Aims: Ophthalmic pterygium is a potentially vision-threatening lesion of unkn own etiology, related to an exposure to solar light. Mutations to the ras genes are frequently observed in lesions related to an exposure t...Aims: Ophthalmic pterygium is a potentially vision-threatening lesion of unkn own etiology, related to an exposure to solar light. Mutations to the ras genes are frequently observed in lesions related to an exposure to solar light. The pr esent study aims at screening pterygia for mutations at codons 12 and 13 of the ras genes. Methods: In all, 50 pterygia were examined, together with respective blood samples and specimens of normal conjunctiva. A PCR reaction was performed to amplify sequences containing codons 12 and 13 of Ki-ras, H-ras, and N-ras. An RFLP analysis was then performed to detect point mutations at codon 12. The mutational status at codons 12 and 13 was further explored with sequencing of PC R products. Results: RFLP analysis revealed Ki-ras mutations at codon 12 in fiv e (10%) of pterygia, whereas H-ras or N-ras mutations were not observed. Sequ encing confirmed Ki-ras mutations at codon 12 and revealed absence of mutations at codon 13. The presence of Ki-ras mutations was significantly correlated wit h postoperative recurrence (P=0.02) and young age (P=0.04). Mutations were not o bserved in specimens of blood or normal conjunctiva for any of the genes examine d. Conclusions: The absence of Nras mutations is in agreement with previous repo rts concerning mucosal lesions. The detection of Ki-ras mutations and the assoc iation with postoperative recurrence implies a possible role of Ki-ras in the c linical profile of pterygium. The mechanism of Ki-ras mutations is unclear and could be independen t of the action of UV light.展开更多
Background/Aims: To elucidate whether ribavirin acts as a mutagen in the clinical setting and to clarify the relationship between ribavirin-induced mutations and virological response to combined therapy. Methods: Thir...Background/Aims: To elucidate whether ribavirin acts as a mutagen in the clinical setting and to clarify the relationship between ribavirin-induced mutations and virological response to combined therapy. Methods: Thirty-four patients with hepatitis C virus (HCV) genotype 1b received ribavirin monotherapy for 4 weeks, followed by a 24-week course of IFN/ribavirin therapy. HCV mutations during a non-treatment observation period and during subsequent ribavirin monotherapy were determined, and the relationship between mutations and response to subsequent IFN/ribavirin therapy was evaluated. Results: Serum HCV significantly decreased from 6.90 to 6.56 log10copy/ml in response to ribavirin monotherapy (P < 0.0001). Nucleotide mutations in the NS5A and NS5B regions occurred during ribavirin monotherapy at a rate of 2.9× 10- 2/site/year and 1.3× 10- 2/site/year, respectively, a significantly higher rate than the mutation rates during the prior non-treatment observation period (0.60× 10- 2/site/year and 0.24× 10- 2/site/year, P = 0.02, respectively). Mutation rates in the NS5A region were significantly higher in sustained viral responders (SVRs, n = 10) than in non-responders (8.8× 10- 2/site/year vs. 0.38× 10- 2/site/year, P = 0.0005, respectively). In the NS5A region, non-synonymous mutations only occurred in SVRs. Conclusions: Ribavirin may act as a mutagen, and mutations occurring during ribavirin therapy correlate with the virological response to subsequent IFN/ribavirin combination therapy.展开更多
History was taken systematically for 100 azoospermic, nonvasectomized men referred consecutively to a Danish fertility clinic. The men were examined by ultrasound, and their blood samples were analyzed for karyotype, ...History was taken systematically for 100 azoospermic, nonvasectomized men referred consecutively to a Danish fertility clinic. The men were examined by ultrasound, and their blood samples were analyzed for karyotype, Y microdeletions, and cystic fibrosis transmembrane conductance regulator gene mutations. In 29%of patients, the condition could be explained by genetic abnormalities; in 22%, by diseases or external influence; and in 27%, by former cryptorchidism. The azoospermic conditionremained unexplained in only 22%.展开更多
文摘Aims: Ophthalmic pterygium is a potentially vision-threatening lesion of unkn own etiology, related to an exposure to solar light. Mutations to the ras genes are frequently observed in lesions related to an exposure to solar light. The pr esent study aims at screening pterygia for mutations at codons 12 and 13 of the ras genes. Methods: In all, 50 pterygia were examined, together with respective blood samples and specimens of normal conjunctiva. A PCR reaction was performed to amplify sequences containing codons 12 and 13 of Ki-ras, H-ras, and N-ras. An RFLP analysis was then performed to detect point mutations at codon 12. The mutational status at codons 12 and 13 was further explored with sequencing of PC R products. Results: RFLP analysis revealed Ki-ras mutations at codon 12 in fiv e (10%) of pterygia, whereas H-ras or N-ras mutations were not observed. Sequ encing confirmed Ki-ras mutations at codon 12 and revealed absence of mutations at codon 13. The presence of Ki-ras mutations was significantly correlated wit h postoperative recurrence (P=0.02) and young age (P=0.04). Mutations were not o bserved in specimens of blood or normal conjunctiva for any of the genes examine d. Conclusions: The absence of Nras mutations is in agreement with previous repo rts concerning mucosal lesions. The detection of Ki-ras mutations and the assoc iation with postoperative recurrence implies a possible role of Ki-ras in the c linical profile of pterygium. The mechanism of Ki-ras mutations is unclear and could be independen t of the action of UV light.
文摘Background/Aims: To elucidate whether ribavirin acts as a mutagen in the clinical setting and to clarify the relationship between ribavirin-induced mutations and virological response to combined therapy. Methods: Thirty-four patients with hepatitis C virus (HCV) genotype 1b received ribavirin monotherapy for 4 weeks, followed by a 24-week course of IFN/ribavirin therapy. HCV mutations during a non-treatment observation period and during subsequent ribavirin monotherapy were determined, and the relationship between mutations and response to subsequent IFN/ribavirin therapy was evaluated. Results: Serum HCV significantly decreased from 6.90 to 6.56 log10copy/ml in response to ribavirin monotherapy (P < 0.0001). Nucleotide mutations in the NS5A and NS5B regions occurred during ribavirin monotherapy at a rate of 2.9× 10- 2/site/year and 1.3× 10- 2/site/year, respectively, a significantly higher rate than the mutation rates during the prior non-treatment observation period (0.60× 10- 2/site/year and 0.24× 10- 2/site/year, P = 0.02, respectively). Mutation rates in the NS5A region were significantly higher in sustained viral responders (SVRs, n = 10) than in non-responders (8.8× 10- 2/site/year vs. 0.38× 10- 2/site/year, P = 0.0005, respectively). In the NS5A region, non-synonymous mutations only occurred in SVRs. Conclusions: Ribavirin may act as a mutagen, and mutations occurring during ribavirin therapy correlate with the virological response to subsequent IFN/ribavirin combination therapy.
文摘History was taken systematically for 100 azoospermic, nonvasectomized men referred consecutively to a Danish fertility clinic. The men were examined by ultrasound, and their blood samples were analyzed for karyotype, Y microdeletions, and cystic fibrosis transmembrane conductance regulator gene mutations. In 29%of patients, the condition could be explained by genetic abnormalities; in 22%, by diseases or external influence; and in 27%, by former cryptorchidism. The azoospermic conditionremained unexplained in only 22%.
