Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An epitope common for collagen type II and Clq was demonstrated by specific binding of a monoclonal anti-collagen type II antibody, MAb B1, to purified Clq. This was further substantiated by the affinity shown between F(ab')2 fragments of anti-Clq antibodies and rat chondrosarcoma collagen type II. The interaction between MAb B1 and Clq was demonstrated in hemolytic assays, in an enzyme-linked biotin-avidin assay and by the binding of Clq to MAb B1 immobilized on Sepharose 4B beads. MAb B1 recognized only purified Clq and not the macromolecular Cl complex, indicating that the epitope for MAb B1 was situated in the collagen-like region in Clq, where Clq and Cls are anchored. The binding of the purified collagen-like fragment of Clq to radiolabelled MAb B1 confirmed these findings. The affinity between MAb B1 and Clq was significantly increased if Clq was first reacted with heat aggregated IgG, indicating a demasking of the reactive epitope on binding to the aggregated IgG. The present findings raise the question of the pathogenetic significance of the presence of anti-collagen type II antibodies and free Clq, both of which are frequently seen in high amounts in rheumatoid arthritis.
Mol Immunol 1989 Feb
PMID:Common epitopes in Clq and collagen type II. 246 89

Binding of C3 to sheep erythrocytes in a serum-free milieu (EAC14oxy2, EAC142) has previously been shown to mimic the antigenic change that occurs upon denaturation of C3 in sodium dodecyl sulphate (SDS), whereby neoantigenic C3(D) epitopes are exposed. The present paper deals with C3 bound to various target surfaces which are known to modulate the functional properties of C3 in different ways. Bound C3 fragments on serum-treated human aggregated gammaglobulin, zymosan, rabbit and sheep erythrocytes, and on circulating immune complexes isolated from sera of patients with rheumatoid arthritis and systemic lupus erythematosus, were shown to be mainly in the iC3b form. By RIAs, employing polyclonal antibodies, the range of C3(D) antigenic epitopes of 125I-labelled SDS denatured C3 expressed by the particle-bound iC3b was monitored. The physiologically bound iC3b on all tested particles expressed wide range of C3(D) epitopes and each type of particle-bound C3 exposed its individual range. By competition ELISA specific C3(D) alpha epitopes were monitored, employing monoclonal antibodies. A distinct difference in the expression of these epitopes was observed in iC3b bound to various test particles in the presence of normal serum and in iC3b present on circulating immune complexes from pathological sera. Considering that the neoantigenic C3(D) epitopes have been shown to be associated with different functions of C3, the distinctive antigenic expression of each type of serum-treated particle might reflect different functional forms of the protein.
Mol Immunol 1989 Apr
PMID:Distinctive expression of neoantigenic C3(D) epitopes on bound C3 following activation and binding to different target surfaces in normal and pathological human sera. 246 49

An immunoglobulin G (IgG) preparation of the serum from a patient with active Graves' disease was used to isolate cDNA clones from a lambda gt11 cDNA library of human thyroid follicular carcinoma tissue by immunoscreening. One of these clones, hML-7, is further characterized herein by sequencing, Northern analysis, and chromosomal mapping. The clone reacted with IgG preparations from the sera of 14 of 19 patients with active Graves' disease but not with IgG preparations from 11 normal individuals, three patients with toxic thyroid adenoma, and three with rheumatoid arthritis. The hML-7 cDNA hybridized to a 3.6 kilobase (kb) mRNA transcript in poly(A+) RNA preparations from human thyroid tissue and continuously cultured rat thyroid cells; expression of this transcript in rat FRTL-5 thyroid cells was positively regulated by TSH. The 3.6 kb transcript was less abundant in rat liver (BRL3A) cells or differentiated rat (L6) myoblasts than in cultured rat thyroid cells and was not detectable in mouse L-M fibroblasts, human IM-9 lymphocytes, Chinese hamster ovary cells, or human cervical carcinoma cells. The cDNA from hML-7 was sequenced and compared with the sequence of cross-hybridizing cDNA clones isolated from human Graves' thyroid and rat FRTL-5 thyroid cell lambda gt11 expression libraries. A 1.05 kb open reading frame, which is highly conserved between human and rat, was defined. The predicted amino acid sequence of 348 residues exhibited a strong homology with the mitochondrial ADP/ATP carrier protein (adenine nucleotide translocase; ADP/ATP translocator) and with two other members of the same mitochondrial protein family, the phosphate carrier and the hydrogen ion uncoupling protein. The gene represented by the hML-7 cDNA has been assigned to human chromosome 10.
Mol Endocrinol 1989 Sep
PMID:Sequence and chromosomal assignment of a novel cDNA identified by immunoscreening of a thyroid expression library: similarity to a family of mitochondrial solute carrier proteins. 257 20

