Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 6334356 | Specificity of plasma cells in the rheumatoid synovium. I. Immunoglobulin class of antiglo | 1984 Oct | Plasma cells synthesizing rheumatoid factors (RF) were identified by fluorescent staining of sections of synovium and macrophage-depleted cells from dispersed synovial tissue. The latter avoided problems related to sampling errors in studying tissue sections and in the uncertainty raised by the staining of macrophages with intracellular complexes. Plasma cells producing IgG predominated, and seropositive patients had a higher proportion of IgM producers than seronegative subjects. None the less, in both groups of patients more than 90% of the IgM plasma cells were synthesizing RF, whereas the corresponding figure for IgG was between 50% and 60%. Only around 10% of IgA plasma cells were positive for RF. The high percentage of IgM plasma cells making RF would tend to argue for an IgG-specific response and against direct polyclonal activation as the stimulus. The percentage of IgG-producing cells positive for RF is also consistent with a dominant response to IgG. Accepting the difference in the relative proportion of total IgM- to IgG-producing plasma cells in seropositive as against seronegative patients, the close similarity between the two groups in the fraction of cells making RF favours the view that the two groups have a comparable underlying immunopathology dependent on IgG autosensitization. From the technical standpoint, the dispersed cell method gives results in line with those obtained with sections but which are easier to read, whereas the fluorescent techniques described give clear and reproducible results for the detection of RF of different heavy-chain isotype. | |
| 6413684 | II. Unbound versus total serum gold concentration: pharmacological actions on cellular fun | 1983 Aug | Unbound serum gold (UBSG) has received little attention, possibly because of rapid in vivo decay and in vivo concentration below the range of existing analytical procedures. We have recently developed a methodology enabling quantitation and study of UBSG during chrysotherapy to assess effects on cellular functions. UBSG after gold administration is labile, declining rapidly after attaining peak values at which lymphocyte mitogen response and polymorphonuclear phagocytosis were observed to be suppressed. Oral gold, i.e., auranofin, 3 mg BID as compared to systemic chrysotherapy 50 mg/wk, resulted in a higher percentage of UBSG to total serum gold. | |
| 6993671 | Gastrointestinal microbleeding: comparisons between benoxaprofen and other nonsteroidal an | 1980 | Unlike other nonsteroidal antiinflammatory agents, benoxaprofen has only minor antiprostaglandin synthetase activity. This property may explain the lack of gastric irritation seen in animal studies. To evaluate gastric irritation in man, benoxaprofen was compared with aspirin, naproxen, ibuprofen, sulindac, and indomethacin by measuring fecal blood loss with chromium-51 tagged red blood cells in randomized double-blind crossover and parallel studies. Benoxaprofen produced significantly less blood loss than aspirin, naproxen, or indomethacin, and less blood loss than ibuprofen or sulindac. Benoxaprofen also caused the fewest gastrointestinal complaints. | |
| 6221399 | Healthy and diseased striated muscle studied by analytical scanning electron microscopy wi | 1982 | X-ray microanalytical investigations of striated muscles in the scanning electron microscope are reviewed. The main part of the studies was performed on cryosections cut with a conventional cryostat operating at -20 degrees C to -40 degrees C. The preparation procedure including different types of attachment of the sections to the specimen holder is described in detail. The elemental changes in muscle are related to the muscle fibre type as demonstrated by histochemical methods or to histochemically demonstrated inclusions in diseased muscles. This is of great importance, because muscle disorders are often characterised by selective involvement of different muscle fibre types. The preparation methods of muscle for analytical scanning electron microscopy and the obtained results are compared with studies performed on thin cryo and epoxy sections, analysed in the transmission and scanning-transmission electron microscope. It is evident that X-ray microanalysis performed on thick cryosections provide a quick survey of the elemental composition of whole cells, and should be followed in interesting cases by close examination on the organelle level studied in thin cryosections in the transmission and scanning-transmission electron microscope. | |
