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ID PMID Title PublicationDate abstract
1606726 Limiting-dilution analysis of T cell reactivity to mycobacterial antigens in peripheral bl 1992 Jun Limiting-dilution analysis (LDA) was used to quantify the frequency of Mycobacterium bovis BCG- and 65-kD-reactive T cells in paired samples of peripheral blood and synovial tissue from patients with rheumatoid arthritis. The frequency of BCG-reactive T cells detected in the peripheral blood of patients ranged from 1/585 to 1/7639 versus a control frequency range of 1/480 to 1/6773. The frequency of such cells in the synovium was found to be much lower than it was in peripheral blood; in fact, in 80% of patients synovial BCG-reactive T cells were not detected. The frequency of 65-kD-reactive cells in the peripheral blood of each individual was lower than the frequency of BCG-reactive cells (range 1/3738 to 1/55,324), as would be expected. However, no synovial 65-kD-reactive cells were detected from any of the patients studied. The LDA assay for the 65-kD antigen was consistent with the single hit model, that for BCG was not. The relatively high proportion of mycobacterial-reactive precursors seen in the peripheral blood of non-vaccinated individuals may reflect a population of cells induced either by natural environmental exposure to mycobacteria or, given the highly conserved nature of heat shock proteins across phylogeny, by some other infection. The results also suggest that the frequent finding of reactivity to proteins such as the 65-kD heat shock protein contained within BCG may not be a generalized phenomenon in rheumatoid synovium.
8461924 Physiological variations in the urinary excretion of pyridinium crosslinks of collagen. 1993 Apr To further validate measurements of the pyridinium crosslinks of collagen as indices primarily of bone resorption in arthritis and other diseases, the effects of day-to-day and nyctohemeral parallel variations, and of renal impairment have been studied. Day-to-day variations measured over 3 weeks were between 16 and 24% for a group of post-menopausal women. Nyctohemeral variations in crosslink excretion of 10-15% were recorded. Although crosslink excretion relative to creatinine was generally higher in the morning than in the evening, no consistent pattern was observed between healthy male and female volunteers and a group of patients with OA or RA. For patients with impaired renal function, with or without arthritis, there was no correlation between crosslink excretion and either creatinine clearance rates or urinary N-acetyl glucosaminidase activity. These results suggested that there was no direct relationship between renal function, at the glomerular or tubular level, and crosslink excretion.
8100700 Receptor expression in synovial fluid neutrophils from patients with rheumatoid arthritis. 1993 May OBJECTIVES: The aim of this study was to determine if neutrophils isolated from the blood and synovial fluid of patients with rheumatoid arthritis had patterns of receptor expression resembling those of blood neutrophils from controls which had been activated and primed in vitro. METHODS: Fluorescence activated cell sorting was used to measure receptor expression in paired blood and synovial fluid neutrophils from patients and in control neutrophils exposed to phorbol myristate acetate and granulocyte-macrophage colony stimulating factor. RESULTS: There was no significant difference in the patterns of receptor expression in blood neutrophils from patients and healthy controls, but neutrophils in the synovial fluid had been primed and activated within the joint. About 50% of rheumatoid synovial fluid neutrophil samples expressed Fc gamma RI, a high affinity receptor for monomeric IgG, which is only expressed in neutrophils exposed to cytokines. CONCLUSIONS: Synovial fluid neutrophils are activated and primed within the inflamed joint and hence their ability to respond to activating factors such as immune complexes will be modulated. As the expression of Fc gamma RI requires active biosynthesis, this work indicates that selective gene activation occurs when neutrophils are recruited into rheumatoid joints.
8308324 Covert multi-focal infective arthritis. 1993 Nov Six patients with pre-existing rheumatic joint disease presented with overwhelming septicaemia but without overt signs of joint inflammation. Joint aspirates demonstrated multifocal staphylococcal infective arthritis. Despite intensive care all six died from the infection or its immediate sequelae. The contrast between this clinical entity and classical infective arthritis, presenting with one or more swollen, tender joints, is discussed.
7685228 Reversal of gold-induced neutropenia with granulocyte colony-stimulating factor (G-CSF). 1993 Jun We have successfully overcome severe neutropenia in an RA patient treated with gold salts, using granulocyte colony-stimulating factor (G-CSF), reducing the duration of neutropenia and risk of infection. The patient suffered no side effects, and use of G-CSF represents an important addition to the management of a life-threatening drug reaction.