T suppressor cells differentiate from bone marrow precursors when cocultured with thymic epithelium, a thymic-derived cytokine TsIF, or mixture of both. (TsIF is a trademark of Ventrex Laboratories, Inc., Portland, ME, and is the subject of a U.S. patent by Ventrex Laboratories, Inc., Portland, ME.) These cells, when transplanted into the lupus-rheumatoid arthritis-prone mouse, prevent acquisition of disease as assessed by lack of both antinuclear antibody, rheumatoid factor, and survival beyond mean time for MRL/lpr mice. When TsIF is administered directly into these lupus-rheumatoid arthritis-prone mice, an equivalent sparing effect is manifested.
Mol Biother 1989
PMID:Action of a thymic cytokine TsIF in reversing the autoimmune disease state of the MRL/1pr mouse. 268 25

Long-term synovial fibroblast cultures were exposed to interleukin 1 (IL-1) or prostaglandin E2 (PGE2). The normally spindle-shaped fibroblasts changed to stellate-shaped cells, resembling the HLA-DR-positive, collagenase-producing cells which are normally seen only in primary cultures from enzyme-digested rheumatoid synovial tissue. However, the IL-1- or PGE2-induced fibroblasts were not HLA-DR-positive. This suggests that these cell populations represent originally different cell lines or that the expression of HLA-DR antigens is not induced by the agents used. For further characterization of these stellate cells, the location of fibronectin and type I collagen was studied by specific antibodies and the pericellular coat around fibroblasts was visualized by the erythrocyte exclusion method. Both IL-1 and PGE2 treatments destroyed the intercellular fibronectin network. Type I collagen was detected as intracellular granules. The stellate fibroblasts were usually full of these granules in contrast to intact fibroblasts in which the number of collagen fluorescence granules varied greatly. The pericellular coat known to be formed mainly by hyaluronic acid was similar around spindle and stellate-shaped fibroblasts. Rheumatoid arthritis-derived fibroblasts did not differ from their non-rheumatoid counterparts in any of the experiments. The effect of IL-1 and PGE2 on fibroblasts simulates the interaction between mononuclear cells and fibroblasts in synovial stroma and also potentially the interactions between different cell types in synovial lining.
Virchows Arch B Cell Pathol Incl Mol Pathol 1986
PMID:Connective tissue components in synovial fibroblast cultures exposed to interleukin 1 and prostaglandin E2. 287 May 82

The ability of enzyme-dissociated synovial adherent cells (SAC) obtained from patients with active rheumatoid arthritis to restore the proliferation and differention of peripheral blood mononuclear non-adherent cells (NAC) into immunoglobulin-secreting cells (ISC) was investigated. Autologous combinations of cells were used in this study to eliminate allogeneic reactions. Peripheral blood NAC, prepared by glass adherence and leucine methylester treatment to remove monocytes, almost completely lost their capacity to proliferate and differentiate into ISC in response to pokeweed mitogen. The response of NAC was restored by adding 12.5% of 'fresh SAC', which was obtained by glass-adherence after an overnight culture of non-rosette forming, enzyme-dissociated rheumatoid synovial cells. Although the response was also restorable by adding more than 25% fresh SAC, this was less satisfactory than adding 12.5% SAC. 'Old SAC', obtained by glass-adherence after 7 days culture of enzyme-dissociated synovial cells, did not restore the response of NAC. Immunohistochemical studies showed that 55% of fresh SAC and 3% of old SAC expressed HLA-DR antigens. When 100 units/ml of interferon gamma was present, 25% of old SAC remained HLA-DR-positive and some of these cells retained a dendritic morphology after 7 days culture. The results indicate that rheumatoid synovia contain macrophage-like cells that can effectively support the ultimate differentiation of lymphocytes to ISC.
Virchows Arch B Cell Pathol Incl Mol Pathol 1988
PMID:The restoration of proliferation and differentiation of peripheral blood mononuclear non-adherent cells into immunoglobulin-secreting cells by autologous synovial adherent cells from patients with rheumatoid arthritis. 289 43

