Biomedical subjects

D Vieau

Publications and source records attributed to D Vieau.

23 records · Page 2Linked to original sources

PubMed1991

The secretory granule peptides 7B2 and CCB are sensitive biochemical markers of neuro-endocrine bronchial tumours in man.

OBJECTIVE: Bronchial tumours are the most frequent cause of the ectopic ACTH syndrome. Two types of tumours are classically responsible: the relatively benign carcinoids and the highly aggressive small cell carcinomas. Both have neuro-endocrine features and are thought to originate from the endocrine component of the bronchial tree. Our objective was to assess the sensitivity of 7B2 and secretogranin 1 as new biochemical markers of neuro-endocrine differentiation in these tumours in comparison with gastrin releasing peptide. METHODS: Tissue concentration of 7B2, secretogranin 1 fragments (GAWK and CCB), gastrin releasing peptide and beta-endorphin were measured in normal human lung (n = 4), bronchial carcinoid tumours with (n = 5) and without (n = 15) the ectopic ACTH syndrome, small cell carcinomas (n = 2), squamous cell carcinomas (n = 11) and adenocarcinomas (n = 6). Molecular weight forms of immunoreactive--ACTH, -GAWK, -gastrin releasing peptide, and -7B2 were also examined using gel exclusion chromatography and Western blot analysis. RESULTS: We detected 7B2 immunoreactivity in 19 of 22 neuro-endocrine lung tumours (with values ranging from less than 5 to 555 fmol/mg wet weight tissue), CCB immunoreactivity in 20 of 22 tumours with neuro-endocrine features (with values ranging from less than 5 to 19,875 fmol mg wet weight tissue) and gastrin releasing peptide immunoreactivity in 10 of 22 neuro-endocrine lung tumors (with values ranging from less than 5 to 11,132 fmol/mg wet weight tissue). Immunoreactive 7B2 and CCB were detected neither in tumours with non-endocrine features, nor in the four normal lung specimens. Differing molecular weight forms of immunoreactive 7B2 in two bronchial carcinoids associated with the ectopic ACTH syndrome showed a predominant signal corresponding to a molecular weight of 22 kDa; in addition, a second signal of 19 kDa was also present. The differing molecular weight forms of immunoreactive ACTH related peptides in the five tumours responsible for the ectopic ACTH syndrome showed, in addition to ACTH1-39, the constant presence in variable proportions of corticotrophin-like intermediary lobe peptide (or ACTH18-39). The differing molecular weight forms of immunoreactive GAWK showed heterogeneous results with materials eluting at Kav of 0, 0.3 and 0.4 respectively. In the three bronchial carcinoids studied, two immunoreactive gastrin releasing peptide molecular weight forms were always found at Kav of 0.5 and 0.85 corresponding to gastrin releasing peptide and its fragment 14-27 respectively. CONCLUSION: Our results show that 7B2 and the two fragments of secretogranin 1 (GAWK and CCB) are the best biochemical markers of neuro-endocrine differentiation in human lung tumours.

ACTH Syndrome, Ectopic↗

PubMed1991

Proopiomelanocortin gene expression in normal and tumoral human lung.

Proopiomelanocortin (POMC) gene expression is not restricted to the pituitary corticotroph cell, but also takes place in many normal and tumoral nonpituitary tissues. In contrast, the ectopic ACTH syndrome is a rare event. Because it is most often associated with lung tumors, we specifically studied this tissue, analyzing the different forms of POMC RNAs in normal specimens as well as in various types of tumors. The endocrine nature of the tumors was assessed by both histological examination and measurements of secretogranin-I fragments in the tissue extracts. POMC RNA was first detected by Northern blot analysis; its absolute amounts and its various molecular forms were more precisely quantified and discriminated by S1 mapping studies using a single stranded DNA probe located at the 5' end of exon 3. In five bronchial carcinoid tumors associated with the ectopic ACTH syndrome, a highly predominant, if not single, POMC RNA identical to the 1200-nucleotide (nt) pituitary message was present, the high amounts of which were correlated with those of POMC peptides in the same tissues. In five bronchial carcinoid tumors not associated with the ectopic ACTH syndrome, the same message was detected (four of five), with a second, often predominant, short RNA of about 800 nt (five of five), and the overall amounts of POMC RNAs were low. Similar patterns of POMC RNAs were observed in squamous cell tumors, adenocarcinomas, and normal lung, where the short 800-nt RNA tended to be predominant. These results show that POMC gene expression can be demonstrated in normal lung tissue and in all types of lung tumors. The ectopic ACTH syndrome only occurs with tumors capable of generating high amounts of the pituitary-like message, a phenomenon that seems to be restricted to an occasional tumor with features of neuroendocrine differentiation.

