Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic lupus erythematosus (SLE) lymphocytes failed to accelerate ultraviolet (UV) induced DNA repair synthesis normally observed following inhibition of poly(adenosine diphosphoribose) polymerization. Without inhibitors of poly(adenosine diphosphoribose) polymerase such as nicotinamide or 3-aminobenzamide, DNA repair synthesis following UV irradiation was found to occur normally in the cells of patients. These data suggest that DNA repair is disturbed under special conditions in the lymphocytes of SLE patients.
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PMID:Decrease in the reaction of DNA repair synthesis in response to nicotinamide or 3-aminobenzamide in ultraviolet irradiated systemic lupus erythematosus lymphocytes. 293 21

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

Antiphospholipid antibodies (aPL) are associated with neurological diseases such as stroke, migraine, epilepsy and dementia and are thus associated with both vascular and non-vascular neurological disease. We have therefore examined the possibility that these antibodies interact directly with neuronal tissue by studying the electrophysiological effects of aPL on a brain synaptosoneurosome preparation. IgG from patients with high levels of aPL and neurological involvement was purified by protein-G affinity chromatography as was control IgG pooled from ten sera with low levels of aPL. Synaptoneurosomes were purified from perfused rat brain stem. IgG from the patient with the highest level of aPL at a concentration equivalent to 1:5 serum dilution caused significant depolarization of the synaptoneurosomes as determined by accumulation of the lipophylic cation [3H]-tetraphenylphosphonium. IgG from this patient as well as IgG from two elderly patients with high levels of aPL were subsequently shown to permeabilize the synaptosomes to labeled nicotinamide adenine dinucleotide (NAD) and pertussis toxin-ADP-ribose transferase (PTX-A protein) as assayed by labeled ADP-ribosylation of G-proteins in the membranes. No such effects were seen with the control IgG. aPL may thus have the potential to disrupt neuronal function by direct action on nerve terminals. These results may explain some of the non-thromboembolic CNS manifestations of the antiphospholipid syndrome.
Lupus 1999
PMID:Antiphospholipid antibodies permeabilize and depolarize brain synaptoneurosomes. 1019 7

Hyperhomocysteinaemia is strongly associated with increased relative risk of occlusive vascular disease, mainly of the carotid and coronary arteries. The aim of our study was to assess whether raised plasma homocysteine is a risk factor for thrombotic events in patients with systemic lupus erythematosus (SLE), a condition known to be associated with premature atherothrombotic complications. The study included 34 consecutive consenting SLE patients who were seen in the Rheumatology Unit of Al-Amiri hospital, one of the main teaching hospitals in Kuwait. Twenty consenting healthy subjects were included in the control group. Twenty-four patients were grouped as SLE without thrombosis and 10 had different types of thromboses. Vitamin B(12), folate, anticardiolipin antibodies (IgG and IgM), activated partial thromboplastin time (APTT) and total homocysteine level were measured for both patients and controls. A raised homocysteine concentration was defined as plasma homocysteine level above 9.4 mmol/l. Hyperhomocysteinaemia was found in 21 (61.8%) SLE patients. Low levels of folate and vitamin B(12) were significantly associated with high concentrations of plasma homocysteine (r = -0.35 and -0.39, respectively, P<0.01). SLE patients with elevated homocysteine concentration have a threefold increase in odds ratio of thrombotic events after adjusting for other risk factors (male sex, shortened APTT, treatment with prednisone, low folate and vitamin B(12) levels). We concluded that homocysteine is an independent risk factor for thrombosis in patients with SLE and is potentially modifiable.
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PMID:Hyperhomocysteinaemia and risk of thrombosis in systemic lupus erythematosus patients. 1244 27

