Risk stratification and survival in post myocardial infarction patients: a large prospective and multicenter study in Japan

BACKGROUND: Recent clinical trials suggest that the mortality in high-risk patients with ischemic heart disease can be significantly reduced with the use of implantable cardioverter-defibrillator (ICD). Given the high cost and invasiveness of the procedure, it is important to apply it to the patients after myocardial infarction (MI) highly susceptible to sudden arrhythmic death. OBJECTIVE: The purpose of this study was to assess clinical predictors of mortality in post-MI patients in Japan. METHODS AND RESULTS: In 495 consecutive MI survivors, 350 (71%) received acute-reperfusion therapy, whereas 145 (29%) did not. Nonsustained ventricular tachycardia (NSVT) was present in 136 patients (28%) in 24-h ambulatory ECGs at 7+/-6 in-hospital days. Left ventricular dysfunction (LVEF< or =35%) was present in 20/347 patients (5.7%) at 13+/-8 days. Forty-eight patients (9.7%) died during the follow-up period (48+/-13 months); 23 from cardiac and 25 from noncardiac causes. Kaplan-Meier survival analyses showed that mortality rates were higher among patients who were > or =70 years old (log-rank test, P<0.0001); had heart failure at admission (Killip scale> or =2, P=0.001); did not receive acute-reperfusion (P=0.004); and had left ventricular dysfunction with LVEF< or =35% (P=0.02). The presence of NSVT was a significant predictor of death (P=0.036) only in the patients who did not receive acute-reperfusion. Multivariate Cox regression analysis revealed that an independent predictor of total mortality was an age> or =70 (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P<0.00001). CONCLUSIONS: High-risk patients after acute MI can be identified on the basis of age, ventricular dysfunction, heart failure and acute-reperfusion therapy. The presence of NSVT before discharge has a prognostic value only in the patients without acute-reperfusion.     

RNA binding determinant in some class I tRNA synthetases identified by alignment-guided mutagenesis.

The N-terminal nucleotide binding folds of all 10 class I tRNA synthetases (RSs) contain characteristic conserved sequence motifs that define this class of synthetases. Sequences of C-terminal domains, which in some cases are known to interact with anticodons, are divergent. In the 676-amino acid Escherichia coli methionyl-tRNA synthetase (MetRS), interactions with the methionine tRNA anticodon are sensitive to substitutions at a specific location on the surface of the C-terminal domain of this protein of known three-dimensional structure. Although four class I synthetases of heterogeneous lengths and unknown structures are believed to be historically related to MetRS, pair-wise sequence similarities in the region of this RNA binding determinant are obscure. A multiple alignment of all sequences of three of these synthetases with all MetRS sequences suggested a location for the functional analog of the anticodon-binding site in these enzymes. We chose a member of this set for alignment-guided mutagenesis, combined with a functional analysis of mutant proteins. Substitutions within two amino acids of the site fixed by the multiple sequence alignment severely affected interactions with tRNA but not with ATP or amino acid. Multiple individual replacements at this location do not disrupt enzyme stability, indicating this segment is on the surface, as in the MetRS structure. The results suggest the location of an RNA binding determinant in each of these three synthetases of unknown structure.     

Evidence for Reactivation of Human Herpesvirus 6 in Generalized Lymphadenopathy in a Patient with Drug-Induced Hypersensitivity Syndrome

The present case provides direct evidence of human herpesvirus 6 reactivation in resected lymph node tissue in a patient with drug-induced hypersensitivity syndrome. This case clearly demonstrates that appropriate pathological evaluation of lymphadenopathy for drug-induced hypersensitivity syndrome, which mimics malignant lymphoma in clinical, radiological, and pathological findings, is required.     

Isolation and Properties of RNA Replicases Induced by SP and FI Phages

New RNA replicases were isolated and purified from Escherichia coli Q13 infected with SP or FI phages showing different serological properties. These replicases showed a template specificity different from that of Qbeta replicase.