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Biomedical subjects

Alexander Mazur

Publications and source records attributed to Alexander Mazur.

15 recordsLinked to original sources
PubMed2006

Integrity of the Mod(mdg4)-67.2 BTB domain is critical to insulator function in Drosophila melanogaster.

The Drosophila gypsy insulator contains binding sites for the Suppressor of Hairy-wing [Su(Hw)] protein. Enhancer and silencer blocking require Su(Hw) recruitment of Mod(mdg4)-67.2, a BTB/POZ domain protein that interacts with Su(Hw) through a carboxyl-terminal acidic domain. Here we conducted mutational analyses of the Mod(mdg4)-67.2 BTB domain. We demonstrate that this domain is essential for insulator function, in part through direction of protein dimerization. Our studies revealed the presence of a second domain (DD) that contributes to Mod(mdg4)-67.2 dimerization when the function of the BTB domain is compromised. Additionally, we demonstrate that mutations in amino acids of the charged pocket in the BTB domain that retain dimerization of the mutated protein cause a loss of insulator function. In these cases, the mutant proteins failed to localize to chromosomes, suggesting a role for the BTB domain in chromosome association. Interestingly, replacement of the Mod(mdg4)-67.2 BTB domain with the GAF BTB domain produced a nonfunctional protein. Taken together, these data suggest that the Mod(mdg4)-67.2 BTB domain confers novel activities to gypsy insulator function.

Alleles↗
PubMed2006

Urgent cardiac resynchronization therapy in patients with decompensated chronic heart failure receiving inotropic therapy. A case series.

BACKGROUND: It remains unknown whether patients with severe decompensated class IV heart failure (HF) receiving intravenous inotropic treatment benefit from cardiac resynchronization therapy (CRT). METHODS: We identified patients who underwent urgent CRT implantation due to decompensated class IV HF necessitating intravenous inotropic therapy. RESULTS: Of 10 patients with chronic ischemic cardiomyopathy (median QRS duration of 170 ms), CRT implantation was associated with symptomatic improvement in 8 patients. The mortality rate was 50% during a median follow-up of 9.5 months, with a median CRT-to-death duration of 6 months. CONCLUSIONS: CRT was feasible among class IV patients receiving inotropic treatment and was associated with clinical improvement.

Aged↗
PubMed2005

An acetylated 120-kDa lysosomal transmembrane protein is absent from mucopolysaccharidosis IIIC fibroblasts: a candidate molecule for MPS IIIC.

Genetic deficiency of the lysosomal enzyme, acetyl-CoA: alpha-glucosaminide N-acetyltransferase (N-acetyltransferase), which catalyses the transmembrane acetylation of heparan sulfate results in severe neurodegenerative disease, mucopolysaccharidosis IIIC. N-Acetyltransferase has never been characterized structurally and its gene has never been identified. We combined traditional methods of enzyme purification with organellar proteomics, isolating lysosomal membranes from mouse liver using differential centrifugation and osmolysis, followed by detergent extraction and purification of N-acetyltransferase by liquid chromatography. Partially purified enzyme had a molecular mass of 240 kDa and pI of 7.4 by gel filtration and chromatofocusing. Its specific activity varied with protein concentration typical of oligomeric enzymes or multienzyme complexes. Incubation of N-acetyltransferase with acetyl[14C]CoA in the absence of the acceptor of the acetyl group resulted in radioactive labeling of a 120-kDa polypeptide, suggesting that it represents a subunit containing the enzyme active site. Furthermore, following acetyl[14C]-labeling, the 120-kDa protein was present in the lysosomal membranes purified from the normal human skin fibroblasts but absent in those from the skin fibroblasts of MPS IIIC patients.

Acetyl Coenzyme A↗
PubMed2005

Bundle branch reentrant ventricular tachycardia.

Bundle branch reentrant (BBR) tachycardia is an uncommon form of ventricular tachycardia (VT) incorporating both bundle branches into the reentry circuit. The arrhythmia is usually seen in patients with an acquired heart disease and significant conduction system impairment, although patients with structurally normal heart have been described. Surface ECG in sinus rhythm (SR) characteristically shows intraventricular conduction defects. Patients typically present with presyncope, syncope or sudden death because of VT with fast rates frequently above 200 beats per minute. The QRS morphology during VT is a typical bundle branch block pattern, usually left bundle branch block, and may be identical to that in SR. Prolonged His-ventricular (H-V) interval in SR is found in the majority of patients with BBR VT, although some patients may have the H-V interval within normal limits. The diagnosis of BBR VT is based on electrophysiological findings and pacing maneuvers that prove participation of the His- Purkinje system in the tachycardia mechanism. Radiofrequency catheter ablation of a bundle branch can cure BBR VT and is currently regarded as the first line therapy. The technique of choice is ablation of the right bundle. The reported incidence of clinically significant conduction system impairment requiring implantation of a permanent pacemaker varies from 0% to 30%. Long-term outcome depends on the underlying cardiac disease. Patients with poor systolic left ventricular function are at risk of sudden death or death from progressive heart failure despite successful BBR VT ablation and should be considered for an implantable cardiovertor-defibrillator.

