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Biomedical subjects

T S Edgington

Publications and source records attributed to T S Edgington.

At least 163 records · Page 9Linked to original sources
PubMed1981

Plasma lipoproteins with bioregulatory properties including the capacity to regulate lymphocyte function and the immune response.

Consideration of the effects of nutrition and of lipids on the immune competence and the characteristics of host resistance to neoplasia requires consideration of the plasma lipoproteins. A wide variety of regulatory effects of lipoproteins on the immune response, immune mediation pathways, cellular metabolism of the immune system, and antigen-nonspecific host resistance mediated by the lymphoid and reticuloendothelial systems has recently been recognized. Observations coupled with initial evidence for differences in lipoproteins in cancer patients suggest that lipids or lipid metabolism may be of significance in the biology of neoplasia.

Animals↗
PubMed1981

Immunoregulatory plasma low density lipoprotein: the biologic activity and receptor-binding specificity is independent of neutral lipids.

A normal human plasma low density lipoprotein subfraction (LDL-In), recovered within the intermediate density lipoprotein subclass of density range 1.006 to 1.019 g/ml, has previously been demonstrated to bind to a specific cell surface receptor independent of the LDL receptor and to regulate inductive events in the triggering of lymphocytes. The constituents of LDL-In that are responsible for the biologic activity and receptor-binding specificity were examined with respect to the role of sterols and other neutral lipids. Partial delipidization of LDL-In with heptane in the presence of starch permitted selective extraction of greater than 98% of the neutral lipids from the native lipoprotein particle. These partially delipidated polar lipid:protein particles were compared with native LDL-In with respect to charge, apoprotein content, suppressive activity for lymphocytes, and specific binding to the lymphocyte LDL-In receptor. The cholesterol- and glyceride-depleted LDL-In retained all characteristics of the native lipoprotein. These observations indicate that the interaction of LDL-In particles with the lymphocyte and the suppression of lymphocyte function are independent of the neutral lipid content of this bioregulatory lipoprotein, and that mechanisms other than cholesterol loading of the cell or sterol exchange with the plasma membrane must be operative.

Binding Sites↗
PubMed1980

Lymphocyte cooperation is required for amplification of macrophage procoagulant activity.

Murine splenic lymphoid cells have been shown to possess basal procoagulant activity. This activity was localized to most macrophages by assay of cell populations, as well as by a direct plaque assay that permitted identification of expressed procoagulant activity of individual viable cells as well as content. Both content and viable expression of procoagulant activity was markedly increased by exposure to bacterial lipopolysaccharide, reaching a maximum after 6 h. The quantitative increase in procoagulant activity content and viable expression was limited to the macrophage population. Separated populations of lymphocytes or macrophages could not be stimulated by lipopolysaccharide to increase procoagulant activity, whereas the addition of lymphocytes to macrophages at a 3-4:1 ratio maximally reconstituted the amplification of procoagulant activity. Further evidence of cellular collaboration followed from observation that only lymphocytes that had been exposed to lipopolysaccharide were capable of triggering the increase in macrophage procoagulant activity. This appears to represent a new form of lymphocyte-macrophage cooperation in an effector pathway that may participate in some forms of immunologic responses and contribute to the phenotypic features of certain immunologic tissue lesions.

Animals↗
PubMed1980

Activation of rabbit Hageman factor by homogenates of cultured rabbit endothelial cells.

Rabbit Hageman factor was proteolytically cleaved and activated by a homogenate prepared from cultured rabbit endothelial cells. Cleavage of radiolabeled Hageman factor was monitored by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Endothelial cell-mediated cleavage of Hageman factor was demonstrated both in a purified system and in plasma, was time and concentration dependent, and was associated with formation of the characteristic 28,000 M(r) form of active Hageman factor. The rate of cleavage of Hageman factor was not affected by Triton X-100 (Rohm and Haas, Co., Philadelphia, Pa.), hexadimethrine bromide (Polybrene, Aldrich Chemical Co., Inc., Milwaukee, Wis.), hirudin, soybean trypsin inhibitor, or antisera to plasminogen or prekallikrein. However, cleavage was enhanced by kaolin, and was inhibited by diisopropyl-fluorophosphate. The enzyme responsible for cleavage of Hageman factor was localized to the 100,000-g-sedimentable, subcellular fraction of the endothelial cell homogenate and was relatively specific, because neither radiolabeled rabbit Factor XI nor rabbit prekallikrein were themselves proteolytically cleaved by the endothelial cell homogenate. However, when these molecules were incubated with the homogenate in the presence of Hageman factor, both Factor XI and prekallikrein were cleaved, demonstrating that Hageman factor had been activated by the endothelial cell homogenate. Furthermore, the kallikrein generated by endothelial cell homogenate-activated Hageman factor was capable of liberating kinin from high molecular weight kininogen as measured by bioassay. Cultured rabbit endothelial cells, therefore, possess the capacity to activate Hageman factor by proteolysis. This may be one mechanism for Hageman factor activation in vivo.

