PubMed Health⌕ Search

Biomedical subjects

D W WATSON

Publications and source records attributed to D W WATSON.

At least 19 recordsLinked to original sources
PubMed1965

MODIFICATION OF HOST RESPONSES TO BACTERIAL ENDOTOXINS. II. PASSIVE TRANSFER OF IMMUNIY TO BACTERIAL ENDOTOXIN WITH FRACTIONS CONTAINING 19S ANTIBODIES.

Serum from rabbits rendered tolerant or immune to 100 MPD-3/kg of endotoxin when passively transferred to normal rabbits gave partial tolerance to the standard dose of endotoxin. The same serum was fractionated by DEAE chromatography into 4 major fractions. Immunoelectrophoretic analysis indicated that the 7S gamma(2)-and the 19S gamma(1)-immunoglobulins were separated into two distinct fractions. Of the four fractions tested, only fraction IV containing 19S gamma(1)-immunoglobulm conferred complete pyrogenic tolerance to 100 MPD-3/kg of endotoxin. Additional fractionation of DEAE fraction IV by exclusion chromatography on sephadex G-200 gave 3 fractions. Of these only the first, containing 19S gamma(1)-immunoglobulin conferred complete pyrogenic and lethal tolerance to normal rabbits. There was no correlation between the quantity of O-specific antibodies and the ability to transfer tolerance. It is concluded that endotoxin tolerance involves a classical immune mechanism which includes both 19S gamma(1)-immunoglobulin specific for toxophore groups common to many endotoxins and a normally functioning RES. To avoid confusion with immunologic tolerance, it is suggested that the term endotoxin immunity be substituted for endotoxin tolerance.

Animals↗
PubMed1965

HOST-PARASITE RELATIONSHIPS AMONG GROUP A STREPTOCOCCI. 3. DEPRESSION OF RETICULOENDOTHELIAL FUNCTION BY STREPTOCOCCAL PYROGENIC EXOTOXINS.

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.

Animals↗
PubMed1964

HOST-PARASITE RELATIONSHIPS AMONG GROUP A STREPTOCOCCI. I. HYALURONIC ACID PRODUCTION BY VIRULENT AND AVIRULENT STRAINS.

Willoughby, Donald S. (University of Minnesota, Minneapolis), Yael Ginzburg, and Dennis W. Watson. Host-parasite relationships among group A streptococci. I. Hyaluronic acid production by virulent and avirulent strains. J. Bacteriol. 87:1452-1456. 1964.-Intradermal passage of group A streptococcal strains in rabbits is an easy and effective technique for selecting organisms capable of producing increased amounts of hyaluronic acid. Glutamine was required for in vitro hyaluronate production, although the requirement varied with the organism tested. The virulent type 18 cells produced maximal amounts of hyaluronic acid in the presence of 0.01% glutamine compared with 0.1% for the more avirulent type 28; after animal passage, the glutamine requirement for type 28 decreased to 0.01%. Organisms selected by animal passage produced small quantities of hyaluronic acid in the absence of an exogenous source of glutamine. Glucose at a concentration of 1% gave the greatest stimulation for hyaluronate formation. Growth studies indicated similar rates of multiplication for types 18 and 28; yet, the rate of hyaluronate production under these conditions was much greater for the more virulent type 18. Because of these observations, it is suggested that the rate of hyaluronate production is a contributing factor in the virulence of type 18.

Animals↗
PubMed1964

HOST-PARASITE RELATIONSHIPS AMONG GROUP A STREPTOCOCCI. II. INFLUENCE OF SEX ON THE SUSCEPTIBILITY OF INBRED MICE TOWARD STREPTOCOCCAL INFECTION.

Willoughby, Donald S. (University of Minnesota, Minneapolis), and Dennis W. Watson. Host-parasite relationships among group A streptococci. II. Influence of sex on the susceptibility of inbred mice toward streptococcal infection. J. Bacteriol. 87:1457-1461. 1964-BALB/Sy mice showed marked sex differences in susceptibility to a strain of Streptococcus pyogenes type 18. Castration of the highly susceptible normal adult male increased their resistance 1,000-fold, which approximated that of normal female mice. Treatment of male mice with estrogen and stilbestrol did not affect their resistance significantly. Young, sexually immature male mice, 4 weeks old, were more resistant than mature males. Susceptibility of the resistant females was not affected by age or bilateral ovariectomy, but testosterone injections caused an increase in susceptibility. Treatment of male mice with estrogen and stilbestrol did not modify their resistance. Smears of peritoneal exudates from normal male mice after intraperitoneal injection of streptococci revealed rapid multiplication of the organisms. There was no evidence of multiplication in the resistant normal female and castrated male mice.

