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An episode of stroke in a chronic autochthonous chagasic patient from the Brazilian Amazon is reported. This is the first documented case of a predominantly thromboembolic form of chronic Chagasic cardiopathy in the region.

The patient is a 24-year-old female with a dual-chamber pacemaker, who had intracranial hypertension, progressive visual loss, and several inconclusive cranial tomographies. She underwent magnetic resonance imaging, even though that diagnostic method is absolutely contraindicated in patients with pacemakers.

The case of a 16-year-old patient with atrioventricular tachycardia caused by a single left anterolateral accessory pathway is reported. When the patient underwent radiofrequency ablation, a lesion on the mitral annulus lateral wall produced changes in the retrograde atrial activation pattern determined by that pathway; changes ranged from a delay in depolarization of the annulus posterior portions to full left atrium counterclockwise activation. Such phenomena were probably caused by a block in the isthmus between the annulus and the lower left pulmonary vein ostium. This case illustrates the importance of the mitral-pulmonary isthmus in the process of left atrium activation, an alert to changes induced by its unintentional block during accessory pathway ablation.

Objective: The biventricular pacing (BVP) approach has good results in the treatment of congestive heart failure (CHF) in patients (pts) with disorders of intraventricular conduction., Methods: We have applied BVP to 28 pts, with left ventricular pacing using minitoracotomy in 3 pts and the transvenous approach via coronary sinus in 25 pts. The mean duration of the QRS complexes was 187 ms, in the presence of the left branch block in 22 pts, and right branch block + divisional hemiblock in 6 pts. All pts had been considerated candidates to cardiac transplantation, and were under optimized drug therapy. Sixteen pts were in Functional Class (NYHA) IV, and 12 in class III. The ejection fraction varied from 22 to 46% (average = 34%). The pacing mode employed was biventricular triple-chamber in 22 pts, and bi-ventricular dual-chamber in 6 pts (one with ICD)., Results: The pts were followed up for a period that ranged from 10 days to 14 months (mean 5 months). All pts presented clinical improvement after implant, changing the NYHA Functional Class at the end of follow-up to Class I (9pts), Class II (10 pts) and Class III (6 pts). The initial mean ejection fraction have-raised to 37%. Two pts died suddenly. One patient died due to a pulmonary fungal infection., Conclusion: Ventricular resynchronization through BVP, improved significantly the Functional Class and, therefore, the quality of life. Assessments of myocardial function acutely performed do not reflect the clinical improvement observed.

Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) variants with the K65R or L74V substitution display resistance to several nucleoside analogs. An in vitro dNTP exclusion assay revealed an increased fidelity for K65R RT compared with wild-type RT, but little change for L74V RT. When the forward mutation rates were measured via a gap-filling assay, the K65R variant displayed an 8-fold decrease in the overall mutation rate (1.0 x 10(-3) versus 8.6 x 10(-3) for wild-type HIV-1 RT), whereas the rate for the L74V variant was closer to that for wild-type RT (5.0 x 10(-3)). The increase in overall fidelity observed for K65R RT is the largest reported for any drug-resistant HIV-1 RT variant. Nucleotide sequence analysis of lacZalpha mutants generated by variant RTs indicated that K65R RT displays uniform reduction in most types of errors, whereas L74V RT does not. Modeling the substitutions into the x-ray structure of the ternary complex revealed that the major influence of Leu(74) in stabilizing the templating base is unaffected by Val substitution, whereas the K65R substitution appears to increase the stringency of dNTP binding. It is speculated that the increased fidelity of K65R RT is due to an altered interaction with the dNTP substrate.

The crystal structure of an enzyme-substrate complex with histidyl-tRNA synthetase from Escherichia coli, ATP, and the amino acid analog histidinol is described and compared with the previously obtained enzyme-product complex with histidyl-adenylate. An active site arginine, Arg-259, unique to all histidyl-tRNA synthetases, plays the role of the catalytic magnesium ion seen in seryl-tRNA synthetase. When Arg-259 is substituted with histidine, the apparent second order rate constant (kcat/Km) for the pyrophosphate exchange reaction and the aminoacylation reaction decreases 1,000-fold and 500-fold, respectively. Crystals soaked with MnCl2 reveal the existence of two metal binding sites between beta- and gamma-phosphates; these sites appear to stabilize the conformation of the pyrophosphate. The use of both conserved metal ions and arginine in phosphoryl transfer provides evidence of significant early functional divergence of class II aminoacyl-tRNA synthetases.

The crystal structure at 2.6 A of the histidyl-tRNA synthetase from Escherichia coli complexed with histidyl-adenylate has been determined. The enzyme is a homodimer with a molecular weight of 94 kDa and belongs to the class II of aminoacyl-tRNA synthetases (aaRS). The asymmetric unit is composed of two homodimers. Each monomer consists of two domains. The N-terminal catalytic core domain contains a six-stranded antiparallel beta-sheet sitting on two alpha-helices, which can be superposed with the catalytic domains of yeast AspRS, and GlyRS and SerRS from Thermus thermophilus with a root-mean-square difference on the C alpha atoms of 1.7-1.9 A. The active sites of all four monomers are occupied by histidyl-adenylate, which apparently forms during crystallization. The 100 residue C-terminal alpha/beta domain resembles half of a beta-barrel, and provides an independent domain oriented to contact the anticodon stem and part of the anticodon loop of tRNA(His). The modular domain organization of histidyl-tRNA synthetase reiterates a repeated theme in aaRS, and its structure should provide insight into the ability of certain aaRS to aminoacylate minihelices and other non-tRNA molecules.