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Pesquisa : A11.118.188 [Categoria DeCS]
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[PMID]:29350259
[Au] Autor:Zhu X; Zhang J; Wang Q; Fu H; Chang Y; Kong Y; Lv M; Xu L; Liu K; Huang X; Zhang X
[Ad] Endereço:Peking University People's Hospital, Peking University Institute of Hematology, Beijing, 100044, China.
[Ti] Título:Diminished expression of ß2-GPI is associated with a reduced ability to mitigate complement activation in anti-GPIIb/IIIa-mediated immune thrombocytopenia.
[So] Source:Ann Hematol;97(4):641-654, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Anti-GPIIb/IIIa-mediated complement activation has been reported to be important in the pathogenesis of immune thrombocytopenia (ITP). However, the role of the complement system and the involved regulatory mechanism remain equivocal. Beta2-glycoprotein I (ß2-GPI), known as the main target for antiphospholipid autoantibodies, has been demonstrated as a complement regulator. Here, we investigated the complement-regulatory role of ß2-GPI in anti-GPIIb/IIIa-mediated ITP. Plasma complement activation and enhanced complement activation capacity (CAC) were found in ITP patients with anti-GPIIb/IIIa antibodies in vivo and in vitro. Diminished plasma levels of ß2-GPI were shown in patients of this group, which was inversely correlated with C5b-9 deposition. C5b-9 generation was inhibited by approximate physiological concentrations of ß2-GPI, in a dose-dependent manner. Inhibition of C3a generation by ß2-GPI and the existence of ß2-GPI/C3 complexes in plasma indicated a regulation on the level of the C3 convertase. Furthermore, ß2-GPI down-regulated the phosphorylation levels of c-Jun N-terminal kinase (JNK) and cleavage of BH3 interacting domain death agonist (Bid) and ultimately harbored platelet lysis. Our findings may provide a novel link between diminished plasma levels of ß2-GPI and enhanced complement activation, indicating ß2-GPI as a potential diagnostic biomarker and therapeutic target in the treatment of anti-GPIIb/IIIa-mediated ITP.
[Mh] Termos MeSH primário: Ativação do Complemento
Regulação para Baixo
Isoanticorpos/metabolismo
Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores
Púrpura Trombocitopênica Idiopática/metabolismo
beta 2-Glicoproteína I/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Biomarcadores/sangue
Plaquetas/imunologia
Plaquetas/metabolismo
Plaquetas/patologia
China/epidemiologia
Convertases de Complemento C3-C5/metabolismo
Complemento C3a/metabolismo
Feminino
Seres Humanos
Masculino
Meia-Idade
Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo
Complexo Glicoproteico GPIb-IX de Plaquetas/antagonistas & inibidores
Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo
Púrpura Trombocitopênica Idiopática/imunologia
Púrpura Trombocitopênica Idiopática/patologia
Púrpura Trombocitopênica Idiopática/fisiopatologia
Risco
Trombocitopenia/sangue
Trombocitopenia/imunologia
Trombocitopenia/metabolismo
Trombose/epidemiologia
Trombose/etiologia
Adulto Jovem
beta 2-Glicoproteína I/sangue
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Isoantibodies); 0 (Platelet Glycoprotein GPIIb-IIIa Complex); 0 (Platelet Glycoprotein GPIb-IX Complex); 0 (beta 2-Glycoprotein I); 0 (glycoprotein receptor GPIb-IX); 80295-42-7 (Complement C3a); EC 3.4.21.- (Complement C3-C5 Convertases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180120
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-017-3215-3


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[PMID]:29332224
[Au] Autor:Tong D; Yu M; Guo L; Li T; Li J; Novakovic VA; Dong Z; Tian Y; Kou J; Bi Y; Wang J; Zhou J; Shi J
[Ad] Endereço:Department of Hematology, First Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China.
[Ti] Título:Phosphatidylserine-exposing blood and endothelial cells contribute to the hypercoagulable state in essential thrombocythemia patients.
