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Pesquisa : D12.776.543.750.705.408.100.450 [Categoria DeCS]
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[PMID]:28916665
[Au] Autor:Cui LL; Nitzsche F; Pryazhnikov E; Tibeykina M; Tolppanen L; Rytkönen J; Huhtala T; Mu JW; Khiroug L; Boltze J; Jolkkonen J
[Ad] Endereço:From the Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland (L.-l.C., J.-w.M., J.J.); Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (F.N.); McGowan Institute for Regenerative Medicine, University of Pittsburgh
[Ti] Título:Integrin α4 Overexpression on Rat Mesenchymal Stem Cells Enhances Transmigration and Reduces Cerebral Embolism After Intracarotid Injection.
[So] Source:Stroke;48(10):2895-2900, 2017 Oct.
[Is] ISSN:1524-4628
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND PURPOSE: Very late antigen-4 (integrin α4ß1)/vascular cell adhesion molecule-1 mediates leukocyte trafficking and transendothelial migration after stroke. Mesenchymal stem cells (MSCs) typically express integrin ß1 but insufficient ITGA4 (integrin α4), which limits their homing after intravascular transplantation. We tested whether ITGA4 overexpression on MSCs increases cerebral homing after intracarotid transplantation and reduces MSC-borne cerebral embolism. METHODS: Rat MSCs were lentivirally transduced to overexpress ITGA4. In vitro transendothelial migration was assessed using a Boyden chamber assay. Male Wistar rats intracarotidly received 0.5×10 control or modified MSCs 24 hours after sham or stroke surgery. In vivo behavior of MSCs in the cerebral vasculature was observed by intravital microscopy and single-photon emission computed tomography for up to 72 hours. RESULTS: Transendothelial migration of ITGA4-overexpressing MSCs was increased in vitro. MSCs were passively entrapped in microvessels in vivo and occasionally formed large cell aggregates causing local blood flow interruptions. MSCs were rarely found in perivascular niches or parenchyma at 72 hours post-transplantation, but ITGA4 overexpression significantly decreased cell aggregation and ameliorated the evoked cerebral embolism in stroke rats. CONCLUSIONS: ITGA4 overexpression on MSCs enhances transendothelial migration in vitro, but not in vivo, although it improves safety after intracarotid transplantation into stroke rats.
[Mh] Termos MeSH primário: Integrina alfa4/administração & dosagem
Integrina alfa4/biossíntese
Embolia Intracraniana/terapia
Células Mesenquimais Estromais/metabolismo
Transplante de Células-Tronco/métodos
Migração Transendotelial e Transepitelial/fisiologia
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Expressão Gênica
Injeções Intra-Arteriais
Integrina alfa4/genética
Embolia Intracraniana/diagnóstico por imagem
Masculino
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
143198-26-9 (Integrin alpha4)
[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:170917
[St] Status:MEDLINE
[do] DOI:10.1161/STROKEAHA.117.017809


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[PMID]:28916537
[Au] Autor:Plavina T; Muralidharan KK; Kuesters G; Mikol D; Evans K; Subramanyam M; Nestorov I; Chen Y; Dong Q; Ho PR; Amarante D; Adams A; De Sèze J; Fox R; Gold R; Jeffery D; Kappos L; Montalban X; Weinstock-Guttman B; Hartung HP; Cree BAC
[Ad] Endereço:From Biogen (T.P., K.K.M., G.K., D.M., K.E., M.S., I.N., Y.C., Q.D., P.-R.H., D.A.), Cambridge, MA; Ashfield Healthcare Communications (A.A.), Middletown, CT; Hôpital Civil (J.D.S.), Strasbourg, France; Mellen Center for Multiple Sclerosis (R.F.), Cleveland Clinic, OH; St. Josef Hospital (R.G.), Ruh
[Ti] Título:Reversibility of the effects of natalizumab on peripheral immune cell dynamics in MS patients.
[So] Source:Neurology;89(15):1584-1593, 2017 Oct 10.
