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ID PMID Title PublicationDate abstract
7923921 Expression of granzymes A and B in synovial tissue from patients with rheumatoid arthritis 1994 Oct Granzymes A and B are serine proteinases which are stored in the granules of activated cytotoxic T cells and NK cells. Expression of these granzymes by cytotoxic cells in tissues can be used as an activation marker for these cells. To investigate a possible role of cytotoxic lymphocytes in rheumatoid arthritis (RA) and osteoarthritis (OA), we assessed the expression of granzymes A and B by cytotoxic lymphocytes in synovial biopsies from five RA and five OA patients using mAb specific for these serine proteinases. In three of the five RA patients but also in two of the five OA patients granzyme A- and B-expressing lymphocytes were observed in the synovium. Double-labeling immunohistochemical techniques revealed that up to 75% of the granzyme-positive synovial lymphocytes had the CD16+ or CD56+ natural killer cell phenotype. Less than 5% were CD3+, CD8+ cytotoxic T cells, whereas in some patients the phenotype of up to 50% of these cells could not be identified. The presence of granzymes A and B in the synovium of both RA as well as OA patients was confirmed on the molecular level in a second group of 11 RA and 5 OA patients using the polymerase chain reaction. Thus, expression of granzymes A and B occurs in the synovium in patients with RA as well as those with OA. These proteins are mainly expressed by NK cells that may therefore play a role in the pathogenesis of these diseases.
7732497 [Three cases with systemic rheumatic diseases who developed pulmonary lesions suggestive o 1995 Feb Three cases with systemic rheumatic diseases who developed lung diseases compatible with BOOP were reported. Underlying diseases of these patients were: RA (1 case), SLE (2 cases). Respiratory symptoms were observed in one case such as dry cough at the time of diagnosis of BOOP. Chest radiography showed multiple infiltrates in 2 cases, bilateral reticular shadow in one case. In one case characteristic finding described as wandering shadow was observed. TBLB was done in 3 cases. Pathohistological findings were compatible with BOOP. Repeated Bacteriological examinations failed to demonstrate specific organisms implicated for lung lesions. Cytological studies of sputum and TBLB specimens were all negative for malignancy. Antibiotic agents including anti-tuberculosis drugs were not effective for pulmonary diseases. Moderate doses of prednisolone were effective in 3 cases. Although the open lung biopsy has been recommended for establishment of diagnosis of BOOP, in patient with systemic rheumatic diseases this invasive procedure is not always easily performed. Further characterizations of clinical and laboratory features are indicated for noninvasive diagnosis of BOOP.
1466602 Sequence similarity between HLA-DR1 and DR4 subtypes associated with rheumatoid arthritis 1992 Nov Rheumatoid arthritis (RA) is found more often in subjects carrying the HLA-DR1 antigen and some subtypes of the HLA-DR4 antigen than in those without these antigens. Analysis of probes specific for HLA-DR4 has shown that amino acids encoding positions 69-74 (EQRRAA) of the beta chain indicates susceptibility to RA. A hexamer sequence of proteus haemolysin spanning residues 32-37 (ESRRAL) has been identified which resembles biochemically, and discriminates by charge, between HLA types associated with RA (DR1, Dw4, Dw14, Dw15), and those not linked with the disease (Dw10, Dw13).
8568276 IgM rheumatoid factors react with human class I HLA molecules. 1996 Feb 15 Half of 30 human polyclonal IgM rheumatoid factors (RF) showed positive ELISA reactions with affinity-isolated human class I molecules (A2 and B7). Positive RF reactivity with isolated class I heavy chains indicated that anti-class I RF interaction did not merely reflect RF anti-beta 2m specificity. Cross-reactions between antigenic determinants on human IgG, class I molecules, and beta 2m reacting with RF could be demonstrated by ELISA inhibition. When gene products of A2 alpha 2 exons 2, 3, and 4 were synthesized as overlapping heptamers on polypropylene pins, six RF-reactive epitopes within solvent accessible class I HLA regions were identified: EPRAPWI, QEGPEYW, QTHRVDL (second A2 exon), EQLRAYL, GTCVEWL, and WLRRYLE (third A2 exon). Glycine-alanine substitution for each residue within these RF-reactive sites identified R48, W51, E55, Y107, R108, W147, Q155, and E172 as immunodominant residues for RF reactivity. Many of these RF-reactive class I regions also showed positive ELISA reactions with monoclonal human IgM RFs derived from rheumatoid arthritis synovial B cells. Whole serum from patients with rheumatoid arthritis showed a spectrum of IgM, IgA, and IgG Abs that adsorbed to and could be eluted from monomeric IgG or HLA A2 affinity columns. Normal serum similarly analyzed showed only trace reactions with IgG, A2, or beta 2m. Flow cytometry using RF incubated with A2 cell lines showed definite immunofluorescence reactivity with cell membranes not observed with normal non-RF IgM. Reactivity of human IgM RF with determinants on class I molecules may reflect antigenic overlap within several members of Ig gene superfamily products.
