Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human polymorphonuclear neutrophil (PMN) granule extract (25 mug of protein) released 60 percent of the available 35SO4 from labeled rabbit articular cartilage in 0.5 hour at neutral pH. N-acetyl-L-alanyl-L-alanyl-L-prolyl-L-alanine choloromethyl ketone (NAcAAPACK), a specific elastase inhibitor, was only minimally effective against whole granule extract, and N-alpha-tosyl-L-lysine chloromethyl ketone, which inhibits trypsin but not elastase, was completely ineffective. Preparative disc-gel electrophoresis of PMN granule extract revealed two separate regions with independent activity against 35SO4-labeled cartilage. One region contained elastases and when tested alone, was completely inhibited by NAcAAPACK. The other contained lysozyme and two esterases active against N-acetyl-L-phenylalanine-alpha-naphthol. Purified lysozyme proved inactive, suggesting that the chymotrypsin-like esterases were responsible for proteoglycan degradation by this region of the gel.
Arthritis Rheum
PMID:Identification of neutral proteases in human neutrophil granules that degrade articular cartilage proteoglycan. 23 25

Lewis rats developed polyarthritis after a single injection of a water-in-oil emulsion containing various peptidoglycans (PGs) derived from Lactobacillus plantarum. A copolymer of polyriboinosinic acid and polyribocytidylic acid markedly potentiated the arthritogenicity of these PGs. The synthetic adjuvants N-acetylmuramyl-L-alanyl-D-isoglutamine (MurNAc-L-Ala-D-isoGln) and MurNAc-L-Ala-D-Gln were non-arthritogenic, but they did produce severe arthritis when mixed in a water-in-oil emulsion with a copolymer of polyriboinosinic acid and polyribocytidylic acid. Substitution of either L-isoGln or D-isoAsn for the D-isoGln in the MurNAc-L-Ala-D-isoGln markedly reduced its capacity to induce the disease. Taken together with the results of skin testing against various PGs and MurNAc-L-Ala-D-isoGln in the diseased rats, the present results suggest that (i) a minimal essential structure required for development of polyarthritis is related to a larger molecule than either MurNAc-L-Ala-D-isoGln or a monomer of PG, probably to a dimer of PG, and (ii) an antigenic determinant(s) for the delayed-type skin hypersensitivity to PGs exists on a common structure shared among these PGs, possibly somewhere on a monomer of PG not on N-acetylmuramyl peptides.
 ...
PMID:Synergistic effect of polyriboinosinic acid:polyribocytidylic acid and either bacterial peptidoglycans or synthetic N-acetylmuramyl peptides on production of adjuvant-induced arthritis in rats. 54 92

Peptidyl fluoromethyl ketones (FMKs), with the amino acid sequence Phe-Ala held constant but with variable N-terminal groups, were synthesized and tested for inhibition of the cysteine proteinase cathepsin B. The FMKs were effective in inhibiting cathepsin B activity in vitro. The inhibition was time dependent and was not reversed by dialysis, suggesting covalent modification of the enzyme. Cathepsin B activity present in livers and kidneys of rats treated with FMKs was reduced by 22-91% 4 hr after a single oral dose of 25 mg/kg. The FMKs inhibited the severity of inflammation and the extent of cartilage and bone damage in adjuvant-induced arthritis. These effects were seen during the late-stage of the disease with no effect on onset or incidence of disease. This is consistent with inhibition of protease-mediated damage. These FMKs or derivatives may be of clinical value in the treatment of arthritis.
 ...
PMID:Peptidyl fluoromethyl ketones as inhibitors of cathepsin B. Implication for treatment of rheumatoid arthritis. 141 42

