Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 21068 | Alclofenac: a review of its pharmacological properties and therapeutic efficacy in rheumat | 1977 Oct | Alclofenac is a non-steroidal anti-inflammatory agent advocated for use in rheumatoid arthritis, degenerative joint disease and ankylosing spondylitis. Published data to date, suggest that alclofenac 3g daily is comparable in efficacy with aspirin 4.8g daily, phenylbutazone 300 to 600mg daily and indomethacin 150mg daily. In Welsh patients, gastro-intestinal side-effects have generally been less frequent and milder than with the standard comparison drugs, but in other populations differences in the overall incidence of these side-effects have been less marked. Results of a long-term trial, as evidenced by alterations in certain biochemical indications of disease activity, suggest that alclofenac may possibly reduce the severity of the disease itself, but further studies will be needed to confirm this. However, at present alclofenac should be considered along with the other drugs of its type in the initial treatment of the arthritic patient. Skin rash is the most frequent side-effect, which in a small proportion of affected patients may be associated with systemic effects. A cutaneous reaction appears to be more likely in patients with a history of previous allergy to penicillin and other drugs. | |
| 6335422 | Clinical profiles of patients with antibodies to nuclear ribonucleoprotein. | 1984 Dec | Currently there are no widely accepted criteria for the diagnosis of MCTD. In this work we attempted to define the clinical profile of a group of 68 patients with anti nRNP antibodies, detected by immunoprecipitation in 0.6% agarose. The diagnosis of each collagen vascular disease was established in every patient, who met with the strict diagnostic criteria either at clinical presentation or during the follow-up period. Twenty-eight patients had SLE, 9 had classical erosive RA, three had PSS and one had PM. The only distinctive features in the group of SLE with anti nRNP was an increased incidence of anti Sm antibodies (p less than 0.05). In the RA group there was a trend towards a high frequency of Raynaud's phenomenon and swollen hands. At clinical presentation twenty-seven patients did not fulfil enough criteria to be diagnosed of any of the well-defined collagen vascular disease. They presented an undifferentiated syndrome, characterized clinically by Raynaud's phenomenon (100%), swollen hands (88.9%) and joint symptoms (88.9%), with scarce tendency of developing severe systemic manifestations. The main laboratory abnormalities in this group were hypergammaglobulinemia, mildly increased ESR, abnormal levels of CIC, negative anti nDNA and anti Sm antibodies, and the virtual absence of hypocomplementemia. During a clinical course of 96 +/- 72.5 months only one patient evolved into another collagen disease (SLE). The clinical course in the remaining cases, was stable improving with low doses of prednisone and/or NSAID. We suggest considering this undifferentiated syndrome as a distinct entity, for which the already classical term of MCTD could be reserved. | |
| 7193106 | Methadone binding to orosomucoid (alpha 1-acid glycoprotein): determinant of free fraction | 1981 Feb | The distribution of basic drugs in blood differs qualitatively from that of acidic drugs. The binding of racemic, d-methadone, and l-methadone to human plasma and isolated protein fractions was studied by equilibrium dialysis at 37 degrees. In plasma samples from 29 healthy subjects free fraction of dl-methadone was (mean% +/- SD) 10.62 +/- 1.43. There were significant variations among subjects (p less than 0.001). The free fraction of the d-isomer was 9.24 +/- 1.61% and of the l-isomer, 12.44 +/- 1.53%. Plasma albumin concentration and degree of binding do not correlate, but in normal hypoalbuminemic subjects the free fraction of dl-methadone correlates negatively with the concentration of alpha 1-acid glycoprotein (alpha 1-AGP), an acute-phase reactant protein. Percentage dl-methadone bound to purified human serum albumin (HSA) (4.1 mg/dl) was 36.60% (mean +/- SD). Isolated alpha 1-AGP bound dl-methadone more avidly. As the alpha 1-AGP increased from 0.05 to 2.0 gm/l, free fraction fell from 92.40% to 8.80%. Addition of alpha 1-AGP (0.05 to 2.0 gm/l) to a physiologic concentration of purified HSA or to whole plasma progressively increased methadone binding. In eight monozygotic twin pairs, within-pair differences in binding of dl-methadone were less than in eight dizygotic twin pairs. Less than 20% of naloxone, codeine, morphine, heroin, pentazocine, and diphenoxylate bound to alpha 1-AGP. Elevations of alpha 1-AGP that occur in a variety of diseases may alter the kinetic and pharmacologic activity of methadone. | |
