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David L Smith

Publications and source records attributed to David L Smith.

64 records · Page 4Linked to original sources
PubMed2002

Animal antibiotic use has an early but important impact on the emergence of antibiotic resistance in human commensal bacteria.

Antibiotic use is known to promote the development of antibiotic resistance, but substantial controversy exists about the impact of agricultural antibiotic use (AAU) on the subsequent emergence of antibiotic-resistant bacteria among humans. AAU for animal growth promotion or for treatment or control of animal diseases generates reservoirs of antibiotic-resistant (AR) bacteria that contaminate animal food products. Mathematical models are an important tool for understanding the potential medical consequences of this increased exposure. We have developed a mathematical model to evaluate factors affecting the prevalence of human commensal AR bacteria that cause opportunistic infections (e.g., enterococci). Our analysis suggests that AAU hastens the appearance of AR bacteria in humans. Our model indicates that the greatest impact occurs very early in the emergence of resistance, when AR bacteria are rare, possibly below the detection limits of current surveillance methods.

Agriculture↗
PubMed2002

Predicting the spatial dynamics of rabies epidemics on heterogeneous landscapes.

Often as an epidemic spreads, the leading front is irregular, reflecting spatial variation in local transmission rates. We developed a methodology for quantifying spatial variation in rates of disease spread across heterogeneous landscapes. Based on data for epidemic raccoon rabies in Connecticut, we developed a stochastic spatial model of rabies spread through the state's 169 townships. We quantified spatial variation in transmission rates associated with human demography and key habitat features. We found that large rivers act as semipermeable barriers, leading to a 7-fold reduction in the local rates of propagation. By combining the spatial distribution of major rivers with long-distance dispersal we were able to account for the observed irregular pattern of disease spread across the state without recourse to direct assessment of host-pathogen populations.

Animals↗
PubMed2002

Extracorporeal membrane oxygenation in piglets using a polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201).

PURPOSE: The purpose of this study was to determine if the polymerized bovine hemoglobin-based oxygen-carrying solution HBOC-201 is an acceptable substitute for blood in a healthy porcine, extracorporeal membrane oxygenation (ECMO) model. METHODS: Ten piglets (15 to 25 kg) were placed on venoarterial ECMO. Four animals received blood-primed ECMO, and 6 animals received HBOC-201-primed ECMO. Hemodynamic variables, urine output, blood gas analyses, complete blood counts, and lactate levels were followed for 6 hours. Data were analyzed using a nonparametric sign test and repeated measures analysis of variance (ANOVA). RESULTS: All animals survived the 6-hour ECMO procedure. Heart rate, mean arterial pressure, urine output, and serum lactate levels were not significantly different between groups. Postpriming volume was 176 +/- 156 mL in the blood group. None of the animals in the HBOC-201 group required additional volume to maintain target flow during ECMO (P <.05). Arterial pH, pO2, and oxygen content between groups were not significantly different. Hematocrit for the HBOC-201 group was significantly (P <.05) lower than the blood group. CONCLUSIONS: HBOC-201-primed ECMO in a healthy porcine model showed similar hemodynamics and equivalent oxygen carrying capacity to blood-primed ECMO. Postpriming volume requirement was decreased significantly in the HBOC group. ECMO using HBOC-201 instead of blood appears promising and warrants further investigation.

Animals↗
PubMed2002

Hydrogen exchange-mass spectrometry: optimization of digestion conditions.

The direct linkage between folded structures of proteins and their function has increased the need for high resolution structures. In addition, there is a need for analytical methods for detecting and locating changes in the folded structures of proteins under a wide variety of conditions. The rates at which hydrogens located at peptide amide linkages undergo isotopic exchange has become the basis for an important method for detecting such structural changes. When detected by mass spectrometry, hydrogen exchange can be used to study dilute solutions of large proteins and protein complexes with very high sensitivity. To locate structural changes, labeled proteins are often digested with acid proteases to form peptides whose hydrogen/deuterium levels are determined by mass spectrometry. This approach is successful only when the protein can be digested rapidly under conditions where isotope exchange is slow. This study describes how columns packed with immobilized pepsin can be used to reduce the digestion time and to provide an effective means for separating the pepsin from the isotopically labeled fragments. These columns are part of an on-line system that facilitates both rapid digestion of low concentrations of protein and concentration of the peptides.

Chromatography, High Pressure Liquid↗
PubMed2002

The polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201) is not toxic to neural cells in culture.

BACKGROUND: Recent data suggest that a neurotoxic effect of blood or its components may contribute to secondary neural cell dysfunction. This study investigated the effects of HBOC-201 (Hemopure) and purified human hemoglobin (hHgb) on rat fetal neural cell culture. METHODS: Neural cell cultures were exposed to HBOC-201 and hHgb (0.02, 0.2, 2.0, and 6.5 g/dL) for 24 hours, and then analyzed for proliferation, metabolism, and neurolysis. RESULTS: Cultures exposed to HBOC-201 maintained levels of proliferation and metabolism similar to controls while demonstrating no cellular lysis. However, cultures exposed to hHgb demonstrated decreased proliferation after exposure to 0.2, 2.0, and 6.5 g/dL hHgb (14,252.14, 3,221.89, and 343.12 vs. 19,509.53; p< 0.05) when compared with controls. In addition, cultures exposed to hHgb demonstrated decreased metabolic activity and increased cell lysis when compared with controls (p < 0.05). CONCLUSION: Cultures exposed to HBOC-201 displayed sustained metabolic activity and proliferation, and demonstrated no neurolysis, suggesting that HBOC-201 does not display the toxic characteristics of hHgb.