[So] Source:Ann Hematol;97(4):605-616, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The mechanisms of thrombogenicity in essential thrombocythemia (ET) are complex and not well defined. Our objective was to explore whether phosphatidylserine (PS) exposure on blood cells and endothelial cells (ECs) can account for the increased thrombosis and distinct thrombotic risks among mutational subtypes in ET. Using flow cytometry and confocal microscopy, we found that the levels of PS-exposing erythrocytes, platelets, leukocytes, and serum-cultured ECs were significantly higher in each ET group [JAK2, CALR, and triple-negative (TN) (all P < 0.001)] than those in controls. Among ET patients, those with JAK2 mutations showed higher levels of PS-positive erythrocytes, platelets, neutrophils, and serum-cultured ECs than TN patients or those with CALR mutations, which show similar levels. Coagulation function assays showed that higher levels of PS-positive blood cells and serum-cultured ECs led to markedly shortened coagulation time and dramatically increased levels of FXa, thrombin, and fibrin production. This procoagulant activity could be largely blocked by addition of lactadherin (approx. 70% inhibition). Confocal microscopy showed that the FVa/FXa complex and fibrin fibrils colocalized with PS on ET serum-cultured ECs. Additionally, we found a relationship between D-dimer, prothrombin fragment F1 + 2, and PS exposure. Our study reveals a previously unrecognized link between hypercoagulability and exposed PS on cells, which might also be associated with distinct thrombotic risks among mutational subtypes in ET. Thus, blocking PS-binding sites may represent a new therapeutic target for preventing thrombosis in ET.
[Mh] Termos MeSH primário: Plaquetas/patologia
Endotélio Vascular/patologia
Eritrócitos/patologia
Leucócitos/patologia
Fosfatidilserinas/metabolismo
Trombocitemia Essencial/fisiopatologia
Trombose/etiologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Substituição de Aminoácidos
Plaquetas/metabolismo
Calreticulina/genética
Calreticulina/metabolismo
Células Cultivadas
China/epidemiologia
Endotélio Vascular/metabolismo
Eritrócitos/metabolismo
Feminino
Células Endoteliais da Veia Umbilical Humana/citologia
Células Endoteliais da Veia Umbilical Humana/metabolismo
Seres Humanos
Janus Quinase 2/genética
Janus Quinase 2/metabolismo
Leucócitos/metabolismo
Masculino
Meia-Idade
Mutação
Receptores de Trombopoetina/genética
Receptores de Trombopoetina/metabolismo
Risco
Propriedades de Superfície
Trombocitemia Essencial/genética
Trombocitemia Essencial/metabolismo
Trombocitemia Essencial/patologia
Trombose/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calreticulin); 0 (Phosphatidylserines); 0 (Receptors, Thrombopoietin); 0 (calreticulin, human); 143641-95-6 (MPL protein, human); EC 2.7.10.2 (JAK2 protein, human); EC 2.7.10.2 (Janus Kinase 2)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180115
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-018-3228-6


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[PMID]:28470446
[Au] Autor:Sundaran PS; Bhaskaran A; Alex ST; Prasad T; Haritha VH; Anie Y; Kumary TV; Anil Kumar PR
[Ad] Endereço:Division of Tissue Culture, Department of Applied Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, 695 012, India.
[Ti] Título:Drug loaded microbeads entrapped electrospun mat for wound dressing application.
[So] Source:J Mater Sci Mater Med;28(6):88, 2017 Jun.
[Is] ISSN:1573-4838
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A new design of antibiotic loaded wound dressing and its initial in vitro evaluation is described. Chitosan microbeads loaded with ampicillin were sandwiched within polycaprolactone electrospun mat (MbAPPCL). The morphology was analyzed by scanning electron microscopy and surface chemistry was characterized by Fourier Transform Infrared Spectroscopy. In vitro cytotoxicity using L-929 fibroblast cells by direct contact test and elution assay revealed non-cytotoxic nature of MbAPPCL. The cell adhesion and viability analysis further confirmed the cytocompatibility of MbAPPCL as a wound dressing material. Percentage hemolysis and platelet adhesion on the mat exposed to blood substantiated the hemocompatibility. The antibiotic susceptibility test analyzed on Staphylococcus aureus by agar plate method confirmed the drug release and antimicrobial property. The proposed wound dressing model explained with ampicillin as a candidate drug has the potential to include microbeads with different antibiotics for multi drug treatment.
[Mh] Termos MeSH primário: Bandagens
Portadores de Fármacos
Microesferas
[Mh] Termos MeSH secundário: Animais
Antibacterianos/química
Antibacterianos/farmacologia
Materiais Biocompatíveis
Plaquetas
Linhagem Celular
Quitosana
Técnicas Eletroquímicas
Fibroblastos/fisiologia
Teste de Materiais
Camundongos
Penicilinas/química
Penicilinas/farmacologia
Staphylococcus aureus/efeitos dos fármacos
Estreptomicina/química
Estreptomicina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Biocompatible Materials); 0 (Drug Carriers); 0 (Penicillins); 9012-76-4 (Chitosan); Y45QSO73OB (Streptomycin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1007/s10856-017-5893-8


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[PMID]:27775924
[Au] Autor:Im SH; Jung Y; Jang Y; Kim SH
[Ad] Endereço:KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Korea. Biomaterials Research Center, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
[Ti] Título:Poly(L-lactic acid) scaffold with oriented micro-valley surface and superior properties fabricated by solid-state drawing for blood-contact biomaterials.
