Information processing, social cognition, and psychiatric rehabilitation in schizophrenia

Pattern electroretinograms are small physiologic signals that require good patient cooperation and long recording times, particularly when conditions are not optimal. Six electrodes were compared to evaluate their efficacy. Pattern electroretinograms were recorded in eight healthy volunteers to high-contrast, pattern-reversal checks (40' width) with Burian-Allen, DTL fiber, C-glide, gold foil, HK loop and skin electrodes. Raw data for 320 reversals were analyzed off-line to evaluate signal amplitude, quality, P50 and N95 peak times, artifact rate and electrical noise. Insertion time, impedance and subjective comfort were also assessed. The Burian-Allen contact lens electrode gave the largest signal and lowest impedance but was the least comfortable and had the highest artifact rate (p < 0.01). A skin electrode on the lower eyelid produced the smallest pattern electroretinogram with the poorest quality (p < 0.05). The four other electrodes were foil or fiber electrodes in contact with the tear film, conjunctiva and/or the inferior cornea. The signal from these showed only minor differences. When electrodes are compared for pattern electroretinograms recording, the foil and fiber electrodes do not differ substantially but contact lens and skin electrodes show substantial disadvantages.     

The binding of receptor-recognized alpha2-macroglobulin to the low density lipoprotein receptor-related protein and the alpha2M signaling receptor is decoupled by oxidation

Receptor-recognized forms of alpha2-macroglobulin (alpha2M*) bind to two classes of cellular receptors, a high affinity site comprising approximately 1500 sites/cell and a lower affinity site comprising about 60,000 sites/cell. The latter class has been identified as the so-called low density lipoprotein receptor-related protein (LRP). Ligation of receptors distinct from LRP activates cell signaling pathways. Strong circumstantial evidence suggests that the high affinity binding sites are responsible for cell signaling induced by alpha2M*. Using sodium hypochlorite, a powerful oxidant produced by the H2O2-myeloperoxidase-Cl- system, we now demonstrate that binding to the high affinity sites correlates directly with activation of the signaling cascade. Oxidation of alpha2M* using 200 microM hypochlorite completely abolishes its binding to LRP without affecting its ability to activate the macrophage signaling cascade. Scatchard analysis shows binding to a single class of high affinity sites (Kd - 71 +/- 12 pM). Surprisingly, oxidation of native alpha2-macroglobulin (alpha2M) with 125 microM hypochlorite results in the exposure of its receptor-binding site to LRP, but the ligand is unable to induce cell signaling. Scatchard analysis shows binding to a single class of lower affinity sites (Kd - 0.7 +/- 0.15 nM). Oxidation of a cloned and expressed carboxyl-terminal 20-kDa fragment of alpha2M (RBF), which is capable of binding to both LRP and the signaling receptor, results in no significant change in its binding Kd, supporting our earlier finding that the oxidation-sensitive site is predominantly outside of RBF. Attempts to understand the mechanism responsible for the selective exposure of LRP-binding sites in oxidized native alpha2M suggest that partial protein unfolding may be the most likely mechanism. These studies provide strong evidence that the high affinity sites (Kd - 71 pM) are the alpha2M* signaling receptor.