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[PMID]:27775692
[Au] Autor:Aeffner F; Martin NT; Peljto M; Black JC; Major JK; Jangani M; Ports MO; Krueger JS; Young GD
[Ad] Endereço:Flagship Biosciences Inc., Westminster, CO, USA.
[Ti] Título:Quantitative assessment of pancreatic cancer precursor lesions in IHC-stained tissue with a tissue image analysis platform.
[So] Source:Lab Invest;96(12):1327-1336, 2016 12.
[Is] ISSN:1530-0307
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Tissue image analysis (tIA) is emerging as a powerful tool for quantifying biomarker expression and distribution in complex diseases and tissues. Pancreatic ductal adenocarcinoma (PDAC) develops in a highly complex and heterogeneous tissue environment and, generally, has a very poor prognosis. Early detection of PDAC is confounded by limited knowledge of the pre-neoplastic disease stages and limited methods to quantitatively assess disease heterogeneity. We sought to develop a tIA approach to assess the most common PDAC precursor lesions, pancreatic intraepithelial neoplasia (PanIN), in tissues from Kras ; Trp53 ; Pdx-Cre (KPC) mice, a validated model of PDAC development. tIA profiling of training regions of PanIN and tumor microenvironment (TME) cells was utilized to guide identification of PanIN/TME tissue compartment stratification criteria. A custom CellMap algorithm implementing these criteria was applied to whole-slide images of KPC mice pancreata sections to quantify p53 and Ki-67 biomarker staining in each tissue compartment as a proof-of-concept for the algorithm platform. The algorithm robustly identified a higher percentage of p53-positive cells in PanIN lesions relative to the TME, whereas no difference was observed for Ki-67. Ki-67 expression was also quantified in a human pancreatic tissue sample available to demonstrate the translatability of the CellMap algorithm to human samples. Together, our data demonstrated the utility of CellMap to enable objective and quantitative assessments, across entire tissue sections, of PDAC precursor lesions in preclinical and clinical models of this disease to support efforts leading to novel insights into disease progression, diagnostic markers, and potential therapeutic targets.
[Mh] Termos MeSH primário: Adenocarcinoma in Situ/diagnóstico
Carcinoma Ductal Pancreático/diagnóstico
Pâncreas/patologia
Neoplasias Pancreáticas/diagnóstico
Lesões Pré-Cancerosas/diagnóstico
Proteína Supressora de Tumor p53/metabolismo
[Mh] Termos MeSH secundário: Adenocarcinoma in Situ/diagnóstico por imagem
Adenocarcinoma in Situ/metabolismo
Adenocarcinoma in Situ/patologia
Algoritmos
Animais
Automação Laboratorial
Carcinoma Ductal Pancreático/diagnóstico por imagem
Carcinoma Ductal Pancreático/metabolismo
Carcinoma Ductal Pancreático/patologia
Cruzamentos Genéticos
Modelos Animais de Doenças
Detecção Precoce de Câncer/métodos
Seres Humanos
Processamento de Imagem Assistida por Computador
Imuno-Histoquímica
Antígeno Ki-67/metabolismo
Camundongos Mutantes
Camundongos Transgênicos
Pâncreas/metabolismo
Neoplasias Pancreáticas/diagnóstico por imagem
Neoplasias Pancreáticas/metabolismo
Neoplasias Pancreáticas/patologia
Lesões Pré-Cancerosas/diagnóstico por imagem
Lesões Pré-Cancerosas/metabolismo
Lesões Pré-Cancerosas/patologia
Software
Organismos Livres de Patógenos Específicos
Bancos de Tecidos
Ultrassonografia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ki-67 Antigen); 0 (Tumor Suppressor Protein p53)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1038/labinvest.2016.111


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[PMID]:28842505
[Au] Autor:Allam H; Johnson BP; Zhang M; Lu Z; Cannon MJ; Abbott KL
[Ad] Endereço:From the Medical Microbiology and Immunology Department, Menofiya University, Cairo 11795, Egypt.
