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Biomedical subjects

S L Davis

Publications and source records attributed to S L Davis.

At least 19 recordsLinked to original sources

Heat stress enhances arterial baroreflex control of muscle sympathetic nerve activity via increased sensitivity of burst gating, not burst area, in humans.

The relationship between muscle sympathetic nerve activity (MSNA) and diastolic blood pressure has been used to describe two sites for arterial baroreflex control of MSNA. By determining both the likelihood of occurrence for sympathetic bursts and the area of each burst for a given diastolic blood pressure, both a 'gating' and an 'area' control site has been described in normothermic humans. Assessing the effect of heat stress on these mechanisms will improve the understanding of baroreflex control of arterial blood pressure under this thermal condition. Therefore, the purpose of this study was to test the hypothesis that heat stress enhances arterial baroreflex control of burst gating and area. In 10 normotensive subjects (age, 32+/-2 years; mean+/-s.e.m.), MSNA (peroneal) was assessed using standard microneurographic techniques. Five minute periods of data were examined during normothermic and whole-body heating conditions. The burst incidence (i.e. number of sympathetic bursts per 100 cardiac cycles) and the area of each burst were determined for each cardiac cycle and were placed into 3 mmHg intervals of diastolic blood pressure. During normotheric conditions, there was a moderate, negative relationship between burst incidence and diastolic blood pressure (slope=-2.49+/-0.38; r(2)=0.73+/-0.06; mean+/-s.e.m.), while area per burst relative to diastolic blood pressure exhibited a less strong relationship (slope=-1.13+/-0.46; r(2)=0.45+/-0.09). During whole-body heating there was an increase in the slope of the relationship between burst incidence and diastolic blood pressure (slope=-4.69+/-0.44; r(2)=0.84+/-0.03) compared to normothermia (P<0.05), while the relationship between area per burst and diastolic blood pressure was unchanged (slope=-0.92+/-0.29; r(2)=0.41+/-0.08) (P=0.50). The primary finding of this investigation is that, at rest, whole-body heating enhanced arterial baroreflex control of MSNA through increased sensitivity of a 'gating' mechanism, as indicated by an increase in the slope of the relationship between burst incidence and diastolic blood pressure. This occurrence is likely to afford protection against potential decreases in arterial blood pressure in an effort to preserve orthostatic tolerance during heat stress.

Adrenergic Fibers↗

A 2.5-Mb contig constructed from Angus, Longhorn and horned Hereford DNA spanning the polled interval on bovine chromosome 1.

The polled locus has been mapped by genetic linkage analysis to the proximal region of bovine chromosome 1. As an intermediate step in our efforts to identify the polled locus and the underlying causative mutation for the polled phenotype, we have constructed a BAC-based physical map of the interval containing the polled locus. Clones containing genes and markers in the critical interval were isolated from the TAMBT (constructed from Angus and Longhorn genomic DNA) and CHORI-240 (constructed from horned Hereford genomic DNA) BAC libraries and ordered based on fingerprinting and the presence or absence of 80 STS markers. A single contig spanning 2.5 Mb was assembled. Comparison of the physical order of STSs to the corresponding region of human chromosome 21 revealed the same order of genes within the polled critical interval. This contig of overlapping BAC clones from horned and polled breeds is a useful resource for SNP discovery and characterization of positional candidate genes.

Animals↗

Exogenous nitric oxide inhibits sympathetically mediated vasoconstriction in human skin.

