Cardiovascular proteomics: tools to develop novel biomarkers and potential applications.

Proteomics is the new systems biological approach to the study of proteins and protein variation on a large scale as a result of biological processes and perturbations. The field is undergoing a dramatic transformation, owing to the completion and annotation of the human genome as well as technological advances to study proteins on a large scale. The new science of proteomics can potentially yield novel biomarkers reflecting cardiovascular disease, establish earlier detection strategies, and monitor responses to therapy.

Airway management of a rare huge-size supraglottic mass.

Laser excision of a huge-sized supraglottic mass nearly obstructing the airway passage is a real challenge to anesthesiologists. Upper airway obstruction due to neoplasm in supraglottic region, is traditionally managed by preoperative tracheostomy, however, such a common procedure can potentially have an impact on long-term outcome. A 26-year-old patient presented with dysphagia caused by left cystic vallecular synovial sarcoma.

Stem cell factor receptor induces progenitor and natural killer cell-mediated cardiac survival and repair after myocardial infarction.

Inappropriate cardiac remodeling and repair after myocardial infarction (MI) predisposes to heart failure. Studies have reported on the potential for lineage negative, steel factor positive (c-kit+) bone marrow-derived hematopoetic stem/progenitor cells (HSPCs) to repair damaged myocardium through neovascularization and myogenesis. However, the precise contribution of the c-kit signaling pathway to the cardiac repair process has yet to be determined.

Heart failure in the post-genomics era: gene-environment interactions.

Cardiovascular diseases remain the major cause of mortality and morbidity in the Western world. Heart failure is the most rapidly rising cardiovascular condition and is associated with high mortality. The etiology of heart failure is multiple, ranging from genetic cardiomyopathies to structural modifications to the heart following myocardial infarction or long-standing high blood pressure.

The remote ischemic preconditioning stimulus modifies gene expression in mouse myocardium.

Background: We have recently demonstrated that remote ischemic preconditioning reduces ischemia-reperfusion injury in animal models. The mechanisms by which the remote ischemic preconditioning stimulus exerts its effect remain to be fully defined, and its effect on myocardial gene expression is unknown. We tested the hypothesis that remote ischemic preconditioning modifies myocardial gene expression immediately after the remote ischemic preconditioning stimulus (early phase) and 24 hours later (late phase).

Prediction of protein secondary structure based on residue pair types and conformational states using dynamic programming algorithm.

We have used a statistical approach for protein secondary structure prediction based on information theory and simultaneously taking into consideration pairwise residue types and conformational states. Since the prediction of residue secondary structure by one residue window sliding make ambiguity in state prediction, we used a dynamic programming algorithm to find the path with maximum score. A score system for residue pairs in particular conformations is derived for adjacent neighbors up to ten residue apart in sequence.

Expression of interleukin-5, interleukin-8, and interleukin-10 mRNA in the osteomeatal complex in nasal polyposis.

Background: Several cytokines are expressed in chronic sinusitis with and without underlying allergy. Their local production and regulation in the osteomeatal complex, the key area of paranasal sinuses, still is not fully understood. This study was performed to investigate differences of cytokine messenger RNA (mRNA) expression between the medial and the lateral part of the middle turbinate and anterior ethmoid mucosa of allergic and nonallergic patients.

The role of endothelin-1 in myocarditis and inflammatory cardiomyopathy: old lessons and new insights.

Endothelin-1 has emerged as an important participant in the pathophysiology of a variety of cardiovascular diseases, where it may act on endocrine, paracrine and autocrine bases. Here we review its regulated biosynthesis, receptor-mediated signaling, and functional consequences in the heart, with particular emphasis on cardiac development and disease. Exploring published data employing molecular genetic mouse models of endothelin dysregulation, we highlight its heretofore underappreciated role as a pro-inflammatory cytokine.

The remote ischemic preconditioning stimulus modifies inflammatory gene expression in humans.

Remote ischemic preconditioning (IPC) reduces tissue injury caused by ischemia-reperfusion (IR) in distant organs. We tested the hypothesis that remote IPC (rIPC) modifies inflammatory gene transcription in humans. Using a microarray method, we demonstrated that a simple model of brief forearm ischemia suppresses proinflammatory gene expression in circulating leukocytes.

Consanguinity and endogamy in Northern Tunisia and its impact on non-syndromic deafness.

Deafness is an important health problem in the Tunisian population, especially in isolates where the prevalence ranges from 2 to 8%. To evaluate the effect of inbred unions on deafness, a study was conducted on 5,020 individuals (160 are deaf) between 2000 and 2002 in the North of Tunisia. The coefficient of inbreeding for all individuals and the levels of inbreeding in ten districts were computed.

Inhibition of voltage-gated calcium currents in type II vestibular hair cells by cinnarizine.

Cinnarizine is pharmaceutically used in conditions with vestibular vertigo such as Meniere's disease. It is thought to act on extra-vestibular targets. We hypothesized that cinnarizine, as a blocker of L-type Ca2+ channels, may directly target vestibular hair cells where Ca2+ currents are important for the mechano-electrical transduction and transmitter release.

