Demonstration of Right and Left Atrial Dissociation by Atrial Rapid Pacing or Extrastimulation During Fast-Slow (Uncommon) Form of Atrioventricular Nodal Reentrant Tachycardia

Some recent works suggest that extranodal atrial fibers may form part of the reenlry circuit in the atrioventricular (AV) nodal reentrant tachycardia (AVNRT). This hypothesis is based on the fact that the perinodal dissection successfully abolished AVNRT while preserving intact AV conduction. Apart from the surgical success, the electrophysiological evidence supporting this hypothesis has not been demonstrated, especially in the uncommon (fast-slow) form of AVNRT. We present some electrophysiological evidence suggesting atrial participation in eight patients with the fast-slow form of AVNRT. During the tachycardia, rapid pacing or extrastimulation was done from the orifice of the coronary sinus (CS) and the right atrium (RA), while recording the electrograms of the CS and the low septal RA. In seven patients, right and left atrial dissociation was demonstrated during pacing from the RA, while in the remaining one this was demonstrated from the CS. The interatrial dissociation will be unlikely if the intranodal reentry circuit connects with the atria via a single upper common pathway. This suggests that the upper turnaround of the reentry circuit involves atrial tissue and that the extranodal accessory pathway with long conduction times may form the ascending limb of the circuit (atrionodal reentry). Alternatively, the reentry circuit is entirely intranodal and two or more connecting pathways are present between the atria and the circuit.     

Chrome congestive heart failure: Radiofrequency ablation of accessory pathways: implications of accumulated experience and time dedicated to procedures

Previous reports on radiofrequency ablation of accessory pathwayshave shown that the experience of the operator is of crucialimportance in reducing fluoroscopy time and achieving highersuccess rates. However, a detailed analysis of this importantissue has not been previously attempted We analysed 71 consecutive ablation procedures undertaken atSt George's Hospital by the same electrophysiology group andalways with the same first operator. Of all procedures, 66 (916%)were successful, as judged by abolition of accessory pathwayconduction without recurrence within the next 24 h. Failuresincluded two out of 38 left-sided pathway procedures (5·3%),one out of 11 intermediate septal (9·1%) and four outof 22 right-sided pathway procedures (18·2%). These differencewere not statistically significant. Average procedure and screeningtimes for all procedures were 162·9±86·0min and 56·8±48·2 mm respectively, whereasthe median of the number of discharges was 12, ranging fromone to 51. There was no significant difference between pathwaygroups or between concealed and non-concealed pathways in respectto procedure and screening time or number of discharges. Therewas a significant tendency towards decreased procedure and screeningtimes with accwnulating experience and this was similar forall pathway groups. There was also a tendency towards improvedcwnulative success rates with time dedicated to procedures. We conclude that a certain amount of ablation experience isrequired, even by experienced electrophysiologists, before arelatively high success rate without long radiation exposurecan be achieved, regardless of the location or the mode of conductionof the pathway. Success rates increase with procedure time,suggesting that early abandonment of the procedure may resultin higher failure rates in diffcult cases.     

维生素E琥珀酸酯诱导人胃腺癌细胞凋亡途径

目的　探讨维生素E琥珀酸酯 (VES)诱导人胃腺癌SGC -790 1细胞凋亡的死亡受体 (Fas)信号转导途径。方法　人胃腺癌SGC -790 1细胞经不同剂量VES(5,10 ,2 0 μg/ml)处理 ,同时做琥珀酸、维生素E和空白对照 ,采用DAPI(4,6-贰脒基 -2 -苯基吲哚 )荧光染色法观察细胞凋亡情况 ,用WesternBlot法检测Fas、带有死亡结构域的Fas相关蛋白 (FADD)和天冬氨酸特异性半胱氨酸蛋白酶 (caspase -8)蛋白表达情况 ,Fas和FADD反义寡聚核苷分别转染SGC -790 1细胞后 ,用荧光法检测caspase -8活性。 结果　经VES处理后的细胞DAPI染色可见凋亡的形态学改变 ,2 0 μg/mlVES处理 48h后的细胞凋亡率为 89.6% ;VES处理 48h后Fas、FADD和caspase -8蛋白表达明显增加 ,且呈剂量 -效应关系 ;阻断Fas可明显抑制FADD蛋白表达 ,Fas和FADD反义寡聚核苷转染细胞后caspase -8活性明显降低 (P <0 .0 1) ,其中阻断Fas的效果高于阻断FADD。结论　维生素E琥珀酸酯诱导人胃腺癌SGC -790 1细胞凋亡过程中启动了Fas信号转导途径 ,VES启动Fas后 ,FADD将Fas和caspase -8联接起来 ,活化caspases级联反应 ,从而构成Fas/FADD/caspase -8的凋亡信号途径     

