bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between chain collapse and secondary structure formation in a partially folded protein
Authors: Nakagawa Kanako , Yamada Yoshiteru , Matsumura Yoshitaka , Tsukamoto Seiichi , Yamamoto‐Ohtomo Mio , Ohtomo Hideaki , Okabe Takahiro , Fujiwara Kazuo , Ikeguchi Masamichi
Published: October 2013

Chain collapse and secondary structure formation are frequently observed during the early stages of protein folding. Is the chain collapse brought about by interactions between secondary structure units or is it due to polymer behavior in a poor solvent (coil‐globule transition)? To answer this question, we measured small‐angle X‐ray scattering for a series of β‐lactoglobulin mutants under conditions in which they assume a partially folded state analogous to the folding intermediates. Mutants that were designed to disrupt the secondary structure units showed the gyration radii similar to that of the wild type protein, indicating that chain collapse is due to coil‐globule transitions. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 651–658, 2014.
Age‐related differences in auditory evoked potentials as a function of task modulation during speech–nonspeech processing
Authors: Rufener Katharina Simone , Liem Franziskus , Meyer Martin
Published: October 2013

Background

Healthy aging is typically associated with impairment in various cognitive abilities such as memory, selective attention or executive functions. Less well observed is the fact that also language functions in general and speech processing in particular seems to be affected by age. This impairment is partly caused by pathologies of the peripheral auditory nervous system and central auditory decline and in some part also by a cognitive decay.

Aims

This cross‐sectional electroencephalography (EEG) study investigates temporally early electrophysiological correlates of auditory related selective attention in young (20–32 years) and older (60–74 years) healthy adults.

Material and methods

In two independent tasks, we systematically modulate the subjects' focus of attention by presenting words and pseudowords as targets and white noise stimuli as distractors.

Results

Behavioral data showed no difference in task accuracy between the two age samples irrespective of the modulation of attention. However, our work is the first to show that the N1‐ and the P2 component evoked by speech and nonspeech stimuli are specifically modulated in older adults and young adults depending on the subjects' focus of attention.

Conclusion

This finding is particularly interesting in that the age‐related differences in AEPs may be reflecting levels of processing that are not mirrored by the behavioral measurements.
BRD4 associates with p53 in DNMT3A‐mutated leukemia cells and is implicated in apoptosis by the bromodomain inhibitor JQ1
Authors: Stewart Helen Jayne Susan , Horne Gillian Abigail , Bastow Sarah , Chevassut Timothy James Telfer
Published: October 2013

The bromodomain and extra terminal (BET) family protein bromodomain containing protein 4 (BRD4) is an epigenetic regulator recently identified as a therapeutic target for several hematological cancers, notably mixed lineage leukemia‐fusion acute myeloid leukemia (MLL‐AML). Here, we show that the BRD4 bromodomain inhibitor JQ1 is highly active against the p53‐wild‐type Ontario Cancer Institute (OCI)‐AML3 cell line which carries mutations in nucleophosmin (NPM1) and DNA methyltransferase 3 (DNMT3A) genes commonly associated with poor prognostic disease. We find that JQ1 causes caspase 3/7‐mediated apoptosis and DNA damage response in these cells. In combination studies, we show that histone deacetylase (HDAC) inhibitors, the HDM2 inhibitor Nutlin‐3, and the anthracycline daunorubicin all enhance the apoptotic response of JQ1. These compounds all induce activation of p53 suggesting that JQ1 might sensitize AML cells to p53‐mediated cell death. In further experiments, we show that BRD4 associates with acetylated p53 but that this association is not inhibited by JQ1 indicating that the protein–protein interaction does not involve bromodomain binding of acetylated lysines. Instead, we propose that JQ1 acts to prevent BRD4‐mediated recruitment of p53 to chromatin targets following its activation in OCI‐AML3 cells resulting in cell cycle arrest and apoptosis in a c‐MYC‐independent manner. Our data suggest that BET bromodomain inhibition might enhance current chemotherapy strategies in AML, notably in poor‐risk DNMT3A/NPM1‐mutated disease.
Strain‐Promoted Azide–Alkyne Cycloaddition with Ruthenium(II)–Azido Complexes
Authors: Cruchter Thomas , Harms Klaus , Meggers Eric
Published: October 2013

The reactivity of an exemplary ruthenium(II)–azido complex towards non‐activated, electron‐deficient, and towards strain‐activated alkynes at room temperature and low millimolar azide and alkyne concentrations has been investigated. Non‐activated terminal and internal alkynes failed to react under such conditions, even under copper(I) catalysis conditions. In contrast, as expected, rapid cycloaddition was observed with electron‐deficient dimethyl acetylenedicarboxylate (DMAD) as the dipolarophile. Since DMAD and related propargylic esters are excellent Michael acceptors and thus unsuitable for biological applications, we investigated the reactivity of the azido complex towards cycloaddition with derivatives of cyclooctyne (OCT), bicyclo[6.1.0]non‐4‐yne (BCN), and azadibenzocyclooctyne (ADIBO). While no reaction could be observed in the case of the less strained cyclooctyne OCT, the highly strained cyclooctynes BCN and ADIBO readily reacted with the azido complex, providing the corresponding stable triazolato complexes, which were amenable to purification by conventional silica gel column chromatography. An X‐ray crystal structure of an ADIBO cycloadduct was obtained and verified that the formed 1,2,3‐triazolato ligand coordinates the metal center through the central N2 atom. Importantly, the determined second‐order rate constant for the ADIBO cycloaddition with the azido complex (k2=6.9 × 10−2 M−1 s−1) is comparable to the rate determined for the ADIBO cycloaddition with organic benzyl azide (k2=4.0 × 10−1 M−1 s−1). Our results demonstrate that it is possible to transfer the concept of strain‐promoted azide–alkyne cycloaddition (SPAAC) from purely organic azides to metal‐coordinated azido ligands. The favorable reaction kinetics for the ADIBO‐azido‐ligand cycloaddition and the well‐proven bioorthogonality of strain‐activated alkynes should pave the way for applications in living biological systems.
Functionalized Polymer‐Based Spherical Activated Carbon for Liquid and Gas Phase Applications
Authors: Schrage Christian , Modrow Antje , Fichtner Sven , Giebelhausen Jann Michael , Böhringer Bertram
Published: October 2013

