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X Bertagna

Publications and source records attributed to X Bertagna.

143 records · Page 8Linked to original sources

[Recent data on the group of melanotropic and lipotropic pituitary hormones (MSH-LPH) and on the brain morphinomimetic peptides (endorphins)].

It was admitted that human beta-MSH was responsible for the hyper-pigmentation observed in some syndromes associated with ACTH hypersecretion. beta-LPH was a pituitary polypeptide, containing the entire sequence of beta-MSH in its fragment 37-58, and the physiological role of which remained unknown. alpha-MSH and CLIP (Corticotrophin-like Intermediary Peptide) were thought to be specific of certain species possessing a distinct pituitary pars intermedia. Recent data give new insight upon some of these conceptions. beta-MSH seems not to exist in man; it is almost established now that plasma "Immunoreactive beta-MSH" (IR-beta-MSH) is in fact beta- and/or gamma-LPH. In chronic renal failure plasma IR-beta-MSH is elevated because of a decreased plasma disappearance rate, whereas ACTH is normal. Good evidence suggests that both LPH and ACTH are synthesized in the same pituitary cell within a common polypeptidic precursor. Endogenous peptides with morphinomimetic activity (Endorphins) have been isolated from brain and hypophysis; they are all made up of different fractions of beta-LPH-C-terminal fragment 61-91; It is likely that they represent a new class of brain neurotransmitters involved in some functions of the central nervous system, structural similarities suggest that beta-LPH may be the biosynthetic precursor of Endorphins, however such a hypothesis remains to be clearly demonstrated.

Adrenocorticotropic Hormone↗

[Secretion of a beta lipotropine type substances by a corticomelanotropic adenoma in Nelson's syndrome (author's transl)].

Using radioimmunoassay of human melanotropic hormone (beta-MSH), were studied in one female patient with Nelson's syndrome the properties of the immunoreactive beta-MSH (beta-MSH-IR) secreted in the circulation in vitro by a pituitary adenoma. With Sephadex G-50 gel, beta-MSH-IR of plasma or from a culture mediium is eluted in greater part in a volume corresponding to a molecular weight of some 6,000 to 10,000. In the radioimmunological systems employed, the dilution curve of beta-MSH-IR in a culture medium is not parallel to that of synthetic human beta-MSH; by contrast, it is parallel to that a lipotropine, purified human beta-LPH.

Adenoma↗

Dynamics and characterization of plasma immunoreactive beta-melanocyte stimulating hormone in hemodialysis patients: its relationship to ACTH.

We studied the plasma immunoreactive beta-MSH ("beta-MSH") in hemodialysis patients to determine its basal level, plasma disappearance rate, gel filtration and immunological characteristics. All patients had increased plasma "beta-MSH" (90--440 pg/ml; normal less than 90 pg/ml). Plasma ACTH and cortisol values were within the normal range. Cortisol infusion over 2 h induced almost no plasma "beta-MSH" variation as compared to controls where "beta-MSH" decreased rapidly (apparent half-life 90 min.); more prolonged administration of corticosteroids (dexamethasone 0.5 mg every 6 h for two days) caused a slight (20%) but significant (P less than 0.001) decrease of "beta-MSH." On Sephadex G-50 endogenous "beta-MSH" eluted in a molecular weight range of 6,000--10,000. In our radioimmunoassay dilution curves of endogenous "beta-MSH" paralleled that of synthetic human beta-MSH, but not that of purified human beta-LPH. In conclusion, hemodialysis patients show a clear dissociation between elevated "beta-MSH" and normal ACTH plasma levels. "beta-MSH" probably has a decreased plasma disappearance rate and seems related to a substance different from human beta-MSH.

Adrenocorticotropic Hormone↗

Rapid identification of patients with essential hypertension sensitive to acebutolol (a new cardioselective beta-blocker).

Acebutolol, a new cardioselective beta-blocking agent, was administered for 48 hours to 44 patients with essential hypertension at a total dosage of 2.0 g (2,000 mg). The slowing down of their pulse rate and the decrease in blood pressure were highly significant, whereas eight subjects treated with placebos had no change in either the pulse rate or blood pressure. Plasma renin activity decreased from 2.26 +/- 2.11 ng/ml/hour to 0.87 +/- 1.04 ng/ml/hour. The decrease in blood pressure was correlated with the initial plasma renin activity and with the decrease in plasma renin activity. These results demonstrate that a rapid decrease in blood pressure can be obtained in patients with essential hypertension treated with acebutolol and that the decrease in blood pressure is related to the initial state of the renin-angiotensin system.

