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Biomedical subjects

A K Jones

Publications and source records attributed to A K Jones.

At least 19 recordsLinked to original sources
PubMed2007

ShAR2beta, a divergent nicotinic acetylcholine receptor subunit from the blood fluke Schistosoma.

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that mediate the fast actions of the neurotransmitter, acetylcholine. Invertebrate nAChRs are of interest as they are targets of widely-selling insecticides and drugs that control nematode parasites. Here, we report the cloning of ShAR2beta, a candidate nAChR subunit from the blood fluke, Schistosoma haematobium, which is the third trematode nAChR subunit to be characterized. While ShAR2beta possesses key structural features common to all nAChRs, its amino acid sequence shares considerably low identity with those of insect, nematode and vertebrate nAChR subunits. In particular, the second transmembrane domain of ShAR2beta, which lines the ion channel, bears unusual amino acid residues which will likely give rise to a receptor with distinct functional properties. Phylogenetic analysis shows that ShAR2beta is a divergent nAChR subunit that may define a clade of trematode-specific subunits. We discuss our findings in the context of potentially exploiting this receptor as a target for controlling schistosome parasites.

Amino Acid Sequence↗
PubMed2006

Contributions from Caenorhabditis elegans functional genetics to antiparasitic drug target identification and validation: nicotinic acetylcholine receptors, a case study.

Following the complete sequencing of the genome of the free-living nematode, Caenorhabditis elegans, in 1998, rapid advances have been made in assigning functions to many genes. Forward and reverse genetics have been used to identify novel components of synaptic transmission as well as determine the key components of antiparasitic drug targets. The nicotinic acetylcholine receptors (nAChRs) are prototypical ligand-gated ion channels. The functions of these transmembrane proteins and the roles of the different members of their extensive subunit families are increasingly well characterised. The simple nervous system of C. elegans possesses one of the largest nicotinic acetylcholine receptor gene families known for any organism and a combination of genetic, microarray, physiological and reporter gene expression studies have added greatly to our understanding of the components of nematode muscle and neuronal nAChR subtypes. Chemistry-to-gene screens have identified five subunits that are components of nAChRs sensitive to the antiparasitic drug, levamisole. A novel, validated target acting downstream of the levamisole-sensitive nAChR has also been identified in such screens. Physiology and molecular biology studies on nAChRs of parasitic nematodes have also identified levamisole-sensitive and insensitive subtypes and further subdivisions are under investigation.

Animals↗
PubMed2006

Tomographic physical phantom of the newborn child with real-time dosimetry I. Methods and techniques for construction.

A tomographic phantom representing a newborn female patient was constructed using tissue-equivalent materials previously developed at the University of Florida. This phantom was constructed using contoured images from an actual patient data set, a whole-body computed tomography of a newborn cadaver previously described by Nipper et al. [Phys. Med. Biol. 47, 3143-1364 (2002)]. Four types of material are incorporated in the phantom: soft tissue, bone tissue, lung tissue, and air. The phantom was constructed on a slice-by-slice basis with a z-axis resolution of 5 mm, channels for dosimeters (thermoluminescent dosimeter (TLD), metal-oxide-semiconductor field-effect transistor, or gated fiber-optic-coupled dosimeter (GFOC)) were machined into slices prior to assembly, and the slices were then fixed together to form the complete phantom. The phantom will be used in conjunction with an incorporated dosimetry system to calculate individual organ and effective doses delivered to newborn patients during various diagnostic procedures, including, but not limited to, projection radiography and computed tomography. Included in this paper are images detailing the construction process, and images of the completed phantom.

Computer Systems↗
PubMed2006

Selenium supplementation of lactating dairy cows: effect on selenium concentration in blood, milk, urine, and feces.

