AIDS, Kaposi sarcoma, and the lymphatic system: update and reflections

Based on ongoing basic and clinical investigations, further evidence is presented that the AIDS-Kaposi sarcoma (AIDS-KS) complex involves a progressive disturbance of the blood-lymph circulatory loop of fluid, macromolecules, and migrating cells. We first surveyed the spectrum of vascular abnormalities including Kaposi sarcoma (KS) found in the AIDS/ARC population, then non-invasively imaged lymphatic system abnormalities in AIDS-KS by whole body lymphangioscintigraphy, and finally examined the biologic behavior of AIDS-KS cells in long-term tissue culture. These observations are viewed in terms of the lymphatic and blood vascular route of entry and transport of free and cell-associated virus and other opportunistic pathogens as well as poorly understood host endothelial-immune system interactions.     

Method to quantify accuracy of position feedback signals of a three-dimensional two-photon laser-scanning microscope

Two-photon laser-scanning microscopy enables to record neuronal network activity in three-dimensional space while maintaining single-cellular resolution. One of the proposed approaches combines galvanometric x-y scanning with piezo-driven objective movements and employs hardware feedback signals for position monitoring. However, readily applicable methods to quantify the accuracy of those feedback signals are currently lacking. Here we provide techniques based on contact-free laser reflection and laser triangulation for the quantification of positioning accuracy of each spatial axis. We found that the lateral feedback signals are sufficiently accurate (defined as <2.5 µm) for a wide range of scan trajectories and frequencies. We further show that axial positioning accuracy does not only depend on objective acceleration and mass but also its geometry. We conclude that the introduced methods allow a reliable quantification of position feedback signals in a cost-efficient, easy-to-install manner and should be applicable for a wide range of two-photon laser scanning microscopes.OCIS codes: (180.6900) Three-dimensional microscopy, (180.4315) Nonlinear microscopy, (170.0180) Microscopy, (170.2520) Fluorescence microscopy, (180.2520) Fluorescence microscopy     

Association studies of novel obesity-related gene variants with quantitative metabolic phenotypes in a population-based sample of 6,039 Danish individuals

Aims/hypothesis  

Genome-wide association studies have identified novel WHR and BMI susceptibility loci. The aim of this study was to elucidate if any of these loci had an effect on quantitative measures of glucose homeostasis, including estimates of insulin release and insulin sensitivity in an epidemiological setting.     

Cancer occurrence in Danish diabetic patients: duration and insulin effects

Aims/hypothesis  

Cancer is more frequent among diabetes patients, but it is unknown how this excess varies with duration of diabetes and insulin use. The aim of this study was to analyse disease data to examine this issue further.     

Preparation of unnatural N-to-N and C-to-C protein fusions

Standard genetic approaches allow the production of protein composites by fusion of polypeptides in head-to-tail fashion. Some applications would benefit from constructions that are genetically impossible, such as the site-specific linkage of proteins via their N or C termini, when a remaining free terminus is required for biological activity. We developed a method for the production of N-to-N and C-to-C dimers, with full retention of the biological activity of both fusion partners and without inflicting chemical damage on the proteins to be joined. We use sortase A to install on the N or C terminus of proteins of interest the requisite modifications to execute a strain-promoted copper-free cycloaddition and show that the ensuing ligation proceeds efficiently. Applied here to protein-protein fusions, the method reported can be extended to connecting proteins with any entity of interest.     

The EBMT activity survey: 1990-2010

A total of 654 centers from 48 countries were contacted for the 2010 survey. In all, 634 centers reported a total of 33?362 hematopoietic SCT (HSCT) with 30?012 patients receiving their first transplant (12?276 allogeneic (41%) and 17?736 autologous (59%)). Main indications were leukemias: 9355 (31%; 93% allogeneic), lymphoid neoplasias specifically Non Hodgkin's lymphoma, Hodgkin's lymphoma and plasma cell disorders: 17?362 (58%; 12% allogeneic), solid tumors: 1585 (5%; 6% allogeneic) and non-malignant disorders: 1609 (6%; 88% allogeneic). There were more unrelated donors than HLA-identical sibling donors (53% versus 41%); the proportion of peripheral blood as stem cell source was 99% for autologous and 71% for allogeneic HSCT. Cord blood was primarily used in allogeneic transplants (6% of total) with three autologous cord blood HSCT being reported. The number of transplants has increased by 19% since 2005 (allogeneic 37% and autologous 9%) and continued to increase by about 1100 HSCT per year since 2000. Patterns of increase were distinct and different. The data show the development of transplantation in Europe since 1990, with the number of patients receiving a HSCT increasing from 4200 to over 30?000 annually. The most impressive trend seen is the steady increase of unrelated donor transplantation, in parallel to the availability of unrelated donors through donor registries.