[Ti] Título:The glycosyltransferase GnT-III activates Notch signaling and drives stem cell expansion to promote the growth and invasion of ovarian cancer.
[So] Source:J Biol Chem;292(39):16351-16359, 2017 Sep 29.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glycosylation changes associated with cellular transformation can facilitate the growth and progression of tumors. Previously we discovered that the gene encoding the glycosyltransferase GnT-III is elevated in epithelial ovarian carcinomas (EOCs) and leads to the production of abnormal truncated -linked glycan structures instead of the typical bisected forms. In this study, we are interested in discovering how these abnormal glycans impact the growth and progression of ovarian cancer. We have discovered using stable shRNA gene suppression that GnT-III expression controls the expansion of side-population cells, also known as cancer stem cells. More specifically, we found that GnT-III expression regulates the levels and activation of the heavily glycosylated Notch receptor involved in normal and malignant development. Suppression of GnT-III in EOC cell lines and primary tumor-derived cells resulted in an inhibition of Notch signaling that was more potent than pharmacologic blockage of Notch activation via γ-secretase inhibition. The inhibition resulted from the redirection of the Notch receptor to the lysosome, a novel mechanism. These findings demonstrate a new role for bisecting glycosylation in the control of Notch transport and demonstrate the therapeutic potential of inhibiting GnT-III as a treatment for controlling EOC growth and recurrence.
[Mh] Termos MeSH primário: Carcinoma/metabolismo
N-Acetilglucosaminiltransferases/metabolismo
Proteínas de Neoplasias/metabolismo
Células-Tronco Neoplásicas/metabolismo
Neoplasias Ovarianas/metabolismo
Receptores Notch/agonistas
Transdução de Sinais
[Mh] Termos MeSH secundário: Animais
Carcinoma/patologia
Carcinoma/terapia
Linhagem Celular Tumoral
Feminino
Glicosilação
Seres Humanos
Estimativa de Kaplan-Meier
Camundongos Endogâmicos NOD
N-Acetilglucosaminiltransferases/antagonistas & inibidores
N-Acetilglucosaminiltransferases/genética
Invasividade Neoplásica
Proteínas de Neoplasias/antagonistas & inibidores
Proteínas de Neoplasias/genética
Células-Tronco Neoplásicas/patologia
Neoplasias Ovarianas/patologia
Neoplasias Ovarianas/terapia
Ovário/metabolismo
Ovário/patologia
Processamento de Proteína Pós-Traducional
Interferência de RNA
Terapêutica com RNAi
Receptores Notch/metabolismo
Bancos de Tecidos
Carga Tumoral
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Neoplasm Proteins); 0 (Receptors, Notch); EC 2.4.1.- (N-Acetylglucosaminyltransferases); EC 2.4.1.144 (beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170827
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.783936


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[PMID]:28760828
[Au] Autor:Carlomagno Y; Chung DC; Yue M; Castanedes-Casey M; Madden BJ; Dunmore J; Tong J; DeTure M; Dickson DW; Petrucelli L; Cook C
[Ad] Endereço:From the Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224.
[Ti] Título:An acetylation-phosphorylation switch that regulates tau aggregation propensity and function.
