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[PMID]:28461446
[Au] Autor:Pequegnat B; Laird RM; Ewing CP; Hill CL; Omari E; Poly F; Monteiro MA; Guerry P
[Ad] Endereço:Department of Chemistry, University of Guelph, Guelph, Ontario, Canada.
[Ti] Título:Phase-Variable Changes in the Position of -Methyl Phosphoramidate Modifications on the Polysaccharide Capsule of Campylobacter jejuni Modulate Serum Resistance.
[So] Source:J Bacteriol;199(14), 2017 07 15.
[Is] ISSN:1098-5530
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:polysaccharide capsules (CPS) are characterized by the presence of nonstoichiometric -methyl phosphoramidate (MeOPN) modifications. The lack of stoichiometry is due to phase variation at homopolymeric tracts within the MeOPN transferase genes. strain 81-176 contains two MeOPN transferase genes and has been shown previously to contain MeOPN modifications at the 2 and 6 positions of the galactose (Gal) moiety in the CPS. We demonstrate here that one of the two MeOPN transferases, encoded by CJJ81176_1435, is bifunctional and is responsible for the addition of MeOPN to both the 2 and the 6 positions of Gal. A new MeOPN at the 4 position of Gal was observed in a mutant lacking the CJJ81176_1435 transferase and this was encoded by the CJJ81176_1420 transferase. During routine growth of 81-176, the CJJ81176_1420 transferase was predominantly in an off configuration, while the CJJ81176_1435 transferase was primarily on. However, exposure to normal human serum selected for cells expressing the CJJ81176_1420 transferase. MeOPN modifications appear to block binding of naturally occurring antibodies to the 81-176 CPS. The absence of MeOPN-4-Gal resulted in enhanced sensitivity to serum killing, whereas the loss of MeOPN-2-Gal and MeOPN-6-Gal resulted in enhanced resistance to serum killing, perhaps by allowing more MeOPN to be put onto the 4 position of Gal. undergoes phase variation in genes encoding surface antigens, leading to the concept that a strain of this organism consists of multiple genotypes that are selected for fitness in various environments. Methyl phosphoramidate modifications on the capsule of block access of preexisting antibodies in normal human sera to the polysaccharide chain, thus preventing activation of the classical arm of the complement cascade. We show that the capsule of strain 81-176 contains more sites of MeOPN modifications than previously recognized and that one site, on the 4 position of galactose, is more critical to complement resistance than the others. Exposure to normal human serum selects for variants in the population expressing this MeOPN modification.
[Mh] Termos MeSH primário: Amidas
Cápsulas Bacterianas/fisiologia
Campylobacter jejuni/metabolismo
Soros Imunes/imunologia
Ácidos Fosfóricos
Polissacarídeos Bacterianos/metabolismo
[Mh] Termos MeSH secundário: Animais
Anticorpos Antibacterianos
Clonagem Molecular
Regulação Bacteriana da Expressão Gênica/fisiologia
Epitopos Imunodominantes
Mutação
Polissacarídeos Bacterianos/química
Polissacarídeos Bacterianos/imunologia
Coelhos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amides); 0 (Antibodies, Bacterial); 0 (Immune Sera); 0 (Immunodominant Epitopes); 0 (Phosphoric Acids); 0 (Polysaccharides, Bacterial); 9Q189608GB (phosphoramidic acid)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:28467828
[Au] Autor:Ooi JD; Petersen J; Tan YH; Huynh M; Willett ZJ; Ramarathinam SH; Eggenhuizen PJ; Loh KL; Watson KA; Gan PY; Alikhan MA; Dudek NL; Handel A; Hudson BG; Fugger L; Power DA; Holt SG; Coates PT; Gregersen JW; Purcell AW; Holdsworth SR; La Gruta NL; Reid HH; Rossjohn J; Kitching AR
[Ad] Endereço:Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria 3168, Australia.
[Ti] Título:Dominant protection from HLA-linked autoimmunity by antigen-specific regulatory T cells.
