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)

Acquired von Willebrand syndrome (AVWS) associated with hypothyroidism is of type I, results from a decreased synthesis of factor VIII and von Willebrand factor (VWF), responds to desmopressin with normal half-life times for factor VIII and VWF parameters, and disappears after treatment with I-thyroxine. AVWS type I or III, which occurs in a minority of patients with Wilms' tumour in the complete absence of an inhibitor against VWF and no absorption of factor VIII or VWF onto nephroblastoma cells, responds to chemotherapy and/or tumour resection. Hyaluronic acid produced by nephroblastoma cells may be the causative factor in atypical AVWS in Wilms' tumour. AVWS associated with thrombocythaemia of various myeloproliferative disorders is characterized by normal factor VIII and von Willebrand factor antigen (VWF: Ag) levels and a selective deficiency of functional ristocetin co-factor activity (VWF: RCo) and collagen-binding activity (VWF: CBA). AVWS type II in thrombocythaemia is caused by a platelet-dependent proteolysis of large VWF multimers, given the inverse relationship between platelet count and large VWF multimers in plasma and specific increases in the number of proteolytic VWF fragments in plasma. The laboratory findings of AVWS associated with systemic lupus erythematosus or IgG benign monoclonal gammopathy are characterized by a prolonged bleeding time and activated partial thromboplastin time, decreased or absent ristocetin-induced platelet activity, low to very low levels of factor VIII coagulant activity (mean 15%), VWF: Ag (mean 10.7%) and VWF: RCo (mean 6.2%), and a type II multimeric pattern of VWF. Neutralizing and non-neutralizing anti-VWF autoantibodies, usually IgG, have been detected in patient plasma either free or tightly bound to the intermediate and high molecular weight VWF factor VIII particles. The bound auto antibody-antigen complex is rapidly cleared from the circulation, resulting in low levels of factor VIII, VWF parameters as documented by a poor response to desmopressin and VWF factor VIII concentrate. High-dose intravenous immunoglobulin transiently corrects the factor VIII coagulant and VWF levels, lasting for a few weeks in AVWS type II associated with systemic lupus erythematosus or IgG benign monoclonal gammopathy. Prednisolone is effective in AVWS associated with autoimmune disorder. Prednisolone and chemotherapy will not affect AVWS associated with IgG benign monoclonal gammopathy because the monoclonal IgG protein remains to act as an anti-VWF autoantibody. An absorption of VWF to malignant cells has been documented in a few patients with various lymphoproliferative disorders or adrenal carcinoma and suggested to result in a depletion of VWF. The clinical picture of AVWS associated with early-stage IgG multiple myeloma, chronic lymphocytic leukaemia or non-Hodgkin's lymphoma without a paraprotein or no detectable underlying disorder is similar to that of AVWS type II in IgG benign monoclonal gammopathy but poorly documented with regard to the underlying immune mechanism of AVWS. The mechanical destruction of large VWF multimers may be of relevance in conditions in which the shear rate of flowing blood is increased, as may occur in cases of aortic stenosis, other heart valve defects or stenosed vessels. Drug-induced AVWS has been described in association with the use of pesticides valproic acid, ciprofloxacin, griseofulvin, tetracycline, thrombolytic agents and hydroxyethyl starch.
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PMID:Acquired von Willebrand syndromes: clinical features, aetiology, pathophysiology, classification and management. 1168 7

The most common nonimmune etiology of acquired von Willebrand syndrome (AvWS) includes hypothyroidism, Wilms' tumor, thrombocythemia, or congenital heart defects, and the use of various drugs. AvWS type 1 in patients with hypothyroidism is due to decreased Willebrand factor (vWF) synthesis and is reversible by treatment with thyroxin. AvWS type 1 or 3 in children with Wilms' tumor disappears after successful chemotherapy or tumor resection but the mechanism of the vWF deficiency is unknown. The AvWS type 2 in patients with thrombocythemia of various myeloproliferative disorders is caused by increased proteolysis of large vWF multimers at increasing platelet counts to above 1000 x 10 (9)/L. Reduction of platelet counts to normal results in correction of the vWF parameters together with disappearance of the bleeding tendency. Type 2-like AvWS in children with congenital heart valve defects is caused by shear stress-induced proteolysis of large vWF multimers and is reversible after surgical correction. AvWS associated with the use of drugs disappears after discontinuation of the causative agent. Immune-mediated AvWS is associated with either systemic lupus erythematosus (SLE) or immunoglobulin G (IgG) benign monoclonal gammopathy (BMG), and usually shows a type 2 vWF deficiency. Using a simple enzyme-linked immunosorbent assay, an IgG antibody against vWF is detectable in AvWS associated with SLE and IgG BMG. The IgG-autoantibody-factor (F) vWF/VIII complex is rapidly cleared from the circulation, which explains the combined FVIII:coagulant activity (C) and vWF deficiency and the poor responses of FVIII:C and vWF parameters to intravenous desmopressin acetate and vWF/FVIII concentrates. A transient correction of both FVIII:C and vWF parameters to normal for a few weeks after high-dose intravenous immunoglobulin is seen in AvWS associated with SLE and IgG BMG. AvWS associated with SLE uniformly shows a curative response to corticosteroids. AvWS associated with IgG BMG does not respond to corticosteroids, immune suppression, or chemotherapy. AvWS associated with IgM BMG is rare and does not respond to any conventional treatment.
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PMID:Immune-mediated etiology of acquired von Willebrand syndrome in systemic lupus erythematosus and in benign monoclonal gammopathy: therapeutic implications. 1697 68

