Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2464679 | Immunohistochemical analyses of autoimmune sialadenitis in man. | 1988 Sep | The immunoreactivity pattern for different monoclonal antibodies to cytokeratins and to vimentin in epimyoepithelial islands typical for glands of patients with Sjögren's syndrome has been compared with that of normal parotid gland tissue. Two types of epithelial island cells were observed: one had an intermediate filament protein pattern similar to that of ordinary duct epithelial cells of normal parotid gland. The other had an intermediate filament protein pattern typical of myoepithelial and/or basal duct cells in normal glands. Thus, we conclude that the islands are composed of a mixed population of gland cells on the basis of their content of cytokeratins or of cytokeratins and vimentin. These cells might originate from pluripotential reserve cells or from ordinary duct, myoepithelial and/or basal duct cells which may have undergone metaplasia. | |
| 3639739 | A human auto-immune antibody specifically recognizing initiator methionine tRNA from yeast | 1986 Aug 29 | Analysis of sera from 168 patients with autoimmune disorders revealed that one patient with Sjôgren's syndrome produced antibodies against deproteinized initiator methionine tRNA in addition to those against La protein. This anti-tRNAimet recognizes also tRNAimet from yeast but not from Phaseolus vulgaris chloroplasts (bean) or E. coli. It appears therefore that the epitope could be located in the TF loop in which an A residue in position 60 and the AUCG sequence are the only common features in yeast and human tRNAimet. | |
| 3625640 | Sjögren's syndrome: severe upper airways obstruction due to primary malignant tracheal ly | 1987 Jun | A wide spectrum of respiratory tract involvement may be seen in Sjögren's syndrome, however, multiple manifestations in one patient are unusual. A 65-year-old woman with a 5-year history of Sjögren's syndrome presented with hoarseness and pulmonary infiltrates. Lymphocytic interstitial pneumonitis, tracheobronchitis with subglottic edema and obstructive small airways disease were initially documented. Dramatic radiographic improvement of the lymphocytic interstitial pneumonitis occurred during 14 months of corticosteroid therapy. However, a rare primary malignant lymphoma of the trachea developed and presented with steroid refractory, upper airways obstruction. Subsequent patient management and the dichotomous behavior of the lymphoid infiltrates are discussed. | |
| 2539826 | Changes in the viscosity of hyaluronic acid after exposure to a myeloperoxidase-derived ox | 1989 Apr | Both purified hyaluronic acid (HA) and bovine synovial fluid react with OCI-, the major oxidant produced by the myeloperoxidase (MPO)/H2O2/CI- system, resulting in a decrease in their specific viscosity. This reaction is inhibited in the presence of excess methionine. H2O2 alone decreases the viscosity of HA, presumably by the Fenton reaction, in the absence (but not in the presence) of the iron chelator, diethyltriaminepentacetic acid (DETAPAC). In the presence of DETAPAC, incubation of HA with the complete MPO/H2O2/CI- system lowered the viscosity of HA. Analysis of 3H-HA exposed to OCI- by gel filtration chromatography indicated that cleavage of HA occurred only at higher OCI- concentrations. We suggest that the reduction in viscosity of HA by the MPO/H2O2/CI- system may be due to a combination of oxidative cleavage and changes in the conformation of the molecule. We speculate that the changes in the molecular size of rheumatoid synovial fluid HA may be due to the action of the neutrophil MPO/H2O2/CI- system. | |
| 1880781 | [Hemopigmented villonodular synovitis]. | 1991 Jun | Pigmented Villonodular Synovitis (PVNS) in an infrequent tumoral like disease and there are only a few MRI studies published. Concerning our series of five cases compared with the literature, the readers attention is drawn to the etiologies still under debate and to the respective contribution of the different imaging methods. MRI known for its high sensibility, but also for its low specificity in tumoral pathology, has turned out to be, in the case of PVNS, quite remarkable in both regards. The RMI aspect is quite well correlated to the histological structure of this synovial hyperplasia and to its evolution: highly vascular mass at the beginning and then low cellular density stroma, fibrous, with deposition of hemosiderin. In our five cases, as in almost all those previously reported in the literature, MR imaging shows heterogeneous areas of decreased signal intensity on T2 weighted sequences and on two of our cases after administration of gadolinium. Still the same MR aspects can be found in rheumatoid, hemophilic arthritis, as well as synovial chondromatosis, and therefore the clinical background and findings as well as plain films become essential. MR imaging should be the first examination to be undertaken after plain films, leading in most cases to a precise local preoperative assessment. | |