[So] Source:Nature;545(7653):243-247, 2017 05 11.
[Is] ISSN:1476-4687
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Susceptibility and protection against human autoimmune diseases, including type I diabetes, multiple sclerosis, and Goodpasture disease, is associated with particular human leukocyte antigen (HLA) alleles. However, the mechanisms underpinning such HLA-mediated effects on self-tolerance remain unclear. Here we investigate the molecular mechanism of Goodpasture disease, an HLA-linked autoimmune renal disorder characterized by an immunodominant CD4 T-cell self-epitope derived from the α3 chain of type IV collagen (α3 ). While HLA-DR15 confers a markedly increased disease risk, the protective HLA-DR1 allele is dominantly protective in trans with HLA-DR15 (ref. 2). We show that autoreactive α3 -specific T cells expand in patients with Goodpasture disease and, in α3 -immunized HLA-DR15 transgenic mice, α3 -specific T cells infiltrate the kidney and mice develop Goodpasture disease. HLA-DR15 and HLA-DR1 exhibit distinct peptide repertoires and binding preferences and present the α3 epitope in different binding registers. HLA-DR15-α3 tetramer T cells in HLA-DR15 transgenic mice exhibit a conventional T-cell phenotype (T ) that secretes pro-inflammatory cytokines. In contrast, HLA-DR1-α3 tetramer T cells in HLA-DR1 and HLA-DR15/DR1 transgenic mice are predominantly CD4 Foxp3 regulatory T cells (T cells) expressing tolerogenic cytokines. HLA-DR1-induced T cells confer resistance to disease in HLA-DR15/DR1 transgenic mice. HLA-DR15 and HLA-DR1 healthy human donors display altered α3 -specific T-cell antigen receptor usage, HLA-DR15-α3 tetramer Foxp3 T and HLA-DR1-α3 tetramer Foxp3 CD25 CD127 T dominant phenotypes. Moreover, patients with Goodpasture disease display a clonally expanded α3 -specific CD4 T-cell repertoire. Accordingly, we provide a mechanistic basis for the dominantly protective effect of HLA in autoimmune disease, whereby HLA polymorphism shapes the relative abundance of self-epitope specific T cells that leads to protection or causation of autoimmunity.
[Mh] Termos MeSH primário: Doença Antimembrana Basal Glomerular/imunologia
Autoimunidade/imunologia
Linfócitos T Reguladores/imunologia
[Mh] Termos MeSH secundário: Animais
Doença Antimembrana Basal Glomerular/patologia
Sequência de Bases
Linfócitos T CD4-Positivos/imunologia
Colágeno Tipo IV/química
Colágeno Tipo IV/imunologia
Citocinas/imunologia
Feminino
Fatores de Transcrição Forkhead/metabolismo
Subtipos Sorológicos de HLA-DR/imunologia
Antígeno HLA-DR1/imunologia
Seres Humanos
Epitopos Imunodominantes
Masculino
Camundongos
Camundongos Transgênicos
Modelos Moleculares
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Collagen Type IV); 0 (Cytokines); 0 (Forkhead Transcription Factors); 0 (Foxp3 protein, mouse); 0 (HLA-DR Serological Subtypes); 0 (HLA-DR1 Antigen); 0 (HLA-DR15 antigen); 0 (Immunodominant Epitopes)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1038/nature22329


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[PMID]:29206240
[Au] Autor:Treat BR; Bidula SM; Ramachandran S; St Leger AJ; Hendricks RL; Kinchington PR
[Ad] Endereço:Molecular Virology and Microbiology Graduate Program, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
[Ti] Título:Influence of an immunodominant herpes simplex virus type 1 CD8+ T cell epitope on the target hierarchy and function of subdominant CD8+ T cells.
