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ID PMID Title PublicationDate abstract
9022077 Inhibition of T cell apoptosis in the rheumatoid synovium. 1997 Feb 1 Synovial T cells in rheumatoid arthritis are highly differentiated and express a phenotype suggesting susceptibility to apoptosis (CD45RB dull, CD45RO bright, Bcl-2 low, Bax high, Fas high). However, no evidence of T cell apoptosis was found in synovial fluid from any of 28 patients studied. In contrast, synovial fluid from 10 patients with crystal arthritis showed substantial levels of T cell apoptosis. The failre of apoptosis was not an intrinsic property of rheumatoid synovial T cells, as they showed rapid spontaneous apoptosis on removal from the joint. Synovial T cells from rheumatoid arthritis and gout patients could be rescued from spontaneous apoptosis in vitro either by IL-2R gamma chain signaling cytokines (which upregulate Bcl-2 and Bcl-XL) or by interaction with synovial fibroblasts (which upregulates Bcl-xL but not Bcl-2). The phenotype of rheumatoid synovial T cells ex vivo (Bcl-2 low, Bcl-xL high) suggested a fibroblast-mediated mechanism in vivo. This was confirmed by in vitro culture of synovial T cells with fibroblasts which maintained the Bcl-xL high Bcl-2 low phenotype. Synovial T cells from gout patients were Bcl-2 low Bcl-xL low and showed clear evidence of apoptosis in vivo. Inhibition experiments suggested that an integrin-ligand interaction incorporating the Arg-Gly-Asp motif is involved in fibroblast-mediated synovial T cell survival. We propose that environmental blockade of cell death resulting from interaction with stromal cells is a major factor in the persistent T cell infiltration of chronically inflamed rheumatoid synovium.
10531076 Expression of adhesion molecules on synovial fluid and peripheral blood monocytes in patie 1999 Nov OBJECTIVE: To determine the presence of adhesion molecules on monocytes/macrophages (Mphi) from peripheral blood (PB) and synovial fluid (SF) in patients with osteoarthritis (OA) and inflammatory joint diseases (rheumatoid (RA) and reactive arthritis (ReA)) in order to improve our understanding of the possible mechanisms underlying the inflammatory process. METHODS: Whole blood and SF cells were stained with monoclonal antibodies against CD11a (LFA-1), CD15 s (sialyl-Lewis X), CD44, CD54, VLA-4, and HLA-DR counterstained with anti-CD14 antibodies as a Mphi marker for dual fluorescence analysis by flowcytometry. RESULTS: On PB-Mphi, CD15s was markedly increased in both RA as well as ReA compared with OA. Furthermore, in the PB LFA-1, CD44, and HLA-DR showed a higher surface density on Mphi in ReA than in OA. Comparison between SF and PB showed significantly higher CD44 and CD54 expression on SF-Mphi. These molecules play an important part in lymphocyte-Mphi interaction. CONCLUSION: In PB from patients with inflammatory joint diseases, Mphi are activated, allowing recruitment into the synovial compartment. These disorders, in contrast with OA seem to be "systemic" in nature. Within the SF, different adhesion molecules are expressed on CD14(+) Mphi as compared with PB.
11229456 Overexpression of transcription factor Ets-1 in rheumatoid arthritis synovial membrane: re 2001 Feb OBJECTIVE: To investigate the expression of the transcription factor Ets-1 in synovial tissue and cultured synovial fibroblasts from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to study the regulation of Ets-1 expression and activation in synovial fibroblasts by proinflammatory cytokines. METHODS: In situ expression of Ets-1 in synovial tissue from RA and OA patients was examined by double immunohistochemistry. The effects of interleukin-1 (IL-1) or tumor necrosis factor alpha (TNFalpha) on Ets-1 expression and activation (DNA binding) in cultured synovial fibroblasts were analyzed by Western blotting and DNA gel shift assay, respectively. In addition, the intracellular location of Ets-1 in synovial fibroblasts was determined by immunofluorescence. RESULTS: Pronounced expression of Ets-1 was detected in synovial tissues from all RA patients evaluated, particularly in the synovial lining layer and the sublining areas. Ets-1 was expressed by both fibroblasts and macrophages as well as by endothelial cells, while only a few T cells stained positive for Ets-1. In synovial specimens from OA patients, Ets-1 expression was much less frequently observed and was largely restricted to vascular cells. Ets-1 was expressed to a similar degree in cultured synovial fibroblasts from RA and OA patients, as demonstrated by reverse transcriptase-polymerase chain reaction and Western blotting. Both IL-1 and TNFalpha induced pronounced up-regulation of Ets-1 in synovial fibroblasts. Moreover, binding of Ets-1 to its specific DNA binding site was induced by both cytokines, although with different time courses. Immunofluorescence staining revealed a dominant nuclear localization of Ets-1 in IL-1- or TNFalpha-stimulated synovial fibroblasts. CONCLUSION: The overexpression of Ets-1 observed in RA synovial tissue appears to be caused by TNFalpha and IL-1, suggesting that Ets-1 may be an important factor in the cytokine-mediated inflammatory and destructive cascade characteristic of RA.
