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[PMID]:29367529
[Au] Autor:Tamura M; Kitano M; Azuma K; Tsuboi K; Abe T; Ogita C; Yokoyama Y; Furukawa T; Yoshikawa T; Saito A; Nishioka A; Sekiguchi M; Azuma N; Tsunoda S; Hosono Y; Nakashima R; Ohmura K; Matsui K; Mimori T; Sano H
[Ad] Endereço:Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine.
[Ti] Título:[A case of anti-PL-7 antibody positive polymyositis with thrombotic microangiopathy].
[So] Source:Nihon Rinsho Meneki Gakkai Kaishi;40(6):450-455, 2017.
[Is] ISSN:1349-7413
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo:  A 65-year-old woman with a 17-year history of polymyositis and 8-year history of rheumatoid arthritis who was treated with a low dose of prednisolone and tacrolimus (Tac) was admitted to our hospital because of general malaise and hypertension. Blood tests showed thrombocytopenia, hemolytic anemia with fragmented erythrocytes, and hypercreatinemia. Based on these clinical features, she was diagnosed with thrombotic micro-angiopathy (TMA). Thrombocytopenia and hemolytic anemia with fragmented erythrocytes improved with the discontinuation of Tac and plasma exchange; however, hypertension and renal dysfunction persisted. TMA due to calcineurin inhibitor (CNI) nephropathy was suspected based on the histopathological findings of renal biopsy. However, the condition was atypical of a CNI nephropathy because the trough level of Tac was lower than that reported previously and renal dysfunction persisted after drug discontinuation. She had mild sclerodactylia and Raynaud's symptoms, although the diagnostic criteria for systemic sclerosis (SSc) were not satisfied. Moreover, the patient tested positive for anti PL-7 antibody. The relationship between anti PL-7 antibody and pathogenesis of SSc has been reported. In this case, it was suspected that CNI nephropathy worsened because of the potential basic factors of SSc. These findings indicate that TMA may occur in patients testing positive for anti PL-7 antibody who are treated with Tac.
[Mh] Termos MeSH primário: Aminoacil-tRNA Sintetases/imunologia
Autoanticorpos/sangue
Polimiosite/complicações
Microangiopatias Trombóticas/etiologia
[Mh] Termos MeSH secundário: Idoso
Artrite Reumatoide/complicações
Artrite Reumatoide/terapia
Biomarcadores/sangue
Inibidores de Calcineurina/administração & dosagem
Inibidores de Calcineurina/efeitos adversos
Feminino
Seres Humanos
Troca Plasmática
Polimiosite/diagnóstico
Polimiosite/terapia
Tacrolimo/administração & dosagem
Tacrolimo/efeitos adversos
Microangiopatias Trombóticas/diagnóstico
Suspensão de Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autoantibodies); 0 (Biomarkers); 0 (Calcineurin Inhibitors); EC 6.1.1.- (Amino Acyl-tRNA Synthetases); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180126
[St] Status:MEDLINE
[do] DOI:10.2177/jsci.40.450


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[PMID]:28461123
[Au] Autor:Tanizawa K; Handa T; Nakashima R; Kubo T; Hosono Y; Watanabe K; Aihara K; Ikezoe K; Sokai A; Nakatsuka Y; Taguchi Y; Hatta K; Noma S; Kobashi Y; Yoshizawa A; Oga T; Hirai T; Chin K; Nagai S; Izumi T; Mimori T; Mishima M
[Ad] Endereço:Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
[Ti] Título:The long-term outcome of interstitial lung disease with anti-aminoacyl-tRNA synthetase antibodies.
[So] Source:Respir Med;127:57-64, 2017 Jun.
