Adenoid cystic carcinoma of the thymus gland.

BACKGROUND: Thymic carcinomas are rare and aggressive tumours. They constitute a heterogeneous group of tumours with various histological patterns and subtypes resembling epithelial tumours arising from other organs. CASE PRESENTATION: We hereby represent a case of primary thymic carcinoma with adenoid cystic carcinoma-like features (TCACC) which is an extremely rare variant of thymic adenocarcinoma. To date and to the best of our knowledge, there are nine reported cases in literature and ours is the tenth. Our case was treated surgically but the implementation of adjuvant chemoradiotherapy has been reported in few of the published cases. CONCLUSIONS: TCACC constitutes a rare entity of thymic adenocarcinoma with limited available literature. The current data is derived from few case reports and case series. The histological overlap of these tumours and primary ACC of salivary glands poses a diagnostic challenge. Radiological investigations, immunohistochemical phenotyping and genetic analysis are crucial in establishing the diagnosis.

Cytotoxicity Comparison between Drinking Water Treated by Chlorination with Postchloramination versus Granular Activated Carbon (GAC) with Postchlorination.

Granular activated carbon treatment with postchlorination (GAC/Cl2) and chlorination followed by chloramination (Cl2/NH2Cl) represent two options for utilities to reduce DBP formation in drinking water. To compare the total cytotoxicity of waters treated by a pilot-scale GAC treatment system with postchlorination (and in some instances with prechlorination upstream of GAC (i.e., (Cl2)/GAC/Cl2)) and chlorination/chloramination (Cl2/NH2Cl) at ambient and elevated Br- and I- levels and at three different GAC ages, we applied the Chinese hamster ovary (CHO) cell cytotoxicity assay to whole-water extracts in conjunction with calculations of the cytotoxicity contributed by the 33 (semi)volatile DBPs lost during extractions. At both ambient and elevated Br- and I- levels, GAC/Cl2 and Cl2/NH2Cl achieved comparable reductions in the formation of regulated trihalomethanes (THMs) and haloacetic acids (HAAs). Nonetheless, GAC/Cl2 always resulted in lower total cytotoxicity than Cl2/NH2Cl, even at up to 65% total organic carbon breakthrough. Prechlorination formed (semi)volatile DBPs that were removed by the GAC, yet there was no substantial difference in total cytotoxicity between Cl2/GAC/Cl2 and GAC/Cl2. The poorly characterized fraction of DBPs captured by the bioassay dominated the total cytotoxicity when the source water contained ambient levels of Br- and I-. When the water was spiked with Br- and I-, the known, unregulated (semi)volatile DBPs and the uncharacterized fraction of DBPs were comparable contributors to total cytotoxicity; the contributions of regulated THMs and HAAs were comparatively minor.

Bench-scale column evaluation of factors associated with changes in N-nitrosodimethylamine (NDMA) precursor concentrations during drinking water biofiltration.

Biofiltration has been observed to increase or decrease the concentrations of N-nitrosodimethylamine (NDMA) precursors in the effluents of full-scale drinking water facilities, but these changes have been inconsistent over time. Bench-scale tests comparing biofiltration columns side-by-side exposed to different conditions were employed to characterize factors associated with changes in NDMA precursor concentrations, as measured by application of chloramines under uniform formation conditions (UFC). Side-by-side comparisons of biofiltration media from different facilities fed with water from each of these facilities demonstrated that differences in source water quality were far more important than any original differences in the microbial communities on the biofiltration media for determining whether NDMA precursor concentrations increased, decreased or remained constant across biofilters. Additional tests involving spiking of specific constituents hypothesized to promote increases in NDMA precursor concentrations demonstrated that inorganic nitrogen species associated with nitrification, including ammonia, hydroxylamine and chloramines, and biotransformation of known precursors (i.e., municipal wastewater and the cationic polymer, polyDADMAC) to more potent forms were not important. Biotransformation of uncharacterized components of source waters determined whether NDMA precursor concentrations increased or decreased across biofilters. These uncharacterized source water component concentrations varied temporally and across locations. Where biotransformation of source water precursors increased NDMA precursor concentrations, ∼30-60% of the levels observed in column effluents fed with biofiltration influent water remained associated with the media and could be rinsed therefrom in either the dissolved or particulate form. Ozone pre-treatment significantly reduced NDMA precursor concentrations at one facility, suggesting that pre-oxidation could be an effective technique to mitigate the increase in NDMA precursor concentrations during biofiltration. Biofiltration decreased the concentrations of halogenated disinfection byproduct precursors.

Effect of softening precipitate composition and surface characteristics on natural organic matter adsorption.

