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Search Results: 1 - 10 of 220714 matches for " Peter D. Walzer "
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Pneumocystis murina colonization in immunocompetent surfactant protein A deficient mice following environmental exposure
Michael J Linke, Alan D Ashbaugh, Jeffery A Demland, Peter D Walzer
Respiratory Research , 2009, DOI: 10.1186/1465-9921-10-10
Abstract: To analyze the role of SP-A in protecting the immunocompetent host from Pneumocystis colonization, the susceptibility of immunocompetent mice deficient in SP-A (KO) and wild-type (WT) mice to P. murina colonization was analyzed by reverse-transcriptase quantitative PCR (qPCR) and serum antibodies were measured by enzyme-linked immunosorbent assay (ELISA).Detection of P. murina specific serum antibodies in immunocompetent WT and KO mice indicated that the both strains of mice had been exposed to P. murina within the animal facility. However, P. murina mRNA was only detected by qPCR in the lungs of the KO mice. The incidence and level of the mRNA expression peaked at 8–10 weeks and declined to undetectable levels by 16–18 weeks. When the mice were immunosuppressed, P. murina cyst forms were also only detected in KO mice. P. murina mRNA was detected in SCID mice that had been exposed to KO mice, demonstrating that the immunocompetent KO mice are capable of transmitting the infection to immunodeficient mice. The pulmonary cellular response appeared to be responsible for the clearance of the colonization. More CD4+ and CD8+ T-cells were recovered from the lungs of immunocompetent KO mice than from WT mice, and the colonization in KO mice depleted CD4+ cells was not cleared.These data support an important role for SP-A in protecting the immunocompetent host from P. murina colonization, and provide a model to study Pneumocystis colonization acquired via environmental exposure in humans. The results also illustrate the difficulties in keeping mice from exposure to P. murina even when housed under barrier conditions.Pneumocystis spp. are ubiquitous fungal opportunistic pulmonary pathogens found, in man as well as in wild, domesticated, and laboratory animals. Pneumocystis spp. are host specific and cross infection between hosts has not been identified [1]. In humans, P. jirovecii is a significant cause of pneumonia in immunocompromised patients and despite effective treatmen
Humoral Immune Responses to Pneumocystis jirovecii Antigens in HIV-Infected and Uninfected Young Children with Pneumocystis Pneumonia
Kpandja Djawe, Kieran R. Daly, Linda Levin, Heather J. Zar, Peter D. Walzer
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0082783
Abstract: Background Humoral immune responses in human immunodeficiency virus (HIV)-infected and uninfected children with Pneumocystis pneumonia (PcP) are poorly understood. Methods Consecutive children hospitalized with acute pneumonia, tachypnea, and hypoxia in South Africa were investigated for PcP, which was diagnosed by real-time polymerase chain reaction on lower respiratory tract specimens. Serum antibody responses to recombinant fragments of the carboxyl terminus of Pneumocystis jirovecii major surface glycoprotein (MsgC) were analyzed. Results 149 children were enrolled of whom 96 (64%) were HIV-infected. PcP occurred in 69 (72%) of HIV-infected and 14 (26%) of HIV-uninfected children. HIV-infected children with PcP had significantly decreased IgG antibodies to MsgC compared to HIV-infected patients without PcP, but had similar IgM antibodies. In contrast, HIV-uninfected children with PcP showed no change in IgG antibodies to MsgC, but had significantly increased IgM antibodies compared to HIV-uninfected children without PCP. Age was an independent predictor of high IgG antibodies, whereas PcP was a predictor of low IgG antibodies and high IgM antibodies. IgG and IgM antibody levels to the most closely related MsgC fragments were predictors of survival from PcP. Conclusions Young HIV-infected children with PcP have significantly impaired humoral immune responses to MsgC, whereas HIV-uninfected children with PcP can develop active humoral immune responses. The children also exhibit a complex relationship between specific host factors and antibody levels to MsgC fragments that may be related to survival from PcP.
