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[PMID]:29267504
[Au] Autor:Mendes GA; Haag T; Trott G; Rech CGSL; Ferreira NP; Oliveira MC; Kohek MB; Pereira-Lima JFS
[Ad] Endereço:Programa de Pós-Graduação em Patologia, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brasil.
[Ti] Título:Expression of E-cadherin, Slug and NCAM and its relationship to tumor invasiveness in patients with acromegaly.
[So] Source:Braz J Med Biol Res;51(2):e6808, 2017 Dec 11.
[Is] ISSN:1414-431X
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Pituitary adenomas account for 10-15% of primary intracranial tumors. Growth hormone (GH)-secreting adenomas account for 13% of all pituitary adenomas and cause acromegaly. These tumors can be aggressive, invade surrounding structures and are highly recurrent. The objective of this study was to evaluate E-cadherin, Slug and neural cell adhesion molecule (NCAM) expression in GH-secreting pituitary adenomas and its relationship to tumor invasiveness. A cross-sectional study of patients who underwent hypophysectomy due to GH-secreting pituitary adenoma from April 2007 to December 2014 was carried out. The medical records were reviewed to collect clinical data. Immediately after surgery, tumor samples were frozen in liquid nitrogen and stored in a biofreezer at -80°C for assessment of E-cadherin 1 (CDH1), SLUG (SNAI2), and NCAM (NCAM1) by real-time PCR. The samples were fixed in formalin and embedded in paraffin for immunohistochemical analysis of E-cadherin and NCAM. Thirty-five patients with acromegaly were included in the study. Of these, 65.7% had invasive tumors. Immunohistochemically, E-cadherin was expressed in 96.7% of patients, and NCAM in 80% of patients. There was no statistically significant relationship between tumor grade or invasiveness and immunohistochemical expression of these markers. Regarding gene expression, 50% of cases expressed CDH1, none expressed SNAI2, and 53.3% expressed NCAM1. There was no statistically significant relationship between tumor grade or invasiveness and gene expression of CDH1, SNAI2, and NCAM1. The absence of Slug overexpression and of E-cadherin and NCAM suppression suggests that expression of these markers is not associated with tumor invasiveness in GH-secreting pituitary adenomas.
[Mh] Termos MeSH primário: Acromegalia/patologia
Adenoma/patologia
Caderinas/análise
Moléculas de Adesão de Célula Nervosa/análise
Neoplasias Hipofisárias/patologia
Fatores de Transcrição da Família Snail/análise
[Mh] Termos MeSH secundário: Acromegalia/genética
Acromegalia/metabolismo
Adenoma/química
Adenoma/genética
Adolescente
Adulto
Idoso
Biomarcadores Tumorais/análise
Antígeno CD56/análise
Estudos Transversais
Feminino
Expressão Gênica
Seres Humanos
Imuno-Histoquímica
Masculino
Meia-Idade
Gradação de Tumores
Invasividade Neoplásica
Neoplasias Hipofisárias/química
Neoplasias Hipofisárias/genética
Reação em Cadeia da Polimerase em Tempo Real
Estatísticas não Paramétricas
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (CD56 Antigen); 0 (Cadherins); 0 (NCAM1 protein, human); 0 (Neural Cell Adhesion Molecules); 0 (SNAI1 protein, human); 0 (Snail Family Transcription Factors)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE


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[PMID]:29308859
[Au] Autor:Radovic Janosevic D; Popovic J; Krstic M; Tubic-Pavlovic A; Stefanovic M; Pop-Trajkovic S
[Ti] Título:The structure of immunocompetent decidual cells in recurrent missed abortions.
[So] Source:Vojnosanit Pregl;73(4):306-11, 2016 Apr.
