PubMed Health⌕ Search

Biomedical subjects

A J Shepherd

Publications and source records attributed to A J Shepherd.

At least 19 recordsLinked to original sources
PubMed2001

VIDA: a virus database system for the organization of animal virus genome open reading frames.

VIDA is a new virus database that organizes open reading frames (ORFs) from partial and complete genomic sequences from animal viruses. Currently VIDA includes all sequences from GenBank for Herpesviridae, Coronaviridae and Arteriviridae. The ORFs are organized into homologous protein families, which are identified on the basis of sequence similarity relationships. Conserved sequence regions of potential functional importance are identified and can be retrieved as sequence alignments. We use a controlled taxonomical and functional classification for all the proteins and protein families in the database. When available, protein structures that are related to the families have also been included. The database is available for online search and sequence information retrieval at http://www.biochem.ucl.ac.uk/bsm/virus_database/ VIDA.html.

Animals↗
PubMed2001

A rapid classification protocol for the CATH Domain Database to support structural genomics.

In order to support the structural genomic initiatives, both by rapidly classifying newly determined structures and by suggesting suitable targets for structure determination, we have recently developed several new protocols for classifying structures in the CATH domain database (http://www.biochem.ucl.ac.uk/bsm/cath). These aim to increase the speed of classification of new structures using fast algorithms for structure comparison (GRATH) and to improve the sensitivity in recognising distant structural relatives by incorporating sequence information from relatives in the genomes (DomainFinder). In order to ensure the integrity of the database given the expected increase in data, the CATH Protein Family Database (CATH-PFDB), which currently includes 25,320 structural domains and a further 160,000 sequence relatives has now been installed in a relational ORACLE database. This was essential for developing more rigorous validation procedures and for allowing efficient querying of the database, particularly for genome analysis. The associated Dictionary of Homologous Superfamilies [Bray,J.E., Todd,A.E., Pearl,F.M.G., Thornton,J.M. and Orengo,C.A. (2000) Protein Eng., 13, 153-165], which provides multiple structural alignments and functional information to assist in assigning new relatives, has also been expanded recently and now includes information for 903 homologous superfamilies. In order to improve coverage of known structures, preliminary classification levels are now provided for new structures at interim stages in the classification protocol. Since a large proportion of new structures can be rapidly classified using profile-based sequence analysis [e.g. PSI-BLAST: Altschul,S.F., Madden,T.L., Schaffer,A.A., Zhang,J., Zhang,Z., Miller,W. and Lipman,D.J. (1997) Nucleic Acids Res., 25, 3389-3402], this provides preliminary classification for easily recognisable homologues, which in the latest release of CATH (version 1.7) represented nearly three-quarters of the non-identical structures.

Computational Biology↗
PubMed2000

Visual contrast processing in migraine.

Some migraine sufferers report certain visual patterns can reliably trigger a migraine attack, such as high contrast striped patterns or flickering lights. Differences between people with and without migraine on tasks that involve these patterns have been attributed to abnormal cortical processing in migraine, although the locus and extent of the abnormality remains unclear, as is any relationship between impairment on various visual tasks. In this study 58 migraine sufferers and 61 control subjects participated in three visual tasks involving striped patterns. One assessed pattern sensitivity with high contrast patterns, the second detection thresholds for low contrast patterns and the third supra-threshold contrast scaling. With each measure, the performance of migraine sufferers as a group differed to the performance of non-migraine control subjects. There were no significant differences between the migraine subgroups when classified according to the presence or absence of aura. Cross-correlating the results from the three tasks, however, revealed consistent associations: impaired or extreme responses on one task were associated with impaired or extreme responses on the others. There were no overall effects due to migraine duration, the frequency of migraine attacks or the time since the last attack. These results are discussed in the context of visually induced migraine, proposed causes of abnormal cortical function in migraine and the prospects for developing clinically useful tests of visual function.

