PubMed Health⌕ Search

Biomedical subjects

D W Golde

Publications and source records attributed to D W Golde.

At least 343 records · Page 19Linked to original sources

Occult pulmonary haemorrhage in leukaemia.

Through gleeding into the lung parenchyma is responsible for morbidity and mortality in patients with leukaemia pulmonary haemorrhage is seldom diagnosed during life. We diagnosed occult pulmonary haemorrhage in five leukaemic patients with unexplained infiltrates on chest roetgenograms by examining alveolar macrophages retrieved by bronchopulmonary lavage. Macrophage haemosiderin content was greatly increased in the patients with pulmonary haemorrhage as compared to normal and thrombocytopenic control subjects. Haemoglobin and intact erythrocytes in alveolar macrophages were taken as evidence of recent haemorrhage. Intrapulmonary bleeding may occur often in patients with leukaemia, and bronchopulmonary lavage offers a safe approach to diagnosis and allows for concomitant identification of pulmonary infection.

Autopsy↗

Chronic neutropenia: Response to plasma with high colony-stimulating activity.

A child with repeated infections was immunologically normal but was found to have neutropenia with periodic elevations of the absolute mature polymorphonuclear count at 21-day intervals. Immediately following the PMN rise, bone marrow morphology and in vitro cultures demonstrated a maturation arrest at the myelocyte stage with an increase in proliferative capacity. His cycle was not altered by infusions of normal plasma or by injections of epinephrine or typhoid vaccine. Infusion of 10 ml/kg of "stimulated" plasma from donors reactive to TV, obtained 60 minutes following immunization, resulted in an out-of-phase rise in PMN cells and clinical improvement. In vitro assays, using normal or patient marrow, detected high levels of colony-stimulating activity only in those plasma samples that were effective in the patient. These observations support a role of CSA as a physiologic regulator of granulopoiesis in man.

Agranulocytosis↗

Erythropoietin responsiveness in polycythaemia vera.

A liquid bone marrow culture technique was used to study erythropoiesis in polycythaemia vera. Three patients with the diagnosis of polycythaemia vera treated only by phlebotomy were compared to three healthy volunteers. Erythropoiesis in vitro was assessed by counts of nucleated red cells and 3H-thymidine incorporation into erythroid precursors. Human urinary erythropoietin was found to stimulate erythropoiesis in cultures from the polycythaemia patients as well as normals. The erythropoietin effect was blocked by a rabbit anti-erythropoietin antibody. These results suggest that some erythroid precursor cells maintain an intact erythropoietin response mechanism in polycythaemia vera. They also support clinical studies of this disorder indicating that some regulation by erythropoietin may occur in vivo.

Cell Count↗

Proliferation and maturation of human leukemia cells in liquid culture.

Bone marrow from patients with acute myelogenous leukemia (AML), acute myelomonocytic leukemia (AMML), chronic myelogenous leukemia (CML), preleukemia, and from healthy volunteers was cultured using a recently developed liquid diffusion technique. Differential and viable cell counts and 3H-thymidine labeling indices were performed at intervals up to 30 days. Differentiation was assessed morphologically by light and electron microscopy, histochemically, and by functional tests for phagocytosis and the presence of surface receptors for IgG. Colony-stimulating activity (CSA) was assayed against normal human bone marrow by the agar colony technique. In acute leukemia cultures, viable cell counts usually fell within the normal range. However, most AML cells failed to demonstrate significant maturation in vitro, and did not produce detectable CSA. In AMML cultures, maturation was defective but some differentiated macrophages were observed and the cells produced high concentrations of CSA. Preleukemic cultures demonstrated normal growth but maturation was impaired as evidenced by a high percentage of immature cells during the first 7 days. CML cultures showed abnormally high growth capacity resulting in viable cell counts 2-3 times normal. In the chronic phase of CML, maturation was qualitatively normal and the cells produced CSA. With the onset of blast transformation, maturation became abnormal but growth remained high. These studies support a concept of AML as a primary defect in cellular maturation and of CML as a primary abnormality of proliferation. The production of CSA by neoplastic cells relates to the degree of monocyte-macrophage differentiation within the leukemic population. Human preleukemia is characterized by a failure of normal maturation in vitro.

