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ID PMID Title PublicationDate abstract
7900728 Pneumoconiosis and associated medical conditions. 1995 Jan Hospital discharge data from Michigan for the years 1990 and 1991 were used to examine potential associations between pneumoconiosis and pulmonary hypertension, lung cancer, obstructive lung disease, and connective tissue disease among both men and women. Lung cancer, pulmonary hypertension, and obstructive lung disease were associated with coal workers' pneumoconiosis. Pulmonary hypertension and obstructive lung disease were associated with asbestosis and silicosis. Rheumatoid arthritis was associated with silicosis. The potential is suggested that misdiagnosis is the cause of the association between lung cancer and coal workers' pneumoconiosis.
1592211 Antibodies against crystals. 1992 May We suggest that crystals, when introduced into an organism, may behave as conventional antigens, mediating the production of specific antibodies. These antibodies would bear an imprint of the crystal surface and may consequently behave as a nucleating matrix in a new crystallization event. Thus, they would behave as catalytic antibodies. We show that IgG antibodies isolated from patients suffering from gout, a joint disease caused by crystals of monosodium urate monohydrate (MSUM), accelerate the appearance of new crystals of MSUM from a supersaturated solution of the salt in vitro. The same effect is not observed for IgG antibodies isolated from the joint fluids of patients with other joint diseases, such as pseudogout, rheumatoid arthritis, or osteoarthritis. Furthermore, IgG antibodies obtained from rabbits injected subcutaneously with crystals of MSUM, were also nucleating towards MSUM crystals.
8591651 Innovative treatment approaches for rheumatoid arthritis. New cyclo-oxygenase and cytokine 1995 Nov A need remains for the development of more effective therapies for the treatment of rheumatoid arthritis (both NSAIDs and DMARDs). The NSAIDs remain the cornerstone of symptomatic therapy, but concern remains about their safety, potential for the delay in commencing definitive therapy and theoretical pro-inflammatory effects. Each of the NSAIDs reviewed here do provide an advantage over therapies previously available and should prove to be useful additions to the rheumatologists' therapeutic armament.
7686370 Reduced synovial membrane macrophage numbers, ELAM-1 expression, and lining layer hyperpla 1993 Jul OBJECTIVE: To define the immunohistologic features of the synovial membrane (SM) of patients with psoriatic arthritis (PA) and to compare them with those of an age- and disease-duration-matched population of patients with rheumatoid arthritis (RA). METHODS: Synovial membrane needle biopsy was performed on 15 PA patients with knee involvement (8 had asymmetric oligoarthritis and 7 had symmetric polyarthritis) and on 15 RA controls. Specimens were stained with monoclonal antibodies against T cells (CD3, CD8, CD4, CD45RO), B cells (CD20), macrophages (Mac387, CD14), and cells bearing class II antigens (DAKO-DR). Vascular endothelium was examined using a polyclonal antibody to Factor VIII-related antigen, and adhesion molecule expression was examined using antibodies 1.3B6, 6.5B5, and 1.4C3, which identify endothelial leukocyte adhesion molecule 1 (ELAM-1), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1), respectively. RESULTS: There was significantly less lining layer hyperplasia, fewer macrophages, and a greater number of blood vessels in PA SM than in RA SM: ELAM-1 expression was less intense in PA than in RA SM, while there was no difference in expression of ICAM-1 and VCAM-1. Numbers of B cells, T cells, and T cell subsets (predominantly CD4, CD45RO T cells) were similar in both groups of patients. CONCLUSION: Our findings demonstrate important differences in the immunohistologic features of PA and RA SM: The PA SM is more vascular, ELAM-1 expression is less intense, and fewer macrophages invade the stroma and migrate to the lining layer than in RA SM: However, the lymphocytic infiltrate in the SM of both groups is similar.
