Medicine and Health Sciences Commons^™

Molecular Processes That Handle — And Mishandle — Dietary Lipids, Kevin Jon Williams

Department of Medicine Faculty Papers

Overconsumption of lipid-rich diets, in conjunction with physical inactivity, disables and kills staggering numbers of people worldwide. Recent advances in our molecular understanding of cholesterol and triglyceride transport from the small intestine to the rest of the body provide a detailed picture of the fed/fasted and active/sedentary states. Key surprises include the unexpected nature of many pivotal molecular mediators, as well as their dysregulation — but possible reversibility — in obesity, diabetes, inactivity, and related conditions. These mechanistic insights provide new opportunities to correct dyslipoproteinemia, accelerated atherosclerosis, insulin resistance, and other deadly sequelae of overnutrition and underexertion.

Molecular And Macromolecular Alterations Of Recombinant Adenoviral Vectors Do Not Resolve Changes In Hepatic Drug Metabolism During Infection., Shellie M Callahan, Piyanuch Wonganan, Maria A Croyle

Student and Faculty Publications

In this report we test the hypothesis that long-term virus-induced alterations in CYP occur from changes initiated by the virus that may not be related to the immune response. Enzyme activity, protein expression and mRNA of CYP3A2, a correlate of human CYP3A4, and CYP2C11, responsive to inflammatory mediators, were assessed 0.25, 1, 4, and 14 days after administration of several different recombinant adenoviruses at a dose of 5.7 x 1012 virus particles (vp)/kg to male Sprague Dawley rats. Wild type adenovirus, containing all viral genes, suppressed CYP3A2 and 2C11 activity by 37% and 39%, respectively within six hours. Levels fell …

Blood Utilization In Children Managed Non-Operatively For Blunt Solid Organ Injury., Scott J. Keckler, Kuojen Tsao, Susan W. Sharp, G W. Holcomb Iii, Daniel J. Ostlie, Shawn D. St Peter

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Blood product utilization is an important issue in health care, given the frequent shortages in hospitals and the societal burden required to maintain the supply. Therefore, we retrospectively audited our blunt spleen/liver trauma experience to determine the percentage of cross-matched blood that was transfused to see whether more stringent typing criteria should be applied.

METHODS: A retrospective analysis of a recent 7-year experience with nonoperative management in patients with blunt spleen or liver injury was performed. Demographics, packed red blood cells prepared by cross-match, and transfusions were measured. Unmatched, O-type blood given in the trauma bay was excluded. Patients …

Trail Mediates Liver Injury By The Innate Immune System In The Bile Duct-Ligated Mouse., Alisan Kahraman, Fernando J. Barreyro, Steven F. Bronk, Nathan W. Werneburg, Justin L. Mott, Yuko Akazawa, Howard C Masuoka, Charles L Howe, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

The contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a death ligand expressed by cells of the innate immune system, to cholestatic liver injury has not been explored. Our aim was to ascertain if TRAIL contributes to liver injury in the bile duct-ligated (BDL) mouse. C57/BL6 wild-type (wt), TRAIL heterozygote (TRAIL(+/-)), and TRAIL knockout (TRAIL(-/-)) mice were used for these studies. Liver injury and fibrosis were examined 7 and 14 days after BDL, respectively. Hepatic TRAIL messenger RNA (mRNA) was 6-fold greater in BDL animals versus sham-operated wt animals (P < 0.01). The increased hepatic TRAIL expression was accompanied by an increase in liver accumulation of natural killer 1.1 (NK 1.1)-positive NK and natural killer T (NKT) cells, the predominant cell types expressing TRAIL. Depletion of NK 1.1-positive cells reduced hepatic TRAIL mRNA expression and serum alanine aminotransferase (ALT) values. Consistent with a role for NK/NKT cells in this model of liver injury, stress ligands necessary for their recognition of target cells were also up-regulated in hepatocytes following BDL. Compared to sham-operated wt mice, BDL mice displayed a 13-fold increase in terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and an 11-fold increase in caspase 3/7-positive hepatocytes (P < 0.01). The number of TUNEL and caspase 3/7-positive cells was reduced by >80% in BDL TRAIL knockout animals (P < 0.05). Likewise, liver histology, number of bile infarcts, serum ALT values, hepatic fibrosis, and animal survival were also improved in BDL TRAIL(-/-) animals as compared to wt animals. Conclusion: These observations support a pivotal role for TRAIL in cholestatic liver injury mediated by NK 1.1-positive NK/NKT cells.

