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Mulibrey nanism (for muscle-liver-brain-eye nanism, MUL; MIM 253250) is an autosomal recessive disorder that involves several tissues of mesodermal origin, implying a defect in a highly pleiotropic gene. Characteristic features include severe growth failure of prenatal onset and constrictive pericardium with consequent hepatomegaly. In addition, muscle(More)
We developed methods for measuring inflammatory biomarkers (cytokines, chemokines, and metalloproteinases) in synovial biopsy specimens from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Soluble extracts of synovial fragments were prepared with mild detergent and analyzed by enzyme-linked immunosorbent assay (ELISA) for interleukin 1beta(More)
BACKGROUND Familial cold autoinflammatory syndrome (FCAS) is an autosomal dominant disorder characterised by recurrent episodes of rash, arthralgia, and fever after cold exposure. The genetic basis of this disease has been elucidated. Cryopyrin, the protein that is altered in FCAS, is one of the adaptor proteins that activate caspase 1, resulting in release(More)
The study of fibroblast-like synoviocytes (FLS) has yielded important insights into the pathogenic mechanisms of rheumatoid arthritis. FLS can be cultured from synovial tissue obtained at joint replacement surgery, synovectomy, or synovial biopsy. After collagenase digestion, adherent cells consist mainly of synovial fibroblasts and synovial macrophages.(More)
OBJECTIVE Treatment with the anti-CD20 monoclonal antibody (mAb) rituximab is effective in rheumatoid arthritis (RA). Marked depletion of circulating B cells, seen in almost all patients, does not correlate with efficacy. The potential synovial immunomodulatory effects of rituximab have not been fully defined. METHODS The ARISE trial is an open label,(More)
Neutrophil granulocytes, while migrating, undergo substantial shape changes from the round, resting state to a polarized phenotype. In the present study, we monitored cell volume changes in neutrophils migrating toward the chemotactic agent N-formyl-methionyl-leucyl-phenylalanine (FMLP) in collagen gels. Neutrophil volume was measured through optical(More)
Neutrophils increase volume (approximately 15%) when stimulated in suspension, but whether a similar alteration occurs in vivo during migration is unknown. We measured neutrophil volume using serial 0.5-micron sections and three-dimensional reconstruction of rabbit neutrophils migrating into inflammatory lesions in lung and abdominal wall in vivo and of(More)
The p53 tumor suppressor protein plays a central role in cell cycle regulation, DNA repair, and apoptosis. Recent studies indicate that DNA damage and somatic mutations in the p53 gene can occur because of genotoxic stress in many tissues, including the skin, colon, and synovium. Although somatic mutations in the p53 gene have been demonstrated in(More)
The neutrophil granulocyte is considered to play a key role in the inflammatory process, contributing to the increased microvascular permeability and tissue damage seen at inflammatory sites. The mechanism underlying this process is unknown, but studies in vitro using cultured endothelium and blood polymorphonuclear granulocytes (PMNs) point to an(More)
Insulin-like growth factor (IGF)-I increases muscle mass while myostatin inhibits its development. Muscle wasting is common in patients with uremic cachexia and may be due to imbalance of this regulation. We had proposed a central mechanism involving leptin and melanocortin signaling in the pathogenesis of uremic cachexia since agouti-related peptide(More)