bluuebunny/crossref_metadata_2025 huggingface dataset:
Mediators of coronary reactive hyperaemia in isolated mouse heart
Authors: Zatta Amanda J , Headrick John P
Published: January 2005

Mechanisms regulating coronary tone under basal conditions and during reactive hyperaemia following transient ischaemia were assessed in isolated mouse hearts.

Blockade of NO‐synthase (50 μM L‐NAME), KATP channels (5 μM glibenclamide), A2A adenosine receptors (A2AARs; 100 nM SCH58261), prostanoid synthesis (100 μM indomethacin), and EDHF (100 nM apamin+100 nM charybdotoxin) all reduced basal flow ∼40%. Effects of L‐NAME, glibenclamide, and apamin+charybdotoxin were additive, whereas coadministration of SCH58261 and indomethacin with these inhibitors failed to further limit flow.

Substantial hyperaemia was observed after 5–40 s occlusions, with flow increasing to a peak of 48±1 ml min−1 g−1. Glibenclamide most effectively inhibited peak flows (up to 50%) while L‐NAME was ineffective.

With longer occlusions (20–40 s), glibenclamide alone was increasingly ineffective, reducing peak flows by ∼15% after 20 s occlusion, and not altering peak flow after 40 s occlusion. However, cotreatment with L‐NAME+glibenclamide inhibited peak hyperaemia by 70 and 25% following 20 and 40 s occlusions, respectively.

In contrast to peak flow changes, sustained dilation and flow repayment over 60 s was almost entirely KATP channel and NO dependent (each contributing equally) with all occlusion durations.

Antagonism of A2AARs with SCH58261 reduced hyperaemia 20–30% whereas inhibition of prostanoid synthesis was ineffective. Effects of A2AAR antagonism were absent in hearts treated with L‐NAME and glibenclamide, supporting NO and KATP‐channel‐dependent effects of A2AARs.

EDHF inhibition alone exerted minor effects on hyperaemia and only with longer occlusions. However, residual hyperaemia after 40 s occlusion in hearts treated with L‐NAME+glibenclamide+SCH58261+indomethacin was abrogated by cotreatment with apamin+charybdotoxin.

Data support a primary role for KATP channels and NO in mediating sustained dilation after coronary occlusion. While KATP channels (and not NO) are also important in mediating initial peak flow adjustments after brief 5–10 s occlusions, their contribution declines with longer 20–40 s occlusions. Intrinsic activation of A2AARs is important in triggering KATP channel/NO‐dependent hyperaemia. Synergistic effects of combined inhibitors implicate interplay between mediators, with compensatory changes occurring in KATP channel, NO, and/or EDHF responses when one is individually blocked.

British Journal of Pharmacology (2005) 144, 576–587. doi:10.1038/sj.bjp.0706099
Nitric oxide relaxes circular smooth muscle of rat distal colon through RhoA/Rho‐kinase independent Ca2+ desensitisation
Authors: Colpaert Erwin E , Levent Adnan , Lefebvre Romain A
Published: January 2005

The aim of this study in circular smooth muscle of rat distal colon was to determine whether Ca2+ desensitisation, in addition to mechanisms lowering cytosolic free Ca2+ concentration ([Ca2+]cyt), was involved in the relaxation elicited by nitric oxide (NO). Changes in isometric tension and [Ca2+]cyt were recorded simultaneously in fura‐2‐loaded strips.

In methacholine (10−5 M)‐precontracted preparations, exogenous NO (10−4 M), adenosine 5′‐triphosphate (ATP; 10−3 M) and electrical field stimulation (EFS; 1 ms, 40 V, 4 Hz, 1 min) induced a decrease in smooth muscle tension, which was accompanied by a fall in [Ca2+]cyt.

The sarcoplasmic/endoplasmic reticulum Ca2+ ATP‐ase (SERCA) inhibitor thapsigargin (10−6 M) did not exert an influence on the decrease in tension produced by exogenous NO, but significantly attenuated the fall in [Ca2+]cyt. Both the relaxation and the fall in [Ca2+]cyt to ATP and EFS were unaffected by thapsigargin.

Calyculin‐A (10−6 M), a myosin light chain phosphatase (MLCP) inhibitor, significantly reduced the decrease in tension elicited by exogenous NO, but did not alter the fall in [Ca2+]cyt to exogenous NO. Inactivating RhoA by exoenzyme C3 (2 μg ml−1) or inhibiting Rho‐kinase with (+)‐(R)‐trans‐4‐(1‐aminoethyl)‐N‐(4‐pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y‐27632; 10−5 M) had no effect on the decrease of both tension and [Ca2+]cyt generated by exogenous NO.

This paper demonstrates that a RhoA/Rho‐kinase independent Ca2+ desensitisation pathway contributes to the relaxation by NO in circular smooth muscle strips of rat distal colon.

