Macrophage behaviour 72 hours after implantation of biodegradable polymer-based sirolimus-eluting stent in a case of ST elevation myocardial infarction.

While the vascular healing process after drug-eluting stent implantation is not fully elucidated, it is generally accepted that macrophages play an important role in inflammation. It is also known that macrophages involved in the pathogenesis of atherosclerosis may stem from several origins, that is, monocyte-derived macrophages versus resident macrophages. However, little is known about the role of human macrophages on reperfusion of culprit coronary arteries in patients with atherosclerotic disease who have sustained acute coronary syndrome.

VEGF-C/VEGFR-3 signalling in macrophages ameliorates acute lung injury.

Background: Successful recovery from acute lung injury requires inhibition of neutrophil influx and clearance of apoptotic neutrophils. However, the mechanisms underlying recovery remain unclear. We investigated the ameliorative effects of vascular endothelial growth factor (VEGF)-C/VEGF receptor 3 (VEGFR-3) signalling in macrophages in lipopolysaccharide (LPS)-induced lung injury.

Drebrin: A new oncofetal biomarker associated with prognosis of lung adenocarcinoma.

Objectives: With the aim of searching for novel oncofetal tumor biomarkers of lung adenocarcinoma other than carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP), we developed a strategy involving monoclonal antibodies generated from embryonic tissue of miniature swine.

Materials And Methods: Using immunohistochemistry, we selected suitable hybridoma clones that were reactive against swine fetal lung but not adult lung using tissue microarray loading of human normal lung, lung cancer, and fetal and adult swine tissues.

Results: The selected clones included several that were uniquely reactive against both swine fetal lung and human lung adenocarcinoma, and protein microarray revealed that the antigen they recognized was "drebrin" (DBN1).

Development of Lymphatic Capillary Network Along the Alveolar Walls of Autopsied Human Lungs with Pneumonia.

Background: Limited information is available regarding the lymphatic vasculature during pneumonia.

Objective: To characterize lymphatic vasculatures in autopsied cadavers with pneumonia.

Methods: Paraffin-embedded lung tissues obtained from 20 autopsied cadavers with complicated pneumonia and 10 control cadavers without pneumonia were used for immunohistochemical analyses using primary antibodies against podoplanin, vascular endothelial growth factor receptor-3 (VEGFR-3), CD34, vascular endothelial growth factor (VEGF)-C, VEGF-D, CD73, and CD163.

Nuclear factor erythroid 2-related factor 2 is a critical target for the treatment of glucocorticoid-resistant lupus nephritis.

Background: Dimethyl fumarate (DMF), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator, has been proven effective for the systemic treatment of multiple sclerosis. The aim of this study is to evaluate the anti-inflammatory effects of Nrf2 activators on human renal mesangial cells (HRMCs) and the development of lupus nephritis (LN) in mice.

Methods: To assess Nrf2 activation in vitro, HRMCs were treated with safe doses of Nrf2 activators and prednisolone.

Molecular Diversity of Macrophages in Allergic Reaction: Comparison between the Allergenic Modes; Th1- and -Th2-Derived Immune Conditions.

Activated macrophages have been classified into classical (M1) and alternative (M2) macrophages. We aimed to establish a method to yield enough number of macrophages to analyze their molecular, biological and immunological functions. We used drugs; adjuvant albumin from chicken egg whites--Imject Alum (OVA-Alum) and OVA Complete Freund Adjuvant (OVA-CFA), to induce macrophages to M2 and M1 respectively.

Interleukin-17 is a critical target for the treatment of ankylosing enthesitis and psoriasis-like dermatitis in mice.

Ankylosis is a major pathological manifestation of spondyloarthropathy. The aim of this study was to evaluate the effects of anti-IL-17 therapy on spontaneous ankylosing enthesitis in mice. In this study, we used male DBA/1 mice as a spontaneous ankylosis model.

Classification of Physiological 18F-fluorodeoxyglucose Uptake in the Large Intestine: a Preliminary Study.

