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Biomedical subjects

D A Tyrrell

Publications and source records attributed to D A Tyrrell.

At least 55 records · Page 3Linked to original sources
PubMed1989

Use of synthetic oligonucleotide probes to detect rhinovirus RNA.

Current methods of detecting a human rhinovirus (HRV) infection are either based on isolation of virus in appropriate susceptible cell lines, which is time-consuming and requires considerable expertise, or are dependent on knowing the serotype. The existence of over 100 immunologically distinct serotypes makes serotype specific assays, such as ELISA, unsuitable for general diagnostic assays. In this study a general rhinovirus assay is described which utilises synthetic oligonucleotides as probes in a filter hybridization assay. The probes are designed to bind to short but highly conserved regions of the rhinovirus genome. Indeed, the probes successfully detected all 57 rhinovirus serotypes tested. Furthermore, the test was used to demonstrate rhinovirus infection in clinical samples from 57 volunteers, inoculated with HRV, collected on six consecutive days. Clinical samples were taken prior to inoculation and on days 2-7 after inoculation. The filter hybridization assay gave results comparable to virus culture on days 2 and 3 post-inoculation, but was more sensitive on subsequent days.

Base Sequence↗
PubMed1989

Rhinovirus detection using probes from the 5' and 3' end of the genome.

This study investigated the abilities of cDNA probes from the 5' and 3' ends of the genome of human rhinoviruses (HRV-) 14, 9, and 1B to detect RNA from 59 rhinovirus serotypes. The results show that probes from the 5' end of the genomes of HRV-14, 9, and 1 B detected a large number of serotypes but the detection rate was variable and depended on the degree of homology with the particular probe. In contrast, all the 3' end probes were specific for the homologous virus. However, a long HRV-9 probe detected a large number of serotypes. It was concluded that such cDNA probes would not detect all serotypes with equal efficiency. Synthetic oligonucleotides corresponding to short but highly conserved regions in the 5' non coding region may overcome this problem.

DNA Probes↗
PubMed1989

A re-investigation of the behavioural effects of intracerebral injection in marmosets of cytopathic cerebrospinal fluid from patients with schizophrenia or neurological disease.

In experiments designed to investigate transmission, cerebrospinal fluid (CSF) from patients with schizophrenia or neurological disease (Huntington's disease) which had been found to induce a cytopathic effect (CPE) in human embryonic fibroblast cell culture was injected intracerebrally into common marmosets. Behavioural observations were made on the animals during a period of 2 1/2 years prior to injection and for 2 1/2 years after injection. In an earlier study (Baker et al. 1983 b) we found that animals injected with CPE + ve CSF became progressively more inactive when compared with those injected with non-cytopathic (CPE -ve) CSF from control patients. In the present study we were unable to replicate this finding. No difference in behaviour emerged between animals injected with control CSF and animals injected with CSF from schizophrenics or patients with neurological disease, nor between animals injected with CPE + ve CSF and animals injected with CPE -ve CSF. The numbers of offspring produced and surviving did not differ between the groups. We conclude that the original findings were due to factors unconnected with the nature of the injected material.

Animals↗
PubMed1989

The time course of the humoral immune response to rhinovirus infection.

The specific humoral immune response of 17 volunteers to infection with human rhinovirus type 2 (HRV-2) has been measured both by neutralization and by ELISA. Six volunteers who had HRV-2-specific antibodies in either serum or nasal secretions before HRV-2 inoculation were resistant to infection and illness. Of the remaining 11 volunteers who had little pre-existing HRV-2-specific antibody, one was immune but 10 became infected and displayed increases in HRV-2-specific antibodies. These antibodies first increased 1-2 weeks after infection and reached a maximum at 5 weeks. All six resistant volunteers who had high pre-existing antibody and eight of the volunteers who became infected maintained their HRV-2-specific antibody for at least 1 year. At this time they were protected against reinfection. Two volunteers showed decreases in HRV-2-specific antibodies from either serum or nasal secretions. They became infected but not ill after HRV-2 inoculation 1 year later.

Adult↗
PubMed1989

Use of sodium iodide to overcome the eluate age restriction for Ceretec reconstitution.

