Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 55-year-old woman with a several-decade history of thyroid goiter is presented here as a case of myasthenia gravis complicated with hyperthyroidism and thymoma with serological evidence of systemic lupus erythematous (SLE). She had had right eyelid ptosis since July 1992, with a positive tensilon test. The acetylcholine receptor antibody titer was 4.01 nmol/L. A thyroid function test revealed T3: 162 ngidl, T4: 14.98 micrograms/dl, TSH:0.09 microIU/ml and positive anti-microsomal antibody (1:400). An MRI of the chest showed a thymoma in the left thymus. Other autoantibody screenings include ANA (1:320, speckled pattern) and anti-ds DNA (+) suggesting a serological association with SLE. After three courses of plasmapheresis, she received an extended maximal thymomectomy and a subtotal thyroidectomy. She was then treated with prednisolone, Mestinon, Eltroxin and discharged without complications. The coexistence of myasthenia gravis, hyperthyroidism, thymoma and a serological evidence of SLE have not previously been documented in the literature.
 ...
PMID:Myasthenia gravis complicated with hyperthyroidism, thymoma and serological evidence of systemic lupus erythematosus: a case report. 887 Mar 31

Cyclin B1 is the major component of M-phase promoting factor that plays a major role in the G2/M transition of cell cycle. We examined the expression of cyclin B1 at the protein and mRNA levels in the thymus of 12-week-old autoimmune and normal mice. We found an abundance of cyclin B1 protein (58 kDa) in the thymus of lupus-prone MRL-lpr/lpr mice, whereas the level of this protein was negligible in other strains. The level of the predominant cyclin B1 mRNA (1.7 kb) species was not markedly different in these strains, suggesting post transcriptional modification of cyclin B1 in the thymus of MRL-lpr/lpr mice. Southern blot analysis of cyclin B1 gene showed multiple forms of cyclin B1-related sequences in various murine genomes. Flow cytometry showed a significantly higher level of cells in the G2/M phase and a significantly lower level in the S phase in thymocytes of MRL-lpr/lpr compared to that in normal BALB/c mice, indicating an alteration of cell cycle machinery in thymocytes of MRL-lpr/lpr mice. Taken together, these data show that an upregulation of cyclin B1 protein and accumulation of thymocytes at the G2/M phase in MRL-lpr/lpr mice might play an important role in the aberrant development of T cells in these mice.
 ...
PMID:Cyclins and autoimmunity: cyclin B1 gene expression and restriction fragment length polymorphism in lupus-prone mice. 888 18

A side effect of therapy with procainamide and numerous other medications is a lupus-like syndrome characterized by autoantibodies directed against denatured DNA and the (H2A-H2B)-DNA subunit of chromatin. We tested the possibility that an effect of lupus-inducing drugs on central T cell tolerance underlies these phenomena. Two intrathymic injections of procainamide-hydroxylamine (PAHA), a reactive metabolite of procainamide, resulted in prompt production of IgM antidenatured DNA antibodies in C57BL/6xDBA/2 F1 mice. Subsequently, IgG antichromatin antibodies began to appear in the serum 3 wk after the second injection and were sustained for several months. Specificity, inhibition and blocking studies demonstrated that the PAHA-induced antibodies showed remarkable specificity to the (H2A-H2B)-DNA complex. No evidence for polyclonal B cell activation could be detected based on enumeration of Ig-secreting B cells and serum Ig levels, suggesting that a clonally restricted autoimmune response was induced by intrathymic PAHA. The IgG isotype of the antichromatin antibodies indicated involvement of T cell help, and proliferative responses of splenocytes to oligonucleosomes increased up to 100-fold. As little as 5 microM PAHA led to a 10-fold T cell proliferative response to chromatin in short term organ culture of neonatal thymi. We suggest that PAHA interferes with self-tolerance mechanisms accompanying T cell maturation in the thymus, resulting in the emergence of chromatin-reactive T cells followed by humoral autoimmunity.
 ...
PMID:Autoimmunity caused by disruption of central T cell tolerance. A murine model of drug-induced lupus. 910 33

