bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biochemical, molecular characterization, and glycoproteomic analyses of α1‐proteinase inhibitor products used for replacement therapy*
Authors: Kolarich Daniel , Turecek Peter L. , Weber Alfred , Mitterer Artur , Graninger Michael , Matthiessen Peter , Nicolaes Gerry A.F. , Altmann Friedrich , Schwarz Hans Peter 
Published: October 2006

BACKGROUND: Isoelectric focusing (IEF) of α1‐proteinase inhibitor (A1PI) shows that commercial products and plasma have different glycoisoform band patterns. Those in Aralast (Grifols Biologicals) reflect an anodal shift of glycoisoforms, which has caused concern. The protein, including glycoproteomic analyses, and structural features of A1PI products were investigated by state‐of‐the‐art techniques.STUDY DESIGN AND METHODS: Batches from Aralast, Prolastin (Bayer), and Zemaira (Aventis Behring LLC) were analyzed by high‐resolution IEF and high‐performance size‐exclusion chromatography (HP‐SEC). Preparative separated isoforms from IEF were further purified by chromatography and subjected to mass spectrometry for sequence analyses, peptide mapping, and glycosylation analysis. Deamidation was quantified by enzymatic isoaspartate detection. Multiple sequence alignments and structural bioinformatics analyses were performed.RESULTS: In HP‐SEC, Prolastin had the highest aggregate content at approximately 30 percent. Isoforms from all products purified by high‐resolution IEF were sequenced with an amino acid coverage of more than 98 percent. Deamidation of Asn116 and Asn314 in A1PI was to found to some extent in all products and confirmed quantitatively by enzymatic analysis. There were no signs of methionine oxidation. Cys232 was found to be cysteinylated in A1PI in Prolastin and Aralast as in plasma, but not in Zemaira. All products showed truncation of the C‐terminal lysine. Intact A1PI concentrates contained mainly diantennary, disialylated and smaller amounts of triantennary, trisialylated N‐glycans. The percentage of fucosylation was similar in all products. Site‐specific glycan analysis revealed bands M6 contained only diantennary glycans, whereas the more acidic bands M4 and M2 also carried triantennary structures. The most acidic isoforms, M2 in Prolastin and Zemaira and M0 in Aralast, additionally exhibited tetraantennary N‐glycans.CONCLUSION: Protein chemical characterization of A1PI showed that all A1PI products to some extent differ from A1PI circulating in human plasma. Bioinformatic analysis indicated that removal of C‐terminal Lys394 and cysteinylation of Cys232 are unlikely to affect structure and/or function of A1PI but cysteinylation may influence interaction between A1PI and its physiologic ligands. Aralast, Prolastin, and Zemaira contain the same set of N‐glycans in the same ratios as those in normal human plasma A1PI. Tri‐ and tetraantennary structures are responsible for the partitioning into IEF isoforms, with the migration shift of Aralast not being due to any difference in the N‐glycosylation, but to the partial loss of the C‐terminal lysine.
Expression of the histo‐blood group B gene predominates in AB‐genotype cells
Authors: Twu Yuh‐Ching , Hsieh Chuang‐Yi , Yu Lung‐Chih 
Published: October 2006

BACKGROUND: It has been demonstrated that the 43‐bp minisatellite sequence in the 5′ region of the ABO gene plays an important role in its transcriptional regulation. It was determined in previous investigations that the structure of the minisatellite enhancer was specific to A, B, and O alleles.STUDY DESIGN AND METHODS: Real‐time polymerase chain reaction (PCR) detection and a PCR‐restriction fragment length polymorphism (RFLP) strategy were used to compare the quantities of the A and B transcripts in AB‐genotype cells, including peripheral blood cells and cancer cell line with the group AB phenotype. The 5′ 3.7‐kb regions of the A and B genes were cloned and the sequences compared. The transcriptional activities of the 5′ segments of the A and B genes were compared with luciferase reporter assay.RESULTS: Both real‐time PCR and PCR‐RFLP analyses show that there is evidently more of the B transcript in the AB‐genotype cells. It was demonstrated that the 5′ segment of the B gene had a markedly higher transcription‐activation activity relative to the A gene. This difference in transcription capability appears to result from the variation in minisatellite‐enhancer structures in the A and B genes, which contain one and four repeats of the 43‐bp enhancer unit, respectively.CONCLUSION: Our study indicates that the majority of steady‐state mRNA within AB‐genotype cells is composed of the B transcript and that this phenomenon is due to the predominant expression of the B gene relative to the A gene.
Prevalence of selected viral infections among blood donors deferred for potential risk to blood safety
Authors: Zou Shimian , Fujii Karen , Johnson Stephanie , Spencer Bryan , Washington Nicole , Iv Edward Notari , Musavi Fatemeh , Newman Bruce , Cable Ritchard , Rios Jorge , Hillyer Krista L. , Hillyer Christopher D. , Dodd Roger Y. ,   ARCNET Study Group
Published: October 2006