[Is] ISSN:1532-3064
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Anti-aminoacyl transfer RNA synthetase antibodies (anti-ARS) are a group of myositis-specific autoantibodies that are detected in the sera of patients with polymyositis and dermatomyositis (PM/DM) and also in those of patients with idiopathic interstitial pneumonias without any connective tissue disease (CTD), including PM/DM. Although we reported the clinical characteristics of interstitial lung disease with anti-ARS antibodies (ARS-ILD) with and without PM/DM, the long-term prognosis of ARS-ILD remains undetermined. As our previous studies revealed that ARS-ILD without PM/DM was similar to CTD-associated ILD, and that ARS-ILD with PM/DM was radiologically suggestive of a nonspecific interstitial pneumonia (NSIP) pathological pattern, we hypothesized that the prognosis of ARS-ILD might be distinct from that of idiopathic pulmonary fibrosis (IPF) without anti-ARS. OBJECTIVES: To elucidate the long-term outcome of ARS-ILD with and without PM/DM and compare it to that of IPF. METHODS: A two-center retrospective study was conducted. The study population comprised 36 patients with ARS-ILD (8 with PM, 12 with DM, and 16 without myositis throughout the course), 100 patients with IPF without anti-ARS, and 7 patients with NSIP without anti-ARS. The presence of anti-ARS was determined by RNA immunoprecipitation using the sera obtained at the time of diagnosis before specific treatment. MEASUREMENTS AND MAIN RESULTS: During the observational period (median 49 months; range, 1-114 months), 7 patients with ARS-ILD (19%; 3 with PM, 1 with DM, and 3 without PM/DM) and 51 patients with IPF (51%) died. Patients with ARS-ILD had better overall survival than those with IPF (log-rank test, P < 0.001) and similar survival compared to those with NSIP (log-rank test, P = 0.59). The prognosis for patients with ARS-ILD was similar between those with and without myositis (log-rank test, P = 0.91). At the median follow-up time of 76.5 months, 14 of the 36 patients with ARS-ILD had deteriorated. Both a decline in forced vital capacity or an initiation of long-term oxygen therapy during the course (odds ratio [OR], 5.34) and acute exacerbation (OR, 28.4) significantly increased the mortality risk. CONCLUSIONS: The long-term outcome of ARS-ILD was significantly better than that of IPF regardless of the presence or absence of myositis.
[Mh] Termos MeSH primário: Aminoacil-tRNA Sintetases/imunologia
Autoanticorpos/sangue
Dermatomiosite/complicações
Fibrose Pulmonar Idiopática/imunologia
Doenças Pulmonares Intersticiais/imunologia
Miosite/imunologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Autoanticorpos/imunologia
Doenças do Tecido Conjuntivo/complicações
Doenças do Tecido Conjuntivo/diagnóstico
Doenças do Tecido Conjuntivo/imunologia
Doenças do Tecido Conjuntivo/mortalidade
Dermatomiosite/imunologia
Dermatomiosite/mortalidade
Feminino
Seres Humanos
Oxigenação Hiperbárica/métodos
Fibrose Pulmonar Idiopática/complicações
Fibrose Pulmonar Idiopática/diagnóstico por imagem
Doenças Pulmonares Intersticiais/diagnóstico por imagem
Doenças Pulmonares Intersticiais/mortalidade
Masculino
Meia-Idade
Mortalidade
Miosite/mortalidade
Estudos Observacionais como Assunto
Avaliação de Resultados (Cuidados de Saúde)
Prognóstico
RNA/imunologia
Estudos Retrospectivos
Análise de Sobrevida
Capacidade Vital/fisiologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autoantibodies); 63231-63-0 (RNA); EC 6.1.1.- (Amino Acyl-tRNA Synthetases)
[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:170503
[St] Status:MEDLINE


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[PMID]:27777026
[Au] Autor:Cantara WA; Olson ED; Musier-Forsyth K
[Ad] Endereço:Department of Chemistry and Biochemistry, Center for Retrovirus Research, and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, United States.
[Ti] Título:Analysis of RNA structure using small-angle X-ray scattering.
[So] Source:Methods;113:46-55, 2017 Jan 15.
