Optimal high-pass filter settings of the signal-averaged electrocardiogram in patients with arrhythmogenic right ventricular dysplasia.
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Adult↗
Biomedical subjects
R Frank
Publications and source records attributed to R Frank.
Endothelin-1 in patients with coronary heart disease undergoing cardiac catheterization.
OBJECTIVES: This study examined the possible association between endothelin and coronary atherosclerosis and evaluated the synthesis and release of endothelin in the presence of various stimuli that occur during cardiac catheterization. BACKGROUND: Circulating endothelin has been reported to be increased in diffuse atherosclerosis and acute myocardial infarction. However, the relation between coronary artery disease and endothelin release remains unclear. METHODS: We measured the plasma and urinary concentrations of endothelin immunoreactivity in 45 patients and 10 healthy control subjects. RESULTS: In group IA (n = 9), simultaneous blood sampling in the coronary sinus and femoral artery during coronary angioplasty of the left anterior descending coronary artery demonstrated no immediate changes in plasma immunoreactive endothelin-1 (ir-ET-1) levels. In 11 patients in group IB undergoing coronary angioplasty of a major artery, we did not detect changes in peripheral plasma concentrations of ir-ET-1 within 24 h, but urinary ir-ET-1 levels increased from 9.2 +/- 2.3 to 18.6 +/- 4.9 pg/mg of creatinine a few hours after coronary angioplasty (mean +/- SEM, p < 0.05). This increase in urinary endothelin excretion persisted 24 h later. Group II patients (n = 12) had coronary angiography without coronary angioplasty. Levels of both plasma and urinary ir-ET-1 did not change during the 24-h follow-up period. There was no relation between the severity of coronary atherosclerosis and the plasma or urinary concentrations of ir-ET-1. Systolic aortic pressure correlated with basal urinary excretion of endothelin (r = 0.54, p = 0.03, n = 15). In group III (n = 13), levels of ir-ET-1 in patients undergoing right heart catheterization without angiography did not differ from those in the control group. CONCLUSIONS: The presence or the severity, or both, of coronary atherosclerosis is not associated with a detectable increase in endothelin release. The diagnostic procedures of catheterization do not modify endothelin concentrations in plasma and urine. Vascular stretch or injury, or both, during coronary angioplasty increases urinary ir-ET-1 levels a few hours after the procedure. This increase persists for at least 24 h but is not detectable by brief sampling of peripheral or coronary sinus blood.
Angioplasty, Balloon, Coronary↗
T cell epitope analysis with peptides simultaneously synthesized on cellulose membranes: fine mapping of two DQ dependent epitopes.
Several MHC class II restricted, CD4+ human T cell clones from three donors were induced with soluble matrix protein of influenza virus. The epitopes recognized by these clones were mapped using a complete set of overlapping 15-mer peptides synthesized with the newly developed SPOT method which allows the simple simultaneous synthesis of numerous peptides on cellulose membranes. Fine analysis of two clones by truncation of the stimulatory peptide by single subsequent amino acids from either the NH2- or the COOH-terminus revealed the minimal stimulatory determinants of two DQ dependent T cell epitopes.
Amino Acid Sequence↗
Structure of the equine infectious anemia virus Tat protein.
Trans-activator (Tat) proteins regulate the transcription of lentiviral DNA in the host cell genome. These RNA binding proteins participate in the life cycle of all known lentiviruses, such as the human immunodeficiency viruses (HIV) or the equine infectious anemia virus (EIAV). The consensus RNA binding motifs [the trans-activation responsive element (TAR)] of HIV-1 as well as EIAV Tat proteins are well characterized. The structure of the 75-amino acid EIAV Tat protein in solution was determined by two- and three-dimensional nuclear magnetic resonance methods and molecular dynamics calculations. The protein structure exhibits a well-defined hydrophobic core of 15 amino acids that serves as a scaffold for two flexible domains corresponding to the NH2- and COOH-terminal regions. The core region is a strictly conserved sequence region among the known Tat proteins. The structural data can be used to explain several of the observed features of Tat proteins.
