Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 6693375 | Mechanism of selenium-glutathione peroxidase and its inhibition by mercaptocarboxylic acid | 1984 Jan 25 | In a systematic search for effectors of glutathione peroxidase, a number of mercaptocarboxylic acids and tertiary mercaptans were found to be strong and specific inhibitors of the enzyme glutathione peroxidase. Assessment of various models was made by linear and nonlinear least squares fitting techniques. The results support the formation of reversible enzyme-inhibitor complexes. The active site selenium is trapped by the rapid binding of the inhibitor in competition with GSH. Data are consistent with the formation of thioselenenate adducts of the active site. The kinetic model which best describes the observed inhibition by the very strong inhibitor mercaptosuccinate implies that a selenenic acid with a kinetically significant lifetime is not formed when hydroperoxide is reduced. A noncovalent binding site for GSH or the presence of a cysteine residue at the active site of the enzyme provides a mechanistic rationale for the observed kinetics. Three of the most potent inhibitors found in this study, mercaptosuccinate, penicillamine, and alpha-mercaptopropionylglycine, are currently used as slow-acting drugs in the treatment of rheumatoid arthritis. Overall, the evidence suggests that glutathione peroxidase may be involved in the etiology of this disease. | |
| 6870202 | Myasthenia gravis in children: long-term follow-up. | 1983 May | We report observations made on 149 patients with juvenile myasthenia gravis studied from onset of disease for as long as 40 years. Median follow-up was 17 years; minimum was 4 years. Eight other patients with congenital myasthenia gravis were studied separately. Of the juvenile myasthenic patients, 85 (57%) underwent thymectomy because of diseases severity. In juvenile myasthenia gravis, a spontaneous remission rate of 22.4 per 1,000 person-years was observed, regardless of disease duration. A remission rate of 260 per 1,000 person-years was seen during the first year after thymectomy, with a rate of 95 per 1,000 person-years during the next 2 years. Early surgery, presence of bulbar symptoms, absence of ocular signs or generalized symptoms, onset of symptoms between ages 12 and 16, and presence of other immune disease were associated with increased postoperative remission rates. Epilepsy (4 patients) and neoplasia (7 patients) were the most frequent associated nonimmune disorders; rheumatoid arthritis (5 patients), juvenile-onset diabetes mellitus (3 patients), asthma (3 patients), and thyroid disease (3 patients) were the most frequent associated immune diseases. | |
| 6112603 | Primary biliary cirrhosis--a revised clinical spectrum. | 1981 Jun 13 | The presentation or method of detection of 93 patients with primary biliary cirrhosis (PBC) from Northern England is reported. Almost half (45/93) the patients had no symptoms of liver disease when PBC was diagnosed; in many of them serum antimitochondrial activity (AMA) was detected during immunological screening for other diseases. 13 patients with normal liver function tests had symptomless PBC. Liver histology in 6 of these was diagnostic for PBC, and 7 had histology suggestive of PBC; all had a positive AMA titre greater than or equal to 1/40. The mortality of the symptom-free AMA-positive patients over a mean follow-up of 4-5 years did not differ from that of the general population. Only 1 out of 45 initially symptom-free patients died in the follow-up period (8 months-12 years). 37 patients had disorders which may be associated with PBC--including 16 with thyroid disease, 9 with rheumatoid arthritis, and 5 with mixed connective tissue disease. It is suggest that, as with autoimmune thyroid disease, overt organ damage never develops in many patients with symptomless PBC. | |
| 12310237 | Evaluating the pill. | 1981 Spring | ||
| 316494 | The nutritional regulation of T lymphocyte function. | 1979 Sep | Prostaglandin (PG) E1 plays a major role in the regulation of thymus development and T lymphocyte function and the evidence for this is reviewed. The production of PGE1 is dependent on nutritional factors with linoleic acid, gamma-linolenic acid, pyridoxine, zinc and vitamin C playing key roles. Inadequate intake of any one of these will lead to inadequate PGE1 formation and defective T lymphocyte function. Megadoses of any one are likely to be only minimally effective in the absence of adequate intakes of the others. By careful attention to diet it should be possible to activate T lymphocyte function in the large number of diseases including rheumatoid arthritis, various auto-immune diseases, multiple sclerosis, and cancer in which such function is defective. It is possible that T lymphocytes may require both endogenous and exogenous PGE1 in order to function adequately. It is therefore of particular interest that many cancer cells and virally infected cells are unable to make PGE1 because they cannot convert linoleic acid to gamma-linolenic acid. The direct provision of gamma-linolenic or dihomo-gammalinolenic acids in these situations is worthy of full investigation. | |
