Search PubMed⌕ Search

Biomedical subjects

M B Jones

Publications and source records attributed to M B Jones.

At least 19 recordsLinked to original sources

The potential of ecotoxicoproteomics in environmental monitoring: biomarker profiling in mussel plasma using ProteinChip array technology.

New global technologies, allowing simultaneous analysis of thousands of genes, proteins, and metabolites (so-called "omics" technologies), are being adopted rapidly by industry, academia, and regulatory agencies. This study evaluated the potential of proteomics in ecotoxicological research (i.e., ecotoxicoproteomics). Filter-feeding mussels (Mytilus edulis) were exposed continuously for 3 wk to oil, or oil spiked with alkylphenols and extra polycyclic aromatic hydrocarbons. The influence of chronic exposure on mussel plasma protein expression was investigated utilizing ProteinChip array technology in combination with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF MS). Results indicated that exposure to spiked oil had a more significant effect on protein expression in mussels than oil alone. In total, 83 mass peaks (intact or modified proteins/peptides) were significantly altered by spiked oil, while 49 were altered by oil. In exposed organisms, the majority of peaks were upregulated compared to controls (i.e., 69% in oil and 71% in spiked oil). Some peaks (32 in total) were affected by both treatments; however, the degree of response was higher in the spiked oil group for 25 of the 32 commonly affected features. Additionally, certain peaks revealed exposure- or gender-specific responses. Multivariate analysis with regression tree-based methods detected protein patterns associated with exposure that correctly classified masked samples with 90-95% accuracy. Similarly, 92% of females and 85% of males were correctly classified (independent of exposure). Results indicate that proteomics have the potential to make a valuable contribution to environmental monitoring and risk assessment.

Animals↗

The effect of the lipid layer on tear film behaviour.

This paper investigates the effect of surfactants during tear film deposition and subsequent thinning. The surfactants occur naturally on the surface of the tear film in the form of a lipid layer. A lubrication model is developed that describes lipid spreading and film height evolution. It is shown that lipids may play an important role in drawing the tear film up the cornea during the opening phase of the blink. Further, nonuniform distributions of lipids may lead to a rapid thinning of the tear film behind the advancing lipid front (shock). Experiments using a fluorescein dye technique and using a tearscope were undertaken in order to visualise the motion of the lipid layer and any associated shocks immediately after a blink. It is found that the lipid layer continues to spread upwards on the cornea after the opening phase of the blink, in agreement with the model. Using the experimental data, lipid particles were tracked in order to determine the surface velocity and these results are compared to the model predictions.

Blinking↗

Dynamics of tear film deposition and draining.

This paper investigates the deposition of the tear film on the cornea of the human eye. The tear film is laid down by the motion of the upper eyelid and then subsequently flows and thins. Of particular interest is the stability of the tear layer and the development of dry patches on the cornea. While there has been significant research on the behaviour of tear films between blinks, this paper focuses on understanding the mechanisms which control the shape and thickness of the deposited film and how this affects the subsequent film behaviour. Numerical and analytical methods are applied to a lubrication model which includes the effects of surface tension, viscosity, gravity and evaporation. The model reveals the importance of the eyelid velocity, motion of the surface lipid layer and the storage of tear film between blinks.

Cornea↗

Differential sensitivity of three marine invertebrates to copper assessed using multiple biomarkers.

