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  1 / 38122 MEDLINE  
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PMID:29337391
Autor:Ishii T; Niikura Y; Kurata K; Muroi M; Tanamoto K; Nagase T; Sakaguchi M; Yamashita N
Endereço:Department of Pharmacotherapy, Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan.
Título:Time-dependent distinct roles of Toll-like receptor 4 in a house dust mite-induced asthma mouse model.
Fonte:Scand J Immunol; 87(3), 2018 Mar.
ISSN:1365-3083
País de publicação:England
Idioma:eng
Resumo:House dust mites (HDMs) are a common source of allergens that trigger both allergen-specific and innate immune responses in humans. Here, we examined the effect of allergen concentration and the involvement of Toll-like receptor 4 (TLR4) in the process of sensitization to house dust mite allergens in an HDM extract-induced asthma mouse model. Intranasal administration of HDM extract induced an immunoglobulin E response and eosinophilic inflammation in a dose-dependent manner from 2.5 to 30 µg/dose. In TLR4-knockout mice, the infiltration of eosinophils and neutrophils into the lung was decreased compared with that in wild-type mice in the early phase of inflammation (total of three doses). However, in the late phase of inflammation (total of seven doses), eosinophil infiltration was significantly greater in TLR4-knockout mice than in wild-type mice. This suggests that the roles of TLR4 signaling are different between the early phase and the later phase of HDM allergen-induced inflammation. Thus, innate immune response through TLR4 regulated the response to HDM allergens, and the regulation was altered during the phase of inflammation.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Allergens); 0 (Antigens, Dermatophagoides); 0 (Tlr4 protein, mouse); 0 (Toll-Like Receptor 4); 37341-29-0 (Immunoglobulin E)


  2 / 38122 MEDLINE  
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PMID:29295972
Autor:Jabs F; Plum M; Laursen NS; Jensen RK; Mølgaard B; Miehe M; Mandolesi M; Rauber MM; Pfützner W; Jakob T; Möbs C; Andersen GR; Spillner E
Endereço:Immunological Engineering, Department of Engineering, Aarhus University, 8000, Aarhus, Denmark.
Título:Trapping IgE in a closed conformation by mimicking CD23 binding prevents and disrupts FcεRI interaction.
Fonte:Nat Commun; 9(1):7, 2018 01 02.
ISSN:2041-1723
País de publicação:England
Idioma:eng
Resumo:Anti-IgE therapeutics interfere with the ability of IgE to bind to its receptors on effector cells. Here we report the crystal structure of an anti-IgE single-domain antibody in complex with an IgE Fc fragment, revealing how the antibody inhibits interactions between IgE and the two receptors FcεRI and CD23. The epitope overlaps only slightly with the FcεRI-binding site but significantly with the CD23-binding site. Solution scattering studies of the IgE Fc reveal that antibody binding induces a half-bent conformation in between the well-known bent and extended IgE Fc conformations. The antibody acts as functional homolog of CD23 and induces a closed conformation of IgE Fc incompatible with FcεRI binding. Notably the antibody displaces IgE from both CD23 and FcεRI, and abrogates allergen-mediated basophil activation and facilitated allergen binding. The inhibitory mechanism might facilitate strategies for the future development of anti-IgE therapeutics for treatment of allergic diseases.
Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
Nome de substância:0 (Antibodies, Anti-Idiotypic); 0 (Epitopes); 0 (Immunoglobulin Fc Fragments); 0 (Receptors, IgE); 0 (Single-Domain Antibodies); 0 (anti-IgE antibodies); 37341-29-0 (Immunoglobulin E)


