Gabriela Garcia - Academia.edu (original) (raw)

Papers by Gabriela Garcia

The FASEB Journal, 2008

In immune-induced inflammation, leukocytes are key mediators of tissue damage. Since A 2A adenosi... more In immune-induced inflammation, leukocytes are key mediators of tissue damage. Since A 2A adenosine receptors (A 2A Rs) are endogenous suppressors of inflammation, we examined cellular and molecular mechanisms of kidney damage to determine if selective activation of A 2A R would suppress inflammation in a rat model of glomerulonephritis. Activation of A 2A R reduced the degree of kidney injury in both the acute inflammatory phase and the progressive phase of glomerulonephritis. This protection against acute and chronic inflammation was associated with suppression of the glomerular expression of the MDC/CCL22 chemokine and down-regulation of MIP-1␣/CCL3, RANTES/CCL5, MIP-1␤/CCL4, and MCP-1/CCL2 chemokines. The expression of anti-inflammatory cytokines, interluekin (IL)-4 and IL-10, also increased. The mechanism for these anti-inflammatory responses to the A 2A R agonist was suppression of macrophages function. A 2A R expression was increased in macrophages, macrophage-derived chemokines were reduced in response to the A 2A R agonist, and chemokines not expressed in macrophages did not respond to A 2A R activation. Thus, activation of the A 2A R on macrophages inhibits immune-associated inflammation. In glomerulonephritis, A 2A R activation modulates inflammation and tissue damage even in the progressive phase of glomerulonephritis. Accordingly, pharmacological activation of A 2A R could be developed into a novel treatment for glomerulonephritis and other macrophage-related inflammatory diseases.

Computer Methods and Programs in Biomedicine, 2003

A number of methods for temporal alignment, feature extraction, and clustering of electrocardiogr... more A number of methods for temporal alignment, feature extraction, and clustering of electrocardiographic signals are proposed. The ultimate aim of the paper is to find a method to automatically reduce the quantity of beats to examine in a long-term electrocardiographic signal, known as Holter signal, without loss of valuable information for the diagnosis. These signals include thousands of beats, and therefore, visual inspection is difficult and cumbersome.

Hydrogeology Journal, 2001

The Salí River hydrogeological basin is one of the most productive artesian basins in Argentina. ... more The Salí River hydrogeological basin is one of the most productive artesian basins in Argentina. It is located in the southeastern part of the province of Tucumán, northwestern Argentina, and its groundwater resources are developed for water supply and irrigation. The chemical composition of the water is strongly influenced by the interaction with the basinal sediments and by hydrologic characteristics such as the flow pattern and time of residence. Three hydrochemical zones are defined in the study area and the processes that control the chemical composition of the water are manifestly different in each zone. The dissolution of halite, sodium sulphate, and gypsum explains part of the contained Na+, K+, Cl–, SO42–, and Ca2+, but other processes, such as cation exchange, calcite precipitation, weathering of aluminosilicates, and gas exchange with the atmosphere, also contribute to the water composition. The assessment of contamination indicators, such as pH, dissolved organic matter, dissolved oxygen, phosphate, and nitrate, indicates that the groundwater is suitable for human consumption. However, biological contamination has been detected in samples from some wells, especially those near the Salí River. Le bassin hydrogéologique de la rivière Salí est l'un des bassins artésiens les plus productifs d'Argentine. Il est situé dans la partie sud-est de la province de Tucumán, dans le nord-ouest de l'Argentine, et ses ressources en eaux souterraines sont exploitées pour l'alimentation en eau potable et pour l'irrigation. La composition chimique des eaux est fortement influencée par les interactions avec les sédiments du bassin et par les caractéristiques hydrologiques telles que les conditions d'écoulement et le temps de séjour. Trois zones hydrochimiques sont définies dans la région étudiée et les processus qui contrôlent la composition chimique des eaux sont manifestement différents d'une zone à l'autre. La dissolution de la halite, du sulfate de sodium et du gypse explique une partie des concentrations en Na+, K+, Cl–, SO42– et Ca2+, mais d'autres processus tels que l'échange de cations, la précipitation de calcite, l'altération d'aluminosilicates et des échanges gazeux avec l'atmosphère contribuent également à la composition chimique de l'eau. L'évaluation des indicateurs de contamination tels que le pH, la matière organique dissoute, l'oxygène dissous, les phosphates et les nitrates indique que l'eau souterraine convient bien à la consommation humaine. Toutefois, une contamination biologique a été détectée dans des échantillons provenant de certains puits, en particulier ceux proches de la rivière Salí. La cuenca hidrogeológica del Río Salí se encuentra ubicada en el extremo SE de la Provincia de Tucumán, Noroeste de Argentina, y constituye una de las cuencas hidrogeológicas más importantes del país. Sus recursos son intensamente explotados para el abastecimiento de agua potable y para riego. La composición química de estas aguas está fuertemente influida por su interacción con los sedimentos y por algunas características hidrogeológicas tales como velocidad de infiltración, patrones de flujo y tiempo de residencia en el acuífero. En el área de estudio se pudieron distinguir tres zonas hidroquímicas, en cada una de las cuales los procesos que controlan la composición química del agua se manifiestan en forma diferente. Entre los procesos identificados, la disolución de halita, de sulfatos de sodio y de yeso, explica en parte los contenidos observados de Na+, K+, Cl–, SO42– y Ca2+. También participan en la regulación de la composición del agua otros procesos, como el intercambio catiónico, la precipitación de calcita, la meteorización de aluminosilicatos y el intercambio gaseoso con la atmósfera. De acuerdo con los indicadores de contaminación analizados (pH, materia orgánica disuelta, oxígeno disuelto, fosfato y nitrato), estas aguas son aptas para consumo. Sin embargo, algunos pozos próximos al Río Salí presentan contaminación bacteriológica.

