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ID PMID Title PublicationDate abstract
8531350 [Isotypes and subtypes of anti-SS-A and/or SS-B antibodies in different subgroups of Sjög 1995 Oct Profiles of anti-SS-A/SS-B antibodies, including their isotypes and subtypes, in patients with primary Sjögren's syndrome (SS) were similar to those in SS patients with systemic lupus erythematosus (SLE), except for anti-SS-A52-Kd/60-Kd antibody profiles. The incidence and titers of these antibodies in SS patients with rheumatoid arthritis, however, were lower than those in primary SS or SS patients with SLE. It is suggested that IgA anti-SS-A/SS-B antibodies are produced in the salivary gland. In addition, IgG1 anti-SS-A antibodies were dominant in all groups of SS patients examined. The results indicate a preferential activation of Th2 helper T cells in SS.
7939136 Interleukin-4 (IL-4) induces down-modulation and shedding of the p55 tumour necrosis facto 1994 Recombinant human interleukin-4 (rhIL-4) and rhIL-1 alpha each produced a rapid down-modulation of tumour necrosis factor receptor (TNFR) on rheumatoid synovial fibroblasts (RSF) in vitro. This was associated with a staurosporine-resistant increase in p55 soluble TNFR levels, in culture media, suggesting that down-modulation was due to enhanced receptor shedding via a protein kinase C-independent mechanism. Pretreatment with rhIL-4 reduced the subsequent tumour necrosis factor alpha (TNF alpha) stimulation of prostaglandin E (PGE) and matrix metalloproteinase-3 (MMP-3) production by RSF. Thus, the potential anti-synovial monokine properties of rhIL-4 are not confined to inhibiting monokine production but also include the ability to interfere with their action on cells that constitute a substantial proportion of the rheumatoid synovium.
7526869 Elevated expression of CD80 (B7/BB1) and other accessory molecules on synovial fluid monon 1994 Nov OBJECTIVE: To assess the expression of important accessory molecules such as CD80 (B7/BB1) and CD54 (intercellular adhesion molecule 1) on potential antigen-presenting cells (APC) in the synovial fluid (SF) of patients with rheumatoid arthritis (RA). METHODS: The level of expression of various accessory molecules on T cells, monocytes, and CD5+ or CD5- B cells from RA SF was compared, by multiparameter flow cytometric analysis, with the expression on peripheral blood (PB) mononuclear cells from the same patients and from normal controls. The functional significance of increased expression of these accessory molecules was assessed by the ability of the different cell populations to stimulate T cells in the mixed lymphocyte reaction. RESULTS: Monocytes, T cells, and B cells isolated from the SF of inflamed joints of patients with RA expressed significantly higher levels of CD80 and CD54 than those from the PB of RA patients or normal controls. CD11b and CD11c expression also were increased on SF B cells, while SF monocytes exhibited enhanced levels of CD40. Further, we found that the elevated CD80 and CD54 levels in RA SF cells may enhance the capacity of these cells to act as stimulatory APC. CONCLUSION: This is the first demonstration that specific cell subsets constitutively express increased levels of CD80 at a site of autoimmune pathology, which could potentially contribute to the initiation or maintenance of autoimmune disease.
9172817 The complement system in chronic lymphocytic leukemia: a possible role in autoimmune manif 1996 May We describe the complement system of three CLL patients who developed autoimmune complications in the course of their disease. The complement profile was pathological in both CLL patients with active autoimmune diseases, while it showed no deficiency in the patient with quiescent autoimmunity. The complement profile could be an early marker for development of autoimmunity in CLL patients
7510905 Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. 1994 Mar 25 Fas is an apoptosis-signaling receptor molecule on the surface of a number of cell types. Molecular cloning and nucleotide sequence analysis revealed a human Fas messenger RNA variant capable of encoding a soluble Fas molecule lacking the transmembrane domain because of the deletion of an exon encoding this region. The expression of soluble Fas was confirmed by flow cytometry and immunocytochemical analysis. Supernatants from cells transfected with the variant messenger RNA blocked apoptosis induced by the antibody to Fas. Levels of soluble Fas were elevated in patients with systemic lupus erythematosus, and mice injected with soluble Fas displayed autoimmune features.
