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Filter Results:

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Work 1-3 of 3

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Article

Mast cells are essential for early onset and severe disease in a murine model of multiple sclerosis

by Ginny Secor; W. Evan Secor; Claire-Anne Gutekunst; Melissa A. Brown

2000

Subjects
  • Health Sciences, Nursing
  • Health Sciences, Immunology
  • Biology, Molecular
  • File Download
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Abstract:Close

In addition to their well characterized role in allergic inflammation, recent data confirm that mast cells play a more extensive role in a variety of immune responses. However, their contribution to autoimmune and neurologic disease processes has not been investigated. Experimental allergic encephalomyelitis (EAE) and its human disease counterpart, multiple sclerosis, are considered to be CD4+ T cell-mediated autoimmune diseases affecting the central nervous system. Several lines of indirect evidence suggest that mast cells could also play a role in the pathogenesis of both the human and murine disease. Using a myelin oligodendrocyte glycoprotein (MOG)-induced model of acute EAE, we show that mast cell-deficient W/W(v) mice exhibit significantly reduced disease incidence, delayed disease onset, and decreased mean clinical scores when compared with their wild-type congenic littermates. No differences were observed in MOG-specific T and B cell responses between the two groups, indicating that a global T or B cell defect is not present in W/W(v) animals. Reconstitution of the mast cell population in W/W(v) mice restores induction of early and severe disease to wild-type levels, suggesting that mast cells are critical for the full manifestation of disease. These data provide a new mechanism for immune destruction in EAE and indicate that mast cells play a broader role in neurologic inflammation.

Article

Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson's disease

by Lori N. Eidson; George T. Kannarkat; Christopher J. Barnum; Jianjun Chang; Jaegwon Chung; Chelsea Caspell-Garcia; Peggy Taylor; Brit Mollenhauer; Michael G. Schlossmacher; Larry Ereshefsky; Mark Yen; Catherine Kopil; Mark Frasier; Kenneth Marek; Vicki Hertzberg; MariadeLourdes Tansey

2017

Subjects
  • Biology, Physiology
  • Health Sciences, Nursing
  • Health Sciences, General
  • File Download
  • View Abstract

Abstract:Close

Background: Efforts to identify fluid biomarkers of Parkinson's disease (PD) have intensified in the last decade. As the role of inflammation in PD pathophysiology becomes increasingly recognized, investigators aim to define inflammatory signatures to help elucidate underlying mechanisms of disease pathogenesis and aid in identification of patients with inflammatory endophenotypes that could benefit from immunomodulatory interventions. However, discordant results in the literature and a lack of information regarding the stability of inflammatory factors over a 24-h period have hampered progress. Methods: Here, we measured inflammatory proteins in serum and CSF of a small cohort of PD (n=12) and age-matched healthy control (HC) subjects (n=6) at 11 time points across 24h to (1) identify potential diurnal variation, (2) reveal differences in PD vs HC, and (3) to correlate with CSF levels of amyloid β (Aβ) and α-synuclein in an effort to generate data-driven hypotheses regarding candidate biomarkers of PD. Results: Despite significant variability in other factors, a repeated measures two-way analysis of variance by time and disease state for each analyte revealed that serum IFNγ, TNF, and neutrophil gelatinase-associated lipocalin (NGAL) were stable across 24h and different between HC and PD. Regression analysis revealed that C-reactive protein (CRP) was the only factor with a strong linear relationship between CSF and serum. PD and HC subjects showed significantly different relationships between CSF Aβ proteins and α-synuclein and specific inflammatory factors, and CSF IFNγ and serum IL-8 positively correlated with clinical measures of PD. Finally, linear discriminant analysis revealed that serum TNF and CSF α-synuclein discriminated between PD and HC with a minimum of 82% sensitivity and 83% specificity. Conclusions: Our findings identify a panel of inflammatory factors in serum and CSF that can be reliably measured, distinguish between PD and HC, and monitor inflammation as disease progresses or in response to interventional therapies. This panel may aid in generating hypotheses and feasible experimental designs towards identifying biomarkers of neurodegenerative disease by focusing on analytes that remain stable regardless of time of sample collection.

Article

Sleep Disturbance Among HIV-Infected and Uninfected Veterans

by Julie A. Womack; Terrence E. Murphy; Harini Bathulapalli; Kathleen M. Akgun; Cynthia Gibert; Ken M. Kunisaki; David Rimland; Maria Rodriguez-Barradas; H. Klar Yaggi; Amy C. Justice; Nancy S. Redeker

2017

Subjects
  • Health Sciences, Nursing
  • Health Sciences, General
  • File Download
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