Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1948070 | Structures of free and inhibited human secretory phospholipase A2 from inflammatory exudat | 1991 Nov 15 | Phospholipase A2 (PLA2) participates in a wide range of cellular processes including inflammation and transmembrane signaling. A human nonpancreatic secretory PLA2 (hnps-PLA2) has been identified that is found in high concentrations in the synovial fluid of patients with rheumatoid arthritis and in the plasma of patients with septic shock. This enzyme is secreted from certain cell types in response to the proinflammatory cytokines, tumor necrosis factor or interleukin-1. The crystal structures of the calcium-bound form of this enzyme have been determined at physiological pH both in the presence [2.1 angstrom (A) resolution] and absence (2.2 A resolution) of a transition-state analogue. Although the critical features that suggest the chemistry of catalysis are identical to those inferred from the crystal structures of other extracellular PLA2s, the shape of the hydrophobic channel of hnps-PLA2 is uniquely modulated by substrate binding. | |
| 1937754 | Involvement of interleukin-1 (IL-1), IL-6, IL-2, and IL-4 in generation of cytolytic T cel | 1991 Nov | The capacity of Mycoplasma fermentans-derived high-molecular-weight material (MDHM) to generate cytolytic T cells from mitogen-stimulated murine thymocytes was studied in detail. The role of MDHM and the involvement of monokines and lymphokines resulting from the addition of MDHM to thymocyte cultures were examined in complete and adherent cell-depleted culture systems by the addition of neutralizing monoclonal antibodies against interleukin-2 (IL-2), IL-4, and IL-6 and in reconstitution experiments with recombinant mediators. The data presented here suggest that MDHM is crucial only in the first phase of a reaction sequence beginning with the stimulation of adherent accessory cells and resulting in the synthesis of IL-1 and IL-6. The lymphokines IL-2 and, primarily, IL-4 are required in a second step which, once these lymphokines are formed, can proceed in the absence of MDHM and accessory cells and leads to the formation of cytolytic T cells. The elucidation of the MDHM-induced reaction sequence may be of relevance in view of the hypothetical role of mycoplasmas in rheumatic disease in humans. M. fermentans is an organism capable of infecting humans and in an early report has been discussed as a causative agent for rheumatoid arthritis. | |
| 1777755 | The prevalence of cognitive impairment in a community survey of multiple sclerosis. | 1991 Nov | A one in two alternate sample (N = 200) from a population-based register of 411 people with multiple sclerosis (MS) was studied. Out of this sample, 147 people with MS and 34 people with rheumatoid arthritis were interviewed at home and completed a battery of neuropsychological tests. Cognitive impairment was found in 46 per cent of those with MS, with memory impairment in 34 per cent and failure on tests of frontal lobe function in 33 per cent. Physical disability was associated with cognitive impairment. Memory impairment was more common in those who had had MS for 10 years or more. A significant minority of people with mild physical disability and some who had had MS for less than a decade nevertheless had cognitive impairment. Relationships between cognitive impairment, other disease variables and psychosocial factors were examined. Counselling and rehabilitation programmes for people with MS and their families should take account of cognitive deficits that may be present. | |
| 1758370 | [Alpha-1-acid glycoprotein in differential diagnosis of rheumatic diseases]. | 1991 Oct 15 | In recent years, the investigation of acute-phase proteins with the aid of affinity electrophoresis employing lectins as carrier substance, has become ever more important, in particular in the diagnosis of inflammatory rheumatic diseases. In order to investigate the usefulness of a determination of alpha-1 glycoprotein microheterogeneity in the sera as a diagnostic parameter, we evaluated, on a prospective basis, the sera of 85 consecutive patients presenting at our department with various inflammatory rheumatic diseases (chronic rheumatoid arthritis [RA] [n = 22], seronegative spondarthropathies [SpA] [n = 15], polymyalgia rheumatica [PMR] [n = 10], polymyositis dermatomyositis [PM/DM] [n = 8], osteoarthritis [n = 18], and infectious diseases [n = 12]). The results were expressed as reactivity coefficient of the