Carcinoid Tumor↗

PubMed1990

A case of pseudo-Nelson's syndrome: cure of ACTH hypersecretion by removal of a bronchial carcinoid tumor responsible for Cushing's syndrome.

It may sometimes be difficult to distinguish Cushing's disease from ectopic ACTH syndrome. A case is described here of a patient with a Cushing's syndrome and diagnostic difficulties. Initial features were consistent with a Cushing's disease (in particular metopirone test was positive). Because of relapse of hypercortisolism after mitotane therapy, total adrenalectomy was performed. Thereafter features occurred that evoked Nelson's syndrome, including high plasma ACTH levels and a pituitary mass syndrome. Pituitary reserve testings by vasopressin or corticotropin-releasing factor were positive, although inconstantly, in that plasma ACTH increased. A lung tumor was discovered about 20 yr after the first clinical signs of hypercortisolism. Its removal led to the discovery of a bronchial carcinoid tumor and was followed by normalization of plasma ACTH levels. An analysis of proopiomelanocortin-related peptides was performed postoperatively on the blood drawn before and after the tumor resection and on the tumor; the results of this study would have been contributive to the diagnosis of occult ectopic ACTH tumor. In conclusion this case demonstrates the limitations of the conventional procedures in the diagnosis of the ectopic ACTH syndrome. At contrast the newer biochemical procedures may be very useful in determining the type of hypercortisolism.

ACTH Syndrome, Ectopic↗

PubMed1990

Pituitary-like proopiomelanocortin transcripts in human Leydig cell tumors.

Proopiomelanocortin is a polypeptide precursor molecule, the processing of which generates ACTH, beta-endorphin, the beta- and gamma-lipotropins, the joining peptide, and the NH2-terminal fragment. Anterior pituitary corticotrophs are the major site of proopiomelanocortin gene expression in man and the predominant, if not sole source of circulating ACTH. Recent data have established that proopiomelanocortin gene expression also occurs in various normal nonpituitary tissues, one of the best studied being the testis. In this latter organ the dominant gene products are short transcripts of approximately 800 nucleotides, which lack the first two exons of the gene and cannot encode a complete proopiomelanocortin molecule. In this report we show that the mode of proopiomelanocortin gene expression is occasionally modified in human Leydig cell tumors: a 1,200-nucleotide mRNA species identical to that in the pituitary is produced. It results from the usual (pituitary) start site of transcription and thus can encode the complete proopiomelanocortin molecule. In two out of six tumors, large amounts of the 1,200-nucleotide transcript led to a dramatic increase of approximately 1,000-fold in proopiomelanocortin peptide concentrations as compared with the normal and peritumoral testis. Proopiomelanocortin processing in these tumors generates various peptide fragments including ACTH. These results may help to understand the mechanism of proopiomelanocortin expression in nonpituitary tumors and have implications for the more general phenomenon of ectopic hormone secretion.

Blotting, Northern↗

PubMed1989

Corticotrophin-like intermediary lobe peptide as a marker of alternate pro-opiomelanocortin processing in ACTH-producing non-pituitary tumours.

In order to evaluate which of human (h) corticotrophin-like intermediary lobe peptide (CLIP) or h beta-melanocyte stimulating hormone5-22 (h beta MSH5-22) was the better marker of alternate pro-opiomelanocortin (POMC) processing, both peptides were simultaneously sought in the same tissue extracts from a normal human pituitary, six corticotrophic adenomas, and four non-pituitary tumours responsible for an ectopic ACTH syndrome. Human CLIP was detected using a combination of gel exclusion chromatography and two different radioimmunoassays (RIAs): a mid-ACTH RIA which recognized ACTH but not CLIP, and a COOH-ACTH RIA which recognized both molecules. Human beta MSH5-22 had been measured previously. Neither hCLIP nor h beta MSH5-22 were detected in the normal or tumoural pituitaries. The four non-pituitary tumours, in contrast, contained both peptides; the hCLIP and h beta MSH5-22 ratios (CLIP/CLIP + ACTH and h beta MSH5-22/h beta MSH5-22 + h gamma LPH) ranged from 40 to 94% and from 24 to 46%, respectively. In a given tissue the hCLIP ratio was always higher than the h beta MSH5-22 ratio. hCLIP is therefore the better marker of alternate POMC processing.

ACTH Syndrome, Ectopic↗