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Biomedical subjects

B Delemer

Publications and source records attributed to B Delemer.

29 records · Page 2Linked to original sources
PubMed1992

Autocrine biological effects of glycosyl inositol phosphate produced by reconstituted pig thyroid follicles: role of pertussis toxin sensitive G proteins.

We examine the autocrine activity of glycosyl inositol phosphate (InP-gly) on thyroid metabolism. The cAMP accumulation promoted by thyrotropin (TSH) or forskolin was modulated by InP-gly, stimulated by the lowest tested concentration (10(-8) M) and progressively inhibited by higher concentrations. Iodide uptake and iodine organification were decreased in a concentration-dependent manner by InP-gly alone, or in the presence of TSH. The IAP component of pertussis toxin blocked the inhibitory action of InP-gly on cAMP accumulation by reconstituted thyroid follicles (RTF), suggesting the participation of Gi protein. But the same treatment with IAP was without effect on iodine metabolism, suggesting that there is a second target for InP-gly, more distal than Gi protein, or coupled to another G protein which is insensitive to the toxin.

Animals↗
PubMed1992

Modification of the amounts of G proteins and of the activity of adenylyl cyclase in human benign thyroid tumours.

The possibility that a TSH post-receptor-binding defect is responsible for the pathogenesis of benign thyroid tumours was studied. Thus, we attempted to determine in hyperfunctioning (hot) nodules and non-functioning (cold) nodules whether the functional activity or the amount of G proteins were modified in comparison with surrounding normal tissues. The adenylyl cyclase response to agonists that bypass the TSH-receptor complex (forskolin, guanosine 5'- (beta.gamma-imido)triphosphate (Gpp(NH)p) or [AIF4]-) was studied on membranes from tumorous and adjacent normal thyroid tissues. We also examined the ability of G proteins to be ADP-ribosylated by cholera toxin (CT) or pertussis toxin (PT), and quantified G proteins by Western blot analysis with specific antisera directed against Gs alpha and Gi alpha subunits. Basal adenylyl cyclase activity was unchanged in hot tumours compared with normal tissue whereas the stimulation of adenylyl cyclase by Gpp(NH)p or [A1F4]- (which act directly on Gs) as well as by forskolin (which acts on the catalyst) was significantly (P less than 0.05) decreased in five of seven nodules studied. Two types of response were found in cold nodules, depending upon whether they were microfollicular or macrofollicular tumours. Basal as well as stimulated adenylyl cyclase activity was increased (0.02 less than P less than 0.05) in microfollicular tumours. In contrast, in macrofollicular tumours basal adenylyl cyclase was unchanged whereas stimulated adenylyl cyclase activity was decreased (0.02 less than P less than 0.05). The ability of Gs or Gi to be ADP-ribosylated by CT or PT respectively was maintained in tumorous tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1992

[Role of adrenocortical scintigraphy in the exploration of incidentally discovered tumors].

To determine the utility of adrenocortical scintigraphy with I131-6 beta-iodomethyl-19-nor-cholesterol (NP59) in incidentally discovered adrenal masses, we studied 12 patients with a unilateral adrenal mass and without other primary tumors or signs of pheochromocytoma or hyperfunctioning adenoma. Ten patients had an adenoma (size: 12 to 35 mm), the diagnosis was made by surgery or by no change in size on repeated CT scans. The NP59 scintigraphy showed an increased uptake on the side of the tumor in 8 cases with a decreased uptake of contra-lateral gland in 7 cases. Hormonal investigations of glucocorticoid function suggested supranormal or fluctuant cortisol secretion in 5 cases as assessed by moderately elevated urinary free cortisol or by incomplete dexamethasone suppression test. These abnormalities disappeared after surgery. Two patients had normal bilateral uptake of NP59, the sizes of the tumors were 12 and 20 mm. Two patients had an extra-adrenal tumor. The NP59 scintigraphy showed a moderately decreased uptake on the side of the hematoma of one patient and a compression of the normal adrenal by ganglioneuroma of the other patient. Our results and those of other authors suggest that positive NP59 scintigraphy could confirm the cortical nature of an incidentally discovered adrenal mass, probably an adenoma that must be followed up morphologically and functionally. No uptake by a tumor greater than 2 cm suggests a primary malignancy or extra-adrenal origin which must be diagnosed by invasive methods.

Adenoma↗
PubMed1991

Alteration of the functional activity of Gs protein in thyrotropin-desensitized pig thyroid cells.

