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ID PMID Title PublicationDate abstract
1597009 Urinary glycosaminoglycan excretion in rheumatic diseases. 1992 Jun We used Alcian Blue (AB) and dimethylmethylene blue (DMB) methods to measure glycosaminoglycan (GAG) excretion in the first morning urine specimens of patients with osteoarthritis (OA), ankylosing spondylitis (AS), and rheumatoid arthritis (RA) in different stages of disease. By the AB method, urinary GAG excretion in patients with RA was not different from healthy control subjects. However, the DMB method showed significant differences (in milligrams of GAG per gram of creatinine) for OA (median 25.4, range 14.3-44.0, P less than 0.01, n = 23) and RA patients (median 33.0; range 10.0-147.6; P less than 0.001, n = 63) in comparison with unaffected individuals (median 20.2; range 8.9-41.4, n = 38). We noted a significant difference in urinary GAG excretion between RA and OA patients (P less than 0.01) and between RA and AS (P less than 0.01) patients. The DMB method was further investigated by clinical decision analysis. The DMB method is simple and rapid and may be useful in diagnosing RA by distinguishing between RA and OA or AS.
8447692 Responses of synovial fluid and peripheral blood mononuclear cells to bacterial antigens a 1993 Feb The specificity of T cells in the inflamed joints of patients with rheumatoid arthritis (RA) has been the subject of much study. Bacterial antigens are suspect in the aetiology of rheumatic diseases. The responsiveness of the mononuclear cell fraction of peripheral blood and synovial fluid of patients with RA and of patients with rheumatic diseases other than RA to bacterial antigens such as cell wall fragments of the anaerobic intestinal flora, cell wall fragments of Streptococcus pyogenes, intestinal flora derived peptidoglycan polysaccharide complexes, the 65 kilodalton protein of Mycobacterium tuberculosis, and muramyldipeptide was investigated. No significant difference in response was found to all these bacterial antigens in the synovial fluid of patients with RA compared with the responses in patients with other rheumatic diseases. The highest responsiveness in the synovial fluid of the patients with RA was to the streptococcal cell wall fragments and to the 65 kilodalton protein. Higher responses to several bacterial antigens in the synovial fluid of patients with RA were found compared with peripheral blood from the same patient group. The antigen presenting cell population of the synovial fluid in patients with RA and the patients with other rheumatic diseases was found to be stimulatory for autologous peripheral blood T cells even in the absence of antigen. This suggests an important role for the synovial antigen presenting cell in the aetiology of inflammatory joint diseases.
7794038 Identification and functional importance of plasma kallikrein in the synovial fluids of pa 1995 May OBJECTIVES: To determine and identify, unequivocally, if plasma kallikrein (PK) is present in the synovial fluid of patients with rheumatoid (RA), psoriatic (PA) and osteo (OA) arthritis, and to consider its functional importance in the inflamed joint. METHODS: Therapeutically aspirated synovial fluids (pooled and individual samples, n = 66) were obtained from patients with arthritis. In addition, serum (n = 14) was collected from RA patients, and saliva (n = 10) and urine (n = 10) from normal individuals. Enzymic (amidase) and immunoreactive activities of PK and its precursor, prokallikrein (PPK), were determined. The presence of PK was assessed by incubation with soya bean trypsin inhibitor (SBTI), and by adsorption with anti-PK antibody linked to Sepharose. An enzyme-linked immunosorbant assay (ELISA) for PK was developed for quantitative measurement of total PK in biological fluids. Enhancement of the PK dose-response by RA synovial fluid made it necessary to remove RF from synovial fluids before determination of PK by ELISA. RESULTS: Amidase activity was demonstrated in synovial fluid pools and shown to be inhibited completely by SBTI, and removed by prior treatment with anti-PK Sepharose. Total PK activity (PK + PPK) from individual synovial fluid specimens did not differ significantly between patients with RA (median activity 76 mU/g protein), PA (80 mU/g protein) or OA (60 mU/g protein). Similar results were obtained when active PK alone was measured. No correlation was found between active PK or total PK values and the severity score for individual joints. Most of the measured immunoreactivity was removed by adsorption with anti-PK antibody linked to Sepharose. CONCLUSION: The results support the hypothesis that plasma kallikrein is present in synovial fluid. The enzyme may be important in the pathogenesis of inflamed joints.
