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DE Johnson

Publications and source records attributed to DE Johnson.

10 recordsLinked to original sources
PubMed2000

Predicting human safety: screening and computational approaches.

Current preclinical safety evaluation programs use a combination of computational methods, mechanistic in vitro screening and - primarily - in vivo experimentation to predict human toxicity. The rapid transition of pharmaceutical R&D into electronic R&D (e-R&D) makes it imperative that predictive safety testing also develops into an information-rich, knowledge-based process in the near future. Accordingly, enhanced databases and computational tools are expected to change the way the pharmaceutical industry assesses drug toxicity during discovery and early development. Expert use of prediction tools should lead to lower failure rates in drug development and decrease the cost and time involved in successful drug approval.

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PubMed2000

Least-effort pathways?: a GIS analysis of livestock trails in rugged terrain.

Livestock trails frequently evolve in pastures when plant growth or establishment cannot keep pace with vegetation disturbance. In some instances, man-made trails are established in rangeland settings to encourage uniform use of forages or facilitate livestock passage through dense vegetation or across rugged terrain. A long-term assumption has been that livestock establish pathways of least resistance between frequented areas of their pastures, but this hypothesis has never been tested. We mapped cattle trails in three 800+ ha pastures with global positioning units. A geographic information system (GIS) helped quantify characteristics of trails and the landscape and was used to plot least-effort pathways between water sources and distant points on selected trails in the pastures. Characteristics of the cattle trails and least-effort pathways were compared to test the hypothesis that cattle develop least-effort routes of travel in rugged terrain. The mean slope of the three pastures was 13.5%, and the average slope of the topography traversed by the cattle trails was 8%. The slope of the trails was reduced to 5.2% by selection of cross-slope routes. When we compared the characteristics of 10 selected cattle trails and least-effort pathways generated by our GIS, the cattle trails were 11% shorter (P=0.046) than the least-effort pathways, and the topography traversed by cattle had a gradient about 1% less than the least-effort pathways (P=0.02). The slope of the selected trails (5.5%) and pathways (5.6%) were similar (P=0.74), however. Analyses of values extracted from cost surfaces indicated that, on the average, 183 units of effort were needed to traverse the trails and 170 units of effort expended to traverse the least-effort pathways (P=0.07). These data support the hypothesis that cattle establish least-effort routes between distant points in rugged terrain and suggest that GIS software may be useful in designing systems of livestock trails in extensive settings.

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PubMed1998

Spore coat protein synergizes bacillus thuringiensis crystal toxicity for the indianmeal moth

Spores from Bacillus thuringiensis serovars kurstaki and entomocidus synergized crystal protein toxicity for larvae of the Indianmeal moth (Plodia interpunctella). Preparations of spore-crystal mixtures of either serovar were more toxic for the larvae than either purified spores or crystals alone (based on dry weight). Spores lost 53% of their toxicity for the Indianmeal moth after 2 h of UV-irradiation, but remained partially toxic (28%) even after 4 h of irradiation. Spore coat protein was toxic for the Indianmeal moth and was synergistic with B. thuringiensis serovar kurstaki HD-1 crystal protein. Enhanced toxicity of the combined spore-crystal preparation was attributed to a combination of crystal and spore coat protein, and included the effects of spore germination and resulting septicemia in the larval hemolymph. Ultraviolet irradiation of spores reduced the toxicity from septicemia but not the synergism caused by spore coat protein. The potencies of spore-crystal preparations must be carefully evaluated on the basis of contributions from all three factors.

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PubMed1998

From the Editor.

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PubMed1997

Thermal Effects In Vivo from Holmium: YAG Lasing in the Intracoronary Setting.

While the thermal effect of laser energy does ablate atheromatous plaque, thermal injury to adjacent tissue produces high rates of arterial thrombosis and spasm. Holmium:YAG lasers use a pulsed laser source to maximize photoblative effects while minimizing thermal effects. These lasers have been utilized clinically to ablate thousands of complex coronary lesions with low rates of spasm and thrombosis, suggesting that little or no thermal injury occurs with these devices. However, we have been able to detect thermal injury in patients angioscopically in coronary arteries after holmium:YAG lasing. Here we report the use of directional coronary atherectomy (DCA) to ÒbiopsyÓ arteries in patients following holmium:YAG laser treatment, allowing direct histologic examination of lased tissue. Thirty such lased DCA samples were matched for patient age, gender, target vessel, and lesion characteristics with thirty control DCA samples obtained from patients undergoing DCA without prior lasing. Blinded pathologic examination correctly identified 27/30 control samples but only 18/30 lased samples. Subsequent unblinded analysis, sometimes with recutting and restaining of tissue blocks, resulted in the detection of thermal effects in 27/30 lased samples. The thermal effects seen included edge disruption, charring, coagulation necrosis, and most commonly, vacuolization. We conclude that holmium:YAG lasing does produce detectable thermal effects in tissue in most patients. These effects can be quite subtle or can be extensive, but do not predict poor patient outcome.

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PubMed1996

Contribution of Bacillus thuringiensis Spores to Toxicity of Purified Cry Proteins Towards Indianmeal Moth Larvae

The influence of Bacillus thuringiensis subsp. kurstaki HD-1 spores upon the toxicity of purified Cry1Ab and Cry1C crystal proteins toward susceptible and BT-resistant Indianmeal moth (IMM, Plodia interpunctella) larvae was investigated. With susceptible larvae, HD-1 spores were toxic in the absence of crystal protein and highly synergistic (approximately 35- to 50-fold) with either Cry1Ab or Cry1C protein. With BT-resistant IMM larvae, HD-1 spores were synergistic with Cry1Ab and Cry1C protein in all three resistant strains examined. Synergism was highest (approximately 25- to 44-fold) in insects with primary resistance toward Cry1C (IMM larvae with resistance to B. thuringiensis subsp. aizawai or entomocidus). However, HD-1 spores also synergized either Cry1Ab or Cry1C toxicity toward larvae resistant to B. thuringiensis subsp. kurstaki at a lower level (approximately five- to sixfold). With susceptible larvae, the presence of spores reduced the time of death when combined with each of the purified Cry proteins. Without spores, the speed of intoxication and eventual death for larvae treated with Cry1C and Cry1Ab proteins was much slower than for the HD-1 preparation containing both spores and crystals together. Neither spores nor toxin dose affected the mean time of death of resistant larvae treated with either Cry1Ab or Cry1C toxins. Both Cry1Ab and Cry1C toxins appeared to reduce feeding and consequently toxin consumption.

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