Two experiments were performed to identify whether nitric oxide (NO) inhibits sympathetically mediated vasoconstriction in human skin. In eight subjects increasing doses of sodium nitroprusside (SNP; 8.4 x 10(-6)-8.4 x 10(-3)m) were administered via intradermal microdialysis. At each dose of SNP, cutaneous vasoconstrictor responsiveness was assessed during a 3 min whole-body cold stress. The relative reduction in forearm cutaneous vascular conductance (CVC) during the cold stress was significantly attenuated for SNP doses greater than 8.4 x 10(-4)m (control: 63.0 +/- 4.1%, SNP 8.4 x 10(-6)m: 57.1 +/- 4.7%, SNP 8.4 x 10(-5)m: 57.0 +/- 3.6%, SNP 8.4 x 10(-4)m: 44.5 +/- 5.4% and SNP 8.4 x 10(-3)m: 28.8 +/- 7.9%). The second experiment was performed to identify whether this response was due to NO attenuating sympathetically mediated vasoconstriction or due to a non-specific effect of an elevated CVC secondary to SNP administration. In seven subjects forearm CVC during a whole-body cold stress was assessed at two sites: at a site dilated via microdialysis administration of SNP and at a site dilated with isoproterenol (ISO). CVC was not different between sites prior to (SNP: 0.42 +/- 0.11; ISO: 0.46 +/- 0.11 AU mmHg(-1) (AU, arbitrary units), P > 0.05) or following drug infusion (SNP: 1.36 +/- 0.21; ISO: 1.27 +/- 0.23 AU mmHg(-1), P > 0.05). The reduction in CVC during the subsequent cold stress was significantly less at the SNP site (38.1 +/- 6.2%) relative to the ISO site (65.0 +/- 5.5%; P= 0.007). These data suggest NO is capable of inhibiting sympathetically mediated vasoconstriction in the cutaneous vasculature.

Adrenergic beta-Agonists↗

Pharmacokinetic and pharmacodynamic issues in the treatment of bacterial infectious diseases.

This review outlines some of the many factors a clinician must consider when selecting an antimicrobial dosing regimen for the treatment of infection. Integration of the principles of antimicrobial pharmacology and the pharmacokinetic parameters of an individual patient provides the most comprehensive assessment of the interactions between pathogen, host, and antibiotic. For each class of agent, appreciation of the different approaches to maximize microbial killing will allow for optimal clinical efficacy and reduction in risk of development of resistance while avoiding excessive exposure and minimizing risk of toxicity. Disease states with special considerations for antimicrobial use are reviewed, as are situations in which pathophysiologic changes may alter the pharmacokinetic handling of antimicrobial agents.

Anti-Bacterial Agents↗

Defining a middle ground for philosophers and production: bioethics.

From the perspective of most animal scientists and producers, animal agriculture has become increasingly contentious over the last 10 to 20 years. Furthermore, our critics seem to be extremists whose views are biased and unreasonable. But guess what? The critics say the same thing about animal producers and scientists (us). So where is the middle ground and how do we get there? Should we even worry about trying to define the middle ground? Are these contentious issues a fad that will go away? Are these "extremist" critics so far outside reason that they will be ignored by society? Ignoring "them" is not likely to work because we have seen society changing its mind (developing a new social ethic) with regard to farm animals, in part because of what these critics are saying. As a result, it is vitally important for us to know and understand what is happening and why. For example, there isn't just one voice among the critics. There is actually a spectrum of opinion among the group which conventional agriculturalists usually call their critics. The WCC-204 committee generally agrees that the key to finding the middle ground between what is perceived as a polarized set of issues between "us" (animal scientists and producers) and "them" (philosopher critics) is for both sides to learn about the reasons why each side says what they do. Only then can all parties rationally begin to identify where the middle ground lies.

Agriculture↗

Total mercury concentrations in lakes and fish of western Maryland, USA.