  3 / 38122 MEDLINE  
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PMID:29292940
Autor:Johansson E
Endereço:Karolinska Institutet - Enheten för dermatologi och venereologi, Institutionen för medicin Solna Stockholm, Sweden Karolinska Institutet - Enheten för dermatologi och venereologi, Institutionen för medicin Solna Stockholm, Sweden.
Título:Atopiskt eksem vanligt i alla åldrar - Nya rön om samsjuklighet till atopiskt eksem..
Fonte:Lakartidningen; 114, 2017 Nov 21.
ISSN:1652-7518
País de publicação:Sweden
Idioma:swe
Resumo:Atopic eczema common at all ages Eczema (atopic dermatitis) is an inflammatory skin disorder with dry skin and recurrent episodes of inflammation and itch. Onset is most common the first two years of life, but also occurs among older children, adolescents and adults. The prevalence of eczema has increased in Sweden and other industrialized countries the last decades; 15-30% of children and 2-10% of adults are affected. Approximately half of children with eczema early in life are in remission in adolescence. However, many of these will relapse later in life, often as hand eczema. Children with eczema are at increased risk to develop IgE sensitization to common food- and airborne allergens, food allergy, asthma and rhinitis. In addition, recent studies have reported that having eczema is associated with non-allergic disorders such as ADHD, depression and anxiety, epilepsy, overweight and obesity, cardiovascular disease, and different kinds of malignancies. There are also studies that have not found an association between eczema and the above mentioned non-allergic comorbidities. Thus, the association between eczema and non-allergic comorbidities are still largely unknown.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:37341-29-0 (Immunoglobulin E)


  4 / 38122 MEDLINE  
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PMID:28470742
Autor:Lee DD; Muskaj I; Savage W
Endereço:Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
Título:Platelet proteins cause basophil histamine release through an immunoglobulin-dependent mechanism.
Fonte:Transfusion; 57(7):1709-1716, 2017 07.
ISSN:1537-2995
País de publicação:United States
Idioma:eng
Resumo:BACKGROUND: A general understanding of allergic transfusion reaction mechanisms remains elusive. Multiple mechanisms have been proposed, but none have been compared experimentally. STUDY DESIGN AND METHODS: We used histamine release (HR) from healthy human donor basophils to model allergic transfusion reactions. Platelet component supernatant (plasma), platelet lysate, and manipulated platelet lysates (dialyzed, delipidated, trypsinized, mild heat-inactivated, and ultracentrifuged) were used to characterize allergic stimuli. Immunoglobulin-dependent mechanisms were investigated through cell surface immunoglobulin depletion and ibrutinib signaling inhibition. HR induced by platelet mitochondria was compared with HR by platelet lysate with or without DNase treatment. RESULTS: Robust, dose-responsive HR to platelet lysate was observed in two of eight nulliparous, never-transfused, healthy donors. No HR was observed with plasma. Among manipulated platelet lysates, only trypsin treatment significantly reduced HR (39% reduction; p = 0.008). HR in response to platelet lysate significantly decreased with either cell surface immunoglobulin depletion or ibrutinib pretreatment. Platelet mitochondria induced minimal basophil HR, and DNase treatment did not inhibit platelet lysate-induced HR. CONCLUSION: Type I immediate hypersensitivity to platelet proteins may be an allergic transfusion reaction mechanism. Prior sensitization to human proteins is not required for basophil responses to platelet proteins. Further study into the relative contributions of hypersensitivity to platelet versus plasma proteins in transfusion is warranted.
Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
Nome de substância:0 (Blood Proteins); 37341-29-0 (Immunoglobulin E)


