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[PMID]: 23600606
[Au] Autor:Hargis AM; Myers S; Gortel K; Duclos D; Randolph-Habecker J
[Ad] Address:DermatoDiagnostics, Edmonds, WA, 98026, USA; Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA, 98195, USA.
[Ti] Title:Proliferative, lymphocytic, infundibular mural folliculitis and dermatitis with prominent follicular apoptosis and parakeratotic casts in four Labrador retrievers: preliminary description and response to therapy.
[So] Source:Vet Dermatol;24(3):346-e77, 2013 Jun.
[Is] ISSN:1365-3164
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:OBJECTIVES: To describe the clinical, histopathological and immunohistochemical lesions and the response to therapy of a novel skin disease in four dogs, and to compare the lesions with those of other similar conditions. METHODS: Clinical lesions, the histopathological findings in skin biopsy samples, immunohistochemistry for CD3 and cleaved caspase-3 and the response to therapy were evaluated. RESULTS: Clinical lesions included multifocal, coalescing, verrucous, crusted papules and plaques with erythematous borders and comedones or follicular casts. Lesions were in haired skin; they occurred at the edges of paw pads and claw beds in one dog. Histopathological lesions included ortho- and more prominent parakeratotic hyperkeratosis involving follicular infundibular epithelium, with cast formation and a papillary epidermal surface. Lymphocytic exocytosis affected all strata of follicular infundibular epithelium and epidermis. Variable numbers of acidophilic shrunken keratinocytes, often bordered by lymphocytes (satellitosis), occupied the more superficial strata of the follicular infundibular epithelium and epidermis. Immunohistochemistry revealed numerous CD3+ T lymphocytes and fewer cleaved caspase-3-positive apoptotic keratinocytes in the infundibular hair follicle epithelium and epidermis, with numerous CD3+ T lymphocytes and cleaved caspase-3-positive cells in the dermis. Two dogs responded completely to therapy with ciclosporin and remained lesion free off therapy; one dog responded to therapy with prednisone, azathioprine and ciclosporin, but relapsed; and one dog was not treated. CONCLUSIONS AND CLINICAL IMPORTANCE: The cause of the lesions is unknown; the presence of intraepithelial CD3+ lymphocytes and cleaved caspase-3-positive apoptotic keratinocytes and the positive response to immunosuppressive therapy suggest an immune response directed towards unidentified antigens expressed on the surface of keratinocytes.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1305
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1111/vde.12022

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[PMID]: 23117587
[Au] Autor:Kimura W; Sharkar MT; Sultana N; Islam MJ; Uezato T; Miura N
[Ad] Address:Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu, 431-3192, Shizuoka, Japan.
[Ti] Title:Generation and characterization of Tbx1-AmCyan1 transgenic reporter mouse line that selectively labels developing thymus primordium.
[So] Source:Transgenic Res;22(3):659-66, 2013 Jun.
[Is] ISSN:1573-9368
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Thymus development is a complicated process that includes highly dynamic morphological changes and reciprocal tissue interactions between endoderm-derived epithelial cells of the anterior foregut and neural crest-derived mesenchymal cells. We generated and characterized a Tbx1-AmCyan1 reporter transgenic mouse to visualize thymus precursor cells during early embryonic development. In transgenic embryos, AmCyan1 fluorescence was specifically detected in the endoderm of the developing 3rd and 4th pharyngeal pouches and later in thymus epithelium until E14.5. Cells expressing AmCyan1 that were isolated based on AmCyan1 fluorescence expressed endodermal, thymic, and parathyroid markers, but they did not express neural crest or endothelial markers; these findings indicated that this transgenic mouse strain could be used to collect thymic or parathyroid precursor cells or both. We also showed that in nude mice, which exhibit defects in thymus development, the thymus precursors were clearly labeled with AmCyan1. In summary, these AmCyan1-fluorescent transgenic mice are useful for investigating early thymus development.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1305
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1007/s11248-012-9664-5