| 624591 | Morphological features and functional properties of human fibroblasts exposed to Actinomyc | 1978 Jan | Connective tissue fibroblasts undergo cytopathic degenerative changes during certain long-term inflammatory diseases such as rheumatoid arthritis and periodontitis. The failure of inflamed tissues to repair properly may result from functional alterations of fibroblasts within the affected tissues. Numerous previous studies indicate that direct cytotoxicity by bacterial or other substances may be responsible for the cellular alterations observed in vivo. We have tested this hypothesis by exposing cultures of human diploid fibroblasts to homogenates of Actinomyces viscosus (a microorganism associated with periodontitis and capable of causing other chronic inflammatory diseases) and analyzing the effects on cell viability, morphology, and function. The cells bind and subsequently engulf relatively large quantities of the bacterial substances. These substances do not appear to be toxic to fibroblasts as determined by 51Cr release and microcytotoxicity assays, although there is a slight but significant decrease in protein synthesis (P less than 0.01) as measured by the incorporation of [14C]proline. However, collagen production was not altered, and the cytopathic alterations observed in diseased tissues in vivo did not occur in the exposed cells. These findings suggest that A. viscosus substances do not directly cause injury to connective tissue fibroblasts in periodontal disease but may, through cell-surface binding, mark these cells for subsequent immune-mediated damage. | |
| 300568 | The incidence and clinical significance of antibodies to extractable nuclear antigens. | 1977 Jan | Sera from 378 patients were assayed for antibodies to extractable nuclear antigens (ENA), ribonucleoprotein (RNP) and nonnucleoprotein (Sm). Anti-ENA antibodies were not found in control subjects, patients with rheumatic diseases and negative fluorescent antinuclear antibodies (FANA), or in patients with rheumatoid arthritis, dermatomyositis, drug-induced lupus, idiopathic thrombocytopenic purpura (ITP), or hemolytic anemia with positive FANA. Anti-Sm antibodies were found in 32 per cent of patients with systemic lupus erythematosus (SLE) and were not found in any other condition. There were no significant clinical or serological differences between patients with and without anti-Sm antibodies. Anti-RNP antibodies occurred in 15 per cent of SLE patients, 9 per cent of scleroderma patients, and in 100 per cent of patients with mixed connective tissue disease. SLE patients with anti-RNP antibodies had a significantly lower anti-DNA antibody titer and a significantly lower incidence of nephritis and impaired renal function. Anti-Sm and anti-RNP titers did not vary with changes in clinical status. Awareness of the presence of anti-Sm and anti-RNP antibodies is diagnostically useful. Anti-RNP antibodies have a prognostic value as well. | |
| 2997448 | Some nonsteroidal antiinflammatory drugs inhibit the generation of superoxide anions by ac | 1985 Aug | Representatives of the major classes of nonsteroidal antiinflammatory drugs (NSAID) were assessed for their effects on superoxide anion (O2-.) production by human polymorphonuclear leukocytes stimulated with phorbol myristate acetate or N-formyl methionyl-leucyl phenylalanine (fMLP). Three levels of effects were studied: (1) overall inhibition of O2-. production, (2) the inhibition of interaction between fMLP and specific receptors at the cell surface, and (3) intermediate proenzyme and enzyme effects. Some, but not all drugs inhibited O2-. production. In general, drugs that inhibited O2-. production inhibited fMLP-receptor interactions in a consistent dose dependent fashion, showing noncompetitive kinetics. Drugs that failed to inhibit O2-. production showed weak and variable effects on receptor binding and on the intermediate enzymes. Clinical observations suggest that inflammation in diseases such as gout respond differently to NSAID than diseases such as rheumatoid arthritis; studies of drug effects may help to clarify the differences in pathogenesis of these inflammatory diseases. | |
| 3920862 | Effect of ibuprofen on heterotopic ossification after hip replacement. | 1985 Feb | A double-blind, placebo-controlled study was made of the influence of the anti-inflammatory agent ibuprofen on heterotopic ossification after total hip replacement for arthrosis, fracture or rheumatoid arthritis. Seven drop-outs left 21 patients on medication and 22 on placebo in two comparable groups. Heterotopic ossification appeared in one third of the patients in the ibuprofen group and in three fourths in the control group 12 months after surgery. Five patients in the latter group developed true heterotopic bone, compared to one of the patients on medication. Heterotopic ossification was as common among osteoarthritic patients as among others. There was no difference in the range of motion at 12 months postoperatively between patients with and without heterotopic ossification. In the 22 patients with heterotopic ossification this was demonstrated in all but eight within 6 weeks, and in only three did it appear later than 3 months postoperatively. Five of the six patients who showed heterotopic bone with trabecular structure were male. Since inflammation is a dominant feature in the postoperative phase, the effect of ibuprofen on heterotopic ossification is probably its inhibition of the synthesis of prostaglandins. This implies that prevention is most successful if commenced before or at the time of operation. | |
