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ID PMID Title PublicationDate abstract
8528899 The anticytokine neuropeptide alpha-melanocyte-stimulating hormone in synovial fluid of pa 1994 Sep The aim of this study was to determine if the anticytokine neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) occurs, along with interleukin 1 receptor antagonist (IL-1ra) and soluble tumor necrosis factor receptor (sTNFr), in synovial fluid of patients with rheumatoid arthritis (RA), juvenile chronic arthritis (JCA), or osteoarthritis. The data show that alpha-MSH does occur in the synovial fluid and its concentrations are greater in patients with RA than in those with osteoarthritis. Synovial fluid concentrations of IL-1ra and sTNFr were likewise greater in RA. Further, concentrations of alpha-MSH, IL-1-ra, and sTNFr were greater in patients with polyarticular/systemic-onset JCA than in those with pauciarticular disease, that is in patients with greater joint inflammation. Concentrations of alpha-MSH were greater in synovial fluid than in plasma in a substantial proportion of patients, suggesting local production of the peptide; this is the first indication that the anticytokine molecule alpha-MSH is produced within a site of inflammation. Further, it appears that local production of alpha-MSH is induced particularly in those arthritic joints that have more intense inflammatory reactions. This finding, combined with previous evidence of the marked anti-inflammatory activity of alpha-MSH, suggests that the peptide acts locally to modulate proinflammatory influences in rheumatic diseases.
7720126 [Effects of tripchlorolide (T4) of Tripterygium wilfordii Hook on the proliferation of per 1994 Oct Tripchlorolide (T4) is a single active ingredient recently isolated from Tripterygium wilfordii Hook. The effects of T4 on the proliferation of peripheral blood mononuclear cells (PBMC) of rheumatoid arthritis (RA) patients and normal subjects were studied, RA patients and sex- and age-matched normal subjects (each 8 cases) were selected. PBMC were incubated with T4 of various doses (10, 20, 30 and 40 ng/ml) in the presence or absence of PHA for 72 hours. The results were as follows: T4 remarkably inhibited the proliferation of both PHA-stimulated and unstimulated PBMC of normal subjects and PHA-stimulated PBMC of RA patients as measured by MTT colormetric method. However, T4 showed a biphasic reaction in unstimulated PBMC of 3 RA patients. These results indicates that T4 would be useful in the therapy of RA. The significance of biphasic reaction occurring in RA patients needs to be further investigated.
7535212 The rheumatoid arthritis-associated autoantibodies to filaggrin label the fibrous matrix o 1995 Apr Since they were first described, serum IgG antibodies to the stratum corneum of rat oesophagus epithelium, highly specific for rheumatoid arthritis (RA), have been consensually called antikeratin antibodies (AKA). However, we recently demonstrated that they actually recognize three new proteins of rat oesophagus epithelium distinct from cytokeratins, and also human epidermal filaggrin. In this work we provided further evidence that AKA and RA-associated anti-filaggrin autoantibodies are the same antibodies. Moreover, analysing by indirect immunofluorescence on human skin a large series of 212 well characterized RA sera and anti-filaggrin autoantibodies purified from RA sera by affinity chromatography, we demonstrated the specific binding of AKA to the stratum corneum of human epidermis and the absence of any staining of the granular keratinocytes. This binding was confirmed and the AKA antigen precisely localized in human epidermis by immunoelectron microscopy. The antigen was found to be restricted to the filaggrin-containing intracellular fibrous matrix of the corneocytes, up to the desquamating cells. In contrast, MoAbs directed to human filaggrin and to profilaggrin, its precursor, not only stained the intracellular matrix of the lower corneocytes but also the keratohyalin granules of the granular cells, where profilaggrin is stored. These results reinforced by the absence of immunoblotting reactivity of RA sera to profilaggrin suggest that the epitopes recognized by AKA are absent from profilaggrin. Their identification may provide more insight into the pathogenesis of RA.
7912285 Therapeutic effect of intradermal injections with difucosyl lactosamine (dimeric Lex) on p 1993 Dec As reported by us, a new myeloid cell population with an oncofetal membrane marker, dimeric Lex (di-Lex; III3FucV3 FucnLc6), was found in the epiphyseal bone marrow adjacent to the involved joints of patients with severe rheumatoid arthritis (RA). Patients with RA received intradermal (id) injections of di-Lex incorporated in liposome or of high molecular weight glycoprotein, or tumor associated carbohydrate antigen (TCA), containing the same carbohydrate epitope as di-Lex. The epiphyseal myeloid cells were reduced or sometimes eliminated during id injection. In random trials of id injection, observation under clinical and laboratory conditions showed improvement in 63% (17/27) of the patients treated for 6 months with appropriate doses of di-Lex (III3FucnLc4), and in 72% (31/43) of those treated with an identical protocol for TCA. However, id injection with monomeric Lex had no effect.