| 2635171 | A cytochemical study of the adjuvant inflamed air pouch in the rat. | 1989 | The oxidative biochemistry of the adjuvant-inflamed rat air pouch has been studied using the techniques of quantitative cytochemistry. Highly significant increases in the maximal activities of glucose-6-phosphate dehydrogenase, lactate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase were observed. These changes are similar to those that have been reported by others in both human rheumatoid synovial tissue and the synovial tissue of rabbits with allergic arthritis. It is suggested that modulation of these changes by putative therapeutic agents may form the basis for a readily quantifiable drug screening programme. | |
| 3496654 | [Surveys of the treatment and socio-professional future of patients with spondylarthritis. | 1987 Apr | After a brief historical reminder, the authors emphasize the difficulties of such investigations; difficulties of realization, analysis and synthesis since the results depend on ethnic and socio-cultural origins, socio-professional factors, primary or secondary forms or the length of evolution of the disease. From their experience, the authors draw a certain number of figures which they compare to those from other authors, especially concerning factors which aggravate the functional prognosis of the disease, or condition its complications. As for the therapy, considering the divergent opinions expressed about the results obtained with modern treatments, and used for thirty years, the authors have initiated an opinion survey among the members of the FSR (French Society of Rheumatology). The analysis of personal cases, the synthesis of various publications, the results of their survey, lead them to conclude that the problem of the treatment of ankylosing spondylo-arthritis and its professional consequences, is currently still more medico-social than scientific. The picture of rheumatoid pelvispondylitis seems less severe today than before, but it is necessary to have a longer follow-up to evaluate it statistically. | |
| 1751310 | Clinical manifestations of disease activity, its measurement, and associated morbidity in | 1991 Oct | Although nephritis remains a very important clinical disease manifestation of systemic lupus erythematosus (SLE), the focus has shifted from issues of mortality to morbidity. An improved method for measuring renal function is presented, and the value of renal biopsy, specifically the chronicity index, is confirmed as a predictor of end-stage renal disease. Several studies detailing the generally favorable course in SLE patients with renal failure who have eventually required chronic dialysis or renal transplantation are discussed. A high frequency of cardiovascular manifestations, often subclinical, is documented, including abnormalities of ventricular and valvular function. The clinical course and response to treatment of SLE patients with diffuse interstitial lung disease and pulmonary hypertension are outlined. Cases of the unusual gastrointestinal presentation of protein-losing enteropathy in SLE have been described by several authors. The clinical correlates and significance of persistent rheumatoid-like arthritis and radiologic erosive and cystic bony lesions in SLE are discussed. Serologic markers of specific SLE disease manifestations and general predictors of disease activity are evaluated. Complications related to infection, malignancy, and pregnancy are described. | |
| 3129704 | Bronchiolo-alveolitis with pulmonary basal lamina injury in a rheumatoid patient during go | 1988 Feb | A 47-year-old housewife presented with nonproductive cough, progressive breathlessness and intermittent fever during gold treatment, originally prescribed for seropositive polyarthritis, which later fulfilled the criteria for systemic lupus erythematosus (SLE). An open lung biopsy showed abundant interstitial edema with mononuclear inflammatory cells and some eosinophils, and slight bronchiolitis. The picture was nonspecific but suggestive of hypersensitivity pneumonitis. Electron microscopy revealed splitting and local disappearance of the basal laminae of the alveolar capillaries, venules and alveolar epithelium. This injury was confirmed by immunohistochemical staining for type IV collagen and laminin, the major components of basal laminae. In most macrophages there was lysosomal electron dense granular material, i.e. aurosomes, which gave the spectrum of gold in electron microprobe analysis. After the gold treatment was stopped the pulmonary symptoms gradually decreased during several months and no permanent lung disease remained. Whereas the pulmonary manifestation could have been due to her underlying disease we discuss in this study the possibility of its being gold induced. | |