[Is] ISSN:1526-632X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To characterize the reversibility of natalizumab-mediated changes in pharmacokinetics/pharmacodynamics in patients with multiple sclerosis (MS) following therapy interruption. METHODS: Pharmacokinetic/pharmacodynamic data were collected in the Safety and Efficacy of Natalizumab in the Treatment of Multiple Sclerosis (AFFIRM) (every 12 weeks for 116 weeks) and Randomized Treatment Interruption of Natalizumab (RESTORE) (every 4 weeks for 28 weeks) studies. Serum natalizumab and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured using immunoassays. Lymphocyte subsets, α4-integrin expression/saturation, and vascular cell adhesion molecule-1 (VCAM-1) binding were assessed using flow cytometry. RESULTS: Blood lymphocyte counts (cells/L) in natalizumab-treated patients increased from 2.1 × 10 to 3.5 × 10 . Starting 8 weeks post last natalizumab dose, lymphocyte counts became significantly lower in patients interrupting treatment than in those continuing treatment (3.1 × 10 vs 3.5 × 10 ; = 0.031), plateauing at prenatalizumab levels from week 16 onward. All measured cell subpopulation, α4-integrin expression/saturation, and sVCAM changes demonstrated similar reversibility. Lymphocyte counts remained within the normal range. Ex vivo VCAM-1 binding to lymphocytes increased until ≈16 weeks after the last natalizumab dose, then plateaued, suggesting reversibility of immune cell functionality. The temporal appearance of gadolinium-enhancing lesions was consistent with pharmacodynamic marker reversal. CONCLUSIONS: Natalizumab's effects on peripheral immune cells and pharmacodynamic markers were reversible, with changes starting 8 weeks post last natalizumab dose; levels returned to those observed/expected in untreated patients ≈16 weeks post last dose. This reversibility differentiates natalizumab from MS treatments that require longer reconstitution times. Characterization of the time course of natalizumab's biological effects may help clinicians make treatment sequencing decisions. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the pharmacodynamic markers of natalizumab are reversed ≈16 weeks after stopping natalizumab.
[Mh] Termos MeSH primário: Fatores Imunológicos/uso terapêutico
Subpopulações de Linfócitos/imunologia
Esclerose Múltipla/tratamento farmacológico
Natalizumab/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Método Duplo-Cego
Feminino
Seguimentos
Seres Humanos
Fatores Imunológicos/sangue
Integrina alfa4/sangue
Contagem de Linfócitos
Subpopulações de Linfócitos/metabolismo
Masculino
Meia-Idade
Esclerose Múltipla/sangue
Natalizumab/sangue
Estudos Retrospectivos
Prevenção Secundária
Resultado do Tratamento
Molécula 1 de Adesão de Célula Vascular/sangue
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Immunologic Factors); 0 (Natalizumab); 0 (Vascular Cell Adhesion Molecule-1); 143198-26-9 (Integrin alpha4)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170917
[St] Status:MEDLINE
[do] DOI:10.1212/WNL.0000000000004485


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[PMID]:28736941
[Au] Autor:Sharma P; Sharma A; Srivastava M
[Ad] Endereço:Parasitology Division, CSIR-Central Drug Research Institute, Lucknow, India.
[Ti] Título:In vivo neutralization of α4 and ß7 integrins inhibits eosinophil trafficking and prevents lung injury during tropical pulmonary eosinophilia in mice.
[So] Source:Eur J Immunol;47(9):1501-1512, 2017 Sep.
[Is] ISSN:1521-4141
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Integrins regulate leukocyte trafficking during homeostasis and inflammatory conditions. However, the role of α4 and ß7 integrins in guiding eosinophil transmigration into the lungs during filarial manifestation of Tropical Pulmonary Eosinophilia (TPE) has not been explored. In this study, mice exhibiting TPE manifestations were administered with in vivo neutralizing antibodies against integrins α4 and ß7 or their combination and immuno-pathological parameters were evaluated. Results show an intact lung barrier, significantly lower lung inflammation and reduced eosinophil counts in the Bronchoalveolar lavage fluid and lungs of mice receiving anti-α4 ß7 treatment. Reduced eosinophil peroxidase and ß-hexosaminidase activity, downregulation of inflammatory genes, lower production of inflammatory lipid intermediates like prostaglandins E2 and D2, leukotriene B4 and cysteinyl leukotrienes were also noted in anti-α4 ß7 treated mice. Reduced accumulation of central memory, effector memory, regulatory T cells and lower production of IL-4, IL-5, and TGF-ß were other cardinal features of anti-α4 ß7 treated mice lungs. Flow cytometry-sorted lung eosinophils from anti-α4 ß7 treated mice showed higher apoptotic potential, downregulated anti-apoptotic gene Bcl-2, and exhibited reduced F-actin polymerization and calcium influx as compared to IgG controls. In summary, neutralization of α4 ß7 integrins impairs the transmigration, activation and survival of eosinophils and reduces TPE induced pathology in mice lungs.
