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

ID PMID Title PublicationDate abstract
49034 Amyloidosis: a rational approach to diagnosis by intraoral biopsy. 1975 Jun Amyloidosis and its oral manifestations are briefly described. The techniques for antemortem tissue diagnosis of amyloidosis are reviewed and evaluated. In screening for amyloidosis, biopsy of specific oral lesions (when present) is recommended instead of the traditional biopsy of normal-appearing gingiva. This approach is illustrated with four cases. Although rectal biopsy is generally accepted as the screening technique of choice, it is suggested that intraoral biopsy be considered as an easier, safer, more comfortable, and possibly more fruitful technique. It is advocated that in cases of both documented and suspected amyloidosis both intraoral and rectal biopsies should be performed in order to help provide documentation of the most useful technique for routine screening.
4856589 Latex agglutination test for detection of Australia antigen (HB-Ag) among blood donors and 1974 Jan The application of the latex test for the detection of Australia antigen (Au-Ag) was investigated. Reagents from two commercial sources were compared with the electrophoresis method with regard to sensitivity and specificity using samples from blood donors, hospital patients, and plasma fractions. Discordant results were further investigated by electron microscopy and radioimmunoassay. Differences were noted in the results between these reagents and the significance of the findings together with suggestions for minimizing false positive results are discussed.
7328566 Suppression of Fc Receptor and C4.C3 receptors of the granulocytes from patients with syst 1981 Nov The suppressive functions of Fc receptor and complement (C4.C3) receptors were studied in the granulocytes from patients with systemic lupus erythematosus (SLE). The inhibition of complement receptors was mainly due to immune complex bearing C4 or C3 fragments and to complement fragments in part, because 1. the inhibitory activity was present mostly in macromolecular fraction of SLE serum on gel filtration, and 2. the inhibitory activity was precipitated by 4% polyethylene glycol. The suppression of the complement receptors correlated with SLE disease activity.
968338 The effects of antacids on enteric-coated salicylate preparations. 1976 Aug A volunteer study was undertaken in which the effect of the co-administration of therapeutic doses of aluminium hydroxide and magnesium trisilicate on the excretion of aspirin derived from enteric-coated preparations was studied. A significant alteration in the pattern of salicylate excretion was seen, but the mechanism of the interaction cannot be deduced from the present study. It was concluded that the interaction was of potential therapeutic importance, and further studies based on this pilot investigation have been initiated.
1163 Properties of beta-glucuronidase activity in human synovial fluid. 1975 Dec 15 The purpose of the present study was to evaluate the properties of beta-glucuronidase (EC 3.2.1.31) in human synovial fluid. It was shown to have a pH requirement of 5.0 and a KM value of about 8.0 - 10(-3) M using phenolphthalein beta-glucuronide as the substrate. At low substrate concentration an endogenous inhibitor is demonstrable. The inhibition is of the competitive type and is removed by proteolytic digestion of synovial fluid, whereas hyaluronidase digestion and addition either of Triton X-100 or of various salts to the assay mixture, are ineffective. The possibility that the inhibitor is a protein from serum is discussed.
4821038 Fine-needle aspiration biopsy of spleen in diagnosis of generalized amyloidosis. 1974 Apr 6 Fine-needle aspiration biopsy of the spleen was performed on 18 patients shown to have amyloid deposits in other organs and on 17 control patients being investigated for proteinuria. Of the 18 patients with amyloid disease smears of splenic aspirate were positive in all cases, renal biopsy was positive in 16 out of 16 cases, and rectal biopsy was positive in seven out of 11 cases. None of the splenic smears were positive in the 17 control patients and no amyloid was found in the kidney in 15 of these patients on whom renal biopsy was performed. Splenic aspirate biopsy seems to be a simple and safe procedure for the diagnosis of amyloidosis. It is as accurate as renal biopsy and more accurate than rectal biopsy.
