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

ID PMID Title PublicationDate abstract
67824 Mixed connective tissue disease syndrome. 1977 May Fifteen patients with epidermal nuclear staining on direct immunofluorescence of normal skin and high titer serum antibody to ribonuclease-sensitive extractable nuclear antigen (ENA) had diffuse nonscarring and focal alopecia, abnormal pigmentation, swollen hands with sclerodactyly, and chronic cutaneous lupus erythematosus (LE) as the most common dermatologic features. Direct immunofluorescence of normal, unexposed skin revealed a particulate ('speckled') epidermal nuclear staining pattern in all 15 patients and subepidermal immunoglobulin deposits in 5. Ribonucleoprotein antibodies in high titer are associated with this characteristic type of epidermal nuclear staining. These findings provide easily detectable markers for a less aggressive subset of LE characterized by distinctive clinical and laboratory features consistent with mixed connective tissue disease.
2935832 [Myasthenia induced by D-penicillamine. Study of immuno-clinical correlations in 23 cases] 1985 Dec 28 Sera from 23 patients with D-penicillamine-induced myasthenia gravis (MG) contained antibodies directed against the human muscle acetylcholine receptor (anti-AChR) in 83% of the cases at the onset of the disease. Twenty-one were patients with rheumatoid arthritis. The anti-AChR antibody titers were comparable to those of sera from ocular MG patients and were related to the presence of clinical signs but not to their severity. The anti-AChR antibodies persisted in autonomous MG (5 cases) and disappeared in the other cases. The same phenomenon occurred for antinuclear antibodies detected in sera from 13 patients at the onset of the disease: anti-ss DNA 9/13, antinuclear 4/13 and anti-histones 7/13. The latter antibodies seem to result from, and follow the D-penicillamine treatment.
3939560 Evaluation of a simple immunodiffusion technique for quantitation of platelet-associated i 1985 Summer Platelet-associated IgG (PAIgG) was quantitated in 33 children with immune thrombocytopenia and platelet counts less than 100 X 10(9)/liter using a simple radial immunodiffusion (RID) assay. Elevated PAIgG levels were found in 76% (16/21) of children with acute idiopathic thrombocytopenic purpura (ITP), 88% (7/8) of children with chronic ITP, and all four children studied with systemic lupus erythematosus and thrombocytopenia. Normal PAIgG values were found in children with the following disorders: malignancy and chemotherapy-related thrombocytopenia; ITP in remission (platelet counts greater than 150 X 10(9)/liter); various nonimmune hematologic disorders and juvenile rheumatoid arthritis, these children having normal platelet counts. In children with acute ITP, elevated PAIgG values at initial presentation fell to within the normal range when clinical remission occurred. The RID assay can be easily established in most hematology laboratories and has the advantage that solubilized "test" platelets used in the assay can be stored frozen prior to analysis. We conclude that this simple technique is of value in the evaluation of childhood thrombocytopenic states and yields results comparable to those reported using more complex antiplatelet antibody assays.
6231966 A morphologic and immunologic study of the large granular lymphocyte in neutropenia with T 1984 May We report four patients with expansion of a unique population of lymphocytes that is consistently associated with neutropenia. Two patients also had rheumatoid arthritis and autoantibodies. The lymphocytes contained many cytoplasmic azurophilic granules, which possessed strong acid phosphatase activity. Multiple cytoplasmic parallel tubular arrays were observed ultrastructurally. These granular lymphocytes showed the T suppressor/cytotoxic cell phenotype (E+, OKT3+, OKT8+, OKT4-, OKM1-, OKI1-) and exhibited antibody-dependent cell-mediated cytotoxic activity but little or no natural killer cytotoxicity. They did not respond to recall antigens, concanavalin A, or pokeweed mitogen, but the cells from one patient did respond to phytohemagglutinin. No in vitro suppressor cell activity on mitogenic responses of allogeneic cells and on mixed lymphocyte cultures could be demonstrated. There was no evidence of suppression of immunoglobulin synthesis in vivo. It is uncertain that the expansion of this subset of lymphocytes represents a leukemic process. Their constant association with neutropenia, however, raises the possibility that the increase in large granular lymphocytes and neutropenia might be pathogenetically related.
