bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in Repolarization Properties with Long‐Term Cardiac Memory Modify Dispersion of Repolarization in Patients with Wolff‐Parkinson‐White Syndrome
Authors: TAKADA YASUNOBU , INDEN YASUYA , AKAHOSHI MAKOTO , SHIBATA YOSHIHISA , SHIMIZU ATSUYA , YOSHIDA YUKIHIKO , YAMADA TAKUMI , TSUBOI NAOYA , HIRAYAMA HARUO , ITO TERUO , KONDO TAKAHISA , SAITO HIDEHIKO , HIRAI MAKOTO
Published: August 2003

Cardiac Memory Modifies Repolarization Dispersion.
Introduction: Transient T wave changes after cessation of preexcitation have been attributed to cardiac memory. However, there have been no reports on the effects of long‐term cardiac memory on repolarization dispersion before and after catheter ablation in patients with Wolff‐Parkinson‐White (WPW) syndrome.

Methods and Results: We investigated 47 patients with an accessory pathway (AP; 24 manifest left‐sided, 14 manifest right‐sided, and 9 concealed left‐sided). Repolarization dispersion was analyzed by two methods, recovery time (RT) dispersion and newly proposed T wave width (WT), from 87‐lead body surface maps before, 1 day after, and 7 days after catheter ablation. RT dispersion and WT were significantly correlated before, 1 day after, and 7 days after catheter ablation (r = 0.78). In patients with preexcitation, RT dispersion and WT increased significantly (P < 0.05) 1 day after catheter ablation (178 ± 32 msec and 172 ± 30 msec) compared with those before (154 ± 24 msec and 156 ± 18 msec) and 7 days after catheter ablation (147 ± 19 msec and 156 ± 16 msec), respectively. However, there were no significant changes in RT dispersion and WT before and after catheter ablation in concealed WPW syndrome.

Conclusion: The findings suggest that the abrupt changes in activation sequence increase repolarization dispersion in the presence of previous cardiac memory, and that the dispersion decreases days or weeks after alteration of activation sequence by catheter ablation, with development of new cardiac memory in patients with manifest WPW syndrome.
Adrenergic‐Cholinergic Interaction that Modulates Repolarization in the Atrium is Altered with Aging
Authors: SOSUNOV EUGENE A. , ANYUKHOVSKY EVGENY P. , ROSEN MICHAEL R.
Published: August 2003

Autonomic Modulation of Atrial Repolarization.
Introduction: Aging is associated with involution of both limbs of the autonomic nervous system, and the prejunctional and postjunctional effects of adrenergic and cholinergic stimulation are altered with senescence. Hence, postjunctional age‐related changes in adrenergic‐cholinergic interaction are a likely occurrence and may contribute to an altered substrate for arrhythmias.

Methods and Results: Microelectrode techniques were used to record action potentials from epicardial slices of Bachmann's bundles of dogs aged 3 to 5 years (adult) and 8 to 12 years (old) in the absence or presence of acetylcholine and isoproterenol (separately and in combination). In control, action potential duration to 90% repolarization (APD) was longer in old atria. Acetylcholine (10−8 to 10−5 mol/L) in a concentration‐dependent manner hyperpolarized and shortened APD in both tissues, with more prominent effects in the old. The effects of isoproterenol (10−9 to 10−6 mol/L) to elevate the plateau and shorten APD were about the same in both adult and old tissues. In adults, low concentrations of isoproterenol (10−9 and 10−8 mol/L) significantly prolonged APD, which had been first shortened by acetylcholine. This effect of isoproterenol was decreased in old atrial tissue, resulting in shorter APD in old than adult atria in the combined presence of beta‐adrenergic and muscarinic agonists. Conclusion: In adult Bachmann's bundle, beta‐adrenergic stimulation effectively operates as a “brake” to decrease the extent of cholinergic‐induced APD shortening. The action of beta‐adrenergic stimulation to antagonize acetylcholine‐induced acceleration of repolarization declines with age, which may contribute to an altered arrhythmogenic substrate.
Atrial Signal Analysis and Defibrillation Threshold Assessment in Chronic Persistent and Reinduced Atrial Fibrillation
Authors: BORIANI GIUSEPPE , BARTOLINI PIETRO , BIFFI MAURO , CALCAGNINI GIOVANNI , CAMANINI CLAUDIA , CORAZZA IVAN , ZANNOLI ROMANO , BARBARO VINCENZO , BRANZI ANGELO
Published: August 2003

De. brillation Threshold in Chronic and Reinduced AF.
Introduction: Induced versus spontaneous atrial fibrillation (AF) is of interest for assessing atrial defibrillation threshold reproducibility.

Methods and Results: Twenty‐one patients with chronic AF underwent internal cardioversion with assessment of atrial defibrillation threshold at baseline and at reinduced AF. High right atrial (HRA) and coronary sinus (CS) bipolar recordings were analyzed to measure the mean local atrial period, its coefficient of variation, the 5th (P5) and 95th (P95) percentiles of atrial intervals, and the percentage of points lying at the baseline (number of occurrences), and to quantify AF organization. Atrial defibrillation threshold was comparable in baseline and reinduced AF in terms of leading‐edge voltage and delivered energy. Baseline and reinduced AF were comparable with regard to overall signal parameters (both in HRA and CS) and the presence of an organized arrhythmia pattern. As for individual variables, P5 increased while P95 and coefficient of variation decreased in reinduced AF compared with spontaneous AF (statistical significance was achieved for all these parameters in HRA, but only for coefficient of variation and P95 in CS).

