Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8922561 | Nonsteroidal anti-inflammatory drugs and acute renal failure in the elderly. A risk-benefi | 1996 Nov | Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most valuable groups of available medications because of their effectiveness in relieving pain, particularly that associated with rheumatoid arthritis. They are also among the most commonly prescribed drugs and, because of their availability over-the-counter, they are among the most widely consumed agents, especially by elderly people. Older individuals are more predisposed to the renal adverse effects of NSAIDs, because of: (i) age-associated changes in renal function; (ii) the prevalence of comorbid conditions (congestive heart failure, hypertension, hepatic cirrhosis, renal insufficiency); and (iii) the pervasive use of concomitant drugs that affect kidney function (diuretics, antihypertensives). However, because the incidence of NSAID-induced acute renal failure (ARF) is relatively low, and because it occurs in an identifiable and therefore preventable setting, the benefits of limited NSAID use outweigh the risks of this adverse effect. Using NSAIDs for a restricted period of time at the lowest effective dosage, and informing patients of the conditions in which ARF can occur, should minimise the risk of this effect. If the use of an NSAID in a patient at potential risk of ARF is necessary, close monitoring of renal function should further reduce the already low risk:benefit ratio for this adverse effect. | |
| 8856158 | Translocation of the neutrophil kinin moiety and changes in the regulation of kinin recept | 1996 Jun | A molecular response to cell injury is the formation of chemotactic mediators that attract neutrophils to sites of inflammation. The question whether neutrophils contribute to circulating levels of kinins was examined in infections and inflammatory disorders. This novel hypothesis was tested using circulating neutrophils harvested from patients with tuberculosis meningitis and pneumonia. These neutrophils showed a distinct loss of only the kinin moiety from the kininogen located on the external surface. A similar loss of the kinin peptide was observed on the synovial fluid neutrophils obtained from the swollen, inflamed joints of patients with rheumatoid arthritis. The intriguing question is whether the circulating neutrophils simply reflect those cells re-entering the circulation from sites of inflammation. Anti-peptide antibodies to the peptide loops of cloned B1 and B2 receptors have provided a powerful probe for the cellular identification of the two kinin receptor families. We report the first localisation of B1 receptors on the basement membranes of bronchopulmonary cells and the surrounding fibrous stroma in transbronchial biopsies taken from patients with interstitial lung disease associated with progressive systemic sclerosis. Although binding of labelled bradykinin to neuronal membranes has been demonstrated, this is the first conclusive evidence for the presence of B1 kinin receptors in the neurons of human hypothalamus, caudate nucleus and the substancia gelatinosa of the spinal cord. Mapping of the B2 receptors in human tissues shows upregulation on the neutrophils gathered from inflamed joints, and absence from cell membranes of acutely rejecting transplant kidney. In addition, B2 receptors have also been demonstrated in neurons of the brain hypothalamus, caudate nucleus and cerebral cortex. Kinin receptor localisations in human tissue has considerable therapeutic implications. | |
| 8811168 | Serum hyaluronan as a disease marker. | 1996 Jun | Hyaluronan is a connective tissue polysaccharide which has also been found in blood serum in concentrations < 100 micrograms/L (average 30-40 micrograms/L in middle-aged persons). The serum level is regulated by the influx of the polysaccharide from the tissues via lymph and its receptor-mediated clearance by liver endothelial cells. Markedly high serum levels are noted in certain liver diseases, especially in patients with cirrhosis, when the clearance is impaired. In these cases serum hyaluronan can be used to follow the development of the disease. Serum hyaluronan is also a sensitive marker for impending rejection of liver transplants. Patients with rheumatoid arthritis constitute another major group with increased serum hyaluronan, but in this case the level varies