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ID PMID Title PublicationDate abstract
9973520 Cross-linking of CD44 on rheumatoid synovial cells up-regulates VCAM-1. 1999 Feb 15 CD44 is a ubiquitous molecule also known as hyaluronic acid or homing receptor. However, the cellular functions and its role in inflammation, for example, rheumatoid synovitis, are currently unknown. In this study, we propose a novel function for CD44. Using synovial cells from rheumatoid arthritis (RA) patients, we demonstrated that CD44 cross-linking and binding to hyaluronan augmented VCAM-1 expression and subsequently VCAM-1-mediated cell adhesion. Briefly, we found that 1) rheumatoid synovial cells highly expressed CD44; 2) cross-linking of CD44 markedly but transiently augmented VCAM-1 expression and its mRNA transcription much more than did IL-1beta and TNF-alpha; 3) hyaluronan, especially when fragmented, also up-regulated VCAM-1; 4) CD44 activated the transcription factor AP-1; and 5) the integrin-dependent adhesive function of RA synovial cells to T cells was also amplified by CD44 cross-linking. These results indicate that the adhesion of RA synovial cells to matrices such as hyaluronic acid through CD44 could up-regulate VCAM-1 expression and VCAM-1-mediated adhesion to T cells, which might in turn cause activation of T cells and synovial cells in RA synovitis. We therefore propose that such cross-talking among distinct adhesion molecules may be involved in the pathogenesis of inflammation, including RA synovitis.
11602473 Work factors and behavioural coping in relation to withdrawal from the labour force in pat 2001 Nov OBJECTIVE: To assess separate and combined effects of work factors and behavioural coping in relation to withdrawal from the labour force among patients with rheumatoid arthritis (RA). METHODS: A cross sectional study was conducted in a Dutch nationwide random sample of 720 patients with RA. Information about work factors and behavioural coping was collected by a self-administered postal questionnaire. A broad variety of work factors and coping styles were evaluated separately and in combination using multivariate logistic regression analyses, controlling for sociodemographic and disease related variables. Attributable and preventable fractions were calculated from the combined analyses to assess the relative importance of the contributing factors. RESULTS: Additional job training, equal career opportunities, letting the disease influence the choice of the current job position, and informing colleagues about having the disease were negatively associated with withdrawal from the labour force. The most relevant factor in terms of decreasing the risk was adjusting job demands which accounted for 63% of the patients still in the labour force. Decreasing activities and diverting attention in order to cope with pain, and pacing in order to cope with limitations were the coping styles which were positively associated with withdrawal from the labour force. The most relevant factor in terms of increasing the risk of withdrawal was pacing which accounted for 67% of the withdrawals. CONCLUSION: Work factors are potentially important modifiable risk factors for withdrawal from the labour force in patients with RA. Behavioural coping is also relevant.
10083957 Pain in the rheumatic diseases. Practical aspects of diagnosis and treatment. 1999 Feb Patients with rheumatic disease experience pain that can be intense, persistent, and disabling. This pain is frequently multifactorial in origin and has both central and peripheral components. Because of the array of conditions that can cause musculoskeletal pain, patient management must begin with a complete clinical assessment that identifies possible etiologies and measures objective findings against subjective complaints. Especially in patients with known rheumatic disease, the possibility of concurrent pain of central origin must be considered and appropriate treatment given. By applying a comprehensive therapy plan of drugs, physical therapy, and patient education, significant benefits can often be achieved in this prevalent group of painful diseases.
10540171 Tumour necrosis factor (TNF) production by T cell receptor-primed T lymphocytes is a targe 1999 Oct Methotrexate (MTX) is an effective immunosuppressive agent in various chronic inflammatory diseases such as rheumatoid arthritis (RA). However, its mechanisms of action are only partially understood. In this study, we assessed the effects of MTX on the differentiation of peripheral blood (PB) CD4+CD45RA 'naive' and CD4+CD45RO 'memory' T cells from healthy controls and patients with RA. Accordingly, purified T cells were primed and restimulated in vitro via the T cell receptor (TCR) in the presence of IL-2 to generate effector T cells secreting large amounts of Th1 and Th2 cytokines. We observed that low doses of MTX strongly suppress TNF and to a lesser extent interferon-gamma (IFN-gamma) production by T cells from both healthy donors and RA patients when present during T cell priming via the TCR. Similar data were obtained for TCR-primed synovial fluid mononuclear cells in RA. In contrast, production of IL-4 by TCR-primed CD45RA T cells was significantly increased upon MTX treatment. Interestingly, MTX did not enhance IL-4 production when present during restimulation of effector CD45RO T cells, although it still suppressed TNF production. The results indicate that MTX effects depend on the stage of T cell activation and identify TNF production by TCR-primed T lymphocytes as a target for low-dose MTX treatment in RA. These findings could explain the delayed clinical effects of MTX and may contribute to its potent anti-inflammatory and immunoregulatory properties.
