Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 9140093 | Depletion of T lymphocytes with immunotoxin retards the progress of experimental allergic | 1997 Apr 10 | FN18-CRM9 is an anti-rhesus anti-CD3 immunotoxin that can transiently deplete T cells to 1% of initial values in both the blood and lymph node compartments and can induce long-term tolerance to mismatched renal allografts. We have investigated the ability of this immunotoxin to interdict the course of an experimental rhesus T-cell-driven autoimmune disease, experimental allergic encephalomyelitis (EAE) induced by myelin basic protein. Monkeys showing CSF pleocytosis were then treated with FN18-CRM9 alone or in combination with cranial irradiation (325 or 650 cGy). EAE in nontreated control monkeys progressed rapidly. Paralysis occurred 4-6 days after CSF pleocytosis. Paralysis was either delayed or never occurred in treated monkeys, and histopathology revealed few inflammatory plaques that were notable for their low or absent T cell content. While T cells repopulate in the periphery posttreatment, they do not return to the CNS in large numbers, suggesting that the newly repopulated T cells have lost their previously acquired CNS homing capability. Anti-CD3 immunotoxin may be useful in treating clinical T-cell-driven autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. | |
| 9212672 | [Bilateral hilar and mediastinal lymphadenopathy accomporying pulmonary infiltration with | 1997 Apr | A 46-year-old man had had an occasional dry cough in the early morning since about the age of 20, but had received no treatment. He had been taking an antirheumatic drug for 2 years for rheumatoid arthritis. The patient complained of fever and dry coughing that began in the middle of November 1995, and he was treated for acute bronchitis. His condition did not improve, and he was admitted to the hospital in early December. Wheezing and rhonchi were heard in both lung fields. His white blood cell count was 19,000/mm3, and the eosinophil percent age was 48%. A chest CT scan revealed macular lesions with an increased density in both lung fields, and markedly swollen mediastinal and hilar lymph nodes. Analysis of alveolar lavage fluid revealed an increased number of cells (total) and eosinophilia (37%), and examination of a transbronchial lung biopsy specimen indicated infiltration with eosinophils and lymphocytes. Our diagnosis was eosinophilic pneumonia. The patient's condition improved soon after the start of pulse therapy with steroids. Bilateral swelling of mediastinal and hilar lymph nodes is rare in patients who have pulmonary in filtration with eosinophilia (the PIE syndrome). | |
| 12825458 | Mechanisms for modulating TNF alpha in immune and inflammatory disease. | 2001 Sep | The development of tumor necrosis factor-alpha (TNF alpha) inhibitors has been one of the most active areas of drug development over the last ten years for the treatment of inflammatory diseases. Following the definition of TNF alpha as a key mediator of inflammatory disease and the success demonstrated by various anti-TNF alpha strategies in the treatment of rheumatoid arthritis and inflammatory bowel disease, many investigators have sought to refine mechanisms by which to modulate TNF alpha in vivo. Many advances are presently being made in the understanding of how TNF alpha production is regulated, and with this knowledge comes the identification of new targets and pathways for therapeutic intervention. Here, we review the development of the currently available therapeutics and the progressive steps that are being made to improve clinical efficacy of anti-TNF alpha strategies. | |
| 12805765 | Breaking immunological tolerance through OX40 (CD134). | 2001 Nov 6 | Immunological tolerance represents a mechanism by which cells of the host remain protected from the immune system. Breaking of immunological tolerance can result in a variety of autoimmune diseases such as rheumatoid arthritis, diabetes, and multiple sclerosis. The reasons for tolerance breaking down and autoimmune processes arising are largely unknown but of obvious interest for therapeutic intervention of these diseases. Although reversal of the tolerant state is generally unwanted, there are instances where this may be of benefit to the host. In particular, one way a cancerous cell escapes being targeted by the immune system is through tolerance mechanisms that in effect turn off the reactivity of T lymphocytes that can respond to tumor-associated peptides. Thus tolerance represents a major obstacle in developing effective immunotherapy against tumors. The molecules that are involved in regulating immunological tolerance are then of interest as they may be great targets for positively or negatively manipulating the tolerance process. | |
