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Biomedical subjects

G O Nelson

Publications and source records attributed to G O Nelson.

At least 19 recordsLinked to original sources

Immunization against anthrax with Bacillus anthracis protective antigen combined with adjuvants.

The protective efficacy of immunization against anthrax with Bacillus anthracis protective antigen (PA) combined with different adjuvants was tested in Hartley guinea pigs and CBA/J and A/J mice. Adjuvant components derived from microbial products that were tested included threonyl-muramyl dipeptide (threonyl-MDP); monophosphoryl lipid A (MPL); trehalose dimycolate (TDM); and the delipidated, deproteinized, cell wall skeleton (CWS) from either Mycobacterium phlei or the BCG strain of Mycobacterium bovis. Non-microbially derived adjuvants tested included aluminum hydroxide and the lipid amine CP-20,961. In guinea pigs, all adjuvants and adjuvant mixtures enhanced antibody titers to PA as well as survival after a parenteral challenge of virulent B. anthracis Ames spores. In contrast, PA alone or combined with either aluminum hydroxide or CP-20,961 failed to protect mice. Vaccines containing PA combined with threonyl-MDP or MPL-TDM-CWS protected a majority of female CBA/J mice. Statistical analysis of survival data in the guinea pigs indicated that PA-MPL-CWS and PA-MPL-TDM-CWS were more efficacious than the currently licensed human anthrax vaccine.

Adjuvants, Immunologic

Cell-mediated and humoral immune responses induced by scarification vaccination of human volunteers with a new lot of the live vaccine strain of Francisella tularensis.

Tularemia is a disease caused by the facultative intracellular bacterium Francisella tularensis. We evaluated a new lot of live F. tularensis vaccine for its immunogenicity in human volunteers. Scarification vaccination induced humoral and cell-mediated immune responses. Indications of a positive immune response after vaccination included an increase in specific antibody levels, which were measured by enzyme-linked immunosorbent and immunoblot assays, and the ability of peripheral blood lymphocytes to respond to whole F. tularensis bacteria as recall antigens. Vaccination caused a significant rise (P less than 0.05) in immunoglobulin A (IgA), IgG, and IgM titers. Lymphocyte stimulation indices were significantly increased (P less than 0.01) in vaccinees 14 days after vaccination. These data verify that this new lot of live F. tularensis vaccine is immunogenic.

Antibody Formation

A longitudinal study of Junin virus activity in the rodent reservoir of Argentine hemorrhagic fever.

We monitored Junin virus (JV) activity in rodent populations for 30 months at seven mark-recapture grids located in agricultural fields and adjacent roadsides and fence lines in endemic and nonendemic areas of Argentine hemorrhagic fever. Blood and oral swabs taken from rodents captured at five-week intervals were analyzed by enzyme-linked immunosorbent assay for JV antigen (Ag). Calomys laucha and C. musculinus were the most frequently captured rodents, making up 47% and 22% of captures, respectively. Of 41 Ag-positive captures, 37 were C. musculinus and four were C. laucha; 34 were from two trapping grids in the same locality. Antigen-positive Calomys were more frequently male (76%), and were found significantly more frequently among the oldest animals and the largest body mass classes. These patterns, combined with the greater mobility and higher frequencies of wounds among males than females, implicated horizontal transmission as the primary route of JV transmission between rodents. Seasonal maximum levels in JV prevalence (up to 25% of captured Ag-positive C. musculinus) occurred during periods of maximal population densities of Calomys. Spatial distribution of Ag-positive rodents reflected habitat preferences; most Ag-positive C. musculinus were captured from border habitats (roadsides and fence lines), and all Ag-positive C. laucha were captured in crop fields. These distinct, but previously undocumented, habitat preferences suggest that the disease in humans may be related to exposures to the primary reservoir species, C. musculinus, in border habitats rather than in crop fields.

Age Factors

Egg hatching of Aedes mosquitoes during successive floodings in a Rift Valley fever endemic area in Kenya.

Floodwater Aedes breeding habitats in central Kenya were sequentially flooded to determine the numbers of mosquito eggs hatching during each flooding. Approximately 90% of the larvae sampled during 4 floodings emerged during the initial flooding. The number of Aedes eggs hatching during the second flooding was lowest of all 4 floodings, and no significant differences in the amount of egg hatching during floodings 3 and 4 were seen. Unhatched Aedes eggs were present in soil samples collected after the final flooding. The possible implications of these findings with regard to Rift Valley fever virus control are discussed.

Aedes

Resistance to the Sterne strain of B. anthracis: phagocytic cell responses of resistant and susceptible mice.

Inflammatory responses were compared in vivo, and host phagocytic cell functions compared in vitro, of mice resistant (CBA/J) and susceptible (A/J) to lethal infection with the Sterne strain of Bacillus anthracis. Polymorphonuclear leukocyte (PMN) and macrophage responses at the initial site of infection were slower in A/J mice than in CBA/J mice. Whereas in A/J mice, the number of PMN ultimately responding to infection was equal to, or greater than, that in CBA/J mice, fewer macrophages accumulated. A/J mice failed to clear relatively low doses of the organisms and died. In vitro, chemotactic responses to both serum- and bacteria-derived attractants were similar for macrophages from A/J and CBA/J mice but were reduced for PMN from A/J mice. PMN and macrophages from the two mouse strains phagocytosed and killed spores in vitro to a similar extent, although killing by A/J PMN could be blocked by prior uptake of large numbers of killed spores. Thus susceptibility to lethal infection with Sterne strain correlated with the delayed influx (PMN) and reduced accumulation (macrophages) of phagocytes at the initial site of infection, but not with defective in vitro uptake or killing of spores.

