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Biomedical subjects

J T Forbes

Publications and source records attributed to J T Forbes.

30 records · Page 2Linked to original sources
PubMed1981

The unrecognized extragonadal germ cell cancer syndrome.

Within 3 years we saw 12 patients diagnosed initially as having poorly differentiated or undifferentiated carcinomas who, we believe, actually had extragonadal germinal cancers. Serum levels of the beta subunit of human chorionic gonadotropin (beta-HCG) or alpha-fetoprotein were useful in suggesting and supporting the diagnosis: Levels of one or the other were elevated in six of 10 patients in whom they were measured but levels of both, in only one patient. Staining of histologic specimens for beta-HCG or alpha-fetoprotein showed intracellular localization of one of these markers in the cancer cells of all four patients studied. All patients responded to therapy (11 treated with chemotherapy with or without radiotherapy, one with excision and radiotherapy only), with complete remissions in seven of 12. Two of the patients who had a complete remission have experienced relapse, and five have continued in disease-free remission from more than 8 to more than 56 months. Histologically atypical extragonadal germ cell neoplasms may be commoner than previously supposed. Physicians should consider this treatable and potentially curable cancer in selected patients having poorly differentiated or undifferentiated carcinomas.

Adult↗
PubMed1980

Human granulocyte-specific nuclear antigen(s). II. Detection of antigens in human proliferative syndromes.

Antisera raised to dehistonized chromatin from isolated normal human granulocytes revealed the presence of chromatin-associated antigens specific for the human neutrophils that appear during late stages of myeloid cellular differentiation. Immunological specificity was demonstrated by C fixation, immunodiffusion, and immunocytochemical reactions. Chromatin prepared from both normal granulocytes and specimens of myeloid leukemia showed immunologic reactivity. Although the normal antigens were detected in a specimen of CML, the position of immunodiffusion precipitin lines was different from that obtained with normal granulocyte chromatin. In addition, chromatin prepared from the myeloid leukemic cell line HL-60 expressed only one of the three precipitin bands normally found in immunodiffusion. The immunocytochemical staining reaction was confined to the nucleus of mature neutrophils in normal peripheral blood smears. Greater than 90% of cells in peripheral blood specimens of CML showed positive immunocytochemical nuclear staining. In other types of leukaemia, the normal mature granulocyte reacted with antiserum, but the nonmyeloid leukemic cells in these specimens did not. The specificity of immunologic reactions described here suggests the usefulness of nuclear antigens as cell markers.

Animals↗
PubMed1977

Soluble tumor antigen-induced lymphocyte proliferation: effects of serum from normal and tumor-bearing mice.

The effect of serum from mice bearing methylcholanthrene-induced fibrosarcomas on the lympho-proliferative responses of their spleen and lymph-node cells to 3 M KCl-solubilized tumor antigens has been investigated. Low concentrations of serum (less than or equal to 2.5%) collected throughout the course of tumor growth were inhibitory. Normal sera collected from age-matched control mice were often slightly inhibitory, but to a significantly lesser extent at identical serum concentrations. The inhibitory effect of tumor-bearing serum was not limited to homologous tumors, but was also observed when cross-reacting syngeneic tumor antigens or serum from animals bearing other syngeneic tumors were added to the assay mixture. At the low concentrations used, tumor-bearing sera inhibited only tumor-antigen-induced proliferation, and not proliferation induced by T cell mitogens. The inhibitory effects of tumor-bearing sera on lympho-proliferative responses to soluble tumor antigens appear to be similar to the inhibition seen as "serum blocking" in other assays of tumor immunity.

Animals↗
PubMed1976

Ability of delayed-type hypersensitivity reactions to distinguish tumor-associated antigens and histocompatibility antigens in soluble extracts from murine fibrosarcomas.

The footpad swelling (FPS) test for delayed-type hypersensitivity in the mouse was evaluated for its ability to measure both tumor-associated antigens (TAA) and histocompatibility (H) antigens solubilized from methylcholanthrene (MCA) induced fibrosarcomas of C57B1/6 (B6) mice. Tests for TAA were performed in mice immune to syngeneic tumors while H-antigens were assayed in mice immunized with skin allografts. FPS was most intense in B6 mice challenged with TAA from the immunizing B6 tumor, but also occurred in response to cross-reactive TAA solubilized from another B6 fibrosarcoma. Tests for tumor-associated H-antigens in allograft immune mice were strongly positive in response to donor/recipient H-antigen differences and proved sensitive to shared third-party H-antigen differences. Comparison of soluble antigens from the same tumor maintained in vitro and in vivo revealed that, while both TAA and H-antigens could be detected in preparations from the in vivo tumor line, only TAA and not H-antigens could be detected by RPS in extracts prepared from the in vitro tumor line. These experiments have demonstrated that the mouse FPS test can distinguish both TAA and H-antigen specificities persent in the same complex mixture of tumor-cell antigens.

Animals↗
PubMed1976

Specific antigen stimulated lymphocyte proliferation in osteosarcoma.

A lymphocyte proliferation assay (LPA) for cellular immune responses to osteosarcoma antigens is described and applied to an examination of peripheral blood lymphocytes (PBL) taken from osteosarcoma patients. The antigen preparations were derived from 3 M KC1 solubilized osteosarcoma, taken from a limited number of patients. Lymphocytes from most tumor-bearing patients were stimulated to significant proliferation when cultured in normal human serum. Such stimulation was observed whether or not the lymphoid cells were preincubated 24 hours at 37 degrees C prior to addition of antigen. Patients whose lesion had been resected and who were without evidence of disease for 5-70 months had diminished proliferative responses. Lymphocytes from normal subjects, from patients having other types of sarcoma, and patients having carcinomas rarely responded to the soluble osteosarcoma antigens. When responsive PBL taken from tumor-bearing patients were cultured in autologous serum, the proliferative responses were abrogated or blocked. Serial assays made in the course of bearing this tumor under a variety of therapeutic regimens, including an immunotherapy protocol, suggest that the LPA may be useful in monitoring clinical progress of the disease and possibly in other immunotherapy protocols for osteosarcoma.

Antigens, Neoplasm↗
PubMed1975

T mitogens trigger LPS responsiveness in mouse thymus cells.

Mouse thymus cells are essentially unresponsive to lipopolysaccharide (LPS) stimulation. However, when cultured with minimally mitogenic levels of concanavalin A or submitogenic ratios of mitomycin-treated allogeneic spleen cells, in combination with LPS, they demonstrate levels of DNA synthesis de novo or greater than those induced by the T cell mitogen alone. Dose-response kinetics were characteristic of LPS. The subpopulation containing the LPS responsive cells was of low net buoyant density. Neither phytohemagglutinin nor pokeweed mitogen acted synergistically with LPS in this model to trigger thymus cells. The data suggest that LPS triggering may involve interaction with a T cell subpopulation.

Animals↗