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[PMID]:29267508
[Au] Autor:Wu J; Wang Y; Liu G; Jia Y; Yang J; Shi J; Dong J; Wei J; Liu X
[Ad] Endereço:College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, China.
[Ti] Título:Characterization of air-liquid interface culture of A549 alveolar epithelial cells.
[So] Source:Braz J Med Biol Res;51(2):e6950, 2017 Dec 11.
[Is] ISSN:1414-431X
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Alveolar epithelia play an essential role in maintaining the integrity and homeostasis of lungs, in which alveolar epithelial type II cells (AECII) are a cell type with stem cell potential for epithelial injury repair and regeneration. However, mechanisms behind the physiological and pathological roles of alveolar epithelia in human lungs remain largely unknown, partially owing to the difficulty of isolation and culture of primary human AECII cells. In the present study, we aimed to characterize alveolar epithelia generated from A549 lung adenocarcinoma cells that were cultured in an air-liquid interface (ALI) state. Morphological analysis demonstrated that A549 cells could reconstitute epithelial layers in ALI cultures as evaluated by histochemistry staining and electronic microscopy. Immunofluorescent staining further revealed an expression of alveolar epithelial type I cell (AECI) markers aquaporin-5 protein (AQP-5), and AECII cell marker surfactant protein C (SPC) in subpopulations of ALI cultured cells. Importantly, molecular analysis further revealed the expression of AQP-5, SPC, thyroid transcription factor-1, zonula occludens-1 and Mucin 5B in A549 ALI cultures as determined by both immunoblotting and quantitative RT-PCR assay. These results suggest that the ALI culture of A549 cells can partially mimic the property of alveolar epithelia, which may be a feasible and alternative model for investigating roles and mechanisms of alveolar epithelia in vitro.
[Mh] Termos MeSH primário: Células A549/fisiologia
Células Epiteliais Alveolares/fisiologia
Técnicas de Cultura de Células/métodos
Meios de Cultivo Condicionados
[Mh] Termos MeSH secundário: Análise de Variância
Aquaporina 5/análise
Contagem de Células
Seres Humanos
Immunoblotting
Microscopia Eletrônica de Varredura
Mucina-5B/análise
Proteína C Associada a Surfactante Pulmonar/análise
Reação em Cadeia da Polimerase em Tempo Real
Valores de Referência
Reprodutibilidade dos Testes
Fator Nuclear 1 de Tireoide/análise
Fatores de Tempo
Proteína da Zônula de Oclusão-1/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aquaporin 5); 0 (Culture Media, Conditioned); 0 (Mucin-5B); 0 (NKX2-1 protein, human); 0 (Pulmonary Surfactant-Associated Protein C); 0 (Thyroid Nuclear Factor 1); 0 (Zonula Occludens-1 Protein)
[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


  2 / 1151 MEDLINE  
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[PMID]:29305861
[Au] Autor:Jeong B; Kim HR; Choi NS; Park BS; Eom H; Park JW; Kim JG; Lee BJ
[Ad] Endereço:Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan 44610, South Korea.
[Ti] Título:Role of thyroid transcription factor-1 in transcriptional regulation of heme oxygenase-1.
[So] Source:Biochem Biophys Res Commun;496(1):147-152, 2018 01 29.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Here, we report thyroid transcription factor 1 (TTF-1) as an important transcription factor for the expression of heme oxygenase-1 (HO-1). HO-1 is a well-known cytoprotective enzyme against inflammation. We observed that HO-1 co-expressed with TTF-1 in mouse hypothalamic cells. Results from luciferase and chromatin immunoprecipitation assays revealed that TTF-1 directly activated HO-1 transcription by binding to binding domains in the 5'-flanking region of the HO-1 gene. A proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α), induced nuclear translocation of TTF-1 and increased binding affinity of TTF-1 to its binding sites on the HO-1 gene. HO-1 mRNA increased with TTF-1 overexpression but decreased with RNA interference of TTF-1 expression in rat astroglial C6 cells. Together with results showing involvement of TTF-1 in the TNF-α-induced increase in interleukin 1 beta and monocyte chemotactic protein 1 production, this study suggests that TTF-1 plays an important role in the mouse hypothalamus TNF-α-induced inflammatory response for regulating HO-1 gene expression.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica/fisiologia
Heme Oxigenase-1/metabolismo
Hipotálamo/metabolismo
Proteínas de Membrana/metabolismo
Fator Nuclear 1 de Tireoide/metabolismo
Ativação Transcricional/fisiologia
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Membrane Proteins); 0 (Thyroid Nuclear Factor 1); EC 1.14.14.18 (Heme Oxygenase-1); EC 1.14.14.18 (Hmox1 protein, mouse)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180107
[St] Status:MEDLINE


  3 / 1151 MEDLINE  
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[PMID]:29381996
[Au] Autor:Zhang WL; Ma S; Havrilla L; Cai L; Yu CQ; Shen S; Xu HT; Wang L; Yu JH; Lin XY; Wang E; Yang LH
[Ad] Endereço:Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University.