[Is] ISSN:1095-9130
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In addition to their role in correctly attaching specific amino acids to cognate tRNAs, aminoacyl-tRNA synthetases (aaRS) have been found to possess many alternative functions and often bind to and act on other nucleic acids. In contrast to the well-defined 3D structure of tRNA, the structures of many of the other RNAs recognized by aaRSs have not been solved. Despite advances in the use of X-ray crystallography (XRC), nuclear magnetic resonance (NMR) spectroscopy and cryo-electron microscopy (cryo-EM) for structural characterization of biomolecules, significant challenges to solving RNA structures still exist. Recently, small-angle X-ray scattering (SAXS) has been increasingly employed to characterize the 3D structures of RNAs and RNA-protein complexes. SAXS is capable of providing low-resolution tertiary structure information under physiological conditions and with less intensive sample preparation and data analysis requirements than XRC, NMR and cryo-EM. In this article, we describe best practices involved in the process of RNA and RNA-protein sample preparation, SAXS data collection, data analysis, and structural model building.
[Mh] Termos MeSH primário: Aminoacil-tRNA Sintetases/metabolismo
Escherichia coli/genética
Dobramento de RNA
RNA de Transferência Aminoácido-Específico/química
Aminoacilação de RNA de Transferência
[Mh] Termos MeSH secundário: Aminoácidos/metabolismo
Aminoacil-tRNA Sintetases/genética
Cromatografia em Gel
Escherichia coli/metabolismo
Modelos Moleculares
Eletroforese em Gel de Poliacrilamida Nativa
Plasmídeos/química
Plasmídeos/metabolismo
Ligação Proteica
RNA de Transferência Aminoácido-Específico/genética
RNA de Transferência Aminoácido-Específico/metabolismo
Espalhamento a Baixo Ângulo
Difração de Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (RNA, Transfer, Amino Acid-Specific); EC 6.1.1.- (Amino Acyl-tRNA Synthetases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161030
[St] Status:MEDLINE


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[PMID]:27775882
[Au] Autor:Kipper K; Lundius EG; Curic V; Nikic I; Wiessler M; Lemke EA; Elf J
[Ad] Endereço:Department of Molecular and Cell Biology, Science for Life Laboratory, Uppsala University , Se-751 24 Uppsala, Sweden.
[Ti] Título:Application of Noncanonical Amino Acids for Protein Labeling in a Genomically Recoded Escherichia coli.
[So] Source:ACS Synth Biol;6(2):233-255, 2017 Feb 17.
[Is] ISSN:2161-5063
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Small synthetic fluorophores are in many ways superior to fluorescent proteins as labels for imaging. A major challenge is to use them for a protein-specific labeling in living cells. Here, we report on our use of noncanonical amino acids that are genetically encoded via the pyrrolysyl-tRNA/pyrrolysyl-RNA synthetase pair at artificially introduced TAG codons in a recoded E. coli strain. The strain is lacking endogenous TAG codons and the TAG-specific release factor RF1. The amino acids contain bioorthogonal groups that can be clicked to externally supplied dyes, thus enabling protein-specific labeling in live cells. We find that the noncanonical amino acid incorporation into the target protein is robust for diverse amino acids and that the usefulness of the recoded E. coli strain mainly derives from the absence of release factor RF1. However, the membrane permeable dyes display high nonspecific binding in intracellular environment and the electroporation of hydrophilic nonmembrane permeable dyes severely impairs growth of the recoded strain. In contrast, proteins exposed on the outer membrane of E. coli can be labeled with hydrophilic dyes with a high specificity as demonstrated by labeling of the osmoporin OmpC. Here, labeling can be made sufficiently specific to enable single molecule studies as exemplified by OmpC single particle tracking.