11048656 Autoantibodies against chaperonin CCT in human sera with rheumatic autoimmune diseases: co 2000 Oct Chaperonin CCT containing t-complex polypeptide 1 is a cytosolic molecular chaperone that assists in the folding of actin, tubulin, and other proteins and is a member of the 60-kDa heat shock protein (Hsp60) family. We examined antibody titers against human CCT and other Hsp60 family members in the sera of patients with rheumatic autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematodes, Sjögren syndrome, and mixed connective tissue disease. Autoantibody titers against not only human mitochondrial Hsp60 but also CCT were significantly higher in the sera of patients with rheumatic autoimmune diseases than in healthy control sera. Although immunoglobulin G (IgG) titers against Escherichia coli GroEL were high in all the groups of sera tested, no significant differences in anti-GroEL responses were detected between patients and healthy controls. IgG titers against mycobacterial Hsp65 showed a similar pattern to titers of autoantibodies recognizing GroEL. Immunoabsorption experiments demonstrated that most of the autoantibodies recognizing CCT were cross-reactive with mitochondrial Hsp60, E coli GroEL, and mycobacterial Hsp65. Although most of the anti-Hsp60 IgG recognized CCT, anti-GroEL (or antimycobacterial Hsp65) IgG contained antibodies specific for GroEL (or mycobacterial Hsp65) in addition to antibodies cross-reactive with CCT and Hsp60. Results from immunoblot analyses, together with weak (15% to 20%) amino acid sequence identities between CCT and the other Hsp60 family members, suggested that CCT-reactive autoantibodies recognize conformational epitopes that are conserved among CCT and other Hsp60 family members.
10196612 Functional improvement after knee arthroplasty without resurfacing of patella. 1998 There has been no universal agreement so far regarding the necessity of patellar resurfacing in total knee arthroplasty. As resurfacing has been reported to be associated with high incidence of complications, this practice has been avoided in our Department. A report is given on the analysis of the functional outcome of 60 knee arthroplasties without patellar resurfacing in 53 patients (7 bilateral) followed up for twelve to thirty months, with special regard to the functions closely related to patelloformal articulation. The underlying diagnosis was osteoarthritis in 78.3%, rheumatoid arthritis in 13.3%, and posttraumatic arthritis in 8.3% of the patients. Graded according to the modified knee-rating system of the Hospital for Special Surgery, excellent or good results were obtained in the case of 55 knees (91.6%) and the mean score improved from 53.6 points preoperatively to 82.6 points following arthroplasty. Subjective and objective functional assessment of stair climbing and transfer activities have shown no functional deficit attributed to the patellofemoral joint of the replaced knee.
