Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 12515972 | [The usefulness of the quantitative ultrasound to diagnose glucocorticoids induced osteopo | 2002 Dec | BACKGROUND: The aim of this study was to evaluate the utilization of heel ultrasonometry in the diagnosis of glucocorticoid induced osteoporosis. METHODS: The study group included 108 caucasian women, ranging in age from 30 to 81 years. They were all affected by inflammatory disorders (rheumatoid arthritis and other connective tissue diseases) and had been in chronic glucocorticoid therapy for at least 8 months, at an average daily dosage of not less than 7.5 mg of prednisolone. The control group was composed of 112 women. Every subject was evaluated by a heel ultrasonography (Hologic Sahara). RESULTS: The ultrasonometry data average values noted were: QUI (Quantitative Ultrasound Index) 71* (86); SOS (Speed of Sound) 1324 m/sec* (1541); BUA (Broadband Ultrasound Attenuation) 61 dB/MHz (62). The asterisk shows a statistically significant difference in comparison to the value in brackets. QUI/Stiffness and SOS had reached a significant statistic value in all the age groups, with regard to average values of patients not on glucocorticoid therapy. The BUA values did not demonstrate a significant difference, even if they always appeared inferior to the average observed (except in the range 60-70 years age group). CONCLUSIONS: The concept that osteoporosis is a disease characterized exclusively to a reduction in bone density, now leaves room for consideration that corresponds with the concepts of quantitative and quality elements. Chronic glucocorticoid therapy is one of the major causes of osteoporosis. The use of glucocorticoids increases the risk of fractures, independently from the bone ùineral BMD in the various ages, which therefore cannot be explained solely by the reduced BMD. Ultrasound may provide information on the bone structure, and so its eventual modification, after chronic glucocorticoid therapy. Our results show that bone ultrasonometry is able to detect a population in chronic glucocorticoid therapy in comparison with those not treated. BUA and SOS are reduced in all the patients. Our experience derives that in the chronic glucocorticoid therapy patients, a major prevalence is noted of SOS which may provide information on the modification of the bone structure. | |
| 14728890 | [Clinical characteristics of children with enthesitis related arthritis]. | 2003 Nov | OBJECTIVE: To study clinical characteristics of children with enthesitis related arthritis (ERA). METHODS: Twelve patients fulfilling the international league of associations for rheumatology (ILAR) criteria for classification of juvenile idiopathic arthritis (JIA) and ERA were referred to our department between August and November, 2002. Their gender, age, family history, clinical manifestations, imaging data, laboratory data and treatment regimens were analyzed retrospectively. RESULTS: Of the 12 patients, 11 were male, only one was female; their age ranged from 4 to 16 years, and the median age was 10.5 years. Ten (83%) of the patients were older than eight years. Among their first degree relatives, one had definite ankylosing spondylitis (AS), and 3 presented with a history of inflammatory low back pain. Enthesitis occurred in 9. Synovitis occurred in 11, most of which were oligoarthritis, predominantly affecting large joints of the lower limbs in an asymmetric pattern. Seven patients underwent CT scan, and only one had erosions of the sacroiliac joints to achieve a diagnosis of juvenile AS. Ten had fever at the onset, and one had a history of diarrhea preceding the symptoms of arthritis. Urethritis and balanitis circinata occurred in 3 cases fulfilling the classification criteria of Reiter's syndrome, with conjunctivitis in 2 and corneitis in one. Elevated inflammatory indicators such as white blood cell, neutrophil, platelet, erythrocyte sedimentation rate, C-reactive protein, immunoglobulins and serum complement C3 were common during the acute illness. Mild anemia was found in 4, and reactive hemophagocytosis in 4 bone marrow specimens. DNA of human parvovirus B19 was detected in sera of 2 cases. One had positive IgM antibody to coxsackie virus B. All 12 cases were rheumatoid factor negative and HLA-B27 positive. Nonsteroidal anti-inflammatory drugs and sulfasalazine were the mainstay of treatment. Corticosteroids were added in 3 cases as a "bridge" therapy due to the severe systemic inflammation. Methotrexate was used in 4 cases with refractory disease or with the hip involved, and in 2 of them cyclophosphamide was added. CONCLUSION: The clinical characteristics of ERA can facilitate an early diagnosis so as to avoid joint damage and disabilities. | |