Intra- and Trans-Generational Costs of Reduced Female Body Size Caused by Food Limitation Early in Life in Mites
Andreas Walzer, Peter Schausberger
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0079089
Abstract: Background Food limitation early in life may be compensated for by developmental plasticity resulting in accelerated development enhancing survival at the expense of small adult body size. However and especially for females in non-matching maternal and offspring environments, being smaller than the standard may incur considerable intra- and trans-generational costs. Methodology/Principal Findings Here, we evaluated the costs of small female body size induced by food limitation early in life in the sexually size-dimorphic predatory mite Phytoseiulus persimilis. Females are larger than males. These predators are adapted to exploit ephemeral spider mite prey patches. The intra- and trans-generational effects of small maternal body size manifested in lower maternal survival probabilities, decreased attractiveness for males, and a reduced number and size of eggs compared to standard-sized females. The trans-generational effects of small maternal body size were sex-specific with small mothers producing small daughters but standard-sized sons. Conclusions/Significance Small female body size apparently intensified the well-known costs of sexual activity because mortality of small but not standard-sized females mainly occurred shortly after mating. The disadvantages of small females in mating and egg production may be generally explained by size-associated morphological and physiological constraints. Additionally, size-assortative mate preferences of standard-sized mates may have rendered small females disproportionally unattractive mating partners. We argue that the sex-specific trans-generational effects were due to sexual size dimorphism – females are the larger sex and thus more strongly affected by maternal stress than the smaller males – and to sexually selected lower plasticity of male body size.
Echinocandin Treatment of Pneumocystis Pneumonia in Rodent Models Depletes Cysts Leaving Trophic Burdens That Cannot Transmit the Infection
Melanie T. Cushion,Michael J. Linke,Alan Ashbaugh,Tom Sesterhenn,Margaret S. Collins,Keeley Lynch,Ronald Brubaker,Peter D. Walzer
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0008524
Abstract: Fungi in the genus Pneumocystis cause pneumonia (PCP) in hosts with debilitated immune systems and are emerging as co-morbidity factors associated with chronic diseases such as COPD. Limited therapeutic choices and poor understanding of the life cycle are a result of the inability of these fungi to grow outside the mammalian lung. Within the alveolar lumen, Pneumocystis spp., appear to have a bi-phasic life cycle consisting of an asexual phase characterized by binary fission of trophic forms and a sexual cycle resulting in formation of cysts, but the life cycle stage that transmits the infection is not known. The cysts, but not the trophic forms, express β -1,3-D-glucan synthetase and contain abundant β -1,3-D-glucan. Here we show that therapeutic and prophylactic treatment of PCP with echinocandins, compounds which inhibit the synthesis of β -1,3-D-glucan, depleted cysts in rodent models of PCP, while sparing the trophic forms which remained in significant numbers. Survival was enhanced in the echincandin treated mice, likely due to the decreased β -1,3-D-glucan content in the lungs of treated mice and rats which coincided with reductions of cyst numbers, and dramatic remodeling of organism morphology. Strong evidence for the cyst as the agent of transmission was provided by the failure of anidulafungin-treated mice to transmit the infection. We show for the first time that withdrawal of anidulafungin treatment with continued immunosuppression permitted the repopulation of cyst forms. Treatment of PCP with an echinocandin alone will not likely result in eradication of infection and cessation of echinocandin treatment while the patient remains immunosuppressed could result in relapse. Importantly, the echinocandins provide novel and powerful chemical tools to probe the still poorly understood bi-phasic life cycle of this genus of fungal pathogens.