The Ceretec kit for preparation of 99Tcm-hexamethylpropyleneamine oxime (HMPAO) complex for the investigation of regional cerebral blood flow requires careful handling by the radiopharmacist and a number of restrictions have been placed on the kit relating to the nature of 99Tcm generator eluate used for reconstitution. The addition of sodium iodide to eluate immediately after elution can remove one of these restrictions. A level of 0.4 mg sodium iodide added after elution allows reconstitution of Ceretec up to 6 h later with no adverse effect on radiochemical purity. This offers a simple method for the use of this product if availability of fresh technetium generator eluate is a constraint.

Hydrogen-Ion Concentration↗
PubMed1989

99Tcm-labelled meso-HMPAO and glutathione content of human lung tumours.

Levels of reduced glutathione (GSH) are increased in some types of malignant tumours and are known to influence the response to radio- and chemotherapy. In vitro studies suggest a correlation between cellular GSH concentration and retention of the meso form of hexamethyl propyleneamineoxime (HMPAO). This study investigates the relationship between in vivo tissue retention of 99Tcm-labelled HMPAO and GSH concentration in ten patients referred for thoracotomy for possible lung cancer. Retention of 99Tcm-HMPAO was measured using single photon emission computed tomography (SPECT). The tumour and normal lung concentration of reduced glutathione (GSH) was measured in tissue specimens collected peroperatively. Malignancy was confirmed in eight patients. Of seven patients undergoing curative resection for carcinoma, tumour GSH concentration was higher (mean 2.76 mM) than normal lung (mean 1.04 mM). In one neurofibroma, the GSH concentration was 1.80 mM. No correlation was found between 99Tcm meso-HMPAO retention and either the tumour GSH concentration or the tumour:lung GSH ratio. The results from this small series demonstrate that the intracellular GSH concentration of malignant lung tumours is generally higher than that in normal lung but that meso-HMPAO retention could not be used to predict these levels.

Carcinoma, Non-Small-Cell Lung↗
PubMed1989

Suppression of colds in human volunteers challenged with rhinovirus by a new synthetic drug (R61837).

This report describes double-blind placebo-controlled trials of a new synthetic antirhinovirus drug, R61837, which showed it to be effective in suppressing colds in human volunteers challenged with rhinovirus type 9. In one trial, R61837 was given by intranasal spray six times a day, commencing 28 h before virus challenge; treatment continued for 4 days and one dose (total dose, 25 mg). This regimen suppressed symptoms until 48 h after medication ceased, at which time colds developed. In another trial, medication with R61837 commenced at 4 h before virus challenge and continued for a total of 6 days (total dose, 36 mg). The drug produced substantial reductions in both the mean daily clinical score and the mean daily nasal secretion weight compared with patients given the placebo. These differences reached statistical significance for 2 and 4 days, respectively. In a further trial, intranasal R61837 was not effective in treating colds even when given shortly after the onset of symptoms and in doses of up to 15 mg/day.

Administration, Intranasal↗
PubMed1989

Effects and after-effects of the common cold and influenza on human performance.

Volunteers who develop a cold following virus challenge were significantly slower on choice reaction time tasks than those with no illness. This effect was still observed after the clinical symptoms had gone. In contrast to this, influenza illnesses only impaired performance in tasks in which subjects were uncertain where the target stimulus would appear. These results demonstrate that the CNS effects of respiratory virus infections depend on the type of virus, and that performance impairments may remain even after the symptoms of a cold have gone.

Adult↗
PubMed1988

Failure to demonstrate synergy between interferon-alpha and a synthetic antiviral, enviroxime, in rhinovirus infections in volunteers.

Marked synergy between the antirhinoviral effect of rHuIFN alpha and enviroxime has been observed in vitro but an attempt to demonstrate it in volunteers was unsuccessful. The sub-optimal intranasal dose of rHuIFN alpha (0.18 Mu four times daily for 4 1/4 days) used prophylactically in the trial did reduce the severity of colds induced by RV9 and 14, but the difference did not reach statistical significance and was not enhanced by the administration of enviroxime (0.28 mg six times daily for six days). The main reason for failure is thought to be the rapid removal of enviroxime from the nose when given intranasally.

Adolescent↗
PubMed1988

Towards anti-HIV vaccines.

There is a great deal of experience on the development and testing of antiviral vaccines but, in the case of HIV, it will be necessary to analyse carefully our understanding of the biology of the organism, the natural history and pathology of the disease (in particular immunity or resistance to infection or clinical symptoms), the possible sources of antigens and methods of formulating and administering them. Only then, and after successful initial trials, will it be possible to propose rational programmes for their use. This article indicates how discussions will be structured and the directions in which they might go, but needs to be supplemented by much more factual information and refined with further opinions and judgements on probable outcomes.