1334358 Involvement of the kinin-forming system in the physiopathology of rheumatoid inflammation. 1992 Kinins are potent mediators of rheumatoid inflammation. The components of the kinin-forming system are hyperactive in RA. Excessive release of kinins in the synovial fluid can produce oedema, pain and loss of functions due to activation of B1 and B2 receptors. These receptors could be stimulated via injury, trauma, coagulation pathways (Hageman factor and thrombin) and immune complexes. The activated B1 and B2 receptors might cause release of other powerful non-cytokines and cytokines mediators of inflammation, for example, PGE2, PGI2, LTs, histamine, PAF, IL-1 and TNF derived mainly from polymorphonuclear leukocytes, macrophages, endothelial cells and synovial tissue. These mediators are capable of inducing bone and cartilage damage, hypertrophic synovitis, vessels proliferation, inflammatory cells migration, and possibly angiogenesis in pannus formation. These pathological changes, however, are not yet defined in human model of chronic inflammation (RA). Hence, the role of kinin and its interacting inflammatory mediators would soon start to clarify the detailed questions they revealed in clinical and experimental models of chronic inflammatory joint diseases. Several B1 and B2 receptor antagonists are being synthesized in an attempt to study the molecular functions of kinins in inflammatory processes (RA, periodontitis and osteomyelitis), and they represent and important area for continued research in rheumatology. Future development of specific, potent and stable B1 and B2 receptor antagonists or combined B1 and B2 antagonists with y-IFN might serve as pharmacological basis of more effective rationally-based therapies for RA. This may lead to significant advances in our knowledge of the mechanisms and therapeutics of rheumatic diseases.
8582468 Serum kinetics, bioavailability and bone scanning of 99mTc-labelled sodium olpadronate in 1995 The activity of olpadronate labelled with technetium-99m(99mTc) was monitored in plasma and urine samples after single oral (925 MBq 99mTc/10 mg, coadministered with 50 mg cold drug) and intravenous (925 MBq 99mTc/5 mg) administrations to two groups of patients with different rates of bone turnover. The first group comprised high bone turnover (HBTO) patients suffering from Paget's bone disease; the second group comprised patients with normal to low bone turnover (NBTO) having the diagnosis of rheumatoid arthritis and secondary osteoporosis. Kinetic variables were correlated with anthropomorphometric variables, biological markers of bone metabolism and plasma proteins. Data were also obtained after repeatedly dosing the HBTO patients. Additionally, Paget's bone and healthy bone (PB/HB) uptake before and after low-dose oral treatment were assessed by means of scintigraphy. Results showed that most of the kinetic variables did not differ between the two groups of patients, except for a greater Vss and smaller blood area under the curve AUC in the patients with HBTO. After a repeated-dose administration period, the blood AUC activity and Whole Body Retention (WBR) of the HBTO patients tended to be similar to those of the NBTO patients. In both groups, after oral dosing, the Cmax was 20 times lower than the C0.5 after i.v. injection, and the oral bioavailability ranged from 3% to 4%. Finally, the plasma t1/2 beta ranged from 9 to 14 h. Correlation coefficients were obtained from multiple regression analysis; kinetic variables showed very low correlations with anthropomorphometric measurements. In contrast the Vss and WBR were significantly correlated with serum alkaline phosphatase levels and the Vss also with urine hydroxyproline levels. Plasma protein concentration was also correlated with excretion parameters such as CLP and plasma t1/2 beta after an oral dose. Scintigraphic studies in the HBTO group allowed bone selectivity to be seen through skeletal drug uptake. The 15 Pagetic lesions analysed in the HBTO group showed a decrease in PB/HB ratio from 3.8 in the basal study to 2.7 after olpadronate administration for 30 days at the rate of 50 mg/day. In conclusion, the kinetic profile of 99mTc-labelled olpadronate, mainly AUC and WBR, showed a dependence upon bone metabolism and seemed unrelated to body size variables. HBTO patients showed a lower blood AUC but a higher Vss. Both variables may have been reflecting the fact that the drug binds selectively with calcified tissues and, in turn, with the target compartment. Scintigraphy confirmed the labelled-compound bone selectivity as a desirable feature for a bone-scanning agent.
