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[PMID]:27770464
[Au] Autor:Raschke M; Igl BW; Kenny J; Collins J; Dertinger SD; Labash C; Bhalli JA; Tebbe CC; McNeil KM; Sutter A
[Ad] Endereço:Bayer Pharma AG, Muellerstrasse 178, Berlin, 13353, Germany.
[Ti] Título:In Vivo Pig-a gene mutation assay: Guidance for 3Rs-friendly implementation.
[So] Source:Environ Mol Mutagen;57(9):678-686, 2016 Dec.
[Is] ISSN:1098-2280
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The rodent Pig-a assay is an in vivo method for the detection of gene mutation, where lack of glycosylphosphatidylinositol-anchored proteins on the surface of circulating red blood cells (RBCs) serves as a reporter for Pig-a gene mutation. In the case of rats, the frequency of mutant phenotype RBCs is measured via fluorescent anti-CD59 antibodies and flow cytometry. The Pig-a assay meets the growing expectations for novel approaches in animal experimentation not only focusing on the scientific value of the assay but also on animal welfare aspects (3Rs principles), for example, amenable to integration into pivotal rodent 28-day general toxicology studies. However, as recommended in the Organisation for Economic Co-operation and Development Test Guidelines for genotoxicity testing, laboratories are expected to demonstrate their proficiency. While this has historically involved the extensive use of animals, here we describe an alternative approach based on a series of blood dilutions covering a range of mutant frequencies. The experiments described herein utilized either non-fluorescent anti-CD59 antibodies to provide elevated numbers of mutant-like cells, or a low volume blood sample from a single N-ethyl-N-nitrosourea treated animal. Results from these so-called reconstruction experiments from four independent laboratories showed good overall precision (correlation coefficients: 0.9979-0.9999) and accuracy (estimated slope: 0.71-1.09) of mutant cell scoring, which was further confirmed by Bland-Altman analysis. These data strongly support the use of reconstruction experiments for training purposes and demonstrating laboratory proficiency with very few animals, an ideal situation given the typically conflicting goals of demonstrating laboratory proficiency and reducing the use of animals. Environ. Mol. Mutagen. 57:678-686, 2016. © 2016 Wiley Periodicals, Inc.
[Mh] Termos MeSH primário: Alternativas ao Uso de Animais
Etilnitrosoureia/toxicidade
Proteínas de Membrana/genética
Testes de Mutagenicidade/métodos
Mutagênicos/toxicidade
Mutação
[Mh] Termos MeSH secundário: Bem-Estar do Animal
Animais
Antígenos CD59/análise
Eritrócitos/efeitos de drogas
Eritrócitos/metabolismo
Citometria de Fluxo
Guias como Assunto
Laboratórios/normas
Masculino
Ratos Endogâmicos
Reticulócitos/efeitos de drogas
Reticulócitos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD59); 0 (Membrane Proteins); 0 (Mutagens); 0 (phosphatidylinositol glycan-class A protein); P8M1T4190R (Ethylnitrosourea)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170609
[Lr] Data última revisão:
170609
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161022
[St] Status:MEDLINE
[do] DOI:10.1002/em.22060


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[PMID]:28330937
[Au] Autor:Kinoshita M; Suzuki KG; Matsumori N; Takada M; Ano H; Morigaki K; Abe M; Makino A; Kobayashi T; Hirosawa KM; Fujiwara TK; Kusumi A; Murata M
[Ad] Endereço:Lipid Active Structure Project, Exploratory Research for Advanced Technology Organization, Japan Science and Technology Agency, Osaka University, Osaka 560-0043, Japan.
[Ti] Título:Raft-based sphingomyelin interactions revealed by new fluorescent sphingomyelin analogs.
[So] Source:J Cell Biol;216(4):1183-1204, 2017 Apr 03.
