Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3958085 | Measurement of penicillamine and N-acetylcysteine in human blood by high-performance liqui | 1986 Jan 24 | A rapid and precise high-performance liquid chromatographic assay for both N-acetylcysteine and penicillamine in blood samples is described using selective reductive electrochemical detection and a high-efficiency C18 reversed-phase column. The use of an internal standard compensated for changes in detector responses during a run and for variable sample recovery. The detection limits for N-acetylcysteine and penicillamine were 25 and 10 ng/ml, respectively, using 500-microliters blood samples. Reproducibility of measurement for both thiols was excellent. This method allows routine monitoring of blood levels and pharmacokinetic studies with N-acetylcysteine and penicillamine. | |
| 3516499 | Bone graft for tibial defects in total knee arthroplasty. | 1986 Apr | Twenty-four knees with bone grafts for tibial defects at the time of either primary or revision total knee arthroplasty were followed for three to six years. With 22 of 24 bone grafts, union and revascularization were seen and no clinical collapse was present. In two, nonunion occurred, accompanied by collapse in one. Failure was attributed to varus alignment of the leg in one (a medial condylar graft) and to insufficient preparation of the bony bed in the second (bleeding bone was not exposed). Evidence for incorporation of the grafts was obtained by tomogram, bone scan, and bone biopsy. Incorporation was present by six months, but the time to complete remodeling was not determined. A bone graft is recommended for tibial defect involving 50% or more of the bony support of either tibial plateau. A bone graft is indicated whenever a cement column under the prosthesis would measure more than 5 mm in height. | |
| 2942490 | Susceptibility of cartilage to damage by immunological inflammation. | 1986 | Injection of ovalbumin into subcutaneous air pouches prepared on the backs of rats previously sensitised to the antigen resulted in the induction of a small and transient accumulation of inflammatory fluid with a predominantly polymorph cell infiltrate. Challenge of pouches of appropriately sensitised rats with Bordetella pertussis vaccine, on the other hand, resulted in a larger and more prolonged accumulation of fluid and cells with a predominantly mononuclear presence. When intact homologous femoral head cartilage was implanted in these inflamed pouches proteoglycan loss was found to be not different from similar implants in non-inflamed pouches. Coating the cartilage with human heat-aggregated immunoglobulin G prior to implantation in air pouches was also found to be without effect on subsequent proteoglycan loss. | |
| 2363735 | Importance of the IgG isotype, not the state of glycosylation, in determining human rheuma | 1990 Jun | We investigated the influence of carbohydrate on the binding of human rheumatoid factors (RF) to the Fc fragment of IgG. The monoclonal RF studied were derived from the serum of patients with mixed cryoglobulinemia or from hybridomas generated from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus. Polyclonal RF were derived from patients with RA. The carbohydrate located on the Fc fragment, regardless of whether it contained different amounts of mannose or reduced amounts of galactose, or was removed, did not affect the binding of the RF. In contrast, the isotype of the Fc was found to be critical. Two groups of hybridoma RF could be delineated. One group bound preferentially to IgG1 and/or IgG2, and a second group (primarily from patients with RA) bound preferentially to IgG3 and/or IgG4. Our results indicate that the isotype of the Fc fragment, and not the extent of galactosylation, influences the binding of the RF. | |
| 2062256 | Is schizophrenia caused by excessive production of interleukin-2 and interleukin-2 recepto | 1991 Mar | Excessive production of interleukin-2 (IL-2) and IL-2 receptors (IL-2R) by gastrointestinal (GI) T-lymphocytes is hypothesized as the cause of schizophrenia. It is based on: 1) IL-2 given to human volunteers can cause all the symptoms of schizophrenia; 2) GI lymphocytes in nonhuman primates produce much more IL-2 and IL-2R when stimulated than peripheral blood lymphocytes; 3) the GI tract is the largest lymphoid 'organ' in the body. The hypothesis appears to: 1) explain the protective effect of rheumatoid arthritis on schizophrenia; 2) make mechanistically plausible the findings on wheat and schizophrenia; 3) be consistent with and explain many of the known immunological abnormalities in schizophrenia. | |
