Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin D signaling is dependent on the availability and turnover of the active Vitamin D receptor (VDR) ligand 1,25-dihydroxycholecalciferol and on the efficiency of VDR transactivation. Activating and inactivating secosteroid metabolizing p450 enzymes, e.g. 25-hydroxylases, 1alpha-hydroxylase and 24-hydroxylase, are responsible for ligand availability on the basis of substrate production in the skin and of nutritional intake of precursors. Net availability of active hormone depends on the delivery of substrate and the balance of activating and inactivating enzymes. 1Alpha-hydroxylase is the critical activating enzyme. It is expressed in the kidney for systemic supply and in target tissues for local secosteroid activation. It is upregulated in the kidney by low calcium intake and parathyroid hormone, downregulated by phosphatonins and proinflammatory signal transduction. Transactivation of VDR depends on the correct molecule structure, effective nuclear translocation and the presence of the unliganded heterodimer partner retinoid X-receptor (RXR) and other nuclear cofactors. Rapid Vitamin D-dependent membrane associated effects and consecutive second messenger activation exert an own pattern of gene regulation. A membrane receptor for these effects is hypothesized but not yet identified. Rickets is the long known clinical syndrome of impaired Vitamin D signaling due to Vitamin D3 deficiency. It can be caused by inherited defects of the cascade, nutritional deficits, lack of sunlight exposure, malabsorption and underlying diseases like chronic inflammation. It has been shown during the last decades that many modifiers of Vitamin D signaling are targets of disease in terms of inherited and acquired syndromes and that Vitamin D signaling is modulated at multiple levels and is more complex than mere mechanistic ligand/receptor/DNA interaction.
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PMID:Vitamin D signaling is modulated on multiple levels in health and disease. 1640 53

For many years, Whipple's disease was considered a rare, mainly intestinal disease causing malabsorption. At present, however, it appears to be multivisceral mainly occuring in subjects with specific and subtle cell-mediated immunity defects. Until recently, diagnosis and follow-up of treatment efficacy depended on PAS positive macrophage inclusions in duodenal biopsies. New diagnostic methods based on PCR gene amplification and immunohistochemistry are now available by DNA sequencing and culture, respectively, of the causal bacteria, which was recently renamed Tropheryma whipplei. Although results are still empirical, and the first randomized study is in progress, an evolution in the choice and duration of antibiotic treatment of this normally fatal disease has led to a marked reduction in clinical relapses, especially for neurological manifestations. The present review shows how recent medical advances have completely transformed the understanding of a disease first described a century ago.
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PMID:[Whipple's disease]. 1792 77

The neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) family of hormones exhibit a wide variety of biological actions on the mammalian gastrointestinal tract through known G-protein coupled receptor pathways. At least four receptor subtypes, denoted as Y(1), Y(2), Y(4) an Y(5), each with specific affinities to NPY ligands, serve as regulators of mucosal function, gastrointestinal motility and secretion. Investigations to date, however, have implicated the NPY peptides as mediators in the pathogenesis of numerous gastrointestinal disorders, including malabsorption, short gut, inflammatory bowel diseases, and forms of pancreatitis. Our understanding of these diseases and the interactions of NPY peptides have been advanced by the development of receptor agonists and antagonists that can be used experimentally in animal models. Potent selective PYY agonists have been developed that exhibit clinical potential as proabsorptive agents. NPY receptor agonists and antagonists as well as mice harboring null mutations in the Y(1) and Y(4) receptors have provided novel approaches in preventing intestinal inflammation and diarrhea. The use of competitive antagonists and Y(2) receptor knockouts have also aided in understanding secretory tone and electrogenic ion transport in the colon. In the pancreas, PYY suppresses amylase and cytokine release, which would be desirable in the clinical therapy of pancreatitis. Protein/DNA array analysis has revealed that PYY reduces transcription factor binding activity and disrupts signal transduction pathways activated by TNF-alpha in acinar cells. The present review gives an overview of NPY research in gastrointestinal disease and discusses its clinical relevance and potential use as therapy.
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PMID:NPY family of hormones: clinical relevance and potential use in gastrointestinal disease. 1797 80

