Biomedical subjects

A C Johnson

Publications and source records attributed to A C Johnson.

At least 19 recordsLinked to original sources

PubMed2006

A practical demonstration in modelling diclofenac and propranolol river water concentrations using a GIS hydrology model in a rural UK catchment.

An existing GIS hydrology water quality model, LF2000-WQX, was applied to predict the concentrations of the pharmaceuticals diclofenac and propranalol in catchments. As a practical exercise the predominantly rural Tamar (UK) catchment was chosen. Consumption, excretion, and fate data were used to estimate the pharmaceutical input load for the model. The predicted concentrations throughout most of the catchment were 1 ng/L or less under low flow (90th percentile) conditions. However, at a few locations, downstream of small sewage treatment plants, concentrations above 25 ng/L were predicted. This exercise shows that it is relatively straightforward to predict the concentrations of new and emerging organic microcontaminants in real catchments using existing GIS hydrology water quality models. Further testing will be required to establish their accuracy.

Computer Simulation↗

PubMed2006

Effect of exchange interaction on spin dephasing in a double quantum dot.

We measure singlet-triplet dephasing in a two-electron double quantum dot in the presence of an exchange interaction which can be electrically tuned from much smaller to much larger than the hyperfine energy. Saturation of dephasing and damped oscillations of the spin correlator as a function of time are observed when the two interaction strengths are comparable. Both features of the data are compared with predictions from a quasistatic model of the hyperfine field.

Journal Article↗

PubMed2006

Contamination of headwater streams in the United Kingdom by oestrogenic hormones from livestock farms.

Most studies of hormonal activity in rivers have focused on inputs from sewage treatment works (STW), and their consequences for endocrine disruption in fish. It is possible that livestock is contributing to this hormonal activity in rivers. This study represents a search for evidence of steroid hormone contamination in streams associated with livestock farms. The majority of the 10 sites selected were streams running through dairy farms, although some examples of beef, sheep and pigs were included. Passive water samplers (Polar Organic Chemical Integrative Samplers-POCIS) were deployed up- (control) and down-stream of the farms for 3 to 10 weeks (mean=39 days) during the period November 2004 to January 2005. At one site, water samples were also taken automatically during rainfall events. All samples were solvent-extracted. Total oestrogenic activity in concentrates of the extracts was analysed using the Yeast Estrogen Screen (YES) calibrated against 17beta-oestradiol (E2), while oestrone (E1), E2 and 17alpha-ethinylestradiol (EE2) were analysed by liquid chromatography-mass spectrometry (LC-MS/MS). Stream water from the entirety of only one rainfall event was sampled directly, but this revealed background activity (E2 equivalents) of 0-0.3 ng/l, rising to a transient peak of 9.4 ng/l. Average oestrogenic activity at this site as estimated from the POCIS samplers was 1.8-2.7 ng E2 equiv./l. Estimated average oestrogenic activity across all sites (with one exception) lay in the range 0-26.5 ng E2 equiv./l (mean=2.0 ng/l; S.D.=5.1), based on the POCIS samples. The outlier was 292 ng/l, and this could not be specifically linked with livestock rearing. 92% of monitoring stations (at least one on each farm) contained some oestrogenic activity, and activity was higher at downstream sites in 50% of cases. Although no EE2 was detected analytically in any stream, E1 and E2 were almost ubiquitous, with E2 equivalents ranging from 0.04 to 3.6 ng/l across all sites. Furthermore, steroid concentrations downstream of livestock were higher than upstream in 60% of cases, more markedly so than for the YES data. In several cases, activity upstream was greater than downstream, and this tended to be associated with higher activity than could be accounted for by the hormone analyses. Both the YES and chemical analytical data suggest that fish in headwater streams on or near some livestock farms may be at risk of endocrine disruption.

Chromatography, Liquid↗

PubMed2006

Validation of the proposed International Society for Heart and Lung Transplantation grading system for primary graft dysfunction after lung transplantation.