Understanding how biomarkers relate to each other on exposure to particular contaminants in different species is key to their widespread application in environmental management. However, few studies have systematically used multiple biomarkers in more than a single species to determine the variability of sublethal effects of a particular contaminant. In this study, three marine invertebrates, the shore crab Carcinus maenas, the common limpet Patella vulgata and the blue mussel Mytilus edulis, were exposed over 7 days in the laboratory to environmentally realistic concentrations of the priority pollutant copper. A combination of molecular, cellular and physiological biomarkers was measured in each organism to detect the toxic effects of copper. Biomarkers included lysosomal stability (neutral red retention), neurotoxicity (acetylcholinesterase activity), metabolic impairment (total haemolymph protein), physiological status (heart rate) and induction of protective metallothionein proteins. P. vulgata was the most sensitive to copper with significant effects measured in all biomarkers at concentrations of 6.1 microg Cu l(-1). In C. maenas, cellular and neurotoxic endpoints were affected significantly only at 68.1 microg Cu l(-1). Exposure to copper also induced metallothionein production in crabs. Over a 7-day exposure period, M. edulis was the most tolerant species to copper with significant effects being observed at the cellular level only at 68.1 microg Cu l(-1) . In all three species, cellular and neurotoxic pathways were more sensitive to disruption than physiological processes (protein and heart rate). Results illustrate how a suite of biomarkers applied to different sentinel species can provide a 'diagnosis of stress', whereby, effects at the molecular level can be used to interpret the level of physiological impairment of the organism.

Acetylcholinesterase↗

Biomarker responses and PAH uptake in Mya truncata following exposure to oil-contaminated sediment in an Arctic fjord (Svalbard).

Expanding industrial activity (notably oil and gas exploration) in the Arctic requires assessment of the potential impact of chemicals on marine organisms living in seawater at low temperature. The bivalve Mya truncata is common in Svalbard fjord (Norway) where it experiences low temperature throughout the year. To measure the impact of polycyclic aromatic hydrocarbons (PAH) on M. truncata, the responses of three biomarkers [total oxyradical scavenging capacity-assay (TOSC), plasma membrane stability of haemocytes and respiration rates] were investigated from bivalves exposed to sediment contaminated with a PAH mixture (crude oil). After two weeks of exposure to the contaminated sediment, TOSC showed no change. The high TOSC value (4010+/-1339 unit mg(-1) protein) of Mya truncata (control group) is thought to protect biomolecules with a low turnover rate efficiently in a low food availability environment. In the exposed bivalves, the haemocyte cellular membranes were significantly destabilised compared with controls (P<0.05). Respiration rate of control and PAH-exposed individuals (0.055+/-0.020 mg O(2) dw(-1) h(-1)) was similar and relatively low as is typical for polar bivalves, reflecting a strategy to minimise energy expenditure to cope with 9 months of starvation. Bioaccumulation of PAH by M. truncata was also low, due probably to a combination of low metabolic rate and reduced solubility of the oil compounds at low temperature. Data indicated an uptake of mainly low molecular weight compounds (two and three ring molecules). A good correlation of logBAF(lipid) (bioaccumulation factor) and logK(ow) (octanol/water partitioning coefficient) was shown (r(2)=0.87). Tissue sensitivity and/or functional differences (digestive gland vs. haemocytes), PAH uptake route (dietary vs. gills), the low metabolic rate of M. truncata and the low environmental temperature (reducing the bioavailability of PAH) are factors that help explain these findings.

Animals↗

A copepod life-cycle test and growth model for interpreting the effects of lindane.

A full life-cycle test was performed to measure the effects of lindane (3.2-3,200 microg l(-1)) on the survival, development and reproduction of the freshwater copepod Bryocamptus zschokkei. This copepod survived at relatively high concentrations of lindane compared with other freshwater crustaceans with a 10 day LC50 of 241 microg l(-1) (95% CL of 141-440). 'Equiproportional development', which assumes that each moult stage represents a specific proportion of the total development time, and is not affected by processes that influence metabolism such as temperature and food quality, was used to determine the mode of action of lindane on development in B. zschokkei. Development to adult was significantly longer at 100 microg l(-1) lindane compared with the controls, however, development remained equiproportional regardless of lindane exposure. Increased development times, therefore, are not due to a direct effect of lindane on the moulting process but are due probably to reduced food intake or increased metabolism through the stress imposed by toxicant exposure. Although the survival data suggest that B. zschokkei is relatively tolerant of lindane exposure, reproduction was affected at low lindane concentrations. At 32 microg l(-1) lindane, significantly fewer eggs and viable offspring were produced per female compared with the solvent control. At very low lindane concentrations (3.2 and 10 microg l(-1)), there was a significant increase in the numbers of offspring produced per female compared with the controls and this is interpreted as a hormesis effect. In conclusion, a full life-cycle test demonstrated B. zschokkei is relatively sensitive to lindane compared with other freshwater crustaceans. Incorporating a copepod growth model (equiproportional development) into the life-cycle test design, provided information on the dominant mode of action of the toxicant.