| 3293572 | Hybridoma lupus autoantibodies can bind major cytoskeletal filaments in the absence of DNA | 1988 Jul | A panel of 65 systemic lupus erythematosus (SLE) and 61 normal-derived human hybridoma auto-antibodies was studied for cytoskeletal reactivity, using an indirect immunofluorescence method. Reactivity with the cytoskeleton was expressed 3 times more frequently in the SLE-derived antibody group and included intermediate filaments, microfilaments, microtubules, and centrioles. By immunoblot analysis, the antigenic specificity of intermediate filament-reactive SLE hybridoma antibodies was not restricted to vimentin, but included cytokeratins and desmin. The antibodies were also studied for their DNA-binding, lupus anticoagulant, and rheumatoid factor activities. These autoantibody activities were expressed 3-5 times more frequently in the SLE-derived group. The ability to bind DNA was not a prerequisite for reactivity with intermediate filament proteins. Our findings suggest that there are at least 2 subsets of cytoskeletal-reactive hybridoma antibodies: those that recognize epitopes found only on cytoskeletal proteins, and those that recognize epitopes common to both DNA and certain cytoskeletal proteins. In addition, we hypothesize that there may be a third subset of antibodies that recognize a phosphate-containing moiety (phospholipid or phosphoprotein) associated with cytoskeletal filaments. | |
| 2171482 | Development of an IgM antibody capture test using labelled fusion protein as antigen for d | 1990 Aug | A new anti-B19 IgM ELISA was developed using the antibody-capture principle. Biotinylated fusion protein was used as antigen. The specificity of the test was analysed using sera IgM positive to rubella, hepatitis B core antigen, cytomegalovirus and Epstein Barr virus as well with sera positive for rheumatoid factors, antinuclear antibodies and with sera from normal blood donors. The specificity of the test was 96.18%. One hundred serum samples were tested by the new ELISA and the standard MACRIA tests for the presence of B19 IgM. Eighty-eight sera gave the same results with both tests. Fifty-three were negative and 35 were positive. Six sera were ELISA negative MACRIA positive and six MACRIA negative ELISA positive. In a clinical study with 725 sera from suspected B19 infections, 161 (22%) were recorded as positive by the ELISA test. The positive sera were from patients suffering from arthritis (35%), rash (35%), acute or chronic erythroblastopenia (21%), pancytopenia (5%), vascular purpura (2%) and lymphadenopathy (2%). | |
| 1899430 | Selective expansion of human gamma delta T cells by monocytes infected with live Mycobacte | 1991 Feb | Gamma delta (gamma delta) T cell receptor (TCR) expressing T cells comprise 3% of human peripheral blood lymphocytes, yet their role in the immune response remains largely unknown. There is evidence both in humans and in animal models that these cells participate in the immune response to mycobacterial antigens. In mice, exposure to mycobacterial antigens leads to the expansion of gamma delta T cells in draining lymph nodes and lungs. In humans, gamma delta T cell lines with reactivity to mycobacterial antigens have been derived from synovial fluid of a rheumatoid arthritis patient, skin lesions of leprosy patients, and peripheral blood of a healthy tuberculin reactor. Very little is known, however, about the factors which induce human gamma delta T cells to expand. In studies comparing the human T cell response to live and heat-killed Mycobacterium tuberculosis (MT), we have found that monocytes infected with live MT are very effective inducers of human gamma delta T cell expansion. After 7 d of exposure to live MT, gamma delta T cells were greatly increased in all healthy tuberculin reactors (PPD+) tested and frequently were the predominant T cell population. In contrast, heat-killed MT or purified protein products of MT induced a CD4+, alpha beta TCR+ T cell response with very little increase in gamma delta T cells. Furthermore, a similar selective induction of gamma delta T cells was observed when monocytes infected with live Salmonella were used to stimulate T cells. Heat-killed Salmonella, like heat-killed MT, induced a predominantly CD4+ alpha beta TCR+ T cell response. These findings suggest that human gamma delta T cells are a major reactive T cell population during the early stages of infection with living intracellular bacteria and are therefore likely to exert an important role in the initial interaction between host and parasite. | |