11467897 The effect of dynamic mechanical compression on nitric oxide production in the meniscus. 2001 Jul OBJECTIVE: The menisci play an important role in the biomechanics of the knee, and loss of meniscal function has been associated with progressive degenerative changes of the joint in rheumatoid arthritis as well as in osteoarthritis. However, little is known about the underlying mechanisms that link meniscal injury or degeneration to arthritis. Meniscal fibrochondrocytes respond to environmental mediators such as growth factors and cytokines, but the influence of mechanical stress on their metabolic activity is not well understood. Nitric oxide (NO) is believed to play a role in mechanical signal transduction, and there is also significant evidence of its role in cartilage and meniscus degeneration. The goal of this study was to determine if meniscal fibrochondrocytes respond to mechanical stress by increasing NO production in vitro. DESIGN: Explants of lateral and medial porcine menisci were dynamically compressed in a precisely controlled manner, and NO production, nitric oxide synthase antigen expression and cell viability were measured. The relative responses of the meniscal surface and deep layers to dynamic compression were also investigated separately. RESULTS: Meniscal NO production was significantly (P< 0.01) increased by dynamic compression in both the medial and lateral menisci. Dynamically compressed menisci contained inducible nitric oxide synthase antigen, while uncompressed menisci did not. Significant (P< 0.05) zonal differences were observed in basal and compression-induced NO production. DISCUSSION: Our findings provide direct evidence that dynamic mechanical stress influences the biological activity of meniscal cells. These results suggest that NO production in vivo may be in part regulated by mechanical stress acting upon the menisci. Since NO affects matrix metabolism in various intraarticular tissues, alterations in the distribution and magnitude of stress in the menisci may have important metabolic as well as biomechanical consequences on joint physiology and function.
11155807 The hypothalamic-pituitary-adrenocortical and gonadal axis function in rheumatoid arthriti 2000 The altered cortisol and adrenal androgen (i.e., dehydroepiandrosterone sulfate = DHEAS) secretion, observed during testing in rheumatoid arthritis (RA) patients not treated with corticosteroids, should be clearly regarded as a "relative adrenal insufficiency" in the setting of a sustained inflammatory process, as shown by high serum IL-6 levels. Androgens seem implicated in the pathophysiology of autoimmune disorders, including RA, as natural immunosuppressors. Low plasma and synovial fluid testosterone concentrations are observed in male RA patients; low plasma DHEAS levels are mainly observed in female RA patients. The menopausal peak of RA suggests that estrogens and/or progesterone deficiency also play a role in the disease, and many data indicate that estrogens suppress cellular immunity, but stimulate humoral immunity (i.e., deficiency promotes cellular Th1-type immunity). Gene polymorphisms for enzymes involved in the steroidogenesis seem to further complicate the role of sex hormones in the susceptibility to autoimmunity. Acquired changes of sex steroid metabolism seem to also play a role in the peripheral sex hormone levels. In conclusion, a complex interaction between the hypothalamus-pituitary-adrenocortical and gonadal axis functions is evident in RA.
11585341 Acid attack and cathepsin K in bone resorption around total hip replacement prosthesis. 2001 Oct Normal bone remodeling and pathological bone destruction have been considered to be osteoclast-driven. Osteoclasts are able to attach to bare bone surface and produce an acidic subcellular space. This leads to acid dissolution of hydroxyapatite, allowing cathepsin K to degrade the organic type I collagen-rich osteoid matrix under the acidic condition prevailing in Howship lacunae. Using a sting pH electrode, the interface membrane around a loosened total hip replacement prosthesis was found to be acidic. Confocal laser scanning disclosed irregular demineralization of the bone surface in contact with the acidic interface. Cathepsin K, an acidic collagenolytic enzyme, was found in interface tissue macrophages/giant cells and pseudosynovial fluid. Tissue extracts contained high levels of cathepsin K messenger RNA (mRNA) and protein. These observations suggest the presence of an acid- and cathepsin K-driven pathological mechanism of bone resorption, mediated not by osteoclasts in subosteoclastic space, but rather by the uncontrolled activity of macrophages in extracellular space.
10399223 [Soluble adhesion molecules (P-selectin, ICAM-1 and ICAM-3) in rheumatoid arthritis]. 1999 AIM: Investigation of serum levels and clinical role of soluble intercellular molecules of adhesion (pICAM-1, PICAM-3 and pP-selectin) in rheumatoid arthritis (RA). MATERIALS AND METHODS: Enzyme immunoassay with Bender MedSystem kits (Austria) was employed to measure serum concentration of soluble intercellular molecules of adhesion in 36 RA patients. RESULTS: Elevated levels of serum pICAM-1, pICAM-3 and pP-selectin were registered in 74.2, 28.6 and 25.7% of RA patients, respectively. Content of pP-selectin more strongly correlated with activity and severity indices than that of pICAM-3 (p < 0.001). Content of pICAM-1 and clinical picture of RA were unrelated. CONCLUSION: Levels of pP-selectine can characterize RA activity.
