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Biomedical subjects

G R Skinner

Publications and source records attributed to G R Skinner.

At least 19 recordsLinked to original sources
PubMed2001

The infrequency of transmission of herpesviruses between humans and animals; postulation of an unrecognised protective host mechanism.

The infrequency of natural transmission of herpesviruses between humans and animals is surprising as there is extensive contact between humans and non-human species with unequivocal evidence that host cells from non-susceptible species will support replication of herpesviruses which do not seem to naturally infect that species. This review examines natural cross-infections between human and other species and suggests that, firstly, it is possible that humans and animals do become asymptomatically or symptomatically cross-infected from other species, but the infection is not diagnosed or not diagnosable by conventional methods; secondly, an as yet unidentified novel mechanism(s) may operate to prevent infection using chemical, electrical or as yet unidentified pathways and may even be 'switched on' by exposure to the virus.

Animals↗
PubMed2000

Reduced hepatic content of dehydroepiandrosterone sulphotransferase in chronic liver diseases.

AIMS/BACKGROUND: Dehydroepiandrosterone sulphotransferase (DHEA ST) is the enzyme responsible for sulphation of lithocholic acid and other potentially hepatotoxic steroids. We have previously shown that DHEA ST activity is reduced in cytosol of liver from miscellaneous patients with chronic liver disease. The aim of this study was to investigate the cause of diminished sulphotransferase activity in order to further our understanding of whether a reduction in the ability to sulphate potentially hepatotoxic bile acids might play a role in the aetiology of primary cholestatic liver disease. METHODS: We quantified DHEA ST in human liver cytosol from groups of patients with chronic liver diseases and normal subjects using a semiquantitative sodium dodecyl sulphate/polyacrylamide gel electrophoresis (SDS-PAGE)/ immunoblotting method, and an enzyme-linked immunosorbent assay (ELISA). We determined DHEA ST enzyme activity and correlated it with its immunoreactive concentration in 87 samples of human liver tissue. RESULTS: DHEA ST activity and concentration were significantly reduced in primary biliary cirrhosis, primary sclerosing cholangitis, chronic active hepatitis and alcoholic cirrhosis but not in cryptogenic cirrhosis when compared to normal liver. There were no significant differences among disease groups. In all groups enzyme activity and cellular concentration correlated, suggesting that no aberrant non-functional enzyme was produced. CONCLUSION: These results confirm that DHEA ST activity is diminished in liver disease and that the reduction is due to diminished enzyme presence. Further studies are required to show whether the reduction has any pathogenetic significance or is merely a consequence of disease.

Adult↗
PubMed2000

Efficacy of an inactivated vaccine for equine herpesvirus type 1 in a novel hamster model.

A vaccine designated F.EHV1(S(-))BHK, which was prepared by formaldehyde treatment of equine herpesvirus type 1 (EHV1)-infected baby hamster kidney cells, stimulated neutralising antibodies in hamsters and rabbits and protected new-born hamsters against a lethal challenge with EHV1 by vaccination of their pregnant mothers. The preparative method was then modified to eliminate virus particles and intraparticulate DNA, producing a vaccine designated Bg.F.EHV1(S(-))BHK. this modification stimulated neutralising antibodies with evidence of in vivo inactivation of the virus above non-specific levels in a mouse model. There were no adverse effects from these vaccines in rodent or rabbit species.

Animals↗
PubMed2000

Prevention of herpes genitalis by the 'Bulgarian' vaccine F.HSV-2V(PRK): preliminary clinical evidence.

AIM: To examine the antigenic properties of the formalin-inactivated herpes simplex virus type 2 (HSV-2) virus-particle vaccine F. HSV-2V(PRK), which has been used therapeutically in Bulgaria for 30 years, and to make preliminary assessment of its potential protective efficacy by a follow-up of vaccinated patients with herpes genitalis. METHODS: Properties of the vaccine were examined by standard immunological laboratory tests. Fifty-five patients at risk of herpes genitalis received 2-4 vaccinations and were monitored during a 6-year follow-up. RESULTS: The vaccine was antigenic in laboratory tests and absorbed neutralizing antibody from hyperimmune rabbit serum against herpes simplex virus type 1 (HSV-1). In vaccinated patients, there was an overall contraction rate of herpes genitalis of 5.4%. There was no evidence of significant local or generalized adverse effects from vaccination. CONCLUSION: Bulgarian vaccine F.HSV-2V(PRK) may have protective efficacy, which, in association with its apparent safety from our findings and from its clinical use for over 30 years in Bulgaria, suggests that it should be scrutinized by a formal clinical trial.

Adolescent↗
PubMed1998

The influence of the milieu on the rate of neutralisation of herpes simplex virus 1.

The rate of neutralisation of herpes simplex virus 1 was increased by up to more than five hundred-fold when the virus suspension and antiserum were each diluted to one hundred-fold in water instead of phosphate buffered saline. This phenomenon, which was observed for two human positive sera and a rabbit purified polyclonal antibody, may represent an unrecognised homeostatic mechanism where neutralising antibody is 'dilution-fast' under physiological conditions of transudation or pathological conditions of inflammation.

