Search PubMed⌕ Search

Biomedical subjects

G Wolberg

Publications and source records attributed to G Wolberg.

At least 37 records · Page 2Linked to original sources
PubMed1983

In vivo and in vitro antitumor activity expressed by cells of concomitantly immune mice.

Growth of a primary tumor is often accompanied by the development of resistance to subsequent challenge implants of the same tumor, i.e., concomitant immunity. Using the P815 mastocytoma tumor, the kinetics of concomitant immunity was found to be governed by duration of exposure to the tumor and tumor mass. By implanting small "challenges" prior to the immunizing tumor, resistance to the growth of existing tumor foci was demonstrated. Winn-type assays revealed that antitumor activity was present in cell populations from the peritoneal exudate and lymph node draining the tumor. Peritoneal exudate cells, when infused systemically, were also able to confer protection against P815 mastocytoma challenge, suggesting their role as mediators of concomitant immunity. The 51Cr release technique indicated that cytolytic activity in lymph node cells, peritoneal exudate cells, and the spleen was present over a time course parallel to the kinetics of in vivo challenge. The peritoneal resident cell population was only slightly active; thus, effectors accumulated in the inflammatory exudate. Removal of specific subsets of cells from effector populations with antibody to surface markers and complement produced similar effects on both Winn and cytolytic assays. Anti-Thy 1.2 ablated measurable activity. It was substantially but not completely reduced by anti-Lyt 1.1 and only to a small degree by anti-Lyt 2.1.

Animals↗
PubMed1982

Effect of acyclovir on various murine in vivo and in vitro immunologic assay systems.

In two in vitro tests, lymphocyte-mediated cytotoxicity and neutrophil chemotaxis, acyclovir showed no inhibitory effects at concentrations as high as 600 microM. The compound inhibited rosette formation with nonimmune mouse lymphocytes in vitro by approximately 50 percent at 15.8 microM. The significance of this inhibition is unclear. In four in vivo tests in mice which measured humoral and cell-mediated immunity (complement-dependent cellular cytotoxicity, complement-independent cellular cytotoxicity, delayed hypersensitivity and graft versus host reaction) acyclovir showed no inhibitory effects at single doses up to 200 mg/kg given on day 2 after antigenic stimulation. Four daily doses of acyclovir at 50 mg/kg per day had no effect on the numbers of hemolytic IgM antibody-forming cells in the spleen when assayed on day 4. At the higher dosage of 100 mg/kg per day for four days, there was a slight reduction in the numbers of these cells. There was no significant decrease in hemagglutinin or hemolysin antibody titers after four daily doses of acyclovir up to 200 mg/kg.

Acyclovir↗
PubMed1982

Immune reaction of tumor-bearing mice to Propionibacterium acnes and the antitumor effect of the bacteria.

The relationship between immunological reaction to Propionibacterium acnes (PA) and the antitumor effect of the injected bacterium was investigated. The aim was to determine whether the strength of the immune reaction to the bacterium can be used to predict its antitumor effectiveness. C3Hf/Sed mice received SC injections (right thigh) of viable cells of a methylcholanthrene-induced fibrosarcoma. When the tumor grew to 5 mm, the hosts received 350 micrograms PA IV as the antitumor treatment. Cellular immunity (footpad test) to PA was assayed in one group of these mice 14 days later, and in the other anti-PA agglutinins were determined 28 days later. The PA injection cured 22 of 58 mice in the first, and 20 of 46 mice in the second group. Footpad reaction and agglutinin titers to PA in cured mice were not statistically different from those in mice eventually killed by the tumor. Therefore, the strength of the immune reaction to PA in tumor-bearing mice could not be used to predict the antitumor effectiveness of the bacterium.

Animals↗
PubMed1982

Immunosuppressive effects of the S-adenosylhomocysteine hydrolase inhibitor, 3-deazaadenosine.

Immunosuppressive effects of 3-deazaadenosine (3-DAA), an inhibitor of S-adenosylhomocysteine hydrolase, were tested in vivo in immune assays against sheep red blood cells (SRBC), involving serum titrations for hemagglutinins and hemolysins, cellular cytotoxicity tests and the direct plaque-forming cell assay. At daily doses up to 100 mg/kg, the compound was suppressive when injected before antigen and the effect appeared to be dose-dependent (ED50 = 52.6 +/- 4.9 mg/kg). When doses of 25 mg/kg of 3-DAA were given before antigen, co-injections of 250 mg/kg of L-homocysteine (L-HC) potentiated the suppressive effect, although L-HC alone was inactive. Daily administration of 100 mg/kg of 3-DAA or 250 mg/kg of L-HC alone was not suppressive when given after the antigen; however, in combination they were able to induce suppression. The possible biochemical mechanisms of the suppression, particularly those involving the inhibition of S-adenosylmethionine-dependent methylation reactions, are discussed.