8743663 Increase of immunologically relevant parameters in correlation with Baker classification i 1996 May A variety of studies have suggested a possible immune reaction to silicone implants, although an increased frequency of rheumatic disorders among implant recipients could not be established. Several immunologically relevant humoral parameters were investigated in 239 breast implant recipients. The following parameters were determined: immunoglobulin G and M, complement C3 and C4, rheumatoid factor, C-reactive protein, antinuclear antibodies, antimitochondrial antibodies, and antithyroglobulin and antimicrosomal antibodies of the thyroid gland. Levels of complement C3 were elevated in 42.5% of the patients. No difference could be observed between silicone gel-filled and saline-filled implant recipients. Complement C4 was increased in 21.3% of the patients and a parallel relationship was observed between elevated C4 and C3 levels (p < 0.0015). In 28% of the patients, the antithyroglobulin titer was elevated > 200 U/ml. No difference was found between silicone gel-filled and saline-filled implant recipients. Elevation of antimicrosomal antibodies existed in 14.3% of the patients and was correlated significantly with antithyroglobulin antibodies (p < 0.0347). In accordance with the classification developed by Baker, we observed a significant correlation between capsule fibrosis types Baker I and II, and elevated C3 values (p < 0.0004) in silicone gel-filled but not in saline-filled implant recipients. Additionally, a correlation was found between increased antithyroglobulin titers (< 200 U/ml) and capsule fibrosis types Baker I and II (p < 0.0001) in this group. In the study presented here, an increase of several humoral parameters could be demonstrated in breast implant recipients, although we failed to correlate these findings with any clinical symptoms.
8230008 Aspirin is not associated with more toxicity than other nonsteroidal antiinflammatory drug 1993 Aug OBJECTIVE: To compare the clinical and laboratory toxicities of aspirin vs nonsteroidal antiinflammatory drugs (NSAID) in combination with low dose methotrexate (MTX). METHODS: We retrospectively examined 34 patients with rheumatoid arthritis (RA) who completed 12 months of a prospective MTX trial. Analysis included descriptive and logistic regression. RESULTS: Twelve patients took an average of 4.5 g aspirin daily; 22 patients took other NSAID at stable doses. Limiting toxicity was not different between aspirin and NSAID treatment groups, respectively, for stomatitis (33 vs 27%), gastrointestinal symptoms (25 vs 18%), hepatic (25 vs 27%), or other toxicity. However, using logistic regression procedures, weight adjusted weekly MTX dose and prednisone dose correlated with toxicity. CONCLUSION: While toxicity is common when aspirin or NSAID are used with MTX to treat RA, there is no clinical difference between aspirin and NSAID with respect to that toxicity during 12 months of therapy.
7533683 Identification and characterization of a tolerogenic T cell determinant within residues 18 1995 Apr The murine model of collagen-induced arthritis is characterized by the development of an immune response against joint cartilage. Arthritis can be significantly suppressed by the administration of type II collagen (CII) or one of the CNBr peptides, CB11 (CII 124-402) as a tolerogen prior to immunization. We have previously shown that two synthetic peptides, representing sequences CII 260-270 and CII 181-209, are effective tolerogens. In this paper, we now characterize the T cell determinant with CII 181-209. A series of synthetic peptides overlapping CII 181-209 and analogs of chick CII 181-209 containing site-directed amino acid substitutions was developed and cultured with T cells from DBA/1 mice immunized with CII. Supernatants were collected and analyzed for the presence of the T cell lymphokine IFN-gamma. These data indicate the critical T cell determinant to be located within CII 190-200. This conclusion is further supported by the observation that an unodecapeptide representing CII 190-200 was just as effective as CII 181-209 in suppressing arthritis and anti-CII antibody response when tested as a tolerogen. Analogs containing single amino acid substitutions at residues 191, 194, 197, 198, or 200 were significantly less effective in inducing T cell responses. Each of these peptide analogs was then given as neonatal tolerogens to DBA/1 mice. Mice were subsequently immunized and observed for the development of arthritis. These studies identified residues 194, 197, 198, and 200, and probably residue 191, as critical for tolerance and the suppression of arthritis. Elucidation of the fine structures of T cell determinants which are critical for suppression of arthritis should allow these techniques to be used for developing specific immunotherapeutic approaches to autoimmune arthritis.
