Negative T waves shortly after ST-elevation acute myocardial infarction are a powerful marker for improved survival rate.

BACKGROUND: Recent studies have reported that negative T waves in the setting of acute coronary events are associated with Thrombolysis In Myocardial Infarction flow grade 3 in the infarct-related artery and with improved parameters of ventricular function rather than with ischemia. METHODS: Patients enrolled in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) angiographic substudy (ie, patients with acute infarction randomly assigned to one of 4 thrombolytic regimens who then underwent coronary angiography) were included in this study if they survived at least 24 hours and had no confounding electrocardiographic factors (n = 1505). RESULTS: More patients had negative T waves develop (NT group, n = 938 [62%]) than not (PT group, n = 567 [38%]). Peak creatine kinase MB, time to thrombolysis, and randomization to accelerated alteplase were no different between the groups. Thirty days after admission, 12 patients in the NT group had died versus 25 patients in the PT group (1.3% vs. 4.4%; P <.001; odds ratio for negative T waves 0.28; 95% confidence interval 0.14-0.56). The difference persisted when only patients who survived at least 3 days were analyzed. After adjusting for relevant covariates (including presence of new Q waves in the follow-up electrocardiogram), negative T waves were an independent predictor for survival (P =. 007; odds ratio for negative T waves 0.38; 95% confidence interval 0. 18-0.78). Patients in the NT group were 35% more likely to have achieved patency of the infarct-related artery, although this difference was not statistically significant. CONCLUSIONS: Negative T waves shortly after acute myocardial infarction treated with thrombolysis were markers for improved 30-day survival rate. This finding merits prospective testing.

Staurosporine activates a 60,000 M(r) protein kinase in bovine chromaffin cells that phosphorylates myelin basic protein in vitro.

Bovine chromaffin cells contain a family of renaturable protein kinases. One of these, a 60,000 M(r) kinase (PK60) that phosphorylated myelin basic protein in vitro, was activated fourfold when cells were treated with the protein kinase inhibitor staurosporine. Because staurosporine inhibits protein kinase C, the role of this kinase in the regulation of PK60 activity was investigated. Fifty nanomolar staurosporine produced half-maximal inhibition of protein kinase C activity in chromaffin cells, whereas approximately 225 nM staurosporine was required to induce half-maximal activation of PK60. Other protein kinase C inhibitors, H-7 and K-252a, did not mimic the effect of staurosporine on PK60 activity. Chromaffin cells have three protein kinase C isoforms: alpha, epsilon, and zeta. Prolonged treatment with phorbol esters depleted the cells of protein kinase C alpha and epsilon, but not zeta. Neither activation nor depletion of protein kinase C affected the basal activity of PK60. Moreover, staurosporine activated PK60 in cells depleted of protein kinase C alpha and epsilon; thus, staurosporine appeared to activate PK60 by a mechanism that does not require these protein kinase C isoforms. Incubation of cell extracts with staurosporine in vitro did not activate PK60. Incubation of these extracts with adenosine 5'-O-(3-thiotriphosphate), however, caused a twofold activation of PK60. Although this suggests that PK60 activity is regulated by phosphorylation, the mechanism by which staurosporine activates PK60 is not known. Staurosporine has been reported to promote neurite outgrowth from chromaffin cells. The role of PK60 in mediating the effects of staurosporine on chromaffin cell function remains to be determined.

Nicotinic agonists, phorbol esters, and growth factors activate two extracellular signal-regulated kinases, ERK1 and ERK2, in bovine chromaffin cells.

Treatment of bovine chromaffin cells with nicotinic agonists, phorbol esters, and growth factors increases protein kinase activity toward microtubule-associated protein-2 and myelin basic protein (MBP) in vitro. To characterize the kinases that are activated by these agents, we separated chromaffin cell proteins by electrophoresis in sodium dodecyl sulfate-polyacrylamide gels into which MBP had been incorporated, allowed the proteins to renature, and then assayed MBP kinase activity by incubating the gels with [gamma-32P]ATP. Chromaffin cells contain a family of kinases that phosphorylate MBP in vitro. Two of these kinases, of M(r) 46,000 and 42,000 (PK46 and PK42), were activated by treatment of the cells with dimethylphenylpiperazinium (DMPP), phorbol 12,13-dibutyrate (PDBu), or insulin-like growth factor I (IGF-I). Activation of PK46 and PK42 by DMPP was dependent on extracellular Ca2+, whereas the effects of PDBu and IGF-I were Ca2+ independent. Down-regulation of protein kinase C by incubation of the cells with PDBu abolished the activation of PK46 and PK42 by DMPP, PDBu, and IGF-I. Staurosporine, a protein kinase C inhibitor, prevented the activation of PK46 and PK42 by DMPP and PDBu but did not block the activation of these kinases by IGF-I. Immunoblotting experiments with antiphosphotyrosine (anti-PTyr) antibodies demonstrated that agents that increased the kinase activities of PK46 and PK42 also increased the apparent PTyr content of M(r) 46,000 and 42,000 proteins. PK46 and PK42 comigrated with proteins that reacted with antibodies against extracellular signal-regulated kinases (ERKs). Thus, PK46 and PK42 appear to be the bovine homologues of ERK1 and ERK2.(ABSTRACT TRUNCATED AT 250 WORDS)