Browsing by Author "Rapp, Christine M."

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    Acute Ethanol Exposure Augments Low-Dose UVB-Mediated Systemic Immunosuppression via Enhanced Production of Platelet-Activating Factor Receptor Agonists
    (Elsevier, 2019-01-22) Travers, Jeffrey B.; Weyerbacher, Jonathan; Ocana, Jesus A.; Borchers, Christina; Rapp, Christine M.; Sahu, Ravi P.; Dermatology, School of Medicine
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    Enhanced Platelet-activating Factor synthesis facilitates acute and delayed effects of ethanol intoxicated thermal burn injury
    (Elsevier, 2018) Harrison, Kathleen A.; Romer, Eric; Weyerbacher, Jonathan; Ocana, Jesus A.; Sahu, Ravi P.; Murphy, Robert C.; Kelly, Lisa E.; Smith, Townsend A.; Rapp, Christine M.; Borchers, Christina; Cool, David R.; Li, Gengxin; Simman, Richard; Travers, Jeffrey B.; Pharmacology and Toxicology, School of Medicine
    Thermal burn injuries in patients alcohol intoxicated result in greater morbidity and mortality. Murine models combining ethanol and localized thermal burn injury reproduce the systemic toxicity seen in human subjects, which consists of both acute systemic cytokine production with multiple organ dysfunction, as well as a delayed systemic immunosuppression. However, the exact mechanisms for these acute and delayed effects are unclear. These studies sought to define the role of the lipid mediator Platelet-activating factor (PAF) in the acute and delayed effects of intoxicated burn injury. Combining ethanol and thermal burn injury resulted in increased enzymatic PAF generation in a keratinocyte cell line in vitro, human skin explants ex vivo, as well as in murine skin in vivo. Further, the acute increase in inflammatory cytokines such as IL-6, and the systemic immunosuppressive effects of intoxicated thermal burn injury, were suppressed in mice lacking PAF receptors. Together, these studies provide a potential mechanism and novel treatment strategies for the augmented toxicity and immunosuppressive effects of thermal burn injury in the setting of acute ethanol exposure, which involves the pleotropic lipid mediator PAF.
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    Insights into Lichen Planus Pigmentosus Inversus using Minimally Invasive Dermal Patch and Whole Transcriptome Analysis
    (Avens Publishing Group, 2022) Dickman, Jacob; Howell, Michael; Hoopes, Robert; Wang, Yipeng; Dickerson, Tobin J.; Bottomley, Michael; Shamma, H. Nicholas; Rapp, Christine M.; Turner, Matthew J.; Rohan, Craig A.; Travers, Jeffrey B.; Dermatology, School of Medicine
    Lichen Planus Pigmentosus inversus (LPPi) is a rare interface and lichenoid dermatitis (ILD) and supposed variant of lichen planus (LP) that presents as well-demarcated brown to grey macules in flexural and intertriginous areas. LPPi is deemed 'inversus' because its anatomical distribution in skin folds is opposite that seen in lichen planus pigmentosus (LPP) whose pigmented lesions arise on sun-exposed skin. Biopsy is required for the clinical diagnosis of all ILDs. Though multiple clinically-oriented studies have reported differences between LPP, LPPi, and LP, few molecular studies have been performed. In this case study, 3 patients, 2 with LPPi and one with LP, provided samples using minimally invasive whole transcriptome analysis using a dermal biomarker patch. This study confirms the involvement of interferon signaling and T-cell activation in LPPi and suggests an expression profile distinct from LP. Specific genes significantly upregulated in LPPi vs LP include an intergenic splice variant of the primary pigmentation determining receptor in humans and dysregulation of genes essential for ceramide synthesis and construction of the cornified envelope. This work expands upon our knowledge of the pathogenesis of LPPi vs LP, and supports the potential use of this technology in the diagnostic clinical setting to mitigate the need for invasive procedures.