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Biomedical subjects

G R Skinner

Publications and source records attributed to G R Skinner.

At least 37 records · Page 2Linked to original sources

The effects of lithium and potassium on macromolecular synthesis in herpes simplex virus-infected cells.

All herpes simplex virus (HSV) infected cell-specific polypeptides (ICSPs) were synthesized in the presence of lithium at a concentration (60 mM) inhibitory to the production of infectious virus. Yields of certain ICSPs were increased and others, in particular glycoprotein C, decreased. HSV DNA synthesis was completely inhibited; synthesis and in vitro activities of HSV DNA polymerase and thymidine kinase were decreased but to a degree insufficient to account for the complete inhibition of HSV DNA synthesis. HSV DNA synthesis was inhibited to an equivalent degree by either incubation with 60 mM-lithium or by potassium starvation; both procedures decreased intracellular potassium by an equivalent amount as adjudged by X-ray microanalysis. We conclude that lithium inhibits HSV DNA synthesis by displacement of potassium from a potassium-dependent biochemical reaction or by other physiological changes brought about by the loss of cellular potassium. The possibility that lithium also directly inhibits a virus replicative event cannot be excluded.

Animals↗

Development of subunit preparations of cytomegalovirus antigen by aqueous extraction for immunization against cytomegalovirus infection.

This study has examined different methods of preparation of a subunit vaccine from cytomegalovirus (CMV)-infected MRC cells in terms of protein and DNA content, antigenicity and immunogenicity. Two preparations have been developed where CMV proteins were obtained by extraction of infected cells with water. Virus particles were removed from the preparations by ultracentrifugation and residual virus was inactivated by formaldehyde in the WUF preparations or by chloroform in the WUCh preparations. The preparations contained CMV proteins which may play a role in protective immune responses, and the preparations were antigenic as determined by immunodiffusion, ELISA and immunoblotting. Immunogenicity as evaluated in rabbits indicated that the preparations stimulated neutralizing and immunoprecipitating antibody. These results suggest that the gentle method of water extraction of viral antigens may be a useful protocol for vaccine preparation.

Animals↗

Report of twelve years experience in open study of Skinner herpes simplex vaccine towards prevention of herpes genitalis.

Three hundred and forty-seven subjects at risk for herpes genitalis were vaccinated with Skinner vaccine, NFUAc.HSV1.(S-MRC5), and were followed for an average duration of 2 years representing a total consortship of 664.4 years. Based on survey information obtained during this consortship, there were estimated to be 3076 recurrences which summated to 3.5 years total duration of disease and comprised at least 6794 lesions; there were an estimated 51997 episodes of intercourse including at least 241 episodes of unprotected intercourse in the presence of herpetic lesions. The rate of contraction of herpes genitalis was 6 of 54 consorts (11.1%) who received one vaccination and 7 of 293 (2.4%) who received two, three of four vaccinations. There was no evidence of physical or psychological side effects from vaccination.

Adolescent↗

In vivo model for evaluation of species-specific virus vaccines.

It is difficult to evaluate the protective efficacy of species-specific viruses of humans and expensive companion animals where there is no non-human animal model. This study describes an in vivo model system which allows simultaneous operation of humoral, cell-mediated, interferon-like or other unidentified immunological defence mechanisms. There was evidence of in vivo inactivation of both enveloped and unenveloped DNA and RNA viruses including retrovirus mouse sarcoma virus/mouse leukaemia virus as evaluated by assay of the enzyme reverse transcriptase. This model will allow examination of vaccine efficacy in immunocompetent host animals while avoiding morbidity and/or mortality from virus infection in these animals.

Animals↗

Glycoprotein patterns in normal and malignant cervical tissue.

Glycoproteins from normal and malignant human cervix were studied using an organ culture system and compared by gel electrophoresis and autoradiography. Five glycoproteins of 178 kDa, 95 kDa, 93 kDa, 82 kDa and 38 kDa and 1 glycolipid (46 kDa) were detected more frequently in squamous carcinomas. Certain glycoproteins were shown to be oncofoetal and some had affinity for Concanavalin A (Con A). The 82 kDa glycoprotein was present in 16/17 squamous carcinomas but in only 1/13 normal cervices. This band represented a glycoprotein containing glucosamine, mannose, small quantities of methionine and no fucose. These preliminary results suggest that these glycoproteins and in particular the 82-kDa glycoprotein are worthy of further investigation and characterisation.

