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Biomedical subjects

G M Edelman

Publications and source records attributed to G M Edelman.

At least 271 records · Page 15Linked to original sources
PubMed1977

Role of surface modulating assemblies in growth control of normal and transformed fibroblasts.

Cellular microtubules, microfilaments, and surface receptors have been postulated to form a surface modulating assembly that regulates surface receptor mobility and cell growth. To test this hypothesis, we examined three agents known to affect cell growth [colchicine, concanavalin A (Con A), and the src gene product of Rous sarcoma virus] for their effects on chick embryo fibroblasts. Individual cells from serum-starved normal fibroblast populations became committed to enter S phase at various times over a 12 hr period after exposure to serum. Colchicine and other microtubule-disrupting agents blocked entry into S phase at a point close to the commitment point for each cell. The lectin Con A also blocked entry into the S phase when present in doses sufficient to modulate surface receptor mobility. In contrast, succinyl-Con A, which does not induce surface modulation, had no effect. Both Con A and colchicine blocked the appearance of cytoplasmic factors capable of stimulating DNA replication in a cell-free system. To study endogenous effects on the surface modulating assembly, we infected fibroblasts with a Rous sarcoma virus (tsNY68) having a temperature-sensitive mutation in the transforming (src) gene. We have previously shown that microtubular and microfilamentous structures of the surface modulating assembly are direct or indirect targets of the src gene product with consequent reduction in the capacity of Con A to induce surface modulation. TsNY68-infected fibroblasts shifted to the non-permissive temperature acquired normal microtubular morphology more rapidly (2 hr) than cells grown at the permissive temperature in the presence of protein synthesis inhibitors (7.5 hr). This suggests that the src gene product acts directly on the surface modulating assembly rather than via the nucleus or at the level of protein synthesis. Furthermore, "transformation" of the surface modulating assembly was partly blocked by treatment of the infected cells with Con A but not succinyl-Con A. Both Con A and colchicine inhibited entry into the S phase following a shift from nonpermissive to permissive growth conditions. All of these observations are in accord with the hypothesis that the surface modulating assembly acts as a signal regulator in growth control.

Animals↗
PubMed1977

Receptor diffusion on cell surfaces modulated by locally bound concanavalin A.

In order to test the anchorage modulation hypothesis, the fluorescence photobleaching recovery method was used to measure the global inhibition of cell surface receptor mobility induced in 3T3 mouse fibroblasts by local binding of platelets labeled with concanavalin A (Con A). By measuring the diffusion of antibody-labeled cell surface receptors at various points on the cell surface, two states, immobile and mobile, were distinguished in the receptor population. Bound Con A-platelets, occupying between 4% and 30% of the cell surface, decreased the diffusion coefficient of the mobile population by a factor of 6. The magnitude of this effect was independent of distance from the sites of the bound Con A-platelets, demonstrating the propagated and nonlocal properties of the modulation effect. The immobile fraction of the population was not changed by Con A-platelet binding. Modulation of the diffusion constant of mobile receptors was partially reversed by treatment with microtubule-disrupting agents such as Colcemid and Vinca alkaloids. High doses of soluble Con A induced even higher levels of modulation than Con A-platelets, but reversal by microtubule-disrupting drugs was observed. These experiments provide additional support for the anchorage modulation hypothesis and provide a measure of the nature and degree of mobility at the molecular level. They also put important constraints on the hypothesized interactions among submembranous components (microtubules and microfilaments) of surface modulating assemblies.

Antigen-Antibody Complex↗
PubMed1977

Crystallographic studies of bovine beta2-microglobulin.

Crystals of the bovine milk protein lactollin yield x-ray diffraction data extending to a resolution of 2.8 A. Lactollin is a bovine analogue of beta2-microglobulin, a protein that is homologous in amino acid sequence to the constant domains of immunoglobulins and is the light chain of the human and murine major histocompatability antigens. The protein crystallizes in the orthorhombic space group P2(1)2(1)2(1) with a = 77.4, b = 47.9, and c = 34.3 A. The unit cell parameters and physical chemical solution studies indicate that the molecule exists in the crystal and in solution as a single polypeptide chain of 12,000 daltons.

Amino Acid Sequence↗
PubMed1977

Adhesion among neural cells of the chick embryo.

Cell-cell binding of both retinal and brain cells of the chick embryo varied as a function of developmental age, brain cells acquiring their binding properties at an earlier time than retinal cells. Brain and retinal cells of the appropriate age bound as well to each other as to themselves. Antibodies prepared against a molecule released by retinal cells in culture were able to inhibit cell-cell binding between homologous and heterologous pairs of retinal and brain cells. These results suggest that the molecular mechanism of cell-cell binding is the same in these 2 tissues. Analysis of cell surface proteins precipitated by these antibodies suggest that one of the molecules involved in adhesion has a molecular weight of 150,000, and may be derived from a larger precursor. The possible mechanisms of cell-cell binding are discussed in terms of the properties of this molecule.

Animals↗
PubMed1976

Analysis of the stimulation-inhibition paradox exhibited by lymphocytes exposed to concanavalin A.

