Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
316826 Serum proteins--transferrin, ceruloplasmin, albumin, alpha 1-acid glycoprotein, alpha 1-an 1979 Nov Serum levels of carrier proteins, transferrin, ceruloplasmin and albumin were determined in patients with rheumatic disorders, along with serum levels of acute phase proteins, ceruloplasmin, alpha 1-acid glycoprotein and alpha 1-antitrypsin. Depressed levels of transferrin occurred in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Albumin was reduced in SLE and RA men. Acute phase reactants which are protective in inflammation were elevated in RA, osteoarthritis (OA), gout, pseudogout (PsG), and SLE. All of these rheumatic disorders show biochemical changes compatible with systemic inflammatory disease including gout and PsG which are considered local disorders and OA which is considered noninflammatory arthritis.
6348931 [Significance of anti-centromere antibodies. Clinical value]. 1983 Apr The authors report 38 cases of patients with antinuclear antibodies directed against the centromere of the chromosomes. These were 32 cases of scleroderma, 2 cases of Raynaud's syndrome, 2 cases of rheumatoid arthritis, 1 case of polymyositis and 1 case of disseminated lupus erythematosus. In the cases of scleroderma, anti-centromere antibodies were detected in 54 p. cent of cases of Crest syndrome, for which they are a good laboratory marker; they were found more rarely in case of sclerodactyly (26 p. cent of cases) and acrosclerosis (14 p. cent of cases) and not at all in cases of localized scleroderma, diffuse scleroderma or eosinophilic fasciitis. Anti-centromere antibodies may be the only antinuclear antibodies in these patients. They can be detected using rapidly dividing cell cultures.
7142320 Simultaneous determination of tolmetin and its metabolite in biological fluids by high-per 1982 Oct 8 A highly sensitive and selective high-performance liquid chromatographic assay has been developed for the separation and quantitation of tolmetin and its major metabolite in human biological fluids, viz. plasma, urine and synovial fluid. Analysis of plasma and synovial fluid required only 0.5 ml of the sample. The sample was washed with diethyl ether and extracted with diethyl ether-chloroform (2:1). The extracted compounds were injected onto a reversed-phase column (RP-2) and absorbance was measured at 313 nm. The standard curves in plasma were found to be linear for both tolmetin and the metabolite at concentrations from 0.04 to 10.0 microgram/ml. Urine samples (0.5 ml) were diluted (1:1) with methanol containing the internal standard and were directly injected onto the reversed-phase (RP-2) column. Standard curves of tolmetin and metabolite in urine were linear in the range 5-300 microgram/ml. Serum and synovial fluid concentrations of tolmetin and its metabolite in patients receiving multiple doses of tolmetin sodium were determined using the assay procedure.
6609699 Autoantibodies to small nuclear ribonucleoproteins. A strong association between anti-SS-B 1983 Dec The heterogeneity within multisystem autoimmune disease was evaluated according to the presence of antinuclear antibodies to ribonucleoproteins and the HLA-A1, B8, DR3 phenotype. Patients with various multisystem autoimmune diseases were tested by a highly sensitive radioimmunoassay for autoantibodies to the small nuclear ribonucleoproteins known as SS-B (La) and ribonucleoprotein (RNP), and HLA phenotypes were determined. The 210 patients included 64 with systemic lupus erythematosus (SLE), 11 with "atypical SLE", 41 with Sjögren's syndrome, 22 with mixed connective tissue disease (MCTD), 21 with rheumatoid arthritis (RA), 16 with primary biliary cirrhosis (PBC) and 35 with autoimmune chronic active hepatitis (A-CAH). Anti-SS-B (La) was present in high frequency in Sjögren's syndrome and was strongly associated with HLA-A1, B8, DR3. Anti-RNP was detected predominantly in MCTD and had no association with HLA-A1, B8, DR3. There were sharply defined serological and genetic differences between primary Sjögren's syndrome and Sjögren's syndrome associated with RA. Anti-SS-B (La) was present in 70% of patients with primary Sjögren's syndrome but in none with Sjögren's syndrome with RA, and the respective frequencies of HLA-A1, B8, and DR3 were 88%, 94% and 75% in the former compared with 38%, 29% and 14% in the latter. Thus primary Sjögren's syndrome differs immunogenetically from Sjögren's syndrome with RA. There was a notable absence of anti-SS-B (La) in PBC, an autoimmune disease associated with the Sjögren's syndrome. These findings illustrate the value of studying immunological and genetic markers in detecting heterogeneity within groups of diseases whose symptoms cannot be distinguished clinically.
