BACKGROUND & AIMS: These experiments were designed to determine whether glycogenolysis was influenced by the glycogen concentration of vascular smooth muscle. Segments of hog carotid artery smooth muscle were allowed to synthesize variable amounts of 1-[13C]glucosyl units of glycogen. Artery segments were then isometrically contracted in the presence of 2-[13C]glucose. Prior to and after isometric contraction, measurements were made of tissue glycogen content and superfusate glucose and lactate concentrations. 2-[13C]Lactate and 3-[13C]lactate peak intensities in the superfusate were measured using 13C-NMR spectroscopy. The tissue glycogen content decreased exponentially during the 4.5 h of isometric contraction (R2 = 0.990), despite more than a 3-fold range of glycogen concentration prior to contraction. The extent of glycogen utilization during a 3 h isometric contraction varied linearly with the precontraction glycogen concentration (R2 = 0.727). Lactate production specifically from glycogen breakdown increased with an increase in precontraction glycogen concentration (R2 = 0.620). During a 3 h isometric contraction neither the glucose utilization (R2 = 0.007) nor lactate production specifically produced from glucose (R2 = 0.00002) varied with the precontraction glycogen concentration. It is concluded that the rate of glycogenolysis is determined by the content of glycogen during prolonged contractions. In addition, precontraction glycogen levels influence the pathway for glycogen utilization but not the pathway for glucose utilization. Therefore, glycolysis and glycogenolysis behave independently in vascular smooth muscle.

背景与目标： 这些实验旨在确定糖原分解是否受血管平滑肌糖原浓度的影响。允许猪颈动脉平滑肌段合成可变量的1-[13C] 糖原葡萄糖单元。然后在2-[13C] 葡萄糖存在下等距收缩动脉段。在等距收缩之前和之后，测量组织糖原含量和超融合物葡萄糖和乳酸浓度。使用13C-NMR光谱测量超融合物中的2-[13C] 乳酸和3-[13C] 乳酸峰强度。组织糖原含量在等距收缩的4.5小时内呈指数下降 (R2 = 0.990)，尽管收缩前糖原浓度超过3倍。在3 h等距收缩期间糖原利用的程度随收缩前糖原浓度线性变化 (R2 = 0.727)。糖原分解产生的乳酸产量随着收缩前糖原浓度的增加而增加 (R2 = 0.620)。3小时的等距收缩葡萄糖利用率 (R2 = 0.007) 和特别由葡萄糖产生的乳酸产量 (R2 = 0.00002) 都不随收缩前糖原浓度而变化。结论是糖原分解速率由长期收缩期间糖原含量决定。此外，收缩前糖原水平会影响糖原利用的途径，但不会影响葡萄糖利用的途径。因此，糖酵解和糖原分解在血管平滑肌中独立运作。

BACKGROUND & AIMS: Although reductions in neurotransmission have been reported in response to agonist-mediated adenosine A1 receptor activation, the implications of A2 receptor activation on synaptic transmission have not been well explored. We examined the role adenosine A2 receptors play in the efficacy of neurotransmission between the Schaffer collateral-CA1 pathway in the rat transverse hippocampal slice. A2 receptor blockade in the presence of complete A1 receptor inhibition led to a reversible reduction of the field excitatory post-synaptic potential (EPSP) slope in response to low-frequency test pulses (0.033 Hz) indicating that A2 receptors can enhance synaptic transmission. A2 receptor blockade by the A2 antagonist, DMPX (3,7-dimethyl-1-propargylxanthine) prevented the induction of tetanus-induced long-term potentiation (LTP) of the EPSP. In contrast, no such effect on LTP induction was observed during A1 receptor blockade. We also examined the effects of DMPX on the induction of LTP during continued A1 receptor blockade with CPT. Under this condition, LTP was significantly reduced when compared to LTP induced in the presence of CPT alone. A similar result was found using the highly polar A2 antagonist 8-SPT (8-(p-sulfophenyl)theophylline) suggesting that the effects of DMPX on LTP were not due to a direct action on an intracellular intermediate. DMPX had no effect on LTP expression if applied 45 min following the tetanus indicating that A2 receptors play no significant role in the maintenance phase of LTP. Selective A2a receptor activation did not alter the field EPSP. Similarly, selective blockade of the A2a receptor did not interfere with tetanus-induced LTP. Increases in neuronal firing rates can result in elevations in the concentration of extracellular adenosine. Together, these results suggest that the A2 receptors may play an important role in the induction although not the maintenance of hippocampal LTP and that the effect is likely to be mediated by the A2b receptor.

