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Pesquisa : D03.066.707.768 [Categoria DeCS]
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[PMID]:28373352
[Au] Autor:Turner AG; Ong CY; Djoko KY; West NP; Davies MR; McEwan AG; Walker MJ
[Ad] Endereço:School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia.
[Ti] Título:The PerR-Regulated P -Type ATPase (PmtA) Acts as a Ferrous Iron Efflux Pump in Streptococcus pyogenes.
[So] Source:Infect Immun;85(6), 2017 Jun.
[Is] ISSN:1098-5522
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:(group A [GAS]) is an obligate human pathogen responsible for a broad spectrum of human disease. GAS has a requirement for metal homeostasis within the human host and, as such, tightly modulates metal uptake and efflux during infection. Metal acquisition systems are required to combat metal sequestration by the host, while metal efflux systems are essential to protect against metal overload poisoning. Here, we investigated the function of PmtA ( erR-regulated etal ransporter ), a P -type ATPase efflux pump, in invasive GAS M1T1 strain 5448. We reveal that PmtA functions as a ferrous iron [Fe(II)] efflux system. In the presence of high Fe(II) concentrations, the 5448Δ deletion mutant exhibited diminished growth and accumulated 5-fold-higher levels of intracellular Fe(II) than did the wild type and the complemented mutant. The 5448Δ deletion mutant also showed enhanced susceptibility to killing by the Fe-dependent antibiotic streptonigrin as well as increased sensitivity to hydrogen peroxide and superoxide. We suggest that the PerR-mediated control of Fe(II) efflux by PmtA is important for bacterial defense against oxidative stress. PmtA represents an exemplar for an Fe(II) efflux system in a host-adapted Gram-positive bacterial pathogen.
[Mh] Termos MeSH primário: Adenosina Trifosfatases/metabolismo
Proteínas de Bactérias/metabolismo
Ferro/metabolismo
Proteínas de Membrana Transportadoras/metabolismo
Estresse Oxidativo
Streptococcus pyogenes/enzimologia
[Mh] Termos MeSH secundário: Adenosina Trifosfatases/genética
Animais
Proteínas de Bactérias/genética
Regulação Bacteriana da Expressão Gênica
Homeostase
Seres Humanos
Peróxido de Hidrogênio/farmacologia
Proteínas de Membrana Transportadoras/genética
Camundongos
Camundongos Transgênicos
Mutação
Infecções Estreptocócicas/microbiologia
Streptococcus pyogenes/genética
Estreptonigrina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Membrane Transport Proteins); 261Q3JB310 (Streptonigrin); BBX060AN9V (Hydrogen Peroxide); E1UOL152H7 (Iron); EC 3.6.1.- (Adenosine Triphosphatases)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171123
[Lr] Data última revisão:
171123
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170405
[St] Status:MEDLINE


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[PMID]:26847951
[Au] Autor:Kong D; Zou Y; Zhang Z; Xu F; Brock NL; Zhang L; Deng Z; Lin S
[Ad] Endereço:State Key Laboratory of Microbial Metabolism, Joint International Laboratory on Metabolic &Developmental Sciences, School of Life Sciences &Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
[Ti] Título:Identification of (2S,3S)-ß-Methyltryptophan as the Real Biosynthetic Intermediate of Antitumor Agent Streptonigrin.
[So] Source:Sci Rep;6:20273, 2016 Feb 05.
