Effects of Antiepileptic Drugs on Immune Function in Human Subjects and Mice

A number of immune abnormalities have been found in epileptic patients treated with antiepileptic drugs (AED). The alterations seen range from mild suppression of immunoglobulins to severly impaired humoral and cellular immunities. There is evidence for both drug effects and genetic or acquired factors as contributors to these abnormalities. In order to examine the basis for immune abnormalities in patients with epilepsy, a number of experimental designs were employed: clinical studies, in vitro studies, and use of an animal model. Peripheral blood mononuclear cells (PBMC) isolated from epileptic patients currently receiving AED were found to have a reduced OKT4+/0KT8+ ratio. A reduced natural killer (NK) cell activity was found which may be due to a low proportion of Leu 11+ cells. A reduced NK cell activity was also found in healthy siblings of the patients, indicating a possible genetic basis for the level of this activity. Antibody-dependent cell-mediated cytotoxicity {ADCC), mitogenic responses, and total rosette-forming cells of PBMC isolated from patieots were found to be normal. The AED phenytoin has been associated with a variety of immune function alterations and lymphoma. In this study, phenytoin was found to depress basal and augmented NK cell activity of human cells in a dose-dependent manner in vitro. This depression was reversible following short-term exposure and at levels considered therapeutic. Phenytoin also depressed ADCC, thus one mechanism by which phenytoin alters immune function is by its depression of cell -mediated cytotoxicity. In contrast to results obtained with phenytoin, the AED carbamazepine did not significantly alter NK cell activity, but the diluent propylene glycol depressed activity. NFS mice given phenytoin produced lower specific antibody titers following antigen challenge. Body weights, specific organ weights for thymus, spleen, and liver, and blood cell counts were normal in these mice. The protocol was well tolerated by the animals at phenytoin dosages ranging from therapeutic to neurotoxic. Susceptibility to murine hepatitis virus was found to be increased in mice given a high dose of phenytoin. This animal model should allow investigations into toxic dose levels and mechanisms by which phenytoin and other AED alter immune function

Behavioural models for identifying authenticity in the Twitter feeds of UK Members of Parliament: a content analysis of UK MPs’ tweets between 2011 and 2012; a longitudinal study