Animals↗
PubMed1998

Environmental influence on immune inhibition of release of herpes simplex virus from cells.

Immune inhibition of virus release (IVR) of herpes simplex virus type 1 (HSV-1) from baby hamster kidney cells (BHK-21) was mediated by antisera against BHK cells, HSV-1, human fibronectin and mouse heparan sulphate proteoglycan and was irreversible for at least 24 h following removal of antiserum. Enhancement of IVR by calf serum depletion of growth media was obtained in varying measure using each of these antisera and also by treatment of virus-infected cells by the lectin concanavalin A. Enhancement was reversible by replenishment of growth media with bovine serum components larger than 12 kD but this only occurred when replenishment was instituted prior to virus infection. There was also reversibility to varying degree following replenishment by ovine, equine and human serum which indicates that this phenomenon is not species specific. In addition to the presence of relevant antigens on the cell surface, IVR may also require an alteration in the cell membrane; this is evidenced by the absence of anticellular serum-mediated IVR when treatment was introduced less than 6 h after virus infection, suggesting that a certain level of alteration or possibly cell damage - in this case virus induced - is necessary. Enhancement of IVR by calf serum depletion would seem to operate through a specific alteration in the virus-infected cell membrane as serum-depleted cells did not show histological alteration and were able to replicate HSV-1 to usual titres; it is possible that this enhancement may represent an as yet unidentified host defence mechanism whereby extracellular release of virus will be reduced in ischaemic or necrotic tissue in the course of infectious inflammatory processes.

Animals↗
PubMed1998

Antiviral efficacy of disinfectant solution MRI-1.

Disinfectant MRI-1 was prepared by dissolution of non-ionic and ionic detergent in ethanol. The disinfectant inactivated extracellular and intracellular enveloped and non-enveloped viruses including herpes viruses, influenza A and human immunodeficiency disease virus in suspension or on surfaces by pre-exposure or post-exposure to the disinfectant; in addition, cells were disabled as potential hosts for viral infection using concentrations of MRI-1 which were 50-fold less than the operative concentration for disinfection. There was no evidence of in vitro mutagenicity using Salmonella typhimurium or sensitization or other adverse effect in a guinea pig model or in human subjects.

Animals↗
PubMed1997

The efficacy and safety of Skinner herpes simplex vaccine towards modulation of herpes genitalis; report of a prospective double-blind placebo-controlled trial.

A randomised, placebo-controlled, multi-centre trial of intracellular subunit herpes simplex virus (HSV) type 1 vaccine NFU.Ac.HSV-1(S-)MRC (Skinner vaccine) was conducted at three medical centres in the United States. Subjects with documented herpes genitalis of at least 1-year duration and a history of six or more genital HSV recurrences in the 12 months prior to study entry were randomised to receive vaccine or placebo at 0, 1 and 2 months. Vaccination induced significant neutralising, enzyme-linked immunosorbent assay and lymphocyte transformation response to HSV-1 antigen. The frequency of recurrences was reduced in the vaccinated female patients at both 3 and 6 months following vaccination with an overall reduction in patients of both sexes which did not reach statistical significance. Recurrence severity was reduced as measured by decreased number of lesions and associated symptoms per recurrence (P = 0.04). The data suggest that clinical manifestations of latent HSV genital infection may be modified by therapeutic immunisation.

Adult↗
PubMed1997

A system for isolation, transport and storage of herpes simplex viruses.

A major difficulty with diagnostic virus isolation concerns the relative thermolability of certain viruses, e.g. herpes simplex virus type 2, which may, therefore, lose infectivity during transport to the laboratory. This study describes a system of virus isolation and transport, which depends on direct inoculation at the bedside or clinic, to a monolayer or suspension of susceptible cells with subsequent incubation for 10 h at approximately 32 degrees C, whereupon the newly synthesised virus becomes very stable if the cells are subsequently maintained at room temperature. This system was found to increase the sensitivity of isolation of herpes simplex virus, particularly under conditions of asymptomatic virus excretion or if there was significant delay in transportation of clinical samples to the virus laboratory. It is envisaged that this system will allow clinical self-sampling by the patient with application to epidemiological surveys in both the developed and underdeveloped world.

Animals↗
PubMed1996

Antiviral properties of extract of Opuntia streptacantha.

An extract of the cactus plant Opuntia streptacantha inhibited intracellular virus replication and inactivated extracellular virus. Inhibition of virus replication also occurred following pre-infection treatment--a favourable finding in terms of in-vivo limitation of virus disease. There was inhibition of both DNA and RNA virus replication, for example, herpes simplex virus, equine herpes virus, pseudorabies virus, influenza virus, respiratory syncytial virus and human immunodeficiency virus, with normal protein synthesis in uninfected cells at extract concentrations which were 15-fold in excess of 50% viral inhibitory concentrations (1 mg/ml). The active inhibitory component(s) of the extract appeared to be protein in nature and resided mainly in the wall of the plant rather than in the cuticle or inner sap. The extract was non-toxic on oral administration to mice, horses and human patients; the non-toxicity of intravenous administration of 70 mg to a mouse representing at least fifty tissue culture 50% viral inhibitory dosages encourages clinical trial of this extract in virus disease of human and veterinary species.

