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Find video protocols related to scientific articles indexed in Pubmed.
Clinical, histopathological and immunohistochemical characterization of a novel equine ocular disorder: heterochromic iridocyclitis with secondary keratitis in adult horses.
Vet Ophthalmol
PUBLISHED: 11-18-2014
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To describe the clinical, histopathologic and immunohistochemical characteristics of an equine ocular inflammatory disease resulting in anterior uveitis and corneal endothelial inflammation associated with iris pigment dispersion and retrocorneal fibrous membrane (RFM) formation.
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Subsurface Chlorophyll Maximum Layers: Enduring Enigma or Mystery Solved?
Ann Rev Mar Sci
PUBLISHED: 09-25-2014
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The phenomenon of subsurface chlorophyll maximum layers (SCMLs) is not a unique ecological response to environmental conditions; rather, a broad range of interacting processes can contribute to the formation of persistent layers of elevated chlorophyll a concentration (Chl) that are nearly ubiquitous in stratified surface waters. Mechanisms that contribute to the formation and maintenance of the SCMLs include a local maximum in phytoplankton growth rate near the nutricline, photoacclimation of pigment content that leads to elevated Chl relative to phytoplankton biomass at depth, and a range of physiologically influenced swimming behaviors in motile phytoplankton and buoyancy control in diatoms and cyanobacteria that can lead to aggregations of phytoplankton in layers, subject to grazing and physical control. A postulated typical stable water structure characterizes consistent patterns in vertical profiles of Chl, phytoplankton biomass, nutrients, and light across a trophic gradient structured by the vertical flux of nutrients and characterized by the average daily irradiance at the nutricline. Hypothetical predictions can be tested using a nascent biogeochemical global ocean observing system. Partial results to date are generally consistent with predictions based on current knowledge, which has strong roots in research from the twentieth century. Expected final online publication date for the Annual Review of Marine Science Volume 7 is January 03, 2015. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
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Lack of association of ABCB4 insertion mutation with gallbladder mucoceles in dogs.
J. Vet. Diagn. Invest.
PUBLISHED: 04-23-2014
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The etiology of canine gallbladder mucocele (GBM) has not yet been identified. However, several studies have linked GBM in dogs to particular breeds (Shetland Sheepdogs are commonly implicated), concurrent endocrine disease (hyperadrenocorticism and/or hypothyroidism), and a mutation in the canine ABCB4 gene (ABCB4 1583_1584G), particularly in Shetland Sheepdogs. The current study assessed ABCB4 1583_1584G, in a wider sample of dogs with GBM compared with age and breed-matched controls. ABCB4 1583_1584G was identified in 4 of 8 Shetland Sheepdogs and 13 of 28 other breeds with GBM. ABCB4 1583_1584G was also detected in 9 of 12 Shetland Sheepdogs and 23 of 37 other breeds that did not have GBM. No statistically significant association existed between ABCB4 1583_1584G and the presence of GBM for all dogs combined or for Shetland Sheepdogs alone. In contrast to previously reported findings, the current study did not identify a strong association between ABCB4 1583_1584G and GBM in Shetland Sheepdogs or other breeds.
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Visualizing surface area and volume of lumens in three dimensions using images from histological sections.
J Microsc
PUBLISHED: 03-18-2014
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Visualizing the interior (lumen) of a tubular structure within tissue can provide a unique perspective on anatomical organization of the tissue. Portal tracts of the liver contain several vessels and ducts in various patterns of intertwining branches and are an example of such spaces. An inexpensive method, using light microscopy and a sample of conventionally stained canine livers, was used to colorize and allow visualization of the lumens of vessels within the portal tract in three dimensions. When the colour of the background was digitally cleared and the lumen filled with a solid colour, it was possible to measure areas and volumes of the portal vein, arteries, bile ducts and lymphatics. Significant differences between vessels and ducts across lobes and gender in control samples are discussed. Differences were also found between control and mixed breed dogs and between controls and a dog that died of accidental traumatic haemorrhage. These differences are discussed in relation to visualizing lumens using images generated from a light microscope. Vessels in plants such as xylem and continuously formed spaces resulting from ice formation are other examples where this technique could be applied.
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Liver biomarker and in vitro assessment confirm the hepatic origin of aminotransferase elevations lacking histopathological correlate in beagle dogs treated with GABAA receptor antagonist NP260.
Toxicol. Appl. Pharmacol.
PUBLISHED: 03-14-2014
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NP260 was designed as a first-in-class selective antagonist of ?4-subtype GABAA receptors that had promising efficacy in animal models of pain, epilepsy, psychosis, and anxiety. However, development of NP260 was complicated following a 28-day safety study in dogs in which pronounced elevations of serum aminotransferase levels were observed, although there was no accompanying histopathological indication of hepatocellular injury. To further investigate the liver effects of NP260, we assayed stored serum samples from the 28-day dog study for liver specific miRNA (miR-122) as well as enzymatic biomarkers glutamate dehydrogenase and sorbitol dehydrogenase, which indicate liver necrosis. Cytotoxicity assessments were conducted in hepatocytes derived from dog, rat, and human liver samples to address the species specificity of the liver response to NP260. All biomarkers, except ALT, returned toward baseline by Day 29 despite continued drug treatment, suggesting adaptation to the initial injury. In vitro analysis of the toxicity potential of NP260 to primary hepatocytes indicated a relative sensitivity of dog>human>rat, which may explain, in part, why the liver effects were not evident in the rodent safety studies. Taken together, the data indicate that a diagnostic biomarker approach, coupled with sensitive in vitro screening strategies, may facilitate interpretation of toxicity potential when an adaptive event masks the underlying toxicity.
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Does speed matter? Revision rates and functional outcomes in TKA in relation to duration of surgery.
