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Pesquisa : D12.776.124.486.485.114 [Categoria DeCS]
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  1 / 84512 MEDLINE  
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PMID:29430664
Autor:Budzynska PM; Kyläniemi MK; Lassila O; Nera KP; Alinikula J
Endereço:Department of Medical Microbiology and Immunology, Institute of Biomedicine, University of Turku, Turku, Finland.
Título:BLIMP-1 is insufficient to induce antibody secretion in the absence of IRF4 in DT40 cells.
Fonte:Scand J Immunol; 87(3), 2018 Mar.
ISSN:1365-3083
País de publicação:England
Idioma:eng
Resumo:Differentiation of B cells into antibody-secreting cells (ASCs), plasmablasts and plasma cells is regulated by a network of transcription factors. Within this network, factors including PAX5 and BCL6 prevent ASC differentiation and maintain the B cell phenotype. In contrast, BLIMP-1 and high IRF4 expression promote plasma cell differentiation. BLIMP-1 is thought to induce immunoglobulin secretion, whereas IRF4 is needed for the survival of ASCs. The role of IRF4 in the regulation of antibody secretion has remained controversial. To study the role of IRF4 in the regulation of antibody secretion, we have created a double knockout (DKO) DT40 B cell line deficient in both IRF4 and BCL6. Although BCL6-deficient DT40 B cell line had upregulated BLIMP-1 expression and secreted antibodies, the DKO cell line did not. Even enforced BLIMP-1 expression in DKO cells or IRF4-deficient cells could not induce IgM secretion while in WT DT40 cells, it could. However, enforced IRF4 expression in DKO cells induced strong IgM secretion. Our findings support a model where IRF4 expression in addition to BLIMP-1 expression is required to induce robust antibody secretion.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Antibodies); 0 (Avian Proteins); 0 (IRF4 protein, Gallus gallus); 0 (Immunoglobulin M); 0 (Interferon Regulatory Factors); 0 (PAX5 Transcription Factor); 0 (Proto-Oncogene Proteins c-bcl-6); EC 2.1.1.- (Positive Regulatory Domain I-Binding Factor 1)


  2 / 84512 MEDLINE  
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PMID:29424453
Autor:Esenboga S; Cagdas D; Ozgur TT; Gur Cetinkaya P; Turkdemir LM; Sanal O; VanDerBurg M; Tezcan I
Endereço:Department of Pediatrics, Division of Immunology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Título:Clinical and genetic features of the patients with X-Linked agammaglobulinemia from Turkey: Single-centre experience.
Fonte:Scand J Immunol; 87(3), 2018 Mar.
ISSN:1365-3083
País de publicação:England
Idioma:eng
Resumo:X-linked agammaglobulinemia is a primary immunodeficiency disorder resulting from BTK gene mutations. There are many studies in the literature suggesting contradictory ideas about phenotype-genotype correlation. The aim of this study was to identify the mutations and clinical findings of patients with XLA in Turkey, to determine long-term complications related to the disease and to analyse the phenotype-genotype correlation. Thirty-two patients with XLA diagnosed between 1985 and 2016 in Pediatric Immunology Department of Hacettepe University Ihsan Dogramaci Children's Hospital were investigated. A clinical survey including clinical features of the patients was completed, and thirty-two patients from 26 different families were included in the study. Getting early diagnosis and regular assessment with imaging techniques seem to be the most important issues for improving the health status of the patients with XLA. Early molecular analysis gives chance for definitive diagnosis and genetic counselling, but not for predicting the clinical severity and prognosis.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Antibodies); 0 (Immunoglobulin A); 0 (Immunoglobulin G); 0 (Immunoglobulin M); EC 2.7.10.1 (Agammaglobulinaemia tyrosine kinase); EC 2.7.10.1 (Protein-Tyrosine Kinases)


  3 / 84512 MEDLINE  
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PMID:29314175
Autor:Cohn M
Endereço:Conceptual Immunology Group, The Salk Institute, La Jolla, CA, USA.
Título:Somatic diversification of the B cell repertoire requires two cell subsets.
Fonte:Scand J Immunol; 87(3), 2018 Mar.
ISSN:1365-3083
País de publicação:England
Idioma:eng
Resumo:Evolution found itself in a Catch-22 situation when selecting for the somatically derived paratopic repertoire of the humoral immune system. The B cell BCR repertoire can only be somatically diversified from a substrate of paratopes that is encoded in the germline. In order for the cells expressing that substrate to also be a target of germline selection, their BCRs must, independently, be of selective value by being expressed in a functionally important way in each individual. A somatically derived repertoire scrambles this substrate so that its specificities are lost, making it unselectable in the germline. Consequently, evolution faced an incompatibility. Here, we explore what it takes to resolve it.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Antibodies); 0 (Immunoglobulin Variable Region); 0 (Single-Domain Antibodies)


