Biomedical subjects

J Gairns

Publications and source records attributed to J Gairns.

5 recordsLinked to original sources

PubMed2000

Replication of the herpes simplex virus type 1 RL1 mutant 1716 in primary neuronal cell cultures--possible relevance to use as a viral vector.

The herpes simplex virus type 1 (HSV-1) RL1 deletion mutant 1716 has properties that make it a promising candidate as a viral vector for gene therapy in the human nervous system. These properties include its ability to spread along neural pathways and establish a latent infection in post-mitotic neurons, while retaining a non-virulent phenotype in vivo and an inability to cause a lytic infection in stationary or fully differentiated cells. In this study, we used viral replication assays and indirect immunofluorescence to investigate the ability of 1716 to bind to, enter, express genes and produce progeny virus in dissociated neuronal cell cultures prepared from rat hippocampal, medial septal and dorsal root ganglion (DRG) tissues and in primary rat astrocyte cultures. Both heterogeneous cultures and those that had been enriched for neurons were employed. Following both low and high multiplicities of virus infection, the behaviour of 1716 was compared with its wild-type parent HSV-1 strain 17 in these cultures. It was found that the growth of 1716 was significantly impaired compared to wild type HSV-1, with these differences being magnified at lower multiplicities of viral infection as well as in neuron-enriched cultures: this impairment is likely to be due to decreased replication, as immunofluorescence assays showed that 1716 bound to, entered and expressed genes in all neuronal cell types and astrocytes with similar efficiency to the wild type virus. This ability of 1716 to enter and express genes in different neuronal populations demonstrates its potential suitability as a viral vector.

Animals↗

PubMed1995

Attempted modulation of herpes simplex virus (HSV) infection of neurons in culture by fibroblast growth factor.

It has been suggested that fibroblast growth factor (FGF) receptors may mediate entry of herpes simplex virus (HSV) to susceptible cells. We investigated the possible modulation of acute lytic HSV infection of cultured rat neurons by basic FGF, using cell-specific markers and indirect immunostaining. Dissociated neural cell cultures were prepared from the medial septal region of the basal forebrain, the hippocampus and dorsal root ganglion (DRG). The proportion of neurons in the cultures was enhanced by the addition of cytosine arabinoside (2 microM) in the hippocampal and DRG cultures and by inversion of the coverslips in septal cultures. The percentage of MAP2+ and neurofilament+ neurons in these cultures varied between 9 and 95%. Cultures were treated with basic FGF (4-5 ng ml-1) continuously and infected with wild-type HSV-1, untreated uninfected cultures acting as controls. Both FGF binding and FGF receptors were demonstrated in hippocampal, and to a much lesser extent, DRG neurons. In repeated experiments it was found that FGF treatment did not have a significant effect on lytic infection in any of the neuronal populations studied as assessed by the development of viral antigen expression and comparison of identified neurons in FGF, treated versus untreated, infected cultures. Our data show that FGF does not have a 'neuroprotective' effect on HSV infection of either central or peripheral neurons.

Animals↗

PubMed1992

Major histocompatibility complex (MHC) antigen expression in HIV encephalitis.

In order to study possible immunopathogenic mechanisms in Human Immunodeficiency Virus (HIV) encephalitis, immunocytochemical localization of Class I and Class II major histocompatibility complex (MHC) antigens was studied in formalin-fixed tissue sections from the brains of 10 individuals who had died with this disorder. Using the avidin biotin peroxidase technique and monoclonal antibodies to these antigens, increased expression of Class I antigens was found in five out of 10 and of Class II antigens in six out of 10 cases of HIV encephalitis. This contrasted with results obtained with the HIV-specific anti-P24 antibody which reacted with only a small number of cells in four cases. Class I and II antigens were detected mainly in perivascular monocytes/macrophages and also in multinucleated giant cells. In two cases, slight labelling was also detected in these cells more diffusely in the brain parenchyma. Immune and viral antigens were not detected in glial cells or neurons. Neither normal control cases nor brain sections from patients who had died from other neurological diseases were labelled with any of the antibodies apart from two cases of varicella-zoster virus-associated encephalitis in which increased expression of Class II antigens occurred. These findings support the notion that indirect immune-mediated mechanisms may be important in the pathogenesis of HIV encephalitis.

Encephalitis↗

PubMed1989

Family studies of congenital heart block associated with Ro antibody.

Complete congenital heart block is associated with the presence of maternal autoantibodies to small ribosomal nucleoproteins (such as anti-Ro) which cross the placenta and may be deposited at the site of cardiac damage. Ten such cases of congenital heart block, their mothers, and their siblings were studied. The seropositive mother of one case had a similar conduction defect (bifascicular block) to that in her affected child. None of the siblings examined had cardiac lesions. Six mothers had Ro or La antibody five to 17 years after the birth of the affected child. Four mothers examined 11-32 years after the birth of an affected child were seronegative. Three of these mothers had evidence of a connective tissue disorder. This evidence is consistent with a hypothesis that a maternal viral infection, associated with autoantibody production, leads to virus crossing the placenta, damaging the fetal heart, and eliciting local deposition of maternal antibody.

Adolescent↗

PubMed1987

Cardiac damage in polymyositis associated with antibodies to tissue ribonucleoproteins.

Cardiac damage, consisting of mild diffuse myocarditis or severe inflammation and fibrosis of the conduction system or both, occurs in more than 70% of patients with idiopathic polymyositis. The lesions are strikingly similar to those detected in the infants of mothers with connective tissue diseases. In these infants the damage is associated with the transplacental passage of a maternal antibody to tissue ribonucleoproteins (anti-Ro). The same antibody was identified in 60% of 55 patients with polymyositis and in 69% (23/33) of those with associated cardiac damage including four with complete heart block. Forty five per cent of those patients who were anti-Ro seropositive had no clinical or electrocardiographic evidence of cardiac lesions. They were in the acute phase of illness, however, and no other more detailed heart investigations had been done. It is postulated that cardiac damage in polymyositis is caused by the antibody and that its presence may serve as a marker for heart involvement.

Adolescent↗