A5044282307- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- Monoclonal and Polyclonal Antibodies Research
- Systemic Lupus Erythematosus Research
- Multiple Sclerosis Research Studies
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Immune Response and Inflammation
- Vestibular and auditory disorders
- Cancer Immunotherapy and Biomarkers
- Hearing, Cochlea, Tinnitus, Genetics
- Reproductive System and Pregnancy
- interferon and immune responses
- Cell Adhesion Molecules Research
- Neurogenesis and neuroplasticity mechanisms
- Cancer Research and Treatments
- Chemokine receptors and signaling
- Urinary Bladder and Prostate Research
- RNA Interference and Gene Delivery
- Glycosylation and Glycoproteins Research
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Research and Splicing
- RNA regulation and disease
Cleveland Clinic Lerner College of Medicine
2011-2023
Cleveland Clinic
2004-2023
Cleveland State University
2006-2022
Case Comprehensive Cancer Center
1994-2022
Case Western Reserve University
2009-2022
Breast Cancer Research Foundation
2014
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2008
Cerner (United States)
2002-2006
Shaker Heights Public Library
2004
Cleveland Foundation
1997
Mononuclear leukocytes preferentially accumulate in the central nervous system (CNS) during course of experimental autoimmune encephalomyelitis (EAE). To address factors that govern leukocyte trafficking EAE, we monitored expression nxRNAs encoding IP-10 and JE/MCP-1, which are members a family chemoattractant cytokines. A transient burst JE/MCP-1 mRNA accumulation CNS occurred, close relation to onset histologic clinical disease. In situ hybridizations showed, unexpectedly, astrocytes were...
Abstract PLP is the major protein constituent of central nervous system myelin. We have previously shown that SJL/J (H-2s) mice develop an acute form EAE after immunization with PLP. The purpose present study was to identify encephalitogenic determinant for SJL mice. immunized a synthetic peptide identical residues 130-147 QAHSLERVCHCLGKWLGH murine PLP, sequence having amphipathic alpha-helical conformation. Although it did not induce disease, overlapping containing 139-154 HCLGKWLGHPDKFVGI...
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Most patients undergo initial relapsing-remitting (RR-MS) course that transforms into a relentless neurodegenerative disorder, termed secondary progressive (SP)-MS. Reversible inflammation and demyelination account readily for pattern RR-MS but provide unsatisfactory explanation irrevocable decline in SP-MS. Axon loss thought to be responsible progressive, non-remitting neurological...
The development of autoimmune disease is accompanied by the acquired recognition new self-determinants, a process commonly referred to as determinant spreading. In this study, we addressed question whether spreading pathogenic for progression chronic-relapsing experimental encephalomyelitis (EAE), with many similarities multiple sclerosis (MS). Our approach involved systematic epitope mapping responses myelin proteolipid protein (PLP) well assaying known encephalitogenic determinants basic...
Recombinant interferon beta (IFNβ) benefits patients with relapsing remitting multiple sclerosis (MS), but the mechanisms of action are unknown. We studied in vivo immunologic effects IFNβ treatment and their relationship to clinical efficacy. Cytokines were measured blood CSF from MS participating a placebo-controlled phase III trial an open-label intravenous (IV) tolerability study IFNβ-1a. Additionally, studies conducted animals proteolipid protein (PLP)-induced chronic experimental...
We have previously used antibodies to the NG2 proteoglycan and alpha receptor for platelet-derived growth factor (PDGF α receptor) identify oligodendroglial progenitor cells in vivo vitro. It has recently become evident that GD3 antigen, which been widely as a marker oligodendrocyte cells, is also expressed by microglial cells. In this study we examined relationship between NG2+/PDGF receptor+ glial normal developing mature rat brain inflammatory lesions mice with experimental autoimmune...
Strains of mice with diverse genetic backgrounds were tested for susceptibility to experimental allergic encephalomyelitis (EAE) induced by myelin proteolipid protein. EAE was elicited in all strains tested, but the clinical and histologic features varied. SJL (H-2s) had a high incidence both disease characterized early onset signs. Inguinal lymph node T cells from diseased animals responded specifically [( 3H]thymidine incorporation) protein not basic In contrast, BALB/c (H-2d), DBA/1...
The migratory properties of memory T cells provide a model vector system for site-specific delivery therapeutic transgene factors to autoimmune inflammatory lesions. Lymph node from (SWRxSJL)F1 mice immunized with the p139-151 determinant myelin proteolipid protein (PLP) were transfected DNA construct that placed anti-inflammatory cytokine interleukin-10 (IL-10) cDNA under control an antigen-inducible IL-2 promoter region. Isolated cell clones demonstrated expression IL-10 and expressed...
Recent studies using murine animal model systems indicate that clinical progression of autoimmune disease may be due to the sequential accumulation neoautoreactivity characterized by extensive plasticity self recognition. In present study, we addressed question whether a similar paradigm recognition is implicated in development multiple sclerosis (MS), demyelinating with presumed etiology. Our approach was determine serial changes over 12-18-mo period response an epitope-mapping series 265...
Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for multiple sclerosis (MS). EAE typically initiated by CD4+ T helper cell type 1 (Th1) autoreactivity directed against single priming immunodominant myelin peptide determinant. Recent studies have shown that clinical progression of involves the accumulation neo-autoreactivity, commonly referred to as epitope spreading, determinants not involved in process. This study directly addresses relative roles primary and...
Tolerization of SJL/J mice with splenocytes coupled proteolipid protein (PLP), the major component central nervous system myelin, resulted in dramatic inhibition relapsing experimental autoimmune encephalomyelitis (R-EAE) induced by mouse spinal cord homogenate (MSCH). Mice tolerized MSCH (a complex mixture neuroantigens) or purified PLP, but not myelin basic protein, were resistant to development clinical and histologic R-EAE. In addition, rendered tolerant an encephalitogenic peptide PLP...
Immunization of animals with proteolipid protein, the major protein constituent central nervous system myelin, produces experimental allergic encephalomyelitis. The goal present study was to identify an encephalitogenic determinant this protein. For purpose, SWR mice were immunized five groups pooled synthetic peptides corresponding various regions myelin sequence. Clinical EAE observed in only one group. Inguinal lymph node cells from group responded ([3H]thymidine incorporation) a peptide...