British Journal of Pharmacology (2005) 144, 588–594. doi:10.1038/sj.bjp.0706111
The role of membranes and membrane trafficking in RNA localization
Authors: Cohen Robert S.
Published: January 2005

Eukaryotic cells possess highly sophisticated membrane trafficking pathways that define specific membrane domains and provide a means for moving vesicles between them (Mostov, Su, and ter Beest, 2003, Nat. Cell Biol. 5, 287–293). Here, I review recent data that indicate a role for membrane trafficking in mRNA localization. Specifically, I review evidence that some localized mRNAs are anchored to specific membrane domains and/or transported on membranous organelles or vesicles to specific subcellular sites. This review is not intended as a discussion on indirect influences of membrane trafficking on mRNA localization. I will not, for example, discuss the role of membrane trafficking in the regulation of extracellular signalling events that could indirectly influence mRNA localization through polarization of the actin or microtubule cytoskeleton (for examples, see reviews by Drubin and Nelson, 1996, Cell 84, 335–344; Shulman and St Johnston, 1999, Trends Cell Biol. 9, M60–M64).
How and why does β‐actin mRNA target?
Authors: Condeelis John , Singer Robert H.
Published: January 2005

β‐Actin mRNA is localized near the leading edge in several cell types where actin polymerization is actively promoting forward protrusion. The localization of the β‐actin mRNA near the leading edge is facilitated by a short sequence in the 3′UTR (untranslated region), the ‘zipcode’. Localization of the mRNA at this region is important physiologically. Treatment of chicken embryo fibroblasts with antisense oligonucleotides complementary to the localization sequence (zipcode) in the 3′UTR leads to delocalization of β‐actin mRNA, alteration of cell phenotype and a decrease in cell motility. The dynamic image analysis system (DIAS) used to quantify movement of cells in the presence of sense and antisense oligonucleotides to the zipcode showed that net pathlength and average speed of antisense‐treated cells were significantly lower than in sense‐treated cells. This suggests that a decrease in persistence of direction of movement and not in velocity results from treatment of cells with zipcode‐directed antisense oligonucleotides. We postulate that delocalization of β‐actin mRNA results in delocalization of nucleation sites and β‐actin protein from the leading edge followed by loss of cell polarity and directional movement. Hence the physiological consequences of β‐actin mRNA delocalization affect the stability of the cell phenotype.
Drosophila neural progenitor polarity and asymmetric division
Authors: Wang Hongyan , Chia William
Published: January 2005

In the Drosophila embryonic central nervous system, the neural precursor cells called neuroblasts undergo a number of asymmetric divisions along the apical—basal axis to give rise to different daughter cells of distinct fates. This review summarizes recent progress in understanding the mechanisms of these asymmetric cell divisions. We discuss proteins that are localized at distinct domains of cortex in the neuroblasts and their role in generating asymmetry. We also review uniformly cortical localized factors and actin cytoskeleton‐associated motor proteins with regard to their potential role to serve as a link between distinct cortical domains in the neuroblasts. In this review, asymmetric divisions of sensory organ precursor and larval neuroblasts are also briefly discussed.
RNA localization in yeast: moving towards a mechanism
Authors: Gonsalvez Graydon B. , Urbinati Carl R. , Long Roy M.
Published: January 2005

RNA localization is a widely utilized strategy employed by cells to spatially restrict protein function. In Saccharomyces cerevisiae asymmetric sorting of mRNA to the bud has been reported for at least 24 mRNAs. The mechanism by which the mRNAs are trafficked to the bud, illustrated by ASH1 mRNA, involves recognition of cis‐acting localization elements present in the mRNA by the RNA‐binding protein, She2p. The She2p/mRNA complex subsequently associates with the myosin motor protein, Myo4p, through an adapter, She3p. This ribonucleoprotein complex is transported to the distal tip of the bud along polarized actin cables. While the mechanism by which ASH1 mRNA is anchored at the bud tip is unknown, current data point to a role for translation in this process, and the rate of translation of Ash1p during the transport phase is regulated by the cis‐acting localization elements. Subcellular sorting of mRNA in yeast is not limited to the bud; certain mRNAs corresponding to nuclear‐encoded mitochondrial proteins are specifically sorted to the proximity of mitochondria. Analogous to ASH1 mRNA localization, mitochondrial sorting requires cis‐acting elements present in the mRNA, though trans‐acting factors involved with this process remain to be identified. This review aims to discuss mechanistic details of mRNA localization in S. cerevisiae.
Putting RNAs in the right place at the right time: RNA localization in the frog oocyte
Authors: King Mary Lou , Messitt Timothy J. , Mowry Kimberly L.
Published: January 2005

Localization of maternal mRNAs in many developing organisms provides the basis for both initial polarity during oogenesis and patterning during embryogenesis. Prominent examples of this phenomenon are found in Xenopus laevis, where localized maternal mRNAs generate developmental polarity along the animal/vegetal axis. Targeting of mRNA molecules to specific subcellular regions is a fundamental mechanism for spatial regulation of gene expression, and considerable progress has been made in defining the underlying molecular pathways.
Maternal determinants and mRNAs in the cortex of ascidian oocytes, zygotes and embryos
Authors: Sardet Christian , Dru Philippe , Prodon François
Published: January 2005

The peripheral region of ascidian oocytes and zygotes contains five determinants for morphogenesis and differentiation of the embryo. The determinant for the 24 primary muscle cells of the tadpole, macho1, is one of several cortical mRNAs localized in a gradient along the animal—vegetal axis in the oocyte. After fertilization these mRNAs, together with cortical endoplasmic reticulum (cER) and a subcortical mitochondria‐rich domain (myoplasm), relocate in two major reorganization phases forming the posterior plasm (postplasm) of the zygote. At the 8‐cell stage cortical mRNAs concentrate in a macroscopic cortical structure called the centrosome‐attracting body (CAB), forming a characteristic posterior end mark (PEM) in the two posterior vegetal blastomeres. We propose to call the numerous mRNAs showing this particular cortical localization in the posterior region of the embryo postplasmic/PEM RNAs and suggest a nomemclature. We do not know how postplasmic/PEM RNAs reach their polarized distribution in the oocyte cortex but at least PEM1 and macho1 (and probably others) bind to the network of cER retained in isolated cortical fragments. We propose that after fertilization, these postplasmic/PEM mRNAs move in the zygote cortex together with the cER network (cER/mRNA domain) via microfilament‐ and microtubule‐driven translocations. The cER/mRNA domain is localized posteriorly at the time of first cleavage and distributed equally between the first two blastomeres. After the third cleavage, the cER/mRNA domain and dense particles compact to form the CAB in posterior vegetal blastomeres of the 8‐cell stage. We discuss the identity of postplasmic/PEM RNAs, how they localize, anchor, relocate and may be translated. We also examine their roles in unequal cleavage and as a source of posterior morphogenetic and differentiation factors.
VICKZ proteins: a multi‐talented family of regulatory RNA‐binding proteins
Authors: Yisraeli Joel K.
Published: January 2005