8273544 Impaired activity of thiol-dependent ATPases in rheumatoid mononuclear cell membranes. 1993 Ion-motive ATPase play an essential role in many aspects of cell biology, including mononuclear cell (MNC) functions relevant to chronic inflammation. For example, ouabain, a specific inhibitor of Na+, K+ ATPase, suppresses both T and B cell proliferation but induces synthesis of IL-1. Using a cytochemical assay quantified by microdensitometry, total and ouabain-sensitive ATPase activities have been compared in MNC from rheumatoid and control subjects. The sensitivity of these enzymes to inactivation by thiol-blocking reagents has been studied by preincubation with an impermeant SH blocker p-hydroxymercuriphenylsulphonate (pHMPSA). The results show that rheumatoid MNC have significantly impaired ATPase activity compared to healthy cells and that both total and ouabain-sensitive ATPase activities are readily inhibited by pHMPSA. The depressed ATPase activity in rheumatoid MNC could thus be due to blockade/oxidation of a reactive surface thiol, and could contribute to perpetuation of the chronic inflammatory process in these patients.
8335895 Detection of glycosylation abnormality in rheumatoid IgG using N-acetylglucosamine-specifi 1993 Jul 15 Although the galactose deficiency in the Asn297-linked sugar chains of serum IgG from patients with rheumatoid arthritis (RA) has been established, structural analysis of sugar chains has not been readily available. Psathyrella velutina lectin (PVL) preferentially interacts with the N-acetylglucosamine beta 1-->2Man group, exposed at the termini of sugar chains in agalacto IgG. Biotinylated PVL reacted strongly in Western blotting with H chains of IgG derived from patients with RA. An ELISA-based assay for the detection of agalacto IgG was developed using recombinant protein G and biotinylated PVL in combination, and the screening of patients' sera was performed. PVL binding of serum IgG significantly correlated with percentage of galactose-deficient IgG determined by the structural analysis. Age-related slight increase in PVL binding was observed among normal controls. Patients with RA showed significantly higher PVL binding (37.90 +/- 42.25 U/ml, n = 93) as compared with normal controls (5.75 +/- 2.92 U/ml, n = 112) (p = 0.0001). Patients with SLE showed lower but still significant PVL binding (17.86 +/- 5.18 U/ml, n = 10, p = 0.0001). PVL binding correlated with C-reactive protein level in serial analysis of individual RA patients, and was significantly higher in the synovial fluid compared with paired serum samples. PVL binding assay may provide an ideal tool for the simple and sensitive detection of agalacto IgG.
1359695 Influence of synovial cells on cartilage in vitro: induction of breakdown and inhibition o 1992 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.
8220935 Immunoassay of platelet-derived growth factor in the plasma of patients with scleroderma. 1993 Nov It has been postulated that platelet-derived growth factor (PDGF) is responsible for the abnormal fibroblast proliferation observed in scleroderma. In one previous study, plasma samples from patients with scleroderma caused increased mitogenesis in cultured fibroblasts, suggesting that the pathogenesis of scleroderma is related to increased plasma PDGF concentrations. To test this hypothesis, we used a sensitive, monoclonal antibody-based ELISA to measure PDGF in the plasma of 12 scleroderma patients. A rigorous sampling protocol prevented false elevations in plasma PDGF levels from ex vivo platelet degranulation: beta-thromboglobulin concentrations were measured in each plasma sample to monitor platelet lysis. Plasma PDGF concentrations in the scleroderma patients were not statistically different from those observed in age- and sex-matched normal controls, and patients with RA. While it is possible that changes in PDGF activity at a local level alter fibroblast function, we cannot conclude that elevated plasma concentrations of PDGF play a role in the pathogenesis of scleroderma.
