Considerations for simultaneous detection of autoantibodies to coagulation factor and lupus anticoagulant

In patients with autoimmune coagulation factor deficiency (AiCFD), the production of autoantibodies that inhibit coagulation factors in the blood reduces the activity of those relevant coagulation factors, resulting in severe bleeding symptoms. Recently, reports of patients with AiCFD have noted the concomitant detection of lupus anticoagulant (LA), a risk factor for thrombosis. LA-positive patients may show bleeding symptoms due to decreased activity of coagulation factor II (FII) caused by autoantibodies against FII, in addition to thrombotic symptoms, a condition termed LA-hypoprothrombinemia syndrome (LAHPS). Anti-FII antibodies in LAHPS cases are frequently cleared antibodies that can be detected using immunological techniques, such as enzyme-linked immunosorbent assay (ELISA). Recently, several cases of coagulation FV inhibitors, known as autoimmune FV deficiency, have been reported. Some of these cases may be complicated by LA, which can cause thrombosis. False-positive results for anticoagulant inhibitors are known to occur in LA cases; therefore, immunological confirmation of antibodies against coagulation factors is recommended. Additionally, acquired hemophilia A (AHA), caused by autoantibodies against FVIII, is a typical acquired hemorrhagic diathesis, although affected patients may present with thrombosis associated with LA. Thus, it is important to remember that hemorrhagic diathesis due to autoantibodies against clotting factors can also result in thrombosis, as demonstrated by the co-detection of LA. When clotting factor inhibitors are detected in LA-positive individuals, it is important to confirm the presence of autoantibodies against coagulation factors using immunological methods, such as ELISA, to avoid false-positive results

IQGAP1 Is Involved in Post-Ischemic Neovascularization by Regulating Angiogenesis and Macrophage Infiltration

Neovascularization is an important repair mechanism in response to ischemic injury and is dependent on inflammation, angiogenesis and reactive oxygen species (ROS). IQGAP1, an actin-binding scaffold protein, is a key regulator for actin cytoskeleton and motility. We previously demonstrated that IQGAP1 mediates vascular endothelial growth factor (VEGF)-induced ROS production and migration of cultured endothelial cells (ECs); however, its role in post-ischemic neovascularization is unknown.Ischemia was induced by left femoral artery ligation, which resulted in increased IQGAP1 expression in Mac3(+) macrophages and CD31(+) capillary-like ECs in ischemic legs. Mice lacking IQGAP1 exhibited a significant reduction in the post-ischemic neovascularization as evaluated by laser Doppler blood flow, capillary density and α-actin positive arterioles. Furthermore, IQGAP1(-/-) mice showed a decrease in macrophage infiltration and ROS production in ischemic muscles, leading to impaired muscle regeneration and increased necrosis and fibrosis. The numbers of bone marrow (BM)-derived cells in the peripheral blood were not affected in these knockout mice. BM transplantation revealed that IQGAP1 expressed in both BM-derived cells and tissue resident cells, such as ECs, is required for post-ischemic neovascularization. Moreover, thioglycollate-induced peritoneal macrophage recruitment and ROS production were inhibited in IQGAP1(-/-) mice. In vitro, IQGAP1(-/-) BM-derived macrophages showed inhibition of migration and adhesion capacity, which may explain the defective macrophage recruitment into the ischemic tissue in IQGAP1(-/-) mice.IQGAP1 plays a key role in post-ischemic neovascularization by regulating, not only, ECs-mediated angiogenesis but also macrophage infiltration as well as ROS production. Thus, IQGAP1 is a potential therapeutic target for inflammation- and angiogenesis-dependent ischemic cardiovascular diseases

Generation and Characterization of Conditional Heparin-Binding EGF-Like Growth Factor Knockout Mice

Recently, neurotrophic factors and cytokines have been shown to be associated in psychiatric disorders, such as schizophrenia, bipolar disorder, and depression. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family, serves as a neurotrophic molecular and plays a significant role in the brain. We generated mice in which HB-EGF activity is disrupted specifically in the ventral forebrain. These knockout mice showed (a) behavioral abnormalities similar to those described in psychiatric disorders, which were ameliorated by typical or atypical antipsychotics, (b) altered dopamine and serotonin levels in the brain, (c) decreases in spine density in neurons of the prefrontal cortex, (d) reductions in the protein levels of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor and post-synaptic protein-95 (PSD-95), (e) decreases in the EGF receptor, and in the calcium/calmodulin-dependent protein kinase II (CaMK II) signal cascade. These results suggest the alterations affecting HB-EGF signaling could comprise a contributing factor in psychiatric disorder

Synthesis of Polystyrene@TiO₂ Core–Shell Particles and Their Photocatalytic Activity for the Decomposition of Methylene Blue

In this study, we investigated the preparation conditions of polystyrene (PS)@TiO2 core–shell particles and their photocatalytic activity during the decomposition of methylene blue (MB). TiO2 shells were formed on the surfaces of PS particles using the sol–gel method. Homogeneous PS@TiO2 core–shell particles were obtained using an aqueous NH3 solution as the promoter of the sol–gel reaction and stirred at room temperature. This investigation revealed that the temperature and amount of the sol–gel reaction promoter influenced the morphology of the PS@TiO2 core–shell particles. The TiO2 shell thickness of the PS@TiO2 core–shell particles was approximately 5 nm, as observed using transmission electron microscopy. Additionally, Ti elements were detected on the surfaces of the PS@TiO2 core–shell particles using energy-dispersive X-ray spectroscopy analysis. The PS@TiO2 core–shell particles were used in MB decomposition to evaluate their photocatalytic activities. For comparison, we utilized commercial P25 and TiO2 particles prepared using the sol–gel method. The results showed that the PS@TiO2 core–shell particles exhibited higher activity than that of the compared samples

Inclusion Complex of α‑Cyclodextrin with Poly(ethylene glycol) Brush

The inclusion complex (IC) of α-cyclodextrin (α-CD) with poly­(ethylene glycol) (PEG) brush was investigated by neutron reflectometry and grazing-incidence wide-angle X-ray scattering. When the PEG brush was exposed to 10% aqueous α-CD solution, an IC consisting of randomly oriented α-CD polycrystals appeared. On the other hand, when the PEG brush was exposed to 5% aqueous α-CD solution, a uniform 10-nm-thick IC layer with α-CD stacked perpendicular to the substrate was formed. A 10-nm-thick IC was also found in the diluted PEG brush, even when exposed to the 10% α-CD solution. The characteristic 10-nm-thick layer is related to the folded crystalline structure of α-CD on the PEG brush

Repeated rough coiling technique of portosystemic shunt: A novel treatment for hepatic encephalopathy

Hepatic encephalopathy (HE) usually occurs in the end stages of cirrhosis. During these stages, portosystemic shunt (PSS) is one cause of severe HE. Previous reports have demonstrated that shunt embolization is effective in cases involving a large PSS. However, embolization is risky in some patients because severe ascites and esophageal varices may result from aggravation of portal hypertension. Herein, we report a case in which intentional flow reduction was repeatedly performed for spleno-renal shunt using 2 flow reduction methods, debranching and the rough coiling technique, for a patient with severe HE for whom embolization of the whole PSS pathway was risky. Complete embolization was finally achieved by repeated flow reduction over 5 sessions. The patient tolerated treatment well with no ascites for 4 years after total embolization. If embolization of the whole PSS puts the patient at risk for refractory HE, repeatable flow reduction might provide a good alternative path to single-step embolization