Prior studies have shown that patients with rheumatoid arthritis (RA) have an increased number of circulating Epstein-Barr virus-infected B lymphocytes and elevated titers of antibody to Epstein-Barr nuclear antigen-1 (EBNA-1), the major nuclear antigen expressed in latently infected B cells. However, it is not known whether antibodies from RA patients recognize the same epitopes as antibodies from normal subjects. are directed at the glycine-alanine repeating region of the molecule. Antibodies specific for this region are also somewhat more prevalent in RA patients than in normal subjects. A panel of synthetic peptides derived from EBNA-1 was used to analyze the immune response to antigenic epitopes outside the glycine-alanine region, using the peptides as solid-phase antigen. Sera from RA patients and from systemic lupus erythematosus patients contained elevated levels of IgG antibodies to 2 non-glycine-alanine peptide and to 3 non-glycine-alanine peptides, respectively. Two of the 3 peptides are glycine-rich, but antibodies that react with them are distinct from each other, as well as from those that react with the glycine-alanine epitope. Eight other peptides from the C-terminal portion of EBNA-1 either do not react with sera or show no difference between normal subjects and patient groups. The antibodies to the glycine-alanine peptide are enriched with kappa light chains, whereas antibodies to epitopes outside the glycine-alanine region are not so restricted among kappa and lambda light chains. Thus, RA patients and systemic lupus erythematosus patients have different antibody responses than do normal subjects, both quantitatively and qualitatively.
Arthritis Rheum 1990 Jul
PMID:Altered immune response to glycine-rich sequences of Epstein-Barr nuclear antigen-1 in patients with rheumatoid arthritis and systemic lupus erythematosus. 216

Lyme disease was first recognized in 1975 because of a cluster of patients with arthritis in the vicinity of Lyme, Connecticut. Subsequently the arthritis was linked with erythema chronicum migrans (88%), cardiac (8%), and nervous system diseases (11%). By 1983, the etiology of the disease had been confirmed as an infection caused by a spirochete, Borrelia burgdorferi, transmitted to man by the bite of a tick, Ixodes dammini. Then it became apparent that this was the same disease reported as far back as the 1920's, known in Europe as tick-borne meningeal polyneuritis, lymphocytic meningoradiculitis, or Bannwarth's syndrome. The usual presentation includes exposure to ticks or tick-infested areas of the Northeast, the characteristic rash, and then the neurological abnormalities, then the arthritis. This case is presented to illustrate the possible presence of the disease with no history of tick exposure, no travel to areas usually considered endemic and no characteristic rash.
Ala Med 1990 Jan
PMID:Possible Lyme meningitis. 231 38

The DR1 and DRw10 beta 1 chain genes were isolated from each of 2 individuals with rheumatoid arthritis who were heterozygous for these class II major histocompatibility complex specificities. The sequences of the DR1 beta 1 chains from both patients were identical, differing from previously reported DR beta 1 chains of individuals without RA by 2 amino acid substitutions, at positions 85 (Val-Ala) and 86 (Gly-Val), and by a silent mutation at the last nucleotide of codon 78 (C-T), resulting in the loss of a Pst I restriction endonuclease site. Identical DRw10 beta 1 chain genes were found in both patients. These were shown to encode the epitope recognized by monoclonal antibody 109d6. This antibody also recognizes an epitope on the DRw53 beta 2 chain of the DR4 haplotype. The third diversity regions of the DR1 beta (amino acids 67-74) and the DRw10 beta 1 chains (amino acids 67-73) were identical, respectively, with those of the DR4 (Dw14) beta 1 and beta 2 chains, raising the possibility that in these patients, the third diversity regions of the two DR beta 1 chain genes present in trans are conformationally equivalent to the cis-encoded third diversity regions of the DR4 (Dw14), DR beta 1, and beta 2 chains. The nucleotide sequences of the DQ beta complementary DNA clones were identical to that of the DQw1 beta chain, and no DR beta 2 complementary DNA clones were identified.
Arthritis Rheum 1989 Mar
PMID:Class II major histocompatibility complex gene sequences in rheumatoid arthritis. The third diversity regions of both DR beta 1 genes in two DR1, DRw10-positive individuals specify the same inferred amino acid sequence as the DR beta 1 and DR beta 2 genes of a DR4 (Dw14) haplotype. 293 Jun

