Biomedical subjects

Michael Gurevich

Publications and source records attributed to Michael Gurevich.

3 recordsLinked to original sources

PubMed2005

Unique gene expression patterns in human T-cell lines generated from multiple sclerosis patients by stimulation with a synthetic MOG peptide.

Multiple sclerosis (MS) is an autoimmune disease where T-cells activated against myelin antigens are involved in myelin destruction. Yet, healthy subjects also harbor T-cells responsive to myelin antigens, suggesting that MS patient-derived autoimmune T-cells might bear functional differences from T-cells derived from healthy individuals. We addressed this issue by analyzing gene expression patterns of myelin oligodendrocytic glycoprotein (MOG) responsive T-cell lines generated from MS patients and healthy subjects. We identified 150 transcripts that were differentially expressed between MS patients and healthy controls. The most informative 43 genes exhibited > 1.5-fold change in expression level. Eighteen genes were upregulated including BCL2, lifeguard, IGFBP3 and VEGF. Twenty five genes were down-regulated, including apoptotic activators like TNF and heat shock protein genes. This gene expression pattern was unique to MOG specific T-cell lines and was not expressed in T-cell lines reactive to tetanus toxin (TTX). Our results indicate that activation in MS that promotes T-cell survival and expansion, has its own state and that the unique gene expression pattern that characterize autoreactive T-cells in MS represent a constellation of factors in which the chronicity, timing and accumulation of damage make the difference between health and disease.

Base Sequence↗

PubMed2004

Blood transcriptional signatures of multiple sclerosis: unique gene expression of disease activity.

Multiple sclerosis (MS) is a central nervous system disease with an unpredictable course and outcome. Peripheral blood mononuclear cells (PBMCs) are involved in the disease pathogenesis and induce active demyelination. Using oligonucleotide microarrays, we identified a statistically significant transcriptional signature of 1,109 genes in PBMCs from 26 MS patients, irrespective of disease activation state or immunomodulatory treatment. This signature contains genes that implicate underlying processes involved in MS pathogenesis including T-cell activation and expansion, inflammation, and apoptosis. Another transcriptional signature of 721 genes involved in cellular recruitment, epitope spreading, and escape from regulatory immune surveillance identified MS patients in acute relapse compared with remission. Our results offer new opportunity for understanding the mechanisms involved in MS and indicate that gene expression patterns in PBMCs contain information about a remote-target disease process that may be useful for diagnosis and future tailoring of therapeutic strategies for MS.

Adjuvants, Immunologic↗

PubMed2002

Mutagenicity and in vivo toxicity of combined particulate and semivolatile organic fractions of gasoline and diesel engine emissions.

Exposure to engine emissions is associated with adverse health effects. However, little is known about the relative effects of emissions produced by different operating conditions, fuels, or technologies. Rapid screening techniques are needed to compare the biological effects of emissions with different characteristics. Here, we examined a set of engine emission samples using conventional bioassays. The samples included combined particulate material and semivolatile organic compound fractions of emissions collected from normal- and high-emitter gasoline and diesel vehicles collected at 72 degrees F, and from normal-emitter groups collected at 30 degrees F. The relative potency of the samples was determined by statistical analysis of the dose-response curves. All samples induced bacterial mutagenicity, with a 10-fold range of potency among the samples. Responses to intratracheal instillation in rats indicated generally parallel rankings of the samples by multiple endpoints reflecting cytotoxic, inflammatory, and lung parenchymal changes, allowing selection of a more limited set of parameters for future studies. The parameters selected to assess oxidative stress and macrophage function yielded little useful information. Responses to instillation indicated little difference in potency per unit of combined particulate material and semivolatile organic compound mass between normal-emitter gasoline and diesel vehicles, or between emissions collected at different temperatures. However, equivalent masses of emissions from high-emitter vehicles of both types were more potent than those from normal-emitters. While preliminary in terms of assessing contributions of different emissions to health hazards, the results indicate that a subset of this panel of assays will be useful in providing rapid, cost-effective feedback on the biological impact of modified technology.

Air Pollutants↗