Increase of weight-bearing capacity of patients with lesions of the TFCC using a wrist brace

Study design: Retrospective cross-sectional case series. Background: Lesions of the triangular fibrocartilage complex (TFCC) can result in pain during axial load and unstable distal radioulnar joint (DRUJ). Conventional wrist orthoses decrease initial pain sufficiently but also prevent any movement during recovery and do not contribute to the stabilization of the DRUJ. Purpose: In this retrospective analysis, we tested if the weight-bearing capacity of patients with lesions of the triangular fibrocartilage complex was increased by wearing a brace that stabilizes the distal radioulnar joint. Methods: Twenty-three patients had an arthroscopically confirmed TFCC lesion. We compared preoperative dynamic weight-bearing capacity of both hands with and without a commercially available wrist brace (WristWidget). Subgroup analysis was performed for stability of the distal radioulnar joint and etiology of the TFCC lesion. The dynamic ulnar variance was measured in a modified weight bearing test. We used parametric tests for normally distributed values. Results: The weight-bearing capacity of the hand with TFCC lesion was significantly lower than of the control hand (16 verus 36 kg; p <0.001). The relative load of the affected hand compared to the unaffected hand increased from 48 % (CI 37-60, SD 27) to 59 % (CI 47-72, SD 29 with a brace. The device had no effect on the control hand. Twelve patients with unstable DRUJ had a lower weight-bearing capacity compared to the eleven with stable joint. The percentage improvement with bracing was higher for those with unstable joints (versus stable) and traumatic lesions (versus degenrative). Conclusion: The use of a wrist brace significantly increases the weight-bearing capacity and therefore the maximum tolerated axial load of patients with a lesion of the TFCC. Patients with traumatic lesion or unstable DRUJ tend to show lower values than with degenerative lesions or stable joints

Overexpression of α(1,3)-fucosyltransferase VII is sufficient for the acquisition of lung colonization phenotype in human lung adenocarcinoma HAL-24Luc cells

Metastatic human lung adenocarcinoma HAL-8Luc cells display an enhanced expression of alpha(1,3)-fucosyltransferases (alpha(1,3)-Fuc-Ts) compared with their non-metastatic counterpart HAL-24Luc cells. This correlates with an increased surface expression of Lewis(x) (Le(x))- and Lewis(a) (Le(a))-related molecules and an in vitro enhanced adhesive capacity to E-selectin-expressing endothelial cells (Martin-Satué et al (1998). Cancer Res 58: 1544-1550). In the present work we have stably transfected HAL-24Luc cells with the cDNAs for the alpha(1,3)-Fuc-TIV and VII enzymes and analysed by flow cytometry the expression of Le(x), sialyl-Le(x), sialyl-Le(x) dimeric, Le(a) and sialyl-Le(a). Fuc-TVII transfectants exclusively overexpress sialyl-Le(x) while Fuc-TIV-transfected cells only overexpress the Le(x) oligosaccharide. We show that solely Fuc-TVII transfectants are able to adhere to interleukin-1beta-stimulated HUVEC monolayers. We also demonstrate that Fuc-TVII overexpression in HAL-24Luc cells is sufficient for the acquisition of the lung colonization phenotype. This is the first report directly showing the contribution of an alpha(1,3)-Fuc-T to the metastatic behaviour of human lung adenocarcinoma cells

Genomic structure and alterations of homeobox gene CDX2 in colorectal carcinomas

Expression of CDX2, a caudal-related homeobox gene, was found to be decreased in colorectal carcinomas. Heterozygous null mutant mice as to Cdx2 develop multiple intestinal adenomatous polyps. To clarify the role of CDX2 in colorectal carcinogenesis, we determined its genomic structure, and searched for mutations of CDX2 in 49 sporadic colorectal carcinomas and ten hereditary non-polyposis colorectal cancers (HNPCC) without microsatellite instability. None of them exhibited a mutation. We further examined 19 HNPCC carcinomas with microsatellite instability for mutations in a (G)7 repeat site within CDX2. One of them (5.3%) exhibited one G insertion. Loss of heterozygosity was observed in 2 of the 20 (10%) informative sporadic carcinomas, and in one of the three (33.3%) informative HNPCC cancers. These data indicate that CDX2 may play only a minor role in colorectal carcinogenesis. © 1999 Cancer Research Campaig