Amino Acid Sequence↗
Purification of a novel G-protein alpha 0-subtype from mammalian brain.
Three distinct G-protein alpha o-subtypes, i.e. alpha o1, alpha o2 and a newly observed 'alpha o3', are present in membranes of mammalian brain, each appearing as two isoforms on SDS/PAGE. Only alpha o1 and alpha o2 appear to be substrates for pertussis toxin (PTX) when membranes or partially purified proteins are examined. In order to elucidate the apparent PTX-resistance of the third alpha o-subtype, we purified alpha o3 from porcine and bovine brain membranes. During the purification procedures, alpha o3 occurred in its dissociated monomeric form and, together with beta gamma-complexes, as a heterotrimer. In a first attempt, we used purified G-protein alpha i/alpha o-mixtures to obtain a final separation of alpha o3. By using f.p.l.c. anion-exchange chromatography on a Mono Q column, complete separation of alpha i1 and alpha o2 was achieved. Partial resolution of alpha o1, alpha i2 and alpha o3 was observed; alpha o3 was eluted between alpha o1 and alpha i2. If alpha o-subunits free from alpha i contaminants were loaded on to the Mono Q column, all three alpha o-subtypes were resolved. The identity of the third subtype as an alpha o-subtype was confirmed by sequence analysis of tryptic fragments. All three alpha o-subtypes bound GTP[S]. Purified alpha o3 was ADP-ribosylated when subjected to PTX treatment in the presence of beta gamma-subunits, and on SDS/PAGE the mobility of alpha o3 was similar to that of ADP-ribosylated alpha o1. On the basis of results obtained with subtype-specific antibodies, the third alpha o-subtype is immunologically more related to alpha o1 than to alpha o2. Purified alpha o3 failed to reconstitute carbachol-mediated inhibition of Ca2+ current in PTX-pretreated SH-SY5Y-cells, whereas alpha o1 and alpha o2 did successfully restore this effect. We conclude that the novel alpha o3 forms differs from alpha o1 and alpha o2 in its primary structure and may be involved in signal-transduction pathways other than those described for alpha o1 and alpha o2.
Adenosine Diphosphate Ribose↗
The return of Phineas Gage: clues about the brain from the skull of a famous patient.
When the landmark patient Phineas Gage died in 1861, no autopsy was performed, but his skull was later recovered. The brain lesion that caused the profound personality changes for which his case became famous has been presumed to have involved the left frontal region, but questions have been raised about the involvement of other regions and about the exact placement of the lesion within the vast frontal territory. Measurements from Gage's skull and modern neuroimaging techniques were used to reconstitute the accident and determine the probable location of the lesion. The damage involved both left and right prefrontal cortices in a pattern that, as confirmed by Gage's modern counterparts, causes a defect in rational decision making and the processing of emotion.
Accidents, Occupational↗
Molecular cloning and expression of a novel type V adenylyl cyclase from rabbit myocardium.
A cDNA of a novel form of type V adenylyl cyclase has been cloned from rabbit myocardium using oligonucleotide probes derived from peptides that were produced by enzymatic cleavage of purified heart cyclase. A corresponding mRNA (6 kb) has been detected in rabbit myocardial tissue by Northern blot analysis. The cDNA encodes a protein of 1,264 amino acids exhibiting 12 putative membrane-spanning regions in its hydrophilicity profile. Sequence comparison to two other previously published type V adenylyl cyclase reveals amino-terminal domains of different length and low correlative homology, whereas the rest of the sequences is almost identical. The nonconserved amino-terminal region of the subtype consists of 214 amino acids and exceeds the length of the others by 40 and 80 residues, respectively. Its presence in membrane preparations from different tissues has been confirmed immunologically using an antibody directed against a synthetic peptide. The cloned adenylyl cyclase was functionally expressed in COS-1 cells to attain an enzymatic activity 3.5- to 14-fold above control in the presence of forskolin.
Adenylyl Cyclases↗
Interaction of phlorizin, a potent inhibitor of the Na+/D-glucose cotransporter, with the NADPH-binding site of mammalian catalases.
