Browse

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

ID PMID Title PublicationDate abstract
7578861 Altered development of collagen induced arthritis in T cell receptor V beta congenic B10.R 1995 Analysis of the mouse T cell receptor (TCR) V beta genome has revealed the existence of two distinct genotypes which bear deletions of certain V beta genes. Mice bearing the V beta a genotype lack approximately 50% of the V beta genome while V beta c mice lack 70% of the known V beta genes. Studies of the experimental model collagen induced arthritis (CIA) have indirectly suggested that the presence of truncated V beta genotypes may influence susceptibility to this autoimmune disease. In order to confirm the influence of V beta a and V beta c genotypes on CIA, we derived mice congenic for the known V beta haplotypes in the CIA susceptible B10.RIII (H-2r) background. Flow cytometric analysis of splenic lymphocytes revealed normal T cell levels in both B10.RIII-V beta congenic lines. Expectedly, a generalized increase in the expression of some non-deleted V beta genes was detected. In addition, the mice were immunized with porcine type II collagen and monitored for CIA. B10.RIII-V beta a mice showed little difference in arthritis incidence or severity versus B10.RIII, but a significant delay in the onset of CIA was seen. In contrast, B10.RIII-V beta c mice showed a marked decrease in arthritis incidence versus B10.RIII and the severity of CIA in arthritic mice was also significantly lower (p < 0.01). Thus, in the B10.RIII strain, the presence of truncated TCR V beta genotypes alters the development of CIA. These findings may shed light on the influence of TCR genotypes in the induction and development of human rheumatoid arthritis.
7868765 Evaluation of the Japanese-Chinese herbal medicine, kampo, for the treatment of lupus derm 1994 Dec Kampo, a Japanese-Chinese traditional herbal medicine, has been used for the treatment of various diseases for about 3,000 years in China. Among herbal medicines, Sairei-to is well known for improving the symptoms of rheumatoid arthritis (RA) and other collagen diseases. However, its immunosuppressive effects on autoimmune cutaneous phenomena are not completely understood. We investigated the effects of Sairei-to on the development of lupus dermatoses in autoimmune-prone MRL/Mp-lpr/lpr (MRL/lpr) mice, an animal model which spontaneously develops skin lesions similar to those seen in human lupus erythematosus. Virgin female MRL/lpr mice at 1 month of age, which were treated orally with Sairei-to, had reduced amounts of IgG deposition at the dermoepidermal junction, titers of anti-DNA antibodies and rheumatoid factor, and lymphoproliferation. These results support the use of traditional herbal medicines in patients with human RA and systemic lupus erythematosus.
7908879 The consequences of H2 receptor antagonist--piroxicam coadministration in patients with jo 1993 A randomised crossover study was performed in subjects with rheumatoid arthritis (or other arthropathies) to investigate if any alteration in the steady pharmacokinetics of the NSAID piroxicam (a drug which is extensively metabolised via cytochrome P450) or its major metabolites occurred as a result of coadministering either cimetidine or nizatidine. Twelve females and 2 males with mean age, weight, and albumin concentrations of 58 years, 61 kg, and 40 g.L-1 respectively, completed the study. Comparisons were made between the following parameters: plasma piroxicam AUCs [AUC0-24(P)], plasma 5-hydroxypiroxicam AUCs [AUC0-24(5-OHP)], the ratio of these i.e. AUC0-24(5-OHP):AUC0-24(p), the % piroxicam daily dose excreted in urine as 5-hydroxypiroxicam (before and after glucuronidase incubation); and the mean of the steady state trough piroxicam, and 5-hydroxypiroxicam concentrations (obtained during each study phase in addition to the wash-out period). A statistically significant difference as a result of initiating either cimetidine or nizatidine was obtained only for the ratio AUC0-23(5-OHP):AUC0-24(P). This was indicative of a weak potential to inhibit piroxicam hydroxylation. No clinically significant alteration in the steady state pharmacokinetics of piroxicam occurred in these subjects as a result of cimetidine or nizatidine coadministration. Consequently it is unlikely that any adverse events would arise from these combinations.