Day/night rhythms in gene expression of the normal murine heart.

Molecular circadian oscillators have recently been identified in heart and many other peripheral organs; however, little is known about the physiologic significance of circadian gene cycling in the periphery. While general temporal profiles of gene expression in the heart have been described under constant lighting conditions, patterns under normal day/night conditions may be distinctly different. To understand how gene expression contributes to cardiac function, especially in human beings, it is crucial to examine these patterns in 24-h light and dark environments.

Hematopoietic protein tyrosine phosphatase suppresses extracellular stimulus-regulated kinase activation.

The mitogen-activated protein kinases (MAPKs) are signaling molecules that become enzymatically activated through phosphorylation by diverse stimuli. Hematopoietic cytokines, growth factors, and stimulated lymphocyte antigen receptors may activate specific MAPKs by altering the balance of MAPK-activating protein kinases and the protein phosphatases that target their activation sites. Hematopoietic protein tyrosine phosphatase (HePTP) is a hematopoiesis-specific cytoplasmic protein tyrosine phosphatase whose expression is induced by mitogenic stimuli.

Molecular cytogenetic analysis of glial tumors using spectral karyotyping and comparative genomic hybridization.

Background: Glial tumors are the most common tumors of the central nervous system, affecting individuals of all ages. Conventional cytogenetics have been unable to identify a consistent chromosomal translocation or rearrangement in this group of tumors; thus, more advanced molecular cytogenetic approaches are required.

Methods And Results: In this study, 16 glial tumors, including two recurrences and six glioma cell lines, were analyzed by spectral karyotyping (SKY) and comparative genomic hybridization (CGH).

[Otosclerosis in populations living in northern Tunisia: epidemiology and etiology].

Otosclerosis is a hereditary disease frequently encountered in Caucasian populations (0.1 to 2% prevalence). In Tunisia, prevalence varies from 0.

Prediction of protein surface accessibility with information theory.

A new, simple method based on information theory is introduced to predict the solvent accessibility of amino acid residues in various states defined by their different thresholds. Prediction is achieved by the application of information obtained from a single amino acid position or pair-information for a window of seventeen amino acids around the desired residue. Results obtained by pairwise information values are better than results from single amino acids.

Mutations of GJB2 in three geographic isolates from northern Tunisia: evidence for genetic heterogeneity within isolates.

Geographically isolated populations have been successfully used to localize genes for recessive inherited diseases, including non-syndromic sensorineural recessive deafness (NSRD). To date, 25 loci for NSRD have been localized on human chromosomes (DFNB loci), and six of the corresponding genes have been identified. Here, we report on the contribution of the DFNB1 locus (GJB2 gene) to NRSD in seven affected families living in three northern Tunisian geographic isolates, and we provide evidence for genetic heterogeneity within isolates.

Mosaicism for a small marker chromosome resulting from a familial Robertsonian translocation (21;22).

A mosaic marker chromosome found in amniotic fluid was shown to have originated from the proximal part of the long arm of chromosome 22. This marker is unusual because it is the result of a deletion of a maternally inherited Robertsonian 21;22 translocation. It is suggested that the deletion and marker formation probably occurred post zygotically in the fetus.

Verotoxin induces apoptosis and the complete, rapid, long-term elimination of human astrocytoma xenografts in nude mice.

Verotoxin 1 (VT1) is an E. coli elaborated subunit toxin active only against (tumor) cell lines that express the VT1 receptor, globotriaosyl ceramide-Gb3. Astrocytomas can be highly malignant brain tumors that remain refractory to clinical treatment.

Balloon dilation of the right ventricular outflow tract in tetralogy of Fallot: a palliative procedure.

Fifteen patients requiring palliation for tetralogy of Fallot were treated by balloon dilation because of hypercyanotic spells. The mean age at dilation was 1.9 +/- 0.

Intracellular targeting of the endoplasmic reticulum/nuclear envelope by retrograde transport may determine cell hypersensitivity to verotoxin via globotriaosyl ceramide fatty acid isoform traffic.

The pentameric B subunit of verotoxin (VT) mediates the attachment to cell surface globotriaosyl ceramide (Gb3) to facilitate receptor-mediated endocytosis of the toxin. In highly toxin-sensitive tumor cells, the holotoxin and VT1 B subunit is targeted intracellularly to elements of the endoplasmic reticulum (ER)/nuclear membrane. In less sensitive cells, the toxin is targeted to components of the Golgi apparatus.

Verotoxins inhibit the growth of and induce apoptosis in human astrocytoma cells.

Verotoxin 1 (VT1) is an E. coli toxin comprising an A subunit with N-glycanase activity, and five smaller B subunits capable of binding to the functional receptor globotriaosylceramide (Galalpha1-4-Galbeta1-4-Glcceramide-Gb3). VT is implicated in hemorrhagic colitis and the more serious hemolytic uremic syndrome.