[Is] ISSN:1540-8140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sphingomyelin (SM) has been proposed to form cholesterol-dependent raft domains and sphingolipid domains in the plasma membrane (PM). How SM contributes to the formation and function of these domains remains unknown, primarily because of the scarcity of suitable fluorescent SM analogs. We developed new fluorescent SM analogs by conjugating a hydrophilic fluorophore to the SM choline headgroup without eliminating its positive charge, via a hydrophilic nonaethylene glycol linker. The new analogs behaved similarly to the native SM in terms of their partitioning behaviors in artificial liquid order-disorder phase-separated membranes and detergent-resistant PM preparations. Single fluorescent molecule tracking in the live-cell PM revealed that they indirectly interact with each other in cholesterol- and sphingosine backbone-dependent manners, and that, for ∼10-50 ms, they undergo transient colocalization-codiffusion with a glycosylphosphatidylinositol (GPI)-anchored protein, CD59 (in monomers, transient-dimer rafts, and clusters), in CD59-oligomer size-, cholesterol-, and GPI anchoring-dependent manners. These results suggest that SM continually and rapidly exchanges between CD59-associated raft domains and the bulk PM.
[Mh] Termos MeSH primário: Corantes Fluorescentes/metabolismo
Esfingomielinas/metabolismo
[Mh] Termos MeSH secundário: Animais
Antígenos CD59/metabolismo
Células CHO
Linhagem Celular
Membrana Celular/metabolismo
Colesterol/metabolismo
Cricetulus
Detergentes/metabolismo
Glicosilfosfatidilinositóis/metabolismo
Interações Hidrofóbicas e Hidrofílicas
Microdomínios da Membrana/metabolismo
Esfingolipídeos/metabolismo
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD59); 0 (Detergents); 0 (Fluorescent Dyes); 0 (Glycosylphosphatidylinositols); 0 (Sphingolipids); 0 (Sphingomyelins); 101754-01-2 (CD59 protein, human); 97C5T2UQ7J (Cholesterol)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170531
[Lr] Data última revisão:
170531
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170323
[St] Status:MEDLINE
[do] DOI:10.1083/jcb.201607086


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[PMID]:28347253
[Au] Autor:Yang P; Li B; Yin QF; Wang YJ
[Ad] Endereço:Department of Biology, Medical College of Qingdao University, Qingdao, People's Republic of China.
[Ti] Título:Carboxymethyl chitosan nanoparticles coupled with CD59-specific ligand peptide for targeted delivery of C-phycocyanin to HeLa cells.
[So] Source:Tumour Biol;39(3):1010428317692267, 2017 Mar.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The combination of nanotechnology and medicine will be the next generation of vehicles for targeted drug delivery. Carboxymethyl chitosan loaded with the anticancer drug C-phycocyanin and the CD59-specific ligand peptide for cancer cell targeting were used to create C-phycocyanin/carboxymethyl chitosan-CD59-specific ligand peptide nanoparticles using the ionic-gelation method. Optimal synthesis conditions, selected by response surface methodology, comprised the ratio carboxymethyl chitosan:C-phycocyanin = 3:1, and carboxymethyl chitosan and CaCl concentrations of 2.0 and 1.0 mg/mL, respectively. The resulting nanoparticles were spherical, with diameters of approximately 200 nm; the entrapment efficient was about 65%; and the drug loading was about 20%. The release of C-phycocyanin from C-phycocyanin/carboxymethyl chitosan nanoparticles was pH sensitive and had a sustainable effect in vitro. Guided by the CD59-specific ligand peptide, the nanoparticles efficiently targeted the surface of HeLa cells and had an obvious inhibitory effect on HeLa cell proliferation as determined by methyl thiazolyl tetrazolium assays. The nanoparticles were hemocompatible and induced apoptosis by upregulation of cleaved caspase-3 and cleaved polyADP-ribose polymerase proteins, and downregulation of Bcl-2 proteins. Our study provides a novel approach to the research and development of marine drugs, and support for targeted therapy using anticancer drugs.
[Mh] Termos MeSH primário: Quitosana/análogos & derivados
Nanopartículas/administração & dosagem
Peptídeos/administração & dosagem
Ficocianina/administração & dosagem
[Mh] Termos MeSH secundário: Antígenos CD59/imunologia
Caspase 3/biossíntese
Quitosana/administração & dosagem
Quitosana/química
Sistemas de Liberação de Medicamentos
Liberação Controlada de Fármacos
Epitopos
Células HeLa
Humanos
Nanopartículas/química
Peptídeos/química
Peptídeos/imunologia
Ficocianina/química
Proteínas Proto-Oncogênicas c-bcl-2/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD59); 0 (Epitopes); 0 (Peptides); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (carboxymethyl-chitosan); 101754-01-2 (CD59 protein, human); 11016-15-2 (Phycocyanin); 9012-76-4 (Chitosan); EC 3.4.22.- (Caspase 3)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170407
[Lr] Data última revisão:
170407
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170328
[St] Status:MEDLINE
[do] DOI:10.1177/1010428317692267


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[PMID]:27979168
[Au] Autor:Ji X; Li X; Ma Y; Li D
[Ad] Endereço:School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin, Heilongjiang 150090, China.
