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Biomedical subjects

D Gospodarowicz

Publications and source records attributed to D Gospodarowicz.

At least 217 records · Page 12Linked to original sources
PubMed1975

Purification of a fibroblast growth factor from bovine pituitary.

The purification from bovine pituitary gland of a growth factor responsible for the control of animal cell division in tissue culture is reported. This growth factor is a polypeptide of 13,300 molecular weight and is homogeneous when analyzed by polyacrylamide gel electrophoresis, carboxymethyl-Sephadex gradient elution chromatography, and Sephadex G-50 chromatography. The yield of growth factor is 5 mg per kg of pituitary. It is active in stimulating DNA synthesis in 3T3 cells at concentrations as low as 2 times 10-13 M with saturation at 1 times 10-10 M.

Amino Acids↗
PubMed1975

Mitogenic effect of fibroblast growth factor on early passage cultures of human and murine fibroblasts.

Fibroblast growth factor (FGF), a polypeptide that has been shown to stimulate division in 3T3 cells, was tested for mitogenic effects on diploid, early-passage cells from human and murine sources. The quantitative assay of [3H]thymidine incorporation into acid-insoluble material showed that FGF at low concentrations (10 minus 9 M) was more effective than additional serum for provoking the initiation of DNA synthesis in human foreskin fibroblasts or mouse fibroblasts maintained in 5 or 10% serum, respectively. The growth of the human fibroblasts was twice as fast in the presence of FGF plus 10% calf serum as it was in the presence of 10% calf serum or 20% fetal calf serum alone. The addition of FGF to primary cultures of mouse fibroblasts in 0.4% serum resulted in a twofold increase in cell number compared to controls. In contrast to results obtained with 3T3 cells, neither insulin nor a glucocorticoid potentiated the effects of FGF on either human or mouse cells.

Animals↗
PubMed1975

The morphological transformation and inhibition of growth of bovine luteal cells in tissue culture induced by luteinizing hormone and dibutyryl cyclic AMP.

The luteal cells obtained from bovine corpus luteum by enzymatic treatment have been maintained in tissue culture. When the cells were maintained in the absence of luteinizing hormone or dibutyryl cyclic AMP, they grew parallel to one another and were elongated, thus giving to the culture a fibroblastic appearance. No contact inhibition was observed and the progestin secretion rate was low (3 pg per cell per day). In contrast, when luteinizing hormone or dibutyryl cyclic AMP was present, the cells became polygonal, growing as a monolayer and taking the appearance of epithelial cells. In this case contact inhibition was observed. The rate of progestin secretion was 250 pg per cell per day. As soon as luteinizing hormone or dibutyryl cyclic AMP was removed from the media, the cells reverted to a fibroblastic appearance. Agents such as colcemid, vinblastin or cytochalasin B inhibited the morphological effect of luteinizing hormone or dibutyryl cyclic AMP. Since those agents are known to inhibit the assembly of microtubules, the data suggest that LH and dibutyryl cyclic AMP act by promoting the organization of microtubules from protein monomers. This microtubular system (cytoskeleton) is responsible for the morphological appearance of the cells. Concomitant with the morphological changes induced by luteinizing hormone and dibutyryl cyclic AMP an inhibition in the growth rate of luteal cells was observed. It suggests that by raising the intracellular level of cyclic AMP the luteinizing hormone inhibits the division of luteal cells and is not, for that reason, a mitogenic agent. A similar effect was obtained with other agents known to stimulate cyclic AMP production such asthe prostaglandins. Steroids such as glucocorticoids and testosterone but not progesterone also inhibited the growth rate. It is concluded that luteinizing hormone by controlling the level of cyclic AMP within the luteal cells is responsible for the expression of the phenotype of the cells and the maintenance of differentiation.

Animals↗
PubMed1975

Stimulation of division of Y1 adrenal cells by a growth factor isolated from bovine pituitary glands.

The effect of Fibroblast Growth Factor (FGF) on the initiation of DNA synthesis and on the rate of division of the Y1 adrenal cell line has been investigated. In sparse populations of Y1 cells (4 times 10- minus 3 cells/cm2) maintained in 0.2 percent calf serum, FGF was able to initiate DNA synthesis to the same extent that an optimal concentration of serum could. Cells maintained in 0.2 percent calf serum sustained continuous growth when given 5 ng/ml of FGF daily. Cultures fixed and stained with crystal violet showed FGF colonies to be of equivalent size and quantity as those with serum alone. Insulin had no mitogenic activity of its own at concentrations as high as 500 ng/ml nor did it have any potentiating effect on the mitogenic activity of FGF. Glucocorticoids (0.1 mug/ml to 1 mug/ml) inhibited (25 percent) the initiation of DNA synthesis as well as the rate of division induced by FGF. ACTH (0.75 IU/ml) was clearly inhibitory. Not only did it reduce the rate of division of cells in serum but it also reduced the rate of DNA synthesis and inhibited division in the presence of FGF.

Adrenal Gland Neoplasms↗
PubMed1975

Comparison of the binding of human chorionic gonadotropin to isolated bovine luteal cells and bovine luteal plasma membranes.

