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Biomedical subjects

Carlos Salazar

Publications and source records attributed to Carlos Salazar.

6 recordsLinked to original sources
PubMed2006

Thoracoscopic sympathectomy for incessant polymorphic ventricular tachycardia in chronic chagasic myocarditis--a case report.

Management of complex ventricular arrhythmias due to chagasic myocarditis is challenging. We herein present the case of a young male who was presented with incessant well tolerated polymorphic ventricular tachycardia of unknown cause, who was unresponsive to conventional medical management and as a last resort was submitted to a thoracoscopic bilateral sympathectomy, and showed remarkable improvement in his arrhythmia control. Later on his tests returned positive for Chagas' disease and shortly thereafter he suddenly died.

Adult↗
PubMed2005

Kinetic models of phosphorylation cycles: a systematic approach using the rapid-equilibrium approximation for protein-protein interactions.

Activation-inactivation cycles of signalling proteins and transcription factors catalysed by kinases and phosphatases are a core component of cellular signal transduction. We present a systematic kinetic analysis of a phosphorylation cycle that starts from the description of elementary protein-protein interaction and catalytic steps. A rapid-equilibrium approximation for protein interactions is used to reduce the set of parameters. The resulting description consists of a kinetic equation for the phosphorylation of the target and a set of conservation conditions for kinase and phosphatase. Generally no explicit rate laws exist for the two enzymes; linear or Michaelis-Menten rate equations can be obtained in special cases. Key parameters that determine the stimulus-response curve and the response time of the cycle are the concentrations of kinase and phosphatase relative to the target protein and the affinities of the two enzymes for the different phosphorylation states of the target. Characterizing the response curve by the global response coefficient, we obtain a phase diagram that shows the existence of three kinds of behaviours: graded, ultrasensitive, and a previously undescribed biphasic response. Two kinds of competition effect turn out to shape the behaviour: (1) the degree of product inhibition of each enzyme, and (2) the competition between kinase and phosphatase to bind the target protein, as determined by their relative target affinities. The approach outlined here may be useful also for analysing more complex systems, including multiple phosphorylation and kinase cascades.

Computer Simulation↗
PubMed2005

Activation of the transcription factor NFAT1: concerted or modular regulation?

The transcription factor NFAT1 is activated through dephosphorylation of multiple serine residues, contained within the SRR1 and SP motifs. The phosphorylation status of these motifs regulates the subcellular localisation of NFAT1 via a conformational switch. Here, we discuss two molecular mechanisms for NFAT1 activation that resemble network-oriented approaches. In the modular mechanism, import and export are regulated separately by the SRR1 and SP motifs, respectively, whereas in the concerted model all residues jointly control both processes. Using simulations of a computational model, we show that both mechanisms may be compatible with recent experimental data on the import and export kinetics of NFAT1.

DNA-Binding Proteins↗
PubMed2003

Allosteric regulation of the transcription factor NFAT1 by multiple phosphorylation sites: a mathematical analysis.

NFAT transcription factors are activated through dephosphorylation by the phosphatase calcineurin. Experimental data show that 13 conserved phosphorylation sites conspire to control the transition between an inactive and an active conformation. We propose a quantitative model of the underlying molecular mechanisms that may generally apply to highly phosphorylated proteins. Mathematical analysis shows that multiple phosphorylation sites result in a threshold for protein activation. Its sharpness increases with the number of sites, thus providing a rationale for the involvement of the large number of serine residues in NFAT activation. The model predicts that nuclear kinases exert a larger control on the activation threshold than cytoplasmic kinases, and that the NFAT activation kinetics can discriminate between input signals of different amplitude.

Allosteric Regulation↗
PubMed2003

[Iatrogenic ureteral injury].

OBJECTIVES: To determine the most frequent causes of ureteral injury, and the way to correct severe damage of the ureter. METHODS: We reviewed the medical records of 25 patients who suffered ureteral injuries during abdominal or pelvic surgery in a five-year period; endoscopic injuries were excluded. RESULTS: The most common presentation included pain, urinary incontinence and fever. Hysterectomy was the most frequent operation causing ureteral injuries. The diagnosis was made by intravenous urography and ultrasound. Ureteral reimplantation using a Boari's flap, without other complications, was the preferred treatment due to ureteral damage. Right side and distal third of the ureter where the most frequently affected sites. CONCLUSIONS: In cases of iatrogenic injuries of the distal third of the ureter with severe lesions, ureteral reimplantation with a Boari's flap may be the option.

Adult↗