Polymerbasierte sphärische Aktivkohle (PBSAK) kann durch die Integration von reaktiven Komponenten in das Porensystem funktionalisiert werden. Dadurch erschließen sich neue Anwendungsbereiche für diese Adsorbentien. So kann imprägnierte PBSAK als Breitbandsorbens für Atemschutzanwendungen und zur Entfernung von Metallen aus belastetem Wasser eingesetzt werden, während stickstofffunktionalisierte PBSAK für die Reinigung von Gasströmen gut geeignet ist. Außerdem können oberflächenmodifizierte PBSAK zur Gewinnung von Wertstoffen wie Gold oder Uran eingesetzt werden.
Kinetic Separation of Methane Containing Gas Mixtures via Carbon Molecular Sieves
Authors: Möller Andreas , Guderian Joachim , Möllmer Jens , Lange Marcus , Hofmann Jörg , Gläser Roger
Published: October 2013

Die Erzeugung von Biomethan in Erdgasqualität aus methanhaltigen Gasgemischen ist ein wichtiger Beitrag im Rahmen der Nutzung erneuerbarer Energien. Hierzu können thermische Trennverfahren wie Gaswäschen, Adsorptions‐ und Membrantrennverfahren eingesetzt werden. Bei Verwendung des Adsorptionsverfahrens werden die Hauptkomponenten Methan und Kohlendioxid unter Ausnutzung des kinetischen Effektes an Kohlenstoffmolekularsieben separiert. Hierbei adsorbiert CO2 an der inneren Oberfläche der Kohlenstoffmolekularsiebe, während CH4 aufgrund der sehr langsamen Kinetik in der Gasphase verbleibt. Für die Bewertung der Materialien und der Effektivität des Gesamtprozesses müssen sowohl die Gleichgewichtsbeladungen als auch die kinetischen Kenngrößen bekannt sein.
Effects of metoprolol on heart rate in patients with digitalis treated chronic atrial fibrillation
Authors: Khalsa A. , Edvardsson N. , Olsson S. B.
Published: October 2013

Adequate control of ventricular rate in patients with chronic atrial fibrillation (AF) may not be achieved with digitalis alone. In the present study the additional effect of two different doses (50 mg and 50 + 50 mg) of oral metoprolol, a new selective β‐blocking agent, on ventricular rate in patients with longstanding AF has been studied. A decrease in the mean ventricular rate during rest and during exercise at various work loads was observed after both doses. The effect was more pronounced at the highest work load of 80 W, both after 50 mg (p < 0.002) and after 50 + 50 mg (p < 0.01) of the drug. A high initial heart rate at rest or during exercise was reduced more by the drug than a lower one. Exercise tolerance was reduced in 2 patients. These results suggest that patients with AF in whom satisfactory control of heart rate cannot be achieved with digitalis alone may benefit from addition of individualized metoprolol therapy.
Evaluation of sinus node automaticity and sinoatrial conduction in children with normal and abnormal sinus node function
Authors: Yabek S. M.
Published: October 2013

Sinus node recovery time (SNRT) and sinoatrial conduction time (SACT) were determined in each of 28 children. Eighteen children (ages 2 to 14 years) had electrocardiographically normal sinus node function and served as controls. Ten children (ages 4 to 13 years) had electrocardiographic evidence of sinus node dysfunction, consisting of inappropriate sinus bradycardia, periods of sinus arrest or sinoatrial exit block. Mean control SNRT was 133% of the sinus cycle length with an upper normal limit of 151% (mean + 2 SD). Control SACTs ranged from 45‐105 ms with mean and mean + 2 SD values of 71 ms und 105 ms.

In the patients with SND, SNRTs averaged 168% and five patients had abnormally prolonged values of 158 to 256%. Mean SACT was 101 ms with four children having values greater than 105 ms. Seven of the 10 patients with SND had at least one electrophysiologic abnormality.

This study defines normal sinoatrial conduction in children and validates the data by demonstrating a close correlation with similar data obtained from adult populations. Although abnormal electrophysiologic data confirms the presence of sinus node dysfunction, normal values for SNRT and SACT do not insure normal sinus node function.
Angiographic restudy of coronary artery bypass grafts simplified by a marker
Authors: Halseth W. L. , Elliott D. P. , Walker E. L. , Meza F.
Published: October 2013

This study was done to examine the benefit of utilizing a stainless steel circumferential aorta‐saphenous vein anastomosis marker.

