3 results
2262: The impact of alcohol dysbiosis on host defense against pneumonia
- Derrick Richard Samuelson, Vincent Maffei, Eugene Blanchard, Meng Luo, Christopher Taylor, Judd Shellito, Martin Ronis, Patricia Molina, David Welsh
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- Journal:
- Journal of Clinical and Translational Science / Volume 1 / Issue S1 / September 2017
- Published online by Cambridge University Press:
- 10 May 2018, pp. 4-5
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- Article
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OBJECTIVES/SPECIFIC AIMS: Alcohol consumption perturbs the normal intestinal microbial communities (alcohol dysbiosis). To begin to investigate the relationship between alcohol-mediated dysbiosis and host defense we developed an alcohol dysbiosis fecal adoptive transfer model, which allows us to isolate the host immune response to a pathogenic challenge at a distal organ (ie, the lung). This model system allowed us to determine whether the host immune responses to Klebsiella pneumoniae are altered by ethanol-associated dysbiosis, independent of alcohol use. We hypothesized that alcohol-induced changes in intestinal microbial communities would impair pulmonary host defenses against K. pneumoniae. METHODS/STUDY POPULATION: Mice were treated with a cocktail of antibiotics daily for 2 weeks. Microbiota-depleted mice were then recolonized by gavage for 3-days with intestinal microbiota from ethanol-fed or pair-fed animals. Following recolonization groups of mice were sacrificed prior to and 48 hours post respiratory infection with K. pneumoniae. We then assessed susceptibility to Klebsiella infection by determining colony counts for pathogen burden in the lungs. We also determined lung and intestinal immunology, intestinal permeability, as well as, liver damage and inflammation. RESULTS/ANTICIPATED RESULTS: We found that increased susceptibility to K. pneumoniae is, in part, mediated by the intestinal microbiota, as animals recolonized with an alcohol-induced dysbiotic intestinal microbial community have significantly higher lung burdens of K. pneumoniae (5×104 CFU vs. 1×103 CFU) independent of EtOH. We also found that increased susceptibility in alcohol-dysbiosis recolonized animals was associated with a decrease in the recruitment and/or proliferation of CD4+ and CD8+ T-cells (1.5×109 cells vs. 2.5×109 cells) in the lung following Klebsiella infection. However, there were increased numbers of T-cells in the intestinal tract following Klebsiella infection, which may suggest that T cells are being sequestered in the intestinal tract to the detriment of host defense in the lung. Interestingly, mice recolonized with an alcohol-dysbiotic microbiota had increased intestinal permeability as measured by increased levels of serum intestinal fatty acid binding protein (55 vs. 30 ng/mL). Alcohol-dysbiotic microbiota also increased liver steatosis (Oil Red-O staining) and liver inflammation (>2-fold expression of IL-17 and IL-23). DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings suggest that the commensal intestinal microbiota support mucosal host defenses against infectious agents by facilitating normal immune responses to pulmonary pathogens. Our data also suggest that increased intestinal permeability coupled with increased liver inflammation may impair the recruitment/proliferation of immune cells in the respiratory tract following infection. The role of the microbiota during host defense will be important areas of future research directed at understanding the effects of microbial dysbiosis in patients with AUDs.
The Constitutional Sanity of James Otis: Resistance Leader and Loyal Subject
- Richard A. Samuelson
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- Journal:
- The Review of Politics / Volume 61 / Issue 3 / Summer 1999
- Published online by Cambridge University Press:
- 05 August 2009, pp. 493-524
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This article argues that we can best understand the Massachusetts patriot James Otis as a practical political thinker whose writings reacted to changing circumstances and to other writers. He began his career arguing that the British Constitution and natural law both mandated that Parliament not tax unrepresented colonists, but when Blackstone published his opinion that Parliament had a natural and constitutional right to compel the submission of the colonists, Otis became convinced that, however valid his argument had been in theory, it would never convince Parliamentarians. Ultimately he engaged the problem of imperial structure, trying to collapse the political distance between the imperial periphery and the imperial center to overcome the constitutional distance that threatened to separate them for good.
10 - Jefferson and religion: private belief, public policy
- Edited by Frank Shuffelton, University of Rochester, New York
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- Book:
- The Cambridge Companion to Thomas Jefferson
- Published online:
- 28 May 2009
- Print publication:
- 22 January 2009, pp 143-154
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Summary
Jefferson was of two minds on the subject of religion, which has sometimes confused both his critics and his champions. He wrote John Adams in 1817: “If by religion we are to understand sectarian dogmas, in which no two of them agree, then your exclamation on that hypothesis is just, “that this would be the best of all possible worlds, if there were no religion in it.” But if the moral precepts, innate in man, and made a part of his physical constitution, as necessary for a social being, if the sublime doctrines of philanthropism and deism taught us by Jesus of Nazareth, in which all agree, constitute true religion, then, without it, this would be, as you again say, “something not fit to be named” even, indeed, a hell.” Jefferson had little use for the “sectarian dogmas” which were commonly called “religion,” yet he believed that “the moral precepts, innate in man,” were essential. The latter constituted “true religion.” There are two sides to the story of Jefferson's religious ideas - private and public. What were Jefferson's personal religious beliefs? And what did Jefferson mean when he said in his famous letter to the Danbury Baptists that there ought to be a “wall of separation between church and state.” / Jefferson's religious journey / Jefferson's religious opinions changed as he aged. Jefferson's family raised him in the Anglican church. Either before or during his college years, he drifted away from whatever Christian faith he had, and remained rather skeptical through much of his adulthood. In the mid-1790s, or perhaps a bit before then, he started to study the life, works, and philosophy of Jesus quite closely. In time he would edit his own, personal edition of the Gospels and would think that Jesus was one of history's greatest moral teachers.