8872550 Orthopaedic surgery and HIV disease in Africa. 1996 Human immunodeficiency virus (HIV) infection has radically changed African orthopaedic practice within a decade. In Lusaka, a third of adults are infected, but most have no physical signs of the disease. Early experience showed that closed fractures healed normally, the risk of sepsis during osteosynthesis was increased and most open fractures became septic. Major orthopaedic surgery in HIV-positive patients has increased risks of sepsis which rise steeply in those with physical signs of HIV disease. Musculoskeletal infections such as tropical pyomyositis, adult haematogenous long-bone osteomyelitis, and late haematogenous infection of implants, appear as immune competence wanes. There is a dual epidemic of tuberculosis and HIV, and bone and joint tuberculosis is now common. Atypical features suggest that traditional diagnostic criteria for spinal tuberculosis may be inadequate. Rheumatoid diseases, especially reactive arthritis, are common and serious complications of HIV disease. The risk of transmission of HIV between patient and surgeon is small, especially if recommended precautions are universally applied.
7931088 Protective role of major histocompatibility complex class II Ebd transgene on collagen-ind 1994 Oct 1 Collagen-induced arthritis (CIA) is an animal model of autoimmune inflammatory polyarthritis that has features similar to rheumatoid arthritis (RA). Much like RA, susceptibility to mouse CIA is influenced by the major histocompatibility complex (MHC), H-2, and restricted to the H-2q and H-2r haplotypes. Whereas the role of the H-2A molecule in susceptibility to CIA is well established, little is known about the role of H-2E molecule in the disease. In this study, we analyzed the effect of a transgenic E beta d molecule on CIA susceptibility in a recombinant mouse B10.RQB3, which expresses the CIA susceptible Aq genes and an Eak gene, but does not produce an E molecule since Ebq is nonfunctional. In the presence of an Ebd transgene, a viable E molecule is generated. Whereas B10.RQB3 were susceptible to CIA, B10.RQB3-E beta d+ showed a dramatic reduction in the incidence of arthritis as well as a decrease in the level of anti-mouse and anti-bovine CII antibodies in their serum. No clear cut differences in the expression of T cell receptor (TCR) V beta was observed between E beta d+ and E beta d- transgenic mice. Mechanisms underlying the protective effect of E beta d transgenic molecule on CIA may shed light on how HLA-DR molecules influence human RA.
8882049 Studies on associations of antinuclear antibodies with antibodies to an uveitogenic peptid 1996 Feb OBJECTIVE: To determine if, in children with uveitis, antinuclear antibodies (ANA) are associated with antibodies to an uveitogenic peptide of a soluble retinal antigen and to the homologous nuclear antigen, histone 3 (H3). ANA occur in most children with juvenile rheumatoid arthritis (JRA) and associated uveitis. An uveitogenic segment of retinal soluble antigen (S antigen peptide) is homologous with a similarly uveitogenic peptide of H3. We investigated a possible association between ANA positivity, antibodies to H3, and antibodies to the uveitogenic S antigen peptide. METHODS: The sera of 31 children with uveitis (20 of whom had associated JRA) were tested for the presence of ANA by indirect immunofluorescence. Antibodies to H3 and to an uveitogenic peptide of S antigen (an 18 mer segment having the amino acid sequence DTNLASSTIIKEGIDKTV) were measured by enzyme immunoassay. RESULTS: 19 of 20 children (95%) with JRA and associated uveitis and none of 11 with uveitis not associated with JRA had positive tests for ANA (X2 = 14.97; p < 0.00001). 16 of 19 ANA positive sera from subjects with JRA (84%) displayed reactivity with the chromosomal regions of metaphase cells. 9 of 20 patients with JRA with uveitis (45%) and 2 of 11 patients (18%) with uveitis not associated with JRA had antibodies to H3. Two uveitic patients with JRA (10%) and 2 non-JRA patients with uveitis (18%) reacted with S antigen peptide. Antibodies to H3 occurred significantly more frequently in children with uveitis than in all adult control subjects (X2 = 12.98; p = 0.003) and in adults with uveitis (X2 = 5.62; p = 0.022). CONCLUSION: Humoral immune responses to the uveitogenic peptide of S antigen and the homologous H3 antigen appear not to be uniquely important in the immunopathology of uveitis associated with JRA. Antibodies to isolated H3 do not exclusively account for ANA positivity in the uveitic patient with JRA. A unique immunopathogenic mechanism for the development of uveitis associated with JRA is suggested by the observations that (1) children with uveitis associated with JRA are more likely to be ANA positive than children with uveitis not associated with JRA, and (2) children with uveitis associated with JRA are significantly more likely to be ANA positive and to have antibodies to H3 than adults with uveitis.
