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Biomedical subjects

Ariel Miller

Publications and source records attributed to Ariel Miller.

29 records · Page 2Linked to original sources
PubMed2004

Cognitive strategies application of multiple sclerosis patients.

When performing a novel task, people need to generate and apply a working strategy. The application of an appropriate working strategy enables patients with cognitive impairment (CI) to perform tasks efficiently, which in turn makes it easier to meet the challenges of daily life tasks. We investigated the strategy application abilities (SAA) of multiple sclerosis (MS) patients and compared these results with data based on healthy subjects' performance. Seventy-six patients performed a Strategy Application Test (SAT) along with other cognitive tests, and completed depression, fatigue, and activity of daily living (ADL) questionnaires. Our results indicated that 76% of the MS patients included had impaired SAA, and that this impairment was not correlated with their depression, fatigue, Expanded Disability Severity Scale (EDSS), or ADL. These findings may have important implications for the understanding of the capability of MS patients to cope with nonroutine tasks, as well as for the potential of future implementation of cognitive rehabilitation in improving the SAA of patients with MS or other cognitive disorders.

Activities of Daily Living↗
PubMed2003

Expression of matrix metalloproteinases, sICAM-1 and IL-8 in CSF from children with meningitis.

The combined expression of the inflammatory mediators, matrix metalloproteinases (MMPs), soluble form of intracellular adhesion molecule ICAM-1 (sICAM-1) and interleukin (IL)-8, was evaluated in children infected with bacterial or viral meningitis. MMP-2 and IL-8 were detected in all CSF samples and were enhanced in both bacterial and viral infected samples, compared to those from control children. The expression of MMP-9 as well as sICAM-1 was not detected in control CSF while observed in viral infected and further elevated in bacterial infected samples. This pilot study supports a role for MMPs, IL-8 and sICAM in infectious meningitis and suggests further research to determine their possible use as biomarkers for various forms of meningeal infection as well as the use of their specific antagonists as potential therapeutic agents for central nervous system (CNS) inflammatory processes.

Biomarkers↗
PubMed2003

The 'immunological-synapse' at its APC side in relapsing and secondary-progressive multiple sclerosis: modulation by interferon-beta.

Reciprocal interactions between T cells and antigen-presenting cells (APCs) within the 'Immunological-Synapse' (IS) govern immune cell autoreactivity in multiple sclerosis (MS). The present study examined the expression of a range of co-stimulatory molecules: CD40, CD54, CD80, CD86 and HLA-DR, on the cell-surface of CD14(+) peripheral blood monocytes (PBM) from relapsing-remitting (RR) and secondary-progressive (SP)-MS patients, prior to and during 1 year of Interferon (IFN)-beta-1a (Rebif(R)) therapy. Prior to treatment, patients from both MS subtypes expressed elevated CD80 and reduced CD40 levels in comparison to controls. CD86 expression was significantly reduced in SP compared to RR patients and controls. IFN-beta therapy led to a significant reduction in the expression of CD54 and CD80 in both groups of patients as well as to elevation of CD40 and CD86 expression in SP patients. These results confirm IFN-mediated modulation of the APC surface within the immunological-synapse and implicate CD80 and CD86 as targets for interventional therapies in MS as well as other Th1-mediated autoimmune diseases.

Adjuvants, Immunologic↗
PubMed2002

Regulation of endothelial matrix metalloproteinase-2 by hypoxia/reoxygenation.

Among the consequences resulting from the exposure of endothelial cells (ECs) to ischemia/reperfusion is angiogenesis, involving degradation of vascular basement membrane and extracellular matrix. Matrix metalloproteinase (MMP)-2, a member of the MMP family, partakes in this process. MMP-2, secreted as a proenzyme, undergoes activation through interaction with membrane type (MT)1-MMP and the endogenous tissue inhibitor of MMPs (TIMP)-2. Although hypoxia and reoxygenation (H/R) are major constituents of ischemia/reperfusion processes, their direct effects on endothelial MMP-2 have been scarcely investigated. This study examined the in vitro effects of H/R on human macrovascular ECs (EAhy 926). The level of MMP-2 mRNA (Northern blot) and protein (zymography, ELISA) and the mRNA of its activator (MT1-MMP) and inhibitor (TIMP-2) were analyzed. Short (6-hour) hypoxia inhibited the mRNA expression of MMP-2, MT1-MMP, and TIMP-2, culminating in reduced latent and active MMP-2 protein. Prolonged (24-hour) hypoxia further suppressed MT1-MMP and TIMP-2 mRNA, whereas it enhanced MMP-2 mRNA and enzyme secretion (after 48-hour hypoxia). Reoxygenation did not influence the inhibited TIMP-2 but upregulated MMP-2 and MT1-MMP mRNA expression, leading to enhanced secretion of active MMP-2 protein. These results demonstrate H/R-mediated modulation of EC MMP-2 at both transcriptional and posttranscriptional levels. Prolonged hypoxia of ECs appears to enhance MMP-2 production and secretion, whereas reoxygenation further increases its level. These H/R-mediated effects on MMPs have the potential of enabling EC migration and possible angiogenesis.

