Multiple arrhythmogenic substrate for tachycardia in a patient with frequent palpitations

We report a 26-year-old woman with frequent episodes of palpitation and dizziness. Resting electrocardiography showed no evidence of ventricular preexcitation. During electrophysiologic study, a concealed right posteroseptal accessory pathway was detected and orthodromic atrioventricular reentrant tachycardia incorporating this pathway as a retrograde limb was reproducibly induced. After successful ablation of right posteroseptal accessory pathway, another tachycardia was induced using a concealed right posterolateral accessory pathway in tachycardia circuit. After loss of retrograde conduction of second accessory pathway with radiofrequency ablation, dual atrioventricular nodal physiology was detected and typical atrioventricular nodal reentrant tachycardia was repeatedly induced. Slow pathway ablation was done successfully. Finally sustained self-terminating atrial tachycardia was induced under isoproterenol infusion but no attempt was made for ablation. During 8-month follow-up, no recurrence of symptoms attributable to tachycardia was observed.     

Coexistence of atrioventricular nodal reentrant tachycardia and idiopathic left ventricular outflow-tract tachycardia

Double tachycardia is a relatively rare condition. We describe a 21 year old woman with history of frequent palpitations. In one of these episodes, she had wide complex tachycardia with right bundle branch and inferior axis morphology. A typical atrioventricular nodal tachycardia was induced during electrophysiologic study, aimed at induction of clinically documented tachycardia. Initially no ventricular tachycardia was inducible. After successful ablation of slow pathway, a wide complex tachycardia was induced by programmed stimulation from right ventricular outflow tract. Mapping localized the focus of tachycardia in left ventricular outflow tract and successfully ablated via retrograde aortic approach. During 7 month's follow-up, she has been symptom free with no recurrence. This work describes successful ablation of rare combination of typical atrioventricular nodal tachycardia and left ventricular outflow tract tachycardia in the same patient during one session.     

Mass spectrometry of cardiac calsequestrin characterizes microheterogeneity unique to heart and indicative of complex intracellular transit

Cardiac calsequestrin concentrates in junctional sarcoplasmic reticulum in heart and skeletal muscle cells by an undefined mechanism. During transit through the secretory pathway, it undergoes an as yet uncharacterized glycosylation and acquires phosphate on CK2-sensitive sites. In this study, we have shown that active calsequestrin phosphorylation occurred in nonmuscle cells as well as muscle cells, reflecting a widespread cellular process. To characterize this post-translational modification and resolve individual molecular mass species, we subjected purified calsequestrin to mass spectrometry using electrospray ionization. Mass spectra showed that calsequestrin glycan structure in nonmuscle cells was that expected for an endoplasmic reticulum-localized glycoprotein and showed that each glycoform existed as four mass peaks representing molecules that also had 0-3 phosphorylation sites occupied. In heart, mass peaks indicated carbohydrate modifications characteristic of transit through Golgi compartments. Phosphorylation did not occur on every glycoform present, suggesting a far more complex movement of calsequestrin molecules in heart cells. Significant amounts of calsequestrin contained glycan with only a single mannose residue, indicative of a novel post-endoplasmic reticulum mannosidase activity. In conclusion, glyco- and phosphoforms of calsequestrin chart a complex cellular transport in heart, with calsequestrin following trafficking pathways not present or not accessible to the same molecules in nonmuscle.     

Heterogeneous inhibition of horseradish peroxidase activity by cadmium

Inhibition of horseradish peroxidase (HRP) activity by cadmium was studied under steady-state kinetic conditions after preincubation of the enzyme with millimolar concentrations of Cd(2+) for various periods of time. The H(2)O(2)-mediated oxidation of o-dianisidine by HRP was used to assess the enzymatic activity. Cd(2+) was found to be either a noncompetitive inhibitor of HRP or a mixed inhibitor of HRP depending both on the duration of incubation with HRP and on Cd(2+) concentration. Furthermore, for the same inhibition type, K(i) values dropped as incubation time increased. These results suggested that Cd(2+) would slowly bind to the enzyme and progressively induce conformational changes. Spectrophotometric analysis showed that indeed Cd(2+) altered the heme Soret absorption band on binding HRP and exhibited a K(d) which decreased as the incubation time of HRP with Cd(2+) increased. Hill plots suggested a cooperative binding of up to three Cd(2+) ions per molecule of HRP. Thus, Cd(2+) binding to HRP resulted in progressive inhibition of enzymatic activity with a change in the inhibition type as the number of Cd(2+) ions per HRP molecule increased. Results also illustrated the potential danger of long-term exposure to heavy metals, even for enzymes with low affinity for them.     

SeqVis: visualization of compositional heterogeneity in large alignments of nucleotides

Most phylogenetic methods assume that the sequences evolved under homogeneous, stationary and reversible conditions. Compositional heterogeneity in data intended for studies of phylogeny suggests that the data did not evolve under these conditions. SeqVis, a Java application for analysis of nucleotide content, reads sequence alignments in several formats and plots the nucleotide content in a tetrahedron. Once plotted, outliers can be identified, thus allowing for decisions on the applicability of the data for phylogenetic analysis. AVAILABILITY: http://www.bio.usyd.edu.au/jermiin/programs.htm.     

Induction of tumor-specific T-cell responses by vaccination with tumor lysate-loaded dendritic cells in colorectal cancer patients with carcinoembryonic-antigen positive tumors

Background Dendritic cells (DCs) are the most effective antigen-presenting cells. In the last decade, the use of DCs for immunotherapy of cancer patients has been vastly increased. High endocytic capacity together with a unique capability of initiating primary T-cell responses have made DCs the most potent candidates for this purpose. Although DC vaccination occasionally leads to tumor regression, clinical efficacy, and immunogenicity of DCs in clinical trials has not been yet clarified. The present study evaluated the safety and effectiveness of tumor-lysate loaded DC vaccines in advanced colorectal cancer (CRC) patients with carcinoembryonic antigen (CEA) positive tumors. Results Six patients HLA-A*0201-positive were vaccinated with autologous DCs loaded with tumor lysates (TL) together with tetanus toxoid antigen, hepatitis B, and influenza matrix peptides. Two additional patients were injected with DCs that were generated from their sibling or parent with one haplotype mismatch. All patients received the vaccines every 2 weeks, with a total of three intra-nodal injections per patient. The results indicated that DC vaccination was safe and well tolerated by the patients. Specific immune responses were detected and in some patients, transient stabilization or even reduction of CEA levels were observed. The injection of haplotype mismatched HLA-A*0201-positive DCs resulted in some enhancement of the anti-tumor response in vitro and led to stabilization/reduction of CEA levels in the serum, compared to the use of autologous DCs. Conclusion Altogether, these results suggest that TL-pulsed DCs may be an effective vaccine method in CRC patients. Elimination of regulatory mechanisms as well as adjustment of the vaccination protocol may improve the efficacy of DC vaccination. An erratum to this article can be found at