[Mh] Termos MeSH primário: Anticorpos Neutralizantes/uso terapêutico
Brugia Malayi/imunologia
Filariose Linfática/terapia
Eosinófilos/imunologia
Imunoterapia/métodos
Lesão Pulmonar/prevenção & controle
Eosinofilia Pulmonar/terapia
[Mh] Termos MeSH secundário: Animais
Movimento Celular
Células Cultivadas
Citocinas/metabolismo
Filariose Linfática/imunologia
Seres Humanos
Mediadores da Inflamação/metabolismo
Integrina alfa4/imunologia
Cadeias beta de Integrinas/imunologia
Lesão Pulmonar/etiologia
Lesão Pulmonar/imunologia
Camundongos
Camundongos Endogâmicos
Proteínas Proto-Oncogênicas c-bcl-2/genética
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
Eosinofilia Pulmonar/complicações
Eosinofilia Pulmonar/imunologia
Linfócitos T Reguladores/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Cytokines); 0 (Inflammation Mediators); 0 (Integrin beta Chains); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (integrin beta7); 143198-26-9 (Integrin alpha4)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170725
[St] Status:MEDLINE
[do] DOI:10.1002/eji.201747086


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[PMID]:28728840
[Au] Autor:Lu TN; Ganganna B; Pham TT; Vo AV; Lu TP; Nguyen HT; Nguyen MT; Huynh PN; Truong NT; Lee J
[Ad] Endereço:College of Pharmacy, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon, Gangwon-do 24341, Republic of Korea; Department of Organic Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, 41 Dinh Tien Hoang Street, District 1, Ho Chi Minh City 701000, Viet N
[Ti] Título:Antitumor effect of the integrin α4 signaling inhibitor JK273 in non-small cell lung cancer NCI-H460 cells.
[So] Source:Biochem Biophys Res Commun;491(2):355-360, 2017 Sep 16.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lung cancer accounts for the highest death rate among cancers worldwide, with most patients being diagnosed with non-small cell lung cancer (NSCLC), urging more effective therapies. We report that JK273, a pyrrolo[2,3-d]pyrimidine analog, which inhibits α4 integrin signaling, showed a selective cytotoxic effect against HCI-H460 NSCLC cells, with an IC of 0.98 ± 0.15 µM, but showed less sensitivity to fibroblasts with a selectivity index (SI) greater than 30. This effect was attributed to cell cycle arrest at S phase by JK273 treatment, resulting in the apoptosis of NCI-H460 cells, further confirmed by exposing phosphatidylserine and morphological changes. Taken together with the previous study of JK273 inhibiting cell migration, we propose that JK273 could serve as an antitumor compound to specifically target cancer cells but not non-cancerous cells by triggering programmed cell death, in addition to anti-metastatic effects in cancer therapy.
[Mh] Termos MeSH primário: Compostos de Anilina/farmacologia
Antineoplásicos/farmacologia
Integrina alfa4/genética
Fase S/efeitos dos fármacos
Transdução de Sinais/efeitos dos fármacos
Tubercidina/análogos & derivados
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Expressão Gênica
Células HeLa
Células Hep G2
Seres Humanos
Concentração Inibidora 50
Integrina alfa4/metabolismo
Células Jurkat
Células MCF-7
Especificidade de Órgãos
Fosfatidilserinas
Mucosa Respiratória/efeitos dos fármacos
Mucosa Respiratória/metabolismo
Mucosa Respiratória/patologia
Transdução de Sinais/genética
Tubercidina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aniline Compounds); 0 (Antineoplastic Agents); 0 (JK 273); 0 (Phosphatidylserines); 143198-26-9 (Integrin alpha4); M351LCX45Y (Tubercidin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170824
[Lr] Data última revisão:
170824
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE


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[PMID]:28550073
[Au] Autor:Schneider C; Wunderlich G; Bleistein J; Fink GR; Deckert M; Brunn A; Lehmann HC
[Ad] Endereço:Department of Neurology, University of Cologne, Köln, Germany.
