Browse

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

ID PMID Title PublicationDate abstract
7538544 Oligoclonal CD8+ T cells are preferentially expanded in the CD57+ subset. 1995 Jun 1 A number of recent reports have established that oligoclonality and/or clonal expansion is a common feature of the CD8+ T cell population. Oligoclonal expansion has also been observed in bone marrow transplant recipients and rheumatoid arthritis patients, disease states in which CD57+CD8+ T cells are occasionally elevated. In this study we have compared the TCR repertoire of the CD57+ and CD57- subsets of CD8+ T cells in normal persons by using three-color FACS analysis with a panel of 16 mAbs specific for TCR V segments. The CD57 surface marker was highly variable in frequency but generally present on a minority of CD8+CD3+ T cells (mean 16.3%, SD 12.7) in a group of 41 normal volunteers. Dramatic oligoclonal expansion was present in the CD57+CD8+ T cell population in 15 of 41 (37%) of our study population and thus is a characteristic feature of the normal immune system. No such prominent oligoclonal expansions were observed in the CD57-CD8+ subset, although preliminary experiments suggest that oligoclonality per se is occasionally present at a lower frequency in CD57- cells. The reasons for this persistent accumulation of oligoclonal CD8+CD57+ T cells and their function in immune homeostasis are unclear.
7963542 Epitope mapping of the branched chain alpha-ketoacid dehydrogenase dihydrolipoyl transacyl 1994 Nov 15 Sera from 29 of 48 patients with idiopathic dilated cardiomyopathy (IDCM) and six of six patients with dilated cardiomyopathy (DCM) secondary to suspected viral myocarditis were shown to react with the branched chain alpha-ketoacid dehydrogenase (BCKD) complex mitochondrial proteins. Whereas sera from only 1 of 26 patients with ischemic heart disease showed reactivity against the BCKD complex protein, 0 of 30 sera from normal human volunteers, 0 of 64 sera from patients with lupus, and 0 of 34 sera from patients with rheumatoid arthritis showed detectable reactivity, denoting an element of specificity for the reactivity of sera from IDCM patients. The major reactivity was localized to the dihydrolipoyl transacylase (E2) component of BCKD complex. By using recombinant techniques, the immunodominant BCKD-E2 epitope recognized by sera from IDCM patients was localized to amino acid (aa) sequences 116 to 134. Each of the IDCM sera that reacted with the native BCKD complex was shown to react with the immunodominant peptide, as defined by a peptide inhibition ELISA and by an ELISA using the reactive peptide conjugated to BSA. Sera from IDCM patients that reacted with the native BCKD complex and the reactive peptide also showed inhibition of BCKD enzyme activity. The possible mechanisms for the induction of the Abs and the implications of these findings for the pathogenesis of IDCM are discussed.
7528372 Regulation of bone metabolism by the kallikrein-kinin system, the coagulation cascade, and 1994 Oct Inflammation-induced localized bone resorption in diseases such as marginal and apical periodontitis, rheumatoid arthritis, and osteomyelitis is due to activation and recruitment of osteoclasts by locally produced cytokines and inflammatory mediators. Thus several interleukins (1, 3, 4, 6, and 11), tumor necrosis factors (alpha, beta), colony-stimulating factors (M and GM), leukemia inhibitory factor, gamma-interferon, and transforming growth factor-beta have effects on bone resorption and bone formation in vivo and in vitro. The kallikrein-kinin system and the coagulation cascade are also activated in inflammation. We have found that peptides produced in the kallikrein-kinin system (bradykinin, kallidin) and thrombin, the end product in the coagulation cascade, can stimulate bone resorption in vitro. The stimulatory effect of bradykinin is linked both to B1 and B2 bradykinin receptors. Both kinins and thrombin stimulate prostaglandin biosynthesis in bone parallel with the bone resorptive effect. The stimulatory effect of bradykinin on bone resorption is completely lost when the prostaglandin response is abolished, whereas thrombin can stimulate bone resorption both via prostaglandin-dependent and independent mechanisms. In addition, bradykinin and thrombin act in concert with interleukin-1 to synergistically stimulate bone resorption and prostaglandin biosynthesis. We also have found that one of the acute-phase reactants, haptoglobin, can stimulate bone resorption in vitro, indicating the possibility of generalized bone loss in chronic inflammatory diseases. Moreover, haptoglobin synergistically potentiates bradykinin-induced and thrombin-induced prostanoid biosynthesis in osteoblasts. These observations indicate that the rate of bone resorption in inflammation-induced bone loss may not be due to a single factor but to the concerted action of several local or systemic factors.
