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Biomedical subjects

S Stanley

Publications and source records attributed to S Stanley.

At least 19 recordsLinked to original sources

Detection of polycyclic aromatic hydrocarbons using quartz crystal microbalances.

A chemically coated piezoelectric sensor has been developed for the determination of PAHs in the liquid phase. An organic monolayer attached to the surface of a gold electrode of a quartz crystal microbalance (QCM) via a covalent thiol-gold link complete with an ionically bound recognition element has been produced. This study has employed the PAH derivative 9-anthracene carboxylic acid which, once bound to the alkane thiol, functions as the recognition element. Binding of anthracene via pi-pi interaction has been observed as a frequency shift in the QCM with a detectability of the target analyte of 2 ppb and a response range of 0-50 ppb. The relative response of the sensor altered for different PAHs despite pi-pi interaction being the sole communication between recognition element and analyte. It is envisaged that such a sensor could be employed in the identification of key marker compounds and, as such, give an indication of total PAH flux in the environment.

Anthracenes↗

Antiapoptotic function of NF-kappaB in T lymphocytes is influenced by their differentiation status: roles of Fas, c-FLIP, and Bcl-xL.

Inducible protection from apoptosis in vivo controls the size of cell populations. An important question in this respect is how differentiation affects mechanisms of apoptosis regulation. Among mature T lymphocytes, the NF-kappaB/Rel transcription factors are coupled to receptors that control cell population sizes by concurrently regulating survival and multiplication. In the present study, we used a transgenic inhibitor of NF-kappaB/Rel signaling to investigate the role of this pathway in proliferation and death of mature T cells in vivo. The results indicate that NF-kappaB integrates two critical yet distinct molecular pathways preventing apoptosis affected by the death receptor Fas, coordinately regulating levels of FLIP and Bcl-x(L) in primary T cells. Surprisingly, NF-kappaB blockade preferentially impacted naive as compared to memory T cells. The Fas/FasL pathway was linked to these findings by evidence that the abnormalities imposed by NF-kappaB inhibition were ameliorated by Fas deficiency, particularly for the CD4(+) lineage. Moreover, levels of an inhibitor of Fas-mediated apoptosis, c-FLIP, were diminished in cells expressing the transgenic inhibitor. NF-kappaB was also linked to T cell survival in vivo by mediating induction of Bcl-x(L): restoration of Bcl-x(L) levels reversed the preferential deficit of naive T cells, differentially impacting the CD4 and CD8 subsets. These results show that promoting survival and effective multiplication are central roles for NF-kappaB in T lymphoid homeostasis in vivo, but this effect and its underlying mechanisms are influenced by the developmental state of the lymphocyte.

Animals↗

Molecular imprinted polymer coated QCM for the detection of nandrolone.

An acoustic wave sensor coated with an artificial biomimetic recognition element has been developed to selectively screen for nandrolone in the liquid phase. A highly specific covalently imprinted polymer (MIP) was spin coated onto one electrode of a quartz crystal microbalance (QCM) as a thin permeable film. Selective rebinding of the nandrolone was observed as a frequency shift in the QCM for concentrations up to 0.2 ppm with the sensor binding shown to favour nandrolone over analogous compounds.

Anabolic Agents↗

In vitro investigation of the interaction between nitric oxide and cyclo-oxygenase activity in equine ventral colon smooth muscle.

The objective of this study was to determine if a correlation exists between the presence of nitric oxide and prostaglandin release in the equine ventral colon smooth muscle, since this relationship may accentuate the inflammatory process during intestinal injury. Tissue was collected from the ventral colon, cut into muscle strips oriented along the circular, longitudinal and taenial layers, and mounted in a tissue bath system. Samples of the bath fluid were collected before, following electrical field stimulation (EFS), and following EFS in the presence of L-NAME, a nitric oxide synthase inhibitor. Muscle strips were also obtained following systemic administration of a cyclo-oxygnease inhibitor and samples were collected using the previously described protocol. Concentrations of prostaglandins were determined in the fluid samples using an ELISA. Electrical field stimulated release of nitric oxide produced a significant increase in prostaglandin production which did not occur in the presence of L-NAME. Systemic administration of flunixin meglumine reduced prostaglandin levels at all sampling periods, although a small increase was present following EFS. The results of this study support the hypothesis that there is a correlation between the release of nitric oxide and the production of prostaglandins in the smooth muscle of the large colon. This association between nitric oxide and prostaglandin may act as an important regulatory mechanism for various physiological mechanisms, such as vascular smooth muscle tone, and may contribute to amplified tissue injury when the induced forms of both enzymes are activated during an inflammatory insult. This suggests that the use and development of COX2 and iNOS inhibitors may help attenuate the inflammatory response following intestinal injury.