背景与目标： 尽管据报道，由于激动剂介导的腺苷A1受体激活，神经传递减少，但A2受体激活对突触传递的影响尚未得到很好的探讨。我们检查了腺苷A2受体在大鼠横海马切片中Schaffer collateral-CA1途径之间的神经传递功效中的作用。在完全A1受体抑制的存在下，A2受体阻断导致场兴奋性突触后电位 (EPSP) 斜率响应于低频测试脉冲 (0.033Hz) 的可逆降低，表明A2受体可以增强突触传递。A2拮抗剂DMPX (3,7-二甲基-1-炔基黄嘌呤) 对A2受体的阻断阻止了破伤风诱导的EPSP长期增强 (LTP) 的诱导。相反，在A1受体阻滞期间未观察到对LTP诱导的这种作用。我们还研究了在CPT持续阻断A1受体期间DMPX对LTP诱导的影响。在这种情况下，与单独在CPT存在下诱导的LTP相比，LTP显着降低。使用高度极性的A2拮抗剂8-SPT (8-(对磺苯基) 茶碱) 发现了类似的结果，表明DMPX对LTP的作用不是由于对细胞内中间体的直接作用。如果在破伤风后45分钟使用DMPX，则表明A2受体对LTP表达没有影响在LTP的维持阶段没有重要作用。选择性A2a受体激活不会改变EPSP。同样，选择性阻断A2a受体不会干扰破伤风诱导的LTP。神经元放电速率的增加会导致细胞外腺苷浓度的升高。这些结果表明，A2受体可能在诱导中起重要作用，尽管不是维持海马LTP，并且该作用可能是由A2b受体介导的。

BACKGROUND & AIMS: Interleukin-1beta (IL-1beta) is closely involved in liver disorders. IL-1beta produces nitric oxide (NO) in vascular smooth muscle cells and relaxes vascular smooth muscle via cyclic guanosine 3',5'-monophosphate (cGMP). In this study, we evaluated the relaxing effect of IL-1beta on cultured Ito cells. Ito cells were isolated from the livers of male Wistar rats and cultured for 24 hours. Immunolocalization of inducible nitric oxide synthase (iNOS) and cGMP and intensity of fluorescence of cGMP were examined using a confocal laser microscope. Ito cells were treated with 0, 200, and 1,000 pmol/L IL-1beta, and the intracellular cGMP concentration was measured after 12 hours. Moreover, Ito cells treated with 200 and 1,000 pmol/L IL-1beta and not treated with IL-1beta were observed over 12 hours, and the area of the same Ito cell was compared before and after the addition of IL-1beta. Next, effects of N(G)-monomethyl-L-arginine (L-NMMA) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) on Ito cell relaxation by IL-1beta treatment were examined. In Ito cells, immunofluorescence of iNOS was observed, and fluorescent intensity of cGMP increased after addition of IL-1beta. Intracellular cGMP concentration increased dose-dependently after addition of IL-1beta. Cell area significantly increased in the IL-1beta-treated group compared with the untreated group. Relaxation of Ito cells by IL-1beta treatment was inhibited by L-NMMA in a dose-dependent manner, but was enhanced by SNAP. These results indicate that IL-1beta produces NO in cultured Ito cells and relaxes the cells via cGMP.

背景与目标： Interleukin-1beta (IL-1beta) 与肝脏疾病密切相关。IL-1beta在血管平滑肌细胞中产生一氧化氮 (NO)，并通过环鸟苷3 '，5'-单磷酸 (cGMP) 松弛血管平滑肌。在这项研究中，我们评估了IL-1beta对培养的Ito细胞的松弛作用。从雄性Wistar大鼠的肝脏中分离Ito细胞，并培养24小时。使用共聚焦激光显微镜检查诱导型一氧化氮合酶 (iNOS) 和cGMP的免疫定位以及cGMP的荧光强度。Ito细胞用0、200和1,000 pmol/L IL-1beta处理，12小时后测定细胞内cGMP浓度。此外，在12小时内观察到用200和1,000 pmol/L IL-1beta处理和不用IL-1beta处理的Ito细胞，并比较在添加IL-1beta前后相同Ito细胞的面积。接下来，通过IL-1beta处理检查了N(G)-单甲基-L-精氨酸 (L-NMMA) 和S-亚硝基-N-乙酰基-DL-青霉胺 (SNAP) 对Ito细胞松弛的影响。在Ito细胞中，观察到iNOS的免疫荧光，加入IL-1beta后cGMP的荧光强度增加。加入IL-1beta后，细胞内cGMP浓度呈剂量依赖性增加。与未处理组相比，IL-1beta-treated组的细胞面积显着增加。IL-1beta处理对Ito细胞的松弛以剂量依赖性方式被l-nmma抑制，但被SNAP增强。这些结果表明，IL-1beta在培养的Ito细胞中产生NO，并通过cGMP使细胞松弛。

