Biomedical subjects
Publications and source records attributed to D A Tyrrell.
The working of a 19-bed isolation unit in a general hospital was studied from August 1975 to July 1976. A few patients received the highest degree of isolation, but infections in all categories were contained and patients at risk in the same unit were protected from infection.
A girl aged 12 developed pseudomembranous colitis after a short course of oral penicillin. She had no history of adverse reaction to penicillin before or after the illness. No pathogenic bacteria, mycoplasmas, or viruses were found in her faeces, but they did contain a toxin. Toxin was also found in four of five other patients with pseudomembranous colitis but not in six specimens obtained from patients with diarrhoea caused by other disorders. Further studies may show that pseudomembranous colitis is caused by a bacterial toxin.
We have studied the interactions of liposomes with human skin fibroblasts and mouse P815Y mastocytoma cells in culture, and the perfused rat liver, with the following findings. 1. In all the systems studied serum was found to cause an increase in the uptake of a [14C]cholesterol label into cells from anionic and neutral liposomes and a decrease in the uptake of the label from cationic liposomes. 2. Evidence suggests that albumin enhances the exchange/transfer of [14C]-cholesterol between liposomes and cultured cells. 3. With [14C]cholesterol in the liposome bilayer and [3H]methotrexate entrapped in the aqueous spaces of the liposome, the alpha- and beta-globulin fractions of serum decreased the transfer of both labels from cationic liposomes into cultured cells and the perfused rat liver. The beta-globulin fraction caused increased leakage of methotrexate from fluid liposomes of all charges. 4. The alpha- and beta-globulin fractions of serum appear to enhance the uptake of anionic liposomes into the perfused rat liver.
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Respiratory viruses are not generally carried by normal subjects and cannot persist in small isolated communities. When infection does occur epidemics are seen and the illness may be more severe than in the outside world. These points are illustrated by reference to studies on the island of Tristan da Cunha and stations of the British Antarctic Survey.
Groups of student volunteers were immunized with one of five different inactivated influenza virus vaccines. The concentration of virus in the various vaccines differed by both the international unitage test and by the concentration of haemagglutinin, as measured by the single radial diffusion test; the results of the two methods of standardization showed no correlation. The serum HI response to immunization was variable; volunteers given A/England/72 showed a 16.6-fold increase in homologous serum antibody titre whilst volunteers given A/Hong Kong/68 vaccine showed a 4.2-fold increase. The variable response of volunteers to immunization could not be explained by the varied concentration of virus in the vaccines, as measured by either test, the titres of serum HI antibody present before immunization, or a combination of these two factors.The ability to infect volunteers with WRL 105 virus 4 weeks after immunization with heterologous, inactivated virus vaccine was directly related to the degree of cross-reactivity between the haemagglutinins of this vaccine virus and WRL 105 virus. Thus, the greatest number of infections by the challenge virus were seen in volunteers given A/Hong Kong/68 vaccine, less were observed in volunteers given A/England/72 vaccine, and least were found in groups given A/Port Chalmers/73 or A/Scotland/74 vaccine. However, compared with the incidence of infection in volunteers given B/Hong Kong/73 vaccine, all the heterologous influenza A vaccine gave some immunity to challenge infection.
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A randomised controlled trial was carried out to study the effect of 10 g of ascorbic acid taken during the first 2 1/2 days on the symptoms of the common cold. Altogether 1524 volunteers were recruited from a number of working groups in different parts of the country; 482 developed colds. There was no evidence that upper respiratory or general constitutional symptoms were alleviated by ascorbic acid. Among the men who had any colds at all, significantly fewer on active than on placebo treatment had two or more colds; however, this effect was not seen in women. Ascorbic acid is of no value in the treatment of the common cold; its preventive effect, if any, is not such as to justify advising its general use as a prophylactic measure.
Human leucocyte interferon has been shown to prevent rhinovirus infection if given intranasally to human volunteers. This finding encourages further investigation, but it is too soon to say whether interferon is likely to be clinically useful in serious virus infections of the respiratory tract.
