Therapeutic potential of monteplase in acute myocardial infarction.

Thrombolysis with conventional thrombolytic agents prior to percutaneous coronary intervention (PCI) has had no impact on the treatment of acute myocardial infarction (AMI). However, the development of mutant tissue type plasminogen activators (mt-PA) has prompted us to reassess the combination of thrombolysis and PCI. Monteplase is a newly developed mt-PA that can be administered as a single intravenous bolus injection. The results of the COMA (COmbining Monteplase with Angioplasty) trial, suggest that monteplase administration prior to emergent PCI in AMI improves 6-month outcomes and possibly the long-term prognosis of myocardial infarction. Combining monteplase administration on presentation at a community hospital with prompt transfer to a tertiary center for PCI would be an ideal strategy for the treatment of AMI.

Long-term benefits of monteplase before coronary angioplasty in acute myocardial infarction.

Patients with acute myocardial infarction were randomly assigned to receive direct percutaneous coronary intervention (PCI) or pretreatment with intravenous monteplase followed by PCI. Although the combination of monteplase and PCI did not alter mortality compared with direct PCI, there was a dramatic reduction in the cardiac event rate over a 2-year follow-up compared with direct PCI.

Therapeutic potential of monteplase in acute myocardial infarction as a powerful thrombolytic agent for pretreatment of coronary intervention.

Thrombolysis with conventional thrombolytic agents followed by percutaneous coronary intervention (PCI) had no impact on the treatment of acute myocardial infarction (AMI). However, the development of mutant type plasminogen activator (mt-PA) has prompted us to reassess the combination of thrombolysis and PCI. Monteplase (Eisai, Co. Ltd., Tokyo, Japan) is a newly developed mt-PA that can be administrated as a single intravenous bolus injection. We initiated a clinical trial [Combining Monteplase with Angioplasty (COMA)] to evaluate the effectiveness of monteplase followed by PCI. The AMI patients were randomly assigned to receive PCI following pretreatment with a single bolus intravenous injection of monteplase or direct PCI without monteplase. The initial coronary angiography prior to PCI showed that 36.2% of patients in the monteplase group achieved Thrombolysis in Myocardial Infarction (TIMI) 3 flow in the infarct-related artery, compared with in only 7.9% of patients in the direct PCI group (P < 0.0001). During 24 months following PCI, major cardiac events occurred in 27.7% of patients in the monteplase + PCI group, and in 46.7% of patients in the direct PCI group without monteplase (P < 0.05). Thus, the ideal strategy for the treatment of AMI is the administration of monteplase upon arrival at a community hospital with a prompt transfer to a tertiary center for PCI.

Mapping of functional sites on the primary structure of the contractile tail sheath protein of bacteriophage T4 by mutation analysis.

In order to determine the functional roles of amino acid residues in gp18 (gp: gene product), the contractile tail sheath protein of bacteriophage T4, the mutation sites and amino acid replacements of available and newly created missense mutants with distinct phenotypes were determined. Amber mutants were also utilized for amino acid insertion by host amber suppressor cell strains. It was found that mutants that gave rise to a particular phenotype were mapped in a particular region along the polypeptide chain. Namely, all amino acid replacements in the cold-sensitive mutants (cs, which grows at 37 degrees C, but not at 25 degrees C) and the heat-sensitive mutant (hs, lose viability by incubation at 55 degrees C for 30 min) except for one hs mutant were mapped in a limited region in the C-terminal domain. On the other hand, all the temperature-sensitive mutants (ts, grow at 30 degrees C, but not at 42 degrees C) and carbowax mutants (CBW, can adsorb to the host bacterium in the presence of high concentrations of polyethylene glycol, where wild-type phage cannot) were mapped in the N-terminal protease-resistant domain, except for one ts mutant. The results suggested that the C-terminal region of gp18 is important for contraction and assembly, whereas the N-terminal protease-resistant domain constitutes the protruding part of the tail sheath.