[So] Source:J Biol Chem;292(37):15277-15286, 2017 Sep 15.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The aberrant accumulation of tau protein is a pathological hallmark of a class of neurodegenerative diseases known as tauopathies, including Alzheimer's disease and related dementias. On the basis of previous observations that tau is a direct substrate of histone deacetylase 6 (HDAC6), we sought to map all HDAC6-responsive sites in tau and determine how acetylation in a site-specific manner affects tau's biophysical properties Our findings indicate that several acetylation sites in tau are responsive to HDAC6 and that acetylation on Lys-321 (within a KCGS motif) is both essential for acetylation-mediated inhibition of tau aggregation and a molecular tactic for preventing phosphorylation on the downstream Ser-324 residue. To determine the functional consequence of this HDAC6-regulated phosphorylation event, we examined tau's ability to promote microtubule assembly and found that phosphorylation of Ser-324 interferes with the normal microtubule-stabilizing function of tau. Tau phosphorylation of Ser-324 (pSer-324) has not previously been evaluated in the context of tauopathy, and here we observed increased deposition of pSer-324-positive tau both in mouse models of tauopathy and in patients with Alzheimer's disease. These findings uncover a novel acetylation-phosphorylation switch at Lys-321/Ser-324 that coordinately regulates tau polymerization and function. Because the disease relevance of this finding is evident, additional studies are needed to examine the role of pSer-324 in tau pathobiology and to determine whether therapeutically modulating this acetylation-phosphorylation switch affects disease progression .
[Mh] Termos MeSH primário: Doença de Alzheimer/metabolismo
Histona Desacetilases/metabolismo
Neurônios/metabolismo
Processamento de Proteína Pós-Traducional
Tauopatias/metabolismo
Proteínas tau/metabolismo
[Mh] Termos MeSH secundário: Acetilação/efeitos dos fármacos
Idoso
Doença de Alzheimer/tratamento farmacológico
Doença de Alzheimer/patologia
Substituição de Aminoácidos
Animais
Animais Recém-Nascidos
Células Cultivadas
Córtex Cerebral/citologia
Córtex Cerebral/efeitos dos fármacos
Córtex Cerebral/metabolismo
Córtex Cerebral/patologia
Feminino
Desacetilase 6 de Histona
Inibidores de Histona Desacetilases/farmacologia
Histona Desacetilases/química
Seres Humanos
Lisina/metabolismo
Masculino
Camundongos Transgênicos
Mutação
Neurônios/citologia
Neurônios/efeitos dos fármacos
Neurônios/patologia
Fosforilação/efeitos dos fármacos
Processamento de Proteína Pós-Traducional/efeitos dos fármacos
Serina/metabolismo
Tauopatias/tratamento farmacológico
Tauopatias/patologia
Bancos de Tecidos
Proteínas tau/química
Proteínas tau/genética
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Histone Deacetylase Inhibitors); 0 (tau Proteins); 452VLY9402 (Serine); EC 3.5.1.98 (HDAC6 protein, human); EC 3.5.1.98 (Hdac6 protein, mouse); EC 3.5.1.98 (Histone Deacetylase 6); EC 3.5.1.98 (Histone Deacetylases); K3Z4F929H6 (Lysine)
[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:10.1074/jbc.M117.794602


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[PMID]:28732082
[Au] Autor:Glover J; Man TK; Barkauskas DA; Hall D; Tello T; Sullivan MB; Gorlick R; Janeway K; Grier H; Lau C; Toretsky JA; Borinstein SC; Khanna C; Fan TM; COG Osteosarcoma Biology Group
[Ad] Endereço:Children's Cancer and Blood Disorders Program, Randall Children's Hospital, Portland, Oregon, United States of America.
[Ti] Título:Osteosarcoma enters a post genomic era with in silico opportunities: Generation of the High Dimensional Database for facilitating sarcoma biology research: A report from the Children's Oncology Group and the QuadW Foundation.
