Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1746715 | Fine structure of the human synovial lining cell in osteoarthritis: its prominent cytoskel | 1991 Oct | The cytoskeleton of the human osteoarthritic synovial lining cell (SLC) consists of an extensive number of vimentin intermediate filaments (IFs) in addition to microfilaments and microtubules. The IFs are especially prevalent in the SLC processes, but are commonly seen in a paranuclear arrangement. Processes, ending in numerous microvilli and blebs, project into the joint space. Scanning electron microscopy (SEM) further reveals the processes that may parallel the synovium surface for a short distance. IFs extend to the termination of such Numerous pinocytotic vesicles and extensive rough endoplasmic reticulum (rER) are characteristic of the type B cells. Lysosomes and long microvilli identify the type A cell. Punctate adherens, gap junctions, and cilia are the cell membrane specializations of the osteoarthritis (OA) synovium. A comparison with synovium from rheumatoid arthritis (RA) patients is made in order to assess the effect o this inflammatory disease on the SLC cytoskeleton, cell type relationship, and cell arrangement. The prominent cytoskeleton appears to play an important role in the architecture of the synovium. Our findings are further presented in the form of a drawing which in some aspects could describe the morphology of the normal synovium. | |
| 1654118 | Transforming growth factor beta stimulates the production of the tissue inhibitor of metal | 1991 Sep 3 | IL-1 stimulates the secretion of metalloproteinases by a variety of connective tissue cells and is thought to be the primary inducing agent of connective tissue breakdown in rheumatoid arthritis. Transforming growth factor-beta (TGF-beta) is known to be capable of inhibiting the synthesis of metalloproteinases and to be able to partially inhibit interleukin-1 (IL-1) induced cartilage degradation. The present paper examines the ability of TGF-beta to modulate the action of IL-1 on fibroblasts of synovial and skin origin and investigates the secretion of the tissue inhibitor of metalloproteinases (TIMP) by these cells after exposure to TGF-beta and IL-1. The principal findings are that when four out of five fibroblast lines were exposed to TGF-beta and IL-1 in combination they displayed a significant increase in TIMP secretion; furthermore, in two of these cell lines a significant stimulation of TIMP secretion was induced by TGF-beta alone. | |
| 18415170 | [Psychological pain treatment in rheumatic patients.]. | 1991 Mar | Psychodynamic concepts postulate a psychogenesis of physical pain proposing several assumptions about the conversion of mental suffering into physical pain. Behavioural concepts, on the other hand, emphasize psychological conditions as risk factors for chronicity and describe psychological reactions to chronic pain. Patients with painful diseases and inadequate coping strategies very often display symptoms of anger, anxiety, or depression. Recently, the use of group therapy aimed at enhancing patients' ability to cope with disease-related stressful events has become widely accepted in behavioural medicine with a focus on pain-management procedures. Strategies for the improvement of coping with pain are based on behavioural, psychophysiological, and cognitive principles. The behavioural view conceptualizes pain as a behavioural problem with regard to facial and bodily expressions of pain, decreased physical and mental activity, and the consumption of pain medication. Operant conditioning is used to discourage pain behaviour and reinforce well-behaviour. The physiological concept stresses the vicious cycle of pain, increased muscle tension, and emotional reactions. Relaxation procedures are introduced in order to reduce excessive muscular activity in targeted muscles. The cognitive approach emphasizes the effect of information-processing on pain experience. Cognitive distortions are identified, and self-control management is encouraged. Having taken all of these aspects into consideration, we developed a cognitive-behavioural treatment programme in a group setting format with components of relaxation, cognitive restructuring, and the promotion of well-being. Subjects included in the study were given diagnoses of low back pain, tension headache, rheumatoid arthritis, and ankylosing spondylitis. Treatment effects in different diagnostic groups were compared to each other, supporting the assumption that pain reduction is greatest in low back pain and least in ankylosing spondylitis. Subjects with inflammatory rheumatic diseases showed some improvement in self-reported physical complaints and in their feelings of well-being. | |
