Search PubMed⌕ Search

Biomedical subjects

M Stowasser

Publications and source records attributed to M Stowasser.

63 records · Page 4Linked to original sources
PubMedDate not supplied

PCR-SSCP analysis of the angiotensin II type 1 receptor gene in patients with aldosterone-producing adenomas.

1. In patients with primary aldosteronism due to angiotensin-responsive and angiotensin-unresponsive aldosterone-producing adenomas, no differences in the coding region of the angiotensin II type 1 (AT1) receptor gene were observed compared to normal subjects in peripheral blood leucocyte DNA. 2. Furthermore, no differences in the AT1 receptor gene were observed in DNA extracted from tumour tissue of either subgroup. 3. Genotypic and allelic frequencies for an RFLP detected in the coding region of the AT1 receptor gene were not significantly different between normal subjects and patients with aldosterone-producing adenomas as a group, nor between normal subjects and patients of either subgroup when compared with each other. 4. In those patients heterozygous in peripheral blood at the RFLP site, tumour DNA showed the same allelic pattern. 5. In patients with aldosterone-producing adenomas either responsive or unresponsive to the renin-angiotensin system, no differences were detected using SSCP analysis in the coding region of the AT1 receptor gene in peripheral blood or tumour tissue.

Adenoma↗
PubMedDate not supplied

Plasma aldosterone response to ACTH in subtypes of primary aldosteronism.

1. Aldosterone responsiveness to ACTH was compared in eleven patients with angiotensin-unresponsive (AII-U) aldosterone-producing adenomas (APA), 16 with AII-responsive (AII-R) APA and 19 with bilateral adrenal hyperplasia (BAH). 2. After overnight recumbency, aldosterone levels were highest in AII-U APA and lowest in BAH. Following 2 h of upright posture, however, levels were similar among the three groups. 3. During ACTH infusion, aldosterone levels in AII-U and AII-R APA were similar, and higher than those in BAH. Because of the higher basal level, the percentage rise in aldosterone was lower in AII-U APA compared with the other groups, as was the ratio of per cent aldosterone rise to per cent cortisol rise. 4. Slightly but significantly reduced plasma cortisol levels observed in the AII-R APA group may reflect secretion by AII-R APA of a cortisol-like substance that is capable of suppressing ACTH and thus adrenal cortisol production. 5. The tendency of aldosterone to follow the diurnal rhythm of ACTH in AII-U APA may thus represent an unmasking of the normal ability of ACTH to regulate aldosterone, secondary to the loss of AII responsiveness, rather than an enhancement of ACTH effect.

Adenoma↗
PubMedDate not supplied

Analysis of the renin gene in patients with aldosterone-producing adenomas by polymerase chain reaction-single stranded conformational polymorphisms and long polymerase chain reaction.

1. Angiotensin-responsive aldosterone-producing adenomas (AII-R-APA) have increased expression of renin mRNA compared with angiotensin-unresponsive aldosterone-producing adenomas (AII-U-APA) or normal adrenals. 2. Further, significant associations between the BglI, TaqI and HinfI RFLP and aldosterone responsiveness to the renin-angiotensin system of the two subgroups of patients have been reported. 3. Using the polymerase chain reaction based technique single stranded conformational polymorphism, we detected no alterations in exon 1 of the renin gene in peripheral blood leucocyte DNA from normal AII-U-APA and AII-R-APA subjects. 4. Using long-PCR, we amplified a fragment of the renin gene consisting of a region covering 500 bp upstream of exon 1, exon 1 and intron A. No gross changes in this area of the renin gene were found in the three groups of subjects studied. However this does not exclude small alterations in this area.

Adenoma↗
PubMedDate not supplied

Laparoscopic adrenalectomy for adrenal tumours causing hypertension and for 'incidentalomas' of the adrenal on computerized tomography scanning.

1. In a 19 month period from June 1993 to December 1994, 60 patients (mean age 54.8 +/- 1.5 years s.e.m.; 32 males, 28 females) underwent unilateral laparoscopic adrenalectomy by one of us (JCR) for the treatment of hypertension due to primary aldosteronism (n = 48), phaeochromocytoma (n = 3) and cortisol-producing adenoma (n = 1) or to remove adrenal massess incidentally discovered on abdominal computerized tomography scanning ('incidentaloma') performed for other reasons (seven adenomas without biochemical evidence of excessive steroid hormone or catecholamine secretion and one carcinoma autonomously producing cortisol). 2. Compared with conventional open procedures, laparoscopic adrenalectomy was associated with reduced recovery time and a low complication rate (one pulmonary embolus and one port site incisional hernia). 3. Operation time with experience approximates that of open procedures (60 min), but is significantly longer in obese than in non-obese patients, and in males than in females. 4. Patients with adrenal causes of hypertension were cured or significantly improved by laparoscopic unilateral adrenalectomy. 5. Because of our concern regarding malignant potential of incidentalomas and high patient acceptance of laparoscopic techniques, we have reduced our size criteria for removal of incidentalomas.

