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)

The active vitamin D metabolite, 1,25-dihydroxyvitamin D3[1,25-(OH)2D3], exerts immunosuppressive activity. At a cellular and molecular level, the hormone preferentially targets helper T cell activity (Th1) by inhibiting the secretion of both IL-2 and IFN-gamma by Th1 and by suppressing the secretion pro-Th1 cytokine IL-12 by antigen-presenting cells. The active metabolite further inhibits class II antigen expression and enhances suppressor cell activity. In animal models of autoimmunity, 1,25-(OH)2D3 prevents the development of experimental autoimmune encephalomyelitis, reduces the incidence of diabetes, and attenuates murine lupus. The hormone also prolongs graft survival in animal models of transplantation. In humans, non-classical use of 1,25-(OH)2D3 has led to an anti-proliferative effect in psoriasis, antineoplastic effect in prostate cancer, and immunomodulatory effect in scleroderma. The development of less hypercalcemic analogs might open a new therapeutic area for vitamin D3.
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PMID:1,25-Dihydroxyvitamin D3--a hormone with immunomodulatory properties. 1076 31

The aim of our review is to summarize common genetic variations of some receptors associated with clinical consequences, which were not outlined in the previous special issue of this journal. Because of the multiple pathomechanisms of diseases, a set of genetic variation can play a role in the development of pathological conditions. From the data available three articles would merit a greater interest. In systemic lupus erythematosus the associations related to some polymorphisms of Fc-, tumor necrosis factor (TNF) alpha- and interferon receptor may explore new autoimmunological and inflammatorical pathomechanisms. In the endocrinology, the androgen receptor repeat polymorphism will exert significant aspects in the development of prostate cancer. The pleoitropic responsibility of vitamin D3 receptor polymorphism in the pathogenesis of immunological disorders (primary biliary cirrhosis, inflammatory bowel disease, type 1 diabetes mellitus) and of malignancies (malignant melanoma, breast cancer) shed light on the importance of common nuclear receptors. Nevertheless, in the future studies a more consistent approach minimizing requirement bias in the selection of patients will approve our understanding the role of genetic influence on the pathogenesis of diseases.
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PMID:Receptor polymorphisms and diseases. 1123 Sep 90

The objective of this study was to identify all malignancies in an inception cohort of SLE patients in southern Sweden and compare with the observed frequencies and spectrum of malignancies in the general population. All adult incidence cases of SLE in a defined population during the period 1981-1996 were retrieved from a prospective database and the cases were followed to endpoint or through 1998. The SLE cohort registry was aggregated with the National Cancer Registry to identify all malignancies by date, type and outcome. Standardized morbidity rates (SMR) were calculated based on the sex- and age-matched general population of the region. Sixteen malignancies occurred in 13 patients out of a total of 116 SLE patients observed for 1086 patient-years. The SMR for all cancers detected was 2.24 (confidence interval 0.6-5.7) for males and 1.02 (confidence interval 0.4-2.1) for females and thus indicative of no general increase in malignancies. However, the SMR for non-Hodgkin lymphoma was 11.63 (confidence interval 1.4-42.0), for pulmonary cancer 5.55 (confidence interval 0.7-20.1) and prostatic cancer 6.41 (confidence interval 1.3-18.7) all significantly increased. The increase in prostatic carcinoma disappeared when only cases occurring after a latency period of 3y after SLE diagnosis were included. In this comprehensive inception cohort of SLE no increase in relative risk of malignancy overall was found, but the frequencies of non-Hodgkin lymphoma and pulmonary cancer were increased, possibly also the frequency of prostatic carcinoma.
Lupus 2001
PMID:Malignancies during follow-up in an epidemiologically defined systemic lupus erythematosus inception cohort in southern Sweden. 1148 Aug 49

1alpha,25-Dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], the active metabolite of vitamin D(3), is known for the maintenance of mineral homeostasis and normal skeletal architecture. However, apart from these traditional calcium-related actions, 1,25-(OH)(2)D(3) and its synthetic analogs are being increasingly recognized for their potent antiproliferative, prodifferentiative, and immunomodulatory activities. These actions of 1,25-(OH)(2)D(3) are mediated through vitamin D receptor (VDR), which belongs to the superfamily of steroid/thyroid hormone nuclear receptors. Physiological and pharmacological actions of 1,25-(OH)(2)D(3) in various systems, along with the detection of VDR in target cells, have indicated potential therapeutic applications of VDR ligands in inflammation (rheumatoid arthritis, psoriatic arthritis), dermatological indications (psoriasis, actinic keratosis, seborrheic dermatitis, photoaging), osteoporosis (postmenopausal and steroid-induced osteoporosis), cancers (prostate, colon, breast, myelodysplasia, leukemia, head and neck squamous cell carcinoma, and basal cell carcinoma), secondary hyperparathyroidism, and autoimmune diseases (systemic lupus erythematosus, type I diabetes, multiple sclerosis, and organ transplantation). As a result, VDR ligands have been developed for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism. Furthermore, encouraging results have been obtained with VDR ligands in clinical trials of prostate cancer and hepatocellular carcinoma. This review deals with the molecular aspects of noncalcemic actions of vitamin D analogs that account for the efficacy of VDR ligands in the above-mentioned indications.
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PMID:Noncalcemic actions of vitamin D receptor ligands. 1579 98

