Rheumatology Commons^™

Molecular Ablation Of Tgf-Beta Signaling Pathways By Tyrosine Kinase Inhibition: The Coming Of A Promising New Era In The Treatment Of Tissue Fibrosis, Joel Rosenbloom, Sergio A. Jimenez

Selected Works of Sergio Jiménez, MD, MACR

No abstract provided.

The Role Of Allograft Inflammatory Factor 1 In Systemic Sclerosis, Francesco Del Galdo, Carol M. Artlett, Sergio A. Jimenez

Selected Works of Sergio Jiménez, MD, MACR

ABSTRACT

Purpose: To review studies which support the hypothesis that allograft inflammatory factor-1 (AIF-1), a protein initially identified in chronically rejected cardiac allografts, may be involved in the pathogenesis of the progressive fibroproliferative vasculopathy which is a hallmark of systemic sclerosis (SSc).

Recent findings: Recent findings demonstrated elevated AIF-1 expression both in SSc affected tissues and peripheral blood mononuclear cells. A detailed immunohistopathologic study examined the tissue and cellular localization of the protein in affected SSc tissues and demonstrated its expression in the endothelium of dermal and pulmonary vessels, in the pulmonary parenchyma, and in relevant inflammatory cells including T …

Description Of Twelve Cases Of Nephrogenic Fibrosing Dermopathy And Review Of The Literature, Fabian A. Mendoza, Carol M. Artlett, Nora Sandorfi, Kevin Latinis, Sonoles Piera-Velazquez, Sergio A. Jimenez

Selected Works of Sergio Jiménez, MD, MACR

ABSTRACT

Objectives: To review the clinical and laboratory features of twelve cases of nephrogenic fibrosing dermopathy (NFD) studied at our institution and of 70 previously described cases in the literature.

Methods: Clinical evaluation and laboratory studies of twelve patients with NFD associated with chronic hemodialysis or peritoneal dialysis for end-stage renal disease and a review of 23 previous publications describing 70 patients with this disease.

Results: Eleven patients undergoing chronic hemodialysis and one patient undergoing chronic peritoneal dialysis for end-stage renal failure developed a severe and progressive cutaneous fibrotic process with woody induration of legs, thighs, hands and forearms, and …

Inhibition Of Collagen Gene Expression In Systemic Sclerosis Dermal Fibroblasts By Mithramycin, Nora Sandorfi, Natalia Louneva, Elena Hitraya, Gyorgy Hajnoczky, Biagio Saitta, Sergio A. Jimenez

Selected Works of Sergio Jiménez, MD, MACR

ABSTRACT

Introduction. The antitumor antibiotic mithramycin has also been shown to be a potent and effective inhibitor of fibrosis following glaucoma surgery. This DNA interacting drug displays high affinity binding to GC rich sequences in DNA, including those present in the promoter of the gene encoding the Α1 chain of type I collagen (COL1A1).

Objective. To evaluate the effects of mithramycin on the production of type I collagen in fibroblast cultures from patients with systemic sclerosis. Methods. Confluent cultures of dermal fibroblasts from patients with recent onset of the diffuse form of systemic sclerosis were treated with varius concentrations of …

B-Myb Acts As A Repressor Of Human Col1a1 Collagen Gene Expression By Interacting With Sp1 And Cbf Factors In Scleroderma Fibroblasts, Lucia Cicchillitti, Sergio A. Jimenez, Arturo Sala, Biaggio Saitta

Selected Works of Sergio Jiménez, MD, MACR

We investigated the role of B-Myb, a cell-cycle-regulated transcription factor, in the expression of the alpha1 (I) pro-collagen gene (COL1A1) in scleroderma fibroblasts. Scleroderma or SSc (systemic sclerosis) is a fibrotic disease characterized by excessive production of extracellular matrix components, especially type I collagen. Northern-blot analysis showed an inverse relationship between COL1A1 mRNA expression and that of B-Myb during exponential cell growth and during quiescence in human SSc fibroblasts. Overexpression of B-Myb in SSc fibroblasts was correlated with decreased COL1A1 mRNA expression. Transient transfections localized the down-regulatory effect of B-Myb to a region containing the proximal 174 bp of the …

Regulation Of Type-Ii Collagen Gene Expression During Human Chondrocyte De-Differentiation And Recovery Of Chondrocyte-Specific Phenotype In Culture Involves Sry-Type High-Mobility-Group Box (Sox) Transcription Factors, David G. Stokes, Gang Liu, Rita Dharmavaram, David Hawkins, Sonsoles Piera-Velazquez, Sergio A. Jimenez

