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[PMID]:28922789
[Au] Autor:Mlecnik B; Van den Eynde M; Bindea G; Church SE; Vasaturo A; Fredriksen T; Lafontaine L; Haicheur N; Marliot F; Debetancourt D; Pairet G; Jouret-Mourin A; Gigot JF; Hubert C; Danse E; Dragean C; Carrasco J; Humblet Y; Valge-Archer V; Berger A; Pagès F; Machiels JP; Galon J
[Ad] Endereço:Laboratory of Integrative Cancer Immunology, INSERM, UMRS1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMRS1138, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMRS1138, Centre de Recherche des Cordeliers, Paris, France; Inovarion, Paris, France; Department of Medic
[Ti] Título:Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival.
[So] Source:J Natl Cancer Inst;110(1), 2018 Jan 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: This study assesses how the metastatic immune landscape is impacting the response to treatment and the outcome of colorectal cancer (CRC) patients. Methods: Complete curative resection of metastases (n = 441) was performed for two patient cohorts (n = 153). Immune densities were quantified in the center and invasive margin of all metastases. Immunoscore and T and B cell (TB) score were analyzed in relation to radiological and pathological responses and patient's disease-free (DFS) and overall survival (OS) using multivariable Cox proportional hazards models. All statistical tests were two-sided. Results: The spatial distribution of immune cells within metastases was nonuniform. Patients, as well as metastases of the same patient, had variable immune infiltrates and response to therapy. A beneficial response was statistically significantly associated with increased immune densities. Among all metastases, Immunoscore (I) and TB score evaluated in the least immune-infiltrated metastases were the strongest predictors for DFS and OS (five-year follow-up, Immunoscore: I 3-4: DFS rate = 27.9%, 95% CI = 15.2 to 51.3; vs I 0-1-2: DFS rate = 12.3%, 95% CI = 4.9 to 30.6; HR = 0.45, 95% CI = 0.28 to 0.70, P = .02; I 3-4: OS rate = 64.6%, 95% CI = 46.6 to 89.6; vs I 0-1-2: OS rate = 32.5%, 95% CI = 17.2 to 61.4; HR = 0.32, 95% CI = 0.15 to 0.66, P = .001, C-index = 65.9%; five-year follow-up, TB score: TB 3-4: DFS rate = 25.7%, 95% CI = 14.2 to 46.6; vs TB 0-1-2: DFS rate = 5.0%, 95% CI = 0.8 to 32.4; HR = 0.36, 95% CI = 0.22 to 0.57, P < .001; TB 3-4: OS rate = 63.7%, 95% CI = 46.4 to 87.5; vs TB 0-1-2: OS rate: 21.4%, 95% CI = 9.2 to 49.8; HR = 0.25, 95% CI = 0.12 to 0.51, P < .001, C-index = 67.8%). High TB score and Immunoscore patients had a median survival of 70.5 months, while low patients survived only 25.1 to 38.3 months. Nonresponding patients with high-immune infiltrates had prolonged DFS (HR = 0.28, 95% CI = 0.15 to 0.52, P = .001) and OS (HR = 0.25, 95% CI = 0.1 to 0.62, P = .001). The immune parameters remained the only statistically significant prognostic factor associated with DFS and OS in multivariable analysis (P < .001), while response to treatment was not. Conclusions: Response to treatment and prolonged survival of metastatic CRC patients were statistically significantly associated with high-immune densities quantified into the least immune-infiltrated metastasis.