Animals

Influence of body weight on response of Fischer 344 rats to anthrax lethal toxin.

Groups of Fischer 344 rats were injected intravenously with Bacillus anthracis culture supernatant containing crude anthrax toxin. Times to death of rats given identical toxin preparations varied directly with the weights of the rats (P = 0.0001). In contrast to previous reports, the data indicate that rat weight must be taken into account during in vivo assays of anthrax lethal toxin activity.

Animals

Efficacy of a commercial bacterin in protecting strain 13 guineapigs against Bordetella bronchiseptica pneumonia.

Bordetella bronchiseptica is known to be endemic in many guineapig (Cavia porcellus) colonies, and periodically is the aetiological agent of fatal epizootics of bronchopneumonia. A commercial, non-adjuvant B. bronchiseptica bacterin, which is approved for use in canines, was evaluated for induction of a protective immune response in Strain 13/N guineapigs against an airborne challenge of virulent B. bronchispeptica in small-particle aerosol. Seronegative animals were vaccinated on days 0 and 21 with intramuscular injections of 0.2 ml of bacterin. Humoral antibody titres of the vaccinated animals, as determined by ELISA, ranged from 128-1024 on day 49. On day 30 following the second dose of bacterin (study day 51), 12 vaccinated and 12 PBS sham-vaccinated animals were exposed to an inhaled dose of 4.3 x 10(5) CFU of B. bronchiseptica (325 LD50). Vaccinated, challenged animals remained clinically normal, although each guineapig did develop a localized upper respiratory infection. The rate of weight gain as well as rectal temperature of these animals were analogous to those exhibited by the control groups. Examination of 4 of the vaccinated, challenged animals on day 7 after exposure showed bacteria present in moderate to high numbers in the larynx and trachea but only minimally detectable in the lungs; by 30 days after exposure, the numbers of bacteria in the larynx and trachea were diminished, with none being detected in the lungs. Pathological alterations induced by B. bronchiseptica were not detected at either day 7 or day 30 after challenge in any of the vaccinated, challenged animals. Protection induced in Strain 13/N guineapigs by the commercial canine bacterin was sufficient to preclude the development of pulmonary disease, even in animals presented with a massive challenge of virulent bacteria in a small-particle aerosol.

Animals

Enhancement of air filtration using electric fields.

Although polarized electrostatic air filters are efficient air filtrating devices, their main disadvantages are difficulty in collecting conductive particles or in operating at relative humidities above 70%. We describe here a new filter design that eliminates these problems. A nonconductive media, normally a glass fiber mat, is placed between two insulated conductive screens. As the voltage across the screens is increased, the penetration of particles decreases exponentially. Increasing the electric field from 0 to 10 kV/cm will decrease the mass penetration from 60% to less than 10% of a polydispersed 0.8 micrometer ammd(sigma g = 2.0) sodium chloride aerosol. The experimental effects of face velocity, particle charge and size, packing density, fiber size, and screen insulation mirror the theoretical effects of these variables on particle penetration.

Air Conditioning

Respirator cartridge efficiency studies: VI. Effect of concentration.

The service life of organic vapor cartridges was determined for ten vapors at concentrations between 50 and 3000 ppm. The breakthrough time (tb) conformed to the empirical expression tb = aCf, where C is the concentration in ppm and a and be are constants. The average value for b at 10% breakthrough was -0.67 +/- 0.17. The service life is inversely proportional to flow rate for acetone and benzene.

Adsorption

Respirator cartridge efficiency studies: VII. Effect of relative humidity and temperature.

Cartridge service life is not appreciably affected at relative humidities below 50%. However, performance is severely compromised when the humidity exceeds 65%. Experimental values are compared from those calculated from the adsorption isotherm, Mecklenburg and modified Wheeler equations. Calculations indicate that temperature does not play a significant role in service life predictions.

Adsorption

Respiratory cartridge efficiency studies: VIII. summary and conclusions.

The theory of solvent vapor adsorption of activated carbon is reviewed. Calculated and experimental cartridge service life values are compared using various breathing rates, relative humidities, concentrations and solvent vapors. Cartridge service life (the 10% breakthrough time) can be estimated from the emperical expression: t 10% = 2.4 X 10(6) WC (A + BT)/C 2/3 MQ Carbon weight (wc), relative solvent volatility (a, b and t) concentration (C), molecular weight (M) and breathing rate (Q) all play a vital role in cartridge performance predictions.

Adsorption

Preparation of mixtures of humidified air with CO, SO2, NO2, NH3, NH2CH3, Cl2, and HCl to measure respirator cartridge and canister service life.

Four systems have been fabricated to measure the effective service life of respirator cartridges and canisters. The four systems employ carbon monoxide, sulfur dioxide/nitrogen dioxide, ammonia/methylamine, and chlorine/hydrogen chloride as contaminants. Each system produces test concentrations in the low percentage range (typically 0.05 to 3.0%) at flow rates of 32 and 64 liters/min and at relative humidities between 20 and 95%. Suitable anlyzers have been provided to measure the downstream concentration from 1 to 500 ppm as a function of time. Holders have been designed to accommodate the wide size variation of commercially available cartridges and canisters.

Air