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Biomedical subjects

D W Golde

Publications and source records attributed to D W Golde.

At least 235 records · Page 13Linked to original sources
PubMed1981

Purification and crystallization of the polypeptide hormone human chorionic somatomammotropin.

We have purified the large polypeptide hormone human chorionic somatomammotropin to near electrophoretic homogeneity by a new purification scheme. The hormone crystallized from polyethylene glycol in a form suitable for high resolution x-ray analysis; the crystals are monoclinic, space group C2, a = 123.9, b = 30.3, c = 53.8 A, beta = 119 degrees 30 min, with 1 molecule/asymmetric unit. The growth-promoting activity of homogeneous hormone and of dissolved crystals was measured through their effect on committed erythroid precursor cells in tissue culture assays. Both homogeneous and redissolved crystalline hormone had activities comparable to that of hormone purified by standard procedures. The latter preparations yielded either no crystals, or disordered crystals unsuitable for x-ray analysis.

Biological Assay↗
PubMed1981

The histiocytic disorders: a pathophysiologic analysis.

The histiocytoses are a diverse group of disorders involving cells of the mononuclear phagocyte series. These diseases are usually characterized by proliferation and activation of macrophages caused either by external stimuli or by an intrinsic cellular abnormality. We propose that these conditions be classified as reactive histiocytosis (inciting agent known or unknown), lipid storage disorder, and mononuclear phagocyte neoplasia based on apparent cause and natural history. Recent knowledge of monocyte-macrophage development and function allows for construction of pathophysiologic models of diseases formerly approached in a descriptive fashion. Macrophage activation appears to mediate many clinical features of th histiocytic disorders, such as hemophagocytosis, fever, and osteolysis. Further understanding of the pathogenesis of the histiocytic disorders should lead to improved therapy.

Eosinophilic Granuloma↗
PubMed1981

Polycythemia: mechanisms and management.

The principal function of erythrocytes is the transport of oxygen. Erythropoiesis proceeds at a rate consistent with the demand for oxygen-carrying capacity, and the major regulator of erythrocyte production is erythropoietin. Erythropoietin is produced primarily by the kidney under control of a tissue oxygenation sensor. The recently developed erythropoietin radioimmunoassay should provide a clinically useful tool. Erythrocytosis is a pathologic state characterized by an elevated erythrocyte mass, which may result from increased proliferation of erythroid progenitors due to an intrinsic cellular defect or in response to extrinsic signals. Secondary erythrocytosis results from either physiologically appropriate compensation for inadequate tissue oxygenation or from inappropriate stimulation of erythropoiesis. Erythrocytosis increases oxygen-carrying capacity of the blood, but at high hematocrit levels increased blood viscosity may result in decreased tissue oxygen delivery. Polycythemia vera is a hematopoietic stem cell disease of clonal origin. Initial results from the Polycythemia Rubra Study Group suggest that therapy with chlorambucil is associated with an unacceptably high risk for development of acute leukemia, and 32P is preferred for situations in which phlebotomy alone is insufficient.

Blood Gas Analysis↗
PubMed1981

Beta 2 receptor-mediated stimulation of Friend erythroleukemia cell growth by thyroid hormones.

Thyroid hormones are known to enhance normal erythroid colony growth (CFUE) and this enhancement depends on a functional beta 2-adrenergic receptor mechanism. we investigated the response of Friend cells to thyroid hormones, catecholamines, and other compounds influencing cellular cAMP activity. The thyroid hormones L-T3, L-T4, and "reverse T3" stimulated erythroleukemia colony growth in a serum-substituted methylcellulose culture system with peak activity at 10(-7) M. Various beta-adrenergic compounds enhanced Friend leukemia colony growth; however, the alpha-adrenergic agonist phenylephrine was inactive. Dibutyryl cyclic AMP and the phosphodiesterase inhibitor theophylline also enhanced Friend leukemia colony formation. Adrenergic antagonists with beta 2 specificity abrogated the stimulatory effect of L-T3, L-T4, and of "reverse T3" at equimolar concentrations. These experiments demonstrate that thyroid hormones, beta-adrenergic agonists, the phosphodiesterase inhibitor theophylline, and dbcAMP have a direct effect on the proliferation of Friend erythroleukemia cells. We conclude that thyroid hormones' action requires a functioning beta 2-adrenergic receptor mechanism. Thyroid hormones directly modulate the growth of neoplastic erythroid cells in a manner consistent with their effects on normal erythropoiesis.

Animals↗
PubMed1981

Purification and characterization of a human T-lymphocyte-derived granulocyte-macrophage colony-stimulating factor.

We have examined the biologic and physical properties of a human T-lymphocyte granulocyte-macrophage colony-stimulating factor (CSF). The source of the factor is a T-lymphoblast cell line (Mo) that was derived from a patient with a T-cell variant of hairy-cell leukemia. The Mo line constitutively produces a number of lymphokines that are normally produced by mitogen-stimulated T lymphocytes. Medium conditioned by Mo cells grown in the absence of serum is especially rich in CSF activity, and using this source we have purified the CSF to a specific activity of about 3.5 x 10(6) colonies per 10(5) Ficoll-Hypaque-separated human bone marrow cells plated per mg protein. The Mo CSF stimulates the formation of both granulocyte and macrophage colonies in vitro (in about equal numbers) and it has a relatively steep dose-response curve. Both the crude and purified preparations stimulated the formation of eosinophil as well as neutrophil colonies; it is unclear whether this is due to the presence of multiple factors with similar physical properties or a single factor with multiple activities. The CSF has little stimulating activity for mouse bone marrow progenitors. Physically, the Mo CSF is an acidic glycoprotein of molecular weight about 34,000. It binds to concanavalin A-Sepharose, is unusually resistant to denaturing agents and heat treatment, and is not inactivated in the presence of sulfhydryl reagents. The Mo CSF is distinct from factors stimulating erythroid colony formation and inhibiting neutrophil migration that are also produced by Mo cells. It differs in several physical and biologic properties from other human CSFs that have been characterized.