[Mh] Termos MeSH primário: Linfócitos B
Neoplasias Colorretais/imunologia
Neoplasias Hepáticas/imunologia
Neoplasias Pulmonares/imunologia
Linfócitos do Interstício Tumoral
Linfócitos T
[Mh] Termos MeSH secundário: Idoso
Antígenos CD20/análise
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Linfócitos B/química
Complexo CD3/análise
Linfócitos T CD8-Positivos
Quimioterapia Adjuvante
Neoplasias Colorretais/patologia
Neoplasias Colorretais/terapia
Intervalo Livre de Doença
Seguimentos
Fatores de Transcrição Forkhead/análise
Hepatectomia
Seres Humanos
Antígenos Comuns de Leucócito/análise
Neoplasias Hepáticas/secundário
Neoplasias Hepáticas/terapia
Neoplasias Pulmonares/secundário
Neoplasias Pulmonares/terapia
Contagem de Linfócitos
Metastasectomia
Meia-Idade
Metástase Neoplásica
Pneumonectomia
Período Pré-Operatório
Critérios de Avaliação de Resposta em Tumores Sólidos
Taxa de Sobrevida
Linfócitos T/química
Microambiente Tumoral/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD20); 0 (CD3 Complex); 0 (FOXP3 protein, human); 0 (Forkhead Transcription Factors); EC 3.1.3.48 (Leukocyte Common Antigens)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx123


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[PMID]:28745620
[Au] Autor:Iturri L; Saenz Coronilla J; Lallemand Y; Gomez Perdiguero E
[Ad] Endereço:Department of Developmental and Stem Cell Biology, CNRS UMR3738, Department of Immunology, Institut Pasteur; Cellule Pasteur UPMC, University Pierre et Marie Curie.
[Ti] Título:Identification Of Erythromyeloid Progenitors And Their Progeny In The Mouse Embryo By Flow Cytometry.
[So] Source:J Vis Exp;(125), 2017 Jul 17.
[Is] ISSN:1940-087X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Macrophages are professional phagocytes from the innate arm of the immune system. In steady-state, sessile macrophages are found in adult tissues where they act as front line sentinels of infection and tissue damage. While other immune cells are continuously renewed from hematopoietic stem and progenitor cells (HSPC) located in the bone marrow, a lineage of macrophages, known as resident macrophages, have been shown to be self-maintained in tissues without input from bone marrow HSPCs. This lineage is exemplified by microglia in the brain, Kupffer cells in the liver and Langerhans cells in the epidermis among others. The intestinal and colon lamina propria are the only adult tissues devoid of HSPC-independent resident macrophages. Recent investigations have identified that resident macrophages originate from the extra-embryonic yolk sac hematopoiesis from progenitor(s) distinct from fetal hematopoietic stem cells (HSC). Among yolk sac definitive hematopoiesis, erythromyeloid progenitors (EMP) give rise both to erythroid and myeloid cells, in particular resident macrophages. EMP are only generated within the yolk sac between E8.5 and E10.5 days of development and they migrate to the fetal liver as early as circulation is connected, where they expand and differentiate until at least E16.5. Their progeny includes erythrocytes, macrophages, neutrophils and mast cells but only EMP-derived macrophages persist until adulthood in tissues. The transient nature of EMP emergence and the temporal overlap with HSC generation renders the analysis of these progenitors difficult. We have established a tamoxifen-inducible fate mapping protocol based on expression of the macrophage cytokine receptor Csf1r promoter to characterize EMP and EMP-derived cells in vivo by flow cytometry.
[Mh] Termos MeSH primário: Embrião de Mamíferos/citologia
Citometria de Fluxo/métodos
Células-Tronco/citologia
[Mh] Termos MeSH secundário: Animais
Diferenciação Celular
Células Cultivadas
Desenvolvimento Embrionário/efeitos dos fármacos
Feminino
Antígenos Comuns de Leucócito/metabolismo
Macrófagos/citologia
Macrófagos/metabolismo
Camundongos
Proteínas Proto-Oncogênicas c-kit/metabolismo
Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética
Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/metabolismo
Células-Tronco/metabolismo
Tamoxifeno/farmacologia
Gravação em Vídeo
Saco Vitelino/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Csf1r protein, mouse); 0 (Receptors, Granulocyte-Macrophage Colony-Stimulating Factor); 094ZI81Y45 (Tamoxifen); EC 2.7.10.1 (Proto-Oncogene Proteins c-kit); EC 3.1.3.48 (Leukocyte Common Antigens)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180130
[Lr] Data última revisão:
180130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.3791/55305


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[PMID]:28465358
[Au] Autor:Amankulor NM; Kim Y; Arora S; Kargl J; Szulzewsky F; Hanke M; Margineantu DH; Rao A; Bolouri H; Delrow J; Hockenbery D; Houghton AM; Holland EC
[Ad] Endereço:Department of Neurosurgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
[Ti] Título:Mutant IDH1 regulates the tumor-associated immune system in gliomas.
