Effect of spermine on adenyl cyclase activity of spermatozoa

Zusammenfassung Zusätze physiologischer Sperminkonzentrationen (2–14 mM) zu menschlichen Spermiensuspensionen bewirken eine Steigerung der Adenylcyclase-Aktivität, wie sie durch die vermehrte Bildung von cAMP aus ATP angezeigt wird.     

Dynamics of chronic myeloid leukaemia

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.     

Comparison of DMSO and glycerol as cryoprotectants for ascites tumor cells

Summary Mouse Ehrlich ascites and rat D23 ascites tumors were stored in liquid nitrogen under identical conditions for up to 3 years. Cell viability (trypan blue exclusion) and transplantability of both tumors in animals remained virtually unaffected if preserved in 10% DMSO containing medium, whereas, cells preserved in 10% glycerol failed to produce lethal tumors in rodents.This work was performed at the Cancer Research Unit, Royal Victoria Infirmary, Newcastle Upon Tyne, England. I thank John Geggie for expert technical assistance; to the North of England Council of the Cancer Research Campaign and the National Science Foundation (ENG-78-25432) for financial support; and to Dr John A. Dickson for advice and encouragement. Also, I am indebted to Professor Rakesh K. Jain for his support.     

Antigenic differences between a primary hamster lymphosarcoma and its liver metastases

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.     

Satellite phage TLCφ enables toxigenic conversion by CTX phage through dif site alteration

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.     

考虑震损的混凝土框架结构改进建模方法

为准确描述震后结构损伤的影响,提出了损伤构件的定量分析方法及震损结构的改进建模方法.首先,从骨架曲线退化及滞回规则退化两方面定义了损伤构件的性能退化指数;然后,基于Park-Ang模型与Kunnath模型,采用统计回归分析方法提出了损伤构件恢复力模型,并对其准确性进行了验证;最后,应用该恢复力模型对震损框架结构进行弹塑性分析.结果 表明:采用Park-Ang模型和Kunnath模型得到的损伤构件恢复力模型均具有较高的准确性;对于所研究的2种构件,滞回曲线力峰值的理论值和试验值误差均小于10％;向完好结构输入组合地震波,向震损结构输入单一地震波,各层位移时程曲线吻合良好,说明采用该恢复力模型进行震损结构建模能够准确分析震损程度及分布对结构抗震性能的影响.