Animals↗

Assessment of the aversive consequences of acute and chronic administration of the melanocortin agonist, MTII.

BACKGROUND: The synthetic melanocortin (MC) agonist, melanotan-II (MTII), reduces food intake and body weight for hours to days after administration. One early report on the effect of MTII suggested that part of its anorexic action may be mediated by aversive consequences. In that experiment, MTII was found to support a mild conditioned taste aversion (CTA). OBJECTIVE: The present experiments replicate and extend those findings in two additional CTA paradigms to further characterize the aversive effects of MTII in rats. METHODS: Experiment 1 simultaneously assessed the ability of MTII to support CTA and reduce food intake, using a small oral infusion of a novel taste as the conditioned stimulus. Experiment 2 assessed the aversive consequences of chronic MTII administration. To accomplish this, we paired implantation of lithium chloride (LiCl)-, MTII- or saline-containing osmotic minipumps with a constantly available novel flavor. After 7 days, rats received a choice test between the minipump-paired flavor and a previously available neutral flavor. RESULTS: Rats with saline minipumps exhibited no preference for either flavor. By contrast, rats in both the LiCl and MTII minipump groups significantly preferred the neutral flavor, indicating the development of a CTA. Additionally, CTA produced by administration of MTII was found to be more resistant to extinction than that produced by LiCl. CONCLUSIONS: The reduction in food intake caused by MTII is accompanied by aversive consequences regardless of route of administration. These results present difficulties for the development of MCs-based therapies for obesity.

Animals↗

Heart rate, respiration and total oxyradical scavenging capacity of the Arctic spider crab, Hyas araneus, following exposure to polycyclic aromatic compounds via sediment and injection.

Increasing industrial activity in the European Arctic has raised concerns of the potential anthropogenic impact of chemicals on this polar marine ecosystem. For the past 20 years or so, biomarkers have been developed to provide early-warning signals of detrimental impacts of chemicals on the marine ecosystem, however, most biomarker methods have been established for organisms living in temperate rather than polar waters. Little is known about biomarker responses in organisms living within the temperature range of -1.88 to +5 degrees C. In this study, established biomarkers from temperate studies were tested on the Arctic spider crab Hyas araneus to validate their use in polar ecosystems. H. araneus is common in Svalbard fjord (Norway), although it is a temperate water species occurring from northern Spain to Svalbard at depths from 10 to 1200 m. In this paper, the effects of oil were investigated at 2 degrees C via two routes: (i) injection and (ii) contaminated sediment. After 2 weeks of exposure, heart rate, oxygen consumption and total oxyradical scavenging capacity (TOSC) were measured in the same individuals. In both methods of contaminant exposure, heart rate showed a significant increase compared with the control (P < 0.0001, n = 7); mean heart rate values (+/- S.D.) of H. araneus were 49.06 (+/- 13.72), 57.56 (+/- 7.28) and 63.30 (+/- 6.57) beats per minute in control, injected and sediment-treated groups, respectively. Respiration of H. araneus was not affected significantly by either oil treatment (P > 0.05), but two individuals (n = 8) showed a marked increase in oxygen uptake in the sediment-exposed group. The basal oxygen consumption of control H. araneus was lower (0.025 mg O(2) g wet wt.(-1) h(-1)) than reported for H. araneus living in temperate water. Although TOSC of H. araneus was not affected significantly by either exposure treatment (P > 0.05) the mean TOSC value in the sediment-exposed group was lower than the control, indicating some saturation of the oxyradical scavenging system. Results indicate that although low temperature appears to be the main factor reducing the bioavailability of polycyclic-aromatic hydrocarbons, the relatively low metabolic rate of Arctic H. araneus is also implicated in decreased uptake and metabolism of oil compounds into reactive oxygen species (ROS).