Cardiac catheterization was performed in 87 patients following coronary artery bypass surgery. The exact aorta saphenous anastomotic site was quickly identified and successfully injected in 100% of the patients. During operation stainless steel circumferential markers were placed around the anastomotic site in 1,061 consecutive patients with 3,367 grafts. There was no early or late morbidity or complication from the circumferential markers.
Significance of the negative exercise test in evaluation of patients with chest pain
Authors: Weisburst M. R. , Most A. S. , Williams D. O.
Published: October 2013

Fifty‐three patients with chest pain and a negative exercise test at greater than 85% predicted maximal heart rate underwent coronary arteriography. Twenty‐one patients (40%) had significant luminal narrowing in one or two vessels. No patient had left main disease. Pathologic electrocardiographic Q waves were present in only coronary heart disease patients (p < 0.001). There was no difference (p > 0.05) in prevalence of T wave abnormalities, chest pain or ventricular beats during exercise in patients with or without coronary disease. Analysis of sex distribution revealed that typical angina pectoris was uncommon in the women (p < 0.001) and all twenty‐one coronary patients were men (p < 0.001). We conclude that in patients with chest pain and a negative exercise test, three vessel or left main coronary artery disease is unlikely. Also, women with atypical chest pain and a negative exercise test are unlikely to have a fixed coronary obstruction.
Prodromal characteristics as indicators of cardiac events in patients hospitalized for chest pain
Authors: Schroeder J. S. , Lamb I. H. , Hu M.
Published: October 2013

In an effort to determine the usefulness of prodromata for predicting a myocardial infarction, a prospective analysis was made of 211 consecutive patients with chest pain who were admitted to the Stanford University Medical Center Coronary Care Unit. In their subsequent course, 91 patients had a myocardial infarction, 102 had a myocardial infarction ruled‐out, and 18 had a noncardiac etiology for their chest pain. Prodromal chest pain in the previous six months had occurred in 65% of patients and unstable angina in 61%. Infarction versus noninfarction patient groups could not be identified on the basis of prodromal ill health, chest pain, unstable angina, typical versus atypical nature of the chest pain, or activity at the onset of pain. Complaints of preceding fatigue and increased perceived stress were common in both groups. Activity at the onset of the admission chest pain was strenuous in 15% of the infarction patients and 12% of the noninfarction patients. We conclude that prodromal symptoms are common in both infarction and noninfarction patients. Although chest pain probably remains the single most frequent identifier of a new cardiac event, it is common in noninfarction patients and cannot be used alone to predict infarction or death.
A previously unrecognized drug interaction between quinidine and digoxin
Authors: Reiffel J. A. , Leahey E. B. , Drusin R. E. , Heissenbuttel R. H. , Lovejoy W. , Bigger J. T.
Published: October 2013

Following the development of digoxin radioimmunoassay, we noted that serum digoxin concentrations appeared to rise in patients given quinidine. To further evaluate this important possible interaction between digoxin and quinidine, charts from 863 cardiology patients were reviewed. Ninety two patients received both drugs after having been on digoxin alone; 38 were ineligible for the study because of insufficient data and 27 were excluded because of changing renal function and/or concomitant antiarrhythmic drug therapy, leaving 27. Serum digoxin increased in 25 of the 27 study patients (93%) during quinidine therapy; mean serum digoxin rose from 1.4 ng/ml before quinidine to 3.2 ng/ml during quinidine. Anorexia, nausea and/or vomiting developed in 16 patients (59%) during quinidine therapy, but disappeared in all 10 patients in whom digoxin alone was reduced in dose, suggesting that digoxin had a causative role in the appearance of these symptoms although they developed only after quinidine had begun. Three of thirteen patients with only atrial arrhythmias on digoxin prior to quinidine developed new ventricular premature depolarizations (VPD) after starting quinidine; two of these three as well as four patients with prior VPDs developed new ventricular tachycardia, ventricular fibrillation, asystole, or sudden death. When starting quinidine in patients who are taking digoxin, the clinical course, ECG and serum digoxin should be followed closely.
Aneurysm of the left atrial appendage
Authors: van der Hauwaert L. G. , Dumoulin M. , Daenen W. , Stalpaert G.
Published: October 2013

A 2‐year old asymptomatic girl is presented in whom the chest x‐ray film led to the discovery of a grossly distorted cardiac shadow. Angiocardiography showed a giant aneurysm originating from the left atrium. At operation an intrapericardial aneurysm of the left atrial appendage, measuring 12 × 4 × 4 cm, was found. It communicated with the left atrium through an orifice measuring 3 cm. The aneurysm was excised.
Atrial bigeminy with block associated with bradycardia and paroxysmal atrial fibrillation — An important variant of the tachycardia‐bradycardia syndrome
Authors: Washington H. G. , Ward D. E. , Camm A. J. , Spurrell R. A. J.
Published: October 2013

Serial 2‐channel 24 h dynamic ECGs in 7 patients who were referred with the “tachy‐brady” syndrome for consideration for permanent cardiac pacing revealed:

1. atrial premature beats (APBs) which were conducted to the ventricles normally or aberrantly;

2. intermittent atrial bigeminy with block towards the ventricles (this rhythm mimicked sinus bradycardia with ventricular rates of 38‐45 beats/min and the ectopic P waves were visible on only one of the ECG channels);

3. paroxysms of atrial fibrillation initiated by closely coupled APBs.