[So] Source:PLoS One;12(7):e0181204, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The prospective banking of osteosarcoma tissue samples to promote research endeavors has been realized through the establishment of a nationally centralized biospecimen repository, the Children's Oncology Group (COG) biospecimen bank located at the Biopathology Center (BPC)/Nationwide Children's Hospital in Columbus, Ohio. Although the physical inventory of osteosarcoma biospecimens is substantive (>15,000 sample specimens), the nature of these resources remains exhaustible. Despite judicious allocation of these high-value biospecimens for conducting sarcoma-related research, a deeper understanding of osteosarcoma biology, in particular metastases, remains unrealized. In addition the identification and development of novel diagnostics and effective therapeutics remain elusive. The QuadW-COG Childhood Sarcoma Biostatistics and Annotation Office (CSBAO) has developed the High Dimensional Data (HDD) platform to complement the existing physical inventory and to promote in silico hypothesis testing in sarcoma biology. The HDD is a relational biologic database derived from matched osteosarcoma biospecimens in which diverse experimental readouts have been generated and digitally deposited. As proof-of-concept, we demonstrate that the HDD platform can be utilized to address previously unrealized biologic questions though the systematic juxtaposition of diverse datasets derived from shared biospecimens. The continued population of the HDD platform with high-value, high-throughput and mineable datasets allows a shared and reusable resource for researchers, both experimentalists and bioinformatics investigators, to propose and answer questions in silico that advance our understanding of osteosarcoma biology.
[Mh] Termos MeSH primário: Pesquisa Biomédica
Neoplasias Ósseas
Simulação por Computador
Bases de Dados Factuais
Osteossarcoma
Bancos de Tecidos
[Mh] Termos MeSH secundário: Neoplasias Ósseas/metabolismo
Biologia Computacional
RNA Helicases DEAD-box/metabolismo
Seres Humanos
Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue
Proteínas de Membrana/metabolismo
Análise em Microsséries
Antígenos de Histocompatibilidade Menor/metabolismo
Modelos Biológicos
Osteossarcoma/metabolismo
RNA/metabolismo
Ubiquitina Tiolesterase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (C4orf34 protein, human); 0 (IGFBP-2 protein, human); 0 (Insulin-Like Growth Factor Binding Protein 2); 0 (Membrane Proteins); 0 (Minor Histocompatibility Antigens); 63231-63-0 (RNA); EC 3.1.2.15 (USP9Y protein, human); EC 3.4.19.12 (Ubiquitin Thiolesterase); EC 3.6.1.- (DDX3Y protein, human); EC 3.6.4.13 (DEAD-box RNA Helicases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181204


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[PMID]:28664917
[Au] Autor:Adishesh M; Fyson A; DeCruze SB; Kirwan J; Werner HMJ; Hapangama DK; ENITEC Consortium
[Ad] Endereço:Liverpool Women's Hospital NHS Foundation Trust, Crown Street, Liverpool L8 7SS, UK.
[Ti] Título:Harmonisation of biobanking standards in endometrial cancer research.
[So] Source:Br J Cancer;117(4):485-493, 2017 Aug 08.
[Is] ISSN:1532-1827
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Endometrial cancer is the most common gynaecological cancer and its incidence is predicted to escalate by 50-100% in 2025 with a parallel increase in associated mortality. Variations in the collection, processing and storage of biospecimens can affect the generalisability of the scientific data. We aimed to harmonise the collection of biospecimens, clinical data relevant to endometrial cancer and to develop standard operative procedures for the collection, processing and storage of endometrial cancer biospecimens. METHODS: We designed research tools, which were evaluated and revised through three consensus rounds - to obtain local/regional, national and European consensus. Modified final tools were disseminated to a panel (n=40) representing all stakeholders in endometrial cancer research for consensus generation. RESULTS: The final consensus demonstrated unanimous agreement with the minimal surgical and patient data collection tools. A high level of agreement was also observed for the other remaining standard tools. CONCLUSIONS: We here present the final versions of the tools, which are freely available and easily accessible to all endometrial cancer researchers. We believe that these tools will facilitate rapid progress in endometrial cancer research, both in future collaborations and in large-scale multicentre studies.
[Mh] Termos MeSH primário: Pesquisa Biomédica
Neoplasias do Endométrio/cirurgia
Manejo de Espécimes/normas
Bancos de Tecidos/normas
[Mh] Termos MeSH secundário: Consenso
Neoplasias do Endométrio/patologia
Feminino
Guias como Assunto
Seres Humanos
Inquéritos e Questionários
[Pt] Tipo de publicação:CONSENSUS DEVELOPMENT CONFERENCE; JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170701
[St] Status:MEDLINE
[do] DOI:10.1038/bjc.2017.194


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[PMID]:28442345
[Au] Autor:Wetzel HN; Webster RP; Saeed FO; Kirley TL; Ball WJ; Norman AB
[Ad] Endereço:Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0575, USA.
