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631.
Stimulus-secretion coupling in exocrine glands involves Ca2+ release from intracellular stores. In endoplasmic reticulum vesicle preparations from rat exocrine pancreas, an inositol 1,4,5-trisphosphate(InsP3)-sensitive, as well as an InsP3-insensitive, Ca2+ pool has been characterized. But Ca2+ channels in the endoplasmic reticulum of rat exocrine pancreas have not been demonstrated at the level of single-channel current. We have now used the patch-clamp technique on endoplasmic reticulum vesicles fused by means of the dehydration-rehydration method. In excised patches, single Ba2(+)- and Ca2(+)-selective channels were recorded. The channel activity was markedly voltage-dependent. Caffeine increased channel open-state probability, whereas ruthenium red and Cd2+ blocked single-channel currents. Ryanodine, nifedipine and heparin had no effect on channel activity. The channel activity was not dependent on the free Ca2+ concentration, the presence of InsP3, or pH. We conclude that this calcium channel mediates Ca2+ release from an intracellular store through an InsP3-insensitive mechanism.  相似文献   
632.
D Ingber  T Fujita  S Kishimoto  K Sudo  T Kanamaru  H Brem  J Folkman 《Nature》1990,348(6301):555-557
Neovascularization is critical for the growth of tumours and is a dominant feature in a variety of angiogenic diseases such as diabetic retinopathy, haemangiomas, arthritis and psoriasis. Recognition of the potential therapeutic benefit of controlling unabated capillary growth has led to a search for safe and effective angiogenesis inhibitors. We report here the synthesis of a family of novel inhibitors that are analogues of fumagillin, a naturally secreted antibiotic of Aspergillus fumigatus fresenius. We first isolated this fungus from a contaminated culture of capillary endothelial cells. Purified fumagillin inhibited endothelial cell proliferation in vitro and tumour-induced angiogenesis in vivo; it also inhibited tumour growth in mice, but prolonged administration was limited because it caused severe weight loss. Synthesis of fumagillin analogues yielded potent angiogenesis inhibitors ('angioinhibins') which suppress the growth of a wide variety of tumours with relatively few side-effects.  相似文献   
633.
634.
Mammalian sex chromosomes share a small terminal region of homologous DNA sequences, which pair and recombine during male meiosis. Alleles in this region can be exchanged between X and Y chromosomes and are therefore inherited as if autosomal. Genes from this so-called pseudoautosomal region (PAR) are present in two doses in both males and females, and escape inactivation of the X chromosome in females. Indirect evidence suggests that there must be several pseudoautosomal genes, and several candidates have been proposed. Until now, the only gene that has been unequivocally located in the PAR is MIC2, which encodes a cell-surface antigen of unknown function. We now report the localization of a gene of known function to this region--the gene for the receptor of the haemopoietic regulator, granulocyte-macrophage colony stimulating factor. The chromosomal localization of this gene may be important in understanding the generation of M2 acute myeloid leukaemia.  相似文献   
635.
T Sakurai  M Yanagisawa  Y Takuwa  H Miyazaki  S Kimura  K Goto  T Masaki 《Nature》1990,348(6303):732-735
Endothelin-1 was initially identified as a 21-residue potent vasoconstrictor peptide produced by vascular endothelial cells, but was subsequently found to have many effects on both vascular and non-vascular tissues. The discovery of three isopeptides of the endothelin family, ET-1, ET-2 and ET-3, each possessing a diverse set of pharmacological activities of different potency, suggested the existence of several different endothelin receptor subtypes. Endothelins may elicit biological responses by various signal-transduction mechanisms, including the G protein-coupled activation of phospholipase C and the activation of voltage-dependent Ca2+ channels. Thus, different subtypes of the endothelin receptor may use different signal-transduction mechanisms. Here we report the cloning of a complementary DNA encoding one subtype belonging to the superfamily of G protein-coupled receptors. COS-7 cells transfected with the cDNA express specific and high-affinity binding sites for endothelins, responding to binding by the production of inositol phosphates and a transient increase in the concentration of intracellular free Ca2+. The three endothelin isopeptides are roughly equipotent in displacing 125I-labelled ET-1 binding and causing Ca2+ mobilization. A messenger RNA corresponding to the cDNA is detected in many rat tissues including the brain, kidney and lung but not in vascular smooth muscle cells. These results indicate that this cDNA encodes a 'nonselective' subtype of the receptor which is different from the vascular smooth muscle receptor.  相似文献   
636.
探讨了溅射用铁电陶瓷靶(PZT,PLZT)的烧结工艺,并对其显微结构进行了分析。结果表明,采用新的烧结工艺(含保护措施),可以有效地抑制PbO的挥发,制备出组织结构及成分均匀、PbO含量正常、致密度较高、不变形的符合磁控溅射要求的铁电陶瓷烧结靶。  相似文献   
637.
基于对时间序列实质的分析,提出了旨在减少序列的随机误差影响以及提高拟合精度的AR模型参数的积分求解法.重点讨论了AR(1)模型及AR(p)模型参数的积分求解法,并与最小二乘法在计算机上进行了仿真比较.结果表明,采用积分求解法所得的AR模型参数的估计精度比最小二乘法的高.  相似文献   
638.
强反射层追踪与相对时差拾取中的“多值”现象严重影响剩余静校正的效果,为此提出的小波包预处理方法,可以实现地震道噪声与信号及不同强反射层的分离,从而能自动识别并提取“纯”的强反射层,提高强反射层追踪的可靠性和相对时差的拾取精度.  相似文献   
639.
对几种逆变电源的抗冲击性负荷电路进行分析,给出了一种便于实现且效果很好的电路,实验证明此电路对各种冲击负荷甚至输出短路都能进行很好的限流,可以彻底解决逆变电源在负载冲击下频繁停机的问题。  相似文献   
640.
利用Gurson本构理论,导出了损伤材料在平面应力条件下准静态定常扩展I型裂纹近裂纹线应力场和裂纹前方塑性区尺寸的解析表达式。研究结果表明:随着材料损伤量的增加,裂纹尖端处应力降低;裂纹尖端处应力不存在奇异性;裂纹前方塑性区尺寸受材料损伤程度的影响。  相似文献   
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