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Biomedical subjects

K C Milner

Publications and source records attributed to K C Milner.

At least 19 recordsLinked to original sources
PubMed1982

Induction of resistance to tuberculosis in mice with defined components of Mycobacteria and with some unrelated materials.

Factors contributing to protection against experimental tuberculosis have been studied with refined and well-characterized fractions from mycobacteria and with certain unrelated antigens. Mice were vaccinated intravenously with various combinations of materials presented on minute oil droplets in saline emulsion and were later challenged by aerosol. The minimal composition of an effective vaccine was P3 (a trehalose mycolate similar to cord factor) plus an antigen, which could be tuberculo-protein, or a low-molecular-weight tuberculin-active peptide, or unrelated antigen such as bovine serum albumin or bacterial endotoxin. Development of a hypersensitivity granuloma in the lungs appeared to be essential to protection in this laboratory model.

Animals↗
PubMed1982

Induction of resistance to tuberculosis in mice with defined components of mycobacteria and with some unrelated materials.

Factors contributing to protection against experimental tuberculosis have been studied with refined and well characterized fractions from mycobacteria and with certain unrelated antigens. Mice were vaccinated intravenously with various combinations of materials presented on minute oil droplets in saline emulsions and were later challenged by aerosol. The minimal composition of an effective vaccine was P3 (a trehalose mycolate similar to cord factor) plus an antigen, which could be tuberculoprotein, or a low-molecular-weight tuberculin-active peptide, or unrelated antigen such as bovine serum albumin or bacterial endotoxin. Development of a hypersensitivity granuloma in the lungs appeared to be essential to protection in this laboratory model.

Animals↗
PubMed1977

Lethality for mice and chick embryos, pyrogenicity in rabbits and ability to gelate lysate from amoebocytes of Limulus polyphemus by lipopolysaccharides from Bacteroides, Fusobacterium and Veillonella.

Phenol-water extracted lipopolysaccharides (LPS) from Veillonella, Fusobacterium nucleatum, Bacteroides fragilis and Bacteroides melaninogenicus were lethal for mice and 11-days-old chick embryos, pyrogenic in rabbits, and gelated Limulus amoebocyte lysate. Mouse lethality was considerably enhanced by actinomycin-D. In all test systems the endotoxin activity of Veillonella and Fusocbacterium LPS was comparable to that of LPS from Salmonella enteritidis, which was included as a reference endotoxin. The endotoxicity of the Bacteroides LPS was very low. While nanograms of the Veillonella and Fusobacterium LPS killed the chick embryos and gelated the Limulus lysates, microgram amounts of the Bacteroides LPS were needed to give positive reaction in the same test systems. As much as 74 microgram of the most active B. fragilis LPS were required to give a typical biphasic fever response in rabbits. A significant correlation was found between all test results (r = 0.90-0.98, p less than 0.001).

Animals↗
PubMed1977

New test for endotoxin potency based upon histamine sensitization in mice.

The results of a test of endotoxic potency based upon the development of histamine hypersensitivity in mice were compared with the results obtained by testing the same materials for pyrogenicity in rabbits and lethality for chicken embryos (CELD50). The results of the histamine hypersensitization test (HHT) correlated well with those of the other two tests. The sensitivity of the HHT was about the same as that of the CELD50 assay. The HHT may provide a relatively inexpensive, fast, and reliable assay method for endotoxin laboratories that do not have the facilities for the more elaborate assays.

Animals↗
PubMed1976

Immunotherapy with nonviable microbial components.

Structural components of microorganisms have been studied for immunopotentiating effect with the aid of transplantable (line 10) tumors in syngeneic guinea pigs. Microbial components were associated with oil droplets, suspended in Tween-saline, and injected intralesionally. BCG cell walls, given in this way, produced regression and cure of 50-60% of established tumors, as did viable BCG. Lipid extraction markedly reduced the tumor-regressing potency of cell walls, but P3, a trehalose mycolate present in the extract, restored full activity to the cell wall residue. P3 alone was nonsensitizing and had no antitumor activity, but it enhanced the latter property of various other microbial products. For example, the cure rates produced by cell walls of M. tuberculosis, M. bovis, M. phlei, or M. smegmatis were enhanced from 20-60% to as much as 90% by addition of P3. P3 also conferred antitumor activity on products from unrelated microbes, such as cell walls of E. coli, and in combination with endotoxins from rough Re mutant salmonellae, it produced cure rates of up to 93%. These results suggest that P3 is essential to the immunopotentiating activity of mycobacteria and that it may be broadly applicable in immunotherapy of cancer with microbial agents.

