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ID PMID Title PublicationDate abstract
1593589 Elbow synovitis related to an intraarticular osteoid osteoma of the humerus, with immunolo 1992 Apr An 18-year-old boy presented with elbow synovitis. Investigations disclosed an osteoid osteoma of the coronoid fossa confirmed by histology. The synovium appeared hypertrophic with histologic patterns resembling those seen in synovitis in rheumatoid arthritis. Immunohistochemistry showed lymphoid follicles composed of B and T cells. T lymphocytes were mainly of the CD4 phenotype, showing soluble interleukin 2 receptor (IL-2r) in places but were poorly positive for DR antigen. C3, C4, B factor and CH50 activity were decreased and interleukin 1 and soluble IL-2r were increased in synovial fluid. They were normal in peripheral blood except for a slight decrease in C4. These data suggest a local immunologic activation induced by osteoid osteoma, the mechanism of which remains hypothetic. Immunomodulating mediator diffusion from osteoid osteoma itself or as a secondary response to tumoral antigen release could be advocated. Whether such phenomena are specific to the epiphyseal location of osteoid osteoma needs clarification.
1503637 Inhibition of T cell activation by MHC blockade: a possible strategy for immunointerventio 1992 Apr Autoimmune diseases result from the activation of self-reactive T cells induced by autoantigens or by foreign antigens cross-reactive with an autoantigen. A striking characteristic of autoimmune diseases is the increased frequency of certain HLA alleles in affected individuals. Moreover, as demonstrated for example in rheumatoid arthritis and insulin-dependent diabetes mellitus, class II alleles positively associated with autoimmune diseases share amino acid residues in the hypervariable HLA regions involved in peptide binding. Therefore, it is likely that disease-associated HLA class II molecules have the capacity to bind the autoantigen and present it to T cells, thereby inducing and maintaining, under appropriate conditions, the autoimmune disease. The data reviewed here demonstrate MHC-selective inhibition of antigen-induced T cell responses in vivo by parenterally administered soluble, MHC-binding peptide competitors, under conditions in which the competitor is not immunogenic. This suggests the feasibility of a therapeutic approach based on blockade of MHC class II molecules in the treatment of HLA-linked autoimmune diseases.
8694578 Protection against peroxynitrite dependent tyrosine nitration and alpha 1-antiproteinase i 1996 Jun OBJECTIVE: To examine in vitro the ability of several drugs to protect against deleterious effects of peroxynitrite, a cytotoxic agent formed by reaction of nitric oxide with superoxide radical, that may be generated in the rheumatoid joint and could cause joint damage. METHODS: The ability of several drugs to protect against such possible toxic actions of peroxynitrite as inactivation of alpha 1-antiproteinase and nitration of tyrosine was evaluated. RESULTS: Most non-steroidal anti-inflammatory drugs were moderately (indomethacin, diclofenac, naproxen, tolmetin) or only weakly (sulindac, ibuprofen, aurothioglucose, flurbiprofen, sulphasalazine, salicylate, penicillamine disulphide) effective in preventing tyrosine nitration and alpha 1-antiproteinase inactivation by peroxynitrite, but 5-aminosalicylate and penicillamine were much more effective, as was the antibiotic tetracycline (but not ampicillin). Phenylbutazone and flufenamic acid protected effectively against tyrosine nitration, but could not be tested in the alpha 1-antiproteinase system. The analgesic paracetamol was highly protective in both assay systems. CONCLUSION: Many drugs used in the treatment of rheumatoid arthritis are unlikely to act by scavenging peroxynitrite. The feasibility of peroxynitrite scavenging as a mechanism of penicillamine, 5-aminosalicylate, and paracetamol action in vivo is discussed.