[So] Source:PLoS Pathog;13(12):e1006732, 2017 Dec.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Herpes simplex virus type 1 (HSV-1) latency in sensory ganglia such as trigeminal ganglia (TG) is associated with a persistent immune infiltrate that includes effector memory CD8+ T cells that can influence HSV-1 reactivation. In C57BL/6 mice, HSV-1 induces a highly skewed CD8+ T cell repertoire, in which half of CD8+ T cells (gB-CD8s) recognize a single epitope on glycoprotein B (gB498-505), while the remainder (non-gB-CD8s) recognize, in varying proportions, 19 subdominant epitopes on 12 viral proteins. The gB-CD8s remain functional in TG throughout latency, while non-gB-CD8s exhibit varying degrees of functional compromise. To understand how dominance hierarchies relate to CD8+ T cell function during latency, we characterized the TG-associated CD8+ T cells following corneal infection with a recombinant HSV-1 lacking the immunodominant gB498-505 epitope (S1L). S1L induced a numerically equivalent CD8+ T cell infiltrate in the TG that was HSV-specific, but lacked specificity for gB498-505. Instead, there was a general increase of non-gB-CD8s with specific subdominant epitopes arising to codominance. In a latent S1L infection, non-gB-CD8s in the TG showed a hierarchy targeting different epitopes at latency compared to at acute times, and these cells retained an increased functionality at latency. In a latent S1L infection, these non-gB-CD8s also display an equivalent ability to block HSV reactivation in ex vivo ganglionic cultures compared to TG infected with wild type HSV-1. These data indicate that loss of the immunodominant gB498-505 epitope alters the dominance hierarchy and reduces functional compromise of CD8+ T cells specific for subdominant HSV-1 epitopes during viral latency.
[Mh] Termos MeSH primário: Linfócitos T CD8-Positivos/virologia
Herpes Simples/imunologia
Herpesvirus Humano 1/imunologia
Epitopos Imunodominantes/metabolismo
Gânglio Trigeminal/virologia
Proteínas do Envelope Viral/metabolismo
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
Linfócitos T CD8-Positivos/imunologia
Linfócitos T CD8-Positivos/patologia
Linhagem Celular
Células Cultivadas
Cercopithecus aethiops
DNA Recombinante/metabolismo
Infecções Oculares Virais/imunologia
Infecções Oculares Virais/metabolismo
Infecções Oculares Virais/patologia
Infecções Oculares Virais/virologia
Feminino
Deleção de Genes
Herpes Simples/metabolismo
Herpes Simples/patologia
Herpes Simples/virologia
Herpesvirus Humano 1/fisiologia
Camundongos Endogâmicos C57BL
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/metabolismo
Mutação Puntual
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Gânglio Trigeminal/imunologia
Gânglio Trigeminal/patologia
Células Vero
Proteínas do Envelope Viral/química
Proteínas do Envelope Viral/genética
Ativação Viral
Latência Viral
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Recombinant); 0 (Immunodominant Epitopes); 0 (Peptide Fragments); 0 (Recombinant Fusion Proteins); 0 (Viral Envelope Proteins); 0 (glycoprotein B, human herpesvirus 1)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180210
[Lr] Data última revisão:
180210
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006732


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[PMID]:29232408
[Au] Autor:Malik A; Adland E; Laker L; Kløverpris H; Fardoos R; Roider J; Severinsen MC; Chen F; Riddell L; Edwards A; Buus S; Jooste P; Matthews PC; Goulder PJR
[Ad] Endereço:Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
[Ti] Título:Immunodominant cytomegalovirus-specific CD8+ T-cell responses in sub-Saharan African populations.