7489326 The neuropeptide alpha-melanocyte-stimulating hormone: a key component of neuroimmunomodul 1994 Mar Recent research indicates that the proopiomelanocortin derivative alpha-melanocyte stimulating hormone (alpha-MSH) is a significant modulator of host reactions including fever and inflammation. Although the precise mechanism of action is still unknown, cytokine antagonism is believed to be responsible for at least a part of its anti-inflammatory/antipyretic influence: alpha-MSH antagonizes pyrogenic and proinflammatory effects of cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), and interferon gamma (IFN gamma). Although it is clear that the peptide can act within the brain to inhibit fever and peripheral inflammation, an anti-inflammatory effect on a peripheral target was evidenced in animals with transection of the spinal cord. Recent data show that alpha-MSH is significant also in human disorders such as AIDS, rheumatoid arthritis, and myocardial infarction. This molecule is believed to be a key factor in neuroimmunomodulation and it may be useful as a therapeutic agent in control of inflammatory reactions.
7508583 Monoarthritis in the rat knee induces bilateral and time-dependent changes in substance P 1993 Dec Bilateral changes in the spinal cord and dorsal root ganglion content of the sensory peptides substance P and calcitonin gene-related peptide have been previously reported in animal models of arthritis which affect many joints within the body. The central nervous system has been implicated in the symmetry of joint involvement in human rheumatoid arthritis. We aimed to determine whether unilateral inflammation of the knee joint can also induce bilateral changes in the spinal cord. We have induced a monoarthritis in the knee joint of the rat and used quantitative immunocytochemistry to look at changes of these peptides in the dorsal horn of the spinal cord and the dorsal root ganglia. Furthermore we have examined the responses during the acute (three days) and the chronic (21 days) phases of the model. The data show that in the acute phase of the monoarthritis there is both an ipsilateral and contralateral response which increases the immunoreactive substance P and calcitonin gene-related peptide in the L4 level of the dorsal horn of the spinal cord. In the chronic phase of the monoarthritis, the contralateral side of the dorsal horn returned to control values whilst the ipsilateral side showed reduced amounts of immunoreactive substance P and calcitonin gene-related peptide compared to controls. We propose that the acute response, at three days, to unilateral inflammation is appropriate and has evolved to protect an organism against the original insult ipsilaterally, and the possibility of subsequent insult contralaterally.(ABSTRACT TRUNCATED AT 250 WORDS)
9034866 Presentation of HLA class I-derived peptides: potential involvement in allorecognition and 1996 Dec Some 25 years ago, when purified HLA class I allotypes were first being analyzed, of major concern was that the papain used for solubilization might produce a mess of proteolytic fragments that would prove impossible to separate and sequence. Those fears proved unfounded (Parham et al. 1975), and the homogeneity of the preparations was sufficient to allow crystallization and determination of the three-dimensional structure (Bjorkman et al. 1987). Ironically the least ordered region of the electron density map provoked the most interest because it gave a first view of the diverse peptides bound by an MHC molecule. With this image a second chapter of HLA class I biochemistry began, its charge to determine the structures of bound peptides and their influence on the immune system. The extraordinary polymorphism of HLA class I heavy chains now seems quite manageable compared to the vast complexity of the peptides, and our present ignorance as to which ones are important for health and disease. The comparative weakness of most HLA class I associations with disease has made HLA-B27 an especially favored target for investigation, and more is known of the structure and peptide-presenting function of HLA-B27 than for any other HLA-B allotype (López de Castro 1994). Much of this information relates to the native HLA-B27 molecule and has been collected in the belief that disease is a direct consequence of its antigen-presenting function. If one subscribes to the relevance of the transgenic rodent models, this position has almost become untenable. For rats and mice 'non-functional' forms of HLA-B27 are the agents of disease, raising the possibility that B27-associated arthritis is induced by HLA class II presentation of a B27-derived peptide, a variant of the mechanism advanced for the classical HLA class II-associated diseases: type 1 diabetes, multiple sclerosis and rheumatoid arthritis (Gregersen et al. 1987, Roudier et al. 1989, Cucca & Todd 1996, Hall & Bowness 1996). Such speculation invites the obvious question as to whether other diseases associated with HLA class I and chronic inflammation, HLA-C and psoriasis for example (Tiilikainen et al. 1980, Yanagisawa et al. 1995), result from class II presentation of class I peptides.
