Molecular Dynamics Study on the Structure-Property Relationship of Self-Assembled Gear-Shaped Amphiphile Molecules with/without Methyl Groups.

Gaining insight into the encapsulation mechanism is important for controlling the encapsulation rate toward the self-assembly of gear-shaped amphiphile molecules (GSAs). To this aim, we conducted molecular dynamics (MD) simulations for three different hexameric nanocubes (, , and ) of GSAs (, , and , respectively) to elucidate the quantitative structure-property relationship between the stability of the nanocubes and the rate of encapsulation of a guest molecule. The , , and monomers differ from each other in the number of methyl groups, having three, zero, and two methyl groups, respectively.

Missense mutations in the gene encoding prothrombin corresponding to Arg596 cause antithrombin resistance and thrombomodulin resistance.

Antithrombin (AT) and thrombomodulin (TM) play important roles in the process of natural anticoagulation in vivo. Recently, we reported that the prothrombin Yukuhashi mutation (p.Arg596Leu) was associated with AT and TM resistance-related thrombophilia.

Progestin isoforms provide different levels of protein S expression in HepG2 cells.

Introduction: Use of combined oral contraceptives (COCs) results in acquired protein S (PS) deficiency, a well-established risk factor for venous thromboembolism (VTE). The risk of VTE due to COCs containing newer-generation progestins is double compared with COCs containing older-generation progestins, although there is little difference in estrogen contents between the generations. In contrast, progestin-only contraceptives do not confer an increased risk of VTE.

[Antithrombin resistance: a new mechanism of inherited thrombophilia].

Venous thromboembolism is a multifactorial disease resulting from complex interactions among genetic and environmental factors. To date, numerous genetic defects have been found in families with hereditary thrombophilia, but there may still be many undiscovered causative gene mutations. We investigated a possible causative gene defect in a large Japanese family with inherited thrombophilia, and found a novel missense mutation in the prothrombin gene (p.

SVA retrotransposition in exon 6 of the coagulation factor IX gene causing severe hemophilia B.

Hemophilia B is an X-linked recessive bleeding disorder caused by abnormalities of the coagulation factor IX gene (F9). Insertion mutations in F9 ranging from a few to more than 100 base pairs account for only a few percent of all hemophilia B cases. We investigated F9 to elucidate genetic abnormalities causing severe hemophilia B in a Japanese subject.

Antithrombin-resistant prothrombin Yukuhashi mutation also causes thrombomodulin resistance in fibrinogen clotting but not in protein C activation.

Introduction: Prothrombin Yukuhashi (p.Arg596Leu) mutation can result in thrombophilia associated with antithrombin (AT) resistance. Mutant thrombin, an active form of prothrombin Yukuhashi, demonstrated moderately lower clotting activity than the wild-type but substantially impaired the formation of the complex with AT.

A complex genomic abnormality found in a patient with antithrombin deficiency and autoimmune disease-like symptoms.

Hereditary antithrombin (AT) deficiency is an autosomal dominant thrombophilic disorder caused by SERPINC1 abnormality. In the present study, we analyzed SERPINC1 in a Japanese patient with AT deficiency and autoimmune disease-like symptoms. Direct sequencing and multiplex ligation-dependent probe amplification revealed that the patient was hemizygous for the entire SERPINC1 deletion.

Development of a new laboratory test to evaluate antithrombin resistance in plasma.

Introduction: We recently reported a variant prothrombin (p.Arg596Leu: prothrombin Yukuhashi) that confers antithrombin resistance to patients with hereditary thrombosis. To detect antithrombin resistance in plasma, we devised a laboratory test analyzing the kinetics of thrombin inactivation using antithrombin.

Molecular mechanisms of syndecan-4 upregulation by TNF-α in the endothelium-like EAhy926 cells.

Syndecan-4, a cell-surface heparan sulfate proteoglycan, can participate in inflammation and wound healing as a host defense molecule. Tumour necrosis factor (TNF)-α, one of the most potent proinflammatory cytokines, is known to upregulate syndecan-4 expression, but the precise mechanisms are unclear. To elucidate these mechanisms in detail, we examined syndecan-4 upregulation by TNF-α in the endothelium-like EAhy926 cell.

Ribavirin-induced intracellular GTP depletion activates transcription elongation in coagulation factor VII gene expression.

Coagulation FVII (Factor VII) is a vitamin K-dependent glycoprotein synthesized in hepatocytes. It was reported previously that FVII gene (F7) expression was up-regulated by ribavirin treatment in hepatitis C virus-infected haemophilia patients; however, its precise mechanism is still unknown. In the present study, we investigated the molecular mechanism of ribavirin-induced up-regulation of F7 expression in HepG2 (human hepatoma cell line).

Thrombosis from a prothrombin mutation conveying antithrombin resistance.

We identified a novel mechanism of hereditary thrombosis associated with antithrombin resistance, with a substitution of arginine for leucine at position 596 (p.Arg596Leu) in the gene encoding prothrombin (called prothrombin Yukuhashi). The mutant prothrombin had moderately lower activity than wild-type prothrombin in clotting assays, but the formation of thrombin-antithrombin complex was substantially impaired.