| 2589399 | The anemia of chronic disease: spectrum of associated diseases in a series of unselected h | 1989 Dec | PURPOSE: Previous studies of the anemia of chronic disease (ACD) have generally begun with patients afflicted with one of the classical underlying diseases such as rheumatoid arthritis. The clinical spectrum of ACD has not been thoroughly examined. We hypothesized that many patients have an anemia with the characteristics of ACD but do not have one of the infectious, inflammatory, or neoplastic disorders usually associated with ACD. We therefore evaluated a series of consecutive, unselected, anemic patients admitted to a county hospital. PATIENTS AND METHODS: All patients admitted to the medicine ward service of a county hospital were screened for anemia (hematocrit less than 40% in men, less than 37% in women). Additional laboratory data were collected on all anemic patients, except those with active gastrointestinal bleeding, hemolytic disease, or leukemia or multiple myeloma. The patients were divided into three groups on the basis of serum values indicating iron distribution: iron deficiency (serum ferritin less than 10 ng/mL), ACD (serum iron less than 60 micrograms/dL and serum ferritin more than 50 ng/mL), and all others (non-ACD). The hospital records of the patients in the latter two groups were reviewed and their diagnoses recorded. RESULTS: Seven patients with iron deficiency were not considered further. Ninety patients with ACD were compared with 75 patients with non-ACD. The anemia in ACD patients was more severe than most authors describe. The mean hematocrit was 31%, and 20% of patients had hematocrits below 25%. The anemia was usually normocytic (mean red cell volume [MCV] 86 fL), but 21% had an MCV less than 80 fL. The level of saturation of serum iron-binding capacity was quite low in ACD (mean 15%) and was normal in non-ACD (mean 31%). Renal insufficiency was common in both groups; serum creatinine values were more than 2 mg/dL in 31% of patients with ACD and 20% of non-ACD patients. Sixty percent of patients with ACD had a principal diagnosis that fell into the infectious, inflammatory, and neoplastic categories commonly associated with ACD. Renal insufficiency was the major diagnosis in 16%, and the principal diagnosis in 24% was a disease not commonly considered to be associated with ACD. In non-ACD patients, the principal diagnosis was an infectious, inflammatory, or neoplastic disease in 55%, renal insufficiency in 9%, and another disease in 36%. CONCLUSIONS: When ACD was defined by the abnormalities of iron distribution, which are its most consistent and widely accepted characteristics, the spectrum of associated diseases was much broader than the traditional categories of infectious, inflammatory, and neoplastic disorders, and the overlap with non-ACD was large. Until the etiologic and pathogenetic mechanisms of ACD are better understood, a flexible and inclusive view of this disorder seems appropriate. | |
| 2682375 | [Significance of anticardiolipin antibodies in connective tissue diseases]. | 1989 Oct | Recent attention has focused on the possibility that the presence of Anticardiolipin Antibodies (ACA) in patients with connective tissue diseases, particularly with Systemic Lupus Erythematosus (SLE), may be associated with clinical and serological symptoms that identify a particular subset of patients. This group is characterized by recurrent arterial and/or venous thrombosis, multiple abortions and or intrauterine fetal death, presence of Lupus AntiCoagulant (LAC), false positive VDRL, thrombocytopenia and neuro-psychiatric diseases. These clinical features may identify the so-called "Anticardiolipin Syndrome". In this work, we have measured ACA, by ELISA test, in 194 serum samples: 97 SLE patients, 5 Mixed Connective Tissue Disease (MCTD), 8 Progressive Systemic Sclerosis (PSS), 7 Dermato/PolyMyositis (D PM), 3 Sjögren Syndrome (SS), 3 Unclassifiable Connective Tissue Disease (UCTD), 9 Rheumatoid Arthritis (RA), 1 Idiopathic Anticardiolipin Syndrome, 19 cases of Miscellanea, 42 healthy controls. The Optical Density (O.D.) was