Varying degrees of physiological uptake of 18F-fluorodeoxyglucose (FDG) are often noted in the large intestine and can be problematic when interpreting positron emission tomography (PET) images. In relation to colorectal tumor detection with FDG PET, we tentatively classified physiological FDG uptake in the large intestine according to its patterns and intensity. Subjects were 144 asymptomatic individuals (109 men, 35 women; mean age 57.

New BRAF knockin mice provide a pathogenetic mechanism of developmental defects and a therapeutic approach in cardio-facio-cutaneous syndrome.

Cardio-facio-cutaneous (CFC) syndrome is one of the 'RASopathies', a group of phenotypically overlapping syndromes caused by germline mutations that encode components of the RAS-MAPK pathway. Germline mutations in BRAF cause CFC syndrome, which is characterized by heart defects, distinctive facial features and ectodermal abnormalities. To define the pathogenesis and to develop a potential therapeutic approach in CFC syndrome, we here generated new knockin mice (here Braf(Q241R/+)) expressing the Braf Q241R mutation, which corresponds to the most frequent mutation in CFC syndrome, Q257R.

Epigallocatechin gallate inhibits oxidative stress-induced DNA damage and apoptosis in MRL-Fas(lpr) mice with autoimmune sialadenitis via upregulation of heme oxygenase-1 and Bcl-2.

Pathogenic effects of reactive oxygen species (ROS) in the salivary glands of patients with Sjögren's syndrome have been demonstrated. Epigallocatechin gallate (EGCG), which is a catechin derivative and exhibits potent antioxidant activity, has been reported to ameliorate autoimmune sialadenitis in a murine model, but the mechanism underlying its protective action remains to be investigated. Herein, we examined the effects of EGCG administration to MRL/MpJ-lpr/lpr (MRL-Fas(lpr)) mice on disease severity of autoimmune sialadenitis and protein expression levels of 11 sialadenitis-related molecules - heme oxygenase-1 (HO-1) (antioxidant); thymidine glycol (marker of DNA damage); gp91phox/NADPH oxidase 2 (prooxidant); single-stranded DNA (ssDNA) and cleaved caspase 3 (apoptotic cell markers); p53 and Bax (proapoptotic molecules); Bcl-2 (antiapoptotic molecule); SSA/Ro, SSB/La, and Ifi202 (autoantigens).

A novel autoantibody against ephrin type B receptor 2 in acute necrotizing encephalopathy.

Acute necrotizing encephalopathy (ANE) is characterized by symmetrical brain necrosis, suggested to be due to breakdown of the blood-brain barrier (BBB). We experienced a rare case of ANE complicated with systemic lupus erythematosus (SLE), and found that the patient's serum (V10-5) had binding activity to human umbilical vein endothelial cells (HUVECs). By SARF (Serological identification system for Autoantigens using a Retroviral vector and Flow cytometry) method using V10-5 IgG, a clone bound to V10-5 IgG was isolated.

Enhanced apoptosis by disruption of the STAT3-IκB-ζ signaling pathway in epithelial cells induces Sjögren's syndrome-like autoimmune disease.

Sjögren's syndrome (SS) is an autoimmune disease characterized by exocrinopathy that leads to dry eye and mouth. Although lymphocyte infiltration into exocrine glands and the generation of autoantibodies have been reported in SS, its pathogenic mechanism remains elusive. Here, we show that mice lacking the transcriptional regulator IκB-ζ developed SS-like inflammation characterized by lymphocyte-infiltrated dacryoadenitis and SS-associated autoantibodies.

An innovative method to identify autoantigens expressed on the endothelial cell surface: serological identification system for autoantigens using a retroviral vector and flow cytometry (SARF).

Autoantibodies against integral membrane proteins are usually pathogenic. Although anti-endothelial cell antibodies (AECAs) are considered to be critical, especially for vascular lesions in collagen diseases, most molecules identified as autoantigens for AECAs are localized within the cell and not expressed on the cell surface. For identification of autoantigens, proteomics and expression library analyses have been performed for many years with some success.