6186003 The area of lymphocyte nucleoli (ALN) and its relationship with RNA synthesis in lymphocyt 1982 Jul The area of lymphocyte nucleoli (ALN) is a recently imagined method (Micu et al., 1978) which can detect cytochemically the microscopically visible surface of nucleolar RNA, measurable in mu2. The normal ALN value in peripheral blood is 84.4 +/- 9.2 mu2. Using in vitro cultures of PHA-stimulated lymphocytes obtained from 106 patients with various internal diseases, the authors could demonstrate a relationship between the rate of the lymphocytic RNA biosynthesis and the ALN variations, namely that an RNA hyper- or hyposynthesis is accompanied by an increase or a decrease, respectively, of the ALN.
4065883 Gastrointestinal amyloid deposition in AL (primary or myeloma-associated) and AA (secondar 1985 Dec Gastrointestinal amyloid deposition was investigated in 21 autopsy cases of nonhereditary systemic amyloidosis, 18 of the AL (primary or myeloma-associated) type and three of the AA (secondary) type. Vascular deposition of amyloid, most apparent in the submucosa, was found in all cases. Parenchymal deposition was observed mainly in the muscularis mucosae and muscularis externa in the AL type, and in the lamina propria mucosae in the AA type. Comparison of amyloid deposition in the stomach and rectum revealed no differences for the AA type. In the AL type, however, deposition in the lamina propria mucosae and muscularis mucosae was more frequent and marked in the wall of the stomach than in the rectum. Thus, gastric biopsy would be more valuable than rectal biopsy in the diagnosis of AL amyloidosis.
7396672 Preliminary report on postoperative results of newly designed stable total knee prosthesis 1980 A newly designed stable total knee prosthesis was made for the severely destructed knee. This prosthesis was named the Yoshino total knee prosthesis, and is a non-hinged type prosthesis consisting of a vitallium femoral component and a ultra-high molecular weight polyethylene tibial component. Clinical results of 127 Yoshino total knee arthroplasties showed the following characteristics: 1) good stability, and 2) good mobility. Stability was exceptionally good, and the results were the same as the hinged total knee prosthesis.
6227981 T-cell immunoregulatory functions in rheumatoid arthritis patients. 1983 Oct We have studied the immunoregulatory function of T8+ (suppressor/cytotoxic) and Leu3a+ (inducer/helper) T cells from rheumatoid arthritis (RA) patients by measuring the effect of these T-cell subpopulations on the generation of immunoglobulin-secreting cells by normal allogeneic B cells after stimulation with pokeweed mitogen (PWM) in vitro. When T8+ or Leu3a+ cells from blood or synovial tissue from nine patients were substituted for T8+ or Leu3a+ cells, respectively, from normal blood mononuclear cells (MNC), RA T8+ cells showed an increased suppressor activity, whereas RA Leu3a+ cells were, except for one patient, weak augmentors. Unreplaced normal MNC and MNC replaced with allogeneic normal T-cell subpopulations responded equally to PWM. When T8+ plus Leu3a+ cells from the same patient replaced normal T cells, high B-cell responses were detected. Normal T8+ plus Leu3a+ cells generally supported the response to a lower degree. Substitution with two allogeneic T-cell subpopulations did not result in a B-cell response to PWM. Thus, whereas RA T8+ seemed to be strong suppressors and RA Leu3a+ cells weak augmentors by themselves, together they are possibly able to generate a B-cell stimulatory potential that might be of pathogenetic significance in the patients.
