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  1. 3D hepatic cultures simultaneously maintain primary hepatocyte and liver sinusoidal endothelial cell phenotypes.

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    Yeonhee Kim

    Full Text Available Developing in vitro engineered hepatic tissues that exhibit stable phenotype is a major challenge in the field of hepatic tissue engineering. However, the rapid dedifferentiation of hepatic parenchymal (hepatocytes and non-parenchymal (liver sinusoidal endothelial, LSEC cell types when removed from their natural environment in vivo remains a major obstacle. The primary goal of this study was to demonstrate that hepatic cells cultured in layered architectures could preserve or potentially enhance liver-specific behavior of both cell types. Primary rat hepatocytes and rat LSECs (rLSECs were cultured in a layered three-dimensional (3D configuration. The cell layers were separated by a chitosan-hyaluronic acid polyelectrolyte multilayer (PEM, which served to mimic the Space of Disse. Hepatocytes and rLSECs exhibited several key phenotypic characteristics over a twelve day culture period. Immunostaining for the sinusoidal endothelial 1 antibody (SE-1 demonstrated that rLSECs cultured in the 3D hepatic model maintained this unique feature over twelve days. In contrast, rLSECs cultured in monolayers lost their phenotype within three days. The unique stratified structure of the 3D culture resulted in enhanced heterotypic cell-cell interactions, which led to improvements in hepatocyte functions. Albumin production increased three to six fold in the rLSEC-PEM-Hepatocyte cultures. Only rLSEC-PEM-Hepatocyte cultures exhibited increasing CYP1A1/2 and CYP3A activity. Well-defined bile canaliculi were observed only in the rLSEC-PEM-Hepatocyte cultures. Together, these data suggest that rLSEC-PEM-Hepatocyte cultures are highly suitable models to monitor the transformation of toxins in the liver and their transport out of this organ. In summary, these results indicate that the layered rLSEC-PEM-hepatocyte model, which recapitulates key features of hepatic sinusoids, is a potentially powerful medium for obtaining comprehensive knowledge on liver metabolism

  2. Reciprocal regulation between O-GlcNAcylation and tribbles pseudokinase 2 (TRIB2) maintains transformative phenotypes in liver cancer cells.

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    Yao, Bingjie; Xu, Yanli; Wang, Jiayi; Qiao, Yongxia; Zhang, Yue; Zhang, Xiao; Chen, Yan; Wu, Qi; Zhao, Yinghui; Zhu, Guoqing; Sun, Fenyong; Li, Zhi; Yuan, Hong

    2016-11-01

    TRIB2 has been identified as an onco-protein, and O-GlcNAcylation of target proteins has been reported to stimulate transformative phenotypes in liver cancer cells. However, the relationships between TRIB2 and O-GlcNAcylation are still unknown. The aim of this study was to investigate whether and how O-GlcNAcylation and TRIB2 regulate each other. We found that stimulation of O-GlcNAcylation elevates TRIB2 by enhancing its protein stability. TRIB2 can be O-GlcNAcylated by the hexosamine biosynthesis pathway (HBP). Also, O-GlcNAcylation boosting of transformative phenotypes of liver cancer cells might occur in a TRIB2-dependent manner. Interestingly, TRIB2 stimulated the metabolism of HBP, demonstrating that TRIB2 has positive feedback on O-GlcNAcylation. Notably, TRIB2 was found to maintain the stability of guanylate cyclase 1 alpha 3 (GUCY1A3), a key component of HBP, by interacting GUCY1A3 and reducing its ubiquitination. Importantly, TRIB2-dependent regulation of metabolism, transformative phenotypes, and O-GlcNAcylation all rely on GUCY1A3. Mouse experiments demonstrate that O-GlcNAcylation of TRIB2 is much higher in the livers of diabetic mice compared to control mice, suggesting that O-GlcNAcylation of TRIB2 might be critical for diabetes-associated liver cancer. Collectively, we have uncovered a positive auto-regulatory feedback between O-GlcNAcylation and TRIB2, which might be regarded as a promising therapeutic target for liver cancer.

  3. Phenotypes and Pathology of Drug-Induced Liver Disease.

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    Goodman, Zachary D

    2017-02-01

    Drug hepatotoxicity can simulate nearly any clinical syndrome or pathologic lesion that may occur in the liver, so clinical and histopathologic diagnosis of drug-induced liver injury may be difficult. Nevertheless, most drugs that are known to idiosyncratic liver injury tend to cause patterns of injury that produce characteristic phenotypes. Recognition of these patterns or phenotypes in liver biopsy material is helpful in evaluation of clinical cases of suspected drug-induced liver injury.

  4. Memory CD8 T cells specific for liver stage antigens maintain protracted protection against malaria

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    Urszula eKrzych

    2012-12-01

    Full Text Available Immunologic memory induced by pathogenic agents or vaccinations is inextricably linked to long-lasting protection. Adequately maintained memory T and B cell pools assure a fast, effective and specific response against re-infections. Studies of immune responses amongst residents of malaria endemic areas suggest that memory responses to Plasmodia antigens appear to be neither adequately developed nor maintained, because persons who survive episodes of childhood malaria remain vulnerable to persistent or intermittent malaria infections. By contrast, multiple exposures of humans and laboratory rodents to radiation-attenuated Plasmodia sporozoites (γ-spz induces sterile and long-lasting protection against experimental sporozoite challenge. Protection is associated with MHC class I-dependent CD8 T cells, the key effectors against pre-erythrocytic stage infection. We have adopted the P. berghei γ-spz mouse model to study memory CD8 T cells that are specific for antigens expressed by Pb liver-stage (LS parasites and are found predominantly in the liver. On the basis of phenotypic and functional characteristics, we have demonstrated that liver CD8 T cells form two subsets: CD44hiCD62LloKLRG-1+CD107+CD127-CD122loCD8 T effector/effector memory (TE/EM cells that are the dominant IFN-γ producers and CD44hiCD62LhiKLRG-1-CD107-CD127+CD122hiCD8 T central memory (TCM cells. In this review, we discuss our observations concerning the role of CD8 TE/EM and CD8 TCM cells in the maintenance of protracted protective immunity against experimental malaria infection. Finally, we present a hypothesis consistent with a model whereby intrahepatic CD8 TCM cells, that are maintained in part by LS-Ag depot and by IL-15-mediated survival and homeostatic proliferation, form a reservoir of cells ready for conscription to CD8 TE/EM cells needed to prevent re-infections.

  5. Mesenchymal stem cells maintain TGF-beta-mediated chondrogenic phenotype in alginate bead culture

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    Mehlhorn, A T; Schmal, H; Kaiser, S

    2006-01-01

    This article addresses the stability of chondrogenic phenotype and the transdifferentiation potential of bone marrow-derived mesenchymal stem cells (MSCs) at distinct stages of differentiation. Differentiated MSCs were expected to maintain cartilage-like gene expression pattern in the absence of ...

  6. Altering an extended phenotype reduces intraspecific male aggression and can maintain diversity in cichlid fish

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    Isabel Santos Magalhaes

    2013-11-01

    Full Text Available Reduced male aggression towards different phenotypes generating negative frequency-dependent intrasexual selection has been suggested as a mechanism to facilitate the invasion and maintenance of novel phenotypes in a population. To date, the best empirical evidence for the phenomenon has been provided by laboratory studies on cichlid fish with different colour polymorphisms. Here we experimentally tested the hypothesis in a natural population of Lake Malawi cichlid fish, in which males build sand-castles (bowers to attract females during seasonal leks. We predicted that if bower shape plays an important role in male aggressive interactions, aggression among conspecific males should decrease when their bower shape is altered. Accordingly, we allocated randomly chosen bowers in a Nyassachromis cf. microcephalus lek into three treatments: control, manipulated to a different shape, and simulated manipulation. We then measured male behaviours and bower shape before and after these treatments. We found that once bower shape was altered, males were involved in significantly fewer aggressive interactions with conspecific males than before manipulation. Mating success was not affected. Our results support the idea that an extended phenotype, such as bower shape, can be important in maintaining polymorphic populations. Specifically, reduced male conspecific aggression towards males with different extended phenotypes (here, bower shapes may cause negative frequency-dependent selection, allowing the invasion and establishment of a new phenotype (bower builder. This could help our understanding of mechanisms of diversification within populations, and in particular, the overall diversification of bower shapes within Lake Malawi cichlids.

  7. Liver BCATm transgenic mouse model reveals the important role of the liver in maintaining BCAA homeostasis.

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    Ananieva, Elitsa A; Van Horn, Cynthia G; Jones, Meghan R; Hutson, Susan M

    2017-02-01

    Unlike other amino acids, the branched-chain amino acids (BCAAs) largely bypass first-pass liver degradation due to a lack of hepatocyte expression of the mitochondrial branched-chain aminotransferase (BCATm). This sets up interorgan shuttling of BCAAs and liver-skeletal muscle cooperation in BCAA catabolism. To explore whether complete liver catabolism of BCAAs may impact BCAA shuttling in peripheral tissues, the BCATm gene was stably introduced into mouse liver. Two transgenic mouse lines with low and high hepatocyte expression of the BCATm transgene (LivTg-LE and LivTg-HE) were created and used to measure liver and plasma amino acid concentrations and determine whether the first two BCAA enzymatic steps in liver, skeletal muscle, heart and kidney were impacted. Expression of the hepatic BCATm transgene lowered the concentrations of hepatic BCAAs while enhancing the concentrations of some nonessential amino acids. Extrahepatic BCAA metabolic enzymes and plasma amino acids were largely unaffected, and no growth rate or body composition differences were observed in the transgenic animals as compared to wild-type mice. Feeding the transgenic animals a high-fat diet did not reverse the effect of the BCATm transgene on the hepatic BCAA catabolism, nor did the high-fat diet cause elevation in plasma BCAAs. However, the high-fat-diet-fed BCATm transgenic animals experienced attenuation in the mammalian target of rapamycin (mTOR) pathway in the liver and had impaired blood glucose tolerance. These results suggest that complete liver BCAA metabolism influences the regulation of glucose utilization during diet-induced obesity.

  8. Magnetically levitated mesenchymal stem cell spheroids cultured with a collagen gel maintain phenotype and quiescence

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    Natasha S Lewis

    2017-04-01

    Full Text Available Multicellular spheroids are an established system for three-dimensional cell culture. Spheroids are typically generated using hanging drop or non-adherent culture; however, an emerging technique is to use magnetic levitation. Herein, mesenchymal stem cell spheroids were generated using magnetic nanoparticles and subsequently cultured within a type I collagen gel, with a view towards developing a bone marrow niche environment. Cells were loaded with magnetic nanoparticles, and suspended beneath an external magnet, inducing self-assembly of multicellular spheroids. Cells in spheroids were viable and compared to corresponding monolayer controls, maintained stem cell phenotype and were quiescent. Interestingly, core spheroid necrosis was not observed, even with increasing spheroid size, in contrast to other commonly used spheroid systems. This mesenchymal stem cell spheroid culture presents a potential platform for modelling in vitro bone marrow stem cell niches, elucidating interactions between cells, as well as a useful model for drug delivery studies.

  9. Regulatory T cells expanded from HIV-1-infected individuals maintain phenotype, TCR repertoire and suppressive capacity.

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    Mathieu Angin

    Full Text Available While modulation of regulatory T cell (Treg function and adoptive Treg transfer are being explored as therapeutic modalities in the context of autoimmune diseases, transplantation and cancer, their role in HIV-1 pathogenesis remains less well defined. Controversy persists regarding their beneficial or detrimental effects in HIV-1 disease, which warrants further detailed exploration. Our objectives were to investigate if functional CD4(+ Tregs can be isolated and expanded from HIV-1-infected individuals for experimental or potential future therapeutic use and to determine phenotype and suppressive capacity of expanded Tregs from HIV-1 positive blood and tissue. Tregs and conventional T cell controls were isolated from blood and gut-associated lymphoid tissue of individuals with HIV-1 infection and healthy donors using flow-based cell-sorting. The phenotype of expanded Tregs was assessed by flow-cytometry and quantitative PCR. T-cell receptor ß-chain (TCR-β repertoire diversity was investigated by deep sequencing. Flow-based T-cell proliferation and chromium release cytotoxicity assays were used to determine Treg suppressive function. Tregs from HIV-1 positive individuals, including infants, were successfully expanded from PBMC and GALT. Expanded Tregs expressed high levels of FOXP3, CTLA4, CD39 and HELIOS and exhibited a highly demethylated TSDR (Treg-specific demethylated region, characteristic of Treg lineage. The TCRß repertoire was maintained following Treg expansion and expanded Tregs remained highly suppressive in vitro. Our data demonstrate that Tregs can be expanded from blood and tissue compartments of HIV-1+ donors with preservation of Treg phenotype, function and TCR repertoire. These results are highly relevant for the investigation of potential future therapeutic use, as currently investigated for other disease states and hold great promise for detailed studies on the role of Tregs in HIV-1 infection.

  10. Functional link between ETB receptors and eNOS maintain tissue oxygenation in the normal liver.

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    Paxian, Markus; Keller, Steve A; Baveja, Rajiv; Korneszczuk, Katarzyna; Huynh, Toan T; Clemens, Mark G

    2004-01-01

    Endothelins and their receptors play a crucial role in regulating liver microcirculation in pathophysiological conditions. The authors investigated the functional significance of the coupling of ET(B) receptors and eNOS in maintaining regional perfusion and tissue oxygenation in the normal liver. The effect of endothelin-1 or the ET(B) agonist IRL1620 on oxygen consumption was determined in isolated perfused liver and isolated hepatocytes. Oxygen delivery to the liver tissue was determined in vivo. Following eNOS or iNOS blockade, either ET-1 or IRL1620 was infused via the portal vein. Hepatic tissue oxygenation, redox state, and microcirculation were investigated by intravital microscopy. Injury was estimated by serum LDH. Although IRL1620 and endothelin-1 increased oxygen consumption in isolated hepatocytes, in intact liver, endothelin decreased oxygen consumption while IRL1620 produced no change. In vivo, ET(B) stimulation modestly altered hepatic tissue P(O(2)), redox potential, and microcirculation. eNOS inhibition and ET(B) activation dramatically reduced microcirculatory blood flow, oxygen supply, and increased LDH release. Inhibition of iNOS resulted in small but not significant changes in these parameters. Concomitant ET(A)/ET(B) receptor activation increased microcirculatory failure and decreased tissue oxygen even without NOS inhibition. In contrast, hepatocellular injury was significantly increased following eNOS inhibition. Coupling between ET(B) receptor stimulation and eNOS activation decreases sinusoidal constriction and plays a functionally important role in maintaining microcirculation and tissue oxygenation in the normal liver.

  11. Phenotypic changes of human cells in human-rat liver during partial hepatectomy-induced regeneration

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    Yan Sun; Dong Xiao; Hong-An Li; Jin-Fang Jiang; Qing Li; Ruo-Shuang Zhang; Xi-Gu Chen

    2009-01-01

    AIM: To examine the human hepatic parenchymal and stromal components in rat liver and the phenotypic changes of human cells in liver of human-rat chimera (HRC) generated by in utero transplantation of human cells during partial hepatectomy (PHx)-induced liver regeneration. METHODS: Human hepatic parenchymal and stromal components and phenotypic changes of human cells during liver regeneration were examined by flow cytometry, in situ hybridization and immunohistochemistry. RESULTS: ISH analysis demonstrated human Alupositive cells in hepatic parenchyma and stroma of recipient liver. Functional human hepatocytes generated in this model potentially constituted human hepatic functional units with the presence of donor-derived human endothelial and biliary duct cells in host liver. Alpha fetoprotein (AFP)+, CD34+ and CD45+ cells were observed in the chimeric liver on day 10 after PHxinduced liver regeneration and then disappeared in PHx group, but not in non-PHx group, suggesting that dynamic phenotypic changes of human cells expressing AFP, CD34 and CD45 cells may occur during the chimeric liver regeneration. Additionally, immunostaining for human proliferating cell nuclear antigen (PCNA) showed that the number of PCNA-positive cells in the chimeric liver of PHx group was markedly increased, as compared to that of control group, indicating that donor-derived human cells are actively proliferated during PHx-induced regeneration of HRC liver.

  12. Effect of a High-Fructose Weight-Maintaining Diet on Lipogenesis and Liver Fat.

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    Schwarz, Jean-Marc; Noworolski, Susan M; Wen, Michael J; Dyachenko, Artem; Prior, Jessica L; Weinberg, Melissa E; Herraiz, Laurie A; Tai, Viva W; Bergeron, Nathalie; Bersot, Thomas P; Rao, Madhu N; Schambelan, Morris; Mulligan, Kathleen

    2015-06-01

    Consumption of high-fructose diets promotes hepatic fatty acid synthesis (de novo lipogenesis [DNL]) and an atherogenic lipid profile. It is unclear whether these effects occur independent of positive energy balance and weight gain. We compared the effects of a high-fructose, (25% of energy content) weight-maintaining diet to those of an isocaloric diet with the same macronutrient distribution but in which complex carbohydrate (CCHO) was substituted for fructose. Eight healthy men were studied as inpatients for consecutive 9-day periods. Stable isotope tracers were used to measure fractional hepatic DNL and endogenous glucose production (EGP) and its suppression during a euglycemic-hyperinsulinemic clamp. Liver fat was measured by magnetic resonance spectroscopy. Weight remained stable. Regardless of the order in which the diets were fed, the high-fructose diet was associated with both higher DNL (average, 18.6 ± 1.4% vs 11.0 ± 1.4% for CCHO; P = .001) and higher liver fat (median, +137% of CCHO; P = .016) in all participants. Fasting EGP and insulin-mediated glucose disposal did not differ significantly, but EGP during hyperinsulinemia was greater (0.60 ± 0.07 vs 0.46 ± 0.06 mg/kg/min; P = .013) with the high-fructose diet, suggesting blunted suppression of EGP. Short-term high-fructose intake was associated with increased DNL and liver fat in healthy men fed weight-maintaining diets.

  13. Nrf2 is involved in maintaining hepatocyte identity during liver regeneration.

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    Yuhong Zou

    Full Text Available Nrf2, a central regulator of the cellular defense against oxidative stress and inflammation, participates in modulating hepatocyte proliferation during liver regeneration. It is not clear, however, whether Nrf2 regulates hepatocyte growth, an important cellular mechanism to regain the lost liver mass after partial hepatectomy (PH. To determine this, various analyses were performed in wild-type and Nrf2-null mice following PH. We found that, at 60 h post-PH, the vast majority of hepatocytes lacking Nrf2 reduced their sizes, activated hepatic progenitor markers (CD133, TWEAK receptor, and trefoil factor family 3, depleted HNF4α protein, and downregulated the expression of a group of genes critical for their functions. Thus, the identity of hepatocytes deficient in Nrf2 was transiently but massively impaired in response to liver mass loss. This event was associated with the coupling of protein depletion of hepatic HNF4α, a master regulator of hepatocyte differentiation, and concomitant inactivation of hepatic Akt1 and p70S6K, critical hepatocyte growth signaling molecules. We conclude that Nrf2 participates in maintaining newly regenerated hepatocytes in a fully differentiated state by ensuring proper regulation of HNF4α, Akt1, and p70S6K during liver regeneration.

  14. A Convenient and Efficient Method to Enrich and Maintain Highly Proliferative Human Fetal Liver Stem Cells.

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    Guo, Xuan; Wang, Shu; Dou, Ya-ling; Guo, Xiang-fei; Chen, Zhao-li; Wang, Xin-wei; Shen, Zhi-qiang; Qiu, Zhi-gang; Jin, Min; Li, Jun-wen

    2015-06-01

    Pluripotent human hepatic stem cells have broad research and clinical applications, which are, however, restricted by both limited resources and technical difficulties with respect to isolation of stem cells from the adult or fetal liver. In this study, we developed a convenient and efficient method involving a two-step in situ collagenase perfusion, gravity sedimentation, and Percoll density gradient centrifugation to enrich and maintain highly proliferative human fetal liver stem cells (hFLSCs). Using this method, the isolated hFLSCs entered into the exponential growth phase within 10 days and maintained sufficient proliferative activity to permit subculture for at least 20 passages without differentiation. Immunocytochemistry, immunofluorescence, and flow cytometry results showed that these cells expressed stem cell markers, such as c-kit, CD44, epithelial cell adhesion molecule (EpCAM), oval cell marker-6 (OV-6), epithelial marker cytokeratin 18 (CK18), biliary ductal marker CK19, and alpha-fetoprotein (AFP). Gene expression analysis showed that these cells had stable mRNA expression of c-Kit, EpCAM, neural cell adhesion molecule (NCAM), CK19, CK18, AFP, and claudin 3 (CLDN-3) throughout each passage while maintaining low levels of ALB, but with complete absence of cytochrome P450 3A4 (C3A4), phosphoenolpyruvate carboxykinase (PEPCK), telomeric repeat binding factor (TRF), and connexin 26 (CX26) expression. When grown in appropriate medium, these isolated liver stem cells could differentiate into hepatocytes, cholangiocytes, osteoblasts, adipocytes, or endothelial cells. Thus, we have demonstrated a more economical and efficient method to isolate hFLSCs than magnetic-activated cell sorting (MACS). This novel approach may provide an excellent tool to isolate highly proliferative hFLSCs for tissue engineering and regenerative therapies.

  15. Transgenic Chickens Overexpressing Aromatase Have High Estrogen Levels but Maintain a Predominantly Male Phenotype.

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    Lambeth, Luke S; Morris, Kirsten R; Wise, Terry G; Cummins, David M; O'Neil, Terri E; Cao, Yu; Sinclair, Andrew H; Doran, Timothy J; Smith, Craig A

    2016-01-01

    Estrogens play a key role in sexual differentiation of both the gonads and external traits in birds. The production of estrogen occurs via a well-characterized steroidogenic pathway, which is a multistep process involving several enzymes, including cytochrome P450 aromatase. In chicken embryos, the aromatase gene (CYP19A1) is expressed female-specifically from the time of gonadal sex differentiation. Ectopic overexpression of aromatase in male chicken embryos induces gonadal sex reversal, and male embryos treated with estradiol become feminized; however, this is not permanent. To test whether a continuous supply of estrogen in adult chickens could induce stable male to female sex reversal, 2 transgenic male chickens overexpressing aromatase were generated using the Tol2/transposase system. These birds had robust ectopic aromatase expression, which resulted in the production of high serum levels of estradiol. Transgenic males had female-like wattle and comb growth and feathering, but they retained male weights, displayed leg spurs, and developed testes. Despite the small sample size, this data strongly suggests that high levels of circulating estrogen are insufficient to maintain a female gonadal phenotype in adult birds. Previous observations of gynandromorph birds and embryos with mixed sex chimeric gonads have highlighted the role of cell autonomous sex identity in chickens. This might imply that in the study described here, direct genetic effects of the male chromosomes largely prevailed over the hormonal profile of the aromatase transgenic birds. This data therefore support the emerging view of at least partial cell autonomous sex development in birds. However, a larger study will confirm this intriguing observation.

  16. Oncogenic driver genes and the inflammatory microenvironment dictate liver tumor phenotype

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    Matter, Matthias S; Marquardt, Jens U; Andersen, Jesper B

    2016-01-01

    The majority of hepatocellular carcinoma (HCC) develops in the background of chronic liver inflammation caused by viral hepatitis and alcoholic or non-alcoholic steatohepatitis. However, the impact of different types of chronic inflammatory microenvironments on the phenotypes of tumors generated...

  17. Gene-metabolite network analysis in different nonalcoholic fatty liver disease phenotypes

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    Liu, Xiao-Lin; Ming, Ya-Nan; Zhang, Jing-Yi; Chen, Xiao-Yu; Zeng, Min-De; Mao, Yi-Min

    2017-01-01

    We sought to identify common key regulators and build a gene-metabolite network in different nonalcoholic fatty liver disease (NAFLD) phenotypes. We used a high-fat diet (HFD), a methionine-choline-deficient diet (MCDD) and streptozocin (STZ) to establish nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH) and NAFL+type 2 diabetes mellitus (T2DM) in rat models, respectively. Transcriptomics and metabolomics analyses were performed in rat livers and serum. A functional network-based regulation model was constructed using Cytoscape with information derived from transcriptomics and metabolomics. The results revealed that 96 genes, 17 liver metabolites and 4 serum metabolites consistently changed in different NAFLD phenotypes (>2-fold, PGene-metabolite network analysis identified ccl2 and jun as hubs with the largest connections to other genes, which were mainly involved in tumor necrosis factor, P53, nuclear factor-kappa B, chemokine, peroxisome proliferator activated receptor and Toll-like receptor signaling pathways. The specifically regulated genes and metabolites in different NAFLD phenotypes constructed their own networks, which were mainly involved in the lipid and fatty acid metabolism in HFD models, the inflammatory and immune response in MCDD models, and the AMPK signaling pathway and response to insulin in HFD+STZ models. Our study identified networks showing the general and specific characteristics in different NAFLD phenotypes, complementing the genetic and metabolic features in NAFLD with hepatic and extra-hepatic manifestations. PMID:28082742

  18. Hepatic phenotype of liver fatty acid binding protein gene-ablated mice

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    Martin, Gregory G.; Atshaves, Barbara P.; Huang, Huan; McIntosh, Avery L.; Williams, Brad J.; Pai, Pei-Jing; Russell, David H.; Kier, Ann B.; Schroeder, Friedhelm

    2009-01-01

    Although the function of liver fatty acid binding protein in hepatic fatty acid metabolism has been extensively studied, its potential role in hepatic cholesterol homeostasis is less clear. Although hepatic cholesterol accumulation was initially reported in L-FABP-null female mice, that study was performed with early N2 backcross generation mice. To resolve whether the hepatic cholesterol phenotype in these L-FABP−/− mice was attributable to genetic inhomogeneity, these L-FABP−/− mice were fu...

  19. Liver cirrhosis in patients newly diagnosed with neurological phenotype of Wilson's disease.

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    Przybyłkowski, Adam; Gromadzka, Grażyna; Chabik, Grzegorz; Wierzchowska, Agata; Litwin, Tomasz; Członkowska, Anna

    2014-01-01

    Wilson's disease (WD) can manifest itself in different clinical forms, the neurological and hepatic ones being the most common. It is suggested that neurological signs and psychiatric symptoms develop secondary to liver involvement. The aim of this study was to characterize the liver disease in patients newly diagnosed with the neurological form of WD. Treatment-naive patients diagnosed with WD were classified into three phenotypic groups: hepatic, neurological and pre-symptomatic. Liver involvement was ascertained through surrogate markers: abdominal ultrasound and laboratory parameters. In addition, study participants were screened for esophageal varices. Of 53 consecutively diagnosed WD patients, 23 individuals (43.4%) had a predominantly neurological presentation. In this group, cirrhosis was diagnosed in 11 (47.8%) subjects. Esophageal varices were present in all of them. In every patient with neurological WD, there was at least one sign of hepatic disease on ultrasound examination, indicating universal presence of liver involvement. The prevalence of surrogate signs of cirrhosis was similar in patients with the neurological and in those with the hepatic phenotype.

  20. SIRT1 Overexpression Maintains Cell Phenotype and Function of Endothelial Cells Derived from Induced Pluripotent Stem Cells.

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    Jiang, Bin; Jen, Michele; Perrin, Louisiane; Wertheim, Jason A; Ameer, Guillermo A

    2015-12-01

    Endothelial cells (ECs) that are differentiated from induced pluripotent stem cells (iPSCs) can be used in establishing disease models for personalized drug discovery or developing patient-specific vascularized tissues or organoids. However, a number of technical challenges are often associated with iPSC-ECs in culture, including instability of the endothelial phenotype and limited cell proliferative capacity over time. Early senescence is believed to be the primary mechanism underlying these limitations. Sirtuin1 (SIRT1) is an NAD(+)-dependent deacetylase involved in the regulation of cell senescence, redox state, and inflammatory status. We hypothesize that overexpression of the SIRT1 gene in iPSC-ECs will maintain EC phenotype, function, and proliferative capacity by overcoming early cell senescence. SIRT1 gene was packaged into a lentiviral vector (LV-SIRT1) and transduced into iPSC-ECs at passage 4. Beginning with passage 5, iPSC-ECs exhibited a fibroblast-like morphology, whereas iPSC-ECs overexpressing SIRT1 maintained EC cobblestone morphology. SIRT1 overexpressing iPSC-ECs also exhibited a higher percentage of canonical markers of endothelia (LV-SIRT1 61.8% CD31(+) vs. LV-empty 31.7% CD31(+), P cell lifespan, overcoming critical hurdles associated with the use of iPSC-ECs in translational research.

  1. Rapamycin Maintains the Chondrocytic Phenotype and Interferes with Inflammatory Cytokine Induced Processes

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    Andrea De Luna-Preitschopf

    2017-07-01

    Full Text Available Osteoarthritis (OA is hallmarked by a progressive degradation of articular cartilage. Besides risk factors including trauma, obesity or genetic predisposition, inflammation has a major impact on the development of this chronic disease. During the course of inflammation, cytokines such as tumor necrosis factor-alpha(TNF-α and interleukin (IL-1β are secreted by activated chondrocytes as well as synovial cells and stimulate the production of other inflammatory cytokines and matrix degrading enzymes. The mTORC1 inhibitor rapamycin is a clinical approved immunosuppressant and several studies also verified its chondroprotective effects in OA. However, the effect of blocking the mechanistic target of rapamycin complex (mTORC1 on the inflammatory status within OA is not well studied. Therefore, we aimed to investigate if inhibition of mTORC1 by rapamycin can preserve and sustain chondrocytes in an inflammatory environment. Patient-derived chondrocytes were cultured in media supplemented with or without the mTORC1 inhibitor rapamycin. To establish an inflammatory environment, either TNF-α or IL-1β was added to the media (=OA-model. The chondroprotective and anti-inflammatory effects of rapamycin were evaluated using sulfated glycosaminoglycan (sGAG release assay, Caspase 3/7 activity assay, lactate dehydrogenase (LDH assay and quantitative real time polymerase chain reaction (PCR. Blocking mTORC1 by rapamycin reduced the release and therefore degradation of sGAGs, which are components of the extracellular matrix secreted by chondrocytes. Furthermore, blocking mTORC1 in OA chondrocytes resulted in an enhanced expression of the main chondrogenic markers. Rapamycin was able to protect chondrocytes from cell death in an OA-model shown by reduced Caspase 3/7 activity and diminished LDH release. Furthermore, inhibition of mTORC1 preserved the chondrogenic phenotype of OA chondrocytes, but also reduced inflammatory processes within the OA-model. This study

  2. Brain tumor stem cells maintain overall phenotype and tumorigenicity after in vitro culturing in serum-free conditions

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    Vik-Mo, Einar Osland; Sandberg, Cecilie; Olstorn, Havard; Varghese, Mercy; Brandal, Petter; Ramm-Pettersen, Jon; Murrell, Wayne; Langmoen, Iver Arne

    2010-01-01

    Traditional in vitro culturing of tumor cells has been shown to induce changes so that cultures no longer represent the tumor of origin. Serum-free culturing conditions are used in a variety of cancers to propagate stem-like cells in vitro. Limited reports, however, exist on the effects of such propagation. We have compared cells from brain tumor biopsies cultivated under serum-free conditions at passages 2 and 10 to describe the effects of in vitro culturing. We were able to establish cell lines from 7 of 10 biopsies from patients with glioblastoma. The cell lines adapted to conditions and had 2.2 times increased population doubling rate at later passages. Karyotyping and comparative genomic hybridization analysis revealed that all examined cell lines had cytogenetic aberrations commonly found in glioblastomas, and there were only minor differences between tumor and early and late passages in the same culture. Whole-transcriptome analysis shows that tumors had interindividual differences. Changes in the overall expression patterns through passaging were modest, with a significant change in only 14 genes; the variation among cultures was, however, reduced through passages. The ability to differentiate differed among tumors but was maintained throughout passaging. The cells initiated tumors upon transplantation to immunodeficient mice with differing phenotypes, but a given cell culture maintained tumor phenotype after serial cultivation. The cultures established maintained individual characteristics specific to culture identity. Thus, each cell culture reflects an image of the tumor—or a personalized model—from which it was derived and remains representative after moderate expansion. PMID:20843775

  3. SIRT1 Overexpression Maintains Cell Phenotype and Function of Endothelial Cells Derived from Induced Pluripotent Stem Cells

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    Jiang, Bin; Jen, Michele; Perrin, Louisiane; Wertheim, Jason A.

    2015-01-01

    Endothelial cells (ECs) that are differentiated from induced pluripotent stem cells (iPSCs) can be used in establishing disease models for personalized drug discovery or developing patient-specific vascularized tissues or organoids. However, a number of technical challenges are often associated with iPSC-ECs in culture, including instability of the endothelial phenotype and limited cell proliferative capacity over time. Early senescence is believed to be the primary mechanism underlying these limitations. Sirtuin1 (SIRT1) is an NAD+-dependent deacetylase involved in the regulation of cell senescence, redox state, and inflammatory status. We hypothesize that overexpression of the SIRT1 gene in iPSC-ECs will maintain EC phenotype, function, and proliferative capacity by overcoming early cell senescence. SIRT1 gene was packaged into a lentiviral vector (LV-SIRT1) and transduced into iPSC-ECs at passage 4. Beginning with passage 5, iPSC-ECs exhibited a fibroblast-like morphology, whereas iPSC-ECs overexpressing SIRT1 maintained EC cobblestone morphology. SIRT1 overexpressing iPSC-ECs also exhibited a higher percentage of canonical markers of endothelia (LV-SIRT1 61.8% CD31+ vs. LV-empty 31.7% CD31+, P < 0.001; LV-SIRT1 46.3% CD144+ vs. LV-empty 20.5% CD144+, P < 0.02), with a higher nitric oxide synthesis, lower β-galactosidase production indicating decreased senescence (3.4% for LV-SIRT1 vs. 38.6% for LV-empty, P < 0.001), enhanced angiogenesis, increased deacetylation activity, and higher proliferation rate. SIRT1 overexpressing iPSC-ECs continued to proliferate through passage 9 with high purity of EC-like characteristics, while iPSC-ECs without SIRT1 overexpression became senescent after passage 5. Taken together, SIRT1 overexpression in iPSC-ECs maintains EC phenotype, improves EC function, and extends cell lifespan, overcoming critical hurdles associated with the use of iPSC-ECs in translational research. PMID:26413932

  4. Reprogramming suppresses premature senescence phenotypes of Werner syndrome cells and maintains chromosomal stability over long-term culture.

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    Akira Shimamoto

    Full Text Available Werner syndrome (WS is a premature aging disorder characterized by chromosomal instability and cancer predisposition. Mutations in WRN are responsible for the disease and cause telomere dysfunction, resulting in accelerated aging. Recent studies have revealed that cells from WS patients can be successfully reprogrammed into induced pluripotent stem cells (iPSCs. In the present study, we describe the effects of long-term culture on WS iPSCs, which acquired and maintained infinite proliferative potential for self-renewal over 2 years. After long-term cultures, WS iPSCs exhibited stable undifferentiated states and differentiation capacity, and premature upregulation of senescence-associated genes in WS cells was completely suppressed in WS iPSCs despite WRN deficiency. WS iPSCs also showed recapitulation of the phenotypes during differentiation. Furthermore, karyotype analysis indicated that WS iPSCs were stable, and half of the descendant clones had chromosomal profiles that were similar to those of parental cells. These unexpected properties might be achieved by induced expression of endogenous telomerase gene during reprogramming, which trigger telomerase reactivation leading to suppression of both replicative senescence and telomere dysfunction in WS cells. These findings demonstrated that reprogramming suppressed premature senescence phenotypes in WS cells and WS iPSCs could lead to chromosomal stability over the long term. WS iPSCs will provide opportunities to identify affected lineages in WS and to develop a new strategy for the treatment of WS.

  5. A red wine polyphenolic extract reduces the activation phenotype of cultured human liver myofibroblasts

    Institute of Scientific and Technical Information of China (English)

    Véronique Neaud; Jean Rosenbaum

    2008-01-01

    AIM: To test the effect of a standardized red wine polyphenolic extract (RWPE) on the phenotype of human liver myofibroblasts in culture.METHODS: Human myofibroblasts grown from liver explants were used in this study. Cell proliferation was measured with the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. Signaling events were analyzed by western blot with phosphospecific antibodies. Matrix-metalloproteinase activity was measured with gel zymography.RESULTS: We found that cell proliferation was dosedependently decreased by up to 90% by RWPE while cell viability was not affected. Exposure to RWPE also greatly decreased the phosphorylation of ERK1/ERK2 and Akt in response to stimulation by the mitogenic factor platelet-derived growth factor BB (PDGF-BB).Finally, RWPE affected extracellular matrix remodeling by decreasing the secretion by myofibroblasts of matrixmetalloproteinase-2 and of tissue inhibitor of matrixmetalloproteinases-1.CONCLUSION: Altogether, RWPE decreases the activation state of liver myofibroblasts. The identification of the active compounds in RWPE could offer new therapeutic strategies against liver fibrosis.

  6. Liver transcriptome profile in pigs with extreme phenotypes of intramuscular fatty acid composition

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    Ramayo-Caldas Yuliaxis

    2012-10-01

    Full Text Available Abstract Background New advances in high-throughput technologies have allowed for the massive analysis of genomic data, providing new opportunities for the characterization of the transcriptome architectures. Recent studies in pigs have employed RNA-Seq to explore the transcriptome of different tissues in a reduced number of animals. The main goal of this study was the identification of differentially-expressed genes in the liver of Iberian x Landrace crossbred pigs showing extreme phenotypes for intramuscular fatty acid composition using RNA-Seq. Results The liver transcriptomes of two female groups (H and L with phenotypically extreme intramuscular fatty acid composition were sequenced using RNA-Seq. A total of 146 and 180 unannotated protein-coding genes were identified in intergenic regions for the L and H groups, respectively. In addition, a range of 5.8 to 7.3% of repetitive elements was found, with SINEs being the most abundant elements. The expression in liver of 186 (L and 270 (H lncRNAs was also detected. The higher reproducibility of the RNA-Seq data was validated by RT-qPCR and porcine expression microarrays, therefore showing a strong correlation between RT-qPCR and RNA-Seq data (ranking from 0.79 to 0.96, as well as between microarrays and RNA-Seq (r=0.72. A differential expression analysis between H and L animals identified 55 genes differentially-expressed between groups. Pathways analysis revealed that these genes belong to biological functions, canonical pathways and three gene networks related to lipid and fatty acid metabolism. In concordance with the phenotypic classification, the pathways analysis inferred that linolenic and arachidonic acids metabolism was altered between extreme individuals. In addition, a connection was observed among the top three networks, hence suggesting that these genes are interconnected and play an important role in lipid and fatty acid metabolism. Conclusions In the present study RNA-Seq was used

  7. Peroxiredoxin II Is Essential for Maintaining Stemness by Redox Regulation in Liver Cancer Cells.

    Science.gov (United States)

    Kwon, Taeho; Bak, Yesol; Park, Young-Ho; Jang, Gyu-Beom; Nam, Jeong-Seok; Yoo, Jeong Eun; Park, Young Nyun; Bak, In Seon; Kim, Jin-Man; Yoon, Do-Young; Yu, Dae-Yeul

    2016-05-01

    Redox regulation in cancer stem cells (CSCs) is viewed as a good target for cancer therapy because redox status plays an important role in cancer stem-cell maintenance. Here, we investigated the role of Peroxiredoxin II (Prx II), an antioxidant enzyme, in association with maintenance of liver CSCs. Our study demonstrates that Prx II overexpressed in liver cancer cells has high potential for self-renewal activity. Prx II expression significantly corelated with expression of epithelial-cell adhesion molecules (EpCAM) and cytokerain 19 in liver cancer tissues of hepatocellular carcinoma (HCC) patients. Downregulation of Prx II in Huh7 cells with treatment of siRNA reduced expression of EpCAM and CD133 as well as Sox2 in accordance with increased ROS and apoptosis, which were reversed in Huh7-hPrx II cells. Huh7-hPrx II cells exhibited strong sphere-formation activity compared with mock cells. Vascular endothelial growth factor (VEGF) exposure enhanced sphere formation, cell-surface expression of EpCAM and CD133, and pSTAT3 along with activation of VEGF receptor 2 in Huh7-hPrx II cells. The result also emerged in Huh7-H-ras(G12V) and SK-HEP-1-H-ras(G12V) cells with high-level expression of Prx II. Prx II was involved in regulation of VEGF driving cancer stem cells through VEGFR-2/STAT3 signaling to upregulate Bmi1 and Sox2. In addition, knockdown of Prx II in Huh7-H-ras(G12V) cells showed significant reduction in cell migration in vitro and in tumorigenic potential in vivo. Taken together, all the results demonstrated that Prx II plays a key role in the CSC self-renewal of HCC cells through redox regulation. Stem Cells 2016;34:1188-1197.

  8. A collaborative approach to developing an electronic health record phenotyping algorithm for drug-induced liver injury.

    Science.gov (United States)

    Overby, Casey Lynnette; Pathak, Jyotishman; Gottesman, Omri; Haerian, Krystl; Perotte, Adler; Murphy, Sean; Bruce, Kevin; Johnson, Stephanie; Talwalkar, Jayant; Shen, Yufeng; Ellis, Steve; Kullo, Iftikhar; Chute, Christopher; Friedman, Carol; Bottinger, Erwin; Hripcsak, George; Weng, Chunhua

    2013-12-01

    To describe a collaborative approach for developing an electronic health record (EHR) phenotyping algorithm for drug-induced liver injury (DILI). We analyzed types and causes of differences in DILI case definitions provided by two institutions-Columbia University and Mayo Clinic; harmonized two EHR phenotyping algorithms; and assessed the performance, measured by sensitivity, specificity, positive predictive value, and negative predictive value, of the resulting algorithm at three institutions except that sensitivity was measured only at Columbia University. Although these sites had the same case definition, their phenotyping methods differed by selection of liver injury diagnoses, inclusion of drugs cited in DILI cases, laboratory tests assessed, laboratory thresholds for liver injury, exclusion criteria, and approaches to validating phenotypes. We reached consensus on a DILI phenotyping algorithm and implemented it at three institutions. The algorithm was adapted locally to account for differences in populations and data access. Implementations collectively yielded 117 algorithm-selected cases and 23 confirmed true positive cases. Phenotyping for rare conditions benefits significantly from pooling data across institutions. Despite the heterogeneity of EHRs and varied algorithm implementations, we demonstrated the portability of this algorithm across three institutions. The performance of this algorithm for identifying DILI was comparable with other computerized approaches to identify adverse drug events. Phenotyping algorithms developed for rare and complex conditions are likely to require adaptive implementation at multiple institutions. Better approaches are also needed to share algorithms. Early agreement on goals, data sources, and validation methods may improve the portability of the algorithms.

  9. Human embryonic and induced pluripotent stem cells maintain phenotype but alter their metabolism after exposure to ROCK inhibitor

    Science.gov (United States)

    Vernardis, Spyros I.; Terzoudis, Konstantinos; Panoskaltsis, Nicki; Mantalaris, Athanasios

    2017-01-01

    Human pluripotent stem cells (hPSCs) are adhesion-dependent cells that require cultivation in colonies to maintain growth and pluripotency. Robust differentiation protocols necessitate single cell cultures that are achieved by use of ROCK (Rho kinase) inhibitors. ROCK inhibition enables maintenance of stem cell phenotype; its effects on metabolism are unknown. hPSCs were exposed to 10 μM ROCK inhibitor for varying exposure times. Pluripotency (TRA-1-81, SSEA3, OCT4, NANOG, SOX2) remained unaffected, until after prolonged exposure (96 hrs). Gas chromatography–mass spectrometry metabolomics analysis identified differences between ROCK-treated and untreated cells as early as 12 hrs. Exposure for 48 hours resulted in reduction in glycolysis, glutaminolysis, the citric acid (TCA) cycle as well as the amino acids pools, suggesting the adaptation of the cells to the new culture conditions, which was also reflected by the expression of the metabolic regulators, mTORC1 and tp53 and correlated with cellular proliferation status. While gene expression and protein levels did not reveal any changes in the physiology of the cells, metabolomics revealed the fluctuating state of the metabolism. The above highlight the usefulness of metabolomics in providing accurate and sensitive information on cellular physiological status, which could lead to the development of robust and optimal stem cell bioprocesses. PMID:28165055

  10. Human embryonic and induced pluripotent stem cells maintain phenotype but alter their metabolism after exposure to ROCK inhibitor.

    Science.gov (United States)

    Vernardis, Spyros I; Terzoudis, Konstantinos; Panoskaltsis, Nicki; Mantalaris, Athanasios

    2017-02-06

    Human pluripotent stem cells (hPSCs) are adhesion-dependent cells that require cultivation in colonies to maintain growth and pluripotency. Robust differentiation protocols necessitate single cell cultures that are achieved by use of ROCK (Rho kinase) inhibitors. ROCK inhibition enables maintenance of stem cell phenotype; its effects on metabolism are unknown. hPSCs were exposed to 10 μM ROCK inhibitor for varying exposure times. Pluripotency (TRA-1-81, SSEA3, OCT4, NANOG, SOX2) remained unaffected, until after prolonged exposure (96 hrs). Gas chromatography-mass spectrometry metabolomics analysis identified differences between ROCK-treated and untreated cells as early as 12 hrs. Exposure for 48 hours resulted in reduction in glycolysis, glutaminolysis, the citric acid (TCA) cycle as well as the amino acids pools, suggesting the adaptation of the cells to the new culture conditions, which was also reflected by the expression of the metabolic regulators, mTORC1 and tp53 and correlated with cellular proliferation status. While gene expression and protein levels did not reveal any changes in the physiology of the cells, metabolomics revealed the fluctuating state of the metabolism. The above highlight the usefulness of metabolomics in providing accurate and sensitive information on cellular physiological status, which could lead to the development of robust and optimal stem cell bioprocesses.

  11. Self-renewal and pluripotency is maintained in human embryonic stem cells by co-culture with human fetal liver stromal cells expressing hypoxia inducible factor 1alpha.

    Science.gov (United States)

    Ji, Lei; Liu, Yu-xiao; Yang, Chao; Yue, Wen; Shi, Shuang-shuang; Bai, Ci-xian; Xi, Jia-fei; Nan, Xue; Pei, Xue-Tao

    2009-10-01

    Human embryonic stem (hES) cells are typically maintained on mouse embryonic fibroblast (MEF) feeders or with MEF-conditioned medium. However, these xenosupport systems greatly limit the therapeutic applications of hES cells because of the risk of cross-transfer of animal pathogens. The stem cell niche is a unique tissue microenvironment that regulates the self-renewal and differentiation of stem cells. Recent evidence suggests that stem cells are localized in the microenvironment of low oxygen. We hypothesized that hypoxia could maintain the undifferentiated phenotype of embryonic stem cells. We have co-cultured a human embryonic cell line with human fetal liver stromal cells (hFLSCs) feeder cells stably expressing hypoxia-inducible factor-1 alpha (HIF-1alpha), which is known as the key transcription factor in hypoxia. The results suggested HIF-1alpha was critical for preventing differentiation of hES cells in culture. Consistent with this observation, hypoxia upregulated the expression of Nanog and Oct-4, the key factors expressed in undifferentiated stem cells. We further demonstrated that HIF-1alpha could upregulate the expression of some soluble factors including bFGF and SDF-1alpha, which are released into the microenvironment to maintain the undifferentiated status of hES cells. This suggests that the targets of HIF-1alpha are secreted soluble factors rather than a cell-cell contact mechanism, and defines an important mechanism for the inhibition of hESCs differentiation by hypoxia. Our findings developed a transgene feeder co-culture system and will provide a more reliable alternative for future therapeutic applications of hES cells.

  12. Bone marrow-derived mesenchymal stem cells maintain the resting phenotype of microglia and inhibit microglial activation.

    Directory of Open Access Journals (Sweden)

    Ke Yan

    Full Text Available Many studies have shown that microglia in the activated state may be neurotoxic. It has been proven that uncontrolled or over-activated microglia play an important role in many neurodegenerative disorders. Bone marrow-derived mesenchymal stem cells (BMSCs have been shown in many animal models to have a therapeutic effect on neural damage. Such a therapeutic effect is attributed to the fact that BMSCs have the ability to differentiate into neurons and to produce trophic factors, but there is little information available in the literature concerning whether BMSCs play a therapeutic role by affecting microglial activity. In this study, we triggered an inflammatory response situation in vitro by stimulating microglia with the bacterial endotoxin lipopolysaccharide (LPS, and then culturing these microglia with BMSC-conditioned medium (BMSC-CM. We found that BMSC-CM significantly inhibited proliferation and secretion of pro-inflammatory factors by activated microglia. Furthermore, we found that the phagocytic capacity of microglia was also inhibited by BMSC-CM. Finally, we investigated whether the induction of apoptosis and the production of nitric oxide (NO were involved in the inhibition of microglial activation. We found that BMSC-CM significantly induced apoptosis of microglia, while no apoptosis was apparent in the LPS-stimulated microglia. Our study also provides evidence that NO participates in the inhibitory effect of BMSCs. Our experimental results provide evidence that BMSCs have the ability to maintain the resting phenotype of microglia or to control microglial activation through their production of several factors, indicating that BMSCs could be a promising therapeutic tool for treatment of diseases associated with microglial activation.

  13. Phenotypic and functional analysis of human fetal liver hematopoietic stem cells in culture.

    Science.gov (United States)

    Rollini, Pierre; Faes-Van't Hull, Eveline; Kaiser, Stefan; Kapp, Ursula; Leyvraz, Serge

    2007-04-01

    Steady-state hematopoiesis and hematopoietic transplantation rely on the unique potential of stem cells to undergo both self-renewal and multilineage differentiation. Fetal liver (FL) represents a promising alternative source of hematopoietic stem cells (HSCs), but limited by the total cell number obtained in a typical harvest. We reported that human FL nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulating cells (SRCs) could be expanded under simple stroma-free culture conditions. Here, we sought to further characterize FL HSC/SRCs phenotypically and functionally before and following culture. Unexpanded or cultured FL cell suspensions were separated into various subpopulations. These were tested for long-term culture potential and for in vivo repopulating function following transplantation into NOD/SCID mice. We found that upon culture of human FL cells, a tight association between classical stem cell phenotypes, such as CD34(+) /CD38(-) and/or side population, and NOD/SCID repopulating function was lost, as observed with other sources. Although SRC activity before and following culture consistently correlated with the presence of a CD34(+) cell population, we provide evidence that, contrary to umbilical cord blood and adult sources, stem cells present in both CD34(+) and CD34(-) FL populations can sustain long-term hematopoietic cultures. Furthermore, upon additional culture, CD34-depleted cell suspensions, devoid of SRCs, regenerated a population of CD34(+) cells possessing SRC function. Our studies suggest that compared to neonatal and adult sources, the phenotypical characteristics of putative human FL HSCs may be less strictly defined, and reinforce the accumulated evidence that human FL represents a unique, valuable alternative and highly proliferative source of HSCs for clinical applications.

  14. Von Hippel-Lindau status influences phenotype of liver cancers arising from PTEN loss

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    Sendor AB

    2015-02-01

    Full Text Available Adam B Sendor,1 Kathryn E Hacker,1 Shufen Chen,1 Armando L Corona,1 Oishee Sen,1 Derek Y Chiang,1 Anna Snavely,1 Arlin B Rogers,2 Stephanie A Montgomery,1 W Kimryn Rathmell,1 Autumn J McRee11Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA; 2Section of Pathology, Department of Biomedical Sciences, Cummings School of Veterinary Medicine, Tufts University, Boston, MA, USABackground: PTEN loss contributes to the development of liver diseases including hepatic steatosis and both hepatocellular carcinoma (HCC and cholangiocarcinoma (CC. The factors that influence the penetrance of these conditions are unclear. We explored the influence of sustained hypoxia signaling through co-deletion of Pten and Vhl in a murine model.Methods: We used a CreER-linked Keratin 18 mouse model to conditionally delete Pten, Vhl or both in somatic cells of adult mice, evaluating the resultant tumors by histology and gene expression microarray. Existing sets of gene expression data for human HCC and CC were examined for pathways related to those observed in the murine tumors, and a cohort of human CC samples was evaluated for relationships between HIF-1α expression and clinical outcomes.Results: Both Pten deletion genotypes developed liver tumors, but with differing phenotypes. Pten deletion alone led to large hepatic tumors with widespread hepatosteatosis. Co-deletion of Pten and Vhl with the Keratin 18 promoter resulted in reduced steatosis and a reduced tumor burden that was characterized by a trabecular architecture similar to CC. Genes associated with hepatic steatosis were coordinately expressed in the human HCC dataset, while genes involved in hypoxia response were upregulated in tumors from the human CC dataset. HIF-1α expression and overall survival were examined in an independent cohort of human CC tumors with no statistical differences uncovered.Conclusion: Pten deletion in Keratin 18 expressing cells leads to

  15. Liver-specific disruption of PPARγ in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes

    OpenAIRE

    Matsusue, Kimihiko; Haluzik, Martin; Lambert, Gilles; Yim, Sun-Hee; Gavrilova, Oksana; Ward, Jerrold M.; Brewer, Bryan; Reitman, Marc L.; Gonzalez, Frank J.

    2003-01-01

    To elucidate the function of PPARγ in leptin-deficient mouse (ob/ob) liver, a PPARγ liver-null mouse on an ob/ob background, ob/ob-PPARγ(fl/fl)AlbCre+, was produced using a floxed PPARγ allele, PPARγ(fl/fl), and Cre recombinase under control of the albumin promoter (AlbCre). The liver of ob/ob-PPARγ(fl/fl)AlbCre+ mice had a deletion of exon 2 and a corresponding loss of full-length PPARγ mRNA and protein. The PPARγ-deficient liver in ob/ob mice was smaller and had a dramatically decreased tri...

  16. Optimization of Liver Decellularization Maintains Extracellular Matrix Micro-Architecture and Composition Predisposing to Effective Cell Seeding.

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    Panagiotis Maghsoudlou

    Full Text Available Hepatic tissue engineering using decellularized scaffolds is a potential therapeutic alternative to conventional transplantation. However, scaffolds are usually obtained using decellularization protocols that destroy the extracellular matrix (ECM and hamper clinical translation. We aim to develop a decellularization technique that reliably maintains hepatic microarchitecture and ECM components. Isolated rat livers were decellularized by detergent-enzymatic technique with (EDTA-DET or without EDTA (DET. Histology, DNA quantification and proteomics confirmed decellularization with further DNA reduction with the addition of EDTA. Quantification, histology, immunostaining, and proteomics demonstrated preservation of extracellular matrix components in both scaffolds with a higher amount of collagen and glycosaminoglycans in the EDTA-DET scaffold. Scanning electron microscopy and X-ray phase contrast imaging showed microarchitecture preservation, with EDTA-DET scaffolds more tightly packed. DET scaffold seeding with a hepatocellular cell line demonstrated complete repopulation in 14 days, with cells proliferating at that time. Decellularization using DET preserves microarchitecture and extracellular matrix components whilst allowing for cell growth for up to 14 days. Addition of EDTA creates a denser, more compact matrix. Transplantation of the scaffolds and scaling up of the methodology are the next steps for successful hepatic tissue engineering.

  17. Global liver gene expression differences in Nelore steers with divergent residual feed intake phenotypes.

    Science.gov (United States)

    Tizioto, Polyana C; Coutinho, Luiz L; Decker, Jared E; Schnabel, Robert D; Rosa, Kamila O; Oliveira, Priscila S N; Souza, Marcela M; Mourão, Gerson B; Tullio, Rymer R; Chaves, Amália S; Lanna, Dante P D; Zerlotini-Neto, Adhemar; Mudadu, Mauricio A; Taylor, Jeremy F; Regitano, Luciana C A

    2015-03-25

    Efficiency of feed utilization is important for animal production because it can reduce greenhouse gas emissions and improve industry profitability. However, the genetic basis of feed utilization in livestock remains poorly understood. Recent developments in molecular genetics, such as platforms for genome-wide genotyping and sequencing, provide an opportunity to identify genes and pathways that influence production traits. It is known that transcriptional networks influence feed efficiency-related traits such as growth and energy balance. This study sought to identify differentially expressed genes in animals genetically divergent for Residual Feed Intake (RFI), using RNA sequencing methodology (RNA-seq) to obtain information from genome-wide expression profiles in the liver tissues of Nelore cattle. Differential gene expression analysis between high Residual Feed Intake (HRFI, inefficient) and low Residual Feed Intake (LRFI, efficient) groups was performed to provide insights into the molecular mechanisms that underlie feed efficiency-related traits in beef cattle. A total of 112 annotated genes were identified as being differentially expressed between animals with divergent RFI phenotypes. These genes are involved in ion transport and metal ion binding; act as membrane or transmembrane proteins; and belong to gene clusters that are likely related to the transport and catalysis of molecules through the cell membrane and essential mechanisms of nutrient absorption. Genes with functions in cellular signaling, growth and proliferation, cell death and survival were also differentially expressed. Among the over-represented pathways were drug or xenobiotic metabolism, complement and coagulation cascades, NRF2-mediated oxidative stress, melatonin degradation and glutathione metabolism. Our data provide new insights and perspectives on the genetic basis of feed efficiency in cattle. Some previously identified mechanisms were supported and new pathways controlling feed

  18. BRCA1-IRIS overexpression promotes and maintains the tumor initiating phenotype: implications for triple negative breast cancer early lesions.

    Science.gov (United States)

    Sinha, Abhilasha; Paul, Bibbin T; Sullivan, Lisa M; Sims, Hillary; El Bastawisy, Ahmed; Yousef, Hend F; Zekri, Abdel-Rahman N; Bahnassy, Abeer A; ElShamy, Wael M

    2017-02-07

    Tumor-initiating cells (TICs) are cancer cells endowed with self-renewal, multi-lineage differentiation, increased chemo-resistance, and in breast cancers the CD44+/CD24-/ALDH1+ phenotype. Triple negative breast cancers show lack of BRCA1 expression in addition to enhanced basal, epithelial-to-mesenchymal transition (EMT), and TIC phenotypes. BRCA1-IRIS (hereafter IRIS) is an oncogene produced by the alternative usage of the BRCA1 locus. IRIS is involved in induction of replication, transcription of selected oncogenes, and promoting breast cancer cells aggressiveness. Here, we demonstrate that IRIS overexpression (IRISOE) promotes TNBCs through suppressing BRCA1 expression, enhancing basal-biomarkers, EMT-inducers, and stemness-enforcers expression. IRISOE also activates the TIC phenotype in TNBC cells through elevating CD44 and ALDH1 expression/activity and preventing CD24 surface presentation by activating the internalization pathway EGFR→c-Src→cortactin. We show that the intrinsic sensitivity to an anti-CD24 cross-linking antibody-induced cell death in membranous CD24 expressing/luminal A cells could be acquired in cytoplasmic CD24 expressing IRISOE TNBC/TIC cells through IRIS silencing or inactivation. We show that fewer IRISOE TNBC/TICs cells form large tumors composed of TICs, resembling TNBCs early lesions in patients that contain metastatic precursors capable of disseminating and metastasizing at an early stage of the disease. IRIS-inhibitory peptide killed these IRISOE TNBC/TICs, in vivo and prevented their dissemination and metastasis. We propose IRIS inactivation could be pursued to prevent dissemination and metastasis from early TNBC tumor lesions in patients.

  19. Acid ceramidase maintains the chondrogenic phenotype of expanded primary chondrocytes and improves the chondrogenic differentiation of bone marrow-derived mesenchymal stem cells.

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    Calogera M Simonaro

    Full Text Available Acid ceramidase is required to maintain the metabolic balance of several important bioactive lipids, including ceramide, sphingosine and sphingosine-1-phosphate. Here we show that addition of recombinant acid ceramidase (rAC to primary chondrocyte culture media maintained low levels of ceramide and led to elevated sphingosine by 48 hours. Surprisingly, after three weeks of expansion the chondrogenic phenotype of these cells also was markedly improved, as assessed by a combination of histochemical staining (Alcian Blue and Safranin-O, western blotting (e.g., Sox9, aggrecan, collagen 2A1, and/or qPCR. The same effects were evident in rat, equine and human cells, and were observed in monolayer and 3-D cultures. rAC also reduced the number of apoptotic cells in some culture conditions, contributing to overall improved cell quality. In addition to these effects on primary chondrocytes, when rAC was added to freshly harvested rat, equine or feline bone marrow cultures an ~2-fold enrichment of mesenchymal stem cells (MSCs was observed by one week. rAC also improved the chondrogenic differentiation of MSCs, as revealed by histochemical and immunostaining. These latter effects were synergistic with TGF-beta1. Based on these results we propose that rAC could be used to improve the outcome of cell-based cartilage repair by maintaining the quality of the expanded cells, and also might be useful in vivo to induce endogenous cartilage repair in combination with other techniques. The results also suggest that short-term changes in sphingolipid metabolism may lead to longer-term effects on the chondrogenic phenotype.

  20. The microbiota maintain homeostasis of liver-resident γδT-17 cells in a lipid antigen/CD1d-dependent manner

    Science.gov (United States)

    Li, Fenglei; Hao, Xiaolei; Chen, Yongyan; Bai, Li; Gao, Xiang; Lian, Zhexiong; Wei, Haiming; Sun, Rui; Tian, Zhigang

    2017-01-01

    The microbiota control regional immunity using mechanisms such as inducing IL-17A-producing γδ T (γδT-17) cells in various tissues. However, little is known regarding hepatic γδT cells that are constantly stimulated by gut commensal microbes. Here we show hepatic γδT cells are liver-resident cells and predominant producers of IL-17A. The microbiota sustain hepatic γδT-17 cell homeostasis, including activation, survival and proliferation. The global commensal quantity affects the number of liver-resident γδT-17 cells; indeed, E. coli alone can generate γδT-17 cells in a dose-dependent manner. Liver-resident γδT-17 cell homeostasis depends on hepatocyte-expressed CD1d, that present lipid antigen, but not Toll-like receptors or IL-1/IL-23 receptor signalling. Supplementing mice in vivo or loading hepatocytes in vitro with exogenous commensal lipid antigens augments the hepatic γδT-17 cell number. Moreover, the microbiota accelerate nonalcoholic fatty liver disease through hepatic γδT-17 cells. Thus, our work describes a unique liver-resident γδT-17 cell subset maintained by gut commensal microbes through CD1d/lipid antigens. PMID:28067223

  1. The Relationship between PON1 phenotype and PON1-192 genotype in detoxification of three oxons by human liver.

    Science.gov (United States)

    Mutch, Elaine; Daly, Ann K; Williams, Faith M

    2007-02-01

    Phosphorothioate pesticides (OP) such as diazinon, chlorpyrifos, and parathion are activated to highly toxic oxon metabolites by the cytochromes P450 (P450s), mainly in the liver. Simultaneously, the P450s catalyze detoxification of OP to nontoxic dearylated metabolites. The oxon is then detoxified to the dearylated metabolite by PON1, an A-esterase present in the liver and blood serum. The aims of this study were to define the influence of PON1-192 genotype and phenotype on the capacity of human liver microsomes (n = 27) to detoxify the oxons diazoxon, chlorpyrifos-oxon, and paraoxon. Near physiological assay conditions were used to reflect as closely as possible metabolism in vivo and because the hydrolytic activity of the allelic variants of PON1-192 are differentially affected by a number of conditions. The rates of hydrolysis of diazoxon, chlorpyrifos-oxon, and paraoxon varied 5.7-, 16-, and 56-fold, respectively, regardless of PON1-192 genotype. Individuals with the PON1-192RR genotype preferentially hydrolyzed paraoxon (p < 0.01), and the R allele was associated with higher hydrolytic activity toward chlorpyrifos-oxon, but not diazoxon. There were strongly significant relationships between phenylacetate and paraoxon hydrolysis (p < 0.001) and phenylacetate and chlorpyrifos-oxon hydrolysis (p < 0.001), but not between phenylacetate and diazoxon hydrolysis. These data highlight the importance of PON1 phenotype for efficient hydrolysis of paraoxon and chlorpyrifos-oxon, but environmental and yet unknown genetic factors are more important than PON1-192 genotype in determining capacity to hydrolyze diazoxon.