| 11846338 | Bisphosphonates for the prevention and treatment of corticosteroid-induced osteoporosis. | 2001 Dec | Corticosteroid-induced osteoporosis is a common occurrence among several different patient populations, including individuals undergoing therapy for rheumatoid arthritis, temporal arteritis, polymyalgia rheumatica, chronic lung disease, asthma and organ transplantation. The clinical trial data reviewed here demonstrate that bisphosphonate therapy can reverse, at least in part, established corticosteroid-induced osteoporosis, increase BMD, and prevent the development of new fractures. The consistency of results, with varying treatment regimens and in slightly different patient populations, provides strong support for the generalizability of these findings and for the use of bisphosphonates in corticosteroid-induced osteoporosis. These results are consistent with the findings from a recent meta-analysis, which reviewed data from 13 controlled clinical trials of bisphosphonate use in corticosteroid-induced osteoporosis. In that analysis, 1 year of bisphosphonate therapy produced a significant increase in BMD at the lumbar spine (average difference in BMD between treated and control groups of 4.0%) and femoral neck (average BMD difference of 2.1% between treated and control patients). Bisphosphonate therapy, therefore, appears to be an effective, well-tolerated means of reducing the risk of bone fractures among patients treated with corticosteroids. | |
| 11808999 | Treatment of spondyloarthropathies. Recent advances and prospects in 2001. | 2001 Dec | The management of patients with spondyloarthropathy is undergoing radical changes in several areas and for several reasons. The main reason seems to be improved awareness of the fairly high prevalence of this group of disorders, which is close to that of rheumatoid arthritis. Evaluation of the various treatment modalities has benefited from work by the international Assessment in Ankylosing Spondylitis group (ASAS) group aimed at developing standardized evaluation criteria. Controlled treatment trials have provided useful information on non-pharmacological treatments such as physical exercise programs and patient information. Nonsteroidal anti-inflammatory drugs (NSAIDs) remain the cornerstone of the pharmacological treatment. Recent studies have shown that NSAIDs capable of selectively inhibiting type 2 cyclooxygenase have a better gastrointestinal safety profile and are as effective in relieving clinical symptoms as conventional NSAIDs. Importantly, maintenance treatment seems effective not only on peripheral joint manifestations but also on axial manifestations that fail to respond to NSAIDs. Thalidomide and TNF antagonists are promising maintenance agents. | |
| 11606034 | Interactions of aspirin and salicylic acid with prednisolone for inhibition of lymphocyte | 2001 Oct | The anti-inflammatory properties of salicylates and prednisolone were investigated using inhibition of in vitro phytohemagglutinin-stimulated lymphocyte proliferation in human whole blood from healthy male and female subjects. Steroids and salicylates are used in conjunction for the treatment of inflammatory disorders such as rheumatoid arthritis and inhibit the proinflammatory transcription factor, NFKB, by different mechanisms. Data generated using various combinations of these drugs were analyzed using isobolograms and the universal surface response approach based on the Loewe additivity principle. The interaction between aspirin and prednisolone was mildly antagonistic while that between salicylic acid and prednisolone was modestly synergistic at therapeutic concentrations. Further, aspirin was slightly more potent in males, but the nature of the steroid-salicylate interaction was similar across genders. This study helps rationalize part of the beneficial effects of steroids and salicylates in treatment of inflammatory disorders. | |