| 1078825 | Complement fixation by rheumatoid factor. | 1975 Mar | The capacity for fixation and activation of hemolytic complement by polyclonal IgM rheumatoid factors (RF) isolated from sera of patients with rheumatoid arthritis and monoclonal IgM-RF isolated from the cryoprecipitates of patients with IgM-IgG mixed cryoglobulinemia was examined. RF mixed with aggregated, reduced, and alkylated human IgG (Agg-R/A-IgG) in the fluid phase failed to significantly reduce the level of total hemolytic complement, CH50, or of individual complement components, C1, C2, C3, and C5. However, sheep erythrocytes (SRC) coated with Agg-R/A-IgG or with reduced and alkylated rabbit IgG anti-SRC antibody were hemolyzed by complement in the presence of polyclonal IgM-RF. Human and guinea pig complement worked equally well. The degree of hemolysis was in direct proportion to the hemagglutination titer of the RF against the same coated cells. Monoclonal IgM-RF, normal human IgM, and purified Waldenström macroglobulins without antiglobulin activity were all inert. Hemolysis of coated SRC by RF and complement was inhibited by prior treatment of the complement source with chelating agents, hydrazine, cobra venom factor, specific antisera to C1q, CR, C5, C6, or C8, or by heating at 56 degrees C for 30 min. Purified radiolabeled C4, C3, and C8 included in the complement source were bound to hemolysed SRC in direct proportion to the degree of hemolysis. These data indicate that polyclonal IgM-RF fix and activate complement via the classic pathway. The system described for assessing complement fixation by isolated RF is readily adaptable to use with whole human serum. | |
| 136815 | [Sulindac: Clinical test of a new antiinflammatory agent in rheumatoid arthritis (author's | 1976 | Sulindac, a new non steroidal antiinflammatory agent has been compared with acetylsalicylic-acid in a six week controlled double blind study in 28 patients with rheumatoid arthritis. In continuation of this study all patients have been treated with Sulindac up to 18 months. Sulindac has proved to be statistically significant superior to acetylsalicylic-acid as regarding the achieve of pain during the day, of morning stiffness, of gripping of the right hand and evaluation of patients response to the drug. Moreover markedly fewer adverse reactions especially of the gastrointestinal tract were seen. During the following long term study, when 19 patients were treated with Sulindac, a further statistically significant improvement of all controlled parameters up to the complete relief of complaints was observed. A reduction of the daily dose could be established. Laboratory evaluations as well as controlls of EKG and blood pressure showed no evidence of any organ toxicity of this drug. | |
| 6353568 | IgA antibodies to Klebsiella pneumoniae in ankylosing spondylitis. | 1983 | Serum IgA antibodies to Klebsiella pneumoniae were measured in 65 patients with ankylosing spondylitis (AS) during different phases of disease activity and compared with the antibody level in 21 psoriatic arthritis (PsA) patients, 43 rheumatoid arthritis (RA) patients and 57 healthy controls. The mean IgA antibody to Klebsiella in AS patients with an erythrocyte sedimentation rate (ESR) greater than or equal to 15 mm/h was significantly higher than the antibody level in patients with an ESR less than 15 mm/h (p less than 0.02) and tended to increase with rising ESR. There was a significant difference in anti-Klebsiella antibody levels between AS patients with an elevated ESR and antibody levels in PsA patients (p less than 0.001), RA patients (p less than 0.001) and healthy controls (p less than 0.005). There was no difference between healthy controls and patients with PsA, RA or AS patients with a low ESR. The IgA anti-Klebsiella antibody was specifically absorbed out from sera with inactivated klebsiella pneumoniae organisms. Antibody levels to Candida albicans and Escherichia coli did not differ in patients vis-Ã -vis control subjects. The mean serum anti-Klebsiella IgA level was found to be higher in patients who were either clinically active or had positive faeval cultures, when compared with patients with inactive disease and negative cultures, but these differences were not statistically significant, although when both parameters were examined together a significant additive effect was detected (p less than 0.001). It is concluded that patient with AS exhibit a specific elevation of serum IgA antibody to Klebsiella antigen. | |