Cell Line↗
PubMed1981

Growth hormone stimulation of normal and leukemic human T-lymphocyte proliferation in vitro.

In order to investigate the effect of human growth hormone on T lymphocytes, we utilized a clonogenic assay for mitogen-responsive human peripheral blood T lymphocytes. Lymphocytes were purified by density gradient centrifugation and incubated in the presence of phytohemagglutinin using a two-layer agar technique for CFU- T-lymphocyte culture. Nanogram concentrations of human growth hormone, ovine prolactin, human chorionic somatomammotropin, or growth hormone fragment were added to cell cultures. Growth hormone potentiated normal T-cell colony formation in a species-specific manner. Cells from a homogeneous T-lymphoblast line derived from a patient with a T-cell variant of hairy cell leukemia also showed augmentation of colony growth in the presence of human growth hormone. These studies provide evidence for a direct effect of growth hormone on normal and some neoplastic human T cells.

Animals↗
PubMed1980

Splenic artery embolization prior to splenectomy in end-stage polycythemia vera.

A patient with polycythemia rubra vera and myeloid metaplasia required splenectomy because of local symptoms attributable to a massively enlarged spleen. Preoperative embolization of the splenic circulation with inert materials was performed to reduce splenic size and vascularity in order to permit safe splenectomy. This case illustrates the utility of preoperative splenic embolization when routine splenectomy is contraindicated for technical reasons. The hazards of this technique and guidelines for its clinical use are outlined.

Aged↗
PubMed1980

Production of erythroid-potentiating activity by a human T-lymphoblast cell line.

We derived a human T-lymphoblast cell line (Mo) that constitutively elaborates certain lymphokines. The Mo cells produce a colony-stimulating factor necessary for the growth of human granulocyte-monocyte precursors in vitro as well as an erythroid-potentiating activity (EPA) that enhances the proliferation of human erythroid progenitors in vitro. In the presence of serum, the EPA in Mo-conditioned medium stimulated the growth of small and large erythroid colonies almost 2-fold. EPA was also produced in serum-free medium, and, when assayed in serum-free cultures of human erythroid progenitors, it stimulated colony growth about 3-fold. The EPA produced by the Mo cell line did not stimulate normal murine erythroid progenitors (CFU-E) or Friend erythroleukemia cell growth in vitro. EPA was inactivated by protease treatment but was remarkably heat stable, with most of the activity recovered after boiling for 15 min. Preliminary biochemical characterization suggests that EPA is an acidic glycoprotein with molecular weight approximately 45,000. EPA is clearly separable from colony-stimulating factor on the basis of heat stability and gel-filtration chromatography. The present observations provide strong support for the concept that activated T cells produce humoral factors important in the regulation of erythropoiesis. The availability of a cell line producing human EPA should facilitate the characterization of the protein and permit definitive studies of its biologic effects.

Cell Line↗
PubMed1980

Origin of human bone marrow fibroblasts.

We investigated the origin of bone marrow fibroblasts in three bone marrow transplant recipients with aplastic anaemia and leukaemia who received grafts from HLA-identical siblings of opposite sex. The patients were conditioned for transplantation with high doses of cytotoxic drugs and 300--1000 rads total body irradiation. After transplantation, bone marrow cells were cultured in T flasks for 3 weeks and the adherent cells were then trypsinized and passaged weekly. After several passages the cells had the typical morphology and growth pattern of fibroblasts. Metaphases from these cells were all of recipient sex type. In contrast, haematopoietic cells and lymphocytes obtained at the same time were of donor sex type. Our findings indicate that the human bone marrow fibroblast is not derived from a precursor common to haemotopoietic cells or lymphocytes. The bone marrow fibroblast appears to be a mesenchymal cell, unrelated to haematopoietic stem cells, which is capable of in vitro proliferation after as much as 1000 rads of total body irradiation.

Adolescent↗
PubMed1980

Ultrastruct and tartrate-resistant acid phosphatase localization in a T-cell hairy-cell leukemia cell line.

Hairy-cell leukemia is characterized clinically in splenomegaly and pancytopenia and pathologically by the proliferation in hematopoietic tissue of cells containing the tartrate-resistant isozyme 5 of acid phosphatase. We have described a patient with a T-lymphocyte variant of this disease. A permanent cell line obtained from the spleen of this patient has the biological and enzymatic characteristics of the fresh leukemic cells. We have used this line to study the surface morphology, ultrastructure, and ultrastructural localization of acid phosphatase in defined T-lymphoid hairy cells. The surface of the cells of the permanent line was smooth but many hair-like projections appeared after exposure to phytohemagglutinin (PHA). There was little acid phosphatase reaction produce visualized when beta-glycerophosphate was used as a substrate. With sodium haphthol AS-BI phosphoric acid heavy deposits were seen in the perinuclear membrane, mitochondria, and rough endoplasmic reticulum. Exposure to PHA and pokeweed mitogen resulted in increased reaction product, suggesting increased enzyme synthesis. Tartrate-resistant acid phosphatase was localized in the same organelles.

Acid Phosphatase↗