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)

The growth of new blood vessels plays an important role in the pathogenesis of several diseases including cancer, diabetes, and arthritis. Beta-cyclodextrin tetradecasulfate, when administered with an appropriate steroid inhibits angiogenesis, and can stimulate angiogenesis when given alone. The regulation of angiogenesis is not well understood, and the mechanism of action of beta-cyclodextrin tetradecasulfate is similarly not well defined. Ecto-protein kinase activity that utilizes extracellular ATP has recently been reported on several types of cells. Human neutrophils appear to possess two distinct ecto-protein kinase activities; one that phosphorylates exogenous substrates including vitronectin and basic fibroblast growth factor, and one that phosphorylates endogenous cell-surface proteins. This report shows that beta-cyclodextrin tetradecasulfate inhibits the phosphorylation of the exogenous substrates casein, vitronectin (the major ecto-protein kinase substrate in serum), and basic fibroblast growth factor by human neutrophil ecto-protein kinase activity. In contrast, beta-cyclodextrin tetradecasulfate had no effect on the phosphorylation of endogenous cell-surface proteins by the neutrophil ecto-protein kinase activity. Ecto-protein kinase activity that was inhibited by beta-cyclodextrin tetradecasulfate was also detected on porcine aortic and human umbilical vein endothelial cells. The effects of beta-cyclodextrin tetradecasulfate on ecto-protein kinase activities may play a role in its effects on angiogenesis.
 ...
PMID:The angiogenesis inhibitor beta-cyclodextrin tetradecasulfate inhibits ecto-protein kinase activity. 128 48

Articular cartilage from arthritic joints of rats immunized with type II collagen is severely depleted of proteoglycans. Depletion begins within 48 hours after the onset of inflammation, prior to extensive pannus formation, and may represent a critical first step in cartilage destruction. We have immunolocalized stromelysin, an enzyme that is believed to play a major role in the pathologic degradation of proteoglycans, in the joints of rats with collagen-induced arthritis. Immunoperoxidase staining of frozen tissue sections demonstrated the presence of stromelysin in both the synovium and chondrocytes. In contrast, collagenase was localized primarily to the pannus-cartilage junction. Neither enzyme was detectable in joints from normal animals. To test the hypothesis that chondrocytes respond directly to inflammatory mediators by increasing the production of stromelysin, isolated chrondrocytes were incubated with various concentrations of interleukin-1. The culture media were also assayed for the presence of stromelysin by immunoreactivity on Western blots and by analysis of enzymatic activity on casein substrate gels. A 3-fold increase in a doublet of proteins synthesized in response to 10 units/ml of interleukin-1 was observed. These proteins also immunoreacted with the stromelysin antibody and degraded casein. Northern blotting results established that the increased levels of stromelysin were accompanied by increases in stromelysin-specific messenger RNA levels. These results suggest that stromelysin is responsible for proteoglycan degradation in early inflammatory arthritis, and that chondrocytes may play a direct role in the earliest stages of the degradation of their own matrices.
Arthritis Rheum 1990 Mar
PMID:The role of stromelysin in the cartilage destruction that accompanies inflammatory arthritis. 215 11

Functional and morphological changes of the gastrointestinal system were assessed in patients suffering from juvenile chronic arthritis, juvenile systemic erythematosus and juvenile systemic scleroderma. The results of endoscopic investigation of the gastrointestinal tract showed inflammatory changes and cardiac and pylorus atony. Ultrasonography results suggested hepatic and pancreatic inflammatory changes, steatosis and/or amyloidosis. The above-mentioned changes were confirmed by morphological investigation (biopsy and/or autopsy). The results of the capacity tests performed in JCA (systemic form) patients revealed an impairment of liver detoxication function, and pancreas and bowel functional capacity as well. Additionally, intolerance against lactose, casein and alpha- and beta-lactoglobulin was found in most of the patients. Some symptoms of malnutrition were observed in all of them. Such factors as underlying disease severity, adverse drug effects, environmental factors (infections, nutrition) were taken into consideration as probable causes of the gastrointestinal system damage.
 ...
PMID:[Changes in the gastrointestinal system of children with inflammatory systemic connective tissue diseases]. 865 92