| 11361034 | Superantigens: the good, the bad, and the ugly. | 2001 Mar | Increasing evidence suggests that superantigens play a role in immune-mediated diseases. Superantigens are potent activators of CD4+ T cells, causing rapid and massive proliferation of cells and cytokine production. This characteristic of superantigens can be exploited in diseases where strong immunologic responses are required, such as in the B16F10 animal model of melanoma. Superantigen administration is able to significantly enhance ineffective anti-tumor immune responses, resulting in potent and long-lived protective anti-tumor immunity. However, superantigens are more well-known for the role they play in diseases. Studies using an animal model for neurologic demyelinating diseases such as multiple sclerosis show that superantigens can induce severe relapses and activate autoreactive T cells not involved in the initial bout of disease. This may also involve epitope spreading of disease. Superantigens have also been implicated in acute diseases such as food poisoning and TSS, and in chronic diseases such as psoriasis and rheumatoid arthritis. Viral superantigens are also involved in the disease process, including superantigens derived from human immunodeficiency virus and mouse mammary tumor virus. Finally, immunotherapies that ameliorate the role played by superantigens in disease are discussed. | |
| 11260928 | [Prevention of development of pulmonary tuberculosis in compromised host]. | 2001 Feb | Recently compromised hosts have increased due to aging of population, advance of medical technology and therapy or changes in the dietary life and social life. Concomitantly the proportion of compromised hosts in the patients with pulmonary tuberculosis has also increased. Taking up diabetes mellitus, hemodialysis, collagen disease and lung cancer as the representatives of compromised hosts, we studied the propriety of chemoprophylaxis to prevent the development of tuberculosis and the standard for the subjects in the case of chemoprophylaxis being given. Diabetics top the patients in the high risk group of developing pulmonary tuberculosis. Therefore, giving chemoprophylaxis is considered necessary to prevent the development of tuberculosis from diabetics. Chemoprophylaxis to diabetics should be given only when healing of tuberculosis has been found despite the history of treatment for tuberculosis being absent. In the patients of hemodialysis, the total morbidity of tuberculosis is high, but the morbidity of pulmonary tuberculosis is not too high, so chemoprophylaxis for the patients on hemodialysis is not always necessary. However, chemoprophylaxis according to the same standard for diabetics is necessary for the patients with diabetic nephropathy. In the patients with collagen disease except rheumatoid arthritis under consideration for administration of corticosteroid preparations, chemoprophylaxis is considered desirable where doses of more than 10 mg in terms of prednisolone are administered over a long period of time. In the patients with lung cancer under consideration for administration of corticosteroid preparations, chemoprophylaxis is considered desirable where doses of more than 10 mg in terms of prednisolone are administered over a long period of time. | |
| 11018564 | Identifying clinical trials in the medical literature with electronic databases: MEDLINE a | 2000 Oct | The objective of this study was to compare the performance of MEDLINE and EMBASE for the identification of articles regarding controlled clinical trials (CCTs) published in English and related to selected topics: rheumatoid arthritis (RA), osteoporosis (OP), and low back pain (LBP). MEDLINE and EMBASE were searched for literature published in 1988 and 1994. The initial selection of papers was then reviewed to confirm that the articles were about CCTs and to assess the quality of the studies. Selected journals were also hand searched to identify CCTs not retrieved by either database. Overall, 4111 different references were retrieved (2253 for RA, 978 for OP, and 880 for LBP); 3418 (83%) of the papers were in English. EMBASE retrieved 78% more references than MEDLINE (2895 versus 1625). Overall, 1217 (30%) of the papers were retrieved by both databases. Two hundred forty-three papers were about CCTs. Two-thirds of these were retrieved by both databases, and one-third by only one. An additional 16 CCTs not retrieved by either database were identified through hand searching. Taking these into account, EMBASE retrieved 16% more CCTs than MEDLINE (220 versus 188); the EMBASE search identified 85% of the CCTs compared to 73% by MEDLINE. No significant differences were observed in the mean quality scores and sample size of the CCTs missed by MEDLINE compared to those missed by EMBASE. Our findings suggest that the use of MEDLINE alone to identify CCTs is inadequate. The use of two or more databases and hand searching of selected journals are needed to perform a comprehensive search. | |
