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

1. Normal synovial membrane contains approximately equal proportions of two genetically distinct forms of collagen, types I and III. The proportion of these two collagens is unchanged in rheumatoid synovium but in addition a small amount of basement membrane collagen is present. Tissue culture of rheumatoid synovium confirms the synthesis of both type I and III collagens. 2. In young normal synovium both type I and type III collagens are stabilized by a reducible keto cross-link, which is replaced in adult tissue by an as yet unknown non-reducible cross-link. During the proliferation of the collagen in adult rheumatoid synovium a high proportion of the keto cross-link is present. This cross-link is not susceptible to cleavage by D-penicillamine, nor does the drug have any effect on the rate of synthesis in vitro. The mode of action of D-penicillamine in rheumatoid arthritis does not appear to involve a direct effect on the synovial membrane collagen.
Clin Sci Mol Med 1978 Jul
PMID:Changes in the collagen of synovial membrane in rheumatoid arthritis and effect of D-penicillamine. 35 1

1. Foetal rat hemi-calvaria were incubated in organ culture with sera from patients with active rheumatoid arthritis. 2. Increased 45Ca resorption was produced by sera from patients who were hypercalcaemic. 3. This bone-resorbing effect could be inhibited by calcitonin.
Clin Sci Mol Med 1976 Aug
PMID:Bone-resorbing activity in the sera of patients with rheumatoid arthritis. 95 67

A mammalian autoantigen of the nucleolus organizing regions (NORs) was identified by a human autoantibody from the serum of a rheumatoid arthritis patient. The distribution and changes of NORs during the cell cycle of mammals were followed by using this autoantiserum in indirect-immunofluorescence microscopy. In interphase cells the staining pattern indicated that the autoantigen is restricted exclusively within the nucleolus. This fluorescence appeared punctuated rather than uniform, and it was reorganized during inhibition of transcription in cells treated with actinomycin D. During mitosis, the autoantigen was detected by light microscopy at the chromosomal nucleolus organizer regions, indicating that presumably the protein remains bound to the rRNA genes. Biochemical analysis by immunoblotting showed that the NOR autoantigen consists of two polypeptides with molecular masses apparent of 90-92 kDa in all of the mammalian cell lines tested. The identity of some epitopes, recognized by this autoantibody as the ribosomal transcription factor UBF, is discussed.
Cell Mol Biol (Noisy-le-grand) 1992 Dec
PMID:Immunostaining of nucleolus organizers in mammalian cells by a human autoantibody against the polymerase I transcription factor UBF. 128 27

Organoid or high density cultures of: (1) synovial cells from patients with rheumatoid arthritis, and (2) prechondrogenic mesenchymal cells from limb buds of 12-day-old mouse embryos, were co-cultured for 7-10 days using the Trowell culture system. Depending on the time of commencing co-cultivation, chondrogenesis was inhibited (co-cultivation from the start) or the cartilaginous matrix was partly degraded (co-cultivation after formation of embryonic cartilage, i.e. on day 4). These effects were obtained with cells from synovial fluid as well as from synovial tissue. Matrix degradation and the behaviour of the different cell types could be demonstrated well by electron microscopy under the in vitro conditions applied.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:Influence of synovial cells on cartilage in vitro: induction of breakdown and inhibition of synthesis. 135 95

RHP has been purified from the plasma of both normal individuals and patients with rheumatoid arthritis (RA). RHP from both these sources was shown to be identical with Factor H by reaction with antisera and N-terminal amino acid sequence analysis. Factor H, from both normal and RA sera, inhibited the solubilization of immune precipitates but did not affect prevention of immune precipitation. Factor H was shown to inhibit the haemolytic activity of fluid-phase C1, but unlike C1-inhibitor, it had little effect on C1 bound to EA (EAC1). Factor H was shown to complex with intact C1, to isolated C1q and to the C1r:C1s tetramer. However, binding of factor H to C1 did not dissociate the C1 macromolecule. A C1-Factor H complex was detected in the serum and plasma from normal individuals and patients with systemic lupus erythematosus and RA. Serum levels of this complex were reduced, by EDTA-treatment of serum and by activation of complement by the classical pathway.
Mol Immunol
PMID:Purification and characterization of RHP (factor H) and study of its interactions with the first component of complement. 138 42