10092102 Frequent enrichment for CD8 T cells reactive against common herpes viruses in chronic infl 1999 Mar We recently evidenced a dramatic enrichment for T cells reactive against Epstein-Barr virus (EBV) within inflamed joints of two rheumatoid arthritis patients. To assess the generality of this phenomenon and its relevance to autoimmunity, we studied the responses of CD8 T cells from patients with either acute or chronic inflammatory diseases (rheumatoid arthritis: n = 18, ankylosing spondylitis: n = 5, psoriatic arthritis: n = 4, Reiter's syndrome: n = 3, arthrosis: n = 2, uveitis: n = 2, multiple sclerosis: n = 2, encephalitis: n = 1) against viral proteins derived from EBV and another common herpes virus, human cytomegalovirus (CMV). T cell responses against EBV and/or CMV epitopes were frequently observed within CD8 T cells derived from chronic inflammatory lesions, irrespective of their location (knee, eye, brain) and autoimmune features. In most cases, CD8 T cells derived from affected organs yielded stronger anti-viral T cell responses than CD8 T cells derived from patients' PBL, even in chronic inflammatory diseases devoid of autoimmune features or induced by defined bacterial agents. Taken together, these results suggest that the presence of virus-specific T cells within inflamed lesions of patients suffering from autoimmune diseases is a general phenomenon associated with chronic inflammation rather than the initiating cause of the autoimmune process. Since this phenomenon was sometimes associated with long-term T repertoire biases within inflamed lesions, the physiopathological significance of T cell clonal expansions found in a recurrent fashion within chronically inflamed autoimmune lesions should be interpreted with caution.
10692038 Relationship between disease severity and responses by blood mononuclear cells from patien 2000 Feb The hypothesis that T-cell responses to the 60 000 MW family of heat-shock proteins (hsp) may be related to the severity of rheumatoid arthritis (RA) was examined. Peripheral blood mononuclear cells (PBMC) from most normal individuals and both early and established RA patients proliferated in vitro in response to human hsp 60 and mycobacterial hsp 65 as well as tetanus toxoid (TT) and mycobacterial purified protein derivative (PPD). PBMC from some patients with established RA gave responses to hsp 60 that were above the normal range and/or peaked earlier than PBMC from normal individuals. The responses of PBMC from established RA to hsp 65, but not PPD or TT, were also higher than those from normal individuals, but the peak responses to all three antigens appeared delayed. Thus a selective increase in responsiveness to hsp 60 develops with disease duration in many RA patients. Six assessments of disease activity and severity were made but apart from rheumatoid factor titre, they were unrelated to the proliferative response. Similarly, disease activity and severity did not differ between those RA patients whose hsp 60 stimulated cells produced interferon-gamma and those who did not, although patients whose hsp 60-stimulated T cells produced interleukin-4 (IL-4) and/or IL-10, appeared to have less disease activity and severity than those who did not. Significant negative correlations were found between IL-10 production by hsp 60-stimulated cells and disease assessments. It is considered that RA is less severe in those patients whose hsp 60-stimulated cells produce T-helper 2 type cytokines.