Histamine differentially interacts with tumor necrosis factor-α and thrombin in endothelial tissue factor induction: the role of c-Jun NH2-terminal kinase

BACKGROUND: Histamine plays an important role in vascular disease. Tissue factor (TF) expression is induced in vascular inflammation and acute coronary syndromes. OBJECTIVES: This study examined the effect of histamine on tumor necrosis factor-alpha- (TNF-alpha-) vs. thrombin-induced endothelial TF expression. METHODS AND RESULTS: Histamine (10(-8)-10(-5) mol L-1), TNF-alpha (5 ng mL-1), and thrombin (1 U mL-1) induced TF expression in human endothelial cells. Although TF expression by TNF-alpha and thrombin was identical, histamine augmented TNF-alpha-induced expression 7.0-fold, but thrombin-induced expression only 2.6-fold. Similar responses occurred with TF activity. The H1-receptor antagonist mepyramine abrogated these effects. Differential augmentation by histamine was also observed at the mRNA level. Histamine-induced p38 activation preceded a weak second activation to both TNF-alpha and thrombin. Histamine-induced c-Jun NH2-terminal kinase (JNK) activation was followed by a strong second activation to TNF-alpha, and less to thrombin. Selective inhibition of this second JNK activation by SP600125 reduced TF induction to histamine plus TNF-alpha by 67%, but to histamine plus thrombin by only 32%. Histamine augmented TNF-alpha- and thrombin-induced vascular cell adhesion molecule 1 (VCAM-1) expression to a similar extent. Consistent with this observation, VCAM-1 induction to TNF-alpha and thrombin was mediated by p38, but not by JNK. CONCLUSIONS: Histamine differentially augments TNF-alpha- vs. thrombin-induced TF expression and activity, which is mediated by the H1-receptor, occurs at the mRNA level, and is related to differential JNK activation.     

Total and free tissue factor pathway inhibitor in pregnancy hypertension.

OBJECTIVE: To clarify the role played by tissue factor pathway inhibitor (TFPI) in pregnancy hypertension. METHODS: Using enzyme-linked immunosorbent assays, hemostatic measurements were obtained for women with pre-eclampsia (n=51), nonproteinuric hypertension of pregnancy (n=62), postpartum pre-eclampsia 24 h after childbirth (n=31), and no hypertension (healthy pregnant controls, n=100). RESULTS: There was a significant increase in circulating free TFPI levels in women with pre-eclampsia (9.7+/-6.2 ng/mL) or nonproteinuric hypertension of pregnancy (8.3+/-5.3 ng/mL) compared with healthy controls (5.3+/-2.1 ng/mL). In women with pre-eclampsia the levels remained elevated after placental delivery (10.6+/-4.0 ng/mL). Free protein S levels were significantly higher in women with pre-eclampsia (40.0%+/-10.7%), nonproteinuric hypertension of pregnancy (37.1%+/-12.5%), or postpartum pre-eclampsia (39.3%+/-9.1%) than in healthy pregnant controls (32.2%+/-8.5%). CONCLUSION: Increased levels of the physiologically active free forms of TFPI and free protein S, 2 coagulation inhibitors, may protect women with pregnancy-induced hypertension from the risks of hemostatic activation.     