7785501 Immunoglobulin gene expression in rheumatoid arthritis. 1995 Rheumatoid arthritis (RA) is characterized by inflammation of synovium, in which immunoglobulin-secreting plasma cells are generally present. The forces driving immunoglobulin expression in RA synovium are unknown. Sequences of VH and VK transcripts from an RA synovial cDNA library demonstrate patterns of somatic mutation typical of an antigen-driven response. Moreover, 5% of the kappa repertoire appears to derive from the same B cell progenitor, suggesting an oligoclonal response. Immunoglobulin expression in this synovium thus appears to result from antigen stimulation. In addition, this patient's synovium is enriched for unusually long VK-JK joins (CDR3s), suggesting abnormal selection or regulation of the B cell response in RA.
8961379 Analysis of bcl-2+ lymphocyte subpopulations in inflammatory synovial infiltrates by a dou 1996 We used a double-immunostaining technique to analyze the distribution of bcl-2+ B and T lymphocytes within the synovial membranes (SM) of 13 patients with rheumatic diseases: 11 with rheumatoid arthritis (RA), 1 with ankylosing spondylitis (AS), and 1 with osteoarthritis (OA). A high proportion (up to 50%) of the lymphocytes belonged to the B cell subset. Most of both T and B lymphocytes were positive for the bcl-2 protein. In germinal centers B lymphocytes were also negative for bcl-2 protein expression, comparable to the situation in germinal centers of secondary lymphatic organs. We conclude that bcl-2- B lymphocytes are submitted to antigen selection in the inflamed SMs while bcl-2 protein expression provides survival signals for their persistence in the infiltrates. The expression of bcl-2 may be an important factor in protecting lymphocytes in SM from apoptosis by glucocorticoids, cytostatic drugs, and irradiation.
7938489 [Value of direct radiographic enlargement (DIMA) in early detection of rheumatic inflammat 1994 Jul Rheumatological joint disorders were examined with mammographic film-screen combinations and high-definition microfocal magnification radiography. Our objective was to evaluate the potentials of magnification radiography in diagnosing arthritis by means of interobserver and ROC analysis. The microfocal X-ray unit had a spot size of 20-130 microns; 5-fold magnification was performed. Digital luminescence radiography was employed; digital image processing included simulation of conventional technique and edge enhancement. Eighty radiographs were obtained with conventional and magnification technique. All films were analyzed by five readers. Anatomical and pathological structures were evaluated. The percentage of uncertain findings in magnification radiography was lower compared to conventional radiographs (14% to 26%); in 8% (compared to 19%) the diagnosis of erosions was uncertain. Additionally ROC analysis was carried out. Magnification radiography was significantly (p < 0.03) better than the conventional films.
1418020 Presence of small proteoglycan fragments in normal and arthritic human cartilage. 1992 Sep OBJECTIVE: To characterize the small proteoglycans decorin and biglycan in normal human patellar cartilage and in cartilage from individuals with chronic polyarthritis. METHODS: Cartilage extracts were chromatographed on DEAE-Trisacryl and further separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis before and after enzymatic degradation of the glycosaminoglycan chains. Decorin and biglycan were visualized after Western blotting, using core protein-specific polyclonal and monoclonal antibodies. RESULTS: Core protein fragments of both proteoglycans were observed even in normal cartilage. In the case of decorin they amounted to up to 15% of the immunoreactive material, and up to 5% of the core protein was glycosaminoglycan free. The quantity of decorin core protein was reduced in arthritic cartilage, but the core protein fragments represented up to 45% of the immunoreactive material. Different zones of cartilage differed in their content of the fragments. Evidence for an increased proportion of biglycan fragments was not obtained. CONCLUSION: Chronic polyarthritis leads to increased degradation of small proteoglycans. A considerable proportion of decorin fragments is retained in the tissue. These alterations may have a negative influence on the mechanical stability of tissue.
