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Depletion of Muscle Mitochondrial DNA in AIDS Patients with Zidovudine-Induced Myopathy
Lancet 337:508-510, Arnaudo,E.,et al, 1991
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Article Abstract
Long-term ziduvudine therapy in patients with human immunodeficiency virus (HIV)infection can cause a destructive mitochondrial myopathy with histological features of ragged-red fibres(RRF)and proliferation of abnormal mitochondria.In 9 zidovudine-treated patients with this myopathy we found severely reduced amounts(up to 78%reduction vs normal adult controls)of mitochondrial DNA(mtDNA)in muscle biopsy specimens by means of Southern blotting.In 2 HIV-positive patients who had not received zidovudine,muscle mtDNA content did not differ from that in the 4 controls.Depletion of mtDNA seems to be reversible,since 1 patient showed a substantial reduction in RRF and a concomitant pronounced increase in muscle mtDNA content after zidovudine therapy was discontinued.Depletion of muscle mtDNA is probably due to zidovudine-induced inhibition of mtDNA replication by DNA polymerase gamma and is not a secondary effect of HIV infection.
 
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acquired immunodeficiency syndrome
azidodeoxythymidine
mitochondrial disease
molecular genetics
myopathy
myopathy,drug-induced
myopathy,mitochondrial

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