[So] Source:Genes Dev;31(8):774-786, 2017 04 15.
[Is] ISSN:1549-5477
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Gliomas harboring mutations in isocitrate dehydrogenase 1/2 (IDH1/2) have the CpG island methylator phenotype (CIMP) and significantly longer patient survival time than wild-type IDH1/2 (wtIDH1/2) tumors. Although there are many factors underlying the differences in survival between these two tumor types, immune-related differences in cell content are potentially important contributors. In order to investigate the role of IDH mutations in immune response, we created a syngeneic pair mouse model for mutant IDH1 (muIDH1) and wtIDH1 gliomas and demonstrated that muIDH1 mice showed many molecular and clinical similarities to muIDH1 human gliomas, including a 100-fold higher concentration of 2-hydroxygluratate (2-HG), longer survival time, and higher CpG methylation compared with wtIDH1. Also, we showed that IDH1 mutations caused down-regulation of leukocyte chemotaxis, resulting in repression of the tumor-associated immune system. Given that significant infiltration of immune cells such as macrophages, microglia, monocytes, and neutrophils is linked to poor prognosis in many cancer types, these reduced immune infiltrates in muIDH1 glioma tumors may contribute in part to the differences in aggressiveness of the two glioma types.
[Mh] Termos MeSH primário: Neoplasias Encefálicas/genética
Neoplasias Encefálicas/imunologia
Glioma/genética
Glioma/imunologia
Sistema Imunitário/fisiopatologia
Isocitrato Desidrogenase/genética
Isocitrato Desidrogenase/metabolismo
[Mh] Termos MeSH secundário: Animais
Neoplasias Encefálicas/enzimologia
Quimiotaxia/genética
Metilação de DNA
Modelos Animais de Doenças
Glioma/enzimologia
Seres Humanos
Antígenos Comuns de Leucócito/metabolismo
Leucócitos/patologia
Camundongos
Mutação
Infiltração de Neutrófilos/genética
Neutrófilos/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
EC 1.1.1.41 (Isocitrate Dehydrogenase); EC 3.1.3.48 (Leukocyte Common Antigens)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180130
[Lr] Data última revisão:
180130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1101/gad.294991.116


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[PMID]:28456661
[Au] Autor:Hasby Saad MA; Hasby EA
[Ad] Endereço:Medical Parasitology Department, Tanta Faculty of Medicine, Egypt. Electronic address: m.hasby@yahoo.com.
[Ti] Título:Trichinella Spiralis Impact on Mesenchymal Stem Cells: Immunohistochemical Study by Image Analyzer in Murine Model.
[So] Source:Exp Mol Pathol;102(3):396-407, 2017 06.
[Is] ISSN:1096-0945
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:This study aims to elucidate whether Trichinella spiralis infection or its crude antigen administration can stimulate recruitment of CD105 /CD45 cells that could represent MSCs in intestine and skeletal muscle of experimental BALB/c albino mice compared to healthy control mice. Studied mice were divided into: 20 healthy control, 20 with orally induced T. spiralis infection, 20 received adult worm crude antigen orally and 20 received larval crude antigen intramuscular. According to specific timing schedule, mice were sacrificed and tissue sections were examined for CD105 and CD45 immunohistochemical expression using image J image analyzing software, to compare different study groups. T. spiralis infection induced a significant increase in density of CD105 /CD45 cells that could represent MSCs in both intestinal and muscle sections, similarly the intramuscular injected larval crude antigen caused more infiltration of such cells in muscles compared to muscle sections from healthy control mice. However, no significant difference was noticed in intestinal sections after oral adult crude antigen administration compared to healthy control mice. So, injected T. spiralis crude antigen might be a successful stimulant to MSCs attraction and recruitment in tissues nearby injection site. This could be beneficial for cell regeneration and tissue repair in case of presence of a disease induced damage.
