Search PubMed⌕ Search

Biomedical subjects

D W Golde

Publications and source records attributed to D W Golde.

At least 217 records · Page 12Linked to original sources
PubMed1983

Proliferation of human malignant hematopoietic cells in immunodeficient mice: suppression by antibody to pluripotent K-562 leukemia cells involves direct cytolysis and effector cells.

Six human hematopoetic cell lines were successfully heterotransplanted into athymic (nude) and asplenic-athymic (lasat) neonatal mice. The tumors arising from leukemia and lymphoma cells could then be serially transplanted into adult nude mice. Seven days after the fourth serial mouse passage, each mouse was treated with goat immune gamma globulin against K-562 cells. One control group was treated similarly, but with nonimmune (normal) gamma globulin, while another control group was not treated. The goat gamma globulin was not toxic for nude and lasat mice, and the immune, but not the normal, gamma globulin suppressed local subcutaneous growth of myelosarcomas, lymphosarcomas, and Burkitt lymphoma cells. On the other hand, the growth of lung, breast, and prostatic carcinomas and a melanoma of human origin were not altered by the immune gamma globulin. Since suppression of cell growth occurred equally well in decomplemented mice, a complement-mediated cytotoxicity apparently cannot be considered as responsible for the abrogation. The Fab fragment of the immunoglobulin did not suppress the growth of the myelosarcomas. We conclude that antibody suppression of the in vivo proliferation was specific for malignant hematopoietic cells and that the Fc portion of IgG is necessary for in vivo cytolysis of leukemia cells. The most probable mechanisms are direct antibody cytolysis and antibody-dependent macrophage-mediated cytotoxicity.

Adenocarcinoma↗
PubMed1983

Lymphokines secreted by an established lymphocyte line modulate receptor-mediated endocytosis in macrophages derived from human monocytes.

As little as 1 microliter of serum-free supernatant from Mo(t), an established lymphocyte line, when added to a 500-microliters incubation of macrophages derived from human monocytes, significantly decreased the receptor-mediated uptake and degradation of three cholesterol-rich molecules: low density lipoprotein (LDL); LDL complexed to dextran sulfate; and LDL modified by malondialdehyde (MDA-LDL). In contrast, the receptor-mediated uptake and degradation of mannosyl bovine serum albumin was increased three-fold. The Mo(t) supernatant did not contain competitive inhibitors of the cholesterol-rich ligands, and it did not alter macrophage receptor-independent endocytosis, protein synthesis, or phagocytosis of heat-killed yeast. The effect of the Mo(t) supernatant was specific for macrophages and was abolished by preincubation of the supernatant with trypsin, which indicates that the active substances are protein in nature. The decrease in the uptake and degradation of MDA-LDL induced by preincubating the macrophages with Mo(t) supernatant appeared to result from a decrease in the number of receptors for this ligand at the cell surface. The isolation of these lymphokines should offer new insights into macrophage receptor-mediated endocytosis, and may yield substances useful in preventing foam cell formation in atherosclerosis.

Cell Differentiation↗
PubMed1983

Association of the human type C retrovirus with a subset of adult T-cell cancers.

To determine whether the human T-cell lymphoma-leukemia virus (HTLV) is associated with particular cancers, patient sera were surveyed for HTLV-specific antibodies. An association was seen with aggressive cancers of mature T-cells, specifically Japanese adult T-cell leukemia (ATL) and T-cell lymphosarcoma cell leukemia (TLCL), a similar cancer of Caribbean blacks. Ninety to 100% of these patients possessed HTLV-specific antibody. Forty-seven and 20% of relatives of ATL and TLCL patients, respectively, and 12 and 4% of healthy donors from ATL and TLCL endemic areas were also antibody positive. Visceral organ involvement, hypercalcemia, and skin manifestation, features of ATL and TLCL, were often seen in other antibody-positive patients. Childhood cancers, most cutaneous T-cell and all non-T-cell leukemias and lymphomas, myeloid leukemias, Hodgkin's disease, and solid tumors were not associated with HTLV. Healthy United States donors and European patients with non-malignant diseases were antibody negative. HTLV is thus associated with a subtype of adult T-cell leukemia-lymphoma, clustered in viral endemic areas, with apparent racial and geographic predilection.

Adult↗
PubMed1982

Alveolar macrophage dysfunction in human bone marrow transplant recipients.

We studied the functional characteristics of alveolar macrophages obtained by segmental pulmonary lavage from allogeneic marrow transplant recipients without evidence of ongoing pulmonary infection. The macrophages were mostly of donor marrow origin as judged by Y body fluorescence and were morphologically normal, except for the intracellular accumulation of various amounts of heterogeneous foreign materials. Macrophage function of patients studied within four months after transplantation was impaired, as measured by chemotaxis, phagocytosis and killing of Candida pseudotropicalis, and killing of bacteria. In two patients studied six and 12 months after transplantation, macrophage functions returned toward normal except for a persistent defect in killing of C. pseudotropicalis. Cytomegalovirus was cultured from the lavaged cells of two patients, but the macrophage dysfunction was independent of the cytomegalovirus isolation. These results show that alveolar macrophage dysfunction occurs in marrow transplant recipients and may be associated with their increased risk for pulmonary infections.