Conclusion: Sustained AF reinduced after cardioversion of chronic AF is comparable with baseline AF in terms of atrial defibrillation threshold, atrial cycle length, and pattern of organization. Therefore, a clinical model based on reinduction of sustained AF after cardioversion is suitable for studying the effects of a series of interventions on atrial defibrillation threshold. However, because this model does not yield a form of AF with comparable indices of local refractoriness (e.g., P5), it is not recommended when analyzing local electrophysiologic properties.
Mechanistic Significance of Intermittent Pulmonary Vein Tachycardia in Patients with Atrial Fibrillation
Authors: ORAL HAKAN , ÖZAYDIN MEHMET , TADA HIROSHI , CHUGH AMAN , SCHARF CHRISTOPH , HASSAN SOHAIL , LAI STEVE , GREENSTEIN RADMIRA , PELOSI FRANK , KNIGHT BRADLEY P. , STRICKBERGER S. ADAM , MORADY FRED
Published: August 2003

Pulmonary Vein Tachycardia.
Introduction: The significance of intermittent tachycardia within a pulmonary vein (PV) during an episode of atrial fibrillation (AF) is unclear. The aim of this study was to determine the role that intermittent PV tachycardias play in AF.

Methods and Results: In 56 patients with AF, segmental ostial ablation guided by PV potentials was performed to isolate the PVs. The characteristics of intermittent PV tachycardias and the inducibility of AF before and after PV isolation were analyzed prospectively. During AF, a PV tachycardia (mean cycle length 130 ± 30 msec) with exit block to the left atrium was present in 93% of left superior, 80% of left inferior, 73% of right superior, and 7% of right inferior PVs. The site of shortest cycle length during AF alternated between the PVs and left atrium 1 to 13 times per minute. Complete isolation was achieved in 168 (94%) of 178 targeted PVs. In 99% of PVs, tachycardia resolved upon isolation. AF was persistent before and after PV isolation in 100% and 27% of patients, respectively (P < 0.001).

Conclusion: Intermittent bursts of tachycardia are observed within multiple PVs during persistent AF in a majority of patients. After PV isolation, PV tachycardias almost always resolve, and AF is less likely to be inducible or persistent. These observations suggest a dynamic interplay between the atria and PVs, with intermittent bursts of PV tachycardia being dependent on left atrial input and with the probability of persistent AF diminishing when PV tachycardias are eliminated by PV isolation.
Implantable Cardioverter Defibrillator Sensing Failure Due to Endocardial R Wave Electrical Alternans
Authors: JONGNARANGSIN KRIT , MELA THEOFANIE
Published: August 2003

Electrical Alternans and ICD Undersensing. A 71‐year‐old patient underwent routine single‐chamber implantable cardioverter defibrillator (ICD) generator replacement. During defibrillation threshold testing, ventricular tachycardia was induced but the ICD failed twice to properly detect the tachycardia due to endocardial R wave alternans and sensing of every other beat. The problem was resolved by inserting a separate sensing/pacing lead positioned further away from the existing ICD lead.
Atrioventricular Nodal Reentrant Tachycardia with Ventriculoatrial Block and Unsuccessful Ablation of the Slow Pathway
Authors: CALÒ LEONARDO , LAMBERTI FILIPPO , CIOLLI ANDREA , SANTINI MASSIMO
Published: August 2003

AVNRT with VA Block. We report the case of failed slow pathway ablation in a woman with typical AV nodal reentrant tachycardia (AVNRT) and periods of Wenckebach‐like second‐degree VA block and 2:1 VA block. The occurrence of VA block during AVNRT suggests the upper turnaround point of the circuit is confined to the AV node. This supports the notion that, at least in some cases, the location of the reentrant circuit for AVNRT is completely in the compact AV node.
Body Surface Area of ST Elevation and the Presence of Late Potentials Correlate to the Inducibility of Ventricular Tachyarrhythmias in Brugada Syndrome
Authors: ECKARDT LARS , BRUNS HANS‐JÜRGEN , PAUL MATTHIAS , KIRCHHOF PAULUS , SCHULZE‐BAHR ERIC , WICHTER THOMAS , BREITHARDT GÜNTER , BORGGREFE MARTIN , HAVERKAMP WILHELM
Published: August 2003

BSPM and Late Potentials in Brugada Syndrome.
Introduction: The value of noninvasive markers reflecting repolarization and/or conduction abnormalities in identifying patients with abnormal ECG showing a pattern of atypical right bundle branch block and ST elevation syndrome (Brugada syndrome) at risk for life‐threatening arrhythmias is controversial. Because right precordial ST elevation reflects inhomogeneous repolarization, we hypothesized that a correlation between the area of ST elevation, that is, the area of inhomogeneous repolarization, and the inducibility of ventricular tachyarrhythmias (VT) exists. Therefore, the body surface area of ST elevation and the presence of late potentials were compared to the inducibility of VT in patients with the characteristic ECG of Brugada syndrome.

Methods and Results: A 120‐channel body surface potential map was recorded at rest and after administration of a Class I agent (ajmaline, 1 mg/kg) to measure the body surface area of ST elevation (≥0.2 mV) in 23 individuals (16 patients had been resuscitated from near sudden cardiac death or had suffered syncope) with an ECG compatible with the diagnosis of Brugada syndrome as well as in 15 healthy controls and in 15 patients with arrhythmogenic right ventricular cardiomyopathy. Late potentials were assessed in 20 of the Brugada patients using signal‐averaged ECG. Programmed ventricular stimulation was performed at two ventricular sites with up to three extrastimuli. Mean body surface area of ST elevation (≥0.2 mV) of all Brugada syndrome patients was 154 ± 139 cm2 (control 9 ± 9 cm2; P < 0.001). In the group of patients with arrhythmogenic right ventricular cardiomyopathy, only one patient was found to have an area of ST elevation (165 cm2). In the presence of ajmaline, area size increased to 330 ± 223 cm2 in Brugada syndrome patients (P < 0.05). In patients with inducible sustained (n = 15) and nonsustained VT (n = 3), a mean area of 183 ± 139 cm2 was found, whereas the area was only 52 ± 58 cm2 in those with no VT induction (P < 0.05). For an area ≥ 50 cm2, there were positive and negative predictive values of 92% and 60%, respectively. Positive late potentials were found in 60% of patients and correlated to the inducibility during programmed ventricular stimulation (positive predictive value 100%, negative predictive value 75%; P < 0.001).