  2. Phenotyping the effect of diet on non-alcoholic fatty liver disease

    NARCIS (Netherlands)

    Wit, de N.J.W.; Afman, L.A.; Mensink, M.R.; Muller, M.R.

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is associated with the growing incidence of metabolic syndrome. Diet is an important contributor to the pathogenesis of NAFLD. In this review, we focused on recent publications reporting on the effect of macro- and micronutrients on development and progressi

  3. Dual Function of Glucosamine in Gelatin/Hyaluronic Acid Cryogel to Modulate Scaffold Mechanical Properties and to Maintain Chondrogenic Phenotype for Cartilage Tissue Engineering.

    Science.gov (United States)

    Chen, Chih-Hao; Kuo, Chang-Yi; Wang, Yan-Jie; Chen, Jyh-Ping

    2016-11-23

    Glucosamine (GlcN) fulfills many of the requirements as an ideal component in scaffolds used in cartilage tissue engineering. The incorporation of GlcN in a gelatin/hyaluronic acid (GH) cryogel scaffold could provide biological cues in maintaining the phenotype of chondrocytes. Nonetheless, substituting gelatin with GlcN may also decrease the crosslinking density and modulate the mechanical properties of the cryogel scaffold, which may be beneficial as physical cues for chondrocytes in the scaffold. Thus, we prepared cryogel scaffolds containing 9% GlcN (GH-GlcN9) and 16% GlcN (GH-GlcN16) by carbodiimide-mediated crosslinking reactions at -16 °C. The crosslinking density and the mechanical properties of the cryogel matrix could be tuned by adjusting the content of GlcN used during cryogel preparation. In general, incorporation of GlcN did not influence scaffold pore size and ultimate compressive strain but increased porosity. The GH-GlcN16 cryogel showed the highest swelling ratio and degradation rate in hyaluronidase and collagenase solutions. On the contrary, the Young's modulus, storage modulus, ultimate compressive stress, energy dissipation level, and rate of stress relaxation decreased by increasing the GlcN content in the cryogel. The release of GlcN from the scaffolds in the culture medium of chondrocytes could be sustained for 21 days for GH-GlcN16 in contrast to only 7 days for GH-GlcN9. In vitro cell culture experiments using rabbit articular chondrocytes revealed that GlcN incorporation affected cell proliferation, morphology, and maintenance of chondrogenic phenotype. Overall, GH-GlcN16 showed the best performance in maintaining chondrogenic phenotype with reduced cell proliferation rate but enhanced glycosaminoglycans (GAGs) and type II collagen (COL II) secretion. Quantitative real-time polymerase chain reaction also showed time-dependent up-regulation of cartilage-specific marker genes (COL II, aggrecan and Sox9) for GH-GlcN16. Implantation of

  4. Dual Function of Glucosamine in Gelatin/Hyaluronic Acid Cryogel to Modulate Scaffold Mechanical Properties and to Maintain Chondrogenic Phenotype for Cartilage Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Chih-Hao Chen

    2016-11-01

    Full Text Available Glucosamine (GlcN fulfills many of the requirements as an ideal component in scaffolds used in cartilage tissue engineering. The incorporation of GlcN in a gelatin/hyaluronic acid (GH cryogel scaffold could provide biological cues in maintaining the phenotype of chondrocytes. Nonetheless, substituting gelatin with GlcN may also decrease the crosslinking density and modulate the mechanical properties of the cryogel scaffold, which may be beneficial as physical cues for chondrocytes in the scaffold. Thus, we prepared cryogel scaffolds containing 9% GlcN (GH-GlcN9 and 16% GlcN (GH-GlcN16 by carbodiimide-mediated crosslinking reactions at −16 °C. The crosslinking density and the mechanical properties of the cryogel matrix could be tuned by adjusting the content of GlcN used during cryogel preparation. In general, incorporation of GlcN did not influence scaffold pore size and ultimate compressive strain but increased porosity. The GH-GlcN16 cryogel showed the highest swelling ratio and degradation rate in hyaluronidase and collagenase solutions. On the contrary, the Young’s modulus, storage modulus, ultimate compressive stress, energy dissipation level, and rate of stress relaxation decreased by increasing the GlcN content in the cryogel. The release of GlcN from the scaffolds in the culture medium of chondrocytes could be sustained for 21 days for GH-GlcN16 in contrast to only 7 days for GH-GlcN9. In vitro cell culture experiments using rabbit articular chondrocytes revealed that GlcN incorporation affected cell proliferation, morphology, and maintenance of chondrogenic phenotype. Overall, GH-GlcN16 showed the best performance in maintaining chondrogenic phenotype with reduced cell proliferation rate but enhanced glycosaminoglycans (GAGs and type II collagen (COL II secretion. Quantitative real-time polymerase chain reaction also showed time-dependent up-regulation of cartilage-specific marker genes (COL II, aggrecan and Sox9 for GH-GlcN16

  5. C/EBP maintains chromatin accessibility in liver and facilitates glucocorticoid receptor recruitment to steroid response elements

    DEFF Research Database (Denmark)

    Grøntved, Lars; John, Sam; Baek, Songjoon

    2013-01-01

    Mechanisms regulating transcription factor interaction with chromatin in intact mammalian tissues are poorly understood. Exploiting an adrenalectomized mouse model with depleted endogenous glucocorticoids, we monitor changes of the chromatin landscape in intact liver tissue following glucocorticoid...... injection. Upon activation of the glucocorticoid receptor (GR), proximal regions of activated and repressed genes are remodelled, and these remodelling events correlate with RNA polymerase II occupancy of regulated genes. GR is exclusively associated with accessible chromatin and 62% percent of GR...... remodelling specifically at sites co-occupied by GR and C/EBPβ. Collectively, we demonstrate a highly cooperative mechanism by which C/EBPβ regulates selective GR binding to the genome in liver tissue. We suggest that selective targeting of GR in other tissues is likely mediated by the combined action of cell...

  6. Carcinogenic Liver Fluke Secretes Extracellular Vesicles That Promote Cholangiocytes to Adopt a Tumorigenic Phenotype

    OpenAIRE

    2015-01-01

    This is the final version. It was first published by OUP at http://dx.doi.org/10.1093/infdis/jiv291 Background.  Throughout Asia there is an unprecedented link between cholangiocarcinoma and infection with the liver fluke Opisthorchis viverrini. Multiple processes including chronic inflammation and secretion of parasite proteins into the biliary epithelium drive infection towards cancer. Until now, the mechanism and effects of parasite protein entry into cholangiocytes was unknown. ...

  7. Chemical inhibitors of CYP450 enzymes in liver microsomes: combining selectivity and unbound fractions to guide selection of appropriate concentration in phenotyping assays.

    Science.gov (United States)

    Nirogi, Ramakrishna; Palacharla, Raghava Choudary; Uthukam, Venkatesham; Manoharan, Arunkumar; Srikakolapu, Surya Rao; Kalaikadhiban, Ilayaraja; Boggavarapu, Rajesh Kumar; Ponnamaneni, Ranjith Kumar; Ajjala, Devender Reddy; Bhyrapuneni, Gopinadh

    2015-02-01

    1. Chemical inhibition is the widely used method in reaction phenotyping assays for estimation of specific enzyme contribution to a given metabolic pathway. The results from phenotyping assays depend on the selectivity of chemical inhibitor and the concentration of inhibitor used in the incubation. 2. The higher protein concentrations used in the in vitro phenotyping assays will impact the inhibitory potency of chemical inhibitors. The objective of the study is to evaluate comprehensively the selectivity of chemical inhibitors and to guide in selecting appropriate concentration of the chemical inhibitors to be used in the phenotyping assays based on unbound fractions. 3. Selectivity of chemical inhibitors against nine major CYP450 isoforms was determined in liver microsomes using standard probe substrates. The unbound fractions of the selective inhibitors were determined in human liver microsomes using high-throughput equilibrium dialysis. Combining unbound inhibitor concentrations that are required to inhibit the CYP450 activities by 90% and unbound fractions of the chemical inhibitors in liver microsomes appropriate total concentrations of the inhibitors to be used in the phenotyping assays were reported. 4. The findings suggest that non-specific binding of the chemical inhibitors need to be taken into account while selecting concentrations for phenotyping assays.

  8. Activation of Constitutive Androstane Receptor (CAR) in Mice Results in Maintained Biliary Excretion of Bile Acids Despite a Marked Decrease of Bile Acids in Liver.

    Science.gov (United States)

    Lickteig, Andrew J; Csanaky, Iván L; Pratt-Hyatt, Matthew; Klaassen, Curtis D

    2016-06-01

    Activation of Constitutive Androstane Receptor (CAR) protects against bile acid (BA)-induced liver injury. This study was performed to determine the effect of CAR activation on bile flow, BA profile, as well as expression of BA synthesis and transport genes. Synthetic CAR ligand 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) was administered to mice for 4 days. BAs were quantified by UPLC-MS/MS (ultraperformance liquid chromatography-tandem mass spectrometry). CAR activation decreases total BAs in livers of male (49%) and female mice (26%), largely attributable to decreases of the 12α-hydroxylated BA taurocholic acid (T-CA) (males (M) 65%, females (F) 45%). Bile flow in both sexes was increased by CAR activation, and the increases were BA-independent. CAR activation did not alter biliary excretion of total BAs, but overall BA composition changed. Excretion of muricholic (6-hydroxylated) BAs was increased in males (101%), and the 12α-OH proportion of biliary BAs was decreased in both males (37%) and females (28%). The decrease of T-CA in livers of males and females correlates with the decreased mRNA of the sterol 12α-hydroxylase Cyp8b1 in males (71%) and females (54%). As a response to restore BAs to physiologic concentrations in liver, mRNA of Cyp7a1 is upregulated following TCPOBOP (males 185%, females 132%). In ilea, mRNA of the negative feedback regulator Fgf15 was unaltered by CAR activation, indicating biliary BA excretion was sufficient to maintain concentrations of total BAs in the small intestine. In summary, the effects of CAR activation on BAs in male and female mice are quite similar, with a marked decrease in the major BA T-CA in the liver.

  9. Prevention of the disrupted enamel phenotype in Slc4a4-null mice using explant organ culture maintained in a living host kidney capsule.

    Directory of Open Access Journals (Sweden)

    Xin Wen

    Full Text Available Slc4a4-null mice are a model of proximal renal tubular acidosis (pRTA. Slc4a4 encodes the electrogenic sodium base transporter NBCe1 that is involved in transcellular base transport and pH regulation during amelogenesis. Patients with mutations in the SLC4A4 gene and Slc4a4-null mice present with dysplastic enamel, amongst other pathologies. Loss of NBCe1 function leads to local abnormalities in enamel matrix pH regulation. Loss of NBCe1 function also results in systemic acidemic blood pH. Whether local changes in enamel pH and/or a decrease in systemic pH are the cause of the abnormal enamel phenotype is currently unknown. In the present study we addressed this question by explanting fetal wild-type and Slc4a4-null mandibles into healthy host kidney capsules to study enamel formation in the absence of systemic acidemia. Mandibular E11.5 explants from NBCe1-/- mice, maintained in host kidney capsules for 70 days, resulted in teeth with enamel and dentin with morphological and mineralization properties similar to cultured NBCe1+/+ mandibles grown under identical conditions. Ameloblasts express a number of proteins involved in dynamic changes in H+/base transport during amelogenesis. Despite the capacity of ameloblasts to dynamically modulate the local pH of the enamel matrix, at least in the NBCe1-/- mice, the systemic pH also appears to contribute to the enamel phenotype. Extrapolating these data to humans, our findings suggest that in patients with NBCe1 mutations, correction of the systemic metabolic acidosis at a sufficiently early time point may lead to amelioration of enamel abnormalities.

  10. Limbal Fibroblasts Maintain Normal Phenotype in 3D RAFT Tissue Equivalents Suggesting Potential for Safe Clinical Use in Treatment of Ocular Surface Failure.

    Science.gov (United States)

    Massie, Isobel; Dale, Sarah B; Daniels, Julie T

    2015-06-01

    Limbal epithelial stem cell deficiency can cause blindness, but transplantation of these cells on a carrier such as human amniotic membrane can restore vision. Unfortunately, clinical graft manufacture using amnion can be inconsistent. Therefore, we have developed an alternative substrate, Real Architecture for 3D Tissue (RAFT), which supports human limbal epithelial cells (hLE) expansion. Epithelial organization is improved when human limbal fibroblasts (hLF) are incorporated into RAFT tissue equivalent (TE). However, hLF have the potential to transdifferentiate into a pro-scarring cell type, which would be incompatible with therapeutic transplantation. The aim of this work was to assess the scarring phenotype of hLF in RAFT TEs in hLE+ and hLE- RAFT TEs and in nonairlifted and airlifted RAFT TEs. Diseased fibroblasts (dFib) isolated from the fibrotic conjunctivae of ocular mucous membrane pemphigoid (Oc-MMP) patients were used as a pro-scarring positive control against which hLF were compared using surrogate scarring parameters: matrix metalloproteinase (MMP) activity, de novo collagen synthesis, α-smooth muscle actin (α-SMA) expression, and transforming growth factor-β (TGF-β) secretion. Normal hLF and dFib maintained different phenotypes in RAFT TE. MMP-2 and -9 activity, de novo collagen synthesis, and α-SMA expression were all increased in dFib cf. normal hLF RAFT TEs, although TGF-β1 secretion did not differ between normal hLF and dFib RAFT TEs. Normal hLF do not progress toward a scarring-like phenotype during culture in RAFT TEs and, therefore, may be safe to include in therapeutic RAFT TE, where they can support hLE, although in vivo work is required to confirm this. dFib RAFT TEs (used in this study as a positive control) may be useful toward the development of an ex vivo disease model of Oc-MMP.

  11. The organoid-initiating cells in mouse pancreas and liver are phenotypically and functionally similar

    Directory of Open Access Journals (Sweden)

    Craig Dorrell

    2014-09-01

    Full Text Available Pancreatic Lgr5 expression has been associated with organoid-forming epithelial progenitor populations but the identity of the organoid-initiating epithelial cell subpopulation has remained elusive. Injury causes the emergence of an Lgr5+ organoid-forming epithelial progenitor population in the adult mouse liver and pancreas. Here, we define the origin of organoid-initiating cells from mouse pancreas and liver prior to Lgr5 activation. This clonogenic population was defined as MIC1-1C3+/CD133+/CD26− in both tissues and the frequency of organoid initiation within this population was approximately 5% in each case. The transcriptomes of these populations overlapped extensively and showed enrichment of epithelial progenitor-associated regulatory genes such as Sox9 and FoxJ1. Surprisingly, pancreatic organoid cells also had the capacity to generate hepatocyte-like cells upon transplantation to Fah−/− mice, indicating a differentiation capacity similar to hepatic organoids. Although spontaneous endocrine differentiation of pancreatic progenitors was not observed in culture, adenoviral delivery of fate-specifying factors Pdx1, Neurog3 and MafA induced insulin expression without glucagon or somatostatin. Pancreatic organoid cultures therefore preserve many key attributes of progenitor cells while allowing unlimited expansion, facilitating the study of fate determination.

  12. Immunohistochemical phenotyping of the inflammatory infiltrate in de novo autoimmune hepatitis after liver transplantation in children.

    Science.gov (United States)

    Hadžić, Nedim; Quaglia, Alberto; Cotoi, Corina; Hussain, Munther J; Brown, Nigel; Vergani, Diego; Mieli-Vergani, Giorgina

    2012-08-01

    We have investigated the inflammatory infiltrate in post-transplant dn-AIH, a form of late insidious graft rejection, focusing on transcription factors defining effector and T-regs, using an antigen retrieval immunohistochemical method on archived liver tissue, and compared it with ACR and classical AIH. Paraffin-embedded liver biopsies from pediatric patients with dn-AIH (n = 10), ACR (n = 10), and AIH (n = 13) were selected randomly and stained using antibodies directed to CD4, CD8, T-bet (marker of Th1 polarization), GATA-3 (marker of Th2 polarization), FOXP3 (marker for T regulatory cells), IL-17, CD56 (NK cells), and perforin. Portal and lobular lymphocytic infiltrate was assessed semi-quantitatively. Prominent CD4, CD8, and T-bet positivity were present in both the lobular and portal infiltrate of all three conditions. Overall T-bet score of lobular inflammation in the dn-AIH group was lower than in the ACR and AIH groups (p = 0.02). In contrast, most samples showed absent or minimal GATA-3 positivity. FOXP3, CD56, IL-17, and perforin staining of mild to moderate severity were present in all three groups in both the portal and lobular infiltrate. A Th1 polarization of the inflammatory infiltrate characterizes dn-AIH, but also ACR and AIH.

  13. Troglitazone thiol adduct formation in human liver microsomes: enzyme kinetics and reaction phenotyping.

    Science.gov (United States)

    Gan, Jinping; Qu, Qinling; He, Bing; Shyu, Wen C; Rodrigues, A David; He, Kan

    2008-08-01

    Troglitazone (TGZ) induced hepatotoxicity has been linked to cytochrome P450 (CYP)-catalyzed reactive metabolite formation. Therefore, the kinetics and CYP specificity of reactive metabolite formation were studied using dansyl glutathione (dGSH) as a trapping agent after incubation of TGZ with human liver microsomes (HLM) and recombinant human CYP proteins. CYP2C8 exhibited the highest rate of TGZ adduct (TGZ-dGS) formation, followed by CYP3A4, CYP3A5, and CYP2C19. The involvement of CYP2C8 and CYP3A4 was confirmed with CYP form-selective chemical inhibitors. The impact of TGZ concentration on the rate of TGZ-dGS formation was also evaluated. In this instance, two distinctly different profiles were observed with recombinant CYP3A4 and CYP2C8. It is concluded that both CYP3A4/5 and CYP2C8 play a major role in the formation of TGZ adduct in HLM. However, the contribution of these CYPs varies depending on their relative expression and the concentration of TGZ.

  14. Advanced aging phenotype is revealed by epigenetic modifications in rat liver after in utero malnutrition.

    Science.gov (United States)

    Heo, Hye J; Tozour, Jessica N; Delahaye, Fabien; Zhao, Yongmei; Cui, Lingguang; Barzilai, Nir; Einstein, Francine Hughes

    2016-10-01

    Adverse environmental exposures of mothers during fetal period predispose offspring to a range of age-related diseases earlier in life. Here, we set to determine whether a deregulated epigenetic pattern is similar in young animals whose mothers' nutrition was modulated during fetal growth to that acquired during normal aging in animals. Using a rodent model of maternal undernutrition (UN) or overnutrition (ON), we examined cytosine methylation profiles of liver from young female offspring and compared them to age-matched young controls and aged (20-month-old) animals. HELP-tagging, a genomewide restriction enzyme and sequencing assay demonstrates that fetal exposure to two different maternal diets is associated with nonrandom dysregulation of methylation levels with profiles similar to those seen in normal aging animals and occur in regions mapped to genes relevant to metabolic diseases and aging. Functional consequences were assessed by gene expression at 9 weeks old with more significant changes at 6 months of age. Early developmental exposures to unfavorable maternal diets result in altered methylation profiles and transcriptional dysregulation in Prkcb, Pc, Ncor2, and Smad3 that is also seen with normal aging. These Notch pathway and lipogenesis genes may be useful for prediction of later susceptibility to chronic disease.

  15. Adoptive transfer of heme oxygenase-1 (HO-1)-modified macrophages rescues the nuclear factor erythroid 2-related factor (Nrf2) antiinflammatory phenotype in liver ischemia/reperfusion injury.

    Science.gov (United States)

    Huang, Jing; Shen, Xiu-Da; Yue, Shi; Zhu, Jianjun; Gao, Feng; Zhai, Yuan; Busuttil, Ronald W; Ke, Bibo; Kupiec-Weglinski, Jerzy W

    2014-10-14

    Macrophages are instrumental in the pathophysiology of liver ischemia/reperfusion injury (IRI). Although Nrf2 regulates macrophage-specific heme oxygenase-1 (HO-1) antioxidant defense, it remains unknown whether HO-1 induction might rescue macrophage Nrf2-dependent antiinflammatory functions. This study explores the mechanisms by which the Nrf2-HO-1 axis regulates sterile hepatic inflammation responses after adoptive transfer of ex vivo modified HO-1 overexpressing bone marrow-derived macrophages (BMMs). Livers in Nrf2-deficient mice preconditioned with Ad-HO-1 BMMs, but not Ad-β-Gal-BMMs, ameliorated liver IRI (at 6 h of reperfusion after 90 min of warm ischemia), evidenced by improved hepatocellular function (serum alanine aminotransferase [sALT] levels) and preserved hepatic architecture (Suzuki histological score). Treatment with Ad-HO-1 BMMs decreased neutrophil accumulation, proinflammatory mediators and hepatocellular necrosis/apoptosis in ischemic livers. Moreover, Ad-HO-1 transfection of Nrf2-deficient BMMs suppressed M1 (Nos2(+)) while promoting the M2 (Mrc-1/Arg-1(+)) phenotype. Unlike in controls, Ad-HO-1 BMMs increased the expression of Notch1, Hes1, phosphorylation of Stat3 and Akt in IR-stressed Nrf2-deficient livers as well as in lipopolysaccharide (LPS)-stimulated BMMs. Thus, adoptive transfer of ex vivo generated Ad-HO-1 BMMs rescued Nrf2-dependent antiinflammatory phenotype by promoting Notch1/Hes1/Stat3 signaling and reprogramming macrophages toward the M2 phenotype. These findings provide the rationale for a novel clinically attractive strategy to manage IR liver inflammation/damage.

  16. Early gestational gene transfer with targeted ATP7B expression in the liver improves phenotype in a murine model of Wilson's disease.

    Science.gov (United States)

    Roybal, J L; Endo, M; Radu, A; Gray, L; Todorow, C A; Zoltick, P W; Lutsenko, S; Flake, A W

    2012-11-01

    The ideal gene therapy for metabolical liver disorders would target hepatocytes before the onset of disease and be durable, non-toxic and non-immunogenic. Early gestational gene transfer can achieve such goals. Here, we demonstrate that prenatal gene transfer of human Atp7b reduces liver pathology and improves biochemical markers in Atp7b(-/-) mice, a murine model of Wilson's disease (WD). Following prenatal injection of lentivirus vector containing the human Atp7b gene under the transcriptional control of a liver-specific promoter, the full-length ATP7B was detectable in mouse livers for the entire duration of experiments (20 weeks after birth). In contrast to a marked pathology in non-injected animals, livers from age-matched treated mice consistently demonstrated normal gross and histological morphology. Hepatic copper content was decreased in the majority of treated mice, although remaining copper levels varied. Improvement of hepatic copper metabolism was further apparent from the presence of copper-bound ceruloplasmin in the sera and normalization of the mRNA levels for HMG CoA-reductase. With this approach, the complete loss of copper transport function can be ameliorated, as evident from phenotypical improvement in treated Atp7b(-/-) mice. This study provides proof of principle for in utero gene therapy in WD and other liver-based enzyme deficiencies.

  17. An In Vitro Procedure for Phenotypic Screening of Growth Parameters and Symbiotic Performances in Lotus corniculatus Cultivars Maintained in Different Nutritional Conditions

    Directory of Open Access Journals (Sweden)

    Vladimir Totev Valkov

    2016-10-01

    Full Text Available The establishment of legumes crops with phenotypic traits that favour their persistence and competitiveness in mixed swards is a pressing task in sustainable agriculture. However, to fully exploit the potential benefits of introducing pasture-based grass-legume systems, an increased scientific knowledge of legume agronomy for screening of favourable traits is needed. We exploited a short-cut phenotypic screening as a preliminary step to characterize the growth capacity of three different Lotus corniculatus cvs cultivated in different nutritional conditions as well as the evaluation of their nodulation capacities. This experimental scheme, developed for legume species amenable to grow on agar plates conditions, may represent a very preliminary step to achieve phenotypic discrimination on different cultivars.

  18. An In Vitro Procedure for Phenotypic Screening of Growth Parameters and Symbiotic Performances in Lotus corniculatus Cultivars Maintained in Different Nutritional Conditions.

    Science.gov (United States)

    Valkov, Vladimir Totev; Chiurazzi, Maurizio

    2016-10-13

    The establishment of legumes crops with phenotypic traits that favour their persistence and competitiveness in mixed swards is a pressing task in sustainable agriculture. However, to fully exploit the potential benefits of introducing pasture-based grass-legume systems, an increased scientific knowledge of legume agronomy for screening of favourable traits is needed. We exploited a short-cut phenotypic screening as a preliminary step to characterize the growth capacity of three different Lotus corniculatus cvs cultivated in different nutritional conditions as well as the evaluation of their nodulation capacities. This experimental scheme, developed for legume species amenable to grow on agar plates conditions, may represent a very preliminary step to achieve phenotypic discrimination on different cultivars.

  19. An In Vitro Procedure for Phenotypic Screening of Growth Parameters and Symbiotic Performances in Lotus corniculatus Cultivars Maintained in Different Nutritional Conditions

    Science.gov (United States)

    Valkov, Vladimir Totev; Chiurazzi, Maurizio

    2016-01-01

    The establishment of legumes crops with phenotypic traits that favour their persistence and competitiveness in mixed swards is a pressing task in sustainable agriculture. However, to fully exploit the potential benefits of introducing pasture-based grass-legume systems, an increased scientific knowledge of legume agronomy for screening of favourable traits is needed. We exploited a short-cut phenotypic screening as a preliminary step to characterize the growth capacity of three different Lotus corniculatus cvs cultivated in different nutritional conditions as well as the evaluation of their nodulation capacities. This experimental scheme, developed for legume species amenable to grow on agar plates conditions, may represent a very preliminary step to achieve phenotypic discrimination on different cultivars. PMID:27754365

  20. Thrombopoietin induced proliferation and differentiation of fetal liver CD34+ cells with phenotype change from hemopoiesis to neurogenesis

    Institute of Scientific and Technical Information of China (English)

    Ning Ma; Dongchu Ma; Yi Tao; Yinghui Sun; Di Lin; Huiying Yu; Jinlong Jian; Wei Jia; Boquan Jin

    2008-01-01

    BACKGROUND: Previous studies have reported a neurotrophin-like motif in the N-terminal receptor binding region of the thrombopoietin (TPO) molecule, and have described localization of TPO and TPO receptor in the brain. Therefore, it is believed that TPO may be involved in regulation of neurogenesis.OBJECTIVE: To validate the effect of TPO on trans-differentiation, or differentiation from hematopoietic stem cells (HSCs) to neural stem cells (NSCs).DESIGN, TIME AND SETTING: Comparative studies were performed from March 2004 to April 2007 at the Department of Experimental Medicine, Northern Hospital, and the Department of Immunology, Fourth Military Medical University of Chinese PLA.MATERIALS: Human fetal liver (FL) was obtained from fetuses after water-balloon abortion. Gestational age ranged from 16 to 20 weeks. The study was approved by the Institutional Review Board and Ethics Committee of the Northern Hospital. TPO was kindly provided by Genentech Inc (USA). Iscove's Modified Dulbecco's Medium (IMDM) and neurobasal(tm) medium were purchased from Invitrogen (USA). MACS CD34 multisort kit was purchased from Miltenyi Biotec (Germany). METHODS: CD34+ cells were isolated from human FL mononuclear cells using MACS CD34 multisort kit and cultured at 1 × 105/mL in IMDM, containing TPO for 60 days with weekly changes of half of the medium. After culturing for 30 and 60 days, the TPO-induced cells were resuspended in neurobasal(tm) medium containing 10% fetal brain extracts and plated in an 8-well BIOCOAT(R) poly-D-Lysine Culture Slide and cultured for another 7 days. MAIN OUTCOME MEASURES: Cell number, viability, phenotype and expression of hemopoiesis-related and neurogenesis-related proteins were examined by trypan blue exclusion with hemocytometer, immunoblot, immunocytochemistry and flow cytometry.RESULTS: After 60 days of induction with TPO, the cell number increased by 4.6-fold compared to the initial culture. Although the proportion of the cells expressing the

  1. Umbilical cord tissue-derived mesenchymal stem cells grow best under GMP-compliant culture conditions and maintain their phenotypic and functional properties.

    Science.gov (United States)

    Hartmann, Isabel; Hollweck, Trixi; Haffner, Silvia; Krebs, Michaela; Meiser, Bruno; Reichart, Bruno; Eissner, Günther

    2010-12-15

    Mesenchymal stem cells (MSCs) are fibroblast-like multipotent stem cells that can differentiate into cell types of mesenchymal origin. Because of their immune properties and differentiation, potential MSCs are discussed for the use in tissue regeneration and tolerance induction in transplant medicine. This cell type can easily be obtained from the umbilical cord tissue (UCMSC) without medical intervention. Standard culture conditions include fetal bovine serum (FBS) which may not be approved for clinical settings. Here, we analyzed the phenotypic and functional properties of UCMSC under xeno-free (XF, containing GMP-certified human serum) and serum-free (SF) culture conditions in comparison with standard UCMSC cultures. Phenotypically, UCMSC showed no differences in the expression of mesenchymal markers or differentiation capacity. Functionally, XF and SF-cultured UCMSC have comparable adipogenic, osteogenic, and endothelial differentiation potential. Interestingly, the UCMSC-mediated suppression of T cell proliferation in an allogeneic mixed lymphocyte reaction (MLR) is more effective in XF and SF media than in standard FBS-containing cultures. Regarding the mechanism of action of MLR suppression, transwell experiments revealed that in neither UCMSC culture a direct cell-cell contact is necessary for inhibiting T cell proliferation, and that the major effector molecule is prostaglandin E₂ (PGE₂). Taken together, GMP-compliant growth media qualify for long-term cultures of UCMSC which is important for a future clinical study design in regenerative and transplant medicine. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. Utility of intersystem extrapolation factors in early reaction phenotyping and the quantitative extrapolation of human liver microsomal intrinsic clearance using recombinant cytochromes P450.

    Science.gov (United States)

    Chen, Yuan; Liu, Liling; Nguyen, Khanh; Fretland, Adrian J

    2011-03-01

    Reaction phenotyping using recombinant human cytochromes P450 (P450) has great utility in early discovery. However, to fully realize the advantages of using recombinant expressed P450s, the extrapolation of data from recombinant systems to human liver microsomes (HLM) is required. In this study, intersystem extrapolation factors (ISEFs) were established for CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 using 11 probe substrates, based on substrate depletion and/or metabolite formation kinetics. The ISEF values for CYP2C9, CYP2D6, and CYP3A4 determined using multiple substrates were similar across substrates. When enzyme kinetics of metabolite formation for CYP1A2, 2C9, 2D6, and 3A4 were used, the ISEFs determined were generally within 2-fold of that determined on the basis of substrate depletion. Validation of ISEFs was conducted using 10 marketed drugs by comparing the extrapolated data with published data. The major isoforms responsible for the metabolism were identified, and the contribution of the predominant P450s was similar to that of previously reported data. In addition, phenotyping data from internal compounds, extrapolated using the rhP450-ISEF method, were comparable to those obtained using an HLM-based inhibition assay approach. Moreover, the intrinsic clearance (CL(int)) calculated from extrapolated rhP450 data correlated well with measured HLM CL(int). The ISEF method established in our laboratory provides a convenient tool in early reaction phenotyping for situations in which the HLM-based inhibition approach is limited by low turnover and/or unavailable metabolite formation. Furthermore, this method allows for quantitative extrapolation of HLM intrinsic clearance from rhP450 phenotyping data simultaneously to obtaining the participating metabolizing enzymes.

  3. Characterization of niflumic acid as a selective inhibitor of human liver microsomal UDP-glucuronosyltransferase 1A9: application to the reaction phenotyping of acetaminophen glucuronidation.

    Science.gov (United States)

    Miners, John O; Bowalgaha, Kushari; Elliot, David J; Baranczewski, Pawel; Knights, Kathleen M

    2011-04-01

    Enzyme selective inhibitors represent the most valuable experimental tool for reaction phenotyping. However, only a limited number of UDP-glucuronosyltransferase (UGT) enzyme-selective inhibitors have been identified to date. This study characterized the UGT enzyme selectivity of niflumic acid (NFA). It was demonstrated that 2.5 μM NFA is a highly selective inhibitor of recombinant and human liver microsomal UGT1A9 activity. Higher NFA concentrations (50-100 μM) inhibited UGT1A1 and UGT2B15 but had little effect on the activities of UGT1A3, UGT1A4, UGT1A6, UGT2B4, UGT2B7, and UGT2B17. NFA inhibited 4-methylumbelliferone and propofol (PRO) glucuronidation by recombinant UGT1A9 and PRO glucuronidation by human liver microsomes (HLM) according to a mixed (competitive-noncompetitive) mechanism, with K(i) values ranging from 0.10 to 0.40 μM. Likewise, NFA was a mixed or noncompetitive inhibitor of recombinant and human liver microsomal UGT1A1 (K(i) range 14-18 μM), whereas competitive inhibition (K(i) 62 μM) was observed with UGT2B15. NFA was subsequently applied to the reaction phenotyping of human liver microsomal acetaminophen (APAP) glucuronidation. Consistent with previous reports, APAP was glucuronidated by recombinant UGT1A1, UGT1A6, UGT1A9, and UGT2B15. NFA concentrations in the range of 2.5 to 100 μM inhibited APAP glucuronidation by UGT1A1, UGT1A9, and UGT2B15 but not by UGT1A6. The mean V(max) for APAP glucuronidation by HLM was reduced by 20, 35, and 40%, respectively, in the presence of 2.5, 50, and 100 μM NFA. Mean K(m) values decreased in parallel with V(max), although the magnitude of the decrease was smaller. Taken together, the NFA inhibition data suggest that UGT1A6 is the major enzyme involved in APAP glucuronidation.

  4. Phenotyping and auto-antibody production by liver-infiltrating B cells in primary sclerosing cholangitis and primary biliary cholangitis.

    Science.gov (United States)

    Chung, Brian K; Guevel, Bardia T; Reynolds, Gary M; Gupta Udatha, D B R K; Henriksen, Eva Kristine Klemsdal; Stamataki, Zania; Hirschfield, Gideon M; Karlsen, Tom Hemming; Liaskou, Evaggelia

    2017-02-01

    Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are immune-mediated biliary diseases that demonstrate prominent and restricted genetic association with human leukocyte antigen (HLA) alleles. In PBC, anti-mitochondrial antibodies (AMA) are specific and used as diagnostic biomarkers. PSC-relevant auto-antibodies remain controversial despite a distinct HLA association that mirrors archetypical auto-antigen driven disorders. Herein, we compared antibody-secreting B cells (ASCs) in PSC and PBC liver explants to determine if liver-infiltrating ASCs represent an opportune and novel source of disease-relevant auto-antibodies. Using enzymatic digestion and mechanical disruption, liver mononuclear cells (LIMCs) were isolated from fresh PSC and PBC explants and plasmablast (CD19+CD27+CD38(hi)CD138-) and plasma cell (CD19+CD27+CD38(hi)CD138+) ASCs were enumerated by flow cytometry. We observed 45-fold fewer plasma cells in PSC explants (n = 9) compared to PBC samples (n = 5, p < 0.01) and 10-fold fewer IgA-, IgG- and IgM-positive ASCs (p < 0.05). Liver-infiltrating ASCs from PSC and PBC explants were functional and produced similar concentrations of IgA, IgG and IgM following 2 weeks of culture. Antibody production by PBC ASCs (n = 3) was disease-specific as AMA to pyruvate dehydrogenase complex E2 subunit (PDC-E2) was detected by immunostaining, immunoblotting and ELISA. Antibody profiling of PSC supernatants (n = 9) using full-length recombinant human protein arrays (Cambridge Protein Arrays) revealed reactivities to nucleolar protein 3 (5/9) and hematopoietic cell-specific Lyn substrate 1 (3/9). Array analysis of PBC supernatants (n = 3) detected reactivities to PDC-E2 and hexokinase 1 (3/3). In conclusion, we detected unique frequencies of liver-infiltrating ASCs in PSC and PBC and in so doing, highlight a feasible approach for understanding disease-relevant antibodies in PSC. Copyright © 2016. Published by Elsevier Ltd.

  5. Angiogenically stimulated alternative monocytes maintain their pro-angiogenic and non-inflammatory phenotype in long-term co-cultures with HUVEC.

    Science.gov (United States)

    Krüger, Anne; Mayer, Anke; Roch, Toralf; Schulz, Christian; Lendlein, Andreas; Jung, Friedrich

    2014-01-01

    Angiogenically stimulated alternative monocytes (aMO2) could be established as cellular release system accelerating the endothelialization of polymers rendering their surfaces hemocompatibility in a short-term study. However, for their clinical application it is essential that aMO2 do not switch back to the MO1 state sustaining their capability as cellular release system over an extended period of time. We explored whether aMO2 can maintain their differentiation state over 21 days in a mono- and in a co-culture with HUVEC. In comparison, the influence of recombinant VEGF-A165 on the endothelialization of biomaterials was assessed including endothelial cell (HUVEC) density, organisation of the endothelial cytoskeleton, cytokine secretion profile and release of prostacyclin, thromboxane A2 and matrix metalloproteinases. In mono-culture aMO2 secreted high amounts of VEGF and other growth factors/cytokines. Co-cultured with HUVEC, aMO2 accelerated the formation of a confluent HUVEC monolayer. Furthermore, no pro-inflammatory cytokines were found, neither in aMO2-mono, nor in co-cultures with HUVEC indicating that the majority of the aMO2 remained stable in their aMO2 state during the 21 days of cultivation. In contrast, the addition of recombinant VEGF-A165 instead of the co-culture with aMO2 resulted in the formation of stress fibres, dissociated marginal filament bands, and a detachment of HUVEC. In addition, the profile of bioactive agents of HUVEC (e.g. prostacyclin, thromboxane A2, matrix metalloproteinases, IFN-γ and TNF-α) was influenced by the VEGF-A165 treatment inducing the detachment of HUVEC. In conclusion, in co-culture with HUVEC aMO2 remained stable in their type 2 state over 21 days confirming the suitability of aMO2 as biological release system for the endothelialization of biomaterial surfaces with constant release of angiogenic factors but without secretion of pro-inflammatory cytokines over three weeks. Therefore, this endothelialization approach

  6. Immunohistochemical expression of mismatch repair genes: A screening tool for predicting mutator phenotype in liver fluke infection-associated intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Upama Liengswangwong; Anant Karalak; Yukio Morishita; Masayuki Noguchi; Thiravud Khuhaprema; Petcharin Srivatanakul; Masanao Miwa

    2006-01-01

    AIM: To clarify possible contributions of DNA mismatch repair (MMR) system in carcinogenesis of liver fluke infection-associated intrahepatic cholangiocarcinoma (ICC) by using immunohistochemical assay.METHODS: A total of 29 ICC samples, which had been assessed for genomic instability by a PCR-based method, were used for study. They were examined immunohistochemically to demonstrate protein expression of two MMR genes, hMSH2 and hMLH1.Results obtained were compared with their mutator phenotype assessed previously.RESULTS: Either hMSH2or hMLH1 protein was obviously expressed in 28 of 29 (96.6%) ICC samples.Positive nuclear localization of hMSH2 or hMLH1 protein was observed in 86.2% (25/29) or 93.1% (27/29) ICC cases, respectively, while their negative nuclear reactivity was only detected in 13.8% (4/29) or 6.9% (2/29) ICC cases analyzed, respectively.CONCLUSION: Our study, probably for the first time,showed through immunohistochemical detection of hMSH2 and hMLH1 gene that DNA MMR system does not play a prominent role in liver fluke infection-associated cholangiocarcinogenesis. These results confirm previous findings on mutational status of these genes assessed through a PCR-based method. The immunohistochemical analysis has proven to be an effective and sensitive approach for screening MMR deficiency regardless of somatic inactivation or promoter hypermethylation of hMSH2 and/or hMLH1 gene. Furthermore,immunohistochemistry is more advantageous compared to mutator phenotyping assay in terms of simplicity,less time consuming and cost effectiveness for screening possible involvements of target MMR genes in tumorigenesis.

  7. Biochemical and phenotypic characterization of human basophilic cells derived from dispersed fetal liver with murine T cell factors

    Energy Technology Data Exchange (ETDEWEB)

    Seldin, D.C.; Caulfield, J.P.; Hein, A.; Osathanondh, R.; Nabel, G.; Schlossman, S.F.; Stevens, R.L.; Austen, K.F.

    1986-03-15

    Metachromatically granulated cells were generated from human fetal liver stem cells cultured in heterologous mouse conditioned medium rich in interleukin 3. After 2 to 3 wk of culture with biweekly changes of medium and selection of nonadherent cells, all cells present in five cultures had cytoplasmic granules. Ultrastructurally, many granules contained fibrillar material or electron-dense cores with fibrils and vesicular fragments. In addition, the granules of many cells were filled with electron-dense material, which in some cases had a fine structure consisting of concentric whorls or a reticular pattern. Analysis of high-affinity IgE receptors on the cultured cells by flow cytometry demonstrated a unimodel fluorescence pattern, suggesting that most cells were in the basophil or mast cell lineage. The cells contained 52 ng/10/sup 6/ cells of histamine and incorporated (/sup 35/S)sulfate at an average rate of 31,300 cpm/10/sup 6/ cells/4 hr into 175,000 m.w. chondroitin sulfate A proteoglycans. Upon activation with 1 ..mu..M calcium ionophore A23187, the cultured cells released 53% of their cell-associated histamine and metabolized arachidonic acid to 15.0 ng/10/sup 6/ cells of immunoreactive leukotriene C/sub 4/ equivalents, 0.5 ng/10/sup 6/ cells of leukotriene B/sub 4/, and 3.1 ng/10/sup 6/ cells of prostaglandin D/sub 2/ (means, n = 3). Thus, stem cells present in human fetal liver give rise, as do stem cells in mouse fetal liver, to metachromatically granulated cells when cultured in the presence of mouse interleukin 3.

  8. Metabolic phenotype and adipose and liver features in a high-fat Western diet-induced mouse model of obesity-linked NAFLD.

    Science.gov (United States)

    Luo, Yuwen; Burrington, Christine M; Graff, Emily C; Zhang, Jian; Judd, Robert L; Suksaranjit, Promporn; Kaewpoowat, Quanhathai; Davenport, Samantha K; O'Neill, Ann Marie; Greene, Michael W

    2016-03-15

    nonalcoholic fatty liver disease (NAFLD), an obesity and insulin resistance associated clinical condition - ranges from simple steatosis to nonalcoholic steatohepatitis. To model the human condition, a high-fat Western diet that includes liquid sugar consumption has been used in mice. Even though liver pathophysiology has been well characterized in the model, little is known about the metabolic phenotype (e.g., energy expenditure, activity, or food intake). Furthermore, whether the consumption of liquid sugar exacerbates the development of glucose intolerance, insulin resistance, and adipose tissue dysfunction in the model is currently in question. In our study, a high-fat Western diet (HFWD) with liquid sugar [fructose and sucrose (F/S)] induced acute hyperphagia above that observed in HFWD-fed mice, yet without changes in energy expenditure. Liquid sugar (F/S) exacerbated HFWD-induced glucose intolerance and insulin resistance and impaired the storage capacity of epididymal white adipose tissue (eWAT). Hepatic TG, plasma alanine aminotransferase, and normalized liver weight were significantly increased only in HFWD+F/S-fed mice. HFWD+F/S also resulted in increased hepatic fibrosis and elevated collagen 1a2, collagen 3a1, and TGFβ gene expression. Furthermore, HWFD+F/S-fed mice developed more profound eWAT inflammation characterized by adipocyte hypertrophy, macrophage infiltration, a dramatic increase in crown-like structures, and upregulated proinflammatory gene expression. An early hypoxia response in the eWAT led to reduced vascularization and increased fibrosis gene expression in the HFWD+F/S-fed mice. Our results demonstrate that sugary water consumption induces acute hyperphagia, limits adipose tissue expansion, and exacerbates glucose intolerance and insulin resistance, which are associated with NAFLD progression.

  9. Eplerenone ameliorates the phenotypes of metabolic syndrome with NASH in liver-specific SREBP-1c Tg mice fed high-fat and high-fructose diet.

    Science.gov (United States)

    Wada, Tsutomu; Miyashita, Yusuke; Sasaki, Motohiro; Aruga, Yusuke; Nakamura, Yuto; Ishii, Yoko; Sasahara, Masakiyo; Kanasaki, Keizo; Kitada, Munehiro; Koya, Daisuke; Shimano, Hitoshi; Tsuneki, Hiroshi; Sasaoka, Toshiyasu

    2013-12-01

    Because the renin-angiotensin-aldosterone system has been implicated in the development of insulin resistance and promotion of fibrosis in some tissues, such as the vasculature, we examined the effect of eplerenone, a selective mineralocorticoid receptor (MR) antagonist, on nonalcoholic steatohepatitis (NASH) and metabolic phenotypes in a mouse model reflecting metabolic syndrome in humans. We adopted liver-specific transgenic (Tg) mice overexpressing the active form of sterol response element binding protein-1c (SREBP-1c) fed a high-fat and fructose diet (HFFD) as the animal model in the present study. When wild-type (WT) C57BL/6 and liver-specific SREBP-1c Tg mice grew while being fed HFFD for 12 wk, body weight and epididymal fat weight increased in both groups with an elevation in blood pressure and dyslipidemia. Glucose intolerance and insulin resistance were also observed. Adipose tissue hypertrophy and macrophage infiltration with crown-like structure formation were also noted in mice fed HFFD. Interestingly, the changes noted in both genotypes fed HFFD were significantly ameliorated with eplerenone. HFFD-fed Tg mice exhibited the histological features of NASH in the liver, including macrovesicular steatosis and fibrosis, whereas HFFD-fed WT mice had hepatic steatosis without apparent fibrotic changes. Eplerenone effectively ameliorated these histological abnormalities. Moreover, the direct suppressive effects of eplerenone on lipopolysaccharide-induced TNFα production in the presence and absence of aldosterone were observed in primary-cultured Kupffer cells and bone marrow-derived macrophages. These results indicated that eplerenone prevented the development of NASH and metabolic abnormalities in mice by inhibiting inflammatory responses in both Kupffer cells and macrophages.

  10. Liver fluke (Fasciola hepatica) naturally infecting introduced European brown hare (Lepus europaeus) in northern Patagonia: phenotype, prevalence and potential risk.

    Science.gov (United States)

    Cuervo, Pablo F; Cataldo, Sophia Di; Fantozzi, M Cecilia; Deis, Erika; Isenrath, Gabriela Diaz; Viberti, Gabriela; Artigas, Patricio; Peixoto, Raquel; Valero, M Adela; Sierra, Roberto Mera Y; Mas-Coma, Santiago

    2015-09-01

    Fascioliasis has recently been included in the WHO list of Neglected Zoonotic Diseases. Besides being a major veterinary health problem, fascioliasis has large underdeveloping effects on the human communities affected. Though scarcely considered in fascioliasis epidemiology, it is well recognized that both native and introduced wildlife species may play a significant role as reservoirs of the disease. The objectives are to study the morphological characteristics of Fasciola hepatica adults and eggs in a population of Lepus europaeus, to assess liver fluke prevalence, and to analyze the potential reservoir role of the European brown hare in northern Patagonia, Argentina, where fascioliasis is endemic. Measures of F. hepatica found in L. europaeus from northern Patagonia demonstrate that the liver fluke is able to fully develop in wild hares and to shed normal eggs through their faeces. Egg shedding to the environment is close to the lower limit obtained for pigs, a domestic animal whose epidemiological importance in endemic areas has already been highlighted. The former, combined with the high prevalence found (14.28%), suggest an even more important role in the transmission cycle than previously considered. The results obtained do not only remark the extraordinary plasticity and adaptability of this trematode species to different host species, but also highlight the role of the European brown hare, and other NIS, as reservoirs capable for parasite spillback to domestic and native cycle, representing a potentially important, but hitherto neglected, cause of disease emergence.

  11. Fasciola hepatica phenotypic characterization in Andean human endemic areas: valley versus altiplanic patterns analysed in liver flukes from sheep from Cajamarca and Mantaro, Peru.

    Science.gov (United States)

    Valero, M Adela; Perez-Crespo, Ignácio; Khoubbane, Messaoud; Artigas, Patricio; Panova, Miroslava; Ortiz, Pedro; Maco, Vicente; Espinoza, José R; Mas-Coma, Santiago

    2012-03-01

    Fascioliasis is a zoonotic parasitic disease caused by Fasciola hepatica and Fasciola gigantica. Of both species, F. hepatica is the only one described in the Americas, mainly transmitted by lymnaeid snail vectors of the Galba/Fossaria group. Human fascioliasis endemic areas are mainly located in high altitude areas of Andean countries. Given the necessity to characterize F. hepatica populations involved, the phenotypic features of fasciolid adults infecting sheep present in human fascioliasis endemic areas were analysed in the Cajamarca Valley and Mantaro Valley (valley transmission patterns) and the northern Bolivian Altiplano (altiplanic transmission pattern). A computer image analysis system (CIAS) was applied on the basis of standardized measurements. The aforementioned highland populations were compared to standard lowland natural and experimental populations of European origin. Liver fluke size was studied by multivariate analyses. Two phenotypic patterns could be distinguished in F. hepatica adult size: the valley pattern (Cajamarca and Mantaro, Peru) and the altiplanic pattern (northern Altiplano, Bolivia). Results showed that the Andean valley population and European standard populations presented a phenotypic homogeneity. The Altiplano population showed a large size range with a pronouncedly lower minimum size indicating that uterus gravidity is reached at a smaller size than in valley populations. The results of this study demonstrate that there is no apparent relationship between the shape of fasciolid adults with regard to altitudinal difference or geographical origin and that allometry-free shape appears as a more stable trait than size in fasciolid species. Results are analysed in terms of intensity/crowding effect aspects and permanent/seasonal transmission characteristics.

  12. The insulin resistance phenotype (muscle or liver) interacts with the type of diet to determine changes in disposition index after 2 years of intervention: the CORDIOPREV-DIAB randomised clinical trial

    NARCIS (Netherlands)

    Blanco-Rojo, R.; Alcala-Diaz, J.F.; Wopereis, S.; Perez-Martinez, P.; Quintana-Navarro, G.M.; Marin, C.; Ordovas, J.M.; Ommen, B. van; Perez-Jimenez, F.; Delgado-Lista, J.; Lopez-Miranda, J.

    2016-01-01

    Aims/hypothesis: The aim of the study was to determine whether basal insulin resistance (IR) phenotype (muscle and/or liver) determines the effect of long-term consumption of a Mediterranean diet or a low-fat diet on tissue-specific IR and beta cell function. Methods: The study was performed in 642

  13. Indazole-based liver X receptor (LXR) modulators with maintained atherosclerotic lesion reduction activity but diminished stimulation of hepatic triglyceride synthesis.

    Science.gov (United States)

    Wrobel, Jay; Steffan, Robert; Bowen, S Marc; Magolda, Ronald; Matelan, Edward; Unwalla, Rayomand; Basso, Michael; Clerin, Valerie; Gardell, Stephen J; Nambi, Ponnal; Quinet, Elaine; Reminick, Jason I; Vlasuk, George P; Wang, Shuguang; Feingold, Irene; Huselton, Christine; Bonn, Tomas; Farnegardh, Mathias; Hansson, Tomas; Nilsson, Annika Goos; Wilhelmsson, Anna; Zamaratski, Edouard; Evans, Mark J

    2008-11-27

    A series of substituted 2-benzyl-3-aryl-7-trifluoromethylindazoles were prepared as LXR modulators. These compounds were partial agonists in transactivation assays when compared to 1 (T0901317) and were slightly weaker with respect to potency and efficacy on LXRalpha than on LXRbeta. Lead compounds in this series 12 (WAY-252623) and 13 (WAY-214950) showed less lipid accumulation in HepG2 cells than potent full agonists 1 and 3 (WAY-254011) but were comparable in efficacy to 1 and 3 with respect to cholesterol efflux in THP-1 foam cells, albeit weaker in potency. Compound 13 reduced aortic lesion area in LDLR knockout mice equivalently to 3 or positive control 2 (GW3965). In a 7-day hamster model, compound 13 showed a lesser propensity for plasma TG elevation than 3, when the compounds were compared at doses in which they elevated ABCA1 and ABCG1 gene expression in duodenum and liver at equal levels. In contrast to results previously published for 2, the lack of TG effect of 13 correlated with its inability to increase liver fatty acid synthase (FAS) gene expression, which was up-regulated 4-fold by 3. These results suggest indazoles such as 13 may have an improved profile for potential use as a therapeutic agent.

  14. Activation of c-Met and upregulation of CD44 expression are associated with the metastatic phenotype in the colorectal cancer liver metastasis model.

    Directory of Open Access Journals (Sweden)

    Victoria A Elliott

    Full Text Available BACKGROUND: Liver metastasis is the most common cause of death in patients with colorectal cancer. Despite extensive research into the biology of cancer progression, the molecular mechanisms that drive colorectal cancer metastasis are not well characterized. METHODS: HT29 LM1, HT29 LM2, HT29 LM3 cell lines were derived from the human colorectal cancer cell line HT29 following multiple rounds of in vivo selection in immunodeficient mice. RESULTS: CD44 expression, a transmembrane glycoprotein involved in cell-cell and cell-matrix adhesions, and cancer cells adhesion to endothelial cells was increased in all in vivo selected cell lines, with maximum CD44 expression and cancer cells adhesion to endothelial cells in the highly metastatic HT29 LM3 cell line. Activation of c-Met upon hepatocyte growth factor (HGF stimulation in the in vivo selected cell lines is CD44 independent. In vitro separation of CD44 high and low expression cells from HT29 LM3 cell line with FACS sorting confirmed that c-Met activation is CD44 independent upon hepatocyte growth factor stimulation. Furthermore, in vivo evaluation of CD44 low and high expressing HT29 LM3 cells demonstrated no difference in liver metastasis penetrance. CONCLUSIONS: Taken together, our findings indicate that the aggressive metastatic phenotype of in vivo selected cell lines is associated with overexpression of CD44 and activation of c-MET. We demonstrate that c-Met activation is CD44 independent upon hepatocyte growth factor stimulation and confirm that CD44 expression in HT29 LM3 cell line is not responsible for the increase in metastatic penetrance in HT29 LM3 cell line.

  15. Caracterização fenotípica e molecular de esporos de fungos micorrízicos arbusculares mantidos em banco de germoplasma Phenotypic and molecular characterization of arbuscular mycorrhizal fungal spores from cultures maintained in germplasm collection

    Directory of Open Access Journals (Sweden)

    Cândido Barreto de Novais

    2010-08-01

    Full Text Available O objetivo deste trabalho foi caracterizar fenotípica e genotipicamente isolados de espécies de fungos micorrízicos arbusculares (FMA mantidos em cultura pura e avaliar a aplicabilidade da técnica PCR-DGGE desenvolvida para Gigaspora, na identificação molecular de espécies de FMA pertencentes a outros gêneros. A caracterização fenotípica das espécies foi realizada de acordo com critérios morfológicos, descritos pela taxonomia, e com uso de descrições originais das espécies presentes na literatura especializada. A análise genotípica foi feita com base na discriminação específica da região V9 do 18S rDNA, que permitiu a diferenciação das espécies e não revelou qualquer diferença entre os isolados geográficos de Glomus clarum, e entre os de Glomus etunicatum. Isto indica a aplicabilidade da técnica para a avaliação da pureza genética e discriminação de espécies de FMA.The objective of this work was to characterize phenotypically and genotypically isolates of arbuscular mycorrhizal fungi (AMF maintained in pure culture and to evaluate the applicability of PCR-DGGE analysis, developed for Gigaspora, for molecular identification of AMF species belonging to other genres. The species phenotypic characterization was done according to morphological criteria, as described by taxonomy, and according to original descriptions of species published in the specialized literature. The genotypic analysis was made through specific discrimination of the V9 region in the 18S rDNA, which allowed the distinction of species and showed no difference among geographical isolates of Glomus clarum, and among those of Glomus etunicatum. This indicates the applicability of this technique for assessment of genetic purity and discrimination of AMF species.

  16. Phenotypes and clinical significance of circulating CD4+CD25+ regulatory T cells (Tregs in patients with acute-on-chronic liver failure (ACLF

    Directory of Open Access Journals (Sweden)

    Yang Jiezuan

    2012-09-01

    Full Text Available Abstract Background CD4+CD25+ regulatory T cells (Tregs play an important role in maintaining immunological tolerance to self and foreign antigens. T cell receptors (TCR reflect the composition and function of T cells. It is not universally agreed that there is a relationship between CD4+CD25+ Treg frequency and the severity of acute-on-chronic liver failure (ACLF. The repertoire of TCR beta chain variable (TCRBV regions of peripheral Tregs in ACLF patients is not well understood. Methods Human PBMCs were separated and sorted into CD4+CD25+ Treg subsets using density gradient centrifugation and magnetic activated cell sorting (MACS. The CD4+CD25high Treg frequency in peripheral blood of ACLF and chronic hepatitis B (CHB patients was measured by flow cytometry. The molecular profiles of TCRBV CDR3 were determined using gene melting spectral pattern (GMSP analysis. TCRBV gene families were cloned and sequenced when the GMSP profiles showed a single-peak. Results CD4+CD25high Treg prevalence in peripheral blood of ACLF patients is increased significantly compared to healthy donors (HDs (P P +CD25high Tregs in ACLF or CHB patients is positively correlated with HBV DNA load. The TCRBV11, BV13.1, BV18, BV20 are the most prevalent TCRBV in CD4+CD25+ Tregs in ACLF and CHB patients. In addition, the CDR3 motifs were relatively conserved in these four TCRBV gene families. Conclusions The CD4+CD25high Tregs prevalence in peripheral blood is indicative of disease severity in ACLF or CHB patients. The relatively conserved TCRBV20 CDR3 motif “TGTGHSPLH” and TCRBV11 CDR3 motif “VYNEQ” may be used in helping diagnosis and treat patients with ACLF.

  17. Determining the association between adipokine expression in multiple tissues and phenotypic features of non-alcoholic fatty liver disease in obesity

    NARCIS (Netherlands)

    Wolfs, M. G. M.; Gruben, N.; Rensen, S. S.; Verdam, F. J.; Greve, J. W.; Driessen, A.; Wijmenga, C.; Buurman, W. A.; Franke, L.; Scheja, L.; Koonen, D. P. Y.; Shiri-Sverdlov, R.; van Haeften, T. W.; Hofker, M. H.; Fu, J.

    2015-01-01

    OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is an obesity-associated disease, and in obesity adipokines are believed to be involved in the development of NAFLD. However, it is still not clear whether adipokines in the liver and/or adipose tissues can be related to the development of specif

  18. Antioxidants in liver health

    Institute of Scientific and Technical Information of China (English)

    Sael; Casas-Grajales; Pablo; Muriel

    2015-01-01

    Liver diseases are a worldwide medical problem because the liver is the principal detoxifying organ and maintains metabolic homeostasis. The liver metabolizes various compounds that produce free radicals(FR).However, antioxidants scavenge FR and maintain the oxidative/antioxidative balance in the liver. When the liver oxidative/antioxidative balance is disrupted, the state is termed oxidative stress. Oxidative stress leadsto deleterious processes in the liver and produces liver diseases. Therefore, restoring antioxidants is essential to maintain homeostasis. One method of restoring antioxidants is to consume natural compounds with antioxidant capacity. The objective of this review is to provide information pertaining to various antioxidants found in food that have demonstrated utility in improving liver diseases.

  19. Increasing Cycles of Intermittent Ischemia Can Effectively Maintain Liver Function during the Acute Phase of Ischemia Reperfusion Injury by Promotion of Bile Flow and Reduction in Bile Salt Toxicity

    NARCIS (Netherlands)

    Peters, J.; Nieuwenhuijs, V. B.; Morphett, A.; Porte, R. J.; Padbury, R. T. A.; Barritt, G. J.

    2009-01-01

    Background/Aims: Intermittent ischemia (INT) can improve liver function following inflow occlusion. The aim was to test whether the number of cycles of INT can be increased without impairing liver function. Methods: Liver function in the acute phase of ischemia reperfusion injury was assessed by mea

  20. Liver transplant

    Science.gov (United States)

    Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...

  1. Acute liver failure

    DEFF Research Database (Denmark)

    Bernal, William; Lee, William M; Wendon, Julia

    2015-01-01

    Over the last three decades acute liver failure (ALF) has been transformed from a rare and poorly understood condition with a near universally fatal outcome, to one with a well characterized phenotype and disease course. Complex critical care protocols are now applied and emergency liver...

  2. Reduced insulin clearance and lower insulin-degrading enzyme expression in the liver might contribute to the thrifty phenotype of protein-restricted mice.

    Science.gov (United States)

    Rezende, Luiz F; Camargo, Rafael L; Branco, Renato C S; Cappelli, Ana P G; Boschero, Antonio C; Carneiro, Everardo M

    2014-09-28

    Nutrient restriction during the early stages of life usually leads to alterations in glucose homeostasis, mainly insulin secretion and sensitivity, increasing the risk of metabolic disorders in adulthood. Despite growing evidence regarding the importance of insulin clearance during glucose homeostasis in health and disease, no information exists about this process in malnourished animals. Thus, in the present study, we aimed to determine the effect of a nutrient-restricted diet on insulin clearance using a model in which 30-d-old C57BL/6 mice were exposed to a protein-restricted diet for 14 weeks. After this period, we evaluated many metabolic variables and extracted pancreatic islet, liver, gastrocnemius muscle (GCK) and white adipose tissue samples from the control (normal-protein diet) and restricted (low-protein diet, LP) mice. Insulin concentrations were determined using RIA and protein expression and phosphorylation by Western blot analysis. The LP mice exhibited lower body weight, glycaemia, and insulinaemia, increased glucose tolerance and altered insulin dynamics after the glucose challenge. The improved glucose tolerance could partially be explained by an increase in insulin sensitivity through the phosphorylation of the insulin receptor/protein kinase B and AMP-activated protein kinase/acetyl-CoA carboxylase in the liver, whereas the changes in insulin dynamics could be attributed to reduced insulin secretion coupled with reduced insulin clearance and lower insulin-degrading enzyme (IDE) expression in the liver and GCK. In summary, protein-restricted mice not only produce and secrete less insulin, but also remove and degrade less insulin. This phenomenon has the double benefit of sparing insulin while prolonging and potentiating its effects, probably due to the lower expression of IDE in the liver, possibly with long-term consequences.

  3. The insulin resistance phenotype (muscle or liver) interacts with the type of diet to determine changes in disposition index after 2 years of intervention: the CORDIOPREV-DIAB randomised clinical trial.

    Science.gov (United States)

    Blanco-Rojo, Ruth; Alcala-Diaz, Juan F; Wopereis, Suzan; Perez-Martinez, Pablo; Quintana-Navarro, Gracia M; Marin, Carmen; Ordovas, Jose M; van Ommen, Ben; Perez-Jimenez, Francisco; Delgado-Lista, Javier; Lopez-Miranda, Jose

    2015-10-16

    The aim of the study was to determine whether basal insulin resistance (IR) phenotype (muscle and/or liver) determines the effect of long-term consumption of a Mediterranean diet or a low-fat diet on tissue-specific IR and beta cell function. The study was performed in 642 patients included in The effect of an olive oil rich Mediterranean diet on type 2 diabetes mellitus risk and incidence study (CORDIOPREV-DIAB). A total of 327 patients were randomised to a Mediterranean diet (35% fat; 22% from monounsaturated fatty acids) and 315 to a low-fat diet (Economia y Competitividad (AGL2012/39615) and by the Ministerio de Ciencia e Innovacion (PIE14/00005 and PI13/00023).