1469009 Fractures adjacent to humeral prostheses. 1992 Dec In a review of records and radiographs from 1974 through 1988, we identified seven patients who had a humeral fracture after either a total shoulder replacement or a shoulder hemiarthroplasty. All seven patients had complications after the fracture, and five fractures did not unite until an operation was done. All of the fractures that were treated operatively healed without sequelae. Four patients who were managed operatively had satisfactory relief of pain and one had fair relief. One patient who had a non-union refused further treatment for medical reasons. The one fracture that united without operative treatment healed with the tip of the prosthesis outside of the humeral shaft, but persistent pain led to a revision total shoulder replacement. The average time to union after the operation was approximately five months (range, four to seven months). There was a permanent decrease in the motion of the shoulder from preinjury levels in five of the six patients who had union of the fracture.
1314103 Hemorrhagic cystitis with herpes simplex virus type 2 in the bladder mucosa. 1992 Mar A 67-year-old woman who had underlying rheumatoid arthritis and diabetes mellitus had an 8-year history of recurrent hemorrhagic cystitis. During her most recent episode of cystitis, a specimen of urine yielded herpes simplex virus type 2 in culture. A biopsy of the bladder mucosa revealed intranuclear inclusions in multinucleated and mononuclear giant cells that were positive for herpes simplex virus type 2 by immunoperoxidase staining. She had no evidence of infection with herpes simplex virus outside her bladder.
1282008 Inhibition of synovial fluid T cell proliferation by anti-CD5 monoclonal antibodies. A pot 1992 Dec OBJECTIVE: Monoclonal antibodies (MAb) directed against the T cell surface molecule CD5 are able to provide accessory stimulatory signals to resting T cells. The potential role of CD5 as an immunoregulatory molecule in inflammatory synovitis was examined. METHODS: Synovial fluid and peripheral blood T cells of patients with active rheumatoid arthritis (RA) were purified and stimulated with interleukin-2 (IL-2), and the effect of MAb directed against CD5 on IL-2 responsiveness was examined. RESULTS: IL-2-induced proliferation of synovial fluid T cells was strongly inhibited by anti-CD5 MAb, but not by anti-CD28 or anti-CD3 MAb. In RA peripheral blood T cells, MAb directed against CD5, CD3, and CD28 induced IL-2-dependent T cell growth, similar to findings in healthy controls. The difference in activity of anti-CD5 MAb on synovial fluid T cells compared with peripheral blood T cells was not due to different surface expression of CD5. CONCLUSION: Anti-CD5 has an inhibitory effect on in vivo-activated synovial fluid T cells. The disease-ameliorative effects of anti-CD5 immunotoxin treatment of RA may be partly due to "switching-off" of T cell activation in the joints.
8701242 [Expenses and risk of artificial knee joint: a look backward to a 20-year clinical experie 1996 Jun 15 Costs and risks of implantation of prosthetic knee joints are analyzed in this retrospective study. From 1974-1993 514 primary and 34 revision arthroplasties were done in this hospital, all by the same surgeon. 98% of the patient protocols were available and analyzed, but no systematic follow-up was attempted. 82% of the patients were female; mean age at operation was 74 years. Joint destruction was caused by osteoarthritis in 75%, aseptic osteonecrosis in 10%, rheumatoid arthritis in 9% and posttraumatic arthritis in 3.5%. 75% of the patients were obese and had a body mass index > 25 kg/m2. Non-constrained unicompartmental type prostheses were used in 66%, the non-constrained multicompartmental type in 10% and the constrained total rotation knee (Engelbrecht) in 24%. Hospital mortality rate was 0.55% due to myocardial infarction and pulmonary embolism. 3 patients died of septic prosthetic joint infections 5, 7 and 71/2 years after surgery. Perioperative morbidity, typical of the age group above 70 years, was mainly due to cardiovascular and thromboembolic events and gastrointestinal bleeding. Early infection during the first postoperative year was encountered in 3 constrained total knees, but none in nonconstrained type. The calculated operative infection rate was 2.4% for the constrained type, zero for the non-constrained type, and 0.5% for the whole series. Late prosthetic infections occurred in 8 patients up to 12 years after surgery. In comparing non-constrained unicondylar and hinged types of joint replacement, the non-constrained sledge prosthesis involves considerably lower costs in terms of duration of surgery, hospital stay, blood loss, price of the implant, infection rate and difficulties of revision arthroplasty. Lower costs and risks favour the smaller unicondylar implant for use in localized degenerative or necrotic destruction, particularly of the medial compartment of the knee. Semi-constrained total condylar systems are used for more extensive degeneration without evident instability. The indication for hinged endoprostheses is restricted to revision arthroplasty and grossly unstable knees.