alpha-1 acid glycoproteins (AGP/RC). A significant increase in the AGP/RC was observed in patients with various infections, and in those with RA or SpA with intercurrent infection, as compared with patients with RA or SpA with no intercurrent infection, or in healthy controls. It also proved possible to differentiate between PM/DM and PMR. Determination of the erythrocyte sedimentation rate, and quantification of the C-reactive protein and of alpha-1 glycoprotein, permitted no discrimination between an increase in inflammatory activity related to the basic disease, and an intercurrent bacterial infection. The results show that the determination of qualitative changes in the acute phase proteins, in particular alpha-1 acid glycoproteins, may make it possible to differentiate between inflammatory and infectious diseases. This examination technique may be of future clinical importance. | |
| 1914227 | Urinary IL-6: a marker for mesangial proliferative glomerulonephritis? | 1991 Oct | A prospective study of plasma and urinary interleukin-6 (IL-6) levels was performed in 54 patients undergoing renal biopsy to determine whether detectable urinary IL-6 was a reliable marker for mesangial proliferation. Interleukin-6 was found in both the urine and plasma of seven patients, the urine alone of 15 patients, and the plasma alone of two patients. Interleukin-6 was not detected in the urine or the plasma of the remaining 30 patients, the urine of 10 healthy controls or the urine of 10 patients with rheumatoid arthritis with raised plasma IL-6. Interleukin-6 was found in the urine of only one out of an additional seven patients with lupus nephritis. Urinary IL-6 was associated with a variety of renal abnormalities and was not restricted to those with mesangial hypercellularity. Furthermore, many patients with mesangial hypercellularity did not have detectable urinary IL-6. There was no correlation between urinary IL-6 and plasma IL-6, urinary albumin excretion or urinary creatinine. These results suggest that IL-6 detected in the urine is a marker of renal IL-6 production, but not specifically of mesangial hypercellularity. The patients with IL-6 in the urine had a mean serum creatinine significantly higher than those without IL-6. It is not possible to distinguish at present whether IL-6 contributes to renal dysfunction or whether it reflects renal damage. | |
| 1657271 | Vasculitic neuropathy. A clinical and pathological study. | 1991 Oct | The clinical, electrophysiological and pathological features and prognosis of 34 patients with peripheral neuropathy caused by necrotizing vasculitis were evaluated. The causes included polyarteritis nodosa and its Churg-Strauss variant, rheumatoid arthritis, undifferentiated connective tissue disease, Wegener's granulomatosis, primary Sjögren's disease, and chronic lymphocytic leukaemia with cryoglobulinaemia; 2 patients had no evidence of systemic vasculitis. Mononeuritis multiplex was the most common clinical manifestation, followed by asymmetrical polyneuropathy and distal symmetrical polyneuropathy. Pain was a frequent symptom. Nerve conduction studies were abnormal in all cases, and in 3 patients there was conduction block or severe slowing of motor conduction. Necrotizing vasculitis was present in sural nerve biopsies of most cases, and severe active axonal degeneration was a dominant feature. Immunofluorescent staining of blood vessels for immunoglobulin, C3 and fibrinogen was positive in all cases in which it was performed, even when there was no cellular infiltration. All patients were treated with prednisone alone or in combination with other immunosuppressive agents, or with plasmapheresis. Long-term follow-up studies demonstrated that although the peripheral neuropathy usually improved and caused only mild to moderate functional disability, the long-term prognosis of the systemic disease was poor with a 5-yr survival of only 37%. | |
