Heerfordt’s Syndrome : An interesting and under-recognised manifestation of sarcoidosis

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Evidence of platelet activation in multiple sclerosis

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Neuronal and astrocytic interactions modulate brain endothelial properties during metabolic stresses of in vitro cerebral ischemia

Neurovascular and gliovascular interactions significantly affect endothelial phenotype. Physiologically, brain endothelium attains several of its properties by its intimate association with neurons and astrocytes. However, during cerebrovascular pathologies such as cerebral ischemia, the uncoupling of neurovascular and gliovascular units can result in several phenotypical changes in brain endothelium. The role of neurovascular and gliovascular uncoupling in modulating brain endothelial properties during cerebral ischemia is not clear. Specifically, the roles of metabolic stresses involved in cerebral ischemia, including aglycemia, hypoxia and combined aglycemia and hypoxia (oxygen glucose deprivation and re-oxygenation, OGDR) in modulating neurovascular and gliovascular interactions are not known. The complex intimate interactions in neurovascular and gliovascular units are highly difficult to recapitulate in vitro. However, in the present study, we used a 3D co-culture model of brain endothelium with neurons and astrocytes in vitro reflecting an intimate neurovascular and gliovascular interactions in vivo. While the cellular signaling interactions in neurovascular and gliovascular units in vivo are much more complex than the 3D co-culture models in vitro, we were still able to observe several important phenotypical changes in brain endothelial properties by metabolically stressed neurons and astrocytes including changes in barrier, lymphocyte adhesive properties, endothelial cell adhesion molecule expression and in vitro angiogenic potential

Alzheimer's disease and HIV associated dementia related genes: I. location and function.

Alzheimer's disease (AD), the most common cause of dementia, has few clinical similarities to HIV-1-associated dementia (HAD). However, genes were identified related among these dementias. Discovering correlations between gene function, expression, and structure in the human genome continues to aid in understanding the similarities between pathogenesis of these two dementing disorders. The current work attempts to identify relationships between these dementias in spite of their clinical differences, based on genomic structure, function, and expression. In this comparative study, the NCBI Entrez Genome Database is used to detect these relationships. This approach serves as a model for future diagnosis and treatment in the clinical arena as well as suggesting parallel pathways of disease mechanisms. Identifying a correlation among expression, structure, and function of genes involved in pathogenesis of these dementing disorders, may assist to understand better their interaction with each other and the human genome

Soluble HLA measurement in saliva and cerebrospinal fluid in Caucasian patients with multiple sclerosis: a preliminary study

BACKGROUND: Measurement of soluble HLA in body fluids has a potential role in assessing disease activity in autoimmune disorders. METHODS: We applied a solid phase, enzyme-linked immunoassay to measure soluble HLA class I (sHLA-I) and class II (sHLA-II) molecules in the saliva and cerebrospinal fluid (CSF) in 13 untreated patients with relapsing-remitting form of multiple sclerosis (MS). For comparison purposes, we also studied saliva from 53 healthy subjects. RESULTS: Saliva from normal controls had detectable sHLA-I levels in 41 of 53 individuals studied, with values ranging from 9–100 ng/ml (mean = 41 ± 2.8 ng/ml). sHLA-I was undetectable in the saliva in 11 of 13 MS patients, and in none of the CSF specimens. In contrast, mean sHLA-II concentration in the saliva of MS patients was significantly increased compared to controls (386 ± 52 unit/ml vs. 222 ± 18.4 unit/ml, t = 8.68, P < 0.005). The mean CSF sHLA-II level (369 ± 16 unit/ml) was equivalent to the mean sHLA-II concentration measured in saliva (mean = 386 ± 52 unit/ml) (P = 0.7). In patients with brain magnetic resonance imaging (MRI) enhancing lesions (n = 5), reflective of more active disease, CSF sHLA-II averaged 356 ± 26 unit/ml compared to 380 ± 51 in saliva. Similarly, in patients with non-enhancing lesions (n = 8), CSF sHLA-II averaged 377 ± 18 unit/ml compared to 390 ± 77 unit/ml in saliva. Thus, the mean sHLA-II concentration in saliva and CSF was essentially equivalent for MS patients with or without enhancing plaques. CONCLUSION: Our data suggest that the measurement of soluble HLA in saliva, specifically sHLA-II, correlates with the level found in the CSF. Therefore, if sHLA correlates with disease activity in MS, as has been proposed, saliva measurements provide a noninvasive correlate of CSF measurement