[Is] ISSN:2045-2322
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Streptonigrin is a potent antitumor antibiotic, active against a wide range of mammalian tumor cells. It was reported that its biosynthesis relies on (2S,3R)-ß-methyltryptophan as an intermediate. In this study, the biosynthesis of (2S,3R)-ß-methyltryptophan and its isomer (2S,3S)-ß-methyltryptophan by enzymes from the streptonigrin biosynthetic pathway is demonstrated. StnR is a pyridoxal 5'-phosphate (PLP)-dependent aminotransferase that catalyzes a transamination between L-tryptophan and ß-methyl indolepyruvate. StnQ1 is an S-adenosylmethionine (SAM)-dependent C-methyltransferase and catalyzes ß-methylation of indolepyruvate to generate (R)-ß-methyl indolepyruvate. Although StnR exhibited a significant preference for (S)-ß-methyl indolepyruvate over the (R)-epimer, StnQ1 and StnR together catalyze (2S,3R)-ß-methyltryptophan formation from L-tryptophan. StnK3 is a cupin superfamily protein responsible for conversion of (R)-ß-methyl indolepyruvate to its (S)-epimer and enables (2S,3S)-ß-methyltryptophan biosynthesis from L-tryptophan when combined with StnQ1 and StnR. Most importantly, (2S,3S)-ß-methyltryptophan was established as the biosynthetic intermediate of the streptonigrin pathway by feeding experiments with a knockout mutant, contradicting the previous proposal that stated (2S,3R)-ß-methyltryptophan as the intermediate. These data set the stage for the complete elucidation of the streptonigrin biosynthetic pathway, which would unlock the potential of creating new streptonigrin analogues by genetic manipulation of the biosynthetic machinery.
[Mh] Termos MeSH primário: Antineoplásicos/química
Antineoplásicos/metabolismo
Estreptonigrina/metabolismo
Triptofano/análogos & derivados
[Mh] Termos MeSH secundário: Antineoplásicos/análise
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Cromatografia Líquida de Alta Pressão
Escherichia coli/metabolismo
Espectrometria de Massas
Metiltransferases/genética
Metiltransferases/metabolismo
Plasmídeos/metabolismo
S-Adenosilmetionina/análise
S-Adenosilmetionina/metabolismo
Estereoisomerismo
Streptomyces/metabolismo
Estreptonigrina/análise
Estreptonigrina/química
Triptofano/análise
Triptofano/química
Triptofano/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Bacterial Proteins); 0 (beta-methyltryptophan); 261Q3JB310 (Streptonigrin); 7LP2MPO46S (S-Adenosylmethionine); 8DUH1N11BX (Tryptophan); EC 2.1.1.- (Methyltransferases)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170111
[Lr] Data última revisão:
170111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160206
[St] Status:MEDLINE
[do] DOI:10.1038/srep20273


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[PMID]:26577188
[Au] Autor:Crepps SC; Fields EE; Galan D; Corbett JP; Von Hasseln ER; Spatafora GA
[Ad] Endereço:Department of Biology, Middlebury College, Middlebury, VT, USA.
[Ti] Título:The SloR metalloregulator is involved in the Streptococcus mutans oxidative stress response.
[So] Source:Mol Oral Microbiol;31(6):526-539, 2016 Dec.
[Is] ISSN:2041-1014
[Cp] País de publicação:Denmark
[La] Idioma:eng
[Ab] Resumo:SloR, a 25-kDa metalloregulatory protein in Streptococcus mutans modulates the expression of multiple genes, including the sloABC operon that encodes essential Mn transport and genes that promote cariogenesis. In this study, we report on SloC- and SloR-deficient strains of S. mutans (GMS284 and GMS584, respectively) that demonstrate compromised survivorship compared with their UA159 wild-type progenitor and their complemented strains (GMS285 and GMS585, respectively), when challenged with streptonigrin and/or in growth competition experiments. The results of streptonigrin assays revealed significantly larger zones of inhibition for GMS584 than for either UA159 or GMS585, indicating weakened S. mutans survivorship in the absence of SloR. Competition assays revealed a compromised ability for GMS284 and GMS584 to survive peroxide challenge compared with their SloC- and SloR-proficient counterparts. These findings are consistent with a role for SloC and SloR in S. mutans aerotolerance. We also predicted differential expression of oxidative stress tolerance genes in GMS584 versus UA159 and GMS585 when grown aerobically. The results of quantitative RT-PCR experiments revealed S. mutans sod, tpx, and sloC expression that was upregulated in GMS584 compared with UA159 and GMS585, indicating that the impact of oxidative stress on S. mutans is more severe in the absence of SloR than in its presence. The results of electrophoretic mobility shift assays indicate that SloR does not bind to the sod or tpx promoter regions directly, implicating intermediaries that may arbitrate the SloR response to oxidative stress.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Regulação Bacteriana da Expressão Gênica