| 2128070 | Experience with a gastrointestinal marker (51CrCl3) in a combined study of ileal function | 1990 Oct | Introduction of a radioactive gastrointestinal marker (51CrCl3) into a combined study (75SeHCAT + 58CoB12) of ileal function by whole body counting has been undertaken. The technique was assessed in 23 subjects (15 patients with inflammatory bowel disease, six on non-steroidal anti-inflammatory drugs for rheumatoid arthritis, and two normal subjects). Mean (SD) 51CrCl3 retention was only 4.1 (6.0)% on day 4, and was similar on day 7 in subjects given a second dose of 51CrCl3 on day 4. Only one subject had more than 20% of 51CrCl3 retention after four days. A 51CrCl3 correction method adequately corrected for colonic hold up of 58CoB12, when compared with final equilibrium values of 58CoB12 retention. Use of the non-absorbed 58CoB12 fraction as a gastrointestinal marker gave good agreement with the 51CrCl3 method in correcting 75SeHCAT values. In all subjects studied, corrections for colonic retention of 75SeHCAT on day 4, were small (less than 7% of dose) and did not affect the assessment of any subject. In conclusion, an additional gastrointestinal marker such as 51CrCl3 is unnecessary in our combined study since that role can be effected, when indicated by the non-absorbed 58CoB12 fraction. | |
| 2354388 | Computed tomography of wrist trauma. | 1990 Jun | We devised a rapid and sensitive computed tomography (CT) method to assess the acutely injured wrist, healing carpal fractures and post-traumatic osteonecrosis, when the plain films offer insufficient information. The wrist is positioned in a simple reverse-L-shaped Perspex immobilizer. With the scaphoid as the center of the arc and the long axis of the distal radius as the reference 0 degrees line, sequential coronal scans of the wrist were done in 10 degrees increments in an arc of 40 degrees to give 0 degrees, 10 degrees, 20 degrees, 30 degrees and 40 degrees scans. The 0 degrees and 10 degrees arc scans were best for evaluating the distal radius and ulna and soft tissues, the 10 degrees and 20 degrees scans for the carpal bones other than the scaphoid, and their relation to each other, the 30 degrees and 40 degrees scans, parallel to the long axis of the scaphoid, for fractures of the scaphoid and the hook of the hamate. In addition the 40 degrees scan offered an excellent carpal tunnel view. In 22 patients examined for wrist trauma CT was found to be more accurate than plain films and plain-film tomography in determining the presence of a fracture (4 scaphoid and 1 distal radius), in assessing the degree of osseous union (12) and in evaluating intercarpal fusion (2). In addition CT detected avascular necrosis of the lunate in two patients and erosions of the scaphoid and distal radius attributed to rheumatoid arthritis in one. | |
| 2323824 | Cross-reactivity and sequence homology between the 65-kilodalton mycobacterial heat shock | 1990 May | Immunogold ultracytochemistry and Western immunoblotting showed that polyclonal antibodies against human lactoferrin bind to the highly immunogenic 65-kilodalton (kDa) heat shock protein of mycobacteria. The fast-growing mycobacterial species Mycobacterium smegmatis showed a higher density of these receptors for antilactoferrin sera than the slow-growing M. avium. Polyclonal antibodies against mycobacteria (M. bovis BCG) recognized human lactoferrin. Comparison of the amino acid sequence of lactoferrin with that of the 65-kDa protein of M. tuberculosis revealed seven instances of four amino acid sequence homology between the microbial and the human iron-binding protein. Four of these tetrapeptide sequences were also shared with the human transferrin molecule. The shared amino acid sequence KDLL was also present in the DR1, DR3, and DR4 subsets of the DR beta subregion of major histocompatibility complex (MHC) class II molecules. The molecular mimicry between the 65-kDa mycobacterial protein and the human proteins (lactoferrin, transferrin, and MHC class II molecules) offers a molecular setting for mycobacteria-associated, T-cell-dependent autoimmune disease, namely, for rheumatoid arthritis. | |
| 2624664 | Antibodies to extractable nuclear antigens in connective tissue disorders in India: preval | 1989 Dec | Antibodies to Extractable Nuclear Antigens (ENAs) namely Sm, nRNP, SS-A and SS-B were studied in 397 patients with various connective tissue diseases (CTD), 146 patients with inflammatory polyarthropathies, 16 cases of systemic vasculitides, and 39 normal subjects using counterimmunoelectrophoresis and double immunodiffusion methods. Anti-ENA antibodies were positive in 40.8 percent cases of Systematic lupus erythematosus (SLE) (n = 191), 36.4 percent of overlap CTD (OCTD, n = 44), 27.8 percent of Sjogren's syndrome (n = 18), 10.6 percent of progressive systemic sclerosis (PSS, n = 66) and 2.7 percent of rheumatoid arthritis (n = 111) patients. The correlation of these antibodies with disease features was done. The significant finding was negative association of anti-nRNP antibodies (when present alone) with renal involvement. Anti-Sm antibodies did not correlate with any disease feature. The other associations included correlation of anti-nRNP with pulmonary parenchymal lesions, anti-SS-A with serositis and pulmonary hypertension, and anti-SS-B with myocarditis and recurrent diarrhoea. We conclude that Anti-ENAs may correlate with certain subsets of these diseases but the subject is controversial. | |
