Characterization of critical residues in the cytoplasmic domain of the human interleukin-5 receptor α chain required for growth signal transduction

Interleukin (IL)-5 binds to a cell surface receptor composed of two polypeptide chains, α and β, both belonging to the hemopoietic cytokine receptor family. Mouse cells expressing common mouse β chain (AIC2B) that were transfected with human IL-5 receptor (R)α cDNA proliferated in response to picomolar concentrations of human IL-5, indicating that a functional receptor was reconstituted. We show that in these cells, human (h)IL-5 as well as mouse (m)IL-3 induce tyrosine phosphorylation of β chain and JAK 2 kinase. Phosphorylated β receptor was co-precipitated with anti-JAK 2 antibodies, suggesting that both molecules were physically associated. IL-5 and IL-3 also induce cytosolic DNA binding activity as measured by an electrophoretic mobility shift assay using the interferon-γ responsive region of human Fc γ1 gene DNA element. A deletion mutant of hIL-5Rα lacking the cytoplasmic part could bind hIL-5 normally in association with the β chain, but was unable to transmit a biological signal. The cytoplasmic domain was also indispensable for tyrosine phosphorylation and activation of DNA binding proteins. A membrane-proximal proline-rich element of the hIL-5Rα cytoplasmic domain that is conserved among different members of the hemopoietic cytokine receptor family was essential for biological activity. Point mutations in this motif also knocked out IL-5-inducible JAK 2 phosphorylation.     

Psychopathology in children with epilepsy: a meta-analysis

OBJECTIVE: To examine the types and severity of psychopathology in children with epilepsy. METHODS: A series of meta-analyses were conducted to review 46 studies, including 2,434 children with epilepsy. RESULTS: Effect sizes were medium to large for comparisons with children from the general population, which indicates that children with epilepsy are at increased risk for psychopathology, including internalizing and externalizing behavior problems. Comparisons with children with another chronic illness revealed small to medium effect sizes, indicating that psychopathology in children with epilepsy may partly be attributed to chronicity of the disease. Attention problems, thought problems, and social problems proved to be relatively specific to epilepsy. Comparisons with siblings suggested that psychopathology in children with epilepsy may be associated with family factors, especially where behavioral disorders appear to be more generic. CONCLUSIONS: Clinicians should consider both neurological and psychosocial factors, including the family system, when treating psychopathology in children with epilepsy.     

Therapeutic and clinico-pathological factors in the survival of 1,469 patients with primary cutaneous malignant melanoma in clinical stage I

Summary Therapeutic and clinico-pathological data of 1,469 patients with clinical stage I malignant melanoma of the skin without histological evidence of fibrotic areas of regression were examined by multivariate regression analysis. In accordance with a previous analysis anatomical site of tumour, tumour thickness, level of invasion, mitotic rate, ulceration, lymphhocytic reaction, dominant type of invasive tumour cell, and sex were found to act as independent risk factors. The present analysis, furthermore, showed that size of resection margin, diagnostic biopsy, removal of the deep fascia, age at surgery, as well as presence and depth of nevus cells did not influence prognosis when adjusting for the independent risk factors.     

Extinction in fear conditioning: Effects on startle modulation and evaluative self-reports

A basic feature of human evaluative conditioning is that the reported acquired valence of a previously neutral conditioned stimulus (CS) that has been paired with a valenced unconditioned stimulus (US), is resistant to extinction. The present study investigated whether startle modulation, sometimes presented as an index of acquired valence, reflected this basic feature. In a differential fear conditioning paradigm ( n = 38) with an electrocutaneous stimulus as the US, a strong extinction manipulation was conducted by removing the US-electrodes and by extended extinction trials. At the end of extinction, the results corroborated previous findings of evaluative conditioning in that the reported valence for CS+ was still more negative than for CS−, despite disappearance of the differential skin conductance responses. However, startle modulation did not show resistance-to-extinction. Results were discussed in terms of recent conceptualizations of extinction.     

A comparison between house mouse lines selected for attack latency or nest-building: Evidence for a genetic basis of alternative behavioral strategies

House mouse lines bidirectionally selected for either nest-building behavior or attack latency were tested for both attack latency and nest-building behavior under identical conditions. Male mice selected for high nest-building behavior had shorter attack latencies, i.e., were more aggressive, than those selected for low nest-building behavior and their randomly bred control lines. Conversely, male wild house mice selected for short attack latency showed more nest-building behavior than those selected for long attack latency when tested at 110 days of age. These findings imply a common genetic basis for control of aggression and nesting and support earlier proposals as to how animals may exhibit fundamentally different responses to environmental challenges, either reacting actively to aversive situations (aggressive and high-nesting animals: active copers) or adopting a passive strategy (nonaggressive and low-nesting animals: passive copers).     

The Penn State Worry Questionnaire and the Worry Domains Questionnaire: structure,reliability and validity

In this study the psychometric properties of the PSWQ and the WDQ were investigated in a community sample. The PSWQ proved to be unidimensional although the results indicated that the negatively keyed items contributed less to the general factor. Internal reliability of the PSWQ was satisfactory. Confirmatory analysis of the WDQ indicated that some alternations with regard to the content of the different domains had to be made. Furthermore, an additional health worry domain was included in the scale. This resulted in a revised revision of the WDQ. Internal reliability of the WDQ‐R was satisfactory, as well as consistencies of the different domains, with the exception of the Work Incompetence domain. High to moderate correlations were found between the two worry scales and measures of trait anxiety, depression and obsessive compulsive behaviour. In studying the relative impact of these constructs on worry it was found that the predictors accounted for 62 and 61% of the variance in the PSWQ and the WDQ‐R respectively, providing further evidence for the separate construct of worry. Copyright © 1999 John Wiley & Sons, Ltd.