A5039308003- Systemic Sclerosis and Related Diseases
- Animal testing and alternatives
- Systemic Lupus Erythematosus Research
- Eosinophilic Disorders and Syndromes
- Contact Dermatitis and Allergies
- Advancements in Transdermal Drug Delivery
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Autoimmune Bullous Skin Diseases
- Vaccine Coverage and Hesitancy
- Mast cells and histamine
- Immune Response and Inflammation
- Cell Adhesion Molecules Research
- Computational Drug Discovery Methods
- SARS-CoV-2 and COVID-19 Research
- T-cell and B-cell Immunology
- Urticaria and Related Conditions
- Veterinary Pharmacology and Anesthesia
- Pulmonary Hypertension Research and Treatments
- Dermatologic Treatments and Research
- Inflammatory Myopathies and Dermatomyositis
- Chemotherapy-induced cardiotoxicity and mitigation
- Hepatitis Viruses Studies and Epidemiology
- Pharmacological Effects of Natural Compounds
- Immunotoxicology and immune responses
- Dental Erosion and Treatment
Boston Medical Center
2007-2025
Boston University
2006-2021
University Medical Center
2007
Unilever (United Kingdom)
1992-2006
Breast Center
1997
Brigham and Women's Hospital
1997
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
1996
Harvard University
1996
PURPOSE To determine the cardioprotective effect of dexrazoxane (DZR) used in a doxorubicin-based combination therapy advanced breast cancer. PATIENTS AND METHODS Between November 1988 and January 1991, 534 patients with cancer were randomized to two multicenter, double-blind studies (088001 088006). Patients received fluorouracil, doxorubicin, cyclophosphamide (FAC) either DZR (DZR-to-doxorubicin ratio, 10:1) or placebo (PLA) every 3 weeks monitored serial multiplegated acquisition (MUGA)...
Plasmacytoid dendritic cells have been implicated in the pathogenesis of systemic sclerosis through mechanisms beyond previously suggested production type I interferon.We isolated plasmacytoid from healthy persons and patients with who had distinct clinical phenotypes. We then performed proteome-wide analysis validated these observations five large cohorts sclerosis. Next, we compared results those lupus erythematosus, ankylosing spondylitis, hepatic fibrosis. correlated plasma levels CXCL4...
Abstract Objective Microarray analyses of peripheral blood leukocytes have shown that patients with systemic lupus erythematosus express increased levels type I interferon (IFN)–regulated genes. In this study we examined gene expression by mononuclear cells (PBMCs) from sclerosis (SSc) to better understand the dysregulation immune system in disease. Methods PBMC was analyzed microarray and confirmed real‐time polymerase chain reaction (PCR). Surface protein Siglec‐1 flow cytometry PBMCs...
TGF-β has potent profibrotic activity in vitro and long been implicated systemic sclerosis (SSc), as expression of TGF-β-regulated genes is increased the skin lungs patients with SSc. Therefore, inhibition may benefit these patients.Patients early, diffuse cutaneous SSc were enrolled an open-label trial fresolimumab, a high-affinity neutralizing antibody that targets all 3 isoforms. Seven received two 1 mg/kg doses eight one 5 dose fresolimumab. Serial mid-forearm biopsies, performed before...
Abstract Objective To determine the safety of rituximab, to provide preliminary data regarding potential efficacy and investigate effects rituximab on autoimmunity fibrosis in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods Fifteen dcSSc, all whom experienced their first non–Raynaud's disease–associated disease manifestation within 18 months trial entry, were recruited receive 2 intravenous doses (1,000 mg), administered weeks apart. Safety, clinical, exploratory outcomes...
Recently adopted legislation in Europe has increased the focus that must be placed on development of vitro alternatives to traditional toxicology tests employed identify human health hazards associated with chemicals. Included these is rabbit skin‐irritation test which used discriminate those substances possess significant acute skin irritation potential from are more limited potential. So far, considerable efforts replace this assay have not been successful, may part due relatively poor...
