Biomedical subjects

R Mortensen

Publications and source records attributed to R Mortensen.

18 recordsLinked to original sources

PubMed1996

Aldosterone-producing adenomas do not contain glucocorticoid-remediable aldosteronism chimeric gene duplications.

In glucocorticoid-remediable aldosteronism (GRA) a chimeric gene has been described with the activity of aldosterone synthase, but the promoter of 11 beta-hydroxylase leading to ectopic expression of aldosterone synthase activity in the zona fasciculata. Similar to GRA, in aldosterone-producing adenomas (APA), the primary regulation of aldosterone production is ACTH, and there is increased production of the 18-oxygenated cortisol compounds, 18-oxocortisol and 18-hydroxycortisol. Because of these hormonal similarities, we tested whether a chimeric GRA-like gene was present in APA from 11 patients. A GRA-like chimeric gene was not found in the DNA from these tumors and, therefore, is not the mechanism responsible for hyperaldosteronism in APA.

Adenoma↗

PubMed1994

Regulation of alpha o expression by the 5'-flanking region of the alpha o gene.

Many responses of cells to external signals require activation of the heterotrimeric G proteins. These responses depend on the type and amount of G proteins that are expressed. Each cell has a characteristic complement of G protein subunits. For example, the alpha o subunit is very abundant in neural tissues. Very little is known about the mechanisms that determine cellular levels of G proteins. In the present study, we have isolated a genomic clone for mouse alpha o gene and identified the promoter region. There are multiple transcription initiation sites located about 750 base pairs upstream of the translational start site. The promoter region is GC-rich and contains neither a TATA-box nor a CAAT box. Transient expression assays using a series of constructs containing various lengths of the 5'-flanking region of the alpha o promoter demonstrated that the region 300-700 base pairs upstream of the transcription initiation sites is responsible for the basic promoter activity. The relative activity of alpha o promoter is 8-12-fold higher in cells expressing alpha o than in cells lacking alpha o. The level of alpha o in cells may also be regulated at the level of protein translation because deletions in the 5'-noncoding region of alpha o gene increase reporter enzyme expression without a corresponding increase in reporter enzyme mRNA level. Our results suggest that both transcriptional and post-transcriptional mechanisms are involved in regulating the expression of alpha o in vivo. Transcriptional regulation probably is important for control of tissue-specific expression, while posttranscriptional mechanisms may be used to regulate the alpha o level in cells.

Animals↗

PubMed1994

Cryptogenic organizing pneumonia: increased expression of interleukin-8 and fibronectin genes by alveolar macrophages.

Cryptogenic organizing pneumonia (COP) is a fibrotic process that primarily involves the alveolar spaces, alveolar ducts, and small conducting airways. The pathogenesis is not understood. Recent histopathologic studies have shown that during the cellular phase of COP, fibronectin deposits are present in the lung. Moreover, a neutrophil alveolitis is frequently seen in COP. Little is known about the involvement of alveolar macrophages in the pathogenesis of COP. However, alveolar macrophages are the principal resident cells in the airways, and they are thought to play a central role in the fibrotic process by virtue of their ability to express and release cytokines such as interleukin-8 (IL-8; a neutrophil chemotactic factor) and fibronectin (FN; a fibrogenic matrix-associated protein). We have quantified the spontaneous gene expression of IL-8 and FN by alveolar macrophages from five nonsmoking individuals with COP and compared them with 10 normal, healthy volunteers (five smokers, five nonsmokers). Expression of IL-8 and FN was measured by a quantitative assay employing reverse transcription of mRNA and the polymerase chain reaction. beta-actin mRNA expression was quantified as an internal standard, and the expression of FN and IL-8 transcripts was calculated as a ratio with beta-actin. The mean +/- SEM of the IL-8/beta-actin ratio in alveolar macrophages from patients with COP was 0.45 +/- 0.07, which was significantly higher than the level from either normal smokers (0.19 +/- 0.02, P = 0.008) or normal nonsmokers (0.16 +/- 0.01, P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993