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Biomedical subjects

J R David

Publications and source records attributed to J R David.

At least 235 records · Page 13Linked to original sources
PubMed1975

Multiple in vitro mechanisms of tumor cytotoxicity demonstrated in the line-1 guinea pig hepatoma model.

The line-1 guinea pig hepatoma was used to study in vitro tumor cytotoxicity. Cytotoxicity was determined by measurement of the loss of tritiated thymidine-labeled target cells from culture vessels. With this technique, we demonstrated that significant tumor cytotoxicity was caused by lymphoid cells from tumor-immune guinea pigs, by cells from guinea pigs immunized against an antigen urelated to the tumor target, and by cell-free supernatants rich in lymphocyte mediators. Addition of normal peritoneal exudate cells enhanced the cytotoxic potential of a small number of highly purified immune lymphocytes, which suggested that recruitment of normal cells is an additional mechanism of tumor cell death in this system.

Animals↗
PubMed1975

Macrophage activation induced by lymphocyte mediators.

This paper is a brief review of studies which demonstrate that lymphocyte mediators can activate macrophages in vitro. Macrophages which have been incubated in lymphocyte mediator-rich Sephadex fractions show changed morphology, metabolism and function. These changes include an increase in adherence to glass. ruffled membrane movement, phagocytosis of some particles, glucose oxidation through the hexose monophosphate shunt and an increase in the activity of a membrane enzyme, adenylate cyclase. Such mediator-activated macrophages show enhanced bacteriostasis and tumoricidal activity. In addition, studies describing the role of membrane sugars and esterases in the interaction of migration inhibition factor and macrophages are reviewed.

Adenylyl Cyclases↗
PubMed1975

Studies on the production of MIF and mitogenic factor using highly purified human T and B lymphocytes.

Human lymphocytes were separated into highly purified populations using an immunoadsorbent column technique. It was previously reported that both T and B cells exhibited increased 3H-thymidine incorporation in response to PHA, Con A and pokeweed mitogens, whereas only T cells showed increased incorporation in response to specific antigen. In the present studies, the cellular basis of MIF and mitogenic factor production was studied. Both T and B cells produced MIF in response to antigen. The MIF produced by both T and B cells elutes from Sephadex G-100 columns in the same fraction. Studies using BUdR and light suggest that the T cell which produces MIF is also a proliferating cell, whereas the B cell producing MIF is not. Only T cells produce mitogenic factor in response to antigen. The mitogenic factor produced, however, causes both T and B cell populations to increase 3H-thymidine incorporation. The present studies indicate that antigen induced mitogenic factor production and increased 3H-thymidine incorporation are properties of T cells per se, whereas antigen-induced MIF is made by both T and B cells.

Antigens, Bacterial↗
PubMed1975

Macrophages activated as suspension cultures with lymphocyte mediators devoid of antigen become cytotoxic for tumor cells.

Normal peritoneal exudate cells (PEC) were activated as suspension cultures either in mediator-rich supernatants from o-chlorobenzoyl-bovine gamma-globulin (OCB-BGG) stimulated lymphocytes or in antigen-free Sephadex fractions from these supernants. After 24 hr incubation thration. The adherent cell fractions of PEC, recovered by trypsinization from monolayers and activated by this technique, were as cytotoxic as unfractionated PEC. Lymphocyte supernatants and antigen-free fractions of the supernatants induced comparable macrophage-mediated tumor cytotoxicity. Treatment of activated macrophages with trypsin did not alter their cytotoxic capacity.

Animals↗
PubMed1975

Studies on the mechanism of suppression of delayed hypersensitivity by the antischistosomal compund niridazole.

Niridazole given in a single oral dose of 100 mg/kg to guinea pigs sensitized to ortho-chlorobenzoyl chloride-bovine gamma-globulin (OCB-BGG) regularly abolished delayed cutaneous reactivity. Little effect was observed, however, when cells from these animals were tested in vitro with either direct or indirect assays for migration inhibitory factor (MIF). On the other hand, sera taken from nonsensitized guinea pigs after they had received 100 mg/kg of niridazole markedly diminished antigen-induced inhibition of migration of sensitized peritoneal exudate cells in vitro. The immunosuppressive effects of such sera could not be produced by niridazole itself, thereby suggesting an effect of niridazole metabolites. This suppressive activity was readily removed from the serum by dialysis. The active serum blocked the production of MIF by sensitized lymph node cells but did not affect the action of preformed MIF on macrophages. The effect of this serum was reversible; lymph node cells incubated for 24 hr with active serum, then washed and reincubated with antigen in normal serum, produced normal amounts of MIF. These studies suggest that metabolites of niridazole, but not the parent compound itslef, suppress delayed hypersensitivity in guinea pigs and prevent MIF production by lymphocytes without affecting the macrophage response to MIF.