The highly conserved VICKZ (Vg1 RBP/Vera, IMP‐1,2,3, CRD‐BP, KOC, ZBP‐1) family of RNA‐binding proteins recognize specific cis‐acting elements in a variety of different RNAs and have been implicated in cell polarity and migration, cell proliferation, and cancer. In just the last two years, the use of transgenic mice, antisense RNA, and RNAi (RNA interference) techniques have contributed to our understanding of the roles of these proteins and how they interface with many diverse processes in cells. In this article, I will review the recent advances relating to VICKZ proteins and try to suggest a framework for understanding how, in conjunction with other RNA‐binding proteins, they participate in a combinatorial fashion to help determine the fate of their RNA targets and, ultimately, the function of cells in which they are expressed. Such a ‘post‐transcriptional operon’ model, as proposed by Keene and Tenenbaum [(2002) Mol. Cell 9, 1161‐1167], can explain the differential, integrated action of multiple RNA‐binding proteins on mRNA targets.
Atrioventricular Junction Ablation and Pacemaker Therapy in Patients with Drug‐Resistant Atrial Tachyarrhythmias after the Fontan Operation
Authors: FRIEDMAN RICHARD A. , WILL JOACHIM C. , FENRICH ARNOLD L. , KERTESZ NAOMI J.
Published: January 2005

Introduction: Drug‐resistant intraatrial reentrant tachycardia (IART) occurs frequently after the Fontan operation and is a major cause of morbidity and rarely mortality. We describe our experience with AV junction ablation after pacemaker implantation in postoperative Fontan patients with drug‐resistant IART.

Methods and Results: We performed retrospective analysis of Fontan patients with IART and attempted radiofrequency ablation (RFA) of the AV junction. Seven patients (6 male) were identified, with a mean age at Fontan of 9.3 years (range 5.8–13.3) and a median age at RFA of 18 years (range 14.5–23.3). Mean follow‐up prior to RFA was 764 ± 235 days and after RFA 1,541 ± 1,235 days. IART was refractory to antiarrhythmic drugs in all patients, and all had undergone pacemaker placement. Mean onset of IART was 44.1 months (range 0–142) after Fontan. Mean duration of atrial arrhythmia prior to RFA was 72 ± 48 m (range 16–148). Ablation of the AV junction was successful or partially successful in all patients. Complete AV block occurred in 6 patients. Normal AV conduction was not seen during a mean follow‐up of 1,541 days. The mean number of antiarrhythmic medications decreased from 2.8 ± 1.5 to 0.7 ± 0.8 (P < 0.05).

Conclusion: In Fontan patients with drug‐resistant IART, RFA of the AV junction with prior pacemaker implant is an effective therapeutic option. Despite the introduction of pacemaker dependence, this option should be considered in patients who did not respond to RFA of IART or who are at high operative risk for Fontan conversion.
QT Correction Methods in Children and Adolescents
Authors: WERNICKE JOACHIM F. , FARIES DOUGLAS , BREITUNG REBECCA , GIROD DONALD
Published: January 2005

Introduction: Accurate determination of the QTc interval has become increasingly important in the assessment of a drug's ability to prolong cardiac repolarization. Previous work suggests the most appropriate correction formula for adults is QTc = QT/RR0.40, but little on correction methods for children and adolescents has been published.

Methods and Results: In this study, ECG data were obtained from a meta‐analysis of seven clinical trials for attention deficit/hyperactivity disorder (ADHD) involving 2,288 children and adolescents. The most appropriate formula for children and adolescents included in this database was found to be QTc = QT/RR0.38. Adjustments of the correction factor specifically for males and females of different ages also are reported.

Conclusion: QT correction methods developed for adults do not apply to children. As accurate QTc determination plays a larger role in assessing a drug's potential to retard repolarization, use of age‐ and gender‐specific correction formulas becomes more important.
Hypertension and Hypertensive Heart Disease Are Associated with Increased Ostial Pulmonary Vein Diameter
Authors: HERWEG BENGT , SICHROVSKY TINA , POLOSAJIAN LEO , ROZENSHTEIN ANNA , STEINBERG JONATHAN S.
Published: January 2005

Introduction: Atrial fibrillation (AF) is associated with increased ostial pulmonary vein (PV) diameter and commonly with hypertension. We sought to investigate ostial PV anatomy in patients with and without AF with the goal of characterizing the relationship to hypertension and cardiovascular disease.