J Arthroplasty
PUBLISHED: 03-05-2014
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Longer operative times may be required in complex total knee arthroplasty (TKA), however little is known about outcomes in procedures performed rapidly. We analysed 58,009 primary TKAs from the New Zealand National Joint Registry. The mean surgical duration was 89 minutes, and 50% of procedures lasted between 60 and 89 minutes. There was no difference in adjusted revision rates for groups lasting between 40 and 120 minutes, however procedures lasting >120 minutes had significantly higher revision rates. There was a higher revision rate in TKAs lasting <40 minutes (0.71 vs 0.48 revisions per 100 component years) but this was not statistically significant (P = 0.1). For primary TKAs lasting less than 120 minutes, further shortening operative time did not improve outcome, and very rapid procedures (<40 minutes) may lead to an increased risk of revision.
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Differential expression of Hedgehog/Notch and transforming growth factor-? in human abdominal aortic aneurysms.
J. Vasc. Surg.
PUBLISHED: 02-23-2014
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The molecular mechanisms leading to the development of abdominal aortic aneurysms (AAAs) remain poorly understood. The aim of this study was to determine the expression of Sonic Hedgehog (SHh), transforming growth factor ? (TGF-?), and Notch signaling components in human aneurysmal and nonaneurysmal aorta in vivo.
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Role of human pregnane X receptor in high fat diet-induced obesity in pre-menopausal female mice.
Biochem. Pharmacol.
PUBLISHED: 02-15-2014
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Obesity is a complex metabolic disorder that is more prevalent among women. Until now, the only relevant rodent models of diet-induced obesity were via the use of ovariectomized ("postmenopausal") females. However, recent reports suggest that the xenobiotic nuclear receptor pregnane X receptor (PXR) may contribute to obesity. Therefore, we compared the roles of mouse and human PXRs in diet-induced obesity between wild type (WT) and PXR-humanized (hPXR) transgenic female mice fed either control or high-fat diets (HFD) for 16 weeks. HFD-fed hPXR mice gained weight more rapidly than controls, exhibited hyperinsulinemia, and impaired glucose tolerance. Fundamental differences were observed between control-fed hPXR and WT females: hPXR mice possessed reduced estrogen receptor ? (ER?) but enhanced uncoupling protein 1 (UCP1) protein expression in white adipose tissue (WAT); increased protein expression of the hepatic cytochrome P450 3A11 (CYP3A11) and key gluconeogenic enzymes phosphoenolpyruvate carboxykinase and glucose 6-phosphatase, and increased total cholesterol. Interestingly, HFD ingestion induced both UCP1 and glucokinase protein expression in WT mice, but inhibited these enzymes in hPXR females. Unlike WT mice, CYP3A11 protein, serum 17?-estradiol levels, and WAT ER? expression were unaffected by HFD in hPXR females. Together, these studies indicate that the hPXR gene promotes obesity and metabolic syndrome by dysregulating lipid and glucose homeostasis while inhibiting UCP1 expression. Furthermore, our studies indicate that the human PXR suppresses the protective role of estrogen in metabolic disorders. Finally, these data identify PXR-humanized mice as a promising in vivo research model for studying obesity and diabetes in women.
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Surveillance after initial surgery for pediatric and adolescent girls with stage I ovarian germ cell tumors: report from the Children's Oncology Group.
J. Clin. Oncol.
PUBLISHED: 01-06-2014
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To determine whether overall survival (OS) can be preserved for patients with stage I pediatric malignant ovarian germ cell tumor (MOGCT) with an initial strategy of surveillance after surgical resection.
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Role of pregnane X receptor in obesity and glucose homeostasis in male mice.
J. Biol. Chem.
PUBLISHED: 12-20-2013
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Clinical obesity is a complex metabolic disorder affecting 1 in 3 adults. Recent reports suggest that pregnane X receptor (PXR), a xenobiotic nuclear receptor important for defense against toxic agents and for eliminating drugs and other xenobiotics, may be involved in obesity. Noting differences in ligand specificities between human and mouse PXRs, the role of PXR in high-fat diet (HFD)-induced obesity was examined using male PXR-humanized (hPXR) transgenic and PXR-knockout (PXR-KO) mice in comparison to wild-type (WT) mice. After 16 weeks on either a control diet or HFD, WT mice showed greater weight gain, while PXR-KO mice gained less weight due to their resistance to HFD-induced decreases in adipose tissue peroxisome proliferator-activated receptor ? and induction of hepatic carnitine palmitoyltransferase 1, suggesting increased energy metabolism. Interestingly, control-fed PXR-KO mice exhibited hepatomegaly, hyperinsulinemia and hyperleptinemia, but hypoadiponectinemia and lower adiponectin receptor R2 mRNA levels relative to WT mice. Evaluation of these biologic indicators in hPXR mice fed a control diet or HFD revealed further differences between the mouse and human receptors. Importantly, while HFD-fed hPXR mice were resistant to HFD-induced obesity, both PXR-KO and hPXR mice exhibited impaired induction of glucokinase involved in glucose utilization and displayed elevated fasting glucose levels and severely impaired glucose tolerance. Moreover, the basal hepatic levels of the gluconeogenic enzyme phosphoenoylpyruvate carboxykinase 1 were increased in hPXR mice, compared with WT mice. Altogether, while the mouse PXR promotes HFD-induced obesity, the hPXR mouse carries a genetic predisposition for type 2 diabetes and thus provides a model for exploring the role of human PXR in the metabolic syndrome.
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Gene expression analysis and urinary biomarker assays reveal activation of tubulointerstitial injury pathways in a rodent model of chronic proteinuria (Doxorubicin nephropathy).
Nephron Exp. Nephrol.