Chronic Late-Gestation Hypoglycemia Upregulates Hepatic Pepck Associated With Increased Pgc1alpha Mrna And Phosphorylated Creb In Fetal Sheep., Paul J Rozance, Sean W Limesand, James S Barry, Laura D Brown, Stephanie R Thorn, Dan Loturco, Timothy Regnault, Jacob E Friedman, William W Hay

Paediatrics Publications

Hepatic glucose production is normally activated at birth but has been observed in response to experimental hypoglycemia in fetal sheep. The cellular basis for this process remains unknown. We determined the impact of 2 wk of fetal hypoglycemia during late gestation on enzymes responsible for hepatic gluconeogenesis, focusing on the insulin-signaling pathway, transcription factors, and coactivators that regulate gluconeogenesis. Hepatic phosphoenolpyruvate carboxykinase and glucose-6-phosphatase mRNA increased 12-fold and 7-fold, respectively, following chronic hypoglycemia with no change in hepatic glycogen. Chronic hypoglycemia decreased fetal plasma insulin with no change in glucagon but increased plasma cortisol 3.5-fold. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha mRNA …

Seasonal Variation Of Vitamin A And Beta-Carotene Levels In Ghezel Sheep, Gholamreza Afshari, A. Hasanpour, H. Haghpanah, Bahram Amoughli-Tabrizi

Turkish Journal of Veterinary & Animal Sciences

The present study was conducted to investigate the variations in blood serum and hepatic levels of vitamin A and b-carotene in Ghezel sheep throughout the year. From 1000 sheep aged 1-5 years, blood and liver samples were collected before and after slaughter. The levels of vitamin A and \beta-carotene in both samples were determined spectrophotometrically. The results showed significant differences between summer and winter values (P < 0.05), but no differences were found between the sexes (P > 0.05). There were significant correlations between the vitamin A levels in serum and the liver (P < 0.05). Due to low levels of vitamin A and \beta -carotene in Ghezel sheep during the winter, supplementary feeding of vitamin A is recommended during this season.

Co-Existence Of Intrahepatic Bile Duct Adenoma And Colonic Adenocarcinoma, Gülen Akyol, Nüket Üzüm, Nusret Akyürek, Bülent Menteş

Turkish Journal of Medical Sciences

Intrahepatic bile duct adenoma (BDA) is a rare benign tumor of the liver that is usually diagnosed by microscopic examination. Most cases are incidentally discovered during surgery or autopsy. Here, we report the co-existence of colonic adenocarcinoma and intrahepatic BDA mimicking metastasis in a 62-year-old man. The patient underwent metastasectomy because of the presence of colonic adenocarcinoma diagnosed at almost the same time. The diagnosis was benign in frozen sections intraoperatively and total colectomy was performed during the same operation. BDA should be included in the diseases to be differentiated from hepatic primary or metastatic tumors.

Ultrasonographic Examination Of The Goat Liver, Sarang Soroori, Afshin Raoofi, Ali Reza Vajhi, Sara Ghorbani Nezami

Turkish Journal of Veterinary & Animal Sciences

The purpose of this study was to obtain detailed information about the normal size and texture of the goat liver by means of ultrasonographic examination. The structure, location, and size of the liver, portal vein, and caudal vena cava were examined ultrasonographically in 6 goats. The angle of the liver and the thickness of the gallbladder wall were also determined. Examinations were performed on the right side of the abdomen, from the 6th through 12th intercostal space, using a 6-13 MHz linear transducer. In each intercostal space the dimensions of the liver, and if visible, the location and diameter of …

Temporal And Functional Profile Of The Transcriptional Regulatory Network In The Early Regenerative Response To Partial Hepatectomy In The Rat., Egle Juskeviciute, Rajanikanth Vadigepalli, Jan B Hoek

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: The goal of these studies was to characterize the transcriptional network regulating changes in gene expression in the remnant liver of the rat after 70% partial hepatectomy (PHx) during the early phase response including the transition of hepatocytes from the quiescent (G0) state and the onset of the G1 phase of the cell cycle. RESULTS: The transcriptome of remnant livers was monitored at 1, 2, 4, and 6 hours after PHx using cDNA microarrays. Differentially regulated genes were grouped into six clusters according their temporal expression profiles. Promoter regions of genes in these clusters were examined for shared transcription …