11028836 The use of 5-HT3 receptor antagonists in various rheumatic diseases--a clue to the mechani 2000 In a pilot study, the action of the 5-HT3 receptor antagonist, tropisetron, on different types of local rheumatic pain and inflammatory effects was studied. With intra-articular injection of tropisetron, an improvement in inflammation and pain was obtained in inflammatory rheumatic diseases and activated osteoarthrosis. Also, the majority of patients with localized soft-tissue rheumatic diseases (periarthritis) demonstrated an obvious decrease in their pain following local infiltration of tropisetron. Chronic low back pain and cervical pain responded somewhat to i.v. treatment with tropisetron. The effect of the 5-HT3 receptor antagonists is probable primarily to limit the release of substance P, which acts as a pain and inflammatory mediator, and is itself released by the neurogenic inflammation that occurs after the binding of serotonin to its corresponding receptor. These results should be backed up with placebo controlled studies, which if confirmed, might imply that 5-HT3 receptor antagonists could supplement or replace the local administration of corticosteroids.
9605178 Serum amyloid A protein induces production of matrix metalloproteinases by human synovial 1998 May Serum amyloid A (SAA) is a precursor protein for amyloid A, which is a constituent for amyloid fibrils in secondary amyloidosis. To determine the role of SAA in the articular destruction in patients with rheumatoid arthritis (RA), we investigated the effects of SAA on the production of matrix metalloproteinases (MMPs) by rheumatoid synovial fibroblasts. SAA stimulated rheumatoid synovial fibroblasts to produce MMP-2 and MMP-3 in a dose-dependent manner. Pretreatment of synovial fibroblasts with cycloheximide prevented SAA-mediated MMP-2 and MMP-3 secretion. When SAA-containing media were immunodepleted by anti-SAA-specific antibody, SAA-mediated MMP secretion was also abrogated. The level of MMP-3 mRNA was increased in SAA-stimulated synovial fibroblasts compared with that of control cells. Our data indicate that SAA is a potent inducer of MMPs in the RA synovium and may play a critical role in the degradation of extracellular matrix in the rheumatoid joint.
9374926 Predisposing factors in sulphasalazine-induced systemic lupus erythematosus. 1997 Oct The aim of this study was to define predisposing factors in patients with sulphasalazine-induced systemic lupus erythematosus (SLE). Eleven patients with onset of SLE or SLE-like syndromes during sulphasalazine treatment are reported. Before the onset of SLE, five of the patients suffered from rheumatoid arthritis (RA), one from psoriatic arthropathy (PsoA), two from juvenile chronic arthritis (JCA) and three from ulcerative colitis (UC). At the time of diagnosis of drug-induced SLE, analysis of antinuclear antibodies (ANA), anti-double-stranded DNA antibodies (anti-dsDNA), anti-histone antibodies (anti-histones), acetylator status of the enzyme N-acetyltransferase 2 (NAT2) and HLA classification were performed. All patients were anti-DNA positive at disease onset and were determined to be slow acetylators. HLA A1 occurred in 4/10 patients, B8 in 5/10. HLA DR 3 was represented in one patient and DR 3(17) in five patients. The DQA1* 0501 allele was observed in 7/10 patients and DQB1 0201* in 6/10. Persistent SLE and development of nephritis were noted in patients with long duration of treatment and high cumulative dose of sulphasalazine (> 1000 g). In sulphasalazine-induced SLE, slow acetylator genotype and HLA haplotypes associated with idiopathic SLE seem to predict disease induction. Further, as the risk of developing persistent SLE and nephritis increases with long-standing sulphasalazine medication, it is of importance to monitor the patients with regard to signs of SLE during the entire treatment period.
