Does the release of potassium from astrocyte endfeet regulate cerebral blood flow?

Local increases in neuronal activity within the brain lead to dilation of blood vessels and to increased regional cerebral blood flow. Increases in extracellular potassium concentration are known to dilate cerebral arterioles. Recent studies have suggested that the potassium released by active neurons is transported through astrocytic glial cells and released from their endfeet onto blood vessels. The results of computer simulations of potassium dynamics in the brain indicate that the release of potassium from astrocyte endfeet raises perivascular potassium concentration much more rapidly and to higher levels than does diffusion of potassium through extracellular space, particularly when the site of a potassium increase is some distance from the vessel wall. On the basis of this finding, it is proposed that the release of potassium from astrocyte endfeet plays an important role in regulating regional cerebral blood flow in response to changes in neuronal activity.     

水通道蛋白在小鼠嗅上皮中的免疫定位

采用免疫印迹和免疫组织化学技术分析水通道蛋白(Aquaporins,AQPs)在小鼠嗅上皮细胞中的表达情况。结果表明:AQP1在血管内皮细胞表达,AQP3在下层支持细胞和基底细胞表达,AQP4在上层支持细胞和基底细胞表达;AQP5在嗅毛和鲍曼氏腺的分泌细胞和导管细胞表达。结果显示了水通道蛋白在小鼠嗅上皮细胞中的表达位置,其中在支持细胞和基底细胞表达的AQP3和AQP4可能为嗅神经功能的维持提供了重要的微环境,在嗅毛和鲍曼氏腺的分泌细胞和导管细胞表达的AQP5可能在气味的感受方面起作用。     

壶瓶枣果实发育过程中果柄导管形态变化与裂果关系

【目的】阐明壶瓶枣果实发育过程中果柄导管形态及运输效率的变化,明确果实通过维管束系统吸水与其裂果的关系,完善枣裂果机理。【方法】以壶瓶枣（Ziziphus jujube Mill. cv. Huping）为试材,于白熟期（8月19日）开始对选定枣树进行定量灌溉处理,每7 d测定、灌溉一次,使处理组土壤含水量维持在田间最大持水量的（80±5）%,对照组的土壤含水量控制在田间最大持水量的（20±5）%。于果实发育后期分别调查降雨前（9月18日）、降雨后（9月22日）枣果的裂果率;分别在幼果期（7月28日）、白熟期（8月15日）、半红期（9月5日）和全红期（9月17日）进行采样,跟踪枣果实发育进程。品红示踪试验中采用二次枝浸泡和枣吊浸泡两种形式,观察不同时期二次枝、枣吊和果柄维管束系统运输效率的变化;取健康枣果的果柄进行石蜡切片,经FAA液固定、常规方法包埋、制作切片、番红-固绿复染,观察枣果果柄导管形态随果实发育的变化规律。【结果】裂果率调查结果显示,枣果发育后期灌溉和对照两种处理的裂果率分别为2.60%和2.58%,二者间差异不显著,表明充足灌溉并未引起裂果;降雨后,灌溉组和对照组处理的裂果率与降雨前相比均显著升高,分别达到42.90%和40.80%,且两组间差异并不显著,表明降雨会明显导致裂果率上升。品红示踪试验结果表明,在整个果实发育期,品红溶液均能通过二次枝顺畅运送至枣吊,但能否运送至枣果与果实发育期密切相关。幼果期,品红溶液在5 min之内便可顺利输送至枣果,且输送数量和范围随着时间延长而逐渐增大;随着果实发育,品红运输至枣果的难度逐渐增大,白熟期时处理40 min后仅有少许品红输送至枣果;至半红期和全红期,品红溶液几乎不能输送至枣果,这表明果柄可能是品红不能顺利运输至枣果的主要障碍。石蜡切片结果表明,幼果期正常导管所占比例为97.22%,白熟期时正常导管的比例下降至34.95%,且开始出现断裂、退化和畸形,半红期和全红期正常导管的比例仅剩13%左右,导管断裂、退化和畸形进一步加剧,并且开始出现导管堵塞现象,且全红期导管堵塞的数量和程度均高于半红期。【结论】壶瓶枣果实发育后期,果柄导管出现断裂、畸形、退化、堵塞等现象,其运输能力受损或丧失,导致根系吸收的水分难以通过“根系-枝干-二次枝-枣吊-果柄-果实”维管束系统大量进入果实,从而不会引发大量裂果。     