| 527254 | Circulating immune complexes in IgA deficiency. | 1979 Oct | Circulating immune complexes (IC) were demonstrated in patients with serum IgA deficiency. Sixteen of thirty-one IgA deficient patients had serum IC detected by solid phase C1q radioimmunoassay for IgG class complexes. The presence of cryoglobulins (thirteen out of thirty-one patients) and increased polyethylene glycol precipitation (ten out of thirty patients) provided additional evidence for the presence of IC. Fourteen patients were asymptomatic but seven had clinical evidence of disease which could have been IC mediated: two with glomerulonephritis, three with polyarthritis, one with vasculitis and one with thyroiditis. Serum IC remained detectable in multiple samples over several months but this correlated poorly with the presence or absence of disease. Serum antibody to IgA was detected in fifteen out of thirty-one patients. There was no direct relationship between the presence of IC and the level of serum anti-IgA antibody; however, this antibody was shown to be present in the IC isolate in eight patients. It is proposed that a considerable portion of the IC load in IgA deficiency results from defective antigen exclusion at the level of the mucosa. | |
| 6509799 | Circulating immune complexes (CIC), carcinoembryonic antigen (CEA) and CIC containing CEA | 1984 Dec | It has been suggested that circulating immune complexes (CIC) would provide a useful tumour marker system and that carcinoembryonic antigen (CEA) may form an antigen component of CIC found in patients with colorectal cancer. In this study the clinical usefulness of CIC and CIC containing CEA (CEA-IC) was investigated. Concentrations of CIC were measured in 30 patients with colorectal cancer. Fourteen patients were studied sequentially at approximately 1 month intervals after apparent curative resection of the primary tumour. Results were correlated with those obtained from serum CEA and compared to clinical status. CEA-IC were measured using a novel assay and compared with CIC and CEA values in 29 patients. CIC concentrations were elevated in patients with known disease and predicted clinical relapse in four of 14 patients. In two patients CIC remained elevated despite sustained remission. CEA-IC were not detectable in any of the patients studied. CIC estimations may augment CEA measurements as indicators of disease recurrence but lack of specificity makes them of little practical value as tumour markers in colorectal cancer. No evidence was found to support previous reports that CEA was an antigen component of CIC in this disease. | |
| 228187 | Effects of D-penicillamine on neuromuscular transmission in rats. | 1979 May | Treatment of patients with D-penicillamine (D-P) has been associated with a syndrome similar to myasthenia gravis (MG). To explore this association, we examined the effects of D-P on neuromuscular transmission in rat muscle. In the first experiment, bath-applied D-P had no significant effect on either miniature endplate potential (MEPP) amplitude or action potential (AP) amplitude. Endplate potential (EPP) amplitude and spontaneous MEPP frequency decreased significantly at concentrations approximately 40 times the maximum human therapeutic level. In the second experiment, rats receiving D-P by daily injections for 33 to 37 days did not differ from controls in any of the measured electrophysiologic characteristics. Electron microscopy of muscle endplates from rats treated with D-P showed no evidence of degeneration or simplification. In all cases, thymus histology by light microscopy was normal, and no antireceptor antibodies were found. Thus, D-P has a mild direct presynaptic effect on neuromuscular transmission at high concentrations, but this effect is too small to account for the weakness seen in the myasthenia-like syndrome in humans. | |