Journal of Clinical Investigation, 1995

Reactive oxygen intermediates (ROIs) play an important role in inflammatory processes as mediator... more Reactive oxygen intermediates (ROIs) play an important role in inflammatory processes as mediators of injury and potentially in signal transduction leading to gene expression. Cyclooxygenase (COX) is a rate-limiting enzyme in prostanoid biosynthesis, and its recently cloned inducible form, COX-2, is induced by proinflammatory cytokines. This study linked ROIs to the signaling pathways that induce COX-2 expression. The hydroxyl radical scavengers DMSO (1%), as well as di- and tetramethylthiourea, inhibited IL-1-, TNF alpha-, and LPS-induced COX-2 expression in rat mesangial cells. The suppression of COX-2 mRNA expression correlated with the COX-2 protein level. In comparison with the prolonged induction of the inducible gene encoding protein-tyrosine phosphatase by hydrogen peroxide, the COX-2 gene was only transiently induced. Protein-tyrosine phosphatase is also induced by heat shock and chemical stress, whereas COX-2 is not. Superoxide was a more potent inducer for COX-2 than hydrogen peroxide. In addition, NADPH stimulated COX-2 expression, and an inhibitor of NADPH oxidase blocked COX-2 expression induced by TNF alpha. COX-2 and KC gene expression costimulated by IL-1 were inhibited differentially by the scavengers. These studies demonstrate that oxidant stress is a specific and important inducer of COX-2 gene expression. This induction may contribute to the deleterious amplification of prostanoids in inflammation and compound the direct effects of ROI production.

Febs Letters, 1996

A full-length cDNA for rat 92-kDa type IV collagenase was isolated and sequenced. RNase protectio... more A full-length cDNA for rat 92-kDa type IV collagenase was isolated and sequenced. RNase protection assay revealed tissue specific differential expression of the 92-kDa type IV collagenase in the rat during development. Natural and modified forms of the 92-kDa type IV collagenase were expressed. One active protein, 92-CD, contained only the putative catalytic domain. Large quantities of the 92-CD were expressed in Escherichia coli, extracted from inclusion bodies, purified, and refolded to an active form. This recombinant protein was able to cleave denatured and native collagen and was inactivated by known MMP inhibitors.

