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

ID PMID Title PublicationDate abstract
9018246 Visualization of silicone gel in human breast tissue using new infrared imaging spectrosco 1997 Feb Between 1 and 2 million women in the United States have silicone breast implants. Complications include capsular contracture and calcification and possibly connective tissue diseases such as scleroderma and rheumatoid arthritis, a subject of some controversy. In order to accurately assess the role of silicone in any histopathologic change, it is necessary to confirm its presence and to identify other foreign materials in the capsular tissue. Although light microscopy is used to visualize regions of tissue containing foreign inclusions, their chemical identity can only be determined using analytical techniques such as infrared or Raman microscopy. However, these conventional microprobe techniques record spectra only at single points and require an a priori knowledge of the locations of the inclusion to be probed. To significantly extend the capabilities of both infrared spectroscopy and optical microscopy, we have developed a new infrared imaging system that completely integrates these two methods. In this manuscript we highlight the ability of the technique to screen rapidly and to determine accurately the presence, size and chemical composition of silicone gel inclusions in human breast tissue.
14569758 Risk factors for infection in total knee replacement surgery at hospital Kuala Lumpur. 2001 Dec One hundred primary TKR surgeries done between January 1994 and December 1999 were reviewed after a mean follow-up of 37.4 months. The rate of superficial and deep wound infection were 2% and 9% respectively. The most common organism in wound infection was Staphylococcus aureus. The factors that were significantly associated with superficial wound infection were diabetes mellitus (p = 0.005) and Rheumatoid arthritis (p = 0.0000). The factors that were significantly associated with deep wound infection were diabetes mellitus (p = 0.000). There was no significant difference between duration of surgery, and the mean age among patients with and without wound infections.
9648328 Private body consciousness, anxiety and pain symptom reports of chronic pain patients. 1998 May An information processing model of pain symptom perception and reporting predicts that individuals prone to high levels of attentional self-focus and negative affect will report more pain than individuals low in these characteristics. Past research on college student and medical patient samples has shown that individuals high in private body consciousness (PBC), or attentional self-focus and who report higher levels of anxiety report more pain symptoms than counterparts low in PBC and anxiety. The present study examined effects of PBC and anxiety on pain reports of individuals suffering chronic pain (N = 144). Pain patients suffering chronic headache, low back pain, rheumatoid arthritis and fibromyalgia were included in the sample. A non-pain control sample (N = 31) was also studied to examine potential differences between controls and pain patients. Results indicated that pain patients reporting high levels of PBC reported more pain, although the effects of anxiety on pain reports among pain patients was not significant. Controls did not differ from pain patients on PBC, nor did the 4 groups of pain patients differ on PBC, suggesting PBC is a dispositional variable. Implications for the importance of attentional self-focus in pain symptom reporting are discussed.
9445399 Intercellular calcium signalling between chondrocytes and synovial cells in co-culture. 1998 Feb 1 Intercellular communication allows the co-ordination of cell metabolism between tissues as well as sensitivity to extracellular stimuli. Paracrine stimulation and cell-to-cell coupling through gap junctions induce the formation of complex cellular networks that favour the intercellular exchange of nutrients and second messengers. Heterologous intercellular communication was studied in co-cultures of articular chondrocytes and HIG-82 synovial cells by measuring mechanically induced cytosolic changes in Ca2+ ion levels by digital fluorescence video imaging. In confluent co-cultures, mechanical stimulation induced intercellular Ca2+ waves that propagated to both cell types with similar kinetics. Intercellular wave spreading was inhibited by 18alpha-glycyrrhetinic acid and by treatments inhibiting the activation of purinoreceptors, suggesting that intercellular signalling between these two cell types occurs both through gap junctions and ATP-mediated paracrine stimulation. In rheumatoid arthritis the formation of the synovial pannus induces structural changes at the chondrosynovial junction, where chondrocyte and synovial cells come into close apposition: these results provide the first evidence for direct intercellular communication between these two cell types.