  3 / 239035 MEDLINE  
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[PMID]: 23671562
[Au] Autor:Parker JC; Thavagnanam S; Skibinski G; Lyons J; Bell J; Heaney LG; Shields MD
[Ad] Address:Centre for Infection and Immunity, Queen's University Belfast, Belfast, Northern Ireland.
[Ti] Title:Chronic IL9 and IL-13 Exposure Leads to an Altered Differentiation of Ciliated Cells in a Well-Differentiated Paediatric Bronchial Epithelial Cell Model.
[So] Source:PLoS One;8(5):e61023, 2013.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Asthma is a chronic inflammatory disease characterised by airways remodelling. In mouse models IL-9 and IL-13 have been implicated in airways remodelling including mucus hypersecretion and goblet cell hyperplasia. Their role, especially that of IL-9, has been much less studied in authentic human ex vivo models of the bronchial epithelium from normal and asthmatic children. We assessed the effects of IL-9, IL-13 and an IL-9/IL-13 combination, during differentiation of bronchial epithelial cells from normal (n = 6) and asthmatic (n = 8) children. Cultures were analysed for morphological markers and factors associated with altered differentiation (MUC5AC, SPDEF and MMP-7). IL-9, IL-9/IL-13 combination and IL-13 stimulated bronchial epithelial cells from normal children had fewer ciliated cells [14.8% (SD 8.9), p = 0.048, 12.4 (SD 6.1), p = 0.016 and 7.3% (SD 6.6), p = 0.031] respectively compared with unstimulated [(21.4% (SD 9.6)]. IL-9 stimulation had no effect on goblet cell number in either group whereas IL-9/IL-13 combination and IL-13 significantly increased goblet cell number [24.8% (SD 8.8), p = 0.02), 32.9% (SD 8.6), p = 0.007] compared with unstimulated normal bronchial cells [(18.6% (SD 6.2)]. All stimulations increased MUC5AC mRNA in bronchial epithelial cells from normal children and increased MUC5AC mucin secretion. MMP-7 localisation was dysregulated in normal bronchial epithelium stimulated with Th2 cytokines which resembled the unstimulated bronchial epithelium of asthmatic children. All stimulations resulted in a significant reduction in transepithelial electrical resistance values over time suggesting a role in altered tight junction formation. We conclude that IL-9 does not increase goblet cell numbers in bronchial epithelial cell cultures from normal or asthmatic children. IL-9 and IL-13 alone and in combination, reduce ciliated cell numbers and transepithelial electrical resistance during differentiation of normal epithelium, which clinically could inhibit mucociliary clearance and drive an altered repair mechanism. This suggests an alternative role for IL-9 in airways remodelling and reaffirms IL-9 as a potential therapeutic target.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1305
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0061023

  4 / 239035 MEDLINE  
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[PMID]: 23483557
[Au] Autor:Marsh V; Davies EJ; Williams GT; Clarke AR
[Ad] Address:Cardiff School of Biosciences, Cardiff University, UK.
[Ti] Title:PTEN loss and KRAS activation cooperate in murine biliary tract malignancies.
[So] Source:J Pathol;230(2):165-73, 2013 Jun.
[Is] ISSN:1096-9896
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Carcinomas of the biliary tract are aggressive malignancies in humans. Loss of the tumour suppressor PTEN has previously been associated with cholangiocarcinoma development in a murine model. Activation of KRAS is reported in up to one-third of human cholangiocarcinomas and 50% of gall bladder carcinomas. In this study we aimed to test the potential interaction between PTEN and KRAS mutation in biliary tract malignancy. We used an inducible Cre-LoxP-based approach to coordinately delete PTEN and activate KRAS within the adult mouse biliary epithelium. We found that activation of KRAS alone has little effect upon biliary epithelium. Loss of PTEN alone results in the development of low-grade neoplastic lesions, following long latency and at low incidence. Combination of both mutations causes rapid development of biliary epithelial proliferative lesions, which progress through dysplasia to invasive carcinoma. We conclude that activation of the PI3'K pathway following loss of PTEN is sufficient to drive slow development of low-grade biliary lesions in mice. In contrast, mutational activation of KRAS does not result in a similar phenotype, despite a prediction that this should activate both the RAF-MEK-ERK and PI3'-kinase pathways. However, mutation of both genes results in rapid tumourigenesis, arguing that PTEN normally functions as a 'brake' on the PI3'-kinase pathway, limiting the influence of KRAS activation. Mutation of both genes creates a 'permissive' environment, allowing the full effects of both mutations to be manifested. These data reveal an in vivo synergy between these mutations and provides a new mouse model of biliary tract malignancy. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1305
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1002/path.4189

  5 / 239035 MEDLINE  
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[PMID]: 23583634
[Au] Autor:Robitaille M; Shi J; McBride S; Wan KT
[Ad] Address:Bioengineering, Northeastern University, Boston, MA 02115, United States.
[Ti] Title:Mechanical performance of hydrogel contact lenses with a range of power under parallel plate compression and central load.
[So] Source:J Mech Behav Biomed Mater;22:59-64, 2013 Jun.
[Is] ISSN:1878-0180
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:When a contact lens is compressed between two parallel plates (PPC) or under a central load (CLC), the constitutive relation depends not only on the mechanical properties such as elastic modulus, E, of the hydrogel materials, but also the lens power, d, or thickness variation, h(ϕ0), along the meridional direction ϕ0. Hyperopic lenses (d>0) are thicker at the apex along the optical axis and thin out gradually along the meridian, while myopic lenses (d<0) are thinnest at the apex. Mechanical deformation is quantified by the inter-relationship between applied force, F, vertical displacement of the external load, w0, contact or dimple radius, a, and the deformed profile, w(r). Force responses show that lenses with positive d are apparently stiffer in the initial loading but become more compliant as load increases. Conversely, lenses with negative d are more deformable initially and becomes gradually more resistant to loading. This is consistent with the theoretical shell model using the same E. The mechanical behavior has significant impacts in defining the degree of comfort of contact lenses as well as the lens adhesion to the corneal epithelium.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1305
[Js] Journal subset:IM
[St] Status:In-Data-Review

