A5006314383- Systemic Sclerosis and Related Diseases
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Immunotherapy and Immune Responses
- Inflammatory Myopathies and Dermatomyositis
- Cannabis and Cannabinoid Research
- Immune Cell Function and Interaction
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- Virus-based gene therapy research
- Medical Imaging and Pathology Studies
- Cancer Immunotherapy and Biomarkers
- Dermatologic Treatments and Research
- Neuroscience of respiration and sleep
- Immune cells in cancer
- Inflammatory mediators and NSAID effects
- Asthma and respiratory diseases
- RNA Interference and Gene Delivery
- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- Pancreatic function and diabetes
- Voice and Speech Disorders
- Diet, Metabolism, and Disease
- Mast cells and histamine
- Pericarditis and Cardiac Tamponade
University of California, Los Angeles
2016-2025
UCLA Health
2011-2024
Walter Reed National Military Medical Center
2024
Nippon Medical School
2023
The University of Texas Health Science Center at Houston
2023
Pulmonary and Critical Care Associates
1988-2018
McMaster University
2018
St. Joseph’s Healthcare Hamilton
2018
Scleroderma Foundation
2017
University of Michigan
2017
We conducted a double-blind, randomized, placebo-controlled trial to determine the effects of oral cyclophosphamide on lung function and health-related symptoms in patients with evidence active alveolitis scleroderma-related interstitial disease.At 13 clinical centers throughout United States, we enrolled 158 scleroderma, restrictive physiology, dyspnea, inflammatory disease examination bronchoalveolar-lavage fluid, thoracic high-resolution computed tomography, or both. Patients received (<...
Abstract Purpose: We previously reported that autologous dendritic cells pulsed with acid-eluted tumor peptides can stimulate T cell–mediated antitumor immune responses against brain tumors in animal models. As a next step vaccine development, phase I clinical trial was established to evaluate this strategy for its feasibility, safety, and induction of systemic intracranial T-cell patients glioblastoma multiforme. Experimental Design: Twelve were enrolled into multicohort dose-escalation...
The Scleroderma Lung Study enrolled 158 patients with scleroderma-related interstitial lung disease in a placebo-controlled trial of oral cyclophosphamide (CYC). Although treatment-related benefits pulmonary function, skin scores, and patient-centered outcomes were demonstrated after 1 year therapy, the duration benefit beyond was unclear.A second follow-up performed to determine if these effects persisted stopping treatment.A detailed analysis data obtained over two years study...
Polyclonal convalescent plasma may be obtained from donors who have recovered coronavirus disease 2019 (Covid-19). The efficacy of this in preventing serious complications outpatients with recent-onset Covid-19 is uncertain.
<h3>Objective</h3> To assess survival and identify predictors of in patients with systemic sclerosis-interstitial lung disease (SSc-ILD) who participated the Scleroderma Lung Studies (SLS) I II. <h3>Methods</h3> SLS randomised 158 SSc-ILD to 1 year oral cyclophosphamide (CYC) vs placebo. II 142 CYC followed by placebo 2 years mycophenolate mofetil. Counting process Cox proportional hazard modelling identified variables associated long-term mortality Internal validation was performed using...
Abstract The ability of dendritic cells (DC) to initiate immune responses in naive T is dependent upon a maturation process that allows the develop their potent Ag-presenting capacity. Although immature DC can be derived vitro by treatment peripheral blood monocytes with GM-CSF and IL-4, additional signals such as those provided TNF-α, CD40 ligand, or LPS are required for complete maximum APC function. Because we recently found microbial lipoproteins activate through Toll-like receptor (TLR)...
Abstract The diverse roles of interferon-α (IFN-α) in regulating the immune response to infectious agents suggested that it might affect dendritic cell (DC) development. Peripheral blood mononuclear cells cultured with IFN-α and granulocyte-macrophage colony-stimulating factor (GM-CSF) developed a morphology expressed high levels class I II human leukocyte antigens (HLA), B7 costimulatory molecules, adhesion proteins, CD40. Elevated DC expression B7-2 HLA-DR was observed increasing...
Abstract In this study, we show that Δ-9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, suppresses host immune reactivity against lung cancer. two different weakly immunogenic murine cancer models, intermittent administration THC (5 mg/kg, four times/wk i.p. for 4 wk) led to accelerated growth tumor implants compared with treatment diluent alone. contrast our findings in immunocompetent mice, did not affect tumor-bearing SCID mice. The inhibitory cytokines, IL-10...
Abstract Mammalian Toll-like receptors (TLRs) are required for cell activation by bacterial lipoproteins (bLP) and LPS. Stimulation of monocytes with bLP LPS results in a TLR-dependent induction immunomodulatory genes leading to the production pro-inflammatory cytokines. In this paper, we compared expression response TLRs on dendritic cells (DC). TLR2, but not TLR4, was detected peripheral blood DC, lymphoid tissue CD1a+ DC as well vitro monocyte-derived DC. Upon stimulation or LPS, produced...