Conclusion: In patients with Brugada syndrome, the body surface area of ST elevation and the presence of late potentials correlate to the inducibility of VT during programmed ventricular stimulation and may be of value as a new noninvasive marker for risk stratification in these patients.
Cerebrovascular Complication Associated with Pulmonary Vein Ablation
Authors: KOK LAI CHOW , MANGRUM J. MICHAEL , HAINES DAVID E. , MOUNSEY J. PAUL
Published: August 2003

Stroke and PV Ablation.
Introduction: Radiofrequency (RF) ablation has become an established treatment modality for patients with paroxysmal atrial fibrillation (AF). A principal limitation of RF catheter ablation is the risk of thromboembolism. Stroke as a complication after ablation of triggers of AF has not been previously reported.

Methods and Results: Fifty‐six patients underwent RF ablation for a focal source of AF. Forty‐nine patients (86%) had AF triggers in ≥1 pulmonary vein. Mean procedure time was 227 ± 74 minutes. Cerebrovascular event occurred in 3 (5%) patients, all >60 years old. Two of the three patients had a prior history of transient ischemic attacks.

Conclusion: The risk of stroke from RF ablation may be higher in paroxysmal AF patients with prior transient ischemic attack.
Exclusion of Fluoroscopy During Ablation Treatment of Right Accessory Pathway in Children
Authors: DRAGO FABRIZIO , SILVETTI MASSIMO STEFANO , DI PINO ALFREDO , GRUTTER GIORGIA , BEVILACQUA MAURIZIO , LEIBOVICH SHOSHANA
Published: August 2003

Electroanatomic Ablation of Accessory Pathways.
Introduction: The field of pediatric electrophysiology poses many challenges to electrophysiologists. In particular there are two major concerns: (1) to reduce the amount of fluoroscopy exposure to patients and medical staff in the catheterization laboratory and (2) to minimize the number of vascular accesses. Prolonged fluoroscopy times are associated with radiofrequency (RF) ablation of right accessory pathways (APs), particularly the right free‐wall AP. The aim of this study was to eliminate the use of fluoroscopy during treatment of right‐sided APs in children while using a single‐catheter approach.

Methods and Results: We studied 21 consecutive pediatric patients (mean age 11.3 ± 3.2 years) with Wolff‐Parkinson‐White syndrome due to a right AP. To limit fluoroscopy use, we used a three‐dimensional navigation system that facilitated reconstruction of a three‐dimensional electroanatomic activation map along the tricuspid annulus either on the atrial side during orthodromic AV reciprocating tachycardia or along the ventricular side during anterograde preexcitation. RF application was successful and without complications in 20 patients (success rate 95%); moreover, 19 of the 21 patients underwent a single‐catheter procedure. The remaining two patients required an additional quadripolar catheter for atrial stimulation. A mean of 2 ± 1 RF applications were used during the whole study.

Conclusion: Our study demonstrates that ablation of right APs in children can be performed without fluoroscopy using a single catheter with minimal amounts of RF applications. Our new technique is associated with high success rates.
Reduction of the Internal Atrial Defibrillation Threshold with Balanced Orthogonal Sequential Shocks
Authors: ZHENG XIANGSHENG , BENSER MICHAEL E. , WALCOTT GREGORY P. , SMITH WILLIAM M. , IDEKER RAYMOND E.
Published: August 2003

Reduction of Shock Strength with Balanced Sequential Shocks.
Introduction: The aim of this study was to determine the atrial defibrillation threshold (ADFT) of a first shock across the standard right atrium (RA) to distal coronary sinus (dCS) configuration followed by a second shock along the atrial septum with a standard sequential waveform (the second shock leading edge equaled the first shock trailing edge) and a balanced sequential waveform (the leading edges of both shocks were equal).

Methods and Results: In nine sheep atrial fibrillation was induced with acetyl‐β‐methylcholine and burst pacing. A catheter was placed with electrodes in the dCS, proximal coronary sinus (pCS), and RA. A J‐shaped catheter was positioned with an electrode at Bachmann's bundle (BB) while another catheter was positioned with an electrode in the superior vena cava (SVC). The ADFTs of six single‐ and dual‐pathway configurations were determined with single, standard sequential, or balanced sequential shocks. The ADFT of the RA→dCS configuration (0.86 ± 0.27 J, 159 ± 29 V, 2.42 ± 0.36 A) was significantly reduced when followed by an SVC→pCS (0.58 ± 0.17 J, 112 ± 20 V, 1.64 ± 0.39 A) or a BB→pCS shock (0.64 ± 0.16 J, 119 ± 18 V, 1.81 ± 0.38 A) with standard sequential shocks. With balanced sequential shocks, the peak voltage and current ADFTs were further significantly reduced (85 ± 11 V and 1.24 ± 0.21 A for second shock SVC→pCS, and 93 ± 13 V and 1.38 ± 0.27 A for second shock BB→pCS).

Conclusion: The ADFT of the standard RA→dCS shock is significantly reduced when followed by a second shock along the atrial septum delivered between electrodes in the pCS and either SVC or BB and ADFT is further reduced with balanced sequential shocks.
Regulation of Transient Outward Current in Human Atrial Myocytes by Protein Tyrosine Kinase Pathway
Authors: WANG YANGGAN , KUMAR RAJIV , WAGNER MARY B. , CHENG JUN , MISHRA MANJARI , JOYNER RONALD W.
Published: August 2003

Regulation of Transient Outward Current.
Introduction: Regulation of transient outward current (Ito) in human myocytes is unclear. The present study investigated the effect of protein tyrosine kinase (PTK) inhibitors on Ito in human atrial myocytes.