Methods and Results: Ostial PV diameter was assessed by preprocedural spiral computed tomography in 100 AF patients undergoing a PV isolation procedure and in 24 age‐ and sex‐matched non‐AF control patients. Ostial diameter of 392 PVs in 100 AF patients was increased compared to 106 PVs in 24 non‐AF controls (1.50 ± 0.31 vs 1.20 ± 0.31 cm, P < 0.001) and diameters of individual PVs were uniformly affected (r = 0.45–0.62, P < 0.001). Left atrial dilation was associated with a larger PV diameter (1.56 ± 0.32 vs 1.44 ± 0.29 cm, P < 0.01). PV diameter in AF patients with hypertension (1.55 ± 0.32 cm), particularly if associated with left ventricular hypertrophy (1.66 ± 0.37 cm), was larger compared to AF patients without hypertension (1.43 ± 0.26 cm, P < 0.01). PV diameter in control patients with hypertension (n = 14) was larger than in those without hypertension (n = 10, P < 0.01). Patients with persistent AF had larger PV diameters (1.61 ± 0.34 cm) than patients with paroxysmal AF (1.47 ± 0.30 cm, P < 0.01). Male gender (P < 0.01), history of hypertension (P < 0.01), and persistent AF (P < 0.05) were identified as independent cofactors of increased ostial PV diameter.

Conclusion: PV dilation affects all PVs uniformly in AF patients. Hypertension and hypertensive heart disease in patients with and without AF are associated with PV dilation, supporting theories that impaired left ventricular diastolic function is associated with a stretch‐induced PV arrhythmia mechanism.
Assessment of Markers for Identifying Patients at Risk for Life‐Threatening Arrhythmic Events in Brugada Syndrome
Authors: AJIRO YOUICHI , HAGIWARA NOBUHISA , KASANUKI HIROSHI
Published: January 2005

Introduction: Risk stratification for life‐threatening arrhythmic events in Brugada syndrome is not yet established. The aim of the present study was to examine the usefulness of various markers in predicting life‐threatening arrhythmic events in the Brugada syndrome.

Methods and Results: Forty‐six patients with Brugada‐type ECGs were categorized into the symptomatic (n = 28) and asymptomatic (n = 18) groups. Statistical analyses were performed with respect to the usefulness of the following markers: SCN5A mutation, pharmacologic challenge, ventricular fibrillation (VF) inducibility by programmed electrical stimulation, and late potential (LP) by signal‐averaged ECG (SAECG). Comparison between the two groups revealed a significant difference only in LP positivity (92.6% vs 47.1%, P = 0.0004). The symptomatic group had significantly lower RMS40, longer LAS40, and longer fQRSd compared with the asymptomatic group. A significant difference was noted, especially RMS40. The positive predictive value, negative predictive value, and predictive accuracy when setting a cutoff value of 15 μV were 92.0%, 78.9%, and 86.4%, respectively. Furthermore, patients with an RMS40 value <15 μV (n = 25) showed significantly higher rates of VF recurrence compared with patients with an RMS40 value ≥ 15 μV (n = 19, P = 0.047).

Conclusion: Regarding risk stratification for identifying high‐risk patients in Brugada syndrome, only LP by SAECG was shown to be useful, suggesting the importance of RMS40 in predicting the history of life‐threatening arrhythmic events and the recurrence of VF.
Absence of Msx2 Does Not Affect Cardiac Conduction or Rescue Conduction Defects Associated with Nkx2‐5 Mutation
Authors: JAY PATRICK Y. , MAGUIRE COLIN T. , WAKIMOTO HIROKO , IZUMO SEIGO , BERUL CHARLES I.
Published: January 2005

Introduction: The transcription factors governing embryonic development of the AV conduction system are largely unknown. Heterozygous mutations of the cardiac transcription factor Nkx2‐5 cause AV conduction defects, which are associated with anatomic hypoplasia of the conduction system. In situ expression patterns of Msx2 in the mouse and chick embryonic heart have suggested a developmental function for this transcription factor. Homozygous Nkx2‐5 knockout mouse embryos express Msx2 ectopically throughout the myocardium, suggesting Msx2 affects conduction system development through a transcriptional cascade starting with Nkx2‐5. Several observations support a model in which Msx2 negatively regulates formation of the conduction system and inappropriate Msx2 up‐regulation causes the conduction defects associated with Nkx2‐5 mutation.

Methods and Results: We obtained surface ECGs and performed intracardiac electrophysiologic studies in Msx2 knockout mice and in Nkx2‐5 wild‐type and heterozygous null mutant mice in an Msx2 null mutant background. Msx2 null mutant mice had normal cardiac conduction and no increased vulnerability to inducible arrhythmia. Absence of Msx2 did not alter the conduction defects observed in heterozygous Nkx2‐5 knockout mice.

Conclusion: Msx2 likely does not contribute to development of the conduction system. Abnormal Msx2 expression likely does not cause the AV conduction defects present in Nkx2‐5 knockout mice.
Morphologic Remodeling of Pulmonary Veins and Left Atrium after Catheter Ablation of Atrial Fibrillation:
Authors: TSAO HSUAN‐MING , WU MEI‐HAN , HUANG BIEN‐HSIEN , LEE SHIH‐HUANG , LEE KUN‐TAI , TAI CHING‐TAI , LIN YUNG‐KUO , HSIEH MING‐HSIUNG , KUO JEN‐YUAN , LEI MENG‐HUAN , CHEN SHIH‐ANN
Published: January 2005

Introduction: Understanding the structural remodeling and reverse remodeling of the left atrium (LA) and pulmonary vein (PV) after radiofrequency ablation of atrial fibrillation (AF) may provide important insights into the mechanism and management of AF. This study used magnetic resonance angiographic (MRA) images to investigate changes in PV and LA morphologies before and more than 1 year after ablation.