BACKGROUND: Health history questions identify blood donors believed to pose a higher risk of transmission of infectious diseases. This study assesses the current impact of some of these questions on blood safety as reflected by infectious disease markers.STUDY DESIGN AND METHODS: Donors who were deferred from donating blood due to health history question(s) were recruited at four different regions of the American Red Cross Blood Services. A blood sample was tested for serologic markers of blood‐borne infections as performed for accepted blood donors.RESULTS: Of 497 deferred donors enrolled, 29 donors were deferred for having had “yellow jaundice, liver disease, or hepatitis since the age of 11” (Question 3), 1 of whom had hepatitis C virus antibodies (anti‐HCV) and hepatitis B core antigen antibodies (anti‐HBc), 2 had anti‐HBc, and 1 had anti‐HCV (p < 0.05 for both markers). Among 37 donors deferred for having “ever tested positive for hepatitis” (Question 4), 1 had hepatitis B surface antigen and anti‐HBc and 3 had anti‐HBc (p < 0.05 for both markers). Of 14 donors deferred for “having ever used a needle, even once, to take any illegal or nonprescription drug” (Question 12), 1 had anti‐HCV, human T‐lymphotropic virus‐I antibodies and anti‐HBc, 1 had anti‐HCV and anti‐HBc, and 2 had anti‐HCV (p < 0.05 for all three markers).CONCLUSIONS: Blood donors deferred for standard blood donor questions regarding risk of viral hepatitis as well as those with a history of intravenous drug use were more likely to have higher hepatitis marker rates than those who were not deferred. No significant findings were identified for other markers or questions.
Continuous Quantification of Baroreflex and Respiratory Control of Heart Rate by Use of Bivariate Autoregressive Techniques
Authors: Barbieri Riccardo , Waldmann Richard A. , Di Virgilio Valerio , Triedman John K. , Bianchi Anna M. , Cerutti Sergio , Saul J. Philip 
Published: October 2006

Background:Normal cardiovascular control involves nonstationary complex interactions between a variety of variables such as heart rate (HR), arterial blood pressure (ABP), and respiratory activity.Methods:To account for both the complexity and transient nature of these phenomena, a closed‐loop bivariate and time‐variant (moving window) model was implemented using autoregressive parametric techniques to identify the typical HR and ABP spectral parameters of low frequency power (LF, 0.03–0.15 Hz), high frequency power (HF, 0.15–0.45 Hz), and their ratio LF/HF. In addition, cross‐parameters, such as the gain, phase, and coherent power, between HR, ABP, and changes in instantaneous lung volume (ILV) were computed in both the LF and HF regions.Results:The cross‐relations included the HR baroreflex (ABP‐HR, alpha), respiratory sinus arrhythmia (ILV‐HR), the mechanical influence of respiration (ILV‐ABP), and the mechanical feedforward of HR (HR‐ABP, beta). The analyses were performed on data from a gradual tilt protocol, which simulates the physiological nonstationarities encountered in daily life.Conclusions:The results were similar to those obtained using a bivariate batch (nonmoving window) Levinson‐Wiggins‐Robinson algorithm, but the time‐variant technique was able to provide nearly continuous parameters, allowing for a real‐time continuous monitoring of circulatory control.
Age and Gender Specific Criteria for Signal‐Averaged Electrocardiographic Parameters in Healthy Chinese Children
Authors: Ho Ting Fei , Yip William C.L. , Chan Kit Yee 
Published: October 2006