The clinical trials performed with bovine superoxide dismutase (SOD) are reviewed. SOD, applied intraarticularly at a dosage of 2-16 mg, proved to be effective in osteoarthritis of the knee joint in three placebo-controlled and one steroid-controlled double-blind trials. Its efficacy in other inflammatory joint disorders is documented by uncontrolled trials. Similarly, some controlled and many open studies support the efficacy of locally injected SOD in periarticular inflammation. Systemic treatment of rheumatoid arthritis by SOD at the dosages indicated yielded disappointing results. Well documented, though open uncontrolled studies demonstrated beneficial effects of locally administered SOD in radiation cystitis, interstitial cystitis and Peyronie's disease. Tolerance is good, but allergic reactions at low incidence have to be anticipated. Human SOD derived from recombinant microorganisms is being developed to explore its therapeutic potential particularly in ischemia-reperfusion damage, adult respiratory distress or similar conditions.
Mol Cell Biochem 1988 Dec
PMID:Superoxide dismutase for therapeutic use: clinical experience, dead ends and hopes. 306 19

Auranofin (AF) is an orally active chrysotherapeutic agent used for the treatment of rheumatoid arthritis, a self-perpetuating inflammatory disease. Because of reports suggesting that AF and other gold complexes can, under certain circumstances, exacerbate rheumatoid inflammatory lesions in humans and adjuvant arthritic rats and that phospholipase C (PLC) and phospholipase A2 activities are increased in rheumatoid patients, the effects of AF and a related gold complex on in situ mammalian and purified Bacillus cereus PLC were examined. Results of our studies show that 1) AF and triethylphosphine gold chloride (TEPG), an AF analog, stimulated PLC activity in the sonicate of RAW 264.7 macrophages; 2) AF and TEPG stimulated B. cereus PLC activity in a concentration-dependent manner, but the pattern of stimulation and concentrations of drugs required to stimulate the purified enzyme differ from those seen with the macrophage PLC; 3) metals (cobalt and zinc) and sulfhydryl reagents (N-ethylmaleimide, iodoacetic acid, and glutathione), tested at the same concentrations of AF that enhanced PLC activity, had no effect on the enzyme. These data suggest that stimulation of PLC may be a generic phenomenon since two divergent PLCs are affected by gold complexes. Additionally, these studies may provide one potential explanation for rheumatoid lesion flares seen in patients and animals on chrysotherapy.
Mol Pharmacol 1987 Sep
PMID:Effect of auranofin and other gold complexes on the activity of phospholipase C. 311 79

Cartilage degradation is a characteristic feature of various types of human arthritis, notably rheumatoid arthritis and osteoarthritis. The influence of glucocorticoid and other steroid hormones on cartilage proteoglycan breakdown was examined in a model system in which breakdown is readily quantified by the release of proteoglycan from cultured bovine nasal cartilage discs. Endotoxin (bacterial lipopolysaccharides) treatment enhanced the depletion of cartilage proteoglycan by 2-3 fold. This was inhibited in a concentration-dependent manner by hydrocortisone (10(-9) to 10(-5) M) or other glucocorticoid hormones (dexamethasone, prednisolone, cortisone). Inhibition required the continued presence of the steroid. Removal of hydrocortisone (3 x 10(-7) M) after 4 days from endotoxin-treated cultures resulted in the rapid restoration of an endotoxin response, so that proteoglycan release approached maximum levels during a second 4-day culture period. Other C-21 steroid hormones (progesterone, aldosterone) were also inhibitory at 10(-5) M, but testosterone and beta-estradiol showed little influence on endotoxin action. Proteoglycan products of smaller average mol wt (Sepharose CL-2B chromatography), consistent with core protein cleavages, were released from endotoxin-treated cartilage. Cleavage was unaffected by beta-estradiol, partially blocked by aldosterone and largely prevented by hydrocortisone administration.
Mol Cell Biochem 1988 Jan
PMID:Effect of steroid hormones on endotoxin-mediated cartilage degradation. 337 77

Metallothioneins (MTs) are low molecular weight, thiol-rich, metal-binding proteins. Auranofin (AF) is a gold compound active in the treatment of rheumatoid arthritis. The effects of AF on regulation of MT gene expression in Chinese hamster ovary cells were studied. AF-resistant cells accumulated substantial amounts of MT mRNA and protein, whereas no induction was observed in AF-sensitive cells. Cells capable of inducing MT in the presence of AF were much less sensitive to AF-mediated cytotoxicity. Induction of MT by low concentrations of Cd protected cells from subsequently administered doses of AF. The level of protection correlated with the level of induced MT. These findings indicate that MT plays a central role in the mechanisms underlying cellular resistance to gold compounds.
Mol Pharmacol 1987 Jan
PMID:Induction of metallothionein is correlated with resistance to auranofin, a gold compound, in Chinese hamster ovary cells. 380 90


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>