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Biomedical subjects

E W Larson

Publications and source records attributed to E W Larson.

34 records · Page 2Linked to original sources
PubMed1981

In vitro responses of guinea pig peritoneal macrophages to Legionella pneumophila.

Transmission and scanning electron microscopy were used to study the phagocytosis of virulent and avirulent strains of Legionella pneumophila. The interaction between L. pneumophila and peritoneal macrophages from normal guinea pigs or from animals that had survived infection was studied. The virulent strains survived and proliferated within the phagocyte after ingestion by either type of macrophage, whereas the avirulent strain of bacteria was killed by normal macrophages. Although the addition of immune serum enhanced phagocytosis, the outcome was the same as with normal serum.

Animals↗
PubMed1981

Evaluation of a killed phase I Coxiella burnetii vaccine in cynomolgus monkeys (Macaca fascicularis).

The protective efficacy of a killed, purified, phase I Coxiella burnetii vaccine was tested in cynomolgus monkeys. Monkeys vaccinated once with 30 micrograms of the antigen were challenged 6 or 12 months later with virulent phase I rickettsiae administered in small-particle aerosols. The vaccine provided only partial protection, since some of the challenged monkeys developed clinical signs of illness. However, the vaccinated animals did not develop pneumonia as determined by radiographic evaluation nor any hematologic or chemical changes except for an increase in fibrinogen. Although rickettsiae were isolated from peripheral blood in vaccinated monkeys, the rickettsemia persisted for only 1-2 days; whereas, organisms were recovered from unvaccinated animals for 6-7 days. All vaccinated animals had circulating microagglutinating antibodies to phase I and phase II antigens 6 and 12 months after vaccination.

Animals↗
PubMed1980

Aerosol stability and respiratory infectivity of japanese B encephalitis virus.

Experiments were conducted to examine the aerosol stability and respiratory infectivity of Japanese B encephalitis virus. At 75 degrees F (about 24 degrees C), survival of the virus as aerosol was inversely related to relative humidity. After correction for physical decay, the mean virus half-lives of the virus were 28, 38, and 62 min at relative humiditis of 80, 55, and 30%, respectively. Virus recoveries as aerosol at 4 min aftr dissemination generally exceeded the theoretical limit of 100%, based on the amount disseminated, to suggest that the process of dissemination operated to deagglomerate or release bound virus from the tissue cells in suspension. Swiss-ICR mice and golden Syrian hamsters were highly susceptible to lethal infections after respiratory challenge. Hartley strain guinea pigs and Fisher-Dunning rats, although infected, based on seroconversion observations, survived the infections. Deaths occurred in squirrel monkeys only after exposure to a high aerosol dose of virus (10(6.0) plaque-forming units). Studies of the virus concentration dynamics and histopathological findings in mouse tissues after aerosol challenge supported a hypothesis for direct transport of virus across the foramina of the cribriform plate to the tissues of the central nervous system to produce primary encephalitis.

Aerosols↗
PubMed1979

Cynomolgus monkey model for experimental Q fever infection.

A subhuman primate model was developed for study of the pathogenesis of infection with Coxiella burnetii. Cynomolgus monkeys (Macaca fascicularis) that were exposed to 10(5) mouse median infectious intraperitoneal doses of C. burnetii in a small-particle aerosol developed clinical signs of illness and pathologic changes characteristic of Q fever infection in humans. All monkeys had radiologic evidence of pneumonia by day 9. Antibodies to C. burnetii were detectable by the indirect fluorescent antibody test by day 7. These data indicate that the cynomolgus monkey is a suitable model for study of the pathogenesis of Q fever infection and may prove valuable in the evaluation of C. burnetii vaccines.

Aerosols↗
PubMed1978

Cell-mediated immune responses of guinea pigs to an inactivated phase I Coxiella burnetii vaccine.

The ability of a killed phase I Coxiella burnetii vaccine to induce cell-mediated immune responses in guinea pigs was studied. Cell-mediated immune responses were assessed by the inhibition of macrophage migration and lymphocyte transformation assays. The macrophage migration response occurred rapidly and was detected at high levels, but was relatively short-lived. In contrast, the lymphocyte transformation response developed more slowly, and persisted for a longer period. The vaccine, given in a single dose or in two doses 1 week apart, protected guinea pigs from a subsequent virulent challenge.

