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Biomedical subjects

T Borsos

Publications and source records attributed to T Borsos.

At least 73 records · Page 4Linked to original sources
PubMed1978

Identification of lipids associated with the ability of tumor cells to resist humoral immune attack.

Certain metabolic inhibitors or chemotherapeutic agents that increase the susceptibility of line-1 or line-10 guinea pig hepatoma cells to humoral immune attack were studied for their effects on the ability of the cells to synthesize lipids. A direct correlation was found between the drug-induced increase in sensitivity to antibody-C mediated killing and the inhibition of the ability of the cells to incorporate acetate, glycerol, and fatty acids into complex cellular lipids. Drug-treated cells recultured in drug-free medium regained their resistance to antibody-C mediated killing; these cells recovered their ability for complex lipid synthesis at this time. Thin layer chromatography of CHCl3:CH3OH lipid extracts from these cells indicated that the drug-induced increase in susceptibility to humoral immune attack correlated with the inhibition of acetate, glycerol, and fatty acid incorporation into cardiolipin and triglyceride in line-10 cells and the inhibition of incorporation of these compounds into cardiolipin alone in line-1 cells. No direct correlation was found between the sensitivity of the cells to humoral immune attack and the ability of the cells to incorporate precursors of lipid synthesis into other lipid moieties (sphyngomyelin, phosphatidyl serine, phosphatidyl choline, phosphatidyl glycerol, or cholesterol esters). The synthesis of cardiolipin and triglycerides, therefore, appears to be associated with the mechanism whereby these tumor cells resist antibody-C mediated killing.

Acetates↗
PubMed1978

Correlation between the ability of tumor cells to incorporate specific fatty acids and their sensitivity to killing by a specific antibody plus guinea pig complement.

Line-1 diethylnitrosamine-induced guinea pig tumor cells can be rendered sensitive to killing by rabbit anti-Forssman IgM antibody plus guinea pig complement (GPC) or antitumor antibody plus GPC following prolonged incubation (17 hr ) of the cells with one of several metabolic inhibitors. Compared to control cells, these cells have been shown to be inhibited in their ability to incorporate fatty acids into complex cellular lipids, which suggested that lipid synthesis is of fundamental importance for the ability of the tumor cells to resist humoral immune killing. In this study, drug-treated cells that were rendered sensitive to killing by anti-Forssman antibody plus GPC, but not antitumor antibody plus GPC, were inhibited in their incorporation of saturated (palmitic or stearic acid), but not an unsaturated, fatty acid (linoleic acid). These data suggested that the fatty acid composition of specific lipids may also be important for the resistance of these tumor cells to killing by antibody and complement.

Animals↗
PubMed1978

Studies on the interaction between protein A and immunoglobulin G. I. Effect of protein A on the functional activity of IgG.

Staphylococcal protein (A (PA) and IgG anti-Forssman immunoglobulin formed complexes that behaved functionally like IgM in their ability to lyse sheep erythrocytes (E) in the presence of whole guinea pig complement (GPC) and to fix purified guinea pig C1. Concanavalin A, a plant lectin that inhibited IgM but not IgG hemolytic activity, inhibited the hemolytic activity of IgG-protein A complexes that behaved like IgM but had no effect on complexes that behaved functionally like IgG. Since Con A is known to bind specifically to glucose and mannose residues, our results suggested that the interaction of protein A with the Fc region of IgG led to exposure of sugar moieties that may participate in complement (C) binding. The production of IgM-like complexes depended on the ratio of protein A to IgG and the empirical formula of these IgM-like complexes was found to be [(IgG)2PA]n. As the ratio of PA to IgG was increased, the resulting complexes tended to behave functionally like IgG but with reduced hemolytic activity and C1 fixing ability. Furthermore, the binding of C1 to EIgG was inhibited by PA and the binding of PA to EIgG was inhibited by C1 indicating that the binding sites for C1 and PA were located near each other or were identical. Our results offer a reasonable explanation for the reported effects of PA or mixtures of PA and IgG in vitro and in vivo.

Animals↗
PubMed1978

Stimulation of the synthesis and release of lipids in tumor cells under attack by antibody and C.