Methods and Results: Atrial myocytes were isolated enzymatically from biopsies of human right atrial appendage obtained from patients undergoing coronary artery bypass surgery. Ito was recorded by the whole‐cell patch‐clamp technique in voltage‐clamp configuration. Two groups of PTK inhibitors, the ATP binding site PTK inhibitors genistein and AG957 and the protein substrate PTK inhibitors ST638 and PP2, significantly inhibited Ito in a concentration‐dependent manner, with a potency order of genistein > AG957 > ST638 > PP2. At test pulse potential of +60 mV, Ito was inhibited by 28% ± 3%, 59% ± 3%, and 89% ± 3% by 15, 50, and 100 μM genistein, respectively. Daidzein and PP3, inactive analogues of genistein and PP2, respectively, did not produce any inhibitory effects on Ito. In addition to the inhibition of Ito amplitude, the protein substrate PTK inhibitors ST638 and PP2 significantly accelerated Ito inactivation (current decay) and delayed recovery from inactivation. Inhibition of protein tyrosine phosphatase partially reversed the effect of genistein. Stimulation or inhibition of serine/threonine kinases (PKA, PKC, and PKG) did not change Ito or alter the inhibitory response of PTK inhibitors on Ito.

Conclusion: In human atrial cells, the PTK pathway plays an important role in the regulation of basal Ito, independent of serine/threonine kinases.
Intracardiac Doppler Echocardiographic Quantification of Pulmonary Vein Flow Velocity: An Effective Technique for Monitoring Pulmonary Vein Ostia Narrowing During Focal Atrial Fibrillation Ablation
Authors: REN JIAN‐FANG , MARCHLINSKI FRANCIS E. , CALLANS DAVID J. , ZADO ERICA S.
Published: August 2003

Pulmonary Flow in AF.
Introduction: Ablation at the pulmonary vein (PV) ostium to isolate triggers for atrial fibrillation (AF) may induce PV narrowing. The AcuNav ultrasound catheter can image PV flow and quantify peak velocity and may be useful in assessing the degree of narrowing of PV ostia.

Methods and Results: In 93 patients with AF undergoing PV ostial ablation (up to 40 W, 52°C, 90 sec), the ultrasound catheter was placed in the right atrium and PV peak flow velocities were measured during systole and diastole before and after ablation. Ostial PV electrical isolation was achieved in 216 of the 219 targeted PVs. The ultrasound catheter provided flow imaging of all PVs. The ostial peak flow velocities measured 56 ± 12 cm/sec before ablation and increased to 101 ± 22 cm/sec after ablation (P < 0.001). Peak velocity > 100 cm/sec was detected in 103 (47%) of 219 and ≥ 158 cm/sec (estimated pressure gradient 10 mmHg) with turbulent flow features, in 7 (3.2%) of 219 PVs. The highest velocity detected in one PV was 211 cm/sec (17.7 mmHg). Follow‐up ultrasound catheter measurements were obtained in 13 patients (30 previously ablated PVs) during repeat ablations. The ostial peak velocity had decreased by 22 ± 14 cm/sec and in 25 (83%) of 30 PVs was within the baseline range (< 100 cm/sec) at a mean follow‐up of 4.9 ± 2.2 months. Follow‐up magnetic resonance imaging (MRI) or contrast‐enhanced CT was obtained at 7.0 ± 3.8 months in seven patients with PV velocity > 158 cm/sec after initial ablation. No significant stenosis (< 30%) was identified, and no patient suffered clinical symptoms (follow‐up 6–18 months) related to the described acute changes in PV flow after an initial ablation procedure. Of 13 patients with repeat ablation, two had PV velocities > 100 cm/sec before repeat ablation, and three PVs in two patients had flow velocity > 158 cm/sec after repeat ablation. One of these patients developed symptoms of exertional dyspnea; MRI at 4 months showed 50% to 60% ostial narrowing.

Conclusion: Ostial ablation for PV isolation may induce a mild‐to‐moderate increase in PV flow velocity, which can be identified using an ultrasound catheter with Doppler color flow imaging. Increases in PV flow velocity (< 158 cm/sec) after a primary ablation procedure appear to be well tolerated, and a return toward baseline flow characteristics should be anticipated by 3 months. A more cautious approach may be required for patients undergoing repeat PV isolation.
Postinfarction Risk Assessment for Sudden Cardiac Death Using Late Potential Analysis of the Digital Holter Electrocardiogram
Authors: STEINBIGLER PETER , HABERL RALPH , BRÜGGEMANN THOMAS , ANDRESEN DIETRICH , STEINBECK GERHARD
Published: August 2003

Digital Holter ECG Late Potential Analysis.
Introduction: Noninvasive postinfarction risk assessment for sudden cardiac death is limited. Standard analysis of the signal‐averaged QRS complex can identify patients at risk for monomorphic ventricular tachycardia, but its value for discriminating patients at risk for sudden death is low.

Methods and Results: The aim of this study was to prospectively investigate repeated late potential analysis of digital Holter ECG and compare it with standard analysis of the signal‐averaged QRS complex within a short ECG period and with common clinical risk factors for sudden cardiac death in 756 consecutive patients after acute myocardial infarction. Digital Holter ECG were subdivided into 5‐minute segments, and late potential analysis was performed on each 5‐minute segment. During follow‐up of 32 ± 15 months, 35 patients died of sudden cardiac death and 50 patients died of nonsudden cardiac death. Sudden cardiac death was associated with ejection fraction <40%, nonsustained ventricular tachycardia, creatine kinase >1,000 IU/L, and late potentials in >75% of analyzed Holter ECGs (abnormal LP75), but not with late potentials determined by only a short ECG period. According to multivariate analysis, the best independent significant predictor of sudden cardiac death was abnormal LP75 (P = 0.002, sensitivity 29%, specificity 96%, positive predictive value 40%, negative predictive value 97%). Nonsudden cardiac death was associated with ejection fraction <40% (P = 0.001).

