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Biomedical subjects

D A Tyrrell

Publications and source records attributed to D A Tyrrell.

At least 73 records · Page 4Linked to original sources
PubMed1987

A 'new' generation of more potent synthetic antirhinovirus compounds: comparison of their MICs and their synergistic interactions.

A 'new' generation of synthetic antirhinovirus compounds has recently become available for in vitro evaluation. Thus a new group of compounds from Janssen was found to be 10-fold more active than enviroxime or 57-fold more active than dichloroflavan (DCF), against human rhinovirus 9 (HRV-9). In addition, they were also some 5- and 10-fold more potent than enviroxime and DCF, respectively, against HRV-2. Similarly, a 'new' series of antirhinovirus compounds from Roche, although as active as enviroxime against HRV-9, were found to be 4-fold more potent than DCF against the same virus. Moreover, they were 45- and 90-fold more active than enviroxime and DCF, respectively, when tested against HRV-2. We found that generally HRV-2 was more sensitive to these new compounds than HRV-9. In this study we also report on the synergistic interaction between these new synthetic substances and also with some of the earlier compounds such as DCF and enviroxime and we discuss the possible implication of this synergistic activity regarding the future prevention and treatment of common colds caused by rhinoviruses.

Antiviral Agents↗
PubMed1987

Studies of rhinovirus resistant to an antiviral chalcone.

During studies of the antiviral activity of chalcone Ro-09-0410 on human rhinovirus type 9 (RV9) chalcone-resistant strains of RV9 were isolated and appeared with a frequency of about 10(-5) in chalcone sensitive stock. Chalcone-dependent viruses were found after further passage. Some characteristics of the resistant viruses were studied and compared with those of the wild type virus; a number of differences were detected. They produced smaller plaques and grew to lower titre; they were no longer protected by chalcone from inactivation by heat and low pH. The event responsible for drug dependence apparently took place after that responsible for drug resistance. Drug-resistant viruses were still sensitive to dichloroflavan and enviroxime.

Antiviral Agents↗
PubMed1987

Sequential infection or immunization of ferrets with a series of influenza A (H3N2) strains (report to the Medical Research Council's Sub-Committee on influenza Vaccines (CDVIP/IV)).

Previous studies of boys at Christ's Hospital school have indicated that annual immunization with influenza virus vaccines did not significantly reduce the total incidence of influenza infection compared to unimmunized subjects. In view of the implications of this result, a similar study was conducted in ferrets to clarify these findings. Groups of ferrets were immunized or infected with a series of influenza A (H3N2) viruses over an 18-month period, and the immunity to subsequent live virus challenge was measured after each virus or vaccine exposure. The results indicated that live virus infection gave a more solid immunity than immunization with inactivated vaccine; and the serum haemagglutination-inhibiting antibody response was greater following immunization than following infection. In addition, differences in immunity could not be explained by measurements of cross-reacting and specific antibody, since the incidence of these antibodies was similar in both infected and immunized animals. The results do not suggest an explanation for the different levels of immunity induced following infection or immunization or the results obtained from the Christ's Hospital study. However, the relative contribution of various immune responses to virus or virus antigen is discussed, and it is suggested that the difference in immunity may lie in the ability of live virus infection to stimulate local antibody.

Animals↗
PubMed1987

Intranasal chalcone, Ro 09-0410, as prophylaxis against rhinovirus infection in human volunteers.

The antirhinovirus agent chalcone Ro 09-0410 was tested in double-blind place-controlled volunteer trials for its protective efficacy against experimental rhinovirus infection. Fifty volunteers received either drug (26 volunteers) or placebo (24 volunteers) both before and after challenge with 20-40 tissue culture infecting dose (TCID50) of human rhinovirus 2 (RV2). There was no evidence that medication significantly reduced the incidence of infection or illness, indeed there was some increase in the nasal secretion produced.

Administration, Intranasal↗
PubMed1987

Prophylaxis and treatment of rhinovirus colds with zinc gluconate lozenges.