Estresse Oxidativo
Streptococcus mutans/genética
Streptococcus mutans/fisiologia
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
DNA Bacteriano
Teste de Complementação Genética
Peróxido de Hidrogênio/farmacologia
Metais
Mutação
Estresse Oxidativo/genética
Streptococcus mutans/efeitos dos fármacos
Streptococcus mutans/patogenicidade
Estreptonigrina/farmacologia
Superóxido Dismutase-1/genética
Virulência/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (DNA, Bacterial); 0 (Metals); 261Q3JB310 (Streptonigrin); BBX060AN9V (Hydrogen Peroxide); EC 1.15.1.1 (Superoxide Dismutase-1)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170529
[Lr] Data última revisão:
170529
[Sb] Subgrupo de revista:D
[Da] Data de entrada para processamento:151119
[St] Status:MEDLINE
[do] DOI:10.1111/omi.12147


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[PMID]:25006810
[Au] Autor:Tobe T; Yen H; Takahashi H; Kagayama Y; Ogasawara N; Oshima T
[Ad] Endereço:Department of Biomedical Informatics, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
[Ti] Título:Antisense transcription regulates the expression of the enterohemorrhagic Escherichia coli virulence regulatory gene ler in response to the intracellular iron concentration.
[So] Source:PLoS One;9(7):e101582, 2014.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Enteric pathogens, such as enterohemorrhagic E. coli (EHEC) O157:H7, encounter varying concentrations of iron during their life cycle. In the gastrointestinal tract, the amount of available free iron is limited because of absorption by host factors. EHEC and other enteric pathogens have developed sophisticated iron-responsive systems to utilize limited iron resources, and these systems are primarily regulated by the Fur repressor protein. The iron concentration could be a signal that controls gene expression in the intestines. In this study, we explored the role of iron in LEE (locus for enterocyte effacement) virulence gene expression in EHEC. In contrast to the expression of Fur-regulated genes, the expression of LEE genes was greatly reduced in fur mutants irrespective of the iron concentration. The expression of the ler gene, the LEE-encoded master regulator, was affected at a post-transcription step by fur mutation. Further analysis showed that the loss of Fur affected the translation of the ler gene by increasing the intracellular concentration of free iron, and the transcription of the antisense strand was necessary for regulation. The results indicate that LEE gene expression is closely linked to the control of intracellular free iron homeostasis.
[Mh] Termos MeSH primário: Escherichia coli O157/genética
Proteínas de Escherichia coli/genética
Regulação Bacteriana da Expressão Gênica
Ferro/metabolismo
Transativadores/genética
Transcrição Genética
[Mh] Termos MeSH secundário: Antibacterianos/farmacologia
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Farmacorresistência Bacteriana
Escherichia coli O157/metabolismo
Escherichia coli O157/patogenicidade
Proteínas de Escherichia coli/metabolismo
Ferritinas/fisiologia
Expressão Gênica
Oligorribonucleotídeos Antissenso/genética
Fosfoproteínas/genética
Fosfoproteínas/metabolismo
Interferência de RNA
Regulon
Proteínas Repressoras/genética
Proteínas Repressoras/metabolismo
Estreptonigrina/farmacologia
Transativadores/metabolismo
Virulência/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Escherichia coli Proteins); 0 (LEE protein, E coli); 0 (Ler protein, E coli); 0 (Oligoribonucleotides, Antisense); 0 (Phosphoproteins); 0 (Repressor Proteins); 0 (Trans-Activators); 0 (ferric uptake regulating proteins, bacterial); 261Q3JB310 (Streptonigrin); 9007-73-2 (Ferritins); E1UOL152H7 (Iron)
[Em] Mês de entrada:1503
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140710
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0101582


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[PMID]:24894858
[Au] Autor:Kobayashi S; Maki T; Kobayashi T; Hamaguchi M; Yoshikawa M; Sakamoto N; Iguchi A
[Ad] Endereço:The Department of Urology, National Kyushu Medical Center.