315611 [Changes in blood calcium, phosphorus and alkaline phosphatase levels in rheumatoid polyar 1979 Jun Albuminemia, calcemia, phosphoremia and alcaline phosphatasemia were measured in three groups of 52 subjects each : rheumatoid arthrits, inflammatory rheumatisms other than rheumatoid arthritis and lumbarthrosics serving as a reference group. Calcemia and albuminemia were significantly lower in patients suffering from rheumatoid arthritis, whose calcemia corrected in relation to albuminemia is, on the other hand, normal : the increase in corrected calcemia pointed out by Kennedy, was not noted. Corrected calcemia was also normal in ankylosing spondylitis, but it was significantly higher in polymyalgia rheumatica. Phosphoremia was shown to be normal but alkaline phosphatases were higher than normal in the three groups.
6969593 Serologic subsets in systemic lupus erythematosus: an examination of autoantibodies in rel 1980 Nov A search for anti-Ro or anti-nRNP antibodies by precipitin analysis among a population of 64 patients with systemic lupus erythematosus (SLE) or mixed connective tissue disease was undertaken. The 25% of SLE patients with anti-Ro did not have any distinct clinical features, compared to patients without anti-Ro or to anti-nRNP patients with SLE or mixed connective tissue disease. However, these patients did have a significantly greater frequency of rheumatoid factor (80%). Most importantly however, patients with anti-Ro had a significantly increased frequency of HLA-B8 (81%) and HLA-DRw3 (100%) compared to patients with anti-nRNP (B8--29%; DRw3--33%) or SLE patients without such antibodies (B8--41%; DRw3--25%). These data suggest the existence of a specific immune response gene for Ro close to the D region of the major histocompatibility complex.
7084291 Fenbufen in patients with gastric intolerance. 1982 Forty-one patients with inflammatory or degenerative arthritis and a history of gastric disturbance on other non-steroid anti-inflammatory drugs, or of peptic ulceration were treated with fenbufen 600-1200 mg dialy, and followed up for 3-17 months in an open study. Twelve patients withdrew because of lack of effect of the drug on the arthritic symptoms. Four patients withdrew because of non-gastrointestinal side effects. Three patients withdrew because of continuing dyspepsia. Twenty-two patients continued on fenbufen without dyspepsia or evidence of gastro-intestinal bleeding for 3-17 months (mean 8.3 months). These results suggest that fenbufen can be tolerated by patients with a history of gastro-intestinal disturbance on other NSAIDs, and that a larger controlled study would be warranted.
7226634 UCLA anatomic total shoulder arthroplasty. 1981 Mar The UCLA total shoulder arthroplasty was designed to mobilize the shoulder joint in order to permit normal anthropometric range of motion and durable long-term fixation of the components. The prosthesis is fundamentally nonconstrained for the usual arthritic conditions, currently with four sizes of femoral and glenoid components. For patients with deficient and irreparable rotator cuffs, additional restraint may be effected by using a superior glenoid subacromial rim. The first 11 patients have been followed for 1 1/2 to 3 1/2-years; relief of pain has been complete in all but two patients. The function and range of motion results were related to the status of the rotator cuff; five patients achieved excellent results, including two with osteoarthritis who had near normal function. Patients with deficient rotator cuffs achieved functional use of the extremity but without full range of motion. Functionally, in addition to the five patients who were rated excellent, two were rated as being good, three fair, and one poor. In addition to five with excellent range of motion, there were three good and four fair ratings. Two patients, one with grossly deficient musculature caused by a gunshot wound and a second who was posttrauma required revision surgery with a subacromial glenoid prosthesis. This prosthesis is now frequently utilized if muscles and rotator cuff are deficient at the primary surgery, in order to provide additional restraint. Determination of the efficacy of hooded components will require further follow-up. The additional size ranges and components together with improved instrumentation have greatly facilitated recent surgery.