BACKGROUND: A scoring system was recently proposed to grade the severity of primary graft dysfunction (PGD), a frequent early complication of lung transplantation. The purposes of this study are to: (1) validate the PGD grading system with respect to patient outcomes; and (2) compare the performance of criteria employing the arterial oxygenation to fraction of inspired oxygen (P/F) ratio to an alternative grading system employing the oxygenation index (OI). METHODS: We retrospectively reviewed the medical records of 402 patients having undergone lung transplantation at our institution from 1992 through 2004. The ISHLT PGD grading system was modified and grades were assigned up to 48 hours post-transplantation as follows: Grade 1 PGD, P/F > 300; Grade 2, P/F 200 to 300; and Grade 3, P/F < 200. A worst score T(0-48) was also assigned, which reflects the highest grade recorded between T0 and T48. RESULTS: The prevalence of severe PGD (P/F Grade 3) declined after transplant, from 25% at T0 to 15% at T48. Grouping patients by P/F grade at T48 demonstrated the clearest differentiation of 90-day death rates (Grade 1, 7%; Grade 2, 12%; Grade 3, 33%) (p = 0.0001). T48 OI grade also differentiates 90-day death rates. There was no difference in longer-term survival between patients with PGD Grades 1 and 2. OI grade at T0 qualitatively improved differential mortality between Grades 1 and 2; however, the differences did not reach statistical significance. Patients with a worst score T(0-48) of Grade 3 PGD did have significantly decreased long-term survival, as well as longer ICU and hospital stay, when compared with Grades 1 and 2 PGD. Significant risk factors for short- and long-term mortality in our multivariate model were P/F Grade 3 [worst score T(0-48) as well as T0 grade], single-lung transplant, use of cardiopulmonary bypass and high pre-operative mean pulmonary artery pressure. CONCLUSIONS: There is an increased risk of short- and long-term mortality and length of hospital stay associated with severe (Grade 3) PGD. The proposed ISHLT grading system can rapidly identify patients with poor outcomes who may benefit from early, aggressive treatment. Refinement of the scoring system may further improve patient risk stratification.

Adolescent↗

PubMed2006

Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1.

High expression of epidermal growth factor receptor (EGFR) is found in a variety of solid tumors, including colorectal cancer. EGFR has been identified as a rational target for anticancer therapy. Curcumin, the yellow pigment of turmeric in curry, has received attention as a promising dietary supplement for cancer prevention and treatment. We recently reported that curcumin inhibited the growth of human colon cancer-derived Moser cells by suppressing gene expression of cyclinD1 and EGFR. The aim of the present study was to explore the molecular mechanisms underlying curcumin inhibition of gene expression of EGFR in colon cancer cells. The generality of the inhibitory effect of curcumin on gene expression of EGFR was verified in other human colon cancer-derived cell lines, including Caco-2 and HT-29 cells. Promoter deletion assays and site-directed mutageneses identified a binding site for the transcription factor early growth response-1 (Egr-1) in egfr promoter as a putative curcumin response element in regulating the promoter activity of the gene in Moser cells. Electrophoretic mobility shift assays demonstrated that curcumin significantly reduced the DNA-binding activity of the transcription factor Egr-1 to the curcumin response element. In addition, curcumin reduced the trans-activation activity of Egr-1 by suppressing egr-1 gene expression, which required interruption of the ERK signal pathway and reduction of the level of phosphorylation of Elk-1 and its activity. Taken together, our results demonstrated that curcumin inhibited human colon cancer cell growth by suppressing gene expression of EGFR through reducing the trans-activation activity of Egr-1. These results provided novel insights into the mechanisms of curcumin inhibition of colon cancer cell growth and potential therapeutic strategies for treatment of colon cancer.

Antineoplastic Agents↗

PubMed2006

5-HT2B receptors do not modulate sensitivity to colonic distension in rats with acute colorectal hypersensitivity.

The 5-HT4 receptor agonist tegaserod is an effective prokinetic agent that increases gastrointestinal secretion and reduces visceral sensitivity. Tegaserod has both 5-HT4 receptor agonist and 5-HT2B receptor antagonist activity, the latter being a less potent effect of the drug. In a rat model of colonic hypersensitivity, selective 5-HT4 receptor antagonists only partially reversed the antihyperalgesic effect of tegaserod suggesting that non-5-HT4 receptor-mediated mechanisms may also be involved in its overall antihyperalgesic action. The objective of this study was to determine whether 5-HT2B receptors play a role in colonic hypersensitivity. A visceromotor response (VMR) in acutely sensitized animals (intracolonic acetic acid, 0.6%, 1.5 mL) quantified colonic hypersensitivity. Acetic acid produced an increase in the VMR at all distension pressures. However, neither the 5-HT2B receptor agonist BW 723C86, the 5-HT2B antagonist SB204741 or the 5-HT2B/2C antagonist SB 206553 caused any significant inhibition of the VMR. In summary, in the same rodent model in which tegaserod has previously been shown to produce a potent antihyperalgesic effect, 5-HT2B receptors do not appear to mediate colonic hypersensitivity. We conclude that 5-HT2B receptor-mediated mechanisms are unlikely to play a role in the antihyperalgesic action of tegaserod in man.