| 2966693 | The pharmacokinetics of etodolac in serum and synovial fluid of patients with arthritis. | 1988 May | The pharmacokinetics of etodolac have been evaluated in five patients with arthritis given 200 mg etodolac, twice daily, at 12-hour intervals, for 7 days. Albumin and total protein concentrations were markedly lower in synovial fluid than in serum, and etodolac free fraction was significantly higher. Etodolac readily penetrated into the synovial fluid, and in the postdistributive phase the concentration of free etodolac (i.e., the drug responsible for pharmacologic activity) remained higher than that in serum at all times. No differences in the half-life of etodolac elimination were noted. | |
| 1797027 | Changes in IgG glycoform levels are associated with remission of arthritis during pregnanc | 1991 Oct | It was found that the percentage of IgG-associated agalactosyl N-linked oligosaccharides (G0) falls during normal human pregnancy and rises to values higher than before conception following delivery (n = 10, 39-55 days after delivery). Serial bleeds from a normal pregnant woman showed a fall in the percentage G0 during gestation and a rapid rise post-partum. A similar study on a pregnant arthritic woman with a pathologically elevated percentage G0 also showed a fall in percentage G0 during pregnancy and a rapid rise post-partum. The changes in IgG glycosylation in the pregnant arthritic woman occurred simultaneously with the pregnancy-induced remission and post-partum recurrence of disease. A further seven pregnant women with rheumatoid arthritis were studied and analysis of their G0 values pre- and post-partum confirmed the result. In a further series of experiments using an animal model of rheumatoid arthritis, DBA/1 mice with collagen-induced arthritis were found to have elevated G0 levels compared with control mice. The percentage G0 was found to fall simultaneously with pregnancy-induced remission to the same value as non-arthritic pregnant mice. Post-partum recurrence of arthritis in these mice was also accompanied by a simultaneous and rapid rise in percentage G0. Pseudopregnancy did not result in a change in the percentage G0, confirming the effect of true pregnancy. Since the proportion of agalactosyl IgG is abnormally high in the serum of patients with rheumatoid arthritis these changes in IgG glycoform levels, or the factors which control them, may be related to the mechanisms underlying remission of arthritis in humans during pregnancy. | |
| 2503278 | Spontaneous and LPS-stimulated production of intracellular IL-1 beta by synovial macrophag | 1989 May | In the peripheral blood (PB) as well as the synovial fluid (SF) of rheumatoid arthritis (RA) patients significantly elevated levels of interleukin 1 beta (IL-1 beta) were determined compared to controls by means of a sensitive and specific ELISA (median values: 280 pg/ml and 325 pg/ml vs. less than 20 pg/ml). In 12-h cell cultures of adherent cells, significantly increased spontaneous intracellular IL-1 beta production was determined in SF macrophage (SFM phi) cultures of RA patients compared to PB monocyte (PBMo) cultures of controls (median values: 91.0 ng/10(6) cells vs. 31.5 ng/10(6) cells). However, secretion must be elicited by additional stimulation with lipopolysaccharide (LPS). Interferon-gamma (IFN-gamma) significantly inhibited the spontaneous intracellular IL-1 beta production in SFM phi 12-h cultures of RA patients. | |
| 2786386 | Spontaneously increased B cell growth factor and B cell differentiation factor activities | 1989 May | The presence of factors implicated in B cell proliferation and differentiation was studied in synovial fluid (SF) from patients with rheumatoid arthritis (RA) and from patients with ankylosing spondylitis (AS) and traumatic joint injury. Culture with Staphylococcus aureus Cowan I B cell blasts showed strong B cell growth factor (BCGF) activity in the SF from patients with RA. This BCGF activity was significantly greater than that found in SF from patients with traumatic joint injury and similar to that of patients with AS. The presence of B cell differentiation factor (BCDF) for IgM(mu) in the SF from patients with RA was also demonstrated and was significantly greater than that found in SF from patients with AS and traumatic joint injury. Moreover, a significantly increased BCDF for IgG(gamma) was also found in the SF from patients with RA compared with that observed in those patients with traumatic joint injury, which, however, was similar to that of patients with AS. | |
