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Biomedical subjects

D A Tyrrell

Publications and source records attributed to D A Tyrrell.

At least 19 recordsLinked to original sources
PubMed1992

The specificity of antibodies induced by infection with rhinovirus type 2.

Mouse monoclonal antibodies (MAbs) against three distinct antigenic sites on rhinovirus type 2 have been obtained and the sites identified. We describe how these MAbs were used in a blocking test to detect antibodies in human sera directed against the same three defined sites. Sera from twelve volunteers were studied. All had been exposed to rhinovirus type 2 by intranasal inoculation, four had been uninfected, eight were infected of whom four developed a cold while four did not. Blocking antibodies were high and did not increase in the resistant volunteers, and were lower and increased in the infected volunteers. The antibodies were almost as sensitive as other antibody assays for detecting infection. The responses to all three sites were similar. Correlations between the results of all tests were calculated and the results are summarised. Tests were also devised to measure the Ig subclass of antibodies against the whole virus particle. The A1, G1, and G4 classes showed most frequent rises in response to infection. Correlations between these results and other antibody assays were found and are presented.

Antibodies, Monoclonal↗
PubMed1992

A view from the Common Cold Unit.

I have been asked to stand back and describe in broad terms the view I have had of common colds--probably the most frequent of acute human diseases and a long-lasting scientific problem--and in particular our recent work on antivirals. I should be able to do this for two reasons. Like everyone else I have suffered from colds, but in addition I have been studying the problem from the virological and clinical point of view for over 35 years--for the last 31 at the Common Cold Unit, Salisbury. As a result I may have problems with perspective--it is not possible to give a personal view and at the same time to describe something from every possible angle, and quite impossible to be comprehensive, but I have done my best and readers will make their own judgements and corrections.

Antiviral Agents↗
PubMed1992

The common cold, pattern sensitivity and contrast sensitivity.

Results from two studies involving challenge with respiratory syncytial viruses showed that volunteers who developed colds were more sensitive to a visually distracting pattern presented prior to virus challenge than were volunteers who did not get a cold. Volunteers with sub-clinical infections reported more illusions after virus challenge than they had done before, whereas uninfected volunteers and those with colds tended to report fewer illusions on the second test. These effects did not occur when volunteers were challenged with either a coronavirus or rhinovirus. Overall, the results confirm that behavioural measures may be related to susceptibility to subsequent illness, and that viral infections may influence visual perception. They also show that the effects vary according to the nature of the infecting agent, which agrees with results from studies looking at other aspects of behaviour.

Adolescent↗
PubMed1992

An overview of bovine spongiform encephalopathy (BSE) in Britain.

Since 1985 cases of BSE have occurred in increasing numbers in the UK, particularly in dairy herds. Scientist, clinicians and administrators co-operated in showing that this was due to exposure to ruminant-derived meat-and-bonemeal products. The measures used to contain the epidemic and protect biological medicinal products are described. The epidemic will require continued control measures and monitoring until it finally declines.

Animals↗
PubMed1992

Bronchial reactivity to histamine and bradykinin is unchanged after rhinovirus infection in normal subjects.

We investigated the effects of rhinovirus (RV) infection on airways reactivity. Twenty seven normal volunteers (11 atopic) were inoculated with RV 2 or RV EL. The provocative concentrations of histamine and bradykinin required to produce a 15% fall in the forced expiratory volume in one second (FEV1) (PC15FEV1) were measured before, 7 and 21 days after inoculation. Infection was determined by a fourfold rise in anti-viral antibody titre and by viral culture from nasal washings. Peak expiratory flow rate (PEF) was recorded three days before and for 21 days after inoculation. All subjects underwent the first two bronchial challenges, and 22 the third challenge. For the whole group and for atopic subjects, there were significant correlations between the PC15 values for bradykinin and histamine (r = 0.82 and r = 0.85, respectively). Twenty subjects were infected; six had clinical colds. For the 16 infected subjects who had all three challenges, the median (range) PC15FEV1 for the histamine challenges was 36 (0.89-64), 62 (1.5-64) and 34 (0.94-64) mg.ml-1, respectively, and 32 mg.ml-1 for each bradykinin challenge (range: 0.015-32, 0.088-32 and 0.033-32). There were no significant differences between study days for PC15FEV1 histamine or bradykinin for the whole group, the infected subjects, those with clinical colds or for those infected with either RV subtype. There was no significant change in mean daily PEF after viral infection. We conclude that airways reactivity to histamine and bradykinin is unchanged after experimental RV infection in normal volunteers.

Administration, Inhalation↗
PubMed1991

Psychological stress and susceptibility to the common cold.