7798107 Joint motion of bipolar femoral prostheses. 1995 Apr From 1982 to 1992, 251 bipolar hip arthroplasties were performed on 213 patients. Among them, 117 bipolar femoral prostheses were randomly selected to examine the behavior of abduction motion under weight-bearing loads. Roentgenographic motion study was performed at an average of 46.5 months after surgery (range, 2-110 months). One hundred one prostheses used in dysplastic osteoarthritic, rheumatoid, and revised failed total hip arthroplasty patients moved 18.2% at the outer bearing and 81.8% at the inner bearing, while 16 prostheses used in femoral neck fracture and osteonecrosis of the femoral head patients moved 49.7% at the inner bearing and 50.3% at the outer bearing. There was a statistical difference in the motion pattern between the two groups. The abduction motion behavior of the bipolar femoral prostheses was not affected by the length of the follow-up period, the diameter of the outer heads, or the position of the prostheses on immediate postoperative roentgenograms.
8099458 Type X collagen expression in osteoarthritic and rheumatoid articular cartilage. 1993 Type X collagen is a short chain, non-fibril-forming collagen synthesized primarily by hypertrophic chondrocytes in the growth plate of fetal cartilage. Previously, we have also identified type X collagen in the extracellular matrix of fibrillated, osteoarthritic but not in normal articular cartilage using biochemical and immunohistochemical techniques (von der Mark et al. 1992a). Here we compare the expression of type X with types I and II collagen in normal and degenerate human articular cartilage by in situ hybridization. Signals for cytoplasmic alpha 1(X) collagen mRNA were not detectable in sections of healthy adult articular cartilage, but few specimens of osteoarthritic articular cartilage showed moderate expression of type X collagen in deep zones, but not in the upper fibrillated zone where type X collagen was detected by immunofluorescence. This apparent discrepancy may be explained by the relatively short phases of type X collagen gene activity in osteoarthritis and the short mRNA half-life compared with the longer half-life of the type X collagen protein. At sites of newly formed osteophytic and repair cartilage, alpha 1(X) mRNA was strongly expressed in hypertrophic cells, marking the areas of endochondral bone formation. As in hypertrophic chondrocytes in the proliferative zone of fetal cartilage, type X collagen expression was also associated with strong type II collagen expression.
7504827 CD5-positive and CD5-negative rheumatoid factor-secreting B cells in IgA nephropathy, rheu 1993 Dec The relative contributions of CD5+ and CD5- B-cells in production of rheumatoid factors (RF) was evaluated in polyclonally activated B-cells from patients with IgA nephropathy (IgAN), rheumatoid arthritis (RA) and Graves' disease (GD). In IgAN and RA, diseases in which RFs are believed to be involved in pathogenesis, there were 10- and 4-fold decreases respectively in CD5+ IgG-RF-secreting B-cells compared with controls. Furthermore, the number of CD5- IgG-RF- and IgA-RF-secreting B-cells were increased 12- and 14-fold in IgAN and 9- and 4-fold in RA. Such abnormalities were not apparent in GD, in which RFs have not been implicated in pathogenesis. These findings are compatible with the concept of CD5+ RF-secreting B-cells normally acting to prevent production of potentially pathogenic RFs by CD5- B-cells. When IgAN or RA patients' B-cells were activated in the presence of control instead of autologous CD4+ cells, numbers of RF-secreting CD5- B-cells were reduced to the levels seen with control B-cells plus control T-helper cells. Presumably lymphokine secretion profiles of T-helper cells would be important in determining whether CD5+ or CD5- B-cells are activated to secrete RFs, and perhaps therapeutic manipulation of these profiles could restore normal activity of CD5+ B-cells in IgAN and RA.
