Neural cell adhesion molecule (NCAM-/-) null mice show impaired sensitization of the startle response

The neural cell adhesion molecule (NCAM) plays important roles in development of the nervous system and in synaptic plasticity and memory formation in the adult. The present study sought to further investigate the role of NCAM in learning by testing habituation and footshock sensitization learning of the startle response (SR) in NCAM null mutant (NCAM-/-) and wildtype littermate (NCAM+/+) mice. Whereas habituation is a form of non-associative learning, footshock sensitization is induced by rapid contextual fear conditioning. Habituation was tested by repetitive presentation of acoustic and tactile startle stimuli. Although NCAM-/- mice showed differences in sensitivity in both stimulus modalities, habituation learning was intact in NCAM-/- mice, suggesting that NCAM does not play a role in the mechanisms underlying synaptic plasticity in the startle pathway. Footshock sensitization was elicited by presentation of electric footshocks between two series of acoustic stimuli. In contrast to habituation, footshock sensitization learning was attenuated in NCAM-/- mice: the acoustic SR increase after the footshocks was lower in the mutant than in wildtype mice, indicating that NCAM plays an important role in the relevant brain areas, such as amygdala and/or the hippocampus.     

Change In Cycle Length During Narrow Complex Tachycardia: What Is The Mechanism?

Major spontaneous variation in cycle length during supraventricular tachycardia is quite an uncommon phenomenon, which sometimes can mislead a correct diagnosis. We describe a patient who developed spontaneous variation in cycle length during electrophysiologic study in whom the coronary sinus cannulation was extremely difficult. In this situation, careful inspection of the mechanisms associated with this variation and classic pacing maneuvers are important to make a correct diagnosis of the supraventricular tachycardia.     

Premature Ventricular Contractions and Non-sustained Ventricular Tachycardia: Association with Sudden Cardiac Death,Risk Stratification,and Management Strategies

Premature ventricular contractions (PVCs) and non-sustained ventricular tachycardia (NSVT) are frequently encountered and a marker of electrocardiomyopathy. In some instances, they increase the risk for sustained ventricular tachycardia, ventricular fibrillation, and sudden cardiac death. While often associated with a primary cardiomyopathy, they have also been known to cause tachycardia-induced cardiomyopathy in patients without preceding structural heart disease. Medical therapy including beta-blockers and class III anti-arrhythmic agents can be effective while implantable cardiac defibrillators (ICD) are indicated in certain patients. Radiofrequency ablation (RFA) is the preferred, definitive treatment in those patients that improve with anti-arrhythmic therapy, have tachycardia-induced cardiomyopathy, or have certain subtypes of PVCs/NSVT. We present a review of PVCs and NSVT coupled with case presentations on RFA of fascicular ventricular tachycardia, left-ventricular outflow tract ventricular tachycardia, and Purkinje arrhythmia leading to polymorphic ventricular tachycardia.     

Division of labor: Subsets of dorsal-appendage-forming cells control the shape of the entire tube

The function of an organ relies on its form, which in turn depends on the individual shapes of the cells that create it and the interactions between them. Despite remarkable progress in the field of developmental biology, how cells collaborate to make a tissue remains an unsolved mystery. To investigate the mechanisms that determine organ structure, we are studying the cells that form the dorsal appendages (DAs) of the Drosophila melanogaster eggshell. These cells consist of two differentially patterned subtypes: roof cells, which form the outward-facing roof of the lumen, and floor cells, which dive underneath the roof cells to seal off the floor of the tube. In this paper, we present three lines of evidence that reveal a further stratification of the DA-forming epithelium. Laser ablation of only a few cells in the anterior of the region causes a disproportionately severe shortening of the appendage. Genetic alteration through the twin peaks allele of tramtrack69 (ttk^twk), a female-sterile mutation that leads to severely shortened DAs, causes no such shortening when removed from a majority of the DA-forming cells, but rather, produces short appendages only when removed from cells in the very anterior of the tube-forming tissue. Additionally we show that heterotrimeric G-protein function is required for DA morphogenesis. Like TTK69, Gβ13F is not required in all DA-forming follicle cells but only in the floor and leading roof cells. The different phenotypes that result from removal of Gβ13F from each region demonstrate a striking division of function between different DA-forming cells. Gβ mutant floor cells are unable to control the width of the appendage while Gβ mutant leading roof cells fail to direct the elongation of the appendage and the convergent-extension of the roof-cell population.     

The PPARγ ligand ciglitazone regulates androgen receptor activation differently in androgen-dependent versus androgen-independent human prostate cancer cells

The androgen receptor (AR) regulates growth and progression of androgen-dependent as well as androgen-independent prostate cancer cells. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have been reported to reduce AR activation in androgen-dependent LNCaP prostate cancer cells. To determine whether PPARγ ligands are equally effective at inhibiting AR activity in androgen-independent prostate cancer, we examined the effect of the PPARγ ligands ciglitazone and rosiglitazone on C4-2 cells, an androgen- independent derivative of the LNCaP cell line. Luciferase-based reporter assays and Western blot analysis demonstrated that PPARγ ligand reduced dihydrotestosterone (DHT)-induced increases in AR activity in LNCaP cells. However, in C4-2 cells, these compounds increased DHT-induced AR driven luciferase activity. In addition, ciglitazone did not significantly alter DHT-mediated increases in prostate specific antigen (PSA) protein or mRNA levels within C4-2 cells. siRNA-based experiments demonstrated that the ciglitazone-induced regulation of AR activity observed in C4-2 cells was dependent on the presence of PPARγ. Furthermore, overexpression of the AR corepressor cyclin D1 inhibited the ability of ciglitazone to induce AR luciferase activity in C4-2 cells. Thus, our data suggest that both PPARγ and cyclin D1 levels influence the ability of ciglitazone to differentially regulate AR signaling in androgen-independent C4-2 prostate cancer cells.     

