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

ID PMID Title PublicationDate abstract
6306107 Analysis of the defects responsible for the impaired regulation of EBV-induced B cell prol 1983 Aug Diminished regulation of EBV-induced B cell proliferation by T cells from patients with rheumatoid arthritis (RA) is paralleled by diminished production of gamma-interferon in response to autologous but not allogeneic stimulation. We have shown that the adherent cell subpopulation within the autologous RA stimulators plays a major role in the RA defect. In analyzing the mechanisms responsible for the adherent cell effect in RA, we examined the contribution of prostaglandin production. Indomethacin treatment (1 microgram/ml) of the RA auto-MLR led to increased production of supernatant inhibitory activity (8% +/- 4 without, 57% +/- 4 with indomethacin), but had no significant effect on the inhibition of EBV-induced B cell proliferation by normal auto-MLR supernatants. Adding excess autologous adherent cells to the normal auto-MLR, however, led to an indomethacin-reversible decline in the production of the inhibitory factor without suppressing the auto-MLR proliferative response. The adherent cell effect could be reproduced by adding PGE1 or PGE2 (10(-8) to 10(-6) M) to the normal auto-MLR. PGE2 levels in 72-hr auto-MLR supernatants were similar in RA (4.2 +/- 1 ng) and normal control (3.6 +/- 0.5 ng/ml) supernatants. Because we could not detect differences in PGE production, we assessed the sensitivity of adherent cell-depleted normal and RA auto-MLR to exogenous PGE. Concentrations of 10(-7) to 10(-6) M PGE were needed to block production of the inhibitory factor by to normal cells, whereas only 10(-13) to 10(-12) M PGE1 completely blocked it in RA cell cultures. Thus, the defective production of gamma-interferon in the RA auto-MLR is, at least in part, due to enhanced sensitivity of the RA lymphocytes to adherent cell-produced prostaglandins.
6085320 [Immunomodulation by intravenous gamma globulin?]. 1984 Feb The continuous improvement of gammaglobulin preparations for intravenous use has lead to new potential therapeutic applications no longer based on the substitution of lacking specific antibodies. Especially high-dose administration may exert positive influences on pathologically altered immune functions. The theoretical basis and clinical facts are discussed.
4060904 [Assessment of the risk of occipitocervical dislocation in inflammatory rheumatic diseases 1985 May In this mainly retrospective study we examined by means of tomographic and computer tomographic findings various manifestations and courses of cranio-cervical subluxations in chronic inflammatory rheumatic diseases and the resulting neurological complications. Even in marked cranio-cervical subluxations neurological complications are rarely observed. More serious anterior atlanto-axial subluxation represents the highest risk for spinal cord injury as a result of the mobility of the atlas. A subsequent vertical (upward) atlanto-axial subluxation occurring particularly in serious courses of illness reduces this risk since it is generally to be found together with a fixation of the atlas. This also applies to a possible pseudobasilar invagination. As a result of our studies we found ways of using CT to achieve further information. We could also derive guidelines for the indication of operative treatment. In view of the further development of surgical methods and variations in operative risk dependent on the preoperative situation, these recommendations can only be provisional.
786296 Characteristics of patients with serum antibodies to extractable nuclear antigens. 1976 Sep A distinguishing feature of the mixed connective tissue disease (MCTD) syndrome is the presence in the serum of antibody in high titer to ribonucleoprotein (RNP). To determine whether this was an exclusive observation, a large rheumatic disease population was surveyed for the presence of antibody in high titer to extractable nuclear antigens (ENA) including RNP. Of 650 sera examined, 440 (from 240 patients) had antinuclear antibody. Only 39 patients had serum antibody to ENA in titers greater than or equal to 1:200 dilution. In 16 the anti-ENA was shown by RNAse digestion to be anti-RNP. Although many clinical and laboratory characteristics were similar in these two groups, the patients more closely resembled the previously described MCTD syndrome and, importantly, less often had severe renal and central nervous system disease manifestations. Thus the presence of serum antibodies to ENA that are predominantly RNAse-sensitive (anti-RNP) helps to identify a rheumatic disease syndrome and also appears to have prognostic value.
3921866 CT of the main ligaments of the cervico-occipital hinge. 1985 The results of a CT-anatomical correlative study of the main ligaments of the cervico-occipital hinge are reported. CT criteria of normal ligamentous structure of this region are presented in axial, coronal and sagittal views with a special attention to the transverse ligament of the Atlas. Examples of pathological transverse ligaments are illustrated and emphasis is laid upon the better statement CT allows in such cases.
