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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although emphysema is generally characterized by damage to pulmonary elastic fibers, the causes of such injury appear to be complex and are not entirely explained by a singular imbalance between elastases and their inhibitors. Other factors could compromise elastic fiber integrity. To test the validity of this argument, hamsters were instilled intratracheally with a nonelastolytic enzyme, hyaluronidase (which reduces lung hexuronic acid content by 21% after 24 h), then exposed to an otherwise nontoxic concentration of oxygen (60%) for 4 days. Additional groups were given (1) hyaluronidase and room air, (2) saline and 60% oxygen, and (3) saline and room air. Treatment with both hyaluronidase and 60% oxygen resulted in a significant increase in air-space enlargement at 4 days (67.1 vs. 57.9 microns for saline/room air controls; p < .05), which was accompanied by only minimal inflammatory changes, as determined by both light microscopy and lavage cytology. Animals receiving either hyaluronidase or 60% oxygen alone showed no significant increases in air-space size compared to those given saline and exposed to room air. While the mechanisms responsible for these results are unclear, the marked increase in radiolabeling of lung elastin cross-links (desmosine and isodesmosine) in animals receiving both hyaluronidase and 60% oxygen (429 vs. 168 cpm/g dry lung for saline/room air controls; p < .05), as well as a significant decrease in total lung desmosine and isodesmosine (32.5 vs. 37.7 micrograms/lung for saline/room air controls; p < .05), suggests that elastic fiber damage is a potential factor. Moreover, only those animals receiving both hyaluronidase and 60% oxygen showed a significant rise in cell-free elastase activity in lavage fluids compared to saline/room air controls (83.3 vs. 48.3 ng; p < .05). On the basis of these findings, it is concluded that while elastic fiber damage may be a common pathway in emphysema, the factors that initiate the disease may be more varied than previously suspected and not always related to the balance between elastases and their inhibitors.
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PMID:Pulmonary air-space enlargement induced by intratracheal instillment of hyaluronidase and concomitant exposure to 60% oxygen. 846 61

Heparan sulfate chains are initially synthesized on core proteins as linear polysaccharides composed of glucuronic acid-N-acetylglucosamine repeating units and subjected to marked structural modification by sulfation at various places and epimerization of hexuronic acid residues (C5-epimerase) at the Golgi lumen and further by 6-O-desulfation at the cell surface, which generates their characteristic divergent fine structures. This chapter focuses on the biological and physiological functions of 6-O-sulfation in HS and the characterization of the enzymes catalyzing 6-O-sulfation (HS6ST). HS6STs in mammals such as humans and mice comprise of three isoforms (HS6ST-1, -2, and -3) and one alternatively spliced form of HS6ST-2 (HS6ST-2S). Each of these isoforms has distinct substrate preferences, albeit overlapping each other. These HS6ST isoforms are expressed in a spatiotemporally regulated manner in most organs. HS6ST-1-deficient mice are lethal mostly at later embryonic stages and exhibit abnormal angiogenesis in labyrinthine zone of placenta and aberrant lung morphology similar to pulmonary emphysema. These knockout mice also exhibit retinal axon guidance abnormality at the optic chiasm. Other HS6ST-deficient animals reveal various malformations in muscle development and branching morphology of the caudal vein of zebrafish, in tracheal formation of Drosophila, and in axon guidance of ventral nerve cord interneurons of Caenorhabditis elegans. Mouse embryonic fibroblasts prepared from HS6ST-1/HS6ST-2 double knockout mice did produce HS lacking 6-O-sulfation and responded differently to various FGFs dependent signaling.
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PMID:Mice deficient in heparan sulfate 6-O-sulfotransferase-1. 2080 42