Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017536 (giardiasis)
 1,714 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study was made of 20 rats infested by Giardia muris in which a histologic study was made of the liver, as well as of 25 patients with giardiasis and elevated alanine-aminotransferase levels. Patients with positive A or B hepatitis markers, cholelithiasis or history of drug or alcohol use were excluded. Tests of liver function and liver biopsy were performed and antiparasite therapy was given during three months of follow-up, after which the liver biopsy was repeated. Humoral alterations were compared to those of 30 patients with acute viral hepatitis (15 type A and 15 type B) over the same periods of time. In 20% of the rats, nonspecific liver lesions were found. In the patients liver enzymes and the thymol test normalized a month after treatment and serum bile acids became normal in the third month. The liver biopsy demonstrated hepatic damage in 94% of the patients (in 20 cases cell lesions and in 12 cases inflammatory lesions) which regressed in the third month, the follow-up biopsy being normal after eradication of the parasite was confirmed. The comparative study with viral hepatitis showed highly significant differences in all the variables studied during the follow-up stage. Emphasis is placed on the importance of this lesion and its differential diagnosis to prevent its progression to chronic liver disease.
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PMID:[Acute hepatic lesion caused by Giardia lamblia]. 233 80

Some aaRSs (aminoacyl-tRNA synthetases) develop editing mechanisms to correct mis-charged tRNA. The CP1 (connective peptide 1) domain of LeuRS (leucyl-tRNA synthetase) contains the editing active site, which is the proven target for the broad-spectrum drug AN2690 (5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole). The ESI (eukarya-specific insertion 1) in the CP1 domain of GlLeuRS (Giardia lamblia LeuRS) has been identified. Similar substitution with the ESI from HsLeuRS (Homo sapiens LeuRS) impeded the leucine activation, aminoacylation and post-transfer editing of the enzyme, but had no effect on the editing specificity toward non-specific amino acids. Thr341 in GlLeuRS served as a specificity discriminator, as found in other LeuRS systems, although its substitution with an alanine residue did not destroy Leu-tRNALeu synthesis in vitro and in vivo. The Arg338 was crucial for tRNALeu charging and the Asp440 was crucial for leucine activation and aminoacylation. The post-transfer editing required the CTD (C-terminal domain), Arg338 and Asp440 of GlLeuRS. Interestingly, GlLeuRS was completely resistant to the AN2690, which is an inhibitor of various LeuRSs. The universally conserved aspartate residue in the LeuRS CP1 domains was responsible for the resistance of GlLeuRS and another recently reported AN2690-resistant AaLeuRS (Aquifex aeolicus LeuRS). Our results indicate the functional divergence of some absolutely conserved sites, improve the understanding of the editing function of eukaryotic/archaeal LeuRSs and shed light on the development of a GlLeuRS-specific inhibitor for the treatment of giardiasis.
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PMID:Post-transfer editing by a eukaryotic leucyl-tRNA synthetase resistant to the broad-spectrum drug AN2690. 2055 93