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

Five patients who presented with arthritis as the sole manifestation of hereditary hemochromatosis and 51 family members were studied. Studies included clinical evaluation for the presence of arthritis and hemochromatosis, roentgenography of hands, knees, and pelvis, serum iron and serum ferritin measurements, complete HLA typing for 50 of the A and B loci, and, when indicated, liver biopsy. Arthritis occurred in 45 percent of persons with hemochromatosis. Although typical involvement of second and third metacarpophalangeal joints was observed in all five patients and some family members, two with typical arthritis did not have characteristic radiographic changes, two had constitutional symptoms without arthropathy, and one had unilateral hand changes. A specific HLA haplotype (A2/B17 in Family 1 and A29/B15 in Family 2) correlated with hereditary hemochromatosis but not with the arthropathy. Phlebotomy alleviated the early constitutional symptoms but did not help advanced arthritis. Anti-inflammatory drugs, intraarticular injections of glucocorticoids, and resection osteotomies of metacarpal heads were other treatment modalities.
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PMID:Arthritis of hemochromatosis. Clinical spectrum, relation to histocompatibility antigens, and effectiveness of early phlebotomy. 665 May 51

The results of a double-blind prospective study on patients with uncomplicated psoriasis (Ps), psoriasis with arthritis (PA) and a control group (C) are reported. The three groups were matched for age and sex. In the Ps and C groups no significant difference of the radiographic and scintigraphic results was found. The PA group showed significantly more scintigraphic accumulations compared to the two other groups, but no connection between scintigraphy and joint symptoms was found. The patients in the Ps and PA groups were treated with zinc sulfate per os for 8 weeks with no change in the radiographic findings. The PA group showed less and the Ps group more scintigraphic lesions after treatment. During treatment a small but significant decrease in hemoglobin, serum iron and gamma globulin was shown.
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PMID:Joint involvement in psoriasis: scintigraphic, radiologic and clinical findings. 687 18

Iron was readily demonstrated in chondrocytes in 3 of 4 hemochromatosis articular cartilages studied. Either apatite, calcium pyrophosphate dihydrate crystals, or both were found in all cartilages including those of 3 patients who had no radiographic or light microscopic evidence of calcification. These crystals, which may be secondary to degenerative changes or may play a role in cartilage degeneration, were not seen in any consistent morphologic relationship with the iron deposits. In fact, apatite was found in one cartilage in which no iron was identified in the sections studied. If iron, as demonstrated in the chondrocytes, is contributing to the calcium crystal deposition, it would most likely do so indirectly, for example by altering chondrocyte enzymes or connective tissue components.
Arthritis Rheum 1982 Dec
PMID:Articular cartilage in the degenerative arthropathy of hemochromatosis. 715 Mar 78

A 33-year-old white female of English descent with beta thalassaemia trait developed painful recurring bilateral knee effusion at age 15 years. Trauma was denied. Synovial analyses revealed noninflammatory effusions with normal complement, no inclusions, and no crystals. Knee x-rays normal at ages 18 and 26, showed mild osteoarthritic changes at age 33. Laboratory tests for other known causes of arthritis were repeatedly normal or negative. Bone densitometry was below normal. Light microscopy of the synovial membrane showed no significant abnormalities and no iron deposition. Electron microscopic findings included multilamination of vascular basement membranes and large amounts of thin fibrils surrounding many connective tissue cells. Treatment with salicylates did not prevent recurrence of effusions, and quadriceps strengthening and joint rest were moderately successful in relieving pain. Intra-articular corticosteroids on 2 occasions were not helpful. Whether her knee arthritis is purely secondary to the para-articular bone thinning from the chronic marrow expansion remains to be determined.
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PMID:Arthritis in beta thalassaemia trait: clinical and pathological features. 722 91

Siderosis of rabbit articular chondrocytes was produced in vitro as a model for the cartilage damage of hemophilic arthropathy. Both FeSO4 0.1-2.5 mM and rabbit hemoglobin (as hemolyzed serum, 14 mg/ml) caused iron storage in cell and organ culture. FeSO4 was far more effective. The fine structure of the siderosomes resulting from both iron sources was comparable to that observed in hemophilic and other forms of hemosiderosis. Particles resembling ferric oxyhydroxide were included in the FeSO4 but not the hemoglobin derived siderin. Iron storage following FeSO4 was enhanced 5-fold by culturing with rabbit rather than fetal calf serum. Despite repeated washing of the cultures and detachment with trypsin, an extracellular pool of Fe3+ persisted in the cell pellets. Cytotoxicity of Fe was manifested by formation of myelin bodies and a dose-dependent reduction of cell number. There was an inverse relationship between cytotoxicity and iron storage following administration of FeSO4 to five other cell types. Ascorbate 40 micrograms/ml stimulated DNA synthesis but had no protective effect against the cytotoxicity of FeSO4. Little erythrophagocytosis was showen by the chondrocytes. Desferrioxamine (0.01--2.5 mM) was markedly toxic for dividing but not for stationary chondrocytes. Administered after iron storage had been induced with FeSO4, 1.0--2.5 mM desferrioxamine removed stainable siderin granules over the course of 4 days.
Arthritis Rheum 1981 Jun
PMID:Experimental siderosis of articular chondrocytes cultured in vitro. 724 76