BACKGROUND & AIMS: :Continuous changes in the length of smooth muscles require a highly organized sarcolemmal structure. Yet, smooth muscle cells also adapt rapidly to altered environmental cues. Their sarcolemmal plasticity must lead to profound changes which affect transmembrane signal transduction as well as contractility. We have established porcine vascular and human visceral smooth muscle cultures of epithelioid and spindle-shaped morphology and determined their plasma membrane properties. Epithelioid cells from both sources contain a higher ratio of cholesterol to glycerophospholipids, and express a less diverse range of lipid-associated annexins. These findings point to a reduction in efficiency of membrane segregation in epithelioid cells. Moreover, compared to spindle-shaped cells, cholesterol is more readily extracted from epithelioid cells with methyl-beta-cyclodextrin and its synthesis is more susceptible to inhibition with lovastatin. The inability of epithelioid cells to process vasoactive metabolites, such as angiotensin or nucleotides further indicates that contractile properties are impaired. Phenotypic plasticity extends beyond the loss of smooth muscle cell marker genes. The plasma membrane has undergone profound functional changes which are incompatible with cyclic foreshortening, but might be important in the development of vascular disease.

背景与目标： : 平滑肌长度的持续变化需要高度组织化的肌膜结构。然而，平滑肌细胞也迅速适应改变的环境线索。它们的肌膜可塑性必须导致深刻的变化，从而影响跨膜信号转导以及收缩力。我们已经建立了上皮样和纺锤形形态的猪血管和人内脏平滑肌培养物，并确定了它们的质膜特性。来自两种来源的上皮样细胞均含有较高的胆固醇与甘油磷脂比例，并且表达与脂质相关的膜联蛋白的范围较少。这些发现表明上皮样细胞的膜分离效率降低。此外，与纺锤形细胞相比，胆固醇更容易从上皮样细胞中提取甲基-β-环糊精，其合成更容易受到洛伐他汀的抑制。上皮样细胞无法处理血管活性代谢产物，例如血管紧张素或核苷酸，进一步表明收缩特性受损。表型可塑性超出了平滑肌细胞标记基因的丧失。质膜发生了深刻的功能变化，与循环缩短不相容，但在血管疾病的发展中可能很重要。

BACKGROUND & AIMS: CD4+ anti-tumor T cells reactive with rat adenocarcinoma 13762 kill tumor in vitro and cause regression of tumor in vivo. The role of various host immune cells in CD4+ T-cell-mediated tumor elimination in vivo was investigated by adoptive transfer of anti-tumor T cell clones to recipients that were selectively depleted of individual immune cell types. By these means, macrophages and NK cells were found to be required for tumor killing. Depletion of host CD4+ T cells, CD8+ T cells, or neutrophils was without effect on tumor elimination by anti-tumor T cells. An essential role for antigen receptor-negative NK cells is likely dependent upon secretion of IFN-gamma from NK cells since treatment of tumor recipients with anti-IFN-gamma antibody prior to adoptive transfer and tumor challenge abrogated T cell killing, resulting in progressive tumor growth. Viability of adenocarcinoma 13762 or anti-tumor T cells was unaffected by treatment with either IFN-gamma or anti-IFN-gamma antibody in vitro, but cell surface MHC class II expression was induced in tumor cells by exposure to IFN-gamma. In addition, tumor cells were isolated from tumor-bearing animals by absorption using anti-MHC class II antibody, demonstrating that 13762 tumor expresses cell surface MHC class II antigens in situ. However, if hosts were depleted of NK cells before tumor challenge, MHC class II+ tumor was not recovered. Collectively these results suggest that adenocarcinoma 13762 is eliminated by MHC class II-restricted CD4+ T cells by direct tumor killing.

背景与目标： 与大鼠腺癌反应的CD4 + 抗肿瘤T细胞13762在体外杀伤肿瘤并在体内引起肿瘤的消退。通过将抗肿瘤T细胞克隆过继转移到选择性耗尽个体免疫细胞类型的受体，研究了各种宿主免疫细胞在体内CD4 T细胞介导的肿瘤消除中的作用。通过这些方法，发现巨噬细胞和NK细胞是杀死肿瘤所必需的。宿主CD4 T细胞，CD8 T细胞或中性粒细胞的耗竭对抗肿瘤T细胞消除肿瘤没有影响。抗原受体阴性NK细胞的重要作用可能取决于NK细胞中IFN-γ 的分泌，因为在过继转移和肿瘤挑战之前用抗IFN-γ 抗体治疗肿瘤接受者消除了T细胞杀伤，导致进行性肿瘤生长。腺癌13762或抗肿瘤T细胞的活力在体外不受IFN-γ 或抗IFN-γ 抗体治疗的影响，但细胞表面mhcii类表达通过暴露于IFN-γ 在肿瘤细胞中诱导。此外，通过使用抗MHC II类抗体吸收从荷瘤动物中分离肿瘤细胞，证明13762肿瘤原位表达细胞表面MHC II类抗原。但是，如果宿主在肿瘤激发之前耗尽了NK细胞，则MHC II类肿瘤将无法恢复。这些结果共同表明，通过直接杀伤肿瘤，MHC II类限制性CD4 T细胞消除了腺癌13762。

