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Biomedical subjects

R E Cone

Publications and source records attributed to R E Cone.

107 records · Page 6Linked to original sources
PubMed1972

Isolation and partial characterization of lymphocyte surface immunoglobulins.

Immunoglobulins were isolated from the surfaces of lymphocytes from a variety of lymphocyte populations including murine and human thymus lymphocytes and murine spleen and thoracic duct lymphocytes. Cell surface proteins were labeled with iodide-(125)I by lactoperoxidase-catalyzed iodination, and recovered in solution either by solubilization in dissociating solvents or active metabolic release. Immunoglobulins were identified and isolated by immunological coprecipitation. The polypeptide chain structure of immunoglobulins isolated from lymphocyte surfaces was analyzed by polyacrylamide gel electrophoresis of reduced, alkylated samples in acid urea. Human and murine thymus lymphocytes possessed only IgM immunoglobulin on their surfaces. This protein contained light chains and micro-type heavy chains and was characterized by a molecular weight of approximately 200,000. Murine splenic lymphocytes from CBA x C57 animals and congenitally athymic (nu/nu) mice possessed both IgM and IgG on their surfaces. The ratio of micro-chain to gamma-chain was about 3/1. The presence of IgM on thymus lymphocytes probably does not reflect trace contamination by B lymphocytes because comparable quantities of IgM were isolated from both cell populations. Metabolic turnover data suggest that this immunoglobulin is synthesized by the cell population studied. These results provide direct evidence for the presence of immunoglobulins composed of light and heavy polypeptide chains on the surfaces of lymphocytes of all classes.

Animals↗
PubMed1972

Antigen-binding specificity of isolated cell-surface immunoglobulin from thymus cells activated to histocompatibility antigens.

Lactoperoxidase-catalyzed radioiodination of cell-surface proteins was used in the isolation of cell-surface immunoglobulin from thymus-derived thoracic duct lymphocytes activated to histocompatibility-2 antigens. Immunoglobulin was identified by specific precipitation with antiserum to mouse immunoglobulin. Polyacrylamide gel electrophoresis of reduced and alkylated precipitates showed that the immunoglobulin molecules possessed mu-type heavy chains and light chains. Cell-surface immunoglobulin isolated from thymus-derived cells activated to histocompatibility-2 antigens possessed binding specificity for the activating antigens.

Alkylation↗
PubMed1971

Lymphocyte membrane dynamics. Metabolic release of cell surface proteins.

Cell surface proteins of normal and neoplastic lymphocytes were labeled with iodide-(125)I by lactoperoxidase-catalyzed iodination. Incubation of (125)I-labeled iodide cells in vitro resulted in the release of iodinated surface proteins at a rapid rate which was dependent on cellular respiration and protein synthesis. Comparisons by disc electrophoresis showed a marked similarity between urea-soluble surface proteins extracted from iodinated cells and iodinated material released by the cells during in vitro incubation. The rate of release of cell surface proteins from thymus cells was three times faster than that of spleen cells or bone marrow-derived thoracic duct lymphocytes. In addition, different proteins were released at different rates as evidenced by the rate of release of (125)I of rabbit anti-mouse immunoglobulin specifically bound to mouse spleen cells and comparisons by disc electrophoresis of urea-soluble iodinated surface proteins extracted from cells before and after incubation. The results suggest that a dynamic state exists at the cell surface. The possible role of the release of cell surface proteins in cell regulation and communication is discussed.

Amides↗
PubMed1971

Regulation of the immune system by synthetic polynucleotides. 3. Action on antigen-reactive cells of thymic origin.

Polyadenylic-polyuridylic acid complexes, a potent adjuvant to the immune response, were tested for action on thymic-influenced and bone marrow-derived lymphocytes in model systems deficient in one or the other of these cells. Adult mice, thymectomized at birth or mice treated with heterologous antithymocyte serum produced 90-95% fewer splenic rosette-forming cells than normal mice in response to an injection of sheep erythrocytes. Intravenous injection of complexes of homoribopolynucleotides, polyadenylic and polyuridylic acids, poly A:U with SRBC restored immunologic competence to NTx- or ATS-treated mice such that they produced normal or near normal levels of splenic RFC. In addition, injection of poly A:U enabled NTx mice to reject allogeneic skin grafts at the same rate as control mice with an intact thymus. Further reduction in residual thymocytes by combining neonatal thymectomy with ATS treatment reduced the number of anti-SRBC RFC induced by poly A:U. Lethally irradiated mice which received SRBC, excess bone marrow cells, and as few as 40,000 thymic lymphocytes were stimulated by poly A:U to produce RFC. No adjuvant effect was observed when irradiated mice received excess thymic lymphocytes and low doses of bone marrow cells with poly A:U. The results suggested that the adjuvant action of poly A:U was exerted on the thymic-influenced, antigen-reactive cell and that restoration of immunocompetence to NTx- or ATS-treated mice was caused by amplification of a small number of residual antigen-reactive cells which were influenced by the thymus in utero before thymectomy, or which survived treatment with ATS.