[Is] ISSN:0042-8450
[Cp] País de publicação:Serbia
[La] Idioma:eng
[Ab] Resumo:Background/Aim: Recurrent or habitual missed abortions (RMA) are defined as three or more consecutive abortions. In the first trimester of pregnancy habitual missed abortions occur in about 1% of population. The aim of this immunohistochemical study of decidua in RMA of unknown etiology was to identify subpopulations of decidual lymphocytes in recurrent miscarriages and compare the distribution of immunocompetent cells in artificial abortions and RMA. Methods. The study included 30 women with at least 2 consecutive miscarriages in the first trimester of pregnancy. Curettements of the third missed abortion were immunohistochemically analyzed. The control group consisted of 20 women without loaded reproductive anamnesis, with the abortion for social reasons. Criteria for exclusion from the study were diagnosed uterine anomalies, positive screening for thrombophilia and women who suffered from diabetes mellitus and disorders in the function of the thyroid gland. Immunophenotyping was performed by immuno-alkaline phosphatase (APAAP) using monoclonal antibodies: CD 30, CD 45 RO, CD 56 and CD 57, CD 68. Methods: The number of missed abortions (1,223) was on the average 9.7% of all deliveriies during the test period. Among them RMA were registered in 52 (4.2%) patients and in 30 (57%) the exact etiology of abortions was not determined. RMA was most common in the 25-34 years of age group. The largest number of RMA showed the ultrasound characteristics of missed abortion in 60% of cases and was in nulliparous patients (76.7%). The number of NK CD56 positive cells did not differ significantly between the types of abortion. In the decidual tissue, a number of NK CD57 positive cells was significantly higher in missed abortions compared to artificial interruptions (p < 0.01). In artificial termination of pregnancy there was an absolute predominance of CD45RO lymphocyte subpopulations, whereas in the RMA group there was slightly greater predominance of CD30 positive cells. The completed analysis showed a significantly higher number of CD68 positive macrophages in a decidual tissue of RMA pregnancy (p < 0.01). Results: The number and phenotypic structure of NK cells are significantly different in normal pregnancy decidua and in RMA. The NK cell dominance is present in the RMA group, in favor of CD56+ and CD 57 of subpopulations with increased CD30 of T lymphocyte subpopulations. Macrophages are more numerous in the decidua of pregnancies ended in abortion, so the cause to RMA of unknown etiology in a number of cases could be disregulation of immunocompetent cells.
[Mh] Termos MeSH primário: Aborto Retido/imunologia
Decídua/imunologia
Decídua/metabolismo
Células Matadoras Naturais/imunologia
[Mh] Termos MeSH secundário: Aborto Retido/metabolismo
Adulto
Antígeno CD56
Antígenos CD57
Feminino
Seres Humanos
Imuno-Histoquímica
Imunofenotipagem
Antígeno Ki-1
Células Matadoras Naturais/classificação
Células Matadoras Naturais/metabolismo
Gravidez
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CD56 Antigen); 0 (CD57 Antigens); 0 (Ki-1 Antigen); 0 (NCAM1 protein, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE
[do] DOI:10.2298/VSP141226018R


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[PMID]:29390581
[Au] Autor:Grushchak S; Joy C; Gray A; Opel D; Speiser J; Reserva J; Tung R; Smith SE
[Ti] Título:Novel treatment of blastic plasmacytoid dendritic cell neoplasm: A case report.
[So] Source:Medicine (Baltimore);96(51):e9452, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Blastic plasmacytoid dendritic cell neoplasm (BPDCN), derived from precursors of plasmacytoid dendritic cells, is a rare and aggressive malignancy with frequent cutaneous involvement. Although cutaneous lesions are often chemosensitive, BPDCN portends a poor prognosis as most patients relapse after developing drug resistance. PATIENT CONCERNS: We report a case of a 65-year-old man who presented with a rapidly enlarging hyperpigmented plaque on his shoulder with subsequent similarly appearing macules and plaques on his chest, back, and neck. DIAGNOSIS: Skin biopsy revealed a dense adnexocentric dermal infiltrate of immature blastoid cells without epidermal involvement. The infiltrate was immunoreactive for CD4, CD56, CD123, and Bcl-2, but negative for CD3, CD8, CD30, MPO, EBER, and ISH. The patient was diagnosed with BPDCN based on these cell markers. INTERVENTION: Bone marrow biopsy and radiologic work-up showed no evidence of extracutaneous involvement. The patient attained partial remission after undergoing 2 rounds of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP regimen) before autologous stem cell transplantation, however, he quickly relapsed and developed new cutaneous lesions. OUTCOMES: The patient was treated with venetoclax, a Bcl-2 inhibitor, and exhibits complete resolution of prior skin findings and continues to remain free of new cutaneous lesions 10 months posttreatment initiation with venetoclax. LESSONS: Herein, we present a case that supports the use of venetoclax, a Bcl-2 inhibitor, in the off-label treatment of BPDCN with Bcl-2 overexpression. Only 1 prior case has reported the off-label use of venetoclax for the treatment of BPDCN. This case highlights a novel therapeutic option for BPDCN patients unresponsive to traditional treatment.