Fractalkine is an endothelial cell-derived CX 3 C chemokine that is chemotactic mainly to mononuc... more Fractalkine is an endothelial cell-derived CX 3 C chemokine that is chemotactic mainly to mononuclear cells. Fractalkine was induced in rat aortic endothelial cells (RAEC) by interleukin-1␤ (IL-1␤), tumor necrosis factor ␣ (TNF-␣), and lipopolysaccharide (LPS) transcriptionally and translationally. This induction correlated with increased NF-B DNA binding activity as determined by gel mobility shift assay. Supershift assays revealed that the NF-B subunits p50 and p65 were responsible for B binding. Accordingly, we examined the role of NF-B in fractalkine induction in RAEC through the use of an adenovirus-mediated mutant IB as a specific inhibitor. Delivery of a dominant-negative form of IB␣ in RAEC dramatically reduced the induction of fractalkine by these stimuli, suggesting a role for NF-B activation in fractalkine induction. The inhibition of fractalkine expression by two potent NF-B inhibitors, sulfasalazine and sanguinarine, further supported the central role of NF-B in fractalkine transcription regulation and suggested a novel therapeutic target aimed at modulating leukocyte endothelial cell interaction.

American Journal of Pathology, 2003

Glomerular monocyte/macrophage (Mo/M phi) infiltrates play a role in many forms of glomerulonephr... more Glomerular monocyte/macrophage (Mo/M phi) infiltrates play a role in many forms of glomerulonephritis (GN), and the intensity of Mo/M phi trafficking correlates with the loss of renal function and histological damage. We analyzed the functional role of macrophage-derived chemokine (MDC), a potent mononuclear cell chemoattractant, during the progression of anti-glomerular basement membrane (GBM) antibody (Ab) GN, a model of crescentic GN in the WKY rat, and whether the effects of MDC were dependent on its receptor CCR4. MDC mRNA and protein expression were markedly induced in nephritic glomeruli throughout the disease. Blocking the function of MDC did not affect the developing of the disease from days 2 to 7, but it dramatically blocked M omicron/M phi infiltration in the glomeruli, prevented crescent formation, and reversed renal function impairment during days 7 to 14 of the anti-GBM GN. In this study, we also found that MDC activity on M omicron/M phi in this GN was at least partly dependent on a new variant of CCR4. These results suggest that MDC is critically involved in the development of anti-GBM GN from acute glomerular injury to irreversible tissue damage. In addition, an antagonist to MDC may represent a prime drug target for therapeutic application to intervene in the progression of anti-GBM GN and in other M omicron/M phi-dominant GN.

Kidney International, 1999

Prevention of crescentic glomerulonephritis by immunoneuof leukocytes from the blood stream into ... more Prevention of crescentic glomerulonephritis by immunoneuof leukocytes from the blood stream into tissues requires tralization of the fractalkine receptor CX 3 CR1. both the mechanisms for the leukocytes to slow down Background. Fractalkine is a newly identified T-cell and and adhere to the vascular endothelium and the display monocyte/macrophage (Mφ) chemokine with a transmembrane of recruiting signals at sufficient levels at the vicinity of domain and is a cell-surface protein on activated endothelium. the intended exit site. The exit of leukocytes would be

Chemokines play a central role in immune and inflammatory responses. It has been observed recentl... more Chemokines play a central role in immune and inflammatory responses. It has been observed recently that certain viruses have evolved molecular piracy and mimicry mechanisms by encoding and synthesizing proteins that interfere with the normal host defense response. One such viral protein, vMIP-II, encoded by human herpesvirus 8, has been identified with in vitro antagonistic activities against CC and CXC chemokine receptors. We report here that vMIP-II has additional antagonistic activity against CX 3 CR1, the receptor for fractalkine. To investigate the potential therapeutic effect of this broad-spectrum chemokine antagonist, we studied the antiinflammatory activity of vMIP-II in a rat model of experimental glomerulonephritis induced by an antiglomerular basement membrane antibody. vMIP-II potently inhibited monocyte chemoattractant protein 1-, macrophage inflammatory protein 1 ␤ -, RANTES (regulated on activation, normal T cell expressed and secreted)-, and fractalkine-induced chemotaxis of activated leukocytes isolated from nephritic glomeruli, significantly reduced leukocyte infiltration to the glomeruli, and markedly attenuated proteinuria. These results suggest that molecules encoded by some viruses may serve as useful templates for the development of antiinflammatory compounds.

En el marco de la Jornada de Educación Médica, realizada en la Facultad de Ciencias Médicas de la... more En el marco de la Jornada de Educación Médica, realizada en la Facultad de Ciencias Médicas de la UNLP, el 29 de junio próximo pasado, se desarrolló el Taller de DISEÑO CURRICULAR POR COMPETENCIAS con la participación de docentes de distintas cátedras de la carrera de Medicina.

