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Remote magnetic navigation for mapping and ablating right ventricular outflow tract tachycardia.

BACKGROUND: Navigation, mapping, and ablation in the right ventricular outflow tract (RVOT) can be difficult. Catheter navigation using external magnetic fields may allow more accurate mapping and ablation. OBJECTIVES: The purpose of this study was to assess the feasibility of RVOT tachycardia ablation using remote magnetic navigation. METHODS: Mapping and ablation were performed in eight patients with outflow tract ventricular arrhythmias. Tachycardia mapping was undertaken with a 64-polar basket catheter, followed by remote activation and pace-mapping using a magnetically enabled catheter. The area of interest was localized on the basket catheter in seven patients in whom an RVOT arrhythmia was identified. Remote navigation of the magnetic catheter to this area was followed by pace-mapping. Ablation was performed at the site of perfect pace-mapping, with earliest activation if possible. RESULTS: Acute success was achieved in all patients (median four applications). Median procedural time was 144 minutes, with 13.4 minutes of patient fluoroscopy time and 3.8 minutes of physician fluoroscopy time. No complications occurred. One recurrence occurred during follow-up (mean 366 days). CONCLUSION: RVOT tachycardias can be mapped and ablated using remote magnetic navigation, initially guided by a basket catheter. Precise activation and pace-mapping are possible. Remote magnetic navigation permitted low fluoroscopy exposure for the physician. Long-term results are promising.

Body Surface Potential Mapping↗

Body surface potential mapping improves detection of ST segment alteration during percutaneous coronary intervention.

BACKGROUND: The 12-lead electrocardiogram underestimates ST segment alteration in acute coronary syndromes compared with multi-lead body surface mapping. We assessed whether 80-lead mapping would improve detection of ST alteration during percutaneous coronary intervention. METHODS: Simultaneous maps and 12-lead electrocardiograms were recorded pre-procedure, during balloon inflation and post-procedure from patients undergoing elective intervention to native coronary arteries. Recordings were obtained from 39 inflations (19 patients). All arteries were successfully stented. RESULTS: Mean 'lead specific' ST alteration (the difference in ST elevation/depression between pre-procedure and inflation recordings in the lead showing maximal ST alteration) was greater on the map than on electrocardiogram, both for ST elevation (0.16+/-0.02 vs. 0.06+/-0.01 mV; p<0.001) and ST depression (0.11+/-0.017 vs. -0.03+/-0.006 mV; p<0.001). During first inflations (n=19), mean lead specific ST elevation and depression on map were greater than on electrocardiogram (0.20+/-0.034 vs. 0.07+/-0.015 mV; p<0.001 and 0.11+/-0.029 vs. 0.03+/-0.009 mV; p=0.001, respectively). Mapping detected greater summated ST elevation and depression during inflation than electrocardiogram (0.04+/-0.005 vs. 0.021+/-0.003 mV; p<0.001 and 0.026+/-0.004 vs. 0.011+/-0.002 mV; p<0.001, respectively). Qualitative analysis of maps and electrocardiograms showed that 21/39 (53.8%) maps recorded during inflation met criteria for myocardial ischaemia compared with 7/39 (17.9%) electrocardiograms (p<0.001). CONCLUSION: Body surface mapping compared with the 12-lead electrocardiogram improves detection of myocardial ischaemia during intervention.

Angioplasty, Balloon, Coronary↗

A first generation physical map of the medaka genome in BACs essential for positional cloning and clone-by-clone based genomic sequencing.