| 2533339 | Validation of an observation method of pain assessment in non-chronic back pain. | 1989 Dec | An observation method for assessing chronic pain in back pain and rheumatoid arthritis has been developed during the last decade in the U.S.A. This study examined the validity and reliability of the method for a non-chronic back pain population from another culture. Two trained observers recorded pain behaviors displayed by 61 Swedish subjects during a 10 min, videorecorded, standardized sequence of maneuvers. Subjects were asked to make ratings of their pain intensity, depression, helplessness and disability level. A physical examination was performed by an orthopedist to obtain objective medical information about the subjects. Results showed that interrater as well as test-retest reliability were satisfactory. Correlations between pain behavior and other measures of pain, e.g., intensity ratings, medication intake, and spinal mobility, were statistically significant but somewhat lower than expected. The results indicate that the behavioral observation method provides reliable and valid information about non-chronic back pain among Swedish females. However, some modifications in the standardized sequence of maneuvers and the definitions of pain behaviors may be necessary to improve the utility of the method in this population. | |
| 2542168 | Effect of eicosapentaenoic acid rich menhaden oil and MaxEPA on the autoimmune disease of | 1989 | The Mrl lpr/lpr (Mrl/l) mouse is a model for systemic lupus erythematosus and rheumatoid arthritis in humans. The diet of Mrl/l mice was supplemented with EPA (see Introduction) in menhaden oil or in the commerical fish oil MaxEPA. The survival of mice was not affected by the dietary manipulations. The addition of menhaden oil decreased the severity of the renal pathology. However, MaxEPA containing the same amount of eicosapentaenoic acid was considerably less effective. A diet deficient in polyunsaturated fatty acids did not ameliorate any manifestations of the disease. Anti-DNA antibody levels in serum were not influenced by the therapy. Myocardial abscesses and/or ulcerating valvular lesions were observed in about one third of the mice, irrespective of the diet given. | |
| 2456062 | Inhibition of production of macrophage-derived angiogenic activity by the anti-rheumatic a | 1988 Jul 15 | We have investigated the effect of gold sodium thiomalate and auranofin, gold compounds employed in the treatment of rheumatoid arthritis, on production of macrophage-derived angiogenic activity. Elicited mouse peritoneal macrophages were cultured in the presence or absence of gold compounds or thiomalic acid, and the macrophages or their conditioned media were then assayed for their angiogenic activity in rat corneas. Control macrophage conditioned medium was potently angiogenic. In contrast, conditioned medium from gold or thiomalic acid treated macrophages was not. Addition of gold compounds or thiomalic acid to control macrophage conditioned medium did not inhibit its angiogenic activity. Drug treatments did not significantly affect macrophage lactate dehydrogenase release, lysozyme release, or protein synthesis. We conclude that gold sodium thiomalate and auranofin potently reduce the detectable angiogenic activity produced by macrophages. | |
| 2980792 | Metallothionein gene expression in mouse tissues by D-penicillamine. | 1988 Mar | The effect of D-penicillamine on metallothionein mRNA accumulation was examined in mouse tissues by Northern and dot blot analysis. This drug was given as a single intraperitoneal dose of 250 mg/kg body weight and the metallothionein mRNA content of the tissues was measured 1, 4, 8 and 24 hours later. A detectable increase of mRNA was observed after 1 hour and maximal accumulation was seen after 4 hours in the liver, kidneys, lungs, brain and spleen, whereas in the heart the maximum occurred after 8 hours. In the liver metallothionein mRNA was increased 14.5-fold over the control and in the kidneys it was increased by a factor of 9.2. A significant increase was also seen in the lungs, where it was 10 fold. To determine whether the increase is due to new transcription of the metallothionein gene, animals were pretreated with actinomycin D (1.0 mg/kg body weight) before receiving D-penicillamine. Actinomycin D prevented some of the D-penicillamine-induced increase in metallothionein mRNA, indicating that the drug, to some extent, acts at the transcriptional level. Regulation of metallothionein gene expression may play an important role in the molecular mechanisms involved in the clinical action of D-penicillamine in rheumatoid arthritis. | |