[Mh] Termos MeSH primário: Células Dendríticas/patologia
Neoplasias Cutâneas/diagnóstico
[Mh] Termos MeSH secundário: Idoso
Antígenos CD4/metabolismo
Antígeno CD56/metabolismo
Seres Humanos
Masculino
Pele/citologia
Pele/patologia
Neoplasias Cutâneas/patologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CD4 Antigens); 0 (CD56 Antigen)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009452


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[PMID]:29307521
[Au] Autor:Han W; Ni Q; Liu K; Yao Y; Zhao D; Liu X; Chen Y
[Ad] Endereço:Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou 310003, China; Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, 79 Qingchun Road, Hangzhou 310003, China.
[Ti] Título:Decreased CD122 on CD56 NK associated with its impairment in asymptomatic chronic HBV carriers with high levels of HBV DNA, HBsAg and HBeAg.
[So] Source:Life Sci;195:53-60, 2018 Feb 15.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: NK cells play important roles in inhibiting HBV replication and preventing HBV infection. However, NK-cell dysfunction has not been fully studied in asymptomatic chronic HBV carriers (ASC). This study aims to assess decreased expression of CD122 associated with impaired NK cells and the restoration of NK cells with IL-2 and IL-15 stimulation. MAIN METHODS: The experiments were performed by flow cytometer, cytotoxicity assay, ELISA and western blotting. KEY FINDINGS: The reduced CD122 on CD56 NK cells and CD56 NK cells is associated with high levels of HBV DNA, HBsAg or HBeAg in ASCs, in which CD56 NK-cell impairment is observed. Moreover, decreased IFN-γ and degranulation and low cytotoxicity by CD56 NK cells after CD122 blockade were revealed. IL-2 and/or IL-15 can restore impaired CD56 NK cells, together with increased p-STAT5, which can be reversed by CD122 blockade. Additionally, IL-2 or IL-15 can enhance IFN-α2-activated CD56 NK-cell immune responses via up-regulating interferon alpha and beta receptor subunit 2 (IFNAR2). SIGNIFICANCE: Down-regulated CD122 on CD56 NK cell in ASCs with massive viral antigens and high viremia is associated with its impairment, which can be restored by IL-2 and/or IL-15, or combined with IFN-α2.
[Mh] Termos MeSH primário: Antígeno CD56/biossíntese
DNA Viral/biossíntese
Antígenos de Superfície da Hepatite B/sangue
Antígenos E da Hepatite B/sangue
Vírus da Hepatite B/metabolismo
Hepatite B/metabolismo
Subunidade beta de Receptor de Interleucina-2/biossíntese
Células Matadoras Naturais/metabolismo
[Mh] Termos MeSH secundário: Adulto
Antígeno CD56/genética
Portador Sadio
DNA Viral/genética
Feminino
Vírus da Hepatite B/genética
Seres Humanos
Interferon gama/biossíntese
Interleucina-15/farmacologia
Interleucina-2/farmacologia
Subunidade beta de Receptor de Interleucina-2/genética
Masculino
Receptor de Interferon alfa e beta/biossíntese
Receptor de Interferon alfa e beta/genética
Fator de Transcrição STAT5/biossíntese
Fator de Transcrição STAT5/genética
Viremia/sangue
Viremia/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CD56 Antigen); 0 (DNA, Viral); 0 (Hepatitis B Surface Antigens); 0 (Hepatitis B e Antigens); 0 (IFNAR2 protein, human); 0 (Interleukin-15); 0 (Interleukin-2); 0 (Interleukin-2 Receptor beta Subunit); 0 (STAT5 Transcription Factor); 156986-95-7 (Receptor, Interferon alpha-beta); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE


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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]:28837583
[Au] Autor:An X; Sendra VG; Liadi I; Ramesh B; Romain G; Haymaker C; Martinez-Paniagua M; Lu Y; Radvanyi LG; Roysam B; Varadarajan N
[Ad] Endereço:Department of Chemical and Biomolecular Engineering, University of Houston, Houston, Texas, United States of America.
[Ti] Título:Single-cell profiling of dynamic cytokine secretion and the phenotype of immune cells.
