👤 Javad Rasouli

Antigen (Ag)-specific tolerance induction by intravenous (i. v.) injection of high-dose auto-Ags has been explored for therapy of autoimmune diseases, including multiple sclerosis (MS). It is thought that the advantage of such Ag-specific therapy over non-specific immunomodulatory treatments would be selective suppression of a pathogenic immune response without impairing systemic immunity, thus avoiding adverse effects of immunosuppression. Auto-Ag i.v. tolerance induction has been extensively studied in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and limited clinical trials demonstrated that it is safe and beneficial to a subset of MS patients. Nonetheless, the mechanisms of i.v. tolerance induction are incompletely understood, hampering the development of better approaches and their clinical application. Here, we describe a pathway whereby auto-Ag i.v. injected into mice with ongoing clinical EAE induces interferon-gamma (IFN-γ) secretion by auto-Ag-specific CD4 Show less

To determine altered gene expression profiles in subcutaneous adipose and skeletal muscle from nondiabetic, insulin-resistant individuals compared with insulin-sensitive individuals matched for BMI. A total of 62 nondiabetic individuals were chosen for extremes of insulin sensitivity (31 insulin-resistant and 31 insulin-sensitive subjects; 40 were European American and 22 were African American) and matched for age and obesity measures. Global gene expression profiles were determined and compared between ethnic groups and between insulin-resistant and insulin-sensitive participants individually and using gene-set enrichment analysis. African American and European American subjects differed in 58 muscle and 140 adipose genes, including many inflammatory and metabolically important genes. Peroxisome proliferator-activated receptor γ cofactor 1A (PPARGC1A) was 1.75-fold reduced with insulin resistance in muscle, and fatty acid and lipid metabolism and oxidoreductase activity also were downregulated. Unexpected categories included ubiquitination, citrullination, and protein degradation. In adipose, highly represented categories included lipid and fatty acid metabolism, insulin action, and cell-cycle regulation. Inflammatory genes were increased in European American subjects and were among the top Kyoto Encyclopedia of Genes and Genomes pathways on gene-set enrichment analysis. FADS1, VEGFA, PTPN3, KLF15, PER3, STEAP4, and AGTR1 were among genes expressed differentially in both adipose and muscle. Adipose tissue gene expression showed more differences between insulin-resistant versus insulin-sensitive groups than the expression of genes in muscle. We confirm the role of PPARGC1A in muscle and show some support for inflammation in adipose from European American subjects but find prominent roles for lipid metabolism in insulin sensitivity independent of obesity in both tissues. Show less

Identification of casual mutations in Hereditary Multiple Exostoses (HME) is important because of similar conditions in which multiple exostoses occur. Therefore mutation analysis can help to confirm the clinical diagnosis and to improve the management of therapy. HME is an inherited disorder of bone growth. HME can be referred to by various names such as Heredity Multiple Exostoses, Hereditary Multiple Osteochondromata, Multiple Carthaginous Exostoses, etc. People who have HME grow exostoses, or bony bumps, on their bones which can vary in size, location and number depending on the individual. HME is inherited in an autosomal dominant manner with an estimated prevalence of 1/50,000 in western countries. At least three loci (EXT1, EXT2 and EXT3) thought to be involved in this skeletal disease. Approximately 90% of affected families possess mutations in the coding regions of EXT1 and EXT2 genes and the majority of these mutations cause loss of function. EXT1 and EXT2 genes encode related members of a putative tumor suppressor family. In this first report from Iran we identified a frame shift mutation (1100-1101 insA) in exon 3 of EXT1 gene in a family being suspicious of HME. This mutation leads to a premature stop codon and previously not described. Additionally, we have found an unreported silent mutation in the exon six of EXT1 gene with uncertain significance. Show less