A role for thrombin receptor signaling in endothelial cells during embryonic development

The coagulation protease thrombin triggers fibrin formation, platelet activation, and other cellular responses at sites of tissue injury. We report a role for PAR1, a protease-activated G protein-coupled receptor for thrombin, in embryonic development. Approximately half of Par1-/- mouse embryos died at midgestation with bleeding from multiple sites. PAR1 is expressed in endothelial cells, and a PAR1 transgene driven by an endothelial-specific promoter prevented death of Par1-/- embryos. Our results suggest that the coagulation cascade and PAR1 modulate endothelial cell function in developing blood vessels and that thrombin's actions on endothelial cells-rather than on platelets, mesenchymal cells, or fibrinogen-contribute to vascular development and hemostasis in the mouse embryo.     

Tissue factor (thromboplastin): localization to plasma membranes by peroxidase-conjugated antibodies

Peroxidase-conjugated antibodies were used to determine the histologic and cytologic localization of bovine and human tissue factor (thromboplastin). Tissue factor antigen was found in highest concentration in the intima of blood vessels, particularly in the plasma membranes of endothelial cells and in human atheromatous plaques. Tissue factor was also found limited to the plasma membranes of many cell types. The presence of tissue factor in the plasma membranes of endothelial cells and atheromata suggests that it may play a significant role in hemostasis and thrombosis.     

Liver organogenesis promoted by endothelial cells prior to vascular function

The embryonic role of endothelial cells and nascent vessels in promoting organogenesis, prior to vascular function, is unclear. We find that early endothelial cells in mouse embryos surround newly specified hepatic endoderm and delimit the mesenchymal domain into which the liver bud grows. In flk-1 mutant embryos, which lack endothelial cells, hepatic specification occurs, but liver morphogenesis fails prior to mesenchyme invasion. We developed an embryo tissue explant system that permits liver bud vasculogenesis and show that in the absence of endothelial cells, or when the latter are inhibited, there is a selective defect in hepatic outgrowth. We conclude that vasculogenic endothelial cells and nascent vessels are critical for the earliest stages of organogenesis, prior to blood vessel function.     

新生儿Fc受体的研究进展

新生儿Fc受体(FcRn)是负责上皮细胞主动转运免疫球蛋白IgG的受体.IgG是初乳中含量最丰富的免疫球蛋白成分,哺乳动物新生儿的免疫力主要依赖于从母体获得IgG,而母源IgG向乳汁中的分泌以及被新生儿摄取均需要穿越上皮屏障,这一过程就是FcRn的胞转作用.本文对FcRn的特性、转运机制及其研究进展进行综述.     

Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk

Lymphatic vessels develop from specialized endothelial cells in preexisting blood vessels, but the molecular signals that regulate this separation are unknown. Here we identify a failure to separate emerging lymphatic vessels from blood vessels in mice lacking the hematopoietic signaling protein SLP-76 or Syk. Blood-lymphatic connections lead to embryonic hemorrhage and arteriovenous shunting. Expression of slp-76 could not be detected in endothelial cells, and blood-filled lymphatics also arose in wild-type mice reconstituted with SLP-76-deficient bone marrow. These studies reveal a hematopoietic signaling pathway required for separation of the two major vascular networks in mammals.     

