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Biomedical subjects

H E Webb

Publications and source records attributed to H E Webb.

At least 37 records · Page 2Linked to original sources
PubMed1987

Semliki Forest virus induced, immune mediated demyelination: the effect of irradiation.

Intraperitoneal infection with the avirulent A7(74) strain of the alphavirus Semliki Forest virus (SFV) induces an immune mediated demyelinating encephalomyelitis. The blood and brain virus titres, the serum antibody titres and the histopathological changes in the brains of normal mice and mice immunosuppressed with 5.0 or 8.0 Gy total body irradiation (TBX) were determined. SFV infection of immunosuppressed mice resulted in persistently high blood and brain virus titres, neuronal pycnosis, paralysis and death. No demyelination or central nervous system (CNS) inflammatory response occurred in these immunosuppressed mice despite high and persistent brain virus titres. The CNS inflammatory response and associated demyelination could be restored to infected immunosuppressed mice by adoptive transfer of spleen cells, and these changes were brought forward if the donor spleen cells were from mice previously sensitized to SFV. The results indicate that the immune response following SFV A7(74) infection is both protective and pathogenic, and that the demyelination is immune mediated and does not result from direct viral destruction of oligodendrocytes, or any other direct effect of the virus.

Animals↗
PubMed1987

The effect of cycloleucine on SFV A7(74) infection in mice.

Cycloleucine (CL), a non-metabolizable amino acid analogue, was found to reduce thymus and spleen weights in Semliki Forest virus (SFV) strain A7(74) infected and control mice. The maximum effects were seen when three daily doses of CL were given to mice 24 h after an SFV A7(74) infection. In these mice thymus atrophy led to abolition of thymus dependent immune responses and changes in the pathological features of the viral infection--the most striking feature being prevention of demyelination. In addition virus titres in the brains of CL treated infected mice were increased and prolonged. These results show that demyelination following an SFV A7(74) infection is not a result of direct virus action, but of a T-cell mediated mechanism.

Amino Acids↗
PubMed1986

Use of N-acetylethyleneimine [AEI] for the inactivation of Semliki Forest virus in vitro.

N-Acetylethyleneimine (AEI) was used to inactivate the avirulent Togavirus Semliki Forest virus (A774 strain) grown in chick embryo, Vero, and brain cell cultures. The purity of the virus preparation affected the kinetics of inactivation. The rate of inactivation increased with a rise in temperature from 5 to 40 degrees C and in concentration of AEI from 0.025 to 0.1%. The resultant vaccine was inoculated into adult mice to test its antigenicity and into suckling mice to test for the presence of infective virus. Semliki Forest virus-specific IgG was produced equal to that of mice given live virus, and mice were protected against the lethal SFV L10 strain. No suckling mice died, and the brains of the adult mice showed no pathology.

Animals↗
PubMed1986

Immunoelectron-microscopical labelling of glycolipids in the envelope of a demyelinating brain-derived RNA virus (Semliki Forest) by anti-glycolipid sera.

Immunoelectron-microscopical techniques using gold-labelled antibodies were used to localize the glycolipids ganglioside, glucocerebroside and galactocerebroside, and spike glycoprotein antigens, in the envelope of the RNA virus Semliki Forest which had replicated in mouse brain cell cultures. The demonstration of host cell membrane glycolipid antigens in viruses is discussed in relation to the possibility of an autoimmune reaction to central nervous system cells.

Animals↗
PubMed1986

Immunological relationship between a demyelinating RNA enveloped budding virus (Semliki Forest) and brain glycolipids.

A monoclonal antibody (MAb) raised against central nervous system (CNS) myelin (212) and a MAb (308) raised against brain with Semliki Forest virus (SFV) were both found to react against the same CNS glycolipids. Both these MAbs were also found to react strongly with SFV and against certain brain glycolipid fractions in an immunosorbent assay (ELISA). This demonstrates the presence of common glycolipid antigens in the viral envelope and CNS myelin. MAb 212 had no SFV neutralising capacity and that of MAb 308 was not significant. However, MAb 212 inhibited the neutralisation of the virus by the MAbs (302, 307) specific to SFV proteins. The implications of these findings in relation to the viral induced CNS autoimmunity and persistence of virus in the CNS is discussed.

Antibodies, Monoclonal↗
PubMed1984

Comparison of protein A-gold and ferritin immunoelectron microscopy of Semliki Forest virus in mouse brain using a rapid processing technique.

Processing tissue for transmission electron microscopy by standard laboratory methods can take two to three days. This makes the development of new techniques time consuming and generally restricts the use of the electron microscope in routine diagnostic work. The possibility of viewing tissue with the electron microscope five hours after sampling using rapid processing techniques is presented. The morphology of the tissue appears undamaged with cell and organelle ultrastructures being readily recognized, as is the presence of virus and its replicating stages. When combined with immunoelectron microscopy a rapid labeling protocol is possible. We have used the technique to develop protein A-gold (6 and 16 nm particles) and ferritin immunoelectron microscopic techniques to demonstrate viral antigens in brain cell cultures and brain tissue from mice infected with Semliki Forest virus.

Animals↗
PubMed1983

Reconstitution of Semliki forest virus infected mice, induces immune mediated pathological changes in the CNS.

Reconstitution of Semliki forest virus infected nude mice with spleen cells from their immunocompetent nu/+ litter mates resulted in an abolition of the otherwise persistent brain virus, production of anti-SFV IgG, and development of normally absent brain pathology. The brain pathological changes, including demyelination, seem to be mediated by T cells, and are maximum 14 days after sensitization of the reconstituting spleen cells. Sensitization of the spleen cells 7 days before transfer to the nude mice results in pathological changes advanced by about 8 days, compared to reconstitution with unsensitized cells. The involvement of T cells in the virus-induced pathology is discussed.