8821503 [Avellis syndrome in systemic rheumatoid vasculitis]. 1995 Oct A 74-year-old man presented sudden onset hoarseness and dysphagia. Two months before this event, he had developed arthralgia of the shoulders, elbows, hands and foot and pleuritis which had been alleviated by a treatment with prednisolone. On admission, the patient could not phonate nor swallow at all. His soft palate was elevated at the right side. The uvula moved left when the patient tried to speak. Laryngoscopic examination revealed the paralysis of right vocal cord. The erythrocyte sedimentation rate (79mm/1h), C-reactive protein (5.3mg/dl), rheumatoid factor (310 IU/ml) and Clq-binding immune complex (4.5 micrograms/ml) were elevated. Hepatitis C virus antibody titer was more than 10.8 IU/l. Anti-nuclear antibody was 1:20 (normal < 1:20) and anti-neutrophil cytoplasmic antibody (p-ANCA) was positive. Blood study also revealed the evidences of hemolytic anemia and hypoproteinemia. Hepatitis B virus markers, cryoglobulin, anti-ds DNA, anti-Sm, anti-RNP, anti-SS-A, anti-SS-B antibodies were negative. Magnetic resonance imaging of the brainstem was normal. A sural nerve biopsy revealed patchy demyelination of the fascicles. The teasing of nerve fibers showed segmental demyelination. Chest X-ray showed the interstitial pneumonia and pleuritis in the right lower lung. Otological examination revealed the bilateral secretory otitis media. A treatment with high dose prednisolone, ciclosporin and cyclophosphamide was partially effective. However we could not continue these medication because of the induction of liver damage. The patient died of multi-organ failure around a year after the emergence of aphonia and dysphagia. The autopsy specimen of the right vagus nerve showed the similar patchy damage of nerve fibers as was observed in the biopsied sural nerve. The present case was diagnosed as systemic rheumatoid vasculitis. The syndrome of aphonia and dysphagia due to paralysis of the unilateral soft palate and vocal cord is called Avellis syndrome. This syndrome has been reported mainly in relation with the infarction of lateral medulla. The present case shows that Avellis syndrome can be produced by mononeuritis of the vagus nerve.
7690781 The cytokeratin filament-aggregating protein filaggrin is the target of the so-called "ant 1993 Sep In rheumatoid arthritis (RA), the high diagnostic value of serum antibodies to the stratum corneum of rat esophagus epithelium has been widely reported. These so-called "antikeratin antibodies," detected by indirect immunofluorescence, were found to be autoantibodies since they also labeled human epidermis. Despite their name, the actual target of these autoantibodies was not known. In this study, a 40-kD protein (designated as 40K), extracted from human epidermis and specifically immunodetected by 75% of RA sera, was purified and identified as a neutral/acidic isoform of basic filaggrin, a cytokeratin filament-aggregating protein, by peptide mapping studies and by the following evidences: (a) mAbs specific for filaggrin reacted with the 40K protein; (b) the autoantibodies, affinity-purified from RA sera on the 40K protein, immunodetected purified filaggrin; (c) the reactivity of RA sera to the 40K protein was abolished after immunoadsorption with purified filaggrin; (d) the 40K protein and filaggrin had similar amino acid compositions. Furthermore, autoantibodies against the 40K protein and the so-called "antikeratin antibodies" were shown, by immunoadsorption experiments, to be largely the same. The identification of filaggrin as a RA-specific autoantigen could contribute to the understanding of the pathogenesis of this disease and, ultimately, to the development of methods for preventing the autoimmune response.
1385767 Kinetics of cytokine secretion by mononuclear cells of the blood from rheumatoid arthritis 1992 Jul Mononuclear cells from peripheral blood (PBMC) of rheumatoid arthritis (RA) patients and healthy controls were incubated with alpha-CD3. Cytokine secretion from 2 h to 72 h of incubation was measured by ELISA. There were no significant differences in secretion of T cell derived IL-2 and IL-4 in cultures from RA patients and controls. The macrophage-derived cytokines, IL-1 beta and tumour-necrosis factor-alpha (TNF-alpha) were secreted with a steep increase of concentration during the first 16 h of incubation by PBMC from RA patients. PBMC from healthy controls secreted both cytokines at a constantly rising rate with a maximum for TNF-alpha at 48 h and for IL-1 beta at 72 h. Interferon-gamma (IFN-gamma) is secreted in significantly reduced concentrations by PBMC from untreated RA patients compared with controls. Gold-salt treatment led to a slightly delayed and enhanced secretion of TNF-alpha and IL-1 beta, an enhanced secretion of IL-2 and a restored secretion of IFN-gamma.
