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Pesquisa : E02.095.147 [Categoria DeCS]
Referências encontradas : 4168 [refinar]
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[PMID]:29338061
[Au] Autor:Okumura N; Matsumoto D; Fukui Y; Teramoto M; Imai H; Kurosawa T; Shimada T; Kruse F; Schlötzer-Schrehardt U; Kinoshita S; Koizumi N
[Ad] Endereço:Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
[Ti] Título:Feasibility of cell-based therapy combined with descemetorhexis for treating Fuchs endothelial corneal dystrophy in rabbit model.
[So] Source:PLoS One;13(1):e0191306, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Corneal transparency is maintained by the corneal endothelium through its pump and barrier function. Severe corneal endothelial damage results in dysregulation of water flow and eventually causes corneal haziness and deterioration of visual function. In 2013, we initiated clinical research of cell-based therapy for treating corneal decompensation. In that study, we removed an 8-mm diameter section of damaged corneal endothelium without removing Descemet's membrane (the basement membrane of the corneal endothelium) and then injected cultured human corneal endothelial cells (CECs) into the anterior chamber. However, Descemet's membrane exhibits clinically abnormal structural features [i.e., multiple collagenous excrescences (guttae) and thickening] in patients with Fuchs endothelial corneal dystrophy (FECD) and the advanced cornea guttae adversely affects the quality of vision, even in patients without corneal edema. The turnover time of cornea guttae is also not certain. Therefore, we used a rabbit model to evaluate the feasibility of Descemet's membrane removal in the optical zone only, by performing a small 4-mm diameter descemetorhexis prior to CEC injection. We showed that the corneal endothelium is regenerated both on the corneal stroma (the area of Descemet's membrane removal) and on the intact peripheral Descemet's membrane, based on the expression of function-related markers and the restoration of corneal transparency. Recovery of the corneal transparency and central corneal thickness was delayed in areas of Descemet's membrane removal, but the cell density of the regenerated corneal endothelium and the thickness of the central corneal did not differ between the areas with and without residual Descemet's membrane at 14 days after CEC injection. Here, we demonstrate that removal of a pathological Descemet's membrane by a small descemetorhexis is a feasible procedure for use in combination with cell-based therapy. The current strategy might be beneficial for improving visual quality after CEC injection as a treatment for FECD.
[Mh] Termos MeSH primário: Terapia Baseada em Transplante de Células e Tecidos
Transplante de Córnea
Distrofia Endotelial de Fuchs/terapia
[Mh] Termos MeSH secundário: Idoso
Animais
Terapia Combinada
Lâmina Limitante Posterior/cirurgia
Modelos Animais de Doenças
Epitélio Posterior/patologia
Estudos de Viabilidade
Feminino
Distrofia Endotelial de Fuchs/patologia
Distrofia Endotelial de Fuchs/cirurgia
Seres Humanos
Masculino
Coelhos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191306


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[PMID]:28468247
[Au] Autor:Stephan D; Weiher H; Schmidt-Wolf IGH
[Ad] Endereço:Department of Internal Medicine III, Center for Integrated Oncology (CIO), University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany. david.stephan1701@gmail.com.
[Ti] Título:CIK Cells and HDAC Inhibitors in Multiple Myeloma.
[So] Source:Int J Mol Sci;18(5), 2017 Apr 29.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Multiple myeloma is the second most common hematological malignancy. Despite all the progress made in treating multiple myeloma, it still remains an incurable disease. Patients are left with a median survival of 4-5 years. The combined treatment of multiple myeloma with histone deacetylase inhibitors and cytokine-induced killer cells provides a promising targeted treatment option for patients. This study investigated the impact of a combined treatment compared to treatment with histone deacetylase inhibitors. The experiments revealed that a treatment with histone deacetylase (HDAC) inhibitors could reduce cell viability to 59% for KMS 18 cell line and 46% for the U-266 cell line. The combined treatment led to a decrease of cell viability to 33% for KMS 18 and 27% for the U-266 cell line, thus showing a significantly better efficacy than the single treatment.
[Mh] Termos MeSH primário: Células Matadoras Induzidas por Citocinas
Inibidores de Histona Desacetilases/uso terapêutico
Mieloma Múltiplo/terapia
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Terapia Baseada em Transplante de Células e Tecidos
Terapia Combinada/métodos
Células Matadoras Induzidas por Citocinas/transplante
Seres Humanos
Imunoterapia/métodos
Mieloma Múltiplo/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Histone Deacetylase Inhibitors)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE


  3 / 4168 MEDLINE  
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[PMID]:29298002
[Au] Autor:Voronova AD; Stepanova OV; Chadin AV; Reshetov IV; Chekhonin VP
[Ti] Título:The Cell Therapy in Traumatic Spinal Cord Injury.
[So] Source:Vestn Ross Akad Med Nauk;71(6):420-6, 2016.
[Is] ISSN:0869-6047
[Cp] País de publicação:Russia (Federation)
[La] Idioma:eng
[Ab] Resumo:The opportunities and the most promising ways of using cellular technology in traumatic spinal cord injury are considered in this review. A large number of experimental and clinical studies with the use of different types of cells: embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, Schwann cells, olfactory mucosa cells, and others ­ was conducted. The use of these types of cells in traumatic spinal cord injury treatment often demonstrated a positive therapeutic effect: the motor and sensory function recovery of the spinal cord. However, some types of cell preparations involve some methodological and ethical problems; some types of cell therapies are ineffective or give rise to side effects. These factors complicate the selection of optimal cell therapy for the traumatic spinal cord injury treatment. The most promising cells seem to be the cells of the olfactory mucosa. Getting the olfactory mucosa is considered to be a feasible and safe procedure for patients. The clinical application of the cells of the olfactory mucosa is effective in motor function recovery due to remyelination and axonal regeneration after spinal cord injury. These cells are tissue-specific and autologous since they can be obtained from a patient with spinal cord injury, and after cultivation, expansion, and directed differentiation they can be transplanted to the same patient. The presented benefits of olfactory mucosa cells open up the possibility for its clinical application in the cell therapy.
[Mh] Termos MeSH primário: Terapia Baseada em Transplante de Células e Tecidos/métodos
Traumatismos da Medula Espinal
[Mh] Termos MeSH secundário: Seres Humanos
Locomoção/fisiologia
Recuperação de Função Fisiológica
Traumatismos da Medula Espinal/fisiopatologia
Traumatismos da Medula Espinal/terapia
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE
[do] DOI:10.15690/vramn731


  4 / 4168 MEDLINE  
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[PMID]:29297623
[Au] Autor:Svistushkin VM; Starostina SV; Lyundup AV; Dedova MG; Budeikina LS; Svistushkin MV; Krasheninnikov ME; Baranovskiy DS
[Ti] Título:The Possibilities of Cell Technologies in the Treatment of Cicatricial Lesions of the Vocal Folds.
[So] Source:Vestn Ross Akad Med Nauk;71(3):190-9, 2016.
[Is] ISSN:0869-6047
[Cp] País de publicação:Russia (Federation)
[La] Idioma:eng
[Ab] Resumo:The article is a brief review of publications devoted to the problem of persistent dysphonia. The main cause of voice disorders is the scarring of the vocal folds resulting from trauma, surgical manipulation, inflammatory process. Treatment of cicatricial lesions of the vocal folds remains a challenge, as far as existing methods do not ensure the recovery of the ultrastructure of the vocal folds. The authors present modern data on the structure of the vocal folds at the cellular level. Considered pathologic processes occur in different stages of scarring. Applied technologies of phonosurgery and conservative treatment, their effectiveness and shortcomings are covered. Analysis of experimental research conducted in the world demonstrates the promise of using the methods of tissue engineering to treat scarring of the vocal folds and to restore the microstructure of the latter. Identified current issues remain unresolved, which leads to the need for further experimental and clinical studies in the treatment of this pathology.
[Mh] Termos MeSH primário: Terapia Baseada em Transplante de Células e Tecidos/métodos
Disfonia
[Mh] Termos MeSH secundário: Cicatriz/complicações
Cicatriz/diagnóstico
Disfonia/etiologia
Disfonia/terapia
Seres Humanos
Engenharia Tecidual/métodos
Disfunção da Prega Vocal/complicações
Disfunção da Prega Vocal/diagnóstico
Prega Vocal/patologia
Prega Vocal/fisiopatologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE


  5 / 4168 MEDLINE  
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[PMID]:28456379
[Au] Autor:Rivière I; Sadelain M
[Ad] Endereço:Center for Cell Engineering, Molecular Pharmacology and Immunology Programs, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
[Ti] Título:Chimeric Antigen Receptors: A Cell and Gene Therapy Perspective.
[So] Source:Mol Ther;25(5):1117-1124, 2017 May 03.
[Is] ISSN:1525-0024
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chimeric antigen receptors (CARs) are synthetic receptors that reprogram T lymphocytes to target chosen antigens. The targeting of CD19, a cell surface molecule expressed in the vast majority of leukemias and lymphomas, has been successfully translated in the clinic, earning CAR therapy a special distinction in the selection of "cancer immunotherapy" by Science as the breakthrough of the year in 2013. CD19 CAR therapy is predicated on advances in genetic engineering, T cell biology, tumor immunology, synthetic biology, target identification, cell manufacturing sciences, and regulatory compliance-the central tenets of CAR therapy. Here, we review two of these foundations: the genetic engineering approaches and cell types to engineer.
[Mh] Termos MeSH primário: Antígenos CD19/genética
Terapia Baseada em Transplante de Células e Tecidos/métodos
Leucemia/terapia
Linfoma/terapia
Proteínas Mutantes Quiméricas/genética
Receptores de Antígenos de Linfócitos T/genética
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Antígenos CD19/imunologia
Engenharia Celular/métodos
Expressão Gênica
Vetores Genéticos/química
Vetores Genéticos/imunologia
Seres Humanos
Imunoterapia/métodos
Lentivirus/genética
Lentivirus/imunologia
Leucemia/genética
Leucemia/imunologia
Leucemia/patologia
Linfoma/genética
Linfoma/imunologia
Linfoma/patologia
Proteínas Mutantes Quiméricas/imunologia
Engenharia de Proteínas/métodos
Receptores de Antígenos de Linfócitos T/imunologia
Retroviridae/genética
Retroviridae/imunologia
Linfócitos T/classificação
Linfócitos T/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antigens, CD19); 0 (CD19 molecule, human); 0 (Mutant Chimeric Proteins); 0 (Receptors, Antigen, T-Cell)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


  6 / 4168 MEDLINE  
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[PMID]:29320637
[Au] Autor:Charo RA; Sipp D
[Ad] Endereço:From the University of Wisconsin Law School, Madison (R.A.C.); and the RIKEN Center for Developmental Biology, Kobe, and Keio University School of Medicine, Keio Global Research Institute, and the RIKEN Center for Advanced Intelligence Project, Tokyo - all in Japan (D.S.).
[Ti] Título:Rejuvenating Regenerative Medicine Regulation.
[So] Source:N Engl J Med;378(6):504-505, 2018 Feb 08.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Terapia Baseada em Transplante de Células e Tecidos
Regulamentação Governamental
Medicina Regenerativa/legislação & jurisprudência
Transplante de Células-Tronco/legislação & jurisprudência
United States Food and Drug Administration
[Mh] Termos MeSH secundário: Segurança de Produtos ao Consumidor/legislação & jurisprudência
Aprovação de Drogas
Seres Humanos
Consentimento Livre e Esclarecido
Marketing de Serviços de Saúde
Governo Estadual
Transplante Autólogo/legislação & jurisprudência
Estados Unidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMp1715736