11315923 Implication of cartilage intermediate layer protein in cartilage destruction in subsets of 2001 Apr OBJECTIVE: To investigate whether cartilage intermediate layer protein (CILP), a protein recently cloned from human articular cartilage, is recognized as an autoantigen in patients with osteoarthritis (OA) and rheumatoid arthritis (RA), and whether the immune response against CILP is involved in disease pathogenesis. METHODS: Recombinant fusion proteins, which contain the first half (C1), second half (C2), or 3 fragments within the C2 region (designated C2F1, C2F2, and C2F3) of the non-porcine nucleotide pyrophosphohydrolase-homologous region of CILP, were prepared using Escherichia coli. Autoantibodies to these proteins in serum samples from patients with OA or RA and from age-matched healthy individuals were detected by enzyme-linked immunosorbent assay and Western blotting. In addition, mice were immunized with a mixture of the C1 and C2 fusion proteins to assess the arthrogenicity of CILP. RESULTS: Production of antibodies to the C2 region was detected in 10.5% (11 of 105) of the tested OA patients and in 8.0% (7 of 88) of the tested RA patients, although antibodies to the C1 region were rarely detected in either patient group. All C2F1, C2F2, and C2F3 fragments were found to carry autoepitopes. The C2F2 fusion protein was recognized most frequently in the tested OA patients, whereas the C2F3 fusion protein was dominantly recognized in the tested RA patients. All 4 mice strains, DBA/1J, ICR, C57BL/6, and BALB/c, immunized with the CILP fusion proteins developed chronic arthritis; in particular, the ICR mice developed polyarthritis that was characterized by infiltration of mononuclear cells in the synovium and exfoliation of the surface of cartilage. CONCLUSION: The immune response to CILP may play a role in the pathogenesis of inflammatory joint destruction. Our results support the role of an immune-mediated process in the joint destruction present in chronic arthropathies such as OA and RA. The results suggest that suppression of immune responses to various components of the cartilage, such as CILP, might be therapeutically beneficial in these chronic arthropathies.
9268806 A new method of treatment for periprosthetic supracondylar fractures of the femur for pros 1997 Aug Knee arthroplasty periprosthetic supracondylar fracture of the femur is a well-recognized problem that is likely to be seen more frequently with the increasing number of knee arthroplasties being performed. Treatment of this fracture is difficult. A new method of internal fixation for supracondylar fractures around a stemmed femoral component using a custom-made extension to the femoral stem is described. This technique allowed early mobilization of the patient, with restoration of a good range of movement of the knee and fracture union within 1 year.
10371285 Porphyria cutanea tarda affecting a rheumatoid arthritis patient treated with methotrexate 1999 May We describe the case of a 44-yr-old woman, suffering from rheumatoid arthritis for 15 yr, who developed porphyria cutanea tarda while being treated with methotrexate. The cutaneous lesions healed and the metabolic anomalies improved after a few months, despite continuing the treatment.
11550025 Comparative study of catalytic (DNA-hydrolyzing) and cytotoxic properties of anti-dna auto 2001 Apr DNA-hydrolyzing and cytotoxic properties of anti-DNA autoantibodies isolated from patients with systemic autoimmune diseases and from autoimmune MRL-lpr/lpr, SJL/J, and (NZBx NZW)F1 mice were studied. Cytotoxic and catalytic properties of these antibodies correlated. A relationship between the stage of systemic lupus erythematosus and catalytic and cytotoxic properties of DNA abzymes was revealed. Of all studied cells, L929 cells were most sensitive were most sensitive to in vitro effect of antibodies. Treatment of target cells with anti-DNA autoantibodies with cytotoxic properties induced internucleosomal DNA fragmentation, which is characteristic of apoptosis.