Animals↗
PubMed1980

Direct suppression of lymphocyte induction by the immunoregulatory human serum low density lipoprotein, LDL-In.

Preparations of LDL-In, an immunosuppressive lipoprotein subfraction, were analyzed for the capacity to directly suppress the response of human lymphocytes to the representative stimulant PHA vis-a-vis indirect mechanisms mediated by soluble factors or cell:cell interactions. Serum lipoprotein subfraction enriched in LDL-In induced a suppressed state in lymphocytes during 18-hr induction cultures. These lymphocytes, whether partially or completely suppressed, when added to fresh responder lymphocytes in the presence of PHA did not suppress the response of the responder lymphocytes. In contrast, the major low density lipoprotein (LDL) did not suppress lymphocytes at equivalent concentration in the induction culture, nor did LDL-exposed lymphocytes suppress responder lymphocytes. The supernatant medium from LDL-In-suppressed lymphocytes did not contain a newly synthesized or released suppressive factor. Finally, LDL-In-suppressed lymphocytes were not rescued by normal lymphocytes. Each of these observations, and previous evidence that adherent cells do not mediate the biologic effects of LDL-In, support the hypothesis that the biologic manifestations of LDL-In suppression of lymphocyte function result from a direct effect on the lymphocyte that is exposed to this lipoprotein, possibly via the previously demonstrated LDL-In receptor.

Cell Communication↗
PubMed1980

Radioimmunoassay for tissue distribution of a human mammary tumor-specific glycoprotein.

The candidate tumor-specific soluble mammary tumor glycoprotein with a molecular weight of approximately 20,000 (MTGP20) has been isolated from human breast carcinomas and characterized biochemically. Although with the use of xenoantisera this glycoprotein has previously been demonstrated only in breast carcinomas, analyses of body fluids and conclusions regarding putative tumor specificity have been limited by the sensitivity of assays. In the present study, a specific radioimmunoassay has been developed. With appropriate selection of buffer, the assay has a sensitivity threshold of less than 0.1 unit of MTGP20 per ml, equivalent to less than 250 pg type I MTGP20 per ml or less than 530 pg type II MTGP20 per ml, which is more than 200-fold more sensitive than previously described assays. MTGP20 type I, which contains tyrosine, was labeled with 125I and used as the immunochemical ligand in a double antibody competitive inhibition assay. A partial weak cross-reaction was observed with a mixture of placental glycoprotein (perchloric acid extract), but this reaction was abolished by absorption of antisera with placental glycoprotein. Normal tissue and tumors of other than breast origin were devoid of MTGP20-related antigens. MTGP20-related antigens were not detectable in sera or concentrated urine specimens from normal individuals or patients with metastatic breast carcinomas. The present studies further support the probable tumor specificity of this glycoprotein but indicate that it does not represent a circulating secretory product of the cancer cell and does not provide a serum marker for breast carcinoma.

Animals↗
PubMed1980

Subcellular localization of the sedimentable form of mammary tumor glycoprotein to the tumor cell plasmalemma.

A form of mammary tumor glycoprotein (MTGP) has been observed to be associated with the sedimentable fraction of homogenates of human carcinomas of the breast. A MTGP-containing breast carcinoma cell line, HS-578T (AY-726), containing both soluble and sedimentable forms of MTGP, was fractionated by differential ultracentrifugation, discontinuous sucrose gradient and on a polyethylene glycol-dextran gradient. The separated crude nuclei fraction, crude mitochondrial fraction, disrupted organelles, ribosomes and rough microsomes, smooth microsomes, and plasmalemma were characterized by electron microscopy and enzymatic markers which confirmed that each fraction was highly enriched in the respective subcellular constituents. Analysis of insoluble MTGP demonstrated significant coisolation with the plasmalemma. On the basis of the present data showing that the sedimentable form of MTGP is firmly associated with the plasmalemma and previous evidence showing the specificity of MTGP for breast carcinoma cells and the surface exposure of MTGP on viable cells, we conclude that sedimentable MTGP is an integral membrane glycoprotein that could have biological significance in the behavior or immunobiology of these tumors.