The objectives were to determine effects of graded levels of selenized yeast derived from a specific strain of Saccharomyces cerevisiae (CNCM I-3060) on animal performance and in selenium concentrations in the blood, milk, feces, and urine of dairy cows compared with sodium selenite; and to provide preliminary data on the proportion of selenium as selenomethionine in the milk and blood. Twenty Holstein cows were used in a 5 x 5 Latin square design study in which all cows received the same total mixed rations, which varied only in source or concentration of dietary selenium. There were 5 experimental treatments. Total dietary selenium of treatment 1, which received no added selenium, was 0.15 mg/kg of dry matter, whereas values for treatments 2, 3, and 4, derived from selenized yeast, were 0.27, 0.33, and 0.40 mg/kg of dry matter, respectively. Treatment 5 contained 0.25 mg of selenium obtained from sodium selenite/kg of dry matter. There were no significant treatment effects on animal performance, and blood chemistry and hematology showed few treatment effects. Regression analysis noted significant positive linear effects of increasing dietary selenium derived from selenized yeast on selenium concentrations in the milk, blood, urine, and feces. In addition, milk selenium results indicated improved bioavailability of selenium from selenized yeast, compared with sodium selenite. Preliminary analyses showed that compared with sodium selenite, the use of selenized yeast increased the concentration of selenomethionine in the milk and blood. There was no indication of adverse effects on cow health associated with the use of selenized yeast.

Animal Feed↗
PubMed2005

Sgbeta1, a novel locust (Schistocerca gregaria) non-alpha nicotinic acetylcholine receptor-like subunit with homology to the Drosophila melanogaster Dbeta1 subunit.

The cloning, sequencing and functional expression of Sgbeta1, a novel locust (Schistocerca gregaria) non-alpha nicotinic acetylcholine receptor (nAChR) subunit is described. This subunit shows 80% identity with the Drosophila melanogaster Dbeta1 and 92% identity with the Locusta migratoria beta1, non-alpha subunits but only 38% identity to Sgalpha1 (also referred to as alphaL1), a previously cloned S. gregaria nAChR alpha-subunit. When expressed in Xenopus laevis oocytes, Sgbeta1 does not respond to nicotine. Responses to nicotine are observed, however, in oocytes co-expressing Sgalpha1 and Sgbeta1, but the pharmacology is indistinguishable from that of currents produced by expressing Sgalpha1 alone. We conclude that either Sgbeta1 does not co-assemble with Sgalpha1, or that it is unable to contribute to the functional properties of the receptor, in the Xenopus oocyte expression system.

Amino Acid Sequence↗
PubMed2005

Edit, cut and paste in the nicotinic acetylcholine receptor gene family of Drosophila melanogaster.

Nicotinic acetylcholine receptors (nAChRs) are important for fast synaptic cholinergic transmission. They are targets of drugs/chemicals for human and animal health as well as for pest control. With the advent of genome sequencing, entire nAChR gene families have now been described for vertebrates and invertebrates. Mostly, these are extensive with a large number of distinct subunits, making possible many nAChR subtypes differing in transmitter affinity, channel conductance, ion selectivity, desensitization, modulation and pharmacology. The smallest nAChR gene family to date is that of the fruit fly, Drosophila melanogaster, with only 10 members. This apparently compact family belies its true diversity as 4 of the 10 subunits show alternative splicing. Also, using Drosophila, A-to-I pre-mRNA editing has been demonstrated for the first time in nAChRs. Such is the extent of this variation, that one subunit alone (Dalpha6) can potentially generate far more isoforms than seen in entire gene families from other species. We present here three-dimensional models constructed for insect nAChRs, which show that many variations introduced by alternative splicing and RNA editing may influence receptor function.

Alternative Splicing↗
PubMed2005

MOSFET dosimeter depth-dose measurements in heterogeneous tissue-equivalent phantoms at diagnostic x-ray energies.

The objective of the present study was to explore the use of the TN-1002RD metal-oxide-semiconductor field effect transistor (MOSFET) dosimeter for measuring tissue depth dose at diagnostic photon energies in both homogeneous and heterogeneous tissue-equivalent materials. Three cylindrical phantoms were constructed and utilized as a prelude to more complex measurements within tomographic physical phantoms of pediatric patients. Each cylindrical phantom was constructed as a stack of seven 5-cm-diameter and 1-cm-thick discs of materials radiographically representative of either soft tissue (S), bone (B), or lung tissue (L) at diagnostic photon energies. In addition to a homogeneous phantom of soft tissue (SSSSSSS), two heterogeneous phantoms were constructed: SSBBSSS and SBLLBSS. MOSFET dosimeters were then positioned at the interface of each disc, and the phantoms were then irradiated at 66 kVp and 200 mAs. Measured values of absorbed dose at depth were then compared to predicated values of point tissue dose as determined via Monte Carlo radiation transport modeling. At depths exceeding 2 cm, experimental results matched the computed values of dose with high accuracy regardless of the dosimeter orientation (epoxy bubble facing toward or away from the x-ray beam). Discrepancies were noted, however, between measured and calculated point doses near the surface of the phantom (surface to 2 cm depth) when the dosimeters were oriented with the epoxy bubble facing the x-ray beam. These discrepancies were largely eliminated when the dosimeters were placed with the flat side facing the x-ray beam. It is therefore recommended that the MOSFET dosimeters be oriented with their flat sides facing the beam when they are used at shallow depths or on the surface of either phantoms or patients.