[Ti] Título:[Significance of the antimicrobial drug used to prevent febrile infection following prostate needle biopsy].
[So] Source:Hinyokika Kiyo;60(5):227-30, 2014 May.
[Is] ISSN:0018-1994
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo:The rate of incidence of febrile infection and the antimicrobial drug used at the time of prostate needle biopsy was examined retrospectively. SPFX (sparfloxacin) 400 mg (January 2007 to March 2010) and LVFX (levofloxacin) 500 mg (April 2010, onward) were administered prophylactically in 1,034 patients undergoing transrectal or transperineal prostate biopsy. One febrile infection occurred and resolved in each group. A single dose of LVFX 500 mg before the procedure effectively prevented febrile infection in both transrectal and transperineal prostate needle biopsy.
[Mh] Termos MeSH primário: Anti-Infecciosos/uso terapêutico
Biópsia por Agulha/efeitos adversos
Fluoroquinolonas/uso terapêutico
Controle de Infecções/métodos
Levofloxacino/uso terapêutico
Próstata/patologia
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Febre/prevenção & controle
Seres Humanos
Masculino
Meia-Idade
Estudos Retrospectivos
Estreptonigrina
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Infective Agents); 0 (Fluoroquinolones); 0 (retrostatin); 261Q3JB310 (Streptonigrin); 6GNT3Y5LMF (Levofloxacin); Q90AGA787L (sparfloxacin)
[Em] Mês de entrada:1408
[Cu] Atualização por classe:140604
[Lr] Data última revisão:
140604
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140605
[St] Status:MEDLINE


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[PMID]:24732643
[Au] Autor:Pan QX; Zhang JH; Su ZJ; Wang CR; Ke SY
[Ad] Endereço:Department of Oncosurgery, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, Fujian, China.
[Ti] Título:The Glasgow Prognostic Score is an independent prognostic predictor of hepatocellular carcinoma following radical resection.
[So] Source:Oncol Res Treat;37(4):192-7, 2014.
[Is] ISSN:2296-5262
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Some prognostic evaluation systems were developed to postoperatively predict the outcome of hepatocellular carcinoma (HCC) patients, mainly based on the cancer itself and the underlying liver diseases. However, none of these prognostic evaluation systems have so far been universally accepted. A simple and feasible scoring system is still lacking for the prediction of prognosis of HCC patients following resection. We aimed to uncover the correlation between the preoperative Glasgow Prognostic Score (GPS) and the clinical outcome of HCC patients after radical resection. METHODS: The patients were separated into 3 subgroups on the basis of their GPSs. The prognostic significance of the GPS in the patient cohort was evaluated by survival analysis. RESULTS: On univariate analysis, the levels of C-reactive protein and albumin, the Child-Pugh class, vascular invasion, tumor number, tumor size, the tumor/node/metastasis (TNM) stage, and the GPS were associated with overall survival and time to recurrence of HCC patients after radical resection. On multivariate analysis, the tumor size, albumin level, and GPS were independently associated with the outcome of HCC postoperatively. CONCLUSION: The GPS is an independent biomarker for prognostic prediction of HCC following radical resection.