| 1927061 | [Rheumatologic and radiologic symptoms of dialysis-associated beta 2-microglobulin amyloid | 1991 May | beta 2-microglobulin amyloidosis is a major complication in chronic hemodialysis patients. Destructive arthropathy, spondylarthropathy, and carpal tunnel syndrome are clinical manifestations of beta 2M amyloid depositions within the joints, intervertebral discs, and tendon sheets. We have investigated the prevalence of beta 2M amyloidosis associated radiological joint lesions in a population of 175 patients on chronic hemodialysis. In 32 of 175 patients the diagnosis of amyloidosis arthropathy and spondylarthropathy was made by radiomorphological criteria. These 32 patients were asked about rheumatic symptoms (localisation and character of pain, synovitis, carpal tunnel syndrome, influence of dialysis membrane on pain) and examined clinically. Bilateral pain of the shoulders or wrists was complained by most of the patients. 24 of the 32 patients had signs of secondary hyperparathyroidism besides beta 2M-amyloidosis. 29 patients had a carpal tunnel syndrome, 23 of whom had to be operated. beta 2M-amyloid was histochemically demonstrated in all of these 23 cases. Renal transplantation led to immediate pain relief in 3 out of 3 patients, a change of the dialysis membrane (high-flux membrane) improved chronic pain in the majority of patients. | |
| 2702773 | Demonstration of anti-idiotypic antibodies directed against IgM rheumatoid factor in the s | 1989 Jan | We have identified the presence of anti-idiotypic activity against IgMRF in the sera of RA patients. Only patients seropositive for IgMRF had significant levels of anti-idiotypic activity, while seronegative patients and normal volunteers did not. When this anti-idiotypic activity was affinity-purified from a single RA patient, two separate binding activities were identified. IgG antibodies were pepsin-digested to F(ab')2 fragments before affinity-purification to remove the Fc portion capable of binding to IgMRF. Anti-idiotypic F(ab')2 fragments of IgG were eluted from an IgMRF-Sepharose 4B column. These F(ab')2 bound preferentially to IgMRF bearing an idiotype recognized by the anti-idiotypic murine monoclonal 17.109. A second anti-idiotypic F(ab')2 was affinity purified using rabbit anti-human Fc antibody bound to Sepharose 4B. These eluted antibodies behaved as the internal image of IgG, binding five out of seven IgMRF's tested. The binding of both anti-idiotypic F(ab')2 was inhibited with human IgG. The presence of both IgMRF and anti-idiotypic antibodies directed against it in the sera of RA patients suggests that anti-idiotypic antibodies alone are not capable of inhibiting the production of rheumatoid factor. | |
| 3462903 | Genetic markers in rheumatoid arthritis. | 1986 | Genetic as well as environmental factors are believed to be of importance in the etiology of rheumatoid arthritis (RA). There are a number of previous studies of genetic markers in RA, but so far no genetic linkage and only a few associations have been found. Of the associations only one (with the HLA antigen DR4) appears to be well documented. In most previous association studies the patients have not been divided according to sex and family history of RA. In this investigation the HLA antigens A, B and DR and five serum protein systems (Bf, C3, Pi, Hp and Tf) were studied in patients with erosive RA, from northern Sweden. Special attention was paid to variations in the strength of associations according to sex and family history of polyarthritis. The following results were found: The frequency of the HLA antigen B27 was significantly increased in the North-Swedish population (16.6%) and among patients with a family history of polyarthritis (42.6%). In agreement with previous investigations a significantly increased frequency of the DR4 antigen was found in the RA patients. In the properdin factor B (Bf) system the S phenotype was found to be significantly increased in male patients and in patients with a family history of polyarthritis, a more severe form of RA and high titres of rheumatoid factor. No significant differences with respect to phenotype or gene frequencies were found in the C3 complement system. Thus, the association between RA and C3 found in previous investigations was not confirmed. A significant increase of rare alpha-1-antitrypsin (Pi) types (MS, MZ, MF and SZ) was found among RA patients. However, the increase concerned mainly Z heterozygotes and was more strongly pronounced among male patients. In the haptoglobin system a significant increase of the Hp2 gene and the Hp2-2 type was found among patients with a family history of polyarthritis, more pronounced among males. A significant increase of the transferrin gene C2 and of the C2 type was found among male RA patients, more pronounced among patients with a family history of polyarthritis. In 6 out of 8 gene loci studied significant associations were found, which is in agreement with a multifactorial etiology of RA.