[Ti] Título:Characterization of a recombinant humanized anti-cocaine monoclonal antibody produced from multiple clones for the selection of a master cell bank candidate.
[So] Source:Biochem Biophys Res Commun;487(3):690-694, 2017 Jun 03.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We have generated a humanized anti-cocaine monoclonal antibody (mAb), which is at an advanced stage of pre-clinical development. We report here in vitro binding affinity studies, and in vivo pharmacokinetic and efficacy studies of the recombinant mAb. The overall aim was to characterize the recombinant antibody from each of the three highest producing transfected clones and to select one to establish a master cell bank. In mAb pharmacokinetic studies, after injection with h2E2 (120 mg/kg iv) blood was collected from the tail tip of mice over 28 days. Antibody concentrations were quantified using ELISA. The h2E2 concentration as a function of time was fit using a two-compartment pharmacokinetic model. To test in vivo efficacy, mice were injected with h2E2 (120 mg/kg iv), then one hour later injected with an equimolar dose of cocaine. Blood and brain were collected 5 min after cocaine administration. Cocaine concentrations were quantified using LC/MS. The affinity of the antibody for cocaine was determined using a [ H] cocaine binding assay. All three antibodies had long elimination half-lives, 2-5 nM Kd for cocaine, and prevented cocaine's entry into the brain by sequestering it in the plasma. Pharmacokinetic and radioligand binding assays supported designation of the highest producing clone 85 as the master cell bank candidate. Overall, the recombinant h2E2 showed favorable binding properties, pharmacokinetics, and in vivo efficacy.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/química
Anticorpos Monoclonais/imunologia
Encéfalo/imunologia
Cocaína/química
Cocaína/imunologia
Bancos de Tecidos
[Mh] Termos MeSH secundário: Anticorpos Monoclonais/genética
Clonagem Molecular/métodos
Desenho de Drogas
Taxa de Depuração Metabólica
Ligação Proteica
Engenharia de Proteínas/métodos
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/imunologia
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Recombinant Proteins); I5Y540LHVR (Cocaine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170819
[Lr] Data última revisão:
170819
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170427
[St] Status:MEDLINE


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[PMID]:28389615
[Au] Autor:Lee SJ; Jee YH; Jung KJ; Hong S; Shin ES; Jee SH
[Ad] Endereço:From the Department of Public Health, Graduate School (S.J.L.), Institute for Health Promotion (K.J.J., S.H., S.H.J.), and Department of Epidemiology (S.H.J.), Yonsei University, Seoul, Republic of Korea; MRC Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Un
[Ti] Título:Bilirubin and Stroke Risk Using a Mendelian Randomization Design.
[So] Source:Stroke;48(5):1154-1160, 2017 May.
[Is] ISSN:1524-4628
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND PURPOSE: Circulating bilirubin, a natural antioxidant, is associated with decreased risk of stroke. However, the nature of the relationship between the two remains unknown. We used a Mendelian randomization analysis to assess the causal effect of serum bilirubin on stroke risk in Koreans. METHODS: The 14 single-nucleotide polymorphisms (SNPs) (<10 ) including rs6742078 of uridine diphosphoglucuronyl-transferase were selected from genome-wide association study of bilirubin level in the KCPS-II (Korean Cancer Prevention Study-II) Biobank subcohort consisting of 4793 healthy Korean and 806 stroke cases. Weighted genetic risk score was calculated using 14 SNPs selected from the top SNPs. RESULTS: Both rs6742078 (F statistics=138) and weighted genetic risk score with 14 SNPs (F statistics=187) were strongly associated with bilirubin levels. Simultaneously, serum bilirubin level was associated with decreased risk of stroke in an ordinary least-squares analysis. However, in 2-stage least-squares Mendelian randomization analysis, no causal relationship between serum bilirubin and stroke risk was found. CONCLUSIONS: There is no evidence that bilirubin level is causally associated with risk of stroke in Koreans. Therefore, bilirubin level is not a risk determinant of stroke.