11771525 Japanese generalised osteoarthritis was associated with HLA class I--a study of HLA-A, B, 2001 To investigate the association between generalised osteoarthritis (GOA) and HLA-A, B, Cw, DQ and DR, we typed for HLA in 72 Japanese patients with GOA and compared with those of 1480 normal controls. The antigen frequency of HLA-Cw4 was significantly higher in the GOA group than in the control group. That of B62 was higher, but only uncorrected P values were significant. Those of HLA-Cw1 and Cw10 were significantly lower in the GOA group than in the control group. The antigen frequencies of HLA-DRB1*0101, *0401, *0405, *1001, and *1402, which were reported to be associated with rheumatoid arthritis, in the GOA group were not significantly different from those in the control group. The present study provides evidence of a significant association between Japanese GOA and HLA, which is different from that of Japanese RA. This may suggest that an immunological reaction that is different from RA plays a role in the pathogenesis of GOA.
11320858 [Nitric oxide and gastroduodenal damage caused by NSAIDs. Recent findings and clinical imp 2001 Mar A significant role of nitric oxide (NO) is being acknowledged gastroduodenal mucosa defense mechanism(s) against the injurious effect of NSAIDs. Many of the NO effects recall those of prostaglandins, such as direct protection of epithelial cells, mucus release, repair of mucosal erosions or ulcerations, mast cell degranulation. Other co-effects prove to be the inhibition of neutrophil adherence to the vascular endothelium, also associated with an improved mucosal blood flow. NO may also act by scavenging oxygen-derivedfree radicals. Consequently, in order to reduce the NSAID gastrotoxicity has been proposed: a) the linking of a NO-releasing mojety to these agents (NSAID NO-donors); b) the use of amtolmetin guacyl (AMG), a drug which induces an increase in the gastric mucosa NO concentration via direct stimulation of the local endogenous synthesis of this gas. Clinical studies on the efficacy and tolerability have been carried out with AMG versus other NSAIDs (diclofenac, indomethacin, piroxicam, naproxen) in patients with osteoarthritis, rheumatoid arthritis and a number of post-traumatic arthropathies. As far as clinical symptoms are concerned AMG proves to be equally effective, but significantly better as far as gastroscopic lesions are concerned. NONSAIDs and AMG may play an important role among the long-term treatment of chronic inflammatory osteoarticular and rheumatic diseases.
11264779 Dynamic of beta(2)-microglobulin fibril formation and reabsorption: the role of proteolysi 2001 Mar Dialysis-related amyloidosis (DRA) is caused by the deposition, in target tissues, of beta(2)-microglobulin (beta(2)M) in fibrillar conformation. Several reports indicate that fibrillar beta(2)M is chemically heterogeneous and such heterogeneity is partially related to the presence of truncated species of the protein. In association with the full-length species, a beta(2)M isoform lacking six N-terminal residues is present in all the samples of our collection of ex vivo fibrils. The pattern of proteolytic cleavage in amyloidosis and in other diseases is completely different, as demonstrated by the absence in fibrillar beta(2)M of the cleavage at lysine 58, which is contrary to that described in rheumatoid arthritis and other diseases. The role of limited proteolysis of beta(2)M in the pathogenesis of the disease is uncertain. However, we have shown that the apparently minor modification of the intact protein, such as the removal of N-terminal hexapeptide, is capable of dramatically affecting its stability, protection from proteolytic digestion, and enhance its capacity to make in vitro amyloid fibrils. The structure, folding dynamic, and function of the truncated species of beta(2)M, peculiar of DRA, could shed new light on the mechanism of beta(2)M fibril formation and reabsorption.
11037336 Significance levels in genome scans. 2001 Genome-wide linkage scans using affected sibpair families are being conducted on many complex diseases, such as type 1 and type 2 diabetes, multiple sclerosis, rheumatoid arthritis, schizophrenia, asthma, cardiovascular diseases, obesity, and alcoholism. Despite extensive efforts by many groups, progress has been exceedingly slow, and only a few genes and some genomic regions involved in complex diseases have been identified. The general picture is one of difficulty in locating disease genes and replication of reported linkages. This results from the fact that complex diseases and traits may result principally from genetic variation that is relatively common in the general population involving a large number of genes, environmental factors, and their interactions. Genome-wide association studies are now feasible through the use of PCR methodologies with pooled DNA samples and microsatellite variation, and more recently single-nucleotide polymorphism (SNP) variation. Issues relating to significance levels in genome-wide linkage and association scans are discussed, and suggestions for dealing with false positive (type I) errors proposed.
