The susceptibility of mice to bacterial endotoxins.
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Albino mice (Rockefeller NCS strain) raised and maintained free of ordinary bacterial pathogens, as well as of intestinal Escherichia coli and of Proteus bacilli, were found to be highly resistant to the lethal effect of bacterial endotoxins. When newborn mice of this NCS colony were nursed by foster mothers from another colony raised under ordinary conditions (SS colony from which the NCS colony was derived), they acquired the intestinal flora of the latter animals and became susceptible to the lethal effects of endotoxins. NCS adult mice could be rendered susceptible to the lethal effect of endotoxins by vaccination with heat killed Gram-negative bacilli. The susceptibility thus induced exhibited a certain degree of specificity for the bacterial strain used in vaccination. Although untreated NCS mice were resistant to the lethal effect of endotoxins, they proved exquisitively susceptible to the infection-enhancing effect of these materials. For example, 1 microg. or less of endotoxin was found sufficient to help establish a rapidly fatal septicemia with Staphylococcus aureus. Small amounts of endotoxin (1 microg. or less), administered alone, caused a marked but transient loss of weight. Vaccination with heat-killed Gram-negative bacilli or with killed BCG increased the resistance of NCS mice to the infection-enhancing effect of small amounts of endotoxin. This protective effect exhibited a certain degree of specificity for the bacterial strain from which the toxin used in the infection-enhancing test was derived. These various findings can be explained by assuming that the pathological effects of endotoxins involve at least two unrelated mechanisms; (a) a primary toxicity illustrated in this study by the loss of weight and enhancement of infection resulting from the injection of small doses of toxin; (b) an immunological reaction with lethal consequences which became manifest only in animals sensitized to the endotoxin by prior exposure to Gram-negative bacilli. (+info)
Studies on the mechanism of the Shwartzman phenomenon. Accelerated cutaneous reactivity to bacterial endotoxins.
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Rabbits given single injections of endotoxin and then skin-tested with endotoxin from 1 day to 1 month later exhibit accelerated skin reactions resembling the Arthus phenomenon. Injection of one endotoxin alters the subsequent reactivity of rabbits to other endotoxins as well. The state of altered reactivity can be transferred with serum, and appears to be related to the presence of non-precipitating cross-reactive antibody, rather than to specific precipitating antibody. (+info)
Effect of exposure of bacteria to endotoxin on their susceptibility to the lethal action of normal serum.
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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. (+info)
The site of action of the Staphylococcus alpha toxin.
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The present study concerns the site of action of the staphylococcus alpha toxin. This powerful necrotizing agent produced by pathogenic strains of staphylococcus is very probably important in the pathogenesis of localized staphylococcus disease and in the shock-like picture sometimes associated with staphylococcus septicemia. Our previous studies had suggested that the toxin has a selective effect on vascular smooth muscle. In investigating this problem further, the following observations were made. 1. The toxin produces an immediate hyperperistalsis and sustained increase in intraluminal tension progressing ultimately to atony and flaccid paralysis in the isolated smooth muscle preparation. 2. The addition of specific antitoxin prior to exposure to toxin prevents this reaction. However, when antitoxin is added after the toxin, no ameliorating effect is seen. 3. The toxin is rapidly and irreversibly bound to its substrate since washing the bowel segment 30 seconds after exposure to toxin fails to change the course of the reaction. 4. Vena caval segments exposed to toxin exhibit a similar initial rise in intraluminal tension followed by flaccid paralysis at which point they no longer respond to epinephrine stimulation. 5. When the toxin is infiltrated in the neighborhood of muscular blood vessels in the living rabbit selective necrosis of smooth muscle cells of the vessel walls is seen. 6. The selective effect on smooth muscle is emphasized by the failure of the toxin to affect the contractility of skeletal and cardiac muscle. 7. Perfusion of the isolated kidney and heart produces an increased resistance to flow after toxin is added to the perfusate. 8. Epithelial cells and fibroblasts in tissue culture exposed to high concentration of toxin for 2 hours are unaffected in their ability to recover and metabolise. This is in marked contrast to the effect on the smooth muscle preparation. The probability that the toxic effect on smooth muscle cells explains some of the local and systemic effects of staphylococcus infection is discussed. (+info)
Production of vibrio El Tor toxin in a liquid medium.
