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S H Russell

Publications and source records attributed to S H Russell.

22 records · Page 2Linked to original sources

Influence of human serum components on measurement of erythropoietin biological activity in vitro. Studies with a rabbit bone marrow bioassay procedure.

The influence of human serum components during in vitro determination of erythropoietin biological activity has been examined in a modified in vitro bioassay procedure utilising rabbit bone marrow as the erythropoietin-responsive tissue. The number of erythroblasts present after 5 d in suspension culture provided a measure of erythropoietin biological activity with a degree of sensitivity equivalent to that provided by estimation of 59Fe incorporation into haem, but possessed the advantage of lacking the susceptibility of the latter method to the level of human serum transferrin saturation. Erythropoietic stimulation was blocked by 10% human serum unless all sera incorporated into the bioassay was previously heated at 56 degrees C. Human serum under the latter conditions was shown to contain material which stimulated erythropoiesis, but which differed in its mode of action from erythropoietin in that it operated by amplifying the response to erythropoietin. Correction for these effects substantially altered interpretation of erythropoietic stimulatory activity of human serum to yield values in keeping with those reported for in vivo bioassay. These findings illustrate the need to clarify the role of human serum components which modify the action of erythropoietin under culture conditions, in view of their potential contribution to discrepancies between values obtained by different bioassay procedures.

Anemia↗

Granulocyte/macrophage-, megakaryocyte-, eosinophil- and erythroid-colony-stimulating factors produced by mouse spleen cells.

The formation of mature haemopoietic cells is controlled by hormones that specifically stimulate the progenitor cells of the granulocyte/macrophage, eosinophil, megakaryocyte and erythroid pathways. PWMSC medium (pokeweed-mitogen-stimulated spleen-cell-conditioned medium) is known to contain the biological activities that control the clonal proliferation of these four progenitor cells in vitro in semi-solid agar cultures. In this study the molecular properties of these biological activities were characterized, and all four colony-stimulating factors appear to be associated with glycoproteins. These factors were precipitated between 50 and 80%-satd. (NH(4))(2)SO(4) and could be concentrated by ultrafiltration over a 10000-mol.wt.-cut-off hollow-fibre membrane. Megakaryocyte- and erythroid-colony-stimulating factors were lost when the conditioned medium was dialysed at low ionic strength (<0.03m). Neither asialo- nor sialo-erythropoietin was detectable in concentrated PWMSC medium or in the fractions purified from it by gel filtration on Sephadex G-150. The factors bound to concanavalin A-Sepharose were eluted with alpha-methyl-d-glucopyranoside (0.10m). Analysis by gel filtration on Sephadex G-150 indicated that the apparent molecular-weight distributions of all colony-stimulating factors were identical (37000). Treatment with neuraminidase did not alter the biological activities of any of these factors, but when the molecular weights were analysed, after neuraminidase treatment, on Sepharose CL-6B in the presence of guanidine hydrochloride (6m) all were eluted with a mol.wt. of 24000. Although the apparent molecular weights of the different factors were identical, charge differences were detectable by isoelectric focusing on thin-layer granulated gels. There appeared to be considerable charge heterogeneity associated with each factor, as all were focused over 2-4 pH units. The maximum activity of the granulocyte/macrophage-colony-stimulating factor on isoelectric focusing was at pH4.8, whereas the maximum activity for the eosinophil-colony-stimulating factor was at pH5.8. The erythroid- and megakaryocyte-colony-stimulating activities were detected in the pH ranges 4.8-5.8 and 4.6-7.1 respectively. Chromatographic differences between the granulocyte/macrophage- and eosinophil-colony-stimulating factors were also detected by hydrophobic chromatography at low ionic strength (0.15m-NaCl) on Cibacron Blue-Sepharose and at high ionic strength [2m-(NH(4))(2)SO(4)] on phenyl-Sepharose. Eosinophil-colony-stimulating factor bound more strongly than the other factors to both matrices. The megakaryocyte- and erythroid-colony-stimulating activities were always associated with those for granulocytes/macrophages and eosinophils. Preparations highly enriched for eosinophil-colony-stimulating factor were also obtained by DEAE-cellulose chromatography. An overall purification of 100-fold for all of the factors was achieved with the present techniques, and, although differences were observed, only granulocyte/macrophage-stimulating factors and a small proportion of the eosinophil-stimulating factors could be completely separated from the others. Our results are consistent with the existence of separable factors for granulocyte/macrophage and eosinophil stimulation, but the megakaryocyte- and erythroid-stimulating activities were always associated with the granulocyte/macrophage- and eosinophil-stimulating activities. Thus there may be one molecule that is able to stimulate all four colony types or four very similar molecules that are difficult to separate.

Animals↗

Results of a two-year health education campaign on dietary behavior. The Stanford Three Community Study.

A two-year, bilingual mass-media health education campaign was carried out in two communities with a third serving as control. In one of the two treated communities, personal couseling of high risk individuals ("intensive instruction") took place. Dietary behavior, before and after the campaigns, was assessed using a dietary questionnaire which estimated the average daily consumption by participants of cholesterol, saturated fat, and polyunsaturated fat. Both intensive instruction and the mass-media campaigns led to significant reductions (20-40%) in cholesterol and saturated fat consumption in both men and women, with intensively instructed men tending to outperform men exposed to mass-media alone. In general, the improvements in the treated communities were maintained over the two years of the study, whereas the initial small drops in the control community at the end of the first year were followed by recidivism during the second year. Polyunsaturated fat consumption fell slightly in all three communities so that increases in P/S ratios in the two treated communities were of only modest degree. Mean changes in plasma cholesterol concentration for the various cohorts under study were higly correlated with those which would have been predicted on the basis of the self-reported changes in dietary behavior. The results indicate that mass-media health education campaigns can lead to significant changes in dietary practices in the general population with potentially important public health implications.

Adult↗