Animals↗

Prednisone per os is likely to have limited efficacy in horses.

Based on its efficacy for the treatment of human asthma, the corticosteroid prednisone is commonly used in horses for treatment of recurrent airway obstruction. However, recent studies have failed to show any benefit of prednisone tablets for the treatment of this condition. The purpose of this study was to determine why oral prednisone has poor efficacy for the treatment of heaves in horses. In a crossover study, 5 horses were given the following treatments: prednisone tablets, prednisone liquid, prednisolone tablets, prednisolone liquid and i.v. prednisolone sodium succinate (positive control). Blood samples were taken before drug administration and at selected time points during a 24 h period. Serum concentrations of prednisone and prednisolone were determined in order to evaluate gastrointestinal absorption and hepatic metabolism. Serum concentrations of the endogenous glucocorticoid hydrocortisone were also determined as an indicator of the biological activity of the drugs. Both prednisolone tablets and liquid were absorbed rapidly, with prednisolone detectable in serum within 15 min of administration and with peak concentrations occurring within 45 min. Small amounts of prednisone were detected in the serum samples after administration of both prednisone tablets and liquid. Prednisolone was not detected in serum samples after administration of prednisone liquid and was detected in serum samples from only one horse after administration of prednisone tablets. Endogenous hydrocortisone production was suppressed when horses received prednisolone. The results of these studies indicate that prednisone has poor efficacy for the treatment of heaves because it is poorly absorbed and the active metabolite prednisolone is rarely produced. In contrast, prednisolone tablets have excellent bioavailability and should be useful as a therapeutic agent in horses.

Administration, Oral↗

Inefficient ZAP-70 phosphorylation and decreased thymic selection in vivo result from inhibition of NF-kappaB/Rel.

Signaling from the TCR regulates T lymphoid survival, deletion by apoptosis, and selective clonal expansion. One set of signaling pathways activated during thymic selection leads to degradation of a cytosolic retention protein, the inhibitor of kappaB (IkappaB)alpha, followed by nuclear translocation of the NF-kappaB/Rel family of transcription factors. It has been found previously that NF-kappaB proteins mediate a pathway signaling the survival of mature T cells and protection of thymocytes against TNF-induced apoptosis. In contrast, we show in this study that a transgenic inhibitor of NF-kappaB/Rel signaling interferes with the negative selection of immature thymocytes by endogenous MHC ligands in vivo. Positive selection of the H-Y TCR also was diminished. This attenuation of thymic selection efficiency was associated with decreased ZAP-70 phosphorylation and TCR signaling of CD69 induction. These findings demonstrate that the NF-kappaB transcriptional pathway plays an important role in normal processes of clonal deletion and they indicate that the NF-kappaB/IkappaB axis can regulate the efficiency of TCR signaling.

Animals↗

Molecular-imprinted, polymer-coated quartz crystal microbalances for the detection of terpenes.

A piezoelectric sensor coated with an artificial biomimetic recognition element has been developed for the determination of L-menthol in the liquid phase. A highly specific noncovalently imprinted polymer (MIP) was cast in situ on to the surface of a gold-coated quartz crystal microbalance (QCM) electrode as a thin permeable film. Selective rebinding of the target analyte was observed as a frequency shift quantified by piezoelectric microgravimetry with the QCM. The detectability of L-menthol was 200 ppb with a response range of 0-1.0 ppm. The response of the MIP-QCM to a range of monoterpenes was investigated with the sensor binding menthol in favor of analogous compounds. The sensor was able to distinguish between the D- and L-enantiomers of menthol owing to the enantioselectivity of the imprinted sites. To our knowledge, this is the first report describing enantiomeric resolution within an MIP utilizing a single monomer-functional moiety interaction. It is envisaged that this technique could be employed to determine the concentration of terpenes in the atmosphere.