7882554 Expression of endogenous retroviruses, ERV3 and lambda 4-1, in synovial tissues from patie 1995 Mar We addressed the question of whether or not expression of human endogenous retroviruses (ERV), ERV3 and lambda 4-1, is related to the pathogenesis of rheumatoid arthritis (RA). In genomic Southern hybridization, there were no significant differences between RA patients and healthy volunteers with regard to frequencies of restriction fragment length polymorphism (RFLP) patterns, for either ERV3 or lambda 4-1. By Northern blot analysis using fresh synovial tissues, cultured synovial cells, and peripheral blood mononuclear cells (PBMC) from patients with RA, we noted two molecular species of ERV3 mRNAs of 3.5 kb and 9.0 kb sizes, and one single molecular species of lambda 4-1 mRNAs of 4.2 kb size. The expression was detected not only in RA patients but also in synovial cells from osteoarthritis (OA) as a non-RA control and PBMC from healthy volunteers, and was not related to RA activities or treatments. Although ERV3 and lambda 4-1 expression may not be directly associated with the pathogenic pathway of RA, the possibility exists that human ERV may have a causative role in autoimmune diseases, including RA. We also examined the effect of cytokines on the transcriptional regulation of ERV3. Although the level of ERV3 expression in cultured synovial cells did not change with IL-1 beta treatment, the level for cultured proximal tubular epithelial cells (hKEC) was up-regulated.
8863160 Linkage of rheumatoid arthritis to the candidate gene NRAMP1 on 2q35. 1996 Aug The macrophage resistance gene NRAMP1 regulates priming/activation of macrophages for enhanced TNF alpha, IL 1 beta, and MHC class II expression. Since all of these functions are of potential importance in the induction or maintenance or both of autoimmune disease, samples from the Arthritis and Rheumatism Council's repository of multicase rheumatoid arthritis families were typed for a dinucleotide repeat in the NRAMP1 promoter region and four other 2q34 (TNP1) or 2q35 (IL8R, VIL1, DES) marker genes. Identity by descent (IBD) sib pair analysis using a three locus haplotype NRAMP1-IL8RB-VIL1, or NRAMP1 alone, provided preliminary evidence (maximum lod score = 1.01, p = 0.024) for a gene in this region contributing to suceptibility to rheumatoid arthritis. Candidacy for NRAMP1 as the disease susceptibility gene was supported by a significant bias (p = 0.048) towards transmission of the NRAMP1 promoter region allele 3 in affected offspring.
7955556 The T cell repertoire against cryptic self determinants and its involvement in autoimmunit 1994 Dec Developing T cells potentially directed against cryptic self determinants escape tolerance induction in the thymus and thereby enrich the T cell repertoire. Cryptic self peptides become expressed at inflammatory tissue sites which can lead to engagement of this repertoire, leading to induction and/or perpetuation of autoimmune reactivity. On the other hand, expression of cryptic self determinants on tumor cells can be useful in generating effective anti-tumor immunity. This self-directed T cell repertoire can also be activated silently to induce memory and participate unexpectedly in responses to foreign antigens and is responsible for molecular mimicry. Finally, peptides containing cryptic determinants can be utilized for peptide-based immunotherapy.
8700841 Immune response of HLA-DQ8 transgenic mice to peptides from the third hypervariable region 1996 Mar 5 The major histocompatibility complex class II genes play an important role in the genetic predisposition to many autoimmune diseases. In the case of rheumatoid arthritis (RA), the human leukocyte antigen (HLA)-DRB1 locus has been implicated in the disease predisposition. The "shared epitope" hypothesis predicts that similar motifs within the third hypervariable (HV3) regions of some HLA-DRB1 alleles are responsible for the class II-associated predisposition to RA. Using a line of transgenic mice expressing the DQB1*0302/DQA1*0301 (DQ8) genes in the absence of endogenous mouse class II molecules, we have analyzed the antigenicity of peptides covering the HV3 regions of RA-associated and nonassociated DRB1 molecules. Our results show that a correlation exists between proliferative response to peptides derived from the HV3 regions of DRB1 chains and nonassociation of the corresponding alleles with RA predisposition. While HV3 peptides derived from nonassociated DRB1 molecules are highly immunogenic in DQ8 transgenic mice, all the HV3 peptides derived from RA-associated DRB1 alleles fail to induce a DQ8-restricted T-cell response. These data suggest that the role of the "shared epitope" in RA predisposition may be through the shaping of the T-cell repertoire.