Adenocarcinoma↗

A virus-particle vaccine prepared from bovine mammillitis virus against herpes genitalis.

A vaccine against herpes genitalis was prepared from the extracellular virus particles from baby hamster kidney cells infected with bovine mammillitis virus (BMV) strain "Allerton". The virus was inactivated by formaldehyde followed by ultracentrifugation to concentrate the virus particles and eliminate formaldehyde to an acceptable concentration for immunisation of human subjects. The vaccine was cross antigenic and cross immunogenic with herpes simplex virus type 1. Thirty-four consorts at high risk of herpes genitalis were immunised with two or three doses each containing 10(9) virus particles equialent to approx. 150 micrograms protein. There has been no evidence of local or general side effect in a follow-up period of over 100 patient years. The immunogenicity and protective efficacy of this vaccine in human subjects will be investigated in a double-blind placebo-controlled trial.

Adult↗

Immune inhibition of virus release from human and nonhuman cells by antibody to viral and host cell determinants.

Immune inhibition of release of the DNA viruses, herpes simplex virus types 1 and 2 and pseudorabies virus by anti-viral and anti-host cell sera occurred while two RNA viruses, influenza and encephalomyocarditis, were inhibited only by anti-viral sera (not anti-host cell sera). Simian virus 40 and surprisingly two herpes viruses, bovine mamillitis and equine abortion, were not inhibited by either anti-viral or anti-host sera. Using the herpes simplex virus model, inhibition of virus release was detected in different cells of human and nonhuman origin with cross-inhibition between cell lines of different origin; thus, this form of immunotherapy may not require antibody to be tissue or organ specific. Evidence of inhibition of virus release from neoplastic and leukemic cell lines suggests possible application of this approach to control of virus-mediated leukoproliferative pathology (e.g. Burkitt's lymphoma or adult T cell leukemia).

Animals↗

Inhibition of rate of tumour growth in rodent species by inoculation of herpesviruses and encephalomyocarditis virus.

Inoculation of herpesviruses and encephalomyocarditis virus into subcutaneous tumours in hamsters and mice reduced the rate of tumour growth compared to untreated tumours or secondary tumours which had arisen following surgical excision of the primary tumour; in addition, survival times were increased in animals whose tumours were inoculated with virus. It is suggested that the role of virus in the modification of tumour growth merits further exploration.

Animals↗

Sequential release of antigens from chloroform-treated Staphylococcus epidermidis: application towards a possible vaccine.

This study describes the properties of two potential Staphylococcus epidermidis vaccines prepared by chloroform treatment of bacteria and release of antigen from these chloroform-treated organisms. Both vaccines were antigenic on testing with homologous hyperimmune serum and induced immune reactivity in immunized rabbits. There was protective efficacy in mice against intraperitoneal challenge by Staph. epidermidis.

Animals↗

Humoral antibody response in patients with herpes genitalis: analysis of factors influencing the pattern of disease.

An investigation was made of the diagnosis of herpes genitalis, the prediction of virus type and the likelihood and frequency of clinical and asymptomatic recurrences in relation to a history of herpes labialis, the virus type isolated from genital lesions and the humoral antibody status against HSV 1 and 2. Diagnosis of herpes genitalis correlated negatively with mean neutralising antibody levels against HSV type 1 and type 2 but positively with the variance of neutralising antibody levels in sequential sera. Virus type in patients with initial episodes was best predicted by initial and mean type 2 antibody levels and in patients with recurrent disease by the ratio of type 1 to type 2 antibody by radioimmune assay. The likelihood and frequency of clinical and asymptomatic recurrences was higher in patients where HSV type 2 was isolated. The likelihood of recurrences in patients with initial episodes was related to high initial neutralising antibody levels against type 2 and to low primary antibody responses against type 1 while frequency of recurrences was best related to low initial antibody levels against type 1 in combination with high levels against type 2. These data will be useful in diagnosis of herpes genitalis. Prediction of the likelihood and frequency of clinical and asymptomatic recurrences will facilitate advice concerning prognosis and risk factors to patients and their consorts.

