In Vitro Evolution of Allergy Vaccine Candidates, with Maintained Structure, but Reduced B Cell and T Cell Activation Capacity

Allergy and asthma to cat (Felis domesticus) affects about 10% of the population in affluent countries. Immediate allergic symptoms are primarily mediated via IgE antibodies binding to B cell epitopes, whereas late phase inflammatory reactions are mediated via activated T cell recognition of allergen-specific T cell epitopes. Allergen-specific immunotherapy relieves symptoms and is the only treatment inducing a long-lasting protection by induction of protective immune responses. The aim of this study was to produce an allergy vaccine designed with the combined features of attenuated T cell activation, reduced anaphylactic properties, retained molecular integrity and induction of efficient IgE blocking IgG antibodies for safer and efficacious treatment of patients with allergy and asthma to cat. The template gene coding for rFel d 1 was used to introduce random mutations, which was subsequently expressed in large phage libraries. Despite accumulated mutations by up to 7 rounds of iterative error-prone PCR and biopanning, surface topology and structure was essentially maintained using IgE-antibodies from cat allergic patients for phage enrichment. Four candidates were isolated, displaying similar or lower IgE binding, reduced anaphylactic activity as measured by their capacity to induce basophil degranulation and, importantly, a significantly lower T cell reactivity in lymphoproliferative assays compared to the original rFel d 1. In addition, all mutants showed ability to induce blocking antibodies in immunized mice.The approach presented here provides a straightforward procedure to generate a novel type of allergy vaccines for safer and efficacious treatment of allergic patients

Family Business Restructuring:A Review and Research Agenda

Although business restructuring occurs frequently and it is important for the prosperity of family firms across generations, research on family firms has largely evolved separately from research on business restructuring. This is a missed opportunity, since the two domains are complementary, and understanding the context, process, content, and outcome dimensions is relevant to both research streams. We address this by examining the intersection between research on business restructuring and family firms to improve our knowledge of each area and inform future research. To achieve this goal, we review and organize research across different dimensions to create an integrative framework. Building on current research, we focus on 88 studies at the intersection of family firm and business restructuring research to develop a model that identifies research needs and suggests directions for future research

Comparison of heart rate measured by Polar RS 400 and ECG, validity and repeatability .

Aims: The purpose of this study was to investigate criterion-related validity and test–retest repeatability of the heart rate monitor Polar RS400 versus electrocardiogram (ECG). Methodology: Ten healthy subjects, 19–34 years, performed a cycle ergometer test 5 min on each load (50, 100 and 150 W). Heart rate (HR) was measured with ECG and Polar RS400 and recorded digitally. After at least one hour resting the test was repeated. Major findings: The results showed a significant correlation between HR measured by ECG and by Polar RS400 with correlation coefficients ranging from 0.97 to 1.00. In test 1 the mean difference ± 2SD between HR Polar and HR ECG was 0.7 ± 4.3 bpm and in test 2, 0.2 ± 3.2 bpm. In the repeated tests, the mean difference of HR between test 2 and test 1 ± 2SD was 3.2 ± 11.9 bpm with ECG and 2.6 ± 14.3 bpm with Polar RS400 and these differences were not statistically significant. Conclusion: This study indicates good criterion-related validity and test–retest repeatability of Polar RS400. Differences observed at individual levels should be noticed, but are not considered to be clinically important. Polar RS400 is thus well suited for recording HR during physical activity and exercise training

Suppression by neuropeptide Y of capsaicin-sensitive sensory nerve-mediated contraction in guinea-pig airways.

1. In the present study we have examined whether neuropeptide Y (NPY) interferes with non-adrenergic, non-cholinergic nerve-mediated contractions and relaxations in the guinea-pig airways. In these experiments we have used ring preparations of bronchi and trachea, incubated in the presence of atropine, propranolol and indomethacin (each 1 microM). 2. The contractile response to electrical stimulation of non-adrenergic, non-cholinergic nerve fibres was suppressed by NPY and NPY 13-36 in a concentration-dependent manner, these agents having similar inhibitory potencies. NPY caused a more complete inhibition than the C terminal fragment. 3. NPY affected neither the basal tension nor the substance P-evoked contraction in the bronchi and trachea and did not interfere with nerve-mediated, non-adrenergic relaxation in the trachea. 4. On the basis of these results, it is suggested that NPY may act on the terminals of sensory neurones in the airways to prevent antidromic, excitatory neurotransmission by inhibiting transmitter release