8578891 [Cutaneous side-effects of nonsteroidal anti-inflammatory drugs (NSAID)]. 1995 Nov NSAID are able to induce cutaneous side-effects by both systematical and topical application. Nearly all kinds of exanthema are possible by any type of these drugs. However, particular substances are more likely to induce certain drug eruptions; aspirin and indometacine may induce urticarial reactions, whereas piroxicam can lead to phototoxic or photoallergic dermatitis. Contact dermatitis induced by topical NSAID is still rare but increasing. Ketoprofen and bufexamac were major contact allergens based on the number of reports, but local differences among different countries were observed. The diagnosis of drug reactions, especially in systemic drugs, remains a problem because reliable in vitro methods are not yet in use and skin test procedures do not work in most cases. Therefore, the case history is still the most useful tool in evaluating anamnestic allergic events. Prospective studies of drug compatibility as well as an improvement of side-effect reports are necessary to assess specific risks for several drugs.
7533682 Decreased levels of complement receptor 1 (CD35) on B lymphocytes in persons with HIV infe 1995 Apr Previous studies have shown that complement receptor 1 (CR1) expression on erythrocytes is decreased under several conditions including HIV infection and autoimmune diseases. The goal of this study was to determine whether expression of CR1 on peripheral blood B cells, where this receptor plays a role during immune responses, is altered in persons with HIV infection. The B cells from rheumatoid arthritis (RA) patients were also assessed since this represents a group with known complement and B cell abnormalities. The CD19+ B cells from persons with either HIV infection or RA had significantly reduced levels of CR1 when compared with control donors (75 and 72% CR1+ versus 94% CR1+ for control donors). The reduction of B cell CR1 occurred in both the percentage of B cells positive for CR1 and the levels of CR1 found on positive cells. In contrast, CR1 on monocytes was not reduced. As shown in previous studies, CR2 was also found to be reduced on B cells from the HIV-infected persons and there was extensive overlap between the B cell subsets which lacked expression of CR1 and CR2. The complement receptor-negative B cells found in HIV-infected persons were not immature or activated as defined by their lack of expression of CD10 or B7, respectively. Elevated levels of C4d, a classical complement pathway-activation product, were detected in plasma from both HIV-infected and RA patients. These studies suggest that chronic complement activation occurring in persons with HIV infection or RA can affect the complement receptor phenotype of peripheral blood B cells. Since complement receptors are involved in activation of B cells, the subset that lacks CR1 may represent cells that have encountered immune complexes and may therefore be stimulated. Additionally, the downregulation of complement receptors may have significant effects on the ability of B cells to capture and present opsonized antigens.
7739185 [A necrobiotic nodule indistinguishable from lung adenocarcinoma]. 1995 Mar A 43-year-old woman was referred for examination because of an abnormal shadow on a chest X-ray film. She had a 12-year history of seropositive rheumatoid arthritis. Chest X-ray films and CT scans showed a pleurabased solitary nodule without a cavity. Cytological examination of a transbronchial biopsy specimen did not lead to a diagnosis, so thoracoscopic enucleation was performed. Histologically, the nodule consisted of lymphocytes and fibroblasts surrounding a central necrotic area, which indicated that it was a rheumatoid nodule. This solitary necrobiotic nodule was radiographically indistinguishable from lung adenocarcinoma, so histologic confirmation was necessary.
8310089 Dermatologic manifestations of rheumatic disorders. 1993 Dec Many rheumatic disorders have cutaneous lesions and sometimes skin lesions are the initial or most problematic manifestation of a patient's rheumatic disease. Many of the skin lesions encountered in these disorders are rather nonspecific. Other lesions, however, have characteristic and sometimes specific gross or histopathologic findings that often help the clinician diagnose the underlying rheumatic disease process. Additionally, drug-induced skin diseases are often encountered in patients being treated for rheumatic disease.
1620534 Radiographic evaluation of the degenerative cervical spine. 1992 Jul Despite some claims to the contrary, the use of plain film radiography can be an inexpensive initial means of evaluating the degenerative cervical spine if viewed in the context of the patient's clinical history and physical examination and may serve as a guide for further imaging techniques. This article presents a systematic approach for evaluating cervical spine radiographs for the spectrum of degenerative changes, followed by a brief discussion of differential diagnoses.
