The study confirmed not only that GAD patients show a bias in selective attention to threat, relative to controls, but also that this bias operates for naturalistic, non-verbal stimuli. As the attentional biases for threat and happy faces appeared to develop over a different time frame, different underlying mechanisms may be responsible.

Anxious patients (n = 20) and normal controls (n = 20) carried out a modified Stroop color-naming task with anxiety-and depression-related words in supraliminal and subliminal exposure conditions. Within the anxious group, patients with generalized anxiety disorder (GAD) without concurrent depression (n = 11) showed more color-naming interference for anxiety words than neutral words in comparison with patients with a combined diagnosis of GAD and depression (n = 9). Compared with controls, the GAD subgroup without concurrent depression showed slower color naming for negative than neutral words, in both supraliminal and subliminal conditions, replicating K. Mogg, B. P. Bradley, R. Williams, and A. Mathews's (1993) results. These findings provide further evidence of an anxiety-related bias for negative information in preconscious processes and highlight the importance of assessing concurrent depression.

RationaleAcute respiratory distress syndrome (ARDS) affects over 200 000 people annually in the USA. Despite causing severe, and often refractory, hypoxaemia, the high mortality and long-term morbidity of ARDS results mainly from extra-pulmonary organ failure; however the mechanism for this organ crosstalk has not been determined.MethodsUsing autologous radiolabelled neutrophils we investigated the pulmonary transit of primed and unprimed neutrophils in humans. Flow cytometry of whole blood samples was used to assess transpulmonary neutrophil priming gradients in patients with ARDS, sepsis and perioperative controls.Main resultsUnprimed neutrophils passed through the lungs with a transit time of 14.2 s, only 2.3 s slower than erythrocytes, and with <5% first-pass retention. Over 97% of neutrophils primed ex vivo with granulocyte macrophage colony-stimulating factor were retained on first pass, with 48% still remaining in the lungs at 40 min. Neutrophils exposed to platelet-activating factor were initially retained but subsequently released such that only 14% remained in the lungs at 40 min. Significant transpulmonary gradients of neutrophil CD62L cell surface expression were observed in ARDS compared with perioperative controls and patients with sepsis.ConclusionsWe demonstrated minimal delay and retention of unprimed neutrophils transiting the healthy human pulmonary vasculature, but marked retention of primed neutrophils; these latter cells then ‘deprime’ and are re-released into the systemic circulation. Further, we show that this physiological depriming mechanism may fail in patients with ARDS, resulting in increased numbers of primed neutrophils within the systemic circulation. This identifies a potential mechanism for the remote organ damage observed in patients with ARDS.

The human complement regulator CD55 is a key molecule protecting self-cells from complement-mediated lysis. X-ray diffraction and analytical ultracentrifugation data reveal a rod-like arrangement of four short consensus repeat (SCR) domains in both the crystal and solution. The stalk linking the four SCR domains to the glycosylphosphatidylinositol anchor is extended by the addition of 11 highly charged O-glycans and positions the domains an estimated 177 Å above the membrane. Mutation mapping and hydrophobic potential analysis suggest that the interaction with the convertase, and thus complement regulation, depends on the burial of a hydrophobic patch centered on the linker between SCR domains 2 and 3.CD55 ͉ complement regulator ͉ pathogen receptor ͉ glycoprotein T he complement system is an important component of the immune response, consisting of more than 30 proteins that function together to provide an initial defense against invasion by pathogens. The classical, alternative, and lectin pathways (CP and AP for classical and alternative pathways, respectively), each activated by different stimuli, converge by means of a series of enzyme-linked cascades to target cells for destruction. Regulation to prevent inappropriate activation against self occurs by means of the proteins encoded in the regulators of complement activation gene clusters, which act at key points in the cascades to prevent pathological consequences. Decay-accelerating factor (CD55) is a member of the regulators of complement activation protein family (1), and its primary function is to inactivate the C3 convertases by dissociating them into their constituent proteins (reviewed in ref.2). The importance of regulation is highlighted by the large number of human diseases that relate to inappropriate complement activation (3). Complement is also responsible for the primary rejection events in xenotransplantation; therefore, transgenic animals expressing human CD55 potentially provide a route to the generation of readily available organs that will resist rejection. Extended survival times have already been achieved for organs transplanted from human CD55-transgenic pigs to primates (4), and soluble CD55 has been demonstrated to block the Arthus reaction in vivo (5). Incorporation of CD55 into the envelope of baculovirus has proved to be a promising technology for prolonging the lifetime of virions used in genetic therapy (6). CD55 has additional roles, including acting as a binding partner for CD97 (7), a molecule whose expression is up-regulated on leukocytes during inflammatory activation. The significance of the CD97-CD55 interaction is little understood, but it has been implicated in the pathogenesis of multiple sclerosis, because CD97 and CD55, which are absent from normal white matter, are found at high levels in multiple sclerosis lesions (8). CD55 is expressed at a high level on all serum-exposed cells. Perhaps as a consequence of this expression, CD55 has been subverted by many bacterial and viral pathogens which exploit it as a receptor ...