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)

Oxidative stress caused by poor detoxification efficiency of reactive oxygen species (ROS) may play a role in the development of systemic lupus erythematosus (SLE). Glutathione S-transferase (GST) is involved in the detoxification of ROS and genetic polymorphisms of GSTM1, GSTT1 and GSTP1 are associated with altered enzyme activity. The aim of this study was to determine whether GSTMI (deletion), GSTT1 (deletion) and GSTP1 (Ile(105)-->Val(105)) polymorphisms are associated with susceptibility to SLE or frequency of clinical manifestations according to the ACR diagnostic criteria. DNA was isolated from blood samples collected from 330 patients with SLE and 270 age- and sex-matched controls. GST genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. No associations were observed between GSTM1, GSTT1, and GSTP1 genotypes and risk of SLE. Among SLE patients, the GSTM1 null genotype was associated with a lower frequency of hematological disorders (P = 0.012), and a higher SSA(+)/SSB(-) autoantibody profile (P = 0.042). Compared to SLE patients with the GSTT1 non-null genotype, those with the GSTT1 null genotype had a lower frequency of discoid rash (P = 0.018), and nephritis (P = 0.033). Our findings suggest that genetic polymorphisms of GSTM1, GSTT1, and GSTP1 do not influence the risk of SLE, but a deletion of either GSTM1 or GSTT1 may influence certain clinical manifestations of the disease.
Lupus 2005
PMID:Glutathione S-transferase genotype and risk of systemic lupus erythematosus in Koreans. 1593 38

Energy restriction (ER) and dietary fish oil (FO) are known to reduce the severity of glomerulonephritis and increase the lifespan of lupus-prone (NZB x NZW) F1 (B/W) mice. In the present study, mice were fed either ad libitum or energy-restricted (a 40 % lower energy intake than the diet ad libitum), semi-purified diets containing 5 % maize oil or 5 % fish oil supplementation. To estimate the renal damage associated with oxidative stress, the total amounts of reactive oxygen species (ROS), cyclooxygenase-derived ROS and levels of guanidino compounds were measured. Additionally, we assessed the putative action of ER and FO on several key antioxidant enzymes measured in the kidney post-mitochondrial fraction. Results showed that the age-related increase in creatinine level was significantly reduced by ER and FO in old mice. In contrast, arginine and guanidino acetic acid levels showed a decrease with age but were increased by ER and FO. The GSH:GSSG ratio showed a significant decrease with age, whereas ER and FO feeding prevented the decrease. The age-related decrease in antioxidant scavenging superoxide dismutase, catalase and glutathione peroxidase activities were all reversed by ER and FO. The moderately decreased glutathione reductase and glutathione-S-transferase activities with age were significantly increased by ER and FO. Furthermore, the increased total ROS and cyclooxygenase-derived ROS levels were effectively reduced by ER and FO. In conclusion, our data strongly indicate that ER and FO maintain antioxidant status and GSH:GSSG ratio, thereby protecting against renal deterioration from oxidative insults during ageing.
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PMID:Effects of energy restriction and fish oil supplementation on renal guanidino levels and antioxidant defences in aged lupus-prone B/W mice. 1602 52

Engagement of T cell receptors by antigen-presenting cells or stimulation by cytokines determine whether the cell will become activated, anergic or die via apoptosis or necrosis. Ca2+ is a key second messenger that delivers signal from the cell surface, reactive oxygen intermediates and nitric oxide are recently recognized as important mediators of T cell activation. Nitric oxide is a multifunctional intracellular and intercellular messenger induces mitochondrial biogenesis in many cell types, such as lymphocytes. Mitochondria produce reactive oxygen intermediates and store and release Ca2+ in response to activation and death signals. Rapid Ca2+ fluxing is increased while sustained Ca2+ signaling is decreased in lupus T cells. Lupus T cells contain increased numbers and mass of mitochondria. Serum nitric oxide levels and production of nitric oxide by monocytes is increased in patients with systemic lupus erythematosus. Lupus T cells exhibit mitochondrial hyperpolarization and increased mitochondrial mass, which confer predisposition to necrosis rather than apoptosis in response to repetitive activation and death signals. Exposure of normal T cells to nitric oxide dose-dependently increase the mitochondrial mass and mimic rapid and sustained Ca2+ signal abnormalities observed in lupus T cells. Thus increased mitochondrial biogenesis may account for altered Ca2+ handling and represents novel targets for pharmacological intervention in SLE.
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PMID:[Signal transduction abnormalities in systemic lupus erythematosus]. 1615 11