8306500 Anti-proteinase 3 antibodies, their characterization and disease associations. 1994 Feb Anti-proteinase 3 antibodies are a subgroup of anti-neutrophil cytoplasmic antibodies (ANCA), and we have established an ELISA for their detection using high performance liquid chromatography (HPLC)-purified protein. This assay is sensitive and specific: inhibition studies have shown that despite the homology between proteinase 3 and elastase there is no cross-reactivity between the corresponding antibodies for their targets. Anti-proteinase 3 antibodies were associated most often with cytoplasmic fluorescence (17/22, 77%), but occasionally with a perinuclear (3/22, 14%) or atypical pattern (1/2). These antibodies were found in 23 out of 76 sera (30%) that were positive in an ELISA based on a crude neutrophil cytoplasmic extract, and they were associated with both 29 and 55 kD bands on Western blots. Anti-proteinase 3 antibodies were found in most individuals with active Wegener's granulomatosis (10/13, 77%), but less often in individuals with microscopic polyarteritis (2/10, 20%) or segmental necrotizing glomerulonephritis (3/6, 50%). However, anti-proteinase 3 antibodies were not detected in any of 32 sera from individuals with rheumatoid arthritis or systemic lupus erythematosus (SLE). Occasionally anti-proteinase 3 antibodies were associated with anti-glomerular basement membrane antibodies (1/11, 9%) or with anti-myeloperoxidase antibodies (1/11, 9%). IgM anti-proteinase 3 antibodies were uncommon (2/22 sera, 9%), and no IgA antibodies were demonstrated in any of 22 sera from patients with active systemic vasculitis. Significantly more individuals presented with anti-proteinase 3 antibodies in April-May-June, suggesting that an infective agent prevalent in Autumn might have a causative role in the associated diseases. Anti-proteinase 3 antibodies are the most common target antigen associated with Wegener's granulomatosis and cytoplasmic fluorescence.
8128031 [A high-resolution computed tomographic study of the pulmonary interstitium in systemic au 1994 Jan This study was aimed at assessing the diagnostic capabilities of radiologic imaging in systemic autoimmune diseases. Forty-one patients (37 women and 4 men, mean age: 57.9 years, range: 37-73) were examined: 17 of them had rheumatoid arthritis, 8 Sjögren's syndrome, 11 progressive systemic sclerosis, 3 systemic lupus erythematosus, 1 mixed connective tissue disease and 1 undifferentiated connective tissue disease. The clinical features were compared with chest X-ray and HRCT findings. Functional lung examination (spirometry) was performed in 30 patients and in 22 of them chest X-ray findings could be compared with HRCT results since the examinations were performed on the same day. Seventeen patients complained of dyspnea (41.4%) and CO diffusion was reduced in 53% of the investigated patients. Chest films showed interstitial changes in 14 of 22 patients (63.6%), while HRCT findings were abnormal in 90.2% of the patients. Significant changes in HRCT patterns were detected only in 7 of the patients complaining of dyspnea (41.1%) and in 5 of the patients with reduced CO diffusion. In conclusion, HRCT proved to be much more sensitive than plain chest films. Dyspnea and functional respiratory tests correlated poorly with HRCT findings.