[So] Source:PLoS One;12(12):e0189612, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:More than 90% of children in Africa are infected with cytomegalovirus (CMV) by the age of 12 months. However, the high-frequency, immunodominant CD8+ T-cell responses that control CMV infection have not been well studied in African populations. We therefore sought to define the immunodominant CMV-specific CD8+ T-cell responses within sub-Saharan African study subjects. Among 257 subjects, we determined the CD8+ T-cell responses to overlapping peptides spanning three of the most immunogenic CMV proteins, pp65, IE-1 and IE-2, using IFN-γ ELISpot assays. A bioinformatics tool was used to predict optimal epitopes within overlapping peptides whose recognition was statistically associated with expression of particular HLA class I molecules. Using this approach, we identified 16 predicted novel CMV-specific epitopes within CMV-pp65, IE-1 and IE-2. The immunodominant pp65-specific, IE-1, IE-2 responses were all either previously well characterised or were confirmed using peptide-MHC tetramers. The novel epitopes identified included an IE-2-specific epitope restricted by HLA*B*44:03 that induced high-frequency CD8+ T-cell responses (mean 3.4% of CD8+ T-cells) in 95% of HLA-B*44:03-positive subjects tested, in one individual accounting for 18.8% of all CD8+ T-cells. These predicted novel CMV-specific CD8+ T-cell epitopes identified in an African cohort will facilitate future analyses of immune responses in African populations where CMV infection is almost universal during infancy.
[Mh] Termos MeSH primário: Linfócitos T CD8-Positivos/imunologia
Citomegalovirus/imunologia
Epitopos Imunodominantes/imunologia
[Mh] Termos MeSH secundário: Adulto
África ao Sul do Saara
Estudos de Coortes
Ensaio de Imunoadsorção Enzimática
Feminino
Seres Humanos
Masculino
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Immunodominant Epitopes)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189612


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[PMID]:28938005
[Au] Autor:Holanda RA; Muñoz JE; Dias LS; Silva LBR; Santos JRA; Pagliari S; Vieira ÉLM; Paixão TA; Taborda CP; Santos DA; Bruña-Romero O
[Ad] Endereço:Departamento de Microbiologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
[Ti] Título:Recombinant vaccines of a CD4+ T-cell epitope promote efficient control of Paracoccidioides brasiliensis burden by restraining primary organ infection.
[So] Source:PLoS Negl Trop Dis;11(9):e0005927, 2017 Sep.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Paracoccidioidomycosis (PCM) is an infectious disease endemic to South America, caused by the thermally dimorphic fungi Paracoccidioides. Currently, there is no effective human vaccine that can be used in prophylactic or therapeutic regimes. We tested the hypothesis that the immunogenicity of the immunodominant CD4+ T-cell epitope (P10) of Paracoccidioides brasiliensis gp43 antigen might be significantly enhanced by using a hepatitis B virus-derived particle (VLP) as an antigen carrier. This chimera was administered to mice as a (His)6-purified protein (rPbT) or a replication-deficient human type 5 adenoviral vector (rAdPbT) in an immunoprophylaxis assay. The highly virulent Pb18 yeast strain was used to challenge our vaccine candidates. Fungal challenge evoked robust P10-specific memory CD4+ T cells secreting protective Th-1 cytokines in most groups of immunized mice. Furthermore, the highest level of fungal burden control was achieved when rAdPbT was inoculated in a homologous prime-boost regimen, with 10-fold less CFU recovering than in non-vaccinated mice. Systemic Pb18 spreading was only prevented when rAdPbT was previously inoculated. In summary, we present here VLP/P10 formulations as vaccine candidates against PCM, some of which have demonstrated for the first time their ability to prevent progression of this pernicious fungal disease, which represents a significant social burden in developing countries.