Method and Results: Forty‐five patients (36 men and 9 women, mean age 60 ± 13 years) who underwent MRA before and more than 12 months (mean 21 ± 11) after ablation of paroxysmal AF were included in the study. The patients were divided into two groups: group I included 35 patients without AF recurrence, and group II included 10 patients with late (>1 month postablation) recurrence of AF. The sizes of the LA and nonablated PV were compared before and after ablation. In group I, significant reduction of ostial area of both superior PVs was noted (left superior PV: from 2.85 ± 0.67 to 2.59 ± 0.73 cm2; right superior PV: from 2.89 ± 0.85 to 2.60 ± 0.73 cm2, both P < 0.001). Geometric alteration toward a round shape was noted in the ostia of superior PVs during follow‐up (eccentricity of right superior PV and left superior PV decreased from 0.31 ± 0.10 to 0.22 ± 0.13 and from 0.27 ± 0.11 to 0.19 ± 0.13, respectively, oth P < 0.01). However, LA volume showed only borderline reduction (from 61.52 ± 19.06 to 56.64 ± 17.13 mL, P = 0.05). In group II, significant dilation of the LA (from 61.14 ± 17.54 to 78.73 ± 25.27 mL, P = 0.004) and right superior PV (from 3.41 ± 1.12 to 4.08 ± 1.31 cm2, P = 0.016) was noted during follow‐up. Ostial area and eccentricity of the left superior, left inferior, and right inferior PVs and LA were similar before and after ablation.

Conclusion: Structural remodeling of the superior PVs and LA can be reversible after successful ablation without AF recurrence; however, late recurrence of AF is associated with progressive LA dilation.
Impaired Baroreflex Gain in Patients with Inappropriate Sinus Tachycardia
Authors: LEON HERNANDO , GUZMAN JUAN CAMILO , KUUSELA TOM , DILLENBURG REJANE , KAMATH MARK , MORILLO CARLOS A.
Published: January 2005

Introduction: The aim of this study was to determine the characteristics of heart rate variability (HRV), blood pressure variability (BPV), and baroreflex gain (BRG) at rest and during orthostatic stress in patients with clinical criteria of inappropriate sinus tachycardia (IST).

Methods and Results: Beat‐to‐beat HRV and BPV, measured by time‐ and frequency‐domain methods, and noninvasive BRG, calculated by cross‐spectral analysis, were obtained during 10 minutes both at rest and during the stabilization phase (5–15 min) of orthostatic stress at 60° in 8 patients with clinical criteria of IST and 9 healthy volunteers (CON). IST patients had a higher resting mean heart rate (78.8 ± 5.3 vs 58.5 ± 4.2 beats/min, P = 0.01) and mean blood pressure (90.4 ± 2.4 vs 72.0 ± 4.2 mmHg; P = 0.002). RMSSD, pNN50m, and BRG were significantly reduced in IST patients at rest. BRG during orthostatic stress (7.2 ± 0.8 vs 20.3 (2.4 ms/mmHg, P < 0.01) was significantly reduced in IST patients. Δ BRG (−16.9%± 11 vs −50.1%± 5, P = 0.02) was markedly blunted during orthostatic stress in IST patients.

Conclusion: BRG was markedly impaired both at rest and during orthostatic stress in IST patients. This alteration may be responsible for the higher resting heart rate and mean blood pressures seen at rest and may facilitate tachycardia during orthostatic stress. A primary alteration in sinus node automaticity coupled with impaired BRG determines heart rate response to orthostatic stress in patients with IST.
Further Insights into the Effect of Quinidine in Short QT Syndrome Caused by a Mutation in HERG
Authors: WOLPERT CHRISTIAN , SCHIMPF RAINER , GIUSTETTO CARLA , ANTZELEVITCH CHARLES , CORDEIRO JONATHAN , DUMAINE ROBERT , BRUGADA RAMON , HONG KUI , BAUERSFELD URS , GAITA FIORENZO , BORGGREFE MARTIN
Published: January 2005

Introduction: The principal aim of this study was to assess the efficacy of quinidine in suppressing IKr in vitro and in modulating the rate dependence of the QT interval in the “SQT1” form of the short QT syndrome.

Methods and Results: Graded‐intensity bicycle exercise testing was performed off drug in three patients and during oral quinidine in two patients with short QT syndrome and compared to a control group of healthy normal subjects. The in vitro effects of quinidine on currents in patch clamp technique were investigated. Off drugs QTpV3/heart rate correlation is much weaker in patients with short QT syndrome, and QTpV3 shortens less with heart rate increase compared to normal subjects. In addition to prolonging the QT interval into the normal range, quinidine restored the heart rate dependence of the QT interval toward a range of adaptation reported for normal subjects. Data from heterologous expression of wild‐type and mutant HERG genes indicate the mutation causes a 20‐fold increase in IC50 of d‐sotalol but only a 5.8‐fold increase in IC50 of quinidine.

