Lymphocyte trafficking plays a critical role in disseminating specifically primed lymphocytes all over the body. Most concepts on the interaction of adhesion molecules on lymphocyte subsets and specialized endothelia such as those in high endothelial venules (HEV) are based on animal experiments as kinetic studies cannot be performed in humans. We therefore characterized lymphocyte subsets in the wall of HEV and in the lumen of lymphatics of 18 human palatine tonsils by immunohistology. All subsets studied were found in the wall of HEV (% of lymphocytes): 32% CD20+, 50% CD3+, 14% CD4+, 32% CD8+ and also 21% CD45RA+ and 39% CD45RO+. In the lymphatics, used to indicate lymphocytes emigrating from the tonsils, a different composition was found; e.g. many more T cells and three times more CD45RA+ than RO+ lymphocytes. Thus, HEV are not a selective entry site nor lymphatics an exit for specific lymphocyte subsets only, at least in these tonsils with chronic stimulation.
Genomics-driven discovery of microbial species have provided extraordinary insights into the biodiversity of human microbiota. High resolution genomics to investigate species- and strain-level diversity and mechanistic studies, however, rely on the availability of individual microbes from a complex microbial consortia. Here, we describe and validate a streamlined workflow for cultivating microbes from the skin, oral, and gut microbiota, informed by metagenomic sequencing, mass spectrometry, and strain profiling.
Contrast enhanced MR-angiography of the hand arteries in the described technique is a promising method. Compared to intraarterial digital subtraction angiography (IA-DSA) MRA still has limitations concerning spatial and temporal resolution. For clinical evaluation comparative studies with IA-DSA are necessary.
General anesthetic drugs were introduced more than 160 years ago and are indispensable in daily surgery at hospitals. Interestingly, their mode of action remains largely unresolved. At present, there are two schools, one favoring specific (direct) interactions of the drugs with proteins of the central nervous system and a second adhering to nonspecific mechanisms through a modulation of biophysical membrane properties. We have focused on the latter mechanism and studied the effects of R-(−), S-(+)-ketamine and propofol on the biophysical properties of lipid model membranes composed of palmitoyl oleoyl phosphatidylcholine by a combination of X-ray diffraction and all-atom molecular dynamics simulations. In agreement with several previous studies, we do not find significant changes to the overall membrane structure up to 8 mol % drug content. However, we observed that the insertion of drugs within the lipid/water interface caused significant changes of lateral pressures within the membrane [1]. The changes are predicted to be stereospecific and large enough to affect the opening probability of ion channels at concentrations that compare remarkably well to clinically applied concentrations. Our results thus provide a novel basis for rational anesthetic drug design. [1] Jerabek H, Pabst G, Rappolt M, Stockner T. Membrane-mediated effect on ion channels induced by the anesthetic drug ketamine.
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