8166649 Structural analysis of the N-glycans from human immunoglobulin A1: comparison of normal hu 1994 Apr 1 The primary structures of the N-linked oligosaccharides from normal human serum IgA1 were determined by a combination of sequential exoglycosidase digestion, Bio-Gel P-4 chromatography, anion-exchange chromatography and one-dimensional n.m.r. spectroscopy. Three major N-linked disialylated biantennary-complex-type structures were found (55%). The remaining N-linked oligosaccharides consisted of at least nine further structures, some of which (7%) were of the triantennary type and included disialylated triantennary oligosaccharides with outer-arm fucose substitution [Fuc alpha 1-3(4)]. Compared with IgG, the N-glycan structures on IgA are more completely processed: the outer arms have a higher proportion of galactose and sialic acid, and only trace levels of incompletely galactosylated oligosaccharides, commonly found on IgG, were detected. Analysis of the sialylated O-glycans revealed that 64% were [NeuAc2 alpha 3(6)]2Gal beta 3GalNAc and 9% were [NeuAc2 alpha 3(6)]-Gal beta 4GlcNAc beta 6[NeuAc2 alpha 3(6)Gal beta 3]GalNAc, and 27% were monosialylated. The N-linked glycosylation of both serum IgA1 and IgG isolated from a group of six normal individuals was compared with that from ten patients with rheumatoid arthritis (RA). In contrast with the hypogalactosylation found in IgG from diseased sera, there was no evidence of an equivalent decrease in the galactosylation of the IgA1 oligosaccharides. In addition, the N-glycosylation of IgA1 was remarkably consistent within the group of normal individuals. These data suggest that incomplete galactosylation of N-linked glycans and its augmentation in RA does not extend to IgA1 and that the RA-associated galactosyltransferase deficiency may be restricted to cells producing gamma-chain.
7905877 Characterization of the plasminogen receptors of normal and rheumatoid arthritis human syn 1994 Feb 11 Plasminogen (Pg) activation on the surface of rheumatoid arthritis (RA) synovial fibroblasts by the urinary-type Pg activator induced a significant increase in cytosolic free Ca2+ concentration. This response was not observed in normal synovial fibroblasts, suggesting different Pg binding and activation mechanisms in these cell types. Pg receptors from both cell types were isolated by affinity chromatography using Pg covalently bound to Sepharose 4B. RA synovial fibroblasts express a Pg receptor complex composed of a glycoprotein IIb/IIIa-related protein in association with a 130-kDa protein that is antigenically related to the alpha 2-macroglobulin receptor-associated protein and dipeptidyl peptidase IV. This receptor complex appears to bind to both Pg and fibronectin. The Pg "receptor" in normal synovial fibroblasts is composed of a 97-kDa protein also antigenically related to the alpha 2-macroglobulin receptor-associated protein. Both cell types express the urinary-type Pg activator receptor on their surfaces. Our results suggest that RA synovial fibroblasts express novel proteins involved in Pg binding, activation, and signal transduction, which are absent in normal synovial fibroblasts.
1430952 Rheumatoid wrists treated with synovectomy of the extensor tendons and the wrist joint com 1992 Nov Forty-three rheumatoid wrists in 43 patients with bilateral wrist involvement were treated with synovectomy of the extensor tendons and wrist joint combined with a Darrach procedure in the period from 1966 to 1986. Clinical and radiologic assessment of the wrists was carried out after an average follow-up period of 11 years, with comparison of the treated and the opposite untreated wrists. The authors confirmed what others have concluded regarding the operation: pain was generally decreased, forearm rotation increased, and wrist extension and palmar flexion changed little. Radiologically, carpal collapse and palmar carpal subluxation progressed nearly parallel to the opposite wrists, but ulnar carpal shift was much greater in the surgically treated wrists. Therefore it is suggested that some measure to prevent ulnar carpal shift, such as Clayton's tendon transfer or radiolunate arthrodesis, should be included in this operation.