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Watanabe, Yoshikazu (U. S. Army Medical Center, Japan), and Oscar Felsenfeld. Production of vibrio El Tor toxin in a liquid medium. J. Bacteriol. 82:43-47. 1961.-High toxin titers (as measured by mouth lethality and hemolytic activity) were obtained from culture supernatants of strains of El Tor vibrio isolated from patients in Indonesia. Cultivation of the organism in vitro revealed that the concentration of ferrous ion in the medium was critical for the production of maximal yields of toxin. Toxins produced under appropriate conditions were antigenic in rabbits and produced antibodies capable of neutralizing both the hemolytic and lethal actions in multiple proportion. Suggestive evidence has been obtained that the hemolytic and lethal toxins may be separate molecules. (+info)
Effects of bacterial endotoxin on metabolism. I. Carbohydrate depletion and the protective role of cortisone.
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Mice of different strains were protected against the lethal effect of bacterial endotoxin by concurrent injections of cortisone. Either inadequate amounts of cortisone or excessive quantities of endotoxin voided the protection. Analyses of blood sugar, liver glycogen, muscle glycogen, and total body carbohydrate in the skinned eviscerated carcass were carried out on different strains of mice given endotoxin and/or cortisone. Poisoned animals were virtually depleted of all carbohydrate while mice given cortisone alone had concentrations of carbohydrate from three to four times that of normal mice. Mice given a lethal amount of endotoxin and a protective dose of cortisone had two to three times as much carbohydrate as animals injected with the same amount of endotoxin alone but significantly less than that found in normal mice. Dibenzyline failed to alter the lethal effect of endotoxin and to reduce the carbohydrate loss that accompanied endotoxin administration. Endotoxin, at the dosage level employed, lowered the temperature of mice 2 degrees -3 degrees C. during the first hour or two postinjection and the temperature remained essentially unaltered during the next 4 to 5 hours. Loss in body carbohydrate in endotoxin-poisoned mice cannot be explained, therefore, as the result of an elevated metabolic rate accompanying hyperthermia. Endotoxin prevented the conversion of injected glucose into liver glycogen but not into muscle glycogen. Mouse liver mitochondria, in the presence of endotoxin, released from ATP approximately the same amount of inorganic phosphate as that released in the presence of dinitrophenol. (+info)
The relationship of toxin and antitoxin injection site to tetanus development in the rat.
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The pattern of development of symptoms was studied following injection of 3 MLD (minimum lethal dose) of tetanus toxin in each of the following sites in the rat: vein, muscle, endoneurium, epineurium, spinal cord, subarachnoid space, and subdural space. Similar observations were made when 3 MPD (minimum protective dose) of antitoxin were injected into each of the above sites a few minutes after the intramuscular injection of toxin. Local tetanus followed intramuscular, endoneurial, and epineurial injection of the toxin; blood-borne tetanus also appeared in the latter instance. Tetanus dolorosus followed intraspinal injection of toxin. Both dorsal tetanus and blood-borne tetanus developed after subdural administration of toxin. Blood-borne tetanus, alone, appeared following intravenous and subarachnoid injection of toxin. In no case did injection of antitoxin at the various sites listed above prevent local tetanus from developing after intramuscular injection of toxin. Of the various sites injected with antitoxin, the intramuscular, intraspinal, and intravenous were the most effective. It is suggested that the endoneurial tissue spaces serve as a conduit for tetanus toxin from the muscle to the CNS. The perilemma of the peripheral nerve trunk may act as a selectively permeable membrane which permits tetanus toxin to pass from the epineurium to the endoneurium. Outward diffusion of toxin from the endoneurial spaces is apparently markedly reduced. The antitoxin probably is prevented from permeating this barrier in either direction. The importance of absorption of tetanus toxin by the lymphatic and blood circulation is discussed. (+info)
Antigens of Bordetella pertussis. II. Purification of heat-labile toxin.
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Banerjea, A. (Rocky Mountain Laboratory, Hamilton, Mont.) and J. Munoz. Antigens of Bordetella pertussis. II, Purification of heat-labile toxin. J. Bacteriol. 84:269-274. 1962.-A mild method of separating heat-labile toxin of Bordetella pertussis from other cellular components is described; it consists of absorbing toxin on a diethylaminoethyl cellulose column and eluting it with a gradient concentration of NaCl. Toxin preparations thus obtained consisted mainly of protein; their toxicity was destroyed by trypsin but not by ribonuclease or deoxyribonuclease. (+info)