Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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8970191 | Morphology, function and pathology of follicular dendritic cells. | 1996 Nov | The precise ultrastructural morphology and functions in reactive conditions of lymphoid follicles (LF) and dendritic cells, including follicular dendritic cells (FDC) are reviewed; as well as the pathognomonic role of FDC in some disease conditions and finally, the cellular origin of FDC. In reactive conditions, FDC in each of the five follicular zones have distinct ultrastructural features, reflecting the different three-dimensional structures and functions of these zones. The FDC framework may be supported by some characteristic factors, including desmosome-like junctions between FDC and the expression of fibronectin and laminin receptors and caldesmon on FDC. FDC, especially in the light zone, express various cytokine receptors, but produce only one cytokine, TGF-beta. The outer zone may not only be a cellular pathway in the LF, but may also provide a site for germinal center B cell proliferation, and the FDC-lymphocyte cluster is not the site of germinal center B cell division. In patients with auto-immune diseases, such as Hashimoto's thyroiditis and rheumatoid arthritis, FDC may be in a hyperfunctional state, whereas those in patients with immunosuppressive disorders, such as Kimura's disease and AIDS, may be in a dysfunctional state. FDC may be derived from fibroblastic reticulum cells in lymphatic tissues rather than in bone marrow cells. The data discussed in this review provide fascinating insight into the roles of FDC, which are intimately related to the migration, proliferation, cell selection and differentiation of B cells in secondary LF. | |
8933282 | No evidence for autoimmunity in schizophrenia. | 1996 Oct | We studied parameters of cellular immunity in 23 schizophrenic patients and compared them to 16 matched healthy controls and to 12 patients with rheumatoid arthritis (RA). None of the patients was receiving neuroleptic drug treatment before the study. We used highly sensitive methods to examine the interferon system by determination of the interferon-induced enzyme 2'-5' oligo-adenylate synthetase [2-5A] in peripheral blood mononuclear cells. Tumor necrosis factor alpha (TNF-alpha) production was measured in the plasma and in vitro by bioassay of supernatants of stimulated blood cells and of unstimulated cells (spontaneous TNF secretion). In addition, we determined cell-mediated (spontaneous) cytotoxicity, major T cell subsets (CD3, CD4 and CD8 positive cells) and serum neopterin levels. No statistically significant differences could be found between the patients with schizophrenia and the control group in any of the tests used, and no particular subgroup of patients could be identified. In contrast, RA patients had increased serum neopterin and TNF levels, increased LPS-induced TNF production in vitro, increased 2-5A levels and a decrease in CD8 cells associated with an increase in CD4 cells. Thus, in the group of patients studied, we could find no substantiation for the presence of either autoimmune or occult viral cofactors in the pathogenesis of schizophrenia. | |
8693459 | [Quality control of prosthetic replacements of knee, ankle, toe, shoulder, elbow and finge | 1996 Jun 10 | Total hip replacements have been recorded in the Norwegian Arthroplasty Register since 1987, and recording of the other joint arthroplasties was started in January 1994. After 12 months 1,589 primary arthroplasties had been registered; these referred to 962 knees, 11 ankles, 76 toes, 113 shoulders, 69 elbows, 12 wrists, 335 fingers and 11 carpometacarpal 1 joints. Median age of the patients was 70 years. 80% were women. Rheumatoid arthritis was the predominant reason for joint replacement, except in the case of the knees where the dominant cause was osteoarthrosis (71%) and of shoulders, 28% of which were replaced because of fractures. Cement was used in 83% of the primary arthroplasties in knee, ankle, shoulder, and elbow joints. 74% of the cement types used contained antibiotics. 9% were uncemented and 8% hybrids. 97% were given systemic antibiotic prophylaxis, most commonly first generation cephalosporins. 114 reoperations were reported. The reason was aseptic loosening in 56%, and infection in 15%. The cooperation with Norwegian orthopaedic surgeons is good. The Register thus provides a reliable picture of implants of Norway, and a good basis for future follow-up studies. | |
