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Biomedical subjects

R M Chanock

Publications and source records attributed to R M Chanock.

At least 235 records · Page 13Linked to original sources
PubMed1977

Further characterization of the complementation group B temperature-sensitive mutant of respiratory syncytial virus.

ts-2, a temperature-sensitive and plaque morphology mutant of respiratory syncytial virus and sole representative of complementation group B, was compared with members of the other complementation groups of respiratory syncytial virus (group A [ts-1] and group C [ts-7]). ts-2 was found to be 10- to 1,000-fold more restricted in growth and ability to spread at restrictive temperatures (37, 38, and 39 degrees C) than at the permissive temperature (32 degrees C). In temperature shift-up experiments, the ts defect of ts-1 and other members of complementation group A was found to effect a late function that was required for at least 13 h in the replicative cycle. The ts lesion of ts-7 affected a function early in the replication cycle. In contrast, ts-2 was not temperature sensitive when studied by the shift-up technique. The discrepancy between the ts plaque property and failure to detect temperature sensitivity during the shift-up experiment was resolved when it was shown that ts-2 had a defect in adsorption or penetration or both at the restrictive temperature. Clonal analysis of revertant ts-2 showed a coordinate restoration of ts+ phenotype ans syncytium-forming capacity. It appears that ts-2 has a defect in a protein that is involved in adsorption and/or penetration of virus and is also responsible for cell fusion activity.

Adsorption↗
PubMed1977

A microtiter solid phase radioimmunoassay for detection of the human reovirus-like agent in stools.

The development of a microtiter solid-phase radioimmunoassay for detection of the human reovirus-like (RVL) agent is described. The test is simple to perform and uses small amounts of reagents; a large number of specimens can rapidly be tested in a single test. Both filtered and unfiltered stool suspensions can be employed. The test was as sensitive as immune electron microscopy, and with an appropriate blocking test, was specific for the human RVL agent.

Antibodies, Viral↗
PubMed1976

Human reovirus-like agent as the major pathogen associated with "winter" gastroenteritis in hospitalized infants and young children.

We found a human reovirus-like agent in the stools of 42 per cent of 143 infants and young children hospitalized with acute gastroenteritis between January, 1974, and June, 1975. Half the patients studied by electron microscopy and serologic technics had evidence of infection with the agent. The infection had a seasonal pattern: 59 per cent of those admitted during the cooler months (November to April) shed the agent, with a peak of 78 per cent in December, 1974, and January, 1975, combined. None of the patients admitted during the warmer months (May to October) shed the agent. None of 275 Escherichia coli isolates from 32 patients with diarrhea produced heat-labile enterotoxin, whereas 17 of the 32 had evidence of infection with the reovirus-like agent. In addition, 14 of 40 parents of 37 patients with diarrhea associated with the reovirus-like agent were also infected, but most infectious were inapparent. This agent appears to be the major cause of diarrheal illness in the young during the cooler months.

Acute Disease↗
PubMed1976

Recent advances in the aetiology of viral gastroenteritis.

Studies with the human reovirus-like (HRVL) agnet, also designated rotavirus and duovirus, have revealed that it is a major aetiological agent of diarrhoea of infants and young children in many parts of the world. In a study of patients admitted with a diarrhoeal illness to the Children's Hospital of the District of Columbia in the United States from January 1974 to June 1975, it was found that half of the patients studied by both virus shedding (by electron microscopy) and serological (complement-fixation) techniques demonstrated evidence of infection with the HRVL agent. The temporal distribution of infections with the HRVL agent followed a seasonal pattern with this agent being shed exclusively by patients admitted during the cooler months of the year. Electron microscopic examination of stools was as efficient as serological methods for detecting infection with the HRVL agent. We also initiated studies to determine the possible mode of transmission of the HRVL agent by studying contacts of hospitalized patients. We found that 35% parents of patients with HRVL infections were also infected with the HRVL agent. Serological studies revealed that the HRVL agent was antigenically related to the Nebraska Calf Diarrhoea Virus, the epizootic diarrhoea of infant mice virus, the SA-11 virus, and the "O" agent.

