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Biomedical subjects

S Murphy

Publications and source records attributed to S Murphy.

At least 469 records · Page 26Linked to original sources

Use of mini-microaggregated albumin to study reticuloendothelial system (RES) function in C. parvum-treated animals.

Mini-microaggregated albumin colloid (particle size less than 80 A) and microaggregated albumin colloid (particle size 500-1000 A) made from human serum albumin were conjugated with 99mtechnetium and used to study reticuloendothelial system (RES) function in animals treated intravenously with C. parvum. The uptake in blood, liver and spleen were studied in untreated mice and in mice at various times after treatment with 150 or 300 micrograms of C. parvum. The blood clearance of these materials was studied in rabbits before and at various times after treatment with 0.5 mg/kg of C. parvum. In mice, 80 A-microaggregated albumin was cleared significantly faster from the blood and localized to a greater extent in the liver and spleen after C. parvum treatment. There was a positive correlation between the increased organ weight induced by C. parvum and the accelerated clearance of 80 A-microaggregated albumin. The 80 A-microaggregated albumin was also cleared more rapidly from the blood of rabbits after C. parvum treatment. These studies suggest that 80 A-microaggregated albumin labeled with 99mTc is a useful tool for study of RES function in animals and because of its relatively long t 1/2 may also be useful for studies of human RES function.

Animals↗

Developmental changes in polypeptide composition of, and precursor incorporation into, cellular and subcellular fractions of rat cerebral cortex.

Neuronal-enriched and glial-enriched fractions from rat cerebral cortex at 2, 5, 9, 14 and 23 days postnatally, and subcellular fractions from 2, 14 and 46 day old rat were prepared. The polypeptide composition of all fractions was analysed by sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis and quantified by densitometry. Fifty-nine polypeptides (mol. wts., 13,200-251,000) were resolved in the cell fractions of which the majority remained unchanged throughout postnatal development. Three polypeptides (mol. wts., 102,000, 56,000, 53,700) were found to increase in amount developmentally in both cellular fractions, the latter two showing a peak in relative amount on day 14 and a subsequent decline. Three polypeptides (mol. wts., 47,000, 28,200, 17,400) were found to be common to the glial-enriched fraction as well as the myelin fraction, and all showed a developmental increase. The neuronal-enriched fraction was found to be enriched in five polypeptides of which one (mol. wt., 51,900) showed a developmental increase after ten days postnatally, the others (mol. wts., 178,700, 142,000, 109,000, 24,000) showing a decrease. In vitro incorporation of [35S]-methionine into the glial-enriched fraction was carried out, and a developmental decline was observed in the labelling of a polypeptide of 42,000 mol. wt.

Aging↗

Cyclic AMP in female mouse brain is altered by the adrenocorticotropic hormone(4-9) analogue organon 2766.

Cyclic AMP content was determined in 12 brain regions of young adult female mice at 30 min and at 24 h following an intraperitoneal injection of the tri-substituted adrenocorticotropic hormone(4-9) [ACTH(4-9)] analogue Organon 2766 [ORG 2766]. Animals were killed by focused 3.5 kW microwave radiation applied for 350 ms. Unlike previously reported responses in male mice, at 30 min post-injection there were no detectable differences in cyclic AMP content between the placebo and ORG 2766-treated animals. By contrast, 24 h after injection, the content of cyclic AMP was changed significantly in 8 of the 12 brain regions examined: medulla-pons, septal area, thalamus, hypothalamus, hippocampus, olfactory bulb, and parietal and occipital cortices. In most of the regions examined, differences consisted of 50% or greater reductions of tissue cyclic AMP content. The changes were unrelated to the estrus cycle of these animals.

Adrenocorticotropic Hormone↗

Flow cytometry analysis of lung cells from normal and acid-treated rabbits.

Lavaged lung cells from normal rabbits and rabbits given hydrochloric acid intratracheally were analyzed using flow cytometry techniques. The rabbit alveolar macrophage was characterized as a cell with relatively high light scatter and high intrinsic autofluorescence compared with the lung neutrophil with its lower light scatter and autofluorescence. The flow cytometry characteristics of these 2 cell populations were confirmed with light microscopy after cell sorting. A flow cytometry analysis of alveolar macrophage phagocytosis using fluorescent latex particles was applied to normal rabbit alveolar macrophages. These studies showed that flow cytometry can be used to study the morphologic features and function of rabbit lavage lung cell populations and may be ultimately useful in the analysis of human lung cells.