Animals↗
PubMed1978

Experimental Q fever infection in congenitally athymic nude mice.

Congenitally athymic nude (nu/nu) mice and their phenotypically normal (nu/+) euthymic littermates were exposed to Coxiella burnetii administered as small-particle aerosols. After challenge, both strains of mice became infected, as characterized by rickettsemia, viable rickettsiae in the spleen, and serological conversion. The major difference noted was that euthymic animals had cleared rickettsiae from peripheral circulation and the spleen within 14 days. In contrast, rickettsiae were detected and isolated from spleen and blood of athymic mice through 60 days.

Animals↗
PubMed1977

Continuous aerosol therapy system using a modified Collison nebulizer.

A Collison nebulizer was incorporated into an exposure system for administering antiviral compounds as continuous aerosols to mice infected with influenza virus. The nebulizer was modified to control aerosol output by varying the liquid feed rate. A multiple regression equation was developed from data obtained with uranine dye to define the aerosol concentration of the dye in the system as a function of the concentration of the dye in the spray fluid and the rate at which it was aerosolized. The rate of change of the concentration of the test solution due to evaporative losses was also ascertained for a 1-ml/min feed rate over a 23.5-h period of operation. Procedures are outlined for using these relationships to determine the concentration of a given drug that will result in a given dose. Performance data for the drug ribavirin are presented.

Aerosols↗
PubMed1976

Influenza virus population dynamics in the respiratory tract of experimentally infected mice.

Virus population dynamics in the lungs, trachea, and nasopharynx of Swiss-ICR mice were studied after respiratory challenge with mouse-adapted preparations of strain A2/Aichi/2/68 influenza virus. Markedly higher doses of virus were required to produce infection with nasopharyngeal challenge than with bronchoalveolar challenge. In all of the infections, the highest virus concentrations were observed in the lungs. Peak concentrations in the trachea were lower than in the lungs but higher than in the nasopharynx. Decreasing virus levels were observed by 120 h after challenge and were generally below detectable levels by the end of 10 days. A compartmental model of a single mathematical form was developed which provided close fits of the virus concentration measurements regardless of the challenge dose, site of initial deposition, or respiratory tissue considered. The model includes seven compartments with five associated rate parameters. The application of compartmental modeling techniques and expression of the virus population dynamics in mathematical terms is regarded as a new approach to the study of the pathogenesis of infections.

Administration, Intranasal↗
PubMed1974

Modified spinning top homogeneous spray apparatus for use in experimental respiratory disease studies.

The May spinning top generator was adapted to a modified Henderson tube for producing large aerosol particles (>4 mum) to obtain almost exclusive upper respiratory tract deposition of infectious aerosols in exposed mice. The system was installed in a biological safety cabinet to permit experimentation with pathogens. A novel mechanism utilizing parts from a machinists micrometer and the mechanical stage from a light microscope was developed for the spinning top generator as a means for precisely positioning the liquid feed needle. Aerosol light-scatter properties were continuously analyzed to provide relative measures of particle size distribution and aerosol concentration. When mice were exposed to influenza virus aerosols in which none of the virus was contained in particles with aerodynamic diameters <4 mum, essentially all of the virus was deposited in the upper respiratory tract tissues.

Aerosols↗
PubMedDate not supplied

Three-dimensional reconstruction of tubular myelin.

The lipid and protein components of pulmonary surfactant are synthesized by alveolar type II cells and stored in their secretory granules, the lamellar bodies. Tubular myelin is a highly ordered surfactant structure that is lung specific and produced in the alveolar airspace. Recent work identified Ca2+, surfactant apoproteins A and B, and saturated phospholipids as necessary for tubular myelin structure and function. We have used serial ultrathin sections from fetal rat lungs and reconstructed the three-dimensional structure of tubular myelin. The spheres of tubular myelin we viewed were 2-3 microns in diameter and were surrounded by up to 20 lamellar bodies, each apparently simultaneously contributing material to the tubules. We measured a long-range symmetry of the tubules, which were folded about a central axis and showed a repeated crossing of individual tubes from one side to the other of the large structure. The tubes appeared closed on their outer edges and there was a delay in the penetration of tubules by cationic ferritin added to tissue slices containing the tubular myelin, although within a few minutes tracer appeared in the lumina and on the walls of the tubules. The three-dimensional images were compatible with existing views of tubular myelin.

Animals↗