In Vivo Anergized T Cells Form Altered Immunological Synapses In Vitro

T cells contact allogeneic antigen presenting cells (APCs) and assemble, at their contact interface, a molecular platform called the immunological synapse. Synapse-based molecules provide directional signals for the T cell--either positive signals, resulting in T-cell activation, or negative signals causing T-cell inactivation or anergy. To better understand the molecular basis of in vivo T-cell anergy we analyzed the contacts made between in vivo anergized T cells and APCs, and determined which signaling molecules were included or excluded from their immunological synapses. Anergy was induced in TCR transgenic mice by the intravenous injection of semiallogeneic donor spleen cells. T cells from anergized mice were mixed with APCs, the T-cell/APC synapses imaged using deconvolution microscopy, and their molecular compositions were determined. T cells from anergic mice formed unstable immunological synapses in vitro with allogeneic APCs and failed to recruit the signaling proteins necessary to initiate T-cell activation. These findings suggest that T-cell anergy induced by exposure to semiallogeneic donor cells is associated with defects in the earliest events of T-cell activation, immunological synapse formation and recruitment of TCR-mediated signaling proteins.     

Fat-Derived Hormone Adiponectin Combined with FTY720 Significantly Improves Small-for-Size Fatty Liver Graft Survival

Owing to the discrepancy between organ donation and the demand for liver transplantation, expanding the liver donor pool is of vital importance. However, marginal liver grafts, such as small-for-size and/or fatty grafts, were associated with primary graft nonfunction or poor function. Therefore, novel combination therapies to rescue small-for-size fatty liver grafts should be investigated. In this study, we applied a combination therapy using a fat-derived hormone adiponectin (anti-steatosis) plus immunomodulator FTY720 (anti-inflammatory) in a rat liver transplantation model using small-for-size fatty liver grafts, and investigated the underlying protective mechanism such as anti-steatosis, intra-graft energy metabolism, hepatic microcirculatory changes, cell signaling cascades for survival, apoptosis and inflammation. The current study demonstrated that even a single treatment of adiponectin or FTY720 improved the 7-day graft survival from 0% to 62.5% (p = 0.001). The combination therapy significantly increased the 7-day graft survival rate to 100% by remarkable attenuation of graft steatosis and acute phase inflammatory response, significant activation of cell survival Akt pathway and maintenance of intra-graft adenosine triphosphate metabolism and improvement of hepatic microcirculation. In conclusion, the fat-derived hormone adiponectin combined with FTY720 might be a novel combination drug therapy for prevention of small-for-size fatty liver graft injury.     

Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose: a simple analysis by 13C NMR of urinary menthol glucuronide.

Menthol glucuronide was isolated from the urine of a healthy 70-kg female subject following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-(13)C]glucose. Glucuronide (13)C-excess enrichment levels were 4-6% and thus provided high signal-to-noise ratios (SNRs) for confident assignment of (13)C-(13)C spin-coupled multiplet components within each (13)C resonance by (13)C NMR. The [U-(13)C]glucuronide isotopomer derived via direct pathway conversion of [U-(13)C]glucose to [U-(13)C]UDP-glucose was resolved from [1,2,3-(13)C(3)]- and [1,2-(13)C(2)]glucuronide isotopomers derived via Cori cycle or indirect pathway metabolism of [U-(13)C]glucose. In a second study, a group of four overnight-fasted patients (63 +/- 10 kg) with severe heart failure were given peppermint oil and infused with [U-(13)C]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min constant infusion) resulting in a steady-state plasma [U-(13)C]glucose enrichment of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide (13)C-isotopomers were analyzed by (13)C NMR. [U-(13)C]glucuronide enrichment was 0.6% +/- 0.1%, and the sum of [1,2,3-(13)C(3)] and [1,2-(13)C(2)]glucuronide enrichments was 0.9% +/- 0.2%. From these data, flux of plasma glucose to hepatic UDPG was estimated to be 15% +/- 4% that of endogenous glucose production (EGP), and the Cori cycle accounted for at least 32% +/- 10% of GP.     

The 12‐Lead ECG in Patients with Mahaim Fibers

The aim of this review article is to discuss the electrocardiographic presentation of the so called variants of pre‐excitation (“Mahaim fibers”) during sinus rhythm and tachycardia.     