  7 / 4168 MEDLINE  
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[PMID]:29073213
[Au] Autor:Pluangnooch P; Timalsena S; Wongkajornsilp A; Soontrapa K
[Ad] Endereço:Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
[Ti] Título:Cytokine-induced killer cells: A novel treatment for allergic airway inflammation.
[So] Source:PLoS One;12(10):e0186971, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The effectiveness of cytokine-induced killer (CIK) cells for treatment of cancers has long been appreciated. Here, we report for the first time that CIK cells can be applied to treat allergic airway inflammation. Adopting from an established protocol with some modifications, we generated CIK cells ex vivo from mouse T cells, and examined their effectiveness in treatment of allergic airway inflammation using the ovalbumin-induced model of allergic airway inflammation. Based upon evaluation of bronchoalveolar lavage cellularity, T helper type2 cytokine levels and lung histology, all of which are important parameters for determining the severity of allergic airway inflammation, diseased mice treated with CIK cells showed significant reductions in all the parameters without any obvious adverse effects. Interestingly, the observed effects were comparable to those treated with dexamethasone. Thus, our study provides a novel application of CIK cells in treatment of allergic airway inflammation.
[Mh] Termos MeSH primário: Asma/imunologia
Asma/terapia
Terapia Baseada em Transplante de Células e Tecidos/métodos
Células Matadoras Induzidas por Citocinas/citologia
Hipersensibilidade/complicações
[Mh] Termos MeSH secundário: Animais
Asma/complicações
Asma/metabolismo
Citocinas/biossíntese
Eosinófilos/imunologia
Células Caliciformes/patologia
Hiperplasia
Células Matadoras Naturais/citologia
Células Matadoras Naturais/imunologia
Masculino
Camundongos
Células Th1/citologia
Células Th1/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171027
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186971


  8 / 4168 MEDLINE  
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[PMID]:28895856
[Au] Autor:Abramowski-Mock U; Delhove JM; Qasim W
[Ad] Endereço:Molecular and Cellular Immunology Unit, University college London, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
[Ti] Título:Gene Modified T Cell Therapies for Hematological Malignancies.
[So] Source:Hematol Oncol Clin North Am;31(5):913-926, 2017 Oct.
[Is] ISSN:1558-1977
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This article focuses on clinical applications of T cells transduced to express recombinant T cell receptor and chimeric antigen receptor constructs directed toward hematological malignancies, and considers newer strategies incorporating gene-editing technologies to address GvHD and host-mediated rejection. Recent data from clinical trials are reviewed, and an overview is provided of current and emerging manufacturing processes; consideration is also given to new developments in the pipeline.
[Mh] Termos MeSH primário: Terapia Baseada em Transplante de Células e Tecidos
Terapia Genética
Neoplasias Hematológicas/genética
Neoplasias Hematológicas/terapia
Linfócitos T/metabolismo
[Mh] Termos MeSH secundário: Animais
Antígenos de Neoplasias/genética
Antígenos de Neoplasias/imunologia
Biotecnologia
Terapia Baseada em Transplante de Células e Tecidos/métodos
Edição de Genes
Engenharia Genética
Terapia Genética/métodos
Vetores Genéticos/genética
Neoplasias Hematológicas/imunologia
Seres Humanos
Imunoterapia Adotiva
Receptores de Antígenos de Linfócitos T/genética
Proteínas Recombinantes de Fusão/genética
Linfócitos T/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antigens, Neoplasm); 0 (Receptors, Antigen, T-Cell); 0 (Recombinant Fusion Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170913
[St] Status:MEDLINE


  9 / 4168 MEDLINE  
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[PMID]:28860435
[Au] Autor:Ihara F; Motohashi S
[Ad] Endereço:Dept. of Medical Immunology, Graduate School of Medicine, Chiba University.
[Ti] Título:[II. Overview and Future Outlook of Immune Cell Therapy for Lung Cancer].
[So] Source:Gan To Kagaku Ryoho;44(8):650-654, 2017 Aug.
[Is] ISSN:0385-0684
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Mh] Termos MeSH primário: Terapia Baseada em Transplante de Células e Tecidos
Imunoterapia
Neoplasias Pulmonares/terapia
[Mh] Termos MeSH secundário: Animais
Antígeno B7-H1/imunologia
Seres Humanos
Neoplasias Pulmonares/imunologia
Células T Matadoras Naturais/imunologia
Recidiva
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (B7-H1 Antigen); 0 (CD274 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:170902
[St] Status:MEDLINE