Animals↗
PubMed1976

Induction of diarrhea in colostrum-deprived newborn rhesus monkeys with the human reovirus-like agent of infantile gastroenteritis.

Diarrhea developed in five newborn rhesus monkeys (Macaca mulatta) inoculated orally on the first day of life with the human reovirus-like agent of infantile gastroenteritis. Incubation period ranged from 2-5 days; virus particles were detected in stools in association with illness, and virus shedding lasted between 1 and 3 days. Virus derived from monkeys that developed illness following inoculation was infectious for other monkeys but did not induce diarrhea which could be associated temporally with virus shedding. Viral antigens were also detected in tissues of the grossly abnormal small intestine of an acutely-ill monkey. Serum antibody responses were demonstrated in two of the ill animals by complement-fixation and/or immunofluorescence.

Age Factors↗
PubMed1976

Experimental production of respiratory tract infection with Mycoplasma pneumoniae in rhesus monkeys.

Knowledge of the pathogenesis of pneumonia due to Mycoplasma pneumoniae has been derived primarily from experimental infection of rodents. As part of an effort to establish a model with a closer resemblance to man, three seronegative, young, adult rhesus monkeys (Macaca mulatta) were inoculated with M. pneumoniae (10(7.4) cfu per animal) by oropharyngeal administration of coarse-particle aerosol. Five to six days after exposure of the animals, cultures obtained from the upper respiratory tract were positive for M. pneumoniae. Each animal subsequently developed a serologic response, as determined by complement fixation, complement-mediated killing, and tetrazolium-reduction inhibition techniques. Infection was subclinical, and serial chest roentgenograms failed to disclose pneumonia throughout the course of infection. Blood cell counts and titers of cold agglutinins remained unchanged. Althought M. pneumoniae was recovered from the upper respiratory tract of two monkeys for 50 days, there was no evidence of transmission of infection to cage-mate controls inoculated with broth.

Animals↗
PubMed1976

Temperature-sensitive mutants of influenza A virus. XI. Transfer of ts lesions in the Hong Kong/68-ts-1 [a] virus to the influenza A/Udorn/72 wild type.

The presence of the temperature-sensitive (ts) lesions of complementation-recombination groups 1 and 5 in the Hong Kong/68-ts-1[A] virus was confirmed by genetic analysis of ts recombinants of the Hong Kong/68-ts-1[A] virus and a Udorn/72 wild-type virus. Three classes of Udorn/72-ts recombinants were found. One class possessed both ts genes of the Hong Kong/68-ts-1[A] parent, a second class possessed the ts lesion characteristic of group 1, and a third class possessed the ts lesion of group 5. The Hong Kong/68-ts-1[A] parent and the Udorn/72-ts recombinants exhibited a 10,000-fold or greater restriction of replication in the lungs of hamsters than did the homologous wild-type virus. All isolates from the lungs and nasal turbinates of recipients of two of the four Udorn/72-ts-1[A] recombinants contained only ts virus. These two properties, restricted replication and genetic stability after replication in vivo, suggest that the Udorn/72-ts-1[A] recombinants should be considered for evaluation as vaccines for use in humans.

Animals↗
PubMed1976

Growth and genetic stability of the ts-1 mutant of respiratory syncytial virus at restrictive temperatures.

An in vitro study was performed to define in greater detail those factors which favored the growth of the ts-1 mutant of respiratory syncytial virus under restrictive conditions and the emergence of genetically altered virus with decreased temperature sensitivity. Replication of ts-1 occurred at each of the restrictive temperatures of 37, 38, and 39 C, even through plaque formation was not observed. The level of virus growth under restrictive conditions was inversely related to the incubation temperature and directly related to the multiplicity of infection. These relationships appeared to reflect the effect of restrictive temperature in reducing the quantity of virus produced and released from an infected cell. Under restrictive conditions the production of genetically altered virus which exhibited reduced temperature sensitivity was directly related to the multiplicity of infection and inversely related to temperature. Production of genetically altered virus was not observed under permissive conditions.

