Publications by authors named "Yuto Nakajima"

Ion mobility spectrometry (IMS) (also including IMS-IMS measurements) as well as DFT calculations have been used to study isomer distributions and isomer interconversion in a range of electrospray-generated lanthanide chloride cluster anions, LnCl (where = 1-6, and Ln corresponds to the 15 lanthanide elements (except for radioactive Pm)). Where measurement and structural rearrangement timescales allow, we obtain almost quantitative agreement between experiment and theory thus confirming isomer predictions and reproducing isomer intensity ratios. LnCl structures reflect strong ionic bonding with limited directionality.

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Recombinant porcine factor VIII (rpFVIII) is a hemostatic agent for acquired hemophilia A (AHA). Cross-reaction of auto-antibodies against rpFVIII has been reported, although no data are available in Japanese patients. This study investigated the cross-reactivity and coagulation potential of rpFVIII in plasma samples from Japanese patients with AHA.

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In patients with hemophilia A with inhibitor (PwHA-I), emicizumab drastically reduces bleeding events. However, few studies have investigated the behavior and effects of factor X (FX) in patients who require intensive treatment with factor VIII-bypassing agents (BPA) and emicizumab. A 59-year-old man with HA-I receiving emicizumab prophylaxis was admitted to our hospital because of acute gangrenous cholecystitis.

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Background: Venous thromboembolic events have been reported in persons with hemophilia A who received emicizumab and activated prothrombin complex concentrate (APCC) concomitantly, but the relevant mechanism(s) remains unclear. We speculated that activated protein C (APC) and antithrombin (AT) resistance might be associated with these adverse events.

Objectives: To investigate APC and AT resistance in factor (F)VIII-deficient (FVIIIdef) plasma in the presence of emicizumab and APCC.

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Article Synopsis
  • The patient received multiple doses of rFVIIa around the time of surgery, and there were no bleeding or thrombotic complications reported during and after the operation.
  • The study suggests that using rFVIIa every 8 hours may be effective for managing bleeding risks in patients treated with emicizumab during surgery.
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Background: Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare disease caused by acquired factor II (FII) deficiency and lupus anticoagulant. Patients with LAHPS typically present with thrombosis and bleeding. However, little information is available on the evaluation of coagulation potential in patients with LAHPS.

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Article Synopsis
  • A2 domain dissociation in activated factor VIII (FVIIIa) leads to reduced activity, but certain mutations (D519V/E665V and K1813A) can enhance coagulation potential due to delayed dissociation.* -
  • The study assessed a combination mutation (D519V/E665V/K1813A) and found it significantly improved FVIII's performance in coagulation, showing a higher enzyme activity compared to wild-type FVIII.* -
  • In tests with hemophilia A mice, the D519V/E665V/K1813A mutant exhibited an approximately eightfold increase in hemostatic function over wild-type FVIII, indicating a potential for improved treatment options.*
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Background:  Bypassing agents are used for breakthrough bleedings in patients with hemophilia A with inhibitor (PwHAwI) receiving emicizumab prophylaxis. Previous study demonstrated a weak binding affinity between emicizumab and factor (F)X ( ; 1.85 μM), and that this value was much greater than the plasma FX concentration (∼130 nM).

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Background: Activated protein C (APC) inactivates activated factor (F) V (FVa) and FVIIIa. NXT007, an emicizumab-based engineered therapeutic bispecific antibody, enhances the coagulation potential of FVIII-deficient plasma (FVIIIdef-plasma) to near normal levels. However, little is known about the effect of APC-induced inactivation in NXT007-mediated hemostatic function.

