Potent T cell response to a class I-binding 13-mer viral epitope and the influence of HLA micropolymorphism in controlling epitope length

The BZLF1 antigen of Epstein-Barr virus includes three overlapping sequences of different lengths that conform to the binding motif of human leukocyte antigen (HLA) B*3501. These 9-mer ((56)LPOGQLTAy(64)), 11-mer ((54)EPLPQGQLTAy(64)), and 13-mer ((52)LPEPLPQGQLTAY(64)) peptides all bound well to B*3501; however, the CTL response in individuals expressing this HILA allele was directed strongly and exclusively towards the 11-mer peptide. In contrast, EBV-exposed donors expressing HLA B*3503 showed no significant CTL response to these peptides because the single amino acid difference between B*3501 and B*3503 within the F pocket inhibited HLA binding by these peptides. The extraordinarily long 13-mer peptide was the target for the CTL response in individuals expressing B*3508, which differs from B*3501 at a single position within the D pocket (B*3501, 156 Leucine; B*3508, 156 Arginine). This minor difference was shown to enhance binding of the 13-mer peptide, presumably through a stabilizing interaction between the negatively charged glutamate at position 3 of the peptide and the positively charged arginine at HLA position 156. The 13-mer epitope defined in this study represents the longest class I-binding viral epitope identified to date as a minimal determinant. Furthermore, the potency of the response indicates that peptides of this length do not present a major structural barrier to CTL recognition.

The influence of antioxidant supplementation on markers of inflammation and the relationship to oxidative stress after exercise

Interest in the relationship between inflammation and oxidative stress has increased dramatically in recent years, not only within the clinical setting but also in the fields of exercise biochemistry and immunology. Inflammation and oxidative stress share a common role in the etiology of a variety Of Chronic diseases. During exercise, inflammation and oxidative stress are linked via muscle metabolism and muscle damage. Because oxidative stress and inflammation have traditionally been associated with fatigue and impaired recovery from exercise, research has focused on nutritional strategies aimed at reducing these effects. In this review, we have evaluated the findings of studies involving antioxidant supplementation on alterations in markers of inflammation (e.g., cytokines, C-reactive protein and cortisol). This review focuses predominantly on the role of reactive oxygen and nitrogen species generated from muscle metabolism and muscle damage during exercise and on the modulatory effects of antioxidant supplements. Furthermore, we have analyzed the influence of factors such as the dose, timing, supplementation period and bioavailability of antioxidant nutrients. (C) 2007 Elsevier Inc. All rights reserved.

Quality of life, stress and mental health in parents of children with parentally diagnosed food allergy compared to medically diagnosed and healthy controls

Background. Food allergy is related to poorer quality of life (QoL) and mental health of caregivers. Many parents diagnose food allergy in their child without seeking medical care and there is limited research on this group. This study investigated parental QoL and mental health in parents of children with parent-diagnosed food allergy (PA), medically diagnosed food allergy (MA), and a control group with no allergy (NA). Methods. One hundred and fifty parents from a general population completed validated measures of QoL, anxiety, depression, and stress. Results. Parents of children with food allergy (PA or MA) reported higher stress, anxiety, and depression than the control group (all ). Parents of children with MA reported poorer food allergy related QoL compared to parents of children with PA (); parents of children with PA reported poorer general QoL compared to parents of children with MA (). Conclusion. Parents of children with food allergy have significantly poorer mental health compared to healthy controls, irrespective of whether food allergy is medically diagnosed or not. It is important to encourage parents to have their child medically tested for food allergy and to recognise and refer for psychological support where needed.

Exploring quality of life in families of children living with and without a severe food allergy

This study aimed to explore the impact of food allergy on quality of life in children with food allergy and their primary caregivers, compared to a healthy non-food allergy comparison group. Food allergy children (n = 34) and control children (n = 15), aged 8–12, and their respective primary caregivers (n = 30/n = 13), completed generic quality of life scales (PedsQL™ and WHOQOLBREF) and were asked to take photographs and keep a diary about factors that they believed enhanced and/or limited their quality of life, over a one-week period. Questionnaire analysis showed that parents of children with food allergy had significantly lower quality of life in the social relationships domain and lower overall quality of life than the comparison parents. In contrast, children with food allergy had similar or higher quality of life scores compared to comparison children. Content analysis of photograph and diary data identified ten themes that influenced both child and parental quality of life. It was concluded that although food allergy influenced quality of life for some children, their parent's quality of life was hindered to a greater extent. The variability in findings highlights the importance of assessing quality of life in individual families, considering both children with allergies and their primary caregivers.

Early growth characteristics and the risk of reduced lung function and asthma : a meta-analysis of 25,000 children

Peer reviewed

Early growth characteristics and the risk of reduced lung function and asthma : a meta-analysis of 25,000 children

Peer reviewed

Childhood asthma exacerbations and the Arg16 β2-receptor polymorphism : a meta-analysis stratified by treatment

Peer reviewed

Development and validation of an attitudinal-profiling tool for patients with asthma

Peer reviewed

“Trying, But Failing” : The Role of Inhaler Technique and Mode of Delivery in Respiratory Medication Adherence

Peer reviewed

MACVIA clinical decision algorithm in adolescents and adults with allergic rhinitis

Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Mapping the Asthma Care Process : Implications for Research and Practice

The authors would like to thank the participants to the Respiratory Effectiveness Group Adherence symposium for their comments on the model overview presented during this meeting, members of the ASTRO-LAB consortium for collaborative work on reviewing literature and performing qualitative interviews, and patients and clinicians that shared valuable insights into asthma management during the telephone interviews.

Exchange protein directly activated by cyclic AMP (EPAC) activation reverses neutrophil dysfunction induced by β2-agonists, corticosteroids, and critical illness

Background Neutrophils play a role in the pathogenesis of asthma, chronic obstructive pulmonary disease, and pulmonary infection. Impaired neutrophil phagocytosis predicts hospital-acquired infection. Despite this, remarkably few neutrophil-specific treatments exist. 

Objectives We sought to identify novel pathways for the restoration of effective neutrophil phagocytosis and to activate such pathways effectively in neutrophils from patients with impaired neutrophil phagocytosis. 

Methods Blood neutrophils were isolated from healthy volunteers and patients with impaired neutrophil function. In healthy neutrophils phagocytic impairment was induced experimentally by using β₂-agonists. Inhibitors and activators of cyclic AMP (cAMP)-dependent pathways were used to assess the influence on neutrophil phagocytosis in vitro. 

Results β₂-Agonists and corticosteroids inhibited neutrophil phagocytosis. Impairment of neutrophil phagocytosis by β₂-agonists was associated with significantly reduced RhoA activity. Inhibition of protein kinase A (PKA) restored phagocytosis and RhoA activity, suggesting that cAMP signals through PKA to drive phagocytic impairment. However, cAMP can signal through effectors other than PKA, such as exchange protein directly activated by cyclic AMP (EPAC). An EPAC-activating analog of cAMP (8CPT-2Me-cAMP) reversed neutrophil dysfunction induced by β₂-agonists or corticosteroids but did not increase RhoA activity. 8CPT-2Me-cAMP reversed phagocytic impairment induced by Rho kinase inhibition but was ineffective in the presence of Rap-1 GTPase inhibitors. 8CPT-2Me-cAMP restored function to neutrophils from patients with known acquired impairment of neutrophil phagocytosis. 

Conclusions EPAC activation consistently reverses clinical and experimental impairment of neutrophil phagocytosis. EPAC signals through Rap-1 and bypasses RhoA. EPAC activation represents a novel potential means by which to reverse impaired neutrophil phagocytosis.