2410510 Detection of a neoantigen on human C3bi and C3d by monoclonal antibody. 1985 Sep A neoantigen was detected on human C3bi and C3d by using the monoclonal antibody (MoAb) 130. The antibody bound to EC3bi and EC3d cells but not to EC3b. Although highly purified C3bi or C3d strongly inhibited the binding of the antibody to EC3d, highly purified C3c had no such effect. Native C3, C3b, or C3(H2O) inhibited this binding only weakly. The neoantigen was also detected in serum after activation with zymosan or heat-aggregated IgG, and it was found bound to the aggregated IgG and zymosan particles. Plasma samples from patients with immunologic disorders were tested for this neoantigen, and 25 out of 43 samples tested were found to have levels of neoantigen corresponding to 2 to 11.5% complement activation, whereas 13 out of 14 normal donor plasmas contained amounts of neoantigen indicating much less than 1% complement activation.
6777453 [The use of laser nephelometry for the determination and computer-assisted calculation of 1980 Nov We report a laser-nephelometric procedure for the determination of the concentration of fibronectin in various human and animal body fluids. The method is precise (CV intra-assay 2.1%), sensitive (the detection limit is 1.2 mg/l fibronectin), rapid, relatively simple and can be totally mechanized. By use of programmable calculators an electronic evaluation of the scattered light signals is possible. The antigen concentrations determined both by laser nephelometry and radial immunodiffusion show a coefficient of correlation of r = 0.859. In plasma of healthy men the mean concentration of fibronectin is 291 mg/l; women have a significant lower concentration of 259 mg/l. Increased levels of plasma fibronectin were found in patients with carcinomas of the female genital tract and Morbus Crohn. Synovial fluids obtained from inflammatory joint diseases contain significantly higher concentrations of fibronectin (318 mg/l) than those from non-inflammatory joints. The range of concentration of fibronectin in seminal plasma is similar to that in blood plasma, but a large inter-individual variation was observed. Extremely low antigen concentrations (0.41 mg/l) were determined in normal liquor cerebrospinalis, but under pathological conditions a significant increase occurs, which correlates strongly with the cell count. Low levels of fibronectin (16 mg/l) were also found in amniotic fluid at the end of pregnancy.
7112200 Total hip arthroplasty: review of long-term results in 185 cases. 1982 Aug Review of 185 consecutive Muller total hip arthroplasties five to nine years after operation showed that 14 patients had died and that three deaths were directly related to the surgery. Of these, 37 patients (54 hips) could not be located and were excluded. Another patient, nonambulatory for an unrelated cause, was also excluded. A total of 126 hips in 104 patients were available for clinical and roentgenographic examinations with a minimal follow-up of five years. The final result was excellent in 70%, good in 10%, fair in 5%, and poor in 15%. One deep infection required removal of the prosthesis. There was no sciatic nerve injury. Five hips dislocated postoperatively and six others had recurrent subluxation. Replacement of the acetabular component was required in four hips, three because of loosening and the other for malposition in association with paraparesis. Trochanteric osteotomy was done in nine hips and four failed to unite. There was roentgenographic evidence of femoral component loosening in 28% of the hips and 8% required replacement. Poor cement filling and varus positioning of the femoral stem contributed to loosening.
6503218 [Fibronectin]. 1984 Oct 15 Fibronectin is a dimeric glycoprotein with a molecular weight of 440,000. It is a soluble constituent of plasma and other body fluids and a fibrillar matrix protein of connective tissue. The two components are structurally similar and convertible. The possibility of multiple molecular interactions gives rise to a variety of biological functions. The regulation of cell growth and the reduced shedding of fibronectin from malignant cells raises the question as to whether fibronectin is valid as a tumour marker. In wound healing and chronic inflammation fibronectin serves as a scaffold for the formation of collagen. As opsonic protein it maintains reticuloendothelial function. Especially in shock, fibronectin may become the limiting factor of unspecific host defence mechanisms. The value of a substitution therapy will be discussed.
7095824 The origin of type A synovial lining cells. 1982 Apr Type A synovial lining cells resemble macrophages in their ultrastructure. Type B lining cells, in contrast, resemble tissue fixed synthetic cells such as fibroblasts. Although cells with intermediate features are well recognised, recent evidence suggests that types A and B cells have different origins. Experiments on mouse radiation chimeras suggest a bone marrow derivation for the type A cells, but not for the type B. Esterase activity, surface Ia, and immunoglobulin receptors have been demonstrated in relation to a proportion of lining cells. It seems reasonable at the present time to consider type A lining cells as belonging to the Mononuclear Phagocyte System.