[Mh] Termos MeSH primário: Antígenos de Fungos/imunologia
Linfócitos T CD4-Positivos/imunologia
Epitopos de Linfócito T/imunologia
Proteínas Fúngicas/imunologia
Vacinas Fúngicas/administração & dosagem
Glicoproteínas/imunologia
Paracoccidioides/crescimento & desenvolvimento
Paracoccidioides/imunologia
Paracoccidioidomicose/prevenção & controle
[Mh] Termos MeSH secundário: Animais
Citocinas/imunologia
Citocinas/secreção
Epitopos de Linfócito T/genética
Vacinas Fúngicas/imunologia
Vírus da Hepatite B/genética
Imunização
Epitopos Imunodominantes/imunologia
Imunogenicidade da Vacina
Memória Imunológica
Fígado/microbiologia
Pulmão/microbiologia
Camundongos Endogâmicos BALB C
Paracoccidioidomicose/imunologia
Paracoccidioidomicose/microbiologia
Baço/microbiologia
Células Th1/imunologia
Vacinas Sintéticas/administração & dosagem
Vacinas Sintéticas/genética
Vacinas Sintéticas/imunologia
Vacinas de Partículas Semelhantes a Vírus/administração & dosagem
Vacinas de Partículas Semelhantes a Vírus/genética
Vacinas de Partículas Semelhantes a Vírus/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (43 kDa protein, Paracoccidioides); 0 (Antigens, Fungal); 0 (Cytokines); 0 (Epitopes, T-Lymphocyte); 0 (Fungal Proteins); 0 (Fungal Vaccines); 0 (Glycoproteins); 0 (Immunodominant Epitopes); 0 (Vaccines, Synthetic); 0 (Vaccines, Virus-Like Particle)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170923
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005927


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[PMID]:28934427
[Au] Autor:Tzannou I; Nicholas SK; Lulla P; Aguayo-Hiraldo PI; Misra A; Martinez CA; Machado AA; Orange JS; Piedra PA; Vera JF; Leen AM
[Ad] Endereço:Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, and Houston Methodist Hospital.
[Ti] Título:Immunologic Profiling of Human Metapneumovirus for the Development of Targeted Immunotherapy.
[So] Source:J Infect Dis;216(6):678-687, 2017 Sep 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human metapneumovirus (hMPV) is a respiratory virus detected in ≥9% of allogeneic hematopoietic stem cell transplant (HSCT) recipients, in whom it can cause significant morbidity and mortality. Given the lack of effective antivirals, we investigated the potential for immunotherapeutic intervention, using adoptively transferred T cells. Thus, we characterized the cellular immune response to the virus and identified F, N, M2-1, M, and P as immunodominant target antigens. Reactive T cells were polyclonal (ie, they expressed CD4 and CD8), T-helper type 1 polarized, and polyfunctional (ie, they produced interferon γ, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, and granzyme B), and they were able to kill autologous antigen-loaded targets. The detection of hMPV-specific T cells in HSCT recipients who endogenously controlled active infections support the clinical importance of T-cell immunity in mediating protective antiviral effects. Our results demonstrate the feasibility of developing an immunotherapy for immunocompromised patients with uncontrolled infections.
[Mh] Termos MeSH primário: Imunoterapia Adotiva
Metapneumovirus/imunologia
Infecções por Paramyxoviridae/terapia
[Mh] Termos MeSH secundário: Adulto
Estudos de Viabilidade
Feminino
Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia
Granzimas/imunologia
Seres Humanos
Imunidade Celular
Hospedeiro Imunocomprometido/imunologia
Epitopos Imunodominantes/imunologia
Interferon gama/imunologia
Leucócitos Mononucleares/virologia
Masculino
Metapneumovirus/isolamento & purificação
Meia-Idade
Infecções por Paramyxoviridae/imunologia
Linfócitos T/virologia
Fator de Necrose Tumoral alfa/imunologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Immunodominant Epitopes); 0 (Tumor Necrosis Factor-alpha); 82115-62-6 (Interferon-gamma); 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor); EC 3.4.21.- (Granzymes)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix358


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[PMID]:28855032
[Au] Autor:Wang X; Zhang Y; Hu M; Wang R; Liu L; Qian K; Li Y; Zhi X
[Ad] Endereço:Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
[Ti] Título:[Prognostic and Predictive Value of Thyroid Transcription Factor-1, CD56, P40 and Other Clinical Characteristics in Small Cell Lung Cancer Patients].
[So] Source:Zhongguo Fei Ai Za Zhi;20(8):522-527, 2017 Aug 20.