These findings suggested that both the ventricular bradycardia and the atrial fibrillation were caused by frequent APBs and that pacing therapy was unnecessary. Disopyramide was given to 5 patients resulting in suppression of the arrhythmia and relief of symptoms. In one patient there was spontaneous resolution and one patient refused treatment. This variant of the “tachy‐brady” syndrome can be successfully treated by suppression of abnormal atrial impulse formation without recourse to pacemaker implantation.
The superiority of mitral E point‐ventricular septum separation to other echocardiographic indicators of left ventricular performance
Authors: D'Cruz I. A. , Lalmalani G. G. , Sambasivan V. , Cohen H. C. , Glick G.
Published: October 2013

M‐mode echocardiography, angiocardiography, and coronary arteriography were done in 40 patients with coronary heart disease, 12 with congestive cardiomyopathy, and 14 with no detectable cardiac or coronary abnormality. We measured mitral E point‐ventricular septum separation (EPSS) at the moment of the E peak; the previously described method measures EPSS as the vertical distance between the nadir of systolic septal motion and the subsequent mitral E peak. Angiocardiographic ejection fractions correlated better with EPSS (r = 0.83) than with left ventricular (LV) end‐diastolic internal diameter (r = 0.62), LV internal diameter systolic shortening fraction (r = 0.64), LV echocardiographic ejection fraction (r = 0.70), and LV posterior wall systolic thickening (r = 0.58). Patients with angiocardiographic ejection fractions below 55% usually had EPSS values over 10 mm by our method. Six false negatives and one false positive occurred. Our observations in patients with impaired LV performance suggest that LV dilatation, and especially dilatation of the LV outflow tract, is relatively more important than reduction in the amplitude of diastolic anterior mitral excursion in the production of high EPSS values. Although the usual method for measuring EPSS and ours are equally satisfactory, ours has certain theoretical advantages.
Human electropharmacology of the calcium antagonist dimeditiapramine (Ro 11‐1781) in coronary patients
Authors: Cocco G. , Strozzi C. , Chu D.
Published: October 2013

The electrophysiological effect of dimeditiapramine (Ro 11‐1781), a Ca2+ antagonist, was evaluated in 20 patients with coronary heart disease. Electrophysiological measurements, including sinus cycle length, sinoatrial conduction time, intra‐atrial conduction time, atrial, atrioventricular, nodal and ventricular refractory periods and intraventricular conduction time were recorded before and after the intravenous administration of Ro 11‐1781. At a dose which is effective against cardiac arrhythmias, Ro 11‐1781 produced no statistically significant changes in the sinoatrial and intraventricular conduction time. Similarly, neither the sinoatrial nor the ventricular refractory period was affected. Ro 11‐1781, however, increased the atrioventricular conduction time and decreased the systolic blood pressure to a statistically significant extent. The tolerance was very good.
Concealed extrasystoles due to wenckebach conduction delay within the reentry loop
Authors: Kerin N. Z. , Levy M. N. , Goldberg L. B. , Rubenfire M.
Published: October 2013

Long electrocardiographic strips were analyzed from an aged patient whose heart rhythm had periods of unifocal ventricular extrasystoles with fixed coupling intervals. Periods of gradual prolongation of the coupling interval finally led to omission of a ventricular premature beat. This sequence was repetitive and is considered to be the result of reentrant extrasystoles with a 3:2 Wenckebach type of conduction delay within the reentry loop. The mechanism of concealed conduction due to overlong propagation within the reentry loop is discussed.
Validity of myocardial oxygen consumption parameters
Authors: Baller D. , Bretschneider H. J. , Hellige G.
Published: October 2013

The purpose of this study was to examine any reported indices for estimating myocardial oxygen consumption (MV̇O2) under uniform experimental conditions at maximal variation of hemodynamics and MV̇O2. One hundred sixty‐two steady states were analyzed in 10 closed‐chest dog experiments. Myocardial blood flow was directly measured by a differential pressure catheter in the coronary sinus. The indirect values of MV̇O2 calculated from 24 indices were compared with directly measured MV̇O2. Throughout a wide range of hemodynamic states, the best correlate with MV̇O2 was found to be the additive parameter Et (r = 0.96). Any indices that do not incorporate potentially important changes of MV̇O2 related to both myocardial contractility and ventricular dimensions show unsatisfactory correlations with MV̇O2 at extreme changes of hemodynamics. Tension‐time index (TTI) correlates poorly with MV̇O2 (r = 0.63). This result is due to the neglect of contractility. Pressure‐heart rate product (P × HR) correlates with MV̇O2 with r = 0.86. Better results for TTI and P × HR, as reported in previous works, are reproducible by dividing our data into two groups of different inotropic states. At normal and moderate inotropic stimulation the correlation for TTI rises to r = 0.96, and for P × HR to r = 0.91. This augmentation is to be referred to the close relationship (r = 0.92) of peak ventricular pressure to maximum rate of pressure rise in this group. The additive parameter Et is the best, both at moderate (r = 0.97) and at maximal inotropic stimulation (r = 0.87), and is to be preferred for indirect estimation of MV̇O2. Results are discussed with regard to the clinical application of MV̇O2 indices.
A comparison of mathematical models for estimating right ventricular volumes in animals and man
Authors: Horn V. , Mullins C. B. , Saffer S. I. , Jones D. C. , Freeborn W. A. , Knapp R. S. , Nixon J. V.
Published: October 2013

Volume of 19 right ventricular canine casts and 11 right ventricular human casts were obtained by water displacement and compared to three different mathematical models for estimating right ventricular volumes by biplane cineangiography. In the canine studies, significant linear correlation coefficients were obtained using the longest measured length method (r = 0.92), the triangular modification of Simpson's rule (r = 0.93), and the elliptical modification of Simpson's rule (r = 0.93). The human studies resulted in similar significant correlation coefficients of 0.96, 0.97, and 0.97, respectively. Although the highest correlation with the lowest standard error of estimate was obtained using the triangular model, all three mathematical models produced volume estimations that fell within acceptable biological limits of accuracy.
Predictive value of thallium scintigraphy in coronary artery disease
Authors: Schicha H. , Rentrop P. , Facorro L. , Karsch K. R. , Blanke H. , Kreuzer H. , Emrich D.
Published: October 2013