Animals↗

Trace metal uptake by the Chinese mitten crab Eriocheir sinensis: the role of osmoregulation.

Changes in salinity affect the bioavailability and consequent uptake of trace metals by euryhaline invertebrates. In many cases, salinity-related effects on metal uptake can be explained by changes in chemical speciation but salinity may also influence uptake indirectly through its action on osmoregulatory mechanisms. Specifically, it can be hypothesised that trace metal uptake may be reduced at salinities approaching the isosmotic point of a species because, at this point, there is reduced activity of ionic exchange pumps. The present study tested this hypothesis using the Chinese mitten crab, Eriocheir sinensis, a hyper-hypoosmoregulator with an isosmotic point around 33 per thousand. Crabs were exposed to radio-labelled cadmium and zinc at 23, 33 and 43 per thousand for 4 days. To eradicate speciation effects, crabs were exposed to the same concentration of the radio-labelled free metal ion (estimated using MineQL computer software) at each salinity. Haemolymph samples were taken daily and radio-labelled metal concentrations were estimated from radioactivity counts and used to provide relative measures of metal uptake. Neither cadmium nor zinc uptake was lowest at the isosmotic point. The uptake of cadmium increased significantly with increase in salinity, while the uptake of zinc showed no significant change with increased salinity. Thus changes in trace metal uptake rates in E. sinensis do not appear to be controlled only by changes in free metal ion concentrations. The different effects of salinity change on the uptake of cadmium and zinc (in the absence of free metal ion change) also indicate that physiological responses to osmotic change alone do not control metal uptake rates for this species.

Animals↗

Magnetic resonance imaging of denervation-induced muscle atrophy: effects of clenbuterol in the rat.

We show that magnetic resonance imaging (MRI) can be used to quantify the amount of muscle in the lower legs of adult rats and to noninvasively monitor the onset and progression of denervation-induced atrophy. Muscle cross-sectional areas determined from 2D gradient-echo MR images allow longitudinal quantification of the protective effects of a beta(2)-adrenergic agonist clenbuterol. We also show that the estimation of clenbuterol's efficacy is improved by computation of the muscle volume. Rapid animal throughput and the ability to accurately estimate efficacy make MRI an attractive technology for studying skeletal muscle atrophy and hypertrophy, allowing the evaluation of potential therapies in longitudinal studies.

Animals↗

Impairment of mysid (Neomysis integer) swimming ability: an environmentally realistic assessment of the impact of cadmium exposure.

Neomysis integer (Crustacea: Mysidacea), a euryhaline member of the hyperbenthos of the upper reaches of European estuaries, has been identified as a suitable animal for assessing the impacts of chemical pollutants on these estuarine regions. In this study, the effect of a 7 day pre-exposure to environmentally relevant concentrations of cadmium (0.5 and 1.0 microg l(-1)) on the swimming behaviour of N. integer was examined using an annular flume. Cadmium speciation at two salinities (1 and 10 per thousand) that dominate these upper estuarine regions was modelled to ensure mysids were exposed to the same concentration of the toxic free-ion at each salinity. There was no significant difference in the swimming behaviour of mysids exposed to the same free-ion cadmium concentration at the two different salinities. At each salinity, exposure to 0.5 microg Cd2+ (aq) l(-1)resulted in fewer mysids moving forward into the current (normal behaviour) at free stream velocities typical of their natural habitat (e.g. 3-9 cm s(-1)) than non cadmium-exposed mysids. At these low current speeds, cadmium-exposed mysids were either able to maintain position or were swept by the current. The same general responses were recorded for mysids exposed to 1.0 microg Cd2+ (aq) l(-1)except that more mysids showed disrupted swimming ability compared with 0.5 microg Cd2+ (aq) l(-1). At higher current speeds (>12 cm s(-1)), current velocity was the dominant factor affecting mysid swimming behaviour and there was no effect of cadmium on mysids maintaining position. Exposure to cadmium also caused significant disruption of the hyperbenthic behaviour of N. integer and more cadmium-exposed individuals were in the water column than control mysids; this result was more variable at 10 per thousand than 1 per thousand. Results indicate that exposure to cadmium concentrations of 0.5 microg Cd2+(aq) l(-1)would result in displacement of N. integer from its optimum region within the estuarine environment. This conclusion would not be achieved from standard LC(50) tests (e.g. 7 day LC50 = 2.95 microg Cd2+ (aq) l(-1)), highlighting the value of behavioural disruption as a sensitive indicator of environmental chemical contamination.