Animals↗
PubMed1976

Preparation and properties of a national reference endotoxin.

A large pool of refined endotoxin was prepared from Escherichia coli O113 by extraction with hot acqueous phenol. It was characterized chemically and biologically and will be available for a reference standard designated as reference endotoxin EC.

Animals↗
PubMed1975

Tumor regression caused by endotoxins and mycobacterial fractions.

A transplantable hepatocarcinoma of guinea pigs was used as an experimental model for immunotherapy of cancer. Earlier work showed that complete regression of 6- to 7-day-old tumors could be obtained in about 60% of cases by inoculation of the tumors with live BCG or certain fractions of BCG attached to minute oil droplets and suspended in Tween-saline. One of the most essential fractions was P3, a nonsensitizing, nonantigenic trehalose mycolate related to, but not identical with, cord factor. We now report that oil-droplet preparations containing P3 and bacterial endotoxin (ET) produced cure rates of up to 90% in the same system. In addition, regression was faster than with BCG, and older tumors could be treated successfully. The most effective ET's were from rough strains of salmonellae, known as Re mutants, which could not synthesize and attach the polysaccharide portion of endotoxin.

Animals↗
PubMed1972

Biological and chemical characterization of toxic substances from Candida albicans.

Whole cells, morphological components, and various extracts of Candida albicans were tested for toxicity by methods involving biological activities ordinarily used to characterize bacterial endotoxin. Fungal preparations exerted several of these activities, but only at much higher dose levels than those required for bacterial products. Both fungal cell walls and intact cells were pyrogenic in rabbits and lethal to actinomycin D-treated mice, but only the former were also lethal to chicken embryos; neither coagulated a hemolysate of horseshoe crabs. Wallfree fungal protoplasm was minimally pyrogenic but negative in the other assays. Bacterial endotoxin was strongly active in all four systems. The toxicity of fungous cell walls was undiminished after exposure to strong alkali, a treatment which destroyed bacterial endotoxin. Extracts obtained with hot phenol-water or potassium hydroxide killed mice but were nonpyrogenic. A defatted and enzyme-digested ethylenediamine extract was both lethal and pyrogenic. Particulate fungal materials but not bacterial endotoxin induced a granulomatous response in prepared mice. These data indicate that contaminating bacterial endotoxin was not responsible for the biological effects of fungal products and suggest that C. albicans may contain at least two different toxic components. Chemical analyses were performed on soluble fractions, but a role in toxicity could not be assigned to any identified component.

Animals↗
PubMed1969

Alteration of physical, chemical, and biological properties of endotoxin by treatment with mild alkali.

Treatment with alkali is one of several methods for removing fatty acids from bacterial endotoxins and, in the process, detoxifying the material. Saponification of fatty acid esters is the major detectable chemical change produced by alkali; however, kinetic studies of mild alkaline hydrolysis of endotoxin failed to correlate rates of detoxification with rates of loss of ketodeoxyoctonates, heptose, O-acetyl groups, or fatty acid esters. The alterations occurring during the critical stages of hydrolysis apparently changed the essential chemical conformation of endotoxic particles before cleavage of a significant amount of material took place. The rates of both saponification and detoxification were markedly increased by carrying out the reaction in media of ethyl alcohol or dimethylsulfoxide instead of water.

Alkalies↗
PubMed1969

Occult endotoxin in bacterial protoplasm.

Protoplasm separated from disrupted cells of gram-negative bacteria was extracted with hot phenol-water or was precipitated with ethyl alcohol after digestion with Pronase. These methods recovered about 10 times more endotoxin than was detectable in the untreated protoplasm. Inactivation of endotoxin by protoplasm also occurred in vitro when the endotoxin was first dissociated into subunits before reaction with protoplasm. Despite this increased yield from another source, the major proportion of endotoxin was still found in the cell walls.

Animals↗
PubMed1968

Modification of selected host-reactive properties of endotoxin by treatment with sodium deoxycholate.

Endotoxin dissociated into subunits by sodium deoxycholate treatment exhibited diminished capacity to kill chick embryos, protect mice against the lethal effects of infection with Salmonella typhi, evoke hemorrhagic necrosis in skin inoculated with epinephrine, prepare for and provoke the dermal Shwartzman reaction, and induce pyrogenic tolerance. Surfactant-treated material which had been allowed to reaggregate displayed activity equivalent to that of untreated material. These findings were consistent with the working hypothesis that a macromolecular complex of critical size is required in order for endotoxin to elicit its characteristic effects in the host.

Animals↗