Modulation of ultraviolet light mutational hotspots by cellular stress.

Stressful treatments of cells provoke broad, transient, changes in cellular physiology and gene expression. In addition to these effects, DNA-damaging agents often induce permanent change in the form of mutations. Mutational patterns in target genes typically show hotspots and coldspots, the molecular basis of which appears to lie in the sequence context of the particular site. We determined the mutational pattern in an ultraviolet light-modified (in vitro) marker gene in a shuttle vector passaged through repair deficient (xeroderma pigmentosum) cells and compared it with patterns obtained from cells exposed to stress imposed by a DNA-damaging agent or a calcium ionophore. We found that the mutational hotspot pattern was altered by both stress treatments. We conclude that the cellular environment can influence the probability of mutagenesis at specific sites and propose that some of these effects on mutagenesis are mediated by alterations in cellular calcium levels.     

Gastrointestinal pH measurement in rats: influence of the microbial flora, diet and fasting

The pH of the rat intestinal tract was decreased by the presence of a microbial flora, but its influence in the forestomach is less clear. Stomach pH values varied according to the amount of food present at the time of measurement. Fasting increased the pH of the gastrointestinal tract in conventional rats but had little effect in germfree rats. In the conventional rat, feeding a purified diet compared with a commercial diet resulted in a lower pH in the forestomach and a higher pH in the caecal contents. Magnesium trisilicate promoted gastric emptying in conventional rats and its antacid effect was observed only in the caecum and colon.     

A chronic implant for recording of cochlear potentials in primates

A new technique for the continuous recording of peripheral bioelectrical activity in the auditory system of primates is described. Because of basic differences in the anatomy of the temporal bone, the approach to the round window of the cochlea is more difficult in most primates than in lower animals. A relatively simple surgical approach, which made possible the placement of an electrode into the perilymph of the inner ear via the well-demarcated horizontal semicircular canal was therefore developed and is described in detail. The bared tip of a Teflon-coated wire was cemented into the canal opening with carboxylate cement, and the wire attached to a permanent electrical connector on the skull. Cochlear microphonic and action potentials of 50 to 100 μV amplitude were thus recorded on a continuing basis at the same time that behavioral studies of primate auditory acuity were conducted.     

Activated lymphocytes trigger lymphoblast extravasation.

Intraperitoneal stimulation of adoptively sensitized rats with bacterial antigen promotes the localization of lymphoblasts at the site of antigen deposition. Lymphoblast extravasation activity (LEA) is generated only when specifically immune donor lymphocytes and the recipients of these cells share at least on Ag-B haplotype. However, if the specificity criteria for its formation are satisfied, LEA promotes the local development of lymphoblasts of all available specificities and irrespective of their Ag-B genotype. Allogeneic lymphoblasts do not participate actively in the delayed inflammatory reaction even when they are passively recruited into exudates. The results suggest that LEA is a T cell-derived mediator that amplifies the delayed type hypersensitivity reaction by directing recently activated lymphocytes into lesions.