11263769 Levels of interleukin-18 and its binding inhibitors in the blood circulation of patients w 2001 Mar OBJECTIVE: Interleukin-18 (IL-18) is a proinflammatory cytokine that is involved in immunologically mediated tissue damage, but its bioactivity is regulated in vivo by its soluble decoy receptor, IL-18 binding protein (IL-18BP). This study was undertaken to determine levels of IL-18 and IL-18 binding inhibition in the blood of patients with adult-onset Still's disease (ASD). METHODS: Serum concentrations of IL-18 in ASD patients were compared by enzyme-linked immunosorbent assay (ELISA) with those in patients with other systemic rheumatic diseases and healthy controls. The biologically active mature protein of IL-18 was detected by Western blot analysis with anti-IL-18 antibody and its induction of interferon-gamma (IFNgamma) secretion from IL-18-responding human myelomonocytic KG-1 cells. The inhibitory activity on IL-18 binding to its receptor was determined by 125I-IL-18 binding inhibition assay using the Chinese hamster ovary cell line transfected with a murine IL-18 receptor (CHO-K1/mIL-18R). RESULTS: Concentrations of serum IL-18 were extremely elevated in patients with active ASD compared with those in patients with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, polymyositis/dermatomyositis, Sjogren's syndrome, or healthy individuals. Levels of IL-18 were found to correlate with serum ferritin values and disease severity in ASD. Western blot analysis revealed that serum samples from patients with active ASD contained an 18-kd polypeptide of IL-18, corresponding in size to the mature form. Accordingly, the samples were able to induce IFNgamma secretion from KG-1 cells, which was largely abolished by neutralizing anti-IL-18 antibody. However, the level of IL-18 bioactivity was more than 10-fold weaker than the concentration of IL-18 protein measured by ELISA. Serum samples from patients with active ASD showed an inhibitory effect on the binding of 125I-IL-18 to CHO-K1/mIL-18R cells, and this activity was associated with elevation of IL-18. CONCLUSION: These data indicate that systemic overproduction of IL-18 may be closely related to the pathogenesis of ASD, despite the restriction on its inflammatory activity by IL-18 binding inhibitors such as IL-18BP. The disease activity appears to be determined on the basis of the relative levels of IL-18 and its specific inhibitors.
9038102 IgG rheumatoid factors isolated by the surface-displaying phage library technique. 1997 Our analysis of IgG rheumatoid factors (RFs) from three patients with rheumatoid arthritis (RA) revealed that most contained significant numbers of skewed mutations per V region, suggesting that these RFs arose from antigen-driven responses. To further study IgG RFs in RA, we used pComb3 vector to construct an IgG1,lambda combinatorial antibody library from a synovial fluid sample. After panning against human IgG, Fab fragments from 71/96 phage clones bound to Fc-coated wells. Sequence analysis of 20 randomly chosen Fc-binders showed that 17 (85%) clones had identical heavy (H) and light (L) chain V regions, represented by Humha311 and Humla211, respectively. Of the remaining three clones, two had the same Humla211 L chain, but each with a different H chain V region. All the putative germline V genes for these RFs also encode RF in RA patients. However, none of these RF V regions are similar to those of the two IgG RFs derived by the hybridoma technique from the same synovial fluid. The Humha311 H chain has two frameshifts: a one-base insertion upstream of the JH region and a four-base deletion near the end of the CH1 region, resulting in a mainly unconventional amino acid sequence in the CH1 region. In the future, it will be important to study the presence of IgG molecules with such unconventional CH1 amino acid sequences, and the effects of these amino acid sequences on the structures and immunological properties of the IgG molecules.
9726316 Universal Total Wrist Implant: experience with a carpal component fixed with three screws. 1998 Aug The Universal Wrist Implant was used to treat 31 patients (37 wrists), who had symptoms indicating pancarpal arthritis of the wrist, diagnosed as total wrist arthroplasty. Their mean age was 58.1 years. Follow-up ranged from 48 to 120 months with a mean of 79.4 months (6.7 years). The carpal component of the Universal Total Wrist is fixed to the carpus by titanium screws. Unlike other total wrist prostheses, the primary fixation of the carpal component is in the capitate and not in the third metacarpal. Intercarpal fusion provides a solid bony support for the carpal plate and results in improved longevity. Articular surface of the radial component is inclined 20 degrees, similar to the articular surface of the radius. Components can be inserted with or without cement. In three patients, the prosthesis had to be removed due to infection and persistent dislocation. Of the remaining 34 wrists, 30 (88%) achieved excellent pain relief. Complications occurred in 12 cases (32%). Of these 12 complications 9 (75%) resolved with appropriate treatment. The most common complication with this nonconstrained prosthesis was dislocation. The Universal Total Wrist Implant provides a predictable option to preserve motion and relieve pain when managing wrist joint arthritis.
