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Biomedical subjects

J Hay

Publications and source records attributed to J Hay.

At least 199 records · Page 11Linked to original sources

Transcription mapping of the varicella-zoster virus genome.

RNA was isolated from varicella-zoster virus-infected Flow 5000 cells (diploid fibroblasts) at late times after infection. With the use of overlapping DNA probes representing all regions of the varicella-zoster genome, an extensive Northern blot analysis of the RNA was carried out. The analysis revealed at least 58 discrete transcripts ranging in size from approximately 0.8 to 6.5 kilobases. RNAs were found to be homologous to all probes used except for those mapping at approximately map unit 0.3, where no RNA transcripts could be detected. Comparison of the sizes and locations of RNA transcripts mapping in the right-hand ends of the varicella-zoster virus and the herpes simplex virus DNAs shows a number of striking analogies, suggesting their similar genomic organization.

Chromosome Mapping↗

Detection of varicella-zoster virus by dot-blot hybridization using a molecularly cloned viral DNA probe.

Varicella-zoster virus (VZV) infection can be definitively diagnosed by isolation of virus in cell culture, a process that usually takes 7-14 days. In order to facilitate the more rapid detection of this virus, we developed a technique for hybridization of DNA from clinical specimens using an in vitro-labeled mixture of cloned fragments of VZV DNA as a probe. The assay can be completed in 36-48 hr and can be successfully carried out in the range of 10 pg to 10 ng of viral DNA. In analyses of 38 specimens from patients with a clinical diagnosis of VZV infection, the results of viral isolation and this assay were highly concordant. The sensitivity of standard cell culture for detection of VZV was 58%, whereas the sensitivity of the assay was 76%, not significantly different (P = 0.14). The specificity of cell culture was 100%, whereas that of the assay was 94% (P = 0.49). The technique appears to be sensitive, specific, and useful for analyses of tissues and body fluids.

Autoradiography↗

Encephalitis in mice with congenital ocular toxoplasmosis.

The brains of mice with congenital ocular toxoplasmosis were examined histologically. Toxoplasma tissue cysts and a subacute/chronic meningo-encephalitis were present in the brains of all infected mice. The findings were very similar to those seen in human congenital toxoplasmosis. The murine model of congenital toxoplasmic encephalitis described in this paper will be valuable in the study of the pathogenesis, natural history and treatment of this condition.

Animals↗

Toxoplasma infection and response to novelty in mice.

Three groups of mice were infected with Toxoplasma and used for behavioral testing using a Y-maze. One group was infected when adult and two groups congenitally, one of these born to dams infected during gestation, the other to dams chronically infected prior to mating. In an initial habituation period each mouse was exposed to a black arm and stem of the maze, entrance to a white arm being blocked by a transparent door. In a subsequent free-choice trial both arms were black and the mouse was free to explore all parts of the maze. During both periods infected mice were more active than controls. Infected mice engaged in less grooming behavior indicative of less approach-avoidance conflict than controls prior to entry into a choice arm at the beginning of the free-choice trial. Infected mice spent more time in the familiar than in the novel (previously blocked) arm during the free-choice trial; conversely, uninfected mice spent more time in the novel than in the familiar arm. It is suggested that the reported behavioural changes would lead to dissemination of the infection in the environment by ultimately making infected mouse intermediate hosts more susceptible to predation by domestic cats, the definitive hosts of Toxoplasma.

Animals↗

Fc-specific reticulo-endothelial clearance in systemic lupus erythematosus and glomerulonephritis.

Fc-specific reticulo-endothelial (R-E) clearance was determined in control subjects (n = 11) and in patients with immune complex (IC) glomerulonephritis (n = 22) and systemic lupus erythematosus (SLE) nephritis (n = 10). Clearance (t1/2) depended on the removal of autologous erythrocytes labeled with 51chromium and sensitized with anti-D IgG by fixed splenic macrophages bearing receptors for the Fc portion of the IgG molecule. A significant difference in clearance rates was demonstrated between normal individuals with and without the HLA-B8, DR3 haplotype. Marked clearance defects were found in SLE (8/10), and t1/2 correlated with the levels of circulating IC. Delayed clearance was also observed in 6/11 patients with IgA nephropathy or Henoch-Schönlein purpura and in 4/11 patients with membranous nephropathy (MN). No correlation was found between circulating IC levels and t1/2 in these diseases. Clearance defects in these patients did not correlate with the presence of the HLA-B8, DR3 haplotype. This study demonstrates that some patients with IC glomerulonephritis have defective Fc-mediated clearance that does not appear to be secondary to IC blockade.

Adult↗

Congenital toxoplasmic retinochoroiditis in a mouse model.

