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G C Cozad

Publications and source records attributed to G C Cozad.

15 recordsLinked to original sources
PubMed1983

Immunomodulation by Blastomyces dermatitidis: functional activity of murine peritoneal macrophages.

Cell-mediated immunity plays the dominant role in the immune response of mice to Blastomyces dermatitidis infections. Since macrophages play an important role in cell-mediated immunity, the interactions between sensitized murine peritoneal macrophages and the yeast phase of B. dermatitidis were investigated. Scanning electron microscopy showed that the sensitized macrophages readily phagocytized B. dermatitidis yeast cells. In addition, there appeared to be activation of metabolic pathways within the sensitized macrophages, as indicated by increased chemiluminescence activity during phagocytosis. Sensitized macrophages were significantly better at controlling intracellular proliferation of the yeast cells when compared to nonsensitized cells. This was determined by disruption of macrophages and plating for viable yeasts. Scanning electron microscope observations offered further substantiation. Experiments with Candida albicans indicated that B. dermatitidis non-specifically activated macrophages. At 2 h postphagocytosis, 30% fewer C. albicans in B. dermatitidis-activated macrophages were able to form germ tubes. These studies demonstrated the multiple potential of activated macrophages with regard to their functional activity.

Animals↗
PubMed1982

Immunoadjuvant effects of Blastomyces dermatitidis against EL 4 lymphoma in C57BL/6J mice.

The ability of thimerosal-killed Blastomyces dermatitidis yeast cells, which greatly enhance the cell-mediated immune response in C57BL/6J mice, to act as an immunopotentiator against EL 4 lymphoma was investigated. Mice treated with yeast cells were protected from as many as 10(4) tumor cells. Complete suppression of tumor growth was observed in treated animals that received ip injections of 10(2) or 10(3) tumor cells. The mice, however, were not immune to further EL 4 lymphoma cell challenge. The lack of tumor-specific immunity indicated nonspecific suppression of tumor growth probably by macrophages. Ten days after treatment, the peritoneal macrophages from mice that showed complete tumor suppression were tested for their ability to prevent in vitro tumor cell proliferation. These macrophages demonstrated 90% inhibition of [3H]thymidine incorporation by EL 4 tumor cells at a 100:1 effector-to-target cell ratio. Macrophages from B. dermatitidis-treated animals exhibited a twofold increase in specific lysis of EL 4 at 10 and 15 days compared to resident macrophages. Spleen and lymph node cells from protected animals showed no cytotoxic activity against EL 4 in a 51Cr release assay. Treatment of tumor-bearing mice with a single dose of B. dermatitidis was effective only if administered within 24 hours of tumor establishment. These results demonstrated that nonviable B. dermatitidis prohibits the growth of EL 4 under conditions where Corynebacterium parvum fails to do so.

Animals↗
PubMed1980

Cell-mediated immunoprotection in blastomycosis.

Delayed hypersensitivity can be induced in C57BL/6J mice by two subcutaneous injections of Merthiolate-killed Blastomyces dermatitidis yeast cells in Freund incomplete adjuvant. Development of delayed hypersensitivity peaked at the day 18 post-primary antigen-emulsion injection, as determined by footpad sensitivity tests. Mice rendered hypersensitive to B. dermatitidis were protected from the lethal effect of a blastomyces infection. The protection effects were shown both in mortality tests and in data from organ cultures as expressed by indices of resistance. Data from this study show that there is a close parallel relationship between host resistance and the prevailing level of delayed hypersensitivity.

Animals↗
PubMed1979

Thymosin restoration of cellular immunity to Blastomyces dermatitidis in T-cell-depleted mice.

The immunopotentiating properties of thymosin in thymectomized, lethally irradiated, bone marrow-reconstituted mice (ThyXBM) were characterized, using footpad sensitivity to Blastomyces dermatitidis. Normal mice were shown to exhibit increasing delayed-type hypersensitivity responses to killed yeast cells of B. dermatitidis after injections of the organism on days 0 and 7, as measured by footpad swelling tests. The footpad response of normal thymosin-treated mice was similar to that of normal, non-thymosin-treated mice. ThyXBM mice were unable to elicit a footpad response when similarly injected and footpad tested with B. dermatitidis. Thymosin-treated ThyXBM mice responded to footpad testing at a level that was 62% greater than the response seen in non-thymosin-treated ThyXBM mice. This peak response occurred on day 12. The results indicated that thymosin was unable to enhance immune responses of normal intact mice but could restore immunocompetence in a T-cell-depleted host, as measured by footpad sensitivity to B. dermatitidis.

Animals↗
PubMed1976

The ethanol fractionation of mouse serum.