To verify the predictive value of thallium exercise scintigraphy, 20 normal individuals and 60 patients with coronary artery disease (CAD) were examined, using a quantitative standard technique and receiver operating characteristic analysis. The sensitivity of thallium scintigraphy for the presence of CAD was 97% for patients with previous infarction and 85% for those without infarction. The sensitivity for the extent of CAD was 93% for vessels perfusing infarcted areas and only 67% for vessels without infarction. In patients without myocardial infarction, sensitivity for the number of diseased vessels decreased with increasing extent of CAD. An underestimation of hemodynamically significant stenoses was proven by a comparison with the results of exercise ventriculography.

The predictive value of a normal scintigram at a high prevalence of CAD is as low as the predictive value of an abnormal scintigram at a low prevalence level (screening). Thallium scintigraphy is indicated in patients with a medium prevalence of CAD, e.g., in patients with atypical angina and in asymptomatic patients with pathologic ECG.
States of myocardial metabolism related to ischemia
Authors: Kammermeier H. , Giesen J.
Published: October 2013

Energy metabolism of the heart in ischemia is mainly characterized by oxygen deficiency and lack of lactate removal. However, under certain circumstances substrate deficiency might contribute to disturbances of energy supply as well. Capillary permeability was determined from tracer washout kinetics of isolated hearts. Regulation of mitochondrial respiration was estimated from the relationship of phosphorylation potential vs. oxygen consumption. The results obtained suggest that at least under experimental conditions substrate supply at the level of capillary exchange can be a rate‐limiting figure, as well as substrate supply at the mitochondrial level, i.e., NADH supply. The latter was inferred from the effects of cobalt and strontium ions on the regulation of respiration.
Causes and effects of noncompliance in cardiac patients
Authors: Sampson J. J. , Arbona C. L.
Published: October 2013

This study affirms that compliance with medical regimen in a university cardiac clinic favorably influences patient outcome. The multiplicity of factors influencing compliance are emphasized, as is the need for continuing physician evaluation of compliance, and attempts to favorably influence it.
Segmental early relaxation phenomenon (SERP) versus exercise‐induced hypokinesia: A correlation study
Authors: Trieb G. , Sigwart U. , Mannebach H. , Gleichmann U.
Published: October 2013

Sixty‐one of five hundred thirty‐five patients (11%) with‐coronary heart disease (CHD) had a segmental early relaxation phenomenon (SERP). Thirty‐four patients had evidence of previous myocardial infarction (29 inferior and 5 lateral). Only 10 of 137 subjects (7%) with no evidence of CHD had a SERP. The review of coronary angiograms showed a high incidence of SERP in patients with left anterior descending coronary artery stenoses, particularly in the presence of additional high‐grade stenosis of the circumflex branch. Also SERP can be observed frequently in patients with triple‐vessel disease and inferior myocardial infarction. A circumscript SERP of the anterolateral or high septal wall is likely to be associated with ischemia of the corresponding myocardial segment; this hypothesis is supported by hemodynamic and angiographic measurements during exercise.

An abnormal increase in left ventricular end‐diastolic pressure (LVEDP), augmentation of left ventricular end‐diastolic volume index (LVEDVI), and decrease in left ventricular ejection fraction (LVEF) with exercise was noted in 33 patients with SERP and normal resting left ventricular angiogram (Fig. 1).

There is no adequate hypothesis to explain SERP in subjects without evidence of coronary heart disease. In some instances abnormal increase in LVEDP in the absence of significant coronary artery lesions was seen in these cases. Local metabolic disorders secondary to myocardial disease might be the underlying cause.
Diagnostics of ischemic heart disease: Influence of myocardial ischemia on AMP catabolite release and hemodynamics
Authors: de Jong J. W. , Verdouw P. D. , Remme W. J. , Simoons M. L. , Stam H.
Published: October 2013

The purpose of this study was to answer the questions: What is the correlation between adenosine monophosphate (AMP) breakdown and hemodynamic changes caused by myocardial ischemia? Can AMP catabolites released by the heart be used to diagnose ischemic heart disease?

We studied changes in metabolism and hemodynamics in the intact ischemic pig heart and the isolated, perfused rat heart made hypoxic or ischemic. We measured the AMP catabolites adenosine, inosine, and hypoxanthine, which were released by the oxygen‐deprived heart.

Inosine is a sensitive (and early) indicator of wall‐thickness changes in the ischemic pig heart. In addition to a change in lactate metabolism, myocardial inosine production is a good marker for myocardial ischemia because it correlates well with carbohydrate extraction and ventricular function, and because these occlusion‐induced changes are relatively large. We tried unsuccessfully to develop a model to study interventions during myocardial ischemia in which the pig served as its own control.
Role of nuclear cardiology in differentiating scar from ischemic myocardium
Authors: Schmidt D. H. , Hellman C. K. , Johnson W. D.
Published: October 2013

For 10 years, patients with abnormal ventricular function (sometimes with ejection fractions under 10%) have generally been offered surgery. Significant improvement in ejection fraction, or in wall motion in a specific segment, has often been observed postoperatively. In the past, simple and effective means to differentiate preoperatively which areas will improve (ischemic myocardium) from those which will not (scar tissue) have not been available. Several radionuclide techniques have been used to study the problems, including use of radio‐labeled particles, 201thallium, 133xenon, and first‐pass radionuclide angiography with and without nitroglycerin intervention. Only the last technique has proven reliable in predicting postoperative improvement in wall motion.