8311555 Expression of basic fibroblast growth factor in synovial tissues from patients with rheuma 1994 Jan OBJECTIVE: The distribution and production of basic fibroblast growth factor (bFGF) was examined on the synovium from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: The localisation of bFGF was determined by an immunohistochemical staining procedure using anti-bFGF monoclonal antibody. The expression of bFGF mRNA was detected by nonradioactive in situ hybridisation using bFGF antisense oligo DNA. RESULTS: The bFGF was found in the synovial lining cell, sublining stromal fibroblast-like cells, and vascular endothelial cells from patients with RA and OA. Little or no bFGF was found in non-inflamed synovium. Immunostaining of bFGF in the synovial cells was more extensive and intense in synovium of patients with RA than that of patients with OA. The nuclei of the synovial lining cell layer were also immunostained. These nuclear staining were more intense in the lining cell layer from RA patients with moderate or severe proliferation of synovial cells than in RA patients with mild proliferation. The bFGF mRNA was also detected in the synovial lining cell layer of the inflamed synovium. CONCLUSION: The synovial lining cells produced bFGF. The proliferation of synovial cells in the inflamed joints may be the results of stimulation by the bFGF in autocrine manner.
1496989 HLA heterozygosity contributes to susceptibility to rheumatoid arthritis. 1992 Sep We have investigated the role of HLA-DR genotypes in 184 patients with severe rheumatoid arthritis (RA) and in 46 patients with Felty syndrome, to establish the relative contribution of the RA-associated subtypes of DR4 (Dw4, Dw14, and Dw15). There was an excess of DR4 homozygotes, particularly Dw4/Dw14 compound heterozygotes (relative risk [RR] 49). The risk associated with Dw4 depended on the other allele present--Dw4/DR1 (RR 21), Dw4/Dw4 (RR 15), and Dw4/DRX (RR 6). There was a significant risk from Dw4/Dw14 compared with Dw4/Dw4, both in those with severe RA (RR 2.9; P less than .02) and in those with Felty syndrome (RR 4.2; P less than .02). In contrast, in a further 63 known DR4 homozygotes with RA, not selected for severe disease, the excess of Dw4/Dw14 was much less striking (RR 1.4; not significant), suggesting that this genotype may be particularly associated with more severe disease. We also found four cases with the rare Dw4/Dw15 genotype (expected less than or equal to 0.5; P less than or equal to .02). Since the Dw4, Dw14, Dw15, and DR1 molecules have similar antigen-binding sites and since combinations of these alleles particularly predispose to severe RA, we suggest that synergistic mechanisms are involved. These could include an effect on T-cell repertoire selection.
7540479 Levels of circulating intercellular adhesion molecule-1 and -3 but not circulating endothe 1995 Apr The aim of this study was to investigate whether levels of circulating adhesion molecules reflect vascular inflammation in rheumatoid vasculitis (RV). Levels of circulating intercellular adhesion molecule-1 (cICAM-1), c-ICAM-3 and circulating endothelial leucocyte adhesion molecule (cE-selectin) were determined in 14 patients with RV and compared to 47 patients with rheumatoid arthritis (RA) and 100 healthy donors (HD). Enzyme-linked immunosorbent assays were used to quantify cICAM-1, cICAM-3 and cE-selectin. We found that in RV significantly (P < 0.0001) elevated levels of cICAM-1 and cICAM3, but not cE-selectin, were found when compared with RA patients. Levels > 2 S.D. above the mean level of HD were present for cICAM-1, cICAM-3 and cE-selectin in 57, 71 and 21%, respectively of patients with RV and 2, 21 and 44%, respectively of the RA patients. Increased levels of both cICAM-1 and cICAM-3 were found in 43% of the RV patients and in none of the RA patients. Comparison of the serum levels of patients studied in an active and inactive phase of RV revealed significantly lower levels of cICAM-3 levels in the inactive phase. In conclusion we find that determination of cICAM-1 and cICAM-3 may be useful as a marker of vascular inflammation in patients with RV.
8406258 Fatty acid composition of normal and atrophied heel fat pad. 1993 Sep Capillary gas-liquid chromatography was used to analyze the fatty acid composition of normal heel fat pads from subjects without systemic disease (N = 8) and atrophied heels from patients with diabetic peripheral neuropathy (N = 4), rheumatoid arthritis (N = 1), peripheral vascular disease (N = 1), and hereditary sensory neuropathy (N = 1). In the normal subjects, the fatty acid composition of subcutaneous abdominal fat was also obtained for comparison. Three saturated fatty acids (myristate, palmitate, and stearate) and four unsaturated fatty acids (palmitoleate, oleate, vaccenate, and linoleate) comprised over 90% of the total fatty acid composition. Higher percentages of unsaturated fatty acids and lower percentages of saturated fatty acids were found in the normal heel fat pads when compared to subcutaneous abdominal fat. The increase in the ratio of unsaturated fatty acids to saturated fatty acids (4.4 versus 2.5, P < .01) may decrease triglyceride viscosity and enhance the biomechanical efficiency of the heel fat pad. Though the number of patients is small, no statistically significant compositional differences were noted between the heel fat from normal subjects and from subjects with peripheral neuropathies, rheumatoid arthritis, or peripheral vascular disease. However, the heel fatty acid composition of the one subject with a hereditary sensory neuropathy was less unsaturated and more saturated than normal with a ratio of unsaturates to saturates similar to that of the abdomen (2.8).