Background: Detection of late potentials (LPs) using signal‐averaged electrocardiograms (SAECGs) is believed to help in the prediction of malignant ventricular arrhythmias and sudden cardiac death in adults. Criteria for detection of LPs in adults may not be applicable for children, as these measurements are known to be age and sex specific.Method: SAECGs were recorded using MAC 15 ECG System. Duration of filtered QRS (TQRS), duration of high frequency, low amplitude signals in the terminal portion of QRS complex that are < 40 μV (HFLA), and root mean square voltage of the last 40 ms of the filtered QRS (RMS40) were determined for 535 healthy Chinese children, ages 6–17 years (268 males, 267 females).Results: Both mean TQRS and RMS40 were significantly different between the male and female children (TQRS: 106 ms vs 101 ms, P < 0.001; and RMS40: 62 μV vs 75 μV, P < 0.001). Mean TQRS and HFLA increased significantly with age, while mean RMS40 decreased with age (P < 0.0001). Ninetieth percentile values of TQRS and HFLA and tenth percentile value of RMS40 were used as cut‐off values for normal limits. As such, the criteria for normal TQRS, HFLA, and RMS4O were: TQRS < 117 ms; HFLA < 35 ms; and RMS40 >12 μV. Since TQRS and RMS40 were gender specific, the criteria for male and female were: TQRS: Male < 118 ms, female < 111 ms; and RMS40: Male >9 μV, female >17 μV.Conclusion: TQRS, HFLA, and RMS40 were shown to be age and sex specific in healthy Chinese children. The criteria for normal TQRS, HFLA and RMS40 were different from those proposed for adults, and this may be partly due to technical differences of the recording system.
Acceleration Spectrum Analysis: A Novel Quantitative Method for Frequenc y‐Domain Analysis of the Signal‐Averaged Electrocardiogram
Authors: Chan Eric K.Y. 
Published: October 2006

Background: Frequency‐domain techniques presently used for micropotential analysis in the signal averaged ECG (SAECC) have several inherent shortcomings. For example, they depend on sensitive determination of the I‐point, which becomes inaccurate in the presence of noise, or derivation of multiple, complicated statistical parameters to quantify spectral characteristics in a three‐dimensional “spectral temporal map.” While these techniques are not as well accepted clinically as the conventional time‐domain Simson method, the latter is not without limitations either. Although time‐domain SAECG analysis has a very high negative predictive value, it has low positive predictive accuracy. Furthermore, it cannot be used to analyze SAECC data in patients with conduction delay problems, such as bundle branch block. Hence, the goal of this new frequency‐domain technique is to address and solve some of these shortcomings.Methods: The Fourier transform of the second derivative signal, or “acceleration spectrum,” extracts the frequency‐domain “signature” of damaged myocardium throughout the entire QRS complex, rather than from only the late potential region. The technique i s not dependent on precise endpoint or other fiducial point determination. A “spectral change index” (SCI) for quantifying variation from 50‐300 Hz in the acceleration spectrum i s calculated. The characterization of the cut‐off values for the SCI was based on results from a study including 50 postmyocardial infarction (post‐MI) patients (25 of whom were inducible to sustained ventricular tachycardia), and 10 normal controls.Results: An SCI <20, typical of a normal, “flat” acceleration spectrum in the 50‐ to 300‐Hz band width, may indicate undamaged myocardium, while an SCI 220 corresponding to a higher degree of spectral “fragmentation” in the same bandwidth, may indicate increased myocardial tissue damage. Using this cutoff, the sensitivity, specificity, and positive and negative predictive values for this initial study were 72%, 84%, 82%, and 75%, respectively.Conclusions: Acceleration spectrum analysis (ASA) using the SCI shows promise in predicting inducibility in post‐MI patients, including those with conduction delay problems. Since it is well documented that time‐domain SAECG has a high negative predictive value and a low positive predictive value, the high positive predictive value of the newly developed ASA increases the overall value of the SAECG test.
Comparison of QT/RR Relationship Using Two Algorithms of QT Interval Analysis for Identification of High Risk Patients for Life‐Threatening Ventricular Arrhythmias
Authors: Kiuge Petra , Walter Thomas , Neugebauer Annerose 
Published: October 2006

Objective: The purpose of this study was to evaluate the dynamic relationship between QT and RR intervals considering either the QTe interval (i.e., time between the onset of QRS and the end of the T wave) or the QTa interval (i.e., time between the onset of QRS and the apex of the T wave) from 30‐second modules.Method: The Holter recordings in three groups of adult subjects (30 patients with malignant ventricular tachyarrhythmias [VT/VF patients], 40 patients with coronary artery disease [CAD], and 44 normal subjects) were analyzed using the ELATEC System.Results: In normal subjects the correlation coefficient between QTa and RR (QTa/RR) was significantly higher (0.87 ± 0.12) than those between QTe and RR (QTe/RR) (0.79 ± 0.17). In the other groups there was no significant difference between QTa/RR and QTe/RR: QTa/RR (CAD: 0.71 ± 0.3; VT/VF: 0.73 ± 0.19); and QTe/RR (CAD: 0.63 ± 0.33; VT/VF: 0.69 ± 0.21). The slope of QTe/ RR over 24 hours was significantly larger in VT/VF patients (0.23 ± 0.11) than in the other groups (control: 0.18 ± 0.08; CAD: 0.17 ± 0.1). Measuring the QTa/RR relation there was no difference between the three groups (VT/VF: 0.19 ± 0.09; CAD: 0.15 ± 0.09; normal: 0.19 ± 0.06).Conclusion: QTe/RR as well as QTa/RR analyses are methods of detecting a deranged rate dependence of QT intervals in high risk patients. An increased QTe/RR slope indicates a higher risk of life‐threatening ventricular arrhythmias. Because there was no difference in QTa/RR we conclude that the end of the T wave gives important information about disorders in repolarization.
Continuous QT Interval Measurements from 24‐Hour Electrocardiography and Risk after Myocardial Infarction
Authors: Brüggemann Thomas , Eisenreich Sven , Behrens Steffen , Ehlers Christoph , Muller Dirk , Andresen Dietrich 
Published: October 2006