Animals↗

The immunological relationship between canine herpesvirus and four other herpesviruses.

Canine herpesvirus (CHV) was compared with four other herpesviruses by several serological techniques. Cross-neutralization was demonstrated between CHV and herpes simplex virus types 1 and 2 and pseudorabies virus. Non-neutralizing cross-reactions were found with these viruses and also with equine abortion virus and bovine mammillitis virus. The data suggest that CHV is immunologically more closely related to herpes simplex virus than to the other viruses used in this study.

Antibodies, Viral↗

Immune inhibition of virus release from herpes simplex virus-infected cells by human sera.

Human sera contain antibody (IVR antibody) which will inhibit the release of herpes simplex virus type 1 from virus-infected cells. This antibody activity was removed by adsorption of sera with virus-infected cell extract. There was a positive correlation between IVR and neutralizing antibody activity, particularly when measured by augmented neutralization test; measurement of IVR antibody was equally as sensitive as measurement of neutralizing antibody by augmented neutralization test. IVR antibody levels provided indication of a history of recurrent herpes labialis, the pattern of antibody response following primary herpetic infection, and indication of response to Skinner herpes vaccine in human subjects. It is suggested that consideration should be given to measurement of IVR antibody in both clinical and epidemiological studies of herpes and other virus infections.

Antibodies, Viral↗

Reduced tumorigenicity of rodent tumour cells and tumour explants following infection with wild type and mutant herpes simplex virus, bovine mammillitis virus and encephalomyocarditis virus.

The tumorigenicity of neoplastic hamster and mouse cell lines and tumour explants was reduced by infection with herpes simplex virus (HSV-1), a thymidine-kinaseless mutant of herpes simplex virus, namely 'MDK', encephalomyocarditis virus (EMC) and bovine mammillitis virus (BMV). There was an approximate relationship between duration of virus infection in vitro and reduction in incidence and/or rate of tumour development. The rate of tumour development was also reduced by 'site inoculation' of virus (HSV-1) at various time intervals following inoculation of tumorigenic BHK 21 cells indicating that virus was capable of reducing the rate of tumour development in a situation where the neoplastic cells were already transplanted into the susceptible host species. It is suggested that the therapeutic role of wild type, mutant or recombinant viruses merits further exploration towards prevention and treatment of human cancer.

Animals↗

Cervical carcinoma: an experimental approach.

A mouse model system was used to investigate the preventive efficacy of a subunit herpes simplex virus (HSV) vaccine on the development of HSV induced cervical carcinoma. Ten groups of mice were vaccinated before receiving repeated intravaginal exposure to HSV-type 2 inactivated by ultraviolet irradiation. At 20 months postvaccination, neutralizing antibody activity to herpes simplex viruses was detected in the sera of the mice which had received the highest vaccine dose. Although three experimental mice and one control mouse developed cervical tumours and five mice developed preinvasive malignant changes, 87% of cervices were of normal or koilocytotic appearance on histological examination. There was therefore no evidence from this study that repeated exposure of mouse cervices to inactivated HSV-2 induced a significant incidence of preinvasive or invasive cervical carcinoma.

Animals↗

Follow-up report on 50 subjects vaccinated against herpes genitalis with Skinner vaccine.

Fifty subjects at risk of herpes genitalis received 109 immunizations with Skinner herpes vaccine and were assessed after a follow-up period of 4-48 months, representing a total follow-up period of 694 patient months. There was no evidence of contraction of herpes genitalis in 49 subjects. The risk of virus transmission and rate of contraction of disease was quantified by construction of two functions, namely a unit of exposure risk calculated per year (UYE) and standard contraction rate (SCR); in this study the SCR was 0.02. There was no evidence of significant side-effects from vaccination. Administration of Alhydrogel adjuvant with vaccine induced temporary granuloma formation in most subjects but was only detectable beyond 1 year of follow-up in one subject, in whom a painless swelling of 0.2 cm was detected 3 years after vaccination. There was no evidence of immunological reactivity to host cell or calf serum antigens in any of the subjects vaccinated.

Adolescent↗