Pyrimidine 5'-nucleotidase deficiency: improved detection of carriers

The activities of pyrimidine 5'-nucleotidase (P5N) and the nucleotide pools in the erythrocytes from 19 members of a Dutch family with P5N deficiency were measured. In the erythrocytes of 5 (out of 6) apparent heterozygotes (based on P5N activities), an increased amount of UDP-N-acetylhexosamines was found. This increase was also found in the erythrocytes of 2 (out of 3) questionable heterozygotes (P5N activity below normal range, but not below normal mean--2 X SD) and not in the erythrocytes of family members with a normal P5N activity nor in erythrocytes from healthy donors. We conclude that analysis of the ribonucleotide patterns, in combination with determination of P5N activity, allows a more accurate diagnosis of heterozygosity for P5N.     

Examination of the stimulatory signaling potential of a channel catfish leukocyte immune-type receptor and associated adaptor

Expressed by various subsets of myeloid and lymphoid immune cells, channel catfish (Ictalurus punctatus) leukocyte immune-type receptors (IpLITRs) are predicted to play a key role in the initiation and termination of teleost cellular effector responses. These type I transmembrane proteins belong to the immunoglobulin superfamily and display features of immunoregulatory receptors with inhibitory and/or stimulatory signaling potential. Expanding on our previous work, which demonstrated that putative stimulatory IpLITR-types associated with the catfish adaptor proteins IpFcRγ and FcRγ-L, this study focuses on the functional significance of this immune receptor-adaptor signaling complex. Specifically, we generated an epitope-tagged chimeric receptor construct by fusing the extracellular domain of IpLITR 2.6b with the transmembrane region and cytoplasmic tail of IpFcRγ-L. This chimera was stably expressed in a rat basophilic leukemia (RBL) cell line, RBL-2H3, and following cross-linking of the surface receptor with an anti-hemagglutinin monoclonal antibody or opsonized microspheres, the chimeric teleost receptor induced cellular degranulation and phagocytic responses, respectively. Site-directed mutagenesis of the immunoreceptor tyrosine-based activation motif encoded within the cytoplasmic tail of the chimera confirmed that these functional responses were dependent on the phosphorylated tyrosines within this motif. Using a combination of phospho-specific antibodies and pharmacological inhibitors, we also demonstrate that the IpLITR/IpFcRγ-L-induced degranulation response requires the activity of Src homology 2 domain containing protein tyrosine phosphatases, phosphatidylinositol 3-kinase, protein kinase C, and mitogen-activated protein kinases but appears independent of the c-Jun N-terminal kinase and p38 MAP kinase pathways. In addition to this first look at stimulatory IpLITR-mediated signaling and its influence on cellular effector responses, the advantage of generating RBL-2H3 cells stably expressing a functional IpLITR-adaptor chimera will be discussed.     

Toll-like receptor 2 and 4 stimulation elicits an enhanced inflammatory response in human obese patients with atherosclerosis

The innate immune response elicited by activation of TLRs (Toll-like receptors) plays an important role in the pathogenesis of atherosclerosis. We hypothesized that cardiovascular risk factors are associated with the activation status of the innate immune system. We therefore assessed the responsiveness of TLRs on circulating cells in two groups of patients with established atherosclerosis and related this to the presence of cardiovascular risk factors. TNF (tumour necrosis factor)-α release induced by TLR2 and TLR4 activation was measured in patients with established coronary [PCI (percutaneous coronary intervention) study, n=78] or carotid artery disease [CEA (carotid endarterectomy) study, n=104], by stimulating whole blood samples with lipopolysaccharide (TLR4 ligand) and Pam3CSK4 [tripalmitoylcysteinylseryl-(lysyl)4; TLR2 ligand]. As an early activation marker, CD11b expression was measured by flow cytometry on CD14+ cells. Obesity was the 'only' risk factor that correlated with the TLR response. In both studies, obese patients had significantly higher TNF-α levels after stimulation of TLR2 compared with non-obese patients [16.9 (7.7-49.4) compared with 7.5 (1.5-19.2) pg/ml (P=0.008) in coronary artery disease and 14.6 (8.1-28.4) compared with 9.5 (6.1-15.7) pg/ml (P=0.015) in carotid artery disease; values are medians (interquartile range)]. Similar results were obtained following TLR4 stimulation. The enhanced inflammatory state in obese patients was also confirmed by a significant increased expression of the activation marker CD11b on circulating monocytes. In conclusion, obesity is associated with an enhanced TLR response in patients suffering from established atherosclerotic disease.     

Borderline traits and symptoms of post‐traumatic stress in a sample of female victims of intimate partner violence

Research has shown that symptoms of a post‐traumatic stress disorder (PTSD) are prevalent among victims of intimate partner violence (IPV). Furthermore, positive correlations have been reported between IPV victimization and borderline traits, and borderline traits and PTSD symptomatology. Although there is some evidence that individuals with a borderline disorder are vulnerable to developing PTSD after experiencing trauma, to our knowledge, this has never been studied empirically among a sample of victims of IPV in specific. However, the presence of borderline traits might place these victims at higher risk for developing PTSD symptoms as well. In the current study, associations between PTSD symptoms and borderline traits were examined in a Dutch sample of female help‐seeking victims of IPV (n = 120). As hypothesized, it was found that borderline traits significantly add to the vulnerability for development of PTSD in IPV victims, above and beyond the severity of IPV. Results are discussed in the light of practical implications like an early screening for borderline traits in treatment of victims of IPV. Copyright © 2010 John Wiley & Sons, Ltd.     

An analysis of matching cognitive-behavior therapy techniques to learning styles

Background and objectives

To optimize the effectiveness of cognitive-behavior therapy (CBT) for each individual patient, it is important to discern whether different intervention techniques may be differentially effective. One factor influencing the differential effectiveness of CBT intervention techniques may be the patient's preferred learning style, and whether this is ‘matched’ to the intervention.

Method

The current study uses a retrospective analysis to examine whether the impact of two common CBT interventions (thought records and behavioral experiments) is greater when the intervention is either matched or mismatched to the individual's learning style.

Results

Results from this study give some indication that greater belief change is achieved when the intervention technique is matched to participants' learning style, than when intervention techniques are mismatched to learning style.

Limitations

Conclusions are limited by the retrospective nature of the analysis and the limited dose of the intervention in non-clinical participants.

Conclusions

Results suggest that further investigation of the impact of matching the patient's learning style to CBT intervention techniques is warranted, using clinical samples with higher dose interventions.