Secondary osteoporosis is common among patients being evaluated for osteoporosis. All men and premenopausal women with unexplained bone loss or a history of a fragility fracture should undergo a work-up for secondary osteoporosis. Also, postmenopausal women with risk factors for secondary osteoporosis should be carefully evaluated. The evaluation should include a thorough history, physical examination, bone mineral density testing, and laboratory testing. While there is no consensus for a cost-effective laboratory evaluation, some recommendations include: 25-hydroxyvitamin D, parathyroid hormone (PTH), serum and urine calcium, phosphate, creatinine, liver function tests, a complete blood count, testosterone in men, and thyroid-stimulating hormone. After a thorough review of the evaluation for secondary osteoporosis, this chapter reviews the pathophysiology and treatment of secondary osteoporotic disorders, including vitamin D insufficiency, osteomalacia, the osteoporosis of erosive inflammatory arthritis, ankylosing spondylitis, systemic lupus erythematosus, and osteoporosis related to anti-androgenic therapy for prostate cancer and aromatase inhibitor therapy for breast cancer. Physicians have a significant responsibility to evaluate and treat the underlying medical problem that is the cause of secondary osteoporosis and to optimize bone health in the individual patient.
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PMID:The management of secondary osteoporosis. 1630 Nov 95

The erythrocyte sedimentation rate (ESR) is a time-honored blood test, which assesses the degree of erythrocyte aggregation by acute phase proteins such as fibrinogen and immunoglobulins. Various intrinsic factors may influence the ESR, among them polycytemia, microcytosis or fibrinogen consumption lead to a decreased ESR, while anemia, macrocytosis or hypoalbuminemia lead to an increased ESR. The ESR still is a very valid test for the diagnosis of certain chronic diseases (polymyalgia, rheumatoid arthritis, multiple myeloma, septic arthritis and ostemyelitis) and the follow-up of certain chronic diseases (polymyalgia rheumatica, systemic lupus erythematodes, chronic infections, prostatic cancer, and Hodgkin's disease). In acute disease states and their monitoring C-reactive protein and eventually procalcitonin are the tests of choice. The ESR should not be used for screening and check-up examinations in asymptomatic patients.
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PMID:[Erythrocyte sedimentation rate--more than an old fashion?]. 1645 Jul 41

Three very recent reports provide convincing statistical evidence (P < 10(-8)), at a genome-wide level, of the association of common polymorphisms with three different common diseases: systemic lupus erythematosus (IRF5), prostate cancer and type 1 diabetes (IFIH1 region). This adds to the trickle--soon to be a flood--of disease association results that are highly unlikely to be false positives. There are other convincing examples in the last 12 months: age-related macular degeneration (CFH), type 1 diabetes (IL2RA, also known as CD25) and type 2 diabetes (TCF7L2). Given 20 years of a literature full of irreproducible results, what has changed?
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PMID:Statistical false positive or true disease pathway? 1732 72

Dehydroepiandrosterone and dehydroepiandrosterone-sulfate are precursors of androgens and estrogens, support the gonadal sexual steroid production. The levels of dehydroepiandrosterone and dehydroepiandrosterone-sulfate are maximal between the ages of 20 and 30 years, then start a decline of 2% per year, leaving a residual of 10-20% of the peak production by the eight decade of life. The age-associated decrease may lead to osteoporosis, deterioration of lipid-metabolism, cardiovascular diseases and second type of diabetes mellitus. Decreased levels were found in autoimmune diseases and in sexual dysfunction, too. Intracrinology describes the formation of active hormones which exert their action in the same cells where synthesis took place without release into the pericellular compartment. The high local androgen and estrogen concentration may be important in the pathomechanism of hirsutism, acne, seborrhea, breast and prostate cancer. Administration of dehydroepiandrosterone resulted in a reduction of postmenopausal osteoporosis, also the decreased symptoms in systemic lupus erythematosis, psychiatric diseases and sexual disfunction. The authors summarize the metabolism of dehydroepiandrosterone and dehydroepiandrosterone-sulfate and their role in different diseases.
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PMID:[Significance of dehydroepiandrosterone and dehydroepiandrosterone sulfate in different diseases]. 1740 38