7582710 Neurological side effects in two patients receiving gold injections for rheumatoid arthrit 1995 Oct We describe two patients who developed neurological side effects as part of the spectrum of nitritoid reactions. Both reactions occurred late in the course of treatment. The first patient developed mild nitritoid symptoms and pain in a band-like distribution, corresponding to T10-T12 dermatomes, shortly after gold sodium thiomalate (GSTM) injection. Further injections were followed by similar symptoms in addition to paraesthesiae and altered pin-prick sensation of anterior thigh and legs with no residual deficit. She has had no further episodes since substitution of aurothioglucose. The second patient experienced mild nitritoid symptoms following several GSTM injections prior experiencing a cerebrovascular accident within several hours of her next injection. She subsequently haemorrhaged into the infarcted area with residual neurological deficits. These cases highlight that nitritoid reactions can be severe and may be heralded by milder symptoms. Patients who develop these reactions whilst receiving GSTM can be successfully changed to aurothioglucose.
1735199 The Sauvé-Kapandji procedure. 1992 Feb In 1936, Sauvé and Kapandji described a procedure that included an arthrodesis across the distal radioulnar joint and created a pseudarthrosis of the ulna, proximal to the fusion, to restore pronation and supination. The author has used this technique because preservation of the head of the ulna minimizes the potential for some of the complications that can follow its excision. Retention of the head of the ulna would secure a more normal transmission of loads across the wrist, maintain full support to the carpal condyle and to the extensor carpi ulnaris tendon, and preserve the normal contour and appearance of the wrist. This paper presents the author's experience using this procedure in 37 wrists with rheumatoid arthritis, osteoarthrosis and posttraumatic changes of the distal radioulnar joint, and chondromalacia of the head of the ulna. This is a satisfactory operation, although not infallible. It is probably contraindicated when treating the unstable or frankly subluxed or dislocated distal radioulnar joint, ulna dorsal, a therapeutic problem for which there is no reliable solution. Indications for the Sauvé-Kapandji technique are discussed in relation to other operations frequently used for the distal radioulnar joint.
7703672 Pathogenic responses of bradykinin system in chronic inflammatory rheumatoid disease. 1994 Dec Excessive release of kinin (BK) in the synovial fluid can produce oedema, pain and loss of functions due to activation of B1 and B2 kinin receptors. Activation of the kinin forming system could be mediated via injury, trauma, coagulation pathways (Hageman factor and thrombin) and immune complexes. The activated B1 and B2 receptors might cause release of other powerful non-cytokine and cytokine mediators of inflammation, e.g., PGE2, PGI2, LTs, histamine, PAF, IL-1 and TNF, derived mainly from polymorphonuclear leukocytes, macrophages, endothelial cells and synovial tissue. These mediators are capable of inducing bone and cartilage damage, hypertrophic synovitis, vessel proliferation, inflammatory cell migration and, possibly, angiogenesis in pannus formation. These pathological changes, however, are not yet defined in the human model of chronic inflammation. The role of kinins and their interacting inflammatory mediators would soon start to clarify the detailed questions they revealed in clinical and experimental models of chronic inflammatory diseases. Several B1 and B2 receptor antagonists are being synthesized in an attempt to study the molecular functions of kinins in inflammatory processes, such as rheumatoid arthritis, periodontitis, inflammatory diseases of the gut and osteomyelitis. Future development of specific potent and stable B1 and B2 receptor antagonists or combined B1 and B2 antagonists with y-IFN might serve as a pharmacological basis for more effective treatment of joint inflammatory and related diseases.
7938822 [Bone marrow aplasia and gold salts. Review of the literature apropos of 2 cases]. 1994 Jul Bone marrow aplasia remains the most serious adverse effect with gold therapy. Its prevalence is still a controversial issue and at present it is not possible to give accurate figures on its frequency. Two patients diagnosed of rheumatoid arthritis are reported. They underwent chrysotherapy and developed bone marrow aplasia within a 2-month period of therapy. The pathogenic mechanism of blood dyscrasias secondary to gold salts is still unknown. The best available method in the prevention of this serious condition is the periodical obtention of complete blood counts.