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Biomedical subjects

R B Belshe

Publications and source records attributed to R B Belshe.

141 records · Page 8Linked to original sources
PubMed1978

Evaluation of five temperature-sensitive mutants of respiratory syncytial virus in primates: II. Genetic analysis of virus recovered during infection.

Five temperature-sensitive (ts) mutants of respiratory syncytial (RS) virus (ts-1, ts-1 NG-1, ts-1 NG-16, ts-2, and ts-7), previously evaluated forinfectivity and virulence in chimpanzees and owl monkeys, were also assayed for in vivo genetic stability. None of the five mutants tested was completely stable genetically. Thus, virus which had lost some or all of the ts property was recovered from each infected chimpanzee. Significantly, each ts-1 NG-1 isolate retained some degree of temperature sensitivity and hence was not true wild-type virus. Clonal analysis of viruses shed by ts-1, ts-1 NG-1, ts-1 NG-16, or ts-7 infected chimpanzees indicated that in most instances only a minority of the virus shed was altered genetically. Of five chimpanzees infected with the ts-2 mutant, three shed only ts virus, and the remaining two chimpanzees shed only ts+ virus. Such ts+ virus proved to be avirulent when evaluated in chimpanzees or owl monkeys, indicating that loss of the ts property did not restore virulence. Based upon these findings, the ts-2 mutant appears to be a suitable candidate for clinical trials in man.

Animals↗
PubMed1978

Growth and genetic stability of 4 temperature sensitive (ts) mutants of respiratory syncytial (RS) virus in newborn ferrets.

Four temperature sensitive (ts) mutants of respiratory syncytial (RS) virus were evaluated for growth and genetic stability in newborn ferrets. ts-1, the mutant previously tested in children as a possible live virus vaccine and found to be insufficiently attenuated for the upper respiratory tract, grew in the lungs of newborn ferrets to the same peak titer as wild type RS virus. In addition some genetic alteration of the ts-1 mutant occurred. Two more defective subclones of ts-1, ts-1 NG-1 and ts-1 NG-16, were greatly restricted in growth in the ferret's lungs. ts-1 NG-16 was also restricted in the nasal turbinates, but ts-1 NG-1 grew to high titer in the nasal turbinates. Growth of ts-1 NG-1, however, was delayed 2 weeks compared to the growth of wild type virus. Genetic alteration occurred during growth of either subclone; the virus isolated was intermediate between wild type and input virus in plaque forming ability at restrictive temperatures. In no instance was wild type virus isolated from the ferrets infected with either subclone. ts-2, a plaque morphology mutant that does not fuse cells to form syncytia even at the permissive temperature of 32 degrees C, was restricted in growth in both the lungs and nasal turbinates, and genetically altered virus was not recovered from these animals. Of the mutants tested, ts-2 was the most restricted mutant in the newborn ferret and should be evaluated further as a candidate vaccine virus.

Animals↗
PubMed1978

Enzyme-linked immunosorbent assay for measurement of serological response to respiratory syncytial virus infection.

An enzyme-linked immunosorbent assay was applied to the detection of serum antibodies against respiratory syncytial virus. The end points of the various sera tested in the assay were approximately 100 times higher than in the complement-fixation test and 2 to 4 times higher than in the plaque reduction test. In addition, the immunosorbent assay appeared to be more efficient than the plaque reduction and complement-fixation techniques for detecting a serological response in young infants (1 to 6 months old) with serous respiratory syncytial virus lower respiratory disease. The simplicity, sensitivity, and rapidity of the enzyme-linked immunosorbent assay make it a useful tool for immunological studies with respiratory syncytial virus.

Antibodies, Viral↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1977

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↗
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↗
PubMed1976

A review of adenoviruses in the etiology of acute hemorrhagic cystitis.

In a comparison of children with acute hemorrhagic cystitis it was noted that 51 per cent of those in Sendai, Japan and 23 per cent of those in Chicago, Illinois had adenoviruria during their illness. These 2 populations are the only ones in which the disease has been studied and reported. In both populations male outnumbered female patients, with a ratio of 3.4 to 1 in Japanese children and 2.3 to 1 in American children. Adenovirus type 11 was isolated exclusively in both studies, with the exception of 2 American children who had adenovirus type 21 in the urine. While the Japanese children experienced their illnesses for approximately 2 weeks American children had symptoms for only 4 to 5 days. Virus shedding continued throughout the illness in both populations. The adenovirus 11 strains from American children were antigenically similar to the prototype adenovirus type 11 strain as measured by cross hemagglutination-inhibition procedures. Adenovirus antigen was identified by immunofluorescence in exfoliated bladder epithelial cells from patients with acute hemorrhagic cystitis. Studies to date indicate that adenovirus type 11 is the etiologic agent in some but not all pediatric cases of acute hemorrhagic cystitis.

Acute Disease↗
PubMedDate not supplied

Male genital tuberculosis: a review of the literature with instructive case reports.

The prevalence of extrapulmonary tuberculosis, including cases at male genital sites, has remained relatively constant during the past two decades in the United States. The most common genital sites of tuberculous infection are the epididymis and prostate; the testicle is infected in a lower proportion of cases. The usual modes of genital involvement include descending infection from the kidneys, intracanalicular or direct extension from neighboring foci in the genital tract, and hematogenous seeding. Local symptoms are usually insidious and progressive. Systemic manifestations such as fever, chills, and sweats are infrequently present in isolated genital tuberculosis. Tuberculous genital infection can be confused with other bacterial (including nontuberculous mycobacterial) infections, fungal disease, tumors, and cysts as well as with a number of less common illnesses. Although some diagnostic and therapeutic indications for surgical excision still exist, the preferred approach to treatment is primarily multiple-drug antituberculous chemotherapy.

Age Factors↗