Recent large-scale genome-wide association (GWA) studies of SNP variations captured many thousands individual genetic profiles of H. sapiens and facilitated identification of significant genetic traits which are highly likely to influence the pathogenesis of several major human diseases. Here we apply the integrative genomics principles to interrogate relationships between structural features and gene expression patterns of disease-linked SNPs, microRNAs and mRNAs of protein-coding genes in association to phenotypes of 15 major human disorders, namely bipolar disease (BD); rheumatoid arthritis (RA); coronary artery disease (CAD); Crohn's disease (CD); type 1 diabetes (T1D); type 2 diabetes (T2D); hypertension (HT); ankylosing spondylitis (AS); Graves' disease (autoimmune thyroid disease; AITD); multiple sclerosis (MS); breast cancer (BC); prostate cancer (PC); systemic lupus erythematosus (SLE); vitiligo-associated multiple autoimmune disease (VIT); and ulcerative colitis (UC). We selected for sequence homology profiling a set of approximately 250 SNPs which were unequivocally associated with common human disorders based on multiple independent studies of 220,124 individual samples comprising 85,077 disease cases and 129,506 controls. Our analysis reveals a systematic primary sequence homology/complementarity-driven pattern of associations between disease-linked SNPs, microRNAs and protein-coding mRNAs defined here as a human disease phenocode. We utilize this approach to draw SNP-guided microRNA maps of major human diseases and define a consensus disease phenocode for fifteen major human disorders. A consensus disease phenocode comprises 72 SNPs and 18 microRNAs with an apparent propensity to target mRNA sequences derived from a single protein-coding gene, KPNA1. Each of microRNAs in this elite set appears linked to at least three common human diseases and has potential protein-coding mRNA targets among the principal components of the nuclear import pathway. We confirmed the validity of our findings by analyzing independent sets of most significant disease-linked SNPs and demonstrating statistically significant KPNA1-gene expression phenotypes associated with human genotypes of CD, BD, T2D and RA populations. Our analysis supports the idea that variations in DNA sequences associated with multiple human diseases may affect phenotypes in trans via non-protein-coding RNA intermediaries interfering with functions of microRNAs and defines the nuclear import pathway as a potential major target in 15 common human disorders.
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PMID:An SNP-guided microRNA map of fifteen common human disorders identifies a consensus disease phenocode aiming at principal components of the nuclear import pathway. 1871 69

Thymomas are rare tumors of the mediastinum; a limited number of small studies have evaluated the outcomes in these patients. We identified 668 patients with thymoma from the Swedish Cancer Registry, and 2,719 population-based matched controls. We obtained information on autoimmunity from the nationwide inpatient/outpatient hospital discharge Registry. We constructed Kaplan-Meier curves for survival analysis, conditional regression and Cox proportional hazards models to evaluate the association between thymoma and autoimmune diseases, and standardized incidence ratios (SIRs) to evaluate the risk for second cancers following thymoma. Compared with controls, patients with benign or malignant thymoma had a poorer (p < 0.001) 5-year (79%, 53% vs. 91%), 10-year (65%, 39% vs. 78%) and 20-year (43%, 18% vs. 55%) overall survival. For thymoma patients, younger age at diagnosis and being diagnosed in recent years were associated with a better survival. Compared with controls, thymoma patients were more likely to have an autoimmune disease at some point during their lives (32.7% vs. 2.4%, respectively, p < 0.001), most frequently myasthenia gravis (24.5%), systemic lupus erythematosus (2.4%) and red cell aplasia (1.2%). Thymoma patients had twofold excess risk for second cancers compared with the general population, most notably: non-melanoma skin cancer (SIR = 10.6, 95% confidence intervals (CI) = 6.0-17.3), non-Hodgkin lymphoma (SIR = 6.8, 95% CI = 3.00-13.0), and cervical (SIR = 6.9, 95% CI = 1.4-20.1), endocrine (SIR = 4.7, 95% CI = 1.3-12.0), and prostate cancer (SIR = 3.0, 95% CI = 1.7-4.8). Despite the improved survival for thymoma patients over time, they have worse survival than controls. Thymoma patients are in need for follow-up to detect and manage autoimmune diseases and cancer.
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PMID:A population-based assessment of mortality and morbidity patterns among patients with thymoma. 2066 26


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