8732992 | Clinical aspects of glucocorticoid sensitivity. | 1996 Apr | Recent studies demonstrate that primary (hereditary) abnormalities in the glucocorticoid receptor gene make 6.6% of the normal population relatively "hypersensitive" to glucocorticoids, while 2.3% are relatively "resistant." These abnormalities might explain why some individuals develop severe adverse effects during low dose glucocorticoid therapy, while others do not develop side effects even during long-term therapy with a much higher dose. Awareness of this heterogeneity in glucocorticoid sensitivity in the normal population might eventually allow the prediction of a "safe" dose of glucocorticoid in individual patients. "Resistance" to the beneficial clinical effects of glucocorticoid therapy in part of the patients with severe rheumatoid arthritis and asthma is probably rarely related to generalized primary (hereditary) glucocorticoid resistance. In the majority of patients this "resistance" seems to be acquired and localized to the sites of inflammation, where it reflects high local cytokine production, which interferes with glucocorticoid action. Recognition of localized, acquired glucocorticoid resistance is of great importance indicating as alternative drug therapy with other immune-modulating drugs like cyclosporin and methotrexate. Chronic high dose glucocorticoid treatment in such patients is ineffective in alleviating symptomatology, while generalized side effects occur, reflecting the patient's normal systemic sensitivity to these drugs. | |
8718715 | The effect of bone quality on the outcome of ingrowth total knee arthroplasty. | 1996 Spring | Bone quality generally is felt to be an important consideration when planning total knee arthroplasty (TKA). This prospective study was conducted to see if bone quality, as assessed intraoperatively in 346 knees, affects the outcome of ingrowth TKA. Group A consisted of 272 knees with good or excellent bone quality in all areas and Group B consisted of 74 knees with fair or poor bone in at least one area. The average follow-up was 48 months, with 301 knees (87%) available for follow-up. Group A knees had more males, were heavier, had fewer patients with rheumatoid arthritis, and exhibited more varus. Preoperatively, Groups A and B had modified Hospital for Special Surgery (HSS) knee scores that averaged 55 and 48, respectively. At 4 years post-surgery, Groups A and B had HSS scores of 92 and 90, respectively. Fluoroscopic radiographs of the bone-prosthesis interfaces showed 13% incomplete radiolucencies in Group A and 7% in Group B. A complete radiolucency was seen in one patient in Group A. Based on these results, it can be concluded that bone quality as determined by gross intraoperative inspection had little effect on the 4-year outcome of this ingrowth TKA. | |
8665478 | Human endogenous retroviruses: nature, occurrence, and clinical implications in human dise | 1996 Jan | Retroviral diagnostics have become standard in human laboratory medicine. While current emphasis is placed on the human exogenous viruses (human immunodeficiency virus and human T-cell leukemia virus), evidence implicating human endogenous retroviruses (HERVs) in various human disease entities continues to mount. Literature on the occurrence of HERVs in human tissues and cells was analyzed. Substantial evidence documents that retrovirus particles were clearly demonstrable in various tissues and cells in both health and disease and were abundant in the placenta and that their occurrence could be implicated in some of the reproductive diseases. The characteristics of HERVs are summarized, mechanisms of replication and regulation are outlined, and the consistent hormonal responsiveness of HERVs is noted. Clear evidence implicating HERV gene products as participants in glomerulonephritis in some cases of systemic lupus erythematosus is adduced. Data implicating HERVs as etiologic factors in reproductive diseases, in some of the autoimmune diseases, in some forms of rheumatoid arthritis and connective tissue disease, in psoriasis, and in some of the inflammatory neurologic diseases are reviewed. The current major needs are to improve methods for HERV detection, to identify the most appropriate HERV prototypes, and to develop diagnostic reagents so that the putative biologic and pathologic roles of HERVs can be better evaluated. | |