PUBLISHED: 09-08-2013
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Background: Tubular atrophy and interstitial fibrosis are well-recognized sequelae of chronic proteinuria; however, little is known regarding the molecular pathways activated within tubulointerstitium in chronic proteinuric nephropathies. Methods: To investigate the molecular mechanisms of proteinuria-associated tubulointerstitial (TI) disease, doxorubicin nephropathy was induced in rats. Progression of disease was monitored with weekly urinary biomarker assays. Because histopathology revealed multifocal TI injury, immunodirected laser capture microdissection was used to identify and isolate injured proximal tubules, as indicated by kidney injury molecule-1 immunolabeling. Adjacent interstitial cells were harvested separately. Gene expression microarray, manual annotation of gene lists, and Gene Set Enrichment Analysis were performed. A subset of the regulated transcripts was validated by quantitative PCR and immunohistochemistry. Results: Severe proteinuria preceded tubular injury biomarkers by 1 week. Histology revealed multifocal, mild TI damage at 3 weeks, which progressed in severity at 5 weeks. Affymetrix microarray analysis revealed tissue-specific regulation of gene expression. Manual annotation of gene lists, gene set enrichment analysis, and urinary biomarker assays revealed similarities to pathways activated in direct TI injuries. This suggests commonalities amongst the molecular mechanisms of TI injury secondary to proteinuria, ischemia-reperfusion, and nephrotoxicity. © 2013 S. Karger AG, Basel.
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Biliary Proliferative Lesions in the Sprague-Dawley Rat: Adverse/Non-adverse.
Toxicol Pathol
PUBLISHED: 08-19-2013
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Whether biliary proliferative lesions in nonclinical species are predictive of potential hepatotoxicity in humans depends, at least in part, on the nature and severity of such changes in the nonclinical species. We reviewed published literature (clinical and nonclinical) and experimental data from rat toxicology studies conducted by GlaxoSmithKline and the National Institute of Environmental Health Sciences National Toxicology Program in an effort to better characterize the relative risk of hepatobiliary effects in humans. Available evidence supports the interpretation that minimal "typical" appearing bile duct hyperplasia limited to the portal triads may be considered non-adverse in the rat and is of little to no concern to humans. The toxicological relevance of mild to moderate "typical" hyperplasia is less certain, and may be considered adverse in the rat and potentially pose a risk for humans, particularly if accompanied by evidence of hepatobiliary injury or functional compromise. In addition, any proliferative lesion that includes atypical or dysplastic epithelial changes, oval cell proliferation, and/or significant extension beyond the portal tracts is considered more ominous and may be considered adverse in the rat.
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Evaluation of fluorescence in situ hybridization for the detection of bacteria in feline inflammatory liver disease.
J. Feline Med. Surg.
PUBLISHED: 07-24-2013
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The etiopathogenesis of feline inflammatory liver disease (ILD) is unclear. Therefore, we sought to determine the presence and distribution of bacteria within the livers of cats with ILD using eubacterial fluorescence in situ hybridization (FISH). Histopathology from 39 cats with ILD and 19 with histologically normal livers (C) were classified using World Small Animal Veterinary Association guidelines. Hepatic sections were examined by 16 and 23S ribosomal RNA FISH. Antibodies against cytokeratins and factor VIIIa were used to distinguish bile ducts and vascular structures. Histopathologic findings included non-specific reactive hepatitis (12), neutrophilic cholangitis (NC; 12), lymphocytic cholangitis (seven), cholestasis/obstruction (three), probable lymphoma (three) and acute hepatitis (two). Bacteria were observed in 21/39 ILD and 3/19 C (P = 0.0054). In 8/39 ILD and 2/19 C bacteria were restricted to the outer liver capsule (P = 0.29) and may represent contaminants. The prevalence of intrahepatic bacteria was higher (P = 0.008) in ILD (13/31) than C (1/17). Bacteria in ILD were more frequently (P <0.0001) localized to portal vessels, venous sinusoids and parenchyma (12/13) than bile duct (1/13). Bacterial colonization was highest in Escherichia coli-positive NC cats. Concurrent non-hepatic disease, predominantly pancreatic and intestinal (8/10 cats biopsied), was present in all 13 cats with intrahepatic bacteria. Bacterial culture was positive (predominantly E coli and Enterococcus species) in 11/23 (48%) samples, and concurred with FISH in 15/23 cases. The presence of intrahepatic bacteria in 13/31 (41%) cats with ILD suggests a role in etiopathogenesis. The distribution of bacteria within the liver supports the possibility of colonization via either enteric translocation or hematogenous seeding.
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Dietary fructose induces endotoxemia and hepatic injury in calorically controlled primates.
Am. J. Clin. Nutr.
PUBLISHED: 06-21-2013
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Controversy exists regarding the causative role of dietary fructose in obesity and fatty liver diseases. Clinical trials have indicated that negative health consequences may occur only when fructose is consumed within excess calories. Animal studies have suggested that fructose impairs intestinal integrity and leads to hepatic steatosis (HS).
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Inhibition of patched-1 prevents injury-induced neointimal hyperplasia.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 06-13-2013
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To determine the role of patched receptor (Ptc)-1 in mediating pulsatile flow-induced changes in vascular smooth muscle cell growth and vascular remodeling.
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Impact of an electronic medication management system on hospital doctors and nurses work: a controlled pre-post, time and motion study.
J Am Med Inform Assoc
PUBLISHED: 05-28-2013
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To quantify and compare the time doctors and nurses spent on direct patient care, medication-related tasks, and interactions before and after electronic medication management system (eMMS) introduction.
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Necrolytic migratory erythema associated with a glucagon-producing primary hepatic neuroendocrine carcinoma in a cat.
Vet. Dermatol.
PUBLISHED: 04-17-2013
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In humans, necrolytic migratory erythema (NME) is a syndrome with a characteristic skin rash that is associated most often with a pancreatic glucagonoma and is recognized as part of the glucagonoma syndrome. In veterinary medicine, NME (also called as superficial necrolytic dermatitis, hepatocutaneous syndrome or metabolic epidermal necrosis) has been described in dogs in association with chronic liver diseases or, less frequently, glucagonoma, but NME associated with glucagonoma has not previously been reported in cats.