Journal Article↗

Disembodiment is a cyberspace myth: discourse and the self in real space.

Much social science writing about the Internet is disembodied. This paper will try show how this is rhetorically practiced by the cyberfeminist author Sadie Plant. From the work of Fred Newman, Michael Billig, and also from discourse work, comes the idea that it is not views that should be studied per se, but rather, the giving of views. To understand people, one needs to understand them when they are in dialogue with one another. Not to test them in isolation, but to study their interrelatedness as they perform social life. A social space was constructed through which embodiment could be revealed. This reality is "real space," the space that is on the other side of the screen, so to speak. To understand the psychology of the Internet is to enter into dialogue with people, and real space constitutes the embodied practice of social talk, specifically in the context of the interview. Two semistructured interviews were carried out with a student from the Ukraine. These interviews were transcribed closely. Just as real space constitutes interviews, cyberspace constitutes E-mailing. An international student born in New Zealand was questioned through E-mail. A discourse analysis was performed on selected extracts. The sequences were typified by diversity and multiplicity of theme, which included the drawing upon of embodied resources. The experience of being internationals in a U.K. academic institution were perpetually being negotiated, concomitantly to the giving of views about the Internet. The problematic issues of writing about social life are practically addressed in the discussion. I explore the realities created by real space and cyberspace by deconstructing them. Discourse work allowed for a critical self-reflection concerning the meanings that were given to the performance of the Internet.

Adult↗

Food allergens.

A number of advances in the scientific knowledge concerning adverse food reactions have been made in the past few years. Understanding about the nature of the food allergen itself, the molecular characterization of the epitopes on these allergens, the pathophysiology of the clinical reaction, and the diagnostic methods have all been significantly enhanced.

Allergens↗

Statistical evaluation of the regulatory guidelines for use of furosemide in race horses.

The pharmacokinetic behavior of furosemide concentrations in performance horses is of great interest to the equine industry and equine researchers. Specifically, such information is useful for the evaluation of the existing guidelines in several racing jurisdictions and for the possible development of new guidelines for varying time periods after administration. We studied several approaches within the framework of nonlinear mixed effects models to increase the accuracy of evaluating these guidelines. Theoretical properties of the proposed methods were examined and the variances of the resulting estimators compared. Their numerical performances were further evaluated through simulations. Finally, we applied these methods to a furosemide concentration profile data set and used our findings to address certain important practical issues.

Animals↗

In vitro effects of 5-hydroxytryptamine and cisapride on the circular smooth muscle of the jejunum of horses.

OBJECTIVE: To determine effects of cisapride and 5-hydroxytryptamine (5-HT) on the jejunum of horses. SAMPLE POPULATION: Jejunal muscle strips from 8 horses. PROCEDURE: Muscle strips were suspended in isolated muscle baths. Isometric stress responses to 5-HT and cisapride, with and without specific antagonists, were determined. RESULTS: Muscle strips incubated with atropine and tetrodotoxin responded to 5-HT and cisapride with an increase in contractile force. The 5-HT caused a concentration-dependent increase in contractile amplitude, with a maximum response (Emax) of 1,151+/-214 g/cm2 and a molar concentration that induces contractile force equal to 50% of maximum response (EC50) of 0.028+/-0.002 microM. Prior incubation with the 5-HT2 antagonist ketanserin decreased the Emax (626 +/-147 g/cm2) and potency (EC50, 0.307+/-0.105 microM) of 5-HT Prior incubation with the 5-HT3 antagonist tropisetron decreased the efficacy (Emax, 894+/-184 g/cm2) to 5-HT Cisapride also caused a concentration-dependent increase in contractile amplitude, with an Emax of 331+/-82 g/cm2 and an EC50 of 0.302+/-0.122 microM. Prior incubation with ketanserin decreased the Emax (55+/-17 g/cm2) and potency (EC50, 0.520+/-0.274 microM) of cisapride. CONCLUSION AND CLINICAL RELEVANCE: Stimulatory effects of 5-HT and cisapride on circular smooth muscle of equine jejunum are mediated primarily through a noncholinergic effect. The effects of 5-HT are mediated, at least partially, by 5-HT2 and 5-HT3 receptors, whereas the effects of cisapride are mediated primarily by 5-HT2 receptors. This may impact treatment of horses with postoperative ileus.

