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Biomedical subjects

S R Mostow

Publications and source records attributed to S R Mostow.

At least 37 records · Page 2Linked to original sources
PubMed1979

Adverse effects of lidocaine and methylparaben on tracheal ciliary activity.

The effect of standard concentrations of lidocaine HCl and methylparaben (preservative) on the ciliary activity of ferret tracheal rings in organ culture was assessed. Pure lidocaine concentrations as low as 0.5% caused complete ciliostasis which was reversible after removal of the drug. One percent and two percent effects were not completely reversible. Pure methylparaben concentrations as low as 0.06 mg/ml paralyzed cilia; and, at concentrations of 0.5 mg/ml or higher, adverse effects were not completely reversible. When lidocaine and methylparaben were combined at the same ratio used in commercial preparations, their ciliotoxic effects were additive. These data suggest that topical respiratory anesthesia may result in prolonged ciliary paralysis.

Animals↗
PubMed1979

Behavior of vaccine revertants of temperature-sensitive mutants of influenza virus in ferret tracheal organ culture.

A live attenuated influenza vaccine candidate was not genetically stable when administered to some children who lacked antibody to surface proteins of the virus. To obtain additional biological information about these revertants, the vaccine strain, the wild-type parental strain, and isolates recovered from inoculated children during a vaccine trial were evaluated in ferret tracheal organ culture for effects on the ciliated epithelium and replication at both permissive and restrictive temperatures. The studies revealed that the vaccine strain destroyed cilia and replicated to high titer at its permissive temperature (33 degrees ) but caused minimal damage and replicated to very low titer at its restrictive temperature (37 degrees C). The wild-type parent destroyed cilia at both 33 and 37 degrees C. Isolates which were no longer temperature sensitive (ts(+)) destroyed cilia at both restrictive and permissive temperatures and grew to high titer. Isolates which retained the ts phenotype behaved as the vaccine strain in this system. The ts(+) virus recovered from volunteers behaved like the wild-type parent, which suggests that these viruses had not merely lost their ts phenotype, but had undergone reversion to wild type. Important information about the genetic stability of temperature-sensitive influenza vaccine strains recovered from volunteers can be obtained by evaluating them in ferret tracheal organ culture.

Animals↗
PubMed1979

Sulfhydryl-mediated depression of ciliary activity: an adverse effect of acetylcysteine.

Although N-acetyl-L-cysteine (Mucomyst) is an effective mycolytic, numerous investigations have failed to demonstrate a consistent improvement in pulmonary mechanics following its use. In order to determine whether its beneficial mucolytic activity might be counterbalanced by a deleterious direct effect on cilia, we studied its effect on the activity of ciliated epithelium in the ferret tracheal organ culture system. N-acetyl-L-cysteine consistently caused progressive time-dependent ciliostasis at concentrations clinically employed, with complete ciliary paralysis within 8 hr. The effect was only partially reversed by the removal of the drug. Control preparations retained full ciliary activity for 3 to 12 weeks. In order to determine the active site on the N-acetyl-L-cysteine molecule, we investigated the ciliostatic effects of five of its chemical analogs. Isomolar N-acetyl-L-alanine was not ciliostatic, indicating the necessity of a sulfhydryl group for activity. Ciliostasis was independent of isomeric structure, acetylation, and chain length, as evidenced by the similar ciliostatic effects of L-cysteine, D-cysteine, 2-mercaptoethylamine, and N-acetyl-L-homocysteine. We conclude that N-acetyl-L-cysteine induces partially reversible ciliostasis of tracheal epithelium via its sulfhydryl group; prolonged use of this drug may impair mucociliary clearance.

Acetylcysteine↗
PubMed1978

Behavior of respiratory syncytial virus in piglet tracheal organ culture.

Piglet tracheal organ cultures were infected with respiratory syncytial virus (RSV) and observed for 21 days. Light and immunofluorescence microscopy demonstrated destruction of the ciliated epithelial cells and the presence of viral antigens in the epithelium. Virus was shed in high titer for 12--19 days. Ciliostasis could be quantitated, and it was shown that several strains of RSV grew and damaged tracheal organ cultures in a similar fashion. A temperature-sensitive mutant of RSV, ts-1, was examined at permissive (33 C) and restrictive (37 C) temperatures. This mutant, although somewhat attenuated at 37 C, was still found to cause damage to the ciliated epithelium and to replicate at both temperatures. THIS BEHAVIOR IS SIMILAR TO THAT AFTER INOCULATION OF TS-1 INTO VOLUNTEERS. This in vitro model may prove useful in the study of RSV disease and in the evaluation of candidate live virus vaccines.

Animals↗
PubMed1978

Temperature-sensitive mutants of influenza A virus: production and characterization of A/Victoria/3/75-ts-1[E] recombinants.