1311942 Decreased plasma superoxide scavenging activity in immunological disorders--carboxyethylge 1992 We investigated so-called superoxide scavenging activity (SSA) of plasma in patients with several immunological disorders, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), polymyo-dermatomyositis (PM), progressive systemic sclerosis (PSS), myasthenia gravis (MG) and autoimmune thyroid disease (AT), using the electron paramagnetic resonance/spin trapping technique. Since carboxyethylgermanium sesquioxide, Ge-132, has been reported to modulate both the immune response and leukocyte functions, we have studied in vivo effect of Ge-132 on plasma SSA and other laboratory parameters in these disorders. The plasma SSA was significantly lower in RA, SLE, PM and PSS, but not in MG and AT, as compared with that in healthy controls. An inverse correlation was observed between plasma SSA and parameters such as erythrocytes sedimentation rates, absolute number of leukocytes, C-reactive protein and serum globulin levels. Furthermore, plasma SSA was significantly decreased in rheumatoid factor-positive patients as compared to negative patients. No correlation was observed between plasma SSA and factors such as ages, sex of patients or the other laboratory parameters, such as serum albumin, triglyceride, cholesterol, hemoglobin and serum iron levels. Patients treated with prednisolone, especially ones with RA, showed an increase of plasma SSA. It appears that Ge-132 promotes prednisolone effects. Our results indicate that a decrease in plasma SSA is not disease specific, but inversely correlates with the severity and activity of inflammation. The methodology to measure plasma SSA presented in this work provides a helpful tool for determining the actual activity of the diseases as well as in vivo studies of antiinflammatory agents.
24193030 Oxygen radical induced fluorescence in proteins; identification of the fluorescent tryptop 1992 Jun The effect of oxygen derived free radicals (OFR) on aromatic and sulphur containing amino acids has been investigated, both in their free form and within protein backbones. Aerated amino acids and proteins in solution were exposed to three discrete OFR generating systems; (1) gamma radiation in the presence or absence of formate (2) photolysis by UV light at 254 and 366 nm, and (3) site specific modification by H2O2 in the presence of CuII ions.A sensitive reverse-phase HPLC technique with dual detection systems (UV absorbance and fluorescence monitoring) was developed to analyse the products of amino acid oxidation. OFR denatured amino acids were chromatographed by this procedure, and all radical species generated, with the exception of the superoxide anion, resulted in the formation of identifiable fluorescent metabolites of tryptophan, kynurenines. The identity of peaks was confimed by spiking with authentic material and scanning absorption spectroscopy. After complete proteolytic hydrolysis, OFR treated proteins were also analysed by this technique; again the dose dependent production of kynurenines was detected in IgG,γ lens crystallins and albumin. Bityrosine was not detected in any of the proteins studied using this procedure, however, several novel unidentified fluorophores were detected in proteolytic hydrolysates, possibly the product of two different amino acid radicals.Immunoglobulin G isolated from the sera of normals and rheumatoid arthritis (RA) patients was examined for the presence of one specific tryptophan metabolite, N-formyl kynurenine. Significantly elevated levels of this metabolite were detected in rheumatoid sera, suggesting increased OFR activity in RA.These results have demonstrated firstly, that specific oxidised products of amino acids are retained in the protein backbone after exposure to OFR generating systems. Secondly, in aerated solution, oxidised tryptophan residues confer the major new visible fluorescence in non-haem proteins, not tyrosine products. In addition, this work has demonstrated that the measurement of a specific product of an oxidised amino acid can be applied to biological macromolecules, and may be important in implicating free radical reactions in certain disease processes.
8913793 In vitro and in vivo biological activities of a novel nonpolyglutamable anti-folate, MX-68 1996 Oct MX-68 is a newly synthesized anti-folate, chemically designed not to undergo intracellular polyglutamation and to have increased affinity to dihydrofolate reductase (DHFR). In the present study, we examined the in vitro and in vivo biological activities of MX-68 compared with methotrexate (MTX) which forms several polyglutamates intracellularly. MX-68 dose-dependently inhibited the proliferation of PHA-, anti-CD3-, or PMA plus ionomycin-stimulated peripheral blood mononuclear cells (PBMC) and endothelial cells (EC) from normal subjects as well as IL-1 beta- or TNF alpha-stimulated synovial fibroblastic cells (SC) from rheumatoid arthritis (RA) patients. Coaddition of folinic acid completely reversed the anti-proliferative effects of both MX-68 and MTX. Although the anti-proliferative activities of MX-68 were almost comparable to those of MTX, the washout study clearly showed the characteristic nature of MX-68. When drugs were removed during culture, the suppressive effect of MX-68 completely disappeared, whereas suppression by MTX was merely weakened. MX-68 dramatically suppressed the onset of collagen-induced arthritis (CIA) in mice when the drug was orally administered three times a week. starting from the day of first immunization. In this model, 2 mg/kg of MX-68 was sufficient to completely suppress arthritis, whereas suppression by the same dose of MTX was partial. These lines of evidence suggest that polyglutamation is not always a prerequisite in the anti-rheumatic effects of anti-folate. In addition, since intracellular accumulation of polyglutamates is thought to have adverse effects, MX-68 may become a more potent and less toxic anti-rheumatic drug than MTX.
