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Biomedical subjects

A J Shepherd

Publications and source records attributed to A J Shepherd.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1992

Susceptibility of human monoclonal antibody-producing B cell lines to infection by human immunodeficiency virus.

Seven immortalized B cell clones, five of which secreted specific human monoclonal antibodies (MAbs) against hepatitis B, tetanus toxoid, and Rhesus D antigens, were evaluated for their susceptibility to infection by human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2). Infection was confirmed in three human MAb-producing lines by detection of infectious virus and p24 antigen in culture supernates, by immunofluorescence, and by detection of viral DNA in cells by polymerase chain reaction. The infectable lines were as susceptible to HIV-1 infection as several T cell lines and remained persistently infected for several months, but in contrast to T cell controls, viral cytopathic effects were not observed. Levels of unintegrated viral DNA in the HB1 B cell line were significantly lower than in the HUT78 T cell line. Cell lines that were susceptible to HIV expressed HLA DR, CD20, and CD21, whereas the uninfectable cell lines did not express any of the markers tested. CD4 was undetectable or present on a small percentage of cells in two of the infectable cell lines. However, infection with HIV-1 was blocked more efficiently in B cells than in T cells by soluble CD4, anti-CD4 MAb, and dextran sulphate. The effect of HIV infection on human MAb secretion was variable, being reduced on a per-cell basis in one line, increased in another, and unchanged in a third.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1991

Viraemic transmission of Crimean-Congo haemorrhagic fever virus to ticks.

In order to determine the way in which vertebrates infected with Crimean-Congo haemorrhagic fever (CCHF) virus and potential ixodid tick vectors interact in nature, immature and adult ticks of several species were fed on viraemic mammals and then assayed for virus content at varying times after feeding. CCHF virus was not isolated from ticks of six species tested after feeding as adults and immature forms on sheep with viraemia of 10(2.5-3.2) LD 50/ml, nor from larval ticks fed on guinea-pigs and white-tailed rats with viraemia of 10(1.9-2.7) LD 50/ml. In contrast, virus was isolated from 10 of 152 pools of engorged adult ticks of 5 species that fed on cattle with viraemia of 10(1.5-2.7) LD 50/ml and from 3 of 137 female ticks after oviposition. Infection was transmitted to larval and nymphal Hyalomma truncatum and H. marginatum rufipes, but not to Rhipicephalus evertsi evertsi, from a scrub hare with viraemia of 10(4.2) LD 50/ml but only nymphal H. truncatum and H. m. rufipes became infected from scrub hares with viraemia of 10(2.6-2.7) LD 50/ml. Infection was transmitted trans-stadially in H. m. rufipes and H. truncatum infected as nymphae, and adult H. m. rufipes transmitted infection to a sheep. No evidence of transovarial transmission was found in larval progeny of ticks exposed to CCHF virus as adults on sheep and cattle or as immatures on scrub hares.

Animals↗
PubMed1989

Susceptibility of dogs to West Nile virus: a survey and pathogenicity trial.

A serological survey of dogs from the highveld region of South Africa showed that 37 per cent (138 of 377) had neutralizing antibodies to West Nile (WN) virus and only 2.7 per cent (10 of 377) had antibodies to Sindbis virus. WN virus was isolated from one of the WN-antibody negative sera. Because these results suggested that dogs may play an important part in the epidemiology of WN virus, a pathogenicity trial was carried out. Two of three dogs infected with WN virus had a mild recurrent myopathy, but no other abnormalities were detected in the biochemical or haematological tests performed on any of the dogs. All three dogs developed antibodies but a low titre-viraemia was detected in only one dog. It was concluded that dogs do not play an important part in the epidemiology of WN virus but they may play a small part in the maintenance of the virus.

Animals↗
PubMed1989

Experimental studies on the replication and transmission of Crimean-Congo hemorrhagic fever virus in some African tick species.

Seven African tick species were studied as potential vectors of Crimean-Congo hemorrhagic fever (CCHF) virus. Engorged nymphae of 4 ixodid species, Hyalomma marginatum rufipes, H. truncatum, Rhipicephalus evertsi mimeticus, and Amblyomma hebraeum, were inoculated intracoelomically with CCHF virus and assayed for virus content at varying times post-inoculation. The virus replicated in all 4 species, reaching maximum titers of 4.6-5.5(10) fluorescence focus units per ml on days 5-9 post-inoculation. Virus titers declined up to the molt, but increased slightly on emergence of adult ticks. Thereafter, virus titers declined progressively, but infectivity could still be detected in adult ticks for up to 205 days post-inoculation. Groups of H. m. rufipes, H. truncatum, and R.e. mimeticus infected adults were fed on susceptible sheep and successfully transmitted CCHF infection. CCHF virus was not isolated from pools of the larval and nymphal progeny of the female ticks nor did the larvae transmit infection to guinea pigs by bite. CCHF virus failed to replicate in adults and nymphae of 3 argasid tick species, Argas walkerae, Ornithodorus porcinus porcinus, and O. savignyi, after intracoelomic inoculation and could be reisolated from the ticks no later than 1 day post-inoculation. The results suggest that all ixodid ticks are capable of transmitting CCHF virus but argasid ticks do not appear to be capable of serving as vectors.

