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  1 / 1637 MEDLINE  
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[PMID]:28742139
[Au] Autor:Hovingh ES; van den Broek B; Kuipers B; Pinelli E; Rooijakkers SHM; Jongerius I
[Ad] Endereço:Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
[Ti] Título:Acquisition of C1 inhibitor by Bordetella pertussis virulence associated gene 8 results in C2 and C4 consumption away from the bacterial surface.
[So] Source:PLoS Pathog;13(7):e1006531, 2017 Jul.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Whooping cough, or pertussis, is a contagious disease of the respiratory tract that is re-emerging worldwide despite high vaccination coverage. The causative agent of this disease is the Gram-negative Bordetella pertussis. Knowledge on complement evasion strategies of this pathogen is limited. However, this is of great importance for future vaccine development as it has become apparent that a novel pertussis vaccine is needed. Here, we unravel the effect of Virulence associated gene 8 (Vag8) of B. pertussis on the human complement system at the molecular level. We show that both recombinant and endogenously secreted Vag8 inhibit complement deposition on the bacterial surface at the level of C4b. We reveal that Vag8 binding to human C1-inhibitor (C1-inh) interferes with the binding of C1-inh to C1s, C1r and MASP-2, resulting in the release of active proteases that subsequently cleave C2 and C4 away from the bacterial surface. We demonstrate that the depletion of these complement components in the bacterial surrounding and subsequent decreased deposition on B. pertussis leads to less complement-mediated bacterial killing. Vag8 is the first protein described that specifically prevents C1s, C1r and MASP-2 binding to C1-inh and thereby mediates complement consumption away from the bacterial surface. Unravelling the mechanism of this unique complement evasion strategy of B. pertussis is one of the first steps towards understanding the interactions between the first line of defense complement and B. pertussis.
[Mh] Termos MeSH primário: Proteínas de Bactérias/imunologia
Bordetella pertussis/imunologia
Complemento C1/imunologia
Complemento C2/imunologia
Complemento C4/imunologia
Fatores de Virulência de Bordetella/imunologia
Coqueluche/imunologia
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Bordetella pertussis/genética
Seres Humanos
Virulência
Fatores de Virulência de Bordetella/genética
Coqueluche/microbiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Complement C1); 0 (Complement C2); 0 (Complement C4); 0 (Virulence Factors, Bordetella)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006531


  2 / 1637 MEDLINE  
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[PMID]:28832655
[Au] Autor:Danobeitia JS; Ziemelis M; Ma X; Zitur LJ; Zens T; Chlebeck PJ; Van Amersfoort ES; Fernandez LA
[Ad] Endereço:Department of Surgery, Division of Transplantation, University of Wisconsin-Madison, Madison, WI, United States of America.
[Ti] Título:Complement inhibition attenuates acute kidney injury after ischemia-reperfusion and limits progression to renal fibrosis in mice.
[So] Source:PLoS One;12(8):e0183701, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The complement system is an essential component of innate immunity and plays a major role in the pathogenesis of ischemia-reperfusion injury (IRI). In this study, we investigated the impact of human C1-inhibitor (C1INH) on the early inflammatory response to IRI and the subsequent progression to fibrosis in mice. We evaluated structural damage, renal function, acute inflammatory response, progression to fibrosis and overall survival at 90-days post-injury. Animals receiving C1INH prior to reperfusion had a significant improvement in survival rate along with superior renal function when compared to vehicle (PBS) treated counterparts. Pre-treatment with C1INH also prevented acute IL-6, CXCL1 and MCP-1 up-regulation, C5a release, C3b deposition and infiltration by neutrophils and macrophages into renal tissue. This anti-inflammatory effect correlated with a significant reduction in the expression of markers of fibrosis alpha smooth muscle actin, desmin and picrosirius red at 30 and 90 days post-IRI and reduced renal levels of TGF-ß1 when compared to untreated controls. Our findings indicate that intravenous delivery of C1INH prior to ischemic injury protects kidneys from inflammatory injury and subsequent progression to fibrosis. We conclude that early complement blockade in the context of IRI constitutes an effective strategy in the prevention of fibrosis after ischemic acute kidney injury.