1238328 [Anti-inflammatory action of 2-(2-fluoro-4-biphenylyl) propionic acid (flubiprofen]. 1975 Sep 2-(2-fluoro-4-biphenylyl) propionic acid (flurbipofen, FP-70), a newly synthesized anti-inflammatory agent, was examined for its effects and then compared with the actions of other standard drugs. Inhibition of capillary permeability in mice: the activity of FP-70 was 7.8 times as potent as ibuprofen (IP), 61 times that of acetylsalicylic acid (AS), 5.7 times that of indomethacin (IM) and 25 times that of phenylbutazone (PB). Inhibition of carrageenin-induced edema in rat paw: the activity of FP-70 was 52 times as potent as IP, 250 times that of potent as AS, 14 times that of potent as IM and 110 times that of potent as PB. Inhibition of heat-induced coagulation of BSA: the activity of FP-70 showed the marked effects much the same as IP. In adrenalectomized rat, FP-70 was also effective. Inhibition of the ultra-violet erythema in guinea-pigs, the activity of FP-70 was 26 times as potent as IP, 790 times that of AS, 25 times that of IM and 68 times that of PB. Regarding the inhibition of CMC induced pouch in rats, the potency of FP-70 was to the same degree as that of predonisolone. In adjuvant induced arthritis in rats, FP-70 reduced and cured inflammatory syndromes and activity was the same or more effective than that of IM. From these results, FP-70 appears to be a most potent nonsteroidal anti-inflammatory agent.
6999159 The detection of double stranded DNA antibody using human metaphase chromosomes. 1980 May Double stranded native DNA (dsDNA) antibody detection is important in the diagnosis and management of patients with Systemic Lupus Erythematosus (SLE). Current radioimmunoassay and haemagglutination assays for DNA antibodies are technically complicated or show considerable inter-laboratory variation. A simple inexpensive indirect immunofluorescence method using fixed human metaphase chromosomes for DNA antibody estimation is described. The method has been compared with the Farr radioimmunoassay and Crithidia luciliae techniques. The metaphase test showed 100% correlation with a positive Farr assay in 38 of 373 routine DNA antibody estimations. Simultaneous testing using Crithidia showed 84% correlation, indicating greater sensitivity of the metaphase method. Enzyme treatment of metaphase and Crithidia substrate abolished reactivity on DNAase treated substrate alone, and DNA specific fluorescent staining further confirmed metaphase substrate specificity. The metaphase test appears simple, specific, of greater sensitivity, easily read, and can be utilized in large or small laboratories to determine DNA antibodies and their subclasses.
6813492 Comparative pharmacology and biological effects of different gold compounds. 1982 Jul Auranofin's (AF) physical, chemical, pharmacological, and pharmacokinetic properties differ from those of gold sodium thiomalate (GSTM). AF is lipid soluble, monomeric, nonconductive and is not a potent sulfhydryl reagent. In further contrast to GSTM, AF gold is orally absorbed, exhibits protracted blood levels, is bound to cellular elements of the blood, excreted mainly in the feces, and exhibits less tissue retention. AF is more effective in acute inflammatory models and is a potent inhibitor of lysosomal enzyme release, antibody-dependent cellular cytotoxicity, and superoxide production. AF can suppress antibodies produced in adjuvant arthritic rats and those involved in cytotoxicity reactions; whereas, GSTM is ineffective or immunoenhancing. AF is more effective in stimulating abnormalized cell-mediated immunity. In conclusion, AF is a unique oral chrysotherapeutic agent which can affect cellular and immunopathological events involved in the perpetuation of inflammation and tissue damage.
6453425 Musculoskeletal syndromes associated with malignancy. 1981 Feb Evidence has been presented supporting a causal relationship between malignancies and musculoskeletal syndromes. This discussion has dealt primarily with lesser known relationships, more common associations such as hypertrophic osteoarthropathy and dermatomyositis being reviewed elsewhere. The ones discussed herein closely mimic primary connective tissue diseases and offer an insight into the study of the pathogenesis of these primary diseases. In view of the natural history of malignant disease, the hope for such patients arises from the physicians early diagnosis and treatment of the underlying malignancy. Early diagnosis and treatment may in turn be entirely dependent on the physician's awareness of a musculoskeletal syndrome being the presenting feature of an otherwise occult neoplasm. Several connective tissue syndromes appear to predispose to the development of malignancy, and increasing evidence suggests that this development of malignancy may be further enhanced by immunosuppressive therapy.