BACKGROUND & AIMS: :The oxidative deamination of serotonin (5-HT) to 5-hydroxyindoleacetic acid (5-HIAA) by rat primary astrocyte cultures was investigated in intact cells using HPLC. All detectable 5-HIAA accumulated in the extracellular medium, and its rate of production was proportional to the 5-HT concentration over the tested range of 5 x 10(-7) to 10(-4) M. At 5 x 10(-7) M 5-HT, intracellular 5-HT was detectable only in astrocytes treated with monoamine oxidase (MAO) inhibitors. These findings are consistent with the idea that 5-HT taken up into astrocytes is not stored for re-release, but is rapidly metabolized to 5-HIAA, which is then extruded from the cell. At 5 x 10(-7) M 5-HT, 5-HIAA formation in intact cells was blocked 63% by the selective high-affinity 5-HT uptake inhibitor fluoxetine. 5-HT oxidation to 5-HIAA is carried out principally by MAO-A, because clorgyline was more effective at inhibiting the production of 5-HIAA than was pargyline. Radioenzymatic determinations of MAO activity in cell homogenates supported these findings, because under these conditions clorgyline was 1,000-fold more effective than pargyline at inhibiting MAO activity toward 14C-labelled 5-HT. However, the relatively selective MAO-B substrate beta-phenylethylamine (PEA) was also oxidized, showing that these cultures also contained MAO-B activity; the Km values for MAO-A oxidation of 5-HT and MAO-B oxidation of PEA were 135 and 45 microM, and Vmax values were 88 and 91 nmol/mg of total cell protein/h, respectively. Higher concentrations of PEA (greater than 20 microM) were oxidized by both MAO-A and MAO-B isozymes.(ABSTRACT TRUNCATED AT 250 WORDS)

背景与目标： : 使用HPLC在完整细胞中研究了大鼠原代星形胶质细胞培养物将5-羟色胺 (5-HT) 氧化脱氨为5-羟基吲哚乙酸 (5-HIAA)。所有可检测到的5-HIAA都积累在细胞外培养基中，在5x10(-7) 至10(-4) M的测试范围内，其产生速率与5-HT浓度成正比。在5x10(-7) M 5-HT时，仅在用单胺氧化酶 (MAO) 抑制剂处理的星形胶质细胞中可检测到细胞内5-HT。这些发现与以下观点一致: 摄取到星形胶质细胞中的5-HT不会储存以重新释放，而是会迅速代谢为5-HIAA，然后从细胞中挤出。在5 × 10(-7) m5-ht时，选择性高亲和力5-HT摄取抑制剂氟西汀63% 阻断完整细胞中的5-HIAA形成。5-HT氧化为5-HIAA主要由MAO-A进行，因为clorgyline比pargyline更有效地抑制5-HIAA的产生。细胞匀浆中MAO活性的放射酶测定支持了这些发现，因为在这些条件下，clorgyline在抑制针对14c标记的5-HT的MAO活性方面比pargyline有效1,000倍。然而，相对选择性的MAO-B底物 β-苯乙胺 (PEA) 也被氧化，表明这些培养物也含有MAO-B活性; 5-HT的MAO-A氧化和PEA的MAO-B氧化的Km值分别为135和45微米，vmax值分别为88和91 nmol/mg的总细胞蛋白/h。较高浓度的豌豆 (大于20微米) 被MAO-A和MAO-B同工酶氧化。(摘要截短于250字)

BACKGROUND & AIMS: :The mode of action of Vibrio vulnificus haemolysin (VVH) on mast cells from the peritoneal cavity of the rat was examined. VVH induced histamine release, and damage to the mast cells, in a dose-dependent fashion. When 1 microgram of VVH was added to c. 10(5) mast cells at 37 degrees C, histamine release was observed after a lag period of 5-10 s, and was complete within 5 min. The action was temperature-dependent, and was not induced at 4 degrees C. Disodium cromoglycate, a membrane stabiliser for mast cells, inhibited the histamine release significantly, but the effect was not dose-dependent. Moreover, leakage of lactate dehydrogenase from VVH-treated mast cells was observed. These results suggest that VVH acts on the cell membrane of mast cells and is cytolytic.

