Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2655541 | Advances in management of rheumatic disease. 1965 to 1985. | 1989 May | Advances in management of the rheumatic diseases over the past 20 years have been substantial. Over this period, survival of patients with systemic lupus erythematosus improved dramatically. Previously fatal renal crisis in scleroderma became treatable. Survival in Wegener's granulomatosis improved from 7% after 2 years to over 90%. Gout became an easily and effectively managed disease. Polymyalgia rheumatica became readily recognized and dramatically treatable. Less quantifiably, the shift toward more aggressive use of an increasing repertoire of "disease-modifying" agents in rheumatoid arthritis gave hope of having altered the natural history of the disease. Replacement of destroyed joints dramatically reduced pain and improved function in appropriately selected individuals. An increasingly broad mission of the National Institutes of Health has provided support for systematic evaluation of clinical management, including the Multi-Purpose Arthritis Centers, the American Rheumatism Association Medical Information System, and the Cooperating Clinics, effectively complementing research in fundamental mechanisms of disease. The role of the concerned clinician and the clinical epidemiologist in identification of new syndromes and new diseases and in innovating approaches to their management has been extremely important; this role appears far from over. | |
| 1840815 | Collagenopathic cardiopathies. | 1991 Oct | Collagenopathic cardiopathies are a subject of extreme etiologic, pathogenetic and clinical interest. These disorders are associated with congenital or acquired anomalies of the connective tissue and because of the diffusion and nearly total distribution of this tissue, have a higher frequency than what has been previously estimated. The collagenopathic cardiopathies, can be divided into two main groups: one deriving from hereditary connective tissue diseases, and the other from acquired connective tissue diseases. The first group has a Mendelian type of transmission whereas the other appears to be secondary to various kinds of stimuli (viral, immunologic etc.) although polygenic factors are present. Of the first group we considered Marfan's syndrome, the Ehlers-Danlos syndrome, osteogenesis imperfecta, pseudoxanthoma elasticum, cutis laxa and the diseases of the fundamental substance with particular reference to mucopolysaccharidosis type 1H (Hurler's syndrome). In all of these disorders a specific metabolic disturbance is responsible for the cardiovascular damage which is expressed, depending on the specific genetic component in a more or less serious form. Among the acquired diseases of the connective tissue, we examined rheumatoid arthritis, systemic lupus erythematosus, polydermatomyositis, scleroderma; of the reactive arthritis, rheumatic fever; of the seronegative forms, spondyloarthritis, ankylosing spondylitis and Reiter's syndrome, mixed connective tissue disease and Lyme's disease. It must be emphasized that all of these disorders share relatively common pathogenetic characteristics which point to the importance of the presence of various types of antigens, immune complexes and the significant role of some of the histocompatibility antigens, as well as possible disturbances of cell-mediated immunity.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2784964 | The effects of methotrexate on the production and activity of interleukin-1. | 1989 Apr | To explore the possibility that the mechanism of action of methotrexate (MTX) in rheumatoid arthritis (RA) is related to modulation of interleukin-1 (IL-1), the effects of MTX on IL-1 production and activity were evaluated. Human peripheral blood mononuclear cells and murine peritoneal and splenic cells were stimulated by lipopolysaccharide to produce IL-1. No inhibition of IL-1 synthesis or secretion caused by MTX treatment could be demonstrated either in vitro or in vivo, in patients with RA or in mice treated with MTX. We did show, however, that MTX had an inhibitory effect on IL-1 activity in 2 assays that demonstrate 2 different functions of IL-1. In a 2-step assay using LBRM-33-1A5 (1A5) and CTLD cells, MTX inhibited the secretion of IL-2 by 1A5 lymphoma cells in response to phytohemagglutinin and IL-1. In an assay using D10.G4.1 (D10) cells, MTX inhibited IL-1-induced proliferation of the D10 T cell clone. No effect of the drug on IL-2 activity was observed. The results demonstrate that MTX is capable of inhibiting some IL-1 activities without affecting IL-1 production or secretion. We propose that the inhibition of IL-1 activity or IL-1-dependent events may be one of the mechanisms of action of MTX in RA. | |