Conclusions: Late potential analysis of digital Holter ECG is a powerful tool that can be used to determine postinfarction patients at risk for sudden cardiac death and is optimized when combined with determination of ejection fraction.
Termination of Reentry by a Long‐Lasting AC Shock in a Slice of Canine Heart: A Computational Study
Authors: MEUNIER JASON M. , EASON JAMES C. , TRAYANOVA NATALIA A.
Published: August 2003

AC Cardioversion in a Canine Slice.
Introduction: A heart in fibrillation can be entrained by long‐lasting alternating current (AC) stimuli, leading to defibrillation. To investigate the role entrainment plays in defibrillation, computer simulations of AC cardioversion in a three‐dimensional slice of the canine heart were performed.

Methods and Results: A bidomain finite element model of a 1‐mm thick slice across the ventricles of a canine heart was used to simulate termination of transmural reentry with AC shocks. Cardioversion defibrillation thresholds (DFTs) were determined for 200‐msec (L) AC shocks at varying frequencies. At the DFT, the entire tissue is entrained by the AC shock. DFT decreases as the frequency of the long‐lasting AC shock increases. We hypothesize that this decrease is due to the short period of the high‐frequency AC waveform, leaving strong virtual electrode polarization (VEP) after the shock ends. To test this hypothesis, the end‐shock VEP were compared for different frequencies, demonstrating stronger polarization as frequency increased. To examine whether entrainment by the long‐lasting AC shock contributes to the VEP at the end of the shock, additional simulations were conducted using single‐period (Z) AC waveforms. Z waveform DFTs were higher than L waveform DFTs; the Z waveform VEP was weaker than the L waveform VEP at the same frequency. This indicates that entrainment contributes to the development of stronger VEP and, thus, to lower DFT at high frequencies.

Conclusion: This study offers for the first time a mechanistic insight into cardioversion with long‐lasting AC shocks.
Unique targeting of cytosolic phospholipase A2 to plasma membranes mediated by the NADPH oxidase in phagocytes
Authors: Shmelzer Zeev , Haddad Nurit , Admon Ester , Pessach Itai , Leto Thomas L. , Eitan-Hazan Zahit , Hershfinkel Michal , Levy Rachel
Published: August 2003

Cytosolic phospholipase A2 (cPLA2)–generated arachidonic acid (AA) has been shown to be an essential requirement for the activation of NADPH oxidase, in addition to its being the major enzyme involved in the formation of eicosanoid at the nuclear membranes. The mechanism by which cPLA2 regulates NADPH oxidase activity is not known, particularly since the NADPH oxidase complex is localized in the plasma membranes of stimulated cells. The present study is the first to demonstrate that upon stimulation cPLA2 is transiently recruited to the plasma membranes by a functional NADPH oxidase in neutrophils and in granulocyte-like PLB-985 cells. Coimmunoprecipitation experiments and double labeling immunofluorescence analysis demonstrated the unique colocalization of cPLA2 and the NADPH oxidase in plasma membranes of stimulated cells, in correlation with the kinetic burst of superoxide production. A specific affinity in vitro binding was detected between GST-p47phox or GST-p67phox and cPLA2 in lysates of stimulated cells. The association between these two enzymes provides the molecular basis for AA released by cPLA2 to activate the assembled NADPH oxidase. The ability of cPLA2 to regulate two different functions in the same cells (superoxide generation and eicosanoid production) is achieved by a novel dual subcellular localization of cPLA2 to different targets.
Identification of PVR (CD155) and Nectin-2 (CD112) as Cell Surface Ligands for the Human DNAM-1 (CD226) Activating Molecule
Authors: Bottino Cristina , Castriconi Roberta , Pende Daniela , Rivera Paola , Nanni Marina , Carnemolla Barbara , Cantoni Claudia , Grassi Jessica , Marcenaro Stefania , Reymond Nicolas , Vitale Massimo , Moretta Lorenzo , Lopez Marc , Moretta Alessandro
Published: August 2003

Human natural killer (NK) cells express a series of activating receptors and coreceptors that are involved in recognition and killing of target cells. In this study, in an attempt to identify the cellular ligands for such triggering surface molecules, mice were immunized with NK-susceptible target cells. On the basis of a functional screening, four mAbs were selected that induced a partial down-regulation of the NK-mediated cytotoxicity against the immunizing target cells. As revealed by biochemical analysis, three of such mAbs recognized molecules of ∼70 kD. The other mAb reacted with two distinct molecules of ∼65 and 60 kD, respectively. Protein purification followed by tryptic digestion and mass spectra analysis, allowed the identification of the 70 kD and the 65/60 kD molecules as PVR (CD155) and Nectin-2 δ/α (CD112), respectively. PVR-Fc and Nectin-2-Fc soluble hybrid molecules brightly stained COS-7 cells transfected with the DNAM-1 (CD226) construct, thus providing direct evidence that both PVR and Nectin-2 represent specific ligands for the DNAM-1 triggering receptor. Finally, the surface expression of PVR or Nectin-2 in cell transfectants resulted in DNAM-1–dependent enhancement of NK-mediated lysis of these target cells. This lysis was inhibited or even virtually abrogated upon mAb-mediated masking of DNAM-1 (on NK cells) or PVR or Nectin-2 ligands (on cell transfectants).
State-dependent Block of Wild-type and Inactivation-deficient Na+ Channels by Flecainide
Authors: Wang Ging Kuo , Russell Corinna , Wang Sho-Ya
Published: August 2003