[Ti] Título:Primary thyroid-like low-grade nasopharyngeal papillary adenocarcinoma: A case report and literature review.
[So] Source:Medicine (Baltimore);96(47):e8851, 2017 Nov.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Primary thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA) is an extremely rare malignant nasopharyngeal tumor with features resembling papillary thyroid carcinoma including nuclear positive expression of thyroid transcription factor-1 (TTF-1). PATIENT CONCERNS: A 64-year-old male presented with nasal bleeding and a foreign body sensation of the nasopharynx. Laryngoscopy revealed a 2.0-cm broad-based mass with a smooth surface on the posterior wall of the nasopharynx. A biopsy was obtained. DIAGNOSES: Histopathologic examination demonstrated tumor cells arranged in both papillary and glandular architecture. The tumor cells express nuclear immunoreactivity for TTF-1. The diagnosis of TL-LGNPPA was made. INTERVENTIONS: After the patient was diagnosed with TL-LGNPPA, he underwent complete surgical resection. OUTCOMES: There was no recurrence or evidence of metastatic disease at the 12-month follow-up. LESSONS: TL-LGNPPA is easy to misdiagnose as metastatic papillary thyroid carcinoma or other relative primary adenocarcinomas. It is important to have a broad differential diagnosis and know the key features of each entity because the prognosis and clinical treatment of each may differ.
[Mh] Termos MeSH primário: Adenocarcinoma Papilar/patologia
Neoplasias Nasofaríngeas/patologia
[Mh] Termos MeSH secundário: Adenocarcinoma Papilar/diagnóstico
Carcinoma Papilar/diagnóstico
Diagnóstico Diferencial
Seres Humanos
Imuno-Histoquímica
Masculino
Meia-Idade
Neoplasias Nasofaríngeas/diagnóstico
Nasofaringe/patologia
Neoplasias da Glândula Tireoide/diagnóstico
Fator Nuclear 1 de Tireoide/metabolismo
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Thyroid Nuclear Factor 1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008851


  4 / 1151 MEDLINE  
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[PMID]:28455095
[Au] Autor:Wang F; Liu C; Jia X; Liu X; Xu Y; Yan S; Jia X; Huang Z; Liu S; Gu M
[Ad] Endereço:Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China; Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China.
[Ti] Título:Next-generation sequencing of NKX2.1, FOXE1, PAX8, NKX2.5, and TSHR in 100 Chinese patients with congenital hypothyroidism and athyreosis.
[So] Source:Clin Chim Acta;470:36-41, 2017 Jul.
[Is] ISSN:1873-3492
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The abnormal expression of certain transcription factors (NKX2.1, FOXE1, NKX2.5, and PAX8) and thyroid stimulating hormone receptor (TSHR) genes has been associated with athyreosis, which is a form of thyroid dysgenesis (TD). We aimed to identify candidate gene mutations in CH patients with athyreosis and to establish the genotype-phenotype correlations in a Chinese population. METHODS: The exons and flanking sequences of NKX2.1, FOXE1, NKX2.5, PAX8, and TSHR were screened by next-generation sequencing and further confirmed by direct Sanger sequencing. The mutation frequencies were calculated and compared against databases. The relationship between genotype and phenotype was also determined. RESULTS: Seven variants were detected in TSHR-p.P52T, p.G132R, p.M164K, p.R450H, p.C700E, p.A522V, and p.R528S. The p. G132R, p. M164K and p. R528S variants were first identified in public databases. Five variants (p.G44D, p.G360V, p.R401Q, p.L418I, and p.E453Q) were found in NKX2.1 and one variant (p.P243T) was detected in FOXE1. In addition, one variant (p.N291I) was found in NKX2.5 and two variants (p.A355V and c.-26G>A) were detected in PAX8. CONCLUSIONS: Our study indicated that TSHR mutations have phenotypic variability and has further expanded the mutation spectrum of TSHR. We also revealed that the rate of NKX2.1, FOXE1, NKX2.5, and PAX8 mutations were low in patients with CH and athyreosis, in contrast to the higher rate of TSHR mutations.