| 2660251 | Incidence of gastropathy in destructive arthropathies. | 1989 | Non-steroidal anti-inflammatory drugs (NSAIDs) are effective in relieving the symptoms of arthritis, but may have serious side-effects such as gastrointestinal lesions. This paper reviews the current status of knowledge concerning NSAID-induced gastropathy. In general, patients who present with bleeding peptic ulcers are more likely to be using a NSAID than are matched controls. The incidence of gastric lesions is increased in patients receiving more than one NSAID, suggesting a cumulative risk for these drugs. Endoscopic studies, which have attempted to relate the presence of a lesion to dyspeptic symptoms have shown a poor correlation, indicating a high risk of perforation and bleeding without prior symptomatic warning. Peptic ulcer disease is equally prevalent in patients with rheumatoid arthritis or with osteoarthritis, so the underlying condition does not appear to influence the onset of NSAID-induced gastropathy. Care is required when prescribing NSAIDs; they should not be used in trivial or self-limiting conditions or in existing cases of active peptic ulceration. In addition, caution should be exercised in patients with a history of peptic ulceration, and in the elderly. | |
| 2956665 | Rheumatic complaints in Tokelau. I. Migrants resident in New Zealand. The Tokelau Island m | 1987 | The three Tokelau atolls are 8 degrees south of the equator. In 1966 the islands were involved in a severe hurricane which drew attention to overcrowding and led to resettlement of more than half the population in New Zealand. One thousand three hundred and eighty one migrants over 15 years old were examined in New Zealand in 1980 and 1981 for rheumatic complaints as part of a continuing assessment. Clinical criteria for osteoarthritis (COA), including crepitus in any joint and in the knee, showed an increase in prevalence with age and weight in both sexes. Partial correlation coefficient analysis showed an association of the number of affected joints or the severity of knee COA (COAK) with both age and weight. Stepwise regression showed that age was the best predictor of both COA and COAK scores. Weight had predictive value only for COAK and only in women. Using the tracking method, previous high and/or increasing weight was related to COAK observed at this assessment. Heberden nodes increased with age and were more prevalent in women but were not associated with weight. Low back, dorsal and neck pain showed no association with age or sex. Low back pain was associated with weight. Joint pain following injury occurred in 15.4% of men. Gout, more common in men, was the only frequent inflammatory arthritis found. Two definite cases of rheumatoid arthritis (RA) were identified and four had criteria 1 and 2 for the New York criteria. | |
| 1786510 | Effects of paracetamol and aspirin on neural activity of joint mechanonociceptors in adjuv | 1991 Sep | 1. The effects of paracetamol and lysine acetylsalicylate (L-AS) on high-threshold mechanonociceptors have been investigated by recording neural activity from the inflamed ankle joint in anaesthetized rats with mild adjuvant-induced monoarthritis. 2. Paracetamol (50 mg kg-1, i.v.) and L-AS (100 mg kg-1, i.v., equivalent to 50 mg kg-1 aspirin) both caused a maximal reduction of about 40% in mechanically-evoked discharge and of 30% in ongoing (spontaneous) activity by about 15 min after the injection: a second dose of either drug did not have any significant additional effect on discharge. 3. The prostanoid IP receptor agonist, cicaprost (0.1-0.5 micrograms), increased both mechanically-evoked and ongoing discharge to pre-paracetamol levels when injected close-arterially 30-50 min after paracetamol, whereas prostaglandin E2 (PGE2) was relatively ineffective at restoring activity. 4. The results suggest that prostacyclin (PGI2) contributes to the sensitization of high-threshold joint mechanonociceptors in adjuvant-induced monoarthritis, and that paracetamol and L-AS both act to reduce discharge by inhibiting the synthesis of prostacyclin in the joint capsule. 5. Paracetamol has a direct peripheral action affecting joint capsule mechanonociceptors in rat adjuvant-induced arthritis which is very similar to that of the soluble aspirin preparation, L-AS. These findings, together with the existing literature concerning the anti-arthritic effects of paracetamol, are relevant to the treatment of chronic inflammatory disorders such as rheumatoid arthritis. | |
| 2247694 | [Still's disease in adults: diagnostic problems]. | 1990 Jul | Still's disease is a seronegative arthritis of children which, in a limited number of cases, can affect adults. The diagnosis of adult-onset Still's disease is characterized by high fever, arthritis and negative serologic tests for rheumatoid factor and antinuclear antibodies and by at least two minor symptoms (leukocytosis, evanescent rash, serositis, hepato- or splenomegaly, and lympho-adenopathy). Since many diseases present analogous manifestations and the adult-onset Still's disease is generally diagnosed by exclusion, we report two patients, aged 26 and 39, with Still's disease, the former with a classic clinical feature, the latter with a clinical feature characterized by severe hepatic abnormalities. The determination of histocompatibility antigens can be useful because some of them (HLA-DR4 in case 1 and HLA-DRw6 in case 2) are frequently associated with the adult-onset Still's disease. The role of anti-inflammatory therapy (acetylsalicylic acid, indomethacin, steroids) must be emphasized, whose efficacy can constitute the pathognomonic element on which the diagnosis of adult-onset Still's disease can be based in a proper clinical pattern. | |