Journal Article↗
PubMed2005

Atrial flutter after surgical radiofrequency ablation of the left atrium for atrial fibrillation.

BACKGROUND: Left atrial radiofrequency ablation is the most common technique for the treatment of atrial fibrillation during mitral valve surgery. Reported failure rates range between 15% and 30%, with some patients remaining in atrial fibrillation and others experiencing atrial flutter. The incidence and nature of the postoperative atrial flutter is not yet well defined. METHODS: The study group consisted of 50 patients with atrial fibrillation who underwent mitral valve surgery combined with left atrial radiofrequency ablation, and were followed for a mean period of 15 +/- 7 months. The majority of patients (39; 78%) had persistent or permanent atrial fibrillation. Placement of the ablation lines was as follows: encircling the pulmonary veins, isolating the base of the left atrial appendage, and bridging the lateral or posterior mitral annulus and the margin of the pulmonary vein or the appendage-encircling ablation lines. RESULTS: There were three hospital deaths (6%). Thirty-four (72%) patients were free of any atrial tachyarrhythmia events, and 37 (79%) patients were in sinus rhythm by the end of the study's follow-up. During the follow-up, 6 patients (12.7%) experienced atrial flutter and 1 patient had atrial tachycardia. Electrophysiologic study was performed in 5 of 6 patients with postoperative atrial flutter. In 4 of them, the study findings were consistent with left atrial flutter. One patient with typical isthmus-dependent right atrial flutter underwent successful ablation. CONCLUSIONS: Left atrial surgical radiofrequency ablation is associated with a high rate of postoperative atrial flutters that appear to be predominantly of left-sided origin.

Adult↗
PubMed2005

Temporal relationship of implantable cardioverter defibrillator discharges and environmental physical activity.

BACKGROUND: Studies by our group have shown an inverse relationship between sudden death and cardiac rhythm disturbances and environmental levels of geomagnetic activity (GMA). The aim of this study was to use the precise data provided by automatic implantable cardioverter defibrillators (ICDs) regarding the onset of ventricular fibrillation and ventricular tachycardia to link these events to GMA level. PATIENTS AND METHODS: The study group included 25 patients (22 men; 22 with ischemic cardiomyopathy) aged 28-81 years in whom an ICD had been implanted between 1995 and 2004. Patients were referred to the cardiac intensive care unit after each event that induced one or more discharges. The number of events and the day on which they occurred were recorded. Data on GMA and other cosmophysical parameters were obtained from the U.S. National Geophysical and Space Service Centers and the Russian Academy of Sciences. GMA levels, graded from I (quiet) to IV (stormy) in the middle latitutes, were recorded for 1974-2003 (10,954 days) and for each day on which an ICD discharge occurred. RESULTS: A total of 402 discharges were recorded on 137 days during the study period. Forty-six percent of the discharges took place on days of GMA I, compared with 38% - II, 13% - III, and 3% - IV. The daily distribution of GMA was as follows: level I - 35.2%, II - 37.3%, III - 21.86%, IV - 5.61%. Comparison of ICD discharge days and actual multiyear levels of GMA (in percent) yielded a ratio of 1.326 for GMA I, 1.076 - II, 0.459 - III, 0.390 - IV. There was a significant inverse correlation between GMA level and number of discharges (r =-0.97, P = 0.03) and days of treatment (r =-0.96, P = 0.039), and a significant difference between ICD discharges on days of GMA I and GMA II-IV (chi(2)= 5.05, P = 0.02). CONCLUSION: The higher number of ICD discharges on days of lowest GMA may be explained by a possible antiarrhythmic effect of GMA. Environmental arrhythmogenic factors that act inversely to GMA may be activated at times of low GMA.

Adult↗
PubMed2004

Drosophila Su(Hw) insulator can stimulate transcription of a weakened yellow promoter over a distance.