Phlorizin is a reversible inhibitor of the renal and small intestinal Na+/D-glucose cotransporter. In an attempt to purify the Na+/D-glucose cotransporter from a pig kidney brush border membrane fraction, we used an Affi-Gel affinity chromatography column to which 3-aminophlorizin had been coupled. A protein, composed according to crosslinking experiments of at least 3 subunits of molecular weight 60 kDa, was found to bind specifically to the phlorizin column. This protein was subsequently identified as catalase by sequence homology of three of its tryptic fragments to the sequence of several mammalian catalases as well as by its enzymatic activity. Although bovine liver catalase was bound tightly to the affinity matrix, phlorizin had no effect on the ability of the enzyme to degrade H2O2. In contrast, the Aspergillus niger and Neurospora crassa catalases did not bind to the phlorizin column. This difference may be related to the fact that mammalian catalases, but not the fungal catalases, contain an NADPH binding site with a yet unknown function. Interestingly, bovine liver catalase could be eluted with 50 microM NADPH from phlorizin columns. Irradiation in the presence of [3H]4-azidophlorizin allowed photolabeling of bovine liver catalase, which was prevented by the presence of 10 microM NADPH. After digestion of photolabeled catalase with chymotrypsin, a radioactive peptide was detected that was absent in catalase protected with NADPH. Docking simulations suggested that phlorizin can bind to the NADPH binding site with high affinity.
Amino Acid Sequence↗
Location, size, and complexity of epitopes on the coat protein of beet necrotic yellow vein virus studied by means of synthetic overlapping peptides.
Five regions on the coat protein of BNYVV which had been shown previously to be involved in the formation of continuous epitopes were further analyzed by means of synthetic overlapping peptides. It was found that at least some of these regions may encompass several overlapping epitopes (or parts thereof). Four monoclonal antibodies (MAbs) which were known to be specific for the C-terminus of BNYVV coat protein (amino acids 182-188 = RTSPPGQ) were found to react with different sets of peptides which had either the sequence RTS, RTSP, RTSPP, or PPGQ in common. Two other MAbs which also had been shown previously to be specific for the C-terminus of BNYVV coat protein failed to react with overlapping decapeptides. Two epitopes which were previously located in the areas of amino acids 115-125 and 125-140 could now be located more precisely on the sequences SANVRRD (amino acids 115-121) and AESSG (amino acids 128-132), respectively. Replacement studies with alanine showed that not all amino acids within these sequences are equally important for antibody binding. On the other hand, amino acids outside these sequences may strongly influence the reactivity of epitopes. The accessibility of amino acid sequences on the particles of BNYVV is discussed.
Amino Acid Sequence↗
Diagnosis of ventricular tachycardia using a pacemaker Holter function.
The diagnosis of ventricular tachycardia (VT) using the Holter function of an implanted pacemaker has not yet been reported. We present the case of a patient with episodes of slow VT, hemodynamically stable, but in whom long lasting attacks were not identified by the patient as VT recurrences, finally leading to progressive heart failure. Prospective analysis of the 24-hour ECG and comparison with the pacemaker Holter data allowed us to determine diagnostic criteria to recognize VT using the pacemaker Holter function. Using these criteria it was possible to retrospectively diagnose VT occurrence during the weeks when the patient was out-of-hospital.
Aged↗
Synthetic peptides derived from the Listeria monocytogenes p60 protein as antigens for the generation of polyclonal antibodies specific for secreted cell-free L. monocytogenes p60 proteins.