| 3243506 | [Anti-rheumatic action of cysteine ethylester hydrochloride]. | 1988 Sep | Ethylcysteine showed a prophylactic effect on collagen-induced arthritis in rats at 100 mg/kg, p.o., and the effect continued even after stopping the administration. However, it was not dose-dependent. D-penicillamine showed no effect under the same condition. Ethylcysteine tended to inhibit collagen-induced arthritis when it was administered therapeutically at 300 mg/kg, p.o. Moreover, it had little effect on the acute inflammatory and type I allergy models such as carrageenin induced edema, 48 hr homologous PCA, and 6 hr and 24 hr Evans blue-carrageenin pleurisy in rats. In the in vitro assay, ethylcysteine had the following effects: inactivation of the rheumatoid factor, the acceleration of the denaturation of human gamma-globulin and the inhibition of bone alkaline phosphatase. The effect were as potent as those of D-penicillamine. As to the results, the mode of action of ethylcysteine is the same as that of D-penicillamine in terms of the biochemical properties. However, ethylcysteine showed an inhibitory effect on collagen-induced arthritis which was not demonstrated with D-penicillamine, so this drug may have a clinically anti-rheumatic action. | |
| 3589451 | [Lower costovertebral arthritis in rheumatic pelvispondylitis. Pseudourologic manifestatio | 1987 Mar | Costo-vertebral and costo-transverse joints are often involved during rheumatoid pelvispondylitis. Their involvement may lead to thoracic ankylosis and decreased respiratory capabilities. These arthritis may also cause intercostal or pseudo-visceral pains. The authors report three cases of lower costo-vertebral arthritis, revealed by pseudo-urological, acute or subacute pains. The diagnosis was made on clinical findings (especially mobilization of the lower ribs) and confirmed by X-Rays (especially tomodensitometry). One of the cases presents an image of unilateral pedicle opacity secondary to costovertebral arthritis. The pseudo-urological manifestation of the pain is likely explained by the anatomical relationship between costo-vertebral joints and the sympathetic communicating rami. This close anatomical relationship was confirmed by dissection. Through the communicating rami, the costo-vertebral joints are thus in relation with the sympathetic system, which is responsible for the sensory innervation of the renal space. The pseudo-urological revelation of this arthritis should be compared to that of costal sprains. | |
| 1865172 | Nephrocalcinosis in Sjögren's syndrome: a late sequela of renal tubular acidosis. | 1991 Aug | Sjögren's syndrome (SS) is an autoimmune exocrinopathy that develops into systemic autoimmune disease in 25% of patients, leading to general complications, one of which is kidney involvement. It presents mainly as interstitial nephritis, disclosed by hyposthenuria, distal renal tubular acidosis (RTA) and diabetes insipidus. We here describe five cases of SS with type-1 RTA (hyperchloraemic metabolic acidosis with an anion gap and alkaline urine pH) who developed nephrolithiasis, nephrocalcinosis and renal insufficiency. Hypercalciuria due to acidosis was the main nephrocalcinosis-prone factor in four patients; four subjects displayed diminished renal concentrating capacity, and two had hypokalaemia. | |
| 1929232 | The treatable dementia of Sjögren's syndrome. | 1991 Jul | Progressive dementia developed during a 15-month period in a 56-year-old woman with serologically and clinically documented primary Sjögren's syndrome. Findings from magnetic resonance imaging and angiography were normal, but a brain biopsy disclosed perivascular lymphocytic inflammation in leptomeningeal and parenchymal vessels. Treatment with high-dose corticosteroids produced rapid and nearly complete resolution of the dementia. | |