[So] Source:Biofabrication;8(4):045010, 2016 10 24.
[Is] ISSN:1758-5090
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Most biomaterials composed of biodegradable polymers will contact either accidentally or consistently with blood and this commonly requires both good  mechanical strength and blood compatibility. Despite this demand, current processing methods still make it difficult and complex to simultaneously improve the two properties. To overcome present limitations, the aim of this work is to develop a solid-state drawing which is a novel method for blood-contact biomaterials that can simultaneously improve the two essential factors of mechanical strength and blood compatibility, as well as induce a micro-patterned surface. Solid-state drawn (SSD) poly(L-lactic acid) (PLLA) film significantly maximally increased tensile strength and elastic modulus about ninefold and sixfold, respectively, compared to undrawn film. Furthermore, it was determined that SSD-PLLA film had highly developed molecular orientation, higher crystallinity and surface hydrophobicity. Additionally, the SSD method could greatly reduce roughness of the surface and induce the formation of aligned valleys, forming microstructures on the film surface. The topographical cue delayed hydrolytic degradation and prevented damage on the surface by NaOH of alkali compounds are compared with undrawn film. In energy-dispersive x-ray spectroscopy analysis, the surface of SSD film treated by NaOH was not detected on any ions whereas undrawn film held foreign ions on surface defects. The hemolysis rate of SSD film was considerably decreased with an increase of draw ratio up to 0.2% maximally and SSD film has shown greatly lower platelet adhesion compared to undrawn film in blood-compatibility analysis. Interestingly, one-directional alignment of micro-valley structure on SSD film could promote initial adhesion of human umbilical vein endothelial cells (HUVEC) compared with undrawn film and guide the direction of HUVEC. In conclusion, the newly designed SSD method has shown potential for developing blood-contact biomaterials simply due to great mechanical properties, blood compatibility and an aligned micro-patterned surface.
[Mh] Termos MeSH primário: Materiais Biocompatíveis/química
Poliésteres/química
[Mh] Termos MeSH secundário: Materiais Biocompatíveis/farmacologia
Plaquetas/citologia
Varredura Diferencial de Calorimetria
Adesão Celular/efeitos dos fármacos
Módulo de Elasticidade
Eritrócitos/citologia
Eritrócitos/efeitos dos fármacos
Hemólise/efeitos dos fármacos
Células Endoteliais da Veia Umbilical Humana
Seres Humanos
Microscopia de Força Atômica
Espectrometria por Raios X
Propriedades de Superfície
Resistência à Tração
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biocompatible Materials); 0 (Polyesters); 459TN2L5F5 (poly(lactide))
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


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[PMID]:28460641
[Au] Autor:Bernardi M; Agostini F; Chieregato K; Amati E; Durante C; Rassu M; Ruggeri M; Sella S; Lombardi E; Mazzucato M; Astori G
[Ad] Endereço:Advanced Cellular Therapy Laboratory, Hematology Unit, Vicenza Hospital, Vicenza, Italy.
[Ti] Título:The production method affects the efficacy of platelet derivatives to expand mesenchymal stromal cells in vitro.
[So] Source:J Transl Med;15(1):90, 2017 May 01.