[Mh] Termos MeSH primário: Lesão Renal Aguda/prevenção & controle
Complemento C1/antagonistas & inibidores
Inativadores do Complemento/farmacologia
Nefropatias/patologia
Traumatismo por Reperfusão/complicações
[Mh] Termos MeSH secundário: Lesão Renal Aguda/etiologia
Animais
Complemento C1/fisiologia
Modelos Animais de Doenças
Progressão da Doença
Fibrose
Masculino
Camundongos
Camundongos Endogâmicos C57BL
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Complement C1); 0 (Complement Inactivating Agents)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170824
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183701


  3 / 1637 MEDLINE  
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[PMID]:28407005
[Au] Autor:Panayiotou E; Fella E; Papacharalambous R; Malas S; Saraiva MJ; Kyriakides T
[Ad] Endereço:Clinic A, Neuropathology Department, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus.
[Ti] Título:C1q ablation exacerbates amyloid deposition: A study in a transgenic mouse model of ATTRV30M amyloid neuropathy.
[So] Source:PLoS One;12(4):e0175767, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:ATTRV30M amyloid neuropathy is a lethal autosomal dominant sensorimotor and autonomic neuropathy, caused by deposition of amyloid fibrils composed of aberrant transthyretin (TTR). Ages of onset and penetrance exhibit great variability and genetic factors have been implicated. Complement activation co-localizes with amyloid deposits in amyloidotic neuropathy and is possibly involved in the kinetics of amyloidogenesis. A candidate gene approach has recently identified C1q polymorphisms to correlate with disease onset in a Cypriot cohort of patients with ATTRV30M amyloid neuropathy. In the current study we use a double transgenic mouse model of ATTRV30M amyloid neuropathy in which C1q is ablated to elucidate further a possible modifier role for C1q. Amyloid deposition is found to be increased by 60% in the absence of C1q. Significant up regulation is also recorded in apoptotic and cellular stress markers reflecting extracellular toxicity of pre-fibrillar and fibrillar TTR. Our data further indicate that in the absence of C1q there is marked reduction of macrophages in association with amyloid deposits and thus less effective phagocytosis of TTR.
[Mh] Termos MeSH primário: Neuropatias Amiloides Familiares/patologia
Amiloide/metabolismo
Complemento C1/deficiência
Pré-Albumina/genética
[Mh] Termos MeSH secundário: Neuropatias Amiloides Familiares/genética
Neuropatias Amiloides Familiares/metabolismo
Animais
Apoptose
Modelos Animais de Doenças
Feminino
Seres Humanos
Camundongos
Camundongos Transgênicos
Mutação
Pré-Albumina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid); 0 (Complement C1); 0 (Prealbumin)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170504
[Lr] Data última revisão:
170504
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170414
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0175767


  4 / 1637 MEDLINE  
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[PMID]:28107369
[Au] Autor:Neuchel C; Fürst D; Niederwieser D; Bunjes D; Tsamadou C; Wulf G; Pfreundschuh M; Wagner E; Stuhler G; Einsele H; Schrezenmeier H; Mytilineos J
[Ad] Endereço:Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden Wuerttenberg-Hessen and University Hospital of Ulm, Ulm, Germany.
[Ti] Título:Impact of Donor Activating KIR Genes on HSCT Outcome in C1-Ligand Negative Myeloid Disease Patients Transplanted with Unrelated Donors-A Retrospective Study.