| 2571338 | Viral genomes in lymphomas of patients with Sjögren's syndrome. | 1989 Aug | The recent isolation of a new member of the herpes virus family (Human Herpes Virus-6, HHV-6) from patients with lymphoproliferative diseases prompted us to examine biopsies from six patients with primary Sjögren's Syndrome (SS) who developed non-Hodgkin's lymphoma. Five SS patients developed B-cell lymphoma and one developed a T-cell lymphoma based on immunoglobulin and T-cell antigen receptor (TCAR) gene rearrangements. In two SS patients with B-cell lymphomas, viral DNAs were detected, including: (a) Epstein-Barr Virus (EBV) DNA that exhibited an unusual pattern of restriction fragment length polymorphisms (RFLP) of the Bam M viral DNA segment; and (b) HHV-6 DNA in a second SS patient's lymphoma, with an RFLP similar to recent viral isolates from patients with other lymphoproliferative diseases. Viral DNA was not detected in the other four SS lymphoma biopsies. Also, all six biopsies were examined for presence of other viral DNAs (including CMV, HTLV, HIV and adenovirus) and were negative. Antibody titers to EBV-associated early-diffuse-antigen (EA-D), as assessed by ELISA method, and antibody titers against HHV-6, as detected by immunofluorescence and radio-immunoprecipitation assays, were markedly elevated in several SS patients with lymphoma and pseudolymphoma. These results suggest a potential role of EBV or HHV-6 in the neoplastic transformation that occurs with increased frequency in SS patients. | |
| 2551312 | A novel EBV-related nucleo-cytoplasmic antigen in a null cell-line (HLN-STL-C) reactive to | 1989 Aug | We have established a non-T- and non-B-cell line, HLN-STL-C(STL-C), which harbors the EBV genome, from the lymph node cells of a Japanese ATL patient. This cell line expresses a unique Epstein-Barr virus (EBV)-related nucleo-cytoplasmic (N-C) antigen which is detected by indirect immunofluorescence (IF) with the sera from patients with nasopharyngeal cancer (NPC), infectious mononucleosis (IM) or adult T-cell leukemia (ATL). One of the molecular components of this antigen is proved to be STL-C specific 125 kD molecule by immunoblot analysis (IB). To study the involvement of EBV in Sjögren's syndrome (SS), we examined the reactivity of the N-C antigen with the sera of SS patients by IF and IB. Among 24 cases examined, the sera of 21 cases (87.5%) positively stained the N-C antigen by IF. The staining patterns were divided into two types. Type I, (seven cases) showed positive staining for only N-C antigen, and Type II, (14 cases) was positive for N-C antigen associated with diffuse nuclear staining due to antinuclear antibodies in the SS patient's sera. Only one out of 11 non-Sjögren's patients' sera, which were almost all healthy controls, was positive for N-C antigen in this study. By IB, however, only two out of 15 IF-positive SS patients' sera reacted with STL-C specific 125 kD molecule. These results suggested the presence of heterogenous components in the N-C antigen. Our findings may support the hypothetical conception that EBV plays an etiological role in SS. | |
| 3369518 | Corneal infection in mucosal scarring disorders and Sjögren's syndrome. | 1988 May 15 | We reviewed 69 episodes of microbial keratitis occurring over an 11-year period in 56 patients with a mucosal scarring disorder or Sjögren's syndrome. Gram-positive bacterial isolates were the most common cause of infection, and accounted for almost all cases in patients with Sjögren's syndrome. Trichiasis (cicatricial pemphigoid), topical corticosteroids, bandage contact lenses, and corneal surgery were the main predisposing factors in the development of the corneal infection. In patients with ocular cicatricial pemphigoid, infection was much less common after chemotherapeutic control had been achieved. Recurrent infections were relatively frequent. There was a high rate of major complications, particularly in microbial keratitis complicating Sjögren's syndrome. | |
| 3476630 | Use of human minor salivary glands in basic and applied secretion research. | 1987 Feb | Previous findings from studies utilizing human labial and palatine minor salivary glands are reviewed. These studies took histopathological, biochemical, and ultrastructural approaches, and focused on control and diseased glands. Disease-oriented summarization are used, and control results are discussed in the context of disease-related findings. Findings are reviewed separately for electrolytes, macromolecules, and ultrastructure. In control subjects, minor gland salivary electrolyte concentrations are dependent on flow rate, and this dependence may be altered by diseases such as cystic fibrosis as well as by inflammatory situations such as graft-versus-host disease. There is also evidence that salivary electrolyte secretion processes are not similar in labial and palatine minor glands. Studies of salivary macromolecular composition are reviewed for control subjects and for patients with graft-versus-host disease and Sjögren's syndrome. The findings indicate that the macromolecular contents of labial and palatine gland saliva are similar, but that both are significantly different from that for major gland saliva. Finally, studies attempting to measure disease-related changes in intracellular composition are reviewed. It is concluded that the minor salivary glands are important models for the study of exocrine gland physiology and pathophysiology in man. | |