| 4028976 | Effect of gold on selenium and glutathione peroxidase activities in rat tissues. | 1985 | Gold (Au) thioglucose, used to treat inflammatory diseases such as rheumatoid arthritis, inhibits the selenium (Se)-dependent glutathione peroxidase. The present study examines the ability of Au to act either as a Se antagonist or as a GSH peroxidase inhibitor in vivo. The effects of gold thioglucose loading on Se distribution, and on Se-dependent GSH peroxidase and GSH S-transferase, were examined in rats fed three dietary levels of Se (0, 0.2, and 2.0 ppm), and with or without adjuvant-induced inflammation. Kidney, liver, spleen, testes, and erythrocytes were selected for study based upon their high Se content and their ability to concentrate Au. Au loading increased kidney, liver, and spleen Se concentrations, and this effect was dependent upon dietary Se levels. Rats fed Se-supplemented diets had higher levels of Au in kidney, liver, and spleens than did rats fed a Se-deficient diet. Au loading decreased GSH peroxidase activity in kidney, liver, and erythrocytes. The decrease in GSH peroxidase in kidney and liver, and the increase in Se concentration in these tissues, suggest that Au-Se complexes may have limited the biosynthesis of the enzyme. Au affects Se distribution, and Se concentrates Au in tissues with a high lysosomal content. | |
| 2412349 | Intravenous gammaglobulin therapy in idiopathic thrombocytopenic purpura. Results with the | 1985 | The effect of high-dose intravenous gammaglobulin (IVG) therapy with a CLB preparation was studied in 42 patients: 8 patients had acute and 26 patients had chronic idiopathic thrombocytopenic purpura (ITP); 5 patients had thrombocytopenia accompanied by various diseases such as systemic lupus erythematosus, auto-immune haemolytic anaemia and neutropenia; 3 patients had hypoplastic anaemia and 1 patient had neutropenia and rheumatoid arthritis. After treatment, a rise in platelet count occurred in about 75% of the patients with ITP, although there was no sustained response in any of the patients. There was no correlation between the strength of platelet antibodies as detected by the direct immunofluorescence test before infusion and the pattern of response to the infusion. In most cases of ITP, no immune complexes, as measured by Clq-binding assay, were observed. Furthermore, we found no relationship between the amount of Clq-binding activity of patients' sera and the reaction pattern after infusion of IVG. Splenectomy of the patient had no influence on the outcome of IVG therapy. | |
| 6530002 | Abnormal concentration of stable HbA1 in non-diabetic patients. | 1984 Dec | To study its specificity for hyperglycemia, stable HbA1 was determined with ion-exchange chromatography in 240 patients consecutively hospitalized in the department of internal medicine and in a non-diabetic reference population. Reference values were found to increase significantly with age in the age groups less than 30, 30-60, and greater than 60 years. 41 patients had stable HbA1 more than 2 SD above the mean of the reference group and random blood glucose less than 7 mmol/l, and 21 of these were classified as non-diabetics according to data in medical records. Four non-diabetic patients had stable HbA1 higher than + 4 SD. One of them had haemoglobinopathia, one severe anaemia under cortisone treatment, one cortisone treated myelomatosis with renal insufficiency and severe anaemia, and one patient had lymphoma and renal insufficiency. Nine patients had stable HbA1 between + 3 and 4 SD and diagnoses of coronary heart disease (4), rheumatoid arthritis (2), asthma (1), chronic renal failure (1) and malignant melanoma (1). Five of them were treated with cortisone or diuretics. Four patients had stable HbA1 slightly below the reference range. In summary marked elevation of stable HbA1 due to factors other than diabetes occurred in a few patients with haematological disorders. | |
| 6608422 | Correlation of C3d fixing circulating immune complexes with disease activity and clinical | 1984 Mar | Using anti-C3d as a solid phase reagent, C3d fixing circulating immune complexes (CIC) were detected in sera from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis, membranous nephropathy and IgA nephropathy. Particularly, sera from SLE showed the highest CIC levels and highest incidence of positivity among these diseases. In the 51 serum samples from 48 patients with SLE we studied, the CIC detected by the anti-C3d assay correlated well (P less than 0.01) with the CIC detected by the solid phase C1q assay, but not with those detected by the conglutinin assay. In addition, the CIC detected by the anti-C3d assay correlated more significantly (P less than 0.001) with disease activity, as well as some clinical parameters (serum anti-dsDNA antibodies, CH50 and C3 levels) than CIC detected by the other two assays of SLE sera. The anti-C3d binding materials were found to be of intermediate (8-19S) and small (7S) sizes in a small number of SLE sera which we analysed. | |