Acute Disease↗
PubMed1982

Lithium enhances growth of human leukaemia cells in vitro.

Lithium is known to cause leucocytosis in normal humans, and lithium salts have been used therapeutically in attenuating leucopenia in patients undergoing chemotherapy. Recent reports also described leukaemia development during lithium treatment. We have investigated the effect of lithium chloride on the proliferation of human myeloid, erythroblastic, and T- and B-lymphoblast leukaemia cells in vitro. Colony formation by cells of the myeloid leukaemia lines HL-60 and KG-1 was enhanced by lithium chloride, and maximal stimulation was seen at 5 X 10(-4) M. Lithium also increased the proliferation of KG-1a cells, a subline of KG-1 cells that does not respond to colony-stimulating factor, indicating a direct growth-promoting effect on myeloid leukaemia cells. Lithium was found to enhance colony formation by the T-lymphoblast cell line MOLT 4 and the B-lymphoblast line IM-9 at concentrations between 10(-6) and 10(-3) M. The addition of lithium chloride to murine Friend or human K-562 erythroleukaemia cells also caused an augmentation in colony formation. These observations may have relevance to the therapeutic use of lithium in patients with haematological malignancies.

Animals↗
PubMed1982

Natural and biosynthetic insulin stimulates the growth of human erythroid progenitors in vitro.

High concentrations of insulin are known to augment the growth of various cell types in vitro. We examined the effect of a purified porcine insulin and biosynthetic human insulin produced in E. coli on the growth of human erythroid progenitors in vitro. Both insulins stimulated peripheral blood erythroid colony formation within the physiological range. An approximately 2-fold augmentation in colony formation was seen at insulin concentrations of 8 ng/ml, and as little as 0.1 ng/ml (0.17 nM) caused detectable stimulation of colony formation. The effect of subnanomolar concentrations of insulin or erythropoiesis in vitro suggests that insulin could modulate erythropoiesis in vitro. Human responsiveness to insulin's growth-promoting activity can be directly assayed in vitro using peripheral blood.

Adult↗
PubMed1982

Humoral stimulation of hemopoietic progenitors from human fetal liver.

Hemopoietic cells from human fetal livers of 9-21 weeks gestation were cultured in semisolid media in vitro and in diffusion chambers implanted in mice. Myeloid colony formation in agar (CFU-C) was detected only in the presence of colony-stimulating factor. Formation of erythroid bursts in vitro was enhanced by addition of erythropoietin or erythroid-potentiating activity derived from a human T cell line (Mo). Fetal liver cells implanted in diffusion chambers gave rise to myeloid (CFU-DG) and occasionally to erythroid colonies. Administration of colony-stimulating factor derived from the T cell line to the host mice did not effect CFU-DG numbers. In contrast, a partially purified preparation containing erythroid-potentiating activity, caused a significant increase in the formation of CFU-DG. Similar stimulation was achieved by pretreatment of the diffusion chamber hosts with cyclophosphamide. None of these manipulations effected erythroid colony formation in diffusion chambers in mice.

Animals↗
PubMed1982

Antibody lysis of human hematopoietic cells in the absence of complement and effector cells.

The incubation of K-562 leukemia cells with specific goat immunoglobulin resulted in gradual cytolysis in the absence of complement and effector cells. Optimal lysis (100%), reached in 3-4 days, occurred when the concentration of the antibody in the culture medium was about 20 micrograms/ml containing an initial inoculum of 15,000 cells. A lower concentration (10 micrograms/15,000 cells/ml) led to partial cytolysis; the surviving cells, cultured in fresh medium, were still vulnerable to antibody lysis (30 micrograms/ml), thus indicating the lack of an apparent resistant cell population. The amount of free antibody in the culture medium diminished rapidly and very little or none was detectable after 2-3 hours of incubation with K-562 cells. The immune gamma-globulin also inhibited colony formation of K-562 cells in soft agar. The immune gamma-globulin, absorbed extensively with normal blood cells, to pluripotent K-562 cells, cross-reacted with several human malignant hematopoietic cell lines tested. These cells included T-lymphoblasts (JM and MOLT-4), promyelocytes (HL-60), Burkitt's lymphoma cells (RAJI), myeloblasts (KG-1 and KG-1a), and multiple myeloma cells (K-737). The absorption of the immune gamma-globulin with an equal number of cells from each of the cell lines assayed diminished but did not completely remove the antibody responsible for cytolysis of K-562 target cells. Thus, the K-562 leukemia blasts appear to possess common and specific antigens that may be only partially expressed on other committed leukemia cell lines studied. For this reason, the cytolytic activity of the immune gamma-globulin could only be removed by absorption with K-562 cells possessing a complete array of antigens solely present on pluripotential hematopoietic cells.