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by various immunologic disorders, including production of autoantibodies, formation of immune complexes, decreased serum complement levels, and lymphocytopenia. One of the hallmarks of this disease is the loss of tolerance to nuclear antigens. The dominant presence of antibodies against the exposed conformational epitopes on chromatin strongly suggests that the pathogenic immune response in lupus is driven by chromatin. In the present study, the binding of SLE autoantibodies with native chromatin and oxygen free radical damaged chromatin was studied. As assessed by direct binding and inhibition ELISA, circulating SLE autoantibodies exhibited a high degree of specificity towards the reactive oxygen species (ROS)-modified chromatin in comparison to native chromatin and this binding specificity was reiterated visually by gel retardation assay. The data suggested possible role of modified chromatin in the induction of SLE autoantibodies and higher recognition of oxidatively damaged chromatin by antibodies in sera of SLE patients. It is indicated that free radical modified chromatin or nucleosomes might be the antigen for the production of circulating autoantibodies in SLE.
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PMID:Binding of circulating SLE autoantibodies to oxygen free radical damaged chromatin. 1627 48

Two-dimensional real-time, M-mode and Doppler echocardiographic measurements were made in 11 adult wolves (Canis lupus) anaesthetised with an intramuscular combination of medetomidine, ketamine, butorphanol and acepromazine followed by isoflurane in oxygen. M-mode measurements of the left ventricle, B-mode measurements of the left atrium and aorta, systolic indices, and Doppler measurements of aortic and pulmonary blood outflow, and of mitral and tricuspid blood inflow, were recorded. The values obtained were compared with those reported for dogs of similar bodyweight and body type. The diastolic measurements of the cardiac chambers and walls were similar to those reported for healthy, conscious dogs, but the use of anaesthesia probably resulted in the markedly different systolic cardiac measurements, systolic indices and Doppler blood flow velocities observed in the wolves. Mild mitral regurgitation, probably due to mitral endocardiosis, was observed in one wolf, and trivial functional mitral insufficiency was observed in five others.
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PMID:Echocardiographic and Doppler echocardiographic findings in 11 wolves (Canis lupus). 1644 38

This case study focuses on the scale-up of a Sp2/0 mouse myeloma cell line based fed-batch bioreactor process, from the initial 3-L bench scale to the 2,500-L scale. A stepwise scale-up strategy that involved several intermediate steps in increasing the bioreactor volume was adopted to minimize the risks associated with scale-up processes. Careful selection of several available mixing models from literature, and appropriately applying the calculated results to our settings, resulted in successful scale-up of agitation speed for the large bioreactors. Consideration was also given to scale-up of the nutrient feeding, inoculation, and the set-points of operational parameters such as temperature, pH, dissolved oxygen, dissolved carbon dioxide, and aeration in an integrated manner. It has been demonstrated through the qualitative and the quantitative side-by-side comparison of bioreactor performance as well as through a panel of biochemical characterization tests that the comparability of the process and the product was well controlled and maintained during the process scale-up. The 2,500-L process is currently in use for the routine clinical production of Epratuzumab in support of two global Phase III clinical trials in patients with lupus. Today, the 2,500 L, fed-batch production process for Epratuzumab has met all scheduled batch releases, and the quality of the antibody is consistent and reproducible, meeting all specifications, thus confirming the robustness of the process.
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PMID:Fed-batch bioreactor process scale-up from 3-L to 2,500-L scale for monoclonal antibody production from cell culture. 1765 76

The need of blood flow to different organs varies rapidly over time which is why there is sophisticated local regulation of blood flow. The term dysregulation simply means that blood flow is not properly adapted to this need. Dysregulative mechanisms can lead to an over- or underperfusion. A steady overperfusion may be less critical for long-term damage. A constant underperfusion, however, can lead to some tissue atrophy or in extreme situations to infarction. Unstable perfusion (underperfusion followed by reperfusion) leads to oxidative stress. There are a number of causes that lead to local or systemic vascular dysregulation. Systemic dysregulation can be primary or secondary of nature. A secondary dysregulation is due to other autoimmune diseases such as rheumatoid arthritis, giant cell arteritis, systemic lupus erythematodes, multiple sclerosis, colitis ulcerosa, or Crohns disease. Patients with a secondary vascular dysregulation normally have a high level of circulating endothelin-1 (ET-1). This increased level of ET-1 leads to a reduction of blood flow both in the choroid and the optic nerve head but has little influence on autoregulation. In contrast, primary vascular dysregulation has little influence on baseline ocular blood flow but interferes with autoregulation. This, in turn, leads to unstable oxygen supply, which seems to be a relevant component in the pathogenesis of glaucomatous optic neuropathy.
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PMID:What is the link between vascular dysregulation and glaucoma? 1799 40

