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81.
82.
Our knowledge in immunology has been dramatically increased by several excellent investigations elucidating the role of the Fas (Apo-1/CD95) receptor/ligand (FasL) system in complex immunological processes such as the acquisition of self tolerance in T cells, progression of autoimmunity, clonal deletion of activated T cells, B-cell regulation and the establishment of "immune privileged" sites such as testis or retina. In addition to these regulatory immunological activities, Fas/FasL interaction was also shown to participate in active defense mechanisms of the host against infected or transformed cells thereby inducing apoptosis in target cells. However, the same mechanism seems also to be part of an escape strategy utilized by tumor cells in various neoplastic malignancies of both hematopoetic as also non-hematopoetic origin. We ourselves were able to demonstrate that neoplastic plasma cell lines, as well as native malignant myeloma cells constitutively express FasL mRNA and protein. The FasL molecule is functionally active and able to induce programmed cell death in Fas sensitive target T cells in vitro. These target T cells were protected from programmed cell death by preincubation of T cells with a Fas-blocking monoclonal antibody (mAb) or of myeloma cells with a FasL-neutralizing mAb. respectively. Furthermore, overexpression of the caspase inhibitor, cowpoxvirus protein CrmA, also protected target T cells from being killed by myeloma cells, identifying Fas/FasL mediated signaling as the effector pathway utilized by malignant plasma cells. Our observations strongly suggest the engagement of Fas/FasL interaction in the escape strategy of this malignancy. The molecular basis of this evasive mechanism differs in essential respects from those described in melanoma, lung cancer, hepatocellular carcinoma, or astrocytoma, since downregulation of Fas or instrinsic insensitivity towards Fas-mediated signaling were not prerequisites for the occurrence of this phenomenon in Fas-sensitive multiple myeloma cell lines. However, myeloma cell lines resisted cocultivation with FasL-expressing target T cells in vitro. The aim of this review is to discuss the role of Fas/FasL interaction in the establishment of malignant disease, in the light of our findings on myeloma cells and also by drawing upon similar observations of other investigators on different kinds of tumor cells and cell lines and further to consider its possible relevance in formulating novel approaches to cancer therapy. 相似文献
83.
Juvenile Eisenia fetida (Savigny) were exposed for 20 weeks to an uncontaminated soil and to soils contaminated with cadmium, copper, lead, and zinc collected from seven sites at different distances from a smelting works at Avonmouth, southwest England. The survival, growth (= weight after 5 weeks exposure), time to sexual maturation (= percentages of adults present after 8 weeks), and reproduction (= number of cocoons produced by the worms) were compared with soil metal concentrations. Of the parameters measured, growth and sexual maturation time had the lowest EC50 values. The effects of metal-contaminated soils could be attributed both to the direct toxicity of the metals and to changes in the "scope for growth" of the exposed worms. A comparison of the results with those of an earlier toxicity test conducted with adult worms indicated that juveniles are more sensitive to metals than adults. Significant toxic effects on the growth and sexual maturation times of juveniles were detected in soils from sites for which no significant effects on the cocoon production of adults could be detected. The greater sensitivity of juvenile worms indicates the importance of considering effects on a variety of life history stages when conducting a risk assessment of the effects of pollutants in soils. Although E. fetida does not occur naturally in soils at Avonmouth, the present study provides evidence to support the suggestion that pollution from the smelter is responsible for the absence of worms within 2 km of the factory. Results presented in this paper, and from previous studies, suggest the observed absence is due to the effects of zinc on the growth and maturation of juveniles and the cocoon production rate of adult worms. 相似文献
84.
The objective of the research described was to devise an efficient procedure to cryopreserve in vitro-matured bovine oocytes, using in vitro fertilization (IVF) and development of resultant zygotes into blastocysts as criteria of oocyte survival. Oocytes at metaphase II were found to be extremely sensitive to chilling. Cooling them to O degrees C for as little as 5 sec significantly decreased their capability to cleave and develop further after IVF; after 80 sec at 0 degrees C, only approximately 10% of chilled oocytes developed into blastocysts. Oocytes were also adversely affected by brief exposures to 4 M and 5.5 M ethylene glycol (EG) solutions supplemented with sucrose; after being suspended in either of these EG solutions in plastic straws and plunged directly into liquid nitrogen (LN2), few of the oocytes were fertilized and developed. To "outrace" chilling injury, oocytes contained in < 1 microliter of EG solution were placed onto electron microscope grids and plunged directly into N2 slush or LN2. After such ultra-rapidly cooled oocytes were warmed, 30% of them cleaved after IVF, and half of these developed into blastocysts-- survival rates equivalent to those for oocytes that had been exposed to EG without any cooling. This method offers promise as a novel way to cryopreserve bovine oocytes. 相似文献
85.
