Fibroblasts as Local Immune Modulators in Ocular Allergic Disease

ABSTRACTVernal keratoconjunctivitis (VKC), a severe form of ocular allergic disease, is characterized by the formation of giant papillae at the upper tarsal conjunctiva and corneal lesions that threaten vision. Recent evidence indicates that resident fibroblasts function as immune modulators in the pathogenesis of the chronic allergic inflammation associated with VKC. The T helper 2 (Th2) cell-derived cytokines interleukin (IL)-4 and IL-13 stimulate the migration and proliferation of conjunctival fibroblasts as well as protecting these cells from apoptotic cell death, effects that likely underlie the hyperplasia of fibroblasts that contributes to the formation of giant papillae. Conjunctival fibroblasts also synthesize extracellular matrix proteins and tissue inhibitors of metalloproteinases as well as down-regulate the expression of matrix metalloproteinases in response to these cytokines, effects that likely contribute to the excessive deposition of extracellular matrix that is characteristic of giant papillae. Stimulation of fibroblasts in the corneal stroma with the combination of a proinflammatory cytokine and either IL-4 or IL-13 results in up-regulation of the expression of the chemokine eotaxin and thymus- and activation-regulated chemokine as well as of vascular cell adhesion molecule-1, which together mediate the infiltration and activation of eosinophils and Th2 cells. Fibroblasts therefore appear to play a central role in the induction and amplification of ocular allergic inflammation and the consequent development of giant papillae and corneal disorders in individuals with VKC. Fibroblasts and fibroblast-derived factors thus represent new and potentially important therapeutic targets for treatment of the giant papillae and corneal disorders associated with VKC

The Quiescent Cellular State is Arf/p53-Dependent and Associated with H2AX Downregulation and Genome Stability

Cancer is a disease associated with genomic instability and mutations. Excluding some tumors with specific chromosomal translocations, most cancers that develop at an advanced age are characterized by either chromosomal or microsatellite instability. However, it is still unclear how genomic instability and mutations are generated during the process of cellular transformation and how the development of genomic instability contributes to cellular transformation. Recent studies of cellular regulation and tetraploidy development have provided insights into the factors triggering cellular transformation and the regulatory mechanisms that protect chromosomes from genomic instability

ARBUSCULAR MYCORRHIZAS IN THE ROOTS OF AFZELIA AFRICANA, ENTADA AFRICANA, AND PTEROCARPUS ERINACEUS

Afzelia africana, Entada africana, and Pterocarpus erinaceus are economically important tropical tree species in Africa. In this study, we performed morphological and molecular analyses to examine the mycorrhizal status of these species in their natural habitat in Benin, West Africa. Fine roots were examined using trypan blue staining. Putative arbuscular mycorrhizal fungi (AMF) were identified by extracting root DNA and sequencing the large subunit region of ribosomal DNA. Operational taxonomic units (OTUs) were positioned on a consensus phylogenetic tree produced using maximum likelihood and neighbor-joining models. Morphological analyses revealed vesicles, arbuscules, and inter- and intracellular hyphae in roots of all three tree species. Molecular analyses revealed 39 AMF OTUs, among which 18 were from roots of E. africana, 15 from P. erinaceus, and 9 from A. africana. These OTUs belonged to Glomus, Nanoglomus, Rhizoglomus, Sclerocystis, Septoglomus, and Scutellospora; two unidentified species belonged to the family Glomeraceae. This is the first study to report AMF in roots of A. africana, E. africana, and P. erinaceus in Benin, and opens new avenues for future studies.Peer reviewe

Azilsartan, an angiotensin II type 1 receptor blocker, restores endothelial function by reducing vascular inflammation and by increasing the phosphorylation ratio Ser1177/Thr497 of endothelial nitric oxide synthase in diabetic mice

BACKGROUND: Azilsartan, an angiotensin II type 1 (AT1) receptor blocker (ARB), has a higher affinity for and slower dissociation from AT1 receptors and shows stronger inverse agonism compared to other ARBs. Possible benefits of azilsartan in diabetic vascular dysfunction have not been established. METHODS: We measured vascular reactivity of aortic rings in male KKAy diabetic mice treated with vehicle, 0.005% azilsartan, or 0.005% candesartan cilexetil for 3 weeks. Expression of markers of inflammation and oxidative stress was measured using semiquantitative RT-PCR in the vascular wall, perivascular fat, and skeletal muscle. Phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser(1177) and Thr(495) was measured using Western blotting, and the ratio of phosphorylation at Ser(1177) to phosphorylation at Thr(495) was used as a putative indicator of vascular eNOS activity. RESULTS: (1) Vascular endothelium–dependent relaxation with acetylcholine in KKAy mice was improved by azilsartan treatment compared to candesartan cilexetil; (2) the ratio of Ser(1177)/Thr(495) phosphorylation of eNOS was impaired in KKAy and was effectively restored by azilsartan; (3) anomalies in the expression levels of monocyte chemotactic protein 1 (MCP1), F4/80, NAD(P)H oxidase (Nox) 2, and Nox4 of the aortic wall and in the expression of TNFα in the perivascular fat were strongly attenuated by azilsartan compared to candesartan cilexetil. CONCLUSIONS: These results provide evidence that azilsartan prevents endothelial dysfunction in diabetic mice, more potently than does candesartan cilexetil. Azilsartan’s higher affinity for and slower dissociation from AT1 receptors may underlie its efficacy in diabetic vascular dysfunction via a dual effect on uncoupled eNOS and on Nox

Time and Composition Dependent Electrical Conductivity of Vanadate Glasses Showing Both Cationic Conduction and Electronic Conduction

Silver vanadate glasses show electrical conductivity higher than 10–2 S cm–1, caused by the electron hopping from VIV to VV together with an ionic conduction due to Ag+. Lithium vanadate glasses show electrical conductivity of the order of 10–6 S cm–1 which is primarily due to an electron hopping from VIV to VV. Fraction of the Ag+ or Li+ conduction and that of electron hopping from VIV to VV can be estimated by measuring both AC- and DC-conductivities. The latter becomes saturated after 50 min or more due to polarization of the mobile Ag+ or Li+ ions at around the cathode

予算スラックと日本的予算管理

本稿は、予算スラックを切り口に、日本的予算管理の特徴を説明するフレームワークを提示することを目的としている。比較ケース・スタディのために行われた、日本企業4社へのインタビュー調査からの知見に基づき、日本企業における予算管理では、事前統制と期中統制の段階において、インターラクションと情報共有を高めるさまざまな仕組みが機能しており、結果的に予算スラックを低水準に保っていること、また事後統制段階においても、予算業績と報酬との弱いリンクによってストレッチな予算目標の設定を可能にし、結果的に予算スラックを低水準に抑制していることなどを明らかにした。さらに、カルチャーや制度といった要因も日本企業の予算管理実務を説明する上で看過できない重要なファクターであることを併せて示している