Adenosylhomocysteinase↗
PubMed1982

Inhibition of lymphocyte-mediated cytolysis and cyclic AMP phosphodiesterase by erythro-9-(2-hydroxy-3-nonyl)adenine.

The adenosine deaminase (ADA) inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), at low concentrations (less than 10 microM), enhances the inhibitory activity of adenosine against lymphocyte-mediated cytolysis (LMC) without itself being inhibitory. At higher concentrations, EHNA alone is inhibitory to LMC with an IC50 of 160 microM. This inhibition is reversible upon washout, appears to affect an early stage of the lytic process, and does not appear to involve changes in basal levels of cyclic AMP (cAMP), ribonucleoside 5'-triphosphate pool sizes, S-adenosylhomocysteine levels, or protein carboxymethylation. EHNA does enhance the cAMP response of cytolytic lymphocytes (CL) to activators of adenylate cyclase such as prostaglandin E1. EHNA inhibits lymphocyte high-affinity cAMP phosphodiesterase at immunosuppressive levels, exhibiting hyperbolic mixed-type inhibition (Ki = 83 microM, alpha = 0.47, beta = 0.18). Whereas inhibition of intralymphocytic ADA is complete at low concentrations (less than 25 microM) of EHNA, inhibition of LMC and intralymphocytic cAMP phosphodiesterase increases linearly with EHNA concentration to at least 200 microM. The presence of 200 microM EHNA during the centrifugation of mixtures of CL and EL4 leukemia target cells leads to increased CL cAMP levels. 2'-Deoxycoformycin, a more potent ADA inhibitor than EHNA, is not inhibitory to LMC and shows none of these cAMP-related effects. These results suggest that CL-target cell contact stimulates adenylate cyclase in the CL and that EHNA inhibits LMC due to its enhancement of this target cell-stimulated elevation of cAMP.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1981

In vitro cytotoxicity expressed by cells active against established tumors in vivo.

Although antitumor activity by host cells has been documented in vivo and in vitro, the cellular relationships between these two classes of studies are not clear. Cells capable of causing the regression of solid tumors are generated in lymph nodes draining sites of immunization with Corynebacterium parvum:irradiated P815 mastocytoma admixtures. These cells are active in a 51Cr release assay at a low effector:target ratio producing a characteristic low level of specific 51Cr release which required 24 hr for optimal development. The activity is immunologically specific for the immunizing tumor and is mediated by nonadherent, rapidly dividing (vinblastine-sensitive) cells. They are absent in thymectomized animals and susceptible to alpha-Thy 1.2 antibody and complement. They are present in peritoneal exudates, consistent with the systemic resistance demonstrable in the animal model. The properties and development kinetics of effector cells measured by 51Cr release correlate closely with those of cells showing in vivo activity, supporting the identity of the two populations.

Animals↗
PubMed1980

Adenosine analogues as substrates and inhibitors of S-adenosylhomocysteine hydrolase in intact lymphocytes.

A number of adenosine analogues have been examined for their ability to interact with S-adenosyl-L-homocysteine (SAH) hydrolase in intact mouse lymphocytes. In the presence of erythro-9-(2-hydroxy-3-nonyl)adenine, 3-deazaadenosine, 8-azaadenosine, formycin A, 2-aminoadenosine, 2-fluoroadenosine, N6-methyladenosine, N6-hydroxyadenosine, purine ribonucleoside and inosine were each metabilized to radioactive analogues of SAH when cells were labeled with either L-[2-3H]methionine or L-[35S]homocysteine. Tubercidin was shown to undergo metabolism both to S-[3H]tubercidinyl-L-methionine and to S-[3H]tubercidinyl-L-homocysteine in cells labeled with [2-3H]methionine. 9-beta-D-Arabinofuranosyladenine and 2'-deoxyadenosine caused marked elevations of [3H]SAH in cells preloaded with [2-3H]methionine but were not themselves metabolized detectably to SAH analogues. Adenine and 5'-deoxyadenosine also caused substantial elevations of [3H]SAH under these same conditions. Some of the adenosine analogues shown to be metabolized to SAH analogues also caused an elevation of SAH in the lymphocytes. These results indicate the potential of adenosine analogues to interfere with cellular methylation reactions due either to their inhibition of SAH hydrolase or to their metabolism, via this enzyme, to SAH analogues.