[Mh] Termos MeSH primário: Aminoácidos/genética
Escherichia coli/genética
Genoma Bacteriano/genética
Proteínas/genética
[Mh] Termos MeSH secundário: Aminoacil-tRNA Sintetases
Códon de Terminação/genética
Corantes Fluorescentes
Genômica/métodos
RNA de Transferência/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (Codon, Terminator); 0 (Fluorescent Dyes); 0 (Proteins); 9014-25-9 (RNA, Transfer); EC 6.1.1.- (Amino Acyl-tRNA Synthetases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1021/acssynbio.6b00138


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[PMID]:29065190
[Au] Autor:Shibata A; Kuno M; Adachi R; Sato Y; Hattori H; Matsuda A; Okuzono Y; Igaki K; Tominari Y; Takagi T; Yabuki M; Okaniwa M
[Ad] Endereço:Immunology Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa, Japan.
[Ti] Título:Discovery and pharmacological characterization of a new class of prolyl-tRNA synthetase inhibitor for anti-fibrosis therapy.
[So] Source:PLoS One;12(10):e0186587, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Scleroderma has clinical characteristics including skin and other tissue fibrosis, but there is an unmet need for anti-fibrotic therapy. Halofuginone (HF) is a well-known anti-fibrosis agent in preclinical and clinical studies which exerts its effect via inhibition of TGF-ß/Smad3 signaling pathway. Recently, prolyl-tRNA synthetase (PRS) was elucidated as a target protein for HF that binds to the proline binding site of the catalytic domain of PRS. Here, we characterized a new class of PRS inhibitor (T-3833261) that is carefully designed in a way that binds to the ATP site of the catalytic domain and does not disrupt binding of proline. The anti-fibrotic activity and the mechanism of action for T-3833261 on TGF-ß-induced fibrotic assay were compared with those of HF in primary human skin fibroblast. We evaluated in vivo effect of topical application of T-3833261 and HF on TGF-ß-induced fibrotic genes expression in mice. We found that T-3833261 suppressed TGF-ß-induced α-smooth muscle actin (α-SMA) and type I collagen α1 (COL1A1) expression through the Smad3 axis in a similar fashion to HF. In vivo topical application of T-3833261 reduced the increase of fibrotic genes expression such as α-Sma, Col1a1 and Col1a2 by TGF-ß intradermal injection to the ear of a mouse. We revealed that T-3833261 is more effective than HF under the conditions of high proline concentration, as reported in fibrotic tissues. These results suggest the potential of ATP competitive PRS inhibitors for the treatment of fibrotic diseases such as scleroderma.
[Mh] Termos MeSH primário: Aminoacil-tRNA Sintetases/antagonistas & inibidores
Inibidores Enzimáticos/farmacologia
Escleroderma Sistêmico/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Descoberta de Drogas
Inibidores Enzimáticos/uso terapêutico
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos C3H
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); EC 6.1.1.- (Amino Acyl-tRNA Synthetases); EC 6.1.1.15 (prolyl T RNA synthetase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171025
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186587


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[PMID]:28758722
[Au] Autor:Lopatniuk M; Myronovskyi M; Luzhetskyy A
[Ad] Endereço:Department of Pharmaceutical Biotechnology, Saarland University , 66123 Saarbrücken, Germany.
[Ti] Título:Streptomyces albus: A New Cell Factory for Non-Canonical Amino Acids Incorporation into Ribosomally Synthesized Natural Products.
[So] Source:ACS Chem Biol;12(9):2362-2370, 2017 Sep 15.
[Is] ISSN:1554-8937
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The incorporation of noncanonical amino acids (ncAAs) with different side chains into a peptide is a promising technique for changing the functional properties of that peptide. Of particular interest is the incorporation of ncAAs into peptide-derived natural products to optimize their biophysical properties for medical and industrial applications. Here, we present the first instance of ncAA incorporation into the natural product cinnamycin in streptomycetes using the orthogonal pyrrolysyl-tRNA synthetase/tRNA pair from Methanosarcina barkeri. This approach allows site-specific incorporation of ncAAs via the read-through of a stop codon by the suppressor tRNA , which can carry different pyrrolysine analogues. Five new deoxycinnamycin derivatives were obtained with three distinct pyrrolysine analogues incorporated into diverse positions of the antibiotic. The combination of partial hydrolysis and MS/MS fragmentation analysis was used to verify the exact position of the incorporation events. The introduction of ncAAs into different positions of the peptide had opposite effects on the peptide's biological activity.