8440076 Human CD4 modulation in vivo induced by antibody treatment. 1993 Jan Clinical improvement after treatment with anti-CD4 antibodies has been documented in patients suffering from rheumatoid arthritis. This observation has stimulated the interest in effects induced by the in vivo application of anti-CD4 antibodies. Here, we have investigated features of CD4 modulation during and after anti-CD4 therapy with the monoclonal anti-body MAX.16H5. Depletion of circulating helper T cells was accompanied by modulation of the CD4 molecule down to 30% of the initial antigen density 1 hr after antibody infusion. However, despite the reappearance of CD4+ cells in the circulation CD4 remained down-modulated for up to 28 days without a significant residual anti-CD4 binding. Depletion of CD4+ cells as well as CD4 modulation were observed to a similar extent both in responders and non-responders to anti-CD4 therapy. Modulation of CD4 was more effective in vivo than in vitro with a mean reduction of CD4 density down to 46% in vitro. It was induced in varying degrees by all anti-CD4 antibodies investigated except for OKT4 and required viable monocytes in the case of MAX.16H5 and most of the anti-CD4 antibodies investigated. Supernatants from LPS-activated monocytes or the addition of monocytes that were freeze-fractioned or fixed monocytes did not substitute for this requirement. The effect was Fc-receptor dependent since F(ab)2 fragments of MAX.16H5 did not induce CD4 modulation. No significant co-modulation was found for a variety of T-cell surface antigens including CD2, CD3, CD8, CD45R, CD45RO, CD25, CDw29, and HLA-DR. In order to test functional effects, the influence of CD4 modulation on the increase of free cytosolic Ca2+ concentration ([Ca2+]i) stimulated via the T-cell receptor complex by an anti-CD3 antibody was studied. A significant inhibition was observed upon direct binding of anti-CD4 to its ligand. However, a diminished CD4 density alone as induced by in vivo modulation did not reduce, but rather enhanced the T cell receptor-mediated mobilization of [Ca2+]i in T cells of the patients. Taken together, no evidence was found that CD4 modulation per se could explain the beneficial effects of anti-CD4 therapy.
7843804 Role of oxygen radicals and IL-6 in IL-1-dependent cartilage matrix degradation. 1994 Dec It has been suggested that IL-1 produces cartilage matrix degradation by metalloproteinases such as collagenase and that such degradation is regulated by metalloproteinase inhibitors. In the present study, the effects of IL-6 and oxygen radical scavengers on cartilage matrix degradation were studied. Superoxide dismutase, catalase, or methionine all significantly inhibited cartilage matrix degradation both in IL-1 beta-stimulated and unstimulated experimental conditions. Both 10 mM EDTA and 100 nM tissue inhibitor of metalloproteinase (TIMP) significantly inhibited cartilage matrix degradation. The addition of methionine significantly inhibited collagenase activity produced in the culture supernatants of chondrocytes stimulated with IL-1 beta. IL-6 significantly suppressed cartilage matrix degradation produced spontaneously or by IL-1 beta stimulation in chondrocytes. IL-6 inhibited superoxide production by chondrocytes both in IL-1 beta-stimulated or unstimulated conditions. These results suggest that oxygen radicals are involved in cartilage matrix degradation mediated by both paracrine and autocrine IL-1 mechanisms and that oxygen radical-mediated activation of collagenase in chondrocytes may explain the mechanisms of how oxygen radicals are involved in cartilage matrix degradation. IL-6 inhibited superoxide production in chondrocytes and thus inhibited cartilage matrix degradation.
