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91.
An antiserum was raised in rabbits against a primary metastasizing lymphosarcoma (ML) of the hamster. This was made tumor-specific by absorption with normal hamster tissue extracts. Immunoglobulin-G was prepared and tested for its cytotoxicity towards cells derived from the primary tumor and its liver metastases. The ML-specific IgG was found to be 2--5 times more cytotoxic for cells derived from the primary tumor compared to cells obtained from liver metastases. 相似文献
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Mortality forecasting is important for life insurance policies, as well as in other areas. Current techniques for forecasting mortality in the USA involve the use of the Lee–Carter model, which is primarily used without regard to cause. A method for forecasting morality is proposed which involves the use of neural networks. A comparative analysis is done between the Lee–Carter model, linear trend and the proposed method. The results confirm that the use of neural networks performs better than the Lee–Carter and linear trend model within 5% error. Furthermore, mortality rates and life expectancy were formulated for individuals with a specific cause based on prevalence data. The rates are broken down further into respective stages (cancer) based on the individual's diagnosis. Therefore, this approach allows life expectancy to be calculated based on an individual's state of health. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
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The clinical success of the ABL tyrosine kinase inhibitor imatinib in chronic myeloid leukaemia (CML) serves as a model for molecularly targeted therapy of cancer, but at least two critical questions remain. Can imatinib eradicate leukaemic stem cells? What are the dynamics of relapse due to imatinib resistance, which is caused by mutations in the ABL kinase domain? The precise understanding of how imatinib exerts its therapeutic effect in CML and the ability to measure disease burden by quantitative polymerase chain reaction provide an opportunity to develop a mathematical approach. We find that a four-compartment model, based on the known biology of haematopoietic differentiation, can explain the kinetics of the molecular response to imatinib in a 169-patient data set. Successful therapy leads to a biphasic exponential decline of leukaemic cells. The first slope of 0.05 per day represents the turnover rate of differentiated leukaemic cells, while the second slope of 0.008 per day represents the turnover rate of leukaemic progenitors. The model suggests that imatinib is a potent inhibitor of the production of differentiated leukaemic cells, but does not deplete leukaemic stem cells. We calculate the probability of developing imatinib resistance mutations and estimate the time until detection of resistance. Our model provides the first quantitative insights into the in vivo kinetics of a human cancer. 相似文献
96.
采用复型技术,在透射电镜中观察到厚度大于0.5μm的蒸发淀积Al膜的显微结构,实验结果表明,膜的表面呈岛状结构,侧面呈柱状结构,同时也探讨了影响“柱”直径大小的因素。 相似文献
97.
Bacterial chromosomes often carry integrated genetic elements (for example plasmids, transposons, prophages and islands) whose precise function and contribution to the evolutionary fitness of the host bacterium are unknown. The CTXφ prophage, which encodes cholera toxin in Vibrio cholerae, is known to be adjacent to a chromosomally integrated element of unknown function termed the toxin-linked cryptic (TLC). Here we report the characterization of a TLC-related element that corresponds to the genome of a satellite filamentous phage (TLC-Knφ1), which uses the morphogenesis genes of another filamentous phage (fs2φ) to form infectious TLC-Knφ1 phage particles. The TLC-Knφ1 phage genome carries a sequence similar to the dif recombination sequence, which functions in chromosome dimer resolution using XerC and XerD recombinases. The dif sequence is also exploited by lysogenic filamentous phages (for example CTXφ) for chromosomal integration of their genomes. Bacterial cells defective in the dimer resolution often show an aberrant filamentous cell morphology. We found that acquisition and chromosomal integration of the TLC-Knφ1 genome restored a perfect dif site and normal morphology to V.?cholerae wild-type and mutant strains with dif(-) filamentation phenotypes. Furthermore, lysogeny of a dif(-) non-toxigenic V.?cholerae with TLC-Knφ1 promoted its subsequent toxigenic conversion through integration of CTXφ into the restored dif site. These results reveal a remarkable level of cooperative interactions between multiple filamentous phages in the emergence of the bacterial pathogen that causes cholera. 相似文献
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Sanna S Jackson AU Nagaraja R Willer CJ Chen WM Bonnycastle LL Shen H Timpson N Lettre G Usala G Chines PS Stringham HM Scott LJ Dei M Lai S Albai G Crisponi L Naitza S Doheny KF Pugh EW Ben-Shlomo Y Ebrahim S Lawlor DA Bergman RN Watanabe RM Uda M Tuomilehto J Coresh J Hirschhorn JN Shuldiner AR Schlessinger D Collins FS Davey Smith G Boerwinkle E Cao A Boehnke M Abecasis GR Mohlke KL 《Nature genetics》2008,40(2):198-203
100.
THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia 总被引:1,自引:0,他引:1
Tran PV Haycraft CJ Besschetnova TY Turbe-Doan A Stottmann RW Herron BJ Chesebro AL Qiu H Scherz PJ Shah JV Yoder BK Beier DR 《Nature genetics》2008,40(4):403-410
Characterization of previously described intraflagellar transport (IFT) mouse mutants has led to the proposition that normal primary cilia are required for mammalian cells to respond to the sonic hedgehog (SHH) signal. Here we describe an N-ethyl-N-nitrosourea-induced mutant mouse, alien (aln), which has abnormal primary cilia and shows overactivation of the SHH pathway. The aln locus encodes a novel protein, THM1 (tetratricopeptide repeat-containing hedgehog modulator-1), which localizes to cilia. aln-mutant cilia have bulb-like structures at their tips in which IFT proteins (such as IFT88) are sequestered, characteristic of Chlamydomonas reinhardtii and Caenorhabditis elegans retrograde IFT mutants. RNA-interference knockdown of Ttc21b (which we call Thm1 and which encodes THM1) in mouse inner medullary collecting duct cells expressing an IFT88-enhanced yellow fluorescent protein fusion recapitulated the aln-mutant cilial phenotype, and live imaging of these cells revealed impaired retrograde IFT. In contrast to previously described IFT mutants, Smoothened and full-length glioblastoma (GLI) proteins localize to aln-mutant cilia. We hypothesize that the aln retrograde IFT defect causes sequestration of IFT proteins in aln-mutant cilia and leads to the overactivated SHH signaling phenotype. Specifically, the aln mutation uncouples the roles of anterograde and retrograde transport in SHH signaling, suggesting that anterograde IFT is required for GLI activation and that retrograde IFT modulates this event. 相似文献