Base de dados : MEDLINE
Pesquisa : B04.265.600 [Categoria DeCS]
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[PMID]:26275802
[Au] Autor:de Castro S; Fernández-Cureses G; Andrei G; Snoeck R; Sánchez-Murcia PA; Korba B; Gago F; Balzarini J; Camarasa MJ
[Ad] Endereço:Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, E-28006 Madrid, Spain.
[Ti] Título:Conservation of antiviral activity and improved selectivity in PMEO-DAPym upon pyrimidine to triazine scaffold hopping.
[So] Source:Antiviral Res;122:64-8, 2015 Oct.
[Is] ISSN:1872-9096
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Acyclic nucleoside phosphonates incorporating 2,4-diaminotriazine (DAT) as a 5-aza-analog of the 2,4-diamino-pyrimidine (DAPym) nucleobase present in PMEO-DAPyms have been synthesized. The lead PMEO-DAT is as inhibitory against HIV, HBV, MSV and VZV replication as the parent PMEO-DAPym and equally inefficient at markedly affecting replication of HSV-1, HSV-2 and HCMV. A rationale for this similar biological profile is proposed on the basis of structural differences in the active site of the viral DNA polymerases. PMEO-DAT is, however, more selective because, unlike PMEO-DAPym, it does not stimulate secretion of ß-chemokines in cultured PBMC.
[Mh] Termos MeSH primário: Antivirais/síntese química
Antivirais/farmacologia
Herpesviridae/efeitos dos fármacos
Organofosfonatos/química
Organofosfonatos/farmacologia
Pirimidinas/química
Pirimidinas/farmacologia
Vírus do Sarcoma Murino/efeitos dos fármacos
[Mh] Termos MeSH secundário: Fármacos Anti-HIV/síntese química
Fármacos Anti-HIV/farmacologia
Células Cultivadas
Quimiocinas CC/imunologia
Quimiocinas CC/metabolismo
HIV-1/efeitos dos fármacos
Herpesvirus Humano 1/efeitos dos fármacos
Herpesvirus Humano 2/efeitos dos fármacos
Seres Humanos
Leucócitos Mononucleares/imunologia
Modelos Moleculares
Nucleosídeos
Triazinas/química
Vírus/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (6-phosphonylmethoxyethoxy-2,4-diaminopyrimidine); 0 (Anti-HIV Agents); 0 (Antiviral Agents); 0 (Chemokines, CC); 0 (Nucleosides); 0 (Organophosphonates); 0 (Pyrimidines); 0 (Triazines); K8CXK5Q32L (pyrimidine)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:150904
[Lr] Data última revisão:
150904
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150816
[St] Status:MEDLINE


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[PMID]:22465204
[Au] Autor:Facchinetti A; Biasi G
[Ti] Título:Adoptive transfer of bone marrow CD8 T lymphocytes confers full protection vs. tumor growth in M-MSV/MuLV experimental model.
[So] Source:Immunol Lett;144(1-2):78-9, 2012 May 30.
[Is] ISSN:1879-0542
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Mh] Termos MeSH primário: Linfócitos T CD8-Positivos/imunologia
Imunoterapia Adotiva/métodos
Vírus do Sarcoma Murino de Moloney/patogenicidade
Infecções por Retroviridae
Vírus do Sarcoma Murino/patogenicidade
Sarcoma Experimental/imunologia
Sarcoma Experimental/terapia
Infecções Tumorais por Vírus
[Mh] Termos MeSH secundário: Animais
Células da Medula Óssea/citologia
Células da Medula Óssea/imunologia
Camundongos
Vírus do Sarcoma Murino de Moloney/imunologia
Infecções por Retroviridae/imunologia
Infecções por Retroviridae/terapia
Infecções por Retroviridae/virologia
Vírus do Sarcoma Murino/imunologia
Sarcoma Experimental/patologia
Sarcoma Experimental/virologia
Infecções Tumorais por Vírus/imunologia
Infecções Tumorais por Vírus/terapia
Infecções Tumorais por Vírus/virologia
[Pt] Tipo de publicação:LETTER
[Em] Mês de entrada:1208
[Cu] Atualização por classe:120430
[Lr] Data última revisão:
120430
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120403
[St] Status:MEDLINE
[do] DOI:10.1016/j.imlet.2012.03.003


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[PMID]:21902856
[Au] Autor:Oarada M; Tsuzuki T; Nikawa T; Kohno S; Hirasaka K; Gonoi T
[Ad] Endereço:Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8673, Japan. motoko.o@faculty.chiba-u.jp
[Ti] Título:Refeeding with a high-protein diet after a 48 h fast causes acute hepatocellular injury in mice.