In order to realize the full potential of the medaka as a model system for developmental biology and genetics, characterized genomic resources need to be established, culminating in the sequence of the medaka genome. To facilitate the map-based cloning of genes underlying induced mutations and to provide templates for clone-based genomic sequencing, we have created a first-generation physical map of the medaka genome in bacterial artificial chromosome (BAC) clones. In particular, we exploited the synteny to the closely related genome of the pufferfish, Takifugu rubripes, by marker content mapping. As a first step, we clustered 103,144 public medaka EST sequences to obtain a set of 21,121 non-redundant sequence entities. Avoiding oversampling of gene-dense regions, 11,254 of EST clusters were successfully matched against the draft sequence of the fugu genome, and 2363 genes were selected for the BAC map project. We designed 35mer oligonucleotide probes from the selected genes and hybridized them against 64,500 BAC clones of strains Cab and Hd-rR, representing 14-fold coverage of the medaka genome. Our data set is further supplemented with 437 results generated from PCR-amplified inserts of medaka cDNA clones and BAC end-fragment markers. Our current, edited, first generation medaka BAC map consists of 902 map segments that cover about 74% of the medaka genome. The map contains 2721 markers. Of these, 2534 are from expressed sequences, equivalent to a non-redundant set of 2328 loci. The 934 markers (724 different) are anchored to the medaka genetic map. Thus, genetic map assignments provide immediate access to underlying clones and contigs, simplifying molecular access to candidate gene regions and their characterization.

Animals↗

A comprehensive radiation hybrid map of the bovine genome comprising 5593 loci.

A bovine whole genome 7000-rad radiation hybrid (RH) panel, SUNbRH(7000-rad), was constructed to build a high-resolution RH map. The Shirakawa-USDA linkage map served as a scaffold to construct a framework map of 3216 microsatellites on which 2377 ESTs were ordered. The resulting RH map provided essentially complete coverage across the genome, with 1 cR7000 corresponding to 114 kb, and a cattle-human comparative map of 1716 bovine genes and sequences annotated in the human genome, which covered 79 and 72% of the bovine and human genomes, respectively. We then integrated the bovine RH and comparative maps with BAC fingerprint information in to construct a detailed, BAC-based physical map covering a reported 40-cM quantitative trait locus region for intramuscular fat or "marbling" on BTA 4. In summary, the new, high-resolution SUNbRH7000-rad, comparative, Shirakawa-USDA linkage, and BAC fingerprint maps provide a set of genomic tools for fine mapping regions of interest in cattle.

Animals↗

Atlas of paced body surface QRS integral maps for localization of the site of origin of postinfarction ventricular tachycardia.

Current mapping during radiofrequency (RF) catheter ablation of postinfarction ventricular tachycardia (VT) is based primarily on the use of single-site mapping techniques. Although such techniques are highly suitable for distinguishing the ultimate site where RF energy is delivered by enabling detailed localization of the exit site or critical component of the VT reentrant circuit, they are time-consuming and inefficient for initial rapid identification of the arrhythmogenic target area. This study features the design and preliminary clinical application of a new noninvasive method that is aimed at speeding up the initial phase of the VT mapping procedure. This method is based on the use of an atlas of 62-lead body surface QRS integral map patterns that was previously developed using left ventricular pace mapping in patients with remote anterior or inferior myocardial infarction. The atlas contains 18 and 22 different paced QRS integral map patterns obtained in patients with previous anterior or inferior myocardial infarction, respectively. Each specific QRS pattern in the atlas provides a unique infarct-specific spatial electrocardiographic representation of the onset of ectopic ventricular activation in a circumscribed endocardial segment of the left ventricle. Localization of the segment of VT origin is obtained by visually or mathematically comparing the QRS integral map recorded during VT with one of the two sets of paced QRS integral maps contained within the atlas with the purpose of selecting the best matching paced QRS integral map pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Surface Potential Mapping↗

Construction of a microsatellite linkage map with two sequenced rice varieties.

Based on the successful development of new microsatellite markers from the data of two whole-sequenced rice varieties, japonica variety Nipponbare and indica variety 9311, an F2 population of 90 lines, which was derived from a single cross between Nipponbare and 9311, was applied to construct a genetic linkage framework map. The map covered 2 455.7 cM of total genomic length, and consisted of 152 simple sequence repeats (SSRs) loci including 46 pairs of new SSR primers developed by our research institute. The average genetic distance between two markers was 16.16 cM. In addition, markers RM345 and RM494, which have not been mapped on the Temnykh's map et al. (2001) were anchored on the sixth chromosome of this map. We compared this research with maps of Temnykh et al.(2001) and LAN et al. (2003) regarding the aspects of type and size of population, type and quantity of markers, and the marker arrangement order on chromosome, etc. Results indicated that the similarity of marker linear alignment was 93.81% between this map and T-map. Finally, the important significance of using sequenced rice varieties to construct linkage map was also discussed.