| 4051593 | Lymphocytes from the site of disease but not blood lymphocytes indicate the cause of arthr | 1985 Oct | The [3H]thymidine uptake procedure for measuring lymphocyte responses was applied to lymphocytes derived concurrently from synovial effusions and from peripheral blood. The stimulating antigens were crude preparations of those micro-organisms that are related to the enteritis and the non-gonococcal urethritis that precipitate reactive arthritis. Salmonella, shigella, and campylobacter antigens stimulated synovial but not peripheral blood lymphocytes in eight cases of enteric reactive arthritis. Ureaplasma or chlamydia antigens, or both, stimulated synovial lymphocytes in all 12 cases of sexually transmitted reactive arthritis, whereas peripheral blood lymphocytes were only stimulated in four of the 12 cases. In 14 cases of rheumatoid arthritis reactions to either enteric or ureaplasma/chlamydia antigens were minimal from either synovial or peripheral blood lymphocytes. It is concluded that synovial rather than peripheral blood lymphocytes indicate the microbiological cause of reactive arthritis and that similar studies of lymphocytes from the site of local disease might be productive in other diseases. | |
| 7084277 | The phototoxic effects of benoxaprofen and their management and prevention. | 1982 | During clinical trials with benoxaprofen, some patients noted burning and stinging in the skin when exposed to light and some developed onycholysis. A four-part prospective study was undertaken. During the first part of the study it was demonstrated that (1) benoxaprofen is associated with a hypersensitivity to long wave-length ultraviolet light (UVA). During the remaining three parts of the study, patients were exposed to very high doses of UVA light in order to try to induce a photosensitivity response. These studies demonstrated that (2) the symptoms of burning and stinging in the skin and signs of erythema and induration after very high-dose UVA exposure (30 Joule) may be prevented by the prophylactic application of a factor 15 sunscreen; (3) exposure to sunlight is required for the development of onycholysis in patients on benoxaprofen; and (4) the development of onycholysis was prevented by the regular use of a nail polish containing sunscreen. A commercially available, colored, opaque nail polish also would be expected to provide protection from onycholysis. | |
| 16038 | Hydrolysis of the elastase substrate succinyltrialanine nitroanilide by a metal-dependent | 1977 May | A new type of enzyme hydrolyzing the elastase substrate succinyl-L-alanyl-L-alanine-4-nitroanilide has been found in cell-free rheuma todi synovial fluid. Normal plasma and osteoarthritic synovial fluid contained relatively little enzyme. The pH optimum was 8.0. Unexpectedly, the enzyme activity was not due to leukocyte elastase or any proteinase bound to alpha2-macroglobulin. The enzyme activity was metal-dependent being inhibited by chelating agents but not by di-isopropylfluorophos phate or thiol-blocking reagents. Gel chromatography showed the enzyme activity was associated with material of high molecular weight. On Sepharose 4B chromatography two-thirds of the activity eluted in the void volume and one-third in a position of about 106 mol wt. Utracentrifugation showed that both components were associated with lipid. The buoyant density of the higher molecular weight material was 1.15-1.22 g/ml., and that of lower molecular weight material was 1.2-1.33 g/ml. No latency of the enzyme was revealed by freezing and thawing or treatment with detergents. The nature of the enzyme is discussed. It is likely to be a proteinase possibly bound to some kind of membrane fragment. | |
| 7136583 | Gait analysis with an angle diagram technique: application in healthy persons and in studi | 1982 Oct | Normal step dimension data were obtained from six healthy subjects by recording step length and step frequency at different walking speeds. In addition, an externally applied goniometer system was used to measure the sagittal knee and hip joint movements in eleven persons with healthy joints. The movements were recorded on an oscilloscope in the form of a so-called angle diagram during walking. In seven patients undergoing Marmor knee arthroplasty the same gait analysis as in the healthy subjects was performed before and after operation. The results were compared by a clinical scoring system for pain and walking ability and by measurement of passive knee mobility and passive extension deficit. The angle diagram permitted recording of functional sagittal mobility and functional extension deficit during walking. The functional knee mobility during walking was found to be pain-dependent; thus increasing pain is accompanied by a gradual decrease in functional mobility despite good passive knee joint motion. In several patients the functional extension deficit during walking was increased compared with the extension deficit on passive movement. The clinical improvements after knee arthroplasty corresponded very well to the increased functional knee mobility during walking measured on the angle diagram. | |
