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One or more keywords matched the following properties of Glant, Tibor
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overview Originally as a physician, after spending three years in full-time research (Joint Diseases Laboratories, Shriners Hospital, Montreal, Canada and NIH/NIDR Bethesda), I have fundamentally changed my career converting my clinical experience and training to biomedical science. My major research interest during the past 30 years has been autoimmunity and autoimmune regulation of T and B cells in rheumatoid arthritis (RA) and ankylosing spondylitis (AS), and its corresponding animal models. I have generated monoclonal antibodies (mAbs) to cartilage antigenic components, and used these mAbs for immuno-electron microscopic localization of cartilage matrix molecules in aging and diseased cartilages. During the production of mAbs, serendipitously, I (and my immediate colleagues) “discovered” cartilage proteoglycan (PG) aggrecan-induced arthritis (PGIA) in genetically susceptible (arthritis-prone) BALB/c mice. I have had a long-standing interest and commitment to training of medical students for histopathology, and later on scientists and physician-scientists. In addition to mentoring pre- and postdoctoral trainees in my laboratory and faculty members, I was PI of numerous R01, P01 and R21 NIH grants; I was always funded since I moved to the USA. My early research was thymosin-producing epithelioid cells expected to control early T cell selection in mouse embryos and the mechanisms of Wasting syndrome. Simultaneously, I studied cartilage and bone development as well as cartilage repair and bone healing in animal models, and immunogenicity/antigenicity of cartilage and bone non-collagenous macromolecules. This included numerous histochemistry (mostly enzyme and immune histochemistry), biochemical and immunological methods. I was the first to localize proteoglycan (PG) aggrecan and link protein by immune electron microscopy in cartilage tissue, and first described the autoimmune potential of cartilage PG in patients with RA or ankylosing spondylitis. I/we have sequenced the core proteins of mouse and canine cartilage PG aggrecans, and described splice variants of human PG aggrecan. These pioneer studies were repeated and extended in many laboratories. My expertise in bone and cartilage biochemistry and biology was beneficial when I/we have studied the mechanism of aseptic loosening of total joint replacements, which studies then changed the orthopedic term/diagnosis from “cement disease” to “particulate disease”. Submicron-sized wear debris/particulates are phagocytized by macrophages, fibroblasts and osteoblast, trigger these cells to secrete pro-inflammatory cytokines and proteolytic enzymes leading to aseptic bone resorption and loosening of prosthetic device. After I/we described the PG (aggrecan)-induced arthritis (PGIA) in BALB/c mice in 1987, a large number of studies focused on the immune pathomechanism of this model of RA and mapping studies of (auto)epitopes. PGIA model shares similarities with RA as indicated by clinical assessments, laboratory tests, and histopathology of diarthrodial joints. The development of the disease in genetically susceptible mice is based upon the development of cross-reactive immune responses between the immunizing (human) and self (mouse) cartilage PG. The recessive inheritance of disease susceptibility, as in RA, is dictated by both MHC- and non-MHC-associated genes. I/we identified dominant (arthritic) and subdominant epitopes of human and mouse (self) PG, tested the arthritogenic potential of human cartilage PG, and I generated recombinant human G1 domain (a globular domain of PG which carry all arthritogenic epitopes. This model was used to test the efficacy of Leflunomide (component 418). Numerous laboratories use the PGIA model all over the world, and human studies led to the identification of citrullinated PG epitopes in RA patients. A fourth and most recent research direction is the genetic and epigenetic alterations in PGIA model and in RA patients. I/we identified over 25 quantitative trait loci (QTLs) in different genetic combination of F2 mice. A special select direction of these genetic studies was to generate congenic mice (a short resistant DBA2 allele in susceptible BALB/c background). These congenic mice were/are tested for arthritis susceptibility; genomic regions sequenced and mutated genes selected for in vitro and in vivo studies. Eight of these 25 QTL are syntenic with RA genomic risk loci. From these 8 overlapping RA risk loci we have selected mouse chromosomes 2 and 3, which are highly susceptible to arthritis and syntenic with human chromosomes 9 and 1. Mouse/human susceptible regions carry the PTPN22 (mChr3/hChr1) and C5/TRAF1/PHF19 (mChr2/hChr9) RA risk alleles. The mutated genes are studied in vitro and generating and testing gene-deficient mice for arthritis in susceptible BALB/c background, and allele-specific transgenic mice to rescue the gene deficiency-induced defect(s). My Scopus API key: 458a8af4ddad17c0c313a5e8b8454348 My Orcid ID: https://orcid.org/0000-0002-1706-3820 MY NIH COMMONS: TGLANT Research Areas: Autoimmunity, Rheumatoid Arthritis, Ankylosing Spondylitis, Genetics, Periprosthetic osteolysis My Faculty Profile at Rush University Medical Center: https://www.rushu.rush.edu/faculty/tibor-t-glant-md-phd Education: MD, University of Medical School (DOTE) Debrecen, Hungary PhD, University of Medical School (DOTE) Debrecen, Hungary DMsc. Hungarian Academy of Sciences, Budapest, Hungary
One or more keywords matched the following items that are connected to Glant, Tibor
Item TypeName
Concept Cytokines
Academic Article Lymphocyte responses in patients with total hip arthroplasty.