[So] Source:Br J Nutr;107(10):1435-44, 2012 May.
[Is] ISSN:1475-2662
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Elucidating the effects of refeeding a high-protein diet after fasting on disease development is of interest in relation to excessive protein ingestion and irregular eating habits in developed countries. The objective of the present study was to address the hepatic effects of refeeding a high-protein diet after fasting. Mice were fasted for 48 h and then refed with a test diet containing 3, 15, 35, 40, 45 or 50 % casein. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and liver immediate-early gene expression levels were sequentially measured for the first 24 h after initiation of refeeding. Refeeding with a 50 % casein diet after 48 h of fasting led to a rapid (within 2-3 h) and abnormal elevation in serum ALT (P = 0·006) and AST (P = 0·001) activities and a marked increase in liver Finkel-Biskis-Jinkins (FBJ) osteosarcoma oncogene (P = 0·007) and nuclear receptor subfamily 4, group A, member 1 (P = 0·002) mRNA levels. In contrast, refeeding of the 3, 15 or 35 % casein diets produced no substantial increases in serum ALT and AST activities in mice. Refeeding of 40, 45 or 50 % casein increased serum ALT and AST activities in proportion to this dietary casein content. In mice refed the 3, 15 or 35, but not 50 %, casein diets, liver heat shock protein 72 transcript levels greatly increased. We conclude from these data that the consumption of a high-protein diet after fasting causes acute hepatocellular injury in healthy animals, and propose that careful attention should be paid to the use of such diets.
[Mh] Termos MeSH primário: Dieta
Proteínas na Dieta/efeitos adversos
Jejum
Genes Precoces
Fígado/efeitos dos fármacos
Transaminases/sangue
[Mh] Termos MeSH secundário: Alanina Transaminase/sangue
Animais
Aspartato Aminotransferases/sangue
Caseínas/administração & dosagem
Caseínas/efeitos adversos
Doença Hepática Induzida por Substâncias e Drogas/etiologia
Doença Hepática Induzida por Substâncias e Drogas/metabolismo
Proteínas na Dieta/administração & dosagem
Relação Dose-Resposta a Droga
Feminino
Proteínas de Choque Térmico HSP72/genética
Proteínas de Choque Térmico HSP72/metabolismo
Fígado/enzimologia
Fígado/metabolismo
Camundongos
Camundongos Endogâmicos BALB C
RNA Mensageiro/metabolismo
Vírus do Sarcoma Murino
Transcrição Genética/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Caseins); 0 (Dietary Proteins); 0 (HSP72 Heat-Shock Proteins); 0 (RNA, Messenger); EC 2.6.1.- (Transaminases); EC 2.6.1.1 (Aspartate Aminotransferases); EC 2.6.1.2 (Alanine Transaminase)
[Em] Mês de entrada:1207
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:110910
[St] Status:MEDLINE
[do] DOI:10.1017/S0007114511004521


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[PMID]:20199087
[Au] Autor:Suijkerbuijk BM; Niculescu-Duvaz I; Gaulon C; Dijkstra HP; Niculescu-Duvaz D; Ménard D; Zambon A; Nourry A; Davies L; Manne HA; Friedlos F; Ogilvie LM; Hedley D; Lopes F; Preece NP; Moreno-Farre J; Raynaud FI; Kirk R; Whittaker S; Marais R; Springer CJ
[Ad] Endereço:The Institute of Cancer Research, Cancer Research UK Centre for Cancer Therapeutics, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom.
[Ti] Título:Development of novel, highly potent inhibitors of V-RAF murine sarcoma viral oncogene homologue B1 (BRAF): increasing cellular potency through optimization of a distal heteroaromatic group.