Adolescent↗
PubMed2000

Comparison of an enzyme immunoassay for the detection of Helicobacter pylori antigens in the faeces with the urea breath test.

BACKGROUND: Current diagnostic tests for Helicobacter pylori are invasive (endoscopy) or indirect (urea breath test, serology). AIMS: To evaluate a new enzyme immunoassay (EIA) which detects H pylori antigens in faeces, by comparing its sensitivity and specificity in children with the (13)C urea breath test (UBT). METHODS: A total of 119 children underwent a UBT and provided a faecal sample for antigen testing within seven days. After an overnight fast each child provided a pretest breath sample, and samples at 30 and 40 minutes after ingestion of 100 mg (13)C labelled urea. (13)C enrichment of breath was measured by isotope ratio mass spectrometry. Faeces were stored at -70 degrees C until antigen testing, using the EIA. Samples were read spectrophotometrically at 450 nm and results were interpreted using recommended cut offs of optical density <0.14 as negative, >/=0.16 as positive, with >/=0.14 and <0. 16 representing equivocal results. Sensitivity and specificity were calculated using the manufacturer's cut off compared with UBT. RESULTS: Sensitivity and specificity were 88% and 82%, respectively. Negative and positive predictive values were 97% and 58%. CONCLUSIONS: The EIA is an alternative, non-invasive, and easy to use method for the detection of H pylori in children. Its high negative predictive value suggests a role in screening out uninfected children.

Adolescent↗
PubMed2000

Identification of risk factors in blood donors found to have HIV infection.

To ascertain whether current screening procedures for human immunodeficiency virus (HIV) infected blood can be improved, a study of blood donors found by Mersey and North Wales Blood Centre to be HIV positive was made. In total 22 donors were identified, of which 16 were referred to the Department of Genito-Urinary Medicine (GUM) in Liverpool. Most (9/16) should have been excluded from donating because of recognized risk factors. However, in 7 cases no such identifiable factors were found. Although the risk of transfusion transmitted infection is small, there is an argument for testing donated blood for HIV RNA by nucleic acid technology.

Adult↗
PubMed1999

Remodelling colour contrast: implications for visual processing and colour representation.

Colour contrast describes the influence of one colour on the perception of colours in neighbouring areas. This study addresses two issues: (i) the accurate representation of the colour changes; (ii) the underlying visual mechanisms. Observers viewed a haploscopic display in which a standard display was presented to one eye and a matching display to the other. The matches could be represented accurately using a diagram that is a logarithmic transformation of the MacLeod-Boynton (r, b) (1979) chromaticity diagram. Since haploscopic presentation has been described as isolating retinal processes (Whittle, P., & Challands, P.D.C. (1969). The effect of background luminance on the brightness of flashes. Vision Research, 9, 1095-1110; Chichilnisky, E.J., & Wandell, B.A. (1995). Photoreceptor sensitivity changes explain color appearance shifts induced by large uniform backgrounds in dichoptic matching. Vision Research, 35, 239-254), the results are discussed in terms of receptor sensitivity changes and the ratio of receptor contrasts.

Adult↗
PubMed1999

High throughput detection of retrovirus-associated reverse transcriptase using an improved fluorescent product enhanced reverse transcriptase assay and its comparison to conventional detection methods.

The development and application of a novel, sensitive TaqMan fluorescent probe-based product enhanced RT test (F-PERT) for the detection of retrovirus are described. The assay allows discrimination between the amplification signals generated by genuine positive signals that result from retroviral RT activity and the RT-like activity from DNA polymerases. The RT-like activity from DNA polymerases was suppressed by the addition of activated calf-thymus DNA with no reduction in the RT activity. A linear relationship between threshold cycle (C(T)) and the number of virus particles was demonstrated, allowing quantification of retroviruses in unknown samples. The F-PERT assay was able to detect a wide range of retroviral RT activities, including that from porcine endogenous retrovirus (PoERV), murine leukaemia virus (MLV), simian foamy virus (SFV), simian immunodeficiency virus (SIVmac) and squirrel monkey retrovirus (SMRV). The detection limit of SMRV, MLV and PoERV was approximately 100 virion particles and the test was able to detect at least 10(2) molecules of purified RT enzyme. RT activity was not detected in cellular lysates and supernatants from MRC-5, BT, VERO, or Raji cells, whereas RT activity was detected in C1271, Mus dunni, K-Balb, BHK-21, CHO-K1, SP2/0-Ag14 and NSO cell supernatants. RT activity was also detected in the Spodoptera cell line Sf9.

