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

ID PMID Title PublicationDate abstract
7680295 Calreticulin synthetic peptide analogues: anti-peptide antibodies in autoimmune rheumatic 1993 Mar Autoantibodies in sera from patients with systemic lupus erythematosus (SLE) and onchocerciasis recognize calreticulin (CaR), a calcium-binding protein, as antigen. In this study we present the immunological properties of two synthetic peptides prepared to correspond to the 1-24 and 7-24 amino acid sequence of CaR. In contrast to information previously reported for the recombinant protein, the CaR-peptide analogues appeared immunoreactive to anti-Ro/SSA autoimmune sera. Human sera from patients with SLE, Sjögren's syndrome (SS), rheumatoid arthritis (RA), as well as mixed connective tissue disease (MCTD), demonstrated a positive autoimmune response (binding of antibodies), to the CaR-peptide analogues. These findings suggest that anti-calreticulin autoantibodies are not restricted to any disease specificity.
7513617 Lymphocyte-synovial cell interactions: a role for beta 1 and beta 3 integrin-mediated adhe 1993 Feb The interactions of lymphocytes with cultured synovial cells derived from rheumatoid arthritis patients were examined. A number of lymphoid cell lines bound to these cells. The adherence of several of these lines was inhibited by antibodies to fibronectin. The adherence of the T cell leukemia Jurkat was sensitive to inhibition by antibodies to the fibronectin receptors alpha 4 beta 1 and alpha 5 beta 1. The adherence of the beta 1 integrin negative B cell line RPMI 8866 was inhibited by antibodies to the vitronectin receptor, alpha v beta 3. The interactions of several other cell lines with synovial cells appeared to be independent of this fibronectin-dependent pathway. These results indicate that multiple potential adhesion pathways for cellular interactions in the tissues may exist. The adherence to cell-associated fibronectin may play a contributory role in such processes for certain lymphocyte subsets.
1280908 Case report: granulocyte colony-stimulating factor overcomes severe neutropenia of large g 1992 Dec Large granular lymphocytosis (LGL) is characterized by enhanced proliferation of T lymphocytes that have antibody-dependent cell-mediated cytotoxicity or natural killer cell activity and that often produce severe cytopenias, including neutropenia. When a 68-year-old man with seropositive rheumatoid arthritis and severe neutropenia was examined, he was found to have LGL with a T cell gene rearrangement, indicating the presence of a clonal population of T lymphocytes. The patient was admitted with a fever of 102 degrees F and a nonhealing ulcer over the right tibia. When the infection did not respond to intravenous antibiotics, granulocyte colony-stimulating factor (GCSF) therapy was started at 5 micrograms/kg subcutaneously each day. The neutrophil count promptly increased and the patient subsequently defervesced and was able to have a skin graft placed, which healed without difficulty. GCSF, which is known to be an effective therapeutic agent for neutropenia associated with chemotherapy and bone marrow transplantation, also was a very valuable treatment for the life-threatening neutropenia of LGL.
1642031 [Indications and technique of partial arthrodesis of the carpus]. 1992 May Partial arthrodesis of the carpus has again become a topical method. The technique has been improved and the range of indications has been extended. Fusion of certain areas has indeed been propagated as first-line therapy, for example in lunatum necrosis or as an important additional operation in substitution plastic surgery. Partial arthrodesis of the carpus is intended to eliminate mechanisms which has become pathological whilst preserving the best possible mobility. Partial arthrodesis alters the movement pattern of the individual ossae carpi. Moreover, the pressure in the adjacent joints also rises. The risk of a new pathological process is considerable. Recent publications report on a rapid development of impingement and symptoms. The most frequent partial arthrodeses are discussed. The indications and the direct consequences are critically analysed and explained with reference to examples. Technical details and potential dangers are described. An STT-arthrodesis is indicated for osteoarthritis of these bones. The radio-lunar arthrodesis is recommended for ulnar drifting of the carpus in cases of rheumatoid arthritis. Reconstruction of the central axis with arthrodesis of the capitate-lunate is indicated for pseudarthrosis of the scaphoid with carpal collapse. Other combinations are possible, they cause however greater functional deficits. We recommend a critical analysis of the function of the entire carpus before the operation. Caution is called for when an incipient arthrosis is present in the adjacent joint. Partial arthrodesis of the carpus is rather a temporary solution, since it enables time to be gained. Total arthrodesis is the ultimate resort.