[Mh] Termos MeSH primário: Bilirrubina/sangue
Glucuronosiltransferase/genética
Acidente Vascular Cerebral/sangue
Bancos de Tecidos
[Mh] Termos MeSH secundário: Adulto
Idoso
Bilirrubina/genética
Estudos de Coortes
Feminino
Estudo de Associação Genômica Ampla
Seres Humanos
Masculino
Meia-Idade
Polimorfismo de Nucleotídeo Único
República da Coreia
Risco
Acidente Vascular Cerebral/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.4.1.- (UGT1A1 enzyme); EC 2.4.1.17 (Glucuronosyltransferase); RFM9X3LJ49 (Bilirubin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170630
[Lr] Data última revisão:
170630
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170409
[St] Status:MEDLINE
[do] DOI:10.1161/STROKEAHA.116.015083


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[PMID]:28364523
[Au] Autor:Kokai LE; Traktuev DO; Zhang L; Merfeld-Clauss S; DiBernardo G; Lu H; Marra KG; Donnenberg A; Donnenberg V; Meyer EM; Fodor PB; March KL; Rubin JP
[Ad] Endereço:Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
[Ti] Título:Adipose Stem Cell Function Maintained with Age: An Intra-Subject Study of Long-Term Cryopreserved Cells.
[So] Source:Aesthet Surg J;37(4):454-463, 2017 04 01.
[Is] ISSN:1527-330X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: The progressive decline in tissue mechanical strength that occurs with aging is hypothesized to be due to a loss of resident stem cell number and function. As such, there is concern regarding use of autologous adult stem cell therapy in older patients. To abrogate this, many patients elect to cryopreserve the adipose stromal-vascular fraction (SVF) of lipoaspirate, which contains resident adipose stem cells (ASC). However, it is not clear yet if there is any clinical benefit from banking cells at a younger age. Objectives: We performed a comparative analysis of SVF composition and ASC function from cells obtained under GMP conditions from the same three patients with time gap of 7 to 12 years. Methods: SVF, cryobanked under good manufacturing practice (GMP) conditions, was thawed and cell yield, viability, and cellular composition were assessed. In parallel, ASC proliferation and efficiency of tri-lineage differentiation were evaluated. Results: The results showed no significant differences existed in cell yield and SVF subpopulation composition within the same patient between harvest procedures 7 to 12 years apart. Further, no change in proliferation rates of cultured ASCs was found, and expanded cells from all patients were capable of tri-lineage differentiation. Conclusions: By harvesting fat from the same patient at two time points, we have shown that despite the natural human aging process, the prevalence and functional activity of ASCs in an adult mesenchymal stem cell, is highly preserved. Level of Evidence: 5.
[Mh] Termos MeSH primário: Tecido Adiposo/citologia
Células-Tronco Adultas/fisiologia
Envelhecimento/fisiologia
Senescência Celular/fisiologia
Células Mesenquimais Estromais/fisiologia
Transplante de Células-Tronco/métodos
Células Estromais/fisiologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Fatores Etários
Idoso
Idoso de 80 Anos ou mais
Diferenciação Celular
Proliferação Celular
Células Cultivadas
Criopreservação
Feminino
Citometria de Fluxo
Seres Humanos
Lipectomia
Masculino
Bancos de Tecidos/normas
Adulto Jovem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170402
[St] Status:MEDLINE
[do] DOI:10.1093/asj/sjw197


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[PMID]:28317167
[Au] Autor:Staley JR; Burgess S
[Ad] Endereço:Strangeways Research Laboratory, Department of Public Health and Primary Care, Cardiovascular Epidemiology Unit, University of Cambridge, United Kingdom.