The role of cathepsin B, H and L activities in arthritic processes was studied histochemically using specific synthetic substrates in a postcoupling method on unfixed and undecalcified cryostat sections of rat knee joints. Only cathepsin B in synoviocytes, chondrocytes and fibroblasts showed a strong increase in activity due to antigen induced arthritis. The addition of a tissue stabilizer, polyvinyl alcohol, to the incubation medium enabled us to demonstrate extracellular enzymic activity within the articular cartilage matrix of arthritic joints. Both intravenous and oral treatment of the animals with a selective inhibitor of cathepsin B, Z-Phe-Ala fluoromethyl ketone (CH2F), during the development of arthritis suppressed the degree of inflammation and resulted in decreased intracellular and extracellular cathepsin B activity as detected histochemically, and less cartilage damage. Our study indicates that (a) cathepsin B-like activity plays a role in the cascade of proteolytic cartilage destruction, (b) chondrocytes and fibroblasts may well be involved in the breakdown of cartilage and ligaments, and (c) Z-Phe-AlaCH2F could be of therapeutic value.
 ...
PMID:Cysteine proteinase activity in arthritic rat knee joints and the effects of a selective systemic inhibitor, Z-Phe-AlaCH2F. 320 99

The mechanism of transport of alanine and aminoisobutyric acid into chondrocytes in rabbit articular cartilage was shown to be mediated by transport systems similar to that described for other eukaryotic cells namely the A, ASC, and L systems. Three days after the initiation of an acute inflammatory arthritis by the intra-articular injection of carrageenin into one knee joint the rate of transport of both these amino acids was decreased. Although all three transport systems were depressed, it appeared that the A and ASC systems were partially susceptible to damage by the induced inflammation. The rate of amino acid transport by the affected cartilage had recovered by 28 days after carrageenin treatment. This depression in amino acid transport is discussed in relation to a decrease in general metabolic processes in chondrocytes as a consequence of inflammation.
 ...
PMID:Carrageenin-induced arthritis. VI. Alterations in amino acid transport by articular cartilage in acute inflammatory arthritis. 402 8

A series of N-(2-benzoylphenyl)alanine derivatives were synthesized and tested for antiinflammatory activity in the Evans blue-carrageenan induced pleural effusion assay. The target compounds were envisioned to bind to a receptor site on the cyclooxygenase enzyme by a mechanism first proposed by Appleton and Brown. Of the 21 compounds prepared, two were found to be one-tenth as potent as indomethacin in the pleurisy model and one compound was tested and found to be weakly active in the adjuvant arthritis model.
 ...
PMID:Antiinflammatory activity of N-(2-benzoylphenyl)alanine derivatives. 648 68

Peptidoglycan (PG)-polysaccharide (PS) polymers derived from group A streptococcal cell walls were solubilized by M-1 mutanolysin (endo-N-acetylmuramidase) and phage-associated lysin (N-acetylmuramyl-l-alanine amidase). Fragments were isolated by ultrafiltration and a series of gel filtrations and were injected intravenously into Sprague-Dawley rats. No fragments with a molecular weight of less than 5 x 10(6) were able to induce arthritis by systemic injection. However, the enzyme-derived fragments displayed a new biological activity. High-molecular-weight PG-PS fragments ( congruent with500,000) derived from mutanolysin digests induced a severe edematous reaction in the front and hind limbs. The response started 5 to 10 min postinjection, reached maximum intensity in approximately 30 min, and disappeared by 10 h. The smallest dose capable of eliciting the response was 0.31 mug/g of body weight. Low-molecular-weight PG-PS ( congruent with30,000) derived from the mutanolysin digests and the PG-PS fragments isolated from phage-associated lysin digests also induced edema; however, a higher dose was required to elicit the same response as that produced by high-molecular-weight PG-PS fragments. The active fragments contained rhamnose, glucosamine, muramic acid, alanine, glutamic acid, and lysine in various molar ratios. PG-PS fragments obtained by sonic degradation of cell walls (molecular weight >/=5.3 x 10(6)), as well as enzyme-treated PG preparations and muramyl dipeptide, failed to elicit the response. These findings indicate that PG-PS fragments of sizes too small to be arthritogenic can affect the vascular endothelium to induce a rapidly developing edema. Fragments with this biological property could have a key role in the pathogenesis of experimental arthritis by influencing the tissue distribution of arthritogenic PG-PS.
 ...
PMID:Soluble peptidoglycan-polysaccharide fragments of the bacterial cell wall induce acute inflammation. 675 2


1 2 3 4 5 6 7 8 Next >>