Following administration of certain chemicals (heavy metals or lupus-inducing drugs), H-2s mice produce autoantibodies reacting with various nuclear antigens such as fibrillarin in the nucleolus and histones in chromatin. In the present study, we have immunized A.SW (H-2s) mice and their congenic counterparts A.BY (H-2b) mice with bovine thymus nuclei in Freund's adjuvant. As was previously observed with lupus-prone mice, such active immunization did not elicit antinuclear antibodies in any of the experimental groups. Surprisingly, the A.SW immunized with nuclei in adjuvant developed high titers of IgG antibodies that reacted exclusively with synthetic polycations. We obtained several monoclonal IgG antibodies from these mice and verified that these polycation-reactive antibodies were not directed against a specific nuclear antigen. The genetic analysis of the monoclonal antibodies further confirmed their clonal diversity. The mechanisms leading to the appearance of antibodies reactive with highly basic molecules in A.SW mice may be related to their predisposition to produce autoantibodies to cationic nuclear antigens (fibrillarin, histones) during chemically-induced autoimmunity.
 ...
PMID:Induction of anti-polycation antibodies in H-2s mice by immunization with nuclear antigens. 918 75

Recent reports suggest that DNA methylation is involved in the cause of autoimmune disease. We investigated the alteration of DNA methylation levels in lupus strains of mice, MRL/lpr as a model, which develop an age-dependent lymphadenopathy and autoimmune disease. DNA methylation levels of thymus and axillary lymph nodes in 20-week-old MRL/lpr mice, which are in an autoimmune disease state, were lower than those of 4-week-old MRL/lpr mice with no symptoms as yet. No significant changes were observed in MRL/+ strain mice, which seemed normal at least 20 weeks, while DNA methylation levels in the spleen of both strains of mice increased significantly from the age of 4 to 20 weeks. However, no significant changes of DNA methylation levels in peripheral blood were observed with ageing in MRL strains. Moreover, we clarified that administration of 5-azacytidine had a strong effect on longer survival of MRL/lpr mice and reduced DNA methylation levels in the axillary lymph nodes and spleen. The possible relevance of DNA methylation levels to the progression of autoimmune disease is discussed.
 ...
PMID:Alteration of DNA methylation levels in MRL lupus mice. 936 11

We report a 40-year-old Japanese woman with antiphospholipid antibody syndrome (APS) associated with myasthenia gravis (MG). She had a history of miscarriage at the age of 27 followed by pulmonary embolism 3 weeks later. At the age of 40, she developed diplopia, bilateral ptosis and easy fatigability. Serum anti-acetylcholine receptor antibody and tensilon test were positive. She was diagnosed as having MG. The laboratory test revealed mild thrombocytopenia, prolonged activated partial thromboplastin time (aPTT) and positive findings for both beta 2-glycoprotein I-dependent anticardiolipin antibody and lupus anticoagulant. She fulfilled the diagnostic criteria of APS, but did not the criteria proposed by American Rheumatism Association for SLE. An extended total thymectomy was performed after administration of oral prednisolone and low-dose aspirin. This is a patient who had APS associated with MGs: both are known to result from autoimmune abnormality. The clinical and laboratory manifestations of APS were ameliorated after removal of the thymus, suggesting that thymectomy alleviates APS symptoms.
 ...
PMID:[A case of antiphospholipid syndrome associated with myasthenia gravis]. 939 64

Gonadotropin-releasing hormone (GnRH) is known to possess direct immunomodulatory effects. We have previously demonstrated that the administration of GnRH analogues modulates the expression of murine lupus independently of effects on gonadal steroids. We speculate that GnRH exerts direct actions at the level of the immune cells. GnRH receptors have been identified on lymphocytes. Because GnRH and GnRH receptor (GnRH-R) expression varies with the estrous cycle at the levels of the hypothalamus and pituitary, we speculated that similar cyclicity might be demonstrable in lymphoid tissue. In this report, we used competitive reverse transcription PCR to quantitate the expression of GnRH and GnRH-R mRNA in lymphoid organs throughout the estrous cycle in mice. We demonstrate that the pattern of expression of GnRH-R mRNA in spleen agrees closely with the pattern in the pituitaries of the same mice and the pattern previously reported in the rat pituitary, with significantly increased levels of expression seen on the afternoon of proestrus compared to the morning of metestrus. A similar pattern is seen with GnRH-R mRNA expression in the thymus. Furthermore, we show that the expression of GnRH mRNA in both thymus and spleen agrees closely with the pattern of expression of its receptor, with significantly increased levels of expression seen on the afternoon of proestrus compared to the morning of metestrus. Additional in vitro studies demonstrate that both GnRH and estradiol significantly increase the expression of GnRH-R mRNA in immune cells. These findings support an active role for GnRH in the immune system.
 ...
PMID:Cyclical expression of GnRH and GnRH receptor mRNA in lymphoid organs. 950 42

