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

In a number of skin disturbances conditioned or aggravated by sunlight and/or mainly diffused to the cutaneous connective tissue (present acquired pellagra, lupus erythematosus, porphyria cutanea tarda, actinic reticuloid, Rothmund-Thomson syndrome, lymphocytoma cutis, scleroderma, dermatomyositis, burns, linphomas, parapsoriasis, acrodermatitis enteropathica) excretive changes were found only in the "via kynurenine" metabolites. As a rule kynureniase activity was reduced and tryptophan-pyrrolase activity was increased. In the epidermis tryptophan leads to niacin pathway was found to be present and sometimes autonomous.
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PMID:Tryptophan metabolism in skin diseases. 124 86

The iatrogenic L-tryptophan-induced eosinophilia-myalgia syndrome, often considered to be a "new" disease, has proven to be a remarkable mimic of the classic sclerosing rheumatologic disorders. Although subacute cutaneous lupus erythematosus remains a clinically defined entity, supportive histologic and immunopathologic findings have recently been proposed. Rheumatoid neutrophilic dermatitis needs to be added to our usual differential diagnosis of a neutrophilic dermatosis without leukocytoclastic vasculitis. The antiphospholipid syndrome is associated with noninflammatory vascular thrombosis and often has recognizable cutaneous findings. Finally, ANCA are a valuable adjunct in the systemic evaluation of patients with vasculitis syndromes and suggest a common pathogenesis for several of the systemic vasculitides.
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PMID:Collagen vascular disease. 173 Jan 64

Early in the course of studies of the Spanish toxic oil syndrome it was recognized that vascular lesions were a major problem, most logically attributable to endothelial damage by the toxic oil. However, most clinical attention has been directed to the pulmonary complications and the evolution into a scleroderma-like illness later. In this study of 11 victims of the toxic oil syndrome careful postmortem studies of the coronary arteries and conduction system and neural structures of the heart demonstrated major injury to all those components of the heart. Obliterative fibrosis of the sinus node in four cases resembled findings in fatal scleroderma heart disease, and in eight the cardiac lesions resembled those of lupus erythematosus. The more impressive pathologic features involved the coronary arteries and neural structures, which were abnormal in every heart. The arterial disease included widespread focal fibromuscular dysplasia, but there was also an unusual myointimal proliferative degeneration of both small and large coronary arteries in five patients, four of whom were young women. In two hearts, portions of the inner wall of the sinus node artery had actually detached and embolized downstream. Coronary arteritis was rarely found. Inflammatory and noninflammatory degeneration of cardiac nerves was widespread. Fatty infiltration, fibrosis and degeneration were present in the coronary chemoreceptor. In most respects these cardiac abnormalities resemble those described in the eosinophilia-myalgia syndrome caused by an altered form of L-tryptophan. In both diseases there is good reason to anticipate more clinical cardiac difficulties than have so far been reported, and even more basis for future concern, especially relative to coronary disease and cardiac electrical instability.
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PMID:Cardiac abnormalities in the toxic oil syndrome, with comparative observations on the eosinophilia-myalgia syndrome. 191 15

The prescription drugs procainamide (PA) and hydralazine (HYD) are associated with the induction of autoimmunity and a clinical syndrome called drug-induced lupus. Since PA- and HYD-induced autoantibodies are directed primarily against histones and histones are prime acceptors of poly (ADP-ribose) (PADPR), we have investigated the effects of PA and HYD on the activity of poly (ADP-ribose) polymerase (PADPRP). Control substances, with structures similar to PA and HYD but not known to induce lupus, included N-acetylprocainamide (NAPA) and the amino acids phenylalanine, tryptophan and proline, and their amide derivatives. Wil-2 cells were incubated in 0.5-50 microM PA, NAPA and HYD, which included therapeutic concentrations of these drugs. The mean enhancement of incorporation of [3H]-nicotinamide adenine dinucleotide (NAD) into PADPR was 1.84 (P = 0.005) with PA, with HYD 1.48 (P = 0.029), and with NAPA 1.38 (P = 0.036). This increase was suppressed by 3-aminobenzamide, an inhibitor of PADPRP activity. Little or no increase in [3H]-NAD incorporation was observed with equivalent concentrations of phenylalanine, phenylalaninamide or tryptophan. However, a 1.29-fold increase was noted with 0.5 microM tryptophanamide, a 1.26-fold increase with 0.5 microM prolinamide and a 1.4-fold increase with 50 microM proline. PA increased PADPRP activity in B- and T-cell lines but not in promyelocytic leukemia or epithelial cell lines. Since poly (ADP-ribosylation) is important in the cellular response to various agents, the increased ADP-ribosylation of intracellular molecules may be a key event in the induction of autoantibodies.
Lupus 1993 Jun
PMID:Effect of procainamide and hydralazine on poly (ADP-ribosylation) in cell lines. 769 Feb 94