That the public distrusts politicians is prevalent in both polling and academic literature (Uberoi & Apostolova, 2017; van der Meer, 2017; YouGov, 2017a, 2017b). Whether it's true that politicians cannot actually be trusted is really immaterial. If McCombs (2004) and Lippman (1922) are correct, and the media has an enormous impact on public opinion simply by establishing this dire narrative, then the perception of mistrust has become fact. Citizens are disengaged, misinformed, and weary. Politicians issue statements to meet political expediencies. Trust is a critical component of democracy, and only by behaving in a substantively new manner can politicians restore it. The irony is that this image cannot be artificially constructed; they must behave naturally and re-introduce themselves to a public sceptical of media training and spin. To restore trust they must present themselves as they truly are. They must behave authentically. This thesis examines the tweets made by UK MPs during 2011 and 2012 (n=774,467) for evidence of authenticity and establishes behavioural models that identify authentic talk in large Twitter datasets. The analytical .framework that defines authenticity and informs the content analysis is broadly based on the prior work examining authentic behaviour in reality TV conducted by Coleman (2006) that reveals performative characteristics that audiences are drawn to; Hall's (2009) examination of the good and bad effects of mediated communication on reality TV audiences; Liebes's (2001) examination of sincerity and humility in the performance of authenticity by politicians; Montgomery's (2001b) work examining the presence of authenticity in the press behaviour of UK MPs and his examination of Goffman's relevance to mediated communication (Montgomery, 2001a). This study also challenges Goffman's Dramaturgical theory which positions public communication either on stage or backstage by suggesting that the backstage is now performed onstage (Goffman, 1959, 1981). Additionally, this content analysis is informed by Henneberg and Scammell's examination of how competing perceptions of democratic theory can be used to evaluate a politician's political marketing techniques (Henneberg, Scammell, & O'Shaughnessy, 2009) and positions the behavioural models within these techniques. It is also important to note that the 774,467 tweets subjected to a quantitative and qualitative content analysis, as far as can be established, is the only large-scale longitudinal study of parliamentary Twitter behaviour. This study's contribution to knowledge is: 1. to examine of all the tweets produced by UK MPs between 2011-2012 (n=774,467) for evidence of authentic talk; 2. to memorialize their Twitter usage; 3. to establish behavioural models for identifying the presence of authenticity in the Twitter behaviour of politicians; 4. to organize these MPs into these new behavioural models; 5. to develop a mixed method research design for locating this behaviour in large sets of Twitter metadata. Works Cited Coleman, S. (2006). How the other half votes: Big Brother viewers and the 2005 general election. International Journal of Cultural Studies, 9(4), 457-479. doi: 10.1177 /1367877906069895 Goffman, E. (1959). The Presentation of Self in Everyday Life. Garden City, NY: Doubleday. Goffman, E. {1981). Forms of talk: University of Pennsylvania Press. Hall, A. (2009). Perceptions of the Authenticity of Reality Programs and Their Relationships to Audience Involvement, Enjoyment, and Perceived Learning. Journal of Broadcasting & Electronic Media, 53(4), 515 - 531. Henneberg, S. C., Scammell, M., & O'Shaughnessy, N. J. {2009). Political marketing management and theories of democracy. Marketing Theory, 9(2), 165-188. doi:10.1177 /1470593109103060 Liebes, T. (2001). "Look me straight in the eye," the political discourse of authenticity, spontaneity, and sincerity. The Communication Review, 4(4), 499 - 510. Lippman, W. (1922). Public Opinion. New York: Free Press. Mccombs, M. E. (2004). Setting the agenda: the mass media and public opinion. Montgomery, M. (2001a). Defining 'authentic talk'. Discourse Studies, 3(4), 397-405. Montgomery, M. {2001b). The uses of authenticity: "Speaking from experience" in a U.K. election broadcast. The Communication Review, 4(4), 447 - 462. Uberoi, E., & Apostolova, V. {2017). House of Commons Key Issues 2017: Political dis)engagement. London: House of Commons Retrieved from https://commonslibrary.parliament.uk/key-issues/political-disengagement/. van der Meer, T. W. G. (2017). Political Trust and the "Crisis of Democracy". In Oxford Research Encyclopedia - Politics: Oxford University Press. YouGov. (2017a). The problem of trust. Retrieved from https://yougov.co.uk/news/2012/11/13/problem-trust/ YouGov. (2017b). YouGov Trust Tracker. Retrieved from yougov.co.uk: https://yougov.co.uk/news/2012/11/13/problem-trust

Intratumoral IL-12 and TNF-α–Loaded Microspheres Lead To Regression of Breast Cancer and Systemic Antitumor Immunity

Background: Local, sustained delivery of cytokines at a tumor can enhance induction of antitumor immunity and may be a feasible neoadjuvant immunotherapy for breast cancer. We evaluated the ability of intratumoral poly-lactic-acid-encapsulated microspheres (PLAM) containing interleukin 12 (IL-12), tumor necrosis factor α (TNF-α), and granulocyte-macrophage colony stimulating factor (GM-CSF) in a murine model of breast cancer to generate a specific antitumor response.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41401/1/10434_2004_Article_147.pd

The crisis in public communication and the pursuit of authenticity: an analysis of the Twitter feeds of Scottish MPs 2008–2010

Twitter has made deep inroads into political communications over the past three years. It allows for endless real-time worldwide discussions, and is increasingly being used by politicians to engage citizens. However, this article considers how and whether Twitter opens up possibilities for gauging ‘authentic’ dialogue between politicians and citizens. ‘Authentic talk’ has been identified as ‘spontaneous, unrehearsed discourse’, and we suggest, in the context of crisis in public communication and its lament about the current state of political communication, that it may be an important component in the reconstruction of political trust between politicians and people. This article examines Twitter's use in presenting to citizens an ‘authentic’ view of Scottish Members of Parliament (MPs) and its conveyance of trust. In order to identify authentic talk, a content analysis has been undertaken on the entirety of Scottish MPs' tweets (n= 14,066) between 25 December 2008 (the earliest recorded tweet made by a Scottish MP) to 7 August 2010. Using bespoke content analysis software we mine this data set to identify occurrences of both authentic discourse and civic engagement. The findings conclude that authenticity is being conveyed and is quantifiable, opening a new avenue for the study of crisis theory