The antiarrhythmic agent flecainide appears beneficial for painful congenital myotonia and LQT-3/ΔKPQ syndrome. Both diseases manifest small but persistent late Na+ currents in skeletal or cardiac myocytes. Flecainide may therefore block late Na+ currents for its efficacy. To investigate this possibility, we characterized state-dependent block of flecainide in wild-type and inactivation-deficient rNav1.4 muscle Na+ channels (L435W/L437C/A438W) expressed with β1 subunits in Hek293t cells. The flecainide-resting block at −140 mV was weak for wild-type Na+ channels, with an estimated 50% inhibitory concentration (IC50) of 365 μM when the cell was not stimulated for 1,000 s. At 100 μM flecainide, brief monitoring pulses of +30 mV applied at frequencies as low as 1 per 60 s, however, produced an ∼70% use-dependent block of peak Na+ currents. Recovery from this use-dependent block followed an exponential function, with a time constant over 225 s at −140 mV. Inactivated wild-type Na+ channels interacted with flecainide also slowly at −50 mV, with a time constant of 7.9 s. In contrast, flecainide blocked the open state of inactivation-deficient Na+ channels potently as revealed by its rapid time-dependent block of late Na+ currents. The IC50 for flecainide open-channel block at +30 mV was 0.61 μM, right within the therapeutic plasma concentration range; on-rate and off-rate constants were 14.9 μM−1s−1 and 12.2 s−1, respectively. Upon repolarization to −140 mV, flecainide block of inactivation-deficient Na+ channels recovered, with a time constant of 11.2 s, which was ∼20-fold faster than that of wild-type counterparts. We conclude that flecainide directly blocks persistent late Na+ currents with a high affinity. The fast-inactivation gate, probably via its S6 docking site, may further stabilize the flecainide-receptor complex in wild-type Na+ channels.
The Retrieval Function of the KDEL Receptor Requires PKA Phosphorylation of Its C-Terminus
Authors: Cabrera Margarita , Muñiz Manuel , Hidalgo Josefina , Vega Lucia , Martín María Esther , Velasco Angel
Published: August 2003

The KDEL receptor is a Golgi/intermediate compartment-located integral membrane protein that carries out the retrieval of escaped ER proteins bearing a C-terminal KDEL sequence. This occurs throughout retrograde traffic mediated by COPI-coated transport carriers. The role of the C-terminal cytoplasmic domain of the KDEL receptor in this process has been investigated. Deletion of this domain did not affect receptor subcellular localization although cells expressing this truncated form of the receptor failed to retain KDEL ligands intracellularly. Permeabilized cells incubated with ATP and GTP exhibited tubular processes-mediated redistribution from the Golgi area to the ER of the wild-type receptor, whereas the truncated form lacking the C-terminal domain remained concentrated in the Golgi. As revealed with a peptide-binding assay, this domain did not interact with both coatomer and ARF-GAP unless serine 209 was mutated to aspartic acid. In contrast, alanine replacement of serine 209 inhibited coatomer/ARF-GAP recruitment, receptor redistribution into the ER, and intracellular retention of KDEL ligands. Serine 209 was phosphorylated by both cytosolic and recombinant protein kinase A (PKA) catalytic subunit. Inhibition of endogenous PKA activity with H89 blocked Golgi-ER transport of the native receptor but did not affect redistribution to the ER of a mutated form bearing aspartic acid at position 209. We conclude that PKA phosphorylation of serine 209 is required for the retrograde transport of the KDEL receptor from the Golgi complex to the ER from which the retrieval of proteins bearing the KDEL signal depends.
Structure and Properties of an Engineered Transketolase from Maize
Authors: Gerhardt Stefan , Echt Stefanie , Busch Marco , Freigang Jörg , Auerbach Günter , Bader Gerd , Martin William F. , Bacher Adelbert , Huber Robert , Fischer Markus
Published: August 2003

The gene specifying plastid transketolase (TK) of maize (Zea mays) was cloned from a cDNA library by southern blotting using a heterologous probe from sorghum (Sorghum bicolor). A recombinant fusion protein comprising thioredoxin of Escherichia coli and mature TK of maize was expressed at a high level in E. coli and cleaved with thrombin, affording plastid TK. The protein in complex with thiamine pyrophoshate was crystallized, and its structure was solved by molecular replacement. The enzyme is a C2 symmetric homodimer closely similar to the enzyme from yeast (Saccharomyces cerevisiae). Each subunit is folded into three domains. The two topologically equivalent active sites are located in the subunit interface region and resemble those of the yeast enzyme.
Aluminum-Induced Gene Expression and Protein Localization of a Cell Wall-Associated Receptor Kinase in Arabidopsis
Authors: Sivaguru Mayandi , Ezaki Bunichi , He Zheng-Hui , Tong Hongyun , Osawa Hiroki , Baluška František , Volkmann Dieter , Matsumoto Hideaki
Published: August 2003

Here, we report the aluminum (Al)-induced organ-specific expression of a WAK1 (cell wall-associated receptor kinase 1) gene and cell type-specific localization of WAK proteins in Arabidopsis. WAK1-specific reverse transcriptase-polymerase chain reaction analysis revealed an Al-induced WAK1 gene expression in roots. Short- and long-term analysis of gene expression in root fractions showed a typical “on” and “off” pattern with a first peak at 3 h of Al exposure followed by a sharp decline at 6 h and a complete disappearance after 9 h of Al exposure, suggesting the WAK1 is a further representative of Al-induced early genes. In shoots, upon root Al exposure, an increased but stable WAK1 expression was observed. Using confocal microscopy, we visualized Al-induced closure of leaf stomata, consistent with previous suggestions that the Al stress primarily experienced in roots associated with the transfer of root-shoot signals. Elevated levels of WAK protein in root cells were observed through western blots after 6 h of Al exposure, indicating a lag time between the Al-induced WAK transcription and translation. WAK proteins are localized abundantly to peripheries of cortex cells within the elongation zone of the root apex. In these root cells, disintegration of cortical microtubules was observed after Al treatment but not after the Al analog lanthanum treatments. Tip-growing control root hairs, stem stomata, and leaf stomatal pores are characterized with high amounts of WAKs, suggesting WAKs are accumulating at plasma membrane domains, which suffer from mechanical stress and lack dense arrays of supporting cortical microtubules. Further, transgenic plants overexpressing WAK1 showed an enhanced Al tolerance in terms of root growth when compared with the wild-type plants, making the WAK1 one of the important candidates for plant defense against Al toxicity.
Interallelic Complementation at the Ubiquitous Urease Coding Locus of Soybean
Authors: Goldraij Ariel , Beamer Lesa J. , Polacco Joe C.
Published: August 2003