Antibodies↗
PubMed1982

Human leukemia cell line K562 responds to erythroid-potentiating activity.

We report that erythroid-potentiating activity (EPA), known to stimulate the proliferation of normal human erythroid precursors in vitro, has a growth-promoting effect on human K562 erythroleukemia cells and Friend mouse erythroleukemia cells. Detailed studies were carried out using an EPA produced by a human T-lymphoblast line (Mo). Although EPA has not been purified to homogeneity, several observations indicate that the factor elaborated by Mo cells that stimulates erythroleukemia cell growth is the EPA molecule. The erythroleukemia growth factor cofractionates with EPA using gel exclusion chromatography, isoelectric focusing, and ion exchange chromatography. In addition, the activities exhibit similar kinetics of heat inactivation. A granulocyte-macrophage colony-stimulating factor also elaborated by Mo cells had no effect on the growth of the erythroleukemia cells. Other sources of EPA, such as peripheral blood leukocyte-conditioned medium, preparations from urine of anemic patients, and medium conditioned by a human monocyte-like cell line, stimulated erythroleukemia cell growth. Mouse sources of EPA (termed "burst-promoting activity") stimulated mouse but not human erythroleukemia cells. The availability of cell lines apparently responsive to EPA should prove useful for examining the mode of action of this regulator of erythropoiesis.

Animals↗
PubMed1982

Human T-lymphocyte products stimulate human hemopoietic progenitor cell proliferation in diffusion chambers in vivo.

Human myeloid colony formation in diffusion chambers in mice (CFU-DG) was enhanced following administration of a human T-cell-line-derived conditioned medium (Mo). The Mo cell line also elaborates activities stimulating human myeloid colony formation in vitro in agar (CSF) and potentiating erythroid colony formation in vitro in methylcellulose (EPA). Depletion of CSF from Mo conditioned medium by heat inactivation or gel exclusion chromatography did not affect CFU-DG formation. EPA and CFU-DG stimulating activities are heat stable and have approximately the same molecular weight. Culture of human bone marrow cells in diffusion chambers in mice for 4 days under the influence of Mo conditioned medium resulted in significant increment of BFU-E and CFU-DG as judged by subculture of diffusion chamber contents. No effect on CFU-C could be detected.

Animals↗
PubMed1982

Surface morphology and functional studies of human alveolar macrophages from cigarette smokers and nonsmokers.

The surface of macrophages inhabiting the peritoneal and alveolar spaces is pleomorphic in structure. The internal structure of these cells has been widely described and is not discussed here. Although external cell morphology has been well characterized by many researchers, this subject has not been reviewed. This review, therefore, describes in detail the surface features of macrophages as well as factors affecting macrophage morphology. Morphological studies of human cells are emphasized. Functional studies are presented and, when possible, morphological parameters are correlated with cell function. Because cigarette smoking has been well studied, the effects of this pulmonary insult are described in detail.

Anesthetics, Local↗
PubMed1982

Functional evaluation of lung macrophages from cigarette smokers and nonsmokers.

The in vitro function of pulmonary alveolar macrophages (PAM) was compared for human smokers and nonsmokers. Initial studies demonstrated the feasibility of shipping lavaged cells on ice with storage up to 6 hr. Comparative studies were performed to evaluate ideal culture conditions including media composition, preincubation period, and phagocytic variables. Smokers had a six-fold enhancement in lavagable macrophages compared to nonsmokers. Macrophages from smokers demonstrated a decreased phagocytic capability compared to nonsmokers. The effects of cigarette smoking on phagocytosis were observed over a wide range of challenge periods using either fetal or newborn bovine serum (FBS or NBS). Regardless of smoking history, enhanced phagocytosis was observed with media containing NBS compared to FBS. No effects on in vitro viability, attachment, or adherence were observed.

Adult↗
PubMed1981

Growth hormone stimulates drug-induced porphyrin formation in liver cells maintained in a serum-free medium.

Human growth hormone and a few other related polypeptide hormones enhanced porphyrin formation induced by 2-allyl-2-isopropylacetamide in chick embryo liver cells maintained in a serum-free medium. The stimulatory effect of human growth hormone on drug-induced porphyrin formation was significant at 10 ng/ml and increased in a dose-dependent manner. Human growth hormone did not stimulate porphyrin formation in otherwise untreated cultures. These findings thus demonstrate a potentiating effect of growth hormones on hepatic porphyrin formation.

8-Bromo Cyclic Adenosine Monophosphate↗