[So] Source:PLoS One;12(1):e0169512, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Natural Killer cells (NK) are lymphocytes with the potential to recognize and lyse cells which escaped T-cell mediated lysis due to their aberrant HLA expression profiles. Killer cell immunoglobulin-like receptors (KIR) influence NK-cell activity by mediation of activating or inhibitory signals upon interaction with HLA-C (C1, C2) ligands. Therefore, absence of ligands for donor inhibitory KIRs following hematopoietic stem cell transplantation (HSCT) may have an influence on its outcome. Previous studies showed that C1 negative patients have a decreased HSCT outcome. Our study, based on a cohort of 200 C1-negative patients, confirmed these findings for the endpoints: overall survival (OS: HR = 1.41, CI = 1.14-1.74, p = 0.0012), disease free survival (DFS: HR = 1.27, CI = 1.05-1.53, p = 0.015), treatment related mortality (TRM: HR = 1.41, CI = 1.01-1.96, p = 0.04), and relapse incidence (RI: HR = 1.33, CI = 1.01-1.75, p = 0.04) all being inferior when compared to C1-positive patients (n = 1246). Subsequent analysis showed that these findings applied for patients with myeloid malignancies but not for patients with lymphoproliferative diseases (OS: myeloid: HR = 1.51, CI = 1.15-1.99, p = 0.003; lymphoblastic: HR = 1.26, CI = 0.91-1.75, p = 0.16; DFS: myeloid: HR = 1.31, CI = 1.01-1.70, p = 0.04; lymphoblastic: HR = 1.21, CI = 0.90-1.61, p = 0.21; RI: myeloid: HR = 1.31, CI = 1.01-1.70, p = 0.04; lymphoblastic: HR = 1.21, CI = 0.90-1.61, p = 0.21). Interestingly, within the C1-negative patient group, transplantation with KIR2DS2 resulted in better OS (9/10 matched: HR = 0.24, CI = 0.08-0.67, p = 0.007) as well as DFS (9/10 matched: HR = 0,26, CI = 0.11-0.60, p = 0.002), and transplantation with KIR2DS1 positive donors was associated with a decreased RI (HR = 0.30, CI = 0.13-0.69, p = 0.005). TRM was increased when the donor was positive for KIR2DS1 (HR = 2.61, CI = 1.26-5.41, p = 0.001). Our findings suggest that inclusion of KIR2DS1/2/5 and KIR3DS1-genotyping in the unrelated donor search algorithm of C1-ligand negative patients with myeloid malignancies may prove to be of clinical relevance.
[Mh] Termos MeSH primário: Neoplasias Hematológicas/terapia
Transplante de Células-Tronco Hematopoéticas
Receptores KIR/genética
Doadores não Relacionados
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Estudos de Coortes
Complemento C1/metabolismo
Feminino
Seres Humanos
Células Matadoras Naturais/imunologia
Ligantes
Masculino
Meia-Idade
Estudos Retrospectivos
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Complement C1); 0 (Ligands); 0 (Receptors, KIR)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170810
[Lr] Data última revisão:
170810
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170121
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0169512


  5 / 1637 MEDLINE  
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[PMID]:27895277
[Au] Autor:Weinberger K; Collazo N; Aguillón JC; Molina MC; Rosas C; Peña J; Pizarro J; Maldonado I; Cattan PE; Apt W; Ferreira A
[Ad] Endereço:Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
[Ti] Título: Calreticulin: Gene Cloning and Expression of a Main Domain That Interacts with the Host Complement System.
[So] Source:Am J Trop Med Hyg;96(2):295-303, 2017 Feb 08.
[Is] ISSN:1476-1645
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:is an important hematophagous vector of Chagas disease, a neglected chronic illness affecting approximately 6 million people in Latin America. Hematophagous insects possess several molecules in their saliva that counteract host defensive responses. Calreticulin (CRT), a multifunctional protein secreted in saliva, contributes to the feeding process in some insects. Human CRT (HuCRT) and CRT (TcCRT) inhibit the classical pathway of complement activation, mainly by interacting through their central S domain with complement component C1. In previous studies, we have detected CRT in salivary gland extracts from We have called this molecule TiCRT. Given that the S domain is responsible for C1 binding, we have tested its role in the classical pathway of complement activation in vertebrate blood. We have cloned and characterized the complete nucleotide sequence of CRT from , and expressed its S domain. As expected, this S domain binds to human C1 and, as a consequence, it inhibits the classical pathway of complement, at its earliest stage of activation, namely the generation of C4b. Possibly, the presence of TiCRT in the salivary gland represents an evolutionary adaptation in hematophagous insects to control a potential activation of complement proteins, present in the massive blood meal that they ingest, with deleterious consequences at least on the anterior digestive tract of these insects.