Soybean (Glycine max [L.] Merrill) mutant aj6 carries a single recessive lesion, aj6, that eliminates ubiquitous urease activity in leaves and callus while retaining normal embryo-specific urease activity. Consistently, aj6/aj6 plants accumulated urea in leaves. In crosses of aj6/aj6 by urease mutants at the Eu1, Eu2, and Eu3 loci, F1 individuals exhibited wild-type leaf urease activity, and the F2 segregated urease-negative individuals, demonstrating that aj6 is not an allele at these loci. F2 of aj6/aj6 crossed with a null mutant lacking the Eu1-encoded embryo-specific urease showed that ubiquitous urease was also inactive in seeds of aj6/aj6. The cross of aj6/aj6 to eu4/eu4, a mutant previously assigned to the ubiquitous urease structural gene (R.S. Torisky, J.D. Griffin, R.L. Yenofsky, J.C. Polacco [1994] Mol Gen Genet 242: 404–414), yielded an F1 having 22% ± 11% of wild-type leaf urease activity. Coding sequences for ubiquitous urease were cloned by reverse transcriptase-polymerase chain reaction from wild-type, aj6/aj6, and eu4/eu4 leaf RNA. The ubiquitous urease had an 837-amino acid open reading frame (ORF), 87% identical to the embryo-specific urease. The aj6/aj6 ORF showed an R201C change that cosegregated with the lack of leaf urease activity in a cross against a urease-positive line, whereas the eu4/eu4 ORF showed a G468E change. Heteroallelic interaction in F2 progeny of aj6/aj6 × eu4/eu4 resulted in partially restored leaf urease activity. These results confirm that aj6/aj6 and eu4/eu4 are mutants affected in the ubiquitous urease structural gene. They also indicate that radical amino acid changes in distinct domains can be partially compensated in the urease heterotrimer.
Regulated Phosphorylation of 40S Ribosomal Protein S6 in Root Tips of Maize
Authors: Williams Alan J. , Werner-Fraczek Joanna , Chang Ing-Feng , Bailey-Serres Julia
Published: August 2003

Ribosomal protein S6 (RPS6) is located in the mRNA binding site of the 40S subunit of cytosolic ribosomes. Two maize (Zea mays) rps6 genes were identified that encode polypeptides (30 kD, 11.4 pI) with strong primary amino acid sequence and predicted secondary structure similarity to RPS6 of other eukaryotes. Maize RPS6 was analyzed by the use of two-dimensional gel electrophoresis systems, in vivo labeling with [32P]Pi and immunological detection. Nine RPS6 isoforms were resolved in a two-dimensional basic-urea/sodium dodecyl sulfate-polyacrylamide gel electrophoresis system. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry performed on trypsin-digested isoforms identified four serine (Ser) and one threonine (Thr) residue in the carboxy-terminal region as phosphorylation sites (RRS238KLS241AAAKAS247AAT250S251A-COOH). Heterogeneity in RPS6 phosphorylation was a consequence of the presence of zero to five phosphorylated residues. Phosphorylated isoforms fell into two groups characterized by (a) sequential phosphorylation of Ser-238 and Ser-241 and (b) the absence of phospho-Ser-238 and presence of phospho-Ser-241. The accumulation of hyper-phosphorylated isoforms with phospho-Ser-238 was reduced in response to oxygen deprivation and heat shock, whereas accumulation of these isoforms was elevated by cold stress. Salt and osmotic stress had no reproducible effect on RPS6 phosphorylation. The reduction in hyper-phosphorylated isoforms under oxygen deprivation was blocked by okadaic acid, a Ser/Thr phosphatase inhibitor. By contrast, the recovery of hyper-phosphorylated isoforms upon re-oxygenation was blocked by LY-294002, an inhibitor of phosphatidylinositol 3-kinases. Thus, differential activity of phosphatase(s) and kinase(s) determine complex heterogeneity in RPS6 phosphorylation.
An Anaplerotic Role for Mitochondrial Carbonic Anhydrase in Chlamydomonas reinhardtii
Authors: Giordano Mario , Norici Alessandra , Forssen Magnus , Eriksson Mats , Raven John A.
Published: August 2003

Previous studies of the mitochondrial carbonic anhydrase (mtCA) of Chlamydomonas reinhardtii showed that expression of the two genes encoding this enzyme activity required photosynthetically active radiation and a low CO2 concentration. These studies suggested that the mtCA was involved in the inorganic carbon-concentrating mechanism. We have now shown that the expression of the mtCA at low CO2 concentrations decreases when the external NH4  + concentration decreases, to the point of being undetectable when NH4  + supply restricts the rate of photoautotrophic growth. The expression of mtCA can also be induced at supra-atmospheric partial pressure of CO2 by increasing the NH4  + concentration in the growth medium. Conditions that favor mtCA expression usually also stimulate anaplerosis. We therefore propose that the mtCA is involved in supplying HCO3  - for anaplerotic assimilation catalyzed by phosphoenolpyruvate carboxylase, which provides C skeletons for N assimilation under some circumstances.
Jung, Evans‐Wentz and various other gurus
Authors: McGuire William
Published: August 2003