Abstract Tumors produce a number of immunosuppressive factors that block the maturation CD34+ stem cells into dendritic (DC). We hypothesized tumors might also interfere with and/or function human monocyte-derived DC. In contrast to cells, we found CD14+ responded tumor culture supernatant (TSN) by increasing expression APC surface markers, up-regulating nuclear translocation RelB, and developing allostimulatory activity. Although displaying these characteristics mature DC, TSN-exposed DC...
Use of marijuana and cocaine is on the rise in United States. Although pulmonary toxicity from these drugs has occasionally been reported, little known about their effects lung microenvironment. We evaluated function alveolar macrophages (AMs) recovered lungs nonsmokers habitual smokers either tobacco, marijuana, or crack cocaine. AMs were deficient ability to phagocytose Staphylococcus aureus (p < 0.01). users also severely limited kill both bacteria tumor cells Studies using N...
Forty healthy young subjects, ages 20 to 49 yr, underwent videobronchoscopy, mucosal biopsy, and bronchial lavage evaluate the airway inflammation produced by habitual smoking of marijuana and/or tobacco. Videotapes were graded in a blinded manner for central erythema, edema, secretions using modified visual bronchitis index. The index scores significantly higher smokers (MS), tobacco (TS), combined marijuana/tobacco (MTS), than nonsmokers (NS). As pathologic correlate, biopsies evaluated...
Abstract The combination of granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) induces the growth antigen-presenting cells (APC) from adherent peripheral blood leukocytes. These have been characterized as dendritic (DC), yet many questions exist regarding their relationship to other DC populations nature progenitors. To address these issues, we utilized a immunomagnetic depletion, cell sorting, culture isolate four distinct APC populations; macrophages...
Rationale: The presence of inflammatory cells on bronchoalveolar lavage is often used to predict disease activity and the need for therapy in systemic sclerosis–associated interstitial lung disease.Objectives: To evaluate whether cellularity identifies distinct subsets and/or predicts cyclophosphamide responsiveness.Methods: Patients underwent baseline high-resolution computed tomography as part a randomized placebo-controlled trial versus placebo (Scleroderma Lung Study) determine effect...
Patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) are thought to have the greatest decline in function (forced vital capacity [FVC]% predicted) early years after onset. The aim of this study was assess natural history FVC% predicted patients receiving placebo Scleroderma Lung Study and evaluate possible factors for cohort enrichment future therapeutic trials.Patients randomized receive (n=79) were divided into 3 groups based on duration SSc (0-2 years, 2-4 >4...
To compare mycophenolate mofetil (MMF) with placebo for the treatment of systemic sclerosis (SSc)-related interstitial lung disease (ILD).
To identify baseline characteristics of patients with scleroderma-related interstitial lung disease (SSc-ILD) that could serve as predictors the most favorable response to 12-month treatment oral cyclophosphamide (CYC).Regression analyses were retrospectively applied Scleroderma Lung Study data in order correlated absolute change forced vital capacity (FVC) (% predicted values) and placebo-adjusted % FVC over time (the CYC effect).Completion arm was associated a improvement 2.11% at 12...
Background: The extent of lung involvement visualized by high-resolution computed tomography (HRCT) is a predictor decline in forced vital capacity (FVC) scleroderma-interstitial disease.Our objective was to evaluate the performance three different HRCT-defined staging systems Scleroderma Lung Study I (SLS I) over 1-year period. Methods:We assessed two visual semiquantitative scores: maximum fibrosis score (MaxFib, zone maximal involvement) and assessment total (TLI) as proposed Goh Wells.In...
To assess the reliability and minimal clinically important differences (MCID) for FVC% predicted in Scleroderma Lung Study I II.
The Scleroderma Lung Study II (SLS II) demonstrated significant improvements in pulmonary function and dyspnea at 24 months compared with baseline when patients symptomatic scleroderma-related interstitial lung disease (SSc-ILD) were treated either cyclophosphamide for 1 year (followed another on placebo) or mycophenolate mofetil 2 years a randomized, double-blind clinical trial. Physiologic outcomes of SLS have been published previously.The aim the study was to assess changes from extent...
Study Design. Retrospective review of prospectively collected data. Objective. To assess the value deformity angular ratio (DAR, maximum Cobb measurement divided by number vertebrae involved) in evaluating severity spinal deformity, and predicting risk neurologic deficit posterior vertebral column resection (PVCR). Summary Background Data. Although literature has demonstrated that PVCR patients achieved excellent outcomes, it is still high neurologically. This study, to our knowledge,...