6194293 Lectin-dependent and lectin-independent activities of human mononuclear cells that modulat 1983 Aug Human peripheral mononuclear cells (MC) secrete 2 soluble activities that modulate the growth of human synovial fibroblastic cells. A growth-suppressive, lectin-dependent activity is elaborated by the non-adherent population and its secretion begins before DNA synthesis is initiated in concanavalin-stimulated MC cultures. The elaboration of this activity is partially dependent on the presence of serum and it appears to be distinct from virus-induced human leukocyte interferon. The second activity is secreted spontaneously by the MC, under a variety of culture conditions including supplementation with homologous human plasma, and it enhances the growth of synovial fibroblasts. The rate of secretion of the growth-enhancing activity by the nonstimulated MC approximately parallels that of the inhibitory activity from the stimulated MC cultures. MC from patients with rheumatoid arthritis and from nonaffected individuals secrete similar concentrations of growth-stimulatory activity for the synovial fibroblasts.
6823455 Jaw claudication. Its value as a diagnostic clue. 1983 Feb Jaw claudication accompanies relatively few disorders, but it may be an important presenting feature that heralds serious underlying disease. In temporal arteritis, for example, jaw claudication rather than the classic finding of unilateral lancinating headache may be the distinguishing symptom. In the case reported here, jaw claudication was a prominent symptom for five months in a black woman. Temporomandibular joint disease can produce pain similar to that of jaw claudication, as can rheumatoid arthritis involving the temporomandibular joint in the elderly. Myasthenia gravis closely mimics jaw claudication, and parotid tumors can produce similar pain. Atherosclerotic narrowing of the external carotid artery proximal to the origins of the facial and maxillary branches is a rare cause of jaw claudication. Recognition of the importance of jaw claudication can lead to early identification of the underlying disease and quick initiation of therapy to avoid serious complications.
7444044 [Evaluation of the mineral content of peripheral bones (radius) by photon-absorption techn 1980 Oct The evaluation of the mineral content of peripheral bones by measuring the photon absorption of the radius has proven to be a valuable method for routine clinical work: for diagnosis, follow-up and control of therapy. While there was a significant difference in the findings of normal persons compared with those of patients suffering from osteoporosis, renal osteodystrophy, osteogenesis imperfecta and skeletal fluorosis, there was no difference between normals and these patients suffering from Bechterew, Scheuermann, coxarthrosis, spondylosis, skoliosis and rheumatoid arthritis. Normal values for the mineral content and width or the radius at the junction of the middle and lower third--based on 8000 examinations--are mentioned.
6794352 Serum C1q concentrations in rheumatic disorders. Early normalization during treatment of i 1981 Oct Serum C1q concentrations were studied in 78 patients with definite and classical rheumatoid arthritis (RA). No correlation could be made either with disease activity, with erythrocyte sedimentation rate or with rheumatoid factor titers. In contrast to these findings in RA, however, serial determinations of this complement component were of value in predicting the response to therapy in four patients with immunologically-mediated vasculitis. Initially both C1q and C3 were depressed in two patients with SLE, one with cryoglobulinemic purpura and one with HbsAg-positive serum sickness, each with acute vasculitis. Sequential studies following the institution of treatment showed in each case that C1q returned to normal while C3 remained low. These observations suggest that analysis of serum C1q is preferable to C3 in these disorders when used to predict clinical change and the response to treatment.
1085756 Preparation of various fractions from Mycobacterium smegmatis, their arthritogenicity and 1976 Cell walls of Mycobacterium smegmatis were able to produce much more severe arthritis in rats than the delipidated cells, whereas cell envelope and cell membrane fractions were unable to produce the disease. The lysozyme-solubilized product was able to produce mild disease with only 30% of incidence with an optimum dose, whereas the higher and the lower doses did not produce the disease. The rats immunized with cell envelope, cell membrane fraction and nonarthritogenic doses of lysozyme-solubilized product were protected against the subsequent homologous and heterologous challenge of delipidated cells. It was discussed that this preventative effect can be the result of antigenic competition between the arthritogenic and nonarthritogenic components of M. smegmatis. On the other hand, all the fractions separated here were able to serve as an immunoadjuvant in terms of inducing delayed hypersensitivity to ovalbumin in guinea pigs.