[Ti] Título:Lymphocyte antigens targetable by monoclonal antibodies in non-systemic vasculitic neuropathy.
[So] Source:J Neurol Neurosurg Psychiatry;88(9):756-760, 2017 Sep.
[Is] ISSN:1468-330X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To identify the most relevant antigens for monoclonal antibodies in lymphocytic infiltrates in non-systemic vasculitic neuropathy (NSVN). BACKGROUND: Current immunosuppressive treatment for NSVN is insufficient. Monoclonal antibodies might be a treatment option, but the expression profile for targetable antigens on lymphocytic infiltrates in NSVN is unknown. METHODS: Sural nerve biopsies from a cohort of patients with NSVN were immunohistochemically studied for the expression of potential candidate antigens in perivascular and intramural lymphocytic infiltrates and correlated with neurological and electrophysiological parameters. 20 patients with treatment naïve NSVN and 5 patients with idiopathic axonal neuropathy were included. RESULTS: The CD52, BAFF and CD49d antigens were expressed in epineurial, perivascular or intramural lymphocytes of all (20/20) patients. CD52 was most prominently expressed in 21.49% of all inflammatory infiltrates. BAFF and CD49d were detected in 11.25% and 10.99% of these lymphocytes, respectively. The CD20, CD25 and CD126 antigens were found less frequently and at low levels only (CD20: 10/20 patients, 5.84% of lymphocytes; CD25: 17/20 patients, 5.22% of lymphocytes; CD126: 3/20 patients, 0.15% of lymphocytes). CONCLUSION: This is the first study in NSVN that identifies antigens expressed by pathogenic lymphocytes, which are potential targets for future monoclonal antibody treatment. Our data suggest that NSVN is amenable to monoclonal antibodies and, moreover, that targeting CD52 may be particularly promising. Our results strongly warrant future clinical trials in NSVN with monoclonal antibodies.
[Mh] Termos MeSH primário: Anticorpos Monoclonais
Doenças do Sistema Nervoso Periférico/patologia
Nervo Sural/patologia
[Mh] Termos MeSH secundário: Idoso
Antígenos CD/análise
Antígenos de Neoplasias/análise
Fator Ativador de Células B/análise
Antígeno CD52
Glicoproteínas/análise
Seres Humanos
Inflamação/patologia
Integrina alfa4/análise
Meia-Idade
Estudos Retrospectivos
Vasculite/complicações
Vasculite/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antigens, CD); 0 (Antigens, Neoplasm); 0 (B-Cell Activating Factor); 0 (CD52 Antigen); 0 (CD52 protein, human); 0 (Glycoproteins); 0 (TNFSF13B protein, human); 143198-26-9 (Integrin alpha4)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170528
[St] Status:MEDLINE
[do] DOI:10.1136/jnnp-2017-315878


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[PMID]:28495929
[Au] Autor:Rothmeier AS; Marchese P; Langer F; Kamikubo Y; Schaffner F; Cantor J; Ginsberg MH; Ruggeri ZM; Ruf W
[Ad] Endereço:From the Department of Immunology and Microbiology (A.S.R., F.S., W.R.) and Molecular Medicine (P.M., Y.K., Z.M.R.), The Scripps Research Institute, La Jolla, CA; II. Medical Clinic and Polyclinic, University Medical Center Eppendorf, Hamburg, Germany (F.L.); Department of Medicine, University of Ca
[Ti] Título:Tissue Factor Prothrombotic Activity Is Regulated by Integrin-arf6 Trafficking.
[So] Source:Arterioscler Thromb Vasc Biol;37(7):1323-1331, 2017 Jul.
