Frequent clones of p53-mutated keratinocytes in normal human skin

The multiple genetic hit model of cancer predicts that normal individuals should have stable populations of cancer-prone, but noncancerous, mutant cells awaiting further genetic hits. We report that whole-mount preparations of human skin contain clonal patches of p53-mutated keratinocytes, arising from the dermal-epidermal junction and from hair follicles. These clones, 60-3000 cells in size, are present at frequencies exceeding 40 cells per cm2 and together involve as much as 4% of the epidermis. In sun-exposed skin, clones are both more frequent and larger than in sun-shielded skin. We conclude that, in addition to being a tumorigenic mutagen, sunlight acts as a tumor promoter by favoring the clonal expansion of p53-mutated cells. These combined actions of sunlight result in normal individuals carrying a substantial burden of keratinocytes predisposed to cancer.     

Thirty years later: Attitudes toward the employment of older workers.

Replicated W. K. Kirchner and M. D. Dunnette's (see record 1955-03161-001) study on attitudes toward older workers with 71 male and 5 female hourly employees (aged 18–61 yrs) and 22 male supervisors (aged 27–63 yrs) of a nonunion manufacturing plant. Ss completed a questionnaire that was nearly identical to the one administered in the Kirchner and Dunnette study. Results are similar to those obtained in the earlier study: Hourly workers held more positive attitudes toward older employees than did supervisors, and attitude score correlated strongly with the age of hourly workers but not with the age of supervisors. (9 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Coupled bending–torsional dynamic stiffness matrix for axially loaded beam elements

Analytical expressions for the coupled bending–torsional dynamic stiffness matrix elements of an axially loaded uniform beam element are derived in an exact sense by solving the governing differential equations of motion of the beam. The influence of axial force on the coupled bending–torsional frequencies of a cantilever and hinged–hinged beam of thin-walled section is demonstrated by numerical results. Application of the developed theory includes coupled bending–torsional frequency and mode calculations of helicopter, turbine and propeller blades, plane and space frames, and grillages consisting of axially loaded beam elements with non-coincident mass centre and shear centre.     

Nitrone spin-traps block calcium channels and induce pulmonary artery relaxation independent of free radicals

Free radicals react with nitrones to form stable nitroxides which can be identified by ESR spectroscopy. Unfortunately, little is known regarding the pharmacological properties of these compounds. In this study, three commonly used nitrones, 5,5-dimethylpyrroline-N-oxide (DMPO), alpha-phenyl-tert-butylnitrone (PBN), and alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), were found to induce relaxation of preconstricted isolated rat pulmonary artery rings. Additional experiments with PBN indicated that vasorelaxation could not be attributed to production of endothelial derived factors, prostaglandins, or free radicals. Patch-clamp techniques revealed reversible calcium channel blockade with PBN at a concentration below that needed to detect free radicals. Calcium channel blockade probably accounts for the vasorelaxation observed in the isolated ring preparations described here, and should be considered when using nitrone spin-traps both in in vivo and clinical studies.     

Finite element stress analysis of a new design of synthetic leaflet heart valve

This paper presents a parametric finite element analysis of the stresses in the leaflets of a new design of polyurethane heart valve in the closed position. The alpharabola geometry of the valve has previously been reported by Leat and Fisher (1) and has been shown to demonstrate good opening characteristics. The effects of variations in leaflet offset parameter, g, length, h, and local thickening have been determined for a valve where the frame is assumed rigid. A spherical leaflet geometry has also been analysed for comparative purposes. Results have shown that the alpharabola leaflet geometry can reduce the maximum principal tensile stress to 60 per cent of that for a spherical valve of the same mesh density.     

Apoptosis as a cause of death in measles virus-infected cells

To determine the mechanism of measles virus-induced cell death, we studied the infection of Vero cells and monocytic cell lines with wild-type (Chicago-1) and vaccine (Edmonston) strains of measles virus. DNA fragmentation indicative of apoptosis was apparent by flow cytometry, agarose gel electrophoresis, and electron microscopy. Within syncytia, DNA strand breaks were demonstrated by end labeling with terminal transferase and then by visualization.