Search results for "Factor H"

Genetic prediction of ICU hospitalization and mortality in COVID‐19 patients using artificial neural networks

2021

There is an unmet need of models for early prediction of morbidity and mortality of Coronavirus disease-19 (COVID-19). We aimed to a) identify complement-related genetic variants associated with the clinical outcomes of ICU hospitalization and death, b) develop an artificial neural network (ANN) predicting these outcomes and c) validate whether complement-related variants are associated with an impaired complement phenotype. We prospectively recruited consecutive adult patients of Caucasian origin, hospitalized due to COVID-19. Through targeted next-generation sequencing, we identified variants in complement factor H/CFH, CFB, CFH-related, CFD, CD55, C3, C5, CFI, CD46, thrombomodulin/THBD, …

Molecular basis for factor H and FHL-1 deficiency in an Italian family

2000

Expression pattern of Notch1, 2 and 3 and Jagged1 and 2 in lymphoid and stromal thymus components: distinct ligand–receptor interactions in intrathym…

1999

The suggested role of Notch1 or its mutants in thymocyte differentiation and T cell tumorigenesis raises the question of how the different members of the Notch family influence distinct steps in T cell development and the role played by Notch ligands in the thymus. We report here that different Notch receptor-ligand partnerships may occur inside the thymus, as we observed differential expression of Notch1, 2 and 3 receptors, their ligands Jagged1 and 2, and downstream intracellular effectors hairy and Enhancer of Split homolog 1 (HES-1) and hairy and Enhancer of Split homolog 5 (HES-5), depending on ontogenetic stage and thymic cell populations. Indeed, while Jagged2 is expressed in both st…

Dynamics of complement activation in aHUS and how to monitor eculizumab therapy.

2014

Atypical hemolytic-uremic syndrome (aHUS) is associated with genetic complement abnormalities/anti–complement factor H antibodies, which paved the way to treatment with eculizumab. We studied 44 aHUS patients and their relatives to (1) test new assays of complement activation, (2) verify whether such abnormality occurs also in unaffected mutation carriers, and (3) search for a tool for eculizumab titration. An abnormal circulating complement profile (low C3, high C5a, or SC5b-9) was found in 47% to 64% of patients, irrespective of disease phase. Acute aHUS serum, but not serum from remission, caused wider C3 and C5b-9 deposits than control serum on unstimulated human microvascular endotheli…

Eliminating Factor H-Binding Activity of Borrelia burgdorferi CspZ Combined with Virus-Like Particle Conjugation Enhances Its Efficacy as a Lyme Dise…

2018

The spirochete Borrelia burgdorferi is the causative agent of Lyme disease, the most common tick-borne disease in the U.S and Europe. No potent human vaccine is currently available. The innate immune complement system is vital to host defense against pathogens, as complement activation on the surface of spirochetes results in bacterial killing. Complement system is inhibited by the complement regulator factor H. To escape killing, B. burgdorferi produces an outer surface protein CspZ that binds factor H to inhibit complement activation on the cell surface. Immunization with CspZ alone does not protect mice from infection, which we speculate is because factor H-binding cloaks potentially pro…

Research on complement: old issues revisited and a novel sphere of influence

2003

Immunology in recent years has taken a somewhat surprising turn, expressed by a renewed interest in innate immunity. Especially intriguing is the regulatory role exerted by the innate components on the adaptive response, with Toll receptors and complement components being the most investigated. This function has been firmly established for complement protein CR2 (CD21) as part of the BCR co-receptor CD19/CD21/CD81. New findings are now providing a broader picture of complement and its tuning of the immune response; for example, complement proteins have been implicated in the control of T-cell-mediated responses. We will review some of these data here and summarize new discoveries in areas o…

Notch signalling is off and is uncoupled from HES1 expression in Ewing's sarcoma

2010

Notch can act as an oncogene or as a tumour suppressor and thus can either promote or inhibit tumour cell growth. To establish Notch status in Ewing's sarcoma family of tumours (ESFT), we investigated the Notch pathway by gene expression profiling meta-analysis or immunohistochemistry in samples obtained from 96 and 24 ESFT patients, respectively. We found that although Notch receptors were highly expressed, Notch did not appear to be active, as evidenced by the absence of Notch receptors in cell nuclei. In contrast, we show that Notch receptors known to be active in colon adenocarcinoma, hepatocarcinoma, and pancreatic carcinoma stain cell nuclei in these tumours. High expression of the No…

La integración del factor humano en el ámbito técnico de la gestión de las carreteras y la seguridad vial: Un enfoque investigativo

2016

La tesis titulada “LA INTEGRACIÓN DEL FACTOR HUMANO EN EL ÁMBITO TÉCNICO DE LA GESTIÓN DE LAS CARRETERAS Y LA SEGURIDAD VIAL: UN ENFOQUE INVESTIGATIVO” tiene por objeto realizar una primera aproximación a la integración del factor humano en el ámbito técnico de la seguridad y gestión de la carretera. La investigación tiene un alcance novedoso. Y constituye un ejemplo de la necesaria aproximación y complementariedad entre disciplinas interrelacionadas unidas en un camino común el de la seguridad vial, como son la psicología y la ingeniería civil. Se tratan una serie de materias de vital importancia como los tópicos, estudios, metodologías y medidas relativas a la seguridad vial en la gestión…

Determinación de las variables de accidentalidad ferroviaria en las que interviene el factor humano: valoración del riesgo en los colectivos que son …

2013

El objetivo general de la tesis es determinar las variables de accidentalidad ferroviaria en las que interviene el factor humano y su valoración respecto los colectivos de riesgo del sistema ferroviario español. Para ello se han analizado los registros de accidentalidad del ferrocarril español, a excepción del Ferrocarril Español de Vía Estrecha (FEVE), para su descomposición en cadenas de sucesos, registrando cada uno de los sucesos en una base de datos estadística diseñada para este fin. Analizando los primeros eventos de la cadena de sucesos de los accidentes se han determinado las principales variables en las que interviene el factor humano, y mediante la base de datos de sucesos elabor…

Complement Receptor Analogous Factors in Human Serum: I. Isolation of a Molecule Inhibitory for Complement Dependent Rosette Formation, its Identific…

1979

Abstract A glycoprotein was isolated from human plasma which partially inhibited C3 carrying erythrocytes from binding to complement receptor cells (CR + C). Based on its physicochemical characteristics and its antigenicity this glycoprotein was identified as aI-antitrypsin (α 1 -AT). The activity of α 1 -AT towards-C3 and its fragments was unaffected by heating but it was destroyed by periodic acid. The isolated carbohydrate moiety of α 1 -AT showed the same effect as the intact molecule. Using F(ab) 2 of IgG-anti-α 1 -AT, α 1 -AT could be demonstrated on Raji cells and human erythrocytes. Treatment of these CR + C with IgG-anti-α 1 -AT resulted in a blockade of their C3 receptor activity.…