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Identification of a pegivirus (GB virus-like virus) that infects horses.
J. Virol.
PUBLISHED: 04-17-2013
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The recent identification of nonprimate hepaciviruses in dogs and then in horses prompted us to look for pegiviruses (GB virus-like viruses) in these species. Although none were detected in canines, we found widespread natural infection of horses by a novel pegivirus. Unique genomic features and phylogenetic analyses confirmed that the tentatively named equine pegivirus (EPgV) represents a novel species within the Pegivirus genus. We also determined that EPgV causes persistent viremia whereas its clinical significance is undetermined.
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Identification of rodent homologs of hepatitis C virus and pegiviruses.
MBio
PUBLISHED: 04-11-2013
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Hepatitis C virus (HCV) and human pegivirus (HPgV or GB virus C) are globally distributed and infect 2 to 5% of the human population. The lack of tractable-animal models for these viruses, in particular for HCV, has hampered the study of infection, transmission, virulence, immunity, and pathogenesis. To address this challenge, we searched for homologous viruses in small mammals, including wild rodents. Here we report the discovery of several new hepaciviruses (HCV-like viruses) and pegiviruses (GB virus-like viruses) that infect wild rodents. Complete genome sequences were acquired for a rodent hepacivirus (RHV) found in Peromyscus maniculatus and a rodent pegivirus (RPgV) found in Neotoma albigula. Unique genomic features and phylogenetic analyses confirmed that these RHV and RPgV variants represent several novel virus species in the Hepacivirus and Pegivirus genera within the family Flaviviridae. The genetic diversity of the rodent hepaciviruses exceeded that observed for hepaciviruses infecting either humans or non-primates, leading to new insights into the origin, evolution, and host range of hepaciviruses. The presence of genes, encoded proteins, and translation elements homologous to those found in human hepaciviruses and pegiviruses suggests the potential for the development of new animal systems with which to model HCV pathogenesis, vaccine design, and treatment.
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Chikungunya virus host range E2 transmembrane deletion mutants induce protective immunity against challenge in C57BL/6J mice.
J. Virol.
PUBLISHED: 04-03-2013
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A vaccine against Chikungunya virus (ChikV), a reemerging pathogenic arbovirus, has been made by attenuating wild-type (WT) virus via truncation of the transmembrane domain (TMD) of E2 and selecting for host range (HR) mutants. Mice are a standard model system for ChikV disease and display the same symptoms of the disease seen in humans. Groups of mice were inoculated with one of three ChikV HR mutants to determine the ability of each mutant strain to elicit neutralizing antibody and protective immunity upon virus challenge. One mutant, ChikV TM17-2, fulfilled the criteria for a good vaccine candidate. It displayed no reactogenicity at the site of injection, no tissue disease in the foot/ankle and quadriceps, and no evidence of viral persistence in foot/ankle tissues 21 days after infection. Upon challenge with a highly pathogenic strain of ChikV, the mutant blocked viral replication in all tissues tested. This study identified a ChikV HR mutant that grows to high levels in insect cells but was restricted in the ability to assemble virus in mammalian cells in vitro. The study demonstrates that these HR strains are attenuated in the mammalian host and warrant further development as live-attenuated vaccine strains.
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Robotic-assisted laparoscopic stage II restorative proctectomy for toxic ulcerative colitis.
Int J Med Robot
PUBLISHED: 09-16-2011
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There is a paucity of literature reporting minimally invasive proctectomy for ulcerative colitis (UC). We report a novel application of a robotic system to perform restorative proctectomy in patients with toxic UC.
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Differential effects of daily-moderate versus weekend-binge alcohol consumption on atherosclerotic plaque development in mice.
Atherosclerosis
PUBLISHED: 06-20-2011
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We examined the effect of daily-moderate (2 drinks/day, 7 days/week) and weekend-binge (7 drinks/day, 2 days/week) patterns of alcohol consumption on plasma lipid levels and physiological parameters of atherosclerotic plaque development.
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Development of an animal model for radiofrequency ablation of primary, virally induced hepatocellular carcinoma in the woodchuck.
J Vasc Interv Radiol
PUBLISHED: 05-27-2011
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To develop a consistent and reproducible method in an animal model for studies of radiofrequency (RF) ablation of primary hepatocellular carcinoma (HCC).
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Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior.
BMC Cancer
PUBLISHED: 05-26-2011
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Histiocytic malignancies in both humans and dogs are rare and poorly understood. While canine histiocytic sarcoma (HS) is uncommon in the general domestic dog population, there is a strikingly high incidence in a subset of breeds, suggesting heritable predisposition. Molecular cytogenetic profiling of canine HS in these breeds would serve to reveal recurrent DNA copy number aberrations (CNAs) that are breed and/or tumor associated, as well as defining those shared with human HS. This process would identify evolutionarily conserved cytogenetic changes to highlight regions of particular importance to HS biology.
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Glycogen synthase kinase 3 beta positively regulates Notch signaling in vascular smooth muscle cells: role in cell proliferation and survival.
Basic Res. Cardiol.
