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Biomedical subjects

W McDonough

Publications and source records attributed to W McDonough.

4 recordsLinked to original sources

Altered gene expression in human astrocytoma cells selected for migration: I. Thromboxane synthase.

Human glioma cells from a long-term cell line were selected for their ability to migrate on a glioma-derived extracellular matrix. When tested over 28 serial passages, the migration-selected strain showed a genetically stable, enhanced migration rate compared with the parental cells. Proliferation studies demonstrated that the growth rate of migration-selected cells was slightly arrested. Both the selected strain and the parental culture showed anchorage-independent growth in soft agarose and were tumorigenic in athymic mice. Using molecular genetic strategies' display to isolate genes expressed differentially between the 2 populations, a 300-bp sequence homologous to thromboxane synthase was upregulated in the migration-selected cells relative to the parental cells. Expression levels of thromboxane synthase were highly elevated in the migration-selected cells when assessed by RNAse-protection assay and by flow cytometry. Two specific thromboxane synthase inhibitors, Dazmegrel and Furegrelate, reduced the migration rate of the migration-selected cells to a rate equal to or less than the rate exhibited by the parental cells, respectively. The inhibitors effect on the parental cells was inconsequential. These results suggest that aberrations in the regulation of thromboxane synthase expression or activity may influence the motility of human glioma cells.

Animals↗

A randomized, double-blind comparison of donor tolerance of 400 mL, 200 mL, and sham red cell donation.

BACKGROUND: Volume replacement could allow the safe collection of twice the normal amount of red cells in a standard donation. Studies in small numbers of donors have shown that a temporary decrease in red cell mass is well tolerated when donors give twice the usual amount (170-225 mL) of red cells in a standard 405- to 495-mL donation. Sham-donation control groups have not been included in previous studies of increased red cell donation, and perceptions of donation effects could have been biased. STUDY DESIGN AND METHODS: In the study reported here, 17 male and 13 female volunteers were randomly assigned to make a sham donation, 1-unit donation, or 2-unit donation on an automated blood cell separator. Donor tolerance was assessed by ambulatory heart rate monitoring and by a poststudy interview. Hemoglobin, hematocrit, ferritin, serum iron, total iron-binding capacity, red cell 2,3 DPG, and serum erythropoietin were measured before and after donation for comparison of the erythropoietic responses in the three study groups. RESULTS: Red cells collected totaled 206 +/- 10 mL in the 1-unit group and 414 +/- 21 mL in the 2-unit group. Changes in heart rate, systolic blood pressure, and diastolic blood pressure with donation and changes in heart rate recorded by ambulatory monitoring did not differ for the experimental groups. Postdonation changes from baseline values were evaluated on Days 2, 7, and 14. Changes in hemoglobin were significantly different between groups (p < 0.017) in all postdonation tests. There were differences between groups in erythropoietin response, red cell 2,3 DPG, ferritin levels, and hemoglobin synthesis. Hemoglobin synthesis and mean changes in 2,3 DPG, erythropoietin, ferritin, and postdonation hemoglobin were greater in the 2-unit group than in the 1-unit group. CONCLUSION: Donor tolerance of red cell donations of 414 +/- 21 mL, a volume of red cells twice that in a standard 450-mL blood donation, does not differ from donor tolerance of standard or sham donations. Physiologic adjustments and the hematopoietic response to reduced red cell mass were greater in the 2-unit group, but the donation of 1 unit or 2 units did not cause detectable symptoms of reduced oxygen-carrying capacity.

Blood Donors↗

In vitro evaluation of a new dual screen microaggregate filter.

We compared a new second generation 40/150 mum dual screen microaggregate filter with a currently available 40 mum screen microaggregate filter. The evaluation included comparison of filter flow rate, capacity, degree of microaggregate removal, degree of leukocyte removal, and extent of filtration-induced hemolysis. We also studied the effect of both devices on filtration of stored platelet concentrates. The 40/150 mum dual screen microaggregate filter showed results comparable to that of the control screen filter following filtration of various types of units of red blood cells as well as units of stored platelet concentrates. Importantly, mean flow rates with the new 40/150 mum filter of 45 g/min after gravity filtration of 1600 mL of blood, make the filter suitable for use in trauma or other massive transfusion settings. We conclude that this new second generation microaggregate filter is suitable for use in clinical transfusion practice.

Evaluation Studies as Topic↗