Child↗
PubMed2005

Effect of corn silage from an herbicide-tolerant genetically modified variety on milk production and absence of transgenic DNA in milk.

Data from 60 multiparous Holstein cows were used in a 12-wk continuous design feeding trial. Cows were allocated to 1 of 4 experimental treatments (T1 to T4). In T1 and T2, the total mixed ration (TMR) contained either corn silage from the genetically modified (GM) variety Chardon Liberty Link, which is tolerant to the herbicide glufosinate ammonium, or its near isogenic nonGM counterpart, whereas the TMR used in T3 and T4 contained corn silage from the commercially available nonGM varieties Fabius and Antares, respectively. The objectives of the study were to determine if the inserted gene produced a marked effect on chemical composition, nutritive value, feed intake, and milk production, and to determine if transgenic DNA and the protein expressed by the inserted gene could be detected in bovine milk. The nutritive value, fermentation characteristics, mineral content, and amino acid composition of all 4 silages were similar. There were no significant treatment effects on milk yield, milk composition, and yield of milk constituents, and the dry matter (DM) intake of the GM variety was not significantly different from the 2 commercial varieties. However, although the DM intake noted for the nonGM near-isogenic variety was similar to the commercial varieties, it was significantly lower when compared with the GM variety. Polymerase chain reaction analyses of milk samples collected at wk 1, 6, and 12 of the study showed that none of the 90 milk samples tested positive, above a detection limit of 2.5 ng of total genomic DNA/mL of milk, for either tDNA (event T25) or the single-copy endogenous Zea mays gene, alcohol dehydrogenase. Using ELISA assays, the protein expressed by the T25 gene was not detected in milk.

Acetyltransferases↗
PubMed2005

Chemical, physical, and sensory properties of dairy products enriched with conjugated linoleic acid.

Recent studies have illustrated the effects of cis-9,trans-11 conjugated linoleic acid (CLA) on human health. Ruminant-derived meat, milk and dairy products are the predominant sources of cis-9,trans-11 CLA in the human diet. This study evaluated the processing properties, texture, storage characteristics, and organoleptic properties of UHT milk, Caerphilly cheese, and butter produced from a milk enriched to a level of cis-9,trans-11 CLA that has been shown to have biological effects in humans. Forty-nine early-lactation Holstein-British Friesian cows were fed total mixed rations containing 0 (control) or 45 g/kg (on dry matter basis) of a mixture (1:2 wt/wt) of fish oil and sunflower oil during two consecutive 7-d periods to produce a control and CLA-enhanced milk, respectively. Milk produced from cows fed the control and fish and sunflower oil diets contained 0.54 and 4.68 g of total CLA/100 g of fatty acids, respectively. Enrichment of CLA in raw milk from the fish and sunflower oil diet was also accompanied by substantial increases in trans C18:1 levels, lowered C18:0, cis-C18:1, and total saturated fatty acid concentrations, and small increases in n-3 polyunsaturated fatty acid content. The CLA-enriched milk was used for the manufacture of UHT milk, butter, and cheese. Both the CLA-enhanced butter and cheese were less firm than control products. Although the sensory profiles of the CLA-enriched milk, butter, and cheese differed from those of the control products with respect to some attributes, the overall impression and flavor did not differ. In conclusion, it is feasible to produce CLA-enriched dairy products with acceptable storage and sensory characteristics.

Animals↗
PubMed2003

Tissue-equivalent materials for construction of tomographic dosimetry phantoms in pediatric radiology.