PUBLISHED: 04-29-2011
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The role of glycogen synthase kinase 3 beta (GSK-3?) in modulating Notch control of vascular smooth muscle cell (vSMC) growth (proliferation and apoptosis) was examined in vitro under varying conditions of cyclic strain and validated in vivo following changes in medial tension and stress. Modulation of GSK-3? in vSMC following ectopic expression of constitutively active GSK-3?, siRNA knockdown and pharmacological inhibition with SB-216763 demonstrated that GSK-3? positively regulates Notch intracellular domain expression, CBF-1/RBP-J? transactivation and downstream target gene mRNA levels, while concomitantly promoting vSMC proliferation and inhibiting apoptosis. In contrast, inhibition of GSK-3? attenuated Notch signaling and decreased vSMC proliferation and survival. Exposure of vSMC to cyclic strain environments in vitro using both a Flexercell™ Tension system and a novel Sylgard™ phantom vessel following bare metal stent implantation revealed that cyclic strain inhibits GSK-3? activity independent of p42/p44 MAPK and p38 activation concomitant with reduced Notch signaling and decreased vSMC proliferation and survival. Exposure of vSMC to changes in medial strain microenvironments in vivo following carotid artery ligation revealed that enhanced GSK-3? activity was predominantly localized to medial and neointimal vSMC concomitant with increased Notch signaling, proliferating nuclear antigen and decreased Bax expression, respectively, as vascular remodeling progressed. GSK-3? is an important modulator of Notch signaling leading to altered vSMC cell growth where low strain/tension microenvironments prevail.
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Alcohol inhibits smooth muscle cell proliferation via regulation of the Notch signaling pathway.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 10-07-2010
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To determine the role of Notch signaling in mediating alcohols inhibition of smooth muscle cell (SMC) proliferation.
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Acute ANIT toxicity in male IL-10 knockout and wild-type mice.
Toxicol Pathol
PUBLISHED: 07-08-2010
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The innate immune response is known to modify hepatocellular injury induced by toxicants. To assess the role of IL-10, a component of the innate immune response, in toxicant-induced injury of biliary epithelium, wild-type (WT) and IL-10 knockout mice (KO) were given a single toxic dose (50 mg/kg) of alpha-napthylisothiocyanate (ANIT) and assessed at twenty-four-hour intervals for four days following treatment. Clinical signs of toxicity were greater in WT mice. Unexpectedly, over the course of the study, there was a consistent tendency for ANIT-treated IL-10 KO mice to have less hepatocellular injury than WT mice. However, changes in the biliary epithelium differed in that there was more histologic evidence of inflammation and necrosis on days 2 and 3, respectively, in ANIT-treated IL-10 KO mice compared with WT mice. Proliferation of biliary epithelium and hepatocytes was greater and/or occurred earlier in the ANIT-treated IL-10 KO mice compared with the ANIT-treated WT mice, suggesting a greater reparative response was needed for recovery after toxicant injury in the IL-10 KO mice. Overall, our data suggest that IL-10 KO mice have less hepatocellular injury than WT mice following a toxic dose of ANIT and that biliary epithelial injury is accentuated in the KO mice.
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Time course gene expression using laser capture microscopy-extracted bile ducts, but not hepatic parenchyma, reveals acute alpha-naphthylisothiocyanate toxicity.
Toxicol Pathol
PUBLISHED: 06-15-2010
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Acute toxic responses to a 50-mg/kg oral dose of 1-naphthylisothiocyanate (ANIT) were evaluated by microarray analysis of laser capture-microdissected rat biliary epithelium or hepatic parenchyma obtained 2 and 6 hours postdose. Distinct differences in gene expression patterns between biliary epithelium and hepatic parenchyma were noted at the 2-hour postdose time point, where 375 genes were altered in biliary epithelium but only 38 genes were altered in hepatic parenchyma. Endoplasmic reticulum stress genes were uniquely expressed in biliary epithelial cells at 2 hours postdose. By 6 hours postdose, 620 genes were altered in biliary epithelium, but only 32 genes were altered in hepatic parenchyma. In biliary epithelium, expression of genes involved in the unfolded protein response had decreased compared with the 2-hour time point, while expression of genes involved in protein degradation such as proteasome-ubquination pathways and cell death pathways had increased. At this same time, hepatic parenchymal gene expression changed little. Within 6 hours following oral exposure to ANIT, prior to morphologic changes, specific biliary epithelial gene expression changes, indicative of a vigorous unfolded protein response with protein destruction and cell death pathway activation were noted, in contrast to minor changes in the hepatic parenchyma.
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Imaging diagnosis--Neuronal ceroid lipofuscinosis with a chronic subdural hematoma.
Vet Radiol Ultrasound
PUBLISHED: 04-21-2010
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A subdural hematoma was found to accompany neuronal ceroid lipofuscinosis in an 11-month-old Dachshund. Results from clinical, magnetic resonance (MR) imaging, histopathologic, ultrastructural, and molecular assessments are described. The dog had a 3-month history of progressive neurologic signs. In MR images, there was severe asymmetric cerebral atrophy with a subdural hematoma. Histopathologically, there was autofluorescent, periodic acid-Schiff-positive lipopigment in neurons and transmission electron microscopy confirmed a typical curvilinear profile of the storage bodies. We hypothesize that rapid brain atrophy contributed to the subdural hematoma formation, a complication not described previously in dogs with neuronal lipofuscinosis.
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Video. Magnetic retraction for NOTES transvaginal cholecystectomy.
Surg Endosc
PUBLISHED: 02-23-2010
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Natural orifice translumenal endoscopic surgery (NOTES) has the potential to decrease the burden of an operation on a patient. Limitations of the endoscopic platform require innovative solutions to provide retraction and create an operation comparable with the gold standard, laparoscopic cholecystectomy.
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Clinical experience with a multifunctional, flexible surgery system for endolumenal, single-port, and NOTES procedures.
Surg Endosc
PUBLISHED: 01-20-2010
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Single-port and incisionless surgical approaches hold the promise of fewer complications, reduced pain, faster recovery, and improved cosmesis compared with traditional open or laparoscopic approaches. The ability to select an access approach (i.e., endolumenal, single-port, transvaginal, or transgastric) with one platform may be important to optimization of individual patient results. The authors report their results using these four separate surgical approaches tailored to three different therapeutic procedures, all with the use of a single flexible platform, the Incisionless Operating Platform (IOP).