[Mh] Termos MeSH primário: Intestinos/parasitologia
Células Mesenquimais Estromais/citologia
Triquinelose/imunologia
[Mh] Termos MeSH secundário: Animais
Antígenos de Helmintos/administração & dosagem
Movimento Celular
Endoglina/metabolismo
Feminino
Imuno-Histoquímica
Intestinos/imunologia
Larva
Antígenos Comuns de Leucócito/metabolismo
Camundongos
Camundongos Endogâmicos BALB C
Músculo Esquelético/imunologia
Músculo Esquelético/parasitologia
Trichinella spiralis
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Helminth); 0 (Endoglin); EC 3.1.3.48 (Leukocyte Common Antigens)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171214
[Lr] Data última revisão:
171214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


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[PMID]:28982901
[Au] Autor:Zadka L; Kram P; Koscinski J; Jankowski R; Kaczmarek M; Piatek K; Kulus M; Gomulkiewicz A; Piotrowska A; Dziegiel P
[Ad] Endereço:Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland ceadr7@gmail.com.
[Ti] Título:Association Between Interleukin-10 Receptors and the CD45-Immunophenotype of Central Nervous System Tumors: A Preliminary Study.
[So] Source:Anticancer Res;37(10):5777-5783, 2017 10.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: One of the current hypotheses assumes that brain tumors exert an immunosuppressive influence on the surrounding cellular environment. Interleukin-10 (IL-10) is one of the immunosuppressive cytokines modifying the biological activity of cancer. The aim of this study was to assess the expression of IL10R in CD45 cells within primary brain tumors and metastases and establish its association with tumor basic immunophenotype. PATIENTS AND METHODS: Tissue samples were obtained intraoperatively during surgeries of 32 patients suffering from meningiomas (n=9), gliomas (n=12) and metastatic tumors (n=11). Expression was assessed with flow cytometry and immunohistochemical reactions. RESULTS: Expression of IL10R subunits within the leukocyte population (CD45 cells) was significantly higher in primary tumors than in metastases. CONCLUSION: To the best of our knowledge, this is the first study describing a correlation between the IL10R expression on leukocytes and histological types of brain tumors.
[Mh] Termos MeSH primário: Neoplasias Encefálicas/imunologia
Glioma/imunologia
Subunidade alfa de Receptor de Interleucina-10/análise
Subunidade beta de Receptor de Interleucina-10/análise
Antígenos Comuns de Leucócito/análise
Linfócitos do Interstício Tumoral/imunologia
Neoplasias Meníngeas/imunologia
Meningioma/imunologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Biomarcadores Tumorais/análise
Neoplasias Encefálicas/patologia
Neoplasias Encefálicas/cirurgia
Feminino
Citometria de Fluxo
Glioma/patologia
Glioma/cirurgia
Seres Humanos
Imuno-Histoquímica
Imunofenotipagem/métodos
Linfócitos do Interstício Tumoral/patologia
Masculino
Neoplasias Meníngeas/patologia
Neoplasias Meníngeas/cirurgia
Meningioma/patologia
Meningioma/cirurgia
Meia-Idade
Metástase Neoplásica
Fenótipo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (IL10RB protein, human); 0 (Interleukin-10 Receptor alpha Subunit); 0 (Interleukin-10 Receptor beta Subunit); EC 3.1.3.48 (Leukocyte Common Antigens); EC 3.1.3.48 (PTPRC protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171007
[St] Status:MEDLINE


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[PMID]:28855268
[Au] Autor:Haglund F; Hallström BM; Nilsson IL; Höög A; Juhlin CC; Larsson C
[Ad] Endereço:Department of Oncology-PathologyKarolinska Institutet, Cancer Center Karolinska (CCK), Karolinska University Hospital, Stockholm, Sweden Felix.Haglund@ki.se.
[Ti] Título:Inflammatory infiltrates in parathyroid tumors.
[So] Source:Eur J Endocrinol;177(6):445-453, 2017 Dec.