9036720 [[Gold antirheumatic drug: desired and adverse effects of Au(I) and Au(III) [corrected] on 1996 Sep Three new findings are reviewed that help to understand the mechanisms of action of anti-rheumatic gold drugs, such as disodium aurothiomalate (Na2Au(I)TM): i) We found that Na2Au(I)TM selectively inhibits T-cell receptor-mediated antigen recognition by murine CD4+ T-cell hybridomas specific for antigenic peptides containing at least two cysteine residues. Presumably, Au(I) acts as a chelating agent forming linear complexes (Cys-Au(I)-Cys) which prevents correct antigen-processing and/or peptide recognition by the T-cell receptor, ii) We were able to show that Au(I) is oxidized to Au(III) in mononuclear phagocytes, such as macrophages. Because Au(III) rapidly oxidizes protein and itself is re-reduced to Au(I), this may introduce an Au(I)/Au(III) redox system into phagocytes which scavenges reactive oxygen species, such as hypochlorous acid (HOCl) and inactivates lysosomal enzymes, iii) Pretreatment with Au(III) of a model protein antigen, bovine ribonuclease A (RNase A), induced novel antigenic determinants recognized by CD4+ T lymphocytes. Analysis of the fine specificity of these "Au(III)-specific" T-cells revealed that they react to RNase peptides that are not presented to T-cells when the native protein, i.e., not treated with Au(III), is used as antigen. The T-cell recognition of these cryptic peptides did not require the presence of gold. This finding has important implications for understanding the pathogenesis of allergic and autoimmune responses induced by gold drugs. Taken together, our findings indicate that Au(I) and Au(III) each exert specific effects on several distinct functions of macrophages and the activation of T-cells. These effects may explain both the desired anti-inflammatory and the adverse effects of antirheumatic gold drugs.
8273584 Interleukin-1 beta induces cytosolic PLA2 in parallel with prostaglandin E2 in rheumatoid 1993 We investigated the temporal relationship between the increase in enzymatic activity and protein of a high molecular weight (100 kDa), cytosolic PLA2 (cPLA2) in interleukin-1 beta (IL-1 beta)-treated rheumatoid synovial fibroblasts (RSF). Both of these responses increased according to a similar time-course which correlates with PGE2 production by these cells. In contrast, 14 kDa, secreted PLA2 (sPLA2), which was also produced by RSF, was not affected by IL-1 beta treatment. These findings support that an augmentation of CPLA2 activity, caused by an induction of cPLA2 protein, rather than sPLA2, is temporally associated with increased PGE2 production in IL-1 beta-treated RSF.
8099856 The B cell repertoire of patients with rheumatoid arthritis. Frequencies and specificities 1993 Jun Using a potent in vitro limiting dilution culture system, we have activated human peripheral blood B cells to proliferate and to differentiate into antibody-secreting cells (ASC). Under these conditions 25-100% of B cells are clonally expanded and produce IgM, IgG or IgA. Culture supernatants were tested for antibodies binding to human IgG-Fc fragments (RF), the 65-kD heat shock protein of Mycobacterium bovis (hsp60), human collagens type I, II, IV, V, transferrin, lactoferrin, albumins, and gelatine. All blood samples contained precursors of ASC (p-ASC) able to produce IgM binding to these antigens in frequencies above 0.03% of B cells. Most interestingly, a significant difference exists between rheumatoid arthritis (RA) patients and controls, concerning the relative frequencies of p-ASC able to produce monospecific or multireactive RF. Whereas most p-ASC(RF) in RA patients are monospecific (mean ratio 3.7), most p-ASC(RF) in healthy control persons are cross-reactive with at least one of five other antigens tested (mean ratio 0.2). The data suggest a disease-specific expansion of p-ASC committed to the production of monospecific rheumatoid factors.
8441166 IgA anti-dsDNA antibodies in systemic lupus erythematosus: occurrence, incidence and assoc 1993 Jan The relationship between IgA anti-dsDNA antibodies and systemic lupus erythematosus (SLE) disease activity was investigated. IgA anti-dsDNA antibodies were measured using ELISA techniques. Elevated serum levels of IgA anti-dsDNA antibodies were detected in 51% of the patients with SLE (n = 57) and 8% of the diseased controls (n = 214). The presence of IgA anti-dsDNA antibodies was associated with kidney and joint abnormalities, with hypocomplementemia and with circulating immune complexes. We conclude that increased levels of IgA anti-dsDNA antibodies are associated with disease activity in patients with SLE.
