Neutrophil activation induces changes in the expression of surface receptors and may lead to degranulation. Surface expression of b2-integrins, L-selectin, complement receptor 1 (CR-1), decay-accelerating factor (DAF), C5a receptor, intercellular adhesion molecule-1 (ICAM-1) and ICAM-3 was compared by flow cytometry on isolated neutrophils stimulated with phorbol 12-myristate 13-acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine (FMLP), endotoxin or interleukin-8 and on neutrophils in whole blood anti-coagulated with the thrombin inhibitor lepirudin and stimulated with cobra venom factor to induce complement activation. Myeloperoxidase and lactoferrin in the supernatants were quantified in enzyme immunoassays. With high enough doses, all stimulants induced significant upregulation of b2-integrins, CR-1 and DAF and downregulation of L-selectin. ICAM-3 was either unchanged or somewhat downregulated. Only FMLP and PMA induced significant upregulation of ICAM-1. Combined measurement of b2-integrins and L-selectin permitted graded evaluation of early neutrophil activation. Measurement of degranulation showed no differences compared to unstimulated controls due to substantial spontaneous degranulation of isolated neutrophils by rewarming from 4 C and incubation at 37 C. Spontaneous activation was less in ethylenediaminetetraacetic acid-anti-coagulated blood, but calcium chelation may also inhibit the stimulated responses. There was large activation of unstimulated neutrophils in lepirudin-anti-coagulated blood at 37 C, obscuring changes induced by stimulation, which may render this anti-coagulant unsuitable for studies of neutrophils.
Interpersonal problems are significantly elevated in patients with depression. Metacognitive therapy (MCT) for depression does not address interpersonal problems but is associated with large reduction in depressive symptoms. The main aim of the current study was to explore whether MCT leads to improvements in interpersonal problems in patients with depression. The study was a waitlist controlled trial and assessments took place at pre- and post-treatment as well as 6-month follow-up. At pre-treatment, the sample had more interpersonal problems compared to samples from other studies of psychiatric outpatients. MCT was associated with large reductions in interpersonal problems. Level of interpersonal problems were not related to poorer treatment response. MCT, which does not directly target interpersonal problems, worked well for patients with depression and interpersonal problems. Future research should compare MCT with other evidence-based treatments for patients with depression and interpersonal problems.
Induction of CCR5 expression on Th2 clones was associated with secretion of some IFN-g. Moreover, the Th2-associated chemokine receptor CCR3 could be expressed on both Th1-dominant cell lines, and clones of Th1 and Th0 type after culture conditions with IL-4. This expression of CCR3 was associated with a reduced IFN-g production, but no IL-4 production could be induced. The IL-4-treated Th1 clones had a reduced migratory capacity against chemokines produced by ST cells compared to nonmanipulated T-cell clones. In contrast, the same IL-12-treated Th1 clones showed an increased migratory potential. Induction of the Th2-associated marker CCR3 on memory Th1 cells demonstrates that a change in chemokine receptor phenotype related to the Th2 type can be induced on terminally differentiated Th1 cells, without a change in the cytokine profile.
Introduction Generalized anxiety disorder (GAD) is characterized by persistent worry and anxiety, often with a chronic course. We tested the role of two suggested underlying factors in GAD, interpersonal problems and negative metacognitive beliefs, as predictors of trait‐worry and trait‐anxiety. Methods The sample consisted of 56 patients with a primary diagnosis of GAD from a randomized controlled trial. We first estimated the proportion of variance lying between the higher level of the data structure to account for potential therapists' effects. Two hierarchical regression analyses were conducted testing change in interpersonal problems and negative metacognitive beliefs as predictors of change in trait‐worry and trait‐anxiety following treatment. Change in depression and anxiety symptoms was controlled. Results Change in negative metacognitive beliefs was the strongest predictor of improvement of both trait‐worry and trait‐anxiety. Change in interpersonal problems was not a unique predictor of change in trait‐worry but did make a significant and unique contribution to trait‐anxiety. Conclusions Negative metacognitive beliefs may be important targets to improve trait‐worry and trait‐anxiety in GAD. Interpersonal problems may be relevant for trait‐anxiety but could also be a surface marker of higher order vulnerability factors. Implications for treatment are discussed.
Patients with Social Anxiety Disorder (SAD) typically report interpersonal problems, and these are important targets in treatment beyond social anxiety symptoms as they impair quality of life, maintain emotion symptoms and effect on social functioning. What factors contribute to interpersonal problems? In the current study we set out to explore the role of metacognitive beliefs as correlates of interpersonal problems in patients treated for SAD when controlling for the effect of social phobic cognitions and symptoms. The sample consisted of 52 patients with a primary diagnosis of SAD participating in a randomized controlled trial comparing cognitive therapy, paroxetine, pill placebo, or the combination of cognitive therapy and paroxetine in treating SAD. Two hierarchical multiple linear regression analyses were conducted to explore change in metacognitions as predictors of change in interpersonal problems when controlling for change in social phobic cognitions and social anxiety. Change in metacognitions accounted for unique variance in interpersonal problems improvement beyond change in cognitions. Furthermore, change in cognitions overlapped with change in social anxiety symptoms, and when controlling the overlap between these three predictors, only change in metacognitions was uniquely associated with improvement in interpersonal problems. This finding indicates that metacognitions are linked to interpersonal problems in patients with SAD with the implication that treatment should aim to modify metacognitive beliefs to alleviate interpersonal dysfunction.
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