7858955 Growth inhibition of macrophage-like and other cell types by liposome-encapsulated, calciu 1994 Bisphosphonates effectively inhibit osteoclastic bone resorption in diseases characterized by excessive bone loss. Liposome-encapsulated clodronate (dichloromethylene bisphosphonate) also is known to inactivate phagocytic cells in vivo, and inhibit the growth of macrophage-like RAW 264 cells in vitro. The macrophage suppressive effect of liposomal clodronate is of interest in autoimmune diseases, like rheumatoid arthritis, in which phagocytic cells are involved in inflammatory processes. Earlier in vivo studies suggested that liposomal clodronate is a far more potent inactivator of macrophages than liposomal forms of two other bisphosphonate compounds, pamidronate (3-amino-1-hydroxypropylidene bisphosphonate), and etidronate (1-hydroxyethylidene-1,1-bisphosphonate). We examined the growth inhibitory properties of these three bisphosphonates with macrophage-like RAW 264 cells and with other types of cells in vitro. All three bisphosphonates encapsulated in liposomes effectively inhibited the growth of RAW 264 and CV1-P cells, while free drugs were 20-1000 times less potent growth inhibitors. Also, high extracellular calcium concentrations enhanced the potency of bisphosphonates for RAW 264 cells, indicating that, in addition to liposomes, the uptake of bisphosphonates by macrophages is mediated also by calcium. In all formulations, pamidronate was the most potent compound for the cells, with the exception of CV1-P cells, for which liposomal clodronate was the most potent. The effects of liposomal drugs were selective for highly endocytotic cells. The results suggest that liposome-encapsulated bisphosphonates could provide a specific tool to affect the function of macrophages and all three of these bisphosphonates are potentially effective as macrophage suppressors in autoimmune diseases.
8097682 Antibodies to human recombinant lipocortin-I in inflammatory bowel disease. 1993 Apr 1. Corticosteroid drugs are widely employed for the treatment of active inflammatory bowel disease. Not all patients receiving corticosteroid treatment, however, respond satisfactorily, their disease either remaining active in spite of continued treatment, or relapsing upon corticosteroid withdrawal. Raised levels of autoantibodies to lipocortin-I, a corticosteroid-inducible protein with anti-inflammatory activity in vitro, in patients receiving chronic oral corticosteroid therapy have been associated with poor clinical response in rheumatoid arthritis. 2. To determine whether a similar mechanism is responsible for the variable clinical response to corticosteroids in inflammatory bowel disease, we have measured circulating lipocortin-I antibody levels in sera from affected patients and related them to disease activity, treatment and subsequent outcome. 3. IgM, but not IgG, lipocortin-I antibody levels were elevated in patients with ulcerative colitis and Crohn's disease compared with healthy control subjects. In patients with Crohn's disease not taking corticosteroids, IgM lipocortin-I antibody levels were directly related to disease activity scored clinically. 4. IgM lipocortin-I antibody levels were higher in patients receiving sulphasalazine or no treatment and in patients receiving corticosteroids who responded to treatment within 2 months (steroid responders) than in those patients undergoing long-term corticosteroid therapy because of continued disease activity or repeated relapse on corticosteroid withdrawal (steroid non-responders). 5. The high levels of IgM lipocortin-I antibodies in patients with inflammatory bowel disease not taking corticosteroids provides further evidence of disturbed immunity in inflammatory bowel disease.(ABSTRACT TRUNCATED AT 250 WORDS)
1429800 A normal data base of posteroanterior roentgenographic measurements of the wrist. 1992 Oct In 120 adults, we measured the dominant wrist on posteroanterior roentgenograms in order to determine the normal dimensions and variations according to age and sex. Men and women were equally represented as were two age-groups (twenty-five to forty years and forty-one to sixty years). The roentgenograms were made, with standard exposure and development techniques, with the wrist and forearm in a neutral position and the x-ray tube aligned vertical to the radial styloid. The roentgenogram that was made with the wrist in the mid-coronal plane was digitized and was used to measure distances between specified landmarks. The mean ulnar variance was -0.9 millimeter (normal range, -4.2 to 2.3 millimeters). The average carpal height ratio was 53 per cent (normal range, 46 to 61 per cent). The mean radial inclination was 24 degrees (range, 19 to 29 degrees). The carpal-radial and carpal-ulnar ratios were smaller in women. The width of the distal radio-ulnar joint was reduced in the older subjects. There was a significant positive relationship (p < 0.0001) between the maximum force reached and the length of the third metacarpal. We believe that information concerning the normal roentgenographic measurements and relationship between the bones of the wrist can be used (1) to follow the progression of carpal instabilities, osteonecrosis, osteoarthrosis, or rheumatoid arthritis; (2) in clinical research; and (3) in the design of wrist implants.