Chromosome Mapping↗

Genetic mapping of tandemly repeated telomeric DNA sequences in tomato (Lycopersicon esculentum).

A telomere-associated tandemly repeated DNA sequence of tomato, TGR I, has been used to map telomeres on the tomato RFLP linkage map. Mapping was performed by monitoring the segregation of entire arrays of TGR I from a segregating F2 population using pulsed-field gel electrophoresis (PFGE). With this strategy, four telomeres have been mapped to the ends of the short arm of chromosomes 9 and 12 and the long arms of chromosomes 5 and 11, using a saturated RFLP map of tomato containing approximately 1000 RFLP markers. In all four cases, the TGR I locus maps to the end of the chromosome, and the distance between the most distal single-copy RFLP marker and the telomeric TGR I locus was between 1.6 and 9.6 cM. This indicates that the region close to the telomeres does not show an excessive rate of recombination compared to other regions of the genome and that the RFLP map of tomato is essentially complete and covers the entire genome for all practical purposes. Additionally, the mapping technique presented here should be generally applicable to the mapping of other tandemly repeated DNA sequences.

Chromosome Mapping↗

Restriction mapping of genes by capillary electrophoresis with laser-induced fluorescence detection.

Restriction mapping is one of the essential steps in gene analysis and molecular biology studies. Slab gel electrophoresis is the traditional way to separate DNA fragments for restriction mapping. However, slab gel electrophoresis does not provide sufficient resolution as required in many mapping applications, and the use of radioisotopes in traditional mapping methods creates health hazards. In the present study, capillary electrophoresis coupled with laser-induced fluorescence detection and a modified partial digestion mapping procedure was developed to map DNA fragments. By using capillary electrophoresis, a restriction map of genomic lambda phage clone of human interleukin 5 receptor alpha chain (IL5R alpha) gene was constructed. The IL5R alpha gene was analyzed to have five XbaI enzyme cutting sites at locations 1370, 2290, 2950, 5430, and 9330. The system was further characterized by using pBluescript SK(+) phagemid DNA as a model. Using a sequence-derived map as a reference, the pBluescript SK(+) restriction map constructed by capillary electrophoresis had an accuracy greater than 90%.

DNA↗

New mapping technology for atrial tachycardias.

UNLABELLED: Prerequisite for succesful radiofrequency catheter ablation of tachycardias is the exact mapping during the electrophysiological study. The new mapping system CARTO allows a three-dimensional color-coded electroanatomic map of impulse propagation using electromagnetic technology. The aim of this study was to determine the feasibility and safety of the new electromagnetic mapping technology CARTO for atrial tachycardias. RESULTS: Electrophysiologic study and CARTO mapping was performed in 38 atrial tachycardias. The mapping procedure took 26 +/- 23 min. We created 33 maps within the right atrium and 5 maps within the left atrium with a mean of 74 +/- 38 different catheter positions. The mechanism was determined as reentrant in 9, junctional in 1 and focal in 28 tachycardias. In focal tachycardias the tachycardia cycle length (CL) and the total atrial activation time (AT) were clearly different (352 +/- 98 ms vs 99 +/- 25 ms). Reentrant tachycardias had a comparable CL and AT (236 +/- 44 ms vs 240 +/- 56 ms). In 83% of the focal tachycardias and in 67% of the reentrant tachycardias, ablation was performed successfully. No complications occured. CONCLUSION: The electroanatomic mapping system allows high resolution visualization of electrical activity and may therefore improve precision and simplify the determination of the arrhythmogenic substrate during tachycardias for successful catheter ablation.

Adult↗

High-density molecular map of chromosome region harboring stripe-rust resistance genes YrH52 and Yr15 derived from wild emmer wheat, Triticum dicoccoides.

