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ID PMID Title PublicationDate abstract
9575391 Self-reported coping behavior in health and disease: assessment with a card sort game. 1998 Spring The authors tested the hypothesis that individuals with a variety of severe chronic illnesses and the healthy elderly exhibit a loss of flexibility in their response to a variety of stressors, compared with healthy adults. A card sort game designed to assess self-reported coping behavior under different stressful life situations was used to compare healthy adults with individuals with multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and the elderly. The healthy adults were found to exhibit more variability than any of the illness groups or the elderly. Healthy function is marked by a complex type of variability.
11064600 [Interference in turbidimetric immunoassay for serum C-reactive protein due to serum prote 2000 Aug Interference in immunoassays for CRP caused by serum protein abnormalities was studied with special reference to turbidimetric immunoassay(TIA) and latex photometric immunoassay(LPIA). One of the interfering factors in TIA is immune complex or agglutinating immunoglobulin which reacts with a chemical component like polyethylene glycol in reagent of the first reaction and causes remarkable turbidity in the initial phase. Since the turbidity decreases gradually and can not be eliminated within the first reaction, the second reaction is affected by the continuing reduction in absorbance, resulting in falsely low CRP values. As examples of this kind of interference, two cases, case 1 and 2 were presented. Case 1 involved malignant lymphoma with paraproteinemia of monoclonal IgA(kappa) and Case 2 was chronic viral hepatitis type C with type II cryoglobulinemia composed of monoclonal IgM(kappa) and polyclonal IgG. Rheumatoid factor(RF) is another factor that interferes in TIA which reacts with antibody in the reagent of the second reaction and causes falsely high CRP values. The effect of RF is especially remarkable in LPIA. As an example, a case of chronic rheumatoid arthritis(Case 3) with polyclonal IgM is presented. Predilution of serum(5-fold dilution with physiological saline solution) was proved to be effective in reducing the intensity of interference in TIA caused by immune complex or agglutinating immunoglobulin in Cases 1 and 2. Covalent binding of IgG(Fab')2 to latex particle instead of physical adsorption of IgG was shown to be efficient in eliminating interference caused by RF in LPIA in Case 3.
9492569 [Remission induction after pentoxifylline treatment in a patient with rheumatoid arthritis 1997 Dec Pentoxifylline (POF) has been shown to have anti-inflammatory and immunomodulatory effects. including suppression of TNF-alpha production by activated macrophages, Th-1 response of T cells, and fibroblasts' proliferation and metalloproteinase production. Pentoxifylline was also reported to possess therapeutic properties in 50% of severe refractory RA in an open study. We experienced a 64 year-old man with seronegative RA, stage 2, class 3. He showed 23 swollen joints, 32 painful joints, ADL score 37/40, and ESR 135 mm/h. All these parameters were dramatically improved 3 weeks after administration of POF 300 mg/d and prednisolone 5 mg/d. Discontinuation of POF resulted in rapid exacerbation of RA. POF was restarted and the patient showed complete recovery from arthritis with normalization of ESR within 3 months and was maintained a complete remission for another 1 year. This case further supports a potential antirheumatic effect of POF on some patients with RA.
9722924 Modulation of disease by superantigens. 1998 Aug Increasing evidence suggests that bacterial and viral superantigens are involved in immune-mediated disease. Studies using an animal model for multiple sclerosis show that superantigens can induce relapses and bring into play autoreactive T cells with restricted usage of T cell receptor V beta families that may be indirectly involved in the initial episode of disease. This may also involve epitope spreading. Superantigens have also been implicated in other autoimmune diseases such as rheumatoid arthritis and psoriasis. Superantigens encoded by viruses such as mouse mammary tumor virus play an important role in disease progression.
10907353 [Glucocorticosteroid induced osteoporosis in patients with rheumatoid arthritis]. 2000 Glucocorticosteroids have been recognized as a well known risk factor for drug induced osteoporosis. Many studies have shown a decrease in bone mass, bone quality disorders and an increase in the risk of fractures in patients with long-term corticosteroid therapy. Rheumatic patients, particular with rheumatoid arthritis, who are usually chronic steroid users are at the highest risk. On the other hand uncontrolled active inflammatory process is also a main factor for rapid bone loss. Some studies suggest that patients with low dose corticosteroid therapy (prednisone 5 to 7.5 mg per day) are not at increased risk of osteoporosis. Our study of 36 rheumatoid arthritis women treated with daily prednisone doses between 5 to 7.5 mg in comparison with non-steroid control group confirmed the above suggestion.
