Rheumatology Commons^™

Transcriptional Inhibition Of Type I Collagen Gene Expression In Scleroderma Fibroblasts By The Antineoplastic Drug Ecteinascidin 743., Natalia Louneva, Biagio Saitta, David J Herrick, Sergio A. Jimenez

Department of Medicine Faculty Papers

We previously showed that COL1A1 expression is up-regulated at the transcriptional level in systemic sclerosis (SSc) fibroblasts and that the CCAAT-binding factor (CBF) is involved in this increased expression. Ecteinascidin 743 (ET-743) is a chemotherapeutic agent that binds with sequence specificity to the minor groove of DNA and inhibits CBF-mediated transcriptional activation of numerous genes. Therefore, we examined the effects of ET-743 on the increased COL1A1 expression in SSc fibroblasts. The drug caused a potent and dose-dependent inhibition of type I collagen biosynthesis, which reached 70-90% at 700 pM without affecting cell viability. The same drug concentration caused 60-80% reduction …

Are Antinuclear Antibodies And Rheumatiod Factor Positivity More Prevalent In Apparently Healthy Smokers Compared To Ex-Smokers And Never Smokers?, Susan Nyanzi

Loma Linda University Electronic Theses, Dissertations & Projects

Context: There is now consistent evidence from population and epidemiological studies that cigarette smoking is an independent risk factor for Rheumatoid Arthritis (RA), via Rheumatoid Factor (RF) production (Deighton, 1997; Saag, 1997; Silman, 1996; Uhlig, 1999; Wolfe, 2000). Antinuclear Antibodies (ANA) are another collection of autoantibodies that are being associated with smoking and RA initiation. To our knowledge, no studies have examined the effects of smoking on both ANA and RF simultaneously in healthy subjects.

Objectives: To determine whether cigarette smoking has an effect on ANA and RF positivity in healthy blood donors.

Design, Setting, Participants: This was a cross-sectional, …

Systemic Sclerosis: Current Views Of Its Pathogenesis., Chris T. Derk, Sergio A. Jimenez

Department of Medicine Faculty Papers

Systemic sclerosis (SSc) is an autoimmune disorder of unknown etiology characterized by severe and often progressive cutaneous and visceral fibrosis, pronounced alterations in the microvasculature, and numerous cellular and humoral immune abnormalities. Clinically, SSc is very heterogeneous, encompassing a spectrum ranging from mild limited forms of skin sclerosis with minimal internal organ involvement to severe skin and multiple internal organ fibrosis. Mortality and morbidity in SSc are very high and are directly related to the extent of the fibrotic and microvascular alterations. A better understanding of the pathogenesis of this incurable disorder will help to better target and design effective …

Regulation And Localization Of Endogenous Human Tristetraprolin, Anna-Marie Fairhurst, John E. Connolly, Katharine A Hintz, Nicolas J Goulding

Dartmouth Scholarship

Tumor necrosis factor (TNF) has been implicated in the development and pathogenicity of infectious diseases and autoimmune disorders, such as septic shock and arthritis. The zinc-finger protein tristetraprolin (TTP) has been identified as a major regulator of TNF biosynthesis. To define its intracellular location and examine its regulation of TNF, a quantitive intracellular staining assay specific for TTP was developed. We establish for the first time that in peripheral blood leukocytes, express

Regulation Of Human Col9a1 Gene Expression. Activation Of The Proximal Promoter Region By Sox9., Ping Zhang, Sergio A. Jimenez, David G Stokes

Department of Medicine Faculty Papers

The COL9A1 gene contains two promoter regions, one driving expression of a long alpha1(IX) chain in cartilage (upstream) and one driving expression of a shorter chain in the cornea and vitreous (downstream). To determine how the chondrocyte-specific expression of the COL9A1 gene is regulated, we have begun to characterize the upstream chondrocyte-specific promoter region of the human COL9A1 gene. Transient-transfection analyses performed in rat chondrosarcoma (RCS) cells, human chondrosarcoma (HTB) cells, and NIH/3T3 cells showed that the COL9A1 promoter was active in RCS cells but not HTB or NIH/3T3 cells. Inclusion of the first intron had no effect on promoter …

The Role Of Meat, Poultry, And Fish Consumption In The Occurrence Of Rheumatoid And Other Forms Of Arthritis, Asnake Hailu

Loma Linda University Electronic Theses, Dissertations & Projects

Rheumatoid arthritis and other forms of arthritis or rheumatism are now the leading cause of disability in the United States. The etiology and pathogenesis are less understood and available treatment options are not always satisfactory. This dissertation measures the prevalence and cumulative incidence of rheumatoid arthritis and other forms of arthritis or rheumatism, and examines any associations with current and lifetime consumption of meat, poultry, and fish (meat) using the Adventist Health Study and the Adventist Mortality Study databases. From these databases, it was possible to reconstruct a prospective cohort, obtain self-reported information on demographic characteristics, arthritis, rheumatoid arthritis, other …