(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 3321379 | Proliferative activity of cells in the synovium as demonstrated by a monoclonal antibody, | 1987 | The presence of proliferating cells has been sought in the synovium of rheumatoid arthritic (RA) and osteoarthritic (OA) joints using the monoclonal antibody Ki67, which marks a nuclear antigen present in all stages of the cell cycle apart from Go. Synovia were studied from 21 RA and 14 OA cases using the indirect immunoperoxidase technique. Double-staining was performed on 18 RA and 17 OA synovia with the simultaneous labelling of lysozyme (muramidase) by the immuno-alkaline phosphatase method and with Ki67 by the indirect immunoperoxidase method. Most of the RA and OA synovia showed an absence of Ki67-positive cells in the intimal cell layer. Three RA and four OA synovia showed no more than ten proliferating cells in the whole of the intimal layer examined. Similar results were obtained when double-labelling was performed. Eight RA and six OA synovia showed the presence of occasional Ki67-positive cells in the intimal layer. The total number of intimal cells was measured for each histological section, and the proliferation index calculated as the percentage of total cells in the intimal layer showing Ki67-positive staining. This varied between 0.03% and 0.0033% (between 1:2800 and 1:30,000 cells). In contrast, there were plentiful Ki67-positive cells present in the lymphocytic infiltrate and around blood vessels in the RA synovia and in the synovial infiltrate, where present, in the OA cases.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3318428 | Long-term treatment of rheumatoid arthritis comparing nabumetone with aspirin. | 1987 Oct 30 | This report summarizes the results of a 17-investigator multicenter six-month randomized double-blind parallel group study. The safety and efficacy of nabumetone 1,000 mg taken at bedtime was compared with that of aspirin 900 mg four times daily in the treatment of adult patients with active class II or III classical or definite rheumatoid arthritis. Two hundred sixty-four patients were entered into the study. Two hundred fifty-seven (126 nabumetone and 131 aspirin) patients were evaluable for safety. Two hundred thirty-four (113 nabumetone and 121 aspirin) patients were evaluable for efficacy. There was significant improvement in each of six clinical measurements of efficacy in both treatment groups and little difference between groups. The somewhat greater improvement in articular index and duration of morning stiffness in the nabumetone-treated group did not reach statistical significance. There was an equal percentage of patient withdrawal for lack of efficacy in each group. Overall, the rate of patient withdrawal due to adverse experiences was greater (p = 0.01) for aspirin-treated patients. These experiences were usually dispepsia, abdominal pain, and tinnitus. It was concluded that nabumetone was an effective anti-inflammatory drug in the treatment of rheumatoid arthritis with less toxicity than aspirin. | |
| 3621599 | Studies of the sialylation and microheterogeneity of human serum alpha 1-acid glycoprotein | 1987 Jul 15 | The sialic acid content of alpha 1-acid glycoprotein (AGP) and its degree of microheterogeneity were investigated in AGP isolated from the pooled sera of patients with rheumatoid arthritis, or myocardial infarction or cancer (elevated AGP) or cancer (non-elevated AGP) and of healthy volunteers. Sialic acid was elevated in AGP preparations from the cancer groups and lowered in the preparation from the rheumatoid group. All preparations showed considerable charge heterogeneity by two dimensional polyacrylamide gel electrophoresis (2D-PAGE), but there was little evidence of molecular weight heterogeneity; the latter finding being also confirmed by peptide mapping studies. Each AGP preparation gave a different 2D-PAGE pattern; these differences were even more evident after partial desialylation of the samples when as many as fourteen different species could be identified. It is concluded from the sialic acid measurements and the 2D-PAGE study that the different preparations of AGP contain sialic acid in different carbohydrate structures. Using thin-layer electrofocusing (EF) and silver staining, characteristic AGP patterns could also be demonstrated after separating very small aliquots of unfractionated pooled and unpooled sera of the different groups. Therefore, EF measurements of AGP in serum may have a useful future role in clinical investigations. | |