markedly during the day corresponding to physical activity. There are good indications that in these subjects the excess hyaluronan comes from the joints. Under stringent sampling conditions of serum it should be possible to extract interesting information on the inflammatory joint process. Increased hyaluronan levels are also seen in other inflammatory diseases and it is of special interest that high hyaluronan levels in patients with septic conditions is a sign of poor prognosis. Certain tumours, notably Wilms' tumour and mesothelioma, produce factors which activate synthesis of hyaluronan and increase its serum level. Rare hereditary diseases with disturbances of hyaluronan metabolism and elevated blood levels have also been discovered, e.g. Werner's syndrome and cutaneous hyaluronanosis. Information accumulated during the last decade regarding the metabolism of hyaluronan has made this polysaccharide an interesting clinical marker for a number of pathological conditions. | |
| 8737745 | Gold salts inhibit osteoclastic bone resorption in vitro. | 1996 May | Loss of bone mass is commonly associated with rheumatoid arthritis (RA) and is increasingly considered to be due to the increased activity of bone-resorbing osteoclasts. Gold salts such as auranofin (AF), aurothioglucose (ATG) and aurothiomalate (ATM) have beneficial therapeutic effects in RA, but their mechanisms(s) of action is not well understood. In the present study we have examined the effects of these 3 gold salts on osteoclastic bone resorption in vitro, using the bone slice assay where bovine cortical bone slices are resorbed by osteoclasts disaggregated from the long bones of neonatal rats. All 3 gold salts inhibited osteoclastic bone resorption with IC50 values of AF = 0.1 microgram/ml, ATG and ATM = 1 microgram/ml. All 3 compounds caused a decreased survival of osteoclasts on bone slices at high concentrations indicating a cytotoxic effect that was also observed in a cytotoxicity assay with osteoblast-like UMR-106 cells. Preincubation of bone slices with various concentrations of AF followed by extensive washing prior to use in the bone slice assay also resulted in an inhibition of bone resorption (IC50 = 4 micrograms/ml) and osteoclast survival on the bone slices preincubated with high concentrations of AF was decreased. Since these effects were obtained with therapeutic concentrations of gold salts, these results indicate that inhibition of osteoclastic bone resorption by gold salts may, at least in part, account for their beneficial effects in RA. | |
| 8602122 | Methotrexate and misoprostol for abortion. | 1996 Apr 26 | ||
| 8565320 | IL-6-induced anaemia in rats: possible pathogenetic implications for anemia observed in ch | 1996 Feb | Anaemia of chronic disease (ACD) is frequently found in rheumatoid arthritis (RA). In the pathogenesis of ACD both cytokines, such as tumour necrosis factor-alpha (TNF-alpha), IL-1 and IL-6 as well as a relative deficiency of erythropoietin (EPO), are thought to play a key role. In the present study the role of IL-6 in the pathogenesis of this anaemia was investigated. IL-6 was administered intraperitoneally to rats for 14 sequential days. It appeared that IL-6 was able to induce anaemia. No evidence for suppression of bone marrow erythropoiesis or enhanced sequestration of erythrocytes in the liver was found. However, decreased plasma and bone marrow iron contents were observed in anaemic rats. Blood loss in intestinal tissue was demonstrated using erythrocyte labelling with 99mtechnetium. Histologically this was associated with inflammatory cell infiltration, oedema and bleeding in the intestinal wall. In conclusion, IL-6 induced anaemia in rats. This anaemia was caused by intestinal blood loss. | |
| 9112233 | Primary biliary cirrhosis sera recognize not only gp210 but also proteins of the p62 compl | 1996 | We have recently observed reactivity of primary biliary cirrhosis (PBC) sera with several proteins bearing N-acetylglucosamine residues from rat liver nuclear envelopes. The aim of this study was to characterize the reactive antigens. Sera from 31 patients with PBC, 30 with rheumatoid arthritis (RA) and 30 with Sjögren's syndrome (SS) were examined. Rim-like immunofluorescence staining was observed in 15 of 31 (48%) sera from patients with PBC, in 1 of 30 with RA and in 1 of 30 with SS. Upon immunoblotting using preparations of whole rat liver nuclear envelopes and their Triton X 100-KCl extract as antigen sources, a 200 kDa protein band was observed in 9 of sera with PBC. Furthermore, upon immunoblotting using the wheat germ aggulutinin-bound fraction of rat liver envelope as antigen, 62, 60 and 54 kDa protein bands corresponding to components of the p62 complex in the nuclear pore complex (Kita et al. Biochem. 113, 377-382) were observed in 7, 5 and 6 samples respectively, of the 31 PBC sera. Our data suggest that PBC sera recognize not only the 210 kDa protein but also the p62 complex proteins. | |
