Dupuytren's contracture (DC), a benign disease of unknown origin, is characterized by abnormal fibroblast proliferation and matrix deposition within the palmar and plantar faciae, causing contracture of the digits. Conventional cytogenetic studies of cultured fibroblast cells from DC nodules have revealed nonrecurrent, but usually normal, clonal (mainly +7, +8, and -Y, plus structural changes) and sporadic (nonclonal) numerical/structural rearrangements. No unique cytogenetic features of DC are known so far. We used 44K oligonucleotide-based array comparative genomic hybridization to obtain a wide pattern of chromosomal imbalances in 18 patients with DC. The genome-wide analysis revealed no changes of DNA copy number sequences. Accordingly, gene amplifications or deletions are apparently not involved in the progression of abnormal fibroblast proliferation and matrix deposition that lead to DC.
"We take the approach of comparing primary fibroblasts derived from surgically resected DD contracture (cord) tissue (DD cells) to fibroblasts derived from the palmar fascia of the adjacent, phenotypically unaffected digit exposed during surgery (PF cells). While DD may be associated with increased cancer mortality in some populations  , patients with a family history of finger contractures do not display any major chromosomal rearrangements or deletions  and DD is considered a benign, heritable fibrosis . Single nucleotide polymorphisms (SNPs) have been identified as potential markers of this heritability , and these polymorphisms are predicted to be present in all somatic tissues in these patients rather than limited to Biochimica et Biophysica Acta 1832 (2013) 1511–1519 ☆ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. "
[Show abstract][Hide abstract] ABSTRACT: Dupuytren's Disease (DD) is a common and heritable fibrosis of the palmar fascia that typically manifests as permanent finger contractures. The molecular interactions that induce the development of hyper-contractile fibroblasts, or myofibroblasts, in DD are poorly understood. We have identified IGF2 and IGFBP6, encoding insulin-like growth factor (IGF)-II and IGF binding protein (IGFBP)-6 respectively, as reciprocally dysregulated genes and proteins in primary cells derived from contracture tissues (DD cells). Recombinant IGFBP-6 inhibited the proliferation of DD cells, patient-matched controls (PF) cells and normal palmar fascia (CT) cells. Co-treatments with IGF-II, a high affinity IGFBP-6 ligand, were unable to rescue these effects. A non-IGF-II binding analog of IGFBP-6 also inhibited cellular proliferation, implicating IGF-II-independent roles for IGFBP-6 in this process. IGF-II enhanced the proliferation of CT cells, but not DD or PF cells, and significantly enhanced DD and PF cell contractility in stressed collagen lattices. While IGFBP-6 treatment did not affect cellular contractility, it abrogated the IGF-II-induced contractility of DD and PF cells in stressed collagen lattices. IGF-II also significantly increased the contraction of DD cells in relaxed lattices, however this effect was not evident in relaxed collagen lattices containing PF cells. The disparate effects of IGF-II on DD and PF cells in relaxed and stressed contraction models suggest that IGF-II can enhance lattice contractility through more than one mechanism. This is the first report to implicate IGFBP-6 as a suppressor of cellular proliferation and IGF-II as an inducer of cellular contractility in this connective tissue disease.
[Show abstract][Hide abstract] ABSTRACT: This paper describes the results of tests to determine the effects
of brake-beam guide-slot lines and empty/load devices on wheel sliding.
Wheel slides cause wheel spalling. The results of the tests indicate
that empty/load devices with improved response characteristics that
provide a lower braking ratio significantly reduce the incidence of
wheel slides. Further, testing showed some improvement between the
sliding behavior of axles equipped with new design types of polymer
brake-beam guide-slot lines
Railroad Conference, 1999. Proceedings of the 1999 ASME/IEEE Joint; 02/1999
[Show abstract][Hide abstract] ABSTRACT: The trap generation in oxides between 5 nm and 13.5 nm thick has
been measured as a function of the oxide electric field, oxide
thickness, stress time, and electron fluence during constant voltage
stresses. It was found that the trap generation could be accurately
described by an Eyring equation of the form
<sup>0.2</sup> for all thicknesses of oxides and all stresses. This
Eyring formulation for the trap generation supports the electric field
model (E-model) of oxide breakdown. The activation energy obtained for
trap generation predicts a different activation energy for breakdown
very close to that found in long-time, low-field breakdown measurements
Physical and Failure Analysis of Integrated Circuits, 1999. Proceedings of the 1999 7th International Symposium on the; 02/1999
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.