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Three Japanese patients demonstrated plasma prekallikrein (PK) deficiency (PKD) after an examination of the proband family line named 'PKD Seki'. A molecular genetic analysis of these PK genes showed homozygous amino acid substitutions Gly104Arg and Asn124Ser in exon 5, which encodes part of the apple domain 2 (A2) of the heavy chain. This is the first case involving substitutions in the heavy chain of the PK gene which affected blood coagulation. Because the apple domains of PK bind to the C-terminal domain (D6(H)) of high-molecular weight kininogen (HMWK), the two substitutions in A2 may therefore be the main cause of PKD Seki. We subsequently investigated the effects of amino acid substitutions in A2 to elucidate the binding activity of PK to HMWK using mutant A2 proteins produced in Escherichia coli. We clearly demonstrated that the Gly104Arg-substitution with the Asn124Ser-substitution in A2 reduce the binding activity of A2 to HMWK. PKD Seki is the first significant case to show the amino acid substitutions in the A2 affecting the binding capacity of PK with HMWK. Our findings therefore suggest that the binding of PK to HMWK may play a crucial role in the first step of blood coagulation.

Background: Recent studies have suggested that cardiac troponin T (cTnT) and troponin I may detect ongoing myocardial damage involved in the progression of chronic heart failure (CHF). This study was prospectively designed to examine whether the combination of cTnT, a marker for ongoing myocardial damage, and B-type natriuretic peptide (BNP), a marker for left ventricular overload, would effectively stratify patients with CHF after initiation of treatment.

Background: Heart-type fatty acid-binding protein (H-FABP) is proposed as an early biomarker for acute myocardial infarction (AMI), but its prognostic value is unclear in acute coronary syndrome (ACS). We evaluated the prognostic value of the H-FABP concentration relative to cardiac troponin T (cTnT) in the early hours of ACS. Methods: Serum concentrations of H-FABP and cTnT were measured on admission in 328 consecutive patients hospitalized for ACS within 6 h after the onset of chest pain [AMI, 241 (73.5%) patients; ST-segment elevation myocardial infarction, 154 (47.0%) patients; and emergent coronary angiography within 24 h after admission, 287 (87.5%) patients]. Cardiac events, which were defined as cardiac death or subsequent nonfatal AMI, were monitored for 6 months after admission. Results: During the 6-month follow-up period, there were 25 cardiac events, including 15 cardiac deaths and 10 subsequent nonfatal AMIs. Stepwise multivariate analyses including clinical, electrocardiographic, and biochemical variables revealed that increased H-FABP (above the median of 9.8 g/L), but not increased cTnT (above the median of 0.02 g/L), was independently associated with

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