7901895 Soluble intercellular adhesion molecule-1 (ICAM-1) antigen in patients with rheumatoid art 1993 Nov Intercellular adhesion molecule-1 (ICAM-1), a member of the immunoglobulin supergene family, is known to play an important role in inflammatory diseases. Using a previously developed enzyme-linked immunosorbent assay (ELISA) with two monoclonal antibodies (MoAbs) against human ICAM-1, levels of soluble ICAM-1 (sICAM-1) were measured in sera from patients with collagen diseases and in synovial fluids (SF) from patients with rheumatoid arthritis (RA). Although the results did not demonstrate that RA and other collagen diseases, as a group, had significantly higher levels of sICAM-1 in sera as compared with healthy controls, 21 of 138 cases (15%) with collagen diseases and 11 out of 57 patients (19%) with RA clearly showed higher levels of sICAM-1 in the sera. Comparisons between RA patients of radiological stages I and II and between stage I and other stages showed significantly higher levels of sICAM-1 in the sera of patients in the latter stages. RA patients with vasculitis and/or pneumonitis showed significantly higher levels of sICAM-1 than those without vasculitis or pneumonitis. Significant correlations were demonstrated between sICAM-1 and the factors IgG-RF, IgM-RF, erythrocyte sedimentation rate (ESR) and TNF-alpha in sera of RA patients. In addition, it was noted that the levels of sICAM-1 in SF were as high as those in the sera of patients with RA.
7871333 A radioreceptor assay for TNF alpha-binding proteins. 1994 A radioreceptor assay for tumour necrosis factor alpha (TNF alpha)-binding proteins was development that is suitable for use with synovial fluids and sera. This assay, an alternative to the commonly used enzyme-linked immunosorbent assays (ELISAs), is not specific for soluble tumour necrosis factor alpha receptors (sTNF-R), but detects any molecules that might compete with TNF alpha for receptor binding. It also detects molecules that might bind TNF alpha and thereby interfere with subsequent binding to receptor. In a preliminary study, the assay was used to determine levels of TNF alpha-binding activity in a test group of synovial fluids from patients with rheumatoid arthritis (RA), osteoarthritis (OA) or psoriatic arthritis (PA). Levels of binding activity were much higher than those reported for sTNF-R alone in other studies [1, 2]. Our results indicated that there may be other molecules associated with the inflamed synovium that can interfere with the binding of TNF to its receptors and so attenuate its effect in diseases such as RA.
8792509 Insufficiency fractures of the pubic ramus. 1996 Jun Seven elderly women with insufficiency fractures of the pubic ramus are described. The predisposing factors for this condition were osteoporosis, rheumatoid arthritis, renal failure, prolonged corticosteroid treatment, pelvic irradiation, and mechanical changes after hip surgery. The clinical presentation included progressive inguinal pain, limping, and inability to walk. Because initial radiographs were diagnostic only in four cases, bone scintigraphy and computed tomography were necessary to confirm the diagnosis and detect additional fractures. In most patients, bed rest, non-weight-bearing ambulation, symptomatic treatment, and therapy for osteoporosis resulted in rapid improvement, and long-term follow-up showed complete or partial recovery. In one case, no recovery was achieved because of noncompliance with treatment. Insufficiency fracture of the pubic ramus should be suspected in cases of unexplained inguinal or hip-area pain and inability to walk in the elderly. The clinical suspicion should be supplemented by radiological investigation. Bone scintigraphy and computed tomography are useful means for early and accurate diagnosis. The risk factors for this condition should be identified and treated. If therapy is initiated early and pursued, this type of fracture has a benign outcome.
