Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sequence analysis of the 3' end of the 16S rRNA gene of mitochondrial DNA (mtDNA) revealed a single base change G----A, at position 3010. This mutation was first identified in a patient who had recovered from chloramphenicol-induced aplastic anaemia (CAP-induced AA). A link between this mutation and CAP-induced AA was ruled out by investigating three other similar patients, none of whom had the mutation. This mutation lies within or near the chloramphenicol binding site in a part of the 16S rRNA gene which shows high evolutionary conservation and where polymorphisms have not been previously reported. Hybridization tests with appropriate oligonucleotide probes in 114 individuals reveal that this mutation has a polymorphic frequency of about 14% in Europeans.
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PMID:A new genetic polymorphism in the 16S ribosomal RNA gene of human mitochondrial DNA. 262 28

The case reports presented so far, concerning a possible causative relationship between the ophthalmological use of chloramphenicol (O-CAP) and blood dyscrasias, are few in number, not always fully documented and therefore not always convincing. The overall use of this drug in a restricted area in the Netherlands was assessed. On a yearly basis 1:29 people used O-CAP. In a four-year period in the same area, 12 patients with aplastic anemia and 190 patients with other cytopenic dyscrasias were found. After exclusion of all cases with other possible causes of the dyscrasia, e.g. cancer and related therapy, other drugs than O-CAP and infectious diseases, 59 cases remained in which a definite cause could not be established. We traced back the use of O-CAP in the relevant period. No dyscrasias were found that unequivocally were caused by O-CAP. The rate of O-CAP use in the dyscrasia-group was approximately equal to that in the population as a whole. Hence we concluded that it is highly improbable that O-CAP played a part in the etiology of blood dyscrasias in the region. Statistical evaluation of material derived from a much larger region may, however, lead to a more differentiated conclusion.
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PMID:Blood dyscrasias and topically applied chloramphenicol in ophthalmology. 358 4

A comparative study of the cellular transport of CAP and its nitroso derivative (NO-CAP) was carried out in Raji cells, a transformed human lymphoblastoid cell line. Both agents were concentrated by the cells by a factor of 3 (cellular/extracellular concentration ratio). The cellular uptake of NO-CAP, like that of CAP, was found to be rapid and temperature-independent. Thus the greater cytotoxicity of NO-CAP is apparently not due to an enhanced uptake of the nitroso derivative relative to CAP. In contrast to the similarity of uptake, NO-CAP becomes covalently bound to both Raji cells and freshly isolated human bone marrow cells to a much higher extent (15-fold). Also, cells previously loaded with CAP or NO-CAP retain three times as much of the nitroso compound during a 24 hr dialysis against a drug-free isotonic solution. The increased binding of NO-CAP to human hematopoietic cells attests to the greater reactivity of the p-substituted aromatic nitroso group and is consistent with the postulate that reduction products of the nitro group of CAP may be responsible for CAP-induced aplastic anemia.
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PMID:The cellular uptake and covalent binding of nitroso-chloramphenicol. 726 36

We compared the effects of CAP and its nitroso derivative on DNA synthesis, CFU-C growth, and cell viability in human bone marrow and on mouse CFU-S viability in vitro. As previously reported from this laboratory, CAP inhibited DNA synthesis only when used in high concentrations (greater than 3 x 10(-4)M), and the inhibition was largely reversible. It also caused a reversible concentration-dependent inhibition of CFU-C growth but did not affect marrow cell viability. In sharp contrast, nitroso-CAP inhibited DNA synthesis in much lower concentrations and caused irreversible inhibition of CFU-C growth and cell death at 5 x 10(-5)M as well as irreversible mouse CFU-S damage. In a rapidly growing human lymphoid cell line, nitroso-CAP caused accumulation of cells in the G2M phase and increasing cell death within the arrested population. We have postulated from these and other observations that CAP-induced aplastic anemia occurs in the predisposed host who provides the milieu for the transformation of the p-NO2 group of the drug to toxic intermediates.
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PMID:Nitroso-chloramphenicol: possible mediator in chloramphenicol-induced aplastic anemia. 739 56