  4 / 84512 MEDLINE  
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PMID:28453681
Autor:Marks C; Nowak J; Klostermann S; Georges G; Dunbar J; Shi J; Kelm S; Deane CM
Endereço:Department of Statistics, University of Oxford, Oxford, UK.
Título:Sphinx: merging knowledge-based and ab initio approaches to improve protein loop prediction.
Fonte:Bioinformatics; 33(9):1346-1353, 2017 05 01.
ISSN:1367-4811
País de publicação:England
Idioma:eng
Resumo:Motivation: Loops are often vital for protein function, however, their irregular structures make them difficult to model accurately. Current loop modelling algorithms can mostly be divided into two categories: knowledge-based, where databases of fragments are searched to find suitable conformations and ab initio, where conformations are generated computationally. Existing knowledge-based methods only use fragments that are the same length as the target, even though loops of slightly different lengths may adopt similar conformations. Here, we present a novel method, Sphinx, which combines ab initio techniques with the potential extra structural information contained within loops of a different length to improve structure prediction. Results: We show that Sphinx is able to generate high-accuracy predictions and decoy sets enriched with near-native loop conformations, performing better than the ab initio algorithm on which it is based. In addition, it is able to provide predictions for every target, unlike some knowledge-based methods. Sphinx can be used successfully for the difficult problem of antibody H3 prediction, outperforming RosettaAntibody, one of the leading H3-specific ab initio methods, both in accuracy and speed. Availability and Implementation: Sphinx is available at http://opig.stats.ox.ac.uk/webapps/sphinx. Contact: deane@stats.ox.ac.uk. Supplementary information: Supplementary data are available at Bioinformatics online.
Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
Nome de substância:0 (Antibodies)


  5 / 84512 MEDLINE  
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PMID:28465009
Autor:Dong G; Kalifa R; Nath PR; Babichev Y; Gelkop S; Isakov N
Endereço:The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences and the Cancer Research Center, Ben Gurion University of the Negev, P.O.B. 653, Beer Sheva 84105, Israel. Electronic address: gdong@upenn.edu.
Título:Crk adaptor proteins regulate CD3ζ chain phosphorylation and TCR/CD3 down-modulation in activated T cells.
Fonte:Cell Signal; 36:117-126, 2017 Aug.
ISSN:1873-3913
País de publicação:England
Idioma:eng
Resumo:T cell receptor (TCR) recognition of a peptide antigen in the context of MHC molecules initiates positive and negative cascades that regulate T cell activation, proliferation and differentiation, and culminate in the acquisition of effector T cell functions. These processes are a prerequisite for the induction of specific T cell-mediated adaptive immune responses. A key event in the activation of TCR-coupled signaling pathways is the phosphorylation of tyrosine residues within the cytoplasmic tails of the CD3 subunits, predominantly CD3ζ. These transiently formed phosphotyrosyl epitopes serve as docking sites for SH2-domain containing effector molecules, predominantly the ZAP70 protein tyrosine kinase, which is critical for signal propagation. We found that CrkI and CrkII adaptor proteins also interact with CD3ζ in TCR activated-, but not in resting-, T cells. Crk binding to CD3ζ was independent of ZAP70 and also occurred in ZAP70-deficient T cells. Binding was mediated by Crk-SH2 domain interaction with phosphotyrosine-containing motifs on CD3ζ, via a direct physical interaction, as demonstrated by Far-Western blot. CrkII binding to CD3ζ could also be demonstrated in a heterologous system, where coexpression of a catalytically active Lck was used to phosphorylate the CD3ζ chain. TCR activation-induced Crk binding to CD3ζ resulted in increased and prolonged phosphorylation of CD3ζ, as well as ZAP70 and LAT, suggesting a positive role for CrkI/II binding to CD3ζ in regulation of TCR-coupled signaling pathways. Furthermore, Crk-dependent increased phosphorylation of CD3ζ coincided with inhibition of TCR downmodulation, supporting a positive role for Crk adaptor proteins in TCR-mediated signal amplification.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Antibodies); 0 (CD3 Complex); 0 (CRK protein, human); 0 (Cross-Linking Reagents); 0 (Proto-Oncogene Proteins c-crk); 0 (Receptors, Antigen, T-Cell); 0 (pervanadate); 21820-51-9 (Phosphotyrosine); 3WHH0066W5 (Vanadates); EC 2.7.10.2 (ZAP-70 Protein-Tyrosine Kinase); EC 2.7.10.2 (ZAP70 protein, human)