The FASEB Journal, 2008

In immune-induced inflammation, leukocytes are key mediators of tissue damage. Since A 2A adenosi... more In immune-induced inflammation, leukocytes are key mediators of tissue damage. Since A 2A adenosine receptors (A 2A Rs) are endogenous suppressors of inflammation, we examined cellular and molecular mechanisms of kidney damage to determine if selective activation of A 2A R would suppress inflammation in a rat model of glomerulonephritis. Activation of A 2A R reduced the degree of kidney injury in both the acute inflammatory phase and the progressive phase of glomerulonephritis. This protection against acute and chronic inflammation was associated with suppression of the glomerular expression of the MDC/CCL22 chemokine and down-regulation of MIP-1␣/CCL3, RANTES/CCL5, MIP-1␤/CCL4, and MCP-1/CCL2 chemokines. The expression of anti-inflammatory cytokines, interluekin (IL)-4 and IL-10, also increased. The mechanism for these anti-inflammatory responses to the A 2A R agonist was suppression of macrophages function. A 2A R expression was increased in macrophages, macrophage-derived chemokines were reduced in response to the A 2A R agonist, and chemokines not expressed in macrophages did not respond to A 2A R activation. Thus, activation of the A 2A R on macrophages inhibits immune-associated inflammation. In glomerulonephritis, A 2A R activation modulates inflammation and tissue damage even in the progressive phase of glomerulonephritis. Accordingly, pharmacological activation of A 2A R could be developed into a novel treatment for glomerulonephritis and other macrophage-related inflammatory diseases.

Computer Methods and Programs in Biomedicine, 2003

A number of methods for temporal alignment, feature extraction, and clustering of electrocardiogr... more A number of methods for temporal alignment, feature extraction, and clustering of electrocardiographic signals are proposed. The ultimate aim of the paper is to find a method to automatically reduce the quantity of beats to examine in a long-term electrocardiographic signal, known as Holter signal, without loss of valuable information for the diagnosis. These signals include thousands of beats, and therefore, visual inspection is difficult and cumbersome.

Hydrogeology Journal, 2001

The Salí River hydrogeological basin is one of the most productive artesian basins in Argentina. ... more The Salí River hydrogeological basin is one of the most productive artesian basins in Argentina. It is located in the southeastern part of the province of Tucumán, northwestern Argentina, and its groundwater resources are developed for water supply and irrigation. The chemical composition of the water is strongly influenced by the interaction with the basinal sediments and by hydrologic characteristics such as the flow pattern and time of residence. Three hydrochemical zones are defined in the study area and the processes that control the chemical composition of the water are manifestly different in each zone. The dissolution of halite, sodium sulphate, and gypsum explains part of the contained Na+, K+, Cl–, SO42–, and Ca2+, but other processes, such as cation exchange, calcite precipitation, weathering of aluminosilicates, and gas exchange with the atmosphere, also contribute to the water composition. The assessment of contamination indicators, such as pH, dissolved organic matter, dissolved oxygen, phosphate, and nitrate, indicates that the groundwater is suitable for human consumption. However, biological contamination has been detected in samples from some wells, especially those near the Salí River. Le bassin hydrogéologique de la rivière Salí est l'un des bassins artésiens les plus productifs d'Argentine. Il est situé dans la partie sud-est de la province de Tucumán, dans le nord-ouest de l'Argentine, et ses ressources en eaux souterraines sont exploitées pour l'alimentation en eau potable et pour l'irrigation. La composition chimique des eaux est fortement influencée par les interactions avec les sédiments du bassin et par les caractéristiques hydrologiques telles que les conditions d'écoulement et le temps de séjour. Trois zones hydrochimiques sont définies dans la région étudiée et les processus qui contrôlent la composition chimique des eaux sont manifestement différents d'une zone à l'autre. La dissolution de la halite, du sulfate de sodium et du gypse explique une partie des concentrations en Na+, K+, Cl–, SO42– et Ca2+, mais d'autres processus tels que l'échange de cations, la précipitation de calcite, l'altération d'aluminosilicates et des échanges gazeux avec l'atmosphère contribuent également à la composition chimique de l'eau. L'évaluation des indicateurs de contamination tels que le pH, la matière organique dissoute, l'oxygène dissous, les phosphates et les nitrates indique que l'eau souterraine convient bien à la consommation humaine. Toutefois, une contamination biologique a été détectée dans des échantillons provenant de certains puits, en particulier ceux proches de la rivière Salí. La cuenca hidrogeológica del Río Salí se encuentra ubicada en el extremo SE de la Provincia de Tucumán, Noroeste de Argentina, y constituye una de las cuencas hidrogeológicas más importantes del país. Sus recursos son intensamente explotados para el abastecimiento de agua potable y para riego. La composición química de estas aguas está fuertemente influida por su interacción con los sedimentos y por algunas características hidrogeológicas tales como velocidad de infiltración, patrones de flujo y tiempo de residencia en el acuífero. En el área de estudio se pudieron distinguir tres zonas hidroquímicas, en cada una de las cuales los procesos que controlan la composición química del agua se manifiestan en forma diferente. Entre los procesos identificados, la disolución de halita, de sulfatos de sodio y de yeso, explica en parte los contenidos observados de Na+, K+, Cl–, SO42– y Ca2+. También participan en la regulación de la composición del agua otros procesos, como el intercambio catiónico, la precipitación de calcita, la meteorización de aluminosilicatos y el intercambio gaseoso con la atmósfera. De acuerdo con los indicadores de contaminación analizados (pH, materia orgánica disuelta, oxígeno disuelto, fosfato y nitrato), estas aguas son aptas para consumo. Sin embargo, algunos pozos próximos al Río Salí presentan contaminación bacteriológica.

