Search PubMed⌕ Search

Biomedical subjects

D W Golde

Publications and source records attributed to D W Golde.

At least 253 records · Page 14Linked to original sources
PubMed1980

Growth hormone polypeptides stimulate proliferation of K562 human erythroleukemia cells.

The growth-promoting effect of growth hormones and related polypeptides was examined in vitro with a clonogenic assay using human erythroleukemic cells (K562). The erythroleukemia cells were grown in a serum-substituted methylcellulose culture system and colonies counted after 4 days' incubation. Human growth hormone (hGH) was a potent stimulant for K562 cell growth (60% augmentation). The cys(Cam)53-hGH(1-134) fragment of hGH and human chorionic somatomammotropin had less than half the activity of the intact hGH molecule. Bovine growth hormone was inactive in enhancing K562 colony formation. K562 cell proliferation was stimulated by hGH at concentrations as low as 0.1 ng/ml. Insulin stimulated K562 cell proliferation most effectively at a concentration of 1 ng/ml. The K562 culture system may conveniently be employed for determining the in vitro bioactivity of hGH.

Cell Division↗
PubMed1980

Human preleukemia.

Preleukemia refers to the syndrome of hematopoietic dysfunction seen in some patients before typical features of acute myelogenous leukemia develop. Clinically, preleukemia is characterized by variable degrees of pancytopenia, with associated symptoms due to decreased circulating blood elements. The bone marrow is usually hypercellular, and there are prominent morphologic abnormalities in erythroid precursors and more subtle changes in megakaryocytes and granulocyte progenitors. During this phase of the leukemic process, the neoplastic clone is usually already established and predominant. A clear distinction should be made between the preleukemic syndrome and diseases that predispose to development of acute myelogenous leukemia. Preleukemia, like acute myelogenous leukemia, is a clonal hematopoietic stem cell neoplasm manifested functionally by abnormal hematopoietic cell maturation and ineffective hematopoiesis. During the course of preleukemia, precursor cell maturation becomes progressively impaired with termination in the severe maturational block characteristic of acute myelogenous leukemia. We favor the concept that preleukemia is an early phase of acute myelogenous leukemia.

Bone Marrow↗
PubMed1980

Effect of burst-promoting activity (BPA) and erythropoietin on hemoglobin biosynthesis in culture.

The influence of erythropoietin (Ep) and burst-promoting activity (BPA) on the relative rates of synthesis of fetal and adult hemoglobins (HbF and HbA) were investigated in clonal cell culture. In the case of crude Ep, a positive dose-response relationship between the concentration and the relative rate of HbF biosynthesis by circulating erythropoietic precursors was clearly observed. In contrast, increasing the concentration of purified Ep enhanced the synthesis of HbF and HbA equally. BPA from bone marrow conditioned media and T-cell conditioned media enhanced the relative rate of HbF biosynthesis and burst number at limiting serum concentrations (10%-15%). We, therefore, conclude that BPA is important in the modulation of HbF biosynthesis in culture.

Animals↗
PubMed1980

Amygdalin (Laetrile): effect on clonogenic cells from human myeloid leukemia cell lines and normal human marrow.

The effect of amygdalin on human acute myelogenous leukemia cells and normal bone marrow granulocyte-monocyte precursors was studied in vitro using soft-gel culture. A pharmaceutical and a clinical source of amygdalin were tested and beta-glucosidase was added to selected cultures to promote the hydrolysis of amygdalin. Acute myelogenous leukemia cells were obtained from two human cell lines designated KG-1 and HL-60. A 50% inhibition of colony formation by both normal and leukemic cells was observed at an amygdalin concentration of 3.5 mg/ml using both drug sources. We found the colony-forming cells from the leukemic cell lines and normal marrow to be relatively resistant to amygdalin and its metabolites in vitro, and there was no selective kill of clonogenic cells from the human leukemia cell lines as compared to normal bone marrow.

Amygdalin↗
PubMed1980

Hormonal effects on cell proliferation in a human erythroleukemia cell line (K562).