The aim of this study is to investigate the role of poly(ADP-ribose) polymerase (PARP), involved in DNA repair and in autoimmune pathologic conditions such as systemic lupus erythematosus (SLE) and both limited systemic sclerosis (lSSc) and diffuse systemic sclerosis (dSSc), to assess its possible implication in the pathogenetic processes. The relationship between PARP activity and the intracellular concentration of its substrate nicotinamide adenine dinucleotide (NAD) is also investigated. Peripheral mononuclear cells (PMC) from controls and patients with SLE, lSSc, and dSSc were irradiated with ultraviolet light (UV) and PARP activity was assayed by a radiochemical method. Pyridine nucleotide concentrations were assayed by a high-performance liquid chromatography-linked method. PARP activity was detectable in nonirradiated cells and showed similar values in all groups. The activity significantly increased after UV irradiation in control, SLE, and lSSc cells, but not in dSSc cells. Irradiated PMC from both SLE and dSSc showed lower enzyme activity with respect to irradiated controls. Higher intracellular NAD content was found in all of the pathologic conditions in comparison to values in the control; this difference was statistically significant in dSSc. Our data demonstrate a lower PARP activity in response to UV damage in PMC from patients affected by the above pathologic conditions compared with controls. An inverse relationship between PARP activity and NAD content was also observed.
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PMID:Poly(ADP-ribose) polymerase activity in systemic lupus erythematosus and systemic sclerosis. 1937 76

Genetic polymorphisms in the endothelial nitric oxide synthase (eNOS) and nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase p22phox are linked with the expression and/or progression of vascular disease. We hypothesized that these polymorphisms may influence the development and/or progression of systemic lupus erythematosus (SLE), given their linkage with vascular disease. DNA from patients with SLE (n = 90) and their age- and sex-matched controls (n = 86) from The Second Xiangya Hospital of Central South University was assessed for eNOS and NADPH oxidase p22phox polymorphisms. These polymorphisms were examined by restriction fragment length polymorphism-polymerase chain reaction. The allele frequency of the NADPH oxidase p22phox gene C242T polymorphisms significantly varied between the SLE patients and the controls. We found no association of the eNOS polymorphism with the development of renal disease. These results indicated that the etiology of patients with SLE is associated with NADPH oxidase p22phox gene C242T polymorphisms. There was no significant increased risk of SLE associated with eNOS polymorphisms in the Chinese population.
Lupus 2010 Feb
PMID:Endothelial nitric oxide synthase and nicotinamide adenosine dinucleotide phosphate oxidase p22phox gene (C242T) polymorphisms and systemic lupus erythematosus in a Chinese Population. 1996 45

Angiostrongylus vasorum is an emerging parasite that is currently distributed through Western Europe and parts of South America. An isolated population is also present in Newfoundland, Canada. This presents a risk of onward spread into North America, but its origin is unknown. To ascertain the phylogeographic relationships and genetic diversity of A. vasorum within the western Palaearctic and eastern Nearctic ecozones, a total of 143 adult and larval nematode specimens were collected from foxes (Vulpes vulpes) and dogs (Canis lupus familiaris) in Canada, Denmark, France, Germany, Ireland, the Netherlands, Portugal and the United Kingdom, and a coyote (Canis latrans) in Canada. DNA was extracted and the second internal transcribed spacer and two mitochondrial loci were amplified and sequenced. Multiple haplotypes (n=35) based on combined mitochondrial sequences (1078bp) of the partial cytochrome oxidase subunit I (COI), large subunit ribosomal RNA (rrnL) and the complete nicotinamide adenine dinucleotide dehydrogenase 3 (NADH3) sequences, were observed throughout the Palaearctic countries sampled; however, only a single haplotype was observed for the Canadian A. vasorum population. The likely origin of A. vasorum in Newfoundland is therefore inferred to be within the western Palaearctic. There was no evidence of genetic segregation of parasites in dogs, foxes and coyotes, supporting the hypothesis that transmission occurs between wild and domestic canids. The transmission dynamics and population structure of this nematode are further discussed.
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PMID:Elucidating the spread of the emerging canid nematode Angiostrongylus vasorum between Palaearctic and Nearctic ecozones. 2013 34