11263011 [Are there effective dietary recommendations for patients with rheumatoid arthritis?]. 2001 Feb Patients with rheumatic diseases frequently ask the physician for diet recommendations. Although much has been written about this subject, scientifically validated studies investigating the impact of certain diets on rheumatoid arthritis are scant and often inconclusive. Elimination diets or total fasting is believed to eliminate food ingredients that cause or aggravate arthritis. In contrast, supplementation with fish oil, gamma-linoleic acid or vitamin E is directed at anti-oxidative and anti-inflammatory effects of these food compounds. So far, both approaches have failed to reveal a significant benefit with respect to objective signs of inflammation. Supplementation with other vitamins such as vitamin A and C, or with trace elements like selenium and zinc are of no proven influence on the disease activity as well. There is a higher request for calcium and vitamin D in patients with active RA under steroid treatment to prevent osteoporosis. In addition, patients with active RA have a slightly increased risk for cardiovascular events. Therefore, cholesterol-lowering diets and drugs should be applied early.
9779853 Psychometric evaluation of a Korean Health Assessment Questionnaire for clinical research. 1998 Oct OBJECTIVE: The Health Assessment Questionnaire (HAQ) is a widely used, easily administered functional scale that has high reliability and validity. Although translated versions of HAQ are available, no Korean version exists. Our aim was to translate and confirm the reliability and validity of a Korean language version of the HAQ. METHODS: HAQ was translated into Korean by 3 translators and translated back into English by 3 different translators. Four questions were modified for the Korean culture. Fifty-six consecutive patients with RA were asked to rate the comprehensibility of the questions on a 4 point scale. The comprehensibility (responding with "3 or above") ranged from 76 to 98%. Another 60 consecutive patients with RA were studied for the psychometric properties of the Korean version. RESULTS: The test-retest reliability of the Korean HAQ (KHAQ) yielded an intraclass correlation coefficient of 0.99. The Cronbach standardized alpha was 0.95 among 20 items. For construct validity, the correlation of KHAQ scores with disease severity [tender joint count, swollen joint count, patient's self-assessment of pain, erythrocyte sedimentation rate (ESR), Ritchie Index] was high and statistically significant, except for ESR. The 4 revised items were appropriate expressions of physical function since the correlations between each of the revised items and the first principal component are similar in magnitude to those between the 16 unchanged items and the principal component. CONCLUSION: The reliability and validity of the KHAQ is confirmed. The evaluation of responsiveness of the KHAQ is in progress.
10943856 Multipoint linkage analysis of a candidate gene locus in rheumatoid arthritis demonstrates 2000 Aug OBJECTIVE: Rheumatoid arthritis (RA) is the most common disabling autoimmune disease, affecting approximately 1% of the population. The disease etiology is unknown, but it involves inflammation and immune dysregulation and is influenced by genetic variation at both HLA and other, as-yet-unidentified genetic loci. Corticotropin-releasing hormone (CRH; or corticotropin-releasing factor), a primary regulator of the hypothalamic-pituitary-adrenal axis and a key element in the response to stress and inflammation, is a strong candidate gene for RA. We examined the role of DNA variation across the region containing this gene in multicase families with RA. METHODS: We genotyped fluorescently labeled simple tandem repeat genetic markers from chromosome 8q13 in 295 families with multiple cases of RA. Singlepoint and multipoint nonparametric linkage analysis and association analysis using transmission disequilibrium testing (TDT) were also used. RESULTS: Single-point linkage analysis using a microsatellite within 30 kb of the CRH locus (CRH.PCR at position 8q13) showed a significant excess of allele sharing in 295 United Kingdom RA families with at least 2 affected members (MapMaker/Sibs logarithm of odds [LOD] 1.4; P = 5.5x10(-3); mean identity by descent [ibd] sharing 55.9%). To provide a more detailed linkage map, a multipoint analysis was conducted with an additional 7 dinucleotide microsatellite markers (average heterozygosity 0.75) flanking the CRH locus. Significant linkage was detected over a 22-cM region between D8S285 and D8S530, with the maximum singlepoint LOD score of 1.77 at D8S1723 (MapMaker/Sibs P = 2.2x10(-3); mean ibd sharing 59.3%). Multipoint analysis showed strongest evidence for linkage at the same marker (multipoint LOD 1.78, P = 2.1x10(-3), mean ibd sharing 55.8%). TDT analysis showed significant association at the CRH locus (P = 2.6x10(-3)). CRH has a sibling relative risk of 1.14, and contributes <10% to the sibling relative risk of RA. CONCLUSION: With the exception of HLA, this is the strongest evidence yet of a genetic locus that is both linked to and associated with RA, and provides an avenue for further genetic characterization and potentially novel therapeutic intervention.