背景与目标： : 检查了创伤弧菌溶血素 (VVH) 对大鼠腹膜腔肥大细胞的作用方式。VVH以剂量依赖性方式诱导组胺释放并损害肥大细胞。当在37 ℃ 下将1微克VVH加入c. 10(5) 肥大细胞时，在5-10 s的滞后期后观察到组胺释放，并在5分钟内完成。该作用与温度有关，在4 ℃ 下未诱导。色甘氨酸二钠是肥大细胞的膜稳定剂，可显着抑制组胺的释放，但其作用不是剂量依赖性的。此外，观察到乳酸脱氢酶从VVH处理的肥大细胞中泄漏。这些结果表明，VVH作用于肥大细胞的细胞膜并具有溶细胞性。

BACKGROUND & AIMS: Neural activity is thought to play a significant role during the development of the cerebral cortex. In this study, we examined the effects of global activity block or enhancement and the effects of patterned firing on the ability of cultured rat neocortical neurons to survive during the second week in vitro, beyond the beginning of synaptogenesis. Blockade of neuronal activity by adding tetrodotoxin (TTX) and increasing magnesium concentration in the medium strongly reduced the survival of cortical cells. Increasing neuronal activity by raising the external potassium concentration significantly improved the survival of cortical neurons. We postulated that in a developing neuronal network the survival of nerve cells is regulated by synaptically mediated events that involve changes in the intracellular calcium concentration. To examine this question further, we monitored the activity of the developing network by optically recording the intracellular calcium signals of many neurons simultaneously. These recordings show that in low magnesium neocortical neurons express synchronized oscillation of their intracellular calcium concentration. The ability of a network to synchronize the changes in intracellular calcium of multiple cells appeared gradually during the second week in culture, paralleled by both an increase in the synaptic density and a decline in the number of surviving neurons. By examining the fate of identified cells several days after a recording session, we found that those nerve cells that were co-activated with other neurons had a significantly higher chance to survive than cells that did not participate in synchronized events. These experiments demonstrate that during early cortical network development cortical neurons show synchronized firing activity and that the survival of neurons is at least partially dependent on this pattern of neuronal activity.

背景与目标： 神经活动被认为在大脑皮层发育过程中起着重要作用。在这项研究中，我们研究了整体活动阻滞或增强的影响以及图案化放电对培养的大鼠新皮层神经元在体外第二周 (突触开始后) 存活的能力的影响。通过添加河豚毒素 (TTX) 和增加培养基中的镁浓度来阻断神经元活性，从而大大降低了皮质细胞的存活。通过提高外部钾浓度来增加神经元活性，显着改善了皮质神经元的存活。我们推测，在发育中的神经元网络中，神经细胞的存活受到突触介导的事件的调节，这些事件涉及细胞内钙浓度的变化。为了进一步研究这个问题，我们通过同时光学记录许多神经元的细胞内钙信号来监测发育网络的活动。这些记录表明，在低镁的新皮层神经元中，其细胞内钙浓度表达同步振荡。在培养的第二周，网络使多个细胞的细胞内钙的变化同步的能力逐渐出现，同时突触密度增加和存活神经元数量减少。通过在记录过程几天后检查已识别细胞的命运，我们发现与其他神经元共同激活的神经细胞比不参与同步事件的细胞存活的机会要高得多。这些实验表明，在早期皮质网络发育过程中，皮质神经元显示出同步的放电活动，并且神经元的存活至少部分取决于这种神经元活动模式。

BACKGROUND & AIMS: :The effects of colorectal distension (CRD) were examined on neurons located in and around the nucleus submedius (Sm) in the medial thalamus of urethane-anesthetized rats. A total of 66 units (49 in the Sm and 17 in immediately surrounding regions) responding to cutaneous pinch were tested to examine their responsiveness to the CRD. All the neurons that responded to cutaneous stimulation were nociceptive specific (NS) neurons. Based on their responses to the CRD the Sm neurons were classified into three types as follows: 23 (47%) of 49 neurons in the Sm and three (18%) of 17 neurons near the Sm had tonic excitatory responses with long-lasting after-discharges (type I); nine (18%) Sm neurons and four (24%) peri-Sm neurons were tonically excited but had no after-discharge (type II); and seven (14%) Sm neurons were inhibited (type III). Ten (20%) Sm neurons and 10 (59%) peri-Sm neurons did not respond to CRD. All the excitatory and inhibitory responses to CRD increased with increasing CRD pressure. Simultaneous application of CRD and cutaneous pinch did not produce a reduced response (nocigenic inhibition). These results demonstrate that most of the Sm neurons receive convergent viscerosomatic inputs from the colon and/or rectum and from the skin, suggesting that the Sm may participate in visceral nociception.