Toll-like receptors are a group of glycoproteins located mostly in cellular membranes, capable of recognizing certain molecules in exogenous microorganisms and initiating immune responses against them through the activation of several intracellular signaling pathways. Toll-like receptors can be stimulated when an inflammatory reaction is needed for the treatment of conditions, such as viral infections or skin cancer, or can be inhibited when a reduction of inflammation is necessary for the treatment of conditions, such as rheumatoid arthritis, systemic lupus erythematosus, and septic shock. In the human skin, keratinocytes and Langerhans cells are known to express these receptors. Skin conditions where Toll-like receptors are known to be upregulated include acne, psoriasis, atopic dermatitis, syphilis, leprosy, Staphylococcus aureus infections, candidiasis, and herpes simplex and varicella zoster infections. Besides imiquimod, which is the most successful and more studied topical Toll-like receptor-modulating agent to date, other topical agents, such as nicotinamide, all-trans retinoic acid, adapalene, zinc, and sodium tosylchloramide, have also been found to exert some of their action through Toll-like receptors. Recent topical agents, including CBT-SL5 and CpG-ODN, are being evaluated for the treatment of inflammatory acne and skin cancer, respectively, and have demonstrated to be effective in the treatment of those conditions.
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PMID:The Expression of Toll-like Receptors in Dermatological Diseases and the Therapeutic Effect of Current and Newer Topical Toll-like Receptor Modulators. 2087 21

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of tolerance to self nucleic acids. The source of autoantigen that drives disease onset and progression is unclear. A candidate source of autoantigen is the neutrophil extracellular trap (NET), which releases nucleic acids into the extracellular environment, generating a structure composed of DNA coated with antimicrobial proteins. On the basis of in vitro and patient correlative studies, several groups have suggested that NETs may provide lupus autoantigens. The observation that NET release (NETosis) relies on activity of the phagocyte NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase (Nox2) in neutrophils of both humans and mice provided a genetic strategy to test this hypothesis in vivo. Therefore, we crossed an X-linked nox2 null allele onto the lupus-prone MRL.Fas(lpr) genetic background and assessed immune activation, autoantibody generation, and SLE pathology. Counter to the prevailing hypothesis, Nox2-deficient lupus-prone mice had markedly exacerbated lupus, including increased spleen weight, increased renal disease, and elevated and altered autoantibody profiles. Moreover, heterozygous female mice, which have Nox2 deficiency in 50% of neutrophils, also had exacerbated lupus and altered autoantibody patterns, suggesting that failure to undergo normal Nox2-dependent cell death may result in release of immunogenic self-constituents that stimulate lupus. Our results indicate that NETosis does not contribute to SLE in vivo; instead, Nox2 acts to inhibit disease pathogenesis, making this enzyme an important target for further study and a candidate for therapeutic intervention.
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PMID:NADPH oxidase inhibits the pathogenesis of systemic lupus erythematosus. 2314 5

C57BL/6 mice bearing the Sle2(z) lupus-susceptibility congenic interval on chromosome 4 display high titers of polyclonal autoantibodies with generalized B cell hyperactivity, hallmarks of systemic lupus erythematosus. In B6.Sle2(z)HEL(Ig).sHEL BCR-transgenic mice, Sle2(z) did not breach central tolerance, but it led to heightened expression of endogenous Ig H and L chains in splenic B cells, upregulation of RAG, and serological polyreactivity, suggestive of excessive receptor revision. Fatty acid amide hydrolase (FAAH), a gene in the minimal subcongenic interval generated through recombinant mapping, was found to be upregulated in Sle2(z) B cells by microarray analysis, Western blot, and functional assays. Pharmacological inhibition of FAAH reversed the increase in receptor revision, RAG expression, and polyreactive autoantibodies in lupus-prone mice. These studies indicate that increased peripheral BCR revision, or selective peripheral expansion of BCR-revised B cells, may lead to systemic autoimmunity and that FAAH is a lupus-susceptibility gene that might regulate this process.
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PMID:Fatty Acid Amide Hydrolase Regulates Peripheral B Cell Receptor Revision, Polyreactivity, and B1 Cells in Lupus. 2677 43


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