The effect of the introduction of the Amsterdam Trauma Workflow Concept on mortality and functional outcome of patients with severe traumatic brain injury.

The purpose of this study was to analyze the effect of the introduction of an all-in workflow concept that included direct computed tomography (CT) scanning in the trauma room on mortality and functional outcome of trauma patients with severe traumatic brain injury (TBI) admitted to a level-1 trauma center. To this end, a retrospective comparison was made of a 1-year cohort prior to the implementation of the all-in workflow concept (Pre-CT in trauma room cohort [Pre-TRCT]) and a 1-year cohort after the implementation (Post-TRCT). All severely injured TBI patients aged 16 years or older that were presented in our level-1 trauma center and that underwent a CT of the head were initially included.

Clustering of endocytic organelles in parental and drug-resistant myeloid leukaemia cell lines lacking centrosomally organised microtubule arrays.

Spatial organisation and trafficking of endocytic organelles in mammalian cells is tightly regulated and dependent on cytoskeletal networks. The dynamics of endocytic pathways is modified in a number of diseases, including cancer, and notably in multidrug resistant (MDR) cells that are refractory to the effects of several anti-cancer agents. These cells often upregulate expression of drug-efflux pumps but this may be synergistic with alternative resistance mechanisms including increased acidification of endocytic organelles that enhances vesicular sequestration of weak-base anti-cancer drugs such as daunorubicin away from their nuclear target.

Temperature-, concentration- and cholesterol-dependent translocation of L- and D-octa-arginine across the plasma and nuclear membrane of CD34+ leukaemia cells.

Delineating the mechanisms by which cell-penetrating peptides, such as HIV-Tat peptide, oligoarginines and penetratin, gain access to cells has recently received intense scrutiny. Heightened interest in these entities stems from their ability to enhance cellular delivery of associated macromolecules, such as genes and proteins, suggesting that they may have widespread applications as drug-delivery vectors. Proposed uptake mechanisms include energy-independent plasma membrane translocation and energy-dependent vesicular uptake and internalization through endocytic pathways.

Effects of Na+/H+ exchanger inhibitors on subcellular localisation of endocytic organelles and intracellular dynamics of protein transduction domains HIV-TAT peptide and octaarginine.

Protein transduction domains such as those derived from the HIV protein TAT have great potential as vectors for delivery of therapeutic entities such as genes and proteins into cells. Extensive studies have shown that a major fraction of the most studied variants enters cells via an endocytic mechanism. However, controversy surrounds the exact uptake mechanism and whether a specific pathway is utilised.

Intracellular traffic and fate of protein transduction domains HIV-1 TAT peptide and octaarginine. Implications for their utilization as drug delivery vectors.

Transduction domains such as those derived from the HIV-TAT protein are candidate vectors for intracellular delivery of therapeutic macromolecules such as DNA and proteins. The mechanism by which they enter cells is controversial, and very little spatial information regarding the downstream fate of these peptides from the plasma membrane is available. We studied endocytic traffic of fluorescent conjugates of HIV-TAT peptide and octaarginine in human hematopoietic cell lines K562 (CD34-) and KG1a (CD34+) and substantiated our findings in epithelia cells.