1591884 Presence of autoantibodies to peptidyl-prolyl cis-trans isomerase (cyclosporin A-binding p 1992 Apr Several autoantibodies against cytoplasmic or nuclear components of cells have been reported in autoimmune diseases. We report here a previously unrecognized autoantibody to peptidyl-prolyl cis-trans isomerase (PPIase) in patients with systemic lupus erythematosus (SLE). PPIase, which catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides, has recently been found to be identical to cyclophilin, a specific binding protein of a potent immunosuppressant, cyclosporin A. IgG and IgM anti-PPIase antibodies were detected in 40 and 20% of unselected patients with SLE, respectively, by ELISA. The reactivity of these sera was confirmed by immunoblotting experiments. Sera from rheumatoid arthritis patients showed no reactivity and 1 of 8 sera from systemic sclerosis patients and 1 of 25 sera from normal controls showed only weak reactivity. Unexpectedly, the anti-PPIase antibody was unable to inhibit PPIase activity, indicating that the autoantibody recognizes an epitope of PPIase which is different from the active site of PPIase. The levels of the anti-PPIase antibody in SLE patients correlated with remissions and flares of the disease. The anti-PPIase antibody was higher in patients with active SLE than those with inactive disease. The prevalence of the active stage of the disease was significantly higher in IgG anti-PPIase antibody-positive SLE patients as compared to antibody-negative SLE patients. These data define the presence of a new autoantibody against PPIase and its association with the activity and certain clinical manifestations in SLE.
1299346 Inhibition of human T lymphocyte proliferation and cytokine production by 1,25-dihydroxyvi 1992 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3), the biologically active form of vitamin D3, has been shown to modulate lymphocyte functions in vitro. These effects are exerted through binding to specific receptors that are expressed in activated, but not in resting lymphocytes. 1,25-(OH)2 D3 inhibits lymphocyte proliferation, immunoglobulin production and the release of cytokines including interleukin-2 (IL-2) and interferon gamma (IFN gamma) by mitogen driven blood mononuclear cells (MNC). A distinction between CD45RA+ and CD45R0+ subsets of T cells has, however, proven extremely relevant in terms of immunoactivation and immunopathology. The present study was undertaken to evaluate effects of 1,25-(OH)2 D3 on proliferation and cytokine production by purified CD45RA+ and CD45R0+ T cells. 1,25-(OH)2 D3 caused a dose- and time-dependent reduction in phytohemagglutinin-(PHA) and poke-weed mitogen (PWM)-driven proliferation of purified CD45R0+ T cells. In contrast, proliferation of the CD45RA+ subset was unaffected by this treatment. Comparable levels of lymphotoxin (LT), IFN gamma and IL-2 were obtained in cultures of both subsets. 1,25-(OH)2 D3 reduced these levels, but the suppressive effect of the hormone was delayed in cultures of CD45RA+ T cells. The results suggest that the CD45R0+ subset is relatively more sensitive than CD45RA+ subset to the inhibitory effects of 1,25-(OH)2 D3. This finding may be of pharmacological interest, because the CD45R0+ subset plays a key role in immune activation and because these cells have been associated with the pathogenesis of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis.
8952893 [A family of receptors for secretory phospholipases A2]. 1996 Venom phospholipases A2 (vPLA2's) display a large spectrum of toxic effects including neurotoxicity, myotoxicity, hypotensive, anticoagulant and proinflammatory effects. We have shown that these different types of effects are apparently linked to the existence of a diversity of very high affinity receptors (Kd values as low as 1.5 pM) for these toxic enzymes. On the other hand, mammalian secretory PLA2's (msPLA2's) are now implicated in many biological functions besides digestion, such as airway and vascular smooth muscle contraction, cell proliferation, and in a variety of diseases associated with inflammation such as rheumatoid arthritis, endotoxic shock, respiratory distress syndrome as well as in cancer diseases.... Several different types of receptors (N and M) have been identified for vPLA2's and one of them (180 kDa, called M) has been cloned in rabbit and man. It is a membrane protein with a N-terminal cystein-rich domain, a fibronectin-like type II domain, eight repeats of a carbohydrate recognition domain, a unique transmembrane and an intracellular C-terminal. When expressed in transfected cells, the rabbit M-type receptor binds both the inflammatory-type and the pancreatic-type msPLA2's with fairly high affinities (Kd approximately -1-10 nM) suggesting that the sPLA2 receptors we have identifying vPLA2's are the normal targets of endogenous msPLA2's involved in a variety of diseases. Residues within or close to the Ca2+ binding loop of pancreatic-type PLA2 are crucially involved in the binding step although the presence of Ca2+ which is essential for the enzymatic activity is not required for binding to the receptor. The domain in charge of sPLA2 binding in the M-type receptor has been identified. The M-type receptor is an endocytic receptor that rapidly internalizes its sPLA2 ligand.