  6 / 239035 MEDLINE  
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[PMID]: 23424199
[Au] Autor:Yan S; Lv Z; Winterhoff M; Wenzl C; Zobel T; Faix J; Bogdan S; Grosshans J
[Ad] Address:Institut für Biochemie, Universitätsmedizin, Universität Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen, Germany.
[Ti] Title:The F-BAR protein Cip4/Toca-1 antagonizes the formin Diaphanous in membrane stabilization and compartmentalization.
[So] Source:J Cell Sci;126(Pt 8):1796-805, 2013 Apr 15.
[Is] ISSN:1477-9137
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:During Drosophila embryogenesis, the first epithelium with defined cortical compartments is established during cellularization. Actin polymerization is required for the separation of lateral and basal domains as well as suppression of tubular extensions in the basal domain. The actin nucleator mediating this function is unknown. We found that the formin Diaphanous (Dia) is required for establishing and maintaining distinct lateral and basal domains during cellularization. In dia mutant embryos lateral marker proteins, such as Discs-large and Armadillo/ß-Catenin spread into the basal compartment. Furthermore, high-resolution and live-imaging analysis of dia mutant embryos revealed an increased number of membrane extensions and endocytic activity at the basal domain, indicating a suppressing function of dia on membrane invaginations. Dia function might be based on an antagonistic interaction with the F-BAR protein Cip4/Toca-1, a known activator of the WASP/WAVE-Arp2/3 pathway. Dia and Cip4 physically and functionally interact and overexpression of Cip4 phenocopies dia loss-of-function. In vitro, Cip4 inhibits mainly actin nucleation by Dia. Thus, our data support a model in which linear actin filaments induced by Dia stabilize cortical compartmentalization by antagonizing membrane turnover induced by WASP/WAVE-Arp2/3.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1305
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1242/jcs.118422

  7 / 239035 MEDLINE  
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[PMID]: 23406873
[Au] Autor:Shi Y; Gong B; Chen L; Zuo X; Liu X; Tam PO; Zhou X; Zhao P; Lu F; Qu J; Sun L; Zhao F; Chen H; Zhang Y; Zhang D; Lin Y; Lin H; Ma S; Cheng J; Yang J; Huang L; Zhang M; Zhang X; Pang CP; Yang Z
[Ad] Address:These authors contributed equally to this work.
[Ti] Title:A genome-wide meta-analysis identifies two novel loci associated with high myopia in the Han Chinese population.
[So] Source:Hum Mol Genet;22(11):2325-33, 2013 Jun 1.
[Is] ISSN:1460-2083
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:High myopia, highly prevalent in the Chinese population, is a leading cause of visual impairment worldwide. Genetic factors play a critical role in the development of this visual disorder. Genome-wide association studies in recent years have revealed several chromosomal regions that contribute to its progression. To identify additional genetic variants for high myopia susceptibility, we used a genome-wide meta-analysis to examine the associations between the disease and 286 031 single-nucleotide polymorphisms (SNPs) in a combined cohort of 665 cases and 960 controls. The most significant SNPs (n = 61) were genotyped in a replication cohort (850 cases and 1197 controls), and 14 SNPs were further tested through genotyping in two additional validation cohorts (combined 1278 cases and 2486 controls). As a result of this analysis, four SNPs reached genome-wide significance (P < 2.0 × 10(-7)). The most significantly associated SNP, rs2730260 [overall P = 8.95 × 10(-14); odds ratio (95% CI) =1.33 (1.23-1.44)], is located in the VIPR2 gene, which is located in the MYP4 locus. The other three SNPs (rs7839488, rs4395927 and rs4455882) in the same linkage disequilibrium block are located in the SNTB1 gene, with -P values ranging from 1.13 × 10(-8) to 2.13 × 10(-11). The VIPR2 and SNTB1 genes are expressed in the retina and the retinal pigment epithelium and have been previously reported to have potential functions for the pathogenesis of myopia. Our results suggest that variants of the VIPR2 and SNTB1 genes increase susceptibility to high myopia in Han Chinese.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1305
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1093/hmg/ddt066