Interferon-β1a reduces plasma CD31+ endothelial microparticles (CD31+EMP) in multiple sclerosis

BACKGROUND: A correlation between plasma CD31+ endothelial microparticles (CD31+EMP) levels and clinical, as well as brain MRI activity, in multiple sclerosis (MS) patients has been previously reported. However, the effect(s) of treatment with interferon-β1a (IFN-β1a) on plasma levels of CD31+EMP has not been assessed. In a prospective study, we measured plasma CD31+EMP levels in 30 patients with relapsing-remitting MS. METHODS: Using flow cytometry, in a blinded study, we measured plasma CD31+EMP in 30 consecutive patients with relapsing-remitting MS (RRMS) prior to and 4, 12, 24 and 52 weeks after initiation of intramuscular therapy with interferon-β1a (IFN-β1a), 30 micrograms weekly. At each visit, clinical examination was performed and expanded disability status scale (EDSS) scores were assessed. RESULTS: Plasma levels of CD31+EMP were significantly reduced from 24 through 52 weeks following initiation of treatment with IFN-β1a. CONCLUSION: Our data suggest that serial measurement of plasma CD31+EMP levels may be used as a surrogate marker of response to therapy with INF-β1a. In addition, the decline in plasma levels of CD31+EMP further supports the concept that IFN-β1a exerts stabilizing effect on the cerebral endothelial cells in pathogenesis of MS

Molecular epigenetics, chromatin, and NeuroAIDS/HIV: Immunopathological implications

Epigenetics studies factors related to the organism and environment that modulate inheritance from generation to generation. Molecular epigenetics examines non-coding DNA (ncdDNA) vs. coding DNA (cdDNA), and pertains to every domain of physiology, including immune and brain function. Molecular cartography, including genomics, proteomics, and interactomics, seeks to recognize and to identify the multi-faceted and intricate array of interacting genes and gene products that characterize the function and specialization of each individual cell in the context of cell-cell interaction, tissue, and organ function. Molecular cartography, epigenetics, and chromatin assembly, repair and remodeling (CARR), which, together with the RNA interfering signaling complex (RISC), is responsible for much of the control and regulation of gene expression, intersect

Troglitazone, a PPAR-γ activator prevents endothelial cell adhesion molecule expression and lymphocyte adhesion mediated by TNF-α

BACKGROUND: Cytokine mediated induction of the mucosal addressin cell adhesion molecule-1(MAdCAM-1) expression is associated with the onset and progression of inflammatory bowel disease (IBD). RESULTS: Using western blotting and cell-based ELISA, we show in this study that troglitazone, an activator of the peroxisome proliferator-activated receptor-γ (PPAR-γ), widely used in the treatment of diabetes, has as well recently been highlighted as protective in models of inflammation and cancer. We found that troglitazone (10–40 μM), significantly reduced the TNF-α (1 ng/ml) mediated induction of endothelial MAdCAM-1 in a dose-dependent manner, achieving a 34.7% to 98.4% reduction in induced MAdCAM-1. Trogliazone (20μM) reduced TNF-α induced VCAM-1, ICAM-1 and E-selectin expression. Moreover, troglitazone significantly reduced α4β7-integrin dependent lymphocyte adhesion to TNF-α cultured endothelial cells. CONCLUSIONS: These results suggest that PPAR-γ agonists like troglitazone may be useful in the clinical treatment of IBD

Molecular epigenetics, chromatin, and NeuroAIDS/HIV: Translational implications

We describe current research that applies epigenetics to a novel understanding of the immuno-neuropathogenesis of HIV-1 viral infection and NeuroAIDS. We propose the hypothesis that HIV-1 alters the structure-function relationship of chromatin, coding DNA and non-coding DNA, including RNA transcribed from these regions resulting in pathogenesis in AIDS, drug abuse, and NeuroAIDS. We discuss the general implications of molecular epigenetics with special emphasis on drug abuse, bar-codes, pyknons, and miRNAs for translational and clinical research. We discuss the application of the recent recursive algorithm of biology to this field and propose to synthesize the Genomic and Epigenomic views into a holistic approach of HoloGenomics