Animals↗

The relationship between trace metal contamination and stream meiofauna.

The effect of chemical contaminants on freshwater meiofaunal communities is poorly understood and meiofauna rarely form part of environmental impact assessments in fresh waters. The community composition and diversity of meiofauna in streams of southwest England (Cornwall) representing a gradient in trace metal contamination were investigated. Multivariate and univariate statistical techniques were used to correlate community composition, diversity and environmental variables. Meiofaunal communities were very different at sites with high compared with low metal concentrations. Copper, either singly, or in combination with other environmental variables (aluminium, zinc or dissolved organic carbon), was the most important correlate with community composition. Not all meiofaunal species were adversely affected by metals, however, and some taxa, most notably certain cyclopoid copepods, were abundant at high metal concentrations. Moreover, sites with high metal concentrations were not significantly less diverse than sites of low metal concentrations. These data suggest that metal contamination significantly alters the composition of stream meiofaunal assemblages and highlight the importance of including meiofauna in impact studies of fresh waters.

Animals↗

Efficacy and safety of 'hot' tonsillectomy.

Recurrent acute tonsillitis, peritonsillar infections and quinsy (peritonsillar abscess) are common clinical conditions that present to a general practitioner. Management in general practice and in hospital is confounded by apparently conflicting treatment options in the medical literature. We have developed clear guidelines as part of an ongoing audit cycle which include performing quinsy or 'hot' tonsillectomy in selected cases, alongside conservative treatments to ensure the speedy recovery and minimal hospitalisation of all patients, with resultant cost benefits.

Acute Disease↗

Effects of salinity and chemical speciation on cadmium accumulation and toxicity to two mysid species.

The estuarine environment is characterized by frequent fluctuations in salinity. Consequently, organisms used for environmental monitoring of estuaries must be euryhaline so that their laboratory responses to chemical pollutants are measured under the full range of salinity exposures experienced in the field. Neomysis integer and Praunus flexuosus are two potential candidates for use in environmental monitoring of European estuaries. The present study assesses the effects of salinity on survival, trace metal accumulation, and toxicity to these two mysid species. Neomysis integer was more euryhaline, showing 100% survival at 1 to 40@1000 compared with P. flexuosus, which showed 100% survival at salinities of 10 to 40@1000. Toxicity of the free cadmium ion to both species was unaffected by salinity, and 96-h LC50s ranged from 4.8 to 15 micrograms Cd2+/L for N. integer and from 12.3 to 16 micrograms Cd2+/L for P. flexuosus. The 7-d LC50s ranged from 1.0 to 4.2 and 4.8 to 5.3 micrograms Cd2+/L for N. integer and P. flexuosus, respectively. No effect of exposure salinity was found on cadmium body burdens of mysids exposed for 7 d to 0.5 and 1.0 microgram Cd2+/L. The results are discussed in terms of possible effects of osmoregulatory mechanisms on trace metal uptake, accumulation, and toxicity.

Animals↗

Effects of a tartar control whitening dentifrice on tooth shade in a population with long-standing natural stain.