BACKGROUND: It is not known whether psychological stress suppresses host resistance to infection. To investigate this issue, we prospectively studied the relation between psychological stress and the frequency of documented clinical colds among subjects intentionally exposed to respiratory viruses. METHODS: After completing questionnaires assessing degrees of psychological stress, 394 healthy subjects were given nasal drops containing one of five respiratory viruses (rhinovirus type 2, 9, or 14, respiratory syncytial virus, or coronavirus type 229E), and an additional 26 were given saline nasal drops. The subjects were then quarantined and monitored for the development of evidence of infection and symptoms. Clinical colds were defined as clinical symptoms in the presence of an infection verified by the isolation of virus or by an increase in the virus-specific antibody titer. RESULTS: The rates of both respiratory infection (P less than 0.005) and clinical colds (P less than 0.02) increased in a dose-response manner with increases in the degree of psychological stress. Infection rates ranged from approximately 74 percent to approximately 90 percent, according to levels of psychological stress, and the incidence of clinical colds ranged from approximately 27 percent to 47 percent. These effects were not altered when we controlled for age, sex, education, allergic status, weight, the season, the number of subjects housed together, the infectious status of subjects sharing the same housing, and virus-specific antibody status at base line (before challenge). Moreover, the associations observed were similar for all five challenge viruses. Several potential stress-illness mediators, including smoking, alcohol consumption, exercise, diet, quality of sleep, white-cell counts, and total immunoglobulin levels, did not explain the association between stress and illness. Similarly, controls for personality variables (self-esteem, personal control, and introversion-extraversion) failed to alter our findings. CONCLUSIONS: Psychological stress was associated in a dose-response manner with an increased risk of acute infectious respiratory illness, and this risk was attributable to increased rates of infection rather than to an increased frequency of symptoms after infection.

Adolescent↗
PubMed1991

Prophylactic intranasal alpha 2 interferon and viral exacerbations of chronic respiratory disease.

BACKGROUND As respiratory virus infections often lead to exacerbations of chronic bronchitis and asthma an effective antiviral drug may be helpful in such patients. Alpha 2 interferon has been shown to give protection against rhinovirus infections in field studies. METHODS Patients with chronic respiratory disease exposed to close contacts with symptoms of upper respiratory tract infection were randomly allocated to receive nasal sprays of recombinant alpha 2 interferon (3 x 10(6) IU) or placebo twice daily for five days. Of the 123 patients recruited into the study, 69 took 117 courses of medication; 11 courses were excluded from analysis. RESULTS No important side effects were recorded and the incidence of possible adverse effects was similar in the two groups. Interferon treatment did not reduce the number or severity of symptomatic episodes; 11 of 48 patients given interferon and 16 of 58 given placebo developed lower respiratory symptoms. There were no differences in mean symptom scores (51 interferon and 52 placebo), number of symptomatic days (3.3 interferon and 5.0 placebo), peak flow values, number of general practitioner consultations, or use of antibiotics. CONCLUSION Alpha 2 interferon 3 x 10(6) IU taken twice daily for five days does not protect patients with chronic respiratory disease from exacerbations after they have been in contact with an upper respiratory tract infection.

Administration, Intranasal↗
PubMed1990

A host-cell-selected variant of influenza B virus with a single nucleotide substitution in HA affecting a potential glycosylation site was attenuated in virulence for volunteers.

An influenza B virus was passaged in man (virus A) and then in human embryo trachea (C) and into embryonated eggs (D) or directly into eggs (B). Virus A, B, and C had the same (cell-like) haemagglutinin phenotype on reaction with selected monoclonal antibodies while D had an "egg-like" phenotype. The viruses were administered at a dose of 1,000 TCD50 (for MDCK cells) by intranasal inoculation to groups of 27 or 28 volunteers. Viruses A, B, and C all produced disease in six to eight volunteers, whereas D produced no illness and only four volunteers were infected. The viruses shed by the volunteers were indistinguishable from those with which they were inoculated. The haemagglutinin genes of the viruses were sequenced and changes were detected indicating amino acid substitutions at position 196-198 in the attenuated egg-grown virus D whereby a potential glycosylation site present in the other viruses was lost.

Amino Acid Sequence↗
PubMed1990

The efficacy of intranasal interferon alpha-2a in respiratory syncytial virus infection in volunteers.

In a double-blind, placebo-controlled study, self-administered intranasal interferon alpha-2a or placebo was given both before and after challenge with respiratory syncytial virus. The incidence of colds and the severity of signs and symptoms were reduced in those receiving interferon alpha-2a as compared with those given placebo. In a further double-blind, placebo-controlled study, self-administered interferon alpha-2a or placebo was given only to those volunteers who developed colds following challenge with respiratory syncytial virus. There was no evidence that interferon alpha-2a reduced the severity of the signs and symptoms or shortened the duration of the illness. The similarity of these results to the effect of interferon alpha-2a in rhinovirus infections in volunteers is discussed.

Administration, Intranasal↗
PubMed1990

Determinants of susceptibility to challenge and the antibody response of adult volunteers given experimental respiratory syncytial virus vaccines.

