Modulation of B-cell endoplasmic reticulum calcium homeostasis by Epstein-Barr virus Latent Membrane Protein-1

Background  

Calcium signaling plays an important role in B lymphocyte survival and activation, and is critically dependent on the inositol-1,4,5-tris-phosphate-induced release of calcium stored in the endoplasmic reticulum (ER). Calcium is accumulated in the ER by Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes), and therefore these enzymes play an important role in ER calcium homeostasis and in the control of B of cell activation. Because Epstein-Barr virus (EBV) can immortalize B cells and contributes to lymphomagenesis, in this work the effects of the virus on SERCA-type calcium pump expression and calcium accumulation in the endoplasmic reticulum of B cells was investigated.     

Biological monitoring of environmental exposure to polycyclic aromatic hydrocarbons in subjects living in the vicinity of a creosote impregnation plant

Objective: This study was undertaken to evaluate the environmental exposure to polycyclic aromatic hydrocarbons (PAHs) in nonsmoking adult subjects living in the vicinity of a creosote impregnation plant in Delson, Canada. Urinary metabolites of naphthalene, α- and β-naphthol, and pyrene metabolite 1-hydroxypyrene (1-OHP), were used as biomarkers of exposure. Methods: Morning and evening urine samples were collected in mid-August from 30 exposed individuals living at a distance of 50–360 m downwind of the plant and from a control group in the adjoining municipality residing at a distance of 1.9–2.7 km upwind of the plant. Metabolites were measured by gas chromatography/mass spectrometry. Results: Excretion values of α- and β-naphthol were significantly higher in the exposed group than in controls (P < 0.04), after accounting for possible confounding variables by multivariate analyses. The respective geometric mean concentrations (5th and 95th percentiles) of α-naphthol for the exposed and nonexposed groups were 2.04 (0.55–6.00) and 1.37 (0.39–7.02) μmol/mol creatinine for evening samples, and 2.49 (0.77–8.43) and 1.17 (0.37–6.88) μmol/mol creatinine for morning samples. Corresponding values for β-naphthol were 1.78 (0.82–3.67) and 1.36 (0.63–5.07) μmol/mol creatinine for evening samples, and 1.94 (1.03–4.96) and 1.08 (0.49–5.05) μmol/mol creatinine for morning samples. On the other hand, no significant difference in 1-OHP excretion was observed between the exposed and the control group (P>0.5). The respective geometric mean concentrations (5th and 95th percentiles) of 1-OHP for these groups were 0.05 (0.01–0.17) and 0.06 (0.01–0.48) μmol/mol creatinine for evening samples, and 0.05 (0.02–0.12) and 0.05 (0.01–0.42) μmol/mol creatinine for morning samples. Conclusions: The measurement of α- and β-naphthol urinary concentrations appears to be an approach sufficiently sensitive to reveal differences in low exposure levels of volatile PAHs due to creosote impregnation plant emissions. However, uptake of pyrene due to the plant was too small to contribute significantly to 1-OHP excretion. Received: 13 June 2000 / Accepted: 21 April 2001     

Flow Cytometric Microsphere-Based Immunoassay: Analysis of Secreted Cytokines in Whole-Blood Samples from Asthmatics

The ability of flow cytometry to resolve multiple parameters was used in a microsphere-based flow cytometric assay for the simultaneous determination of several cytokines in a sample. The flow cytometer microsphere-based assay (FMBA) for cytokines consists of reagents and dedicated software, specifically designed for the quantitative determination of cytokines. We have made several improvements in the multiplex assay: (i) dedicated software specific for the quantitative multiplex assay that processes data automatically, (ii) a stored master calibration curve with a two-point recalibration to adjust the stored curve periodically, and (iii) an internal standard to normalize the detection step in each sample. Overall analytical performance, including sensitivity, reproducibility, and dynamic range, was investigated for interleukin-4 (IL-4), IL-6, IL-10, IL-12, gamma interferon (IFN-γ), and tumor necrosis factor alpha. These assays were found to be reproducible and accurate, with a sensitivity in the picograms-per-milliliter range. Results obtained with FMBA correlate well with commercial enzyme-linked immunosorbent assay data (r > 0.98) for all cytokines assayed. This multiplex assay was applied to the determination of cytokine profiles in whole blood from atopic and nonatopic patients. Our results show that atopic subjects' blood produces more IL-4 (P = 0.003) and less IFN-γ (P = 0.04) than the blood of nonatopic subjects. However, atopic asthmatic subjects' blood produces significantly more IFN-γ than that of atopic nonasthmatic subjects (P = 0.03). The results obtained indicate that the FMBA technology constitutes a powerful system for the quantitative, simultaneous determination of secreted cytokines in immune diseases.     

Dairy in Adulthood: From Foods to Nutrient Interactions on Bone and Skeletal Muscle Health

The risk of fragility fractures exponentially increases with aging. Reduced mass and strength of both bone in osteoporosis and skeletal muscle in sarcopenia play a key role in the age-related incidence of fragility fractures. Undernutrition is often observed in the elderly, particularly in those subjects experiencing osteoporotic fractures, more likely as a cause than a consequence. Calcium (Ca), inorganic phosphate (Pi), vitamin D, and protein are nutrients that impact bone and skeletal muscle integrity. Deficiency in the supply of these nutrients increases with aging. Dairy foods are rich in Ca, Pi, and proteins and in many countries are fortified with vitamin D. Dairy foods are important souces of these nutrients and go a long way to meeting the recommendations, which increase with aging. This review emphaszes the interactions between these 4 nutrients, which, along with physical activity, act through cellular and physiological pathways favoring the maintenance of both bone and skeletal muscle structure and function.