Biomedical subjects

S J Ralph

Publications and source records attributed to S J Ralph.

22 records · Page 2Linked to original sources

PubMed1984

Binding of monoclonal antibodies that inhibit spleen colony formation to leukemic cell lines.

Clonogenic tumor cells and normal stem cells share the property of extensive proliferative potential. Normal stem cells are under stringent growth restraint and respond to appropriate differentiation signals, whereas tumor stem cells have lost the ability to respond normally to these controls. In an attempt to define cell surface molecules involved in the control of hemopoietic cell proliferation and differentiation, we have produced 5 monoclonal antibodies against antigens held in common between hemopoietic stem cells and the Abelson virus-induced pre-B-lymphoma cells from which they were derived. Four of these monoclonal antibodies produced greater than 90% reduction of spleen colony-forming cells, whereas the other bound to a subpopulation (60 to 70%) of spleen colony-forming cells at plateau values. The expression of antigens recognized by these and two other anti-stem cell monoclonal antibodies has been shown to correlate with the differentiation status of a panel of tumor cell lines, with greater expression being observed on cells more closely resembling the pluripotent stem cell than mature hemopoietic cells. Immunoperoxidase staining of bone marrow showed that these antigens are mainly expressed by monocytes and blast cells. Treatment of bone marrow cells with those antibodies which extensively inhibited spleen colony formation and with rabbit complement abolished the ability of progenitor cells to form colonies in soft agar. Quantitative absorption studies distinguished the antigens recognized by two of the anti-stem cell monoclonal antibodies from those detected by anti-H-2k 11-4.1 monoclonal antibody. These observations suggest that the antigens involved may play a role in the regulation of growth and differentiation of stem cells and undifferentiated leukemic cells.

Animals↗

PubMed1982

Monoclonal antibodies detect subpopulations of bone marrow stem cells.

Hybridomas secreting monoclonal antibodies cross-reacting with the mouse bone marrow stem cell (CFUs) have been derived from rats immunized with mouse thymocytes and platelets, cells which have been shown to exhibit antigenic lineage relationships with the stem cell. Anti-stem cell activity in hybridoma supernatants occurs at low frequency. Of 418 hybridomas screened, 6 showed initial positivity while two yielded stable cloned cell lines. Both of these monoclonal antibodies, 1C10 and 13C6, bind to subpopulations of stem cells in the bone marrow resulting in 50-65% inhibition of spleen colony formation in lethally irradiated mice. Protein-A binding studies showed the antibodies to be rat IgG. Quantitative absorption and indirect binding studies suggest that the antigens recognized by 1C10 and 13C6 monoclonal antibodies are minor components of the inoculating cell membrane. 1C10 and 13C6 bind to minor subpopulations of cells in the bone marrow, 13 and 5% of cells being rosetted, respectively, at plateau values. These results indicate that, used in conjunction with other monoclonal antibodies or selection tecniques, these antibodies may be useful in stem cell purification.

Animals↗

PubMed1981

Effects of chronic modification of dietary fat and carbohydrate in rats.

1. Rats were fed on diets enriched with starch, sucrose, corn oil or beef tallow for 3 weeks and the activities of various enzymes in the liver were measured. 2. The mitochondrial glycerol phosphate acyltransferase activity was lower in rats fed on the starch diet than on the two high-fat diets. 3. The non-microsomal (presumably peroxisomal) dihydroxyacetone phosphate acyltransferase activity was higher in rats fed on the starch diet and corn-oil diets than in those fed on the sucrose and beef-tallow diets. Urate oxidase activity was higher in rats fed on the starch diet than in the three other groups. There were no significant differences in the activity of acyl-CoA oxidase among the groups. 4. The activity of soluble phosphatidate phosphohydrolase was not significantly different among the dietary groups. There were increases of 3.3--4.3-fold in this activity in the dietary groups 6h after injection of corticotropin. The equivalent increases for the mitochondrial glycerol phosphate acyltransferase were 1.4--1.6 fold. 5. The corticosterone responses to the corticotropin injection were not significantly different between dietary groups. However, the corticosterone response of the rats fed on the two high-fat diets was prolonged when the rats were given an acute load of fructose [Brindley, Cooling, Glenny, Burditt & McKechnie (1981) Biochem. J. 200. 275--283]. 6. Rats fed on the high-fat diets had higher concentrations of circulating cholesterol than those fed on the starch and sucrose diets. Serum triacylglycerol concentrations were lower in the rats fed on the starch diet than in the three other groups. 7. The results are discussed in terms of the relationship between diet, hormonal balance and hepatic glycerolipid metabolism.

Adrenocorticotropic Hormone↗

PubMed1980

Subunit structure of the reovirus spike.

Cross-linking reovirus spike protein with the bifunctional reagent dimethyl suberimidate revealed that each spike was composed of a pentameric aggregate of polypeptide lambda 2.

Cross-Linking Reagents↗