greater than 0 (higher than 0) in 89 serum samples (out of the 194): 43 SLE, 4 MCTD, 4 PSS, 3 D PM, 1 SS, 7 RA, 10 cases of Miscellanea, the Idiopathic Anticardiolipin Syndrome and 16 healthy controls. The O.D. was greater than m (greater than mean healthy controls level) + 3 Standard Deviations (S.D.) in a restricted number of cases (25 out of the 194): 14 SLE, 2 MCTD, 1 PSS, 1 D/PM, 1 SS, 1 RA, 3 cases of Miscellanea and 2 healthy controls. Therefore, we have noticed, first of all, the lack of specificity of positive results obtained: all the groups of patients, healthy controls included, had low as well as high levels of ACA. Moreover, we have examined the relationship between the presence of ACA and typical clinical features of the so-called. "Anticardiolipin Syndrome"; there was not difference of clinical symptoms between patients with low or high ACA levels. We have also clinically examined ACA negative patients; most of them had one or several clinical features of the "Syndrome", until almost complete clinical picture. Therefore, no correlation was found between clinical picture and immunological features of the so-called "Anti-cardiolipin Syndrome"; we would not exclude the existence of the "clinical" subset of patients, but of the "immunological" subset. | |
| 2784628 | Inherited diseases in North American Mennonites: focus on Old Colony (Chortitza) Mennonite | 1989 Feb | The patterns of migration and the genetic disorders occurring among North American Mennonites are reviewed, and inherited conditions recently recognized in a religious and genetic isolate, the Old Colony (Chortitza) Mennonites, are described. Old Colony Mennonites are of Dutch/German origin and descend from approximately 400 founding families who settled in the Old Colony, Chortitza (the Ukraine, USSR) in the late 1700s, and then migrated to Canada and Central and South America in the past century. We investigated over 6 generations of a Canadian Old Colony kindred in which there was extensive intermarriage, and in whom 28 individuals developed diabetes mellitus. Insulin-dependent diabetes mellitus (IDDM) occurred in 14 affected individuals in 10 closely related sibships; the 11 living IDDM patients were all concordant for the immunogenetic marker HLA-DR4. Fourteen close relatives had other disorders of carbohydrate metabolism, including gestational diabetes and non-insulin-dependent diabetes mellitus. Other close relatives had autoimmune diseases, including rheumatoid arthritis, hyper- and hypothyroidism, multiple sclerosis, and red cell aplasia. Other inherited diseases, including Alport syndrome, congenital defects, and inborn errors of metabolism were also found in the kindred. In the almost exclusively (99%) Old Colony Mennonite public health district in which the kindred was ascertained, there were multiple cases of Tourette syndrome, of malformations (including congenital heart defects and cleft lip +/- palate), and familial clusters of inborn errors of metabolism. We report this Old Colony (Chortitza) Mennonite isolate because 1) there are large familial aggregations of tissue-specific autoimmune diseases, malformations, inborn errors of metabolism, and of some other conditions whose genetic basis is still unknown; 2) there are multiple cases of rare genetic conditions, 3) we have established a computerized genealogic data base on over 1,000 kindred members as well as a cryopreserved lymphocyte/DNA bank on over 100 closely related individuals with various genetic conditions; and 4) this religious isolate, which extends across North, Central, and South America, offers an excellent opportunity for studying the epidemiology and molecular genetics of both common and rare inherited diseases. | |
| 2509855 | Gamma heavy chain "disease": heterogeneity of the clinicopathologic features. Report of 16 | 1989 Nov | This review underscores the diversity of the clinical manifestations and hematopathological features of gamma heavy chain disease based on the detailed report of 16 patients evaluated in our chemical department, the analysis of 12 cases diagnosed in our laboratory, and the study of 81 cases previously reported. This condition is defined by the presence in the serum of immunoglobulin molecules composed of deleted gamma heavy chains devoid of light chains. The production by the monoclonal B cells of these peculiar proteins appears to result from multiple defects (deletions, insertions, and mutations) in both heavy and light chain genes leading to abnormal mRNA splicing. Gamma heavy chain disease is currently underdiagnosed. The diagnosis established by immunoelectrophoresis using specific