[Mh] Termos MeSH primário: Grupo com Ancestrais do Continente Asiático/genética
Hipotireoidismo Congênito/genética
Análise Mutacional de DNA
Sequenciamento de Nucleotídeos em Larga Escala
Receptores da Tireotropina/genética
Disgenesia da Tireoide/genética
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Sequência de Bases
Criança
Pré-Escolar
Feminino
Fatores de Transcrição Forkhead/genética
Genótipo
Proteína Homeobox Nkx-2.5/genética
Seres Humanos
Masculino
Fator de Transcrição PAX8/genética
Fenótipo
Glândula Tireoide/metabolismo
Fator Nuclear 1 de Tireoide/genética
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (FOXE1 protein, human); 0 (Forkhead Transcription Factors); 0 (Homeobox Protein Nkx-2.5); 0 (NKX2-1 protein, human); 0 (NKX2-5 protein, human); 0 (PAX8 Transcription Factor); 0 (PAX8 protein, human); 0 (Receptors, Thyrotropin); 0 (Thyroid Nuclear Factor 1); 0 (Transcription Factors)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


  5 / 1151 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


  6 / 1151 MEDLINE  
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[PMID]:28833459
[Au] Autor:Casalia ML; Howard MA; Baraban SC
[Ad] Endereço:Epilepsy Research Laboratory, Department of Neurological Surgery and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA.
[Ti] Título:Persistent seizure control in epileptic mice transplanted with gamma-aminobutyric acid progenitors.
[So] Source:Ann Neurol;82(4):530-542, 2017 Oct.
[Is] ISSN:1531-8249
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: A significant proportion of the more than 50 million people worldwide currently suffering with epilepsy are resistant to antiepileptic drugs (AEDs). As an alternative to AEDs, novel therapies based on cell transplantation offer an opportunity for long-lasting modification of epileptic circuits. To develop such a treatment requires careful preclinical studies in a chronic epilepsy model featuring unprovoked seizures, hippocampal histopathology, and behavioral comorbidities. METHODS: Transplantation of progenitor cells from embryonic medial or caudal ganglionic eminence (MGE, CGE) were made in a well-characterized mouse model of status epilepticus-induced epilepsy (systemic pilocarpine). Behavioral testing (handling and open field), continuous video-electroencephalographic (vEEG) monitoring, and slice electrophysiology outcomes were obtained up to 270 days after transplantation (DAT). Post-hoc immunohistochemistry was used to confirm cell identity. RESULTS: MGE progenitors transplanted into the hippocampus of epileptic mice rescued handling and open field deficits starting at 60 DAT. In these same mice, an 84% to 88% reduction in seizure activity was observed between 180 and 210 DAT. Inhibitory postsynaptic current frequency, measured on pyramidal neurons in acute hippocampal slices at 270 DAT, was reduced in epileptic mice but restored to naïve levels in epileptic mice receiving MGE transplants. No reduction in seizure activity was observed in epileptic mice receiving intrahippocampal CGE progenitors. INTERPRETATION: Our findings demonstrate that transplanted MGE progenitors enhance functional GABA-mediated inhibition, reduce spontaneous seizure frequency, and rescue behavioral deficits in a chronic epileptic animal model more than 6 months after treatment. Ann Neurol 2017;82:530-542.
