The DEK oncoprotein and its emerging roles in gene regulation.

The DEK oncogene is highly expressed in cells from most human tissues and overexpressed in a large and growing number of cancers. It also fuses with the NUP214 gene to form the DEK-NUP214 fusion gene in a subset of acute myeloid leukemia. Originally characterized as a member of this translocation, DEK has since been implicated in epigenetic and transcriptional regulation, but its role in these processes is still elusive and intriguingly complex. Similarly multifaceted is its contribution to cellular transformation, affecting multiple cellular processes such as self-renewal, proliferation, differentiation, senescence and apoptosis. Recently, the roles of the DEK and DEK-NUP214 proteins have been elucidated by global analysis of DNA binding and gene expression, as well as multiple functional studies. This review outlines recent advances in the understanding of the basic functions of the DEK protein and its role in leukemogenesis.

A major population of mucosal memory CD4+ T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality.

Mucosal tissues contain large numbers of memory CD4(+) T cells that, through T-cell receptor-dependent interactions with antigen-presenting cells, are believed to have a key role in barrier defense and maintenance of tissue integrity. Here we identify a major subset of memory CD4(+) T cells at barrier surfaces that coexpress interleukin-18 receptor alpha (IL-18Rα) and death receptor-3 (DR3), and display innate lymphocyte functionality. The cytokines IL-15 or the DR3 ligand tumor necrosis factor (TNF)-like cytokine 1A (TL1a) induced memory IL-18Rα(+)DR3(+)CD4(+) T cells to produce interferon-γ, TNF-α, IL-6, IL-5, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-22 in the presence of IL-12/IL-18. TL1a synergized with IL-15 to enhance this response, while suppressing IL-15-induced IL-10 production. TL1a- and IL-15-mediated cytokine induction required the presence of IL-18, whereas induction of IL-5, IL-13, GM-CSF, and IL-22 was IL-12 independent. IL-18Rα(+)DR3(+)CD4(+) T cells with similar functionality were present in human skin, nasal polyps, and, in particular, the intestine, where in chronic inflammation they localized with IL-18-producing cells in lymphoid aggregates. Collectively, these results suggest that human memory IL-18Rα(+)DR3(+) CD4(+) T cells may contribute to antigen-independent innate responses at barrier surfaces.

Behavioural and cognitive behavioural therapy for obsessive compulsive disorder in children and adolescents.

BACKGROUND: While behavioural or cognitive-behavioural therapy (BT/CBT) is recommended as the psychotherapeutic treatment of choice for children and adolescents with obsessive-compulsive disorder (OCD), the application of BT/CBT to paediatric OCD may not be straightforward. OBJECTIVES: This review examines the overall efficacy of BT/CBT for paediatric OCD, its relative efficacy against psychopharmacology and whether there are benefits in using BT/CBT combined with medication. SEARCH STRATEGY: We searched CCDANCTR-Studies and CCDANCTR-References (searched on 5/8/2005), MEDLINE, EMBASE, PsycINFO, the reference lists of all selected studies and handsearched journals specifically related to behavioural treatment of OCD. SELECTION CRITERIA: Included studies were randomised controlled trials or quasi-randomised trials with participants who were 18 years of age or younger and had a diagnosis of OCD, established by clinical assessment or standardised diagnostic interview. Reviewed studies included the standard behavioural or cognitive-behavioural techniques, either alone or in combination, compared with wait-list or pill placebo. DATA COLLECTION AND ANALYSIS: The quality of selected studies was assessed by two independent reviewers. The primary outcomes comprised of endpoint scores on the gold standard clinical outcome measure of OCD symptoms, distress and interference (CY-BOCS) and endpoint OCD status. MAIN RESULTS: Four studies with 222 participants were considered eligible for inclusion and for data extraction. Two studies showed significantly better post-treatment functioning and reduced risk of continuing with OCD at post-treatment for the BT/CBT group compared to placebo or wait-list comparisons. We suggested that the POTS 2004 result, equal to a difference of about eight points on the CY-BOCS, represented the best available estimate for the efficacy of BT/CBT relative to no treatment. (WMD -7.50; 95% CI -11.55, -3.45). Pooled evidence from two trials indicated that the efficacy of BT/CBT and medication did not differ significantly (WMD -3.87; 95% CI -8.15, 0.41). There was evidence of the benefit of combined BT/CBT and medication compared to medication alone (WMD -4.55; 95% CI -7.40, -1.70), but not relative to BT/CBT alone (WMD -2.80; 95% CI -7.55, 1.95). The rates of drop out suggested BT/CBT is an acceptable treatment to child and adolescent patients and their families. AUTHORS' CONCLUSIONS: Although only based on a small number of studies, behavioural or cognitive-behaviour therapy appears to be a promising treatment for OCD in children and adolescents. It can lead to better outcomes when combined with medication compared to medication alone. Additional trials are needed to confirm these findings. In the interim, consideration should be given to the ways in which BT/CBT might be made more widely available as a treatment for OCD in children and adolescents.