  5 / 38122 MEDLINE  
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PMID:29386429
Autor:Uno K
Endereço:Faculty of Pharmacy, Chiba Institute of Science.
Título:[Pathogenic Mechanism and Diagnostic Testing for Drug Allergies].
Fonte:Yakugaku Zasshi; 138(2):151-167, 2018.
ISSN:1347-5231
País de publicação:Japan
Idioma:jpn
Resumo: Three stages of the pathogenic mechanism of drug allergies can be considered: antigen formation, immune reaction and inflammation/disorder reaction. Drugs are thought to form 4 types of antigens: drug only, polymers, drug-carrier conjugates, and metabolite-carrier complexes. Antigens are recognized by B cell receptors and T cell receptors. Helper T cells (Th) are differentiated into four subsets, namely, Th1, Th2, Th17 and regulatory T cells (Treg). Th1 produces interleukin (IL)-2 and interferon (IFN)-γ, and activates macrophages and cytotoxic T cells (Tc). Macrophages induce type IV allergies, and Tc lead to serious type IV allergies. On the other hand, Th2 produces IL-4, IL-5, and IL-6, etc., and activates B cells. B cells produce IgE antibodies, and the IgE antibody affects mast cells and induces type I allergies. Activated eosinophil leads to the chronic state of type I allergy. Diagnostic testing for allergenic drugs is necessary for patients with drug allergies. Because in vivo diagnostic tests for allergenic drugs are associated with a risk and burden to the patient, in vitro allergy tests are recommended to identify allergenic drugs. In allergy tests performed in vitro, cytological tests are more effective than serological tests, and the leukocyte migration test (LMT) presently has the highest efficacy. An LMT-chamber is better than LMT-agarose in terms of usability and sensitivity, and it can detect about 80% of allergenic drugs.
Tipo de publicação: JOURNAL ARTICLE; REVIEW
Nome de substância:0 (Antigens); 0 (Cytokines); 0 (Receptors, Antigen, B-Cell); 0 (Receptors, Antigen, T-Cell); 37341-29-0 (Immunoglobulin E)


  6 / 38122 MEDLINE  
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PMID:27779086
Autor:Cornejo-Garcia JA; Oussalah A; Blanca M; Gueant-Rodriguez RM; Mayorga C; Waton J; Barbaud A; Gaeta F; Romano A; Gueant JL
Título:Genetic Predictors of Drug Hypersensitivity.
Fonte:Curr Pharm Des; 22(45):6725-6733, 2016.
ISSN:1873-4286
País de publicação:Netherlands
Idioma:eng
Resumo:Our knowledge of genetic predisposing factors of drug hypersensitivity reactions (DHRs) is still scarce. The analysis of the genetic basis of these reactions may contribute to dissect the underlying mechanisms. We will outline current knowledge of the genetic predictors of most common DHRs, including reactions to betalactam antibiotics (BLs), nonsteroidal anti-inflammatory drugs (NSAIDs) and biological agents. The predictors of DHRs to BLs are mostly linked to IgE-class switching, IgE pathway and atopy (IL4R, NOD2, LGALS3) in replicated candidate gene studies, and to antigen presentation (HLA-DRA) in the single replicated GWAS performed so far. The HLA-DRA variants are predictors of allergy to penicillins, but not to cephalosporins and they influence also the sensitization against prevalent allergens. The predictors of DHRs against NSAIDs are mostly linked to metabolism of eicosanoids (ALOX5, ALOX5AP, TBXAS1, PTGDR, CYSLTR1). Single nucleotide polymorphisms (SNPs) in genes involved in histamine biosynthesis and antigen presentation, HLA, could also have a role in DHRs against NSAIDs. The intriguing association of DHRs to NSAIDs with atopy should deserve further attention. Predictors of DHRs against asparaginase and other biological agents relate to antigen presentation (HLA-DRB1 and HLA-A alleles, respectively). The potential relationship of genetic predictors of DHRs with pathomechanisms also involved in environmental exposure and atopy highlights the need to perform GWAS in contrasted populations, taking into account world-wide variations of allele frequencies and contrasted situations of environmental exposure.
Tipo de publicação: JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T
Nome de substância:0 (Anti-Bacterial Agents); 0 (Anti-Inflammatory Agents, Non-Steroidal); 37341-29-0 (Immunoglobulin E)