8154933 Abnormal haem biosynthesis in the chronic anaemia of rheumatoid arthritis. 1994 Mar OBJECTIVES: The chronic microcytic anaemia of rheumatoid arthritis (RA) occurs despite the presence of adequate reticulo-endothelial iron stores. The red cell microcytosis is evidence of impaired haemoglobin production. This study has examined possible abnormalities of erythroid haem biosynthesis that may contribute to the anaemia. METHODS: 5-Aminolaevulinate (ALA) synthase and ferrochelatase activities were assayed in whole bone marrow and in purified erythroblasts from patients with RA and in control subjects. All patients were iron replete with demonstrable iron in the bone marrow. RESULTS: ALA synthase activity was significantly reduced in both whole bone marrow and purified erythroblasts from patients with the anaemia of RA. Erythrocyte protoporphyrin levels were raised in nine of 12 patients tested while ferrochelatase activity was normal. CONCLUSION: These abnormalities provide absolute evidence of abnormal erythroblast haem biosynthesis and iron metabolism in the anaemia of RA and most likely reflect decreased ALA synthase mRNA translation and some abnormality of erythroblast iron transport. Further studies using highly purified erythroblast populations will attempt to identify the causal factors leading to this abnormal erythroblast metabolism.
8507223 Association of HLA-DR4-Dw15 (DRB1*0405) and DR10 with rheumatoid arthritis in a Spanish po 1993 Jun OBJECTIVE: To analyze the associations of HLA class II antigens with rheumatoid arthritis (RA) in a Spanish population. METHODS: We used DNA oligotyping to determine DR types, DQA1 and DQB1 alleles, and DR4 variants in 70 unrelated seropositive RA patients and 189 healthy controls living in Spain. RESULTS: A significantly higher frequency of DR4 was seen in RA patients compared with controls (relative risk [RR] = 2.40). The DR10 specificity correlated most strongly with disease susceptibility (RR = 3.84). A significant decrease in the frequency of DR7 was observed in the RA patients (RR = 0.48). DR4-Dw15 (DRB1*0405) was found to be the unique DR4 allele associated with RA (RR = 4.27, P < 0.05), whereas Dw4 (DRB1*0401) and Dw14 (DRB1*0404/0408) showed no association, and both Dw10 (DRB1*0402) and Dw13 (DRB1*0403/0407) were negative risk factors for the disease. Approximately one-third of the cases of RA could not be explained by the "shared epitope" hypothesis. Investigation of the DQ alleles associated with DR4 showed that the haplotype Dw15-DQ8 (DRB1*0405-DQB1*0302) was a susceptibility factor for RA (RR = 6.36, P < 0.05). CONCLUSION: Our results suggest that HLA class II alleles involved in RA susceptibility can vary among different Caucasian populations.
8463598 Ulnar translation of the carpus in rheumatoid arthritis: an analysis of five determination 1993 Mar Five x-ray methods of assessing ulnar translation of the carpus were compared to each other. Overall, we found the uncompensated semiquantitative method proposed by Gilula et al. to be the most practical and the best method with a sensitivity index of 82%, a specificity index of 88%, an accuracy of 87%, and an interobserver correlation of 90%. The method, however, decreased in specificity and accuracy when a corrective formula was applied to adjust the ulnometacarpal angle to zero degrees deviation. Our conclusion is that the sensitivity indices are relatively low for all methods, and underdiagnosis may occur. At present the semiquantitated method of Gilula et al. is the most practical, with the highest sensitivity index, and is recommended as a screening tool for assessment of ulnar translation of the carpus.
8252984 Circulating immune complexes with pulmonary hemorrhage during pregnancy in idiopathic pulm 1993 Dec Circulating immune complexes occurred during pulmonary hemorrhage in a pregnant patient with idiopathic pulmonary hemosiderosis, an association not previously reported. The patient required mechanical ventilation, but recovered; after a prolonged hospitalization, she was delivered of a healthy infant without further complications.
