No abstract

The relation between responses to survey questions on noise annoyance and self-reported sleep disturbance has been analysed to gain insight in its dependency on noise source or noise type and on individual characteristics. The results show a high correlation between responses (scores 0–10) with Pearson’s correlation coefficient close to 0.8 for respondents who report hearing the source. At the same level of annoyance, scooters and neighbours are associated with more sleep disturbance, air and road traffic with less. The relation between Annoyance (A) and Sleep Disturbance (SD) is also significantly related to age, the use of sleeping drugs, and living alone. However, the differences in the A-SD relations with respect to source and characteristic are small. Noise-related sleep disturbance is associated more strongly to noise annoyance than it is to noise exposure. For transportation noise both scores are more often equal when the annoyance score is 7 or higher; this change in scoring behaviour could be an indication for a change to severe annoyance.

Genetic lack of interleukin 12 receptor β1 (IL-12Rβ1) surface expression predisposes to severe infections by poorly pathogenic mycobacteria or Salmonella and causes strongly decreased, but not completely abrogated, interferon (IFN)-γ production. To study IL-12Rβ1–independent residual IFN-γ production, we have generated mycobacterium–specific T cell clones (TCCs) from IL-12Rβ1–deficient individuals. All TCCs displayed a T helper type 1 phenotype and the majority responded to IL-12 by increased IFN-γ production and proliferative responses upon activation. This response to IL-12 could be further augmented by exogenous IL-18. IL-12Rβ2 was found to be normally expressed in the absence of IL-12Rβ1, and could be upregulated by IFN-α. Expression of IL-12Rβ2 alone, however, was insufficient to induce signal transducer and activator of transcription (Stat)4 activation in response to IL-12, whereas IFN-α/IFN-αR ligation resulted in Stat4 activation in both control and IL-12Rβ1–deficient cells. IL-12 failed to upregulate cell surface expression of IL-18R, integrin α6, and IL-12Rβ2 on IL-12Rβ1–deficient cells, whereas this was normal on control cells. IL-12–induced IFN-γ production in IL-12Rβ1–deficient T cells could be inhibited by the p38 mitogen-activated protein kinase (MAP) kinase inhibitor SB203580 and the MAP kinase kinase (MEK) 1/2 inhibitor U0126, suggesting involvement of MAP kinases in this alternative, Stat4-independent, IL-12 signaling pathway.Collectively, these results indicate that IL-12 acts as a partial agonist in the absence of IL-12Rβ1. Moreover, the results reveal the presence of a novel IL-12Rβ1/Stat4–independent pathway of IL-12 responsiveness in activated human T cells involving MAP kinases. This pathway is likely to play a role in the residual type 1 immunity in IL-12Rβ1 deficiency.

The DD genotype identifies dialysis patients at an increased risk for mortality.