7616270 Surgical management of atlantoaxial nonunions. 1995 Aug Sixteen patients referred for atlantoaxial fixation failures were treated surgically with revision procedures during the past decade. Of these 16 patients, atlantoaxial instability occurred because of rheumatoid arthritis in five, as odontoideum in seven, transverse ligament disruption in two, and odontoid fracture nonunion in two. The 16 individuals (10 men, six women; mean age 43.7 years; age range 20-77 years) had undergone a total of 20 C1-2 internal fixation procedures that failed. Surgical strategies for definitive revision of the nonunions in these 16 subjects included 10 rigid internal fixations with transarticular screws, three revised C1-2 fixations with autogenous bone struts and wire or cables, and three extended fixations with occipitocervical instrumentation. Autogenous grafts were used in all revisions. A postoperative halo brace was used in five individuals with osteoporotic bone; all patients wore a restrictive postoperative cervical orthosis. Postoperatively, 15 patients (94%) had a stable construct (mean follow up 35 months; range 12-79 months), which included 13 osseous unions and two stable fibrous unions. One patient had nonunion; he fractured his anterior C1-2 transarticular screws 2 years postoperatively. He had occipital radicular pain without myelopathy but refused further surgery. Atlantoaxial pseudarthroses were effectively treated by addressing the pathological, biomechanical, and technical reasons for failed fusion. Successful fusion after reoperation was improved by using autologous bone grafts, adequately controlling atlantoaxial motion (with rigid transarticular screws internally or externally with a halo vest), compressing the bone grafts between the arches of C-1 and C-2 with wire cables, meticulously preparing the fusion bed, and by optimizing the pharmacological and clinical parameters to promote bone healing.
1356636 The induction of arthritis in mice by the cartilage proteoglycan aggrecan: roles of CD4+ a 1992 Oct 15 Peripheral arthritis is produced in BALB/c mice after hyperimmunization with the cartilage proteoglycan aggrecan (PG). Adoptive transfer studies have suggested the roles of T cells including CD8+ T cells in the disease process. To evaluate the roles of CD4+ and CD8+ T cell subsets in vivo in the induction of this disease by immunization, PG-immunized mice were treated with isotype-controlled rat IgG2b monoclonal anti-CD4 or anti-CD8 antibodies, or were left untreated. CD4+ T cell depletion resulted in total inhibition of the disease with markedly decreased anti-PG antibody responses. CD8+ T cell depletion, however, significantly enhanced the severity of the disease without affecting peak anti-PG antibodies, as compared to the control mice. These results demonstrate a crucial role for CD4+ T cells in the pathogenesis of this disease. However, CD8+ T cells do not seem to be required for the induction of arthritis by immunization but instead may play an immunoregulatory role.
8099341 Demonstration of CD13/aminopeptidase N on synovial fluid T cells from patients with differ 1993 Jan Cytofluorometric analysis was performed to characterize the immunophenotype of lymphocytes of the synovial fluid (SF) and the peripheral blood (PB) from patients suffering from juvenile chronic arthritis (JCA) or rheumatoid arthritis (RA). The most obvious difference could be found in expression of the surface protease aminopeptidase N (AP N/CD13). Whereas monoclonal antibodies specific to CD13 failed to reveal surface expression on lymphocytes of the PB; 63 +/- 15% of SF T cells gave positive staining for CD13 using Leu-M7. No correlation between CD13 expression and joint disease could be found in patients who had different types of inflammatory joint effusions. CD13 expression of T cells was also found in synovial tissue and inflammatory serous cavity effusions. Fixation of T cells revealed the presence of intracellular CD13 antigen already located in the PB T cells of healthy individuals. Induction of CD13 expression on PB T cells could be demonstrated after incubation with Con A/IL-2 or SF from patients with RA. Our findings suggest a role for AP N as a new activation-associated molecule of T lymphocytes.
7799335 Human mucosyl lymphocyte marker expression in synovial fluid lymphocytes of patient with r 1994 Sep OBJECTIVE: Human mucosyl lymphocyte marker (HML-1) antigen is an activation antigen and adhesion molecule of the beta 7 integrin family, which is generally restricted to T cells found in the intestinal epithelium. Expression of the membrane antigen as defined by the monoclonal antibody HML-1 was studied on peripheral blood (PB) lymphocytes and synovial fluid (SF) lymphocytes in 10 patients with rheumatoid arthritis (RA) and in a control group of patients with osteoarthritis (OA). METHODS: Double fluorescence activated flow cytometry was used to assess HML-1 expression with T cell subtype antigens (CD3, CD4, CD8) or activation markers interleukin 2 receptor (IL-2R) (CD25), HLA-DR, and lymphocyte function associated antigen (LFA-1) (CD11a) were assessed by flow cytometry. RESULTS: HML-1 antigen expression in PB lymphocytes of patients with RA (7.3%) was found to be comparable to the control group (6.4%). In contrast, 25.4% (range 14-43%) of SF lymphocytes expressed HML-1 antigen, compared to 13.6% of SF lymphocytes in patients with OA (p < 0.001). In RA, 62% of HML-1 positive cells from SF lymphocytes were the CD8 subtype, compared to 10.6% of PB lymphocytes (p < 0.003), and 18% of control SF lymphocytes (p < 0.05). Furthermore, HML-1 antigen and HLA-DR antigen were coexpressed in 75% of RA SF lymphocytes compared to 29.6% of control SF lymphocytes (p < 0.01). In contrast, coexpression of LFA-1 and the Il-2R did not differ from that of control. CONCLUSION: We describe overexpression of the adhesion molecule HML-1 in SF lymphocytes of patients with RA, preferentially in the CD8 subset. These results suggest a similarity between the expression of activation antigens in SF lymphocytes of patients with RA and T lymphocytes present in the intestinal epithelium.
