Despite recent identification of specific pattern recognition receptors (PRR) for distinct microbial structures, data indicating their relevance in human infectious diseases are limited. We determined the expression levels of the Toll-like receptor (TLR)2 and TLR4 by flow cytometry on granulocytes and monocytes of healthy neonates compared with healthy adults. The basal expression of TLR2 was only slightly lower in neonatal phagocytes, whereas no differences could be detected for TLR4. Analyzing neonates with sepsis, we found an impressive up-regulation of TLR2 on blood phagocytes already at initial presentation of symptoms. Comparison with C-reactive protein, IL-8, and IL-6 suggested that TLR2 expression on monocytes is comparably valuable as an early sepsis marker. Neonatal sepsis remains a leading cause of neonatal morbidity and mortality despite recent advances in neonatal intensive care (1,2). Although several deficiencies in the neonatal immune system have been revealed, including qualitative and quantitative deficits in phagocytes and humoral components (3-8), they may only partly explain the overwhelming nature of neonatal sepsis. The key for differences in the course of neonatal and adult sepsis might be molecular mechanisms involved in the initiation process of systemic inflammatory response syndromes, i.e. the activation of innate immune cells through invading microbes. In the innate immune system, many types of receptors participate in microbe detection. An exciting discovery was the finding that host organisms have developed a set of specific receptors (PRR) for the recognition of highly conserved and essential molecular structures of microbes [pathogen-associated molecular patterns, PAMP)] (9). TLR2 was identified as a receptor for Gram-positive peptidoglycan and bacterial lipopeptides (10,11), whereas TLR4 is part of a receptor complex recognizing Gram-negative bacterial LPS and is required for LPS signal transduction (12). Both finally trigger inflammatory responses through an IL-1 receptor-like pathway that uses an adapter protein (MyD88), IL-1 receptor associated kinase (IRAK), and tumor necrosis factor receptor-associated factor (TRAF)-6 signaling to activate nuclear factot (NF)B and mitogen-activated protein kinase dependent signaling pathways (13). They initiate distinct genetic programs, including the induction of a subset of chemokines like macrophage inflammatory protein (MIP)-1␣, MIP-1␤, and RANTES (regulated upon activation, normal t-cell expressed and secreted) mediated by TLR2 and TLR4, whereas IP-10 is preferentially induced by TLR4 and IL-8 preferentially by TLR2 (14). The model of microbial recognition has now evolved into one in which immune cells use multiple PRR to detect several features of a microbe simultaneously. The signal pattern transduced by the combination of different innate immune receptors may be the key to the kind of immune response that is elicited (15).Except for in vitro experiments or murine models, data regarding the expression and in vivo relevance of TLR in ...

No abstract

Since 1971, when W.P. Faulk and G.M. Taylor published "An immunocolloid method for the electron microscope", colloidal gold has become a very widely used marker in microscopy. It has been used to detect a huge range of cellular and extracellular constituents by in situ hybridization, immunogold, lectin-gold, and enzyme-gold labeling. Besides its use in light microscopic immunogold and lectin-gold silver staining, colloidal gold remains the label of choice for transmission electron microscopy studying thin sections, freeze-etch, and surface replicas, as well as for scanning electron microscopy. The year 1996 is the 25th anniversary of the introduction of colloidal gold as a marker in immunoelectron microscopy and this overview outlines some of the major milestones in the development of the colloidal gold marker system.

No abstract

School can be regarded as an important factor in the development of children's values and attitudes. Given this great importance of justice experiences for students' development, this study aimed at examining the influence of perceived injustice in school on students' emotions, well-being, and behavior with an experimental longitudinal design. In total, 196 students participated in this study and came to the university with their classes to receive extra teaching once a week for six consecutive weeks. To manipulate justice perceptions, a scenario of arbitrary privilege was chosen to lead students of the experimental group to experience injustice from a beneficiary perspective. We found that students in the experimental group reported higher well-being and a higher appreciation of the opportunity to learn than the control group did. Additionally, they showed an increase in justicerelated negative emotions over time; that is, they expressed more of a bad conscience and stronger feelings of anger the more they became aware of their privilege. This study shows that even subtle experiences of injustice in school can have an impact on students' outcomes. These results are discussed with regard to practical implications.