Analysis of Variance↗
PubMed2002

Down-regulation of tomato beta-galactosidase 4 results in decreased fruit softening.

Transcript abundance of the gene encoding beta-galactosidase II, a beta-galactosidase/exo-galactanase (EC 3.2.1.23) present during tomato (Lycopersicon esculentum) fruit ripening, was suppressed by expression of an antisense tomato beta-galactosidase 4 (TBG4) cDNA driven by the cauliflower mosaic virus 35S promoter. RNA gel-blot analysis was used to evaluate TBG4 mRNA levels in transgenic fruit. All of the antisense lines had attenuated TBG4 mRNA levels in turning stage fruit; however, TBG4 mRNA suppression was unstable, and mRNA levels varied in red-ripe fruit among the lines. Suppression of TBG4 mRNA levels in antisense fruit was correlated with a reduction in extractable exo-galactanase activity against a lupin galactan. All of the antisense lines had reduced free galactose levels at mature green stage 4, but levels comparable with controls during ripening. Total cell wall galactosyl contents in the antisense fruit were not significantly different from control fruit. Whole-fruit firmness was measured using a texture analyzer and the means of the peak force measurements for four of six antisense lines were significantly higher than control fruit. One antisense line had red-ripe fruit that were 40% firmer than controls. Fruit from this antisense line also had the lowest TBG4 mRNA and exo-galactanase levels and the highest wall galactosyl content during the early stages of ripening, implicating an involvement of this gene product in cell wall modification leading to fruit softening.

Biomechanical Phenomena↗
PubMed2001

Jasmonate and salicylate induce the expression of pathogenesis-related-protein genes and increase resistance to chilling injury in tomato fruit.

Treatment of tomato (Lycopersicon esculentum L. cv. Beefstake) fruit with low concentrations of (0.01 mM) methyl jasmonate (MeJA) or methyl salicylate (MeSA) substantially enhanced their resistance to chilling temperature and decreased the incidence of decay during low-temperature storage. While studying the expression of pathogenesis-related (PR) protein genes, different accumulation patterns of PR-protein mRNAs in tomato fruit were observed. MeJA substantially increased the accumulation of PR-2b transcripts encoding intracellular beta-1,3-glucanase and enhanced the mRNA levels of PR-2a and PR-3b encoding extracellular beta-1,3-glucanase and intracellular chitinase, respectively. MeSA substantially increased accumulation of PR-2b and PR-3a mRNAs and slightly increased PR-3b mRNA accumulation. Chilling temperature did not appreciably enhance the accumulation of PR-protein mRNAs in untreated fruit. However, the accumulation of PR-3b mRNAs in MeSA-treated fruit was enhanced following low-temperature storage. Transcript abundance of catalase genes also was investigated in different pretreated tomatoes. The accumulation of cat1 mRNA was increased substantially by MeJA, while it was reduced by MeSA treatment. These results suggest that the pre-treatment of tomato fruit with MeSA or MeJA induces the synthesis of some stress proteins, such as PR proteins, which leads to increased chilling tolerance and resistance to pathogens, thereby decreasing the incidence of decay.

Acetates↗
PubMedDate not supplied

Morphometry of hepatic neoplasms and altered foci in the mummichog, Fundulus heteroclitus.

The goal of this study was to intensively sample a small number of livers from a population of mummichog exposed to PAH-contaminated sediments and evaluate them for lesion pathology, distribution, shape, and volume, and the number of histological sections needed to adequately describe the extent of various lesions. Volumetric data for each lesion type from each step section was derived from digitized section images. The total number of hepatic alterations ranged from 10-125 per fish. Alterations included: eosinophilic, basophilic, and clear cell foci; hepatocellular carcinomas; hemangiopericytomas; and cholangiomas. Lesion volumes ranged from 0.00012-64 mm3 and represented 0.21%-67% of total liver volume. There was a tendency for the lesions to be more dorsal-ventrally compressed than spherical or ropelike when observed from longitudinal sections. Periodic subsampling of the data indicated that. on average, 6 evenly spaced, longitudinal histological sections were required to accurately estimate lesion volume and extent in our model population. These data provide a formulation for histological sampling techniques and methodological support for piscine and other cancer study models that observe lesion volume changes over time. Further, this study fosters the development of early quantitative endpoints. rather than using a large number of animals and waiting for tumor progression or death to occur.

Animals↗
PubMedDate not supplied

Will a global subsidy of new antimalarials delay the emergence of resistance and save lives?

Artemisinin-based combination treatments (ACTs) are seen as an important tool in the global effort to roll back malaria. With parasite resistance to chloroquine increasing rapidly in many parts of the world, there is greater recognition of the need for a globally coordinated strategy to ensure that artemisinins are not used as monotherapy, which has the potential to cut short their useful therapeutic life. We find that even a partial subsidy could delay the emergence of resistance and that a delay in implementing a subsidy for ACTs could facilitate the emergence of resistance and lower the economic value of ACTs.

Animals↗