| 334608 | Butacote and ibuprofen: a comparative assessment in rheumatic diseases in general practice | 1977 | A multicentre double-blind trial in general practice compared Butacote (enteric-coated phenylbutazone) 300 mg daily, ibuprofen 1200 mg daily, and a placebo in the treatment of rheumatic conditions. Each patient recieved two of the three treatments for one month each. Twenty-nine doctors admitted 193 patients. One hundred and sixty-eight patients (sixty-four with inflammatory polyarthritis, and sixty-three with osteoarthrosis) completed the study, which showed that Butacote was significantly better than both ibuprofen and placebo for the relief of pain and morning stiffness, and improvement of function. Butacote was significantly preferred to both ibuprofen and placebo by patients and doctors, to placebo by the patients. Ibuprofen was significantly better than placebo for relief of morning stiffness and for reducing the amount of supplementary analgesics. All three preparations were well tolerated and showed a similar incidence of gastric side-effects. It is concluded from this study that Butacote is more effective and as well tolerated as ibuprofen in the treatment of rheumatic conditions in general practice. | |
| 6404473 | Correlation of persistently high serum amyloid A protein and C-reactive protein concentrat | 1983 Apr 30 | The importance of serum amyloid A protein in the progression of renal failure was studied over three years in 28 patients with secondary (amyloid A type) amyloidosis predominantly due to rheumatoid arthritis. Creatinine clearance, the amount of protein in the urine, and serum amyloid A and C-reactive protein concentrations were determined regularly. Linear regression analysis showed a close correlation between the change in creatinine clearance each year and both serum amyloid A concentrations (20 patients: r= -0.83, p less than 0.001) and C-reactive protein concentrations (28 patients: r= -0.80, p less than 0.001). The correlation between serum amyloid A and C-reactive protein concentrations was also significant (317 parallel measurements: r=0.81, p less than 0.001). These findings suggest that monitoring serum amyloid A or C-reactive protein concentrations is valuable in assessing the prognosis in secondary amyloidosis and that therapeutic measures that lower serum amyloid A concentrations may reduce the formation of amyloid. | |
| 4586839 | Reactivity of RA and SLE lymphocytes stimulated by anti-Ig antibodies. | 1973 Oct | In vitro human lymphocyte stimulation response was studied using phytohaemagglutinin and immunoabsorbent-column purified rabbit antibodies to γA, γM and γG with peripheral blood lymphocytes from normal subjects as well as patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, lymphocytes from a group of patients receiving immunosuppressive therapy in connection with renal transplantation or metastatic carcinoma were studied as controls. No essential differences in degree of response were noted when normal subjects were compared to RA patients, however, most SLE patients showed a decreased response with the various purified anti-Ig antibodies. This hyporesponsiveness was most marked using anti-IgM and anti-IgG antibody (P<0·01). Patients receiving immunosuppressive drugs for maintenance of renal transplants or in the course of treatment for metastatic carcinoma also showed significant depression of responses in lymphocyte culture (P<0·01) after stimulation with anti-IgG, IgA, or IgM antibody. In addition, baseline unstimulated cellular incorporation of labelled thymidine, as well as degree of stimulation with phytohaemagglutinin, was significantly reduced (P<0·01) among the immunosuppressed control group when compared to normals or the groups of SLE or RA patients. Diminished culture response in SLE patients and subjects receiving immunosuppressive therapy may be related to concurrent therapy or to other alterations intrinsic to the disease process itself. | |