Animals↗

PubMed2006

Effects of serotonin transporter inhibition on gastrointestinal motility and colonic sensitivity in the mouse.

Serotonin-selective reuptake transporter (SERT) expression is decreased in animal models of intestinal inflammation and in individuals with inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS), and it is possible that resultant changes in intestinal serotonin signalling contribute to the manifestation of clinical features associated with these disorders. The objective of this investigation was to determine whether inhibition of SERT function leads to changes in gut motility and sensitivity. Mice underwent a 14-day treatment with the SERT inhibitor, paroxetine (20 mg kg(-1)), or vehicle (saline/propylene glycol). Gastrointestinal (GI) transit following charcoal gavage, colonic motility, stool frequency and visceromotor responses to colorectal distension were evaluated. In mice treated with paroxetine, stool output was decreased, upper GI transit was delayed, and colonic sensitivity to a nociceptive stimulus was attenuated. These results demonstrate that reduced SERT function (via pharmacological blockade) significantly alters GI motility and sensitivity in mice, and support the concept that altered SERT expression and function could contribute to symptoms associated with IBS and IBD.

Animals↗

PubMed2005

Coherent manipulation of coupled electron spins in semiconductor quantum dots.

We demonstrated coherent control of a quantum two-level system based on two-electron spin states in a double quantum dot, allowing state preparation, coherent manipulation, and projective readout. These techniques are based on rapid electrical control of the exchange interaction. Separating and later recombining a singlet spin state provided a measurement of the spin dephasing time, T2*, of approximately 10 nanoseconds, limited by hyperfine interactions with the gallium arsenide host nuclei. Rabi oscillations of two-electron spin states were demonstrated, and spin-echo pulse sequences were used to suppress hyperfine-induced dephasing. Using these quantum control techniques, a coherence time for two-electron spin states exceeding 1 microsecond was observed.

Journal Article↗

PubMed2005

The potential steroid hormone contribution of farm animals to freshwaters, the United Kingdom as a case study.

The combined farm animal population is considerably larger than the human one in the United Kingdom, implying a possibly important contribution to the environmental load of steroid hormones entering water. To make comparisons on the amount of steroid hormones produced by the different livestock, information was gathered on the structure of the UK farm animal populations and the amount of hormones excreted by animals at each of their life stages. An individual normalised dairy cow excretes two orders of magnitude more, and a normalised pig excretes more than one order of magnitude more steroid oestrogens than a normalised human. In terms of excretion, the combined farm animal population (including sheep and poultry) probably generates around four times more oestrogens than the human population in the UK. The biggest contributor on the animal side is the relatively small dairy cow population. If steroid oestrogens behave like herbicides, in which a worst case loss to surface waters is around 1%, then it could be argued that farm animals are responsible for 15% of all the oestrogens in UK waters. When simulations were made with the MACRO pesticide leaching model, predicted concentrations for field drains failed to exceed 1 ng/L. The rapid biodegradation rates, and high sorption rates taken from the literature and used in the model suggested less than 0.001% of oestrogens would reach the field drains. This survey suggests that direct excretion of steroid hormones by animals into water courses, or discharges from farmyard drains, are likely to be more important sources of contamination rather than via normal agricultural scenarios.

Animals↗

PubMed2005

Triplet-singlet spin relaxation via nuclei in a double quantum dot.

The spin of a confined electron, when oriented originally in some direction, will lose memory of that orientation after some time. Physical mechanisms leading to this relaxation of spin memory typically involve either coupling of the electron spin to its orbital motion or to nuclear spins. Relaxation of confined electron spin has been previously measured only for Zeeman or exchange split spin states, where spin-orbit effects dominate relaxation; spin flips due to nuclei have been observed in optical spectroscopy studies. Using an isolated GaAs double quantum dot defined by electrostatic gates and direct time domain measurements, we investigate in detail spin relaxation for arbitrary splitting of spin states. Here we show that electron spin flips are dominated by nuclear interactions and are slowed by several orders of magnitude when a magnetic field of a few millitesla is applied. These results have significant implications for spin-based information processing.