9115578 Different La/SS-B mRNA isoforms are expressed in salivary gland tissue of patients with pr 1996 Dec Recently we isolated a La/SS-B mRNA isoform from a cDNA library made from peripheral blood lymphocytes of a patient with primary Sjögren's Syndrome. In the La/SS-B mRNA isoform the exon 1 was replaced. The alternative exon was termed exon 1'. Genomic analysis showed that the exon 1' La mRNA was the result of a promoter-switch in combination with alternative splicing. Due to the unusual structure of the exon 1' La/SS-B mRNA, the function and the behaviour under physiological and pathophysiological conditions in tissue of patients with primary Sjögren's syndrome or Systemic Lupus Erythematosus remained obscure. Therefore assays were established allowing a qualitative and quantitative estimation of expression of the exon 1 and 1' La mRNA form, including in situ and dot blot hybridization as well as reversed PCR. Both mRNA forms were found to represent finally processed cytoplasmic mRNAs belonging to the abundant class of mRNAs. They were expressed and regulated in parallel. A ratio exon 1 to 1' between 1:1 and 5:1 was determined. Both mRNA forms were downregulated in quiescent cells and upregulated in activated and proliferating cells including non-keratized stratified squamous epithelial, endothelial, salivary gland as well as infiltrating cells.
8869626 T-cell-rich histiocyte-rich B-cell lymphoma of parotid gland. 1996 Aug We describe a malignant lymphoma of the parotid gland arising in a patient with Sjögren's syndrome. Diagnosis was established on needle biopsy which showed a mixed population of lymphoid cells. Immunohistochemistry revealed B-lymphoid cells, T-lymphoid cells and histiocytes. Clonal immunoglobulin heavy chain gene rearrangement was demonstrated using the polymerase chain reaction. Within the confines of the small biopsy, the lesion qualifies for the designation T-cell-rich histiocyte-rich B-cell lymphoma. The value of molecular techniques in the diagnosis of malignant lymphoma on limited tissue samples is highlighted by this case.
8933283 Estimation of the frequency of self-reactive T cells in health and inflammatory diseases b 1996 Oct Autoreactive T cells have recently been detected not only in autoimmune diseases but also in healthy individuals, but their frequency is thought to be low. The aim of our study was to estimate the frequency of self-reactive T cells by using limiting dilution analyses of peripheral blood lymphocytes. Assessment of self-reactivity in this study was defined as T-cell proliferation to autologous non-T cells in the absence of foreign antigens. When culture conditions were optimized by adding interleukin 2, healthy individuals showed a frequency of self-reactive T cells ranging from 1/60 to 1/600. These results were confirmed by using unseparated peripheral blood leukocytes or Epstein-Barr virus transformed B-cell blasts as stimulators. All cultures were performed exclusively in autologous serum. Single cell cloning from a healthy donor yielded 568 T-cell clones, 12 of which showed self-reactivity giving a frequency of more than 1 in 50 T cells. Eight of these 12 T-cell clones were inhibited by MHC-class II antibodies. Frequency analyses of self-reactive T cells in patients with autoimmune diseases (rheumatoid arthritis, autoimmune hepatitis or primary biliary cirrhosis), with viral hepatitis or with inflammatory bowel diseases showed similar frequencies in all patient groups and no significant differences from normal individuals. In conclusion, we have found a high frequency of self-reactive T cells in both health and disease. We postulate that self-reactive T cells constitute an important part of the physiological T-cell repertoire.