Scleroderma (SSc) is a complex and heterogeneous connective tissue disease mainly characterized by autoimmunity, vascular damage, fibrosis that mostly involve the skin lungs. Epstein-Barr virus (EBV) lymphotropic γ-herpesvirus has co-evolved with human species, infecting >95% of adult population worldwide, been leading candidate in triggering several autoimmune diseases. Here we show EBV establishes infection majority fibroblasts endothelial cells SSc patients, expression noncoding small...
Monocytes/macrophages are activated in several autoimmune diseases, including systemic sclerosis (scleroderma; SSc), with increased expression of interferon (IFN)-regulatory genes and inflammatory cytokines, suggesting dysregulation the innate immune response autoimmunity. In this study, we investigated whether lytic form Epstein-Barr virus (EBV) infection (infectious EBV) is present scleroderma monocytes contributes to their activation SSc. Monocytes were isolated from peripheral blood...
Current regulations require that the skin irritation/corrosion potential of new chemicals is assessed in rabbit Draize test, although there are opportunities to use alternative methods identify most aggressive materials. Previously, we have proposed it possible la employ a strategy avoids animals and at same time delivers more relevant assessment irritation‐corrosion potential. The approach corrosive materials vitro then proceed human volunteer testing for irritation. In this study, 4‐h...
Despite the efficacy of COVID-19 vaccine in reducing mortality and illness severity, racial inequities vaccination uptake persist. Among individuals with rheumatologic conditions who are often immunocompromised, impact disparities preventive care threatens to widen existing adverse outcomes related infection. There exists an urgent need develop interventions that reduce hesitancy promote uptake. We leveraged long-standing community-academic partnerships two cities a curriculum will be part...
<h3>Background</h3> Systemic sclerosis (SSc) is an autoimmune disease and accumulating evidence suggests a role for Toll-like receptor (TLR)-mediated activation of dendritic cells (DCs). <h3>Objective</h3> To map TLR-mediated cytokine responses DCs from patients with SSc. <h3>Methods</h3> 45 SSc were included. Patients stratified as having diffuse cutaneous (dSSc) or limited (lSSc) according to the extent skin involvement, further divided into those late (>3 years) early (<2 years)....
The leukocyte, or beta2, integrins are heterodimeric cell surface molecules that share a common beta subunit, and have unique alpha subunits. LFA-1 is the predominant beta2 integrin on lymphocytes, plays an important role in many lymphocyte functions; however, most studies of cytoplasmic regions been performed transfected epithelial cells, such as COS, part because no lymphoid lines deficient subunit described. To address structure-function relevant types, two T lymphoblastoid clones...
The biological activity of skin‐sensitizing chemicals is related to their ability react, either directly or after metabolic activation, with appropriate skin proteins. For direct acting electrophilic compounds, this can be modelled, using the RAI (relative alkylation index) approach, by a combination electrophilicity and hydrophobicity parameters. Several structure‐activity relationships based on approach have been reported, but most them cover guinea pig sensitization test data what...
In patients with systemic sclerosis (SSc), the relationship between innate immune activation, represented by increased expression of interferon (IFN)-regulated genes, and vascular injury/activation, manifest endothelin-1 (ET-1), endothelin converting enzyme-1 (ECE1) intercellular adhesion molecule-1, is uncertain.To investigate potential roles ligands in both these pathogenic pathways.The effect known Toll-like receptor (TLR) was tested vitro on dermal microvascular pulmonary arterial...
Microvascular injury is considered an initial event in the pathogenesis of scleroderma and endothelial cells are suspected being target autoimmune process seen disease. EBV has long been proposed as a trigger for diseases, including scleroderma. Nevertheless, its contribution to pathogenic remains poorly understood. In this study, we report that lytic antigens detected dermal vessels, suggesting might represent infection skin. We show DNA load remarkably increased peripheral blood, plasma...