Animals↗

The central nervous system, its cellular organisation and development, in the tadpole larva of the ascidian Ciona intestinalis.

From its numerical composition, the central nervous system (CNS) of the ascidian larva is one of the simplest known nervous systems having a chordate plan. Fewer than 350 cells together constitute a caudal nerve cord, an interposed visceral ganglion containing motor circuits for swimming and, rostrally, an expanded sensory vesicle containing major sensory and interneuron regions of the CNS. Some cells are ependymal, with ciliated surfaces lining the neural canal, while others are clearly either sensory receptors or motoneurons, but most are distinguishable only on cytological grounds. Although reassignments between categories are still being made, there is evidence for determinancy of total cell number. We have made three-dimensional cell maps either from serial semithin sections, or from confocal image stacks of whole-mounted embryos and larvae stained with nuclear markers. Comparisons between the maps of neural tubes in embryos of successive ages, that is, between cells in one map and their progeny in older maps, enable us to follow the line of mitotic descent through successive maps, at least for the caudal neural tube. Details are clear for the lateral cell rows in the neural tube, at least until the latter contains approximately 320 cells, and somewhat for the dorsal cell row, but the ventral row is more complex. In the hatched larva, serial-EM reconstructions of the visceral ganglion reveal two ventrolateral fibre bundles at the caudalmost end, each of 10-12 axons. These tracts include at least five pairs of presumed motor axons running into the caudal nerve cord. Two pairs of axons decussate. Complementing this vertebrate feature in the CNS of the larval form of Ciona, we confirm that synapses form upon the somata and dendrites of its neurons, and that its motor tracts are ventral.

Animals↗

Absence of detectable pharmacological effects after oral administration of isoxsuprine.

Isoxsuprine is reported to be a peripheral vasodilator used in human and veterinary medicine to treat ischaemic vascular disease. In horses, it is generally administered orally to treat navicular disease and other lower limb problems. To define the scope and duration of its pharmacological responses after oral administration, 6 horses were dosed with isoxsuprine HCl (1.2 mg/kg bwt) q. 12 h for 8 days and then tested to assess the duration and extent of pharmacological actions. There was no significant difference between isoxsuprine and control treatment values for heart rate, spontaneous activity, sweat production, anal muscle tone, core and skin temperatures, and cutaneous blood flow. The lack of pharmacological effect following oral administration was in sharp contrast to the marked response following i.v. dosing reported in earlier experiments.

Administration, Oral↗

Incidence of sporting injury in New Zealand youths aged 6-15 years.

OBJECTIVE: To document the incidence of injury in 6-15 year olds playing rugby union, rugby league, and netball, and to identify the common mechanisms, sites, severity, and time of injury. METHODS: Cross sectional data were collected by trained observers who watched 258 games of rugby union, netball, and rugby league over a four week period. The condition of the injured participants was monitored until recovery. RESULTS: In total, 5174 players were observed and an injury rate of 18 per 1000 player hours was calculated. Of all observed injuries, 29% required some form of medical treatment. A significant difference (p<0.05) in the distribution of injury over the four quarters of the games was recorded, most occurring in the first three quarters. In total, 81% of the injuries were classified as contact injuries, and these mainly occurred through direct contact with the opposition. Of all observed injuries, 27% were recurrent. CONCLUSIONS: The incidence of injury in rugby union, netball, and rugby league is low for children aged between 6 and 15 years relative to adult rates.

Adolescent↗

Immunopathogenic mechanisms of HIV infection.