7482338 [Antibodies to skeletal muscle myofibrillar proteins in the diagnosis of rheumatoid arthri 1995 One of the mechanisms of muscular involvement in RA patients was elucidated by identification of antibodies to skeletal muscle components (actin and tropomyosin). Clinical symptoms of skeletal muscles involvement in RA proved to be associated with elevated count of tropomyosin antibodies against an insignificant informative value of actin. Enzyme immunoassay with tropomyosin has established a direct correlation between the number of the antibodies and RA activity.
8252325 D-penicillamine and polymyositis: the significance of the anti-Jo-1 antibody. 1993 Dec A 57-yr-old lady developed polymyositis whilst taking D-penicillamine for RA. D-Penicillamine-induced polymyositis occurs in RA with a greater frequency than idiopathic polymyositis. Anti-acetyl choline receptor antibodies and ANA were positive, consistent with drug-induced disease. Anti-Jo-1 antibodies are considered specific for idiopathic myositis, and their presence was unexpected. Following withdrawal of the drug, the disappearance of the anti-Jo-1 and other antibodies coincident with clinical improvement, suggested that D-penicillamine was responsible for inducing antibody production.
8425367 V-Y quadricepsplasty in total knee arthroplasty. 1993 Jan The results in 14 consecutive patients (16 knees) who have had total knee arthroplasty (TKA) with a V-Y quadricepsplasty were reviewed. There were eight men and six women with an average age of 66.2 years. Nine patients (ten knees) had revision arthroplasty and five patients (six knees) had primary arthroplasty. Nine of the 14 patients were examined and evaluated in the biomechanics laboratory using the modified Cybex-II system at a mean of three years from surgery. Using the knee rating score of the Hospital for Special Surgery, there were two excellent, ten good, two fair, and two poor results. The average active range of motion was 4 degrees to 85 degrees. Biomechanical testing revealed statistically significant weakness in extension compared with the contralateral side only at test speeds of 120, 180, and 240 degrees per second in those patients who had contralateral normal knees. The affected side at other test speeds were weaker but did not reach statistically significant weakness when compared with the contralateral knee. Comparing V-Y quadricepsplasty to normal medial parapatellar TKA patients, the extensor mechanism was weaker in the V-Y group but not to a significant degree. If one requires a V-Y quadricepsplasty during TKA, one can expect near normal active extension and moderate weakness in extension. Knee scores reflect the difficult reconstructive challenges that are inherent in patients who require a V-Y quadricepsplasty.
8873293 Medical comorbidity in schizophrenia. 1996 The extent and consequences of medical comorbidity in patients with schizophrenia are generally underrecognized. Patients with comorbid conditions are usually excluded from research studies, although they probably represent the majority of individuals with schizophrenia. Elderly patients are especially likely to have comorbid disorders. In this article, we review selected literature on medical comorbidity in schizophrenia, including physical illnesses, substance use, cognitive impairment, sensory deficits, and iatrogenic comorbidity. Data from the University of California, San Diego Clinical Research Center on late-life psychosis are also presented. Older schizophrenia patients report fewer comorbid physical illnesses than healthy comparison subjects, but their illnesses tend to be more severe. These results suggest that schizophrenia patients may receive less than adequate health care. Substance abuse is more common in patients with schizophrenia than in the general population and may exacerbate psychiatric symptoms in these patients. Although generalized cognitive impairment is associated with schizophrenia, the main contributors to dementia in older patients are more likely to be comorbid neurological and other physical disorders, substance abuse, and medication side effects. Iatrogenic comorbidity results primarily from the use of neuroleptic (e.g., tardive dyskinesia) and anticholinergic (e.g., confusion) medications. Clinical and research recommendations are made for management of comorbidity in schizophrenia.