1538434 Interstitial cystitis: increased sympathetic innervation and related neuropeptide synthesi 1992 Mar To investigate the possibility of a neural deterioration of the bladder wall in interstitial cystitis, bladder tissue from 10 patients with interstitial cystitis was compared with that from 10 control subjects by means of immunohistochemistry. An enhanced innervation of the bladder in the submucosa and detrusor muscle was found to represent an increase of sympathetic but not cholinergic neurons. In interstitial cystitis the number of neurons positive for vasoactive intestinal polypeptide and neuropeptide Y was higher and carried a larger number of axonal varicosities, whereas the number of neurons positive for substance P and calcitonin-gene-related peptide was not significantly different in both groups. We conclude that interstitial cystitis is associated with increased sympathetic outflow into the bladder and altered metabolism of vasoactive intestinal polypeptide and neuropeptide Y. Since similar changes have been observed in other inflammatory diseases of a presumably autoimmune nature, such as rheumatoid arthritis, Crohn's disease and colitis ulcerosa, the pathophysiology of interstitial cystitis may share common pathways with the latter. Experience in these diseases may facilitate a better understanding of the pathophysiology of interstitial cystitis and suggest new therapeutic concepts.
20065464 [Results of cultures and serotyping of S. pyogenes 1986-1993.]. 1995 Oct Streptococcus pyogenes is a major human pathogen. It is a common cause of pharyngitis, cellulitis and wound infections. Late complications like rheumatoid arthritis and glomerulonephritis are associated with certain M proteins on the surface of the bacteria. In 1987 an increase was noted in the incidence of serious infections caused by this bacterium. The increase has been associated with protein type M 1. Typing with antibodies against T proteins is simpler to perform than M typing and can give as good epidemiological information. Culture results from January 11986 to December 31 1993, from the Department of Microbiology at the National University Hospital in Reykjavik, were reviewed. T protein type of some of the strains, that had been preserved by freezing, was determined by agglutination after culture in Todd Hewitt broth as described by Efstratiou. T-protein type of 384 strains from 1991-1993 was determined and the results compared to unpublished results from 1988 and 1989. T-protein type was also determined on all S. pyogenes strains that were isolated from blood in 1989 to 1993. The following T-types were most common: 1988-1989 Tl vas 30%; 1991, T4 and T28 70% and 62% in 1992; in 1993 Tl and T3 were 59%. Thirty one strains were sent to the Streptococcal Reference Laboratory, Central Public Health Laboratory, London, for determination of M-proteins. All strains but one, that were sent to Britain for M-protein typing, had corresponding T-proteins (Mx=Tx; My=Ty and so on). Big fluctuations in the number of isolations of S. pyogenes strains was observed during the study period: Fewest in 1989 or 629, but the number was highest in 1993 or 2057. The changes in incidence seemed to correlate with certain serotypes.
8952665 [Cutaneous reactions to gold salts]. 1996 Oct 26 Gold salts are used for rheumatoid arthritis, and also in resistant corticosteroid dermatoses such as pemphigus. Gold salts inhibit the expression of endothelial cell adhesion molecules, but activity varies from one molecule to another; thiomalate alone gives the same effect. Patients given gold salts have as high risk of cutaneous reactions, and a provisional diagnosis of "gold dermatisis" is insufficient. The mechanisms of cutaneous reactions are unknown and vary according to the molecules. Smokers, HLA Bw35 patients and perhaps atopic states are more prone to gold drug reaction. Inflammation at the site of injections is frequent but with no consequence. Accumulation (chrysiasis) may be observed with long-term treatment. The main problem is its diagnosis as it may mimic numerous dermatoses. Immunological adverse events are the most frequently encountered. Pruritus is frequently observed, more often with oral salts. Exanthemas are common and may disclose an associated visceral disease. Drug hypersensitivity is rare, but severe. All these types necessitate drug interruption although prescription has been continued after development of pityriasis rosea-like and eczematous eruptions in some series without worsening. Lichenoid eruptions require withdrawal, but the skin disease may continue. Oral presentation is frequent, either as a taste abnormality, or as stomatitis. Contact dermatitis may flare in patients sensitized to gold. Rare non-immunological skin diseases have been also observed. Careful dermatological assessment correlated with an imputability method and search of visceral side-effects could lead to a better choice for the patient. Skin tests are not reliable.
