Biomedical subjects

S Ings

Publications and source records attributed to S Ings.

3 recordsLinked to original sources

PubMed2000

Effect of changes in expression of the amphotropic retroviral receptor PiT-2 on transduction efficiency and viral titer: implications for gene therapy.

The aim of this study was to quantify the impact of amphotropic retroviral receptor (PiT-2) levels on susceptibility to transduction and to determine whether the low level of PiT-2 found on CD34+ hematopoietic cells is within the range likely to compromise gene transfer. Receptor-deficient Chinese hamster ovary (CHO) cells were transfected with a PiT-2 construct that could be induced by the removal of tetracycline. The level of PiT-2 expression measured by virus binding in uninduced and in fully and partially induced transfectants correlated with the efficiency of transduction by an amphotropic retroviral reporter vector. Fully induced CHO-PiT-2 cells gave apparent viral titers similar to NIH 3T3 fibroblasts while addition of tetracycline reduced titers by up to 140-fold. Binding of the same vector preparation to purified CD34+ peripheral blood stem cells (PBSCs) was always less than to uninduced CHO-PiT-2 transfectants even after preincubation in 10-ng/ml concentrations of IL-3, IL-6, and stem cell factor, which increased retroviral binding by an average of 35%. The level of expression of the amphotropic retroviral receptor PiT-2 thus significantly limits transduction efficiency within the range observed in target cells of importance in human gene therapy.

3T3 Cells↗

PubMed2000

Diet therapy--a forgotten art?

This study evaluated paediatric nursing students' knowledge of diet therapy to establish whether it was sufficient to prepare them for practice. A questionnaire sampled 19 1st-year and nine 4th-year students' diet therapy knowledge in relation to chronic renal failure, cystic fibrosis, juvenile diabetes mellitus and liver disease. The knowledge of 1st and 4th-year students was compared and then evaluated against criteria, devised by the researcher to measure whether this knowledge level was sufficient for practice. The Mann-Whitney Utest showed a significant difference between the 1st and 4th-years' diet therapy knowledge. The mean score for overall diet therapy knowledge of 4th-year students was 46 per cent. The results suggest that knowledge of diet therapy is insufficient to prepare nursing students for practice and that this topic needs further emphasis in paediatric nurse education.

Child↗

PubMed1998

Transmigration of CD34+ cells across specialized and nonspecialized endothelium requires prior activation by growth factors and is mediated by PECAM-1 (CD31).

The transmigration of hematopoietic progenitor cells (HPCs) across vascular endothelium is a critical step in the homing of transplanted stem cells, but the molecular basis for this is unknown. We used mobilized peripheral blood CD34(+) selected cells and cultured bone marrow microvascular (BMECs) and human umbilical vein endothelial cells (HUVECs) to investigate the adhesion and transendothelial migration of HPCs. Colony-forming cells (CFCs) in freshly isolated CD34(+) cells showed high levels of adhesion to both forms of endothelium (28% +/- 4% and 38% +/- 6% of granulocyte-macrophage colony-forming cells [GM-CFCs] adhering to HUVECs and BMECs, respectively), but were unable to migrate to any significant extent across either (1.0% +/- 0.3% and 1.1% +/- 0.6% of GM-CFCs migrating across HUVECs and BMECs, respectively). Greater than 95% of peripheral blood CD34(+) cells are in G0/G1 of the cell cycle, but after 48 to 72 hours of stimulation with growth factors (interleukin-3 [IL-3] 12 ng/mL, stem cell factor 10 ng/mL, and IL-6 10 ng/mL), 28% +/- 5% of cells were in S+G2/M. Growth factor stimulation had no effect on the adhesion of mobilized CFCs but resulted in enhanced migration of these cells (9.8% +/- 1.6% and 12. 6% +/- 3.1% of GM-CFCs migrating across HUVECs and BMECs, respectively; P < .01, n = 6). Assessment of cell proliferation by the 3H-thymidine suicide method showed that, whereas 11.7% +/- 3.3% of proliferating CFCs transmigrated across endothelium, only 1.3% +/- 0.3% of nonproliferating CFCs did so (P < .05, n = 5). Transmigration of growth factor-activated CFCs was inhibited by anti-CD18 monoclonal antibody (MoAb; 50% +/- 18% inhibition) and by anti-platelet endothelial cell adhesion molecule-1 (PECAM-1) MoAb (70.8% +/- 7.1% inhibition; P < .05, n = 3). IL-1 stimulation of HUVECs had no significant effect on CD34(+) cell transmigration, but caused marked enhancement of neutrophil migration. Stem cell homing may depend, in part, on the ability of local cytokines to upregulate the transmigratory ability of these cells. The transmigration of HPCs shares at least some molecular pathways with that of mature cells (CD18 and PECAM-1), but is differently affected by endothelial activation.

Antigens, CD34↗