Animals↗
PubMed1999

Prognostic value of flash visual evoked potentials in preterm infants.

This paper investigates the prognostic value of flash visual evoked potentials (VEPs) recorded in preterm infants at birth and at term age with respect to severe neurological outcome. Flash VEPs were recorded in 81 preterm infants at birth (i.e. <35 weeks' gestation) and repeated in 56 of these infants at term age. The preterm infants were assigned to either a healthy or at-risk subgroup based on clinical birth factors. Normal ranges of flash-VEP latencies, amplitudes, and number of components present were obtained from the subgroup of healthy preterm infants and from 68 term infants tested postnatally. The flash-VEP results of the entire preterm group were compared with the normal ranges and any abnormalities noted. Seven preterm infants in the at-risk group died, six of whom had abnormal flash VEPs before term age. Of the five infants from the at-risk group diagnosed with cerebral palsy (CP), three had abnormal flash VEPs before term age. Thus the sensitivity and specificity of the flash VEP with respect to survival was 86% and 89% respectively, and with respect to the development of CP was 60% and 92%. The abnormal features of the flash VEP associated with adverse outcomes comprised a delayed N3 component before term age and the absence of a positive component (P2) at term age.

Cerebral Palsy↗
PubMed1999

Prediction of the location and type of beta-turns in proteins using neural networks.

A neural network has been used to predict both the location and the type of beta-turns in a set of 300 nonhomologous protein domains. A substantial improvement in prediction accuracy compared with previous methods has been achieved by incorporating secondary structure information in the input data. The total percentage of residues correctly classified as beta-turn or not-beta-turn is around 75% with predicted secondary structure information. More significantly, the method gives a Matthews correlation coefficient (MCC) of around 0.35, compared with a typical MCC of around 0.20 using other beta-turn prediction methods. Our method also distinguishes the two most numerous and well-defined types of beta-turn, types I and II, with a significant level of accuracy (MCCs 0.22 and 0.26, respectively).

Algorithms↗
PubMed1997

A vector model of colour contrast in a cone-excitation colour space.

A vector model of colour contrast is examined in a colour space that is a logarithmic transformation of the MacLeod-Boynton cone-excitation diagram. Observers set matches in a haploscopic display, in which one eye viewed a standard display (a neutral target square in a coloured surround) and the other viewed a matching display (a variable square in its own surround). Contrast colours are simply represented in this colour space: the vector connecting the right-eye surround and matched chromaticities is parallel to and to the same length and direction as the vector that connects the left-eye (standard) surround and square chromaticities. This describes observers' matches to the hues induced in a neutral square for a range of inducing surround colours, a range of right-eye (match) surround colours and four different luminance contrasts.

Adult↗
PubMed1997

Calibrating screens for continuous colour displays.

This paper focuses on two issues that are important to those who use colour monitors for research in vision. One is concerned with the measurement and calibration of colour screens. To this end the luminance and chromaticity readings of a tri-filter colorimeter and a spectroradiometer are compared (both commonly used to calibrate screens). The second is concerned with screen interactions, whereby colours can be distorted from their expected or calculated values by the colours displayed in neighbouring areas. This issue is crucial for those who use measurements of the light emitted from the red, green and blue phosphors of a monitor in isolation to specify other colours on screen, particularly in the research areas of colour contrast and colour constancy, since the specified colours may not actually be displayed. Finally, an alternative calibration method is described that uses an iterative measurement procedure to obtain screen specifications that are accurate regardless of the display complexity, so that researchers can be confident that the required colours are actually displayed on the screen.