Following a tolerance study, double-blind placebo controlled trials were conducted to determine the prophylactic effect of zinc gluconate lozenges on rhinovirus challenge and, in a third study, their therapeutic efficacy when given at the start of colds caused by virus inoculation was tested. In the prophylaxis study a total of 57 volunteers received lozenges of either zinc gluconate (23 mg) (29 volunteers) or matched placebo (28 volunteers) every 2 h while awake during a period of four and a half days. They were challenged with 10(2) tissue culture infecting dose (TCID50) of human rhinovirus 2 (HRV-2) on the second day of medication, and were monitored daily for symptoms and signs of colds and laboratory evidence of infection. Zinc reduced the total mean clinical score from 8.2 in the placebo group to 5.7 and the reduction of the mean clinical score was statistically significant on the second day after virus challenge. In the therapeutic study 69 volunteers were inoculated with 10(2) TCID50 of HRV-2 and those who developed cold symptoms were randomly allocated to receive either zinc gluconate lozenges (six volunteers) or matched placebo lozenges (six volunteers) every two hours they were awake for six days. Treatment of colds with zinc reduced the mean daily clinical score and this was statistically significant on the fourth and fifth day of medication. Similarly, medication also reduced the mean daily nasal secretion weight and total tissue count and these reductions were statistically significant on days two and six for nasal secretion weights and days four to six of medication for tissue counts when compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Selective effects of minor illnesses on human performance.

The study reported here examined the effects of experimentally induced minor illnesses (colds and influenza) on the efficiency of human performance. Influenza impaired the ability to detect and respond quickly to stimuli appearing at irregular intervals, but had no effect on a task requiring hand-eye coordination. In contrast to this, colds impaired hand-eye coordination but had little effect on the detection tasks. These results are of great practical importance because many skills clearly involve both attentional and motor factors and are, therefore, likely to be impaired by minor illnesses. The findings are also of major theoretical interest because of the dissociation of psychological functions produced by the different types of illness.

Achievement↗
PubMed1987

Effects of experimentally induced respiratory virus infections and illness on psychomotor performance.

In two studies experimentally induced colds slowed the speed of response in a serial reaction task. Responding was also slower during the incubation period of the illness, which shows that performance on such a task may be used to predict subsequent illness. Volunteers who had no significant clinical illness, but who had a significant rise in IgG following virus challenge, also showed changes in performance. In contrast to the serial reaction task, neither colds nor subclinical infections impaired performance on a detection task.

Common Cold↗
PubMed1987

Variation of erythroid and myeloid precursors in the marrow and peripheral blood of volunteer subjects infected with human parvovirus (B19).

Infection of normal individuals with human parvovirus (B19) results in a mild disease (erythema infectiosum) but gives rise to aplastic crises in patients with chronic hemolytic anemias. The effects of this disease on hemopoiesis were investigated following intranasal inoculation of the virus into three volunteers. A typical disease ensued with a viremia peaking at 9 d. Marrow morphology 6 d after inoculation appeared normal but at 10 d there was a severe loss of erythroid precursors followed by a 1-2-g drop in hemoglobin, and an increase in serum immunoreactive erythropoietin. Erythroid burst-forming units (BFU-E) from the peripheral blood were considerably reduced, starting at the time of viremia and persisting for 4-8 d depending on the individual. Granulocyte-macrophage colony-forming units (CFU-GM) were also affected but the loss started 2 d later. Both CFU-GM and BFU-E showed a sharp overshoot at recovery. In the marrow, BFU-E and CFU-E were reduced at 6 and 10 d in the individual having the longest period of peripheral progenitor loss. In contrast, there was an increase in BFU-E and CFU-E in the subject with least change in peripheral progenitors. In the third subject, with an intermediate picture, there was a loss at 6 d but an increase at 10 d of erythroid progenitors. It is suggested that the architecture of the marrow might partially isolate progenitors from high titers of virus in the serum and individual variation in this respect might give the results observed.

Adult↗
PubMed1987

Infectivity and reactogenicity of reassortant cold-adapted influenza A/Korea/1/82 vaccines obtained from the USA and USSR.

