Prognostic value of divergent pattern detection by 99mTc-sestamibi gated SPECT in patients with anterior acute myocardial infarction.

PURPOSE: In gated myocardial perfusion SPECT, apical remodeling may be identified by the presence of a divergent pattern (DP) of the left ventricle (LV). METHODS AND RESULTS: We examined 150 anterior ST-elevation myocardial infarction (STEMI) patients, all successfully treated with primary percutaneous coronary interventions (PCI). Perfusion gated-SPECT to measure infarct size, LV end-diastolic (ED) and end-systolic (ES) volumes and ejection fraction (EF) was acquired before hospital discharge and repeated at 6-month follow-up. DP was observed in 26 patients, who had larger infarct size (28 ± 19% vs. 15.7 ± 17%, P < 0.02), and lower EF (33 ± 7% vs. 41 ± 10%, P < 0.001) than patients without DP. At follow-up, DP patients had significantly larger EDV (156 ± 54 vs. 107 ± 44 mL, P < 0.0001), ESV (104 ± 47 vs. 59 ± 36 mL, P < 0.0001) and lower EF (35 ± 12% vs. 48 ± 13%, P < 0.0001). 54% of DP patients developed remodeling at follow-up vs. 12% of those without DP (P < 0.001). During follow up, 7 events in the DP group (27%) and 11 events in patients without DP (9%; P < 0.02) occurred. Kaplan-Meier survival curves showed a worse prognosis for DP patients. CONCLUSION: In patients with anterior AMI, early DP detection is related to subsequent LV dysfunction, larger infarct size, and worse severity. It is helpful for predicting LV remodeling at short-term follow-up and has prognostic implications.

Duplication of modules facilitates the evolution of functional specialization.

The evolution of simulated robots with three different architectures is studied in this article. We compare a nonmodular feed-forward network, a hardwired modular, and a duplication-based modular motor control network. We conclude that both modular architectures outperform the non-modular architecture, both in terms of rate of adaptation as well as the level of adaptation achieved. The main difference between the hardwired and duplication-based modular architectures is that in the latter the modules reached a much higher degree of functional specialization of their motor control units with regard to high-level behavioral functions. The hardwired architectures reach the same level of performance, but have a more distributed assignment of functional tasks to the motor control units. We conclude that the mechanism through which functional specialization is achieved is similar to the mechanism proposed for the evolution of duplicated genes. It is found that the duplication of multifunctional modules first leads to a change in the regulation of the module, leading to a differentiation of the functional context in which the module is used. Then the module adapts to the new functional context. After this second step the system is locked into a functionally specialized state. We suggest that functional specialization may be an evolutionary absorption state.

1-Peptidyl-2-haloacetyl hydrazines as active site directed inhibitors of papain and cathepsin B.

Fifteen 1-peptidyl-2-haloacetyl hydrazines, which can be considered halometanes of azapeptides containing Phe in P2 and alpha-aza-Ala or alpha-aza-Gly in P1, were synthesized and tested as models of cysteine-proteases inhibitors. By use of kinetic methods, they proved to irreversibly inactivate papain and cathepsin B via a reversible enzyme-inhibitor intermediate. Second-order rate constants of inactivation in the range 26-23000 M-1s-1 were observed for papain and 2000-39600 M-1s-1 for cathepsin B. KI for the reversible EI adducts ranged from 230 to 0.16 microM for papain and from 11 to 0.37 microM for cathepsin B. Structure of possible reversible EI complex is proposed and used to discuss the effects of structural variation of the inhibitors on the kinetic parameters of inactivation. Title compounds proved to be selective for cysteine-proteases, since no inhibiting activity could be detected toward trypsin, chymotrypsin and porcine pancreatic elastase at 0.1 mM concentration, after 6 h incubation. Relatively low aspecific alkylating properties were also verified in tests using glutathione as the nucleophile.