Academic Article Concentration- and composition-dependent effects of metal ions on human MG-63 osteoblasts.
Academic Article Cytokine-controlled RANKL and osteoprotegerin expression by human and mouse synovial fibroblasts: fibroblast-mediated pathologic bone resorption.
Academic Article The role of fibroblasts and fibroblast-derived factors in periprosthetic osteolysis.
Academic Article Human monocyte response to particulate biomaterials generated in vivo and in vitro.
Academic Article The role of adhesion molecules in the development of autoimmune arthritis.
Academic Article Mediators and autopathogenic effector cells in proteoglycan-induced arthritic and clinically asymptomatic BALB/c mice.
Academic Article Cellular mediators secreted by interfacial membranes obtained at revision total hip arthroplasty.
Academic Article New horizons in orthopaedic research: elucidation of cellular signal transduction pathways.
Academic Article Proteoglycan (aggrecan)-induced arthritis in BALB/c mice is a Th1-type disease regulated by Th2 cytokines.
Academic Article Complex pattern of Th1 and Th2 activation with a preferential increase of autoreactive Th1 cells in BALB/c mice with proteoglycan (aggrecan)-induced arthritis.
Academic Article Particulate wear debris activates protein tyrosine kinases and nuclear factor kappaB, which down-regulates type I collagen synthesis in human osteoblasts.
Academic Article Down-regulation of procollagen alpha1[I]] messenger RNA by titanium particles correlates with nuclear factor kappaB (NF-kappaB) activation and increased rel A and NF-kappaB1 binding to the collagen promoter.
Academic Article The potential role of the osteoblast in the development of periprosthetic osteolysis: review of in vitro osteoblast responses to wear debris, corrosion products, and cytokines and growth factors.
Academic Article Osteolysis: basic science.
Academic Article Th1 and Th2 cytokines regulate proteoglycan-specific autoantibody isotypes and arthritis.
Academic Article Continuous nasal administration of antigen is critical to maintain tolerance in adoptively transferred autoimmune arthritis in SCID mice.
Academic Article Sex effect on clinical and immunologic quantitative trait loci in a murine model of rheumatoid arthritis.
Academic Article Differential recognition of altered peptide ligands distinguishes two functionally discordant (arthritogenic and nonarthritogenic) autoreactive T cell hybridoma clones.
Academic Article Disease-associated qualitative and quantitative trait loci in proteoglycan-induced arthritis and collagen-induced arthritis.
Academic Article Proteoglycan aggrecan-induced arthritis: a murine autoimmune model of rheumatoid arthritis.
Academic Article T-cell recognition of differentially tolerated epitopes of cartilage proteoglycan aggrecan in arthritis.
Academic Article Molecular manipulation with the arthritogenic epitopes of the G1 domain of human cartilage proteoglycan aggrecan.
Academic Article Expression of CD44 and L-selectin in the innate immune system is required for severe joint inflammation in the proteoglycan-induced murine model of rheumatoid arthritis.
Academic Article The role of B cells in animal models of rheumatoid arthritis.
Academic Article Cartilage proteoglycan aggrecan epitopes induce proinflammatory autoreactive T-cell responses in rheumatoid arthritis and osteoarthritis.
Academic Article BALB/c mice genetically susceptible to proteoglycan-induced arthritis and spondylitis show colony-dependent differences in disease penetrance.
Academic Article Osteoarthritis-like damage of cartilage in the temporomandibular joints in mice with autoimmune inflammatory arthritis.
Academic Article Alteration in the gene encoding protein tyrosine phosphatase nonreceptor type 6 (PTPN6/SHP1) may contribute to neutrophilic dermatoses.
Academic Article Neutralization of IL-17 ameliorates uveitis but damages photoreceptors in a murine model of spondyloarthritis.
Academic Article Disease-promoting and -protective genomic loci on mouse chromosomes 3 and 19 control the incidence and severity of autoimmune arthritis.
Academic Article Pharmacogenetics and pharmacogenomics in rheumatology.
Academic Article Location of CD4+ T cell priming regulates the differentiation of Th1 and Th17 cells and their contribution to arthritis.
Academic Article Of mice and men: how animal models advance our understanding of T-cell function in RA.
Academic Article Rheumatoid arthritis vaccine therapies: perspectives and lessons from therapeutic ligand epitope antigen presentation system vaccines for models of rheumatoid arthritis.
Academic Article Immune Recognition of Citrullinated Proteoglycan Aggrecan Epitopes in Mice with Proteoglycan-Induced Arthritis and in Patients with Rheumatoid Arthritis.
Academic Article ZAP-70 Regulates Autoimmune Arthritis via Alterations in T Cell Activation and Apoptosis.
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  • Cytokines