[Mh] Termos MeSH primário: Epilepsia/cirurgia
Transplante de Células-Tronco/métodos
Ácido gama-Aminobutírico/metabolismo
[Mh] Termos MeSH secundário: Animais
Diferenciação Celular
Convulsivantes/toxicidade
Modelos Animais de Doenças
Embrião de Mamíferos
Epilepsia/induzido quimicamente
Comportamento Exploratório/fisiologia
Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos
Potenciais Pós-Sinápticos Inibidores/fisiologia
Interneurônios/efeitos dos fármacos
Interneurônios/fisiologia
Masculino
Eminência Mediana/citologia
Camundongos
Camundongos Transgênicos
Proteínas Nucleares/genética
Proteínas Nucleares/metabolismo
Pilocarpina/toxicidade
Hidrobrometo de Escopolamina/toxicidade
Células-Tronco/metabolismo
Fator Nuclear 1 de Tireoide
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Convulsants); 0 (Nuclear Proteins); 0 (Thyroid Nuclear Factor 1); 0 (Transcription Factors); 01MI4Q9DI3 (Pilocarpine); 451IFR0GXB (Scopolamine Hydrobromide); 56-12-2 (gamma-Aminobutyric Acid)
[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:170824
[St] Status:MEDLINE
[do] DOI:10.1002/ana.25021


  7 / 1151 MEDLINE  
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[PMID]:28677170
[Au] Autor:Matsubara D; Soda M; Yoshimoto T; Amano Y; Sakuma Y; Yamato A; Ueno T; Kojima S; Shibano T; Hosono Y; Kawazu M; Yamashita Y; Endo S; Hagiwara K; Fukayama M; Takahashi T; Mano H; Niki T
[Ad] Endereço:Division of Integrative Pathology, Jichi Medical University, Shimotsukeshi, Japan.
[Ti] Título:Inactivating mutations and hypermethylation of the NKX2-1/TTF-1 gene in non-terminal respiratory unit-type lung adenocarcinomas.
[So] Source:Cancer Sci;108(9):1888-1896, 2017 Sep.
[Is] ISSN:1349-7006
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The major driver mutations of lung cancer, EGFR mutations and EML4-ALK fusion, are mainly detected in terminal respiratory unit (TRU)-type lung adenocarcinomas, which typically show lepidic and/or papillary patterns, but are rarely associated with a solid or invasive mucinous morphology. In order to elucidate the key genetic events in non-TRU-type lung cancer, we carried out whole-exome sequencing on 43 non-TRU-type lung adenocarcinomas based on morphology (17 acinar, nine solid, and two enteric adenocarcinomas, and 15 adenocarcinomas with a mucinous morphology). Our analysis identified mutations in TP53 (16/43, 37.2%), KRAS (13/43, 30.2%), and NKX2-1/TTF-1 (7/43; 16.3%) as the top three significantly mutated genes, while the EGFR mutation was rare (1/43, 2.3%) in this cohort. Eight NKX2-1/TTF-1 mutations (five frameshift, two nonsense, and one missense) were identified, with one case harboring two distinct NKX2-1/TTF-1 mutations (one missense and one frameshift). Functional assays with the NK2 homeobox 1 (NKX2-1)/thyroid transcription factor 1 (TTF-1) mutants revealed that none of them retain the activity as a transcriptional factor. Histologically, invasive mucinous adenocarcinomas accounted for most of the NKX2-1/TTF-1 mutations (five cases), as well as one enteric and one acinar adenocarcinoma. Immunohistochemistry showed that the cohort was largely divided into TTF-1-postive/hepatocyte nuclear factor 4-α (HNF4-α)-negative and TTF-1-negative/HNF4-α-positive groups. NKX2-1/TTF-1 mutations were exclusively found in the latter, in which the gastrointestinal markers, mucin 5AC and cytokeratin 20, were frequently expressed. Bisulfite sequencing revealed that the NKX2-1/TTF-1 gene body was highly methylated in NKX2-1/TTF-1-negative cases, including those without the NKX2-1/TTF-1 mutations. The genetic or epigenetic inactivation of NKX2-1/TTF-1 may play an essential role in the development and aberrant differentiation of non-TRU-type lung adenocarcinomas.
[Mh] Termos MeSH primário: Adenocarcinoma/genética
Proteínas de Ligação a DNA/genética
Neoplasias Pulmonares/genética
Proteínas Nucleares/genética
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Adenocarcinoma/patologia
Linhagem Celular Tumoral
Metilação de DNA
Análise Mutacional de DNA
Epigênese Genética
Regulação Neoplásica da Expressão Gênica
Estudos de Associação Genética
Predisposição Genética para Doença
Células HEK293
Seres Humanos
Neoplasias Pulmonares/patologia
Mutação
Fator Nuclear 1 de Tireoide
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA-Binding Proteins); 0 (NKX2-1 protein, human); 0 (Nuclear Proteins); 0 (TTF1 protein, human); 0 (Thyroid Nuclear Factor 1); 0 (Transcription Factors)
[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:170706
[St] Status:MEDLINE
[do] DOI:10.1111/cas.13313


  8 / 1151 MEDLINE  
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[PMID]:28605545
[Au] Autor:Han B; Mohamed Z; Estebanez MS; Craigie RJ; Newbould M; Cheesman E; Padidela R; Skae M; Johnson M; Flanagan S; Ellard S; Cosgrove KE; Banerjee I; Dunne MJ
[Ad] Endereço:Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M13 9PT, United Kingdom.