7633793 | OM-89 modulation of chronic inflammation: relevance to clinical use. | 1995 Jun | The modulatory effects of a glycoprotein-rich endotoxin-free extract of Escherichia coli (OM-89) have been studied using the cotton pellet model of chronic inflammation in the male Wistar rat. OM-89 had a suppressive effect on the size of granuloma surrounding implanted cotton pellets at both 4 and 40 mg/kg given three times weekly. The lower dosage of 4 mg was effective throughout and there was little to be gained by increasing the dose as further reduction of granuloma size was not obtained. Whether given prior to, at the same time as, or after an inflammatory stimulus, OM-89 had suppressive effects. However, if given before, animals at first went through a phase of 'sensitization' before suppressive effects were seen on further exposure to OM-89 antigens, a phenomenon which might have bearing on clinical findings in rheumatoid arthritis. In animals presensitized to a cotton pellet, OM-89 was statistically as effective as indomethacin in suppressing a second granuloma. OM-89 combined with indomethacin showed additive effects and was highly effective. The results indicate that OM-89 could be efficacious in the treatment of chronic inflammatory conditions and there is the possibility that in appropriate circumstances OM-89 might replace some drugs currently used and in others reduce their dosage. | |
7844466 | The lymphocyte chemoattractant factor. | 1995 Feb | The LCF is a unique interleukin without significant homology to other interleukins or chemokines. It is a chemoattractant factor for all CD4+ cells and either uses CD4 as its receptor or utilizes a cell surface complex of molecules for which there is an absolute requirement for the presence of CD4. In addition to its chemoattractant activity, it is a growth factor for CD4+ T cells, inducing resting cells to enter G1, as evidenced by the expression of MHC II molecules and IL-2R. Once induced by LCF to express IL-2R, CD4+ T cells become competent to respond to LCF and progress through the cell cycle to proliferation. LCF's activity on CD4 cells defines a role for CD4 on the eosinophil and monocyte and broadens the scope of functions of CD4 on the T cell. In this regard it may have importance in human disease states that are characterized by increased numbers of activated CD4+ cells, such as sarcoidosis, rheumatoid arthritis, or asthma. Likewise, it may play a key role in monocyte and eosinophil chemotaxis into tissues, being important in the latter in concert with hematopoietic factors that increase the available eosinophil pool. | |
7720377 | Skin testing with gold sodium thiomalate and gold sodium thiosulfate. | 1995 Jan | Recently gold sodium thiosulfate was found to be the most common sensitizer after nickel sulfate in our routinely patch tested dermatitis patients. When patients hypertensive to gold sodium thiosulfate were tested with another monovalent gold salt, gold sodium thiomalate, at equimolar concentrations, in principle, no positive reactions were obtained. Gold sodium thiomalate is used for treatment of rheumatoid arthritis, a treatment with a high frequency of adverse skin reactions. To investigate whether the reactivity difference between the 2 gold salts was due to differences in bioavailability, some experiments were carried out. Intracutaneous tests with the 2 gold salts at equimolar concentrations yielded equivalent reactions. When the concentration of gold sodium thiomalate for epicutaneous testing was increased, all 12 gold-allergic patients reacted positively. Therefore, in our department, contact allergy to gold sodium thiomalate is probably as common as contact allergy to gold sodium thiosulfate. | |
7808428 | Paradoxical derepression of collagenase gene expression by the antirheumatic gold compound | 1994 Dec | The neutral metalloproteinase collagenase is known to be, among others, one of the key enzymes promoting joint destruction in patients with rheumatoid arthritis. Because inflammatory cytokines, e.g., interleukin-1 and tumor necrosis factor-alpha, are considered to activate collagenase gene expression through activation of the transcription factor activator protein-1, we examined whether the water-soluble gold compound aurothiomalate (AuTM) influenced collagenase gene expression, using phorbol ester-treated human fibroblasts. However, AuTM did not prevent phorbol ester-mediated activation of activator protein-1 DNA-binding activity and subsequent induction of collagenase gene expression. In contrast, AuTM counteracted the repressive effects of glucocorticoids on collagenase gene expression and restored collagenase mRNA levels. The molecular target of this paradoxical AuTM action was suggested to be the glucocorticoid receptor. | |
