Reversal of TGF-β1 stimulation of α-smooth muscle actin and extracellular matrix components by cyclic AMP in Dupuytren's - derived fibroblasts

<p>Abstract</p> <p>Background</p> <p>Myofibroblasts, a derived subset of fibroblasts especially important in scar formation and wound contraction, have been found at elevated levels in affected Dupuytren's tissues. Transformation of fibroblasts to myofibroblasts is characterized by expression of alpha- smooth muscle actin (α-SMA) and increased production of extracellular matrix (ECM) components, both events of relevance to connective tissue remodeling. We propose that increasing the activation of the cyclic AMP (cAMP)/protein kinase A signaling pathway will inhibit transforming growth factor-beta1 (TGF-β₁)-induced ECM synthesis and myofibroblast formation and may provide a means to blunt fibrosis.</p> <p>Methods</p> <p>Fibroblasts derived from areas of Dupuytren's contracture cord (DC), from adjacent and phenotypically normal palmar fascia (PF), and from palmar fascia from patients undergoing carpal tunnel release (CTR; CT) were treated with TGF-β₁(2 ng/ml) and/or forskolin (10 μM) (a known stimulator of cAMP). Total RNA and protein extracted was subjected to real time RT-PCR and Western blot analysis.</p> <p>Results</p> <p>The basal mRNA expression levels of fibronectin- extra domain A (FN1-EDA), type I (COL1A2) and type III collagen (COL3A1), and connective tissue growth factor (CTGF) were all significantly increased in DC- and in PF-derived cells compared to CT-derived fibroblasts. The TGF-β₁stimulation of α-SMA, CTGF, COL1A2 and COL3A1 was greatly inhibited by concomitant treatment with forskolin, especially in DC-derived cells. In contrast, TGF-β₁stimulation of FN1-EDA showed similar levels of reduction with the addition of forskolin in all three cell types.</p> <p>Conclusion</p> <p>In sum, increasing cAMP levels show potential to inhibit the formation of myofibroblasts and accumulation of ECM components. Molecular agents that increase cAMP may therefore prove useful in mitigating DC progression or recurrence.</p

The composition of the manuscript of Christine de Pizan's Collected Works in the British Library: a reassessment

THE exquisite manuscript copy of Christine de Pizan's Collected Works, one of the greatest treasures of the British Library (Harley MS. 4431), is well known to scholars of late medieval literature and art. A splendid frontispiece depicts the first owner, Queen Isabeau of Bavaria, the wife of King Charles VI of France. Seated in the intimacy of her bedroom, Isabeau receives the large book from Christine, who wrote mostly for those prominent in royal circles between 1399 and 1416. A special dedication to the Queen precedes twenty-nine separate works by Christine, which together constitute the fullest version of her writings up to 1410-15, the date of its completion. Now bound in two volumes and containing 398 folios of large format, the British Library manuscript marks the culmination of Christine's literary career, which effectively began in 1389 when her husband, a royal secretary, died while on a mission for the King. Beset by financial difficulties, she became a writer in order to support herself and her family. By 1399, following ten years of study, the still-young widow had produced her first work, the Cent balades with which the Harley manuscript opens

The emergence of the Spanish illuminated haggadah manuscript.

In late thirteenth-century Spain, the Hebrew Passover haggadah appeared for the first time as an independent and decorated book. The purpose of this investigation is to develop an explanation for its emergence through the recovery of an original reading of the manuscripts and their decoration, insofar as this is possible. By shedding light on the function and meaning of this new type of book for its medieval readers, this project inserts the manuscripts (and their reading) within the historical narrative of Jewish grandeur and decline in fourteenth-century Christian Spain.The illuminated haggadah tradition demonstrates how Spanish Jews effectively expressed a cultural identity based on shifting relations of both resemblance to and difference from the majority Christian culture. In particular, the decoration reveals ways in which Jews continued to identify with the majority culture while finding creative ways to express their dissent or to subvert dominant ideologies. Each of the three most prominent aspects of the haggadah's artistic program illuminates this process of identity-formation by lending support to and actually expanding upon the ideological message already implicit in the text.First, the corpus of text illustrations is viewed in light of the rabbinic emphasis on teaching and learning. The rabbis sought to associate Jewish education with the survival of the Jews in terms of the power of tradition to act as a bulwark against hostile forces. The various types of illustration all draw upon the importance of tradition in asserting an unequivocal Jewish strength in the face of a more uncertain reality. Next, the striking image of the unleavened bread in each manuscript is viewed within the context of a contemporary visual discourse of power. When activated by the reading of the haggadah, this illustration effectively neutralized the threat to Jews posed by a number of Christian power-signs. Finally, the biblical miniature cycles included within ten of the manuscripts are understood in terms of the court Jews' stake in biblical narrative and national-religious historiography. They therefore bring narrative traditions and strategies to bear on the production of meaning and the construction of identity.Thesis (Ph.D.)--Northwestern University, 2000.School code: 0163

[catalog] Traces : people and the book /

Includes bibliographical references (p. 114-115)