[Ti] Título:Differences in proteomic profiles of milk fat globule membrane in yak and cow milk.
[So] Source:Food Chem;221:1822-1827, 2017 Apr 15.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Milk fat globule membrane (MFGM) is an important milk component which is rich in bioactive proteins. In this work, the isobaric tags for relative and absolute quantitation (iTRAQ) proteomic approach was used to investigate the differences in the MFGM proteins between yak and cow milk. Over 450 proteins were identified between the yak and cow MFGM. The MFGM proteins with significant differences were compared based on the relative abundance. Proteins such as Glycosylation-dependent cell adhesion molecule 1 (GlyCAM1), CD59 molecule and lactadherin, were identified having a much higher abundance (4.6-10.1 fold) in yak MFGM than cow MFGM. These proteins are thought to have biological functions such as the antimicrobial and antitumor effects. This may be due to the need that yak produces high nutritive milk including high levels of bioactive compounds in order to resist the extreme high altitude environment.
[Mh] Termos MeSH primário: Glicolipídeos/química
Glicoproteínas/química
Leite/química
Proteômica
[Mh] Termos MeSH secundário: Animais
Antígenos CD59/química
Bovinos/classificação
Feminino
Proteínas do Leite/química
Mucinas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD59); 0 (Glycolipids); 0 (Glycoproteins); 0 (Milk Proteins); 0 (Mucins); 0 (milk fat globule); 145895-89-2 (sulfated glycoprotein p50)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170308
[Lr] Data última revisão:
170308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161216
[St] Status:MEDLINE


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[PMID]:27688119
[Au] Autor:Sui ZH; Li MF; Sun L
[Ad] Endereço:Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China; University of Chinese Academy of Sciences, Beijing, China.
[Ti] Título:Tongue sole (Cynoglossus semilaevis) CD59: A complement inhibitor that binds bacterial cells and promotes bacterial escape from the killing of fish serum.
[So] Source:Fish Shellfish Immunol;58:442-448, 2016 Nov.
[Is] ISSN:1095-9947
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:CD59 is a complement regulatory protein that inhibits the formation of membrane attack complex of complement. In this study, we examined the expression and activity of tongue sole (Cynoglossus semilaevis) CD59 (CsCD59). CsCD59 possesses the conserved structural features of CD59 and shares 33%-46% sequence identities with other fish CD59. Expression of CsCD59 was high in liver, spleen, and muscle, and was stimulated by infection of bacterial pathogens. Recombinant CsCD59 (rCsCD59) exhibited an apparent inhibition effect on the activation of tongue sole serum complement. ELISA and microscopy detected binding of rCsCD59 to a number of Gram-negative and Gram-positive bacteria. Interaction with rCsCD59 did not affect bacterial viability but significantly enhanced bacterial resistance against the killing effect of fish serum. Together these results indicate that fish CD59 may to some degrees facilitate a general escape of bacteria from complement-mediated immunity.
[Mh] Termos MeSH primário: Antígenos CD59/genética
Proteínas Inativadoras do Complemento/genética
Doenças dos Peixes/genética
Proteínas de Peixes/genética
Linguados
Infecções por Bactérias Gram-Negativas/veterinária
Infecções por Bactérias Gram-Positivas/veterinária
[Mh] Termos MeSH secundário: Animais
Antígenos CD59/metabolismo
Sequência de Bases
Proteínas Inativadoras do Complemento/metabolismo
Doenças dos Peixes/imunologia
Doenças dos Peixes/microbiologia
Proteínas de Peixes/metabolismo
Regulação da Expressão Gênica
Bactérias Gram-Negativas/fisiologia
Infecções por Bactérias Gram-Negativas/genética
Infecções por Bactérias Gram-Negativas/imunologia
Infecções por Bactérias Gram-Negativas/microbiologia
Bactérias Gram-Positivas/fisiologia
Infecções por Bactérias Gram-Positivas/genética
Infecções por Bactérias Gram-Positivas/imunologia
Infecções por Bactérias Gram-Positivas/microbiologia
Alinhamento de Sequência/veterinária
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD59); 0 (Complement Inactivator Proteins); 0 (Fish Proteins)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170302
[Lr] Data última revisão:
170302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160930
[St] Status:MEDLINE


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[PMID]:27465155
[Au] Autor:Phondeechareon T; Wattanapanitch M; U-Pratya Y; Damkham C; Klincumhom N; Lorthongpanich C; Kheolamai P; Laowtammathron C; Issaragrisil S
[Ad] Endereço:Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
[Ti] Título:Generation of induced pluripotent stem cells as a potential source of hematopoietic stem cells for transplant in PNH patients.