| 2008219 | [Alternative treatment methods in rheumatic diseases; a literature review]. | 1991 Feb 23 | To evaluate the effectiveness of several types of complementary medicine in patients with rheumatic diseases, a literature search was performed. Clinical trials, blind or open, comparing the effectiveness of forms of complementary medicine with that of placebo or another control therapy in patients with rheumatoid arthritis, osteoarthritis, soft tissue rheumatism and the fibromyalgia syndrome were selected until half of 1989, using electronic databases. Abstracts and summaries were excluded. The investigation was performed at the department of rheumatology of the Medisch Spectrum Twente hospital at Enschede in cooperation with the department of internal diseases of the Sint Radboud hospital at Nijmegen. For each type of complementary treatment, the results of all the clinical trials were summarized. Furthermore, the placebo-controlled trials were graded according to convincing trials or trials that seemed to be less valid and/or difficult to interpret. Data concerning acupuncture, balneotherapy, dietary measures, enzymic therapy, Seatone, homeopathy, manual therapy and fever few were found. Of these types of complementary medicine in rheumatic diseases, we found no convincing prove that they are more effective than the control or placebo treatment. A considerable number of the studies however can be criticized. It is necessary to perform further studies on the effect of frequently used types of complementary medicine in patients with rheumatic diseases, by or in cooperation with the physicians or paramedics who prescribe or perform these kinds of treatment. This is nearly always possible; directives are given to realize further studies of this kind. If a particular treatment proves to be no more effective than placebo treatment, its use should be discouraged. | |
| 1772725 | Proliferative cell response to loosening of total hip replacements: a cytofluorographic ce | 1991 | Monocyte/macrophages and fibroblasts are the major reactive cells in the periprosthetic connective tissue in a loose totally replaced hip. Monocyte/macrophages are bone-marrow-derived, hematogenous cells, whereas mesenchymal fibroblasts replenish by local proliferation. The cell-cycle-phase frequency distribution therefore reflects the local mitotic fibroblast response to the loose total hip replacement (THR) implant. In 13 patients who underwent revision of a loose THR implant, most of the local cells were in the resting G0/G1 phase (88.1 +/- 6.3%, mean +/- SD), whereas 8.6 +/- 3.7% were in the S phase of the cycle, and 3.4 +/- 2.9% had already reached the G2/M phase. The highest DNA values were recorded in an osteoarthritic patient undergoing revision 4 years after the primary uncemented THR, while the lowest values were observed in a rheumatoid arthritis patient with a loose cemented prosthesis 15 years after the primary operation. The results suggest that the local proliferative fibroblast response in general is uniform and does not seem to depend on the type of prosthesis or the use of cement. The responses in aggressive granulomatous-type loosening and the common type of loosening were similar. | |
| 2225649 | Review of the all-polyethylene tibial component in total knee arthroplasty. A minimum seve | 1990 Nov | A retrospective analysis of 144 total knee arthroplasties was performed between 1975 and 1981 with a minimum follow-up period of seven years. A posterior cruciate condylar prosthesis was used in each procedure. Patients were followed clinically and roentgenographically, and a set of statistical variables was established based on elevation in joint line, tibial component angular alignment, overall limb alignment, and position of the tibial component on anteroposterior and lateral roentgenograms. Review of the study group found that the Hospital for Special Surgery knee scores improved from a preoperative score of 55 to a postoperative score of 88, with 94.5% having good or excellent results. The mean postoperative range of motion was 106 degrees with a mean extension of -0.3 degrees. Radiolucencies developed in 41% of the knees with 5% of the knees having progressive radiolucencies. Eight knees were considered failures based on clinical and roentgenographic evaluations. Factors found to significantly affect the formation of radiolucent lines included a shift of the tibial component medially by greater than 4 mm, a varus tilt of the tibial component greater than 2 degrees, and the diagnosis of rheumatoid arthritis. The only variable associated with aseptic loosening was an elevation of the joint line by greater than 8 mm. | |