Animals↗
PubMed1976

Cell-mediated immunity to respiratory syncytial virus induced by inactivated vaccine or by infection.

Transformation and increased mitotic activity in donor lymphocytes exposed to specific antigens is considered by many to be a manifestation of cell-mediated immunity. In attempts to understand the apparent "sensitization" of individuals to respiratory syncytial virus (RSV) as a result of receiving inactivated RSV vaccine, in vitro lymphocyte transformation studies were carried out on infants who had received inactivated RSV vaccine and on infants who had received a similarly prepared inactivated African green monkey kidney (AGMK) cell-grown parainfluenza type 1 virus vaccine or a trivalent parainfluenza vaccine prepared in hen's eggs. Each group included some infants who had, and others who had not, undergone natural RSV infection under our observation before the lymphocyte studies. Lymphocytes were studied from 21 infants and young children who had received the inactivated RSV vaccine, 14 who had received a similarly prepared inactivated parainfluenza 1 vaccine, and 5 who received a trivalent parainfluenza vaccine. Twelve of the RSV vaccinees and 14 of the parainfluenza vaccinees had been naturally infected with RSV as indicated by virus recovery and/or antibody rise between the time of vaccination and the lymphocyte studies. In comparing the arithmetic mean for RSV-specific transformation and mitotic activity there was a significant difference between RSV vaccinees and parainfluenza vaccinees whether one compared those who had undergone natural RSV infection or those who had not undergone natural infection. The difference between RSV vaccinees who had not undergone natural RSV infection and RSV-infected parainfluenza vaccinees also was significant. There was a greater level of transformation and mitotic activity in those who had experienced natural infection than those who had not among both RSV vaccinees and parainfluenza vaccinees, but these differences were not significant statistically.

Child, Preschool↗
PubMed1976

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↗
PubMed1976

Antigenic relationships among five reovirus-like (RVL) agents by complement fixation (CF) and development of new substitute CF antigens for the human RVL agent of infantile gastroenteritis.

The human reovirus-like (HRVL) agent, Nebraska calf diarrhea virus (NCDV), epizootic diarrhea of infant mice (EDIM) virus, simian agent (SA)-11, and the "O" (offal) agent were found to be similar, if not identical, in reciprocal complement fixation (CF) tests employing hyperimmune animal sera. In addition, in CF tests with paired sera from 35 diarrhea patients who shed the HRVL agent, 74% developed serologic evidence of infection with the HRVL antigen, 43% with NCDV, 51% with EDIM virus, 57% with SA-11, and 71% with the "O" agent. Thus, in addition to the NCDV, which had previously been described as a suitable substitute CF antigen for the HRVL agent, the SA-11, "O", and EDIM viruses may also be utilized as substitute antigens for the HRVL agent. However, the "O" agent appears to be the most efficient of the four substitute CF antigens and thus should be used preferentially when the HRVL agent is not available. The "O" agent was about as efficient as the HRVL agent and significantly more efficient than the NCDV for detecting seroresponses. The greatest efficiency for detecting infection with the HRVL agent resulted when sera were tested with both the HRVL and "O" agents as 31 (89%) of the patients developed serologic evidence of infection with one or both antigens. The finding of additional substitute CF antigens for the HRVL agent may have implications in the immunoprophylaxis against human disease.

Animals↗
PubMed1976

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↗
PubMed1976

Nonbacterial gastroenteritis.

Significant progress has been made toward determining the agents of acute, infectious, nonbacterial gastroenteritis. Two distinct types of viruses have been implicated. One of these, a particle about 27 nm in diameter, is involved in the acute epidemic form of the disease of short duration. The other, a 70-nm virus, is rarely involved in acute epidemic gastroenteritis, but it has been associated worldwide with infantile diarrhea and is responsible for a considerable proportion of all nonbacterial diarrheal illness in infants. Experiments with the 70-nm virus have induced disease in newborn piglets, calves, and rhesus monkeys. In addition, this human virus has been antigenically related to four other viruses, three of which cause gastroenteritis in their natural animal host.

Animals↗