  4. The long-term outcome of patients with polycystic liver disease treated with lanreotide.

    Science.gov (United States)

    Chrispijn, M; Nevens, F; Gevers, T J G; Vanslembrouck, R; van Oijen, M G H; Coudyzer, W; Hoffmann, A L; Dekker, H M; de Man, R A; van Keimpema, L; Drenth, J P H

    2012-01-01

    Polycystic liver disease (PLD) is a phenotypical expression of autosomal dominant polycystic kidney disease and isolated polycystic liver disease. Somatostatin analogues, such as lanreotide, reduce polycystic liver volume. To establish long-term outcome and safety of lanreotide. This was an open-label, observational extension study of a 6-month, randomised, placebo-controlled trial with lanreotide (120 mg/month) in PLD. The length of total treatment was 12 months. Primary endpoint was relative change in liver volume, as determined by CT-volumetry after 12 months of treatment. We offered patients a CT scan 6 months after stopping lanreotide. A total of 41/54 (76%) patients participated in the extension study. Liver volume decreased by 4% (IQR -8% to -1%) after 12 months of treatment. The greatest effect was observed during the first 6 months of treatment (decrease of 4% (IQR -6% to -1%)). Liver volume remained unchanged during the following 6 months. We found that liver volume increased by 4% (IQR 0-6%) 6 months after end of treatment (n = 22). Lanreotide reduces liver volume within the first 6 months of treatment and the beneficial effect is maintained in the following 6 months. Stopping results in recurrence of polycystic liver growth. This suggests that continuous use of lanreotide is needed to maintain its effect. © 2011 Blackwell Publishing Ltd.

  5. Necrotizing Liver Granuloma/Abscess and Constrictive Aspergillosis Pericarditis with Central Nervous System Involvement: Different Remarkable Phenotypes in Different Chronic Granulomatous Disease Genotypes

    Directory of Open Access Journals (Sweden)

    Sanem Eren Akarcan

    2017-01-01

    Full Text Available Chronic granulomatous disease (CGD is a primary immune deficiency causing predisposition to infections with specific microorganisms, Aspergillus species and Staphylococcus aureus being the most common ones. A 16-year-old boy with a mutation in CYBB gene coding gp91phox protein (X-linked disease developed a liver abscess due to Staphylococcus aureus. In addition to medical therapy, surgical treatment was necessary for the management of the disease. A 30-month-old girl with an autosomal recessive form of chronic granulomatous disease (CYBA gene mutation affecting p22phox protein had invasive aspergillosis causing pericarditis, pulmonary abscess, and central nervous system involvement. The devastating course of disease regardless of the mutation emphasizes the importance of early diagnosis and intervention of hematopoietic stem cell transplantation as soon as possible in children with CGD.

  6. Stiffness of hyaluronic acid gels containing liver extracellular matrix supports human hepatocyte function and alters cell morphology.

    Science.gov (United States)

    Deegan, Daniel B; Zimmerman, Cynthia; Skardal, Aleksander; Atala, Anthony; Shupe, Thomas D

    2015-03-01

    Tissue engineering and cell based liver therapies have utilized primary hepatocytes with limited success due to the failure of hepatocytes to maintain their phenotype in vitro. In order to overcome this challenge, hyaluronic acid (HA) cell culture substrates were formulated to closely mimic the composition and stiffness of the normal liver cellular microenvironment. The stiffness of the substrate was modulated by adjusting HA hydrogel crosslinking. Additionally, the repertoire of bioactive molecules within the HA substrate was bolstered by supplementation with normal liver extracellular matrix (ECM). Primary human hepatocyte viability and phenotype were determined over a narrow physiologically relevant range of substrate stiffnesses from 600 to 4600Pa in both the presence and absence of liver ECM. Cell attachment, viability, and organization of the actin cytoskeleton improved with increased stiffness up to 4600Pa. These differences were not evident in earlier time points or substrates containing only HA. However, gene expression for the hepatocyte markers hepatocyte nuclear factor 4 alpha (HNF4α) and albumin significantly decreased on the 4600Pa stiffness at day 7 indicating that cells may not have maintained their phenotype long-term at this stiffness. Function, as measured by albumin secretion, varied with both stiffness and time in culture and peaked at day 7 at the 1200Pa stiffness, slightly below the stiffness of normal liver ECM at 3000Pa. Overall, gel stiffness affected primary human hepatocyte cell adhesion, functional marker expression, and morphological characteristics dependent on both the presence of liver ECM in gel substrates and time in culture.

  7. Alcoholic liver disease: The gut microbiome and liver crosstalk

    OpenAIRE

    Hartmann, Phillipp; Seebauer, Caroline T.; Schnabl, Bernd

    2015-01-01

    Alcoholic liver disease is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with alcoholic liver disease have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing ...

  8. The study of kupffer cells phenotypic changes in alcoholic fatty liver%酒精性脂肪肝中库普弗细胞表型变化的探讨

    Institute of Scientific and Technical Information of China (English)

    程希; 胡超杰; 李晚霞; 黄成; 李俊

    2015-01-01

    detecting the level of serum alanine aminotransferase/glutamic oxalacetic transaminase( ALT/AST) and total cholesterol/triglycerides( TG/TC) , the level of TG/TC of liver tissue homoge-nate and liver pathological section HE and oil red staining. KCs were isolated by in situ perfusion, and the cell yield and cell changes were detected by flow cytometry. Cytokine levels of organization and the primary cell were detected by qRT-PCR. Results The model response to liver injury index of ALT/AST was higher than that of con-trol group,meanwhile HE and oil red staining results were consistent with that. So the alcoholic fatty liver model was successfully established in mice. Cell yield of each mouse was about 1. 5 × 106 ~2. 0 × 106 , KCs were double-labeled by murine macrophage cell surface marker F4/80 molecule and white blood cells surface antigen molecules CD45, F4/80 and CD45 double positive cells were selected to flow analysis. Data showed that natural CD68 + was significantly lower in the model, a large number of the infiltration of mononuclear cells were elevated. Florescent real-time quantitative RT-PCR(qRT-PCR) results showed that cytokine,tumor necrosis factor (TNF-α),interleu-kin-6 ( IL-6 ) , monocyte chemoattractant protein ( MCP-1 ) level increased significantly in liver tissue and primary cell. Conclusion The model of alcoholic fatty liver is successfully established and there is a high yield of cells in situ perfusion. The incidence of alcoholic fatty liver may be relative to hepatic macrophages constitute and pheno-typic changes, associated with elevated cytokine mediated infiltration of peripheral mononuclear cells.

  9. Role of choline deficiency in the Fatty liver phenotype of mice fed a low protein, very low carbohydrate ketogenic diet.

    Directory of Open Access Journals (Sweden)

    Rebecca C Schugar

    Full Text Available Though widely employed for clinical intervention in obesity, metabolic syndrome, seizure disorders and other neurodegenerative diseases, the mechanisms through which low carbohydrate ketogenic diets exert their ameliorative effects still remain to be elucidated. Rodent models have been used to identify the metabolic and physiologic alterations provoked by ketogenic diets. A commonly used rodent ketogenic diet (Bio-Serv F3666 that is very high in fat (~94% kcal, very low in carbohydrate (~1% kcal, low in protein (~5% kcal, and choline restricted (~300 mg/kg provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury. To understand the independent and synergistic roles of protein restriction and choline deficiency on the pleiotropic effects of rodent ketogenic diets, we studied four custom diets that differ only in protein (5% kcal vs. 10% kcal and choline contents (300 mg/kg vs. 5 g/kg. C57BL/6J mice maintained on the two 5% kcal protein diets induced the most significant ketoses, which was only partially diminished by choline replacement. Choline restriction in the setting of 10% kcal protein also caused moderate ketosis and hepatic fat accumulation, which were again attenuated when choline was replete. Key effects of the 5% kcal protein diet - weight loss, hepatic fat accumulation, and mitochondrial ultrastructural disarray and bioenergetic dysfunction - were mitigated by choline repletion. These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation.

  10. Sex hormone binding globulin phenotypes

    DEFF Research Database (Denmark)

    Cornelisse, M M; Bennett, Patrick; Christiansen, M

    1994-01-01

    Human sex hormone binding globulin (SHBG) is encoded by a normal and a variant allele. The resulting SHBG phenotypes (the homozygous normal SHBG, the heterozygous SHBG and the homozygous variant SHBG phenotype) can be distinguished by their electrophoretic patterns. We developed a novel detection....... This method of detection was used to determine the distribution of SHBG phenotypes in healthy controls of both sexes and in five different pathological conditions characterized by changes in the SHBG level or endocrine disturbances (malignant and benign ovarian neoplasms, hirsutism, liver cirrhosis...... on the experimental values. Differences in SHBG phenotypes do not appear to have any clinical significance and no sex difference was found in the SHBG phenotype distribution....

  11. Liver macrophages in healthy and diseased liver.

    Science.gov (United States)

    Abdullah, Zeinab; Knolle, Percy A

    2017-04-01

    Kupffer cells, the largest tissue resident macrophage population, are key for the maintenance of liver integrity and its restoration after injury and infections, as well as the local initiation and resolution of innate and adaptive immunity. These important roles of Kupffer cells were recently identified in healthy and diseased liver revealing diverse functions and phenotypes of hepatic macrophages. High-level phenotypic and genomic analysis revealed that Kupffer cells are not a homogenous population and that the hepatic microenvironment actively shapes both phenotype and function of liver macrophages. Compared to macrophages from other organs, hepatic macrophages bear unique properties that are instrumental for their diverse roles in local immunity as well as liver regeneration. The diverse and, in part, contradictory roles of hepatic macrophages in anti-tumor and inflammatory immune responses as well as regulatory and regenerative processes have been obscured by the lack of appropriate technologies to specifically target or ablate Kupffer cells or monocyte-derived hepatic macrophages. Future studies will need to dissect the exact role of the hepatic macrophages with distinct functional properties linked to their differentiation status and thereby provide insight into the functional plasticity of hepatic macrophages.

  12. Liver Facts

    Science.gov (United States)

    ... Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Liver Facts How the Liver Works The liver is one ... Camps for kids Contacting my donor family Data Facts about living donation Financing a transplant Matching organs ...

  13. DNMT1 is a Required Genomic Regulator for Murine Liver Histogenesis and Regeneration

    DEFF Research Database (Denmark)

    Kaji, Kosuke; Factor, Valentina M; Andersen, Jesper B

    2016-01-01

    conditional knockout mice (Dnmt1(Δalb) ) by crossing Dnmt1(fl/fl) with Albumin-Cre (Alb-Cre) transgenic mice. Serum, liver tissues and primary hepatocytes were collected from 1-20 week old mice. The Dnmt1(Δalb) phenotype was assessed by histology, confocal and electron microscopy, biochemistry as well...... hepatocytes caused global hypomethylation, enhanced DNA damage response and initiated a senescence state causing a progressive inability to maintain tissue homeostasis and proliferate in response to injury. The liver regenerated via activation and repopulation from progenitors due to lineage...... hepatocytes did not affect liver homeostasis. CONCLUSION: These results establish the indispensable role of DNMT1-mediated epigenetic regulation in postnatal liver growth and regeneration. The Dnmt1(Δalb) mice provide a unique experimental model to study the role of senescence and contribution of progenitor...

  14. Glutamatergic signaling maintains the epithelial phenotype of proximal tubular cells

    NARCIS (Netherlands)

    Bozic, M.; de Rooij, J.; Parisi, E.; Ortega, M.R.; Fernandez, E.; Valdivielso, J.M.

    2011-01-01

    Epithelial-mesenchymal transition (EMT) contributes to the progression of renal tubulointerstitial fibrosis. The N-methyl-d-aspartate receptor (NMDAR), which is present in proximal tubular epithelium, is a glutamate receptor that acts as a calcium channel. Activation of NMDAR induces actin rearrange

  15. How Does Nuclear Organization Maintain Normal Mammary Phenotype?

    Science.gov (United States)

    2005-03-01

    with ogy; SAM, Sequence Alignment and Modeling. Article and publication are at http://www.proteinscience.org/cgi/doi/ functions other than mitosis . A...topics: Embryology and Histology 1995: Postdoctoral Fellow Gustave Roussy Cancer Institute (Villejuif, France), and a 3- month training in Dr. Kohwi...protein NuMA, NuMA-CT, has a well-known function in mitosis via its proximal segment, but it seems also involved in the control of differentiation. To

  16. Ergonomics Contribution in Maintainability

    Science.gov (United States)

    Teymourian, Kiumars; Seneviratne, Dammika; Galar, Diego

    2017-09-01

    The objective of this paper is to describe an ergonomics contribution in maintainability. The economical designs, inputs and training helps to increase the maintainability indicators for industrial devices. This analysis can be helpful, among other cases, to compare systems, to achieve a better design regarding maintainability requirements, to improve this maintainability under specific industrial environment and to foresee maintainability problems due to eventual changes in a device operation conditions. With this purpose, this work first introduces the notion of ergonomics and human factors, maintainability and the implementation of assessment of human postures, including some important postures to perform maintenance activities. A simulation approach is used to identify the critical posture of the maintenance personnel and implements the defined postures with minimal loads on the personnel who use the equipment in a practical scenario. The simulation inputs are given to the designers to improve the workplace/equipment in order to high level of maintainability. Finally, the work concludes summarizing the more significant aspects and suggesting future research.

  17. The long-term outcome of patients with polycystic liver disease treated with lanreotide.

    NARCIS (Netherlands)

    Chrispijn, M.; Nevens, F.; Gevers, T.J.G.; Vanslembrouck, R.; Oijen, M.G.H. van; Coudyzer, W.; Hoffmann, A.L.; Dekker, H.M.; Man, R.A. de; Keimpema, L. van; Drenth, J.P.H.

    2012-01-01

    BACKGROUND: Polycystic liver disease (PLD) is a phenotypical expression of autosomal dominant polycystic kidney disease and isolated polycystic liver disease. Somatostatin analogues, such as lanreotide, reduce polycystic liver volume. AIM: To establish long-term outcome and safety of lanreotide.

  18. Mouse phenotyping.

    Science.gov (United States)

    Fuchs, Helmut; Gailus-Durner, Valérie; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Calzada-Wack, Julia; Da Silva-Buttkus, Patricia; Neff, Frauke; Götz, Alexander; Hans, Wolfgang; Hölter, Sabine M; Horsch, Marion; Kastenmüller, Gabi; Kemter, Elisabeth; Lengger, Christoph; Maier, Holger; Matloka, Mikolaj; Möller, Gabriele; Naton, Beatrix; Prehn, Cornelia; Puk, Oliver; Rácz, Ildikó; Rathkolb, Birgit; Römisch-Margl, Werner; Rozman, Jan; Wang-Sattler, Rui; Schrewe, Anja; Stöger, Claudia; Tost, Monica; Adamski, Jerzy; Aigner, Bernhard; Beckers, Johannes; Behrendt, Heidrun; Busch, Dirk H; Esposito, Irene; Graw, Jochen; Illig, Thomas; Ivandic, Boris; Klingenspor, Martin; Klopstock, Thomas; Kremmer, Elisabeth; Mempel, Martin; Neschen, Susanne; Ollert, Markus; Schulz, Holger; Suhre, Karsten; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Hrabě de Angelis, Martin

    2011-02-01

    Model organisms like the mouse are important tools to learn more about gene function in man. Within the last 20 years many mutant mouse lines have been generated by different methods such as ENU mutagenesis, constitutive and conditional knock-out approaches, knock-down, introduction of human genes, and knock-in techniques, thus creating models which mimic human conditions. Due to pleiotropic effects, one gene may have different functions in different organ systems or time points during development. Therefore mutant mouse lines have to be phenotyped comprehensively in a highly standardized manner to enable the detection of phenotypes which might otherwise remain hidden. The German Mouse Clinic (GMC) has been established at the Helmholtz Zentrum München as a phenotyping platform with open access to the scientific community (www.mousclinic.de; [1]). The GMC is a member of the EUMODIC consortium which created the European standard workflow EMPReSSslim for the systemic phenotyping of mouse models (http://www.eumodic.org/[2]). Copyright © 2010 Elsevier Inc. All rights reserved.

  19. Maintaining Learners’Motivation

    Institute of Scientific and Technical Information of China (English)

    SI Zi-han

    2015-01-01

    Foreign language learning is a complex process and its success is determined by a variety of factors. The prime one of them is motivation ,which, as everyone knows, could be controlled by external forces so as to be taken advantage of. Motivation could prompt the learner to have his own learning goals and let him finish his learning task autonomously. All of that shows the im⁃portance of maintaining learners’motivation. This paper will demonstrate not only the definition and the types of motivation, but al⁃so the methods that could be used to stimulate and maintain the motivation.

  20. Liver biopsy

    Science.gov (United States)

    Biopsy - liver; Percutaneous biopsy ... the biopsy needle to be inserted into the liver. This is often done by using ultrasound. The ... the chance of damage to the lung or liver. The needle is removed quickly. Pressure will be ...

  1. Liver Hemangioma

    Science.gov (United States)

    ... in your liver, even if it's a benign mass. There's no evidence that an untreated liver hemangioma can lead to liver ... of Nondiscrimination Advertising Mayo Clinic is a not-for-profit organization ...

  2. Possible role of macrophage phenotype transition in pathogenesis of non-alcoholic fatty liver disease%巨噬细胞表型转换在NAFLD发生过程中的可能作用

    Institute of Scientific and Technical Information of China (English)

    邵小娟; 王晓敏; 王斌; 熊吉; 李青; 陈东风

    2013-01-01

    目的 探讨非酒精性脂肪性肝病(NAFLD)患者网膜脂肪、皮下脂肪中巨噬细胞数量及不同表型,以及其与NAFLD严重程度的关系及意义.方法 选择2012年4~12月于第三军医大学大坪医院野战外科研究所住院的NAFLD伴单纯性胆囊结石患者27例(NAFLD组),以及同期单纯性胆囊结石但排除NAFLD及其他一切肝病的肝功能正常的单纯性胆囊结石患者28例(非NAFLD组).对两组患者的年龄、性别、体质量指数(BMI)、腹围、血糖、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、三酰甘油(TG)、胰岛素抵抗指数(HOMA-IR)、胰岛素、游离脂肪酸(FFA)进行比较.使用CD68标记巨噬细胞、CD11C标记M1亚群巨噬细胞,CD206标记M2亚群巨噬细胞,免疫组织化学染色检测其网膜脂肪组织、皮下脂肪组织的巨噬细胞及M1亚群,M2亚群数量.结果 NAFLD组和非NAFLD组的年龄、性别、腹围、血糖、ALT、AST、总胆红素(TB)、FFA比较,差异无统计学意义(P>0.05).而BMI、胰岛素、HOMA指数、TG在NAFLD组明显高于非NAFLD组,差异有统计学意义(P0.05).结论 NAFLD患者存在胰岛素抵抗及血脂代谢紊乱,网膜脂肪及皮下脂肪中的巨噬细胞数量及其表型转换可能参与了NAFLD的疾病进展.%Objective To research the number of macrophage and macrophage phenotype transition in epiploic adipose tissue and subcutaneous adipose tissue in non-alcoholic fatty liver disease (NAFLD ) and their relation with the severity of NAFLD and signifi -cance .Methods 27 cases of NAFLD complicated with simple cholelithiasis admitted to the Daping Hospital affiliated to Third Mill -tary Medical University from April to December 2012 were selected as the NAFLD group .Contemporaneous 28 cases of simple cholelithiasis excluding NAFLD and other liver disease with normal liver function were used as the non-NAFLD group .Age ,sex ,BMI, abdominal circumference ,glucose ,ALT ,AST ,TG ,H0M A -IR ,and

  3. Economy Maintains Good Health

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    China’s national economy has maintained rapid even growth in the first half of 2007, according to Xie Fuzhan, Commissioner of the National Bureau of Statistics. He was referring to major economic indicators of the January-June period that reveal that Chi

  4. Maintaining cell identity

    DEFF Research Database (Denmark)

    Comet, Itys; Riising, Eva M; Leblanc, Benjamin

    2016-01-01

    trials. Several observations show that PRC2 can have both oncogenic and tumour-suppressive functions. We propose that these apparently opposing roles of PRC2 in cancer are a consequence of the molecular function of the complex in maintaining, rather than specifying, the transcriptional repression state...

  5. 综合保温措施在晚期肝泡状棘球蚴病自体肝移植围术期的应用%Application of comprehensive thermal insulation measures for maintaining body temperature during period of liver transplantation

    Institute of Scientific and Technical Information of China (English)

    李丽; 罗新玲; 陈晓晴; 王梅新

    2015-01-01

    目的:探讨综合保温措施在晚期肝泡状棘球蚴病自体肝移植围术期的应用效果,为提高手术成功率提供理论依据。方法选取18例晚期肝泡状棘球蚴病行自体肝移植术的患者,采用适度提高室温、身体包裹、输液加温、湿敷料加温、冲洗液加温与铺置保温毯的综合保温措施,通过监测肛温、鼻咽温、心率、血压、pH值,验证此法是否有效。结果在新肝再灌注5 min时,患者鼻咽温、肛温分别为:(35.78±0.69),(35.97±0.65)℃,pH值为(7.29±0.08),均显著下降;心率加快为(100.58±5.47)次/min,差异有统计学意义(P<0.01)。在无肝期后30 min和新肝再灌注5 min时,收缩压分别为(82.21±10.45),(83.59±12.71)mmHg,均显著下降,差异有统计学意义(P<0.01);以上指标均在新肝再灌注30 min后恢复正常。结论在晚期肝泡状棘球蚴病自体肝移植围术期,综合保温措施的应用能有效地预防术中低体温的发生。%Objective To evaluate the effects of comprehensive thermal insulation measure for maintaining body temperature during perioperative period of liver transplantation for the late hepatic alveolar echinococcosis, and provide theoretical basis for improving the success rate of the operation. Methods A total of 18 patients undergoing liver transplantation for the late hepatic alveolar echinococcosis received comprehensive thermal insulation measure. The changes of nasopharyngeal and rectal temperature, pH, heart rate and blood pressure were monitored in the whole process of operation to justify the effective. Results After 5 min the new liver reperfusion, the nasopharyngeal and rectal temperature were (35. 78 ± 0. 69) and (35. 97 ± 0. 65)℃, and the value of pH decreased dramatically to (7. 29 ± 0. 08), but the heart rate increased to (100. 58 ± 5. 47) times/min (P<0. 01). The systolic blood pressure were (82. 21 ± 10. 45) and (83. 59 ± 12. 71) mmHg during no liver period and 5 min new liver

  6. Investigation on“Liver Maintaining the Free Flow of Qi”in the Healthy U-niversity Female Students in Four Seasons%健康女大学生四时节令“肝主疏泄”功能状况调查研究

    Institute of Scientific and Technical Information of China (English)

    赵勇; 杜彩凤; 梁文静; 谷加族; 赵燕

    2015-01-01

    Objective To explore the difference in the physiological manifestations in four seasons in terms of“liver maintaining the free flow of qi”. Methods The approach and method of clinical epidemiol-ogy were adopted. The vernal equinox,summer solstice,autumn equinox and winter solstice were taken as four observation time points. In the physical and psychological aspects,the follow - up observation was done in the sophomore healthy female students. Results In the sophomore healthy female students,in the physical and psychological dimensions,the score of manifestations in winter solstice was the highest and that was of the second top in summer solstice. The score was relatively low in vernal equinox and autumn equinox. Conclu-sion “Liver maintaining the free flow of qi”is theoretic collaborated with“the correspondence of five zang organs with four seasons”. By the longitudinal follow - up investigation in the healthy female students,it is found that“liver maintaining the free flow of qi”is constantly changeable with the growth and storage of yang qi in four seasons,which provides the evidence to investigate the law of“liver maintaining the free flow of qi”with the seasonal changes.%目的:探讨“肝主疏泄”功能随四时节令变化在生理表现上的差异性。方法运用临床流行病学调查的手段和方法,选择春分、夏至、秋分、冬至四个节令作为四季的观察时点,从躯体、心理两个层面,对大学二年级健康女学生进行追踪观察。结果处于健康状态的大二女学生,在躯体和心理两个维度,表现出冬至得分最高,夏至得分次之,春分、秋分得分相对较低的状况。结论将“肝主疏泄”与“五脏应四时”的理论相结合,通过对健康女大学生的纵向追踪调查,发现“肝主疏泄”的功能随四时节令阳气生长收藏而不断变化,为进一步探讨“肝主疏泄”的功能随四时节令变化的规律提供了一定的依据。

  7. Mouse embryonic fibroblasts derived from Odin deficient mice display a hyperproliiferative phenotype

    DEFF Research Database (Denmark)

    Kristiansen, Troels Zaccharias Glahn; Nielsen, Mogens Møller; Blagoev, Blagoy

    2004-01-01

    as a KIAA clone (KIAA 0229) from the Kazusa DNA Research Institute which maintains the HUGE protein database--a database devoted to the analysis of long cDNA clones encoding large proteins (>50 kDa). Odin has been demonstrated to cause downregulation of c-Fos promoter activity and to inhibit PDGF...... of the kidney, lung and liver does not show any major abnormalities as compared to wild-type controls. However, mouse embryonic fibroblasts (MEFs) generated from Odin-deficient mice exhibit a hyperproliferative phenotype compared to wild-type-derived MEFs, consistent with its role as a negative regulator...

  8. Hypoxia and fatty liver.

    Science.gov (United States)

    Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito

    2014-11-07

    The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty liver disease, a major cause of chronic liver diseases worldwide, ranging from simple steatosis, through steatohepatitis and hepatic fibrosis, to liver cirrhosis. Altered hepatic metabolism and tissue remodeling in fatty liver disease further disrupt hepatic oxygen homeostasis, resulting in severe liver hypoxia. As master regulators of adaptive responses to hypoxic stress, hypoxia-inducible factors (HIFs) modulate various cellular and organ functions, including erythropoiesis, angiogenesis, metabolic demand, and cell survival, by activating their target genes during fetal development and also in many disease conditions such as cancer, heart failure, and diabetes. In the past decade, it has become clear that HIFs serve as key factors in the regulation of lipid metabolism and fatty liver formation. This review discusses the molecular mechanisms by which hypoxia and HIFs regulate lipid metabolism in the development and progression of fatty liver disease.

  9. Nuclear power plant maintainability.

    Science.gov (United States)

    Seminara, J L; Parsons, S O

    1982-09-01

    In the mid-1970s a general awareness of human factors engineering deficiencies associated with power plant control rooms took shape and the Electric Power Research Institute (EPRI) awarded the Lockheed Corporation a contract to review the human factors aspects of five representative operational control rooms and their associated simulators. This investigation revealed a host of major and minor deficiencies that assumed unforeseen dimensions in the post- Three Mile Island accident period. In the course of examining operational problems (Seminara et al, 1976) and subsequently the methods for overcoming such problems (Seminara et al, 1979, 1980) indications surfaced that power plants were far from ideal in meeting the needs of maintenance personnel. Accordingly, EPRI sponsored an investigation of the human factors aspects of power plant maintainability (Seminara, 1981). This paper provides an overview of the maintainability problems and issues encountered in the course of reviewing five nuclear power plants.

  10. Direct bonded space maintainers.

    Science.gov (United States)

    Santos, V L; Almeida, M A; Mello, H S; Keith, O

    1993-01-01

    The aim of this study was to evaluate clinically a bonded space maintainer, which would reduce chair-side time and cost. Sixty appliances were fabricated from 0.7 mm stainless steel round wire and bonded using light-cured composite to the two teeth adjacent to the site of extraction of a posterior primary tooth. Twenty males and sixteen females (age range 5-9-years-old) were selected from the Pedodontic clinic of the State University of Rio de Janeiro. The sixty space maintainers were divided into two groups according to the site in which they were placed: a) absent first primary molar and b) absent second primary molar. Impressions and study models were obtained prior to and 6 months after bonding the appliances. During this period only 8.3% of failures were observed, most of them from occlusal or facial trauma. Student t-test did not show statistically significant alterations in the sizes of the maintained spaces during the trial period.

  11. Successful transplantation of human hepatic stem cells with restricted localization to liver using hyaluronan grafts.

    Science.gov (United States)

    Turner, Rachael A; Wauthier, Eliane; Lozoya, Oswaldo; McClelland, Randall; Bowsher, James E; Barbier, Claire; Prestwich, Glenn; Hsu, Edward; Gerber, David A; Reid, Lola M

    2013-02-01

    Cell therapies are potential alternatives to organ transplantation for liver failure or dysfunction but are compromised by inefficient engraftment, cell dispersal to ectopic sites, and emboli formation. Grafting strategies have been devised for transplantation of human hepatic stem cells (hHpSCs) embedded into a mix of soluble signals and extracellular matrix biomaterials (hyaluronans, type III collagen, laminin) found in stem cell niches. The hHpSCs maintain a stable stem cell phenotype under the graft conditions. The grafts were transplanted into the livers of immunocompromised murine hosts with and without carbon tetrachloride treatment to assess the effects of quiescent versus injured liver conditions. Grafted cells remained localized to the livers, resulting in a larger bolus of engrafted cells in the host livers under quiescent conditions and with potential for more rapid expansion under injured liver conditions. By contrast, transplantation by direct injection or via a vascular route resulted in inefficient engraftment and cell dispersal to ectopic sites. Transplantation by grafting is proposed as a preferred strategy for cell therapies for solid organs such as the liver.

  12. Designing a multicellular organotypic 3D liver model with a detachable, nanoscale polymeric Space of Disse.

    Science.gov (United States)

    Larkin, Adam L; Rodrigues, Richard R; Murali, T M; Rajagopalan, Padmavathy

    2013-11-01

    The design of in vitro models that mimic the stratified multicellular hepatic microenvironment continues to be challenging. Although several in vitro hepatic cultures have been shown to exhibit liver functions, their physiological relevance is limited due to significant deviation from in vivo cellular composition. We report the assembly of a novel three-dimensional (3D) organotypic liver model incorporating three different cell types (hepatocytes, liver sinusoidal endothelial cells, and Kupffer cells) and a polymeric interface that mimics the Space of Disse. The nanoscale interface is detachable, optically transparent, derived from self-assembled polyelectrolyte multilayers, and exhibits a Young's modulus similar to in vivo values for liver tissue. Only the 3D liver models simultaneously maintain hepatic phenotype and elicit proliferation, while achieving cellular ratios found in vivo. The nanoscale detachable polymeric interfaces can be modulated to mimic basement membranes that exhibit a wide range of physical properties. This facile approach offers a versatile new avenue in the assembly of engineered tissues. These results demonstrate the ability of the tri-cellular 3D cultures to serve as an organotypic hepatic model that elicits proliferation and maintenance of phenotype and in vivo-like cellular ratios.

  13. Liver regeneration.

    Science.gov (United States)

    Mao, Shennen A; Glorioso, Jaime M; Nyberg, Scott L

    2014-04-01

    The liver is unique in its ability to regenerate in response to injury. A number of evolutionary safeguards have allowed the liver to continue to perform its complex functions despite significant injury. Increased understanding of the regenerative process has significant benefit in the treatment of liver failure. Furthermore, understanding of liver regeneration may shed light on the development of cancer within the cirrhotic liver. This review provides an overview of the models of study currently used in liver regeneration, the molecular basis of liver regeneration, and the role of liver progenitor cells in regeneration of the liver. Specific focus is placed on clinical applications of current knowledge in liver regeneration, including small-for-size liver transplant. Furthermore, cutting-edge topics in liver regeneration, including in vivo animal models for xenogeneic human hepatocyte expansion and the use of decellularized liver matrices as a 3-dimensional scaffold for liver repopulation, are proposed. Unfortunately, despite 50 years of intense study, many gaps remain in the scientific understanding of liver regeneration.

  14. Natural killer cells in liver disease

    National Research Council Canada - National Science Library

    Tian, Zhigang; Chen, Yongyan; Gao, Bin

    2013-01-01

    Natural killer (NK) cells are enriched in lymphocytes within the liver and have unique phenotypic features and functional properties, including tumor necrosis factor–related apoptosis‐inducing ligand...

  15. Liver replacement for alpha1-antitrypsin deficiency

    Science.gov (United States)

    Putnam, Charles W.; Porter, Kendrick A.; Peters, Robert L.; Ashcavai, Mary; Redeker, Allan G.; Starzl, Thomas E.

    2010-01-01

    A 16-year-old girl with advanced cirrhosis and severe alpha1-antitrypsin deficiency of the homozygous PiZZ phenotype was treated by orthotopic liver transplantation. After replacement of the liver with a homograft from a donor with the normal PiMM phenotype, the alpha1-antitrypsin concentration in the recipient’s serum rose to normal; it had the PiMM phenotype. Two and a third years later, chronic rejection necessitated retransplantation. Insertion of a homograft from a heterozygous PiMZ donar was followed by the identification of that phenotype in the recipient’s serum. Neither liver graft developed the alpha1-antitrypsin glycoprotein deposits seen with the deficiency state. These observations confirm that this hepatic- based inborn error metabolism is metabolically cured by liver replacement. PMID:320694

  16. Human Ex-Vivo Liver Model for Acetaminophen-induced Liver Damage

    Science.gov (United States)

    Schreiter, Thomas; Sowa, Jan-Peter; Schlattjan, Martin; Treckmann, Jürgen; Paul, Andreas; Strucksberg, Karl-Heinz; Baba, Hideo A.; Odenthal, Margarete; Gieseler, Robert K.; Gerken, Guido; Arteel, Gavin E.; Canbay, Ali

    2016-01-01

    Reliable test systems to identify hepatotoxicity are essential to predict unexpected drug-related liver injury. Here we present a human ex-vivo liver model to investigate acetaminophen-induced liver injury. Human liver tissue was perfused over a 30 hour period with hourly sampling from the perfusate for measurement of general metabolism and clinical parameters. Liver function was assessed by clearance of indocyanine green (ICG) at 4, 20 and 28 hours. Six pieces of untreated human liver specimen maintained stable liver function over the entire perfusion period. Three liver sections incubated with low-dose acetaminophen revealed strong damage, with ICG half-lives significantly higher than in non-treated livers. In addition, the release of microRNA-122 was significantly higher in acetaminophen-treated than in non-treated livers. Thus, this model allows for investigation of hepatotoxicity in human liver tissue upon applying drug concentrations relevant in patients. PMID:27550092

  17. Liver Immunology

    Science.gov (United States)

    Bogdanos, Dimitrios P.; Gao, Bin; Gershwin, M. Eric

    2014-01-01

    The liver is the largest organ in the body and is generally regarded by non-immunologists as not having lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates a tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and is also instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena which if are not controlled by regulatory lymphoid populations may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events which lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discus select, but not all, immune mediated liver disease and attempt to place these data in the context of human autoimmunity. PMID:23720323

  18. Liver Diseases

    Science.gov (United States)

    Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases: Diseases caused by viruses, such as hepatitis ...

  19. Fatty Liver

    Science.gov (United States)

    ... Abbreviations Weights & Measures ENGLISH View Professional English Deutsch Japanese Espaniol Find information on medical topics, symptoms, drugs, ... inside liver cells. Just consuming a high-fat diet does not result in fatty liver. Rarely, fat ...

  20. Liver disease

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000205.htm Liver disease To use the sharing features on this page, please enable JavaScript. The term "liver disease" applies to many conditions that stop the ...

  1. Liver Disease

    Science.gov (United States)

    ... stay still. Liver disease has many causes. Infection Parasites and viruses can infect the liver, causing inflammation ... beyond. National Institute of Diabetes and Digestive and Kidney Diseases. http://digestive.niddk.nih.gov/ddiseases/pubs/ ...

  2. Maintaining Web Cache Coherency

    Directory of Open Access Journals (Sweden)

    2000-01-01

    Full Text Available Document coherency is a challenging problem for Web caching. Once the documents are cached throughout the Internet, it is often difficult to keep them coherent with the origin document without generating a new traffic that could increase the traffic on the international backbone and overload the popular servers. Several solutions have been proposed to solve this problem, among them two categories have been widely discussed: the strong document coherency and the weak document coherency. The cost and the efficiency of the two categories are still a controversial issue, while in some studies the strong coherency is far too expensive to be used in the Web context, in other studies it could be maintained at a low cost. The accuracy of these analysis is depending very much on how the document updating process is approximated. In this study, we compare some of the coherence methods proposed for Web caching. Among other points, we study the side effects of these methods on the Internet traffic. The ultimate goal is to study the cache behavior under several conditions, which will cover some of the factors that play an important role in the Web cache performance evaluation and quantify their impact on the simulation accuracy. The results presented in this study show indeed some differences in the outcome of the simulation of a Web cache depending on the workload being used, and the probability distribution used to approximate updates on the cached documents. Each experiment shows two case studies that outline the impact of the considered parameter on the performance of the cache.

  3. Modified bonded bridge space maintainer.

    Science.gov (United States)

    Liegeois, F; Limme, M

    1999-01-01

    The premature loss of primary teeth can create the need for space maintenance and restoration of function. This article presents a fixed bonded space maintainer, which allows space to be maintained with economy of dental tissues.

  4. Assessing optimal software architecture maintainability

    NARCIS (Netherlands)

    Bosch, Jan; Bengtsson, P.O.; Smedinga, Rein; Sousa, P; Ebert, J

    2000-01-01

    Over the last decade, several authors have studied the maintainability of software architectures. In particular, the assessment of maintainability has received attention. However, even when one has a quantitative assessment of the maintainability of a software architecture, one still does not have

  5. Assessing optimal software architecture maintainability

    NARCIS (Netherlands)

    Bosch, Jan; Bengtsson, P.O.; Smedinga, Rein; Sousa, P; Ebert, J

    2000-01-01

    Over the last decade, several authors have studied the maintainability of software architectures. In particular, the assessment of maintainability has received attention. However, even when one has a quantitative assessment of the maintainability of a software architecture, one still does not have a

  6. Benign Liver Tumors

    Science.gov (United States)

    ... A Life After Diagnosis Support for Chronic Illness Corporate Partnerships Interview with Kristen Hanks Liver Lowdown July ... Disease , Liver Transplant , Liver Cancer , Liver Tumor , Liver Failure Help Fight Liver Disease We rely upon donations ...

  7. What Is Liver Cancer?

    Science.gov (United States)

    ... Research? Liver Cancer About Liver Cancer What Is Liver Cancer? Cancer starts when cells in the body ... structure and function of the liver. About the liver The liver is the largest internal organ. It ...

  8. Genetic and somatic effects in animals maintained on tritiated water

    Energy Technology Data Exchange (ETDEWEB)

    Carsten, A.L.; Brooks, A.; Commerford, S.L.; Cronkite, E.P.

    1981-01-01

    The possible genetic (dominant lethal mutations (DLM) and cytogenetic changes in the regenerating liver) and somatic (hematopoietic stem cell changes, growth and nonspecific life time shortening) effects in mice maintained on tritiated water (HTO) over two generations was investigated. Results to date are summarized. (ACR)

  9. Ventilatory strategy during liver transplantation

    DEFF Research Database (Denmark)

    Sørensen, Henrik; Grocott, Hilary P; Niemann, Mads

    2014-01-01

    BACKGROUND: As measured by near infrared spectroscopy (NIRS), cerebral oxygenation (ScO2) may be reduced by hyperventilation in the anhepatic phase of liver transplantation surgery (LTx). Conversely, the brain may be subjected to hyperperfusion during reperfusion of the grafted liver. We investig......, this retrospective analysis suggests that attention to maintain a targeted EtCO2 would result in a more stable ScO2 during the operation....

  10. Isolation of epithelial cells with hepatobiliary phenotype.

    Science.gov (United States)

    Castorina, Sergio; Luca, Tonia; Torrisi, Antonella; Privitera, Giovanna; Panebianco, Mariangela

    2008-01-01

    The regenerative capacity of the liver after partial hepatectomy or chemical injury is well known. In human liver, the resident progenitor cells are called "hepatic progenitor cells" (HPCs) while the term "oval cells" should be discouraged in order to indicate the stem cell compartment. The aim of our study was first to analyse the cellular aspects of liver regeneration through differentiation in cholangiocytes and hepatocytes, and then to characterise resident progenitor cells, using "primary cultured hepatocytes" derived from healthy adult human livers. Human hepatocytes were isolated from fresh surgical specimens of patients who underwent hepatic resections in our Clinical Centre surgery operating room. Hepatic differentiation and function were analysed by immunocytochemistry techniques and the presence of liver epithelial cell populations within normal adult human liver, was demonstrated by immunohistochemistry analysis. These cells expanded in vitro and showed the capacity for self-renewal and multipotent differentiation. Human liver stem cells expressed several mesenchymal markers, such as CD44, but not haematopoietic stem cell markers. In addition, these cells expressed alpha-fetoprotein, albumin, CK7 and CK19, indicating a partial commitment to hepatic and biliary cells. Interestingly the expression of both hepatocytes and biliary markers in HPCs reflects the bipotential nature of the hepatic stem cells toward both the hepatic and biliary lineage. According to their immature and bipotential phenotype, hepatic epithelial cells might represent a pool of precursors in the healthy human adult liver.

  11. Liver Transplant

    Science.gov (United States)

    ... Liver Disease & NASH Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Biliary Atresia Cirrhosis Hemochromatosis Hepatitis A through E (Viral Hepatitis) Hepatitis ...

  12. Liver anatomy.

    Science.gov (United States)

    Abdel-Misih, Sherif R Z; Bloomston, Mark

    2010-08-01

    Understanding the complexities of the liver has been a long-standing challenge to physicians and anatomists. Significant strides in the understanding of hepatic anatomy have facilitated major progress in liver-directed therapies--surgical interventions, such as transplantation, hepatic resection, hepatic artery infusion pumps, and hepatic ablation, and interventional radiologic procedures, such as transarterial chemoembolization, selective internal radiation therapy, and portal vein embolization. Without understanding hepatic anatomy, such progressive interventions would not be feasible. This article reviews the history, general anatomy, and the classification schemes of liver anatomy and their relevance to liver-directed therapies. Copyright 2010 Elsevier Inc. All rights reserved.

  13. Effect of Autophagy Over Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    Dong-qian Yi; Xue-feng Yang; Duan-fang Liao; Qing Wu; Nian Fu; Yang Hu; Ting Cao

    2016-01-01

    Abstract In recent years, increasingly evidences show that autophagy plays an important role in the pathogenesis and development of liver diseases, and the relationship between them has increasingly become a focus of concern. Autophagy refers to the process through which the impaired organelles, misfolded protein, and intruding microorganisms is degraded by lysosomes to maintain stability inside cells. This article states the effect of autophagy on liver diseases (hepatic fibrosis, fatty liver, viral hepatitis, and liver cancer), which aims to provide a new direction for the treatment of liver diseases.

  14. Liver spots

    Science.gov (United States)

    Liver spots are changes in skin color that occur in older skin. The coloring may be due to aging, exposure to the sun or other sources of ultraviolet light, or causes that are not known. Liver spots are very common after age 40. They occur ...

  15. [Anaesthesia in connection with liver transplantation

    DEFF Research Database (Denmark)

    Secher, N.H.; Nissen, P.; Swiatek, F.A.;

    2008-01-01

    The anaesthetic plan for liver transplantation focuses on maintaining central blood volume and thereby cerebral oxygenation. Normovolaemia represents a central blood volume that establishes a maximal venous oxygen saturation, and a value of 85% (78-90%) is maintained during the operation by admin......The anaesthetic plan for liver transplantation focuses on maintaining central blood volume and thereby cerebral oxygenation. Normovolaemia represents a central blood volume that establishes a maximal venous oxygen saturation, and a value of 85% (78-90%) is maintained during the operation...

  16. [Anaesthesia in connection with liver transplantation

    DEFF Research Database (Denmark)

    Secher, N.H.; Nissen, P.; Swiatek, F.A.

    2008-01-01

    The anaesthetic plan for liver transplantation focuses on maintaining central blood volume and thereby cerebral oxygenation. Normovolaemia represents a central blood volume that establishes a maximal venous oxygen saturation, and a value of 85% (78-90%) is maintained during the operation by admin......The anaesthetic plan for liver transplantation focuses on maintaining central blood volume and thereby cerebral oxygenation. Normovolaemia represents a central blood volume that establishes a maximal venous oxygen saturation, and a value of 85% (78-90%) is maintained during the operation...

  17. Stopping Liver Cancer's Rogue COP | Center for Cancer Research

    Science.gov (United States)

    Liver cancer is the fourth most common cancer type and the third leading cause of cancer death worldwide. Many liver tumors are actually metastases, tumors seeded in the liver by cancer cells from another organ, but hepatocellular carcinomas (HCCs), the most common liver tumors, are a heterogeneous family of cancers that arise in hepatocytes, the functional cells of the liver. HCCs are often associated with cirrhosis or liver scarring. Because of the variation in tumor phenotypes, the poor understanding of the molecular origins of these tumors, and the increasing number of diagnoses especially in the US, HCC is a major clinical challenge.

  18. Notochordal cells maintain the proliferation and phenotype of chondrocyte-like cells in the disc nucleus pulposus%脊索细胞维持椎间盘髓核软骨样细胞增殖与表型的研究进展

    Institute of Scientific and Technical Information of China (English)

    杨哲; 李树文

    2016-01-01

    BACKGROUND:The immature disc nucleus pulposus is composed of notochordal cels, but there is no notochordal cel in the mature human intervertebral disc, in which the notochordal cels are replaced by chondrocyte-like cels. It is very important to comprehend the disappearance of the notochordal cels; however, it is stil unknown at present. OBJECTIVE: To elaborate the feasibility of notochordal cels to maintain the proliferation and phenotype of chondrocyte-like cels and to induce the cartilage-like differentiation of bone marrow mesenchymal stem cels. METHODS: The first author used the computer to retrieve PubMed and Wanfang databases using the key words of “notochord cels; nucleus pulposus cels; identify” in English and Chinese, respectively. Totaly 9 896 relevant articles published from January 1999 to August 2015 were retrieved. Repetitive studies were excluded, and finaly 36 articles were in accordance with the inclusion criteria. RESULTS AND CONCLUSION:Now, the main functions of notochordal cels are to promote synthesis of extracelular matrix in the nucleus pulposus, induce directional differentiation of mesenchymal cels into nucleus pulposus cels or act as “seed cels” to form the nucleus pulposus cels. The presence and disappearance of notochordal cels is related to intervertebral disc degeneration. Cel apoptosis is involved in static compressionviadeath receptor signals, and then leads to intervertebral disc degeneration. fas ligand can mediate the reduction of notochordal cels, and hypoxia-inducible factor can induce spinal cord injury thereby triggering cel death and complete disappearance of nucleus pulposus. The measurement and verification of immune makers of notochordal cels, CK-8, CK-18 and galectin-3, can benefit to the identification and isolation of notochordal cels, and thereby help the studies on cel growth and differentiation, function and its mechanism of apoptosis.%背景:未成熟的椎间盘髓核是由脊索细胞所组成,但在

  19. Liver metastases

    Science.gov (United States)

    ... no symptoms. When symptoms occur, they may include: Decreased appetite Confusion Fever , sweating Jaundice (yellowing of the skin ... can include: Blockage of the flow of bile Decreased appetite Fever Liver failure (usually only in the late ...

  20. Liver Panel

    Science.gov (United States)

    ... GGT) – another enzyme found mainly in liver cells Lactate dehydrogenase (LD) – an enzyme released with cell damage; found ... and with conditions, such as congestive heart failure . Lactate dehydrogenase (LD) This is a non-specific marker of ...

  1. Liver function

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008308 Study on transplantation of induced bone marrow mesenchymal stem cells via a series of the treatment of chronic liver injury. SUN Yan(孙艳), et al. Dept Gastroenterol, 1st Hosp, Jilin Univ, Changchun 130021. Chin J Dig 2008;28(3):171-174.Objective To investigate the efficacy of transplantation of induced bone marrow mesenchymal stem cells(MSCs)via a series of treatment of chronic liver injury.Methods MSCs were isolated and expanded by density

  2. A Novel Polarization Maintaining Fiber

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    It introduces a novel elliptical jacket polarization maintaining fiber, whose SAP is like numeral "1". One preform can be drawn over 8km. Fiber's performances show that it is fit for fiber gyroscope and other sensors.

  3. A Novel Polarization Maintaining Fiber

    Institute of Scientific and Technical Information of China (English)

    Benjamin Xue

    2003-01-01

    It introduces a novel elliptical jacket polarization maintaining fiber, whose SAP is like numeral "1" One preform can be drawn over 8km. Fiber's performances show that it is fit for fiber gyroscope and other sensors.

  4. Simple fixed functional space maintainer.

    Science.gov (United States)

    Goenka, Puneet; Sarawgi, Aditi; Marwah, Nikhil; Gumber, Parvind; Dutta, Samir

    2014-01-01

    Premature loss of a primary tooth is one of the most common etiology for malocclusion. Space maintainers are employed to prevent this complication. In anterior region, esthetics is an important concern along with function and space management. Fiber-reinforced composite (FRC) retained space maintainer solves all these purposes ef ficiently and ef fectively. In addition, the technique is simple and the appliance is very comfortable inside the oral cavity. Here is a case of premature loss of anterior primary tooth which was replaced by FRC retained esthetic functional space maintainer. The appliance was found to be functioning satisfactorily inside the oral cavity till the last visit (1 Year). How to cite this article: Goenka P, Sarawgi A, Marwah N, Gumber P, Dutta S. Simple Fixed Functional Space Maintainer. Int J Clin Pediatr Dent 2014;7(3):225-228.

  5. Marshal: Maintaining Evolving Models Project

    Data.gov (United States)

    National Aeronautics and Space Administration — SIFT proposes to design and develop the Marshal system, a mixed-initiative tool for maintaining task models over the course of evolving missions. Marshal-enabled...

  6. How to maintain improved cultivars

    NARCIS (Netherlands)

    Parlevliet, J.E.

    2007-01-01

    Improved cultivars loose their identity and healthiness unless maintained properly. Contaminating and degrading forces, such as outcrossing, volunteer plants, mixing, natural selection, mutation and seed-borne diseases, are at the root of this. Maintenance selection can prevent this deterioration.

  7. Simple Fixed Functional Space Maintainer

    OpenAIRE

    Goenka, Puneet; Sarawgi, Aditi; Marwah, Nikhil; Gumber, Parvind; Dutta, Samir

    2015-01-01

    ABSTRACT% Premature loss of a primary tooth is one of the most common etiology for malocclusion. Space maintainers are employed to prevent this complication. In anterior region, esthetics is an important concern along with function and space management. Fiber-reinforced composite (FRC) retained space maintainer solves all these purposes ef ficiently and ef fectively. In addition, the technique is simple and the appliance is very comfortable inside the oral cavity. Here is a case of premature ...

  8. Liver allograft pathology in healthy pediatric liver transplant recipients.

    Science.gov (United States)

    Briem-Richter, Andrea; Ganschow, Rainer; Sornsakrin, Marijke; Brinkert, Florian; Schirmer, Jan; Schaefer, Hansjörg; Grabhorn, Enke

    2013-09-01

    Liver transplantation offers excellent results for children with end-stage liver disease, and efforts should be directed toward maintaining long-term graft health. We evaluate graft pathology in healthy pediatric transplant recipients with low-maintenance immunosuppressive medications to assess whether protocol biopsies are helpful for adapting immunosuppression and protecting long-term graft function. Liver biopsies were performed on 60 healthy pediatric liver transplant recipients, and histological findings were correlated with laboratory, serological, and radiological results. Fourteen patients (23%) were diagnosed with acute or early chronic rejection, and immunosuppressive medications were increased in these children. Liver function tests did not correlate with histological findings. The incidence of fibrosis was 36% in transplant recipients five or more years after liver transplantation. We observed an unexpectedly high prevalence of rejection and fibrosis in children with no laboratory abnormalities, which led to changes in their immunosuppressive medications. Scheduled biopsies appear to be useful in pediatric transplant recipients with low immunosuppressive medications for early detection of morphological changes in liver transplants. Further studies are needed to evaluate whether adaption of immunosuppression helps to reduce tissue damage and the incidence of allograft dysfunction in the long term.

  9. PAFR in adipose tissue macrophages is associated with anti-inflammatory phenotype and metabolic homoeostasis.

    Science.gov (United States)

    Filgueiras, Luciano Ribeiro; Koga, Marianna Mainardi; Quaresma, Paula G; Ishizuka, Edson Kiyotaka; Montes, Marlise B A; Prada, Patricia O; Saad, Mario J; Jancar, Sonia; Rios, Francisco J

    2016-04-01

    Metabolic dysfunction is associated with adipose tissue inflammation and macrophage infiltration. PAFR (platelet-activating factor receptor) is expressed in several cell types and binds to PAF (platelet-activating factor) and oxidized phospholipids. Engagement of PAFR in macrophages drives them towards the anti-inflammatory phenotype. In the present study, we investigated whether genetic deficiency of PAFR affects the phenotype of ATMs (adipose tissue macrophages) and its effect on glucose and insulin metabolism. PARFKO (PAFR-knockout) and WT (wild-type) mice were fed on an SD (standard diet) or an HFD (high-fat diet). Glucose and insulin tolerance tests were performed by blood monitoring. ATMs were evaluated by FACS for phenotypic markers. Gene and protein expression was investigated by real-time reverse transcription-quantitative PCR and Western blotting respectively. Results showed that the epididymal adipose tissue of PAFRKO mice had increased gene expression of Ccr7, Nos2, Il6 and Il12, associated with pro-inflammatory mediators, and reduced expression of the anti-inflammatory Il10. Moreover, the adipose tissue of PAFRKO mice presented more pro-inflammatory macrophages, characterized by an increased frequency of F4/80(+)CD11c(+) cells. Blood monocytes of PAFRKO mice also exhibited a pro-inflammatory phenotype (increased frequency of Ly6C(+) cells) and PAFR ligands were detected in the serum of both PAFRKO and WT mice. Regarding metabolic parameters, compared with WT, PAFRKO mice had: (i) higher weight gain and serum glucose concentration levels; (ii) decreased insulin-stimulated glucose disappearance; (iii) insulin resistance in the liver; (iv) increased expression of Ldlr in the liver. In mice fed on an HFD, some of these changes were potentiated, particularly in the liver. Thus it seems that endogenous ligands of PAFR are responsible for maintaining the anti-inflammatory profile of blood monocytes and ATMs under physiological conditions. In the absence of

  10. Microglia phenotype diversity

    NARCIS (Netherlands)

    Olah, M.; Biber, K.; Vinet, J.; Boddeke, H. W. G. M.

    2011-01-01

    Microglia, the tissue macrophages of the brain, have under healthy conditions a resting phenotype that is characterized by a ramified morphology. With their fine processes microglia are continuously scanning their environment. Upon any homeostatic disturbance microglia rapidly change their phenotype

  11. Microglia phenotype diversity

    NARCIS (Netherlands)

    Olah, M.; Biber, K.; Vinet, J.; Boddeke, H. W. G. M.

    2011-01-01

    Microglia, the tissue macrophages of the brain, have under healthy conditions a resting phenotype that is characterized by a ramified morphology. With their fine processes microglia are continuously scanning their environment. Upon any homeostatic disturbance microglia rapidly change their phenotype

  12. Microglia phenotype diversity

    NARCIS (Netherlands)

    Olah, M.; Biber, K.; Vinet, J.; Boddeke, H. W. G. M.

    Microglia, the tissue macrophages of the brain, have under healthy conditions a resting phenotype that is characterized by a ramified morphology. With their fine processes microglia are continuously scanning their environment. Upon any homeostatic disturbance microglia rapidly change their phenotype

  13. Exploring the Lean Phenotype of Glutathione-Depleted Mice: Thiol, Amino Acid and Fatty Acid Profiles

    Science.gov (United States)

    Elshorbagy, Amany K.; Jernerén, Fredrik; Scudamore, Cheryl L.; McMurray, Fiona; Cater, Heather; Hough, Tertius; Cox, Roger; Refsum, Helga

    2016-01-01

    Background Although reduced glutathione (rGSH) is decreased in obese mice and humans, block of GSH synthesis by buthionine sulfoximine (BSO) results in a lean, insulin-sensitive phenotype. Data is lacking about the effect of BSO on GSH precursors, cysteine and glutamate. Plasma total cysteine (tCys) is positively associated with stearoyl-coenzyme A desaturase (SCD) activity and adiposity in humans and animal models. Objective To explore the phenotype, amino acid and fatty acid profiles in BSO-treated mice. Design Male C3H/HeH mice aged 11 weeks were fed a high-fat diet with or without BSO in drinking water (30 mmol/L) for 8 weeks. Amino acid and fatty acid changes were assessed, as well as food consumption, energy expenditure, locomotor activity, body composition and liver vacuolation (steatosis). Results Despite higher food intake, BSO decreased particularly fat mass but also lean mass (both P<0.001), and prevented fatty liver vacuolation. Physical activity increased during the dark phase. BSO decreased plasma free fatty acids and enhanced insulin sensitivity. BSO did not alter liver rGSH, but decreased plasma total GSH (tGSH) and rGSH (by ~70%), and liver tGSH (by 82%). Glutamate accumulated in plasma and liver. Urine excretion of cysteine and its precursors was increased by BSO. tCys, rCys and cystine decreased in plasma (by 23–45%, P<0.001 for all), but were maintained in liver, at the expense of decreased taurine. Free and total plasma concentrations of the SCD products, oleic and palmitoleic acids were decreased (by 27–38%, P <0.001 for all). Conclusion Counterintuitively, block of GSH synthesis decreases circulating tCys, raising the question of whether the BSO-induced obesity-resistance is linked to cysteine depletion. Cysteine-supplementation of BSO-treated mice is warranted to dissect the effects of cysteine and GSH depletion on energy metabolism. PMID:27788147

  14. Establishing Liver Bioreactors for In Vitro Research.

    Science.gov (United States)

    Rebelo, Sofia P; Costa, Rita; Sousa, Marcos F Q; Brito, Catarina; Alves, Paula M

    2015-01-01

    In vitro systems that can effectively model liver function for long periods of time are fundamental tools for preclinical research. Nevertheless, the adoption of in vitro research tools at the earliest stages of drug development has been hampered by the lack of culture systems that offer the robustness, scalability, and flexibility necessary to meet industry's demands. Bioreactor-based technologies, such as stirred tank bioreactors, constitute a feasible approach to aggregate hepatic cells and maintain long-term three-dimensional cultures. These three-dimensional cultures sustain the polarity, differentiated phenotype, and metabolic performance of human hepatocytes. Culture in computer-controlled stirred tank bioreactors allows the maintenance of physiological conditions, such as pH, dissolved oxygen, and temperature, with minimal fluctuations. Moreover, by operating in perfusion mode, gradients of soluble factors and metabolic by-products can be established, aiming at resembling the in vivo microenvironment. This chapter provides a protocol for the aggregation and culture of hepatocyte spheroids in stirred tank bioreactors by applying perfusion mode for the long-term culture of human hepatocytes. This in vitro culture system is compatible with feeding high-throughput screening platforms for the assessment of drug elimination pathways, being a useful tool for toxicology research and drug development in the preclinical phase.

  15. Bulkloading and Maintaining XML Documents

    NARCIS (Netherlands)

    Schmidt, A.R.; Kersten, M.L.

    2002-01-01

    The popularity of XML as a exchange and storage format brings about massive amounts of documents to be stored, maintained and analyzed -- a challenge that traditionally has been tackled with Database Management Systems (DBMS). To open up the content of XML documents to analysis with declarative quer

  16. Liver Wellness

    Science.gov (United States)

    ... can cause the liver to swell and not work well. Prevention: Hepatitis A vaccination is the best way to prevent HAV. Other ways to stop the spread of HAV are: • Always washing your hands with soap and warm water immediately after using the bathroom ...

  17. Liver Biopsy

    Science.gov (United States)

    ... and sends the sample to a lab for analysis. People with severe liver disease often have blood-clotting problems that can increase their chance of ... called collapsed lung, which occurs when air or gas builds up in the pleural space. ... of blood in the pleural space. puncture of other organs. ...

  18. Elevated Liver Enzymes

    Science.gov (United States)

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  19. Tests for Liver Cancer

    Science.gov (United States)

    ... Cancer Early Detection, Diagnosis, and Staging Tests for Liver Cancer If you have some of the signs ... Health Care Team About Liver Cancer? More In Liver Cancer About Liver Cancer Causes, Risk Factors, and ...

  20. Liver cancer - hepatocellular carcinoma

    Science.gov (United States)

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or ...

  1. Liver Transplant: Nutrition

    Science.gov (United States)

    ... ZIP code here Enter ZIP code here Liver Transplant: Nutrition for Veterans and the Public Nutrition Liver ... apply to transplant and liver disease patients. Pre-Transplant Protein Malnutrition -- Many patients with end stage liver ...

  2. Liver Function Tests

    Science.gov (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  3. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008075 Effect of Jiangzhi granules on expression of leptin receptor mRNA, P-JAK2 and P-STAT3 in rats with non-alcoholic fatty liver disease. MA Zansong(马赞颂), et al. Dept Gastroenterol, Instit Spleen and Stomach Dis, Longhua Hosp. Shanghai TCM Univ, Shanghai 200032.World Chin J Digestol 2007;15(32):3360-3366. Objective To study the effect of Jiangzhi granules on non-alcoholic fatty liver disease in rats, and on the expression of

  4. Voriconazole and the liver

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Voriconazole is an azole useful for the prophylaxis andthe treatment of aspergillosis and other fungal infectionsin immunosuppressed subjects, as those found in aplasiaafter aggressive polychemotherapy treatments, afterhematopoietic stem cell, liver or lung transplantation.Its administration in therapeutic doses lead to extremelyvaried serum levels from patient to patient and even tothe same patient. The explanations are varied nonlinearpharmacokinetics, certain patient-related factors,including genetic polymorphisms in the cytochrome P4502C19 gene, the kidney and liver function, simultaneousadministration with other drugs metabolised by the samecytochrome. It is recommended to maintain the serumconcentrations of voriconazole between 1.5 and 4 μg/mL.At lower values its efficacy decreases and at highervalues the risk of neurological toxicity increases. Evenat these concentrations it is not excluded the possibleappearance of a variety of toxic effects, including onthe liver, manifested by cholestasis, hepatocytolisis, ortheir combination. It is recommended to monitor theclinical and laboratory evolution of all patients treatedwith voriconazole, and of the serum levels of the drugof those who belong to risk groups, even if there is stillno consensus on this issue, given the lack of correlationbetween the serum level and the occurrence of adverseeffects in many patients.

