Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The triterpenes, alpha-amyrin (AA) and its palmitate (AAP) and linoleate esters (AAL), were tested on models of inflammatory and destructive arthritic processes and their effects were compared with the clinical antiarthritic drugs indomethacin (IN) and methotrexate (MTX). The triterpenes had no effect on the prostaglandin phase of carrageenin pedal edema in rats, which was reduced 28% by 100 microM IN. AAL caused a considerable reduction in the synthesis by human neutrophils of 5-lipoxygenase products--5-HETE (IC50 = 70 microM), LTB4, (62 microM), isomer I (30 microM) and isomer II (24 microM). Rat osteosarcoma cell growth was inhibited by all triterpenes with IC50's (microM) of < 10 (AAP), 14 (AA) and 27 (AAL) and were more effective than IN (35). MTX caused 100% inhibition at a concentration of 10 microM compared with 64% inhibition by AAP. Tadpole collagenase digestion of type I (bone) native collagen was completely inhibited by all the triterpenes as well as IN and MTX at 100 microM. The results indicate that the principal point of antiarthritic intervention by amyrin triterpenes lies in their local inhibition of joint destruction.
Res Commun Mol Pathol Pharmacol 1994 Jul
PMID:Antiarthritic mechanisms of amyrin triterpenes. 795 94

Lymphedema is characterized by chronic swelling of any body part caused by malfunctioning or obstruction in the lymphatic system. Primary lymphedema is often considered genetic in origin. VEGFC, which is a gene encoding the ligand for the vascular endothelial growth factor receptor 3 (VEGFR3/FLT4) and important for lymph vessel development during lymphangiogenesis, has been associated with a specific subtype of primary lymphedema. Through Sanger sequencing of a proband with bilateral congenital pedal edema resembling Milroy disease, we identified a novel mutation (NM_005429.2; c.361+5G>A) in VEGFC. The mutation induced skipping of exon 2 of VEGFC resulting in a frameshift and the introduction of a premature stop codon (p.Ala50ValfsTer18). The mutation leads to a loss of the entire VEGF-homology domain and the C-terminus. Expression of this Vegfc variant in the zebrafish floorplate showed that the splice-site variant significantly reduces the biological activity of the protein. Our findings confirm that the splice-site variant, c.361+5G>A, causes the primary lymphedema phenotype in the proband. We examine the mutations and clinical phenotypes of the previously reported cases to review the current knowledge in this area.
Int J Mol Sci 2018 Aug 01
PMID:A Novel Splice-Site Mutation in VEGFC Is Associated with Congenital Primary Lymphoedema of Gordon. 3007 73