Changes in the sensitivity of adenylyl cyclase observed in pig thyroid cells cultured 2 days in the presence of thyroid-stimulating hormone (TSH) or forskolin were assessed by examining the properties of Gs protein. Chronic treatment of thyroid cells with various concentrations of TSH (0.01-1 mU/ml) or forskolin (0.1-10 microM) increased the response of adenylyl cyclase to a further stimulation by forskolin or NaF + AlCl3 ([AlF4]-). In contrast, the enzyme activation promoted by guanosine 5'-(beta,gamma-imido) triphosphate (Gpp(NH)p) was markedly affected. There was a significant increase in adenylyl cyclase activation by Gpp(NH)p in membranes from cells treated with low concentrations of TSH (less than or equal to 0.1 mU/ml) or forskolin (less than or equal to 1 microM) but a significant decrease in membranes from cells cultured with a higher concentration of TSH (1 mU/ml) or forskolin (10 microM). This decrease in Gpp(NH)p-stimulated adenylyl cyclase activity was mimicked by 8-bromo-cAMP but not by 1,9-dideoxyforskolin, a forskolin analogue which has lost its ability to activate adenylyl cyclase. There was a good correlation with the ability of Gs protein to be ADP-ribosylated by cholera toxin: labeling of Gs protein decreased following chronic treatment of thyroid cells with TSH (1 mU/ml) or forskolin (10 microM). In contrast, under the same experimental culture conditions a slight but significant increase in the quantity of Gs subunits was observed by immunoblotting analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

High permanent plasma adrenaline levels: a marker of adrenal medullary disease in medullary thyroid carcinoma.

Increases in urinary, plasma and tumour adrenaline have been previously observed in MEN II patients with phaeochromocytoma. However, the sensitivity of adrenaline for early detection of adrenal medullary disease has not been accurately evaluated. Twenty-five patients with medullary thyroid carcinoma (MTC) histologically confirmed but without clinical or biological evidence of phaeochromocytoma have been studied. Medullary adrenal status was evaluated by adrenal CT-scan. MIBG scintigraphy, determination of urinary VMA, metanephrines and total catecholamine levels, measurement of nyctohemeral plasma adrenaline or noradrenaline concentrations (every 2 h during 24 h) and clonidine suppression test. Four of the 25 patients had evidence of adrenal medullary disease in view of the coexistence of CT-scan, MIBG scintigraphy and plasma adrenaline abnormalities. Moderate adrenal enlargement (unilateral, n = 3; bilateral, n = 1) was observed on scans together with a high adrenal MIBG uptake (bilateral, n = 4). Among the urinary parameters studied, a minor MN increase was observed in only one of the four patients. Plasma adrenaline levels were significantly (P less than 0.01) different from those of the other 21 patients (mean + SD 115 + 110 pmol/l). This plasma adrenaline increase is reproducible and not suppressed by clonidine. Unilateral adrenalectomy performed in one patient confirmed a phaeochromocytoma and induced normalization of plasma adrenaline levels. In contrast, the plasma noradrenaline levels of the four patients were not statistically different from those of the other 21 patients. These data suggest that persistent high plasma adrenaline levels may be selectively increased in MTC patients together with a moderate adrenal CT-scan enlargement and a high adrenal MIBG uptake, despite a normal urinary excretion of total catecholamines and catecholamines metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1991

Effects of pertussis toxin on the erythropoietin-stimulated proliferation and differentiation of erythroid-responsive cells.

Erythropoietin (Ep) stimulates the proliferation and differentiation of erythroid progenitor cells. We have investigated the possibility that guanyl nucleotide regulatory (G) proteins may be involved in Ep signal transduction. Pertussis toxin (PT) was found to inhibit Ep-stimulated [3H]-thymidine incorporation and large erythroid colony formation in a dose-dependent fashion, but had no effect on small colony formation or on Ep-induced differentiation. PT specifically adenosine diphosphate-ribosylated a major protein with an apparent molecular mass of 41 kD in erythroid progenitor cell membranes. These findings indicate that the transduction of the Ep signal for proliferation could be mediated in the early steps by a PT-sensitive G protein.

Animals↗
PubMed1990

Cyclic AMP regulation of Gs protein. Thyrotropin and forskolin increase the quantity of stimulatory guanine nucleotide-binding proteins in cultured thyroid follicles.