The purpose of this study was to quantify total mercury concentrations in three species of fish in three lakes of western Maryland: Piney Creek reservoir, Deep Creek Lake, and Lake Habeeb. We measured total mercury concentrations in water from each lake and muscle tissue from 119 fish collected in fall 2000: 15 largemouth bass (Micropterus salmoides), 15 yellow perch (Perca flavescens), and 15 bluegill (Lepomis macrochirus) from the Piney Creek reservoir; 15 largemouth bass, 15 yellow perch, and 14 bluegill from Deep Creek Lake; and 15 largemouth bass and 15 bluegill from Lake Habeeb. Average total mercury concentrations (+/- SD) in surface waters were 0.96 +/- 0.03 ng L(-1) for the Piney Creek reservoir, 0.56 +/- 0.07 ng L(-1) for Deep Creek Lake, and 0.40 +/- 0.05 ng L(-1) for Lake Habeeb. These water quality differences were sometimes reflected in the total mercury concentration in fish muscle tissue. Total mercury concentrations in bluegill (0.05 +/- 0.02 microg g(-1)) and largemouth bass (0.10 +/- 0.03 microg g(-1)) from Lake Habeeb were significantly (p < 0.001) lower than the total mercury concentrations in bluegill and largemouth bass from the Piney Creek reservoir (bluegill: 0.13 +/- 0.04 microg g(-1) and largemouth bass: 0.37 +/- 0.18 microg g(-1)) and Deep Creek Lake (bluegill: 0.11 +/- 0.04 microg g(-1) and largemouth bass: 0.30 +/- 0.09 microg g(-1)). Yellow perch from the Piney Creek reservoir had significantly higher total mercury concentrations than yellow perch from Deep Creek Lake (0.20 +/- 0.08 microg g(-1) versus 0.13 +/- 0.04 microg g(-1)). In contrast, total mercury concentrations in largemouth bass from the Piney Creek reservoir and Deep Creek Lake were not significantly different. With the exception of largemouth bass from Lake Habeeb and yellow perch from Deep Creek Lake, there were relatively strong (r(2) > 0.39-0.79) log-log relationships between the size (weight and length) of the fish and total mercury concentrations in muscle tissue. The largest largemouth bass (> 800 g and > 38 cm) from both Deep Creek Lake and the Piney Creek reservoir had total mercury concentrations that exceeded the consumption advisory of 0.5 microg g(-1) that is used by many states and Canada. In contrast, total mercury concentrations in largemouth bass from Lake Habeeb did not exceed this consumption advisory. Our results suggest that fish consumption advisories are needed for largemouth bass in the Piney Creek reservoir and Deep Creek Lake.

Animals↗

SdrG, a fibrinogen-binding bacterial adhesin of the microbial surface components recognizing adhesive matrix molecules subfamily from Staphylococcus epidermidis, targets the thrombin cleavage site in the Bbeta chain.

Staphylococcus epidermidis is an important opportunistic pathogen and is a major cause of foreign body infections. We have characterized the ligand binding activity of SdrG, a fibrinogen-binding microbial surface component recognizing adhesive matrix molecules from S. epidermidis. Western ligand blot analysis showed that a recombinant form of the N-terminal A region of SdrG bound to the native Bbeta chain of fibrinogen (Fg) and to a recombinant form of the Bbeta chain expressed in Escherichia coli. By analyzing recombinant truncates and synthetic peptide mimetics of the Fg Bbeta chain, the binding site for SdrG was localized to residues 6-20 of this polypeptide. Recombinant SdrG bound to a synthetic 25-amino acid peptide (beta1-25) representing the N terminus of the Fg Bbeta chain with a KD of 1.4 x 10(-7) m as determined by fluorescence polarization experiments. This was similar to the apparent K(D) (0.9 x 10(-7) m) calculated from an enzyme-linked immunosorbent assay where SdrG bound immobilized Fg in a concentration-dependent manner. SdrG could recognize fibrinopeptide B (residues 1-14), but with a substantially lower affinity than that observed for SdrG binding to synthetic peptides beta1-25 and beta6-20. However, SdrG does not bind to thrombin-digested Fg. Thus, SdrG appears to target the thrombin cleavage site in the Fg Bbeta chain. In fact, SdrG was found to inhibit thrombin-induced fibrinogen clotting by interfering with fibrinopeptide B release.

Adhesins, Bacterial↗

Effects of past abuse experiences on children's eyewitness memory.