[Is] ISSN:1479-683X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:CONTEXT: Inflammatory infiltrates are sometimes present in solid tumors and may be coupled to clinical behavior or etiology. Infectious viruses contribute to tumorigenesis in a significant fraction of human neoplasias. OBJECTIVE: Characterize inflammatory infiltrates and possible viral transcription in primary hyperparathyroidism. DESIGN: From the period 2007 to 2016, a total of 55 parathyroid tumors (51 adenomas and 4 hyperplasias) with prominent inflammatory infiltrates were identified from more than 2000 parathyroid tumors in the pathology archives, and investigated by immunohistochemistry for CD4, CD8, CD20 and CD45 and scored as +0, +1 or +2. Clinicopathological data were compared to 142 parathyroid adenomas without histological evidence of inflammation. Transcriptome sequencing was performed for 13 parathyroid tumors (four inflammatory, 9 non-inflammatory) to identify potential viral transcripts. RESULTS: Tumors had prominent germinal center-like nodular (+2) lymphocytic infiltrates consisting of T and B lymphocytes (31%) and/or diffuse (+1-2) infiltrates of predominantly CD8+ T lymphocytes (84%). In the majority of cases with adjacent normal parathyroid tissue, the normal rim was unaffected by the inflammatory infiltrates (96%). Presence of inflammatory infiltrates was associated with higher levels of serum-PTH ( = 0.007) and oxyphilic differentiation ( = 0.002). Co-existent autoimmune disease was observed in 27% of patients with inflammatory infiltrates, which in turn was associated with oxyphilic differentiation ( = 0.041). Additionally, prescription of anti-inflammatory drugs was associated with lower serum ionized calcium ( = 0.037). CONCLUSIONS: No evidence of virus-like sequences in the parathyroid tumors could be found by transcriptome sequencing, suggesting that other factors may contribute to attract the immune system to the parathyroid tumor tissue.
[Mh] Termos MeSH primário: Adenoma/imunologia
Linfócitos B/imunologia
Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD8-Positivos/imunologia
Hiperparatireoidismo Primário/imunologia
Glândulas Paratireoides/imunologia
Neoplasias das Paratireoides/imunologia
[Mh] Termos MeSH secundário: Adenoma/metabolismo
Adenoma/patologia
Adenoma/virologia
Antígenos CD20/metabolismo
Linfócitos B/metabolismo
Linfócitos B/patologia
Biomarcadores/metabolismo
Linfócitos T CD4-Positivos/metabolismo
Linfócitos T CD4-Positivos/patologia
Linfócitos T CD8-Positivos/metabolismo
Linfócitos T CD8-Positivos/patologia
Estudos de Coortes
Feminino
Seres Humanos
Hiperparatireoidismo Primário/metabolismo
Hiperparatireoidismo Primário/patologia
Hiperparatireoidismo Primário/virologia
Hiperplasia/imunologia
Hiperplasia/patologia
Imuno-Histoquímica
Antígenos Comuns de Leucócito/metabolismo
Leucócitos/imunologia
Leucócitos/metabolismo
Leucócitos/patologia
Masculino
Meia-Idade
Glândulas Paratireoides/metabolismo
Glândulas Paratireoides/patologia
Glândulas Paratireoides/virologia
Neoplasias das Paratireoides/metabolismo
Neoplasias das Paratireoides/patologia
Neoplasias das Paratireoides/virologia
RNA Viral/metabolismo
Estudos Retrospectivos
Transcrição Genética
Proteínas Virais/genética
Proteínas Virais/metabolismo
Replicação Viral
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD20); 0 (Biomarkers); 0 (RNA, Viral); 0 (Viral Proteins); EC 3.1.3.48 (Leukocyte Common Antigens)
[Em] Mês de entrada:1710
[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:10.1530/EJE-17-0277


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[PMID]:28781259
[Au] Autor:Todosenko NM; Khaziakhmatova OG; Yurova KA; Malinina IP; Litvinova LS
[Ad] Endereço:Immanuel Kant Baltic Federal University.
[Ti] Título:[The influence of methylprednisolone on the ability of CD4+CD95+HLA-DR+ T-cells to produce proinflammatory medators in cultures of TCR-activated CD3+CD45RO+ T-lymphocytes from patients with rheumatoid arthritis].
