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Pathogenesis of venous thromboembolism (VTE) known to be complex and multifactorial process involves the interaction of acquired factors and genetic predisposing conditions. Deficiency of natural anticoagulant factors such as antithrombin (AT), protein C and protein S increases the risk of a VTE. Recently, we have reported novel mechanism of hereditary thrombosis in a Japanese family, in which AT resistance was associated with a missense mutation (p.Arg596Leu) in the prothrombin gene named prothrombin Yukuhashi. The mutant thrombin showed a low clotting activity, but a severely impaired inactivation by AT, resulting in a susceptibility to thrombosis. We have developed a new laboratory test to evaluate AT resistance in plasma. Prothrombin mutation causing AT resistance has found in Caucasian, not only in Japanese.

Recently, various ultrasound contrast agent have been developed all over the world. This paper reviewed recent development of some contrast agent and clinical application of new imaging using contrast agent (Enhanced color Doppler Imaging, Harmonic Imaging, Flash Echo Imaging and Loss of Correlation Imaging). These new methods are easily feasible with a clinical ultrasound diagnosis machine for evaluating further information, for example, slow or deeply located lesion's blood flow, furthermore tissue perfusion. Contrast enhanced ultrasound imaging such as Harmonic imaging is enable to evaluate tissue function.

Cut-off values and grey-zone of tumor markers in blood were described. Cut-off values are a little different from reference intervals, and can discriminate tumor status from non-tumor status. Cut-off values are commonly determined by ROC (receiver operating characteristic) curve, that can show us the diagnostic efficiency of the test. The patients of control group used in ROC curve must be selected from benign diseases whose conditions are similar to those of tumors. Grey-zone is defined as the range between cut-off value from healthy subjects and that from benign diseases. Cost-efficiency must be considered when cut-off values and grey-zone of tumor markers in blood were set up.

Serum isozymes are widely used for estimating the origin or the degree of injury. The significance and future prospect of enzyme immunoassay (EIA) for the determination of isozymes are summarized in this paper. EIAs were developed for isozymes, e.g., unstable or labile, and indistinguishable by electrophoresis or ion-exchange column chromatography EIA can measure isozyme fragments with no catalytic activity. The catalytic activity of isoenzymes released from tissues disappears immediately but immunologically active isozymes or its fragment may remain in the blood for a longer period. The determination of isozymes by EIA provides an accurate mass, released from the injury. The combination assay of catalytic activity with isozyme mass by EIA may open a new approach for the disease.

Technical advances in molecular biology have permitted the detailed study of specific genes in the pathogenesis of inborn errors of metabolism. Analysis of inborn errors of metabolism due to mutations in isoenzyme genes are summarized in this paper. GM2-gangliosidosis results from a deficiency in the activity of beta-N-acetyl hexosaminidase (HEX), and produces two types of diseases: Tay-Sachs and Sandohoff disease, also known as HEX isoenzyme (HEXA and HEXB, respectively) deficiencies. Gene analysis revealed a 5'-defect and point mutation in patients with Tay-Sachs disease. Lactic dehydrogenase has two subunits and two types of deficiency of these two subunits (M and H). Gene analysis revealed a deletion consisting of 20 bp in exon 6 in patients with M subunit deficiency and one of 2 bases in exon 3 in those with H subunit deficiency.