Diagnostic utility of adipophilin immunostain in periocular carcinomas.
Milman T1, Schear MJ2, Eagle RC Jr3.Author information 1The New York Eye and Ear Infirmary, New York, New York. Electronic address: tmilman@nyee.edu.2New York Institute of Technology College of Osteopathic Medicine, New York, New York.3Wills Eye Hospital, Philadelphia, Pennsylvania.AbstractPURPOSE: To determine the efficacy of adipophilin immunohistochemistry in the diagnosis of sebaceous carcinoma of the ocular adnexal region and to provide the guidelines for interpretation of this immunostain.
Ophthalmology.Ophthalmology.2014 Apr;121(4):964-71. doi: 10.1016/j.ophtha.2013.10.041. Epub 2013 Nov 28.
PURPOSE: To determine the efficacy of adipophilin immunohistochemistry in the diagnosis of sebaceous carcinoma of the ocular adnexal region and to provide the guidelines for interpretation of this immunostain.DESIGN: Retrospective, histopathologic case series.PARTICIPANTS: A total of 25 patients wit
Model steatogenic compounds (amiodarone, valproic acid, and tetracycline) alter lipid metabolism by different mechanisms in mouse liver slices.
Szalowska E1, van der Burg B2, Man HY2, Hendriksen PJ1, Peijnenburg AA1.Author information 1Cluster of Bioassays and Toxicology, RIKILT - Institute of Food Safety, Wageningen University and Research Centre, Wageningen, The Netherlands.2BDS BioDetection Systems, Amsterdam, The Netherlands.AbstractAlthough drug induced steatosis represents a mild type of hepatotoxicity it can progress into more severe non-alcoholic steatohepatitis. Current models used for safety assessment in drug development and chemical risk assessment do not accurately predict steatosis in humans. Therefore, new models need to be developed to screen compounds for steatogenic properties. We have studied the usefulness of mouse precision-cut liver slices (PCLS) as an alternative to animal testing to gain more insight into the mechanisms involved in the steatogenesis. To this end, PCLS were incubated 24 h with the model steatogenic compounds: amiodarone (AMI), valproic acid (VA), and tetracycline (TET). Transcriptome analysis using DNA microarrays was used to identify genes and processes affected by these compounds. AMI and VA upregulated lipid metabolism, whereas processes associated with extracellular matrix remodelling and inflammation were downregulated. TET downregulated mitochondrial functions, lipid metabolism, and fibrosis. Furthermore, on the basis of the transcriptomics data it was hypothesized that all three compounds affect peroxisome proliferator activated-receptor (PPAR) signaling. Application of PPAR reporter assays classified AMI and VA as PPARγ and triple PPARα/(β/δ)/γ agonist, respectively, whereas TET had no effect on any of the PPARs. Some of the differentially expressed genes were considered as potential candidate biomarkers to identify PPAR agonists (i.e. AMI and VA) or compounds impairing mitochondrial functions (i.e. TET). Finally, comparison of our findings with publicly available transcriptomics data showed that a number of processes altered in the mouse PCLS was also affected in mouse livers and human primary hepatocytes exposed to known PPAR agonists. Thus mouse PCLS are a valuable model to identify early mechanisms of action of compounds altering lipid metabolism.
PloS one.PLoS One.2014 Jan 29;9(1):e86795. doi: 10.1371/journal.pone.0086795. eCollection 2014.
Although drug induced steatosis represents a mild type of hepatotoxicity it can progress into more severe non-alcoholic steatohepatitis. Current models used for safety assessment in drug development and chemical risk assessment do not accurately predict steatosis in humans. Therefore, new models nee
Nonalcoholic fatty liver disease is associated with lower hepatic and erythrocyte ratios of phosphatidylcholine to phosphatidylethanolamine.
Arendt BM1, Ma DW, Simons B, Noureldin SA, Therapondos G, Guindi M, Sherman M, Allard JP.Author information 1a Department of Medicine, University Health Network, Toronto, ON M5G 2C4, Canada.AbstractNonalcoholic fatty liver disease (NAFLD) is associated with altered hepatic lipid composition. Animal studies suggest that the hepatic ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) contributes to steatogenesis and inflammation. This ratio may be influenced by dysregulation of the PE N-methyltransferase (PEMT) pathway or by a low-choline diet. Alterations in the liver may also influence lipid composition in circulation such as in erythrocytes, which therefore may have utility as a biomarker of hepatic disease. Currently, no study has assessed both liver and erythrocyte PC/PE ratios in NAFLD. The aim of this study was to compare the PC/PE ratio in the liver and erythrocytes of patients with simple steatosis (SS) or nonalcoholic steatohepatitis (NASH) with that of healthy controls. PC and PE were measured by mass spectrometry in 28 patients with biopsy-proven NAFLD (14 SS, 14 NASH) and 9 healthy living liver donors as controls. The hepatic PC/PE ratio was lower in SS patients (median [range]) (1.23 [0.27-3.40]) and NASH patients (1.29 [0.77-3.22]) compared with controls (3.14 [2.20-3.73]); both p < 0.001) but it was not different between SS and NASH. PC was lower and PE higher in the liver of SS patients compared with controls, whereas in NASH patients only PE was higher. The PC/PE ratio in erythrocytes was also lower in SS and NASH patients compared with controls because of lower PC in both patient groups. PE in erythrocytes was not different among the groups. In conclusion, NAFLD patients have a lower PC/PE ratio in the liver and erythrocytes than do healthy controls, which may play a role in the pathogenesis. The underlying mechanisms require further investigation.
Applied physiology, nutrition, and metabolism = Physiologie appliquée, nutrition et métabolisme.Appl Physiol Nutr Metab.2013 Mar;38(3):334-40. doi: 10.1139/apnm-2012-0261. Epub 2012 Oct 15.
Nonalcoholic fatty liver disease (NAFLD) is associated with altered hepatic lipid composition. Animal studies suggest that the hepatic ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) contributes to steatogenesis and inflammation. This ratio may be influenced by dysregulation of th
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