6301748 Collagens act as ligands to stimulate human monocytes to produce mononuclear cell factor ( 1982 Nov Blood mononuclear cells from patients with rheumatoid arthritis produce the lymphokine, leukocyte inhibitory factor (LIF) in response to collagens in vitro, and blood monocytes release prostaglandins (PGE2) and a factor, mononuclear cell factor (MCF) which stimulates collagenase and PGE2 production by cultured synovial cells. We therefore examined the effect of collagens on the production of PGE2 and MCF. Blood mononuclear cells from 6 patients with rheumatoid arthritis and 6 normal subjects were cultured in native human types I, II, or III collagen-coated tubes, or with streptokinase-streptodornase (SK-SD), and the supernatant media derived from these cultures analyzed for the presence of MCF, PGE2, and LIF. Types II and III collagens, as well as SK-SD, markedly stimulated MCF production by the cells from all 12 subjects (MCF activity, expressed as a mean stimulation index (SI) +/- SEM, was 43 +/- 12 for type II, 33 +/- 7 for type III, and 37 +/- 23 for SK-SD). Type I collagen was less stimulatory (mean SI 10 +/- 7). Cells from the patients with rheumatoid arthritis, but not the normal subjects, produced LIF in response to types II or III collagens but not to type I collagen. PGE2 production by blood mononuclear cells paralleled that of MCF, although abrogation of PGE2 release with indomethacin did not reduce MCF production. alpha chains purified from denatured collagens also stimulated MCF production. Using cells from patients with rheumatoid arthritis, type II collagen stimulated production of all three factors in the presence of polymyxin B or fibronectin-depleted serum, suggesting, respectively, that neither endotoxin nor fibronectin were responsible for their generation. Monocytes, purified from normal blood by an adherence technique, but not lymphocytes depleted of monocytes, released MCF and PGE2 when cultured with type II collagen. These results demonstrate that collagens can act as ligands to stimulate monocytes, as well as antigens to stimulate sensitized lymphocytes, to produce soluble factors that may contribute to the destruction of connective tissue.
82275 [Disseminated lupus erythematosus: an analysis of organ involvement]. 1978 Nov 18 The spectrum of involvement of organs in 70 patients with systemic lupus erythematosus has been assessed in a prospective study. All patients were admitted to hospital electively for 2 days and a complete clinical and laboratory assessment protocol completed. The overall mean observation period was 29 months. Widespread multisystem involvement was found in every patient. Subclinical abnormalities of respiratory and cerebral function were common. A more conservative approach than has been generally recommended was used for the management of systemic lupus erythematosus and is justified by 5-year survival of 98%.
2996929 Stimulation of procollagenase synthesis in human rheumatoid synovial fibroblasts by mononu 1985 Oct 21 In order to define mechanisms regulating the synthesis of procollagenase in human rheumatoid synovial fibroblasts, the proteins synthesized by cultured cells were labeled with [35S]methionine. Labeled medium proteins were analyzed by SDS-PAGE directly and after immunocomplexing with a specific antibody to human fibroblast collagenase. Labeling of both the predominant form of the enzyme (Mr approximately 55 000) as well as a minor species (Mr approximately 61 000) was increased following incubation with the monokine, mononuclear cell factor/interleukin 1. The approximately 61 kDa form of the procollagenase appears to be a glycosylated form of the approximately 55 kDa precursor based on binding to Con A-Sepharose and decrease in the approximately 61 kDa form after culture in the presence of tunicamycin. Thus, mononuclear cell factor, homologous with interleukin 1, partially purified from monocyte conditioned medium increased incorporation of [35S]methionine into several medium proteins, including those complexed by the anticollagenase antibody. In the presence of mononuclear cell factor/interleukin 1, labeling of the procollagenase was increased 12-14-fold over control cultures incubated with medium alone. Therefore, one of the mechanisms involved in increase of collagenase activity in the medium of cultured synovial fibroblasts in the presence of mononuclear cell factor/interleukin 1 is a stimulation of enzyme protein synthesis.