6839931 Patterned anomalies of the retinal pigment epithelium: dystrophy or syndrome? 1983 Feb 28 Under the heading of patterned dystrophies of the central pigment epithelium have been included, in some recent publications, the reticular and macroreticular dystrophies described respectively by Sjögren and Mesker et al. (both probably autosomal recessive hereditary conditions) as well as Deutman's butterfly-shaped dystrophy and fundus pulverulentus (both with autosomal dominant heredity), occurring in a few families. We have recently seen 6 patients with patterned anomalies of the central retinal pigment epithelium. The cause of this pigment anomaly was different in each case: Stargardt's macular degeneration associated with fundus flavimaculatus, drusen of Bruch's membrane, choroidal folds, adult (non-hereditary) vitelliform degeneration, bull's eye degeneration of the macula in chronic rheumatoid arthritis, and detachment of the pigment epithelium. In only one case, that of Stargardt's degeneration, was the condition hereditary (autosomal recessive) so that the term dystrophy (= hereditary degeneration) would be justified; all the other cases were non-hereditary conditions. The central retinal pigment epithelium can only react in a limited number of ways to pathological stimuli: one way is the patterned distribution of pigment. This argues against the concept of patterned dystrophy of the retinal pigment epithelium, especially as under this heading conditions with different hereditary characteristics are lumped together.
7127940 Stress fracture of the patella following duopatellar total knee arthroplasty with patellar 1982 Oct Stress fracture of the patella can occur with significant frequency following patellar replacement with the duopatellar knee prosthesis. In the first 372 knees with patellar resurfacing, the incidence was 0.7% in rheumatoid arthritis (2 fractures in 286 knees) and 3.5% in osteoarthritis (3 fractures in 86 knees). The incidence may be greater in osteoarthritic patients because they have more function and are generating greater force across the patellofemoral joint. There was an association with osteonecrosis of the patella in at least three cases in which a lateral retinacular release had been performed and the lateral superior genicular artery sacrificed. This vessel should be preserved during a lateral release to save its contribution to the blood supply of both the patella and the lateral skin flap. Initial treatment of the stress fractures can be nonoperative, with surgery necessary only if the patellar prosthesis has become dislodged, or if pain or inadequate active extension persists. If the fracture can not be repaired, patellectomy can yield a good result. To avoid stress fracture, a minimal amount of patellar articular surface should be resected and the peripheral cortex of both the medial and lateral facets preserved. Fewer stress fractures may occur if a smaller fixation lug is used, thereby preserving more patellar bone stock.
7127837 The effect of ibuprofen on the excretion of steroid metabolites. 1982 Sep 1 An inexpensive gas chromatographic method is described that allows simultaneous measurement in urine of androsterone (A), aetiocholanolone (E), 11-hydroxyandrosterone (11-OA), 11-hydroxyaetiocholanolone (11-OE), pregnanediol (PD), pregnanetriol (PT), tetrahydrocortisone (THE) and tetrahydrocortisol (THF). Dehydroepiandrosterone was also resolved by the column. Ibuprofen was administered to five healthy normal males at a dose used therapeutically in rheumatoid arthritis (RA). The above urinary steroids were measured weekly during a control period, during a four week period of drug treatment and for four weeks after drug treatment had ceased. The excretion of A fell to a mean of 63% of the control value (p less than 0.02) and returned to the control value within two weeks. 11-OA, which showed a greater variability than A, fell to the same extent (p less than 0.1). No other steroid measured showed a change that could be related to the drug. This relatively limited effect of ibuprofen on steroid metabolism makes it a suitable drug for maintaining patients with RA during studies of their steroid metabolism.