Conclusion: Oral quinidine is effective in suppressing the gain of function in IKr responsible for some cases of short QT syndrome with a mutation in HERG and thus restoring normal rate dependence of the QT interval and rendering ventricular tachycardia/ventricular fibrillation noninducible.
Premature Ventricular Contraction‐Induced Concealed Mechanical Bradycardia and Dilated Cardiomyopathy:
Authors: SATISH ORUGANTI SAI , YEH KUAN‐HUNG , WEN MING‐SHIEN , WANG CHUN‐CHIEH
Published: January 2005

Left ventricular (LV) dysfunction due to frequent isolated premature ventricular contractions (PVCs) has been rarely reported. LV dysfunction and concealed mechanical bradycardia resolved in a patient with idiopathic dilated cardiomyopathy after the focal source of PVCs in the LV was eliminated by radiofrequency ablation (RFA). The patient remained free from PVCs and maintained normal LV function over 36‐month follow‐up. In a subset of patients with idiopathic dilated cardiomyopathy with frequent isolated PVCs, RFA of the arrhythmic focus restores normal LV function that can be long lasting.
Utility of Routine Follow‐Up Defibrillator Threshold Testing in Congenital Heart Disease and Pediatric Populations
Authors: STEPHENSON ELIZABETH A. , CECCHIN FRANK , WALSH EDWARD P. , BERUL CHARLES I.
Published: January 2005

Introduction: Recent studies have suggested that routine defibrillation threshold (DFT) testing of implantable cardioverter defibrillators (ICDs) in adults may not be necessary. The congenital heart disease and pediatric populations are a unique group of ICD recipients having a higher incidence of lead failure. We investigated the utility of follow‐up DFT testing in this population.

Methods and Results: The records of 155 ICD recipients at one center were retrospectively reviewed, and patients having one or more follow‐up DFT tests were analyzed. The patients were divided into two groups. The “routine” group consisted of 58 follow‐up DFT procedures in 46 patients, without known changes in ICD parameters. The “prompted” group consisted of 21 follow‐up DFT procedures in 18 patients, motivated by clinical concerns about changes in ICD lead status. Of 58 “routine” DFTs performed at a mean postimplant duration of 32 ± 23 months (range 2–78), 7 (12%) had reprogramming, and 1 required a hardware change as a result of the testing. Of the 21 “prompted” DFTs performed, 7 required device reprogramming, and 3 required hardware upgrade. Overall, 19 (24%) of 79 procedures detected clinically significant changes, requiring reprogramming or ICD system revision. No complications were seen from follow‐up DFT testing.

Conclusion: A high rate of abnormalities was found at follow‐up DFT testing in this population, especially in the group of patients with clinically prompted testing. Clinically indicated DFT testing, as expected, has a high yield of important information on device function in congenital heart disease and pediatric populations.
European Electron Induction Accelerators
Authors: Kaiser Herman F.
Published: January 2005

Betatrons, induction electron accelerators for the production of high energy X-radiation, were under development in Germany during the war and to a limited extent at present. This work is reviewed for the most part and details are given on the constructional features of 6- to 15-million volt betatrons and on the theory and design of 15- and 200-million volt betatrons. The smaller units, especially the Siemen's 6 Mv, are quite successful and more advanced than comparable American units. While no large machines were actually built, the projected 200-Mv Wideroe design introduces new features of value. Betatron patent ideas are reviewed.
An Apparatus for the Observation of the Kerr Effect with Microsecond Electrical Pulses
Authors: Kaye Wilbur , Devaney Richard
Published: January 2005

An apparatus for the observation of the Kerr electro-optic effect in liquids and polymers using microsecond electrical pulses, is presented and evaluated. This method offers a convenient way of studying internal motions and molecular configurations of polymeric material with a minimum of heating usually accompanying these observations. Electrical pulses of from 1- to 1000-microsecond width, 60–1000 p.p.s., at amplitudes up to 5000 volts are generated by conventional methods. These pulses are used to orient low molecular weight and polymeric materials placed between the plates of a condenser. The circular polarization induced in the polarized light passing between the plates actuates a photo-multiplier tube in order that the light pulses may be studied with an oscillograph.

Curves of Kerr constant versus temperature at temperatures to −80°C are compared with the literature. Oscillograms showing the response of several liquids and polymers are shown. Oscillograms showing an interesting difference between orientation and relaxation time are presented, as are oscillograms showing clearly both orientation and distortion polarization simultaneously.
Equations for the Inductances of Three-Phase Coaxial Busses Comprised of Square Tubular Conductors
Authors: Higgins Thomas James , Messinger Henry Peter
Published: January 2005

Equations are derived for calculating the associated inductances of the conductors of three-phase coaxial busses comprised of square tubular conductors. It is assumed that the conductors are nonmagnetic, are of such lengths that end effects are negligible, are right-cornered, and carry currents uniformly distributed over their cross sections. The general equations are obtained through use of geometric mean distance theory. Approximate equations, the conductors being considered as indefinitely thin, are epitomized in a table which yields values sufficiently accurate for most design work. In turn, these approximate equations are reduced to simple equations which also yield values sufficiently accurate for much design work. These equations for inductance lead to corresponding equations for the reactive voltage drops. Use of these various equations and the relative accuracy to be expected of them is illustrated by calculating the inductances and reactive voltage drops of typical busses.

The changes in the inductances due to rounding the edges of the conductors and the changes produced in both the inductances and the resistances by skin and proximity effects are investigated. The changes in the inductances due to rounding the edges can be approximated by use of a known equation. The changes in the inductances due to power frequency skin and proximity effects prove to be negligible; the changes in the resistances can be calculated by use of known skin-effect factors and newly derived proximity-effect factors.