A study of the eyes of adult mice infected in utero with Toxoplasma gondii is reported. The histopathological features of the ocular inflammatory response in the infected mice ranged from minimal damage to complete destruction of the retinal tissue. Notable features such as retinal vasculitis and an almost uniform and highly selective destruction of the photoreceptor layer of the retina suggest a similarity between experimental autoimmune retinitis and the disease process in the retinas of our Toxoplasma-infected mice. We suggest that our mouse model could provide a simple and inexpensive tool for the investigation of immuno-pathological processes in the retina resulting from congenital Toxoplasma infection. The model has the advantage of low post-natal mortality coupled with high ocular morbidity. Furthermore, its aetiology is probably analogous to that of human ocular toxoplasmosis, in that the foetus becomes infected in utero via a mother whose primary infection is acquired during gestation.

Animals↗

Experimental toxocariasis in mice and its effect on their behaviour.

When compared to uninfected controls, mice infected with second-stage larvae of Toxocara canis exhibited: (1) impaired motor performance, (2) increased ambulatory activity, (3) a greater relative preference for more exposed areas and (4) a greater overall preference for novel environments. The infected mice also appeared to show less approach-avoidance conflict and seemed less cautious when presented with novel stimuli. These behavioural differences were independent of measures of general health. Possible explanations for the observed behavioural deficits are discussed. Such alterations in behaviour may be implicated in the continuation of the life-cycle of this parasite by making mouse paratenic hosts more liable to capture and subsequent ingestion by canids, the definitive hosts of T. canis.

Animals↗

The effect of congenital Toxoplasma infection on mouse activity and relative preference for exposed areas over a series of trials.

Previous studies showed that mice with congenital Toxoplasma infections tend to be much more active and tend to show a smaller relative preference for more exposed and novel areas than do uninfected controls. However, in those studies, mice were exposed to behavioural testing procedures once only. Results described here show that these differences (and differences defaecation) are more than just transitory phenomena observed on a first exposure to a novel area. The differences between infected and uninfected mice were clear during each of five separate trials; moreover, they tended to increase from the first to the fifth trial. The possible implications of these findings for the continuation of the life-cycle of the parasite in the environment are considered.

Analysis of Variance↗

Physical mapping of the herpes simplex virus type 2 nuc- lesion affecting alkaline exonuclease activity by using herpes simplex virus type 1 deletion clones.

The nuc- lesion affecting alkaline exonuclease activity in the herpes simplex virus type 2 (HSV-2) mutant ts1348 had previously been mapped to the EcoRI-D restriction enzyme fragment of HSV-1. Eight clones with deletions representing most of HSV-1 EcoRI fragment D were selected with lambda gtWES hybrids. These clones were tested for their ability to rescue the alkaline exonuclease activity of HSV-2 nuc- ts1348 virus. The sequences colinear with the HSV-2 nuc- lesion were found to map between 0.169 and 0.174 map units on the HSV-1 Patton genome, representing an 0.8-kilobase-pair region that is 12.9 to 13.7 kilobase pairs from the left end of HSV-1 EcoRI fragment D.

Animals↗

Tunicamycin enhances the antiviral and anticellular activity of interferon.

The inhibitory effects of interferon on virus multiplication and cell growth are significantly enhanced by treatment with tunicamycin. Potentiation of antiviral activity was found only with enveloped viruses and not with nonbudding viruses. Changes in the plasma membrane of treated cells may account for this effect, since enveloped viruses bud from the cell surface as a terminal step.

Animals↗

The effect of congenital and adult-acquired Toxoplasma infections on the motor performance of mice.

Motor performance was assessed in three groups of mice infected with Toxoplasma. One group was infected when adult. Two groups were infected congenitally: the first was born to dams infected during gestation and the second to dams which were chronically infected prior to mating. All mice were placed individually on a rotating cylinder and the number of falls from it noted over a two-minute period. Infected mice fell significantly more often than uninfected controls. The difference was independent of emotionality (as measured by defaecation) and general body health (as measured by body weight and a subjectively assessed health rating). There was no significant difference in motor performance between the two congenitally infected groups. However, the offspring of mice infected during pregnancy fell significantly more often than mice infected when adult. There were no significant correlations between motor performance and the actual number of Toxoplasma tissue cysts in the brains (or in separate defined sectors of the brains) of infected mice. We suggest that differences between infected and uninfected mice result from pathological changes caused by proliferating toxoplasms in the brains of infected mice. An immunopathological reaction due to the presence of the tissue cysts may also be involved. Other possible factors contributing to observed deficits in motor performance of infected mice are discussed. We suggest that such interference with the motor performance of Toxoplasma infected mice may render them more susceptible to predation by the domestic cat, the definitive host of Toxoplasma.

Animals↗