Organochlorine Contaminants of Wintering Ducks Foraging on Detroit River Sediments

Organochlorine analysis was performed on carcasses of 13 diving ducks from a 1981 wintering population that foraged on contaminated sediments in the lower Detroit River. Mean total PCB concentrations were 10 mg/kg for seven lesser scaups (Aythya affinis), 11 mg/kg for three greater scaups (A. marila), and 7.6 mg/kg for three goldeneyes (Bucephala clangula). Highest mean levels of other residues were measured for hexachlorobenzene (1.7 mg/kg) in goldeneyes, and transnonachlor (0.33 mg/kg) and 4,4’-DDE (1.3 mg/kg) in greater scaup. Quantitative analysis of 72 PCB congeners also was applied to water, seston, sediment, benthie oligochaetes, and carp from the same site. Principal congeners in most of the samples included some of the more toxic and persistent PCBs. Results of a multivariate analysis indicated that ratios of more conservative to less conservative PCBs did not vary significantly among ducks (α = .05), but differed from those in carp, oligochaetes, and sediment. For the February through March period of fat mobilization, concentrations of total PCB in lipid were inversely correlated with percent lipid (r = 0.76) in ducks. The percentage of conservative PCBs increased slightly. The distribution and partitioning of organochlorines, including toxic PCB congeners, varied considerably within this water column-sediment-fauna ecosystem. Estimates of toxic exposure based on total PCB values may be unreliable.     

Event-related potentials to inspiratory flow-resistive loads in young adults: stimulus magnitude effects

Event-related potentials were recorded to brief presentations of four levels of inspiratory flow-resistive loads in young adults. We labeled the loads according to the level of resistance they provided subjectively: sub-threshold (0.34 cmH2O/l per s), near-threshold (4.01 cmH2O/l per s), intermediate (10.4cmH2O/l per s), and near-occlusion (57.5 cmH2O/l per s). No discernible ERPs were elicited by the undetected, sub-threshold stimulus but late components of the ERP (P2, N2, and P3) were observed to each of the three larger stimuli. They were related, in part, to behavioral judgments obtained during the stimulus periods. Both the latency and amplitude of the ERP components varied systematically as a function of stimulus magnitude, in a manner comparable to that observed in ERP paradigms using auditory and visual stimuli. Thus, the data show that event-related potentials to breathing are sensitive to physiologic effects of resistive loads present at the onset of inspiration. Respiratory ERPs may be used to infer sensory and perceptual responses to increases in airflow resistance and, accordingly, may relate to the perception of airflow obstruction in patient populations.     

Integrated radiation hybrid and yeast artificial chromosome map of chromosome 9p

OBJECTIVES: To determine concentrations of chondroitin sulphate (CS) and keratan sulphate (KS) epitopes, glycosaminoglycans (GAGs) and hyaluronan (HA) in knee synovial fluid (SF) from normal subjects and patients with osteoarthritis (OA) or rheumatoid arthritis (RA), to test whether these variables may be used as markers of the OA process. METHODS: OA was subdivided into large joint OA (LJOA), nodal generalised OA (NGOA), and OA with calcium pyrophosphate crystal deposition (CPA). Clinical assessment of inflammation (0-6) was undertaken on OA and RA knees. Knee SF was examined by enzyme linked immunosorbent assay for: CS epitopes, using monoclonal antibodies 3-B-3 and 7-D-4; KS epitope using monoclonal antibody 5-D-4; and HA, using biotinylated HA binding region of cartilage proteoglycan. Total sulphated GAGs were measured by dye binding with 1:9 dimethylmethylene blue. RESULTS: Increased SF 3-B-3 concentrations and 3-B-3/GAG ratio were found in OA, compared with RA or normal knees, with higher 3-B-3 and 3-B-3/GAG in LJOA and NGOA than in CPA. SF 7-D-4 and 7-D-4/GAG were reduced in RA, compared with normal and OA; SF 5-D-4 was reduced in OA compared with normal. GAG and HA concentrations were decreased in both OA and RA. No correlations with radiographic scores were observed, but SF 7-D-4 was lower in 'inflamed' compared with 'non-inflamed' RA and OA knees. In patients with bilateral samples there were strong correlations between right and left knees for all SF variables. CONCLUSIONS: Changed concentrations of SF CS and KS can be detected in OA with a profile that differs from that seen in RA. Clinical subgrouping and local joint inflammation may influence these measures, supporting different pathogenesis within OA subgroups and requirement for careful patient characterisation in SF studies.     

The abrasive wear of metals

A quite general relationship exists between abrasive wear and the ploughing contribution to friction. Tensile stresses are developed in the material displaced by the ploughing indenter and these give rise to wear particles.     

Targeting tumour proliferation with a small-molecule inhibitor of AICAR transformylase homodimerization

Aminoimidazole carboxamide ribonucleotide transformylase/ inosine monophosphate cyclohydrolase (ATIC) is a bifunctional homodimeric enzyme that catalyzes the last two steps of de novo purine biosynthesis. Homodimerization of ATIC, a protein–protein interaction with an interface of over 5000 Ų, is required for its aminoimidazole carboxamide ribonucleotide (AICAR) transformylase activity, with the active sites forming at the interface of the interacting proteins. Here, we report the development of a small‐molecule inhibitor of AICAR transformylase that functions by preventing the homodimerization of ATIC. The compound is derived from a previously reported cyclic hexapeptide inhibitor of AICAR transformylase (with a K_i of 17 μM ), identified by high‐throughput screening. The active motif of the cyclic peptide is identified as an arginine‐tyrosine dipeptide, a capped analogue of which inhibits AICAR transformylase with a K_i value of 84 μM . A library of nonnatural analogues of this dipeptide was designed, synthesized, and assayed. The most potent compound inhibits AICAR transformylase with a K_i value of 685 nM , a 25‐fold improvement in activity from the parent cyclic peptide. The potential for this AICAR transformylase inhibitor in cancer therapy was assessed by studying its effect on the proliferation of a model breast cancer cell line. Using a nonradioactive proliferation assay and live cell imaging, a dose‐dependent reduction in cell numbers and cell division rates was observed in cells treated with our ATIC dimerization inhibitor.