  5. Phenotype of the taurine transporter knockout mouse.

    Science.gov (United States)

    Warskulat, Ulrich; Heller-Stilb, Birgit; Oermann, Evelyn; Zilles, Karl; Haas, Helmut; Lang, Florian; Häussinger, Dieter

    2007-01-01

    This chapter reports present knowledge on the properties of mice with disrupted gene coding for the taurine transporter (taut-/- mice). Study of those mice unraveled some of the roles of taurine and its membrane transport for the development and maintenance of normal organ functions and morphology. When compared with wild-type controls, taut-/- mice have decreased taurine levels in skeletal and heart muscle by about 98%, in brain, kidney, plasma, and retina by 80 to 90%, and in liver by about 70%. taut-/- mice exhibit a lower body mass as well as a strongly reduced exercise capacity compared with taut+/- and wild-type mice. Furthermore, taut-/- mice show a variety of pathological features, for example, subtle derangement of renal osmoregulation, changes in neuroreceptor expression, and loss of long-term potentiation in the striatum, and they develop clinically relevant age-dependent disorders, for example, visual, auditory, and olfactory dysfunctions, unspecific hepatitis, and liver fibrosis. Taurine-deficient animal models such as acutely dietary-manipulated foxes and cats, pharmacologically induced taurine-deficient rats, and taurine transporter knockout mouse are powerful tools allowing identification of the mechanisms and complexities of diseases mediated by impaired taurine transport and taurine depletion (Chapman et al., 1993; Heller-Stilb et al., 2002; Huxtable, 1992; Lake, 1993; Moise et al., 1991; Novotny et al., 1991; Pion et al., 1987; Timbrell et al., 1995; Warskulat et al., 2004, 2006b). Taurine, which is the most abundant amino acid in many tissues, is normally found in intracellular concentrations of 10 to 70 mmol/kg in mammalian heart, brain, skeletal muscle, liver, and retina (Chapman et al., 1993; Green et al., 1991; Huxable, 1992; Timbrell et al., 1995). These high taurine levels are maintained by an ubiquitous expression of Na(+)-dependent taurine transporter (TAUT) in the plasma membrane (Burg, 1995; Kwon and Handler, 1995; Lang et al., 1998

  6. The fatty liver dystrophy (fld) mutation: Developmentally related alterations in hepatic triglyceride metabolism and protein expression

    Energy Technology Data Exchange (ETDEWEB)

    Reue, K.; Rehnmark, S.; Cohen, R.D.; Leete, T.H.; Doolittle, M.H. [West Los Angeles VA Medical Center, CA (United States). Lipid Research Lab.]|[Univ. of California, Los Angeles, CA (United States). Dept. of Medicine; Giometti, C.S.; Mishler, K. [Argonne National Lab., IL (United States); Slavin, B.G. [Univ. of Southern California, Los Angeles, CA (United States)

    1997-07-01

    Fatty liver dystrophy (fld) is an autosomal recessive mutation in mice characterized by hypertriglyceridemia and development of a fatty liver in the early neonatal period. Also associated with the fld phenotype is a tissue-specific deficiency in the expression of lipoprotein lipase and hepatic lipase, as well as elevations in hepatic apolipoprotein A-IV and apolipoprotein C-II mRNA levels. Although these lipid abnormalities resolve at the age of weaning, adult mutant mice exhibit a peripheral neuropathy associated with abnormal myelin formation. The fatty liver in fld/fld neonates is characterized by the accumulation of large triglyceride droplets within the parenchymal cells, and these droplets persist within isolated hepatocytes maintained in culture for several days. To identify the metabolic defect that leads to lipid accumulation, the authors investigated several aspects of cellular triglyceride metabolism. The mutant mice exhibited normal activity of acid triacylglycerol lipase, an enzyme thought to be responsible for hydrolysis of dietary triglycerides in the liver. Metabolic labeling studies performed with oleic acid revealed that free fatty acids accumulate in the liver of 3 day old fld/fld mice, but not in adults. This accumulation in liver was mirrored by elevated free fatty acid levels in plasma of fld/fld neonates, with levels highest in very young mice and returning to normal by the age of one month. Quantitation of fatty acid oxidation in cells isolated from fld/fld neonates revealed that oxidation rate is reduced 60% in hepatocytes and 40% in fibroblasts; hepatocytes from adult fld/fld mice exhibited an oxidation rate similar to those from wild-type mice.

  7. Disturbance maintains alternative biome states.

    Science.gov (United States)

    Dantas, Vinícius de L; Hirota, Marina; Oliveira, Rafael S; Pausas, Juli G

    2016-01-01

    Understanding the mechanisms controlling the distribution of biomes remains a challenge. Although tropical biome distribution has traditionally been explained by climate and soil, contrasting vegetation types often occur as mosaics with sharp boundaries under very similar environmental conditions. While evidence suggests that these biomes are alternative states, empirical broad-scale support to this hypothesis is still lacking. Using community-level field data and a novel resource-niche overlap approach, we show that, for a wide range of environmental conditions, fire feedbacks maintain savannas and forests as alternative biome states in both the Neotropics and the Afrotropics. In addition, wooded grasslands and savannas occurred as alternative grassy states in the Afrotropics, depending on the relative importance of fire and herbivory feedbacks. These results are consistent with landscape scale evidence and suggest that disturbance is a general factor driving and maintaining alternative biome states and vegetation mosaics in the tropics.

  8. Single cell dynamic phenotyping

    OpenAIRE

    Katherin Patsch; Chi-Li Chiu; Mark Engeln; Agus, David B.; Parag Mallick; Shannon M. Mumenthaler; Daniel Ruderman

    2016-01-01

    Live cell imaging has improved our ability to measure phenotypic heterogeneity. However, bottlenecks in imaging and image processing often make it difficult to differentiate interesting biological behavior from technical artifact. Thus there is a need for new methods that improve data quality without sacrificing throughput. Here we present a 3-step workflow to improve dynamic phenotype measurements of heterogeneous cell populations. We provide guidelines for image acquisition, phenotype track...

  9. Disseminated breast cancer cells acquire a highly malignant and aggressive metastatic phenotype during metastatic latency in the bone.

    Directory of Open Access Journals (Sweden)

    Carolyn G Marsden

    Full Text Available BACKGROUND: Disseminated tumor cells (DTCs in the bone marrow may exist in a dormant state for extended periods of time, maintaining the ability to proliferate upon activation, engraft at new sites, and form detectable metastases. However, understanding of the behavior and biology of dormant breast cancer cells in the bone marrow niche remains limited, as well as their potential involvement in tumor recurrence and metastasis. Therefore, the purpose of this study was to investigate the tumorigenicity and metastatic potential of dormant disseminated breast cancer cells (prior to activation in the bone marrow. METHODOLOGY/PRINCIPAL FINDINGS: Total bone marrow, isolated from mice previously injected with tumorspheres into the mammary fat pad, was injected into the mammary fat pad of NUDE mice. As a negative control, bone marrow isolated from non-injected mice was injected into the mammary fat pad of NUDE mice. The resultant tumors were analyzed by immunohistochemistry for expression of epithelial and mesenchymal markers. Mouse lungs, livers, and kidneys were analyzed by H+E staining to detect metastases. The injection of bone marrow isolated from mice previously injected with tumorspheres into the mammary fat pad, resulted in large tumor formation in the mammary fat pad 2 months post-injection. However, the injection of bone marrow isolated from non-injected mice did not result in tumor formation in the mammary fat pad. The DTC-derived tumors exhibited accelerated development of metastatic lesions within the lung, liver and kidney. The resultant tumors and the majority of metastatic lesions within the lung and liver exhibited a mesenchymal-like phenotype. CONCLUSIONS/SIGNIFICANCE: Dormant DTCs within the bone marrow are highly malignant upon injection into the mammary fat pad, with the accelerated development of metastatic lesions within the lung, liver and kidney. These results suggest the acquisition of a more aggressive phenotype of DTCs during

  10. Research Progression of Cellular Autophagy in Liver System Diseases

    Directory of Open Access Journals (Sweden)

    Chunyun Liu

    2013-09-01

    Full Text Available Autophagy is a basic biological phenomenon widely existed in eukaryotic cells and an important mechanism for cells to adjust to the surrounding environment, prevent invasion of pathogenic micro-organisms and maintain homeostasis, whose activity changes evidently in multiple liver system diseases, suggesting that there is close association between autophagy and the generation and development of liver system diseases. It is also reported that autophagy develops and exerts an important function in many liver-related diseases, such as hepatic carcinoma, non-alcoholic fatty liver disease, alcoholic liver disease, viral liver disease and acute liver injury. Therefore, this study aimed to summarize the relationship between autophagy and multiple liver diseases, hoping to explore the effect of autophagy in liver system diseases and further study the regulative effect of autophagy so as to provide new thoughts for their treatment.

  11. Research Progression of Cellular Autophagy in Liver System Diseases

    Institute of Scientific and Technical Information of China (English)

    Liu Chunyun; Gong Xiangwen; Xiao Xinfa; Yuan Xiangying

    2013-01-01

    Autophagy is a basic biological phenomenon widely existed in eukaryotic cells and an important mechanism for cells to adjust to the surrounding environment, prevent invasion of pathogenic micro-organisms and maintain homeostasis, whose activity changes evidently in multiple liver system diseases, suggesting that there is close association between autophagy and the generation and development of liver system diseases. It is also reported that autophagy develops and exerts an important function in many liver-related diseases, such as hepatic carcinoma, non-alcoholic fatty liver disease, alcoholic liver disease, viral liver disease and acute liver injury. Therefore, this study aimed to summarize the relationship between autophagy and multiple liver diseases, hoping to explore the effect of autophagy in liver system diseases and further study the regulative effect of autophagy so as to provide new thoughts for their treatment.

  12. Iron deficiency alters megakaryopoiesis and platelet phenotype independent of thrombopoietin.

    Science.gov (United States)

    Evstatiev, Rayko; Bukaty, Adam; Jimenez, Kristine; Kulnigg-Dabsch, Stefanie; Surman, Lidia; Schmid, Werner; Eferl, Robert; Lippert, Kathrin; Scheiber-Mojdehkar, Barbara; Kvasnicka, Hans Michael; Khare, Vineeta; Gasche, Christoph

    2014-05-01

    Iron deficiency is a common cause of reactive thrombocytosis, however, the exact pathways have not been revealed. Here we aimed to study the mechanisms behind iron deficiency-induced thrombocytosis. Within few weeks, iron-depleted diet caused iron deficiency in young Sprague-Dawley rats, as reflected by a drop in hemoglobin, mean corpuscular volume, hepatic iron content and hepcidin mRNA in the liver. Thrombocytosis established in parallel. Moreover, platelets produced in iron deficient animals displayed a higher mean platelet volume and increased aggregation. Bone marrow studies revealed subtle alterations that are suggestive of expansion of megakaryocyte progenitors, an increase in megakaryocyte ploidy and accelerated megakaryocyte differentiation. Iron deficiency did not alter the production of hematopoietic growth factors such as thrombopoietin, interleukin 6 or interleukin 11. Megakaryocytic cell lines grown in iron-depleted conditions exhibited reduced proliferation but increased ploidy and cell size. Our data suggest that iron deficiency increases megakaryopoietic differentiation and alters platelet phenotype without changes in megakaryocyte growth factors, specifically TPO. Iron deficiency-induced thrombocytosis may have evolved to maintain or increase the coagulation capacity in conditions with chronic bleeding.

  13. Extrarenal phenotypes of the UT-B knockout mouse.

    Science.gov (United States)

    Yang, Baoxue; Li, Xin; Guo, Lirong; Meng, Yan; Dong, Zixun; Zhao, Xuejian

    2014-01-01

    The urea transporter UT-B is expressed in multiple tissues including erythrocytes, kidney, brain, heart, liver, colon, bone marrow, spleen, lung, skeletal muscle, bladder, prostate, and testis in mammals. Phenotype analysis of UT-B-null mice has confirmed that UT-B deletion results in a urea-selective urine-concentrating defect (see Chap. 9 ). The functional significance of UT-B in extrarenal tissues studied in the UT-B-null mouse is discussed in this chapter. UT-B-null mice present depression-like behavior with urea accumulation and nitric oxide reduction in the hippocampus. UT-B deletion causes a cardiac conduction defect, and TNNT2 and ANP expression changes in the aged UT-B-null heart. UT-B also plays a very important role in protecting bladder urothelium from DNA damage and apoptosis by regulating the urea concentration in urothelial cells. UT-B functional deficiency results in urea accumulation in the testis and early maturation of the male reproductive system. These results show that UT-B is an indispensable transporter involved in maintaining physiological functions in different tissues.

  14. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970345 An experimental and clinical study on α1-adrenergic receptor of liver plasma membranes in cir-rhosis with portal hypertension. ZHANG Youcheng(张有成), et al. Dept Surg, People’s Hosp, Beijing MedUniv, Beijing, 100044 Chin J Dig 1996; 16(6): 332-335.

  15. NMG documentation, part 3: maintainer`s guide

    Energy Technology Data Exchange (ETDEWEB)

    Fritsch, F.N.; Dickinson, R.P. Jr.

    1996-07-01

    This is the third of a three-part report documenting NMG, the Numerical Mathematics Guide. Part I is aimed at the user of the systenL It contains an introduction, with an out- line of the complete report, and Chapter 1, User`s Point of View. Part II is aimed at the programmer and contains Chapter 2, How It Works. Part III is aimed at the maintainer of NMG and contains Chapter 3, Maintenance, and Chapter 4, Validation. Because its contents are so specialized, Part III will receive only limited distribution. Note that each chapter has its own page numbering and table of contents.

  16. Functional validation of GWAS gene candidates for abnormal liver function during zebrafish liver development

    Directory of Open Access Journals (Sweden)

    Leah Y. Liu

    2013-09-01

    Genome-wide association studies (GWAS have revealed numerous associations between many phenotypes and gene candidates. Frequently, however, further elucidation of gene function has not been achieved. A recent GWAS identified 69 candidate genes associated with elevated liver enzyme concentrations, which are clinical markers of liver disease. To investigate the role of these genes in liver homeostasis, we narrowed down this list to 12 genes based on zebrafish orthology, zebrafish liver expression and disease correlation. To assess the function of gene candidates during liver development, we assayed hepatic progenitors at 48 hours post fertilization (hpf and hepatocytes at 72 hpf using in situ hybridization following morpholino knockdown in zebrafish embryos. Knockdown of three genes (pnpla3, pklr and mapk10 decreased expression of hepatic progenitor cells, whereas knockdown of eight genes (pnpla3, cpn1, trib1, fads2, slc2a2, pklr, mapk10 and samm50 decreased cell-specific hepatocyte expression. We then induced liver injury in zebrafish embryos using acetaminophen exposure and observed changes in liver toxicity incidence in morphants. Prioritization of GWAS candidates and morpholino knockdown expedites the study of newly identified genes impacting liver development and represents a feasible method for initial assessment of candidate genes to instruct further mechanistic analyses. Our analysis can be extended to GWAS for additional disease-associated phenotypes.

  17. Hepatic progenitors for liver disease: current position

    Directory of Open Access Journals (Sweden)

    Alice Conigliaro

    2010-02-01

    Full Text Available Alice Conigliaro1, David A Brenner2, Tatiana Kisseleva21University “La Sapienza”, Dipartimento di Biotecnologie Cellulari ed Ematologia Policlinico Umberto I, V Clinica Medica, Rome, Italy; 2Department of Medicine, University of California, San Diego, La Jolla, CA, USAAbstract: Liver regeneration restores the original functionality of hepatocytes and cholangiocytes in response to injury. It is regulated on several levels, with different cellular populations contributing to this process, eg, hepatocytes, liver precursor cells, intrahepatic stem cells. In response to injury, mature hepatocytes have the capability to proliferate and give rise to new hepatocytes and cholangiocytes. Meanwhile, liver precursor cells (oval cells have become the most recognized bipotential precursor cells in the damaged liver. They rapidly proliferate, change their cellular composition, and differentiate into hepatocytes and cholangiocytes to compensate for the cellular loss and maintain liver homeostasis. There is a growing body of evidence that oval cells originate from the intrahepatic stem cell(s, which in turn give(s rise to epithelial, including oval cells, and/or other hepatic cells of nonepithelial origin. Since there is a close relationship between the liver and hematopoiesis, bone marrow derived cells can also contribute to liver regeneration by the fusion of myeloid cells with damaged hepatocytes, or differentiation of mesenchymal stem cells into hepatocyte-like cells. The current review discusses the contribution of different cells to liver regeneration and their characteristics.Keywords: hepatic progenitor, liver disease, liver precursor cells, oval cells, hepatocytes, intrahepatic stem cells, cholangiocytes

  18. Alcoholic liver disease: the gut microbiome and liver cross talk.

    Science.gov (United States)

    Hartmann, Phillipp; Seebauer, Caroline T; Schnabl, Bernd

    2015-05-01

    Alcoholic liver disease (ALD) is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with ALD have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing the mucosal gut barrier, or preventing cellular responses to microbial products protect from experimental ALD. Therefore, intestinal dysbiosis and pathological bacterial translocation appear fundamental for the pathogenesis of ALD. This review highlights causes for intestinal dysbiosis and pathological bacterial translocation, their relationship, and consequences for ALD. We also discuss how the liver affects the intestinal microbiota.

  19. Association of alkaline phosphatase phenotypes with arthritides

    Directory of Open Access Journals (Sweden)

    Padmini A

    2004-01-01

    Full Text Available Arthritides, a symmetrical polyarticular disease of the bone are a heterogenous group of disorders in which hereditary and environmental factors in combination with an altered immune response appear to play a causative and pathogenic role in its occurrence. Alkaline phosphatase (ALP is an enzyme found in all tissues, with particularly high concentrations of ALP observed in the liver, bile ducts, placenta, and bone.Alkaline phosphatase is an orthophosphoric monoester phosphohydrolase catalyzing the hydrolysis of organic esters at alkaline pH, indicating that alkaline phosphatase is involved in fundamental biological processes.1 The present study envisages on identifying the specific electromorphic association of alkaline phosphatase with arthritides. Phenotyping of serum samples was carried out by PAGE (Polyacrylamide gel electrophoresis following Davies (19642 protocol on 41 juvenile arthritis, 150 rheumatoid arthritis and 100 osteo arthritis apart from, 25 normal children and 100 adult healthy subjects. Phenotyping of alkaline phosphatase revealed an increase in preponderance of p+ and p++ phenotypes in juvenile, rheumatoid and osteo arthritic patients. However a significant association of these phenotypes was observed only with rheumatoid arthritis condition (c2:17.46. Similarly, a significant increase of p+ phenotypes in female rheumatoid arthritis patients was observed (c2:14.973, suggesting that the decrease in p° (tissue non specific synthesis/secretion of alkaline phosphatase could be associated with decreased mineralization and ossification process in arthritis condition.

  20. Phenotype definition in epilepsy.

    Science.gov (United States)

    Winawer, Melodie R

    2006-05-01

    Phenotype definition consists of the use of epidemiologic, biological, molecular, or computational methods to systematically select features of a disorder that might result from distinct genetic influences. By carefully defining the target phenotype, or dividing the sample by phenotypic characteristics, we can hope to narrow the range of genes that influence risk for the trait in the study population, thereby increasing the likelihood of finding them. In this article, fundamental issues that arise in phenotyping in epilepsy and other disorders are reviewed, and factors complicating genotype-phenotype correlation are discussed. Methods of data collection, analysis, and interpretation are addressed, focusing on epidemiologic studies. With this foundation in place, the epilepsy subtypes and clinical features that appear to have a genetic basis are described, and the epidemiologic studies that have provided evidence for the heritability of these phenotypic characteristics, supporting their use in future genetic investigations, are reviewed. Finally, several molecular approaches to phenotype definition are discussed, in which the molecular defect, rather than the clinical phenotype, is used as a starting point.

  1. Control Inflation while Maintain Growth

    Institute of Scientific and Technical Information of China (English)

    Yang Junsheng

    2008-01-01

    @@ Dragged by the U.S.subprime crisis and the soaring oil price, the global economy is slowing down,causing problems to China, the country which has continuously achieved miraculous economic growth.Apart from the accumulation of high inflation and risks of overheated economy, China is attacked by serious natural disasters ever since the beginning of 2008,including the snow disaster, the earthquake and the flood.It is obviously that China's priority now is to bring inflation under control so as to maintain the stable growth of economy.

  2. Relationship between apolipoprotein E4 phenotype and postoperative cognitive dysfunction in patients with liver transplantation%肝移植患者载脂蛋白E4表型与术后认知功能障碍的关系

    Institute of Scientific and Technical Information of China (English)

    夏云飞; 颜涛; 周雅春; 李士通; 汪正平

    2012-01-01

    目的 探讨载脂蛋白E(ApoE)4表型与肝移植患者术后认知功能障碍(POCD)的关系.方法 选取50例肝移植患者,应用酶联免疫吸附试验定量测定患者术前的血清ApoE4和ApoE水平,根据ApoE4/ApoE的比值确定患者的ApoE表型,将其分为ApoE4组和非ApoE4组.术前、术后3和7d分别对患者进行简明精神状态量表(MMSE)评分.结果 共有40例患者完成术后随访,其中ApoE4组13例(32.5%).两组间年龄、性别构成、体重、术前总胆红素水平、术前肝功能分级(Child分级)、手术时间、无肝期时间、失血量、输血量(包括自体血)、补液量(晶体和胶体)的差异均无统计学意义(P值均>0.05).在术前,无肝期10、30、60 min,新肝期10、30 min及术毕,两组间平均动脉压、心率、中心静脉压、血红蛋白的差异均无统计学意义(P值均>0.05).术后3、7 d ApoE4组的MMSE评分分别为(26.0±2.O)和(25.6±2.3)分,非ApoE4组分别为(24.8±2.6)和(25.9±2.1)分,分别较同组术前的(29.0±0.7)和(28.5±0.8)分显著下降(P值均<0.05),但两组间的差异均无统计学意义(P值均>0.05).ApoE4组和非ApoE4组术后3d的POCD发生率分别为53.8%和62.9%,术后7d分别为46.2%和40.7%,差异均无统计学意义(P值均>0.05).结论 肝移植患者ApoE4表型与POCD的发生无关.%Objective To investigate the relationship between apolipoprotein E (ApoE) 4 phenotype and postoperative cognitive dysfunction (POCD) in the patients with liver transplantation. Methods Blood samples from 50 liver transplantation patients were obtained before induction of anesthesia to detect serum ApoE4 and ApoE concentrations by enzyme-linked immunosorbent assay (ELISA). ApoE phenotypes were identified according to the concentration ratio between ApoE4 and ApoE. Then the patients were divided into ApoE4 group and non-ApoE4 group, and evaluated with mini-mental state examination (MMSE) for cognitive function before induction of anesthesia

  3. Low-dose interleukin-2 promotes STAT-5 phosphorylation, Treg survival and CTLA-4-dependent function in autoimmune liver diseases.

    Science.gov (United States)

    Jeffery, H C; Jeffery, L E; Lutz, P; Corrigan, M; Webb, G J; Hirschfield, G M; Adams, D H; Oo, Y H

    2017-02-08

    CD4(+) CD25(high) CD127(low) forkhead box protein 3 (FoxP3(+) ) regulatory T cells (Treg ) are essential for the maintenance of peripheral tolerance. Impaired Treg function and an imbalance between effector and Tregs contribute to the pathogenesis of autoimmune diseases. We reported recently that the hepatic microenvironment is deficient in interleukin (IL)-2, a cytokine essential for Treg survival and function. Consequently, few liver-infiltrating Treg demonstrate signal transducer and activator of transcription-5 (STAT-5) phosphorylation. To establish the potential of IL-2 to enhance Treg therapy, we investigated the effects of very low dose Proleukin (VLDP) on the phosphorylation of STAT-5 and the subsequent survival and function of Treg and T effector cells from the blood and livers of patients with autoimmune liver diseases. VLDP, at less than 5 IU/ml, resulted in selective phosphorylation of STAT-5 in Treg but not effector T cells or natural killer cells and associated with increased expression of cytotoxic T lymphocyte antigen-4 (CTLA-4), FoxP3 and CD25 and the anti-apoptotic protein Bcl-2 in Treg with the greatest enhancement of regulatory phenotype in the effector memory Treg population. VLDP also maintained expression of the liver-homing chemokine receptor CXCR3. VLDP enhanced Treg function in a CTLA-4-dependent manner. These findings open new avenues for future VLDP cytokine therapy alone or in combination with clinical grade Treg in autoimmune liver diseases, as VLDP could not only enhance regulatory phenotype and functional property but also the survival of intrahepatic Treg .

  4. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930137 Effects of selective and non-selectiveβ-adrenoreceptor blockers on portal hemody-namics in patients with liver cirrhosis.HUANGTianwei(黄天卫),et al.1st Affili Hosp,DalianMed Coll.Chin J Digest 1992;12(3):145-147.Effects of selective(atenolol)and non-selec-tive(propranolol)β-adrenoreceptor blockerson portal hemodynamics in patients with livercirrhosis were measured by pulsed Doppler du-

  5. Natural Killer cells and liver fibrosis

    Directory of Open Access Journals (Sweden)

    Frank eFasbender

    2016-01-01

    Full Text Available In the 40 years since the discovery of Natural Killer (NK cells it has been well established that these innate lymphocytes are important for early and effective immune responses against transformed cells and infections with different pathogens. In addition to these classical functions of NK cells, we now know that they are part of a larger family of innate lymphoid cells and that they can even mediate memory-like responses. Additionally, tissue resident NK cells with distinct phenotypical and functional characteristics have been identified. Here we focus on the phenotype of different NK cell subpopulations that can be found in the liver and summarize the current knowledge about the functional role of these cells with a special emphasis on liver fibrosis. NK cell cytotoxicity can contribute to liver damage in different forms of liver disease. However, NK cells can limit liver fibrosis by killing hepatic stellate cell-derived myofibroblasts, which play a key role in this pathogenic process. Therefore, liver NK cells need to be tightly regulated in order to balance these beneficial and pathological effects.

  6. Diagnosis and management of polycystic liver disease.

    Science.gov (United States)

    Gevers, Tom J G; Drenth, Joost P H

    2013-02-01

    Polycystic liver disease (PLD) is arbitrarily defined as a liver that contains >20 cysts. The condition is associated with two genetically distinct diseases: as a primary phenotype in isolated polycystic liver disease (PCLD) and as an extrarenal manifestation in autosomal dominant polycystic kidney disease (ADPKD). Processes involved in hepatic cystogenesis include ductal plate malformation with concomitant abnormal fluid secretion, altered cell-matrix interaction and cholangiocyte hyperproliferation. PLD is usually a benign disease, but can cause debilitating abdominal symptoms in some patients. The main risk factors for growth of liver cysts are female sex, exogenous oestrogen use and multiple pregnancies. Ultrasonography is very useful for achieving a correct diagnosis of a polycystic liver and to differentiate between ADPKD and PCLD. Current radiological and surgical therapies for symptomatic patients include aspiration-sclerotherapy, fenestration, segmental hepatic resection and liver transplantation. Medical therapies that interact with regulatory mechanisms controlling expansion and growth of liver cysts are under investigation. Somatostatin analogues are promising; several clinical trials have shown that these drugs can reduce the volume of polycystic livers. The purpose of this Review is to provide an update on the diagnosis and management of PLD with a focus on literature published in the past 4 years.

  7. Maintaining consistency in distributed systems

    Science.gov (United States)

    Birman, Kenneth P.

    1991-01-01

    In systems designed as assemblies of independently developed components, concurrent access to data or data structures normally arises within individual programs, and is controlled using mutual exclusion constructs, such as semaphores and monitors. Where data is persistent and/or sets of operation are related to one another, transactions or linearizability may be more appropriate. Systems that incorporate cooperative styles of distributed execution often replicate or distribute data within groups of components. In these cases, group oriented consistency properties must be maintained, and tools based on the virtual synchrony execution model greatly simplify the task confronting an application developer. All three styles of distributed computing are likely to be seen in future systems - often, within the same application. This leads us to propose an integrated approach that permits applications that use virtual synchrony with concurrent objects that respect a linearizability constraint, and vice versa. Transactional subsystems are treated as a special case of linearizability.

  8. Liver in systemic disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Potential causes of abnormal liver function tests include viral hepatitis, alcohol intake, nonalcoholic fatty liver disease, autoimmune liver diseases, hereditary diseases, hepatobiliary malignancies or infection, gallstones and drug-induced liver injury. Moreover, the liver may be involved in systemic diseases that mainly affect other organs. Therefore, in patients without etiology of liver injury by screening serology and diagnostic imaging, but who have systemic diseases, the abnormal liver function test results might be caused by the systemic disease. In most of these patients, the systemic disease should be treated primarily. However, some patients with systemic disease and severe liver injury or fulminant hepatic failure require intensive treatments of the liver.

  9. Bioartificial liver systems: why, what, whither?

    Science.gov (United States)

    Gerlach, Jörg C; Zeilinger, Katrin; Patzer Ii, John F

    2008-07-01

    Acute liver disease is a life-threatening condition for which liver transplantation is the only recognized effective therapy. While etiology varies considerably, the clinical course of acute liver failure is common among the etiologies: encephalopathy progressing toward coma and multiple organ failure. Detoxification processes, such as molecular adsorbent recirculating system (MARS) and Prometheus, have had limited success in altering blood chemistries positively in clinical evaluations, but have not been shown to be clinically effective with regard to patient survival or other clinical outcomes in any Phase III prospective, randomized trial. Bioartificial liver systems, which use liver cells (hepatocytes) to provide metabolic support as well as detoxification, have shown promising results in early clinical evaluations, but again have not demonstrated clinical significance in any Phase III prospective, randomized trial. Cell transplantation therapy has had limited success but is not practicable for wide use owing to a lack of cells (whole-organ transplantation has priority). New approaches in regenerative medicine for treatment of liver disease need to be directed toward providing a functional cell source, expandable in large quantities, for use in various applications. To this end, a novel bioreactor design is described that closely mimics the native liver cell environment and is easily scaled from microscopic (<1 ml cells) to clinical ( approximately 600 ml cells) size, while maintaining the same local cell environment throughout the bioreactor. The bioreactor is used for study of primary liver cell isolates, liver-derived cell lines and stem/progenitor cells.

  10. Recommendations for using standardised phenotypes in genetic association studies

    Directory of Open Access Journals (Sweden)

    Naylor Melissa G

    2009-07-01

    Full Text Available Abstract Genetic association studies of complex traits often rely on standardised quantitative phenotypes, such as percentage of predicted forced expiratory volume and body mass index to measure an underlying trait of interest (eg lung function, obesity. These phenotypes are appealing because they provide an easy mechanism for comparing subjects, although such standardisations may not be the best way to control for confounders and other covariates. We recommend adjusting raw or standardised phenotypes within the study population via regression. We illustrate through simulation that optimal power in both population- and family-based association tests is attained by using the residuals from within-study adjustment as the complex trait phenotype. An application of family-based association analysis of forced expiratory volume in one second, and obesity in the Childhood Asthma Management Program data, illustrates that power is maintained or increased when adjusted phenotype residuals are used instead of typical standardised quantitative phenotypes.

  11. Phenotype-genotype correlations in patients with Wilson's disease.

    Science.gov (United States)

    Ferenci, Peter

    2014-05-01

    There is considerable phenotypic variation in Wilson's disease (WD). Some patients present with hepatic disease during the first decade of life and some with neurological degeneration in adolescence or adult life, with or without overt liver disease. Although the absence of neurologic disease in patients with liver disease in childhood or adolescence can be explained by the limited time exposure of the central nervous system to copper toxicity, it is surprising that late-onset neurologic WD can occur without any evidence of liver involvement. This huge variability in the clinical presentation of WD in general reflects our limited knowledge on the natural history of WD. Genetic association studies require the phenotype to be defined as accurately as possible.

  12. On the origin of the liver

    Science.gov (United States)

    Friedman, Joshua R.; Kaestner, Klaus H.

    2011-01-01

    While it has been well established that the fetal liver originates from foregut endoderm, the identity of the mechanisms that maintain liver mass under both basal and injury conditions remains controversial. Dramatically different models have been proposed based on the experimental design employed. In this issue of the JCI, Malato and colleagues report their elegant new model for genetic lineage tracing of mature mouse hepatocytes using an adenoassociated virus–driven Cre recombinase. They show convincingly that maintenance of liver mass during normal turnover or in response to mild injury is achieved by mature hepatocytes, rather than cholangiocytes or specialized progenitor cells, as has been suggested by others. PMID:22105167

  13. Novel 3D Culture Systems for Studies of Human Liver Function and Assessments of the Hepatotoxicity of Drugs and Drug Candidates.

    Science.gov (United States)

    Lauschke, Volker M; Hendriks, Delilah F G; Bell, Catherine C; Andersson, Tommy B; Ingelman-Sundberg, Magnus

    2016-12-19

    The liver is an organ with critical importance for drug treatment as the disposition and response to a given drug is often determined by its hepatic metabolism. Patient-specific factors can entail increased susceptibility to drug-induced liver injury, which constitutes a major risk for drug development programs causing attrition of promising drug candidates or costly withdrawals in postmarketing stages. Hitherto, mainly animal studies and 2D hepatocyte systems have been used for the examination of human drug metabolism and toxicity. Yet, these models are far from satisfactory due to extensive species differences and because hepatocytes in 2D cultures rapidly dedifferentiate resulting in the loss of their hepatic phenotype and functionality. With the increasing comprehension that 3D cell culture systems more accurately reflect in vivo physiology, in the recent decade more and more research has focused on the development and optimization of various 3D culture strategies in an attempt to preserve liver properties in vitro. In this contribution, we critically review these developments, which have resulted in an arsenal of different static and perfused 3D models. These systems include sandwich-cultured hepatocytes, spheroid culture platforms, and various microfluidic liver or multiorgan biochips. Importantly, in many of these models hepatocytes maintain their phenotype for prolonged times, which allows probing the potential of newly developed chemical entities to cause chronic hepatotoxicity. Moreover, some platforms permit the investigation of drug action in specific genetic backgrounds or diseased hepatocytes, thereby significantly expanding the repertoire of tools to detect drug-induced liver injuries. It is concluded that the development of 3D liver models has hitherto been fruitful and that systems are now at hand whose sensitivity and specificity in detecting hepatotoxicity are superior to those of classical 2D culture systems. For the future, we highlight the

  14. Liver transplant for cholestatic liver diseases.

    Science.gov (United States)

    Carrion, Andres F; Bhamidimarri, Kalyan Ram

    2013-05-01

    Cholestatic liver diseases include a group of diverse disorders with different epidemiology, pathophysiology, clinical course, and prognosis. Despite significant advances in the clinical care of patients with cholestatic liver diseases, liver transplant (LT) remains the only definitive therapy for end-stage liver disease, regardless of the underlying cause. As per the United Network for Organ Sharing database, the rate of cadaveric LT for cholestatic liver disease was 18% in 1991, 10% in 2000, and 7.8% in 2008. This review summarizes the available evidence on various common and rare cholestatic liver diseases, disease-specific issues, and pertinent aspects of LT.

  15. Microenvironment of liver regeneration in liver cancer.

    Science.gov (United States)

    Li, Han-Min; Ye, Zhi-Hua

    2017-07-01

    The occurrence and development of liver cancer are essentially the most serious outcomes of uncontrolled liver regeneration. The progression of liver cancer is inevitably related to the abnormal microenvironment of liver regeneration. The deterioration observed in the microenvironment of liver regeneration is a necessary condition for the occurrence, development and metastasis of cancer. Therefore, the use of a technique to prevent and treat liver cancer via changes in the microenvironment of liver regeneration is a novel strategy. This strategy would be an effective way to delay, prevent or even reverse cancer occurrence, development and metastasis through an improvement in the liver regeneration microenvironment along with the integrated regulation of multiple components, targets, levels, channels and time sequences. In addition, the treatment of "tonifying Shen (Kidney) to regulate liver regeneration and repair by affecting stem cells and their microenvironment" can regulate "the dynamic imbalance between the normal liver regeneration and the abnormal liver regeneration"; this would improve the microenvironment of liver regeneration, which is also a mechanism by which liver cancer may be prevented or treated.

  16. Extensive transcriptome analysis correlates the plasticity of Entamoeba histolytica pathogenesis to rapid phenotype changes depending on the environment

    Science.gov (United States)

    Weber, Christian; Koutero, Mikael; Dillies, Marie-Agnes; Varet, Hugo; Lopez-Camarillo, Cesar; Coppée, Jean Yves; Hon, Chung-Chau; Guillén, Nancy

    2016-01-01

    Amoebiasis is a human infectious disease due to the amoeba parasite Entamoeba histolytica. The disease appears in only 20% of the infections. Diversity in phenotypes may occur within the same infectious strain in the gut; for instance, parasites can be commensal (in the intestinal lumen) or pathogenic (inside the tissue). The degree of pathogenesis of clinical isolates varies greatly. These findings raise the hypothesis that genetic derivation may account for amoebic diverse phenotypes. The main goal of this study was to analyse gene expression changes of a single virulent amoebic strain in different environmental contexts where it exhibit different degrees of virulence, namely isolated from humans and maintained through animal liver passages, in contact with the human colon and short or prolonged in vitro culture. The study reveals major transcriptome changes in virulent parasites upon contact with human colon explants, including genes related to sugar metabolism, cytoskeleton rearrangement, stress responses and DNA repair. Furthermore, in long-term cultured parasites, drastic changes in gene expression for proteins with functions for proteasome and tRNA activities were found. Globally we conclude that rapid changes in gene expression rather than genetic derivation can sustain the invasive phenotype of a single virulent isolate of E. histolytica. PMID:27767091

  17. Pyogenic liver abscess

    Science.gov (United States)

    Liver abscess; Bacterial liver abscess ... There are many possible causes of liver abscesses, including: Abdominal infection, such as appendicitis , diverticulitis , or a perforated bowel Infection in the blood Infection of the bile draining tubes ...

  18. Liver Disease and IBD

    Science.gov (United States)

    ... Home > Resources > Liver Disease and IBD Go Back Liver Disease and IBD Email Print + Share Several complications ... be necessary to make the definitive diagnosis. FATTY LIVER DISEASE (HEPATCI STEATOSIS) This is the most common ...

  19. Liver Function Tests

    Science.gov (United States)

    ... food, store energy, and remove poisons. Liver function tests are blood tests that check to see how well your liver ... hepatitis and cirrhosis. You may have liver function tests as part of a regular checkup. Or you ...

  20. Software Code Maintainability : A Literature Review

    Directory of Open Access Journals (Sweden)

    Berna Seref

    2016-05-01

    Full Text Available Software Maintainability is one of the most important quality attributes. To increase quality of a software, to manage software more efficient and to decrease cost of the software, maintainability, maintainability estimation and maintainability evaluation models have been proposed. However, the practical use of these models in software engineering tools and practice remained little due to their limitations or threats to validity. In this paper, results of our Literature Review about maintainability models, maintainability metrics and maintainability estimation are presented. Aim of this paper is providing a baseline for further searches and serving the needs of developers and customers.

  1. Amebic liver abscess

    Science.gov (United States)

    Hepatic amebiasis; Extraintestinal amebiasis; Abscess - amebic liver ... Amebic liver abscess is caused by Entamoeba histolytica. This parasite causes amebiasis , an intestinal infection that is also called ...

  2. Liv and Lucky in Liverland. . . Color Us Healthy! A Workbook about Your Liver = Un Cuaderno de trabajo sobre tu higado.

    Science.gov (United States)

    1995

    This workbook/coloring book, on the liver and good health is designed for primary school students. The 21 line drawings illustrate different aspects of liver function, maintaining a healthy liver, and preventing liver disease. Each page is captioned in both English and Spanish. (ND)

  3. Liv and Lucky in Liverland. . . Color Us Healthy! A Workbook about Your Liver = Un Cuaderno de trabajo sobre tu higado.

    Science.gov (United States)

    1995

    This workbook/coloring book, on the liver and good health is designed for primary school students. The 21 line drawings illustrate different aspects of liver function, maintaining a healthy liver, and preventing liver disease. Each page is captioned in both English and Spanish. (ND)

  4. Getting a New Liver: Facts about Liver Transplants

    Science.gov (United States)

    ... 2002 December 2006 March 2012 Getting A New Liver Facts About Liver Transplants American Society of Transplantation 1120 Route 73, ... views of the Society. _________________________________________________________________ 1 Getting a New Liver Facts About Liver Transplants A liver transplant is ...

  5. Enhancement of liver regeneration and liver surgery

    NARCIS (Netherlands)

    Olthof, P.B.

    2017-01-01

    Liver regeneration allows surgical resection of up to 75% of the liver and enables curative treatment potential for patients with primary or secondary hepatic malignancies. Liver surgery is associated with substantial risks, reflected by considerable morbidity and mortality rates. Optimization of

  6. Silymarin Accelerates Liver Regeneration after Partial Hepatectomy

    Directory of Open Access Journals (Sweden)

    Jia-Ping Wu

    2015-01-01

    Full Text Available Partial hepatectomy (PHx is a liver regeneration physiological response induced to maintain homeostasis. Liver regeneration evolved presumably to protect wild animals from catastrophic liver loss caused by toxins or tissue injury. Silymarin (Sm ability to stimulate liver regeneration has been an object of curiosity for many years. Silymarin has been investigated for use as an antioxidant and anticarcinogen. However, its use as a supportive treatment for liver damage is elusive. In this study, we fed silymarin (Sm, 25 mg/kg to male Sprague-Dawley rats for 7 weeks. Surgical 2/3 PHx was then conducted on the rats at 6 hrs, 24 hrs, and 72 hrs. Western blot and RT-PCR were conducted to detect the cell cycle activities and silymarin effects on hepatic regeneration. The results showed that silymarin enhanced liver regeneration by accelerating the cell cycle in PHx liver. Silymarin led to increased G1 phase (cyclin D1/pRb, S phase (cyclin E/E2F, G2 phase (cyclin B, and M phase (cyclin A protein and mRNA at 6 hrs, 24 hrs, and 72 hrs PHx. HGF, TGFα, and TGFβ1 growth factor expressions were also enhanced. We suggest that silymarin plays a crucial role in accelerated liver regeneration after PHx.

  7. Deregulation of energy metabolism promotes antifibrotic effects in human hepatic stellate cells and prevents liver fibrosis in a mouse model.

    Science.gov (United States)

    Karthikeyan, Swathi; Potter, James J; Geschwind, Jean-Francois; Sur, Surojit; Hamilton, James P; Vogelstein, Bert; Kinzler, Kenneth W; Mezey, Esteban; Ganapathy-Kanniappan, Shanmugasundaram

    2016-01-15

    Liver fibrosis and cirrhosis result from uncontrolled secretion and accumulation of extracellular matrix (ECM) proteins by hepatic stellate cells (HSCs) that are activated by liver injury and inflammation. Despite the progress in understanding the biology liver fibrogenesis and the identification of potential targets for treating fibrosis, development of an effective therapy remains elusive. Since an uninterrupted supply of intracellular energy is critical for the activated-HSCs to maintain constant synthesis and secretion of ECM, we hypothesized that interfering with energy metabolism could affect ECM secretion. Here we report that a sublethal dose of the energy blocker, 3-bromopyruvate (3-BrPA) facilitates phenotypic alteration of activated LX-2 (a human hepatic stellate cell line), into a less-active form. This treatment-dependent reversal of activated-LX2 cells was evidenced by a reduction in α-smooth muscle actin (α-SMA) and collagen secretion, and an increase in activity of matrix metalloproteases. Mechanistically, 3-BrPA-dependent antifibrotic effects involved down-regulation of the mitochondrial metabolic enzyme, ATP5E, and up-regulation of glycolysis, as evident by elevated levels of lactate dehydrogenase, lactate production and its transporter, MCT4. Finally, the antifibrotic effects of 3-BrPA were validated in vivo in a mouse model of carbon tetrachloride-induced liver fibrosis. Results from histopathology & histochemical staining for collagen and α-SMA substantiated that 3-BrPA promotes antifibrotic effects in vivo. Taken together, our data indicate that sublethal, metronomic treatment with 3-BrPA blocks the progression of liver fibrosis suggesting its potential as a novel therapeutic for treating liver fibrosis.

  8. Maintaining quality in blood banking.

    Science.gov (United States)

    Harvey, E; Hewison, C; Nevalainen, D E; Lloyd, H L

    1995-03-01

    component will warrant redress. The degree of fault attributed to the producer will in part depend on whether they have met the best available standards at all stages in the preparation of the product. If a Transfusion Service can show that it's operation has external accreditation, particularly to an internationally recognised standard such as ISO 9000 and they can show that staff have been properly trained, that equipment is properly supplied and maintained and that the facility is appropriate to the work being carried out, then the liability that exists when something goes wrong will be reduced.(ABSTRACT TRUNCATED AT 400 WORDS)

  9. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930537 Preliminary report on portal hyperten-tion in liver cirrhosis treated by transjugular in-trahepatic portosystemic stent shunt(analysis of8 cases).XU Ke(徐克),et al.Dept Radiol,lst Hosp,China Med Univ,Shenyang,110001.Chin J Radiol 1993;25(5):294—297.Transjugular intrahepatic portosystemic stentshunt(TIPPS)was performed in 8 cases of livercirrhosis with portal hypertention.Moderate orsevere hemorrhage from gastroesophageal variceshad happened in all patients for 2~5 times beforTIPSS.The average pressure of portal veindropped from 3.80±0.50kPa to 2.58±0.26kPa.The diameter of the shunt established be-tween portal and hepatic veins was 10~12mm.Gastrointestinal bleeding and ascites were effec-

  10. Biolog phenotype microarrays.

    Science.gov (United States)

    Shea, April; Wolcott, Mark; Daefler, Simon; Rozak, David A

    2012-01-01

    Phenotype microarrays nicely complement traditional genomic, transcriptomic, and proteomic analysis by offering opportunities for researchers to ground microbial systems analysis and modeling in a broad yet quantitative assessment of the organism's physiological response to different metabolites and environments. Biolog phenotype assays achieve this by coupling tetrazolium dyes with minimally defined nutrients to measure the impact of hundreds of carbon, nitrogen, phosphorous, and sulfur sources on redox reactions that result from compound-induced effects on the electron transport chain. Over the years, we have used Biolog's reproducible and highly sensitive assays to distinguish closely related bacterial isolates, to understand their metabolic differences, and to model their metabolic behavior using flux balance analysis. This chapter describes Biolog phenotype microarray system components, reagents, and methods, particularly as they apply to bacterial identification, characterization, and metabolic analysis.

  11. Regulation of liver development: implications for liver biology across the lifespan.

    Science.gov (United States)

    Gruppuso, Philip A; Sanders, Jennifer A

    2016-04-01

    The liver serves a spectrum of essential metabolic and synthetic functions that are required for the transition from fetal to postnatal life. Processes essential to the attainment of adequate liver mass and function during fetal life include cell lineage specification early in development, enzymic and other functional modes of differentiation throughout gestation, and ongoing cell proliferation to achieve adequate liver mass. Available data in laboratory rodents indicate that the signaling networks governing these processes in the fetus differ from those that can sustain liver function and mass in the adult. More specifically, fetal hepatocytes may develop independent of key mitogenic signaling pathways, including those involving the Erk mitogen-activated protein kinases MAPK1/3 and the mechanistic target of rapamycin (mTOR). In addition, the fetal liver is subject to environmental influences that, through epigenetic mechanisms, can have sustained effects on function and, by extension, contribute to the developmental origin of adult metabolic disease. Finally, the mitogen-independent phenotype of rat fetal hepatocytes in late gestation makes these cells suitable for cell-based therapy of liver injury. In the aggregate, studies on the mechanisms governing fetal liver development have implications not only for the perinatal metabolic transition but also for the prevention and treatment of liver disorders throughout the lifespan.

  12. Role of liver progenitors in liver regeneration.

    Science.gov (United States)

    Best, Jan; Manka, Paul; Syn, Wing-Kin; Dollé, Laurent; van Grunsven, Leo A; Canbay, Ali

    2015-02-01

    During massive liver injury and hepatocyte loss, the intrinsic regenerative capacity of the liver by replication of resident hepatocytes is overwhelmed. Treatment of this condition depends on the cause of liver injury, though in many cases liver transplantation (LT) remains the only curative option. LT for end stage chronic and acute liver diseases is hampered by shortage of donor organs and requires immunosuppression. Hepatocyte transplantation is limited by yet unresolved technical difficulties. Since currently no treatment is available to facilitate liver regeneration directly, therapies involving the use of resident liver stem or progenitor cells (LPCs) or non-liver stem cells are coming to fore. LPCs are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. Non-liver stem cells include embryonic stem cells (ES cells) and mesenchymal stem cells (MSCs). In the first section, we aim to provide an overview of the role of putative cytokines, growth factors, mitogens and hormones in regulating LPC response and briefly discuss the prognostic value of the LPC response in clinical practice. In the latter section, we will highlight the role of other (non-liver) stem cells in transplantation and discuss advantages and disadvantages of ES cells, induced pluripotent stem cells (iPS), as well as MSCs.

  13. Molecular mechanisms controlling the phenotype and the EMT/MET dynamics of hepatocyte.

    Science.gov (United States)

    Cicchini, Carla; Amicone, Laura; Alonzi, Tonino; Marchetti, Alessandra; Mancone, Carmine; Tripodi, Marco

    2015-02-01

    The complex spatial and paracrine relationships between the various liver histotypes are essential for proper functioning of the hepatic parenchymal cells. Only within a correct tissue organization, in fact, they stably maintain their identity and differentiated phenotype. The loss of histotype identity, which invariably occurs in the primary hepatocytes in culture, or in vivo in particular pathological conditions (fibrosis and tumours), is mainly because of the phenomenon of epithelial-to-mesenchymal transition (EMT). The EMT process, that occurs in the many epithelial cells, appears to be driven by a number of general, non-tissue-specific, master transcriptional regulators. The reverse process, the mesenchymal-to-epithelial transition (MET), as yet much less characterized at a molecular level, restores specific epithelial identities, and thus must include tissue-specific master elements. In this review, we will summarize the so far unveiled events of EMT/MET occurring in liver cells. In particular, we will focus on hepatocyte and describe the pivotal role in the control of EMT/MET dynamics exerted by a tissue-specific molecular mini-circuitry. Recent evidence, indeed, highlighted as two transcriptional factors, the master gene of EMT Snail, and the master gene of hepatocyte differentiation HNF4α, exhorting a direct reciprocal repression, act as pivotal elements in determining opposite cellular outcomes. The different balances between these two master regulators, further integrated by specific microRNAs, in fact, were found responsible for the EMT/METs dynamics as well as for the preservation of both hepatocyte and stem/precursor cells identity and differentiation. Overall, these findings impact the maintenance of stem cells and differentiated cells both in in vivo EMT/MET physio-pathological processes as well as in culture. © 2014 The Authors. Liver International Published by John Wiley & Sons Ltd.

  14. Kidney transplantation after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Li-Yang Wu; Hang Liu; Wei Liu; Han Li; Xiao-Dong Zhang

    2016-01-01

    Kidney transplantation after liver transplanta-tion (KALT) offers longer survival and a better quality of life to liver transplantation recipients who develop chronic renal failure. This article aimed to discuss the efifcacy and safety of KALT compared with other treatments. The medical records of 5 patients who had undergone KALT were retrospectively studied, together with a literature review of studies. Three of them developed chronic renal failure after liver transplanta-tion because of calcineurin inhibitor (CNI)-induced neph-rotoxicity, while the others had lupus nephritis or non-CNI drug-induced nephrotoxicity. No mortality was observed in the 5 patients. Three KALT cases showed good prognoses, maintaining a normal serum creatinine level during entire follow-up period. Chronic rejection occurred in the other two patients, and a kidney graft was removed from one of them. Our data suggested that KALT is a good alternative to dialysis for liver transplantation recipients. The cases also indicate that KALT can be performed with good long-term survival.

  15. Wnt signaling in liver physiology and pathology

    Institute of Scientific and Technical Information of China (English)

    Satdarshan P. Singh Monga

    2009-01-01

    @@ 1 Wnt/β-catenin signaling This signaling pathway is known to play key roles during development and in maintaining homeostasis in many adult tissues. Its aberrant activation is associated with cancers in many tissues such as breast, colon, pancreas, skin and liver.

  16. Analysis of multiple invasive and non invasive therapeutic options for polycystic livers. Call for a Yielding Single Treatment Strategy.

    NARCIS (Netherlands)

    Keimpema, L. van

    2010-01-01

    This thesis describes studies on the treatment of polycystic livers. Polycystic livers are characterized by the presence of numerous cysts scattered throughout the whole liver parenchyma. This phenotype occurs in the setting of two inherited diseases: either in combination with polycystic kidneys:

  17. Hepatic HNF4α Is Essential for Maintaining Triglyceride and Cholesterol Homeostasis

    Science.gov (United States)

    Yin, Liya; Ma, Huiyan; Ge, Xuemei; Edwards, Peter A.; Zhang, Yanqiao

    2010-01-01

    Objective Loss-of-function mutations in human hepatocyte nuclear factor 4α (HNF4α) are associated with maturity-onset diabetes of the young and lipid disorders. However, the mechanisms underlying the lipid disorders are poorly understood. In this report, we determined the effect of acute loss or augmentation of hepatic HNF4α function on lipid homeostasis. Methods and Results We generated adenovirus expressing LacZ (Ad-shLacZ) or small hairpin RNA of Hnf4α (Ad-shHnf4α). Tail vain injection of C57BL/6J mice with Ad-shHnf4α reduced hepatic Hnf4α expression and resulted in striking phenotypes including the development of fatty liver and a >80% decrease in plasma levels of triglycerides, total cholesterol and HDL-C. These latter changes were associated with reduced hepatic lipogenesis and impaired VLDL secretion. Deficiency in hepatic Hnf4α did not affect intestinal cholesterol absorption despite decreased expression of genes involved in bile acid synthesis. Consistent with the loss-of-function data, over-expression of Hnf4α induced numerous genes involved in lipid metabolism in isolated primary hepatocytes. Interestingly, many of these HNF4α-regulated genes were not induced in wild-type mice that over-expressed hepatic Hnf4α. Due to selective gene regulation, mice over-expressing hepatic Hnf4α had unchanged plasma triglyceride levels and decreased plasma cholesterol levels. Conclusions Loss of hepatic HNF4α results in severe lipid disorder as a result of dysregulation of multiple genes involved in lipid metabolism. In contrast, augmentation of hepatic HNF4α activity lowers plasma cholesterol levels but has no effect on plasma triglyceride levels due to selective gene regulation. Our data indicate that hepatic HNF4α is essential for controlling the basal expression of numerous genes involved in lipid metabolism and is indispensable for maintaining normal lipid homeostasis. PMID:21071704

  18. Association of Nonalcoholic Fatty Liver Disease with Hypertriglyceridaemic Wasit Phenotype Complicated with Type 2 Diabetes Mellitus%2型糖尿病合并高甘油三酯血症-腰围表型与非酒精性脂肪性肝病的相关性研究

    Institute of Scientific and Technical Information of China (English)

    丁炜光

    2014-01-01

    Objective To investigate the association of nonalcoholic fatty liver disease with hypertriglyceridaemic wasit phenotype complicated with type 2 diabetes mellitus. Methods Base on whether plasma triglycerides concentra⁃ tion≥1.7 mmol/L or not, waist circumference≥90 cm or not in men or≥85 cm or not in women, patients with type 2 diabe⁃tes mellitus (n=804) were divided into four groups:normal waist circumference with normal triglycerides, normal waist cir⁃cumference with hypertriglyceridemia, abdominal obesity with normal triglycerides and hypertriglyceridemic-waist pheno⁃type (HTWC). The four groups’clinical data were recorded. Body mass index (BMI), homeostasis model assessment insulin resistance (HOMA-IR) and nonalcoholic fatty liver disease fibrosis score (NAFLDFS) were calculated and the results were compared among four groups. Results BMI, waist circumference, systolic blood pressure, diastolic blood pressure, HOMA-IR, alanine aminotransferase, aspartate aminotransferase , γ-glutamyltransferase, serum uric acid,NAFLDFS and the inci⁃dence of NAFLD were all higher in the HTWC group compared to non-HTWC group (P<0.01). Logistic regression analysis revealed that besides BMI,γ-glutamyltransferase and serum uric acid,HTWC was also a risk factor for NAFLD in patients with type 2 diabetes mellitus(OR=1.986,95%CI:1.006-3.921). Conclusion HTWC is a risk factor for NAFLD in patients with type 2 diabetes mellitus. Screening and diagnosis of HTWC is helpful for reducing the occurrence of NAFLD and can slow its progress through controlling and interfering metabolic disturbance.%目的:探讨2型糖尿病(T2DM)合并高甘油三酯血症-腰围表型(HTWC)与非酒精性脂肪性肝病(NAFLD)之间的关系。方法选取T2DM患者804例,以血三酰甘油≥1.7 mmol/L、腰围男性≥90 cm或女性≥85 cm为切点,分为三酰甘油和腰围正常组、单纯高甘油三酯血症组、单纯腹型肥胖组、HTWC组。记录4组患者的

  19. 人参皂苷Rg1对非酒精性脂肪肝病大鼠脂肪酸β-氧化的改善作用研究%Study on the improvement effect of Ginsenoside Rg1 on nonalcoholic fatty liver phenotype by regulation ofβ-oxidation

    Institute of Scientific and Technical Information of China (English)

    廖文云; 徐丹

    2016-01-01

    Objective To investigate the role of Ginsenosides Rg1 for non-alcoholic fatty liver disease by β-oxidation.Methods 120 SD rats were randomly divided into control group(CON),model group(HFD),Ginsenosides Rg1low,medium and high dose group (GLD ,GMD and GHD) ,sodium deoxycholate of bear treatment group (PDT ) ,20 rats in each group .After 4 and 8 weeks treatment ,the rats were sacrificed ,Pathology of hepatic tissue was tested by HE staining ,and liver function ,lipid levels ,hepatic ac-yl-CoA synthetase (CoASH1) ,carnitine acyl transferase I(CATI) and acetyl coenzyme A oxidase 1 (ACOX1) mRNA and protein expression were tested .Results After 4 weeks of treatment ,the liver function tested by HE staining only improved in GHD group . After 8 weeks ,there′s a little fat particles aggregation in PDT and GLD groups ,but no infiltration of fat in GMD and GHD groups . After 4 weeks ,AST ,ALT and AKP ,CHOL ,TG and LDL-C levels were significantly lower in PDT ,GLD ,GMD and GHD groups compared with HFD group (P<0 .05) ,which were significant declined 8 weeks later .After 4 weeks ,HDL-C level in four groups was significantly increased ,then reached the normal level 8 weeks later .After 4 weeks ,CoASH1 ,CATI and ACOX1 expressions in hepatic tissue of four groups were significantly increased ,which improved more obviously after eight weeks .Conclusion Ginsen-oside Rg1 can improves nonalcoholic fatty liver phenotype by regulation of β-oxidation .%目的:研究人参皂苷Rg1对非酒精性脂肪肝病(NAFLD)大鼠β-氧化的作用。方法将120只SD大鼠分为对照组(CON组)、模型组(HFD组)及人参皂苷Rg1低、中、高剂量组(GLD、GMD、GHD组)和熊去氧胆酸钠治疗组(PDT组),每组20只,分别于治疗4、8周后处死大鼠各半,肝脏切片 HE染色,检测肝功能、血脂、肝脏脂酰CoA合成酶1(CoASH1)、脂酰肉毒碱转移酶I(CATI)及酰基辅酶A氧化酶1(ACOX1) mRNA和蛋白表达。结果治疗4

  20. Fibronectin Extra Domain A Promotes Liver Sinusoid Repair following Hepatectomy

    Science.gov (United States)

    Sackey-Aboagye, Bridget; Olsen, Abby L.; Mukherjee, Sarmistha M.; Ventriglia, Alexander; Yokosaki, Yasuyuki; Greenbaum, Linda E.; Lee, Gi Yun; Naga, Hani

    2016-01-01

    Liver sinusoidal endothelial cells (LSECs) are the main endothelial cells in the liver and are important for maintaining liver homeostasis as well as responding to injury. LSECs express cellular fibronectin containing the alternatively spliced extra domain A (EIIIA-cFN) and increase expression of this isoform after liver injury, although its function is not well understood. Here, we examined the role of EIIIA-cFN in liver regeneration following partial hepatectomy. We carried out two-thirds partial hepatectomies in mice lacking EIIIA-cFN and in their wild type littermates, studied liver endothelial cell adhesion on decellularized, EIIIA-cFN-containing matrices and investigated the role of cellular fibronectins in liver endothelial cell tubulogenesis. We found that liver weight recovery following hepatectomy was significantly delayed and that sinusoidal repair was impaired in EIIIA-cFN null mice, especially females, as was the lipid accumulation typical of the post-hepatectomy liver. In vitro, we found that liver endothelial cells were more adhesive to cell-deposited matrices containing the EIIIA domain and that cellular fibronectin enhanced tubulogenesis and vascular cord formation. The integrin α9β1, which specifically binds EIIIA-cFN, promoted tubulogenesis and adhesion of liver endothelial cells to EIIIA-cFN. Our findings identify a role for EIIIA-cFN in liver regeneration and tubulogenesis. We suggest that sinusoidal repair is enhanced by increased LSEC adhesion, which is mediated by EIIIA-cFN. PMID:27741254

  1. Hemostatic disorders in orthotopic and auxiliary liver transplantation : clinical and experimental studies

    NARCIS (Netherlands)

    R.J. Porte (Robert)

    1989-01-01

    textabstractIn patients with severe liver disease, hepatic dysfunction may deteriorate to such an extent that conservative medical treatments are no longer sufficient to maintain the, for life essential, liver functions. For these patients the transplantation of a donor liver represents the only hop

  2. Immune mediated liver failure

    OpenAIRE

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capac...

  3. Appropriateness of Liver Biopsy

    OpenAIRE

    Thierry Poynard; Vlad Ratziu; Pierre Bedossa

    2000-01-01

    This review aims to discuss the appropriateness of liver biopsy in two frequent liver diseases, hepatitis C and alcoholic liver disease. The medical literature, published between 1965 and 1999, was reviewed by using MEDLINE. Only 0.1% of the publications were devoted specifically to the appropriateness of liver biopsy. Not all studies observed a significant agreement among doctors on the decision to use liver biopsy. Therefore, there is a possibility that hepatologists have significant, heter...

  4. The DFNA10 phenotype.

    NARCIS (Netherlands)

    Leenheer, E. de; Huygen, P.L.M.; Wayne, S.; Smith, R.J.H.; Cremers, C.W.R.J.

    2001-01-01

    We present a detailed analysis of the DFNA10 phenotype based on data from 25 hearing-impaired persons coming from a large American pedigree segregating for deafness at the DFNA10 locus (chromosome 6q22.3-23.2). Cross-sectional analysis of air conduction threshold-on-age data from all available last-

  5. Mixed phenotype acute leukemia

    Institute of Scientific and Technical Information of China (English)

    Ye Zixing; Wang Shujie

    2014-01-01

    Objective To highlight the current understanding of mixed phenotype acute leukemia (MPAL).Data sources We collected the relevant articles in PubMed (from 1985 to present),using the terms "mixed phenotype acute leukemia","hybrid acute leukemia","biphenotypic acute leukemia",and "mixed lineage leukemia".We also collected the relevant studies in WanFang Data base (from 2000 to present),using the terms "mixed phenotype acute leukemia" and "hybrid acute leukemia".Study selection We included all relevant studies concerning mixed phenotype acute leukemia in English and Chinese version,with no limitation of research design.The duplicated articles are excluded.Results MPAL is a rare subgroup of acute leukemia which expresses the myeloid and lymphoid markers simultaneously.The clinical manifestations of MPAL are similar to other acute leukemias.The World Health Organization classification and the European Group for Immunological classification of Leukaemias 1998 cdteria are most widely used.MPAL does not have a standard therapy regimen.Its treatment depends mostly on the patient's unique immunophenotypic and cytogenetic features,and also the experience of individual physician.The lack of effective treatment contributes to an undesirable prognosis.Conclusion Our understanding about MPAL is still limited.The diagnostic criteria have not been unified.The treatment of MPAL remains to be investigated.The prognostic factor is largely unclear yet.A better diagnostic cdteria and targeted therapeutics will improve the therapy effect and a subsequently better prognosis.

  6. COPD: Definition and Phenotypes

    DEFF Research Database (Denmark)

    Vestbo, J.

    2014-01-01

    particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. The evolution of this definition and the diagnostic criteria currently in use are discussed. COPD is increasingly divided in subgroups or phenotypes based on specific features and association...

  7. Obesity, fatty liver and liver cancer.

    Science.gov (United States)

    Qian, Yan; Fan, Jian-Gao

    2005-05-01

    It has been suggested that obesity and fatty liver may be associated with the morbidity and mortality of liver cancer, and the early diagnosis and effective treatment of fatty liver coupled with liver cancer are supposed to improve the prognosis of obese patients. This review was attempted to understand the relationship between obesity, fatty liver and liver cancer. An English-language literature search using PUBMED (1990-2004) on obesity, fatty liver and liver cancer and other related articles in Chinese. Obesity is associated with the risk of death from all cancers and from cancers at individual sites including liver cancer, and it is an independent risk factor for hepatocellular carcinoma (HCC) in patients with alcoholic cirrhosis and cryptogenic cirrhosis. Because nonalcoholic steatohepatitis has been implicated as a major cause of cryptogenic cirrhosis, the development of HCC may be part of progressive nature of this condition. Obesity is associated with the incidence and mortality of HCC. More frequent surveillance for HCC may be warranted in obese patients with fatty liver and attempts should be made to interrupt the progression from simple hepatic steatosis to steatohepatitis, cirrhosis and ultimately HCC.