| 6210236 | [A new HLA-B antigen: HLA-Bw 59]. | 1984 Sep | The HLA-B8 antigen is one of the well-defined and characteristic antigens associated with organ specific autoimmune diseases in Caucasians. In the Japanese, HLA-B8 positives have been assumed to be extremely rare. By using some HLA-B8 typing sera, a new HLA-B antigen, HLA-Bw4 positive, was found in the Japanese. This new HLA-B antigen, tentatively named HOK-1, showed a phenotype frequency of 3.7% and a gene frequency of 1.9 +/- 0.6%. The strong linkage disequilibrium was noted between HOK-1 and HLA-Cw1 genes. HOK-1 antigenic specificity was assigned as HLA-Bw 59 by the WHO nomenclature committee after the 8th International Histocompatibility Workshop. There were no significant associations of this antigen with following diseases: rheumatoid arthritis, psoriasis vulgaris, myasthenia gravis, Behcet's disease and asthma, so far as, in the Japanese, compared with that the HLA-B8 antigen has a characteristic association with organ specific autoimmune diseases in Caucasian. | |
| 152571 | [Study of C3 and C4 complement components of synovial fluids in connective tissue diseases | 1978 | C3 and C4 levels and the relative concentration of C3 degradation products were measured in fifty pairs of synovial fluids and sera of patients who suffered from different connective tissue diseases. Inverse correlation between C4 level and C3 breakdown products were found in synovial fluids of different groups. Compared to the other groups of patients, the highest increase of C3 degradation was found in RA. patients and it occurred in the SF all of these patients. In arthrosis cases we failed to find any degradation of C3. Of the seven investigated ankylosing spondylitis only two showed some degree of activation of C3 in the SF. Our results suggest that the occurrence and degree of degradation of C3 complement component is a valuable laboratory parameter in the study of connective tissue diseases. | |
| 6279161 | Identification of plasma kallikrein as an activator of latent collagenase in rheumatoid sy | 1982 Mar 18 | Rheumatoid synovial fluid contains an activator of latent collagenase from culture medium of pig synovium. The activator was purified by gel chromatography on Ultrogel AcA 44 and affinity chromatography on soybean trypsin inhibitor coupled to Sepharose 4B. The purified material was homogeneous on SDS-polyacrylamide gel electrophoresis with Mr 88 000. The activator had limited proteolytic activity against azo-casein, but showed amidase activity on Pro-Phe-Arg-NMec, Z-Phe-Arg-NMec, D-Val-Leu-Arg-NPhNO2 and D-Pro-Phe-Arg-NPhNO2, with an optimum at pH 8.0. Activity was completely inhibited by diisopropyl fluorophosphate, soybean trypsin inhibitor, leupeptin and Pro-Phe-Arg-CH2Cl, whereas lima bean trypsin inhibitor, Tos-Lys-CH2Cl, a specific inhibitor of factor XIIa from maize, EDTA and iodoacetate were not inhibitory. These properties of the activator suggested that it might be plasma kallikrein (EC 3.4.21.34), and the possibility was further examined. The activator was treated with [3H]diisopropyl fluorophosphate, and run in SDS-polyacrylamide gel electrophoresis with reduction; a radioautograph of the gel showed a pair of [3H]diisopropyl phosphoryl-labelled bands (Mr 36 000 and 34 000) identical to those obtained with authentic plasma kallikrein. Double immunodiffusion with monospecific antiserum against human plasma kallikrein confirmed the identification. This is the first demonstration of collagenase-activating activity of plasma kallikrein, and raises the possibility that activation of prokallikrein in the inflamed joint space may contribute to the disease process not only by the production of bradykinin, but also by activating latent collagenase. | |
| 6994990 | Renal injury in patients with rheumatoid arthritis treated with gold. | 1980 Aug | While severe nephrotoxicity is uncommon during gold therapy of rheumatoid arthritis (RA), the prevalence of mild nephrotoxicity has not been investigated. To study this, levels of leucine aminopeptidase (LAP) and N-acetyl-beta-glucosaminidase (NAG) (nmole/hr/mg urinary creatinine), and beta 2-microglobulin (beta 2M) (microgram/mg urinary creatinine) were measured in urine samples from 33 patients with RA receiving gold and 28 patients with various musculoskeletal diseases not receiving gold. Each patient had a normal urinalysis and blood urea nitrogen or serum creatinine. LAP was above 30 in 55% of RA patients and 7% of controls (p < 0.01). NAG was above 100 in 70% of RA patients and 14% of controls (p < 0.01). In 8 RA patients, NAG was over 200; LAP was over 100 in 4, but in none of the controls. Beta 2M was above 0.32 in 7 of 23 female RA patients and in none of 12 female controls (p = 0.012) and none of the male patients. Patients who excreted high levels of beta 2M also excreted high levels of NAG and LAP. These data show that gold in therapeutic doses affects renal tubular cells, cauing the release of NAG and LAP from lysosomes and brush borders of the cells. This may represent the mildest stage of nephrotoxicity. Elevated beta 2M in the urine of some patients indicate a degree of nephrotoxicity sufficient to cause renal tubular dysfunction. | |