| 6229185 | Induction of suppressor cell activity by human pregnancy serum. | 1983 Oct | Third trimester pregnancy serum caused a dose-dependent inhibition of the one-way allogeneic mixed leukocyte reaction (MLR) through an effect that occurred during the first 48 hours of culture. Pregnancy serum also inhibited the mitogenic responsiveness of normal mononuclear leukocytes to concanavalin A (Con A) while the responses to phytohemagglutinin (PHA) and pokeweed mitogen (PWM) were less affected. Preincubation of normal peripheral blood mononuclear cells (PBMC) for 48 hours with 10% pregnancy serum enhanced a suppressor activity transferable with cells. These pregnancy serum-induced effector cells suppressed the MLR only when they were autologous to the responder population (p less than 0.05). The same suppressor cell preparation inhibited the proliferative responses of autologous PBMC to Con A (p less than 0.001) and PWM (p less than 0.05). These data suggest that one or more factors in pregnancy serum can induce or enhance suppressor cell activity in vitro. A comparable increase in suppressor cell activity in vivo may be responsible for blocking maternal rejection of the fetus and for the observed improvement in clinical activity of rheumatoid arthritis during pregnancy. | |
| 6573207 | Cancer and secondary leukemia. | 1983 | Acute myeloid leukemia or one of its variants is being reported with increasing frequency as a second neoplasm in patients being treated for multiple myeloma, Hodgkin's disease, non-Hodgkin's lymphoma and a variety of other primary neoplasms and non-neoplastic diseases. Although many of these patients were treated with both chemotherapy and radiotherapy, many received no radiotherapy at all. Drugs most frequently implicated in the causation of acute leukemia and other second neoplasms are the alkylating agents, procarbazine and the nitrosoureas. The frequency of this syndrome varies from less than 1 per cent to 7 per cent in many reported series of patients. There could develop a reluctance to use cytotoxic agents to treat malignant neoplasms for fear of inducing acute leukemia. Although one has to consider this complication, one should not, however, withhold these drugs from a patient with a neoplasm or other potentially fatal disease in whom such therapy is the treatment of choice. We seem to be faced with the paradox that patients benefiting most from chemotherapy may be at highest risk of suffering its undesirable consequences. Although the risk of leukemogenesis or carcinogenesis in man may be small, these drugs should be used with caution in patients with indolent non-neoplastic diseases such as rheumatoid arthritis. | |
| 7126780 | Variations in the relative proportions of microheterogeneous forms of plasma glycoproteins | 1982 Mar | Using lectin affinity crossed immunoelectrophoresis with concanavalin A in the first dimension and electroendosmotic elution with sugar in the second dimension, the microheterogeneity of a range of plasma proteins was examined. Of the five chosen proteins, alpha 1-protease inhibitor and caeruloplasmin displayed complex patterns, with more than four components. Alpha 1-Antichymotrypsin was composed of three or four components whilst alpha 1-acid glycoprotein and alpha 2-HS glycoprotein displayed two, three or four components. The number of components seen in these proteins depended on the serum sample origin. In pregnancy and in patients receiving exogenous aestrogen the relative proportions of the components of all five proteins were altered in the direction of less con A binding; however alpha 1-acid glycoprotein and alpha 1-antichymotrypsin showed the greater change. In acute disorders the proportions of protein components of alpha 1-antichymotrypsin and alpha 1-acid glycoprotein were altered towards a higher level of con A binding components. There is no significant alteration in con A binding associated with the chronic inflammatory response to cancer and rheumatoid arthritis. There was a general reduction of con A binding in all five plasma proteins in conditions when there was a high blood aestrogen level. This decreased affinity for con A was independent of the overall effect of the aestrogen on the serum concentration of the plasma protein. These results suggest that the glycosylation of plasma proteins is probably under the same regulatory system. | |