The insulator element from the gypsy transposon is a DNA sequence that blocks activation of a promoter by a transcriptional enhancer when placed between them. The insulator contains reiterated binding sites for the Suppressor of Hairy-wing [Su(Hw)] zinc-finger protein. A protein encoded by another gene, modifier of mdg4 [mod(mdg4)], is also required for the enhancer-blocking activity of the Su(Hw) insulator. Here we present evidence that the Su(Hw) insulator activates a weakened yellow promoter at a distance. Deletion of the upstream promoter region (UPR), located close by the TATA box, significantly reduces yellow expression. The Su(Hw) insulator placed at different positions relative to the yellow promoter partially compensates for loss of the UPR. Su(Hw) is able to stimulate yellow expression even if it is located at a 5-kb distance from the promoter. The stimulatory activity depends on the number of Su(Hw)-binding sites. Mutational analysis demonstrates that only the DNA-binding domain and adjacent regions of the Su(Hw) protein are required for stimulation of yellow transcription.

Animals↗
PubMed2004

Paroxysmal atrioventricular block: clinical experience with 20 patients.

BACKGROUND: Paroxysmal atrioventricular (AV) block is an ill-defined entity, previously described in sporadic cases in association with vasovagal reaction, coronary angiography and distal conduction disease. METHODS: We describe 20 patients (10 women) aged 26 to 80 years with symptomatic paroxysmal AV block. RESULTS: Eight patients had ischemic heart disease-three with dilated cardiomyopathy, and two with co-existing carotid sinus hypersensitivity. Eight were taking chronic AV blockers. In five patients, the paroxysmal AV block occurred during a vagal reaction, in one during migranotic headaches, in one following aortic valve replacement and in one while recovering from acute myocardial infarction. The events lasted between 2.2 and 36 s. In 10 patients, the QRS configuration on the electrocardiogram was wide. Immediate treatment consisted of intravenous atropine and fluid supplements in two patients, discontinuation of the AV blocking agents in four, and the insertion of a temporary pacemaker in eight. Seventeen patients required a permanent pacemaker. CONCLUSIONS: Paroxysmal AV block is an underestimated clinical entity related to vagal reaction, AV blocking drugs and distal conduction disease. Most of our patients eventually required implantation of a permanent pacemaker.

Adult↗
PubMed2004

Atrial signal amplitude measurements in VDD systems according to body position.

Single lead VDD pacing is an established therapy in patients with AV block. Body position may influence the amplitude of the atrial signal recorded through the floating atrial electrode. This study analyzed the degree of posture related variation in the signal amplitude of floating atrial electrodes in 63 patients (mean age 72 +/- 21 years) implanted with a VDD system. The average atrial amplitude in the supine position was 1.59 +/- 1.15 mV and decreased significantly in the sitting position (1.37 +/- 1.08, P < 0.014), right decubitus (1.33 +/- 0.83, P < 0.007), and the abdominal position (1.24 +/- 0.86, P < 0.001). The left side decubitus showed a nonsignificant increase in atrial amplitude (1.66 +/- 1.02, P < 0.64). Body position significantly affects P wave amplitude and may be the cause of intermittent atrial undersensing. P wave amplitude measurement in different body postures should be performed in cases where suspected atrial undersensing occurs.

Aged↗
PubMed2004

Is there a need to remove an old pacemaker when implanting a new device in the contralateral side?

BACKGROUND: Device replacement or revision may constitute 25% of pacemaker procedures. In patients needing pacemaker system replacement the usual approach is from the ipsilateral side of the previous system. In cases where the contralateral side is used the previous pulse generator is removed. OBJECTIVE: To test the feasibility of implanting a new system in the contralateral side without the removal of the old system. METHODS: We present 10 patients, age range 30-88 years (median 73), with clinical indication of pacemaker replacement where the contralateral side was used. In eight patients the replacement was lead-related, and in the remaining two was due to other clinical indications. In all cases the ipsilateral approach was felt to be contraindicated because of local vein and/or pocket complications. Following the new pacemaker implantation the old system was reprogrammed at the lowest rate, lowest output and highest sensitivity. RESULTS: All patients underwent uneventful implantation. Post-surgery monitoring and Holter recordings failed to show any interference by the old system. CONCLUSIONS: In clinically indicated cases it is feasible to implant a new device in the contralateral side without removing the old pulse generator, thereby avoiding an additional surgical procedure and reducing periprocedural complications.

Adult↗
PubMed2003

Bundle branch reentrant ventricular tachycardia in a patient with the Brugada electrocardiographic pattern.

A 55-year-old, previously healthy man presented with an episode of wide QRS tachycardia that had left bundle branch morphology and left superior axis. His electrocardiogram in sinus rhythm showed characteristic Brugada pattern with coved type ST-segment (J-point) elevation in leads V1-V2, mild QRS widening of 110 ms, and left axis deviation. The mechanism of the tachycardia was shown to be bundle branch reentry. Baseline H-V interval of 68 ms additionally lengthened to 119 ms after intravenous procainamide administration indicating significant conduction system disease. The tachycardia was no longer inducible after successful ablation of the right bundle branch.

Bundle-Branch Block↗