ABSTRACT
Diffuse-type tenosynovial giant cell tumors, also known as pigmented villonodular synovitis, are unique mesenchymal lesions that arise from the synovial tissue of the joints. They are predominantly intraarticular, aggressive, infiltrative processes, characterized by both inflammatory or neoplastic properties and local destructive progression. The pattern of synovial gene and protein expressions in pigmented villonodular synovitis, similar to those in activated macrophages in rheumatoid arthritis, and the phenotype of multinucleated giant cells, characteristic of osteoclasts, suggest that there is a common autocrine mechanism in osteoclast differentiation in both diseases and indicate the potential utility of tumor necrosis factor (TNF)-alpha blockade. High synovial colony stimulating factor 1 (CSF1) messenger RNA (m RNA) expression in pigmented villonodular synovitis, unrelated to a chromosomal translocation involving CSF1 locus, may indicate that there is a synergic paracrine loop mediated by TNF-alpha and CSF1, as shown in both inflammatory and neoplastic conditions. The effects of a new therapeutic approach consisting in intraarticular TNF-alpha blockade were studied in four pigmented villonodular synovitis knees. Knee injections produced a rapid reduction in clinical and sonographic indexes and immunohistological alterations, confirmed by arthroscopic synovectomy. A delayed relapse in one of the four knees and unaltered synovial CSF1 expression were other important findings. In the light of these observations, CSF1/CSF1R interaction probably represents a more sensible therapeutic target than TNF-alpha blockade in the diffuse form of pigmented villonodular synovitis.
Subject(s)
Knee Joint , Macrophage Colony-Stimulating Factor/metabolism , Synovial Membrane/immunology , Synovial Membrane/pathology , Synovitis, Pigmented Villonodular/immunology , Synovitis, Pigmented Villonodular/metabolism , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adult , Arthritis/drug therapy , Arthritis/immunology , Arthritis/metabolism , Arthritis/pathology , Connective Tissue Cells , Female , Gene Expression , Giant Cell Tumors/immunology , Giant Cell Tumors/pathology , Giant Cells/metabolism , Giant Cells/pathology , Humans , Knee Joint/pathology , Macrophage Colony-Stimulating Factor/biosynthesis , Macrophage Colony-Stimulating Factor/genetics , Male , Middle Aged , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Signal Transduction , Synovial Fluid/metabolism , Synovitis, Pigmented Villonodular/drug therapy , Synovitis, Pigmented Villonodular/pathologyABSTRACT
The enzyme kynurenine aminotransferase (KAT) catalyses the conversion of L-kynurenine to kynurenic acid. A combination of polymerase chain reaction techniques and hybridization screening was used to isolate a cDNA clone encompassing the entire coding region of KAT from rat kidney. Identification of the cDNA as coding for KAT was based both on the comparison of amino acid sequences obtained from purified rat KAT and on the expression of KAT activity in COS-1 cells transfected with the cDNA. RNA blot analysis indicated that KAT mRNA is widely expressed in rat tissues. Cultured cells transfected with the cDNA for KAT also showed glutamine transaminase K activity. Based mainly on sequence data, these results demonstrate that rat kidney KAT is identical with glutamine transaminase K.
Subject(s)
Lyases , Transaminases/genetics , Amino Acid Sequence , Animals , Base Sequence , Cell Line , Cloning, Molecular , DNA, Complementary , Kidney/enzymology , Molecular Sequence Data , RatsABSTRACT
Eight outpatients with sickle cell disease received six EMG and six thermal half-hour biofeedback training sessions. Statistically significant changes in the desired directions were obtained for the following variables: (a) frontalis muscle tension, (b) digital temperature, (c) frequency of headache as a crisis symptom, (d) frequency of analgesic use, (e) perceived pain intensity, (f) frequency of self-treated crises, and (g) state anxiety. Nonsignificant changes in hospital chart data were found. A 6-month posttreatment follow-up questionnaire revealed the continued effectiveness of the training received regarding headaches and mild pains.