Tissue equivalent materials have a variety of uses, including routine quality assurance and quality control in both diagnostic and therapeutic physics. They are frequently used in a research capacity to measure doses delivered to patients undergoing various therapeutic procedures. However, very few tissue equivalent materials have been developed for research use at the low photon energies encountered in diagnostic radiology. In this paper, we present a series of tissue-equivalent (TE) materials designed to radiographically mimic human tissue at diagnostic photon energies. These tissue equivalent materials include STES-NB (newborn soft tissue substitute), BTES-NB (newborn bone tissue substitute), LTES (newborn as well as a child/adult lung tissue substitute), STES (child/adult soft tissue substitute), and BTES (child/adult bone tissue substitute). In all cases, targeted reference elemental compositions are taken from those specified in the ORNL stylized computational model series. For each material, reference values of mass density, mass attenuation coefficients (10-150 keV), and mass energy-absorption coefficients (10-150 keV) were matched as closely as permitted by material selection and manufacturing constraints. Values of mu/rho and mu(en)/rho for the newborn TE materials are noted to have maximum deviations from their ORNL reference values of from 0 to -3% and from +2% to -3%, respectively, over the diagnostic energy range 10-150 keV. For the child/adult TE materials, these same maximal deviations of mu/rho and mu(en)/rho are from +1.5% to -3% and from +3% to -3%, respectively. Simple calculations of x-ray fluence attenuation under narrow-beam geometry using a 66 kVp spectrum typical of newborn CR radiographs indicate that the tissue-equivalent materials presented here yield estimates of absorbed dose at depth to within 3.6% for STES-NB, 3.2% for BTES-NB, and 1.2% for LTES of the doses assigned to reference newborn soft, bone, and lung tissue, respectively.

Adult↗
PubMed2001

Source localisation of 62-electrode human laser pain evoked potential data using a realistic head model.

Laser evoked potentials (LEPs), elicited by painful laser stimulation of the right forearm, were recorded from 62 electrodes in a single healthy subject. The positions of the electrodes on the scalp were co-registered with the subject's structural magnetic resonance image (MRI) of the brain. Spatio-temporal dipole modelling, using a head model derived from the MRI, estimated sources in left posterior cingulate, posterior parietal and anterior insular cortices. The parietal source peaked in activity at 260 ms, which explained the N1/N2 peaks of the LEPs. The cingulate source was the most strongly activated, at 400 ms, and accounted for the P2 LEP component. The insular source showed late, prolonged activation, peaking in magnitude at 850 ms. This is the first study to report scalp-recorded LEP generators in posterior parietal and insular cortices. Although these sources require replication, they are consistent with other functional imaging studies.

Brain Mapping↗
PubMed2000

Fast voltammetric studies of the kinetics and energetics of coupled electron-transfer reactions in proteins.

A wealth of information on the reactions of redox-active sites in proteins can be obtained by voltammetric studies in which the protein sample is arranged as a layer on an electrode surface. By carrying out cyclic voltammetry over a wide range of scan rates and exploiting the ability to poise or pulse the electrode potential between cycles, data are obtained that are conveniently (albeit simplistically) analysed in terms of plots of peak potentials against scan rate. A simple reversible electron-transfer process gives rise to a 'trumpet'-shaped plot because the oxidation and reduction peaks separate increasingly at high scan rate; the electrochemical kinetics are then determined by fitting to Butler-Volmer or Marcus models. Much more interesting though are the ways in which this 'trumpet plot' is altered, often dramatically, when electron transfer is coupled to biologically important processes such as proton transfer, ligand exchange, or a change in conformation. It is then possible to derive particularly detailed information on the kinetics, energetics and mechanism of reactions that may not revealed clearly or even at all by other methods. In order to interpret the voltammetry of coupled systems, it is important to be able to define 'ideal behaviour' for systems that are expected to show simple and uncoupled electron transfer. Accordingly, this paper describes results we have obtained for several proteins that are expected to show such behaviour, and compares these results with theoretical predictions.

Electrochemistry↗
PubMed2000

Post stroke shoulder pain: more common than previously realized.