| 3462548 | Renal involvement in Sjögren's syndrome. | 1986 Aug 13 | Renal involvement is uncommon in Sjögren's syndrome. The case is reported of a woman with Sjögren's syndrome who developed renal failure, hypergammaglobulinaemic renal tubular acidosis and a renal tubular concentrating defect due to a severe tubulointerstitial nephritis. There was an impressive response to corticosteroid therapy. | |
| 3487648 | Familial abnormalities of lymphocyte function in a large Sjögren's syndrome kindred. | 1986 Apr | A large kindred (32 members), whose proband had primary Sjögren's syndrome, was investigated to ascertain whether abnormalities of lymphocyte function were present in family members of patients with Sjögren's syndrome. Ten members of the kindred with autoimmune diseases, 17 blood relatives, 5 spouses, and 32 matched controls were studied. Concanavalin A induced suppression of pokeweed mitogen stimulated immunoglobulin synthesis was decreased in patients and blood relatives both with and without autoimmune diseases. Elevations of the mean T4/T8 ratio, due to decreased numbers of suppressor/cytotoxic lymphocytes, were present in both the disease group and the blood relatives. These abnormalities occurred independently of HLA and were not necessarily associated with autoantibodies. | |
| 2389676 | Myopathy in Marinesco-Sjögren syndrome: an ultrastructural study. | 1990 | Seven muscle biopsies from patients with the clinical characteristics of Marinesco-Sjögren syndrome (MSS) revealed myopathic changes of two types; muscle fiber necrosis followed by regeneration and focal myofibrillar degeneration inducing autophagocytosis with rimmed vacuole formation. In two young patients, massive muscle fiber necrosis with phagocytic invasion was the predominant feature and autophagic phenomenon was minimal, resembling the findings in progressive muscular dystrophy. Myofibrillar degeneration with autophagic phenomenon was prominent in five adult patients. The coexistence of these two degenerative processes and the secondarily induced reactive changes of muscle fiber hypertrophy, interstitial fibrosis, occasional ragged-red fibers and type 1 fiber predominance, are responsible for the wide spectrum of muscle pathology in MSS. The dense double-membrane structure surrounding myonuclei, previously reported as being specific to MSS, was present in only one biopsy. | |
| 1917404 | Testosterone-induced suppression of autoimmune disease in lacrimal tissue of a mouse model | 1991 Oct | The current investigation was designed to examine whether androgen administration might suppress autoimmune disease in lacrimal glands of a mouse model (NZB/NZW F1) of Sjögren's syndrome. Autoimmune, female mice were treated with vehicle or varying concentrations of testosterone for 0, 17, 34, or 51 days, and tears, lacrimal glands, as well as submandibular tissue, were collected from killed mice after androgen exposure. Glands were histologically processed and evaluated with a computer-assisted image analysis system. Results showed that testosterone administration induced a significant, time-dependent decrease in the extent of lymphocytic accumulation in the lacrimal gland. After 34-51 days of androgen therapy, the magnitude of lymphocyte infiltration had been suppressed 22- to 46-fold, compared with that in placebo-treated tissue. This hormone effect was associated with significant reductions in the number of focal infiltrates, the area of individual foci, and the total quantity of lymphocyte infiltration per lacrimal section. Testosterone exposure also stimulated an increase in lacrimal gland weight and a rise in tear volumes, relative to those measured in the same mice before treatment. In addition, androgens significantly diminished the extent of lymphocyte accumulation in submandibular tissue. In summary, our results demonstrate that androgen administration may inhibit the progression of autoimmune disease in lacrimal and submandibular glands of NZB/NZW F1 mice. | |
| 2462349 | Major histocompatibility complex genes in systemic lupus erythematosus, Sjögren's syndrom | 1988 Dec 23 | Current concepts about the roles of human leukocyte antigen (HLA) and complement genes in predisposing to connective tissue diseases are reviewed. Precise localization of disease conferring alleles and epitopes is confounded by two major phenomena: (1) clinical and serologic heterogeneity of the diseases and associations of several different HLA alleles with different and often overlapping autoantibody responses; and (2) linkage disequilibrium of many potentially relevant gene loci located on the disease-associated HLA haplotypes. Using molecular genetic tools in serologically homogeneous patient populations, and across racial lines, the Ro (SS-A) and la (SS-B) autoantibody responses in systemic lupus erythematosus and Sjögren's syndrome appear to associate most strongly with HLA-DQ alleles, whereas the anti-Jo-1 autoantibody in myositis correlates best with HLA-DRw52. A gene deletion of C4A within HLA predisposes to systemic lupus erythematosus in both white and black patients. |