[Is] ISSN:1524-4636
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Coagulation initiation by tissue factor (TF) is regulated by cellular inhibitors, cell surface availability of procoagulant phosphatidylserine, and thiol-disulfide exchange. How these mechanisms contribute to keeping TF in a noncoagulant state and to generating prothrombotic TF remain incompletely understood. APPROACH AND RESULTS: Here, we study the activation of TF in primary macrophages by a combination of pharmacological, genetic, and biochemical approaches. We demonstrate that primed macrophages effectively control TF cell surface activity by receptor internalization. After cell injury, ATP signals through the purinergic receptor P2rx7 induce release of TF microvesicles. TF cell surface availability for release onto microvesicles is regulated by the GTPase arf6 associated with integrin α4ß1. Furthermore, microvesicles proteome analysis identifies activation of Gα as a participating factor in the release of microvesicles with prothrombotic activity in flowing blood. ATP not only prevents TF and phosphatidylserine internalization but also induces TF conversion to a conformation with high affinity for its ligand, coagulation factor VII. Although inhibition of dynamin-dependent internalization also exposes outer membrane procoagulant phosphatidylserine, the resulting TF microvesicles distinctly lack protein disulfide isomerase and high affinity TF and fail to produce fibrin strands typical for microvesicles generated by thrombo-inflammatory P2rx7 activation. CONCLUSIONS: These data show that procoagulant phospholipid exposure is not sufficient and that TF affinity maturation is required to generate prothrombotic microvesicles from a variety of cell types. These findings are significant for understanding TF-initiated thrombosis and should be considered in designing functional microvesicles-based diagnostic approaches.
[Mh] Termos MeSH primário: Fatores de Ribosilação do ADP/metabolismo
Coagulação Sanguínea
Integrina alfa4/metabolismo
Integrina alfa4beta1/metabolismo
Macrófagos/metabolismo
Tromboplastina/metabolismo
Trombose/metabolismo
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/metabolismo
Animais
Linhagem Celular Tumoral
Micropartículas Derivadas de Células/metabolismo
Fator VIIa/metabolismo
Técnicas de Introdução de Genes
Genótipo
Seres Humanos
Integrina alfa4/genética
Integrina alfa4beta1/genética
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Fenótipo
Fosfolipídeos/metabolismo
Transporte Proteico
Receptores Purinérgicos P2X7/metabolismo
Transdução de Sinais
Trombose/sangue
Trombose/genética
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Integrin alpha4beta1); 0 (P2RX7 protein, human); 0 (P2rx7 protein, mouse); 0 (Phospholipids); 0 (Receptors, Purinergic P2X7); 143198-26-9 (Integrin alpha4); 8L70Q75FXE (Adenosine Triphosphate); 9035-58-9 (Thromboplastin); EC 3.4.21.21 (Factor VIIa); EC 3.6.5.2 (ADP-Ribosylation Factors); EC 3.6.5.2 (ADP-ribosylation factor 6)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170513
[St] Status:MEDLINE
[do] DOI:10.1161/ATVBAHA.117.309315


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[PMID]:28414311
[Au] Autor:Chung KJ; Chatzigeorgiou A; Economopoulou M; Garcia-Martin R; Alexaki VI; Mitroulis I; Nati M; Gebler J; Ziemssen T; Goelz SE; Phieler J; Lim JH; Karalis KP; Papayannopoulou T; Blüher M; Hajishengallis G; Chavakis T
[Ad] Endereço:Department of Clinical Pathobiochemistry, Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
[Ti] Título:A self-sustained loop of inflammation-driven inhibition of beige adipogenesis in obesity.
[So] Source:Nat Immunol;18(6):654-664, 2017 Jun.
[Is] ISSN:1529-2916
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In obesity, inflammation of white adipose tissue (AT) is associated with diminished generation of beige adipocytes ('beige adipogenesis'), a thermogenic and energy-dissipating function mediated by beige adipocytes that express the uncoupling protein UCP1. Here we delineated an inflammation-driven inhibitory mechanism of beige adipogenesis in obesity that required direct adhesive interactions between macrophages and adipocytes mediated by the integrin α and its counter-receptor VCAM-1, respectively; expression of the latter was upregulated in obesity. This adhesive interaction reciprocally and concomitantly modulated inflammatory activation of macrophages and downregulation of UCP1 expression dependent on the kinase Erk in adipocytes. Genetic or pharmacological inactivation of the integrin α in mice resulted in elevated expression of UCP1 and beige adipogenesis of subcutaneous AT in obesity. Our findings, established in both mouse systems and human systems, reveal a self-sustained cycle of inflammation-driven impairment of beige adipogenesis in obesity.