Two stripe-rust resistance genes, YrH52 and Yr15, derived from the Israeli wild emmer wheat, Triticum dicoccoides, have been located on chromosome 1B. The main objectives of the present study were to increase marker density in the vicinity of YrH52 gene by means of AFLP, RAPD and microsatellite markers, to improve the map of another T dicoccoides-derived stripe-rust resistance gene Yr15 using microsatellite markers, and to preliminarily discriminate these two genes. Additional 26 marker loci comprising 20 AFLPs, three RAPDs, and three microsatellites were found to be linked to YrH52 gene. An updated genetic map consisting of 45 marker loci, in the region of YrH52 gene, was constructed with a total map length of 107.7 cm. The mean interval length was 0.96 cm in the region Xgwm359b-P55M53b carrying YrH52 gene. YrH52 was bracketed by Xgwm413 (Nor1 and UBC212a) and Xgwm273a (Xgwm273d) with map distance of 1.3 and 2.7 cm from either side, respectively. Eight additional microsatellite markers were found to be linked with Yr15, and the linkage map of Yr15 gene was thus obviously improved. In the YrH52-mapping population, no crossover was detected in the interval UBC212a (Xgwm413)-Yr15-Nor1, and YrH52 was located distally outside this interval. It may suggest that YrH52 is different from Yr15 even though both of them are derived from T. dicoccoides and are mapped on chromosome 1BS. The large number of molecular makers revealed in the present study would be helpful for the marker-assisted introgression of the T. dicoccoides-derived YrH52 and Yr15 stripe-rust resistance genes into elite cultivars of wheat, and the high-density map would accelerate the map-based cloning of the two genes.

Basidiomycota↗

Bi-atrial mapping of atrial arrhythmias.

Cardiac mapping of atrial activation was originally performed in animals during open chest preparations, using epicardial electrodes. The development of endocardial egg-shaped multiple electrodes provided detailed assessment of the minimum number of wavelengths required to sustain atrial fibrillation (AF), as well as the role of interatrial connections during AF. Subsequently, several studies on bi-atrial epicardial high-density mapping in animals and humans also reported on the importance of interatrial connections, as well as the specific characteristics of the left atrium as compared with the right atrium during chronic AF. Endocardial bi-atrial mapping studies using electrode catheters were reported using basket-shaped catheters carrying 64 electrodes. Animal studies suggested that septal activation was asynchronous and discordant, while a human study outlined the multiple origins of atrial ectopic beats following DC cardioversion in patients with chronic atrial fibrillation. The advent of non-fluoroscopic mapping systems significantly changed our approach to percutaneous endocardial mapping. Simultaneous bi-atrial studies using electroanatomic mapping were performed in sinus rhythm as well as in atrial flutter. These studies demonstrated the predominance of interatrial conduction over Bachmann's Bundle and the coronary sinus-left atrial connection during respectively, sinus rhythm and atrial flutter. Simultaneous bi-atrial non-contact mapping was initially performed during porcine studies and later in humans, demonstrating asynchronous and discordant septal activation both during sinus rhythm or left lateral atrial pacing. Preliminary studies from simultaneous bi-atrial non-contact mapping in humans in whom AF occurred spontaneously or was induced suggests three main types of atrial activation, consisting of left atrial drivers causing the right atrium to fibrillate following conduction over interatrial connections, the right atrium independently sustaining AF, even after pulmonary vein disconnection, and both atria fibrillating independently without activation over interatrial connections. Bi-atrial mapping has been essential for our understanding of normal and abnormal atrial activation, and ultimately may provide new approaches for ablation of atrial fibrillation.

Animals↗

Moderate-density molecular maps of Eucalyptus urophylla S. T. Blake and E. tereticornis Smith genomes based on RAPD markers.