Patients with systemic lupus erythematosis (SLE) often manifest features of other autoimmune diseases. In this review, we provide a detailed compendium of features of SLE that overlap with other conditions. This compendium is important because a critical feature in our understanding of autoimmunity has been the clustering of coexisting/different autoimmune diseases both within an affected patient and within a pedigree. Indeed, autoimmune disorders share a variety of similar clinical and serological defects. For example, all autoimmune disorders are associated with the elaboration of autoantibodies and/or the production of self-reactive mononuclear cell populations; many have high levels of immune complexes and defects in cell-mediated immunity. Several diseases share similar genetic backgrounds, as reflected by study of loci within the major histocompatibility complex. In part the coassociation is due to common genetic tendencies with different environmental precipitating agents (trigger mechanisms). It is likely that many factors can modulate the immune system to autoimmunity in the presence of an appropriate genetic background, eg, drugs, viral infections, UV irradiation, and toxins, ie, toxic oil syndrome and L-tryptophan-induced eosinophilic myalgia. The coexistence of SLE with other autoimmune diseases is an excellent venue to understand these events, and we believe that the presence of other autoimmune diseases in patients with SLE can be called the kaleidoscope of autoimmunity.
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PMID:The coexistence of systemic lupus erythematosus with other autoimmune diseases: the kaleidoscope of autoimmunity. 783 52

The cause of toxic oil syndrome (TOS) has not yet been definitively determined, but some genetic susceptibility factors (certain HLA antigens and female sex) have been identified in 236 patients. Similarities with genetic factors for scleroderma and hydralazine-induced lupus (i.e. in TOS female sex and HLA-A24, Pcorrected = 0.00001 and DR4, Pcorrected = 0.04, respectively) may provide a clue to the responsible xenobiotic and its pathogenesis, and may also help in understanding the basis of the related eosinophilia-myalgia syndrome associated with tryptophan ingestion. In this paper it is also established that a human class I antigen (HLA-A24) and, independently, an HLA class II haplotype (DR4-DQ8, Pcorrected = 0.04) and arginine 52 in the alpha-DQ chains (Pcorrected = 0.03) are associated with TOS susceptibility, similarly to insulin-dependent diabetes. This further supports the classification of TOS as an autoimmune disease. Also, the increased frequency of a particular set of low-frequency HLA class I antigens in chronic TOS patients (i.e. B27, B37, B38 and B49) and the probable decrease in the frequency of HLA-B homozygotes in surviving patients (Pcorrected = 0.008) may provide an objective model to explain the maintenance of the HLA polymorphism: less frequent HLA alleles may be more advantageous in the event of unexpected human contact with unusual xenobiotics (not only microbes); however, other mechanisms working together to preserve and generate HLA polymorphism may coexist.
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PMID:Frequencies of HLA-A24 and HLA-DR4-DQ8 are increased and that of HLA-B blank is decreased in chronic toxic oil syndrome. 880 34

Immunoadsorption offers some advantages over plasmapheresis; until recently the primary advantage has been avoidance of substitution fluids. In collagen vascular disorders, immunoadsorption is performed for the same indications as plasma exchange; most often adsorbers with binding capacities for IgG and circulating immune complexes are used. Tested ligands are protein A, anti-IgG antibodies, Clq, phenylalanine, and tryptophan. Human IgG was utilized to adsorb rheumatoid factor and dextran sulfate, DNA, or specific anti-idiotypes for anti-DNA antibodies in systemic lupus erythematous (SLE). Most applications have used immunoadsorbent columns in pretransplantation treatment of patients with high panel reactivity and in patients with idiopathic thrombocytopenic purpura (ITP). For these indications, as for systemic connective tissue diseases, randomized trials have yet to be conducted. SLE controlled trials have been completed for IMPH-350 and Ig-Therasorb. Results indicated excellent biocompatibility and good clinical responses. Using protein A in primary systemic vasculitis, histologically proven inactivation of renal involvement was demonstrated, but the patients were also treated with immunosuppressive drugs. Randomized controlled trials are mandatory to provide continued support to the therapeutical opportunities offered only by immunoadsorption.
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PMID:Immunoadsorption in systemic connective tissue diseases and primary vasculitis. 1022 54