Calculation of the inductances of three-phase coaxial busses constructed of tubular conductors made up of two channels or angles placed flange to flange is discussed. Finally, attention is called to a relatively little known means of obtaining balanced three-phase operation of geometrically unbalanced three-phase busses.
Mechanical Behavior of High Damping Metals
Authors: Zener Clarence
Published: January 2005

The relation between the various measures of internal friction are independent of the precise mechanism of the dissipation of energy when the internal friction is small, but not when it is large. In this paper the relation between the two measures most commonly used, logarithmic decrement and tangent of the angle with which strain lags behind stress, is deduced for all levels of internal friction in the important case in which the dissipation of energy is due to a relaxation process having a single time of relaxation. The conditions are further derived under which a specimen of such a metal will not vibrate, but returns aperiodically to its equilibrium configuration.
Acceleration of Electrons by a Resonant Cavity
Authors: Hereford Frank L.
Published: January 2005

Electrons were accelerated by means of a single resonant cavity operating at 75-cms wave-length. Energies as high as 0.75 Mev were attained by single-stage acceleration, the electrons entering the cavity at virtually zero velocity. By turning the emergent beam about, and reinjecting it into the cavity in the opposite direction two stage acceleration was achieved and 1.25-Mev electrons were produced. Possibilities of a ``shuttle accelerator'' are discussed.
Frequency Stabilization of Microwave Oscillators by Spectrum Lines
Authors: Smith William V. , De Quevedo José L. García , Carter R. L. , Bennett W. S.
Published: January 2005

A 2K50 microwave oscillator has been electronically coupled to the NH3 3,3 rotational spectrum line at 23,870 megacycles in such a manner as to maintain the frequency of the oscillator at the spectrum-line frequency. The theory of the ``spectrum-line discriminator'' designed to produce this frequency stabilization is developed.
On Cavity Formation in Water
Authors: Harvey E. Newton , McElroy Wm. D. , Whiteley A. H.
Published: January 2005

Phenomena involving the tensile strength of water have been studied by a kinetic method—high speed motion photography of the rapid movement of a blunt glass rod (5 mm diameter) in a narrow (16 mm inside diameter) glass tube of water. Special precautions have been taken to remove all hydrophobic patches and small gas masses (gas nuclei) but to retain the dissolved gas (air at one atmosphere) in the water. If the rod surface contained gas nuclei, or was hydrophobic and free of gas nuclei, cavitation occurred at the rear end when the velocity was less than 3 meters/sec., but if completely hydrophilic and free of gas nuclei, the velocity could be 37 meters/sec. or 83 miles/hour without cavitation. Addition of a detergent (diactyl sodium succinate) to the water did not prevent cavitation at a low velocity with the hydrophobic rod free of gas nuclei. Movement of a rod in pure corn syrup (viscosity 20.1 poises), free of gas nuclei, left a large cylindrical cavity that collapsed in a matter of hundredths of a second. It is not possible to calculate the tensions developed in these experiments, but it is pointed out that the velocities attained without cavitation are far higher than previously observed for movement of bodies in an aqueous medium, a result believed to be owing to the absence of all gas phases and hydrophobic surfaces.
Apparatus and Techniques for Practical Chemical Identification by X-Ray Diffraction
Authors: Smith Charles S. , Barrett Richard L.
Published: January 2005

The method of chemical identification by means of x-ray diffraction is reviewed from the point of view of apparatus and techniques recently made commonly available, with particular emphasis on the use of long wave-length x-radiation. Experience in using the A.S.T.M. card index file of x-ray diffraction data is reported. The discussion is designed especially for the person who wishes to make use of this important analysis tool but who is not an expert in x-ray diffraction.
Streamlines for the Subsonic Flow of a Compressible Fluid Past a Sphere
Authors: Van Driest E. R.
Published: January 2005

The second approximation to the velocity potential for the irrotational flow of a compressible fluid past a sphere, derived independently by Tamada and Kaplan, is used to calculate the subsonic streamlines for the flow of air at a Mach number of 0.5 past a sphere. Comparison is made between these streamlines and those for the irrotational flow of an incompressible fluid. Velocity and pressure comparisons are also shown.
The Effect of Hydrostatic Pressure on the Fracture of Brittle Substances
Authors: Bridgman P. W.
Published: January 2005

An arrangement is described permitting the fracture of brittle materials under the action of tensile stress superposed on hydrostatic pressure. The hydrostatic pressures range up to 30,000 kg/cm2. The tensile stress superposed on the pressure required to break Pyrex glass is a strong function of the material by which pressure is transmitted to the lateral surface of the glass, but in all cases of fracture produced at pressures above 25,000 kg/cm2 the net stress at fracture was compressive, that is, tensile fracture takes place against the direction of the stress. Beryllium and phosphor bronze lose the brittleness which characterize them at atmospheric pressure and fracture in tension under pressure after marked plastic deformation. Carboloy remains brittle in tension under pressure, but its tensile strength may increase by a factor of three. NaCl elongates plastically in tension under pressure with no obvious disturbance of the optical homogeneity. Pipestone remains completely brittle under pressure and of very low strength. In simple compression combined with hydrostatic pressure Pyrex glass increases greatly in strength. Single crystal Al2O3 under the same conditions exhibits plastic slip on the basal plane without fracture. In the discussion the importance of the condition of energy release as a factor controlling fracture is emphasized. The Griffith conception of fracture as resulting from stress concentration at the ends of microscopic cracks is consistent with many qualitative aspects of the situation, but probably cannot be carried through quantitatively.
X-Ray Scattering at Small Angles by Finely-Divided Solids. I. General Approximate Theory and Applications
Authors: Shull C. G. , Roess L. C.
Published: January 2005