[Mh] Termos MeSH primário: Aminoacil-tRNA Sintetases/metabolismo
Bacteriocinas/metabolismo
Produtos Biológicos/metabolismo
Lisina/análogos & derivados
Methanosarcina barkeri/enzimologia
Peptídeos Cíclicos/metabolismo
Streptomyces/metabolismo
[Mh] Termos MeSH secundário: Aminoacil-tRNA Sintetases/genética
Bacteriocinas/química
Bacteriocinas/genética
Produtos Biológicos/química
Clonagem Molecular
Microbiologia Industrial
Lisina/química
Lisina/genética
Lisina/metabolismo
Methanosarcina barkeri/genética
Methanosarcina barkeri/metabolismo
Família Multigênica
Peptídeos Cíclicos/química
Peptídeos Cíclicos/genética
Biossíntese de Proteínas
Ribossomos/genética
Ribossomos/metabolismo
Streptomyces/química
Streptomyces/citologia
Streptomyces/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacteriocins); 0 (Biological Products); 0 (Peptides, Cyclic); 1405-39-6 (cinnamycin); EC 6.1.1.- (Amino Acyl-tRNA Synthetases); H3214Y96LP (pyrrolysine); K3Z4F929H6 (Lysine)
[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:170801
[St] Status:MEDLINE
[do] DOI:10.1021/acschembio.7b00359


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[PMID]:28758366
[Au] Autor:Brabham R; Fascione MA
[Ad] Endereço:York Structural Biology Laboratory, Department of Chemistry, University of York, Heslington Road, York, YO10 5DD, UK.
[Ti] Título:Pyrrolysine Amber Stop-Codon Suppression: Development and Applications.
[So] Source:Chembiochem;18(20):1973-1983, 2017 Oct 18.
[Is] ISSN:1439-7633
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The pyrrolysine tRNA synthetase-tRNA pair is probably one of the most promiscuous tRNA-synthetase pairs found in nature, capable of genetically encoding a plethora of noncanonical amino acids through stop codon reassignment. Proteins containing reactive handles, post-translational modification mimics or both can be produced in practical quantities, allowing inter alia the probing of biological pathways, generating antibody-drug conjugates and enhancing protein function. This Minireview summarises the development of pyrrolysine amber stop-codon suppression, presents some of the considerations required to utilise this technique to its greatest potential, and showcases the creative ways in which this technique has led to a better understanding of biological systems.
[Mh] Termos MeSH primário: Códon de Terminação/metabolismo
Lisina/análogos & derivados
[Mh] Termos MeSH secundário: Aminoacil-tRNA Sintetases/metabolismo
Química Click
Códon de Terminação/genética
Lisina/química
Lisina/metabolismo
Processamento de Proteína Pós-Traducional
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Codon, Terminator); EC 6.1.1.- (Amino Acyl-tRNA Synthetases); H3214Y96LP (pyrrolysine); K3Z4F929H6 (Lysine)
[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:170801
[St] Status:MEDLINE
[do] DOI:10.1002/cbic.201700148


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[PMID]:28650092
[Au] Autor:Hauf M; Richter F; Schneider T; Faidt T; Martins BM; Baumann T; Durkin P; Dobbek H; Jacobs K; Möglich A; Budisa N
[Ad] Endereço:Institut für Chemie, Technische Universität Berlin, Müller-Breslau-Strasse 10, 10623, Berlin, Germany.
[Ti] Título:Photoactivatable Mussel-Based Underwater Adhesive Proteins by an Expanded Genetic Code.
[So] Source:Chembiochem;18(18):1819-1823, 2017 Sep 19.
