSF) rTNF alpha binding also increased the level of this mRNA species. 3. The data suggest that these steroids might alter post-transcriptional event(s).
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Binding of 20-[3H]-phorbol 2, 13-dibutyrate [( 3H] PDB) to intact human K 562 cells was characterized. Specific binding of [3H] PDB to K 562 cells at 20 degrees C or 37 degrees C reached a maximum within 15-20 min. Maximal specific [3H] PDB binding to K 562 cells was followed by a decline (down regulation) of radioacticity. This down regulation was temperature dependent; no loss of radioactivity occurred by 1 hour at 4 degrees C. When [3H] PDB binding was carried out a 4 degrees C, [3HDB bound to K 562 cells in a rapid, specific, and reversible manner. Phorbol esters which lack tumor-promoting activity, did not inhibit [3H] PDB binding. A Scatchard analysis was compatible with one class of binding sites, Kd = 50 nM and about 2 X 10(5) binding sites per cell. Human serum inhibited specific binding of [3H] PDB. The effect of several chemical compounds on [3H] PDB binding was also investigated. Most of the compounds tested such as butyrate, hemin, gamma-globulins, transferrin, insulin, EGF, and albumin failed to significantly affect the binding of [3H] PDB. In contrast, retinoic acid and quinacrine significantly affected the binding of [3H] PDB: retinoic acid induced a marked increase of [3H] PDB binding which was dose dependent; quinacrine induced a decrease of [3H] PDB binding, even at low concentration.
In man, the assay of insulin receptors is performed on circulating monocytes or erythrocytes. In physiology, insulin binding decreases with age; it is lower in women during the luteal phase of the menstrual cycle or during administration of oestrogen-progestogen oral contraceptives; it exhibits diurnal variation; it increases after physical training; it depends on the diet, being inversely correlated with its carbohydrate content; finally, rapid variations in binding affinity are observed after glucose ingestion or after breakfast. In pathology, obese people are resistant to the effects of insulin and they have decreased numbers of receptors on blood cells; short-term fasting induces an increase in the binding affinity, while a long term hypocaloric diet leads to an increase in receptor numbers. Similarly non-insulin-dependent, maturity onset diabetics, even without overweight, have low numbers of binding sites, which are increased by diet or after treatment by sulfonylureas. In the syndrome of insulin resistance and acanthosis nigricans, there is a decrease in hormone binding, which is either primary (Type A) or is secondary to the effects of circulating antibodies to the insulin receptor (Type B). In acromegaly, insulinomas, liver cirrhosis and acute viral diseases the binding of insulin is decreased. On the contrary, variable results have been reported in cases of lipoatrophic diabetes, leprechaunism, uremia and glucocorticoid administration. Finally, an increase in insulin receptors has been observed in anorexia nervosa and in insulino-penic diabetes.
OBJECTIVE: We wished to evaluate the influence of postoperative radiotherapy on the incidence of tumour regrowth in non-secreting pituitary adenomas. METHODS: The cases of 57 patients with clinically non-secreting pituitary adenomas were retained for a retrospective study of long-term disease-free survival out of a series of 66 patients treated between 1970 and 1988. Thirty-three patients were treated by surgery only (Group A), and twenty-four by surgery followed by external radiotherapy (Group B). Disease-free survival curves were calculated according to the Kaplan-Meyer method and compared by the Logrank test. The impact of some supposed prognostic parameters--such as tumoural volume, macroscopic features of invasiveness and quality of surgical resection--on the disease-free survival was analyzed according to the Logrank adjusted test. RESULTS: The mean follow-up duration was 7.1 +/- 6.2 years, and eleven patients relapsed: nine in group A (27.0%) and two in group B (8.3%), with respective free intervals of 6.1 +/- 5.0 years and 9.6 +/- 2.4 years. Statistical analysis of the disease-free survival curves confirmed that this difference was significant (p < 0.01). Further analysis of putative risk factors (the importance of extrasellar extension and the estimated quality of surgical resection) was attempted, but it did not reach statistical significance. CONCLUSIONS: Radiotherapy is effective in preventing post-operative regrowth of non-secreting pituitary adenomas. Whether it should be systematically proposed or reserved to selected cases remains to be evaluated.