9537063 Distribution of 'free' and HLA-associated human beta 2-microglobulin in some plasma membra 1980 The distribution of free and HLA-associated human beta 2-microglobulin (beta 2m) in serum, urine, spinal fluid, parotid duct saliva, seminal fluid, amniotic fluid and whey and in membranes from thrombocytes, lymphocytes, neutrophils and fat globules from milk was studied by crossed radioimmunoelectrophoresis (CRIE). The hydrophobic domain of HLA was demonstrable in 'charge-shift CRIE' and by binding to phenyl-Sepharose in 'hydrophobic-interaction CRIE'. In 'lectin-affinity CRIE' with concanavalin A and Lens culinaris lectin Sepharose the carbohydrate moiety present on. HLA exhibited heterogeneity as judged by the appearance of two partly separated protein peaks. Except for isolated fat globule membranes, HLA-associated beta 2m was present on all cells investigated. 'Free' beta 2m did not contain a hydrophobic domain as assessed by charge-shift and hydrophobic-interaction CRIE. All body fluids contained beta 2m in its 'free' form only. In serum, besides the free beta 2m, 2% was present as HLA-associated beta 2m, which, however, did not contain a hydrophobic domain. A degradation product of 'free' beta 2m, with alpha-mobility, was observed in sera from patients with malignant disorders, rheumatoid arthritis or systemic lupus erythematosus.
168002 Potential for clinical use of the analytical laser microprobe for element measurement. 1975 Aug Use of the laser microprobe for rapid emission spectroscopic analysis of elements in microscopic samples of biological material is described. The technique depends on vaporization of the microsample with a focused laser beam at a temperature that renders the vapor incandescent for spectrochemical analysis. Spectral line intensities are recorded photographically with densitometry of the negatives or photoelectrically. Current capability permits analysis of about 10(-8) to 10(-10) g of tissue, with detection limits of 10-12 to 10-15 g of element. Groups of elements can be simultaneously analyzed. Minimum sample preparation is required, and the analysis is done on the stage of a light microscope, usually on an air-dried sample on a plastic slide. We exemplify the technique in analysis of gold in cultured fibroblasts treated with gold salts and in human skin after treatment with gold salts for rheumatoid arthritis, in element changes in biopsies of transplanted human hearts, and in unique profiles of groups of elements in human cancer tissue.
3921718 The benefits of oral contraceptives. 1985 Apr
3970855 Thrombocytopenia in SLE and related autoimmune disorders: association with anticardiolipin 1985 Feb Anticardiolipin antibody levels were determined in 116 patients with systemic lupus erythematosus and related autoimmune disorders. Forty-three of these patients had a history of thrombocytopenia--36 of whom had SLE, three primary Sjögren's syndrome, two rheumatoid arthritis and two mixed connective tissue disease. IgG anticardiolipin antibody levels were raised in 31 (72%) of the 43 patients and IgM anticardiolipin antibody levels were raised in 19 (44%). There was a strong statistical correlation between thrombocytopenia and raised anticardiolipin antibody levels of both the IgG (P less than 0.001) and IgM (P less than 0.01) immunoglobulin classes. Of the 20 patients with the highest IgG anticardiolipin antibody levels 16 had a history of thrombocytopenia. We suggest that anticardiolipin antibodies may play a direct role in mediating platelet destruction in autoimmune disorders.
6320148 Post-menopausal osteoporosis and estrogens. Who should be treated and why. 1984 Feb 1 Estrogen deficiency after menopause results in loss of skeletal calcium and increased risk of bone fractures. Administration to postmenopausal women of a daily dose of 0.625 mg of conjugated equine estrogen, 1 mg estradiol-17 beta, or 0.15 mg ethinyl estradiol prevents these changes. The safety of long-term estrogen administration has not been established by large-scale controlled studies. Therefore, hormone treatment should be reserved for patients with symptoms of estrogen deficiency or for subsets of persons at increased risk of osteoporotic bone fractures. These include fair-skinned or lightweight persons, smokers, heavy drinkers, persons on prolonged corticosteroid therapy, and those with early menopause or rheumatoid arthritis.