antisera combined, in some instances, with the immunoselection procedure, can easily be missed on serum electrophoretic patterns: a narrow abnormal band suggestive of a monoclonal component was found in only 10 of our 28 cases. The amount of heavy chain disease protein in urine ranges from trace to 20 g/day and is usually moderate. Gamma heavy chain disease most often presents as a lymphoproliferative disorder featured by lymphadenopathies, splenomegaly, and constitutional symptoms. Extra-hematopoietic tumor localizations, such as cutaneous or subcutaneous involvement or thyroid tumor, may occur. Autoimmune disorders, notably rheumatoid arthritis and autoimmune hemolytic anemia or thrombocytopenic purpura, are frequent (26% of cases). There is no specific histological pattern. The most frequent is a pleomorphic malignant lymphoplasmacytic proliferation mainly seen in bone marrow and lymph nodes. Some cases present with a predominantly plasmacytic proliferation or chronic lymphocytic leukemia. Other patients are affected with non-Hodgkin lymphoma of various morphologic types. Immunocytologic studies showed that a gamma heavy chain disease protein may occur in the context of a double monoclonal lymphoproliferative process or in various B or T cell malignancies that are not directly involved in the production of the abnormal immunoglobulin. In some patients, the histologic appearance of the enlarged lymphoid organs showed only a moderate lymphoplasmacytic infiltration of uncertain malignancy. More important, some patients showed no evidence of an underlying lymphoproliferative disorder after several years of follow-up. The clinical course of gamma heavy chain disease varies from an asymptomatic state to a rapidly progressive malignancy. The choice of therapy should entirely rely on the underlying clinicopathologic features, without taking into account the presence of the abnormal protein.(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 3493110 | Extrarenal synthesis of 1,25-dihydroxyvitamin D: sensitivity to glucocorticoid treatment. | 1987 Mar | The response of circulating 1,25-dihydroxyvitamin D [1,25-(OH)2D] to challenge with vitamin D treatment both before and after 7-10 days of prednisone therapy (25 mg/day) was investigated in five anephric subjects, six patients with chronic renal failure (CRF), two patients with vitamin D intoxication and four patients with hypoparathyroidism. In anephric subjects serum 25-hydroxyvitamin D [25-(OH)D] rose from 58 +/- 48 (SD) to 377 +/- 221 (SD) nmol/l after administration of 150 micrograms of 25-(OH)D3 for 1 month. Serum 1,25-(OH)2D, which was barely detectable in only two out of five patients under basal conditions, rose to 30 +/- 21 pmol/l after 2 weeks of therapy with 25-(OH)D3, but fell to 10 +/- 5 pmol/l during prednisone treatment. In CRF patients circulating 1,25-(OH)2D rose from 37 +/- 24 to 58 +/- 24 pmol/l during 25-(OH)D3 therapy, but fell to 41 +/- 31 pmol/l during prednisone treatment. In two patients with rheumatoid arthritis, hypercalcaemia due to vitamin D intoxication was associated with raised levels of 1,25-(OH)2D (288 and 317 pmol/l). Administration of prednisone resulted in suppression of 1,25-(OH)2D levels (132 and 96 pmol/l respectively) and reduction of serum calcium to within the normal range. In the hypoparathyroid patients prednisone therapy did not affect circulating 25-(OH)D levels but serum 1,25-(OH)2D fell from 192 +/- 42 to 117 +/- 23 pmol/l and serum calcium from 2.41 +/- 0.21 to 2.20 +/- 0.05 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 1889457 | Tolerance to a self peptide from the third hypervariable region of the Es beta chain. Impl | 1991 Sep | As a first step in the analysis of a molecular mimicry model of rheumatoid arthritis, we addressed the question of whether tolerance to self-major histocompatibility complex (MHC) class II molecules includes tolerance to peptides from the third hypervariable region of their beta chain. We studied T cell responses to a peptide from the third hypervariable region of the Es beta chain, Es beta peptide (PEFLEQRRAAVDTYC), in different mouse strains after footpad priming with peptide in complete Freund's adjuvant. Strains of mice of the k or d haplotype (B10D2; H-2d, B10BR; H-2k) mounted a vigorous T cell response to the Es beta peptide. In mice expressing the Es beta chain either on the cell surface (B10S9R) or in the cytoplasm as free unassociated chain (B10S), no response could be detected. Binding studies using purified MHC class II molecules and competition for antigen presentation showed that the Es beta peptide binds Ak, Ad and As but not Ek. Thus, the nonresponder status of B10S and B10S9R mice appears to reflect self tolerance. Tolerance was also suggested by the observation that responder x nonresponder F1 crosses such as (B10D2 x B10S9R) and (B10BR x B10S9R) did not respond to Es beta peptide. Interestingly, mice derived from the (B10BR x B10S) cross responded to the Es beta peptide, suggesting that the immune system may not always tolerate peptides from the third hypervariable region of self-MHC class II molecules. | |
