CHARACTERIZATION OF THE PYROGENICITY OF CANDIDA ALBICANS, SACCHAROMYCES CEREVISIAE, AND CRYPTOCOCCUS NEOFORMANS.
(49/303)
Kobayashi, George S. (Tulane University, New Orleans, La.), and Lorraine Friedman. Characterization of the pyrogenicity of Candida albicans, Saccharomyces cerevisiae, and Cryptococcus neoformans. J. Bacteriol. 88:660-666. 1964.-The intravenous injection into rabbits of 10(9) yeast cells of Candida albicans, Saccharomyces cerevisiae, or Cryptococcus neoformans (both slightly and heavily encapsulated forms) induced a febrile response indistinguishable from that elicited by gram-negative bacterial endotoxin. There was a brisk rise in body temperature which began as early as 30 min after injection, peaked once or twice, and then returned to normal after about 10 hr. With viable C. albicans, the febrile response did not return to normal but remained elevated for several days and terminated at death of the animal. Of three extraction procedures employed in attempts to isolate the endotoxin-like pyrogenically active substances from C. albicans, only one, the phenol extraction method, was successful. Pyrogenic substances were more easily extractable from S. cerevisiae, but extracted cells of both species were still highly pyrogenic. It was concluded that the particulate nature of the yeast cell did not contribute to the induction of fever, for latex particles of a similar size were nonpyrogenic. Viable or heat-killed C. albicans, phenol extract of C. albicans, zymosan, and polystyrene latex particles all failed to induce in rabbits increased dermal reactivity to epinephrine. (+info)
SOME CYTOLOGICAL AND PATHOGENIC PROPERTIES OF SPHEROPLASTS OF CANDIDA ALBICANS.
(50/303)
Kobayashi, George S. (Tulane University, New Orleans, La.), Lorraine Friedman, and Judith F. Kofroth. Some cytological and pathogenic properties of spheroplasts of Candida albicans. J. Bacteriol. 88:795-801. 1964.-Spheroplasts of Candida albicans were prepared by use of an enzymatic mixture from the digestive tract of the snail Helix pomatia. Untreated cells exhibited well-defined cell walls, whereas such structures were absent from spheroplasts. The intravenous inoculation of either spheroplasts or intact cells into rabbits produced a fever which was apparent within 30 min, the "immediate" fever response characteristic of microbial endotoxin. Cell-wall fragments of enzyme-treated cells did not induce a convincing pyrogenic response. When the inoculum was viable, body temperatures did not return to normal but remained elevated until death of the animal 1 or more days later, exhibiting the "delayed" fever of infection. The gross pathological picture in animals succumbing to infection by viable spheroplasts was similar to that obtained with untreated yeast cells. (+info)
STUDIES ON BACTERIAL PYROGENICITY. 3. SPECIFICITY OF THE UNITED STATES PHARMACOPEIA RABBIT PYROGEN TEST.
(51/303)
The specificity of the first or "presumptive" portion of the USP rabbit pyrogen test was investigated by use of a new absolute standard of reference. The reference standard was a 0.9% sodium chloride solution prepared to be pyrogen-free. Details of the preparation were described. The hypothesis was explored that the temperature response of rabbits after intravenous injection of the standard solution was independent of exogenous pyrogen. Reactions observed among the rabbits in our colony allowed a classification of these animals ranging from "consistently reliable" to "consistently unreliable." Details of the experimental results and implications for pyrogen testing are discussed. The recommendation was made that all rabbit test animals be "screened" in sham and actual tests before being used for pyrogen testing. (+info)
HOST-PARASITE RELATIONSHIPS AMONG GROUP A STREPTOCOCCI. 3. DEPRESSION OF RETICULOENDOTHELIAL FUNCTION BY STREPTOCOCCAL PYROGENIC EXOTOXINS.
(52/303)
Hanna, Edgar E. (University of Minnesota, Minneapolis), and Dennis W. Watson. Host-parasite relationships among group A streptococci. III. Depression of reticuloendothelial function by streptococcal pyrogenic exotoxins. J. Bacteriol. 89:154-158. 1965.-Measurement of the rate of clearance of colloidal carbon from the circulating blood is an effective and simple technique for assessing the functional state of the reticuloendothelial system (RES) of experimental animals. This paper concerns a study of the RES function in rabbits after treatment with streptococcal pyrogenic exotoxins. Intravenous injection of 1.0 ml of the toxin produced by a strain of type 18, group A streptococcus caused a prolonged (at least 24 hr) depression of RES function. The activity at 48 hr after toxin injection was about equal to that in control animals. Repeated intravenous injections of the toxin abolished the initial depressing effect on RES function, but did not cause stimulation. In comparison, intravenous injection of equivalent doses of endotoxin prepared from Escherichia coli COO8 also caused an initial depression of RES function; however, in contrast with the effect of exotoxin, stimulation occurred as early as 24 hr and was about twice as active at 48 hr. The prolonged depression by streptococcal pyrogenic exotoxin is suggested as one means by which this toxin potentiates lethality and tissue damage by other toxins such as streptolysin O and endotoxins from gram-negative bacteria. (+info)
STUDIES ON TUBERCULIN FEVER. 3. MECHANISMS INVOLVED IN THE RELEASE OF ENDOGENOUS PYROGEN IN VITRO.
