Clostridium difficile toxins influence hepatocyte protein synthesis through the interleukin 1 receptor.

HYPOTHESIS: Clostridium difficile toxins require interleukin 1 (IL-1) production or a functioning IL-1 receptor to elicit acute-phase protein production by murine hepatocytes. DESIGN: Experimental study. SETTING: Research laboratory at the DVA Medical Center, St Louis, Mo. CELLS STUDIED: Hepatocytes prepared from normal mice, from knockout mice deficient in IL-1 production due to loss of IL-1 converting enzyme, or from knockout mice deficient in the IL-1 p80 receptor. INTERVENTIONS: Cells were treated with lipopolysaccharide, a crude C difficile toxin extract, or purified C difficile toxins A or B for 24 hours in vitro, then radiolabeled with (35)S methionine. Newly synthesized acute-phase proteins were identified by electrophoresis and autoradiography. MAIN OUTCOME MEASURES: Synthesis of a 23-kd acute-phase protein in response to the various stimuli. RESULTS: Lipopolysaccharide, C difficile culture extract, and purified toxins A and B stimulated the synthesis of the 23-kd acute-phase protein by hepatocytes from normal mice and by hepatocytes from knockout mice deficient in the IL-1 converting enzyme. However, hepatocytes from knockout mice deficient in the IL-1 p80 receptor failed to produce this acute-phase protein when treated with the C difficile toxins, although they responded fully to lipopolysaccharide. CONCLUSIONS: Stimulation of acute-phase protein synthesis by C difficile toxins does not require IL-1 production, but does require a functioning IL-1 p80 receptor. This suggests that some of the actions of these toxins are mediated by this receptor.

How much do 'attention' tests tell us?

Twelve measures commonly used to assess attentional processes were examined in a sample of 120 outpatients referred for neuropsychological evaluation. A single factor solution emerged. A second analysis partially replicated factors derived by Shum. McFarland, Bain, and Humphreys (1990). Classification rates (impaired vs. unimpaired) for the measures are presented. The implications of these findings for clinical assessment of attention are discussed

On the relationship of the five-factor personality model to personality disorders: four reservations.

McCrae and Costa since 1986 have proferred a five-factor personality model as a lingua franca among different psychometric test users, and they suggest that their operationalization of the five-factor model, the NEO Personality Inventory, may also be useful in the clinical assessment of the abnormal personality. The present study examined the inventory and its relationship to the 11 personality disorders of Axis II of DSM-III-R in a sample of 180 adults. Correlational multivariate analyses appear to indicate a limited usefulness of the five-factor model in the understanding of personality disorders, and four major objections are offered. Further research with clinical samples, other models of personality, and other measures of personality disorders are encouraged.

Psychometric properties of a hurricane coping self-efficacy measure.

This brief report describes the psychometric properties of an instrument designed to measure Hurricane Coping Self-Efficacy (HCSE). Survivors of Hurricane Andrew (n = 165) and Hurricane Opal (n = 63) completed the HCSE and assessments of optimism, social support, distress, and resource loss. Principal components factor analyses revealed a unidimensional structure for the HCSE. Internal consistency of the HCSE was strong. In both samples, HCSE was positively associated with optimism and social support, but negatively associated with general psychological distress, trauma related distress, and resource loss. Finally, hierarchical regression analyses demonstrated that the HCSE explained a significant amount of experimental variance for intrusive thoughts and avoidance after controlling for social support, lost resources, and optimism.

A comparison of computerized and standard versions of the Wisconsin Card Sorting Test.

The manual version of the Wisconsin Card Sorting Test (WCST) is the most frequently used neuropsychological instrument for differentiating normal from populations with frontal-lobe impairments. A number of computerized versions have become available, and their ability to accurately detect frontal-lobe dysfunction is based on the assumption of equivalence with the standard manual version. Accordingly, comparisons of the distribution properties of central tendency, variability, and shape between the manual version with four computerized versions of the WCST were performed (n = 22 per condition). None of the computerized versions were found to be equivalent to the manual version on all assessment measures. Given the discrepancies between the manual and computerized versions, it is concluded that the norms provided for the standard manual presentation method should not be used for the computerized versions, and for continued use of the computerized versions, new norms for computer versions need to be established. Thus, clinicians and experimenters must use caution when basing conclusions on scores from computer versions of the WCST.

Clostridium difficile toxin: cytoskeletal changes and lactate dehydrogenase release in hepatocytes.

BACKGROUND: We have found that Clostridium difficile toxins can evoke hepatocyte acute-phase protein synthesis, and that this effect is dependent on a functioning interleukin-1 (IL-1) receptor. The present study was undertaken to determine if C. difficile toxicity, as determined by actin rearrangement and lactate dehydrogenase (LDH) release, also requires a functioning IL-1 receptor. METHODS: Primary hepatocyte cultures were prepared from normal mice, knockout mice deficient in the IL-1-converting enzyme (ICE), and knockout mice deficient in the IL-1 p80 receptor. Hepatocytes were treated for 24 h with C. difficile culture extract, purified C. difficile toxin A, or purified C. difficile toxin B. The actin cytoskeleton was examined using confocal microscopy, and LDH release was measured by spectrophotometric analysis. RESULTS: C. difficile culture extract, toxin A, and toxin B induced collapse of the actin cytoskeleton in hepatocytes from normal mice. Hepatocytes from both the ICE-deficient mice and the IL-1 p80 receptor-deficient mice demonstrated similar responses to both toxins. These toxins also induced significant LDH release in a concentration-dependent fashion in the normal hepatocytes and the ICE-deficient hepatocytes. However, no significant increase in LDH release was observed in hepatocytes from IL-1 p80 receptor-deficient mice. CONCLUSIONS: C. difficile toxins induce actin cytoskeletal collapse independent of IL-1 or the IL-1 receptor. In contrast, toxin-stimulated LDH release was dependent on the presence of the IL-1 receptor. Thus, separate pathways appear to mediate toxic effects as manifested by actin rearrangement and LDH release.