| 2125034 | The modulation of interleukin 1 production by interferon gamma, and the inhibitory effects | 1990 Sep | We have studied the in vitro effects of gold sodium thiomalate (GST) and auranofin (Auf) on the production of interleukin 1 (IL1) expressed as thymocyte co-stimulatory activity (TCSA), and interleukin 1 beta (IL1 beta) as modulated by interferon gamma (IFN gamma). Adherent cells (ADC), of which 80% were monocytes, were obtained from human peripheral blood, and stimulated with lipoprotein polysaccharide (LPS) for 24-48 h. TCSA and IL1 beta production by fresh ADC (0-24 h) was significantly higher than that of aged ADC (24-48 h). The addition of IFN gamma to ADC cultures, however, maintained the capacity of aging ADC to respond optimally to LPS. The addition of GST or Auf inhibited this modulatory effect of IFN gamma, resulting in a marked reduction of TCSA and IL1 beta production. The effects of IFN gamma on the production of IL1 may be important in the pathogenesis of rheumatoid arthritis (RA). The inhibition by GST and Auf of IFN gamma modulation may contribute to the therapeutic efficacy of these drugs in RA. | |
| 1696033 | [Studies on von Willebrand factor antigen in endothelial cells and sera of patients with c | 1990 Feb | Von Willebrand factor antigen (vWF: Ag) is known to be produced and excreted by endothelial cells (EC). The influences of interferon (IFN) on surface, excreted and intracellular vWF: Ag amounts of EC were studied by flow cytometry and ELISA. Serum levels of vWF: Ag in patients with connective tissue diseases were also studied by ELISA. Experiments in vitro showed that IFN increased vWF: Ag amounts of EC. Serum levels of vWF: Ag in patients with mixed connective tissue disease (MCTD), systemic lupus erythematosus, progressive systemic sclerosis, polymyositis/dermatomyositis or rheumatoid arthritis (RA) were significantly higher than those of normal subjects, on the other hand, vWF: Ag levels in patients with aortitis syndrome were within normal range. MCTD patients complicated with pulmonary hypertension (PH) [MCTD (PH)] and RA vasculitis (MRA) patients had quite high levels of vWF: Ag. The levels of vWF: Ag seemed to correlate with severity of PH in patients with MCTD (PH). Increased serum levels of vWF: Ag observed in those patients might be induced by EC damaged or influenced by IFN or other cytokines. Monitoring of vWF: Ag levels could be useful to predict the onset and pathologic conditions of MCTD (PH) or related vascular diseases. | |
| 2715873 | Microplate ELISA for detection of antibodies to DNA in patients with systemic lupus erythe | 1989 | A 96-well microplate ELISA for the detection of antibodies to DNA is described. A number of buffers and precoating treatments were used to evaluate the optimal method for coating the plate with DNA. These included pretreatment of the plates with poly-L-lysine or protamine sulfate, and posttreatment with glutaraldehyde, none of which improved the performance of the assay. Whereas bicarbonate and borate coating buffers gave equivalent and satisfactory results, TRIS buffer resulted in very high binding of immunoglobulin to wells not coated with antigen. Sera from groups of patients with autoimmune disease as well as normal sera were tested against plates optimally coated with native E. coli DNA, calf thymus DNA, and heat-denatured DNA. Using native E. coli DNA, virtually none of 35 normal sera had any detectable antibody. With this antigen, as well as with native calf thymus DNA, significant levels of DNA antibody were found only in SLE patients. Most patients with SLE or drug-induced lupus, as well as some patients with rheumatoid arthritis and normal individuals had antibodies that bound to heat-denatured (single-stranded) DNA. Using either native E. coli or calf thymus DNA, a good correlation was found between the amount of DNA antibody detected by ELISA and the Farr-type radioimmunoassay. | |
| 3178880 | Inhibition of glycosaminoglycan synthesis in anatomically intact rat patellar cartilage by | 1988 Oct 1 | We have studied the effect of low sulfate concentrations on the glycosaminoglycan synthesis in rat patellar cartilage in vivo as well as in vitro. The oral administration of 200 mg/kg paracetamol to male Wistar rats resulted in a significant reduction of the serum sulfate concentration. Reduced serum sulfate availability resulted in a 34% decrease of glycosaminoglycan synthesis in patellar cartilage. This is due to sulfate depletion since paracetamol had no direct effects on glycosaminoglycan synthesis and a slight but significant inhibitory effect on the catabolism of radiolabeled glycosaminoglycans in vitro. The glycosaminoglycans synthesized at low sulfate concentrations in vivo were similar to the glycosaminoglycans synthesized at physiological sulfate concentrations. Studying the effect of sulfate availability in vitro on glycosaminoglycan synthesis in patellar cartilage we found that incubation of rat patellae in medium containing less than 0.5 mM inorganic sulfate led to a decreased sulfate incorporation. The use of potential sulfate decreasing drugs can lead to inhibition of glycosaminoglycan synthesis. This argues for a reconsideration of the use of these drugs in patients with already dysfunctioning cartilage metabolism as in rheumatoid arthritis and osteoarthrosis. | |
