PubMed Health⌕ Search

Biomedical subjects

M LANDY

Publications and source records attributed to M LANDY.

At least 37 records · Page 2Linked to original sources

Preparation and host-reactive properties of endotoxin with low content of nitrogen and lipid.

Endotoxins of low lipid content prepared from S. enteritidis by the aqueous ether method have been further treated to remove bound lipid by non-hydrolytic procedures. Such endotoxins, containing as little as 2 per cent lipid A, were as potent in stimulating a variety of physiological responses as those prepared by the well known phenol-water or Boivin procedures which yield products containing as much as 30 per cent lipid A. To verify the difference in lipid content between the aqueous ether preparations and other types of endotoxins, three different methods of lipid analysis were employed: determination of chloroform-soluble material released by hydrolysis with hydrochloric acid (lipid A) or with acetic acid (lipid W), and estimation of total bound fatty acids. These methods were in accord in showing the magnitude of the difference. No more than one-half of the fatty acids present in endotoxin were associated with the fraction designated lipid A. Methods are described for the preparation of potent endotoxins with analytical values for nitrogen, phosphorus, hexosamine, carbohydrate, and fatty acid which do not differ appreciably from those of the classical, non-toxic, haptenic polysaccharides.

Antitoxins↗

Biological properties of parent endotoxins and lipoid fractions, with a kinetic study of acid-hydrolyzed endotoxin.

The biological potencies of a number of lipid fractions separated from endotoxins by acid hydrolysis, including the material known as lipid A, were determined in parallel with those of their parent endotoxins, employing bio-assays based on the following dose-related host responses: fever, resistance to infection, tumor damage, primary inflammation of skin, and lethality. Without exception, lipid fractions dispersed by detergents exerted less than 1 per cent of the biological activity of the potent endotoxins from which they were derived. A study was made of the rate at which biologic activities diminished in relation to the release of bound lipid during progressive hydrolysis of Salmonella enteritidis endotoxin with dilute acid. Each of the five assays for endotoxin revealed that biological activity had been reduced to negligible proportions prior to any significant liberation from the endotoxin of water-insoluble firmly bound lipid. The major pharmacological activity of endotoxins, therefore, is acid-labile and cannot be accounted for in isolated lipids. This conclusion is also supported by the finding that lipids with activity similar to that of lipid A could be obtained by non-hydrolytic methods without diminishing the potency of the parent endotoxins.

Antitoxins↗

Studies on infection and immunity in experimental typhoid fever. III. Effect of prophylactic immunization.

A study was made of the efficacy of various antityphoid immunizing agents in immunizing chimpanzees against typhoid fever produced by feeding viable S. typhosa. It was found that both acetone-killed and heat-killed, phenol-preserved typhoid vaccines were effective in protecting against infection induced with either homologous or heterologous strains of typhoid bacilli. Purified O antigen induced no discernible protection, but some immunity was afforded by the administration of purified Vi antigen.

Animals↗

Effect of exposure of bacteria to endotoxin on their susceptibility to the lethal action of normal serum.

Michael, J. Gabriel (National Cancer Institute, Bethesda, Md.), and Maurice Landy. Effect of exposure of bacteria to endotoxin on their susceptibility to the lethal action of normal serum. J. Bacteriol. 82:257-264. 1961.-The uptake of typhoid endotoxin by Escherichia coli and Shigella dysenteriae was investigated with respect to its effect on the susceptibility of these strains to the bactericidal action of serum. The attachment of endotoxin to the organisms was found to be dependent on time, temperature, concentration, and the physiological state of the bacteria. Short exposure leading to the adsorption or incorporation of small amounts of endotoxin enhanced the lethal effect of serum, whereas long periods of exposure leading to the uptake of larger amounts rendered the bacteria relatively resistant.

Antitoxins↗

Studies on infection and immunity in experimental typhoid fever. I. Typhoid fever in chimpanzees orally infected with Salmonella typhosa.

A disease resembling human typhoid fever has been induced by feeding live cultures of Salmonella typhosa to young chimpanzees, thus confirming the classical reports of Grünbaum and of Metchnikoff and Besredka. Detailed clinical observations, results of stool and blood cultures, and serological studies have confirmed the impression that the disease produced in chimpanzees closely resembles the mild form of human typhoid fever frequently seen in childhood. Gross and histologic examination of intestines, mesenteric lymph nodes, liver, spleen, and other organs of orally infected chimpanzees has demonstrated that the pathological findings are essentially indistinguishable from those seen in mild typhoid fever in man. The clinical spectrum of disease seen in chimpanzees ranged from moderately severe illness, through transitory illness, to afebrile infection with or without bacteriemia (but invariably with an antibody response), occasionally leading to the development of persisting biliary infection and the carrier state. Thus the range of illness observed in chimpanzees resembled that seen in man, except that the severe and complicated forms of typhoid fever were not observed in the chimpanzee. A reason for this difference is proposed and discussed. In contrast to the limitations imposed upon the interpretation of human epidemiologic observations, it has been possible to demonstrate in the chimpanzee that clinical variation in disease pattern from animal to animal may occur despite the administration of the same dose of the same bacterial strain simultaneously to an entire group of animals under study; in other words, variation in clinical pattern is dependent on inherent, non-specific host factors as well as on dose, strain or preceding state of immunity. Variation in dose and in challenge strain of S. typhosa employed also appeared to have an effect upon the likelihood of producing febrile as against afebrile infection in chimpanzees. The dose required to produce clinical disease, even with the more virulent strain, was excessively large compared to what is believed to be the dose required to produce illness in man; the limitations of this assumption, and suggested explanations for the findings, are discussed. The production of the spectrum of typhoid fever in the chimpanzee has made possible the study of basic problems in this disease which are not amenable to definitive study through the use of prevailing laboratory techniques.

Animals↗

Inactivation of endotoxin by a humoral component. IV. Alteration in the immunological properties of typhoid endotoxin.

The immunological properties of typhoid endotoxin were investigated after incubating it with serum under conditions in which EDC (endotoxin-detoxifying component) was operative. Brief interaction of endotoxin in vitro with this system in serum (human, rabbit, mouse) abolished its antigenicity for rabbits. Suitable modification of the host permitted separate elicitation of toxic and antigenic responses to typhoid endotoxin. Endotoxin altered by EDC was still capable of precipitating specific antibody; moreover, it did so in a manner which resembled that of the haptenic polysaccharide.

Animals↗