11472439 Selective recruitment of CCR6-expressing cells by increased production of MIP-3 alpha in r 2001 Jul Infiltration of various types of leucocytes has been shown to play a crucial role in the pathogenesis of rheumatoid arthritis (RA). Macrophage inflammatory protein-3 alpha (MIP-3 alpha) is a recently identified chemokine which is a selective chemoattractant for leucocytes such as memory T cells, naïve B cells and immature dendritic cells. In this study, we investigated the expression of MIP-3 alpha and its specific receptor CCR6 in the inflamed joints of patients with RA. Increased amounts of MIP-3 alpha were found by ELISA in synovial fluids (SF) of patients with RA. MIP-3 alpha was apparently detected in all synovial tissue specimens of RA patients (n = 6), but it could not be detected in that of osteoarthritis (OA) patients (n = 4). Expression of MIP-3 alpha was detected especially in the sublining layer, and infiltrating mononuclear cells in RA synovial tissue. Gene expression of MIP-3 alpha was also found in six out of 11 RA-synovial fluid cells by RT-PCR. Cultured synovial fibroblasts derived from either RA or OA patients were capable of producing MIP-3 alpha in response to IL-1 beta and TNFalpha in vitro. Furthermore, expression of CCR6 was found in infiltrating mononuclear cells in the cellular clusters and around the vessels of RA synovial tissue. These findings indicate that increased production of MIP-3 alpha may contribute to the selective recruitment of CCR6-expressing cells in RA.
9712085 Analysis of type 1 and type 2 T cells in synovial fluid and peripheral blood of patients w 1998 Aug OBJECTIVE: It has been reported that CD4+ helper T cells play an important role in the pathogenesis of rheumatoid arthritis (RA). We evaluated the presence of intracellular cytokines interleukin 4 (IL-4) and interferon-gamma (IFN-gamma) produced by CD4+ and CD8+ T cells in the synovial fluid and peripheral blood of patients with RA at the single cell level. METHODS: We used 3 color flow cytometric analysis. Synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) were stimulated with phorbol myristate acetate (PMA) and calcium ionophore. The stimulated SFMC and PBMC were triple stained with conjugated mononuclear antibodies (Mab) against cytokines and surface antigens after fixation and permeabilization with a saponine buffer solution. The cells were analyzed for intracellular cytokines (IFN-gamma, IL-4) and surface antigens (CD3, CD4, CD8) using a flow cytometer. RESULTS: The CD4/CD8 ratio was significantly lower in SFMC than in PBMC. The positive rates of IFN-gamma producing cells among CD4+ T cells were significantly higher than those of IL-4 producing cells in both the SFMC and the PBMC of patients with active RA. In the SF of these patients, we also found CD8+ T cells that produce IL-4 alone, or both IL-4 and IFN-gamma. CONCLUSION: In the SF of patients with RA, CD4+ type 1 T cells, which may infiltrate into the synovium and cause pathogenic immune responses in the tissue, are predominant. We believe this cell type also induces migration and activation of CD8+ type 2 T cells into the active site of inflammation, which appears to downregulate the activity of CD4+ type 1 T cells, modulating the excess immune response.