  7 / 38122 MEDLINE  
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PMID:29192831
Autor:Johnson JR; Harker JA
Endereço:1 School of Life and Health Sciences Aston University Birmingham, United Kingdom and.
Título:Allergic Airway Disease: More than Meets the IgE?
Fonte:Am J Respir Cell Mol Biol; 57(6):631-632, 2017 12.
ISSN:1535-4989
País de publicação:United States
Idioma:eng
Tipo de publicação: EDITORIAL
Nome de substância:0 (Allergens); 0 (FCER1A protein, human); 0 (Receptors, IgE); 37341-29-0 (Immunoglobulin E)


  8 / 38122 MEDLINE  
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PMID:29308841
Autor:Namazova-Barahona LS; Snovskaya MA; Mitushin IL; Kozhevnikova OV; Batyrova AS
Título:Peculiarities of Allergy Diagnosis in Children.
Fonte:Vestn Ross Akad Med Nauk; 72(1):33-41, 2017.
ISSN:0869-6047
País de publicação:Russia (Federation)
Idioma:eng
Resumo:Allergic disease is a serious problem in practical healthcare. Over the last 40 years there has been exponential growth in the prevalence. According to the world health organization information, allergic diseases are at the 2nd place in prevalence the children, behind the viral infections. Their frequency and severity are increasing. In this regard, the relevance of timely and skilled diagnostic allergopathology is most important. In this study the current state of the question of allergy diagnostics is considered, the international experience is summarized and the approach to the allergy diagnosis based on use of step-by-step identification of a causal and significant factor of allergic reactions is offered. On the basis of the analysis of relevance and the importance for patients of one or the other allergens (taking into account a source of allergens and age of patients) use of a step-by-step allergy diagnostics algorithm is offered. The first step is definition of clinical implications of an allergy. It means direct contact of the phisition with the patient, clarification of its complaints, clinical symptoms, medical history disease. The second step is the confirmation of IgE-dependent mechanism. It involves the using of screening tests that are selected depending on the clinical symptoms and seasonality manifestations (the screening module). The third step is to identify the source of the allergens that are most meaningful for the patient with using test panels (modules). The panels include the most common and clinically relevant triggers of allergic reactions. The fourth step is the search for an individual significant allergens, which were not included in the diagnostic modules. On the fifth step, we plan to conduct component-divided diagnostics and detect the antibodies to unique components of significant allergens. The developed diagnostics algorithm, corresponds to needs of both the adult, and children's population and provides the personalized approach to the patients.
Tipo de publicação: JOURNAL ARTICLE; REVIEW
Nome de substância:0 (Allergens); 37341-29-0 (Immunoglobulin E)


  9 / 38122 MEDLINE  
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PMID:29298008
Autor:Novik GA; Khaleva EG; Bychkova NV; Zdanova MV
Título:Evaluation of Efficacy and Safety of Longterm Feeding with Amino Acid-Based Formula in Infants with Cow's Milk Protein Allergy: Results of the Open-Label Prospective Controlled Post-Registration Trial.
Fonte:Vestn Ross Akad Med Nauk; 71(6):446-57, 2016.
ISSN:0869-6047
País de publicação:Russia (Federation)
Idioma:eng
Resumo:Background: The cow's milk allergy (CMA) prevalence is 2−3% in children under one year. Approximately in 5% of cases transferring to extensively hydrolysed formula (eHF) doesn't lead to disappearance of CMA symptoms. Aims: Evaluation of efficacy and safety of amino-acid formula (AAF) longterm feeding in children under one year and development of predictors of successful transfer from AAF to eHF. Materials and Methods: In open-label prospective post-registration trial duration of 365 days were included 43 children aged from 3 to 12 months with CMA. CMA was based on Russian and international guidelines. When a patient was included in the trial, child received eHF for 4 weeks with the evaluation of the effect of elimination diet (ED): in case of absence of effect, for diagnostic purposes child feed with AAF for 2 weeks and upon receiving the effect, child continued to receive it for at least 6 months. Diet was considered effective if there were observed disappearance of clinical manifestations of CMA during of formula using. Results: Children fed with AAF gain weight and increased height statistically higher during the first 6 months, compared with children receiving eHF, but without subsequent difference in a year. After 4 weeks' of AAF feeding, there was a significant decrease in SCORAD index from 46.84 (SD 4.164) to 2.52 (SD 2.204) (p=0.005); disappearance of gastrointestinal manifestations of CMA from 3 to 14 day. After 4 weeks, the 100% normalization of previously elevated faecal calprotectin (p<0.05) was observed; and after 6months. ED, in 60% of children normalization of the index of activation of basophils with milk was observed. 38.7% of children were transferred to eHF in 6 months, 12.9% and 25.8% in 9 and 12 months respectively. Conclusions: Use of AAF for children with CMA is an effective and safe treatment without lengthening the period of elimination, which is necessary for the formation of tolerance to cow's milk protein and has a positive impact on weight and height. Normalization of specific activation of basophils with milk could be considered as a predictor of successful transfer from AAF to eHF in children with CMA.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Amino Acids); 0 (Protein Hydrolysates); 37341-29-0 (Immunoglobulin E)