7607676 Molecular cloning and chromosomal mapping of a bone marrow stromal cell surface gene, BST2 1995 Apr 10 Bone marrow stromal cells regulate B-cell growth and development through their surface molecules and cytokines. In this study, we generated a mAb, RS38, that recognized a novel human membrane protein, BST-2, expressed on bone marrow stromal cell lines and synovial cell lines. We cloned a cDNA encoding BST-2 from a rheumatoid arthritis-derived synovial cell line. BST-2 is a 30- to 36-kDa type II transmembrane protein, consisting of 180 amino acids. The BST-2 gene (HGMW-approved symbol BST2) is located on chromosome 19p13.2. BST-2 is expressed not only on certain bone marrow stromal cell lines but also on various normal tissues, although its expression pattern is different from that of another bone marrow stromal cell surface molecule, BST-1. BST-2 surface expression on fibroblast cell lines facilitated the stromal cell-dependent growth of a murine bone marrow-derived pre-B-cell line, DW34. The results suggest that BST-2 may be involved in pre-B-cell growth.
7531945 Expression of vascular permeability factor/vascular endothelial growth factor by human gra 1995 Jan Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is a cytokine that is overexpressed in many tumors, in healing wounds, and in rheumatoid arthritis. VPF/VEGF is thought to induce angiogenesis and accompanying connective tissue stroma in two ways: 1), by increasing microvascular permeability, thereby modifying the extracellular matrix and 2), as an endothelial cell mitogen. VPF/VEGF has been reported in animal corpora lutea and we investigated the possibility that it might be present in human ovaries and have a role in corpus luteum formation. We here report that VPF/VEGF mRNA and protein are expressed by human ovarian granulosa and theca cells late in follicle development and, subsequent to ovulation, by granulosa and theca lutein cells. Therefore, VPF/VEGF is ideally positioned to provoke the increased permeability of thecal blood vessels that occurs shortly before ovulation. VPF/VEGF likely also contributes to the angiogenesis and connective tissue stroma generation that accompany corpus luteum/corpus albicans formation. Finally, VPF/VEGF was overexpressed in the hyperthecotic ovarian stroma of Stein-Leventhal syndrome in which it may also have a pathophysiological role.
8024596 Construction and serological characterization of a recombinant human single chain T cell r 1994 Jun 30 A single chain T cell receptor (scTcr) was constructed from the complete V alpha and V beta regions of Jurkat T-cell receptor alpha/beta chain genes using molecular cloning techniques. The recombinant scTcr reacted with a panel of rabbit antisera generated against synthetic 16-mer peptides duplicating the amino acid sequence of Jurkat V alpha and beta chains but not with antisera directed against peptides from the constant domain. Autoantibodies present in sera from systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients bound the scTcr in ELISA assays. The recombinant scTcr described here should prove to be a useful reagent with which to study T-cell receptor activity in serological and functional assays.
