Parental needs among children with birth defects: defining a parent-to-parent support network.

The objective of this study was to explore how a parent-to-parent support network could impact parents of a child with a structural birth defect by specifically looking at parents' continued needs, aspects influencing their participation in support networks, and their recommendations. Structural birth defects occur in approximately 3 % of all infants, representing a significant public health issue. For many reasons, parents are uniquely qualified to provide support to each other. Data were collected retrospectively through a qualitative approach of focus groups or one-on-one interviews. Thirty one parents of infants registered in the Utah Birth Defect Network participated in the study. Three themes emerged, "current sources and inconsistencies in parent-to-parent-support," "aspects that influence participation in parent-to-parent network," and "recommendations for a parent-to-parent program." Health care providers need to be aware of the services and inform parents about these options. A statewide parent-to-parent network integrated into all hospitals would be a valuable resource to facilitate sharing of issues related to caring for an infant or child with a birth defect.

Constitutive SOCS-3 expression protects T-cell lymphoma against growth inhibition by IFNalpha.

Signal transducer and activator of transcription (Stat)3 is constitutively activated in cutaneous T-cell lymphoma (CTCL), where it protects tumour cells against apoptosis. The constitutive activation of Stat3 leads to a constitutive expression of suppressor of cytokine signalling (SOCS)-3. In healthy cells, SOCS-3 is transiently expressed following cytokine stimulation and functions as a negative feedback inhibitor of the Stat3-activating kinases. Here, we attempt to resolve the apparent paradox of a simultaneous SOCS-3 expression and Stat3 activation in the same cells. We show that (i) SOCS-3 expression in tumour cells is equal to or higher than in cytokine-stimulated nonmalignant T cells, (ii) SOCS-3 is not mutated in CTCL, (iii) overexpression of SOCS-3 blocks IFNalpha-mediated growth inhibition without affecting Stat3 activation, growth, and apoptosis, and (iv) inhibition of SOCS-3 by a dominant negative Stat3 (Stat3D) increases the IFNalpha-mediated growth inhibition. Taken together, these data show that SOCS-3 does not inhibit Stat3 activation, growth, and survival in CTCL. In contrast, SOCS3 protects tumour cells against growth inhibition by IFNalpha. Unlike SOCS-1, SOCS-3 is therefore not a tumour suppressor but rather a protector of tumour cells.

Malignant Tregs express low molecular splice forms of FOXP3 in Sézary syndrome.

Sézary syndrome (SS) is an aggressive variant of cutaneous T-cell lymphoma. During disease progression, immunodeficiency develops; however, the underlying molecular and cellular mechanisms are not fully understood. Here, we study the regulatory T cell (Treg) function and the expression of FOXP3 in SS. We demonstrate that malignant T cells in 8 of 15 patients stain positive with an anti-FOXP3 antibody. Western blotting analysis shows expression of two low molecular splice forms of FOXP3, but not of wild-type (wt) FOXP3. The malignant T cells produce interleukin-10 and TGF-beta and suppress the growth of non-malignant T cells. The Treg phenotype and the production of suppressive cytokines are driven by aberrant activation of Jak3 independent of the FOXP3 splice forms. In contrast to wt FOXP3, the low molecular splice forms of FOXP3 have no inhibitory effect on nuclear factor-kappaB (NF-kappaB) activity in reporter assays which is in keeping with a constitutive NF-kappaB activity in the malignant T cells. In conclusion, we show that the malignant T cells express low molecular splice forms of FOXP3 and function as Tregs. Furthermore, we provide evidence that FOXP3 splice forms are functionally different from wt FOXP3 and not involved in the execution of the suppressive function. Thus, this is the first description of FOXP3 splice forms in human disease.