[So] Source:J Med Chem;53(7):2741-56, 2010 Apr 08.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We describe the design, synthesis, and optimization of a series of new inhibitors of V-RAF murine sarcoma viral oncogene homologue B1 (BRAF), a kinase whose mutant form (V600E) is implicated in several types of cancer, with a particularly high frequency in melanoma. Our previously described inhibitors with a tripartite A-B-C system (where A is a hinge binding pyrido[4,5-b]imidazolone system, B is an aryl spacer group, and C is a heteroaromatic group) were potent against purified (V600E)BRAF in vitro but were less potent in accompanying cellular assays. Substitution of different aromatic heterocycles for the phenyl based C-ring is evaluated herein as a potential means of improving the cellular potencies of these inhibitors. Substituted pyrazoles, particularly 3-tert-butyl-1-aryl-1H-pyrazoles, increase the cellular potencies without detrimental effects on the potency on isolated (V600E)BRAF. Thus, compounds have been synthesized that inhibit, with low nanomolar concentrations, (V600E)BRAF, its downstream signaling in cells [as measured by the reduction of the phosphorylation of extracellular regulated kinase (ERK)], and the proliferation of mutant BRAF-dependent cells. Concomitant benefits are good oral bioavailability and high plasma concentrations in vivo.
[Mh] Termos MeSH primário: Desenho de Drogas
Proteínas Oncogênicas v-raf/química
Inibidores de Proteínas Quinases/química
Inibidores de Proteínas Quinases/farmacologia
Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores
Vírus do Sarcoma Murino/enzimologia
Homologia de Sequência
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Feminino
Seres Humanos
Concentração Inibidora 50
Camundongos
Modelos Moleculares
Conformação Molecular
Inibidores de Proteínas Quinases/metabolismo
Inibidores de Proteínas Quinases/farmacocinética
Proteínas Proto-Oncogênicas B-raf/química
Proteínas Proto-Oncogênicas B-raf/metabolismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Protein Kinase Inhibitors); EC 2.7.11.1 (Oncogene Proteins v-raf); EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
[Em] Mês de entrada:1005
[Cu] Atualização por classe:161203
[Lr] Data última revisão:
161203
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:100305
[St] Status:MEDLINE
[do] DOI:10.1021/jm900607f


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[PMID]:20145199
[Au] Autor:Leenen PJ; Bechan GI; Melis M; den Broeder BJ; Löhler J; Egeler RM
[Ad] Endereço:Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands.
[Ti] Título:Heterogeneity in a mouse model of histiocytosis: transformation of Langerin+ dendritic cells, macrophages, and precursors.
[So] Source:J Leukoc Biol;87(5):949-58, 2010 May.
[Is] ISSN:1938-3673
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Neoplastic diseases of macrophages (M phi) and dendritic cells (DC), collectively called histiocytoses, are relatively rare. The etiology of most forms of histiocytosis is poorly understood, and the development of animal models is crucial for further research in this field. Previously, an animal model for malignant histiocytosis (MH), involving transformed histiocytic cells, has been generated by infecting mice with malignant histiocytosis sarcoma virus (MHSV). However, increased insight into the heterogeneity of M phi and DC, and the associated reappraisal of human proliferative diseases involving these cells inspired us to re-evaluate the mouse model. We analyzed spleen, bone marrow, and lymph nodes of susceptible mice at various time points after infection. From day 11 onwards, a heterogeneous population of cells, consisting of CD8 alpha(+) Langerin(+) DC, ER-MP58(+) CD11b(+) myeloid precursor cells, CD169(+) metallophilic M phi, and CD71(hi) erythroblasts, was affected by viral transformation. In different mice, these subsets expanded at different rates in different organs, causing a variable disease profile in terminal stages. Cell lines, which were generated from MHSV-transformed tumors, showed a DC-like morphology and phenotype, and appeared to be arrested in different stages of maturation. Upon injection into healthy mice, different preferential homing patterns were observed for the various cell lines, and the cells acquired distinct phenotypes depending on the organ of homing. This indicates that these transformed cells adapt to their microenvironment by switching between precursor, DC/Langerhans cell, and M phi phenotypes. Our results demonstrate that the MHSV model represents a heterogeneous neoplastic disease with characteristics of M phi/DC sarcomas.