| 11005242 | Integrin activation by chemokines: relevance to inflammatory adhesion cascade during T cel | 2000 Oct | The adhesive function of integrins is regulated through cytoplasmic signaling induced by several stimuli, whose process is designated "inside-out signaling". A large number of leukocytes are rapidly recruited to the sites of inflammation where they form an essential component of the response to infection, injury, autoimmune disorders, allergy, tumor invasion, atherosclerosis and so on. The recruitment of leukocytes into tissue is regulated by a sequence of interactions between the circulating leukocytes and the endothelial cells. Leukocyte integrins play a pivotal role in leukocyte adhesion to endothelial cells. During the process, the activation of integrins by various chemoattractants, especially chemokines, is essential for integrin-mediated adhesion in which a signal transduced to the leukocyte converts the functionally inactive integrin to an active adhesive configuration. We have proposed that H-Ras-sensitive activation of phosphoinositide 3 (PI 3)-kinase and subsequent profilin-mediated actin polymerization, can be involved in chemokine-induced integrin-dependent adhesion of T cells. The present review documents the relevance of cytoplasmic signaling and cytoskeletal assembly to integrin-mediated adhesion induced by chemoattractants including chemokines during inflammatory processes. In contrast, various adhesion molecules are known to transduce extracellular information into cytoplasm, which leads to T cell activation and cytokine production from the cells, designated "outside-in signaling". Such a bi-directional "cross-talking" among adhesion molecules and cytokines is most relevant to inflammatory processes by augmenting immune cell migration from circulation into inflamed tissue such as rheumatoid arthritis, tumor invasion, Behçet's disease and atherosclerosis. | |
| 10984641 | Brain matrix metalloproteinase 1 levels are elevated in Alzheimer's disease. | 2000 Sep 22 | Several lines of evidence indicate that there may be an inflammatory component to the pathology of Alzheimer's disease (AD), the major form of degenerative dementia in the elderly. Activity of inflammatory cells, and the elaboration of toxic molecules by such cells may be a significant factor in disease progression. In peripheral inflammatory states, the increased activity of matrix metalloproteinase (MMP) enzymes are a major cause of tissue breakdown and secondary damage in diseases such as rheumatoid arthritis. The activity of such enzymes in the normal or diseased central nervous system is, however, not well characterized. We have therefore determined the levels of MMP 1 (collagenase) in the normal human brain and in AD. MMP1 levels were relatively low though were significantly elevated by approximately 50% in AD in all cortical areas examined. Given the activity towards collagen of MMP1, it is possible that enhanced MMP1 activity in AD, may contribute to the blood-brain barrier dysfunction seen in AD. | |
| 10678085 | Systemic anti-inflammation by synthetic interleukin-1 blockers. | 1999 May | AIM: To study the systemic anti-inflammatory actions of interleukin-1 (IL-1) blockers, OB-101 and OB-186. METHODS: Prevention of palm swelling induced by carrageenin injection was used as an animal model of systemic anti-inflammation efficacy. RESULTS: Both OB-101 and OB-186 (10-30 mg.kg-1) were approximately 10-30-fold more potent than aspirin (300 mg.kg-1) to inhibit carrageenin-induced systemic inflammation. The LD50 of OB-101 and OB-186 were at least 20 g.kg-1 i.g., indicating that they were extremely safe agents with a therapeutic index (LD50/ED50) of at least 2000. CONCLUSION: These IL-1 blockers are extremely safe systemically and are useable for the treatment of systemic inflammation such as rheumatoid arthritis. | |
