Browsing by Author "Jacobelli, S"
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- ItemAntibodies against galectin-8 in patients with systemic lupus erythematosus(SOC MEDICA SANTIAGO, 2006) Pardo, E; Carcamo, C; Massardo, L; Mezzano, V; Jacobelli, S; Gonzalez, A; Soza, ABackground: The family of lectins known as galectins (galectins 1-14) are involved in the regulation of the immune system and in oncogenesis. During a search for antigens recognized by antibodies produced by a patient with systemic lupus erythematosus described. Aim: To determine the frequency of autoantibodies against galectin-8 in lupus patients compared with healthy controls. Patients and Methods: Galectin-8 was purified from a bacterial expression system and used in immunoblot assays as antigen to screen the sera of 55 SLE patients and matched controls. Disease activity was evaluated using the Mexican Modification of the Systemic Lupus Erythematosus Disease Activity Index (MEX-SLEDAI). Results: Reactivity against galectin-8 was detected in 30% of SLE patients, compared to 7% ofcontrols (p = 0.003). We could not detect any particular SLE manifestation associated to the pressence of these autoantibodies. Conclusion: This is the first description of autoantibodies against galectin-8. Its higher frequency in a patients with SLE suggests a pathogenic role. Further studies are needed to determine their clinical relevance (Rev Med Chile 2006; 134: 159-66).
- ItemCardiovascular risk factors in Chilean patients with rheumatoid arthritis(J RHEUMATOL PUBL CO, 2002) Cisternas, M; Gutierrez, MA; Klaassen, J; Acosta, AM; Jacobelli, SObjective. Epidemiologic studies have shown an increased mortality rate in patients with rheumatoid arthritis (RA). The most common cause of death in these patients is cardiovascular disease. We estimated the frequency of and examined risk factors for coronary artery disease in Chilean patients with RA.
- ItemCatastrophic antiphospholipid syndrome associated with crescentic glomerulonephritis(2000) Cisternas, M; Gutiérrez, MA; Rosenberg, H; Jara, A; Jacobelli, SThe association of renal failure with catastrophic antiphospholipid syndrome has been reported in the context of microvascular occlusions and/or malignant hypertension. We describe a 36-year-old woman who died of multiorgan failure with the laboratory, clinical and histopathological characteristics of catastrophic antiphospholipid syndrome associated with a crescentic glomerulonephritis and renal failure.
- ItemGalectin-8 binds specific beta 1 integrins and induces polarized spreading highlighted by asymmetric lamellipodia in Jurkat T cells(ELSEVIER INC, 2006) Carcamo, C; Pardo, E; Oyanadel, C; Bravo Zehnder, M; Bull, P; Caceres, M; Martinez, J; Massardo, L; Jacobelli, S; Gonzalez, A; Soza, AIntegrin-mediated encounters of T cells with extracellular cues lead these cells to adhere to a variety of substrates and acquire a spread phenotype needed for their tissue incursions. We studied the effects of galectin-8 (Gal-8), beta-galactoside binding lectin, on Jurkat T cells. Immobilized Gal-8 bound alpha 1 beta 1 and alpha 5 beta 1 but not alpha 2 beta 1 and alpha 4 beta 1 and adhered these cells with similar kinetics to immobilized fibronectin (FN). Function-blocking experiments with monoclonal anti-integrin antibodies suggested that alpha 5 beta 1 is the main mediator of cell adhesion to this lectin. Gal-8, but not FN, induced extensive cell spreading frequently leading to a polarized phenotype characterized by an asymmetric lamellipodial protrusion. These morphological changes involved actin cytoskeletal rearrangements controlled by PI3K, Rac-1 and ERK1/2 activity. Gal-8-induced Rac-1 activation and binding to alpha 1 and alpha 5 integrins have not been described in any other cellular system. Strikingly, Gal-8 was also a strong stimulus on Jurkat cells in suspension, triggering ERK1/2 activation that in most adherent cells is instead dependent on cell attachment. In addition, we found that patients with systemic lupus erythematosus (SLE), a prototypic autoimmune disorder, produce Gal-8 autoantibodies that impede both its binding to integrins and cell adhesion. These are the first function-blocking autoantibodies reported for a member of the galectin family. These results indicate that Gal-8 constitutes a novel extracellular stimulus for T cells, able to bind specific beta 1 integrins and to trigger signaling pathways conducive to cell spreading. Gal-8 could modulate a wide range of T cell-driven immune processes that eventually become altered in autoimmune disorders. (C) 2005 Elsevier Inc. All rights reserved.