Thirty patients have been studied with routine catheterization and first‐pass radionuclide angiography and all had significant wall motion abnormalities preoperatively. Preoperative radionuclide angiograms with nitroglycerin have been compared with postoperative radionuclide angiograms. The images of the RAO radionuclide angiogram were divided into six segments for analysis of wall motion by trisecting the long axis of the left ventricle. Results show that nitroglycerin accurately predicts improvement in ejection fraction with surgery. In terms of wall motion, approximately 50% of akinetic segments improve and 65% of hypokinetic segments improve both with nitroglycerin and revascularization.

To summarize, nitroglycerin predicts wall motion improvement with 80% sensitivity and 90% specificity. These data suggest that nitroglycerin radionuclide angiography is a safe, noninvasive technique for differentiating ischemic viable muscle from scar tissue.
Ten‐year experience of 359 epicardial pacemaker systems: Complications and results
Authors: Oldershaw P. J. , Sutton M.G. , Ward D. , Jones S. , Miller H.
Published: October 2013

In the last ten years (1970–1980) 457 patients underwent permanent pacemaker insertion in the Brompton Hospital. Our practice has been somewhat atypical in that the majority of these patients had epicardial leads, initially using a Cordis intramural sutured electrode (85 patients), and subsequently a Medtronic sutureless electrode (274 patients). Our initial experience with these electrodes was satisfactory, but more recently it has become apparent that the long‐term morbidity and complication rate is high. The respective complication rates being 25% and 18% for sutured and sutureless epicardial electrodes. In this study, lead complications were defined as those requiring lead replacement, and problems most commonly encountered were high voltage threshold, infection, and lead fracture. Unless there are specific indications for epicardial pacing it is now our policy to treat patients requiring permanent pacing with endocardial systems. Our complication rate with this technique (90 patients) is significantly lower (9%).
Myopotential inhibition of ventricular synchronous pacemaker
Authors: Lazar A. V. , Massumi A. , Hall R. J.
Published: October 2013

Unlike ventricular inhibited demand pacemakers, myopotential inhibition of ventricular synchronous pacemaker is a less well recognized phenomenon. We describe a case of slowing of the pacing rate of an Intermedics Cyberlith pulse generator in the R‐synchronous mode, below the programmed rate from myopotential inhibition.
The cardiac fibrous skeletal ring model: Simple, inexpensive method to illustrate normal and abnormal cardiac anatomy three dimensionally
Authors: Chun P. K. C.
Published: October 2013

A novel, innovative, simple, and inexpensive graphic method is proposed to facilitate illustrating the variety of cardiovascular pathology. Six‐ring plastic container holders, resected selectively, or circles carefully drawn to represent the cardiac fibrous skeleton, enable visualization of the cardiac pathology three‐dimensionally without notations. Given 9 axioms, this systematic technique is easy to learn and teach, enabling a nonartistic neophyte to understand complex, cardiac anatomic perspectives and diagram specific cardiac anomalies.
Left ventricular emptying dynamics in patients with asymmetric septal hypertrophy and concentric hypertrophic cardiomyopathy
Authors: Peters J. , Bhargava V. , Johnson A. , Mangiardi L. , Slutsky R.
Published: October 2013

We studied the dynamics of left ventricular (LV) emptying in 8 patients with asymmetric septal hypertrophy (ASH), 6 patients with concentric hypertrophic cardiomyopathy (CHC), and 6 normal controls. Four patients with ASH had resting systolic gradients >20 mmHg, all had significant post premature ventricular contraction (PVC) systolic pressure gradients. LV volume (V) was obtained by frame‐by‐frame analysis of cineangiograms. End‐diastolic volume was similar for all groups; end‐systolic volume was significantly less in ASH and CHC patients than in normals. Maximum dV/dt was similar in ASH and CHC, and significantly greater than normals. Total systolic contraction time (SCT), i.e., time from peak volume to last cine frame at minimum volume, was similar for all groups, but the time required to eject 90% of stroke volume (90%T), as a fraction of SCT, was shorter for ASH (0.52±0.07) and CHC patients (0.51 ±0.05) than normals (0.67±0.07) (p < 0.05 vs myopathy groups). In the sinus beat following a PVC, however, this ratio decreased significantly in normals and CHC patients, but did not change in ASH patients. We conclude that ASH and CHC have similar exaggerated systolic LV ejection dynamics in the basal state; the failure of ASH patients with post‐PVC systolic outflow gradient to reduce 90% T/SCT post PVC may reflect obstruction to LV emptying.
Chromatin changes of endothelial cells in umbilical arteries in smokers
Authors: Asmussen I.
Published: October 2013

Fine granular spots within the nucleus of endothelial cells have been demonstrated in umbilical arteries from newborns. These nuclear changes were predominantly found in vessels from newborns delivered by heavy smoking mothers (≥ 10 cigarettes per day) χ2 = 8.28, p < 0.005. Similar nuclear changes have until now only been reported in man in relation to tumors or other pathological conditions. The vessels showed signs of increased cellular turnover compatible with the findings in experimental atherosclerosis. The nuclear changes thus could be interpreted as an alteration of nuclear activity.
The relationship of low voltage on the electrocardiogram and chronic obstructive pulmonary disease
Authors: Sorbello A. , Giudice J. C. , Papa L.A.
Published: October 2013