[Mh] Termos MeSH primário: Adipócitos Bege
Adipogenia/imunologia
Tecido Adiposo Branco/imunologia
Diferenciação Celular/imunologia
Inflamação/imunologia
Macrófagos/imunologia
Obesidade/imunologia
[Mh] Termos MeSH secundário: Células 3T3-L1
Adipócitos/imunologia
Adipócitos/metabolismo
Adulto
Idoso
Idoso de 80 Anos ou mais
Animais
Adesão Celular/imunologia
Dieta Hiperlipídica
Regulação para Baixo
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Retroalimentação
Feminino
Técnicas de Silenciamento de Genes
Seres Humanos
Immunoblotting
Integrina alfa4/genética
Macrófagos/metabolismo
Masculino
Camundongos
Meia-Idade
Monócitos/imunologia
Obesidade/metabolismo
RNA Mensageiro/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Gordura Subcutânea
Linfócitos T/imunologia
Proteína Desacopladora 1/genética
Proteína Desacopladora 1/metabolismo
Molécula 1 de Adesão de Célula Vascular/genética
Molécula 1 de Adesão de Célula Vascular/metabolismo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Messenger); 0 (UCP1 protein, human); 0 (Ucp1 protein, mouse); 0 (Uncoupling Protein 1); 0 (Vascular Cell Adhesion Molecule-1); 143198-26-9 (Integrin alpha4); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171021
[Lr] Data última revisão:
171021
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170418
[St] Status:MEDLINE
[do] DOI:10.1038/ni.3728


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[PMID]:28386906
[Au] Autor:Strati P; Parikh SA; Chaffee KG; Achenbach SJ; Slager SL; Call TG; Ding W; Jelinek DF; Hanson CA; Kay NE; Shanafelt TD
[Ad] Endereço:Mayo Clinic College of Medicine, Rochester, MN, USA.
[Ti] Título:CD49d associates with nodal presentation and subsequent development of lymphadenopathy in patients with chronic lymphocytic leukaemia.
[So] Source:Br J Haematol;178(1):99-105, 2017 Jul.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:CD49d is a surface integrin that is expressed on chronic lymphocytic leukaemia (CLL) cells, and strongly correlates with more aggressive disease. Given its association with cell-cell adhesion and leucocyte trafficking, we hypothesized that patients with high CD49d expression would experience a clinical course dominated by lymphadenopathy. CD49d expression was measured by flow cytometry and considered positive if expressed by ≥30% of CLL cells. The study included 797 newly diagnosed CLL/small lymphocytic leukaemia patients; 279 (35%) were CD49d positive. CD49d-positive patients were more likely to present with lymphadenopathy (P < 0·001); a finding that persisted after adjusting for fluorescence in situ hybridisation (FISH) and IGHV mutation status [odds ratio (OR) 2·51; 95% confidence interval (CI) 1·64-3·83; P < 0·001]. Among CLL Rai 0 patients, CD49d positivity was associated with shorter time to development of lymphadenopathy (3·2 years vs not reached, P < 0·01). This association was maintained after adjusting for either FISH [hazard ratio (HR) 2·18; 95% CI 1·25-3·81; P = 0·006) or IGHV status (HR 2·02; 95% CI 1·11-3·69; P = 0·02) individually, but was attenuated when adjusting by both (HR 1·72; 95% CI 0·88-3·38; P = 0·11).These data demonstrate that CD49d-positive CLL patients experience a disease course dominated by lymphadenopathy. These findings could have implications for therapy selection and disease monitoring.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/sangue
Genes de Cadeia Pesada de Imunoglobulina/genética
Integrina alfa4/sangue
Leucemia Linfocítica Crônica de Células B/diagnóstico
Linfadenopatia/diagnóstico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Progressão da Doença
Feminino
Seguimentos
Seres Humanos
Região Variável de Imunoglobulina/genética
Leucemia Linfocítica Crônica de Células B/genética
Leucemia Linfocítica Crônica de Células B/patologia
Linfadenopatia/genética
Masculino
Meia-Idade
Mutação
Estadiamento de Neoplasias
Prognóstico
Fatores de Tempo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Immunoglobulin Variable Region); 143198-26-9 (Integrin alpha4)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170408
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.14647


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[PMID]:28167648
[Au] Autor:Shirani A; Stüve O
[Ad] Endereço:Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390; and.
