Biomedical subjects
M M Sigel
Publications and source records attributed to M M Sigel.
Enhanced killer cell activities induced by progressive tumor growth.
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Tumor antigen extracts stimulate cytotoxicity against unrelated target cells.
A new cytotoxicity assay for the study of tumor antigens is described. Splenocytes from normal and mammary-tumor-bearing BALB/c mice were depleted of glass-adherent cells, exposed to various concentrations of tumor extracts and mixed with 51Cr-labelled chick red blood cells. Cytolysis evidenced by 51Cr release was determined 20 h after incubation at 37 degrees C. Lymphocytes from tumor bearers exerted no cytotoxic action per se, but became cytolytic after confrontation with immunogenic tumor extracts. Although this cytotoxicity is expressed against targets other than the cells containing the sensitizing antigen, i.e., a non-specific activity, its induction is strictly specific as evidence by the following: (1) extracts of D1-DMBA-3 tumors exerted an inductive effect only in lymphocytes from mice bearing this tumor and not in lymphocytes from normal mice; and (2) extracts of normal tissues or of a non-immunogenic mammary tumor, D1-DMBA-2, did not induce cytotoxicity in lymphocytes from normal or tumor-bearing mice. This approach may provide a useful method for in vitro determination of cell-mediated immunity in which specific reactions can be induced by tumor extracts as opposed to intact tumor cells.
Emergence of a subpopulation of lymphocytes bearing theta antigen and complement receptor during tumor growth.
Spleens from BALB/c mice transplanted with mammary tumors display a significant increase in the percentage of lymphocytes bearing complement receptors (CRL) while the percentage of cells bearing surface immunoglobulins (SIg) remains unchanged in comparison with that in spleens from normal animals. Upon separation on nylon columns, the increase in CRL in the spleens from tumor-bearing mice was limited to the non-adherent cell population. Simultaneous maker analysis disclosed that these CRL lacked detectable SIg. Indirect immunofluorescence indicated that these cells possessed theta antigen. Absence of SIg and the presence of theta antigen coupled with the restricted occurrence of these cells in the nylon-non-adherent population which responded to PHA and Con A but not to LPS indicate that these cells may constitute a subset of T cells. The paucity of this subpopulation of spleen lymphocytes in normal spleen suggests that their emergence is related to tumor growth.
Migration inhibition and blastogenic reactions with viral and tumor antigens in transplantable mammary tumor systems.
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Macrophage migration inhibition and lymphocyte stimulation with mammary tumor virus associated antigens in Balb/c mice.
Lymphocytes of MTV-negative Balb/c mice are sensitive to one or more antigens of MTV as determined by blastogenic transformation and migration inhibition assays. The lymphocytes from MTV-positive Balb/cfC3H mice are nonresponsive in these assays but become responsive after the mice have been implanted with MTV-positive tumors. The latter findings imply that there may be either a state of tolerance to MTV antigens which is broken by the tumor transplant or that the responses are directed towards antigens to which the host is not tolerant. The cause of the sensitivity of lymphocytes from MTV-negative Balb/c mice to MTV antigens has not been determined but two possible explanations are discussed: horizontal transmission and derepression of genetic information for viral antigen.
In vitro immune responses to viral and tumor antigens in murine breast cancer.
Inhibition of migration of peritoneal exudate cells proved to be a useful measurement of cell-mediated immunity which correlated in several respects with blastogenic transformation reactions. Lectins (phytohemagglutinin and concanavalin A) inhibited the migration of peritoneal exudate cells from normal and tumor-bearing mice, whereas tumor antigen caused inhibition of migration of cells from tumor-bearing animals only. The disparity in immunogenic capacity previously observed with lymphocyte transformation studies was also manifested in migration inhibition, i.e., D1-DMBA-3 tumor being immunogenic and D1-DMBA-2 being nonimmunogenic. Using the migration inhibition and blastogenic transformation reactions, responses were obtained to mammary tumor virus (MTV) antigen(s) in cells from BALB/cCrgl mice, which are free of MTV. In contrast, cells from MTV-positive BALB/cfC3H mice failed to respond to this antigen(s) in both reactions, suggesting a form of tolerance. However, the reactions became positive after implantation with MTV-containing spontaneous mammary tumors. Two possible explanations of the origin of reactive lymphocytes, horizontal transmission, or activation of a gene coding for an MTV antigen(s), are discussed.