[Mh] Termos MeSH primário: Calreticulina/genética
Proteínas do Sistema Complemento/imunologia
Interações Hospedeiro-Parasita/genética
Triatoma/genética
[Mh] Termos MeSH secundário: Animais
Galinhas/parasitologia
Clonagem Molecular
Complemento C1/imunologia
Expressão Gênica
Alinhamento de Sequência
Análise de Sequência de DNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calreticulin); 0 (Complement C1); 9007-36-7 (Complement System Proteins)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170522
[Lr] Data última revisão:
170522
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161130
[St] Status:MEDLINE
[do] DOI:10.4269/ajtmh.16-0642


  6 / 1637 MEDLINE  
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[PMID]:27807190
[Au] Autor:Engelberts PJ; Voorhorst M; Schuurman J; van Meerten T; Bakker JM; Vink T; Mackus WJ; Breij EC; Derer S; Valerius T; van de Winkel JG; Parren PW; Beurskens FJ
[Ad] Endereço:Genmab, 3584 CM Utrecht, the Netherlands.
[Ti] Título:Type I CD20 Antibodies Recruit the B Cell Receptor for Complement-Dependent Lysis of Malignant B Cells.
[So] Source:J Immunol;197(12):4829-4837, 2016 Dec 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human IgG1 type I CD20 Abs, such as rituximab and ofatumumab (OFA), efficiently induce complement-dependent cytotoxicity (CDC) of CD20 B cells by binding of C1 to hexamerized Fc domains. Unexpectedly, we found that type I CD20 Ab F(ab') fragments, as well as C1q-binding-deficient IgG mutants, retained an ability to induce CDC, albeit with lower efficiency than for whole or unmodified IgG. Experiments using human serum depleted of specific complement components demonstrated that the observed lytic activity, which we termed "accessory CDC," remained to be dependent on C1 and the classical pathway. We hypothesized that CD20 Ab-induced clustering of the IgM or IgG BCR was involved in accessory CDC. Indeed, accessory CDC was consistently observed in B cell lines expressing an IgM BCR and in some cell lines expressing an IgG BCR, but it was absent in BCR B cell lines. A direct relationship between BCR expression and accessory CDC was established by transfecting the BCR into CD20 cells: OFA-F(ab') fragments were able to induce CDC in the CD20 BCR cell population, but not in the CD20 BCR population. Importantly, OFA-F(ab') fragments were able to induce CDC ex vivo in malignant B cells isolated from patients with mantle cell lymphoma and Waldenström macroglobulinemia. In summary, accessory CDC represents a novel effector mechanism that is dependent on type I CD20 Ab-induced BCR clustering. Accessory CDC may contribute to the excellent capacity of type I CD20 Abs to induce CDC, and thereby to the antitumor activity of such Abs in the clinic.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/metabolismo
Citotoxicidade Celular Dependente de Anticorpos
Antígenos CD20/metabolismo
Linfócitos B/efeitos dos fármacos
Via Clássica do Complemento
Imunoterapia Adotiva/métodos
Linfoma de Células B/terapia
Rituximab/metabolismo
[Mh] Termos MeSH secundário: Anticorpos Monoclonais/genética
Anticorpos Monoclonais/uso terapêutico
Antígenos CD20/imunologia
Linfócitos B/imunologia
Linhagem Celular Tumoral
Complemento C1/metabolismo
Seres Humanos
Fragmentos Fab das Imunoglobulinas/metabolismo
Imunoglobulina G/genética
Imunoglobulina G/metabolismo
Imunoglobulina M/genética
Imunoglobulina M/metabolismo
Linfoma de Células B/imunologia
Receptores de Antígenos de Linfócitos B/genética
Receptores de Antígenos de Linfócitos B/metabolismo
Rituximab/genética
Rituximab/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antigens, CD20); 0 (Complement C1); 0 (Immunoglobulin Fab Fragments); 0 (Immunoglobulin G); 0 (Immunoglobulin M); 0 (Receptors, Antigen, B-Cell); 4F4X42SYQ6 (Rituximab); M95KG522R0 (ofatumumab)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170811
[Lr] Data última revisão:
170811
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161104
[St] Status:MEDLINE


  7 / 1637 MEDLINE  
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[PMID]:27591336
[Au] Autor:Garcia BL; Zwarthoff SA; Rooijakkers SH; Geisbrecht BV
[Ad] Endereço:Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS 66506; and.
[Ti] Título:Novel Evasion Mechanisms of the Classical Complement Pathway.