- ItemHypothalamic-pituitary-adrenal axis function in patients with active rheumatoid arthritis(1999) Gutiérrez, MA; García, ME; Rodríguez, JA; Mardonez, G; Jacobelli, S; Rivero, SObjective. To study the response of cortisol and of prolactin (PRL) to specific stimuli in rheumatoid arthritis (RA).
- ItemLong-Term outcome of type V lupus membranous glomerulonephritis(SOC MEDICA SANTIAGO, 2005) Pasten, R; Massardo, L; Rosenberg, H; Radrigan, F; Roessler, E; Valdivieso, A; Jacobelli, SBackground: The long-term outcome of the pure form of WHO type V lupus membranous glomerulonephritis is apparently more benign than that of other forms of lupus glomerulonepbritis. However 12% of such patients progress to terminal renal failure. The presence of proteinuria may be an indication of cytotoxic agents. Aim: To study the clinical long-term outcome of WHO type V Inpus membranous glomerulonepbritis. Material and methods: A retrospective analysis of all kidney biopsies of a University Pathology Department, with the diagnosis of WHO type V lupus membranous glomerulonephritis. Review of medical records of patients with the disease and one clinical assessment of all living patients. Results: Between 1973 and 2000, 703 kidney biopsies were done to patients with systemic lupus erytbematosus. Of these, 40 were membranous glomerulonepbritis and in 33 patients (28 women, age range 6-71 years), data on the evolution and survival was obtained. Nineteen bad type Va and the rest type Vb nephritis. Two presented with renal failure and I I with proteinuria over 3.5 g/24h. The median follow-up since the renal biopsy was 63 months (range 1-316). At the end of follow-up, four bad a creatinine clearance of less then 15 ml/h and four a clearance between 15 and 29 ml/h (one of these received a renal allograft). Eleven (33016) patients had died, mostly due to infections. Life expectancy at five years with a creatinine clearance over 15 ml/h was 75%. Bad prognostic factors were an elevated creatinine clearance over 15 ml/h was 75%. Bad prognostic factors were an elevated creatinine and high blood pressure at the moment of the biopsy. Conclusions: The clinical outcome of these patients was bad. Twelve percent reached a stage of terminal renal failure. This is in contrast with the 3% progression to a similar stage of proliferalive glomerulonephritis treated with the 3% cycloposphamide. New tberapies for this condition must be sought.
- ItemLymphoid B cells induce NF-kappa B activation in high endothelial cells from human tonsils(OXFORD UNIV PRESS, 2006) Naves, R; Reyes, LI; Rosemblatt, M; Jacobelli, S; Gonzalez, A; Bono, MRImmune surveillance depends on still poorly understood lymphocyte-endothelium interactions required for lymphocyte transendothelial migration into secondary lymphoid organs. The nuclear factor kappa B (NF-kappa B) regulatory system and its inhibitory I kappa B proteins control the inducible expression of adhesion molecules, cytokines and chemokines involved in endothelial activation and lymphocyte transmigration. Here we present results showing the activation of this system in response to the interaction of high endothelial cells from human tonsils (HUTEC) with human B and T lymphoid cell lines and primary tonsillar lymphocytes. Western blot and electrophoretic mobility shift assays show that adhesion of different lymphoid cells induce varying levels of NF-kappa B activation in HUTEC, with Daudi cells, tonsil-derived B cell line 10 (TBCL-10) and primary tonsillar B lymphocytes causing the strongest activation. The main NF-kappa B protein complexes translocated to the nucleus were p65/p50 and p50/p50. Results from reverse transcription-PCR and flow cytometry analysis of HUTEC indicate that the interaction with Daudi cells induce an increased expression of IL-6 and IL-8 mRNA and cell-surface expression of intercellular adhesion molecule-1, all of which were prevented by sodium salicylate, an inhibitor of NF-kappa B activation. Transwell experiments show that NF-kappa B activation and the response of HUTEC to the interaction of Daudi cells does not depend on direct cell-cell contact but rather on the production of soluble factors that require the presence of both cell types. These results suggest that lymphocytes and high endothelium establish a cross talk leading to NF-kappa B-mediated expression of cytokines and adhesion molecules, inducing endothelial cell activation.
- ItemThe presence of the HLA-DRB1 shared epitope correlates with erosive disease in Chilean patients with rheumatoid arthritis(OXFORD UNIV PRESS, 2002) Massardo, L; Gareca, N; Cartes, MA; Cervilla, V; Gonzalez, A; Jacobelli, SObjective. To assess the contribution of the HLA-DRB1 shared epitope (SE) to the radiological outcome of rheumatoid arthritis (RA) after 6 yr of follow-up in a reported series of 129 Chilean patients with established disease.