Laser-scanning lithography (LSL) for the soft lithographic patterning of cell-adhesive self-assembled monolayers

We report the development of laser-scanning lithography (LSL), which employs a laser-scanning confocal microscope to pattern photoresists that can be utilized, for example, in the fabrication of masters for use in soft lithography. This convenient technique provides even exposure across the entire view field and facilitates accurate alignment of successive photoresist exposures. Features on the scale of 3 microm have been achieved to date with a 10x objective (NA 0.45). Virtual masks, instructions for laser irradiation, were drawn using the Region of Interest (ROI) function of a Zeiss LSM 510 microscope. These regions were then exposed to a 458 nm argon laser for 32 micros (0.9 mW/microm(2)). Differential interference contrast (DIC) imaging was utilized with a non-destructive 514 nm argon laser as an immediate quality check of each exposure, to align successive exposures, and to reduce chromatic aberration between imaging and exposure. Developed masters were replica-molded with poly(dimethylsiloxane) (PDMS); these masters were then utilized for microcontact printing of cell-adhesive self-assembled monolayers (SAMs) to demonstrate the utility of this process. Initial studies confirmed that human dermal fibroblast adhesion and spreading were limited to cell-adhesive SAM areas. LSL is a rapid, flexible, and readily available technique that will accelerate master design and preparation; moreover, it can be applied to additional forms of photolithography and photopolymerization for studies in cell biology, biomaterials design and evaluation, materials science, and surface chemistry.     

胃癌肝转移术中射频消融治疗的临床意义

目的：评估胃癌根治术同时性射频消融治疗在治疗胃癌肝转移的临床意义。方法：收集2008年1月至2010年12月19例胃癌肝转移患者,合计转移灶33个,转移灶小于4厘米,且合计不超过4个转移灶。射频消融治疗在术中超声引导下完成。Kap-lan—Meier法分析无病生存期,无肝转移生存期及总生存期。对临床病理学因子及肝转移相关因子采用Log-rank法Cox风险比例模型解析。结果：中位无病生存、无肝转移生存及总生存期为355,394及488天。有3例患者获得长期的无复发生存。单因素分析显示,较早的T分期、N分期,较少的转移灶数量,较小的转移灶直径与良好的预后相关。多因素分析提示,病灶数量与病灶直径为独立预后因子。结论：肝转移射频消融治疗安全性好,对单发的小于4cm转移灶,以及多发病灶合计直径小于4cm者射频消融治疗较为适用,可有显著生存获益。部分患者可迭临床治愈。对于胃癌肝转移的合适病例,射频消融治疗值得推广。     

Catheter ablation of ventricular tachycardia originating from the left posterior papillary muscle guided by the shadow of a multipolar catheter

A 62-year-old man without structural heart disease underwent electrophysiological testing for ventricular tachycardia (VT). Hemodynamically unstable VT was induced after isoproterenol (ISP) provocation. Electroanatomical mapping using a multipolar catheter identified the earliest activation originating from the posterior papillary muscle (PPM) where prepotentials preceding the local ventricular electrogram were observed. Irrigated radiofrequency current guided by the shadow of a multipolar catheter eliminated the VT. This case suggested that multipolar catheters may be helpful for identifying tachycardia origins arising from the PPM.     

A linear ablating system in the left and right atrium: feasibility, catheter performance and clinical results

IntroductionWe describe the use of a ablating system to compartmentalise and regionally isolate the atria in paroxysmal and persistent atrial fibrillation (AF).Methods40 patients were studied, 25 paroxysmal AF and 14 persistent AF. One patient enrolled was later found to be in left atrial flutter and was excluded. The Cardima Revelation® TX catheter system with Intellitemp® Radiofrequency (RF) energy control device and a Medtronic Atakar® RF generator were used to place wide area circumferential ablations to achieve conduction block into the left and right sided pulmonary veins. Roof lines and mitral isthmus lines were also performed. In patients with persistent AF and in repeat procedures, right atrial compartmentalisation was performed with an anterior superior vena cava (SVC) to inferior vena cava (IVC) line and a septal SVC to IVC line.ResultsAt 6 months, 18 of the 39 patients were asymptomatic, 10 had improved symptoms and 22 were in sinus rhythm. In the paroxysmal group, 11 were asymptomatic, 7 had improved symptoms and 16 (64%) were in sinus rhythm. In the persistent group, 7 were asymptomatic, 3 had improved symptoms and 6 (43%) were in sinus rhythm. The total group AF burden was 37.8 ± 5.4 hrs pre-procedure and 23.1 ± 5.1 hrs at 6 months post procedure. Mean temperature, impedance and power recorded at each pole demonstrated effective power delivery at all poles. No catheter charring was observed, complication rates were comparable to standard AF ablation technique.ConclusionLinear ablation in the left and right atria to mimic Cox’s Maze is feasible and safe using this ablating system.