Tumor regression by targeted gene delivery to the neovasculature

Efforts to influence the biology of blood vessels by gene delivery have been hampered by a lack of targeting vectors specific for endothelial cells in diseased tissues. Here we show that a cationic nanoparticle (NP) coupled to an integrin alphavbeta3-targeting ligand can deliver genes selectively to angiogenic blood vessels in tumor-bearing mice. The therapeutic efficacy of this approach was tested by generating NPs conjugated to a mutant Raf gene, ATPmu-Raf, which blocks endothelial signaling and angiogenesis in response to multiple growth factors. Systemic injection of the NP into mice resulted in apoptosis of the tumor-associated endothelium, ultimately leading to tumor cell apoptosis and sustained regression of established primary and metastatic tumors.     

Insulin receptor phosphorylation may not be a prerequisite for acute insulin action

An antiserum to the insulin receptor mimicked insulin's acute actions on glucose transport, phosphorylation of integral membrane proteins, and internalization of the insulin receptor in isolated rat adipose cells. These insulinomimetic actions of the antiserum occurred without the equivalent increase in phosphorylation of the beta subunit of the insulin receptor observed with insulin. Thus, a role of receptor phosphorylation in acute insulin action is now questioned.     

Defect in phosphorylation of insulin receptors in cells from an insulin-resistant patient with normal insulin binding

Mononuclear blood cells were obtained from a patient with type A insulin resistance. The cells showed a normal ability to bind iodine 125-labeled insulin. Analysis of solubilized insulin receptors from the patient's cells revealed a defect in insulin-stimulated tyrosine kinase activity, which is closely associated with the receptor itself. The enzyme failed to phosphorylate the insulin receptor and showed a markedly reduced ability to phosphorylate exogenously added substrates. It appears that receptors from this insulin-resistant patient have a defect distal to the insulin-binding site (the alpha subunit of the receptor). The defect could be located in the beta subunit, which has an adenosine triphosphate-binding site, or in another receptor component that transfers a signal of insulin binding into kinase activity. This dissociation between the normal binding and the defective protein kinase component of the insulin receptor represents the first biochemical defect of the receptor distal to ligand binding.     

Phenylalanine: Transplacental centrations in Rhesus Monkeys

Arbino acids are actively transported across the mammalian placenta, crncentrations in fetal blood being higher than those in the maternal circu-Elevated concentrations of phenylalanine were induced by dietarv means blood of pregnant rhesus monkeys, and the active transport mechanism vident at both normal and elevated concentrations. A normal placental may thus magnify a maternal biochemical abnormality and produce a profound disturbance in the fetus.     

Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins

The development of a patterned vasculature is essential for normal organogenesis. We found that signaling by semaphorin 3E (Sema3E) and its receptor plexin-D1 controls endothelial cell positioning and the patterning of the developing vasculature in the mouse. Sema3E is highly expressed in developing somites, where it acts as a repulsive cue for plexin-D1-expressing endothelial cells of adjacent intersomitic vessels. Sema3E-plexin-D1 signaling did not require neuropilins, which were previously presumed to be obligate Sema3 coreceptors. Moreover, genetic ablation of Sema3E or plexin-D1 but not neuropilin-mediated Sema3 signaling disrupted vascular patterning. These findings reveal an unexpected semaphorin signaling pathway and define a mechanism for controlling vascular patterning.     

Heparan sulfate degradation: relation to tumor invasive and metastatic properties of mouse B16 melanoma sublines

After transport in the blood and implantation in the microcirculation, metastatic tumor cells must invade the vascular endothelium and underlying basal lamina. Mouse B16 melanoma sublines were used to determine the relation between metastatic properties and the ability of the sublines to degrade enzymatically the sulfated glycosaminoglycans present in the extracellular matrix of cultured vascular endothelial cells. Highly invasive and metastatic B16 sublines degraded matrix glycosaminoglycans faster than did sublines of lower metastatic potential. The main products of this matrix degradation were heparan sulfate fragments. Intact B16 cells (or their cell-free homogenates) with a high potential for lung colonization degraded purified heparan sulfate from bovine lung at higher rates than did B16 cells with a poor potential for lung colonization. Analysis of the degradation fragments indicated that B16 cells have a heparan sulfate endoglycosidase. Thus the abilities of B16 melanoma cells to extravasate and successfully colonize the lung may be related to their capacities to degrade heparan sulfate in the walls of pulmonary blood vessels.     

Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene

Protein tyrosine phosphatase-1B (PTP-1B) has been implicated in the negative regulation of insulin signaling. Disruption of the mouse homolog of the gene encoding PTP-1B yielded healthy mice that, in the fed state, had blood glucose concentrations that were slightly lower and concentrations of circulating insulin that were one-half those of their PTP-1B+/+ littermates. The enhanced insulin sensitivity of the PTP-1B-/- mice was also evident in glucose and insulin tolerance tests. The PTP-1B-/- mice showed increased phosphorylation of the insulin receptor in liver and muscle tissue after insulin injection in comparison to PTP-1B+/+ mice. On a high-fat diet, the PTP-1B-/- and PTP-1B+/- mice were resistant to weight gain and remained insulin sensitive, whereas the PTP-1B+/+ mice rapidly gained weight and became insulin resistant. These results demonstrate that PTP-1B has a major role in modulating both insulin sensitivity and fuel metabolism, thereby establishing it as a potential therapeutic target in the treatment of type 2 diabetes and obesity.     

Two morphologically distinct blood-brain barriers preventing entry of cytochrome c into cerebrospinal fluid

After intravenous injection, cytochrome c does not enter the cerebrospinal fluid. In most areas of the brain, the marker is prevented from leaving cerebral vessels by the capillary endothelium. In the choroid plexus, the marker passes freely out of capillaries into the extracellular space. However, it does not traverse tight junctions between epithelial cells and is rapidly incorporated into mnembrane-bound vesicles within the cell cytoplasm. Thereafter, cytochrome c is apparently removed by lysosomal degradation. These data suggest that there are at least two morphologically distinct blood-brain barriers to cytochrome c and that pinocytosis may be a mechanism for intracellular degradation rather than transcellular transport.     

Insulin: carrier potential for enzyme and drug therapy

Several carrier systems and targeting agents have been considered as means of delivering enzymes and drugs to specific tissues or cells. In this report insulin is shown to be effective in delivering enzyme-albumin conjugates to cells and tissues rich in insulin receptors. The complex is transported into cells by a process that resembles receptor-mediated endocytosis and can be identified in a lysosomal fraction. The enzyme-albumin-insulin complex retains its enzymatic activity and its ability to bind antibodies to insulin. It also has a hypoglycemic effect; however, plasma glucose concentrations can be maintained by glucose administration.     

Meteorological analysis of the eruption of soufriere in april 1979

Meteorological upper-air data, in conjunction with satellite imagery, lidar light detection and ranging returns, and aircraft sampling, aid in the determination of plume altitude and transport. The estimated trajectories indicate that the ash was transported eastward across the Atlantic to Africa in 3 to 5 days and that there was modest meridional transport as far as 15 degrees poleward during the first week of travel.     

Induction of pancreatic differentiation by signals from blood vessels

Blood vessels supply developing organs with metabolic sustenance. Here, we demonstrate a role for blood vessels as a source of developmental signals during pancreatic organogenesis. In vitro experiments with embryonic mouse tissues demonstrate that blood vessel endothelium induces insulin expression in isolated endoderm. Removal of the dorsal aorta in Xenopus laevis embryos results in the failure of insulin expression in vivo. Furthermore, using transgenic mice, we show that ectopic vascularization in the posterior foregut leads to ectopic insulin expression and islet hyperplasia. These results indicate that vessels not only provide metabolic sustenance, but also provide inductive signals for organ development.