[So] Source:PLoS One;12(8):e0181904, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Natural killer (NK) cells are a highly heterogeneous population of innate lymphocytes that constitute our first line of defense against several types of tumors and microbial infections. Understanding the heterogeneity of these lymphocytes requires the ability to integrate their underlying phenotype with dynamic functional behaviors. We have developed and validated a single-cell methodology that integrates cellular phenotyping and dynamic cytokine secretion based on nanowell arrays and bead-based molecular biosensors. We demonstrate the robust passivation of the polydimethylsiloxane (PDMS)-based nanowells arrays with polyethylene glycol (PEG) and validated our assay by comparison to enzyme-linked immunospot (ELISPOT) assays. We used numerical simulations to optimize the molecular density of antibodies on the surface of the beads as a function of the capture efficiency of cytokines within an open-well system. Analysis of hundreds of individual human peripheral blood NK cells profiled ex vivo revealed that CD56dimCD16+ NK cells are immediate secretors of interferon gamma (IFN-γ) upon activation by phorbol 12-myristate 13-acetate (PMA) and ionomycin (< 3 h), and that there was no evidence of cooperation between NK cells leading to either synergistic activation or faster IFN-γ secretion. Furthermore, we observed that both the amount and rate of IFN-γ secretion from individual NK cells were donor-dependent. Collectively, these results establish our methodology as an investigational tool for combining phenotyping and real-time protein secretion of individual cells in a high-throughput manner.
[Mh] Termos MeSH primário: Citocinas/secreção
Imunofenotipagem
Células Matadoras Naturais/imunologia
[Mh] Termos MeSH secundário: Antígeno CD56/imunologia
Dimetilpolisiloxanos
Ensaio de Imunoadsorção Enzimática
Proteínas Ligadas por GPI/imunologia
Seres Humanos
Células Matadoras Naturais/efeitos dos fármacos
Receptores de IgG/imunologia
Análise de Célula Única
Acetato de Tetradecanoilforbol/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CD56 Antigen); 0 (Cytokines); 0 (Dimethylpolysiloxanes); 0 (FCGR3B protein, human); 0 (GPI-Linked Proteins); 0 (NCAM1 protein, human); 0 (Receptors, IgG); 63148-62-9 (baysilon); NI40JAQ945 (Tetradecanoylphorbol Acetate)
[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:170825
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181904


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[PMID]:28784848
[Au] Autor:Jensen H; Potempa M; Gotthardt D; Lanier LL
[Ad] Endereço:Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143; and.
[Ti] Título:Cutting Edge: IL-2-Induced Expression of the Amino Acid Transporters SLC1A5 and CD98 Is a Prerequisite for NKG2D-Mediated Activation of Human NK Cells.
[So] Source:J Immunol;199(6):1967-1972, 2017 Sep 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Priming of human NK cells with IL-2 is necessary to render them functionally competent upon NKG2D engagement. We examined the underlying mechanisms that control NKG2D responsiveness in NK cells and found that IL-2 upregulates expression of the amino acid transporters SLC1A5 and CD98. Using specific inhibitors to block SLC1A5 and CD98 function, we found that production of IFN-γ and degranulation by CD56 and CD56 NK cells following NKG2D stimulation were dependent on both transporters. IL-2 priming increased the activity of mTORC1, and inhibition of mTORC1 abrogated the ability of the IL-2-primed NK cells to produce IFN-γ in response to NKG2D-mediated stimulation. This study identifies a series of IL-2-induced cellular changes that regulates the NKG2D responsiveness in human NK cells.
[Mh] Termos MeSH primário: Sistema ASC de Transporte de Aminoácidos/metabolismo
Proteína-1 Reguladora de Fusão/metabolismo
Células Matadoras Naturais/fisiologia
Antígenos de Histocompatibilidade Menor/metabolismo
[Mh] Termos MeSH secundário: Sistema ASC de Transporte de Aminoácidos/genética
Antígeno CD56/metabolismo
Células Cultivadas
Citotoxicidade Imunológica
Seres Humanos
Interferon gama/metabolismo
Interleucina-2/imunologia
Interleucina-2/metabolismo
Ativação Linfocitária
Alvo Mecanístico do Complexo 1 de Rapamicina
Antígenos de Histocompatibilidade Menor/genética
Complexos Multiproteicos/antagonistas & inibidores
Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo
Serina-Treonina Quinases TOR/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acid Transport System ASC); 0 (CD56 Antigen); 0 (Fusion Regulatory Protein-1); 0 (Interleukin-2); 0 (KLRK1 protein, human); 0 (Minor Histocompatibility Antigens); 0 (Multiprotein Complexes); 0 (NK Cell Lectin-Like Receptor Subfamily K); 0 (SLC1A5 protein, human); 82115-62-6 (Interferon-gamma); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
[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:170809
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1700497


  8 / 2873 MEDLINE  
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[PMID]:28767726
[Au] Autor:Mahapatra S; Mace EM; Minard CG; Forbes LR; Vargas-Hernandez A; Duryea TK; Makedonas G; Banerjee PP; Shearer WT; Orange JS
[Ad] Endereço:Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, United States of America.