Avian reovirus (ARV) causes several disease syndromes in poultry including arthritis, malabsorption syndrome and chronic respiratory disease that result in major economic losses. Early detection is very important for the control of the ARV-induced infections. This study was therefore aimed at developing a reliable assay protocol for identification of diseases (RAPID)-bioactive amplification with probing (BAP) assay for detection of ARV. This assay combines nested polymerase chain reaction (PCR) and magnetic bead-based DNA probing systems greatly increasing its sensitivity and specificity. Alignment of ARV S2 gene from different ARV genotypes and serotypes was done to find the highly conserved regions for primer and probe design. Two reverse transcription (RT)-PCR primer pairs, six nested PCR primer pairs, and one magnetic probe were tested to find the most specific ones for ARV detection. The optimal conditions for RT-PCR, nested PCR, and hybridization of magnetic probe were established. The optimal annealing temperatures for RT-PCR and nested PCR were 62.1 and 54.8 degrees C, respectively. The optimal hybridization temperature was 51.2 degrees C using hybridization buffer (5x SSC and 0.5% SDS). The sensitivity of the kit was 5 copies/microl of ARV genomic RNA. The kit was very specific as all negative controls failed to show any positive reactions. The kit shows good reproducibility with intra- and inter-assay coefficient of variation (CV) of 1.3 and 1.7%, respectively. In addition, different serotypes and genotypes of ARV were tested by RAPID-BAP assay to estimate the practicability of the kit in clinical samples. All of ARV serotypes and genotypes tested could be detected by this kit proving that the kit is suitable for clinical application.
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PMID:Development of a reliable assay protocol for identification of diseases (RAPID)-bioactive amplification with probing for detection of avian reovirus. 1831 46

Laser capture microdissection (LCM) is an efficient and precise method for obtaining pure cell populations or specific cells of interest from a given tissue sample. LCM has been applied to animal and human gastroenterology research in analyzing the protein, DNA, and RNA from all organs of the gastrointestinal system. There are numerous potential applications for this technology in gastroenterology research, including malignancies of the esophagus, stomach, colon, biliary tract, and liver. This technology can also be used to study gastrointestinal infections, inflammatory bowel disease, pancreatitis, motility, malabsorption, and radiation enteropathy. LCM has multiple advantages when compared with conventional methods of microdissection, and this technology can be exploited to identify precursors to disease, diagnostic biomarkers, and therapeutic interventions.
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PMID:Defining disease with laser precision: laser capture microdissection in gastroenterology. 1861 46

Whipple's disease of the brain is one of the most challenging neurological diagnoses. "Is it Whipple's disease?" is a frequent question, but rarely is the answer yes. The neurological manifestations do not help to distinguish primary from secondary Whipple's disease of the brain, and although MR brain scanning with gadolinium is mandatory, it can be normal and any abnormalities are non-specific. There must be a comprehensive search for multisystem involvement such as raised inflammatory markers, lymphadenopathy or malabsorption; biopsy of lymph node or duodenum may be necessary. PCR and DNA sequencing for Tropheryma whipplei on lymphocytes from blood and cerebrospinal fluid is essential. Treatment is as difficult as the diagnosis-there are no randomised controlled trials.
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PMID:Diagnosis and management of Whipple's disease of the brain. 1879 86

Treatment of systemic infections due to mycobacteria and HIV infection can lead to paradoxical worsening, the immune reconstitution inflammatory syndrome, in a minority of patients. Herein we describe a patient with Whipple's disease, a chronic systemic inflammatory disease caused by Tropheryma whipplei, who developed cutaneous and later ocular disease after initiation of antibiotic therapy. A 42-year-old man with a 12-year history of arthralgias presented with deteriorating health, including weight loss, diarrhea, fever, and acral hyperkeratosis. Whipple's disease was suspected and subsequently confirmed by finding periodic acid-Schiff (PAS)-positive foamy macrophages and T whipplei DNA by polymerase chain reaction (PCR) assays in duodenal biopsy specimens. After 5 weeks of antibiotic treatment with ceftriaxone, erythema nodosum (EN)-like lesions developed on the legs and trunk. Notably, lesional and nonlesional skin harbored intracellular and extracellular degenerated bacteria that were associated with a neutrophilic and granulomatous inflammatory response in lesional skin. Continued antibiotic therapy was associated with recurring EN-like skin nodules, orbital swelling, and facial herpes simplex virus 1 infection. Corticosteroid therapy controlled the duration and severity of the EN-like nodules and orbital swelling. Apart from cutaneous hyperpigmentation, skin disease in Whipple's disease is infrequent and can be categorized as disorders due to malnutrition from malabsorption or so-called reversal reactions consisting of reactive erythemas, and neutrophilic and granulomatous responses to T whipplei, the latter of which can represent an immune reconstitution inflammatory reaction after initiation of antibiotic therapy. Finally, based on the presence of T whipplei in normal skin, skin biopsy may serve as another site for diagnostic testing in patients suspected of having Whipple's disease.
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PMID:Erythema nodosum-like lesions in treated Whipple's disease: signs of immune reconstitution inflammatory syndrome. 1915 Feb 71