The effect of oral bacteriotherapy with human Lactobacillus casei strain GG (10(10) colony-forming units twice daily for 10 days) was investigated in Crohn's disease and in juvenile chronic arthritis which are chronic inflammatory diseases associated with impaired mucosal barrier function. During oral bacteriotherapy, the gut immune response was indirectly assessed by solid-phase enzyme-linked immunoassay in 14 children with Crohn's disease, in 9 with juvenile chronic arthritis, and in 7 controls. The immunostimulatory effect of Lactobacillus GG was specific for Crohn's disease, irrespective of its activity: the mean (95% confidence interval) number of specific antibody secreting cells in the IgA class to beta-lactoglobulin increased significantly from 0.2 (0.04-1.3) to 1.4 (0.3-6.0)/10(6) cells and to casein from 0.3 (0.1-1.4) to 1.0 (0.2-4.8)/10(6) cells. The results indicate that orally administered Lactobacillus GG has the potential to increase the gut IgA immune response and thereby to promote the gut immunological barrier. Consequently, Lactobacillus GG could provide an adjunct nutritional therapy for Crohn's disease.
 ...
PMID:Promotion of IgA immune response in patients with Crohn's disease by oral bacteriotherapy with Lactobacillus GG. 886 96

ADAM 12 is a member of a family of disintegrin-containing metalloproteases that have been implicated in a variety of diseases including Alzheimer's disease, arthritis, and cancer. We purified ADAM 12 from the urine of breast cancer patients via Q-Sepharose anion exchange and gelatin-Sepharose affinity chromatography followed by protein identification by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Four peptides were identified that spanned the amino acid sequence of ADAM 12. Immunoblot analysis using ADAM 12-specific antibodies detected an approximately 68-kDa band identified as the mature form of ADAM 12. To characterize catalytic properties of ADAM 12, full-length ADAM 12-S was expressed in COS-7 cells and purified. Substrate specificity studies demonstrated that ADAM 12-S degrades gelatin, type IV collagen, and fibronectin but not type I collagen or casein. Gelatinase activity of ADAM 12 was completely abrogated by zinc chelators 1,10-phenanthroline and EDTA and was partially inhibited by the hydroxamate inhibitor Marimastat. Endogenous matrix metalloprotease inhibitor TIMP-3 inhibited activity. To validate our initial identification of this enzyme in human urine, 117 urine samples from breast cancer patients and controls were analyzed by immunoblot. The majority of samples from cancer patients were positive for ADAM 12 (67 of 71, sensitivity 0.94) compared with urine from controls in which ADAM 12 was detected with significantly lower frequency. Densitometric analyses of immunoblots demonstrated that ADAM 12 protein levels were higher in urine from breast cancer patients than in control urine. In addition, median levels of ADAM 12 in urine significantly increased with disease progression. These data demonstrate for the first time that ADAM 12 is a gelatinase, that it can be detected in breast cancer patient urine, and that increased urinary levels of this protein correlate with breast cancer progression. They further support the possibility that detection of urinary ADAM 12 may prove useful in the development of noninvasive diagnostic and prognostic tests for breast and perhaps other cancers.
 ...
PMID:ADAM 12 cleaves extracellular matrix proteins and correlates with cancer status and stage. 1538 92

Data implicate IL-1 in the altered matrix biology that characterizes human intervertebral disc (IVD) degeneration. In the current study we investigated the enzymic mechanism by which IL-1 induces matrix degradation in degeneration of the human IVD, and whether the IL-1 inhibitor IL-1 receptor antagonist (IL-1Ra) will inhibit degradation. A combination of in situ zymography (ISZ) and immunohistochemistry was used to examine the effects of IL-1 and IL-1Ra on matrix degradation and metal-dependent protease (MDP) expression in explants of non-degenerate and degenerate human IVDs. ISZ employed three substrates (gelatin, collagen, casein) and different challenges (IL-1beta, IL-1Ra and enzyme inhibitors). Immunohistochemistry was undertaken for MDPs. In addition, IL-1Ra was introduced into degenerate IVD explants using genetically engineered constructs. The novel findings from this study are: IL-1Ra delivered directly onto explants of degenerate IVDs eliminates matrix degradation as assessed by multi-substrate ISZ; there is a direct relationship between matrix degradation assessed by ISZ and MDP expression defined by immunohistochemistry; single injections of IVD cells engineered to over-express IL-1Ra significantly inhibit MDP expression for two weeks. Our findings show that IL-1 is a key cytokine driving matrix degradation in the degenerate IVD. Furthermore, IL-1Ra delivered directly or by gene therapy inhibits IVD matrix degradation. IL-1Ra could be used therapeutically to inhibit degeneration of the IVD.
Arthritis Res Ther 2007
PMID:Interleukin-1 receptor antagonist delivered directly and by gene therapy inhibits matrix degradation in the intact degenerate human intervertebral disc: an in situ zymographic and gene therapy study. 1776 Sep 68