Stroke is a common disease often requiring rehabilitation, which may be prolonged by shoulder pain. The true incidence of post stroke shoulder pain has not been fully evaluated. In order to establish this, we undertook a prospective study of 123 consecutive patients with a diagnosis of acute stroke during a 6-month period. Patients were assessed by interview, full rheumatological and neurological examination, 14 days post stroke, for a history of shoulder pain according to predetermined criteria. In addition, Barthel Index, HAD score and pain scores were also recorded. Twenty-five percent of patients developed shoulder pain within 2 weeks of their stroke. There was a statistically significant association with ipsilateral sensory impairment (p < 0.005), abnormal rheumatological examination (p < 0.001) and depression score (p < 0.005). We conclude that post stroke shoulder pain is more common than previously realized and in addition to abnormal shoulder joint examination may also be associated with upper limb sensory impairment. Thorough neurological examination is required to detect sensory loss and hence establish patients at risk. This is probably best done by a structured proforma.

Aged↗
PubMed2000

Effect of monensin on milk production of Holstein-Friesian dairy cows.

We examined the effects of monensin on feed intake and milk production in Holstein-Friesian cows receiving a total mixed rations in two experiments. In experiment 1, 60 individually fed cows consumed, during wk 7 to 26 of lactation, 1 kg/d of supplement containing either 0, 150,300, or 450 mg of monensin. In experiment 2, 98 group-fed cows also received 1 kg/d of a supplement with either 0 or 300 mg/d of monensin for two consecutive lactations. In lactations 1 and 2, treatment started at wk 8 and 3 wk prior to calving, and continued for 32 wk. In experiment 1, 150, 300, and 450 mg of monensin/d produced a small decrease in feed intake and milk yield responses of 2.8, 2.5 and 1.5 kg/d, respectively. In experiment 2, milk yield responses of 0.8 and 1.1 kg/d were recorded in lactations 1 and 2. Milk fat and milk protein content declined in experiments 1 and 2, lactations 1 and 2 by 0.46, 0.38 and 0.27%, and 0.16, 0.16 and 0.11%, respectively. Yield of milk constituents was unaffected. Efficiency of milk production was increased by 5% in experiment 1. In experiment 2, lactation 2, monensin decreased beta-hydroxybutyrate and acetoacetate but increased blood glucose concentration.

3-Hydroxybutyric Acid↗
PubMed1999

The cortical representation of pain.

Anatomical and physiological studies in animals, as well as functional imaging studies in humans have shown that multiple cortical areas are activated by painful stimuli. The view that pain is perceived only as a result of thalamic processing has, therefore, been abandoned, and has been replaced by the question of what functions can be assigned to individual cortical areas. The following cortical areas have been shown to be involved in the processing of painful stimuli: primary somatosensory cortex, secondary somatosensory cortex and its vicinity in the parietal operculum, insula, anterior cingulate cortex and prefrontal cortex. These areas probably process different aspects of pain in parallel. Previous psychophysical research has emphasized the importance of separating pain experience into sensory-discriminative and affective-motivational components. The sensory-discriminative component of pain can be considered a sensory modality similar to vision or olfaction; it becomes more and more evident that it is subserved by its own apparatus up to the cortical level. The affective-motivational component is close to what may be considered 'suffering from pain'; it is clearly related to aspects of emotion, arousal and the programming of behaviour. This dichotomy, however, has turned out to be too simple to explain the functional significance of nociceptive cortical networks. Recent progress in imaging technology has, therefore, provided a new impetus to study the multiple dimensions of pain.

Animals↗
PubMed1999

The contribution of functional imaging techniques to our understanding of rheumatic pain.

The main cerebral components of the human pain matrix have been defined using functional imaging techniques. The experience of pain is likely to be elaborated as a result of parallel processing within this matrix. There is not, therefore, a single pain center. The determinants of pain are as likely to be determined by top-down as by bottom-up processes. The precise function of the different components of the matrix are just beginning to be defined. There appear to be important adaptive responses in the forebrain components of the matrix during arthritic pain. Endogenous opioid peptides are strong candidates for the modulation of some of these responses. More extensive and sequential behavioral and functional imaging studies are required to establish the contribution these adaptive responses make to the perception of pain.

Arthritis, Rheumatoid↗