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Biomedical subjects

R Priest

Publications and source records attributed to R Priest.

25 records · Page 2Linked to original sources
PubMed1989

Tumor necrosis factor mediates autocrine growth inhibition in a chronic leukemia.

Autocrine production of growth factors may contribute to the rapid and fatal proliferation of acute hematologic malignancies. We have investigated whether the more controlled growth of less aggressive malignancies such as chronic myeloid leukemia (CML) may be associated with autocrine production of growth inhibitory factors. TNF inhibits the growth of both normal and leukemic hemopoietic progenitor cells. We find that exogenous TNF reduces the viability and DNA synthesis of purified myeloid cells from patients with CML and inhibits myeloid colony formation by patient progenitor cells. However, unlike progenitor cells from normal donors, patient myeloid progenitor cells also constitutively express mRNA for TNF and secrete functional TNF protein in culture. This endogenous TNF impedes the growth of CML cells because anti-TNF mAb shown to neutralize bioactive human TNF increases CML cell DNA synthesis whereas non-neutralizing anti-TNF mAb has no effect. Production of TNF by CML cells is not associated with production of lymphotoxin (TNF-beta), IL-1 or IL-6. TNF-mediated autocrine growth inhibition may contribute to the maintenance of the stable, chronic phase of this disease and similar mechanisms may operate in other malignancies to limit tumor proliferation. Competition between autocrine growth promoting and inhibiting factors may underlie the observed differences in biologic behavior between acute and chronic malignancies.

Antibodies, Monoclonal↗
PubMed1989

Demonstration of cytokines in biological medicines produced in mammalian cell lines.

Commercially produced biological medicines may contain cytokines secreted by mammalian cell lines. Several such cell lines were found to produce interleukin 6 and, after stimulation, to secrete interleukin 1, tumour necrosis factor, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor. High levels of interleukin 6 were detected in several vaccines and rDNA-derived proteins, and certain vaccines contained interleukin 1, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor. Some preparations of human monoclonal antibodies were also found to contain interleukin 1 and tumour necrosis factor. Cytokines may contribute to certain types of adverse reactions to these products.

Animals↗
PubMedDate not supplied

Modulation of sialyl Lewis X dependent binding to E-selectin by glycoforms of alpha-1-acid glycoprotein expressed in rheumatoid arthritis.

Alpha-1-acid glycoprotein (AGP) is an extensively glycosylated acute phase protein of imprecisely defined physiological function. Nonetheless it is known that the oligosaccharide component comprising 42% of the 41 kDa molecular weight is critical to the previously described multifarious immunomodulatory functions of AGP in vitro. Complex oligosaccharides were enzymically released from AGP purified from the blood of rheumatoid arthritis sufferers by our oligosaccharide protective method. Oligosaccharide profiling was by means of high pH anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD). Monosaccharide composition analysis revealed increased fucosylation of inflammatory AGP oligosaccharide chains, suggesting the potential for expression of the tetrasaccharide antigen and E-Selectin ligand, sialyl Lewis X (sLeX). The hypothesis that AGP may function to inhibit blood cell binding to activated endothelium at E-Selectin was tested in a microtitre cell-protein binding assay. In this system we have shown that the oligosaccharide moiety of AGP, as expressed in inflammatory disease, can inhibit the sLeX/E-Selectin interaction. Thus we have identified a correlation between the abnormal glycosylation of AGP in rheumatoid arthritis and suppression of sLeX dependent cell adhesion through inhibition of E-selectin binding which could be the basis of a novel, site specific, anti-inflammatory agent.

Animals↗