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Biomedical subjects

R M Chanock

Publications and source records attributed to R M Chanock.

At least 217 records · Page 12Linked to original sources

Enzyme-linked immunosorbent assay (ELISA) for detection of human reovirus-like agent of infantile gastroenteritis.

An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of the human reovirus-like agent of infantile gastroenteritis in human stools. The results of the assay can be read either with a simple colorimeter or the naked eye. Investigations with 143 samples from children with gastroenteritis and 75 samples from children with other illnesses showed that the ELISA was as sensitive as electron microscopy or radioimmunoassay for detection of this agent. In addition, the ELISA was simple to perform and, when read visually, did not require sophisticated technical equipment. These advantages make it suitable for field work.

Animals↗

Human reovirus-like agent infection. Occurrence in adult contacts of pediatric patients with gastroenteritis.

Sixty-four adult family contacts of 61 young patients with gastroenteritis were included in a study for evidence of concurrent infection with the human reovirus-like agent (HRVLA) of infantile diarrhea. Evidence of infection was detected in 26 (41%) of the adult contacts. The HRVLA infection occurred significantly more often among adult contacts of pediatric patients infected with HRVLA (55%) than among contacts of young patients not infected with the agent (17%). Mild cases of gastroenteritis developed in only three of the contacts infected with HRVLA.

Adolescent↗

Experimental respiratory syncytial virus infection of four species of primates.

Four species of nonhuman primates were inoculated intranasally with 10(3.1) to 10(3.7) plaque forming units (pfu) of respiratory syncytial (RS) virus. Adults squirrel monkeys and newborn rhesus monkeys became infected and shed small quantities (peak titer 10(2.0) pfu/ml of nasopharyngeal swab specimen) of virus, but illness did not develop. Infant cebus monkeys aged 2 months became infected, shed 10(2.3) to 10(3.8) pfu/ml of nasopharyngeal swab specimen, but did not become ill. Chimpanzees aged 15 to 18 months shed a large quantity of virus, up to 10(6.0) pfu/ml of nasopharyngeal swab specimen and developed an upper respiratory illness. Chimpanzees are proposed as a possible animal model for future study of the immunopathology of RS virus disease and for in vivo evaluation of attenuated live virus vaccine candidates.

Animals↗

Isolation and characterization of further defective clones of a temperature sensitive mutant (ts-1) of respiratory syncytial virus.

After exposure of the temperature sensitive ts-1 mutant of respiratory syncytial virus to the chemical mutagne, nitrosoguanidine (NG), 2 clones of virus were recovered which were more temperature sensitive and stable genetically than the ts-1 mutant. The initial criterion used for selection of the 2 clones was decreased ability to produce plaques at 36 degrees C. Subsequently it was shown that the 2 clones grew less well at the restrictive temperatures of 37 degrees and 38 degrees C than did the ts-1 parent. Peak titers of the NG derived clones were decreased 10--30 fold at 37 degrees C and over 100-fold at 38 degrees C compared to ts-1. Complementation analysis indicated that the NG mutants retained the same complementation pattern as the ts-1 parent.

Cell Line↗

Cold adapted variants of influenza A. II. Comparison of the genetic and biological properties of ts mutants and recombinants of the cold adapted A/AA/6/60 strain.

The genetic and biological properties of 13 recombinant influenza A clones derived at 25 degrees C from the A/AA/6/60-cold variant (by crosses with 4 different wild type strains) were compared with a set of 5-FU induced ts-mutants. The 5-FU mutants had previously been placed into 7 complementation-recombination groups; the A/AA/6/60-cold parent (PI-7) and the 12 cold recombinant clones which were ts were shown to share a lesion with only one of these groups. The parental strain and 5 recombinant clones were evaluated for replication in the lungs and nasal turbinates of hamsters. Each virus appeared to be attenuated; genetic stability correlated with the level of viral replication in the hamster lung, i.e., viruses which grew best showed a tendency to revert to the ts+ phenotype. Characterization of the ts+ revertants for the presence of the cold adaptation property revealed that these viruses exhibited a spectrum of cold adaptation properties. Two viruses, PI-7 (the parental cold variant) and the CR6 recombinant (A/Queensland/6/72) did not revert in either the lungs or nasal turbinates of hamsters.

Animals↗

Clinical features of acute gastroenteritis associated with human reovirus-like agent in infants and young children.

Between January, 1974, and June, 1975, infection with a human reovirus-like agent was detected in 47% of 152 infants and children hospitalized with acute gastroenteritis. Certain epidemiologic, clinical, and laboratory findings appear to be helpful in distinguishing gastroenteritis due to HRVLA from other causes in those children sick enough to require hospitalization. Age: 76% of infants and children seven through 12 months of age and 76% of those 13 through 24 months of age had infection with the HRVLA, whereas such infection was found in only 21% of infants under six months of age and 23% of children 25 through 60 months of age. Time of Year: 61% of patients studied during the cooler months had HRVLA infection and such infection was not found from June to October. Frequency of vomiting and dehydration: Twice as many patients infected with HRVLA as those who were not had vomiting (92%) and significant dehydration (83%).

