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Biomedical subjects

A G Osler

Publications and source records attributed to A G Osler.

At least 19 recordsLinked to original sources
PubMed1979

Effect of cobra venom factor on the response of Wistar-Furth rats to the Gross-virus-induced (C58NT)D lymphoma.

Wistar-Furth rats were injected with the anticomplementary cobra venom factor at the time of challenge with the Gross-virus-induced (C58NT)D lymphoma. Complement depletion and/or activation of the complement system in these animals led to the following findings: Multiplication of the tumor cells in vivo was accelerated and mortality rates were enhanced. In addition, serum levels of the immunoglobulins which mediate antibody-dependent cellular cytotoxicity were depressed.

AKR murine leukemia virus↗
PubMed1978

The application of complement fixation to antibody weight estimates I. To soluble antigens.

A method is described for estimating early mouse IgG antibodies to the dinitrophenyl (DNP) determinant in absolute weight units. The antibodies to be measured are adsorbed quantitatively onto an appropriate immunoadsorbent such as DNP polyacrylamide. The particulate immune complexes are then incubated with a standard dilution of a potent rabbit antiserum to mouse IgG. Removal of the rabbit anti-mouse IgG (RaM) immunoglobulins by the complexes decreases the C fixing ability of the RaM supernatants reacted with C and mouse IgG. The decrements in C fixation are linearly related to the logarithm of the weight of mouse IgG. The decrements in C fixation are linearly related to the logarithm of the weight of mouse IgG anti DNP added to the immunoadsorbent. A calibration curve is constructed with known amounts of mouse IgG )anti-NDP as measured by quantitative precipitation. Concurrent assays with the early mouse anti-DNP sera permit conversion of the losses in C fixing potencies to weight units of mouse IgG anti-DNP by interpolation on the calibration curve.

Animals↗
PubMed1978

Studies on immunosuppression by cobra venom factor. II. On responses to DNP-Ficoll and DNP-Polyacrylamide.

We have reassessed the effects of CVF administration on the humoral responses to two T-independent immunogens: DNP-Ficoll and DNP-Polyacrylamide. With high immunogen doses, little or no evidence of suppression was found. However, when the immunizing dose was reduced, suppression of both IgG and IgM responses became apparent. As indicated in a previous report, the immunosuppressive effect of CVF on T-dependent responses may result not only from C depletion but also from the generation of C cleavage products that may impair the auxiliary contribution of macrophages to the generation of these humoral responses. A similar mechanism may be applicable to the suppression of antibody production to DNP-Ficoll and DNP-PAA in view of recent reports showing a macrophage requirement for the response to these immunogens.

Acrylamides↗
PubMed1978

Studies on immunosuppression by cobra venom factor. III. On early responses to sheep erythrocytes in C5-deficient mice.

CVF administered before immunization can profoundly depress humoral responses in C-sufficient mice. In AKR/JC5- mice given CVF before i.v. immunization with SRBC, only IgG levels were depressed, IgM titers being equivalent to those of untreated controls. The immunosuppressive effect became inapparent when the i.p. route of immunization was adopted. In DBA/2J C5- mice reduction of both IgG and IgM titers was observed irrespective of the route of immunization. The degree of suppression was, however, much more marked when mice were challenged intravenously. Essentially identical results were obtained with C5+ DBA/1J mice. These studies indicate that immunosuppression by CVF is unrelated to activation of the late C components. The significance of these findings is discussed with reference to the possibility that the generation of biologically active C fragments in conjunction with a C3 deficiency may account for immunosuppression by CVF.

Animals↗
PubMed1978

Studies of immunosuppression by cobra venom factor. I. On early IgG and IgM responses to sheep erythrocytes and DNP-protein conjugates.

