8,106 research outputs found
Studies investigating peripheral blood derived cells that express the high affinity receptor for immunoglobulin E (Fc?RI) In Allergic Disorders
It is just forty years since the identification of immunoglobulin E (IgE) as the reagin responsible for allergen induced immediate hypersensitivity reactions. IgE exerts its biological actions through the binding of its Fc fragment to specific Fc receptors on effector cells. There are two predominant Fc receptors for IgE – Fc?RI, which has a very high affinity for IgE and Fc?RII, which shows less avid binding. For much of the first two decades after the identification of IgE, it was thought that Fc?RI expression was limited to mast cells and basophils and that IgE binding to other cell types such as Blymphocytes and antigen presenting cells (APCs) was mainly due to Fc?RII. However with major advances in characterisation and functional knowledge of Fc?RI, particularly in the last fifteen years, it has become apparent that Fc?RI can be expressed on several more cell types that may be involved in initiation and maintenance of allergic inflammation – including APCs (monocytes and dendritic cells)and possibly eosinophils.The research described in the four papers forming this thesis was completed during this period and evaluated Fc?RI expression on different cell types, their potential roles in allergen induced inflammatory responses and whether successful therapeutic strategies for allergic disorders may involve actions on Fc?RI+ cells. The relative expression of Fc?RI on peripheral blood basophils, monocytes and eosinophils from atopic and non-atopic subjects and any relationship with serum IgE concentrations was assessed in the first paper. The second study examined a potentially important role for basophils as a cellular source of rapidly releasable IL-4 which may help initiate allergen induced TH2 responses. The next study investigated the possible effects on allergen induced early and late asthmatic responses of the immunosuppressive drug cyclosporin A which had been shown both to inhibit mast cell and basophil degranulation and cytokine secretion (particularly by CD4+ T-cells). The final study evaluated Fc?RI expression on these cell types as well humoral factors (e.g. seasonal changes in allergen specific IgG and IgE) in subjects who, after 3 to 4 years of grass pollen immunotherapy, had continued on either active or placebo immunotherapy for a further 3 years. A historical perspective explaining some of the reasons the studies were done is provided in the introductory chapter whilst the discussion chapter at the end reviews how many of the findings of the study have evolved in subsequent years right up to the present day and finishes off with a brief synopsis of how rapidly increasing knowledge of the regulatory functions of dendritic cells (expressing Fc?RI and often monocyte derived) has resulted in better understanding of the mechanisms of allergen specific immunotherapy and is leading to more effective treatment modalities
Synthesis and Properties of New Dialkoxyphenylene Quinoxaline-Based Donor-Acceptor Conjugated Polymers and Their Applications on Thin Film Transistors and Solar Cells
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Adjuvant-free immunization with hemagglutinin-Fc fusion proteins as an approach to influenza vaccines
The hemagglutinins (HAs) of human H1 and H3 influenza viruses and avian H5 influenza virus were produced as recombinant fusion proteins with the human immunoglobulin Fc domain. Recombinant HA-human immunoglobulin Fc domain (HA-HuFc) proteins were secreted from baculovirus-infected insect cells as glycosylated oligomer HAs of the anticipated molecular mass, agglutinated red blood cells, were purified on protein A, and were used to immunize mice in the absence of adjuvant. Immunogenicity was demonstrated for all subtypes, with the serum samples demonstrating subtype-specific hemagglutination inhibition, epitope specificity similar to that seen with virus infection, and neutralization. HuFc-tagged HAs are potential candidates for gene-to-vaccine approaches to influenza vaccination
Studies investigating peripherial blood derived cells that express the high affinity receptor for immunoglobulin E (FceRI) in allergic disorders
It is just forty years since the identification of immunoglobulin E (IgE) as the reagin responsible for
allergen induced immediate hypersensitivity reactions. IgE exerts its biological actions through the
binding of its Fc fragment to specific Fc receptors on effector cells. There are two predominant Fc
receptors for IgE – Fc?RI, which has a very high affinity for IgE and Fc?RII, which shows less avid
binding. For much of the first two decades after the identification of IgE, it was thought that Fc?RI
expression was limited to mast cells and basophils and that IgE binding to other cell types such as Blymphocytes
and antigen presenting cells (APCs) was mainly due to Fc?RII . However with major
advances in characterisation and functional knowledge of Fc?RI, particularly in the last fifteen years, it
has become apparent that Fc?RI can be expressed on several more cell types that may be involved in
initiation and maintenance of allergic inflammation – including APCs (monocytes and dendritic cells)
and possibly eosinophils.The research described in the four papers forming this thesis was completed during this period and
evaluated Fc?RI expression on different cell types, their potential roles in allergen induced
inflammatory responses and whether successful therapeutic strategies for allergic disorders may
involve actions on Fc?RI+ cells. The relative expression of Fc?RI on peripheral blood basophils,
monocytes and eosinophils from atopic and non-atopic subjects and any relationship with serum IgE
concentrations was assessed in the first paper. The second study examined a potentially important role
for basophils as a cellular source of rapidly releasable IL-4 which may help initiate allergen induced
TH2 responses. The next study investigated the possible effects on allergen induced early and late
asthmatic responses of the immunosuppressive drug cyclosporin A which had been shown both to
inhibit mast cell and basophil degranulation and cytokine secretion (particularly by CD4+ T-cells). The
final study evaluated Fc?RI expression on these cell types as well humoral factors (e.g. seasonal
changes in allergen specific IgG and IgE) in subjects who, after 3 to 4 years of grass pollen
immunotherapy, had continued on either active or placebo immunotherapy for a further 3 years.A historical perspective explaining some of the reasons the studies were done is provided in the
introductory chapter whilst the discussion chapter at the end reviews how many of the findings of the
study have evolved in subsequent years right up to the present day and finishes off with a brief
synopsis of how rapidly increasing knowledge of the regulatory functions of dendritic cells (expressing
Fc?RI and often monocyte derived) has resulted in better understanding of the mechanisms of allergen
specific immunotherapy and is leading to more effective treatment modalities
Syntheses, structures, and properties of phenyltrihydrob orate complexes of zirconocene and titanocene
Lower serum viral loads in young patients with hepatitis B virus-related hepatocellular carcinoma.
The Reproducibility of Lists of Differentially Expressed Genes in Microarray Studies
Reproducibility is a fundamental requirement in scientific experiments and clinical contexts. Recent publications raise concerns about the reliability of microarray technology because of the apparent lack of agreement between lists of differentially expressed genes (DEGs). In this study we demonstrate that (1) such discordance may stem from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion, the lists become much more reproducible, especially when fewer genes are selected; and (3) the instability of short DEG lists based on P cutoffs is an expected mathematical consequence of the high variability of the t-values. We recommend the use of FC ranking plus a non-stringent P cutoff as a baseline practice in order to generate more reproducible DEG lists. The FC criterion enhances reproducibility while the P criterion balances sensitivity and specificity
Metabolism of territrem B and C in liver microsomes from 14-wk-old Wistar rats is catalyzed by cytochrome P-450 3A.
Pituitary adenylate cyclase-activating polypeptide acts synergistically with relaxin in modulating ovarian cell function in rats.
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