A monoclonal IgG anticardiolipin antibody from a patient with the antiphospholipid syndrome is thrombogenic in mice.

Antiphospholipid antibodies, including anticardiolipin antibodies (ACA), are strongly associated with recurrent thrombosis in patients with the antiphospholipid syndrome (APS). To date, reports about the binding specificities of ACA and their role(s) in causing and/or sustaining thrombosis in APS are conflicting and controversial. The plasmas of patients with APS, usually containing a mixture of autoantibodies, vary in binding specificity for different phospholipids/cofactors and vary in in vitro lupus anticoagulant activity. Although in vivo assays that allow assessment of the pathogenic procoagulant activity of patient autoantibodies have recently been developed, the complex nature of the mixed species prevented determination of the particular species responsible for in vivo thrombosis. We have generated two human IgG monoclonal ACA from an APS patient with recurrent thrombosis. Both bound to cardiolipin in the presence of 10% bovine serum, but not in its absence, and both were reactive against phosphatidic acid, but were nonreactive against purified human beta-2 glycoprotein 1, DNA, heparan sulfate, or four other test antigens. Both monoclonal autoantibodies lacked lupus anticoagulant activity and did not inhibit prothrombinase activity. Remarkably, one of the monoclonal antibodies has thrombogenic properties when tested in an in vivo mouse model. This finding provides the first direct evidence that a particular antiphospholipid antibody specificity may contribute to in vivo thrombosis.

A Fas-associated protein factor, FAF1, potentiates Fas-mediated apoptosis.

Fas, a member of the tumor necrosis factor receptor family, can induce apoptosis when activated by Fas ligand binding or anti-Fas antibody crosslinking. Genetic studies have shown that a defect in Fas-mediated apoptosis resulted in abnormal development and function of the immune system in mice. A point mutation in the cytoplasmic domain of Fas (a single base change from T to A at base 786), replacing isoleucine with asparagine, abolishes the signal transducing property of Fas. Mice homozygous for this mutant allele (lprcg/lprcg mice) develop lymphadenopathy and a lupus-like autoimmune disease. Little is known about the mechanism of signal transduction in Fas-mediated apoptosis. In this study, we used the two-hybrid screen in yeast to isolate a Fas-associated protein factor, FAF1, which specifically interacts with the cytoplasmic domain of wild-type Fas but not the lprcg-mutated Fas protein. This interaction occurs not only in yeast but also in mammalian cells. When transiently expressed in L cells, FAF1 potentiated Fas-induced apoptosis. A search of available DNA and protein sequence data banks did not reveal significant homology between FAF1 and known proteins. Therefore, FAF1 is an unusual protein that binds to the wild type but not the inactive point mutant of Fas. FAF1 potentiates Fas-induced cell killing and is a candidate signal transducing molecule in the regulation of apoptosis.

Lúpus eritematoso neonatal

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

A hipertensão pulmonar como consequência de lúpus na gravidez : caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Leishmaniose em Lobo Ibérico

Quando falamos de vida selvagem em Portugal, pensamos logo no Lobo Ibérico (Canis lupus signatus), que ao longo das últimas décadas tem vindo a sofrer um notório declínio populacional, apenas contrariado pelas medidas protecionistas entretanto implementadas. A diminuição do número de lobos em Portugal resulta principalmente da perseguição direta a que foram sujeitos e da destruição do seu habitat natural. Outra causa de redução/extinção de pequenas populações locais e fragmentadas de grandes carnívoros em outras partes no mundo tem sido as doenças infeciosas. Sendo monitorização da presença de patologias em animais silvestres fundamental no controle das zoonoses emergentes e na conservação das espécies. Neste contexto pretendeu-se elaborar um estudo de determinação da ocorrência de Leishmaniose, no Lobo Ibérico. Assim, recolheram-se aleatoriamente 42 amostras de sangue a lobos residentes no Parque Nacional Peneda-Gerês que, posteriormente foram testadas recorrendo-se ao método de ELISA. Através desta técnica, detetou-se que das 42 amostras testadas apenas uma amostra (2,4%) possuía anticorpos anti-leishmania. Um dos motivos para a obtenção de resultados pouco significativos poderá dever-se ao reduzido leque amostral. Concluímos, então, que são necessários estudos adicionais para avaliar a importância do Lobo Ibérico na transmissão e propagação da Leishmaniose.

Divinum ac immobile Sancti Petri ... circa omnium sub coelo fidelium ad Romanam eius Cathedram Apellationes adversum profanas hodie vocum novitates assertum privilegium /

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Synodorum generalium ac provincialium decreta, et canones /

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Synodorum generalium ac provincialium decreta et canones /

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Synodorum generalium ac provincialium decreta et canones /

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Q. Florentis Septimii Tertulliani ... Liber de Praescriptionibus contra Haereticos /

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Synodorum generalium ac provincialium decreta et canones /

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Synodorum generalium ac provincialium decreta et canones /

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Ad Ephesinum Concilium Variorum Patrum Epistolae : ex manu-scripto Cassinensis Bibliothecae Codice desumptae : item ex Vaticanae Bibliothecae manu-scripto ... nunc primum in publicam lucem data /

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Synodorum generalium ac provincialium decreta, et canones /

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