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11.
Summary We determined whether the systemic administration of viable Mycobacterium bovis organisms (BCG) or a lipophilic derivative of muramyl tripeptide (MTP-PE) would lead to the activation of antitumor properties in murine Kupffer cells (KC). KC-mediated tumor cytolysis was determined by the release of radiolabeled nuclear breakdown products of target cells. KC harvested from either C57BL/6 or C3H/HEN mice treated with saline exhibited no cytotoxicity against syngeneic B16 melanoma or UV-2237 fibrosarcoma cells. In contrast, KC harvested from BCG or MTP-PE-injected mice were highly cytotoxic against the tumor targets, as measured by an in vitro radiorelease assay. The demonstration that the administration of macrophage activators can generate in situ tumoricidal activity in KC suggests that these cells can be important in the control of hepatic micrometastases. 相似文献
12.
P Anzenbacher J Hudecek S Vajda V Fidler C Larroque R Lange 《Biochemical and biophysical research communications》1991,181(3):1493-1499
Fluorescence of eight tryptophan residues in cytochrome P-450scc with bound endogenous cholesterol could be fitted with a two component model: a single exponential and a "top-hat" distribution of lifetimes as the second component. The short-lived component (tau 1 about 700 ps) does not change significantly upon binding of substrate (22R-hydroxycholesterol). The parameters of the long-lived component (central lifetime tau m about 3.4 ns) change upon binding of carbon monoxide and substrate. 22R-hydroxycholesterol binding broadens the distribution of the long-lived component; that is the heterogeneity of the Trp environment is increased when this substrate displaces the endogenous cholesterol. 相似文献
13.
The susceptibility of targets to destruction by tumoricidal rat and mouse macrophages was studied with virus-transformed cell lines in which various elements of the transformed phenotype are only expressed at specific temperatures. BHK cells transformed by the ts3 mutant of polyoma virus, rat embryo 3Y1 cells transformed by a temperature-sensitive A cistron mutant of simian virus 40 (SV40) and the ts-H6-15 temperature-sensitive line of SV40-transformed mouse 3T3 cells were killed in vitro by macrophages at both the permissive (33 °C) or nonpermissive (39 °C) temperatures for expression of the transformed phenotype. 3T3, 3Y1 and BHK cells transformed by wild-type SV40 or polyoma virus were also destroyed by tumoricidal macrophages at both 33 and 39 °C, but untransformed 3T3, 3Y1, and BHK cells were not. Thus, transformed cells are killed by macrophages regardless of whether or not they express cell surface LETS protein or Forssman antigen, display surface changes which permit agglutination by low doses of plant lectins, express SV40 T antigen, have a low saturation density, or exhibit density-dependent inhibition of DNA synthesis. 相似文献
14.
John M. Fidler 《Cellular immunology》1975,16(2):223-236
Lipopolysaccharide has been utilized as a carrier for the TNP hapten, producing an antigen which induces an in vivo thymus-independent antibody response to TNP as determined using athymic nude mice and their normal littermates. The immune response to TNP-LPS was investigated at both the antibody-forming cell and the serum antibody levels.The primary response to an optimal dose of TNP-LPS (1.0 μg) exhibited unusual kinetics reaching a sharp peak on day 3 of 58,000 anti-TNP PFC/spleen. Serum antibody to TNP was first detected on day 3 and reached a maximum log2 titer of 17.5 on day 5, an uncommonly high level for hapten-carrier conjugates and most carriers. Both the anti-TNP serum antibody and PFCs were exclusively IgM. No IgG antibody was detected in the primary response through 28 days postimmunization, nor was any detected in any experiment described in this paper. The primary PFC response to 1.0 μg of TNP-LPS was specific for TNP, producing no evidence of polyclonal antibody synthesis. The relative affinities of PFC-secreted antibody were investigated using hapten inhibition. The hapten inhibition curves for TNP-LPS and TNP-SRBC were very similar, indicating that relatively high affinity antibody was elicited by TNP-LPS. The secondary response to this dose following priming with TNP-SRBC or TNP-LPS was similar to the primary response, though the peak was less sharp in both cases. The response to the homologous secondary challenge shifted somewhat, reaching a peak on days 3–4. The effect of various doses in priming or challenging for the secondary response to TNP-LPS was investigated. Using an increased PFC response as a criterion, no dose was optimal for priming or immunological memory to TNP-LPS. While the adoptive primary response to TNP-LPS reached a low level peak on day 7, the adoptive secondary attained a maximum on day 6. This shift in kinetics in intact mice and in adoptive hosts in comparing primary to secondary responses indicated that a state of B cell priming may be induced. However, its full expression may be suppressed by endogenous factors at the time of priming, such as the high level of circulating anti-TNP antibody or residual antigen. Adoptive transfer would remove the cells from these influences, allowing such B cell priming to manifest itself fully. 相似文献
15.