[Mh] Termos MeSH primário: Transformação Celular Neoplásica
Células Dendríticas/patologia
Modelos Animais de Doenças
Sarcoma Histiocítico/patologia
Macrófagos/patologia
[Mh] Termos MeSH secundário: Animais
Células Dendríticas/metabolismo
Feminino
Células-Tronco Hematopoéticas
Imuno-Histoquímica
Macrófagos/metabolismo
Camundongos
Camundongos Endogâmicos BALB C
Vírus do Sarcoma Murino
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1005
[Cu] Atualização por classe:100430
[Lr] Data última revisão:
100430
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:100211
[St] Status:MEDLINE
[do] DOI:10.1189/jlb.0609432


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[PMID]:18069108
[Au] Autor:Miller TJ; Honchel R; Espandiari P; Knapton A; Zhang J; Sistare FD; Hanig JP
[Ad] Endereço:Division of Applied Pharmacology Research, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993-0002, USA. terry.miller@fda.hhs.gov
[Ti] Título:The utility of the K6/ODC transgenic mouse as an alternative short term dermal model for carcinogenicity testing of pharmaceuticals.
[So] Source:Regul Toxicol Pharmacol;50(1):87-97, 2008 Feb.
[Is] ISSN:0273-2300
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The use of transgenic rodents may overcome many limitations of traditional cancer studies. Regulatory perspectives continue to evolve as new models are developed and validated. The transgenic mouse, K6/ODC, develops epidermal tumors when exposed to genotoxic carcinogens. In this study, K6/ODC mice were evaluated for model fitness and health robustness in a 36-week study to determine oncogenic risk of residual DNA in vaccines from neoplastic cell substrates. K6/ODC and C57BL/6 mice were treated with T24-H-ras expression plasmid, carrier vector DNA, or saline topically or by subcutaneous injection. One group of K6/ODC mice received 7,12-dimethylbenz-[a]anthracene [DMBA] dermally. Only DMBA-treated mice developed papillomas by six weeks, increasing in incidence to 25 weeks. By week 11, many K6/ODC mice showed severe dehydration and dermal eczema. By week 32, (6/8) surviving K6/ODC mice showed loss of mobility and balance. Microscopic evaluation of tissues revealed dermal/sebaceous gland hyperplasia, follicular dystrophy, splenic atrophy, and amyloid deposition/neutrophilic infiltration within liver, heart, and spleen, in all K6/ODC mice. Pathology was not detected in C57BL/6 mice. Progressive adverse health, decreased survival, and failure to develop papillomas to the H-ras plasmid suggest that K6/ODC mice may be an inappropriate alternative model for detection of oncogenic DNA and pharmaceutical carcinogenicity testing.
[Mh] Termos MeSH primário: Modelos Animais de Doenças
Avaliação Pré-Clínica de Medicamentos/métodos
Queratina-6/genética
Ornitina Descarboxilase/genética
Neoplasias Cutâneas/induzido quimicamente
[Mh] Termos MeSH secundário: 9,10-Dimetil-1,2-benzantraceno/administração & dosagem
Animais
Testes de Carcinogenicidade/métodos
Carcinógenos/administração & dosagem
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
Rim/efeitos dos fármacos
Rim/patologia
Fígado/efeitos dos fármacos
Fígado/patologia
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Vírus do Sarcoma Murino/genética
Neoplasias Cutâneas/patologia
Baço/efeitos dos fármacos
Baço/patologia
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carcinogens); 0 (Keratin-6); 57-97-6 (9,10-Dimethyl-1,2-benzanthracene); EC 4.1.1.17 (Ornithine Decarboxylase)
[Em] Mês de entrada:0803
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:071211
[St] Status:MEDLINE


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[PMID]:16574062
[Au] Autor:Kim S; Lee K; Kim MD; Kang S; Joo CW; Kim JM; Kim SH; Yu SS; Kim S
[Ad] Endereço:ViroMed Co., Ltd., 1510-8 Bongcheon7-Dong, Gwanak-Gu, Seoul 151-818, Republic of Korea.
[Ti] Título:Factors affecting the performance of different long terminal repeats in the retroviral vector.
[So] Source:Biochem Biophys Res Commun;343(4):1017-22, 2006 May 19.