11142075 A randomized controlled study of the Arthritis Self-Management Programme in the UK. 2000 Dec The objective of this study was to determine whether the Arthritis Self-Management Programme (ASMP) improves perceptions of control, health behaviours and health status, and changes use of health care resources. The design was a pragmatic randomized controlled study; participants were allocated to ASMP (Intervention Group) or a 4-month waiting-list Control Group. The Intervention Group completed a 12-month follow-up. In total, 544 people with arthritis were recruited from the community--311 in the Intervention Group and 233 in the Control Group. Main outcome measures included: arthritis self-efficacy, health behaviours (exercise, cognitive symptom management, diet and relaxation) and health status (pain, fatigue, anxiety, depression and positive affect). At 4 months follow-up, the ASMP had a significant effect on arthritis self-efficacy for other symptoms and pain subscales. Performance of a range of health behaviours (cognitive symptom management, communication with physicians, dietary habit, exercise and relaxation) was significantly greater among the Intervention Group. The Intervention Group were significantly less depressed and had greater positive mood. In addition, trends towards decreases on fatigue and anxiety were noted. Physical functioning, pain and GP visits remained stable at 4 months. A similar pattern of findings was found at 12 months follow-up for the Intervention Group. Furthermore, a significant improvement was found on pain and visits to GPs had decreased. Apart from a small improvement on physical functioning among the Intervention Group participants with osteoarthritis 12 months, all effects were independent of the type of arthritis. The findings suggest that the ASMP is effective in promoting improvements in perception of control, health behaviours and health status, when delivered in UK settings.
9733448 High dose versus low dose fludarabine in the treatment of patients with severe refractory 1998 Sep OBJECTIVE: Fludarabine, a nucleoside analog that targets both resting and proliferating lymphocytes, is a promising drug for the treatment of autoimmune diseases. We conducted a 2 dose, open label clinical trial to evaluate the toxicity/safety of the fludarabine treatment and its clinical and immunological effects. METHODS: Twenty-six patients with severe rheumatoid arthritis (RA) refractory to treatment with at least one slow acting antirheumatic drug were treated with intravenous fludarabine [20 mg/m2 body surface area (n=12) or 30 mg/m2 body surface area (n=14) per day for 3 consecutive days] given monthly for 6 months. Second line agents with the exception of glucocorticoids were discontinued at least 4 weeks before study entry. Measurements included toxicity and tolerability monitored at monthly intervals: efficacy, by both a 50% reduction in tender or swollen joint count and American College of Rheumatology (ACR) criteria for 20% response; and phenotypic analysis of peripheral blood mononuclear cells and T cell functional assays. RESULTS: Using intention-to-treat analysis, 2 of 12 (17%) patients in the low dose and 7 of 14 (50%) in the high dose groups had 50% or greater reduction in tender and/or swollen joint count after 6 months of therapy compared to baseline (p=0.09). Two of 12 (17%) in the low dose group and 5 of 14 (36%) in the high dose group met ACR criteria for 20% improvement (p=0.28). No immediate toxicity was observed. Several infections occurred, including 4 episodes of limited Herpes zoster, which responded to standard therapy. Significant lymphopenia involving T and B cells was observed in all patients. Both naive (CD4+CD45RA+) and memory CD4+ T cells (CD4+CD45RO+) were reduced (naive > memory). No significant regeneration of naive T cells was observed, which may suggest limited thymic regenerative capacity. Fludarabine decreased the proliferative response of peripheral blood lymphocytes to mitogens, as well as the production of T cell (interleukin 2 and interferon-gamma) and monocyte derived (tumor necrosis factor-alpha and IL-10) cytokines. CONCLUSION: Fludarabine treatment of patients with severe, refractory RA resulted in significant lymphopenia, suppression of lymphocyte function, and clinical improvement in the high dose group. There was no immediate toxicity; however, several infections occurred. Controlled trials are needed to substantiate the clinical improvement observed in this open label trial.
11718158 Celecoxib in osteoarthritis and rheumatoid arthritis: new preparation. As disappointing as 2001 Apr (1) The reference treatment for drug-based symptomatic relief of osteoarthritis and rheumatoid arthritis is paracetamol and low-dose ibuprofen. (2) The clinical file on celecoxib, a drug promoted as a selective COX-2 inhibitor, is bulky but fails to answer several practical questions, mainly because it lacks comparative trials against paracetamol and low-dose NSAIDs. (3) In osteoarthritis, three double-blind trials versus naproxen and placebo in a total of 3 258 patients show that the analgesic effect of celecoxib 200 mg/day is moderate and does not differ significantly from that of naproxen. Giving celecoxib in one or two daily doses makes no difference in terms of efficacy. (4) In rheumatoid arthritis, two double-blind trials against naproxen and placebo in a total of 2252 patients, and a double-blind trial versus sustained-release diclofenac, show that the symptomatic effect of celecoxib is moderate and no different from that of the comparator NSAIDs. (5) There is no evidence that the safety profile of celecoxib is very different from that of other NSAIDs. The advantage in terms of gastrointestinal adverse effects appears very slight. According to clinical trials and pharmacovigilance data, celecoxib is in no way exempt from the severe gastrointestinal adverse effects generally associated with NSAIDs. (6) In short, celecoxib changes nothing in the management of osteoarthritis and rheumatoid arthritis.