背景与目标： : 检查了大肠扩张 (CRD) 对氨基甲酸乙酯麻醉大鼠内侧丘脑中中核 (Sm) 及其周围神经元的影响。测试了对皮肤挤压有反应的总共66个单位 (Sm中有49个，周围区域中有17个)，以检查它们对CRD的反应能力。所有对皮肤刺激有反应的神经元都是伤害性特异性 (NS) 神经元。根据对CRD的反应，Sm神经元分为三种类型: Sm中49个神经元中的23个 (47% 个) 和Sm附近的17个神经元中的3个 (18% 个) 具有强直兴奋反应，放电后持续时间长 (I型); 九个 (18%) Sm神经元和四个 (24%) 周围Sm神经元被音调兴奋，但没有放电后 (II型); 七个 (14%) Sm神经元被抑制 (III型)。10个 (20%) Sm神经元和10个 (59%) 周围Sm神经元对CRD没有反应。随着CRD压力的增加，对CRD的所有兴奋和抑制反应均增加。同时应用CRD和皮肤捏合不会产生降低的反应 (抑制)。这些结果表明，大多数Sm神经元从结肠和/或直肠以及皮肤接收会聚的内脏体输入，表明Sm可能参与内脏伤害感受。

BACKGROUND & AIMS: :The failure of lesioned axons to regenerate over long distances in the mammalian central nervous system (CNS) is not due to an inability of central neurons to regenerate, but rather to the non-permissive nature of the CNS tissue environment. Regenerating CNS axons, which grow well within a peripheral nerve, for example, fail to penetrate mature CNS tissue by more than about 1 mm. Recent evidence indicates that this may be due to inhibitory membrane proteins associated with CNS oligodendrocytes and myelin. We report here that human telencephalic neuroblasts implanted into the excitotoxically lesioned striatum of adult rats can escape or neutralize this inhibitory influence of the adult CNS environment and extend axons along major myelinated fibre tracts for distances of up to approximately 20 mm. The axons were seen to elongate along the paths of the striato-nigral and cortico-spinal tracts to reach the substantia nigra, the pontine nuclei and the cervical spinal cord, which are the normal targets for the striatal and cortical projection neurons likely to be present in these implants.

背景与目标： : 受损的轴突在哺乳动物中枢神经系统 (CNS) 中无法长距离再生不是由于中枢神经元无法再生，而是由于CNS组织环境的非宽松性质。例如，在周围神经内良好生长的再生CNS轴突不能穿透成熟的CNS组织超过约1毫米。最近的证据表明，这可能是由于与CNS少突胶质细胞和髓磷脂相关的抑制性膜蛋白所致。我们在此报告，植入成年大鼠兴奋性毒性病变纹状体的人类端脑神经母细胞可以逃避或中和成年CNS环境的这种抑制作用，并沿主要有髓纤维束延伸轴突，距离可达约20毫米。可以看到轴突沿着纹状体-黑质和皮质-脊髓束的路径伸长，到达黑质，桥脑核和颈脊髓，这是纹状体和皮质投射神经元的正常目标。这些植入物。

BACKGROUND & AIMS: BACKGROUND:Angiotensin-converting enzyme (ACE) inhibitors prevent the expansion and rupture of aortic aneurysms in animals. We investigated the association between ACE inhibitors and rupture in patients with abdominal aortic aneurysms. METHODS:We did a population-based case-control study of linked administrative databases in Ontario, Canada. The sample included consecutive patients older than 65 (n=15,326) admitted to hospital with a primary diagnosis of ruptured or intact abdominal aortic aneurysm between April 1, 1992, and April 1, 2002. FINDINGS:Patients who received ACE inhibitors before admission were significantly less likely to present with ruptured aneurysm (odds ratio [OR] 0.82, 95% CI 0.74-0.90) than those who did not receive ACE inhibitors. Adjustment for demographic characteristics, risk factors for rupture, comorbidities, contraindications to ACE inhibitors, measures of health-care use, and aneurysm screening yielded similar results (0.83, 0.73-0.95). Consistent findings were noted in subgroups at high risk of rupture, including patients older than 75 years and those with a history of hypertension. Conversely, such protective associations were not observed for beta blockers (1.02, 0.89-1.17), calcium channel blockers (1.01, 0.89-1.14), alpha blockers (1.15, 0.86-1.54), angiotensin receptor blockers (1.24, 0.71-2.18), or thiazide diuretics (0.91, 0.78-1.07). INTERPRETATION:ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm, unlike other antihypertensive agents. Randomised trials of ACE inhibitors for prevention of aortic rupture might be warranted.

