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Bannach O.,Heinrich Heine University Düsseldorf | Birkmann E.,Heinrich Heine University Düsseldorf | Birkmann E.,Jülich Research Center | Reinartz E.,Heinrich Heine University Düsseldorf | And 10 more authors.
PLoS ONE | Year: 2012

Prion diseases are transmissible neurodegenerative diseases affecting humans and animals. The agent of the disease is the prion consisting mainly, if not solely, of a misfolded and aggregated isoform of the host-encoded prion protein (PrP). Transmission of prions can occur naturally but also accidentally, e.g. by blood transfusion, which has raised serious concerns about blood product safety and emphasized the need for a reliable diagnostic test. In this report we present a method based on surface-FIDA (fluorescence intensity distribution analysis), that exploits the high state of molecular aggregation of PrP as an unequivocal diagnostic marker of the disease, and show that it can detect infection in blood. To prepare PrP aggregates from blood plasma we introduced a detergent and lipase treatment to separate PrP from blood lipophilic components. Prion protein aggregates were subsequently precipitated by phosphotungstic acid, immobilized on a glass surface by covalently bound capture antibodies, and finally labeled with fluorescent antibody probes. Individual PrP aggregates were visualized by laser scanning microscopy where signal intensity was proportional to aggregate size. After signal processing to remove the background from low fluorescence particles, fluorescence intensities of all remaining PrP particles were summed. We detected PrP aggregates in plasma samples from six out of ten scrapie-positive sheep with no false positives from uninfected sheep. Applying simultaneous intensity and size discrimination, ten out of ten samples from scrapie sheep could be differentiated from uninfected sheep. The implications for ante mortem diagnosis of prion diseases are discussed. © 2012 Bannach et al.

Young M.R.I.,Medical Research Service 151 | Young M.R.I.,Medical University of South Carolina | Levingston C.,Medical Research Service 151 | Johnson S.D.,Medical University of South Carolina
Cancers | Year: 2015

Differences in levels of inflammation-modulating cytokines and adipokines in patients with premalignant oral lesions versus in patients that develop squamous cell carcinoma of the head and neck (HNSCC) were assessed. Also assessed was the impact of treating HNSCC patients with the immune regulatory mediator, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], on modulators of inflammation. Compared to healthy controls, patients with premalignant oral lesions had increases in their systemic levels of the inflammatory cytokines IL-6 and IL-17, and increases in the adipokine, leptin. However, levels of these pro-inflammatory cytokines and adipokine were reduced in patients with HNSCC. Treatment of HNSCC patients with 1,25(OH)2D3 increased levels of each of the measured immune mediators. Levels of the anti-inflammatory adipokine, adiponectin, were shifted inversely with the levels of the pro-inflammatory cytokines and with leptin. These studies demonstrate heightened immune reactivity in patients with premalignant lesions, which wanes in patients with HNSCC, but which is restored by treatment with 1,25(OH)2D3. © 2015 by the authors; licensee MDPI, Basel, Switzerland.

Johnson S.D.,Medical University of South Carolina | De Costa A.-M.A.,Medical University of South Carolina | Young M.R.I.,Medical University of South Carolina | Young M.R.I.,Medical Research Service 151
Cancers | Year: 2014

Head and neck squamous cell carcinoma (HNSCC) is marked by immunosuppression, a state in which the established tumor escapes immune attack. However, the impact of the premalignant and tumor microenvironments on immune reactivity has yet to be elucidated. The purpose of this study was to determine how soluble mediators from cells established from carcinogen-induced oral premalignant lesions and HNSCC modulate immune cell cytokine production. It was found that premalignant cells secrete significantly increased levels of G-CSF, RANTES, MCP-1, and PGE2 compared to HNSCC cells. Splenocytes incubated with premalignant supernatant secreted significantly increased levels of Th1-, Th2-, and Th17-associated cytokines compared to splenocytes incubated with HNSCC supernatant. These studies demonstrate that whereas the premalignant microenvironment elicits proinflammatory cytokine production, the tumor microenvironment is significantly less immune stimulatory and may contribute to immunosuppression in established HNSCC. © 2014 by the authors; licensee MDPI, Basel, Switzerland.

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