Selected Works of Sergio Jiménez, MD, MACR

During ex vivo growth as monolayer cultures, chondrocytes proliferate and undergo a process of de-differentiation. This process involves a change in morphology and a change from expression of chondrocyte-specific genes to that of genes that are normally expressed in fibroblasts. Transfer of the monolayer chondrocyte culture to three-dimensional culture systems induces the cells to re-acquire a chondrocyte-specific phenotype and produce a cartilaginous-like tissue in vitro. We investigated mechanisms involved in the control of the de-differentiation and re-differentiation process in vitro. De-differentiated chondrocytes re-acquired their chondrocyte-specific phenotype when cultured on poly-(2-hydroxyethyl methacrylate) (polyHEMA) as assayed by morphology, reverse transcriptase PCR of …

Role Of Protein Kinase C-Delta In The Regulation Of Collagen Gene Expression In Scleroderma Fibroblasts, Sergio A. Jimenez, Svetlana Gaidarova, Biagio Saitta, Nora Sandorfi, David J. Herrich, Joan C. Rosenbloom, Umberto Kucich, William R. Abrams, Joel Rosenbloom

Selected Works of Sergio Jiménez, MD, MACR

Working with cultured dermal fibroblasts derived from control individuals and patients with systemic sclerosis (SSc), we have examined the effects of protein kinase C-delta (PKC-delta) on type I collagen biosynthesis and steady-state levels of COL1A1 and COL3A1 mRNAs. Rottlerin, a specific inhibitor of PKC-delta, exerted a powerful, dose-dependent inhibition of type I and type III collagen gene expression in normal and SSc cells. Optimal rottlerin concentrations caused a 70-90% inhibition of type I collagen production, a >80% reduction in COL1A1 mRNA, and a >70% reduction in COL3A1 mRNA in both cell types. In vitro nuclear transcription assays and transient transfections …

Identification Of Fetal Dna And Cells In Skin Lesions From Women With Systemic Sclerosis, Carol M. Artlett, J. Bruce Smith, Sergio A. Jimenez

Selected Works of Sergio Jiménez, MD, MACR

BACKGROUND: Systemic sclerosis is a disease of unknown origin which often occurs in women after their childbearing years. It has many clinical and histopathological similarities to chronic graft-versus-host disease. Recent studies indicate that fetal stem cells can survive in the maternal circulation for many years post partum. This finding suggests that fetal cells persisting in the maternal circulation or tissues could be involved in the pathogenesis of systemic sclerosis by initiating a graft-versus-host reaction.

METHODS: We used the polymerase chain reaction (PCR) to identify Y-chromosome sequences in DNA extracted from peripheral-blood cells and skin lesions from women with systemic sclerosis …

Stimulation Of Alpha 1(I) Procollagen Gene Expression In Nih-3t3 Cells By The Human T Cell Leukemia Virus Type 1 (Htlv-1) Tax Gene., E. Munoz, D. Suri, S. Amini, K. Khalili, Sergio A. Jimenez

Selected Works of Sergio Jiménez, MD, MACR

The mechanisms that regulate the expression of genes encoding extracellular matrix proteins in fibroblasts and other mesenchymal cells have remained elusive. Studies from several laboratories have indicated that Tax, a trans-regulatory protein from the human T cell leukemia virus type I not only augments viral gene expression but also triggers the expression of various cellular genes. Here, we examined the hypothesis that the expression of collagen genes may also be modulated by Tax. NIH-3T3 cells were simultaneously transfected with a Tax expressor plasmid and a chimeric construct containing regulatory sequences (-804 to +42 bp) of the alpha 1(I) procollagen gene …

The Tight Skin Mouse: Demonstration Of Mutant Fibrillin-1 Production And Assembly Into Abnormal Microfibrils, Cay M. Kielty, Michael Raghunath, Linda D. Siracusa, Michael J. Sherratt, Reiner Peters, C. Adrian Shuttleworth, Sergio A. Jimenez

Selected Works of Sergio Jiménez, MD, MACR

Mice carrying the Tight skin (Tsk) mutation harbor a genomic duplication within the fibrillin-1 (Fbn 1) gene that results in a larger than normal in-frame Fbn 1 transcript. In this study, the consequences of the Tsk mutation for fibrillin-containing microfibrils have been examined. Dermal fibroblasts from Tsk/+ mice synthesized and secreted both normal fibrillin (approximately 330 kD) and the mutant oversized Tsk fibrillin-1 (approximately 450 kD) in comparable amounts, and Tsk fibrillin-1 was stably incorporated into cell layers. Immunohistochemical and ultrastructural analyses of normal and Tsk/+ mouse skin highlighted differences in the gross organization and distribution of microfibrillar arrays. Rotary …