Fibulin-1 is a protein existing in extracellular matrices and plasma. Although its role is still undefined, binding to fibrinogen and incorporation into fibrin clots seem to suggest its participation in the thrombus formation and its propagation. In this study, we established a sandwich ELISA utilizing a monoclonal and a polyclonal antibody against fibulin-1 as the capture and the second antibody, respectively, and measured fibulin-1 in plasma of patients with various diseases. They include 32 outpatients with stable angina pectoris (s-AP), 17 inpatients with unstable angina pectoris (u-AP), 14 with acute myocardial infarction (AMI), 11 with the disseminated intravascular coagulation syndrome (DIC), and 7 with a liver disease characterized by marked prolongation of the prothrombin time. As control, 16 normal healthy volunteers were enlisted. The sandwich ELISA was shown to have satisfactory coefficients of variation, the within-run and the between-run being 2.5∼3.1% and 6.1∼7.1%, respectively. As compared with the plasma fibulin-1 level in the control group : 33.2 ± 11.4 μg/ml (mean + SD), the fibulin-1 level in plasma was significantly decreased in u-AP : 19.7 ± 5.6 μg/ml and AMI : 16.4 ± 4.9 μg/ml ( both p<0.01 ), whereas no significant decrease was noted in other diseases. In acute coronary diseases such as u-AP and AMI, plasma fibulin-1 may be transferred to and consumed in or around the atherosclerotic lesions, and may also deteriorate the fibulin-1 producing cells. Thus, it seems worthwhile to see the behaviors of this protein in plasma and tissues in various disease conditions for the better understanding of the role of this protein under physiological and pathological conditions, in particular, associated with a higher risk factor for arteriosclerotic diseases.

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We used PCR and direct sequencing to analyze the factor VII (FVII) gene in three unrelated Japanese families with FVII deficiency. Three different missense mutations in the catalytic domain of the FVII were identified. In family 1, the previously-identified mutation Thr 359 (ACG) → Met (ATG) (T 359 M) was identified as homozygous in the proband, who had severe bleeding diathesis. In family 2, a His 348 (CAT) → Gln (CAG) (H 348 Q) mutation was found to be heterozygous in the proband and his father. Two polymorphisms, Arg 353 Gln and a 10-bp insertion (CCTATATCCT) in the 5' flanking region, which are associated with reduced plasma FVII levels, were found to be heterozygous in both the proband and his mother. In family 3, a novel mutation, Gly 283 (GGC) → Ser (AGC) (G 283 S), was found to be heterozygous in an asymptomatic proband and her daughters.

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By a newly developed method using carinactivase-1 (CA-1), we have measured the level of prothrombin in plasma of patients under Warfarin treatment, and studied the effect of Warfarin on the aging. For this aim, we have divided the patients into two groups, i.e., 26 patients at the age of 70 or older, and 106 patients younger than 70. As control, we have selected the age-matched patients, who had not been treated with Warfarin, 32 and 63, respectively. The prothrombin levels in average in these groups were 50.2, 52.4, 116.5 and 116.7 μg/ml, respectively. No significant age-dependent differences were seen in the levels of plasma prothrombin both in the Warfarin-treated patient groups and in the control groups. The average doses of Warfarin given to the patients were 2.9 mg/ml in the older and 2.2 mg/ml in the younger patients. There was a low relationship between the dose of Warfarin and the age, the R and p being 0.221 and 0.0154, respectively. Thus it appears that the requirement of Warfarin to maintain the same prothrombin level in plasma is higher in the younger patients than the older ones.

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