11033918 Treatment of osteoarthritis of the knee with valgus deformity by means of varus osteotomy. 2000 Jun Nineteen cases of osteoarthritis of the knee with valgus deformity in 17 patients were treated by femoral supracondylar varus osteotomy (17 cases) or by high tibial varus osteotomy (2 cases) over the last 15 years. Fixation was performed using a 95 degrees AO blade-plate in 13 of the femoral osteotomies and a straight plate in the other four. The mean follow-up time was 6.5 years. The valgus deformity was idiopathic in 14 cases, secondary to rheumatoid arthritis in 2 cases and to tibial valgus in one case. The Hospital for Special Surgery (HSS) score was used to evaluate the clinical results: nearly 75% were excellent or good. The causes related to poor results are analyzed regarding indication and surgical technique. It appears that varus osteotomy is an effective procedure for the treatment of osteoarthritis of the knee with valgus deformity, above all in order to alleviate pain, although the operation requires precision, and correct selection of patients is of prime importance.
11111803 Sudden death caused by myocardial tuberculosis: case report and review of the literature. 2000 Dec A 25-year-old fit man died suddenly while playing social soccer. Autopsy revealed an infiltrative lesion involving the left ventricle with overlying pericarditis. No other significant pathologic changes were observed. Histologic examination showed necrotizing granulomatous inflammation. No acid-fast bacilli were demonstrated in the pericardial fluid or on histologic examination. The presence of Mycobacterium tuberculosis DNA complex was confirmed by use of the ligase chain reaction technique. The differential diagnosis of myocardial tuberculosis includes sarcoidosis, rheumatic fever, rheumatoid arthritis, giant-cell-containing tumors, idiopathic (giant-cell) myocarditis, and bacterial infections such as tularemia and brucellosis. This case illustrates the protean manifestations of tuberculosis and highlights the use of molecular biologic techniques in arriving at a definitive diagnosis in cases of suspected tuberculosis.
10608507 Expression and function of serum amyloid A, a major acute-phase protein, in normal and dis 2000 Jan Serum amyloid A (SAA), the precursor protein in inflammation-associated reactive amyloidosis (AA-type), is an acute phase reactant whose level in the blood increases in response to various insults. It is expressed in the liver, but its physiological role is not well understood. Recently, a broader view of SAA expression and function has been emerging. Expression studies show local production of SAA proteins in histologically normal, atherosclerotic, Alzheimer, inflammatory, and tumor tissues. Binding sites in the SAA protein for high density lipoproteins, calcium, laminin, and heparin/heparan-sulfate were described. Adhesion motifs were identified and new functions, affecting cell adhesion, migration, proliferation and aggregation have been described. These findings emphasize the importance of SAA in various physiological and pathological processes, including inflammation, atherosclerosis, thrombosis, AA-amyloidosis, rheumatoid arthritis, and neoplasia. In addition, recent experiments suggest that SAA may play a "housekeeping" role in normal human tissues.
10408531 Matrix metalloproteinases in inflammatory demyelination: targets for treatment. 1999 Jul 13 Matrix metalloproteinases (MMPs) degrade all protein components of the extracellular matrix. Functionally, they contribute to several different physiologic conditions, such as angiogenesis or bone remodeling, as well as pathologic conditions in humans, such as rheumatoid arthritis and tumor growth. MMPs seem to be important in the pathogenesis of inflammatory demyelinating diseases of the central and peripheral nervous system, especially in MS and in Guillain-Barré syndrome (GBS). Key mechanisms in the genesis of inflammatory demyelination, such as leukocyte recruitment, blood-brain barrier or blood-nerve barrier breakdown, myelin destruction, and release of disease-promoting cytokines, are considered to be MMP-dependent processes. In experimental autoimmune encephalomyelitis, an animal model of MS, and experimental autoimmune neuritis, an animal model of GBS, different synthetic inhibitors targeting MMP activity are able to suppress and even reverse ongoing disease. This evidence points to MMPs as new targets for treatment in inflammatory demyelination.
10337936 Hypokalemia with syncope caused by habitual drinking of oolong tea. 1999 Mar A 61-year-old woman developed hypokalemia, atrioventricular block and ventricular tachycardia with syncope after habitual drinking 2 to 3 liters of oolong tea per day. She had been suffering from rheumatoid arthritis and Sjögren's syndrome and her serum albumin was decreased (2.9 g/dl). Oolong tea contains caffeine at approximately 20 mg/dl. Great quantities of caffeine can induce hypokalemia. The serum protein binding caffeine is albumin. Accordingly, in patients with hypoalbuminemia, caffeine is apt to induce hypokalemia. This case suggested that great quantities of oolong tea, one of the so-called "healthy" drinks, result in serious symptoms for patients with hypoalbuminemia.