Calibration↗
PubMed1996

Detection of unintegrated HIV type 1 DNA in cell culture and clinical peripheral blood mononuclear cell samples: correlation to disease stage.

This article reports on the development of PCR as a sensitive method of detecting both linear and circular forms of HIV-1 unintegrated viral DNA (UVD). The method was developed in a cell line study designed to follow the sequential synthesis of these forms over time. In all T lymphoid lineage cell lines, the full-length linear UVD (LUVD) was synthesized prior to both 1 and 2 LTR forms of circular UVD (CUVD), although all forms were detected by 12 hr postinoculation. Analysis of unstimulated PBMC samples from HIV-positive patients showed a significant difference in the presence of detectable CUVD forms and CDC groups II and IV (p < 0.001) and CDC groups III and IV (p < 0.001). No significance was demonstrated between CDC groups II and III (p > 0.5), linking the presence of CUVD forms to clinical disease and immunodeficiency. We propose that circular unintegrated forms of HIV-1 DNA may play a role in the development of acquired immunodeficiency syndrome.

Adult↗
PubMed1996

Gene delivery systems for use in gene therapy: an overview of quality assurance and safety issues.

The development of safe and effective agents for gene therapy is founded on three main principles; careful choice and design of vectors, assessment of vector safety under GLP and production of the vector stocks under GMP. The first ensures the safe and appropriate contained delivery and expression of the required gene to the recipient of the therapy. GLP provides fully documented studies of potency, efficacy and safety of the product while the production of clinical grade agents under GMP is essential.

Genetic Therapy↗
PubMed1992

Coloured shadows described in a cone contrast space.

Two effects which can modify the appearance of a colour seen in a context compared to isolation are chromatic induction and colour constancy. These effects transform colour in ways which depend on the visual system rather than physical characteristics of light and surfaces. They need not reflect different processes within the visual system, indeed, chromatic induction has been attributed to the same processes as those involved in constancy, or, as an error of the visual system attempting to achieve constancy. This hierarchy is not necessary: both constancy and induction may result from the same processes without requiring that one promotes the other or that constancy is a goal of the visual system. This study examines induction in terms of cone contrasts in a coloured shadow display, part of a study to establish a relevant measure of contrast and its role in chromatic induction and colour constancy.

Color Perception↗
PubMed1992

The effect of thymidine on the antibacterial and antiviral activity of zidovudine.

The effect of thymidine and deoxyadenosine on the antiviral and antibacterial effect of zidovudine was studied in human immunodeficiency virus type 1 (HIV-1) Escherichia coli and Salmonella typhimurium. In quantitative assays, 10 micrograms mL-1 thymidine was shown to increase the 50% inhibitory concentration (IC50) of zidovudine for HIV-1 by approximately 100-fold and to reduce zidovudine (1 microM)-induced protection of C8166 cells from 2.04 to 0.18 log syncytial-forming units. Thymidine also antagonized the antibacterial effect of zidovudine for two E. coli and three S. typhimurium species in a dose-dependent manner; 10 micrograms mL-1 of thymidine increased the minimum inhibitory concentration of zidovudine for E. coli strains by 10-40-fold and for S. typhimurium strains by three-fold. Deoxyadenosine reduced the minimum inhibitory concentration of zidovudine against all five bacterial strains but had no effect on the IC50 of zidovudine for HIV-1, nor did it significantly reverse the antagonism of the antibacterial and antiviral activity of thymidine. The induction of the SOS response in E. coli was reversed in a dose-dependent manner by thymidine while the presence of deoxyadenosine increased induction of the SOS response by zidovudine at suboptimal concentrations.

Deoxyadenosines↗