The safety and immunogenicity of two live influenza A virus vaccine strains, the CR 59 and 17/25/1 cold-adapted (ca) reassortants, were evaluated in 170 healthy young adult volunteers. The vaccines were produced by recombining A/Korea/1/82 (H3N2) wild-type virus with either A/Ann Arbor/6/60 (H2N2) or A/Leningrad/134/17/57 (H2N2) ca donors of attenuation. Both vaccines were well tolerated in volunteers. The 17/25/1 strain, prepared from A/Leningrad, infected at least 70% of seronegative volunteers after the first dose and 84% after the second; the CR 59 strain infected 62% and 72% of volunteers after first and second doses, respectively. Among the vaccinees who were initially seropositive, 17/25/1 infected 66% after one dose and 85% after two, while CR 59 infected 62% and 71%, respectively. Despite differences in temperature sensitivity, genetic composition, and serological reactivity to monoclonal antibodies, both vaccines behaved almost identically in animal models and man. We conclude that both donors of attenuation may be of great potential value.

Adolescent↗
PubMed1987

Upper respiratory tract viral infection and mucociliary clearance.

Twenty-six normal volunteers were exposed to rhinovirus or influenza B virus. Measurement of nasal mucociliary clearance, ciliary beat frequency, percent of epithelium ciliated, ciliary ultrastructure and nasal transmucosal potential difference were made before exposure, during viral incubation and at the time of expected overt infection. Ten volunteers failed to become infected, six were subclinically infected and nine were infected with symptoms. There were no significant differences between the results in volunteer groups during the incubation period or between uninfected and subclinical groups at the time of expected symptoms. Six of nine symptomatic infected volunteers had prolonged nasal clearance, and six of the seven biopsied had less than 50% of their epithelium ciliated. However, there was no significant reduction in ciliary beat frequency nor increase in ultrastructural ciliary abnormalities within this group of symptomatic volunteers. Of the two symptomatic infected (influenza B) volunteers tested, both showed significantly reduced transmucosal potential difference.

Adult↗
PubMed1986

A major role for viruses in acute childhood encephalopathy.

29 children and 3 adults with acute depression of conscious level or acute onset of focal neurological signs were studied prospectively. 3 were found to have a non-infectious cause for their illness. The presence of interferon or specific antibodies in the serum and/or cerebrospinal fluid provided evidence of active virus infection in 25 of the remaining 29 patients. There was laboratory evidence that a virus had invaded the central nervous system in 11 patients. Early investigation gave the highest diagnostic yield. Since several common viruses were identified, it appears that the nature of the illness is due more to the host response than to the nature of the infective agent.

Acute Disease↗
PubMed1986

Detection of human rhinoviruses and their molecular relationship using cDNA probes.

We describe here a cDNA:RNA hybridization system for the study of human rhinoviruses. We have constructed an M13 probe from the 5' end of the genome of rhinovirus 14 (HRV-14) and used this to detect directly viral RNA. Of the 56 human rhinoviruses so far investigated 54 or 96.4% gave clearly positive hybridization signals. However, the strength of this signal depended very much on the molecular relationship of these viruses. Thus, HRV-3, 4, 17, 72, and, to a slightly lesser extent, HRV-2, 6, 9, 13, 19, 31, 42, 49, 64, and 69 appear to be closely related to HRV-14 whereas HRV-5, 7, 8, 16, 32, 40, 45, 55, 56, 63, 80, 82, and 85 appear to be relatively divergent. Further, evidence is provided in this study that indicates that it would be feasible to use cDNA probes to detect human rhinoviruses in nasal washings. However, the sensitivity of detection was clearly affected by both the inclusion of inhibitors of endogenous RNase activity in the RNA extraction mixture and also in the method of extracting the viral RNA. From reconstruction experiments in nasal washings and under optimal conditions, we can detect virus at 10(2.8) TCID50/ml.

Common Cold↗
PubMed1986

Synergism between anti-rhinovirus antivirals: various human interferons and a number of synthetic compounds.

DCF (dichloroflavan), enviroxime, chalcone Ro-09-0410 and HuIFN (Human interferon)-alpha 2, HuIFN-beta, HuIFN-beta X 401 and HuIFN-gamma, showed antiviral activity in vitro against RV2 (rhinovirus type 2) and RV9. Binary combinations of these drugs showed synergistic activity of which the combinations of HuIFN-gamma or HuIFN-alpha and enviroxime were of most interest. They were studied in more detail in tissue culture by virus yield experiments and in organ culture of human embryonic nasal epithelium and human embryonic tracheal culture in which there was a potent antiviral synergy. These results indicate that such combinations of drugs may be worthy of clinical study.

Antiviral Agents↗