| 3216294 | Lack of relation between human T-lymphotropic virus type I infection and systemic lupus er | 1988 | To determine whether systemic lupus erythematosus (SLE) is associated with human T-lymphotropic virus, type I (HTLV-I) infection in Jamaica, an endemic area for the virus, we studied 63 patients with SLE at the University Hospital of the West Indies in Kingston. Antibodies to HTLV-I were measured by an enzyme-linked immunosorbent assay (ELISA) technique using purified disrupted whole virus as antigen, with confirmation by p24 protein RIA or competitive binding. Four of 63 SLE patients were HTLV-I seropositive (6.3%). There was no evidence for excess HTLV-I infection in SLE patients when their age- and sex-standardized HTLV-I seroprevalence rate was compared to that of a large group of healthy food service employees. None of 13 patients with rheumatoid arthritis were seropositive for HTLV-I. We conclude that HTLV-I infection does not appear to be linked with SLE in Jamaica. | |
| 3122369 | The effect of sodium aurothiomalate (myochrysin) on the distribution of calcium, magnesium | 1987 Dec 14 | Sodium aurothiomalate was given to male Wistar rats (initial body weights: 150 g) by subcutaneous (s.c.) injection at doses of up to 7.5 mg/kg (corresponding to 4.27 mg gold/kg), twice a week, for 4-5 weeks. The concentrations of Ca, Mg, Fe, Cu and Zn were measured in serum, urine, faeces and in the liver, kidney, spleen, heart, lung, testis, bone and muscle. Kidney cytosol was separated by gel chromatography and the fractions analysed for protein, copper, zinc, iron and gold concentrations. The concentration of copper was increased 5-fold in kidney while smaller increases of zinc in kidney, copper in muscle, iron in muscle and testis and calcium in spleen were found. There was a significant reduction in the concentration of copper in serum. Kidney cytosol from gold-treated but not from control animals contained a low molecular weight protein which was associated with copper, zinc and gold. The rats developed proteinuria and microscopic changes to renal tubular cell structure were also observed. It is suggested that the gold-induced accumulation of copper may follow from an increased rate of synthesis of metallothionein and could be responsible for the renal dysfunction which develops in a proportion of rheumatoid arthritis patients who are treated with gold. | |
| 3118007 | Gold disposition in the rat: studies of its plasma half-life and its urinary, biliary and | 1987 Oct | The biologic half-life of gold, a subject of controversy for many years, was found to be much longer in the rat than that reported for other species in the bulk of the literature. The longer observed half-life supports recent findings in man and is more consistent with the monthly maintenance dosing normally used in patients with rheumatoid arthritis. Excretion studies revealed that, after administration of gold sodium thiomalate, gold was eliminated via urinary and fecal pathways by approximately a 2:1 ratio. The relative importance of these pathways was not altered after multiple dosing. Biliary and intestinal excretion studies were performed to identify the means by which gold is eliminated via the feces. Only a small percentage of the dose was recovered from the bile after 2 hr, and biliary excretion was shown to be dose dependent. Results suggest that passive diffusion may be responsible for plasma-to-bile transfer and stand in contrast to the results of similar studies on other metals. Administration of gold as gold chloride [Au(III)] instead of gold sodium thiomalate [Au(I)] did not alter the excretion into bile, nor did stimulation of metallothionein, a metal-binding protein in the liver and kidney, by Cd pretreatment. Intestinal excretion was shown to be an insignificant pathway of gold elimination. The results of these studies suggest that, at high doses, gold-binding sites on plasma proteins may be saturated, resulting in an increase in excretion into the urine and bile, as well as an increase in distribution to peripheral tissues where tissue binding results in an overall increase in half-life. | |