(53/303)
In a search for the source of the circulating endogenous pyrogen (EP) that mediates tuberculin-induced fever, tuberculin was incubated in vitro with various tissues of rabbits sensitized by intravenous infection with BCG. Evidence was obtained that tuberculin specifically stimulates cells in the blood of sensitized rabbits to generate pyrogen in vitro, whereas both lymph node and spleen cells from the same donors were inactive. Since normal blood cells, incubated in plasma of sensitized donors, were similarly activated, it is postulated that circulating antibodies play a role in sensitizing cells (presumably granulocytes) to release pyrogen on contact with tuberculin) both in vitro and in vivo. Release of endogenous pyrogen in vitro may be a sensitive means of detecting immunologic reactions between antigen and specifically sensitized blood cells-in other allergic states accompanied by fever. (+info)
THE PRESENCE OF ENDOGENOUS PYROGEN IN NORMAL RABBIT TISSUES.
(54/303)
Saline extracts of homogenized, uninfected, rabbit tissues produced febrile responses when injected intravenously into rabbits. Extracts of muscle, lung, and heart evoked fevers that were similar to those induced by leucocyte pyrogen; extracts of spleen, liver, and kidney caused more sustained fevers. The minimal pyrogenic dose appeared to be between 1.5 and 3 gm wet weight of tissue. Evidence is presented that neither Gram-negative bacterial endotoxin nor polymorphonuclear leucocytes (circulating or sequestered in the tissues) can be implicated as the source of pyrogen in tissue extracts. It seems likely, therefore, that a pyrogenic material of truly endogenous origin is widely distributed in tissues. Tissue pyrogen appears to be a large molecule which is relatively resistant to treatment with acid but not with alkali. Possible pathological roles for this endogenous agent (or agents) are briefly indicated. (+info)
MECHANISMS OF ENDOTOXIN TOLERANCE. 3. THE REFRACTORY STATE DURING CONTINUOUS INTRAVENOUS INFUSIONS OF ENDOTOXIN.
(55/303)
Bacterial endotoxins were administered by continuous intravenous infusions at constant rates to normal man and rabbits. An initial progressive febrile reaction was followed by progressive defervescence to baseline. The resulting pyrogenic refractory state was characterized as follows: (a) reticuloendothelial blockade with thorotrast neither prevented nor reversed its course; (b) passive transfer was unsuccessful with refractory phase plasma; (c) infusions of normal plasma or fresh whole blood failed to restore responsiveness; (d) a minimum of 4 hours of continuous endotoxin infusion was required for full development of unresponsiveness; (e) circulating antibody titers to endotoxin remained unaltered; (f) peripheral leukocytosis appeared; (g) infusion of febrile phase plasma reevoked an immediate, monophasic fever; (h) endotoxinemia could be demonstrated by pyrogen bioassay; (i) 10-fold increases in endotoxin infusion rates reevoked fever; (j) impaired responsiveness extended to heterologous endotoxins; (k) dermal inflammatory responses to endotoxin were suppressed in man while tuberculin reactivity remained unimpaired; dermal inflammatory responses to endotoxin were enhanced in rabbits; and (l) pyrogenic reactivity to endotoxin reappeared within 24 hours in man; refractoriness persisted in rabbits. It is concluded that the pyrogenic refractory state reflects an inability of the host to continue to mobilize endogenous pyrogen during sustained endotoxinemia. Such observations, together with previous studies, are consistent with two distinct immunologic mechanisms of resistance to endotoxin pyrogenicity: (a) desensitization at the cellular level; and (b) elaboration of circulating antibodies which assist reticuloendothelial clearance and destruction of endotoxin. Whereas both such mechanisms may contribute to pyrogenic tolerance, the characteristics of the pyrogenic refractory state suggest the participation only of the former. (+info)
The international pyrogen reference preparation.
(56/303)
In accordance with authorization given by the WHO Expert Committee on Biological Standardization in 1950, the National Institute for Medical Research, London, obtained samples of two bacterial pyrogens and arranged for an international study of their pyrogenic properties in rabbits. The results of this study showed that the dose response curves were flat and there was a large variation in response within and between colonies of rabbits.It was agreed that some reference preparation was needed. There was no evidence to indicate the most suitable type of preparation, and there was insufficient as regards either of the two which had been studied. It was therefore decided to make available a quantity of a preparation of the O somatic antigen of Shigella dysenteriae for the International Reference Preparation. Such a substance has been obtained for this purpose and the distribution and characteristics are described. (+info)