[So] Source:Ann Hematol;95(10):1617-25, 2016 Oct.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia caused by lack of CD55 and CD59 on blood cell membrane leading to increased sensitivity of blood cells to complement. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for PNH, however, lack of HLA-matched donors and post-transplant complications are major concerns. Induced pluripotent stem cells (iPSCs) derived from patients are an attractive source for generating autologous HSCs to avoid adverse effects resulting from allogeneic HSCT. The disease involves only HSCs and their progeny; therefore, other tissues are not affected by the mutation and may be used to produce disease-free autologous HSCs. This study aimed to derive PNH patient-specific iPSCs from human dermal fibroblasts (HDFs), characterize and differentiate to hematopoietic cells using a feeder-free protocol. Analysis of CD55 and CD59 expression was performed before and after reprogramming, and hematopoietic differentiation. Patients' dermal fibroblasts expressed CD55 and CD59 at normal levels and the normal expression remained after reprogramming. The iPSCs derived from PNH patients had typical pluripotent properties and differentiation capacities with normal karyotype. After hematopoietic differentiation, the differentiated cells expressed early hematopoietic markers (CD34 and CD43) with normal CD59 expression. The iPSCs derived from HDFs of PNH patients have normal levels of CD55 and CD59 expression and hold promise as a potential source of HSCs for autologous transplantation to cure PNH patients.
[Mh] Termos MeSH primário: Técnicas de Reprogramação Celular
Transplante de Células-Tronco Hematopoéticas
Hemoglobinúria Paroxística/terapia
Células-Tronco Pluripotentes Induzidas/citologia
[Mh] Termos MeSH secundário: Animais
Antígenos CD34/biossíntese
Antígenos CD43/biossíntese
Antígenos CD55/biossíntese
Antígenos CD59/biossíntese
Corpos Embrioides
Feminino
Fibroblastos/citologia
História do Século XVI
História do Século XVII
Humanos
Células-Tronco Pluripotentes Induzidas/transplante
Camundongos Endogâmicos BALB C
Camundongos Nus
Pele/citologia
Teratoma/patologia
Transplante Autólogo
[Pt] Tipo de publicação:HISTORICAL ARTICLE; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD34); 0 (Antigens, CD43); 0 (Antigens, CD55); 0 (Antigens, CD59); 0 (UN1 sialoglycoprotein, human)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170127
[Lr] Data última revisão:
170127
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160813
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-016-2756-1


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[PMID]:27392662
[Au] Autor:Vagace JM; Cardesa R; Corbacho A; Vázquez T; de la Maya MD; Gonzalez FA; Nieto JB; Urrutia E; Gómez MJ; Pascual T; Aguinaco MR; Gervasini G
[Ad] Endereço:Service of Hematology, Infanta Cristina University Hospital, Badajoz, Spain.
[Ti] Título:Etiopathological mechanisms and clinical characteristics of hyperhemolysis syndrome in Spanish patients with thalassemia.
[So] Source:Ann Hematol;95(9):1419-27, 2016 Sep.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Hyperhemolysis syndrome (HHS) is characterized by severe intravascular hemolysis with a decrease in the reticulocyte count, which is triggered and aggravated by transfusion and cannot be explained by standard immunohematological studies. A nationwide study was conducted in order to retrospectively identify thalassemia patients with HHS in Spain in order to assess pre-disposing mechanisms for this syndrome. For this, the expression of adhesion (CD49, CD36) and complement-related molecules (C3a, CD59) and the levels of reticulocyte apoptosis and macrophage activation were measured in 4 thalassemia patients with HHS, 14 patients without HHS, and 10 healthy subjects. Five of the six thalassemia patients had δß-thalassemia. The patients were not alloimmunized prior to the syndrome, which was developed after the first transfusion in all but one case. Patients with δß-thalassemia did not respond to corticoids or immunoglobulins; only splenectomy was successful. The expression of CD49 (α4ß1 integrin) was far higher in patients who had experienced HHS (85.07 ± 18.46 vs. 46.28 ± 24.31; p < 0.01), and the difference remained significant after correcting by the number of molecules analyzed (Bonferroni p < 0.05). In our population, δß-thalassemia was the most common hemoglobinopathy in patients with HHS. Furthermore, the risk to develop this syndrome may be associated with an increased expression of α4ß1 integrin.