[Is] ISSN:1999-6187
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:BACKGROUND: The aim of this study is to explore roles of thyroid transcription factor-1 (TTF-1), CD56, P40 expression and other clinical characteristics predicting response and survival in patients with small cell lung cancer (SCLC). METHODS: Formalin-fixed, paraffin-embedded biopsy tissues were retrospectively obtained from 198 SCLC patients who were diagnosed first in Xuanwu Hospital. The expressions of TTF-1, CD56 and P40 were detected by immunohistochemistry. The clinical data including age, gender, cancer stage, Eastern Cooperative Oncology Group (ECOG) score, smoking or not, superior vena cava syndrome (SVCS) due to lung cancer or not were collected. Cox proportional hazard model was used to analyze the relationship between the overall survival (OS) and factors. RESULTS: Immunohistochemical staining results showed the positive rate of TTF-1, CD56, P40 were 73.2%, 88.4% and 7.1% respectively. TTF-1 expression (OR=0.665, 95%CI: 0.472-0.937), smoking index ≤400 (OR=1.72, 95%CI: 1.061-2.789) and ECOG=2 (OR=3.551, 95%CI: 2.133-5.914), extensive-stage (OR=2.487, 95%CI: 1.793-3.451) and SVCS due to lung cancer (OR=2.394, 95%CI: 1.49-3.846) were independent prognostic factors for SCLC patients. CONCLUSIONS: Prognosis of SCLC was related to TTF-1 expression independently after adjusting smoking, ECOG score, stage and SVCS due to lung cancer. Detection of TTF-1, CD56 and P40 expression level might be helpful for predict the prognosis of SCLC.
.
[Mh] Termos MeSH primário: Antígeno CD56/metabolismo
Epitopos Imunodominantes/metabolismo
Neoplasias Pulmonares/metabolismo
Proteínas Nucleares/metabolismo
Fragmentos de Peptídeos/metabolismo
Carcinoma de Pequenas Células do Pulmão/metabolismo
Fatores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Biomarcadores Tumorais/genética
Biomarcadores Tumorais/metabolismo
Antígeno CD56/genética
Feminino
Seres Humanos
Epitopos Imunodominantes/genética
Neoplasias Pulmonares/genética
Neoplasias Pulmonares/mortalidade
Neoplasias Pulmonares/patologia
Masculino
Meia-Idade
Estadiamento de Neoplasias
Proteínas Nucleares/genética
Fragmentos de Peptídeos/genética
Prognóstico
Estudos Retrospectivos
Carcinoma de Pequenas Células do Pulmão/genética
Carcinoma de Pequenas Células do Pulmão/mortalidade
Carcinoma de Pequenas Células do Pulmão/patologia
Fator Nuclear 1 de Tireoide
Fatores de Transcrição/genética
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (CD56 Antigen); 0 (Immunodominant Epitopes); 0 (NCAM1 protein, human); 0 (NKX2-1 protein, human); 0 (Nuclear Proteins); 0 (P40, iodinated C-terminal peptide, human); 0 (Peptide Fragments); 0 (Thyroid Nuclear Factor 1); 0 (Transcription Factors)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.3779/j.issn.1009-3419.2017.08.04


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[PMID]:28787455
[Au] Autor:Gorin AM; Du Y; Liu FY; Zhang TH; Ng HL; Hofmann C; Cumberland WG; Sun R; Yang OO
[Ad] Endereço:Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
[Ti] Título:HIV-1 epitopes presented by MHC class I types associated with superior immune containment of viremia have highly constrained fitness landscapes.
