Search PubMed⌕ Search

Biomedical subjects

B O'Rourke

Publications and source records attributed to B O'Rourke.

59 records · Page 4Linked to original sources
PubMed1987

Effects of recombinant IL-3, GM-CSF, and G-CSF on proliferation of leukemic clonogenic cells in short-term and long-term cultures.

To further define the growth factors required for the in vitro proliferation of acute myeloblastic leukemic (AML) cells, we have compared the ability of recombinant interleukin-3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF), and granulocyte colony stimulating factor (G-CSF) to support growth of AML colony forming cells (AML-CFU). IL-3, GM-CSF, and G-CSF are active as single growth factors in short-term colony cultures and have additive effects when used in combination in some cases. The effects of these CSFs on the proliferation of AML cells in long-term-cell-suspension cultures were also investigated. These cultures provide an estimate of the "self-renewal" capacity and long-term proliferation potential of AML cells. There was considerably heterogeneity with regard to the effects of individual growth factors, but in general, IL-3, GM-CSF, and G-CSF promoted self-renewal of AML cells, and combinations tended to be more effective in supporting long-term survival of AML-CFU. There was evidence of gradual differentiation, but this was evident in control cells and did not appear to be accelerated by CSF treatment. These results of short-term and long-term cultures indicate that each of the CSFs tested can be used by AML cells to support proliferation. The lack of evidence that the CSFs enhance in vitro differentiation does not suggest they will be valuable as therapeutic differentiation agents.

Cell Division↗
PubMed1986

Altered phospholipid metabolism in pressure-overload hypertrophied hearts.

The content and fatty acyl composition of phospholipids were examined in pressure-overload hypertrophied hearts. Cardiac hypertrophy was induced in rats by abdominal aortic constriction. Twenty-one days postconstriction the content of myocardial phosphatidylcholine (PC), sphingomyelin, and phosphatidylinositol (PI) was significantly elevated by 10, 10, and 20%, respectively. The essential fatty acid, linoleic acid, was markedly reduced in PC, phosphatidylethanolamine (PE), PI, and cardiolipin (CL) of hypertrophied hearts. The associated changes in fatty acyl composition were specific for the individual phospholipid class as evidenced by a significant elevation of palmitic acid in PC, docosahexaenoic acid in PE and oleic acid in CL. Alterations in fatty acyl composition of phospholipids were associated with no change in the composition of cardiac triglycerides, cardiac free fatty acids or serum lipids. The fatty acyl composition of phospholipids was also altered in pressure-overload hypertrophied hearts of cats, as evidenced by a reduction of linoleic acid and an elevation of arachidonic acid in total phospholipids. These findings demonstrate that changes in phospholipid metabolism occur in the pressure-overloaded mammalian heart. Such alterations may contribute to altered membrane function in the hypertrophied myocardium.

Animals↗
PubMed1985

Altered carnitine metabolism in spontaneously hypertensive rats.

Carnitine metabolism was examined in spontaneously hypertensive rats (SHR). Carnitine levels were elevated by 25% in hypertrophied hearts of 10- and 15-wk-old SHR when compared with Wistar-Kyoto (WKy) controls. This elevation was associated with a greater than 25% increase in total serum carnitine. The elevated serum carnitine does not appear to be due to increased mobilization from skeletal muscle because carnitine levels were elevated by 25% in gastrocnemius and diaphragm of SHR. Elevated serum carnitine is also not a result of reduced urinary excretion because daily urinary carnitine output was increased by 150% in SHR. These findings suggest that the most likely mechanism for increased serum carnitine is increased carnitine synthesis by the liver. The changes in carnitine metabolism in SHR appear to occur between 5 and 10 wk of age, because the carnitine levels in serum and organs were comparable in 5-wk-old WKy and SHR. The observed alterations in tissue and serum carnitine levels may result in altered fatty acid utilization in SHR.

Animals↗
PubMedDate not supplied

Cell-type specificity of preconditioning in an in vitro model.

We investigated whether preconditioning could protect several cultured cell lines, to determine whether the protection is specific for cells derived from different myogenic and non-myogenic sources. Ischemia was simulated by centrifugation of cells into a pellet, and cell viability was determined by hypotonic trypan blue solution. Preconditioning was produced by brief exposures to either glucose-free solution or metabolic inhibition. Freshly isolated rabbit ventricular myocytes were studied to confirm that preconditioning occurs in this model. We then compared these results to those in several cultured cell lines, including HEK 293 cells derived from human embryonic kidney, HIT-T15 cells from Syrian hamster pancreatic islets, and C2C12 cells from mouse skeletal muscle. In the latter cell line, we also determined whether differentiation alters preconditioning. Preconditioning protected rabbit ventricular myocytes: the percentage of dead cells was decreased from 36.8 +/- 4.7% in the control group to 23.0 +/- 5.2% in the preconditioned group after 60 min and from 50.7 +/- 2.1% in the control group to 25.5 +/- 4.5% in the preconditioned group after 120 min ischemia (p < 0.02). In contrast, there was no protection from preconditioning in HEK 293 cells or HIT-T15 cells. Preconditioning did not protect C2C12 myoblasts either. Interestingly, after C2C12 myoblasts had differentiated into myotubes (induced by exposing the cells to low-serum medium), they could then be protected by preconditioning (46.3 +/- 3.6% in the control group vs 26.0 +/- 2.7% in the preconditioned group after 60 min and 67.4 +/- 3.6% in the control group vs 46.0 +/- 4.6% in the preconditioned group after 120 min ischemia; p < 0.05). In conclusion, protection from preconditioning is cell-type specific. The presence of endogenous KATP channels (which are plentiful in HIT-T15 cells) is insufficient to enable preconditioning of the cell. Among the various cell types studied, only differentiated muscle cells (rabbit ventricular myocytes and C2C12 myotubes) exhibited preconditioning.

Animals↗