Acute Disease↗

Detection by immune electron microscopy of 26- to 27-nm viruslike particles associated with two family outbreaks of gastroenteritis.

Viruslike particles 26-27 nm in size were detected by immune electron microscopy in stools of volunteers who were ill after administration of bacteria-free fecal filtrates derived from two separate family outbreaks of acute epidemic nonbacterial gastroenteritis. Fluorocarbon treatment and concentration of the filtrates were necessary to provide enough antigen to test sera by immune electron microscopy. Serum antibody responses were detected in both naturally occurring and experimentally induced cases of illness. The Montgomery County viruslike particle appeared to be related to the previously described Norwalk particle, whereas the Hawaii particle appeared to be unrelated to the Norwalk particle.

Animals↗

Unexpectedly high frequency of antibody to Mycoplasma pneumoniae in human sera as measured by sensitive techniques.

Mycoplasmacidal and radioimmunoprecipitating antibodies to Mycoplasma pneumoniae were commonly detected in healthy children younger than five years of age, in whom natural disease due to M. pneumoniae is rare. Antibody in serum could also be demonstrated in Marine recruits several weeks or months before development of pneumonia due to M. pneumoniae. The latter observation suggests that serum antibody does not confer protection against disease caused by M. pneumoniae.

Adolescent↗

Temperature-sensitive mutants of Streptococcus pneumoniae. I. Preparation and characterization in vitro of temperature-sensitive mutants of type I S. pneumoniae.

After exposure of type I Streptococcus pneumoniae to nitrosoguanidine, 13 temperature-sensitive (ts) mutants were selected that were restricted in capacity to form colonies on blood agar at 38 C. Whereas colony formation by the type I parent (ts+) was unaffected by a temperature of as high as 39 C, the ts mutants exhibited a spectrum of temperature sensitivity in which colony formation was inhibited significantly at 36 C, 37 C, 38 C, or 39 C. Growth of ts mutants at 38 C in broth was reduced or delayed relative to that of ts organisms under identical conditions. In general, there was a direct correlation between degree of temperature sensitivity and genetic stability. Mutants grown at a permissive temperature resembled the ts+ type I parent in colonial morphology and properties of alpha-hemolysis, bile solubility, optochin sensitivity, and antibiotic sensitivity. Moreover, in vitro studies indicated that the mutants retained capsules of immunochemically reactive type I capsular polysaccharide.

Bile↗

Temperature-sensitive mutants of influenza A virus. XIV. Production and evaluation of influenza A/Georgia/74-ts-1[E] recombinant viruses in human adults.

The two temperature-sensitive (ts) lesions present in influenza A/Hong Kong/68-ts-1[E] (H3N2 68) virus were transferred via genetic reassortment to influenza A/Georgia/74 (H3N2 74) wild-type virus. A recombinant clone possessing both ts lesions and the shutoff temperature of 38 C of the Hong Kong/68 ts donor and the two surface antigens of the Georgia/74 wild-type virus was administered to 32 seronegative adult volunteers. Thirty-one volunteers were infected, of whom only five experienced mild afebrile upper respiratory tract illness. The wild-type recipient virus was a cloned population that induced illness in five of six infected volunteers. Therfore, the attenuation exhibited by the Georgia/74-ts-1[E] virus could reasonably be assumed to be due to the acquisition of the two ts-1[E] lesions by the Georgia/74 wild-type virus. The serum and nasal wash antibody responses of the ts-1[E] vaccinees were equivalent to those of the volunteers who received wild-type virus. The two ts lesions present in the Hong Kong/68-ts-1[E] virus have now been transferred three times to a wild-type virus bearing a new hemagglutinin, and in each instance the new ts recombination exhibited a similar, satisfactory level of attenuation and antigenicity for adults. It seems likely that the transfer of the ts-1[E] lesions to any new influenza virus will regularly result in attenuation of a recombinat virus possessing the new surface antigens.

Animals↗

Temperature-sensitive mutants of type I Streptococcus pneumoniae: preparation, characterization, and evidence for attenuation and immunogenicity.