[So] Source:PLoS Pathog;13(8):e1006541, 2017 Aug.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Certain Major Histocompatibility-I (MHC-I) types are associated with superior immune containment of HIV-1 infection by CD8+ cytotoxic T lymphocytes (CTLs), but the mechanisms mediating this containment are difficult to elucidate in vivo. Here we provide controlled assessments of fitness landscapes and CTL-imposed constraints for immunodominant epitopes presented by two protective (B*57 and B*27) and one non-protective (A*02) MHC-I types. Libraries of HIV-1 with saturation mutagenesis of CTL epitopes are propagated with and without CTL selective pressure to define the fitness landscapes for epitope mutation and escape from CTLs via deep sequencing. Immunodominant B*57- and B*27- present epitopes are highly limited in options for fit mutations, with most viable variants recognizable by CTLs, whereas an immunodominant A*02 epitope-presented is highly permissive for mutation, with many options for CTL evasion without loss of viability. Generally, options for evasion overlap considerably between CTL clones despite highly distinct T cell receptors. Finally, patterns of variant recognition suggest population-wide CTL selection for the A*02-presented epitope. Overall, these findings indicate that these protective MHC-I types yield CTL targeting of highly constrained epitopes, and underscore the importance of blocking public escape pathways for CTL-based interventions against HIV-1.
[Mh] Termos MeSH primário: Apresentação do Antígeno/imunologia
Epitopos de Linfócito T/imunologia
Infecções por HIV/imunologia
Antígenos de Histocompatibilidade Classe I/imunologia
Linfócitos T Citotóxicos/imunologia
[Mh] Termos MeSH secundário: HIV-1/imunologia
Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Evasão da Resposta Imune/imunologia
Epitopos Imunodominantes/imunologia
Mutagênese Sítio-Dirigida
Viremia/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Epitopes, T-Lymphocyte); 0 (Histocompatibility Antigens Class I); 0 (Immunodominant Epitopes)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170809
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006541


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[PMID]:28768877
[Au] Autor:Schöne D; Hrycak CP; Windmann S; Lapuente D; Dittmer U; Tenbusch M; Bayer W
[Ad] Endereço:Institute for Virology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
[Ti] Título:Immunodominance of Adenovirus-Derived CD8 T Cell Epitopes Interferes with the Induction of Transgene-Specific Immunity in Adenovirus-Based Immunization.
[So] Source:J Virol;91(20), 2017 Oct 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Adenovirus (Ad)-based immunization is a popular approach in vaccine development, and Ad-based vectors are renowned for their potential to induce strong CD8 T cell responses to the encoded transgene. Surprisingly, we previously found in the mouse Friend retrovirus (FV) model that Ad-based immunization did not induce CD8 T cell responses to the FV Leader-Gag-derived immunodominant epitope GagL We show now that induction of GagL -specific CD8 T cells was highly effective when leader-Gag was delivered by plasmid DNA immunization, implying a role for Ad-derived epitopes in mediating unresponsiveness. By immunizing with DNA constructs encoding strings of GagL and the two Ad-derived epitopes DNA-binding protein (DBP ) and hexon , we confirmed that Ad epitopes prevent induction of GagL -specific CD8 T cells. Interestingly, while DBP did not interfere with GagL -specific CD8 T cell induction, the H-2D -restricted hexon suppressed the CD8 T cell response to the H-2D -restricted GagL strongly in H-2 mice but not in H-2 mice. This finding indicates that competition occurs at the level of responding CD8 T cells, and we could indeed demonstrate that coimmunization with an interleukin 2 (IL-2)-encoding plasmid restored GagL -specific CD8 T cell responses to epitope strings in the presence of hexon IL-2 codelivery did not restore GagL responsiveness in Ad-based immunization, however, likely due to the presence of further epitopes in the Ad vector. Our findings show that seemingly immunodominant transgene epitopes can be dominated by Ad-derived epitopes. These findings underline the importance of thorough characterization of vaccine vectors, and modifications of vectors or immunogens may be required to prevent impaired transgene-specific immune responses. Ad-based vectors are widely used in experimental preclinical and clinical immunization studies against numerous infectious agents, such as human immunodeficiency virus, Ebola virus, , or Preexisting immunity to Ad-based vectors is widely recognized as a hindrance to the widespread use of Ad-based vectors for immunizations in humans; however, our data show that an immune response to Ad-derived T cell epitopes can also result in loss or impairment of transgene-specific immune responses in prenaive vaccinees due to immune competition. Our results highlight that seemingly immunodominant epitopes may be affected by dominance of vector-derived epitopes, and modifications of the vector design or the immunogens employed in immunization may lead to more effective vaccines.