Objectives: The aim of this study was to examine the clinical value of QT analysis from Holter recordings in patients after myocardial infarction (Ml).Background: Prolongation and dispersion of QT intervals in the 12‐lead standard ECG have been proposed as indicators of risk for arrhythmic events. However, the value of QT and T wave measurements from Holter recordings has yet to be established.Methods: Intervals from Q to the peak and to the end of T were determined every 30 seconds from 24‐hour Holter recordings and corrected for cycle length (QTc). The duration of late repolarization was calculated as QT end minus QT peak. 24‐hour QT variability was determined as the standard error of estimate from the linear regression analysis of QT and RR intervals. In a case control design, 51 post‐MI patients suffering from subsequent cardiac death within 1 year were compared to 51 post‐MI patients with an uncomplicated follow‐up.Results: QTc intervals as well as 24‐hour QT variability did not differ between post‐MI patients with favorable and unfavorable clinical outcome. However, there was a prolonged interval from the peak to the end of the T wave in cardiac death victims (mean ± SE: 110 ± 4 ms) as compared to controls (95 ± 3ms, P < 0.001).Conclusions: Prolongation of the late repolarization phase seems to be associated with an increased risk of cardiac death after Ml. Standard QT measurements from ambulatory ECG recordings have no predictive value in post‐MI patients.
Gene‐Specific Therapy for Long QT Syndrome
Authors: Rosero Spencer Z. , Zareba Wojciech , Robinson Jennifer L. , Moss Arthur J. 
Published: October 2006

Background: One form of the hereditary long QT syndrome (LQT‐3) has recently been shown to be caused by the SCN5A mutation of the human cardiac sodium channel. Cellular studies have suggested that type lb antiarrhythmics may be potentially therapeutic via preferential blockade of the resulting abnormal late inward sodium current. To test this hypothesis, we implemented a pilot study to evaluate the potential for long‐term, gene‐specific therapy in patients with this disease.Methods and Results: The effects of short‐term intravenous lidocaine and oral tocainide were studied in three siblings: two carriers of the SCN5A mutation; and one noncarrier. The two carriers had prolonged QT intervals at baseline, 531 ms, and 566 ms, which markedly shortened with intravenous lidocaine to 438 and 482 ms, respectively. Tocainide‐induced correction of the QT interval was similar in both carriers. The noncarrier did not have any significant change in the QT with either drug. One carrier was then placed on outpatient therapy with oral tocainide, and has demonstrated persistent normalization of the QT interval and T wave morphology during the past 10 months.Conclusion: This is the first demonstration of long‐term outpatient treatment in LQT‐3 using oral tocainide during a 10‐month period. QT shortening was achieved by both intravenous lidocaine and oral tocainide, with no adverse affects. The predominant effect was a reduction in the QT onset interval, suggesting that blockade of the mutant sodium current allows repolarization to begin at an earlier time during the action potential.
Reproducibility of QT Interval Measurements Obtained from 24‐Hour Digitized Ambulatory Three‐Lead Electrocardiograms in Patients with Acute Myocardial Infarction and Healthy Volunteers
Authors: Copie Xavier , Alonso Christine , Lavergne Thomas , Iliou Marie‐Christine , Guize Louis , Le Heuzey Jean‐Yves 
Published: October 2006

