Although evidence indicates that NIV can be used as the treatment of first choice for several indications, it is still underutilized in the acute setting. These guidelines provide evidence-based information about the indications for, and limitations of, NIV in the treatment of ARF.

ERM (Ezrin/Radixin/Moesin) proteins are crosslinkers between plasma membrane proteins and the actin cytoskeleton, thereby involved in the formation of cell adhesion sites. Earlier work showed that Ezrin links syndecan-2 to the actin cytoskeleton. Here we provide evidence that the Ezrin N-terminal domain binds to the syndecan-2 cytoplasmic domain with an estimated K D of 0.71 W WM and without the requirement of other proteins. We also studied the regions in the syndecan-2 cytoplasmic domain implicated in the binding to Ezrin. By truncating the syndecan-2 cytoplasmic domain and by oligopeptide competition assays we show that the Ezrin-binding sequence is not located in the positively charged juxtamembrane region (RMRKK), but in the neighboring sequence DEGSYD. We therefore conclude that the consensus sequence for Ezrin binding is unique among membrane proteins, suggesting a distinct regulation. ß

No abstract

Syndecans are cell-surface heparan sulfate proteoglycans, which perform a variety of functions in the cell. Most important, they are co-receptors for growth factors and mediate cell-cell and cell-matrix interactions. Four syndecans (syndecan 1-4) have been described in different species. The aim of this work was the cloning and characterization of human syndecan-3. The human syndecan-3 sequence has high homology to the rat and mouse sequences, with the exception of the 5'-region. Syndecan-3 mRNA is mostly expressed in the nervous system, the adrenal gland, and the spleen. When different cell lines were transiently transfected with full-length syndecan-3 cDNA, it was localized to the membrane and induced the formation of long filopodia-like structures, microspikes, and varicosities. Consequently, the actin cytoskeleton was re-organized, since actin staining was mostly found in the cellular extensions and at the cell periphery, co-localizing with the syndecan-3 staining. The development of the phenotype depended on the presence of sugar chains, as transfected glycosaminoglycan-deficient Chinese hamster ovary (CHO) 745 cells did not show these structural changes, nor did transfected CHO K1 cells in the presence of heparin. The similarity of the cloned DNA sequence with that of other mammalian species and the high expression in the nervous system led us to the assumption that human syndecan-3 could perform comparable functions to those described for syndecan-3 in rat and mouse. Additionally, transient transfection experiments suggest a role of human syndecan-3 in the organization of cell shape by affecting the actin cytoskeleton, possibly by transferring signals from the cell surface in a sugar-dependent mechanism.

Syndecans, transmembrane heparan sulfate proteoglycans (HSPG), mediate cell-cell and cell-matrix adhesion thereby controlling cell movement and shape. Syndecan cytoplasmic domains are very short (ca. 30 amino acids) and divided into two constant regions (C1 and C2) separated by one variable (V) region. Here we attempted to map the cytoplasmic region responsible for the filopodia-inducing effect of syndecan-3. We found that only the C1-region was necessary for this effect. In addition, the deletion of the C2-region led to extensive membrane blebbing. Nevertheless, the elimination of the entire cytoplasmic region did not affect delivery of syndecan-3 to the plasma membrane. These results indicate that the different regions of syndecan-3 cytoplasmic domain have different functions probably by binding to distinct proteins.

No abstract

Non-invasive ventilation is still not as widely implemented in clinical medicine as would be expected on the basis of the scientific literature. The aim of the present guidelines is to further propagate NIV for the treatment of ARI.

Weaning was successful in two thirds of patients who had been on prolonged mechanical ventilation and had then been transferred to weaning facilities staffed by chest physicians. These centres effectively improved the quality of care of patients on prolonged mechanical ventilation by avoiding long-term invasive ventilation and sparing cost-intensive ICU resources. The problems that still exist may be overcome by a network of weaning facilities.