[Is] ISSN:0006-291X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The long terminal repeat (LTR) of retrovirus contains the nucleotide sequences that control gene expression. Although several different LTRs have been used in the context of retroviral vector, the activity of the various LTRs has not yet been systematically compared for their level of gene expression. We evaluated the effect of four different LTRs on gene expression using luciferase, stem cell factor, and enhanced green fluorescence protein as reporter genes. LTRs tested in this study were derived from Moloney murine leukemia virus, myeloproliferative sarcoma virus, murine stem cell virus, and spleen focus-forming virus. It was found that the level of gene expression is affected by not only LTRs but also the transgenes and the cell types in which gene expression occurs. Furthermore, the presence of other nucleotide sequences such as the internal ribosome entry site (IRES)-neo cassette could also significantly affect gene expression. Our results suggested that the LTR should be chosen carefully, more or less on an empirical basis.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica
Vetores Genéticos
Retroviridae/genética
Sequências Repetidas Terminais
Transgenes
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Genes Reporter
Proteínas de Fluorescência Verde/biossíntese
Proteínas de Fluorescência Verde/genética
Seres Humanos
Vírus da Leucemia Murina/genética
Luciferases/biossíntese
Luciferases/genética
Vírus da Leucemia Murina de Moloney/genética
Vírus do Sarcoma Murino/genética
Fator de Células-Tronco/biossíntese
Fator de Células-Tronco/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Stem Cell Factor); 0 (enhanced green fluorescent protein); 147336-22-9 (Green Fluorescent Proteins); EC 1.13.12.- (Luciferases)
[Em] Mês de entrada:0606
[Cu] Atualização por classe:061115
[Lr] Data última revisão:
061115
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:060401
[St] Status:MEDLINE


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[PMID]:16289982
[Au] Autor:Xia W; Bringmann P; McClary J; Jones PP; Manzana W; Zhu Y; Wang S; Liu Y; Harvey S; Madlansacay MR; McLean K; Rosser MP; MacRobbie J; Olsen CL; Cobb RR
[Ad] Endereço:Systems Biology, Berlex Biosciences, Richmond, CA, USA.
[Ti] Título:High levels of protein expression using different mammalian CMV promoters in several cell lines.
[So] Source:Protein Expr Purif;45(1):115-24, 2006 Jan.
[Is] ISSN:1046-5928
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:With the recent completion of the human genome sequencing project, scientists are faced with the daunting challenge of deciphering the function of these newly found genes quickly and efficiently. Equally as important is to produce milligram quantities of the therapeutically relevant gene products as quickly as possible. Mammalian expression systems provide many advantages to aid in this task. Mammalian cell lines have the capacity for proper post-translational modifications including proper protein folding and glycosylation. In response to the needs described above, we investigated the protein expression levels driven by the human CMV in the presence or absence of intron A, the mouse and rat CMV promoters with intron A, and the MPSV promoter in plasmid expression vectors. We evaluated the different promoters using an in-house plasmid vector backbone. The protein expression levels of four genes of interest driven by these promoters were evaluated in HEK293EBNA and CHO-K1 cells. Stable and transient transfected cells were utilized. In general, the full-length human CMV, in the presence of intron A, gave the highest levels of protein expression in transient transfections in both cell lines. However, the MPSV promoter resulted in the highest levels of stable protein expression in CHO-K1 cells. Using the CMV driven constitutive promoters in the presence of intron A, we have been able to generate >10 microg/ml of recombinant protein using transient transfections.
[Mh] Termos MeSH primário: Citomegalovirus/genética
Regulação da Expressão Gênica
Vetores Genéticos/genética
Regiões Promotoras Genéticas
[Mh] Termos MeSH secundário: Animais
Células CHO
Linhagem Celular
Cricetinae
Seres Humanos
Camundongos
RNA Mensageiro/genética
Ratos
Proteínas Recombinantes de Fusão/biossíntese
Proteínas Recombinantes de Fusão/genética
Vírus do Sarcoma Murino/genética
Transcrição Genética/genética
Transfecção
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (RNA, Messenger); 0 (Recombinant Fusion Proteins)
[Em] Mês de entrada:0604
[Cu] Atualização por classe:081121
[Lr] Data última revisão:
081121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:051118
[St] Status:MEDLINE


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[PMID]:16335231
[Au] Autor:Zarudnaya MI; Kolomiets IM; Potyahaylo AL; Hovorun DM
[Ad] Endereço:Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv. m.i.zarudna@imbg.org.ua
[Ti] Título:Dimer linkage structure in retroviruses: models that include both duplex and quadruplex domains.
[So] Source:Ukr Biokhim Zh (1999);77(2):5-15, 2005 Mar-Apr.