| 8565575 | Novel anti-silicone surface-associated antigen antibodies (anti-SSAA(x)) may help differen | 1996 | The frequency of novel autoreactive antibodies to silicone surface associated antigens (anti-SSAA(x)) was measured in healthy control patients, symptomatic patients with breast implants, asymptomatic patients with breast implants, and control patients with classical rheumatological diseases. The frequencies of elevated anti-SSAA(x) antibodies in 310 symptomatic breast implant patients were 17.4% anti-SSAA(fn), 12.9% anti-SSAA(col1), and 7.4% anti-SSAA(col3) and 7.1% anti-SSAA(fbgn) [Normal (n = 173) = 0.6% for all four tests] (p < .005). In 11 asymptomatic breast implant patients, the frequencies of elevated values for the same anti-SSAA's were 0%, 9%, 0%, and 0% respectively, while in 50 patients with rheumatoid arthritis, the frequencies were 4%, 0%, 6% and 2% respectively. The anti-SSAA(x) profile for symptomatic patients with breast implants was different than the profile for control healthy patients (p < .005 on all eight tests) but differed significantly by two measures, anti-SSAA(fbgn) and anti-SSAA(col3), from the profile for the 19 patients with systemic lupus erythematosus. We conclude that anti-SSAA(x) antibodies levels in symptomatic patients with breast implants are elevated, that the antibodies are associated with symptoms, and that they differ both qualitatively and quantitatively from healthy controls, asymptomatic patients with breast implants, and symptomatic patients with classical rheumatological diseases. | |
| 8706168 | [Effect of deoxynupharidine on immune function in vitro]. | 1995 Oct | Deoxynupharidine (DON) is an alkaloid isolated from rhizome Nuphar pumilum which has been extensively used in the treatment of rheumatoid arthritis and back and leg pains as a folk remedy in China. Data presented in this paper indicate that the DON has potent immunosuppressive activities. Mitogens or allogen induced lymphoproliferative responses of murine splenocytes or human tonsillar mononuclear cells (hTMNC) were markedly reduced when DON was added in the cultures. The trypan blue exclusion test showed that this inhibition was not exerted through a toxic effect. IL-2 activity in the supernatants was evaluated for its ability to support IL-2 independant cell line (CTLL-2) proliferation and the results showed that DON had no marked effect on IL-2 level, but inhibited the capacity of murine peritoneal macrophages to produce IL-1 and TNF, which play very important roles in the process of inflammation and immune response. This immunosuppressive actions of DON may partly account for some of its potential in the treatment of chronic inflammatory diseases, where immunological mechanisms are known to play a major pathogenic role. | |
| 7673283 | Humeral fractures after shoulder arthroplasty. | 1995 Sep | Nine humeral fractures occurred subsequent to 499 shoulder arthroplasties that had been performed between December 1978 and November 1987 at the Mayo Clinic. The time from the arthroplasty to the fracture averaged thirty-nine months (range, eight to 101 months). Seven patients were women and two were men, and the average age was seventy years (range, forty-five to eighty-five years). The arthroplasties were performed for rheumatoid arthritis in five patients and for the sequelae of trauma in four. Six patients had advanced osteopenia, and two had had an ipsilateral total elbow arthroplasty. Six of the fractures were centered at the tip of the prosthesis; one fracture (type A) extended proximally, and five (type B) did not. The three remaining fractures (type C) involved the humeral shaft distal to the implant and extended into the distal humeral metaphysis. Four fractures healed with non-operative treatment. Two fractures that had unacceptable alignment were treated successfully with operative intervention. Three fractures that were treated with immobilization in a splint failed to heal; two of those fractures eventually united after a revision of the prosthesis and bone-grafting was performed, and one fracture remained ununited. Radial nerve palsy developed postoperatively in two patients, and it resolved within three months. Five patients had poor active motion before the fracture, and two of them had even less motion after the fracture was treated. Our experience suggests that long oblique and spiral fractures can be successfully treated non-operatively, provided that the skeletal alignment is acceptable.