Flotillin-1 (Reggie-2) contributes to Chlamydia pneumoniae growth and is associated with bacterial inclusion

Chlamydiae are obligate intracellular pathogens replicating only inside the eukaryotic host. Here, we studied the effect of human flotillin-1 protein on Chlamydia pneumoniae growth in human line (HL) and A549 epithelial cell lines. RNA interference was applied to disrupt flotillin-1-mediated endocytosis. Host-associated bacteria were detected by quantitative PCR, and C. pneumoniae growth was evaluated by inclusion counts. C. pneumoniae attachment to host cells was unaffected, but bacterial intracellular growth was attenuated in the flotillin-1-silenced cells. By using confocal microscopy, we detected flotillin-1 colocalized with the inclusion membrane protein A (IncA) in the C. pneumoniae inclusion membranes. In addition, flotillin-1 was associated with IncA in detergent-resistant membrane microdomains (DRMs) in biochemical fractioning. These results suggest that flotillin-1 localizes to the C. pneumoniae inclusion membrane and plays an important role for intracellular growth of C. pneumoniae.     

Exposure to flame retardants in electronics recycling sites

Waste electrical and electronic equipment (WEEE) contains various hazardous substances such as flame retardants (FRs). Inhalation exposures to many FRs simultaneously among WEEE recycling site workers have been little studied previously. The breathing zone airborne concentrations of five brominated FR compounds tetrabromobisphenol-A (TBBP-A), decabromodiphenylethane (DBDPE), hexabromocyclododecane, 1,2-bis(2,4,6-tribromophenoxy)ethane, hexabromobenzene, and one chlorinated FR (Dechlorane Plus?) were measured at four electronics recycling sites in two consecutive years. In addition, concentrations of polybrominated diphenyl ethers (PBDEs) and polybrominated biphenyls were measured. The three most abundant FRs in personal air samples were PBDEs (comprising mostly of deca-BDE), TBBP-A, and DBDPE, with mean concentrations ranging from 21 to 2320 ng m(-)(3), from 8.7 to 430 ng m(-3), and from 3.5 to 360 ng m(-3), respectively. At two of the sites, the emission control actions (such as improvements in ventilation and its maintenance and changes in cleaning habits) proved successful, the mean levels of FRs in personal samples being 10-68 and 14-79% of those from the previous year or alternatively below the limit of quantification. At the two remaining sites, the reductions in FR exposures were less consistent. The concentrations reported may pose a health hazard to the workers, although evaluation of the association between FR exposure and adverse health effects is hampered by lacking occupational exposure limits. Therefore, the exposures should be minimized by adequate control measures and maintaining good occupational hygiene practice.     

Results of the three rounds of the Finnish Prostate Cancer Screening Trial—The incidence of advanced cancer is decreased by screening

Screening for prostate cancer (PC) remains a controversial issue despite some new evidence on the mortality benefits of PC screening. We conducted a prospective, randomized screening trial in Finland to investigate whether screening decreases PC incidence. Here, we report the incidence results from three screening rounds during a 12‐year period. Of the 80,144 men enrolled, 31,866 men were randomized to the screening arm (SA) and invited for screening with prostate‐specific antigen test (cut‐off 4.0 ng/ml) every 4 years, while the remaining men formed the control arm (CA) that received no interventions. The mean follow‐up time for PC incidence in both arms was over 9 years. The incidence rate of PC (including screen‐detected and interval cancers as well as cases among nonparticipants) was 9.1 per 1,000 person‐years in the SA and 6.2 in the CA, yielding an incidence rate ratio (IRR) 1.5 (95% confidence interval 1.4–1.5). The incidence of advanced PC was 1.1 in the SA and 1.5 in the CA, IRR = 0.7 (0.6–0.8) and the difference emerges after 5–6 years of follow‐up. The incidence of localized PC was 7.5 in the SA and 4.6 in the CA, IRR = 1.6 (1.5–1.7). The results from our large population‐based trial indicate that screening for PC decreases the incidence of advanced PC. When compared with the CA, the PC detected in the SA there were substantially more often localized, low‐grade PCs due to overdiagnosis.     

Identification of an anti-idiotypic antibody that defines a B-cell subset(s) producing xenoantibodies in primates

Synthetic anti-idiotypic antibodies represent a potentially valuable tool for the isolation and characterization of B cells that produce xenoantibodies. An anti-idiotypic antibody that binds to a subset of B cells producing antibodies encoded by the variable-region heavy chain 3 (V(H)3) germline genes DP35 [immunoglobulin variable-region heavy chain 3-11 (IGHV3-11)], DP-53 and DP-54 plus a small number of V(H)4 gene-encoded antibodies in humans has recently been identified. These germline progenitors also encode xenoantibodies in humans. We tested whether the small, clearly defined group of B cells identified with this anti-idiotypic antibody produce xenoantibodies in non-human primates mounting active immune responses to porcine xenografts. Peripheral blood B cells were sorted by flow cytometry on the basis of phenotype, and cDNA libraries were prepared from each of these sorted groups of cells. Immunoglobulin V(H) gene libraries were prepared from the sorted cells, and the V(H) genes expressed in each of the sorted groups were identified by nucleic acid sequencing. Our results indicate that xenoantibody-producing peripheral blood B cells, defined on the basis of binding to fluorescein isothiocyanate (FITC)-conjugated galactose alpha(1,3) galactose-bovine serum albumin (Gal-BSA) and the anti-idiotypic antibody 2G10, used the IGHV3-11 germline gene to encode xenoantibodies and were phenotypically CD11b+ (Mac-1+) and CD5-. This novel reagent may be used in numerous applications including definition of xenoantibody-producing B-cell subsets in humans and non-human primates and immunosuppression by depletion of B cells producing anti-Gal xenoantibodies.