Adenoma↗
PubMedDate not supplied

PCR-SSCP analysis of the p53 gene in tumours of the adrenal gland.

1. Mutations of the p53 tumour suppressor gene are relatively common in the aetiology of a wide spectrum of tumour types, both sporadic and familial. 2. The majority of mutations of the p53 gene are reported to be in the highly conserved region of exons 5-8. 3. Alterations in exons 4, 5 and 7 of the p53 gene in patients with functional adrenal tumours, including aldosterone-producing adenomas, have recently been described. 4. In the present study PCR-SSCP was used to examine the exons 4-9 of the p53 gene in paired peripheral blood leucocyte and tumour DNA in a variety of adrenal tumours, including aldosterone-producing carcinoma and adenoma (both familial and sporadic), phaeochromocytoma and incidentaloma. 5. No evidence was found for mutations in exons 4-9 of the p53 gene in these varieties of adrenal tumours.

Adrenal Gland Neoplasms↗
PubMedDate not supplied

PCR-SSCP analysis of the promoter region of the renin gene in patients with aldosterone-producing adenomas.

1. Aldosterone-producing adenomas (APA) of the adrenal gland may be responsive or un-responsive to the renin-angiotensin system. 2. We have described increased expression of renin mRNA in angiotensin-responsive aldosterone-producing adenomas (AII-R-APA) compared with angiotensin-un-responsive aldosterone-producing adenomas (AII-U-APA) and significantly different allelic frequencies of the BglI, TaqI and HinfI restriction fragment length polymorphisms of the renin gene between the two groups. 3. An area including the 5' flanking region -500 bp from exon 1, exon 1 and intron A contained no gross insertions or deletions when studied by a long polymerase chain reaction technique. 4. In the present study, polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP) revealed no single base pair alteration in the proximal promoter region (-600 bp to transcription start) of the renin gene in patients with APA (either AII-U-APA or AII-R-APA) when compared with normal subjects. 5. Therefore, mutations in this regulatory region do not appear to explain the different levels of renin gene expression observed in these two subtypes of APA.

Adenoma↗
PubMedDate not supplied

Production of 18-oxo-cortisol in subtypes of primary aldosteronism.

1. In familial hyperaldosteronism type I (FH-I), expression of an adrenocorticotropic hormone (ACTH)-dependent hybrid 11 beta-hydroxylase/aldosterone synthase gene causes excessive 'hybrid steroid' (18-hydroxy- and 18-oxo-cortisol) production. In order to study the mechanism of elevated 'hybrid steroid' levels in angiotensin-unresponsive (AII-U) aldosterone-producing adenoma (APA), we compared responses of 24 h urinary 18-oxo-cortisol, aldosterone and cortisol to dexamethasone (0.5 mg q6h for 4 days) in 11 FH-I patients, 11 patients with AII-U APA, 11 patients with AII-responsive (AII-R) APA and 10 patients with bilateral adrenal hyperplasia (BAH). 2. Consistent, marked suppression (by at least 60%) of 18-oxo-cortisol levels by dexamethasone was seen in all groups except AII-U APA. Aldosterone levels were consistently suppressed to undetectable levels only in FH-I. Cortisol levels were suppressed to undetectable levels in all patients except two with AII-U APA. 3. Production of both 18-oxo-cortisol and aldosterone (and occasionally cortisol) in AII-U APA appears relatively ACTH-independent, consistent with a common mechanism involved in the formation of these two steroids from their respective precursors, which differs from that in FH-I. 4. In AII-R APA and BAH, 18-oxo-cortisol production appears markedly ACTH-dependent, but aldosterone production is not.

Adenoma↗
PubMedDate not supplied

Different allelic patterns at chromosome 11q13 in paired aldosterone-producing tumours and blood DNA.

1. We previously reported loss of heterozygosity (LOH) at region q13 of chromosome 11 in five aldosterone-producing tumours (APT) using restriction fragment length polymorphism (RFLP) analysis, including two from patients with familial hyperaldosteronism. 2. In the present study, microsatellite markers were used to examine 33 informative paired blood and tumour DNA samples from patients with APT for LOH at three loci that map to chromosome 11q13. 3. LOH at one or more loci was detected in seven (21.2%) tumour DNA samples. 4. This study provides further support that mutations at 11q13 may be involved in the underlying pathophysiology of aldosterone-producing tumours of the adrenal cortex.

Adrenal Cortex Neoplasms↗