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Biomedical subjects

R M Schultz

Publications and source records attributed to R M Schultz.

At least 235 records · Page 13Linked to original sources
PubMed1979

Animal models in cancer research which could be useful in studies of the effect of alcohol on cellular immunity.

Alcohol appears to exert a depressive effect on host immunity. Animal models useful in studying immune responsiveness in cancer research are discussed, which could be of value in studying the effect of alcoholism. Allogeneic tumor grafts are poorly rejected in immunosuppressed mice. Of the four major cellular elements of the immune system, the macrophage appears to have a critical role in immune surveillance. Several conditions occur which abrogate or restrict the tumoricidal activity of macrophages. Stress induced by physical restraint results in depressed macrophage activation. The tumoricidal activation induced in macrophages by interferon was markedly depressed in the presence of the corticosteroids, hydrocortisone, prednisone, and dexamethasone. In addition, prostaglandins (PGE1 and PGE2) also were found to decrease interferon activation of macrophages. Since immune deficiency is a trait of alcoholism and cancer, animal models with defined, measurable, immunological parameters would be useful in studying the effect of alcohol on cellular immunity.

Adrenal Cortex Hormones↗
PubMed1978

Regulation of macrophage tumoricidal function: a role for prostaglandins of the E series.

Exogenously added prostaglandins E1 and E2, but not F2alpha, inhibited the tumoricidal activity of interferon-activated macrophages of mice. A role for adenosine 3',5'-monophosphate (cyclic AMP) in modulating macrophage functional activity was suggested because prostaglandins of the E series increase intracellular concentrations of cyclic AMP in macrophages and because treatment of interferon-activated macrophages with dibutyryl cyclic AMP consistently inhibits expression of cytotoxicity. Since the activated macrophage releases high concentrations of prostaglandin E2, it is postulated that this prostaglandin could act locally in negative feedback inhibition to limit cell activities.

Animals↗
PubMed1978

The mechanism of action of ethanolamine ammonia-lyase, an adenosylcobalamin-dependent enzyme. Reaction of the enzyme.cofactor complex with 2-aminoacetaldehyde.

Ethanolamine ammonia-lyase (EC 4.3.1.7) catalyzes the adenosylcobalamin-dependent deamination of ethanolamine and 2-aminopropanol. Incubation of the enzyme.cofactor complex with 2-aminoacetaldehyde leads to rapid cleavage of the carbon--cobalt bond accompanied by the destruction of the corrinoid portion of the cofactor. During this reaction the adenosyl portion of the cofactor is oxidized to 4',5'-anhydroadenosine, and the aminoacetaldehyde is converted to acetic acid, which remains associated with the enzyme as a noncovalent complex which survives gel filtration. There is no evidence for the alkylation of the corrin metal by the substrate analog. The enzyme.AdoCbl complex is thus able to eliminate an amino group from a substrate analog without the formation of a new alkyl cobalamin in which the analog is a ligand. These observations do not support the participation of what might be termed "substratylcobalamin" as an intermediate in the ammonia migration occurring in reactions catalyzed by ethanolamine ammonia-lyase.

Ammonia-Lyases↗
PubMed1978

Absolute rates of protein synthesis during meiotic maturation of mammalian oocytes in vitro.

Measurements of the rates of incorporation of [35S]methionine into protein and the specific activities of endogenous free methionine pools have been used to calculate the absolute rates of protein synthesis in mouse oocytes during spontaneous meiotic maturation in vitro. Fluorodinitro[3H]benzene was used to determine the specific activity of the oocyte's free methionine pool. It was found that the absolute rate of protein synthesis decreased from 43 to 31 pg/hr per oocyte during meiotic progression from dictyate to metaphase II (meiotic maturation), while the size of the intracellular free methionine pool decreased from 61 to 35 fmol per oocyte during the same period. Comparable measurements made on ovulated mouse oocytes that had undergone meiotic maturation in vivo strongly suggest that the decrease in the absolute rate of protein synthesis observed during meiotic maturation in vitro is physiologically significant. An alternative method that depends upon differential expansion of the oocyte's endogenous methionine pool was also used to determine absolute rates of protein synthesis. The results of these experiments are in excellent agreement with those obtained by using fluorodinitro[3H]benzene, indicating that the oocyte's free methionine pool is not compartmentalized.

