Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The macula densa in rabbits and rats was studied by transmission electron microscopy (TEM). After different experimental procedures, the kidneys were fixed by direct perfusion with the fixative without prior flushing of the blood. With this technique, the renal cortex is consistently well preserved. The lateral intercellular spaces of all proximal and distal nephron segments were constantly found to be closed, whereas those of the macula densa varied: depending on the functional situation of the kidney, they were found to be either dilated or closed. Dilated intercellular spaces in the macula densa were encountered in control, sodium-rich, and sodium-deficient rabbits and rats and, in addition, in rats with hypotonic and isotonic hypervolemia. In contrast, in rats with hypertonic hypovolemia and in rats undergoing furosemide or mannitol diuresis, the lateral intercellular spaces of the macula densa were closed. Whether these findings reflect the in vivo state of the macula densa interspaces remains uncertain. The association with specific functional stages demonstrates, at least, a specific behavior of the macula densa cells that is different from that of all other proximal and distal nephron segments and appears to be similar to that of the collecting duct epithelium. The findings suggest that the macula densa is a water-permeable cell plaque within the otherwise water-impermeable thick ascending limb.
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PMID:Variability of intercellular spaces between macula densa cells: a transmission electron microscopic study in rabbits and rats. 695 82

Although techniques for cell-specific gene expression via viral transfer have advanced, many challenges (e.g., viral vector design, transduction of genes into specific target cells) still remain. We investigated a novel, simple methodology for using adenovirus transfer to target specific cells of the kidney tubules for the expression of exogenous proteins. We selected genes encoding sodium-dependent phosphate transporter type 2a (NPT2a) in the proximal tubule, sodium-potassium-2-chloride cotransporter (NKCC2) in the thick ascending limb of Henle (TALH), and aquaporin 2 (AQP2) in the collecting duct. The promoters of the three genes were linked to a GFP-coding fragment, the final constructs were then incorporated into an adenovirus vector, and this was then used to generate gene-manipulated viruses. After flushing circulating blood, viruses were directly injected into the renal arteries of rats and were allowed to site-specifically expression in tubule cells, and rats were then euthanized to obtain kidney tissues for immunohistochemistry. Double staining with adenovirus-derived EGFP and endogenous proteins were examined to verify orthotopic expression, i.e. "adenovirus driven NPT2a-EGFP and endogenous NHE3 protein", "adenovirus driven NKCC2-EGFP and endogenous NKCC2 protein" and "adenovirus driven AQP2-EGFP and endogenous AQP2 protein". Owing to a lack of finding good working anti-NPT2a antibody, an antibody against a different protein (sodium-hydrogen exchanger 3 or NHE3) that is also specifically expressed in the proximal tubule was used. Kidney structures were well-preserved, and other organ tissues did not show EGFP staining. Our gene transfer method is easier than using genetically engineered animals, and it confers the advantage of allowing the manipulation of gene transfer after birth. This is the first method to successfully target gene expression to specific cells in the kidney tubules. This study may serve as the first step for safe and effective gene therapy in the kidney tubule diseases.
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PMID:Targeting gene expression to specific cells of kidney tubules in vivo, using adenoviral promoter fragments. 2825 1