Animals↗

Thrombocytopenia with decreased megakaryocytes. Evaluation and prognosis.

The presenting clinical pictures and courses of seven patients with thrombocytopenia, decreased megakaryocytes in the marrow, and minimal changes in other hematopoietic cell lines are described. Little information exists in the literature on such patients. Initial bone marrow aspiration and biopsy in all patients showed decreased megakaryocytes with an otherwise normal marrow. Erythrocyte mean corpuscular volume was elevated in five of seven patients. Bone marrow karyotypes of six of the seven patients were normal. Chromium-51 platelet survival studies with platelet sizing, done in five of the seven patients, showed normal results. In two patients the course progressed to aplastic anemia. One of these died 9 months after presentation, and one responded dramatically to lithium. One patient developed preleukemia and died. The other four patients have remained thrombocytopenic but clinically stable. No useful therapy was identified. The differential diagnosis of such patients should include idiopathic thrombocytopenic purpura with misinterpretation of morphologic findings, hereditary and acquired aplastic anemia, preleukemia, and systemic lupus erythematosus.

Adult↗

Evidence that essential thrombocythemia is a clonal disorder with origin in a multipotent stem cell.

Essential thrombocythemia is characterized by proliferation of hematopoietic tissue predominantly involving megakaryocytes and resulting in marked thrombocytosis. The disorder has some clinical and laboratory features that resemble those seen in the clonal multipotent stem cell disorders chronic myelogenous leukemia, polycythemia vera, and agnogenic myeloid metaplasia. It has been argued that essential thrombocythemia should be classified together with those disorders as a myeloproliferative syndrome. However, without knowledge of the numbers and types of cells that are involved in essential thrombocythemia, this suggestion remains speculative. Three patients with thrombocytosis were studied. The diagnosis of essential thrombocythemia was considered to be firm in two patients and probable in the third one. The X-linked glucose-6-phosphate dehydrogenase locus was used as a cell marker. Whereas both A and B types of glucose-6-phosphate dehydrogenase were found in nonhematopoietic tissues, only a single-enzyme type was found in the granulocytes, red cells, and platelets from each patient. These data indicate that the disorders in these three patients are clonal and involve multipotent stem cells.

Adult↗

Acquired granular pool defect in stored platelets.

Platelets stored as concentrates (PC) for 72 h at 22 degrees C develop a functional defect. Alterations in adenine nucleotides of platelets have been shown to affect platelet function. Adenine nucleotide content of platelets was measured before and after storage and a decrease of 27.1 /+- 1.7% (mean /+- SE) in ATP and 39.1 /+- 2.6% in ADP were found in 34 PC stored with final volume of 50 ml. In 11 PC with 30 ml volume. ATP and ADP decreased by 39.4 /+- 3.2% and 49.4 /+- 2.1%, respectively. The mean ATP to ADP ratio of stored platelets was significantly higher than of fresh platelets in both groups, suggesting a relatively greater decrease in granular than metabolic pool nucleotides. Levels of low affinity platelet factor 4 measured by radioimmunoassay in plasma from 0.86 /+- 0.08 microgram/ml in the fresh PC to 8.59 /+- 0.39 microgram/ml in stored PC, indicating a concomitant alpha-granular secretion. Labeling of metabolic pool with 14C-adenine revealed a mean decrease in the adenylate energy charge of 2.0 /+- 0.4% in 12 of 16 stored PC, with a lower ATP and higher hypoxanthine labeling in stored as compared to fresh platelets. These observations suggest that stored platelets develop an acquired defect in both dense and alpha granules and in their ability to maintain ATP homeostasis.

Adenosine Diphosphate↗

Changes in serotonin receptors in different brain regions after light exposure of dark-reared rats.