Animals↗
PubMed1978

Meiotic maturation of mouse oocytes in vitro: protein synthesis in nucleate and anucleate oocyte fragments.

Nucleate and anucleate fragments of mouse oocytes have been isolated following treatment of fully grown oocytes with cytochalasin B. The nucleate oocyte fragments resume meiosis in vitro, progressing from dictyate of the first meiotic prophase to metaphase II ('meiotic maturation'), and exhibit all of the changes in protein synthesis normally associated with meiotic maturation of mouse oocytes. The anucleate oocyte fragments also undergo certain of the changes in protein synthesis associated with meiotic maturation, despite the absence of nuclear progression. These results suggest that the acquisition of meiotic competence (i.e. the ability to undergo meiotic maturation) during growth of the mammalian oocyte is due to changes in the quality, rather than the quantity, of cytoplasm and that the reprogramming of protein synthesis during meiotic maturation is directed by RNA templates already present in the cytoplasm. The behaviour of anucleate oocyte fragments is discussed in terms of the proposed role for nucleoplasm in the initiation of changes in protein synthesis during meiotic maturation of mouse oocytes.

Animals↗
PubMed1978

Macrophage activation and antitumor activity of a Brucella abortus ether extract, Bru-Pel.

Bru-Pel and Brucella abortus lipopolysaccharide (LPS) were tested for both macrophage activation and antitumor activity in an artificial metastasis model. Resting macrophages were rendered nonspecifically tumoricidal for MBL-2 lymphoblastic leukemia target cells by exposure to Bru-Pel at greater than or equal to 1 ng/ml of culture medium. B. abortus LPS failed to activate macrophages in vitro at all concentrations tested. Ip treatment of homozygous nude mice with Bru-Pel induced cytotoxic macrophages, indicating that Bru-Pel activated macrophages through a thymic-independent process. An artificial metastasis model was developed where single-cell suspensions of Madison 109 lung carcinoma were inoculated iv into syngeneic BALB/c mice. Bru-Pel, but not B. abortus LPS, strikingly inhibited tumor-colony formation in the lungs. Although Bru-Pel contains endotoxin, the data demonstrate that endotoxin is apparently not the active component by which Bru-Pel activates macrophages and enhances host resistance to cancer.

Animals↗
PubMed1978

Similarities among factors that render macrophages tumoricidal in lymphokine and interferon preparations.

Lymphokine preparations, including supernatants derived from antigen-stimulated Bacillus Calmette-Guérin-immune spleen cell cultures and normal spleen cells incubated with insoluble concanavalin A, were compared with partially purified L-cell interferon for the ability to render resting macrophages nonspecifically tumoricidal in vitro. Significant activation of macrophages by lymphokine preparations occurred at concentrations as low as 0.5 and 0.25% of the assay mixture for antigen-stimulated and concanavalin A-induced lymphokine, respectively. These end point concentrations were each determined to contain 0.3 unit of interferon per ml. Supernatants obtained from unstimulated normal spleen cells, concanavalin A-treated nu/nu spleen cells, or Bacillus Calmette-Guérin-immune spleen cells in the absence of sensitizing antigen did not enhance macrophage tumoricidal function and lacked interferon. Activation by L-cell interferon required at least 1 unit/ml. The macrophage-activating factors contained in lymphokine and interferon preparations were stable at pH 2 and at 56 degrees, but they were destroyed when heated at 80 degrees for 30 min, and were inactivated by trypsin. The data demonstrate common properties for the induction of tumoricidal macrophages by these divese preparations.

Animals↗
PubMed1978

Chemical and biological adjuvants capable of potentiating tumor cell vaccine.