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 7590879 | sLex is not responsible for the interaction of sLex-positive memory T lymphocytes with E-s | 1995 Sep | E-selectin in an adhesion molecule that is transiently and exclusively expressed on endothelial cells in response to inflammatory cytokines. In addition, E-selectin participates in the initial interaction of leucocytes with activated endothelial cells. This role of E-selectin in cell adhesion has made it a potential target for modulation of inflammatory processes that, for example, are occurring in autoimmune diseases such as rheumatoid arthritis. Although on granulocytes the ligand for E-selectin has been identified as the tetrasaccharide sialyl Lewis x (sLex), the molecular nature of this ligand on T lymphocytes has not yet been identified. In the present study, it was shown by fluorescence-activated cell sorter (FACS) analysis with the anti-sLex antibody CSLEX1 that T lymphocytes stimulated with phytohaemagglutanin (PHA), interleukin-2 (IL-2) and transforming growth factor-beta 1 (TGF-beta 1) expressed sLex. Furthermore, in a cell adhesion assay these activated T cells of the memory phenotype bound specifically to E-selectin-transfected Chinese hamster ovary (E-CHO) cells. This adhesion could be blocked with an anti-E-selectin antibody but not with CSLEX1. In the same assay, the interaction of sLex-positive U937 cells with the E-CHO cells could be inhibited both with anti-E-selectin and CSLEX1 antibodies. From these results it can be inferred that sLex on activated T lymphocytes is not responsible for the interaction with E-selectin. Rather, these results suggest that stimulated T lymphocytes express an additional E-selectin ligand(s) with much higher avidity for E-selectin than sLex. | |
| 7590949 | Antioxidant and anti-inflammatory property of Sandhika: a compound herbal drug. | 1995 Jun | The present study was envisaged to assess the rationality for the use of "Sandhika", a popular Ayurvedic drug in rheumatoid arthritis. This drug, when tested against carrageenan induced paw oedema and cotton pellet granuloma, showed significant anti-inflammatory activity at the dose of 0.25 g/kg body weight. The antioxidant property was assessed by determining cumene hydroperoxide (CHP) induced lipid peroxidation and reduced glutathione content in rat liver homogenate (in vitro). Experiments show the significant protection against lipid peroxidation at the dose of 80 micrograms/ml, measured as reduction in the level of malondialdehyde (MDA) induced by 1.5 mM cumene hydroperoxide (CHP). This effect was accompanied by the maintained reduced glutathione (GSH) content in drug treated rats. Oral treatment of drug up to 2 g/kg body weight for 15 days did not show any rise in serum transaminases (SGOT and SGPT). The results suggest that "Sandhika" which is an indigenous drug for inflammation with no detectable adverse effect, might be acting through scavenging the free radicals. | |
| 7897551 | Report: the pill's health benefits appear to far outweigh its risks. | 1995 Jan | ||
| 7979843 | Costochondritis. A prospective analysis in an emergency department setting. | 1994 Nov 14 | BACKGROUND: Costochondritis (CC) is a common, but poorly understood condition among patients with chest wall pain. We have prospectively analyzed distinctive features of patients presenting to the emergency department with chest pain and CC. METHODS: Patients with a chief complaint of chest pain, not due to trauma, fever, or malignancy, were prospectively evaluated for the presence of CC and compared with another chest pain group without CC. RESULTS: Of 122 consecutive patients studied, 36 had CC (30%) and in 17 the pain induced reproduced the original one (15%). Women made up 69% of the patients with CC (vs 31% of control subjects) and