A method for the ethanol fractionation of normal mouse serum has been developed which is rapid and simple to perform. The method was shown to be effective in purification of IgG1, IgG2 and gammaM-gammaA globulins. Gel filtration and zone electrophoresis proved to be effective in separating the gammaM-gammaA globulin combination into their respective components. Immunoelectrophoresis was chosen to assess the homogeneity of the fractions and the results agree with those obtained by other workers.

Animals↗
PubMed1975

Antiglobulin factors in normal mouse serum reacting with enzyme-digested gamma globulin.

The presence of antiglobulin factors in normal mouse serum was studied. Mice were injected with human 0 Rh(+) erythrocytes and the resulting gamma globulins were digested with papain. The reaction was demonstrated by agglutinations of human 0 Rh (+) perythryocytes sensitized with the Fab fragments when treated with normal mouse serum. Studies suggested that there are two factors in mice, a 7S AND A 19S globulin form. Cross-reactivity between strains of mice was demonstrated.

ABO Blood-Group System↗
PubMed1974

Passive transfer of delayed hypersensitivity to Blastomyces dermatitidis between mice.

This study further characterized the delayed hypersensitivity state induced in animals by Blastomyces dermatitidis exposure. Passive transfer of delayed hypersensitivity by transfer of cells and inhibition of migration of peritoneal exudate cells were studied, using sensitized mice of two inbred strains. Donor mice were subcutaneously inoculated with viable B. dermatitidis yeast cells. After 15 days, spleen cells or serum from these animals were injected intravenously into normal recipients of the same strain. After 24 h these mice were footpad tested with killed B. dermatitidis yeast cell antigen. Mice receiving spleen cells from sensitized animals had a significant increase in footpad thickness 24 to 48 h after testing. Those receiving only serum remained negative. Migration of peritoneal exudate cells from blastomyces-sensitive donor mice was inhibited by presence of blastomycin but not by mycobacterial antigen. Neither blastomyces-sensitive nor control animals reacted to footpad or migration inhibition testing with mycobacterial antigen.

Animals↗
PubMed1974

Effect of cyclophosphamide on Histoplasma capsulatum infections in mice.

Mice were injected intraperitoneally (i.p.) with 300 mg of cyclophosphamide (CY)/kg of body weight, and 24 h later were injected i.p. with varying dosages of yeast-phase cells of Histoplasma capsulatum. At specific time intervals organs were removed, ground, and cultured to determine the number of viable organisms contained in the spleen, liver, and lungs. Injection of mice with CY was found to cause a dramatic increase in the numbers of parasites isolated from these organs when compared with non-drug-treated controls. Mice given 10(7) yeast cells showed the largest increase in colony numbers. A greater than fivefold increase in the numbers of organisms isolated from the spleens of CY and 10(3) yeast cell-treated mice, as compared with non-drug-treated animals, was observed at all time periods. The general trend for infected control animals was a decrease in colony numbers. All mice given CY plus 10(7) yeast cells intravenously (i.v.) died by day 20 postinfection. Mice given CY and 10(7) yeast cells i.p. showed no evidence of fatal Histoplasma infection. Deaths occurring by day 5 in CY-treated animals injected with H. capsulatum yeast cells i.v. or i.p. were considered due to bacterial infection or toxicity, or both. Hepatosplenomegaly was observed in mice treated with CY and 10(7) yeast cells of H. capsulatum. Enlarged lungs were also noted. CY control mouse spleens weighed 30% less than normal spleens. Organs of animals injected with H. capsulatum alone did not vary significantly from those of normal mice. Complete drug-induced suppression of humoral antibody response was achieved for 10 days, as determined by hemagglutination titrations.

Animals↗
PubMed1973

Role of delayed hypersensitivity in blastomycosis of mice.

C57BL/6J mice rendered hypersensitive to Blastomyces dermatitidis were protected from the lethal effects of a blastomyces infection. This protection was observed following a lethal intraperitoneal challenge with viable cells 15 days after subcutaneous inoculation with 3.9 x 10(4) viable cells. Delayed hypersensitivity was induced in C57 mice by two injections of Merthiolate-killed cells in adjuvant or by a single injection of viable cells. Development of hypersensitivity was determined at appropriate intervals by footpad injection with killed yeast cells.

Animals↗
PubMed1972

Immunological unresponsiveness induced by cryptococcal capsular polysaccharide assayed by the hemolytic plaque technique.