[Is] ISSN:1479-5876
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The use of fetal bovine serum (FBS) as a media supplement for the ex vivo expansion of bone-marrow derived mesenchymal stromal cells (BM-MSC) has been discouraged by regulatory agencies, due to the risk of transmitting zoonoses and to elicit immune reactions in the host once transplanted. Platelet derivatives are valid FBS substitutes due to their content of growth factors that can be released disrupting the platelets by physical methods or physiological stimuli. We compared platelet derivatives produced by freezing/thawing (platelet lysates, PL) or after CaCl activation (platelet releasate surnatant rich in growth factors, PR-SRGF) for their content in growth factors and their ability to support the ex vivo expansion of BM-MSC. METHODS: The cytokine content in the two platelet derivatives was evaluated. BM-MSC were expanded in complete medium containing 10, 7.5 and 5% PL or PR-SRGF and the cell phenotype, clonogenic capacity, immunomodulation properties and tri-lineage differentiation potential of the expanded cells in both media were investigated. RESULTS: The concentration of PDGF-AB, PDGF-AA, PDGF-BB in PR-SRGF resulted to be respectively 5.7×, 1.7× and 2.3× higher compared to PL. PR-SRGF promoted a higher BM-MSC proliferation rate compared to PL not altering BM-MSC phenotype. Colony forming efficiency of BM-MSC expanded in PR-SRGF showed a frequency of colonies significantly higher than cells expanded in PL. BM-MSC expanded in PL or PR-SRGF maintained their immunomodulatory properties against activated lymphocytes even if BM-MSC expanded in FBS performed significantly better. CONCLUSIONS: The method used to release platelet factors significantly affects the enrichment in growth factors and overall product performance. The standardization of the production process of platelet derivatives and the definition of their release criteria requires further investigation.
[Mh] Termos MeSH primário: Plaquetas/metabolismo
Técnicas de Cultura de Células/métodos
Células Mesenquimais Estromais/citologia
[Mh] Termos MeSH secundário: Diferenciação Celular
Linhagem da Célula
Proliferação Celular
Ensaio de Unidades Formadoras de Colônias
Seres Humanos
Imunomodulação
Imunofenotipagem
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Intercellular Signaling Peptides and Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1186/s12967-017-1185-9


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[PMID]:28470742
[Au] Autor:Lee DD; Muskaj I; Savage W
[Ad] Endereço:Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
[Ti] Título:Platelet proteins cause basophil histamine release through an immunoglobulin-dependent mechanism.
[So] Source:Transfusion;57(7):1709-1716, 2017 07.
[Is] ISSN:1537-2995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: A general understanding of allergic transfusion reaction mechanisms remains elusive. Multiple mechanisms have been proposed, but none have been compared experimentally. STUDY DESIGN AND METHODS: We used histamine release (HR) from healthy human donor basophils to model allergic transfusion reactions. Platelet component supernatant (plasma), platelet lysate, and manipulated platelet lysates (dialyzed, delipidated, trypsinized, mild heat-inactivated, and ultracentrifuged) were used to characterize allergic stimuli. Immunoglobulin-dependent mechanisms were investigated through cell surface immunoglobulin depletion and ibrutinib signaling inhibition. HR induced by platelet mitochondria was compared with HR by platelet lysate with or without DNase treatment. RESULTS: Robust, dose-responsive HR to platelet lysate was observed in two of eight nulliparous, never-transfused, healthy donors. No HR was observed with plasma. Among manipulated platelet lysates, only trypsin treatment significantly reduced HR (39% reduction; p = 0.008). HR in response to platelet lysate significantly decreased with either cell surface immunoglobulin depletion or ibrutinib pretreatment. Platelet mitochondria induced minimal basophil HR, and DNase treatment did not inhibit platelet lysate-induced HR. CONCLUSION: Type I immediate hypersensitivity to platelet proteins may be an allergic transfusion reaction mechanism. Prior sensitization to human proteins is not required for basophil responses to platelet proteins. Further study into the relative contributions of hypersensitivity to platelet versus plasma proteins in transfusion is warranted.
[Mh] Termos MeSH primário: Basófilos/fisiologia
Plaquetas/imunologia
Proteínas Sanguíneas/imunologia
Liberação de Histamina
Hipersensibilidade Imediata/etiologia
Imunoglobulina E/imunologia
Reação Transfusional/etiologia
[Mh] Termos MeSH secundário: Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Blood Proteins); 37341-29-0 (Immunoglobulin E)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1111/trf.14126


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[PMID]:29207378
[Au] Autor:Akkiz H; Carr BI; Yalçin K K; Guerra V; Kuran S; Altintas E; Üsküdar O; Karaogullarindan Ü; Özakyol A; Tokmak S; Yücesoy M; Bahçeci HI; Ülkü A; Akçam T; Yalçin Polat K; Ekinci N; Simsek H; Örmeci N; Sonsuz A; Demir M; Kiliç M; Uygun A; Balli T; Demir A; Arslan B; Doran F
[Ad] Endereço:Gastroenterology Department, Çukurova Üniversitesi, Adana, Turkey.
[Ti] Título:Characteristics of Hepatocellular Carcinoma Aggressiveness Factors in Turkish Patients.
[So] Source:Oncology;94(2):116-124, 2018.