7569401 Bronchiolitis obliterans organizing pneumonia. 1995 Jun Bronchiolitis obliterans organizing pneumonia (BOOP) is increasingly recognized as an important cause of diffuse infiltrative lung disease. It is a diagnostic consideration in patients with a febrile flu-like illness of a few weeks' duration and a roentgenogram showing bilateral patchy infiltrates that are not responsive to a typical course of antibiotics. It is defined as granulated tissue plugs within lumens of small airways that extend into alveolar ducts and alveoli. Clinically, a flu-like illness, cough, and crackles are common. Pulmonary function studies of patients show a decreased vital capacity, normal flow rates (except in smokers), and a decreased diffusing capacity. It is generally idiopathic, but it may occur during the resolution of a viral or mycoplasma pneumonia. It is also associated with a variety of systemic illnesses and clinical settings. These include the connective tissue disorders, antineoplastic and other drugs, and immunological disorders, as well as bone marrow and lung transplantation. There are numerous related disorders, including human immunodeficiency virus infection, radiation therapy, thyroiditis, and alcoholic cirrhosis. In idiopathic BOOP, complete resolution occurs in 65% to 85% of patients treated with corticosteroid therapy. This type of therapy is often effective in patients with associated systemic disorders or in other clinical settings, but there may be limited or no response in patients with dermatomyositis, immunosuppression, or interstitial opacities at the lung bases. Respiratory failure leading to death may occur in 5% of patients. It is important to add BOOP to the differential diagnosis of febrile, noninfectious illnesses that are mimics of pneumonia.
8101091 Aminopeptidase N (CD13, EC 3.3.4.11.2) occurs on the surface of resting and concanavalin A 1993 Apr Using different approaches evidence is provided that aminopeptidase N (APN, EC 3.4.11.2, CD13) is expressed on the surface of resting and stimulated human lymphocytes. 1) 50% of total Ala-pNA hydrolysis of viable cells was found to be due to the ectoenzyme APN as revealed by titration with the new inhibitor probestin in comparison to purified APN from human kidney (Ki value 6.5 nM). After stimulation with ConA an increase of Ala-pNA hydrolysis was observed from 8 pkat up to 15 pkat/10(6) cells. 2) This correlated with an increase of APN (CD13) surface expression as detected by antibody surface labeling of unstimulated (5-12% CD13 positive cells) and stimulated lymphocytes (28-36% CD13 positive lymphocytes) using polyclonal and monoclonal antibodies. 3) In vivo APN was found to be expressed on the surface of up to 50% lymphocytes isolated from the synovial fluid of rheumatoid patients.
1487488 Characterization and immunolocalization of RNA polymerase I transcription factor UBF with 1992 Dec We have used anti-NOR serum from a patient with rheumatoid arthritis, to study its reactivity on different phylogenetically separated species such as protozoa, higher plants, birds and mammals. The biochemical characteristics of the antigens detected after applying mono- and two-dimensional electrophoresis and electrophoretic transfers confirm that they correspond to the rRNA polymerase I transcription factor UBF. We have demonstrated the different molecular sizes, depending on the cell complexity, but the same neutral isoelectric points in whole cell extracts of the different species. We have also demonstrated an immunolocalization of this transcription factor to the fibrillar component in all the species studied. These results suggest a high conservation of UBF throughout evolution and the possibility of using this anti-NOR serum as a tool for the study of the structure, nucleolar organization and functional roles of the different nucleolar components.
8243794 Non-steroidal anti-inflammatory drug-induced gastropathy: a comparative endoscopic and his 1993 Mar A 4-week double-blind study compared the potential for 20 mg/day tenoxicam or 100 mg/day diclofenac sodium to induce gastropathy in 36 patients with joint disease and assessed the influence of gastric colonization by Helicobacter pylori. Endoscopic assessment at the end of 4 weeks indicated that the mucosa was normal in 79% of tenoxicam-treated patients and 59% of diclofenac-treated patients. Only 5% of patients in the tenoxicam group developed severe gastroduodenitis (> 11 haemorrhages or erosions) compared with 18% in the diclofenac group. Histological evaluation indicated that 58% and 47%, respectively, of tenoxicam-treated and diclofenac-treated patients retained normal mucosa after treatment. Diclofenac treatment was discontinued in two patients, due to a duodenal ulcer or severe erosive gastritis. Overall, 5/14 patients with moderate to severe colonization with Helicobacter pylori developed severe chronic active gastritis or ulceration, compared with the 1/22 patients in whom colonization was either absent or mild (P = 0.02). Tenoxicam and diclofenac did not show major differences in terms of gastrointestinal safety, although the trends favoured tenoxicam. The presence of severe colonization of the gastric mucosa with Helicobacter pylori appears to be an important factor for development of severe gastritis or ulceration.