11446439 Effect of pre-loading oral glucosamine HCl/chondroitin sulfate/manganese ascorbate combina 2001 Feb The therapeutic effect of a nutritional supplement consisting of a combination of glucosamine hydrochloride (FCHG49), purified sodium chondroitin sulfate (TRH122), and manganese ascorbate (GCM)3 was investigated in the rat model of collagen-induced autoimmune arthritis (CIA). The GCM compound was mixed with a palatable nutritional paste (Nutri-cal [NC]). Oral administration of the NC/GCM compound was initiated in 26 rats 10 days before immunization and continued until the day of sacrifice. One group of 12 control rats was given no oral agents; a second group of 12 control rats received NC only. Evaluations included arthritis index (AI) scoring by three independent evaluators, histologic index (HI) scoring of lesions, T-cell proliferation, and serological studies for antibody classes and subclasses. Both the AI and HI criteria showed a statistically significant reduction in the prevalence of CIA in rats pretreated with the NC/GCM (54%) compared to the combined control groups (96%, chi2 analysis P = 0.001). Rats fed the NC/GCM also exhibited a significant decrease in the severity of autoimmune arthritis in both the AI and HI compared to control Group 2 (immunized-NC) (chi2 analysis P < 0.05). Histological studies verified the decreased incidence of arthritis in the NC/GCM group compared to control Group 2. GCM treatment failed to alter T-cell proliferation and antibody production to bovine type-II collagen, indicating that its effects are not due to alteration of the antigen-specific immune response.
9330940 Taking baths: the efficacy of balneotherapy in patients with arthritis. A systematic revie 1997 Oct OBJECTIVE: To review English, French, German, and Dutch language studies of the effectiveness of balneotherapy. Balneotherapy (hydrotherapy or spa therapy) is one of the oldest forms of therapy for patients with arthritis. One of the aims of balneotherapy is to relieve pain. METHODS: We performed a systematic review that included randomized and nonrandomized studies. Quality scores of the studies were determined using a criteria list. RESULTS: Most studies report positive findings, but all studies showed methodological flaws. A quality of life measurement was never reported as an outcome measure. None of the randomized clinical trials included intention-to-treat analysis or comparison of effects between groups. CONCLUSION: Because of the methodological flaws a conclusion about the efficacy of balneotherapy cannot be provided from studies we reviewed. We conclude that most flaws found could be avoidable in future research.
10392665 Lymphoma in patients with rheumatoid arthritis: what is the evidence of a link with methot 1999 Jun An increasing number of instances of lymphoma in patients with rheumatoid arthritis who are treated with methotrexate continue to appear. The majority of patients with lymphoproliferation have features of immunosuppression-associated lymphoma. Rheumatoid arthritis itself and the actions of methotrexate concur in leading to a immunosuppressed state. Possible oncogenic mechanisms and the risk factors for patients with rheumatoid arthritis to develop lymphoma while receiving methotrexate include: (i) intense immunosuppression and severe disease in combination with genetic predisposition and; (ii) an increased frequency of latent infection with prooncogenic viruses like Epstein-Barr virus. The aetiological role of methotrexate in the development of these lymphomas is supported by the spontaneous remission of these malignancies in some of patients with rheumatoid arthritis after methotrexate has been stopped. The physicians caring for patients with rheumatoid arthritis receiving methotrexate should be vigilant about signs and symptoms suggestive of lymphoma, mostly in those patients with significant comorbidity, long standing and severe disease who are more likely to be immunosuppressed. If a lymphoma appears in these patients, methotrexate should be stopped. Spontaneous remission may occur and a period of observation is advisable when clinically possible. If functional deterioration appears or there are signs of lymphoproliferative organ invasion after several months then specific antineoplastic treatment should be instituted.
10323452 Human interleukin-17: A T cell-derived proinflammatory cytokine produced by the rheumatoid 1999 May OBJECTIVE: To investigate the presence and role of interleukin-17 (IL-17) in rheumatoid arthritis (RA), and its regulation by antiinflammatory cytokines. METHODS: The production of IL-17 was measured in supernatants of RA, osteoarthritis (OA), and normal synovial tissue pieces cultured ex vivo. Quantification of IL-17 was performed using a specific biologic assay. IL-17 gene expression was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR)-techniques. Immunohistochemistry was used to evaluate the frequency of IL-17-positive cells in synovium. The secretion of IL-17 by synovium was measured in the presence of IL-4, IL-13, and IL-10. In addition, the contributions of exogenous and endogenous IL-17 to IL-6 production by RA synovium were studied. RESULTS: Functional IL-17 was spontaneously produced by 16 of 18 RA (mean +/- SEM 41.7+/-11.4 units/ml), 2 of 12 OA (5.3+/-4.5 units/ml), and 0 of 3 normal synovial explant cultures. IL-17 messenger RNA expression was demonstrated by RT-PCR in 4 of 5 RA and 0 of 3 OA synovial samples. By immunostaining of RA synovium, IL-17-producing cells were found in the T cell-rich area. Addition of both IL-4 and IL-13 completely inhibited the production of IL-17, whereas IL-10 had no effect. Addition of exogenous IL-17 to RA synovium resulted in an increase in IL-6 production, whereas that of a blocking anti-IL-17 antibody reduced production of IL-6. CONCLUSION: The T cell cytokine IL-17 was found to be highly produced by RA, but not by OA, synovium. Its production and function were down-regulated by IL-4 and IL-13. These results indicate that IL-17 contributes to the active, proinflammatory pattern that is characteristic of RA. Through the contribution of IL-17, some Th1-like T cells appear to mediate synovial inflammation.