Blotting, Northern↗
PubMed2002

Modulation of monocytes matrix metalloproteinase-2, MT1-MMP and TIMP-2 by interferon-gamma and -beta: implications to multiple sclerosis.

Recent findings have implicated the activity of matrix metalloproteinases (MMPs) in the pathogenesis of multiple sclerosis (MS), while in vivo interferon (IFN)-beta treatment was demonstrated to suppress MMPs. In the present study, the effects mediated by IFN-gamma and IFN-beta on the mRNA and protein expression of MMP-2, its physiological activator, MT1-MMP and its endogenous inhibitor, TIMP-2, by monocytes were evaluated in vitro. The results point to the significance of IFNs in modulating MMPs/tissue inhibitors of MMPs (TIMPs) expression, and support the possibility that the therapeutic effects of IFN-beta may be, in part, due to induction of a shift from "pro-" to "anti-proteolytic" pattern of MMPs and TIMPs expression.

Dose-Response Relationship, Drug↗
PubMed2002

Inorganic lead enhances cytokine-induced elevation of matrix metalloproteinase MMP-9 expression in glial cells.

Inorganic lead (Pb) is a ubiquitous environmental contaminant that produces a variety of deleterious effects in the central nervous system (CNS). Matrix metalloproteinases (MMPs), specifically MMP-9, induced by inflammatory cytokines, are increasingly being implicated in CNS pathology. The present study demonstrates that low concentrations of either pro-inflammatory cytokines (TNF-alpha and IL-1beta) or Pb did not influence the MMP-9 expression in a glial cell line (C6) when added separately. However, combined administration of Pb and cytokines induced a marked synergized elevation of MMP-9 expression in spite of a reduction in the number of glial cells. These results demonstrate a possible new mechanism by which Pb may induce neuropathological processes.

Animals↗
PubMed2002

The role of IL-18 and IL-12 in the modulation of matrix metalloproteinases and their tissue inhibitors in monocytic cells.

The matrix metalloproteinases (MMP) are enzymes crucial for the physiological patrol as well as pathological chemotaxis of immune cells to target tissues. The present study examined differential effects of pro-inflammatory [IL-18, IL-12 and tumor necrosis factor (TNF)-alpha] versus anti-inflammatory (IL-4) cytokines on the modulation of MMP and their endogenous tissue inhibitors (TIMP) expression in the U937 cell line. IL-18 and IL-12 separately and synergistically enhanced MMP-2, while TNF-alpha led to the elevation of MMP-9. All pro-inflammatory cytokines enhanced MT1-MMP expression and IL-4 suppressed TNF-alpha-induced MMP-9 expression. This study demonstrated that elevated IL-18 and IL-12, and related pro-inflammatory activity, may be associated with aberrant MMP activity, suggesting modulation of MMP expression using IL-12 and IL-18 antagonists as future therapeutic strategies to attenuate inflammatory and autoimmune disorders.

Cell Line↗
PubMed2002

Immunological indicators of disease activity and prognosis in multiple sclerosis.

The need to ensure an accurate diagnosis and proper treatment for multiple sclerosis patients, considering the various clinical and immunopathological subtypes of the disease, requires the identification of biomarkers that measure disease activity and predict the course of disease development in individual patients. Moreover, the identification of effective indicators will lead not only to optimized patient treatment but also to the development of better tools for evaluating clinical trials. Recent studies focusing on the identification of possible immunological markers in multiple sclerosis will be reviewed.

Antigens, Surface↗
PubMed2002

Pharmacogenetic Development of Personalized Medicine: Multiple Sclerosis Treatment as a Model.

The goal of pharmacogenetics is to identify "genetic fingerprints" that may predict a patient's response to pharmaceutical treatment. The use of pharmacogenetics replaces the trial-and-error strategy, which governs much of our clinical decision-making regarding treatment allocation in current medical practice, with individually tailored therapy. We review a pharmacogenetic research model, which implements high-throughput single nucleotide polymorphism technology to establish the correlation between drug-responsiveness and genetic polymorphisms of Copaxone(R)-treated multiple sclerosis patients. Implementation of similar pharmacogenetic approaches may promote the development of personalized medicine in multiple sclerosis as well as in other diseases. (c) 2002 Prous Science. All rights reserved.

Journal Article↗