Anti-tumor necrosis factor-alpha therapy during murine Klebsiella pneumoniae bacteremia: increased mortality in the absence of liver injury.

Klebsiella pneumoniae is a leading cause of gram-negative bacterial pneumonia, often resulting in bacteremia concurrent with the localized pulmonary infection. The beneficial role of tumor necrosis factor (TNF)-alpha during pulmonary infection has been well documented; however, consequences of TNF-alpha production during systemic bacterial infection are controversial. A murine model of K. pneumoniae was developed to address this important issue. Liver-associated TNF-alpha mRNA was induced within 30 min after intravenous bacterial inoculation and remained elevated through 6 h before returning to near-baseline at 24 h postinfection. Intravenous K. pneumoniae infection induced liver cellular injury that was completely ablated when mice were pretreated with a neutralizing anti-TNF-alpha antibody. Interestingly, this reduction in liver injury failed to translate into improved survival. Mice receiving anti-TNF-alpha continued to succumb to the infection even out to day 10 postinfection. Bacterial clearance after TNF-alpha neutralization was significantly impaired at later time points during infection. Correlating with impaired bacterial clearance was diminished production of liver-associated MIP-2, MIP-1alpha, MCP-1, and interferon-gamma. Further evidence of diminished antibacterial immune responses was noted when the activational status of splenic natural killer cells in anti-TNF-alpha-treated mice was examined 24 h postinfection. Natural killer cells displayed decreased CD69 expression. Combined, these data indicate that the beneficial effects of TNF-alpha during systemic K. pneumoniae infection outweigh the detrimental effects of TNF-alpha-mediated hepatocyte cellular injury. Anti-TNF-alpha therapy, although preventing liver injury during blood-borne bacterial infection, results in a dampened anti-bacterial host response, resulting in decreased bacterial clearance and overall survival

Heavenly Venus: Mary Magdalene In Renaissance Noli Me Tangere Images

Mary Magdalene has fulfilled many roles since she was first mentioned in the New Testament. Some of the most popular characters she has played are as First Witness to Christ\u27s resurrection, follower and companion of Christ, Apostle to the Apostles, penitential whore, and exemplar for Christian women. This thesis was researched and written to explore some of these personae as they appear in Renaissance images of the Noli Me Tangere scene. The Noli Me Tangere story, which describes Christ\u27s post-resurrection appearance to Mary Magdalene, comes from the Gospel of John Chapter 20:12-15. Until the fourteenth century the Noli Me Tangere scene was depicted as a part of pictorial cycles concerning the life and death of Christ, or on rare occasions the life and death of the Magdalene herself. However, with an increasing interest in humanism, artists began to explore the Noli Me Tangere scene as an opportunity to analyze Christ\u27s humanity and sexuality. The Noli Me Tangere as a backdrop is ideal since Mary Magdalene already suffers a reputation as a wanton woman. Renaissance images of Mary Magdalene often depict the Magdalene as a Heavenly Venus. While the sensuality of Mary Magdalene as a licentious saint and the iconography of Venus as the representation of sexuality have been previously examined by scholars, the love aspect of Venus iconology as evident in the Noli Me Tangere images of the Magdalene has received little, if any, attention. As the foremost icon of reformed sinner, Mary Magdalene is representative of both lust and love, much like the goddess Venus, and several Renaissance images illustrate this dichotomy. The image of the Magdalene as both a symbol of lust and love relates to her dual nature as an ideal woman and a wanton woman. In Renaissance culture, two fundamental types of women existed, the good and the bad. Each type of woman was assigned a set of traits which would indicate her social standing. The ideal woman should be beautiful, chaste, and obedient while the wanton woman was promiscuous and independent. Due to her mistaken identity as a fallen woman, Mary Magdalene was on the one hand assumed to be a prostitute and is often portrayed with the attributes of a temptress; in addition, the Gospels describe the Magdalene as a woman with independent means. On the other hand, Mary Magdalene repented her evil ways and found faith in Jesus Christ. She was already a renowned beauty, and after her conversion, she became the model of chastity and obedience. Analyses of Mary Magdalene\u27s image in several Renaissance Noli Me Tangere paintings reflect both actual Renaissance women\u27s lives and the perception of Renaissance women. Thus, Mary Magdalene represents the dichotomy of woman as ideal and wanton; loving and lustful; forgiven and fallen; exemplary and immoral; chaste and seductive; obedient and willful; and lastly, saint and sinner