A 30-gauge cannula was used to perfuse fixative through the fragile heart of a newborn opossum. The cannula was gently maneuvered into the heart and held in place with a specially designed manipulator. The flow rate of the fixative was regulated with an infusion set connected to the cannula. 相似文献
16.
Several statistical methods have been developed for adjusting the Odds Ratio of the relation between two dichotomous variables X and Y for some confounders Z. With the exception of the Mantel-Haenszel method, commonly used methods, notably binary logistic regression, are not symmetrical in X and Y. The classical Mantel-Haenszel method however only works for confounders with a limited number of discrete strata, which limits its utility, and appears to have no basis in statistical models. Here we revisit the Mantel-Haenszel method and propose an extension to continuous and vector valued Z. The idea is to replace the observed cell entries in strata of the Mantel-Haenszel procedure by subject specific classification probabilities for the four possible values of (X,Y) predicted by a suitable statistical model. For situations where X and Y can be treated symmetrically we propose and explore the multinomial logistic model. Under the homogeneity hypothesis, which states that the odds ratio does not depend on Z, the logarithm of the odds ratio estimator can be expressed as a simple linear combination of three parameters of this model. Methods for testing the homogeneity hypothesis are proposed. The relationship between this method and binary logistic regression is explored. A numerical example using survey data is presented. 相似文献
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19.
Fidler AE Gwinner E 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2003,136(4):861-874
Animals differ widely in the phasing of their daily rhythms with respect to daily environmental rhythms. While birds are predominantly day-active, nocturnal activity is a characteristic feature of the order Strigiformes (owls). To study the evolution of owl night-activity cDNA sequences encoding the circadian core oscillator (CCO) proteins BMAL1 and CLOCK were obtained from barn owl (Tyto alba). The predicted proteins showed high sequence identity with their Galliform homologues (BMAL1: 99%; CLOCK: 95.6%). A computer-predicted chicken BMAL1 casein kinase-1 phosphorylation site is absent from T. alba BMAL1, but also absent from homologues of other six bird species (5 orders) (night-active (n=2), day-active (n=4)) indicating no evolutionary association with night activity. Sequence differences between T. alba and Galliform CLOCK frequently involved serine and threonine residues suggesting potential differences in their phosphorylation. The length of a poly-glutamine string in the CLOCK C-terminus varied between and within 25 species (6 orders) examined, however, no discernible feature distinguishing day and night active species was found. No differences were found between day (n=5) and night (n=7)-active species (12 species, 6 orders) in a region of the PER2 protein implicated in altered rhythm phasing in humans. In conclusion the avian CCO components examined showed strong evolutionary conservation. Molecular evolution associated with owl night-activity may have involved alterations in the CCO relationship with ‘output’ genes rather than in the molecular structure of the CCO itself. 相似文献
20.
Shinohara H Yano S Bucana CD Fidler IJ 《Journal of immunology (Baltimore, Md. : 1950)》2000,164(5):2728-2737
We investigated the role of tumor cell-derived GM-CSF in recruitment and tumoricidal activation of tissue macrophages. Transfection of the murine GM-CSF gene into KM12SM human colon cancer cells decreased the tumorigenicity of transfected cells and nontransfected bystander colon cancer cells in nude mice. Sequential tissue sections from sites injected with high GM-CSF-producing tumor cells (but not from nontransfected or low GM-CSF-producing cells) demonstrated a dense infiltration of polymorphonuclear cells (PMN), followed by infiltration of macrophages, which correlated with expression of the macrophage-inflammatory protein-1alpha and the monocyte chemoattractant protein-1 (MCP-1) in mouse PMN and macrophages. GM-CSF-producing KM12SM cells were highly sensitive to lysis by mouse macrophages and also increased macrophage-mediated lysis of bystander nontransfected KM12SM cells. The incubation of macrophages with GM-CSF induced expression of the CD11b surface adhesion molecule, which was associated with increased attachment to tumor cells. All KM12SM cells were sensitive to macrophage-mediated lysis in the presence of rGM-CSF and recombinant MCP-1. Collectively, the results demonstrate that tumor cell-derived GM-CSF stimulates PMN and macrophages to secrete macrophage-inflammatory protein-1alpha and MCP-1, which triggers recruitment of mononuclear cells, induces expression of adhesion molecules on macrophages, and enhances contact-dependent cytolysis of tumor cells. 相似文献