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:Genome of all known retroviruses consists of two identical molecules of RNA, which are non-covalently linked. The most stable contact site between two RNA molecules is located near their 5' ends. The molecular interactions in the dimer linkage structure (DLS) in mature virions are currently unknown. Recently we suggested that the dimer linkage structure in human immunodeficiency virus 1 (HIV-1) contains both duplex and quadruplex domains and proposed a model of DLS in HIV-1Mal (Central African virus). In this paper we showed that similar models can be also built for HIV- 1Lai, a representative of the North-American and European viruses. One of the double-stranded domains in the model structures represents either an extended duplex formed by different pathways (through base pair melting and subsequent reannealing or by a recombination mechanism) or kissing loop complex. The quadruplexes contain both G- and mixed tetrads, for example, G.C.G.C or A.U.A.U. Phylogenetic analysis of 350 isolates from NCBI database showed that similar models of DLS are predictable practically for all HIV-1 isolates surveyed. A model of dimer linkage structure in Moloney murine sarcoma virus (MuSV) is also presented. The structure includes a duplex formed by the palindromic sequences and several quadruplexes.
[Mh] Termos MeSH primário: Genoma Viral
RNA Viral/química
Retroviridae/genética
[Mh] Termos MeSH secundário: Animais
Dimerização
HIV-1/genética
Seres Humanos
Camundongos
Modelos Biológicos
RNA Viral/genética
Vírus do Sarcoma Murino/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (RNA, Viral)
[Em] Mês de entrada:0601
[Cu] Atualização por classe:150803
[Lr] Data última revisão:
150803
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:051213
[St] Status:MEDLINE


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[PMID]:16000062
[Au] Autor:Engels B; Noessner E; Frankenberger B; Blankenstein T; Schendel DJ; Uckert W
[Ad] Endereço:Institute of Biology, Humboldt University Berlin, 10115 Berlin, Germany.
[Ti] Título:Redirecting human T lymphocytes toward renal cell carcinoma specificity by retroviral transfer of T cell receptor genes.
[So] Source:Hum Gene Ther;16(7):799-810, 2005 Jul.
[Is] ISSN:1043-0342
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Adoptive T cell therapy of renal cell carcinoma (RCC) is limited by the difficulty in generating sufficient numbers of RCC-reactive T cells in vitro. To circumvent this problem, we cloned T cell receptor (TCR) alpha and beta chains from a tumor-infiltrating lymphocyte clone specific for an RCC tumor antigen and transferred the TCR into human T cell lines and primary T lymphocytes. Efficient TCR expression in primary T lymphocytes was obtained only with a mouse myeloproliferative sarcoma virus (MPSV)-based retroviral vector, not with a Moloney murine leukemia virus (MLV)-based vector, although both viral supernatants were similar in titer, as shown by analysis of copy number integration in transduced T cells. Reverse transcription-polymerase chain reaction analysis revealed a higher amount of TCR-encoding transcripts when T cells were transduced with the MPSV vector in comparison with the MLV vector, indicating that high TCR expression levels can be achieved by appropriate cis-regulatory vector elements. The biological activity of the transferred TCR was shown by specific lysis of RCC cells ((51)Cr release assay) and by interferon gamma and tumor necrosis factor alpha release (enzyme-linked immunosorbent assay) in an antigen-specific and HLA-A*0201-restricted fashion. Comparison of the redirected T lymphocytes with the original tumor-infiltrating lymphocyte clone revealed similar killing and cytokine secretion capabilities. The functional activity of TCR-redirected T lymphocytes was stable over time. The results demonstrate that use of an optimized retroviral vector yielded a high TCR transduction efficiency and stable and high TCR expression in primary human T lymphocytes and redirected their specificity toward RCC cells.
[Mh] Termos MeSH primário: Carcinoma de Células Renais/imunologia
Genes Codificadores dos Receptores de Linfócitos T
Neoplasias Renais/imunologia
Retroviridae/genética
Linfócitos T Citotóxicos/imunologia
[Mh] Termos MeSH secundário: Linhagem Celular
Células Cultivadas
Expressão Gênica
Vetores Genéticos
Seres Humanos
Interferon gama/metabolismo
Vírus da Leucemia Murina de Moloney/genética
Recombinação Genética
Vírus do Sarcoma Murino/genética
Transdução Genética
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Tumor Necrosis Factor-alpha); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:0512
[Cu] Atualização por classe:081121
[Lr] Data última revisão:
081121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:050708
[St] Status:MEDLINE



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