  6 / 84512 MEDLINE  
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PMID:29343722
Autor:Purohit S; Li T; Guan W; Song X; Song J; Tian Y; Li L; Sharma A; Dun B; Mysona D; Ghamande S; Rungruang B; Cummings RD; Wang PG; She JX
Endereço:Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA, 30912, USA.
Título:Multiplex glycan bead array for high throughput and high content analyses of glycan binding proteins.
Fonte:Nat Commun; 9(1):258, 2018 01 17.
ISSN:2041-1723
País de publicação:England
Idioma:eng
Resumo:Glycan-binding proteins (GBPs) play critical roles in diverse cellular functions such as cell adhesion, signal transduction and immune response. Studies of the interaction between GBPs and glycans have been hampered by the availability of high throughput and high-content technologies. Here we report multiplex glycan bead array (MGBA) that allows simultaneous analyses of 384 samples and up to 500 glycans in a single assay. The specificity, sensitivity and reproducibility of MGBA are evaluated using 39 plant lectins, 13 recombinant anti-glycan antibodies, and mammalian GBPs. We demonstrate the utility of this platform by the analyses of natural anti-glycan IgM and IgG antibodies in 961 human serum samples and the discovery of anti-glycan antibody biomarkers for ovarian cancer. Our data indicate that the MGBA platform is particularly suited for large population-based studies that require the analyses of large numbers of samples and glycans.
Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; VALIDATION STUDIES
Nome de substância:0 (Antibodies); 0 (Biomarkers, Tumor); 0 (Plant Lectins); 0 (Polysaccharides); 0 (Small Molecule Libraries)


  7 / 84512 MEDLINE  
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PMID:28470606
Autor:de Marco A
Endereço:Department of Biomedical Sciences and Engineering, University of Nova Gorica, Glavni Trg 9, SI-5261, Vipava, Slovenia. ario.demarco@ung.si.
Título:Acting on Folding Effectors to Improve Recombinant Protein Yields and Functional Quality.
Fonte:Methods Mol Biol; 1586:197-210, 2017.
ISSN:1940-6029
País de publicação:United States
Idioma:eng
Resumo:Molecular and chemical chaperones /foldases can strongly contribute to improve the amounts and the structural quality of recombinant proteins. Several methodologies have been proposed to optimize their beneficial effects. This chapter presents a condensed summary of the biotechnological opportunities offered by this approach followed by a protocol describing the method we use for expressing disulfide bond-dependent recombinant antibodies in the cytoplasm of bacteria engineered to overexpress sulfhydryl oxidase and DsbC isomerase. The system is based on the possibility to trigger the foldase expression independently and before the induction of the target protein. As a consequence, the recombinant antibody synthesis starts only after enough foldases have accumulated to promote correct folding of the antibody.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Antibodies); 0 (Escherichia coli Proteins); 0 (Protein Aggregates); 0 (Recombinant Proteins); EC 1.- (Oxidoreductases); EC 1.8.3.- (sulfhydryl oxidase); EC 5.3.4.1 (Protein Disulfide-Isomerases); EC 5.3.4.1 (dsbC protein, E coli)


  8 / 84512 MEDLINE  
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PMID:28448562
Autor:Moots RJ; Xavier RM; Mok CC; Rahman MU; Tsai WC; Al-Maini MH; Pavelka K; Mahgoub E; Kotak S; Korth-Bradley J; Pedersen R; Mele L; Shen Q; Vlahos B
Endereço:Aintree University Hospital, University of Liverpool, Liverpool, United Kingdom.
Título:The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study.
Fonte:PLoS One; 12(4):e0175207, 2017.
ISSN:1932-6203
País de publicação:United States
Idioma:eng
Resumo:OBJECTIVE: To assess the incidence of anti-drug antibodies (ADA) in patients with rheumatoid arthritis (RA) treated with the TNF inhibitors etanercept (ETN), adalimumab (ADL), or infliximab (IFX), and determine the potential relationship with trough drug concentration, efficacy, and patient-reported outcomes. METHODS: This multi-national, non-interventional, cross-sectional study (NCT01981473) enrolled adult patients with RA treated continuously for 6-24 months with ETN, ADL, or IFX. ADA and trough drug concentrations were measured by independent assays ≤2 days before the next scheduled dose. Efficacy measurements included Disease Activity Score 28-joint count (DAS28), low disease activity (LDA), remission, and erythrocyte sedimentation rate (ESR). Targeted medical histories of injection site/infusion reactions, serum sickness, and thromboembolic events were collected. RESULTS: Baseline demographics of the 595 patients (ETN: n = 200; ADL: n = 199; IFX: n = 196) were similar across groups. The mean duration of treatment was 14.6, 13.5, and 13.1 months for ETN, ADL, and IFX, respectively. All ETN-treated patients tested negative for ADA, whereas 31.2% and 17.4% patients treated with ADL and IFX, respectively, tested positive. In ADL- or IFX-treated patients, those with ADA had significantly lower trough drug concentrations. There were negative correlations between trough drug levels and both CRP and ESR in ADL- and IFX-treated patients. DAS28-ESR LDA and remission rates were higher in patients without ADA. The rate of targeted medical events reported was low. CONCLUSION: ADA were detected in ADL- and IFX-treated but not ETN-treated patients. Patients without ADA generally showed numerically better clinical outcomes than those with ADA. TRIAL REGISTRATION: This study was registered on www.ClinicalTrials.gov (NCT01981473).
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Antibodies); 0 (Antirheumatic Agents); B72HH48FLU (Infliximab); FYS6T7F842 (Adalimumab); OP401G7OJC (Etanercept)