Animals↗
PubMed1989

Viremia and antibody response of small African and laboratory animals to Crimean-Congo hemorrhagic fever virus infection.

Eleven species of small African wild mammals, laboratory rabbits, guinea pigs, and Syrian hamsters were infected with Crimean-Congo hemorrhagic fever (CCHF) virus. Low-titered viremia followed by development of antibody was observed in scrub hares (Lepus saxatilis), Cape ground squirrels (Xerus inauris), red veld rats (Aethomys chrysophilus), white tailed rats (Mystromys albicaudatus), bushveld gerbils (Tatera leucogaster), striped mice (Rhabdomys pumilio), and guinea pigs. The maximum viremic titer in 4 scrub hares was 10(1.7-4.2) 50% mouse lethal doses/ml. Viremia was detected in 1/17 infected laboratory rabbits. Antibody response was only detected in South African hedgehogs (Atelerix frontalis), highveld gerbils (T. brantsii), Namaqua gerbils (Desmodillus auricularis), 2 species of multimammate mouse (Mastomys natalensis and M. coucha), and Syrian hamsters. The results of the study indicate that a proportion of infected scrub hares develop CCHF viremia of an intensity shown in the Soviet Union to be sufficient for infection of feeding immature ixodid ticks, but that South African hedgehogs and wild rodents are unlikely to be of importance as maintenance hosts of the virus in southern Africa.

Animals↗
PubMed1988

Evaluation of enzyme-linked immunosorbent assay and reversed passive hemagglutination for detection of Crimean-Congo hemorrhagic fever virus antigen.

Enzyme-linked immunosorbent assay (ELISA) and a reversed passive hemagglutination (RPHA) test were evaluated for rapid detection of Crimean-Congo hemorrhagic fever (CCHF) virus antigens. Both RPHA and ELISA detected CCHF antigen in the brains of infant mice 2 to 3 days after infection, several days before the animals sickened and died. Antigen was also detected after 1 to 2 days in infected cell culture extracts and after 2 to 4 days in culture supernatant fluids. Both tests detected CCHF antigen at threshold values of approximately 2.5 log10 tissue culture infective doses per ml and were more sensitive than complement fixation, immunodiffusion, or immunofluorescence. In a comparative study on specimens from CCHF patients, virus was isolated from 38 of 49 sera and 23 of 28 patients. Antigen was detected in 20 of 49 sera (15 of 28 patients) by RPHA and in 29 of 49 sera (18 of 28 patients) by ELISA. Antigenemia was detected more frequently in fatal cases (9 of 11) than in nonfatal cases (9 of 17). Although the antigen detection assays offered a more rapid approach than infectivity assays for diagnosing CCHF, the latter test was more sensitive. The results suggest that RPHA and ELISA may be of use in rapid diagnosis of CCHF infection, particularly in severe cases, in which the danger of nosocomial spread is greatest.

Animals↗
PubMed1987

Field and laboratory investigation of Crimean-Congo haemorrhagic fever virus (Nairovirus, family Bunyaviridae) infection in birds.

In November 1984 a case of Crimean-Congo haemorrhagic fever (CCHF) occurred in a worker who became ill after slaughtering ostriches (Struthio camelus) on a farm near Oudtshoorn in the Cape province of South Africa. The diagnosis was confirmed by isolation of CCHF virus from the patient's serum and by demonstration of a specific antibody response. It was suspected that infection was acquired either by contact with ostrich blood or by inadvertently crushing infected Hyalomma ticks while skinning ostriches. Reversed passive haemagglutination-inhibition antibody to CCHF virus was detected in the sera of 22/92 ostriches from farms in Oudtshoorn district, including 6/9 from the farm where the patient worked, but not in the sera of 460 birds of 37 other species. In pathogenicity studies domestic chickens proved refractory to CCHF infection, but viraemia of low intensity (maximum titre 2.5 log10 mouse ic LD50/ml) followed by a transient antibody response occurred in blue-helmeted guinea fowl (Numidia meleagris). These results offer the first direct evidence that some bird species are susceptible to CCHF virus infection.

Animals↗