[Mh] Termos MeSH primário: Transfusão de Sangue/métodos
Hemólise/fisiologia
Talassemia/fisiopatologia
Talassemia/terapia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Antígenos CD36/sangue
Antígenos CD59/sangue
Apoptose
Complemento C3a/análise
Feminino
Citometria de Fluxo
Humanos
Integrina alfa1/sangue
Ativação de Macrófagos
Masculino
Meia-Idade
Reticulócitos/metabolismo
Estudos Retrospectivos
Fatores de Risco
Espanha
Síndrome
Talassemia/sangue
Adulto Jovem
Talassemia beta/sangue
Talassemia beta/fisiopatologia
Talassemia beta/terapia
Talassemia delta/sangue
Talassemia delta/fisiopatologia
Talassemia delta/terapia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD36); 0 (Antigens, CD59); 0 (Integrin alpha1); 101754-01-2 (CD59 protein, human); 80295-42-7 (Complement C3a)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170202
[Lr] Data última revisão:
170202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160804
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-016-2733-8


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[PMID]:27170144
[Au] Autor:Heider S; Kleinberger S; Kochan F; Dangerfield JA; Metzner C
[Ad] Endereço:Institute of Virology, University of Veterinary Medicine, Veterinärplatz 1, 1210, Vienna, Austria.
[Ti] Título:Immune Protection of Retroviral Vectors Upon Molecular Painting with the Complement Regulatory Protein CD59.
[So] Source:Mol Biotechnol;58(7):480-8, 2016 Jul.
[Is] ISSN:1559-0305
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glycosylphosphatidylinositol anchoring is a type of post-translational modification that allows proteins to be presented on the exterior side of the cell membrane. Purified glycosylphosphatidylinositol-anchored protein can spontaneously re-insert into lipid bilayer membranes in a process termed Molecular Painting. Here, we demonstrate the possibility of inserting purified, recombinant CD59 into virus particles produced from a murine retroviral producer cell line. CD59 is a regulator of the complement system that helps protect healthy cells from the lytic activity of the complement cascade. In this study, we could show that Molecular Painting confers protection from complement activity upon murine retroviral vector particles. Indeed, increased infectivity of CD59-modified virus particles was observed upon challenge with human serum, indicating that Molecular Painting is suitable for modulating the immune system in gene therapy or vaccination applications.
[Mh] Termos MeSH primário: Antígenos CD59/metabolismo
Glicosilfosfatidilinositóis/química
Bicamadas Lipídicas/metabolismo
Vírion/imunologia
[Mh] Termos MeSH secundário: Animais
Antígenos CD59/química
Antígenos CD59/genética
Linhagem Celular
Ativação do Complemento
Células HeLa
Humanos
Camundongos
Células NIH 3T3
Processamento de Proteína Pós-Traducional
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Retroviridae/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD59); 0 (Glycosylphosphatidylinositols); 0 (Lipid Bilayers); 0 (Recombinant Proteins); 101754-01-2 (CD59 protein, human)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170309
[Lr] Data última revisão:
170309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160609
[St] Status:MEDLINE
[do] DOI:10.1007/s12033-016-9944-z


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[PMID]:27056040
[Au] Autor:Bahia El Idrissi N; Bosch S; Ramaglia V; Aronica E; Baas F; Troost D
[Ad] Endereço:Department of Genome Analysis, Academic Medical Center, Amsterdam, 1105 AZ, The Netherlands.
[Ti] Título:Complement activation at the motor end-plates in amyotrophic lateral sclerosis.
[So] Source:J Neuroinflammation;13(1):72, 2016 Apr 07.