A retrospective analysis was performed to analyze the relationship between low voltage on the electrocardiogram and chronic obstructive pulmonary disease. Subjects were 250 patients who had both pulmonary function tests and an electrocardiogram at UMDNJ‐John F. Kennedy Memorial Hospital from the years 1975–1980. Low voltage was detected in only 13 of 250 patients. An attempt to define the relationship between the incidence of low voltage on the electrocardiogram and the severity of airway obstruction, as judged by the reduction in the FEV1, was unsuccessful. Concomitantly, a relationship could not be established between the incidence of low voltage and the degree of hyperinflation, as judged by the residual volume. In conclusion, the electrocardiographic evidence of low voltage does not represent either a sensitive or a specific finding for patients with chronic obstructive lung disease. It cannot be construed as either a useful or predictive parameter in the diagnostic evaluation of these patients.
Temperature Dependence of the Properties of Water and Its Solutes, Including the Supercooled Region
Authors: Sluyters Jan H. , Sluyters‐Rehbach Margaretha
Published: October 2013

An earlier study on the properties of supercooled water and some solutes obtained by simple graphical extrapolation of data available in the literature, determined above the freezing point, led to the hypothesis that water could have a temperature of structural arrest at t0=−30 °C for H2O and −22 °C for D2O. From the present investigation of many more properties of a widely varied nature, this discovery is confirmed throughout. The method is compared with the classical logarithmic Arrhenius and van′t Hoff methods that predict t0 always to occur at 0 K, and with the more recently used power law dependence method. With the latter, extrapolated plots intersect the temperature axis at or near to a value of ts=−45 °C, that is, systematically more negative than t0. It is argued that this ts value, which is the so‐called singularity temperature, is likely to be an artefact. It is suggested that, instead of using modified van ’t Hoff or Arrhenius relationships to describe temperature dependences in the full temperature range, polynomials in (t−t0) should be used.
Synthesis of Nitrogen‐doped Carbon Nanocoils via One‐step Acetonitrile Catalytic CVD using a Ni‐Fe Layered Double Hydroxide as Catalyst Precursor
Authors: Iwasaki Tomohiro , Tomisawa Masashi , Nakamura Hideya , Watano Satoru
Published: October 2013

A simple catalytic CVD method for the synthesis of N‐doped carbon nanocoils (CNCs), using acetonitrile as both the carbon and nitrogen source, is developed. A Ni–Fe layered double hydroxide that has not been subjected to any prior annealing or reducing treatment is used as a catalyst precursor. The steps of precursor‐to‐catalyst transformation, catalyst activation, deposition of CNCs, and nitrogen doping are performed in situ, in a single process.
tert‐Butylethynyl‐parylene and Phenylethynyl‐parylene
Authors: Senkevich Jay J.
Published: October 2013

Two cross‐linkable parylene polymers, tert‐butylethynyl and phenylethynyl, were deposited via the well‐known Gorham method from a unique synthesis route to their respective cyclophane precursors. Unlike the bulky substituent group‐functionalized parylenes which exhibit low melting points (parylene E), these polymers are stable to 350 °C under vacuum because of the cross‐linking reaction which eliminates their respective melting points. This is the conversion of ethynyl groups to the diene moieties. tert‐Butylethynyl‐parylene exhibits an isotropic index of refraction, whereas phenylethynyl‐parylene is optically birefringent and has an index of refraction, much like parylene N, of 1.6595 after a 350 °C vacuum anneal. The development of cross‐linkable parylene polymers allows the improvement of both the thermo‐mechanical and optical properties of parylene. It is also very positive that the precursors can be made in a high‐yield scalable process, for example, a 60% 3‐step route for 4‐(tert‐butylethynyl)[2.2]paracyclophane.
Role of Thrombelastography (TEG) in Risk Assessment and Guidance of Antithrombotic Therapy in Patients with Coronary Artery Disease
Authors: Bitar Abbas , Kreutz Rolf P.
Published: October 2013

Clinical Development Phases I‐III Regulatory, Quality, Manufacturing

Thrombelastography (TEG) is a viscoelastic assay method used to assess whole blood and plasma coagulation kinetics. Specialized platelet mapping assays have been developed for the TEG platform to quantify the extent of platelet inhibition derived from P2Y12 receptor inhibitors, glycoprotein IIb/IIIa inhibitors, and aspirin. In this review, we describe the current evidence and summarize the data supporting the use of TEG in patients with cardiovascular disease. High thrombin‐ or adenosine diphosphate (ADP)‐induced whole blood maximal clot strength (MA) has been associated with increased risk of ischemic events after percutaneous coronary interventions (PCI) and coronary artery bypass grafting (CABG). We discuss the data linking an increased clot strength phenotype with changes in metabolic and inflammatory markers. In addition, the data supporting the role of TEG in identifying subjects at risk for hemorrhagic complications while treated with dual antiplatelet therapy or while undergoing cardiac surgery is reviewed. In summary, TEG may provide additional information combining coagulation and platelet measurements within one assay, as compared with traditional coagulation or platelet assays. Further research is warranted to establish the role of TEG in personalized medicine treatment protocols.
Analytical Detection Capabilities of Immunoassay‐Based Antiphospholipid Antibody Tests: Do They Matter?
Authors: Lakos Gabriella
Published: October 2013