Moderate-density molecular maps were constructed for the genomes of Eucalyptus urophylla S. T. Blake and E. tereticornis Smith using RAPD markers and an interspecific cross between the two species. One hundred and eighty-three primers were employed to generate 245 and 264 parent-specific markers in E. urophylla and E. tereticornis, respectively, as well as 49 parent-shared markers. The normally segregating markers, including 208 (84.9%) specific to maternal E. urophylla, 175 (66.3%) to paternal E. tereticornis, and 48 shared by both parents, were used for framework map construction for each parental species. For maternal E. urophylla, the linkage map consisted of 23 linkage groups, 160 framework markers, and 60 accessory markers, defining a total map distance of 1504.6cM and an average interval of 11.0 +/- 8.07 cM. For paternal E. tereticornis, the linkage map contained 23 linkage groups, 126 framework markers, and 92 accessory markers, defining a total map distance of 1035.7 cM and an average interval of 10.1 +/- 7.23 cM. Genome length was estimated at 1585.7 and 1507.5 cM for E. urophylla and E. tereticornis, respectively, indicating map coverage of 94.9 and 68.7% of the corresponding genomes. Construction of such maps will be valuable for quantitative trait loci (QTLs) detection, marker-assisted selection (MAS), comparative mapping, and whole genome based fingerprint characterization in Eucalyptus breeding programs.

Chromosome Mapping↗

Genome-wide mapping with biallelic markers in Arabidopsis thaliana.

Single-nucleotide polymorphisms, as well as small insertions and deletions (here referred to collectively as simple nucleotide polymorphisms, or SNPs), comprise the largest set of sequence variants in most organisms. Positional cloning based on SNPs may accelerate the identification of human disease traits and a range of biologically informative mutations. The recent application of high-density oligonucleotide arrays to allele identification has made it feasible to genotype thousands of biallelic SNPs in a single experiment. It has yet to be established, however, whether SNP detection using oligonucleotide arrays can be used to accelerate the mapping of traits in diploid genomes. The cruciferous weed Arabidopsis thaliana is an attractive model system for the construction and use of biallelic SNP maps. Although important biological processes ranging from fertilization and cell fate determination to disease resistance have been modelled in A. thaliana, identifying mutations in this organism has been impeded by the lack of a high-density genetic map consisting of easily genotyped DNA markers. We report here the construction of a biallelic genetic map in A. thaliana with a resolution of 3.5 cM and its use in mapping Eds16, a gene involved in the defence response to the fungal pathogen Erysiphe orontii. Mapping of this trait involved the high-throughput generation of meiotic maps of F2 individuals using high-density oligonucleotide probe array-based genotyping. We developed a software package called InterMap and used it to automatically delimit Eds16 to a 7-cM interval on chromosome 1. These results are the first demonstration of biallelic mapping in diploid genomes and establish means for generalizing SNP-based maps to virtually any genetic organism.

Arabidopsis↗

Visual cortex maps are optimized for uniform coverage.

Cat visual cortex contains a topographic map of visual space, plus superimposed, spatially periodic maps of ocular dominance, spatial frequency and orientation. It is hypothesized that the layout of these maps is determined by two constraints: continuity or smooth mapping of stimulus properties across the cortical surface, and coverage uniformity or uniform representation of combinations of map features over visual space. Here we use a quantitative measure of coverage uniformity (c') to test the hypothesis that cortical maps are optimized for coverage. When we perturbed the spatial relationships between ocular dominance, spatial frequency and orientation maps obtained in single regions of cortex, we found that cortical maps are at a local minimum for c'. This suggests that coverage optimization is an important organizing principle governing cortical map development.

Animals↗

Integrated human genome-wide maps constructed using the CEPH reference panel.

High resolution linkage maps have proven to be invaluable tools in genetic investigations. We have assembled a collection of genetic maps constructed from primary data collected from investigators performing genotyping using the Centre Etude Polymorphism Humain (CEPH) reference pedigree panel. These maps were constructed using a rigorous, semi-automated map construction algorithm that evaluates the integrity of the maps during construction. Two classes of maps were produced: a high confidence "skeletal" set composed of 544 PCR based markers, and a more highly annotated "framework" set containing maps of 1,123 markers. Genetic map locations within the framework maps are provided for an additional 1,758 loci without statistically unique interval assignments.

Algorithms↗

A radiation hybrid transcript map of the mouse genome.