10464556 Disease modifying and immunomodulatory effects of high dose 1 alpha (OH) D3 in rheumatoid 1999 Jul OBJECTIVE: Vitamin D analogues such as 1 alpha (OH) D3 (alphacalcidiol) have a possible physiological paracrine effect on cell proliferation and differentiation. Experimentally established possibilities to prevent autoimmune diseases suggest that alphacalcidiol may have therapeutic value as an immunomodulatory agent in patients with rheumatoid arthritis. METHODS: We organized a 3-month open-label trial on 19 patients being treated with standard DMARD therapy for acute RA. They were divided into 2 subgroups, those with highly active RA and those with moderately active RA. Their regular drug regimen was maintained during the trial and oral alphacalcidiol 2 micrograms/day was added. Therapy results were evaluated by ESR, CRP, morning stiffness, the Richie index, and the Lee index. Immunomodulatory effects were investigated by measuring lymphocyte proliferation and apoptosis both in the patients and in vitro in 10 nM alphacalcidiol-supplemented culture medium. RESULTS: After 3 months, high dose oral alphacalcidiol therapy showed a positive effect on disease activity in 89% of the patients (45% or 9 pts. with complete remission and 44% or 8 pts. with a satisfactory effect). Only two patients (11%) showed no improvement, but no new symptoms occurred. No side effects were observed. CONCLUSION: These results suggest that alphacalcidiol is a powerful immunomodulatory agent with fairly low hypercalcemic activity. Clinical improvement was strongly correlated with the immunomodulating potential of this agent. We noticed dual effects on lymphocyte proliferation and apoptosis according to the prior cell activation state. Alphacalcidiol could therefore possibly be used as an adjunct therapy with DMARDs in patients with rheumatoid arthritis.
11508586 Comparison of extracapsular changes by magnetic resonance imaging in patients with rheumat 2001 Aug OBJECTIVE: Joint inflammation in polymyalgia rheumatica is regarded primarily as a disease of the synovial cavities and bursae, but the adjacent capsules and soft tissues have not been evaluated using sensitive imaging methods. We used fat suppression magnetic resonance imaging (MRI) to determine anatomical sites of inflammatory change in the shoulders of patients with early polymyalgia rheumatica (PMR) and a control group of patients with rheumatoid arthritis (RA). METHODS: Fourteen patients with PMR and 14 with RA (a total of 20 shoulders in each group) were evaluated. T2 SPIR (fat suppressed) coronal oblique MRI sequences of the shoulders were performed. Scans were assessed for sites of joint effusion, bursitis, tenosynovitis, bone edema, and extracapsular soft tissue edema. Statistical analysis was performed using Fisher's test. RESULTS: Nine of 14 patients (10/20 joints) with PMR but only 2/14 (2/20 joints) with RA had prominent edema at extracapsular sites adjacent to the joint capsule or in the soft tissues (p = 0.02). Both groups had a comparable degree of joint effusion (18 PMR, 17 RA), bursitis (18 PMR, 16 RA), and tenosynovitis (3 PMR, 2 RA). CONCLUSION: The only significant difference between the 2 groups was the presence of inflammatory change outside the joint cavity in patients with PMR. This may contribute to the diffuse nature of symptoms in PMR and have implications for its pathogenesis.