| 902454 | Patterns of plasma concentrations and urinary excretion of salicylate in rheumatoid arthri | 1977 Oct | Intersubject differences in the volume of distribution, whole body clearance, and steady-state plasma concentrations of salicylic acid (SA) were studied in a series of patients with rheumatoid arthritis and healthy control subjects. The measurement of the plasma concentration of SA 12 hr after an oral dose of 1.2 gm aspirin appears predictive of the success of long-term dosage of aspirin. Concentrations below 5 microgram/ml in this single-dose test were associated with failure to achieve therapeutic plasma concentrations of SA (above 150 microgram/ml during long-term therapy with approximately 4.8 gm aspirin per day. Conversely, plasma concentrations above 10 microgram/ml in the single-dose test were associated with levels above 150 microgram/ml during long-term therapy. The volume of distribution of SA correlated poorly with body weight (r = 0.51, p less than 0.01) and did not correlate significantly with plasma albumin levels. Corticosteroids appear to induce the metabolism of SA and most subjects dosed with oral corticosteroids and aspirin 4.8 gm/day did not attain plasma levels of SA above 150 microgram/ml. The clearance of SA was greater in male than in female patients. The difference appears to be of clinical significance since fewer men than women achieved therapeutic plasma concentrations of SA. | |
| 3831362 | Methotrexate and the liver. | 1985 Dec | The findings of liver studies in 29 patients who were treated with low dose pulse methotrexate for rheumatoid arthritis (RA) are described. The biopsy specimens of 22 patients (76%) showed liver abnormalities, but cirrhosis did not develop in any patient. There were no statistically significant differences in age, duration of treatment, or cumulative dose between patients in whom abnormal liver histology developed and those in whom it did not. Our findings showed that isolated elevations of the aminotransferase enzymes or alkaline phosphatase levels did not predict liver disease, nor did the absence of elevation of these enzymes assure the absence of liver disease. Serial elevations of the aminotransferase and/or alkaline phosphatase enzyme levels and the development of hypoalbuminemia during treatment were specific indicators of the development of liver disease. In the patients studied, significant liver disease did not develop before 2 years of therapy or with a cumulative dose of methotrexate of less than 1500 mg. | |
| 1082832 | [Anti-inflammatory, analgesic and antipyretic actions of 1-(m-chlorophenyl)-3-N, N-dimethy | 1975 Nov | We have reported that PZ-177 was found to have potent inhibitory activity on acute inflammatory edema. In this paper, the anti-inflammatory, analgesic and antipyretic properties of PZ-177 were assessed by a battery of standard tests. PZ-177 inhibited the increased vascular permeability induced by histamine, xylene and acetic acid. The activity was the same as the anti-edematous one and was more potent than that of mepirizole. PZ-177 did not inhibit ultraviolet erythema in guinea pigs, proliferation of granulation tissue in cotton pellet and granuloma pouch tests of rats and adjuvant arthritis in rats. Wound healing was not prolonged and the agent was weak in ulcerogenic action. PZ-177 did not affect heat denaturation of bovine serum albumin at pH 5.3, but inhibited hyperthermic hemolysis at pH 7.4 and exerted a stabilizing effect on biological membranes. This is considered to be one of the mechanisms of action. When analgesic action was tested by the writhing and Haffner's methods in mice, the compound revealed a more potent activity than did mepirizole and aminopyrine. Utilizing the Randall-Selitto's analgesic method in rats, a significant rise in pain threshold was obtained only at the inflamed foot. The antipyretic action was less than aminopyrine in febrile rabbits. From the above results, PZ-177 may be classified as a potent analgesic and anti-inflammatory agent but has no effect on proliferation of granulation tissue and chronic inflammatory disease. |