PubMed · 5719345
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V Mazza, A Brancaccio. 1968. [Adrenal function in welders].. https://pubmed.ncbi.nlm.nih.gov/5719345/
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The human transmembrane fms-like receptor tyrosine kinase Flt-1 is one of the receptors for vascular endothelial growth factor, a growth factor which induces endothelial proliferation and vascular permeability. Flt-1 is expressed specifically in endothelium and is likely to play a role in tumor angiogenesis and embryonic vascularization. To elucidate the molecular basis for the endothelial specific expression of Flt-1, the promoter region has been isolated and functionally characterized. The promoter region contains a TATA box, a GC-rich region, and putative transcription factor binding elements such as cAMP response element binding protein/activating transcription factor (CREB/ATF) and ets. Adenovirus-mediated transient expression of the flt-1 promoter/luciferase fusion gene in endothelial cells and other cell types demonstrated that a 1-kilobase fragment of the 5'-flanking region of flt-1 is involved in the endothelial-specific expression. A CREB/ATF element was found to be essential for basal transcription of the flt-1 expression. In addition, we also showed that the first intron negatively regulates flt-1 promoter activity. The flt-1 promoter will be useful in functional studies on the regulation of endothelial-specific gene expression and also as a tool in targeting the expression of exogenously introduced genes to the endothelium.
Around half of all humans with essential hypertension are resistant to salt (blood pressure does not change by more than 5 mm Hg when salt intake is high), and although various inbred strains of rats display salt-insensitive elevated blood pressure, a gene defect to account for the phenotype has not been described. Atrial natriuretic peptide (ANP) is released from the heart in response to atrial stretch and is thought to mediate its natriuretic and vaso-relaxant effects through the guanylyl cyclase-A receptor (GC-A). Here we report that disruption of the GC-A gene results in chronic elevations of blood pressure in mice on a normal salt diet. Unexpectedly, the blood pressure remains elevated and unchanged in response to either minimal or high salt diets. Aldosterone and ANP concentrations are not affected by the genotype. Therefore, mutations in the GC-A gene could explain some salt-resistant forms of essential hypertension and, coupled with previous work, further suggest that the GC-A signaling pathway dominates at the level of peripheral resistance, where it can operate independently of ANP.
OBJECTIVE: To determine normal adrenal gland size by means of ultrasonography in dogs and to determine the value of ultrasonography in the diagnosis of pituitary-dependent hyperadrenocorticism (PDH) in dogs. DESIGN: Prospective observational study. ANIMALS: 62 dogs: 20 healthy dogs, 20 dogs with non-endocrine disease, and 22 dogs with untreated PDH. PROCEDURE: Length and maximum and minimum diameter of the adrenal glands were measured ultrasonographically. Multiple regression and correlation analyses were used to determine whether body weight, kidney length, aortic diameter, or age was related to adrenal gland size. Two-tailed t-tests and multiple linear regression analysis were used to compare values between groups. Sensitivity and specificity of using ultrasonographic measurement of adrenal gland size as a diagnostic test for PDH were determined. RESULTS: There was a significant linear relationship between adrenal gland length, but not maximum and minimum diameters, and body weight, aortic diameter, and kidney length in healthy dogs and in dogs with nonendocrine diseases. Length, maximum diameter, and minimum diameter of the right adrenal gland and maximum and minimum diameters of the left adrenal gland were significantly greater in dogs with PDH than in healthy dogs and dogs with nonendocrine diseases. As a diagnostic test for PDH, ultrasonographic measurement of maximum or minimum diameter of the left adrenal gland gave the best combination of sensitivity and specificity. For maximum diameter of the left adrenal gland, sensitivity was 77% and specificity was 80%. For minimum diameter of the left adrenal gland, sensitivity was 73% and specificity was 85%. CLINICAL IMPLICATION: Ultrasonography of the adrenal glands is a valuable diagnostic procedure in dogs suspected of having pituitary-dependent hyperadrenocorticism.