JD Reveille GS Alarcón SE Fowler SR Pillemer R Neuner DO Clegg IS Mikhail DE Trentham JC Leisen G Bluhm SM Cooper H Duncan M Tuttleman SP Heyse JT Sharp B Tilley 《Canadian Metallurgical Quarterly》1996,39(11):1802-1807
OBJECTIVE: To examine the effect of alleles encoding the "shared"/"rheumatoid" epitope on rheumatoid arthritis (RA) disease severity in patients who participated in the minocycline in RA (MIRA) trial. METHODS: Of 205 patients with a week-48 visit, blood was available for typing of HLA-DRB1 and HLA-DQB1 in 174 (85%) and successfully completed in 169 (82%). Baseline erosions were used to assess disease severity and new erosions at the last visit served as a proxy for progression. RESULTS: At baseline, there was no association between the presence of erosive disease or rheumatoid factor status and the dose of rheumatoid epitope (homozygous, heterozygous, none) or the specific alleles identified. At the final visit, a gradient was observed for the 3 allelic subgroups (and their gene doses) in the occurrence of new erosions among the Caucasian placebo-treated, but not the minocycline-treated, patients. A treatment group/HLA-DR4 epitope interaction was demonstrated in multivariate analyses. Approximately two-thirds of African-American patients did not have the rheumatoid epitope. CONCLUSION: HLA-DRB1 oligotyping may be useful in predicting the progression of disease in some Caucasian patients. Our study corroborates the infrequency of the epitope among African-American patients with RA. 相似文献
86.
Hans De Sterck Killian Miller Geoffrey Sanders 《Computing and Visualization in Science》2011,14(2):51-65
Recently, it was shown how the convergence of a class of multigrid methods for computing the stationary distribution of sparse,
irreducible Markov chains can be accelerated by the addition of an outer iteration based on iterant recombination. The acceleration
was performed by selecting a linear combination of previous fine-level iterates with probability constraints to minimize the
two-norm of the residual using a quadratic programming method. In this paper we investigate the alternative of minimizing
the one-norm of the residual. This gives rise to a nonlinear convex program which must be solved at each acceleration step.
To solve this minimization problem we propose to use a deep-cuts ellipsoid method for nonlinear convex programs. The main
purpose of this paper is to investigate whether an iterant recombination approach can be obtained in this way that is competitive
in terms of execution time and robustness. We derive formulas for subgradients of the one-norm objective function and the
constraint functions, and show how an initial ellipsoid can be constructed that is guaranteed to contain the exact solution
and give conditions for its existence. We also investigate using the ellipsoid method to minimize the two-norm. Numerical
tests show that the one-norm and two-norm acceleration procedures yield a similar reduction in the number of multigrid cycles.
The tests also indicate that one-norm ellipsoid acceleration is competitive with two-norm quadratic programming acceleration
in terms of running time with improved robustness. 相似文献
87.
88.
An empirical model of a liquid crystalline (L alpha phase) phosphatidylcholine (PC) bilayer interface is presented along with a function which calculates the position-dependent energy of associated solutes. The model approximates the interface as a gradual two-step transition, the first step being from an aqueous phase to a phase of reduced polarity, but which maintains a high enough concentration of water and/or polar head group moieties to satisfy the hydrogen bond-forming potential of the solute. The second transition is from the hydrogen bonding/low polarity region to an effectively anhydrous hydrocarbon phase. The "interfacial energies" of solutes within this variable medium are calculated based upon atomic positions and atomic parameters describing general polarity and hydrogen bond donor/acceptor propensities. This function was tested for its ability to reproduce experimental water-solvent partitioning energies and water-bilayer partitioning data. In both cases, the experimental data was reproduced fairly well. Energy minimizations carried out on beta-hexyl glucopyranoside led to identification of a global minimum for the interface-associated glycolipid which exhibited glycosidic torsion angles in agreement with prior results (Hare, B.J., K.P. Howard, and J.H. Prestegard. 1993. Biophys. J. 64:392-398). Molecular dynamics simulations carried out upon this same molecule within the simulated interface led to results which were consistent with a number of experimentally based conclusions from previous work, but failed to quantitatively reproduce an available NMR quadrupolar/dipolar coupling data set (Sanders, C.R., and J.H. Prestegard. 1991. J. Am. Chem. Soc. 113:1987-1996). The proposed model and functions are readily incorporated into computational energy modeling algorithms and may prove useful in future studies of membrane-associated molecules. 相似文献
89.
90.