Natural History Of Atopic Disease In Early Childhood: Is Cord Blood IgE A Prognostic Factor?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68008/2/10.1177_000992289203100411.pd

Related subunits of NF-[kappa]B map to two distinct loci associated with translocations in leukemia, NFKB1 and NFKB2

The chromosomal locations of the human genes NFKB1 and NFKB2, which encode two alternative DNA binding subunits of the NF-[kappa]B complex, p105 and p49/p100, respectively, have been determined. p105 was assigned to 4q21.1-q24 and p49/p100 to chromosome 10 by Southern blot analysis of panels of human/Chinese hamster cell hybrids. The locations were confirmed by fluorescence in situ hybridization and mapped with greater resolution to 4q23 and 10q24, respectively. These results demonstrate that these members of the NF-[kappa]B family are unlinked. Interestingly, p49/p100 as well as p105 maps to regions associated with certain types of acute lymphoblastic leukemia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30009/1/0000377.pd

Syndromic neurodevelopmental disorder associated with de novo variants in DDX23

International audienceThe DEAD/DEAH box RNA helicases are a superfamily of proteins involved in the processing and transportation of RNA within the cell. A growing literature supports this family of proteins as contributing to various types of human disorders from neurodevelopmental disorders to syndromes with multiple congenital anomalies. This article presents a cohort of nine unrelated individuals with de novo missense alterations in DDX23 (Dead-Box Helicase 23). The gene is ubiquitously expressed and functions in RNA splicing, maintenance of genome stability, and the sensing of double-stranded RNA. Our cohort of patients, gathered through GeneMatcher, exhibited features including tone abnormalities, global developmental delay, facia

Molecular mechanisms of sulfasalazine-induced T-cell apoptosis

1. Impaired apoptosis of T-lymphocytes is involved in the development of chronic inflammatory disorders. Previously we have shown that the anti-inflammatory drug sulfasalazine induces apoptosis in a murine T-lymphocyte cell line. The aims of the present study were to expand these observations to human systems and to analyse the molecular basis for sulfasalazine-induced apoptosis. 2. Sulfasalazine induces apoptosis both in Jurkat cells, a human T-leukaemia cell line (ED(50) value ∼1.0 mM), and in primary human peripheral blood T-lymphocytes (ED(50) value ∼0.5 mM). In contrast SW620 colon carcinoma cells or primary human synoviocytes are not affected at these concentrations suggesting a cell type-specific sensitivity to sulfasalazine. 3. Sulfasalazine triggers the mitochondrial accumulation of Bax and induces a collapse of the mitochondrial transmembrane potential (ΔΨ(m)). 4. Sulfasalazine causes cytochrome c release from mitochondria and subsequent activation of caspase-3 and downstream substrates. However, the pan-caspase inhibitor Z-VAD.fmk fails to inhibit sulfasalazine-induced apoptosis. 5. Sulfasalazine stimulates mitochondrio-nuclear translocation of the novel apoptogenic factor apoptosis-inducing factor (AIF) and triggers large-scale DNA fragmentation, a characteristic feature of AIF-mediated apoptosis. 6. Sulfasalazine-induced ΔΨ(m) loss, AIF redistribution, and cell death are fully prevented by overexpression of Bcl-2. 7. In conclusion, our data suggest that sulfasalazine-induced apoptosis of T-lymphocytes is mediated by mitochondrio-nuclear translocation of AIF and occurs in a caspase-independent fashion. Sulfasalazine-induced apoptosis by AIF and subsequent clearance of T-lymphocytes might thus provide the molecular basis for the beneficial therapeutic effects of sulfasalazine in the treatment of chronic inflammatory diseases