Animals↗
PubMed1974

Studies on mediator production by highly purified human T and B lymphocytes.

Highly purified populations of T and B lymphocytes obtained by affinity column separation were stimulated by antigen and their ability to produce two mediators, migration inhibitory factor (MIF) and lymphocyte mitogenic factor (LMF) was assessed. Both T- and B-cell populations made MIF; the production of MIF was antigen-specific using purified protein derivative of tuberculin, streptokinase-streptodornase, and Candida antigens. The MIF activity from both populations could not be attributed to antigen-antibody complexes as the inhibitory activity eluted from Sephadex G-100 columns in the same region corresponding to mol wt 23,000 daltons. Further studies indicate that the T cells producing MIF are proliferating cells whereas the B cells producing this mediator are not. In contrast, LMF was made only by T cells and not B cells when these populations were stimulated by antigen. The LMF induced the [(3)H]thymidine incorporation into both T and B cells obtained from donors lacking sensitivity to the antigens used to elicit the factor. Chromatographic studies indicate that LMF eluted from Sephadex G-100 in a fraction of mol wt 23,000 daltons where MIF is also found; however, since B cells produce MIF but not LMF, these two factors appear to be distinct from one another. Some of the implications of these findings are discussed. The explanation for the production or lack of production of MIF by lymphocytes obtained from patients with immunodeficiency disorders requires reinterpretation.

Antigen-Antibody Reactions↗
PubMed1974

Activation of human blood monocytes by products of sensitized lymphocytes.

Studies were carried out to determine whether products of activated human lymphocytes altered human monocyte function. Supernatants from sensitized human lymphocytes stimulated by specific antigen were cultured with monolayers of human monocytes. Such monocytes exhibited enhanced adherence to their culture vessels and increased glucose carbon-1 oxidation after 2-3 days of incubation. The substance responsible for these effects was found to elute from Sephadex G-100 gel columns in a fraction with 23,000 mol wt, the same fraction containing human migration inhibitory factor.

Cell Adhesion↗
PubMed1973

The enhancement of macrophage bacteriostasis by products of activated lymphocytes.

It was reported previously that the incubation of normal guinea pig macrophages with partially purified products of activated lymphocytes resulted in altered macrophage function including increased cell adherence to culture vessels, spreading, phagocytosis, and glucose carbon-1 oxidation. Studies reported here demonstrate that such macrophages also exhibit enhanced bacteriostasis. Lymphocytes were stimulated with concanavalin A, the culture supernatant was chromatographed over Sephadex G-100 and the fraction of mol wt 25,000-55,000, rich in lymphocyte mediators, was cultured with normal guinea pig macrophages for 1-3 days. Macrophages incubated with fractions from unstimulated lymphocyte cultures served as controls. The resulting macrophage monolayers were infected with Listeria monocytogenes. Macrophages incubated with mediator-rich fractions exhibited 2- to 10-fold enhanced bacteriostasis compared to controls. Further studies indicate that this enhancement was attributable to intrinsic changes in the macrophages and not simply a consequence of the number of macrophages on the monolayers. The studies support the concept that macrophage bacteriostasis can be enhanced by lymphocyte mediators. However, macrophages, which have been preincubated directly with sensitive lymphocytes and antigen exhibit even greater bacteriostasis and sometimes bactericidal capacity, suggesting that either a labile lymphocyte factor or direct lymphocyte macrophage interaction may also be involved in bactericidal activity.

Animals↗
PubMed1973

Characterization of a lymphocyte factor which alters macrophage functions.

As reported previously, antigenically stimulated guinea pig lymphocytes elaborate a soluble factor which activates macrophages in the sense of promoting increased adherence, spreading, phagocytosis, and glucose oxidation through the hexose monophosphate pathway. Further studies on the characteristics and kinetics of this substance were carried out. The activating factor could not be distinguished from a previously characterized lymphocyte mediator, migration inhibitory factor (MIF), on the basis of Sephadex G-100 gel filtration, CsCl density gradient centrifugation, or sensitivity to neuraminidase. It was, however, shown to be distinct from two other lymphocyte mediators, chemotactic factor for macrophages and lymphotoxin. The kinetics of activation were further studied. The data suggest that the 3 day period required by macrophages to manifest a response to the activating factor consists of two stages. In the first, requiring 1-2 days, the macrophages are refractory to the influence of activating factor, but undergo changes which render them receptive. In the second, they respond to activating factor with increased cell adherence and glucose oxidation. Once macrophages have been activated, the effect persists in the absence of activating factor for 24 h. Finally, it was shown that activation in unfractionated supernatants followed the same time-course as that in more purified fractions. The data suggests that the activating factor is the same as MIF and that, in vitro, macrophages respond to this substance with migration inhibition before they become sensitive to its activating influence.

Animals↗