[Is] ISSN:1439-7633
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Marine mussels exhibit potent underwater adhesion abilities under hostile conditions by employing 3,4-dihydroxyphenylalanine (DOPA)-rich mussel adhesive proteins (MAPs). However, their recombinant production is a major biotechnological challenge. Herein, a novel strategy based on genetic code expansion has been developed by engineering efficient aminoacyl-transfer RNA synthetases (aaRSs) for the photocaged noncanonical amino acid ortho-nitrobenzyl DOPA (ONB-DOPA). The engineered ONB-DOPARS enables in vivo production of MAP type 5 site-specifically equipped with multiple instances of ONB-DOPA to yield photocaged, spatiotemporally controlled underwater adhesives. Upon exposure to UV light, these proteins feature elevated wet adhesion properties. This concept offers new perspectives for the production of recombinant bioadhesives.
[Mh] Termos MeSH primário: Bivalves/metabolismo
Código Genético/genética
Proteínas/metabolismo
[Mh] Termos MeSH secundário: Adesivos/efeitos da radiação
Aminoacil-tRNA Sintetases/metabolismo
Animais
Materiais Biomiméticos/metabolismo
Bivalves/genética
Di-Hidroxifenilalanina/metabolismo
Microscopia de Força Atômica
Microscopia de Varredura por Sonda
Mutagênese Sítio-Dirigida
Proteínas/genética
Proteínas Recombinantes/biossíntese
Proteínas Recombinantes/química
Proteínas Recombinantes/isolamento & purificação
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adhesives); 0 (Proteins); 0 (Recombinant Proteins); 0 (adhesive protein, mussel); 63-84-3 (Dihydroxyphenylalanine); EC 6.1.1.- (Amino Acyl-tRNA Synthetases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170627
[St] Status:MEDLINE
[do] DOI:10.1002/cbic.201700327


  9 / 4253 MEDLINE  
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[PMID]:28586844
[Au] Autor:Noguchi E; Uruha A; Suzuki S; Hamanaka K; Ohnuki Y; Tsugawa J; Watanabe Y; Nakahara J; Shiina T; Suzuki N; Nishino I
[Ad] Endereço:Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
[Ti] Título:Skeletal Muscle Involvement in Antisynthetase Syndrome.
[So] Source:JAMA Neurol;74(8):992-999, 2017 Aug 01.
[Is] ISSN:2168-6157
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: Antisynthetase syndrome, characterized by myositis, interstitial lung disease, skin rash, arthropathy, and Raynaud phenomenon, is a clinical entity based on the presence of aminoacyl transfer RNA synthetase (ARS) antibodies in patients' serum. However, antisynthetase syndrome is not included in the histological subsets of idiopathic inflammatory myopathies. Objective: To elucidate the clinical features of myositis in patients with antisynthetase syndrome. Design, Setting, and Participants: In this cohort study, muscle biopsy and blood samples were collected from 460 patients with idiopathic inflammatory myositis from various regional referral centers throughout Japan between October 2010 and December 2014. Data were analyzed in March 2016. Exposures: Six different anti-ARS antibodies were detected in serum by RNA immunoprecipitation. Line blot assay and protein immunoprecipitation were also performed. HLA-DRB1 alleles were genotyped. Main Outcomes and Measures: The main outcomes were muscle manifestations and histological findings. Predisposing factors, extramuscular symptoms, and follow-up information were also studied. Results: Of 460 patients with idiopathic inflammatory myopathies, 51 (11.1%) had anti-ARS antibodies. Of this subset, 31 (61%) were women, with a mean (SD) age at disease onset of 60.2 (16.1) years. Among 6 different anti-ARS antibodies, only 1-the anti-OJ antibody-was not detected by line blot assay but by RNA immunoprecipitation. There were no significant HLA-DRB1 alleles associated with anti-ARS antibodies. All 51 patients presented with muscle limb weakness; 14 (27%) had severe limb weakness, 17 (33%) had neck muscle weakness, 15 (29%) had dysphagia, and 15 (29%) had muscle atrophy. Although patients with anti-OJ antibodies showed severe muscle weakness, the clinical presentations of antisynthetase syndrome were relatively homogeneous. In histology, perifascicular necrosis, the characteristic finding of antisynthetase syndrome, was found in 24 patients (47%). Myositis with anti-ARS antibodies responded to the combination of immunosuppressive therapy with favorable outcomes. Interstitial lung disease, found in 41 patients (80%), was more closely associated with mortality than myositis. Conclusions and Relevance: Although clinical presentations of antisynthetase syndrome were relatively homogeneous, anti-OJ antibodies were associated with severe muscle involvement. Antisynthetase syndrome is a clinical and histological subset among idiopathic inflammatory myopathies.