[Mh] Termos MeSH primário: Proteína C-Reativa/análise
Carcinoma Hepatocelular/mortalidade
Carcinoma Hepatocelular/cirurgia
Hipoalbuminemia/mortalidade
Neoplasias Hepáticas/mortalidade
Neoplasias Hepáticas/cirurgia
Avaliação de Resultados (Cuidados de Saúde)/métodos
[Mh] Termos MeSH secundário: Carcinoma Hepatocelular/diagnóstico
China/epidemiologia
Comorbidade
Feminino
Hepatectomia
Seres Humanos
Hipoalbuminemia/sangue
Neoplasias Hepáticas/diagnóstico
Masculino
Meia-Idade
Prevalência
Prognóstico
Reprodutibilidade dos Testes
Medição de Risco
Sensibilidade e Especificidade
Albumina Sérica/análise
Estreptonigrina
Taxa de Sobrevida
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Serum Albumin); 0 (retrostatin); 261Q3JB310 (Streptonigrin); 9007-41-4 (C-Reactive Protein)
[Em] Mês de entrada:1412
[Cu] Atualização por classe:140415
[Lr] Data última revisão:
140415
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140416
[St] Status:MEDLINE
[do] DOI:10.1159/000361082


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[PMID]:24704534
[Au] Autor:Becerra G; Merchán F; Blasco R; Igeño MI
[Ad] Endereço:Departamento de Bioquímica y Biología Molecular y Genética Facultad de Veterinaria, Universidad de Extremadura, Avenida de la Universidad s/n, 10003 Cáceres, Spain.
[Ti] Título:Characterization of a ferric uptake regulator (Fur)-mutant of the cyanotrophic bacterium Pseudomonas pseudoalcaligenes CECT5344.
[So] Source:J Biotechnol;190:2-10, 2014 Nov 20.
[Is] ISSN:1873-4863
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The Fur protein is the main sensor of cellular iron status in bacteria. In the present study, we inactivated the fur gene of Pseudomonas pseudoalcaligenes CECT5344 and characterized the resulting mutant. Our findings provide experimental evidence that, cyanide generates an intracellular signal equivalent to that triggered by iron deprivation, as witnessed by the induction of prrF and fiuA (ferrichrome receptor) expression in the presence of cyanide. The fur mutant also displayed slow growth, especially in minimal culture medium, increased sensitivity to cyanide in LB medium and as expected, resistance to manganese ions. Moreover, the mutant exhibited enhanced iron accumulation and increased sensitivity to streptonigrin, as well as to some inducers of oxidative stress, such as paraquat and menadione, yet it remained resistant to hydrogen peroxide. Surprisingly, neither the wild type strain nor the fur mutant strain produced siderophores that could be detected using the universal CAS-agar method.
[Mh] Termos MeSH primário: Proteínas de Bactérias/genética
Mutação
Pseudomonas pseudoalcaligenes/genética
Proteínas Repressoras/genética
[Mh] Termos MeSH secundário: Cianetos/metabolismo
Cianetos/farmacologia
Peróxido de Hidrogênio/farmacologia
Ferro/metabolismo
Estresse Oxidativo/efeitos dos fármacos
Fenótipo
Pseudomonas pseudoalcaligenes/crescimento & desenvolvimento
Pseudomonas pseudoalcaligenes/metabolismo
Estreptonigrina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Cyanides); 0 (Repressor Proteins); 0 (ferric uptake regulating proteins, bacterial); 261Q3JB310 (Streptonigrin); BBX060AN9V (Hydrogen Peroxide); E1UOL152H7 (Iron)
[Em] Mês de entrada:1507
[Cu] Atualização por classe:141203
[Lr] Data última revisão:
141203
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140408
[St] Status:MEDLINE


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[PMID]:24656606
[Au] Autor:Boulay C; Jacquemier M; Pomero V; Castanier E; Authier G; Chabrol B; Bollini G; Jouve JL; Viehweger E
[Ad] Endereço:Laboratoire de la marche, service de chirurgie orthopédique pédiatrique, CHU La Timone-Enfants, 264, rue Saint-Pierre, 13385 Marseille cedex 05, France; Service de neurologie pédiatrique, CHU La Timone-Enfants, 13385 Marseille, France; Institut des sciences du mouvement, Aix-Marseille université, UM
[Ti] Título:Dynamic EMG of peroneus longus in hemiplegic children with equinovarus.
[So] Source:Ann Phys Rehabil Med;57(3):185-92, 2014 Apr.