[Is] ISSN:1742-2094
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease with no available therapy. Components of the innate immune system are activated in the spinal cord and central nervous system of ALS patients. Studies in the SOD1(G93A) mouse show deposition of C1q and C3/C3b at the motor end-plate before neurological symptoms are apparent, suggesting that complement activation precedes neurodegeneration in this model. To obtain a better understanding of the role of complement at the motor end-plates in human ALS pathology, we analyzed post-mortem tissue of ALS donors for complement activation and its regulators. METHODS: Post-mortem intercostal muscle biopsies were collected at autopsy from ALS (n = 11) and control (n = 6) donors. The samples were analyzed for C1q, membrane attack complex (MAC), CD55, and CD59 on the motor end-plates, using immunofluorescence or immunohistochemistry. RESULTS: Here, we show that complement activation products and regulators are deposited on the motor end-plates of ALS patients. C1q co-localized with neurofilament in the intercostal muscle of ALS donors and was absent in controls (P = 0.001). In addition, C1q was found deposited on the motor end-plates in the intercostal muscle. MAC was also found deposited on motor end-plates that were innervated by nerves in the intercostal muscle of ALS donors but not in controls (P = 0.001). High levels of the regulators CD55 and CD59 were detected at the motor end-plates of ALS donors but not in controls, suggesting an attempt to counteract complement activation and prevent MAC deposition on the end-plates before they are lost. CONCLUSIONS: This study provides evidence that complement activation products are deposited on innervated motor end-plates in the intercostal muscle of ALS donors, indicating that complement activation may precede end-plate denervation in human ALS. This study adds to the understanding of ALS pathology in man and identifies complement as a potential modifier of the disease process.
[Mh] Termos MeSH primário: Esclerose Amiotrófica Lateral/fisiopatologia
Ativação do Complemento
Placa Motora
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Animais
Antígenos CD55/metabolismo
Antígenos CD59/metabolismo
Biópsia
Complemento C1q/metabolismo
Complexo de Ataque à Membrana do Sistema Complemento/metabolismo
Feminino
Humanos
Músculos Intercostais/patologia
Masculino
Camundongos
Meia-Idade
Proteínas de Neurofilamentos/metabolismo
Superóxido Dismutase-1/genética
Superóxido Dismutase-1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD55); 0 (Antigens, CD59); 0 (Complement Membrane Attack Complex); 0 (Neurofilament Proteins); 80295-33-6 (Complement C1q); EC 1.15.1.1 (Sod1 protein, mouse); EC 1.15.1.1 (Superoxide Dismutase-1)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170214
[Lr] Data última revisão:
170214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160408
[St] Status:MEDLINE
[do] DOI:10.1186/s12974-016-0538-2


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[PMID]:26978230
[Au] Autor:Saryeva OP; Salakhova LM; Kulida LV; Malyshkina AI
[Ad] Endereço:Laboratory of Pathomorphology and Electron Microscopy, V.N. Gorodkov Ivanovo Research Institute of Maternity and Childhood, Ministry of Health of Russia, Ivanovo, Russia.
[Ti] Título:[Immunomorphological aspects of miscarriage at late gestational ages].
[So] Source:Arkh Patol;78(1):8-12, 2016 Jan-Feb.
[Is] ISSN:0004-1955
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:AIM: to reveal the morphological features of placentas and to define a role of the lectin pathway for activation of the complement system in the development of premature birth. MATERIAL AND METHODS: A complex morphological study was conducted to examine 37 placentas, 25 of which were obtained from women with clinical signs of threatened miscarriage and 12 placentas from apparently healthy pregnant women. RESULTS: Placental tissue CD59 expression was ascertained to be significantly less in the women with threatened miscarriage than in those having full-term babies. CONCLUSION: Decreased CD59 expression in threatened miscarriage at late gestational ages leads to additional activation of a maternal immune response and serves as a possible predictor for premature birth.
[Mh] Termos MeSH primário: Aborto Espontâneo/genética
Antígenos CD59/biossíntese
Nascimento Prematuro/genética
[Mh] Termos MeSH secundário: Aborto Espontâneo/patologia
Adulto
Antígenos CD59/genética
Feminino
Regulação da Expressão Gênica no Desenvolvimento
Idade Gestacional
Humanos
Placenta/metabolismo
Placenta/patologia
Gravidez
Nascimento Prematuro/patologia
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD59); 101754-01-2 (CD59 protein, human)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:160316
[Lr] Data última revisão:
160316
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160316
[St] Status:MEDLINE



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