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Article Synopsis
  • * The study examined the effects of adding proteins like protein C, protein S, and antithrombin to simulated hemophilia A plasma with emicizumab to assess their role in thrombin generation.
  • * Results showed that emicizumab increases thrombin levels depending on the concentrations of these natural anticoagulants, suggesting a complex interaction that could help regulate clotting in patients with hemophilia A who also have thrombophilic tendencies.
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Introduction: Porcine factor (pF)VIII has low cross-reactivity with anti-human (h)FVIII inhibitor alloantibodies. Clinical trials of pFVIII in congenital haemophilia A patients with inhibitor (PwHA-I) are in progress. Most polyclonal anti-hFVIII inhibitors recognize its A2 and/or C2 domain(s), and recombinant human-porcine hybrid (hp)FVIII proteins may escape neutralization by these inhibitors.

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Background: We previously demonstrated that factor (F)VIII was rapidly activated through proteolytic cleavage at Arg and Arg by activated FVII (FVIIa)/tissue factor (TF) in very early coagulation phase, followed by inactivation by cleavage at Arg. The influence of the absence of FVIII B domain in this series of FVIIa/TF-catalyzed reaction remains unclear, however.

Aim: To examine the FVIIa/TF-catalyzed reaction of B domain-deleted (BDD-)FVIII.

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Emicizumab prophylaxis dramatically reduces bleeding events in patients with hemophilia A (PwHA) with or without factor VIII (FVIII) inhibitors. However, long-term dynamic changes in FVIII inhibitor titers during emicizumab prophylaxis remain to be investigated. We conducted a retrospective follow-up study of FVIII inhibitor titers after initiation of emicizumab prophylaxis in 25 PwHA carrying current or historical FVIII inhibitors.

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Article Synopsis
  • Emicizumab is effective in reducing bleeding for patients with hemophilia A (PwHA), particularly in a study involving infants and toddlers under 12 months old.
  • A study analyzed plasma samples from 14 young PwHA, focusing on how emicizumab affects coagulation compared to other treatments or no treatment at all.
  • Results showed that emicizumab improved coagulation potential in most samples, indicating its potential benefits for young patients with hemophilia A.
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Structures of platinum oxide cluster cations (PtO) were studied by ion mobility-mass spectrometry in combination with theoretical calculations. Structures of oxygen-equivalent PtO ( = 3-7) clusters were discussed from the comparison between their collision cross sections (CCSs) obtained by mobility measurement and simulated CCSs of their structural candidates from structural optimization calculations. Assigned structures of PtO were found to be composed of Pt frameworks and bridging O atoms, which follows the previous theoretical prediction on the neutral clusters.

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Background: Hemophilia A (HA) is a hereditary bleeding disorder caused by defects in endogenous factor (F)VIII. Approximately 30 % of patients with severe HA treated with FVIII develop neutralizing antibodies (inhibitors) against FVIII, which render the therapy ineffective. The managements of HA patients with high-titter inhibitors are especially challenging.

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Factor V (FV) plays pivotal roles in both procoagulant and anticoagulant mechanisms. Genetic mutations, FV-W1920R (FVNara) and FV-A2086D (FVBesançon), in the C1 and C2 domains of FV light chain, respectively, seem to be associated with deep vein thrombosis. However, the detailed mechanism(s) through which these mutations are linked to thrombophilia remains to be fully explored.

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Background: Elevated factor VIII activity (FVIII:C) is often observed in patients with acquired hemophilia A (PwAHA) in remission. However, comprehensive coagulation potentials in this patient group remain to be investigated.

Aim: To evaluate comprehensive coagulation potentials in PwAHA.

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Emicizumab reduces bleeding episodes in patients with severe hemophilia A (PwHA). Little information is available on hemostatic management of severe traumatic hemorrhages in emicizumab-treated pediatric PwHA. We assessed therapeutic efficacy and global coagulation potentials in two pediatric cases of emicizumab-treated pediatric PwHA with intracranial or retroperitoneal/iliopsoas hemorrhage.

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Factor VIII (FVIII) functions as a cofactor of FIXa for FX activation in the intrinsic tenase complex. The 1811-1818 region in the FVIII A3 domain was observed to contribute to FIXa binding, and the K1813A/K1818A mutant increased the binding affinity for FIXa. The current study aims to identify mutated FVIII protein(s) that increase FVIIIa cofactor activity in the 1811-1818 region.

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