[Is] ISSN:1423-0232
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:A large cohort of hepatocellular carcinoma (HCC) patients from several collaborating Turkish institutions were examined for the tumor parameters of maximum diameter (MTD), portal vein thrombosis (PVT), and α-fetoprotein (AFP) levels. A relationship was found between MTD and blood platelet levels. Patients with large ≥5 cm tumors who had normal platelet levels had significantly larger tumors, higher percent of PVT, and significantly lower blood total bilirubin and liver cirrhosis than similar ≥5 cm tumor patients having thrombocytopenia. A comparison of patients with and without PVT showed significantly larger tumors, greater multifocality, blood AFP, and C-reactive protein levels, and, interestingly, lower HDL levels in the patients with PVT. Fifty-eight percent of the total cohort had AFP levels ≤100 IU/mL (and 42.1% had values ≤20 IU/mL). These patients had significantly smaller tumors, less tumor multifocality and percent PVT, lower total bilirubin, and less cirrhosis. There was considerable geographic heterogeneity within Turkey in the patterns of HCC presentation, with areas of higher and lower hepatitis B virus, hepatitis D virus, cirrhosis, and tumor aggressiveness parameters. Turkish patients thus have distinct patterns of presentation, but the biological relationships between MTD and both platelets and bilirubin levels are similar to the relationships that have been reported in other ethnic patient groups.
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/patologia
Neoplasias Hepáticas/patologia
[Mh] Termos MeSH secundário: Bilirrubina/sangue
Biomarcadores Tumorais/sangue
Plaquetas/patologia
Proteína C-Reativa/metabolismo
Carcinoma Hepatocelular/sangue
Carcinoma Hepatocelular/metabolismo
Feminino
Seres Humanos
Cirrose Hepática/sangue
Cirrose Hepática/metabolismo
Cirrose Hepática/patologia
Testes de Função Hepática/métodos
Neoplasias Hepáticas/sangue
Neoplasias Hepáticas/metabolismo
Masculino
Meia-Idade
Veia Porta/patologia
Prognóstico
Estudos Prospectivos
Trombocitopenia/sangue
Trombocitopenia/metabolismo
Trombocitopenia/patologia
Turquia
Trombose Venosa/sangue
Trombose Venosa/metabolismo
Trombose Venosa/patologia
alfa-Fetoproteínas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (alpha-Fetoproteins); 9007-41-4 (C-Reactive Protein); RFM9X3LJ49 (Bilirubin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE
[do] DOI:10.1159/000484564


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[PMID]:28467294
[Au] Autor:van der Pol E; Harrison P
[Ad] Endereço:a Biomedical Engineering & Physics , Academic Medical Centre, University of Amsterdam , Amsterdam , The Netherlands.
[Ti] Título:From platelet dust to gold dust: physiological importance and detection of platelet microvesicles.
[So] Source:Platelets;28(3):211-213, 2017 05.
[Is] ISSN:1369-1635
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Plaquetas/química
Micropartículas Derivadas de Células/metabolismo
Integrina beta3/genética
Trombose/fisiopatologia
[Mh] Termos MeSH secundário: Transporte Biológico/fisiologia
Biomarcadores/metabolismo
Plaquetas/ultraestrutura
Comunicação Celular/fisiologia
Micropartículas Derivadas de Células/genética
Micropartículas Derivadas de Células/ultraestrutura
Expressão Gênica
Ouro/química
Seres Humanos
Imuno-Histoquímica
Integrina beta3/metabolismo
Nanopartículas Metálicas/química
Tamanho da Partícula
Ativação Plaquetária/fisiologia
Trombose/genética
Trombose/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Biomarkers); 0 (ITGB3 protein, human); 0 (Integrin beta3); 7440-57-5 (Gold)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1080/09537104.2017.1282781


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[PMID]:28453956
[Au] Autor:Ta HT; Li Z; Hagemeyer CE; Cowin G; Zhang S; Palasubramaniam J; Alt K; Wang X; Peter K; Whittaker AK
[Ad] Endereço:Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australia. Electronic address: h.ta@uq.edu.au.
[Ti] Título:Molecular imaging of activated platelets via antibody-targeted ultra-small iron oxide nanoparticles displaying unique dual MRI contrast.
[So] Source:Biomaterials;134:31-42, 2017 Jul.
