A5077112559- Ophthalmology and Eye Disorders
- Thyroid Disorders and Treatments
- Glaucoma and retinal disorders
- Receptor Mechanisms and Signaling
- Growth Hormone and Insulin-like Growth Factors
- Pituitary Gland Disorders and Treatments
- Inflammatory mediators and NSAID effects
- Multiple Sclerosis Research Studies
- Cancer, Stress, Anesthesia, and Immune Response
- Fibroblast Growth Factor Research
- Peripheral Neuropathies and Disorders
- Proteoglycans and glycosaminoglycans research
- Estrogen and related hormone effects
- Systemic Lupus Erythematosus Research
- Cerebral Venous Sinus Thrombosis
- Thyroid Cancer Diagnosis and Treatment
- Erythrocyte Function and Pathophysiology
- Diabetes and associated disorders
- Eicosanoids and Hypertension Pharmacology
- S100 Proteins and Annexins
- Immunodeficiency and Autoimmune Disorders
- Inflammatory Bowel Disease
- Ocular Surface and Contact Lens
- NF-κB Signaling Pathways
- Cell Adhesion Molecules Research
University of Michigan
2016-2025
Alberta Health Services
2024-2025
W.K. Kellogg Foundation
2009-2024
Michigan Medicine
2021-2024
Charité - Universitätsmedizin Berlin
2016-2024
Humboldt-Universität zu Berlin
2021-2024
Freie Universität Berlin
2021-2024
Max Delbrück Center
2021-2024
Michigan United
2010-2024
Einstein Center Digital Future
2024
Thyroid-associated ophthalmopathy, a condition commonly associated with Graves' disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition the insulin-like growth factor I receptor (IGF-IR) is new therapeutic strategy to attenuate underlying autoimmune pathogenesis ophthalmopathy.
Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food Drug Administration-approved medical therapy available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in pathogenesis of this disease.In randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned patients with active thyroid 1:1 ratio to receive intravenous infusions IGF-IR inhibitor teprotumumab (10 mg per kilogram...
Abstract Thyroid-stimulating hormone receptor (TSHR) plays a central role in regulating thyroid function and is targeted by IgGs Graves’ disease (GD-IgG). Whether TSHR involved the pathogenesis of thyroid-associated ophthalmopathy (TAO), orbital manifestation GD, remains uncertain. signaling overlaps with that insulin-like grow factor 1 (IGF-1R). GD-IgG can activate fibroblasts derived from donors GD to synthesize T cell chemoattractants hyaluronan, actions mediated through IGF-1R. In this...
The 2007 Recommendations of the International Commission on Radiological Protection (ICRP, 2007) introduced changes that affect calculation effective dose, and implied a revision dose coefficients for internal exposure, published previously in Publication 30 series 1979, 1980, 1981, 1988) 68 1994). In addition, new data are now available support an update radionuclide-specific information given Publications 54 78 1988a, 1997b) design monitoring programmes retrospective assessment...
Background: ‘No evidence of disease activity’ (NEDA), defined as absence magnetic resonance imaging activity (T2 and/or gadolinium-enhanced T1 lesions), relapses and disability progression (‘NEDA-3’), is used a comprehensive measure treatment response in relapsing multiple sclerosis (RMS), but weighted towards inflammatory activity. Accelerated brain volume loss (BVL) occurs RMS an objective worsening progression. Objective: To assess the contribution individual components NEDA-3 impact...
To evaluate teprotumumab safety/efficacy in patients with thyroid eye disease (TED) who were nonresponsive or experienced a flare.The Treatment of Graves' Orbitopathy to Reduce Proptosis Teprotumumab Infusions an Open-Label Clinical Extension Study (OPTIC-X) is treatment and re-treatment trial following the placebo-controlled Phase 3 (Thyroid Eye Disease) Randomized, Placebo-Controlled, (OPTIC) trial.Patients previously received placebo (n = 37) 14) OPTIC.OPTIC nonresponders those flared...
Abstract Graves’ disease (GD) is associated with T cell infiltration, but the mechanism for lymphocyte trafficking has remained uncertain. We reported previously that fibroblasts from patients GD express IL-16, a CD4-specific chemoattractant, and RANTES, C-C chemokine, in response to GD-specific IgG (GD-IgG). unexpectedly found these responses result functional interaction between GD-IgG insulin-like growth factor (IGF)-I receptor (IGF-IR). IGF-I IGF-IR-specific analog, des(1–3), mimic...
A distinctive histopathological feature associated with thyroid-associated ophthalmopathy is the disordered accumulation of glycosaminoglycan, hyaluronan, in orbital connective tissues. This often occurs context dramatic inflammation and tissue remodeling. Orbital fibroblasts exhibit a novel phenotype including exaggerated responses to cytokines. Here, we report for first time ability IgG isolated from sera patients Graves' disease (GD-IgG) provoke synthesis hyaluronan. The effect GD-IgG can...
Thyroid-associated ophthalmopathy, a process in which the orbital tissues become inflamed and are remodeled, occurs with variable presentation. In some patients, eye muscle enlargement predominates. others, connective/adipose tissue appears more significant problem. Orbital fibroblasts exhibit heterogeneous phenotypes culture. Here we report that derived from depot distinct those investing extraocular muscles. Connective represent bimodal population of cells regard to surface display...
The pathogenic basis for Graves' disease (GD) continues to elude our understanding. Specifically why activating antibodies are generated against self-antigens remains uncertain as does the identity of antigen(s) that provokes orbital involvement in GD, a process known thyroid-associated ophthalmopathy (TAO).The aim study was determine whether CD34(+) fibrocytes more frequently they infiltrate connective tissues TAO, and express thyrotropin receptor (TSHR).Generation from peripheral blood...
Human orbital fibroblasts play a putative role in the pathogenesis of thyroid-associated ophthalmopathy (TAO). We hypothesize that hyaluronan accumulation and inflammation TAO derive from enhanced biosynthetic activities fibroblasts. CD40, member tumor necrosis factor-α receptor superfamily, is critical signaling molecule expressed by B lymphocytes. Engagement CD40 with CD154 or ligand results activation target genes. Orbital also display CD40. Here we report engagement leads to substantial...