Acquired Immunodeficiency Syndrome↗
PubMed1988

The effects of experimentally induced respiratory virus infections on performance.

Studies of experimentally induced respiratory infections and illnesses showed that influenza impaired performance on a visual search task but had no effect on a simple motor task, whereas colds impaired the motor task but not the search task. The effect of influenza on the search task was observed in both volunteers with significant clinical symptoms and volunteers who were shown, by virological techniques, to be infected but who had no significant clinical illness. Performance was also impaired during the incubation period of this illness, which confirms that subclinical influenza virus infections can have behavioural effects. In contrast to influenza, the effects of colds were restricted to volunteers who had significant clinical symptoms, and the impairments in performance were observed only when the symptoms were apparent.

Adolescent↗
PubMed1988

Recombinant human interferon-gamma as prophylaxis against rhinovirus colds in volunteers.

The first evaluation of intranasal (i.n.) recombinant human interferon-gamma (rHuIFN-gamma) as prophylaxis against experimental rhinovirus (RV) infection and illness in volunteers is reported. In two studies, 7 of 27 (26%) of the volunteers who received rHuIFN-gamma (2 Mu i.n. 3 x /day) had either blood stained nasal secretions or nose bleeding which was not observed in any of the 26 placebo recipients. Some volunteers given rHuIFN-gamma showed increased nasal secretion and the majority complained of slight nasal stuffiness, whereas only a few of those receiving placebo complained of these symptoms. In the prophylactic study, 17 volunteers were given the above regimen of rHuIFN-gamma and 17 placebo; after the fourth dose all were challenged with RV9, followed 1 h later with RV14 (100 TCID50 of each virus). Compared with the placebo-treated controls, interferon recipients showed no significant reduction in the proportion who developed colds or became infected, and there was an increase in both their mean clinical scores and mean nasal secretion weights. Thus i.n. rHuIFN-gamma did not prevent rhinovirus infection or illness and may enhance the symptoms.

Administration, Intranasal↗
PubMed1988

Influence of atopy on the clinical manifestations of coronavirus infection in adult volunteers.

In an attempt to understand the relationship between viral upper respiratory tract infection and the underlying virological and immunological mechanisms, thirty-four volunteers were inoculated intranasally with coronavirus 229E; subsequent virus shedding and/or antibody rises, indicating active infection, were observed in twenty-nine. There was a greater increase in independently measured scores of clinical severity, e.g. cold symptoms, in those with detectable IgE in nasal secretions (P less than 0.01). A similar association was found between clinical scores and serum IgE concentrations greater than or equal to 150 IU/ml, but the relationship with systemic atopy, as assessed by skin-prick tests to common allergens, was less marked. A more detailed study of twelve of the infected volunteers failed to explain these findings on the basis of mast cell mediator release, as concentrations of leukotriene B4, the sulphidopeptide leukotriene C4, and histamine, were not appreciably elevated in the nasal secretions following virus inoculation. Similarly, there was no evidence that circulating coronavirus specific IgE was produced. Thus, this study suggest that atopy may be related to the severity of cold symptoms produced by coronavirus 229E, although the exact connection has yet to be determined.

Adolescent↗
PubMed1987

Failure of intranasally administered 4', 6-dichloroflavan to protect against rhinovirus infection in man.

4',6-Dichloroflavan, a potent inhibitor of rhinovirus replication in tissue culture systems was tested in a double-blind, placebo-controlled volunteer trial for its protective efficacy against experimental rhinovirus infection. Dichloroflavan was administered intranasally as a 5 per cent w/v aqueous suspension (40 mg; 5 times per day) for 5 doses before and 21 doses after intranasal challenge with rhinovirus type 9, a virus type known to be highly sensitive to the drug when tested in tissue culture. A total of 49 volunteers were included in the efficacy analysis. Dichloroflavan did not produce any consistent or significant reduction in clinical or laboratory parameters of infection. Indeed there was some indication that treatment with the drug may have been associated with increased severity of clinical signs and symptoms. Dichloroflavan administered intranasally is not, therefore, of value in the prevention of human rhinovirus infection.

Administration, Intranasal↗