PubMed Health⌕ Search

Biomedical subjects

B R Murphy

Publications and source records attributed to B R Murphy.

At least 289 records · Page 16Linked to original sources

Three strains of influenza A virus (H3N2): interferon sensitivity in vitro and interferon production in volunteers.

Three antigenic variants of the H3N2 subtype of wild-type influenza A virus (representing the years 1968, 1972, and 1974) were examined for their sensitivity to interferon and for their ability to induce local respiratory tract interferon in volunteers. In addition, the time of appearance of symptoms in infected volunteers was correlated with the patterns of virus shedding and interferon production. The sensitivity to interferon and the ability to stimulate nasopharyngeal interferon were similarly high for all three strains. Symptomatic illness, peak virus shedding, and peak interferon response all occurred within a 26-h period. These findings imply that interferon or its inducers theoretically could be protective if applied prophylactically, but would be less efficacious when used therapeutically.

Adult↗

Evaluation of a temperature-sensitive influenza virus in elderly and chronically ill subjects.

A temperature-sensitive influenza virus, influenza A/Hong Kong/68-ts-1 (E), was administered to 18 elderly subjects and to 18 chronically ill subjects. Clinical reactions were infrequent (n = 3), mild, and afebrile. Vaccine virus was recovered from 5 subjects. Serum-neutralizing antibody responses to A/Hong Kong/68 antigen were detected in 13. Serum hemagglutination inhibiting antibodies were detected in 6 to A/Hong Kong/68 antigen and in 7 to A/England/42/72 antigen. Nasal antibodies were detected in 3. Using any criteria, a total of 17 patients developed evidence of infection, and occurrence of infection was related to concentration of serum antibody before inoculation. Transmission of vaccine virus may have occurred to one of 10 uninoculated subjects. In the presence of a naturally occurring outbreak of influenza A/England/42/72, 15 ts-1 (E) vaccines and 17 of 42 persons who had received parenteral vaccine became ill. Evidence of infection with influenza virus was obtained in 8 of the former and 10 of the latter group.

Adult↗

Temperature-sensitive mutants of influenza A virus: response of children to the influenza A/Hong Kong/68-ts-1(E) (H3N2) and influenza A/Udorn/72-ts-1(E) (H3N2) candidate vaccine viruses and significance of immunity to neuraminidase antigen.

One of two slightly different influenza A/ts-1[E] recombinant candidate live vaccines was given intranasally to each of 23 young children. Twelve of 15 children who had no serum HI antibody but who did have serum ANAB at the time of administration became infected and 1 had mild rhinitis. All eight who lacked both types of antibody became infected and they shed virus in higher titer and for longer than the former group; five had rhinorrhea and five had mild fever. These findings suggest that serum ANAB plays a part in modulating influenza virus infection and that the full expression of virulence of these or other attenuated influenza vaccines may be manifest only in individuals lacking both HI antibody and ANAB. These particular candidate vaccine strains appear to be attenuated for older children (who have some prior experience with influenza A as demonstrated by serum ANAB), but the occurrence of fever in over half who had no prior experience indicates that they would not be acceptable for a vaccine in wide-spread use.

Antibodies, Viral↗

Temperature-sensitive mutants of influenza A virus. XII. Safety, antigenicity, transmissibility, and efficacy of influenza A/Udorn/72-ts-1[E] recombinant viruses in human adults.

The influenza A/Hong Kong/68-ts-1[E] virus (shutoff temperature, 38 C), which possesses many characteristics desirable in a vaccine virus, was used as a donor of its two temperature-sensitive (ts) lesions to the antigenically divergent influenza A/Udorn/72 wild-type virus. Two subsets of Udorn/72-ts-1[E] recombinant viruses were evaluated in seronegative volunteers (serum titer of hemagglutination-inhibiting antibody, less than or equal 1:8). The first subset, represented by clone 13, possessed a shutoff temperature of 39 C and only one of the two ts lesions; this virus was insufficiently attenuated for use in humans. The other subset, represented by clones 16 and 24, possessed both ts lesions and a shutoff temperature of 38 C, like that of its Hong Kong/68-ts-1[E] parent. This subset, also like its ts-1[E] parent, was adequately attenuated, nontransmissible, and protective against intranasal challenge with wild-type Udorn/72 virus. The attenuation manifested by the ts mutants was not a result of their cloning in bovine kidney tissue or replication in eggs. The results suggest that the Hong Kong/68-ts-1[E] virus can be considered for use as a master strain for donation of ts lesions and thus could bring about predictable attenuation of new wild-type influenza A viruses.

