Biology of disease. Endogenous control of the neoplastic process.
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Biomedical subjects
Publications and source records attributed to M K Robinson.
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Cytolytic T-lymphocytes (CTL) can be repeatedly stimulated in L5178Y cell tumor-dormant DBA/2 mice by the i.p. inoculation of 2 X 10(6) X-irradiated L5178Y cells. The restimulated CTL activity has the same kinetics of generation and decline and the same target cell specificity as does the CTL response generated during establishment of the L5178Y cell tumor dormant state. No increase in adherent cell-mediated cytolytic activity or cytolytic or cytophilic anti-L5178Y antibody can be detected after inoculation of irradiated L5178Y cells. The repeated stimulation of CTL activity in tumor-dormant DBA/2 mice results in the elimination of L5178Y cells from a significant number of tumor-dormant mice.
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The L5178Y-cell tumor dormant state in DBA/2 mice is an excellent model for assessing immunologically mediated tumor-growth restraint mechanisms associated with establishment and control of a tumor dormant state. It has enabled us to relate components of the host's tumor suppressive immune system to the stage of tumor dormancy and the magnitude of the tumor burden. A strong CTL response has been associated with establishment of the tumor dormant state and can be reelicited in vivo or in vitro, after its initial decline, by reexposure to tumor antigen. This reelicitation is mediated via immunologic stimulation of memory CTL. Combined cultures of NAD T-lineage lymphocytes and macrophages from tumor dormant mice produce considerable cytolytic activity where little or no activity can be detected in the individual populations. Based on the similar pattern of tumor target cell specificity of the two responses, it is likely that memory CTL contribute to this synergistic cytolytic activity. The synergistic cytolytic response persists after CTL activity has waned to undetectable levels and is probably the predominant cytolytic activity associated with maintenance of the tumor dormant state. However, this activity may be obscured by proliferation of endogenous tumor cells, which in turn triggers direct macrophage-mediated cytolytic activity. The target cell specificity of this direct macrophage-mediated cytolytic response is also similar to the CTL response suggesting T cell (or memory CTL) involvement in its generation. The L5178Y-cell tumor dormant model is well suited for attempts at cure with immunotherapy. Active specific and nonspecific immunotherapy are each capable of eliminating all tumor cells from approximately 50% of tumor dormant mice. The L5178Y-cell tumor dormant state is one of several animal models of tumor dormancy. The great variety of growth restraint mechanisms that control tumor dormant states in animal systems is strong evidence that tumor dormant states exist in cancer in human beings.
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The rfb locus, determining biosynthesis of O8-specific lipopolysaccharide side chains, was transferred to a rough mutant of Escherichia coli; recombinants producing a complete lipopolysaccharide were more resistant to the complement-mediated bactericidal action of human serum than the rough recipient. Inheritance of the his-linked genes for K27 antigen production did not alter the response to serum. The serum resistance of strains carrying O8 side chains, but not of strains with incomplete lipopolysaccharides, was further increased by inheritance of plasmids R1 and NR1.20
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The integrated rate law for the reaction of the nitrite reductase of Paracoccus denitrificans, a cytochrome cd, has been established for turnover assays using donor ferrocytochromes c and either nitrite or molecular oxygen as the ultimate acceptor. The time course for the concentration of ferrocytochrome follows the law: formula: (see text), where S is the concentration of donor ferrocytochrome c, So is the initial concentration, t is time, and u1, u2, and u3 are empirical parameters that are constant for a given experiment but depend upon the initial substrate concentration. In particular, all the u1 increase with decreasing initial ferrocytochrome concentration. Saturation of reaction rates at high donor ferrocytochrome concentrations was not observed. The parameter u1 was proportional to the enzyme concentration while u2 and u3 were not. The form of the integrated rate law and the behavior of the u1 impose severe restrictions on possible kinetic schemes for the activity of the enzyme. Contemporary mechanisms that have been proposed for mitochondrial oxidase aa3 are examined and found to be inadequate to explain the reactivity of cytochrome cd. The simplest interpretations of the cytochrome cd data suggest that the enzyme does not bind the ferri and ferro forms of donor cytochromes c with equal affinity and that the enzyme is subject to inhibition by a product of reaction. Eucaryotic horse cytochrome c reacts with the Paracoccus cytochrome cd with 77% of the activity when Paracoccus cytochrome c550 is used as the electron donor.
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Bacterial plasmids which contain a copy on TnA are refactory to the uptake of a second by transposition. However plasmids containing two such copies can be constructed by in vitro recombination techniques. Some plasmids containing two copies of TnA have been obtained by conventional transposition, but in all cases they arose by the virtually simultaneous insertion of both units into a replicon that carried no TnA. All stable plamids containing two copies of TnA carried the transposons in opposite orientation.
Plasmids already containing TnA showed decreased susceptibility to the translocation of a further TnA unit when compared with related plasmids that did not contain TnA. The translocation immunity imposed by TnA is exerted only on the plasmid of which it is part. It is suggested that this desensitization by a translocation unit is a general phenomenon that reduces the mutational effects of translocation.
Senior and sophomore baccalaureate nursing students at the University of Kentucky developed a health promotion exposition that targeted college students. This experience gave senior students the opportunity to practice leadership and management skills, such as planning, organizing, collaborating, delegating, evaluating, and time management and conflict resolution. Sophomore students developed teaching abilities, practiced assessment and communication techniques, and increased their knowledge of health-promoting behaviors. Both groups experienced team building and demonstrated accountability. Students reported a positive learning experience that met various course objectives in an innovative way.
Glutathione (GSH) is a potent endogenous antioxidant that protects major organs from oxidant injury. However, present nutrition regimens may inadequately support tissue stores of this tripeptide during critical illness. To determine whether GSH reserves can be enhanced in vivo with intravenous (IV) supplements, rats underwent central venous catheterization, were given chow and water ad libitum during a 2-day recovery period, and were then randomized to receive one of three treatments as an IV bolus: (1) dextrose, (2) glutathione (GSH), or (3) glutathione monoethyl ester. GSH monoethyl ester is transported into cells more easily than is GSH. Tissue and plasma samples were analyzed for GSH at 2 and 4 hours after drug administration. Liver, renal, and ileal mucosal GSH were significantly increased in the GSH-monoethyl ester rats compared with dextrose-treated animals. In addition, plasma GSH was dramatically increased after monoester injection. In contrast, GSH administration depressed liver GSH stores and did not significantly affect GSH concentration in the other organs analyzed. Plasma GSH concentration was elevated 2 hours after GSH administration. We conclude that: (1) the monoethyl ester of glutathione can be used in vivo to enhance tissue and plasma GSH concentration and (2) IV GSH administration does not significantly increase tissue GSH levels and may paradoxically depress hepatic GSH in normal rats. Because the malnourished and critically ill are likely to have depleted GSH stores, nutrition strategies that include the provision of GSH monoester may lend additional support to those organs that are at risk for injury from oxygen free radicals during catabolic states.
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