  8. A new noninvasive technique for estimating hepatic triglyceride: will liver biopsy become redundant in diagnosing non-alcoholic fatty liver disease?

    NARCIS (Netherlands)

    Betzel, B.; Drenth, J.P.H.

    2014-01-01

    Obesity and metabolic syndrome are healthcare problems that continue to rise in frequency worldwide. Both phenotypes are a strong predictor for development of liver steatosis in the context of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. Ultrasound may detect steatosis, but it

  9. A new noninvasive technique for estimating hepatic triglyceride: will liver biopsy become redundant in diagnosing non-alcoholic fatty liver disease?

    NARCIS (Netherlands)

    Betzel, B.; Drenth, J.P.H.

    2014-01-01

    Obesity and metabolic syndrome are healthcare problems that continue to rise in frequency worldwide. Both phenotypes are a strong predictor for development of liver steatosis in the context of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. Ultrasound may detect steatosis, but

  10. Heterogeneity of liver cancer and personalized therapy.

    Science.gov (United States)

    Li, Liang; Wang, Hongyang

    2016-09-01

    Liver cancer is an extraordinarily heterogeneous malignant disease among the tumors that have so far been identified. Hepatocellular carcinoma (HCC) arises most frequently in the setting of chronic liver inflammation and fibrosis, and takes a variety of course in individual patients to process to tumor. The risk factors such as HBV and/or HCV infections, aflatoxin infection, abuse alcohol intake, metabolic syndrome, obesity and diabetes are closely related to the environmental and genetic susceptibilities to HCC. The consequent resulting genomic instability, molecular and signal transduction network disorders and microenvironmental discrepancies are characterized by the extraordinary heterogeneity of liver cancer. The histology-based definition of the morphological heterogeneity of liver cancer has been modified and refined to treat patients with targeted therapies, but this still cannot solve all the problems. Lack of consistent outcome for anticancer agents and conventional therapies in liver cancer treatment calls for assessing the benefits of new molecularly targeted drugs and combined therapy, under the heterogeneity condition of tumor. The present review article will provide the complex mechanism and phenotype of liver cancer heterogeneity, and help us to execute precision medicine in a really personalized manner.

  11. Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Ursula; M; Gehling; Marc; Willems; Kathleen; Schlagner; Ralf; A; Benndorf; Maura; Dandri; Jrg; Petersen; Martina; Sterneck; Joerg-Matthias; Pollok; Dieter; K; Hossfeld; Xavier; Rogiers

    2010-01-01

    AIM:To test the hypothesis that liver cirrhosis is associated with mobilization of hematopoietic progenitor cells. METHODS:Peripheral blood samples from 72 patients with liver cirrhosis of varying etiology were analyzed by flow cytometry.Identified progenitor cell subsets were immunoselected and used for functional assays in vitro. Plasma levels of stromal cell-derived factor-1(SDF-1) were measured using an enzyme linked immunosorbent assay.RESULTS:Progenitor cells with a CD133 + /CD45 + CD14 + phenotype we...

  12. Boy with autosomal recessive polycystic kidney and autosomal dominant polycystic liver disease.

    NARCIS (Netherlands)

    Zingg-Schenk, A.; Caduff, J.; Azzarello-Burri, S.; Bergmann, C.; Drenth, J.P.H.; Neuhaus, T.J.

    2012-01-01

    BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) shows a great phenotypic variability between patients, ranging from perinatal demise to mildly affected adults. Autosomal dominant polycystic liver disease (PCLD) does not manifest in childhood. CASE-DIAGNOSIS/TREATMENT: A boy was

  13. O-GlcNAc: a bittersweet switch in liver

    Directory of Open Access Journals (Sweden)

    Kaisi eZhang

    2014-12-01

    Full Text Available The liver is a vital organ responsible for maintaining nutrient homeostasis. After a meal, insulin stimulates glycogen and lipid synthesis in the liver; in the fasted state, glucagon induces gluconeogenesis and ketogenesis, which produce glucose and ketone bodies for other tissues to use as energy sources. These metabolic changes involve spatiotemporally coordinated signaling cascades. O-linked β-N-acetylglucosamine (O-GlcNAc modification has been recognized as a nutrient sensor and regulatory molecular switch. This review highlights mechanistic insights into spatiotemporal regulation of liver metabolism by O-GlcNAc modification and discusses its pathophysiological implications in insulin resistance, non-alcoholic fatty liver disease, and fibrosis.

  14. Stem cell-derived hepatocytes for functional liver replacement

    Directory of Open Access Journals (Sweden)

    Bruno eChrist

    2012-06-01

    Full Text Available Mesenchymal stem cells (MSC represent an alternate cell source to substitute for primary hepatocytes in hepatocyte transplantation because of their multiple differentiation potential and nearly unlimited availability. They may differentiate into hepatocyte-like cells in vitro and maintain specific hepatocyte functions also after transplantation into the regenerating livers of mice or rats both under injury and non-injury conditions. Depending on the underlying liver disease their mode of action is either to replace the diseased liver tissue or to support liver regeneration through their anti-inflammatory and anti-apoptotic as well as their pro-proliferative action.

  15. Stability is maintained in adults with Gaucher disease type 1 switched from velaglucerase alfa to eliglustat or imiglucerase: A sub-analysis of the eliglustat ENCORE trial.

    Science.gov (United States)

    Pleat, Rebecca; Cox, Timothy M; Burrow, T Andrew; Giraldo, Pilar; Goker-Alpan, Ozlem; Rosenbloom, Barry E; Croal, Laura R; Underhill, Lisa H; Gaemers, Sebastiaan J M; Peterschmitt, M Judith

    2016-12-01

    Gaucher disease type 1 is an autosomal recessive disorder caused by deficient activity of the lysosomal enzyme acid β-glucosidase resulting in accumulation of glucosylceramide and clinical manifestations of anemia, thrombocytopenia, hepatosplenomegaly, and skeletal disease. The historic standard of care is intravenous recombinant enzyme therapy with imiglucerase. Eliglustat, an oral substrate reduction therapy, is a first-line treatment for adults with Gaucher disease type 1 who have a compatible CYP2D6-metabolizer phenotype (≈ 95% of patients). The 12-month ENCORE trial (NCT00943111) found eliglustat non-inferior to imiglucerase in maintaining stability in adult Gaucher patients previously stabilized after ≥ 3 years of enzyme therapy (imiglucerase or velaglucerase alfa). This post-hoc analysis examined safety and efficacy in the 30 ENCORE patients who were receiving velaglucerase alfa at study entry and were randomized to eliglustat (n = 22) or imiglucerase (n = 8). Efficacy and safety in velaglucerase alfa-transitioned patients were consistent with the full ENCORE trial population; 90% of patients switched to eliglustat and 88% of patients switched to imiglucerase met the composite endpoint (stable hemoglobin concentration, platelet count, spleen volume, and liver volume). Clinical stability was maintained for 12 months in Gaucher disease type 1 patients in the ENCORE trial who switched from velaglucerase alfa to either eliglustat or imiglucerase.

  16. A “Forward Genomics” Approach Links Genotype to Phenotype using Independent Phenotypic Losses among Related Species

    Directory of Open Access Journals (Sweden)

    Michael Hiller

    2012-10-01

    Full Text Available Genotype-phenotype mapping is hampered by countless genomic changes between species. We introduce a computational “forward genomics” strategy that—given only an independently lost phenotype and whole genomes—matches genomic and phenotypic loss patterns to associate specific genomic regions with this phenotype. We conducted genome-wide screens for two metabolic phenotypes. First, our approach correctly matches the inactivated Gulo gene exactly with the species that lost the ability to synthesize vitamin C. Second, we attribute naturally low biliary phospholipid levels in guinea pigs and horses to the inactivated phospholipid transporter Abcb4. Human ABCB4 mutations also result in low phospholipid levels but lead to severe liver disease, suggesting compensatory mechanisms in guinea pig and horse. Our simulation studies, counts of independent changes in existing phenotype surveys, and the forthcoming availability of many new genomes all suggest that forward genomics can be applied to many phenotypes, including those relevant for human evolution and disease.

  17. Advances in Engineered Liver Models for Investigating Drug-Induced Liver Injury

    Science.gov (United States)

    Lin, Christine

    2016-01-01

    Drug-induced liver injury (DILI) is a major cause of drug attrition. Testing drugs on human liver models is essential to mitigate the risk of clinical DILI since animal studies do not always suffice due to species-specific differences in liver pathways. While primary human hepatocytes (PHHs) can be cultured on extracellular matrix proteins, a rapid decline in functions leads to low sensitivity (<50%) in DILI prediction. Semiconductor-driven engineering tools now allow precise control over the hepatocyte microenvironment to enhance and stabilize phenotypic functions. The latest platforms coculture PHHs with stromal cells to achieve hepatic stability and enable crosstalk between the various liver cell types towards capturing complex cellular mechanisms in DILI. The recent introduction of induced pluripotent stem cell-derived human hepatocyte-like cells can potentially allow a better understanding of interindividual differences in idiosyncratic DILI. Liver models are also being coupled to other tissue models via microfluidic perfusion to study the intertissue crosstalk upon drug exposure as in a live organism. Here, we review the major advances being made in the engineering of liver models and readouts as they pertain to DILI investigations. We anticipate that engineered human liver models will reduce drug attrition, animal usage, and cases of DILI in humans. PMID:27725933

  18. Biomarkers for liver fibrosis

    Science.gov (United States)

    Jacobs, Jon M.; Burnum-Johnson, Kristin E.; Baker, Erin M.; Smith, Richard D.; Gritsenko, Marina A.; Orton, Daniel

    2015-09-15

    Methods and systems for diagnosing or prognosing liver fibrosis in a subject are provided. In some examples, such methods and systems can include detecting liver fibrosis-related molecules in a sample obtained from the subject, comparing expression of the molecules in the sample to controls representing expression values expected in a subject who does not have liver fibrosis or who has non-progressing fibrosis, and diagnosing or prognosing liver fibrosis in the subject when differential expression of the molecules between the sample and the controls is detected. Kits for the diagnosis or prognosis of liver fibrosis in a subject are also provided which include reagents for detecting liver fibrosis related molecules.

  19. Biomarkers for liver fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, Jon M.; Burnum-Johnson, Kristin E.; Baker, Erin M.; Smith, Richard D.; Gritsenko, Marina A.; Orton, Daniel

    2017-05-16

    Methods and systems for diagnosing or prognosing liver fibrosis in a subject are provided. In some examples, such methods and systems can include detecting liver fibrosis-related molecules in a sample obtained from the subject, comparing expression of the molecules in the sample to controls representing expression values expected in a subject who does not have liver fibrosis or who has non-progressing fibrosis, and diagnosing or prognosing liver fibrosis in the subject when differential expression of the molecules between the sample and the controls is detected. Kits for the diagnosis or prognosis of liver fibrosis in a subject are also provided which include reagents for detecting liver fibrosis related molecules.

  20. Modifying factors and phenotypic diversity in Wilson's disease.

    Science.gov (United States)

    Lutsenko, Svetlana

    2014-05-01

    Wilson's disease (WD) is a human disorder of copper homeostasis caused by mutations in the copper-transporting ATPase ATP7B. WD is characterized by copper accumulation, predominantly in the liver and brain, hepatic pathology, and wide differences between patients in the age of onset and the spectrum of symptoms. Several factors contribute to the phenotypic variability of WD. The WD-causing mutations produce a wide range of changes in stability, activity, intracellular localization, and trafficking of ATP7B; the nonpathogenic genetic polymorphisms may contribute to the phenotype. In Atp7b(-/-) mice, a mouse model of WD, an abnormal intracellular distribution of copper in the liver triggers distinct changes in the transcriptome; these mRNA profiles might be used to more specifically define disease progression. The major effect of accumulating copper on lipid metabolism and especially cholesterol homeostasis in mice and humans suggests the importance of fat and cholesterol metabolism as modifying factors in WD.

  1. Bioartificial liver: current status.

    Science.gov (United States)

    Pless, G; Sauer, I M

    2005-11-01

    Liver failure remains a life-threatening syndrome. With the growing disparity between the number of suitable donor organs and the number of patients awaiting transplantation, efforts have been made to optimize the allocation of organs, to find alternatives to cadaveric liver transplantation, and to develop extracorporeal methods to support or replace the function of the failing organ. An extracorporeal liver support system has to provide the main functions of the liver: detoxification, synthesis, and regulation. The understanding that the critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared by the failing liver led to the development of artificial filtration and adsorption devices (artificial liver support). Based on this hypothesis, the removal of lipophilic, albumin-bound substances, such as bilirubin, bile acids, metabolites of aromatic amino acids, medium-chain fatty acids, and cytokines, should be beneficial to the clinical course of a patient in liver failure. Artificial detoxification devices currently under clinical evaluation include the Molecular Adsorbent Recirculating System (MARS), Single-Pass Albumin Dialysis (SPAD), and the Prometheus system. The complex tasks of regulation and synthesis remain to be addressed by the use of liver cells (bioartificial liver support). The Extracorporeal Liver Assist Device (ELAD), HepatAssist, Modular Extracorporeal Liver Support system (MELS), and the Amsterdam Medical Center Bioartificial Liver (AMC-BAL) are bioartificial systems. This article gives a brief overview on these artificial and bioartificial devices and discusses remaining obstacles.

  2. Liver disease in pregnancy

    Institute of Scientific and Technical Information of China (English)

    Noel M Lee; Carla W Brady

    2009-01-01

    Liver diseases in pregnancy may be categorized into liver disorders that occur only in the setting of pregnancy and liver diseases that occur coincidentally with pregnancy. Hyperemesis gravidarum, preeclampsia/eclampsia, syndrome of hemolysis, elevated liver tests and low platelets (HELLP), acute fatty liver of pregnancy, and intrahepatic cholestasis of pregnancy are pregnancy-specific disorders that may cause elevations in liver tests and hepatic dysfunction. Chronic liver diseases, including cholestatic liver disease, autoimmune hepatitis, Wilson disease, and viral hepatitis may also be seen in pregnancy. Management of liver disease in pregnancy requires collaboration between obstetricians and gastroenterologists/hepatologists. Treatment of pregnancy-specific liver disorders usually involves delivery of the fetus and supportive care, whereas management of chronic liver disease in pregnancy is directed toward optimizing control of the liver disorder. Cirrhosis in the setting of pregnancy is less commonly observed but offers unique challenges for patients and practitioners. This article reviews the epidemiology, pathophysiology, diagnosis, and management of liver diseases seen in pregnancy.

  3. Murine fertilized ovum, blastomere and morula cells lacking SP phenotype

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In the field of stem cell research, SP (side population) phenotype is used to define the property that cells maintain a high efflux capability for some fluorescent dye, such as Hoechst 33342. Recently, many researches proposed that SP phenotype is a phenotype shared by some stem cells and some progenitor cells, and that SP phenotype is regarded as a candidate purification marker for stem cells. In this research, murine fertilized ova (including conjugate and single nucleus fertilized ova), 2-cell stage and 8-cell stage blastomeres, morulas and blastocysts were isolated and directly stained by Hoechst 33342 dye. The results show that fertilized ovum, blastomere and morula cells do not demonstrate any ability to efflux the dye. However, the inner cell mass (ICM) cells of blastocyst exhibit SP phenotype, which is consistent with the result of embryonic stem cells (ESCs) in vitro. These results indicate that the SP phenotype of ICM-derived ESCs is an intrinsic property and independent of the culture condition in vitro, and that SP phenotype is one of the characteristics of at least some pluripotent stem cells, but is not shared by totipotent stem cells. In addition, the result that the SP phenotype of ICM cells disappeared when the inhibitor verapamil was added into medium implies that the SP phenotype is directly associated with ABCG2. These results suggest that not all the stem cells demonstrate SP phenotype, and that SP phenotype might act as a purification marker for partial stem cells such as some pluripotent embryonic stem cells and multipotent adult stem cells, but not for all stem cells exampled by the totipotent stem cells in the very early stage of mouse embryos.

  4. Space maintainers in dentistry: past to present.

    Science.gov (United States)

    Setia, Vikas; Pandit, Inder Kumar; Srivastava, Nikhil; Gugnani, Neeraj; Sekhon, Harveen Kaur

    2013-10-01

    Early orthodontic interventions are often initiated in the developing dentition to promote favourable developmental changes. Interceptive orthodontic can eliminate or reduce the severity of a developing malocclusion, the complexity of orthodontic treatment, overall treatment time and cost. The safest way to prevent future malocclusions from tooth loss is to place a space maintainer that is effective and durable. An appropriate use of space maintainer is advocated to hold the space until the eruption of permanent teeth. This case report describes the various changing trends in use of space maintainers: conventional band and loop, prefabricated band with custom made loop and glass fibre reinforced composite resins as space maintainers.

  5. Apoptosis and Necrosis in the Liver

    Science.gov (United States)

    Guicciardi, Maria Eugenia; Malhi, Harmeet; Mott, Justin L.; Gores, Gregory J.

    2013-01-01

    Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of “programmed” necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article. PMID:23720337

  6. Autoimmune liver disease panel

    Science.gov (United States)

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cholangitis (formerly called primary biliary cirrhosis). This group of tests ...

  7. Alcoholic liver disease

    Science.gov (United States)

    Liver disease due to alcohol; Cirrhosis or hepatitis - alcoholic; Laennec's cirrhosis ... Alcoholic liver disease occurs after years of heavy drinking. Over time, scarring and cirrhosis can occur. Cirrhosis is the ...

  8. Lysophosphatidylinositol-acyltransferase-1 (LPIAT1 is required to maintain physiological levels of PtdIns and PtdInsP(2 in the mouse.

    Directory of Open Access Journals (Sweden)

    Karen E Anderson

    Full Text Available We disrupted the gene encoding lysophosphatidylinositol-acyltransferase-1 (LPIAT1 in the mouse with the aim of understanding its role in determining cellular phosphoinositide content. LPIAT1(-/- mice were born at lower than Mendelian ratios and exhibited a severe developmental brain defect. We compared the phospholipid content of livers and brains from LPIAT1(-/- and LPIAT1(+/+ littermates by LC-ESI/MS. In accord with previous studies, the most abundant molecular species of each phosphoinositide class (PtdIns, PtdInsP, PtdInsP2 and PtdInsP3 possessed a C38∶4 complement of fatty-acyl esters (C18∶0 and C20∶4 are usually assigned to the sn-1 and sn-2 positions, respectively. LPIAT1(-/- liver and brain contained relatively less of the C38∶4 species of PtdIns, PtdInsP and PtdInsP2 (dropping from 95-97% to 75-85% of the total species measured for each lipid class and relatively more of the less abundant species (PtdInsP3 less abundant species were below our quantification levels. The increases in the less abundant PtdIns and PtdInsP2 species did not compensate for the loss in C38∶4 species, resulting in a 26-44% reduction in total PtdIns and PtdInsP2 levels in both brain and liver. LPIAT1(-/- brain and liver also contained increased levels of C18∶0 lyso-PtdIns (300% and 525% respectively indicating a defect in the reacylation of this molecule. LPIAT1(-/- brain additionally contained significantly reduced C38∶4 PC and PE levels (by 47% and 55% respectively, possibly contributing to the phenotype in this organ. The levels of all other molecular species of PC, PE, PS and PA measured in the brain and liver were very similar between LPIAT1(-/- and LPIAT1(+/+ samples. These results suggest LPIAT1 activity plays a non-redundant role in maintaining physiological levels of PtdIns within an active deacylation/reacylation cycle in mouse tissues. They also suggest that this pathway must act in concert with other, as yet unidentified, mechanisms to

  9. Alcohol and liver, 2010

    Institute of Scientific and Technical Information of China (English)

    Natalia; A; Osna

    2010-01-01

    Liver is known as an organ that is primarily affected by alcohol. Alcoholic liver disease (ALD) is the cause of an increased morbidity and mortality worldwide. Progression of ALD is driven by "second hits". These second hits include the complex of nutritional, pharmacological, genetic and viral factors, which aggravate liver pathology. However, in addition to liver failure, ethanol causes damage to other organs and systems. These extrahepatic manifestations are regulated via the similar hepatitis mechanisms...

  10. Percutaneous liver biopsy.

    Science.gov (United States)

    Rustagi, Tarun; Newton, Eric; Kar, Premashish

    2010-01-01

    Percutaneous liver biopsy has been performed for more than 120 years, and remains an important diagnostic procedure for the management of hepatobiliary disorders. Modern biochemical, immunologic, and radiographic techniques have facilitated the diagnosis and management of liver diseases but have not made liver biopsy obsolete. This comprehensive review article will discuss the history of development of percutaneous liver biopsy, its indications, contraindications, complications and the various aspects of the biopsy procedure in detail.

  11. Autophagy in the liver: cell's cannibalism and beyond.

    Science.gov (United States)

    Flores-Toro, Joseph A; Go, Kristina L; Leeuwenburgh, Christiaan; Kim, Jae-Sung

    2016-08-01

    Chronic liver disease and its progression to liver failure are induced by various etiologies including viral infection, alcoholic and nonalcoholic hepatosteatosis. It is anticipated that the prevalence of fatty liver disease will continue to rise due to the growing incidence of obesity and metabolic disorder. Evidence is accumulating to indicate that the onset of fatty liver disease is causatively linked to mitochondrial dysfunction and abnormal lipid accumulation. Current treatment options for this disease are limited. Autophagy is an integral catabolic pathway that maintains cellular homeostasis both selectively and nonselectively. As mitophagy and lipophagy selectively remove dysfunctional mitochondria and excess lipids, respectively, stimulation of autophagy could have therapeutic potential to ameliorate liver function in steatotic patients. This review highlights our up-to-date knowledge on mechanistic roles of autophagy in the pathogenesis of fatty liver disease and its vulnerability to surgical stress, with an emphasis on mitophagy and lipophagy.

  12. Polycystic liver disease: an overview of pathogenesis, clinical manifestations and management

    NARCIS (Netherlands)

    Cnossen, W.R.; Drenth, J.P.H.

    2014-01-01

    Polycystic liver disease (PLD) is the result of embryonic ductal plate malformation of the intrahepatic biliary tree. The phenotype consists of numerous cysts spread throughout the liver parenchyma. Cystic bile duct malformations originating from the peripheral biliary tree are called Von Meyenburg

  13. Resistance of activated stellate cells to cell death in liver fibrosis : mechanisms and targets for intervention

    NARCIS (Netherlands)

    Dunning, Sandra

    2008-01-01

    In the normal liver, the hepatic stellate cell has a quiescent (i.e. non-proliferating) phenotype. It is the main storage site for vitamin A (retinoids) and it produces the appropriate quality and quantity of extracellular matrix. In chronic liver injury, a sustained wound healing response takes

  14. Zonation of glucose and fatty acid metabolism in the liver : Mechanism and metabolic consequences

    NARCIS (Netherlands)

    Hijmans, Brenda S.; Greffiorst, Aldo; Oosterveer, Maaike H.; Groen, Albert K.

    2014-01-01

    The liver is generally considered as a relatively homogeneous organ containing four different cell types. It is however well-known that the liver is not homogeneous and consists of clearly demarcated metabolic zones. Hepatocytes from different zones show phenotypical heterogeneity in metabolic featu

  15. Zonation of glucose and fatty acid metabolism in the liver : Mechanism and metabolic consequences

    NARCIS (Netherlands)

    Hijmans, Brenda S.; Greffiorst, Aldo; Oosterveer, Maaike H.; Groen, Albert K.

    2014-01-01

    The liver is generally considered as a relatively homogeneous organ containing four different cell types. It is however well-known that the liver is not homogeneous and consists of clearly demarcated metabolic zones. Hepatocytes from different zones show phenotypical heterogeneity in metabolic featu

  16. Diet and Your Liver

    Science.gov (United States)

    ... and to do them for a long time. Eating an unhealthy diet can lead to liver disease. For example, ... and can help repair some liver damage. An unhealthy diet can make the liver ... diet include? • Eating foods from all the food groups: grains, proteins, ...

  17. Liver Tumors (For Parents)

    Science.gov (United States)

    ... Teaching Kids to Be Smart About Social Media Liver Tumors KidsHealth > For Parents > Liver Tumors Print A A A What's in this ... Malignant (Cancerous) Tumors Symptoms Diagnosis Treatment Coping The liver is the body's largest solid organ. Lying next ...

  18. Alcohol and liver

    Institute of Scientific and Technical Information of China (English)

    Natalia Osna

    2009-01-01

    @@ Liver is a primary site of ethanol metabolism, which makes this organ susceptible to alcohol-induced damage.Alcoholic liver disease (ALD) has many manifestations and complicated pathogenesis. In this Topic Highlight, we included the key reviews that characterize new findings about the mechanisms of ALD development and might be of strong interest for clinicians and researchers involved in liver alcohol studies.

  19. Research Areas: Liver Disease

    Science.gov (United States)

    ... and C, or by genetic mutations. Other liver diseases can be triggered by autoimmune reactions or drug toxicity. The rise in obesity in the United States has led to a rise in nonalcoholic fatty liver disease. Many liver diseases place individuals at higher risk ...

  20. LIVER AND BILIARY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    9.1 Liver Function2007108 Blood pressure changes post liver transplantation in 206 recipients. LIU Hai(刘海),et al. 1st People′s Hosp, Shanghai Jiaotong Univ, Shanghai 200080. Chin J Cardiol 2006;34(10):902-904. Objective To study the blood pressure (BP)changes in the liver transplant recipients.

  1. Hepatic (Liver) Function Panel

    Science.gov (United States)

    ... 1- to 2-Year-Old Blood Test: Hepatic (Liver) Function Panel KidsHealth > For Parents > Blood Test: Hepatic (Liver) Function Panel Print A A A What's in ... Is The hepatic function panel, also known as liver function tests, is a group of seven tests ...

  2. LIVER AND BILIARY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    9.1 Liver cirrhosis and fatty liver2003335 The effects of weight reduction in reversing fatty liver changes in overweight and obese patients.ZHU Huijuan(朱惠娟), et al.Dept Endocrinol, PUMC Hosp,CAMS & PUMC, Beijing 100730. Chin J Intern Med 2003:42(2):98-102.Objective:To study the effects of weight loss on non-

  3. Imaging in liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Settimo Caruso; Roberto Miraglia; Luigi Maruzzelli; Salvatore Gruttadauria; Angelo Luca; Bruno Gridelli

    2009-01-01

    The aim of this study was to illustrate the role of noninvasive imaging tools such as ultrasonography, multidetector row computed tomography, and magnetic resonance imaging in the evaluation of pediatric and adult liver recipients and potential liver donors, and in the detection of potential complications arising from liver transplantation.

  4. LIVER AND BILIARY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    11.1 Liver cirrhosis and fatty liver2003230 The relevance of fatty liver and insulin resistance. LIU Jun(刘军), et al. Dept Endocrinol, Zhong-shan Hosp, Fudan Univ, Shanghai 200032, Shanghai Med J 2003; 16(1): 14-17

  5. HOMOTRANSPLANTATION OF THE LIVER1

    Science.gov (United States)

    Starzl, Thomas E.; Marchioro, Thomas L.; Porter, K. A.; Brettschneider, Lawrence

    2010-01-01

    SUMMARY The feasibility of hepatic homotransplantation has been clearly established in principle inasmuch as several animals are still alive almost 3 years after complete hepatectomy and liver replacement. Both orthotopic and auxiliary operations are complicated surgical techniques. Nevertheless, the results in dogs are comparable to those which can be obtained with homotransplantation of the kidney. In man the problem is more difficult. In patients who have a need for such operations, there is invariably a metabolic disorder more complex than that caused by renal failure. In addition, the new organ must function efficiently from the beginning since its complete functional failure leads to death within a few hours. There is no recourse to an artificial liver to maintain life until the reversal of an injury which is caused by either ischemia or rejection. Nevertheless, research of several kinds may soon make possible the successful use of hepatic transplantation procedures for the definitive treatment of human liver disease as exemplified by the reports in this symposium concerning new techniques of organ preservation, histocompatibility analysis, and immunosuppression. PMID:4963511

  6. SECs (Sinusoidal Endothelial Cells), Liver Microenvironment, and Fibrosis

    Science.gov (United States)

    Natarajan, Vaishaali; Harris, Edward N.

    2017-01-01

    Liver fibrosis is a wound-healing response to chronic liver injury such as alcoholic/nonalcoholic fatty liver disease and viral hepatitis with no FDA-approved treatments. Liver fibrosis results in a continual accumulation of extracellular matrix (ECM) proteins and paves the way for replacement of parenchyma with nonfunctional scar tissue. The fibrotic condition results in drastic changes in the local mechanical, chemical, and biological microenvironment of the tissue. Liver parenchyma is supported by an efficient network of vasculature lined by liver sinusoidal endothelial cells (LSECs). These nonparenchymal cells are highly specialized resident endothelial cell type with characteristic morphological and functional features. Alterations in LSECs phenotype including lack of LSEC fenestration, capillarization, and formation of an organized basement membrane have been shown to precede fibrosis and promote hepatic stellate cell activation. Here, we review the interplay of LSECs with the dynamic changes in the fibrotic liver microenvironment such as matrix rigidity, altered ECM protein profile, and cell-cell interactions to provide insight into the pivotal changes in LSEC physiology and the extent to which it mediates the progression of liver fibrosis. Establishing the molecular aspects of LSECs in the light of fibrotic microenvironment is valuable towards development of novel therapeutic and diagnostic targets of liver fibrosis. PMID:28293634

  7. Amebic liver abscess and polycystic liver disease

    Directory of Open Access Journals (Sweden)

    Karan V. S. Rana

    2013-01-01

    Full Text Available Polycystic liver disease is a rare disorder which remains asymptomatic. Infection of cyst is a major complication and is usually pyogenic. We report a rare case of amebic liver abscess in a patient with polycystic liver disease. In our search we found one such case report. Clinical features and radiological findings are usually sufficient, but atypical history and the presence of multiple hepatic abscesses in CT scan delayed diagnosis in our case. Histopathology of the cyst wall and enzyme immunoassay asserted the diagnosis.

  8. Role of SUPERMAN in maintaining Arabidopsis floral whorl boundaries.

    Science.gov (United States)

    Sakai, H; Medrano, L J; Meyerowitz, E M

    1995-11-09

    The Arabidopsis gene SUPERMAN (SUP) is necessary for the proper spatial development of reproductive floral tissues. Recessive mutations cause extra stamens to form interior to the normal third whorl stamens, at the expense of fourth whorl carpel development. The mutant phenotype is associated with the ectopic expression of the B function genes, AP3 and PI, in the altered floral region, closer to the centre of the flower than in the wild type, and ap3 sup and pi sup double mutants exhibit a phenotype similar to ap3 and pi single mutants. These findings led to SUP being interpreted as an upstream negative regulator of the B function organ-identity genes, acting in the fourth whorl, to establish a boundary between stamen and carpel whorls. Here we show, using molecular cloning and analysis, that it is expressed in the third whorl and acts to maintain this boundary in developing flowers. The putative SUPERMAN protein contains one zinc-finger and a region resembling a basic leucine zipper motif, suggesting a function in transcriptional regulation.

  9. liver-enriched gene 1a and 1b encode novel secretory proteins essential for normal liver development in zebrafish.

    Directory of Open Access Journals (Sweden)

    Changqing Chang

    Full Text Available liver-enriched gene 1 (leg1 is a liver-enriched gene in zebrafish and encodes a novel protein. Our preliminary data suggested that Leg1 is probably involved in early liver development. However, no detailed characterization of Leg1 has been reported thus far. We undertook both bioinformatic and experimental approaches to study leg1 gene structure and its role in early liver development. We found that Leg1 identifies a new conserved protein superfamily featured by the presence of domain of unknown function 781 (DUF781. There are two copies of leg1 in zebrafish, namely leg1a and leg1b. Both leg1a and leg1b are expressed in the larvae and adult liver with leg1a being the predominant form. Knockdown of Leg1a or Leg1b by their respective morpholinos specifically targeting their 5'-UTR each resulted in a small liver phenotype, demonstrating that both Leg1a and Leg1b are important for early liver development. Meanwhile, we found that injection of leg1-ATG(MO, a morpholino which can simultaneously block the translation of Leg1a and Leg1b, caused not only a small liver phenotype but hypoplastic exocrine pancreas and intestinal tube as well. Further examination of leg1-ATG(MO morphants with early endoderm markers and early hepatic markers revealed that although depletion of total Leg1 does not alter the hepatic and pancreatic fate of the endoderm cells, it leads to cell cycle arrest that results in growth retardation of liver, exocrine pancreas and intestine. Finally, we proved that Leg1 is a secretory protein. This intrigued us to propose that Leg1 might act as a novel secreted regulator that is essential for liver and other digestive organ development in zebrafish.

  10. Liver abnormalities in pregnancy.

    Science.gov (United States)

    Than, Nwe Ni; Neuberger, James

    2013-08-01

    Abnormalities of liver function (notably rise in alkaline phosphatase and fall in serum albumin) are common in normal pregnancy, whereas rise in serum bilirubin and aminotransferase suggest either exacerbation of underlying pre-existing liver disease, liver disease related to pregnancy or liver disease unrelated to pregnancy. Pregnant women appear to have a worse outcome when infected with Hepatitis E virus. Liver diseases associated with pregnancy include abnormalities associated hyperemesis gravidarum, acute fatty liver disease, pre-eclampsia, cholestasis of pregnancy and HELLP syndrome. Prompt investigation and diagnosis is important in ensuring a successful maternal and foetal outcome. In general, prompt delivery is the treatment of choice for acute fatty liver, pre-eclampsia and HELLP syndrome and ursodeoxycholic acid is used for cholestasis of pregnancy although it is not licenced for this indication. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. AraPheno: a public database for Arabidopsis thaliana phenotypes

    Science.gov (United States)

    Seren, Ümit; Grimm, Dominik; Fitz, Joffrey; Weigel, Detlef; Nordborg, Magnus; Borgwardt, Karsten; Korte, Arthur

    2017-01-01

    Natural genetic variation makes it possible to discover evolutionary changes that have been maintained in a population because they are advantageous. To understand genotype–phenotype relationships and to investigate trait architecture, the existence of both high-resolution genotypic and phenotypic data is necessary. Arabidopsis thaliana is a prime model for these purposes. This herb naturally occurs across much of the Eurasian continent and North America. Thus, it is exposed to a wide range of environmental factors and has been subject to natural selection under distinct conditions. Full genome sequencing data for more than 1000 different natural inbred lines are available, and this has encouraged the distributed generation of many types of phenotypic data. To leverage these data for meta analyses, AraPheno (https://arapheno.1001genomes.org) provide a central repository of population-scale phenotypes for A. thaliana inbred lines. AraPheno includes various features to easily access, download and visualize the phenotypic data. This will facilitate a comparative analysis of the many different types of phenotypic data, which is the base to further enhance our understanding of the genotype–phenotype map. PMID:27924043

  12. A multi-phenotypic cancer model with cell plasticity.

    Science.gov (United States)

    Zhou, Da; Wang, Yue; Wu, Bin

    2014-09-21

    The conventional cancer stem cell (CSC) theory indicates a hierarchy of CSCs and non-stem cancer cells (NSCCs), that is, CSCs can differentiate into NSCCs but not vice versa. However, an alternative paradigm of CSC theory with reversible cell plasticity among cancer cells has received much attention very recently. Here we present a generalized multi-phenotypic cancer model by integrating cell plasticity with the conventional hierarchical structure of cancer cells. We prove that under very weak assumption, the nonlinear dynamics of multi-phenotypic proportions in our model has only one stable steady state and no stable limit cycle. This result theoretically explains the phenotypic equilibrium phenomena reported in various cancer cell lines. Furthermore, according to the transient analysis of our model, it is found that cancer cell plasticity plays an essential role in maintaining the phenotypic diversity in cancer especially during the transient dynamics. Two biological examples with experimental data show that the phenotypic conversions from NCSSs to CSCs greatly contribute to the transient growth of CSCs proportion shortly after the drastic reduction of it. In particular, an interesting overshooting phenomenon of CSCs proportion arises in three-phenotypic example. Our work may pave the way for modeling and analyzing the multi-phenotypic cell population dynamics with cell plasticity.

  13. Apomixis Allows the Transgenerational Fixation of Phenotypes in Hybrid Plants.

    Science.gov (United States)

    Sailer, Christian; Schmid, Bernhard; Grossniklaus, Ueli

    2016-02-01

    The introduction of apomixis-asexual reproduction through seeds-into crop plants is considered the holy grail of agriculture, as it would provide a mechanism to maintain agriculturally important phenotypes [1, 2]. Apomicts produce clonal offspring, such that apomixis could be used to transgenerationally fix any genotype, including that of F1 hybrids, which are used in agriculture due to their superior vigor and yield [3-9]. However, traits (phenotypes) do not only result from a complex combination of genetic and environmental variation but can also be influenced by epigenetic variation, which can be transgenerationally heritable in plants [10-15]. Hence, it is far from clear whether genetic fixation by apomixis suffices to fix the agriculturally relevant phenotypes of F1 hybrids, in particular because hybridization was recently shown to induce epigenetic changes [16, 17]. Here, we show that the phenotypes of Hieracium pilosella hybrids can be fixed across generations by apomixis. Using a natural apomict, we created 11 hybrid genotypes (lines). In these and a parental line, we analyzed 20 phenotypic traits that are related to plant growth and reproduction. Of the 20 traits, 18 (90%) were stably inherited over two apomictic generations, grown at the same time in a randomized design, in 11 of the 12 lines. Although one hybrid line showed phenotypic instability, our results provide a fundamental proof of principle, demonstrating that apomixis can indeed be used in plant breeding and seed production to fix complex, quantitative phenotypes across generations.

  14. Liver injury from herbal and dietary supplements.

    Science.gov (United States)

    Navarro, Victor J; Khan, Ikhlas; Björnsson, Einar; Seeff, Leonard B; Serrano, Jose; Hoofnagle, Jay H

    2017-01-01

    Herbal and dietary supplements (HDS) are used increasingly both in the United States and worldwide, and HDS-induced liver injury in the United States has increased proportionally. Current challenges in the diagnosis and management of HDS-induced liver injury were the focus of a 2-day research symposium sponsored by the American Association for the Study of Liver Disease and the National Institutes of Health. HDS-induced liver injury now accounts for 20% of cases of hepatotoxicity in the United States based on research data. The major implicated agents include anabolic steroids, green tea extract, and multi-ingredient nutritional supplements. Anabolic steroids marketed as bodybuilding supplements typically induce a prolonged cholestatic but ultimately self-limiting liver injury that has a distinctive serum biochemical as well as histological phenotype. Green tea extract and many other products, in contrast, tend to cause an acute hepatitis-like injury. Currently, however, the majority of cases of HDS-associated liver injury are due to multi-ingredient nutritional supplements, and the component responsible for the toxicity is usually unknown or can only be suspected. HDS-induced liver injury presents many clinical and research challenges in diagnosis, identification of the responsible constituents, treatment, and prevention. Also important are improvements in regulatory oversight of nonprescription products to guarantee their constituents and ensure purity and safety. The confident identification of injurious ingredients within HDS will require strategic alignments among clinicians, chemists, and toxicologists. The ultimate goal should be to prohibit or more closely regulate potentially injurious ingredients and thus promote public safety. (Hepatology 2017;65:363-373).

  15. [Portal perfusion with right gastroepiploic vein flow in liver transplant].

    Science.gov (United States)

    Mendoza-Sánchez, Federico; Javier-Haro, Francisco; Mendoza-Medina, Diego Federico; González-Ojeda, Alejandro; Cortés-Lares, José Antonio; Fuentes-Orozco, Clotilde

    Liver transplantation in patients with liver cirrhosis, portal vein thrombosis, and cavernous transformation of the portal vein, is a complex procedure with high possibility of liver graft dysfunction. It is performed in 2-19% of all liver transplants, and has a significantly high mortality rate in the post-operative period. Other procedures to maintain portal perfusion have been described, however there are no reports of liver graft perfusion using right gastroepiploic vein. A 20 year-old female diagnosed with cryptogenic cirrhosis, with a Child-Pugh score of 7 points (class "B"), and MELD score of 14 points, with thrombosis and cavernous transformation of the portal vein, severe portal hypertension, splenomegaly, a history of upper gastrointestinal bleeding due to oesophageal varices, and left renal agenesis. The preoperative evaluation for liver transplantation was completed, and the right gastroepiploic vein of 1-cm diameter was observed draining to the infrahepatic inferior vena cava and right suprarenal vein. An orthotopic liver transplantation was performed from a non-living donor (deceased on January 30, 2005) using the Piggy-Back technique. Portal vein perfusion was maintained using the right gastroepiploic vein, and the outcome was satisfactory. The patient was discharged 13 days after surgery. Liver transplantation was performed satisfactorily, obtaining an acceptable outcome. In this case, the portal perfusion had adequate blood flow through the right gastroepiploic vein. Copyright © 2015 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  16. An ontology for microbial phenotypes.

    Science.gov (United States)

    Chibucos, Marcus C; Zweifel, Adrienne E; Herrera, Jonathan C; Meza, William; Eslamfam, Shabnam; Uetz, Peter; Siegele, Deborah A; Hu, James C; Giglio, Michelle G

    2014-11-30

    Phenotypic data are routinely used to elucidate gene function in organisms amenable to genetic manipulation. However, previous to this work, there was no generalizable system in place for the structured storage and retrieval of phenotypic information for bacteria. The Ontology of Microbial Phenotypes (OMP) has been created to standardize the capture of such phenotypic information from microbes. OMP has been built on the foundations of the Basic Formal Ontology and the Phenotype and Trait Ontology. Terms have logical definitions that can facilitate computational searching of phenotypes and their associated genes. OMP can be accessed via a wiki page as well as downloaded from SourceForge. Initial annotations with OMP are being made for Escherichia coli using a wiki-based annotation capture system. New OMP terms are being concurrently developed as annotation proceeds. We anticipate that diverse groups studying microbial genetics and associated phenotypes will employ OMP for standardizing microbial phenotype annotation, much as the Gene Ontology has standardized gene product annotation. The resulting OMP resource and associated annotations will facilitate prediction of phenotypes for unknown genes and result in new experimental characterization of phenotypes and functions.

  17. Genotype phenotype classification of hepatocellular adenoma

    Institute of Scientific and Technical Information of China (English)

    Paulette Bioulac-Sage; Jean Frédéric Blanc; Sandra Rebouissou; Charles Balabaud; Jessica Zucman-Rossi

    2007-01-01

    Studies that compare tumor genotype with phenotype have provided the basis of a new histological/molecular classification of hepatocellular adenomas. Based on two molecular criteria (presence of a TCF1/HNF1α or β-catenin mutation), and an additional histological criterion (presence or absence of an inflammatory infiltrate), subgroups of hepatocellular adenoma can be defined and distinguished from focal nodular hyperplasia. Analysis of 96 hepatocellular adenomas performed by a French collaborative network showed that they can be divided into four broad subgroups: the first one is defined by the presence of mutations in TCF1 gene inactivating the hepatocyte nuclear factor 1 (HNF1α); the second by the presence of β-catenin activating mutations; the category without mutations of HNF1α or β-catenin is further divided into 2 subgroups depending on the presence or absence of inflammation. Therefore, the approach to the diagnosis of problematic benign hepatocytic nodules may be entering a new era directed by new molecular information. It is hoped that immunohistological tools will improve significantly diagnosis of liver biopsy in our ability to distinguish hepatocellular adenoma from focal nodular hyperplasia (FNH), and to delineate clinically meaningful entities within each group to define the best clinical management. The optimal care of patients with a liver nodule will benefit from the recent knowledge coming from molecular biology and the combined expertise of hepatologists, pathologists, radiologists, and surgeons.

  18. Sources and Information: Maintaining Institutional Integrity.

    Science.gov (United States)

    Palmer, Jim; Zwemer, Diane

    1985-01-01

    Provides an annotated bibliography of ERIC materials dealing with the community college mission, educational quality, maintaining an effective faculty, effects and management of retrenchment, and the state role in community college education. (LAL)

  19. Coastal Maintained Channels in US waters

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This layer shows coastal channels and waterways that are maintained and surveyed by the U.S. Army Corps of Engineers (USACE). These channels are necessary...

  20. Permanent traffic counters maintained by the NMDOT

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — A point dataset representing the permanent traffic counters maintained by the NMDOT. Event mapped dataset by LRS info provided by Traffic group.

  1. Maintaining Contour Trees of Dynamic Terrains

    DEFF Research Database (Denmark)

    Agarwal, Pankaj K.; Mølhave, Thomas; Revsbæk, Morten

    2015-01-01

    We study the problem of maintaining the contour tree T of a terrain Sigma, represented as a triangulated xy-monotone surface, as the heights of its vertices vary continuously with time. We characterize the combinatorial changes in T and how they relate to topological changes in Sigma. We present...... a kinetic data structure (KDS) for maintaining T efficiently. It maintains certificates that fail, i.e., an event occurs, only when the heights of two adjacent vertices become equal or two saddle vertices appear on the same contour. Assuming that the heights of two vertices of Sigma become equal only O(1......) times and these instances can be computed in O(1) time, the KDS processes O(kappa + n) events, where n is the number of vertices in Sigma and kappa is the number of events at which the combinatorial structure of T changes, and processes each event in O(log n) time. The KDS can be extended to maintain...

  2. Space Maintainers in Dentistry: Past to Present

    OpenAIRE

    Setia, Vikas; Pandit, Inder Kumar; Srivastava, Nikhil; Gugnani, Neeraj; Sekhon, Harveen Kaur

    2013-01-01

    Early orthodontic interventions are often initiated in the developing dentition to promote favourable developmental changes. Interceptive orthodontic can eliminate or reduce the severity of a developing malocclusion, the complexity of orthodontic treatment, overall treatment time and cost. The safest way to prevent future malocclusions from tooth loss is to place a space maintainer that is effective and durable. An appropriate use of space maintainer is advocated to hold the space until the e...

  3. Syndromic (phenotypic diarrhea in early infancy

    Directory of Open Access Journals (Sweden)

    Bodemer Christine

    2008-02-01

    Full Text Available Abstract Syndromic diarrhea (SD, also known as phenotypic diarrhea (PD or tricho-hepato-enteric syndrome (THE, is a congenital enteropathy presenting with early-onset of severe diarrhea requiring parenteral nutrition (PN. To date, no epidemiological data are available. The estimated prevalence is approximately 1/300,000–400,000 live births in Western Europe. Ethnic origin does not appear to be associated with SD. Infants are born small for gestational age and present with facial dysmorphism including prominent forehead and cheeks, broad nasal root and hypertelorism. Hairs are woolly, easily removed and poorly pigmented. Severe and persistent diarrhea starts within the first 6 months of life (≤ 1 month in most cases and is accompanied by severe malabsorption leading to early and relentless protein energy malnutrition with failure to thrive. Liver disease affects about half of patients with extensive fibrosis or cirrhosis. There is currently no specific biochemical profile, though a functional T-cell immune deficiency with defective antibody production was reported. Microscopic analysis of the hair show twisted hair (pili torti, aniso- and poilkilotrichosis, and trichorrhexis nodosa. Histopathological analysis of small intestine biopsy shows non-specific villous atrophy with low or no mononuclear cell infiltration of the lamina propria, and no specific histological abnormalities involving the epithelium. The etiology remains unknown. The frequent association of the disorder with parental consanguinity and/or affected siblings suggests a genetic origin with an autosomal recessive mode of transmission. Early management consists of total PN. Some infants have a rather milder phenotype with partial PN dependency or require only enteral feeding. Prognosis of this syndrome is poor, but most patients now survive, and about half of the patients may be weaned from PN at adolescence, but experience failure to thrive and final short stature. Disease name

  4. Obesity and Liver Cancer.

    Science.gov (United States)

    Aleksandrova, Krasimira; Stelmach-Mardas, Marta; Schlesinger, Sabrina

    Obesity and related metabolic disorders have become globally prevalent posing a challenge for the chronically damaged liver and predisposing the development and progression of cancer. The rising phenomenon of "obesity epidemic" may provide means for understanding why liver cancer is one of the few malignancies with rising incidence in developed countries over the last decades. Non-alcoholic fatty liver disease associated with obesity, insulin resistance, and type 2 diabetes is an increasingly recognized trigger for liver cancer in Western populations characterized by low prevalence of established risk factors for liver cancer such as viral hepatitis and hepatotoxin exposure. Accumulating evidence has established an association between higher body mass index as an indicator of general obesity and higher risk of primary liver cancer. The associations are stronger in men, in patients with underlying liver disease and in white ethnic groups. Abdominal obesity, weight gain in adult life and metabolic factors related to visceral fat accumulation were also suggested as important risk factors for liver cancer; however, more studies are needed to evaluate these associations. The association of obesity and metabolic parameters with liver cancer survival remains controversial. It is unclear which exact mechanisms could provide links between obesity and liver cancer risk. Recent evidence has implicated several molecular pathways in obesity-associated liver cancer. These include insulin resistance leading to increased levels of insulin and insulin-like growth factors, chronic inflammation, adipose tissue remodeling, pro-inflammatory cytokine and adipokine secretion, and altered gut microbiota. These mechanisms coincide with inflammatory and metabolic processes occurring in non-alcoholic fatty liver disease predisposing cancer development and progression. In the context of the current evidence, better understanding of the role of obesity and related metabolic factors may help in

  5. High-throughput mouse phenotyping.

    Science.gov (United States)

    Gates, Hilary; Mallon, Ann-Marie; Brown, Steve D M

    2011-04-01

    Comprehensive phenotyping will be required to reveal the pleiotropic functions of a gene and to uncover the wider role of genetic loci within diverse biological systems. The challenge will be to devise phenotyping approaches to characterise the thousands of mutants that are being generated as part of international efforts to acquire a mutant for every gene in the mouse genome. In order to acquire robust datasets of broad based phenotypes from mouse mutants it is necessary to design and implement pipelines that incorporate standardised phenotyping platforms that are validated across diverse mouse genetics centres or mouse clinics. We describe here the rationale and methodology behind one phenotyping pipeline, EMPReSSslim, that was designed as part of the work of the EUMORPHIA and EUMODIC consortia, and which exemplifies some of the challenges facing large-scale phenotyping. EMPReSSslim captures a broad range of data on diverse biological systems, from biochemical to physiological amongst others. Data capture and dissemination is pivotal to the operation of large-scale phenotyping pipelines, including the definition of parameters integral to each phenotyping test and the associated ontological descriptions. EMPReSSslim data is displayed within the EuroPhenome database, where a variety of tools are available to allow the user to search for interesting biological or clinical phenotypes. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Poplar maintains zinc homeostasis with heavy metal genes HMA4 and PCS1

    Science.gov (United States)

    Adams, Joshua P.; Adeli, Ardeshir; Hsu, Chuan-Yu; Harkess, Richard L.; Page, Grier P.; dePamphilis, Claude W.; Schultz, Emily B.; Yuceer, Cetin

    2011-01-01

    Perennial woody species, such as poplar (Populus spp.) must acquire necessary heavy metals like zinc (Zn) while avoiding potential toxicity. Poplar contains genes with sequence homology to genes HMA4 and PCS1 from other species which are involved in heavy metal regulation. While basic genomic conservation exists, poplar does not have a hyperaccumulating phenotype. Poplar has a common indicator phenotype in which heavy metal accumulation is proportional to environmental concentrations but excesses are prevented. Phenotype is partly affected by regulation of HMA4 and PCS1 transcriptional abundance. Wild-type poplar down-regulates several transcripts in its Zn-interacting pathway at high Zn levels. Also, overexpressed PtHMA4 and PtPCS1 genes result in varying Zn phenotypes in poplar; specifically, there is a doubling of Zn accumulation in leaf tissues in an overexpressed PtPCS1 line. The genomic complement and regulation of poplar highlighted in this study supports a role of HMA4 and PCS1 in Zn regulation dictating its phenotype. These genes can be altered in poplar to change its interaction with Zn. However, other poplar genes in the surrounding pathway may maintain the phenotype by inhibiting drastic changes in heavy metal accumulation with a single gene transformation. PMID:21504875

  7. [Liver and sport].

    Science.gov (United States)

    Watelet, J

    2008-11-01

    The liver is a vital organ and plays a central role in energy exchange, protein synthesis as well as the elimination of waste products from the body. Acute and chronic injury may disturb a variety of liver functions to different degrees. Over the last three decades, the effects of physical activity and competitive sport on the liver have been described by various investigators. These include viral hepatitis and drug-induced liver disorders. Herein, we review acute and chronic liver diseases potentially caused by sport. Team physicians, trainers and others, responsible for the health of athletes, should be familiar with the risk factors, clinical features, and consequences of liver diseases that occur in sports.

  8. A mathematical model of cancer cells with phenotypic plasticity

    Directory of Open Access Journals (Sweden)

    Da Zhou

    2015-12-01

    Full Text Available Purpose: The phenotypic plasticity of cancer cells is recently becoming a cutting-edge research area in cancer, which challenges the cellular hierarchy proposed by the conventional cancer stem cell theory. In this study, we establish a mathematical model for describing the phenotypic plasticity of cancer cells, based on which we try to find some salient features that can characterize the dynamic behavior of the phenotypic plasticity especially in comparison to the hierarchical model of cancer cells. Methods: We model cancer as population dynamics composed of different phenotypes of cancer cells. In this model, not only can cancer cells divide (symmetrically and asymmetrically and die, but they can also convert into other cellular phenotypes. According to the Law of Mass Action, the cellular processes can be captured by a system of ordinary differential equations (ODEs. On one hand, we can analyze the long-term stability of the model by applying qualitative method of ODEs. On the other hand, we are also concerned about the short-term behavior of the model by studying its transient dynamics. Meanwhile, we validate our model to the cell-state dynamics in published experimental data.Results: Our results show that the phenotypic plasticity plays important roles in both stabilizing the distribution of different phenotypic mixture and maintaining the cancer stem cells proportion. In particular, the phenotypic plasticity model shows decided advantages over the hierarchical model in predicting the phenotypic equilibrium and cancer stem cells’ overshoot reported in previous biological experiments in cancer cell lines.Conclusion: Since the validity of the phenotypic plasticity paradigm and the conventional cancer stem cell theory is still debated in experimental biology, it is worthy of theoretically searching for good indicators to distinguish the two models through quantitative methods. According to our study, the phenotypic equilibrium and overshoot

  9. Endovascular management in liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Kyu-Bo Sung

    2006-01-01

    @@ Liver transplantation was developed for the treatment of hepatic failure, and the first human liver transplantation was done in 1963. From the 1990 s,liver transplantation was generally accepted as a treatment modality for both end-stage liver disease and selected liver malignancies. Initially, liver transplantation was started with deceased donor whole-size liver transplantation (whole-size LT) as in other organ transplantation, but there is now a shortage of deceased liver donors has occurred. As a solution, deceased donor split liver transplantation (split LT) began in 1989 and living donor liver transplantation (LDLT) in the early 1990 s. Current liver transplantation techniques include whole-size LT, reduced-size liver transplantation (reduced-size LT), split LT and single or dual LDLT. Two donors give a part of their livers to one adult recipient simultaneously in dual LDLT.

  10. Transjugular liver biopsy.

    Science.gov (United States)

    Ble, Michel; Procopet, Bogdan; Miquel, Rosa; Hernandez-Gea, Virginia; García-Pagán, Juan Carlos

    2014-11-01

    Liver biopsy is still the gold standard for evaluation of acute and chronic liver diseases, despite achievements regarding noninvasive diagnosis and staging in liver diseases. Transjugular liver biopsy (TJLB) has proved a good option when ascites and/or significant coagulopathy precludes a percutaneous approach. Because diagnostic hemodynamic procedures can be performed during the same session, it is useful in many clinical settings, regardless of the absence of percuteaneous contraindications. TJLB is a safe technique able to provide good-quality specimens with a low rate of complications. This article presents an overview of TJLB that discusses the technique, applicability, indications, contraindications, complications, and diagnostic accuracy.

  11. Fumarylacetoacetate hydrolase deficient pigs are a novel large animal model of metabolic liver disease

    Directory of Open Access Journals (Sweden)

    Raymond D. Hickey

    2014-07-01

    FAH-deficiency produced a lethal defect in utero that was corrected by administration of 2-(2-nitro-4-trifluoromethylbenzoyl-1,3 cyclohexanedione (NTBC throughout pregnancy. Animals on NTBC were phenotypically normal at birth; however, the animals were euthanized approximately four weeks after withdrawal of NTBC due to clinical decline and physical examination findings of severe liver injury and encephalopathy consistent with acute liver failure. Biochemical and histological analyses, characterized by diffuse and severe hepatocellular damage, confirmed the diagnosis of severe liver injury. FAH−/− pigs provide the first genetically engineered large animal model of a metabolic liver disorder. Future applications of FAH−/− pigs include discovery research as a large animal model of HT1 and spontaneous acute liver failure, and preclinical testing of the efficacy of liver cell therapies, including transplantation of hepatocytes, liver stem cells, and pluripotent stem cell-derived hepatocytes.

  12. Individualized image guided iso-NTCP based liver cancer SBRT

    Energy Technology Data Exchange (ETDEWEB)

    Dawson, Laura A.; Eccles, Cynthia; Craig, Tim [Princess Margaret Hospital, Toronto (Canada). Radiation Medicine Program

    2006-09-15

    A highly individualized stereotactic body radiotherapy (SBRT) strategy was developed to allow a wide spectrum of patients with liver cancer to be treated. This phase I/II study encompasses individualization of immobilization, radiation planning, PTV margin determination, image guidance strategy and prescription dose. Active breathing control breath hold is used to immobilize the liver when feasible. Image guidance strategies include orthogonal MV images and orthogonal kV fluoroscopy using the diaphragm for a surrogate for the liver, and kV cone beam CT using the liver or tumour for guidance. The prescription dose is individualized to maintain the same estimated risk of radiation-induced liver disease (RILD), based on a normal tissue complication probability (NTCP) model, with a maximum permitted dose of 60 Gy in 6 fractions. Since August 2003, 79 patients with hepatocellular carcinoma (33), intrahepatic cholangiocarcinoma (12) and liver metastases (34) were treated. The median tumour volume was 293 cm{sup 3} (2.9-3088 cm{sup 3}). The median prescribed dose was 36.6 Gy (24.0 Gy-57.0 Gy) in 6 fractions. The median effective liver volume irradiated was 45% (9-80%). Sixty percent of patients were treated with breath hold to immobilize their liver. Intra-fraction reproducibility (s) of the liver with repeat breath holds was excellent (1.5?mm); however inter-fraction reproducibility (s) was worse (3.4 mm). Image guidance reduced the residual systematic and random setup errors significantly.

  13. Free Fatty Acids Differentially Downregulate Chemokines in Liver Sinusoidal Endothelial Cells: Insights into Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    McMahan, Rachel H; Porsche, Cara E; Edwards, Michael G; Rosen, Hugo R

    2016-01-01

    Non-alcoholic fatty liver disease is a prevalent problem throughout the western world. Liver sinusoidal endothelial cells (LSEC) have been shown to play important roles in liver injury and repair, but their role in the underlying pathogenetic mechanisms of non-alcoholic fatty liver disease remains undefined. Here, we evaluated the effects of steatosis on LSEC gene expression in a murine model of non-alcoholic fatty liver disease and an immortalized LSEC line. Using microarray we identified distinct gene expression profiles following exposure to free fatty acids. Gene pathway analysis showed a number of differentially expressed genes including those involved in lipid metabolism and signaling and inflammation. Interestingly, in contrast to hepatocytes, fatty acids led to decreased expression of pro-inflammatory chemokines including CCL2 (MCP-1), CXCL10 and CXCL16 in both primary and LSEC cell lines. Chemokine downregulation translated into a significant inhibition of monocyte migration and LSECs isolated from steatotic livers demonstrated a similar shift towards an anti-inflammatory phenotype. Overall, these pathways may represent a compensatory mechanism to reverse the liver damage associated with non-alcoholic fatty liver disease.

  14. Free Fatty Acids Differentially Downregulate Chemokines in Liver Sinusoidal Endothelial Cells: Insights into Non-Alcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Rachel H McMahan

    Full Text Available Non-alcoholic fatty liver disease is a prevalent problem throughout the western world. Liver sinusoidal endothelial cells (LSEC have been shown to play important roles in liver injury and repair, but their role in the underlying pathogenetic mechanisms of non-alcoholic fatty liver disease remains undefined. Here, we evaluated the effects of steatosis on LSEC gene expression in a murine model of non-alcoholic fatty liver disease and an immortalized LSEC line. Using microarray we identified distinct gene expression profiles following exposure to free fatty acids. Gene pathway analysis showed a number of differentially expressed genes including those involved in lipid metabolism and signaling and inflammation. Interestingly, in contrast to hepatocytes, fatty acids led to decreased expression of pro-inflammatory chemokines including CCL2 (MCP-1, CXCL10 and CXCL16 in both primary and LSEC cell lines. Chemokine downregulation translated into a significant inhibition of monocyte migration and LSECs isolated from steatotic livers demonstrated a similar shift towards an anti-inflammatory phenotype. Overall, these pathways may represent a compensatory mechanism to reverse the liver damage associated with non-alcoholic fatty liver disease.

  15. Prohemostatic Interventions in Liver Surgery

    NARCIS (Netherlands)

    Stellingwerff, Menno; Brandsma, Amarins; Lisman, Ton; Porte, Robert J.

    Surgical procedures of the liver, such as partial liver resections and liver transplantation, are major types of abdominal surgery. Liver surgery can be associated with excessive intraoperative blood loss, not only because the liver is a highly vascularized organ, but also because it plays a central

  16. Maintaining Contour Trees of Dynamic Terrains

    DEFF Research Database (Denmark)

    Agarwal, Pankaj K.; Arge, Lars; Mølhave, Thomas

    We consider maintaining the contour tree T of a piecewise-linear triangulation M that is the graph of a time varying height function h:R2→R. We carefully describe the combinatorial change in T that happen as h varies over time and how these changes relate to topological changes in M. We present...... a kinetic data structure that maintains the contour tree of h over time. Our data structure maintains certificates that fail only when h(v)=h(u) for two adjacent vertices v and u in M, or when two saddle vertices lie on the same contour of M. A certificate failure is handled in O(log(n)) time. We also show...

  17. Signals and Cells Involved in Regulating Liver Regeneration

    Directory of Open Access Journals (Sweden)

    Liang-I. Kang

    2012-12-01

    Full Text Available Liver regeneration is a complex phenomenon aimed at maintaining a constant liver mass in the event of injury resulting in loss of hepatic parenchyma. Partial hepatectomy is followed by a series of events involving multiple signaling pathways controlled by mitogenic growth factors (HGF, EGF and their receptors (MET and EGFR. In addition multiple cytokines and other signaling molecules contribute to the orchestration of a signal which drives hepatocytes into DNA synthesis. The other cell types of the liver receive and transmit to hepatocytes complex signals so that, in the end of the regenerative process, complete hepatic tissue is assembled and regeneration is terminated at the proper time and at the right liver size. If hepatocytes fail to participate in this process, the biliary compartment is mobilized to generate populations of progenitor cells which transdifferentiate into hepatocytes and restore liver size.