8287546 Concanavalin A-bound selenoprotein in human serum analyzed by graphite furnace atomic abso 1994 Jan We developed an assay for the direct determination of selenium in serum with a Perkin-Elmer Model 4100ZL Zeeman atomic absorption spectrometer and Ag-Cu-Mg modifier. We used this assay to analyze concanavalin A-bound selenoprotein (CABSP) in human serum after concanavalin A (ConA) affinity chromatography. The CABSP was identified as a single-chain glycoprotein of 57.3 kDa. Carbohydrate units were N- and O-linked to the protein. The selenium moiety was selenocysteine. Total selenium, glutathione peroxidase (GPX; EC 1.11.1.9), ConA-bound selenium (CABS), and alpha 1-acid glycoprotein (AAG) were determined in normal subjects and patients with various pathological conditions. CABS accounted for 44.1% +/- 6.3% of total selenium in sera from normal subjects and 46.5% +/- 3.9% to 55.1% +/- 8.1% in sera from patients with a variety of diseases. Total selenium in serum was well correlated with serum CABS (r = 0.860), but not with serum GPX activity (r = 0.117), for all patients studied. Serum CABS increased in normal subjects after selenium supplementation. Serum CABSP did not behave as an acute-phase reactant, compared with AAG.
11270517 Circulating immune complex levels measured by new ELISA kits utilizing monoclonal anti-C1q 1992 The authors studied sera from both patients with SLE and from those with RA to evaluate clinical usefulness and significance of circulating immune complexes (CIC) detected with new ELISA kits utilizing monoclonal anti-C1q and anti-C3d antibodies. CIC values of patients with SLE significantly correlated to severity of disease activities evaluated by clinical symptoms and laboratory tests, especially for serum complement levels. Since substances detected with the ELISA kits were closely related to serum complement components, it was determined that a direct relationship exists between clinical activities and CIC values appearing in SLE patients with hypocomplementemia. In RA patients, CIC values did not correlate to clinical activities evaluated by Lansbury's index, anatomical bone damage with X-ray or functional assessment of activities of daily living, but did significantly correlate to levels of IgM-RF, serum IgG concentrations and some markers of systemic inflammation. Detection of IC after fractionation of RA sera revealed a broad range of molecular sizes detectable with the ELISA kits, which indicated that CIC in vivo were heterogenic and complicated in formation, degradation and interaction with serum complements.
7538297 Large and small proteoglycans of osteoarthritic and rheumatoid articular cartilage. 1995 May OBJECTIVE: To identify characteristic changes in large aggregating (aggrecan) and small proteoglycan (PG) populations in articular cartilages during osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: Aggrecan populations in guanidine extracts of femoral condylar cartilages of 46 OA and 8 RA patients who underwent total knee arthroplasty, as well as of 2 fetuses and 6 normal adults, were separated in agarose-polyacrylamide composite gels. Small PGs (biglycan, decorin, and fibromodulin) in the same extracts were analyzed in 12% polyacrylamide gels. Gels were stained or electrophoretically transferred and probed with antibodies to aggrecan epitopes and to small PGs. Epitope contents of the samples were also compared by inhibition radioimmunoassay. RESULTS: There were significant differences found among normal and diseased samples in their electrophoretic mobilities, band distributions, and antibody staining. OA and especially RA samples were heavily degraded, lacked certain aggrecan populations, and contained fewer keratan sulfate and chondroitin-6-sulfate epitopes compared with normal samples. Levels of chondroitin-4-sulfate and "fetal-type" epitopes were elevated in the OA samples compared with the normal ones. More core proteins of small PGs were found in diseased than in normal cartilages, but they were more heterogeneous in size and glycosaminoglycan substitution. CONCLUSION: There is extensive degradation of both large and small PGs in diseased cartilages, but a repair process does exist, especially in OA cartilages. Chondrocytes of diseased cartilages are able to synthesize fetal-type aggrecans. Small PGs are glycosylated differently in diseased cartilages than in normal ones.