A bacterial artificial chromosome transgene with polymorphic Cd72 inhibits the development of glomerulonephritis and vasculitis in MRL-Faslpr lupus mice.

Systemic lupus erythematosus is considered to be under the control of polygenic inheritance, developing according to the cumulative effects of susceptibility genes with polymorphic alleles; however, the mechanisms underlying the roles of polygenes based on functional and pathological genomics remain uncharacterized. In this study, we substantiate that a CD72 polymorphism in the membrane-distal extracellular domain impacts on both the development of glomerulonephritis and vasculitis in a lupus model strain of mice, MRL/MpJ-Fas(lpr), and the reactivity of BCR signal stimulation. We generated mice carrying a bacterial artificial chromosome transgene originating from C57BL/6 (B6) mice that contains the Cd72(b) locus (Cd72(B6) transgenic [tg]) or the modified Cd72(b) locus with an MRL-derived Cd72(c) allele at the polymorphic region corresponding to the membrane-distal extracellular domain (Cd72(B6/MRL) tg).

Sjögren's syndrome-like autoimmune sialadenitis in MRL-Faslpr mice is associated with expression of glucocorticoid-induced TNF receptor-related protein (GITR) ligand and 4-1BB ligand.

Although costimulatory molecules have been shown to play crucial roles in the immune response, their involvement in the pathogenesis of Sjögren's syndrome is incompletely understood. In this study, we evaluated the relationship between the severity of spontaneous Sjögren's syndrome-like autoimmune sialadenitis in MRL/MpJ-lpr/lpr (MRL-Fas(lpr)) mice and the expression of 6 costimulatory molecules that play important roles in the immune response: CD80, CD86, OX40 ligand (OX40L), 4-1BB ligand (4-1BBL), glucocorticoid-induced TNF receptor-related protein ligand (GITRL), and B cell-activating factor of the tumor necrosis factor family (BAFF). Expression of the costimulatory molecules in the submandibular salivary glands of age-matched autoimmune MRL-Fas(lpr) mice and non-autoimmune MRL/MpJ-+/+(MRL/+) and C3H/HeJ-lpr/lpr (C3H-Fas(lpr)) mice was examined immunohistochemically and scored on a scale of 0 to 3.

Roles of Keap1-Nrf2 system in upper aerodigestive tract carcinogenesis.

Cancers in the upper aerodigestive tract, including cancers of the tongue and the esophagus, are the third leading cause of cancer-related deaths in the world, and oxidative stress is well recognized as one of the major risk factors for carcinogenesis. The Keap1-Nrf2 system plays a critical role in cellular defense against oxidative stress, but little is known about its association with upper aerodigestive tract carcinogenesis. In this study, we examined whether loss of Nrf2-function exacerbates carcinogenesis by using an experimental carcinogenesis model that is induced by 4-nitroquinoline-1-oxide (4NQO).

A novel autoantibody against fibronectin leucine-rich transmembrane protein 2 expressed on the endothelial cell surface identified by retroviral vector system in systemic lupus erythematosus.

Introduction: Anti-endothelial cell antibodies (AECAs) are thought to be critical for vasculitides in collagen diseases, but most were directed against molecules localized within the cell and not expressed on the cell surface. To clarify the pathogenic roles of AECAs, we constructed a retroviral vector system for identification of autoantigens expressed on the endothelial cell surface.

Methods: AECA activity in sera from patients with collagen diseases was measured with flow cytometry by using human umbilical vein endothelial cells (HUVECs).

The effect of glucagon on FDG uptake in skeletal muscle.

Glucagon is used as an anti-motility agent during gastrointestinal tract examinations. We experienced subjects with enhanced 18F-fluorodeoxyglucose (FDG) uptake in whole-body skeletal muscle when conducting positron emission tomography (PET). The subjects had been administered glucagon during gastroscopy just prior to PET.

Indispensable roles of OX40L-derived signal and epistatic genetic effect in immune-mediated pathogenesis of spontaneous pulmonary hypertension.