25470681 Retinal pigment epithelial cell cultures as a tool for evaluating retinal toxicity in vitr 1999 May This article reviews in vitro testing of retinal toxicity in retinal pigment epithelium (RPE) cell cultures. It is based on the literature on RPE cell cultures and on our recent studies on the retinal toxicity of selected amphiphilic drugs. The RPE plays a major role in maintaining the homeostasis and health of the retina. Various pharmacological agents are known to cause adverse effects in RPE cells. For example, long-term treatment with chloroquine in patients with rheumatoid arthritis has induced retinopathy, and tamoxifen, a drug that is commonly used in the treatment of advanced breast cancer and in the prevention of breast cancer among high-risk women, has been reported to cause retinal changes and impaired vision. During our research, we have developed novel in vitro methods for evaluating the retinal toxicity of xenobiotics. We have used a pig RPE primary culture and a human RPE cell line (D407), which retain epithelial cell characteristics. They form a layer of hexagonal cells with intercellular junctions, and possess a keratin-containing cytoskeleton. They are both good models for determining the retinal cell toxicity of test compounds. Further studies on phagocytic activity, lysosomal enzyme activity and glutamate uptake might generate new methods for the toxicological evaluation of the retinal side-effects of drugs in vitro.
10050792 Coexistence of erythrocyte agglutination and EDTA-dependent platelet clumping in a patient 1999 Feb For 8 years, EDTA-dependent pseudothrombocytopenia was observed in a 55-year-old woman with a history of rheumatoid arthritis who had undergone surgery for lymphoepithelial thymoma 11 years earlier. The clinical picture was characterized by the presence of platelet clumps and antiplatelet antibodies of the IgM class. With the recent appearance of a solitary extramedullary plasmocytoma in the right retrobulbar region and the detection of an IgGlambda monoclonal gammopathy, blood examination also revealed erythrocyte agglutinates alongside the platelet clumps and the presence of a cold IgG antibody with antiI specificity. Both phenomena were observed in vitro when the sample temperature declined to 20 degrees C to 25 degrees C, but not at 37 degrees C. While the EDTA-dependent antiplatelet antibodies did not appear to be chronologically correlated with the patient's diseases, the cold antierythrocyte autoantibodies were strictly related to the plasmocytoma and the IgGlambda monoclonal component in serum. To our knowledge, this is the first description of an association between EDTA-dependent platelet and erythrocyte agglutinates, with a clinical picture of pseudothrombocytopenia and pseudoerythrocytopenia due to cold agglutinins.
9924204 An overview of rheumatological research in the European Union. 1998 Nov OBJECTIVES: To evaluate the distribution and scope of papers published by authors from the European Union (EU) in rheumatological journals and the impact of rheumatological research in the EU in comparison with that produced elsewhere. METHODS: Papers published during the year 1995 in the 17 rheumatological journals screened by ISI were considered. The journal impact factor (IF) was noted. All key words, both those reported by the authors and those attributed by ISI, were identified and their frequency was calculated using a special purpose program. RESULTS: 2331 papers were published in the rheumatological literature during 1995. Of them, 1316 (56.5%) came from the EU (29.4% from the UK, 17.4% from France, 11.5% from Germany, and 10.8% from Italy) and 544 (23.3%) from the USA. The mean IF of EU papers was approximately 2 in comparison with 3.5 for the USA and 2.4 for other countries. In 1995, 2680 key words attributed by the authors and 5651 attributed by ISI appeared in the rheumatological literature. Less than a quarter of them was cited more than twice. The leading key words were rheumatoid arthritis for diseases and methotrexate for drugs. CONCLUSIONS: Bibliometric findings are useful to follow research trends. These data show the relevance of EU rheumatological research and the high scientific production of small countries. Dispersion of key words should be avoided and journal editors should promote their standardisation.