| 3903373 | Clinical utility of assays for circulating immune complexes. | 1985 Jul | There are now many assays for the quantification of circulating immune complexes, each with distinct specificity and sensitivity. In a wide variety of rheumatic, infectious, neoplastic, and metabolic conditions, levels of circulating immune complexes may be elevated. In select situations, determination of circulating immune complex levels may help clinicians in the management of their patients. In lupus erythematosus, circulating immune complex levels, in conjunction with other immune parameters, may provide more insight into the disease course and activity than assessment of end organ parameters alone. In the differential diagnosis of infective endocarditis, serial levels of circulating immune complexes may provide evidence of effectiveness or failure of treatment. There is evidence that assays for circulating immune complexes may be of potential benefit in the management of Lyme disease and acute myelogenous leukemia. | |
| 808125 | Thrombocytopenia associated with gold therapy. Observations on the mechanism of platelet d | 1975 Aug | Severe thrombocytopenia developed in a patient with rheumatoid arthritis during gold therapy. Increased numbers of marrow megakaryocytes, shortened 51Cr-labeled platelet survival and platelet phagocytosis by splenic macrophages indicated that thrombocytopenia was due to excessive platelet destruction. Aurothiomalate disodium antigenicity was demonstrated by increased lymphocyte blastogenesis, and accentuation of blood and splenic leukocyte migration in the presence of the gold salt. In vitro splenic immunoglobulin G (IgG) production was markedly increased, and a significant portion of the culture-produced IgG attached specifically to homologous platelets and platelet membranes. Serum antiplatelet antibodies could not be demonstrated, nor could it be shown that gold enhanced the binding of splenic-synthesized IgG to platelets. The data indicate an immunologic mechanism for gold-associated thrombocytopenia and permit speculation as to possible ways in which unidentified antigens may be involved in the pathogenesis in idiopathic thrombocytopenic purpura. | |
| 6976356 | Production of antibodies specific for Fc, Fab', and streptokinase-streptodornase in vitro | 1982 Jan | To study antibody (Ab) biosynthesis in rheumatoid arthritis (RA), the immunoglobulin (Ig)M anti-Fc, anti-Fab', and antistreptokinase-streptodornase (SKSD) produced by peripheral blood lymphocytes (PBL) were measured at intervals from 1 to 19 d in culture. PBL from 17 seropositive patients with active RA and 30 age-matched controls were evaluated. Within the first 24 h, PBL from six of eight patients released >30 ng IgM anti-Fc, even in the absence of pokeweed mitogen (PWM). This early release of Ab was blocked by cycloheximide. With or without PWM, PBL from normal donors did not release IgM anti-Fc until after 3-5 d in vitro. By day 9, unstimulated PBL from seven patients made > 100 ng IgM anti-Fc. Un-stimulated PBL from normals never made >95 ng of this Ab. When PWM was added, PBL from normal donors released as much IgM anti-Fc as was found in RA donor cultures. Paradoxically, addition of PWM to PBL of RA patients suppressed release of IgM anti-Fc in 4 of 17 cases to levels significantly below those found in unstimulated cultures of the same cells. Without PWM, PBL from RA donors frequently failed to make IgM anti-SKSD (P < 0.05 compared with normal donors' cells). With PWM, the quantities of IgM anti-SKSD released were comparable. Fluctuations in IgM anti-Fab' levels during the life-time of these cultures were sufficient to suggest that these Ab may be taken up in immune complexes. This hypothesis was verified by acidifying (pH 3.1) culture supernatants to which (125)I-Fab' had been added previously. The samples were then neutralized (pH 7.6) and 12% polyethylene glycol was added to separate free from antibody-bound (125)I-Fab'. This procedure increased the quantity of (125)I-Fab' precipitated by > 10-fold in some cases. These studies suggest that there are a variety of abnormalities in Ab biosynthesis in RA. These include spontaneous synthesis of comparatively large quantities of IgM anti-Fc, relatively suppressed release of IgM anti-SKSD, and a paradoxical reduction, in some cases, in the biosynthesis of IgM anti-Fc after addition of PWM. | |