The present aim is to investigate the relationships between aerobic capacity and disease activity, organ damage, health-related quality of life (HRQL) and physical activity in 34 women with systemic lupus erythematosus (SLE) with low-to-moderate disease activity and organ damage. Mean age was 51 (SD 10) years, disease duration 17 (SD 11) years. Aerobic capacity (maximal oxygen uptake/VO2 max) was measured with a bicycle ergometer exercise test. Overall disease activity was assessed with Systemic Lupus Activity Measure (SLAM) and the modified Systemic Lupus Erythematosus-Disease Activity Index (modified SLE-DAI), overall organ damage with the Systemic Lupus International Collaboration Clinics/American College of Rheumatology-Damage Index, [SLICC/(ACR)-DI], HRQL with the 36-item Short-form health-survey (SF-36) and physical activity with a self-assessed question. The women who were low-to-moderately physically active had 89-92% (P < or = 0.001) of VO2 max predicted for sedentary women. Maximal oxygen uptake (L/min, mL/min/kg) correlated to SF-36 physical function (rs = 0.49, rs = 0.72) (P < or = 0.01), but not (rs < or = 0.25) to other HRQL scales, overall disease activity or organ damage or physical activity. The correlation between aerobic capacity and physical function and the absence of correlation between aerobic capacity and physical activity, suggest a possible disease-related factor behind the low aerobic capacity. However, with no correlation between aerobic capacity and overall disease activity and organ damage, low physical activity may contribute to the low aerobic capacity in our sample.
Lupus 2008 Feb
PMID:Aerobic capacity correlates to self-assessed physical function but not to overall disease activity or organ damage in women with systemic lupus erythematosus with low-to-moderate disease activity and organ damage. 1825 Jan 32

Polymorphic light eruption (PLE) is a common skin disease, susceptibility to which is genetically determined. The prevalence of PLE is significantly increased in patients with lupus erythematosus (LE) including subacute cutaneous lupus erythematosus (SCLE) and discoid lupus erythematosus (DLE), which may reflect a common genetic background. Experimental evidence supports a role for reactive oxygen species (ROS) in the pathogenesis of PLE, and the family of glutathione-S-transferase (GST) enzymes exerts a critical physiological role in cellular protection against this oxidative damage. Our aim was to look for association between the functional GST gene polymorphisms and PLE, SCLE, and DLE in a case-control study. The carrier frequency of GSTP1 Val(105) in subjects with PLE was 40%, significantly lower than the carrier frequency in controls (54%, P=0.019), although significance was lost on correction for multiple testing. However, the carrier frequency of the GSTP1 Val(105) allele in combined cutaneous LE (SCLE and DLE) patients with PLE was 42%, significantly lower than in those without PLE (72%), which did survive correction (corrected P=0.043). We have identified evidence supporting a protective GSTP1 allele, the first genetic association to be reported for PLE. This supports a role for ROS in the pathogenesis of PLE and may provide a therapeutic target for future treatment of this common, often disabling, condition.
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PMID:A protective effect of glutathione-S-transferase GSTP1*Val(105) against polymorphic light eruption. 1828 3

We describe a case of systemic lupus erythematosus (SLE) with enteritis and peritonitis who later developed pneumatosis cystoides intestinalis (PCI). A 35-year-old woman with SLE relapsed with enteritis and peritonitis. Prednisolone (PSL) effectively improved her symptoms. However, 6 weeks later, she developed PCI. Tapering of PSL, administration of intravenous cyclophosphamide, prokinetic agents and antibiotics, bowel rest with intravenous hypernutrition therapy and hyperbaric oxygen therapy successfully improved PCI. Although PCI is a rare complication of SLE, the present case suggests that lupus enteritis could be a risk factor for PCI, and that high-dose PSL could cause additional insult to PCI.
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PMID:Pneumatosis cystoides intestinalis following lupus enteritis and peritonitis. 1859 54


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