We have investigated the hormonal responsiveness of K562 cells using a serum-substituted in vitro clonogenic assay. Dexamethasone inhibited colony formation by the K562 cells, and the inhibitory effect could be reversed by progesterone (10(-6) M). Fluoxymesterone caused a prominent enhancement of K562 colony growth, whereas estriol had no effect. Stimulation by triiodothyronine was maximal at 10(-7) M, and the thyroid effect could be abrogated by the beta 2-adrenergic antagonist butoxamine in equimolar concentrations. Using standard tissue culture conditions, the beta-adrenergic agent isoproterenol, but not the alpha catecholamine phenylephrine, enhanced the proliferation of K562 cells. When K562 cells were grown under hormone-depleted conditions, they developed responsiveness to phenylephrine and were no longer stimulated by isoproterenol. DbcAMP and prostaglandins of the E series also caused K562 colony enhancement. Prostaglandin F2 alpha had no effect on cell proliferation. Insulin was an effective stimulant of colony formation of K562 cells, as were human growth hormone and ovine prolacin. Bovine growth hormone had no effect. Our results are consistent with the identificaiton of K562 as an erythroid line, and they indicate that K562 cells respond to endocrine hormones in a manner analogous to normal erythroid progenitors.

Butoxamine↗
PubMed1980

Glucocorticoid sensitivity and receptors in cells of human myelogenous leukemia lines.

The effect of dexamethasone on the clonal proliferation of human acute myelogenous leukemia cells was studied using the two available human acute myelogenous leukemia lines KG-1 and HL-60. The cells were cloned in agar in the presence of colony-stimulating activity with and without dexamethasone. Colony formation by KG-1 cells was inhibited by dexamethasone at a concentration of 10(-7) M, and a 50% reduction occurred at 10(-5) M dexamethasone. Dexamethasone had no effect on HL-60 colony formation. Direct assessment of dexamethasone binding showed that both KG-1 and HL-60 cells had high-affinity glucocorticoid receptors with a mean 10,300 and 15,600 binding sites/cell with a Kd of 3.3 x 10(-9) M and 4.2 x 10(-9) M (r greater than or equal to -0.95), respectively. Binding competition studies confirmed the specificity of these glucocorticoid receptors. No correlation was noted between the number of glucocorticoid receptors and the in vitro inhibition of colony formation. A variety of other steroids was tested and found to have no effect on clonal proliferation of the leukemic cells.

Binding, Competitive↗
PubMed1980

An undifferentiated variant derived from the human acute myelogenous leukemia cell line (KG-1).

A variant subline (KG-1a) of the human acute myelogenous leukemia (AML) cell line (KG-1) has been isolated. The cells retain the same constitutive markers as the parent line, including HLA antigens, isoenzymes, and karyotype. The cells from the subline are morphologically and histochemically undifferentiated blast cells, while the parent cells and several of its clones are at the myeloblast and promyelocyte stages of development. The variant cells do not respond to colony-stimulating factor (CSF), and they do not express the human la antigen, nor a recently characterized AML antigen. The parent KG-1 cells are stimulated to proliferate in the presence of CSF and the cells express the la and AML antigen. Variant AML cell lines, such as KG-1a, will be useful in vitro models for investigating cellular response to CSF and for studying antigen expression in leukemic cells.

Cell Line↗
PubMed1980

Erythroid-potentiating activity: characterization and target cells.

We established a human T-lymphoblast cell line (Mo) that produces factors stimulating the proliferation of hematopoietic cells. These include a colony-stimulating factor for normal human granulocytes and macrophages, and a factor with erythroid-potentiating activity (EPA) that enhances the proliferation of normal human erythroid progenitors in vitro. Erythroid-potentiating activity has been partially purified and characterized. It is an acidic glycoprotein of 45,000 daltons molecular weight and it has remarkable heat stability. Erythroid-potentiating activity is physically separable from the colony-stimulating factor. Partially purified EPA was found to stimulate the proliferation of human K-562 and murine Friend erythroleukemia cells. These erythroleukemia cell lines may therefore prove useful for studying the action of EPA on target cells. Erythroid-potentiating factors from other human and murine sources stimulated erythroleukemia cell proliferation in a manner indicating some species restriction. Purification and structural analysis of the EPA molecule will ultimately be required in order to determine the details of its biologic action and to define its relationship to other erythropoietic factors.

Animals↗
PubMed1980

Ia antigen is a differentiation marker on human eosinophils.

Evidence suggests that the "la-like" or antigen is a differentiation marker that is expressed on early human hematopoietic precursor cells, but is absent on their mature progeny. The eosinophil precursor cell (CFU-EO) is distinct from the granulocyte-monocyte colon-forming cell (CFU-C). We provide data that indicate that the ia antigen is expressed on the human eosinophil colony-forming cells and is absent on mature eosinophils. All CFU-EO were inhibited in the presence of rabbit la antiserum at a titer of 1:30. Cytotoxicity was complement-dependent. The metamyelocytic eosinophil and more mature eosinophil forms did not express the la antigen.

Antigens, Surface↗
PubMed1980

Impaired cellular interactions involving lymphocytes from patients with chronic lymphocytic leukemia and ataxia-telangiectasia.