[Ti] Título:High-resolution phenotyping identifies NK cell subsets that distinguish healthy children from adults.
[So] Source:PLoS One;12(8):e0181134, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Natural killer (NK) cells are critical in immune defense against infected, stressed or transformed cells. Their function is regulated by the heterogeneous expression of a wide array of surface receptors that shape its phenotypic diversity. Although NK cells develop in the bone marrow and secondary lymphoid tissues, substantive differentiation is apparent in the peripheral blood including known age-related variation. In order to gain greater insight into phenotypic and functional variation within peripheral blood NK cells across age groups, we used multi-parametric, polyfunctional flow cytometry to interrogate the NK cell variability in 20 healthy adults and 15 5-10, 11-15 and 16-20 year-old children. We found that the normative ranges in both adults and children displayed great inter-individual variation for most markers. While the expression of several receptors did not differ, among those that did, the majority of the differences existed between adults and the three pediatric groups, rather than among children of different ages. Interestingly, we also identified variation in the individual expression of some markers by sex and ethnicity. Combinatorial analysis of NK cell receptors revealed intermediate subsets between the CD56bright and CD56dim NK cells. Furthermore, on examining the NK cell diversity by age, adults were discovered to have the lowest developmental diversity. Thus, our findings identify previously unappreciated NK cell subsets potentially distinguishing children from adults and suggest functional correlates that may have relevance in age-specific host defense.
[Mh] Termos MeSH primário: Imunofenotipagem
Células Matadoras Naturais/metabolismo
[Mh] Termos MeSH secundário: Adolescente
Adulto
Fatores Etários
Antígeno CD56/metabolismo
Criança
Análise por Conglomerados
Feminino
Citometria de Fluxo
Seres Humanos
Células Matadoras Naturais/citologia
Células Matadoras Naturais/imunologia
Leucócitos Mononucleares/citologia
Meia-Idade
Receptores de Células Matadoras Naturais/metabolismo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CD56 Antigen); 0 (Receptors, Natural Killer Cell)
[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:170803
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181134


  9 / 2873 MEDLINE  
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[PMID]:28760868
[Au] Autor:Werneburg S; Fuchs HLS; Albers I; Burkhardt H; Gudi V; Skripuletz T; Stangel M; Gerardy-Schahn R; Hildebrandt H
[Ad] Endereço:Institute of Clinical Biochemistry, and.
[Ti] Título:Polysialylation at Early Stages of Oligodendrocyte Differentiation Promotes Myelin Repair.
[So] Source:J Neurosci;37(34):8131-8141, 2017 Aug 23.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Polysialic acid is a glycan modification of the neural cell adhesion molecule (NCAM) produced by the polysialyltransferases ST8SIA2 and ST8SIA4. Polysialic acid has been detected in multiple sclerosis plaques, but its beneficial or adverse role in remyelination is elusive. Here, we show that, despite a developmental delay, myelination at the onset and during cuprizone-induced demyelination was unaffected in male or mice. However, remyelination, restoration of oligodendrocyte densities, and motor recovery after the cessation of cuprizone treatment were compromised. Impaired differentiation of NCAM- or ST8SIA2-negative oligodendrocyte precursors suggested an underlying cell-autonomous mechanism. In contrast, premature differentiation in ST8SIA4-negative cultures explained the accelerated remyelination previously observed in mice. mRNA profiling during differentiation of human stem cell-derived and primary murine oligodendrocytes indicated that the opposing roles of ST8SIA2 and ST8SIA4 arise from sequential expression. We also provide evidence that potentiation of ST8SIA2 by 9- retinoic acid and artificial polysialylation of oligodendrocyte precursors by a bacterial polysialyltransferase are mechanisms to promote oligodendrocytic differentiation. Thus, differential targeting of polysialyltransferases and polysialic acid engineering are promising strategies to advance the treatment of demyelinating diseases. The beneficial or adverse role of polysialic acid (polySia) in myelin repair is a long-standing question. As a modification of the neural cell adhesion molecule (NCAM), polySia is produced by the polysialyltransferases ST8SIA2 and ST8SIA4. Here we demonstrate that NCAM and ST8SIA2 promote oligodendrocyte differentiation and myelin repair as well as motor recovery after cuprizone-induced demyelination. In contrast, ST8SIA4 delays oligodendrocyte differentiation, explaining its adverse role in remyelination. These opposing roles of the polysialyltransferases are based on different expression profiles. 9- retinoic acid enhances ST8SIA2 expression, providing a mechanism for understanding how it supports oligodendrocyte differentiation and remyelination. Furthermore, artificial polysialylation of the cell surface promotes oligodendrocyte differentiation. Thus, boosting ST8SIA2 and engineering of polySia are promising strategies for improving myelin repair.