7518683 Immune response to different sequences of the EBNA I molecule in Epstein-Barr virus-relate 1994 Apr Epstein-Barr virus (EBV) infection is associated with production of autoantibodies. The N-terminal 35-58 sequence of EBNA I, one of the nuclear antigens encoded by EBV, is highly homologous to the C-terminal 95-119 region of the ribonucleoprotein SmD. Autoantibodies specific for SmD are present only in systemic lupus (SLE) sera and are therefore considered a serological marker of SLE. We measured antibodies to the EBNA I 35-58 sequence in EBV-related diseases and in autoimmune disorders. Antibodies to the EBNA I 35-58 peptide were present in 30% of normal sera, 12% Burkitt lymphoma, 22% infectious mononucleosis, 25% rheumatoid arthritis, 38% SLE and 33% Sjogren's syndrome. Antibodies to the SmD 95-119 peptide were detectable in 32% of SLE sera, 17% infectious mononucleosis and 12% Burkitt lymphoma. The specificity of anti-EBNA I 35-58 antibodies affinity-purified from nine sera was analysed by means of an inhibition assay. Only anti-EBNA I 35-58 antibodies affinity-purified from SLE sera have a similar affinity for the viral peptide and the SmD C-terminal one; they also bind the recombinant SmD in western blot. The results indicate that antibodies to EBNA I 35-58 are produced in normals, in EBV-related diseases and in autoimmune disorder, but only SLE sera contain anti-viral antibodies cross-reactive with an autoantigen.
8202663 Inhibition of mitogen-induced response of human peripheral blood mononuclear cells by buci 1994 The mechanism of action of bucillamine, [N-(2-mercapto-2-methylpropionyl)-L-cysteine] (BC), a novel antirheumatic drug that is used in patients with rheumatoid arthritis (RA), was compared with that of D-penicillamine (DP). BC inhibited phytohemagglutinin (PHA)-induced DNA synthesis of peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner, and this inhibition occurred both in the presence and absence of copper, whereas DP-induced inhibition required the presence of cupric ions. Significant inhibition of DNA synthesis was observed at a BC concentration of 10 micrograms/ml. The disulfide form of BC, but not DP disulfide, suppressed the proliferation of PBMCs. After preincubation of human peripheral blood T lymphocytes or Møs with BC or DP, these cells were combined and the overall PHA response was estimated. Inhibition of the PHA response was observed following pretreatment of either T lymphocytes or Møs with BC, whereas inhibition was attained only when T lymphocytes were pretreated with DP and copper. As sulfhydryl agents produce hydrogen peroxide in the presence of cupric ions, the effect of catalase on DP- and BC-induced inhibition of PBMC DNA synthesis was examined. Catalase partially reversed the BC-induced inhibition of DNA synthesis of PBMCs, and it restored the inhibition by DP and copper almost to the control level. These results suggest that BC suppresses the function of both T lymphocytes and Møs in the mitogen response of PBMCs, whereas the action of DP is targeted at T lymphocytes.
8487361 Arteriovenous reversal for limb salvage in unreconstructible upper extremity arterial occl 1993 May PURPOSE: Peripheral vascular disease of the upper extremity as a result of atherosclerotic disease or systemic vascular disorders presents a difficult management problem to the vascular surgeon. When extensive distal disease is present bypass procedures with standard arterial reconstruction techniques may not be possible. The use of retrograde perfusion to deliver oxygenated blood to the capillary bed by means of a normal venous system is not new. Flow reversal has been attempted in the myocardial, cerebral, and distal extremity circulations. Arteriovenous reversal (AVR) has been described for limb salvage in patients with upper extremity ischemia, with variable results. METHODS: We performed six AVR procedures on five patients with diffuse distal arterial disease and limb-threatening upper extremity ischemia. Two patients had insulin-dependent diabetes, one had systemic lupus erythematosus (two extremities), one had rheumatoid arthritis with vasculitis, and the remaining patient had CRST (calcinosis, Raynaud's disease, sclerodactyly, telangiectasia) syndrome. The two patients with diabetes had systemic manifestations of atherosclerotic vascular disease and lower extremity ischemia; the remaining three patients had no evidence of atherosclerosis. In all patients the AVR was performed at the most distal site of nondiseased artery. RESULTS: Limb salvage was obtained in all cases; one patient had a healed minor digital amputation, and another patient had a healed major amputation. Clinical improvement with resolution of pain was achieved in five of six cases. The remaining patient had a significant diabetic neuropathy that was believed to contribute to her persistent pain. CONCLUSIONS: In patients with severe upper extremity ischemia not amenable to standard revascularization techniques, AVR should be considered to provide limb salvage and maximize hand function.
