Autoimmune lymphoproliferative syndrome in a patient with a new minimal deletion in the death domain of the FAS gene

We present a case of autoimmune lymphoproliferative syndrome (ALPS) caused by a previously undescribed minimal deletion in the death domain of the FAS gene. ALPS is an uncommon disease associated with an impaired Fas-mediated apoptosis. The patient presented with a history of splenomegaly since 4 months of age, associated with cervical lymphadenopathy, which improved with oral corticosteroid treatment. Relevant laboratory findings were the presence of anemia, thrombocytopenia, and positive direct and indirect Coombs tests. He was not an offspring of consanguineous parents. Two cervical lymph node biopsies were performed, at 4 years and at 6 years of age. In both lymph nodes, there was marked paracortical expansion by lymphocytes in variable stages of immunoblastic transformation and a very high cell proliferating index. Some clear cells were also present, raising the suspicion of malignant lymphoma. In one of the lymph nodes, there was also a focus rich in large histiocytes with round nuclei and emperipolesis, consistent with focal Rosai-Dorfman disease. Immunostaining showed numerous CD3+ cells, many of which were double-negative (CD4- CD8-) and expressed CD57, especially around the follicles. Molecular studies of the lymph node biopsy showed a point deletion (4-base pair deletion) in exon 9 of the FAS gene (930del TGCT), which results in 3 missense amino acids. (c) 2008 Elsevier Inc. All rights reserved.

European 1: A globally important clonal complex of Mycobacterium bovis

We have identified a globally important clonal complex of Mycobacterium bovis by deletion analysis of over one thousand strains from over 30 countries. We initially show that over 99% of the strains of M. bovis, the cause of bovine tuberculosis, isolated from cattle in the Republic of Ireland and the UK are closely related and are members of a single clonal complex marked by the deletion of chromosomal region RDEu1 and we named this clonal complex European 1 (Eu1). Eu1 strains were present at less than 14% of French, Portuguese and Spanish isolates of M. bovis but are rare in other mainland European countries and Iran. However, strains of the Eu1 clonal complex were found at high frequency in former trading partners of the UK (USA, South Africa, New Zealand, Australia and Canada). The Americas, with the exception of Brazil, are dominated by the Eu1 clonal complex which was at high frequency in Argentina, Chile, Ecuador and Mexico as well as North America. Eu1 was rare or absent in the African countries surveyed except South Africa. A small sample of strains from Taiwan were non-Eu1 but, surprisingly, isolates from Korea and Kazakhstan were members of the Eu1 clonal complex. The simplest explanation for much of the current distribution of the Eu1 clonal complex is that it was spread in infected cattle, such as Herefords, from the UK to former trading partners, although there is evidence of secondary dispersion since. This is the first identification of a globally dispersed clonal complex M. bovis and indicates that much of the current global distribution of this important veterinary pathogen has resulted from relatively recent International trade in cattle. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.

The anti-MMP activity of benzalkonium chloride

Objective: This study evaluated the ability of benzalkonium chloride (BAC) to bind to dentine and to inhibit soluble recombinant MMPs and bound dentine matrix metalloproteinases (MMPs). Methods: Dentine powder was prepared from extracted human molars. Half was left mineralized; the other half was completely demineralized. The binding of BAG to dentine powder was followed by measuring changes in the supernatant concentration using UV spectrometry. The inhibitory effects of BAC on rhMMP-2, -8 and -9 were followed using a commercially available in vitro proteolytic assay. Matrix-bound endogenous MMP-activity was evaluated in completely demineralized beams. Each beam was either dipped into BAG and then dropped into 1 mL of a complete medium (CM) or they were placed in 1 mL of CM containing BAG for 30 days. After 30 days, changes in the dry mass of the beams or in the hydroxyproline (HYP) content of hydrolysates of the media were quantitated as indirect measures of matrix collagen hydrolysis by MMPs. Results: Demineralized dentine powder took up 10-times more BAG than did mineralized powder. Water rinsing removed about 50% of the bound BAC, whilst rinsing with 0.5 M NaCl removed more than 90% of the bound BAG. BAG concentrations 0.5 wt% produced 100% inhibition of soluble recombinant MMP-2, -8 or -9, and inhibited matrix-bound MMPs between 55 and 66% when measured as mass loss or 76-81% when measured as solubilization of collagen peptide fragments. Conclusions: BAC is effective at inhibiting both soluble recombinant MMPs and matrix-bound dentine MMPs in the absence of resins. (C) 2010 Elsevier Ltd. All rights reserved.

Genetic and environmental contributions to educational attainment in Australia

The genetic and environmental contributions to educational attainment in Australia are examined using a multiple regression model drawn from the medical research literature. Data from a large sample of Australian twins are analysed. The findings indicate that at least as much as 50 percent and perhaps as much as 65 percent of the variance in educational attainments can be attributed to genetic endowments. It is suggested that only around 25 percent of the variance in educational attainments may be due to environmental factors, though this contribution is shown to be around 40 percent when adjustments for measurement error and assortative mating are made. The high fraction of the observed variation in educational attainments due to genetic differences is consistent with results reported by Heath et al. (Heath, A.C., Berg, K., Eaves, L.J., Solaas, M.H., Corey, L.A., Sundet, J., Magnus, P., Nance, W.E., 1985. Education policy and the heritability of educational attainment. Nature 314(6013), 734-736.), Tambs et al. (Tambs, K., Sundet, J.M., Magnus, P., Berg, K., 1989. Genetic and environmental contributions to the covariance between occupational status, educational attainment and IQ: a study of twins. Behavior Genetics 19(2), 209-222.), Vogler and Fulker (Vogler, G.P., Fulker, D.W., 1983. Familial resemblance for educational attainment. Behavior Generics 13(4), 341-354.) and Behrman and Taubman (Behrman, J., Taubman, P., 1989. Is schooling mostly in the genes? Nature-nurture decomposition using data on relatives. Journal of Political Economy 97(6), 1425-1446.), suggesting that the finding is robust. (C) 2001 Elsevier Science Ltd. All rights reserved.

CDT, GGT, and AST as markers of alcohol use: The WHO/ISBRA Collaborative Project

Background: Estimates of the performance of carbohydrate deficient transferrin (CDT) and gamma glutamyltransferase (GGT) as markers of alcohol consumption have varied widely. Studies have differed in design and subject characteristics. The WHO/ISBRA Collaborative Study allows assessment and comparison of CDT, GGT, and aspartate aminotransferase (AST) as markers of drinking in a large, well-characterized, multicenter sample. Methods: A total of 1863 subjects were recruited from five countries (Australia, Brazil, Canada, Finland, and Japan). Recruitment was stratified by alcohol use, age, and sex. Demographic characteristics, alcohol consumption, and presence of ICD-10 dependence were recorded using an interview schedule based on the AUDADIS, CDT was assayed using CDTect(TM) and GGT and AST by standard methods. Statistical techniques included receiver operating characteristic (ROC) analysis. Multiple regression was used to measure the impact of factors other than alcohol on test performance. Results: CDT and GGT had comparable performance on ROC analysis, with AST performing slightly less well. CDT was a slightly but significantly better marker of high-risk consumption in men. All were more effective for detection of high-risk rather than intermediate-risk drinking. CDT and GGT levels were influenced by body mass index, sex, age, and smoking status. Conclusions: CDT was little better than GGT in detecting high- or intermediate-risk alcohol consumption in this large, multicenter, predominantly community-based sample. As the two tests are relatively independent of each other, their combination is likely to provide better performance than either test alone, Test interpretation should take account sex, age. and body mass index.