[So] Source:J Immunol;197(6):2051-60, 2016 Sep 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Complement is a network of soluble and cell surface-associated proteins that gives rise to a self-amplifying, yet tightly regulated system with fundamental roles in immune surveillance and clearance. Complement becomes activated on the surface of nonself cells by one of three initiating mechanisms known as the classical, lectin, and alternative pathways. Evasion of complement function is a hallmark of invasive pathogens and hematophagous organisms. Although many complement-inhibition strategies hinge on hijacking activities of endogenous complement regulatory proteins, an increasing number of uniquely evolved evasion molecules have been discovered over the past decade. In this review, we focus on several recent investigations that revealed mechanistically distinct inhibitors of the classical pathway. Because the classical pathway is an important and specific mediator of various autoimmune and inflammatory disorders, in-depth knowledge of novel evasion mechanisms could direct future development of therapeutic anti-inflammatory molecules.
[Mh] Termos MeSH primário: Via Clássica do Complemento
Evasão da Resposta Imune
[Mh] Termos MeSH secundário: Animais
Complemento C1/fisiologia
Complemento C1q/fisiologia
Convertases de Complemento C3-C5/antagonistas & inibidores
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Complement C1); 80295-33-6 (Complement C1q); EC 3.4.21.- (Complement C3-C5 Convertases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170924
[Lr] Data última revisão:
170924
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:160904
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1600863


  8 / 1637 MEDLINE  
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[PMID]:27391278
[Au] Autor:Yuan H; Chen R; Tariq M; Liu Y; Sun Y; Xia C
[Ad] Endereço:Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, People's Republic of China.
[Ti] Título:Crystal structure of zebrafish complement 1qA globular domain.
[So] Source:Protein Sci;25(10):1883-9, 2016 Oct.
[Is] ISSN:1469-896X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:C1q contains three globular domains (C1qgD) that are the key functional component of the classical complement system. C1qgD can interact with important immune molecules, including IgG and C-reactive protein (CRP) to form defense systems to protect animals. Here, the first non-mammalian structure, zebrafish C1qA globular domain (Dare-C1qAgD) was solved. Although the overall architecture of Dare-C1qAgD is similar to human C1qA, residues involved in C1qBgD, C1qCgD, and CRP binding are somewhat different while residues involved in IgG binding are not present in zebrafish. The structure gives insight into how human and fish C1qA evolved from an ancestral protein.
[Mh] Termos MeSH primário: Complemento C1/química
Evolução Molecular
Proteínas de Peixe-Zebra/química
Peixe-Zebra
[Mh] Termos MeSH secundário: Animais
Cristalografia por Raios X
Seres Humanos
Domínios Proteicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Complement C1); 0 (Zebrafish Proteins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171001
[Lr] Data última revisão:
171001
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160709
[St] Status:MEDLINE
[do] DOI:10.1002/pro.2980


  9 / 1637 MEDLINE  
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[PMID]:27282513
[Au] Autor:Kumar PS; Pallera HK; Hair PS; Rivera MG; Shah TA; Werner AL; Lattanzio FA; Cunnion KM; Krishna NK
[Ad] Endereço:Department of Pediatrics.
[Ti] Título:Peptide inhibitor of complement C1 modulates acute intravascular hemolysis of mismatched red blood cells in rats.
[So] Source:Transfusion;56(8):2133-45, 2016 Aug.
[Is] ISSN:1537-2995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Acute hemolytic transfusion reactions have a broad clinical presentation from mild and transitory signs and symptoms to shock, disseminated intravascular coagulation, renal failure, and death. We have recently developed a rat model of acute intravascular hemolysis showing that the classical complement pathway mediates antibody-dependent hemolysis. The objective of this study was to evaluate the role of the classical pathway inhibitor peptide inhibitor of complement C1 (PIC1) in this animal model. STUDY DESIGN AND METHODS: Male Wistar rats received a 15% transfusion of human red blood cells (RBCs) and blood was isolated from the animals up to 120 minutes. Animals received PIC1 either 2 minutes before or 0.5 minutes after transfusion. Sham-, vehicle-, and cobra venom factor (CVF)-treated animals were used as control groups with a subset of rats also receiving an equivalent dose of intravenous immunoglobulin (IVIG) before transfusion. Blood was analyzed for transfused RBC survival by flow cytometry and free hemoglobin (Hb) in isolated plasma by spectrophotometry. RESULTS: Vehicle-treated rats showed decreased human RBC survival and increased free Hb as expected. Rats receiving PIC1 before transfusion showed increased human RBC survival and decreased Hb similar to CVF-treated rats. Notably, rats receiving PIC1 after initiation of transfusion showed similar decreases in hemolysis as animals receiving PIC1 before transfusion. Compared to IVIG and saline controls, PIC1-treated animals demonstrated decreased hemolysis and protection from acute kidney injury. CONCLUSIONS: These results demonstrate that PIC1 has efficacy in an animal model of acute intravascular hemolysis in both prevention and rescue scenarios.