Relations between child maltreatment and children's eyewitness memory were examined. A matched sample of abused and nonabused 3- to 10-year-old children (n = 70) participated in a play session with an unfamiliar adult and were interviewed about the interaction 2 weeks later. Consistent with results from previous research, older compared to younger children's reports were more complete and accurate. Abused and nonabused children performed similarly with several exceptions: Nonabused children were more accurate in answering specific questions, made fewer errors in identifying the unfamiliar adult in a photo identification task, and (at least for younger boys) freely recalled more information. Most effects remained when group differences in IQ and behavioral symptomology were statistically controlled. Importantly, abused and nonabused children did not differ in their accuracy or suggestibility in response to questions that were relevant to abusive actions. Among abused children, however, those who suffered more severe sexual abuse made more omission errors to specific abuse-relevant questions. Contributions to psychological theory and legal implications for understanding children's eyewitness memory and testimony are discussed.

Age Factors↗

Antioxidant status and oxidative stress in elite alpine ski racers.

The goal of this study was to access antioxidant status and markers of oxidative damage in elite alpine ski racers during routine training. Subjects included 12 members of the U.S. Men's Alpine Ski Team attending a 10-day summer training camp. Blood draws were collected at rest and after exercise: (a) prior to training, (b) following 2 days of dry land training, and (c) after 4 days of on-snow skiing. Seven measures of antioxidant status were determined using colorimetric and HPLC methods (Trolox equivalent antioxidant capacity, uric oxidase, alpha-tocopherol, total glutathione, cytosolic glutathione peroxidase, and superoxide dismutase). Oxidative stress was assessed using 2 markers of lipid oxidation (malondialdehyde and lipid hydroperoxides) and 2 markers of protein oxidation (carbonylated total proteins and carbonylated hemoglobin). The results of this study suggest that antioxidant status of elite alpine skiers may decline over a period of intense training. However, elevations in markers of oxidative stress were not evident.

Adult↗

Formulation of poly(D,L-lactic-co-glycolic acid) microparticles for rapid plasmid DNA delivery.

An optimised water-in-oil-in-water double emulsion process for the microencapsulation of plasmid DNA in poly(D,L-lactic-co-glycolic acid) (PLGA) was used to prepare microparticles from a range of different PLGA formulations. This process has been developed using pharmaceutically accepted solvents and is potentially scaleable. Incorporation of plasmid DNA in the microparticles of up to 11 microg/mg was obtained and the retention of plasmid DNA integrity was considerably greater than previously reported. Microparticle structure was determined, by scanning electron microscopy, to be hollow and size distribution characteristics were found to be independent of polymer formulation. The ability to vary the plasmid DNA release profile by changing the PLGA formulation and polymer concentration used in the encapsulation process was also demonstrated. This ability to control the release profile of the microparticles was shown to be especially important as the physical integrity of the encapsulated plasmid DNA was found to deteriorate with extended release times in vitro.

DNA↗

Multiple isoforms of porcine aromatase are encoded by three distinct genes.

Cytochrome P450 aromatase, a product of the CYP 19 gene and the terminal enzyme in the estrogen biosynthetic pathway, is synthesized by the ovary, endometrium, placenta, and peri-implantation embryos in the pig and other mammals, albeit to varying levels, implying its functional role(s) in pregnancy events. The aromatase produced by the pig tissues exists as three distinct isoforms (type I - ovary, type II - placenta, and type III - embryo), with presumed differences in substrate specificities, expression levels, activity, and mode of regulation. In order to delineate the molecular mechanisms whereby estrogen synthesis is regulated in these diverse tissues, the present study examined if these aromatase isoforms represent products of multiple genes or of a single gene via complex splicing mechanisms. Porcine genomic DNA from a single animal was used as a template in the polymerase chain reaction (PCR) to amplify isoform-specific sequences corresponding to exons 4 and 7, respectively. Nucleotide sequence analysis of the generated fragments revealed the presence of only clones corresponding to the three known aromatase types. Screening a porcine Bacterial Artificial Chromosome (BAC) library for aromatase gene by PCR yielded a single clone approximately 80 kb in length. Southern blot analysis, using probes specific for exons 1A-1B, 2-3, 4-9, and 10 sequences indicated that the BAC genomic clone contains the entirety of the coding exons as well as the proximal promoter region. Sequence analysis of the fragment generated with exon 4 primers determined that this BAC clone contains only the type II gene. The presence and relative orientation of the untranslated 5'- exons 1A and 1B, previously demonstrated for the type III isoform were evaluated in the BAC clone and genomic DNA by PCR. The 265 bp fragment generated from both PCR reactions was confirmed by sequence analysis to contain exons 1A and 1B that are located contiguous to each other and separated by only three bp. A diagnostic procedure for typing aromatase isoforms was developed, based on the presence of specific restriction sites within isoform-specific exons. The use of this protocol confirmed the existence of only three aromatase isoforms in the porcine genome and indicated changes in aromatase types expressed by the uterine endometrium as a function of pregnancy stage. The presence of distinct genes encoding each of the aromatase isoform predicts important differences in the mechanisms underlying the molecular evolution and regulation of porcine aromatase, unique from those of other mammals, and suggests a critical role for P450 aromatase steroidal products in uterine functions related to pregnancy events.

