Role of IL-6 and the soluble IL-6 receptor in inhibition of VCAM-1 gene expression

Adhesion molecules such as VCAM-1 and ICAM-1 are increased in the central nervous system (CNS) during inflammatory responses and contribute to extravasation of leukocytes across the blood-brain barrier (BBB) and into CNS parenchyma. Astrocytes contribute to the structural integrity of the BBB and can be induced to express VCAM-1 and ICAM-1 in response to cytokines such as TNF-alpha, IL-1beta, and IFN-gamma. In this study, we investigated the influence of IL-6 on astroglial adhesion molecule expression. IL-6, the soluble form of the IL-6R (sIL-6R), or both IL-6 plus sIL-6R, had no effect on VCAM-1 or ICAM-1 gene expression. Interestingly, the IL-6/sIL-6R complex inhibited TNF-alpha-induced VCAM-1 gene expression but did not affect TNF-alpha-induced ICAM-1 expression. The inhibitory effect of IL-6/sIL-6R complex was reversed by the inclusion of anti-IL-6R and gp130 Abs, demonstrating the specificity of the response. A highly active fusion protein of sIL-6R and IL-6, covalently linked by a flexible peptide, which is designated H-IL-6, also inhibited TNF-alpha-induced VCAM-1 expression. sIL-6R alone was an effective inhibitor of TNF-alpha-induced VCAM-1 due to endogenous IL-6 production. These results indicate that the IL-6 system has an unexpected negative effect on adhesion molecule expression in glial cells and may function as an immunosuppressive cytokine within the CNS.     

Multiple central giant cell lesions with a Noonan-like phenotype

A small number of patients with the phenotypic features of Noonan syndrome have also developed giant cell lesions of the jaws similar to those seen in cherubism. This case report describes an individual with the features of the recently described Noonan-like/multiple giant cell lesion syndrome. Previously reported cases and issues relative to diagnosis and management are considered.     

The substrates of a sodium- and chloride-coupled gamma-aminobutyric acid transporter protect multiple sites throughout the protein against proteolytic cleavage

Fragments of the (Na(+) + Cl-)-coupled GABAA transporter were produced by proteolysis of membrane vesicles and reconstituted preparations from rat brain. The former were digested with Pronase, the latter with trypsin. Fragments with different apparent molecular masses were recognized by sequence-directed antibodies raised against this transporter. When GABA was present in the digestion medium, the generation of these fragments was almost entirely blocked. At the same time, the neurotransmitter largely prevented the loss of activity caused by the protease. The effect was specific for GABA; protection was not afforded by other neurotransmitters. It was only observed when the two cosubstrates, sodium and chloride, were present on the same side of the membrane as GABA. The results indicate that the transporter may exist in two conformations. In the absence of one or more of the substrates, multiple sites located throughout the transporter are accessible to the proteases. In the presence of all three substrates--conditions favoring the formation of the translocation complex--the conformation is changed such that these sites become inaccessible to protease action.     

Experimental comparison of fourier transformation and model-fitting methods of spectral analysis

A summary of the results of an extensive comparative experimental study of Fourier transformation and model-fitting methods of spectral analysis of random time-series data is presented. It is illustrated that Fourier transformation methods can be an essential companion to model-fitting methods even for short data segments with underlying sharp spectral peaks. The best spectrum estimates can be obtained by taking advantage of the strengths of both types of methods. For example, it is shown that detection and estimation of the frequencies of spectral lines for short data segments can be best accomplished using certain parametric methods in conjunction with Fourier transformation methods to aid in model-order selection and identification of spurious peaks in the parametric spectrum estimate, and that estimation of amplitude and phase for sine-wave removal, given frequency estimates, and spectrum estimation after sine-wave removal can often be best accomplished with Fourier transformation methods alone.     

Organizational socialization: Its content and consequences.

Content dimensions of the socialization domain were defined to determine relationships between learning particular features of a job/organization and the process and outcomes of socialization. Six socialization dimensions (performance proficiency, politics, language, people, organizational goals/values, and history) were supported by a factor analysis on data from 594 full-time professionals. The socialization process was then examined by comparing 3 groups of respondents who did not change jobs, changed jobs within the organization, or changed jobs and organizations. Results showed these groups had significantly different response patterns on all dimensions. Finally, relationships between socialization content and career outcomes showed the dimensions accounted for more variance in all criteria than typical tenure operationalizations of socialization. Furthermore, socialization changes were significantly related to changes in career outcomes for 1-, 2-, and 3-yr time intervals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)