[Mh] Termos MeSH primário: Complemento C1/antagonistas & inibidores
Hemólise/efeitos dos fármacos
Peptídeos/farmacologia
[Mh] Termos MeSH secundário: Animais
Incompatibilidade de Grupos Sanguíneos/tratamento farmacológico
Contagem de Eritrócitos
Eritrócitos/citologia
Eritrócitos/efeitos dos fármacos
Hemoglobinas/metabolismo
Seres Humanos
Masculino
Peptídeos/uso terapêutico
Ratos
Ratos Wistar
Reação Transfusional/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Complement C1); 0 (Hemoglobins); 0 (Peptides)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170619
[Lr] Data última revisão:
170619
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160611
[St] Status:MEDLINE
[do] DOI:10.1111/trf.13674


  10 / 1637 MEDLINE  
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[PMID]:26840927
[Au] Autor:Schaefer SM; Süsal C; Opelz G; Döhler B; Becker LE; Klein K; Sickmüller S; Waldherr R; Macher-Goeppinger S; Schemmer P; Beimler J; Zeier M; Morath C
[Ad] Endereço:Division of Nephrology, University Hospital of Heidelberg, Heidelberg, Germany.
[Ti] Título:Pre-transplant soluble CD30 in combination with total DSA but not pre-transplant C1q-DSA predicts antibody-mediated graft loss in presensitized high-risk kidney transplant recipients.
[So] Source:HLA;87(2):89-99, 2016 Feb.
[Is] ISSN:2059-2310
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Presensitized kidney transplant recipients are at high-risk for early antibody-mediated rejection. We studied the impact of pre- and post-transplant donor-specific human leukocyte antigen (HLA) antibodies (DSA) and T-cell-activation on the occurrence of antibody-mediated rejection episodes (AMR) and graft loss (AMR-GL) in a unique cohort of 80 desensitized high-risk kidney transplant recipients. Patients with pre-transplant DSA demonstrated more AMR episodes than patients without DSA, but did not show a significantly increased rate of AMR-GL. The rates of AMR and AMR-GL were not significantly increased in patients with complement split product (C1q)-binding pre-transplant DSA. Pre-transplant C1q-DSA became undetectable post-transplant in 11 of 13 (85%) patients; 2 (18%) of these 11 patients showed AMR but no AMR-GL. In contrast, the post-transplant presence of C1q-DSA was associated with significantly higher rates of AMR (86 vs 33 vs 0%; P < 0.001) and AMR-GL (86 vs 0 vs 0%; log-rank P < 0.001) compared with post-transplant DSA without C1q-binding or the absence of DSA. Patients with both pre-transplant DSA and evidence of pre-transplant T-cell-activation as indicated by soluble CD30-positivity showed a significantly increased risk for AMR-GL [HR = 11.1, 95% confidence interval (CI) = 1.68-73.4; log-rank P = 0.013]. In these high-risk patients, AMR-GL was associated with total DSA in combination with T-cell-activation pre-transplant, and de novo or persistent C1q-binding DSA post-transplant.
[Mh] Termos MeSH primário: Rejeição de Enxerto/sangue
Isoanticorpos/sangue
Antígeno Ki-1/sangue
Transplante de Rim
Ativação Linfocitária
Período Pré-Operatório
Linfócitos T/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Complemento C1/imunologia
Complemento C1/metabolismo
Feminino
Rejeição de Enxerto/imunologia
Seres Humanos
Isoanticorpos/imunologia
Antígeno Ki-1/imunologia
Masculino
Meia-Idade
Valor Preditivo dos Testes
Linfócitos T/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Complement C1); 0 (Isoantibodies); 0 (Ki-1 Antigen)
[Em] Mês de entrada:1611
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160204
[St] Status:MEDLINE
[do] DOI:10.1111/tan.12735



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