[Ti] Título:Semiparametric methods for estimation of a nonlinear exposure-outcome relationship using instrumental variables with application to Mendelian randomization.
[So] Source:Genet Epidemiol;41(4):341-352, 2017 May.
[Is] ISSN:1098-2272
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mendelian randomization, the use of genetic variants as instrumental variables (IV), can test for and estimate the causal effect of an exposure on an outcome. Most IV methods assume that the function relating the exposure to the expected value of the outcome (the exposure-outcome relationship) is linear. However, in practice, this assumption may not hold. Indeed, often the primary question of interest is to assess the shape of this relationship. We present two novel IV methods for investigating the shape of the exposure-outcome relationship: a fractional polynomial method and a piecewise linear method. We divide the population into strata using the exposure distribution, and estimate a causal effect, referred to as a localized average causal effect (LACE), in each stratum of population. The fractional polynomial method performs metaregression on these LACE estimates. The piecewise linear method estimates a continuous piecewise linear function, the gradient of which is the LACE estimate in each stratum. Both methods were demonstrated in a simulation study to estimate the true exposure-outcome relationship well, particularly when the relationship was a fractional polynomial (for the fractional polynomial method) or was piecewise linear (for the piecewise linear method). The methods were used to investigate the shape of relationship of body mass index with systolic blood pressure and diastolic blood pressure.
[Mh] Termos MeSH primário: Análise da Randomização Mendeliana/métodos
Dinâmica não Linear
[Mh] Termos MeSH secundário: Pressão Sanguínea/genética
Índice de Massa Corporal
Simulação por Computador
Variação Genética
Seres Humanos
Modelos Genéticos
Modelos Estatísticos
Bancos de Tecidos
Reino Unido
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170321
[St] Status:MEDLINE
[do] DOI:10.1002/gepi.22041


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Texto completo SciELO Brasil
[PMID]:28300947
[Au] Autor:Longaray VK; Padoan CS; Goi PD; da Fonseca RC; Vieira DC; Oliveira FH; Kapczinski F; Magalhães PV
[Ad] Endereço:Laboratório de Psiquiatria Molecular, Hospital de Clínicas de Porto Alegre, (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
[Ti] Título:Frequency of brain tissue donation for research after suicide.
[So] Source:Rev Bras Psiquiatr;39(2):180-182, 2017 Apr-Jun.
[Is] ISSN:1809-452X
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Objectives:: To describe the frequency of brain tissue donation for research purposes by families of individuals that committed suicide. Methods:: All requests for brain tissue donation to a brain biorepository made to the families of individuals aged 18-60 years who had committed suicide between March 2014 and February 2016 were included. Cases presenting with brain damage due to acute trauma were excluded. Results:: Fifty-six cases of suicide were reported. Of these, 24 fulfilled the exclusion criteria, and 11 others were excluded because no next of kin was found to provide informed consent. Of the 21 remaining cases, brain tissue donation was authorized in nine (tissue fragments in seven and the entire organ in two). Conclusions:: Donation of brain tissue from suicide cases for research purposes is feasible. The acceptance rate of 42.8% in our sample is in accordance with international data on such donations, and similar to rates reported for neurodegenerative diseases.
[Mh] Termos MeSH primário: Pesquisa Biomédica/estatística & dados numéricos
Encéfalo
Suicídio/estatística & dados numéricos
Doadores de Tecidos/estatística & dados numéricos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Autopsia/estatística & dados numéricos
Encéfalo/anatomia & histologia
Brasil
Feminino
Seres Humanos
Consentimento Livre e Esclarecido/estatística & dados numéricos
Masculino
Meia-Idade
Doenças Neurodegenerativas/patologia
Bancos de Tecidos/estatística & dados numéricos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170317
[St] Status:MEDLINE



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