Animals↗

Effect of precooling on physical performance in multiple sclerosis.

Many individuals with MS experience heat sensitivity that may be associated with transient increases in the frequency of clinical signs and symptoms. Although physical activity may be beneficial for those with MS, induced thermal loads may preclude participation in exercise and other daily activities. This project was designed to evaluate the effects of precooling on physical function. Six thermosensitive MS patients were studied. Participants performed a graded exercise test to determine maximal oxygen uptake (VO2max) on a combined arm-leg ergometer. Thermal load was induced by 30 min of exercise under noncooled and precooled conditions at a workrate corresponding to 60% VO2max. Precooling consisted of 30 min lower body immersion in 16 - 17 degrees C water. Fatigue and 25-ft walk performance were assessed before, immediately after, and 30 min following exercise. No treatment differences in VO2 were observed. Rectal temperature, heart rate, and rating of perceived exertion (RPE) were significantly lower during the precooled exercise trial compared to the noncooled trial. Immediately following exercise, 25-ft walk performance and fatigue scores showed significantly greater deterioration in the noncooled condition. Precooling was effective in preventing gains in core temperature with physical work and may allow heat-sensitive individuals with MS to exercise with greater physical comfort.

Adult↗

Neonatal micrognathia is associated with small upper airways on radiographic measurement.

In order to determine if infants with clinical micrognathia identified in the newborn period have smaller upper airways than do normal infants, and if their airway size is related to risk of later apnoea, respiration-timed upper airway radiographic measurements were performed in 21 asymptomatic neonates with clinical micrognathia. Their radiographic measurements were compared with those of a previously reported cohort of 35 normal infants. The micrognathic infants and a control group of 27 infants referred for parental anxiety were followed for 6 mo on home apnoea monitors. Sleep apnoea at home requiring stimulation by the parents occurred in 6 of 7 infants with micrognathia associated with craniofacial anomalies, 9 of 14 (64%) infants with isolated micrognathia, but only 1 of the 27 control infants (p < 0.001). Upper airway measurements at term of the infants with isolated micrognathia who later experienced apnoea were significantly smaller than either those of normal infants (p < 0.01) or of micrognathic infants who did not have apnoea requiring stimulation (p < 0.05). In conclusion, upper airway measurements on timed lateral radiographs in asymptomatic micrognathic infants at term (corrected age) revealed them to be smaller than those of normal infants. Narrower upper airways were associated with increased risk of subsequent apnoea requiring stimulation.

Apnea↗

Organophosphorus-induced neurotoxicity in the absence of neuropathy target esterase inhibition: the effects of triphenyl phosphine in the European ferret.