| 6086752 | Activated T cells in vivo and in vitro: divergence in expression of Tac and Ia antigens in | 1984 Sep | Elevated numbers of non-blastoid T cells expressing either the Tac or Ia antigens were found on separate cell populations in inflammatory synovial tissues and fluids of individuals with arthritis. Those synovial T cell preparations containing Tac+ cells exhibited marked proliferation upon the addition of IL 2 without concomitant mitogen stimulation; T cell eluates containing Ia+ but not Tac+ T cells did not show significantly increased levels of blastogenesis. Paired T cell preparations from blood had only minor increases in the number of Tac+ T cells and moderate increases in the number of Ia+ cells. The blood cells did not exhibit significant proliferation to IL 2. In contrast mitogen or allogeneic activation of T cells induced blastoid cells that expressed abundant per cell amount of Ia or Tac antigens. These blastoid cells resembled the small T cells of inflammation in having only very limited overlap between the population that bore Ia antigens and those with the Tac antigen; however, there was a preponderance of Tac-bearing cells. | |
| 300245 | Psoriatic arthritis and anti-nuclear factor. | 1977 Jan | Positive tests for anti-nuclear factor were found in 7% of 101 patients with psoriatic arthritis. In only one case was this at a significantly high titre. The overall prevalence is that expected in the community, though there was a high prevalence in those with Sjögren's syndrome. This is a further differentiating feature from rheumatoid arthritis. | |
| 805916 | [Transfer factor. Properties and possible therapeutic applications (author's transl)]. | 1975 Mar 28 | Transfer factor (TF) is a dialysable and ultrafilterable extract from human leukocytes. It contains only substances with a molecular weight of less than 10 000. Several biological activities of TF are so far known. These refer to the transfer of specific cellular immunity from one individual to another and a stimulating effect, probably of an unspecific nature, on the cellular immune system. So far, favorable therapeutic results have been obtained in chronic candidiasis and a few other chronic infectious diseases, in the Wiskott-Aldrich syndrome and possibly also in some special malignant tumors. The small number of treatments does not permit any firm conclusions to be drawn. | |
| 6810502 | Screening study on excretion pattern of urinary glycosaminoglycans from orthopedic patient | 1982 Jun | To obtain a clue for the metabolic disorder of glycosaminoglycans (GAG) in orthopedic diseases, a screening study on excretion pattern of urinary GAG from orthopedic patients was performed by the procedures of Nagatsuka et al. (1980). All the urines examined gave three regular GAG-bands. Besides the regular bands, some samples gave irregular bands. Of 123 cases examined in the present study, the numbers of cases with an abnormal excretion pattern of urinary GAG in the regular bands (A) and with the irregular band(s) (B) were as follows: 23(A) and 7(B) in 38 cases of rheumatoid arthritis (RA); 8(A) and 5(B) in 13 cases of malignant bone tumor; 11(A) and 3(B) in 12 cases of benign bone tumor; 16(A) and 3(B) in 25 cases of bone metabolic and connective tissue diseases; 6(A) and 4(B) in 9 cases of osteaorthritis; 6(A) and 3(B) in 8 cases of spine diseases; and 14(A) and 8(B) in 18 cases of other orthopedic diseases. The excretion patterns of urinary GAG suggested that the metabolic rates of chondroitin sulfates tended to elevate in most cases of (A). Also, certain metabolic disorder of dermatan sulfate and heparan sulfate was suggested in several cases of (A). In addition, the abnormal metabolism of acidic glycoprotein(s) was suggested in many cases of (B). Excretion of a large amount of dermatan sulfate was elucidated in one case (Case 20 of bone metabolic and connective tissue diseases) by digestion with chondroitinases after the screening study. Therefore, the metabolic disorder of dermatan sulfate was indicated in this patient. The low activity of alpha-L-iduronidase in her urine supported this indication. This patient was finally diagnosed as mucopolysaccharidosis I-S (Scheie syndrome). | |