8090592 | Anti-neutrophil cytoplasmic antibodies (ANCA): their detection and significance: report fr | 1994 Apr | Anti-neutrophil cytoplasmic antibodies (ANCA) are antibodies directed against enzymes that are found mainly within the azurophil or primary granules of neutrophils. There are 3 types of ANCA that can be distinguished by the patterns they produce by indirect immunofluorescence when tested on normal ethanol-fixed neutrophils. Diffuse fine granular cytoplasmic fluorescence (cANCA) is typically found in Wegener's granulomatosis, in some cases of microscopic polyarteritis and Churg Strauss syndrome, and in some cases of crescentic and segmental necrotising glomerulonephritis, but it is rare in other conditions. The target antigen is usually proteinase 3. Perinuclear fluorescence (pANCA) is found in many cases of microscopic polyarteritis and in other cases of crescentic and segmental necrotising glomerulonephritis. These antibodies are often directed against myeloperoxidase but other targets include elastase, cathepsin G, lactoferrin, lysozyme and beta-glucuronidase. The third group designated "atypical" ANCA includes neutrophil nuclear fluorescence and some unusual cytoplasmic patterns, and while a few of the target antigens are shared with pANCA, the others have not been identified. Sera that produce a pANCA or atypical ANCA pattern on alcohol-fixed neutrophils result in cytoplasmic fluorescence when formalin acetone fixation is used. pANCA or atypical ANCA occur in about 2/3 of all individuals with ulcerative colitis or primary sclerosing cholangitis, and they are found in a third of patients with Crohn's disease. The reported incidence of ANCA in rheumatoid arthritis and SLE varies considerably but the patterns are predominantly pANCA and atypical ANCA.(ABSTRACT TRUNCATED AT 250 WORDS) | |
8023172 | The use of radiolabeled nonspecific immunoglobulin in the detection of focal inflammation. | 1994 Apr | The serendipitous discovery that radiolabeled nonspecific immunoglobulin G (IgG) accumulates at a site of focal inflammation has led to the development of a new radiopharmaceutical for inflammation scanning, 111In-IgG. This reagent has been extensively studied in humans with focal infection and has been shown to be both safe and effective. It has been especially useful in the evaluation of patients with possible abdominal and skeletal infection, with the ability to perform serial scans being an important attribute in terms of determining "proof of cure." Preliminary data suggest that this approach may be particularly useful in immuno-compromised patients and may find a role in the quantitative assessment of patients with such noninfectious inflammatory processes as rheumatoid arthritis and inflammatory bowel disease. A new method of labeling IgG with technetium, via the hydrazino nicotinamide derivative, holds promise in terms of substituting this more practical radionuclide for indium. However, caution must be directed against total substitution, because such processes as suspected vascular or skeletal prosthesis infection may require the longer half-life of 111In for satisfactory diagnosis. When one compares the results obtained with radiolabeled IgG against the ideal specifications for a radiopharmaceutical to be used for inflammation imaging, most of the requirements are met. The major weakness of this approach is that even with the technetium-labeled reagent, a minimum of 6 to 12 hours is necessary for a scan to become positive, which is not acceptable in the evaluation of acutely evolving processes. Development of other radiopharmaceuticals for this purpose remains to be accomplished. | |
9422113 | Quantitation of soluble HLA-DR antigens in human serum and other body fluids. | 1994 | The existence of soluble forms of MHC class II molecules is well established. To quantify soluble HLA-DR antigens (sHLA-DR) in human serum and other body fluids, we developed an enzyme immunoassay using two non-overlapping HLA-DR-specific monoclonal antibodies (RoDR, BL-la/5) and an immunoaffinity chromatography-purified sHLA-DR standard. In serum of healthy individuals, sHLA-DR levels were found in the range between 0.6 and 3 ng/ml (median 0.85 ng/ml) whereas EDTA plasma samples showed concentrations about 20 times higher (median 21 ng/ml). In tears, saliva, sweat, urine, amniotic fluid, cerebrospinal fluid, and bronchoalveolar lavage, sHLA-DR could also be detected. No association was found between sHLA-DR serum levels and distinct HLA specificities. In the sera of patients with autoimmune diseases, slightly enhanced sHLA-DR values were found (juvenile rheumatoid arthritis: median 2.0 ng/ml, lupus erythematosus: 1.5 ng/ml, diabetes mellitus: 2.1 ng/ml). | |