High doses of Concanavalin A (Con A), which normally inhibit T-lymphocyte stimulation as measured by increases in DNA synthesis, cause these lymphocytes to become committed to mitogenesis while also generating a dominant but reversible negative growth signal. The observed response to the stimulatory signal as measured by the rate of commitment to enter the S phase (i.e., the rate at which the stimulation becomes lectin independent) increases with lectin concentration even in the inhibitory range. The generation of this positive signal is prevented by treating the cells with colchicine. Cells that have become committed but are also simultaneously blocked from entering the S phase by the high doses of Con A can begin synthesizing DNA if the lectin is released by adding a competitive inhibitor of binding. Experiments done in agarose cultures in which lymphocytes are kept from contact with each other suggest that the reversible inhibitory signal is mediated by structures in the individual cells rather than as a result of agglutination. Continuously dividing cells of the lymphoid line P388 are also individually and reversibly inhibited by Con A. These findings are considered in terms of the relation of the inhibitory signal to the microtubular components of cell surface modulating assemblies made up of submembranous arrays of microtubules, microfilaments, and associated proteins.

Cell Aggregation↗
PubMed1976

Formation of hybrid concanavalin A molecules by subunit exchange.

Mixing of native concanavalin A (Con A) and its dimeric succinylated derivative (succinyl-Con A) in glycine-HCl buffer, pH 4.5, resulted in the formation of a new chemical species that could be separated as a unique fraction by DEAE-cellulose chromatography or by gel electrophoresis. The molecular weight of this new component, which contained the subunits (Mr= 26,000) of native Con A and its succinyl derivative in equimolar amounts, was 50,000 at both pH 5 and pH 7. These data suggest that subunit exchange between 2 chemically distinct Con A molecules yields a hybrid molecule consisting of one protomer of native Con A and one protomer of succinyl-Con A. Similar exchange reactions and hybrid molecules were also observed after mixing acetyl-Con A and succinyl-Con A. These procedures provide several new chemical variants of the Con A molecule that may be useful for the analysis of lectin-cell surface interactions.

Binding Sites↗
PubMed1976

Variation and control of specific antigen-binding cell populations in individual fetal mice.

To determine the extent and nature of individual variation in the development of specific antigen-binding cells, the numbers of cells specific for each of two antigens in the spleens of individual random-bred Swiss-L and inbred CBA/J and BALB/c fetal mice were measured as a function of spleen size. For Swiss-L fetuses, the ratio of antigen-binding cells to nucleateated cells varied more than would arise from sampling fluctuation. For each inbred strain, however, the number of cells specific for a given antigen was a constant proportion of the total number of nucleated cells within sampling error. These proportions varied from antigen to antigen, and from strain to strain. The ratio of the proportions of cells specific for the two antigens, however, differed no more from CBA/J to BALB/c mice than would be expected in repeated samples of cells from the spleen of a single fetus. These results confirm at the level of the individual fetus the uniform pattern of development seen for populations of fetuses. They reveal a surprising precision in the proliferation of specific antigen-binding cell populations and suggest that the development of these cells may be subject to strong genetic controls.

Animals↗
PubMed1976

Participation of the H-2 antigens of tumor cells in their lysis by syngeneic T cells.

Cytotoxic T lymphocytes were generated in vitro against H-2 compatible or syngeneic tumor cells. In vitro cytotoxic activity was inhibited by specific anti-H2 sera, suggesting that H-2 antigens are involved in cell lysis. Two observations directly demonstrated the participation of the H-2 antigens on the tumor cells in their lysis by H-2-compatible T cells. First, coating of the H-2 antigens on the target tumor cell reduced the number of cells lysed on subsequent exposure to cytotoxic T cells. Second, when cytotoxic T cells were activated against an H-2 compatible tumor and assayed against an H-2-incompatible tumor, anti-H-2 serum that could bind to the target cell, but not to the cytotoxic lymphocyte, inhibited lysis. H-2 antigens were also shown to be present on the cytotoxic lymphocytes. Specific antisera reacting with these H-2 antigens, but not those of the target cell, failed to inhibit lysis when small numbers of effector cells were assayed against H-2-incompatible target cells or when effector cells of F1-hybrid origin and bearing two H-2 haplotypes were assayed against a tumor cell of one of the parental strains. These findings suggest that it is the H-2 antigens on the tumor cell and not those on the cytotoxic lymphocytes that are important in cell-mediated lysis of H-2-compatible tumor cells.

Animals↗
PubMed1976

Lymphocyte activation by monovalent fragments of antibodies reactive with cell surface carbohydrates.

Antibodies reactive with cell surface carbohydrates were isolated from normal chicken serum and were found to be mitogenic for mouse splenic lymphocytes as assayed by both blast transformation and [3H]thymidine incorporation. The Fab' fragments of these carbohydrate-binding immunoglobulins were just as mitogenic as the divalent native antibody. Moreover, succinylated Fab' fragments, which probably would not form self-associating aggregates, showed similar mitogenic properties. All of these results indicate that, at least for saccharide-specific ligands, multipoint attachment and receptor cross-linkage on the cell to which the ligand is attached may not be a stringent requirement for activation.

Animals↗