Auranofin affects early events in human polymorphonuclear neutrophil activation by receptor-mediated stimuli

Auranofin, a new oral antirheumatic gold compound, in concentrations achieved therapeutically, inhibits neutrophil phagocytosis, chemotaxis, chemiluminescence, reduction of cytochrome c, and release of lysosomal enzymes. To further characterize the mechanism by which auranofin affects neutrophils, we studied the effects of auranofin on unstimulated properties and functions of neutrophils as well as on rapidly stimulated functions. When examined by electron microscopy, 4 micrograms/ml of auranofin significantly decreased the number of visualized centriole-associated microtubules in resting cells. Furthermore, auranofin inhibited neutrophil spreading on glass and caused a decrease in negative surface charge (electrophoretic mobility). In addition, auranofin inhibited several fmet-leu-phe-stimulated responses such as shape change, increases in centriole-associated microtubules, decreases in surface charge, and elicited membrane potential changes (di-O-C5(3) dye response). Auranofin (1 micrograms/ml) inhibited fmet-leu-phe-stimulated superoxide and hydrogen peroxide production by 80% (p less than 0.05), and also increased the affinity of receptors for fmet-leu-phe (from Ka 0.035 to Ka 0.48, p less than 0.001). Auranofin also affected neutrophil responses to phorbol myristic acetate (PMA). The total amount of PMA-stimulated superoxide production was suppressed by as little as 0.4 micrograms/ml of auranofin, but the lag time for activation was shortened by low concentrations of auranofin (0.5 to 1 microgram/ml). Four micrograms per milliliter of auranofin suppressed the decrease in surface charge induced by PMA. However, auranofin did not influence superoxide production elicited by the ionophore A23187. The results indicate that auranofin affects the earliest detected responses in neutrophil activation by certain receptor-mediated stimuli.     

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.     

Neutrophil-stimulating activity of staphylococci based on reactive chemiluminescence data

The neutrophil-stimulating properties of 38 S. aureus strains and 32 S. epidermidis strains were studied in the reaction of luminol-mediated chemiluminescence. All S. aureus strains and 29 S. epidermidis strains were found to possess neutrophil-stimulating activity, the mean activity index for S. aureus being significantly higher. The stimulating activity of the strains varied within a wide range (the variation coefficient was 120.0 +/- 21.9%) and did not correlate with the content of protein A in bacterial cells and the degree of their hydrophoby. The opsonization of staphylococci with normal human serum enhanced the neutrophil reaction 1.5- to 100-fold and simultaneously leveled out the chemiluminescence indices in experiments with different strains (the variation coefficient was 8.0 +/- 1.5%). The nature of the neutrophil-stimulating effect of staphylococci and its relationship to the exploratory reactions of phagocytes are discussed.     

Immunity in cryptococcosis: An overview

Cryptococcosis is an often fatal opportunistic fungal infection. Despite efforts to elucidate the role of immunity in host defense against the disease, much remains to be learned. The purpose of this brief review is to provide the reader with an overview of the history of research concerned with host immunity in cryptococcosis. Both humoral and cell-mediated studies are included. An effort has been made to present the reader with a comprehensive list of references in the hope of encouraging additional reading and research in this important area.     

Heterozygote advantage in Tay-Sachs carriers?

Chi-square analyses of new data as well as data previously reported by Myrianthopoulos have shown that grandparents of Tay-Sachs carriers die from proportionally the same causes as grandparents of noncarriers. It is unlikely that there is any advantage to being a Tay-Sachs carrier insofar as resistance to tuberculosis is concerned. Our results are further evidence to support Fraikor's claim that the high carrier frequency of the allele in Ashkenazi Jews is probably caused by a combination of founder effect, genetic drift, and differential immigration patterns.     

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.