  9 / 84512 MEDLINE  
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PMID:29197270
Autor:Majiya H; Adeyemi OO; Stonehouse NJ; Millner P
Endereço:School of Biomedical Sciences, University of Leeds, UK.
Título:Photodynamic inactivation of bacteriophage MS2: The A-protein is the target of virus inactivation.
Fonte:J Photochem Photobiol B; 178:404-411, 2018 Jan.
ISSN:1873-2682
País de publicação:Switzerland
Idioma:eng
Resumo:Singlet oxygen mediated oxidation has been shown to be responsible for photodynamic inactivation (PDI) of viruses in solution with photosensitisers such as 5, 10, 15, 20-tetrakis (1-methyl-4-pyridinio) porphyrin tetra p-toluenesulfonate (TMPyP). The capsids of non-enveloped viruses, such as bacteriophage MS2, are possible targets for viral inactivation by singlet oxygen oxidation. Within the capsid (predominantly composed of coat protein), the A-protein acts as the host recognition and attachment protein. The A-protein has two domains; an α-helix domain and a ß-sheet domain. The α-helix domain is attached to the viral RNA genome inside the capsid while the ß-sheet domain, which is on the surface of the capsid, is believed to be the site for attachment to the host bacteria pilus during infection. In this study, 4 sequence-specific antibodies were raised against 4 sites on the A-protein. Changes induced by the oxidation of singlet oxygen were compared to the rate of PDI of the virus. Using these antibodies, our results suggest that the rate of PDI is relative to loss of antigenicity of two sites on the A-protein. Our data further showed that PDI caused aggregation of MS2 particles and crosslinking of MS2 coat protein. However, these inter- and intra-capsid changes did not correlate to the rate of PDI we observed in MS2. Possible modes of action are discussed as a means to gaining insight to the targets and mechanisms of PDI of viruses.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Antibodies); 0 (Photosensitizing Agents); 0 (Porphyrins); 0 (Viral Proteins); 0 (maturation protein, Enterobacterio phage MS2); 17778-80-2 (Singlet Oxygen); 38673-65-3 (tetra(4-N-methylpyridyl)porphine)


  10 / 84512 MEDLINE  
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PMID:28454486
Autor:Eichinger CD; Hlady V
Endereço:Department of Bioengineering, University of Utah, 20 S. 2030 E., Rm. 108A, Salt Lake City, Utah 84112.
Título:Binary agonist surface patterns prime platelets for downstream adhesion in flowing whole blood.
Fonte:Biointerphases; 12(2):02C406, 2017 04 28.
ISSN:1559-4106
País de publicação:United States
Idioma:eng
Resumo:As platelets encounter damaged vessels or biomaterials, they interact with a complex milieu of surface-bound agonists, from exposed subendothelium to adsorbed plasma proteins. It has been shown that an upstream, surface-immobilized agonist is capable of priming platelets for enhanced adhesion downstream. In this study, binary agonists were integrated into the upstream position of flow cells and the platelet priming response was measured by downstream adhesion in flowing whole blood. A nonadditive response was observed in which platelets transiently exposed to two agonists exhibited greater activation and downstream adhesion than that from the sum of either agonist alone. Antibody blocking of one of the two upstream agonists eliminated nonadditive activation and downstream adhesion. Crosstalk between platelet activation pathways likely led to a synergistic effect which created an enhanced activation response in the platelet population. The existence of synergy between platelet priming pathways is a concept that has broad implications for the field of biomaterials hemocompatibility and platelet activity testing.
Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
Nome de substância:0 (Antibodies); 0 (Biocompatible Materials); 0 (Collagen Type I); 0 (von Willebrand Factor); 9001-32-5 (Fibrinogen)



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