8799688 Aceclofenac. A review of its pharmacodynamic properties and therapeutic potential in the t 1996 Jul Aceclofenac is a phenylacetic acid derivative with anti-inflammatory and analgesic properties similar to those of diclofenac. However, preclinical studies suggest that the potential of aceclofenac to cause gastrointestinal damage is less than that of diclofenac. Double-blind comparative trials indicate that the efficacy of aceclofenac is at least equivalent to that of ketoprofen and similar to that of indomethacin and diclofenac in patients with rheumatoid arthritis, similar to that of diclofenac and piroxicam in patients with osteoarthritis of the knee and similar to that of tenoxicam, indomethacin and naproxen in patients with ankylosing spondylitis. The analgesic efficacy of aceclofenac 100mg is more prolonged than that of paracetamol (acetaminophen) 650mg. If the apparently improved gastrointestinal tolerability of aceclofenac compared with diclofenac is confirmed by wider clinical experience, aceclofenac will have the potential to become a preferred initial drug in an individualised NSAID regimen in patients with rheumatic disorders.
8791849 Osteocalcin in canine joint diseases. 1996 Jul Markers of joint disease are much sought after in human and veterinary rheumatology. This study investigated the relationship between markers of bone and cartilage turnover in sera and synovial fluids in naturally occurring canine joint diseases. Osteocalcin (OC) was measured by radioimmunoassay; enzyme-linked immunosorbent assays were used to measure keratan sulphate, chondroitin sulphate, hyaluronan and antibodies to collagen I and II. Dimethylmethylene blue binding assay was used for the estimation of sulphated glycosaminoglycans. Compared to normal dogs significantly higher serum OC was seen in dogs with osteoarthritis (P < 0.005), rheumatoid arthritis (RA) (P < 0.01) and rupture/stretching of cranial cruciate ligament (P < 0.02). Reduced OC was found in RA synovial fluids but this finding is probably of little value as there was too much overlap with normal joint data. Apart from a weak correlation between synovial fluid OC and keratan sulphate, there were generally no correlations between markers of bone and cartilage turnover probably reflecting the lack of any relationship between bone and cartilage metabolism in most canine arthropathies.
8691183 Current concepts in postmenopausal hormone replacement therapy. 1996 Jul As more women are living longer, there is an increasing need for women to discuss hormone replacement therapy (HRT) with their physicians. This task is complicated by areas of scientific uncertainty and evolving data concerning the risks and benefits of HRT. Benefits of HRT that are supported by strong scientific evidence include relief from menopausal symptoms such as hot flashes, prevention of osteoporosis, cardioprotective effects, relief of urogenital atrophy, and decreased urinary incontinence. Benefits supported by observational evidence include improvement of emotional lability and depression, improved sense of well-being in patients with rheumatoid arthritis, increased dermal and total skin thickness, improved verbal memory skills, and decreased risk of colon cancer. Risks to consider include a possible increase in the incidence of breast cancer and an increase in endometrial cancer in women who have an intact uterus and do not receive a progestin. Women in various risk groups, such as those at risk for coronary artery disease, osteoporosis, or breast cancer, must consider the risk-to-benefit ratio for their own individual circumstances.
8630630 A review of the clinical pharmacokinetics of meloxicam. 1996 Apr Meloxicam is a new preferential cyclooxygenase-2 (COX-2) inhibitor currently for the treatment of osteoarthritis and rheumatoid arthritis. Its pharmacokinetic profile is characterized by a prolonged and almost complete absorption and the drug is > 99.5% bound to plasma proteins. Meloxicam is metabolized to four biologically inactive main metabolites, which are excreted in both urine and faeces. The elimination half-life (t1/2) of meloxicam is approximately 20 h. This is reflected in a total plasma clearance (CL) of 0.42-0.48 1/h. Steady-state plasma concentrations are achieved within 3-5 days. The pharmacokinetic parameters of meloxicam are linear over the dose range 7.5-30 mg and bioequivalence has been shown for a number of different formulations. No interactions were observed following the concomitant administration of food, cimetidine, antacid, aspirin, beta-acetyldigoxin, methotrexate, warfarin or furosemide. Neither hepatic insufficiency nor moderate renal dysfunction have any relevant effects on the pharmacokinetics of meloxicam and dosage adjustments in the elderly are not required.