The general approximate theory of x-ray scattering at small angles by finely divided solids is reviewed. It is assumed that the x-ray scattering data can be interpreted in terms of a particle size distribution, with particle-to-particle scattering negligible. Scattered intensity curves for Maxwellian, Gaussian, and rectangular size distributions are calculated, and several procedures for obtaining a size distribution from the experimental scattering data are described. Details of the experimental technique are given, and evidence is presented to show that appreciable error can result if crystal-monochromated radiation is not used. General procedures are given for applying corrections to the experimental data for the slit geometry used. Scattering data, mass distribution curves, and average particle sizes are presented for amorphous silica gels and for crystalline oxides of alumina, nickel and iron. These data are shown to correlate well with the results of crystal size measurements by x-ray diffraction line broadening and with specific surface measurements. The average particle size values determined from the experimental data are shown to have considerable significance, at least for the type of materials considered here.
X-Ray Scattering at Small Angles by Finely-Divided Solids. II. Exact Theory for Random Distributions of Spheroidal Particles
Authors: Roess L. C. , Shull C. G.
Published: January 2005

The theory of the scattering of x-rays at small angles is given for a continuous distribution in size of randomly spaced and oriented spheroidal particles having arbitrary, but fixed, shape. Families of scattering curves are presented for spheres, and for spheroids ranging in shape from flat disks to long rods. Both Maxwellian and rectangular types of particle mass distribution are used. A fit between the experimental and a calculated scattering curve enables one, under favorable circumstances, to determine the mass distribution in the test sample. However, an unambiguous interpretation of the experimental scattering curve on the basis of the small angle scattering theory is not possible without additional evidence from independent investigations of such quantities as particle shape and sample specific surface.
The Insulation of High Voltages in Vacuum
Authors: Trump John G. , Van De Graaff R. J.
Published: January 2005

Breakdown studies have been made between electrodes in high vacuum at constant voltages from 50 to 700 kv. These further demonstrate the inadequacy of the field emission theory to account generally for high voltage breakdown in vacuum. Experiments are described which investigate some of the ``total voltage'' breakdown mechanisms, including positive-ion emission by electron impact, electron emission by positive-ion impact and by photons. In the d.c. case these processes contribute to a steady interchange of charged particles between cathode and anode which increases with voltage until breakdown ensues. At higher breakdown voltages the cathode gradient has diminished far below the value for field emission. Measurements of electron emission by electrons with energies up to 300 kv for tungsten, steel, aluminum, and graphite are reported. The possibilities of predicting and of improving the insulating strength of electrode gaps in high vacuum by the study of the coefficients of the electrode materials are discussed.
The X-Ray Storage Properties of the Infra-Red Storage Phosphor and Application to Radiography
Authors: Berg O. E. , Kaiser H. F.
Published: January 2005

An application of the characteristics of infra-red storage phosphors to radiography is described, whereby the expense and trouble of x-ray film processing may be partially or completely eliminated. The properties of these materials to store x-ray energy for periods of time and release that energy upon exposure to infra-red radiation have proved practical for either temporary and permanent recording of the latent x-ray image. One distinct feature of this method is the complete removal of harmful x-radiation to the technician. The possibility of a new field of radiography in ``flash fluoroscopy'' is also suggested by the authors. Graphs and charts exhibiting the characteristic behavior of infra-red phosphors to x-ray energy are included as well as actual photographs and radiographs comparing radiography with phosphorography.
The Speed of Propagation of Brittle Cracks in Steel
Authors: Hudson G. , Greenfield M.
Published: January 2005

Brittle failure was produced in notched steel tensile specimens. The speed of propagation of the brittle crack was measured and found to be approximately 40,400 in./sec.
Use of the Broadcast Band in Geologic Mapping
Authors: Kerwin Larkin
Published: January 2005

A review of the literature indicates that a method of geologic mapping by means of observing the effect of geologic anomalies on electromagnetic field intensity should be practical. Field equipment is designed and assembled for that purpose and proves accurate and simple to use. Preliminary investigations with it successfully locate several anomalies.
Torsion of a Rubber Cylinder
Authors: Rivlin R. S.
Published: January 2005

It has been predicted theoretically that, in general, a right-circular cylinder of incompressible, highly elastic material, which is isotropic in its undeformed state, cannot be held in a state of pure torsional deformation by means of a torsional couple alone. In addition, normal surface tractions must be exerted over the plane ends of the cylinder. These normal surface tractions depend on the amount of torsion and on position on the plane ends of the cylinder. Experiments are reported here in which this phenomenon is observed in a right-circular cylinder of pure gum compound. The dependence of the surface traction on amount of torsion and its distribution over the surface of the cylinder is studied by measuring the bulging of the rubber into small holes in a metal plate on one end of the cylinder.
Electrical Conductivity of GR-S and Natural Rubber Stocks Loaded with Shawinigan and R-40 Blacks
Authors: Wack P. E. , Anthony R. L. , Guth E.
Published: January 2005

Measurements have been made of the direct current conductivity of rubbers loaded with carbon black. Shawinigan and Continental R-40 blacks compounded in natural rubber and GR-S were studied, and the resistivities were determined as functions of time, temperature, concentration and elongation. Resistance decreased with time, at first very rapidly, then more slowly, approaching an equilibrium value. This behavior seems to be independent of the type of black used. Temperature coefficients of resistance (at 50°C) were positive for Shawinigan stocks, negative for samples containing R-40, and tended to increase with increasing concentration of black and with increasing extension of the sample. At low concentrations, R-40 gave higher conductance in GR-S than did Shawinigan. At high loadings, Shawinigan gave the higher conductance in both GR-S and natural rubber. Resistance increased with elongation for all stocks containing R-40. The Shawinigan GR-S samples showed an inversion; for small elongations the resistance increased on stretching, but for higher extensions the resistance decreased. The results are interpreted on the assumption that the carbon black tends to form chains in the rubber matrix.