Seroprevalence of hepatitis E virus (HEV) in humans living in high pig density areas of Germany

An increase in acute autochthonous hepatitis E virus (HEV) infections has been recorded in Germany. These are suspected to be zoonotically transmitted from wild boar, deer and domestic pig. The latter may represent a major reservoir for HEV. In this study, 537 sera from humans living in Westphalia and Lower Saxony, representing areas of high pig density in Germany, were tested for the presence of HEV-specific antibodies. Among them were 302 individuals with occupational, direct contact to pigs and 235 individuals without direct contact to pigs. Two commercial tests and one in-house assay were applied for the detection of HEV-specific immunoglobulin G (IgG) antibodies. Sera were also tested in an assay that detects all classes of HEV-specific antibodies. Depending on the test used, the seroprevalence ranged from 4.1 to 27.9 %. Exposition to pigs was found to be associated with a significantly higher seroprevalence in subjects with contact to pigs (13.2–32.8 %) compared with that in non-exposed humans (7.7–21.7 %). In particular, individuals younger than 40 years with occupational exposure exhibited a markedly higher HEV seroprevalence compared with non-exposed individuals of that age group. In general, HEV seroprevalence increased with age resulting in a similar prevalence level in the age group of ≥50 years for exposed and non-exposed individuals. Analysis of all sera by a commercial anti-HEV IgM ELISA revealed 35 positive and 25 borderline samples. However, only one positive serum could be confirmed by an IgM line assay. Selected samples from IgM and/or IgG as well as total HEV antibody-positive individuals were also tested for the presence of HEV RNA. In one of the 78 samples, the only IgM ELISA positive and IgM line assay confirmed sample, RNA of HEV genotype 3 was detected. This sequence has high similarity to HEV sequences obtained from wild boars and domestic pigs from Germany and The Netherlands. This study demonstrates that in addition to the consumption of raw or undercooked meat, direct contact to pigs has to be considered as an additional risk factor for HEV infection.     

Loss of CD34 and high IGF2 are associated with malignant transformation in solitary fibrous tumors

The aim of this study was to characterize the subgroups of solitary fibrous tumor (SFT) and to investigate the expression of different biomarkers including CD34 and IGF2 in malignant transformation.     

β1-integrins dominate cell traffic of leukemic cells in human bone-marrow stroma

Migration patterns of leukemic cells in bone marrow are largely regulated by cell contacts between leukemic cells and stromal cells or extra-cellular matrix. The mechanism of this interaction with bone-marrow stromal cells was studied in a human in vitro model. Migration behavior of erythroleukemia cell line K562, derived from a patient with chronic myeloid leukemia, was compared with that of the erythroleukemia cell line HEL92.1.7 and the promyelocytic leukemia cell line HL60 from acute leukemias. Interaction varied between low binding affinity (K562) to intensive cell interaction (HEL92.1.7) followed by invasion into the stromal cell monolayer. Some of the HL60 cells adhered to stromal cells, while the remainder migrated into the stromal cell monolayer. The role of adhesion molecules in these cell interactions was determined. Distinct expression of β₁-integrins ICAM-I, CD44 and VCAM-I was detected on the different cell lines. Inhibition studies pointed to a dominant role of VLA-4- and VLA-5-mediated interactions. K562 lacked VLA-4 and a low affinity of the VLA-5 on these cells resulted in an absence of binding to the bone-marrow stroma. These results indicate the VLA-5/fibronectin, VLA-4/fibronectin and the VLA-4/VCAM-I interaction pathways between leukemic cells and bone-marrow stroma. © 1996 Wiley-Liss, Inc.     

In vitro exposure of isolated cells to native gaseous compounds Development and validation of an optimized system for human lung cells

An exposure system for adherent growing cells to native gaseous compounds was developed using air/liquid culture techniques on the basis of the Cultex system'. In contrast to other exposure systems the reproducible testing of native environmentally relevant gases without changing their physical or chemical properties including heating, CO2- content and humidity is possible. Specially designed systems for medium flow and gas support guarantee the nutrification and humidification as well as the direct gas contact of the exposed cells which are cultivated on microporous membranes (0.4 microm pore size). The system works independently of a cell culture incubator offering the possibility to analyze any relevant gas mixture directly under indoor or outdoor conditions. Several experimental approaches were carried out to characterize the properties of the system. In exploratory experiments without cells, the reproducibility and quality of the gas/membrane contact could be demonstrated. Exposures of human lung fibroblasts (Lk004 cells) and human lung epithelial cells (HFBE-21 cells) to synthetic air, ozone (202 ppb, 510 ppb) and nitrogen dioxide (75 ppb to 1,200 ppb) established that cells could be treated for 120 minutes without significant loss of cellular viability. At the same time, the experiments confirmed that such exposure times are long enough to detect biological effects of environmentally relevant gas mixtures. The analysis of viability (viable cell number, tetrazoliumsalt cleavage) and intracellular end-points (oxidized/reduced glutathione, ATP/ADP) showed that both gases induced relevant cellular changes. In summary, the efficiency and practicability of this newly developed exposure system for adherent human lung cells could be clearly demonstrated.