Clinical Development Phases I‐III Regulatory, Quality, Manufacturing

Antiphospholipid syndrome is one of the most frequent autoimmune diseases, with approximately 1% prevalence in the general population. The syndrome is under‐recognized and underdiagnosed, and can have devastating consequences if untreated, mainly because of recurrent thrombosis. Both diagnosis and management remains challenging, but important progress has been made in the last couple of years in the detection and measurement of antiphospholipid antibodies, the hallmarks of antiphospholipid syndrome, and also in the management and treatment of the disorder. The concepts of antiphospholipid antibody profiling and risk stratification of patients have been emerging at the same time when new therapeutic approaches have become available, and new technologies are being developed or adapted to antiphospholipid antibody measurements. These methodological improvements not only support but also drive the progress that has been improving the outcome for patients with antiphospholipid syndrome.
Unsuspected allies: Chemotherapy teams up with immunity to fight cancer
Authors: Laoui Damya , Van Overmeire Eva , Van Ginderachter Jo A.
Published: October 2013

Chemotherapy has been a standard treatment for cancer for the past several decades and has long been suspected to cause systemic immune suppression. However, in recent years it has become clear that the immune status of a patient is an independent prognostic factor for chemotherapeutic efficacy, and that T‐cell‐mediated responses actively contribute to the tumor destruction triggered by some chemotherapeutic agents. In this respect, the induction of immunogenic cell death by these compounds appears to be crucial. In this issue of the European Journal of Immunology, a study by Hannesdóttir et al. [Eur. J. Immunol. 2013. 43: 2718–2729] demonstrates a crucial role for the IFN signaling molecule STAT1 during doxorubicin and Lapatinib treatment of HER2/Neu‐driven mammary carcinomas. The genotoxic anthracycline doxorubicin causes immunogenic cancer cell death and is expected to depend on the immune system, but the dual ErbB2/HER2/Neu and ErbB1/EGFR inhibitor Lapatinib also turns out to cause immune reactivity. Although CD8+ T cells are partially involved in this phenomenon, doxorubicin, and Lapatinib also affect the myeloid infiltrate (i.e. tumor‐associated macrophages and monocytes) in tumors. In this Commentary, we place these findings in the context of current knowledge and propose new avenues for future research.
Titanium Isopropoxide Promoted Tandem Self‐Cross and Ring‐Closing Metathesis Approach for the Synthesis of Macrotetralides
Authors: Muthusamy Sengodagounder , Azhagan Datshanamoorthy
Published: October 2013

A new approach is demonstrated for the synthesis of macrotetralides through an olefin metathesis reaction using Grubbs' second‐generation catalyst with titanium isopropoxide as a cocatalyst. This study demonstrates a tandem self‐cross and ring‐closing metathesis approach to form macrocyclic ring systems with excellent (E) selectivity. The reaction was optimized with regard to functional group, catalyst, solvent, Lewis acid, concentration, and temperature.
Study of Cobalt(III) Corrole as the Neutral Ionophore for Nitrite and Nitrate Detection via Polymeric Membrane Electrodes
Authors: Yang Si , Meyerhoff Mark E.
Published: October 2013

Cobalt(III) 5,10,15‐tris(4‐tert‐butylphenyl) corrole was synthesized and incorporated into plasticized poly(vinyl chloride) membranes and studied as a neutral carrier ionophore via potentiometry. This cobalt(III) complex has binding affinity to nitrite, and the resulting membrane electrode yields reversible and Nernstian response toward nitrite. Enhanced nitrite selectivity is observed over other anions, including lipophilic anions such as thiocyanate and perchlorate when an appropriate amount of lipophilic cationic sites are added to the membrane phase. Detection limit to nitrite is ca. 5 µM. Using tributylphosphate as the plasticizer with the cobalt(III) corrole species yields electrodes with enhanced nitrate selectivity.
Population genetics and forensic efficiency of twenty‐one novel microsatellite loci of Chinese Yi ethnic group
Authors: Zhu Bo‐Feng , Pan Feng , Shen Chun‐Mei , Yan Jiang‐Wei , Wang Hong‐dan , Guo Jian‐Xin , Wang Yan‐Li , Meng Hao‐Tian , Liu Wen‐Juan , Zhang Yu‐Dang , Liu Rui , Jing Hang , Xu Peng
Published: October 2013

In this study, we investigated polymorphic distributions of allelic frequencies and forensic genetic parameters of 21 novel autosomal microsatellite loci from 110 unrelated healthy individuals of Chinese Yi ethnic group. Expected heterozygosity, power of discrimination, and polymorphic information content ranged from 0.617 to 0.812, 0.777 to 0.936 and 0.560 to 0.790. The microsatellite loci showed high forensic efficiency. The total discrimination power and cumulate probability of exclusion were 0.99999999999999999986902 and 0.999998818, respectively. Locus‐by‐locus allelic frequencies were compared using analysis of molecular variance (AMOVA) method, and the statistically significant differences were observed between Yi group and Russian, Tujia, Kazak, Bai, Ningxia Han, Salar, Tibetan, and Uigur groups at 5, 6, 7, 7, 7, 8, 12, and 13 loci, respectively. The results of genetic distance comparisons, genetic structure analyses, and principal component analysis all indicated that the Yi group showed relatively short genetic relationships with Russian, Salar, and Bai group. The experimental results showed that the 21 loci in the multiplex system provided highly polymorphic information and forensic efficiency for forensic individual identification and paternity testing, also basic population data for population genetics and anthropological research.