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Transrectal endoscopic retrorectal access (TERA): a novel NOTES approach to the peritoneal cavity.
J Laparoendosc Adv Surg Tech A
PUBLISHED: 09-01-2009
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As the field of natural orifice translumenal endoscopic surgery (NOTES) expands, new access sites are being investigated. One access site to the peritoneal cavity, which has not been the subject of much investigation, is transrectal access. The aim of this article is to describe a new method to peritoneal access: transrectal endoscopic retrorectal access (TERA).
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Microarray-based cytogenetic profiling reveals recurrent and subtype-associated genomic copy number aberrations in feline sarcomas.
Chromosome Res.
PUBLISHED: 08-31-2009
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Injection-site-associated sarcomas (ISAS), commonly arising at the site of routine vaccine administration, afflict as many as 22,000 domestic cats annually in the USA. These tumors are typically more aggressive and prone to recurrence than spontaneous sarcomas (non-ISAS), generally receiving a poorer long-term prognosis and warranting a more aggressive therapeutic approach. Although certain clinical and histological factors are highly suggestive of ISAS, timely diagnosis and optimal clinical management may be hindered by the absence of definitive markers that can distinguish between tumors with underlying injection-related etiology and their spontaneous counterpart. Specific nonrandom chromosome copy number aberrations (CNAs) have been associated with the clinical behavior of a vast spectrum of human tumors, providing an extensive resource of potential diagnostic and prognostic biomarkers. Although similar principles are now being applied with great success in other species, their relevance to feline molecular oncology has not yet been investigated in any detail. We report the construction of a genomic microarray platform for detection of recurrent CNAs in feline tumors through cytogenetic assignment of 210 large-insert DNA clones selected at intervals of approximately 15 Mb from the feline genome sequence assembly. Microarray-based profiling of 19 ISAS and 27 non-ISAS cases identified an extensive range of genomic imbalances that were highly recurrent throughout the combined panel of 46 sarcomas. Deletions of two specific regions were significantly associated with the non-ISAS phenotype. Further characterization of these regions may ultimately permit molecular distinction between ISAS and non-ISAS, as a tool for predicting tumor behavior and prognosis, as well as refining means for therapeutic intervention.
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Acetaldehyde stimulates monocyte adhesion in a P-selectin- and TNFalpha-dependent manner.
Atherosclerosis
PUBLISHED: 08-11-2009
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The aim of this study was to determine the effects of acetaldehyde on various steps of the monocyte recruitment cascade.
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Community influences on intimate partner violence in India: Womens education, attitudes towards mistreatment and standards of living.
Soc Sci Med
PUBLISHED: 07-18-2009
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Intimate partner violence (IPV) directed towards women is a serious public health problem. Womens education may offer protection against IPV, but uncertainty exists over how it might reduce risk for IPV at the community and individual levels. The objectives of this study are to: (1) disentangle community from individual-level influences of womens education on risk for IPV; (2) quantify the moderating influence of communities on individual-level associations between womens education and IPV; (3) determine if womens attitudes towards mistreatment and living standards at the community and individual levels account for the protective influence of womens education; and (4) determine if the protective influence of education against IPV is muted among women living in communities exhibiting attitudes more accepting of mistreatment. Study information came from 68,466 married female participants in the National Family Health Survey conducted throughout India in 1998-1999. Multilevel logistic regression was used to address the study objectives. IPV showed substantial clustering at both the state (10.2%) and community levels (11.5%). At the individual level, there was a strong non-linear association between womens education and IPV, partially accounted for by household living standards. The strength of association between womens education and IPV varied from one community to the next with evidence that the acceptance of mistreatment at the community level mutes the protective influence of higher education. Furthermore, womens attitudes towards mistreatment and their standards of living accounted for community-level associations between womens education and IPV. Place of residence accounted for substantial variation in risk of IPV and also modified individual-level associations between IPV and womens education. At the community level, womens education appeared to exert much of its protective influence by altering population attitudes towards the acceptability of mistreatment. However, there was no residual association between womens education and IPV at the community level once living standards are taken into account. While womens education provides strong, independent leverage for reducing the risk of IPV, planners must keep in mind important community factors that modify its protective influence.
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The inflammatory response in transgastric surgery: gastric content leak leads to localized inflammatory response and higher adhesive disease.
Surg Endosc
PUBLISHED: 06-20-2009
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Risk of gastric spillage during transgastric surgery is a potential complication of NOTES procedures. The aim of this study was to determine risk outcomes from gastric spillage in a rat survival model by measuring local and systemic inflammatory markers, adhesive disease, and morbidity.
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Summary of the World Small Animal Veterinary Association standardization committee guide to classification of liver disease in dogs and cats.
Vet. Clin. North Am. Small Anim. Pract.
PUBLISHED: 06-16-2009
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Liver disease is a frequently encountered problem in small animal practice. The World Small Animal Veterinary Association has formed a group of experienced clinicians and pathologists to develop a standardized format for diagnostic terminology. This is hoped to lead to greater uniformity in diagnoses and better communication between clinicians and pathologists alike. The aim is to find a sound scientific basis of diagnostic and treatment protocols for hepatobiliary diseases. This article provides an overview of that monograph.
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The impact of proton-pump inhibitors on intraperitoneal sepsis: a word of caution for transgastric NOTES procedures.
Surg Endosc
PUBLISHED: 05-01-2009
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During transgastric natural orifice transluminal endoscopic surgery (NOTES), there is an iatrogenic perforation of the gastric wall with leakage of gastric contents into the peritoneal cavity. The aim of this study is to determine the effect of proton-pump inhibitors (PPI) and alterations of gastric pH on infection during transgastric surgery.
