Browsing by Author "Soza, A"

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    Antibodies 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, A
    Background: 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).
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    Galectin-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, A
    Integrin-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.
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    Histological resolution of steatohepatitis after iron depletion
    (2004) Riquelme, A; Soza, A; Nazal, L; Martínez, G; Kolbach, M; Patillo, A; Arellano, M; Duarte, I; Martínez, J; Molgó, M; Arrese, M
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    Increased orocecal transit time in patients with nonalcoholic fatty liver disease
    (2005) Soza, A; Riquelme, A; González, R; Alvarez, M; Pérez-Ayuso, RM; Glasinovic, JC; Arrese, M
    Intestinal bacterial overgrowth (IBO) has been suggested to play a pathogenic role in patients with nonalcoholic fatty liver disease (NAFLD). Delayed intestinal transit may contribute to IBO development. Ten nondiabetic patients with NAFLD and abnormal liver enzymes were recruited. Ten healthy individuals, matched by sex, age, and body mass index, were used as controls. Orocecal transit time (OCTT) was measured by the lactulose breath test. Anti-endotoxin core antibodies (EndoCAb) were determined. The effect of oral norfloxacin (400 mg BID during 2 weeks) on liver enzymes, lactulose breath test, and EndoCAb was also studied. NAFLD patients had higher basal breathed H, and prolonged OCTT compared to controls (127 +/- 61 vs. 57 +/- 23 min, respectively; P=0.0037). EndoCAb titers were similar in NAFLD patients and controls. Norfloxacin administration had no effect on ALT levels, lactulose breath test, or EndoCAb titers in patients with NAFLD. The present data show evidence of deranged intestinal motility in nondiabetic patients with NAFLD and support the hypothesis that NAFLD could be linked to endotoxin-induced liver damage of intestinal origin.
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    Predictors of nonalcoholic steatohepatitis (NASH) in obese patients undergoing gastric bypass
    (2005) Boza, C; Riquelme, A; Ibañez, L; Duarte, I; Norero, E; Viviani, P; Soza, A; Fernandez, JI; Raddatz, A; Guzman, S; Arrese, M
    Background: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are conditions gaining increasing recognition in hepatology as a potential cause of cirrhosis and end-stage liver disease. Obesity is one of the main risk factors. The aims of this study were to determine the frequency of NAFLD in obese patients and to identify variables that predict NASH.
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    Sorting competition with membrane-permeable peptides in intact epithelial cells revealed discrimination of transmembrane proteins not only at the trans-Golgi network but also at pre-Golgi stages
    (2004) Soza, A; Norambuena, A; Cancino, J; de la Fuente, E; Henklein, P; González, A
    Transmembrane proteins destined to the basolateral cell surface of epithelial cells contain in their cytosolic domain at least two classes of sorting signals: one class promotes exit from the endoplasmic reticulum (ER) and transport to the Golgi complex, and the other class operates at the trans-Golgi network (TGN) specifying segregation into basolateral exocytic pathways. Both kinds of addressing motifs are quite diverse among different proteins. It is unclear to what extent this feature reflects alternative decoding mechanisms or variations in motifs recognized by the same sorting factor. Here we applied a novel strategy based on permeable peptide technology and temperature-sensitive model proteins to study competition between cytosolic sorting motifs in the context of mammalian living cells. We used the transduction domain of HIV-1 Tat protein to make a membrane-permeable peptide of the cytosolic tail of GtsO45, which contains a well characterized ER exit di-acidic (DIE) motif and a tyrosine-based basolateral sorting signal (YTDI). This peptide added to the media inhibited transport of GtsO45 from both ER-to-Golgi and TGN-to-basolateral cell surface in transfected Madin-Darby canine kidney cells. Instead, it did not affect the exocytic trafficking of a GtsO45-derived chimeric protein bearing 30 juxtamembrane residues from the cytosolic domain of the epidermal growth factor receptor that contains a variant ER exit motif (ERE) and an unconventional proline-based basolateral sorting signal. These results not only proved the feasibility of competing for sorting events in intact cells but also showed that distinct plasma membrane proteins can be discriminated at pre-TGN stages, and that basolateral sorting involves different recognition elements for tyrosine-based motifs and an unconventional basolateral motif.
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    Successful liver transplantation and delivery in a woman with fulminant hepatic failure occurring during the second trimester of pregnancy
    (WILEY, 2006) Jarufe, N; Soza, A; Perez Ayuso, RM; Poblete, JA; Gonzalez, R; Guajardo, M; Hernandez, V; Riquelme, A; Arrese, M; Martinez, J
    Background: Severe liver dysfunction occurring during pregnancy is an unusual but dramatic event that poses special technical and ethical issues because it involves two lives. Methods an Results: We report the case of a 35-year-old woman with cryptogenic fulminant hepatic failure who underwent successful orthotopic liver transplantation at 22 weeks of pregnancy. After a relatively uneventful post-operative course she delivered a normal offspring at the 27th week of gestation. There were no obstetrical complications and neonatal outcome was excellent. After a year of follow-up, the patient is doing well,and the newborn has exhibited normal psychomotor and weight/height development. Conclusions: This case illustrates the challenge of treating fulminant hepatic failure during pregnancy and demonstrates that liver transplantation is a feasible therapeutic option for treatment of patients with this condition, allowing successful completion of pregnancy.