Stenting with Coil Embolization for Dissecting Restenosis of the Internal Carotid Artery after Balloon Angioplasty

We report here the successful use of endovascular stenting combined with coil embolization for dissective restenosis of the internal carotid artery after balloon angioplasty. The patient was a 76-year-old man was with a history of frequent transient right hemiparesis. Angiogram showed severe stenosis in the cervical portion of both internal carotid arteries. The left lesion was treated initially by percutaneous transluminal angioplasty, which resulted in satisfactory dilatation. However, three months later, angiogram revealed restenosis and subintimal dissection at the original region. Stent implantation was performed to reconstruct the true arterial lumen, then packed the false lumen with Guglielmi detachable coils through the stent mesh. Despite anticoagulation therapy, right leg monoparesis developed two days after coiling but disappeared after a week. Nine months later, complete obliteration of the false lumen and patency of the internal carotid artery were confirmed on angiogram. This combined technique may be useful to better manage dissecting restenosis in the cervical portion of the left internal carotid artery after balloon angioplasty

Allergin-1 on mast cells suppresses house dust mite-induced airway hyperresponsiveness in mice

Although airway hyperresponsiveness (AHR) is a prominent feature of asthma, how it is regulated remains incompletely understood. Allergin-1, an inhibitory immunoglobulin-like receptor containing an immunoreceptor tyrosine-based inhibitory motif (ITIM), is expressed on human and mouse mast cells (MCs) and inhibits high-affinity receptor for IgE (FcεRI)-mediated signaling. Using MC-deficient KitW-sh/W-sh mice and Mas-TRECK mice, which carries a diphtheria toxin (DT)-induced MC deletion system based on il4 enhancer elements, we demonstrate here that MCs are involved in the induction of house dust mite (HDM)-induced AHR. Further, we show that MCs deficient in Allergin-1 exacerbated HDM-induced AHR, but had no effect on airway inflammation. In vitro analysis demonstrated that Allergin-1 inhibited anti-HDM allergen antibody-dependent HDM allergen-mediated degranulation by MCs. Thus, Allergin-1 on MCs plays an important role in the regulation of HDM-induced AHR

Differential isoform expression of Allergin-1 during acute and chronic inflammation

Introduction: Neutrophils are crucial to antimicrobial defense, but excessive neutrophilic inflammation elicits immune pathology. Currently, no effective treatment exists to curb neutrophil activation. However, neutrophils express a variety of inhibitory receptors which may represent potential therapeutic targets to limit neutrophilic inflammation. Indeed, we previously showed that the inhibitory collagen receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) regulates neutrophilic airway inflammation and inhibits neutrophil extracellular trap formation. The inhibitory receptor Allergin-1 is expressed by myeloid cells and B cells. Allergin-1 suppresses mast cell and basophil activation, but a potential regulatory role on neutrophils remains unexplored. We aimed to demonstrate the regulation of neutrophils by Allergin-1. Methods: We examine Allergin-1 isoform expression on human neutrophils during homeostatic (healthy donors) and chronic inflammatory (systemic lupus erythematosus patients) conditions in comparison to other circulating leukocytes by flow cytometry. To reveal a potential role for Allergin-1 in regulating neutrophilic inflammation, we experimentally infect wild-type (WT) and Allergin-1-deficient mice with a respiratory syncytial virus (RSV) and monitor disease severity and examine cellular airway infiltrate. Flow cytometry was used to confirm Allergin-1 expression by airway-infiltrated neutrophils in RSV infection-induced bronchiolitis patients. Results: Only the short 1 (S1) isoform, but not the long (L) or S2 isoform could be detected on blood leukocytes, with the exception of nonclassical monocytes, which exclusively express the S2 isoform. Allergin-1 expression levels did not vary significantly between healthy individuals and patients with the systemic inflammatory disease on any interrogated cell type. Airway-infiltrated neutrophils of pediatric RSV bronchiolitis patients were found to express Allergin-1S1. However, Allergin-1-deficient mice experimentally infected with RSV did not show exacerbated disease or increased neutrophil airway infiltration compared to WT littermates. Conclusion: Allergin-1 isoform expression is unaffected by chronic inflammatory conditions. In stark contrast to fellow inhibitory receptor LAIR-1, Allergin-1 does not regulate neutrophilic inflammation in a mouse model of RSV bronchiolitis

Allergin-1 inhibits TLR2-mediated mast cell activation and suppresses dermatitis

TLR2 recognizes cell wall components of Staphylococcus aureus, which colonizes >90% of atopic eczematous skin lesions. The regulatory mechanisms of TLR2 signaling in the skin remain unclear. Allergin-1, an inhibitory immunoglobulin-like receptor containing an ITIM, is expressed on mast cells (MCs) and inhibits IgE-mediated anaphylaxis in mice. Here, we show that Allergin-1 inhibits TLR2-mediated activation of, and inflammatory cytokine production by, MCs in vitro. Compared with wild-type mice, Allergin-1-deficient mice showed enhanced ear swelling with enhanced collagen deposition and greater Ly6G+ neutrophil recruitment after intra-dermal injection of Pam2CSK4 into pinnae. Using Mas–TRECK mice, which is an MC deletion system based on il4 enhancer elements, we also demonstrated that Allergin-1 on MCs is responsible for the Pam2CSK4-induced ear swelling. These results suggest that Allergin-1 on skin MCs suppresses TLR2-induced dermatitis

Functional annotation of human long noncoding RNAs via molecular phenotyping

Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-todate lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.Peer reviewe

Heterodimeric particle assemblies: Preparation of anisotropically connected spherical silica particles via surface-bound gold nanoparticles

Assemblies of heterodimeric particles were prepared through selective coupling of two kinds of spherical silica particles of different sizes by connection with gold nanoparticles attached anisotropically to the particles