Clearance of bacteriophage in poikilothermic vertebrates and the effect of temperature.
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Increase in the proportion of cells with the C'3 receptor in BALB/c mice bearing mammary tumors.
Transplantation of mammary tumors originally induced by dimethylbenzanthracene caused splenomegaly and an increase in the total population of spleen cells paralleling the increase in tumor size. At least part of the hypercellularity was due to in situ proliferation as evidenced by the increased number of blast forms and mitotic figures. The cells were characterized with respect to parameters generally associated with B-cells; surface immunoglobulins as detected by immunofluorescence and C'3 receptors as determined by rosette formation with sheep red blood cells (SRBC) coated with rabbit anti-SRBC and mouse complement. There was no change in the percentage of B-cells with surface immunoglobulin in tumor-bearing mice compared with the control animals. However, there was a profound change in the representation of cells bearing C'3 receptors. The percentage of the cells increased dramatically with tumor growth. Various possibilities regarding the nature and function of these cells are considered.
Letter: Cerebral metastases and carcinoembryonic antigen in CSF.
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Characterization of a conditional mutant of Rouse sarcoma virus with alterations in early and late functions of cell transformation.
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Ecteinascidia turbinata extracts inhibit DNA synthesis in lymphocytes after mitogenic stimulation by lectins.
Aqueous ethanol extract of a tunicate which was previously found to exert antitumor and immunosuppressive activities in vivo was tested for its effect on normal human lymphocytes in vitro. The extract suppressed the uptake of tritiated thymidine by lymphocytes stimulated with mitogen. This suppressive effect did not require continuous presence of the extract. Treatment of lymphocytes prior to mitogenic stimulation resulted in suppressive effect. The fact that suppression by the extract could also be achieved 24 hr after exposure to mitogen, an interval which was found to suffice for the attainment of maximal commitment for blastogenic transformation indicates that Ete can act at a stage subsequent to the binding of the lectin and elicitation of a mitogenic signal(s).
Urinary bladder carcinogenesis in the dog: preliminary studies on cellular immunity.
The immunologic status of dogs undergoing bladder carcinogenesis with 4-amino-biphenyl and normal littermate controls is being evaluated. Studies using blastogenic transformation, nonimmune cytotoxic reactions, and rosette formation have revealed that dogs possess lymphocytes that have some properties similar to those of B and T cells of other species. Since tumors are now just appearing and hence are not yet available for specific immunologic determinations, the assessments had to be limited for the present to other types of antigens and mitogens (yeast, red blood cells and plant lectins). No major changes in reactions of cells from the carcinogenized animals have yet been observed during the preneoplastic phase as measured by phagocytosis, migration inhibition, or cytotoxicity tests, although a trend to lower blastogenic responses was noted. It yet remains to be seen whether lower lymphocyte responses to mitogens in carcinogenized dogs are of prognostic value for the early detection of tumors of the bladder.
Correlation of tumor growth and cell-mediated immune responses of mice bearing mammary tumors following surgical procedures.
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A differential effect of IgM and IgG antibodies on the blastogenic response of lymphocytes to rubella virus.
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Lymphocyte response to mammary tumor antigens free of mammary tumor virus in relation to clinical status.
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Primitive immunoglobulins and other proteins with binding functions in the shark.
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In vitro methods to complement in vivo approaches utilizing combinations of chemotherapy and immunotherapy.
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