Gyrate atrophy of the choroid and retina

A case of gyrate atrophy of choroid and retina is presented. The serum level of ornithine was 788 mumol/l. The clinical features, the error of metabolism, the inheritance and the treatment of the disease are discussed.     

The p53 codon 72 polymorphism and risk of high-grade cervical intraepithelial neoplasia

BACKGROUND: The Arg/Arg genotype versus Arg/Pro or Pro/Pro at codon 72 of the p53 gene has been implicated in increasing susceptibility of the cervix to human papillomavirus (HPV) infection and thus altering cancer risk. However, research on this topic has been contentious, which prompted us to carry out a case-control study in the Montreal area. METHODS: Cases were women with histologically-confirmed high-grade cervical intraepithelial neoplasia (HGCIN). Controls were women without a history of cervical abnormalities. From each woman, we obtained a cervical specimen for HPV testing and p53 genotyping, and a questionnaire was completed. DNA sequencing was used to minimize genotype misclassification. A subsample of specimens was also genotyped using the TaqMan assay. RESULTS: There were 357 cases and 760 controls recruited between February 2001 and December 2003. The distribution of Arg/Arg, Arg/Pro and Pro/Pro was 55.2, 36.4 and 8.4%, respectively, among cases, and 52.1, 38.7 and 9.2%, among controls, corresponding to an odds ratio (OR) adjusted for ancestral origin of 1.16 (95% confidence interval (CI): 0.9-1.5) for Arg/Arg versus other genotypes. When restricted to high-risk HPV-positive women, the adjusted ORs were 1.40 (CI: 0.9-2.1) and 2.12 (CI: 1.1-4.2), for Arg/Arg versus other genotypes and versus Pro/Pro, respectively. The findings were comparable with analyses of genotype results that agreed between DNA sequencing and TaqMan. CONCLUSIONS: In this study, we attempted to minimize selection bias, population stratification and genotype misclassification. The results suggest that the role of the p53 codon 72 polymorphism on HGCIN is weak at best. Further research may reveal if the polymorphism has a stronger influence on the risk of invasive cervical cancer.     

Absence of FGFR3 mutations in urinary bladder tumours of rats and mice treated with N-butyl-N-(-4-hydroxybutyl)nitrosamine

Frequent activating mutations of FGFR3 (fibroblast growth factor receptor 3) are found in human urothelial cell carcinomas, particularly in superficial papillary tumours (in 74%-84% of pTaG1-G2), but not in carcinomas in situ (CIS) and at a low rate in invasive tumours (in 16%-21% of pT1-4). In mice and rats, BBN (N-butyl-N-(4-hydroxybutyl)nitrosamine) specifically induces bladder tumours. In rats, superficial papillary tumours are mostly observed. In mice, tumour progression follows the CIS pathway: CIS are first observed, followed by tumours that invade surrounding muscle. Therefore, we looked for FGFR3 mutations in these two animal models of bladder cancer. Only the FGFR3b isoform is expressed in human urothelium and derived tumours. We identified the FGFR3b isoform in rats for the first time and showed that this is the main isoform expressed in the bladder urothelium and derived carcinomas in mice and rats, as in humans. SSCP and sequence analysis of FGFR3b showed sequence changes (polymorphisms or silent mutations) in four BBN-induced rat and mouse bladder tumours. The absence of activating mutations of FGFR3 in the mouse model was in agreement with the fact that mouse BBN-induced bladder tumour progression mimics the CIS pathway. The absence of FGFR3 mutations in the rat bladder tumours suggests that, at least at the genetic level, rat superficial papillary tumours differ from their human counterparts.