  18. Hepatic PPARs: their role in liver physiology, fibrosis and treatment.

    Science.gov (United States)

    Zardi, E M; Navarini, L; Sambataro, G; Piccinni, P; Sambataro, F M; Spina, C; Dobrina, A

    2013-01-01

    Complex molecular and cellular mechanisms are involved in the pathway of liver fibrosis. Activation and transformation of hepatic stellate cells (HSCs) are considered the two main reasons for the cause and development of liver fibrosis. The peroxisome proliferator-activated receptors (PPARs) belonging to the family of ligand-activated transcription factors play a key role in liver homeostasis, regulating adipogenesis and inhibiting fibrogenesis in HSCs. Normal transcriptional function of PPARs contributes to maintain HSCs in quiescent phase. A reduced expression of PPARs in HSCs greatly induces a progression of liver fibrosis and an increased production of collagen. Here, we discuss role and function of PPARs and we take into consideration molecular factors able to reduce PPARs activity in HSCs. Finally, although further validations are needed, we illustrate novel strategies available from in vitro and animal studies on how some PPARs-agonists have been proved effective as antifibrotic substances in liver disease.

  19. A SMALL POPULATION OF LIVER ENDOTHELIAL CELLS UNDERGOES ENDOTHELIAL TO MESENCHYMAL TRANSITION IN RESPONSE TO CHRONIC LIVER INJURY.

    Science.gov (United States)

    Ribera, Jordi; Pauta, Montse; Melgar-Lesmes, Pedro; Cordoba, Bernat; Bosch, Anna; Calvo, Maria; Rodrigo-Torres, Daniel; Sancho-Bru, Pau; Mira, Aurea; Jimenez, Wladimiro; Morales-Ruiz, Manuel

    2017-08-10

    Rising evidence points to endothelial-to-mesenchymal transition (EndMT) as a significant source of the mesenchymal cell population in fibrotic diseases. In this context, we hypothesized that liver endothelial cells undergo EndMT during fibrosis progression. Cirrhosis in mice was induced by CCl4 A transgenic mouse expressing a red fluorescent protein reporter under the control of Tie2 promoter (Tie2-tdTomato) was used to trace the acquisition of EndMT. Sinusoidal vascular connectivity was evaluated by intravital microscopy and high resolution 3D confocal microscopy. A modest but significant fraction of liver endothelial cells from both cirrhotic patients and CCl4-treated Tie2-tdTomato mice acquired an EndMT phenotype characterized by the co-expression of CD31 and α-SMA, compared with non-cirrhotic livers. BMP-7 inhibited the acquisition of EndMT induced by TGF-β1 treatment in cultured MLiECs from control mice. EndMT was also reduced significantly in vivo in cirrhotic Tie2-tdTomato mice treated intraperitoneally with BMP-7 compared with untreated mice (1.9±0.2 vs. 3.8±0.3 %, respectively; p<0.05). The decrease of EndMT in cirrhotic livers correlated with a significant decrease in liver fibrosis (p<0.05) and an improvement in the vascular disorganization rate (p<0.05). We demonstrated the acquisition of the EndMT phenotype by a subpopulation of endothelial cells from cirrhotic livers in both animal models and patients. BMP-7 treatment decreases the occurrence of the EndMT phenotype and has a positive impact on the severity of disease by reducing fibrosis and sinusoidal vascular disorganization. Copyright © 2017, American Journal of Physiology-Gastrointestinal and Liver Physiology.

  20. The Broad Autism Phenotype Questionnaire

    Science.gov (United States)

    Hurley, Robert S. E.; Losh, Molly; Parlier, Morgan; Reznick, J. Steven; Piven, Joseph

    2007-01-01

    The broad autism phenotype (BAP) is a set of personality and language characteristics that reflect the phenotypic expression of the genetic liability to autism, in non-autistic relatives of autistic individuals. These characteristics are milder but qualitatively similar to the defining features of autism. A new instrument designed to measure the…

  1. Plant Phenotype Characterization System

    Energy Technology Data Exchange (ETDEWEB)

    Daniel W McDonald; Ronald B Michaels

    2005-09-09

    This report is the final scientific report for the DOE Inventions and Innovations Project: Plant Phenotype Characterization System, DE-FG36-04GO14334. The period of performance was September 30, 2004 through July 15, 2005. The project objective is to demonstrate the viability of a new scientific instrument concept for the study of plant root systems. The root systems of plants are thought to be important in plant yield and thus important to DOE goals in renewable energy sources. The scientific study and understanding of plant root systems is hampered by the difficulty in observing root activity and the inadequacy of existing root study instrumentation options. We have demonstrated a high throughput, non-invasive, high resolution technique for visualizing plant root systems in-situ. Our approach is based upon low-energy x-ray radiography and the use of containers and substrates (artificial soil) which are virtually transparent to x-rays. The system allows us to germinate and grow plant specimens in our containers and substrates and to generate x-ray images of the developing root system over time. The same plant can be imaged at different times in its development. The system can be used for root studies in plant physiology, plant morphology, plant breeding, plant functional genomics and plant genotype screening.

  2. Maintaining collections with a flat budget

    Directory of Open Access Journals (Sweden)

    Sara E Morris

    2017-03-01

    Full Text Available This paper focuses on the various processes, methods and tough decisions made by the University of Kansas Libraries to provide library materials while maintaining a flat collections budget for over eight years. During this period, those responsible for the Libraries’ collections have implemented quick stop- gap measures, picked all the ‘low-hanging fruit’, and eventually canceled a large journal package. This case study will help other librarians facing the reality of maintaining collections at a time when budgets, changing formats and publication practices are all obstacles to providing patrons with what they need.

  3. Automated Methods to Maintain Aircraft Separation

    Science.gov (United States)

    Lauderdale, Todd

    2011-01-01

    The air traffic control system in the United States has a great track-record for safety. As more aircraft enter the system at a given time, the situation becomes more complex though. Researchers at NASA are attempting to leverage advances in many fields including optimization, data mining, and numerical modeling of systems to improve the air-transportation system maintaining safety while increasing throughput and reducing delays. This talk will give a brief overview of the research at NASA towards modernizing the air-transportation system. It will then focus on the specific area of automation tools for maintaining physical separation between aircraft known as Separation Assurance.

  4. Global phenotypic characterization of bacteria.

    Science.gov (United States)

    Bochner, Barry R

    2009-01-01

    The measure of the quality of a systems biology model is how well it can reproduce and predict the behaviors of a biological system such as a microbial cell. In recent years, these models have been built up in layers, and each layer has been growing in sophistication and accuracy in parallel with a global data set to challenge and validate the models in predicting the content or activities of genes (genomics), proteins (proteomics), metabolites (metabolomics), and ultimately cell phenotypes (phenomics). This review focuses on the latter, the phenotypes of microbial cells. The development of Phenotype MicroArrays, which attempt to give a global view of cellular phenotypes, is described. In addition to their use in fleshing out and validating systems biology models, there are many other uses of this global phenotyping technology in basic and applied microbiology research, which are also described.

  5. Global phenotypic characterization of bacteria

    Science.gov (United States)

    Bochner, Barry R

    2009-01-01

    The measure of the quality of a systems biology model is how well it can reproduce and predict the behaviors of a biological system such as a microbial cell. In recent years, these models have been built up in layers, and each layer has been growing in sophistication and accuracy in parallel with a global data set to challenge and validate the models in predicting the content or activities of genes (genomics), proteins (proteomics), metabolites (metabolomics), and ultimately cell phenotypes (phenomics). This review focuses on the latter, the phenotypes of microbial cells. The development of Phenotype MicroArrays, which attempt to give a global view of cellular phenotypes, is described. In addition to their use in fleshing out and validating systems biology models, there are many other uses of this global phenotyping technology in basic and applied microbiology research, which are also described. PMID:19054113

  6. Liver transplantation in polycystic liver disease

    DEFF Research Database (Denmark)

    Krohn, Paul S; Hillingsø, Jens; Kirkegaard, Preben

    2008-01-01

    OBJECTIVE: Polycystic liver disease (PLD) is a rare, hereditary, benign disorder. Hepatic failure is uncommon and symptoms are caused by mass effects leading to abdominal distension and pain. Liver transplantation (LTX) offers fully curative treatment, but there is still some controversy about...... whether it is a relevant modality considering the absence of liver failure, relative organ shortage, perioperative risks and lifelong immunosuppression. The purpose of this study was to review our experience of LTX for PLD and to compare the survival with the overall survival of patients who underwent LTX....../kidney transplantation. One patient had undergone kidney transplantation 10 years earlier. RESULTS: Median follow-up was 55 months. One patient who underwent combined transplantation died after 5.4 months because of multiorgan failure after re-LTX, and one patient, with well-functioning grafts, died of lymphoma after 7...

  7. EMP-1 is a junctional protein in a liver stem cell line and in the liver.

    Science.gov (United States)

    Lee, Hsuan-Shu; Sherley, James L; Chen, Jeremy J W; Chiu, Chien-Chang; Chiou, Ling-Ling; Liang, Ja-Der; Yang, Pan-Chyr; Huang, Guan-Tarn; Sheu, Jin-Chuan

    2005-09-09

    In an attempt to discover cell markers for liver stem cells, a cDNA microarray analysis was carried out to compare the gene expression profiles between an adult liver stem cell line, Lig-8, and mature hepatocytes. Several genes in the categories of extracellular matrix, cell membrane, cell adhesion, transcription factor, signal molecule, transporter, and metabolic enzyme were shown to be differentially expressed in Lig-8 cells. Among them, epithelial membrane protein (EMP)-1 has been previously implicated with stem cell phenotypes. Antiserum to EMP-1 was produced to localize its expression. On monolayers of Lig-8 cells, EMP-1 was expressed along the intercellular border. In the liver harboring proliferating oval cells, the liver progenitors, EMP-1 was localized as ribbon bands, a staining pattern for epithelial junctions, all the way through bile duct epithelia, oval cell ductules, and into peri-hepatocytic regions. These peri-hepatocytic regions were proved to be bile canaliculi by co-localization of EMP-1 and dipeptidyl peptidase IV, an enzyme located on bile canaliculi. This report is the first to indicate EMP-1 to be a junctional protein in the liver.

  8. Maintaining an Operational Flight Program (OFP)

    Science.gov (United States)

    1991-10-01

    Monitor And Control ( PMAC ), as an example, allows a maintainer to interact with his running OFP. Other specialized environment testing might indicate...paths on the F-15’s Central Computer. Processor Peculiar Tests Specialized testing for unique features of ECSs. Programmable Monitor And Control ( PMAC

  9. How to Maintain a Social Reinforcement Program.

    Science.gov (United States)

    Arkin, Ronald; And Others

    This manual presents methodology for maintaining a social reinforcement system after supervisors in industrial environments have been trained in behavior modification theory and application. The maintenance manual discusses monitoring, evaluation, and integration of a company's employee performance system with the social reinforcement system…

  10. The randomized complexity of maintaining the minimum

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Chaudhuri, Shiva; Radhakrishnan, Jaikumar

    1996-01-01

    The complexity of maintaining a set under the operations Insert, Delete and FindMin is considered. In the comparison model it is shown that any randomized algorithm with expected amortized cost t comparisons per Insert and Delete has expected cost at least n/(e22t)-1 comparisons for FindMin. If F...

  11. Maintaining Contour Trees of Dynamic Terrains

    DEFF Research Database (Denmark)

    Agarwal, Pankaj K.; Arge, Lars; Mølhave, Thomas

    We consider maintaining the contour tree T of a piecewise-linear triangulation M that is the graph of a time varying height function h:R2→R. We carefully describe the combinatorial change in T that happen as h varies over time and how these changes relate to topological changes in M. We present...

  12. Maintaining Hope in the Face of Evil.

    Science.gov (United States)

    Miller, Geri

    2002-01-01

    P. G. Zimbardo (2001) and M. E. P. Seligman (in an interview with S. Carpenter, 2001) discuss evil and hope in response to the September 11, 2001, disaster. The implications for counseling are presented with an emphasis on how counselors can maintain hope for themselves and their clients in the face of evil. (Author)

  13. Maintaining ideal body weight counseling sessions

    Energy Technology Data Exchange (ETDEWEB)

    Brammer, S.H.

    1980-10-09

    The purpose of this program is to provide employees with the motivation, knowledge and skills necessary to maintain ideal body weight throughout life. The target audience for this program, which is conducted in an industrial setting, is the employee 40 years of age or younger who is at or near his/her ideal body weight.

  14. Treating Problem Behaviors Maintained by Negative Reinforcement.

    Science.gov (United States)

    Cipani, Ennio; Spooner, Fred

    1997-01-01

    Identifies four treatment techniques that may be applied when problem behavior is maintained by negative reinforcement: (1) functional communication training; (2) behavioral momentum; (3) differential reinforcement or an alternative escape behavior; and (4) errorless learning. Each of the techniques is defined, and applications and guidelines for…

  15. Maintaining Contour Trees of Dynamic Terrains

    DEFF Research Database (Denmark)

    Agarwal, Pankaj K.; Mølhave, Thomas; Revsbæk, Morten;

    2015-01-01

    We study the problem of maintaining the contour tree T of a terrain Sigma, represented as a triangulated xy-monotone surface, as the heights of its vertices vary continuously with time. We characterize the combinatorial changes in T and how they relate to topological changes in Sigma. We present ...

  16. How Do Positive Views Maintain Life Satisfaction?

    Science.gov (United States)

    Wu, Chia-Huei; Tsai, Ying-Mei; Chen, Lung Hung

    2009-01-01

    This study proposes three mediation pathways to explain how the positive views (perceived control, optimism and self-enhancement) proposed by Cummins and Nistico (Journal of Happiness Studies 3:37-69 2002) maintain life satisfaction. The three pathways were enhancing self-esteem, reducing have-want discrepancy and changing importance perceptions.…

  17. Maintaining strategic momentum : The CEO's agenda

    NARCIS (Netherlands)

    F.M. Maljers (Floris); C.W.F. Baden-Fuller (Charles); F.A.J. van den Bosch (Frans)

    1996-01-01

    textabstractThe question of how the CEO of a large complex organization maintain strategic momentum is addressed. This represents a great challenge when there are no obvious external threats, and no obvious reasons for having a concerted action. The inherent tensions which exist between stability an

  18. Prolactin and liver disease

    NARCIS (Netherlands)

    A.G.C. Bauer (Alexander)

    1982-01-01

    textabstractCirrhosis of the liver is associated with profound endocrinological disturbances. Until recently it was thought that these disturbances were caused mainly by ineffective elimination of hormones by the diseased liver. It is now known that the pathogenesis of disturbed hormonal function in

  19. Bioartificial Liver Support

    Directory of Open Access Journals (Sweden)

    Vincent G Bain

    2001-01-01

    Full Text Available Bioartificial liver support has been increasingly the focus of both basic and clinical research in an attempt to replicate the multiplicity of normal liver function. The concept is attractive because, if it is effective, patients with acute liver failure may be supported until native liver regeneration occurs or, by optimizing their condition, until liver transplantation is possible. Current bioartificial liver support systems utilize primary porcine hepatocytes or transformed human hepatocytes, which are housed within a bioreactor, through which the patient's blood or plasma is pumped in an extracorporeal circuit. The optimal source for the hepatocytes is an area of debate; however, a genetically engineered cell line may provide optimal function. Novel three-dimensional matrices that anchor the hepatocytes are being designed to mimic architectural features of the normal liver. Large multicentre, randomized, controlled trials are ongoing following several pilot studies. Serious side effects such as hemodynamic instability and immune reactions have been infrequent. Much controversy, however, surrounds the issue of possible transmission of pig endogenous retrovirus to humans, and current trials are being carefully monitored. Bioartificial liver support is a promising technology, and the results of current and planned studies are awaited with great interest.

  20. Fatigue after Liver Transplantation

    NARCIS (Netherlands)

    B.T.J. van Ginneken (Berbke)

    2009-01-01

    textabstractLiver transplantation (LTx) has developed from an experimental procedure in the 1960’s to the preferred treatment for end-stage liver disease nowadays. The first human LTx was performed by Starlz and his team in 1963 in Colorado.[1] Unfortunately, this patient died within a few days. The

  1. Liver and Biliary System

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    2011220 Value of liver biopsy in diagnosis of chronic hepatitis B. YANG Fang(杨方) ,et al. 2nd Ward, Shenyang 6th People’s Hosp,Shenyang 110006. Chin J Infect Dis 2011; 29(2):99-103. Objective To explore the value of liver biopsy in diagnosis of the severity of chronic hepatitis

  2. Multiple pyogenic liver abscess

    Institute of Scientific and Technical Information of China (English)

    Mabrouk Bahloul; Anis Chaari; Nadia Bouaziz-Khlaf; Hatem Kallel; Leila Herguefi; Hedi Chelly; Chokri Ben Hamida; Mounir Bouaziz

    2006-01-01

    Multiple pyogenic liver abscesses have been rarely described. We report a fatal case of multiple pyogenic liver abscesses affecting a 38-year-old woman requiring surgical drainage. Evolution was marked by occurrence of a septic shock with multi-organ system failure. The patient died 48 h after surgery. Causes, therapeutics and outcome of the disease are discussed.

  3. Liver and Biliary System

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    9.1.Liver cirrhosis and fatty liver2005376 The role of ribosomal S6 kinase in thepathogenesis of rat hepatic fibrosis.YANG Miaofang(杨妙芳),et al.Dept Gastroenterol,Changzheng Hosp,2nd Milit Med Univ,Shanghai 200003.Chin J Dig 2005;25(2):98-100.

  4. LIVER AND BILIARGY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    8.1 Liver cirrhosis and fatty liver2004100 The clinical feature and prognosis of Aero-monas septicaemia in hepatic cirrhosis: a report of 50 cases. QU Fen (曲芬), et al. Clin Centre, 302nd Hosp PLA, Beijing 100039. Chin J Intern Med 2003; 42 (12): 840 - 846Objective: Aeromonas septicaemia complicating cirrhosis

  5. Alcohol-Related Liver Disease

    Science.gov (United States)

    ... A Life After Diagnosis Support for Chronic Illness Corporate Partnerships Interview with Kristen Hanks Liver Lowdown July ... stomach • enlarged spleen • brain disorders and coma • kidney failure • liver cancer In addition alcoholic liver disease may ...

  6. Mechanism of hard nanomaterial clearance by the liver

    Science.gov (United States)

    Tsoi, Kim M.; MacParland, Sonya A.; Ma, Xue-Zhong; Spetzler, Vinzent N.; Echeverri, Juan; Ouyang, Ben; Fadel, Saleh M.; Sykes, Edward A.; Goldaracena, Nicolas; Kaths, Johann M.; Conneely, John B.; Alman, Benjamin A.; Selzner, Markus; Ostrowski, Mario A.; Adeyi, Oyedele A.; Zilman, Anton; McGilvray, Ian D.; Chan, Warren C.W.

    2016-01-01

    The liver and spleen are major biological barriers to translating nanomedicines because they sequester the majority of administered nanomaterials and prevent delivery to diseased tissue. Here we examined the blood clearance mechanism of administered hard nanomaterials in relation to blood flow dynamics, organ microarchitecture, and cellular phenotype. We found that nanomaterial velocity reduces 1000-fold as they enter and traverse the liver, leading to 7.5 times more nanomaterial interaction with hepatic cells relative to peripheral cells. In the liver, Kupffer cells (84.8%±6.4%), hepatic B cells (81.5±9.3%), and liver sinusoidal endothelial cells (64.6±13.7%) interacted with administered PEGylated quantum dots but splenic macrophages took up less (25.4±10.1%) due to differences in phenotype. The uptake patterns were similar for two other nanomaterial types and five different surface chemistries. Potential new strategies to overcome off-target nanomaterial accumulation may involve manipulating intra-organ flow dynamics and modulating cellular phenotype to alter hepatic cell interaction. PMID:27525571

  7. Mechanism of hard-nanomaterial clearance by the liver

    Science.gov (United States)

    Tsoi, Kim M.; Macparland, Sonya A.; Ma, Xue-Zhong; Spetzler, Vinzent N.; Echeverri, Juan; Ouyang, Ben; Fadel, Saleh M.; Sykes, Edward A.; Goldaracena, Nicolas; Kaths, Johann M.; Conneely, John B.; Alman, Benjamin A.; Selzner, Markus; Ostrowski, Mario A.; Adeyi, Oyedele A.; Zilman, Anton; McGilvray, Ian D.; Chan, Warren C. W.

    2016-11-01

    The liver and spleen are major biological barriers to translating nanomedicines because they sequester the majority of administered nanomaterials and prevent delivery to diseased tissue. Here we examined the blood clearance mechanism of administered hard nanomaterials in relation to blood flow dynamics, organ microarchitecture and cellular phenotype. We found that nanomaterial velocity reduces 1,000-fold as they enter and traverse the liver, leading to 7.5 times more nanomaterial interaction with hepatic cells relative to peripheral cells. In the liver, Kupffer cells (84.8 +/- 6.4%), hepatic B cells (81.5 +/- 9.3%) and liver sinusoidal endothelial cells (64.6 +/- 13.7%) interacted with administered PEGylated quantum dots, but splenic macrophages took up less material (25.4 +/- 10.1%) due to differences in phenotype. The uptake patterns were similar for two other nanomaterial types and five different surface chemistries. Potential new strategies to overcome off-target nanomaterial accumulation may involve manipulating intra-organ flow dynamics and modulating the cellular phenotype to alter hepatic cell interactions.

  8. Mitochondrial genome regulates mitotic fidelity by maintaining centrosomal homeostasis.

    Science.gov (United States)

    Donthamsetty, Shashikiran; Brahmbhatt, Meera; Pannu, Vaishali; Rida, Padmashree C G; Ramarathinam, Sujatha; Ogden, Angela; Cheng, Alice; Singh, Keshav K; Aneja, Ritu

    2014-01-01

    Centrosomes direct spindle morphogenesis to assemble a bipolar mitotic apparatus to enable error-free chromosome segregation and preclude chromosomal instability (CIN). Amplified centrosomes, a hallmark of cancer cells, set the stage for CIN, which underlies malignant transformation and evolution of aggressive phenotypes. Several studies report CIN and a tumorigenic and/or aggressive transformation in mitochondrial DNA (mtDNA)-depleted cells. Although several nuclear-encoded proteins are implicated in centrosome duplication and spindle organization, the involvement of mtDNA encoded proteins in centrosome amplification (CA) remains elusive. Here we show that disruption of mitochondrial function by depletion of mtDNA induces robust CA and mitotic aberrations in osteosarcoma cells. We found that overexpression of Aurora A, Polo-like kinase 4 (PLK4), and Cyclin E was associated with emergence of amplified centrosomes. Supernumerary centrosomes in rho0 (mtDNA-depleted) cells resulted in multipolar mitoses bearing "real" centrosomes with paired centrioles at the multiple poles. This abnormal phenotype was recapitulated by inhibition of respiratory complex I in parental cells, suggesting a role for electron transport chain (ETC) in maintaining numeral centrosomal homeostasis. Furthermore, rho0 cells displayed a decreased proliferative capacity owing to a G 2/M arrest. Downregulation of nuclear-encoded p53 in rho0 cells underscores the importance of mitochondrial and nuclear genome crosstalk and may perhaps underlie the observed mitotic aberrations. By contrast, repletion of wild-type mtDNA in rho0 cells (cybrid) demonstrated a much lesser extent of CA and spindle multipolarity, suggesting partial restoration of centrosomal homeostasis. Our study provides compelling evidence to implicate the role of mitochondria in regulation of centrosome duplication, spindle architecture, and spindle pole integrity.

  9. [Xenotransplantation of the liver].

    Science.gov (United States)

    Winkler, M; Schlitt, H J

    1999-01-01

    The development of pigs transgenic for human regulators of complement activation resulted in the nearly total elimination of episodes of hyperacute rejection following discordant solid organ xenotransplantation. Following discordant heart or kidney transplantation, in subhuman primates, graft survival rates of up to several months can be observed. In contrast to these organs, the xenotransplantation of the liver is associated with the inherent problem of the immunological and metabolic compatibility of the large variety of xenoproteins generated. Based on a review of data mainly derived from experimental ex-vivo xenoliver perfusions in patients with hepatic coma, whole organ orthotopic or heterotopic liver xenotransplantation currently is not likely to become a relevant option for the treatment of patients with endstage liver failure. In contrast, clinical studies utilizing different forms of bioartificial liver assist devices are currently underway. Based on preliminary data published, this form of liver support therapy might enter the clinic in the near future.

  10. Liver cancer oncogenomics

    DEFF Research Database (Denmark)

    Marquardt, Jens U; Andersen, Jesper B

    2015-01-01

    Primary liver cancers are among the most rapidly evolving malignant tumors worldwide. An underlying chronic inflammatory liver disease, which precedes liver cancer development for several decades and frequently creates a pro-oncogenic microenvironment, impairs progress in therapeutic approaches....... Molecular heterogeneity of liver cancer is potentiated by a crosstalk between epithelial tumor and stromal cells that complicate translational efforts to unravel molecular mechanisms of hepatocarcinogenesis with a drugable intend. Next-generation sequencing has greatly advanced our understanding of cancer...... development. With regards to liver cancer, the unprecedented coverage of next-generation sequencing has created a detailed map of genetic alterations and identified key somatic changes such as CTNNB1 and TP53 as well as several previously unrecognized recurrent disease-causing alterations that could...

  11. A new veno-venous bypass type for ex-vivo liver resection in dogs

    Institute of Scientific and Technical Information of China (English)

    Peng Lei; Shi-Qi Liu; Xiao-Hai Cui; Yi Lv; Ge Zhao; Jian-Hui Li

    2013-01-01

      Ex-vivo liver resection is a procedure in which the liver is completely removed, perfused and after bench surgery, the liver is autotransplanted to the original site. Ex-vivo liver resection is an important treatment for unresectable liver tumors. This surgical procedure requires long operation time, during which blood flow must be carefully maintained to avoid venous congestion. An effective veno-venous bypass (VVB) may meet this requirement. The present study was to test our new designed VVB device which comprised one heparinized polyvinylchloride tube and three magnetic rings. The efficacy of this device was tested in five dogs. A VVB was established in 6-10 minutes. There was no leakage during the procedure. Hemodynamics was stable at anhepatic phase, which indicated that the bypass was successful. This newly-developed VVB device maintained circulation stability during ex-vivo liver resection in our dog model and thus, this VVB device significantly shortened the operation time.

  12. Phenotypic variation in Azospirillum brasilense exposed to starvation.

    Science.gov (United States)

    Lerner, Anat; Valverde, Angel; Castro-Sowinski, Susana; Lerner, Hadas; Okon, Yaacov; Burdman, Saul

    2010-08-01

    Bacteria have developed mechanisms that allow them maintaining cell viability during starvation and resuming growth when nutrients become available. Among these mechanisms are adaptive mutations and phase variation, which are often associated with DNA rearrangements. Azospirillum brasilense is a Gram-negative, nitrogen-fixing, plant growth-promoting rhizobacterium. Here we report phenotypic variants of A. brasilense that were collected after exposure to prolonged starvation or after re-isolation from maize roots. The variants differed in several features from the parental strains, including pigmentation, aggregation ability, EPS amount and composition and LPS structure. One of the phenotypic variants, overproducing EPS and showing an altered LPS structure, was further characterized and showed differential response to several stresses and antibiotics relative to its parental strain. Characterization of the variants by repetitive-PCR revealed that phenotypic variation was often associated with DNA rearrangements.

  13. Phenotypic plasticity, costs of phenotypes, and costs of plasticity

    DEFF Research Database (Denmark)

    Callahan, Hilary S; Maughan, Heather; Steiner, Uli

    2008-01-01

    Why are some traits constitutive and others inducible? The term costs often appears in work addressing this issue but may be ambiguously defined. This review distinguishes two conceptually distinct types of costs: phenotypic costs and plasticity costs. Phenotypic costs are assessed from patterns...... of covariation, typically between a focal trait and a separate trait relevant to fitness. Plasticity costs, separable from phenotypic costs, are gauged by comparing the fitness of genotypes with equivalent phenotypes within two environments but differing in plasticity and fitness. Subtleties associated with both...... types of costs are illustrated by a body of work addressing predator-induced plasticity. Such subtleties, and potential interplay between the two types of costs, have also been addressed, often in studies involving genetic model organisms. In some instances, investigators have pinpointed the mechanistic...

  14. Liver biopsy in liver patients with coagulopathy

    DEFF Research Database (Denmark)

    Ott, P.; Gronbaek, H.; Clausen, M.R.

    2008-01-01

    The risk of severe bleeding after liver biopsy is estimated to be 1:12,000 in patients with near normal coagulation (INR 60 billion /l). Beyond these limits, the risk is higher, but still uncertain. The Danish guidelines require INR > 1.5, platelet count

  15. Sex impact on the quality of fatty liver and its genetic determinism in mule ducks.

    Science.gov (United States)

    Marie-Etancelin, C; Retailleau, B; Alinier, A; Vitezica, Z G

    2015-09-01

    Recent changes to French regulations now allow farmers to produce "foie gras" from both male and female mule ducks. The aim of this study was to assess the quality of female fatty liver and to compare, from a phenotypic and genetic point of view, liver quality in males and females. A total of 914 mule ducks (591 males and 323 females), hatched in a single pedigree batch, were reared until 86 d of age and then force-fed for 12 d, before being slaughtered. Carcasses and livers were weighed and liver quality was assessed by grading the extent of liver veining and measuring the liver melting rate, either after sterilization of 60 g of liver or pasteurization of 180 g of liver. Sexual dimorphism was observed in favor of males, with a difference of approximately 10% in carcass and liver weights and up to 54% for the liver melting rate. Moreover, one-third of female livers showed moderate to high veining, whereas this was not the case for male livers. The fatty livers of female mule ducks are, therefore, of poorer quality and could not be transformed into a product with the appellation "100% fatty liver." According to sex and parental line, heritability values ranged from 0.12 ± 0.05 to 0.18 ± 0.07 for fatty liver weight and from 0.09 ± 0.05 to 0.18 ± 0.05 for the 2 melting rate traits. The genetic correlations between the fatty liver weight and both melting rates were high (greater than +0.80) in the Muscovy population, whereas in the Pekin population, the liver weight and melting rates were less strongly correlated (estimates ranging from +0.36 ± 0.30 to +0.45 ± 0.28). Selection for lower liver melting rates without reducing the liver weight would, therefore, be easier to achieve in the Pekin population. Finally, as the 2 melting rate measurements are highly correlated (0.91 and over 0.95 for phenotypic and genetic correlations, respectively), we suggest using the easiest method, that is, sterilization of 60 g of liver.

  16. Defining microglial phenotypic diversity and the impact of ageing

    OpenAIRE

    2015-01-01

    Microglia are the resident macrophages of the central nervous system (CNS) and, as key immune effector cells, form the first line of defence. Microglial cells also provide support for maintaining neuronal homeostasis and more generally normal brain physiology and cognitive function. It has been speculated that in order to support homeostasis, microglia adapt to a variety of brain microenvironments leading to regional phenotypic heterogeneity. To date this hypothesis lacks convi...

  17. Function of GATA Factors in the Adult Mouse Liver

    Science.gov (United States)

    Zheng, Rena; Rebolledo-Jaramillo, Boris; Zong, Yiwei; Wang, Liqing; Russo, Pierre; Hancock, Wayne; Stanger, Ben Z.; Hardison, Ross C.; Blobel, Gerd A.

    2013-01-01

    GATA transcription factors and their Friend of Gata (FOG) cofactors control the development of diverse tissues. GATA4 and GATA6 are essential for the expansion of the embryonic liver bud, but their expression patterns and functions in the adult liver are unclear. We characterized the expression of GATA and FOG factors in whole mouse liver and purified hepatocytes. GATA4, GATA6, and FOG1 are the most prominently expressed family members in whole liver and hepatocytes. GATA4 chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) identified 4409 occupied sites, associated with genes enriched in ontologies related to liver function, including lipid and glucose metabolism. However, hepatocyte-specific excision of Gata4 had little impact on gross liver architecture and function, even under conditions of regenerative stress, and, despite the large number of GATA4 occupied genes, resulted in relatively few changes in gene expression. To address possible redundancy between GATA4 and GATA6, both factors were conditionally excised. Surprisingly, combined Gata4,6 loss did not exacerbate the phenotype resulting from Gata4 loss alone. This points to the presence of an unusually robust transcriptional network in adult hepatocytes that ensures the maintenance of liver function. PMID:24367609

  18. Cannabinoid receptor signaling regulates liver development and metabolism.

    Science.gov (United States)

    Liu, Leah Y; Alexa, Kristen; Cortes, Mauricio; Schatzman-Bone, Stephanie; Kim, Andrew J; Mukhopadhyay, Bani; Cinar, Resat; Kunos, George; North, Trista E; Goessling, Wolfram

    2016-02-15

    Endocannabinoid (EC) signaling mediates psychotropic effects and regulates appetite. By contrast, potential roles in organ development and embryonic energy consumption remain unknown. Here, we demonstrate that genetic or chemical inhibition of cannabinoid receptor (Cnr) activity disrupts liver development and metabolic function in zebrafish (Danio rerio), impacting hepatic differentiation, but not endodermal specification: loss of cannabinoid receptor 1 (cnr1) and cnr2 activity leads to smaller livers with fewer hepatocytes, reduced liver-specific gene expression and proliferation. Functional assays reveal abnormal biliary anatomy and lipid handling. Adult cnr2 mutants are susceptible to hepatic steatosis. Metabolomic analysis reveals reduced methionine content in Cnr mutants. Methionine supplementation rescues developmental and metabolic defects in Cnr mutant livers, suggesting a causal relationship between EC signaling, methionine deficiency and impaired liver development. The effect of Cnr on methionine metabolism is regulated by sterol regulatory element-binding transcription factors (Srebfs), as their overexpression rescues Cnr mutant liver phenotypes in a methionine-dependent manner. Our work describes a novel developmental role for EC signaling, whereby Cnr-mediated regulation of Srebfs and methionine metabolism impacts liver development and function.

  19. Liver expression quantitative trait loci: a foundation for pharmacogenomic research

    Directory of Open Access Journals (Sweden)

    Dylan eGlubb

    2012-08-01

    Full Text Available Expression quantitative trait loci (eQTL analysis can provide insights into the genetic regulation of gene expression at a genomic level and this information is proving extremely useful in many different areas of research. As a consequence of the role of the liver in drug metabolism and disposition, the study of eQTLs in primary human liver tissue could provide a foundation for pharmacogenomics. Thus far, four genome-wide eQTL studies have been performed using human livers. Many liver eQTLs have been found to be reproducible and a proportion of these may be specific to the liver. Already these data have been used to interpret and inform clinic genome-wide association studies, providing potential mechanistic evidence for clinical associations and identifying genes which may impact on clinical phenotypes. However, the utility of liver eQTL data has not yet been fully explored or realized in pharmacogenomics. As further liver eQTL research is undertaken, the genetic regulation of gene expression will become much better characterized and this knowledge will create a rational basis for the prospective pharmacogenomic study of many drugs.

  20. Operational handbook of the Bretby Maintainability Index

    Energy Technology Data Exchange (ETDEWEB)

    Rushworth, A.M.; Mason, S.; Talbot, C. (British Coal Corporation, Stanhope Bretby (United Kingdom). Technical Services and Research Executive, Ergonomics Branch)

    1994-01-01

    A substantial proportion of the injuries and costs in the mining industry, and in industry generally, occur during maintenance activities, particularly in work involving plant and machinery. A common thread linking the cause of these accidents and losses is a general deficiency in machine design, particularly the ergonomic aspects. This report concerns the Bretby Maintainability Index (BMI) which provides a comprehensive method of analysing and quantifying machinery maintainability in terms of health and safety and the financial implications associated with excessive downtime. The health and safety implications of poor machine design are discussed, as are the cost implications. The concept of the BMI is outlined and information on its application is given. Its detailed features are presented and guidance notes are provided.

  1. Maintainability Prediction and Analysis Study. Revision A

    Science.gov (United States)

    1978-07-01

    SS- 6b SECTION 1.0 INTRiODUCTION This document presents the results of a study to develop and document an improved maintainability prediction and...include operations on other RIs called out in the jth fault iscolation result . Tmujn Average time to perform the ruth corrective maintenance step for...of the study however, as the resulting time standards are used as Inputs In computing disassembly, interchange, and reassembly times for the

  2. Maintaining Multimedia Data in a Geospatial Database

    Science.gov (United States)

    2012-09-01

    ID (SRID). “The SRID is the spatial reference identification system. The SRID is part of a set of standards developed for cartography , surveying...in a GIS are stored in two-dimensional space, which adds to the complexities faced in simulating a databases’ workload when the data is three...benchmark testing. A. OVERVIEW In creating a GIS that maintains multimedia data, it is first important to note that the actual multimedia data is

  3. Maintaining Wolbachia in Cell-free Medium

    OpenAIRE

    Gamston, Courtney; Rasgon, Jason

    2007-01-01

    In this video protocol, procedures are demonstrated to (1) purify Wolbachia symbionts out of cultured mosquito cells, (2) use a fluorescent assay to ascertain the viability of the purified Wolbachia and (3) maintain the now extracellular Wolbachia in cell-free medium. Purified Wolbachia remain alive in the extracellular phase but do not replicate until re-inoculated into eukaryotic cells. Extracellular Wolbachia purified in this manner will remain viable for at least a week at ...

  4. Identification of a Locus for Autosomal Dominant Polycystic Liver Disease, on Chromosome 19p13.2-13.1

    OpenAIRE

    Reynolds, David M.; Falk, Cathy T.; Li, Airong; King, Bernard F.; Kamath, Patrick S.; Huston III, John; Shub, Clarence; Iglesias, Diana M.; Martin, Rodolfo S.; Pirson, Yves; Torres, Vicente E.; Somlo, Stefan

    2000-01-01

    Polycystic liver disease (PCLD) is characterized by the growth of fluid-filled cysts of biliary epithelial origin in the liver. Although the disease is often asymptomatic, it can, when severe, lead to complications requiring surgical therapy. PCLD is most often associated with autosomal dominant polycystic kidney disease (ADPKD); however, families with an isolated polycystic liver phenotype without kidney involvement have been described. The clinical presentation and histological features of ...

  5. Preservation of the liver for transplantation: Machine perfusion-based strategies for extended preservation and recovery

    NARCIS (Netherlands)

    Bruinsma, B.G.

    2015-01-01

    The field of liver transplantation remains burdened by a severe shortage of donor organs. An important limitation to the use of many livers is the ex vivo preservation of the organ, as maintaining the viability of the donor organ while outside the body is essential for successful transplantation. Th

  6. Frequency of the HFE C282Y and H63D mutations in Danish patients with clinical haemochromatosis initially diagnosed by phenotypic methods

    DEFF Research Database (Denmark)

    Milman, Nils; Koefoed, Pernille; Pedersen, Palle

    2003-01-01

    idiopathic haemochromatosis diagnosed by phenotypic methods (serum transferrin saturation, serum ferritin, liver biopsy and mobilisable body iron stores). In 32 unrelated patients, frozen blood samples were available for genetic analysis. In a subsequent series of 26 unrelated Danish patients, a phenotypic...

  7. Proteoglycans in liver cancer

    Science.gov (United States)

    Baghy, Kornélia; Tátrai, Péter; Regős, Eszter; Kovalszky, Ilona

    2016-01-01

    Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types. The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer. A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans. The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels. This article details and discusses the roles of syndecan-1, glypicans, agrin, perlecan, collagen XVIII/endostatin, endocan, serglycin, decorin, biglycan, asporin, fibromodulin, lumican, and versican in liver function. Specifically, glypicans, agrin, and versican play significant roles in the development of liver cancer. Conversely, the presence of decorin could potentially provide protective effects. PMID:26755884

  8. Cytokines and Liver Diseases

    Directory of Open Access Journals (Sweden)

    Herbert Tilg

    2001-01-01

    Full Text Available Cytokines are pleiotropic peptides produced by virtually every nucleated cell in the body. In most tissues, including the liver, constitutive production of cytokines is absent or minimal. There is increasing evidence that several cytokines mediate hepatic inflammation, apoptosis and necrosis of liver cells, cholestasis and fibrosis. Interestingly, the same mediators also mediate the regeneration of liver tissue after injury. Among the various cytokines, the proinflammatory cytokine tumour necrosis factor-alpha (TNF-a has emerged as a key factor in various aspects of liver disease, such as cachexia and/or cholestasis. Thus, antagonism of TNF-a and other injury-related cytokines in liver diseases merits evaluation as a treatment of these diseases. However, because the same cytokines are also necessary for the regeneration of the tissue after the liver has been injured, inhibition of these mediators might impair hepatic recovery. The near future will bring the exiting clinical challenge of testing new anticytokine strategies in various liver diseases.

  9. Proteoglycans in liver cancer.

    Science.gov (United States)

    Baghy, Kornélia; Tátrai, Péter; Regős, Eszter; Kovalszky, Ilona

    2016-01-07

    Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types. The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer. A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans. The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels. This article details and discusses the roles of syndecan-1, glypicans, agrin, perlecan, collagen XVIII/endostatin, endocan, serglycin, decorin, biglycan, asporin, fibromodulin, lumican, and versican in liver function. Specifically, glypicans, agrin, and versican play significant roles in the development of liver cancer. Conversely, the presence of decorin could potentially provide protective effects.

  10. Finding our way through phenotypes.

    Directory of Open Access Journals (Sweden)

    Andrew R Deans

    2015-01-01

    Full Text Available Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.

  11. Finding our way through phenotypes.

    Science.gov (United States)

    Deans, Andrew R; Lewis, Suzanna E; Huala, Eva; Anzaldo, Salvatore S; Ashburner, Michael; Balhoff, James P; Blackburn, David C; Blake, Judith A; Burleigh, J Gordon; Chanet, Bruno; Cooper, Laurel D; Courtot, Mélanie; Csösz, Sándor; Cui, Hong; Dahdul, Wasila; Das, Sandip; Dececchi, T Alexander; Dettai, Agnes; Diogo, Rui; Druzinsky, Robert E; Dumontier, Michel; Franz, Nico M; Friedrich, Frank; Gkoutos, George V; Haendel, Melissa; Harmon, Luke J; Hayamizu, Terry F; He, Yongqun; Hines, Heather M; Ibrahim, Nizar; Jackson, Laura M; Jaiswal, Pankaj; James-Zorn, Christina; Köhler, Sebastian; Lecointre, Guillaume; Lapp, Hilmar; Lawrence, Carolyn J; Le Novère, Nicolas; Lundberg, John G; Macklin, James; Mast, Austin R; Midford, Peter E; Mikó, István; Mungall, Christopher J; Oellrich, Anika; Osumi-Sutherland, David; Parkinson, Helen; Ramírez, Martín J; Richter, Stefan; Robinson, Peter N; Ruttenberg, Alan; Schulz, Katja S; Segerdell, Erik; Seltmann, Katja C; Sharkey, Michael J; Smith, Aaron D; Smith, Barry; Specht, Chelsea D; Squires, R Burke; Thacker, Robert W; Thessen, Anne; Fernandez-Triana, Jose; Vihinen, Mauno; Vize, Peter D; Vogt, Lars; Wall, Christine E; Walls, Ramona L; Westerfeld, Monte; Wharton, Robert A; Wirkner, Christian S; Woolley, James B; Yoder, Matthew J; Zorn, Aaron M; Mabee, Paula

    2015-01-01

    Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.

  12. Epigenetics in heart failure phenotypes

    Directory of Open Access Journals (Sweden)

    Alexander Berezin

    2016-12-01

    Full Text Available Chronic heart failure (HF is a leading clinical and public problem posing a higher risk of morbidity and mortality in different populations. HF appears to be in both phenotypic forms: HF with reduced left ventricular ejection fraction (HFrEF and HF with preserved left ventricular ejection fraction (HFpEF. Although both HF phenotypes can be distinguished through clinical features, co-morbidity status, prediction score, and treatment, the clinical outcomes in patients with HFrEF and HFpEF are similar. In this context, investigation of various molecular and cellular mechanisms leading to the development and progression of both HF phenotypes is very important. There is emerging evidence that epigenetic regulation may have a clue in the pathogenesis of HF. This review represents current available evidence regarding the implication of epigenetic modifications in the development of different HF phenotypes and perspectives of epigenetic-based therapies of HF.

  13. The human adult cardiomyocyte phenotype

    NARCIS (Netherlands)

    Bird, SD; Doevendans, PA; van Rooijen, MA; de la Riviere, AB; Hassink, RJ; Passier, R; Mummery, CL

    2003-01-01

    Aim: Determination of the phenotype of adult human atrial and ventricular myocytes based on gene expression and morphology. Methods: Atrial and ventricular cardiomyocytes were obtained from patients undergoing cardiac surgery using a modified isolation procedure. Myocytes were isolated and cultured

  14. EHR Big Data Deep Phenotyping

    National Research Council Canada - National Science Library

    L. J. Frey; L. Lenert; G. Lopez-Campos S. M. Meystre; G. K. Savova; K. C. Kipper-Schuler; J. F. Hurdle J. Zvárová; T. Dostálová; P. Hanzlíc∨ek; Z. Teuberová; M. Nagy; M. Pieš; M. Seydlová; Eliášová; H. Šimková Petra Knaup; Oliver Bott; Christian Kohl; Christian Lovis; Sebastian Garde

    2014-01-01

    Objectives: Given the quickening speed of discovery of variant disease drivers from combined patient genotype and phenotype data, the objective is to provide methodology using big data technology to support...

  15. Elastin in the Liver

    Directory of Open Access Journals (Sweden)

    Jiri Kanta

    2016-10-01

    Full Text Available A characteristic feature of liver cirrhosis is the accumulation of large amounts of connective tissue with the prevailing content of type I collagen. Elastin is a minor connective tissue component in normal liver but it is actively synthesized by hepatic stellate cells and portal fibroblasts in diseased liver. The accumulation of elastic fibers in later stages of liver fibrosis may contribute to the decreasing reversibility of the disease with advancing time. Elastin is formed by polymerization of tropoelastin monomers. It is an amorphous protein highly resistant to the action of proteases that forms the core of elastic fibers. Microfibrils surrounding the core are composed of fibrillins that bind a number of proteins involved in fiber formation. They include microfibril-associated glycoproteins (MAGPs, microfibrillar-associated proteins (MFAPs and fibulins. Lysyl oxidase (LOX and lysyl oxidase-like proteins (LOXLs are responsible for tropoelastin cross-linking and polymerization. TGF-β complexes attached to microfibrils release this cytokine and influence the behavior of the cells in the neighborhood. The role of TGF-β as the main profibrotic cytokine in the liver is well-known and the release of the cytokines of TGF-β superfamily from their storage in elastic fibers may affect the course of fibrosis. Elastic fibres are often studied in the tissues where they provide elasticity and resilience but their role is no longer viewed as purely mechanical. Tropoelastin, elastin polymer and elastin peptides resulting from partial elastin degradation influence fibroblastic and inflammatory cells as well as angiogenesis. A similar role may be performed by elastin in the liver. This article reviews the results of the research of liver elastic fibers on the backgound of the present knowledge of elastin biochemistry and physiology. The regulation of liver elastin synthesis and degradation may be important for the outcome of liver fibrosis.

  16. Mule duck "foie gras" shows different metabolic states according to its quality phenotype by using a proteomic approach.

    Science.gov (United States)

    François, Yoannah; Marie-Etancelin, Christel; Vignal, Alain; Viala, Didier; Davail, Stéphane; Molette, Caroline

    2014-07-23

    This study aimed at identifying the mechanisms implicated in "foie gras" quality variability through the study of the relationships between liver protein compositions and four liver quality phenotypes: liver weight, melting rate, and protein contents on crude or dry matter. Spots of soluble proteins were separated by bidimensional electrophoresis, and the relative abundance of proteins according to quality traits values was investigated. Twenty-three protein spots (19 unique identified proteins) showed different levels of abundance according to one or more of the traits' values. These abundance differences highlighted two groups of livers with opposite trends of abundance levels. Proteins of the first group, associated with low liver weight and melting rate, are involved in synthesis and anabolism processes, whereas proteins of the second group, associated with high liver weight and melting rate, are proteins involved in stress response. Altogether, these results highlight the variations in metabolic states underlying foie gras quality traits.

  17. Low Serum Hepcidin in Patients with Autoimmune Liver Diseases.

    Directory of Open Access Journals (Sweden)

    Aggeliki Lyberopoulou

    Full Text Available Hepcidin, a liver hormone, is important for both innate immunity and iron metabolism regulation. As dysfunction of the hepcidin pathway may contribute to liver pathology, we analysed liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases. Hepcidin mRNA levels were determined in liver biopsies obtained from 126 patients with HCV (n = 21, HBV (n = 23, autoimmune cholestatic disease (primary biliary cirrhosis and primary sclerosing cholangitis; PBC/PSC; n = 34, autoimmune hepatitis (AIH; n = 16 and non-alcoholic fatty liver disease (NAFLD; n = 32. Sera sampled on the biopsy day from the same patients were investigated for serum hepcidin levels. Hepatic hepcidin mRNA levels correlated positively with ferritin and negatively with serum γ-GT levels. However, no correlation was found between serum hepcidin and either ferritin or liver hepcidin mRNA. Both serum hepcidin and the serum hepcidin/ferritin ratio were significantly lower in AIH and PBC/PSC patients' sera compared to HBV, HCV or NAFLD (P<0.001 for each comparison and correlated negatively with serum ALP levels. PBC/PSC and AIH patients maintained low serum hepcidin during the course of their two-year long treatment. In summary, parallel determination of liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases shows that circulating hepcidin and its respective ratio to ferritin are significantly diminished in patients with autoimmune liver diseases. These novel findings, once confirmed by follow-up studies involving bigger size and better-matched disease subgroups, should be taken into consideration during diagnosis and treatment of autoimmune liver diseases.

  18. Establishment of animal model of dual liver transplantation in rat.

    Directory of Open Access Journals (Sweden)

    Ying Zhang

    Full Text Available The animal model of the whole-size and reduced-size liver transplantation in both rat and mouse has been successfully established. Because of the difficulties and complexities in microsurgical technology, the animal model of dual liver transplantation was still not established for twelve years since the first human dual liver transplantation has been made a success. There is an essential need to establish this animal model to lay a basic foundation for clinical practice. To study the physiological and histopathological changes of dual liver transplantation, "Y" type vein from the cross part between vena cava and two iliac of donor and "Y' type prosthesis were employed to recanalize portal vein and the bile duct between dual liver grafts and recipient. The dual right upper lobes about 45-50% of the recipient liver volume were taken as donor, one was orthotopically implanted at its original position, the other was rotated 180° sagitally and heterotopically positioned in the left upper quadrant. Microcirculation parameters, liver function, immunohistochemistry and survival were analyzed to evaluate the function of dual liver grafts. No significant difference in the hepatic microcirculatory flow was found between two grafts in the first 90 minutes after reperfusion. Light and electronic microscope showed the liver architecture was maintained without obvious features of cellular destruction and the continuity of the endothelium was preserved. Only 3 heterotopically positioned graft appeared patchy desquamation of endothelial cell, mitochondrial swelling and hepatocytes cytoplasmic vacuolization. Immunohistochemistry revealed there is no difference in hepatocyte activity and the ability of endothelia to contract and relax after reperfusion between dual grafts. Dual grafts made a rapid amelioration of liver function after reperfusion. 7 rats survived more than 7 days with survival rate of 58.3.%. Using "Y" type vein and bile duct prosthesis, we

  19. Low Serum Hepcidin in Patients with Autoimmune Liver Diseases.

    Science.gov (United States)

    Lyberopoulou, Aggeliki; Chachami, Georgia; Gatselis, Nikolaos K; Kyratzopoulou, Eleni; Saitis, Asterios; Gabeta, Stella; Eliades, Petros; Paraskeva, Efrosini; Zachou, Kalliopi; Koukoulis, George K; Mamalaki, Avgi; Dalekos, George N; Simos, George

    2015-01-01

    Hepcidin, a liver hormone, is important for both innate immunity and iron metabolism regulation. As dysfunction of the hepcidin pathway may contribute to liver pathology, we analysed liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases. Hepcidin mRNA levels were determined in liver biopsies obtained from 126 patients with HCV (n = 21), HBV (n = 23), autoimmune cholestatic disease (primary biliary cirrhosis and primary sclerosing cholangitis; PBC/PSC; n = 34), autoimmune hepatitis (AIH; n = 16) and non-alcoholic fatty liver disease (NAFLD; n = 32). Sera sampled on the biopsy day from the same patients were investigated for serum hepcidin levels. Hepatic hepcidin mRNA levels correlated positively with ferritin and negatively with serum γ-GT levels. However, no correlation was found between serum hepcidin and either ferritin or liver hepcidin mRNA. Both serum hepcidin and the serum hepcidin/ferritin ratio were significantly lower in AIH and PBC/PSC patients' sera compared to HBV, HCV or NAFLD (Pserum ALP levels. PBC/PSC and AIH patients maintained low serum hepcidin during the course of their two-year long treatment. In summary, parallel determination of liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases shows that circulating hepcidin and its respective ratio to ferritin are significantly diminished in patients with autoimmune liver diseases. These novel findings, once confirmed by follow-up studies involving bigger size and better-matched disease subgroups, should be taken into consideration during diagnosis and treatment of autoimmune liver diseases.

  20. Spontaneous focal activation of invariant natural killer T (iNKT cells in mouse liver and kidney

    Directory of Open Access Journals (Sweden)

    Zeng Jia

    2010-11-01

    Full Text Available Abstract Background Invariant natural killer T (iNKT cells differ from other T cells by their hyperactive effector T-cell status, in addition to the expression of NK lineage receptors and semi-invariant T-cell receptors. It is generally agreed that the immune phenotype of iNKT cells is maintained by repeated activation in peripheral tissues although no explicit evidence for such iNKT cell activity in vivo has so far been reported. Results We used an interferon (IFN-γ-inducible cytoplasmic protein, Irga6, as a histological marker for local IFN-γ production. Irga6 was intensely expressed in small foci of liver parenchymal cells and kidney tubular epithelium. Focal Irga6 expression was unaffected by germ-free status or loss of TLR signalling and was totally dependent on IFN-γ secreted by T cells in the centres of expression foci. These were shown to be iNKT cells by diagnostic T cell receptor usage and their activity was lost in both CD1 d and Jα-deficient mice. Conclusions This is the first report that supplies direct evidence for explicit activation events of NKT cells in vivo and raises issues about the triggering mechanism and consequences for immune functions in liver and kidney.

  1. Experimental obstructive cholestasis: the wound-like inflammatory liver response

    Directory of Open Access Journals (Sweden)

    Aller María-Angeles

    2008-11-01

    Full Text Available Abstract Obstructive cholestasis causes hepatic cirrhosis and portal hypertension. The pathophysiological mechanisms involved in the development of liver disease are multiple and linked. We propose grouping these mechanisms according to the three phenotypes mainly expressed in the interstitial space in order to integrate them. Experimental extrahepatic cholestasis is the model most frequently used to study obstructive cholestasis. The early liver interstitial alterations described in these experimental models would produce an ischemia/reperfusion phenotype with oxidative and nitrosative stress. Then, the hyperexpression of a leukocytic phenotype, in which Kupffer cells and neutrophils participate, would induce enzymatic stress. And finally, an angiogenic phenotype, responsible for peribiliary plexus development with sinusoidal arterialization, occurs. In addition, an intense cholangiocyte proliferation, which acquires neuroendocrine abilities, stands out. This histopathological finding is also associated with fibrosis. It is proposed that the sequence of these inflammatory phenotypes, perhaps with a trophic meaning, ultimately produces a benign tumoral biliary process – although it poses severe hepatocytic insufficiency. Moreover, the persistence of this benign tumor disease would induce a higher degree of dedifferentiation and autonomy and, therefore, its malign degeneration.

  2. Imaging of liver cancer

    Institute of Scientific and Technical Information of China (English)

    Ben Ariff; Claire R Lloyd; Sameer Khan; Mohamed Shariff; Andrew V Thillainayagam; Devinder S Bansi; Shahid A Khan; Simon D Taylor-Robinson; Adrian KP Lim

    2009-01-01

    Improvements in imaging technology allow exploitation of the dual blood supply of the liver to aid in the identi-fication and characterisation of both malignant and benign liver lesions. Imaging techniques available include contrast enhanced ultrasound, computed tomography and magnetic resonance imaging. This review discusses the application of several imaging techniques in the diagnosis and staging of both hepatocellular carcinoma and cholangiocarcinoma and outlines certain characteristics of benign liver lesions. The advantages of each imaging technique are highlighted, while underscoring the potential pitfalls and limitations of each imaging modality.

  3. [Cysts of the liver

    DEFF Research Database (Denmark)

    Hillingso, J.G.; Kirkegaard, P.

    2008-01-01

    Cysts of the liver are discovered in connection with a scope of diseases ranging from simple, infectious, or parasitic to neoplastic cysts. Symptoms, paraclinical, radiological and diagnostic characteristics are described with emphasis on ruling out malignancy. The treatment options from ultrasound...... guided drainage to resections and liver transplantation are discussed. It is concluded that up to 25% of cysts must be treated surgically, because recurrence after percutaneous or laparoscopic treatment is between 5% and 71%, and only resection or liver transplantation are curative Udgivelsesdato: 2008/4/14...

  4. The digital revolution in phenotyping

    Science.gov (United States)

    Oellrich, Anika; Collier, Nigel; Groza, Tudor; Rebholz-Schuhmann, Dietrich; Shah, Nigam; Bodenreider, Olivier; Boland, Mary Regina; Georgiev, Ivo; Liu, Hongfang; Livingston, Kevin; Luna, Augustin; Mallon, Ann-Marie; Manda, Prashanti; Robinson, Peter N.; Rustici, Gabriella; Simon, Michelle; Wang, Liqin; Winnenburg, Rainer; Dumontier, Michel

    2016-01-01

    Phenotypes have gained increased notoriety in the clinical and biological domain owing to their application in numerous areas such as the discovery of disease genes and drug targets, phylogenetics and pharmacogenomics. Phenotypes, defined as observable characteristics of organisms, can be seen as one of the bridges that lead to a translation of experimental findings into clinical applications and thereby support ‘bench to bedside’ efforts. However, to build this translational bridge, a common and universal understanding of phenotypes is required that goes beyond domain-specific definitions. To achieve this ambitious goal, a digital revolution is ongoing that enables the encoding of data in computer-readable formats and the data storage in specialized repositories, ready for integration, enabling translational research. While phenome research is an ongoing endeavor, the true potential hidden in the currently available data still needs to be unlocked, offering exciting opportunities for the forthcoming years. Here, we provide insights into the state-of-the-art in digital phenotyping, by means of representing, acquiring and analyzing phenotype data. In addition, we provide visions of this field for future research work that could enable better applications of phenotype data. PMID:26420780

  5. Chronic subordination stress selectively downregulates the insulin signaling pathway in liver and skeletal muscle but not in adipose tissue of male mice.

    Science.gov (United States)

    Sanghez, Valentina; Cubuk, Cankut; Sebastián-Leon, Patricia; Carobbio, Stefania; Dopazo, Joaquin; Vidal-Puig, Antonio; Bartolomucci, Alessandro

    2016-01-01

    Chronic stress has been associated with obesity, glucose intolerance, and insulin resistance. We developed a model of chronic psychosocial stress (CPS) in which subordinate mice are vulnerable to obesity and the metabolic-like syndrome while dominant mice exhibit a healthy metabolic phenotype. Here we tested the hypothesis that the metabolic difference between subordinate and dominant mice is associated with changes in functional pathways relevant for insulin sensitivity, glucose and lipid homeostasis. Male mice were exposed to CPS for four weeks and fed either a standard diet or a high-fat diet (HFD). We first measured, by real-time PCR candidate genes, in the liver, skeletal muscle, and the perigonadal white adipose tissue (pWAT). Subsequently, we used a probabilistic analysis approach to analyze different ways in which signals can be transmitted across the pathways in each tissue. Results showed that subordinate mice displayed a drastic downregulation of the insulin pathway in liver and muscle, indicative of insulin resistance, already on standard diet. Conversely, pWAT showed molecular changes suggestive of facilitated fat deposition in an otherwise insulin-sensitive tissue. The molecular changes in subordinate mice fed a standard diet were greater compared to HFD-fed controls. Finally, dominant mice maintained a substantially normal metabolic and molecular phenotype even when fed a HFD. Overall, our data demonstrate that subordination stress is a potent stimulus for the downregulation of the insulin signaling pathway in liver and muscle and a major risk factor for the development of obesity, insulin resistance, and type 2 diabetes mellitus.

  6. Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy

    Science.gov (United States)

    Kristiansen, Maria Nicoline Baandrup; Veidal, Sanne Skovgård; Rigbolt, Kristoffer Tobias Gustav; Tølbøl, Kirstine Sloth; Roth, Jonathan David; Jelsing, Jacob; Vrang, Niels; Feigh, Michael

    2016-01-01

    AIM: To characterize development of diet-induced nonalcoholic steatohepatitis (NASH) by performing liver biopsy in wild-type and genetically obese mice. METHODS: Male wild-type C57BL/6J (C57) mice (DIO-NASH) and male Lepob/Lepob (ob/ob) mice (ob/ob-NASH) were maintained on a diet high in trans-fat (40%), fructose (22%) and cholesterol (2%) for 26 and 12 wk, respectively. A normal chow diet served as control in C57 mice (lean chow) and ob/ob mice (ob/ob chow). After the diet-induction period, mice were liver biopsied and a blinded histological assessment of steatosis and fibrosis was conducted. Mice were then stratified into groups counterbalanced for steatosis score and fibrosis stage and continued on diet and to receive daily PO dosing of vehicle for 8 wk. Global gene expression in liver tissue was assessed by RNA sequencing and bioinformatics. Metabolic parameters, plasma liver enzymes and lipids (total cholesterol, triglycerides) as well as hepatic lipids and collagen content were measured by biochemical analysis. Non-alcoholic fatty liver disease activity score (NAS) (steatosis/inflammation/ballooning degeneration) and fibrosis were scored. Steatosis and fibrosis were also quantified using percent fractional area. RESULTS: Diet-induction for 26 and 12 wk in DIO-NASH and ob/ob-NASH mice, respectively, elicited progressive metabolic perturbations characterized by increased adiposity, total cholesterol and elevated plasma liver enzymes. The diet also induced clear histological features of NASH including hepatosteatosis and fibrosis. Overall, the metabolic NASH phenotype was more pronounced in ob/ob-NASH vs DIO-NASH mice. During the eight week repeated vehicle dosing period, the metabolic phenotype was sustained in DIO-NASH and ob/ob-NASH mice in conjunction with hepatomegaly and increased hepatic lipids and collagen accumulation. Histopathological scoring demonstrated significantly increased NAS of DIO-NASH mice (0 vs 4.7 ± 0.4, P < 0.001 compared to lean chow

  7. Liver Transplant: Nutrition

    Science.gov (United States)

    ... include poultry, eggs, fish, tofu, and soy protein. Low Sodium -- Symptoms of advanced liver disease include excess fluid ... it is very important to stick to a low sodium diet, especially when these symptoms start to develop. ...

  8. American Liver Foundation

    Science.gov (United States)

    ... organ, eye and tissue donation. Learn more about organ donation . Locate a Specialist Find a medical professional nearby ... Help us spread the word about liver disease, organ donation, and the ALF- amplifying the message through social ...

  9. [Nutrition and liver failure].

    Science.gov (United States)

    Plauth, M

    2013-06-01

    In the critically ill liver patient, nutrition support is not very different from that given for other illnesses. In hyperacute liver failure, nutrition support is of less importance than in the other subtypes of acute liver failure that take a more protracted course. Nasoenteral tube feeding using a polymeric standard formula should be the first-line approach, while parenteral nutrition giving glucose, fat, amino acids, vitamins, and trace elements is initiated when enteral nutrition is insufficient or impracticable. In chronic liver disease, notably cirrhosis, there is frequently protein malnutrition indicating a poor prognosis and requiring immediate initiation of nutrition support. Enteral nutrition ensuring an adequate provision of energy and protein should be preferred. Particular care should be taken to avoid refeeding syndrome and to treat vitamin and trace element deficiency.

  10. 492 Review Liver

    African Journals Online (AJOL)

    Marinda

    2009-11-26

    Nov 26, 2009 ... to define clinical and blood test predictors for major bleeding during liver ... A recent meta-analysis of randomised controlled trials comparing these devices to .... These are either fibrin sealants that mimic coagulation, agents.