Changing and whitening tooth color in people with long-standing tooth stain without excessive hard tissue abrasion may represent one of the more difficult challenges for whitening dentifrices. An eight-week clinical trial was conducted to evaluate change in tooth color by a silica-based, enamel-safe tartar control whitening dentifrice compared to a marketed baking soda dentifrice control. First, a screening exercise was conducted to identify individuals with long-standing extrinsic dental stain. This exercise targeted adults who reported "stained teeth" and coffee/tea drinking or smoking, but who had no recent history of dental prophylaxis. Targeted subjects were examined for stain (Lobene Index) and tooth shade/color (Vita). A total of 291 adults having extrinsic stain and discolored teeth were enrolled in the study. Subjects were randomized to one of the two treatment groups, and all dentifrice use was unsupervised. Tooth color was measured at 4 and 8 weeks from shade values collected from the 8 incisors, and averages were determined from a linear ordering of the shade guide. A total of 278 evaluable subjects completed the 8-week study. Overall, the tartar control whitening dentifrice group experienced an improvement in color, differing statistically from baseline (p < 0.001) and from the marketed control (p < 0.05). Safety profiles for the two dentifrices were generally similar. Among patients with long-standing extrinsic stain, use of the tartar control whitening dentifrice resulted in superior overall tooth shade and reduced maximum or worst color compared to the marketed baking soda dentifrice control.

Adult↗

Activation and inhibition of G protein-coupled inwardly rectifying potassium (Kir3) channels by G protein beta gamma subunits.

G protein-coupled inwardly rectifying potassium (GIRK) channels can be activated or inhibited by different classes of receptors, suggesting a role for G proteins in determining signaling specificity. Because G protein betagamma subunits containing either beta1 or beta2 with multiple Ggamma subunits activate GIRK channels, we hypothesized that specificity might be imparted by beta3, beta4, or beta5 subunits. We used a transfection assay in cell lines expressing GIRK channels to examine effects of dimers containing these Gbeta subunits. Inwardly rectifying K(+) currents were increased in cells expressing beta3 or beta4, with either gamma2 or gamma11. Purified, recombinant beta3gamma2 and beta4gamma2 bound directly to glutathione-S-transferase fusion proteins containing N- or C-terminal cytoplasmic domains of GIRK1 and GIRK4, indicating that beta3 and beta4, like beta1, form dimers that bind to and activate GIRK channels. By contrast, beta5-containing dimers inhibited GIRK channel currents. This inhibitory effect was obtained with either beta5gamma2 or beta5gamma11, was observed with either GIRK1,4 or GIRK1,2 channels, and was evident in the context of either basal or agonist-induced currents, both of which were mediated by endogenous Gbetagamma subunits. In cotransfection assays, beta5gamma2 suppressed beta1gamma2-activated GIRK currents in a dose-dependent manner consistent with competitive inhibition. Moreover, we found that beta5gamma2 could bind to the same GIRK channel cytoplasmic domains as other, activating Gbetagamma subunits. Thus, beta5-containing dimers inhibit Gbetagamma-stimulated GIRK channels, perhaps by directly binding to the channels. This suggests that beta5-containing dimers could act as competitive antagonists of other Gbetagamma dimers on GIRK channels.

Binding Sites↗

Proteomic analysis of the atrophying rat soleus muscle following denervation.

A proteomic analysis was performed comparing normal rat soleus muscle to denervated soleus muscle at 0.5, 1, 2, 4, 6, 8 and 10 days post denervation. Muscle mass measurements demonstrated that the times of major mass changes occurred between 2 and 4 days post denervation. Proteomic analysis of the denervated soleus muscle during the atrophy process demonstrated statistically significant (at the p < 0.01 level) changes in 73 soleus proteins, including coordinated changes in select groups of proteins. Sequence analysis of ten differentially regulated proteins identified metabolic proteins, chaperone and contractile apparatus proteins. Together these data indicate that coordinated temporally regulated changes in the proteome occur during denervation-induced soleus muscle atrophy, including changes in muscle metabolism and contractile apparatus proteins.

Animals↗