| 4573789 | Indirect cutaneous immunofluorescence. II. Clinical significance. | 1973 Apr | Sera of 532 patients with bullous diseases, connective tissue diseases and malignancies were tested for pemphigus epidermal intercellular fluorescence (ICF) and for the bullous pemphigoid ;tubular' band by the indirect fluorescent antibody technique. Human normal skin cryostat sections were used. The band and ICF were seen primarily only in bullous pemphigoid and pemphigus respectively, Some indirect band and ICF-negative patients demonstrated positive direct results in involved skin. suggesting that direct tests should be performed in indirect negative patients clinically thought to have pemphigus or bullous pemphigoid. No close correlation was found between disease activity and positive or negative indirect tests in bullous pemphigoid and pemphigus. Steroids did not interfere with positive results of this diagnostically extremely valuable test. | |
| 125344 | Studies on the nature of circulating DNA in systemic lupus erythematosus (SLE). | 1975 Jun | The isolation and purification of DNA from the sera of patients with SLE is described. Buoyant density determinations of this DNA using CsCl gradients suggest in some cases that it may be of endogenous origin. DNA from the synovial fluid of an SLE patient with septic arthritis was also shown to have a buoyant density of human DNA as well as being of considerable size variation. In addition, this synovial fluid contained antibody to DNA and evidence of DNA:anti-DNA complexes, suggesting that immune complexes composed of human DNA and antibody may be involved in the pathogenesis of the arthritis. Also described are preliminary experiments characterizing the conformation of the DNA present in DNA:anti-DNA immune complexes. | |
| 1099959 | Physiologic and pharmacologic alterations of rat leukocyte chemotaxis (Cx) in vivo. | 1975 Jun 13 | The method of adoptively transferring 51Cr-labeled rat leukocytes iv to isologous recipients was used to quantitate the extravascular accumulation of specific cell types at the site of inflammation induced by local injection of various phlogistic agents. Experiments were designed to determine whether cellular accumulation could be modified at the level of the chemotactic factor, by serum components, or by alteration of the responding cell itself. The results indicated a selective attraction of mononuclear cells to the local injection site of BCG and of neutrophils to the injection site of aggregated but not monometric gamma-globulin. Thus, leukocytic accumulation was found to be dependent upon the local generation of specific reactants that were particular to the agent employed. Leukocytic accumulation could also be modified by serum factors. Cellular accumulation was inhibited when leukocytes were exposed to serum that contained phagocytosable particles or after phagocytosis in vitro prior to adoptive transfer. Chemotaxis of lymphocytes could be induced by their preincubation with sera from adjuvant arthritic animals. These observations were confirmed by in vitro studies and by the finding that 6 days after adjuvant injection , lymphocytes but not mononuclear cells accumulated at the noninjected extremity. In the final series of experiments, it was shown that BCG immunization was capable of inducing a unique population of peritoneal mononuclear cells that after adoptive transfer had an enhanced capacity to remain in the circulation, which, in turn, resulted in a functional increase in their accumulation at an inflammatory reaction site. In conclusion, these studies indicated that the chemotactic activity of adoptively transferred cells can be modified by changes in the chemotactic stimuli, can be enhanced or depressed by serum factors, and is a function of the physiologic capability of the cell population employed. | |