8790602 X chromosome inactivation patterns correlate with fetal-placental anatomy in monozygotic t 1994 Nov BACKGROUND: Monozygotic (MZ) twinning is a poorly understood phenomenon that may result in subtle biologic differences between twins, despite their identical inheritance. These differences may in part account for discordant expression of disease in MZ twin pairs. Due to their stochastic nature, differences in X chromosome inactivation patterns are one source of such variation in female MZ twins. MATERIALS AND METHODS: We investigated X chromosome inactivation patterns in the blood of 41 MZ twin pairs based on methylation of the androgen receptor gene using a Hpa II-PCR assay. Twenty-six female MZ twin pairs with autoimmune disease (rheumatoid arthritis or multiple sclerosis) were studied. In addition, we studied 15 newborn female MZ twin pairs who were characterized at birth with respect to the anatomy of chorionic membranes (dichorionic versus monochorionic). RESULTS: We found a strong correlation between dichorionic fetal anatomy and differences in X chromosome inactivation patterns between members of an MZ twin pair. In contrast, all monochorionic twin pairs had closely correlated patterns of X chromosome inactivation. X chromosome inactivation patterns did not distinguish between MZ twin pairs who were concordant or discordant for autoimmune disease. CONCLUSIONS: The highly similar patterns of X chromosome inactivation among monochorionic twin pairs may result from their shared placental blood supply during intrauterine life. Alternatively, these patterns may indicate that X chromosome inactivation occurs before the twinning event in this anatomic subgroup of MZ twins. The data further suggest that these factors do not make a major contribution to the high discordance rates for autoimmune disease in MZ twin pairs.
9023058 Chemokine-leukocyte interactions. The voodoo that they do so well. 1996 Dec Leukocyte recruitment from the circulation into inflammatory tissues requires a series of soluble and cell-bound signals between the responding leukocyte and vascular endothelial barrier. Chemotactic factors are believed to be responsible for this selective adhesion and transmigration. A superfamily of small, soluble, structurally-related molecules called 'chemokines' have been identified and shown to selectively promote the rapid adhesion and chemotaxis of a variety of leukocyte subtypes both in vivo and in vitro. Chemokines are produced by almost every cell type in the body in response to a number of inflammatory signals, in particular those which activate leukocyte-endothelial cell interactions. These molecules also appear to play important roles in hematopoesis, cellular activation, and leukocyte effector functions. In addition, chemokines have been found in the tissues of a variety of disease states characterized by distinct leukocytic infiltrates, including rheumatoid arthritis, sepsis, atherosclerosis, asthma, psoriasis, ischemia/reperfusion injury, HIV replication, and a variety of pulmonary disease states. This review will primarily focus on the role of chemokines in cell adhesion and trafficking as well as their role as effector molecules.
8842488 Regulation of VEGF/VPF expression in tumor cells: consequences for tumor growth and metast 1996 Jun Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF) is a multifunctional cytokine which potently stimulates angiogenesis in vivo. VEGF/VPF expression is elevated in pathological conditions including cancer, proliferative retinopathy, psoriasis and rheumatoid arthritis. The angiogenesis associated with human tumors is likely a central component in promoting tumor growth and metastatic potential. The regulation of VEGF/VPF expression during tumor progression may involve diverse mechanisms including activated oncogenes, mutant or deleted tumor suppressor genes, cytokine activation, hormonal modulators, and a particularly effective activator, hypoxia. Understanding the diverse mechanisms by which tumor cells overexpress VEGF/VPF, and which mechanisms are operating in specific tumor types is important for the design of effective anti-cancer therapies.
