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Biomedical subjects

J G Michael

Publications and source records attributed to J G Michael.

At least 55 records · Page 3Linked to original sources

Expression of normal and tumor-associated antigens in human breast carcinoma.

The expression of six cytoplasmic/membrane antigens (beta 2-microglobulin, HLA, HLA-DR, carcinoembryonic antigen, and two breast tumor-associated antigens (TAAs), B6.2 and B72.3) was investigated in serial sections of 28 human breast carcinomas using monoclonal antibodies and the avidin-biotin complex immunoperoxidase technique. The frequency of expression and linkage between these antigens was determined, and antigenic expression was related to patient age, morphologic differentiation, cytologic grade, and estrogen receptor/progesterone receptor content of the tumor. The expression of beta 2-microglobulin and HLA correlated with morphologic differentiation, well-differentiated and moderately well-differentiated tumors expressing these antigens more often than poorly differentiated tumors. Expression of the TAAs, however, was not related to differentiation. There was no linkage between beta 2-microglobulin/HLA and the TAAs. Carcinoembryonic antigen was found to be linked to the TAA, B6.2. Expression of the TAA, B72.3, correlated with patient age. Eighty percent (23 of 28) of the tumors were positive for carcinoembryonic antigen or at least one of the TAAs. The estrogen receptor/progesterone receptor status of the tumor was not statistically related to the expression of any of the antigens studied. Analysis of tumor antigen profiles may provide important information relevant to prognosis, therapy, and early detection of cancer, as well as insights into the nature of the neoplastic process.

Adult↗

Immunoregulation of the anti-bovine serum albumin response by polyclonal and monoclonal antibodies.

Monoclonal or polyclonal antibodies directed toward determinants on limited structures of bovine serum albumin (BSA) (P505-582) were shown to regulate the entire anti-bovine serum albumin (BSA) immune response when passively administered to mice 24 hr prior to immunization. Regulation was observed as suppression of the humoral IgG immune response toward all BSA determinants except those on fragment P505-582. By Day 21 suppression of humoral response was most pronounced toward determinants present on the carboxy terminal end of the molecule (N 307-582). These observations demonstrate that monoclonal antibodies directed against a single determinant on a protein molecule have the capacity to regulate the immune response to a multiplicity of determinants present on the same protein. The data lend support to concepts of antibody-induced regulation by induction of suppressor cells or idiotype recognition.

Animals↗

Immunoregulatory properties of antigenic fragments from bovine serum albumin.

Regulation of the immune response to bovine serum albumin (BSA) by defined substructures of the protein was investigated. The fragments consisted of 41 to 307 amino acids each bearing unique serologic determinants. When administered intravenously the fragments were capable of suppressing the immune response to the entire BSA molecule. The suppression was T-cell mediated and affected the determinants that were linked. The fragments also primed for a secondary anti-BSA response when given in adjuvant; however, the ability to prime was restricted to determinants on the immunizing fragment. The data demonstrate that immune responses to a large protein molecule can be regulated by a relatively small component of its structure and that the ability of a fragment to induce help is more restricted than is its suppressive potential.

Amino Acids↗

Enhancement of antigen-specific suppression by muramyl dipeptide.

The effect of the synthetic adjuvant MDP (N-acetyl-muramyl-L-alanyl-D-isoglu-tamine) on the generation of antigen-specific suppression was investigated. Suppression of the anti-bovine serum albumin response, which was achieved by intravenous administration of a peptic fragment of the antigen, was greatly enhanced by simultaneous administration of MDP. Induction of suppression by a combination of bovine serum albumin fragments and MDP was found to be antigen specific and appeared to occur via the generation of antigen-specific suppressor T cells.

Acetylmuramyl-Alanyl-Isoglutamine↗

Induction of oral tolerance in mice unresponsive to bacterial lipopolysaccharide.