8506275 Reduced expression of a human V beta 6.1 T-cell receptor allele. 1993 May 15 We have previously described an allelic polymorphism in the V beta 6.1 T-cell receptor gene. The V beta 6.1B allele is associated with disease in a subgroup of patients with juvenile rheumatoid arthritis. Limited sequence data demonstrated nucleotide differences that resulted in two amino acid changes between the two alleles in positions predicted to be important in major histocompatibility complex/antigen recognition. The present study demonstrates substantially reduced expression of mRNA from the disease-associated allele (V beta 6.1B) in peripheral blood and thymic tissue. The complete genomic sequence of both alleles revealed two additional amino acid changes in the V beta 6.1B gene as well as nucleotide differences in the promoter and intron. A cysteine-to-arginine substitution at position 92 in the disease-associated allele makes this a non-functional beta chain, since this conserved cysteine is involved with disulfide bonding to cysteine-23 to form an immunoglobulin-like domain structure, thus resulting in a potential hole in the T-cell receptor repertoire.
23511932 Risk estimation of disorders associated with coeliac disease. A 16-year Danish nationwide 1996 We studied the association between coeliac disease and other diseases in a cohort of 896 persons who were registered in the Danish National Registry of Patients during a 16-year period. The registry contains information on all discharge diagnoses from Danish somatic hospitals. The total number of observation years in the cohort was 7144 years. The background population was 5.1 million.The strongest association was found with diabetes mellitus, pancreatic diseases and dermatitis herpetiformis. A weaker association was found with small intestinal cancer, malignant haematological disorders, agammaglobulinaemia and rheumatoid arthritis. Conclusively, our population-based study supported the association between coeliac disease and several other chronic diseases, but a weaker association than indicated in other less comprehensive studies and case reports.
7497541 Fibromyalgia. 1995 Aug The article details the history, concept, definition and assessment of the still enigmatic condition of 'fibrositis' or, as it has more recently been called, 'fibromyalgia'. The concept and diagnosis became popular, especially in North America, in the 1970s, after the seminal publications of Hugh Smythe (1972) and Smythe and Moldofsky (1977). It is noticeable that there does not appear to be an early case report as there is for instance for gout, rheumatoid arthritis or certain vasculitides. This may be one reason why we still lack a commonly shared clinical image of the 'typical' case. After Smythe and coworkers, operational definitions and classification criteria were given by Yunus et al, Lautenschläger et al (both in 1989) and Wolfe et al in 1990. The latter received the endorsement of the American College of Rheumatology and are now the most widely used. They identify fibromyalgia as a musculoskeletal disorder with spontaneous widespread pain and exaggerated tenderness as prominent and distinctive features. The other two criteria sets refer to a different concept of fibromyalgia as a 'functional' or 'dysfunctional' disorder. These and other nosological differences pose problems for clinical as well as epidemiological research. They may be of minor importance if it is accepted that any present definition is arbitrary and that a wide range of possible elements are more relevant to research than a uniform concept of a disease called fibromyalgia.
7478311 Plasma transferrin receptor helps to predict iron deficiency in the anemia of chronic dise 1995 Jun A recent study by Ahluwalia and colleagues used a discriminant statistical analysis approach to determine that a combination of serum ferritin, plasma transferrin receptor concentration, and erythrocyte sedimentation rate was the optimal set of variables for differentiating iron deficiency and the anemia associated with chronic disease in a group of elderly women. Iron deficiency was defined as a significant response in hemoglobin concentration after iron supplementation. The findings of this study suggest that iron deficiency can be relatively common among elderly anemic women with rheumatoid arthritis. Use of these three biochemical measures should be clinically useful to differentiate iron deficiency in the anemia of chronic disease.
7791153 The effects of food on methotrexate absorption. 1995 Apr OBJECTIVE: To determine the effects of food on methotrexate (MTX) absorption in patients receiving MTX for the treatment of rheumatoid arthritis (RA). METHODS: Standard pharmacokinetic variables were determined in patients with RA after their usual maintenance dose of MTX, under fasting conditions and after they ate a standard breakfast. RESULTS: No significant differences in area under the serum concentration versus time curve, maximal MTX concentration after dosing (Cmax), time to Cmax), bioavailability, urinary MTX, renal clearance of MTX, or creatinine clearance were observed between the 2 dosing conditions. CONCLUSION: We observed no significant effect of food on MTX absorption or bioavailability. Patients may consume MTX without regard to meals.