The natural history of arthritis associated with idiopathic haemochromatosis was studied in 18 male patients over a 10 year period. Chondracalcinosis was present radiologically in at least on joint in seven patients initially and developed later in 13, with the articular cartilages of the wrists and knees affected most frequently. During the period of observation seven patients developed chondrocalcinosis in the wrists, seven in the knees, three in the hips, one in the symphysis pubis and two in the spine. In no patient did the chondrocalcinosis decrease or disappear. The development and progression of chondrocalcinosis was not affected by treatment of iron overload by venesection. The presence of chondrocalcinosis in at least one joint was not related to the age of the patient at the initial or follow-up examination or to the amount of iron removed by venesection (p greater than 0.05, Wilcoxon rank sum test). Arthritis (loss of joint space, cysts, destruction of articular surfaces) usually with associated symptoms and signs affected the hands in eight patients initially and developed later in 13. Arthritis of large joints was uncommon and none of the patients in the present series developed destructive arthritis of hips or knees. This contrast with the finding in a retrospective survey of 93 patients with idiopathic haemochromatosis seen since 1967 at King's College Hospital in which seven patients had destructive arthritis affecting the hips.
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PMID:The natural history of arthritis in idiopathic haemochromatosis: progression of the clinical and radiological features over ten years. 733 Jan 69

We identify a function-controlling O antigen chain length for a plasmid-borne gene, cldpHS-2, harboured by Flexneri strains of Escherichia coli known to cause reactive arthritis. The predicted amino acid sequence of the gene product is very similar to those of other cld genes and that of fepE, thought to be part of the enterobactin iron uptake system of E. coli. The predicted proteins are compared with rfb-associated chain length determinants as a family of related genes.
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PMID:A plasmid-borne O-antigen chain length determinant and its relationship to other chain length determinants. 753 5

Nitric oxide (.NO) is synthesized by the enzyme nitric oxide synthase (NOS). There are 2 constitutive forms of NOS (cNOS) and 1 inducible form (iNOS). Cells containing cNOS rapidly and transiently produce small amounts of NO in response to agonists that raise cytosolic levels of free Ca2+, whereas cells expressing inducible iNOS produce large amounts of .NO for extended periods after a lag of several hours during which time the enzyme is induced. Until recently, the 2 constitutive isoforms of NOS were thought to be confined to endothelial cells (eNOS) and brain (bNOS or nNOS). However, eNOS and bNOS have been identified in an increasing variety of additional cells. Many, if not most, types of cells are capable of expressing iNOS in response to cytokines, endotoxin, and phagocytosis. Regulation of iNOS occurs at transcriptional, translational, and posttranslational levels. Because .NO is rapidly diffusible and soluble in hydrophobic and aqueous environments, it is well suited to its role as an intercellular messenger with the unique ability to penetrate solid tissue. However, it is rapidly inactivated by hemoglobin. The biochemistry of .NO is dominated by its rapid reaction with oxygen and transitional metals, notably iron. The former reaction may be protective, as when neutralizing superoxide (.O2-), or harmful in forming additional highly damaging radicals such as peroxynitrite. Interaction of .NO with iron-containing proteins has a number of sequelae, including the activation of guanylate cyclase, inhibition of mitochondrial respiration, and inhibition of cell division. Nitric oxide has been implicated in a number of conditions of orthopaedic interest, including inflammation, arthritis, osteoporosis, sepsis, ligament healing, and aseptic loosening of joint prostheses.
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PMID:Nitric oxide and its role in orthopaedic disease. 754 92

Serum triglyceride levels are significantly higher and serum high-density lipoprotein cholesterol levels are lower in patients with gout compared with healthy individuals. Whereas increased serum triglyceride levels exist intrinsically in gout, serum uric acid concentration correlates inversely with insulin sensitivity and positively with serum triglycerides. Interaction of monosodium urate crystals with granulocyte-macrophage colony-stimulating factor and with tumor necrosis factor-activated neutrophils favored the production of interleukin-1 over that of interleukin-1-Ra, resulting in a proinflammatory imbalance. Interaction of the crystals with iron or tyrosine kinase may modify their inflammatory response and can be an important modulating mechanism in gouty arthritis. E-selectin is a specific marker for synovial fluid soluble endothelial activity and is increased in the synovial fluid of patients with gouty arthritis, as well as in that of patients with other inflammatory arthritides. Similarly, E-selectin was found to be high in joints with monosodium urate crystal-induced synovitis. In addition, synovial fluid levels of interleukin-8 were found to be high in gout, rheumatoid arthritis, and osteoarthritis.
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PMID:Gout, uric acid metabolism, and crystal-induced inflammation. 754 16

This paper presents a review of the significant body of literature liking dietary iron overload, not only to heart disease, but also to cancer, diabetes, osteoporosis, arthritis, and possibly other disorders. Following an analysis of our understanding of the mechanistic role iron plays in oxidative damage, an interpretation of the fact that plasma concentrations of several antioxidants are decreased in the presence of disease is offered. Evaluation of (1) age-related dietary trends over time and (2) factors involved in iron absorption leads to the hypothesis that the combination of citric acid and ascorbic acid (a synergistic pair of strong enhancers) is instrumental in causing a deleterious increase in iron load in aging populations. Iron overload may be the most important common etiologic factor in the development of the diseases mentioned; therefore, the synergistic combination of citric and ascorbic acids may play a major role in our worsening disease statistics. Evidence to support this hypothesis and possible experiments to test it are included. This combination needs further study, particularly because the iron overload produced may be correctable.
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PMID:Proposed role for a combination of citric acid and ascorbic acid in the production of dietary iron overload: a fundamental cause of disease. 755 10


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