29508817 Digoxin : a model for hypothalamic regulation of neuronal transmission, endocrine function 1998 Oct The case report of a family with coexistence of schizophrenia, systemic malignancy, Parkinson's disease, rheumatoid arthritis and syndrome X is described. The coexistence of malignant transformation, neuronal degeneration, immune dysfunction and psychiatric manifestation have been extensively documented in literature. It is possible that a central dysfunction in neuroendocrine and immune integration may play a role in the pathophysiology of these diseases. Elevated levels of an endogenous sodium-potassium ATPase inhibitor, digoxin, a steroidal glycoside, has been reported in syndrome X. The human hypothalamus is the principal source of digoxin. Serum digoxin level and RBC sodium-potassium ATPase were measured in the members of the index family and8 groups of patients with CNS gliomas, Parkinson's disease, motor neuron disease, CNS vasculitis, multiple sclerosis, primary generalised epilepsy, schizophrenia and the acquired immunodeficiency syndrome. Digoxin, being a isoprenoidal compound, its synthesis was assessed by HMG CoA reductase activity. The levels of serum digoxin and HMG CoA reductase activity were found to be increased in the members of the index family and all the 8 groups studied with a corresponding reduction in RBC sodium-potassium ATPase activity. The role of hypothalamic digoxin in the pathogenesis of these diseases is discussed. A digoxin model for hypothalamic regulation of neuronal transmission, endocrine function, immunity and cytodifferentiation is proposed.
9736218 Role of the T cell receptor in idiopathic thrombocytopenic purpura (ITP). 1998 Jun During the past few decades a number of studies has described T cell defects and attempted to elucidate their role in the pathogenesis of idiopathic thrombocytopenic purpura (ITP). Some studies implicate T cells as potential initiators of autoantibody production in ITP. However, only a few of these have studied the role that the T cell receptor may play in the pathogenesis of ITP. In a variety of autoimmune syndromes interest has focused on the alpha- and beta-chains of the T cell receptor. Deviations from the normal T cell receptor gene usage have been reported in rheumatoid arthritis, systemic lupus erythaematosus and multiple sclerosis. Usually, these studies have shown a restricted heterogeneity of T cell receptor variable gene usage. The studies on the T cell receptor in ITP have included a limited number of patients, which makes it difficult to evaluate the significance of the role that the T cell receptor may play in the pathogenesis of ITP. Further studies are warranted.
9304801 Nuclear factor-kappa B. 1997 Jun Nuclear factor-kappa B (NF-kappa B) is a ubiquitous transcription factor that, by regulating the expression of multiple inflammatory and immune genes, plays a critical role in host defence and in chronic inflammatory diseases. It is a heterodimer, present in the cytoplasm in an inactive form complexed to an inhibitory protein, I kappa B. Many extracellular stimuli, including viruses, oxidants, inflammatory cytokines and immune stimuli, activate NF-kappa B. Once activated, it binds to recognition elements in the promoter regions of inflammatory and immune genes, such as proinflammatory cytokines, chemokines, inflammatory enzymes and adhesion molecules. Glucocorticoids inhibit activated NF-kappa B and this is likely to be important in the anti-inflammatory action of steroids. Novel inhibitors of NF-kappa B are now under development for treatment of inflammatory diseases such as asthma, rheumatoid arthritis and inflammatory bowel disease.
9253772 [Multiple roles of inducible cyclooxygenase-2 and its selective inhibitors]. 1997 Jun Cyclooxygenase (COX) is the enzyme that catalyzes the conversion of arachidonic acid to prostaglandin endoperoxides. In addition to constitutive COX-1, inducible COX-2 has been discovered. COX-2 is induced not only in acute exudative rat carrageenin-induced pleurisy, but in granuloma formation/proliferative inflammation for the acceleration of angiogenesis. This means that COX-2 is induced in the healing process of wounds such as in granuloma of gastric ulcer and the proliferative stage of endometrium. COX-2 is also introduced in ovulation and parturition. Osteoblasts induce COX-2 to accelerate bone absorption. Induction of COX-2 in colon carcinoma is a recent, very exciting topic of investigation. We can learn about many unknown roles of COX-2 from its knockout mouse, but the results must be interpreted cautiously. Development of selective COX-2 inhibitors, such as NS-398, opened a new era in which the side effects of gastric and renal lesions by NSAIDs could be ignored. However, prolongation of would healing by the inhibitors and transient expression of COX-2 must be considered in medical intervention with selective COX-2 inhibitors. Nevertheless, acute exudative inflammation, granuloma formation and bone absorption in rheumatoid arthritis are good targets for these inhibitors and application of these inhibitors will be extended to dysmenorrhea, interruption of abortion and increasing survival rate of patients with colon carcinoma.