Journal of Clinical Investigation, 1995

Reactive oxygen intermediates (ROIs) play an important role in inflammatory processes as mediator... more Reactive oxygen intermediates (ROIs) play an important role in inflammatory processes as mediators of injury and potentially in signal transduction leading to gene expression. Cyclooxygenase (COX) is a rate-limiting enzyme in prostanoid biosynthesis, and its recently cloned inducible form, COX-2, is induced by proinflammatory cytokines. This study linked ROIs to the signaling pathways that induce COX-2 expression. The hydroxyl radical scavengers DMSO (1%), as well as di- and tetramethylthiourea, inhibited IL-1-, TNF alpha-, and LPS-induced COX-2 expression in rat mesangial cells. The suppression of COX-2 mRNA expression correlated with the COX-2 protein level. In comparison with the prolonged induction of the inducible gene encoding protein-tyrosine phosphatase by hydrogen peroxide, the COX-2 gene was only transiently induced. Protein-tyrosine phosphatase is also induced by heat shock and chemical stress, whereas COX-2 is not. Superoxide was a more potent inducer for COX-2 than hydrogen peroxide. In addition, NADPH stimulated COX-2 expression, and an inhibitor of NADPH oxidase blocked COX-2 expression induced by TNF alpha. COX-2 and KC gene expression costimulated by IL-1 were inhibited differentially by the scavengers. These studies demonstrate that oxidant stress is a specific and important inducer of COX-2 gene expression. This induction may contribute to the deleterious amplification of prostanoids in inflammation and compound the direct effects of ROI production.

Febs Letters, 1996

A full-length cDNA for rat 92-kDa type IV collagenase was isolated and sequenced. RNase protectio... more A full-length cDNA for rat 92-kDa type IV collagenase was isolated and sequenced. RNase protection assay revealed tissue specific differential expression of the 92-kDa type IV collagenase in the rat during development. Natural and modified forms of the 92-kDa type IV collagenase were expressed. One active protein, 92-CD, contained only the putative catalytic domain. Large quantities of the 92-CD were expressed in Escherichia coli, extracted from inclusion bodies, purified, and refolded to an active form. This recombinant protein was able to cleave denatured and native collagen and was inactivated by known MMP inhibitors.