  10 / 4168 MEDLINE  
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[PMID]:28854223
[Au] Autor:Yu Y; Song EM; Lee KE; Joo YH; Kim SE; Moon CM; Kim HY; Jung SA; Jo I
[Ad] Endereço:Department of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul, South Korea.
[Ti] Título:Therapeutic potential of tonsil-derived mesenchymal stem cells in dextran sulfate sodium-induced experimental murine colitis.
[So] Source:PLoS One;12(8):e0183141, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The therapeutic potential of tonsil-derived mesenchymal stem cells (TMSC) prepared from human tonsillar tissue has been studied in animal models for several diseases such as hepatic injury, hypoparathyroidism, diabetes and muscle dystrophy. In this study, we examined the therapeutic effects of TMSC in a dextran sulfate sodium (DSS)-induced colitis model. TMSC were injected in DSS-induced colitis mice via intraperitoneal injection twice (TMSC[x2]) or four times (TMSC[x4]). Control mice were injected with either phosphate-buffered saline or human embryonic kidney 293 cells. Body weight, stool condition and disease activity index (DAI) were examined daily. Colon length, histologic grading, and mRNA expression of pro-inflammatory cytokines, interleukin 1ß (IL-1ß), IL-6, IL-17 and tumor necrosis factor α, and anti-inflammatory cytokines, IL-10, IL-11 and IL-13, were also measured. Our results showed a significant improvement in survival rates and body weight gain in colitis mice injected with TMSC[x2] or TMSC[x4]. Injection with TMSC also significantly decreased DAI scores throughout the experimental period; at the end of experiment, almost complete reversal of DAI scores to normal was found in colitis mice treated with TMSC[x4]. Colon length was also significantly recovered in colitis mice treated with TMSC[x4]. However, histopathological alterations induced by DSS treatment were not apparently improved by injection with TMSC. Finally, treatment with TMSC[x4] significantly reversed the mRNA levels of IL-1ß and IL-6, although expression of all pro-inflammatory cytokines tested was induced in colitis mice. Under our experimental conditions, however, no apparent alterations in the mRNA levels of all the anti-inflammatory cytokines tested were found. In conclusion, our findings demonstrate that multiple injections with TMSC produced a therapeutic effect in a mouse model of DSS-induced colitis.
[Mh] Termos MeSH primário: Terapia Baseada em Transplante de Células e Tecidos/métodos
Colite/terapia
Transplante de Células-Tronco Mesenquimais
Células Mesenquimais Estromais/citologia
Tonsila Palatina/citologia
[Mh] Termos MeSH secundário: Animais
Peso Corporal
Criança
Colite/induzido quimicamente
Colite/imunologia
Colite/patologia
Sulfato de Dextrana
Modelos Animais de Doenças
Regulação da Expressão Gênica
Células HEK293
Seres Humanos
Injeções Intraperitoneais
Interleucina-10/genética
Interleucina-10/imunologia
Interleucina-11/genética
Interleucina-11/imunologia
Interleucina-13/genética
Interleucina-13/imunologia
Interleucina-17/genética
Interleucina-17/imunologia
Interleucina-1beta/genética
Interleucina-1beta/imunologia
Interleucina-6/genética
Interleucina-6/imunologia
Masculino
Células Mesenquimais Estromais/fisiologia
Camundongos
Camundongos Endogâmicos C57BL
Tonsila Palatina/fisiologia
Tonsila Palatina/cirurgia
Recuperação de Função Fisiológica/fisiologia
Análise de Sobrevida
Resultado do Tratamento
Fator de Necrose Tumoral alfa/genética
Fator de Necrose Tumoral alfa/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (IL10 protein, mouse); 0 (IL1B protein, mouse); 0 (Interleukin-11); 0 (Interleukin-13); 0 (Interleukin-17); 0 (Interleukin-1beta); 0 (Interleukin-6); 0 (Tumor Necrosis Factor-alpha); 0 (interleukin-6, mouse); 130068-27-8 (Interleukin-10); 9042-14-2 (Dextran Sulfate)
[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:170831
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183141



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