8378786 | [Results of cementless implantation of 150 "Erlangen Model" hip prostheses of titanium all | 1993 Aug | Between March 17, 1984 and August 20, 1987, 142 patients with osteoarthritis of one or both hips were treated by joint replacement with the uncemented "Erlangen" hip prosthesis (Prof. H. Beck/P. Brehm Chirurgie-Mechanik GmbH). The causes of the osteoarthritis varied. Hip replacement was carried out for the following conditions: rheumatoid arthritis including ankylosing spondylitis, aseptic necrosis of the femoral head, including posttraumatic and idiopathic forms, osteoarthritis of unknown origin, osteoarthritis following dysplasia or subluxation of the hips, and loosened cemented hip prostheses (131 primary implantations and 19 revisions). Full weight-bearing was not permitted for 50 days postoperatively, but mobilization and isometric exercises were started 2 days after operation and isotonic exercises were introduced later. Complications included fracture of the femoral shaft during operation and aseptic loosening. Our results in the 142 patients (150 joints) at 32-65 months (average 44 months) after surgery are encouraging. Good results based on patient satisfaction were obtained in 92.7% (81.3% after revision) and poor results in 7.3% (18.7% after revision). Most (90.2%) of the patients can walk without a stick (50.0% after revision), and 90.2% of the patients can walk more than 1000 m (68.8% after revision). | |
1490736 | Self-reactive and antigen-specific T cell clones derived from a HLA-DR4+/DR5+ donor: T cel | 1992 Nov | The relationship of heat shock proteins and rheumatoid arthritis as well as the relevance of autoreactivity in this disease is unclear. T cells of six individuals (four expressing the DRB1*0401 allele, one harboring DRB1*0404 and one the DRB1*0407 allele) were cloned in the presence of 65kD mycobacterial heat shock protein (HSP60) in order to determine T cell receptors (TcR) used and the MHC class II restriction patterns of potentially relevant T cell clones (TcC). All TcC obtained were not specific for HSP60, but six TcC of one donor (HLA-DR4/HLA-DR5) were responsive towards autologous antigen-presenting cells. One TcC displayed authentic autoreactivity whereas five TcC reacted specifically to serum proteins. The amino acids (aa) of the MHC molecule, crucial for immune recognition were mapped to aa #71 or #86 of either maternal or paternal origin. The strictly autoreactive TcC did not recognize transfected L cells implicating specificity for self-peptides not presented by L cells or the involvement of adhesion molecules. Correlations between autoreactivity and TcR V(D)J sequences or N nucleotides of various "autoreactive" TcC were not evident. | |
1479713 | [A case of primary amyloidosis associated with giant cell infiltration within a Bowman's c | 1992 Jun | A 67-year-old man was hospitalized with a diagnosis of nephrotic syndrome. Physical findings at admission were generalized edema and macroglossia. Urinalysis showed massive proteinuria, + +occult blood, and granular and broad casts. Ig A lambda monoclonal gammopathy was noted in the serum. There was no evidence of myeloma in the bone marrow aspirate, scintigram or X-ray of the bone. A biopsy specimen of the kidney showed massive deposits of structureless material in the glomeruli. Marked cell infiltration was also observed in the interstitium. Multinucleated giant cells were occasionally seen in the Bowman's capsules and the interstitium. There were reactive changes in the Bowman's capsule adjacent to the giant cell. The deposits were proved to be amyloid by positive staining with Congo red and apple-green birefringence by polarized light. In addition, microfibrills seen on electron microscopy displayed deposits. Amyloid depositions were observed in other tissues such as gingiva, skin and tongue. Staining of amyloid with Congo red was resistant to potassium permanganate, and amyloid was positively stained with lambda-light chain of immunoglobulin. These findings indicated that the patient had primary amyloidosis. Infiltration of the multinucleated giant cell has been reported only in patients with familial amyloidosis and secondary amyloidosis associated with rheumatoid arthritis. To our knowledge the present case is a first report of the giant cell infiltration in a Bowman's capsule in primary amyloidosis. | |
