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Biomedical subjects

M J Egorin

Publications and source records attributed to M J Egorin.

9 recordsLinked to original sources
PubMed1979

Phaseolus vulgaris isolectin binding to human erythrocytes.

The Phaseolus vulgaris isolectins L4,L3E1, L2E2, L1E3, and E4 were isolated by affinity and ion exchange chromatography. Pure isolectins were radiolabeled by the chloramine-T method with Na125IO4 and their binding to human erythrocytes was studied. A normal erythrocyte has approximately 8 times 10(5) receptor sites for each isolectin; however, the association constants (Ka) of binding increased from 1.1 times 10(7) M-1 to 3.8 times 10(8) M-1, with increasing number of E subunits per tetrameric isolectin molecule. Isolectin to erythrocyte binding reached equilibrium rapidly and was reversed by fetuin. All isolectins competed with 125I-E4 for erythrocyte binding sites, with a constant (KI) similar to the Ka calculated for each respective radiolabeled isolectin. When isolectin binding at 0 degrees C, 4 degrees C, or 8 degrees C was compared to that at 25 degrees C, there was no reduction in the number of binding sites per cell, but the Ka of E4 was reduced to 3 times 10(7) M-1. Fixed erythrocytes displayed similar isolectin binding characteristics.

Binding Sites↗
PubMed1979

Cellular pharmacology of 7(R)-O-methylnogarol: a new anticancer agent.

The cellular accumulation and disposition of 7(R)-O-methylnogarol (7-OMEN), a derivative of the anthracycline antibiotic, nogalamycin, were compared to those of daunorubicin. Although both drugs were avidly accumulated by cells, intracellular concentrations of 7-OMEN were 5 to 10 times those of daunorubicin. Lowered temperature (0 degrees C) reduced intracellular accumulation of both drugs, but 10 mM sodium azide reduced the accumulation of 7-OMEN only. Both drugs exited from cells placed in drug-free medium, a process that was reduced at 0 degrees C. Sodium azide, 10 mM, did not alter the efflux of daunorubicin from cells but hastened the efflux of 7-OMEN. Unlike whole cells, isolated nuclei accumulated more daunorubicin than 7-OMEN. This process was not reduced at 0 degrees C. Both drugs were lost from nuclei placed in drug free buffer with only slight reduction at 0 degrees C. Unlike daunorubicin which localized in cell nuclei, 7-OMEN localized in the cytoplasm with no detectable nuclear fluorescence. Both drugs produced nearly equivalent dose-dependent inhibition of [3H]thymidine incorporation by L1210 and P388 cells. P388/ADR cells proved resistant to both anthracyclines. [3H]uridine and [3H]valine incorporations were inhibited by daunorubicin but were not altered by 7-OMEN.

Animals↗
PubMed1979

Cellular accumulation and disposition of aclacinomycin A.

The cellular accumulation and disposition of the anthracycline antitumor antibiotic aclacinomycin A (ACM) were compared to those of daunorubicin. Although both drugs were avidly accumulated by cells, intracellular concentrations of ACM were two to three times those of daunorubicin. Whereas lowered temperature (0 degrees) reduced intracellular accumulation of both drugs, 10 mM sodium azide had no effect on accumulation of either ACM or daunorubicin. Both drugs exited from cells placed in drug-free medium, a process that was reduced at 0 degrees but not altered by 10 mM sodium azide. Unlike whole cells, isolated nuclei accumulated more daunorubicin than ACM. This process was not altered at 0 degrees. Both drugs were lost from nuclei placed in drug-free buffer, a process that was reduced at 0 degrees. Unlike daunorubicin, which localized in cell nuclei, ACM localized in the cytoplasm with no detectable nuclear fluorescence. Although both drugs produced dose-dependent inhibitions of [3H]thymidine and [3H]uridine incorporation by L1210 and P388 cells, ACM inhibited both processes at lower concentrations than did daunorubicin. While daunorubicin inhibited [3H]thymidine incorporation more effectively than [3H]uridine incorporation, the reverse was observed with ACM.

Animals↗
PubMed1978

Inhibitory effects of phytohemagglutinin isolectins L4 and E4 on L1210 cells.

Phytohemagglutinin isolectins L4 and E4 inhibit the growth and proliferation of cultured L1210 murine leukemia cells. L1210 cells were incubated with L4 or E4, and the metabolic and morphological characteristics of the cells were assessed. Dose-dependent inhibition of up to 90% occurs for [3H]thymidine and [14C]uridine incorporation. L4 is 30 to 50 times more potent an inhibitor than is E4. Inhibition begins 2 to 3 hr after exposure of L1210 cells to L4 and persists for as long as the cells are exposed to this isoleuctin. Total DNA and oxygen consumption in L4-treated cultures is also decreased. Whereas protein synthesis assessed by [14C]valine incorporation is less affected, glucose utilization remains unchanged. The binding of L4 and E4 to L1210 cells and human lymphocytes is similar and is reversible by porcine thyroglobulin. Porcine thyroglobulin also reverses L4-induced inhibition of nucleotide incorporation. Cell aggregation is the major morphological consequence of isoleuctin treatment observed by light or electron microscopy. L1210 cells are agglutinated at lower doses of isoleuctins than are normal murine lymphocytes. No evidence of cell death as estimated by 51Cr release or trypan blue uptake has been noted. Our data indicate that L4 and E4 have cytostatic properties and demonstrate that the reversible binding of a macromolecule to the surface of a malignant cell can modulate synthetic pathways and the rate of proliferation.

Animals↗
PubMed1977

Recombinations of subunits of Phaseolus vulgaris isolectins.

Phaseolus vulgaris phytohemagglutinin is formed in vivo by the combination of erythrocyte (E)-reactive and lymphocyte (L)-reactive subunits into five tetrameric isolectins:L4,L3E1, L2E2, L1E3, and E4. Evidence for phytohemagglutinin subunit structure is obtained by in vitro dissociation of native isolectins in 6 M guanidine HCl followed by removal of dissociating agents to allow subunit recombination. Dissociation and recombination of L4 yielded a single protein, electrophoretically indistinguishable from the native L4. Similar treatment of E4 also yielded a single protein indistinguishable from native E4. Treatment of L3E1, L2E2, L1E3, or a mixture of L4 and E4, yielded five distinct proteins electrophoretically similar to all five native phytohemagglutinin isolectins. Milligram quantities of all five recombinant isolectins were prepared either from L2E2 or a mixture of L4 and L1E3 proportioned to yield equimolar quantitives of the two subunits on dissociation. The recombinant isolectins were purified by affinity and SP-Sephadex ion exchange chromatography. Electrophoretic and chromatographic properties and the erythroagglutinating and mitogenic activities of recombinant isolectins were essentially identical with the native isolectins. The inclusion of 125I-labeled L4 in the dissociation results in a distribution of 125I-labeled L subunit among the purified recombinant isolectins proportional to their proposed subunit structures.

Chemical Phenomena↗