| 2957788 | Phenotypes of T lymphocytes from peripheral blood and synovial fluid of patients with rheu | 1987 | Lymphocytes from peripheral blood (PB) and synovial fluid (SF) from 21 patients with rheumatoid arthritis (RA) and 18 patients with juvenile rheumatoid arthritis (JRA) were studied with respect to T cell phenotypes using monoclonal antibodies in a rosette assay. The percentage of HLA-DR positive T cells was counted in PB and SF using indirect immunofluorescence. Suppressor cell activity of T cells from PB and SF was investigated by measuring the immunoglobulin production by pokeweed mitogen (PWM) stimulated B cells mixed with T cells at various ratios. The mean T4/T8 ratio was significantly lower in SF than in PB of both RA and JRA patients (p = 0.0062 and p less than 0.0001 respectively). The mean percentages of HLA-DR positive T cells were elevated in SF compared with PB in both patients groups (p less than 0.03 and p less than 0.04 in RA and JRA patients respectively). Mean suppressor cell activity and helper cell activity of T cells from SF and PB of JRA patients was normal. Thus there seems to be a dichotomy between the number of T8+ cells and suppressor cell function in mononuclear cells from SF of patients with JRA. This indicates that a considerable proportion of the T8+ cells in the SF do not have suppressor functions. | |
| 3133151 | C3, Gm, and Pi polymorphisms in rheumatoid arthritis. | 1986 Jun | This paper reviews the associations between RA and three non-MHS genetic markers: C3, Gm, and Pi. There is no evidence to suggest that genes linked to C3 predispose to RA. However, there is evidence to suggest that genes on chromosome 14, linked to both Gm and Pi, do influence susceptibility to RA and further studies of this chromosome are indicated. | |
| 3606408 | [Basophilic line of the articular cartilage in normal and various pathological states]. | 1987 Apr | Epiphyses of long tubular bones in the man and animals of various age, as well as experimental material of the adjuvant arthritis, with special reference to the basal part of the articular cartilage have been studied by means of histological, histochemical and histometrical methods. The structural-chemical organization of the basophilic line (tidemark) of the articular cartilage ensures its barrier role and participation in regulating selective permeability. Reconstruction of the tidemark in the process of physiological ageing and in cases of the articular pathology is aimed to preserve its integrity and in this way a complete differentiation of the noncalcified and calcified structures is secured. Disturbance of the basophilic line results in changes of the articular selective permeability, in invasion of vessels and structural elements of the bone marrow, and in development of profound distrophic and destructive changes of the cartilage--in deforming artrosis. Deflations in the structural-chemical organization of the tidemark indicate certain disturbances in the state of the system articular cartilage--subchondral bone. These data can be of prognostic importance. | |
| 2143708 | Characterization of the binucleated giant cells generated in the autologous mixed leucocyt | 1990 Aug | Binucleated giant cells several times larger than lymphocytes or monocytes were generated in an autologous mixed leucocyte reaction (AMLR) independent of DNA synthesis in patients with rheumatoid arthritis (RA). The AMLR giant cells with multiple cytoplasmic granules were non-specific esterase-staining positive, phagocytic, non-adherent, HLA-DR+, CD11b+, CD14+, 4F2+, CDW29+, and anti-transferrin receptor positive, but negative for T, B, or NK markers. RA patients aged less than 60 years from more giant cells: 12.6 +/- 13.5% (n = 33) as compared with 0.4 +/- 1.5% in age- and sex-matched normals (n = 38, (P less than 0.001). More giant cells were seen over age 60 in both groups: RA 20.1 +/- 15.5% (n = 5) and healthy controls 3.0 +/- 3.2% (n = 8) (P less than 0.01). Neither disease activity nor treatment appear to influence the result in RA. The giant cells that are probably derived from monocytes in AMLR may explain the formation of the giant cells in rheumatoid granulation tissues. | |
| 2930263 | Raised serum IgG and IgA antibodies to mycobacterial antigens in rheumatoid arthritis. | 1989 Feb | Autoantigens cross reactive with mycobacteria are implicated in the pathogenesis of adjuvant arthritis in the rat, and there are reports of changes in the immune response to mycobacteria in human rheumatoid arthritis (RA). We have therefore examined the IgM, IgG, and IgA antibody levels to crude mycobacterial antigens and to two recombinant mycobacterial heat shock/stress proteins (65 kD and 71 kD) in sera from patients with RA, systemic lupus erythematosus (SLE), and Crohn's disease, and from healthy controls. IgA binding to the crude mycobacterial antigens was significantly raised in RA sera, though IgG and IgM binding tended to be lower than in controls. Both IgA and IgG binding to the heat shock proteins were significantly raised in the RA sera. Smaller significant rises in both classes were seen in sera from patients with SLE, and in the IgA class only to the 65 kD protein in Crohn's disease. The rises in IgG and IgA antibodies to the 65 kD protein in RA were significantly higher than in the other diseases, however. It is interesting that this protein is the one responsible for adjuvant arthritis in the rat. |