Allergy and Immunology↗
PubMed1963

MODIFICATION OF HOST RESPONSES TO BACTERIAL ENDOTOXINS. I. SPECIFICITY OF PYROGENIC TOLERANCE AND THE ROLE OF HYPERSENSITIVITY IN PYROGENICITY, LETHALITY, AND SKIN REACTIVITY.

Evidence is presented suggesting that the apparent non-specificity of pyrogenic tolerance observed with Gram-negative bacterial endotoxins is due to related antigenic determinants associated with the macromolecular toxins. This is based on results obtained in rabbits from pyrogenic cross-tolerance tests with selected endotoxins. In these tests, purified endotoxins from Escherichia coli (COO8) and Chromobacterium violaceum (CV) gave results one might expect with non-reciprocal cross-reacting antigens in classical immune systems. Additional evidence for an immune mechanism in tolerance is suggested by the highly significant anamnestic response observed. Lipid A, a toxic derivative of the purified COO8 endotoxin, failed to induce pyrogenic tolerance against the parent toxin. These results are explained by assuming that endotoxins have two interdependent activities associated with different portions of the macromolecule; one is assumed to be responsible for the primary toxicity, and the other is involved in secondary toxicity. The latter is dependent on the hypersensitive state of the host. Additional evidence for the role of hypersensitivity in secondary toxicity is based on the observation that adult rabbits are highly sensitive to the pyrogenic, lethal, and skin-reacting activities of endotoxin in contrast to young animals which are more resistant to all of these attributes of toxicity. In adults, the host responses to pyrogenicity, lethality, and skin reactivity could be partially inhibited by the early exposure of the animals to massive doses of endotoxin equivalent to a LD(50). The pyrogenic tolerance shown in these animals was specific indicating that the inhibition of the hypersusceptibility to endotoxin involved an immunological mechanism. A mechanism of endotoxin tolerance is proposed and discussed based on the induction of specific antibodies capable of assisting the RES in the clearance and destruction of endotoxin. It is suggested that the present inconsistencies relative to the chemical nature and biological activities of endotoxins might be explained on the basis of these two activities and the failure to recognize the importance of the immunological state of the host in which the toxins are tested.

Animals↗
PubMed1962

Antibody-producing capacity of adult chicken spleen cells in newly hatched chicks.

1. To evaluate the effect of primary in vitro antigenic stimulation on a population of immunologically competent cells, a homologous cell transfer system was used, with adult chickens as the spleen cell donors, killed Brucella abortus as the antigen, and newly hatched chicks as the recipients. 2. The distribution of antibody titers in recipients of cells from random donors was bimodal, with about 30 per cent showing no detectable titer and the remainder distributed normally. 3. Variability of titer was reduced significantly in subgroups receiving cells from a single donor, indicating that the primary source of variability was the genetic capacity of discrete cell populations to respond to antigen. 4. In serial passage studies, activity of donor cell populations was lost rapidly: antibody was not demonstrated after the second passage, and the graft versus host reaction (splenomegaly) was not demonstrated after the third passage. Results were similar with in vitro antigenic stimulation at the time of the first passage only and with additional stimulation at the time of subsequent transfers. 5. The thesis that,the homograft reaction of the newly hatched recipients had contributed significantly to the variability in the single transfer studies and to the rapid loss of activity in the serial transfer experiments was confirmed by the results of transfers following alteration of the lymphoreticular system of the host by thorotrast administration, splenectomy, and treatment with 19-nortestosterone during embryogenesis. All three favored the survival and function of transferred cells, raising the average antibody titer and virtually eliminating the no-response category. The inhibition of homograft immunity was most pronounced in the 19-nortestosterone group.

Animals↗
PubMed1960

Host-parasite factors in group A streptococcal infections. A comparative study of streptococcal pyrogenic toxins and gram-negative bacterial endotoxin.

THE DATA PRESENTED IN THIS STUDY SUGGEST THAT GROUP A STREPTOCOCCI PRODUCE TWO DISTINCT PYROGENIC TOXINS: one primarily an intracellular toxin and the other mainly an extracellular toxin. Both of these toxins are not extractable by the conventional methods, phenol and TCA, used for isolation of Gram-negative bacterial endotoxin. Their chemical composition, therefore, differs from that of Gram-negative bacterial endotoxin. On the basis of tolerance studies it appears that similar non-specific host factors may be involved in the detoxification of both the streptococcal intracellular pyrogenic toxin and the Gram-negative bacterial endotoxin. Detoxification of streptococcal exotoxin requires a more immunologically specific mechanism. Because all the Group A sonic extracts studied elicited reciprocal tolerance to one another, it is suggested that tolerance to the intracellular pyrogenic toxin is not correlated with type-specificity.

Animals↗