Journal Article↗

PubMed2005

Comparing steroid estrogen, and nonylphenol content across a range of European sewage plants with different treatment and management practices.

The effluent of 17 sewage treatment works (STW) across Norway, Sweden, Finland, The Netherlands, Belgium, Germany, France and Switzerland was studied for the presence of estradiol (E2), estrone (E1), ethinylestradiol (EE2) and nonylphenol (NP). Treatment processes included primary and chemical treatment only, submerged aerated filter, oxidation ditch, activated sludge (AS) and combined trickling filter with activated sludge. The effluent strength ranged between 87 and 846 L/PE (population equivalent), the total hydraulic retention time (HRT) ranged between 4 and 120 h, sludge retention time (SRT) between 3 and 30 d, and water temperature ranged from 12 to 21 degrees C. The highest estrogen values were detected in the effluent of the STW which only used primary treatment (13 ng/L E2 and 35 ng/L E1) and on one occasion in one of the STW using the AS system (6.5 ng/L E2, 50.5 ng/L E1, but on three other occasions the concentrations in this STW were at least a factor of 6 lower). For the 16 STW employing secondary treatment E2 was only detected in the effluent of six works during the study period (average 0.7-5.7 ng/L). E1 was detected in the effluent of 13 of the same STW. The median value for E1 for the 16 STW with secondary treatment was 3.0 ng/L. EE2 was only detected in two STW (1.1, <0.8-2.8 ng/L). NP could be detected in the effluent of all 14 STW where this measurement was attempted, with a median of 0.31 microg/L and values ranging from 0.05 to 1.31 microg/L. A comparison of removal performance for E1 was carried out following prediction of the probable influent concentration. A weak but significant (alpha<5%) correlation between E1 removal and HRT or SRT was observed.

Environmental Monitoring↗

PubMed2005

Corticotropin-releasing factor 1 receptor-mediated mechanisms inhibit colonic hypersensitivity in rats.

The potential relationship between stress and irritable bowel syndrome (IBS) symptomatology suggests a possible role for stress-mediating hormones, such as corticotropin-releasing factor (CRF), in the altered perception of stimuli in IBS patients. In previous studies, Wistar-Kyoto (WKY) rats with genetic indices of high anxiety demonstrated colonic hypersensitivity coupled with a high basal level of CRF within the central nervous system. In the current study we tested the hypothesis that a selective, non-peptide CRF1 receptor antagonist, antalarmin, would inhibit hypersensitivity in the WKY rat colon. Colonic sensitivity was determined by monitoring a visceromotor behavioural response during innocuous levels of colorectal distention (30 mmHg). In high anxiety WKY rats we found that antalarmin (20 mg kg-1, i.p.) significantly decreased the visceromotor response induced by colorectal distention. In a second study central administration (i.c.v.) of CRF was used to induce colonic hypersensitivity in lower anxiety Fischer 344 (F-344) rats, and in this model, antalarmin significantly inhibited the CRF-induced colonic hypersensitivity. In summary, a selective CRF1 receptor antagonist, antalarmin, inhibits colonic hypersensitivity apparent in WKY rats or in F-344 rats given a central administration of CRF. Our findings suggest that CRF1 receptor antagonism may represent a novel therapeutic approach for the treatment of IBS.

Animals↗

PubMed2004

Manipulation of a single charge in a double quantum dot.

We manipulate a single electron in a fully tunable double quantum dot using microwave excitation. Under resonant conditions, microwaves drive transitions between the (1,0) and (0,1) charge states of the double dot. Local quantum point contact charge detectors enable a direct measurement of the photon-induced change in occupancy of the charge states. From charge sensing measurements, we find T1 approximately 16 ns and a lower bound estimate for T*(2) of 400 ps for the charge two-level system.

Journal Article↗

PubMed2004

Coulomb-modified Fano resonance in a one-lead quantum dot.

We investigate a tunable Fano interferometer consisting of a quantum dot coupled via tunneling to a one-dimensional channel. In addition to Fano resonance, the channel shows strong Coulomb response to the dot, with a single electron modulating channel conductance by factors up to 100. Where these effects coexist, line shapes with up to four extrema are found. A model of Coulomb-modified Fano resonance is developed and gives excellent agreement with experiment.