Hispanics 47% (vs 24% of control subjects). Only three patients (8%) with CC met the American College of Rheumatology criteria for fibromyalgia, while none of the control subjects did. Widespread pain was more common in the CC group (42% vs 5%). The mean sedimentation rate in the CC group was 44 +/- 31 mm/h vs 41 +/- 31 mm/h in the control group. The acute myocardial infarction rate was 6% in the CC group vs 28% in the control group. Rheumatoid arthritis and osteoarthritis were diagnosed in three and two patients, respectively, of 32 patients with CC cases. One year later, 11 (55%) of 21 patients with CC were still suffering from chest pain, but only one third still had definite CC. CONCLUSIONS: Costochondritis is common among patients with chest pain in an emergency department setting, with a higher frequency among women and Hispanics. It is associated with fibromyalgia in only a minority of cases. Patients with CC appear to have a lower frequency of acute myocardial infarction. Spontaneous resolution is seen in most cases at 1 year. | |
| 7978805 | A high throughput fluorogenic substrate for stromelysin (MMP-3). | 1994 Sep 6 | Stromelysin, a member of the matrix metalloproteinase family of enzymes, has been implicated in the pathogenesis of tumor metastasis and inflammatory diseases such as rheumatoid arthritis. To screen prospective inhibitors of this protease, we developed a fluorogenic substrate with excitation and emission spectra compatible with commercially available 96-well plate readers. The substrate is based on the addition of 6-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino] hexanoic acid (NBD) (EX467/EM534) and 7-dimethylaminocoumarin-4-acetate (DMC) (EX368/EM459) to the previously reported peptide substrate for stromelysin, Arg-Pro-Lys-Pro-Leu-Ala-Nva-Trp-NH2. The new substrate, NBD-Arg-Pro-Lys-Pro-Leu-Ala-Nva-Trp-Lys-(DMC)-NH2 is 95% quenched and the fluorescent product, Nva-Trp-Lys(DMC)-NH2 is easily detected (EX350/EM465). In competition assays the new fluorogenic substrate has a relative kcat/Km that is one half that of the parent peptide. The fluorophores NBD and DMC were chosen based on the high fluorescence yield of DMC and the overlap of the emission spectrum of DMC and excitation spectrum of NBD which results in an efficient energy transfer system in the intact substrate. These characteristics make this an excellent substrate for routine determination of in vitro activities of stromelysin inhibitors. | |
| 7833866 | [Osteoarthritis with rice bodies rich in calcium microcrystals. 4 cases with ultrastructur | 1994 Jun | Rice bodies are often found in inflammatory joint fluid specimens, especially from rheumatoid arthritis patients, but have rarely been reported in osteoarthritis. We found rice bodies in knee joint fluid specimens from four of 88 patients with osteoarthritis. There were three males and one female. Age ranged from 61 to 86 years. Three patients had slowly progressive knee osteoarthritis and one had rapidly destructive disease. Abundant, recurrent effusions occurred in all four patients despite one to five local corticosteroid injections per patient and radiation synovectomy in two patients. The joint fluid specimens contained 120 to 320 cells/mm3 and large numbers of rice bodies that stained with alizarin red S. Transmission electron microscopy studies showed that the rice bodies were composed of fibrin and contained numerous intra- and extra-cellular calcium crystals composed of apatite alone in two cases and of a combination of apatite and calcium pyrophosphate dihydrate in the two others. Collagen fibers and fragments of bone and cartilage were present in a few rice bodies. Phagocytic cells, type C synoviocytes, chondrocytes and a few inflammatory cells were also seen. These rice bodies composed mainly of fibrin and apatite may have played a role in the pathogenesis of the recurrent joint effusions in our patients. | |