Antibody-sensitized line-1 or line-10 tumor cells treated with GPC (TAC) incorporated fatty acids into complex cellular lipids and released increased amounts of fatty acids within 5 to 10 min after the addition of GPC as compared to control cells. This effect was dependent on the concentration of GPC used; however, under conditions where the cells were not killed, the enhanced synthesis and release of lipids were not dependent on the antibody concentration used to sensitize the cells. Treatment of the cells with antibody alone, GPC alone, or antibody plus heat-inactivated GPC did not result in enhanced synthesis or release of lipids. No enhancement in DNA, RNA, or protein synthesis in TAC was noted. Line-1 cells, which can be killed by GPC when sensitized with excess anti-Forssman IgM antibody, demonstrated enhanced lipid synthesis within 1 to 3 min after the addition of GPC to the antibody-sensitized cells, before measurable killing of the cells had occurred. This effect persisted in the surviving cells when tested 5 and 10 min after the formation of TAC. Addition of GPC deficient in C4 to antibody-sensitized cells did not result in enhanced lipid synthesis or release. These data suggest that the synthesis of macromolecules of which lipids are a major component is of central importance for the ability of the cells to resist antibody-GPC mediated attack.

Animals↗
PubMed1978

Studies on the terminal stages of immune hemolysis. III. Distinction between the insertion of C9 and the formation of a transmembrane channel.

The intermediate product EAC1-8 released cytoplasmic components as a result of at least two sequential reactions after its interaction with C9. Binding of C9 to EAC1-8 occurred in a few minutes even at 0 degrees C. Trypsinization of EAC1-9 prepared and held at low temperature resulted in nullification of the potential hemolysis of these cells. A brief incubation at 30 or 37 degrees resulted in the formation of an intermediate whose hemolytic potential could not be nullified by trypsin. The failure of trypsin to nullify hemolysis was attributed to the insertion of C9 into the cell membrane. Studies on the effec of EDTA or low temperature suggested that the reported temperature-dependent step in E* formation described by Frank et al. was the insertion of C9. The results of the studies with 86Rb-labeled EAC1-8 indicated that a transmembrane channel was not formed until after the C9 had been inserted and a further reaction or reactions had occurred.

Animals↗
PubMed1977

125I protein A: applications to the quantitative determination of fluid phase and cell-bound IgG.

An improved method for the preparation of 125I-labelled Protein A (125I PA) of high specific and functional activity is described. 125I PA has been used in combination with purified rabbit IgG bound to a solid support to develop a competitive binding assay capable of detecting Protein A or human, rabbit and guinea pig IgG at the nanogram level. An optimal set of assay conditions was established and levels of IgG measured in normal human, rabbit and strain-2 guinea pig serum. 125I PA has also been used to detect IgG anti-Forssman antibody bound to sheep erythrocytes and to line-1 and line-10 tumor cells and as an indirect assay for tumor associated antigen in the ascitic fluid of tumor-bearing guinea pigs.

Animals↗
PubMed1977

Effect of concanavalin A on the functional activity of hemolytic antibody.

Concanavalin A (Con A), either in solution or insolubilized by covalent binding to Sepharose 4B, can inhibit the ability of fluid phase 19S, but not 7S, anti-Forssman antibody to sensitize sheep red cells (E) toward lysis by excess guinea pig complement. The efficiency of 19S antibody is unaffected when E are treated with Con A before sensitization or when antibody sensitized cells (EA) are exposed to the lectin before complement is added. Although whole complement activity is retained on a solumn of Con A-Sepharose, cell bound lectin did not act as a complement fixing antibody. Consistent with this result, there was no difference in the amount of C1 fixed by E and E-Con A, or by EA and EA-Con A.

Animals↗
PubMed1977

Kinetics of hormone-induced tumor cell resistance to killing by antibody and complement.