8388274 A patient with rheumatoid arthritis complicated by Sjögren's syndrome that was possibly c 1993 Jan A 24-year-old woman developed rheumatoid arthritis in 1986. Anti-SS-A antibody was negative, and Sjögren's syndrome was not associated with the disease. In July 1988 the patient developed pyrexia and cervical lymph node swelling. Infectious mononucleosis was suspected, and a previous contact with Epstein-Barr virus (EBV) was indicated. Pyrexia and cervical lymph node swelling occurred repeatedly and after this dry eyes and mouth also developed. In May 1990 the patient again developed pyrexia and cervical lymph node swelling, and she also had anti-SS-A antibodies (64x) and symptoms associated with Sjögren's syndrome. EBV antibody showed reactivation of EBV by the presence of viral capsid antigen-IgM antibody and a decrease in antibody titer against EBV-associated nuclear antigen. The clinical symptoms of repeated fever and cervical lymph node swelling, as well as the reactivation of EBV, suggest that EBV might have been a factor participated in the onset of Sjögren's syndrome in this patient.
7838446 Imaging rheumatic joint diseases with anti-T lymphocyte antibody OKT-3. 1994 Oct T lymphocytes play an important role in the pathogenesis of rheumatoid arthritis (RA). Murine monoclonal antibody OKT-3 (IgG2a), known to be specific for T lymphocyte 20 kD glycoprotein CD3 receptor was labelled with 5 mCi 99Tcm and given intravenously (i.v.) to seven RA and two psoriatic arthritis patients following informed consent to identify inflamed synovium. Anterior and posterior whole body scans and specific regional imaging was commenced 20 min later. At 1 h, approximately 20% of 99Tcm was associated with the lymphocytes. In these patients, all 41 asymptomatic joints and 43 joints with mild pain or minimal tenderness had normal scans. All 34 joints with moderate to severe pain had moderate to marked uptake of radioactivity. Two patients experienced shaking chills for 20-30 min within an hour of 99Tcm-OKT-3 infusion. These results suggest that 99Tcm-OKT-3 imaging serves as an objective surrogate for joint inflammation and could be useful as a measurement of therapeutic effectiveness in RA and other diseases with inflamed synovium. The side effect profile may limit the utility of 99Tcm-OKT-3 but other forms of antibodies directed toward lymphocyte subsets may be useful.
8038273 Influence of electromagnetic fields on the enzyme activity of rheumatoid synovial fluid ce 1994 Apr Since positive clinical effects have been observed in the treatment of rheumatoid arthritis with electromagnetic fields of weak strength and low frequency range (magnetic field strength: 70 microT; frequency: 1.36-14.44 Hz), an attempt was made to analyse the effects of these electromagnetic fields on enzyme activity in monolayer cultures of rheumatoid synovial fluid cells after single irradiation of the cultures for 24 hours. We only investigated the matrix metalloproteinases (collagenase, gelatinase, proteinase 24.11 and aminopeptidases). It was found that electromagnetic fields of such a weak strength and low frequency range do not generally have a uniform effect on the activity of the different proteinases in vitro. While aminopeptidases do not show any great changes in activity, the peptidases hydrolysing N(2,4)-dinitrophenyl-peptide exhibit a distinct increase in activity in the late phase in culture medium without fetal calf serum. In the presence of fetal calf serum this effect is not observed and enzyme activity is diminished. Our experiments do not show whether such a phase-bound increase in the activity of proteinases in vitro is only one finding in a much broader range of effects of electromagnetic fields, or whether it is a specific effect of weak pulsed magnetic fields of 285 +/- 33 nT on enzyme activity after single irradiation. This question requires further elucidation.
8535650 Adverse events in methotrexate-treated rheumatoid arthritis patients. 1995 Nov Methotrexate (MTX) is an antifolate that has been in use for the treatment of rheumatoid arthritis (RA) since the early 1980s. Its efficacy has been clearly documented [1-4] and its administration early in the course of the disease is now generally accepted [5]. Side-effects from low weekly pulse MTX have been reported [1-6] and it was our initial experience that toxicity, rather than lack of efficacy, was the major factor limiting its clinical use [7]. However, when compared with other disease-modifying antirheumatic drugs, its toxicity appears to be comparable to that of antimalarials [8, 9]. The purpose of this paper is to discuss the possible mechanisms responsible for toxicity due to MTX used at low weekly pulse doses for the treatment of RA, as well as the different toxic manifestations reported in the literature.
