Biology of chronic radiation effect on tissues and wound healing

Radiation therapy exerts both acute and chronic effects on normal tissue included within treatment fields. The physics of radiation therapy and treatment techniques to minimize deleterious effects of radiation are presented. Management of radiation-damaged skin is discussed. Radiation effect on tissue, wound healing, and tumorigenesis also are reviewed.     

First evaluation of a year of ambulatory surgery in urology

Day surgery in urology is in full growth actually. The present report is based on our first 120 patients. Low post-operative complication rate, patients' satisfaction and economical savings are the main factors for the important increase in this type of surgery.     

The Pol beta-14 dominant negative rat DNA polymerase beta mutator mutant commits errors during the gap-filling step of base excision repair in Saccharomyces cerevisiae

We demonstrated recently that dominant negative mutants of rat DNA polymerase beta (Pol beta) interfere with repair of alkylation damage in Saccharomyces cerevisiae. To identify the alkylation repair pathway that is disrupted by the Pol beta dominant negative mutants, we studied the epistatic relationship of the dominant negative Pol beta mutants to genes known to be involved in repair of DNA alkylation damage in S. cerevisiae. We demonstrate that the rat Pol beta mutants interfere with the base excision repair pathway in S. cerevisiae. In addition, expression of one of the Pol beta dominant negative mutants, Pol beta-14, increases the spontaneous mutation rate of S. cerevisiae whereas expression of another Pol beta dominant negative mutant, Pol beta-TR, does not. Expression of the Pol beta-14 mutant in cells lacking APN1 activity does not result in an increase in the spontaneous mutation rate. These results suggest that gaps are required for mutagenesis to occur in the presence of Pol beta-14 but that it is not merely the presence of a gap that results in mutagenesis. Our results suggest that mutagenesis can occur during the gap-filling step of base excision repair in vivo.     

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.     

Response of dermal fibroblast cultures from patients with unusually severe responses to radiotherapy and from ataxia telangiectasia heterozygotes to fractionated radiation

We examined the cytotoxic effects of radiation delivered in daily fractions at clinically relevant doses in plateau phase cultures of skin fibroblast cell strains derived from ataxia telangiectasia (AT) heterozygotes, patients with unusually sensitive responses to radiotherapy, apparently normal patients, and cell bank controls. A gradual linear reduction in surviving fraction versus total dose was observed in the control group, comprised of apparently normal individuals and one patient with a normal clinical response to radiotherapy, after exposure to daily fractions of 2.0 Gy. There was a much steeper decline in surviving fraction among the AT heterozygotes and the group with sensitive responses to radiotherapy, such that after six daily fractions of 2.0 Gy (12 Gy total dose), the mean surviving fraction of the control group was significantly different from that of the AT heterozygotes (P = 0.0009) and that of the patients with unusually sensitive responses to radiotherapy (P = 0.0002). We propose that this assay may be a useful means of identifying cell strains from AT heterozygotes. Based on these results, the hypothesis is discussed that patients who suffer unusually sensitive clinical reactions to radiotherapy may be AT heterozygotes.