Development of methods for the detection of trace amounts of selected carcinogenic and mutagenic amines in water

A great deal of concern exists over the presence of potentially carcinogenic and/or mutagenic substances in drinking water supplies. The general analytical schemes currently applied to water are less suited than specific methods for the detection of certain classes of organic contaminants such as aromatic amines because of their reactivity. We have concentrated our efforts at developing analytical schemes by which we are able to reliably detect, separate, and quantitate trace levels of a number of aromatic and heterocyclic amines. Both liquid and gas chromatographic methods have been developed. The relative strengths and limitations of the methods are discussed. Field evaluations of the final methods were carried out and reported.U.S. Department of the InteriorU.S. Geological SurveyOpe

Face-to-face: Social work and evil

The concept of evil continues to feature in public discourses and has been reinvigorated in some academic disciplines and caring professions. This article navigates social workers through the controversy surrounding evil so that they are better equipped to acknowledge, reframe or repudiate attributions of evil in respect of themselves, their service users or the societal contexts impinging upon both. A tour of the landscape of evil brings us face-to-face with moral, administrative, societal and metaphysical evils, although it terminates in an exhortation to cultivate a more metaphorical language. The implications for social work ethics, practice and education are also discussed

R-h-erythropoietin counteracts the inhibition of in vitro erythropoiesis by tumour necrosis factor alpha in patients with rheumatoid arthritis

Anaemia of chronic disease (ACD) is a common extra-articular manifestation of rheumatoid arthritis (RA). Tumour necrosis factor alpha (TNFα) plays an important role in the development of ACD. The objective of the present study was to assess inhibition of in vitro colony-forming unit erythrocyte (CFUe) and blast-forming unit erythrocyte (BFUe) growth by TNFα and to examine whether this suppression could be counteracted by adding increasing concentrations of recombinant human erythropoietin (EPO) (r-h-EPO) to bone marrow cultures of RA patients with ACD and without anaemia (controls). Bone marrow cells of RA patients with ACD and control patients were cultured. The cultures were incubated with increasing concentrations of r-h-EPO (0.25; 0.5; 1; 2 U/ml), each in combination with increasing quantities of TFNα (0; 50; 100; 200; 400 U/ml). CFUe and BFUe were assessed after 7 and 14 days, respectively. Dose-dependent inhibition of BFUe and CFUc by increasing concentrations of TNFα was observed in ACD and controls. Regarding CFUe (ACD patients) incubated with 0.25 U/ml EPO, 50 U/ml TNFα caused 28% suppression compared to cultures without TNFα. Increasing the concentration of r-h-EPO from 0.25 U/ml to 2 U/ml completely restored the number of CFUe. A similar pattern was observed in BFUe growth in both groups. These data demonstrated the suppressive effects of TNFα on erythropoiesis in vitro and that the suppresed erythropoiesis could be partly corrected by the addition of excess r-h-EPO to the cultures. No significant differences were observed between ACD and control RA patients. This in vitro model may help explain the clinical response to r-h-EPO therapy as documented in RA patients with ACD

Highly Polarized Optically-Selected BL Lacertae Objects

Observations of candidate BL Lacertae objects spectroscopically selected from the Sloan Digital Sky Survey (SDSS) reveal a large fraction with high polarization (P > 3%). This result confirms that synchrotron radiation makes an important contribution to the observed optical continuum for most objects in the sample. The SDSS sample can be divided into separate categories, with objects of undetermined redshift generally having the highest optical polarization. Polarization as high as 23% and the lack of spectral features suggests that the synchrotron continuum completely dominates the spectra of these sources. The mean polarization levels observed for objects having measured redshifts is much lower, with the maximum observed polarization for this group being ~10%. The lower polarizations of these objects are reminiscent of the less spectacular polarization levels shown by BL Lac objects discovered in X-ray surveys. We find no SDSS BL Lac candidates at z > 1 with P > 3%, calling their classification as BL Lac objects into question. In addition, the existence of radio-quiet BL Lac objects is not verified since none of 10 potentially radio-weak BL Lac candidates observed are highly polarized. Regardless of whether the high-redshift and radio-weak objects are included in this optical sample, the overall levels of polarization observed are intermediate between those seen for X-ray and radio-selected BL Lac objects.Comment: 9 pages, 3 figures, 2 table

Import of cytochrome c into mitochondria

The import of cytochrome c into mitochondria can be resolved into a number of discrete steps. Here we report on the covalent attachment of heme to apocytochrome c by the enzyme cytochrome c heme lyase in mitochondria from Neurospora crassa. A new method was developed to measure directly the linkage of heme to apocytochrome c. This method is independent of conformational changes in the protein accompanying heme attachment. Tryptic peptides of [35S]cysteine-labelled apocytochrome c, and of enzymatically formed holocytochrome c, were resolved by reverse-phase HPLC. The cysteine-containing peptide to which heme was attached eluted later than the corresponding peptide from apocytochrome c and could be quantified by counting 35S radioactivity as a measure of holocytochrome c formation. Using this procedure, the covalent attachment of heme to apocytochrome c, which is dependent on the enzyme cytochrome c heme lyase, could be measured. Activity required heme (as hemin) and could be reversibly inhibited by the analogue deuterohemin. Holocytochrome c formation was stimulated 5–10-fold by NADH > NADPH > glutathione and was independent of a potential across the inner mitochondrial membrane. NADH was not required for the binding of apocytochrome c to mitochondria and was not involved in the reduction of the cysteine thiols prior to heme attachment. Holocytochrome c formation was also dependent on a cytosolic factor that was necessary for the heme attaching step of cytochrome c import. The factor was a heat-stable, protease-insensitive, low-molecular-mass component of unknown function. Cytochrome c heme lyase appeared to be a soluble protein located in the mitochondrial intermembrane space and was distinct from the previously identified apocytochrome c binding protein having a similar location. A model is presented in which the covalent attachment of heme by cytochrome c heme lyase also plays an essential role in the import pathway of cytochrome c

Epithelial Tissues Have Varying Degrees of Susceptibility to KrasG12D-Initiated Tumorigenesis in a Mouse Model

Activating mutations in the Kras gene are commonly found in some but not all epithelial cancers. In order to understand the susceptibility of different epithelial tissues to Kras-induced tumorigenesis, we introduced one of the most common Kras mutations, KrasG12D, broadly in epithelial tissues. We used a mouse model in which the G12D mutation is placed in the endogenous Kras locus controlled by inducible, Cre-mediated recombination in tissues expressing cytokeratin 19 including the oral cavity, GI tract, lungs, and ducts of the liver, kidney, and the pancreas. Introduction of the KrasG12D mutation in adult mouse tissues led to neoplastic changes in some but not all of these tissues. Notably, many hyperplasias, metaplasias and adenomas were observed in the oral cavity, stomach, colon and lungs, suggesting that exposure to products of the outside environment promotes KrasG12D-initiated tumorigenesis. However, environmental exposure did not consistently correlate with tumor formation, such as in the small intestine, suggesting that there are also intrinsic differences in susceptibility to Kras activation. The pancreas developed small numbers of mucinous metaplasias with characteristics of early stage pancreatic intraepithelial neoplasms (PanINs), supporting the hypothesis that pancreatic ducts have the potential to give rise pancreatic cancer