Serum Antibody Levels to the Pneumocystis jirovecii Major Surface Glycoprotein in the Diagnosis of P. jirovecii Pneumonia in HIV+ Patients
Kpandja Djawe,Laurence Huang,Kieran R. Daly,Linda Levin,Judy Koch,Alexandra Schwartzman,Serena Fong,Brenna Roth,Anuradha Subramanian,Katherine Grieco,Leah Jarlsberg,Peter D. Walzer
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0014259
Abstract: Pneumocystis jirovecii remains an important cause of fatal pneumonia (Pneumocystis pneumonia or PcP) in HIV+ patients and other immunocompromised hosts. Despite many previous attempts, a clinically useful serologic test for P. jirovecii infection has never been developed.
Serologic Responses to Recombinant Pneumocystis jirovecii Major Surface Glycoprotein among Ugandan Patients with Respiratory Symptoms
Robert J. Blount, Leah G. Jarlsberg, Kieran R. Daly, William Worodria, J. Lucian Davis, Adithya Cattamanchi, Kpandja Djawe, Alfred Andama, Judith Koch, Peter D. Walzer, Laurence Huang, International HIV-Associated Opportunistic Pneumonias (IHOP) Study
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0051545
Abstract: Background Little is known about the serologic responses to Pneumocystis jirovecii major surface glycoprotein (Msg) antigen in African cohorts, or the IgM responses to Msg in HIV-positive and HIV-negative persons with respiratory symptoms. Methods We conducted a prospective study of 550 patients, both HIV-positive (n = 467) and HIV-negative (n = 83), hospitalized with cough ≥2 weeks in Kampala, Uganda, to evaluate the association between HIV status, CD4 cell count, and other clinical predictors and antibody responses to P. jirovecii. We utilized ELISA to measure the IgM and IgG serologic responses to three overlapping recombinant fragments that span the P. jirovecii major surface glycoprotein: MsgA (amino terminus), MsgB (middle portion) and MsgC1 (carboxyl terminus), and to three variations of MsgC1 (MsgC3, MsgC8 and MsgC9). Results HIV-positive patients demonstrated significantly lower IgM antibody responses to MsgC1, MsgC3, MsgC8 and MsgC9 compared to HIV-negative patients. We found the same pattern of low IgM antibody responses to MsgC1, MsgC3, MsgC8 and MsgC9 among HIV-positive patients with a CD4 cell count <200 cells/μl compared to those with a CD4 cell count ≥200 cells/μl. HIV-positive patients on PCP prophylaxis had significantly lower IgM responses to MsgC3 and MsgC9, and lower IgG responses to MsgA, MsgC1, MsgC3, and MsgC8. In contrast, cigarette smoking was associated with increased IgM antibody responses to MsgC1 and MsgC3 but was not associated with IgG responses. We evaluated IgM and IgG as predictors of mortality. Lower IgM responses to MsgC3 and MsgC8 were both associated with increased in-hospital mortality. Conclusions HIV infection and degree of immunosuppression are associated with reduced IgM responses to Msg. In addition, low IgM responses to MsgC3 and MsgC8 are associated with increased mortality.
Ambient Air Pollution Associated with Suppressed Serologic Responses to Pneumocystis jirovecii in a Prospective Cohort of HIV-Infected Patients with Pneumocystis Pneumonia
Robert J. Blount, Kpandja Djawe, Kieran R. Daly, Leah G. Jarlsberg, Serena Fong, John Balmes, Robert F. Miller, Peter D. Walzer, Laurence Huang, on behalf of the International HIV-associated Opportunistic Pneumonias (IHOP) Study.