Fractalkine is an endothelial cell-derived CX 3 C chemokine that is chemotactic mainly to mononuc... more Fractalkine is an endothelial cell-derived CX 3 C chemokine that is chemotactic mainly to mononuclear cells. Fractalkine was induced in rat aortic endothelial cells (RAEC) by interleukin-1␤ (IL-1␤), tumor necrosis factor ␣ (TNF-␣), and lipopolysaccharide (LPS) transcriptionally and translationally. This induction correlated with increased NF-B DNA binding activity as determined by gel mobility shift assay. Supershift assays revealed that the NF-B subunits p50 and p65 were responsible for B binding. Accordingly, we examined the role of NF-B in fractalkine induction in RAEC through the use of an adenovirus-mediated mutant IB as a specific inhibitor. Delivery of a dominant-negative form of IB␣ in RAEC dramatically reduced the induction of fractalkine by these stimuli, suggesting a role for NF-B activation in fractalkine induction. The inhibition of fractalkine expression by two potent NF-B inhibitors, sulfasalazine and sanguinarine, further supported the central role of NF-B in fractalkine transcription regulation and suggested a novel therapeutic target aimed at modulating leukocyte endothelial cell interaction.

American Journal of Pathology, 2003

Glomerular monocyte/macrophage (Mo/M phi) infiltrates play a role in many forms of glomerulonephr... more Glomerular monocyte/macrophage (Mo/M phi) infiltrates play a role in many forms of glomerulonephritis (GN), and the intensity of Mo/M phi trafficking correlates with the loss of renal function and histological damage. We analyzed the functional role of macrophage-derived chemokine (MDC), a potent mononuclear cell chemoattractant, during the progression of anti-glomerular basement membrane (GBM) antibody (Ab) GN, a model of crescentic GN in the WKY rat, and whether the effects of MDC were dependent on its receptor CCR4. MDC mRNA and protein expression were markedly induced in nephritic glomeruli throughout the disease. Blocking the function of MDC did not affect the developing of the disease from days 2 to 7, but it dramatically blocked M omicron/M phi infiltration in the glomeruli, prevented crescent formation, and reversed renal function impairment during days 7 to 14 of the anti-GBM GN. In this study, we also found that MDC activity on M omicron/M phi in this GN was at least partly dependent on a new variant of CCR4. These results suggest that MDC is critically involved in the development of anti-GBM GN from acute glomerular injury to irreversible tissue damage. In addition, an antagonist to MDC may represent a prime drug target for therapeutic application to intervene in the progression of anti-GBM GN and in other M omicron/M phi-dominant GN.

Kidney International, 1999

Prevention of crescentic glomerulonephritis by immunoneuof leukocytes from the blood stream into ... more Prevention of crescentic glomerulonephritis by immunoneuof leukocytes from the blood stream into tissues requires tralization of the fractalkine receptor CX 3 CR1. both the mechanisms for the leukocytes to slow down Background. Fractalkine is a newly identified T-cell and and adhere to the vascular endothelium and the display monocyte/macrophage (Mφ) chemokine with a transmembrane of recruiting signals at sufficient levels at the vicinity of domain and is a cell-surface protein on activated endothelium. the intended exit site. The exit of leukocytes would be

Chemokines play a central role in immune and inflammatory responses. It has been observed recentl... more Chemokines play a central role in immune and inflammatory responses. It has been observed recently that certain viruses have evolved molecular piracy and mimicry mechanisms by encoding and synthesizing proteins that interfere with the normal host defense response. One such viral protein, vMIP-II, encoded by human herpesvirus 8, has been identified with in vitro antagonistic activities against CC and CXC chemokine receptors. We report here that vMIP-II has additional antagonistic activity against CX 3 CR1, the receptor for fractalkine. To investigate the potential therapeutic effect of this broad-spectrum chemokine antagonist, we studied the antiinflammatory activity of vMIP-II in a rat model of experimental glomerulonephritis induced by an antiglomerular basement membrane antibody. vMIP-II potently inhibited monocyte chemoattractant protein 1-, macrophage inflammatory protein 1 ␤ -, RANTES (regulated on activation, normal T cell expressed and secreted)-, and fractalkine-induced chemotaxis of activated leukocytes isolated from nephritic glomeruli, significantly reduced leukocyte infiltration to the glomeruli, and markedly attenuated proteinuria. These results suggest that molecules encoded by some viruses may serve as useful templates for the development of antiinflammatory compounds.

En el marco de la Jornada de Educación Médica, realizada en la Facultad de Ciencias Médicas de la... more En el marco de la Jornada de Educación Médica, realizada en la Facultad de Ciencias Médicas de la UNLP, el 29 de junio próximo pasado, se desarrolló el Taller de DISEÑO CURRICULAR POR COMPETENCIAS con la participación de docentes de distintas cátedras de la carrera de Medicina.