[Ti] Título:Atypical Forms of Congenital Hyperinsulinism in Infancy Are Associated With Mosaic Patterns of Immature Islet Cells.
[So] Source:J Clin Endocrinol Metab;102(9):3261-3267, 2017 Sep 01.
[Is] ISSN:1945-7197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Objectives: We aimed to characterize mosaic populations of pancreatic islet cells from patients with atypical congenital hyperinsulinism in infancy (CHI-A) and the expression profile of NKX2.2, a key transcription factor expressed in ß-cells but suppressed in δ-cells in the mature pancreas. Patients/Methods: Tissue was isolated from three patients with CHI-A following subtotal pancreatectomy. CHI-A was diagnosed on the basis of islet mosaicism and the absence of histopathological hallmarks of focal and diffuse CHI (CHI-D). Immunohistochemistry was used to identify and quantify the proportions of insulin-secreting ß-cells and somatostatin-secreting δ-cells in atypical islets, and results were compared with CHI-D (n = 3) and age-matched control tissues (n = 3). Results: In CHI-A tissue, islets had a heterogeneous profile. In resting/quiescent islets, identified by a condensed cytoplasm and nuclear crowding, ß-cells were reduced to <50% of the total cell numbers in n = 65/70 islets, whereas δ-cell numbers were increased with 85% of islets (n = 49/57) containing >20% δ-cells. In comparison, all islets in control tissue (n = 72) and 99% of CHI-D islets (n = 72) were composed of >50% ß-cells, and >20% δ-cells were found only in 12% of CHI-D (n = 8/66) and 5% of control islets (n = 3/60). Active islets in CHI-A tissue contained proportions of ß-cells and δ-cells similar to those of control and CHI-D islets. Finally, when compared with active islets, quiescent islets had a twofold higher prevalence of somatostatin/NKX2.2+ coexpressed cells. Conclusions: Marked increases in NKX2.2 expression combined with increased numbers of δ-cells strongly imply that an immature δ-cell profile contributed to the pathobiology of CHI-A.
[Mh] Termos MeSH primário: Hiperinsulinismo Congênito/genética
Hiperinsulinismo Congênito/patologia
Predisposição Genética para Doença
Ilhotas Pancreáticas/patologia
Proteínas Nucleares/genética
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Biópsia por Agulha
Pré-Escolar
Estudos de Coortes
Hiperinsulinismo Congênito/cirurgia
Feminino
Seres Humanos
Imuno-Histoquímica
Lactente
Ilhotas Pancreáticas/secreção
Masculino
Mosaicismo
Pancreatectomia/métodos
Prognóstico
Valores de Referência
Índice de Gravidade de Doença
Fator Nuclear 1 de Tireoide
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Nuclear Proteins); 0 (Thyroid Nuclear Factor 1); 0 (Transcription Factors)
[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:170613
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2017-00158


  9 / 1151 MEDLINE  
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[PMID]:28546511
[Au] Autor:Herriges MJ; Tischfield DJ; Cui Z; Morley MP; Han Y; Babu A; Li S; Lu M; Cendan I; Garcia BA; Anderson SA; Morrisey EE
[Ad] Endereço:Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
[Ti] Título:The NANCI-Nkx2.1 gene duplex buffers Nkx2.1 expression to maintain lung development and homeostasis.
[So] Source:Genes Dev;31(9):889-903, 2017 May 01.