旁道位置与室上性心动过速首次发作时年龄及性别的关系探讨

目的为了解旁道位置与室上性心动过速初次发作时年龄及性别的关系.方法对128例已进行过射频消融的患者进行了回顾性分析.结果男性左侧旁道发病时平均年龄大于右侧及中隔旁道平均为14岁和9岁;大于女性左侧旁道7岁,男性显性旁道发病时平均年龄小于隐匿性旁道7岁.而女性显性旁道与隐匿性旁道、左侧旁道与右侧旁道发病时平均年龄无显著性差异.结论旁道位置与室上速初次发作时年龄及性别有关.     

Radiofrequency Catheter Ablation of the Anterosuperior and Posteroinferior Atrial Approaches to the AV Node for Treatment of AV Nodal Reentrant Tachycardia

Catheter Ablation Techniques in AVNRT. Radiofrequency catheter ablation has been established as a first-line curative treatment modality in patients with symptomatic AV nodal reentrant tachycardia (AVNRT). The successful sites of stepwise catheter ablation approaches of the so-called fast and slow pathways strongly suggest that AVNRT involves the atrial approaches to the AV node. The typical fast pathway ablation sites are located anterosuperior toward the apex of the triangle of Koch, which also contains the compact AV node, whereas the usual slow pathway ablation sites are located posteroinferior toward the base of the triangle of Koch at a greater distance to the compact AV node and bundle of His. Accordingly, ablation studies with large patient cohorts have demonstrated that fast pathway ablation carries a higher risk of inadvertent complete AV block. Thus, the slow pathway is clearly the primary target site, and fast pathway ablation is rarely necessary. Different approaches for slow pathway ablation have been elaborated: anatomically oriented stepwise techniques, ablation guided by double potentials recorded within the area of the slow pathway insertion, and combined techniques. The modern concept of AVNRT suggests that this arrhythmia involves the highly complex three-dimensional nonuniform anisotropic AV junctional area. Accordingly, mapping and ablation studies demonstrated that the anterior approach is not identical with fast pathway ablation, and the posterior approach is not identical with slow pathway ablation. Therefore, it is essential for interventional electrophysiologists to familiarize themsdves with the anatomic and electrophysiologic details of this complex and variable specialized AV junctional region. In this review, the anatomic and pathophysiologic aspects of the AV junctional area as they relate to interventional therapy are summarized briefly, and the catheter techniques for ablation of the so-called fast and slow AV nodal pathways for the treatment of AVNRT are described.     

血清补体系统在流行性出血热患者中的变化及其意义

应用单向免疫扩散法测定了流行性出血热(EHF)患者的7种补体成份和血浆素原(Pg).结果表明,CT脂酶抑制剂在少尿期、多尿期和恢复期均高于正常(P<0.01);补体C_1q在多尿期高于正常(P<0.01);补体C_4在发热期和少尿期低于正常(P<0.01),以后逐渐恢复正常;补体C_3,C_5和C_9的变化与C_4相似;B因子在少尿期低于正常(P<0.01),在多尿期高于正常(P<0.05);Pg始终高于正常水平但在少尿期有回降.说明EHF患者不仅有补体经典途径的识别阶段、活化阶段和膜攻击阶段的变化,而且亦有旁路激活,其活化程度与病情有关.     

卒中临床路径实施概述

文章介绍和总结了国外目前卒中临床路径实施的概况，包括临床路径的简介、卒中临床路径的模式、实施效果（优点及存在的问题）以及卒中临床路径的制订。     

Pheophytin a, a low molecular weight compound found in the marine brown alga Sargassum fulvellum, promotes the differentiation of PC12 cells

We identified and characterized a neurodifferentiation compound from the marine brown alga Sargassum fulvellum collected from the Japanese coastline. Several instrumental analyses revealed the compound to be pheophytin a. Pheophytin a did not itself promote neurite outgrowth of PC12 cells. However, when PC12 cells were treated with a low concentration of pheophytin a (3.9 microg/ml) in the presence of a low level of nerve growth factor (10 ng/ml), the compound produced neurite outgrowth similar to that produced by a high level of nerve growth factor (50 ng/ml). Pheophytin a also enhanced signal transduction in the mitogen-activated protein kinase signaling pathway, which is also induced by nerve growth factor. The effect of pheophytin a on neurite outgrowth of PC12 cells was completely blocked by U0126, a representative mitogen-activated protein kinase kinase inhibitor. These results suggest that pheophytin a enhances the neurodifferentiation of PC12 cells in the presence of a low level of nerve growth factor and that this effect is mediated by activation of a mitogen-activated protein kinase signaling pathway.