| 10501847 | Tumor-induced immune dysfunction. | 1999 Oct | Immune system-based approaches for the treatment of malignant disease over the past decades have often focused on cytolytic effector cells such as cytotoxic T lymphocytes (CTL), and natural killer (NK) cells. It has also been demonstrated that tumor-bearing mice can be cured using a wide variety of approaches, some of which involve cytokine-mediated enhancement of CTL and NK cell activity. However, the apparent success in mice stands in contrast to the current situation in the clinic, wherein only a minority of patients have thus far benefited from CTL- or NK cell-based antitumor approaches. The underlying causes of tumor-associated immune suppression of CTL and NK cell activity are discussed, and features of interest shared with HIV infection, leprosy, and rheumatoid arthritis are also be mentioned. Remarkable and very recent observations have shed more light upon the causes of dysfunctional alterations in CTL and NK cells often associated with these diseases, that in turn have suggested new immunotherapeutic approaches for cancer and infectious disease. | |
| 10391323 | Aortic allografts and pulmonary autografts for replacement of the aortic valve and aortic | 1999 Jun | BACKGROUND: Extensive experience has accumulated with the use of aortic and pulmonary autografts for replacement of the aortic valve and the aortic root. Three general techniques for insertion have been used: subcoronary (free-hand) valve implantation, mini- or inclusion-root implantation, and aortic root replacement. Thirty-day mortality for elective operations with all of these techniques has not exceeded 5%. Thromboembolic episodes have been rare, and endocarditis has occurred infrequently. Early hemodynamic performance has been excellent, without significant gradients or valve regurgitation in the majority of patients. METHODS AND RESULTS: Progressive aortic regurgitation has been observed with continued follow-up, and is the most important complication of both types of valves. Leaflet failure and technical problems are the major causes of reoperation for patients receiving aortic allografts. There is some evidence to suggest that the prevalence of these complications is lower with the root replacement technique than with the intraaortic implantation methods. CONCLUSIONS: Reoperation for regurgitation of the neoaortic valve is the major complication of the pulmonary autograft procedure. The incidence of reoperation appears to be lowest with the root replacement technique. Certain conditions (acute rheumatic fever, juvenile rheumatoid arthritis, systemic lupus, ankylosing spondylitis, Libman-Sachs endocarditis, and possibly a dilated aortic root) may be contraindications to the use of a pulmonary autograft. Reoperation on the pulmonary allograft that is used to replace the autograft may be necessary in up to 20% of patients at 20 years. | |
| 9460610 | Sensitizing students to functional limitations in the elderly: an aging simulation. | 1998 Jan | BACKGROUND AND OBJECTIVES: Using activities of daily living (ADLs) and instrumental activities of daily living (IADLs) as a focus, faculty at Eastern Virginia Medical School provide an aging simulation exercise for a mandatory fourth-year clerkship in geriatrics. The specific aims of the simulation are to 1) experience the physical frailties of aging, 2) develop creative problem-solving techniques, 3) identify feelings regarding the experience of functional loss, and 4) develop proactive clinical approaches to the care of the elderly. METHODS: Students are assigned one of four diagnoses (Parkinson's disease, rheumatoid arthritis, advanced diabetes, or stroke) and are then impaired to simulate the frailties of the condition, using a variety of clothes, bindings, and other devices. In their "impaired states," they perform ADLs and IADLs, such as paying bills, organizing their pills, shopping, toileting, dressing, and eating. RESULTS: Evaluation results show the aging simulation to be the highest rated program in the clerkship. A pre- and post-course survey on attitudes toward the elderly showed a statistically significant improvement in students' attitudes toward the elderly following the course. CONCLUSIONS: Simulation exercises in aging are useful activities for helping students better understand the feelings and needs of the elderly. | |
