IL-1β increases intracellular calcium through an IL-1 type 1 receptor mediated mechanism in C6 astrocytic cells

Interleukin-1β (IL-1β) is a cytokine that regulates a variety of biological processes. In addition to its traditional role in the immune system, IL-1β plays an integral role in neural-immune and developmental processes in the nervous system. The pleiotropic ability of IL-1β may be due to the activation of different signal transduction mechanisms in specific cell types or under certain cellular conditions. We have previously demonstrated that IL-1β regulates healing and repair in the developing, mammalian nervous system. In the damaged perinatal mouse brain, IL-1β is expressed in astrocytes that change from a stellate to a spindle-shaped morphology. The spindle-shaped astrocytes enclose the wound, separating the healthy from damaged neural tissue. The shape change and subsequent repair processes are IL-1β activity-dependent, acting through the IL-1 type 1 receptor (IL-1R1), as co-application of the IL-1type 1 receptor antagonist protein (IL-1ra) blocks IL-1β induced effects. In the C6 astrocytic cell line, IL-1β induced similar shape changes and upregulated expression of the cytoskeletal protein, glial fibrillary acidic protein (GFAP). Since cytoskeletal changes, as well as specific signal transduction mechanisms, are associated with increases in intracellular calcium ([Ca²⁺]_i), studies were carried out to determine if increases in [Ca²⁺]_i induced by IL-1β occurred through activation of the IL-1R1 in C6 cells. Cells were treated with IL-1β and/or IL-1ra, followed by measurement of relative changes in [Ca²⁺]_i using fura-2 fluorescence imaging methods. IL-1β increased [Ca²⁺]_i levels in a dose and time dependent manner. Treatment with IL-1ra blocked IL-1β induced increases in [Ca²⁺]_i, indicating that IL-1β acts through the IL-1R1. Immunocytochemistry experiments showed that untreated C6 cells normally express IL-1β, IL-1ra, and IL-1R1. Thus, IL-1 system molecules may play a role in normal C6 astrocyte physiology.     

Dietary exposure to Aroclor 1254 alters gene expression in Xenopus laevis frogs

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that contribute to worldwide health problems. Despite data associating PCBs with adverse health effects, decisions to clean up contaminated sites remain controversial. Cleanup decisions are typically based on risk assessment methods that are not sensitive enough to detect subtle changes in health. We have recently shown that gene expression signatures can serve as sensitive molecular biomarkers of exposure and related health effects. Our initial studies were carried out with developing Xenopus laevis tadpoles that were exposed to the PCB mixture Aroclor 1254 (A1254) for 2 days. A1254 was dissolved in dimethyl sulfoxide and added to the aquarium water for rapid loading of PCBs into the tadpole tissue. These studies showed that increases in the expression of specific genes occurred independent of adverse health effects, and decreases in specific genes correlated with the appearance of observable health effects, including decreased survival and gross morphological and behavioral abnormalities. In this report, we extend our previous work to test the use of gene expression signatures as biomarkers in frogs exposed to PCBs through the diet from early tadpole stages through metamorphosis. This work showed that chronic low-dose exposure to A1254 (24 ppm) in food produced tissue levels of 17 ppm and increased gene expression of nerve growth factor and proopiomelanocortin independent of adverse health effects. Exposure to higher doses of A1254 (200 ppm) produced tissue levels of 80 ppm and increased expression of p450 1A1, also, independent of adverse health effects. This work provides further evidence for the use of gene expression changes as biomarkers of exposure to PCBs.     

Exposure to the polychlorinated biphenyl mixture Aroclor 1254 alters melanocyte and tail muscle morphology in developing Xenopus laevis tadpoles

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that have damaging effects on both ecosystem and human health. Numerous studies have shown that exposure to PCBs can alter growth and development of aquatic organisms, including frogs. In this report, developing Xenopus laevis tadpoles were exposed to the PCB mixture Aroclor 1254. Tadpoles were exposed from 5 through 9 d postfertilization to either 0, 1, 10, 50, or 100 ppm Aroclor 1254. Exposure to an acute, high concentration of Aroclor 1254 (10, 50, and 100 ppm) caused statistically significant reductions in survival and body size. In addition, tadpoles exposed to these higher concentrations showed histological abnormalities, including aberrant tail tip, myotomal, and melanocyte morphologies. Described adverse health effects associated with PCB exposure of developing frogs will serve as useful health endpoints in ongoing and future molecular-based studies that correlate health effects with changes in gene expression.     

Jaundice from impacted sediment in a T tube: recognition and treatment.

Encrustation of bile sediment in the proximal limb of an indwelling T tube may occlude the luman and cause jaundice. The cholangiographic appearance of this phenomenon is described. Insertion of a torque cable under fluoroscopic control can successfully disimpact the occlusion, restoring patency and relieving the jaundice.     

Telephone transmission of radiographic images

A new system for telecommunication of radiographic images using readily available telephone transmission circuitry is described. The resulting video images were satisfactory for accurate interpretation in 80% of the cases tested. The system is moderately priced and has facilitated maintenance of radiodiagnostic interpretive services at a satellite office form the central hospital location.     

IL-1beta increases intracellular calcium through an IL-1 type 1 receptor mediated mechanism in C6 astrocytic cells.

Interleukin-1β (IL-1β) is a cytokine that regulates a variety of biological processes. In addition to its traditional role in the immune system, IL-1β plays an integral role in neural-immune and developmental processes in the nervous system. The pleiotropic ability of IL-1β may be due to the activation of different signal transduction mechanisms in specific cell types or under certain cellular conditions. We have previously demonstrated that IL-1β regulates healing and repair in the developing, mammalian nervous system. In the damaged perinatal mouse brain, IL-1β is expressed in astrocytes that change from a stellate to a spindle-shaped morphology. The spindle-shaped astrocytes enclose the wound, separating the healthy from damaged neural tissue. The shape change and subsequent repair processes are IL-1β activity-dependent, acting through the IL-1 type 1 receptor (IL-1R1), as co-application of the IL-1type 1 receptor antagonist protein (IL-1ra) blocks IL-1β induced effects. In the C6 astrocytic cell line, IL-1β induced similar shape changes and upregulated expression of the cytoskeletal protein, glial fibrillary acidic protein (GFAP). Since cytoskeletal changes, as well as specific signal transduction mechanisms, are associated with increases in intracellular calcium ([Ca²⁺]_i), studies were carried out to determine if increases in [Ca²⁺]_i induced by IL-1β occurred through activation of the IL-1R1 in C6 cells. Cells were treated with IL-1β and/or IL-1ra, followed by measurement of relative changes in [Ca²⁺]_i using fura-2 fluorescence imaging methods. IL-1β increased [Ca²⁺]_i levels in a dose and time dependent manner. Treatment with IL-1ra blocked IL-1β induced increases in [Ca²⁺]_i, indicating that IL-1β acts through the IL-1R1. Immunocytochemistry experiments showed that untreated C6 cells normally express IL-1β, IL-1ra, and IL-1R1. Thus, IL-1 system molecules may play a role in normal C6 astrocyte physiology.