Nuclease activity of streptococci.
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Biomedical subjects
Publications and source records attributed to R F Smith.
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A synthetic aza-cholestane amine was found to be rapidly lethal to Saccharomyces cerevisiae. Lethal action was prevented by pretreating cells with 10m uranyl nitrate. Sublethal concentrations of the steroid prevented the uptake of glucose and alanine. This demonstrated one means by which the steroid affected cell permeability, limiting the growth of the organism. Decreases in viability were related to increases in 260 and 280 mmu absorbing materials. Uranyl protection of viability was found to be related to cellular retention of the ultraviolet-absorbing materials. The steroid, dequadin acetate, and cetyl pyridinium chloride were comparable in lethal action and in causing the leakage of cytoplasmic constituents. Loss of viability and cytoplasmic excretion were detected within minutes after cells were exposed to the steroid. The rate or degree of metabolism of glucose by resting cells did not appear to influence steroid action or the sensitivity of the cells to the steroid.
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Six synthetic antimicrobial steroids were examined for indications of their mechanism of action. Dequadin acetate, cetyl pyridinium chloride (CPC), and sodium deoxycholate were studied for comparison. Aerated cells of Sarcina lutea were washed, suspended in 1.06 M sucrose, and converted to protoplasts with 20 mug/ml of lysozyme. Lysis was measured optically at 650 mmu as a decrease in optical density. Screening tests with 50 mug/ml of each compound showed five steroids and CPC to be lytic. Protoplasts were strongly protected from lysis by pretreatment with 0.001 to 0.004 M spermine tetrahydrochloride. Other polyamines, such as spermidine phosphate, were less protective, and putrescine was ineffective. Uranyl nitrate (5 x 10(-4) M) rapidly agglutinated protoplasts and protected them from rupture by the lytic agents. Similar studies with 0.001 to 0.004 M Mg(++) showed varying degrees of protection, which, in most cases, was only temporary. Steroidal lysis did not appear to be related to chelation, since ethylenediaminetetraacetate did not cause lysis alone and antagonized some lytic compounds. Lecithin, Tween 80, Tween 20, and Span 20 at 0.05% exhibited certain effects on protoplast stability. Span 20 strongly prevented lysis by steroids. Tween 20 alone quickly caused protoplast rupture. Lecithin and Tween 80, which also caused lysis alone, interfered with lytic steroids and CPC. The test compounds were both inhibitory and lethal to cells of Sarcina lutea. The results suggest that direct action on cell membranes may be chiefly responsible for the antimicrobial properties of the steroids.
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To assess the effects of prolonged space flight on the electrophysiological properties of the heart, vectorcardiograms (VCG) were obtained on the Skylab crews at regular intervals during flight and the pre- and postflight periods. The VCG signals were telemetered from Skylab and analyzed by digital computer. Conventional 12-lead electrocardiograms were derived from the VCG signals by a lead transformation program. Standardized exercise loads were incorporated into the experiment protocol to increase the sensitivity of the VCG for effects of deconditioning and to detect susceptibility for arrhythmias. In Skylab II, 24 preflight, 21 inflight, and 19 postflight experiments were analyzed. Statistically significant inflight changes observed in two or more crew members included: decreased resting heart rate, increased QRS duration, anterior shift QRS vector, increased QRS vector magnitude, anterior shift T vector, and increased T vector magnitude. One astronaut had occasional premature ventricular contractions (PVC) during the pre- and postflight phases. He had a single episode of multiple PVC's during heavy-load exercise testing in flight. A second astronaut had no arrhythmia during pre- or inflight testing. On postflight day 21 he had multiple PVC's and salvos of ectopic ventricular beats. He has had no recurrence of the arrhythmia. With the exception of the cardiac arrhythmias, no deleterious electrophysiological changes were observed during Skylab II.
Pregnant Long-Evans hooded rats were dosed via injections into the gum with 3, 6, or 9 mg/kg lidocaine, or vehicle, or were uninjected, on gestational day 4 (GD4), GD11, or GD18. Offspring (8-11 litters/group) were tested on a variety of tests of behavioral development and adult behavior. No effects of any dose at any time of administration were found upon maternal weight gain in gestation, litter size, or initial birth weight or weight gain of the pups. Administration at GD4 produced few effects; only footshock sensitivity showed a significant effect of dosing, although there were trends toward dosing effects on spontaneous alternation. For administration on GD11, lidocaine was associated with slight but significant alterations in sex ratios, and a trend toward drug effects on development of spontaneous alternation. Vehicle administration at this age reduced barbiturate sleep time in offspring and slightly altered footshock sensitivity. Lidocaine dosing on GD18 was associated with a number of significant alterations of behavior, including visual discrimination, shuttlebox avoidance, tail flick, and water maze errors; there were also both vehicle and lidocaine effects on water maze latencies. These data reinforce our previous report that lidocaine may be a behavioral teratogen, and suggest that administration in later gestation in the rat may alter a broader range of behaviors than earlier in gestation.
Pregnant Long-Evans hooded rats were dosed subcutaneously with 1 or 5 mg/kg/day naloxone hydrochloride, or an equal volume of vehicle, from gestational Day 4 (GD4) through GD19. Offspring were assessed for development of righting reflex, negative geotaxis, and open field activity, and for acquisition of a Warden maze; offspring sacrificed at postnatal Day (PND) 21 were assessed for several parameters of cerebellar, hippocampal, and motor cortical morphology. Five mg/kg/day naloxone accelerated development of negative geotaxis and righting reflex, while 1 mg/kg/day naloxone tended to slow development. Low dose females had significantly more errors than controls on the first day of maze learning. The high dose group had a significantly higher concentration of granule cells in the curvature of the dentate gyrus than controls; other neuroanatomical measures were unaffected by dosing. These findings confirm and extend previous work indicating that prenatal exposure to naloxone may alter neurobehavioral development in the rat.
Sperm-positive female Long-Evans hooded rats were dosed subcutaneously with 10 mg/kg/day cocaine or an equal volume of vehicle (0.9% sterile saline) from gestation day 4 (GD4) through GD18. Offspring were assessed for development of negative geotaxis, righting reflex, spontaneous alternation, and open field activity, and for adult behaviors including DRL-20 acquisition, water maze, visual discrimination, barbiturate sleep time, shuttlebox avoidance, footshock sensitivity, and tail flick latency. Cocaine dosing produced no significant effects on dam weight gain, any measure of litter size and weight, or early postnatal behavioral tests, but there were significant drug effects on development of spontaneous alternation, development of open field activity, DRL-20 acquisition, water maze performance, tail flick, and footshock sensitivity. These data suggest that chronic administration of a modest dose of cocaine during gestation in the rat alters a number of behaviors in the offspring.