Relationship of DNA methylation and gene expression in idiopathic pulmonary fibrosis.

Rationale: Idiopathic pulmonary fibrosis (IPF) is an untreatable and often fatal lung disease that is increasing in prevalence and is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control gene expression and are likely to regulate the IPF transcriptome.

Objectives: To identify methylation marks that modify gene expression in IPF lung.

Methacholine challenge testing: improved patient comfort with a 2-tiered protocol.

Background: The methacholine challenge test (MCT) is a test of bronchial hyperreactivity used as an aid in the diagnosis of asthma. MCT results are reported as the provocation concentration at which the forced expiratory volume in 1 second (FEV1) decreases 20% (PC20). The requirement for a 20% or greater decrease in FEV1 results in precipitous decreases in FEV1 in some patients.

Profibrotic role of miR-154 in pulmonary fibrosis.

In this study, we explored the regulation and the role of up-regulated microRNAs in idiopathic pulmonary fibrosis (IPF), a progressive interstitial lung disease of unknown origin. We analyzed the expression of microRNAs in IPF lungs and identified 43 significantly up-regulated microRNAs. Twenty-four of the 43 increased microRNAs were localized to the chromosome 14q32 microRNA cluster.

Attempts at suppression of amyloidogenesis in a mouse model by a variety of anti-inflammatory agents.

Objective: The mainstay of AA amyloidosis prevention and treatment is suppression of inflammation. In the present study we have tried to determine the efficacy of a variety of anti-inflammatory agents at suppressing AA amyloidosis in a mouse model of the disease.

Methods: AA amyloidosis was induced in Swiss male mice using amyloid enhancing factor and AgNO(3).

Global methylation patterns in idiopathic pulmonary fibrosis.

Background: Idiopathic Pulmonary Fibrosis (IPF) is characterized by profound changes in the lung phenotype including excessive extracellular matrix deposition, myofibroblast foci, alveolar epithelial cell hyperplasia and extensive remodeling. The role of epigenetic changes in determining the lung phenotype in IPF is unknown. In this study we determine whether IPF lungs exhibit an altered global methylation profile.

Interferon-alpha as a treatment modality for colchicine- resistant familial Mediterranean fever.

Objective: Previous reports on interferon-alpha (IFN-alpha) were conflicting with respect to its efficacy in familial Mediterranean fever (FMF) refractory to colchicine treatment. We investigated the effect of IFN-alpha in patients with colchicine-resistant FMF.

Methods: In a prospective, patient self-controlled, open-label study evaluating the safety and efficacy of IFN-alpha in patients with FMF with a severe phenotype, refractory to intensified (oral plus intravenous) colchicine therapy, we advised patients to subcutaneously inject IFN-alpha, 3 million international units, at the onset of the FMF attack.

A single testing of serum amyloid a levels as a tool for diagnosis and treatment dilemmas in familial Mediterranean fever.

Objectives: In a significant proportion of patients with familial Mediterranean fever (FMF), serum amyloid A (SAA) remains elevated during attack-free periods, thereby increasing the risk of developing amyloidosis. The aim of the study was to determine various correlates of elevated SAA and evaluate the role of SAA measurement in the diagnosis and management of FMF.

Methods: We reviewed the medical files of all 204 patients from our FMF center in whom SAA measurements were performed.