SUMMARY While chromosomal rearrangements fusing the androgen-regulated gene TMPRSS2 to the oncogenic ETS transcription factor ERG occur in approximately 50% of prostate cancers, how the fusion products regulate prostate cancer remains unclear. Using chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-Seq), we found that ERG disrupts androgen receptor (AR) signaling by inhibiting AR expression, binding to and inhibiting AR activity at gene-specific loci, and inducing repressive epigenetic programs via direct activation of the H3K27 methyltransferase EZH2, a Polycomb group protein. These findings provide a working model in which TMPRSS2-ERG plays a critical role in cancer progression by disrupting lineage-specific differentiation of the prostate and potentiating the EZH2-mediated de-differentiation program.
We have identified an unusual group of viridans group streptococci that resemble Streptococcus pneumoniae. DNA-DNA homology studies suggested that a subset of these isolates represent a novel species that may be included in the S. oralis-S. mitis group of viridans group streptococci. We suggest that this novel species be termed Streptococcus pseudopneumoniae. A combination of phenotypic and genetic reactions allows its identification. S. pseudopneumoniae strains do not have pneumococcal capsules, are resistant to optochin (inhibition zones, less than 14 mm) when they are incubated under an atmosphere of increased CO 2 but are susceptible to optochin (inhibition zones, >14 mm) when they are incubated in ambient atmospheres, are not soluble in bile, and are positive by the GenProbe AccuProbe Pneumococcus test. The bile solubility test is more specific than the optochin test for identification of S. pneumoniae. Genetic tests for pneumolysin (ply) and manganesedependent superoxide dismutase (sodA) and identification tests with a commercial probe, AccuProbe Pneumococcus, do not discriminate between the new species and S. pneumoniae.Streptococcus pneumoniae is the most common cause of community-acquired pneumonia and is also associated with bacteremia, meningitis, otitis media, and sinusitis, accounting for approximately 3,000 cases of meningitis, 50,000 cases of bacteremia, 500,000 cases of pneumonia, and 7 million cases of otitis media each year in the United States (1). Clinical laboratories must be able to accurately differentiate S. pneumoniae from other viridans group streptococci commonly found in clinical samples. An inability to correctly identify S. pneumoniae may result in inappropriate antimicrobial therapy.S. pneumoniae is a member of the Streptococcus mitis-Streptococcus oralis group (the Smit group) of viridans group streptococci, which includes S. mitis, S. oralis, Streptococcus cristatus, Streptococcus infantis, and Streptococcus peroris. Differentiation of S. pneumoniae from other viridans group streptococci, including members of the Smit group, has conventionally been based on phenotypic characteristics, most commonly by demonstrating optochin (OPT) susceptibility and/or solubility in bile (sodium deoxycholate) (18). Identification by these two tests is satisfactory when isolates from sterile sites are tested (16). However, identification is often problematic when samples from nonsterile sites, such as respiratory samples, are tested. The results of phenotypic testing can result in ambiguous OPT susceptibility and bile solubility (BS) test results (18).Although they are uncommon, OPT resistance has been reported in S. pneumoniae and OPT-resistant subpopulations have also been reported, both of which may lead to problems in identification, especially in association with atypical colony morphologies (4,13,36,42,45,46,55,60). Gardam and Miller (21) reported that variances in OPT zone sizes are dependent on the test medium and incubation environment used, as some media and environments may result in f...
Definitive diagnosis of leptospirosis has traditionally depended upon the isolation of leptospires from clinical specimens or the demonstration of seroconversion in paired acute and convalescent serum samples. Both of these approaches require expertise not routinely available in clinical laboratories and usually result in delayed diagnosis. Conventional PCR assays have been developed, but all have limitations which have restricted their widespread use. In order to overcome these limitations, a realtime PCR assay was developed using a 423 bp target on the lipL32 gene, which is conserved among pathogenic serovars of Leptospira. Reactions were monitored by SYBR green fluorescence and melting curve analysis. Representative serovars from 16 species of Leptospira and over 40 species of other bacteria and fungi were tested. Positive results were obtained with all pathogenic leptospiral serovars, with the exception of Leptospira fainei serovar Hurstbridge. The analytical sensitivity of this assay was 3 genome equivalents per reaction; approximately 10 genome equivalents were detectable in human urine. Leptospiral DNA was amplified from blood containing EDTA or citrate anticoagulants, but heparin, sodium polyanetholesulfonate and saponin were inhibitory. The assay successfully detected leptospiral DNA from serum and urine samples of patients with leptospirosis. This assay has the potential to facilitate rapid, sensitive diagnosis of acute leptospirosis.
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