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Biomedical subjects

J G Michael

Publications and source records attributed to J G Michael.

At least 73 records · Page 4Linked to original sources
PubMed1980

beta 2-microglobulin in human tumors heterografted into athymic mice.

Beta 2-microglobulin (beta 2m) content of several human tumor lines implanted into athymic mice was investigated. The concentration of this protein was found to vary greatly from tumor to tumor. The growth rate of the tumors was inversely related to the amount of the extractable beta 2m. The fastest growing, undifferentiated tumors contained the least amount of beta 2m.

Animals↗
PubMed1980

Release of beta 2-microglobulin by human tumors grown in nude mice.

Human tumors implanted subcutaneously into athymic mice produced human beta 2-microglobulin which was readily identified and quantified in mouse plasma. Implanted solid tumors of the lines Clouser, SW480, Hep-2, Capan-1, and HT-29 released amounts of beta 2-microglobulin directly related to tumor mass. The extractable beta 2-microglobulin per gram of tumor was constant for each cell line, but there was a 100-fold variation between the lines. In general, the plasma level of beta 2-microglobulin correlated with the amount of free beta 2-microglobulin extracted from each tumor. From these observations it can be concluded that the variablility observed in the circulating levels of beta 2-microglobulin among cancer patients is related to the beta 2-microglobulin content of the tumor and the total tumor mass.

Animals↗
PubMed1979

Influence of the mouse hepatitis virus (MHV) infection on the growth of human tumors in the athymic mouse.

The growth characteristics and histological appearance of tumors resulting from transplantation of the tumor lines HEp-2 and SW480 into pathogen-free and mouse hepatitis virus infected athymic mice were studied. Subcutaneous or intraperitoneal implantation 1 x 10(6) neoplastic cells into pathogen-free animals resulted in tumor growth. Subcutaneous transplants grew locally, surrounded by a capsule of connective tissue. The fibrovascular stroma supporting the neoplastic tissue was minimal and infiltration of tumor capsule was observed. Intraperitoneal tumors grew in a multifocal pattern, were not encapsulated, showed marked invasiveness and metastasized. The same number of neoplastic cells (1 x 10(6)) transplanted into hepatitis-positive animals failed to develop into grossly visible tumors. When the number of transplanted cells was increased to 2 x 10(7), tumors appeared in a few animals. All tumors, regardless of the site of transplantation, were characterized by the presence of severe fibrohistiocytic reaction at the site of implantation that possibily influenced the tumor growth. No evidence supporting T-cell-mediated tumor rejection was observed. It is concluded that the state of health of the athymic mice is critical for the growth of human tumors and may account for the variations in reporting successful transplantation of such tumors in nude mice.

Animals↗
PubMed1979

Immune response to Escherichia coli B surface antigens.

The cell surface antigens of Escherichia coli B were investigated. We found that mice immunized with live bacteria responded with an immune response directed mainly against the protein structure of the cell surface. The lipopolysaccharide component of the bacterium was immunogenic, but its contribution to the overall response was only secondary. It is suggested that when considering the immune response to gram-negative bacteria, more attention should be given to the protein antigens.

Animals↗
PubMed1979

Monitoring the therapy of human tumor xenografts in nude mice by the use of lactate dehydrogenase.

With the use of circulating human lactate dehydrogenase (LDH) as a tumor marker, growth and remission of human tumor lines SW480, HEp-2, and Clouser, implanted into female BALB/c athymic nude mice, were followed during therapy. Three types of therapy were used: X-radiation, cyclophosphamide, and diphtheria toxin. After therapy tumor sizes were measured with calipers and compared to changes in the levels of circulating human LDH. Changes in LDH levels paralleled changes in tumor size, but the enzyme fluctuations were more pronounced. Mice bearing intraperitoneally growing SW480 and HEp-2 tumors were effectively treated with diphtheria toxin, and the measurement of circulating LDH was examined as a parameter for gauging the effectiveness of chemotherapy on tumors that could not be visualized. Circulating human LDH can be used to detect intraperitoneal tumor growth and/or remission and to predict death of the animal due to the tumor.