| 807730 | Heterogeneity of IgM/IgG cryocomplexes: immunological-clinical correlation. | 1975 Jun | A detailed study has been made of the mixed cryoglobulins (MCs) occurring in four patients with different disease states. These included (1) macroglobulinemia of Waldenström with an IgM(K)/IgG cryocomplex containing Clq, free DNA, rheumatoid factor, anti-ssDNA and VDRL activity; (2) Peetom-Meltzer syndrome with an IgM(K)/IgG cryocomplex containing free DNA, Clq, Cls, fibrinogen, alpha2-macroglobulin and beta-lipoprotein; (3) rheumatoid arthritis with an IgM(K)/IgG cryocomplex containing rheumatoid factor, free DNA and anti-ssDNA activity; and (4) angioimmunoblastic lymphadenopathy with an IgM(K)/IgG cryocomplex containing rheumatoid factor, free DNA and anti-I cold agglutinin activity. All of these patients exhibited multisystem involvement with evidence of vascular injury. A review of the MCs found in various clinical states, reveals that whereas in systemic lupus erythematosus MCs almost invariably possess antinuclear factor activity and contain DNA as well as some components of complement, in Peetom-Meltzer syndrome MCs do not have these characteristics, but invariably have strong rheumatoid factor activity, usually absent in MCs from systemic lupus erythematosus. MCs in lymphoproliferative disorders have strong rheumatoid factor activity but not ANF activity. In infectious diseases, MCs usually exhibit strong rheumatoid factor, VDRL and cold agglutinin activity, and co-precipitate with alpha2-macroglobulin. While there is some overlap in the characteristics of MCs from various clinical diseases, the above mentioned differences are probably of some biological importance and require further investigation. | |
| 4042425 | Serum from patients with pernicious anaemia blocks gastrin stimulation of acid secretion b | 1985 Aug | We examined 51 sera from patients with pernicious anaemia for their capacity to block maximal gastrin stimulation of acid secretion by isolated rodent gastric parietal cells. 14C-aminopyrine accumulation was used as the index of acid secretion in vitro. Sera from patients with pernicious anaemia gave significantly (P less than 0.005) more block of maximal gastrin stimulation of acid secretion (61.7 +/- 37.8%) than sera from 10 patients with systemic lupus erythematosus (19.6 +/- 17.7%), 10 with scleroderma (34.2 +/- 22.3%), five with rheumatoid arthritis (22.4 +/- 15.6%) or 30 from healthy persons (27.4 +/- 12.8%). Maximal histamine stimulation of acid secretion was not inhibited. The blocking factor was present in serum IgG fractions, and serum and IgG fractions gave parallel dose-response and dilution curves. The serum block was abolished by absorption with gastric mucosal cells and correlated with the presence of parietal cell surface autoantibody. We conclude that serum immunoglobulin in pernicious anaemia can block gastrin stimulation of acid secretion and suggest that this block may be mediated by competition with gastrin for surface receptors on parietal cells. | |
| 405403 | Serum folates in man. | 1977 May | In an aseptic microbiological assay of folate compounds and their breakdown compounds, using Lactobacillus casei, Streptococcus faecalis, and Pediococcus cerevisiae, 4a-hydroxy-5methyl-4,5,6,7-tetrahydrofolate and 5-methyl-5,8-dihydrofolate were inactive under all conditions to all three organisms and 5-methyl-5,6-dihydrofolate was inactive unless ascorbate was present in the incubation medium, and then only to L. casei. 5-Methyltetrahydrofolate was active only for L. casei, and activity in purified samples to S. faecalis was due to trace amounts of folic acid. Analysis of S. faecalis values in the serum in normal subjects and in patients with various disorders showed that levels of 10-formyltetrahydrofolate are raised in coeliac disease, leukaemia, rheumatoid arthritis, and schizophrenia. 5-Methyltetrahydrofolate is readily absorbed by normal human subjects and by patients with pernicious anaemia but poorly absorbed by patients with coeliac disease or leukaemia. 5-Methyl-5,6-dihydrofolate was quickly absorbed by normal human subjects, being reflected by a considerably raised level of 5-methyltetrahydrofolate in serum when sodium bicarbonate was given by mouth before the 5-methyl-5,6-dihydrofolate. These higher levels were comparable to those in patients with pernicious anaemia after oral administration of 5-methyl-5,6-dihydrofolate. Oral 5-methyl-5,8-dihydrofolate and 4a-hydroxy-5-methyl-tetrahydrofolate did not appear as microbiologically active folates in the serum. The findings of this study suggest that the availability for biological utilisation of the major dietary folate compounds will depend on the amount of gastric acidity and of ascorbate in the intestinal chyme. Many may be unavailable for metabolic utilization in the body. |