7886520 The impact of rheumatology in the primary care setting: one rheumatologist's odyssey. 1995 Mar I report my experience during one 6-month period as the sole rheumatologist running a weekly clinic at a small community hospital. The report illustrates the impact of rheumatologic expertise in an environment well-served by generalists and other medical subspecialists. This experience identifies important gaps in the education of generalists in internal medicine residency training programs. In particular, the ability to recognize and distinguish patients with the two most prevalent rheumatic disorders, rheumatoid arthritis and osteoarthritis, must be taught to generalists more effectively by rheumatologists.
7748533 Synovial fluid parameters in normal and osteochondritic hocks of horses with open physis. 1994 Dec An investigation was carried out on most common synovial fluid parameters of normal and osteochondritic hocks of horses less than 12 months old in order to confirm the presence of an inflammatory process. Furthermore, a spectroscopic study was performed on synovial fluid from both normal and diseased hocks. A depolymerization of hyaluronic acid was demonstrated in synovial fluid from diseases joints, similar to that reported in human rheumatoid arthritis. A one month rest seem to normalize all parameters considered and in one joint, a return to normal infrared spectrum was demonstrated.
7736340 The 1994 Merck Frosst Award. Mechanisms of nonsteroidal anti-inflammatory drug (NSAID) ind 1994 Dec Nonsteroidal anti-inflammatory drugs are widely used for the treatment of osteoarthritis and rheumatoid arthritis, but their ability to cause gastrointestinal bleeding is a significant limitation to this use. A better understanding of the pathogenesis of gastric and intestinal injury induced by these agents will permit the rational design of anti-inflammatory drugs that spare the gastrointestinal tract. In this review, the mechanisms through which nonsteroidal anti-inflammatory drugs are believed to cause gastrointestinal ulceration are reviewed. Several strategies that are being employed to develop gastrointestinal-sparing drugs are outlined.
8300745 Cytokine regulation of metalloproteinase gene expression. 1993 Dec Matrix metalloproteinases belong to a family of zinc-dependent enzymes capable of degrading extracellular matrix and basement membrane components. Their expression is greatly modulated by cytokines and growth factors and involves the gene products of the Fos and Jun families of oncogenes. After extra(peri)cellular activation, their activity can be further controlled by specific tissue inhibitors of metalloproteinases. A correct balance between these regulatory mechanisms is necessary to ensure matrix remodeling in normal physiological processes such as embryonic development, but the overexpression of these enzymes may initiate or contribute to pathological situations such as cartilage degradation in rheumatoid arthritis or to tumor progression and metastasis. Delineation of the mechanisms of metalloproteinase and metalloproteinase inhibitors gene expression, understanding of their mode of interactions, and characterization of their patterns of expression in various tissues in normal and pathological states will lead to new therapeutic strategies to counteract the deleterious effects of matrix metalloproteinases in human disease.
8315841 [Acute monocytic leukemia following anti-lymphocyte immunoglobulin treatment in a patient 1993 May A 57-year-old female, who had a 14-year history of rheumatoid arthritis, developed aplastic anemia. Treatment with anti-lymphocyte globulin (ALG) and methylprednisolone pulse therapy achieved complete remission. However, twenty months after ALG treatment she developed acute monocytic leukemia. In spite of the chemotherapy, consisting of cytosine arabinoside and etoposide, she died of pneumonia. Recently, reports from Western countries have claimed that patients with aplastic anemia frequently develop clonal disorders following ALG treatment. To our knowledge, this is the first report in Japan of a case developing acute leukemia following ALG treatment.
7685614 Immunotherapy and other novel therapies, including biologic response modifiers, apheresis, 1993 May Immunologic manipulations under current investigation include various biologic agents and pheresis procedures. Second-generation monoclonal antibodies have been "humanized" to circumvent human anti-mouse antibody production or to carry toxin amplification. At present these studies focus on refractory rheumatoid arthritis and lupus nephritis. Interferons, prostacyclin, and tolerance-inducing or blocking peptides are filling difficult therapeutic niches. Of particular importance are remarkable results for interferon alfa-2b in mastocytosis, and iloprost in Raynaud's disease with digital ulcerations. Enhanced pheresis procedures with photochemotherapy involving psoralens and extracorporeal removal of specific autoantibodies may broaden the spectrum of pheresis applications. Dietary manipulations of fatty-acid intake and caloric restriction have also received attention.