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0080795
Abstract: Background Ambient air pollution (AAP) may be associated with increased risk for Pneumocystis pneumonia (PCP). The mechanisms underlying this association remain uncertain. Objectives To determine if real-life exposures to AAP are associated with suppressed IgM antibody responses to P. jirovecii in HIV-infected (HIV+) patients with active PCP, and to determine if AAP, mediated by suppressed serologic responses to Pneumocystis, is associated with adverse clinical outcomes. Methods We conducted a prospective cohort study in HIV+ patients residing in San Francisco and admitted to San Francisco General Hospital with microscopically confirmed PCP. Our AAP predictors were ambient air concentrations of particulate matter of < 10 μm in diameter (PM10) and < 2.5 μm in diameter (PM2.5), nitrogen dioxide (NO2), ozone (O3), and sulfur dioxide (SO2) measured immediately prior to hospital admission and 2 weeks prior to admission. Our primary outcomes were the IgM serologic responses to four recombinant P. jirovecii major surface glycoprotein (Msg) constructs: MsgC1, MsgC3, MsgC8, and MsgC9. Results Elevated PM10 and NO2 exposures immediately prior to and two weeks prior to hospital admission were associated with decreased IgM antibody responses to P. jirovecii Msg. For exposures immediately prior to admission, every 10 μg/m3 increase in PM10 was associated with a 25 to 35% decrease in IgM responses to Msg (statistically significant for all the Msg constructs), and every 10 ppb increase in NO2 was associated with a 19-45% decrease in IgM responses to Msg (statistically significant for MsgC8 and MsgC9). Similar findings were seen with exposures two weeks prior to admission, but for fewer of the Msg constructs. Conclusions Real life exposures to PM10 and NO2 were associated with suppressed IgM responses to P. jirovecii Msg in HIV+ patients admitted with PCP, suggesting a mechanism of immunotoxicity by which AAP increases host susceptibility to pulmonary infection.
Arte y Publicidad: Elementos para debate
Aisthesis , 2010, DOI: 10.4067/S0718-71812010000100021
Abstract: this article presents an advance for discussion about the relationship between advertising and art. some authors have argued that advertising is an art in times when art has died. however, we will discuss this statement considering the logic of these two different fields, both image and aesthetic production. to that effect, we will focus on the purposes, addressees and authorship, all of them in regard to the arts and advertising.
Arte y Publicidad: Elementos para debate Art and Advertising: Issues for Debate
Alejandra Walzer
Aisthesis , 2010,
Abstract: En este artículo se presentan algunos elementos para el debate en torno a la relación entre publicidad y arte. Algunos autores han se alado que la publicidad es el arte en la era de la muerte del arte, sin embargo, discutiremos esta afirmación tomando como punto de anclaje la diferente lógica de estos dos campos de la producción imaginística y estética. Para ello nos centraremos en los fines, en los destinatarios y en la autoría, tanto en lo referido a las artes como a la publicidad. This article presents an advance for discussion about the relationship between advertising and art. Some authors have argued that advertising is an art in times when art has died. However, we will discuss this statement considering the logic of these two different fields, both image and aesthetic production. To that effect, we will focus on the purposes, addressees and authorship, all of them in regard to the arts and advertising.
Just and Unjust Wars, Prólogo a la tercera edición.
Michael WALZER
Relaciones Internacionales , 2006,
Abstract: La obra de Michael Walzer es una de las claves para entender el resurgimiento de la Guerra Justa que pudo observarse en los a os 90. El prólogo, a través del ejemplo de la Guerra del Golfo, ilustra sobre como las decisiones políticas o militares que desembocan en un conflicto armado, constituyen un problema moral de primer orden que repercute en los propios combatientes, así como en la población civil y sobre el que es necesario debatir. Walzer plantea problemas de enorme actualidad como la cuestión del pacifismo y sus consecuencias, la necesidad de distinguir y justificar el derecho a la guerra o el derecho en la guerra y poner de manifiesto que solo la existencia de una regulación normativa sobre la Guerra Justa permitirá conseguir el objetivo de que deje de ser un recurso ilimitado. Michael Walzer′s book is one of the keys to understanding the resurgence of the Just War during the 1990′s. Through the use of the Gulf War as an example, the Prologue explains how the political or military decisions that lead to war constitute a moral dilemma with consequences not only for the combatants, but also for the civilian population, thus representing an issue that must be debated. Walzer takes on current issues such as the pacifist question and its consequences, the need to distinguish and to justify the Ius ad Bellum and Ius in Bello, and to explain that only a normative regulation for Just War will avoid the consideration for war as an unlimited resort.
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