[Mh] Termos MeSH primário: Músculo Esquelético/metabolismo
Miosite/complicações
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Aminoacil-tRNA Sintetases/imunologia
Autoanticorpos/sangue
Estudos de Coortes
Eletromiografia
Feminino
Genótipo
Cadeias HLA-DRB1/genética
Seres Humanos
Imunoprecipitação
Imagem por Ressonância Magnética
Masculino
Meia-Idade
Músculo Esquelético/diagnóstico por imagem
Músculo Esquelético/fisiopatologia
Miosite/genética
Miosite/imunologia
Miosite/patologia
Estatísticas não Paramétricas
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autoantibodies); 0 (HLA-DRB1 Chains); EC 6.1.1.- (Amino Acyl-tRNA Synthetases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170822
[Lr] Data última revisão:
170822
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170607
[St] Status:MEDLINE
[do] DOI:10.1001/jamaneurol.2017.0934


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[PMID]:28566605
[Au] Autor:Tokunaga K; Hagino N
[Ad] Endereço:Department of Rheumatology, Japanese Red Cross Kumamoto Hospital, Japan.
[Ti] Título:Dermatomyositis with Rapidly Progressive Interstitial Lung Disease Treated with Rituximab: A Report of 3 Cases in Japan.
[So] Source:Intern Med;56(11):1399-1403, 2017.
[Is] ISSN:1349-7235
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:We performed a retrospective chart review of three patients with hypomyopathic dermatomyositis and rapidly progressive interstitial lung disease. The patients were Japanese women of 71, 69, and 65 years of age. Two patients were anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive and 1 was anti-aminoacyl-tRNA synthetase (anti-ARS) antibody-positive. Their respiratory statuses deteriorated despite the administration of glucocorticoid, calcineurin inhibitors, and intravenous cyclophosphamide therapy. We subsequently administered rituximab. The anti-ARS antibody-positive patient survived, while 2 anti-MDA5 antibody-positive patients died.
[Mh] Termos MeSH primário: Dermatomiosite/complicações
Dermatomiosite/tratamento farmacológico
Fatores Imunológicos/uso terapêutico
Doenças Pulmonares Intersticiais/complicações
Rituximab/uso terapêutico
[Mh] Termos MeSH secundário: Idoso
Aminoacil-tRNA Sintetases/imunologia
Autoanticorpos
Inibidores de Calcineurina/uso terapêutico
Ciclofosfamida/uso terapêutico
Dermatomiosite/imunologia
Feminino
Glucocorticoides/uso terapêutico
Seres Humanos
Helicase IFIH1 Induzida por Interferon/imunologia
Japão
Doenças Pulmonares Intersticiais/tratamento farmacológico
Doenças Pulmonares Intersticiais/imunologia
Estudos Retrospectivos
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autoantibodies); 0 (Calcineurin Inhibitors); 0 (Glucocorticoids); 0 (Immunologic Factors); 4F4X42SYQ6 (Rituximab); 8N3DW7272P (Cyclophosphamide); EC 3.6.1.- (IFIH1 protein, human); EC 3.6.4.13 (Interferon-Induced Helicase, IFIH1); EC 6.1.1.- (Amino Acyl-tRNA Synthetases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170602
[St] Status:MEDLINE
[do] DOI:10.2169/internalmedicine.56.7956



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