Antibodies, Viral↗

Attenuated influenza virus in normal adults: role of pulmonary function studies in vaccine trials.

A live attenuated virus, influenza A/Hong Kong/68(H3N2)-ts-1[E], was administered to 10 normal volunteers. Infection resulted in minor upper respiratory tract symptoms in one volunteer. An isolate from one volunteer contained a presumed revertant wild-type virus, but no clinical significance could be ascribed to this infection. Since infection with natural influenza A virus adversely affects airway dynamics, serial tests of pulmonary function were performed, including measurements of forced expiratory flow rates, lung volumes, diffusing capacity, closing volume, and total pulmonary resistance at various frequencies by the oscillometric technique. All tests performed before and on days 3, 30, and 60 after administration of virus yielded normal results throughout the study; these results suggested that there was no inflammatory response to the candidate vaccine in either the large or the small airways. Determination of total pulmonary resistance by the oscillometric technique proved to be a simple and acceptable procedure and may be useful in large-scale epidemiologic studies.

Adult↗

Animal model for determining the no-effect level of an antimicrobial drug on drug resistance in the lactose-fermenting enteric flora.

Mature beagles were fed a ground-meal diet containing 0, 2, or 10 mug of oxytetracycline per g for 44 days. The 10-mug/g diet resulted in a shift from a predominantly drug-susceptible population of enteric lactose-fermenting organisms to a multiply antibiotic-resistant population which peaked at 78% resistant organisms. Since a shift to drug-resistant organisms did not occur in the group fed 2 mug/g, the level of oxytetracycline that results in increased incidence of antibiotic resistance lies between 2 and 10 mug/g in this dog model. Rats and hamsters fed diets containing oxytetracycline (10 mug/g or greater) or dihydrostreptomycin (10 mug/g), and provided suspensions of drug-susceptible Escherichia coli, did not develop a population of antibiotic-resistant organisms.

Animals↗

Failure of attenuated temperature-sensitive influenza A (H3N2) virus to induce heterologous interference in humans to parainfluenza type 1 virus.

The present investigation was undertaken to determine if a candidate live vaccine virus, influenza A/Hong Kong/68-ts-1 [E] (H3N2), induced heterologous interference against an interferon-sensitive, wild-type, parainfluenza type 1 challenge virus. The parainfluenza virus was administered 7 days after Hong Kong/68-ts-1 [E] virus infection. The clinical response, daily quantitative virus shedding, interferon production, and serum and nasal wash antibody responses were determined in an experimental group (influenza A virus followed by parainfluenza virus) and 10 volunteers in a control group (parainfluenza virus only). The volunteers were selected on the basis of susceptibility to the two viruses, i.e. serum hemagglutination-inhibition antibody titer of is less than or greater to 1:8 for influenza virus and low nasal wash antibody titer (is less than or greater to 1:8) for parainfluenza virus. Despite a 100% infection rate in the Hong Kong/68-ts-1 [E] vaccinees, no heterologous interference was induced against the parainfluenza type 1 virus challenge.

Animals↗

Determination of influenzavirus neuraminidase inhibition titres.

Representatives of the WHO influenza programme recently proposed a standard method of determining neuraminidase activity and neuraminidase inhibition (NI) antibody titres. Logit transformation of the data obtained with the WHO method for the NI assay permits a more efficient performance of the test and easy calculation of titres with a computer programme.

Antibodies↗