Prognostic significance of cathepsin-D in patients with breast cancer

The expression of the protease cathepsin-D has been evaluated using an immunohistochemical technique with a polyclonal antibody in paraffin-embedded tissue from 359 patients treated between the years 1975-1981 for Stage I and II breast cancer. One hundred and twenty seven patients (35%) have strongly positive, granular staining, 138 (38%) are intermediately stained in the cytoplasm, and in 94 (26%) no staining is observed. There is a strong positive association between expression of cathepsin-D and the presence of tumour in axillary lymph nodes (P < 0.006). Expression of the protease is associated with significantly poorer survival of patients in univariate analysis (P = 0.025); however, this is not independent of other tumour variables.     

RNA tertiary structure mediation by adenosine platforms

The crystal structure of a group I intron domain reveals an unexpected motif that mediates both intra- and intermolecular interactions. At three separate locations in the 160-nucleotide domain, adjacent adenosines in the sequence lie side-by-side and form a pseudo-base pair within a helix. This adenosine platform opens the minor groove for base stacking or base pairing with nucleotides from a noncontiguous RNA strand. The platform motif has a distinctive chemical modification signature that may enable its detection in other structured RNAs. The ability of this motif to facilitate higher order folding provides one explanation for the abundance of adenosine residues in internal loops of many RNAs.     

Multiple solution conformations of the integrin-binding cyclic pentapeptide cyclo(-Ser-D-Leu-Asp-Val-Pro-). Analysis of the (phi, psi) space available to cyclic pentapeptides

The aqueous solution structure of the cyclic pentapeptide cyclo(-Ser-D-Leu-Asp-Val-Pro-) has been determined by two-dimensional 1H-NMR spectroscopy, combined with a conformational search and distance-geometry calculations. As many as five conformers in slow exchange were observed, and the rate of interconversion between components was measured from the build-up rates of exchange peaks. NMR data allowed the structures of the two predominant conformers to be determined. The major component (66%) contained a cis-proline as part of a type-VIa2 beta-turn encompassing residues Asp-Val-cis-Pro-Ser. The second component (16%) contained only trans-amide bonds, and a type-VIII beta-turn formed by residues Val-Pro-Ser-D-Leu. These structures are discussed in relation to the (phi, psi), space available to the cyclic pentapeptide, determined by a conformational search, and in relation to previously published cyclic-pentapeptide structures. The molecule exhibits activity in a scintillation-proximity assay for the inhibition of the interaction between the integrin very-late antigen-4 (VLA-4; alpha 4 beta 1) and vascular-cell-adhesion molecule-1 (VCAM-1). The structure/activity relationship of the LDV sequence is discussed and related to the recently published X-ray structure of VCAM-1. The relevance of the work to the design of anti-inflammatory drugs is discussed.     

Foundations'' impact on policy making: results from a pilot study

Thirty-two consecutive patients with haematological disorders, in need of a permanent central venous catheter (CVC) were randomly allocated to have their CVC bandages (Tegaderm) changed once (OAW, n = 20) or twice (TAW, n = 19) a week. The two randomization arms were balanced in respect of age, sex, and underlying disease. The exit site of the CVC was inspected daily through the transparent bandage and erythema was noted. If severe erythema occurred, daily wet gauze dressings were applied. Samples for bacterial cultures were taken from the exit site of the CVC at every change of bandages. There was no difference in complications leading to removal of the CVC between the two groups (7/20 OAW vs. 7/19 TAW) or in CVC survival-time (P = 0.4). However, the OAW group had more positive CVC tip cultures (OAW 11/14 vs. TAW 2/9; P < 0.05) and a tendency to: (i) more extra dressings (P = 0.08); (ii) more cultures from the exit skin site showing high numbers of colony forming units (P = 0.07); (iii) shorter time to first exit site infection (P = 0.09); and (iv) more Gram-positive septicaemias (P = 0.08). Both clinical and bacteriological data in this study indicate that changing transparent polyurethane CVC bandages twice a week is superior to once a week.