A complex array of multiphasic and multifactorial immunopathogenic mechanisms are involved in the establishment and progression of human immunodeficiency virus (HIV) disease. After primary infection, acute viremia occurs with wide dissemination of HIV. During this early viremic phase, the virus is trapped within the processes of follicular dendritic cells in the germinal centers of lymphoid tissue. Also, during this phase of primary infection, some patients show major expansions of certain subsets of CD8+ T cells that are identified by the expression of a particular variable region of the beta chain of the T-cell receptor. These expansions are manifestations of responses to HIV that may be important in controlling the progression of HIV infection. In addition, inappropriate immune activation and elevated secretion of certain proinflammatory cytokines occur during HIV infection; these cytokines play a role in the regulation of HIV expression in the tissues. Infection of progenitor cells in bone marrow and the thymus contribute to the lack of regeneration of immunocompetent cells. Dendritic cells are involved in the initiation and propagation of HIV infection in CD4+ T cells. In studies of long-term nonprogressors - persons who have stable CD4+ T-cell counts and no HIV disease progression despite years of HIV infection - preserved lymph node architecture, low viral burden, and viral expression were found.

Dendritic Cells↗

Quadriceps muscle training in a restricted range of motion: implications for anterior cruciate ligament deficiency.

This study examined the transferability of strength gains associated with training in a limited range of motion, and at a specific joint angular velocity, to a different part of the range of motion. Work was assessed in control (N = 14) and experimental (N = 14) groups that performed baseline tests on a Kin-Com dynamometer at 1.05, 2.09, and 3.14 rad/sec, over a range of motion from 90 degrees flexion to full extension. The experimental group then underwent training consisting of three sets of eight maximum-effort knee extensions on a Kin-Com dynamometer at a joint angular velocity of 2.09 rad/sec, three times per week for 8 weeks. The range of motion at which they trained was 90 degrees to 45 degrees. After training, baseline tests were repeated in both groups. The findings showed that the work done by the quadriceps muscles of the experimental group increased significantly (p < .05) in the training range of motion across all joint angular velocities. In the untrained range of motion, the work done by the experimental group increased significantly (p < .05) only at the training angular velocity of 2.09 rad/sec. These findings provide evidence that training in a range of motion in which anterior shear forces are low can lead to changes in strength in the range of motion in which anterior shear forces are high. Hence, such exercise is of potential benefit to the anterior cruciate ligament-deficient individual.

Adult↗

Surfactant content in children with inflammatory lung disease.

OBJECTIVE: To determine surfactant profiles of tracheal secretions in mechanically ventilated children with respiratory failure secondary to bacterial pneumonia, viral pneumonitis, adult respiratory distress syndrome (ARDS), and cardiopulmonary bypass. DESIGN: Prospective, cohort study. SETTING: Tertiary, multidisciplinary, pediatric intensive care unit. PATIENTS: One hundred twenty pediatric patients with respiratory failure requiring mechanical ventilation. INTERVENTIONS: Routine tracheal aspirates were collected from children with bacterial pneumonia, viral pneumonitis, ARDS, postcardiopulmonary bypass, and a postsurgical control group. Samples were obtained on days 1, 2, 3, after every week of intubation and on the day of extubation. MEASUREMENTS AND MAIN RESULTS: The tracheal aspirates were analyzed by high-performance liquid chromatography for lecithin/sphingomyelin rations and by enzyme-linked immunosorbent assay for surfactant proteins A and B. Lung compliance and the oxygenation index were measured on each day of sample collection. On day 1, patients with bacterial pneumonia, viral pneumonitis, and ARDS had decreased lecithin/sphingomyelin ration (p < .001), and those patients with bacterial pneumonia and viral pneumonitis had decreased surfactant protein A/protein concentration (p < .001). The lecithin/sphingomyelin ratios and surfactant protein A/protein concentration were significantly different among the groups (p < .001), with the bacterial pneumonia and viral pneumonitis groups having higher lecithin/sphingomyelin ratios and increased surfactant protein concentrations before extubation. Pulmonary compliance was lower and the oxygenation index was higher than controls (p < .001) in patients with bacterial pneumonia, viral pneumonitis, and ARDS. Pulmonary compliance was correlated weakly with lecithin/sphingomyelin ratio (r2 = .11, p < .001) and surfactant protein A/protein concentration (r2 = .03, p < .05). Surfactant protein B was similar in the diagnostic groups. Surfactant content in tracheal secretions from cardiopulmonary bypass patients was equivalent to controls. CONCLUSION: Abnormal tracheal aspirate surfactant phospholipids and surfactant protein A were noted in children with bacterial pneumonia, viral pneumonitis, and ARDS, but not in children on cardiopulmonary bypass.

Cardiopulmonary Bypass↗