Numerous studies have suggested that cryptococcal capsular polysaccharide could induce an immunological paralysis. To investigate this possibility, mice were given various concentrations of purified cryptococcal polysaccharide and then 14 days later were challenge-immunized with the same material in Freund's incomplete adjuvant. Anticryptococcal agglutinin titers were determined at various periods after polysaccharide treatment and after challenge immunization. At the same periods the hemolytic plaque technique was used to determine the number of spleen cells capable of producing antibody against cryptococcal polysaccharide. The data indicated that there was a transitory immune response which preceded tolerance induction. In animals given the largest doses of polysaccharide, "in vivo" neutralization was responsible for low serum agglutinin titers during the transitory response. The capsular polysaccharide was considered to have induced immunological unresponsiveness at the highest concentration, because challenge immunization did not stimulate an increase in the number of plaque-forming cells (PFC). A sixfold increase in numbers of PFC was found in animals injected initially with the lowest concentration of polysaccharide. These results support the idea that tolerance was due to terminal differentiation without proliferation of the immunocompetent cells. The central failure of the immune mechanism which was apparent in the paralyzed mice was temporary under the conditions of this experiment.

Agglutination Tests↗
PubMed1969

Effect of antilymphocyte serum on animals experimentally infected with Histoplasma capsulatum or Cryptococcus neoformans.

The anti-mouse and anti-guinea pig antilymphocyte sera (ALS) prepared for this study were shown to contain cytoxic and leucoagglutinating antibodies, and were capable of producing severe lymphopenia in these animals. Guinea pigs treated weekly with ALS were more susceptible to development of fatal infection when inoculated with Histoplasma capsulatum. No fatalities occurred in guinea pigs infected with equal doses of H. capsulatum but treated with normal rabbit serum (NRS) or saline. The time necessary to reach 50% fatality in mice infected with Cryptococcus neoformans was greatly reduced by pretreatment with ALS in comparison with infected controls treated with NRS or saline. When low dosages were used (0.1 ld(50)), the effect was even more pronounced. Spleen homogenates from mice infected with equal dosages of H. capsulatum and treated with ALS or NRS were cultured. More than 150 times as many organisms were present in the spleens of the ALS-treated group. Similar results were obtained from culturing the lungs and liver. Delayed hypersensitive skin reactions were radically decreased or abrogated in H. capsulatum-infected guinea pigs inoculated intraperitoneally with ALS 12 hr before skin testing with histoplasmin. When ALS was given weekly, the influence on skin reactivity was less notable. Given intradermally, ALS was shown to inhibit the delayed reaction to histoplasmin within a radius of 40 mm.

Animals↗
PubMed1969

Effect of histoplasmosis on antibody response to an erythrocyte antigen.

Infection of mice with Histoplasma capsulatum depressed their ability to form agglutinins against foreign erythrocytes. Animals previously inoculated with 10(8) yeast cells of H. capsulatum showed the most significant depression, occurring when erythrocytes were injected 8 days after infection. The average log(2) hemagglutinin titer was 2.7 compared to 8.0 for the control (noninfected) group. In general, depression of hemagglutinin response in all infected mice was greatest 8 days after infection, but response was back to near normal after 16 days and stayed at that level for the remaining time tested (24 days).

Animals↗
PubMed1966

Immunoelectrophoretic studies of sera from rabbits exprimentally infected with Histoplasma capsulatum.

Adamson, David M. (University of Oklahoma, Norman), and George C. Cozad. Immunoelectrophoretic studies of sera from rabbits experimentally infected with Histoplasma capsulatum. J. Bacteriol. 92:887-891. 1966.-In a study involving 24 mature Dutch rabbits inoculated intravenously with 2.6 x 10(8)Histoplasma capsulatum yeast cells per kg of body weight, all rabbits were shown to develop precipitins by the end of the 5th week. Precipitins were demonstrated both by the micro-Ouchterlony method and microimmunoelectrophoresis with the use of concentrated histoplasmin as the antigen. The latter technique proved to be the more sensitive. The 10 x concentrate of histoplasmin gave better precipitin patterns than did the 5 x concentrate. Agglutinins were formed by 90% of the rabbits by the end of the 4th week, as shown by the capillary tube agglutination test. Three precipitin bands, arbitrarily designated A, B, and C, were demonstrated by immunoelectrophoresis with use of the sera of the test animals. Band A occurred between the 1st and 2nd weeks after inoculation and was, for a period, present in 100% of the sera of the test animals. Band A occurred separately or in conjunction with band B or B and C, and it persisted longer than these other two bands. Bands B and C appeared between the 3rd and 4th weeks and were found, by the end of the 5th week, in 35 and 15%, respectively, of the sera tested. They were never seen separately or together without the presence of band A. Band C disappeared by the end of the 6th week, and band B, by the 10th week, but band A was still present in 19% of the sera at the end of 10 weeks.

Animals↗