8853226 An immunohistochemical and immunoelectron microscopic study of adhesion molecules in synov 1996 To investigate the mechanism of synovial pannus formation in rheumatoid arthritis, immunohistochemical and immunoelectron microscopic studies with monoclonal antibodies against the adhesion molecules, CD54 (ICAM-1), CD11a (LFA-1), CDw49a (VLA-1), CDw49b (VLA-2), CDw49c (VLA-3), Cdw49d (VLA-4) and CDw49e (VLA-5), were carried out to determine the pattern of distribution of these molecules at the rheumatoid synovial cartilage junction. Treatment with anti-ICAM-1 resulted in membrane staining of most of the macrophages and fibroblasts infiltrating the synovial tissue and bordering and pannus-cartilage junction, suggesting the possibility that ICAM-1 may function to facilitate the adhesion of synovial type A cells bearing ICAM-1 to type B cells of the pannus. ICAM-1 positive macrophages and fibroblasts were often found to be in contact with lymphoid cells, suggesting also that a cellular immune reaction occurs in the formation of the pannus. In addition, VLA-3, VLA-4 and, particularly, VLA-5 were the predominant beta 1 integrins expressed by rheumatoid synovial pannus. Sine these three integrins all function as fibronectin receptors, it is possible that the fibronectin-rich environment of the rheumatoid cartilage surface effectively traps pannus cells expressing high levels of these molecules. The VLA-5 molecule was found in a pericellular and interterritorial matrix distribution in the present study, strongly suggesting that a receptor-ligand interaction between VLA-5 and cartilage matrix may occur at the early stage of pannus formation. Furthermore, an increase in beta 1 integrin may be necessary for the growth of the pannus and also for the upregulation of the VLA molecules, leading secondarily to increased attachment.
8970036 Expression of heat shock protein on lymphocytes in peripheral blood and synovial fluid fro 1996 Dec OBJECTIVE: To determine whether heat shock proteins (HSP) are expressed on the surface of peripheral blood (PB) lymphocytes and synovial fluid (SF) lymphocytes from patients with rheumatoid arthritis (RA). METHODS: Immunoprecipitation and flow cytometric analyses using anti-Yersinia enterocolitica HSP60 monoclonal antibodies (Mab) were performed. Phenotypes of surface HSP-positive lymphocytes were analyzed further by 2 color flow cytometry. RESULTS: Anti-Y. enterocolitica HSP60 Mab immunoprecipitated 120, 97, 70, 60, 55, and 50 kDa proteins in extracts of healthy donor PB lymphocytes and of Daudi cells after thermal shock. Among these proteins, the 60 kDa HSP showed the greatest degree of precipitation. Surface HSP-positive lymphocytes were detected in 2 of 16 PB and 1 of 12 SF lymphocyte samples. Longitudinal studies indicated that HSP were expressed on the surface of lymphocytes in the active stage, but not in the improvement stage of the disease. Surface HSP-positive lymphocytes were mainly either [gamma delta +] T cells or [CD19+] B cells. CONCLUSION: HSP were expressed on the surface of PB and SF lymphocytes from patients with RA. Surface HSP-positive lymphocytes might be recognized by lymphocytes since HSP are strongly immunogenic.
7570208 [Prognosis and outcome of rheumatoid arthritis--10 to 16 years of anti-rheumatic therapy]. 1995 Jun One hundred twenty-eight rheumatoid arthritis (RA) patients were followed up over a long period of time (mean, 13.3 years; range, 10-16 years) in order to determine the role of pharmacotherapy in RA. Patients were aged 48.2 years on the average (23-79 years) and the mean RA duration was 7.8 years (0-58 years) upon initial visit to this unit. Although pharmacotherapy was effective in improving Lansbury's activity index and ESR, articular bone and cartilage destruction and functional impairment progressed gradually, resulting in the need for total hip, knee or ankle arthroplasty in 46 (96 joints) of the 128 patients. This finding indicates that current pharmacotherapy for RA has limitations in that it cannot completely prevent joint destruction and resulting functional impairment. This suggests that new therapeutic modalities, including new drugs, are necessary. Efforts were also made to determine factors which affect the prognosis of RA. The prognosis seemed pessimistic in RA patients with high activity and rheumatoid factor (RAPA) levels, long duration of illness, high Larsen scores and advanced functional impairment at the time of initial active therapy. It appeared necessary to maintain Lansbury's activity index at 30% or below in order to obtain a good prognosis.