Animals↗
PubMed1982

Blood brain barrier disturbance and immunoglobulin G levels in the cerebrospinal fluid of the mouse following peripheral infection with the demyelinating strain of Semliki Forest virus.

Immunoglobulin G and albumin levels have been measured in the cerebrospinal fluid and serum of Swiss A2G mice following single intraperitoneal inoculation of Semliki Forest virus. This strain of virus used causes a meningoencephalitis followed by immunologically-mediated demyelination. By the use of the levels of immunoglobulin G and albumin in cerebrospinal fluid and serum to calculate the cerebrospinal fluid: serum ratios and the cerebrospinal fluid immunoglobulin G index, it has been shown that the blood-brain barrier breakdown is mild and restricted to within the first 7-8 days after virus inoculation when the inflammatory response is maximal. Immunoglobulin G index provides a measure of synthesis of immunoglobulin G within the blood-brain barrier. Synthesis has been shown to occur from day 10 onwards up to at least day 61 following infection. Arboviruses are known to persist in central nervous system tissue and it is suggested that a continuing immune response within the central nervous system occurs and is perpetuated by persisting virus. Because of the mode of replication of Semliki Forest virus it is also possible that some of the immune response is directed against central nervous system components.

Animals↗
PubMed1982

Immunoglobulin synthesis in nude (nu/nu), nu/+ and reconstituted nu/nu mice infected with a demyelinating strain of Semliki Forest virus.

Infections with the avirulent (A7/74) strain of Semliki Forest virus which causes primary demyelination of the central nervous system in mice have been studied further in nude athymic (nu/nu) mice and their immunocompetent (nu/+) litter mates to measure the production of immunoglobulins. This has been done by radial immunodiffusion and enzyme-linked immunosorbent assays. Half the nude mice examined were able to synthesize specific IgG but at levels 1,000-fold lower than their nu/+ littermates. The majority of nude mice reconstituted with spleen cells from nu/+ mice 1 day before infection with virus were able to synthesize specific IgG nearly as well as the nu/+ animals.

Animals↗
PubMed1982

Lysosomal enzyme changes in macrophages from mice given myocrisin and infected with avirulent Semliki Forest virus.

Myocrisin given to mice i.p. causes depression of lysosomal enzyme activity (acid phosphatase, beta-glucuronidase and N-acetyl-beta-D-glucosaminidase) in peritoneal macrophages. If avirulent Semliki Forest virus (SFV) is given i.p. 3 h after the Myocrisin, further depression of lysosomal enzyme activity occurs, a very high titre of virus is produced in these macrophages and the virus becomes lethal, causing 100% mortality. The possible interrelationships between depressed lysosomal activity, high virus titres and the production of a lethal virus infection are discussed.

Acetylglucosaminidase↗
PubMed1980

Induction of hydrocephalus in mice by i.c. inoculation with a streptococcus isolated in mice following passage of multiple sclerosis brain material.

Following the intracerebral passage in 1-day-old mice of brain material from multiple sclerosis (MS) patients hydrocephalus was produced. An organism, identified as a Streptococcus, was isolated from the hydrocephalic brains. When grown in pure culture the Streptococcus was capable of producing gross hydrocephalus in 1-day-old mice by destruction of the ependyma and blockage of the aqueduct. The organism cannot be allotted to any known streptococcal species nor can it be said at this stage that it is related to MS. The failure to detect bacteria in the original MS brains by bacteriological culture methods makes its origin open to question.

Adult↗
PubMed1980

The effect of mouse strain on the pathogenesis of the encephalitis and demyelination induced by avirulent Semliki Forest virus infections.

Mice from the following strains--Simpson, SWR/J, TO, CBA/Ca, CW (outbred), LAC/G (outbred), SJL/J and Swiss A2G (outbred)--were infected i.p. with avirulent Semliki Forest virus. Clinical signs of disease were noted, histopathological changes assessed and the blood and brain virus infectivities and serum immunoglobulin levels were measured. Only the CW, TO and Swiss/A2G animals showed convincing evidence of demyelination at the light microscopy level but all strains developed encephalitis and microcystic (spongiform) lesions.

Animals↗
PubMed1980

Further studies of macrophages in relationship to avirulent Semliki Forest virus infections.

The amount of virus in macrophages from normal mice infected in vivo and in vitro with avirulent Semliki Forest Virus A7(74)C1 and virulent L10/C1 has been compared to that in macrophages infected similarly from mice given Myocrisin (colloidal gold) before inoculation. Very high titres of virus were found in all macrophages which had been "blockaded" with Myocrisin up to 10(8.5)/ICLD50/ml with the avirulent strain and up to 10(7.2)/ICLD50/ml with the virulent strain. "Blockade" of the macrophages in this way made the normally avirulent strain virulent. The possible reasons for this are discussed.

Animals↗
PubMed1978

Treatment of malignant ascitic and pleural effusion with Corynebacterium parvum.

Six patients with malignant effusions, five from adenocarcinomas and one from a melanoma, were treated by intrapleural or intraperitoneal Corynebacterium parvum. In each case there was a definite reduction in the effusions with a significant decrease in the number of malignant cells; in most cases the effusions stopped completely. Although none of the patients lived for more than a year after treatment, they were undoubtedly more comfortable, as they no longer required frequent paracentesis. In some cases the patients lived for longer than originally expected in a state in which the quality of life was acceptable.

Adenocarcinoma↗