| 3386844 | Clinical drawbacks of total lymphoid irradiation: the cons. | 1988 Jul | Success has been reported with use of total lymphoid irradiation (TLI) in organ transplant recipients and in patients with rheumatoid arthritis and other autoimmune diseases. In a well-conducted randomized double blind clinical trial, Cook et al have found that TLI was superior to sham irradiation of patients with multiple sclerosis (MS). However, it is clear from looking at this data that not all patients responded to TLI and that with time disease activity returned. Our own experience with TLI in two MS patients was very disappointing. Despite its apparent benefit in some conditions, considerable drawbacks are associated with TLI. These include high financial cost, unpleasant treatment-related side effects, and the possibility that more serious morbidity as well as mortality may be treatment-related. Furthermore, the optimum therapeutic regimen for TLI has not yet been established. Issues related to cumulative dose, dose per fraction, frequency of fractions, field of irradiation, and interaction with other therapies still need clarification. For these reasons we do not recommend TLI as a treatment for MS. | |
| 3139738 | Sodium aurothiomalate inhibits T cell responses to interleukin-2. | 1988 | We studied the effects of the gold compound sodium aurothiomalate (SATM) on the responses of murine CTLL2 cells, and human T cells to Interleukin-2 (IL-2). SATM inhibited tritiated thymidine (3HTdR) incorporation by CTLL2 cells stimulated with human recombinant IL-2. Human T cells were cultured with phytohemagglutinin (PHA) in separate experiments and IL-2 receptor expression measured by using immunofluorescent anti-Tac serum; SATM inhibited IL-2 receptor expression. Furthermore, SATM when added concurrently with PHA, and IL-2 inhibited 3HTdR incorporation by human T cells in 5 day cultures. The kinetics of inhibition were further studied by adding PHA to T cells for 48 hours followed by the addition of SATM and IL-2; SATM inhibited 3HTdR incorporation even though receptor expression had occurred. These results suggest that SATM inhibits the stimulatory effects of IL-2 on T cells partly by interfering with IL-2 receptor expression, and partly by other mechanisms of action. These effects of SATM may explain some of the conflicting data in the literature on T cell responses to IL-2 in rheumatoid arthritis (RA), and suggest a possible mechanism of action for the drug in the treatment of RA. | |
| 3319464 | Neutrophil function disorders. | 1987 Dec | The polymorphonuclear leukocyte (neutrophil) is the most important phagocytic cell that defends the host against acute bacterial infection. Disorders of neutrophil function are suggested by recurrent cutaneous, periodontal, respiratory, or soft tissue infections. Staphylococcus aureus, gram-negative bacilli, and less commonly, Candida albicans, are the causative organisms. Treatment is supportive involving surgical drainage and antibiotics. Bone marrow transplantation offers hope to some patients. The biochemical and molecular defects have been identified for some of these disorders. Identification of these defects and their physiologic consequences have improved our understanding of how the activated neutrophil is attracted and adheres to inflammatory sites, and produces toxic products that destroy bacteria. However, the activated neutrophil may also damage normal tissue and participate in diseases such as rheumatoid arthritis and the adult respiratory distress syndrome (ARDS). | |
| 2442110 | Purified podophyllotoxin (CPH-86) inhibits lymphocyte proliferation but augments macrophag | 1987 | Purified podophyllotoxin (CPH-86) is an inhibitor of microtubular aggregation used in the treatment of cancer, psoriasis and rheumatoid arthritis. To better understand its immunopharmacology we examined its effects on human lymphocytes and monocytes and guinea pig macrophages. CPH-86 inhibits mitogen-induced human lymphocyte proliferation and macrophage growth factor-stimulated macrophage proliferation with ID50s of approximately 10(-7) M. The effect of CPH-86 on lymphocytes in conjunction with mitogen is nonlethal, evident during the early but not the late phases of proliferation, and associated with early increases in cyclic AMP levels. In contrast to these obviously inhibitory effects, CPH-86 (10(-7) M) alone induces IL-1 by human monocytes and, with mitogen, it induces IL-2 production by human lymphocytes. It directly stimulates macrophage proliferation and potentiates the effects of low doses of macrophage growth factor to do so. The latter effects may be mediated by colony stimulating factor production. The effects of CPH-86 are not mediated by inhibition of prostaglandin synthesis. The stimulation of monokine and lymphokine production by CPH-86 may represent positive features of its action and may be immunotherapeutic. | |