背景与目标：

BACKGROUND & AIMS: :An immediately inducible gene by gonadotropin was isolated from rat ovaries primed with pregnant mare serum gonadotropin (PMSG) by using a subtraction cloning procedure. Homology analysis revealed that the gene is a rat homologue of scavenger receptor class B-I, which was recently identified as a specific receptor for high density lipoprotein (HDL). The structure of rat SRBI was determined by nucleotide sequence analysis of full-length cDNAs for SRBI. Northern blot analysis revealed that rat SRBI mRNA levels were rapidly and strongly increased within 3 h by the injection of PMSG. In situ hybridization study revealed that SRBI mRNA was strongly induced in theca interna cells of immature rat ovary stimulated with 30 IU of PMSG for 6 h. SRBI mRNA expression was also observed in corpora lutea of the adult rat ovary. These findings indicate that expression of SRBI mRNA is restricted to and induced in the ovarian steroidogenic cell types where cholesterol is used as a substrate for synthesis of steroid hormones. Our data strongly suggest that SRBI may play a significant role in the ovarian steroidogenesis by mediating selective uptake of cholesterol from HDL to ovarian theca interna cells or to corpus luteum.

背景与目标： : 使用减法克隆程序从用妊娠母马血清促性腺激素 (PMSG) 引发的大鼠卵巢中分离出促性腺激素立即诱导的基因。同源性分析表明，该基因是清道夫受体B-I类的大鼠同源物，最近被鉴定为高密度脂蛋白 (HDL) 的特异性受体。通过SRBI全长cdna的核苷酸序列分析确定大鼠SRBI的结构。Northern印迹分析显示，通过注射PMSG，大鼠SRBI mRNA水平在3小时内迅速且强烈地增加。原位杂交研究表明，用30 IU的PMSG刺激6 h，在未成熟大鼠卵巢的卵泡膜细胞中强烈诱导SRBI mRNA。在成年大鼠卵巢的黄体中也观察到了SRBI mRNA的表达。这些发现表明，SRBI mRNA的表达仅限于并在其中胆固醇用作合成类固醇激素的底物的卵巢类固醇生成细胞类型中诱导。我们的数据强烈表明，SRBI可能通过介导胆固醇从HDL到卵巢卵泡膜细胞或黄体的选择性摄取而在卵巢类固醇生成中起重要作用。

BACKGROUND & AIMS: :It is well-recognised that steady-state isometric muscle force is decreased following active shortening (force depression, FD) and increased following active stretch (force enhancement, FE). It has also been demonstrated that passive muscle force is increased following active stretch (passive FE). Several studies have reported that FD increases with shortening amplitude and that FE and passive FE increase with stretch amplitude. Here, we investigate whether these trends continue with further increases in shortening or stretch amplitude. Experiments were performed using in situ cat soleus muscles (n=8 for FD; n=7 for FE and passive FE). FD, FE and passive FE were measured after shortening or stretch contractions that covered as wide a range of amplitudes as practically possible without damaging the muscles. FD increased approximately linearly with shortening amplitude, over the full range of amplitudes investigated. This is consistent with the hypothesis that FD arises from a stress-induced inhibition of crossbridges. FE increased with stretch amplitude only up to a point, and then levelled off. Passive FE, and the transient increase in force at the end of stretch, showed relationships to stretch amplitude that were qualitatively very similar to the relationship for FE, increasing only until the same critical stretch amplitude had been reached. We conclude that FE and passive FE do not increase with stretch amplitude under all circumstances. This finding has important consequences for determining the mechanisms underlying FE and passive FE because any mechanism that is proposed to explain them must be able to predict it.

背景与目标： : 众所周知，主动缩短 (力降低，FD) 后，稳态等距肌肉力降低，主动拉伸 (力增强，FE) 后，稳态等距肌肉力增加。还已证明，主动拉伸 (被动FE) 后，被动肌肉力量会增加。一些研究报告说，FD随缩短幅度而增加，FE和被动FE随拉伸幅度而增加。在这里，我们研究这些趋势是否随着缩短或拉伸幅度的进一步增加而继续。使用原位猫比目鱼肌进行实验 (FD为n = 8; FE和被动FE为n = 7)。在缩短或拉伸收缩后测量FD，FE和被动FE，这些收缩实际上覆盖了尽可能宽的振幅范围，而不会损坏肌肉。在所研究的整个振幅范围内，FD随振幅的缩短而近似线性增加。这与FD由应力诱导的交叉桥抑制引起的假设是一致的。FE仅随拉伸幅度增加到一个点，然后趋于平稳。被动FE和拉伸结束时的瞬时力增加显示出与拉伸幅度的关系，在质量上与FE的关系非常相似，仅在达到相同的临界拉伸幅度之前才增加。我们得出的结论是，在所有情况下，FE和被动FE都不会随拉伸幅度而增加。这一发现对于确定FE和被动FE的潜在机制具有重要的影响，因为提出的任何解释它们的机制都必须能够预测它。