[Is] ISSN:1877-0665
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: In hemiplegic children the appearance of equinovarus is correlated with premature electromyography (EMG) activity of the gastrocnemius medialis (GM) prior to initial contact. The goal was to analyze the onset of EMG activation in the GM and, more particularly, the peroneus longus (PL) in cases of equinovarus: is PL activity likewise premature? MATERIAL AND METHODS: As 15 hemiplegic children (age 5 years±1.5) with equinovarus walked, their PL and GM EMG activity was being recorded. The latter was normalized in terms of gait cycle percentage (0-100%) and detected through semi-automatic selection with activation threshold set at 20µV. A paired t-test compared activation onset of the PL versus the GM muscles. RESULTS: As regards the healthy limb, activity onset of the GM (+14.55%) and the PL (+19.2%) muscles occurred only during the ST. In cases of equinovarus, activation of the GM (-5.2%) and the PL (-6.1%) occurred during the SW and was premature. For each muscle, comparison between the healthy and the hemiplegic side was highly significant (P<0.001). CONCLUSION: Premature PL and GM EMG activity preceding initial contact corresponds not to a disorder secondary to imbalance but rather, more probably, to motor command dysfunction. While the PL consequently contributes to equinus deformity, its possible role in varus genesis is less evident. EMG study needs to be completed by comparing PL and tibialis posterior strength while taking foot bone morphology into full account.
[Mh] Termos MeSH primário: Paralisia Cerebral/fisiopatologia
Pé Torto Equinovaro/fisiopatologia
Hemiplegia/fisiopatologia
Músculo Esquelético/fisiopatologia
[Mh] Termos MeSH secundário: Paralisia Cerebral/complicações
Criança
Pré-Escolar
Pé Torto Equinovaro/complicações
Eletromiografia
Feminino
Marcha/fisiologia
Hemiplegia/complicações
Seres Humanos
Masculino
Estreptonigrina
Caminhada/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (retrostatin); 261Q3JB310 (Streptonigrin)
[Em] Mês de entrada:1504
[Cu] Atualização por classe:140505
[Lr] Data última revisão:
140505
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140325
[St] Status:MEDLINE


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[PMID]:24595456
[Au] Autor:Sztiller-Sikorska M; Koprowska K; Majchrzak K; Hartman M; Czyz M
[Ad] Endereço:Department of Molecular Biology of Cancer, Medical University of Lodz, Lodz, Poland.
[Ti] Título:Natural compounds' activity against cancer stem-like or fast-cycling melanoma cells.
[So] Source:PLoS One;9(3):e90783, 2014.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Accumulating evidence supports the concept that melanoma is highly heterogeneous and sustained by a small subpopulation of melanoma stem-like cells. Those cells are considered as responsible for tumor resistance to therapies. Moreover, melanoma cells are characterized by their high phenotypic plasticity. Consequently, both melanoma stem-like cells and their more differentiated progeny must be eradicated to achieve durable cure. By reevaluating compounds in heterogeneous melanoma populations, it might be possible to select compounds with activity not only against fast-cycling cells but also against cancer stem-like cells. Natural compounds were the focus of the present study. METHODS: We analyzed 120 compounds from The Natural Products Set II to identify compounds active against melanoma populations grown in an anchorage-independent manner and enriched with cells exerting self-renewing capacity. Cell viability, cell cycle arrest, apoptosis, gene expression, clonogenic survival and label-retention were analyzed. FINDINGS: Several compounds efficiently eradicated cells with clonogenic capacity and nanaomycin A, streptonigrin and toyocamycin were effective at 0.1 µM. Other anti-clonogenic but not highly cytotoxic compounds such as bryostatin 1, siomycin A, illudin M, michellamine B and pentoxifylline markedly reduced the frequency of ABCB5 (ATP-binding cassette, sub-family B, member 5)-positive cells. On the contrary, treatment with maytansine and colchicine selected for cells expressing this transporter. Maytansine, streptonigrin, toyocamycin and colchicine, even if highly cytotoxic, left a small subpopulation of slow-dividing cells unaffected. Compounds selected in the present study differentially altered the expression of melanocyte/melanoma specific microphthalmia-associated transcription factor (MITF) and proto-oncogene c-MYC. CONCLUSION: Selected anti-clonogenic compounds might be further investigated as potential adjuvants targeting melanoma stem-like cells in the combined anti-melanoma therapy, whereas selected cytotoxic but not anti-clonogenic compounds, which increased the frequency of ABCB5-positive cells and remained slow-cycling cells unaffected, might be considered as a tool to enrich cultures with cells exhibiting melanoma stem cell characteristics.