  11. [Wilson disease: liver form].

    Science.gov (United States)

    Guerra Montero, Luis; Ortega Álvarez, Félix; Sumire Umeres, Julia; Cok García, Jaime

    2015-01-01

    Wilson disease (WD) is a disorder of copper metabolism that is inherited as an autosomal recessive, which produces toxic copper accumulation mainly in the liver and brain, in general has two ways presentation, liver at early ages and neurological in later ages. We present the case of a female patient of 21 years diagnosed of WD in liver cirrhosis that started with an edematous ascites without any neurological symptoms despite the age. Their laboratory studies showed decrease in serum ceruloplasmin and high cupruria within 24 hours of the disease , characteristic data of WD. Although WD is not a common disease should be suspected in all chronic liver disease of unknown etiology with negative viral markers and autoimmunity with or without neurological manifestations as soon as posible and starting treatment with copper chelating mainly leads to a substantial improvement the prognosis of these patients.

  12. Pediatric liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Marco Spada; Silvia Riva; Giuseppe Maggiore; Davide Cintorino; Bruno Gridelli

    2009-01-01

    In previous decades, pediatric liver transplantation has become a state-of-the-art operation with excellent success and limited mortality. Graft and patient survival have continued to improve as a result of improvements in medical, surgical and anesthetic management, organ availability, immunosuppression, and identification and treatment of postoperative complications. The utilization of split-liver grafts and living-related donors has provided more organs for pediatric patients. Newer immunosuppression regimens, including induction therapy, have had a significant impact on graft and patient survival. Future developments of pediatric liver transplantation will deal with long-term followup, with prevention of immunosuppression-related complications and promotion of as normal growth as possible. This review describes the state-of-the-art in pediatric liver transplantation.

  13. [Diabetes in liver cirrhosis].

    Science.gov (United States)

    García-Compeán, Diego; Jáquez-Quintana, Joel O; González-González, José A; Lavalle-González, Fernando J; Villarreal-Pérez, Jesús Z; Maldonado-Garza, Hector J

    2013-01-01

    The prevalence of overt diabetes mellitus (DM) in liver cirrhosis is about 30%. However, DM or impaired glucose tolerance can be observed in 90% after an oral glucose tolerance test in patients with normal fasting plasma glucose. Type 2 DM may produce cirrhosis, whereas DM may be a complication of cirrhosis. The latter is known as «hepatogenous diabetes». Overt and subclinical DM is associated with liver complications and death in cirrhotic patients. Treating diabetes is difficult in cirrhotic patients because of the metabolic impairments due to liver disease and because the most appropriate pharmacologic treatment has not been defined. It is also unknown if glycemic control with hypoglycemic agents has any impact on the course of the liver disease. Copyright © 2013 Elsevier España, S.L. y AEEH y AEG. All rights reserved.

  14. Fusobacterium Liver Abscess

    Directory of Open Access Journals (Sweden)

    Ben D. Buelow

    2013-11-01

    Full Text Available Fusobacterium is well characterized as an oropharyngeal pathogen that may induce a septic thrombophlebitis by direct extension of abscess into an adjacent neck vessel (Lemierre's syndrome; its potential for visceral abscess formation, however, remains under-recognized. A 65-year-old man with a recent history of multiple rim-enhancing liver lesions presented to the emergency room with fever and abdominal pain. Based on interval increase in the size of the lesions, abscess was suspected. A liver biopsy was performed, and although no organism could be identified on routine microscopy, Warthin-Starry stain revealed Gram-negative bacilli consistent with an anaerobic Fusobacterium species as the underlying etiology of liver abscess formation. Subsequent anaerobic culture results confirmed the diagnosis. This case highlights the importance of consideration for Fusobacterium infection in the setting of liver abscess if anaerobic organisms have not yet been excluded on initial culture evaluation.

  15. Autoimmune liver diseases

    Institute of Scientific and Technical Information of China (English)

    Pietro Invernizzi; Ian R Mackay

    2008-01-01

    The liver was one of the earliest recognized sites among autoimmune diseases yet autoimmune hepatitis,primary biliary cirrhosis,primary sclerosing cholangitis,and their overlap forms,are still problematic in diagnosis and causation.The contributions herein comprise 'pairs of articles' on clinical characteristics,and concepts of etiopathogenesis,for each of the above diseases,together with childhood autoimmune liver disease,overlaps,interpretations of diagnostic serology,and liver transplantation.This issue is timely,since we are witnessing an ever increasing applicability of immunology to a wide variety of chronic diseases,hepatic and non-hepatic,in both developed and developing countries.The 11 invited expert review articles capture the changing features over recent years of the autoimmune liver diseases,the underlying immunomolecular mechanisms of development,the potent albeit still unexplained genetic influences,the expanding repertoire of immunoserological diagnostic markers,and the increasingly effective therapeutic possibilities.

  16. Mice with humanized liver endothelium

    NARCIS (Netherlands)

    el Filali, E.

    2014-01-01

    The only curative treatment option for a large proportion of patients suffering from a liver disorder is liver transplantation. The use of ex vivo genetically modified autologous liver cells instead of whole liver transplantation could overcome the problem of donor scarcity. Even though clinical

  17. Antioxidant supplements for liver diseases

    DEFF Research Database (Denmark)

    Bjelakovic, Goran; Gluud, Lise Lotte; Nikolova, Dimitrinka

    2011-01-01

    Several liver diseases have been associated with oxidative stress. Accordingly, antioxidants have been suggested as potential therapeutics for various liver diseases. The evidence supporting these suggestions is equivocal.......Several liver diseases have been associated with oxidative stress. Accordingly, antioxidants have been suggested as potential therapeutics for various liver diseases. The evidence supporting these suggestions is equivocal....

  18. Mice with humanized liver endothelium

    NARCIS (Netherlands)

    el Filali, E.

    2014-01-01

    The only curative treatment option for a large proportion of patients suffering from a liver disorder is liver transplantation. The use of ex vivo genetically modified autologous liver cells instead of whole liver transplantation could overcome the problem of donor scarcity. Even though clinical tri

  19. Identifying crucial parameter correlations maintaining bursting activity.

    Directory of Open Access Journals (Sweden)

    Anca Doloc-Mihu

    2014-06-01

    Full Text Available Recent experimental and computational studies suggest that linearly correlated sets of parameters (intrinsic and synaptic properties of neurons allow central pattern-generating networks to produce and maintain their rhythmic activity regardless of changing internal and external conditions. To determine the role of correlated conductances in the robust maintenance of functional bursting activity, we used our existing database of half-center oscillator (HCO model instances of the leech heartbeat CPG. From the database, we identified functional activity groups of burster (isolated neuron and half-center oscillator model instances and realistic subgroups of each that showed burst characteristics (principally period and spike frequency similar to the animal. To find linear correlations among the conductance parameters maintaining functional leech bursting activity, we applied Principal Component Analysis (PCA to each of these four groups. PCA identified a set of three maximal conductances (leak current, [Formula: see text]Leak; a persistent K current, [Formula: see text]K2; and of a persistent Na+ current, [Formula: see text]P that correlate linearly for the two groups of burster instances but not for the HCO groups. Visualizations of HCO instances in a reduced space suggested that there might be non-linear relationships between these parameters for these instances. Experimental studies have shown that period is a key attribute influenced by modulatory inputs and temperature variations in heart interneurons. Thus, we explored the sensitivity of period to changes in maximal conductances of [Formula: see text]Leak, [Formula: see text]K2, and [Formula: see text]P, and we found that for our realistic bursters the effect of these parameters on period could not be assessed because when varied individually bursting activity was not maintained.

  20. SOCS2 Balances Metabolic and Restorative Requirements during Liver Regeneration.

    Science.gov (United States)

    Masuzaki, Ryota; Zhao, Sophia; Valerius, M Todd; Tsugawa, Daisuke; Oya, Yuki; Ray, Kevin C; Karp, Seth J

    2016-02-12

    After significant injury, the liver must maintain homeostasis during the regenerative process. We hypothesized the existence of mechanisms to limit hepatocyte proliferation after injury to maintain metabolic and synthetic function. A screen for candidates revealed suppressor of cytokine signaling 2 (SOCS2), an inhibitor of growth hormone (GH) signaling, was strongly induced after partial hepatectomy. Using genetic deletion and administration of various factors we investigated the role of SOCS2 during liver regeneration. SOCS2 preserves liver function by restraining the first round of hepatocyte proliferation after partial hepatectomy by preventing increases in growth hormone receptor (GHR) via ubiquitination, suppressing GH pathway activity. At later times, SOCS2 enhances hepatocyte proliferation by modulating a decrease in serum insulin-like growth factor 1 (IGF-1) that allows GH release from the pituitary. SOCS2, therefore, plays a dual role in modulating the rate of hepatocyte proliferation. In particular, this is the first demonstration of an endogenous mechanism to limit hepatocyte proliferation after injury.

  1. Acute liver failure

    DEFF Research Database (Denmark)

    Larsen, Fin Stolze; Bjerring, Peter Nissen

    2011-01-01

    Acute liver failure (ALF) results in a multitude of serious complications that often lead to multi-organ failure. This brief review focuses on the pathophysiological processes in ALF and how to manage these.......Acute liver failure (ALF) results in a multitude of serious complications that often lead to multi-organ failure. This brief review focuses on the pathophysiological processes in ALF and how to manage these....

  2. Liver and Biliary System

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008546 Effects of gene-transfected bone marrow-derived liver stem cell transplantation on accumulation of extracellular matrix in rats with liver fibrosis.SUN Chao(孙超),et al.Dept Gastroenterol,Xinhua Hosp,Shanghai Jiaotong Univ,Shanghai 200092.Natl Med J China 2008;88(38):2685-2689. Objective To explore the effects of urokinase-type plasminogen activator(uPA)gene modified bone marrow-derived stem cell(BDLSC)

  3. Influence of the bacterial phenotypes on the clinical manifestations in Klebsiella pneumoniae bacteremia patients: A retrospective cohort study.

    Science.gov (United States)

    Togawa, Atsushi; Toh, Hiromi; Onozawa, Kyoko; Yoshimura, Michinobu; Tokushige, Chiemi; Shimono, Nobuyuki; Takata, Tohru; Tamura, Kazuo

    2015-07-01

    Ninety-four episodes of Klebsiella pneumoniae bloodstream infection were identified at a university hospital in Japan. After excluding extended-spectrum beta lactamase-producing strains, 83 blood isolates from these patients were assayed in terms of their bacterial phenotypes such as the mucoid and hypermucoviscosity phenotypes. Bacterial phenotypes were correlated with the patients' clinical manifestations. The hypermucoviscosity phenotype was significantly associated with septic shock at the onset of infections (odds ratio, 15.92; 95% confidence interval, 1.27-468.12), but was not associated with liver abscess formation. Mortality was determined by the presence of septic shock. RmpA gene was associated with the induction of the hypermucoviscosity phenotype. These results reveal unique roles of bacterial phenotypes on the patient's clinical condition in K. pneumoniae bacteremia.

  4. LIVER TRANSPLANTATION AND HBV INFECTION

    Directory of Open Access Journals (Sweden)

    O. I. Andreytseva

    2009-01-01

    Full Text Available The paper describes the modern approaches in treatment of hepatitis B virus (HBV-infected patients who underwent liver transplantation. The patients with HBV liver cirrhosis and waiting for orthotopic liver transplantation (OLT have to receive long-term therapy with nucleos(tide analogs right up to liver transplantation. The paper discuss the different schemes of prophylaxis of recurrent HBV infection during post-transplantation and specific treatment of HBV infection after liver transplantation as well as possibilities of orthotopic liver transplantation for patients with liver cancer. 

  5. Store operations to maintain cache coherence

    Energy Technology Data Exchange (ETDEWEB)

    Evangelinos, Constantinos; Nair, Ravi; Ohmacht, Martin

    2017-09-12

    In one embodiment, a computer-implemented method includes encountering a store operation during a compile-time of a program, where the store operation is applicable to a memory line. It is determined, by a computer processor, that no cache coherence action is necessary for the store operation. A store-without-coherence-action instruction is generated for the store operation, responsive to determining that no cache coherence action is necessary. The store-without-coherence-action instruction specifies that the store operation is to be performed without a cache coherence action, and cache coherence is maintained upon execution of the store-without-coherence-action instruction.

  6. Store operations to maintain cache coherence

    Energy Technology Data Exchange (ETDEWEB)

    Evangelinos, Constantinos; Nair, Ravi; Ohmacht, Martin

    2017-08-01

    In one embodiment, a computer-implemented method includes encountering a store operation during a compile-time of a program, where the store operation is applicable to a memory line. It is determined, by a computer processor, that no cache coherence action is necessary for the store operation. A store-without-coherence-action instruction is generated for the store operation, responsive to determining that no cache coherence action is necessary. The store-without-coherence-action instruction specifies that the store operation is to be performed without a cache coherence action, and cache coherence is maintained upon execution of the store-without-coherence-action instruction.

  7. Storage methods to maintain a tulip collection

    OpenAIRE

    Bonnier, F.J.M.; Eikelboom, W.; Tuyl, van, J.M.

    1997-01-01

    Collections of tulip genotypes are maintained by yearly planting, harvesting and storage of the bulbs. To optimise the maintenance, two methods were examined for their suitability to store bulbs for one or more growing seasons. Method 1: bulbs were stored after flower development at -2 °C. Method 2: bulbs were stored before the start of flower development at -0.5 °C, followed by a temperature regime of 4 weeks 25 °C, 6 weeks 20 °C and 16 weeks 5 °C, for development of sprouts. With the first ...

  8. Take Control of Maintaining Your Mac

    CERN Document Server

    Kissell, Joe

    2009-01-01

    Keep your Mac running smoothly with our easy maintenance program! Regular maintenance is necessary to avoid problems and to ensure your Mac runs at peak performance, but it's hard to know what to do and when to do it. Best-selling author Joe Kissell has now applied his commonsense approach to the task of maintaining your Mac, whether you use Tiger or Leopard! Learn how to start on the right foot; what you should do daily, weekly, monthly, and yearly; and how to prepare for Mac OS X updates. Joe even explains how to monitor your Mac's health and debunks common panaceas. Read this book to lea

  9. Cloning and characterization of a mouse liver-specific gene mfrep-1, upregulated in liver regeneration

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Human fibrinogen-related protein-1/liver fibrinogen-related protein-1 (HFREP-1/LFIRE-1), a liver-specificprotein, is a member of fibrinogen superfamily that exerts various biological activities. However, the func-tion of HFREP-1/LFIRE-1 in liver remains unknown. Here we isolated its mouse ortholog gene-mousefibrinogen-related protein-1 (mfrep-1), which encoded 314 amino acids, exhibiting 80.4% similarity toHFREP-1/LFIRE-1. Northern blot analysis revealed that 1.2-kb mfrep-1 mRNA was detected selectivelyin mouse liver. To explore the function of MFREP-1, we examined the levels of mfrep-1 mRNA duringregeneration after 70% partial hepatectomy (PHx) in mice. mfrep-1 mRNA increased in the regeneratingliver and reached the first shoulder peak at 2-4 h after PHx. Cycloheximide pretreatment could suppress theinduction of mfrep-1, indicating the up-regulation of this gene need de novo protein synthesis. Its mRNAcontinued to elevate at 6 h thereafter and reached the second peak at 24 h. The enhanced expression ofmfrep-1 maintained high until 72 h and then declined slowly to the basal level. Immunohistochemistryassessment confirmed the up-regulated expression of MFREP-1 protein in parenchymal cells during liverregeneration. These data suggested that MFREP-1 might play an important role in liver regeneration andbe involved in the regulation of cell growth.

  10. Safety and Yield of Diagnostic ERCP in Liver Transplant Patients with Abnormal Liver Function Tests

    Directory of Open Access Journals (Sweden)

    Jayapal Ramesh

    2014-01-01

    Full Text Available Background. Abnormal liver enzymes postorthotopic liver transplant (OLT may indicate significant biliary pathology or organ rejection. There is very little known in the literature regarding the current role of diagnostic ERCP in this scenario. Aim. To review the utility of diagnostic ERCP in patients presenting with abnormal liver function tests in the setting of OLT. Methods. A retrospective review of diagnostic ERCPs in patients with OLT from 2002 to 2013 from a prospectively maintained, IRB approved database. Results. Of the 474 ERCPs performed in OLT patients, 210 (44.3%; 95% CI 39.8–48.8 were performed for abnormal liver function tests during the study period. Majority of patients were Caucasian (83.8%, male (62.4% with median age of 55 years (IQR 48–62 years. Biliary cannulation was successful in 99.6% of cases and findings included stricture in 45 (21.4 %; biliary stones/sludge in 23 (11%; biliary dilation alone in 31 (14.8%; and normal in 91 (43.3%. Three (1.4% patients developed mild, self-limiting pancreatitis; one patient (0.5% developed cholangitis and two (1% had postsphincterotomy bleeding. Multivariate analyses showed significant association between dilated ducts on imaging with a therapeutic outcome. Conclusion. Diagnostic ERCP in OLT patients presenting with liver function test abnormalities is safe and frequently therapeutic.

  11. Split liver transplantation.

    Science.gov (United States)

    Yersiz, H; Cameron, A M; Carmody, I; Zimmerman, M A; Kelly, B S; Ghobrial, R M; Farmer, D G; Busuttil, R W

    2006-03-01

    Seventy-five thousand Americans develop organ failure each year. Fifteen percent of those on the list for transplantation die while waiting. Several possible mechanisms to expand the organ pool are being pursued including the use of extended criteria donors, living donation, and split deceased donor transplants. Cadaveric organ splitting results from improved understanding of the surgical anatomy of the liver derived from Couinaud. Early efforts focused on reduced-liver transplantation (RLT) reported by both Bismuth and Broelsch in the mid-1980s. These techniques were soon modified to create both a left lateral segment graft appropriate for a pediatric recipient and a right trisegment for an appropriately sized adult. Techniques of split liver transplantation (SLT) were also modified to create living donor liver transplantation. Pichlmayr and Bismuth reported successful split liver transplantation in 1989 and Emond reported a larger series of nine split procedures in 1990. Broelsch and Busuttil described a technical modification in which the split was performed in situ at the donor institution with surgical division completed in the heart beating cadaveric donor. In situ splitting reduces cold ischemia, simplifies identification of biliary and vascular structures, and reduces reperfusion hemorrhage. However, in situ splits require specialized skills, prolonged operating room time, and increased logistical coordination at the donor institution. At UCLA over 120 in situ splits have been performed and this technique is the default when an optimal donor is available. Split liver transplantation now accounts for 10% of adult transplantations at UCLA and 40% of pediatric transplantations.

  12. Liver disease and malnutrition.

    Science.gov (United States)

    Purnak, Tugrul; Yilmaz, Yusuf

    2013-08-01

    Patients with hepatic disorders are exceptionally vulnerable to developing malnutrition because of the key role played by the liver in regulating the nutritional state and the energy balance. Moreover, the presence of chronic liver disorders could reduce the appetite and thus influence the nutrient intake. Poor nutritional status has been shown in various patient groups with hepatic disorders, and particularly in patients with alcoholic cirrhosis who are at high nutritional risk. It is well established that malnourished patients with liver diseases generally have a higher risk of developing adverse clinical outcomes and increased healthcare costs. Nutrition screening with the Subjective Global Assessment and anthropometric measurements are an important first step in the early identification of malnutrition and initiates the whole nutrition care process. It is therefore important for appropriate nutrition policies and protocols to be implemented so that all patients with chronic liver diseases are monitored closely from a nutritional standpoint. Early and evidence-based nutritional interventions are eagerly needed to minimize the nutritional decline associated with chronic liver disorders and ultimately improve the prognosis of such patients. This review includes a comprehensive analysis of methods to identify malnutrition in patients with chronic liver diseases as well as the extent and impact of the malnutrition problem in selected patient populations.

  13. Syndecan-1 is required to maintain intradermal fat and prevent cold stress.

    Directory of Open Access Journals (Sweden)

    Ildiko Kasza

    2014-08-01

    Full Text Available Homeostatic temperature regulation is fundamental to mammalian physiology and is controlled by acute and chronic responses of local, endocrine and nervous regulators. Here, we report that loss of the heparan sulfate proteoglycan, syndecan-1, causes a profoundly depleted intradermal fat layer, which provides crucial thermogenic insulation for mammals. Mice without syndecan-1 enter torpor upon fasting and show multiple indicators of cold stress, including activation of the stress checkpoint p38α in brown adipose tissue, liver and lung. The metabolic phenotype in mutant mice, including reduced liver glycogen, is rescued by housing at thermoneutrality, suggesting that reduced insulation in cool temperatures underlies the observed phenotypes. We find that syndecan-1, which functions as a facultative lipoprotein uptake receptor, is required for adipocyte differentiation in vitro. Intradermal fat shows highly dynamic differentiation, continuously expanding and involuting in response to hair cycle and ambient temperature. This physiology probably confers a unique role for Sdc1 in this adipocyte sub-type. The PPARγ agonist rosiglitazone rescues Sdc1-/- intradermal adipose tissue, placing PPARγ downstream of Sdc1 in triggering adipocyte differentiation. Our study indicates that disruption of intradermal adipose tissue development results in cold stress and complex metabolic pathology.

  14. Phenotypic Differentiation Is Associated with Gender Plasticity and Its Responsive Delay to Environmental Changes in Alternanthera philoxeroides – Phenotypic Differentiation in Alligator Weed

    Science.gov (United States)

    Liu, Wei; Deng, Ru-Fang; Liu, Wen-Ping; Wang, Zhang-Ming; Ye, Wan-Hui; Wang, Lan-Ying; Cao, Hong-Lin; Shen, Hao

    2011-01-01

    Phenotypic plasticity is common in many taxa, and it may increase an organism's fitness in heterogeneous environments. However, in some cases, the frequency of environmental changes can be faster than the ability of the individual to produce new adaptive phenotypes. The importance of such a time delay in terms of individual fitness and species adaptability has not been well studied. Here, we studied gender plasticity of Alternanthera philoxeroides to address this issue through a reciprocal transplant experiment. We observed that the genders of A. philoxeroides were plastic and reversible between monoclinous and pistillody depending on habitats, the offspring maintained the maternal genders in the first year but changed from year 2 to 5, and there was a cubic relationship between the rate of population gender changes and environmental variations. This relationship indicates that the species must overcome a threshold of environmental variations to switch its developmental path ways between the two genders. This threshold and the maternal gender stability cause a significant delay of gender changes in new environments. At the same time, they result in and maintain the two distinct habitat dependent gender phenotypes. We also observed that there was a significant and adaptive life-history differentiation between monoclinous and pistillody individuals and the gender phenotypes were developmentally linked with the life-history traits. Therefore, the gender phenotypes are adaptive. Low seed production, seed germination failure and matching phenotypes to habitats by gender plasticity indicate that the adaptive phenotypic diversity in A. philoxeroides may not be the result of ecological selection, but of gender plasticity. The delay of the adaptive gender phenotype realization in changing environments can maintain the differentiation between gender systems and their associated life-history traits, which may be an important component in evolution of novel traits and

  15. Phenotypic differentiation is associated with gender plasticity and its responsive delay to environmental changes in Alternanthera philoxeroides--phenotypic differentiation in alligator weed.

    Directory of Open Access Journals (Sweden)

    Wei Liu

    Full Text Available Phenotypic plasticity is common in many taxa, and it may increase an organism's fitness in heterogeneous environments. However, in some cases, the frequency of environmental changes can be faster than the ability of the individual to produce new adaptive phenotypes. The importance of such a time delay in terms of individual fitness and species adaptability has not been well studied. Here, we studied gender plasticity of Alternanthera philoxeroides to address this issue through a reciprocal transplant experiment. We observed that the genders of A. philoxeroides were plastic and reversible between monoclinous and pistillody depending on habitats, the offspring maintained the maternal genders in the first year but changed from year 2 to 5, and there was a cubic relationship between the rate of population gender changes and environmental variations. This relationship indicates that the species must overcome a threshold of environmental variations to switch its developmental path ways between the two genders. This threshold and the maternal gender stability cause a significant delay of gender changes in new environments. At the same time, they result in and maintain the two distinct habitat dependent gender phenotypes. We also observed that there was a significant and adaptive life-history differentiation between monoclinous and pistillody individuals and the gender phenotypes were developmentally linked with the life-history traits. Therefore, the gender phenotypes are adaptive. Low seed production, seed germination failure and matching phenotypes to habitats by gender plasticity indicate that the adaptive phenotypic diversity in A. philoxeroides may not be the result of ecological selection, but of gender plasticity. The delay of the adaptive gender phenotype realization in changing environments can maintain the differentiation between gender systems and their associated life-history traits, which may be an important component in evolution of novel

  16. Protective effect of ischemic preconditioning on liver

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To study the protective effect of ischemicpreconditioning (IPC) on the hepatic ischemia-reperfusion injury.Methods: The model of rat liver subjected to ischemia/reperfusion (I/R) injury was made. All 24 mice were divided randomly into 3 groups and anesthetized by 2% sodium pentobarbital (30-40 mg/kg). The enzyme activity of AST, ALT, LDH, SOD and the content of LPO were assayed respectively. Specimens were observed under transmission electron microscope.Results: IPC prevented the increase of ALT, AST and LDH in the blood and that of LPO in the tissues (P<0.05), and maintained high level of SOD in the tissues (P<0.05).Conclusions: IPC has protective effect on the liver function.

  17. Maintaining heterokaryosis in pseudo-homothallic fungi.

    Science.gov (United States)

    Grognet, Pierre; Silar, Philippe

    2015-01-01

    Among all the strategies displayed by fungi to reproduce and propagate, some species have adopted a peculiar behavior called pseudo-homothallism. Pseudo-homothallic fungi are true heterothallics, i.e., they need 2 genetically-compatible partners to mate, but they produce self-fertile mycelium in which the 2 different nuclei carrying the compatible mating types are present. This lifestyle not only enables the fungus to reproduce without finding a compatible partner, but also to cross with any mate it may encounter. However, to be fully functional, pseudo-homothallism requires maintaining heterokaryosis at every stage of the life cycle. We recently showed that neither the structure of the mating-type locus nor hybrid-enhancing effect due to the presence of the 2 mating types accounts for the maintenance of heterokaryosis in the pseudo-homothallic fungus P. anserina. In this addendum, we summarize the mechanisms creating heterokaryosis in P. anserina and 2 other well-known pseudo-homothallic fungi, Neurospora tetrasperma and Agaricus bisporus. We also discuss mechanisms potentially involved in maintaining heterokaryosis in these 3 species.

  18. Maintaining extensivity in evolutionary multiplex networks

    CERN Document Server

    Antonopoulos, Chris G

    2015-01-01

    In this Letter, we explore the role of network topology on its extensive character. We study analytically and numerically how the topology contributes to maintaining extensivity of entropy in multiplex networks, i.e. networks of subnetworks, by means of the sum of the positive Lyapunov exponents, $H_{KS}$, a quantity related to entropy. We show that extensivity relies not only on the interplay between the coupling strengths of the dynamics associated to the intra (short-range) and inter (long-range) interactions, but also on the sum of the intra-degrees of the nodes of the subnetworks. For the analytically treated networks of size $N$, if the sum of the intra-degrees (and the sum of inter-degrees) scales as $N^{\\theta+1}$, extensivity can be maintained if the intra-coupling (and the inter-coupling) strength scales as $N^{-\\theta}$, when evolution is driven by the maximization of $H_{KS}$. We then verify our analytical result by doing numerical simulations in multiplex networks formed by electrically and chemi...

  19. Experience of maintaining laboratory educational website's sustainability

    Science.gov (United States)

    Dimenstein, Izak B.

    2016-01-01

    Laboratory methodology websites are specialized niche websites. The visibility of a niche website transforms it into an authority site on a particular “niche of knowledge.” This article presents some ways in which a laboratory methodology website can maintain its sustainability. The optimal composition of the website includes a basic content, a blog, and an ancillary part. This article discusses experimenting with the search engine optimization query results page. Strategic placement of keywords and even phrases, as well as fragmentation of the post's material, can improve the website's visibility to search engines. Hyperlinks open a chain reaction of additional links and draw attention to the previous posts. Publications in printed periodicals are a substantial part of a niche website presence on the Internet. Although this article explores a laboratory website on the basis of our hands-on expertise maintaining “Grossing Technology in Surgical Pathology” (www.grossing-technology.com) website with a high volume of traffic for more than a decade, the recommendations presented here for developing an authority website can be applied to other professional specialized websites. The authority websites visibility and sustainability are preconditions for aggregating them in a specialized educational laboratory portal. PMID:27688928

  20. Experience of maintaining laboratory educational website's sustainability.

    Science.gov (United States)

    Dimenstein, Izak B

    2016-01-01

    Laboratory methodology websites are specialized niche websites. The visibility of a niche website transforms it into an authority site on a particular "niche of knowledge." This article presents some ways in which a laboratory methodology website can maintain its sustainability. The optimal composition of the website includes a basic content, a blog, and an ancillary part. This article discusses experimenting with the search engine optimization query results page. Strategic placement of keywords and even phrases, as well as fragmentation of the post's material, can improve the website's visibility to search engines. Hyperlinks open a chain reaction of additional links and draw attention to the previous posts. Publications in printed periodicals are a substantial part of a niche website presence on the Internet. Although this article explores a laboratory website on the basis of our hands-on expertise maintaining "Grossing Technology in Surgical Pathology" (www.grossing-technology.com) website with a high volume of traffic for more than a decade, the recommendations presented here for developing an authority website can be applied to other professional specialized websites. The authority websites visibility and sustainability are preconditions for aggregating them in a specialized educational laboratory portal.

  1. Hepato-biliary profile of potential candidate liver progenitor cells from healthy rat liver

    Institute of Scientific and Technical Information of China (English)

    Céric Maerckx; Isabelle Scheers; Tatiana Tondreau; David Campard; Omar Nyabi; Mustapha Najimi; Etienne Sokal

    2012-01-01

    AIM:To evaluate the presence of progenitor cells in healthy adult rat liver displaying the equivalent advanced hepatogenic profile as that obtained in humans.METHODS:Rat fibroblastic-like liver derived cells (rFLDC) were obtained from collagenase-isolated liver cell suspensions and characterized and their phenotype profile determined using flow cytometry,immunocyto-chemistry,reverse transcription polymerase chain reaction and functional assays.RESULTS:rFLDC exhibit fibroblastoid morphology,express mesenchymal (CD73,CD90,vimentin,α-smooth muscle actin),hepatocyte (UGT1A1,CK8) and biliary (CK19) markers.Moreover,these cells are able to store glycogen,and have glucose 6 phosphatase activity,but not UGT1A1 activity.Under the hepatogenic differentiation protocol,rFLDC display an up-regulation of hepatocyte markers expression (albumin,tryptophan 2,3-dioxygenase,G6Pase) correlated to a down-regulation of the expression of the biliary marker CK19.CONCLUSION:Advanced hepatic features observed in human liver progenitor cells could not be demonstrated in rFLDC.However,we demonstrated the presence of an original rodent hepato-biliary cell type.

  2. Excellent survival after liver transplantation for isolated polycystic liver disease : an European Liver Transplant Registry study

    NARCIS (Netherlands)

    van Keimpema, Loes; Nevens, Frederik; Adam, Rene; Porte, Robert J.; Fikatas, Panagiotis; Becker, Thomas; Kirkegaard, Preben; Metselaar, Herold J.; Drenth, Joost P. H.

    2011-01-01

    Patients with end-stage isolated polycystic liver disease (PCLD) suffer from incapacitating symptoms because of very large liver volumes. Liver transplantation (LT) is the only curative option. This study assesses the feasibility of LT in PCLD. We used the European Liver Transplant Registry (ELTR) d

  3. Excellent survival after liver transplantation for isolated polycystic liver disease: an European Liver Transplant Registry study

    DEFF Research Database (Denmark)

    van Keimpema, Loes; Nevens, Frederik; Adam, René

    2011-01-01

    Patients with end-stage isolated polycystic liver disease (PCLD) suffer from incapacitating symptoms because of very large liver volumes. Liver transplantation (LT) is the only curative option. This study assesses the feasibility of LT in PCLD. We used the European Liver Transplant Registry (ELTR...

  4. Excellent survival after liver transplantation for isolated polycystic liver disease : an European Liver Transplant Registry study

    NARCIS (Netherlands)

    van Keimpema, Loes; Nevens, Frederik; Adam, Rene; Porte, Robert J.; Fikatas, Panagiotis; Becker, Thomas; Kirkegaard, Preben; Metselaar, Herold J.; Drenth, Joost P. H.

    2011-01-01

    Patients with end-stage isolated polycystic liver disease (PCLD) suffer from incapacitating symptoms because of very large liver volumes. Liver transplantation (LT) is the only curative option. This study assesses the feasibility of LT in PCLD. We used the European Liver Transplant Registry (ELTR)

  5. HYPERVASCULAR LIVER LESIONS IN RADIOLOGICALLY NORMAL LIVER.

    Science.gov (United States)

    Amico, Enio Campos; Alves, José Roberto; Souza, Dyego Leandro Bezerra de; Salviano, Fellipe Alexandre Macena; João, Samir Assi; Liguori, Adriano de Araújo Lima

    2017-01-01

    The hypervascular liver lesions represent a diagnostic challenge. To identify risk factors for cancer in patients with non-hemangiomatous hypervascular hepatic lesions in radiologically normal liver. This prospective study included patients with hypervascular liver lesions in radiologically normal liver. The diagnosis was made by biopsy or was presumed on the basis of radiologic stability in follow-up period of one year. Cirrhosis or patients with typical imaging characteristics of haemangioma were excluded. Eighty-eight patients were included. The average age was 42.4. The lesions were unique and were between 2-5 cm in size in most cases. Liver biopsy was performed in approximately 1/3 of cases. The lesions were benign or most likely benign in 81.8%, while cancer was diagnosed in 12.5% of cases. Univariate analysis showed that age >45 years (p3 nodules (p=0.003) and elevated alkaline phosphatase (p=0.013) were significant risk factors for cancer. It is safe to observe hypervascular liver lesions in normal liver in patients up to 45 years, normal alanine aminotransaminase, up to three nodules and no personal history of cancer. Lesion biopsies are safe in patients with atypical lesions and define the treatment to be established for most of these patients. As lesões hepáticas hipervasculares representam um desafio diagnóstico. Identificar fatores de risco para câncer em pacientes portadores de lesão hepática hipervascular não-hemangiomatosa em fígado radiologicamente normal. Estudo prospectivo que incluiu pacientes com lesões hepáticas hipervasculares em que o diagnóstico final foi obtido por exame anatomopatológico ou, presumido a partir de seguimento mínimo de um ano. Diagnóstico prévio de cirrose ou radiológico de hemangioma foram considerados critérios de exclusão. Oitenta e oito pacientes foram incluídos. A relação mulher/homem foi de 5,3/1. A idade média foi de 42,4 anos. Na maior parte das vezes as lesões hepáticas foram únicas e com

  6. Phenotypic screens targeting neurodegenerative diseases.

    Science.gov (United States)

    Zhang, Minhua; Luo, Guangrui; Zhou, Yanjiao; Wang, Shaohui; Zhong, Zhong

    2014-01-01

    Neurodegenerative diseases affect millions of people worldwide, and the incidences increase as the population ages. Disease-modifying therapy that prevents or slows disease progression is still lacking, making neurodegenerative diseases an area of high unmet medical need. Target-based drug discovery for disease-modifying agents has been ongoing for many years, without much success due to incomplete understanding of the molecular mechanisms underlying neurodegeneration. Phenotypic screening, starting with a disease-relevant phenotype to screen for compounds that change the outcome of biological pathways rather than activities at certain specific targets, offers an alternative approach to find small molecules or targets that modulate the key characteristics of neurodegeneration. Phenotypic screens that focus on amelioration of disease-specific toxins, protection of neurons from degeneration, or promotion of neuroregeneration could be potential fertile grounds for discovering therapeutic agents for neurodegenerative diseases. In this review, we will summarize the progress of compound screening using these phenotypic-based strategies for this area, with a highlight on unique considerations for disease models, assays, and screening methodologies. We will further provide our perspectives on how best to use phenotypic screening to develop drug leads for neurodegenerative diseases.

  7. Chromosomal phenotypes and submicroscopic abnormalities

    Directory of Open Access Journals (Sweden)

    Devriendt Koen

    2004-01-01

    Full Text Available Abstract The finding, during the last decade, that several common, clinically delineated syndromes are caused by submicroscopic deletions or, more rarely, by duplications, has provided a powerful tool in the annotation of the human genome. Since most microdeletion/microduplication syndromes are defined by a common deleted/duplicated region, abnormal dosage of genes located within these regions can explain the phenotypic similarities among individuals with a specific syndrome. As such, they provide a unique resource towards the genetic dissection of complex phenotypes such as congenital heart defects, mental and growth retardation and abnormal behaviour. In addition, the study of phenotypic differences in individuals with the same microdeletion syndrome may also become a treasury for the identification of modifying factors for complex phenotypes. The molecular analysis of these chromosomal anomalies has led to a growing understanding of their mechanisms of origin. Novel tools to uncover additional submicroscopic chromosomal anomalies at a higher resolution and higher speed, as well as the novel tools at hand for deciphering the modifying factors and epistatic interactors, are 'on the doorstep' and will, besides their obvious diagnostic role, play a pivotal role in the genetic dissection of complex phenotypes.

  8. Metabolism, Genomics, and DNA Repair in the Mouse Aging Liver

    Directory of Open Access Journals (Sweden)

    Michel Lebel

    2011-01-01

    Full Text Available The liver plays a pivotal role in the metabolism of nutrients, drugs, hormones, and metabolic waste products, thereby maintaining body homeostasis. The liver undergoes substantial changes in structure and function within old age. Such changes are associated with significant impairment of many hepatic metabolic and detoxification activities, with implications for systemic aging and age-related disease. It has become clear, using rodent models as biological tools, that genetic instability in the form of gross DNA rearrangements or point mutations accumulate in the liver with age. DNA lesions, such as oxidized bases or persistent breaks, increase with age and correlate well with the presence of senescent hepatocytes. The level of DNA damage and/or mutation can be affected by changes in carcinogen activation, decreased ability to repair DNA, or a combination of these factors. This paper covers some of the DNA repair pathways affecting liver homeostasis with age using rodents as model systems.

  9. Caring for the woman with acute fatty liver of pregnancy.

    Science.gov (United States)

    Holub, Karen; Camune, Barbara

    2015-01-01

    Acute fatty liver of pregnancy, although rare, is usually a third trimester of pregnancy occurrence that may be life threatening for both the pregnant woman and the fetus. Often, the onset resembles gastroenteritis or cholecystitis and correct diagnosis is delayed. Because it can also present with preeclampsia and eclampsia, it may be mistakenly diagnosed as hemolysis, elevated liver enzymes, low platelet syndrome. This article presents diagnostic differences between liver conditions that can complicate pregnancy and management strategies for treating and maintaining the well-being of pregnant women, fetuses, and infants who are affected by acute fatty liver of pregnancy. Early recognition and rapid intervention from antepartum diagnosis through delivery and the postpartum period are required by the nursing team and medical providers to reduce maternal and neonatal morbidity and mortality.

  10. Alloimmunization in multitransfused liver disease patients: Impact of underlying disease

    Directory of Open Access Journals (Sweden)

    Meenu Bajpai

    2016-01-01

    Full Text Available Introduction: Transfusion support is vital to the management of patients with liver diseases. Repeated transfusions are associated with many risks such as transfusion-transmitted infection, transfusion immunomodulation, and alloimmunization. Materials and Methods: A retrospective data analysis of antibody screening and identification was done from February 2012 to February 2014 to determine the frequency and specificity of irregular red-cell antibodies in multitransfused liver disease patients. The clinical and transfusion records were reviewed. The data was compiled, statistically analyzed, and reviewed. Results: A total of 842 patients were included in our study. Alloantibodies were detected in 5.22% of the patients. Higher rates of alloimmunization were seen in patients with autoimmune hepatitis, cryptogenic liver disease, liver damage due to drugs/toxins, and liver cancer patients. Patients with alcoholic liver disease had a lower rate of alloimmunization. The alloimmunization was 12.7% (23/181 in females and 3.17% (21/661 in males. Antibodies against the Rh system were the most frequent with 27 of 44 alloantibodies (61.36%. The most common alloantibody identified was anti-E (11/44 cases, 25%, followed by anti-C (6/44 cases, 13.63%. Conclusion: Our findings suggest that alloimmunization rate is affected by underlying disease. Provision of Rh and Kell phenotype-matched blood can significantly reduce alloimmunization.

  11. Chronic Glucocorticoid-Rich Milieu and Liver Dysfunction

    Directory of Open Access Journals (Sweden)

    Hernán Gonzalo Villagarcía

    2016-01-01

    Full Text Available We investigated the impact of chronic hypercorticosteronemia (due to neonatal monosodium L-glutamate, MSG, and treatment on liver oxidative stress (OS, inflammation, and carbohydrate/lipid metabolism in adult male rats. We evaluated the peripheral concentrations of several metabolic and OS markers and insulin resistance indexes. In liver we assessed (a OS (GSH and protein carbonyl groups and inflammatory (IL-1b, TNFa, and PAI-1 biomarkers and (b carbohydrate and lipid metabolisms. MSG rats displayed degenerated optic nerves, hypophagia, low body and liver weights, and enlarged adipose tissue mass; higher peripheral levels of glucose, triglycerides, insulin, uric acid, leptin, corticosterone, transaminases and TBARS, and peripheral and liver insulin resistance; elevated liver OS, inflammation markers, and glucokinase (mRNA/activity and fructokinase (mRNA. Additionally, MSG liver phosphofructokinase-2, glucose-6-phosphatase (mRNA and activity and glucose-6-phosphate dehydrogenase, Chrebp, Srebp1c, fatty acid synthase, and glycerol-3-phosphate (mRNAs were increased. In conclusion adult MSG rats developed an insulin-resistant state and increased OS and serious hepatic dysfunction characterized by inflammation and metabolic signs suggesting increased lipogenesis. These features, shared by both metabolic and Cushing’s syndrome human phenotypes, support that a chronic glucocorticoid-rich endogenous environment mainly impacts on hepatic glucose cycle, displacing local metabolism to lipogenesis. Whether correcting the glucocorticoid-rich environment ameliorates such dysfunctions requires further investigation.

  12. Maintaining immunological tolerance with Foxp3

    Institute of Scientific and Technical Information of China (English)

    Lauren E Mays; Youhai H Chen

    2007-01-01

    Central tolerance in the thymus is the primary mechanism for deleting autoreactive T cells.Despite this,escape of self-reactive T lymphocytes into the periphery reveals the threat of autoimmunity.To compensate for its imperfection,the thymus also produces a naturally occurring subset ofFoxp3+CD4+CD25+regulatory T cells with suppressive function,capable of controlling autoreactive cells.Foxp3(forkhead box P3),the lineage-specific marker for this subset of cells,is crucial to their thymic development and peripheral function,and yet the transcriptional program driven by Foxp3 was until now largely undefined.Emerging evidence has provided insight into its role:from the ability of Foxp3 to cooperate with other transcription factors such as NFAT,to the genome-wide characterization of target genes directly bound and regulated by Foxp3.Here we discuss the discovery of naturally occurring regulatory T cells-their phenotype,development,maintenance,and function-largely as they are defined by the lineage-specific marker,Foxp3.

  13. [A Case of Sigmoid Colon Cancer with Synchronous Liver Metastasis, Treated with Laparoscopic Liver Resection after SOX plus BV Chemotherapy].

    Science.gov (United States)

    Shimizu, Yasuhito; Ando, Katsuhiko; Oda, Kenji; Kubosawa, Hitoshi; Miyazaki, Masaru

    2015-11-01

    We performed laparoscopic liver resection in a patient with synchronous liver metastasis from advanced sigmoid colon cancer after induction with S-1 plus oxaliplatin (SOX) plus bevacizumab (BV) chemotherapy. A 61-year-old woman underwent laparoscopy-assisted sigmoidectomy for locally advanced sigmoid colon cancer with synchronous liver metastasis. SOX plus BV chemotherapy was initiated. After 3 courses, the liver tumor was downsized, and metastasectomy was performed laparoscopically with R0 resection. The postoperative course was uneventful and the patient was discharged on the 11th postoperative day. She has been free from recurrence. Induction with SOX plus BV chemotherapy is considered to be not only effective, but also beneficial for maintaining the quality of life (QOL) in patients with advanced colorectal cancer.

  14. The Involvement of Heat Shock Proteins in Murine Liver Regeneration

    Institute of Scientific and Technical Information of China (English)

    Qing Shi; Zhongjun Dong; Haiming Wei

    2007-01-01

    Partial hepatectomy (PHx) in mammals is a very common experimental model to investigate the process of liver regeneration. The surgery itself could give birth to a series of stresses, such as the temporary raise of body temperature and the ischaemia-reperfusion injury. Heat shock proteins (HSPs) were a family of stress-inducible proteins involved in maintaining cell homeostasis and regulating the immune system. In our study, we intended to investigate the expression and role of HSPs in liver regeneration. Using RT-PCR and Western blotting, we determined the expression in regenerating liver of HSP27, HSP60, HSP70 and HSP90 in mRNA level and protein level, respectively, with mice treated with sham operation as controls. We also used quercertin as an inhibitior of HSPs to explore their effects on liver regeneration. We found that hepatic expression of HSPs increased at the early phase of liver regeneration and declined to the constitutively low level later. Moreover, quercetin pretreatment delayed the progress of liver regeneration in mice via inhibition of HSPs. The results indicated that HSPs played an important role in liver regeneration.

  15. Liver transplantation for polycystic liver and massive hepatomegaly

    Institute of Scientific and Technical Information of China (English)

    Salvatore; Gruttadauria; Fabrizio; di; Francesco; Bruno; Gridelli

    2010-01-01

    Liver tumor and other benign liver diseases such as polycystic liver disease can cause massive hepatomegaly and may represent an indication for liver transplantation(LT)in some instances.In this setting,LT can be extremely difficult and challenging due to its decreased mobility and access to vascular supply.Benefit from either a right or a left partial liver resection during the transplant procedure has been advocated to safely accomplish the hepatectomy of the native liver.Although we believe that partial ...

  16. Maintaining the Telescope Bibliography at Gemini Observatory

    Science.gov (United States)

    Zhang, X.

    2010-10-01

    The library profession benefits tremendously from ever-changing web technologies. In maintaining a telescope bibliography, web-publishing revolutionized the way librarians track relevant publications. Thanks to the search abilities provided by the NASA Astrophysics Data System, arXiv, publishers, as well as Google Scholar, and other such resources, online searching for Gemini-based publications has replaced the tedious perusing of print journals. However, we should keep in mind that online searching is neither flawless nor simple — different content providers require different search strategies. Sometimes the retrievals are not as complete as one expects. Information providers should be constantly improving their searching abilities in order to make the task of electronic publication tracking more reliable and efficient.

  17. [Maintaining solidarity: is mutuality the solution?].

    Science.gov (United States)

    Gevers, J K M; Ploem, M C

    2013-01-01

    Solidarity is essentially the willingness to contribute to the community and its demands, which may even involve contributing more than one is expecting to receive. Another principle is mutuality: this refers to a balance between rights and obligations or between mutual obligations. In its advisory document 'The importance of mutuality......solidarity takes work!', The Dutch Council for Public Health and Health Care underlines the importance of ensuring solidarity within the Dutch health care system, e.g. by encouraging patients to take responsibility for their own health, possibly by introducing elements of mutuality. In our contribution, we comment on the Council's advice. Although we fully agree with the overall conclusion that solidarity should be maintained within the system, we do not see how the introduction of increased mutuality will contribute to this goal.

  18. Maintaining and troubleshooting your 3D printer

    CERN Document Server

    Bell, Charles

    2014-01-01

    Maintaining and Troubleshooting Your 3D Printer by Charles Bell is your guide to keeping your 3D printer running through preventive maintenance, repair, and diagnosing and solving problems in 3D printing. If you've bought or built a 3D printer such as a MakerBot only to be confounded by jagged edges, corner lift, top layers that aren't solid, or any of a myriad of other problems that plague 3D printer enthusiasts, then here is the book to help you get past all that and recapture the joy of creative fabrication. The book also includes valuable tips for builders and those who want to modify the

  19. Motives for maintaining personal journal blogs.

    Science.gov (United States)

    Hollenbaugh, Erin E

    2011-01-01

    Although much has been learned about political and news blogs, there has been a lack of research on personal journal blogs. They deserve further research attention because of the implications blogs have in many bloggers' immediate social networks, as well as the opportunities for scientific inquiry in a rich and evolving communication environment. This study explored bloggers' motives for maintaining personal journal blogs, or blogs that resemble diaries about one's personal life. Stemming from the uses and gratifications perspective, antecedents (age, sex, loneliness, disclosiveness) and blogging motives composed a model for predicting the amount of blog use. Seven motives emerged from online survey data: helping/informing, social connection, pass time, exhibitionism, archiving/organizing, professionalism, and get feedback. Age, sex, loneliness, and disclosiveness predicted different motives, and the total model (age, sex, loneliness, disclosiveness, and motives) was useful for explaining 13% of the variance in the amount of blog use.

  20. Heartwarming memories: Nostalgia maintains physiological comfort.

    Science.gov (United States)

    Zhou, Xinyue; Wildschut, Tim; Sedikides, Constantine; Chen, Xiaoxi; Vingerhoets, Ad J J M

    2012-08-01

    Nostalgia, a sentimental longing or wistful affection for the past, is a predominantly positive and social emotion. Recent evidence suggests that nostalgia maintains psychological comfort. Here, we propose, and document in five methodologically diverse studies, a broader homeostatic function for nostalgia that also encompasses the maintenance of physiological comfort. We show that nostalgia--an emotion with a strong connotation of warmth--is triggered by coldness. Participants reported stronger nostalgia on colder (vs. warmer) days and in a cold (vs. neutral or warm) room. Nostalgia, in turn, modulates the interoceptive feeling of temperature. Higher levels of music-evoked nostalgia predicted increased physical warmth, and participants who recalled a nostalgic (vs. ordinary autobiographical) event perceived ambient temperature as higher. Finally, and consistent with the close central nervous system integration of temperature and pain sensations, participants who recalled a nostalgic (vs. ordinary autobiographical) event evinced greater tolerance to noxious cold.

  1. How homologous recombination maintains telomere integrity.

    Science.gov (United States)

    Tacconi, Eliana M C; Tarsounas, Madalena

    2015-06-01

    Telomeres protect the ends of linear chromosomes against loss of genetic information and inappropriate processing as damaged DNA and are therefore crucial to the maintenance of chromosome integrity. In addition to providing a pathway for genome-wide DNA repair, homologous recombination (HR) plays a key role in telomere replication and capping. Consistent with this, the genomic instability characteristic of HR-deficient cells and tumours is driven in part by telomere dysfunction. Here, we discuss the mechanisms by which HR modulates the response to intrinsic cellular challenges that arise during telomere replication, as well as its impact on the assembly of telomere protective structures. How normal and tumour cells differ in their ability to maintain telomeres is deeply relevant to the search for treatments that would selectively eliminate cells whose capacity for HR-mediated repair has been compromised.

  2. Sox17 regulates liver lipid metabolism and adaptation to fasting.

    Science.gov (United States)

    Rommelaere, Samuel; Millet, Virginie; Vu Manh, Thien-Phong; Gensollen, Thomas; Andreoletti, Pierre; Cherkaoui-Malki, Mustapha; Bourges, Christophe; Escalière, Bertrand; Du, Xin; Xia, Yu; Imbert, Jean; Beutler, Bruce; Kanai, Yoshiakira; Malissen, Bernard; Malissen, Marie; Tailleux, Anne; Staels, Bart; Galland, Franck; Naquet, Philippe

    2014-01-01

    Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is depressed. This mouse carries a mutation in the HMG domain of the Sox17 transcription factor. Mutant mice display a metabolic phenotype featuring lipid abnormalities and inefficient adaptation to fasting. Upon fasting, a fraction of the PPARα-driven transcriptional program is no longer induced and associated with impaired fatty acid oxidation. The transcriptional phenotype is partially observed in heterozygous Sox17+/- mice. In mutant mice, the fasting phenotype but not all transcriptomic signature is rescued by the administration of the PPARalpha agonist fenofibrate. These results identify a novel role for Sox17 in adult liver as a modulator of the metabolic adaptation to fasting.

  3. Sox17 regulates liver lipid metabolism and adaptation to fasting.

    Directory of Open Access Journals (Sweden)

    Samuel Rommelaere

    Full Text Available Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is depressed. This mouse carries a mutation in the HMG domain of the Sox17 transcription factor. Mutant mice display a metabolic phenotype featuring lipid abnormalities and inefficient adaptation to fasting. Upon fasting, a fraction of the PPARα-driven transcriptional program is no longer induced and associated with impaired fatty acid oxidation. The transcriptional phenotype is partially observed in heterozygous Sox17+/- mice. In mutant mice, the fasting phenotype but not all transcriptomic signature is rescued by the administration of the PPARalpha agonist fenofibrate. These results identify a novel role for Sox17 in adult liver as a modulator of the metabolic adaptation to fasting.

  4. Expression QTL modules as functional components underlying higher-order phenotypes.

    Directory of Open Access Journals (Sweden)

    Lei Bao

    Full Text Available Systems genetics studies often involve the mapping of numerous regulatory relations between genetic loci and expression traits. These regulatory relations form a bipartite network consisting of genetic loci and expression phenotypes. Modular network organizations may arise from the pleiotropic and polygenic regulation of gene expression. Here we analyzed the expression QTL (eQTL networks derived from expression genetic data of yeast and mouse liver and found 65 and 98 modules respectively. Computer simulation result showed that such modules rarely occurred in randomized networks with the same number of nodes and edges and same degree distribution. We also found significant within-module functional coherence. The analysis of genetic overlaps and the evidences from biomedical literature have linked some eQTL modules to physiological phenotypes. Functional coherence within the eQTL modules and genetic overlaps between the modules and physiological phenotypes suggests that eQTL modules may act as functional units underlying the higher-order phenotypes.

  5. Polk Mutant Mice Have a Spontaneous Mutator Phenotype

    Science.gov (United States)

    Stancel, J. Nicole Kosarek; McDaniel, Lisa D.; Velasco, Susana; Richardson, James; Guo, Caixia; Friedberg, Errol C.

    2009-01-01

    Mice defective in the Polk gene (which encodes DNA polymerase kappa) are viable and do not manifest obvious phenotypes. The present studies document a spontaneous mutator phenotype in Polk−/− mice. The initial indication of enhanced spontaneous mutations in these mice came from the serendipitous observation of a postulated founder mutation that manifested in multiple disease states among a cohort of mice comprising all three possible Polk genotypes. Polk−/− and isogenic wild type controls carrying a reporter transgene (the λ-phage cII gene) were used for subsequent quantitative and qualitative studies on mutagenesis in various tissues. We observed significantly increased mutation frequencies in the kidney, liver, and lung of Polk−/− mice, but not in the spleen or testis. G:C base pairs dominated the mutation spectra of the kidney, liver, and lung. These results are consistent with the notion that Polκ is required for accurate translesion DNA synthesis past naturally occurring polycyclic guanine adducts, possibly generated by cholesterol and/or its metabolites. PMID:19783230

  6. Maintaining control is team's vital role.

    Science.gov (United States)

    Haywood, Liz; Frankel, Chris; Johns, Andrew

    2011-02-01

    In an environment where there is an ever-increasing use of reliable electronic control, it is easy to become complacent about the need for in-depth knowledge of how the controls actually work. After all, experts who can diagnose and fix such systems are only a phone call away, and a new unit can easily be fitted. Sometimes this is not the case at Bendigo Health, as we have a number of systems with a "black box" set of controls that can take days, or weeks, to fix, and cannot be fixed locally. To better manage and maintain our infrastructure, the Buildings & Infrastructure Department at Bendigo Health includes a number of employees who concentrate on building management systems (BMS). The BMS group plays a vital role in the complete lifecycle of projects that include control and monitoring of the plant within the hospital setting. A good example of this role was in the design, build, installation and commissioning, of two new negative pressure suites at Bendigo Health. The BMS group's involvement in this particular project included the door interlocking, the air conditioning and exhaust fan control, and a comprehensive alarm panel and overrides, all of which can be monitored centrally via the existing BMS system. The involvement of the BMS group, following the DHS guidelines, resulted in the architect and consulting engineers revisiting their designs and improving them to the benefit of both patient care and staff safety. The advantages of projects such as the negative pressure suites installed by the BMS group include the fact that that the hospital gains facilities that work correctly and according to industry guidelines; and the design, installation, and controls of the plant are understood by the people who will be maintaining the infrastructure. This paper will provide an overview of the work undertaken by the BMS group at Bendigo Health, using the negative pressure suites as an exemplar.

  7. Gut microbiota and liver diseases.

    Science.gov (United States)

    Minemura, Masami; Shimizu, Yukihiro

    2015-02-14

    Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases.

  8. Adenoviral overexpression of Lhx2 attenuates cell viability but does not preserve the stem cell like phenotype of hepatic stellate cells

    Energy Technology Data Exchange (ETDEWEB)

    Genz, Berit [Institute for Experimental Surgery, Rostock University Medical Center, Rostock (Germany); Thomas, Maria [Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart (Germany); Pützer, Brigitte M. [Institute of Experimental Gene Therapy and Cancer Research, Rostock University Medical Center, Rostock (Germany); Siatkowski, Marcin; Fuellen, Georg [Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock (Germany); Vollmar, Brigitte [Institute for Experimental Surgery, Rostock University Medical Center, Rostock (Germany); Abshagen, Kerstin, E-mail: kerstin.abshagen@uni-rostock.de [Institute for Experimental Surgery, Rostock University Medical Center, Rostock (Germany)

    2014-11-01

    Hepatic stellate cells (HSC) are well known initiators of hepatic fibrosis. After liver cell damage, HSC transdifferentiate into proliferative myofibroblasts, representing the major source of extracellular matrix in the fibrotic organ. Recent studies also demonstrate a role of HSC as progenitor or stem cell like cells in liver regeneration. Lhx2 is described as stem cell maintaining factor in different organs and as an inhibitory transcription factor in HSC activation. Here we examined whether a continuous expression of Lhx2 in HSC could attenuate their activation and whether Lhx2 could serve as a potential target for antifibrotic gene therapy. Therefore, we evaluated an adenoviral mediated overexpression of Lhx2 in primary HSC and investigated mRNA expression patterns by qRT-PCR as well as the activation status by different in vitro assays. HSC revealed a marked increase in activation markers like smooth muscle actin alpha (αSMA) and collagen 1α independent from adenoviral transduction. Lhx2 overexpression resulted in attenuated cell viability as shown by a slightly hampered migratory and contractile phenotype of HSC. Expression of stem cell factors or signaling components was also unaffected by Lhx2. Summarizing these results, we found no antifibrotic or stem cell maintaining effect of Lhx2 overexpression in primary HSC. - Highlights: • We performed adenoviral overexpression of Lhx2 in primary hepatic stellate cells. • Hepatic stellate cells expressed stem cell markers during cultivation. • Cell migration and contractility was slightly hampered upon Lhx2 overexpression. • Lhx2 overexpression did not affect stem cell character of hepatic stellate cells.

  9. ERManI is a target of miR-125b and promotes transformation phenotypes in hepatocellular carcinoma (HCC.

    Directory of Open Access Journals (Sweden)

    Shujuan Pan

    Full Text Available The MAN1B1 gene product, designated ER alpha-1, 2-mannosidase (ERManI, is an enzyme localized in the Golgi complex of mammalian cells. By functioning as a "gate keeper" to prevent the inappropriate secretion of misfolded glycoproteins, it plays a critical role in maintaining protein homeostasis in the mammalian secretory pathway. In the present study, we identified that a conserved motif within the 3'UTR of ERManI is a target of miR-125b, a microRNA frequently down-regulated in numerous types of cancers, including hepatocellular carcinoma (HCC. As predicted, the expression of ERManI is significantly elevated in HCC, as measured by immunohistochemistry in a liver spectrum tissue microarray. Additional analyses using several hepatoma cell lines demonstrated that the elevated ERManI inversely correlates with a diminished intracellular concentration of miR-125b. Moreover, functional studies indicated that RNAi-mediated knock-down of endogenous ERManI was sufficient to inhibit proliferation, migration, and invasion of hepatoma cells. These phenotypical changes occurred in the absence of alterations in global glycoprotein secretion or ER-stress status. Together, these results revealed a novel post-transcriptional regulatory mechanism for ERManI and implied that this molecule contributes to the regulation of carcinogenesis in HCC independent of its function in glycoprotein quality control.

  10. Cholangiocarcinoma: Correlation between Molecular Profiling and Imaging Phenotypes.

    Directory of Open Access Journals (Sweden)

    Eran Sadot

    Full Text Available To investigate associations between imaging features of cholangiocarcinoma by visual assessment and texture analysis, which quantifies heterogeneity in tumor enhancement patterns, with molecular profiles based on hypoxia markers.The institutional review board approved this HIPAA-compliant retrospective study of CT images of intrahepatic cholangiocarcinoma, obtained before surgery. Immunostaining for hypoxia markers (EGFR, VEGF, CD24, P53, MDM2, MRP-1, HIF-1α, CA-IX, and GLUT1 was performed on pre-treatment liver biopsies. Quantitative imaging phenotypes were determined by texture analysis with gray level co-occurrence matrixes. The correlations between quantitative imaging phenotypes, qualitative imaging features (measured by radiographic inspection alone, and expression levels of the hypoxia markers from the 25 tumors were assessed.Twenty-five patients were included with a median age of 62 years (range: 54-84. The median tumor size was 10.2 cm (range: 4-14, 10 (40% were single tumors, and 90% were moderately differentiated. Positive immunostaining was recorded for VEGF in 67% of the cases, EGFR in 75%, and CD24 in 55%. On multiple linear regression analysis, quantitative imaging phenotypes correlated significantly with EGFR and VEGF expression levels (R2 = 0.4, p<0.05 and R2 = 0.2, p<0.05, respectively, while a trend was demonstrated with CD24 expression (R2 = 0.33, p = 0.1. Three qualitative imaging features correlated with VEGF and CD24 expression (P<0.05, however, none of the qualitative features correlated with the quantitative imaging phenotypes.Quantitative imaging phenotypes, as defined by texture analysis, correlated with expression of specific markers of hypoxia, regardless of conventional imaging features.

  11. Leaf segmentation in plant phenotyping

    NARCIS (Netherlands)

    Scharr, Hanno; Minervini, Massimo; French, Andrew P.; Klukas, Christian; Kramer, David M.; Liu, Xiaoming; Luengo, Imanol; Pape, Jean Michel; Polder, Gerrit; Vukadinovic, Danijela; Yin, Xi; Tsaftaris, Sotirios A.

    2016-01-01

    Image-based plant phenotyping is a growing application area of computer vision in agriculture. A key task is the segmentation of all individual leaves in images. Here we focus on the most common rosette model plants, Arabidopsis and young tobacco. Although leaves do share appearance and shape cha

  12. Forensic DNA phenotyping : Regulatory issues

    NARCIS (Netherlands)

    Koops, E.J.; Schellekens, M.H.M.

    2008-01-01

    Forensic DNA phenotyping is an interesting new investigation method: crime-scene DNA is analyzed to compose a description of the unknown suspect, including external and behavioral features, geographic origin and perhaps surname. This method is allowed in some countries but prohibited in a few

  13. Forensic DNA phenotyping : Regulatory issues

    NARCIS (Netherlands)

    Koops, E.J.; Schellekens, M.H.M.

    2008-01-01

    Forensic DNA phenotyping is an interesting new investigation method: crime-scene DNA is analyzed to compose a description of the unknown suspect, including external and behavioral features, geographic origin and perhaps surname. This method is allowed in some countries but prohibited in a few others

  14. [Alcoholic liver disease and liver transplantation].