6602019 Prostaglandin-mediated immunoregulation: reduced sensitivity of in vitro immunoglobulin pr 1983 Mar Spontaneous and pokeweed mitogen (PWM) stimulated in vitro immunoglobulin production from peripheral blood mononuclear cells (PBMC) of control subjects and rheumatoid arthritis (RA) patients both receiving non-steroidal anti-inflammatory drugs (RA + NSAID) was measured by an enzyme linked immunosorbent assay (ELISA). Spontaneous IgG and IgM-RF production from the RA + NSAID was significantly higher than in control subjects. IgM production was also elevated but not significantly. Indomethacin (10(-6) - 10(-8)M) added to in vitro cultures failed to influence spontaneous production from either group. PWM stimulated IgG production was not significantly different between the two groups whilst IgM synthesis was significantly reduced in the RA individuals. IgM-RF production was observed only in the RA + NSAID group. Indomethacin inhibited PWM stimulated IgG and IgM production in control individuals but was significantly less potent on IgG, IgM and IgM-RF production from the RA + NSAID group. This reduction in the inhibitory effect of indomethacin correlated significantly with the high spontaneous immunoglobulin production and a low PWM stimulation index observed in the RA + NSAID group. Indomethacin had no significant effect on PWM stimulated PBMC proliferation in the rheumatoid individuals. These results suggest that B lymphocytes from some RA + NSAID are 'pre-committed' to produce immunoglobulins spontaneously in culture, possibly as a consequence of activation in vivo, and are therefore relatively insensitive to PWM stimulation. These B lymphocytes may have progressed beyond the immunoregulatory steps involving prostaglandins.
6378208 Azathioprine versus D-penicillamine in rheumatoid arthritis patients who have been treated 1984 Jul Two hundred six patients were entered into a prospective controlled, double-blind, multicenter trial comparing azathioprine (AZA) 1.25-1.5 mg/kg/day with D-penicillamine (DP) 10-12 mg/kg/day. One hundred thirty-four patients completed 24 weeks of therapy. Improvement in nearly all efficacy variables was seen in both groups. Patients taking DP demonstrated a greater rise in hemoglobin concentration and greater fall in erythrocyte sedimentation rate than patients receiving AZA; these were the only efficacy variables with a significant difference between the treatment groups. Fewer withdrawals for adverse reactions occurred among the patients receiving AZA, but the difference was not significant. Patients receiving AZA were withdrawn from the drug mainly for abnormal liver function test results, nausea and gastrointestinal upset, and leukopenia. The main reasons for withdrawal of patients receiving DP were nausea, rash and pruritus, thrombocytopenia, dysgeusia, and proteinuria.
60050 The role of the acute phase reaction in inflammation. 1976 Feb Inflammation and injury to tissue results in a variety of local and systemic events, however although the local events of oedema formation and cellular infiltration have received considerably more attention the systemic response to inflammation is no less profound. The particular systemic event which forms the substance of this communication is the change in the circulating levels of plasma proteins which occurs after inflammatory injury, and the manner in which these changes in plasma concentration are controlled by changes in plasma concentration are controlled by changes in the rate of synthesis. A discussion of the role of the liver in controlling inflammatory events, in relation to the synthesis of an anti-inflammatory protein has been given; the present work is an extension of this and describes the changes in concentration and synthesis rate of albumin, fibrinogen and alpha1 acid glycoprotein during adjuvant arthritis in the rat. The changes which occur are regulated at the liver by alteration of the rate of synthesis of the individual protein. For example albumin at the height of adjuvant arthritis falls to a third of its normal plasma level whereas the level of alpha1 acid glycoprotein increases up to twenty-fold; these changes are reflected by similar changes in their synthesis rate by the liver. The effect of the fall in albumin concentration on the plasma binding of anti-inflammatory drugs (and their toxicity) in relation to these findings will be discussed along with the biological role of the acute phase plasma proteins and hence the influence of the liver in the response to injury.