How did Jung become deeply concerned with Asian religions and particularly with the Tibetan Buddhism of a Welshman from Trenton, New Jersey? Could that man be considered one of Jung's gurus? This essay begins six years after Jung, at twenty, was admitted to the medical school of Basel University and became a member of the Zofingiaverein, a student society. The next year he gave the first of a series of lectures on the interpretation of Christ as the model of the ‘god‐man’, like the Apostle Paul, Confucius, Zoroaster and the Buddha, who was ‘drummed into the Hindu boy’. (Jung's Zofingia Lectures were discovered only after his death, in 1961, and were published in English in 1983). The present essay discusses Jung's early Buddhist interest as displayed in The Psychology of the Unconscious (finally, in a revision, entitled Symbols of Transformation), in Psychological Types and later in his foreword of the Wilhelm translation of the I Ching. Jung was influenced by the gurus Richard Wilhelm and his son Hellmut, the scholar J. W. Hauer (with whom he later broke off relations because of Hauer's Nazi politics), the indologist Heinrich Zimmer, and the Zen master D. T. Suzuki. Walter Yeeling Wentz was born in Trenton in 1878 and brought up in his family's theosophist faith. The Wentzes moved to San Diego in 1900, and Walter added his mother's Celtic surname, Evans, to the German Wentz. He was educated at Stanford University and travelled in Europe, studying Celtic folklore, and widely in the Near East, Tibet, India, and Oxford – studying religions everywhere and editing Tibetan books. He lived his last decades in San Diego and conducted a correspondence with Jung, while living in a cheap hotel, or in an ashram.
Trauma and daimonic reality in Ferenczi's later work
Authors: Kalsched Donald
Published: August 2003

Jung and Ferenczi made independent discoveries of an ‘archaic’ (Jung) or ‘primordial’ (Ferenczi) layer of the psyche that shone through the ‘basic fault’ in the psyche opened by childhood trauma. This paper explores those parallels through an extended vignette of Ferenczi's work with Elizabeth Severn, known as ‘R. N.’ in the Clinical Diary. A remarkable inner object known as ‘Orpha’ appeared in the patient's trauma experience and saved a seed of personality from total annihilation. Ferenczi's speculation about this ‘daimonic’ object is cited along with his discussion of a trans‐personal immaterial reality that Orpha makes visible, and that links the patient's ego‐experience with a spiritual/material unity not ordinarily available to consciousness.
Toni Wolff–James Kirsch correspondence
Authors: Kirsch Thomas B.
Published: August 2003

This paper draws on the letters between Toni Wolff and James Kirsch from 1929–1933 and from 1949–1953 to highlight some aspects of Toni Wolff's relationship with her supervisee and former analysand, James Kirsch. Her personality, her approach to her work as analyst, and her relationship with Jung and with colleagues are illustrated with selected quotes from the correspondence.
Joseph Henderson  A tribute
Authors: Stein Murray , Beebe John
Published: August 2003

Joseph Henderson has been on the Editorial Board of the Journal of Analytical Psychology since its inception in 1955. He will be 100 years old this year and this, with the bibliography of his publications over the past quarter century that follows, is the Journal's tribute to him for all his contributions.
Efficiency and TFP Growth in the Spanish Regions: The Role of Human and Public Capital
Authors: Jiménez Maria del Mar Salinas
Published: August 2003

Abstract This paper analyzes the productivity growth of the Spanish regions between 1965 and 1995, decomposing productivity gains into technological progress and efficiency change by means of Malmquist indices. Once estimates of efficiency are obtained, the aim of this paper is to analyze the effects of human and public capital on growth in terms of their impact on Total Factor Productivity (TFP). Public capital is believed to increase the productivity of the private factors of production whereas human capital is thought to contribute to the production process as an additional input and to have a dynamic influence on growth through its impact on technological innovation (shifts in the production frontier) and technological diffusion (movements toward the frontier), which are the components of this TFP measure. Considering inefficiencies will then allow the effects of these variables on TFP growth to be estimated via technological progress and efficiency gains.
Financing Choice and Liability Structure of Real Estate Investment Trusts
Authors: Brown David T. , Riddiough Timothy J.
Published: August 2003

We conduct an analysis of public financial offerings of equity Real Estate Investment Trusts (REITs), with a focus on liability structure effects and whether or not firms target longer‐run debt ratios. Our major findings are that (1) proceeds from equity offers are more likely to fund investment, whereas public debt offer proceeds are typically used to reconfigure the liability structure of the firm; (2) public debt issuers are often capital constrained and target total leverage ratios to retain an investment grade credit rating; and (3) the preoffer liability structure affects the issuance choice decision, in that firms with higher preoffer levels of secured (unsecured) debt tend to issue equity (public debt). Other notable findings are that the market for public REIT debt is integrated with the broader debt markets and that higher credit quality firms issue longer‐maturing bonds.
Dividend Pricing Models and REITs
Authors: Kallberg Jarl G. , Liu Crocker H. , Srinivasan Anand
Published: August 2003

Dividend pricing/present value models relate current stock prices to expectations of future dividends. In this study we apply the West and Campbell–Shiller tests of the dividend pricing relation to an index of real estate investment trusts (REITs). REITs provide a unique test of these models since, during our study period, REITs were mandated to pay out at least 95% of taxable income as dividends. While our results complement previous research which finds that the dividend pricing model cannot be rejected if share repurchase is included as part of dividends, our data contain a much less significant amount of share repurchase, so that our approach to the issue of the viability of dividend pricing models offers an alternative insight. Our research suggests that, for our REIT population, dividend pricing models cannot be rejected.