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Sonic Hedgehog induces Notch target gene expression in vascular smooth muscle cells via VEGF-A.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 04-30-2009
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Notch, VEGF, and components of the Hedgehog (Hh) signaling pathway have been implicated in vascular morphogenesis. The role of Notch in mediating hedgehog control of adult vascular smooth muscle cell (SMC) growth and survival remains unexplored.
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Acquired arteriovenous fistula in a grizzly bear (Ursus arctos horribilis).
J. Zoo Wildl. Med.
PUBLISHED: 04-17-2009
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A captive adult male grizzly bear (Ursus arctos horribilis) was evaluated due to multifocal wounds of the skin and subcutaneous tissues sustained as a result of trauma from another grizzly bear. On presentation, one lesion that was located in the perineal region seemed to be a deep puncture with purple tissue protruding from it. This perineal wound did not heal in the same manner or rate as did the other wounds. Twenty-five days after initial detection, substantial active hemorrhage from the lesion occurred and necessitated anesthesia for examination of the bear. The entire lesion was surgically excised, which later proved curative. An acquired arteriovenous fistula was diagnosed via histopathology. Arteriovenous fistulas can develop after traumatic injury and should be considered as a potential complication in bears with nonhealing wounds.
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Video. NOTES: transvaginal cholecystectomy with assisting articulating instruments.
Surg Endosc
PUBLISHED: 03-13-2009
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Transvaginal cholecystectomy has been performed at several institutions using hybrid natural orifice translumenal endoscopic surgery (NOTES) techniques.
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Aflatoxin B1 and/or hepatitis B virus induced tumor spectrum in a genetically engineered hepatitis B virus expression and Trp53 haploinsufficient mouse model system for hepatocarcinogenesis.
Toxicol Pathol
PUBLISHED: 03-02-2009
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The authors investigated the spectrum of tumors and Trp53 mutations in genetically engineered models using the FVB/N mouse that expressed the hepatitis B virus genome and/or carried a Trp53 null and wildtype allele and/or were exposed to aflatoxin B1. Liver tumor incidence was increased when all three risk factors were present. Without aflatoxin B1 exposure, neither Trp53 haploinsufficiency nor HBV expression affected liver tumor development. Liver tumor prevalence increased with aflatoxin B1 exposure (p < .001), as thirteen of fourteen mice with liver tumors were initiated with aflatoxin B1. Liver tumors were more frequent in males (12/190) than females (2/170). Seventy-three mice developed sarcomas. Trp53 haploinsufficiency was associated with increased sarcoma incidence in males and females (p < .001). In Trp53 haploinsufficient mice, the HBV transgene increased the risk of sarcoma in males and females (p < .001). Lymphoma was significantly increased in Trp53 haploinsufficient FVB/N mice. There was no loss of heterozygosity at the wildtype Trp53 locus in twenty-five sarcomas or four hepatocellular tumors examined. No mutations were identified in the mRNA (exons 2-11) of Trp53 in six liver neoplasms or twenty-four sarcomas. In this model system, HBV expression affected only hepatocellular neoplasia in association with both aflatoxin B1 initiation and p53 haploinsufficiency.
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Natural orifice surgery: initial clinical experience.
Surg Endosc
PUBLISHED: 02-11-2009
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Natural orifice translumenal endoscopic surgery (NOTES) has moved quickly from preclinical investigation to clinical implementation. However, several major technical problems limit clinical NOTES including safe access, retraction and dissection of the gallbladder, and clipping of key structures. This study aimed to identify challenges and develop solutions for NOTES during the initial clinical experience.
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The Brief Child and Family Phone Interview (BCFPI): 2. Usefulness in screening for child and adolescent psychopatholog.
J Child Psychol Psychiatry
PUBLISHED: 01-30-2009
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This study examines the use of the Brief Child and Family Phone Interview (BCFPI) to screen for childhood psychiatric disorder based on Diagnostic Interview Schedule for Children Version IV (DISC-IV) classifications of attention-deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), conduct disorder (CD), separation anxiety (SAD), generalized anxiety (GAD) and major depression (MDD).
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Ventral rectopexy for rectal prolapse and obstructed defecation.
Clin Colon Rectal Surg
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Ventral rectopexy has gained popularity in Europe to treat full-thickness rectal external and internal prolapse. This procedure has been shown to achieve acceptable anatomic results with low recurrence rates, few complications, and improvements of both constipation and fecal incontinence. The authors review the principles, techniques, and outcomes of ventral rectopexy.
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Evaluation of diode endoscopic cyclophotocoagulation in bovine cadaver eyes.
Am. J. Vet. Res.
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To evaluate the anterior chamber approach and energy levels for endoscopic cyclophotocoagulation (ECPC) and assess ECPC-induced tissue damage in phakic eyes of bovine cadavers.
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Effects of Kupffer cell depletion on acute alpha-naphthylisothiocyanate-induced liver toxicity in male mice.
Toxicol Pathol
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Depletion of Kupffer cells, known to modulate chemical-induced hepatocellular injury, has not been studied with regard to biliary epithelial injury. Here, the authors investigated the effect of Kupffer cell depletion by clodronate on the toxicity of alpha-naphthylisothiocyanate (ANIT), known to injure biliary epithelium as well as hepatocytes. Up to 99% depletion of Kupffer cells occurred in ANIT and liposome-encapsulated clodronate-treated mice. The effect of Kupffer cell depletion was most evident one day following ANIT treatment. Histologically, there was a modest increase in neutrophil infiltration of the bile ducts, hepatocytic necrosis, and microvesicular vacuolization in the ANIT and clodronate-treated mice, but differences between other groups did not persist. Clinical pathology analytes related to the biliary or hepatocellular injury were significantly elevated in ANIT and clodronate-treated mice compared to mice given clodronate only. This was also true for mice given ANIT and empty liposomes in the case of the biliary analytes. However, group means were typically higher for the ANIT and clodronate-treated group than others on the first 2 days following ANIT injection. These findings suggest that Kupffer cell reduction increases hepatobiliary damage due to ANIT treatment.
