Browsing by Author "Gonzalez, A"

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    11 beta-hydroxysteroid dehydrogenase activity in patients with hypertension and low plasma renin activity
    (2002) Mosso, L; Carvajal, C; Campino, C; Rojas, A; Gonzalez, A; Barraza, A; Montero, J; Fardella, C; NCD Risk Factor Collaboration (NCD-RisC)
    Background: Half of hypertensive patients with, low plasma renin activity have a primary hyperaldosteronism. Among the remaining half 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) deficiency plays all important role. This enzyme catalyzes the conversion of cortisol to cortisone, avoiding the interaction of cortisol with, the mineralocorticoid receptor. If the enzyme fails, cortisol will stimulate sodium and water reabsorption and increase blood pressure. Aim: To determine biochemical alterations, suggestive of 11betaSHSD2 deficiency, in low-renin hypertensive patients. Patients and Methods: Twenty eight hypertensive patients with a plasma renin activity of less than 0.5 ug/ml/h and with a plasma aldosterone of less than 5 ng/dl were studied. Twenty eight normotensive patients were studied as controls. Serum. cortisol (RIA), cortisone (ELISA) and the serum cortisol/cortisone ratio were determined in all of them, between, 9 and 10 AM. Measurements were confirmed by high pressure liquid chromatography. The serum cortisol/cortisone ratio was considered abnormal when its Ln (cortisol/cortisone) value was over 2 standard deviations of the mean. Results: Serum cortisol was higher in hypertensive subjects than in controls (11.1 +/- 3.3 and 9.2 +/- 2.8 mug/dl, respectively; p <0.05). No differences were observed in serum cortisone (3.4 +/- 1.3 and 3.7 +/- 1.2 μg/dl, respectively). Four hypertensive subjects bad all abnormally high Ln (cortisol/cortisone) value (1.86; 1.73; 2.07 and 2.01, considering a normal value of less than 1.61). Conclusions: Four of 28 hypertensive subjects with, low plasma renin activity and aldosterone had biochemical alterations suggestive of 11.1βHSD2 deficiency.
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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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    Cholesterol depletion induces PKA-mediated basolateral-to-apical transcytosis of the scavenger receptor class B type I in MDCK cells
    (NATL ACAD SCIENCES, 2004) Burgos, PV; Klattenhoff, C; de la Fuente, E; Rigotti, A; Gonzalez, A
    Cholesterol-based membrane microdomains, or lipid rafts, are believed to play important, yet poorly defined, roles in protein trafficking and signal transduction. In polarized epithelial cells, the current view is that rafts are involved in apical but not in basolateral protein transport from the trans-Golgi network (TGN). We report here that cholesterol is required in a post-TGN mechanism of basolateral regionalization. Permanently transfected Madin-Darby canine kidney cells segregated the caveolae/raft-associated high-density lipoprotein scavenger receptor class B type I (SR-BI) predominantly to the basolateral domain where it was constitutively internalized and recycled basolaterally. Acute cholesterol depletion did not significantly alter SR-BI internalization, implying a cholesterol depletion-insensitive endocytic process but instead induced its transcytosis through a protein kinase A (PKA)- and microtubule-dependent mechanism. Forskolin also elicited SR-BI transcytosis. The basolateral distribution of endogenous epidermal growth factor receptor remained unaffected. Strikingly, cholesterol depletion induced PKA activity without increasing the cAMP levels. Thus, our results are consistent with a scenario in which cholesterol-based rafts promote internalization and basolateral recycling of internalized SR-BI whereas a PKA pool sensitive to cholesterol depletion mediates SR-BI transcytosis. Regulated transcytosis of SR-BI may provide an additional mechanism to control cholesterol homeostasis. These results disclose relationships between cholesterol-based rafts and PKA activity operating in a post-TGN mechanism of regulated apical-to-basolateral cell surface protein distribution.
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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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    Glycans in post-Golgi apical targeting: sorting signals or structural props?
    (ELSEVIER SCIENCE LONDON, 1999) Rodriguez Boulan, E; Gonzalez, A
    A recent model proposed that N-glycans serve as apical targeting signals for soluble and membrane proteins in epithelial cells and neurons by interacting with lectin sorters in the trans-Golgi network. However, we believe that a number of experimental observations support an alternative hypothesis, that N-glycans play a facilitative role, by providing structural support or preventing aggregation of the proteins for example, thereby allowing interaction of proteinaceous apical sorting signals with the sorting machinery. This article discusses the experimental data currently available and how they relate to the proposed models.
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    Lymphoid 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, MR
    Immune 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.
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    Primary aldosteronism and hypertensive disease
    (2003) Mosso, L; Carvajal, C; Gonzalez, A; Barraza, A; Avila, F; Montero, J; Huete, A; Gederlini, A; Fardella, CE; NCD Risk Factor Collaboration (NCD-RisC)
    Recent studies in hypertensive populations that have used the serum aldosterone ( SA) to plasma renin activity (PRA) ratio as a screening test have demonstrated a high prevalence of primary aldosteronism (PA). This frequency is higher than that previously described when hypokalemia was used as a screening tool. However, other factors, such as the characteristics of hypertensive disease, could also influence the prevalence of PA. We studied 609 essential hypertensive patients, classified according to the Joint National Committee VI (JNC VI), in 3 different stages depending on the severity of their hypertensive disease. We measured SA and PRA and calculated the SA-PRA ratio for all patients. An SA-PRA ratio > 25 was detected in 63 of 609 patients, and the fludrocortisone test confirmed the PA diagnoses in 37 of 609 ( 6.1%) cases. PA prevalence according to hypertension stage was as follows: stage 1, 6 of 301 cases ( 1.99%); stage 2, 15 of 187 cases (8.02%); and stage 3, 16 of 121 cases (13.2%). PA patients were slightly younger than the other hypertensive patients ( 48.4 +/- 10.5 vs 53.6 +/- 10.2 years; P < 0.05). Serum potassium levels were normal in 36 of 37 PA patients; only 1 patient had minor hypokalemia. Computed tomography scans showed bilateral adrenal enlargement in 7 and an adrenal nodule in 2 cases. In summary, we found a high frequency of PA in essential hypertensives classified in stages 2 and 3 according to the JNC VI. The low frequency of computed tomography scan abnormalities and hypokalemia suggests that the diagnosis for most PA patients corresponds to attenuated forms of the disease.
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    The 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, S
    Objective. 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.