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Biomedical subjects

J Tosk

Publications and source records attributed to J Tosk.

11 recordsLinked to original sources

Chemiluminescence in a macrophage cell line modulated by biological response modifiers.

We have studied a murine macrophage cell line, J774, and found these cells capable of a zymosan-triggered chemiluminescent oxidative burst. Such activity was enhanced by preincubation with Corynebacterium parvum (CP), bacillus Calmette-Guerin, and lipopolysaccharide (LPS). Under similar conditions, CP and LPS were shown to enhance J774-mediated tumor cell lysis. We have also demonstrated that murine interferon alpha + beta rendered J774 cells more sensitive to the actions of CP and LPS. These results indicate that J774 cells may be useful for the in vitro evaluation of biological response modifiers as well as the study of oxygen radical production by macrophages.

Adjuvants, Immunologic↗

Modulation of hematoporphyrin derivative-sensitized phototherapy with corynebacterium parvum in murine transitional cell carcinoma.

The interaction of photodynamic therapy (PDT) with hematoporphyrin derivative (Hpd) and immunotherapy with Corynebacterium parvum (CP) was studied in a murine transitional cell carcinoma (MBT-2) model. C3H/He mice were transplanted subcutaneously in the hind limb with 2.5 X 10(5) tumor cells. One day after transplantation, mice were randomized into groups to receive saline (control), PDT, CP 25 micrograms, CP 250 micrograms, CP 25 micrograms + PDT, and CP 250 micrograms + PDT. PDT was administered by intraperitoneal (IP) injection of Hpd (12.5 micrograms/g body weight), followed twenty-four hours later by photoirradiation. CP was given intralesionally at the same time as IP injection of Hpd (24 hours before photoirradiation). A low dose of CP (25 micrograms) was shown to enhance the effect of PDT while PDT reduced the benefit obtained with high dose of CP (250 micrograms). In a second series of experiments, CP (250 micrograms) treatment after photoirradiation was shown to give significantly greater benefit than CP treatment before photoirradiation. The study thus indicates that the effectiveness of combined immunophototherapy is dependent on the sequence of the combination and its intricate relationship with the dosage of CP. The enhancement of PDT by low dose of CP in this model suggests the usefulness of this combined immunophototherapy in enhancing tumor control and in lessening deleterious side effects.

Animals↗

Tumor-specific T-lymphocyte cytotoxicity enhanced by low dose of C. parvum.

Three routes of immunotherapy with Corynebacterium parvum (CP) on an ascitic Friend virus-induced leukemia were evaluated. Only the intraperitoneal route, which provided optimal contact between CP and tumor cells, showed prolonged mean survival time. Greatest effectiveness was obtained with multiple injections of CP at weekly intervals and with small initial tumor load. Of particular interest was that lower dosages of CP (5 and 25 micrograms) gave longer protection than dosages of 50 and 250 micrograms. Using in vitro 125I-iododeoxyuridine release assay, these lower dosages were shown to selectively enhance the cytotoxicity associated with T lymphocytes, whereas higher dosages appeared to primarily augment the activity of phagocytes. Moderate natural killer cell activity was observed with both the lower and higher dosages of CP. Data from this study indicate that route of administration, dosage of CP, and size of tumor burden are crucial variables determining optimal response to immunotherapy.

Animals↗

Selenium-induced enhancement of hematoporphyrin derivative phototoxicity in murine bladder tumor cells.

The phototoxicity of hematoporphyrin derivative (Hpd) to murine bladder tumor (MBT-2) cells was studied in vitro. It was observed that selenium in the form of sodium selenite enhanced Hpd-sensitized photodamage in MBT-2 cells under conditions where selenite alone was non-toxic. Sodium selenite enhanced the fluorescence emission of Hpd and augmented the Hpd-sensitized photooxidation of tryptophan. The data suggest that sodium selenite is able to disaggregate Hpd, thereby enhancing Hpd-sensitized phototoxicity.

Animals↗

EEG frequency patterns in the cat prepyriform cortex during sleep and waking.

The cellular populations in the prepyriform cortex are a primary processing station for sensory information from the olfactory bulb. These populations are also influenced from forebrain and other brain systems involved in behaviour. Recording electrodes can be precisely placed in this cortex compared to many other brain structures. This permits straddling the cortical superficial pyramidal cell layer with a bipolar recording configuration and the ability to obtain information about awake-vigilant and other state conditions from this brain structure. Methadone, a vigorously arousing drug in the cat, and a short acting barbiturate was administered to compare the differences of EEG patterns obtained during normal awake and sleep conditions. Fourier analysis was used in this study and combined with computer profiles of spectra to show time relationships of the state conditions in the cortex. Good separation of the spectra, between the major states in the cat, were observed using this technique for both natural and drug-induced changes.

Animals↗

Hydrazines as mutagens in a histidine-requiring auxotroph of Salmonella typhimurium.

Hydrazines have been found naturally in tobacco and mushrooms. Other hydrazines are used in industry, medicine, and agriculture. Although about 38 hydrazines are carcinogenic, few, if any, have been tested successfully in rapid bacterial mutagenesis assays. We have utilized a tester strain of Salmonella typhimurium (TA1530) in order to determine the mutagenic activity of a number of hydrazines and related compounds. This strain is thus shown to be effective as a tester organism for the facile detection of hydrazines as mutagens.

Dose-Response Relationship, Drug↗

Comparison of the metabolic profiles of benzo[alpha]pyrene obtained from primary cell cultures and subcellular fractions derived from normal and methylcholanthrene-induced rat liver.

Hepatocyte primary cell (HPC) cultures derived from either (a) non-induced (normal) or (b) methylcholanthrene (MC)-induced rat liver actively metabolized the carcinogen benzol[alpha]pyrene (BaP) over a 24-h period. In both cases, the BaP metabolites generated were qualitatively similar to those seen in the metabolism of BaP by isolated rat liver microsomal fractions; in addition, unidentified compounds were evident in the chromatographic profile generated by the cultured cells. In cells derived from (a), levels of known metabolites (phenols and diols) increased over the time period studied. On the other hand, in cells derived from (b), levels of diols decreased markedly after 8 h. These results suggest that induction with MC enhances both activation and, to a greater extent, conjugative-detoxification pathways of BaP, so that in cells obtained from (b) the formation of water-soluble metabolites is enhanced and levels of organic soluble metabolites are lower than in cells obtained from (a). Metabolism of BaP in primary cell culture derived from rat liver is thus seen to be similar to in vivo metabolism of the carcinogen, but somewhat in contrast to the in vitro microsomal (subcellular) metabolism of BaP where conjugative-detoxification pathways are virtually inoperative.

Animals↗