Molecular interaction of [2,3-14C] acrylonitrile with DNA in gastric tissue of rat

Acrylonitrile (VCN) is used extensively in polymer industries, and is known to induce gastric cancer following oral administration. A paucity of information exists regarding the mechanism(s) by which acrylonitrile induces gastric neoplasia. The time course for uptake of radioactivity by gastric tissue and covalent binding of [2,3-14C] VCN or its metabolites to gastric DNA were determined following a single oral dose of 46.5 mg/kg. The rates of DNA synthesis and repair, as measured by unscheduled DNA synthesis in the gastric tissue of VCN-treated rats, were also studied. Maximum tissue uptake and covalent binding of radioactivity to gastric DNA were observed at 15 minutes following [2,3-14C] VCN administration. At 6 hours following VCN administration, significant inhibition (37% of control) in gastric replicative DNA synthesis was observed. A rebound followed by an increase (211% of control) in replicative DNA synthesis was observed at 24 hours. A three-fold elevation in unscheduled DNA synthesis was observed at 24 hours following treatment with VCN. These results indicate that VCN or its metabolites irreversibly interact with gastric DNA, causing DNA damage. The results also indicate that the delayed VCN-induced DNA repair, determined as unscheduled DNA synthesis, is inefficient for the removal of the resulting DNA lesions.     

Visualisation of mass transport of small organic molecules and metal ions through articular cartilage by magnetic resonance imaging

Magnetic resonance imaging of water has been used to visualise the migration of three paramagnetic species, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (4-hydroxy-TEMPO, 1), Cu2+ ions, and copper ethylenediamine-tetraacetate (CuEDTA, 2) through cartilage on the femoral condyle of the chicken knee. The migration of copper ions is dominated by strong binding with the cartilage. In contrast, both 1 and 2 bind weakly, and their diffusion can be followed as a progressive wave through the cartilage and subsequently into the trabecular bone structure.     

11C-diprenorphine binding in Huntington''s disease: a comparison of region of interest analysis with statistical parametric mapping

The combination of specific gene targeting technologies with efficient gene delivery systems could provide the means to evaluate the concept of anticancer strategies designed to block expression of potentially rate-limiting tumor promoting factors. Here, we constructed adenoviruses expressing hammerhead-ribozymes targeted to two of these factors, the tyrosine kinase receptor HER-2/neu or the growth factor pleiotrophin (PTN). Adenovirus-mediated transduction of either HER-2/neu- or PTN-targeted ribozymes depleted the respective RNAs and inhibited protein expression significantly in three different human cancer cell lines. This resulted in almost complete abrogation of HER-2/neu- or PTN-dependent cancer-cell proliferation, thus demonstrating the feasibility of this approach as a future cancer gene therapy.     

A clinical advancement program: creating an environment for professional growth

Clinical ladders help maintain expert, motivated, and effective nurses in direct patient care roles. While many institutions were phasing out clinical ladders for registered nurses, Miami Valley Hospital was proactively evaluating the original version. The authors describe their clinical advancement program, based on Benner's model, with program evaluation results. The program participation rate has increased overall. Participants perceive their work and environment more positively than nonparticipants.     

Dyslexia, neurolinguistic ability, and anatomical variation of the planum temporale

This article addresses the relationship between patterns of planum temporale symmetry/asymmetry and dyslexia and neurolinguistic abilities. Considerable research indicates that dyslexic individuals typically do not display the predominant pattern of leftward planum temporale asymmetry. Variable findings on the structural basis of symmetry are due partially to measurement issues, which are examined in some detail in this critical review. The physiological basis of symmetry may be reduced neuronal elimination in the right planum, although other alternatives are offered. Theories are offered to explain how symmetrical plana are related to dyslexia, and it is evident that symmetrical plana are not sufficient to produce dyslexia. However, some evidence suggests that nonleftward plana asymmetry is associated with deficits in verbal comprehension, phonological decoding, and expressive language. It is concluded that nonleftward asymmetry is associated with linguistic deficits, but that explanatory theories need to be further developed. Among the many issues that need to be addressed, future research needs to determine whether the relationship between patterns of planum temporale symmetry/asymmetry and linguistic ability is specific to dyslexia or if asymmetry covaries lawfully with linguistic abilities in nondyslexic populations.