Abnormal cellular interactions between T and B lymphocytes were identified in patients with CLL and AT. The system employed utilized the detection of a newly recognized lymphokine, NIF-T. This mediator is produced by T lymphocytes as a result of the interaction between T and B cells. Our studies demonstrated impaired T cell function but normal B cell activity in patients with AT with respect to mitogenic stimulation and MLC reactivity. In contrast, patients with B cell CLL had normal T cell function. The leukemic B cells from these patients, however, failed to collaborate with normal T cells in response to mitogens, and they did not participate in MLC reactions. In contrast, lymphocytes from patients with HCL functioned normally with respect to NIF-T production.

Adult↗
PubMed1980

Human myeloid leukemia cell lines: a review.

Several human acute myeloid leukemia cell lines were recently established. These lines provide model systems to study the control of differentiation in human myelogenous leukemia and, in a broader framework, the controls of normal myeloid development. The K562 line is composed of undifferentiated blast cells that are rich in glycophorin and may be induced to produce fetal and embryonic hemoglobin in the presence of hemin. The KG-1 cell line is composed predominantly of myeloblasts and promyelocytes. A unique characteristic of the KG-1 cells is their almost complete dependence on colony-stimulating factor for proliferation in soft-gel culture. The HL-60 is a promyelocytic leukemia cell line. In the presence of DMSO, the cells mature into granulocytes. Both the KG-1 and HL-60 cells differentiate into nondividing mononuclear phagocytes when exposed to phorbol esters. Investigations with these cell lines, and selected variants should provide important insights into the cell biology and perhaps therapy of human leukemia.

Antigens, Surface↗
PubMed1980

Myeloid colony-forming cell kinetics in man.

To determine the half-life of circulating myeloid colony-forming cells (CFUc) in man, we studied circulating CFUc in the blood of transplant recipients after the infusion of donor marrow. The agar culture technique was used to clone peripheral blood granulocyte-monocyte progenitors. Circulating CFUc were rare before donor marrow infusion. After infusion of a large number of donor progenitor cells, there was a rapid, linear decrease in myeloid colony-forming cells in the patients' blood. The mean half-life for the circulating CFUc was 4.6 h. No correlation was noted between maximum number of circulating CFUc and the disappearance rate from the blood. A rapid increase in circulating CFUc occurred simultaneously with marrow engraftment.

Adolescent↗
PubMed1980

Long-term human bone marrow cultures.

Pronlonged in vitro growth of murine bone marrow has been achieved using a flask culture system. We report the adaption of the technique to the growth of human bone marrow. In this system, CFU-GM and CFU-E are maintained for 4-9 wk. Morphologically recognizable granulopoiesis occurs for 4-6 wk and erythropoiesis for 1.5-2.5 wk. Functional T lymphocytes are maintained for at least 5 wk. The adherent population is composed of macrophages, fibroblast-like cells, and flat pavement-like cells. Fat-containing cells are not prominant. This culture system provides a means to study human hematopoietic cell proliferation and differentiation in vitro, as well as to examine interactions between stromal cells and hematopoietic and lymphoid progenitors.

Bone Marrow↗
PubMed1980

Morphological studies of cultured human pulmonary macrophages.

A morphological classification scheme is developed for the quantitative in vitro examination, by scanning electron microscopy (SEM), of pulmonary alveolar macrophages (AM) from human cigarette smokers and nonsmokers. The AM were obtained by bronchopulmonary lavage, allowed to attach to glass coverslips in a serum containing medium, cultured for 1, 2, or 25 hours, and examined in the SEM. Fifty cells per sample were randomly selected for detailed morphological analysis using a predetermined sampling grid. Area, form, degree of cell spreading, and the relative abundances of surface features, including ruffles, filopodia, blebs, microvilli, multiple features, and no surface features were quantified. Smoker AM had a greater incidence of ruffles, filopodia, multiple features, and rounded cells; nonsmoker AM had greater incidences of featureless and spread cells. Microvilli and blebs were observed infrequently and displayed no trends with respect to differences between smokers and nonsmokers. The incidence of filopodia, multiple features, and intermediate shapes generally increased with increasing culture time, and a decreasing incidence with increasing time in culture was observed for featureless and spread cells. For the 1- and 2-hour culture periods, slightly greater sizes, size variances, form factors, and form factor variances were observed for smoker AM; however, after 25 hours in culture, nonsmoker AM populations possessed these characteristics. Area frequency distributions appeared to be logarithmically normal in distribution. Statistical analyses indicated that for area and form, the greatest variance was due to variations among the individuals lavaged.

Cell Adhesion↗