Cryoimmunoglobulins are associated with numerous clinical problems ranging from collagen vascular disorders (rheumatoid arthritis and systemic lupus erythematosus) to infectious processes including HIV infection. The precise role of cryoglobulins in the pathophysiology of these disorders remains unresolved. Although cold insolubility may account for some of the observed processes, it cannot explain the entire array of findings in cryoglobulinemia. An alternative hypothesis suggests that the subtle differences responsible for cold precipitation of these proteins renders them intrinsically more sticky, resulting in deposition of cryoimmunoglobulins on vascular surfaces. We have explored this hypothesis by characterizing the binding of monoclonal cold soluble and cryoimmunoglobulins to silica beads as a model biological surface. It is found that monoclonal, type I, IgM and IgG cryoglobulins have only a slight tendency to bind to a greater extent to this surface than cold soluble immunoglobulins. Physical studies utilizing front surface fluorescence measurements and differential scanning calorimetry show surface interaction leads to partial thermal destabilization of the proteins. To a limited extent, this destabilization is more pronounced with the cryoglobulins compared to cold-soluble control homologues. Surface bound IgM cryoimmunoglobulin was also found to fix complement less efficiently than their cold soluble surface bound counterparts. These studies do not strongly support the hypothesis that pathological mechanisms of cryoimmunoglobulins primarily involve abnormal surface interactions, although surface effects could play a limited role in some situations.
Mol Immunol 1991 Sep
PMID:The interaction of cryoimmunoglobulins with a model surface. 165 45

The principal existence of natural catalytic antibodies in the autoimmune sera is discussed. In the course of the autoimmune process, the induction of antiidiotypic antibodies against topoisomerase I has been shown in the sera of patients with scleroderma, systemic lupus erythematosus, and rheumatoid arthritis. The above antibodies were obtained in preparative amounts. Proceeding from the concept of the idiotypic network, the antibodies were suggested to be natural enzymes and their properties were studied. They appeared to be anti-DNA antibodies, competing with the native topoisomerase I for binding to anti-topoisomerase monoclonal antibodies and possessing highly specific DNA-binding activity (Kd is about 0.1 nM). The antiidiotypic antibodies specifically inhibit the topoisomerase-catalysed relaxation reaction and affect the formation of covalent DNA-protein complex. Possible involvement of antiidiotypic antibodies against topoisomerase in the catalysis of reactions of DNA transformation is analysed. Catalytic antibodies that are natural enzymes possessing DNA-nicking activity have been isolated from the blood sera of patients with different autoimmune pathologies.
Mol Biol (Mosk)
PMID:[Anti-idiotypic and natural catalytically active antibodies]. 165 16

Rheumatoid factors (RFs) are autoantibodies directed against IgG molecules. They are present in increased quantity in most patients with rheumatoid arthritis (RA), and are implicated in tissue damage in this disease. Paradoxically, recent studies of RFs have revealed that these autoantibodies are likely a physiological component of the immune system, and may play a role in the development and function of the B cell repertoire. Previously, we found that a significant fraction of RA patients express RF bearing the 6B6.6 cross-reactive idiotype, which is a phenotypic marker of the Humkv328-like genes. In order to elucidate the possible genetic factors that may contribute to the abnormal production of RFs in RA patients, we studied restriction fragment length polymorphisms (RFLP) of four highly homologous RF-related kappa light chain variable region (Vk) genes (i.e. Humkv328, Humkv328h2, Humkv328h5 and Humkv329) in RA patients and normal controls. The results show that kv328, kv328h2 and kv329 are likely to be alleles of the kv328 locus, while kv328h5 is a highly homologous Vk gene residing in a separate locus; and that deletion in one copy of either the kv328 or the kv328h5 loci, but not both loci, occurs in several individuals. However, the frequencies of various RFLP patterns of these two Vk gene loci are similar in patients and normals.
Mol Immunol 1991 Oct
PMID:Genetic studies of four highly homologous rheumatoid factor-associated Vk genes in rheumatoid arthritis patients and normal individuals. 168 28