103558 Serum amyloid A protein in amyloidosis, rheumatic, and enoplastic diseases. 1979 Jan Serum levels of amyloid protein A (SAA) have been shown to be elevated in different types of amyloidosis and in rheumatic diseases by radioimmunoassay using 125 iodine labeled AA and anti-AA. SAA levels were elevated in both primary and secondary amyloidosis, but there were highly significant differences between these levels. In heredofamilial amyloid, SAA levels were within normal limits. While the mean SAA level was elevated in persons over 70 years, the fact that some persons in this age group had normal levels suggested that marked elevation after age 70 may be due to occult inflammatory or neoplastic disease. High SAA levels in patients with rheumatoid arthritis correlated, in most cases, with physician evaluation of disease activity and Westergren ESR. SAA levels in patients with systemic lupus erythematosus were lower than those in patients with rheumatoid arthritis, and most patients with degenerative joint disease had normal levels. Very high levels of SAA were found in patients with neoplastic diseases. Patients with carcinoma of the lung and bowel had much higher levels than patients with carcinoma of the breast. Determination of SAA levels may be of value in evaluating different forms of systemic amyloidosis, assessing the activity of rheumatic disease, and screening for occult inflammatory or neoplastic disease.
6213999 [T-lymphocyte subpopulations in chronic inflammatory rheumatism]. 1982 May Monoclonal antibodies to a series of human lymphocytes subpopulations antigens (OKT) specific of the peripheral T cells (OKT3), of the inducer population (OKT4) of the suppressor cytotoxic population (OKT 5, OKT8), and anti-Ia (OKI1) were used to study blood lymphocytes from 50 patients with active or inactive rheumatoid arthritis (RA) and from 23 patients with ankylosing spondylitis (AS). In RA patients, there is a significant decrease of the total T cell population (T3 +) with higher percentages of helper (T4 +) T cells than in controls. In active forms of the disease, there also is a decrease in the suppressor cytotoxic (T5 + and T8 +) subset with a significant increase of the immunoregulating ratios T4 +/T5 + or T4 +/T8 +. Elevated levels of Ia + lymphocytes are found in all RA patients. Corticosteroid treatment seems to erase these abnormalities. On the contrary in AS patients, no significant modification of the T cell populations was evidenced.
7282110 Immunoregulatory role of stress mediators in rheumatoid arthritis. 1981 May Eighteen patients suffering from chronic rheumatoid arthritis were selected for the present study. Plasma levels of stress hormones like catecholamines and cortisol were found to be elevated. At the same time reduction in percentage of E-rosette forming lymphocytes and an elevation in levels of major serum immunoglobulins (IgG, IgA and IgM) were observed. Certain other alterations in serum protein fractions were also noted. Probable role of these factors in the pathogenesis of this disease is discussed and attempts have been made to inter relate these findings.
316459 Comparative effectiveness of five analgesics for the pain of rheumatoid synovitis. 1979 Jul Utilizing 3 different methods for analyzing the results, a single dose double-blind crossover study of the effectiveness of 5 analgesics and placebo against the pain of rheumatoid synovitis in 30 subjects showed all active drugs superior to placebo by 1 analysis; aspirin, codeine and acetaminophen superior to both placebo and propoxyphene by a second; and aspirin alone superior to placebo and propoxyphene by a third. More side effects were reported from pentazocine than from other agents.
6993672 Benoxaprofen--dose-range studies using quantitative thermography. 1980 Fifty-four hospitalized patients with rheumatoid arthritis participated in a dose-range study comparing benoxaprofen with placebo and in a further study comparing benoxaprofen with indomethacin. Assessments were made after a "washout period" weekly for 3 wk. There was clinical improvement with time in both the placebo and active drug groups which was attributable to bed rest and hospitalization. Assessments of pain, function, and analgesic consumption showed that benoxaprofen had analgesic activity at all dose levels. Computerized thermography showed that, at a dosage of 600 mg daily, benoxaprofen had a significant antiinflammatory effect; this observation was confirmed by the comparison with indomethacin. No side effects were noted in patients taking benoxaprofen.
6697565 Idiotypic network: possible explanation of seronegativity in a patient with rheumatoid art 1984 Feb In order to explain long term seronegativity in certain patients with rheumatoid arthritis (RA), we looked for the presence of anti-idiotypic antibodies against rheumatoid factors (RFs). From a patient's serum with classical but seronegative RA, we isolated a low quantity of the IgG fraction which partially recognized polyclonal RF idiotypes. The purified Fab'2 anti-idiotypic antibodies were able to inhibit up to 48% of in vitro RF production by pokeweed mitogen stimulated lymphocytes from a patient's peripheral blood with seropositive RA. The two main conclusions of this study are: (1) this single patient with seronegative RA has serum antibodies directed against RF idiotypes and (2) these anti-idiotypic antibodies could be implicated in the generation of seronegativity.