| 6780154 | Inhibition of active bone resorption by copper. | 1981 | An investigation of the role of copper in bone metabolism was undertaken. Explanted calvaria from 6-day-old mice were grown for 48 h in medium with and without the addition of copper sulfate. Active resorption was found to be significantly inhibited in the presence of copper sulfate concentrations of 10(-6)M and above. Copper sulfate concentrations of 10(-5)M and above inhibited hydroxyproline, protein, and DNA synthesis. Lower concentrations wee ineffective. The effect of 5 X 10(-6)M copper sulfate on resorption was reversible. Several other compounds were tested for similar effects and at 5 X 10(-6)M were found to inhibit bone resorption in the order: copper sulfate greater than brown gold chloride greater than sodium aurothiomalate greater than zinc sulfate greater than sodium sulfate. The copper sulfate effect was twice that of sodium aurothiomalate, and sodium sulfate was not significantly inhibitory. The results suggest that the high serum copper levels associated with rheumatoid arthritis may reflect the activity of a hypothetical control mechanism of bone resorption. In the diseased state this would act to restore the normal rate of bone resorption. | |
| 34757 | [Necrotizing angiitis of small vessels. A clinical study of 25 patients with skin biopsy ( | 1979 Feb 25 | Necrotizing angiitis or vasculitis exhibits a wide clinical spectrum characterized by many different cutaneous manifestations. Diagnosis must be confirmed by histopathology. We studied in retrospect 25 patients whose conditions had been diagnosed by skin biopsy. Histologic examination revealed infiltration by polynuclear cells and fibrinoid necrosis of the walls of the blood vessels in the skin. The great variety of clinical manifestations and etiologies stands out in a review of the records of these patients. Necrotizing angiitis has been found associated with mixed cryoglobulinemia; administration of drugs, milliary tuberculosis, bacterial meningitis, rickettsiosis, staphylococcal sepsis, pharyngotonsillitis, and rheumatoid arthritis. Necrotizing angiitis is a group of diseases with a great variety of clinical manifestations, ranging from benign to fatal. The various entities described to date have been more like different clinical forms of the same disease that distinct conditions. In cases of necrotizing angiitis caused by basically immunological mechanisms, the walls of the blood vessels may be impaired in varying diffuse degrees. The prognosis of the disease depends on the intensity of the inflammation and its repercussions on the parenchymas of different organs. The kidney is the most susceptible organ in this case. Treatment should be directed toward the avoidance of predisposing and etiologic factors, detection of the immunological reaction, requiring careful and individual attention in every case. | |
| 359253 | Relationship of plasma salicylate levels to pain relief with two different salicylates. | 1978 | In a preliminary open study of salsalate (3 g daily for 4 weeks) in 61 patients with rheumatoid arthritis or osteoarthrosis, it was found that although the drug produced satisfactory analgesia in 64% of patients, the incidence of side-effects was high (57% of patients): most were symptoms of salicylism and probably related to the high plasma salicylate levels achieved. In a second open study, 20 patients with osteoarthrosis were treated for 4 weeks with 250 mg diflunisal twice daily and then crossed over to salsalate (3 g daily) for a further 2 weeks. The results of subjective assessments of pain relief showed that both drugs produced satisfactory analgesia, and neither was associated with a significant level of gastro-intestinal bleeding. During the diflunisal treatment period there were no reports of salicylism, and plasma salicylate levels were very much lower than those measured after salsalate. The pain relieving effects of both drugs, assessed from patient preference for one or the other treatment, were unrelated to the plasma salicylate levels and it is suggested that plasma levels may have more relationship to the incidence of side-effects than with therapeutic effects. | |
| 932231 | Biopterin derivatives in human body fluids and tissues. | 1976 May | Levels of biopterin derivatives in urine, serum, milk, cerebrospinal fluid, brain, and liver have been measured with the Crithidia fasciculata assay. Normal levels in serum and urine have been given and compared with those in a number of benign and malignant proliferative disorders, phenylketonuria, kidney disease, Parkinson's disease, schizophrenia, controlled epilepsy, rheumatoid arthritis, and pernicious anaemia. The active component of Crithidia factor in serum was 7,8-dihydrobiopterin. Tissue, urine, and some serum samples contained two active materials, the principal one being 7,8-dihydrobiopterin; a minor constituent was probably tetrahydrobiopterin. Serum biopterin levels following methotrexate administration were raised and subsequent administration of folic acid and 5-formyltetrahydrofolic acid further increased serum levels of biopterin derivatives; this was in contrast to the total absence of response to oral folates without prior methotrexate and to 5-methyltetrahydrofolic acid either with or without methotrexate being given. |