Thirteen temperature-sensitive (ts) mutants of type I Streptococcus pneumoniae were selected after exposure of virulent wild-type (ts+) organisms to nitrosoguanidine. Each mutant resembled the ts+ parent in properties of alpha-hemolysis, bile solubility, optochin sensitivity, antibiotic sensitivity, and serotype. Unlike the ts+ parent, however, each ts mutant was restricted in its capacity to form colonies on blood agar at 38 C. With the exception of two mutants, there was a correlation between the degree of temperature-sensitivity of a mutant and its genetic stability. When inoculated intraperitoneally into mice, 11 of 13 mutants were attenuated and induced homologous resistance. Three mutants (ts 1, ts 3, and ts 4) were also studied in hamsters and were found to be attenuated and immunogenic after intraperitoneal injection. Study of the behavior of mutants ts 1, ts 3, and ts 4 in the blood of hamsters suggested that attenuation may be related, in part, to decreased growth and survival of ts organisms at body temperature. Mutants ts 1 and ts 4 were completely attenuated for hamsters when administered intranasally and induced significant resistance to subsequent challenge with wild-type organisms by the same route. Local administration of ts mutants of type 1 S. pneumoniae to hamsters may provide a model for evaluating the potential of live vaccines in the prevention of disease due to bacterial respiratory tract pathogens.

Animals↗

Safety and antigenicity of inactivated influenza virus vaccines in children: trials with monovalent and bivalent A/New Jersey/76 (HswN1) and A/Victoria/75 virus vaccines in Washington, D.C..

Safety and antigenicity of monovalent and bivalent A/New Jersey/NJ)/76 (HssN1) and A/Victoria/75 inactivated influenza virus vaccines were studied in 125 children aged three to 18 years. In recruitment, families who knew the study team, who were professionally involved, and/or who were under close continuing care were more likely to volunteer for such studies than those who were unfamiliar with the team or institution. Antibody responses and systemic reactions occurred more often after administration of inactivated whole-virus vaccine than after split-virus vaccine. Significant titers (greater than or equal to 1:40) of hemagglutination-inhibiting antibody to A/NJ/76 virus occurred in 95% of normal children three to 18 years of age who received two doses of the same vaccine (whole or split). However, insufficient numbers of children achieved a reasonable antibody titer (greater than or equal to 1:40) after one dose of vaccine.

Adolescent↗

Immunoprophylaxis of experimental Mycoplasma pneumoniae disease: effect of route of administration on the immunogenicity and protective effect of inactivated M. pneumoniae vaccine.

Formalin-inactivated Mycoplasma pneumoniae vaccine was administered subcutaneously or intranasally to hamsters to examine the effect of route of administration on immunogenicity and protective effect. Parenterally administered vaccine in the doses employed induced serum complement-fixing antibody formation, but did not significantly decrease the frequency of pneumonia following challenge with virulent M. pneumoniae. Intranasally instilled vaccine was ineffective in stimulating serum antibody, but did diminish the frequency of experimentally induced pneumonia due to M. pneumoniae. However, a greater degree of resistance was induced by intranasal infection with either wild-type organisms or the ts 640 attenuated mutant of M. pneumoniae.

Administration, Intranasal↗

Immunoprophylaxis of experimental Mycoplasma pneumoniae disease: effect of aerosol particle size and site of deposition of M. pneumoniae on the pattern of respiratory infection, disease, and immunity in hamsters.

The distribution of Mycoplasma pneumoniae infection in the respiratory tract and the extent of pulmonary pathology were determined by the site of deposition and the number of organisms administered to hamsters. Infection of the upper and lower areas of the respiratory tract occurred when organisms were introduced into both areas by small-particle aerosol (2.3 micrometer) or by intranasal (i.n.) instillation of a 200-microliter inoculum. In contrast, when organisms were delivered primarily to the upper respiratory tract by large-particle aerosol (8 micrometer) or by i.n. instillation of a small volume of inoculum (2 or 20 microliter), infection remained limited to this area in most or all instances. When the lungs became infected after i.n. administration of a 200-microliter inoculum, the most extensive pulmonary lesions were seen in the animals given the largest number of organisms. Each of the modes of administration of M. pneumoniae initiated an infection which conferred measurable resistance to a subsequent challenge capable of inducing extensive pulmonary disease. The most effective resistance was induced by the two modes of administration which produced an infection involving the entire respiratory tract, i.e., small-particle aerosol or i.n. instillation of a 200-microliter inoculum.

Administration, Intranasal↗

Use of a free viral immunofluorescence assay to detect human reovirus-like agent in human stools.

Human reovirus-like agent (HRVLA) is a major cause of gastroenteritis in infants and young children in many parts of the world. Detection of HRVLA in stools is impractical with the techniques currently available. We describe a rapid immunofluorescence assay for detection of HRVLA in stools. Results with this assay agreed well with results obtained from examination of stool specimens by electron microscopy.

Animals↗

Microtiter solid-phase radioimmunoassay for detection of Escherichia coli heat-labile enterotoxin.

The development of a microtiter solid-phase radioimmunoassay for the detection of Vibrio cholerae enterotoxin and heat-labile Escherichia coli enterotoxin is described. The test is based on the immunological similarity between V. cholerae toxin and E. coli heat-labile toxin. The assay is easy to perform, quantitative, and at least as sensitive and specific as the Y-1 adrenal cell system.

Adrenal Glands↗