[Mh] Termos MeSH primário: Antígeno CD56/biossíntese
Diferenciação Celular/fisiologia
Bainha de Mielina/metabolismo
Oligodendroglia/metabolismo
Sialiltransferases/biossíntese
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Doenças Desmielinizantes/metabolismo
Células-Tronco Embrionárias/metabolismo
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Atividade Motora/fisiologia
Molécula L1 de Adesão de Célula Nervosa
Distribuição Aleatória
Ácidos Siálicos/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CD56 Antigen); 0 (Ncam1 protein, mouse); 0 (Neural Cell Adhesion Molecule L1); 0 (Sialic Acids); 0 (polysialic acid); 0 (polysialyl neural cell adhesion molecule); EC 2.4.99.- (CMP-N-acetylneuraminate-poly-alpha-2,8-sialosyl sialyltransferase); EC 2.4.99.- (Sialyltransferases); EC 2.4.99.8 (ST8SiaIV 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:170802
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.1147-17.2017


  10 / 2873 MEDLINE  
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[PMID]:28719469
[Au] Autor:Rooper LM; Sharma R; Li QK; Illei PB; Westra WH
[Ad] Endereço:Departments of *Pathology †Oncology ‡Otolaryngology, The Johns Hopkins University School of Medicine, Baltimore, MD.
[Ti] Título:INSM1 Demonstrates Superior Performance to the Individual and Combined Use of Synaptophysin, Chromogranin and CD56 for Diagnosing Neuroendocrine Tumors of the Thoracic Cavity.
[So] Source:Am J Surg Pathol;41(11):1561-1569, 2017 Nov.
[Is] ISSN:1532-0979
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Despite the importance of recognizing neuroendocrine differentiation when diagnosing tumors of the thoracic cavity, the sensitivity of traditional neuroendocrine markers is suboptimal, particularly for high-grade neuroendocrine carcinomas such as small cell lung carcinoma and large cell neuroendocrine carcinoma. To increase sensitivity, neuroendocrine markers are routinely ordered as panels of multiple immunostains where any single positive marker is regarded as sufficient evidence of neuroendocrine differentiation. Insulinoma-associated protein 1 (INSM1) is a well-validated transcription factor of neuroendocrine differentiation that has only recently been evaluated for diagnostic use. We performed INSM1 immunohistochemistry on a large series of thoracic neuroendocrine and non-neuroendocrine tumors and compared its performance to synaptophysin, chromogranin, and CD56. INSM1 was positive in 94.9% of small cell lung carcinomas and 91.3% of large cell neuroendocrine carcinomas, compared with 74.4% and 78.3% with the combined panel of traditional markers. INSM1 also stained all (100%) of the atypical carcinoids, typical carcinoids and mediastinal paragangliomas, but only 3.3% of adenocarcinomas and 4.2% of squamous cell carcinomas. Overall, INSM1 demonstrated a sensitivity of 96.4% across all grades of thoracic neuroendocrine tumors, significantly more than the 87.4% using the panel of traditional markers (P=0.02). INSM1 is sufficiently sensitive and specific to serve as a standalone first-line marker of neuroendocrine differentiation. A more restrained approach to immunohistochemical analysis of small thoracic biopsies is appropriate given the expanding demand on this limited material for therapeutic biomarker analysis.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/análise
Antígeno CD56/análise
Carcinoma Neuroendócrino/química
Cromograninas/análise
Imuno-Histoquímica
Proteínas Repressoras/análise
Sinaptofisina/análise
Neoplasias Torácicas/química
[Mh] Termos MeSH secundário: Biópsia
Carcinoma Neuroendócrino/patologia
Diferenciação Celular
Diagnóstico Diferencial
Seres Humanos
Gradação de Tumores
Valor Preditivo dos Testes
Neoplasias Torácicas/patologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (CD56 Antigen); 0 (Chromogranins); 0 (NCAM1 protein, human); 0 (Repressor Proteins); 0 (SYP protein, human); 0 (Synaptophysin); 147955-03-1 (INSM1 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:170719
[St] Status:MEDLINE
[do] DOI:10.1097/PAS.0000000000000916



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