[Ti] Título:Vliianie metilprednizolona na sposobnost' CD4+CD95+HLA-DR+ T-kletok v kul'turakh TCR-aktivirovannykh CD3+CD45RO+ T-limfotsitov bol'nykh revmatoidnym artritom produtsirovat' provospalitel'nye mediatory..
[So] Source:Biomed Khim;63(3):255-265, 2017 May.
[Is] ISSN:2310-6972
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:The effect of different concentrations of the glucocorticoid (GC) methylprednisolone (MP) on CD4+CD95+HLA-DR+ T-cells and their ability to produce proinflammatory mediators in cultures of TCR-stimulated CD3+CD45RO+ T-lymphocytes in the in vitro system was investigated. T cells were obtained from healthy donors and patients with rheumatoid arthritis (RA).Under conditions of TCR-activation, MP increased the number of CD4+HLA-DR+CD95+ cells in CD3+CD45RO+ cultures obtained from RA patients and did not change their content in the control group. In general, MP decreased production of proinflammatory factors (IFN-, IL-2, IL-17, IL-21 and TNF-) by TCR-activated CD3+CD45RO+ cells from healthy donors and RA, consistent with the overall immunosuppressive mechanism of GC action. The correlation between CD4+CD45RO+HLA-DR+CD95+ T-cell contents and parameters reflecting production of proinflammatory mediators (IL-17, IL-21 and TNF-) in RA patients indicates maintenance of the pro-inflammatory potential of this T-cell population exposed to GC action. We suggest that relative resistance of CD4+CD45RO+CD95+HLA-DR+ T-cells of RA patients to the suppressor effect of GC leads to maintenance and even enhancement in the functional capacities of autoreactive cells in the pathogenesis of RA.
[Mh] Termos MeSH primário: Artrite Reumatoide/imunologia
Linfócitos T CD4-Positivos/efeitos dos fármacos
Regulação da Expressão Gênica/efeitos dos fármacos
Glucocorticoides/farmacologia
Metilprednisolona/farmacologia
[Mh] Termos MeSH secundário: Adulto
Anticorpos/farmacologia
Artrite Reumatoide/patologia
Antígenos CD2/genética
Antígenos CD2/imunologia
Complexo CD3/genética
Complexo CD3/imunologia
Antígenos CD4/genética
Antígenos CD4/imunologia
Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD4-Positivos/patologia
Estudos de Casos e Controles
Feminino
Regulação da Expressão Gênica/imunologia
Antígenos HLA-DR/genética
Antígenos HLA-DR/imunologia
Seres Humanos
Interleucina-17/biossíntese
Interleucina-17/imunologia
Interleucina-2/biossíntese
Interleucina-2/imunologia
Interleucinas/biossíntese
Interleucinas/imunologia
Antígenos Comuns de Leucócito/genética
Antígenos Comuns de Leucócito/imunologia
Ativação Linfocitária
Masculino
Cultura Primária de Células
Transdução de Sinais
Fator de Necrose Tumoral alfa/biossíntese
Fator de Necrose Tumoral alfa/imunologia
Receptor fas/genética
Receptor fas/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies); 0 (CD2 Antigens); 0 (CD3 Complex); 0 (CD4 Antigens); 0 (FAS protein, human); 0 (Glucocorticoids); 0 (HLA-DR Antigens); 0 (Interleukin-17); 0 (Interleukin-2); 0 (Interleukins); 0 (Tumor Necrosis Factor-alpha); 0 (fas Receptor); 0 (interleukin-21); EC 3.1.3.48 (Leukocyte Common Antigens); X4W7ZR7023 (Methylprednisolone)
[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:170808
[St] Status:MEDLINE
[do] DOI:10.18097/PBMC20176303255


  8 / 7722 MEDLINE  
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[PMID]:28763416
[Au] Autor:El-Jawhari JJ; Cuthbert R; McGonagle D; Jones E; Giannoudis PV
[Ad] Endereço:1Leeds Institute of Rheumatic and Musculoskeletal Medicine, St. James Hospital, University of Leeds, Leeds, United Kingdom 2NIHR-Leeds Musculoskeletal Biomedical Research Unit (LMBRU), Chapel Allerton Hospital, University of Leeds, Leeds, United Kingdom 3Clinical Pathology Department, Mansoura University, Mansoura, Egypt.
