Publications by authors named "M L McGeady"

Background: Major hemorrhage is a significant cause of mortality and morbidity around the world. There is currently no consensus on the best empirical transfusion strategy. The current National Institute for Clinical Excellence (NICE) guidelines suggest a ratio of 1:1 of red blood cells and plasma.

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Transforming growth factor alpha (TGF alpha) is one growth factor that has been circumstantially implicated in regulating the autocrine growth of breast cancer cells. Expression of TGF alpha can be modulated by activated cellular protooncogenes such as ras and by estrogens. For example, the epidermal growth factor (EGF)-responsive normal NOG-8 mouse and human MCF-10A mammary epithelial cell lines can be transformed with either a point-mutated c-Ha-ras protooncogene or with a normal or point-mutated c-neu (erbB-2) protooncogene.

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MCF-10A cells are a spontaneously immortalized normal human mammary epithelial cell line. MCF-10A cells were transfected with two expression vector plasmids containing either a human point-mutated c-Ha-ras protooncogene or the rat c-neu protooncogene. c-Ha-ras-transfected MCF-10A cells grow as colonies in soft agar, exhibit a 3- to 4-fold increase in their growth rate in serum-free medium, and show a reduced mitogenic response to exogenous epidermal growth factor (EGF) or transforming growth factor-alpha (TGF alpha) as compared to MCF-10A cells.

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A new class of nontransformed revertant cells has been isolated from the ras-transformed cell line DT using cis-4-hydroxy-L-proline (CHP) as a selective agent. The new revertants, CHP 9CJ and CHP CB4, each contain two copies of the v-Ki-ras gene, elevated levels of phosphorylated p21ras protein, and rescuable transforming virus, indicating that the revertant phenotype observed in these cells does not result from inactivation of v-Ki-ras or inhibition of its expression. Both CHP 9CJ and CHP CB4 revertants show a greatly reduced ability to form colonies in soft agar and to produce tumors in syngeneic mice.

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A retroviral vector system for the expression of exogenous genes under the control of an inducible promoter was developed. By utilizing this system, the cDNA for human transforming growth factor beta 1 (TGF-beta 1) was inserted into a retroviral vector under the control of an internal mouse metallothionein promoter and introduced via infection into normal rat kidney fibroblasts (NRK-49F) and epithelial cells (NRK-52E), Chinese hamster ovary cells (CHO), and the human monocytic cell line U937. Control of TGF-beta 1 expression, achieved by Cd2+ induction of vector-encoded TGF-beta 1 mRNA, was cell line specific and resulted in a concomitant increase in neutralizable TGF-beta 1 production by the cells.

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