The virulence and immunogenicity of a wild-type respiratory syncytial (RS) virus together with four temperature sensitive (ts) mutants derived from this isolate were tested by intranasal inoculation into adult volunteers. Resistance to challenge correlated with neutralizing antibody titres in nasal secretions and to a lesser extent in serum. All ts mutants were reduced in virulence. Mutant ts1B caused mild or asymptomatic infections yet induced antibody responses comparable with wild-type RS virus. Ts1B might be developed further to produce a live-virus vaccine.

Adult↗
PubMed1990

The time course of the immune response to experimental coronavirus infection of man.

After preliminary trials, the detailed changes in the concentration of specific circulating and local antibodies were followed in 15 volunteers inoculated with coronavirus 229E. Ten of them, who had significantly lower concentrations of pre-existing antibody than the rest, became infected and eight of these developed colds. A limited investigation of circulating lymphocyte populations showed some lymphocytopenia in infected volunteers. In this group, antibody concentrations started to increase 1 week after inoculation and reached a maximum about 1 week later. Thereafter antibody titres slowly declined. Although concentrations were still slightly raised 1 year later, this did not always prevent reinfection when volunteers were then challenged with the homologous virus. However, the period of virus shedding was shorter than before and none developed a cold. All of the uninfected group were infected on re-challenge although they also appeared to show some resistance to disease and in the extent of infection. These results are discussed with reference to natural infections with coronavirus and with other infections, such as rhinovirus infections.

Antibodies, Viral↗
PubMed1990

The radiation dosimetry of 99Tcm-exametazime.

The biodistribution of the regional cerebral perfusion imaging agent, 99Tcm-exametazime, has been studied with volunteer subjects at Aberdeen, Homburg, Manchester and Milan. Data from these studies have been pooled and analysed to formulate a kinetic biodistribution model, allowing estimation of time integrals of activity in various body organs. Estimates of radiation dose to humans injected with this material have been made by applying the MIRD formalism to these data. The highest doses occur to the lachrymal glands, gallbladder and kidneys (33, 27 and 18 mSv, respectively, per 500 MBq administered.) The lachrymal glands were visualized in only 6 of the 26 volunteer studies. The effective dose equivalent, for the worst case individual, is 8.3 mSv. In the majority of subjects where there was no uptake in the lachrymal gland, the effective dose equivalent reduces to 6.9 mSv.

Adult↗
PubMed1990

The effect of intranasal nedocromil sodium on viral upper respiratory tract infections in human volunteers.

Two studies involving double-blind group comparative trials in human volunteers compared the effects of intranasal nedocromil sodium (2.6 mg active drug per nostril, q.i.d.) with placebo on clinical symptoms and performance impairment associated with the common cold. In the first study volunteers were challenged with rhinoviruses (RV9 and RV14), and in the second study with respiratory coronavirus. In both studies, active and placebo groups of volunteers were demographically similar. Infection rates in both groups were also similar. There were no withdrawals resulting from unusual symptoms related to either treatment. In the rhinovirus study (19, placebo; 20, nedocromil sodium) daily symptom scores and daily mean nasal secretion weights were significantly lower in the nedocromil sodium-treated group. In the coronavirus study (26, placebo; 27, nedocromil sodium) there was little difference in the severity of colds between the active and placebo-treated groups, but trends favoured nedocromil sodium. In both studies the impairment of performance in volunteers who developed a cold was significantly less in those treated with nedocromil sodium than in those treated with placebo.

Administration, Intranasal↗
PubMed1990

Pathogenicity for humans of human rhinovirus type 2 mutants resistant to or dependent on chalcone Ro 09-0410.

Mutants of human rhinovirus type 2 (HRV-2) resistant to and dependent on the antirhinoviral compound chalcone Ro 09-0410 were selected in cell culture under clean laboratory conditions. A total of 42 volunteers were challenged with either the drug-resistant mutant [SR2-410(r)] (15 volunteers), the drug-dependent mutant [SR2-410(d)] (15 volunteers), or a wild-type HRV-2 which had a similar passage level in vitro as the mutants but without the drug (12 volunteers). Of volunteers challenged with the wild-type HRV-2, 33, 67, and 82% developed cold symptoms, shed virus, and showed serological evidence of infection, respectively. In contrast, only 13, 27, and 23% of volunteers challenged with the drug-resistant mutant developed colds, shed virus, and showed serological evidence of infection, respectively. None of the volunteers challenged with the drug-dependent virus became infected or had symptoms of colds. These results demonstrate that a drug-resistant rhinovirus was capable of infecting humans and producing disease, although its infectivity was reduced when compared with that of the wild type. In contrast, a drug-dependent virus had lost its ability to infect humans.

Adolescent↗
PubMed1990

Effects of experimentally induced colds on aspects of memory.

Four experiments were carried out to investigate the effects of experimentally-induced colds on various aspects of memory of 27, 47, 39, and 30 adults. Free recall, digit span, and retrieval from semantic memory were unaffected by having a cold. Immediate recognition of important information from a story was impaired in subjects with colds, which suggests they were less able to follow the theme of the story. In contrast to this, volunteers with colds had better recognition of information from a story learned prior to the virus challenge.

Adult↗