6432410 Changes in mononuclear cell function in patients with rheumatoid arthritis following treat 1984 Mar Gold salts in vitro modulate lymphocyte proliferation to mitogens and antigens and macrophage phagocytosis. These effects are not confined to gold salts; D-penicillamine and chloroquine as well as some of the non-steroidal anti-inflammatory drugs (NSAIDs) have in vivo immunoregulatory effects. Peripheral blood mononuclear cells during treatment with Myocrisin (gold sodium thiomalate, GSTM) show changes that differ from in vitro effects and are related to therapeutic response rather than GSTM administration. This discrepancy between in vitro and ex vivo responses prompted us to measure cellular functions during auranofin therapy. Twenty-nine patients with rheumatoid arthritis took part in a placebo-controlled trial of auranofin. We examined the spontaneous immunoglobulin (IgG and IgM) and IgM rheumatoid factor (IgM RF) production by cultured mononuclear cells, lymphocyte transformation to concanavalin A and macrophage phagocytosis of Candida albicans. There was a significant fall in IgG synthesis (p less than 0.005) and IgM RF synthesis (p less than 0.005) over the first 4 months of treatment, whereas in the control group there were no significant changes. There was no significant change in IgM production. In the auranofin-treated group the lymphocyte response to concanavalin A fell progressively during 6 months of therapy (at 2 months p less than 0.05, at 4 months p less than 0.01, and at 6 months p less than 0.005). Auranofin therapy had variable effects on monocyte phagocytosis of C. albicans. Therefore, in contrast to GSTM, auranofin suppressed both in vitro and ex vivo lymphocyte functions. This effect is probably related to the direct effect of auranofin on lymphocyte membranes.
314626 [Acute leukaemias after treatment using cytotoxic agents for rheumatological purpose. 19 c 1979 Apr 14 The authors undertook a retrospective study to determine the number of acute leukaemias developing amongst 2006 patients suffering from chronic inflammatory rheumatic conditions and connective tissue disorders, treated with cytotoxic agents. The follow-up period ranged from 1 to 13 years. Nineteen leukaemias were found, essentially granulocytic, with a latent period of 5.7 +/- 2, 8 years after the beginning of treatment. This incidence of almost 1% of leukaemias is probably less than the actual percentage since a number of patients were lost on follow up and since the period of observation is as yet too short. The majority of patients has been treated for more than one year. No cases were seen amongst patients treated for less than six months, or with less than 1g of chlorambucil or 50 g of cyclophosphamide. The risk would seem to be the same for both alkylating agents. No patients treated with azathioprine developed leukaemia, but few patients received this drug. Amongst 35 patients treated for severe psoriatic arthropathy with chlorambucil, 4 developed leukaemia. This particularly high percentage is such that all trials of alkylating agent in this condition should be stopped. The prevalence of leukaemia seen in the series as a whole is comparable to that found in mass studies carried out in various malignant diseases treated by cytotoxics. Awareness of this risk should, lead to even stricter limitations before the use of cytotoxic drugs in rheumatological conditions.
6445743 Effects of corticosteroids on the proliferation of normal and abnormal human connective ti 1980 Jan Four corticosteroids were tested in vitro for effect on the proliferation of four strains of fibroblasts from scleroderma skin, four strains from normal adult skin and four strains of rheumatoid synovial cells. Significant effects on fibroblasts occurred only at the highest steroid concentration tested (10 microgram/ml) where the inhibitory ranking of the steriods was clobetasol propionate greater than clobetasone butyrate greater than betamethasone valerate greater than hydrocortisone. Hydrocortisone and betamethasone valerate stimulated proliferation of two normal strains, had no certain effect on the scleroderma group, and inhibited growth of synovial cells. Clobetasone butyrate and clobetasol propionate inhibited growth of all cells. All four steroids substantially reduced acid mucopolysaccharide secretion by scleroderma fibroblasts. These results suggest that fibroblasts from normal and abnormal skin show only small differences in their responses to corticosteroids in vitro, but contrast sharply with the mouse L-929 fibroblasts previously used in some assays of topical corticosteroid potency.
6217534 Platelets as target cells in rheumatoid arthritis and systemic lupus erythematosus: a plat 1982 Sera from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were assessed for in vitro platelet activation as measured by serotonin release; 24% (30) of 124 tested RA sera and 51% (35) of 69 SLE sera induced a significant 3H serotonin release. Investigation of 17 synovial fluid samples from RA patients revealed significant release in 82%. Concomitant testing for lymphocytotoxic antibodies and immune complexes did not show any correlation to platelet activation. Upon gel filtration the release-inducing activity of positive sera was localized in the region of 160 000 Daltons. Further characterization by ion exchange chromatography, immune electrophoresis, chromatographic and SDS PAGE molecular weight determinations, as well as analytical ultracentrifugation all confirmed the IgG nature of the release-inducing protein. Negative blocking experiments performed by preincubation of platelets with Fc-IgG fragments prior to challenge with a release-inducing serum excluded the participation of Fc receptors in the reaction. It was concluded that the release was caused by a platelet reactive IgG antibody. This antibody may also cause release of platelet mediators in vivo and may thus contribute to the pathogenesis of the generalized vasculopathy in both diseases.