10525690 [Short- and mid-term results with the STAR total ankle prosthesis]. 1999 Sep We evaluated the short- to mid-term results of an unconstrained total ankle prosthesis (S. T. A. R.) with uncemented fixation. Fifty consecutive ankle replacements were performed in 48 patients between 1996 and 1999. The initial diagnosis was posttraumatic osteoarthrosis in 31 cases (62 %), primary osteoarthrosis in 8 cases (16 %), and systemic joint affection in 11 cases (22 %), e. g. rheumatoid arthritis (6 cases), hemochromatosis (2 cases), psoriasis arthritis (1 case), lupus erythematodes (1 case), and sclerodermia (1 case). There were two perioperative complications: one superficial wound dehiscence that healed uneventfully, and one injury to the dorsal foot artery that necessitated primary reconstruction. Seven revisions, all in cases of posttraumatic arthrosis, were necessary: local revision of the fibula for painful lateral impingement (3 cases), posteromedial soft tissue revision for painful restriction of dorsiflexion (2 cases), percutaneous lengthening of the Achilles tendon (1 case), and osteotomy and callus distraction for angular correction after stress fracture of the distal tibia (1 case). At the last follow-up control, 21 patients (62 %) were very satisfied, 10 patients (29 %) were satisfied, and 3 patients (9 %) were satisfied with reservations. The obtained range of motion was 30 degrees (range, 15 to 55 degrees ), with a maximal plantarflexion of 25 degrees (range, 15 to 45 degrees ) and dorsiflexion of 5 degrees (-3 to 20 degrees ). When the AOFAS-Hindfoot-Score was applied, the 34 patients scored 84.1 points (range, 44 to 100 points). After settling of the implants within 6 weeks, no migration was noted in any case, and all implants were considered to be stable. The favorable results were considered to be a result of the mechanical properties of the S. T. A. R. total ankle prosthesis that allows for unconstrained motion of the polyethylene inlay on the tibial component, e. g. anteroposterior translation, mediolateral translation and axial rotation. The success of implantation may depend on exact technique, correct hindfoot alignment, sufficient capsuloligamentous stability of the ankle, and a solid bone stock. Although our first results are very encouraging, a longer follow-up is mandatory to answer the question whether ankle replacement is a viable alternative to ankle arthrodesis.
9292788 Dominant T cell receptor rearrangements in interleukin 2 expanded lymphocytes from rheumat 1997 Sep OBJECTIVE: To study at a molecular level the clonality of interleukin 2 (IL-2) expanded T cell lines derived from rheumatoid nodules. Such cell lines were reported in earlier studies with flow cytometry and antiidiotypic monoclonal antibodies (MAb) to be obligoclonal. METHODS: T cell lines were derived from rheumatoid nodules in 2 patients with rheumatoid arthritis (RA) and expanded in medium containing IL-2. Clonality was assessed by flow cytometry and T cell receptor (TCR) idiotype specific Mab and by polymerase chain reaction with primers for V alpha and V beta gene families. Sequence analysis was performed in selected cell lines. RESULTS: In one patient, one cell line was identified with marked overexpression of V alpha 2 cells. Eleven V alpha 2 CDR3 sequences were derived from this cell line: 8 of these clones had an identical CDR3 sequence and one other clone showed a related sequence. Five cell lines derived from a second patient displayed a marked clonal bias to V beta 8 cells. One cell line with strong V beta 8 expression was chosen for further sequence analysis. Twelve V beta 8 sequences were obtained; 11 showed identical CDR3 sequences. CONCLUSION: Molecular analysis of TCR rearrangements in IL-2 expanded T cell lines from rheumatoid nodules strongly suggests that in situ T cell activation is related to classical antigen induced immune activation.