| 2354868 | Release of platelet-activating factor in systemic lupus erythematosus. | 1990 | The biologically active 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (platelet-activating factor; PAF) is inactivated in plasma mainly by a specific PAF acetylhydrolase (1-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine acetylhydrolase; EC 3.1.1.48). In the present study, PAF was released in detectable amounts (5.4 +/- 2.9 ng/ml; mean +/- 1 SD) in the plasma of 8 out of 10 patients with systemic lupus erythematosus (SLE) during the most active phases of the disease. PAF was never detectable in the plasma of patients with inactive SLE or of healthy subjects. PAF acetylhydrolase activity was markedly reduced in sera of 10 patients with active SLE as compared to 7 patients with inactive SLE, 16 patients with rheumatoid arthritis (RA), 5 patients with nephrotic syndrome (NS) and 15 healthy subjects. A kinetic study of the enzyme in patients with active SLE suggested an overall reduced activity rather than an intrinsic defect of the enzyme. PAF acetylhydrolase in sera of patients with active SLE shared with that of healthy subjects the same substrate specificity, sensitivity to enzymatic and chemicophysical treatments and association to low-density lipoprotein (LDL), acting as carrier of PAF acetylhydrolase in plasma. However, the protein concentration of LDL was significantly reduced in patients with active SLE as compared to patients with inactive SLE, RA and NS and to healthy subjects, thereby suggesting that the reduction of PAF acetylhydrolase activity in active SLE might be due at least in part to a carrier defect related to the activity of the disease. In addition, experiments in which serum of patients with active SLE and serum of healthy subjects were mixed in different combinations indicated the absence of factors inhibiting PAF acetylhydrolase activity in SLE patients. | |
| 2525983 | Etodolac, a new nonsteroidal anti-inflammatory drug: gastrointestinal microbleeding and en | 1989 Mar | A review of the literature is presented on the gastrointestinal effects of etodolac, a new nonsteroidal anti-inflammatory drug (NSAID), as evaluated in both microbleeding and endoscopic studies. In four microbleeding studies, gastrointestinal blood loss in healthy subjects was estimated by a 51Cr-erythrocyte labeling method before drug treatment, after 7 days of treatment with NSAIDs including etodolac, and 1 week after the last day of treatment. In these 7-day studies, the gastrointestinal blood loss seen with etodolac (600 to 1200 mg/day) was similar to that seen with placebo and significantly (p less than 0.05) less than that seen with aspirin (2600 mg/day), naproxen (750 mg/day), ibuprofen (2400 mg/day), or indomethacin (200 mg/day). Naproxen, ibuprofen, and indomethacin caused mean daily blood losses in excess of 1 ml/day over baseline values. The increase with aspirin was 4 to 5 ml/day. In contrast, the greatest mean daily increase in blood loss with etodolac therapy was 0.2 ml. In a 4-week study of etodolac (600 and 1000 mg/day) and piroxicam (20 mg/day) given to patients with osteoarthritis or rheumatoid arthritis, blood loss seen with etodolac was comparable to that seen with placebo and significantly less than that seen with piroxicam. Gastrointestinal irritation was also assessed by endoscopy after 1 week of NSAID or placebo treatment. Endoscopy scores after etodolac treatment (up to 1200 mg/day) were similar to scores at baseline and after placebo and were significantly lower than scores following treatment with aspirin (3900 mg/day), indomethacin (200 mg/day), ibuprofen (2400 mg/day), or naproxen (100 mg/day). The effects of etodolac (600 or 1000 mg/day) and diclofenac (150 mg/day) were not different from each other or from baseline. These data indicate that etodolac, in these studies, did not cause clinically significant gastrointestinal microbleeding or visible gastric injury. By the criteria used in these studies, etodolac is less irritating to the gastrointestinal tract than aspirin, indomethacin, ibuprofen, naproxen, or piroxicam, and compares favorably with diclofenac. |