3882289 Complement activation by antibodies to DNA in systemic lupus erythematosus measured by enz 1985 Mar An enzyme immunoassay to detect complement-fixing antibodies to DNA (CF-antiDNA) was developed. Of SLE sera, 64% had these antibodies as did 6% of 50 rheumatoid arthritis and 3.2% of 93 normal human sera. The mean CF-antiDNA level was higher in the sera of SLE patients with renal disease than those SLE patients who had no renal disease (P less than 0.0001), and higher in those SLE patients with active rather than inactive renal disease (P = 0.006). CF-antiDNA was more closely associated with renal activity than total IgG-antiDNA or CH50. These observations suggest that both the quality and quantity of anti-DNA antibodies play a role in the pathogenesis of renal disease, and that modern enzyme immunoassays help distinguish the relative importance of complement-fixing antibodies to anti-DNA from that of total anti-DNA.
6229226 Unusual manifestations of hypothyroidism. 1984 Jan Thyroid hormone exerts direct effects on essentially all of the organ systems of the body. Hypothyroidism is a frequently diagnosed endocrine disorder that has characteristic clinical signs and symptoms. In addition to these common manifestations, however, there are many additional manifestations of hypothyroidism that are less commonly acknowledged and include involvement of the hematologic, muscular, cardiac, and rheumatologic systems. It is important to recognize that these other organ systems may be involved and that the resulting disease states can dominate the clinical picture. As with the classic manifestations of hypothyroidism, these unusual manifestations respond to thyroid hormone replacement therapy. Thus, the importance of recognizing these signs and symptoms, as a result of hypothyroidism, is evident. This article emphasizes these less common manifestations of the patient with hypothyroidism, and, in addition, discusses the possible pathophysiologic mechanisms by which thyroid hormone deficiency can lead to organ system dysfunction.
4085154 Measurement of anti-cardiolipin antibodies by an enzyme-linked immunosorbent assay (ELISA) 1985 Dec We describe the development of a simple and highly sensitive double antibody sandwich enzyme-linked immunosorbent assay (ELISA) for measuring IgG and IgM anticardiolipin antibodies (ACA). Microtitre plates were coated with cardiolipin at a concentration of 45 micrograms/ml by evaporation under nitrogen. Non-specific binding of diluted sera was eliminated by blocking of plates with 10% fetal calf serum in phosphate buffered saline (PBS/FCS) for 2 h. Then sera (100 microliters) at a dilution of 1:100 were incubated in the wells for 1 h. Affinity purified goat anti-human IgG or IgM (100 microliters) at a concentration of 1 microgram/ml was subsequently added and allowed to incubate for 1 h; detection of ACA was achieved using an alkaline phosphatase conjugated rabbit anti-goat IgG reagent by reading the colorimetric yield at 405 nm after incubation with substrate. Reference serum pools were established to study reproducibility of the assay throughout its sensitivity range, and Standard curves were established. The quantitative normal range was 0-9.0 Anticardiolipin ELISA Units (AEU) for IgG and 0-8.0 (AEU) for IgM-ACA. A strong correlation was found between the ELISA and radioimmunoassay methods for measuring ACA of both IgG and IgM classes. Results from 65 patients with systemic lupus erythematosus (SLE) and 45 patients with seropositive rheumatoid arthritis are also reported. The advantages of the ELISA method for quantitative determination of ACA levels, should make it a useful and reliable method for clinical and experimental monitoring of patients with SLE and associated autoimmune disorders.
6607576 Lysozyme in the labial salivary glands of patients with rheumatoid arthritis. 1983 Nov Lysozyme (muramidase) levels in the saliva have previously been discovered to be elevated in patients with rheumatoid arthritis (RA), a fact which has been tentatively ascribed to immunological reactivity in the salivary glands due to RA. To characterize further the mechanisms involved in elevation of salivary lysozyme, labial salivary glands from 57 RA patients and from 43 healthy control (CO) subjects were assessed morphologically, using ANAE (acid alpha-naphthyl acetate esterase) stain for B, T and MPS cells, as well as by immunoperoxidase kits for lysozyme. In addition, lysozyme concentration in serum, saliva and lacrimal fluid was chemically determined. Lysozyme immunoreactivity was disclosed in the serous acinar cells and in the epithelium of intercalated ducts, but never in the striated ducts. No difference in the localization or intensity of the staining could be found between RA and CO series. Lysozyme levels were elevated in serum and in saliva, but not in lacrimal fluid of RA patients. The percentile distribution on B, T, and MPS cells was equal in both series. MPS cells, which are known to be a rich source of lysozyme, were fewer in glands showing lysozyme immunoreactivity than in lysozyme-negative glands. This is evidence against the suggested direct relationship between MPS cell counts and lysozyme concentrations in external secretions. The results are discussed in terms of the immunological reactivity in salivary glands of patients affected by RA, with special emphasis on the intimate co-operation of the different protective systems (IgA, beta 2-microglobulin, lactoferrin, and lysozyme) shown to be operative in such glands.(ABSTRACT TRUNCATED AT 250 WORDS)