The Hong Kong/68-ts-1[E] virus, which has a 38 degrees C shutoff temperature for plaque formation, has been proposed as a donor of its two ts lesions to new variants of influenza A virus that pose an epidemic threat. To further examine whether the acquisition of the two ts-1[E] lesions will predictably attenuate new influenza A variants, the HK/68-ts-1[E] virus was mated with the A/Vic/3/75 wild-type virus. The Vic/75-ts-[E] recombinants that had the two ts-1[E] lesions also had a 38 degrees C shutoff temperature. Two Vic/75-ts-1[E] recombinants (clones 81 and 113) that had the two ts-1[E] lesions, a 38 degrees C shutoff temperature, and the Vic/75 hemagglutinin and neuraminidase glycoproteins were similar to each other and to their ts-1[E] parent in the pattern of replication and genetic stability in hamsters. These findings support the hypothesis that the acquisition of the two ts-1[E] lesions will predictably attenuate wild-type influenza A virus. Each Vic/75-ts-1[E] recombinant virus that possessed only the group 1 ts-1[E] lesion had a 39 degrees C shutoff temperature. Two of three of the Vic/75-ts-1[E] recombinants that had only the group 2 ts-1[E] lesion had a 39 degrees C shutoff temperature. This suggests that the HK/68-ts-1[E] donor virus contains two ts genes each of which by itself restricts plaque formation at 39 degrees C and above. The HK/68-ts-1[E] parent virus and its Vic/75 recombinant clones 81 and 113 were evaluated in ferret tracheal organ cultures maintained at permissive and restrictive temperatures. The Vic/75-ts-1[E] clone 81 differed from its parent and sister clone 113 in that it replicated readily and caused ciliostasis at 37 degrees C, a temperature restrictive for the replication of other ts-1[E] recombinants with a 38 degrees C shutoff temperature. The genetic basis underlying this difference was not elucidated.

Antigens, Viral↗
PubMed1977

Temperature-sensitive mutants of influenza virus. XIII. Evaluation of influenza A/Hong Kong/68 and A/Udorn/72 ts and wild-type viruses in tracheal organ culture at permissive and restrictive temperatures.

For development of an in vitro assay of attenuation for virus vaccine candidates, tracheal ring organ cultures from young ferrets were infected with influenza A/Hong Kong/68 and A/Udorn/72 temperature-sensitive (ts) recombinant and wild-type viruses and observed for 21 days at permissive (33 C) and restrictive (37 C) temperatures for effects on ciliated epithelium and viral replication. Results were compared with the known effects of these viruses in humans. Viruses that damaged ferret cilia and grew to high titers at 37 C were insufficiently attenuated for humans, and viruses that failed to damage cilia and grew to low titers at 33 C were excessively attenuated for humans. This system did not completely differentiate the relative virulence of A/Hong Kong/68 ts recombinants for humans but was successful for the A/Udorn/72 ts recombinants. This organ culture system has adjunctive usefulness for detection of most insufficiently attenuated influenza A vaccine candidates and for identification of excessively attenuated candidates that might contain non-ts lesions.

Animals↗
PubMed1977

Studies of inactivated influenza virus vaccines in hospital employees: reactogenicity and absenteeism.

The impact of a mass influenza vaccination program on the operation of a major medical center was evaluated in adult volunteer employees who were given either ether-split or whole-virus bivalent influenza vaccine in a double-blind manner by jet-injector gun. Each volunteer completed a reaction information form, nurses monitored temperatures, and data on absenteeism of the employees of the Nursing Service and the Building Management Service were collected. The results of this study demonstrated that the mass campaign did not adversely affect absenteeism. However, the whole-virus vaccine caused significantly more local, systemic, and febrile reactions thant the split-virus vaccine. Purified inactivated influenza virus vaccines can be given in a mass campaign to hospital personnel without adversely affecting the operation of the hospital.

Absenteeism↗
PubMed1976

Epidemiology of influenza in the elderly: evidence of virus recycling.

During the Hong Kong influenza epidemic of 1968-1969 the attack rate among persons born prior to 1890 was about one-third the rate among persons born after 1899. During an Asian influenza epidemic in the same community two years earlier there was no apparent age effect. Most persons born before 1890 had detectable pre-epidemic antibody against A/Hong Kong/68 whereas most persons born after 1899 had no detectable pre-epidemic antibody. The lower attack rate in the older age group is consistent with the hypothesis that influenza A viruses with similar or identical hemagglutinins can reemerge over time and that remote previous experience with the same or a similar strain can be protective. Also, no age group born after 1890 was found to have a high prevalence of antibody against A/England/72 or A/Dunedin/73, the successors to A/Hong Kong/68, indicating that recycling of hemagglutinin antigens is not strictly ordered.

Age Factors↗
PubMed1975

Application of the single radial diffusion test for assay of antibody to influenza type A viruses.

Single radial diffusion (SRD) tests for antibodies to influenza type A hemagglutinin, neuraminidase, nucleoprotein, and matrix protein antigens were compared with conventional hemagglutination inhibition, neuraminidase inhibition, and complement fixation tests. Sera used in this study were obtained in 1968-1969 from volunteers before and after vaccination and before and after an ensuing epidemic of Hong Kong influenza. The SRD test compared favorably with conventional tests for assessment of vaccine- or infection-induced rises in antibody titers to influenza type A viruses. Little linear relationshiip was seen between zone areas with SRD and titers with conventional tests, suggesting that the SRD test may detect antibody of different quality or specificity. The SRD seemed equal to the hemagglutination inhibition test for predicting susceptibility to influenza. SRD is a simple test for the recognition of antibody to various antigenic components of the influenza virus and could prove to be a valuable epidemiological tool.

Antibodies, Viral↗
PubMed1975

An 'in vitro' marker of attenuation for live influenza virus vaccine candidates.

Organ cultures of ferret tracheal rings maintained in tubes for up to two months supported the growth of several strains of influenza A viruses produced by genetic recombination. These strains were developed as possible candidates for live attenuated influenza virus vaccines. By observing the effects on cilia and titrating the growth in eggs it was possible to rank these various influenza strains in order of descending virulence for the respiratory epithelium in organ culture. This rank corresponded in general to the virulence of these viruses for human volunteers. Viruses too virulent to use as vaccine strains in man regularly destroyed the ciliated epithelium of ferret trachea while strains attenuated for man usually did not. Although the ciliated respiratory epithelium of ferret was not as sensitive as that derived from human embryonic trachea, this test did identify all the tested strains too virulent for evaluation in human volunteers.

Animals↗