8737721 Different cytokine profiles in the synovial fluid of patients with osteoarthritis, rheumat 1996 Mar OBJECTIVE: Cytokines play a critical role in the pathogenesis of arthritis. The aim of this study was to compare the amounts of IL-1 alpha, IL-1 beta, IL-4, IL-6, IL-8, IL-10, IL-12, TNF-alpha, TGF-beta 1 and IFN-gamma in the synovial fluid of 30 patients with rheumatoid arthritis (RA), 40 patients with osteoarthritis (OA) and 13 patients with seronegative spondylarthropathies (SpA). METHODS: Since some samples exhibited non-specific activities, all cytokines were measured by ELISA in the presence or absence of cytokine specific neutralizing antibodies. RESULTS: Our data show that these cytokines can be detected in OA, RA and SpA. Compared to patients with OA, all cytokines were found in higher levels in patients with RA and SpA. Surprisingly, higher levels of IL-4, IL-10 and TGF-beta 1 were not associated with lower cytokine levels. In contrast, higher levels of IFN-gamma were associated with elevated monokine concentrations. CONCLUSIONS: Our data indicate that the immunosuppressive effects of IL-4, IL-10 and TGF-beta 1 predicted from in vitro studies may not be active in vivo. Different monokine profiles could be observed in patients with IL-4 and/or IFN-gamma, indicating that the T cells involved in these diseases may have different immunoregulatory properties.
8660101 Changes in (markers of) bone metabolism during high dose corticosteroid pulse treatment in 1996 May OBJECTIVE: To examine the effect of high dose corticosteroid pulse treatment (three times 200 mg dexamethasone intravenously in eight days) on calcium and bone metabolism in 17 consecutive patients with active rheumatoid arthritis (RA). METHODS: Bone formation was quantified by measurement of serum alkaline phosphatase, osteocalcin, and carboxyterminal propeptide of type I procollagen (pro-I-CPP) concentrations. Bone resorption was measured by urinary excretion of calcium, hydroxyproline, (free and total) deoxypyridinoline (Dpyr), (free and total) pyridinoline (Pyr), and serum concentrations of the carboxyterminal cross linked telopeptide of type I collagen (I-CTP). Disease activity of RA was measured by erythrocyte sedimentation rate, C reactive protein, and Ritchie and Thompson joint scores. RESULTS: Disease activity was initially high, and decreased during corticosteroid pulse treatment and the following five weeks. Osteocalcin, alkaline phosphatase, and pro-I-CPP concentrations were initially within normal limits, while I-CTP, Dpyr, and Pyr were increased. Osteocalcin and pro-I-CPP concentrations decreased (p < 0.01) during corticosteroid pulse treatment, but rapidly returned to baseline after the treatment. No changes were observed in alkaline phosphatase and urinary excretion of calcium and hydroxyproline. Bone resorption measured by serum I-CTP and urinary excretion of Pyr and Dpyr was unchanged or decreased (p < 0.05-0.01), depending on the time of measurement and the parameter measured. CONCLUSIONS: In these patients with active RA, bone resorption was increased, while bone formation was within normal limits. During high dose corticosteroid pulse treatment, bone formation was only transiently decreased, while markers of bone resorption were unchanged or decreased. Because corticosteroid pulse treatment has only a short term negative effect on bone formation, and because it probably reduces bone resorption, at least partly as a result of the decreased disease activity, the effect of corticosteroid pulse treatment on bone may be assumed to be relatively mild.
8484697 Gold induced nephropathy in rheumatoid arthritis and HLA class II genes. 1993 Apr OBJECTIVES: To elucidate the role of HLA-DRB, -DQA, and -DQB genes in patients with rheumatoid arthritis (RA) who developed gold induced nephropathy. METHODS: Southern blot analysis of HLA-DRB, -DQA, and -DQB genes was performed on DNA from 27 patients with RA with gold induced nephropathy, 37 patients with RA who were treated with gold but did not develop nephropathy, and 122 ethnically matched normal subjects. RESULTS: The 4.7 kb DQA1/Taq I band associated with DQA1*0501 and DR3 and DR5 was found in 16 (59%) patients with gold induced nephropathy compared with five (14%) patients without gold induced nephropathy. CONCLUSION: It is concluded that HLA-DQA region genes may be an important susceptibility factor for the development of gold induced nephropathy in patients with RA.