Animals↗
PubMed1996

An outbreak of herpes rugbiorum managed by vaccination of players and sociosexual contacts.

An outbreak of herpes rugbiorum involved nine players including the scrum half and the full back. The infection was characterized by significant constitutional upset with decreased levels of general fitness and match performance for 1-4 months following the outbreak; one player had herpetic lesions on his right eyelid and corneum. Every infected player, 15 non-infected players and five sociosexual contacts received two vaccinations with intracellular subunit vaccine NFU. Ac. HSV-1 (S-MRC5). None of the players or contacts developed cutaneous herpetic recurrence during a follow-up period of 3 years; the player with ocular disease had one recurrence at 30 months following the original episode. These findings encourage consideration of prophylactic or post-exposure vaccination of participants in rugby or other contact sports with this or other appropriate herpes simplex vaccine.

Adolescent↗
PubMed1996

Growth of herpes simplex type 1 on skin explants of atopic eczema.

In a novel approach to looking at why some children with atopic eczema are susceptible to cutaneous herpes simplex virus (HSV) infections, this study evaluates the hypothesis that HSV replicates more easily on eczematous than normal skin. Growth of HSV on eczematous skin explants was compared with growth on explants from three control groups (psoriasis, Darier's disease and normal skin) over a 2-day period. Growth of HSV was significantly less on normal skin than in atopic eczema, psoriasis and Darier's disease. Virus replicated more quickly, and grew to higher titre within 24h, in eczematous and psoriatic explants than in normal skin. A defect in skin barrier function and host defence factors including local cytokine secretion are discussed as possible mechanisms in causing the increased susceptibility of children with atopic eczema to HSV infection.

Adolescent↗
PubMed1996

Immunological studies of herpes simplex virus infection in children with atopic eczema.

This study examines the role of immune defence mechanisms in herpes simplex virus (HSV) infections in atopic eczema and whether impairment of these mechanisms explains the susceptibility of some children with atopic eczema to cutaneous HSV infections. Ten children with eczema herpeticum and 13 with atopic eczema and recurrent HSV infection affecting multiple skin sites were studied, together with relevant control groups. In all children with atopic eczema, in vitro lymphoproliferation in response to stimulation with concanavalin A (Con A) was significantly decreased and natural killer (NK) cells (CD16 + 56) were reduced compared with non-atopic controls. IL-2 receptors, a marker for lymphocyte activation, were decreased during the acute phase of eczema herpeticum, and for 1 month thereafter. A positive stimulation index (> 3) to HSV antigen, and high HSV IgG antibody titres measured by ELISA, Western blotting and neutralization assay, were seen in children with eczema herpeticum by 6 weeks, and also in children with atopic eczema and recurrent HSV infections. No evidence of an HSV-specific immune defect (either cell-mediated or humoral) was found in atopic eczema. Impairment of cell-mediated immunity in atopic eczema was suggested by the reduced response to Con A. It is likely that reduced numbers of circulating NK cells and a decrease in IL-2 receptors during early eczema herpeticum contribute to the susceptibility of children with atopic eczema to cutaneous HSV infections.

Acute Disease↗
PubMed1994

Characterization and immunogenicity of a candidate subunit vaccine against varicella-zoster virus.

This study describes the properties of an inactivated subunit antigen preparation from varicella-zoster virus (VZV)-infected MRC-5 cells by treatment with detergent and formaldehyde, ultracentrifugation over sucrose and acetone precipitation. The method preserved the antigenicity of VZV proteins and several VZV-specific glycoproteins, while virus DNA was less than 20 pg/250 micrograms protein--a putative vaccine dose. The vaccine was immunogenic in rabbits and stimulated antibodies to the major capsid protein as well as to glycoproteins; an immunoprecipitin was shared with a known immune human serum. The preparation contained no infectious VZV with no evidence of side effects in a rabbit or in five human vaccinees during a follow-up period of 6-10 years.

Aged↗
PubMed1994

Early studies on a candidate intracellular subunit vaccine NFU.Ac.HIV[JM] for prevention and/or modification of HIV-related disease.

A candidate HIV subunit vaccine NFU.Ac.HIV[JM] was prepared by detergent and formaldehyde treatment of HIV-infected JM cells. The preparation contained HIV polypeptides at 200, 118, 70, 41 and 24 kD, with reactivity by immunoblotting of approximately fifteen virus-specific polypeptides including polypeptides at 119, 55, 41 and 24 kD, which may represent gp 120, p55, gp41 and p24, respectively. The content of gp120 was estimated to be 5 micrograms/ml. The vaccine was immunogenic in a rabbit, inducing neutralising antibody and reactivity by ELISA and by immunoblotting against a number of HIV polypeptides including those of molecular weights 24, 41, 55 nd 120 kD. The vaccine contained no infectious HIV or reverse transcriptase enzyme activity.

AIDS Vaccines↗