Background And Aim: Primary biliary cholangitis (PBC) patients who are refractory to ursodeoxycholic acid (UDCA) are at risk for progression to cirrhosis and liver failure. Bezafibrate could be an alternative second-line therapeutic option in these patients. This study aimed to evaluate the long-term outcome(s) of combined UDCA and bezafibrate therapy in UDCA-refractory PBC patients and identify prognostic factors.
View Article and Find Full Text PDFThe interaction between tumor necrosis factor receptor superfamily, member 4 (OX40) on T cells and the OX40 ligand (OX40L) on antigen‑presenting cells (APCs) is a pivotal step for T‑cell activation and the promotion of antitumor immunity. However, it is hypothesized that soluble OX40 (sOX40) in blood suppresses T‑cell activation by blocking the OX40/OX40L interaction. In the present study, the association between blood sOX40 levels and the clinical characteristics of advanced colorectal cancer (CRC) patients was investigated.
View Article and Find Full Text PDFBackground: Malignant peritoneal mesothelioma (MPeM) is a rare cancer for which no standard systemic chemotherapy has been established. While cisplatin plus pemetrexed, the standard treatment for malignant pleural mesothelioma (MPlM), is usually used for MPeM, its efficacy remains unclear.
Methods: We retrospectively reviewed the medical charts of MPeM patients who had received cisplatin plus pemetrexed as first-line chemotherapy between January 2001 and July 2016 at the National Cancer Center Hospital.
Clinicians sometimes encounter difficulty in choosing a therapeutic strategy due to the uncertainty regarding the type of liver injury. In particular, cholestasis is difficult to diagnose by conventional markers at an early stage of disease. The aim of this study was to identify promising biomarkers for distinguishing the symptom-based types of liver injury (e.
View Article and Find Full Text PDFObjectives. We determined the serum bile acid (BA) composition in patients with liver diseases and healthy volunteers to investigate the relationship between the etiologies of liver disease and BA metabolism. Material and Methods.
View Article and Find Full Text PDFMalaria is one of the most common and serious infectious diseases in the tropics and subtropics. For high-risk travelers to endemic regions, malaria chemoprophylaxis is recommended. Internationally, atovaquone-proguanil (A/P), mefloquine (MEF), or doxycycline (DOX) are the prescribed malaria chemoprophylactic drugs.
View Article and Find Full Text PDFEmerging evidence has suggested environmental factors as causative agents in the pathogenesis of primary biliary cirrhosis (PBC). We have hypothesized that in PBC the lipoyl domain of the immunodominant E2 component of pyruvate dehydrogenase (PDC-E2) is replaced by a chemical xenobiotic mimic, which is sufficient to break self-tolerance. To address this hypothesis, based upon our quantitative structure-activity relationship data, a total of 107 potential xenobiotic mimics were coupled to the lysine residue of the immunodominant 15 amino acid peptide of the PDC-E2 inner lipoyl domain and spotted on microarray slides.
View Article and Find Full Text PDFObjectives: Primary biliary cirrhosis (PBC) is a chronic, progressive cholestatic disease of unknown etiology characterized by serum antimitochondrial antibodies (AMA) directed against a functionally related family of mitochondrial enzymes. We recently suggested that N. aromaticivorans might be the trigger of autoimmunity in PBC.
View Article and Find Full Text PDFPrevious work has demonstrated that immunization of rabbits with the xenobiotic 6-bromohexanoate coupled to BSA breaks tolerance and induces autoantibodies to mitochondria in rabbits. Such immunized rabbits develop high-titer Abs to pyruvate dehydrogenase complex (PDC)-E2, the major autoantigen of primary biliary cirrhosis. In efforts to map the fine specificity of these autoantibodies, rabbits were immunized biweekly with 6-bromohexanoate-BSA and screened for reactivity using a unique xenobiotic-peptide-agarose microarray platform with an emphasis on identifying potential structures that mimic the molecular image formed by the association of lipoic acid with the immunodominant PDC-E2 peptide.
View Article and Find Full Text PDFBackground & Aims: Although considerable effort has been directed toward the mapping of peptide epitopes by autoantibodies, the role of nonprotein molecules has been less well studied. The immunodominant autoantigen in primary biliary cirrhosis (PBC), E2 components of pyruvate dehydrogenase complexes (PDC-E2), has a lipoate molecule bonded to the domain to which autoantibodies are directed.
Methods: We examined sera from patients with PBC (n = 105), primary sclerosing cholangitis (n = 70), and rheumatoid arthritis (n = 28) as well as healthy volunteers (n = 43) for reactivity against lipoic acid.