| 8072374 | Composition of peritoneal macrophage membranes in autoimmune MRL lpr/lpr mice. | 1994 | Adult MRL lpr/lpr mice display phenotypic features that are consistent with both rheumatoid arthritis and systemic lupus erythematosus. Previous studies have reported that peritoneal macrophages harvested from this model have an increased propensity for both spontaneous and elicited release of prostaglandins and leukotrienes relative to immunologically normal control mice. To investigate whether one aspect of the differences in secretory potential between autoimmune and normal mice was at the level of increased substrate availability, gas chromatographic analysis of peritoneal macrophage membranes from autoimmune MRL lpr/lpr, young lpr, wild type +/+, and immunologically normal mice was done. The results demonstrate enrichment of arachidonate in adult lpr macrophage membranes in all major phospholipid classes relative to young lpr, +/+ and immunologically normal C3H/HeN mice. Similarly, there was an increased mole % of arachidonic acid in lpr mice relative to controls. Elevated membrane arachidonate may contribute to the increased propensity of autoimmune strains to participate in the inflammatory process. | |
| 7816786 | Tolfenamic acid: clinical experience in rheumatic diseases. | 1994 | Tolfenamic acid (TA) is an interesting drug for the treatment of rheumatic diseases because of its capacity to inhibit the synthesis of leukotrienes. It may have fewer upper gastrointestinal side effects than other NSAIDs which inhibit only the synthesis of prostaglandins. Several controlled and non-controlled studies on the clinical efficacy and side effects of TA have been carried out since the early seventies. These studies include about 900 patients suffering from different rheumatic diseases. The clinical efficacy of TA has proved to be at least as good as that of control drugs in all double-blind trials. We have compared the analgesic effect of ten NSAIDs in patients with rheumatoid arthritis, using a single-blind method by asking the patients which one of two drugs was the better. The study gave a rank order to the drugs favoured by the patients and the results showed that TA was among the four best drugs together with naproxen, indomethacin, and diclofenac. The side effect profile of TA is different from that of other NSAIDs. The number of upper gastrointestinal side effects during TA treatment was less than half the number during treatment with control NSAIDs in eight double-blind studies. On the other hand, dysuria was found only during TA treatment. In 1989 the official side effect registers of Denmark and Finland included a total of 462 side effect reports. The frequency of side effects per treatment day was about the same as for other NSAIDs according to these reports.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 7544775 | Vascular permeability factor, tumor angiogenesis and stroma generation. | 1994 | Vascular permeability factor (VPF/VEGF) is a highly conserved multifunctional cytokine that acts directly on endothelial cells (ECs) to activate phospholipase C and induce [CA2+]i transients. Two high-affinity receptors, both tyrosine kinases, have been described. VPF/VEGF has at least two important roles in tumor biology: (1) it potently increases microvascular permeability to plasma proteins, thereby modifying the tumor extracellular matrix to promote the ingrowth of fibroblasts and new blood vessels, and (2) it is a selective EC mitogen. VPF/VEGF is also involved in several other nonmalignant processes with a pathogenesis analogous to that of tumor stroma generation, including wound healing and rheumatoid arthritis. | |
| 8253043 | [Successful lysis therapy in acute unilateral renal vein thrombosis]. | 1993 Dec 10 | A nephrotic syndrome developed in a 50-year-old man who, because of rheumatoid arthritis for the last three years, had been receiving gold therapy (30-50 mg sodium aurothiomalate weekly for 10 months). Treatment for the nephrotic syndrome was initiated with 100 mg prednisone daily. Ten days later he complained of severe pain in his right flank and haematuria was noted. Serum creatinine concentration increased from 1.0 to 1.8 mg/dl, while creatinine clearance fell to 62 ml/min. Computed tomography demonstrated significant enlargement of the right kidney and a thrombus in the right renal vein which extended cranial into the inferior vena cava. High dosage infusion of urokinase (4.5-7.5 mill. IU daily for nine days) achieved complete lysis of the thrombus. The creatinine concentration fell to 1.1 mg/dl, while creatinine clearance rose to 104 ml/min. On the 5th day the right kidney had 25% of total function, several days later 40%.--This case illustrates that, as long as there are no contraindications, adequately high doses of urokinase can be appropriate treatment of acute renal vein thrombosis associated with the nephrotic syndrome. |