8205399 Effect of exogenous erythropoietin on haem synthesis in anaemic patients with rheumatoid a 1994 Jun The effect of recombinant human erythropoietin (rHuEPO) on haem biosynthesis in peripheral red blood cells was evaluated in 12 patients with RA and anaemia (mean haemoglobin concentration 102 g/l, range 90-109 g/l). Before treatment, the serum concentrations of erythropoietin (EPO) were low (mean 13 pmol/l, range 5-32 pmol/l), the activities of haem-synthesizing enzymes within the reference intervals and the erythrocyte protoporphyrin (E-PROTO) concentrations clearly higher than normal. Nine patients responded with an increase in the haemoglobin level of 15 g/l or more. rHuEPO induced a rise in the mean haem synthase (HAEM-S) activity from a baseline of 12.1 to a maximum of 26.8 pmol/h per 10(6) reticulocytes after 20 weeks of treatment (P < 0.002). The mean E-PROTO concentration also rose and reached its maximum at 8 weeks of treatment. We conclude that correction of anaemia in patients with RA using rHuEPO is associated with an activation of HAEM-S, commonly regarded as the rate-limiting enzyme of haem synthesis in erythroid cells. Functional iron deficiency probably explains the simultaneous rise in E-PROTO concentration.
8224809 Epistatic modeling in rheumatoid arthritis: an application of the Risch theory. 1993 Rheumatoid arthritis (RA) is a disease of unknown etiology but with a presumed complex pattern of inheritance. Risch [Am J Hum Genet 46:222-228, 1990] has shown that the recurrence risk ratio, lambda R, (which is defined as the risk to type R relatives vs. the population prevalence) can be used to evaluate patterns of inheritance in genetically complex diseases. We have used the Risch theory to examine some multiple locus models of inheritance in RA. Recurrence risk ratios in MZ twins and in 1st, 2nd, and 3rd degree relatives are summarized from the literature. The limited data available supports at least a two-locus model of inheritance for RA (assuming that one locus is HLA). Better estimates of the recurrence risk ratios in RA families are required so that the Risch theory can be pursued further.
7738959 Leukoencephalopathy in a patient taking low dose oral methotrexate therapy for rheumatoid 1995 Feb We describe the case of a man who developed a dementing illness with leukoencephalopathy while receiving low dose weekly oral methotrexate (MTX) therapy for rheumatoid arthritis. The white matter changes seen on magnetic resonance imaging and computerized tomogram scan were the same as those seen in cases of leukoencephalopathy that have been reported in patients receiving intravenous or intrathecal methotrexate. Extensive investigation excluded other known causes of white matter disease. Although no improvement either subjectively or objectively occurred in his mental status after cessation of treatment with MTX, he has remained stable. We believe that this may represent a case of oral MTX induced leukoencephalopathy, which has not previously been reported.
8120333 Hydroxychloroquine and chloroquine: assessing the risk of retinal toxicity. 1993 Nov BACKGROUND: During the past 10 years there has been an increase in the use of the antimalarial agents, chloroquine and hydroxychloroquine, in the treatment of various rheumatic diseases. METHODS: In the United States, hydroxychloroquine (Plaquenil) is one of the most commonly prescribed medications for mild to moderately severe rheumatoid arthritis. Both chloroquine and hydroxychloroquine have the potential to produce an irreversible maculopathy. However, this maculopathy occurs almost exclusively at higher than recommended doses. RESULTS: Careful dose monitoring by the rheumatologist, combined with appropriate ocular examination by the eye care professional, can significantly reduce the risk of retinopathy. CONCLUSIONS: This paper discusses the use of chloroquine and hydroxychloroquine in the treatment of rheumatoid arthritis and systemic lupus erythematosus, it summarizes their retinotoxic risk, and it outlines the diagnostic techniques used to evaluate patients treated with these medications.
8485860 Rheumatoid factors. 1993 Apr Rheumatoid factors (RFs) have been studied for over 50 years and are probably the most written about of any antibody. Nevertheless, the etiology of these RFs and the precise role they play in the pathogenesis of rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) remain a major interest. When RFs participate in the generation of inflammation in RA and JRA, they probably do so by forming immune complexes (IC) or are themselves able to bring about the inflammatory response. Their presence has been associated with more severe disease, vasculitis, and systemic symptoms. The present review summarises the literature over the last few years on new and interesting findings on RF. This review covers an update on RF assays, RF cross-reactivity, specificity studies, immune complex formation, RF lymphocyte studies, and RF binding.