Bone Marrow↗

Occult pulmonary hemorrhage in anticoagulated patients.

Evidence for severe intrapulmonary bleeding was obtained in 3 anticoagulated patients who presented with pulmonary infiltrates. The diagnosis of pulmonary hemorrhage was based on findings of markedly elevated quantities of stainable hemosiderin and hemoglobin in alveolar macrophages retrieved by bronchopulmonary lavage. In 2 of the patients, roentgenographic abnormalities regressed after anticoagulation was reversed. The third patient died and massive bilateral pulmonary hemorrhage was found at autopsy. The syndrome of occult pulmonary hemorrhage was characterized clinically by dyspnea, unexplained acute anemia, and infiltrates with an alveolar pattern on chest roentgenogram. Hemoptysis was conspicuously absent. Bronchopulmonary lavage and quantification of alveolar macrophage hemosiderin content may be useful in identifying intrapulmonary bleeding occurring in an otherwise occult manner. Recognition of pulmonary hemorrage in anticoagulated patients is important because reversal of anticoagulation can be life saving.

Adult↗

Thymus-dependent lymphocytes in human bone marrow.

Human bone marrow is known to contain significant numbers of bursa-dependent lymphocytes. The presence of thymus-dependent (T) cells is controversial. Bone marrow cells obtained from healthy volunteers was fractionated by density centrifugation. A lymphocte-enriched subpopulation was shown to be reactive to alloantigens in mixed lymphocyte culture and to contain substantial numbers of T lymphocytes. The T lymphocytes were detected by cell surface markers (rosette formation with sheep RBC) and by response to the mitogens phytohemagglutinin and concanavalin A. Bone marrow T cells exhibited functional characteristics quantitatively different from peripheral blood T cells, suggesting that they may represent a particular subpopulation of T cells. The lymphocyte-enriched fraction additionally contained committed granulopoietic stem cells capable of colony formation in semisolid gel. The presence of T cells in human bone marrow is consistent with findings in other mammals and may explain the high incidence of graft versus host disease in bone marrow transplant recipients.

Adult↗

Endotoxin-induced release of colony-stimulating activity in man.

Six healthy adult volunteers were injected intravenously with Pseudomonas endotoxin (Piromen) to determine effects on serum colony-stimulating activity (CSA). Serum was assayed with a double-layer agar cloning technique using normal human bone marrow as the target cell preparation. A marked increase in serum CSA was noted after endotoxin administration lasting up to 180 min. The colonies formed in response to postendotoxin serum were smaller than those seen with leukocyte feeder layers but were otherwise morphologically normal. These studies suggest that granulopoietic humoral factors may be modulated in man by endotoxin administration.

Adult↗

Pathogenesis of one variant of sea-blue histiocytosis.

Hematopoietic cells from three siblings of a family with sea-blue histiocytosis were studied using in vitro cell culture techniques, histochemistry, and electron microscopy. Sphingomyelinase activities in cultured fibroblasts derived from these patients averaged 18 per cent of control levels. Ultrastructural examination of the sea-blue histiocytes showed numerous acid phosphatase-containing inclusions with closely packed, concentrically arranged, membrane-like lamellae with a periodicity of approximately 45 A. The inclusions are thought to result from the spatial orientation of complex lipid molecules and water. These structures are consistent with secondary lysosomes and are similar to those seen in some cases of adult Niemann-Pick disease and other cases of sea-blue histiocytosis. Extraction of lipid did not alter the blue-staining characteristics of the histiocytes. Sea-blue histiocytes were seen in liquid bone marrow cultures but did not proliferate, suggesting that the mature sea-blue macrophage is a terminal cell. We propose that partial sphingomyelinase deficiency may be one cause of sea-blud histiocytosis.

Bone Marrow↗