The specific binding of [125-I]iodohCG to intact luteal cells obtained from bovine corpus luteum by enzymatic treatment, or to purified plasma membranes obtained from bovine corpus luteum has been compared. It was a saturable process with respect to the [125-]iodohCG concentration. Specific binding could be detected at concentrations as low as 1.8 ng of HCG per ml and saturation achieved at 92 ng/ml. The [125-I]iodohCG specifically bound to the luteal cells or to the plasma membranes was displaced by increasing concentrations of native hCG. Subunits hCGalpha and beta had respectively 200- and 800-fold less activity than hCG. Four to 10 times more ovine LH than hCG was required to displace an identical amount of bound [125-I]iodohCG. The binding of hCG to its receptor site was a function of time and temperature. The affinity of hCG for its receptor sites in luteal cells or plasma membranes of luteal cells was similar (dissociation constants of 5.3 and 3.8 times 10- minus 10 M, respectively). The number of sites per luteal cell was 5 times 10-4 and the capacity of plasma membranes to bind hCG was 140 fmol per mg of protein at saturation. The data does not, however, allow a comparison between the number of binding sites in the two preparations. It is concluded that the enzymatic treatment necessary to obtain a suspension of viable luteal cells does not affect the kinetic characteristics of the binding of hCG to receptor sites since they are similar to those of plasma membranes not treated with proteolytic enzymes.

Animals↗
PubMed1974

Stimulation of division of sparse and confluent 3T3 cell populations by a fibroblast growth factor, dexamethasone, and insulin.

The stimulation of division of Balb/c 3T3 mouse fibroblasts by fibroblast growth factor alone and in combination with insulin and a glucocorticoid (dexamethasone) has been investigated. Fibroblast growth factor stimulates DNA synthesis in sparse, quiescent cultures maintained in a low serum concentration, but does not support more than two division cycles. In the presence of dexamethasone, the growth factor supports continuous division cycles. The addition of insulin significantly augments the response to fibroblast growth factor alone and slightly augments the response to growth factor plus dexamethasone. Fibroblast growth factor stimulates the division of confluent, quiescent cultures grown in 10% serum. When growth factor plus dexamethasone is added to such cultures, "contact inhibition" is overcome.

Animals↗
PubMed1974

Effect of a fibroblast growth factor, insulin, dexamethasone, and serum on the morphology of BALB/c 3T3 cells.

The effects of serum, fibroblast growth factor, dexamethasone, and insulin on the morphology of two lines of BALB/c 3T3 cells are described and illustrated. Fibroblast growth factor, a polypeptide purified from bovine brain and pituitary glands, stimulates DNA synthesis and cell division in both sparse and confluent cultures of quiescent 3T3 cells. When cells are grown in the presence of the factor, they go through one or two cycles of division and their morphology differs from that of cells either growing in 10% serum or maintained in a quiescent state in low serum; they appear rounded with long processes and show no sign of contact inhibition. When dexamethasone is present with the growth factor, the cells grow to a high density and are not contact-inhibited; they have the appearance of transformed cells. Addition of insulin or dibutyryl cyclic AMP to the cells results in a morphology similar to that of cells growing in the presence of serum. Addition of growth factor or growth factor plus dexamethasone to cells that have reached confluency in 10% serum and that are clearly contact-inhibited results in the resumption of growth. The final cell density reached is similar to that of cells growing in the presence of 30% serum with daily fluid changes. No contact inhibition is observed in either of these situations.

Animals↗
PubMed1974

Purification of a growth factor for ovarian cells from bovine pituitary glands.

The purification of a growth factor from bovine pituitary glands that controls the division of an ovarian cell line maintained in tissue culture is reported. Extraction of bovine pituitary glands at pH 4.5 followed by ammonium sulfate precipitation, chromatography on carboxymethylcellulose, and gel filtration on Sephadex G-50 gives yields of ovarian growth factor of about 7 mg/kg of glands. Contamination by other pituitary hormones was not detected. The preparation obtained has been characterized with respect to biological activity, molecular weight, and amino-acid composition. The implication of this growth factor in the development of ovarian tumors is discussed.

Amino Acids↗
PubMed1974

Growth control in cultured mouse fibroblasts: induction of the pleiotypic and mitogenic responses by a purified growth factor.

Addition of serum to quiescent mouse fibroblasts induces a series of macromolecular changes (a pleiotypic response) followed by DNA synthesis and cell division. A new pituitary hormone, fibroblast growth factor, and hydrocortisone acting at physiological concentrations can completely replace exogenously added serum for the induction of these events in lines of BALB/c 3T3 cells. The induction of cell growth is specific for cultured fibroblasts; no stimulation is observed for mouse epithelial cells or virally transformed fibroblasts.

Animals↗
PubMed1974

Biological activity of a growth factor for ovarian cells.

The biological activity of a protein growth factor is described. This factor was isolated from bovine pituitary tissue, and its activity was tested on cells of rat ovarian origin. Activity was assayed as growth-promoting potential measured by cell counts and is concentrationdependent. Similar growth stimulation was not produced by several cyclic nucleotides tested, neither was there crossreactivity between this growth factor and a chemically similar one produced by rat liver cells.

Animals↗