BackgroundChanges in QT interval durations on 24‐hour ambulatory ECGs reflect circadian variations in ventricular repolarization. However, the reproducibility of such measurements is unknown.MethodsTwo 24‐hour Holter recordings were obtained in 9 healthy volunteers, and in 15 post‐myocardial infarction (Ml) patients. First, automated measurements of QT apex and QT end were compared with manual measurements. Second, automated measurements of QT intervals were compared for each subject between the first and second Holter recordings. The coefficient of reproducibility was calculated as twice the standard deviation of differences between paired measurements.ResultsThe coefficient of reproducibility for the comparison of manual and automated measurements of QT apex was 9 ms in healthy volunteers and 12 ms in post‐MI patients. This coefficient was 12 ms in both healthy volunteers and post‐MI patients for the comparison of manual and automated measurements of QT end. The coefficient of reproducibility for the comparison of automated measures of QT apex in the two Holter recordings was 16 ms in healthy volunteers and 18 ms in post‐MI patients. These coefficients were 19 ms and 23 ms, respectively, for the comparison of automated measures of QT end.ConclusionsAutomated and manual measurements of QT intervals obtained from 24‐hour ambulatory ECGs provide similar results. Short‐term reproducibility of automated measurements of QT intervals is acceptable.
Tilt‐Table Testing in Syncopal Patients with Sick Sinus Syndrome: A Guide to Pathophysiology and Management?
Authors: Gatzoulis Kostas A. , Mamarelis Ioannis I. , Theopistou Artemis M. , Sideris Skevos K. , Avgeropoulou Katerina , Gialafos John H. , Toutouzas Pavlos K. 
Published: October 2006

BackgroundA possible role of a neurally mediated component in the syncope mechanism of patients with sick sinus syndrome has not been adequately evaluated.MethodsWe examined and compared three groups: group 1, 25 syncopal patients (age 55 ± 15, M/F 18/7, syncope attacks per patient 6 ± 7) with sick sinus syndrome (persistent unexplained bradycardia with a long sinus pause and/or a long sinus node recovery time, a long sinoatrial conduction time, a low intrinsic heart rate, and/or an incompetent chronotropic response to atropine); group 2: 45 patients (age 43 ± 18, M/F 28/17, syncope attacks per patient 6 ± 7) with syncope of unknown etiology; group 3:20 healthy controls (age 34 ± 9, M/F 16/4). The tilt‐table test protocol used consisted of an initial 20‐minute period at 80° tilt followed by three 10‐minute periods in the same position under graded isoproterenol intravenous infusion at 1–3 μ;g/min. The test was considered positive if presyncope or syncope due to hypotension and/or bradycardia was induced.ResultsA similar proportion of group 1 and group 2 patients developed a positive test (12 or 48% and 25 or 56%, respectively, P:NS) with a similar positive tilt‐table test duration in both groups (41 ± 22 vs 43 ± 17 minutes, P:NS). In contrast, only four of the group 3 healthy controls (20%) developed a positive test with a much longer test duration (P < 0.005).ConclusionsSyncopal patients with sick sinus syndrome commonly exhibit a neurally mediated syncope reaction during a tilt‐table test. This might explain the occasional failure to prevent recurrent syncope in sick sinus syndrome patients treated with cardiac pacing. Concurrent β‐blocker therapy may be indicated for such patients.
QT Dispersion: Comparison of Orthogonal, Quasi‐orthogonal, and 12‐Lead Configurations
Authors: Beuve Claude Sainte , Badilini Fabio , Blanche Pierre Maison , Kedra Antoni , Coumel Philippe 
Published: October 2006

BackgroundFull standardization of QT dispersion has not yet been established; the influence of lead combination is still disputed. This study evaluates the respective value of automated QTc dispersion in orthogonal (XYZ), quasi‐orthogonal I‐aVF‐V2 (IF2), and 12‐lead ECG configurations.Methods15‐lead digitized ECG recordings were collected in 92 normal subjects and in 71 patients following myocardial infarction. Each lead was processed by an automatic algorithm. QT dispersion was assessed by the range of individual QT intervals, both corrected by Bazett's formula. QTc durations from all configurations were comparable (post‐MI: 412 ± 27 vs 407 ± 29 msec for 12‐lead and XYZ). Whatever the set of leads, QTc interval was longer in post‐MI (in 12‐lead, 412 ± 27 vs 397 ± 19 ms in normals, P < 0.001). QTc dispersion was larger on 12‐lead (post‐MI: 51 ± 19, 21 ± 13 and 28 ± 20 ms with 12‐lead, XYZ and IF2); however, it was significantly larger in post‐MI with all sets of leads (in XYZ, 21 ± 13 vs 9 ± 7 ms in normal subjects, P < 0.0001).ConclusionIn conclusion, magnitude of QT dispersion depends on the set of leads considered; orthogonal configurations may still contain valuable prognostic information.