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[PMID]: 23633672
[Au] Autor:Royet J; Charroux B
[Ad] Address:Aix-Marseille Université; CNRS; Institut de Biologie du Développement de Marseille-Luminy UMR CNRS 7288; Marseille, France.
[Ti] Title:Mechanisms and consequence of bacteria detection by the Drosophila gut epithelium.
[So] Source:Gut Microbes;4(3):259-63, 2013 May 1.
[Is] ISSN:1949-0984
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Since insect mostly developed on decaying matter and contaminated fruits, they are constantly ingesting bacteria. The insect model, Drosophila, is therefore well adapted to study the interactions that take place between the gut epithelia and either resident or infectious bacteria. In order to provide an ad hoc immune response, gut epithelial cells must detect the presence of bacteria. In a recent report, Bosco-Drayon et al. identify the main receptors by which Drosophila sense gut associated bacteria and analyze how this bacteria-receptor interaction translate into gene activation.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1305
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.4161/gmic.24386

  9 / 239035 MEDLINE  
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[PMID]: 23549027
[Au] Autor:Lapthorne S; Pereira-Fantini PM; Fouhy F; Wilson G; Thomas SL; Dellios NL; Scurr M; O'Sullivan O; Ross RP; Stanton C; Fitzgerald GF; Cotter PD; Bines JE
[Ad] Address:Intestinal Failure and Clinical Nutrition Group; Murdoch Childrens Research Institute; Parkville, Australia; Teagasc Food Research Centre; Moorepark; Fermoy, Ireland; Department of Microbiology; University College Cork; Cork, Ireland; Alimentary Pharmabiotic Centre; University College Cork; Cork, Ireland; Department of Paediatrics; University of Melbourne; Parkville, Australia; Department of Gastroenterology and Clinical Nutrition; Royal Children's Hospital; Parkville, Australia.
[Ti] Title:Gut microbial diversity is reduced and is associated with colonic inflammation in a piglet model of short bowel syndrome.
[So] Source:Gut Microbes;4(3):212-21, 2013 May 1.
[Is] ISSN:1949-0984
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Background and objectives: Following small bowel resection (SBR), the luminal environment is altered, which contributes to clinical manifestations of short bowel syndrome (SBS) including malabsorption, mucosal inflammation and bacterial overgrowth. However, the impact of SBR on the colon has not been well-defined. The aims of this study were to characterize the colonic microbiota following SBR and to assess the impact of SBR on mucosal inflammation in the colon.   Results Analysis of the colonic microbiota demonstrated that there was a significant level of dysbiosis both two and six weeks post-SBR, particularly in the phylum Firmicutes, coupled with a decrease in overall bacterial diversity in the colon. This decrease in diversity was associated with an increase in colonic inflammation six weeks post-surgery. Methods Female (4-week old) piglets (5-6/group) received a 75% SBR, a transection (sham) or no surgery. Compositional analysis of the colonic microbiota was performed by high-throughput sequencing, two- and six-weeks post-surgery. The gene expression of the pro-inflammatory cytokines interleukin (IL)-1ß, IL-6, IL-8, IL-18 and tumor necrosis factor (TNF)-α in the colonic mucosa was assessed by qRT-PCR and the number of macrophages and percentage inducible nitric oxide synthase (iNOS) staining in the colonic epithelium were quantified by immunohistochemistry. Conclusions SBR significantly decreased the diversity of the colonic microbiota and this was associated with an increase in colonic mucosal inflammation. This study supports the hypothesis that SBR has a significant impact on the colon and that this may play an important role in defining clinical outcome.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1305
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.4161/gmic.24372

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[PMID]: 23542685
[Au] Autor:Grootjans J; Hundscheid IH; Buurman WA
[Ad] Address:Department of Internal Medicine; Slotervaartziekenhuis; Amsterdam, the Netherlands; Department of Surgery; NUTRIM School for Nutrition, Toxicology & Metabolism; Maastricht University Medical Centre; Maastricht, the Netherlands; NUTRIM School for Nutrition, Toxicology & Metabolism; Maastricht University Medical Centre; Maastricht, the Netherlands.
[Ti] Title:Goblet cell compound exocytosis in the defense against bacterial invasion in the colon exposed to ischemia-reperfusion.
[So] Source:Gut Microbes;4(3):232-5, 2013 May 1.
[Is] ISSN:1949-0984
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:In recent years, the importance of the mucus layer in the colon has become increasingly clear. Disturbance of the mucus layer has been implicated in a variety of intestinal diseases. We have recently investigated the importance of the mucus layer in colon ischemia-reperfusion (IR). Using a newly developed human and rat colon IR model, we showed that colon ischemia leads to mucus barrier breakdown. This allowed intraluminal bacteria to interact with the colonic epithelium, which was associated with an inflammatory response. Intriguingly, we found goblet cells to respond immediately by expelling their mucin granules into the gut lumen, which flushed bacteria from the colonic crypts and resulted in rapid restoration of the mucus layer during reperfusion. Our study might explain why ischemic colitis tends to have favorable outcomes and can often be treated conservatively.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1305
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.4161/gmic.23866


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