| 15577740 | Macrophage migration inhibitory factor and its role in autoimmune diseases. | 2004 Nov | After several decades of research into the macrophage migration inhibitory factor (MIF), its diverse actions in the immune system are yet to be fully revealed. What has become clear is that MIF plays an important role in both innate and adaptive immunity. However, while several pathways mediating the function of MIF in the immune system have been established, its role in pathogenic states such as autoimmune diseases has remained unresolved. MIF has been implicated in different autoimmune diseases, including rheumatoid arthritis, glomerulonephritis, and multiple sclerosis, but knowledge about the underlying cellular and molecular mechanisms is just emerging. However, overall it appears that the inhibition of its proinflammatory action is likely to be a successful new therapeutic strategy for some autoimmune diseases, possibly by reducing the need for steroids. As more aspects of the role of this cytokine in the pathogenesis of autoimmune diseases are elucidated, better strategies to target it therapeutically can be expected. | |
| 15553044 | [Methotrexate-induced interstitial pneumonitis in a child with acute lymphoblastic leukemi | 2004 Oct | We report a case of 5-year-old boy with acute lymphoblastic leukemia who developed interstitial pneumonitis induced by methotrexate (MTX). The patient was hospitalized with fever, cough, dyspnea and hypoxemia during maintenance treatment with low dose MTX and 6-mercaptopurine. A diagnosis of MTX pneumonitis was made based on the clinical findings, viral and serologic studies, negative microbiology and the radiological features. The patient recovered after cessation of the MTX treatment. Interstitial pneumonitis caused by MTX is well-recognized and the prevalence has been estimated to be 0.3-7.5% among patients with adult rheumatoid arthritis. However, there are few reports in the literature regarding this adverse effect in patients with leukemia. Furthermore, very few cases of childhood leukemia have been reported regarding MTX induced interstitial pneumonitis. Physicians should be aware of this rare complication during maintenance treatment with weekly low dose MTX for acute lymphoblastic leukemia in children. | |
| 15088696 | Semecarpus anacardium L, nuts inhibit lipopolysaccharide induced NO production in rat macr | 2004 Apr | Traditionally S. anacardium is used for rejuvenation, rheumatoid arthritis, fever and neurological disorders. In the present study it was observed that a fraction of S. anacacrdium at dose of 1 mg/100 g body wt, significantly reduced serum cholesterol from 378.87 mg/dl in the rats fed with atherogenic diet (AD) to 197.99 mg/dl (45-52%) in the rats fed with AD diet and increased serum HDL-cholesterol (33-37%). The same fraction also inhibited LPS induced NO production in the culture activated rat peritoneal macrophages in the dose dependent manner with IC50 value at 50 ng/ml of the culture medium. The drug in the above doses was completely safe and non-toxic, (no change in the enzymes), to liver and kidney functions. | |
| 15037488 | Clinical considerations in premenopausal osteoporosis. | 2004 Mar 22 | Osteoporosis can occur at any age. In premenopausal osteoporosis, full achievement of peak bone mass may be curtailed, and accelerated bone loss may occur in young adulthood. Premenopausal osteoporosis may be associated with chronic glucocorticoid therapy, prolonged amenorrhea, anorexia nervosa, rheumatoid arthritis, and diseases that affect calcium and vitamin D metabolism. Lesser degrees of bone loss may be associated with common conditions such as dieting, low calcium intake, smoking, and oligomenorrhea. Owing to a paucity of prospective studies on screening and treatment in younger age groups, few practice recommendations exist to guide the management of osteoporosis in young adults. We review the most important clinical concerns in premenopausal osteoporosis, including measurement of bone mass, normal bone accrual, risk factors for premature bone loss, clinical outcomes, and management issues. We emphasize clinically relevant information for primary care physicians, who are usually the first to encounter premenopausal patients with risk factors for early bone loss. | |
| 14633091 | Acute eosinophilic pneumonia associated with intravesical bacillus Calmette-Guérin therap | 2003 Nov | A 71-year-old man with a history of rheumatoid arthritis was treated with intravesical bacillus Calmette-Guérin (BCG) instillation of 80 mg once-a-week for carcinoma in situ. He developed low-grade fever followed by dyspnea and severe hypoxemia. Radiological and laboratory studies revealed bilateral diffuse reticulonodular infiltrates and hypereosinophilia. A lymphocyte stimulation test for BCG was strongly positive. From these findings, a pulmonary hypersensitivity reaction to immunotherapy was suspected, and therefore, methylprednisolone (500 mg per day) was started. After that, the fever and dyspnea disappeared, the hypereosinophilia was normalised and chest radiography results were clear. The present case is the first reported case of eosinophilic pneumonia following intravesical BCG therapy. | |