Journal Article↗

PubMed2004

Differential charge sensing and charge delocalization in a tunable double quantum dot.

We report measurements of a tunable double quantum dot, operating in the quantum regime, with integrated local charge sensors. The spatial resolution of the sensors allows the charge distribution within the double dot system to be resolved at fixed total charge. We use this readout scheme to investigate charge delocalization as a function of temperature and strength of tunnel coupling, demonstrating that local charge sensing can be used to accurately determine the interdot coupling in the absence of transport.

Journal Article↗

PubMed2001

Removal of endocrine-disrupting chemicals in activated sludge treatment works.

The release of endocrine-disrupting chemicals into the aquatic environment has raised the awareness of the central role played by sewage treatment in lowland water quality. This review focuses on the activated sludge process, which is commonly used to treat sewage in large towns and cities and which successfully removes the bulk of the organic compounds that enter the works. However, not all compounds are completely broken down or converted to biomass. For example, the estrogenic alkylphenols and steroid estrogens found in effluent are the breakdown products of incomplete breakdown of their respective parent compounds. Batch microcosm studies have indicated that estrone, ethinylestradiol, and alkylphenols will not be completely eliminated in activated sludge over typical treatment times. Field data suggest that the activated sludge treatment process can consistently remove over 85% of estradiol, estriol, and ethinylestradiol. The removal performance for estrone appears to be less and is more variable. Because of its relatively high hydrophobicity, the accumulation of alkylphenol in sludge has been observed. Although it has not been examined, accumulation of ethinylestradiol in sludge is a possibility due to its recalcitrance and hydrophobicity. A comparison between the concentrations of some of the major endocrine-active chemicals in effluents and their biological potencies has been made, to direct attention to the chemicals of most concern. While water purification techniques such as UV or activated charcoal could significantly remove these microorganic contaminants, the high costs involved suggest that research into the potential for treatment optimization should receive more attention.

Animals↗

PubMed2001

Penetration of herbicides to groundwater in an unconfined chalk aquifer following normal soil applications.

The persistence and penetration of the herbicides isoproturon and chlorotoluron in an unconfined chalk aquifer has been monitored over a 4-year period through soil sampling, shallow coring and groundwater monitoring. Chlorotoluron was applied on plots as a marker compound, having never been used previously on that, or surrounding fields. The fieldsite had a 5 degree slope with soil depths of 0.5 to 1.5 m and a water table between 20 and 5 m from the soil surface. Where the water table was deepest (9-20 m below surface (mbs)) little or no positive herbicide detections were made. However, where the water table was at only 4-5 mbs, a regular pesticide signal of around 0.1 microg/l for isoproturon and chlorotoluron could be distinguished. Over the winter recharge period automatic borehole samplers revealed a series of short-lived peaks of isoproturon and chlorotoluron reaching up to 0.8 microg/l. This is consistent with a preferential flow mechanism operating at this particular part of the field. Such peaks were occurring over 2 years after the last application of these compounds. Shallow coring failed to uncover any significant pesticide pulse moving through the deep unsaturated zone matrix at the fieldsite.

Environmental Monitoring↗

PubMed2001

p53 Homologue p63 represses epidermal growth factor receptor expression.

Tumor suppressor p53 has been shown to transactivate epidermal growth factor receptor (EGFR) expression through binding to a putative p53 responsive element in the EGFR promoter between nucleotides -265 and -239 (EGFRp53RE). Isotypes of p63 gene products, recently identified as p53 relatives, have a similar function to transactivate several p53 target gene promoters. However, our results indicate that TAp63gamma has a very low ability to bind to the EGFRp53RE and surprisingly represses both basal EGFR promoter activity and endogenous EGFR expression. Transient transfection assays show that the EGFR promoter region between -348 and -293, containing two Sp1 sites, is crucial for the repression of the EGFR expression by TAp63gamma. Mutations in these Sp1 sites in the reporter constructs result in loss of the TAp63gamma repression effect. We further show that TAp63gamma directly interacts with Sp1 by immunoprecipitation analysis and that TAp63gamma impairs Sp1 binding to the target DNA site in electrophoretic mobility shift assays. These results suggest that TAp63gamma is involved in the regulation of the EGFR gene expression through interactions with basal transcription factors.

DNA↗