白细胞介素6、信号传导和转录活化因子3和血管内皮生长因子在人脑胶质瘤中的表达及相关性研究

目的研究人脑不同级别胶质瘤中白细胞介素（IL）-6，信号传导和转录活化因子3（STAT3）和血管内皮生长因子（VEGF）的表达，探讨IL-6、STAT3和VEGF与肿瘤病理级别和侵袭性的关系。方法采用免疫组织化学法，检测70例人脑胶质瘤，10例脑膜瘤和5例正常脑组织中IL-6、STAT3和VEGF的表达。结果胶质瘤中IL-6、STAT3和VEGF的表达水平在高级别组（Ⅲ、Ⅳ级）明显高于低级别组（Ⅰ、Ⅱ级），两组间差异有统计学意义（P〈0．01），STAT3的表达与IL-6和VEGF的表达均呈正相关（P〈0．01）。结论IL-6、STAT3和VEGF的表达与胶质瘤的恶性程度有密切关系；且三者协同在胶质瘤发生、发展过程中起重要作用。三者的相关性证实VEGF基因由STAT3蛋白调节，而STAT3又由IL-6刺激活化。     

肿瘤蛋白质组学在信号传导通路、肿瘤标志物等方面的研究

肿瘤是一个多因素的疾病 ,在其的发生、发展过程中 ,分子生物学事件的复杂性日益受到人们的重视。随着基因组全序列测定的完成 ,蛋白质组学的研究得到了广泛的关注。应用蛋白质组学的方法 ,可以对细胞生长、分化过程中的蛋白质与细胞信号传导通路上的蛋白质之间的相互作用进行更为深入的研究 ,因而有希望发现控制肿瘤生物学行为的诸多蛋白质和信号分子。     

介导感觉生理功能的瞬时受体电位通道蛋白(TRP)家族研究进展

瞬时受体电位通道蛋白(TRP)家族由一类特殊的阳离子通道蛋白组成,在神经细胞及其他非兴奋细胞中有重要作用,其中在介导多种感觉生理功能方面的作用尤其显著.TRP结构与功能的深入研究为阐明感觉生理功能的分子机制提供了重要线索.本文综述TRP家族在温度感受、机械刺激感受、光感受和化学信号感受等方面的研究进展.     

The striatal-enriched protein tyrosine phosphatase gates long-term potentiation and fear memory in the lateral amygdala.

BACKGROUND: Formation of long-term memories is critically dependent on extracellular-regulated kinase (ERK) signaling. Activation of the ERK pathway by the sequential recruitment of mitogen-activated protein kinases is well understood. In contrast, the proteins that inactivate this pathway are not as well characterized. METHODS: Here we tested the hypothesis that the brain-specific striatal-enriched protein tyrosine phosphatase (STEP) plays a key role in neuroplasticity and fear memory formation by its ability to regulate ERK1/2 activation. RESULTS: STEP co-localizes with the ERKs within neurons of the lateral amygdala. A substrate-trapping STEP protein binds to the ERKs and prevents their nuclear translocation after glutamate stimulation in primary cell cultures. Administration of TAT-STEP into the lateral amygdala (LA) disrupts long-term potentiation (LTP) and selectively disrupts fear memory consolidation. Fear conditioning induces a biphasic activation of ERK1/2 in the LA with an initial activation within 5 minutes of training, a return to baseline levels by 15 minutes, and an increase again at 1 hour. In addition, fear conditioning results in the de novo translation of STEP. Inhibitors of ERK1/2 activation or of protein translation block the synthesis of STEP within the LA after fear conditioning. CONCLUSIONS: Together, these data imply a role for STEP in experience-dependent plasticity and suggest that STEP modulates the activation of ERK1/2 during amygdala-dependent memory formation. The regulation of emotional memory by modulating STEP activity may represent a target for the treatment of psychiatric disorders such as posttraumatic stress disorder (PTSD), panic, and anxiety disorders.