| 14561158 | Mechanisms leading to autoantibody production: link between inflammation and autoimmunity. | 2003 Sep | Several lines of evidence have suggested that autoreactive antibodies (Abs) may be triggered by some endogenous antigen (Ag) and undergo affinity maturation toward the target through somatic mutation coupled with isotype switching. To understand the mechanism leading to pathogenic auto-Ab production, it is of great importance to analyze endogenous Ags that can break immunologic tolerance and reveal how the triggered auto-Abs evolve to acquire pathogenicity. As for the first issue, chemically modified self-proteins that are frequently found in inflamed tissues are potential candidates. These post-translational modifications might give rise to the generation of neoepitopes to which T- and B- lymphocytes are not tolerated. In the second part, it is discussed how auto-Abs thus triggered undergo affinity maturation toward target auto-Ags. Recently, not only immature B cells in the bone marrow, but also a population of peripheral B cells have been shown to undergo secondary V(D)J recombination of immunoglobulin genes, thereby changing the Ag-specificity. This process is termed receptor revision, which, along with somatic mutation, is considered to contribute to the formation of high-affinity Abs. Receptor revision and somatic mutation may generate auto-Abs if the deletion mechanism of autoreactive clones is impaired. B cells that had undergone receptor revision have been isolated from ectopic germinal centers in inflamed tissues in patients with rheumatoid arthritis. Investigations on the link between inflammation and autoimmunity will provide new aspects for therapeutic targets in the treatment of autoimmune diseases. | |
| 12876670 | Survival signals in leukemic large granular lymphocytes. | 2003 Jul | The central hypothesis of our laboratory research program in large granular lymphocyte (LGL) leukemia is that leukemic LGL represent antigen-driven cytotoxic T lymphocytes (CTL) with characteristics of dysregulated apoptosis. The clinical features of LGL leukemia highlight the association of autoimmune diseases such as rheumatoid arthritis with the T-cell form of LGL leukemia. We therefore used LGL leukemia as a model disease of dysregulated apoptosis leading to both malignant and autoimmune diseases. Here, we review our understanding of survival signals activated in leukemic LGL in the context of knowledge concerning apoptotic pathways in activated normal lymphocytes. | |
| 12776964 | Diagnostic and therapeutic injection of the hip and knee. | 2003 May 15 | Joint injection of the hip and knee regions is a useful diagnostic and therapeutic tool for the family physician. In this article, the injection procedure for the greater trochanteric bursa, the knee joint, the pes anserine bursa, the iliotibial band, and the prepatellar bursa is reviewed. Indications for greater trochanteric bursa injection include acute and chronic inflammation associated with osteoarthritis, rheumatoid arthritis, repetitive use, and other traumatic injuries to the area. For the knee joint, aspiration may be performed to aid in the diagnosis of an unexplained effusion and relieve discomfort caused by an effusion. Injection of the knee can be performed for viscosupplementation or corticosteroid therapy. Indications for corticosteroid injection include advanced osteoarthritis and other inflammatory arthritides, such as gout or calcium pyrophosphate deposition disease. Swelling and tenderness of pes anserine or prepatellar bursae can be relieved with aspiration and corticosteroid injection. Persistent pain and disability from iliotibial band syndrome respond to local injection therapy. The proper technique, choice and quantity of pharmaceuticals, and appropriate follow-up are essential for effective outcomes. | |
| 12775892 | Human single-chain Fv (scFv) antibody specific to human IL-6 with the inhibitory activity | 2002 | Human anti-IL-6 antibody may be useful for the immunotherapy of various inflammatory diseases, such as rheumatoid arthritis. Since IL-6 is a growth factor for B cell hybridoma, it is not easy to isolate murine B cell hybridomas producing the anti-IL-6 antibody with the IL-6-signaling inhibitory activity. In this study, the antibody library (Vgamma-Vkappa, Vgamma-Vlambda, Vmu-Vkappa or micro-Vlambda ligated into the pCANTAB 5E phagemid vector) was prepared from peripheral blood mononuclear cells of 20 healthy subjects. The phage display library was panned with an IL-6-coated plastic plate, and the binding specificity was confirmed by ELISA and BIAcore. From the antibody library (Vgamma-Vlambda), five IL-6-specific phage clones were isolated. The effects of the soluble scFvs purified from these phage clones were tested on the growth of the IL-6-dependent human cell line, KT-3. Two of these clones significantly inhibited the growth of KT-3, and three showed no inhibition. | |