8933113 Validation of a particle enhanced immunoturbidimetric assay for serum beta 2-microglobulin 1996 Oct We describe the development and validation of a fully automated homogeneous immunoassay for serum beta 2-microglobulin on the Dade aca clinical analyzer. The assay employs latex enhanced immunoturbidimetry, with an affinity purified polyclonal antibody covalently coupled to a 40 nm latex particle. The assay working range is < 0.5 to 20 mg/l with no evidence of loss of signal due to antigen excess at concentrations up to 120 mg/l. The assay sensitivity is 0.2 mg/l; within run and between run imprecision showed coefficients of variations of < 7%, across the assay range 1-20 mg/l. A method comparison with an established RIA procedure gave a regression equation of (aca) = 1.14 (RIA)-0.26, r = 0.996, n = 109. Good analytical recovery (98-101%), no evidence of a lack of parallelism and no interference from rheumatoid factor (tested up to 1.2 x 10(6) U/l) were observed. The low method to be considered as an effective means of monitoring seroconversion in HIV infected subjects and treatment of patients with myelomatosis.
7882555 Synovial cells are potent antigen-presenting cells for superantigen, staphylococcal entero 1995 Mar There is ample evidence suggesting that superantigens may act as a triggering factor in the pathogenesis of rheumatoid arthritis (RA). We investigated whether superantigen could activate T cells in the presence of synovial cells. T cells were cultured with SEB in the presence of interferon-gamma (IFN-gamma)-treated synovial cells. T cell proliferation and activation were assessed by 3H-thymidine incorporation and IL-2 production. The expression of HLA class II antigens and adhesion molecules on synovial cells was detected by flow cytometer. In the presence of IFN-gamma-treated synovial cells, T cells proliferated vigorously and produced IL-2 in response to SEB. A low SEB-induced T cell response was noticed in the presence of untreated synovial cells. Allogeneic as well as autologous IFN-gamma-treated synovial cells markedly enhanced SEB-induced T cell proliferation. IFN-gamma-treated synovial cells had increased expression of HLA class II antigens and intercellular adhesion molecule-1 (ICAM-1) adhesion molecules. MoAbs towards these antigens markedly inhibited the SEB-induced T cell response. These results indicate that activated synovial cells are potent antigen-presenting cells for SEB to T cells, and that superantigens may play a critical role in the pathogenesis of RA through activated synovial cells.
8154406 A review of selected newer nonsteroidal anti-inflammatory drugs. 1994 Apr Development of nonsteroidal anti-inflammatory drugs (NSAIDs) with a goal of improved efficacy and lower toxicity has continued, resulting in the introduction of etodolac, ketorolac, nabumetone and oxaprozin on the market. Each of these agents appears to be as effective as other commonly used NSAIDs in the treatment of rheumatoid arthritis or osteoarthritis. Studies of nabumetone and etodolac show a lower incidence of serious gastrointestinal toxicity with both drugs, but additional large clinical trials are necessary to confirm these findings. Although ketorolac, which is now available in oral form, is an effective analgesic, its long-term use is limited by a high incidence of gastrointestinal toxicity. Oxaprozin is an effective, long-acting anti-inflammatory analgesic, but its comparative advantages remain undefined.
