Immunomodulation in the treatment and/or prevention of bronchial asthma

ABSTRACTThe immunologic hallmark of atopic allergy and asthma is an increased production of IgE and T helper (h) type 2 cell cytokines (interleukin (IL)-4, IL-5, IL-9 and IL-13) by Th cells reacting to common environmental allergens. All of us inhale allergens and healthy non-atopics produce allergen-specific IgG1, IgG4 and the Th1 cytokine interferon-α, as well as IL-12 from macrophages. We now have many modalities of immunomodulation to decrease the effect of IL-4 or IL-5 or production and level of IgE or agents to shift the immune response from a Th2 to a Th1 response, thereby decreasing the allergic inflammatory response in the airways. In the present review we focus on conventional immunotherapy, mycobacterial vaccines, DNA vaccines using cytosine guanosine, inhibitors of IL-4 and IL-5 and anti-IgE: Omalizumab

Screen for Localized Proteins in Caulobacter crescentus

Precise localization of individual proteins is required for processes such as motility, chemotaxis, cell-cycle progression, and cell division in bacteria, but the number of proteins that are localized in bacterial species is not known. A screen based on transposon mutagenesis and fluorescence activated cell sorting was devised to identify large numbers of localized proteins, and employed in Caulobacter crescentus. From a sample of the clones isolated in the screen, eleven proteins with no previously characterized localization in C. crescentus were identified, including six hypothetical proteins. The localized hypothetical proteins included one protein that was localized in a helix-like structure, and two proteins for which the localization changed as a function of the cell cycle, suggesting that complex three-dimensional patterns and cell cycle-dependent localization are likely to be common in bacteria. Other mutants produced localized fusion proteins even though the transposon has inserted near the 5′ end of a gene, demonstrating that short peptides can contain sufficient information to localize bacterial proteins. The screen described here could be used in most bacterial species

A Generic System for the Expression and Purification of Soluble and Stable Influenza Neuraminidase

The influenza surface glycoprotein neuraminidase (NA) is essential for the efficient spread of the virus. Antiviral drugs such as Tamiflu (oseltamivir) and Relenza (zanamivir) that inhibit NA enzyme activity have been shown to be effective in the treatment of influenza infections. The recent ‘swine flu’ pandemic and world-wide emergence of Tamiflu-resistant seasonal human influenza A(H1N1) H274Y have highlighted the need for the ongoing development of new anti-virals, efficient production of vaccine proteins and novel diagnostic tools. Each of these goals could benefit from the production of large quantities of highly pure and stable NA. This publication describes a generic expression system for NAs in a baculovirus Expression Vector System (BEVS) that is capable of expressing milligram amounts of recombinant NA. To construct NAs with increased stability, the natural influenza NA stalk was replaced by two different artificial tetramerization domains that drive the formation of catalytically active NA homotetramers: GCN4-pLI from yeast or the Tetrabrachion tetramerization domain from Staphylothermus marinus. Both recombinant NAs are secreted as FLAG-tagged proteins to allow for rapid and simple purification. The Tetrabrachion-based NA showed good solubility, increased stability and biochemical properties closer to the original viral NA than the GCN4-pLI based construct. The expressed quantities and high quality of the purified recombinant NA suggest that this expression system is capable of producing recombinant NA for a broad range of applications including high-throughput drug screening, protein crystallisation, or vaccine development

Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a chronic antigen-driven allergic inflammatory disease, likely involving the interplay of genetic and environmental factors, yet their respective contributions to heritability are unknown

Do Adult Forms of Chronic Rhinosinusitis Exist in Children and Adolescents?

Pediatric chronic sinusitis is currently designated as pediatric chronic rhinosinusitis. In most pediatric cases, sinusitis is considered as infectious. In the adult literature, a wider repertoire of chronic rhinosinusitis conditions is recognized. In this review, the adult forms of chronic rhinosinusitis are used as a framework for identifying and defining the potential spectrum of pediatric chronic rhinosinusitis that exists beyond the most recognized condition, pediatric infectious chronic rhinosinusitis

Atopic Dermatitis is More than Skin Deep: A Commentary on Atopic Dermatitis and Review of Pertinent Publications from <i>Children</i> 2019–2021

The journal Children has a significant publication record on the topic of Atopic Dermatitis (AD) the past four years [...

Pediatric Chronic Rhinosinusitis: Unmet Needs

Pediatric chronic rhinosinusitis (CRS) remains an elusive diagnostic medical condition, largely based on imperfect diagnostic criteria, lack of controlled studies of therapy, lack of measure for resolution, and lack of information of pediatric sinus microbiome dysbiosis. The true prevalence of pediatric CRS is unknown, and symptoms often over-lap with other diagnoses. We review the unmet needs in pediatric CRS, to highlight potential research opportunities to improve understanding and therapy of the disease process