Male rats dark-reared from birth until 50 days of age and then exposed to light for 3 h show significant increases in specific [3H]serotonin (5-[3H]HT) binding to P2 membranes from visual and motor cortex and superior colliculus (25, 65 and 23% respectively) as compared with normal and dark-reared littermates. These increases are transient and return to normal levels after 7 days. The role of 5-HT as a transmitter in the visual system is discussed.

Animals↗

The effect of experimental acid aspiration on alveolar macrophage function in rabbits.

The effect of aspirated hydrochloric acid (HCl) on alveolar macrophage function was investigated in a rabbit model. Lung cells were obtained by bronchoalveolar lavage 4 h after an intratracheal injection of HCl. The intratracheal administration of HCl significantly increased (p < 0.005) the number of neutrophils recovered at lavage. Alveolar marcophage adherence to glass was significantly decreased (p < 0.001) in the HCl-treated animals compared with that of the control animals. Alveolar macrophage phagocytosis was not altered, and there was no effect on macrophage migration through micropore filters. In vitro studies showed that incubation of alveolar macrophages from normal rabbits in cell-free supernatants from HCl-treated rabbit lavage significantly decreased (p < 0.01) alveolar macrophage adherence to glass. In vitro incubation of alveolar macrophages from normal rabbits with rabbit peritoneal neutrophils significantly decreased (p < 0.05) adherence to glass. To investigate the effects of corticosteroid treatment, acid-injured rabbits were given 0.5 mg/kg of dexamethasone intravenously within 5 min. Alveolar macrophages from the steroid-treated animals showed a partial, but significant (p < 0.005), reversal of the acid-induced adherence defect. We concluded that acid aspiration is associated with an influx of neutrophils into the alveolar space, and decreased alveolar macrophage adherence to glass. The adherence defect was related to a factor or factors present in lavage fluid and to the presence of activated neutrophils. Corticosteriod treatment partially reversed the adherence defect.

Adhesiveness↗

Polycythemia vera. Physical separation of normal and neoplastic committed granulocyte-macrophage progenitors.

In previous studies of two patients with polycythemia vera (PV) who were heterozygous at the X-linked locus for glucose-6-phosphate dehydrogenase (G6PD), only A type enzyme was found in nonlymphoid blood cells. However, some erythroid and granulocytic colonies grown in vitro were type B and therefore arose from presumably normal progenitors. One patient had enough type B colonies (8%) that studies of the physical characteristics of normal and PV clonal colony-forming cells could be undertaken. When marrow cells were separated by velocity sedimentation at unit gravity, most PV clonal granulocyte-macrophage progenitors (CFU-C) (type A G6PD) sedimented between 6.4 and 7.2 mm/h, whereas most residual normal, type B CFU-C sedimented less than or equal to 5.9 mm/h (P = 0.04)., When blood cells were separated over a discontinuous buoyant density gradient, PV clonal CFU-C equilibrated at densities < 1.065 g/ml, whereas residual normal CFU-C were found greater than or equal to 1.065 g/ml (P < 0.01). PV clonal and residual normal erythroid burst-forming progenitors were not separable by either method. Thus PV clonal CFU-C are larger and less dense cells than are residual normal CFU-C.

Erythrocytes↗

Polycythemia vera. Further in vitro studies of hematopoietic regulation.

Further in vitro studies of hematopoietic regulation were carried out in two patients with polycythemia vera who were also heterozygotes (Gd(B)/Gd(A)) for glucose-6-phosphate-dehydrogenase (G-6-PD). While only G-6-PD type A was detectable in circulating erythrocytes, granulocytes and platelets, cultures of peripheral blood and marrow from one patient revealed a substantial number of G-6-PD type B erythroid burst-forming units (BFU-E) and granulocyte/macrophage colony-forming units. Detailed analysis demonstrated: (a) where detectable, normal BFU-E and granulocyte/macrophage colony-forming units were found with similar frequencies; (b) the same frequencies for normal progenitors characterized cultures of peripheral blood and marrow; (c) inhibition of normal erythroid differentiation between BFU-E and the more mature erythroid colony-forming unit; (d) a decline in the prevalence of normal colony-forming units with time, suggesting that disease progression is associated with further suppression of normal hematopoiesis by products of the abnormal clone.

Bone Marrow Cells↗