Animals↗
PubMed1979

Immunoregulatory function of specific IgG. II. Clinical evaluation of combined active and passive immunotherapy.

Based upon previous clinical data suggesting that the potential therapeutic benefits of hyperimmune specific IgG could involve neutralization and regulatory effects, this cooperative study evaluated the efficacy and safety of combined active and passive immunotherapy in previously untreated ragweed-sensitive patients. Symptom scores and indices of patients receiving ragweed-specific globulin plus rush desensitization with ragweed extract were significantly reduced (p less than 0.05), as compared to control patients treated with albumin and active rush immunotherapy. Postseasonal RAST levels were either unchanged or decreased in 28 of 33 patients receiving hyperimmune gamma-globulin. These data were significantly different from those in albumin-treated patients (p less than 0.002). The usual anamnestic rise of ragweed-specific IgE was modified without affecting the ongoing synthesis of ragweed specific IgG. Mild constitutional symptoms were observed in patients undergoing rush immunization, but the overall procedure was relatively well tolerated and no serious or treatment-refractory constitutional problems were encountered. This clinical trial suggests that ragweed immune gamma-globulin might be a useful therapeutic adjunct when administered in close association with optimal amounts of allergen.

Adolescent↗
PubMed1979

Immunological properties of peptic fragments of bovine serum albumin.

The effect of peptic degradation on the immunological and antigenic properties of bovine serum albumin (BSA) was investigated. Molecular fragments obtained after various times of digestion (3-360 min) were studied. Enzymatic digestion resulted in a rapid loss of serologically defined antigenic determinants. The immunogenicity of the fragments as measured by the level of reaginic and total anti-BSA antibody response in BDF1 mice was also diminished. Pre-treatment of mice with fragments exhibiting a low density of B-cell interacting determinants before immunization with BSA, resulted in significant suppression of both the primary and secondary antibody response. The most effective immunosuppressive fragments were obtained following removal of peptides which bound to anti-BSA antibodies. The suppression was shown to be antigen specific. It was concluded that separate determinants on the BSA molecule were responsible for the immunogenic and suppressive properties of the antigen.

Animals↗
PubMed1978

Immunoregulatory function of specific IgG. I. Results in nonatopic subjects.

Nonatopic subjects immunized with short ragweed developed both reaginic IgE and blocking IgG antibodies to the antigen. Administration of 250 microgram-specific ragweed IgG antibodies 1 week before, simultaneously, or up to 2 weeks after start of immunization with ragweed extract abrogated the production of anti-ragweed reaginic antibodies which was measured by skin reactivity. Formation of specific ragweed IgG antibodies was unaffected by IgG treatment. These results indicate selective regulation of an immune response in humans by IgG.

Antibody Formation↗
PubMed1977

Regulation of reaginic antibody production in mice. I. Suppression by antigen of IgE antibody production in vitro.

Regulation of IgE production by antigen in a primed murine splenic lymphocyte culture system was described. Maximum IgE antibody production was found to occur when cells were cultured in the absence of exogenously added antigen. A cells and T lymphocytes did not affect the production of anti-DNP IgE antibody. By using a hapten-carrier antigen system (DNP-EA) for priming mice in vivo, it was found that the production of anti-DNP IgE by spleen cells in vitro was inhibited by hapten when coupled to homologous (EA) or heterologous (BGG) carrier, and was not enhanced or inhibited by homologous carrier. Anti-DNP IgE antibody production by cultures depleted of macrophages or T lymphocytes was found to be as sensitive to the suppressive effects of hapten as was the IgE production by whole spleen cell cultures. Both IgM and IgG secondary anti-DNP PFC responses in vitro were enhanced by the presence of the homologous hapten-carrier or carrier alone. DNP-BGG had no effect on the anti-DNP IgM or IgG PFC responses of the cultures. These data suggest that endogenous production of antibody (IgM or IgG) was not responsible for the observed suppression of the IgE response in vitrol The experimental results presented indicate that the regulation of the IgE production by antigen in the primed mouse splenic lymphocyte cultures was a consequence of the direct interaction of hapten with IgE B cells.