6361366 [Selective IgA deficiency]. 1983 Nov Selective IgA deficiency may be defined as an inborn state characterized by a decrease of serum IgA levels below 8 IU/1 (approximately 5 mg/dl) which may be associated with clinical symptoms of disease. The frequency of this condition in the general population varies between 1 : 400 and 1 : 3000 in different countries. Patients with defects of chromosome 18, ataxia teleangiectatica and with connatal rubella syndrome have a high incidence of IgA deficiency. Inspite of the decrease in circulating IgA there are B-lymphocytes containing IgA molecules in the peripheral blood. Thus it has been concluded that transformation of B-lymphocytes into IgA bearing plasmacells is stunted by another mechanism. While small amounts of IgA may be released by transformed plasmacells the capacity of B-lymphocytes to mature into fully functioning plasmacells releasing normal amounts of IgA is defective. T-cells acting as suppressor cells for IgA differentiation have been demonstrated in peripheral blood and are a possible explanation for this phenomenon. The majority of individuals with IgA deficiency are healthy. Evaluations of increased susceptibility for infections have to consider the fact that 6 respiratory tract infections per year are the average for any preschool child. However a number of children with IgA deficiency suffer from recurrent bacterial infections such as sinusitis, bronchitis and pneumonia, usually responding well to antibiotic treatment. IgA deficiency has an established correlation with atopic disease. There is an 40 fold increase in incidence of allergies and autoimmune diseases such as rheumatoid arthritis, lupus erythematodes and thyroiditis in individuals with IgA deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
6866113 Myositis autoantibody inhibits histidyl-tRNA synthetase: a model for autoimmunity. 1983 Jul 14 In autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus (SLE), autoantibodies are generated against a variety of macromolecules. Myositis is a human autoimmune disease characterized by weakness and wasting of muscle. In American studies, antibodies directed against soluble cellular constituents were detected by immunodiffusion in about 60% of cases; the commonest of these, found in 25% of patients, was antibody to the Jo-1 antigen. An antibody system referred to as PL-1 was recognized at a similar frequency in a series of patients studied at Hammersmith Hospital, London. We show here that this system is identical with the Jo-1 system and demonstrate that the antigen is a polypeptide of molecular weight (Mr) 50,000. The protein is immunoprecipitated with tRNA His and appears to be histidyl-tRNA synthetase. The identity of the Jo-1 antigen, the first of the RNA-associated antigens familiar in autoimmune disease to be characterized as a specific enzyme, suggests a model for virus involvement in autoantibody generation.
6871542 Gold-containing drugs and the control of proteolytic enzymes. 1983 May 1 NaAuCl4 and aurothioglucose inhibited trypsin in free solution without the need of a carrier molecule. 2 NaAuCl4, aurothioglucose, aurothiomalate, auranofin and chloro-triethyl phosphine) gold all inhibited the trypsin-like neutral protease on the surfaces of Ehrlich ascites tumour cell membranes equally well. 3 Crude cathepsin preparations were activated by low concentrations of dithiothreitol and also by aurothioglucose, due to the displacement of an inhibitor. 4 Thiol-activated cathepsins were inhibited by each of the gold derivatives. The gold could be withdrawn from the enzyme by incremental additions of thiols such as reduced glutathione and cysteine with regeneration of enzymic activity. 5 Lineweaver-Burk plots of kinetic data indicated that gold acted as a non competitive inhibitor of cathepsins. 6 A naturally occurring inhibitor of cathepsins was extracted from cartilage. The mechanism of inhibition was again shown to be a thiol-disulfide exchange, the disulphide being provided by the inhibitor and the thiol being provided by the enzyme. 7 The role of gold in the attempted control of proteolysis in the rheumatoid arthritis is briefly discussed in terms of reversible exchange reactions involving gold thiols, disulphides and cartilage inhibitors of proteolytic enzymes.
6581529 Bioavailability of naproxen tablets and suppositories in steady state. 1983 Serum profiles were obtained from patients with rheumatoid arthritis after treatment with naproxen tablets and suppositories for 10 days to assure steady state conditions. The serum concentrations immediately before dose intake correlated well with the area under the concentration curve (AUC) when 250 mg naproxen tablets were taken 12-hourly (r = 0.85) and when 500 mg naproxen was given as tablets or as suppositories once daily in the evening (r = 0.83). These fixed times for blood samplings should be used in clinical trials with naproxen. Naproxen was measured by mass fragmentography. The mean steady state concentration and the mean half-life, calculated from the 12-hourly dosage schedule, were 45.0 +/- 1.7 mg/l and 15.2 +/- 1.4 hours, respectively. Doubling the dose from 250 mg to 500 mg b.i.d. increased the AUC by 30%. Average serum profiles for tablets and suppositories were very similar and gave a relative bioavailability of suppositories compared to tablets of 103% +/- 4%, suggesting comparable efficacy of the two administration forms.