8850077 [Treatment concepts of femoral fractures after total endoprosthetic replacement of the hip 1996 Jan A comparison between intramedullary (n = 13) and extramedullary (n = 37) stabilization was performed in 50 patients (mean age 67.4 years) after fractures of the femoral shaft following knee or hip arthroplasty. Fracture of the femoral shaft (mean 5.5 years after the implantation) is observed especially often in patients with osteoporosis, loosening of the prosthesis, and rheumatoid arthritis. The ratio between cemented and uncemented endoprosthesis was 4:1. The investigation shows that extramedullary stabilization by means of plates and screws is the preferred treatment for younger patients and in the case of distal fractures, while in older people intramedullary fixation in combination with an additional osteosynthesis allows early mobilization. The number of complications observed is higher than with primary arthroplasty. The frequency of further operations, postoperative fractures and unsatisfactory results is significantly higher than in primary hip and knee surgery or uncomplicated fracture of the femur.
8805017 The glucocorticoid insensitivity syndrome. 1996 Recent studies demonstrate that primary (hereditary) abnormalities in the glucocorticoid receptor gene make 6.6% of the normal population relatively 'hypersensitive' to glucocorticoids, while 2.3% are relatively 'resistant'. These abnormalities might explain the well-known phenomenon that some individuals develop severe adverse effects during therapy with a low dose of glucocorticosteroids, while others do not develop side effects even during long-term therapy with a much higher dose. This heterogeneity in glucocorticoid sensitivity in the normal population might eventually allow the prediction of a 'safe' dose of glucocorticosteroids in individual patients. 'Resistance' to the beneficial clinical effects of glucocorticosteroid therapy in some patients with severe rheumatoid arthritis and asthma is probably seldom related to generalized primary (hereditary) glucocorticoid resistance. In most patients this 'resistance' seems to be acquired and localized to the inflammation sites, where it is caused by high local cytokine production which interferes with glucocorticoid action. Recognition of localized, acquired glucocorticoid resistance is of great importance, as alternative drug therapy with other immune-modulating drugs, such as cyclosporin and methotrexate, should be considered. Chronic high-dose glucocorticosteroid treatment in such patients insufficiently reduces symptomatology, while generalized side effects occur, as the rest of the body of the patient has a normal sensitivity to these drugs.
8551672 [Postgravid health care and laboratory tests]. 1995 Nov Various diseases often occur after delivery but the systemic examinations have not been studied before. Thyroid dysfunction frequently (4.4%) occurs after delivery through an immune rebound mechanism. If postpartum women complain of the symptoms caused by thyrotoxicosis (palpitation, weight loss, increased sweating, finger tremor, fatigue) or hypothyroidism (edema, cold intolerance, hoarseness, sleepiness, fatigue), it is essential to examine thyroid hormones, thyroid stimulating hormone, anti-thyroid microsomal antibody (MCHA) and anti-TSH receptor antibody. To predict who will develop postpartum thyroid dysfunction, the measurement of MCHA during pregnancy is useful because 62% of the subjects with positive MCHA show thyroid dysfunction after delivery. The individuals at high risk of postpartum onset of Graves' thyrotoxicosis can be found early in their pregnancy by the detection of thyroid stimulating antibody (TSAb). Other autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, autoimmune hypophysitis and so on, also could develop after delivery. These findings indicate that laboratory tests in the postpartum period are essential to diagnose postpartum onset of autoimmune diseases and the measurement of autoantibodies in early pregnancy is useful for prediction of their onset in the postpartum period.
7493765 T cell receptor usage in autoimmune disease. 1995 Aug Activated T-cells are believed to play a critical role in the pathogenesis of autoimmune disease. In experimental allergic encephalomyelitis (EAE), an animal model resembling human multiple sclerosis (MS), there is evidence that T cells reactive to myelin basic protein mediate an inflammatory response within the central nervous system leading to demyelination. Furthermore, encephalitogenic T cells express TCR with highly restricted V gene usage and consequently specific forms of immunotherapy directed against V gene products have been successful in preventing and treating EAE. These findings prompted studies into the analysis of TCR repertoire expression in human autoimmune diseases in an attempt to identify the TCR usage of autoreactive and potentially pathogenic T cells. However, this has proved difficult as the autoantigens that drive the T cell response in most human autoimmune disorders are unknown. This review examines the data that have accumulated over the past few years on TCR usage in human autoimmune diseases and is focused largely on rheumatoid arthritis and MS.