[Mh] Termos MeSH primário: Adenoviridae/genética
Linfócitos T CD8-Positivos/imunologia
Epitopos de Linfócito T/imunologia
Epitopos Imunodominantes/imunologia
Transgenes
[Mh] Termos MeSH secundário: Adenoviridae/imunologia
Vacinas contra Adenovirus/imunologia
Animais
Linfócitos T CD8-Positivos/química
Vírus da Leucemia Murina de Friend/genética
Vírus da Leucemia Murina de Friend/imunologia
Vetores Genéticos
Imunização
Interleucina-2/administração & dosagem
Interleucina-2/genética
Interleucina-2/imunologia
Ativação Linfocitária
Camundongos
Retroviridae/genética
Retroviridae/imunologia
Vacinas de DNA/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adenovirus Vaccines); 0 (Epitopes, T-Lymphocyte); 0 (Immunodominant Epitopes); 0 (Interleukin-2); 0 (Vaccines, DNA)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE


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[PMID]:28651002
[Au] Autor:Abraham PR; Pathak N; Pradhan G; Sumanlatha G; Mukhopadhyay S
[Ad] Endereço:Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India.
[Ti] Título:The N-terminal domain of Mycobacterium tuberculosis PPE17 (Rv1168c) protein plays a dominant role in inducing antibody responses in active TB patients.
[So] Source:PLoS One;12(6):e0179965, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The PPE (proline-proline-glutamic acid) proteins of Mycobacterium tuberculosis are characterized by a conserved N-terminal domain of approximately 180 amino acids and variable C-terminal domain. Since last decade, these proteins have gained much importance in the serodiagnosis of tuberculosis (TB) as they act as a source of antigenic variation. We have demonstrated earlier that one of the PPE proteins PPE17 (Rv1168c) induces strong B-cell and T-cell responses in active TB disease and also displays a higher antibody titer compared to immunodominant antigens such as ESAT-6, Hsp60 and PPD. However, the immunodominant domain of PPE17 (N-terminal or C-terminal) was not examined in detail. In the present study, we observed that antibody responses elicited in TB patients were directed mostly towards the N-terminal domain of PPE17 (N-PPE17). The antibody generated against N-PPE17 in TB patients did not significantly cross-react with N-terminal domains of other PPE proteins used in this study. Our data suggest that the N-terminal domain of PPE17 protein is immunodominant and could be used as a better serodiagnostic marker than the full-length PPE17 protein.
[Mh] Termos MeSH primário: Anticorpos Antibacterianos/biossíntese
Antígenos de Bactérias/imunologia
Mycobacterium tuberculosis/imunologia
Tuberculose/imunologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Antígenos de Bactérias/química
Antígenos de Bactérias/genética
Proteínas de Bactérias/química
Proteínas de Bactérias/genética
Proteínas de Bactérias/imunologia
Estudos de Casos e Controles
Reações Cruzadas
Feminino
Seres Humanos
Epitopos Imunodominantes/química
Epitopos Imunodominantes/genética
Masculino
Meia-Idade
Mycobacterium tuberculosis/química
Mycobacterium tuberculosis/genética
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/imunologia
Domínios Proteicos
Testes Sorológicos
Tuberculose/diagnóstico
Tuberculose/microbiologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Bacterial); 0 (Antigens, Bacterial); 0 (Bacterial Proteins); 0 (Immunodominant Epitopes); 0 (Peptide Fragments); 0 (Rv1168c protein, Mycobacterium tuberculosis)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170627
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179965



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