| 2820320 | Isolation and analysis of immune complexes from sera of patients with polymyalgia rheumati | 1987 Jun | Serum samples were obtained from patients with polymyalgia rheumatica (PMR: n = 10) or giant cell arteritis (GCA; n = 7), or both. Samples were taken either before treatment or within one week of starting prednisolone. Immune complexes (IC) were concentrated by polyethylene glycol (PEG) precipitation then purified with either IgG anti-C1q-Sepharose or IgG anti-C3c-Sepharose. Complex components were separated by sodium dodecyl sulphate (SDS) gradient polyacrylamide gel electrophoresis then transferred to nitrocellulose by Western blotting. Identification of proteins was carried out using specific antisera. All the IC contained IgM (mu chain), some contained IgA (alpha chain), and IgG (gamma chain). C1r, C1s, C1q, C3, C4, and C reactive protein (CRP), where tested, were found in most but not all IC. The occurrence of properdin, factor B, alpha 2 macroglobulin (alpha 2M), factor H (beta 1H), C1 esterase inhibitor, and C4 binding protein was also investigated. Immune complexes in PMR and GCA differed from those previously characterized in rheumatoid arthritis (RA)1 purified by anti-C1q-Sepharose which contained immunoglobulins and C1q only. No properdin or factor B were detected in RA IC purified with either anti-C1q-Sepharose or anti-C3c-Sepharose. | |
| 3812465 | Role of immune stimulation in the etiology of multiple myeloma: a case control study. | 1987 Feb | A hospital-based case-control study of 153 multiple myeloma (MM) cases and 459 controls was conducted to evaluate the hypothesis that chronic or frequent infections or allergic and autoimmune diseases might be of higher prevalence in individuals who develop MM. Information was obtained by direct interviews of subjects. Controls were matched to cases on age, sex, race, and hospital. "Immune-stimulating conditions" included chronic infections such as pyelonephritis, urinary tract infections (UTIs), prostatitis, rheumatoid arthritis and other collagen vascular diseases, allergies, bronchitis, tuberculosis, cholecystitis, diverticulitis, and osteomyelitis. The overall odds ratio (OR) (odds of history of immune-stimulating conditions in cases versus controls) was 0.4 (95% confidence interval = 0.3-0.7) which suggested that cases had significantly less immune-stimulating conditions than did controls. The exposure rate for these conditions was high for cases (0.7) as well as for all control groups (0.8). These findings suggest that immune-stimulating conditions alone are not the causative factor in the etiology of MM, though they may play a role in the predisposed individual. | |
| 3606352 | Long-term study of the peroperative infection rate in 1007 total hip replacements using pr | 1987 | Of 1824 primary total hip replacements performed between April 1, 1979, and December 31, 1983, 1007 were reviewed at regular interval and provided sufficiently complete data with special emphasis on pre- and postoperative bacteriological examination and pre- and postoperative determination of the erythrocyte sedimentation rate. All patients with known superficial and deep infections were included. In all cases 2 g of cefamandole q.i.d. were administered within a 24-h period starting with the induction of the anesthesia. All procedures were performed in operating rooms equipped with a vertical laminar air flow. Other precautions included the use of Charnley gowns with a body exhaust system, special draping of the patient, and preoperative culture of the urine. As of June, 1981, gentamicin-loaded polymethylmetacrylate was used routinely. When positive cultures were found in the swabs taken from the tissues during the surgical procedure, appropriate antibiotics were started if the patient was still hospitalized. Follow-up showed two deep (0.2%) and four superficial infections (0.4%). Host factors may play a more important role than suspected, since one patient with a deep infection suffered from severe rheumatoid arthritis and the other from diabetes. Both these patients underwent bilateral hip replacement, the second intervention following the first within 5 weeks. In these two patients the deep infection became apparent 5 and 9 months after the second procedure. Only one of these patients developed a sinus (Staphylococcus aureus).(ABSTRACT TRUNCATED AT 250 WORDS) |