[Ti] Título:Natalizumab for Multiple Sclerosis: A Case in Point for the Impact of Translational Neuroimmunology.
[So] Source:J Immunol;198(4):1381-1386, 2017 Feb 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Advances in translational neuroimmunology over the last two decades have revolutionized the treatment of relapsing forms of multiple sclerosis. A pathological hallmark of multiple sclerosis is the presence of leukocytes in the areas of disease activity in the CNS. Natalizumab inhibits the trafficking of lymphocytes from the blood into the brain and spinal cord by blocking the adhesion molecule α -integrin. Representing the enormous success of a molecular targeted approach, natalizumab was the first mAb approved for the treatment of relapsing-remitting multiple sclerosis. However, only a few months after its approval, natalizumab was withdrawn from the market because of an unanticipated life threatening adverse effect: progressive multifocal leukoencephalopathy. Natalizumab was later reintroduced with required adherence to a strict monitoring program. In this article, we review the bench-to-bedside journey of natalizumab, along with the lessons learned from postmarketing studies.
[Mh] Termos MeSH primário: Fatores Imunológicos/uso terapêutico
Esclerose Múltipla/tratamento farmacológico
Natalizumab/uso terapêutico
[Mh] Termos MeSH secundário: Ensaios Clínicos como Assunto
Seres Humanos
Fatores Imunológicos/efeitos adversos
Integrina alfa4/imunologia
Leucócitos/efeitos dos fármacos
Leucoencefalopatia Multifocal Progressiva
Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico
Esclerose Múltipla Recidivante-Remitente/imunologia
Natalizumab/efeitos adversos
Neuroimunomodulação/efeitos dos fármacos
Fatores de Risco
Pesquisa Médica Translacional
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Immunologic Factors); 0 (Natalizumab); 143198-26-9 (Integrin alpha4)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170208
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1601358


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[PMID]:28090055
[Au] Autor:Nakamura M; Itani K; Miyake K; Kunieda T; Kaneko S; Kusaka H
[Ad] Endereço:Department of Neurology, Kansai Medical University, Japan.
[Ti] Título:Natalizumab is Effective for the Treatment of Relapsing-remitting Tumefactive Multiple Sclerosis.
[So] Source:Intern Med;56(2):211-214, 2017.
[Is] ISSN:1349-7235
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:We herein report the case of a 57-year-old woman presenting with a biopsy-proven tumefactive demyelinating lesion as her first clinical event. Subsequently, she displayed a relapsing-remitting course with recurrence of large demyelinating lesions exceeding 2 cm in diameter rather than the small ovoid lesions characteristic of multiple sclerosis. Administration of interferon beta did not suppress the disease activity. Finally, treatment with natalizumab, which is a humanized monoclonal antibody against the cell-adhesion molecule α4-integrin, was initiated, resulting in clinical and radiological stabilization. Our experience here suggests that natalizumab may be an effective therapeutic option for relapsing-remitting tumefactive multiple sclerosis with high disease activity.
[Mh] Termos MeSH primário: Anticorpos Monoclonais Humanizados/uso terapêutico
Esclerose Múltipla Recidivante-Remitente/diagnóstico
Natalizumab/uso terapêutico
[Mh] Termos MeSH secundário: Anticorpos Monoclonais Humanizados/administração & dosagem
Diagnóstico Diferencial
Feminino
Seres Humanos
Integrina alfa4/imunologia
Imagem por Ressonância Magnética
Meia-Idade
Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem
Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico
Natalizumab/administração & dosagem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Humanized); 0 (Natalizumab); 143198-26-9 (Integrin alpha4)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170117
[St] Status:MEDLINE
[do] DOI:10.2169/internalmedicine.56.7588



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