According to our concept, the development of autoimmune disease depends on the presence of two sets of essential genes, one coding for an abnormal autoreactivity of the immune system, the other for a primary susceptibility of the target organ/structure for the immune attack. The final outcome of the disease in a given individual is then fine tuned by modulatory factors, such as diet or hormones. With regard to the latter, the immuno-endocrine interaction via the hypothalamo-pituitary-adrenal (HPA) axis has proven to be of special importance. Investigating the so-called Obese strain (OS) of chickens, an animal model with a spontaneously occurring Hashimoto-like autoimmune thyroiditis, we have first shown an impaired surge of glucocorticoid hormones after stimulation of the HPA axis by antigens or certain cytokines (glucocorticoid-increasing factors--GIFs). More recently, we have found a similar behavior in models with systemic autoimmune diseases, that is, murine lupus erythematosus and avian scleroderma. More detailed studies have, however, proven that the mechanisms underlying this altered immuno-endocrine communication via the HPA axis differs in different models. Finally, recent data point to the possibility that the classical pathways of glucocorticoid-T-cell interactions also take place in the thymus itself, which has been shown to be a site of steroid hormone production.
 ...
PMID:Neuroendocrine-immune disturbances in animal models with spontaneous autoimmune diseases. 962 86

Microbial DNA has multiple immune effects including the capacity to induce polyclonal B cell activation and cytokine production in normal mice. We recently described the accelerated induction of anti-DNA Abs in NZB/NZW mice immunized with Escherichia coli (EC) dsDNA; paradoxically these mice developed less renal disease than unimmunized mice or mice immunized with calf thymus DNA. We postulated that alterations in cytokine production induced by bacterial DNA may play a key role in renal protection. To determine the effect of bacterial DNA on cytokine production in NZB/NZW mice, we measured the serum cytokine levels, cell culture supernatant cytokine levels, and number of cytokine-producing splenocytes in NZB/NZW mice injected with EC DNA, calf thymus DNA, or an immune active oligonucleotide. There was a 10- to 25-fold increase in the number of cells secreting IFN-gamma compared with IL-4 in mice immunized with EC DNA. IL-12-secreting cells were also increased by bacterial DNA immunization. In parallel with the increase in IFN-gamma secreting cells, there was a significant rise in serum IFN-gamma levels in mice receiving EC DNA. These results indicate that EC DNA modulates systemic cytokine levels in NZB/NZW mice, selectively increasing IL-12 and IFN-gamma while decreasing IL-4 production. The cytokine response of NZB/NZW mice to bacterial DNA may be of significance in disease pathogenesis and relevant to the treatment of lupus-like disease.
 ...
PMID:Effects of bacterial DNA on cytokine production by (NZB/NZW)F1 mice. 978 Jan 54

Lupus-prone mice develop a systemic autoimmune disease that is dependent upon the B cell help provided by autoreactive alphabeta CD4+ T cells. Since autoreactive T cells with high affinity for self peptides are normally deleted in the thymus, their presence in these mice suggests the possibility that intrathymic negative selection may be defective. Here, we directly compared central T cell tolerance in response to a conventional peptide Ag in lupus-prone MRL/MpJ mice with a nonautoimmune strain using an MHC class II-restricted TCR transgene. Our results did not demonstrate any defects after Ag exposure in the induction of intrathymic deletion of immature CD4+ CD8+ thymocytes, in TCR down-regulation, or in the number of apoptotic thymocytes in MRL/MpJ compared with nonautoimmune mice. Furthermore, we found that the lpr mutation had no influence upon the Ag-induced thymic deletion of immature thymocytes. These data support the notion that T cell autoreactivity in MRL/MpJ mice is caused by defects in peripheral control mechanisms.
 ...
PMID:Central T cell tolerance in lupus-prone mice: influence of autoimmune background and the lpr mutation. 983 35


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>