Expressed-sequence tag (EST) maps are an adjunct to sequence-based analytical methods of gene detection and localization for those species for which such data are available, and provide anchors for high-density homology and orthology mapping in species for which large-scale sequencing has yet to be done. Species for which radiation hybrid-based transcript maps have been established include human, rat, mouse, dog, cat and zebrafish. We have established a comprehensive first-generation-placement radiation hybrid map of the mouse consisting of 5,904 mapped markers (3,993 ESTs and 1,911 sequence-tagged sites (STSs)). The mapped ESTs, which often originate from small-EST clusters, are enriched for genes expressed during early mouse embryogenesis and are probably different from those localized in humans. We have confirmed by in situ hybridization that even singleton ESTs, which are usually not retained for mapping studies, may represent bona fide transcribed sequences. Our studies on mouse chromosomes 12 and 14 orthologous to human chromosome 14 show the power of our radiation hybrid map as a predictive tool for orthology mapping in humans.

Animals↗

Refinement of bovine chromosome 2 linkage map near the mh locus reveals rearrangements between the bovine and human genomes.

The locus responsible for the appearance of muscular hypertrophy (mh) in double muscled cattle breeds has recently been shown to encode a secreted growth factor designated myostatin (MSTN). This conclusion was based in part on the placement of MSTN in the interval to which mh had been mapped on bovine chromosome 2 (BTA2). During the mapping phase of the study, numerous yeast artificial chromosome (YAC) clones were isolated that contained genetic markers closely linked to mh. Other YACs and cosmids were identified that contained genes selected from human chromosome 2q (HSA2q), with the goal of defining the position of breakpoints in conserved synteny between the bovine and human comparative maps, thereby permitting accurate selection of positional candidate genes. An efficient subcloning procedure was developed to obtain microsatellites (ms) from YAC clones, to increase the number of informative meioses in herds segregating for mh. The same procedure was used to place the human orthologues of engrailed-1 (EN1), interleukin 1 beta (IL1B), and paired-box-containing 8 (PAX8) genes on the cattle map to further define the positions of breakpoints in conserved synteny and gene order. Twenty-three of 28 ms identified from YAC subclone libraries were informative in the mapping families. Seven mapped to the centromeric end of BTA2, which contains the mh locus, improving marker density and informativeness. The two MSTN and four EN1 gene-associated ms markers developed from YACs, map to positions 1.5 and 61.6 CM in the BTA2 linkage group, respectively. In addition, ms markers developed from cosmids containing either IL1B or PAX8, map to positions 56.6 and 56.9 CM in the BTA11 linkage group, respectively. These linkage data confirm the location and orientation of orthologous segments of HSA2q that were previously indistinguishable on the bovine map, and demonstrates the presence of microrearrangements of gene order (segments < 10 CM) and conserved synteny between the human and bovine genomes.

Animals↗

p38 MAP kinase regulates TNF alpha-, IL-1 alpha- and PAF-induced RANTES and GM-CSF production by human bronchial epithelial cells.

BACKGROUND: RANTES and granulocyte macrophage-colony stimulating factor (GM-CSF) play an important role in the production of allergic inflammation of the airway through their chemotactic activity for eosinophils. Recent studies have indicated that p38 mitogen-activated protein (MAP) kinase regulates cytokine expression in various cells; however, the role of p38 MAP kinase in RANTES and GM-CSF production in human bronchial epithelial cells (BECs) has not yet been determined. OBJECTIVE: In the present study, we examined serine phosphorylation of MKK3 and MKK6 which is the upstream regulator of p38 MAP kinase and p38 MAP kinase activation in tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha and platelet-activating factor (PAF)-stimulated BECs and the effect of SB 203580 as the specific inhibitor for p38 MAP kinase activity on RANTES and GM-CSF expression in order to clarify the intracellular signal regulating RANTES and GM-CSF production by human BECs. RESULTS: The results showed that TNF alpha, IL-1 alpha and PAF induced serine phosphorylation of MKK3 and MKK6, and p38 MAP kinase activation in BECs. SB 203580 inhibited p38 MAP kinase activity and RANTES and GM-CSF production by TNF alpha-, IL-1 alpha- or PAF-stimulated human BECs. CONCLUSIONS: These results indicate that p38 MAP kinase plays an important role in TNF alpha-, IL-1 alpha- or PAF-activated signalling pathway which regulates RANTES and GM-CSF production by BECs and that the specific inhibitor for p38 MAP kinase activity might be useful for the treatment of allergic inflammation of the airway.

Animals↗