With an L1210 tumor vaccine model, three biological and two chemical agents were tested for their ability to act as adjuvants. Adjuvant was administered with irradiated L1210 cells to immunize mice against this poorly immunogenic tumor. Two chemicals, pyran copolymer and glucan, and one biological, Brucella abortus strain 456 ether extract, were shown to be strong stimulators of antitumor immunity. Vaccination with irradiated tumor cells or adjuvant alone did not produce host resistance. Optimal immunity to challenge was produced by concomitant administration of either pyran copolymer, glucan, or B. abortus strain 456 ether extract with L1210 vaccine. Antitumor immunity was maximally expressed when vaccine and adjuvant were administered i.p. Evidence for systemic immunity was demonstrated when challenge was at a distal s.c. site. Mice immune to challenge were found to be refractory to a later rechallenge.

Adjuvants, Immunologic↗
PubMed1978

Effect of maleic anhydride-divinyl ether copolymers on experimental M109 metastases and macrophage tumoricidal function.

Pyran copolymer (NSC-46015) was compared with five maleic anhydride-divinyl ether copolymers (MVEs) of narrow molecular weight range both for the ability to render macrophages nonspecifically tumoricidal and to retard the development of artificially induced metastases. All MVEs were found effective at activating macrophages in vivo, although the optimal dose for each varied. No correlation was obtained between intrinsic viscosity and degree of activation. Pyran was found to strikingly inhibit M109 pulmonary metastases formation when given over a period of 5 days prior to, or 1 day after, iv tumor inoculation. Histologically, tumor inhibition appeared to result from macrophage accumulations and histiocytic granulomas in the lung. Generally, when MVEs were compared in the artificial metastasis model, polymers with the lower molecular weights were the most active.

Animals↗
PubMed1978

Cell and tissue distribution of 14C-labeled pyran copolymer.

The tissue distribution of pyran (maleic anhydride-divinyl ether) copolymer was studied after a single ip injection of 14C-labeled pyran (25 mg/kg) to mice. The pyran showed a reticuloendothelial distribution with the liver and spleen containing the highest concentrations which persisted for at least 21 days after drug treatment. Blood levels of 14C-pyran reached a peak 2 hours after injection and were cleared within 6 hours. Attempts to measure uptake of 14C-pyran by peritoneal macrophages were unsuccessful due to an inability to recover macrophages between 3 and 24 hours after ip pyran administration. Since activated macrophages appear to be the primary mechanism by which pyran enhances host resistance to microbial infection and neoplasia, the uptake of 14C-pyran by isolated peritoneal macrophages in vitro was studied. Purified macrophages showed a gradually increasing uptake of 14C-pyran, and a large amount of cell-associated radioactivity was bound to trichloroacetic acid-precipitable material. Several polyanions, including unlabeled pyran, dextran sulfate, and poly(I)-poly(C), competed for acid-precipitable receptor molecules. The superior antitumor effects of pyran as compared to other polyanions may result from the continuous presence of the synthetic polymer in the host. Possible mechanisms of immunopotentiation by pyran are discussed.

Animals↗
PubMed1978

Cytotoxic activity of interferon-treated macrophages studied by various inhibitors.

The ability of interferon-treated macrophages to kill or inhibit the growth of tumor cells is markedly influenced by the local environment. The macrophage cytotoxic effector system is regulated by serum and other environmental factors that suppress tumor killing. Prostaglandins E1 and E2, but not F2alpha reversibly inhibited the tumoricidal state of interferon-treated macrophages. Hydrocortisone was similarly active at suppressing macrophage function. Such nonimmunologically derived factors could prevent the final triggering step for macrophage-mediated tumor killing in the local environment of the tumor and may be important in the pathogenesis of progressive tumor growth.

Animals↗
PubMed1977

Interferon: an inducer of macrophage activation by polyanions.

Purified mouse fibroblast interferon (IF) directly rendered resting macrophages tumoricidal. The physicochemical properties and species specificity of the stimulatory agent fall within the present definition of IF. Since a number of polyanions induce macrophage IF, the antitumor and antimicrobial activities may result from the ability of newly released IF to modify macrophage activity.

Animals↗