This study was carried out to clarify the way in which thyrotropin (TSH) and forskolin regulate the adenylylcyclase complex in thyroid follicle cells. We examined the effects of chronic treatment of pig thyroid follicles with TSH or forskolin on the state of G proteins by (a) assaying adenylylcyclase activity, (b) analyzing the ADP-ribosylation of stimulatory G protein (Gs) by cholera toxin, and (c) quantifying the Gs subunits by Western blotting with antipeptide antibodies. Chronic exposure (18 h) of thyroid follicles to a low concentration of TSH (0.01-0.1 milliunit/ml) enhanced the subsequent response of adenylylcyclase to TSH. Higher concentration of TSH (1 milliunit/ml) induced a homologous desensitization of this response. In cells pretreated with forskolin, the TSH-stimulated adenylylcyclase activity was higher than in control cells. The forskolin-or guanosine 5'-(beta, gamma-imido) triphosphate (Gpp(NH)p)-stimulated adenylylcyclase activity was always significantly increased after chronic treatment of cells with TSH or forskolin. Treatment of cultured thyroid follicle membranes with [32P]NAD and cholera toxin resulted in labeling of the Gs alpha (45-52-kDa) component. Culturing follicles with TSH (0.001-1 milliunit/ml) or forskolin (0.01-10 microM) greatly affected the cholera toxin-mediated ADP-ribosylation of the Gs alpha subunit. Gs alpha labeling increased progressively to level off at 1 milliunit/ml TSH or 1 microM forskolin (150-200%). Gs alpha immunoreactivity was increased in parallel (200-300%). The immunoreactivity of G beta subunits in cells cultured with TSH or forskolin was also increased compared with control cells. Cycloheximide abolished the effects of TSH and forskolin on the follicles, suggesting that new protein synthesis is required. These results indicate that Gs protein subunits are up-regulated by TSH and forskolin and suggest that their synthesis in thyroid cells is mediated, at least in part, by a cyclic AMP-dependent mechanism.

Adenosine Diphosphate Ribose↗
PubMed1989

[Value of determining dexamethasone in the rapid adrenal suppression test].

During the dexamethasone suppression test (DST), we evaluated the relationship between the 8 a.m. dexamethasone (DXM) level and the pharmacokinetics of this corticoid after the oral administration of a single dose at midnight of DXM (1 mg) in 7 healthy subjects. The half-life time of the terminal phase for DXM was 283 min +/- 132 min (mean +/- s.d.). The 8 a.m. DXM level, which is positively correlated with the DXM half-life time, is useful for the interpretation of the DST. On the other hand, no correlation was observed between the 8 a.m. plasma cortisol and DXM levels in 21 healthy subjects. However, the negative correlation between the dose of DXM/kg and post-DXM cortisol level suggests the possibility of adjusting the dose of DXM in obese patients.

Administration, Oral↗
PubMedDate not supplied

[Fractionated stereotactic radiotherapy: results in hypophyseal adenomas, acoustic neurinomas, and meningiomas of the cavernous sinus].

PURPOSE: In order to optimize cerebral benign tumor irradiation, fractionated stereotactic radiotherapy allows a focused-volume irradiation (2.1 cm3, 16 mm diameter) under standard fractionation conditions. Results of a retrospective and multicentric analysis are presented. PATIENTS AND METHODS: Fractionated stereotactic radiotherapy uses the ballistic principles of the radiosurgery: stereotactic localization, multi-beam irradiation, secondary collimation, three-dimensional dosimetry. Standard fractionation is possible with a re-locatable non-invasive stereotactic device. The technique has been used for treating pituitary adenomas (86 patients), acoustic neuromas (32 patients) and cavernous meningiomas (26 patients). RESULTS: 1) pituitary adenomas: cumulative tumoral objective-response rates (42 patients) were respectively 42%, 69% and 88% at 24, 48 and 60 months. The cumulative endocrinologic objective-response rates (32 patients) were respectively 53%, 75% and 85% at 24, 48 and 60 months. The cumulative risk of radio-induced hormonal deficiency varied from 18% (growth hormone [GH]) to 42% for TSH (thyroid stimulating hormone) at 48 months. No other complication was observed; 2) acoustic neuromas: 33 tumors, < 25 mm in diameter, were treated in 32 patients. Tumor control was observed in 29/33 tumors: 14 were stable, 15 decreased and three progressed. Useful hearing was maintained in 9/10 patients. Only three patients (9%) presented persistent complications; 3) cavernous meningioma: 17/19 clinical responses were noted, 20 tumoral stabilisations, one partial response and one progression (22 magnetic resonance imaging [MRI] evaluable patients). One unilateral radio-induced blindness was observed. CONCLUSION: For these benign tumors, the focused target volume obtained by the fractionated stereotactic radiotherapy seems to be better adapted to the treatment of limited benign tumors than standard radiotherapy. The use of standard fractionation reduces the risk of severe normal tissue damage, sometimes observed for radiosurgery and inherent in the use of single fraction.

Adenoma↗