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Reyes or Reyes-like syndrome in western lowland gorilla (Gorilla gorilla gorilla).
J. Med. Primatol.
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A 15-year-old western lowland gorilla (Gorilla gorilla gorilla) died shortly after transfer to the North Carolina Zoo.
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Limited yield of diagnoses of intrahepatic infectious causes of canine granulomatous hepatitis from archival liver tissue.
J. Vet. Diagn. Invest.
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Canine granulomatous hepatitis is an uncommon morphologic diagnosis that has been associated with a variety of diseases, including a number of systemic infectious etiologies. Formalin-fixed, paraffin-embedded (FFPE) tissues are typically the only source of liver tissue remaining for additional testing for the presence of infectious disease within granulomas. It is unclear if the more common infectious culprits of granulomatous hepatitis can be identified from such specimens. The aim of the current study was to retrospectively investigate archival FFPE liver tissue from dogs with granulomatous hepatitis for the presence of infectious agents. Semiquantitative analysis of copper accumulation in liver specimens was also performed. Medical records were examined for recorded evidence of systemic infectious disease diagnosis. Formalin-fixed, paraffin-embedded liver was prospectively evaluated for infectious agents via differential staining techniques (n = 13), eubacterial fluorescent in situ hybridization (n = 11), and Bartonella polymerase chain reaction assays (n = 15). An infectious cause of granulomatous hepatitis was not identified within liver tissue from any dog using these diagnostic methodologies. Six out of 25 (24%) dogs were diagnosed with concurrent systemic or localized bacterial infections at the time of presentation. Nine out of 17 (53%) dogs had excessive hepatic copper accumulation when evaluated by a semiquantitative histologic grading scheme or quantitative copper analysis. As definitive infectious causes of granulomatous hepatitis were not identified within archival liver biopsy samples, it was concluded that investigation of infectious etiologies within FFPE liver specimens using these diagnostic approaches may be of low yield.
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Immunohistochemical and immunopathologic characterization of superficial stromal immune-mediated keratitis in horses.
Am. J. Vet. Res.
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To describe the immunopathologic characteristics of superficial stromal immune-mediated keratitis (IMMK) immunopathologically by characterizing cellular infiltrate in affected corneas of horses.
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Diode laser endoscopic cyclophotocoagulation in the normal equine eye.
Vet Ophthalmol
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To determine the clinical and histologic effects of diode endoscopic cyclophotocoagulation (ECP) in the phakic equine eye.
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The MTAP-CDKN2A locus confers susceptibility to a naturally occurring canine cancer.
Cancer Epidemiol. Biomarkers Prev.
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Advantages offered by canine population substructure, combined with clinical presentations similar to human disorders, makes the dog an attractive system for studies of cancer genetics. Cancers that have been difficult to study in human families or populations are of particular interest. Histiocytic sarcoma is a rare and poorly understood neoplasm in humans that occurs in 15% to 25% of Bernese Mountain Dogs (BMD).
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Serology-enabled discovery of genetically diverse hepaciviruses in a new host.
J. Virol.
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Genetic and biological characterization of new hepaciviruses infecting animals contributes to our understanding of the ultimate origins of hepatitis C virus (HCV) infection in humans and dramatically enhances our ability to study its pathogenesis using tractable animal models. Animal homologs of HCV include a recently discovered canine hepacivirus (CHV) and GB virus B (GBV-B), both viruses with largely undetermined natural host ranges. Here we used a versatile serology-based approach to determine the natural host of the only known nonprimate hepacivirus (NPHV), CHV, which is also the closest phylogenetic relative of HCV. Recombinant protein expressed from the helicase domain of CHV NS3 was used as antigen in the luciferase immunoprecipitation system (LIPS) assay to screen several nonprimate animal species. Thirty-six samples from 103 horses were immunoreactive, and viral genomic RNA was present in 8 of the 36 seropositive animals and none of the seronegative animals. Complete genome sequences of these 8 genetically diverse NPHVs showed 14% (range, 6.4% to 17.2%) nucleotide sequence divergence, with most changes occurring at synonymous sites. RNA secondary structure prediction of the 383-base 5 untranslated region of NPHV was refined and extended through mapping of polymorphic sites to unpaired regions or (semi)covariant pairings. Similar approaches were adopted to delineate extensive RNA secondary structures in the coding region of the genome, predicted to form 27 regularly spaced, thermodynamically stable stem-loops. Together, these findings suggest a promising new nonprimate animal model and provide a database that will aid creation of functional NPHV cDNA clones and other novel tools for hepacivirus studies.
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The implementation of a self-consistent constricted variational density functional theory for the description of excited states.
J Chem Phys
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We present here the implementation of a self-consistent approach to the calculation of excitation energies within regular Kohn-Sham density functional theory. The method is based on the n-order constricted variational density functional theory (CV(n)-DFT) [T. Ziegler, M. Seth, M. Krykunov, J. Autschbach, and F. Wang, J. Chem. Phys. 130, 154102 (2009)] and its self-consistent formulation (SCF-CV(?)-DFT) [J. Cullen, M. Krykunov, and T. Ziegler, Chem. Phys. 391, 11 (2011)]. A full account is given of the way in which SCF-CV(?)-DFT is implemented. The SCF-CV(?)-DFT scheme is further applied to transitions from occupied ? orbitals to virtual ?(?) orbitals. The same series of transitions has been studied previously by high-level ab initio methods. We compare here the performance of SCF-CV(?)-DFT to that of time dependent density functional theory (TD-DFT), CV(n)-DFT and ?SCF-DFT, with the ab initio results as a benchmark standard. It is finally demonstrated how adiabatic TD-DFT and ?SCF-DFT are related through different approximations to SCF-CV(?)-DFT.
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