4627265 IgG, IgA and IgM responses in acute rubella determined by the immunofluorescent technique. 1972 Sep The indirect immunofluorescent technique has been used to study the specific immunoglobulin responses in twelve adult cases of acute uncomplicated rubella. IgG, IgA and IgM antibodies increased virtually simultaneously. IgG antibody persisted throughout the period of study but showed a slight tendency to fall in titre after 7 months. IgM antibody was detected in nine cases. In these patients it was present in high titre 5-15 days after the rash but was not detected after 20 days. IgA antibody was detected in all cases. It was present in high titre 5-20 days after the rash but was no longer detectable after 29 days except in one patient who had a very low titre at 78 days. The presence of specific IgA and IgM indicates recent rubella in uncomplicated cases, and if the immunofluorescent method is used both types of antibody should be sought.
6219450 Multiple abnormalities in immunoregulatory function of synovial compartment T cells in pat 1982 Analyses of the synovial tissue and fluid T lymphocytes obtained from patients with rheumatoid arthritis revealed multiple functional defects in the regulation of autologous blood B cell differentiation into cells secreting immunoglobulin. These abnormalities were not found in peripheral blood T lymphocytes from the same patients. Although the patients selected showed elevated levels of T cells expressing the T8 differentiation antigen as well as Ia antigens there was little demonstrable suppression of the blood B cell differentiation. Furthermore, the synovial T cells exhibited only minimal helper or inducer activity when tested in the same system. In contrast, patient's blood T lymphocytes gave levels of help and suppression that were not distinguishable from that of normal individuals. Co-culture experiments of blood and synovial T lymphocytes did not reveal any evidence for enhanced suppression; indeed, in most patients these co-cultures resulted in marked augmentation of helper function, a phenomenon designated "helper augmentation". These data provide evidence that rheumatoid synovial lymphocytes are characterized by marked abnormalities in immunoregulatory T cell function, including divergence of cellular activity from the immune function predicted by surface phenotype and a capacity for "helper augmentation", a novel T cell function in man.
6128763 Systemic vasculitis in a district general hospital 1972-1980: clinical and laboratory feat 1982 Summer Between 1972 and 1980 a histological diagnosis of vasculitis was made on 80 patients from a district general hospital. These were divided into a polyarteritis nodosa (PAN) group, a rheumatoid vasculitis (RV) group and a heterogeneous group of other vasculitides. There was considerable overlap between the clinical and laboratory features in the three groups. Non-specific symptoms (fever and myalgia), leucocytosis and eosinophilia were the most useful features for distinguishing PAN from the other two groups. Hepatitis B infection was rare (two patients) and hypocomplementaemia was a feature of RV but not of PAN. The overall mortality was similar in each group. However, in PAN deaths due to vasculitis were more common within six months of diagnosis. Features associated with a poor prognosis were renal impairment, cutaneous and intestinal vasculitis in PAN; and neuropathy, weight loss and histological evidence of vasculitis at rectal biopsy in RV. Cytoxic drugs combined with corticosteroids were associated with an improved prognosis compared with corticosteroids alone in the PAN group. Pulmonary involvement was associated with less severe renal disease but with a six month mortality similar to that in the whole PAN group. Systemic vasculitis is not uncommon in a district general hospital population. The overlapping clinical and laboratory features in different vasculitic diseases stress the problems in classification between PAN and other groups. Patients with systemic disease complicated by necrotizing arteritis have a severe, life threatening disease which may respond to aggressive cytotoxic therapy.