Breast Neoplasms↗
PubMed1980

Lymphoid procoagulant activity and mitogenesis in the C3H/HeJ mouse: discordant response to lipopolysaccharide stimulation.

Lymphoid cells from the C3H/HeJ mouse respond abnormally to bacterial lipopolysaccharide (LPS) in a number of in vitro functions. Abnormalities in both macrophage and lymphocyte populations have been suggested. In the present study, splenic mononuclear cells were isolated from C3H/HeJ, C3H/St, A/J, and BALB/c mice, and analyzed for mitogenesis and induction of procoagulant activity (PCA) by LPS prepared by either phenol or butanol extraction methods. All strains responded vigorously with resultant increased 3H thymidine uptake to Con A and PHA, and all but the C3H/HeJ responded well to butanol or phenol extracted LPS. However, the C3H/HeJ was unresponsive to phenol-extracted LPS and exhibited a poor but significant response to butanol-extracted LPS. In contrast, lymphoid cells from all strains, including the C3H/HeJ, exhibited a marked and equal increase of PCA in response to both phenol- and butanol-extracted LPS by using both splenic and peripheral blood lymphoid cells. The results obtained indicate that although the C3H/HeJ mouse may be unresponsive to a number of LPS-stimulated functions, there is no associated defect in PCA generation, a lymphocyte collaboration-dependent event.

Animals↗
PubMed1980

Differences in the characteristics of inhibition of lymphocyte stimulation by 25-hydroxycholesterol and by the immunoregulatory serum lipoprotein LDL-In.

Suppression of peripheral blood lymphocyte phytohemagglutinin-stimulated 3H-thymidine uptake in vitro by serum lipoprotein fractions enriched in the immunoregulatory low density lipoprotein (LDL-In) and by 25-hydroxycholesterol was compared to determine whether the biologically active constituent of LDL-In might be an oxygenated sterol. Dose titrations indicated that 25-hydroxycholesterol was 100 times more potent than LDL-In on the basis of total sterol. Both were similar in that maximal inhibitory activity was evident when they were present in the cultures for at least 24 hr before mitogen stimulation. However, the suppression of 3H-thymidine uptake by 25-hydroxycholesterol required the continuous presence of the sterol, whereas equivalent suppression by LDL-In was irreversible and did not require the presence of the lipoprotein beyond the preincubation period. 25-Hydroxycholesterol-mediated suppression of 3H-thymidine uptake was mitigated by the addition of cholesterol or mevalonic acid to the lymphocyte cultures, consistent with an effect on sterol biosynthesis, whereas, LDL-In mediated suppression was not. Finally, when chloroquine was used to inhibit lymphocyte lysosomal hydrolysis, which is required for the intracellular degradation and release of cholesterol esters from internalized low density lipoprotein, the phenotypic expression of LDL-In mediated suppression was not altered, indicating that this known pathway of regulation of cellular function by low density lipoproteins is not the primary mode of action of LDL-In. These data indicated that the mode of suppression of mitogen-stimulated thymidine uptake by serum lipoprotein fractions enriched in LDL-In differs from that produced by 25-hydroxycholesterol, and that LDL-In suppression does not appear to result from inhibition of intracellular cholesterol biosynthesis.

Cell Division↗
PubMed1979

Internalization of the amino terminal 1-78 sequence of the gamma chain of native fibrinogen and exposure associated with catabolism and plasmin cleavage.

Specific antibodies of the gamma 1--78 peptide of human fibrinogen were employed in binding assays and in equilibrium competitive inhibition assays to analyze the expression of gamma 1--78 antigenic determinants as an indication of the relative exposure of the gamma 1--78 sequence in the E domain of fibrinogen, high solubility fibrinogen subfractions I-8 and I-9, and plasmic cleavage fragments of fibrinogen and fibrin. A very limited exposure of gamma 1--78 sequences was found to occur concomitant with proteolytic deletions of the major carboxyterminal segment of the A alpha chains in fgI-8, fgI-9. Exposure of gamma 1--78 is not influenced by further proteolysis to fg-X which is associated with B beta 1--43 deletion. Further proteolysis to fg-Y, which is associated with deletion of beta 43--53 and of one of the D domains, is associated with additional exposure of gamma 1--78. This is not significantly influenced by further proteolysis to fg-E with deletion of the second D domain, deletion of A alpha 1--19, and proteolysis at the carboxyterminal aspects of the E domain chains.

Amino Acid Sequence↗