| 12440965 | Tailoring anti-complement therapeutics. | 2002 Nov | Complement is a core component of the immune system, which performs vital roles in immune surveillance. However, the active products that enable complement to perform its physiological roles can inappropriately target self tissues and cause pathology. Complement-mediated inflammation and tissue destruction is an important drive to pathology in diseases as diverse as rheumatoid arthritis and dementia. Two decades ago there were no agents that could be used therapeutically to inhibit the activation of complement, but increased understanding of the natural control of complement in vivo has markedly changed this situation. The realization that drugs mimicking the action of the complement regulatory proteins present on self cells, and in plasma, could effectively control pathological activation of complement has opened the door to the use of anticomplement therapy in disease. Here we will review the development of anticomplement therapeutics from the first generation agents, which are unmodified recombinant forms of natural regulators, to recent strategies for making better drugs. We will describe strategies for targeting the anticomplement activity to the site of disease, and for extending the plasma half-life of the agent. Finally, we will illustrate a novel approach to the delivery of anticomplement agents, making prodrugs that are activated only at disease sites thus minimizing the deleterious effects of systemic complement inhibition. | |
| 12403347 | Inhibition of T cell responses by transferrin-coupled competitor peptides. | 2002 | Activation of helperT cell has been implicated in a number of autoimmune diseases including rheumatoid arthritis. The underlying mechanism that initiates and promotes disease progression remains unclear, but it is apparent that helper T cells and autoantigens play prominent roles. Identification of the autoantigens has proven to be extremely difficult, and therefore strategies for promoting tolerance induction remain limited. Since autoimmune diseases are closely associated with specific major histocompatibility complex class II molecules such as HLA-DR4, the use of competitor peptides is an alternative strategy. A limitation of competitor peptides, however, is that they are ineffective in vivo. In the studies presented here, we demonstrate that coupling competitor peptides to a cell-surface receptor ligand, transferrin, enhances their ability to block helper T cell responses using the DO11.10 transgenic mouse as our model system. | |
| 12325334 | [A case of secondary pulmonary cryptococcosis showing various radiographic changes during | 2002 Jun | A 58-year-old man who had been prescribed corticosteroids for rheumatoid arthritis in another hospital was admitted to our hospital for examination of an abnormal chest shadow. We obtained a positive result for cryptococcal antigen in the serum, in a measurement done as a screening test for abnormal chest shadows. We diagnosed secondary pulmonary cryptococcosis through a transbronchial biopsy. He showed various radiographic changes, including multiple nodular shadows, cavities and partial resolution during the natural course without antifungal treatment. This case taught us that secondary pulmonary cryptococcosis causes a more varied range of radiographic changes than its primary form, that measurement of cryptococcal antigen in serum is useful as a screening test of pulmonary cryptococcosis, and that it is important to consider whether a particular patient should be treated or not. | |
| 12087907 | [Incidence rate of rheumatic diseases in Russian population: 10-year analysis]. | 2002 | AIM: To analyze trends in rheumatic diseases (RD) incidence rate in population of Russia for a recent decade. MATERIAL AND METHODS: Medical RD statistics for all regions of Russia for 10 years (1990-1999) have been analysed. RESULTS: Annual number of primary patients with RD has increased for 1990-1999 from 9,147,000 to 12,378,000 (by 35.3%). The percentage of patients with acute rheumatic fever and chronic RD of the heart diminished from 6.5 to 2.9%. Most of the diseases constitute the diseases of osteomuscular system and connective tissue (DOMS). The number of new cases with rheumatic heart diseases (RHD) in adolescents and adults has risen by 50 and 40%, respectively. RHD are especially frequent in the Volga-Vyatka and North-Caucasian regions (2.5 and 2.3 per 1000 against mean Russian 1.7). A total DOMS morbidity has increased for the recent decade by 41%. It is higher in the Central and North regions, in the West Siberia and lower in the North Caucasus, Far East, East Siberia. For the 7 years the above morbidity among children rose 2-fold, among adolescents--2.4-fold. Incidence of rheumatoid arthritis and ankylosing spondylarthritis in adult population of Russia has changed insignificantly while osteoarthrosis total and primary occurrence for 6 years increased by 78 and 58%, respectively. CONCLUSION: RD become a real challenge for health service of Russia. Changes in RD structure require correction of the rheumatic service activities. | |
| 12052220 | Macrophage migration inhibitory factor and the discovery of tautomerase inhibitors. | 2002 | Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine released from T-cells and macrophages, and is a key molecule in inflammation. Although a detailed understanding of the biological functions of MIF has not yet been found, it is known that MIF catalyzes the tautomerization of phenylpyruvate and a non-physiological molecule, D-dopachrome. A potent tautomerase inhibitor would be expected, as a validation tool, to shed light on role of MIF activity and the relationship between its biological and enzymatic activity. Such tautomerase inhibitors would be useful in the treatment of MIF-related diseases, such as sepsis, acute respiratory distress syndrome (ARDS), asthma, atopic dermatitis, rheumatoid arthritis (RA), nephropathy and tumors. In this review, we have focused on (1) the biological and enzymatic activities of MIF, (2) the discovery of novel, drug-like tautomerase inhibitors of MIF using a structure-based computer-assisted search, and (3) a crystallographic and molecular modeling study of the MIF-tautomerase inhibitor complexes (A review with 133 references). | |