[Mh] Termos MeSH primário: Produtos Biológicos/farmacologia
Descoberta de Drogas/métodos
Melanoma/tratamento farmacológico
Células-Tronco Neoplásicas/efeitos dos fármacos
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Ensaio de Unidades Formadoras de Colônias
Regulação da Expressão Gênica/genética
Seres Humanos
Fator de Transcrição Associado à Microftalmia
Naftoquinonas/farmacologia
Estreptonigrina/farmacologia
Toiocamicina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biological Products); 0 (Microphthalmia-Associated Transcription Factor); 0 (Naphthoquinones); 261Q3JB310 (Streptonigrin); 52934-83-5 (nanaomycin A); L7995C4D7F (Toyocamycin)
[Em] Mês de entrada:1411
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140306
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0090783


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[PMID]:24522728
[Au] Autor:Xia X; Lin S; Xia XX; Cong FS; Zhong JJ
[Ad] Endereço:State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, 200240, China.
[Ti] Título:Significance of agitation-induced shear stress on mycelium morphology and lavendamycin production by engineered Streptomyces flocculus.
[So] Source:Appl Microbiol Biotechnol;98(10):4399-407, 2014 May.
[Is] ISSN:1432-0614
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Lavendamycin methyl ester (LME) is a derivative of a highly functionalized aminoquinone alkaloid lavendamycin and could be used as a scaffold for novel anticancer agent development. This work demonstrated LME production by cultivation of an engineered strain of Streptomyces flocculus CGMCC4.1223 ΔstnB1, while the wild-type strain did not produce. To enhance its production, the effect of shear stress and oxygen supply on ΔstnB1 strain cultivation was investigated in detail. In flask culture, when the shaking speed increased from 150 to 220 rpm, the mycelium was altered from a large pellet to a filamentous hypha, and the LME production was almost doubled, while no significant differences were observed among varied filling volumes, which implied a crucial role of shear stress in the morphology and LME production. To confirm this suggestion, experiments with agitation speed ranging from 400 to 1,000 rpm at a fixed aeration rate of 1.0 vvm were conducted in a stirred tank bioreactor. It was found that the morphology became more hairy with reduced pellet size, and the LME production was enhanced threefolds when the agitation speed increased from 400 to 800 rpm. Further experiments by varying initial k L a value at the same agitation speed indicated that oxygen supply only slightly affected the physiological status of ΔstnB1 strain. Altogether, shear stress was identified as a major factor affecting the cell morphology and LME production. The work would be helpful to the production of LME and other secondary metabolites by filamentous microorganism cultivation.
[Mh] Termos MeSH primário: Antibióticos Antineoplásicos/metabolismo
Streptomyces/citologia
Streptomyces/metabolismo
Estreptonigrina/análogos & derivados
Estresse Mecânico
[Mh] Termos MeSH secundário: Fenômenos Mecânicos
Oxigênio/metabolismo
Streptomyces/genética
Streptomyces/fisiologia
Estreptonigrina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 261Q3JB310 (Streptonigrin); 81645-09-2 (lavendamycin); S88TT14065 (Oxygen)
[Em] Mês de entrada:1412
[Cu] Atualização por classe:140430
[Lr] Data última revisão:
140430
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140214
[St] Status:MEDLINE
[do] DOI:10.1007/s00253-014-5555-4



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