We evaluated the effects of a casein hydrolysate (CH) prepared from Aspergillus oryzae protease on rat adjuvant arthritis, a model of human rheumatoid arthritis. CH was administered orally once a day to the animals for 22 d after the adjuvant injection. CH suppressed swelling in the adjuvant-uninjected hind paws, and a higher dose of CH suppressed the increase in arthritic score and swelling of the adjuvant-injected hind paws. A histopathological examination revealed evidence that the higher dose of CH suppressed the articular changes in the rats. In addition, CH suppressed the production of nitric oxide and prostaglandin E(2) in the plasma of the rats. These results suggest that CH had a suppressive effect on adjuvant arthritis by inhibiting the acute and chronic inflammatory reactions.
 ...
PMID:Effects of a casein hydrolysate prepared from Aspergillus oryzae protease on adjuvant arthritis in rats. 1868 19

Arthritis is one of the most prevalent chronic inflammatory diseases, and it is characterized by structural and biochemical changes in major tissues of the joint, including degradation of the cartilage matrix, insufficient synthesis of extracellular matrix (ECM). Ecklonia cava (EC) is a member of the family of Laminariaceae, which is an edible marine brown alga with various bioactivities. In this study of the methanol extract of brown alga EC, the dieckol (1) and 1-(3',5'-dihydroxyphenoxy)-7-(2'',4'',6''-trihydroxyphenoxy) 2,4,9-trihydroxydibenzo-1,4,-dioxin (2) were isolated and characterized by NMR techniques with high yield. Phlorotannin derivatives (1, 2) promoted osteosarcoma differentiation by increasing alkaline phosphatase (ALP) activity, mineralization, total protein and collagen synthesis in human osteosarcoma cell (MG-63 cells), respectively. Furthermore, these phlorotannin derivatives (1, 2) inhibited mRNA gene and protein levels of matrix metalloproteinase (MMP-1, MMP-3, and MMP-13), iNOS and COX-2 in casein zymography, Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR) assays. In addition, it was observed that the phlorotannins inhibited phosphorylation of JNK and p38 MAPK in human osteosarcoma cell. These results suggested the phlorotannin derivatives (1, 2) could promote cell differentiation, attenuate MMP-1, MMP-3, MMP-13 expressions, and inflammatory response via MAPK pathway in chronic articular diseases.
 ...
PMID:Differentiation of human osteosarcoma cells by isolated phlorotannins is subtly linked to COX-2, iNOS, MMPs, and MAPK signaling: implication for chronic articular disease. 1933 Aug 80

Enzyme-linked immunosorbent assays (ELISA) have been widely used to determine quantitatively autoantibodies. However, the processes for the purification and immobilization of antigens in conventional ELISA methods include multiple steps, which have hampered the application for screening of autoantibodies. Here, we have developed a novel ELISA system using the plates pre-coated with glutathione casein to capture recombinant proteins fused to N-terminal glutathione S-transferase (GST). The GST-fused proteins were synthesized with the wheat germ cell-free protein production system. Thus, the present system combined the GST-capture ELISA with the cell-free protein production system, which allowed immobilization of the recombinant proteins with one-step purification. Using this ELISA method, we determined whether rheumatoid factors (RF), which have been considered as one of the representative disease-specific autoantibodies for rheumatoid arthritis (RA), were genetically associated with severity of arthritis in a mouse model for RA, MRL/Mp-lpr/lpr (MRL/lpr). GST-fused human IgG1-Fc (GST-Fc), synthesized with the robotic protein synthesizer, were used as reactants for RF. Serum samples for RF were prepared from 11 lines of a recombinant inbred mouse strain, MXH/lpr, which was established from intercrosses between MRL/lpr and non-arthritic C3H/HeJ-lpr/lpr (C3H/lpr) strains, composed of a different genomic recombination derived from the parental strains in each line. A correlation of RF titers with the severity of the arthritis in these lines was not significant, indicating genetic dissociation of RF from arthritis and that RF is not necessarily required for the development of RA. The present method may provide high-throughput screening for determining the disease-specific autoantibodies in autoimmune diseases.
 ...
PMID:Evaluating the role of rheumatoid factors for the development of rheumatoid arthritis in a mouse model with a newly established ELISA system. 2020 15

Matrix metalloproteinases (MMPs), also known as matrixins, belong to a group of zinc-dependent proteins, which are thought to play a central role in the breakdown of extracellular matrix. Collagen, elastin, gelatin and casein are major components cleaved by MMPs. The breakdown of these components is essential for many physiological processes such as embryonic development, morphogenesis, reproduction, and tissue resorption and remodelling. MMPs also participate in pathological processes such as arthritis, cancer, cardiovascular and neurological diseases. This review summarizes current knowledge regarding these proteins, their participation in physiological and pathophysiological roles, their involvement in activation and inhibition, and their interactions with other metal-binding proteins including metallothioneins.
 ...
PMID:Matrix metalloproteinases. 2084 7


1 2 Next >>