Adenine Nucleotides↗
PubMed1971

Enzymic iodination. A probe for accessible surface proteins of normal and neoplastic lymphocytes.

1. Radioactive iodide was covalently bound to living cells from normal mouse spleen and a variety of lymphoid tumours by a system consisting of lactoperoxidase, hydrogen peroxide and iodide. 2. About 3x10(5)-6x10(5) molecules of [(125)I]iodide/cell could be incorporated without affecting cell viability. 3. Electron-micrographic radioautography showed that the radioactive label was associated with the outer surfaces of the cells. 4. Radioiodinated proteins were solubilized in 9m-urea-0.2m-mercaptoethanol and analysed by gel-filtration and disc electrophoresis. 5. Comparison of distinct tumour lines by disc electrophoresis showed qualitative and quantitative differences in protein distribution patterns.

Animals↗
PubMedDate not supplied

Immunological and in-vivo neurological studies on a benzoic acid-specific T cell-derived antigen-binding molecule from the serum of a toluene-sensitive patient.

T-cell-derived antigen-binding molecules (TABMs) specific for benzoic acid were isolated from the serum of a toluene-sensitive patient. The resulting purified TABMs (BA-TABMs) did not contain immunoglobulin G and were associated with the cytokine transforming growth factor-beta (TGF-beta). BA-TABMs bound to benzoic acid conjugated to human serum albumin (BA-HSA), as well as to other chemicals conjugated to human serum albumin-including dinitrophenol and oxazolone. The binding of BA-TABMs to the conjugated chemicals increased the level of detectable TGF-beta, and a similar effect was observed with the unconjugated chemicals, benzoic acid and 2,4-dinitrophenol glycine. The increase in TGF-beta was critically dependent on the ratio between BA-TABMs and the conjugated or unconjugated chemicals; the increase was optimum at intermediate concentrations and absent at low and high concentrations. The authors used an established animal model in vivo and demonstrated that TGF-beta enhanced the inflammatory response induced by the release of neuropeptides from sensory nerves; this enhancement occurred in a dose-dependent manner. The BA-TABMs also enhanced this neurogenic inflammatory response in a dose-dependent manner, and this effect was blocked by anti-TGF-beta antibody. When the authors added either BA-HSA or benzoic acid, the effect of BA-TABMs on neurogenic inflammation was further enhanced at intermediate concentrations of antigen and was unaltered or reduced at higher concentrations. TABMs specific to particular chemicals, as a result of their association with cytokines (e.g., TGF-beta), may be implicated in symptom production in chemically sensitive patients.

Adult↗
PubMedDate not supplied

Clinical and immunological responses in subjects sensitive to solvents.

Twenty patients proved sensitive to a 15-min exposure to 15 ppm toluene. We assessed patients neuropsychologically before and after toluene exposure, and they had impaired cognitive functioning characterized by a deterioration in short- and long-term memory and psychomotor coordination. We measured total immunoglobin G and T-cell antigen-binding molecules against an antigen prepared by conjugation of para-aminobenzoic acid to human serum albumin in 20 patients and 16 controls. There was no significant difference in the immunoglobulin G levels to the antigen in the 2 groups, but the levels of T-cell antigen-binding molecules against the para-aminobenzoic acid conjugated to human serum albumin were elevated significantly in subjects sensitive to toluene. We also found significant associations between T-cell antigen-binding molecule levels and (a) decreased performance on the STROOP (Colour Word) test, (b) a shift in focal length following toluene exposure, (c) clinical assessment of disability, and (d) longer histories of chemical exposure. The measurement of T-cell antigen-binding molecules against chemical haptens may be valuable in the assessment of patients who are sensitive to chemicals.

Adult↗