1404125 | IgG autoantibody to the collagen-like region of Clq in hypocomplementemic urticarial vascu | 1992 Jun | We previously found that the Clq precipitin in sera from patients with hypocomplementemic urticarial vasculitis syndrome is an IgG autoantibody to Clq. We report here a prevalence study of this autoantibody in 162 patients with musculoskeletal or rheumatic diseases including hypocomplementemic urticarial vasculitis syndrome, systemic lupus erythematosus (SLE), and rheumatoid arthritis uncomplicated by vasculitis. The autoantibody, which binds only to the collagen-like region of Clq, was found almost exclusively in hypocomplementemic urticarial vasculitis syndrome (100%) and SLE (35%) sera. Our results support the idea that among rheumatic diseases, anti-Clq autoantibody develops in disorders characterized by immune complex mediated injury, particularly of cutaneous and glomerular microvasculature. | |
1376260 | Molecular cloning and expression of the murine RANTES cytokine: structural and functional | 1992 Jun | The infiltration and activation of monocytes is a hallmark of chronic inflammation, including that associated with a variety of disease states such as rheumatoid arthritis, atherosclerosis, and various autoimmune conditions. Recently, a family of small molecular mass proteins has been described which appear to have inflammatory properties, including chemoattractant effects on monocytes. We report here on the molecular cloning, characterization, and functional expression of mu RANTES, a new murine member of this family. mu RANTES expressed in a mammalian expression system is an approximately 8-kDa protein exhibiting immune cross-reactivity with a rabbit polyclonal antiserum generated against human RANTES. Boyden chamber chemotaxis experiments reveal some lack of species specificity in monocyte chemoattractant potential, as recombinant mu RANTES attracts human monocytes in a dose-dependent fashion in vitro. mu RANTES and its human homolog share approximately 85% amino acid identity, a higher level of conservation than that seen with any other species homologs in this cytokine family, and second only to transforming growth factor-beta among reported immune cytokines. | |
1732900 | The effect of low-energy laser on skin-flap survival in the rat and porcine animal models. | 1992 Feb | Low-energy lasers are currently being used in the therapy of rheumatoid arthritis, chronic pain, muscle strain, and the promotion of wound healing in human and veterinary medicine. This study examined the effects of low-energy laser on skin-flap survival in a controlled interspecies study using the rat and porcine models. Twenty dorsal skin flaps based caudally were performed in 20 rats (10 laser-treated and 10 control flaps). The wounds were closed, and the flaps were sutured over the skin. Forty dorsal pig skin flaps based medially were raised in five pigs. The flaps were treated once per day for 10 days: 4 days preoperatively, the day of surgery, and 5 days postoperatively (30 s/cm3 per day). The average surviving rat flap surface area for the laser-treated flaps was 653 +/- 112 mm (mean +/- SD) and 580 +/- 60 mm in the control flaps, which was not significant (p greater than 0.05). In the porcine model, the average surviving area for the 20 laser-treated flaps was 949 +/- 174 mm, and the control average (n = 20) was 969 +/- 147 mm, also not significant. No beneficial effect was seen with low-energy laser preoperative and postoperative treatment of skin flaps in the rat and porcine models. | |
1371260 | Angiogenesis in the female reproductive system. | 1992 Feb 1 | In adult tissues, capillary growth (angiogenesis) occurs normally during tissue repair, such as in healing of wounds and fractures. Rampant capillary growth is associated with various pathological conditions, including tumor growth, retinopathies, hemangiomas, fibroses and rheumatoid arthritis. The female reproductive organs (i.e., ovary, uterus, and placenta) exhibit dynamic, periodic growth and regression accompanied by equally dramatic changes in rates of blood flow. It is not surprising, therefore, that they are some of the few adult tissues in which angiogenesis occurs as a normal process. Thus, the female reproductive system provides a unique model for studying regulation of angiogenesis during growth and differentiation of normal adult tissues. Ovarian, uterine, and placental tissues recently have been shown to contain and produce angiogenic and anti-angiogenic factors. This review discusses the current state of knowledge regarding angiogenic processes and their regulation in female reproductive tissues. In addition, implications of this research for regulation of fertility as well as for control of angiogenesis in other normal and pathological processes are discussed. |