Biomedical subjects

S F Little

Publications and source records attributed to S F Little.

24 records · Page 2Linked to original sources

PubMed1990

Identification of Bacillus anthracis by using monoclonal antibody to cell wall galactose-N-acetylglucosamine polysaccharide.

Guanidine extracts of crude Bacillus anthracis cell wall were used to vaccinate BALB/c mice and to develop monoclonal antibody (MAb) to vegetative cell surface antigens. Two hybridomas selected during this study produced immunoglobulin M immunoglobulins, which appear to be directed to an epitope associated with the galactose-N-acetyl-D-glucosamine polysaccharide. Both demonstrated specificity in their binding to purified B. anthracis cell wall, o-stearoyl-polysaccharide conjugates, and intact, nonencapsulated vegetative cells. The interaction of the MAbs with purified polysaccharide was inhibited by 0.5 M galactose and lactose but not by N-acetylglucosamine, glutamate, glycine, or glycerol. Inhibition by glucose or sucrose was approximately 75% of that seen with galactose. Electron microscopy showed that both MAbs interacted with the cell wall of vegetative cells as well as with the cortex of spores. Neither MAb reacted with encapsulated vegetative cells, such as those from infected guinea pigs, nor did they react with intact spores. After conjugation to fluorescein isothiocyanate, the MAbs stained intensely all B. anthracis strains tested, whereas with two exceptions, none of the strains of 20 other Bacillus spp. was stained. The exceptions, strains of Bacillus cereus, could be differentiated from B. anthracis by being beta-hemolytic on blood agar.

Acetylgalactosamine↗

PubMed1988

Separation of three exotoxic factors of Bacillus anthracis by sequential immunosorbent chromatography.

Protective antigen and lethal factor components were isolated directly from crude culture supernatant of Bacillus anthracis by sequential immunosorbent chromatography using immobilized monoclonal antibodies (MAB) against the respective toxins. The immunological activity of protective antigen, lethal factor and edema factor were purified by 1.2-, 6.3- and 2.3-fold, respectively, with recoveries of 63, 70 and 46%, respectively. All three components retained biological activity when combined to form lethal toxin or edema toxin, PA + LF and PA + EF, respectively, after the purification process, and were not contaminated with any of the other components. The order of immunosorbent columns during the purification process was found to be important. The best results were obtained when the protective antigen was removed initially from the crude culture supernatant.

Animals↗

PubMed1988

Production and characterization of monoclonal antibodies to the protective antigen component of Bacillus anthracis toxin.

Thirty-six monoclonal antibodies to the protective antigen protein of Bacillus anthracis exotoxin have been characterized for affinity, antibody subtype, competitive binding to antigenic regions, and ability to neutralize lethal and edema toxin activities. At least 23 antigenic regions were detected on protective antigen by a blocking, enzyme-linked immunosorbent assay. Two clones, 3B6 and 14B7, competed for a single antigenic region and neutralized the activity of both the lethal toxin in vivo (Fisher 344 rat) and the edema toxin in vitro (CHO cells). These two antibodies blocked the binding of 125I-labeled protective antigen to FRL-103 cells. Our results support the proposal that binding of protective antigen to cell receptors is required for expression of toxicity.

Animals↗

PubMed1986

Comparative efficacy of Bacillus anthracis live spore vaccine and protective antigen vaccine against anthrax in the guinea pig.

Several strains of Bacillus anthracis have been reported previously to cause fatal infection in immunized guinea pigs. In this study, guinea pigs were immunized with either a protective antigen vaccine or a live Sterne strain spore vaccine, then challenged with virulent B. anthracis strains isolated from various host species from the United States and foreign sources. Confirmation of previously reported studies (which used only protective antigen vaccines) was made with the identification of 9 of the 27 challenge isolates as being vaccine resistant. However, guinea pigs immunized with the live Sterne strain spore vaccine were fully protected against these nine isolates. In experiments designed to determine the basis of vaccine resistance, guinea pigs which were immunized with individual toxin components and which demonstrated enzyme-linked immunosorbent assay antibody titers comparable to those induced by Sterne strain vaccine were not protected when challenged with a vaccine-resistant isolate. We concluded that antibodies to toxin components may not be sufficient to provide protection against all strains of B. anthracis and that other antigens may play a role in active immunity. As a practical matter, it follows that the efficacy of anthrax vaccines must be tested by using vaccine-resistant isolates if protection against all possible challenge strains is to be assured.

Animals↗

PubMed1980

Treatment of tularemia, including pulmonary tularemia, with gentamicin.

An alternative to streptomycin for treatment of possible tularemia would be useful on occasions when a patient develops a perplexing pneumonia that does not respond to initial treatment. In geographic areas where tularemia is endemic, an antimicrobial drug that is bactericidal for Francisella tularensis and is also effective against a spectrum of common pulmonary pathogens, including the Enterobacteriaceae and most strains of Pseudomonas aeruginosa, would be desirable. The purposes of this report are (1) to describe observations regarding the in vitro susceptibility of Francisella tularensis to streptomycin, kanamycin, and gentamicin; (2) to describe in vivo efficacy of these drugs in mouse tularemia; (3) to describe the results in 10 patients with tularemia treated with gentamicin. Gentamicin was bactericidal for Francisella tularensis in vitro, was effective in mouse tularemia when given in large doses, and was effective in humans when given in the standard recommended dose.

Aged↗

PubMed1979

Immunologic protection against the Legionnaires' disease bacterium in the AKR/J mouse.

Female AKR/J mice were challenged with the Washington strain of Legionnaires' disease (LD) bacteria. Nonimmunized mice inoculate intraperitoneally with 2 x 10(8) colony forming units became ill within 4 h and died within 24 h. Progressive histopathologic changes initiated as early as 2 h after inoculation involved the lymphoid organs, the crypts of the small intestine, and the liver. Necrosis with minimal inflammatory cell reaction was the primary lesion. Immunization with a soluble LD bacterial antigen failed to prevent illness but protected against death and development of abnormal histologic changes.

Animals↗