7789287 Controversies in selection of epoetin dosages. Issues and answers. 1995 Apr Epoetin (recombinant human erythropoietin) is now a widely available though expensive treatment for the anaemia of chronic renal failure, and is effective in more than 95% of patients. Complications of epoetin in this context include hypertension in a third of cases, including hypertensive encephalopathy in a few, and thrombosis of shunts or vascular access devices. Fears that epoetin would cause progression of renal failure have not generally been confirmed, but hyperkalaemia may be a problem in the initial phase of treatment. Epoetin is up to twice as effective when administered subcutaneously rather than intravenously. Responding patients will normally do so within 3 months of starting epoetin. Failures to respond are usually due to iron deficiency or intercurrent disease. Other diseases associated with anaemia and an inappropriately low serum epoetin level include prematurity, the anaemia of cancer and rheumatoid arthritis. The baseline serum endogenous erythropoietin may provide a guide to response in some of these cases. Some encouraging results are being published. Situations where the serum erythropoietin levels are normal or elevated where epoetin has been employed include boosting of haematocrit presurgery as an adjunct to autologous blood donation, treatment of anaemic patients with myelodysplastic syndromes, and improvement of athletic performances.
7875307 The non-steroidal anti-inflammatory drug, indomethacin, as an inhibitor of HIV replication 1995 Feb 20 Indomethacin, a common non-steroidal anti-inflammatory drug (NSAID), has been used to treat rheumatoid arthritis. Although indomethacin has also been used as an immunopotentiator and symptomatic NSAID in AIDS, its effect on HIV replication is unknown. MT-4 lymphocytes were inoculated with HIV in the presence of indomethacin and tested for p24 expression by ELISA. The 50% inhibition (IC50) was 10 microM, corresponding to plasma levels after administration of 50 mg oral indomethacin. The antiviral effect appears to be specific since no toxicity has been observed at the IC50 dose, and unrelated NSAIDs have not shown the activity at clinical doses. Indomethacin may, thus, represent a new class of anti-HIV drug.
8545552 [Heat shock proteins in diabetes mellitus]. 1995 Jan The Heat Shock Proteins (HSP) are a special category of proteins synthesized from 2 types of cells, one originating from ordinary organs and the other highly specialized ones from mammals. Their synthesis originates from a reaction of the cells to heat shock and therefore it can be thought of as a defense mechanism activated by the cells to protect themselves from the damage done by heat. HSPs are also qualified as "molecular chaperons" since they are present at the assembling of other proteins and they protect them from any possible anomalous interactions even if they do not take an active part in the final making up of the protein itself. This chaperone role is the base of the hypothesis that HSPs could take part in the processing and presentation of the antigens. Two hypothesis have been formed on the role of HSPs in the immunological process. 1) HSP could be antigens that call for an immediate immunological reaction; 2) HSP could set off a self destructive mechanism brought on by an immunological reaction. From all this it emerges that the immunological reaction to HSP has two angles. One is protective in that it allows the cells to eliminate micro foreign-organisms and the other is harmful due to a badly regulated immunological reaction. In some studies it has been demonstrated that patients with varying autoimmunological disorders as LES and rheumatoid arthritis (AR), have autoantibodies against HSPs. Moreover the HSPs of certain microorganisms induce the formation of autoantibodies in the host and the proliferation of T cells in the synovial fluid in patients with AR.(ABSTRACT TRUNCATED AT 250 WORDS)
7638786 [Interstitial lung diseases--the clinical aspects of the problem]. 1995 Upon analysis of 550 cases of different chronic diffuse pulmonary diseases included in a group of interstitial diseases of the lungs (IDL) the authors came to the conclusion that IDL incorporate such variants as alveolitis, pulmonary vasculitis and pulmonary hemorrhages; granulomatosis covers exogenic allergic alveolitis, alveolitis in chronic active hepatitis; vasculitis group includes such rare diseases as necrotizing sarcoid granulomatosis vasculitis and lymphoid granulomatosis; fibrosing alveolitis--secondary alveolitis in sclerodermia systematica, rheumatoid arthritis, Sjogren's disease, chronic active hepatitis. Knowledge of IDL etiology (environmental, occupational, induced by radionuclides, drugs, viruses, fungi) with focus on drug affection of the lungs is thought of value. Biopsy and bronchial lavage findings are compared clinically and morphologically. Mechanisms of pulmonary fibrosis and approaches to inhibition of pulmonary fibrosis progression are outlined.
7612226 Neuroendocrine-immune system interactions and autoimmunity. 1995 The concept of an integrated bidirectionally regulated neuroendocrine-immune adaptive response to stress has strong experimental support. The quality and intensity of this coordinated response to stress varies depending upon age, gender, reproductive status, and other genetically determined factors as well as the types and magnitudes of environmental challenges. These factors and dysfunctional communication between the nervous, endocrine, and immune systems appear to contribute to the development of autoimmune diseases in the Lewis and BB rats, the OS chicken, and the NOD, MRL, NZB, NZW, and NZB/NZW F1 mice. Neuroendocrine-immune dysfunction also contributes to the pathogenesis of human autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, thyroid diseases, and others. This review highlights these concepts. It includes discussions on various aspects of the stress response, the hypothalamic-pituitary-adrenal and -gonadal axes, corticotropin releasing hormone, luteinizing hormone releasing hormone, interleukin-1 and -6, corticosteroids, estrogens, testosterone, dehydroepiandrosterone, growth hormone, prolactin, and thyroid hormone. The role of the nervous and endocrine systems in regulating thymopoiesis and T cell development is also emphasized.