  10 / 38122 MEDLINE  
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PMID:27770477
Autor:Groh N; von Loetzen CS; Subbarayal B; Möbs C; Vogel L; Hoffmann A; Fötisch K; Koutsouridou A; Randow S; Völker E; Seutter von Loetzen A; Rösch P; Vieths S; Pfützner W; Bohle B; Schiller D
Endereço:Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.
Título:IgE and allergen-specific immunotherapy-induced IgG recognize similar epitopes of Bet v 1, the major allergen of birch pollen.
Fonte:Clin Exp Allergy; 47(5):693-703, 2017 May.
ISSN:1365-2222
País de publicação:England
Idioma:eng
Resumo:BACKGROUND: Allergen-specific immunotherapy (AIT) with birch pollen generates Bet v 1-specific immunoglobulin (Ig)G which blocks IgE-mediated hypersensitivity mechanisms. Whether IgG specific for Bet v 1a competes with IgE for identical epitopes or whether novel epitope specificities of IgG antibodies are developed is under debate. OBJECTIVE: We sought to analyze the epitope specificities of IgE and IgG antibodies from sera of patients who received AIT. METHODS: 15 sera of patients (13/15 received AIT) with Bet v 1a-specific IgE and IgG were analyzed. The structural arrangements of recombinant (r)Bet v 1a and rBet v 1a , modified in five potential epitopes, were analyzed by circular dichroism and nuclear magnetic resonance spectroscopy. IgE binding to Bet v 1 was assessed by ELISA and mediator release assays. Competitive binding of monoclonal antibodies specific for Bet v 1a and serum IgE/IgG to rBet v 1a and serum antibody binding to a non-allergenic Bet v 1-type model protein presenting an individual epitope for IgE was analyzed in ELISA and western blot. RESULTS: rBet v 1a had a Bet v 1a - similar secondary and tertiary structure. Monomeric dispersion of rBet v 1a was concentration and buffer-dependent. Up to 1500-fold increase in the EC for IgE-mediated mediator release induced by rBet v 1a was determined. The reduction of IgE and IgG binding to rBet v 1a was comparable in 67% (10/15) of sera. Bet v 1a-specific monoclonal antibodies inhibited binding of serum IgE and IgG to 66.1% and 64.9%, respectively. Serum IgE and IgG bound specifically to an individual epitope presented by our model protein in 33% (5/15) of sera. CONCLUSION AND CLINICAL RELEVANCE: Patients receiving AIT develop Bet v 1a-specific IgG which competes with IgE for partly identical or largely overlapping epitopes. The similarities of epitopes for IgE and IgG might stimulate the development of epitope-specific diagnostics and therapeutics.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Antigens, Plant); 0 (Epitopes); 0 (Immunoglobulin G); 126161-14-6 (Bet v 1 allergen, Betula); 37341-29-0 (Immunoglobulin E)



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