Bacterial infection contributes substantially to the morbidity and mortality of human influenza. In vitro experiments were performed to test two hypotheses regarding a possible relationship between the virus and bacterial infection. Firstly, maintenance media from tissue and organ cultures infected with influenza virus were tested for the presence of staphylococcal growth-promoting factors; no evidence for these was found. Secondly, we looked for a virus effect on polymorphonuclear leucocyte function. We found that human leucocytes purified from venous blood and exposed to influenza virus responded normally to stimulation of hexose monophosphate shunt activity and chemiluminescence. However, their responses in tests of phagocytic function and of chemotaxis were inhibited. By various criteria this effect was specific to the virus and could be obtained even when only a few virus particles were present per leucocyte. We propose that this is a mechanism by which influenza virus could enhance susceptibility to bacterial infection in the lung.
In human and in cow's milk an antiviral activity has been detected which does not seem to be related to antibodies or other known virus inhibitors. The antiviral activity lay in a relatively heat-stable macromolecule belonging to the non-fatty part of milk.
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The clinical and antibody responses of volunteers to three intradermal schedules of human diploid cell strain rabies vaccine (0.4 ml on day 0; 0-1 ml on days 0, 1, 2, 3; and 0-1 ml on days 0, 3, 7, and 14) are described. Vaccine was administered to 114 contacts of two rabid patients in order to evoke a rapid antibody response and the antibody titres of 30 of those who were vaccinated and bled were measured. High antibody titres were obtained in all subjects irrespective of their immunisation schedule; there were only minimal local reactions. All volunteers had titres greater than 1/78 (1.7 I.U./ml) by day 14, and 7 of 10 receiving 0.1 ml into each limb on day 0 had detectable antibody by day 7.
The acceptability, reactivity, and antibody responses of recombinant WRL 105 strain, live, attenuated influenza virus vaccine administered intranasally were studied in seventeen normal adults, and in seventeen bronchitic and twenty-one geriatric volunteers. The effect on peak flow and 1-second forced expiratory volume (F.E.V.1) on the 3rd, 5th, and 7th days after vaccination was measured in the bronchitic and normal groups. Seroconversion occurred in 80% to tht homologous virus, in 40.6% to A/Victoria/3/75, and in 26.5% to A/England/864/75 in subjects with pre-vaccination haemagglutination inhibition titres of less than 1/40. A fourfold or greater increase in homologous anti-neuraminidase antibody was found in 48% of twenty-seven infected subjects when measured by a new elution inhibition technique. The frequency and nature of symptoms were similar in both infected and non-infected groups. No significant changes in F.E.V.1 occurred, but on days 5 and 7 there was a decrease in peak flow measurements in both infected and non-infected groups when assessed as the percentage change of the pre-vaccination value.
The X-31 strain of influenza A (H3N2) virus has been covalently bound to CNBr activated agarose for the separation of anti-haemagglutinin antibodies. The virus immunoadsorbent was used repeatedly under high ionic strength alkali buffer and acid conditions without altering appreciably its antibody binding capacity. Sequential elution of bound anti-haemagglutinin antibodies with increasing concentrations of sodium iodide has enabled the physical separation of antibody populations with low and high avidity for the virus immunoadsorbent. In haemagglutination inhibition (h1) assays, the less avid population reacted only with the homologous X-31 virus, wheras the more avid antibody population reacted both with the homologous and the related cross-reactive A/England/42/72 (H3N2) strains. Sequential elution under acid conditions did not completely remove the bound anti-haemagglutinin antibodies and those eluted retained little of their anti-haemagglutinin activity. From a practical point of view, given a specific antiserum, it is feasible to use whole virus as an immunoadsorbent for the purpose of isolating populations of antibodies of different avidities and cross-reactivities. Furthermore, sodium iodide as an eluting agent has proved most effective in recovery of active and stable antibodies from the agarosebound virus.
After five months of total isolation a wintering party of seventeen British Antarctic Survey (BAS) personnel was inoculated under double blind concitions with placebo, or rhinovirus type 2 which had been propagated in tissue culture. The clinical and virological responses of these subjects were compared with those of volunteers in England who received a similar dose of the same strain. The virus used was apparently partly attenuated for man; at the dosage used its effects in England were similar to a smaller dose of an unattenuated strain, but in the Antarctic it caused relatively severe infections. Both the symptoms and the laboratory evidence of virus infection appeared to be more pronounced in the BAS subjects than in the volunteers in England who received the same challenge. In the former group the infection readily spread to those who were originally given placebo. In the BAS subjects serum antibody titres were well maintained during the isolation period but a significant fall in nasal immunoglobulin concentration was recorded during the 5 months of isolation after the virus challenge. Possible mechanisms for the increased sensitivity to rhinovirus of subjects who have been totally isolated in a small closed community are discussed.
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