Animals↗
PubMed1977

Isolation and characterization of immunoregulatory factors from normal human serum. I. Preliminary biochemical and biological characterization of immunosuppressive factors.

Normal human serum was shown to inhibit the mitogenic effects of bacterial lipopolysaccharide and Con A on mouse spleen lymphocytes and reduce the in vitro antibody response to SRBC by these cells. Furthermore, it was demonstrated that immune suppression occurred without loss of lymphocyte viability. Fractionation of normal human serum resulted in isolation of several immunoenhancing and immunoinhibitory fractions. Electrophoretic analysis of the immunoinhibitory fractions revealed a complex array of serum proteins. The most prominent proteins on polyacrylamide electrophoresis stained for both proteins and carbohydrate. The heterogeneity of immunoinhibitory fractions were further substantiated by their differential susceptibility to trypsin, periodate, and 2-mercaptoethanol treatment. Heterogeneity of the fractions was also shown to be related to difference in their biologic activity as expressed in their effects on mitogenicity and immunogenicity of LPS in mouse splenic cultures. This study lends evidence to the consideration that normal human serum contains several immunoregulatory factors with differing biochemical characteristics and cellular sites of action.

Animals↗
PubMed1977

Immunosuppressive properties of a peptic fragment of BSA.

The immunogenic properties of a peptic fragment of BSA were investigated. BSA was subjected to limited proteolysis by pepsin and the resulting fragments were separated on DEAE cellulose. The fragment under consideration, Fraction Ia (m.w. 8000 to 10,000), did not precipitate with anti-BSA serum but did inhibi, the binding of specific antibody to labeled BSA, indicating the presence of determinants found on the native antigen. BDF1 mice immunized with Fraction Ia in A1 (OH)3 gel or in complete Freund's adjuvant produced no significant antibody response as measured by passive cutaneous anaphylited a (PCA) or by a modified Farr assay. The fragment elicited a PCA reaction in mouse skin sensitized with anti-BSA serum. Treatment of mice with single doses of Fraction Ia at various time intervals before immunization with BSA resulted in significant suppression of the formation of anti-BSA antibody. The conditions of suppresion of the IgE response by the peptic fragment were studied in greater detail. Evidence is presented that such suppression can be attributed to the presence of specific T suppressor cells in our system.

Animals↗
PubMed1977

Human lactic dehydrogenase as a marker for human tumor cells grown in athymic mice.

Human tumors implanted s.c. into athymic mice released lactic dehydrogenase (LDH) isoenzymes unique to human tissue. These isoenzymes were readily identified and quantitated in mouse plasma. When injected into mice i.p. or i.v., human LDH isoenzymes were rapidly cleared from the blood circulation, decreasing to within 10% of the initial value in 12 hr. When human tumor cell lines (HEp-2 and T-24) were injected i.v. into heterozygote or athymic mice, they released LDH isoenzymes over a 24-hr period. When these cells were injected by the i.p. route, they released the isoenzymes over the 4-day period studied. Solid tumors of HEp-2, T-24, and SW-733 cells s.c. implanted continuously released amounts of LDH that were directly related to tumor mass. Therefore, the measurement of plasma levels of human LDH isoenzymes in athymic mice is a useful parameter for detecting the presence and growth of human tumors in these animals. Since the bulk of the released LDH is assumed to derive from injured or destroyed human tumor cells, the assay for these isoenzymes should provide a useful marker for determining the effectiveness of experimental antitumor therapy in athymic mice.

Animals↗