[Is] ISSN:1549-5477
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A subset of long noncoding RNAs (lncRNAs) is spatially correlated with transcription factors (TFs) across the genome, but how these lncRNA-TF gene duplexes regulate tissue development and homeostasis is unclear. We identified a feedback loop within the NANCI (Nkx2.1-associated noncoding intergenic RNA)-Nkx2.1 gene duplex that is essential for buffering Nkx2.1 expression, lung epithelial cell identity, and tissue homeostasis. Within this locus, Nkx2.1 directly inhibits NANCI, while NANCI acts in to promote Nkx2.1 transcription. Although loss of NANCI alone does not adversely affect lung development, concurrent heterozygous mutations in both NANCI and Nkx2.1 leads to persistent Nkx2.1 deficiency and reprogramming of lung epithelial cells to a posterior endoderm fate. This disruption in the NANCI-Nkx2.1 gene duplex results in a defective perinatal innate immune response, tissue damage, and progressive degeneration of the adult lung. These data point to a mechanism in which lncRNAs act as rheostats within lncRNA-TF gene duplex loci that buffer TF expression, thereby maintaining tissue-specific cellular identity during development and postnatal homeostasis.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica no Desenvolvimento
Homeostase
Pulmão/crescimento & desenvolvimento
Pulmão/fisiologia
Proteínas Nucleares/metabolismo
RNA Longo não Codificante/metabolismo
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Animais
Células Epiteliais/imunologia
Células Epiteliais/metabolismo
Seres Humanos
Imunidade Celular
Pulmão/imunologia
Camundongos
Proteínas Nucleares/genética
RNA Longo não Codificante/genética
Fator Nuclear 1 de Tireoide
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Nkx2-1 protein, mouse); 0 (Nuclear Proteins); 0 (RNA, Long Noncoding); 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:170527
[St] Status:MEDLINE
[do] DOI:10.1101/gad.298018.117


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[PMID]:28527968
[Au] Autor:Konno H; Saito H; Nanjo H; Hiroshima Y; Kurihara N; Fujishima S; Atari M; Sato Y; Motoyama S; Nakamura R; Akagami Y; Minamiya Y
[Ad] Endereço:Department of Thoracic Surgery, Akita University Graduate School of Medicine, Akita, Japan. Electronic address: konno-h@gipc.akita-u.ac.jp.
[Ti] Título:Rapid Immunohistochemistry With Thyroid Transcription Factor-1 for Pulmonary Adenocarcinoma.
[So] Source:Ann Thorac Surg;104(2):471-476, 2017 Aug.
[Is] ISSN:1552-6259
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Intraoperative pathologic diagnosis of solitary pulmonary tumors to differentiate between metastatic and primary lung cancer is extremely important to determine the appropriate range of excision. Accurate intraoperative pathologic evaluation may be often difficult, however, and needs additional immunohistochemical (IHC) evaluation to support the diagnosis. Although conventional IHC is a powerful tool for diagnosis, its clinical use is limited intraoperatively because of time constraints. To address this issue, we developed a device that enables complete and rapid IHC (R-IHC) analyses within 20 minutes. We aimed to evaluate the discriminative ability of the R-IHC with anti-thyroid transcription factor-1 (TTF-1) antibody, which is a highly specific IHC marker for primary lung adenocarcinoma. METHODS: A total of 61 pulmonary tumors that were resected at our institute from May 2011 to September 2013 were retrospectively examined. The samples were sectioned, labeled with anti-TTF-1 antibody using the R-IHC method, and pathologically evaluated. The standard used for evaluation was conventional IHC with TTF-1. RESULTS: With the R-IHC procedure, analyses were completed within 20 minutes, with a diagnostic accuracy of 96.7% (59 of 61). Among the 47 primary lung adenocarcinomas, the R-IHC detected 31 (66%) tumors that were positive for TTF-1, with a positive predictive value of 100% (31 of 31). CONCLUSIONS: Our newly developed method of R-IHC with anti-TTF-1 antibody was useful for diagnosing and differentiation of solitary pulmonary tumors. This technology may prove to be an important supplement to standard intraoperative pathologic diagnosis in routine practice.
[Mh] Termos MeSH primário: Adenocarcinoma/diagnóstico
Imuno-Histoquímica/métodos
Neoplasias Pulmonares/diagnóstico
Pulmão/metabolismo
Proteínas Nucleares/metabolismo
Fatores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Adenocarcinoma/metabolismo
Adenocarcinoma/cirurgia
Biomarcadores Tumorais/metabolismo
Diagnóstico Diferencial
Seres Humanos
Pulmão/patologia
Neoplasias Pulmonares/metabolismo
Neoplasias Pulmonares/cirurgia
Pneumonectomia
Valor Preditivo dos Testes
Reprodutibilidade dos Testes
Estudos Retrospectivos
Cirurgia Torácica Vídeoassistida
Fator Nuclear 1 de Tireoide
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (NKX2-1 protein, human); 0 (Nuclear Proteins); 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:AIM; IM
[Da] Data de entrada para processamento:170522
[St] Status:MEDLINE



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