Adenosine↗
PubMed1980

Modulation of cyclic AMP metabolism by S-adenosylhomocysteine and S-3-deazaadenosylhomocysteine in mouse lymphocytes.

Mouse lymphocytes incubated with micromolar concentrations of adenosine or 3-deazaadenosine, in medium supplemented with L-homocysteine, rapidly accumulated supramillimolar concentrations of S-adenosylhomocysteine (AdoHcy) or S-3-deazaadenosylhomocysteine (c3AdoHcy), respectively. Lymphocytes thus preloaded with high levels of AdoHcy or c3AdoHcy exhibited markedly enhanced (5- to 40-fold) cyclic AMP responses to prostaglandin E1, adenosine, 2-chloroadenosine, isoproterenol, and cholera toxin. This enhancement of cyclic AMP response by intracellular AdoHcy or c3AdoHcy was attributable both to amplification of the activity of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] and to inhibition of cyclic AMP phosphodiesterase (3',5'-cyclic-nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17). Basal and prostaglandin E1- and isoproterenol-stimulated activities of adenylate cyclase, assayed in lymphocyte homogenates, were increased 1.3- to 2.0-fold after treatment of the cells with homocysteine plus either adenosine or 3-deazaadenosine. AdoHcy and c3AdoHcy were found to be competitive inhibitors (with Ki values of 1.7 and 4.8 mM, respectively) of the high-affinity cyclic AMP phosphodiesterase present in lymphocyte homogenates. It is evident, therefore, that increased cellular levels of AdoHcy or c3AdoHcy can affect cellular physiology via perturbation of cyclic AMP metabolism as well as via inhibition of S-adenosylmethionine-dependent methylation reactions.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1978

Inhibition of lymphocyte-mediated cytolysis by 3-deazaadenosine: evidence for a methylation reaction essential to cytolysis.

3-Deazaadenosine (deazaAdo) inhibits lymphocyte-mediated cytolysis in vitro at micromolar concentrations and is potentiated markedly in this activity by L-homocysteine thiolactone. DeazaAdo alone causes a rapid, dose-dependent buildup of S-[(3)H]adenosylhomocysteine (AdoHcy) and S-[(3)H]adenosylmethionine in cytolytic lymphocytes labeled with L-[2-(3)H]methionine; smaller amounts of S-3-[(3)H]deazaadenosylhomocysteine (deazaAdoHcy) are also formed in these cells. The simultaneous addition of deazaAdo and L-homocysteine thiolactone to the lymphocytes results in a massive intracellular accumulation of deazaAdoHcy. Both the inhibition of lymphocyte-mediated cytolysis and the cellular accumulation of [(3)H]AdoHcy caused by deazaAdo alone are reversed rapidly by removal of drug from the medium. However, the inhibition of cytolysis and the large cellular buildup of deazaAdoHcy resulting from treatment of the lymphocytes with deazaAdo plus L-homocysteine thiolactone are dissipated more slowly under these same conditions. Unlike adenosine, deazaAdo is not potentiated in its inhibition of lymphocyte-mediated cytolysis by Ro 20-1724 [4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone], an inhibitor of cyclic AMP phosphodiesterase, and has little or no effect upon the level of lymphocytic cyclic AMP. DeazaAdo is not metabolized detectably to 5'-nucleotides in the lymphocytes and does not cause a decrease in the pool sizes of CTP, UTP, ATP, or GTP. Both AdoHcy and deazaAdoHcy have been reported to be powerful inhibitors of a variety of S-adenosylmethionine-utilizing methyltransferases. The present results, therefore, indicate that the effect of deazaAdo upon lymphocyte-mediated cytolysis is due ultimately to the inhibition of an unidentified but crucial methyltransferase within the cytolytic lymphocytes and provide an insight into the biochemical processes involved in lymphocyte-mediated cytolysis.

Cyclic AMP↗
PubMed1977

Antibody to Corynebacterium parvum in normal human and animal sera.

Using a microtiter bacterial agglutination test, we have estimated antibodies to Corynebacterium parvum in "normal" human and "normal" and immune animal sera. Widely differing levels of C. parvum antibodies were found in the normal human sera. The median titer for all 310 human sera was 1:128, whereas that for the 1- to 17-year and 18- to 50-year subgroups was 1:64 and 1:512, respectively. Antibody titers in the various animal species were generally much lower.

Adolescent↗