Hypermethylation of multiple genes as clonal markers in multicentric hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is highly malignant and prone to multicentric occurrence. Differentiation between a true relapse of HCC and a second primary tumour appearing is of clinical importance. At this point, no convenient method is available to determine the origin of these HCCs. Tissue samples were obtained from 19 patients and analysed for the promoter hypermethylation status of multiple tumour suppressor genes (p16, DAP-Kinase, MGMT, GSTP1, APC, RIZ1, SFRP1, SFRP2, SFRP5, RUNX3, and SOCS1) using methylation-specific PCR (MSP). Methylation status was used to determine tumour clonality. In each of the 19 cases, at least one tumour was recognised as having an aberrantly methylated gene. The frequency of the methylation in tumour tissue was 57.1% in p16, 2.4% in DAP-kinase, 23.8% in GSTP1, 90.5% in APC, 45.2% in RIZ1, 64.3% in SFRP1, 59.5% in SFRP2, 28.6% in SFRP5, 47.6% in RUNX3, and 54.8% in SOCS1, while in MGMT, no aberrant methylation was detected. The methylation status of these genes was assessed using MSP as being either positive or negative, and was used to determine the tumour clonality. The clonality of every tumour could be decided even with lesions that could not be judged by clinical diagnosis or by another molecular method (mt DNA mutation). Determining the methylation status of multiple genes in multicentric HCC was useful as a clonal marker and provided useful information for characterising the tumour. From our findings, multicentric HCCs tend to occur more independently than metastatically from the original tumour. Expanded study should be pursued further for a better understanding of the molecular mechanism of hepatocarcinogenesis

The Isolation of Nucleic Acids from Fixed, Paraffin-Embedded Tissues–Which Methods Are Useful When?

Museums and pathology collections around the world represent an archive of genetic material to study populations and diseases. For preservation purposes, a large portion of these collections has been fixed in formalin-containing solutions, a treatment that results in cross-linking of biomolecules. Cross-linking not only complicates isolation of nucleic acid but also introduces polymerase “blocks” during PCR. A wide variety of methods exists for the recovery of DNA and RNA from archival tissues, and although a number of previous studies have qualitatively compared the relative merits of the different techniques, very few have undertaken wide scale quantitative comparisons. To help address this issue, we have undertaken a study that investigates the quality of nucleic acids recovered from a test panel of fixed specimens that have been manipulated following a number of the published protocols. These include methods of pre-treating the samples prior to extraction, extraction and nucleic acid purification methods themselves, and a post-extraction enzymatic repair technique. We find that although many of the published methods have distinct positive effects on some characteristics of the nucleic acids, the benefits often come at a cost. In addition, a number of the previously published techniques appear to have no effect at all. Our findings recommend that the extraction methodology adopted should be chosen carefully. Here we provide a quick reference table that can be used to determine appropriate protocols for particular aims

Influence of folate status on genomic DNA methylation in colonic mucosa of subjects without colorectal adenoma or cancer

DNA hypomethylation may increase the risk of colorectal cancer. The main aim of this study was to assess the influence of folate status (serum and erythrocyte folate and plasma homocysteine concentrations) on DNA methylation. Methylenetetrahydrofolate reductase (MTHFR 677C → T and 1298A → C), methionine synthase (MS 2756A → G) and cystathionine synthase (CBS 844ins68) polymorphisms were measured to account for potential confounding effects on folate status and DNA methylation. A total of 68 subjects (33 men and 35 women, 36–78 years) free from colorectal polyps or cancer were recruited in a cross-sectional study. Tissue biopsies were obtained at colonoscopy for the determination of DNA methylation in colonic mucosa using an in vitro radiolabelled methyl acceptance assay. Serum and erythrocyte folate were inversely correlated with plasma homocysteine (r=−0.573, P<0.001 and r=−0.307, P=0.01 respectively) and DNA hypomethylation in colonic mucosa (r=−0.311, P=0.01 and r=−0.356, P=0.03). After adjusting for gender, age, body mass index, smoking and genotype, there were weak negative associations between serum and erythrocyte folate and colonic DNA hypomethylation (P=0.07 and P=0.08, respectively)