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Biomedical subjects

M S Meltzer

Publications and source records attributed to M S Meltzer.

At least 163 records · Page 9Linked to original sources

Tumor regression after intralesional injection of emulsified trehalose-6,6'-dimycolate (cord factor): efficacy increases with oil concentration.

Injection of emulsified trehalose-6,6'-dimycolate (TDM), a mycobacterial glycolipid, into transplants of an established, syngeneic murine fibrosarcoma induced complete regression of tumor in a number of animals. The number of animals in wich tumor regressed completely depended on the amount of oil in the emulsion. The anti-tumor activity of the TDM emulsion containing the highest concentration of oil was equivalent to that of living BCG.

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Bidirectional amplification of macrophage-lymphocyte interactions: enhanced lymphocyte activation factor production by activated adherent mouse peritoneal cells.

Adherent peritoneal cells (90 to 95% macrophages) from mice injected with Mycobacterium bovis, strain BCG, or certain noninfectious agents such as pyran copolymer or phytohemagglutinin showed increased chemotactic and tumoricidal capacity in vitro. These activated macrophages elaborated 2 to 5 times more lymphocyte-activating factor (LAF) in vitro than equal numbers of adherent cells from untreated mice. In contrast, adherent PC from mice treated with thioglycollate or mineral oil were not cytotoxic and did not produce more LAF than PC from untreated mice. Adherent PC from untreated nude mice, which have increased chemotactic and tumoricidal capacity in vitro, also exhibited enhanced LAF production compared to adherent PC from their normal littermates. Increased production of LAF was also evident with adherent PC and the macrophage-like tumor cell line P388D1 after incubation in vitro with bacterial endotoxins or with antigen-induced lymphokines. These data indicate that adherent PC can be activated either in vivo or in vitro to elaborate more LAF. Thus, activated macrophages are more effective than normal macrophages in amplification of the afferent limb of immune responses as well as in their effector functions.

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Macrophage activation for tumor cytotoxicity: induction of tumoricidal macrophages by supernatants of PPD-stimulated Bacillus Calmette-Guérin-immune spleen cell cultures.

Resident peritoneal macrophages from normal mice were activated for tumor cytotoxicity in vitro by co-cultivation with BCG1-immune spleen cells and PPD and by incubation with supernatants of PPD-stimulated BCG-immune spleen cell cultures (lymphokine supernatants). Lymphokine activation of macrophages occurred in unfractionated PC suspensions as well as in macrophage monolayers depleted of nonadherent PC. Tumor cytotoxicity by lymphokine-activated macrophages was evident by 3 to 4 hr of culture in active supernatants, reached maximal levels by 8 to 12 hr. and was absent by 20 hr. Continued incubation in lymphokines or even re-exposure after washing did not maintain macrophage cytotoxicity. The capacity of normal resident macrophages to be activated by lymphokines in vitro progressively decreased and was absent by 20 hr in culture. This decrease did not necessarily reflect cell death; macrophage viability as estimated by exclusion of trypan blue or by phagocytic responses did not change over the 20-hr culture period. The short lived nature of both macrophage tumoricidal capacity and capacity of precursor cells to be activated by lymphokines may function as negative feedback mechanisms in immune reactions.

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Characterization of macrophage chemotaxins in tumor cell cultures and comparison with lymphocyte-derived chemotactic factors.

Culture fluids from five murine sarcomas were chemotactic for syngeneic peritoneal macrophages in vitro. Peritoneal macrophages from mice infected with Mycobacterium bovis, strain Bacillus Calmette-Guérin, were more responsive to the chemotactic factor in tumor cultures than were normal macrophages. Peritoneal granulocytes, however, did not significantly respond to this factor. The level of chemotactic activity in tumor cultures paralleled cell growth for all five tumors; maximal levels occurred during log growth. Culture medium alone or fluids from proliferating spleen cell cultures stimulated with mitogens did not have detectable chemotactic activity. Chromatography of the tumor culture fluids resulted in a single peak of chemotactic activity in the 15,000-molecular weight range on Sephadex G-100 and at about 7.5 mmho/cm specific conductance on diethylaminoethyl cellulose. By both biological and physicochemical characteristics, the chemotactic activity in tumor culture fluids was different from mouse lymphocyte-derived chemotactic factor.

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Suppression of tumor growth in strain 2 guinea pigs by xenogeneic antitumor antibody.