11387587 A validation of the 10-meter incremental shuttle walk test as a measure of aerobic power i 2001 Jun OBJECTIVE: To validate a simple, clinically relevant, and inexpensive test of aerobic power-the 10-meter incremental shuttle walk test (SWT)--in 2 separate patient populations. DESIGN: Two-sample validity study. SETTING: Physiotherapy department of major hospital in the United Kingdom. PATIENTS: Convenience samples of rheumatoid arthritis (RA) patients (n = 10) and cardiac patients (n = 10). INTERVENTION: Subjects were attached to a portable respiratory gas analyzer to measure oxygen uptake. They walked around an oval 10-meter course, starting at 0.5m/s, with velocity gradually increased by .17m/s increments for as long as they could, for up to 12 minutes. MAIN OUTCOME MEASURES: A subject's maximal rate of oxygen uptake during exercise (V(O)(2)max) established with linear extrapolation was regressed against the number of shuttles completed (distance walked). An earlier study (n = 28) showed high levels of reliability and validity with linear extrapolation. RESULTS: No significant linear relationship was found between V(O)(2)max and the number of shuttles completed (R(2); RA subjects = 9.7%, cardiac subjects = .03%, p > .05). CONCLUSION: These results do not support use of the SWT as a representative measure of aerobic power. Despite this finding, the advantages of developing a clinically viable alternative to costly laboratory testing warrants further study of the SWT in patient groups.
11011110 An evidence-based approach to prescribing NSAIDs in the treatment of osteoarthritis and rh 2000 Autumn The Second Canadian Consensus Conference was convened to discuss the latest developments in the management of osteoarthritis (OA) and rheumatoid arthritis (RA), and to make evidence-based recommendations, specifically regarding the use of nonsteroidal anti-inflammatory drugs (NSAIDs) for these indications in primary care practice. The recent availability of cyclo-oxygenase-2-specific inhibitors has raised questions as to their role in the pharmacological management of OA and RA, particularly in relation to conventional treatments such as acetaminophen and nonspecific NSAIDs (with or without misoprostol or proton pump inhibitors). The recommendations in this document, which were arrived at through critical review of data from published randomized, clinical trials, deal with treatments of choice, information to discuss with patients, use of NSAIDs in patients at risk for serious upper gastrointestinal complications, renal or hepatic impairment or congestive heart failure, appropriate follow-up, and the use of NSAIDs with anti- hypertensives, warfarin, low dose acetylsalicylic acid and other medications. The goal of these recommendations is to improve patient outcomes in the primary care setting by maximizing treatment efficacy and minimizing rates of adverse events.
10743803 Effects of sulfasalazine and its metabolites on steady state messenger RNA concentrations 2000 Mar OBJECTIVE: To determine the effects of sulfasalazine (SASP) and its metabolites sulfapyridine (SP) and 5-amino salicylic acid (5ASA) on steady state mRNA levels of inflammatory cytokines [interleukin 1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha)], matrix metalloproteinases [collagenase (MMP1), stromelysin (MMP3), gelatinase 72 kDa (MMP2)], tissue inhibitors of metalloproteinase (TIMP 1 and TIMP 2), and the TNF-alpha receptor in rheumatoid synovial fibroblasts. METHODS: Cells were dosed with each compound for 24 h in the presence or absence of PMA inducer and messenger RNA (mRNA) extracted and subjected to Northern blot analysis. Messenger RNA levels were quantitated by densitometry and normalized to GAPDH or 18S rRNA. RESULTS: We observed some modest effects of sulfasalazine and its metabolites on steady state mRNA levels including: (1) repressed mRNA levels for TNF-alpha [approximately 40% with 3x (drug median serum concentration) all 3 drugs], stromelysin (approximately 24% with 3x all 3 drugs and approximately 31% with 3x 5ASA), and collagenase (approximately 27% with 3x 5ASA); (2) elevated mRNA levels for TIMP 2 (3.5 kb transcript) (51% with 3x SP and 44% with 3x 5ASA), gelatinase (approximately 20% with 3x SP and 3x 5ASA), stromelysin (approximately 40% with 3x and 1x SASP), IL-1beta (approximately 31% with 0.1x 5ASA); and (3) no effect on mRNA levels for TNF-alpha receptor and TIMP 1. CONCLUSION: (1) SASP and its metabolites showed varied effects on steady state mRNA concentrations for gene transcripts that fell into 3 categories: (a) repressed, (b) elevated, (c) no effect on mRNA levels. (2) No apparent linear dose response effect was observed for SASP or its metabolites, although a generalized suppression of mRNA levels at all doses was seen in some cases. (3) No predominant suppressive effect (> or = 50%) of mRNA levels by any of the drugs was observed for any of the genes studied; however, TIMP 2 mRNA levels increased 51% with 3x SP and 44% with 3x 5ASA.