The respective role of p55 and of p75 TNF receptors in mediating the constitutive or the regulated cytotoxic response of U937 cells was discriminated using monoclonal antibodies directed against each receptor type, respectively htr-9 and utr-1. Cytotoxicity was mediated by the p55 receptors. The p75 receptors were also implicated as it reduced 100 fold the maximal active dose of rTNF-alpha and 15 fold the EC50 value. Dexamethasone potentiated and 1,25-dihydroxyvitamin D3 abolished rTNF-alpha induced cell growth arrest and toxicity. Dexamethasone was required to be present for rTNF-alpha to be active. It increased the maximal response whether toxicity was mediated through only p55 or both p55 and p75 receptors, without changing the respective EC50 values for rTNF-alpha. Therefore dexamethasone did not affect the interactions between p55 and p75 receptors nor between these receptors and their ligand, suggesting that it regulates the cytotoxicity at a post-receptor level. 1,25-dihydroxyvitamin D3 drove the promonocytic U937 cells resistant to rTNF-alpha by short-term effect. Comparing the effect of 1,25-dihydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 derivatives on the cytotoxicity to their effect on cell surface receptor expression, revealed that the capacity to induce resistance to rTNF-alpha was restricted to those steroids which down-regulated the p55 receptors. Therefore, resistance to rTNF-alpha could be related to an early effect of 1,25-dihydroxyvitamin D3 on p55 receptors. Finally, the results suggest that dexamethasone and 1,25-dihydroxyvitamin D3 regulate TNF-alpha induced cytotoxicity by affecting processes probably related to the functions of the p55 receptors.
Two cases of Riedel's thyroiditis demonstrated the difficulties encountered in diagnosis. In the first case, subtotal thyroidectomy was performed due to compressive goiter. The intraoperative macroscopic aspect suggested Riedel's thyroiditis. The pathology report also discussed the diagnosis, despite a major lymphoid component, as dense fibrosis had multilated the thyroid parenchyma. Subsequent clinical course led to the diagnosis of lymphoma. The clinical presentation in the second case was classical with rapid increase in size of a hard thyroid gland. Histology was however atypical showing calcifications and liquid cysts within the fibrous thyroid tissue. The initial signs of Riedel's thyroiditis, a very rare disease, usually suggest neoplasia: ligneous compressive goiter with deep adherences. Histologically, there is invasive fibrous thyroiditis with highly suggestive occlusive phlebitis in certain cases. The origin of the disease remains obscure. The differential diagnosis between a sclerosing form and lymphoma is particularly important for therapeutic management.
OBJECTIVES: The purpose of the study is to determine if pituitary Magnetic Resonance Imaging (MRI) can predict the outcome of transsphenoidal surgery in patients with Cushing's disease. METHODS: Fifty four patients were divided in three groups according to MRI findings: those with a well circumscribed focal lesion clearly separated from the cavernous sinus (group 1, n = 24), those with adenomas in close contact with the cavernous sinus (group 2, n = 18), and those with no identified lesion (group 3, n = 12). RESULTS: The adenoma is found on the predicted side in 97,6% of the cases with positive MRI. A histologically proven adenoma is found in 96, 100 and 33% of the cases in groups 1, 2 and 3, with successful outcome in 91, 94 and 58% of the patients respectively. In group 2, surgery failed in a patient in whom tumoral tissue surrounded the internal carotid artery, but succeeded in two other cases in whom a MRI involvement of the cavernous sinus was suspected. CONCLUSION: We confirm the excellent localization value of MRI. Failure due to cavernous sinus involvement can be predicted only when MRI shows that the adenomatous tissue surrounds the carotid artery. In cases of negative MRI, the outcome is less favorable.