Smoking and psychiatric disorders: Have subthreshold disorders been overlooked?

INTRODUCTION: The association between smoking and mental disorders has been confirmed by several studies using cross-sectional and retrospective designs. The present study illustrates the need for differentiating subthreshold psychiatric disorders in the analysis. METHODS: The analysis is based on cumulative ("lifetime") prevalences of mental disorders and smoking in the Zurich study. This is a longitudinal community study with a stratified sample of 591 participants and six interviews from 1979 to 1999. RESULTS: The percentage of lifetime smokers in the Zurich study was higher both in persons with a lifetime psychiatric diagnosis (72%) and in persons with subthreshold disorders (60%) than in those without any diagnosis (40%). DISCUSSION: The association between smoking and mental disorders turned out to be clearly stronger if subthreshold mental disorders were appropriately considered in the analyses. Constructing appropriate reference groups is as crucial for the analysis of mental disorders and their outcomes as constructing adequate diagnostic groups

Synthesis and Organization of Hyaluronan and Versican by Embryonic Stem Cells Undergoing Embryoid Body Differentiation

Embryonic stem cells (ESCs) provide a convenient model to probe the molecular and cellular dynamics of developmental cell morphogenesis. ESC differentiation in vitro via embryoid bodies (EBs) recapitulates many aspects of early stages of development, including the epithelial–mesenchymal transition (EMT) of pluripotent cells into more differentiated progeny. Hyaluronan and versican are important extracellular mediators of EMT processes, yet the temporal expression and spatial distribution of these extracellular matrix (ECM) molecules during EB differentiation remains undefined. Thus, the objective of this study was to evaluate the synthesis and organization of hyaluronan and versican by using murine ESCs during EB differentiation. Hyaluronan and versican (V0 and V1 isoforms), visualized by immunohistochemistry and evaluated biochemically, accumulated within EBs during the course of differentiation. Interestingly, increasing amounts of a 70-kDa proteolytic fragment of versican were also detected over time, along with ADAMTS-1 and -5 protein expression. ESCs expressed each of the hyaluronan synthases (HAS) -1, -2, and -3 and versican splice variants (V0, V1, V2, and V3) throughout EB differentiation, but HAS-2, V0, and V1 were expressed at significantly increased levels at each time point examined. Hyaluronan and versican exhibited overlapping expression patterns within EBs in regions of low cell density, and versican expression was excluded from clusters of epithelial (cytokeratin-positive) cells but was enriched within the vicinity of mesenchymal (N-cadherin-positive) cells. These results indicate that hyaluronan and versican synthesized by ESCs within EB microenvironments are associated with EMT processes and furthermore suggest that endogenously produced ECM molecules play a role in ESC differentiation. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. (J Histochem Cytochem 58:345–358, 2010