[Ti] Título:The CD45lowCD271high Cell Prevalence in Bone Marrow Samples May Provide a Useful Measurement of the Bone Marrow Quality for Cartilage and Bone Regenerative Therapy.
[So] Source:J Bone Joint Surg Am;99(15):1305-1313, 2017 Aug 02.
[Is] ISSN:1535-1386
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Bone marrow aspirates and concentrates are increasingly being used for musculoskeletal regenerative therapies, providing bone and cartilage progenitors. However, the quality of these bone marrow samples remains imprecise within clinical settings. As there is a need for the development of these therapies, a method of counting CD45CD271 cells was optimized and tested as an indicator of bone marrow sample quality. METHODS: Bone marrow aspirates were collected from 54 donors (28 male and 26 female; median age of 48 years). The reagent concentrations were optimized for fast staining, and an acoustic-focusing flow cytometer (Attune) was used to enable automated CD45CD271 cell counting in bone marrow aspirates, bone marrow concentrates, and samples loaded onto a collagen scaffold. The CD45CD271 cell counts were compared with those obtained using another flow-cytometry-based method (LSR II) and with connective tissue progenitor (CTP) counts quantified using a colony forming unit-fibroblast (CFU-F) assay. RESULTS: The optimized method enabled the counting of CD45CD271 cells within only 15 minutes. The quantified cell counts (median, 1,520; range, 96 to 20,992 cells/mL of bone marrow) were positively correlated with the CTP counts (p < 0.0001; r = 0.7237). In agreement with CFU-F and LSR II-based assays, the CD45CD271 cell counts quantified using the Attune-based method decreased with age in the samples from female but not male donors (p = 0.0015 and p = 0.3877, respectively). A significant increase in CD45CD271 cell counts was detected following bone marrow concentration (mean, 5-fold; 95% confidence interval [CI], 3.6 to 7.2-fold). Additionally, the number of CD45CD271 cells attached to the collagen scaffold was positively correlated with the number of progenitor cells that survived on the scaffold after 2-week culture (p = 0.0348). CONCLUSIONS: An assay for counting CD45CD271 cells may provide a useful measurement of bone marrow quality. While the specificity of this measurement of CD45CD271 cells remained low in our experimental conditions, CD45CD271 cell counts were positively and modestly correlated with the prevalence of CTPs. CLINICAL RELEVANCE: A fast and automated assessment of bone marrow aspirate/concentrate quality using CD45CD271 cell counting may be a useful tool for improving the quality of regenerative therapy.
[Mh] Termos MeSH primário: Transplante de Medula Óssea/métodos
Regeneração Óssea/fisiologia
Cartilagem/citologia
Antígenos Comuns de Leucócito/análise
Proteínas do Tecido Nervoso/análise
Receptores de Fator de Crescimento Neural/análise
Células-Tronco
[Mh] Termos MeSH secundário: Contagem de Células
Feminino
Citometria de Fluxo
Seres Humanos
Masculino
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (NGFR protein, human); 0 (Nerve Tissue Proteins); 0 (Receptors, Nerve Growth Factor); EC 3.1.3.48 (Leukocyte Common Antigens); EC 3.1.3.48 (PTPRC protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE
[do] DOI:10.2106/JBJS.16.01138


  9 / 7722 MEDLINE  
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[PMID]:28759630
[Au] Autor:Landskron J; Kraggerud SM; Wik E; Dørum A; Bjørnslett M; Melum E; Helland Ø; Bjørge L; Lothe RA; Salvesen HB; Taskén K
[Ad] Endereço:Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway.
[Ti] Título:C77G in PTPRC (CD45) is no risk allele for ovarian cancer, but associated with less aggressive disease.