    Science.gov (United States)

    Testino, Gianni; Patussi, Valentino; Scafato, Emanuele

    2013-01-01

    Alcoholic liver disease (ALD) is the second most common diagnosis among patients undergoing liver transplantation (LT) in Europe and in the United States. The outcome of patients transplanted for ALD is at least as good as that for most other diagnoses and better than that for hepatitis C virus. In case of severe acute alcoholic hepatitis (AAH) non-responders to medical therapy, the reason for denying LT is that it requires abstinence from alcohol for six months before consideration for a transplant. A strict application of a period of abstinence as a policy for transplant eligibility is unfair to non-responder patients, as most of them will have died prior to the end of the six-month sober period. In our opinion, in severe AAH subjects with a good social support, with the frequency of self-help groups (alcoholics anonymous or association of clubs of alcoholics in treatment), with the frequency of Alcohol Unit and without severe psychotic or personality disorders, the lack of pre-LT abstinence alone should not be a barrier against being listed.

  15. Liver transplantation in Germany.

    Science.gov (United States)

    Tacke, Frank; Kroy, Daniela C; Barreiros, Ana Paula; Neumann, Ulf P

    2016-08-01

    Liver transplantation (LT) is a well-accepted procedure for end-stage liver disease in Germany. In 2015, 1489 patients were admitted to the waiting list (including 1308 new admissions), with the leading etiologies being fibrosis and cirrhosis (n = 349), alcoholic liver disease (n = 302), and hepatobiliary malignancies (n = 220). Organ allocation in Germany is regulated within the Eurotransplant system based on urgency as expressed by the Model for End-Stage Liver Disease score. In 2015, only 894 LTs (n = 48 from living donors) were performed at 23 German transplant centers, reflecting a shortage of organs. Several factors may contribute to the low number of organ donations. The German transplant legislation only accepts donation after brain death (not cardiac death), whereas advances in neurosurgery and a more frequently requested "palliative care" approach render fewer patients suitable as potential donors. The legislation further requires the active consent of the donor or first-degree relatives before donation. Ongoing debates within the German transplant field address the optimal management of patients with alcoholic liver cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma and measures to increase living donor transplantations. As a result of irregularities at mainly 4 German transplant centers that were exposed in 2012, guiding principles updated by the German authorities have since implemented strict rules (including internal and external auditing, the 8-eyes principle, mandatory repeated testing for alcohol consumption) to prohibit any manipulations in organ allocation. In conclusion, we will summarize important aspects on the management of LT in Germany, discuss legal and organizational aspects, and highlight challenges mainly related to the relative lack of organ donations, increasing numbers of extended criteria donors, and the peculiarities of the recipient patients. Liver Transplantation 22 1136-1142 2016 AASLD.

  16. Passage of bone-marrow-derived liver stem cells in a proliferating culture system

    Institute of Scientific and Technical Information of China (English)

    Yun-Feng Cai; Ji-Sheng Chen; Shu-Ying Su; Zuo-Jun Zhen; Huan-Wei Chen

    2009-01-01

    AIM: To explore the feasibility of passage of bonemarrow-derived liver stem cells (BDLSCs) in culture systems that contain cholestatic serum. METHODS: Whole bone marrow cells of rats were purified with conditioning selection media that contained 50 mL/L cholestatic serum. The selected BDLSCs were grown in a proliferating culture system and a differentiating culture system. The culture systems contained factors that stimulated the proliferation and differentiation of BDLSCs. Each passage of the proliferated stem cells was subjected to flow cytometry to detect stem cell markers. The morphology and phenotypic markers of BDLSCs were characterized using immunohistochemistry, reverse transcription polymerase chain reaction (RT-PCR) and electron microscopy. The metabolic functions of differentiated cells were also determined by glycogen staining and urea assay. RESULTS: The conditioning selection medium isolated BDLSCs directly from cultured bone marrow cells. The selected BDLSCs could be proliferated for six passages and maintained stable markers in our proliferating system. When the culture system was changed to a differentiating system, hepatocyte-like colony-forming units (H-CFUs) were formed. H-CFUs expressed markers of embryonic hepatocytes (alpha-fetoprotein, albumin and cytokeratin 8/18), biliary cells (cytokeratin 19), hepatocyte functional proteins (transthyretin and cytochrome P450-2b1), and hepatocyte nuclear factors 1α and -3β). They also had glycogen storage and urea synthesis functions, two of the critical features of hepatocytes. CONCLUSION: BDLSCs can be selected directly from bone marrow cells, and pure BDLSCs can be proliferated for six passages. The differentiated cells have hepatocyte-like phenotypes and functions. BDLSCs represent a new method to provide a readily available alternate source of cells for clinical hepatocyte therapy.

  17. Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy

    Institute of Scientific and Technical Information of China (English)

    Maria; Nicoline; Baandrup; Kristiansen; Sanne; Skovg?rd; Veidal; Kristoffer; Tobias; Gustav; Rigbolt; Kirstine; Sloth; T?lb?l; Jonathan; David; Roth; Jacob; Jelsing; Niels; Vrang; Michael; Feigh

    2016-01-01

    AIM:To characterize development of diet-induced nonalcoholic steatohepatitis(NASH)by performing live biopsy in wild-type and genetically obese mice.METHODS:Male wild-type C57BL/6J(C57)mice(DIO NASH)and male Lep ob/Lep ob(ob/ob)mice(ob/ob-NASH were maintained on a diet high in trans-fat(40%)fructose(22%)and cholesterol(2%)for 26 and 12 wk respectively.A normal chow diet served as control in C57 mice(lean chow)and ob/ob mice(ob/ob chow)After the diet-induction period,mice were liver biopsied and a blinded histological assessment of steatosis and fibrosis was conducted.Mice were then stratified into groups counterbalanced for steatosis score and fibrosi stage and continued on diet and to receive daily PO dosing of vehicle for 8 wk.Global gene expression in liver tissue was assessed by RNA sequencing and bioin formatics.Metabolic parameters,plasma liver enzyme and lipids(total cholesterol,triglycerides)as well a hepatic lipids and collagen content were measured b biochemical analysis.Non-alcoholic fatty liver disease activity score(NAS)(steatosis/inflammation/ballooningdegeneration)and fibrosis were scored.Steatosis and fibrosis were also quantified using percent fractional area.RESULTS:Diet-induction for 26 and 12 wk in DIONASH and ob/ob-NASH mice,respectively,elicited progressive metabolic perturbations characterized by increased adiposity,total cholesterol and elevated plasma liver enzymes.The diet also induced clear histological features of NASH including hepatosteatosis and fibrosis.Overall,the metabolic NASH phenotype was more pronounced in ob/ob-NASH vs DIO-NASH mice.During the eight week repeated vehicle dosing period,the metabolic phenotype was sustained in DIO-NASH and ob/ob-NASH mice in conjunction with hepatomegaly and increased hepatic lipids and collagen accumulation.Histopathological scoring demonstrated significantly increased NAS of DIO-NASH mice(0 vs4.7±0.4,P<0.001 compared to lean chow)and ob/ob-NASH mice(2.4±0.3 vs 6.3±0.2,P<0.001compared to ob

  18. Mental health services--maintaining strategic direction.

    Science.gov (United States)

    McFadyen, J A; Farrington, A

    1998-09-01

    AIM AND KEY ISSUES: This article reviews the theoretical basis of strategic management in an attempt to provide managers with a better understanding of the underpinning concepts and consequent actions they need to take to avoid loss of control and ultimate failure. The authors argue that community care for the severely mentally ill is failing and that in part the reason for this perceived failure is a closer allegiance to primary care that has shifted the focus away from mental illness. Such a shift, coupled with poor management and a desire by Community Mental Health Nurses (CMHNs) to retain a broad focus and maintain the 'autonomy' they gain when not held in the gravitational grasp of Consultant Psychiatrists, has resulted in strategic drift. The authors suggest 10 possible reasons to explain why CMHNs currently fail to meet the needs of the severely mentally ill. Among these are a lack of explicit strategic implementation plans, professional ambivalence and self-interest, poor management of resources and conflicting demands from key interest groups. It seems that mental health services in this country have reached the point where resistance to change should be crumbling in the face of perceived failure to deliver the required services. Whilst it could be argued that a major and potent source of internal change is performance gaps, few things force change more than sudden and unexpected information about poor organizational performance.

  19. Arteriolar niches maintain haematopoietic stem cell quiescence

    Science.gov (United States)

    Kunisaki, Yuya; Bruns, Ingmar; Scheiermann, Christoph; Ahmed, Jalal; Pinho, Sandra; Zhang, Dachuan; Mizoguchi, Toshihide; Wei, Qiaozhi; Lucas, Daniel; Ito, Keisuke; Mar, Jessica C.; Bergman, Aviv; Frenette, Paul S.

    2013-01-01

    Cell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSCs in the bone marrow (BM) remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging techniques and computational modelling to analyse significant tridimensional associations among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal BM. These arterioles are ensheathed exclusively by rare NG2+ pericytes, distinct from sinusoid-associated LepR+ cells. Pharmacological or genetic activation of HSC cell cycle alters the distribution of HSCs from NG2+ peri-arteriolar niches to LepR+ peri-sinusoidal niches. Conditional depletion of NG2+ cells induces HSC cycling and reduces functional long-term repopulating HSCs in BM. These results thus indicate that arteriolar niches are indispensable to maintain HSC quiescence. PMID:24107994

  20. MAVS maintains mitochondrial homeostasis via autophagy

    Science.gov (United States)

    Sun, Xiaofeng; Sun, Liwei; Zhao, Yuanyuan; Li, Ying; Lin, Wei; Chen, Dahua; Sun, Qinmiao

    2016-01-01

    Mitochondrial antiviral signalling protein (MAVS) acts as a critical adaptor protein to transduce antiviral signalling by physically interacting with activated RIG-I and MDA5 receptors. MAVS executes its functions at the outer membrane of mitochondria to regulate downstream antiviral signalling, indicating that the mitochondria provides a functional platform for innate antiviral signalling transduction. However, little is known about whether and how MAVS-mediated antiviral signalling contributes to mitochondrial homeostasis. Here we show that the activation of MAVS is sufficient to induce autophagic signalling, which may mediate the turnover of the damaged mitochondria. Importantly, we find MAVS directly interacts with LC3 through its LC3-binding motif ‘YxxI’, suggesting that MAVS might act as an autophagy receptor to mediate mitochondrial turnover upon excessive activation of RLR signalling. Furthermore, we provide evidence that both MAVS self-aggregation and its interaction with TRAF2/6 proteins are important for MAVS-mediated mitochondrial turnover. Collectively, our findings suggest that MAVS acts as a potential receptor for mitochondria-associated autophagic signalling to maintain mitochondrial homeostasis. PMID:27551434

  1. Arteriolar niches maintain haematopoietic stem cell quiescence.

    Science.gov (United States)

    Kunisaki, Yuya; Bruns, Ingmar; Scheiermann, Christoph; Ahmed, Jalal; Pinho, Sandra; Zhang, Dachuan; Mizoguchi, Toshihide; Wei, Qiaozhi; Lucas, Daniel; Ito, Keisuke; Mar, Jessica C; Bergman, Aviv; Frenette, Paul S

    2013-10-31

    Cell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSCs in the bone marrow remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging techniques and computational modelling to analyse significant three-dimensional associations in the mouse bone marrow among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal bone marrow. These arterioles are ensheathed exclusively by rare NG2 (also known as CSPG4)(+) pericytes, distinct from sinusoid-associated leptin receptor (LEPR)(+) cells. Pharmacological or genetic activation of the HSC cell cycle alters the distribution of HSCs from NG2(+) periarteriolar niches to LEPR(+) perisinusoidal niches. Conditional depletion of NG2(+) cells induces HSC cycling and reduces functional long-term repopulating HSCs in the bone marrow. These results thus indicate that arteriolar niches are indispensable for maintaining HSC quiescence.

  2. Sociable Robots through Self-maintained Energy

    Directory of Open Access Journals (Sweden)

    Henrik Schioler

    2008-11-01

    Full Text Available Research of autonomous mobile robots has mostly emphasized interaction and coordination that are natually inspired from biological behavior of birds, insects, and fish: flocking, foraging, collecting, and sharing. However, most research has been only focused on autonomous behaviors in order to perform robots like animals, whereas it is lacked of determinant to those behaviours: energy. Approaching to clusted amimal and the higher, collective and sharing food among individuals are major activity to keep society being. This paper issues an approach to sociable robots using self-maintained energy in cooperative mobile robots, which is dominantly inspired from swarm behavior of collecting and sharing food of honey-bee and ant. Autonomous mobile robots are usually equipped with a finite energy, thus they can operate in a finite time. To overcome the finitude, we describe practical deployment of mobile robots that are capable of carrying and exchanging fuel to other robots. Mechanism implementation including modular hardware and control architecture to demonstrate the capabicities of the approach is presented. Subsequently, the battery exchange algorithm basically based on probabilistic modeling of total energy on each robot located in its local vicinity is described. The paper is concluded with challenging works of chain of mobile robots, rescue, repair, and relation of heterogeneous robots.

  3. Sociable Robots Through Self-Maintained Energy

    Directory of Open Access Journals (Sweden)

    Trung Dung Ngo

    2006-12-01

    Full Text Available Research of autonomous mobile robots has mostly emphasized interaction and coordination that are natually inspired from biological behavior of birds, insects, and fish: flocking, foraging, collecting, and sharing. However, most research has been only focused on autonomous behaviors in order to perform robots like animals, whereas it is lacked of determinant to those behaviours: energy. Approaching to clusted amimal and the higher, collective and sharing food among individuals are major activity to keep society being. This paper issues an approach to sociable robots using self-maintained energy in cooperative mobile robots, which is dominantly inspired from swarm behavior of collecting and sharing food of honey-bee and ant. Autonomous mobile robots are usually equipped with a finite energy, thus they can operate in a finite time. To overcome the finitude, we describe practical deployment of mobile robots that are capable of carrying and exchanging fuel to other robots. Mechanism implementation including modular hardware and control architecture to demonstrate the capabicities of the approach is presented. Subsequently, the battery exchange algorithm basically based on probabilistic modeling of total energy on each robot located in its local vicinity is described. The paper is concluded with challenging works of chain of mobile robots, rescue, repair, and relation of heterogeneous robots.

  4. Superoxide dismutase phenotypes in duodenal ulcers: A genetic marker?

    Directory of Open Access Journals (Sweden)

    Sulekha S

    2006-01-01

    Full Text Available Background:Cu-Zn superoxide dismutases are antioxidative defensive enzymes that catalyze the reduction of superoxide anions to hydrogen peroxide. Aim:The study focuses on the association of electromorph of superoxide dismutase with duodenal ulcers, which result due to an imbalance between aggressive and defensive factors. Materials and Methods:Endoscopically confirmed 210 duodenal ulcer patients and 185 healthy individuals for comparative analysis were considered for the present study. Phenotyping of superoxide dismutase was carried out by subjecting the RBC membranes to polyacrylamide gel electrophoresis, using appropriate staining protocols. Results:Statistical analysis of SOD phenotypes revealed a significant increase of SOD AFNx012 allele and Superoxide dismutases (SOD 2-2 phenotype in duodenal ulcer group. Among these individuals, a predominance of Helicobacter pylori infection was observed. The increased preponderance of homozygotes can be explained on the basis of reduced and altered enzyme activity, which may lead to disturbance in homeostasis of antioxidant/oxidant culminating in high lipid peroxidative gastric mucosal tissue damage and ulceration. No variation in the distribution of SOD phenotypes with respect to Helicobacter pylori indicates the role of Mn-SOD rather than Cu-Zn SOD in the Helicobacter pylori infected cases as reported earlier. Conclusions:Superoxide dismutase as a genetic marker / gene modifier, encoding for an antioxidant enzyme in maintaining tissue homeostasis of the gastric mucosa is discussed.

  5. Distribution of phenotypically disparate myocyte subpopulations in airway smooth muscle.

    Science.gov (United States)

    Halayko, Andrew J; Stelmack, Gerald L; Yamasaki, Akira; McNeill, Karol; Unruh, Helmut; Rector, Edward

    2005-01-01

    Phenotype and functional heterogeneity of airway smooth muscle (ASM) cells in vitro is well known, but there is limited understanding of these features in vivo. We tested whether ASM is composed of myocyte subsets differing in contractile phenotype marker expression. We used flow cytometry to compare smooth muscle myosin heavy chain (smMHC) and smooth muscle-alpha-actin (sm-alpha-actin) abundance in myocytes dispersed from canine trachealis. Based on immunofluorescent intensity and light scatter characteristics (forward and 90 degrees side scatter), 2 subgroups were identified and isolated. Immunoblotting confirmed smMHC and sm-alpha-actin were 10- and 5-fold greater, respectively, in large, elongate myocytes that comprised approximately 60% of total cells. Immunohistochemistry revealed similar phenotype heterogeneity in human bronchial smooth muscle. Canine tracheal myocyte subpopulations isolated by flow cytometry were used to seed primary subcultures. Proliferation of subcultures established with myocytes exhibiting low levels of smMHC and sm-alpha-actin was approximately 2 x faster than subcultures established with ASM cells with a high marker protein content. These studies demonstrate broad phenotypic heterogeneity of myocytes in normal ASM tissue that is maintained in cell culture, as demonstrated by divergent proliferative capacity. The distinct roles of these subgroups could be a key determinant of normal and pathological lung development and biology.

  6. Mouse embryonic fibroblasts derived from Odin deficient mice display a hyperproliiferative phenotype

    DEFF Research Database (Denmark)

    Kristiansen, Troels Zaccharias Glahn; Nielsen, Mogens Møller; Blagoev, Blagoy;

    2004-01-01

    -induced mitogenesis in cell lines. To further investigate the role of Odin in growth factor receptor signaling and to elucidate its biological function in vivo, we have generated mice deficient in Odin by gene targeting. Odin-deficient mice do not display any obvious phenotype, and histological examination...... of the kidney, lung and liver does not show any major abnormalities as compared to wild-type controls. However, mouse embryonic fibroblasts (MEFs) generated from Odin-deficient mice exhibit a hyperproliferative phenotype compared to wild-type-derived MEFs, consistent with its role as a negative regulator...

  7. Liver Disease and Pulmonary Hypertension

    Science.gov (United States)

    ... fats, produces several important com- pounds, stores certain vitamins, makes specific amino acids, converts glucose to glycogen, ... liver. This increased pres- sure causes blood to bypass the liver. As a result, the blood is ...

  8. Propylthiouracil for alcoholic liver disease

    DEFF Research Database (Denmark)

    Fede, Giuseppe; Germani, Giacomo; Gluud, Christian

    2011-01-01

    Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease.......Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease....

  9. Propylthiouracil for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2005-01-01

    Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease.......Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease....

  10. Takotsubo cardiomyopathy post liver transplantation.

    Science.gov (United States)

    Vachiat, Ahmed; McCutcheon, Keir; Mahomed, Adam; Schleicher, Gunter; Brand, Liezl; Botha, Jean; Sussman, Martin; Manga, Pravin

    2016-10-23

    A patient with end-stage liver disease developed stress-induced Takotsubo cardiomyopathy post liver transplantation, with haemodynamic instability requiring a left ventricular assist device. We discuss the diagnosis and management of this condition.

  11. Ton That Tung's livers.

    Science.gov (United States)

    Helling, Thomas S; Azoulay, Daniel

    2014-06-01

    Born in the early 20th century, the Vietnamese surgeon Ton That Tung received his medical education in French colonial Indochina at the fledgling l'Ecole de Médecine de Hanoi, the first indigenous medical school in Southeast Asia. The benefactor of a postgraduate position at the medical school, Ton That Tung subsequently obtained his surgical training at the Phù Doãn Hospital in Hanoi and concurrently developed a passion for the study of liver anatomy, pathology, and surgery. His contributions to an understanding of liver anatomy based on meticulous dissection of autopsy specimens antedated and rivaled later work by the famous Western anatomists Couinaud, Healey, Schroy, and others. Ton That Tung's contributions, however, were overshadowed by the intense national struggles of the Vietnamese to establish independent rule and self-governance from the French and by eventual alignment with eastern bloc Communist countries, thus isolating much of his work behind the "Iron Curtain" until well after the end of the Cold War. Nevertheless, Ton That Tung remains a pioneer in liver anatomy and liver surgery. His commitment to surgical science and, more importantly, to the Vietnamese people stands as a tribute to the tireless pursuit of his ideals.

  12. LIVER AND BILIARY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    12.1 Liver function2003091 Treatment of acute hepatic failure by transplantation of microencapsulated xenogenic hepatocyte.ZHANG Weijie(张伟杰), et al. Instit Organ Transplant, Tongji Hosp, Huazhong Univ Sci & Technol, Wuhan 430030. World Chin J Digestol 2002; 10 (12): 1396-1398.

  13. Nonalcoholic fatty liver disease

    DEFF Research Database (Denmark)

    Patrick-Melin, A J; Kalinski, M I; Kelly, K R

    2009-01-01

    that features steatosis plus inflammation, termed nonalcoholic steatohepatitis (NASH), which may in turn progress to hepatic fibrosis, cirrhosis, and sub-acute liver failure. Thus, NAFLD and its subsequent complications create a significant health burden, and currently there is no effective treatment strategy...

  14. Living Donor Liver Transplantation

    Science.gov (United States)

    ... be a husband or wife. What are Some Benefits of a Living-donor Liver Transplant? In the ... Not have a selfish motive for donating. Paid donation is illegal in the ... leave for being organ donors. Other employers have similar programs, so check ...

  15. Coffee and liver health.

    Science.gov (United States)

    Morisco, Filomena; Lembo, Vincenzo; Mazzone, Giovanna; Camera, Silvia; Caporaso, Nicola

    2014-01-01

    Coffee is one of the most widely used beverages in the world. It includes a wide array of components that can have potential implications for health. Several epidemiological studies associate coffee consumption with a reduced incidence of various chronic diseases such as diabetes, cardiovascular diseases, and neurodegenerative diseases. Over the past 20 years, an increasing number of epidemiological and experimental studies have demonstrated the positive effects of coffee on chronic liver diseases. Coffee consumption has been inversely associated with the activity of liver enzymes in subjects at risk, including heavy drinkers. Coffee favours an improvement in hepatic steatosis and fibrosis, and a reduction in cirrhosis and the risk of hepatocellular carcinoma. The mechanisms of action through which it exerts its beneficial effects are not fully understood. Experimental studies show that coffee consumption reduces fat accumulation and collagen deposition in the liver and promotes antioxidant capacity through an increase in glutathione as well as modulation of the gene and protein expression of several inflammatory mediators. Animal and in vitro studies indicate that cafestol and kahweol, 2 diterpens, can operate by modulating multiple enzymes involved in the detoxification process of carcinogens causing hepatocellular carcinoma. It is unclear whether the benefits are significant enough to "treat" patients with chronic liver disease. While we await clarification, moderate daily unsweetened coffee use is a reasonable adjuvant to therapy for these patients.

  16. Hypertension and liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2004-01-01

    Arterial hypertension is a common disorder with a frequency of 10% to 15% in subjects in the 40- to 60-year age group. Yet most reports find the prevalence of arterial hypertension in patients with chronic liver disease (cirrhosis) much lower. In this review, we consider the alterations in systemic...

  17. Cirrhosis of the liver

    DEFF Research Database (Denmark)

    Bendtsen, Flemming; Larsen, Fin Stolze; Ott, Peter

    2014-01-01

    Cirrhosis of the liver is a frequent and dangerous disease that causes numerous clinical contacts due to its complications. Competent and fast clinical decisions are often necessary in the acute setting and a broad clinical approach for the long-term problems due to the co-morbidity. Danish...

  18. Angiogenesis and liver fibrosis

    Institute of Scientific and Technical Information of China (English)

    Gülsüm ?zlem Elpek

    2015-01-01

    Recent data indicate that hepatic angiogenesis,regardless of the etiology, takes place in chronic liverdiseases (CLDs) that are characterized by inflammationand progressive fibrosis. Because antiangiogenictherapy has been found to be efficient inthe prevention of fibrosis in experimental models ofCLDs, it is suggested that blocking angiogenesis couldbe a promising therapeutic option in patients withadvanced fibrosis. Consequently, efforts are beingdirected to revealing the mechanisms involved inangiogenesis during the progression of liver fibrosis.Literature evidences indicate that hepatic angiogenesisand fibrosis are closely related in both clinical andexperimental conditions. Hypoxia is a major inducer ofangiogenesis together with inflammation and hepaticstellate cells. These profibrogenic cells stand at theintersection between inflammation, angiogenesis andfibrosis and play also a pivotal role in angiogenesis.This review mainly focuses to give a clear view on therelevant features that communicate angiogenesis withprogression of fibrosis in CLDs towards the-end point ofcirrhosis that may be translated into future therapies.The pathogenesis of hepatic angiogenesis associatedwith portal hypertension, viral hepatitis, non-alcoholicfatty liver disease and alcoholic liver disease are alsodiscussed to emphasize the various mechanisms involvedin angiogenesis during liver fibrogenesis.

  19. Radioembolization of liver tumors

    NARCIS (Netherlands)

    van den Hoven, AF

    2016-01-01

    Radioembolization is a therapy during which radioactive microspheres are administered through a microcatheter placed in the hepatic arterial vasculature in order to irradiate liver tumors from within. In the past decennium, this treatment has evolved as a safe and effective treatment option for pati

  20. Propylthiouracil for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2002-01-01

    Alcohol is the most common cause of liver disease in the Western world today. Randomised clinical trials have addressed the question whether propylthiouracil has any efficacy in patients with alcoholic liver disease.......Alcohol is the most common cause of liver disease in the Western world today. Randomised clinical trials have addressed the question whether propylthiouracil has any efficacy in patients with alcoholic liver disease....

  1. Bariatric Surgery and Liver Transplantation.

    Science.gov (United States)

    Suraweera, Duminda; Saab, Elena G; Choi, Gina; Saab, Sammy

    2017-03-01

    Obesity is an important public health and medical concern in the United States. The rate of obesity has steadily risen for the past several decades. Obesity is associated with the development of nonalcoholic steatohepatitis, which is one of the leading indications for liver transplantation. After liver transplantation, recipients tend to gain weight and develop recurrent fatty liver. Over time, recurrent fatty liver may impact patient and graft survival. A bariatric surgical approach may be beneficial in select patients.

  2. Egg phenotype differentiation in sympatric cuckoo Cuculus canorus gentes.

    Science.gov (United States)

    Antonov, Anton; Stokke, B G; Vikan, J R; Fossøy, F; Ranke, P S; Røskaft, E; Moksnes, A; Møller, A P; Shykoff, J A

    2010-06-01

    The brood parasitic common cuckoo Cuculus canorus consists of gentes, which typically parasitize only a single host species whose eggs they often mimic. Where multiple cuckoo gentes co-exist in sympatry, we may expect variable but generally poorer mimicry because of host switches or inter-gens gene flow via males if these also contribute to egg phenotypes. Here, we investigated egg trait differentiation and mimicry in three cuckoo gentes parasitizing great reed warblers Acrocephalus arundinaceus, marsh warblers Acrocephalus palustris and corn buntings Miliaria calandra breeding in close sympatry in partially overlapping habitat types. The three cuckoo gentes showed a remarkable degree of mimicry to their three host species in some but not all egg features, including egg size, a hitherto largely ignored feature of egg mimicry. Egg phenotype matching for both background and spot colours as well as for egg size has been maintained in close sympatry despite the possibility for gene flow.

  3. 25 Ways to Love Your Liver

    Science.gov (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  4. Effect of extracorporeal bioartificial liver support system on fulminant hepatic failure rabbits

    Institute of Scientific and Technical Information of China (English)

    Ying Jie Wang; Meng Dong Li; Yu Ming Wang; Guo Zheng Chen; Guo Dong Lu; Zao Xia Tan

    2000-01-01

    AIM To evaluate the possibility of using cultured human hepatocytes as a bridge between bioartificial liver and liver transplantation. METHODS In this experiment, the efficacy of extracorporeal bioartificial liver support system (EBLSS) consisting of spheriodal human liver cells and cultured hepatocytes supernatant was assessed in vivo using galactosamine induced rabbit model of fulminant hepatic failure. RiESULTS There was no difference of survival between the two groups of rabbits, but in the supported rabbits serum alanine aminotransferase, total bilirubin and creatinine were significantly lower and hepatocyte necrosis was markedly milder than those in control animals. In addition, a good viability of human liver cells was noted after the experiment. CONCLUSION EBLSS plays a biologic role in maintaining and compensating the function of the liver.

  5. A bioenergetics systems evaluation of ketogenic diet liver effects.

    Science.gov (United States)

    Hutfles, Lewis J; Wilkins, Heather M; Koppel, Scott J; Weidling, Ian W; Selfridge, J Eva; Tan, Eephie; Thyfault, John P; Slawson, Chad; Fenton, Aron W; Zhu, Hao; Swerdlow, Russell H

    2017-09-01

    Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body production. To further evaluate how ketogenic diets affect hepatocyte bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice maintained for 1 month on a ketogenic or standard chow diet. Compared with the standard diet, the ketogenic diet increased cytosolic and mitochondrial protein acetylation and also altered protein succinylation patterns. SIRT3 protein decreased while SIRT5 protein increased, and gluconeogenesis, oxidative phosphorylation, and mitochondrial biogenesis pathway proteins were variably and likely strategically altered. The pattern of changes observed can be used to inform a broader systems overview of how ketogenic diets affect liver bioenergetics.

  6. Gut-liver axis, nutrition, and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Kirpich, Irina A; Marsano, Luis S; McClain, Craig J

    2015-09-01

    Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases involving hepatic fat accumulation, inflammation with the potential progression to fibrosis and cirrhosis over time. NAFLD is often associated with obesity, insulin resistance, and diabetes. The interactions between the liver and the gut, the so-called "gut-liver axis", play a critical role in NAFLD onset and progression. Compelling evidence links the gut microbiome, intestinal barrier integrity, and NAFLD. The dietary factors may alter the gut microbiota and intestinal barrier function, favoring the occurrence of metabolic endotoxemia and low grade inflammation, thereby contributing to the development of obesity and obesity-associated fatty liver disease. Therapeutic manipulations with prebiotics and probiotics to modulate the gut microbiota and maintain intestinal barrier integrity are potential agents for NAFLD management. This review summarizes the current knowledge regarding the complex interplay between the gut microbiota, intestinal barrier, and dietary factors in NAFLD pathogenesis. The concepts addressed in this review have important clinical implications, although more work needs to be done to understand how dietary factors affect the gut barrier and microbiota, and to comprehend how microbe-derived components may interfere with the host's metabolism contributing to NAFLD development.

  7. Stem cells in liver disease

    NARCIS (Netherlands)

    Poll, D. van

    2008-01-01

    Failure of the liver, the largest vital organ in the body, unequivocally results in death. Hepatic failure most commonly evolves over a period of several years as a result of chronic liver disease, most often viral hepatitis or alcoholic liver damage. In rarer cases, the organ shuts down within

  8. [Local treatment of liver tumors

    DEFF Research Database (Denmark)

    Pless, T.K.; Skjoldbye, Bjørn Ole

    2008-01-01

    Local treatment of non-resectable liver tumors is common. This brief review describes the local treatment techniques used in Denmark. The techniques are evaluated according to the evidence in literature. The primary local treatment is Radiofrequency Ablation of both primary liver tumors and liver...

  9. Improved transvenous liver biopsy needle

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Matzen, P; Christoffersen, P

    1979-01-01

    A modified type of the standard transvenous cholangiography biopsy needle is described. The modified tranvenous liver biopsy needle caused only minimal artefactual changes of the liver biopsy specimens. The new type of biopsy needle is a modified Menghini needle. The conventional Menghini needle...... should be avoided for transvenous catheter biopsies because of risk of leaving catheter fragments in the liver....

  10. Pediatric obesity and the liver

    NARCIS (Netherlands)

    Koot, B.G.P.

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a frequent complication of obesity. In some of those with NAFLD, the fat accumulation in the liver will cause inflammation and fibrosis and can ultimately cause liver failure. In addition, in adults it has been established that NAFLD increases the risk of

  11. Stem cells in liver disease

    NARCIS (Netherlands)

    Poll, D. van

    2008-01-01

    Failure of the liver, the largest vital organ in the body, unequivocally results in death. Hepatic failure most commonly evolves over a period of several years as a result of chronic liver disease, most often viral hepatitis or alcoholic liver damage. In rarer cases, the organ shuts down within week

  12. Acute fatty liver in pregnancy.

    NARCIS (Netherlands)

    Tan, A.; Krieken, J.H.J.M. van; Peters, W.H.M.; Steegers, E.A.P.

    2002-01-01

    When confronted with liver abnormalities during the third trimester of pregnancy, one should consider acute fatty liver of pregnancy. The differential diagnosis with (pre-)eclampsia and HELLP syndrome is sometimes difficult. In these cases a liver biopsy is helpful though rarely performed during pre

  13. Systemic abnormalities in liver disease

    Institute of Scientific and Technical Information of China (English)

    Masami Minemura; Kazuto Tajiri; Yukihiro Shimizu

    2009-01-01

    Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases.

  14. Pediatric obesity and the liver

    NARCIS (Netherlands)

    Koot, B.G.P.

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a frequent complication of obesity. In some of those with NAFLD, the fat accumulation in the liver will cause inflammation and fibrosis and can ultimately cause liver failure. In addition, in adults it has been established that NAFLD increases the risk of

  15. Research Progress of Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    XU Lie-ming; JIA Ji-dong

    2005-01-01

    @@ Liver diseases are widespread in China.The disease mostly includes viral hepatitis,alcoholic or non alcoholic fatty degeneration or steatohepatitis, autoimmune liver disease,hepatic fibrosis/cirrhosis and hepatic cancer.The mechanism of most liver diseases was studied clearly in developed countries.

  16. Molecular Structure of Human-Liver Glycogen.

    Directory of Open Access Journals (Sweden)

    Bin Deng

    Full Text Available Glycogen is a highly branched glucose polymer which is involved in maintaining blood-sugar homeostasis. Liver glycogen contains large composite α particles made up of linked β particles. Previous studies have shown that the binding which links β particles into α particles is impaired in diabetic mice. The present study reports the first molecular structural characterization of human-liver glycogen from non-diabetic patients, using transmission electron microscopy for morphology and size-exclusion chromatography for the molecular size distribution; the latter is also studied as a function of time during acid hydrolysis in vitro, which is sensitive to certain structural features, particularly glycosidic vs. proteinaceous linkages. The results are compared with those seen in mice and pigs. The molecular structural change during acid hydrolysis is similar in each case, and indicates that the linkage of β into α particles is not glycosidic. This result, and the similar morphology in each case, together imply that human liver glycogen has similar molecular structure to those of mice and pigs. This knowledge will be useful for future diabetes drug targets.

  17. Molecular Structure of Human-Liver Glycogen

    Science.gov (United States)

    Deng, Bin; Sullivan, Mitchell A.; Chen, Cheng; Li, Jialun; Powell, Prudence O.; Hu, Zhenxia; Gilbert, Robert G.

    2016-01-01

    Glycogen is a highly branched glucose polymer which is involved in maintaining blood-sugar homeostasis. Liver glycogen contains large composite α particles made up of linked β particles. Previous studies have shown that the binding which links β particles into α particles is impaired in diabetic mice. The present study reports the first molecular structural characterization of human-liver glycogen from non-diabetic patients, using transmission electron microscopy for morphology and size-exclusion chromatography for the molecular size distribution; the latter is also studied as a function of time during acid hydrolysis in vitro, which is sensitive to certain structural features, particularly glycosidic vs. proteinaceous linkages. The results are compared with those seen in mice and pigs. The molecular structural change during acid hydrolysis is similar in each case, and indicates that the linkage of β into α particles is not glycosidic. This result, and the similar morphology in each case, together imply that human liver glycogen has similar molecular structure to those of mice and pigs. This knowledge will be useful for future diabetes drug targets. PMID:26934359

  18. RECG maintains plastid and mitochondrial genome stability by suppressing extensive recombination between short dispersed repeats.

    Directory of Open Access Journals (Sweden)

    Masaki Odahara

    2015-03-01

    Full Text Available Maintenance of plastid and mitochondrial genome stability is crucial for photosynthesis and respiration, respectively. Recently, we have reported that RECA1 maintains mitochondrial genome stability by suppressing gross rearrangements induced by aberrant recombination between short dispersed repeats in the moss Physcomitrella patens. In this study, we studied a newly identified P. patens homolog of bacterial RecG helicase, RECG, some of which is localized in both plastid and mitochondrial nucleoids. RECG partially complements recG deficiency in Escherichia coli cells. A knockout (KO mutation of RECG caused characteristic phenotypes including growth delay and developmental and mitochondrial defects, which are similar to those of the RECA1 KO mutant. The RECG KO cells showed heterogeneity in these phenotypes. Analyses of RECG KO plants showed that mitochondrial genome was destabilized due to a recombination between 8-79 bp repeats and the pattern of the recombination partly differed from that observed in the RECA1 KO mutants. The mitochondrial DNA (mtDNA instability was greater in severe phenotypic RECG KO cells than that in mild phenotypic ones. This result suggests that mitochondrial genomic instability is responsible for the defective phenotypes of RECG KO plants. Some of the induced recombination caused efficient genomic rearrangements in RECG KO mitochondria. Such loci were sometimes associated with a decrease in the levels of normal mtDNA and significant decrease in the number of transcripts derived from the loci. In addition, the RECG KO mutation caused remarkable plastid abnormalities and induced recombination between short repeats (12-63 bp in the plastid DNA. These results suggest that RECG plays a role in the maintenance of both plastid and mitochondrial genome stability by suppressing aberrant recombination between dispersed short repeats; this role is crucial for plastid and mitochondrial functions.

  19. A system to efficiently maintain embryonic lethal mutations in the flour beetle Tribolium castaneum.

    Science.gov (United States)

    Berghammer, A; Bucher, G; Maderspacher, F; Klingler, M

    1999-06-01

    Due to its small size, short life cycle, and easy maintenance, the flour beetle Tribolium castaneum is well suited for the genetic analysis of development. One drawback of Tribolium as a genetic system is, however, the difficulty of keeping embryonic lethal lines. Presently, only few lethal mutations can be kept as balanced stocks. Therefore, heterozygous carriers must be identified anew in every generation in order to maintain a recessive embryonic mutation. To alleviate this problem we have devised a block system that allows the simultaneous processing of many mutant lines or test crosses for visual inspection of larval cuticle phenotypes. Using this technique, one person can maintain about 100 embryonic lethal stocks, which makes feasible the thorough genetic analysis of embryogenesis in this species.

  20. Phenotypic deconstruction of gene circuitry.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  1. Phenotypic spectrum of GABRA1

    DEFF Research Database (Denmark)

    Johannesen, Katrine; Marini, Carla; Pfeffer, Siona

    2016-01-01

    myoclonic epilepsy (2), photosensitive idiopathic generalized epilepsy (1), and generalized epilepsy with febrile seizures plus (1) to severe epileptic encephalopathies (11). In the epileptic encephalopathy group, the patients had seizures beginning between the first day of life and 15 months, with a mean...... of 7 months. Predominant seizure types in all patients were tonic-clonic in 9 participants (56%) and myoclonic seizures in 5 (31%). EEG showed a generalized photoparoxysmal response in 6 patients (37%). Four selected mutations studied functionally revealed a loss of function, without a clear genotype......-phenotype correlation. CONCLUSIONS: GABRA1 mutations make a significant contribution to the genetic etiology of both benign and severe epilepsy syndromes. Myoclonic and tonic-clonic seizures with pathologic response to photic stimulation are common and shared features in both mild and severe phenotypes....

  2. Deciphering the Galaxy Guppy phenotype

    Directory of Open Access Journals (Sweden)

    Philip Shaddock

    2011-01-01

    Full Text Available Animal breeding hobbyists have been useful to science because they identify and isolate colorcoat mutations that geneticists can in turn use in their studies of the development and differentiation ofcolor cells. This paper discusses a very interesting color mutant, the Japanese Galaxy, tracing its creationfrom back to a self-educated genetics hobbyist, Hoskiki Tsutsui. The paper discusses a constituent genepreviously studied by Dr. Violet Phang, the snakeskin gene (the linked body and fin genes Ssb and Sst.And it discusses a gene previously unknown to science, the Schimmelpfennig Platinum gene (Sc.Through crossing experiments, the author determines that the combination of these two genes producesan intermediate phenotype, the Medusa. Incorporating the Grass (Gr, another gene unknown to sciencegene into the Medusa through a crossover produces the Galaxy phenotype. Microscope studies of thesnakeskin pattern in Galaxies and snakeskins reveals some parallels with similar studies made of theZebrafish Danio.

  3. Automated phenotyping of permanent crops

    Science.gov (United States)

    McPeek, K. Thomas; Steddom, Karl; Zamudio, Joseph; Pant, Paras; Mullenbach, Tyler

    2017-05-01

    AGERpoint is defining a new technology space for the growers' industry by introducing novel applications for sensor technology and data analysis to growers of permanent crops. Serving data to a state-of-the-art analytics engine from a cutting edge sensor platform, a new paradigm in precision agriculture is being developed that allows growers to understand the unique needs of each tree, bush or vine in their operation. Autonomous aerial and terrestrial vehicles equipped with multiple varieties of remote sensing technologies give AGERpoint the ability to measure key morphological and spectral features of permanent crops. This work demonstrates how such phenotypic measurements combined with machine learning algorithms can be used to determine the variety of crops (e.g., almond and pecan trees). This phenotypic and varietal information represents the first step in enabling growers with the ability to tailor their management practices to individual plants and maximize their economic productivity.

  4. Experimental study of bioartificial liver with cultured human liver cells

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    AIM To establish an extracorporeal bioartificial liver support system (EBLSS) using cultured human liver cells and to study its support effect for fulminant hepatic failure (FHF).METHODS The liver support experiment of EBLSS consisting of aggregates cultured human liver cells, hollow fiber bioreactor, and circulation unit was carried out in dizhepatic dogs.RESULTS The viability of isolated hepatocytes and nonparenchymal liver cells reached 96%. These cells were successfully cultured as multicellular spheroids with synthetic technique. The typical morphological appearance was retained up to the end of the artificial liver experiment. Compared with the control dogs treated with EBLSS without liver cells, the survival time of artificial liver support dogs was significantly prolonged. The changes of blood pressure, heart rate and ECG were slow. Both serum ammonia and lactate levels were significantly lowered at the 3rd h and 5th h. In addition, a good viability of human liver cells was noted after 5 h experiment.CONCLUSION EBLSS playing a metabolic role of cultured human hepatocytes, is capable of compensating the function of the liver, and could provide effective artificial liver support and therapy for patients with FHF.

  5. Wine Expertise Predicts Taste Phenotype.

    Science.gov (United States)

    Hayes, John E; Pickering, Gary J

    2012-03-01

    Taste phenotypes have long been studied in relation to alcohol intake, dependence, and family history, with contradictory findings. However, on balance - with appropriate caveats about populations tested, outcomes measured and psychophysical methods used - an association between variation in taste responsiveness and some alcohol behaviors is supported. Recent work suggests super-tasting (operationalized via propylthiouracil (PROP) bitterness) not only associates with heightened response but also with more acute discrimination between stimuli. Here, we explore relationships between food and beverage adventurousness and taste phenotype. A convenience sample of wine drinkers (n=330) were recruited in Ontario and phenotyped for PROP bitterness via filter paper disk. They also filled out a short questionnaire regarding willingness to try new foods, alcoholic beverages and wines as well as level of wine involvement, which was used to classify them as a wine expert (n=110) or wine consumer (n=220). In univariate logisitic models, food adventurousness predicted trying new wines and beverages but not expertise. Likewise, wine expertise predicted willingness to try new wines and beverages but not foods. In separate multivariate logistic models, willingness to try new wines and beverages was predicted by expertise and food adventurousness but not PROP. However, mean PROP bitterness was higher among wine experts than wine consumers, and the conditional distribution functions differed between experts and consumers. In contrast, PROP means and distributions did not differ with food adventurousness. These data suggest individuals may self-select for specific professions based on sensory ability (i.e., an active gene-environment correlation) but phenotype does not explain willingness to try new stimuli.

  6. Phenotyping jasmonate regulation of senescence.

    Science.gov (United States)

    Seltmann, Martin A; Berger, Susanne

    2013-01-01

    Osmotic stress induces several senescence-like processes in leaves, such as specific changes in gene expression and yellowing. These processes are dependent on the accumulation of jasmonates and on intact jasmonate signaling. This chapter describes the treatment of Arabidopsis thaliana leaves with sorbitol as an osmotic stress agent and the determination of the elicited phenotypes encompassing chlorophyll loss, degradation of plastidial membrane lipids, and induction of genes regulated by senescence and jasmonate.

  7. Statistical models for trisomic phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Lamb, N.E.; Sherman, S.L.; Feingold, E. [Emory Univ., Atlanta, GA (United States)

    1996-01-01

    Certain genetic disorders are rare in the general population but more common in individuals with specific trisomies, which suggests that the genes involved in the etiology of these disorders may be located on the trisomic chromosome. As with all aneuploid syndromes, however, a considerable degree of variation exists within each phenotype so that any given trait is present only among a subset of the trisomic population. We have previously presented a simple gene-dosage model to explain this phenotypic variation and developed a strategy to map genes for such traits. The mapping strategy does not depend on the simple model but works in theory under any model that predicts that affected individuals have an increased likelihood of disomic homozygosity at the trait locus. This paper explores the robustness of our mapping method by investigating what kinds of models give an expected increase in disomic homozygosity. We describe a number of basic statistical models for trisomic phenotypes. Some of these are logical extensions of standard models for disomic phenotypes, and some are more specific to trisomy. Where possible, we discuss genetic mechanisms applicable to each model. We investigate which models and which parameter values give an expected increase in disomic homozygosity in individuals with the trait. Finally, we determine the sample sizes required to identify the increased disomic homozygosity under each model. Most of the models we explore yield detectable increases in disomic homozygosity for some reasonable range of parameter values, usually corresponding to smaller trait frequencies. It therefore appears that our mapping method should be effective for a wide variety of moderately infrequent traits, even though the exact mode of inheritance is unlikely to be known. 21 refs., 8 figs., 1 tab.

  8. The inverse relationship between bladder and liver in 4-aminobiphenyl-induced DNA damage.

    Science.gov (United States)

    Bhattacharya, Arup; Klaene, Joshua J; Li, Yun; Paonessa, Joseph D; Stablewski, Aimee B; Vouros, Paul; Zhang, Yuesheng

    2015-01-20

    Bladder cancer risk is significantly higher in men than in women. 4-Aminobiphenyl (ABP) is a major human bladder carcinogen from tobacco smoke and other sources. In mice, male bladder is more susceptible to ABP-induced carcinogenesis than female bladder, but ABP is more carcinogenic in the livers of female mice than of male mice. Here, we show that castration causes male mice to acquire female phenotype regarding susceptibility of bladder and liver to ABP. However, spaying has little impact on organ susceptibility to ABP. Liver UDP-glucuronosyltransferases (UGTs) are believed to protect liver against but sensitize bladder to ABP, as glucuronidation of ABP and its metabolites generally reduces their toxicity and promotes their elimination via urine, but the metabolites are labile in urine, delivering carcinogenic species to the bladder. Indeed, liver expression of ABP-metabolizing human UGT1A3 transgene in mice increases bladder susceptibility to ABP. However, ABP-specific liver UGT activity is significantly higher in wild-type female mice than in their male counterparts, and castration also significantly increases ABP-specific UGT activity in the liver. Taken together, our data suggest that androgen increases bladder susceptibility to ABP via liver, likely by modulating an ABP-metabolizing liver enzyme, but exclude UGT as an important mediator.

  9. Lin28 and let-7: roles and regulation in liver diseases.

    Science.gov (United States)

    McDaniel, Kelly; Hall, Chad; Sato, Keisaku; Lairmore, Terry; Marzioni, Marco; Glaser, Shannon; Meng, Fanyin; Alpini, Gianfranco

    2016-05-15

    The diagnosis and treatment of liver disease remain a major health concern worldwide because of the diverse etiologies of this disease. For this reason, new therapeutic targets are greatly needed to halt the progression of this damaging disease. Upon initiation of liver injury by viral infection, autoimmune disease or toxin, and/or hepatitis, chronic disease may develop, which can progress to cirrhosis, hepatocellular carcinoma (HCC), cholangiocarcinoma, liver failure, or death. The Lin28/lethal-7 (let-7) molecular switch has emerged as a central regulator of multiorgan injuries and cancer development. Lin28 is a stem cell marker vital to initiation or maintenance of a stem cell phenotype. Lin28 has not been extensively studied in the liver, despite its ability to induce tissue regeneration via reprogramming of oxidative enzymes in other tissues and its involvement with numerous upstream regulators and downstream targets in liver disease. Theoretically, overexpression of Lin28 in certain forms of liver disease could be a potential treatment that aids in liver regeneration. Alternatively, Lin28 has been implicated numerous times in the progression of diverse cancer types and is associated with increased severity of disease. In this case, Lin28 could be a potential inhibitory target to prevent malignant transformation in the liver. This review seeks to characterize the role of Lin28 in liver disease.

  10. Transcriptional changes are involved in phenotype switching in Streptococcus equi subspecies equi.

    Science.gov (United States)

    Steward, Karen F; Robinson, Carl; Waller, Andrew S

    2016-04-01

    Phenotypic heterogeneity within a population of bacteria, through genetic or transcriptional variation, enables survival and persistence in challenging and changing environments. We report here that a recent clinical isolate of S. equi, strain 1691 (Se1691), yielded a mixture of reduced capsule and mucoid colonies on primary isolation when grown on colistin-oxolinic acid blood agar (COBA) streptococcal selective plates. Passaging colonies of Se1691, with a reduced capsule phenotype maintained this mixed phenotype. In contrast, passaging mucoid colonies fixed the mucoid phenotype, suggesting adaptive genetic or transcriptional changes in response to growth on artificial media. However, despite obvious phenotypic and transcriptional differences, there were no apparent differences in the genome sequences of Se1691 recovered from colonies with a mucoid or reduced capsule phenotype. We identified 105 differentially transcribed genes in the transcriptomes of reduced capsule and mucoid colonies. The reduced capsule phenotype was associated with a significant reduction in transcription of the has locus (SEQ_0269 Q = 0.0015, SEQ_0270 Q = 0.0015, SEQ_0271 Q = 0.0285) and the amount of hyaluronic acid on the surface of S. equi recovered from non-mucoid colonies (P = 0.017). Significant differences in the transcription of 21 surface and secreted proteins were also observed. Our data show that changes in the bacterial transcriptome are linked to the mixed colony phenotype of Se1691.

  11. Environmental Fluctuations and Their Consequences for the Evolution of Phenotypic Diversity

    Directory of Open Access Journals (Sweden)

    Miguel A. Fuentes

    2017-05-01

    Full Text Available An essential aspect of the current theory of adaptive speciation is the maintenance of phenotypic variation and the evolution of stationary stable phenotypic diversity, a phenomenon known as evolutionary branching. Theoretical and empirical evidence suggest that phenotypic variation can be maintained by favoring rare phenotypes, for example, through frequency-dependent selection. However, even when phenotypic variation is provided, the conditions leading to evolutionary branching are not universal. In order to lead to stable diversification, current models of adaptive speciation, such as the Lotka-Volterra competition model, must resort to strong assumptions that range from using unrealistic shape parameters for the competition and carrying capacity functions, modeling separately the generation of discontinuities in niche space, to increasing the dimensionality of phenotypic traits. Here, we introduce a stochastic version of the Lotka-Volterra competition model. We demonstrate that environmental fluctuations suffice to lead consistently to phenotypic diversification and evolutionary branching. Our observations build upon previous findings identifying a role for stochastic fluctuations on the evolution of phenotypic diversity, emphasize the difference between strong vs. weak assumptions in the stability of the LVC model, and suggest that the conditions for evolutionary branching are more relaxed than anticipated.

  12. Environmental fluctuations and their consequences for the evolution of phenotypic diversity

    Science.gov (United States)

    Fuentes, Miguel A.; Ferrada, Evandro

    2017-05-01

    An essential aspect of the current theory of adaptive speciation is the maintenance of phenotypic variation and the evolution of stationary stable phenotypic diversity, a phenomenon known as evolutionary branching. Theoretical and empirical evidence suggest that phenotypic variation can be maintained by favoring rare phenotypes, for example, through frequency-dependent selection. However, even when phenotypic variation is provided, the conditions leading to evolutionary branching are not universal. In order to lead to stable diversification, current models of adaptive speciation, such as the Lotka-Volterra competition model, must resort to strong assumptions that range from using unrealistic shape parameters for the competition and carrying capacity functions, modeling separately the generation of discontinuities in niche space, to increasing the dimensionality of phenotypic traits. Here, we introduce a stochastic version of the Lotka-Volterra competition model. We demonstrate that environmental fluctuations suffice to lead consistently to phenotypic diversification and evolutionary branching. Our observations build upon previous findings identifying a role for stochastic fluctuations on the evolution of phenotypic diversity, emphasize the difference between strong versus weak assumptions in the stability of the LVC model, and suggest that the conditions for evolutionary branching are more relaxed than anticipated.

  13. Cryopreservation Maintains Functionality of Human iPSC Dopamine Neurons and Rescues Parkinsonian Phenotypes In Vivo

    Directory of Open Access Journals (Sweden)

    Dustin R. Wakeman

    2017-07-01

    Full Text Available A major challenge for clinical application of pluripotent stem cell therapy for Parkinson's disease (PD is large-scale manufacturing and cryopreservation of neurons that can be efficiently prepared with minimal manipulation. To address this obstacle, midbrain dopamine neurons were derived from human induced pluripotent stem cells (iPSC-mDA and cryopreserved in large production lots for biochemical and transplantation studies. Cryopreserved, post-mitotic iPSC-mDA neurons retained high viability with gene, protein, and electrophysiological signatures consistent with midbrain floor-plate lineage. To test therapeutic efficacy, cryopreserved iPSC-mDA neurons were transplanted without subculturing into the 6-OHDA-lesioned rat and MPTP-lesioned non-human-primate models of PD. Grafted neurons retained midbrain lineage with extensive fiber innervation in both rodents and monkeys. Behavioral assessment in 6-OHDA-lesioned rats demonstrated significant reversal in functional deficits up to 6 months post transplantation with reinnervation of the host striatum and no aberrant growth, supporting the translational development of pluripotent cell-based therapies in PD.

  14. In situ characterization of intrahepatic non-parenchymal cells in PSC reveals phenotypic patterns associated with disease severity.

    Science.gov (United States)

    Berglin, Lena; Bergquist, Annika; Johansson, Helene; Glaumann, Hans; Jorns, Carl; Lunemann, Sebastian; Wedemeyer, Heiner; Ellis, Ewa C; Björkström, Niklas K

    2014-01-01

    Liver-infiltrating T cells have been implicated in the pathogenesis of primary sclerosing cholangitis (PSC), however little information is available about changes in other cellular compartments in the liver during PSC. This study aimed to characterize non-parenchymal intrahepatic cells in PSC livers and to find associations between phenotypes and disease severity. Using immunohistochemistry, followed by automated image analysis and quantification and a principal component analysis, we have studied non-parenchymal intrahepatic cells in PSC-patient livers (n = 17) and controls (n = 17). We observed a significant increase of T cells in the PSC patients, localized to the fibrotic areas. MAIT cells, normally present at high numbers in the liver, were not increased to the same extent. PSC patients had lower expression of MHC class I than controls. However, the levels of NKp46+ NK cells were similar between patients and controls, nevertheless, NKp46 was identified as a phenotypic marker that distinguished PSC patients with mild from those with severe fibrosis. Beyond that, a group of PSC patients had lost expression of Caldesmon and this was associated with more extensive bile duct proliferation and higher numbers of T cells. Our data reveals phenotypic patterns in PSC patients associated with disease severity.

  15. In situ characterization of intrahepatic non-parenchymal cells in PSC reveals phenotypic patterns associated with disease severity.

    Directory of Open Access Journals (Sweden)

    Lena Berglin

    Full Text Available Liver-infiltrating T cells have been implicated in the pathogenesis of primary sclerosing cholangitis (PSC, however little information is available about changes in other cellular compartments in the liver during PSC. This study aimed to characterize non-parenchymal intrahepatic cells in PSC livers and to find associations between phenotypes and disease severity. Using immunohistochemistry, followed by automated image analysis and quantification and a principal component analysis, we have studied non-parenchymal intrahepatic cells in PSC-patient livers (n = 17 and controls (n = 17. We observed a significant increase of T cells in the PSC patients, localized to the fibrotic areas. MAIT cells, normally present at high numbers in the liver, were not increased to the same extent. PSC patients had lower expression of MHC class I than controls. However, the levels of NKp46+ NK cells were similar between patients and controls, nevertheless, NKp46 was identified as a phenotypic marker that distinguished PSC patients with mild from those with severe fibrosis. Beyond that, a group of PSC patients had lost expression of Caldesmon and this was associated with more extensive bile duct proliferation and higher numbers of T cells. Our data reveals phenotypic patterns in PSC patients associated with disease severity.

  16. Genetic background of phenotypic variation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A noteworthy feature of the living world is its bewildering variability. A key issue in several biological disciplines is the achievement of an understanding of the hereditary basis of this variability. Two opposing, but not necessarily irreconcilable conceptions attempt to explain the underlying mechanism. The gene function paradigm postulates that phenotypic variance is generated by the polymorphism in the coding sequences of genes. However, comparisons of a great number of homologous gene and protein sequences have revealed that they predominantly remained functionally conserved even across distantly related phylogenic taxa. Alternatively, the gene regulation paradigm assumes that differences in the cis-regulatory region of genes do account for phenotype variation within species. An extension of this latter concept is that phenotypic variability is generated by the polyrnorphism in the overall gene expression profiles of gene networks.In other words, the activity of a particular gene is a system property determined both by the cis-regulatory sequences of the given genes and by the other genes of a gene network, whose expressions vary among individuals, too. Novel proponents of gene function paradigm claim that functional genetic variance within the coding sequences of regulatory genes is critical for the generation of morphological polymorphism. Note, however, that these developmental genes play direct regulatory roles in the control of gene expression.

  17. Phenotypic covariance at species’ borders

    Science.gov (United States)

    2013-01-01

    Background Understanding the evolution of species limits is important in ecology, evolution, and conservation biology. Despite its likely importance in the evolution of these limits, little is known about phenotypic covariance in geographically marginal populations, and the degree to which it constrains, or facilitates, responses to selection. We investigated phenotypic covariance in morphological traits at species’ borders by comparing phenotypic covariance matrices (P), including the degree of shared structure, the distribution of strengths of pair-wise correlations between traits, the degree of morphological integration of traits, and the ranks of matricies, between central and marginal populations of three species-pairs of coral reef fishes. Results Greater structural differences in P were observed between populations close to range margins and conspecific populations toward range centres, than between pairs of conspecific populations that were both more centrally located within their ranges. Approximately 80% of all pair-wise trait correlations within populations were greater in the north, but these differences were unrelated to the position of the sampled population with respect to the geographic range of the species. Conclusions Neither the degree of morphological integration, nor ranks of P, indicated greater evolutionary constraint at range edges. Characteristics of P observed here provide no support for constraint contributing to the formation of these species’ borders, but may instead reflect structural change in P caused by selection or drift, and their potential to evolve in the future. PMID:23714580

  18. Adaptive evolution of molecular phenotypes

    Science.gov (United States)

    Held, Torsten; Nourmohammad, Armita; Lässig, Michael

    2014-09-01

    Molecular phenotypes link genomic information with organismic functions, fitness, and evolution. Quantitative traits are complex phenotypes that depend on multiple genomic loci. In this paper, we study the adaptive evolution of a quantitative trait under time-dependent selection, which arises from environmental changes or through fitness interactions with other co-evolving phenotypes. We analyze a model of trait evolution under mutations and genetic drift in a single-peak fitness seascape. The fitness peak performs a constrained random walk in the trait amplitude, which determines the time-dependent trait optimum in a given population. We derive analytical expressions for the distribution of the time-dependent trait divergence between populations and of the trait diversity within populations. Based on this solution, we develop a method to infer adaptive evolution of quantitative traits. Specifically, we show that the ratio of the average trait divergence and the diversity is a universal function of evolutionary time, which predicts the stabilizing strength and the driving rate of the fitness seascape. From an information-theoretic point of view, this function measures the macro-evolutionary entropy in a population ensemble, which determines the predictability of the evolutionary process. Our solution also quantifies two key characteristics of adapting populations: the cumulative fitness flux, which measures the total amount of adaptation, and the adaptive load, which is the fitness cost due to a population's lag behind the fitness peak.

  19. Functions of autophagy in normal and diseased liver

    Science.gov (United States)

    Czaja, Mark J.; Ding, Wen-Xing; Donohue, Terrence M.; Friedman, Scott L.; Kim, Jae-Sung; Komatsu, Masaaki; Lemasters, John J.; Lemoine, Antoinette; Lin, Jiandie D.; Ou, Jing-hsiung James; Perlmutter, David H.; Randall, Glenn; Ray, Ratna B.; Tsung, Allan; Yin, Xiao-Ming

    2013-01-01

    Autophagy has emerged as a critical lysosomal pathway that maintains cell function and survival through the degradation of cellular components such as organelles and proteins. Investigations specifically employing the liver or hepatocytes as experimental models have contributed significantly to our current knowledge of autophagic regulation and function. The diverse cellular functions of autophagy, along with unique features of the liver and its principal cell type the hepatocyte, suggest that the liver is highly dependent on autophagy for both normal function and to prevent the development of disease states. However, instances have also been identified in which autophagy promotes pathological changes such as the development of hepatic fibrosis. Considerable evidence has accumulated that alterations in autophagy are an underlying mechanism of a number of common hepatic diseases including toxin-, drug- and ischemia/reperfusion-induced liver injury, fatty liver, viral hepatitis and hepatocellular carcinoma. This review summarizes recent advances in understanding the roles that autophagy plays in normal hepatic physiology and pathophysiology with the intent of furthering the development of autophagy-based therapies for human liver diseases. PMID:23774882

  20. Medicinal chemistry design principles for liver targeting through OATP transporters.

    Science.gov (United States)

    Tu, Meihua; Mathiowetz, Alan M; Pfefferkorn, Jeffrey A; Cameron, Kimberly O; Dow, Robert L; Litchfield, John; Di, Li; Feng, Bo; Liras, Spiros

    2013-01-01

    The tissue distribution of a drug can have significant impact on both its efficacy and safety. As a consequence, selective tissue targeting has become an attractive approach for optimizing the window between efficacy and safety for drug targets that are ubiquitously expressed and important in key physiological processes. Given the liver's key role in metabolic regulation and the fact that it is the principal tissue affected by diseases such as hepatitis B and C viruses as well as hepatocellular carcinoma, designing drugs with hepatoselective distribution profiles is an important strategy in developing safe cardiovascular, metabolic, antiviral and oncology drug candidates. In this paper, we analyze a diverse set of compounds from four different projects within Pfizer that specifically pursued liver targeting strategies. A number of key in vitro and in vivo ADME endpoints were collected including in vivo tissue exposure, oral bioavailability, clearance in preclinical species and in vitro hepatic OATP uptake, in vitro rat liver microsomal stability, permeability, solubility, logD, and others. From this analysis, we determined a set of general structure-liver-selectivity guides for designing orally bioavailable, liver-targeted candidates using liver specific OATP transporters. The guidelines have been formulated using straightforward molecular descriptors and in vitro properties that medicinal chemists routinely optimize. Our analysis emphasizes the need to focus on a chemical space with balanced lipophilicity, high aqueous solubility and low passive permeability in order to achieve the desired hepatoselectivity while maintaining fraction absorbed.