7567010 Transoral-transpharyngeal approach to the craniocervical junction. 1995 Oct The transoral-transpharyngeal approach is a reliable and technically sound method for gaining anterior extradural exposure to the craniocervical junction. We report 23 patients undergoing this approach for pathology lying between the inferior clivus and third cervical vertebra. Pathology included 6 patients with congenital malformations of the odontoid process, 4 patients with basilar invagination caused by rheumatoid arthritis, 2 patients with atlantoaxial subluxation caused by Down's syndrome, and 1 each with Chiari I malformation, pseudogout of C1/C2, ossification of the posterior longitudinal ligament, and chronic dens dislocation caused by trauma. Malignant tumors included 4 chordomas, 2 giant cell tumors of C1-C3, and 1 chondrosarcoma. Orotracheal intubation without tracheotomy was used in 22 patients. Sixteen of these 22 patients were extubated either immediately or within 24 hours. Six complications occurred in 5 patients and included a palatal dehiscence in 2, delayed oropharyngeal hemorrhage, prolonged endotracheal intubation because of severe tongue edema, and 1 case each of meningitis and aspiration pneumonia responsive to intravenous antibiotics. No deaths, local infections, or postoperative cerebrospinal fluid leaks occurred. Neurologic symptoms of cord compression improved or stabilized in all patients. The transoral-transpharyngeal approach is an effective means for extradural decompression of the anterior craniocervical junction and for exposure of selected tumors at this site.
8484105 Aggregated human immunoglobulins bind to modified proteins. 1993 May Human immunoglobulins treated at 55 degrees C in vitro are able to interact with maleylated bovine serum albumin (mBSA), but not with unmodified BSA. Gel filtration experiments demonstrated that the mBSA binding is associated with a high molecular weight complex of aggregated IgG. This aggregated IgG with binding capacity for mBSA could also be generated in vitro by treatment of human IgG at 37 degrees C or 40 degrees C and by incubation with human neutrophils. Furthermore, IgG aggregates with binding activity for mBSA could be detected in untreated synovial fluids from rheumatoid arthritis patients, indicating that these complexes occur in vivo. The phenomenon of binding to aggregated IgG was extended to other modified proteins such as maleylated human serum albumin (mHSA), acetyl low density lipoprotein (Ac-LDL) and BSA reacted with oxidized linolenic acid. Soluble forms of these modified proteins were able to compete for the interaction between aggregated IgG and surface-bound mBSA. We also found that aggregated IgG enhanced the Ac-LDL-dependent foam cell formation. These findings suggest a role for aggregated IgG in the metabolism of oxidized proteins.
8981096 An improved ELISA for the determination of sialyl Lewis(x) structures on purified glycocon 1996 Dec The membrane carbohydrate antigen, sialyl Lewis x (sLe(x)), is involved in cellular adhesive interactions in many diseases, such as cancer, inflammation and thrombosis. This antigen is also found on soluble macromolecules, such as serum glycoproteins, but the precise role of soluble sLe(x) in modifying disease processes, or reflecting the pathological changes is still unclear. Although methods were previously reported for the measurement of soluble sLe(x), many of these were not well characterised, measurements were mainly made on mixtures of molecules, and the anti-sLe(x) antibodies were used at concentrations that made the assay expensive. In this study an ELISA has been devised that detects sLe(x) in purified soluble glycoconjugates using the anti-sLe(x) antibody, CSLEX I. Commercially-available haptoglobin (Hp) and synthetic complexes of Lewis antigens with polyacrylamide were used as model substances in developing the procedure. Key steps were washing the antibody/antigen complex with ten times diluted salt solution to prevent dissociation of the complex and the use of bovine serum albumin for blocking non-specific interactions. The assay was shown to be very specific, its precision was in the range 6-12%, and it could detect less than a pmol of sLe(x). It could also distinguish between different densities of sLe(x) on the same amount of glycoconjugate. Determination of sLe(x) in Hp isolated from small groups of healthy individuals, cancer patients, and rheumatoid arthritis sufferers suggested that the antigen expression is increased in disease. This method, which is an improvement on those previously described will be useful for determining sLe(x) in many different types of soluble glycoconjugate, and used in combination with synthetic carbohydrate polyacrylamide complexes, will help to standardize measurements of soluble sLe(x) in the future.