8485559 Calprotectin in patients with systemic lupus erythematosus: relation to clinical and labor 1993 Feb Calprotectin (L1) is a granulocyte and monocyte cytosolic protein released during activation of these cells. The plasma level of L1 has been shown to be a good marker of disease activity in rheumatoid arthritis. In this cross-sectional study of 100 patients with systemic lupus erythematosus (SLE), the serum level of L1 was found to be higher in patients than in matched controls (3661 micrograms/l versus 1051 micrograms/l; P < 0.001). The serum level of L1 was the only laboratory parameter with significant association to the disease activity index SLEDAI (r = 0.28; P < 0.01). Furthermore, the serum level of L1 was significantly higher in SLE patients with anti-DNA antibodies compared to patients without anti-DNA antibodies (4501 micrograms/l versus 3279 micrograms/l; P = 0.01). SLE patients with arthritis had higher serum levels of L1 than patients without arthritis (7652 micrograms/l versus 2811 micrograms/l; P < 0.01), indicating that the serum level of L1 also reflects arthritis activity in SLE.
1319430 Atypical peripheral neuropathies. 1992 May Systemic disease and metabolic imbalance may be associated with peripheral nerve focal compressive neuropathies. The nerve may be primarily involved, or symptoms may result from chronic tenosynovitis or synovitis. We review the more commonly occurring compressive neuropathies associated with underlying systemic disorders.
8257775 Extracellular phospholipase A2 expression and inflammation: the relationship with associat 1993 Aug Human non-pancreatic PLA2 has been the object of intense scrutiny for a relatively short period of time. Its role in physiology remains enigmatic. While PLA2 may serve to remodel or remove peroxidised or senescent phospholipids, the enormous magnitude of its upregulation during infectious or inflammatory episodes is consistent with a role in host defense. However, the nature of this role remains elusive. Attempts to relegate this enzyme to the genre of acute phase reactants have not been helpful in unravelling its role. Difficulty in obtaining adequate amounts of native snp-PLA2 prior to the availability of recombinant snp-PLA2 led to the widespread use of snake venom homologs, particularly in studies of the biology of PLA2. This review has underscored the pitfalls inherent in that approach given the major differences between some venom PLA2s as compared to snp-PLA2. In addition, it bears reiterating that the complex composition of venom allows for potentiation of PLA2 activity by other constituents present in venom. Whether human host defense networks employ this interactive strategy is largely unknown. Nonetheless, in spite of these reservations, some very compelling data have emerged in recent years implicating snp-PLA2 in the initiation or potentiation of local and systemic inflammatory processes. These include sepsis and associated acute lung injury as well as inflammatory arthritides, with rheumatoid arthritis as the prototype. The mechanisms of snp-PLA2 homeostasis are considerably better understood, and it has become apparent that snp-PLA2 is an integral part of a larger network of proinflammatory cytokines, growth factors and lipid mediators. The interrelationship between the functions of secretory and cytosolic PLA2s remains to be defined. A number of selective PLA2 inhibitors have been identified which will allow for discrimination between the actions of these classes of PLA2. The availability of synthetic inhibitors in conjunction with endogenous modulators of PLA2s will shift the biology of PLA2 from the realm of the inferential to that of the mechanistic.