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Biomedical subjects

D G Nathan

Publications and source records attributed to D G Nathan.

288 records · Page 16Linked to original sources
PubMed1968

Stages in the incorporation of fatty acids into red blood cells.

Mature human erythrocytes were incubated with (14)C-labeled palmitic acid bound to crystalline human albumin. Energy-dependent incorporation of the labeled palmitic acid into cell membrane phospholipids occurred, and various stages in this incorporation were defined. Initially the palmitic acid was rapidy transferred from the albumin to a "superficial" membrane pool of free fatty acid (F-1), which was removable when the cells were washed with defatted albumin. This process was independent of red cell metabolism. The labeled fatty acid then passed into a second "deeper" membrane pool of free fatty acids (F-2), which was not extractable with albumin. This process was energy-dependent and proceeded at a slower rate than the initial transfer from albumin to F-1. Ultimately the labeled fatty acid was incorporated into phosphatides (PL). This process also was dependent upon cellular metabolism. The kinetics of pulse label studies suggest that the processes observed were sequential and that precursor-product relationships exist between the F-1 and F-2 pools and the F-2 and PL pools. [Formula: see text] From the size and specific activities of these pools, calculations of the extent of phospholipid turnover were made. An approximate figure of 2% /hr or 30 nmoles/ml of packed red blood cells per hr was obtained. The figure was further calculated to represent an energy cost to the red blood cell of approximately 5% of the energy available from glycolysis.

Cell Membrane Permeability↗
PubMed1967

Leukocyte oxidase: defective activity in chronic granulomatous disease.

The intact leukocytes of two children with chronic granulomatous disease fail to reduce nitroblue tetrazolium during phagocytosis. This is due to defective operation of an oxidase of reduced nicotinamide adenine dinucleotide that is insensitive to cyanide and that indirectly stimulates the oxidation of glucose-6-phosphate in leukocytes. Such leukocytes undergo no increase in oxygen consumption or in activity of the hexose monophosphate shunt during phagocytosis, although lactate production is normal. The addition of nitroblue tetrazolium to a leukocyte suspension appears to provide a sensitive diagnostic screening test for this disease.

Carbon Isotopes↗
PubMedDate not supplied

Introduction of new genetic material into pluripotent haematopoietic stem cells of the mouse.

An infectious retrovirus vector has been used to transfer a bacterial gene encoding resistance to the neomycin analogue G418 into pluripotent haematopoietic stem cells present in explanted murine bone marrow tissue. Subsequent transplantation of the cells into lethally irradiated mice results in engraftment of the animals with donor haematopoietic tissue containing the bacterial gene. This approach affords an efficient and rapid means of re-introducing genetically modified tissue into intact organisms and provides a system whereby the expression and regulation of cloned genes can be followed within the context of a well characterized developmental programme.

Animals↗
PubMedDate not supplied

T cell and monocyte-derived burst-promoting activity directly act on erythroid progenitor cells.

While the terminal stages of erythroid differentiation are regulated by the hormone erythropoietin, the early stages of proliferation and differentiation of immature erythroid progenitor cells also depend on cellular factors functionally defined as burst-promoting activity (BPA). Thus, in vitro there is suboptimal development of primitive erythroid progenitor cells (burst-forming units--erythroid, BFU-E) into colonies unless a source of BPA is added. It has been demonstrated that T cells and monocytes produce BPA. Monocytes may represent the main source of BPA and the major role of T cells may be to augment BPA production by monocytes. Irradiated bone marrow cells, which contain T cells, monocytes and other BPA-producing cells, also promote BFU-E colony formation. As these studies used crude BFU-E populations as target cells, it was not possible to define which of the accessory cell products act directly on the progenitor cell. Here we have used a panel of monoclonal antibodies to purify BFU-E from peripheral blood. We demonstrate that BPA produced by both a monocyte and a T-cell line acts directly on the erythroid progenitor cell and can support colony formation by single BFU-E.

Antibodies, Monoclonal↗
PubMedDate not supplied

Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSF.

Certain proteins are known to play an important part in the proliferation, differentiation and functional activation of haematopoietic progenitor cells in vitro. These proteins include erythropoietin and various colony-stimulating factors (CSFs), one of which is granulocyte-macrophage colony-stimulating factor (GM-CSF). Recently, both murine and human GM-CSF have been purified to homogeneity and complementary DNAs encoding them have been cloned. Although the in vitro activity of recombinant human GM-CSF has been investigated intensively, little is known about the functional activity of this protein in vivo. There is strong evidence that colony-stimulating activities produced by various human and murine tumour tissues and cell lines can stimulate granulopoiesis in mice, as can human urinary extracts. A partially purified preparation of human urinary colony-stimulating factor, however, proved only marginally effective in stimulating granulopoiesis in humans. All these studies suffer from the lack of a homogeneous preparation of colony-stimulating factor. It has recently been shown that recombinant murine multi-CSF or interleukin-3 can stimulate haematopoiesis in mice in vivo. Large-scale production of recombinant human GM-CSF now permits us to examine its effects in vivo using a primate model. We find that the continuous infusion of GM-CSF in healthy monkeys rapidly elicits a dramatic leukocytosis and a substantial reticulocytosis. A similar effect has been observed in one pancytopenic, immunodeficient rhesus macaque. These results suggest that GM-CSF could prove useful in several clinical situations.

Animals↗