All species of the genus Listeria secrete a major extracellular protein called p60. A comparison of the deduced amino acid sequences of all listerial p60 proteins previously indicated there were only a few regions which were unique to the pathogenic, food-borne species Listeria monocytogenes. Two of these p60 regions were chosen for the development of antibodies specific for the facultative intracellular species L. monocytogenes. Initially, these regions were characterized via epitope mapping, and this led to the development of two different synthetic peptides. Rabbits immunized with these synthetic peptides generated polyclonal antibodies that were then used in Western blot (immunoblot) analyses. Antiserum against peptide A (PepA) recognized the p60 protein in the supernatants collected from most L. monocytogenes serotypes except for several strains belonging to serotypes 4a and 4c. No p60-related protein was detected in the supernatants from other Listeria species with this anti-PepA antiserum. Antibodies raised against peptide D (PepD) reacted with p60 from all L. monocytogenes serotypes, including all 4a and 4c strains that were tested, and also showed no cross-reactivity with supernatant proteins from other Listeria species. Both antisera also detected p60 in supernatants of a large number of environmental isolates of L. monocytogenes. Besides Western blot analyses, these antisera to PepA and PepD reacted with secreted p60 in an enzyme-linked immunosorbent assay, indicating recognition of the native antigen in addition to the denatured form. These data suggest that synthetic peptides derived from the variable region of the L. monocytogenes p60 protein may be useful for the development of an immunological diagnostic assay.
Amino Acid Sequence↗
[Value and limitations of diagnostic function of bradycardia of a ventricular pacemaker].
The indication for permanent pacing may be confirmed by a bradycardia counter in patients without ECG or Holter recording of the causal bradycardia. The algorithm was assessed in a multicenter register with the SORIN Theorema model. The activation of the device was programmed on a double hysteresis of 2 seconds with a programmable histogramme of detections and sensing and pacing counters. One hundred and forty five patients were recruited in 50 centers over 2 years: 89 men and 56 women aged 33 to 96 years (average 72 years), 87 of whom had no other obvious cardiac disease. One hundred and ten had typical syncopal episodes, 19 had atypical or minor syncopal attacks and 16 were asymptomatic, one with sinus node dysfunction and the others with pathological prolongation of the HV interval (> or = 70 ms) during endocavitary electrophysiological investigation. The mechanism of the bradycardia was considered to be infra-hisian in 62 patients who had HV intervals > or = 70 ms. This was also the probable mechanism in 20 others who had bundle branch block and typical syncope despite a HV interval < 70 ms and in 6 patients with bundle branch block and typical syncope who did not undergo electrophysiological investigation before implantation. Twenty one patients had sinus node dysfunction during electrophysiological investigation and 8 had a carotid sinus syndrome. The remaining 28 cases had transient syncope but no ECG changes or abnormality on electrophysiological investigation. Permanent pacing was proposed when an extracardiac origin of the syncope was excluded.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Fulguration and radiofrequency in ventricular tachycardia].
Eighty-nine cases of ventricular tachycardia, resistant to antiarrhythmic therapy, were treated over a 10 year period by high energy D ablation (fulguration). This series included 37 cases of myocardial infarction with a mean ejection fraction of 30%. The mean follow-up period of the survivors was 61 months and clinical efficacy was 87.9%. Twenty-three cases of arrhythmogenic right ventricular dysplasia, aged 40 years, and with an ejection fraction of 57%, followed up for 71 months, had a clinical efficacy of 83%. Twelve patients had verapamil sensitive (fascicular) ventricular tachycardia. Their age was 30, their ejection fraction 65%, the follow-up period 55 months, and the clinical efficacy was 100%. Ten patients had primary dilated cardiomyopathy. Their age was 35, their ejection fraction 23%, the follow-up period of 38 months with a clinical efficacy of 80%. Four patients, aged 21, had operated congenital heart disease with an ejection fraction of 60%, a follow-up of 36 months and a clinical efficacy of 100%. Finally, 3 patients had idiopathic infundibular ventricular tachycardia. Their age was 36, the ejection fraction 62%, the follow-up period was 72 months and the clinical efficacy was 67%. Non lethal complications were observed in 16% of cases, mainly haemopericardium requiring pericardocentesis in 4.5% of cases. The operative mortality and in the month following ablation was 9.2%, observed mainly during the learning period. These results show that fulguration is not without risk, but in skilled hands, it gives remarkable results in the majority of cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[Ablative methods, therapeutic alternative to medical treatment for junctional tachycardia].