The immunosuppressive activity of CVF was evaluated in mice immunized with sheep erythrocytes and dinitrophenylated proteins. Serum antibody levels to these immunogens were estimated in activity units and on a weight basis for IgG. IgM as well as IgG antibody responses were diminished in mice pretreated with CVF. However, when soluble immunogens were incorporated in CFA the suppressive effect associated with CVF was inapparent. It is suggested that C depletion per se may not fully account for the observed immunosuppression. The latter may result not only from the depression of C3 levels but also from the biologic activities of C cleavage products some of which modulate the secretory functions and state of activation of macrophages.

Animals↗
PubMed1977

Serum complement changes in W/Fu rats inoculated with syngeneic (C58NT) D lymphoma cells.

Weanling W/Fu rats were inoculated intraperitoneally with 1 X 10(6) to 1 X 10(7) (C58NT)D Gross virus-induced lymphoma cells. Sera obtained 7 days later showed moderate to marked depressions of overall hemolytic activity, C1, C3 and properdin. These changes were not observed in uninjected W/Fu rats or in animals inoculated with syngeneic normal spleen cells. In the latter group and in the tumor-bearing animals, factor B levels were also depressed. Evidence of complement utilization was also observed in the ascitic fluids of the tumor-bearing W/Fu rats.

AKR murine leukemia virus↗
PubMed1976

A properdin system intermediate formed by zymosan and serum at 0 degrees C.

The interaction of guinea pig or rat serum with Z at 0 degrees C leads to the formation of properdin pathway intermediate, ZPI, whose activity is assessed by its capacity to deplete the titer of cobra venom inducible lysis in diluted rat serum. The formation of ZPI does not require C1 or C2 and is not diminished by prior absorption of the serum with Z. In contrast, removal of P suppresses ZPI formation. Both Ca++ and Mg++ are essential cofactors for the formation of this intermediate whose function is abrogated in the presence of anti-C3, anti-P, but not by anti-Factor B. Since C4-deficient guinea pig serum is also effective in ZPI formation, the data suggest that ZPI is an alternative pathway intermediate containing both P and C3.

Animals↗
PubMed1975

The humoral response to DNCB: its detection by different techniques.

Antibodies in the sera of guinea pigs immunized with DNCB were detected by Ouchterlony-type analyses and were estimated in weight units by the mABC procedure. Assays of these sera by means of passive cutaneous anaphylaxis, passive hemolysis, or the ABC-33 antigen-binding technique were essentially negative. The validity of the mABC analyses was established by comparison of results obtained in quantitative precipitation studies with sera of guinea pigs immunized with DNP-BGG. In these instances, also, the ABC-33 assays failed to detect all the anti-DNP immunoglobulins.

Animals↗
PubMed1975

Humoral immunity in rodent malaria. III: Studies on the site of antibody action.

Serum which protects rats against Plasmodium berghei infections fails to sensitize parasitized erythrocytes in vitro for in vivo destruction. Further, the efflux of 86Rb from parasitized erythrocytes in the presence of complement is not accelerated. On administration to animals with preexisting malaria, it does, however, produce a relatively slow decline in parasitemia, a phenomenon interpreted in terms of the gradual production and/or release of reactive antigenic determinants associated with maturation of the parasites. Protective activity is elaborated in the serum of animals during the development of parasitemia, thus creating a situation in which there is apparently the coincident presence of antibody and its putative antigen in the circulation. Little absorption of protective activity by parasitized cells or parasites was observed in vitro. However, in vivo removal of the protective activity during an ongoing infection could be demonstrated. These observations favor the notion that protective antibody exerts its influence not on the bulk of the parasitized erythrocytes, but rather on some subpopulation thereof. The cumulative evidence of this and other studies suggests that the stage(s) involved are the schizonts and/or merozoites.

Absorption↗
PubMed1975

Activation of the alternative (properdin) pathway by divalent cations.

Mg++, Mn++ and Co++ activate the C system as judged by the reduction in cobra venom factor indeed hemolysis, and cleavage of properdin factor B and C3. The maximum effect requires the addition of 5 to 10 mM of these cations to dialyzed sera respond in similar fashion indicating that these divalent cations can trigger the alternative pathway without the addition other activating agents.

Animals↗