A large number of drugs and an increasing number of environmental agents reportedly result in the appearance of a number of autoantibodies and in many instances in the appearance of a range of autoimmune clinical syndromes. The major disorders so recognized have marked resemblances to the autoimmune disease systemic lupus erythematosus. The commonly used term is drug-induced lupus; a better term is drug-related lupus. There is considerable interest at the present time in an increasing number of environmental agents. There have been two epidemics in recent years--one in Spain to a contaminant of rapeseed oil and one in the United States to a contaminant of l-tryptophan that caused an eosinophilic myositis. It is important for physicians and others involved in health care to recognize the potential associations of these diseases of unknown cause or causes.
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PMID:Are there environmental forms of systemic autoimmune diseases? 1050 35

Environmental and other xenobiotic agents can cause autoimmunity. Examples include drug-induced lupus, toxic oil syndrome, and contaminated l-tryptophan ingestion. Numerous mechanisms, based on (italic)in vitro(/italic) evidence and animal models, have been proposed to explain how xenobiotics induce or accelerate autoimmunity. The majority of these can be divided into three general categories. The first is those inhibiting the processes involved in establishing tolerance by deletion. Inhibiting deletion can result in the release of newly generated autoreactive cells into the periphery. The second mechanism is the modification of gene expression in the cells participating in the immune response, permitting lymphocytes to respond to signals normally insufficient to initiate a response or allowing the antigen-presenting cells to abnormally stimulate a response. Abnormal gene expression can thus disrupt tolerance maintained by suppression or anergy, permitting activation of autoreactive cells. The third is the modification of self-molecules such that they are recognized by the immune system as foreign. Examples illustrating these concepts are presented, and related mechanisms that have the potential to similarly affect the immune system are noted. Some mechanisms appear to be common to a variety of agents, and different mechanisms appear to produce similar diseases. However, evidence that any of these mechanisms are actually responsible for xenobiotic-induced human autoimmune disease is still largely lacking, and the potential for numerous and as yet unidentified mechanisms also exists.
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PMID:Environmentally induced autoimmune diseases: potential mechanisms. 1050 39

The isoprenoid pathway produces three key metabolites--digoxin (membrane Na(+)-K+ ATPase inhibitor, regulator of neurotransmitter transport, and immunomodulatory agent), dolichol (regulatory of N-glycosylation of proteins), and ubiquinone (free-radical scavenger). The pathway was assessed in systemic lupus erythematosis with neuropsychiatric manifestations, slow viral diseases (subacute sclerosing panencephalitis [SSPE], and Creutzfeldt-Jakob disease [CJD]) and patients with recurrent respiratory infections. This was also studied for comparison in patients with right hemispheric and left hemispheric dominance. The isoprenoid pathway was upregulated with increased digoxin synthesis in patients with neurolupus, SSPE, and CJD, and in those with right hemispheric dominance. The tryptophan catabolites were increased and the tyrosine catabolites reduced. In these patients the dolichol and glycoconjugate levels were elevated and lysosomal stability was reduced. The ubiquinone levels were low and free-radical levels increased in these patients. The membrane cholesterol:phospholipid ratios were increased and membrane glycoconjugates reduced. On the other hand, in patients with recurrent respiratory infection and left hemispheric dominance, the reverse patterns and hypodigoxinemia with a downregulated isoprenoid pathway were noticed. The isoprenoid pathway is important in the pathogenesis of neurolupus, CJD, SSPE, and recurrent respiratory infections. Hypothalamic digoxin and chemical hemispheric dominance play an important role in the regulation of immunity.
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PMID:Hypothalamic digoxin, hemispheric dominance, and neuroimmune integration. 1232 97


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