11093449 Patients with fibromyalgia have normal serum levels of hyaluronic acid. 2000 Nov OBJECTIVE: To investigate the levels of hyaluronic acid (HA) in Danish patients with fibromyalgia (FM). METHODS: Serum levels of HA were determined in 53 patients with established FM and 55 control samples using a radiometric assay. Values were correlated to clinical disease severity variables (duration of disease, tender point scales, visual analog scales). RESULTS: There were no differences in HA levels between patients and controls. HA levels of all patients except one were within the reference ranges. There was no association between HA levels and clinical findings. CONCLUSION: Patients with FM do not generally have increased serum levels of HA.
10076950 Measurement of clinical change caused by knee replacement. Conventional score or special c 1999 Clinical change may be measured with specific indexes of change or with the difference between single-state examinations. Change scores and transition indexes are the special indexes of change analysed in this study. At the 10-year follow-up of compartmental replacements, the conformity between subsequent Hospital for Special Surgery overall scores and the patient's opinion of change from before knee replacement was 0.54. This was judged to be unacceptable. It is recommended that a transitional index be included in the clinical evaluation systems used for knee replacement.
9252805 Arthrodesis of the first metatarsophalangeal joint to salvage failed silicone implant arth 1997 Jul Between 1987 and 1992, all patients presenting to the senior author with a symptomatic failed silicone implant arthroplasty refractory to conservative treatment were converted to a metatarsophalangeal joint arthrodesis. Internal fixation was achieved with either dual intrameduilary threaded Steinmann pins or an obliquely placed AO compression screw and a three- or four-hole one-third tubular dorsal neutralization plate. Bone grafting was used to maintain hallux length. Successful arthrodesis was achieved in all five feet in patients with rheumatoid arthritis. Subjectively, patients improved from an average of 0.69 before arthrodesis to 4.89 after arthrodesis. The average walking tolerance improved from 1.11 to 4.80, and the overall level of satisfaction improved from 0.0 to 4.79. The patient's ability to wear shoes improved from 0.87 to 3.1. Successful arthrodesis produces a foot that is more functional and durable than excisional arthroplasty. Subjectively, these patients stated that their level of pain, walking tolerance, and overall satisfaction improved significantly after the arthrodesis. Clinically, there was no evidence of transfer lesions, tenderness, or hallux subluxation. Hallux length was well maintained after surgery with bone grafting, but it was more difficult to obtain the alignment goals. The average postoperative metatarsophalangeal dorsiflexion angle was 15.6 degrees and the first metatarsophalangeal angle was 3.1 degrees. Despite this, patient satisfaction was high. Arthrodesis of the first metatarsophalangeal joint using a bone graft to salvage failed silicone implant arthroplasty produces acceptable subjective and radiographic results. Although technically demanding, it provides long-term stability to the hallux, restores weightbearing, and allows for maintenance of a propulsive gait. We recommend this procedure instead of an excisional arthroplasty to maintain high level of function and overall patient satisfaction.
9645397 Reactivity of cartilage and selected carbohydrates with hydroxyl radicals: an NMR study to 1998 Feb It was investigated to what extent isolated, monomeric and polymeric carbohydrates as well as cartilage specimens are affected by hydroxyl radicals generated by gamma-irradiation or Fenton reaction and what products can be detected by means of NMR spectroscopy. Resonances of all protons in glucose and other monosaccharides as well as carbon resonances in 13C-enriched glucose were continuously diminished upon gamma-irradiation. Formate and malondialdehyde were found as NMR detectable products in irradiated glucose solutions under physiologically relevant (aerated) conditions. In polysaccharide solutions (e.g. hyaluronic acid) gamma-irradiation and also treatment with the Fenton reagent caused first an enhancement of resonances according to mobile N-acetyl groups at 2.02 ppm. This indicates a breakdown of glycosidic bonds in polysaccharides. Using higher radiation doses or higher concentrations of the Fenton reagent formate was also detected. The same sequence of events was observed upon treatment of bovine nasal cartilage with the Fenton reagent. First, glycosidic linkages in cartilage polysaccharides were cleaved and subsequently formate was formed. In contrast, collagen of cartilage was affected only to a very low extent. Thus, HO-radicals caused the same action on cartilage as on isolated polymer solutions, inducing a fragmentation of polysaccharides and the formation of formate.
