IL-33 attenuates the development of experimental autoimmune uveitis

Interleukin (IL)-33 is associated with several important immune-mediated disorders. However, its role in uveitis, an important eye inflammatory disease, is unknown. Here we investigated the function of IL-33 in the development of experimental autoimmune uveitis (EAU). IL-33 and IL-33 receptor (ST2) were expressed in murine retinal pigment epithelial (RPE) cells in culture, and IL-33 increased the expression of Il33 and Mcp1 mRNA in RPE cells. In situ, IL-33 was highly expressed in the inner nuclear cells of the retina of naïve mice, and its expression was elevated in EAU mice. ST2-deficient mice developed exacerbated EAU compared with WT mice, and administration of IL-33 to WT mice significantly reduced EAU severity. The attenuated EAU in IL-33-treated mice was accompanied by decreased frequency of IFN-γ(+) and IL-17(+) CD4(+) T cells and reduced IFN-γ and IL-17 production but with increased frequency of IL-5(+) and IL-4(+) CD4 T cells and IL-5 production in the draining lymph node and spleen. Macrophages from the IL-33-treated mice show a significantly higher polarization towards an alternatively-activated macrophage (M2) phenotype. Our results therefore demonstrate that the endogenous IL-33/ST2 pathway plays an important role in EAU, and suggest that IL-33 represents a potential option for treatment of uveitis.

Expression of toll-like receptors by human muscle cells in vitro and in vivo:TLR3 is highly expressed in inflammatory and HIV myopathies, mediates IL-8 release and up-regulation of NKG2D-ligands

The particular microenvironment of the skeletal muscle can be the site of complex immune reactions. Toll-like receptors (TLRs) mediate inflammatory stimuli from pathogens and endogenous danger signals and link the innate and adaptive immune system. We investigated innate immune responses in human muscle. Analyzing TLR1-9 mRNA in cultured myoblasts and rhabdomyosarcoma cells, we found constitutive expression of TLR3. The TLR3 ligand Poly (I:C), a synthetic analog of dsRNA, and IFN-gamma increased TLR3 levels. TLR3 was mainly localized intracellularly and regulated at the protein level. Poly (I:C) challenge 1) activated nuclear factor-kappaB (NF-kappaB), 2) increased IL-8 release, and 3) up-regulated NKG2D ligands and NK-cell-mediated lysis of muscle cells. We examined muscle biopsy specimens of 6 HIV patients with inclusion body myositis/polymyositis (IBM/PM), 7 cases of sporadic IBM and 9 nonmyopathic controls for TLR3 expression. TLR3 mRNA levels were elevated in biopsy specimens from patients with IBM and HIV-myopathies. Muscle fibers in inflammatory myopathies expressed TLR3 in close proximity of infiltrating mononuclear cells. Taken together, our study suggests an important role of TLR3 in the immunobiology of muscle, and has substantial implications for the understanding of the pathogenesis of inflammatory myopathies or therapeutic interventions like vaccinations or gene transfer.

The Double Life of Duke of Somerset v Cookson, or a Legal Excavation of the Corbridge Lanx

Duke of Somerset v Cookson (1735) occupies an important place in English legal history as a leading authority for Chancery jurisdiction to order specific delivery of movable property where an award of damages would be inadequate. The property at issue was the Corbridge lanx, now in the British Museum, but then claimed as treasure trove by the duke of Somerset as lord of the manor of Corbridge. This paper re-examines Cookson as the first reported English decision relating to treasure trove, and uses later treasure trove claims by the duke of Somerset's successors to the manor of Corbridge, the dukes of Northumberland, to shed fresh light on the 1735 decision and on the development of treasure trove practice from the eighteenth century onwards.

Poem translation: 'How Many Shady Abodes'. Host publication: 'Il filo della vita-The thread of life-Snáithe na beatha' (ed. A. Gentili)

Poem

Acute flare induced by the calcific tendonitis of the rotator cuff: inhibition of IL-1 a potential therapeutic target?

Introduction: Calcific tendonitis of rotator cuff is observed on plainradiographs in 10% of adults, but remains asymptomatic in half thesecases. Sometimes, these calcifications induce acute flares withmassive inflammation similar to gout or CPPD crisis. Analgesics/anti-inflammatory medications are usually not sufficient to controlssymptoms in these situations. Local steroid infiltration with or withoutremoval of the calcific deposition with a needle aspiration may beuseful. A new approach could be IL-1 inhibitors. Indeed, basic calciumphosphate crystals are capable of stimulating the release of activeIL-1β in vitro. These crystals trigger IL-1β release, in an analogousmanner to MSU crystals in acute gout, suggesting that IL-1β blockademay be clinically useful.Case presentation: This report describes a 70-year old woman withacute rest pain of the right shoulder since 48 hours. On examination,we found massive limitations of active and passive movements. Thepatient evaluated, on the visual scale, her symptoms at 10/10 the nightand 5/10 the day. The radiography and showed a rounded, 8 mmcalcification in the subscapularis tendon. The ultrasound aspectrevealed a heterogeneous calcification partially non solid, surroundedby massive inflammation on Doppler. C-reactive protein anderythrocyte sedimentation rate were high (74 mg/ml, 54 mm/hour).The patient received subcutaneous injections of anakinra: 100 mgdaily for 3 days (D1-D3). We evaluated the patient in our consult at dayD1, D2, D3, D7, D16 and by phone at D70.This treatment rapidly relieved the inflammatory symptoms (within afew hours with no relapse). The mobility of the shoulder, the biologicsparameters improved and the size of the calcification as well thedegree of inflammation regressed on ultrasound after 3 days.Conclusion: This is the first report of a woman with an acute flareinduced by calcific tendonitis who received anakinra. IL-1 inhibitionmay be a therapeutic target in calcific tendonitis. To analyse thisresponse more precisely and elaborate definitive conclusions, aprospective pilot study is on-going in our ambulatory institute.