7543074 [Bioassay for angiogenesis and analysis of its mechanism]. 1995 May To study the sites of action of cytokines and anti-angiogenic agents, bioassays have been developed to systematically investigate not only the entire process of angiogenesis in vivo but also its individual steps including capillary tube formation and proliferation of vascular endothelial cells (EC). Angiogenesis in vivo is quantitatively assayed by measuring the carmine dye content in Freund's complete adjuvant-induced mouse pouch granuloma after the intravenous administration of dye solution. Angiogenesis in vitro is quantified by counting the number of microvessels developed from blood vessels cultured in fibrin gel. Tube formation is quantitatively estimated by measuring the total length of capillary tubes from EC cultured in type I collagen gel. EC proliferation is assayed by measuring both the increase in cell number and 3H-thymidine incorporation into the cells. The competence and progression activities in the EC proliferation are analyzed by our convenient method. By these bioassays, the mechanism of an anti-differentiation agent can be easily clarified to develop new types of therapies for rheumatoid arthritis and diabetic retinopathy.
7739124 [Measurement of anti-acetylcholine receptor antibody using human rhabdomyosarcoma cell lin 1995 Apr We developed a radioimmunoassay for AChR Ab using AChR solubilized from membrane extracts of human rhabdomyosarcoma cell line (RD cell). The binding affinity of this AChR to the alpha-Bungarotoxin (alpha-BTX) was similar to that of AChR from cell surface. Lyophilized AChR was stable within two months at -20 degrees C. In our assay system, sera from patients with Myasthenia Gravis (MG) showed markedly high titers and frequency (94%) of anti-AChR Ab. On the other hand, almost all sera from normal and non-myasthenic patients such as rheumatoid arthritis and thyroid disease were negative (< 0.2nmol/l). Our assay using AChR from RD cells shows sufficient results in the intra- and inter-CV values, and recovery and dilution tests. AChR Ab titers of our assay showed good correlations with those measured by AChRs from both human ischemic muscles and TE671 cells (commercial kit). The radioimmunoassay for AChR Ab using the membrane extracts of RD cells has high sensitivity, specificity and stability. Therefore, the assay is valuable as the routine assay for the diagnosis of MG.
7656468 Estrogens, the immune response and autoimmunity. 1995 Mar Estrogens appear to play a central role in the immune response and immune-mediated diseases. Recent studies have shown the presence of estrogen receptors on the cells involved in the immune response, namely thymocytes, macrophages and endothelial cells. Particular attention has been focused on the dose-dependent influence of estrogen on the immune response, which appears to be related to the clinical symptoms of autoimmunity (i.e. the effects of pregnancy or oral contraceptive pills). The influence of estrogens on cytokine production by target cells, through interference with their transcriptional activity, has also been the focus of various studies. The effect of estrogens on the expression of the protooncogenes and oncosuppressor genes involved in programmed cell death (apoptosis) might also be relevant to human autoimmunity, in particular the uncontrolled synovial lining cell hyperplasia associated with rheumatoid arthritis and the prolonged T-cell survival in systemic lupus erythematosus. Estrogen-induced immunomodulation is a subject of growing interest and stimulating research.
7888354 Antineutrophil cytoplasmic antibodies and their relevance to the dermatologist. 1995 Feb The term vasculitis embraces a heterogeneous group of conditions which may occur as primary phenomena or secondary to disorders such as rheumatoid arthritis or systemic lupus erythematosus. Classification of vasculitis is often difficult in the absence of identifiable aetiological factors or specific serological markers. However, the primary systemic vasculitides can be segregated morphologically, according to the size of blood vessels involved and the presence of granulomata (Table 1). Recently, the discovery of circulating antineutrophil cytoplasmic antibodies (ANCA) in many patients with these disorders, whose differing specificities substantiate the histological classification, has led to interest being focused on their relevance in the development of vasculitis. This paper reviews the historical aspects of the detection of ANCA, and the value of these antibodies in the diagnosis and management of the primary systemic vasculitides likely to be encountered by the dermatologist. The clinical features in patients with these vasculitides are also outlined.