BACKGROUND & AIMS: :Angiostensin II (Ang II) regulates the migration and proliferation of vascular smooth muscle cells. Recent studies indicate that intermediate-conductance Ca2+ -activated K+ (IKca) channels have an important role in cell migration and proliferation. It is not known, however, whether the action of Ang II is linked to IKca channel regulation. Here, we investigated the modulation of IKca channels by Ang II in artery smooth muscle cells. Functional IKca channel expression in cultured embryonic rat aorta smooth muscle (A10) cells was studied using the patch-clamp technique. These cells predominantly express IKca channels. In contrast, large-conductance Ca2+ -activated K+ (BKca) currents were rarely observed in excised patches. Ang II increased the IKca current in a contration-dependent manner. Losartan (1.0 microM), an AT1 selective antagonist, abolished the activation of IKca channels by Ang II. Pretreatment with 100 microM myristoylated protein kinase C inhibitor peptide 20-28 or 10 microM GF109203X completely abolished the AngII-induced activation of IKca currents, whereas the action of Ang II was not prevented in the presence of 100 microM Rp-cyclic 3', 5'-hydrogen phosphotiate adenosine triethylammonium, a protein kinase A inhibitor, or 1.0 microM KT-5823, a protein kinase G inhibitor. A membrane permeant analogue of diacylglycerol 1, 2-dioctanoyl-sn-glycerol (10 microM) induced the activation of IKca currents. These data suggest that Ang II activates IKca channels through the activation of protein kinase C, and the AT1 receptor is involved in the regulation of these channels.

背景与目标： : Angiostensin II (Ang II) 调节血管平滑肌细胞的迁移和增殖。最近的研究表明，中间电导Ca2激活的K (IKca) 通道在细胞迁移和增殖中起重要作用。但是，尚不清楚Ang II的作用是否与IKca通道调节有关。在这里，我们研究了Ang II对动脉平滑肌细胞中IKca通道的调节。使用膜片钳技术研究了培养的胚胎大鼠主动脉平滑肌 (A10) 细胞中功能性IKca通道的表达。这些细胞主要表达IKca通道。相反，在切除的贴片中很少观察到大电导Ca2激活的K (BKca) 电流。Ang II以依赖于收缩的方式增加了IKca电流。氯沙坦 (1.0 microM)，一种AT1选择性拮抗剂，通过Ang II消除了IKca通道的激活。用100 microM肉豆蔻酰化蛋白激酶C抑制剂肽20-28或10 microM GF109203X进行预处理完全消除了AngII诱导的IKca电流的激活，而在存在100 microM Rp-环状3 '，5'-磷酸氢腺苷三乙基铵的情况下，Ang II的作用没有被阻止，蛋白激酶a抑制剂，或1.0 microM KT-5823，蛋白激酶G抑制剂。二酰基甘油1,2-二酰基-sn-甘油 (10 microM) 的膜渗透类似物诱导了IKca电流的激活。这些数据表明Ang II通过激活蛋白激酶C激活IKca通道，AT1受体参与了这些通道的调节。

BACKGROUND & AIMS: Expression of genes coding for ubiquitin and heatshock protein (hsp) 70 were examined by in situ hybridization using a rat model with permanent occlusion of the distal middle cerebral artery (MCA). Only polyubiquitin (UbC) mRNA increased markedly following ischaemia in the central zone of the MCA territory of the neocortex. UbC gene expression reached the maximum level 4 h post-occlusion and remained elevated at 24 h. UbC expression was retarded slightly compared with that of the hsp70 gene. UbB and Ub-S30 were expressed at almost similar levels in both the ischaemic and non-ischaemic hemispheres. These results indicated that UbC probably has the most stress-inducible characteristics among the three ubiquitin genes.

背景与目标： 使用具有远端大脑中动脉 (MCA) 永久闭塞的大鼠模型，通过原位杂交检查了编码泛素和热休克蛋白 (hsp) 70的基因的表达。在新大脑皮层MCA区域的中央区域发生缺血后，只有聚泛素 (UbC) mRNA显着增加。UbC基因表达在闭塞后4小时达到最大水平，并在24小时保持升高。与hsp70基因相比，UbC表达略有延迟。在缺血性和非缺血性半球中，UbB和Ub-S30的表达水平几乎相似。这些结果表明，在三个泛素基因中，UbC可能具有最易受胁迫诱导的特征。