Aspergillus nidulans is a non-pathogenic fungus with well-developed genetics which provides an excellent model system for studying different aspects of drug resistance in filamentous fungi. As a preliminary step to characterizing genes that confer pleiotropic drug resistance in Aspergillus, we isolated cycloheximide-sensitive mutants of A. nidulans, which is normally resistant to this drug. The rationale for this approach is to identify genes whose products are important for drug resistance by analysing mutations that alter the resistance/sensitivity status of the cell. Fifteen cycloheximide-sensitive (named scy for sensitive to cycloheximide) mutants of A. nidulans were isolated and genetically characterised. Each scy mutant was crossed with the wild-type strain and five of the crosses gave 50% cycloheximide-sensitive progeny suggesting that they carry a single mutation required for cycloheximide sensitivity. We examined ten scy mutants for resistance/sensitivity to other drugs or stress agents with different and/or the same mechanism of action. Six of these mutants exhibited other altered resistance/sensitivity phenotypes which were linked to the cycloheximide sensitivity. These six mutants were analyzed by pairwise crosses and found to represent six linkage groups, named scyA-F. One of the mutants showed fragmentation of its vacuolar system and, in addition, its growth was osmotic, low-pH, and oxidative-stress sensitive.
The oral adsorbent AST-120 is one type of activated carbon for oral use. In the present study, AST-120 was administered, to clarify its effect, on surgically induced hepatic failure in dogs and rats. Portacaval shunts and varying extents of hepatectomies were performed on 44 dogs. Eleven dogs were given an ordinary diet (control group), and 33 dogs received the oral adsorbent with an ordinary diet after the operation (AST group). Plasma bile acids and ammonia increased, and body weight decreased in both groups. However, after the administration of AST-120, the plasma bile acids and ammonia decreased significantly, and the body weight tended to increase in the AST group. Portacaval shunts and about 70 per cent hepatectomy were performed on 59 Sprague-Dawley rats. These rats were divided into two groups, diet with the oral adsorbent (AST group, n = 19) and an ordinary diet alone (control group, n = 40). DNA synthesis and protein synthesis of the liver were measured on the 5th, 10th and 20th postoperative days using radioisotopes in these rats. Both DNA and protein synthesis of the liver were increased significantly in the AST group. Histological examination revealed many more glycogen granules in the cytoplasm of hepatocytes in the AST group compared to the control group on the 5th postoperative day. It was suggested that some metabolic toxin was adsorbed by AST-120 in the alimentary tract.
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