Abou-Donia et al. (in Toxicologist, Vol. 30, 1996) have reported that repeated oral administration of the organo-phosphorus compound triphenyl phosphine (TPPn) to the domestic chicken results in neuropathological changes in the spinal cord and peripheral nerves, accompanied by ataxia and paralysis. This study also noted that single doses of TPPn resulted in no inhibition of the enzymes neuropathy target esterase (NTE) and acetylcholinesterase (AChE). We undertook the present study to determine the biochemical, neuropathological, and clinical effects of single doses of TPPn in the European ferret, a mammalian species shown to be susceptible to organophosphorus-induced neurotoxicity. Eight 12-week-old ferrets were each injected subcutaneously with either 250 mg TPPn/kg bw or 500 mg TPPn/kg bw, or with the peanut oil/ethyl ether vehicle. Twenty-four h after dosing, the brains of 5 animals from each dose group were examined for NTE and AChE activities. The remaining 3 animals in each group were observed for 6 days for the development of clinical signs, after which their brains were processed for the presence of axonal degeneration using the Fink-Heimer silver impregnation method. Single injections of TPPn had no effect on the activities of whole-brain NTE or AChE 24 h after injection. The animals observed for clinical signs showed increasing trunk and hindlimb ataxia beginning 4 days after injection, culminating in fore-and hindlimb paralysis 6 days after injection. All brains exposed to either dose of TPPn showed widespread axonal degeneration extending from the brainstem and cerebellum into midbrain and forebrain areas. The results of this study support the hypothesis that TPPn-induced neurotoxicity is a separate and distinct form of organophosphorus-induced neurotoxicity not dependent on NTE inhibition, and therefore not a variant of organophosphorus-induced delayed neurotoxicity (OPIDN).

Acetylcholinesterase↗

Role of the cerebrovascular and metabolic responses in the delayed phases of injury after transient cerebral ischemia in fetal sheep.

BACKGROUND AND PURPOSE: Perinatal hypoxic-ischemic injuries can trigger a cascade of events leading to delayed deterioration and cell death several hours later. The objective of this study was to characterize the cerebral blood flow responses and the changes in extracellular glucose and lactate during the delayed phases of injury and to determine their relationships with the pathophysiological events after hypoxic-ischemic injury. METHODS: Two groups of near-term chronically instrumented fetal sheep were subjected to 30 minutes of cerebral hypoperfusion. In the first group, regional cerebral blood flow was measured over the next 24 hours with radiolabeled microspheres. In the second, cortical extracellular glucose and lactate were measured by microdialysis. Parietal electrocorticographic activity and cortical impedance were recorded continuously in both groups, and the extent of neuronal loss was determined histologically at 72 hours after injury. RESULTS: Cerebral blood flow was transiently impaired in the cortex during reperfusion, whereas during the delayed phase, there was a marked increase in cerebral blood flow. The severity of cortical neuronal loss was related to the degree of hypoperfusion in the immediate reperfusion period and inversely related to the magnitude of the delayed hyperperfusion. Cortical extracellular lactate was elevated after injury, and both glucose and lactate secondarily increased during the delayed phase of injury. CONCLUSIONS: The delayed phase is accompanied by a period of hyperperfusion that may protect marginally viable tissue.

Animals↗

Team approach to teaching participatory group process involving natural resources and agriculture.

Contemporary issues are defined by people who share diverse and often strongly defended views about the topic. In Oregon, citizens are increasingly being asked or expected to participate in complex decisions that require a consensus. Rather than teach one professor's synthesis of a contemporary natural resource issue, faculty from six disciplines coach group process, interactive learning skills, and systems thinking as a way to address complex issues from multiple perspectives. Students learn by grappling with a natural resource issue of their choice within groups based on a diversity among majors, degree status, and gender. Students define situation (S), brainstorm new or different targets (T), and analyze two or more pathways (P), using an STP learning and action process. Exploring potential pathways involves defining possible consequences, stakeholder views, feasibility (ecological, social, economic, and political), and planning that includes expected behavior of the improved system over time. Students present their topics and improvements showing systemic relationships, systematic analysis, and integration of scientific facts and secondary data at midterm and during finals. Reflective learning is fostered throughout the course with prompted questions in a journal notebook. Grading criteria promote meaningful inquiry and participation in group process combined with integration of scientific facts and reflective learning.

Agriculture↗