[Is] ISSN:1878-5905
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Magnetic resonance imaging (MRI) is a powerful and indispensable tool in medical research, clinical diagnosis, and patient care due to its high spatial resolution and non-limited penetration depth. The simultaneous use of positive and negative MRI imaging that employs the same contrast agents will significantly improve detection accuracy. Here we report the development of functional multimodal iron oxide nanoparticles for targeted MRI of atherothrombosis using a combination of chemical and biological conjugation techniques. Monodisperse, water-soluble and biocompatible ultra-small magnetic dual contrast iron oxide nanoparticles (DCIONs) were generated using a high-temperature co-precipitation route and appeared to be efficient positive and negative dual contrast agents for magnetic resonance imaging. Using a unique chemo-enzymatic approach involving copper-free click chemistry and Staphylococcus aureus sortase A enzyme conjugation, DCIONs were functionalized with single-chain antibodies (scFv) directed against activated platelets for targeting purposes. The DCIONs were also labelled with fluorescent molecules to allow for optical imaging. The antigen binding activity of the scFv was retained and resulted in the successful targeting of contrast agents to thrombosis as demonstrated in a range of in vitro and in vivo experiments. T - and T -weighted MRI of thrombi was recorded and demonstrated the great potential of dual T /T contrast iron oxide particles in imaging of cardiovascular disease.
[Mh] Termos MeSH primário: Plaquetas/fisiologia
Meios de Contraste/química
Compostos Férricos/química
Imagem por Ressonância Magnética/métodos
Nanopartículas de Magnetita/química
Patologia Molecular/métodos
[Mh] Termos MeSH secundário: Animais
Células CHO
Cricetulus
Citometria de Fluxo
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Contrast Media); 0 (Ferric Compounds); 0 (Magnetite Nanoparticles); 1K09F3G675 (ferric oxide)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:28455282
[Au] Autor:Sim X; Jarocha D; Hayes V; Hanby HA; Marks MS; Camire RM; French DL; Poncz M; Gadue P
[Ad] Endereço:Department of Cell and Molecular Biology, University of Pennsylvania School of Medicine, Philadelphia, PA.
[Ti] Título:Identifying and enriching platelet-producing human stem cell-derived megakaryocytes using factor V uptake.
[So] Source:Blood;130(2):192-204, 2017 07 13.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Stem cell-derived platelets have the potential to replace donor platelets for transfusion. Defining the platelet-producing megakaryocytes (MKs) within the heterogeneous MK culture may help to optimize the in vitro generation of platelets. Using 2 human stem cell models of megakaryopoiesis, we identified novel MK populations corresponding to distinct maturation stages. An immature, low granular (LG) MK pool (defined by side scatter on flow cytometry) gives rise to a mature high granular (HG) pool, which then becomes damaged by apoptosis and glycoprotein Ib α chain (CD42b) shedding. We define an undamaged HG/CD42b MK subpopulation, which endocytoses fluorescently labeled coagulation factor V (FV) from the media into α-granules and releases functional FV CD42b human platelet-like particles in vitro and when infused into immunodeficient mice. Importantly, these FV particles have the same size distribution as infused human donor platelets and are preferentially incorporated into clots after laser injury. Using drugs to protect HG MKs from apoptosis and CD42b shedding, we also demonstrate that apoptosis precedes CD42b shedding and that apoptosis inhibition enriches the FV HG/CD42b MKs, leading to increased platelet yield in vivo, but not in vitro. These studies identify a transition between distinct MK populations in vitro, including one that is primed for platelet release. Technologies to optimize and select these platelet-ready MKs may be important to efficiently generate functional platelets from in vitro-grown MKs.
[Mh] Termos MeSH primário: Plaquetas/citologia
Células da Medula Óssea/imunologia
Fator V/genética
Células Progenitoras de Megacariócitos/citologia
Megacariócitos/citologia
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Arteríolas/efeitos dos fármacos
Arteríolas/imunologia
Arteríolas/lesões
Biomarcadores/sangue
Plaquetas/imunologia
Células da Medula Óssea/citologia
Células da Medula Óssea/efeitos dos fármacos
Diferenciação Celular
Linhagem da Célula/imunologia
Endocitose
Fator V/imunologia
Fator V/farmacologia
Citometria de Fluxo
Expressão Gênica
Seres Humanos
Imunofenotipagem
Lasers
Células Progenitoras de Megacariócitos/imunologia
Megacariócitos/imunologia
Camundongos
Camundongos SCID
Complexo Glicoproteico GPIb-IX de Plaquetas/genética
Complexo Glicoproteico GPIb-IX de Plaquetas/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Biomarkers); 0 (Platelet Glycoprotein GPIb-IX Complex); 9001-24-5 (Factor V)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2017-01-761049



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