Increased Mortality and Dysregulated Cytokine Production in Tumor Necrosis Factor Receptor 1-Deficient Mice following Systemic Klebsiella pneumoniae Infection

A significant clinical complication of pulmonary infections with Klebsiella pneumoniae is peripheral blood dissemination, resulting in a systemic infection concurrent with the localized pulmonary infection. In this context, little is known about the role of tumor necrosis factor receptor 1 (TNFR1)-mediated innate immune responses during systemic Klebsiella infections. Mice lacking TNFR1 were significantly more susceptible to Klebsiella-induced mortality following intravenous inoculation. Bacterial clearance was impaired in TNFR1-deficient mice at early times following infection. Unexpectedly, bacterial burdens at the onset of mortality (days 2 to 3 postinfection) were not higher in mice lacking TNFR1. However, elevated production of liver-associated proinflammatory cytokines (interleukin-12, tumor necrosis factor alpha [TNF-α[, and gamma interferon [IFN-γ]) and chemokines (MIP-1α, MIP-2, and MCP-1) was observed within the first 24 h of infection. Additionally, excessive plasma-associated IFN-γ was also observed late in the course of infection (day 3). Spleen cells from day-3 infected TNFR1-deficient mice secreted markedly enhanced levels of IFN-γ when cultured in vitro. Additionally, there was a marked increase in the total number of activated lymphocyte subsets as indicated by CD69 upregulation. A notable exception was the sharp decrease in the frequency of splenic NK T cells in infected TNFR1 knockout (KO) mice. Anti-TNF-α therapy in TNFR1 KO mice significantly reduced chemokine production and liver injury. Combined, these data indicate a dysregulated antibacterial host response following intravenous Klebsiella infection in the absence of TNFR1 signaling, resulting in heightened cytokine production and hyperactivation of specific splenic lymphocyte subsets

Alegacion juridica por don Juan Gomez de Parada Fonseca Enriquez ... con don Joachin de Toledo Pimentel, Marquès de Malpica ... Bernardino Fernandez de Velasco, Duque de Frias ... Maria Josepha Pimentel Tellez Girón, Condesa Duquesa de Benavente ... y Fabricio Pignateli de Aragon Pimentel Enriquez, Duque de Terra-Nova, y Monte-Leon ... : sobre el articulo de administracion del Mayorazgo fundado de Medina de Rio-Seco, en la donacion de él, hecha por el Señor Rey Don Juan el II. a don Alfonso Enriquez ... vacantes por muerte de don Francisco Vigil de Quiñones, Conde de Benavente ... ultimo possehedor, o por la que sea mas legal

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Manifestacion sencilla de la verdad, y derecho que asiste a doña Gertrudis Gallo Villavicencio ... como madre ... de D. Juan Maria Gomez de Parada Fonseca Enriquez ... En el juicio con ... Maria Josepha Alphonso Pimentel, Condesa Duquesa de Benavente ... Pedro Alcantara Fernandez de Hijar, Duque de Hijar ... Bernardino Fernandez de Velasco Pimenlel Vigil de Quiñones, Duque de Frias ... Joachin de Toledo y Rivera, Marques de Malpica ... Fabricio Piñateli, Duque de Monteleon ... Hermenegildo Manuel Hurtado de Mendoza, Marques de Gelo y Villamayna ... y Joseph Ramon Enriquez ... : sobre la tenuta, y posesion del mayorazgo, fundado por D. Enrique Enriquez ... primer Conde de Alva de Aliste ... vacante ... por muerte de D. Francisco Antonio Pimentel, Conde Duque de Benavente ... su último Tenedor

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