Line 1, a chemically induced guinea pig hepatoma, is susceptible to killing by anti-Forssman immunoglobulin M antibody and guinea pig complement. When these tumor cells are pretreated with insulin, L-epinephrine, hydrocortisone, or prednisolone, the cells show a marked reduction in their susceptibility to antibody-complement-mediated killing within 15 to 60 min; this effect reverses within 4 hr in the continued presence of hormone. Maximal binding of the hormones to the line 1 cells was observed within 60 min. However, the hormones remained bound to the cells after 4 hr of incubation, suggesting that line 1 cells incubated in the continued presence of hormone revert to the susceptible state despite the persistence of cell-bound hormone. Hormone-treated tumor cells, washed free of hormone and reincubated in hormone-free medium, lost nearly all their bound hormone within 15 to 30 min of washing. These cells, however, remained resistant to antibody-complement-mediated killing for up to 2 hr after washing. Line 1 cells, reverted in the continued presence of hormone, remained susceptible to killing by antibody and guinea pig complement after reexposure to the same, but not to a different, hormone. Hormone-treated cells reverted after prolonged incubation in hormone-free media; however, they were rendered resistant to killing after reexposure to the same hormone. The temporary refractoriness of reverted cells to further hormone stimulation was not due to an inability of the cells to bind hormone.

Animals↗
PubMed1977

Effect of inhibiting DNA, RNA, and protein synthesis of tumor cells on their susceptibility to killing by antibody and complement.

A number of metabolic inhibitors and chemotherapeutic agents have been found to increase the sensitivity of a chemically induced guinea pig hepatoma (line 1) to killing by antibody and complement. We have investigated whether the mechanism whereby these drugs increase sensitivity to killing is attributable to their primary action of inhibiting DNA, RNA, or protein synthesis. Line 1 cells incubated for 1, 4, or 17 hr with actinomycin D (25 microng/ml), adriamycin (40 microng/ml), or puromycin (5 micron/ml) or with 5-fold lower concentrations of these drugs were maximally inhibited (greater than 90%) in their ability to synthesize DNA, RNA, and protein within 1 hr. However, only cells incubated for 17 hr with the high concentrations of drugs showed increased sensitivity to killing by antibody and complement. Line 1 cells incubated with high concentrations of these drugs of 17 hr, washed, and resuspended in drug-free medium recovered their resistance to killing by antibody and complement within 4 hr. These cells ever after culture for 24 hr in drug-free medium did not regain their ability to synthesize DNA, RNA, or protein. A similar lack of correlation between synthesis of these macromolecules and sensitivity to antibody-complement-mediated killing was observed after the cells were treated with physical agents that inhibit macromolecular synthesis. Both heat-treated and X-irradiated cells were inhibited in their ability to synthesize DNA, RNA, and protein immediately after treatment; however, only X-irradiated cells (6 and 16 hr postirradiation) were increased in their sensitivity to antibody-complement-mediated killing. Our data show that the ability of line 1 tumor cells to resist humoral immune attack does not depend solely on their ability to synthesize DNA, RNA, or protein.

Antibodies↗
PubMed1977

Effect of concanavalin A on the killing of tumor cells by antibody and complement.

Concanavalin A (Con A) was found to inhibit the killing of antibody-sensitized line-1 tumor cells (TA) by guinea pig complement (GPC) but not by human complement (HuC). Other plant lectins (wheat germ, leucoagglutinin, and pokeweed mitogen) were also tested but Con A was the only lectin found to inhibit antibody-GPC-mediated killing. The inhibitory effect of Con A was observed when the GPC was mixed with Con A or when the antibody-sensitized cells were pretreated with Con A (TA-Con A) before the addition of GPC. The effect could be reversed by treatment of such cells with alpha-D-methylglucopyranoside or by incubation at 37 degrees C for approximately 2 hr. Con A appeared to act by preventing the binding of the first component of GPC (GPC1) to antibody-sensitized tumor cells. Differences in the binding of the first component of HuC (HuC1) and GPC1 to TA-Con A suggested that a difference in the binding site for HuC1 and GPC1 might exist. There was no difference in the number of GPC1 molecules fixed to antibody-sensitized sheep erythrocytes (EA) or EA treated with Con A in experiments using the same antibody as used with the tumor cells and the same Con A preparation. It would consequently appear that the inhibitory effect of Con A on the binding of GPC1 to TA is not due solely to an interaction of Con A with the antibody.

Animals↗
PubMed1977

Deviated lysis (d.l.): III. Kinetics of interaction of d.l. activity with chicken erythrocytes: evidence for E formation.

The interaction of d.l. activity with chicken red cells (CE) generates a cell intermediate with the properties of classical E*. Generation of CE* by d.l. activity at 37 degrees C is rapid, while there is a considerable lag in the conversion of CE* to ghost and hemoglobin. Conversion of CE* to ghosts can be blocked by high concentration of EDTA and/or 0 degrees C. CE* contain at least C6 and C9 on their surface.