Background: Pulmonary hypertension (PH) refers to a spectrum of diseases with elevated pulmonary artery pressure. Pulmonary arterial hypertension (PAH) is a disease category that clinically presents with severe PH and that is histopathologically characterized by the occlusion of pulmonary arterioles, medial muscular hypertrophy, and/or intimal fibrosis. PAH occurs with a secondary as well as a primary onset.

Scattered regulatory regions of the chicken immunoglobulin-β gene and two adjacent promoters of ubiquitously expressed genes interact with the immunoglobulin-β promoter in DT40 cells.

Recent studies indicate that several transcription units assemble to form a 'transcription factory' where active transcription occurs in the nuclei. Previously, we generated chicken B-lymphocyte-derived DT40 cells lacking six transcriptional regulatory regions scattered in and around the immunoglobulin (Ig)-β gene. The deletions caused a complete shut down of transcription and epigenetic regulation of the Ig-β gene, demonstrating that the scattered regulatory regions cooperated in the transcriptional and epigenetic regulation of the gene.

Presumptive role of 129 strain-derived Sle16 locus in rheumatoid arthritis in a new mouse model with Fcγ receptor type IIb-deficient C57BL/6 genetic background.

Objective: Fcγ receptor type IIb (FcγRIIb) is a major negative regulator of B cells, and the lack of FcγRIIb expression has been reported to induce systemic lupus erythematosus (SLE) in mice of the C57BL/6 (B6) genetic background. The 129 strain-derived Sle16 locus on the telomeric region of chromosome 1 including polymorphic Fcgr2b confers the predisposition to systemic autoimmunity when present on the B6 background. We undertook this study to examine the effect of the Sle16 locus on autoimmune disease in FcγRIIb-deficient B6 mice.

Evaluation of antitumor effects following tumor necrosis factor-α gene delivery using nanobubbles and ultrasound.

The antitumor effects of tumor necrosis factor (TNF-α) were evaluated following transfection of TNF-α plasmid DNA into solid mouse tumors using the nanobubbles (NBs) and ultrasound (US) gene delivery system. Murine breast carcinoma (EMT6) cells expressing luciferase (1 × 10(6) cells) were injected intradermally into the flanks of 6-7-week-old male SCID mice on day 0. Ten microliters of TNF-α (5 μg/μL) or TNF-α mock plasmid DNA (5 μg/μL) with/without NBs (15 μL) and saline was injected intratumorally in a total volume of 30 μL, and tumors were exposed to US (frequency, 1 MHz; intensity, 3.

AMSH is required to degrade ubiquitinated proteins in the central nervous system.

Deubiquitination is a biochemical process that mediates the removal of ubiquitin moieties from ubiquitin-conjugated substrates. AMSH (associated molecule with the SH3 domain of STAM) is a deubiquitination enzyme that participates in the endosomal sorting of several cell-surface molecules. AMSH impairment results in missorted ubiquitinated cargoes in vitro and severe neurodegeneration in vivo, but it is not known how AMSH deficiency causes neuronal damage in the brain.

Prolyl isomerase pin1 protects mice from endotoxin shock.

Background: Prolyl isomerase Pin1 may be involved in innate immunity against microbial infection, but the mechanism how Pin1 controls the innate immunity is poorly understood.

Methodology/principal Findings: Injection of lipopolysaccharide (LPS) into the mice induces inflammatory pulmonary disorder and sometimes the serious damages lead to death. Comparing to the wild-type (WT) mice, the Pin1⁻/⁻ mice showed more serious damages in lung and the lower survival rate after the LPS injection.

DT40 knock-out and knock-in studies determine the regions necessary and sufficient for transcription and epigenetic conversion of the chicken Ig-β gene.

The chicken Ig-β locus is organized by three cell-type-specific genes and two ubiquitously expressed genes. B-cell-specific DNase I hypersensitive sites (DHS) in that locus, including three present inside the flanking gene, were grouped into six regions and deleted. The deletions decreased Ig-β mRNA content to <0.