C3H/HeJ lipopolysaccharide (LPS)-unresponsive and closely related C3H/HeSn LPS-responsive mice were rendered tolerant to hen albumin by antigen feeding before parenteral immunization. Both single and multiple feedings of antigen were effective in inducing tolerance to hen albumin in LPS-responsive and -unresponsive strains of mice. Our data demonstrate that ability to respond to LPS is not a prerequisite for induction of oral tolerance to a soluble protein antigen.

Albumins↗

Evaluation of the peroxidase-antiperoxidase method for demonstrating cell membrane B2-microglobulin.

The peroxidase-antiperoxidase (PAP) immunohistochemical technic was evaluated for its usefulness in studying B2-microglobulin (B2m) expression in the cell membrane of human tumor lines grown in athymic mice. Eleven human tumor xenograft lines expressing various amounts of B2m were used. B2m was assessed by three methods: PAP technic on formalin-fixed, paraffin-embedded tissue; indirect immunofluorescence on frozen sections; and radioimmunoassay on soluble tumor extracts. The three technics gave comparable results, and the PAP technic proved to be useful in evaluating B2m.

Animals↗

Development of protective immunity against bacterial and viral infections in tumor-bearing mice coincident with suppression of tumor immunity.

This report addresses the question whether Meth A (methylcholanthrene-induced fibrosarcoma) tumor bearing Balb/c mice are able to develop specific antimicrobial immunity. Although specific suppressor T lymphocytes appeared during tumor growth which prevented expression of antitumor immunity, the development of protective immunity to L monocytogenes, S. pneumoniae or ectromelia virus infections was unimpaired. The Meth A tumor produced a soluble immunosuppressive factor which inhibited lymphocyte and macrophage functions in vitro. Tumor growth failed to inhibit the formation of immunoglobulin essential to antipneumococcal immunity, or the development of a specific acquired cellular resistance of primary importance in immunity to listeria and ectromelia virus infections. That tumor growth did not interfere with the development of cell mediated immunity was demonstrated by the effective transfer of antilisteria immunity by immune spleen from tumor-bearing mice.

Animals↗

Regulation of the immune response to bacterial lipopolysaccharide by adherent cells.

Immune response to bacterial lipopolysaccharide is usually short lived, but it often reappears without additional stimulus in a cyclic fashion. Activated adherent cells, presumably macrophages, were found to have a role in the reduction of the immune response to Escherichia coli O127 lipopolysaccharide. The suppressive activity of the adherent cells was abrogated before renewal of the responsiveness.

Animals↗

Immune response to parental and rough mutant strains of Salmonella minnesota.

Specificity of immune response to smooth and rough mutant strains of Salmonella minnesota was investigated. Immunization of mice with Rd and Re rough mutants resulted in formation of bactericidal plaque-forming cells directed against the lipopolysaccharide structure of both the mutants and the parental smooth strain. These antibody plaques, however, were not bactericidal for smooth strains of other gram-negative species, i.e., Escherichia coli, Salmonella typhosa, Klebsiella pneumoniae, Shigella dysenteriae, and Pseudomonas aeruginosa. Plaques produced against the smooth strain of S. minnesota or other species were not bactericidal for rough strains. It was concluded that immunization with rough mutants produces bactericidal antibodies directed against the closely related parental strain but not against smooth strains of unrelated bacterial species. The relevance of these observations to the nonspecific protection by rough mutants is discussed.

Animals↗

Heterogeneity of beta 2-microglobulin in human breast carcinoma.

beta 2-microglobulin (beta 2m) content and distribution in human benign and malignant breast tissues have been investigated by immunohistologic means, and wide differences in the expression of this protein have been observed. The distribution of beta 2m as determined by indirect immunofluorescence was uniform throughout normal human and benign breast tumor tissues, as well as in human tumor xenografts grown in athymic mice, but marked difference in beta 2m content was demonstrated between individual tumors. In breast carcinomas, heterogeneity in beta 2m expression was found to exist within individual tumors. This heterogeneity was evident mainly in moderately well-differentiated tumors; the majority of poorly differentiated tumors did not express beta 2m at all. It is suggested that the expression of surface beta 2m is an indicator of tumor cell differentiation or maturation.

Animals↗