| 3316257 | Immunological mediators of wound healing and fibrosis. | 1987 | T-lymphocytes, monocytes, and macrophages, which are the central constituents of immunological and chronic inflammatory reactions, generate numerous polypeptides and other factors capable of stimulating and modulating the proliferation and functions of fibroblasts. These principles differ widely in structure, target cell preference, and functional specificity. The involvement of immunological mediators of fibroblast activities in normal wound healing has not been defined, but a role in some chronic fibrosing disorders, including rheumatoid arthritis, has been suggested by the findings of functionally relevant concentrations in affected tissues. The elucidation of both the pathways of production of fibroblast-activating factors (FAFs) and the determinants of fibroblast responses will permit new approaches to the diagnosis and treatment of deficiencies in wound healing and of abnormal fibrosis. | |
| 2159393 | Axonal polyneuropathy without vasculitis, follicular lymphoma and primitive sicca syndrome | 1990 Mar | A woman suffering from primary Sjögren's syndrome developed sensitive neuropathy. The disease was further complicated by follicular lymphoma, an unusual albeit already described complication of Sjögren's disease. The clinical data suggest that mononuclear infiltration of the dorsal root ganglions could be at the origin of a sensitive neuropathy, inducing an axonal degeneration of the nerves. | |
| 2302267 | c-myc proto-oncogene expression in peripheral blood mononuclear cells from patients with p | 1990 Jan | We examined peripheral blood mononuclear cells (PBMC) from 16 patients with Sjögren's syndrome (SS) and 7 normal control subjects for the expression of the c-myc proto-oncogene. Patients with SS were found to have a significantly increased expression of c-myc messenger RNA compared with normal individuals. No abnormal forms of c-myc RNA were detected in the SS patients. DNA analysis did not show deletion, rearrangement, or amplification in the c-myc proto-oncogene. The methylation status of the c-myc gene in patients with SS was found to be comparable with that of the control subjects. Nuclear run-off assays showed increased transcription of the c-myc gene in some patients but normal transcription in others, suggesting that posttranscriptional mechanisms are also involved in the increased c-myc messenger RNA observed in these patients. Two patients with primary SS and B cell lymphomas were found to have normal c-myc expression in their PBMC. These results demonstrate the presence of activated PBMC in patients with primary SS and delineate some of the mechanisms that are involved at the molecular level. We speculate that increased c-myc expression may represent an early permissive event in the progression toward neoplasia in these patients. | |
| 2789073 | Anti-SL-Ki antibody in a patient with fatal connective tissue overlap disease. | 1989 Aug | A patient with photosensitivity is described who presented with an overlap syndrome combining features of systemic lupus erythematosus with a mild polymyositis and scleroderma and with symptoms of the sicca syndrome. In addition, he was anti-SSA/Ro positive and had a constellation of antibodies directed to ENA including the anti-SL-Ki antibody. The condition was fatal and he died from heart failure and respiratory insufficiency. | |
| 3141095 | Monoclonal immunoglobulins in the serum of patients with primary Sjögren's syndrome. | 1988 Jul | Monoclonal immunoglobulins (M Igl) were detected in the serum of 10 of 20 patients with primary Sjögren's syndrome (prim. SS), by using high resolution electrophoretic technique combined with immunofixation. The finding of three free lambda chains and two IgG lambda suggests that the lambda-expressing B-clones are involved in this process, but the class distribution is different from one series to another, and from one country to another. The prim. SS patients with multiogran disease have the higher incidence of M Igl. | |
| 3259986 | The effect of age on clinical and serological manifestations in unselected patients with s | 1988 Mar | In a unique series of 80 patients with systemic lupus erythematosus constituting all identified cases in a defined population, the effect of age, at onset and at diagnosis, on disease expression was examined. Contrary to current views, the incidence of the disease was similar among all age groups. The proportion of patients with serositis, secondary Sjögren's syndrome, and anti-SSA antibodies gradually increased with age, while that of cutaneous symptoms, antibodies to native DNA, and hypocomplementemia decreased. Serositis was common as the initial symptom in the elderly and serositis or musculoskeletal manifestations were the initial symptom in 88% of patients over 50 at onset of disease. |