Line 10 hepatoma cells were incubated with antiserum specific against line 10 cells (RaL10) and then tested for growth in syngeneic Wright strain 2 guinea pigs. Palpable tumors appeared in only 11 of 23 animals inoculated id with 10(5) RaL10-treated tumor cells, compared with an incidence of 21 of 23 for nonimmune rabbit serum (NRS)-treated cells and 23 of 23 for cells treated with syngeneic guinea pig serum. Animals inoculated with RaL10-treated tumor cells did not develop systemic tumor immunity. The long-term survival of guinea pigs receiving RaL10-treated tumor cells iv was 6 of 12 with a dose of 10(5) cells and 8 of 11 with 10(4) cells. None of the animals receiving 10(4) or 10(5) control tumor cells treated with NRS survived. RaL10 antiserum was not toxic to line 10 tumor cells in vitro, but mediated tumor-specific cytolytic reactions in the presence of fresh guinea pig serum or on the addition of peritoneal exudate cells from nonimmunized syngeneic guinea pigs.

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Depressed chemotactic responses in vitro of peritoneal macrophages from tumor-bearing mice.

The in vitro chemotactic responses of peritoneal macrophages from mice bearing transplantable syngeneic 3-methylcholanthrene-induced tumors in their footpads were depressed to about 50% of normal levels. This chemotactic defect to both lymphocyte- and complement-derived stimuli was evident before the appearance of palpable tumor (within 1 week of tumor injection) and persisted until the death of the animal by 6-8 weeks. Chemotactic depression was not observed with macrophages from mice treated with tissue culture medium, fetal calf serum, incomplete Freund's adjuvant, or syngeneic spleen cells.

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Interaction of BCG-activated macrophages with neoplastic and nonneoplastic cell lines in vitro : quantitation of the cytotoxic reaction by release of tritiated thymidine from prelabeled target cells.

Peritoneal cells from mice infected ip with Mycobacterium bovis, strain BCG, were cytotoxic to syngeneic tumor cells in vitro. Cytotoxicity was estimated by measurement of release of tritiated-thymidine (3-H-TDR) from prelabeled target cells. The cell responsible for tumor cytotoxicity was the macrophage. Macrophages from uninfected mice or from oil-, starch-, or thioglycollate-induced peritoneal exudates had little effect on labeled tumor monolayers. Tumoricidal macrophages were present at 3-7 days and persisted through 6 weeks after a single BCG injection. Two neoplastic/nonneoplastic cell-line pairs, all four of the cell lines derived from a cloned syngeneic embryo cell line, were used as target cells for BCG-activated macrophages. Both tumor cell lines released significantly more 3-H-TDR than did the two nonneoplastic lines. In a mixed neoplastic/nonneoplastic target cell population, BCG-activated macrophages selectively destroyed the neoplastic cells; nonneoplastic cells were not affected as "innocent bystanders".

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Protective tumor immunity induced by potassium chloride extracts of guinea pig hepatomas.

Tumor-specific antigens of cells of the diethylnitrosamine-induced hepatomas in strain-2 guinea pigs were extracted with 3 M KCl. Immunization of normal animals with the extracted tumor antigens in adjuvant protected them against a subsequent challenge with viable tumor cells. Extracted tumor-specific antigens were less effective immunogens than viable tumor cells for both of two antigenically distinct lines.

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Differential cytotoxicity of tumorigenic and nontumorigenic strain-2 guinea pig cells as mediated by syngeneic phytohemagglutinin-stimulated peritoneal exudate cells.

Phytohemagglutinin (PHA)-stimulated peritoneal exudate (PE) cells from strain-2 guinea pigs were more cytotoxic in culture to syngeneic tumorigenic cells than to syngeneic nontumorigenic cells. Cytotoxicity was measured by the release of 3H-thymidine from prelabeled target cells. Tumor-producing guinea pig fetal cells transformed in culture by chemical carcinogen released up to 70 percent of their label in the presence of PHA-stimulated PE cells. Non-tumor-producing cells, regardless of their morphologic characteristics, were less affected by PHA-stimulated PE cells. Nontumorigenic cultures included untreated early passage and long-term cultures previously treated with a carcinogenic or noncarcinogenic chemical. Differential cytotoxicity to tumorigenic cultures were best distinguished from nontumorigenic cultures when 0.5-1 times 10-6 PE cells and 50-100 mug PHA were incubated with 1 times 10-4 3H-thymidine-labeled target cells for 48 hours.

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Mouse mononuclear cell chemotaxis: description of system.

The mononuclear cell chemotaxis assay was adapted for use with normal mouse peritoneal cells. Mouse peritoneal macrophages responded well to endotoxinactivated mouse serum and to chemotactic factors produced by mouse spleen cell cultures stimulated with mitogens or specific antigen. The assay was quantitative, reproducible, and applicable to several mouse strains.

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Mouse mononuclear cell chemotaxis. I. Differential response of monocytes and macrophages.

The chemotactic responses of peripheral blood monocytes and peritoneal macrophages to lymphocyte- and complement-derived stimuli were studied in vitro. Monocyte and macrophage chemotactic responses to these stimuli were different in both dose-response and time course. These differences provide a useful functional marker between these two cell populations.

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