Secreted human IL-1 beta is known to have two free SH groups due to unpaired cysteines (positions 8 and 71). Alpha 2-Macroglobulin (alpha 2-M) has internal thioester bonds between cysteine and glutamate residues. Free SH groups may be generated at these alpha 2M residues through the action of proteinases, amines such as methylamine, or at a slow rate, by H2O ("aging" of alpha 2M). Thus, the possibility that IL-1 beta forms a disulfide bond with alpha 2M was investigated. 125I-labeled human rIL-1 beta (15 kDa) was incubated with fresh normal human serum or with purified alpha 2M, treated or not with methylamine. The mixtures were submitted to nondenaturing and denaturing polyacrylamide gel electrophoresis (PAGE) followed by autoradiography. IL-1 beta bound to commercially purified "aged" alpha 2M and to alpha 2M in methylamine-treated serum but not to native serum alpha 2M. It did not bind detectably to any other serum proteins. The addition of D-penicillamine (D-pen) during the reaction of [125I]rIL-1 beta with serum or purified alpha 2M blocked the covalent binding of rIL-1 beta to alpha 2M. [125I]rIL-1 beta was removed from alpha 2M by 2-mercaptoethanol in SDS. Thus, disulfide bonds were formed between the free SH groups on [125I]rIL-1 beta and those resulting from the cleavage of the internal thioester bonds of alpha 2M. "Cold" rIL-1 beta and a Cys71----Ser71 rIL-1 beta mutant effectively competed with [125I]rIL.1 beta for binding sites on alpha 2M. When complexes of rIL-1 beta or the mutant rIL-1 beta and alpha 2M were subjected to nonreducing SDS-PAGE and subsequent Western blot analysis, the rIL-1 beta molecules were found to be present in the alpha 2M bands in a dose-dependent manner. rIL-1 beta attached to alpha 2M in the presence or absence of D-pen showed similar biological activity in the mouse thymocyte-assay. Thus, rIL-1 beta attached noncovalently to alpha 2M is biologically active. The lack of inhibition of rIL-1 beta activity by binding to methylamine-treated alpha 2M in the absence of D-pen suggests, but does not prove, that the covalently bound rIL-1 beta is also active. We concluded that human rIL-1 beta binds to alpha 2M through the Cys at position 8 and that D-pen inhibits this binding. We speculate that this inhibitory effect may contribute to the therapeutic benefits of D-pen in patients with rheumatoid arthritis.
Mol Immunol
PMID:Covalent disulfide binding of human IL-1 beta to alpha 2-macroglobulin: inhibition by D-penicillamine. 171 69

Class II HLA molecules are the most useful markers for susceptibility to different autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM) and rheumatoid arthritis (RA). Polymerase chain reaction and hybridization with a set of allele-specific oligonucleotide have been used for analysis of allelic sequence variation. The analysis of frequencies of HLA-DQA1 alleles among 10 patients of the russian population revealed a uneven distribution. We have developed a method for preparing non-radioactive oligonucleotide probes with terminal deoxynucleotidyl transferase and Bio-11-dUTP. Comparison of biotinylated and 32P-labeled hybridization probes gave the same sensitivity for HLA-DQA1 typing of amplified DNA. Amplification of the HLA-DQA1 gene has been successful on 10 pg of total DNA. This amount of DNA is close to the amount of DNA in a single cell. Alternatively, HLA-DQA1 typing could be based on the analysis of buccal cells of saliva that would avoid the problem of individuals who object to giving blood samples.
Mol Biol (Mosk)
PMID:[Use of the polymerase chain reaction for typing allelic variants of the human HLA-DQA1 by hybridization with oligonucleotide probes, specific for specific alleles]. 175 55


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