10090180 Shoulder involvement in rheumatic diseases. Sonographic findings. 1999 Mar OBJECTIVE: To distinguish using shoulder sonography the different changes present in rheumatoid arthritis (RA), polymyalgia rheumatica (PMR), and periarticular disorders (PD) of soft tissue of the shoulder. METHODS: Ninety shoulders of patients with RA, 32 with PMR, 122 with PD, and 108 controls were studied sonographically, using a 7.5 MHz linear probe. The following structures were evaluated: long head of biceps tendon, supraspinatus, infraspinatus and subscapularis tendons, subacromial and subscapularis bursae, rotator cuff (thickness), calcifications, and glenohumeral and acromioclavicular joints. Statistical analysis was by Student's t test and chi-squared test. RESULTS: Involvement of long head of biceps tendon (peritendinous fluid collection, changes of thickness, and/or echotexture) was significantly different between RA and PMR and between PD and PMR. Alterations in thickness and/or fibrillar pattern were evaluated in rotator cuff tendons: supraspinatus tendon was involved with significant differences between PD and both RA and PMR; the changes of subscapularis tendon were present, with significant differences between PD and both the other groups; the alterations of infraspinatus tendon were not statistically different between the 3 groups. Effusion within bursae was present, with significant differences only between RA and PD. The mean thickness of rotator cuff was significantly different between controls (6.2 mm) and both PD (5.3 mm) and RA (5.8 mm), and between PMR (6 mm) and PD. Evaluation of effusion within the glenohumeral joint (capsule-bone distance) showed significant differences between controls (2.4 mm) and both RA (4.2 mm) and PMR (4 mm), between RA and PD (2.6 mm), and between PMR and PD. Calcifications were present only in PD (21.3%) and RA (6.7%), with significant differences. Effusion within the acromioclavicular joint was present in RA (35.5%) and PD (20.5%), with significant differences. CONCLUSION: Shoulder sonography showed involvement of all structures in RA, the prevalence of effusion in PMR, and involvement mainly of tendons in PD.
11793168 Autologous bone grafting without screw fixation for tibial defects in total knee arthropla 2001 We evaluated 30 knees with autologous bone grafts, performed without screw fixation, for tibial defects in total knee arthroplasty (TKA). The tibial defects were classified into three types: contained, flat peripheral, and slant peripheral. The resected femoral condyle was fixed with a combination of bone cement and the tibial component, without using screws. The patients were followed for an average of 6 years and 10 months. In all knees except 1, the grafted bone united and formed good continuity with the tibial floor. Autologous bone grafting without screw fixation is a simple and effective method to deal with the tibial defects in primary TKA, especially for contained and flat peripheral defects.
11698466 NF-kappaB-inducing kinase is dispensable for activation of NF-kappaB in inflammatory setti 2001 Nov 15 The transcription factor NF-kappaB is of major importance in the biology of pro-inflammatory cytokines, such as TNF-alpha and IL-1alpha, and thereby is intimately involved in the process of inflammation. Understanding the mechanisms by which NF-kappaB is activated in response to inflammatory stimuli has become a major goal of inflammation research. The discovery of NF-kappaB-inducing kinase (NIK) as a TNFR-associated factor-interacting enzyme and a potential activator of the IkappaBalpha-kinase complex appeared to have identified an important element of the NF-kappaB activation pathway, a view that was supported by several subsequent studies. However, recent experiments in the alymphoplasia (aly/aly) mouse, which has missense point mutation (G885R) in NIK, has challenged that view. The reasons for the discrepancy between the different studies is unclear and could be due to multiple factors, such as cell type, species of cell, or primary vs transformed cell lines. One system that has not been investigated is primary human cells. Using an adenoviral vector encoding kinase-deficient NIK, we have investigated the role of NIK in LPS, IL-1, TNF-alpha, and lymphotoxin (LT) betaR signaling in primary human cells and TNF-alpha expression from rheumatoid tissue. These data show that, in the primary systems tested, NIK has a restricted role in LTbetaR signaling and is not required by the other stimuli tested. Also, there is no apparent role for NIK in the process of TNF-alpha production in human rheumatoid arthritis. These data also highlight the potential problems in extrapolating the function of signaling pathways between primary and transfected cell lines.