[So] Source:PLoS One;12(7):e0182030, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The pan lymphocyte marker CD45 exists in various isoforms arising from alternative splicing of the exons 4, 5 and 6. While naïve T cells express CD45RA translated from an mRNA containing exon 4, exons 4-6 are spliced out to encode the shorter CD45R0 in antigen-experienced effector/memory T cells. The SNP C77G (rs17612648) is located in exon 4 and blocks the exon's differential splicing from the pre-mRNA, enforcing expression of CD45RA. Several studies have linked C77G to autoimmune diseases but lack of validation in other cohorts has left its role elusive. An incidental finding in an ovarian cancer patient cohort from West Norway (Bergen region, n = 312), suggested that the frequency of C77G was higher among ovarian cancer patients than in healthy Norwegians (n = 1,357) (3.0% vs. 1.8% allele frequency). However, this finding could not be validated in a larger patient cohort from South-East Norway (Oslo region, n = 1,198) with 1.2% allele frequency. Hence, C77G is not associated with ovarian cancer in the Norwegian population. However, its frequency was increased in patients with FIGO stage II, endometrioid histology or an age at diagnosis of 60 years or older indicating a possible association with a less aggressive cancer type.
[Mh] Termos MeSH primário: Antígenos Comuns de Leucócito/genética
Mutação de Sentido Incorreto
Neoplasias Ovarianas/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Estudos de Casos e Controles
Feminino
Frequência do Gene
Seres Humanos
Meia-Idade
Noruega
Neoplasias Ovarianas/patologia
Polimorfismo de Nucleotídeo Único
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.1.3.48 (Leukocyte Common Antigens); EC 3.1.3.48 (PTPRC protein, human)
[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:170801
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182030


  10 / 7722 MEDLINE  
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[PMID]:28735895
[Au] Autor:Courtney AH; Amacher JF; Kadlecek TA; Mollenauer MN; Au-Yeung BB; Kuriyan J; Weiss A
[Ad] Endereço:Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
[Ti] Título:A Phosphosite within the SH2 Domain of Lck Regulates Its Activation by CD45.
[So] Source:Mol Cell;67(3):498-511.e6, 2017 Aug 03.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The Src Family kinase Lck sets a critical threshold for T cell activation because it phosphorylates the TCR complex and the Zap70 kinase. How a T cell controls the abundance of active Lck molecules remains poorly understood. We have identified an unappreciated role for a phosphosite, Y192, within the Lck SH2 domain that profoundly affects the amount of active Lck in cells. Notably, mutation of Y192 blocks critical TCR-proximal signaling events and impairs thymocyte development in retrogenic mice. We determined that these defects are caused by hyperphosphorylation of the inhibitory C-terminal tail of Lck. Our findings reveal that modification of Y192 inhibits the ability of CD45 to associate with Lck in cells and dephosphorylate the C-terminal tail of Lck, which prevents its adoption of an active open conformation. These results suggest a negative feedback loop that responds to signaling events that tune active Lck amounts and TCR sensitivity.
[Mh] Termos MeSH primário: Antígenos Comuns de Leucócito/metabolismo
Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo
Timócitos/enzimologia
Domínios de Homologia de src
[Mh] Termos MeSH secundário: Animais
Ativação Enzimática
Genótipo
Células HEK293
Seres Humanos
Células Jurkat
Antígenos Comuns de Leucócito/química
Antígenos Comuns de Leucócito/genética
Proteína Tirosina Quinase p56(lck) Linfócito-Específica/química
Proteína Tirosina Quinase p56(lck) Linfócito-Específica/deficiência
Proteína Tirosina Quinase p56(lck) Linfócito-Específica/genética
Camundongos Endogâmicos C57BL
Camundongos Knockout
Modelos Moleculares
Mutação
Fenótipo
Fosforilação
Ligação Proteica
Proteínas Proto-Oncogênicas c-fyn/genética
Proteínas Proto-Oncogênicas c-fyn/metabolismo
Receptores de Antígenos de Linfócitos T/metabolismo
Transdução de Sinais
Timócitos/imunologia
Fatores de Tempo
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Antigen, T-Cell); EC 2.7.10.2 (Fyn protein, mouse); EC 2.7.10.2 (Lymphocyte Specific Protein Tyrosine Kinase p56(lck)); EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn); EC 3.1.3.48 (Leukocyte Common Antigens); EC 3.1.3.48 (PTPRC protein, human); EC 3.1.3.48 (Ptprc protein, mouse)
[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:170725
[St] Status:MEDLINE



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