Animals↗
PubMed1977

Effect of concanavalin A on the classical complement pathway.

Lysis of sheep erythrocytes (E) sensitized with anti-Forssman antiserum (EA) is inhibited by the action of concanavalin A (Con A) on whole guinea pig complement (GPC). The degree of inhibition observed for a given quantity of GPC was dependent on the Con A concentration. Specifically, Con A inhibits the activity of the early acting complement components C1 and C2 in the fluid phase, but has no significant effect on lysis once these components are bound to EA. Results of tmax experiments performed in the presence or absence of Con A showed that inhibition of C2 activity results from a direct interaction between Con A and C2 and not from a decreased number of effective EAC14 sites. Furthermore, since Con A pretreated or untreated EAC14 cells had the same tmax value, Con A and C2 apparently do not compete for the same binding site on the indicator cells. The lectin has no observable effect on either fluid phase or cell-bound C4 activity. Under similar conditions, wheat germ or soy bean agglutinin, leucoagglutinin or pokeweed mitogen did not inhibit hemolysis.

Antibodies↗
PubMed1977

Metabolic requirements for hormone-induced resistance to antibody-complement mediated killing of tumor cells.

Line-1 guinea pig hepatoma cells are susceptible to killing by anti-Forssman IgM antibody plus guinea pig complement (GPC). When these tumor cells are incubated with insulin, epinephrine, hydrocortisone, or prednisolone, the cells show a marked reduction in their susceptibility to antibody-C-killing. If the ability of the cells to synthesize DNA, RNA, and protein is impaired by pretreatment with metabolic inhibitors, x-irradiation, or culture in nutrient-deficient media, the hormones are no longer effective in rendering the cells resistant to killing. If only DNA synthesis is impaired, but not RNA and protein synthesis, the hormones are effective. The inability of cells inhibited in their macromolecular synthesis to be rendered resistant to killing after hormone treatment is not due to an inability of the cells to bind hormone.

Amino Acids↗
PubMed1976

Detection of complement-dependent antibody to tumor cells in sera of strain-2 guinea pigs cured of their tumors by BCG Treatment.

Sera of strain-2 guinea pigs (cured of line-10 tumor by BCG therapy) were tested for complement-dependent, cytotoxic antibody. About 30% of the sera tested contained significant cytotoxic acitivity with the addition of human, but not syngeneic, complement. Using papain pretreated line-10 cells, we detected antibody in about 50% of the sera with syngeneic sera as the source of complement. Antibody to line-10 was also demonstrated in selected sera by indirect fluorescence and the C1 fixation and transfer test.

Animals↗
PubMed1976

Regression of established tumors and induction of tumor immunity by intratumor chemotherapy.

The inoculation of a mixture of drugs and guinea pig hepatoma cells (line-10) induced tumor-specific immunity in about 20% of guinea pigs. When guinea pigs with established intradermal tumors were given various drugs ip, no cures were observed; in contrast, multiple intralesional injections of actinomycin D, 1,3-bis(2-chlorethyl)-1-nitrosourea, adriamycin, mitomycin C, and melphalan were effective in curing animals of their intradermal tumors at a time when there were tumor cells in the draining lymph nodes; dimethyl-triazenoimidazole carboxamide, methotrexate, 5-fluorouracil, and 6-mercaptopurine were not effective. More than 80% of the cured animals were immune to rechallenge with 10(6) line-10 tumor cells.

Animals↗
PubMed1976

Persistence of immunoglobulin and complement components C4 and C3 bound to guinea pig tumor cells.

Guinea pig hepatoma cells (line-10) growing as ascites were studied for the presence of immunoglobulin, C4, and C3 (components of complement) on their surfaces. Immunoglobulin, C4, and C3 content increased with length of time spent in the peritoneal cavity. The persistence of these factors bound in vivo or in vitro was also determined. Complement-fixing (CF) activity of cellbound antibody disappeared from the surface more rapidly at 37 degrees C than at 4 degrees C; the continued presence of cellbound immunoglobulin in non-complement-fixing form could be demonostrated at either temperature. No CF activity was released into the medium. C4 and C3 were released into the medium and could be demonstrated in the medium by immunochemical methods.

Animals↗