Acebutolol↗

Microsequencing evidence for the maturation of human proopiomelanocortin into an 18 amino acid beta-melanocyte stimulating hormone [h beta MSH(5-22)] in nonpituitary tissue.

Sixty pmoles of a material with molecular size, immunological, and RP-HPLC characteristics identical to that of h beta MSH(5-22) were purified from a bronchial carcinoid tumor responsible for the ectopic ACTH syndrome. The first 16 cycles of microsequencing revealed the following sequence: Asp-Glu-Gly-Pro-Tyr-Arg-Met-Glu-X-Phe-Arg-Trp-Gly-X-Pro- Pro-, identical to the first 16 amino acids of h beta MSH(5-22). Since this material was recognized by an antibody which requires the free COOH-terminal Asp22 residue, it can be assumed that it is indeed h beta MSH(5-22). We also show that neither the 5 N acetic acid nor the 1 N HCl extraction procedure artefactually generated h beta MSH-like material in normal or tumoral human pituitaries and in nonpituitary tumors. We conclude that h beta MSH(5-22) is a normal maturation product of proopiomelanocortin in the human nonpituitary tissues which express its gene, including the hypothalamus and ACTH-secreting tumors.

Amino Acid Sequence↗

Vasopressin receptors modulate the pharmacological phenotypes of Cushing's syndrome.

We have examined the expression profiles of the different vasopressin receptors (V1, V2, V3) that can be expressed in the three different types of tumors associated with Cushing's syndrome. V3 (V1b) receptor cDNA was cloned from a pituitary tumor responsible for Cushing's disease. We show that it is overexpressed in these tumors and can respond to DD-AVP. High expression of the V3 receptor on highly differentiated, ACTH-secreting, bronchial carcinoid tumors explain why these non-pituitary tumors occasionally respond to vasopressin, mimicking a "pituitary-like" behavior. A retrospective analysis showed that vasopressin induced an ACTH-independent cortisol rise in 27% of the adrenocortical tumors responsible for Cushing's syndrome. V1 mRNA was detected in normal adrenal cortex and in all tumors. Adenomas had significantly higher levels than carcinomas. V1 mRNA levels were higher in responders than in non-responders. One adenoma which had a brisk cortisol response in vivo, also had in vitro cortisol responses that were inhibited by a specific V1 antagonist. In situ hybridization showed the presence of V1 mRNA in the normal human adrenal cortex where the signal predominated in the compact cells of the zona reticularis. A positive signal was also present in the tumors with high V1 mRNA levels determined by RT-PCR; its distribution pattern was heterogeneous and showed preferential association with compact cells. High-and not ectopic-expression of the V1 receptor occurs in a minority of adrenal cortical tumors which become directly responsive to vasopressin stimulation.

Adrenal Cortex Neoplasms↗

ACTH receptor mRNA in human adrenocortical tumors: overexpression in aldosteronomas.

We previously reported that ACTH receptor (ACTH-R) mRNA is expressed in cortisol-secreting adrenal tumors, with significant differences between adenomas and carcinomas. In order to complete the study we have now evaluated 11 aldosteronomas (APA), 14 non-hypersecreting adenomas, 2 androgen-secreting adenomas and 8 normal adrenal glands. The level of ACTH-R mRNA was evaluated by competitive RT-PCR using a non-homologous competitor. ACTH-R gene was expressed in all tissues. All APA showed highest ACTH-R mRNA levels. Despite signs of individual heterogeneity, the level of ACTH-R transcripts was reduced in carcinomas. Furthermore, no significant differences were observed among cortisol-secreting adenomas, non hypersecreting adenomas and controls. The results show that ACTH-R mRNA is expressed in all adrenocortical tumors. The overexpression of ACTH-R in APA supports the role of ACTH on aldosterone secretion in these tumors, as also suggested by the presence of a diurnal rhythm, the lack of response to Angiotensin II, upright posture and captopril administration. The low abundance of ACTH-R in carcinomas might be a useful molecular marker of malignancy even if some overlap between carcinomas and adenomas does exist.

Adenoma↗

[Cushing's disease. Current data on its course and treatment].

Recent developments in the treatment of Cushing's disease, particularly the trans-sphenoidal microadenomectomy, have prompted a survey of the pathophysiological theories of ACTH hypersecretion in this condition. The results of the trans-sphenoidal approach are reported and the post-surgical evolution (success failure or recurrence) are discussed. It is emphasized that a long fellow up is essential to assess the efficacy of this therapeutic approach.

Adenoma↗

Influence of radiotherapy on long-term relapse in clinically non-secreting pituitary adenomas. A retrospective study (1970-1988).

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.

Adenoma↗

[Magnetic resonance imaging in Cushing disease. Prediction of surgical results].

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.

Adenoma↗