8329201 Defective HLA class II expression in monocytes of type 1 diabetic patients. The Childhood 1993 May Activation of T-helper cells is modulated by the intensity of HLA class II expression on antigen-presenting cells. We evaluated whether any abnormalities could be found in the expression of HLA-DR and -DQ molecules on monocytes in type 1 diabetic subjects. DR and DQ molecules were induced by human recombinant interferon-gamma on cultured peripheral blood monocytes obtained from children with type 1 diabetes (N = 28), their siblings (N = 18) and unrelated healthy controls (N = 21). The response in DQ induction varied considerably between different individuals, but the average responsiveness was significantly lower in patients compared to siblings and unrelated controls. In addition to the diabetic subjects deficient DQ induction was also observed in three siblings. One of them had high levels of islet cell antibodies and presented with diabetes 6 months later, and another had active rheumatoid arthritis. The response in DR induction was also slightly lower in patients than in siblings, but did not differ from that in unrelated controls. The results suggest abnormalities in the regulation of HLA class II expression in type 1 diabetic subjects possibly reflecting the ongoing autoimmune process.
1360033 Antinuclear autoantibodies in women with silicone breast implants. 1992 Nov 28 Clinical syndromes resembling autoimmune diseases have been reported in women who have had breast augmentation procedures. To see whether there is a humoral immune response in these diseases that is similar to the immune response in their idiopathic counterparts, we assessed the immunological specificity of antinuclear antibodies (ANAs) and certain epidemiological features in 24 patients, all of whom (with 1 exception) had received silicone gel breast implants. ANA specificities were identified by indirect immunofluorescence, immunodiffusion, western blot analysis, and immunoprecipitation of radiolabelled intracellular proteins. Of 11 patients who had symptoms and signs that met criteria for defined autoimmune diseases, 7 had scleroderma or subsets of this disorder and the others had systemic lupus erythematosus, rheumatoid arthritis, or overlapping autoimmune diseases. High ANA titres were present in 10 of these 11 patients and the ANA specificities were similar to those found in the idiopathic forms of the corresponding autoimmune diseases. Trauma, with resultant rupture of implants, accelerated onset of symptoms. 13 other patients had autoimmune disorders of a less clearly defined nature and low titres of ANAs whose specificities could not be identified. ANAs are associated with the development of autoimmune complications in women with silicone breast implants. Further studies are needed to see whether this relation is one of cause and effect and whether ANAs might be early serological markers preceding development of autoimmune symptoms.
1392054 A sensitive and relevant model for evaluating anti-inflammatory activity-papaya latex-indu 1992 Aug A new model employing latex of papaya as an inflammagen has been developed for testing anti-inflammatory activity. The latex (exudate) was harvested from the unripe papaya fruit, which had been dried under vacuum. The latex was then suspended in 0.05 M sodium acetate buffer. This suspension when injected in rat hind paw produced concentration-dependent inflammation. Of the 0.25% of this suspension, 0.1 ml was found ideal for evaluating anti-inflammatory activity of test drugs. This concentration produced 70%-100% inflammation lasting for about 5 hr with a maximum effect at h 3. The test drugs employed were prednisolone, aspirin, indomethacin, phenylbutazone, ibuprofen, piroxicam, chloroquine, levamisole, and a mixture of boswellic acids. For comparison, these drugs were also tested against carrageenan-induced inflammation. All the test drugs--steroidal, aspirin, and non-aspirin-like--showed anti-inflammatory activity against latex-induced inflammation. The activity of chloroquine, levamisole, and boswellic acids was significantly more against latex as compared with that of the carrageenan model. The inflammation caused by latex may be attributed to both its hydrolytic enzymes--papain and chymopapain--and glutathione, the activator of these enzymes. These enzymes seem to act like lysosomal enzymes that are released in inflammatory disease processes which mediate inflammation by stimulating the synthesis of prostaglandins. The papaya latex-induced inflammation model appears to be a sensitive, broad-based, and relevant one likely to prove useful for discovering new and effective drugs against inflammation and rheumatoid arthritis.