HCV infection after liver transplantation is associated with lower levels of alloreactive CD4+CD25+CD45RO+IL-7R+high+ T cells

Aim: Expression of IL-7R discriminates alloreactive CD4 T cells (Foxp3 negative), from IL-7Rlow regulatory CD4 T cells (Foxp3 positive). Chronic hepatitis C virus infection (HCV) reduces expression of IL-7R on T cells thus promoting persistence of infection. The aim of this study was to analyze the effect of HCV infection on the expression of IL-7R of activated CD4+ T cells in liver transplant patients. Patients and methods: We analyzed PBMC from liver transplant recipients for the expression of CD4, CD25, FoxP3, IL-7R (24 HCV negative and 29 HCV-chronically infected). We compared these data with non-transplanted individuals (52 HCV-chronically infected patients and 38 healthy donors). Results: In HCV-infected liver transplant recipients, levels of CD4+CD25+CD45RO+IL-7R+ T cells were significantly reduced (10.5+/-0.9%) when compared to non-HCV-infected liver transplant recipients (17.6+/-1.4%) (P<0.001), while both groups (HCV-infected and negative transplant recipients) had significantly higher levels than healthy individuals (6.6+/-0.9%) (P<0.0001). After successful antiviral therapy (sustained antiviral response), 6 HCV-infected transplant recipients showed an increase of CD4+CD25+CD45RO+IL-7R+ T cells, reaching levels similar to that of non-HCVinfected recipients (10.73+/-2.63% prior therapy versus 21.7+/-6.3% after clearance of HCV). (P<0.05) In 4 non-responders (i.e. HCVRNA remaining present in serum), levels of CD4+CD25+CD45RO+IL-7R+ T cells remained unmodified during and after antiviral treatment (11.8+/- 3.3% versus 11.3+/-3.3% respectively). Conclusions: Overall, these data indicate that CD4+CD25+CD45RO+IL-7R+ T cells appear to be modulated by chronic HCV infection after liver transplantation. Whether lower levels of alloreactive T cells in HCV-infected liver transplant recipients are associated with a tolerogenic profile remains to be studied.

The dominions of the Czar of Russia Alba or Great Duke of Moscovia in which are the Dukedoms of Moscow, Wolodimer, Rezan, Worotin, Novogorod-Sewierski, Czernihow, Smolensko, Reschow, Twer, Novogorod-Weliki, Biele Jezora, Wologda, .. /

1 kartta :, käsinvär. ;, 57 x 88 cm, lehti 62,5 x 92,5 cm

Compendio di gesti del magnanimo et gloriosissimo Signore Sforza, inc[ipiente] dal tempo de la sua natiuità fine a la morte sua, compiliato in vulgare per Antonio Placentino nel anne MCCCCLVIII in Milano sotto lo Illustrissimo Signore Francesco Sforza Duca Duca quarto. (In fine: " Bartholomeus Gambagnola Cremonensis scripsit mandato Mag[nifi]ci domini Marchisini stanghe ducalis secretarii Die uigesimo septembris MCCCCLXXXX primo ". Membran. Con finissime miniature a f. 1 e 5. Il f. 4 è occupato da una mirabile miniatura rappresentante un guerriero a cavallo; sotto, leggesi: " Sfortia Atendolus italicorum ducum clarissimus ". Il suo ritratto è miniato anche a f. 5: nel margine inferiore della prima pagina è quello di Francesco Sforza. Nel corpo del testo molte lettere iniziali sono miniate).

Visconti. Saisi par Louis XII dans la bibliothèque des ducs de Milan à Pavie . N° 1466 du catalogue de 1544 et cote "Des vulgaires italiens pulpito 1°" de la Librairie royale de Blois ; — n° 2826 du catalogue de la Bibliothèque du roi à Paris à la fin du XVIe s.

I.O.D.E. Duke of Kent Chapter Fonds, 1934-1980

The I.O.D.E. as we currently know it today was founded in 1900 by Margaret Polson Murray of Montreal, who recognized a need for loyal support of Canadians departing to fight in the Boer War with the Empire forces in South Africa. She encouraged the formation of a federation of women to promote patriotism, loyalty and service to others. The first chapter was formed in Fredericton, New Brunswick on January 15th 1900. Primary chapters were formed in quick succession across Canada. In 1901, Edith Boulton Nordheimer was elected the first national president, the location of the head office became Toronto, Ontario and the federation was incorporated as Imperial Order Daughters of the Empire and Children of the Empire Junior Branch. The Duke of Kent Chapter was formed in 1934 and was disbanded in 1980. During the 1970’s the name I.O.D.E. was officially adopted. It is a federally chartered not-for-profit, charitable organization. Structured to report under the jurisdiction of the National chapter are the Provincial chapters, the Municipal chapters and the Primary chapters. The I.O.D.E. is associated with the Victory League in England and Daughters of the British Empire in the United States and it is proud of its heritage and traditions. Queen Elizabeth II is the current patron of the organization and although chapters sometimes disband there are always new chapters forming, including e-chapters that meet through 21st century electronics.

Invitation: Gala Concert in honour of Her Majesty Queen Elizabeth and His Royal Highness the Duke of Edinburgh

An invitation from The Right Honourable Pierre Elliott Trudeau for a gala concert in the Opera of the National Arts Centre in honour of Her Majesty Queen Elizabeth and His Royal Highness the Duke of Edinburgh.

Richard III as duke of Gloucester and King of England

UANL