The globally increasing number of patients with end-stage renal disease urges the identification of molecular pathways involved in renal pathophysiology, to serve as targets for intervention. Moreover, the identification of genetic risk factors or protective genes can aid tailored therapy. Tools that can be used to identify genes involved in renal disease include gene expression arrays, linkage analysis and association studies. Arrays are a powerful and widely used approach to the analysis of gene transcription and protein expression, whereas linkage analysis and association studies link disease susceptibility to particular genetic regions. Animal models are available to pinpoint the disease-associated genes. Candidate genes so far identified in renal disease include those encoding the podocyte proteins nephrin and podocin, the transcription factor WT1, the calcium channel TRPC6 and the enzyme phospholipase C-epsilon-1 (in congenital nephrotic syndrome and focal segmental glomerulosclerosis), and carnosinase (in diabetic nephropathy). In addition, linkage studies have identified chromosomal regions implicated in systemic lupus erythematosus, diabetic nephropathy and familial IgA nephropathy. Future studies will elucidate the emerging role of epigenetic regulation of gene expression in renal disease.
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PMID:Primer: strategies for identifying genes involved in renal disease. 1836 21

Normal human physiology is dependent on a tight control of the fasting blood glucose (FBG) levels. The islets of pancreas maintains FBG levels within a narrow range of 4-6mmol/L by secreting various hormones, especially insulin and glucagon. However, the hormone secretions by the islets of pancreas are governed by a collective effort among pancreas-islet axis, brain-islet axis, liver-islet axis, gut-islet axis, and adipocyte/myocyte-islet axis. Furthermore, the damage of pancreas, vascular system, brain, liver, intestine, adipose, muscle, and other organs and tissues might affect FBG levels through insulin resistance or impaired insulin signaling, which is the hallmark of type 2 diabetes. In this study, 320,572 clinical lab test results of FBG levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed. Based on the mean (SD), median, and p (-Log10p) values, we found 57/64 diseases including type 2 diabetes, pancreatitis, diabetic nephropathy, and pancreatic cancer had significantly (p<0.05, -Log10p>1.30) increased whereas 6/64 diseases including preeclampsia, Wilms' tumor, and lupus erythematous had significantly decreased FBG levels compared to that of healthy controls. These data indicated that the increased FBG levels might be a general pathophysiological property of diseased tissues or organs and the increased FBG levels might be a consequence but not the cause for either prediabetes or type 2 diabetes.
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PMID:Fasting blood glucose levels in patients with different types of diseases. 3090 57

Renal neoplasia occurring as a second malignancy following childhood cancer has been most closely associated with neuroblastoma and Wilms tumor. While some cases have been associated with a genetic predisposition, nearly all are thought to result from "late effects" of therapy-related toxicity that involves chemotherapy or radiation. It is unclear if these tumors are enriched for specific molecular or morphologic characteristics. A query of our institutional nephrectomy registry of 8295 patients for renal neoplasia occurring post-treatment for childhood cancer revealed 6 patients with Wilms tumor, 4 with neuroblastoma, and 1 with acute lymphoblastic leukemia (ALL). Three additional cases of MiT family translocation renal cell carcinoma (RCC), from 2 patients, following chemotherapy for neuroblastoma and systemic lupus erythematosus and another of clear cell RCC post-ALL were included. The most common tumor type was clear cell RCC: 9/19 cases (47.4%), followed by metanephric adenoma and MiT family translocation RCC (3/19, 15.8%). There were no characteristic features to indicate a unique renal neoplasia subtype. Potential syndromic renal neoplasia occurred in 2 patients, metanephric adenomas and oncocytoma in a patient with hyperparathyroidism-jaw tumor syndrome post-treatment of Wilms tumor and a fumarate hydratase-deficient RCC in a patient post-treatment for ALL. The mean age at diagnosis of childhood neoplasia or treatment with chemotherapy or radiation was 4.7 years, and the average time to subsequent renal neoplasia was 31 years. Five (of 14) patients developed metastatic RCC, and there were 2 RCC-related deaths. These results indicate the need for extended clinical follow-up of these patients.
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PMID:Secondary renal neoplasia following chemotherapy or radiation in pediatric patients. 3268 44