The apical sodium-dependent bile acid transporter (SLC10A2) plays a key role in the reabsorption of luminal bile acids into the enterohepatic circulation. Rare variations in SLC10A2 have been reported to be associated with Crohn's disease, primary bile acid malabsorption and familial hypertriglyceridemia; however, variants associated with reduced SLC10A2 expression have not been reported to date. In this study, we have performed a sequence analysis of SLC10A2 using genomic DNA of 93 individuals. A new haplotype structure was identified including ten variants with complete linkage disequilibrium (LD' = 1.0, r (2) = 1.0) of which six polymorphisms were novel. The sequence variants were confirmed in three independent cohorts (n = 1,290) by a recently established MALDI-TOF MS iPLEX assay. Remarkably, haplotype carriers with the minor allele exhibited significant reduced ileal SLC10A2 expression on mRNA levels (2.6-fold, P = 0.0009) and protein levels (2.4-fold, P = 0.0157). In future studies a single tag SNP selected of this haplotype block will provide reliable genetic testing to investigate systemically the influence of the SLC10A2 haplotype for disease susceptibility and/or drug response.
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PMID:Mutation screening of apical sodium-dependent bile acid transporter (SLC10A2): novel haplotype block including six newly identified variants linked to reduced expression. 1918 8

Folates are members of the B-class of vitamins, which are required for the synthesis of purines and pyrimidines, and for the methylation of essential biological substances, including phospholipids, DNA, and neurotransmitters. Folates cannot be synthesized de novo by mammals; hence, an efficient intestinal absorption process is required. Intestinal folate transport is carrier-mediated, pH-dependent and electroneutral, with similar affinity for oxidized and reduced folic acid derivatives. The various transporters, i.e. reduced folate carrier, proton-coupled folate transporter, folate-binding protein, and organic anion transporters, are involved in the folate transport process in various tissues. Any impairment in uptake of folate can lead to a state of folate deficiency, the most prevalent vitamin deficiency in world, affecting 10% of the population in the USA. Such impairments in folate transport occur in a variety of conditions, including chronic use of ethanol, some inborn hereditary disorders, and certain diseases. Among these, ethanol ingestion has been the major contributor to folate deficiency. Ethanol-associated folate deficiency can develop because of dietary inadequacy, intestinal malabsorption, altered hepatobiliary metabolism, enhanced colonic metabolism, and increased renal excretion. Ethanol reduces the intestinal and renal uptake of folate by altering the binding and transport kinetics of folate transport systems. Also, ethanol reduces the expression of folate transporters in both intestine and kidney, and this might be a contributing factor for folate malabsorption, leading to folate deficiency. The maintenance of intracellular folate homeostasis is essential for the one-carbon transfer reactions necessary for DNA synthesis and biological methylation reactions. DNA methylation is an important epigenetic determinant in gene expression, in the maintenance of DNA integrity and stability, in chromosomal modifications, and in the development of mutations. Ethanol, a toxin that is consumed regularly, has been found to affect the methylation of DNA. In addition to its effect on DNA methylation due to folate deficiency, ethanol could directly exert its effect through its interaction with one-carbon metabolism, impairment of methyl group synthesis, and affecting the enzymes regulating the synthesis of S-adenosylmethionine, the primary methyl group donor for most biological methylation reactions. Thus, ethanol plays an important role in the pathogenesis of several diseases through its potential ability to modulate the methylation of biological molecules. This review discusses the underlying mechanism of folate malabsorption in alcoholism, the mechanism of methylation-associated silencing of genes, and how the interaction between ethanol and folate deficiency affects the methylation of genes, thereby modulating epigenome stability and the risk of cancer.
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PMID:New perspectives on folate transport in relation to alcoholism-induced folate malabsorption--association with epigenome stability and cancer development. 1929 60

Familial hypercholesterolaemia (FH) is a common genetic disorder characterized by high plasma low-density lipoprotein (LDL)-cholesterol and premature coronary artery disease. Many factors, such as illness, high-dose statin therapy or a strict vegan diet can cause hypobetalipoproteinaemia (HBL). The more common secondary causes of HBL in the hospital setting include cachexia, intestinal malabsorption, malnutrition, severe liver disease and hyperthyroidism. We report a case of HBL in a 43-year-old man with previously demonstrated marked hypercholesterolaemia who attended a lipid disorders clinic for FH cascade screening. Surprisingly, a lipid profile taken at that time showed low plasma LDL-cholesterol and apolipoprotein B concentrations of 1.6 mmol/L and 0.61 g/L, respectively. He was not on lipid-lowering therapy. DNA sequencing showed that he was heterozygous for the LDLR gene mutation (C677R) present in other affected family members. Of interest, his serum transaminases were increased by approximately 3-fold and hepatitis serology and genotyping confirmed a diagnosis of hepatitis C virus (HCV) infection. In summary, we describe a case of HBL secondary to chronic HCV infection in a patient with FH, confirmed by mutational analysis.
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PMID:Hypobetalipoproteinaemia secondary to chronic hepatitis C virus infection in a patient with familial hypercholesterolaemia. 1948 12


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