7952645 The role of neutrophil elastase in chronic inflammation. 1994 Dec Passively released or actively secreted elastase from neutrophils has been linked to the pathologic processes of a variety of inflammatory diseases, including idiopathic pulmonary fibrosis, rheumatoid arthritis, adult respiratory distress syndrome, and cystic fibrosis. The serine proteinase has a broad substrate specificity and may attack a number of host proteins outside of the neutrophil, including lung elastin and fibronectin. Such a proteolysis may change the normal surrounding tissue and the protein pattern of an inflammatory focus. Additionally, it acts as a potent secretagogue in minute amounts. The reason that neutrophil elastase is present in considerable concentrations outside of the neutrophil during chronic inflammation and that the major endogenous serine proteinase inhibitor for neutrophil elastase, alpha 1-proteinase inhibitor, is easily inactivated by proteolytic and oxidative attack is unclear. Released neutrophil elastase may also be involved in regulating chronic inflammation. In a feedback mechanism, neutrophil elastase inhibits neutrophil stimulation and concomitant elastase release by cleavage of immunoglobulins, complement components, and complement receptor type 1 on neutrophils. Besides a number of harmful effects of neutrophil elastase in inflammation, the latter mechanism, although considerably impairing phagocytosis, may be beneficial particularly in the light of persistent bacterial pathogens in the human lung affected by cystic fibrosis.
8090947 The effect of psychological stress on neutrophil superoxide release. 1994 Oct Stress has long been suggested to exacerbate symptom expression in people with chronic inflammatory disorders. The release of oxidative metabolites from activated PMN plays a significant role in the pathophysiology of inflammation. Thus, we examined the effects of psychological stress on release of superoxide anions from PMN of rats with or without an inflammation induced by injection of shellfish glycogen (SFG). Psychological stress was found to significantly increase PMN superoxide release in both healthy and SFG-injected animals. Total amounts of superoxide release were similar between the two groups, suggesting that PMN from animals with a mild inflammatory condition were not more susceptible to the effects of stress than PMN from healthy animals. However, this study should be repeated using an animal model of chronic inflammation, such as airway hyperactivity or rheumatoid arthritis.
8089290 Autoimmune connective tissue disease and connective tissue disease-like illnesses after si 1994 Oct Since first reported in 1982, published anecdotal reports have appeared with increasing frequency of patients in whom autoimmune connective tissue diseases developed after mammary augmentation with silicone gel-filled elastomer envelope-type prostheses. Although scleroderma has been reported most often, other diagnoses have included systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, and mixed connective tissue disease. Other patients have ill-defined connective tissue-like illnesses often referred to as "human adjuvant disease." The occurrence of dermatomyositis and polymyositis after silicone breast implants appears to be infrequent. We report two new cases of dermatomyositis after silicone exposure. In addition, a comprehensive review of the literature pertaining to rheumatic disease and silicone gel augmentation mammoplasty is presented to provide some perspective on this highly complicated and controversial subject.
8020864 [Inhibitory effects of cytokines on human osteoblastic cells]. 1994 May We examined the effect of tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta) and IL-6 on alkaline phosphatase (ALP) and osteocalcin (OC) production, calcification and calcium (Ca) release in human cultured osteoblastic cells established from human periosteum. The cells were cultured with varying concentrations of cytokines for three days. TNF-alpha and IL-1 beta significantly inhibited ALP production, decreased cellular Ca content, and significantly enhanced 45Ca release in human osteoblastic cells. IL-6, on the other hand, significantly suppressed 45Ca release from the osteoblastic cells. Any one of these cytokines did not influence the production of OC by the osteoblastic cells. The results obtained suggest that TNF-alpha and IL-1 beta may inhibit bone formation and calcification and promote bone resorption, while the effects of IL-6 on osteoblastic cells may be a little different from those of TNF-alpha or IL-1 beta. Cytokine-dependent these effects on the osteoblastic cells may be one of the mechanisms by which bone loss occurs in patients with rheumatoid arthritis.