Biomedical subjects

Lynn Wood

Publications and source records attributed to Lynn Wood.

3 recordsLinked to original sources

PubMed2005

Polyurethane biocidal polymeric surface modifiers.

Polyurethanes (PUs) with soft blocks containing semifluorinated (-CH2OCH2CF3) and 5,5-dimethylhydantoin pendant groups were prepared and employed (2 wt%) as biocidal polymeric surface modifiers (PSMs) for a conventional PU coating comprised of an isophorone diisocyanate/1,4-butanediol-derived hard block (50%) and poly(tetramethylene oxide) soft block. Surface enrichment of the PSM was verified by dynamic contact angle measurements. The PSM modified PU was activated by converting near-surface amide groups to chloramide with 3wt% hypochlorite. The conversion of near-surface amide to chloramide is reflected in somewhat increased hydrophobic character for the antimicrobial chloramide functionalized surfaces. Biocidal activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa, and Escherichia coli) bacteria was demonstrated by using a modified version of American Association of Textile Chemists and Colorists (AATCC-100) test. By changing the PSM concentration it was found that only 1.6 wt% PSM (0.66 wt% biocide, 5,5-dimethylhydantoin) in a conventional PU affected complete kill of P. aeruginosa in 15 min by using this biocidal testing protocol.

Anti-Infective Agents↗

PubMed2005

E-ring modified steroids as novel potent inhibitors of 17beta-hydroxysteroid dehydrogenase type 1.

17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) are an important class of steroidogenic enzymes that regulate the bioavailability of active estrogens and androgens and are as yet a relatively unexploited therapeutic target. Based on our investigations and those of others, E-ring modified steroids were identified as a useful template for the design of inhibitors of 17beta-HSD type 1, an enzyme involved in the conversion of estrone into estradiol. The synthesis and biological evaluation of a new series of N- and C-substituted 1,3,5(10)-estratrien-[17,16-c]-pyrazoles and the corresponding SAR are discussed. Among the N-alkylated analogues, the most potent inhibitor was the 1'-methoxyethyl derivative, 41, with an IC(50) of 530 nM in T47-D human breast cancer cells. The X-ray crystal structure of the 1'-isobutyl derivative, was determined. Further optimization of the template using parallel synthesis resulted in a library of C5'-linked amides from which 73 emerged. This pyridylethyl amide had an IC(50) of 300 nM and its activity, with that of 41, suggests the importance of hydrogen bond acceptor groups in the pyrazole side chain. Both 41 and 73 displayed selectivity over 17beta-HSD type 2, and preliminary investigations showed 41 to be nonestrogenic in vitro in a luciferase reporter gene assay in contrast to the parent pyrazole 25. Molecular modeling studies, which support these findings, and a QSAR, the predictive power of which was demonstrated, are also presented.

17-Hydroxysteroid Dehydrogenases↗

PubMed2003

The nuclear BAG-1 isoform, BAG-1L, enhances oestrogen-dependent transcription.

BAG-1 is a multifunctional protein that interacts with a wide range of cellular targets including heat-shock proteins and some nuclear hormone receptors. BAG-1 exists as three major isoforms, BAG-1L, BAG-1M and BAG-1S. BAG-1L contains a nuclear localization signal, which is not present in the other isoforms, and is predominantly localized in the cell nucleus. Here we have investigated the effects of BAG-1 on function of the oestrogen receptor (ER), a key growth control molecule and target for hormonal therapy in breast cancer. We demonstrate that BAG-1L, but not BAG-1S or BAG-1M, increased oestrogen-dependent transcription in breast cancer cells. BAG-1L interacted with and stimulated the activity of both ER alpha and beta. Although BAG-1L and ERs colocalize to the nucleus, fusing BAG-1S to an heterologous nuclear localization sequence was not sufficient to stimulate transcription. Consistent with an important effect on receptor function, nuclear BAG-1 expression in breast cancers was associated with expression of the progesterone receptor, a transcriptional target of ERalpha, and was associated with improved survival in patients treated with hormonal therapy. These data suggest that BAG-1L is an important determinant of ER function in vitro and in human breast cancer.

Breast Neoplasms↗