11592364 Presence of a population of CD20+, CD38- B lymphocytes with defective proliferative respon 2001 Sep OBJECTIVE: To provide a comprehensive understanding of the humoral immune response that takes place at the site of inflammation in rheumatoid arthritis (RA), we studied the functional properties of synovial B cells. In particular, the response to various modes of mitogen stimulation was investigated. METHODS: Purified synovial fluid (SF) B cells were cultured in the presence of CD40 ligand (CD40L)-expressing fibroblasts and cytokines, activated T cells, or phorbol myristate acetate (PMA)/ionomycin. Proliferation was determined by 3H-thymidine incorporation. Release of intracellular calcium was studied by flow cytometry. RESULTS: The inflamed joints of RA patients contained a population of CD20+,CD38- B cells with dramatically impaired mitogen responsiveness. Although the Ig-producing capacity was intact, these cells failed to proliferate in response to (a) CD40 in the presence of interleukin-2 (IL-2) and IL-10, (b) activated T cells, or (c) stimulation via the B cell receptor. Moreover, SF CD20+,CD38- B cells revealed a defective B cell receptor-induced Ca2+ influx, reminiscent of anergic B cells. Release of intracellular Ca2+ by ionomycin in the presence of the protein kinase C activator PMA did not restore the proliferative capacity. These findings indicate blockades in the proximal and distal intermediates involved in mitogen signaling. CONCLUSION: SF CD20+,CD38- B cells have functionally impaired proliferative responsiveness. The capacity of these cells to respond to activation by the production of Ig supports the notion that these cells might serve as Ig-producing effector cells and, as such, play a role in the pathophysiology of RA.
11171681 Inappropriate medical management of spinal epidural abscess. 2001 Mar A 67 year old man with longstanding rheumatoid disease was referred to the regional spinal surgery unit with acute onset of paraparesis due to an extensive spinal epidural abscess of the lumbar spine. Ten months previously, he had started antibiotic treatment at another hospital for an epidural abscess arising at the level of the L2-3 disc space. Despite completing seven months of medical treatment with appropriate antibiotics, he had a recrudescence of acute back pain shortly after restarting methotrexate treatment. Urgent anterior spinal decompression with excision of the necrotic vertebral bodies of L1-3 was performed. The indications for the surgical management of spinal epidural abscess are reviewed.
11119246 Longevity of immune complexes and abnormal germinal centre formation in NZB mice. 2000 Nov Rheumatoid factor (RF)-like (antibody-antibody) immune complexes induce a selective and intensive immunoglobulin (Ig)G1-RF response after a single injection in mice. However, the longevity of the response differs between mouse strains: serum IgG1-RF antibody titres decline 40 days after injection in C57Bl/6 mice whereas levels are maintained for more than 100 days in NZB mice. In order to elucidate whether this difference was owing to a lower ability of NZB mice to clear the injected immune complexes, sections of kidney, spleen, liver and mesenteric lymph nodes were harvested at different time points after injection with RF-like immune complexes. Immunohistochemical staining revealed that NZB mice have a delayed clearance of the injected immune complexes, because the immune complexes are retained for more than 40 days in their spleens and 100 days in their kidneys, compared to only 14 days in C57Bl/6 mice. Germinal centres were also present for a longer period in the spleens of the NZB mice, accompanying the presence of the immune complexes, and were abnormally large compared to C57Bl/6 mice. The clearance of immune complexes from the spleen coincided with the decline in serum levels of IgG1-RF, indicating that prolonged retention of immune complexes is responsible for the sustained IgG1-RF response.
10724046 The effects of immunosuppressive and anti-inflammatory medications on fertility, pregnancy 2000 Mar 13 Many rheumatic diseases affect women of childbearing age, and the medications used to treat these diseases may affect conception, pregnancy, fetal development, and lactation. Physicians who care for these women need to be aware of the potential adverse effects of these medications, and which medications can be used safely prior to conception and during pregnancy and lactation. Although reviews of individual classes of medications are available, there is no practical and comprehensive review that summarizes all of this information, and includes anticoagulant drugs and 2 recently approved drugs for rheumatoid arthritis. Women who take cytotoxic drugs should be informed of the risks of impaired fertility and congenital malformations, and must use effective methods of contraception. During pregnancy, nonsteroidal anti-inflammatory agents may be used until the last 6 weeks, and low to moderate doses of corticosteroids are safe throughout pregnancy. Among the disease-modifying agents, sulfasalazine and hydroxychloroquine treatment may be maintained. Cytotoxic drugs may be used after the first trimester to treat life-threatening disease. During lactation, prednisone, sulfasalazine, and hydroxychloroquine may be used cautiously. Women using heparin for treatment of antiphospholipid antibody syndrome should take measures to prevent bone loss. Men taking methotrexate, sulfasalazine, cyclosporine, azathioprine, or leflunomide should be apprised of the possibilities of infertility and teratogenicity.