Anatomical significance of a posterior horn of medial meniscus: the relationship between its radial tear and cartilage degradation of joint surface

<p>Abstract</p> <p>Background</p> <p>Traumatic injury and surgical meniscectomy of a medial meniscus are known to cause subsequent knee osteoarthritis. However, the difference in the prevalence of osteoarthritis caused by the individual type of the medial meniscal tear has not been elucidated. The aim of this study was to investigate what type of tear is predominantly responsible for the degradation of articular cartilage in the medial compartment of knee joints.</p> <p>Methods</p> <p>Five hundred and forty eight cadaveric knees (290 male and 258 female) were registered in this study. The average age of cadavers at death was 78.8 years old (range: 52-103 years). The knees were macroscopically examined and their medial menisci were classified into four groups according to types of tears: "no tear", "radial tear of posterior horn", "other types of tear" and "worn-out meniscus" groups. The severity of cartilage degradation in their medial compartment of knee joints was evaluated using the international cartilage repair society (ICRS) grading system. We statistically compared the ICRS grades among the groups using Mann-Whitney U test.</p> <p>Results</p> <p>The knees were assigned into the four groups: 416 "no tear" knees, 51 "radial tear of posterior horn" knees, 71 "other types of tear" knees, and 10 "worn-out meniscus" knees. The knees with substantial meniscal tears showed the severer ICRS grades of cartilage degradation than those without meniscal tears. In addition, the ICRS grades were significantly severer in the "radial tear of posterior horn" group than in the "other types of tear" group, suggesting that the radial tear of posterior horn in the medial meniscus is one of the risk factors for cartilage degradation of joint surface.</p> <p>Conclusions</p> <p>We have clarified the relationship between the radial tear of posterior horn in the medial meniscus and the severer grade of cartilage degradation. This study indicates that the efforts should be made to restore the anatomical role of the posterior horn in keeping the hoop strain, when patients' physical activity levels are high and the tear pattern is simple enough to be securely sutured.</p

Mutation analysis and characterization of ATR sequence variants in breast cancer cases from high-risk French Canadian breast/ovarian cancer families

BACKGROUND: Ataxia telangiectasia-mutated and Rad3-related (ATR) is a member of the PIK-related family which plays, along with ATM, a central role in cell-cycle regulation. ATR has been shown to phosphorylate several tumor suppressors like BRCA1, CHEK1 and TP53. ATR appears as a good candidate breast cancer susceptibility gene and the current study was designed to screen for ATR germline mutations potentially involved in breast cancer predisposition. METHODS: ATR direct sequencing was performed using a fluorescent method while widely available programs were used for linkage disequilibrium (LD), haplotype analyses, and tagging SNP (tSNP) identification. Expression analyses were carried out using real-time PCR. RESULTS: The complete sequence of all exons and flanking intronic sequences were analyzed in DNA samples from 54 individuals affected with breast cancer from non-BRCA1/2 high-risk French Canadian breast/ovarian families. Although no germline mutation has been identified in the coding region, we identified 41 sequence variants, including 16 coding variants, 3 of which are not reported in public databases. SNP haplotypes were established and tSNPs were identified in 73 healthy unrelated French Canadians, providing a valuable tool for further association studies involving the ATR gene, using large cohorts. Our analyses led to the identification of two novel alternative splice transcripts. In contrast to the transcript generated by an alternative splicing site in the intron 41, the one resulting from a deletion of 121 nucleotides in exon 33 is widely expressed, at significant but relatively low levels, in both normal and tumoral cells including normal breast and ovarian tissue. CONCLUSION: Although no deleterious mutations were identified in the ATR gene, the current study provides an haplotype analysis of the ATR gene polymorphisms, which allowed the identification of a set of SNPs that could be used as tSNPs for large-scale association studies. In addition, our study led to the characterization of a novel Δ33 splice form, which could generate a putative truncated protein lacking several functional domains. Additional studies in large cohorts and other populations will be needed to further evaluate if common and/or rare ATR sequence variants can be associated with a modest or intermediate breast cancer risk