6404137 Interleukin-2 and autoimmune disease. 1983 Interleukin-2 (IL-2) deficiency is a common feature of autoimmune disease in several inbred strains of mice genetically predisposed to a lupus-like illness, including four (MRL, C57Bl/6, AKR/J, and C3H/He) bearing the lpr gene. Defective production of IL-2 in response to concanavalin A can occur even when the proliferative response to mitogens is preserved. In C56Bl/6-lpr mice there is no apparent influence of the lpr gene and IL-2 deficiency on the induction of the experimental autoimmune myasthenia gravis that follows immunization with the acetylcholine receptor. The production of IL-2 by peripheral blood mononuclear cells stimulated with PHA is decreased in patients with systemic lupus erythematosus and rheumatoid arthritis.
7218239 Regional rheumatology practice in Umeå a northern Swedish experience. 1981 Jan In 1973 rheumatology was reorganized in northern Sweden and a new center was developed to serve a county of 240,000 inhabitants. The results of this development from 1973 to 1977 are reported. Although the number of rheumatic disease beds available was slightly reduced an increased staff was able to reduce the average duration of hospital stay from 42 to 15 d. This was true for all diagnostic groups, both for conventional hospital wards and a comprehensive day-ward center. Initially, rheumatoid arthritis (RA) had the highest priority and the number of patients with this diagnosis increased. However, after 3 yr RA was diagnosed in only 12% of new out-patients and other rheumatic disorders became more frequent among both out- and in-patients. New patients were referred almost equally from primary care and other hospital departments. Although only 20% of patients came with a provisional diagnosis, half of these were changed after examination by the rheumatology department. An increased demand for diagnostic services and a rapidly changing diagnostic pattern are 2 important factors to be considered in the planning of any new rheumatology center.
6931570 Utility analysis of a computer stored diagnosis index and other medical record data. 1980 Jun A computer-based system for storing items of medical record data including a complete coded list of diagnoses was established in 1971 for all patients admitted to a research-oriented medical ward. An analysis was made to assess the usefulness of such an electronically-stored data base from the stand-point of Unit activity, disease correlations, stability of diagnostic criteria, completeness of diagnosis lists and accuracy of coding. Over six years, 1972-77, there were 3569 admissions of which 1679 were first admissions. The most frequently made principal diagnoses were cerebrovascular accident (8%), myocardial infarction (5.4%), ischaemic heart disease (2.9%), rheumatoid arthritis (2%), duodenal ulcer (2%) and systemic lupus erythematosus (1.9%); the 33 most frequent principal diagnoses accounted for only 45% of all principal diagnoses made. The duration of stay (mean 16 days) was shown to depend on principal diagnosis but not significantly on age. Variability in annual incidence was significant for 24% of diagnoses; for some diagnoses this was readily explainable by extraneous causes, but for others it suggested an "instability" of criteria for that diagnosis. The probability of a minor diagnosis being "overlooked", using Dupuytren's contracture as an example, was shown to be high (50%). The rate of miscoding a diagnosis was 5%. This study, despite its illustration of the "softness' of diagnosis making in routine hospital ward practice, illustrates the potential or processing hospital diagnosis data by computer.
6160781 H2 antihistamines (cimetidine) and allergic-inflammatory reactions. 1980 Jun Experiments in the skin and synovialis have thrown new light on the allergic-inflammatory reactions. The inflammatory effect of histamine is thus due to stimulation of two different types of receptors in the vessels, i.e. histaminergic H1 and H2 receptors. Both types of receptors are of importance for the immediate cutaneous response to allergens and histamine. Treatment with a combination of H1 antagonists (classical antihistamines) and the H2 antagonist cimetidine will thus cause a much stronger inhibition of the urticarial reactions than treatment with the H1 and H2 antagonist alone. It is therefore probable that a combination therapy could have an advantage over the traditional treatment with classical antihistamines in urticaria and other histamine-mediated skin diseases. Histamine might also be of importance for the swelling of the joints in inflammatory diseases such as rheumatoid arthritis, and clinical trials with H1 and H2 antagonists are in progress.