Natural organic matter (NOM) removal during water softening is thought to occur through adsorption onto or coprecipitation with calcium and magnesium solids. However, details of precipitate composition and surface chemistry and subsequent interactions with NOM are relatively unknown. In this study, zeta potentiometry analyses of precipitates formed from inorganic solutions under varying conditions (e.g., Ca-only, Mg-only, Ca + Mg, increasing lime or NaOH dose) indicated that both CaCO3 and Mg(OH)2 were positively charged at higher lime (Ca(OH)2) and NaOH doses (associated with pH values above 11.5), potentially yielding a greater affinity for adsorbing negatively charged organic molecules. Environmental scanning electron microscopy (ESEM) images of CaCO3 solids illustrated the rhombohedral shape characteristic of calcite. In the presence of increasing concentrations of magnesium, the CaCO3 rhombs shifted to more elongated crystals. The CaCO3 solids also exhibited increasingly positive surface charge from Mg incorporation into the crystal lattice, potentially creating more favorable conditions for adsorption of organic matter. NOM adsorption experiments using humic substances extracted from Lake Austin and Missouri River water elucidated the role of surface charge and surface area on adsorption.

Structure of IL-17A in complex with a potent, fully human neutralizing antibody.

IL-17A is a pro-inflammatory cytokine produced by the newly identified Th17 subset of T-cells. We have isolated a human monoclonal antibody to IL-17A (CAT-2200) that can potently neutralize the effects of recombinant and native human IL-17A. We determined the crystal structure of IL-17A in complex with the CAT-2200 Fab at 2.6 A resolution in order to provide a definitive characterization of the epitope and paratope regions. Approximately a third of the IL-17A dimer is disordered in this crystal structure. The disorder occurs in both independent copies of the complex in the asymmetric unit and does not appear to be influenced by crystal packing. The complex contains one IL-17A dimer sandwiched between two CAT-2200 Fab fragments. The IL-17A is a disulfide-linked homodimer that is similar in structure to IL-17F, adopting a cystine-knot fold. The structure is not inconsistent with the previous prediction of a receptor binding cavity on IL-17 family members. The epitope recognized by CAT-2200 is shown to involve 12 amino acid residues from the quaternary structure of IL-17A, with each Fab contacting both monomers in the dimer. All complementarity-determining regions (CDRs) in the Fab contribute to a total of 16 amino acid residues in the antibody paratope. In vitro affinity optimization was used to generate CAT-2200 from a parental lead antibody using random mutagenesis of CDR3 loops. This resulted in seven amino acid changes (three in VL-CDR3 and four in VH-CDR3) and gave an approximate 30-fold increase in potency in a cell-based neutralization assay. Two of the seven amino acids form part of the CAT-2200 paratope. The observed interaction site between CAT-2200 and IL-17A is consistent with data from hydrogen/deuterium exchange mass spectrometry and mutagenesis approaches.

Urinary nandrolone metabolite detection after ingestion of a nandrolone precursor.

INTRODUCTION: Quantities of various anabolic/androgenic steroids have been found in dietary supplements without their presence being disclosed on the label. The aim of this study was to quantify the excretion patterns of the diagnostic metabolites, 19-norandrosterone (19-NA), and 19-noretiocholanolone (19-NE) after ingestion of small doses of 19-nor-4-androstene-3,17-dione (19-norandrostenedione). METHODS: Eleven males and nine females entered the laboratory in the morning after an overnight fast. An initial urine sample was collected, and volunteers then ingested 500 mL of water containing 5 g of creatine monohydrate and 1.0, 2.5, or 5.0 microg of 19-norandrostenedione. The volume of each urine void was measured, and an aliquot was taken. Samples were analyzed for the metabolites 19-NA and 19-NE by GCMS. RESULTS: Baseline urinary 19-NA concentrations were 0.19 +/- 0.14 ng x mL. Ingestion of the supplement resulted in peak mean urinary 19-NA concentrations of 0.68 +/- 0.36, 1.56 +/- 0.86, and 3.89 +/- 3.11 ng.mL in the 1.0-, 2.5-, or 5.0-microg trials, respectively. Under current WADA regulations, ingestion of the 1.0-microg dose produced 0 positive doping tests, 5 subjects (20%) tested positive in the 2.5-microg trial, and 15 subjects (75%) had urinary 19-NA concentrations exceeding 2 ng x mL after ingesting creatine containing 5.0 microg of the steroid. The recovery of the ingested dose was highly variable between individuals, with values ranging from 11% to 84% (mean +/- SD = 47% +/- 18%). CONCLUSIONS: Ingestion of trace amounts of 19-norandrostenedione can result in transient elevations of urinary 19-NA and 19-NE concentrations. The addition of as little as 2.5 microg of 19-norandrostenedione to a supplement (0.00005% contamination) appears sufficient to result in a doping violation in some individuals.

Identification and characterization of Prp45p and Prp46p, essential pre-mRNA splicing factors.

Through exhaustive two-hybrid screens using a budding yeast genomic library, and starting with the splicing factor and DEAH-box RNA helicase Prp22p as bait, we identified yeast Prp45p and Prp46p. We show that as well as interacting in two-hybrid screens, Prp45p and Prp46p interact with each other in vitro. We demonstrate that Prp45p and Prp46p are spliceosome associated throughout the splicing process and both are essential for pre-mRNA splicing. Under nonsplicing conditions they also associate in coprecipitation assays with low levels of the U2, U5, and U6 snRNAs that may indicate their presence in endogenous activated spliceosomes or in a postsplicing snRNP complex.