| 9207942 | A new rational hypothesis for the pharmacophore of the active metabolite of leflunomide, a | 1997 Jun 20 | Leflunomide is one of the most promising disease-modifying antirheumatic drug now in clinical trials for the treatment of rheumatoid arthritis. Metabolic studies have indicated that leflunomide is rapidly processed in vivo to an active metabolite, A771726 (2). To identify the chemical characteristics necessary for the immunosuppressive activity of 2, configurational and conformational studies were carried out on the latter and its inactive analogues (ethyl 3-hydroxy-2-((4-(trifluoromethyl)phenyl)carbamoyl)but-2-enoate, 3a, and 3-hydroxy-2-nitro-N-(4-(trifluoromethyl)phenyl)but-2-enamide, 3b). These studies suggested that the pharmacophore responsible for the immunosuppressive activity of 2 is a beta-keto amide with the enolic hydroxy group cis to the amidic moiety. To verify this hypothesis, a new class of immunosuppressive agents was designed and synthesized. Their testing in vitro and in vivo identified compounds which were more potent than both leflunomide and 2 and above all confirmed our hypothesis as to the key structural and chemical determinants for the immunosuppressive properties of 2 and our compounds. | |
| 10374293 | [Systemic manifestations of myasthenia gravis and its putative pathogenesis]. | 1997 Jun | We studied the systemic manifestations of myasthenia gravis and its putative pathogenesis. 644 clinically, pharmacologically and electrophysiologically diagnosed patients with myasthenia gravis (MG) were studied. 33 patients had Graves disease, 5 periodic paralysis, 4 Hashimoto disease, and 4 epilepsy, polymyositis, rheumatoid arthritis and Guillain-Barre syndrome each. 45 patients had positive anti-skeletal-muscle antibodies, 9 positive anti-thyroid antibody, and 3 positive SSA and SSB. 11 MG patients with positive pyramidal signs (MG+PS) had no evidence of multiple sclerosis (MS) or other neurologic diseases. Compared with 12 MG patients without pyramidal signs (MG-PS) and 23 normal controls (NCs), they had not only high levels of IgGcsf and IgG syn, but also increased ratio of AChRAbcsf/AChRAbs (P < 0.05). Four MG patients had epilepsy. Four MG patients had severe memory disorders. Three MG patients had diseases of the peripheral nerves without diabetes mellitus and toxin. SGPT was significantly increased in 22 MG patients than in 9 normal controls (P < 0.05). These systemic manifestations were improved while MG was improved by immunological therapy. MG is a systemic autoimmune disease predominantly involving AChR on the postsynaptic membrane of N-M conjunction. | |
| 11437494 | Lack of detection of retroviral particles (HIAP-1) in the H9 T cell line co-cultured with | 2001 Jun | Evidence for a possible aetiopathogenetic role of endogenous and/or exogenous retroviruses (RVs) in organ- and non-organ-specific autoimmune diseases is circumstantial in both humans and animal models. Intracisternal A type particles, antigenically related to HIV, have been reported in H9 cells co-cultured with homogenates of salivary glands obtained from patients with Sjögren syndrome and with synovial fluid of patients with rheumatoid arthritis. In order to identify a possible transfer of a putative 'infective RV agent' involved in the pathogenesis of human thyroid autoimmune disease, the H9 T cell line was co-cultured not only with thyroid homogenates, but also with viable thyrocytes, both prepared from glands of patients with Graves' disease. At the end of a prolonged co-culture period (24 weeks), no RV particles could be detected by electron microscopy in the H9 cells co-cultured with both thyroid preparations. These data seem to exclude the involvement of HIAP-1 in the aetiopathogenesis of human autoimmune thyroid disease. | |
| 11339635 | Inhibition of heat-induced denaturation of albumin by nonsteroidal antiinflammatory drugs | 2001 Apr | The activity of nonsteroidal antiinflammatory drugs (NSAIDs) in rheumatoid arthritis is not only due to the inhibition of the production of prostaglandins, which can even have beneficial immunosuppressive effects in chronic inflammatory processes. Since we speculated that these drugs could also act by protecting endogenous proteins against denaturation, we evaluated their effect on heat-induced denaturation human serum albumin (HSA) in comparison with several fatty acids which are known to be potent stabilizers of this protein. By the Mizushimas assay and a recently developed HPLC assay, we observed that NSAIDs were slightly less active [EC50 to approximately 10(-5)-10(-4) M] than FA and that the HPLC method was less sensitive but more selective than the turbidimetric assay, i.e. it was capable of distinguishing true antiaggregant agents like FA and NSAIDs from substances capable of inhibiting the precipitation of denatured protein aggregates. In conclusion, this survey could be useful for the development of more effective agents in protein condensation diseases like rheumatic disorders, cataract and Alzheimers disease. |