| 11957195 | Chronic neutropenia associated with autoimmune disease. | 2002 Apr | Chronic neutropenia with autoimmune diseases is associated mainly with rheumatoid arthritis (RA), as Felty's syndrome or large granular lymphocyte (LGL) leukemia, and with systemic lupus erythematosus (SLE). Recent advances have allowed better understanding regarding the mechanism of neutropenia and improved options for treatment. Target antigens for antineutrophil antibodies have been identified for both Felty's syndrome and for SLE. The role of soluble Fas-ligand (FasL) in inducing apoptosis of neutrophils has been clarified for LGL leukemia and increased neutrophil apoptosis has been described in neutropenic patients with SLE. The role of immune complexes in affecting neutrophil traffic and function continues to be studied. Treatments of neutropenia have included methotrexate, cyclosporine A, and granulocyte colony-stimulating factor (G-CSF) as well as granulocyte-macrophage colony-stimulating factor (GM-CSF). The efficacy of both GM- and G-CSF in reversing neutropenia and decreasing the risk of infections in Felty's syndrome and SLE has been well documented. Of concern, however, have been flares of symptoms or development of leukocytoclastic vasculitis in some patients following the use of these cytokines. Recent results suggest that in these patients G-CSF should be administered at the lowest dose effective at elevating the neutrophil count above 1,000/microL. | |
| 11861058 | Safety of implantable contraceptives for women: data from observational studies. | 2002 Jan | Contraceptive implants are registered in over 60 countries and have been used by millions of women for three decades. This article reviews findings from observational studies on the safety of contraceptive implants and examines the risk of specific health outcomes. Fifty-five articles were reviewed, and the body of evidence for each health outcome was summarized. Available evidence suggests that contraceptive implants are safe and, overall, implant users do not experience adverse events at rates higher than women not using implants. With respect to specific outcomes, the evidence suggests no increased risks of pelvic inflammatory disease, decreased bone mineral density, anemia, thrombocytopenia, or death with implant use. The evidence was too limited to draw meaningful conclusions for neoplastic disease, cardiovascular events, and HIV/AIDS. Nonsignificantly elevated associations were reported for diabetes, serious mental disorders, and rheumatoid arthritis. Conditions for which risks were marginally, yet significantly, elevated were hypertension and gall bladder disease. | |
| 11856830 | Structure of a Cys25-->Ser mutant of human cathepsin S. | 2002 Mar | Cathepsin S (EC 3.4.22.27), a cysteine proteinase of the papain superfamily, plays a critical role in the generation of a major histocompatibility complex (MHC) class II restricted T-cell response by antigen-presenting cells. Therefore, selective inhibition of this enzyme may be useful in modulating class II restricted T-cell responses in immune-related disorders such as rheumatoid arthritis, multiple sclerosis and extrinsic asthma. The three-dimensional structure at 2.2 A resolution of the active-site Cys25-->Ser mutant presented here in an unliganded state provides further insight useful for the design of selective enzyme inhibitors. | |
| 15525299 | Associated conditions in myasthenia gravis: response to thymectomy. | 2004 Nov | To compare the response of thymectomy in patients with associated conditions (PWAC) and without associated conditions (PWOAC). Comparative, retrospective. 198 patients with the established diagnosis of myasthenia gravis who had a thymectomy between 1987 and 2000, and who were folowed up for at least 3 years. We formed two groups, one with associated conditions and the second without associated conditions. The patients were divided into four groups: (i) patients in remission, (ii) patients with improvement, (iii) patients without changes, and (iv) patients whose condition worsened. Associated conditions (AC) were found in 49 patients (26%). The main associated conditions were hyperthyroidism in 16 patients (33%) hypothyroidism in seven (14%), rheumatoid arthritis in five (10%) and hypothyroidism and Sjogren syndrome in three (6%). Concerning the response of thymectomy, 13 patients WAC showed remission (27%), vs. 54 patients WOAC (39%). Twenty patients WAC showed improvement (41%) vs. 46 WOAC (33%). Thirteen patients WAC had no changes (27%) vs. 37 WOAC (26%). Finally, in three patients WAC their condition worsened (6%) vs. three WOAC (2%). The response to thymectomy was high (69%) in both groups. We did not identify significant differences. |