The clinical syndrome corresponding to junctional tachycardia is generally known as Bouveret's disease, but actually corresponds to two quite separate entities: 1) tachycardia related to a secondary atrioventricular pathway or Kent bundle; 2) intranodal tachycardia arising in the atrio-ventricular node. Until recently, anti-arrhythmics were used to treat most of the cases of accessory pathways. If this was unsuccessful or if the anti-arrhythmics induced adverse effects and in life-threatening cases affecting Kent bundles, surgical section was sometimes proposed, carrying a non-negligible risk of morbidity and mortality. Intranodal arrhythmia is not a serious, but may call for prophylactic antiarrhythmic treatment if it becomes too frequent and disabling. Before the advent of ablative treatment, there was no satisfactory alternative to antiarrhythmic treatment. Ablation of the accessory pathways or selection ablation of the slow pathway of the atrio-ventricular node (sometimes of the rapid pathway) is not achieved by applying a high-frequency current (radiofrequency), which has virtually replaced fulguration (destruction using a modified electrical current). In both types of tachycardia, a cure is obtained in 90% of cases with a low incidence of complications and virtually no risk of mortality, which contrasts favorably with long-term antiarrhythmic treatment (or surgical section of Kent bundles), which justifies the large-scale development of radiofrequency ablation.
Catheter Ablation↗
[Bayesian approach to electrocardiographic criteria in arrhythmogenic right ventricular dysplasia].
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Arrhythmias, Cardiac↗
[Repolarization and intraventricular conduction disorders in arrhythmogenic right ventricular dysplasia].
Right ventricular dysplasia may lead to sudden cardiac death an adolescent or adult with little or no symptoms. Identification of this condition in the high-risk population appears to be an objective to be attained in the near future. Thorough ECG analysis seems to be a non-invasive and inexpensive technique which could be used as a first approach for screening of the disorder. In a series of 50 cases of arrhythmogenic right ventricular dysplasia compared with a control group, the diagnosis of ARVD could be determined by ECG with 84% sensitivity and 100% specificity if QRS duration in leads V1, V2 or V3 was longer than 110 ms, T wave was negative in V2 or if T wave was negative in V1, but in this latter case only provided incomplete right bundle branch block was present.
Adolescent↗
Equine infectious anemia virus Tat is a predominantly helical protein.
Nuclear magnetic resonance (NMR) spectroscopy revealed features of the secondary structure of the equine infectious anemia virus (EIAV) Tat protein in solution. We could show that this protein, which is required in the replication cycle of lentiviruses, forms a predominantly helical structure in trifluoroethanol/water (40% by vol.) solution. In particular, the basic RNA-binding region and the adjacent core domain, which are highly conserved among lentiviral Tat proteins, show helix-type secondary structure under these conditions. Our observations, in concert with recent biochemical data from other laboratories, suggest that the core sequence region and the basic sequence region form interdependent structural domains, both possibly necessary for correct RNA binding.
Amino Acid Sequence↗
Sequence-specific resonance assignments of the 1H-NMR spectra of a synthetic, biologically active EIAV Tat protein.
The equine infectious anemia virus (EIAV) trans-activating (Tat) protein is a close homologue of the human immunodeficiency virus (HIV) Tat protein. Both of these proteins bind to an RNA trans-activation responsive element (TAR). We synthesized chemically a protein with the sequence of the 75 amino acid Tat protein from EIAV. The chemically synthesized protein was shown to be biologically active. Circular dichroism (CD) and 1H nuclear magnetic resonance (NMR) spectroscopy were used to structurally characterize the synthetic protein. We obtained nearly complete resonance assignments in the 2D-NMR spectra of the protein at pH 3.0. There is at least some evidence from the experimental data that the basic TAR binding domain of the synthetic protein has a tendency to form a helix, but our experiments also indicate that the protein probably does not have an overall stable tertiary structure in aqueous solution at this pH. CD spectroscopy suggested that the protein adopts a more stable, predominantly alpha-helical structure in a trifluoroethanol/water solution.
Amino Acid Sequence↗